PMID- 1733543 TI - Intrapleural epidural catheter for the treatment of pneumothorax. PMID- 1733544 TI - Obstetrical anaesthesia for patients with HELLP syndrome. PMID- 1733545 TI - SIADH following minor surgery. PMID- 1733546 TI - Fibreoptic bronchoscopic intubation after induction of general anaesthesia: another approach. PMID- 1733547 TI - Hyperthermia after cardiopulmonary bypass in a child. PMID- 1733548 TI - Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside. AB - Cytosine arabinoside (ara-C) and uracil arabinoside (ara-U) levels were measured in the plasma, cerebrospinal fluid (CSF), and urine of 10 patients exhibiting primary central nervous system lymphoma who received 31 infusions of high-dose ara-C (3 g/m2) as part of their treatment regimen. Peak plasma and CSF ara-C levels were 10.8 and 1.5 micrograms/ml, respectively. Ara-C was cleared more rapidly from plasma than from CSF. Ara-U appeared rapidly in both plasma and CSF, reaching a peak that was 10 times higher than the corresponding ara-C concentration (104 and 11.2 micrograms/ml, respectively). Only 4%-6% of the dose was excreted unchanged in the urine, but 63%-73% of it appeared as ara-U within the first 24 h. The presence of leptomeningeal lymphoma did not affect the CSF level of ara-C or ara-U. PMID- 1733549 TI - 5-Fluorouracil, leucovorin, hydroxyurea, and escalating doses of continuous infusion cisplatin with concomitant radiotherapy: a clinical and pharmacologic study. AB - Cisplatin (CDDP), 5-fluorouracil (5-FU), and hydroxyurea (HU) have individually demonstrated activity against several solid tumors, act synergistically with each other in vitro, and may act as radiation sensitizers. Therefore, we designed a phase I study to determine the maximally tolerated dose of cisplatin as given in addition to our previously described combination of 5-FU, HU, and concomitant radiotherapy (XRT). Patients exhibiting advanced solid tumors requiring palliative XRT were eligible. The regimen consisted of 1 g HU given p.o.b.i.d. on days 1-5, 600 mg/m2 5-FU given i.v. daily by continuous infusion (c.i.) on days 1 5, escalating doses of cisplatin starting at 10 mg/m2 daily given by c.i. on days 1-5, and involved-field XRT carried out on days 1-5. The cycle was repeated every 14 days until the target XRT dose had been reached. In all, 19 patients were entered at the first dose level, and cumulative grade 3-4 myelosuppression was seen in 16 subjects. As no dose escalation was feasible, the chemotherapy was subsequently altered by using the above regimen for cycles 1, 3, 5, and 7 and substituting the less myelosuppressive regimen of 1 g HU given p.o.b.i.d. on days 1-5, 400 mg/m2 5-FU given i.v. daily by c.i., and 100 mg leucovorin given p.o.4 h on days 1-5 for cycles 2, 4, and 6. On this alternating program, 28 patients were treated with escalating doses of CDDP. The dose-limiting toxicity was again myelosuppression, which was prohibitive at a CDDP dose of 20 mg/m2 daily. In the final phase of the protocol, 30 subjects were treated with the above alternating cycle regimen at a CDDP dose of 20 mg/m2 daily and a decreased HU dose of 500 mg p.o.b.i.d. in an attempt to circumvent the myelosuppression associated with this dose of CDDP. Although severe acute toxicity (cycles 1 and 2) was observed less frequently, cumulative toxicity (all cycles) remained pronounced. The other major toxicity encountered was mucositis, which was particularly pronounced in patients receiving radiation to the head and neck and following leucovorin-containing cycles. Plasma concentrations of free platinum did not correlate with the CDDP dose, possibly due to the narrow range of doses given. Pharmacodynamic modeling demonstrated that the CDDP dose and the HU dose were associated with leukopenia. Antitumor activity was demonstrated in a number of solid tumors particularly non small-cell lung cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1733550 TI - In vitro succinate dehydrogenase chemosensitivity of gastric carcinoma- relationship to DNA content. AB - Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was microspectrophotometrically determined. Following exposure of malignant tissue to carboquone (CQ) and cisplatin (DDP), the mean SD activity in cells displaying a relatively regular DNA distribution (type II) was significantly higher than that in those exhibiting a widely scattered DNA distribution (type IV; P less than 0.01 in CQ, P less than 0.05 in DDP). A similar tendency was recognized in cells that were treated with aclacinomycin A (ACR), Adriamycin (ADM), and mitomycin C (MMC). Such a decrease in SD activity in cells exhibiting a type IV pattern was remarkable, especially in cases undifferentiated adenocarcinoma. Mitotic counting analysis revealed a significantly higher value for DNA pattern type IV as compared with the findings for type II (P less than 0.01). These results demonstrate that gastric carcinoma displaying a high malignant potentially shows a better response to antitumor drugs. Adjuvant chemotherapy prescribed following drug-sensitivity testing should be effective against such tumors. PMID- 1733551 TI - Antitumor drug cross-resistance in vivo in a murine P388 leukemia resistant to ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7 - ylcarbamate 2 hydroxyethanesulfonate hydrate (NSC 370,147) 370147. AB - Ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7- ylcarbamate 2 hydroxyethane-sulfonate hydrate (NSC 370147) is a potent mitotic inhibitor, which has provided the basis for a candidate for clinical trial. As observed with clinically useful drugs, the development of clinical resistance to NSC 370147 will probably be encountered. Information concerning resistance to NSC 370147 should aid in the design of strategies for the optimal clinical use of the drug. A P388 leukemia resistant to NSC 370147 (P388/NSC 370147) was isolated and its in vivo cross-resistance profile was determined. The P388/NSC 370147 line was cross resistant to vincristine but was not cross-resistant to doxorubicin, etoposide, cisplatin, melphalan, methotrexate, or 5-fluorouracil. This information plus other in vivo cross-resistance data [Waud et al. (1990) Cancer Res 50: 3239] suggests that NSC 370147 may be useful in non-cross-resistant combinations with doxorubicin, melphalan, cisplatin, or methotrexate. The lack of cross-resistance of P388/NSC 370147 to doxorubicin and etoposide shows that resistance to NSC 370147 does not involve multidrug resistance and suggests that the mdr1 gene is not involved in resistance to NSC 370147. PMID- 1733552 TI - A clinical and pharmacological study of high-dose mitozolomide given in conjunction with autologous bone marrow rescue. AB - In conjunction with autologous bone marrow rescue, high-dose mitozolomide was given i.v. to 16 patients with refractory malignancies at doses ranging from 100 to 400 mg/m2 over 1 h. Neutropaenia occurred consistently at 300 mg/m2, and three trivial infective episodes were recorded. Thrombocytopaenia occurred consistently at 150 mg/m2, and three patients experienced episodes of minor bleeding. The death of one subject was attributable to pulmonary thromboembolism during the bone marrow reinfusion. Transient emesis and mild alopecia were the only other toxicities. Three of six evaluable patients receiving greater than or equal to 300 mg/m2 exhibited measurable reductions in tumour dimensions, although these failed to fulfil the criteria for a partial response. Mitozolomide was undetectable in plasma at 12 h after drug administration. The plasma pharmacokinetic data fitted mono- or biexponential models in all patients. Model independent pharmacokinetic parameters were: peak plasma drug concentration, 3.4 46 mg/l; AUC, 8-82 mg h l-1; clearance, 7.6-45 l/h; steady-state volume of distribution, 11-85 l; and plasma elimination half-life, 1.4-2.8 h. Dose dependent pharmacokinetics were not observed, and only a small percentage of the delivered dose was eliminated unchanged in the urine. The maximally tolerated dose of mitozolomide given with autologous bone marrow rescue was greater than 400 mg/m2. At this dose myelosuppression was the only major toxicity, and the plasma drug levels and AUC values were comparable to those obtained after therapeutic doses in experimental models. PMID- 1733553 TI - Beta-carotene and/or vitamin E as modulators of alkylating agents in SCC-25 human squamous carcinoma cells. AB - Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo. PMID- 1733554 TI - Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors. AB - Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastrointestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors. PMID- 1733556 TI - Effects of carboplatin on the testis. A histological study. AB - In the present study, the influence of carboplatin [diammine(cyclobutane-1,1 dicarboxylato)platinum(II)], the main and most active representative of second generation antitumour platinum complexes, on the morphology of the testes of male CF1 mice was investigated histologically by examining semithick sections. Carboplatin was administered in doses of 30, 60, or 120 mg/kg and applied as a single intraperitoneal injection. For comparison purposes, the parent compound cisplatin [cis-diamminedichloroplatinum(II)] was administered at equitoxic doses (3, 6 or 12 mg/kg). At various intervals between days 1 and 28 after treatment, the testes were removed and embedded in Epon. Both compounds effected severe structural alterations of Sertoli cells, disrupted the blood/testis barrier, and impaired the processes both of spermatogenesis and spermiohistogenesis. The structural damage in the testes following treatment with carboplatin was at least as pronounced as that occurring under the influence of equitoxic doses of cisplatin. Within a few days, the intercellular spaces around Sertoli cells widened, the tight contacts with neighbouring cells were disrupted, the cytoplasm of Sertoli cells disintegrated and their nuclei shrank. Numerous necroses, abnormal mitotic figures of spermatogenic cells and malformed spermatozoa appeared. Severe damage was evident on days 10-21 after treatment with carboplatin, the strength of the symptoms being clearly dependent on the dose applied. The first indications of ongoing recovery processes were detected on day 21 in the case of the low dose (30 mg/kg) or on day 28 following treatment with 60 mg/kg or 120 mg/kg. These results confirm that carboplatin is at least as toxic to the testes as cisplatin and that its substitution for cisplatin in clinical therapy does not diminish the problem of drug-induced infertility following platinum-based chemotherapy. PMID- 1733555 TI - Experimental basis for increasing the therapeutic index of cis diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high zinc diet. AB - Metallothionein (MT), a ubiquitous intracellular protein, confers resistance to the toxic effects of platinum compounds. Since a high-zinc diet has been shown to induce MT synthesis in extracerebral tissues but not in brain, we investigated whether it could provide an experimental basis for decreasing the hematotoxicity of carboplatin without impairing its activity against brain tumors. After 2 weeks on either a high-zinc diet or a control diet (zinc content, 180 vs 10 ppm), mice and rats received various doses of carboplatin or Hanks' balanced salt solution by i.p. injection. The hematotoxicity of carboplatin was evaluated with an assay of colony-forming units of granulocytes and mononuclear cells in mice. The high zinc diet enabled a 50% increase in the carboplatin dose without increasing hematotoxicity. The antitumor activity was evaluated with an assay of the colony forming efficiency of gliosarcoma cells from 9L brain tumors in rats. The high zinc diet did not alter the efficacy of carboplatin against this brain tumor. Northern blot analysis confirmed that the high-zinc diet induced MT mRNA in the kidney but not in the brain of mice and rats; it also showed MT mRNA induction in bone marrow cells of mice but not in rat 9L brain tumors. These results suggest that increasing the dietary intake of zinc might increase the therapeutic index of carboplatin in the treatment of brain tumors. PMID- 1733557 TI - Modulation of the cellular pharmacokinetics of ara-CTP in human leukemic blasts by dipyridamole. AB - The effect of dipyridamole (DP) on the cellular retention of 1-beta-D arabinofuranosylcytosine (ara-C) and its metabolites was examined in leukemic blasts that had been isolated directly from bone marrow aspirates from patients afflicted with acute myeloid leukemia (AML). When AML cells were loaded for 2 h with 1 microM [3H]-ara-C and then transferred to ara-C-free medium, total intracellular concentrations of radiolabel and [3H]-ara-C 5'-triphosphate [3H] ara-C-CTP rapidly declined. After 8 h, total intracellular levels of tritium were 4.4 times higher if 10 microM was included in the washout medium; however, the majority of this intracellular radiolabel corresponded to [3H]-uridine arabinoside ([3H]-ara-U) and [3H]-ara-C. DP significantly increased the mean t1/2 for [3H]-ara-CTP from 102 to 136 min (P less than 0.01), but this effect was much less pronounced than that obtained for total tritium and the increase was quite variable (0-70%; median, 19%). The presence of DP in the washout medium also increased the incorporation of ara-C into DNA and the formation of ara-CDP choline. The level of ara-CDP-choline continued to increase in both DP-containing and DP-free media for the first 4 h following drug removal and the formation of ara-CDP-choline continued during the first few hours in ara-C-free medium. At the end of the 8-h wash in DP-containing medium, the cellular concentration of ara CDP-choline was equivalent to that found at the beginning of the washout period. Although statistically significant, the effect of DP on ara-CTP retention in AML blasts was much less pronounced than that previously observed in L5178Y leukemia. The former cells exhibited only 10% as many nucleoside transport carriers as did the L5178Y cells as measured by their capacity to bind [3H] nitrobenzylmercaptopurine riboside (NBMPR). The effect of DP in prolonging ara CTP retention was proportional to the number of [3H]-NBMPR binding sites. This suggests that in patients cells that exhibit extremely low transport capacity, most of the net catabolism occurs via deamination, and further inhibition of transport by DP in an effort to improve cellular retention of ara-C has little effect on ara-CTP catabolism. PMID- 1733558 TI - Assembly of prednimustine low-density-lipoprotein complexes and their cytotoxic activity in tissue culture. AB - The lipophilic anticancer drug prednimustine was incorporated into model low density-lipoprotein (m-LDL) using a novel modified method. The major steps of this procedure involve the preparation of a microemulsion containing the drug and the complexing of this emulsion with apolipoprotein B (apo B) that has been delipidated by heptane extraction. The resulting particles contained on average 338 mol prednimustine/mol apoB and exhibited a diameter that was ca. 2.5 times that of native LDL. The cellular binding, uptake, and metabolism of the complexes were found to be similar to those of native LDL. The cytotoxic activity of the complexes was monitored in vitro against T-47D breast cancer cells and normal 3T3 fibroblasts. The activity of prednimustine in m-LDL against T-47D cells after 24 h treatment was nearly 50% higher than that of the free drug, whereas in 3T3 cells the difference was relatively small. The results indicate that it is possible to target drug/m-LDL complexes to cancer cells exhibiting high LDL receptor activity. PMID- 1733559 TI - Suitability of cisplatin solutions for 14-day continuous infusion by ambulatory pump. AB - The stability of cisplatin (DDP) solutions (1 and 1.6 mg/ml in saline-mannitol) in plastic infusion bags was studied for up to 14 days at 25 degrees C, 37 degrees C and 60 degrees C. Small changes in the solution were observed, but no evidence of any decomposition product was seen. Some precipitation of DDP was seen in the 1.6-mg/ml solution at the lower temperatures. Fluid loss from the bags was significant at the higher temperatures. PMID- 1733560 TI - Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells. AB - Purified human alpha-thrombin stimulates phosphoinositide turnover as a necessary step in its stimulation of fibroblast cell proliferation. Since phosphoinositide turnover releases diacylglycerol, which activates protein kinase C, we postulated that long-term exposure to thrombin might promote cellular transformation in a manner similar to long-term exposure to phorbol esters, which also activate protein kinase C. The present studies show that chronic exposure of BALB/c 3T3 cells (subclone A31-1-13) to thrombin (5 micrograms/ml) led to a 4- to 20-fold increase in the frequency of morphological transformation over controls as determined by induced foci in monolayer cultures. The foci appeared to represent true transformants as cells from randomly selected foci grew in soft agar and had saturation densities 2- to 3-fold higher than control cells. Acute thrombin treatment for 24 h resulted in small but statistically significant (P less than 0.05) increases in morphological transformation with or without promotion by phorbol myristate acetate, indicating that thrombin can act as a weak initiator or complete carcinogen in this test system. Initiation of cells with low levels of 3-methylcholanthrene followed by promotion with thrombin caused a greater enhancement of morphological transformation (P less than 0.005). Thus, it appears that most of the stimulation of in vitro cell transformation by thrombin may be due to its promotional activity. These results raise the possibility that thrombin released locally following tissue injury or chronic irritation may play a role in cellular transformation and tumor development, especially in tissues sensitized by exposure to initiating carcinogens. PMID- 1733562 TI - Reaction product inactivation of aryl sulfotransferase IV following electrophilic substitution by the sulfuric acid ester of N-hydroxy-2-acetylaminofluorene. AB - Rat liver N-hydroxy-2-acetylaminofluorene (N-OH-2AAF) sulfotransferase activity is mediated by aryl sulfotransferase IV (AST IV) and causes the bioactivation of N-OH-2AAF to a highly reactive sulfuric acid ester form putatively capable of inducing liver cancer. Dietary administration of 2-acetylaminofluorene (2AAF) to induce hepatocarcinogenesis in rats has been shown to cause a rapid loss in N-OH 2AAF sulfotransferase activity. A possible mechanism for the in vivo loss in sulfotransferase activity may be the PAPS-dependent, sulfotransferase-catalyzed, reaction product inactivation of the enzyme by covalent reaction with the N-OH 2AAF sulfuric acid ester. In vitro studies to evaluate this possibility utilized a highly purified form of AST IV and measured the extent of PAPS-dependent interaction between the enzyme and N-OH-2[9-14C]AAF. The results showed the presence of a adenosine-3'-phospho-5'-phosphosulfate (PAPS)-dependent 14C labeling of AST IV. The labeling could be blocked if the sulfotransferase inhibitor pentachlorophenol was present. Analysis of 14C-labeled AST IV following alkaline digestion and chromatography of digestion products indicated that AST IV cysteine and methionine residues were primary sites of 2[9-14C]AAF adduction. Studies involving the pretreatment of AST IV with PAPS and N-OH-2AAF prior to the measurement of N-OH-2AAF sulfotransferase activity showed a close parallel between formation of the AST IV cysteine-2AAF adduct and loss of activity. Similar studies showed that enzyme inactivation and cysteine-2AAF adduct formation could be blocked when excessive amounts of a competing nucleophile, methionine, were present during the pretreatment step, suggesting that inactivation does not proceed by a mechanism-based process. Finally, experiments involving prior reaction of AST IV with the thiol-blocking agent, N ethylmaleimide, before measurement of enzyme activity showed essentially full loss of sulfotransferase activity and suggested that formation of AST IV cysteine 2AAF adducts could be a mechanism for enzyme inactivation. These results indicate that the in vitro inactivation of AST IV by the reactive N-OH-2AAF sulfuric acid ester is accompanied by covalent binding to AST IV, possibly through the formation of cysteine-2AAF adducts, and suggests that this mechanism merits further consideration as a basis for the loss of N-OH-2AAF sulfotransferase activity in vivo. PMID- 1733561 TI - Molecular dosimetry of urinary aflatoxin-N7-guanine and serum aflatoxin-albumin adducts predicts chemoprotection by 1,2-dithiole-3-thione in rats. AB - Hepatocellular carcinoma has one of the poorest 5 year survival rates of any human cancer. Preventive measures offer the best possibility of ameliorating this disease and chemoprotective agents are being developed for this purpose. The dithiolethiones, including oltipraz and the unsubstituted molecule 1,2-dithiole-3 thione, have been shown to be potent inhibitors of aflatoxin-induced hepatic tumorigenesis in rats. However, subsequent evaluation of dithiolethiones or other chemoprotective agents in human clinical trials will require the development of intermediate, non-invasive biomarkers to evaluate the efficacy of these interventions. In this study, levels of molecular dosimetry biomarkers for determining genotoxic damage caused by aflatoxin B1 have been measured in a chronic exposure model with male F344 rats wherein half the animals were fed a diet supplemented with 0.03% 1,2-dithiole-3-thione to lower their risk for tumors and the other half were fed unsupplemented AIN-76A diet and were at high risk for tumor development. Levels of hepatic aflatoxin-DNA adducts, serum aflatoxin albumin adducts and excreted aflatoxin-N7-guanine adducts in urine were determined following multiple administrations of 250 micrograms aflatoxin B1/kg body wt on days 0-4 and 7-11 to assess the use of the serum and urinary biomarkers as indices of chemoprotective efficacy. In the rats fed 1,2-dithiole-3 thione, the overall diminutions in the levels of hepatic DNA adducts, urinary aflatoxin-N7-guanine and serum aflatoxin-albumin adducts over the 2 week exposure period were 76, 62 and 66% respectively. This parallelism in reductions of levels of biomarkers relative to target organ DNA adduct burden suggests that these biomarkers are predictive short-term, non-invasive measures for assessing the efficacy of chemoprotective interventions in experimental studies and can be applied to human clinical trials directed at populations at high risk for aflatoxin exposure and primary hepatocellular carcinoma. PMID- 1733563 TI - Protection by chlorophyllin against the covalent binding of 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) to rat liver DNA. AB - Chlorophyllin (CHL), a sodium/copper salt of chlorophyll used in the treatment of geriatric patients, exhibits potent antimutagenic activity in a range of assays in vitro and in vivo. The protective effects of CHL were studied in Sprague Dawley rats using inhibition of carcinogen-DNA binding as an end-point. Animals were administered CHL (150 mg/kg body wt) and [2-14C]2-amino-3-methylimidazo[4,5 f]quinoline (IQ, 50 mg/kg body wt) by single oral gavage. Covalent IQ-DNA binding in liver was determined 8, 24 and 48 h after dosing; CHL inhibited binding at these times by 58, 56 and 46% respectively, compared with rats given IQ alone. The total liver burden of IQ-derived radioactivity was reduced in CHL-treated rats, as was the total amount of radiolabel eliminated in the urine and bile. However, elimination via the feces was increased in rats given CHL, both in terms of total radiolabel eliminated and amount of unmetabolized IQ in dichloromethane extracts of feces. Finally, pretreatment with CHL in the drinking water, or injection of CHL into isolated loops of intestine in situ, reduced the absorption of IQ from the gut. Collectively, these findings indicate that, when administered simultaneously with the carcinogen, CHL attenuates IQ-DNA binding in rat liver by interacting with IQ in the gut and reducing carcinogen uptake, distribution and metabolism. The results suggest that further studies should be conducted with respect to the protective mechanisms and possible anti-carcinogenic properties of CHL. PMID- 1733564 TI - Molecular dosimetry of DNA adducts in C3H mice treated with glycidaldehyde. AB - The formation of DNA adducts in the skin of male C3H mice treated cutaneously with glycidaldehyde (2 or 10 mg/animal) in acetone has been investigated by HPLC coupled with fluorescence detection and 32P-postlabelling analysis. Following a 24 h exposure period, epidermal DNA was isolated from treated dorsal skin and enzymically digested to nucleoside-3'-monophosphates. HPLC-32P-postlabelling analysis of the DNA hydrolysate indicated that a single major cyclic adduct was formed from the reaction of glycidaldehyde with deoxyadenosine residues in mouse skin DNA. This adduct was identified as 3-beta-D-deoxyribofuranosyl-7 (hydroxymethyl)-3H- imidazo[2,1-i]purine-3'-monophosphate by comparison with a synthetic standard. This adduct was stable, strongly fluorescent and readily detected by HPLC with fluorescence detection. There was no evidence for the formation of deoxyguanosine adducts in epidermal DNA of treated animals. Glycidaldehyde also reacted with calf thymus DNA in vitro at pH 7.0 to give the same deoxyadenosine adduct observed in vivo. At pH 10, however, this was a relatively minor product and the major adduct was 5,9-dihydro-7-(hydroxymethyl)-9 oxo-3-beta-D-deoxyribofuranosyl-3H-imidazo[1,2-a]purine-3'- monophosphate formed by the initial reaction of glycidaldehyde with deoxyguanosine residues. PMID- 1733565 TI - Effects of phenobarbital on I-compounds in liver DNA as a function of age in male rats fed two different diets. AB - The age-dependent effects of diet and of phenobarbital (PB), a known promoter of hepatocarcinogenesis, on indigenous DNA adducts (I-compounds) were studied by the 32P-post-labeling technique. Late-gestation female Sprague-Dawley rats were fed either AIN-76A semisynthetic or Teklad cereal-based diet. At 21 days after birth, the male pups were weaned and continued on the diets, with half of each dietary group receiving 0.05% PB mixed into the diet for 2, 4 and 8 months. Age-dependent increases in I-compound levels were observed. In addition, both the levels of individual I-compounds and the overall number of I-compounds were greater in rats fed the Teklad cereal-based diet than in those fed the AIN-76A diet. Independent of the parent diet, PB administration reduced the levels of the majority of I compounds in a time-dependent manner. This effect of PB was detected earlier in the Teklad-fed than in the AIN-76A-fed group. In contrast to the I-compounds, a second group of spots, termed reverse I-compounds, declined between 2 and 4 months and, especially in AIN-76A-fed animals, tended to increase when PB was administered. It is hypothesized that alterations of DNA modification patterns may play a role in diet-modified hepatocarcinogenesis promoted by PB. PMID- 1733566 TI - Status of ornithine decarboxylase activity and DNA synthesis in mancozeb-exposed mouse skin. AB - The effect of mancozeb, a fungicide, on mouse skin ornithine decarboxylase (ODC) activity and DNA synthesis was studied. ODC activity was induced after topical application of mancozeb and exhibited a peak level at 5 h. This ODC induction was dependent on the dose of mancozeb applied. Cycloheximide, an inhibitor of protein synthesis, inhibited the mancozeb-caused ODC induction, indicating the effect on enzyme protein synthesis. The rate of DNA synthesis was also increased by mancozeb, as indicated by increased [3H]thymidine incorporation into skin DNA. Induction of ODC activity and DNA synthesis are among the events probably involved in the tumorigenic action of mancozeb on mouse skin. PMID- 1733567 TI - Mutations recovered in the Chinese hamster aprt gene after exposure to carboplatin: a comparison with cisplatin. AB - Platinum-based compounds such as cisplatin and carboplatin are currently used for the treatment of a variety of solid tumors. Their primary mode of action involves the production of cross-links in DNA. These compounds induce mutations in bacterial as well as in mammalian cells. Previously we determined the sequence specificity and mutational outcome in the Chinese hamster aprt gene in mutants isolated after exposure to cisplatin. The second-generation platinum drug, carboplatin, is of clinical relevance because it displays different and less toxic effects. Here we report the mutagenic specificity of this related compound. Mutations recovered after exposure to carboplatin display the same preference for sequences that contain 5'-AGG-3', 5'-AGA-3' and 5'-GAG-3' as was found for cisplatin. We thus conclude that the mutagenic outcome of exposure to carboplatin and cisplatin respectively, is similar, if not identical. PMID- 1733568 TI - Transplacental and transgeneration carcinogenic effect of 7,12 dimethylbenz[a]anthracene: relationship with ras oncogene activation. AB - Transgeneration transmission of the carcinogenic action of 7,12 dimethylbenz[a]anthracene (DMBA) was studied in two generations of mice using transplacental DMBA initiation followed by postnatal skin tumor promotion with 12 O-tetradecanoylphorbol-13-acetate (TPA) in the first generation (F0) and only promotion in the second generation (F1). Local application of TPA resulted in increased skin tumor yield in both the in utero DMBA-exposed mice and their progeny (P = 0.0002 and P = 0.0941 respectively compared to control). Similarly, lung tumor incidence was increased in the two generations of mice (P less than 0.0001 and P = 0.0080 respectively). The results suggest transgeneration transfer of the effect of DMBA. A to T mutation at the second base of codon 61 of the Ha ras oncogene was found in skin tumors of DMBA-exposed mice, but not in tumors induced by TPA without initiation. Analysis of Ki-ras codon 61 in seven lung tumors from DMBA-treated mice revealed three types of mutation: two cases with CA[C or G or T], one case with CCA and one case with CTA (the remaining cases having only the wild type). Six of these mice also had skin tumors, which contained A to T mutation at the second base of codon 61 of the Ha-ras gene in five cases. Thus mutations of different ras genes were found in skin and lung tumors from the same animals. In the progeny (F1) of DMBA-exposed F0 mice, only skin tumor samples were available for oncogene analysis and none contained the Ha ras mutation. The results confirm our previous finding that initiation of skin and lung tumorigenesis can be transmitted transgenerationally. On the other hand, our data from a limited number of skin tumors suggests that ras gene mutation may not be critically involved in this transmission. PMID- 1733569 TI - Development of a quantitative in vitro transformation assay for kidney epithelial cells. AB - A quantitative in vitro transformation assay has been developed for the first time using primary rat kidney epithelial (RKE) cells. RKE cells were grown in a 50:50 mixture of 3T3 conditioned medium and DF8 medium composed of Ham's F 12/DMEM supplemented with ferrous sulfate, vasopressin, transferrin, sodium selenite and 10% fetal bovine serum. Colony forming efficiency of cells plated in this medium was high, ranging from 2.4 to 16%. Normal RKE cells treated with N methyl-N'-nitro-N-nitrosoguanidine (MNNG) became transformed to a preneoplastic state of enhanced in vitro growth potential and formed large colonies of morphologically altered cells, whereas RKE cells treated with vehicle alone ceased proliferating and/or sloughed off the dish within 4-6 weeks. Relative survival and percent transformation frequency (Tf) of RKE cells exposed to MNNG were inversely proportional and both were dose dependent. MNNG concentration of 0.5, 1.0 and 2.0 micrograms/ml resulted in transformation frequencies of 0.13, 0.37 and 1.1% respectively (n = 4). Morphologically transformed colonies gave rise to cell lines with indefinite growth capacity and neoplastic potential. One of six transformed RKE cell (TRKE) lines injected into nude mice produced adenocarcinomas. This assay represents the first in vitro model for studying mechanisms of chemical transformation of normal kidney epithelial cells and may also be useful as a screen for identifying potential renal carcinogens. PMID- 1733570 TI - Relationship between the depletion of O6-methylguanine-DNA methyltransferase by O6-methylguanine and the stimulation of DNA synthesis and growth of cultured chick hepatocytes. AB - O6-Methylguanine-DNA methyltransferase (O6-MT) has been described as a DNA repair enzyme that reverses alkylation damage at the O6 position of guanine in DNA. We demonstrate that the concentration of this protein decreases immediately prior to DNA synthesis in cultured chick hepatocytes. If intracellular levels are experimentally depleted by treatment of cultures with O6-methylguanine, DNA synthesis occurs as an associated resultant. This effect is dose dependent and can be followed by discernible morphological changes of organoids in culture. Increased and altered growth caused by O6-methylguanine was quantified and was also found to be dose dependent. Therefore, O6-MT may play a role in the regulation of DNA synthesis. PMID- 1733571 TI - Diet-induced increase of colonic bile acids stimulates lytic activity of fecal water and proliferation of colonic cells. AB - The proposed intermediate steps in the relationship between a diet-dependent increase in colonic bile acids and proliferation of colonic cells were studied in rats. Male Wistar rats were fed diets supplemented with increasing amounts of steroids to increase the bile acid concentration of the colon. After 2 weeks, in vivo colonic proliferation was measured using tritiated thymidine incorporation into DNA. Luminal lytic activity was measured as lysis of erythrocytes by fecal water. To quantify hemolysis in the presence of fecal water, a method was developed which measures Fe-release using atomic absorption spectrophotometry. This method proved to be superior to the cell-counter method published earlier. Our results showed that steroid supplementation increased, in a dose-dependent manner, the total fecal and the soluble bile acid concentration as well as lytic activity of fecal water and colonic proliferation. A highly significant correlation between lytic activity of fecal water and colonic proliferation (r = 0.85, n = 24, P less than 0.001) was observed. These results indicate that the increase in colonic proliferation is mediated by diet-dependent increases in soluble colonic bile acid concentration and luminal lytic activity. This sequence of effects illustrates how diet could influence the risk for colon cancer. PMID- 1733572 TI - K-ras oncogene mutations in rat colon tumors induced by N-methyl-N-nitrosourea. AB - We have been studying a rat model of colon cancer in which tumors are induced by direct application of N-methyl-N-nitrosourea (MNU) to discrete areas of the colonic mucosa for a limited period of time. Activation of the ras genes by point mutation has been observed in many experimental tumors, including tumors induced by MNU. To detect potential activating point mutations in the H-ras and K-ras oncogenes in MNU-induced rat colon tumors, DNA samples from 40 adenomas, nine carcinomas, and 14 histologically normal tissue samples from 14 rats--as well as from 16 foci induced on NIH3T3 cells by tumor DNAs--were amplified by the polymerase chain reaction and hybridized with allele-specific oligonucleotide probes. No H-ras point mutations were observed in any of these samples. We did detect K-ras point mutations, however, in four primary tumours--one adenoma (2.5%) and three carcinomas (33%); these mutations were all G----A transitions at the second nucleotide of codons 12 and 13. The absence of detectable ras mutations from the majority of tumors suggests that, in contrast to other animal models utilizing MNU, tumorigenesis in MNU-induced rat colon tumors may predominantly involve activation of genes other than ras. PMID- 1733573 TI - Induction of ornithine decarboxylase in specific subpopulations of murine epidermal cells following multiple exposures to 12-O-tetradecanoylphorbol-13 acetate, mezerein and ethyl phenylpropriolate. AB - Single applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein or ethyl phenylpropriolate (EPP) to mouse skin at appropriate doses cause similar degrees of hyperplasia and comparable levels of induction of epidermal ornithine decarboxylase (ODC) activity. Multiple (n = 5) treatments with these agents, in contrast, resulted in large differences in induced ODC activity (TPA much greater than mezerein greater than EPP) with no differences in the degree of hyperplasia or [3H]thymidine pulse-labeling among the multiple treatment groups. To attempt to explain the cellular basis for the greater ODC-inducing ability of TPA relative to mezerein and EPP in chronic exposure protocols, immunocytochemical and flow cytometric analyses were performed. Immunocytochemistry using an ODC specific polyclonal antibody revealed substantially different pattern of ODC positive cells in chronically exposed epidermis than observed with single exposures. TPA treatment resulted in very pronounced immunostaining of the perifollicular cells, with little evidence of specific staining in the interfollicular epidermis mezerein treatment yielded staining in both interfollicular and some perifollicular areas, while EPP treatment produced the least amount of specifically stained cells, all of which were in the interfollicular epidermis. Flow cytometric analysis of keratinocytes isolated from chronically treated skin identified three distinct subpopulations that bound varying amounts of ODC antibody. Chronic treatment of CD-1 murine epidermis with TPA appeared to cause the expansion of an intermediate sized cell subpopulation that was not apparent with EPP or mezerein. Our results suggest that chronic treatment of murine epidermis with the potent complete tumor promoter TPA leads to the selective expansion of a keratinocyte subpopulation that is hyperinducible for ODC and may be identical to the cells in the perifollicular region previously identified. These observations also suggest that the weaker tumor promoters mezerein and EPP are less capable of causing expansion of this specific subpopulation, which may be an important target cell population for neoplastic transformation in mouse epidermis. PMID- 1733574 TI - Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of female workers exposed to benzene and toluene. AB - Peripheral lymphocyte DNA damage as measured by the method of alkaline filter elution and the frequency of sister chromatid exchange (SCE) in lymphocytes was investigated for a group of 20 female workers of a shoemaking plant who were exposed to benzene and toluene, primarily below the German threshold limit value of 5 and 100 p.p.m. respectively; the results were compared with those from a control group. In the female workers significantly raised (P less than 0.05) SCE values were found. The relative DNA elution rate through polycarbonate filters was significantly increased (P less than 0.001). The elution rate through polyvinylidene fluoride (HVLP) filters showed a tendency to increase (P = 0.052), which must be interpreted as indicating increased DNA strand breakage. The SCE rates of the female workers were significantly correlated (P less than 0.01) with the relative DNA elution rate through HVLP filters. There was no correlation with the actual benzene and toluene uptake measured by personal air monitoring. Four months after cessation of work, DNA strand breakage decreased significantly (P less than 0.05) in blood samples of six reinvestigated female workers. PMID- 1733575 TI - The role of macrophage-derived TNFa in the induction of sublethal tumor cell DNA damage. AB - In previous studies we showed that tumor-associated macrophages isolated from murine mammary tumors are mutagenic to bacteria and mammalian cells and thus may contribute to tumor progression. We reported previously, and confirm here, that inflammatory macrophages induce DNA strand breaks in cultured mammary tumor cells co-incubated at a 1:1 ratio for 1 h. This activity is prevented by inhibitors of arachidonate metabolism or the removal of H2O2 with catalase. In the present study, we show that two antibodies to recombinant murine tumor necrosis factor alpha (rMuTNFa)--a hamster monoclonal antibody (TN3-19.12) and a rabbit polyclonal antibody (Genzyme)--partially protect tumor cells from DNA strand breaks induced by elicited but not resident peritoneal macrophages. Antibody protection was reversed upon the addition of excess exogenous rMuTNFa. Purified rMuTNFa alone was unable to induce DNA strand breaks in the absence of macrophages, indicating that TNFa is necessary but not sufficient to mediate damage. Tumor target cells were completely resistant to the cytotoxic effects of rMuTNFa in the absence of actinomycin D and relatively resistant (in comparison to WEHI 164 clone 13 cells) in its presence. The incomplete protection seen with either catalase or anti-TNF suggests that macrophage-released TNFa, in the presence of other factors, induces non-cytotoxic DNA effects in tumor cells. PMID- 1733576 TI - Stimulation of TGF-beta 1 mRNA concentration in mouse skin treated with benzo[a]pyrene. AB - Topical application of benzo[a]pyrene (B[a]P) at dose rates of 32 or 64 micrograms/week to the dorsal skin of female Swiss (ICR) mice resulted in a marked and rapid increase in concentration of RNA for transforming growth factor beta 1 (TGF-beta 1) in epidermis. Two RNA species 1.9 and 2.5 kb, detected by a mouse TGF-beta 1 cDNA probe, were coordinately expressed. The concentration of these species appeared to be maximal 6-12 h after application, and returned to control levels after 48 h. A second, less intense maximum was observed 72-96 h after treatment. Similar effects were observed in CD-1 and HRS (both hr/hr and hr/+) mice, which are also sensitive to B[a[] tumorigenesis. In comparison with 32 and 64 micrograms/week a dose rate of 16 micrograms/week was essentially without activity in increasing TGF-beta 1 RNA concentration. All three dose rates induced an increase in epidermal RNA for ornithine decarboxylase, however, and with kinetics similar to those observed with the potent tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The results obtained support other findings made in this laboratory, that at high dose rates above 16 micrograms tumorigenesis by B[a]P involves a strong tumor-promoting component. The latter further appears to be mediated by increased TGF-beta 1 expression. PMID- 1733577 TI - Prevalence of tumor prevention rather than tumor enhancement when repetitive UV radiation treatments precede initiation and promotion. AB - UV irradiation can act as a tumor initiator in mouse skin, yet repetitive UV irradiation can systemically prevent chemically induced two-stage skin tumorigenesis. The present study addressed the question of whether repetitive dorsal UV irradiation would enhance or inhibit subsequent initiation and promotion applied dorsally. Approximately 4.25 x 10(5) J/m2 was applied intermittently to 30 shaved CDF1 mice over an 8 week period. Mice were then initiated dorsally with 100 micrograms of 7,12-dimethylbenz[a]anthracene and subsequently promoted with 7.5 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) applied twice weekly for 19 weeks. Initiated and promoted mice that had been treated repetitively with 1.06 x 10(4) J/m2 showed a decrease in tumor incidence from 92 to 28%, and a reduction in tumor yield per mouse from 5.35 to 0.58, at 19 weeks after the first TPA treatment. Histological analysis revealed that the UVB radiation treatments used in these experiments did not produce permanent loss of epidermal cells or sebaceous gland atrophy. When the same dose of UVB irradiation was applied after initiation and promotion, no increased conversion of papillomas to carcinomas was found, within a 48 weeks experimental duration. Thus, repetitive UV irradiation prevented rather than enhanced subsequent two-stage tumorigenesis. Repetitive UVB irradiation at late stages of promotion failed to enhance conversion of papillomas to carcinomas within the time frame in which chemical initiators mediate conversion to malignancy. PMID- 1733578 TI - High-performance liquid-chromatographic measurement of plasma creatinine in newborns. AB - This HPLC method for measuring plasma creatinine is based on cation-exchange chromatography and is particularly suitable for use with specimens from babies. A short chromatographic run is performed after simple protein precipitation with zinc sulfate and addition of an internal standard, N-methylnicotinamide. The standard curve for the method is linear up to 200 mumol/L, and analytical recovery of added creatinine is between 101% and 103%. Between-batch precision (CV) is less than 3% for mean creatinine values of 103 and 164 mumol/L. The method is free of interference from other metabolic components and drugs commonly used in neonates in routine clinical practice. Using specimens from neonates, I compared this method with a routinely used automated alkaline picrate method (from Randox Labs., performed on a Cobas MIRA analyzer). Linear-regression analysis yielded a correlation coefficient of 0.90, a slope of 1.00, and an intercept of +0.8 mumol/L. This HPLC method for creatinine should be of use in those circumstances where the alkaline picrate method is known to produce dubious results; however, the latter method is probably more suitable for routine use. PMID- 1733579 TI - Severe unexplained hypophosphatemia. PMID- 1733580 TI - Monitoring cyclosporine in liver-transplant recipients: effects of clinical status on the performance of two monoclonal antibody-based methods. AB - The characteristics of the Abbott selective fluorescence polarization immunoassay for cyclosporine in whole blood (TDXSP) were compared with the Incstar radioimmunoassay by using kit standards (INCSP) or TDXSP standards (INCTDX) with samples from adult (48) and pediatric (24) liver-transplant recipients and a further 32 control specimens. The TDXSP assay was faster, less labor intensive, and more precise at higher concentrations; it gave results a median of 5 micrograms/L lower than INCSP values, irrespective of biliary T-tube status, patient's age, or severity of cholestasis in nine patients, comparisons being made for serum bilirubin more than eight times normal or less than 50 mumol/L. However, both assays overestimated INCTDX values by approximately 10%. There was a progressive increase in the ratio of TDXSP to both INCSP and INCTDX results in 57 samples stratified in relation to serum bilirubin concentrations. Cross reactivity of TDXSP with cyclosporine metabolites M1 (23%) or M17 (12%) was greater than for INCSP (15% and 5%, respectively) or INCTDX (22% and 4%, respectively), but the converse was true with M21 (2% for TDXSP vs 4% and 8%, respectively). Some overestimation of cyclosporine whole-blood concentrations (relative to INCTDX results) may be detected with either the TDXSP (because of cross-reactivity with metabolites) or the INCSP assays (probably because of matrix effects). The similar magnitude of these overestimations suggests that alternative factors such as speed, precision, and cost may influence which method one selects for use in routine monitoring. PMID- 1733581 TI - One-step, labeled-antibody assay for measuring free thyroxin. I. Assay development and validation. AB - We describe a one-step, labeled-antibody radioassay for measuring free thyroxin (FT4) in serum or plasma, based on a novel principle. FT4 in the sample competes with a gross molar excess (over antibody) of a cross-reactant (L triiodothyronine, T3), chemically coupled to magnetizable polymer particles, for binding to avid 125l-labeled monoclonal anti-thyroxin antibodies. As in conventional immunoassays, 125I counts bound to the solid phase (T3-magnetizable particles) are inversely proportional to sample FT4 concentration. We demonstrate here the development and technical validity of this new method. PMID- 1733582 TI - Ektachem slides for direct potentiometric determination of sodium in plasma: effect of natremia, blood pH, and type of electrolyte reference fluid on concordance with flame photometry and other potentiometric methods. AB - With electrolyte reference fluid (ERF)00, results from Kodak Ektachem slides for the direct potentiometric assay of sodium in plasma were significantly correlated with results from flame photometry, but also appeared to be systematically higher, especially in hypernatremic patients. Indirect potentiometry with the Technicon RA-1000 yielded intermediate values. In 23 hypernatremic patients with greater than or equal to 6 mmol/L difference in sodium between Ektachem ERF00 and flame photometry, a clinical survey disclosed the frequent association of large between-method differences with renal failure, diabetes mellitus, and gastrointestinal disease. However, there was no correlation between differences in sodium on the one hand and anion gaps or (lipo)protein concentrations on the other, nor did in vitro addition studies implicate metabolites that often accumulate in the above-mentioned disorders. Unlike indirect methods, sodium measurements by direct potentiometry on Ektachem and Corning were influenced by in vitro changes of pH between 7.0 and 7.9. However, in a group of patients that included many acidotic individuals, between-method differences in sodium appeared not significantly correlated with in vivo blood pH. Use of the equitransferant ERF04 on Ektachem strongly diminishes the systematic differences with flame photometry, reduces the pH-dependency of the results to that of the direct Corning method, and brings the mean analytical recovery of sodium to below 95% (instead of 115% previously) without affecting the ability of Ektachem slides to avoid spuriously low results in the presence of increased (monoclonal) protein concentrations. PMID- 1733583 TI - Elimination of matrix effects in electrothermal atomic absorption spectrophotometric determinations of bismuth in serum and urine. AB - A sensitive and precise electrothermal atomic absorption spectrophotometric method for determining bismuth concentration is described. Protein precipitation and the use of a palladium modifier reduce the problems of foaming and permit the use of a higher ashing temperature. The detection limit of the assay is 0.9 nmol/L. Total CVs (intra- and interassay) for serum ranged from 3.5% to 15.1% and for urine from 4.8% to 14.5% at concentrations of 60.0 and 6.0 nmol/L, respectively. Analytical recoveries of bismuth added to serum and urine were 102% and 103% over the same range. The method is robust and reproducible and can be accurately calibrated with aqueous standards. PMID- 1733584 TI - Monoclonal fluorescence polarization immunoassay evaluated for monitoring cyclosporine in whole blood after kidney, heart, and liver transplantation. AB - In a prospective study we evaluated a novel fluorescence polarization immunoassay (FPIA) for determining cyclosporine (CsA) in whole blood. FPIA uses a monoclonal antibody and is performed on the TDx (Abbott). The within-series (CV less than 2%) and between-days (CV less than 3.3%) precision of the assay was excellent. The results obtained by the monoclonal FPIA in samples from transplant patients (n = 100) averaged 31.9% and 20.2% higher than those by HPLC and a specific radioimmunoassay (INCStar), respectively. Results by all three methods correlated well. Follow-up studies during the early course after liver transplantation, however, suggested that high metabolite concentrations affect FPIA results. This is explained by previously described cross-reactions of the monoclonal antibody with some CsA metabolites. The FPIA results in samples of such patients should be interpreted cautiously. PMID- 1733585 TI - Methods for measuring plasma hemoglobin in micromolar concentration compared. AB - Of eight methods examined for measuring plasma hemoglobin in micromolar concentration, all exhibited acceptable linearity, reproducibility, and concurrence except when specimens were icteric or lipemic or contained methemoglobin or methemalbumin. Measurement of absorbance at 578 nm with an Allen correction permits precise assay of plasma oxyhemoglobin concentration as low as 0.01 g/L (1 mg/dL, 0.16 mumol/L), unaffected by hyperlipidemia or hyperbilirubinemia. Discrepancies between methods occurred in 11.6% of a consecutive series of 50 nonicteric patients' plasma specimens. Examination of absorption spectra is helpful when discrepancies are observed between methods. The presence of methemalbumin or methemoglobin in plasma is not recognized by methods that measure only oxyhemoglobin. Increased ceruloplasmin or beta-carotene does not significantly affect results. PMID- 1733586 TI - Association between magnesium, calcium, phosphorus, copper, and zinc in umbilical cord plasma and erythrocytes, and the gestational age and growth variables of full-term newborns. AB - We determined reference values in umbilical cord plasma and erythrocytes for magnesium, total calcium, phosphorus, copper, and zinc, and then calculated correlations and stepwise-regression equations in 66 white full-term newborn infants (35 boys, 31 girls). Only infants meeting certain optimal criteria and benefiting from excellent maternal conditions and uncomplicated pregnancies were included. There were no significant sex-related differences at birth among the variables studied. Gestational age was positively correlated with erythrocyte zinc (P less than 0.001), and plasma calcium was positively correlated with erythrocyte copper (P less than 0.001). Plasma copper proved to be the most significant variable in the stepwise-regression equation for birth height as the dependent variable. The most significant regressors accounting for birth weight were erythrocyte zinc followed by plasma zinc. PMID- 1733587 TI - Simple quantitative measurement of serum choriogonadotropin compared with immunoradiometric, immunoenzymometric, and chemiluminescent assays. AB - We evaluated a new simplified quantitative method (Tandem Icon QSR; Hybritech) for choriogonadotropin (hCG), which could theoretically be performed in a ward or with outpatients. The method was compared with immunoradiometric (Bioclone Australia), chemiluminescent (Amerlite; Amersham), and immunoenzymometric assays (Stratus; Dade). We analyzed by each of the methods 104 serum samples from pregnant and nonpregnant patients. For quantitative hCG values indicative of pregnancy (greater than 25 int. units/L), excellent correlation was observed between the Tandem Icon method and the other standard laboratory assays (r = 0.995, 0.990, and 0.992, respectively). Occasional problems arose because of the instability of Tandem Icon QSR reagents at room temperature but this was resolved by storing the reagents at 4 degrees C. We conclude that this simplified quantitative method for hCG is reliable and suitable for use outside of the routine immunoassay laboratory. PMID- 1733588 TI - Effect of precipitation and centrifugation conditions on high-density lipoprotein cholesterol measured with phosphotungstate-magnesium reagent. PMID- 1733589 TI - Measurement of low-density-lipoprotein cholesterol in serum: a status report. AB - Current recommendations of the Adult Treatment Panel and the Children and Adolescents Treatment Panel of the National Cholesterol Education Program make the concentration of low-density lipoproteins cholesterol (LDL-C) in serum the basis for the classification and treatment of hypercholesterolemia. Numerous methodologies for the determination of serum LDL-C concentrations, in research and clinical laboratories, have been described. Here, we review the principles, performance, and limitations of major current methodologies for determining LDL-C concentrations. These methods include sequential and density-gradient ultracentrifugation, chromatographic and electrophoretic techniques, and precipitation methods. In addition, the advantages and disadvantages of estimating LDL-C concentration by the Friedewald equation, the most commonly used approach in clinical laboratories, are addressed. PMID- 1733590 TI - Heparinized plasma is an unacceptable specimen for ammonia determination. PMID- 1733591 TI - Ouabain as endogenous digitalis-like factor in animals? PMID- 1733593 TI - Inefficiency of diagnostic efficiency. PMID- 1733592 TI - Adenosine deaminase, acquired immunodeficiency syndrome (AIDS), and hepatitis B infection. PMID- 1733594 TI - Reflotron method for high-density lipoprotein evaluated for venous and capillary blood. PMID- 1733595 TI - Improved stability of the Hitachi 717 electrolyte unit. PMID- 1733596 TI - Thermal effects on serum analyte concentrations. PMID- 1733597 TI - Improvement of apolipoprotein E phenotyping by isoelectric focusing/immunofixation. PMID- 1733598 TI - New enzymatic CO2 slide on the Ektachem 700 XR analyzer eliminates interference from nitrate/nitrite ions. PMID- 1733599 TI - Oligoclonal banding in sera of hospitalized patients. PMID- 1733600 TI - Development of an immunoradiometric assay kit for ventricular myosin light chain I with monoclonal antibodies. PMID- 1733601 TI - Interlaboratory survey of methods for measuring human anti-mouse antibodies. HAMA Survey Group. PMID- 1733602 TI - One-step, labeled-antibody assay for measuring free thyroxin. II. Performance in a multicenter trial. AB - The technical and diagnostic performance of a labeled antibody radioassay for free thyroxin (Amerlex-MAB* FT4) was examined in a multicenter trial. The overall mean within-assay precision (CV) in eight centers was 6.2% at 30 pmol/L and 3.6% at 13 pmol/L concentrations of FT4. Between-assay precision was 5.4% at 18 pmol/L and 6.8% at 50 pmol/L. The euthyroid central 95% reference range for FT4 was 11.3 to 24.3 pmol/L. Results of the method correlated well with those of an analog radioimmunoassay: [Amerlex-MAB* FT4] = 1.09 [Amerlex-M FT4] + 1.50 pmol/L (r = 0.96, n = 732). Clinical performance of the assay was better than that of first generation analog tracer assays for sera from patients with nonthyroidal illness or binding-protein abnormalities. PMID- 1733603 TI - Application of neural networks to the interpretation of laboratory data in cancer diagnosis. AB - Neural networks are a relatively new method of multivariate analysis. The purpose of this study was to investigate the ability of neural networks to differentiate benign from malignant breast conditions on the basis of the pattern of nine variables: patient age, total cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, albumin, the tumor marker CA15-3, and the Fossel index (measurement of methylene and methyl line-widths in proton NMR spectra). The laboratory analyses were made with blood plasma or serum specimens. The neural network was "trained" with 57 patients: 23 patients with breast malignancies and 34 patients with benign breast conditions. A neural network with nine input neurons, 15 hidden neurons, and two output neurons correctly classified all 57 patients. The ability of the network to predict the diagnoses of patients that it had no encountered in training was tested with a separate group (cross-validation group) of 20 patients. The network correctly predicted the diagnoses for 80% of these patients. For comparison we analyzed the same sets of 57 training patients and 20 cross-validation patients by quadratic discriminant function analysis. The quadratic discriminant function, calculated from the same 57 patients used to train the neural network, correctly classified 84% of the 57 patients, and correctly diagnosed 75% of the 20 cross-validation patients. The results suggest that neural networks are a potentially useful multivariate method for optimizing the diagnostic utility of laboratory data. PMID- 1733604 TI - Screening for defined cystic fibrosis mutations by solid-phase minisequencing. AB - We have developed a rapid method for the quantitative detection of point mutations and deletions. In this minisequencing method, enzymatically amplified DNA, 5'-biotinylated in one strand, is bound to a solid phase and denatured. A detection primer, constructed to end immediately before the mutation, is annealed to the immobilized single-stranded template and elongated with a single, labeled deoxynucleoside residue. We have applied the solid-phase minisequencing method to the detection of the major mutation, delta F508, causing cystic fibrosis (CF). In the presence of the allele with the delta F508 mutation, [3H]dTTP is incorporated; with the nonmutated allele, [3H]dCTP is incorporated. Thus, samples from heterozygous individuals allow the incorporation of both labels. The method was evaluated by analyzing 59 coded DNA specimens collected from 20 Finnish CF patients and their parents. The ratio of [3H]C to [3H]T gave unambiguously the allele combination. The solid-phase minisequencing method was also applicable to the analysis of three CF mutations simultaneously, i.e., delta F508, G542X, and G551D. We conclude that the microtiter-plate-based minisequencing test is an accurate method for the screening of defined sequence alterations in the CF gene. PMID- 1733605 TI - New enzymatic method with tryptophanase for determining potassium in serum. AB - We established a simple and rapid enzymatic method for measuring potassium ion in serum by using tryptophanase (EC 4.1.99.1) purified from Escherichia coli K12 strain (E. coli K12 IFO 3301). The presence of pyridoxal 5-phosphate promotes this enzymatic reaction, and potassium and (or) ammonium ions further accelerate it, with ammonium and potassium ions providing equivalent acceleration. We eliminated endogenous ammonium ion by using glutamate dehydrogenase (GLDH; EC 1.4.1.4), then produced ammonium ion in the presence of tryptophanase, tryptophan, and pyridoxal 5-phosphate. The concentration of formed ammonium ion, which was proportional to that of potassium ion in sample, was determined by adding GLDH to produce NADP+ in the presence of 2-oxoglutarate and NADPH; we then read the change of absorbance at 340 nm. The standard curve was linear for potassium ion concentrations up to 7.00 mmol/L. The within-assay variation (CV) was 0.89% at 5.51 mmol/L and 1.32% at 3.37 mmol/L. The day-to-day CVs were 0.99% at 6.85 mmol/L and 1.71% at 3.52 mmol/L. Analytical recoveries ranged from 98.7% to 108.9%. The correlation coefficient between values obtained with this enzymatic assay (y) and by flame photometry (x) was 0.995: y = 0.984x + 0.091 mmol/L (Sy.x = 0.105, n = 100). The presence of hemoglobin, bilirubin, or other cations little affects this system. PMID- 1733606 TI - Biological variation data applied to the selection of serum lipid ratios used as risk markers of coronary heart disease. AB - The biological variation of several relative lipid quantities, calculated as the ratios between the concentrations of various serum lipids and apolipoproteins, has been estimated over a one-year period. The medians of the within-subject biological coefficient of variation, separated by sex when significant differences exist, were 15.4% for [apolipoprotein A-I]/[apolipoprotein B], 6.8% for [high-density lipoprotein (HDL)-cholesterol]/[cholesterol], 10.5% and 17.6% (women and men, respectively) for [HDL2-cholesterol]/[HDL-cholesterol], 13.6% for [HDL2-cholesterol]/[HDL3-cholesterol], 10.6% for [low-density lipoprotein (LDL) cholesterol]/[apolipoprotein B], 10.6% and 8.7% (women and men, respectively) for [LDL-cholesterol]/[cholesterol], and 6.3% for [LDL-cholesterol]/[HDL cholesterol]. From these data, we have calculated the critical difference for significant change detection, the index of individuality, and the goal for the between-day imprecision. Concerning within-subject biological variation, the best ratios for the detection of risk of coronary heart disease and the monitoring of intervention are [LDL-cholesterol]/[HDL-cholesterol] and [HDL cholesterol]/[cholesterol]. The index of individuality obtained in this study indicates that the use of population-based reference values is inadequate for interpreting the ratios studied. PMID- 1733607 TI - Ion-trap detection of volatile organic compounds in alveolar breath. AB - We describe a method for the collection and microanalysis of the volatile organic compounds in human breath. A transportable apparatus supplies subjects with purified air and samples their alveolar breath; the volatile organic compounds are captured in an adsorptive trap containing activated carbon and molecular sieve. The sample is thermally desorbed from the trap in an automated microprocessor-controlled device, concentrated by two-stage cryofocusing, and assayed by gas chromatography with ion-trap detection. Compounds are identified by reference to a computer-based library of mass spectra with subtraction of the background components present in the inspired air. We used this device to study 10 normal subjects and determined the relative abundance of the volatile organic compounds in their alveolar breath. The breath-collecting apparatus was convenient to operate and was well tolerated by human volunteers. PMID- 1733608 TI - Age-correlated modifications of copper-zinc superoxide dismutase and glutathione related enzyme activities in human erythrocytes. AB - To obtain a comprehensive profile of the erythrocyte antioxidant defense potential during aging, we investigated copper-zinc superoxide dismutase (CuZn SOD), seleno-dependent glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-RD), and glutathione-S-transferase (GSH-S-T) activities in human erythrocytes from 167 apparently healthy subjects, ages one month to 63 years (102 females, 65 males). We found a negative correlation between age and activities of CuZn-SOD (r = 0.362, P less than 0.001), GSSG-RD (r = 0.549, P less than 0.001), and GSH-S-T (r = 0.575, P less than 0.001). In contrast, we found a positive correlation between age and GSH-Px activity (r = 0.401, P less than 0.001). To evaluate aging changes, we divided the subjects into five groups: Group 1 (newborn-age one year), Group 2 (1-11 years), Group 3 (11-25 years), Group 4 (25-40 years), and Group 5 (40-63 years). Significant age-related modifications in erythrocyte enzyme activities appeared in Group 3 for CuZn-SOD, GSSG-RD, and GSH-Px activity, whereas for GSH-S-T activity age-related modifications appeared in Group 2. We found no sex-related differences in erythrocyte CuZn-SOD, GSSG-RD, GSH-Px, and GSH-S-T activities. PMID- 1733609 TI - Automation and the single-gene disorder: cystic fibrosis as a model. PMID- 1733610 TI - Development of time-resolved immunofluorometric assay of vascular permeability factor. AB - We describe a two-site time-resolved immunofluorometric assay for guinea pig vascular permeability factor (VPF) for quantifying VPF in different biological fluids. Antibody against the carboxy terminus (C-IgG) is immobilized on microtiter wells, and antibody against the amino terminus (N-IgG) is labeled with Eu(3+)-chelate. Line 10 tumor culture medium, known to be rich in VPF, is assayed in a two-step incubation. Bound Eu3+ is then quantified by dissociation into a fluorescent enhancement solution, with measurement of the time-resolved fluorescence. The analytical sensitivity is 0.35 VPF unit, and the intra-assay CV is about 20%. The assay is specific for VPF, because pre-treatment with the appropriate C- or N-peptide, or pre-extraction of VPF, greatly decreases fluorescence. The VPF immunoassay is highly correlated (r2 = 0.94) with the Miles permeability assay, the classical bioassay of VPF. In addition, the immunofluorometric assay is about 30-fold more sensitive than the Miles assay. PMID- 1733611 TI - VALAB: expert system for validation of biochemical data. AB - In large laboratories that use "high-throughput" equipment, it is now possible to use artificial intelligence techniques to aid decision making and validation of data. This paper describes an artificial intelligence project, VALAB, that has been carried out in our laboratory. VALAB, an expert system that permits real time validation of data, is designed to be equivalent to validation by the laboratory director. The decision produced by the expert system is based on several factors, including correlation between repeated laboratory results, physiological association between different variables, the hospital department from which the test was ordered, and the patient's age and sex. In 200 abnormal chemistry profiles randomly selected, VALAB's ability to detect abnormal cases (i.e., sensitivity = 0.75) was exceeded by only one of seven laboratory experts. However, all seven experts outperformed VALAB's measured specificity of 0.63. The VALAB system incorporates greater than 4000 rules. Operational since November 1988, it has validated greater than 50,000 medical patients' reports in real time. PMID- 1733612 TI - Prevalence of anti-thyroid peroxidase antibodies in serum in the elderly: comparison with other tests for anti-thyroid antibodies. AB - Autoimmune thyroid disease, especially chronic thyroiditis, is prevalent in elderly women and is probably the major cause of hypothyroidism in this population. The reported prevalence of chronic thyroiditis is variable, depending on the area of residence and the method(s) used to detect the presence of anti thyroid antibodies. The recent finding that thyroid peroxidase (TPO) is the antigen for the thyroid anti-microsomal antibody (AbM) has resulted in the development of sensitive radioimmunoassays (RIA) to detect the presence of AbTPO. We have determined the prevalence of AbTPO (by RIA) in sera from 342 elderly subjects, 248 women and 94 men (mean age 80 years) residing in Reggio Emilia, Italy, and compared the results with other methods for detecting anti-thyroid antibodies, including anti-thyroglobulin (AbTg) and AbM measured by passive hemagglutination (PH) of tanned erythrocytes, and AbM measured by RIA. The prevalence of positive AbTPO was 2.3% in the men and 10.2% in the women, only slightly higher than the prevalence of AbM. However, in the antibody-positive sera, the mean value for AbTPO was approximately 20-fold greater than the upper limit of the normal range, whereas the mean value for AbM was only threefold greater. The prevalence of positive titers for AbM and AbTg measured by PH was far lower, 1.2% and 3.2%, respectively, and those sera weakly positive for AbM and AbTg by PH were strongly positive for AbTPO by RIA. AbTPO RIA may be more useful than AbM and AbTg hemagglutination and AbM RIA for detecting the presence of autoimmune thyroid disease. PMID- 1733613 TI - Neural networks and diagnosis in the clinical laboratory: state of the art. PMID- 1733614 TI - Denaturing gradient gel electrophoresis for rapid detection of latent carriers of a subtype of acute intermittent porphyria with normal erythrocyte porphobilinogen deaminase activity. AB - Acute intermittent porphyria is an autosomal dominant disorder defined by a partial deficiency of porphobilinogen deaminase (EC 4.3.1.8). Clinical manifestations of the disease are characterized by acute attacks of neurological dysfunction often linked to environmental factors. Early diagnosis of gene carriers is important in the prevention of attacks and is usually achieved by determining the porphobilinogen deaminase activity in erythrocytes. However, in a subtype of acute intermittent porphyria, the enzymatic defect is restricted to nonerythropoietic cells. Different mutations have already been described that account for this phenotype in two unrelated families. We previously detected asymptomatic carriers by using mutation-specific probes after in vitro amplification of the target DNA sequence. In this study, we investigated the DNA of eight unrelated subjects with the same subtype of acute intermittent porphyria by using the polymerase chain reaction, with subsequent analysis of the amplified products by denaturing gradient gel electrophoresis. Five of these patients shared the same single-base change. This technique was quite simple and efficient for detecting asymptomatic carriers. Importantly, it is potentially useful for studying families with the same phenotypic subtype of the disease and possibly different mutations in the same DNA region. PMID- 1733616 TI - Alpha rhythm power and the effect of photic stimulation in migraine with brain mapping. AB - The topographic maps of 50 patients suffering from migraine with or without aura were compared to the brain maps of 20 normal controls and 20 patients with tension-type headaches. Only the migraine group showed a significant decrement of alpha rhythm power, during rest with eyes closed, at the posterior areas of the brain, and a significant increment of alpha power at the same regions during IPS at 20 c/sec. PMID- 1733615 TI - Fecal coproporphyrin isomers in hereditary coproporphyria. AB - To see whether the fecal coproporphyrin III:coproporphyrin I (CIII:CI) ratio (determined by HPLC) would be suitable for screening patients at risk of hereditary coproporphyria (HC), we compared such ratios with the lymphocyte coproporphyrinogen oxidase (EC 1.3.3.3) activities (COOX) in 38 subjects from one large family and two smaller families with HC. The CIII:CI ratio was normal (less than 1.3) in adults with normal COOX (greater than 180 nmol/g of protein per hour) and high (greater than 2) in those with low COOX. Results were difficult to interpret in six of 10 children, who had borderline or low COOX but normal fecal CIII:CI ratios. Five subjects with low COOX and abnormal fecal CIII:CI ratios had normal fecal total porphyrin, indicating that the latter investigation alone is inadequate for family studies. The sample for determining the fecal CIII:CI ratio is easier to obtain and the assay is technically less demanding than COOX. We found the fecal CIII:CI ratio suitable for investigation of adults in a family study, but its usefulness in children needs to be established. PMID- 1733617 TI - The Rolandic mu rhythm: a clinical study of the atypical group. AB - We studied 241 patients whose electroencephalograms (EEGs) showed 7-13 Hz arch shaped wave patterns (mu rhythm) that are known to appear in the Rolandic area. The patients were then classified into two groups depending on the conditions of appearance of the mu rhythm. Group I (typical group) consisted of 171 cases. In this group, the presence of the wave patterns was not affected by the opening of the eyes, and it was blocked by spontaneous movements, or when sensorimotor stimulation was applied. The characteristic symptoms for this group were observed in patients diagnosed as having well-controlled epilepsy, psychiatric disorders, collagen diseases, etc. In Group I, the peak lay between the ages 6 through 15. Group II (atypical group) consisted of 70 cases. In contrast to Group I, the presence of the wave patterns in this group was reinforced by drowsiness, photic stimulation and hyperventilation. The characteristic symptoms for this group were observed in patients diagnosed as having intractable epilepsy or organic brain disorders. In Group II the peak lay between ages 11 through 15. However, in Group II the cases were almost equally distributed among the various age groups. Paroxysmal abnormal EEG patterns were found to be jointly present with more frequency in the Group II sample of epileptic patients than the Group I sample. Therefore, when the mu rhythm associated with conditions indicating Group II type patients is observed, care must be exercised in the observation of further progression of the illness, and in searching for the possibility of organic brain disorders. PMID- 1733618 TI - Auditory evoked potentials in Gilles de la Tourette syndrome. AB - Gilles de la Tourette syndrome (TS) has been increasingly studied neurophysiologically as well as clinically. Obsessive-compulsive disorder (OCD) and attention deficit disorder (ADD) have been recognized to be part of the continuum of TS. We recorded brainstem auditory evoked potentials (BAEPs) and long-latency auditory event-related potentials (ERPs) in 20 patients with TS, 10 of whom had ADD and 6 OCD. TS patients with and without OCD and ADD did not differ in BAEP latencies, and no differences were found from normal controls. AEP latencies did not differ between TS patients and controls. TS patients with ADD had longer N100 and N200 latencies than TS patients without ADD, and TS patients with OCD had shorter N200 and P300 latencies. These findings suggest that TS is neurophysiologically heterogenous, and that TS patients with OCD or ADD may differ from those without. PMID- 1733619 TI - Effects of anesthesia and stimulus intensity on posterior tibial nerve somatosensory evoked potentials. AB - Under anesthesia peak latencies occurring up to 75 milliseconds after stimulus onset upon somatosensory evoked potential testing of the somatosensory evoked potential testing of the posterior tibial nerve were not affected by stimulus intensity (between 5 and 19 ma) or by length of time under isoflurane and nitrous oxide up to over 2 hours. When pre- and postoperative tests on patients who were not under anesthesia were compared with results under anesthesia, no significant latency differences were found in relation to stimulus intensity for peaks N30, P40 and N50. For peaks P60 and N75, however, significantly increased latencies were seen during anesthesia, more pronounced and consistent for N75. Amplitudes, however, were affected by both stimulus intensity and anesthesia duration. A curvilinear relationship was found during early anesthesia. Maximum amplitudes were found at 7 or 11 ma stimulus intensity levels, depending upon which peak was analyzed, with lesser amplitudes occurring at both lower and higher stimulus intensity levels. Stimulus intensity and anesthesia interacted such that maximum amplitude occurred, in general, at 11 ma after short duration anesthesia (6') and at 7 ma after long duration anesthesia (125'). Under long duration anesthesia amplitudes were significantly diminished, mostly at the 11 ma intensity level. At 15 and 19 ma intensity levels peak amplitudes remained relatively constant regardless of anesthesia duration and therefore are the intensities to use to monitor changes during prolonged surgeries. When preoperative during prolonged surgeries. When preoperative and postoperative tests were compared to tests under anesthesia, there was a decrease in amplitude under anesthesia, greater for long than short duration anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733620 TI - Changes in reactivity during the 6/second spike and wave complex. AB - This study on a patient with the WHAM form of the 6/sec spike and wave complex shows significant delays in reaction time and increased variability when stimuli were presented during the complex and within 1 second after it, especially when the pattern was high in amplitude and short in duration, and also during theta bursts without the spike component. The similarities and differences between this pattern and the 3/sec spike and wave complex are discussed. PMID- 1733621 TI - Pain and tooth pulp evoked potentials. AB - The purpose of this study was to verify whether the late components (N 140) of TPEPs were a reliable index of pain intensity. In the group with acute pain, except for higher amplitudes of the second negative wave, the plateau phenomenon has been noted. Analgesic and placebo effects indicated that the method used offers more objective than subjective components, because the real value of amplitudes is about 10% of control values for analgesic and between 60 and 70% for placebo. Shorter latency periods were observed in all parts of evoked potentials in the patients suffering from trigeminal neuralgia, as occurrence of a greater number of waves; while amplitudes on the affected side were significantly higher than on the healthy side. PMID- 1733622 TI - A simultaneous comparison of acupuncture needle and insulated needle sphenoidal electrodes for detection of anterior temporal spikes. AB - Uninsulated acupuncture needles have been used as sphenoidal electrodes, but the issue of insulation has not been adequately addressed. In this report, acupuncture needles and insulated needle sphenoidal electrodes were simultaneously used to compare the rate of spike detection, spike amplitude and distribution of maximal spikes from eight spike foci in seven patients with temporal lobe epilepsy. When compared to the insulated needle electrode, the acupuncture needle electrode was equally effective in spike detection, but spike amplitudes tended to be smaller and maximal spikes were less frequently encountered. Thus, insulation has an influence on the spikes recorded by the acupuncture needle sphenoidal electrode. However, the overall effect appears to be not sufficiently different from the insulated needle electrode for the purpose of detecting anterior temporal spikes in outpatient EEG recordings for the diagnosis of temporal lobe epilepsy. PMID- 1733623 TI - EEG characteristics of healthy adults living at higher elevations. AB - EEG data from 400 healthy adult volunteers in the Xining area (with an altitude of 2260 meters) are summarized to show changes in indices of waves, frequencies and amplitude. Analysis and observations were made for tests of eyes open-close, acoustic stimulation and hyperventilation. Differences in EEGs were compared between males and females of various age groups, and between adults living at the higher elevations in Xining and those living on the plains in the Beijing area (altitude 40 meters). Comparisons showed that EEG characteristics of healthy adults at the higher altitude were: an increase in the incidence of abnormality, a decrease of alpha indices, an increase in the number of slow waves, the appearance of spikes and sharp waves, and a reduction in the level of sensitivity to activation tests. PMID- 1733624 TI - Tuberous sclerosis, agenesis of the corpus callosum and Lennox-Gastaut syndrome: mere chance or a new syndrome? AB - The relationship between tuberous sclerosis (TS) and epilepsy on one hand and between agenesis of the corpus callosum (ACC) and epilepsy on the other has been recognized for a long time. Until now, a syndrome characterized by TS, ACC and Lennox-Gastaut syndrome (LGS) has not been described in the literature. Three cases of children, all young male patients, who suffer from TS, ACC and LGS, were presented. The ACC was total in two cases and partial in the third. None of the subjects previously had West syndrome. Two cases showed a slight degree of mental deficiency, while in the third it was very pronounced. In all subjects tonic and astatic seizures were frequent. Antiepileptic therapy improved the clinical picture in one case, while in the other two it remained unchanged. PMID- 1733625 TI - Molecular heterogeneity of human IgA antibodies during an immune response. AB - Human IgA occurs in multiple molecular forms (polymeric and monomeric) and two subclasses which show differential distribution between the mucosal and circulatory compartments of the immune system. However, the molecular form and subclass of specific IgA antibodies are influenced, especially during an immune response, by the type of antigen and duration of the response as well as by the route of exposure. These considerations question previously held notions that polymeric IgA and an increased representation of the IgA2 subclass among circulating antibodies or antibody-secreting cells signify their mucosal origin. Although the functional properties of different molecular forms and subclasses of IgA antibodies are incompletely understood, it appears that there is physiological benefit in the diversity of the IgA immune system. PMID- 1733626 TI - IL-1-like production in adriamycin-induced nephrotic syndrome in the rat. AB - Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis. PMID- 1733627 TI - Primary structure of a monoclonal kappa chain in myeloma with light chain deposition disease. AB - Previous data suggest that structural abnormalities of immunoglobulin light chains may be responsible for non-amyloid light chain deposition disease (LCDD). We report on the complete primary sequence deduced from complementary (c)DNA analysis of a normal-sized kappa chain in a case of myeloma-associated LCDD. The patient's urine contained a kappa type Bence-Jones protein made of monomers and dimers of an unglycosylated kappa chain. The bone marrow myeloma cells contained intracellular kappa and gamma chains by immunofluorescence. Biosynthesis experiments showed the production of normal-sized gamma chains and of kappa chains with the same apparent molecular mass (Mr) in SDS gels as the urinary kappa chain (26,000-27,000). These kappa chains were secreted as assembled IgG molecules and as a large excess of free monomers and dimers. The complete sequence of two identical cDNA clones derived from a normal-sized kappa messenger RNA indicated that this kappa chain belonged to the rare V kappa IV subgroup. The kappa mRNA had an overall normal structure made up of the V kappa IV sequence rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable region differed from the V kappa IV-J kappa 1 germline sequence by 17 amino acid substitutions. The peculiar sequence of the variable region of this kappa chain of a rare subgroup might relate to its tissue deposition. PMID- 1733628 TI - In vivo activation of complement by IgA in a rat model. AB - In this study we investigated the capacity of rat IgA to activate complement (C) in vivo in a rat model. Rat monomeric (m-), dimeric (d-) and polymeric (p-) IgA MoAbs were injected intravenously and assessed for deposition of C3 and C4 on IgA. By ELISA it was shown that both d- and p-IgA bound C3 whereas no binding of C3 by m-IgA was observed. Polymeric IgA was more efficient in binding of C3 as compared with d-IgA. However, in haemolytic assays no consistent decrease of plasma complement levels was observed except for dimeric IgA which induced a marginal consumption of AP50. When rats were pre-treated with cobra venom factor (CVF) to deplete C3, no C3 deposition was found on m-, d- or p-IgA. Neither m- nor d- or p-IgA was able to bind C4 in vivo. In agreement with the results described above, large sized polymeric IgA was shown to be taken up by Kupffer cells (KC) together with C3. No C3 was detected when rats were depleted of C using CVF. Taken together, the experimental data suggest that d- and p-IgA are able to activate C via the alternative pathway in vivo. PMID- 1733629 TI - HIV-induced deletion of antigen-specific T cell function is MHC restricted. AB - When antigen-specific T cells are pulsed by antigen-presenting cells (APC) in the presence of HIV they are functionally deleted following subsequent exposure to syngeneic APC in the absence of HIV. Recombinant soluble HIV envelope (gp120) is able to induce a similar effect which, unlike that induced by HIV, is reversible. Neither HIV nor gp120 affect the ability to respond to IL-2. Thus it is only antigen-specific responses involving the T cell receptor pathways and CD4/MHC class II interaction that appear to be inhibited by HIV-1 and gp120. Furthermore, the functional impairment caused by HIV-1 is specific to the T cells that respond to the antigen in co-culture with HIV, as there is no apparent effect on 'bystander'-activated T cells specific for another antigen. Antigen-specific T cell lines may be deleted by a signalling mechanism which involves molecules other than gp120/CD4 but still requires MHC class II restriction. PMID- 1733630 TI - Regulation of IL-2 beta receptor expression and beta-chain mRNA by human thymocytes. AB - The high affinity form of the human IL-2 receptor (IL-2R) has two known components, the IL-2R alpha (p55) and the IL-2R beta chain (p75). We have previously shown that recombinant IL-2 (rIL-2) could induce the expression of the alpha-chain (p55) on T cells and thymocytes, and increase this expression following suboptimal activation with concanavalin A (Con A) in combination with IL-2. An increase in the accumulation of IL-2R alpha-specific mRNA induced by rIL 2 in T cells and thymocytes had also been documented. We report here that the expression of IL-2R beta on the cell surface can be demonstrated on human thymocytes by the binding of Mik beta1, a MoAb directed against an epitope of the beta-chain. The IL-2R beta chain is constitutively expressed on freshly isolated thymocytes; this expression can be increased in thymocytes activated with Con A in combination with IL-2 or tetradecanoylphorbol 13-acetate (TPA). Blocking the formation of high affinity receptors with a MoAb directed against the alpha-chain of the receptor results in an increase in the display of IL-2R beta as evidenced by binding of MoAb Mik beta1. The accumulation of IL-2R-beta-specific mRNA is observed in freshly isolated thymocytes and it is increased in thymocytes cultured with rIL-2 alone, with Con A, and further enhanced by the addition of rIL-2 in combination with Con A or with TPA. Cyclosporine (CsA), which inhibits the accumulation of lymphokine-specific mRNA of thymocytes, does not inhibit the induction of the accumulation of IL-2R beta-specific mRNA. This is analogous to its effect on the expression of the alpha-chain (p55), and the accumulation of alpha-chain-specific mRNA. PMID- 1733631 TI - Inhibition of the reactive proliferation of lymphocytes by activated macrophages: the role of nitric oxide. AB - The effects of nitric oxide synthesis by activated macrophages on concanavalin A (Con A) stimulated lymphocyte proliferation and the modulation of these events by extraneous L-arginine concentration were investigated. In 1 mM or 5 mM exogenous L-arginine, inhibition of proliferation of a fixed number of lymphocytes was progressively inhibited in the presence of increasing numbers of macrophages. This inhibition was related to increased nitric oxide synthesis by the macrophages and was suppressed in the presence of NG-monomethyl-L-arginine (NMMA), a specific inhibitor of nitric oxide synthesis. Inhibition of nitric oxide synthesis by 500 microM NMMA was less effective at high concentrations of macrophages, and in 5 mM as compared with 1 mM L-arginine. In the absence of exogenous L-arginine, NMMA inhibited lymphocyte proliferation in the presence of low numbers of macrophages but appeared to promote proliferation at high macrophage concentrations. Membrane separation of lymphocytes and macrophages led to loss of the nitric oxide mediated inhibitory effect on lymphocyte division except at the highest concentrations of macrophages used. Inhibition of lymphocyte proliferation could not be associated with L-arginine depletion of the media by macrophages or by the action of nitrite ions, a product of nitric oxide oxidation. PMID- 1733632 TI - The expression of HLA-DR by monocytes from black and from white donors: different requirements for protein synthesis. AB - Epidemiologic data indicates that blacks may be more susceptible than whites to infection by Mycobacterium tuberculosis. Resistance to the in vivo growth of Mycobacteria in mice correlates with the persistence of MHC class II expression by peritoneal macrophages. The expression of HLA-DR by human monocytes from different groups of individuals also differs. The increase in the expression of HLA-DR by monocytes that occurs upon in vitro culture was prevented by the protein synthesis inhibitor cycloheximide (CHX) in a majority of black donors. In contrast, the increase in HLA-DR expression by monocytes from the majority of white donors was unaffected. PMID- 1733633 TI - HLA-associated susceptibility to HIV-1 infection. AB - We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups. PMID- 1733634 TI - Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection. AB - Antibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis like syndrome and a positive ANCA-test who appeared to be infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross sectional study on individuals in different stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of 11 AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIDS-OI patients and in two AIDS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not react with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of monocytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV- individuals were negative. Also immunoprecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV ANCA. PMID- 1733635 TI - Frequencies of HIV-reactive B cells in seropositive and seronegative individuals. AB - Peripheral blood mononuclear cells (PBMC) from HIV-infected seropositive (HIV+) but not from normal, seronegative (HIV-) individuals are known to produce anti HIV antibodies in vitro, in the absence or presence of pokeweed mitogen (PWM). Previous studies showed that up to 20-40% of spontaneously immunoglobulin secreting B cells from HIV+ individuals are HIV-specific. To analyse the frequency of anti-HIV B cells among 'total' peripheral blood B cells in the present study, we used a limiting dilution assay in which EL-4 thymoma cells induce clones of immunoglobulin-secreting cells in activated as well as resting B cells. Anti-HIV B cells were detected not only in 11/12 HIV+ individuals (with frequencies from 1/910 to 1/21,500 B cells cultured; one negative test was from a person undergoing seroconversion), but also in 4/9 HIV- normal blood donors (1/16,200 to 1/49,000 B cells cultured) and in 3/6 newborns from HIV- mothers (1/11,800 to 1/26,600 B cells cultured). The mean frequency was nine times higher in the HIV+ individuals than in the normal donors. As in previous studies, only the cells from HIV+ individuals generated anti-HIV antibodies in PBMC bulk cultures with or without PWM. The relative proportion of specific anti-HIV antibody/total immunoglobulin in PBMC bulk cultures was 800 times higher by the mean than in EL-4 B cell cultures from HIV+ individuals (whereby the total immunoglobulin secretion for equal numbers of B cells cultured was 500 times lower for PBMC). These different results obtained with different assays suggest that in seropositives most anti-HIV B cells belong to an activated B compartment which is quite small, even in a disease with B cell hyperactivity. Therefore, the specific B cells are strongly diluted among the EL-4 cell-responsive, total B cells. On the other hand, the EL-4 assay can detect HIV-reactive B cells in the B cell repertoire of normal, non-infected individuals. PMID- 1733636 TI - LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency. AB - The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-1/ICAM-1 adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD18), but of four MoAbs against the alpha chains (CD11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-1 or ICAM 1 on CVI patients' T cells could not be demonstrated. The accelerated clustering was therefore probably due to an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between B and T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease. PMID- 1733637 TI - Hyper-response of serum IgG1 to Staphylococcus aureus peptidoglycan in patients with hyper-IgE syndrome. AB - The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis and recurrent infections. To determine whether an impairment of the antibody response to Staphylococcus aureus contributes to infections in this syndrome we measured total serum IgG subclass, specific IgG1 and IgG2 levels against peptidoglycan (PG), the immunodominant cell wall component of S. aureus and serum opsonic activity to PG. Of the 14 patients with HIE syndrome, nine had increased level of serum IgG1 and six had IgG2 subclass deficiency. In regard to specific response of IgG1 and IgG2 antibodies to PG, patients were divided into five groups related to ages and compared with 10 control subjects for each age cohort. Patients with HIE syndrome had significant high levels of serum-specific IgG1 to PG and significant decreased levels of serum-specific IgG2 to PG in all five groups. Additionally, serum opsonic activity in patients was significantly higher than that in normal control subjects. It is concluded that IgG2 deficiency or poor IgG2 antibody response to S. aureus is not the explanation of the abnormal susceptibility to S. aureus infections of HIE patients. PMID- 1733638 TI - Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans. AB - Lymphocytes of individuals from a country non-endemic for Leishmania (Sweden), responded with a vigorous interferon-gamma (IFN-gamma) and IL-6 response when exposed to live or dead promastigotes of Leishmania aethiopica. This response was sometimes as strong as when the same cells were exposed to the mitogen (phytohaemagglutinin (PHA)). Furthermore, supernatants of cells exposed to Leishmania promastigotes were able to inhibit the amastigote form of the same parasite. In some few instances there was no such reactivity to Leishmania parasites. It is proposed that most individuals have such a first line cytokine response which is enough to prevent further spread and growth of the parasites. In exposed individuals who display disease symptoms, this non-Leishmania-specific response is overcome (by dose) or is weak (for genetic reasons). In the latter instances curbing of parasite growth would depend on acquired immunity. PMID- 1733639 TI - Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment. AB - Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells. Patients were selected for expression of HLA-A2 and/or HLA-A3 class I transplantation antigen. HLA-restricted cytotoxicity specific for env, gag and nef HIV proteins was quantified for each patient at 6 week intervals. The data clearly indicated that zidovudine has a beneficial effect on the CTL response during the first 6-12 weeks of treatment, inducing cytotoxicity levels up to 100-fold stronger than base line. This effect was usually short lived. However, patients who maintained strong levels of cytotoxicity had better clinical and survival outlook than patients who had lost all detectable cytotoxic lymphocytes. It is proposed that AZT, among other effects, delays the onset of disease in HIV-infected patients by contributing to the stimulation of the HIV-specific CTL response. PMID- 1733640 TI - Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression. AB - The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS. PMID- 1733641 TI - Immunization of mice with mycobacterial culture filtrate proteins. AB - Culture filtrate proteins were obtained from Mycobacterium tuberculosis cultures after 7 days growth in Proskauer and Beck medium. The protein yield increased substantially to peak about the time the number of viable organisms reached its maximum level (day 8). Examination of the protein concentrate by SDS-PAGE revealed the presence of at least 12 separate protein bands varying from 10 to 90 kD. Mice were injected subcutaneously with 20 micrograms of M. tuberculosis culture filtrate (MTCF) protein suspended in saline or Freund's complete or incomplete adjuvant. The vaccinated mice were subjected to an aerogenic challenge with 10(3) colony-forming unit (CFU) M. tuberculosis Erdman and a significant reduction in the number of viable organisms was observed in the spleens and lungs determined over a 21-day period compared with age-matched normal controls. Mice immunized with the same culture filtrate proteins bound to nitrocellulose particles also showed some resistance to the virulent challenge, suggesting that individual antigens present in the culture filtrate were able to induce a protective T cell-mediated immune response in appropriately immunized mice. PMID- 1733642 TI - Rate of metastasis from C3H mouse mammary tumours. AB - Transplants from the same C3H mouse mammary tumour have been used for radiobiological experiments with curative intent for more than 8 years. During that time, the rate of metastasis to the lungs has varied between 0 and 63% and an explanation has been sought for this change. The results of immunological assays showed no obvious pattern. An inverse relationship was found between tumour latency and metastasis. PMID- 1733643 TI - Metastatic mode of gastric carcinoma by flow cytometric and clinicopathologic parameters. AB - We used flow cytometric and conventional clinicopathologic parameters to analyse the metastatic mode of cancer in 113 stomach cancer patients. Liver metastasis was frequent in cases with intestinal-type cancer, cancer located in the distal stomach, positive venous invasion and aneuploid cancer. Lung and pleural metastasis (excluding nodular lung metastasis), however, were frequent in cases with serosal invasion and diploid cancer. Peritoneal metastasis was frequently seen with tumors located in the proximal or whole stomach, diffuse-type cancer and cancer with serosal invasion. All cases developing bone metastasis were positive for lymph node metastasis. DNA ploidy was partially related to the metastatic mode of stomach cancer, but this was not the sole parameter for predicting metastasis. However, prediction may be possible if based on both DNA ploidy and clinicopathologic parameters, suggesting the possibility of the prophylaxis of recurrence by appropriate postoperative adjuvant therapy. PMID- 1733644 TI - Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production. AB - The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases. PMID- 1733645 TI - Myeloma affects both the growth and function of human osteoblast-like cells. AB - Myeloma behaves differently to other osteolytic tumours which metastasize to bone, in that the latter usually provoke reactive bone formation in the host bone. A previous study showed that a myeloma cell line (GM1500) secreted an osteoblast-inhibiting factor(s). The present study was undertaken to determine whether other myeloma cells also secreted a factor(s) which inhibited both cell proliferation and DNA synthesis of osteoblast-like cells and whether the myeloma also affected the function of osteoblasts. The results showed that a second cell line (Karpas 707) as well as myeloma tissue taken from two patients had a similar effect. The myeloma cells did not affect total collagen or protein synthesis, and did not affect the overall degree of mineralization. A biphasic effect was seen on alkaline phosphatase activity. Thus, although the proliferation of the pre osteoblast was affected, the synthetic functions of the osteoblasts were not. PMID- 1733646 TI - Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides. AB - We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05-0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P less than 0.05). However, the tetrapeptide Arg-Gly Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients. PMID- 1733648 TI - Retinoic acid-induced inhibition of metastatic melanoma cell lung colonization and adhesion to endothelium and subendothelial extracellular matrix. AB - The effect of pretreatment of metastatic B16 melanoma cells with 10(-6) M all trans-retinoic acid resulted in a significant inhibition of lung colonization following injection of 10(5) cells into the tail vein of syngeneic C57BL mice. Adhesion of melanoma cells to vascular endothelial cell monolayers, and subendothelial extracellular matrix was also inhibited by pretreatment with retinoic acid, as was tumour cell aggregation following seeding of pretreated cells on to 0.5% agar. Release of 35SO4 from radiolabelled subendothelial extracellular matrix by melanoma cells was essentially unaltered by retinoic acid pretreatment, as was the release of radiolabel from [3H]proline-labelled matrix, while plasminogen activator activity was enhanced in retinoic-acid-treated cells. These observed changes in adhesive properties may be responsible, at least in part, for the retinoic-acid-induced inhibition of lung colonization. PMID- 1733647 TI - Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin). AB - We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor conditioned medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from tumor cells. PMID- 1733649 TI - Effects of size and growth time of a murine sarcoma on its metastatic spread. AB - The effects of the size of an implanted tumor and of its time of growth on metastasis were examined in the same tumor grown under two different conditions. Tumors were implanted either in the untreated legs of mice or in legs that had been irradiated one day earlier. The radiation slowed the growth of tumors. When the tumors grew to predetermined diameters, the legs were excised and 20 days later the mice were examined for the presence of lung metastases. Equal changes in the time to excision of the tumors grown under the two conditions led to nearly equal changes in the proportions of animals with metastases. Tumor volume effects were not apparent in this consideration of changes in metastasis rates with time. This work reanalyses the data of that study using the variability in growth rates within a tumor growth condition to investigate the effect of tumor size on metastatic intensity. This intensity increased at least linearly with tumor volume for both irradiated and control animals. The finding of equal effect at equal growth times of the implanted tumors under the two growth conditions was confirmed but is due to: (1) metastatic intensity changing five times as rapidly with tumor size in the irradiated group as compared to the control group and (2) non-exponential retarded growth of the tumors in the control treatment group. PMID- 1733650 TI - Policy on HIV infected physicians adopted by CMS Board. PMID- 1733651 TI - Occupational health and environmental illnesses in Colorado. PMID- 1733652 TI - Death certificates--fill them out carefully (and correctly). PMID- 1733653 TI - Assistance for AIDS Specific Drugs (AASD) Program. PMID- 1733654 TI - Iatrogenic (intraoperative) rubber glove allergy and anaphylaxis: Part I. PMID- 1733655 TI - A dermatologic diary. Portrait of a practice. PMID- 1733656 TI - Chronic varicella zoster in a child infected with human immunodeficiency virus: case report and review of the literature. AB - Chronic zoster represents an infrequent presentation of varicella zoster virus infection. It is observed with increased frequency in patients infected with human immunodeficiency virus, especially when their lymphocyte counts are depressed. We report a child infected with human immunodeficiency virus who showed a long-standing cutaneous zoster lesion and was treated for a prolonged period of time with acyclovir. The occurrence of resistance to acyclovir by varicella zoster virus was suspected based on the clinical picture. The clinical and laboratory features of this case and a review of the literature are presented. PMID- 1733657 TI - Skin reactions to radiotherapy--a spectrum resembling erythema multiforme: case report and review of the literature. AB - Eruptions resembling erythema multiforme associated with radiotherapy are rare. Although several case reports are cited in the older literature, only recently has this phenomenon been described in patients receiving external beam radiation therapy both with and without contributory concurrent medications. The eruption typically begins within the radiation port and then generalizes; it is usually self-limited, but serious and fatal outcomes are reported. We review the literature and report a case of an eruption resembling erythema multiforme associated with external beam irradiation and 5-fluorouracil. PMID- 1733658 TI - Basal cell carcinoma and melanocytic nevus in the same lesion. AB - We report a case of basal cell carcinoma and intradermal melanocytic nevus in the same lesion. A review of the literature indicates that the simultaneous occurrence of two or more neoplasms in one specimen is a relatively infrequent finding. The pathogenesis of simultaneously occurring neoplasms remains the subject of speculation. Based on currently available evidence, we believe that the coexistence of lesions in this particular patient is most likely coincidental. PMID- 1733659 TI - Dermatology days, 1991: Ocean City, Maryland. PMID- 1733660 TI - Secondary syphilis presenting as cutaneous nodules in a patient previously treated for laryngeal carcinoma. AB - A person who had previously been treated for laryngeal carcinoma presented with the new onset of asymptomatic nodular skin lesions. The preliminary differential diagnosis included cutaneous metastasis. Examination of a biopsy specimen of the lesions and results of subsequent laboratory investigation ruled out the possibility of recurrent metastatic disease and established a diagnosis of secondary syphilis. The differential diagnosis of nodular lesions that resemble a lymphoid neoplasm or a cutaneous metastasis in a patient treated for cancer should also include secondary syphilis. PMID- 1733661 TI - Delayed reaction to suture material simulating melanoma. AB - A twenty-one-year-old woman who had been involved in an accident sustained severe trauma to the left side of her face and scalp. Because of deterioration in her neurologic condition, a number of exploratory burr holes were drilled in her skull. Fifteen years later, a 6 mm black tender nodule was noted on the left temple, close to one of the burr holes. Nodular melanoma was suspected, but results of microscopic examination proved the lesion to be a granuloma with transepidermal elimination of exogenous filamentous material. The relationship between foreign bodies and cutaneous neoplasia, genuine or simulated, is noted briefly. PMID- 1733662 TI - Mobile encapsulated lipomas. AB - Mobile encapsulated lipomas are a benign neoplastic process with pronounced mobility in the subcutaneous plane. Characteristic clinical and histologic features differentiate this distinctive entity from similar reactive adipose processes. PMID- 1733663 TI - Microtubule-associated proteins during mouse spermatogenesis: localization of a protein immunologically related to brain MAP1B protein in the synaptonemal complex. AB - Monospecific polyclonal antibodies against MAP1A protein and an immunologically related brain MAP1B polypeptide were used to visualize mouse synaptonemal complexes (SCs) with immunofluorescence microscopy. Anti-MAP1A antibody recognized SCs uniformly. However, when anti-MAP1B antibody was used, a dashed pattern of staining was observed along the SCs in both autosomes and pachytene XY bivalents. After purification of SCs, immunoblots of the electrophoresed proteins revealed a polypeptide of 220 kDal, which was recognized by anti-MAP1B antibody, and two proteins of 180 kDal and 160 kDal, which were recognized by anti-MAP1A antibody. High-molecular-weight polypeptides immunologically related to microtubule-associated proteins were localized in the cell nucleus. The function of these nuclear proteins is unknown. The distribution of fluorescent signal corresponding to the 220-kDal protein during meiosis and spermiogenesis and its localization in the nuclear matrix suggest the participation of preexisting nucleoskeletal proteins in the molecular organization of the SC and its dynamics during meiotic prophase. PMID- 1733664 TI - Detection of structural chromosome aberrations in immunophenotyped mitoses. AB - The recently developed MAC (morphology-antibody-chromosome) method allows simultaneous immunophenotype and karyotype analysis in the same cell. To date, application of this new method has been hampered by the poor quality of chromosome banding. In this paper, we describe a modified simultaneous immunofluorescence and Q-banding technique, as well as a new combination of immunohistochemical and fluorescent R-banding methods. By further modifying the MAC method, we were able not only to achieve unequivocal results with weakly expressed antigens but also to improve the quality of the banding techniques, so that even structural chromosome abnormalities were well defined. PMID- 1733665 TI - Isolation and comparative mapping of a human chromosome 20-specific alpha satellite DNA clone. AB - We have isolated and characterized a human genomic DNA clone (PZ20, locus D20Z2) that identifies, under high-stringency hybridization conditions, an alphoid DNA subset specific for chromosome 20. The specificity was determined using fluorescence in situ hybridization. Sequence analysis confirmed our previously reported data on the great similarity between the chromosome 20 and chromosome 2 alphoid subsets. Comparative mapping of pZ20 on chimpanzee and gorilla chromosomes, also performed under high-stringency conditions, indicates that the alphoid subset has ancestral sequences on chimpanzee chromosome 11 and gorilla chromosome 19. However, no hybridization was observed to chromosomes 21 in the great apes, the homolog of human chromosome 20. PMID- 1733666 TI - The polymorphic DNA sequence D20S14 is assigned to human chromosome 20p12--- p11.2 by in situ hybridization. AB - The polymorphic DNA marker D20S14 was previously mapped to human chromosome 20 and shown to be linked to two other DNA markers, D20S5 and D20S6, located at 20p12. This segment has been implicated in several human diseases. Because of its importance, we mapped the D20S14 locus to 20p12----p11.2 by radioactive in situ hybridization. PMID- 1733667 TI - Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. AB - Using in situ hybridization and a panel of human X rodent somatic cell hybrids, which discriminates between four different regions of human chromosome 22, we have localized the gene for human platelet-derived endothelial cell growth factor (ECGF1) to 22q13, placing ECGF1 distal to the PDGFB locus at 22q12.3----q13.1. PMID- 1733668 TI - Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter. AB - The structural gene for human kininogen (KNG) was localized to chromosome 3q26--- qter by in situ hybridization. The assignment substantiates the evolutionary relationship of kininogen to two other members of the cystatin superfamily, alpha 2-HS-glycoprotein and histidine-rich glycoprotein, which also map to chromosome 3. PMID- 1733669 TI - A physical and genetic linkage map of the distal long arm of human chromosome 5. AB - By in situ hybridization of probes for three cloned genes and eight genetically linked polymorphic DNA markers, we have prepared a physical map of the distal long arm of chromosome 5. These results, together with the localizations of 11 genes and the genetic linkage map reported previously by us and by other investigators, represent a map that spans 55 cM. PMID- 1733670 TI - Cytogenetics and karyosystematics of South American oryzomyine rodents (Cricetidae: Sigmodontinae). IV. Karyotypes of Venezuelan, Trinidadian, and Argentinian water rats of the genus Nectomys. AB - Bone marrow chromosomes were studied in South American water rats of the genus Nectomys from Venezuela, Trinidad, and Argentina. Specimens of N. squamipes from western and southern Venezuela showed a 2n = 52-53 karyotype, whereas a 2n = 56 57 karyotype was found in specimens from northeastern Argentina. In both cases, odd karyotypes can be explained by the presence of a supernumerary chromosome. In contrast, water rats from northeastern Venezuela and Trinidad showed a strikingly reduced 2n = 16-17 polymorphic chromosome complement. Six different karyomorphs were found among the latter, which may have resulted from a combination of pericentric inversions in two pairs of autosomes and a centromeric fusion in another autosomal pair. It is proposed that the new 2n = 16-17 cytotypes belong to a species of its own, for which the name N. palmipes is suggested. PMID- 1733671 TI - Defective repair of radiation-induced chromosomal damage in scid/scid mice. AB - The murine severe combined immunodeficiency (scid) mutation interferes with normal recombination of immunoglobulin and T-cell receptor genes. This immunologic defect results in a lack of fully differentiated B and T cells in scid/scid mice. Animals homozygous for the scid mutation also display increased sensitivity to the damaging effects of ionizing radiation. We report here our observations of high frequencies of radiation-induced chromatid interchanges and intrachanges in bone marrow cells and fibroblasts from scid/scid mice. The presence of these aberrant chromosome structures suggests that a delay in strand rejoining underlies the increased sensitivity of scid/scid mice to ionizing radiation. The scid mutation may provide important clues for understanding the relationship between mitotic recombination and DNA repair in higher eukaryotic cells. PMID- 1733672 TI - Assignment of two markers carried by human chromosome 1 to different cattle synteny groups: FH to U1 and PEPC to U17 (chromosome 8). AB - Two loci located on human chromosome 1 were mapped in cattle by means of interspecific (hamster x cattle) somatic cell hybridization. FH is assigned to the U1 synteny group together with PGD, ENO1, AT3, and REN, while PEPC is found to belong to the U17 group (chromosome 8), like FN1, CRYG, and VIL1. PMID- 1733673 TI - Localization of the pig luteinizing hormone/choriogonadotropin receptor gene (LHCGR) by radioactive and nonradioactive in situ hybridization. AB - The porcine gene for luteinizing hormone/choriogonadotropin receptor (LHCGR) was localized to chromosome 3q2.2----q2.3 using radioactive and nonradioactive in situ hybridization. A computer-assisted image-analysis system was developed which facilitated detection of the position of silver grains and fluorescent spots on the chromosomes after in situ hybridization. Compared with autoradiographic visualization, the nonisotopic procedure proved to be more rapid, precise, and highly specific; however, nonradiographic in situ hybridization was much less efficient than the autoradiographic technique for the detection of unique DNA sequences with small probes. From these results and published gene-mapping data, it was concluded that the synteny between LHCGR and MDH1 observed in man is conserved in the pig genome. PMID- 1733674 TI - Equalization of Z and W axes in chicken and quail oocytes. AB - The different morphological types of ZW pairs have been classified in three main types according to the relative extension of the free segment of the Z axis: 1, "long asynaptic segment;" 2, "medium asynaptic segment;" and 3, "equalized." Pre- and post-pairing types have also been defined. Frequencies of each type were determined at day 20 and day 21 of incubation, and one and three days after hatching. The changing frequencies and the morphological transitions observed show a definite sequence of ZW types that can be used as a timetable for pachytene substaging. Measurements made on each ZW type show that the Z axis of the chicken shortens from 20.6 microns to 13.1 microns. This shortening occurs both in the free segment (at a higher rate) and in the paired segment (at a lower rate). The synaptonemal complex becomes elongated while adjustment occurs. The equalized Z axis makes many twists around the W axis. However, a segment 1 micron long from the synaptic terminus is free from twists and is assumed to be the homologously paired region. The ZW pair of the quail shows a similar behavior but equalization of the Z and W axes ends earlier and forms a straighter synaptonemal complex as compared with the chicken. In both species a recombination nodule is strictly localized near the synaptic terminus. In the ZW pair of the quail the average location of this nodule is 0.14 microns from the synaptic terminus. The meiotic behavior of ZW pairs in birds may be conserved. PMID- 1733675 TI - Mapping of five human chromosome 19 DNA markers to owl monkey chromosomes. AB - Hybridization of DNA from three panels of karyotypically distinct owl monkey x rodent somatic cell hybrids with human DNA probes resulted in the syntenic assignments of INSR-LDLR-TGFB1-APOE-D19S8 to owl monkey chromosome 25 of karyotype VI (2n = 49/50), INSR-LDLR-TGFB1-D19S8 to chromosome 2 of karyotype II (2n = 54), and INSR-APOE to chromosome 2 of karyotype V (2n = 46). The APOE and D19S8 loci are on adjacent regions proximal to the centromere of chromosomes 25q (K-VI) and 2p (K-II), as determined by in situ chromosomal hybridization analysis. These findings support our previous proposals on (1) the homology of these chromosomes of three owl monkey karyotypes, (2) the evolutionary derivation of chromosome 2 of karyotypes II and V as the result of two separate centric fusion events, and (3) the likelihood that owl monkey chromosome 25 (K-VI) (and its homologs) is a conserved genetic homoeolog of human chromosome 19. PMID- 1733676 TI - Telomeric signals in robertsonian fusion and fission chromosomes: implications for the origin of pseudoaneuploidy. AB - In situ hybridization with synthetic plant telomeric sequences resulted in labeling of all broad bean (Vicia faba) chromosomes at their ends only. Telocentric chromosomes derived by fission of the metacentric satellite chromosome of V. faba also showed signals at both of their ends, whereas the ancestral metacentric did not display signals at its primary constriction, the point of fission. As in V. faba, all acrocentric mouse chromosomes were labeled by in situ hybridization with a vertebrate telomeric probe at both ends of each chromatid exclusively. However, different metacentric Robertsonian chromosomes derived by fusion of defined acrocentrics did not show signals at their primary constrictions. The mechanism of Robertsonian rearrangement leading to a pseudoaneuploid increase or decrease in chromosome number therefore cannot consist solely of a simple fission or fusion of chromosomes without a concomitant gain or loss of chromatin material. The additional assumption of a subdetectable deletion of telomeric sequences after fusion and amplification of these sequences following fission is necessary to explain the present observations. PMID- 1733677 TI - Mapping of the porcine lipoprotein lipase (LPL) gene to chromosome 14q12----q14 by in situ hybridization. PMID- 1733679 TI - TNM staging system. PMID- 1733678 TI - Outpatient protocol for biofeedback therapy of pelvic floor outlet obstruction. AB - Pelvic floor outlet obstruction is a rare cause of severe constipation. Anal myectomy, subtotal colectomy, and medical therapy have limited success. The purpose of this study was to develop a short outpatient treatment using biofeedback techniques. Nine patients with severe constipation and straining resulting from pelvic floor outlet obstruction underwent complete investigation of the pelvic floor musculature and anal sphincter mechanism. Patients were unable to expel a 60-cc rectal balloon and had nonrelaxing puborectalis on defecography. The treatment protocol utilized anal surface electromyography to document improper straining and retrain pelvic floor muscles to relax during defecation. Sensory retraining with a rectal balloon, behavioral relaxation techniques, and defecation of simulated stool using a 120-cc Metamucil (Procter & Gamble, Cincinnati, OH) slurry in the rectum allowed re-establishment of normal defecation in all nine patients. Repeat training was required in three patients during follow-up. Treatment of pelvic floor outlet obstruction with outpatient retraining techniques is possible. PMID- 1733680 TI - Preoperative radiation therapy for locally advanced carcinoma of the rectum. Clinicopathologic correlative review. AB - During a three-year period, 27 patients with the diagnosis of adenocarcinoma of the rectum were referred to the Department of Radiation Oncology and accepted for preoperative radiation therapy. The referral was based solely on endoluminal ultrasound staging (ELUS) of an unfavorable lesion (n = 12) or ultrasound staging with the clinical impression of a fixed (n = 9) or tethered (n = 6) lesion. High dose (4,500-5,600 cGy) preoperative radiation was followed by definitive surgery in four to seven weeks. The gross and microscopic pathology observed in 23 specimens of this group of patients formed the basis of this report. The microscopic findings that persist after radiation allow an accurate determination of the tumor stage existing prior to radiation. Correlations are made between the original evaluation of the tumor, including ELUS, and the microscopic findings. ELUS accurately predicted the depth of tumor penetration in 20 to 23 of 23 specimens and the lymph node status in 16 of 23 specimens. In the context of the pathologic findings as described, downstaging was not demonstrated. Following this radiation protocol, a marked reduction in tumor mass was demonstrated, as well as evidence of tumor destruction in the remaining mass, varying from minimal to total elimination of viable tumor. The concept that radiation fibrosis exists only as it approximates or replaces neoplasm is offered. In the context of this pathologic finding, improved resectability occurred for certain tumors. It is recommended that ELUS be added to the clinical evaluation of rectal adenocarcinoma. It is also recommended that the pathologic findings described be used when reporting the stage of rectal tumors that have received high-dose preoperative radiation therapy. PMID- 1733681 TI - Gallstones and colorectal cancer--there is a relationship, but it is hardly due to cholecystectomy. AB - The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship. PMID- 1733682 TI - Colectomy-proctomucosectomy with S-pouch: operative procedures, complications, and functional outcome in 69 consecutive patients. AB - Sixty-nine patients were operated upon in a three-stage procedure. Early complications occurred in 29 percent after colectomy-ileostomy, in 25 percent after proctomucosectomy with ileoanal anastomosis and loop ileostomy, and in 9 percent after closure of loop ileostomy. Only three of these were considered serious. Seventy-one percent of the patients were readmitted into the hospital between the three operations or after the last one. Total hospital stay was 49 days (median); the range was 20 to 345 days. Reconstruction of the reservoir was performed in four patients owing to defecation problems, with satisfying functional results in two patients, while two emptied by catheter. There was no postoperative mortality or pelvic sepsis, and no pouches were excised. Ileostomy was re-established in two patients. At histopathologic re-evaluation of colectomy specimens, the diagnosis was changed from ulcerative colitis to Crohn's disease in three patients and to indeterminate colitis in five. Median follow-up was 4.3 years. Continent anal defecation without ileostomy was achieved in 67 patients (97 percent), with 4.1 bowel movements per day and 0.6 per night. Perfect continence was achieved in 55 percent in the daytime and in 43 percent at night. The low rate of reservoir-threatening complications is attributed to the three stage procedure and the technical details in the surgical procedures. PMID- 1733683 TI - Abdominal rectopexy for complete prolapse: prospective study evaluating changes in symptoms and anorectal function. AB - The effect of abdominal rectopexy on bowel function is difficult to assess in retrospective studies because preoperative bowel habit cannot be determined accurately. This study examined bowel symptoms and physiologic tests of anorectal function prospectively in 23 patients before and at three months after rectopexy. Rectopexy eliminated complete prolapse in all and stopped bleeding in 16 of 18 patients. Incontinence improved significantly. Constipation (less than 3 bowel actions per week or straining for more than 25 percent of defecation time) was relieved in 4 of 11 affected patients but developed in 5 of the 12 who were not constipated preoperatively. Since the median bowel frequency was 21 motions per week before surgery and 17 afterward, the main determinant of constipation was straining. Abdominal pain was relieved after rectopexy in 6 of 12 patients but developed in 3 of 13 who were pain-free before surgery. Three patients (13 percent) had a first-degree relative with rectal prolapse. Perineal descent decreased significantly. Maximal anal resting pressure increased significantly, but this did not correlate significantly with improved continence. Twenty-one patients (91 percent) could expel a 50-ml balloon preoperatively; 18 of those 21 could still do so postoperatively. The two patients who could not expel the balloon preoperatively were able to do so postoperative. This study shows that rectal prolapse is associated with profoundly abnormal defecation and abdominal pain. While abdominal rectopexy improved continence, it may improve or worsen other bowel symptoms, including constipation. PMID- 1733684 TI - Is anorectal surgery on chronic dialysis patients risky? AB - Patients on chronic hemodialysis for end-stage renal disease (ESRD) may develop anorectal problems necessitating surgery. From January 1984 to December 1987, 18 ESRD patients underwent anorectal surgery. During this period, a mean of 215 patients underwent dialysis. Patients with ESRD present with characteristic problems: chronic constipation, need for dialysis pre- and postoperatively with heparin infusion, anemia, anticoagulation secondary to the consequences of uremia, and significant medical problems including coronary artery disease, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD). Two patients had concomitant anal fissure, two had fistula-in-ano, and one had an acute perianal abscess. In two patients, the postoperative course was complicated by hemorrhage and, in one patient, by abscess formation. There was no delay in wound healing compared with a cohort group. The essentials of perioperative management are discussed with respect to timing of dialysis, methods of anesthesia and pain management, coagulation screening, and complications. Patients on well-managed chronic dialysis will tolerate anorectal surgery without undue jeopardy. PMID- 1733685 TI - Anal sphincter imaging in fecal incontinence using endosonography. AB - Clinical anal examination, manometry (resting and squeeze pressures), and single fiber electromyography were compared with endosonography of the anal sphincters in 14 patients with fecal incontinence. Technical aspects of the procedure and normal imaging of the puborectal muscle and both sphincters were defined. Defects in both sphincters were seen in nine patients. The defect is visualized as a clear discontinuity in the muscular ring. Compared with the conventional studies, anal endosonography gave significant information in six patients (four male patients after perianal surgery and two women), showing sphincter defects in five patients and integrity of the sphincters in another one. This information obtained by endosonography was important in understanding the type and extension of the lesion and deciding upon the surgical repair. Anal endosonography is an imaging technique of the sphincters that can assess their integrity in fecal incontinence. PMID- 1733686 TI - Volvulus of the sigmoid colon in Jordan. AB - This report discusses 27 patients with sigmoid volvulus treated at Jordan University Hospital (JUH) during a 15-year period. These patients represented 4.7 percent of adult patients treated for intestinal obstruction in the same period. The average age was 54.5 years, and none of the patients was institutionalized. Twenty-five patients presented with acute symptoms, and two had chronic symptoms. Sigmoidoscopic detorsion was achieved in 15 patients. Emergency resection was required in two of these patients: for the development of gangrene a few hours after detorsion in one patient and for recurrence within 24 hours in the other despite the presence of a rectal tube. Early recurrence occurred in two other patients and was managed endoscopically. Emergency surgery was performed in 10 other patients: for a failed endoscopic detorsion in three patients, for ulcerated and bleeding mucosa forecasting gangrene in another, and as a primary treatment in six patients who were either misdiagnosed or suspected to have gangrenous bowel. Elective resection was performed in 13 patients. The mortality rate was 15 percent (4/27) for the whole series and 33.3 percent (1/3) for those with gangrenous bowel. PMID- 1733687 TI - Straight ileoanal anastomosis after longitudinal strip myectomy in the swine model. AB - In an attempt to improve the function of the straight ileoanal anastomosis, an experimental study was performed using the swine model. The terminal ileum was altered by completely removing two longitudinal strips of muscle prior to performing a straight ileoanal anastomosis. The intent of the study was to determine whether muscle stripping was technically possible and whether bowel thus treated would remain viable to passively form a pelvic reservoir. The length of time required for formation of the reservoir was noted. All animals survived the procedure to allow evaluation. The muscle stripping was not difficult to perform. Viability was not a problem since the myectomy animals thrived well and demonstrated continence, weight gain, and reservoir formation. The results are encouraging. It appears that strips of muscularis propria can be removed from the terminal ileum without jeopardizing its viability. This seems to disrupt sufficiently the tonus of the bowel to allow better function of the straight ileoanal anastomosis through formation of a passive pelvic reservoir within a month's time in the swine model, and it may have application in the human. PMID- 1733688 TI - Massive lower gastrointestinal hemorrhage caused by pseudocyst of the pancreas ruptured into the colon. Report of two cases. AB - We report two cases of massive lower gastrointestinal (LGI) bleeding occurring in young adult men, as the first manifestation of pseudocyst of the pancreas. Despite the rarity of such a complication, pancreatic pseudocyst should be kept in mind as a possible source of massive LGI bleeding requiring immediate surgical treatment. PMID- 1733689 TI - Split notochord syndrome in an adult presenting with colonic duplication. Report of a case. AB - A case of tubular colonic duplication, sigmoid colon diverticulum, and lumbar anterior spina bifida in a 28-year-old man was diagnosed as split notochord syndrome. After subtotal colectomy, including the duplicated colon, the patient recovered. Histologic study of the duplicated colon revealed multifocal, ectopic gastric fundic mucosa in a mosaic pattern. Since bleeding and perforation occur most frequently in conjunction with ectopic gastric mucosa within the duplication, we believe that complete resection of the duplicated bowel is the best procedure. Split notochord syndrome is a rare congenital anomaly. It is usually discovered in the first year of life, and the majority of reported cases have involved the cervical or thoracic region. Our patient is exceptional in having reached the age of 28 years without complaints and in that his case involved lumbar anterior spina bifida and tubular colonic duplication. PMID- 1733690 TI - Anorectal pressure gradient in patients with anal incontinence. AB - Anorectal pressures in patients with fecal incontinence have been investigated. With anal manometry, 34 percent of patients with fecal incontinence had maximal resting pressure and 39 percent had maximal squeeze pressure within the normal range. When a pressure gradient was calculated as the pressure difference between maximal resting pressure and rectal pressuring during filling of a rectal balloon, patients with fecal incontinence could be better distinguished from controls: 20 percent of patients with fecal incontinence had values within the normal range when the rectal pressure at the earliest defecation urge was used (P less than 0.05), and 12 percent had values within the normal range when the rectal pressure at maximal tolerable volume was used (P less than 0.01). Anorectal pressure gradient measurements seem to distinguish patients with fecal incontinence from controls better than maximal resting pressure or maximal squeeze pressure alone. PMID- 1733691 TI - Technique for revision of continent ileostomy. AB - A technique is described for revising an incompetent nipple valve of a continent ileostomy. The procedure involves preserving the incompetent valve and using it as a collar around the base of the new valve to improve function. PMID- 1733692 TI - Hemorrhoidectomy with self-retaining retraction. AB - Hemorrhoidectomy is facilitated by good exposure. Appropriate application of towel clips helps to maintain good exposure during hemorrhoidectomy. PMID- 1733693 TI - Intersphincteric surgical access to the rectum for the treatment of villous adenomas. AB - Intersphincteric surgical access is proposed to treat villous adenomas of the posterior rectal wall, not accessible to an endoanal approach, in which anterior resection is not suitable because of the poor general condition of the patient. PMID- 1733694 TI - Flow cytometric analysis of DNA content in colorectal carcinoma. AB - Over the past decade, flow cytometric DNA analysis has been employed by a number of investigators in an attempt to further define patient prognosis beyond classic pathologic staging. The results of these studies taken independently have been confusing; however, their cumulative effect suggests that flow cytometry is a useful prognostic indicator and can be used to further delineate prognosis within a specific pathologic stage. DNA nondiploid tumors are more likely to recur than diploid tumors, and patients with DNA nondiploid tumors have a poorer five-year survival than patients with DNA diploid tumors. There appears to be a weak relationship between advanced pathologic stage and DNA aneuploid tumors, although there is no clear and consistent relationship between tumor ploidy and histology. Therefore, all patients with colorectal tumors should undergo DNA ploidy analysis. Patients with DNA nondiploid tumors should be treated for biologically more aggressive disease independent of other prognostic variables. Ploidy status should be employed as a variable by which to randomize patients to both primary treatment schemes and adjuvant therapies in clinical trials. PMID- 1733695 TI - [The long-term toxicity of polychemotherapy in successfully treated testicular carcinoma]. AB - Of 55 patients with testicular cancer, treated by combination chemotherapy including cisplatin, 21 (mean age 35 [21-51] years) were reexamined for late sequelae of the chemotherapy 1-9 years later. No patient had a recurrence or second malignancy. They all had normal renal function (renal sequence scintigraphy; creatinine clearance). Seven of 20 patients had a polyneuropathy, nine of 18 had high-tone hearing loss. Two patients became fathers after treatment. In nine of 20 patients the serum concentration of follicle-stimulating hormone was raised to above 20 mU/ml, evidence of germ-cell damage. Six of 13 patients had an abnormal ejaculation following retroperitoneal lymphadenectomy or excision of a residual tumour. There was no evidence of any life-limiting toxicity of the chemotherapy. PMID- 1733696 TI - [The percutaneous implantable heart-lung machine in the coronary angioplasty of high-risk and emergency patients]. AB - Using a recently developed, percutaneously introduced cardiopulmonary support system (PCPS) seven high-risk patients (four men, three women; mean age 61 [41 77] years) underwent percutaneous transluminal coronary angioplasty. In one patient, with unstable angina and in incipient cardiogenic shock, perfusion with PCPS was begun immediately before coronary angioplasty. In six patients it was undertaken with the PCPS on stand-by, but eventually not needed. Coronary angioplasty was successful in six patients, partially successful in one. Angina was considerably improved long-term in all patients, but one of them died 2.5 months afterwards at home. In two other patients (men, aged 41 and 71 years) with acute myocardial infarction, the PCPS was employed under circumstances of emergency resuscitation. In both cases recanalization of the occluded coronary artery was achieved mechanically during perfusion with PCPS; one patient survived. Availability of PCPS, also in an emergency, makes it possible to extend the indications for coronary angioplasty to include even high-risk patients. PMID- 1733697 TI - [Taenia crassiceps infection in AIDS]. AB - A 33-year-old patient with AIDS, and a history of episodes of Pneumocystis carinii pneumonia and cerebral toxoplasmosis, developed a subcutaneous paravertebral infiltrate, which at first resembled a haematoma. Over a period of several weeks, the lesion spread to cover almost the entire back. Initially, numerous investigations failed to reveal the aetiology. His general condition worsened progressively, and intermittent bleeding into the soft tissue of the back occurred, requiring transfusion. This was associated with the development of an isolated deficiency of clotting factor V and a fall in Quick values to 10%. On the 22nd day after admission, the infiltrate ruptured spontaneously, releasing blood and a large number of whitish spherical masses 2-3 mm in diameter. These were identified as Cysticerci longicolles, the larval form of Taenia crassiceps, a tapeworm occurring in Canidae. The blood clotting values returned to normal within two days of incision of the infiltrate and commencement of therapy with mebendazole (6 g/day) and praziquantel (3.6 g/day). The infiltrate subsequently regressed almost completely. After combination treatment for 2 weeks, treatment was continued with praziquantel alone, which, however, the patient stopped himself after 10 weeks. A recurrence at the same site 4 months later was successfully treated with a further course of mebendazole and praziquantel. PMID- 1733698 TI - [The diagnosis of corrosive esophageal burns]. PMID- 1733699 TI - [Nonpharmacological factors in the treatment of arterial hypertension. The roll of obesity, alcohol consumption and table salt intake]. PMID- 1733700 TI - [The history of massage]. PMID- 1733701 TI - [The safekeeping of medical data on employment medical exams]. PMID- 1733702 TI - [The x-ray diagnosis of diverticulosis]. PMID- 1733703 TI - [Mechanical heart valves or bioprostheses. A 12-year comparison]. PMID- 1733704 TI - Effects of stage of the cycle and estradiol-17 beta on oxytocin synthesis by ovine granulosa and luteal cells. AB - Individual ovine follicles or corpora lutea (CL) were obtained at different stages of the estrous cycle to compare the pattern of oxytocin synthesis with time in vitro. Granulosa cells from follicles in the early follicular phase produced minimal amounts of oxytocin whereas output from preovulatory (post LH surge) follicles increased to a peak of 540 pg/10(4) cells.24 h on days 4-7 in vitro declining to 180 pg/10(4) cells.24 h by day 11. Production from day 1 CL was also high, peaking at 1639 pg/10(4) cells.24 h. In contrast the capacity for oxytocin synthesis by day 2 CL had already declined, with peak output reaching only 185 pg/10(4) cells.24 h on days 3-4. Day 9 CL produced small amounts of oxytocin (50 pg/10(4) cells in the first 24 h) followed by a low output thereafter. The effect of estradiol-17 beta (E2 beta) on oxytocin synthesis was examined. The results were dependent on the stage of the cycle at which the cells were obtained. Oxytocin production was significantly stimulated in three and inhibited in four out of nine preovulatory follicles by the addition of 50 or 500 ng/ml E2 beta, whereas in days 1 and 2 CL E2 beta consistently inhibited oxytocin synthesis and in day 9 CL no response was found. These data indicate that the ovarian capacity to synthesize oxytocin varies markedly at different stages of the cycle, and that cells obtained close to ovulation do not experience the rapid down-regulation in oxytocin synthesis which occurs in vivo in the early luteal phase. E2 beta may switch from having a stimulatory to an inhibitory action on oxytocin synthesis shortly before ovulation. PMID- 1733705 TI - Subgroups of luteinizing hormone-releasing hormone perikarya defined by computer analyses in the basal forebrain of intact female rats. AB - The hypothesis that the basal forebrain population of LHRH perikarya is composed of heterogeneous subgroups was examined in this study. We used three-dimensional computerized reconstruction to examine populations of LHRH-immunopositive neurons detected in noncolchicine treated cycling female rats. Perikarya were detected with two antisera capable of detecting LHRH decapeptide within larger mol wt species, i.e. Millar's (RM) 1076 and Arimura's (AA) 419. No immunopositive perikarya were detected with antiserum AA 422, which requires the fully processed decapeptide for binding. A more broadly distributed population of LHRH neurons was detected in females killed on proestrus than in females killed on estrus or the other days of the cycle. These relationships were observed with both antisera, RM 1076 and AA 419. Subgroups of cells were clearly defined when the population of LHRH neurons detected on proestrus was simultaneously displayed with the population detected on estrus. Strikingly similar subgroups were revealed by simultaneous displays of populations of LHRH neurons detected by the antisera RM 1076 and AA 419 in proestrous females. This study revealed a three dimensional onion skin-like laminar organization of LHRH subgroups expanding from the ventricle outward laterally and from the diagonal band of Broca to the hypothalamus caudally. We propose that these subgroups vary in their metabolic activity of biosynthesis, processing, transport, or release of LHRH in relation to the proestrous preovulatory release of LH. PMID- 1733706 TI - Additive and/or synergistic effects of 5 alpha-dihydrotestosterone, dexamethasone, and triiodo-L-thyronine on induction of proteinases and epidermal growth factor in the submandibular gland of hypophysectomized mice. AB - The effects of androgen, glucocorticoid, and thyroid hormones on levels of proteinase isozymes and epidermal growth factor (EGF) in the submandibular glands of hypophysectomized (Hypox) mice were investigated. Total proteinase activity in males was decreased by hypophysectomy and increased by single or combined injection of the three hormones into these mice. 5 alpha-Dihydrotestosterone (DHT) had the strongest effect, and dexamethasone (Dex) the least. By isoelectric focusing, proteinases extracted from the submandibular gland of untreated male and female mice were fractionated into four isozymes with pI values of 4.8 (proteinase-F), 5.8 (proteinase-D), 6.2 (proteinase-A), and 10.0 (proteinase-P). In Hypox mice (both sexes), there was only a single isozyme, proteinase-F. Proteinase-D, -A, and -P were induced in the submandibular gland of Hypox males by injections of DHT, Dex, and/or T3; the percent ratio of activity of each of these isozymes induced by these hormones, given either singly or in combination, was almost parallel among the three isozymes. Synergistic effects were observed between T3 and Dex, and additive effects between T3 and DHT. The increase in proteinase isozyme activities by concomitant injections of T3 and Dex was about 2 times more than the additive values. The changes in proteinase-F upon hormone injection were complicated. In females, the enzyme activity was decreased by hypophysectomy and increased by DHT administration. In males, on the other hand, it was increased by hypophysectomy and suppressed by T3 or T3 plus steroid hormones. The EGF level in the submandibular gland was decreased to about 1/800th (males) or 1/90th (females) of its normal level by hypophysectomy. Its level in the Hypox animal was greatly increased by all three hormones, given singly or in combination. Synergism was also observed between T3 and steroid hormones; DHT plus T3 and T3 plus Dex induced EGF 6 times and 9 times, respectively, more than the additive values. These values were much greater than those for the induction of proteinase-D, -A, and -P by combined injections of T3 and steroids. The present results suggest that the genes coding for proteinase-A, -D, and -P are located close to each other and that the onset of their expression may be controlled by the same regulatory mechanism. By contrast, the gene for proteinase F may be mapped to a different locus or regulated differently. The mechanism of induction of EGF by T3, DHT, and Dex appears to be similar to but not completely the same as that for proteinase-D, -A, and -P. PMID- 1733707 TI - A mouse growth hormone-binding protein RIA: concentrations in maternal serum during pregnancy. AB - A RIA for mouse growth hormone-binding protein (mGHBP) was developed. A 28-amino acid synthetic peptide corresponding to the carboxyl-terminal 27 amino acids of mGHBP plus an additional cysteine residue at the amino-terminus was coupled to keyhole limpet hemocyanin and used as the antigen for antiserum production. The ability of the antiserum to recognize mGHBP was demonstrated by incubating mouse serum with 125I-iodomouse GH (mGH) in the presence of increasing concentrations of antiserum and subsequent immunoprecipitation. The antiserum precipitated mGHBP in a dose-dependent manner. The uncoupled synthetic peptide was used as the standard and radioligand in the RIA. Serial dilutions of sera from non-pregnant or 17-days-pregnant mice yielded displacement curves parallel to the synthetic peptide, with serum from 17-days-pregnant mice being 32 times more effective than serum from non-pregnant mice for a given dilution. The relative concentration of mGHBP in maternal serum on days 5, 11, and 15 of pregnancy was 1, 17, and 39, respectively. PMID- 1733708 TI - Expression of thyroid hormone receptor beta 2 in rat hypothalamus. AB - A polymerase chain reaction based assay was used to evaluate expression of thyroid hormone receptor beta 2 mRNA in rat hypothalamus. Expression was detected in the arcuate, ventromedial and paraventricular nuclei, as well as the median eminence. Trace expression was found in the dorsomedial nucleus, but no expression of thyroid hormone receptor beta 2 was detected in the lateral hypothalamus or the preoptic region. The results indicate that, contrary to previous belief, expression of thyroid hormone receptor beta 2 is not confined to the anterior pituitary. PMID- 1733709 TI - A failed assay opened a new door in growth hormone research. PMID- 1733710 TI - Steroidogenesis-inducing protein promotes deoxyribonucleic acid synthesis in Leydig cells from immature rats. AB - A protein [steroidogenesis-inducing protein (SIP)] has been isolated from human ovarian follicular fluid and shown previously to stimulate steroidogenesis in Leydig cells, adrenal cells, and early luteal cells. Since proteins and peptides known to regulate steroidogenesis, such as gonadotropins and growth factors, also influence the growth of gonadal cells, the present study was designed to assess the effects of SIP on the synthesis of DNA by Leydig cells in vitro. Leydig cells were isolated from 10- and 20-day-old rats and cultured in serum-free medium for 48 h. The cells were then treated with the test materials for 18 h. Incorporation of [3H]thymidine into DNA was measured during the final 4 h of the culture. SIP significantly stimulated DNA synthesis in Leydig cells in a dose- and time dependent manner, and the response to SIP was higher than that obtained with maximal concentrations of LH/hCG. The stimulatory effects of SIP were significantly enhanced when the cell cultures were preincubated in the presence of low levels of ovine LH (2 ng/ml). Cultures treated with SIP, followed by incubation with [3H]thymidine, contained 22 times as many labeled cells as control cultures, as assessed by autoradiography. The cells that were labeled were identified morphologically as Leydig cells. Insulin/insulin-like growth factor-I and/or transforming growth factor-alpha alone stimulated DNA synthesis and enhanced the effects of SIP on DNA synthesis. Dramatic changes in the morphology of cultured Leydig cells treated with SIP were observed; cells became flattened and developed extended projections which connected adjacent cells. LH/hCG, insulin, and transforming growth factor-alpha did not induce effects comparable to those of SIP on the morphology of Leydig cells. The effects of SIP on the synthesis of DNA and the morphology of Leydig cells were blocked in the presence of cycloheximide. It is concluded that SIP not only stimulates steroid production in Leydig cells, as shown previously, but also stimulates DNA synthesis and induces morphological changes in these cells. The latter properties of SIP combined with the magnitude of the responses elicited identify SIP as a unique gonadal protein. PMID- 1733711 TI - The regulation of p33 gene expression by insulin and calcium ionophores. AB - We have previously shown that insulin induces p33 transcription and mRNA levels in serum-deprived rat H4 hepatoma cells. In the current study, the effects of the calcium ionophores A23187 and ionomycin on the regulation of p33 gene expression were examined. When H4 cells were incubated with A23187 or ionomycin (1 microM) for 90-300 min, 700-900% and 400-600% increases in p33 mRNA levels were observed. The effects of ionophore and insulin together on p33 mRNA levels were not additive. Insulin-induced increases in p33 mRNA levels were diminished at low concentrations of extracellular calcium, but were unchanged by the calcium channel blocker verapamil. The chelation of intracellular calcium using 20 and 60 microM quin2-AM resulted in 50% and 90% reductions in insulin-induced p33 mRNA levels. When transcription assays were performed, A23187 treatment for 15-180 min increased p33 transcription 300-400%. The lesser effect of A23187 on transcription compared to that on mRNA levels was also true for insulin treatment. Similar results were obtained using ionomycin. Insulin- and A23187 induced p33 transcription was reduced by quin2-AM to below basal levels. These studies show that calcium ionophores stimulate p33 gene expression and suggest that changes in intracellular calcium can alter insulin's induction of this gene. PMID- 1733712 TI - Tissue-specific regulation of fatty acid synthesis by thyroid hormone. AB - It is generally agreed that thyroid hormone stimulates the hepatic synthesis of long chain fatty acids in the rat. However, there are conflicting data about its effects in white adipose tissue, while in brown adipose tissue, lipogenic rates are highest in hypothyroid animals. We have systematically examined the effect of thyroid state on lipogenesis in different rat tissues. Fatty acid synthesis was assessed in vivo, using the incorporation of tritiated water. Hepatic lipogenesis was induced 16-fold between hypothyroid (4.1 +/- 0.6 microns H incorporated/g.h) and hyperthyroid rats (66.5 +/- 13.2 microns H/g.h). Kidney and heart were much less lipogenically active, but also responded positively to thyroid hormone. Both hyper- and hypothyroidism diminished fatty acid synthesis in retroperitoneal fat and had similar, although not significant, effects in epididymal fat. However, epididymal adipocytes, taken from hyperthyroid rats and cultured in vitro, were 3 times more lipogenically active than cells from either hypo- or euthyroid animals. Lipogenesis in sc fat from hyperthyroid rats was enhanced when calculated per g tissue, but was not different when expressed per whole tissue. In brown adipose tissue, lipogenesis was inversely related to thyroid hormone status. Fatty acid synthesis in brain, lung, skin, and bone and muscle did not respond to changes in thyroid state. TLC confirmed that greater than 90% of the incorporated tritium was in fatty acids. Thus, in hypothyroid animals, lipogenesis primarily occurs in skin, bone, muscle, and other nonresponsive organs, whereas in hyperthyroid rats, the liver alone constitutes almost half of all fatty acid synthesis. The fatty acid synthetic pathway provides an excellent model for examining the tissue-specific regulation of gene expression by thyroid hormone. PMID- 1733713 TI - Effects of hypothyroidism on hypothalamic release of thyrotropin-releasing hormone in rats. AB - The aim of this study was to investigate whether the severity and duration of primary hypothyroidism influence hypothalamic TRH release. Hypothyroidism was induced in male Wistar rats by treatment with different thyrostatic drugs or by thyroidectomy. Serum TSH in rats treated for up to 3 weeks with methimazole (MMI; 0.05% in drinking water) increased 20-fold, but TRH release into hypophyseal portal blood (HPB) did not change. Treatment with propylthiouracil (PTU; 0.1% in drinking water), which inhibits thyroidal T4 production and peripheral conversion of T4 to T3, resulted in a more rapid reduction in serum T3 levels and increase in serum TSH than those in rats treated with 0.1% MMI. Although these differences were no longer observed after 3 weeks of treatment, TRH release into HPB of rats treated with PTU was 34-49% higher than that in MMI-treated rats. Combined treatment with MMI (0.05-0.1% in drinking water) and iopanoic acid (IOP; 4 mg/100 g BW.day, ip), an inhibitor of both peripheral and central T4 to T3 conversion, also tended to produce a more rapid decrease in serum T3 and increase in serum TSH. After 3 weeks of treatment, serum T4, T3, and TSH were not different in the two groups, but TRH release into HPB was 48-65% increased by MMI plus IOP vs. MMI alone. Three to 10 weeks after thyroidectomy, TRH release into HPB was 58-72% higher than that in untreated controls. In vitro incubation of hypothalami isolated from rats treated for 3 weeks with MMI, MMI plus IOP, or PTU, as described above, showed that basal and 56 mM K(+)-induced TRH release were not influenced by the different drugs. Also, the total hypothalamic TRH content was not changed by any of these treatments. However, in rats treated for 1 or 2 weeks with MMI or PTU, the TRH content of the median eminence was decreased by 17-25%. These findings indicate that, depending on severity and duration, experimental hypothyroidism may cause a significant increase in hypothalamic TRH release in rats. The magnitude of these changes compared with the much larger increases in serum TSH suggests that the feedback of thyroid hormone on TSH secretion is mainly exerted at the pituitary level. PMID- 1733714 TI - Characterization of the insulinotropic potency of polyunsaturated fatty acids. AB - In this study we have assessed the individual abilities of the essential fatty acids, linoleic and linolenic acids, to release insulin and compared their insulinotropic potencies with those of the more established nutrient insulin secretagogues, glucose and arginine. In each experiment, a total of six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate buffer, pH 7.4, containing 2% bovine albumin and 5.5 mM glucose (basal) with a continuous supply of 95% O2-5% CO2 at 37 C for 1 h. After collecting basal samples, the effects of 27.7 mM glucose, 20 mM arginine, 10 mM linoleic acid (18:2, omega 6), and 5 mM linolenic acid (18:3, omega 3) were tested using a sandwich protocol that entails 20-min alternating periods of stimulation with a secretagogue and a washout with basal perifusion. These nutrient concentrations were selected from initial experiments performed to characterize their dose-response effects on insulin secretion. Effluent samples were collected throughout each experiment for measurement of insulin by RIA. In one series of experiments, islets were challenged three times with 27.7 mM glucose, 10 mM linoleic acid, and 5 mM linolenic acid. In another set of experiments, islets were perifused with 20 mM arginine, 27.7 mM glucose, and 10 mM linoleic acid. All of these nutrients stimulated insulin release in a dose dependent manner. In comparing the insulinotropic potencies of these secretagogues, we assessed insulin secretion as the integrated areas under the curve during 20 min of perifusion with a given nutrient. Thus, the mean integrated area under the curve per 20 min above basal in the presence of 27.7 mM glucose was 6,516 +/- 1,435 pg, which was not significantly different from the value of 4,772 +/- 866 pg obtained during arginine perifusion. However, the area under the curve during 20 min above basal obtained in the presence of linoleate and linolenic acid (8,712 +/- 1,949 and 10,506 +/- 1,490 pg, respectively) were significantly different (P less than 0.05) from those calculated during arginine and glucose perifusions. There was no statistically significant difference between the effects of these two fatty acids at the concentrations tested. In conclusion, our data suggest that linoleic acid and linolenic acid may be, at least in this murine islet preparation, as effective in stimulating insulin release as glucose and arginine, hitherto used to assess the abilities of nutrients to stimulate insulin secretion. However, it remains to be seen whether the efficacy of these polyunsaturated fatty acids in insulin release by murine islets will be obtained in experiments performed on human islets. PMID- 1733715 TI - Luteinizing hormone differentially regulates the secretion of testicular oxytocin and testosterone by purified adult rat Leydig cells in vitro. AB - The aims of the present study were to determine whether Leydig cells in vitro synthesize oxytocin, and whether LH modulates the secretion of oxytocin by Leydig cells. Highly purified adult Leydig cells were prepared from adult rats and cultured for 3 days in the presence or absence of 0.1 ng/ml ovine LH, and media were changed daily. The total amount of oxytocin present in the culture was estimated by RIA of cell extracts before culture (day 0) and at the end of day 3 of culture and in media on days 1-3. The content of immunoreactive oxytocin in cell extracts on day 0 (3.4 +/- 1.2 pg/10(6) cells) was significantly lower than the total amount that had been released into the medium and was present in the cell extracts at the end of day 3 (+LH, 27.8 +/- 3.3; -LH, 16.5 +/- 2.7 pg/10(6) cells), suggesting that Leydig cells are able to synthesize and secrete oxytocin. This hypothesis was supported by the observation that oxytocin release into the medium was significantly reduced during a 3-h treatment of Leydig cells with the protein synthesis inhibitor cycloheximide (5 micrograms/ml for 3 h). The role of LH in regulating testosterone production by Leydig cells is well defined, but whether LH also regulates oxytocin is unknown. Therefore, the effects of LH on oxytocin and testosterone production by Leydig cells were compared. The production of both hormones was stimulated by increasing doses of LH (0.001-100 ng/ml), but no further rise in oxytocin release could be elicited with amounts of LH greater than 0.1 ng/ml. Testosterone production, however, continued to increase with doses of LH up to 100 ng/ml. Furthermore, the two hormones differed in the rate of their responses to both 3- and 12-h exposures to LH; testosterone secretion increased more rapidly than that of oxytocin. These data provide direct evidence that adult Leydig cells produce immunoreactive oxytocin, and that their production of this peptide is regulated by LH. PMID- 1733716 TI - Prostatic involution in rats induced by a novel 5 alpha-reductase inhibitor, SK&F 105657: role for testosterone in the androgenic response. AB - Within the prostate, androgen stimulates glandular cell secretion and proliferation while inhibiting glandular cell death. Due to its predominant nuclear localization, higher affinity for the androgen receptor, and more than 10 fold higher intracellular concentration than testosterone, dihydrotestosterone (DHT), not testosterone, appears to be the active intracellular androgen within the prostate of intact male hosts. The issue has remained unanswered, however, whether testosterone itself, without irreversible conversion to DHT by the 5 alpha-reductase enzyme, is capable of androgenic effects in the prostate. To address this issue, a novel dead end (i.e. product) inhibitor of the 5 alpha reductase enzyme, SK&F 105657, was administered to intact or castrated male rats treated with either exogeneous testosterone or DHT. When administered twice a day orally at 25 mg/kg.dose, SK&F 105657 reduced the prostatic DHT content of either intact or castrated rats maintained with exogeneous testosterone to the same low level as that produced by surgical castration. Unlike castration, however, such SK&F 105657 treatment increased the prostatic testosterone content by more than 5 fold. The decrease in prostatic DHT coupled with a raise in testosterone are specifically due to the in vivo inhibition of the 5 alpha-reductase activity, since they were not observed in castrated rats maintained with exogeneous DHT. Treatment of intact or castrated male rats with exogeneous testosterone and oral SK&F 105657 (25 mg/kg, twice daily) resulted in a substantial inhibition of prostatic secretion, an inhibition of prostatic glandular cell proliferation, and an increase in prostatic glandular cell death. The magnitude of the changes, however, was not as great as that observed after surgical castration. The results are, however, specific for 5 alpha-reductase inhibition, since they were not observed in castrated rats given exogeneous DHT. These results demonstrate that if the prostatic testosterone content is elevated to sufficient levels, androgenic effects are induced without a requirement for an elevation in prostatic DHT content. Thus, the conversion of testosterone to DHT appears to function as a means of amplifying androgenic stimulation in the prostate. PMID- 1733717 TI - Dose-dependent effects of human prolactin on the immature hypophysectomized rat testis. AB - We have studied dose-dependent effects of highly purified human PRL (39 IU/mg) on the testis of immature (22-day-old) hypophysectomized rats daily supplemented for 7 days with 2, 10, or 30 micrograms hormone. Dose-dependent stimulation was observed for all parameters: testis weight (1.6- and 2-fold above control for 10 and 30 micrograms PRL), basal and hCG-stimulated testosterone (14- and 21-fold), intratesticular testosterone (7- and 21-fold) and estradiol (1.2- and 1.5-fold), LH receptor concentration (1.8- and 2.5-fold), in vitro pregnenolone production by cholesterol side-chain cleavage enzyme (3-, 5- and 7-fold), and aromatase activity (2.1- and 2.4-fold). The number of Leydig cells exhibiting immunoreactivity toward anti-P450scc, anti-P450(17 alpha), and anti-3 beta hydroxysteroid dehydrogenase antibodies also underwent a dose-dependent increase (under conditions revealing many immunopositive cells in hypox control animals). The respective increases were 8- to 14-fold for anti-P450scc and P450(17 alpha) and 1.5- to 2-fold for anti-3 beta-hydroxysteroid dehydrogenase. The number of germ cells and the percentage of tubular sections containing late pachytene spermatocytes as most advanced stages of spermatogenesis were subject to similar dose-dependent effects. These results suggest that during puberty PRL stimulates testicular function by promoting multiplication and differentiation of Leydig cells (acting at various steps of steroidogenesis and on tissue responsiveness to LH) and germ cells. PMID- 1733718 TI - Melatonin inhibits gonadotropin-releasing hormone-induced elevation of intracellular Ca2+ in neonatal rat pituitary cells. AB - GnRH stimulates LH release by increasing intracellular Ca2+ ([Ca2+]i). Melatonin is known to inhibit GnRH-stimulated LH release from neonatal rat pituitary cells. In the present report, the issue of whether melatonin acts through [Ca2+]i was addressed. [Ca2+]i was studied in cells in suspension, using Fluo-3 as a fluorescent indicator. In neonatal rat pituitary cells, melatonin inhibited the GnRH-induced [Ca2+]i increase in a dose-dependent manner; the GnRH-induced increase in [Ca2+]i was inhibited 40% by 100 nM melatonin. The relative potencies of several indoles as inhibitors of the GnRH stimulation of [Ca2+]i in neonatal pituitary cells (2-iodo-melatonin greater than melatonin greater than 6 hydroxymelatonin) correlate with their known potencies to inhibit LH release and with their binding affinity to high affinity melatonin receptors, which indicates that these receptors probably mediate the effects of melatonin. Further support for this interpretation comes from the observation that melatonin does not inhibit the GnRH effect on [Ca2+]i in cells obtained from adolescent rat pituitary glands, which lack melatonin receptors and are insensitive to melatonin as an inhibitor of GnRH-stimulated LH release. The possible involvement of an inhibitory G-protein was also investigated by studying the effects of pertussis toxin. Pretreatment with pertussis toxin antagonized the effects of melatonin on [Ca2+]i and LH release. This indicates that melatonin may inhibit the GnRH induced increase in [Ca2+]i through a mechanism involving a pertussis toxin sensitive G-protein. To examine the role of extracellular Ca2+ in this effect, the effects of melatonin were examined in a low Ca2+ medium. Under these conditions, the effect of melatonin was markedly reduced, which indicates that melatonin may act by inhibiting Ca2+ influx. These observations indicate that melatonin inhibits GnRH stimulation of [Ca2+]i in neonatal rat gonadotrophs, and this probably explains the inhibitory action of melatonin on GnRH stimulation of LH release. PMID- 1733719 TI - The hormonal regulation of platelet-activating factor-acetylhydrolase in the rat. AB - Platelet-activating factor-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF, is decreased in the plasma of both rabbits and humans during the latter stages of pregnancy. The activity of the enzyme was decreased in rats by the administration of 1,3,5(10)-estratrien-17 alpha-ethynyl-3,17 beta-diol (17 alpha ethynylestradiol) and increased by dexamethasone treatment. In the present study, we have further defined the hormonal regulation of PAF-AH levels in plasma of adult and juvenile rats. Estrone (E1), 17 beta-estradiol (E2), estriol (E3), and various progestins [4-pregnen-6 alpha-methyl-17 alpha-ol-3,20-dione (medroxyprogesterone), 4-estren-17 alpha-ethynyl-17 beta-ol-3-one (norethindrone), and 5(10)-estren-17 alpha-ethynyl-17 beta-ol-3-one (norethynodrel)] were administered to adult rats, and the plasma PAF-AH activities were assayed. E1, E2, and E3 administration to adult female rats lowered the plasma PAF-AH activity, E3 being the most effective. After administration of these estrogens the activity returned to the preinjection level within 4 days. The administration of medroxyprogesterone resulted in a 2-fold increase in plasma PAF-AH activity in adult female rats, and the activity remained elevated for up to 30 days. When adult male rats were treated with similar doses only a 20% increase was observed and the PAF-AH activity returned to control values by day 10. In contrast, norethindrone and norethynodrel administration resulted in a reduction of the enzyme activity in adult female rats. The plasma PAF-AH activity in juvenile male and female rats (3 weeks of age, 45-60 g body wt) was two times higher than that in adult rats of both sexes and spontaneously decreased up to the time of puberty. When juvenile male or female rats were injected with either 17 alpha-ethynylestradiol or medroxyprogesterone, a minimal change in PAF-AH activity was observed. In contrast, when dexamethasone was administered to juvenile male and female rats the plasma PAF-AH activity increased in a manner similar to adult animals. It is suggested that estrogens cause a decrease and medroxyprogesterone an increase in plasma PAF-AH activity. It is suggested that the different responsiveness to medroxyprogesterone between adult female and male rats and juvenile animals may depend on the concentration of the hormone receptor in the tissue responsible for the synthesis of PAF-AH. The decrease in PAF-AH activity after the administration of norethindrone and norethynodrel may be due to the known estrogenic activity of these steroids. PMID- 1733720 TI - pH homeostasis in pituitary GH4C1 cells: basal intracellular pH is regulated by cytosolic free Ca2+ concentration. AB - In GH4C1 cells, membrane depolarization induces a rapid and sustained increase in the cytosolic free calcium concentration ([Ca2+]i). In the present study we have investigated the role of [Ca2+]i in the regulation of basal intracellular pH (pHi). Depolarizing GH4C1 cells in buffer containing 0.4 mM extracellular Ca2+ decreased basal pHi from 7.02 +/- 0.04 to 6.85 +/- 0.03 (P less than 0.05). If the depolarization-induced influx of Ca2+ was inhibited by chelating extracellular Ca2+ or blocking influx through voltage-operated Ca2+ channels with nimodipine, no acidification was observed. Addition of TRH induced a rapid activation of Na+/H+ exchange in acidified cells, increasing pHi by 0.14 +/- 0.03 U. The action of TRH was blunted if extracellular Ca2+ was chelated; however, if influx of Ca2+ via voltage-operated channels was blocked by nimodipine, TRH still increased pHi. To deplete ATP, we incubated cells with 2-deoxy-D-glucose for 15 20 min and observed a decrease in basal pHi to 6.75 +/- 0.03 (P less than 0.05). No additional acidification was obtained when 2-deoxy-D-glucose-treated cells were depolarized, and no TRH-induced activation of Na+/H+ exchange was observed. Addition of ionomycin or 12-O-tetradecanoyl-phorbol-13-acetate separately to acidified cells had only modest effects on pHi; however, addition of 12-O tetradecanoyl-phorbol-13-acetate and ionomycin together increased pHi markedly. We conclude that in GH4C1 cells, increasing [Ca2+]i reduces basal pHi through a mechanism dependent on influx of extracellular Ca2+ and independent of Na+/H+ exchange. In addition, elevation of [Ca2+]i and activation of protein kinase C act synergistically to enhance Na+/H+ exchange and increase pHi in acidified cells. Finally, normal cellular ATP is necessary for the activation of Na+/H+ exchange. PMID- 1733721 TI - Treatment of insulin-resistant mice with the oral antidiabetic agent pioglitazone: evaluation of liver GLUT2 and phosphoenolpyruvate carboxykinase expression. AB - Obese KKAy insulin-resistant mice represent a model for the human syndrome of noninsulin-dependent diabetes mellitus. As such, the animals are hyperglycemic and hyperinsulinenic. Treatment of KKAy mice with pioglitazone, a new antihyperglycemic agent, lowered elevated blood glucose and insulin levels to near normal. Since hepatic glucose overproduction is a key abnormality in noninsulin-dependent diabetes mellitus, the aim of the present study was to define the specific effects of pioglitazone on hepatic glucose metabolism and release. To do so, we evaluated the expression of the major liver glucose transporter, GLUT2, and examined the activity and expression of the major rate limiting enzyme for gluconeogenesis, phosphoenolpyruvate carboxykinase. Our results showed that GLUT2 mRNA abundance was unchanged in diabetic KKAy mice compared to nondiabetic animals, and that no changes were elicited by pioglitazone treatment. Such unaltered GLUT2 levels were consistent with a role for liver GLUT2 in bidirectional transport of glucose during physiological states of uptake or release. In contrast, phosphoenolpyruvate carboxykinase activity and mRNA abundance were concordantly elevated 2-fold in diabetic animals and were returned to normal levels after treatment with pioglitazone. Given that pioglitazone therapy led to decreased hepatic gluconeogenesis while insulin levels were concomitantly lowered, it appeared that pioglitazone acted to restore sensitivity to insulin's normal inhibitory actions. PMID- 1733722 TI - Concentrations of parathyroid hormone-related protein in rat milk change with duration of lactation and interval from previous suckling, but not with milk calcium. AB - PTH-related protein (PTHrP) is found in high concentrations in the milk of various mammals. However, little is known about the regulation of PTHrP production or the physiological role(s) of PTHrP in the mammary glands. To address these questions, we examined in lactating rats 1) the longitudinal changes in PTHrP concentrations in milk and PTHrP mRNA levels in the mammary glands throughout lactation, 2) the effects of the nonsuckling interval on milk PTHrP concentration, and 3) the correlation between PTHrP and calcium concentrations in milk. PTHrP concentrations in milk, measured by RIA and in vitro bioassay, increased with the duration of lactation. The maximal concentrations of PTHrP (observed between days 19-21 of lactation in rats milked serially) were 4.8- to 8.0-fold higher than the concentrations on day 7. PTHrP mRNA levels in the mammary glands also increased during the late stages of lactation. The longitudinal changes in calcium concentrations in milk were small and did not parallel the changes in PTHrP. When pups were removed from the mother for 4-24 h, milk PTHrP decreased while calcium increased in a time-dependent manner. As a whole, calcium concentrations in milk did not correlate with PTHrP throughout lactation. These data suggest that the production and secretion of PTHrP into milk are regulated independently of the other major milk proteins by a factor(s) that changes with progression of lactation and in relation to suckling status. PMID- 1733723 TI - Altered glucose regulation of insulin biosynthesis in insulinoma cells: mouse beta TC3 cells secrete insulin-related peptides predominantly via a constitutive pathway. AB - The effects of glucose on insulin gene expression and proinsulin biosynthesis, processing, and secretion were studied in mouse beta TC3 cells, an established insulinoma cell line derived from transgenic mice carrying a hybrid insulin promotor-simian virus-40 tumor antigen. The level of insulin mRNA was maintained at high levels by culture in 11 mM glucose, but essentially disappeared after 48 h of culture without glucose. The rate of insulin biosynthesis in beta TC3 cells was also dependent on glucose concentration over periods of 24 or 48 h (but not during 3 h) of stimulation. Insulin biosynthesis decreased about 50% after 24 h and about 85% after 48 h of incubation without glucose. When beta TC3 cells were incubated without glucose for 48 h, the rate of conversion of proinsulin to insulin was decreased compared to that at 11 mM glucose. Insulin secretion was sustained by medium glucose and also exhibited a much lower threshold for maximal stimulation; 2-deoxyglucose uptake decreased about 50% after 48 h of incubation without glucose. Studies on the secretion of newly synthesized proinsulin/insulin revealed that up to 80% of the total cellular pool of labeled proinsulin was released during a 60-min chase compared to only 10% of labeled insulin. The release of immunoreactive insulin (IRI) during the chase period was stimulated by forskolin and phorbol-12-myristate-13-acetate 1.6- and 10-fold, respectively. However, the release of newly synthesized proinsulin was insensitive to these secretagogues. It is concluded that 1) as in normal islets, glucose influences the steady state levels of proinsulin mRNA in beta TC3 cells; 2) the rate of proinsulin biosynthesis reflects only the level of insulin mRNA; translational control is absent; 3) cellular conversion of proinsulin to insulin is up regulated by glucose as in normal rat islets; 4) newly synthesized proinsulin is released predominantly via a constitutive, rather than a regulated pathway, in contrast to normal beta-cells. PMID- 1733724 TI - Thyroid hormones and 5'-deiodinase activity in neonatal undernourished rats. AB - Undernutrition was induced in rats submitted to food restriction from the fetal stage, and malnutrition was continued after birth until 70 days of life. Body weight was decreased to less than 50%. Plasma T4 and T3 and pituitary TSH content were determined between 8-70 days of life. In control rats, plasma T4 and T3 reached a maximum at 14 and 35 days of life, respectively, and TSH pituitary content at 45 days of life. In undernourished rats, after 8 days of life, plasma T4 and T3 and pituitary TSH content were decreased to about 50% or less, and the pattern of sequential changes observed in control rats was absent or modified. T4 and T3 concentrations were measured in heart, liver, and brain in the fetus (22 days old) and 8, 14, and 23 days after birth, as well as liver and brain 5' deiodinases (5'D). Hepatic 5'D type I was always decreased in undernourished rats from 8-70 days after birth. Liver and heart T4 and T3 concentrations were decreased in 14-day-old undernourished rats as well as brain T3. Brain 5'D type II was decreased at 8 and 14 days, and total brain 5'D activities at 8 days. These changes occurred during the critical period for brain development (7th to 20th day) during which most processes of myelination take place and T3 brain normal levels are required. PMID- 1733725 TI - Purification and characterization of high molecular weight forms of inhibin from bovine follicular fluid. AB - High molecular mass forms [95 kilodaltons (kDa)] of bovine inhibin-A as well as the known forms of intermediate (55 kDa) and low (32 kDa) mass were purified from bovine follicular fluid by ion exchange chromatography on DEAE-Sepharose, immunoaffinity chromatography using a monoclonal antibody directed against bovine 32-kDa inhibin-A, gel permeation HPLC on TSK-gel, and reverse phase HPLC. The 95 kDa inhibin-A had similar suppressive activity on FSH secretion from cultured rat anterior pituitary cells as the 55- and 32-kDa inhibins. There is, however, a possibility that the inhibin activity detected with larger forms may be due to that of the 32-kDa form that results from proteolytic processing during incubation with rat pituitary cells. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis using monoclonal antibodies specific for 32-kDa inhibin alpha- or beta A-subunits revealed that the 95-kDa inhibin preparation contained two forms of inhibin (105 and 95 kDa), which were composed of either a 50- or a 40-kDa alpha-subunit linked by a disulfide bond(s) to a 55-kDa beta A-subunit. Amino-terminal sequence analysis showed that the 50-kDa alpha-subunit and the 55-kDa beta A-subunit were generated by removal of a signal peptide from each corresponding primary translation product [the first NH2-terminal 17 residues of the inhibin alpha-subunit (residues 1-360) and the first 20 residues of the inhibin beta A-subunit (residues 1-425)] and suggested that the 40-kDa alpha-subunit was formed by proteolytic processing of the 50-kDa alpha-subunit. On the basis of our findings, we propose that in bovine follicular fluid, the larger 105-kDa form of inhibin is processed successively to form the lowest molecular mass form, 32 kDa inhibin, through the smaller 95- and 55-kDa forms. PMID- 1733726 TI - Glucocorticoid regulation of plasminogen activator inhibitor-1 messenger ribonucleic acid and protein in normal and malignant rat osteoblasts. AB - Glucocorticoids exert potent inhibitory effects on bone formation. We have previously shown that glucocorticoids suppress plasminogen activator (PA) activity in normal and malignant rat osteoblasts. To clarify the mechanism of this suppression, we investigated the effects of dexamethasone on PA inhibitor-1 (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) expression and also on PAI-1 protein and PA activity in both normal rat calvarial osteoblasts and a clonal osteogenic sarcoma cell line, UMR 106-01. Dexamethasone increased PAI-1 mRNA and protein in both cell types. The increase in PAI-1 protein and the decrease in PA activity were obtained over the same concentration range, with a half-maximally effective concentration of dexamethasone of about 10(-9) M. The increase in PAI-1 mRNA caused by dexamethasone was retained with cycloheximide treatment, but abolished with actinomycin-D. Dexamethasone had no effect on tPA or uPA mRNA in either cell type. The glucocorticoid antagonist RU 486 prevented the effects of dexamethasone on PA activity and PAI-1 protein. Dihydrotestosterone, progesterone, and 17 beta-estradiol did not influence PA activity or PAI-1 formation. Although tPA and uPA protein could not be measured, these results suggest that glucocorticoids suppress PA activity predominantly by increasing PAI-1 synthesis in rat osteoblasts. Suppression of PA activity through actions on PAI-1 formation by glucocorticoids could contribute to the mechanisms by which glucocorticoids inhibit bone formation. PMID- 1733727 TI - Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice. AB - The relative contributions of ovarian and extra-ovarian factors to the altered ovarian steroidal profiles of middle-aged mice were assessed by reciprocal, heterochronic ovarian grafting. Ovaries from cycling, young (2 months), and middle-aged (12 months) mice were exchanged by grafting under the renal capsules. Blood samples were obtained daily at midday throughout the estrous cycle for measurement of estradiol (E2) and 3-4 h after lights-out on proestrus to measure the preovulatory elevation of progesterone (P4). Middle-aged intact mice had lower mean concentrations of E2 during the cycle, no detectable midday preovulatory elevation of E2, and an attenuated preovulatory increase of P4 compared to young mice. Ovarian grafts from young donors failed to increase mean E2 levels of middle-aged mice, but did restore the preovulatory elevation of E2 and preovulatory P4 to levels of young controls. Reciprocal grafting confirmed these findings: ovaries from middle-aged donors in young hosts produced mean E2 levels equivalent to those of young mice but were unable to support a preovulatory increase of E2 or a preovulatory P4 level equivalent to that of young controls. These results reveal differential contributions of ovarian and extra-ovarian factors to age changes in E2 and P4. They indicate that ovarian aging plays an important role in attenuating the preovulatory increase of E2 and P4, but extra-ovarian, presumably neuroendocrine, age changes underlie the mean reduction of E2 levels across the estrous cycle. PMID- 1733728 TI - Prolactin variants in ram adenohypophyses vary with season. AB - Secretion of PRL in sheep is affected by photoperiod being highest during the spring and summer, lowest in fall and winter. The objectives of this study were to determine if 1) the production of variant forms of PRL, and 2) immuno- and bioactivities of PRL (iPRL and bPRL) differ during times of the year selected to represent periods of low, transitional and high PRL secretion. Twelve mature rams were maintained on pasture and killed in October, December, and April (n = 4/month). Individual pituitary glands were dispersed, cells obtained, and fixed for immunocytochemical flow cytometry, extracted with 0.01 N NaHCO3 or cultured in serum-free, defined media. The Mr of PRL extracted from cells immediately following dispersion ranged from 14-140K, with significantly more bands greater than 40K being detected from rams sacrificed in December than from those killed in October and April (P less than 0.01). No bands of PRL greater than 25K were observed when samples were reduced with beta-mercaptoethanol prior to electrophoresis, indicating that the high Mr forms were disulfide-linked aggregates. Culture media from October and April contained variants of PRL that ranged from 22-40K but those greater than 25K were generally not observed from cells harvested during December. Extracts of cells after 24 h in culture contained fewer high Mr species during December than had been present in initial extracts from that month. In contrast, during April more high Mr intracellular forms were present after culture than had been detected prior to culture during that month. The percentage of lactotrophs averaged 50.0 +/- 2.5, 47.4 +/- 5.7, and 59.4 +/- 5.5 for October, December, and April, respectively. Initial lactotroph content (pg/lactotroph) of iPRL was higher (P = 0.06) in April (46.0 +/- 17.0) when compared to October and December (8.0 +/- 2.0 and 20.0 +/- 10.0, respectively). In contrast, the bPRL content of initial extracts was higher (P = 0.05) in December (267.0 +/- 68.0) than in October (101.0 +/- 35.0), but not than in April (190.0 +/- 70.0). Although iPRL and bPRL concentrations in culture media were similar for the 3 months, the intracellular iPRL (P less than 0.001) and bPRL (P less than 0.0001) content after culture was greatest during April. In summary, in addition to the well-documented seasonal changes in blood concentrations of PRL, different molecular forms of PRL were found within the pituitary at different times of the year and seasonal variations in iPRL and bPRL did not occur in parallel. PMID- 1733729 TI - Dehydration attenuates plasma prolactin response to suckling through a dopaminergic mechanism. AB - The tuberoinfundibular dopaminergic neurons projecting to the median eminence are well accepted as a major physiological regulator of adenohypophyseal PRL secretion. However, recent evidence has shown that dopamine (DA) in the neurointermediate lobe also has an inhibitory effect on PRL secretion by anterior pituitary. Since the neurointermediate is innervated by the tuberohypophyseal dopaminergic (THDA) neurons, which is known to be selectively activated by dehydration of the animal, the aim of this study was to investigate the physiological role of the THDA system in PRL release during lactation. On the day of the experiments, the litters were separated from the mothers for 4 h before initiation of the suckling stimulus. The suckling-induced PRL surge was detected on three consecutive days. On the first day the normal response was tested; then immediately after taking the last blood samples, drinking solutions were changed to the high salt (2.5% saline) containing bottles or were taken away. Suckling induced PRL response was significantly decreased after 24 h and almost completely blocked 48 h later in dehydrated mothers. This effect could be prevented by haloperidol (a DA receptor antagonist) pretreatment (0.1 mg/kg BW sc), and it was only transient because rehydration of the mothers reestablished basal as well as suckling-induced PRL response. In addition, the effect of an acute osmotic stimulus on the plasma PRL levels (injecting 0.5 ml 10% saline solution iv) was also tested. There was a marked and immediate decrease in PRL concentration within 15 min of injection. Domperidone, another DA receptor blocker (20 micrograms/rat iv) completely abolished the depletion of plasma PRL in response to 10% saline injection. These results support our assumption that the dopaminergic regulation of PRL secretion during lactation involves the THDA system. Furthermore, these data underline the importance of an interaction between regulation of PRL secretion and water and sodium homeostasis. PMID- 1733730 TI - Nerve growth factor enhances [3H]nicotine binding to a nicotinic cholinergic receptor on PC 12 cells. AB - Although nicotinic cholinergic agonists have functional effects on PC 12 cells, radioligand-binding sites have not been detected. We, therefore, studied PC 12 cells incubated in the presence of nerve growth factor (NGF) and determined that specific [3H]nicotine-binding sites were induced approximately 2.5-fold in the presence of NGF (50 or 100 ng/ml). Specific binding was maximal between the first (100 ng/ml NGF) and seventh (50 ng/ml NGF) days of treatment and was stable for 2 weeks with addition of NGF every 3 days. Using intact cells, average association and dissociation rates for [3H]nicotine were 0.00021 min-1 nM-1 (n = 2) and 0.048 min-1 (n = 2), respectively, at 4 C, yielding an average apparent Kd of 229 nM. At 22 C, stable equilibrium was not attained during association studies. A similar Kd value for broken cell preparations was obtained by kinetic analysis (i.e. an average association rate of 0.00042 min-1 nM-1 and dissociation rate of 0.087 min-1), yielding an average Kd value of 207 nM (n = 2) at 4 C. By saturation binding analysis of intact cells, an average Kd of 292 nM (n = 2) and a binding capacity (Bmax) of 15,118 molecules/cell were obtained. [3H]Nicotine binding was inhibited on an equimolar basis by L-(-)nicotine and N methylcarbamylcholine. D-(+) Nicotine was 7-fold less potent, whereas alpha bungarotoxin, mecamylamine, and atropine showed no significant inhibition. [3H]Nicotine binding was also inhibited quantitatively by mono-specific polyclonal antibodies raised against the predicted alpha 3-subunit sequence (amino acids 130-139) of the rat neuronal nicotinic cholinergic receptor. This study represents the first biochemical characterization of NGF-stimulated nicotine-binding sites on PC 12 cells and confirms previous evidence of the presence of functional nicotinic cholinergic receptors on these cells. PMID- 1733731 TI - Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability. AB - Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived cytokine that is also reportedly produced by granulosal cells and is localized in luteal cells. The present study employed serum-free culture of midcycle bovine luteal cells to investigate the effects of TNF-alpha, alone and with other cytokines, on luteal function. TNF-alpha (1-1000 ng/ml) produced a dose-dependent increase in prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha synthesis on all days of culture, but had no effect on basal progesterone (P4) production. TNF-alpha, in combination with other known stimulators of luteal PG synthesis, interleukin-1 beta (2.5 ng/ml) or interferon-gamma (IFN-gamma, 100 U/ml), had synergistic effects on PGF2 alpha production (greater than 50-fold above control, P less than 0.05) whereas interferon-alpha (1000 U/ml) significantly suppressed TNF-alpha stimulated PGF2 alpha production. By day 7 of culture, TNF-alpha inhibited LH stimulated P4 production (P less than 0.05). Luteal cell numbers were significantly reduced by IFN-gamma but not by TNF-alpha alone. However, the combination of TNF-alpha + IFN-gamma was extremely cytotoxic (only 20% of cells maintained as compared to control). Finally, TNF-alpha (100 ng/ml) enhanced the expression of Class I major histocompatibility complex antigens on cultured bovine luteal cells but did not alter IFN-gamma induction of Class II major histocompatibility complex antigens. In light of these findings, it appears that TNF-alpha, in conjunction with other cytokines, is a modulator of luteal cell function in vitro. The stimulation of PG synthesis, as well as cytotoxic effects of TNF-alpha, may suggest a role in luteolysis. PMID- 1733732 TI - The expression of 15-lipoxygenase gene and the presence of functional enzyme in cytoplasm and nuclei of pregnancy human myometria. AB - The expression of the 15-lipoxygenase (15-LO) gene in pregnancy human myometria, from messenger RNA (mRNA) to the product of the enzyme reaction, was investigated. In situ hybridization with antisense riboprobe synthesized from human reticulocyte 15-LO complementary DNA has revealed the presence of mRNA in myometrial smooth muscle as well as in myometrial blood vessels. Immunoblot analysis with a polyclonal antibody to recombinant human 15-LO enzyme showed a single 110-kilodalton immunoreactive protein in myometria. Light microscope immunocytochemistry using polyclonal antibodies has demonstrated the presence of immunoreactive 15-LO protein and 15-hydroxyeicosatetraenoic acid (15-HETE), the primary product of the 15-LO pathway. While myometrial blood vessels did not show any obvious change, myometrial smooth muscle showed lower 15-LO mRNA, 15-LO immunoreactive protein, and 15-HETE at term pregnancy and during labor. Immunogold electron microscopy showed the presence of immunoreactive 15-LO in rough endoplasmic reticulum and 15-HETE in myofilaments. Quite unexpectedly, both are also present in nuclear chromatin. In summary, the present study demonstrates for the first time the expression of 15-LO gene in pregnancy human myometria and the mRNA and catalytically active enzyme are lower at term pregnancy and during labor. Quite unexpectedly, catalytically active 15-LO is also present in nuclear chromatin. These findings suggest that 15-LO/15-HETE may have genomic as well as nongenomic actions, both of which may either initiate and/or facilitate the progression of labor in women. PMID- 1733733 TI - Immunocytochemical localization of progestin receptors in monkey hypothalamus: effect of estrogen and progestin. AB - The increase in PRL secretion which follows progesterone (P) administration to estradiol (E)-primed women and monkeys cannot be due to an action of P at the pituitary level because lactotropes do not contain progestin receptors (PR). To further the hypothesis that P increases PRL secretion by an action in the hypothalamus, PR-expressing neurons were studied in free-ranging and steroid manipulated monkeys using immunocytochemistry with a monoclonal antibody to human PR. Specific PR immunoreactivity is localized in the nucleus of individual hypothalamic neurons. Male and female adult and juvenile macaque hypothalami contain significant populations of PR-positive neurons throughout the anterior and medial basal hypothalamus. Ovariectomy decreases, but does not abolish, the number of neurons expressing PR. PR expression was not altered in the supraoptic nucleus (SON) by ovariectomy. Estrogen treatment for 28 days caused a significant increase in the number of PR-positive neurons in the medial preoptic area, the ventro-medial nucleus, the arcuate nucleus, and the median eminence, but not in the SON. P treatment added to the E treatment from day 14 to day 28 did not alter the number of PR-positive neurons in any area. These data suggest that PR may be constitutively expressed in the magnocellular neurons of the SON and in certain other cells throughout the hypothalamus. E induces PR in a large proportion of neurons in the medial basal hypothalamus and this action is not blocked by subsequent P treatment. The inability of P to down-regulate PR in the hypothalamus differs from the reproductive tract and pituitary. Indeed, this observation is consistent with the fact that PRL secretion remains elevated during chronic P administration. PMID- 1733734 TI - The stimulatory and inhibitory effects of dopamine on prolactin secretion involve different G-proteins. AB - The reverse hemolytic plaque assay (RHPA) was used in this study to further characterize the mechanism whereby low concentrations of dopamine (DA) stimulate PRL secretion in vitro. Female Sprague-Dawley rats were used as a source of anterior pituitary cells for the RHPA. Pituitary cells were infused into Cunningham chambers along with a suspension of protein-A-coated ovine red blood cells. Excess cells were rinsed from the chambers leaving a monolayer of cells attached to the glass. The cells were then incubated with solutions containing PRL antiserum (1:40) and various concentrations of DA. After 4 h, a solution containing guinea pig complement (1:60) was infused into the chambers. Thirty minutes later, the cells were fixed and plaques (zones of hemolysis) surrounding PRL-producing cells (lactotrophs) were measured and used as an index of the amount of PRL secreted. Control cells that received no DA had a mean plaque area of 8,000 microns 2 and two distinct subpopulations of plaque sizes. This biphasic population of cells consisted of a small and a large plaque producing population. The mean plaque area surrounding lactotrophs was significantly (P less than 0.05) decreased if 1 microM or 10 microM DA was present (4,500 microns 2 and 3,500 microns 2, respectively). These cells which received inhibitory concentrations of DA demonstrated a monophasic distribution of plaque-forming cells. On the other hand, mean plaque area was significantly (P less than 0.05) increased if 0.1 nM or 1 nM DA was presented to the cells (15,000 microns 2 and 14,500 microns 2, respectively). These cells receiving stimulatory doses of DA exhibited a multiphasic distribution of plaque-forming cells. The possibility that the two physiological opposing actions of DA on PRL secretion might be mediated by different GTP binding proteins was also examined using cholera toxin (CTX) and pertussis toxin (PTX). Anterior pituitary cells were pretreated with either CTX (50 micrograms/ml) or PTX (5 micrograms/ml) for 1 h before initiation of the RHPA. In the RHPA, cells received no DA, a stimulatory dose of DA (0.1 nM), or a inhibitory dose of DA (10 microM). The effects of toxin pretreatment on mean plaque area of DA-treated cells was determined. PTX pretreatment significantly attenuated the inhibitory effects of DA while having no effect on the stimulatory effects of DA on PRL secretion. CTX significantly (P less than 0.05) potentiated the stimulatory effects of DA on PRL secretion and had no effect on inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1733735 TI - Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain. AB - T4 is bound to transthyretin (TTR; 75%) and albumin (Alb; 25%) in rat serum and only to TTR in cerebrospinal fluid (CSF). In addition to the liver, TTR is synthesized in large amounts in the choroid plexus and then secreted into the CSF, suggesting that serum T4 could be transported to the CSF and brain via the choroid plexus. We determined whether serum T4 bound to TTR is transported into the choroid plexus and CSF. N-Bromoacetyl-L-[125I]T4, a derivative of T4 that binds covalently to TTR, was used as the affinity label for the T4-binding site on TTR. Rats were injected with [125I]T4, acetyl-[125I]T4 covalently bound to human TTR ([125I]T4Ac.human hTTR), or acetyl-[125I]T4 covalently bound to human Alb ([125I]T4Ac.hAlb). The quantities of [125I]T4Ac.hTTR and [125I]T4Ac.hAlb present in the choroid plexus, CSF, and brain 90 min later were barely detectable. In contrast, [125I]T4 injected as the unbound form accumulated in the choroid plexus and CSF to levels 6-11 times higher than with [125I]T4Ac.hTTR (P less than 0.005). We then used a synthetic flavonoid (EMD) that competitively inhibits binding of T4 to serum TTR and transiently increases serum free T4 to determine the role of choroid plexus TTR and CSF TTR in the transport of T4 from serum to brain. Rats were given 110 microCi [125I]T4 15 min after the injection of vehicle, a low (0.3 mumol/100 g BW) or high dose of EMD (2.0 mumol/100 g BW). Rats were killed 60 min later. In serum, the percentage of [125I]T4 bound to TTR decreased and free T4 increased similarly in the low and high dose EMD-treated rats. In contrast, the percentage of [125I]T4 bound to TTR in choroid plexus and, subsequently, CSF was significantly decreased in rats given the high dose of EMD, but was not affected by the low dose of EMD, suggesting that in high doses, EMD crossed from serum to choroid plexus and CSF and occupied TTR-binding sites for T4. There was a significant decrease (P less than 0.05) in the percentage of injected [125I]T4 in the high dose vs. the low dose EMD-treated rats in total choroid plexus (61%), 1 ml CSF (94%), and 1 g cerebral cortex (46%) and cerebellum (46%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1733736 TI - Calcium signalling in single growth hormone-releasing factor-responsive pituitary cells. AB - The release of pituitary GH appears to be critically dependent on alterations in the free intracellular Ca2+ concentration ([Ca2+]i). However, little is known about the nature of Ca2+ signalling within normal pituitary cells. We, therefore, examined [Ca2+]i patterns in individual cultured pituicytes of adult male rats under basal conditions and in response to GH regulatory agents, using the calcium sensitive dye fura-2 together with digital imaging microscopy. Perfusion of cultured anterior pituitary cells with GH-releasing factor (GHRF) resulted in a marked increase in [Ca2+]i in specific pituitary cells. These cells did not respond to other hypothalamic secretagogues (GnRH, TRH, or CRF), and there was no evidence of desensitization on repetitive administration of GHRF. Somatotrophs (n = 134) exhibited spontaneous oscillations of [Ca2+]i in the basal state, with considerable heterogeneity of oscillatory patterns among cells. After application of a near-maximal stimulatory dose of GHRF (1 nM), there was a striking 2.2-fold increase in the amplitude of [Ca2+]i oscillations and only a modest increase in their frequency. Forskolin (1 microM) augmented somatotroph [Ca2+]i in patterns similar to those of GHRF. Somatostatin (10 nM) abolished the [Ca2+]i response to GHRF (n = 26); this reflected a marked reduction in the amplitude of [Ca2+]i oscillations and a slight reduction in their frequency. Ca(2+)-free medium or the Ca2+ channel antagonist nimodipine (0.1-1 microM) suppressed the Ca2+ stimulatory effect of GHRF. Conversely, the Ca2+ channel agonist BAY K8644 (1 microM) strikingly augmented the GHRF-induced rise in [Ca2+]i, with a major stimulatory effect on the amplitude of [Ca2+]i oscillations and no observed effect on their frequency. In summary, GHRF and other hypothalamic secretagogues increase [Ca2+]i in pituitary cells in a highly specific manner, consistent with the known specificity of their effects on hormone release. Somatotrophs exhibit spontaneous rhythmic oscillation of [Ca2+]i in the basal state. Known regulators of GH release markedly alter the [Ca2+]i oscillatory pattern in characteristic manners, exerting predominant effects on the amplitude of [Ca2+]i pulses and lesser effects on their frequency. These striking effects of GH regulatory agents on pituitary Ca2+ signalling are consistent with the concept that modulation of [Ca2+]i is a critical mediator of somatotroph function. PMID- 1733737 TI - Isolation, characterization, and culture of cell subpopulations forming the pregnant rat corpus luteum. AB - The aim of this investigation was to isolate, characterize, and culture the small and large luteal cell subpopulations forming the corpus luteum of the pregnant rat. Since the large luteal cells are extremely fragile and do not survive standard cell dispersion, a method which allows the survival and the long-term culture in serum-free media of small and large cells was developed. The two luteal cell populations differed not only by their size but also by their morphology in culture. The small luteal cells (12-20 mu in diameter) are characterized by a large oval nucleus, contain few lipid droplets and have a stellate shape. In contrast, the large luteal cells have a smaller spherical nucleus, high lipid content, and do not flatten out completely in culture, most probably due to the abundance of lipid droplets. Both luteal cell types express 3 beta HSD and the cytochrome P450 enzymes involved in steroidogenesis. However, it is the lipid filled large luteal cells that secrete the most progesterone, androgen, and estradiol; express greater amounts of P450scc and P450AROM; and possess more PRL and LH receptors. Despite the greater expression of LH receptor in the large luteal cells, small and large luteal cells responded to LH with equal increase in steroidogenic output. In serum free culture, luteal cells produced progesterone for up to 20 days; however, an exogenous source of cholesterol was a prerequisite for maximal progesterone secretion. The pattern of progesterone secretion by cultures of small and large luteal cells differed remarkably from that of mixed cell population. When nonsteroidogenic corpus luteum cells were cocultured with the large luteal cells, a severalfold increase in progesterone secretion was observed. This stimulation occurred even when cells were cocultured in the absence of exogenous source of cholesterol. In summary, a successful method was developed to disperse, isolate, and independently culture the two luteal cell populations forming the rat corpus lutem. The results indicate that the marked difference in the steroidogenic capacity of these two cell populations is due, in large part, to the difference in their size rather than to their origin in the follicle. In addition, the results have revealed an important effect of the nonsteroidogenic cells forming the corpus luteum on luteal cell steroidogenesis. PMID- 1733738 TI - Characterization of monoclonal antibodies to the human thyrotropin receptor. AB - We have produced four monoclonal antibodies (mAbs), 34A, 49G, 11E7, and 12E3, which bind the human TSH receptor (hTSH-R) when expressed on a human thyroid cell line (GEJ), freshly dissociated human and murine thyroid cells, or Chinese hamster ovary cells stably transfected with the hTSH-R gene. These mAbs were obtained after immunization of DBA/1 mice with affinity-purified TSH-binding sites from GEJ cells. Biochemical studies, including sodium dodecyl sulfate polyacrylamide-gel electrophoresis, Western blot, and immunoprecipitation of solubilized GEJ cell membranes or human thyroid cells showed that most of the mAbs recognized two bands: one located at 46-48 kilodaltons and the other at 86 88 kilodaltons. Inhibition of [125I]hTSH binding to solubilized porcine membranes (TSH-receptor auto-antikorper assay) or Chinese hamster ovary cell membranes previously transfected with hTSH-R gene showed that mAb 34A recognizes the hTSH binding site of both receptors. In contrast, mAbs 49G, 11E7, and 12E3 recognize a structure located near the hTSH-binding site. Lastly, the ability of these mAbs to stimulate murine thyroid function was investigated by measuring cAMP production and iodide accumulation. The 34A mAb, which fully competes with [125I]TSH for binding to hTSH-R, was able to induce both functions. Conversely, the 12E3 mAb, which was the least potent inhibitor of [125I]TSH binding to hTSH-R transfected cells had no effect. A relationship was, therefore, established between the capacity of mAb to hTSH-R to inhibit [125I]hTSH binding and their ability to induce thyroid functions. PMID- 1733739 TI - Distribution and characterization of peptidylglycine alpha-amidating monooxygenase activity in the ovine brain and hypothalamo-pituitary axis. AB - The production of alpha-amidated peptide hormones from their glycine-extended precursors is catalyzed by the specific enzyme peptidylglycine alpha-amidating monooxygenase (PAM). In the present study, the distribution and subcellular localization of PAM activity in the sheep brain was examined and compared with known sites of amidated peptide synthesis and release. Of the brain regions assayed, the preoptic anterior and medial basal areas of the hypothalamus contained the greatest concentration of amidating activity. Lower concentrations (greater than 3-fold less) were found in the anterior and neurointermediate pituitary, median eminence, cerebral cortex, hippocampus, pons-medulla, and brainstem. Very low amounts of activity were present in the cerebellum and pineal gland. In most tissues tested, PAM activity was 40-75% higher in the membrane associated fraction than in the soluble fraction. In the hypothalamus, affinity constants were identical for both membrane-associated and soluble fractions, and ranged from 12.3-13.3 microM. Maximal velocity was higher in the membrane fraction (4.7-4.8 pmol/microgram.h) than in the soluble fraction (2.6-2.9 pmol/microgram/h). Levels of amidating activity in hypophysial-portal and jugular plasma were similar and were 20- to 25-fold lower than in hypothalamic extracts. Insulin-induced hypoglycemia did not significantly alter PAM levels in portal or peripheral plasma, suggesting that amidating activity is not released during this stress. These results indicate that the hypothalamus is the richest source of amidating activity in the sheep brain, and suggest that amidation of neurohypophysial and hypothalamic releasing peptides may occur before axonal transport, given the much lower levels in median eminence, neurointermediate pituitary, and portal plasma. PMID- 1733740 TI - Severe burns as a consequence of seizures in patients with epilepsy. AB - We report 10 seizure-related thermal injuries severe enough to require hospitalization in patients with epilepsy. Eight of the ten incidents were with patients who had had seizures with impaired consciousness two or more times a month. This suggests that seizure frequency is a risk factor and implies the importance of striving for optimal seizure control. Two burns each occurred from an electric iron, a hand-held hair dryer, and stove-top cooking. Minimizing these activities, especially in patients with frequent consciousness-altering seizures, may be useful. Three burns occurred while showering; these resulted in the most severe injuries, with hospital stays of 29, 30, and 41 days. Simple plumbing devices may have prevented these injuries. PMID- 1733741 TI - Acute intermittent porphyria and epilepsy: safety of clonazepam. AB - A young woman with acute intermittent porphyria (AIP) and juvenile myoclonic epilepsy began to have generalized tonic-clonic seizures (GTCs) at age 13. Subsequently, she had myoclonic seizures, which were often precipitated by visual stimulation, tended to occur in the morning, and sometimes evolved into GTCs. Valproate (VPA) resulted in a worsening of latent AIP, and treatment with a combination of phenytoin (PHT), carbamazepine (CBZ), and clonazepam (CZP) led to severe neuropathy of AIP and an electrolyte imbalance. These conditions were improved by water restriction, infusion of high doses of carbohydrates, and discontinuation of all antiepileptic drugs (AEDs) except for CZP. CZP appeared to be effective both in improving GTCs and myoclonic seizures and did not induce any symptoms of AIP. CZP may be porphyrogenic but can be used safely at a low dose for treatment of epilepsy in patients with AIP. PMID- 1733742 TI - Analysis of B10.D2 recombinant congenic mouse strains shows that audiogenic and beta-CCM-induced seizures depend on different genetic mechanisms. AB - The rate of occurrence of audiogenic seizures and seizures induced by the benzodiazepine receptor inverse agonist methyl-beta-carboline-3-carboxylate (beta CCM) were analyzed in several recombinant congenic strains of mice bred from B10.D2 and DBA/2J. Although both types of seizures have similar behavioral patterns and might involve GABAergic mechanisms, no correlation was observed between the occurrence of the two types of seizures across the strains, suggesting that these two types of seizures depend on different genetic mechanisms. PMID- 1733744 TI - Carbamazepine-induced eosinophilic colitis. AB - Severe watery diarrhea and eosinophilic colitis induced by carbamazepine (CBZ) has not been described previously. We report the first known case of CBZ-induced watery diarrhea and eosinophilic colitis in a 57-year-old man receiving CBZ for secondarily generalized tonic-clonic seizures that developed after a cerebral infarction. PMID- 1733743 TI - Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures. AB - ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically- and electrically-induced seizures in animals. The primary objective of this open add-on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline. PMID- 1733745 TI - Effect of vigabatrin on the electroencephalogram in rats. AB - Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG. PMID- 1733746 TI - Effects of vigabatrin on cognitive function and mood when used as add-on therapy in patients with intractable epilepsy. AB - Cognitive function and mood of patients with epilepsy who received 2 g/day vigabatrin (GVG) in addition to their usual antiepileptic drugs (AEDs) was assessed on two occasions: before start of treatment (baseline) and 4 weeks after start of treatment. A battery of selected psychological tasks measuring attention, mental speed, motor speed, central cognitive processing, and perceptuomotor performance was used, along with standardized, objective mood assessments. A comparison group (n = 15) of patients receiving stable medication was also tested to evaluate practice effects of the psychometric tests. Administration of 2 g/day GVG significantly decreased response time on a test of central cognitive processing ability (arithmetic). No adverse effect was noted on any other test of cognitive function or mood. PMID- 1733747 TI - Preliminary assessment of the efficacy of Org 6370 in photosensitive epileptic patients: paradoxical enhancement of photosensitivity and provocation of myoclonic seizures. AB - Photosensitivity has proved to be a useful model to study the acute effects of experimental antiepileptic drugs (AEDs). The photosensitivity range is usually diminished or even abolished after administration of a known or experimental AED. An increase in photosensitivity, an unexpected reaction, was found in four photosensitive epileptic patients after oral ingestion of 500, 100, or 50 mg of Org 6370. Moreover, the three patients receiving doses of 100 and 500 mg reported nausea, dizziness, restlessness, and an increase in spontaneous epileptic seizures (myoclonus and in one patient a generalized tonic-clonic convulsion). The side effects coincided with peak Org 6370 serum levels. Our findings indicate that in the photosensitivity model experimental drugs with proven anticonvulsant properties in animals may increase rather than decrease the degree of patient photosensitivity. Photosensitive patients may represent a special subgroup of epileptic patients and therefore need to be classified as such. PMID- 1733748 TI - Effects of seizures, kindling, and carbamazepine on sleep organization in cats. AB - We studied the relationships between epilepsy, sleep, and anticonvulsant drugs in kindled cats. No sleep alteration was present at midkindling. When the animals became fully kindled, a reduction in REM sleep percentage and the number of entries into REM sleep were observed compared to baseline. In addition, with further seizures, an increase in the percentage of wakefulness appeared, accompanied by a further reduction in the number of entries into REM sleep. It therefore seems that there is a progressive disruption of sleep, dependent on the increasing number of tonic-clonic generalized seizures. After a seizure-free interval, REM sleep and wakefulness returned to baseline values. A reduction in the percentage of stage II compared to baseline was found and remained as a long term effect of the kindling process. Acute administration of carbamazepine (CBZ) reduced the REM sleep percentage. This effect, paralleled by a reduction in the number of entries into REM sleep, was evident both at baseline and when the animals were fully kindled. After a large number of seizures, however, CBZ administration did not cause a further reduction in the already low percentage of REM sleep. Results are discussed with reference to previous literature. We propose a hypothesis of competition between seizure and REM sleep in the elimination of epileptogenic and hypnogenic factors. PMID- 1733750 TI - Effects of antiepileptic drugs on sperm motility of normal controls and epileptic patients with long-term therapy. AB - The in vitro effects of four antiepileptic drugs (AEDs) on human sperm motility were studied with a transmembrane migration method. Sperm motility of epileptic patients receiving chronic AED therapy was also investigated. Sperm motility was measured immediately after semen had been mixed with AED and after a 2-h preincubation at 37 degrees C. Both in vitro and in vivo studies demonstrated that AEDs inhibited sperm motility. When the drug effect was evaluated after the semen-AED mixture had been preincubated for 2 h, sperm motility was inhibited to 50% of control at concentrations of 1.59, 4.23, and 5.00 mM for phenytoin, carbamazepine, and valproate, respectively. Both with and without preincubation, phenobarbital, even up to 12.92 mM, did not inhibit the motility to less than 50% of the control. In the in vivo study, poor sperm motility was noted in epileptic patients with long-term AED therapy despite serum levels within the therapeutic range. Shorter duration of activity of spermatozoa was also observed in these patients. Interference with sperm membrane function by AEDs may be the underlying mechanism. PMID- 1733749 TI - Thyroid function with antiepileptic drugs. AB - Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733751 TI - Treatment of intractable childhood epilepsy with high-dose valproate. AB - Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage. PMID- 1733752 TI - Valproate metabolites in serum and urine during antiepileptic therapy in children with infantile spasms: abnormal metabolite pattern associated with reversible hepatotoxicity. AB - The purpose of this study was to identify abnormal metabolite patterns of valproate (VPA) as possible early indicators of VPA-induced liver toxicity. In a prospective study, we determined serum and urine levels of VPA metabolites by gas chromatography-mass spectrometry (GC-MS) during the course of therapy in 25 children treated for infantile spasms with high VPA doses (less than or equal to 100 mg/kg body weight/day). Most patients had similar metabolite profiles: The main metabolites in serum were the beta-oxidation products (2-en-VPA and 3-keto VPA) and the major diunsaturated metabolite 2,3'-dien-VPA. Glucuronide conjugates and the oxidation products represent the most abundant metabolites in urine. Other metabolites, including the potential hepatotoxin 4-en-VPA, were detected only in low concentrations. Two children had transiently aberrant metabolite profiles, indicating altered beta-oxidation, (levels of 2-en-VPA, 2,3'-dien-VPA, and 3-en-VPA were markedly increased) in connection with hepatomegaly and increased liver enzyme activities at a time when both had febrile infections and were receiving dexamethasone comedication. At no time were increased levels of 4 en-VPA or its derivatives detected. Establishing the VPA metabolite profile may aid in evaluation of patients who show signs and symptoms of liver dysfunction during VPA therapy. The present study shows that initial stages of hepatotoxicity reactions to VPA may be accompanied by characteristic changes in VPA metabolism; early detection of such abnormal metabolite patterns might decrease the risk of severe hepatic injury. PMID- 1733753 TI - Associations between risk factors for valproate hepatotoxicity and altered valproate metabolism. AB - The effects of three risk factors for valproate (VPA) hepatotoxicity (i.e., young age, polypharmacy, and high VPA serum level) on the metabolism of VPA to its monounsaturated metabolites [2-en-VPA (2-en), 3-en-VPA (3-en) and 4-en-VPA (4 en)] were investigated in 106 patients treated with VPA (56 cases of monotherapy and 50 cases of polytherapy). In the monotherapy group, there was a significant negative correlation between age and 4-en/VPA ratio. In the same group, the 4 en/VPA ratio showed a significant positive correlation with serum VPA level, while 3-en/VPA and 2-en/VPA ratios showed significant negative correlations. In patients greater than 10 years, the 4-en/VPA ratio was significantly higher, while the 2-en/VPA ratio was significantly lower in the polytherapy group than in the monotherapy group. Our results indicate that all three risk factors clearly increase the metabolic conversion of VPA to 4-en, the most toxic VPA metabolite, and that polytherapy and high VPA serum level result in the inhibited beta oxidative metabolism of VPA to 2-en. These altered VPA metabolic profiles are strikingly similar to the abnormal VPA metabolism previously reported in cases with fatal hepatic failure. Although VPA-induced fatal hepatotoxicity has been regarded as an idiosyncratic reaction, it is possible that these three factors enhance susceptibility to VPA hepatotoxicity by altering the metabolism of VPA. PMID- 1733754 TI - Valproate therapy induces von Willebrand disease type I. AB - To investigate the increased tendency of hemorrhage in patients receiving valproate (VPA) therapy, we studied coagulation parameters in 30 randomized children of a group of 83 children receiving antiepileptic drug (AED) therapy. Besides a reduction in fibrinogen concentration and platelet count, we observed a significant decrease in factor VIII-complex. A decrease in factor VIII:C was noted in 33%, a decrease in von Willebrand factor (vWF:Ag) was noted in 83% and a decrease in ristocetin-cofactor activity (vWF:Rcof) was noted in 66% of the children. We classified a von Willebrand syndrome type I in 67% of our patients receiving VPA therapy. Sixty-three percent of patients had a history of bleeding, and 23% had a prolonged bleeding time. We compared our results with those of a control group and of a group of patients with congenital von Willebrand disease (vWD), from which patients with multimer types II and III were excluded. Because coagulation parameters in patients with congenital vWD are similar to those receiving AED therapy, we designated the increased tendency to hemorrhage as VPA induced vWD. The decrease in coagulation parameters were not dependent on either VPA dose or period of administration. In patients receiving VPA therapy, this result must be considered, especially during surgical intervention and after traumatic events. PMID- 1733755 TI - Intractable diarrhea from carbamazepine. AB - Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug. PMID- 1733756 TI - The developmental profile of seizure genesis in the inferior collicular cortex of the rat: relevance to human neonatal seizures. AB - The ontogeny of seizure genesis within the inferior collicular cortex was characterized in rats ranging in age from 3 days old to adult. Brief electrical stimulation of the right inferior collicular cortex in 30-day-old rats evoked poststimulus wild running behavior that coincided with afterdischarge activity in the inferior collicular cortex but not in the adjacent occipital cortex. Similar electrical stimulation in 16-day-old rats produced poststimulus wild running and jumping behaviors, which also coincided with afterdischarge in the inferior collicular cortex. In 10- and 5-day-old rats, electrical stimulation of the inferior collicular cortex produced poststimulus locomotion and coincident afterdischarge activity, but unlike older rats the locomotor behaviors consisted of forelimb paddling, hindlimb treading, and rolling/curling movements of the torso. Identical behaviors can be electrically elicited in 3-day-old rats. Although many of the seizure characteristics appear to be similar among the different age groups, 5-day-old rats were more sensitive to low frequency stimulation than 16-day-old rats, who in turn were more sensitive than adult rats. Thus, the inferior collicular cortex is capable of generating seizure activity in rats as young as 3 days of age, providing a focal model of neonatal seizure genesis. PMID- 1733757 TI - Hippocampal pyramidal cell loss in human status epilepticus. AB - A pilot case-control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxia/ischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommer's sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls. PMID- 1733758 TI - High signal intensity on T2-weighted MRI correlates with hypoperfusion in temporal lobe epilepsy. AB - Single-photon emission computed tomography (SPECT) and [99mTc]HMPAO were used to assess the functional significance of nonspecific magnetic resonance imaging (MRI) abnormalities observed in patients with temporal lobe epilepsy and no focal lesion on CT scan. We studied 18 patients whose MRI was normal or showed high signal intensity on T2-weighted images (T2WIs) at the site of the EEG focus in 11 and 7 cases, respectively. EEG was monitored during regional cerebral blood flow (rCBF) study. Lateralized hypoperfusion was present in 7 of 17 interictal (41%) and in one postictal cases; it was located in the temporal lobe on the side of the EEG focus in all, and was significantly more frequent in patients with high signal intensity on T2WI (86%) than in patients with a normal MRI (18%). The degree of temporal perfusion asymmetry measured in each individual was higher in patients whose MRI was abnormal. PMID- 1733759 TI - Prognosis of epilepsy in newly referred patients: a multicenter prospective study of the effects of monotherapy on the long-term course of epilepsy. Collaborative Group for the Study of Epilepsy. AB - A cohort of 280 previously untreated epilepsy subjects (159 men and 121 women aged 2-81 years) recruited in 14 Italian centers were treated with antiepileptic drug (AED) monotherapy and followed for a median period of 48 months to investigate the rates of seizure remission (i.e., complete control), in general and with reference to various prognostic factors. The cumulative probability of achieving 1-year remission was 62% by 1 year after onset of treatment, 81% by 2 years, 92% by 3 years, and 98% by 5 years. The corresponding figures for 2- and 3 year remission at 5 years were 92 and 78%, respectively. Sixty-two patients (22.1%) had no remission period with monotherapy. Remission rates were significantly lower among patients with two or more seizure types and were inversely correlated to the number of seizures before treatment. The rate of seizure relapses during the first year of follow-up appear to correlate to the risk of developing refractory epilepsy (i.e., with no remission). PMID- 1733760 TI - Febrile seizures: clinical characteristics and initial EEG. AB - We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were classified as paroxysmally abnormal if they contained spikes, sharp waves, or spike-wave complexes considered abnormal for age. In all, 22% of the 676 children had an abnormal initial EEG. The most common basis for classification as abnormal was spike-wave complexes greater than 3 Hz; the next most common basis was the presence of spikes. Birth weight, gender, accompanying illness, and family history of seizures, and whether the index seizure was single or multiple were not associated with differences in rate of abnormal EEG. Clinically focal index seizures and longer duration were associated with EEG abnormality. Number of previous febrile seizures was associated with an increasing rate of EEG abnormality, from 18% in children with no previous seizures to 63% in those with four or more previous seizures. Age at EEG was linearly related to likelihood of paroxysmal EEG abnormality, both for the total cohort and for the 376 children with no previous seizures. In the total cohort, logistic regression identified leading predictors of abnormal initial EEG to be older age, number of previous febrile seizures, preexisting motor abnormality, and focal seizures. For children with a first febrile seizure, leading predictors were focal seizure, older age, and preexisting motor abnormality. PMID- 1733761 TI - Kufs' disease presenting as progressive dementia with late-onset generalized seizures: a clinicopathological and electrophysiological study. AB - A 32-year-old woman presented with increasing motor difficulties and memory disturbances. Neurological examination only showed mild cerebellar and extrapyramidal symptoms, whereas neuropsychological evaluation disclosed severe cognitive changes consistent with dementia. Her motor and mental status progressively deteriorated until death, which occurred 5 years after the first admission. One year before death, while she was almost bedridden, symptoms of myoclonic epilepsy first appeared, with frequent generalized seizures and generalized myoclonus, occurring especially upon sensory stimulation or passive joint movements. Pathological examination showed neuronal inclusions typical of Kufs' disease. This case, with primary progressive dementia and late-onset myoclonic epilepsy, differs from previously reported cases. Three special electrophysiological features were abnormal, "giant", evoked potentials; unusually marked photosensitivity; and seizure induction by any sensory stimulation. PMID- 1733762 TI - A study of unilateral brief focal atonia in childhood partial epilepsy. AB - We studied unilateral brief focal atonia (BFA) in seven patients with childhood partial epilepsy. BFA was observed as a transient dropping of one arm lasting from 100 to 150 ms when patients were asked to keep both arms outstretched in front of the body. Close examination using simultaneous video-polygraphic recordings showed dropping of the arm to correspond exactly with a single sharp and slow wave complex arising from the contralateral centrotemporoparietal region. The BFA occasionally would progress to atonic seizures or atonic absence seizures, when the localized epileptic discharge evolved into generalized discharges. In one patient we found a positive correlation between the intensity of BFA and the amplitude of the contralateral epileptic discharges. A higher amplitude corresponded to more pronounced BFA and a lower amplitude to less pronounced BFA. These results led us to conclude that the apparently interictal single sharp and slow wave complex in the rolandic region may inhibit contralateral motor control, thus producing BFA that corresponds with the spike amplitude. PMID- 1733763 TI - Pattern-sensitive epilepsy: genetic aspects in two families. AB - We report two families in which five members (three in one and two in the other) suffer from pattern-sensitive epilepsy. In all affected members seizures were induced by environmental visual patterned stimuli. Diagnosis was confirmed by neurophysiological studies, including EEG with pattern and intermittent light stimulation and visual evoked potentials. The role of genetic aspects and the relationship between this form of reflex seizures and photosensitive epilepsy are emphasized. PMID- 1733764 TI - Game-playing epilepsy. AB - A 25-year-old woman with documented generalized seizures evoked by playing checkers was given a battery of psychological tests as well as a series of cognitive and non-game-related tasks during a session of intensive EEG-video monitoring. Generalized epileptiform discharges during each task, as well as during intervals of checkers playing, were quantified to determine possible triggering factors. Previous reports have discussed the roles of attention, concentration, stress, thinking, and spatial processing in similar cases. Our analysis showed significant activation of the EEG only with tasks involving strategic thinking, i.e., considering a sequence of moves based on evaluating the consequences of previous moves. PMID- 1733765 TI - Effects of a broad-spectrum behavioral medicine treatment program on children with refractory epileptic seizures: an 8-year follow-up. AB - We present an 8 year follow-up on a group of children with refractory epileptic seizures who participated in the early 1980s in a controlled group study on the effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures. In the original study, 18 children were divided into three groups: behavior modification group, attention control group, and control group. The purpose was to investigate the effects of a learning-based treatment program superimposed on a regular medical treatment program. Also, the effects of professional attention were evaluated. At the 10 week and 1 year follow-ups, only the group receiving the behavior modification intervention had a significantly reduced rate of seizure index. The present study investigates these same children 8 years later using the same methods of investigation for an additional 10 week period. The results indicate that a significant reduction in seizures was obtained only for the behavior modification group at the 8 year follow-up. PMID- 1733766 TI - Time-varying and static magnetic fields act in combination to alter calcium signal transduction in the lymphocyte. AB - We have tested the hypothesis that extremely low frequency (ELF) time-varying magnetic fields act in combination with static magnetic fields to alter calcium signalling in the lymphocyte. Results indicate that a 60-min exposure of thymic lymphocytes at 37 +/- 0.05 degrees C to a 16 Hz, 421 mG (42.1 microT) magnetic field simultaneously with a colinear static magnetic field of 234 mG (23.4 microT) (a.c./d.c. field intensity ratio = 1.8) inhibits calcium influx triggered by the mitogen Concanavalin A. Significantly, resting lymphocytes do not respond to the fields, thus, only mitogen-activated cells undergoing calcium signalling exhibit a field response. These results indicate that signal transduction involving calcium is an important biological constraint which operates to mediate this field interaction. Additional split field exposures show that the presence of the a.c. field or the d.c. field alone does not produce an effect. This is consistent with a proposed parametric resonance theory of interaction of low intensity magnetic fields with biological systems (L.L. Lednev (1991) Bioelectromagnetics 12, 71-75), which predicts the occurrence of biological effects at specific values for the frequency and field intensity of the ELF and static magnetic fields. PMID- 1733767 TI - Retroviral-mediated transfer of a dystrophin minigene into mdx mouse myoblasts in vitro. AB - We have demonstrated expression of a 6.3 kb Becker muscular dystrophy (BMD) human dystrophin cDNA following retroviral-mediated transduction of cultured myoblasts from the dystrophin-deficient mdx mouse. The truncated dystrophin protein was localised to the sarcolemma of differentiated myotubes by antibodies against the C-terminus of the molecule, and produced an identical immunostaining pattern to that observed in control myotubes expressing normal endogenous dystrophin. These results indicate that retroviral-mediated gene transfer may be useful for experimental in vivo studies on the complementation of dystrophin gene mutations. PMID- 1733768 TI - Resonance effects in strongly exothermic long-range electron transfer and their possible implications for the behaviour of site-directed mutant proteins. AB - Long-range electron transfer investigations of hemoproteins, blue copper and iron sulphur proteins frequently rest on electronically excited metal centres. When the excitation energy approaches the oxidation or reduction potentials of intermediate residues the superexchange view normally used, however, fails and a variety of new dynamic features arise. These all involve population of the intermediate cation or anion residue states which can be partially or wholly vibrationally relaxed. We discuss suitable views and a new theoretical formalism for these phenomena. We also note some important implications for site-directed mutagenesis in long-range, strongly exothermic electron transfer processes. PMID- 1733769 TI - Specific inhibition of binding of antistasin and [A103,106,108] antistasin 93-119 to sulfatide (Gal(3-SO4)beta 1-1Cer) by glycosaminoglycans. AB - Leech-derived antistasin is a potent anticoagulant and antimetastatic protein that binds sulfatide (Gal(3-SO4)beta 1-1Cer) and sulfated polysaccharides. In this study, the synthetic fragment [A103,106,108] antistasin 93-119, which corresponds to the carboxyl terminus, showed specific and saturable binding to sulfatide. Binding was competitively blocked by glycosaminoglycans (GAGs) in the order: dextran sulfate 5000 congruent to dextran sulfate 500,000 greater than heparin greater than dermatan sulfate much greater than chondroitin sulfates A and C. This rank order of inhibitory potency was identical to that observed with whole antistasin. We suggest that residues 93-119 of antistasin represent a critical domain for binding GAGs and sulfated glycolipids. PMID- 1733770 TI - Low resolution solution structure of the Bacillus subtilis glucose permease IIA domain derived from heteronuclear three-dimensional NMR spectroscopy. AB - A low resolution solution structure of the IIA domain of the Bacillus subtilis phosphoenolpyruvate-sugar phosphotransferase system (PTS) glucose permease has been determined using 945 inter-residue and 724 intra-residue distance constraints derived from three-dimensional 15N and 13C edited NOESY spectra. A total of 15 structures was generated using distance geometry calculations. The protein is comprised of 13 beta-strands forming an antiparallel beta-barrel. The average backbone atomic RMS deviation about the average distance geometry structure for the beta-sheet residues is 1.1 A. The conformations of the loop regions between the beta-strands are less well determined. Backbone distance constraints obtained during the process of sequential assignment were insufficient to correctly calculate the polypeptide fold. PMID- 1733771 TI - A study of D52S hen lysozyme-GlcNAc oligosaccharide complexes by NMR spectroscopy and electrospray mass spectrometry. AB - The production of a mutant hen lysozyme is described in which Asp-52, one of the catalytically important residues, is replaced by Ser. The mutant enzyme has very low catalytic activity but NMR studies show that its structure is closely similar to that of the wild-type protein. NMR experiments also show that well defined complexes are formed with GlcNAc4 and GlcNAc6 bound in the active site of the mutant enzyme. These complexes have been examined using electrospray mass spectrometry (ESMS). The most intense peaks arise from the uncomplexed protein indicating that dissociation takes place in the mass spectrometer under the conditions used here. Peaks from minor species corresponding to complexes between the protein and the oligosaccharides are, however, also observed. The possibility that the latter arise from novel covalent enzyme-saccharide complexes is discussed. PMID- 1733772 TI - Anhydrosubtilisin-catalyzed peptide synthesis. AB - Anhydrosubtilisin was found to be a good catalyst for the peptide synthesis though its hydrolytic activity was fully inhibited. Amino acid (peptide) p chlorophenyl ester (acyl donor) was coupled with amino acid (peptide) amide in the presence of the modified enzyme. The method did not afford by-products resulting from the hydrolysis of the acyl donor. This is the most advantageous characteristic of the method, since the hydrolysis of the acyl donor is unavoidable for the methods using catalytically active proteases. Anhydrosubtilisin was further shown to be useful for the fragment condensation of peptides. PMID- 1733773 TI - Oleoylamine and sphingosine stimulation of phosphatidylserine synthesis by LA-N-2 cells is protein kinase C independent. AB - The presence of sphingosine and oleoylamine in the culture medium of LA-N-2 cells stimulated the incorporation of [3H]serine into its corresponding phospholipid, phosphatidylserine (PtdSer). The optimum stimulation for sphingosine and oleoylamine were 50 microM and 100 microM, respectively. Oleoylamine increased the incorporation of [3H]serine over 6-fold while sphingosine increased the incorporation of [3H]serine over 2.5-fold. The amount of radioactivity found in water-soluble components and in protein was similar to that found with control LA N-2 cells. The incorporation of [3H]choline and [3H]ethanolamine into their corresponding phospholipids were decreased in the presence of either oleoylamine or sphingosine. A protein kinase C (PKC) activator, DiC8, and a PKC inhibitor, H7, did not influence the enhanced phosphatidylserine formation by sphingosine and oleoylamine. In addition, there were no differences in the stimulatory effect of sphingosine and oleoylamine discernable between PKC down-regulated cells or controls. These observations indicate that this oleoylamine and sphingosine mediated enhanced phosphatidylserine synthesis is PKC-independent. PMID- 1733774 TI - The precursor form of the rat liver non-specific lipid-transfer protein, expressed in Escherichia coli, has lipid transfer activity. AB - The cDNA encoding the precursor form of non-specific lipid-transfer protein (pre nsL-TP) from rat liver was cloned into the expression vector pET3d. The resulting plasmid was transformed to the Escherichia coli strain BL21(DE3). After induction of the bacteria with isopropyl-beta-D-thiogalactopyranoside (IPTG) pre-nsL-TP was purified from the bacterial lysate by anion exchange chromatography followed by gelfiltration. From 11 of culture, 6-7 mg of pre-nsL-TP was obtained, equal to approximately 7% of the cytoplasmic protein. By use of a fluorescence lipid transfer assay, pre-nsL-TP was found to have lipid transfer activity identical to mature nsL-TP. PMID- 1733775 TI - Alteration of the proximal bond energy in the unliganded form of the homodimeric myoglobin from Nassa mutabilis. Kinetic and spectroscopic evidence. AB - CO binding kinetics to the homodimeric myoglobin (Mb) from Nassa mutabilis has been investigated between pH 1.9 and 7.0. Protonation of the proximal imidazole at low pH (less than or equal to 3.0) and the consequent cleavage of the HisF8NE2 Fe proximal bond brings about a approximately 20-fold increase of the second order rate constant for CO binding. This process displays a pKa = 4.0 +/- 0.2, significantly higher than that observed in all other deoxygenated hemoproteins investigated up to now. Such a feature underlies a decreased energy for the HisF8NE2-Fe proximal bond in the unliganded form and it also appears supported by resonance Raman spectroscopy in the low frequency region of the Fe(II) deoxygenated hemoprotein. Further, the pH-rate profile of N. mutabilis Mb, like that of the homodimeric hemoglobin (Hb) from Scapharca inaequivalvis (Coletta, M., Boffi, A., Ascenzi, P., Brunori, M. and Chiancone, E. (1990) J. Biol. Chem. 265, 4828-4830), can be described only by assuming a concerted proton-linked transition with n = 1.8 +/- 0.1. Such a characteristic suggests, also on the basis of the amino acid sequence homology between N. mutabilis Mb and S. inaequivalvis Hb in the region forming the subunit interface, that the interaction mechanism is similar for the two homodimeric proteins, and drastically different Hb in the region forming the subunit interface, that the interaction mechanism is similar for the two homodimeric proteins, and drastically different from that operative in other hemoproteins. PMID- 1733776 TI - Glycinebetaine stabilizes the association of extrinsic proteins with the photosynthetic oxygen-evolving complex. AB - The photosynthetic oxygen-evolving activity of the photosystem 2 complex, prepared from spinach, was labile when the complex was exposed to high-salt conditions under which the extrinsic proteins were dissociated from the complex. Glycinebetaine prevented the dissociation of the 18-kDa and the 23-kDa extrinsic proteins from the photosystem 2 complex in the presence of 1 M NaCl. It also prevented the dissociation of the 33-kDa extrinsic protein from the complex in the presence of 1 M MgCl2 or 1 M CaCl2. The oxygen-evolving activity of the photosystem 2 complex was stabilized by glycinebetaine when the complex was subjected to treatment with NaCl and MgCl2. PMID- 1733777 TI - Shortened cecropin A-melittin hybrids. Significant size reduction retains potent antibiotic activity. AB - We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15 residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes. PMID- 1733778 TI - Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclase. AB - We report the molecular cloning of human gene (S31) containing an open reading frame of 1095 nucleotides, which encodes a protein of 365 amino acids. The encoded protein contains seven hydrophobic putative transmembrane domains considered the hallmark of G protein-coupled receptors. The amino acid sequence shows highest homology to receptors for serotonin (5-hydroxytryptamine). Expression of this receptor in murine Ltk- cells conferred upon these cells the ability to respond to serotonin by inhibition of adenylyl cyclase. No response was observed to isoproterenol, epinephrine, histamine, dopamine or melatonin in the transfected cells. We propose that the human gene S31 encodes a novel serotonin receptor. PMID- 1733779 TI - Puromycin reaction for the A site-bound peptidyl-tRNA. AB - AcPhe2-tRNA(Phe) synthesized in 70S ribosomes after consecutive binding of AcPhe tRNA(Phe) at the P sites and EF-Tu-directed binding of Phe-tRNA(Phe) at the A sites is able to react quantitatively with puromycin in the absence of EF-G. A detailed study of the kinetics of the puromycin reaction, its comparison with that of spontaneous translocation, the use of antibiotic viomycin as an effective inhibitor of spontaneous translocation revealed that, besides spontaneous translocation, this peptidyl-tRNA could react with puromycin being located at the A site. This leads to the conclusion that the transpeptidation reaction per se triggers conformational changes in the ribosomal complex bringing the 3'-end of a newly synthesized peptidyl-tRNA nearer to the peptidyl-site of the peptidyltransferase center. This is detected functionally as the ability of such an A site bound peptidyl-tRNA to react with puromycin. This reaction is highly pronounced at elevated (25 degrees C) temperature but can be hardly detected at 0 degrees C. PMID- 1733780 TI - Glucose has to be phosphorylated to activate glycogen synthase, but not to inactivate glycogen phosphorylase in hepatocytes. AB - 2-Deoxyglucose and 5-thioglucose, in the same fashion as glucose, cause the inactivation of the rat hepatocyte glycogen phosphorylase and the activation of glycogen synthase. However, 6-deoxyglucose and 1,5-anhydroglucitol inactivate phosphorylase without increasing the activation state of glycogen synthase. With 3-O-methylglucose no changes in the activity of these enzymes occurred. These results prove that while glucose is the molecule that triggers the inactivation of phosphorylase, glucose 6-phosphate is the signal for glucose synthase activation and that a metabolite control of the activation state of glycogen synthase is operative in hepatocytes. PMID- 1733781 TI - Nitrendipine is a potent inhibitor of the Ca(2+)-activated K+ channel of human erythrocytes. AB - Nitrendipine, a classical blocker of L-type Ca2+ channels, is shown to be a potent inhibitor of the Ca(2+)-activated K+ channel of human erythrocytes. In erythrocytes suspended in a solution with physiological Na+ and K+ concentrations and in which the channel was activated using the Ca2+ ionophore ionomycin, nitrendipine inhibited K+(86Rb+) influx with an I50 of around 130 nM. Similar results were obtained for K+(86Rb+) efflux, and for K+(86Rb+) influx into cells suspended in a high-K+ medium. PMID- 1733782 TI - A plant homologue to mammalian brain 14-3-3 protein and protein kinase C inhibitor. AB - We have isolated cDNA clones of Spinacea oleracea L. and Oenothera hookeri of 930 and 1017 base pairs, respectively. The open reading frame deduced from the Oenothera sequence codes for a protein of a calculated molecular mass of 29,200. The primary amino acid sequence exhibits a very high degree (88%) of homology to the 14-3-3 protein from bovine brain, and protein kinase C inhibitor from sheep brain. Subsequently the plant protein was partially purified from leaf extract. The partially purified plant protein inhibited protein kinase C from sheep brain in a heterologous assay system. The active fraction consisted of 5-6 different polypeptides of similar molecular size. One of these proteins crossreacted with a peptide-specific antibody against protein kinase C inhibitor protein from sheep brain. PMID- 1733783 TI - Okadaic acid inhibits angiotensin II stimulation of Ins(1,4,5)P3 and calcium signalling in rat hepatocytes. AB - OKA2 and CL-A significantly inhibit the ability of angiotensin II, ATP and vasopressin to raise [Ca2+]i in rat hepatocytes, with a partial inhibition of the initial spike, and a complete inhibition of the following plateau. In contrast, the [Ca2+]i response to thapsigargin, which releases intracellular calcium stores through a mechanism independent of inositol phosphates, is much less affected. The ability of angiotensin II to stimulate Ins(1,4,5)P3 production is also reduced by OKA, with kinetics consistent with the inhibited [Ca2+]i response. Since OKA and CL-A are potent and selective inhibitors of phosphoprotein phosphatases, these results provide further evidence that agonist-stimulated Ins(1,4,5)P3 signalling can be inhibited by protein phosphorylation. PMID- 1733784 TI - Kinetic interpretations of active site topologies and residue exchanges in Drosophila alcohol dehydrogenases. AB - 1. A comparison of full and partly sequenced Adhs from various Drosophila species reveal that 127 of their 253-255 positions are identical (50% identity). 2. Fifty six of the 115 C-terminal amino acids building up the alcohol binding region differ. In spite of the large differences in primary structure of the alcohol binding region in the Adh enzyme in distantly related Drosophila species, the substrate specificity and stereospecificity have been retained. The topology of the alcohol binding region has been largely conserved during evolution. 3. The primary structures of the alcohol dehydrogenases (Adh) in the Sophophora subgenus is distinguished by few amino acid exchanges, and kinetic and activity parameters show that those at positions 14, 82, 192 and 214 are directly or indirectly involved in coenzyme binding. 4. In these non-metallo Adhs, a tyrosine has been tentatively identified as a nucleophilic catalyst of the hydride transfer step. The three tyrosines at positions 63, 152 and 178 are conserved among the Drosophila alcohol dehydrogenases. PMID- 1733785 TI - Insulin: signal transmission and short-term effects on the cytoskeleton and protein synthesis. PMID- 1733786 TI - The role of cellular oncogenes in myogenesis and muscle cell hypertrophy. PMID- 1733787 TI - Selective chemical modification of amino acid residues in the flavin adenine dinucleotide binding site of NADPH-ferredoxin reductase. AB - 1. An apo-NADPH-ferredoxin reductase was prepared from holo-NADPH-ferredoxin reductase (EC 1.18.1.2) from bovine adrenocortical mitochondria. 2. Amino acid residues of the apo-reductase were modified selectively, to identify the FAD binding site of the reductase, with chemical reagents such as diethylpyrocarbonate, 5,5'-dithiobis(2-nitrobenzoate), tetranitromethane, pyridoxal 5'-phosphate, p-nitrophenylglyoxal, diisopropylfluorophosphate and N bromosuccinimide. The binding of FAD to the apo-reductase was measured as quenching of the fluorescence of FAD caused by the binding between apo-reductase and FAD. The quenching was blocked when the apo-reductase was modified with diethylpyrocarbonate and restored on the addition of hydroxylamine. 3. The blocking of the quenching occurred in a competitive manner as to FAD in the presence of diethylpyrocarbonate. However, when the apo-reductase was modified with 5,5'-dithiobis(2-nitrobenzoate), the blocking of the quenching occurred in a non-competitive manner. 4. These results suggested that a histidyl residue of the apo-reductase is essential for the binding of FAD to the reductase. This was confirmed by amino acid sequencing of the modified apo-reductase. PMID- 1733788 TI - Bovine brain cathepsin D: inhibition by pepstatin and binding to concanavalin A. AB - 1. Cathepsin D from bovine brain has been purified 1100-fold in 46% recovery. Three isozymes are present with pI (+/- 0.05) = 6.10, 6.30 and 6.40. 2. The isozymes are single polypeptide chains with apparent Mr = 42,000 and are similar with respect to substrate binding and cleavage; the pH-optimum is 3.5 with virtually no activity at neutral pH. 3. Pepstatin inhibits the enzyme and kinetic data are consistent with a "tight binding" mechanism. 4. The dissociation constant for the concanavalin A-enzyme complex is Kd = 19 nM at pH 5.0. 5. Under conditions where 90% of the enzyme is bound to soluble concanavalin A, full enzymatic activity is observed. PMID- 1733789 TI - Isolation, biochemical characterization and crystallization of the p15gag proteinase of myeloblastosis associated virus expressed in E. coli. AB - 1. The p15gag proteinase responsible for the processing of the polyprotein precursor of the myeloblastosis associated virus was obtained by a recombinant technique in an E. coli expression system. The massive expression of the intentionally truncated precursor (Pr25lac-delta gag) was accompanied by its structurally correct processing. 2. Three procedures for the purification of the recombinant proteinase from both the cytoplasmic fraction and the inclusion bodies were developed. 3. The purified proteinase was compared with the authentic proteinase isolated from MAV virions by N-terminal sequence analysis and amino acid analysis, molecular weight determination, reverse-phase HPLC and FPLC elution profiles, electrophoretic mobility and isoelectric point determination, and activity assays with proteins and synthetic substrates. The identity of both enzymes was shown. 3. Contrary to reported data, the amino acid sequence of the p15gag proteinase differs from the sequence of the homologous Rous sarcoma virus proteinase in one residue only, as follows from cDNA sequencing. 4. Crystallization of the proteinase from a citrate-phosphate buffer at pH 5.6 afforded hexagonal crystals which diffracted well as 2.3 A without deterioration. PMID- 1733790 TI - Influence of dietary sorbose on lipogenesis in gold thioglucose-injected obese mice. AB - 1. The influence of dietary sorbose on food intake and fatty acid synthesis of the liver and epididymal white adipose tissue (EWAT) was investigated in gold thioglucose (GTG)-injected obese mice from 12 to 14 weeks of age. 2. Sorbose was supplemented to a semi-purified diet at a level of 200 g/kg diet at the expense of sucrose. 3. On the last day of the experiment, fatty acids synthesis in the liver and EWAT was measured using an i.p. injection [1-14C]sodium acetate. 4. The decreases in body weight and food intake by dietary sorbose in GTG-injected obese mice were greater than those in control mice. 5. Lipid content and fatty acid synthesis in the liver and EWAT of control mice were not influenced by dietary sorbose. 6. In GTG-injected obese mice, the reduction of food intake by dietary sorbose suppressed fatty acid synthesis and lipid deposition in both liver and EWAT. PMID- 1733791 TI - Rat pulmonary lipoxygenase: dioxygenase activity and role in xenobiotic metabolism. AB - 1. Dioxygenase activity and the ability of pregnant rat lung lipoxygenase to oxidize xenobiotics were examined in vitro under a variety of experimental conditions. 2. More than 90% of the dioxygenase activity towards linoleic acid in the lung homogenate was found to be associated with the cytosolic fraction. The cytosolic enzyme exhibited pH optima at 6.5 and 9.5, the activity being two-fold greater at pH 9.5. To observe maximal dioxygenase activity (about 0.7 mumol of 13 hydroperoxylinoleic acid formed/min per mg protein) at pH 9.5, the presence of 6.0 mM linoleic acid was required. 3. Benzidine oxidation occurred at maximal rate of pH 6.5 when the reaction medium contained 1.0 mM benzidine and 13.5 mM linoleic acid. All eight xenobiotics tested were oxidized at significant rates by the lung cytosolic lipoxygenase. 4. Both dioxygenase activity and benzidine oxidation were inhibited by the inhibitors of lipoxygenase, viz. nordihydroguaiaretic acid, BHT, caffeic acid, esculetin, and gossypol, in a concentration-dependent manner. 5. The results suggest that oxidation of xenobiotics by lipoxygenase may be an important pathway of metabolism in the mammalian lung. PMID- 1733792 TI - Behaviour of butyrylcholinesterase in the intestinal epithelial cells of starved and refed rats. AB - 1. The activity and the molecular characteristics of butyrylcholinesterase were studied in the epithelial cells of the following intestinal segments: duodenum, jejunum, ileum, caecum and colon of starved and refed rats. 2. After starvation, the specific activity of the enzyme is found to increase in the jejunum. The same level of activity was maintained after refeeding. No notable changes were observed in the other intestinal segments after either starvation or refeeding. 3. The behaviour of aminopeptidase, a well-characterized intestinal enzyme, is comparable to that of butyrylcholinesterase, except in the duodenum where the aminopeptidase activity is increased after refeeding. 4. In this cell type, BuChE is found only in its globular forms (G1, G2 and G4). Starvation resulted in a higher value of the sedimentation coefficient of the ileal G2 form, suggesting the existence of a complex between the enzyme and non-cholinesterase components. 5. After refeeding, the sedimentation profile was similar to that of control. PMID- 1733793 TI - Changes of malic enzyme activity in the developing rat brain are due to both the increase of mitochondrial protein content and the increase of specific activity. AB - 1. The pattern of NADP-linked malic enzyme activity estimated in the whole brain homogenate did not parallel that found in liver of developing rat. 2. Studies on intracellular distribution of malic enzyme in brain showed that the mitochondrial enzyme increased about three-fold between 10th and 40th day of life. Thereafter, a slow gradual increase to the adult level was observed. 3. The extramitochondrial malic enzyme from brain, like the liver enzyme, increased at the time of weaning, although to a lesser extent. At day 5 the brain malic enzyme was equally distributed between mitochondria and cytosol. 4. During the postnatal development, the contribution of the mitochondrial malic enzyme in the total activity was increasing, reaching the value approx. 80% at day 150 after birth. 5. The increase with age of the malic enzyme specific activity was observed in both synaptosomal and non-synaptosomal mitochondria, the changes in the last fraction being more pronounced. 6. The activity of citrate synthase developed markedly between 10-40 postnatal days, increasing about five-fold, while the specific activity of the enzyme did change neither in the synaptosomal nor in non synaptosomal mitochondria at this period. 7. We conclude that the changes in malic enzyme activity in the developing rat brain are mainly due both to the increase of mitochondrial protein content and to the increase of specific activity of the mitochondrial malic enzyme. PMID- 1733794 TI - Determination of the amino acid sequence of adreno-ferredoxin from sheep adrenocortical mitochondria. AB - 1. An adreno-ferredoxin was purified from sheep adrenocortical mitochondria. 2. Its amino acid composition and amino acid sequence were determined chemically. 3. It was found to be composed of 127 amino acid residues, including two tyrosyl residues. 4. The amino acid sequences of various ferredoxins of the two iron and two sulfur type were compared with respect to amino acid homology. PMID- 1733795 TI - Molecular cloning and nucleotide sequences of bovine hepato-ferredoxin cDNA; identical primary structures of hepato- and adreno-ferredoxins. AB - 1. The ferredoxin from bovine liver mitochondria, so-called hepatoredoxin, was purified and characterized as to its molecular weight, optical absorption spectrum and amino acid composition. 2. These properties were found to be very similar to those of adreno-ferredoxin. 3. To clarify the molecular basis of tissue specificity, the ferredoxin clones were obtained from a bovine liver library and the cDNA sequence of hepato-ferredoxin was determined. 4. The nucleotide sequence of hepato-ferredoxin clone was found to be identical to that of adreno-ferredoxin clone except for a single nucleotide in the 3' non translated region. 5. Identical amino acid sequence of the two ferredoxins was confirmed by determining the partial amino acid sequence of the purified hepato ferredoxin. 6. The results indicated that the organ specific activity of purified ferredoxin could not be explained by the different primary structure nor different RNA processing. 7. Other factors may be involved in the tissue specific properties of ferredoxins. PMID- 1733796 TI - Inhibition of aspartic proteinases by synthetic peptides derived from the propart region of human prorenin. AB - 1. Five synthetic peptides which together spanned the propart segment of human prorenin were tested for their ability to interact with human renin, pepsin, gastricsin, cathepsin D, cathepsin E, calf chymosin and the aspartic proteinase from Endothia parasitica. 2. While two peptides showed no significant effect with any of the enzymes, a further two were cleaved by several enzymes. 3. Only one (corresponding to the 32P-43P residues in the propart sequence) acted as a weak competitive inhibitor of most of the enzymes. PMID- 1733797 TI - Strong ionic interactions between mucins and two basic proteins, mucus proteinase inhibitor and lysozyme, in human bronchial secretions. AB - 1. Mucins were isolated from sputum from a patient with chronic bronchitis and subjected to two different preparation procedures. 2. In the first procedure, CsBr density-gradient centrifugation gave rise to two well-separated fractions. Mucins recovered in the high-density fraction still contained mucus proteinase inhibitor (MPI) and lysozyme (LSZ). 3. Mucins were purified after a second step of CsBr density-gradient centrifugation or after gel-filtration chromatography with a buffer of high ionic strength, containing 0.5 M NaCl. 4. In the second procedure, trichloroacetic acid treatment of whole sputum followed by cation exchange chromatography allowed the obtention of a non-retained fraction composed of mucins. 5. Gel-filtration in buffer containing 0.5 M NaCl, allowed the release of MPI and LSZ from mucins, thus confirming that interactions still occurred between those components. 6. The chemical compositions of the mucins isolated by the two above procedures were quite similar. 7. These data support the hypothesis of the existence of ionic interactions between basic amino acid residues of MPI and LSZ and acid residues of the carbohydrate chains of mucins in the secretions of the large airways. 8. These interactions could play a role in the protection of mucins against proteolysis and consequently in the maintenance of rheological properties of the mucus gel in disease. PMID- 1733798 TI - Bacterial lipopolysaccharide stimulates phospholipid synthesis and phosphatidylcholine breakdown in cultured human leukemia monocytic THP-1 cells. AB - 1. De novo synthesis of phospholipid and its catabolism in human leukemia monocytic THP-1 cells were investigated. 2. Radiolabelled precursors: [methyl 3H]chloride, [1,2-14C]ethanolamine and myo-[2-3H]inositol were readily incorporated into CHCl3-MEOH extractable lipid fraction as a function of time. 3. The radiolabels derived from choline, ethanolamine and inositol were preferentially incorporated into PC, PE and PI fraction, respectively. The data indicate that de novo PL synthesis takes place, and the CDP-choline pathway is operative as a major pathway for PC synthesized in THP-1 cells. 4. Bacterial endotoxin dose-dependently stimulated the incorporation of radiolabelled precursors. Approximately 50% stimulation in PC and PE synthesis was obtained in 20 hr, while the incorporation of [3H]inositol was rapidly stimulated by 170% within 4 hr, and the stimulation declined drastically thereafter. 5. LPS did not alter the radiolabel distribution into PL in any of the three cases. 6. In pulse chase studies, the cells prelabelled with radioactive PL were exposed to LPS (1 micrograms/ml). The breakdown of PC was enhanced about 30% within the first 2 hr followed by a stimulated PC synthesis observed in the next 4 hr. In contrast, LPS did not induce the hydrolysis of PE and PI. 7. The data indicate that LPS produces a broad spectrum of stimulatory effects on PL synthesis and selectively stimulates the hydrolysis of PC via phospholipase C/D reaction in THP-1 cells. PMID- 1733799 TI - A comparative study of the biological properties of venoms of some old world vipers (subfamily viperinae). AB - 1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 30 samples of venoms from nine species (12 taxa) of the old world vipers (Subfamily Viperinae) including snakes from the genera Bitis, Causus, Cerastes, Echis, Eristicophis and Pseudocerastes, were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. Examination of the biological properties of the venoms of the Viperinae tested indicates the presence of common venom biological characteristics at the various phylogenic levels. 3. Venoms of most species of the Viperinae examined exhibited characteristic biological properties at the species level, and this allows the differentiation of the Viperinae species by differences in their biological properties. 4. Particularly useful for this purpose, are the effects of venom on kaolin-cephalin clotting time of platelet poor rabbit plasma and the Sephadex G 75 gel filtration pattern and arginine ester hydrolase activity of the venom. PMID- 1733800 TI - HLA and insulin-dependent diabetes. A protective perspective. AB - This article presents a model for the HLA effect in insulin-dependent diabetes mellitus (IDDM) that is almost the mirror image of a model suggested by Nepom. In the Nepom model, the products of certain HLA alleles are associated with IDDM because they bind and present a specific peptide or peptides so as to induce an immune response to pancreatic beta-cells; certain other alleles can protect against IDDM if they compete strongly for binding of the diabetogenic peptide. My model focuses instead on the failure of the immune system to maintain tolerance to pancreatic beta-cells. I suggest that the HLA alleles negatively associated with IDDM (e.g., DR2 and DQw1) produce products with high affinity for certain beta-cell peptide or peptides needed to establish and maintain tolerance to beta cells, whereas the alleles that are common in IDDM (e.g., DR3, DR4, and DQw8) produce products that have low affinity for the tolerogenic peptide or peptides or that bind the peptide or peptides in the wrong orientation or configuration for establishing tolerance. I also discuss the multiplicity of HLA loci, alleles, and amino acids contributing to IDDM and the fact that the associations of specific loci, alleles, and even genotypes with IDDM depend not only on their intrinsic properties but also on various population parameters. PMID- 1733801 TI - Influence of STZ-induced diabetes on zero-stress states of rat pulmonary and systemic arteries. AB - Zero-stress states of the main pulmonary arteries and aorta and small systemic arteries were determined in 22 nondiabetic and 29 streptozocin (STZ)-induced diabetic rats. The zero-stress state of each vessel was obtained by cutting the vessel transversely into a series of short rings, then cutting each ring radially, which caused the ring to spring open into a sector. Each sector can be characterized by its opening angle. The opening angle has strong regional dependence. In some regions of rat arteries, the opening angle can be greater than 360 degrees. Rats were studied 5, 10, 20, 30, and 40 days after an injection of 75 mg/kg body wt i.v. STZ. During diabetes development, the opening angles in general increased and reached a plateau in approximately 30 days. The maximum change of opening angle over normal lies in the range of 18-105 degrees, depending on location. The pulmonary arteries were affected by diabetes as much as the systemic arteries. The course of change of the opening angle during diabetogenesis was different from those of the serum glucose level and blood pressure. Blood pressure in carotid, external iliac, and pulmonary arteries did not change significantly in diabetogenesis. To clarify the physiological meaning of the opening angle, we measured the circumferential strain in the blood vessel wall in homeostatic condition and the residual strain at the no-load state, with both strains referred to the zero-stress state. We calculated the corresponding stresses in the vessel wall. The circumferential stress in the vessel wall was greatly increased by diabetes; great errors will result if the opening angle is ignored. PMID- 1733802 TI - Effects of streptozocin-induced diabetes and food restriction on quantities and source of T4 and T3 in rat tissues. AB - Diabetes mellitus and fasting are both associated with low plasma thyroid hormone concentrations and loss of body weight. To discriminate between the separate effects of energy shortage and insulin, we studied control rats, diabetic rats (DM), DM rats treated with insulin (DMI), and rats after modified fasting (MF1 and MF2; 70 and 30% of normal daily food intake, respectively). In double isotopic equilibrium experiments, we determined the tissue thyroxine (T4) and triiodothyronine (T3) concentrations and the contribution of local T4-to-T3 conversion to total T3 in rat tissues; thyroidal T4 and T3 secretion and extrathyroidal T3 production were calculated. In DM and DMI rats, plasma T4 and T3 decreased; in MF1 and MF2 rats, only plasma T4 decreased. Thyroidal T4 secretion decreased, whereas that of T3 remained normal. The decrease in tissue T4 in MF and DM rats paralleled the decrease in plasma T4. Although plasma T3 did not differ in DM and DMI rats, total T3 concentrations in all tissues were not the same due to changed uptake of T3 from plasma and local T4-to-T3 conversion; these changes were not found in several tissues of MF1 and MF2 rats. Our results suggest that the decrease in tissue T4 during diabetes mellitus is due to the decrease in plasma T4 caused by the decreased thyroidal secretion, possibly due to intracellular energy shortage. The changes in tissue T3 during diabetes mellitus are only partly attributable to the same phenomenon; in several tissues, the decrease in T3 seems more related to the lack of insulin. PMID- 1733803 TI - Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects. AB - Pentosidine is a fluorescent advanced Maillard/glycosylation product and protein cross-link present in elevated amounts in skin from diabetic and uremic subjects. A high-performance liquid chromatographic (HPLC) assay was developed to quantitate pentosidine in plasma and erythrocytes and other tissue proteins with low levels of pentosidine. High protein content and presence of basic amino acids and O2 during acid hydrolysis led to the formation of fluorescent artifacts that could be separated from true pentosidine through combined reverse-phase ion exchange HPLC. No true pentosidine was formed during acid hydrolysis of ribated protein, suggesting that Amadori products do not generate artifactual pentosidine during hydrolysis. With the combined reverse-phase ion-exchange chromatographic assay, we found a 2.5-fold (P less than 0.001) and a 23-fold (P less than 0.001) elevation of mean +/- SD plasma protein pentosidine in diabetic (2.4 +/- 1.2 pmol/mg) and uremic (21.5 +/- 10.8 pmol/mg) subjects compared with healthy (0.95 +/- 0.33 pmol/mg) subjects. Pentosidine in hemolysate was normal in diabetes but dramatically elevated in uremia (0.6 +/- 0.4 pmol/mg hemoglobin, P less than 0.001). Although the precise nature of the pentosidine precursor sugar is unknown, plasma pentosidine may be a useful marker for monitoring the biochemical efficacy of trials with aminoguanidine or other treatment modalities. Furthermore, pentosidine in plasma proteins may act as a signal for advanced glycosylation end product-mediated receptor uptake by macrophages and other cells and contribute to accelerated atherosclerosis in diabetes and uremia. PMID- 1733804 TI - Alterations in cardiac parasympathetic indices in STZ-induced diabetic rats. AB - Autonomic neuropathy involving parasympathetic innervation is a complication of diabetes mellitus. Biochemical and morphological indices of the parasympathetic innervation of the heart were investigated in rats after diabetes mellitus was induced with streptozocin (STZ). Choline acetyltransferase (CAT) activity was used as a biochemical marker for parasympathetic innervation. Total CAT activity within the hearts of diabetic rats was unchanged after 1 and 2 wk of diabetes and was significantly reduced after 4, 8, and 12 wk. Morphological changes within the cardiac portion of the parasympathetic innervation were assessed at 8 wk when CAT activity was decreased. In diabetic rats, there was a reduction in both cardiac ganglion cell size and number. In contrast, in insulin-treated STZ-induced diabetic rats, ganglion cells were similar in size and number to those in a control group given 3-O-methylglucose to prevent induction of diabetes mellitus by STZ. Thus, diabetes mellitus is associated with alterations in cardiac parasympathetic innervation in rats, and supplemental insulin protects against these changes. These alterations may contribute to impaired parasympathetic neural control of the heart in diabetes mellitus. PMID- 1733805 TI - Effect of vitamin C on glycosylation of proteins. AB - Twelve nondiabetic subjects consumed 1 g/day vitamin C for 3 mo. A fasting blood sample was taken at the start of the study and at the end of each month for the measurement of plasma and intraerythrocyte glucose, vitamin C, glycosylated hemoglobin (affinity chromatography and electrophoresis), and glycosylated albumin (affinity chromatography). Although there were no significant changes in fasting glycemia, glycosylated hemoglobin (affinity chromatography) decreased 18%, from 6.18 +/- 0.48% (mean +/- SD) at the start to 5.05 +/- 0.50% (P less than 0.0001) after 3 mo, whereas, HbA1 measured by electrophoresis increased 16%, from 6.17 +/- 0.61 to 7.16 +/- 0.59% (P less than 0.0001) in this period. Glycosylated albumin decreased 33%, from 1.56 +/- 0.24 to 1.04 +/- 1.01% (P less than 0.0001) after 3 mo. This discrepancy between glycosylated hemoglobin measured by electrophoresis and affinity chromatography was due to methodological differences between the two techniques, with affinity chromatography measuring "true" glycosylated hemoglobin. The greater decrease found with glycosylated albumin was probably due to the different distribution of vitamin C between plasma and within the erythrocyte, levels after 1 mo of supplementation being 109 +/- 19 and 59 +/- 9 microM, respectively (P less than 0.001). This indicates that administration of oral vitamin C may inhibit the glycosylation of proteins in vivo by a competitive mechanism. PMID- 1733806 TI - Effect of acute hyperglycemia on glucose metabolism in skeletal muscles in IDDM patients. AB - The effect of acute hyperglycemia on glucose metabolism in skeletal muscles was assessed during replacement insulin infusion in 11 patients with insulin dependent diabetes mellitus (IDDM). With a primed continuous [3-3H]glucose infusion and indirect calorimetry, glucose metabolism was assessed during a basal period (plasma glucose [PG] 5 mM) and during a hyperglycemic period (4-h i.v. glucose infusion, PG 12.1 mM). Biopsies were taken from the vastus lateralis muscle during both periods. On a control day, glucose metabolism was assessed in 10 patients during a basal period (PG 5.2 mM) and after 4 h with no glucose infusion (PG 4.2 mM). Nonoxidative glucose disposal increased during hyperglycemia (32 +/- 7 vs. 51 +/- 9 mg.m-2.min-1, P less than 0.05), whereas glucose oxidation remained constant. On the control day, nonoxidative glucose disposal decreased from the basal to the second (control) period (33 +/- 7 vs. 22 +/- 6 mg.m-2.min-1, P less than 0.05), and glucose oxidation remained constant. The activity of glycogen synthase in muscle biopsies (fractional velocities [0.1 and 10 mM glucose 6-phosphate (G6P)]) decreased slightly during hyperglycemia (18 +/- 2 vs. 12 +/- 2%, P less than 0.05) and on the control day (26 +/- 4 vs. 20 +/ 3%, P less than 0.05). Hyperglycemia increased the intracellular concentration of free glucose, corrected for estimated extracellular glucose (0.56 +/- 0.11 vs. 1.43 +/- 0.19 mM, P less than 0.01), G6P (0.14 +/- 0.04 vs. 0.23 +/- 0.08 mM, P less than 0.02), and lactate (2.88 +/- 0.33 vs. 4.46 +/- 0.61 mM, P less than 0.05), whereas these substrate concentrations remained constant on the control day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733807 TI - Cloning and expression of IDDM-specific human autoantigens. AB - A DNA cloning approach was taken to identify islet cell protein antigens that are recognized specifically by insulin-dependent diabetes mellitus (IDDM) sera. A human islet cDNA library was generated and screened with diabetic sera. In this article, identification of two clones is described. Proteins expressed by these lambda phages appeared to react specifically with newly diagnosed diabetic sera. Islet cell antibody 12 (ICA12) was tested by Western blotting. ICA512 was not reactive with sera in the Western format but was specifically immunoprecipitated by diabetic sera from an Escherichia coli extract. PMID- 1733808 TI - Glucose transporter levels in tissues of spontaneously diabetic Zucker fa/fa rat (ZDF/drt) and viable yellow mouse (Avy/a). AB - We used antibodies to the fat/muscle glucose transporter (GLUT4) and the liver glucose transporter (GLUT2) to measure levels of these proteins in various tissues of two rodent models of non-insulin-dependent (type II) diabetes mellitus: the obese spontaneously diabetic male Zucker fa/fa rat (ZDF/drt) and the male viable yellow Avy/a obese diabetic mouse. The ZDF/drt strain generally develops overt diabetes associated with decreased plasma insulin levels. Depending on the age of the animals, the ZDF/drt rats can be arbitrarily segregated into age-matched obese, mildly diabetic (blood glucose less than 11 mM) and obese, and severely diabetic (blood glucose greater than 20 mM) groups. Avy/a mice are comparably hyperglycemic but unlike the ZDF/drt rats are severely hyperinsulinemic. In both groups of diabetic animals, GLUT4 in adipose tissue, heart, and skeletal muscle was reduced 25-55%, and GLUT2 in liver was increased 30-40%, relative to lean, age-matched controls. However, when the mildly diabetic ZDF/drt rats were compared to the lean controls, the only significant difference was a 25% reduction of GLUT4 in heart. Within all of the ZDF/drt rats (excluding the lean controls), GLUT2 in liver and GLUT4 in adipose tissue, heart, and skeletal muscle correlated significantly with glycemia. These data suggest that, in these two models of type II diabetes, glucose transporter levels in muscle, adipose tissue, and liver are regulated in a tissue-selective manner in response to changes in insulin and glucose. Furthermore, at least in the ZDF/drt rat, alterations in GLUT2 and/or GLUT4 protein levels appear not to be associated with obesity per se but appear to be secondary to the severely diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733809 TI - Insulin stimulates accumulation and efflux of macromolecules in isolated nuclei from H35 hepatoma cells. AB - This study used 10-nm gold particles with 5-7 insulin molecules attached (Au10 Ins) to investigate the site of interaction of insulin with the nuclear envelope during insulin uptake into intact isolated nuclei. Despite its size, and in the absence of ATP, Au10-Ins entered nuclei through the nuclear pore and associated with the heterochromatin. Because Au10-Ins is essentially gold-bovine serum albumin (Au-BSA) with a few insulin molecules attached, the effect of insulin and other growth factors on the nuclear accumulation of BSA coupled to 10-, 15-, and 24-nm-diam colloidal gold particles (Au10-BSA, Au15-BSA, and Au24-BSA) was determined. The Au-BSA complexes were excluded from nuclei in the absence of insulin. Insulin (0.5-100 ng/ml) caused a dose-dependent accumulation of Au10-BSA in the nucleus. The nuclear membrane was shown to be intact by several criteria, therefore, accumulation of Au-BSA occurred via the nuclear pore and was not due to leakage across or through the membrane. Uptake of 15- and 24-nm Au-BSA molecules was not affected by insulin, suggesting the hormone had a limited effect in increasing the functional diameter of the nuclear pores. Glucagon, epidermal growth factor, platelet-derived growth factor, insulinlike growth factor I, and insulin A or B chains did not stimulate the accumulation of Au10 BSA. The insulin-stimulated accumulation of Au10-BSA was blocked by concanavalin A, mimicked by wheat-germ agglutinin, and did not require ATP. The Au10-BSA in the nucleus was associated with heterochromatin, suggesting it bound to a nuclear element.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733810 TI - Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study. AB - We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbA1c remained significantly related to CVD among women. The relative odds of CVD increased 1.39 fold (95% confidence interval 1.06-1.83) for increases in HbA1c of 1% (e.g., for HbA1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking beta-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between "casual" blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA1c, and CVD among older women. PMID- 1733811 TI - Exaggerated sensitivity to NE-induced vasoconstriction in IDDM patients with microalbuminuria. Possible etiology and diagnostic implications. AB - Increased urinary albumin excretion rate (AER) in the microalbuminuric phase of diabetic nephropathy has been attributed to intraglomerular hypertension. This could be caused by constriction of efferent glomerular arterioles, which carry alpha-adrenoceptors. We tested the hypothesis that insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria are hypersensitive to vasoconstriction induced by norepinephrine (NE). We studied 15 IDDM patients with microalbuminuria (AER 32-295 mg/24 h), 13 IDDM patients with normal AER (5-24 mg/24 h), and 9 nondiabetic subjects (AER 8-22 mg/24 h). All were normotensive. NE-induced vasoconstriction was measured in dorsal hand veins, which carry alpha receptors similar to those of glomerular efferent arterioles. Vein diameter was measured with a linear displacement probe during a stepped NE infusion (1-32 ng/min) into the vein, and venoconstriction was expressed as a percentage of the maximum passively distended venous diameter. Microalbuminuric IDDM patients exhibited significantly greater vasoconstriction (P less than 0.005) at all NE infusion rates than both other groups. The NE infusion rate producing 50% of maximal venoconstriction (ED50) in the microalbuminuric IDDM group (median 1.1 ng/min, range 0.2-25.2 ng/min) was significantly less than in both the normoalbuminuric IDDM group (median 12.5 ng/min, range 4.9-40.5 ng/min, P = 0.00007) and the nondiabetic group (median 17.7 ng/min, range 5.9-42.2 ng/min, P = 0.0003). Dose-response curves and ED50 did not differ significantly between normalbuminuric IDDM and nondiabetic groups. IDDM patients with microalbuminuria are hypersensitive to NE-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733812 TI - Subcellular localization of GLUT4 in nonstimulated and insulin-stimulated soleus muscle of rat. AB - Soleus muscles of fed rats were fixed by vascular perfusion with paraformaldehyde; individual fibers were teased and immunostained with a polyclonal antibody against the COOH-terminal of GLUT4. The binding sites were visualized by a horseradish peroxidase-coupled secondary antibody and diaminobenzidine. The fibers were embedded in epoxy resin and studied by electron microscopy. Strong immunoreactivity was found in subsarcolemmal clusters of vesicles and cisternae, Golgilike structures, and triadic junctions. Clusters of vesicles between myofibrils were occasionally stained. The plasma membrane was unlabeled. However, the plasma membrane was labeled when the rats had been injected with insulin (40 U/kg body wt) 15 min before perfusion fixation. In non insulin-injected rats, the plasma membrane might show spotty staining close to clusters of intensely labeled subsarcolemmal vesicles. This may have been due to diffusion but may also indicate that there are domains of GLUT4 in the plasma membrane of nonstimulated fibers or that the endogenous insulin activity to some extent had translocated GLUT4 from the intracellular pool into the plasma membrane. Coated vesicles that were also labeled were found adjacent to subsarcolemmal vesicles and cisternae; it is possible that coated vesicles play a role during insulin- or contraction-induced translocation of GLUT4 between subsarcolemmal pool and plasma membrane. It has been proposed that glucose uptake into skeletal muscle fibers takes place across the t-tubule membrane rather than across the plasma membrane. This would explain the presence of GLUT4 at triadic junctions. Alternatively, we suggest that GLUT4 in t-tubules represents a second intracellular pool. PMID- 1733813 TI - Tissue-specific regulation of basic fibroblast growth factor mRNA levels by diabetes. AB - Because basic fibroblast growth factor (bFGF) is recognized as an angiogenic factor and diabetes is characterized by multiple vascular complications, including diabetic microangiopathy, we examined the regulation of tissue bFGF mRNA levels by diabetes. Diabetes was induced in male Sprague-Dawley rats by injection of 125 mg/kg body wt i.v. streptozocin (STZ), with intensive insulin therapy initiated in half of the diabetic rats. Rats were killed 96 h postinjection of STZ. Tissue bFGF and insulinlike growth factor I (IGF-I) mRNA levels were measured simultaneously with a solution hybridization-RNase protection assay. bFGF mRNA levels increased from 1.7- to 2.7-fold in eye, heart, lung, and brain from diabetic compared with buffer-injected control rats. In skeletal muscle, bFGF mRNA levels decreased to 23% of control levels, whereas bFGF mRNA levels were unchanged in kidneys from diabetic versus control rats. Changes in tissue bFGF mRNA levels were partially reversed by insulin treatment in all tissues. In contrast, IGF-I mRNA levels were significantly decreased from 15 to 50% of control levels in all tissues studied except those in brain, which decreased to only 85% of control levels. These data demonstrate that bFGF mRNA levels are altered by diabetes in a tissue-specific fashion and are consistent with the hypothesis that increased production of bFGF may contribute to the development of diabetic microangiopathy in some tissues. PMID- 1733814 TI - Insulin-stimulated glucose transport in circulating mononuclear cells from nondiabetic and IDDM subjects. AB - The objectives of this study were 1) to evaluate glucose transport and its regulation by insulin in easily accessible human cells, 2) to investigate the glucose transporter isoforms involved, and 3) to establish whether a defect in glucose transport is associated with peripheral insulin resistance, which is common in insulin-dependent diabetes mellitus (IDDM) patients. We measured 2 deoxyglucose (2-DG) uptake in circulating mononuclear cells from 23 nondiabetic adults, 16 adults with IDDM, and 10 children with IDDM. Circulating mononuclear cells were separated from whole blood by Ficoll gradients and incubated with +/- 1 nM insulin. 2-DG uptake was measured after incubation with [3H]2-DG and cell separation through corn oil-phthalate. Cytochalasin B-inhibitable 2-DG uptake (basal and insulin stimulated) was higher in control than in IDDM subjects (P less than 0.001). Insulin significantly increased 2-DG uptake or 3-O methylglucose uptake in both groups. Basal and insulin-stimulated 2-DG uptake was similar for adults and children with IDDM and did not correlate with age or body mass index in any group or disease duration, insulin dosage, or HbA1c in IDDM. In separated monocytes and lymphocytes, 2-DG uptake increased in response to insulin only in the monocyte population. Insulin dose-response curves indicated maximal stimulation of hexose uptake at 1-2 nM insulin for both control and diabetic subjects and demonstrated a significant decrease in maximal insulin response in the latter. Immunoblotting with specific antibodies revealed that circulating mononuclear cells and separated monocytes express the GLUT1 but not the GLUT4 isoform of the glucose transporter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733815 TI - Duration of obesity increases the incidence of NIDDM. AB - The effect of duration of obesity on incidence of non-insulin-dependent diabetes mellitus (NIDDM) was determined among Pima Indians. Duration of obesity was defined as the time since body mass index (BMI) was first known to be at least 30 kg/m2. Among 1057 participants eligible for study, there were 224 incident cases of NIDDM in 5975 person-yr of follow-up. The association of duration of obesity with incidence of diabetes adjusted for age, sex, and current BMI was highly significant (P less than 0.0001). This adjusted incidence of diabetes in cases/1000 person-yr of obesity was 24.8 for people with less less than 5 yr of obesity, 35.2 for people with 5-10 yr of obesity, and 59.8 for people with at least 10 yr of obesity. There was no apparent excess risk of diabetes for people who had a BMI of at least 30 kg/m2 and then lost weight. They had a slightly nonsignificantly higher rate than people who had not attained a BMI of at least 30 kg/m2 and a lower rate than people whose BMI remained 30-35 kg/m2. The relationship of duration of obesity with serum insulin concentrations among nondiabetic people was determined controlling for sex and age, BMI, and plasma glucose concentrations at the time of a glucose tolerance test. Duration of obesity was inversely associated with fasting serum insulin concentration through most of the range of fasting plasma glucose concentrations (P less than 0.001) and tended to be inversely associated with 2-h postload serum insulin concentration through the entire range of postload plasma glucose concentrations (P = 0.058). PMID- 1733816 TI - Dose-response relationship between lymph insulin and glucose uptake reveals enhanced insulin sensitivity of peripheral tissues. AB - To examine the role of transcapillary insulin transport to peripheral insulin sensitivity in vivo, we performed dose-response experiments in which both plasma and thoracic duct lymph insulin and glucose utilization (Rd) were measured in conscious dogs. Euglycemic clamps (n = 22) consisted of a 3-h activation period in which insulin was infused (rates: "physiological" 3.6, 5.4, 7.2 pmol.min-1.kg 1; "pharmacological" 108 pmol.min-1.kg-1), followed by a 3-h deactivation period. [14C]inulin was also infused as a diffusionary marker. Insulin sensitivity was estimated as the ED50. When based on plasma insulin, ED50 was 480 pM. However, when calculated from lymph (i.e., interstitial) insulin measurements, ED50 was 240 pM. Thus, interstitial insulin measurements reveal that insulin sensitivity of peripheral tissues is approximately twice that estimated from plasma insulin and is similar to sensitivity reported for suppression of hepatic glucose production. Furthermore, although [14C]inulin achieved equilibrium between plasma and lymph within 180 min, within the physiological range, steady state plasma insulin was higher than insulin in lymph (306 +/- 18, 474 +/- 42, and 780 +/- 60 pM vs. 180 +/- 18, 318 +/- 12, and 504 +/- 36 pM; P less than 0.0001); plasma insulin achieved steady state faster than lymph insulin (6 +/- 1, 6 +/- 2, and 11 +/- 3 min vs. 29 +/- 4, 16 +/- 6, and 44 +/- 8 min; P less than 0.01) and disappeared faster (5 +/- 2, 7 +/- 2, and 15 +/- 6 min vs. 37 +/- 8, 32 +/- 4, and 43 +/- 9 min; P less than 0.01). The time course of lymph insulin at each dose was similar to that of Rd, and at each dose, unlike plasma insulin, lymph insulin was strongly correlated with Rd (r = 0.93 or better). At pharmacological hyperinsulinemia (plasma 35232 +/- 5250 pM, lymph 27366 +/- 4380 pM), Rd rose faster than lymph insulin and disappeared more slowly than insulin. Thus, lymph insulin data indicate that the periphery is more sensitive to insulin than previously realized from estimates based solely on plasma hormone. Furthermore, lymph insulin is proportional to Rd within the physiological but not pharmacological range of insulin, indicating that transcapillary insulin transport is rate limiting for insulin action in this range. Finally, based on in vivo lymph (i.e., interstitial) insulin measurements, peripheral tissue is almost twice as sensitive to insulin than previously realized. PMID- 1733817 TI - Visually impaired children's visual characteristics and intelligence. AB - The results are presented of the mentally normal, visually impaired, Braille educated population of Dutch and Dutch-speaking Belgian children on verbal and non-verbal tests of intelligence and school achievement. The children were aged between six and 15 years old. Their visual characteristics were strongly inter related and correlated similarly with the test scores. Colour perception did not contribute to the intelligence test score variation after controlling for near visual acuity. Congenital blindness had a positive influence on verbal memory and a negative influence on spatial ability. PMID- 1733818 TI - Herpes simplex virus encephalitis: problems in diagnosis. AB - Six children aged 13 days to nine years with herpes simplex encephalitis (HSE) are presented. Institution of appropriate antiviral treatment was later than six days in three cases; original diagnosis in these cases were post-traumatic epilepsy, bacterial meningitis and febrile convulsion. Initially pyrexia was absent in two cases and cranial CT was normal in two cases. Encephalitic changes were observed on the EEGs of five children. Diagnosis was confirmed by paired serological titres, brain biopsy, vesicle culture and CSF titres. The outcome for all six children was poor. HSE should always be considered in children presenting with focal seizures, even when apyrexial and with normal CT findings. In such situations, saving CSF for antibody titres or antigen identification should be routine practice. Treatment with acyclovir is justified before precise virological diagnosis has been established. PMID- 1733819 TI - Oral-motor dysfunction and feeding disorders of infants with Turner syndrome. AB - The oral-motor function of 10 infants with Turner syndrome and their age- and sex matched controls were assessed during feeding. In addition to well-recognised dysmorphic features, including oral anomalies and high-arched palates, index infants had marked hypotonia of the cheeks and lips, dysfunctional tongue movements and poorly developed chewing skills. Their meal-times were significantly shorter than those of the controls and they weighed significantly less at six, 12 and 15 months. All mothers of infants with Turner syndrome complained of difficulties feeding their children and these problems often had been present since birth. PMID- 1733820 TI - Isosorbide in the medical management of hydrocephalus in children with myelodysplasia. AB - Fourteen children with hydrocephalus associated with myelodysplasia were given isosorbide (8 to 12 g/kg/day) and compared with 17 children managed without it. Three of the treated and three of the untreated children did not require shunting. The mean interval between back closure and shunt placement was 33 days for the controls and 115 days for the treated children. Two of the treated children developed gastro-intestinal symptoms that necessitated withdrawal of the isosorbide. Although isosorbide did extend the interval between back closure and shunt placement, its side-effects and the availability of alternative treatments render it unsuitable for the management of hydrocephalus in children with myelodysplasia. PMID- 1733821 TI - The effect of pethidine on the neonatal EEG. AB - Thirty-two preterm infants were monitored with an on-line cotside EEG system for periods of up to nine days. Changes in the normal pattern of discontinuity of the EEG were seen in association with pethidine administration. The duration of the EEG suppression after pethidine administration was greatest after the first dose and progressively less with subsequent doses. It was not related to the gestational maturity or postnatal age at which the dose was given. This system of EEG analysis allowed recognition of this previously undescribed effect of pethidine on the neonatal EEG, and should have application to monitoring the effects of brain function of other drugs in routine neonatal practice. PMID- 1733822 TI - Positional asphyxia in individuals with severe cerebral palsy. AB - The authors report the accidental death by positional asphyxia of three individuals with cerebral palsy occurring after they had been placed in bed for the night. During the five-year period between 1984 and 1989, 12 per cent of deaths from positional asphyxia in King County, Washington, involved individuals with cerebral palsy. Such accidents are similar to those occurring among healthy young children, perhaps because both groups have limited motor skills. Further research into accidents among disabled persons may clarify their special risks and possibly lead to modifications in bed design. PMID- 1733823 TI - Chiari malformation type I in a child with velopharyngeal insufficiency. AB - A five-year-old girl was referred for chronic and stable velopharyngeal insufficiency. Pharyngoplasty was performed, without significant improvement, and further neurological investigation was undertaken. Clinical examination and electromyography led to a suspicion of denervation of the IX, X and XI cranial nerves. Magnetic resonance imaging revealed a type 1 Chiari malformation. PMID- 1733824 TI - Holoprosencephaly with retroprosencephalic extracerebral cyst. AB - The authors report holoprosencephaly combined with an enormous extracerebral glio ependymal cyst in the superior cistern of a 10-week-old boy. The cyst had compressed the holosphere at the floor of the anterior fossa and had caused herniation of the cerebellar vermis and tonsils at the foramen magnum, along with ascending cervical roots. This uncommon combination of lesions clinically may mimic hydranencephaly or hydrocephalus. PMID- 1733825 TI - Carrier detection and prenatal diagnosis of alpha-thalassemia of Southeast Asian deletion by polymerase chain reaction. AB - Alpha-thalassemia of Southeast Asian deletion (-- SEA/) is very common in Southeast Asia. Homozygosity of this genotype is the major cause of Hb Bart's hydrops fetalis in Taiwan. With polymerase chain reaction using three oligonucleotide primers bridging the common deletion breakpoint, a DNA fragment of 194 basepairs (bp) was amplified in chromosomes with the -- SEA determinant and a DNA fragment of 287 bp was amplified in chromosomes without this deletion. In our pilot study including 8 normal subjects, 20 obligate carriers, and 11 homozygotes of the deletion, all the genotypes were determined and then confirmed by Southern blotting and DNA hybridization with phi zeta globin gene probe. For prenatal diagnosis, 55 at-risk pregnancies were collected. Chorionic villus sampling was done in 51 cases and early amniocentesis was done in 4 cases. Fourteen cases (25.5%) were diagnosed as normal, 25 (45.5%) as heterozygotes, and 16 (29%) as homozygotes of -- SEA. All of the diagnoses were also confirmed as aforementioned. With polymerase chain reaction, the determination of the -- SEA deletion is straightforward and is much quicker and easier than with conventional Southern blotting and DNA hybridization. In areas with a high prevalence of -- SEA deletion, this method provides a rapid tool for carrier detection and prenatal diagnosis. PMID- 1733826 TI - Parental origin and germline mosaicism of deletions and duplications of the dystrophin gene: a European study. AB - Knowledge about the parental origin of new mutations and the occurrence of germline mosaicism is important for estimating recurrence risks in Duchenne (DMD) and Becker muscular dystrophy (BMD). However, there are problems in resolving these issues partly because not all mutations can as yet be directly detected, and additionally because genetic ratios are very sensitive to ascertainment bias. In the present study, therefore, analysis was restricted to currently detectable mutations (deletions and duplications) in particular types of families which tend to be rare. In order to obtain sufficient data we pooled results from 25 European centers. In mothers of affected patients who were the first in their family with a dystrophin gene deletion or duplication, the ratio between the paternal and the maternal origin of this new mutation was 32:49 (binomial test P = 0.075) for DMD. In five BMD families the ratio between paternal and maternal origin of new mutations was 3:2. Recurrence risk because of maternal germline mosaicism was studied in sisters or subsequent sibs of isolated cases with an apparently new detectable mutation. In 12 out of 59 (0.20; 95% CI 0.10-0.31) transmissions of the risk haplotype the DMD mutation was transmitted as well. No recurrences were found in nine BMD families. PMID- 1733827 TI - Birth and population prevalence of Duchenne muscular dystrophy in The Netherlands. AB - Mutations causing Duchenne muscular dystrophy (DMD) have a short survival. Therefore, birth and population prevalence are maintained by new mutations. The present inventory was made to estimate the birth and population prevalence rates of DMD in the Netherlands. Seven methods of case identification were used. Data on 496 definite, probable or possible DMD patients born since 1961, or alive on January 1, 1983, were obtained. Several methods gave an estimated ascertainment of more than 95%. The prevalence rate at birth of DMD was estimated at 23.7 x 10( 5) (1:4215) male live births (MLB) yearly. The prevalence rate in the male population on January 1, 1983 was 5.4 x 10(-5) (1:18496). About 1% of the males in this study may have autosomal recessive Duchenne-like muscular dystrophy. Until now there has been no convincing evidence for geographic differences in DMD prevalence at birth. A list of frequency studies of Duchenne muscular dystrophy is included. The DMD mutation rate calculated by the indirect method is 7.9 x 10( 5) genes per generation. However, this may well be an over-estimate, as this method does not account for germline mosaicism. Using a modified sex ratio method the proportion of sporadic DMD among all cases was estimated to be 0.106 (range 0 0.332). High frequency of germline mosaicism in DMD is a likely cause for the apparent lack of sporadic cases as found in previous studies, if mutation rates in male and female gametes are equal. Therefore, methods for estimating the proportion of new mutants in DMD should take germline mosaicism into account. The modified sex ratio method allows incorporation of data on germline mosaicism if available. PMID- 1733828 TI - Heterozygote deficiency, population substructure and their implications in DNA fingerprinting. AB - Substructured populations exhibit an overall deficiency of heterozygosity whose proportional magnitude depends on the nature of substructuring, i.e., the number of subpopulations (s), their time of divergence (t) from the ancestral population, and the rate of gene flow amongst them (m). Since apparent heterozygote deficiency could be caused by many factors other than population substructuring, one must examine the nature of substructuring that could produce the observed extent of heterozygote deficiency, in order to infer the substructuring from an observed heterozygote deficiency. Using the equivalence of proportional heterozygote deficiency and the coefficient of gene differentiation (GST), we can generate isolines of GST as functions of s, t (in units of 2Ne generations, Ne being the effective population size) and m. Analytical results suggest that large GST values cannot be reached by substructuring alone, unless the number of subpopulations are large and they remain isolated over a long period of time. Application of the theory to population data on six variable number of tandem repeats (VNTR) loci in US Caucasians and US Blacks demonstrates that the observed heterozygote deficiencies at these loci cannot be explained by substructuring within these populations alone. This is so because such large values of GST (3%-10%) would require an absence of gene exchange between the subpopulations and a divergence time from each other of at least 25,000 years ago, neither of which is compatible with the demography and ethnohistory of US Caucasians and Blacks. In contrast, the inability to detect extreme-sized alleles and/or incomplete resolution of nearly similar-sized alleles following Southern gel electrophoresis could easily explain the observed heterozygote deficiencies. The implications of these results are discussed in the context of the forensic use of DNA-typing data, and justify the employment of population genetic principles in forensic genetics. PMID- 1733829 TI - Ewing's tumor X mouse hybrids expressing the MIC2 antigen: analyses using fluorescence CDD-banding and non-isotopic ISH. AB - We present a highly sensitive method that has been applied to map the chromosomal origin of the prominent cell surface antigen of Ewing's tumor cells recognized by monoclonal antibody HBA-71. The technique allows an unambiguous identification of human chromosomal material in interspecific cell hybrids. This is achieved by fluorescent in situ hybridization of biotinylated total human DNA, followed by high resolution fluorescence banding with the chromomycin/distamycin/DAPI triple stain. An advantage of this method is that all signals can be visualized in one single operation by simply switching the appropriate filter blocks. The protocol has proved extremely useful in gene mapping by means of interspecific cell hybrids, a technique that depends on the accurate and unambiguous recognition of the relevant (e.g., human) genetic material in the clonal genome. Our studies confirm that this antigen is the product of the MIC2 gene, which is so far the only well-studied pseudoautosomal gene in man, and which is located on the short arms of chromosomes X and Y. Furthermore, no influence of the Ewing's tumor specific translocation t(11;22) on MIC2 expression could be discerned. PMID- 1733830 TI - Mosaicism in 45,X Turner syndrome: does survival in early pregnancy depend on the presence of two sex chromosomes? AB - Cytogenetic and molecular genetic findings in 91 patients with Turner syndrome are reported. In 87 patients, chromosome studies were carried out both in lymphocyte and fibroblast cultures. Mosaicism was demonstrated in 58 of these patients (66.7%), whereas only 18 (20.7%) were apparent non-mosaic 45,X, and 11 patients (12.6%) showed non-mosaic structural aberrations of the X chromosome. Among the mosaic cases 16 (18.4% of all patients) displayed a second cell line containing small marker chromosomes. The association of Y-specific chromosomal material with the presence of marker chromosomes was demonstrated in 6 out of 7 mixoploid fibroblast cell lines by polymerase chain reaction amplification and by Southern-blot analysis. The observation of ring formation and morphological variability in vivo and in vitro, and the continuous reduction in the percentage of cells containing marker chromosomes in longterm cultivation experiments indicated an increased instability of marker chromosomes. The findings suggest that in vivo selection of structurally altered sex chromosomes exists. Thus, the observation of apparent non-mosaic 45,X chromosomal complements in liveborn individuals with Turner syndrome does not contradict the hypothesis that some degree of mosaicism is necessary for survival in early pregnancy. PMID- 1733831 TI - Chromosomal localization of the human glycoasparaginase gene to 4q32-q33. AB - Glycoasparaginase cleaves the N-glycosidic linkage between asparagine and N acetylglucosamine in the degradation of glycoproteins. In humans, a deficient activity of glycoasparaginase results in accumulation of glycoasparagines, causing the lysosomal storage disease aspartylglycosaminuria. Recombinant plasmid containing the cDNA insert encoding human glycoasparaginase was used to localize the enzyme to chromosome 4q32-q33 by in situ hybridization to metaphase chromosomes prepared from normal human lymphocytes. PMID- 1733832 TI - Exclusion map of Salla disease: attempts to localize the disease gene using a computer program. AB - Salla disease is a lysosomal storage disorder due to impaired transport of free sialic acid across the lysosomal membrane. The clinical presentation of this autosomal recessive trait is severe psychomotor retardation from early infancy on. In order to determine the gene locus for the disease we have initiated a genetic linkage study using polymorphic gene markers in representative family material comprising about 60% of all families known to be affected with Salla disease. Here we present an exclusion map based on combined linkage data from 64 informative loci on 19 autosomes. Theoretically, at least 55% of the genome has been excluded as a locus for the disease gene, while some chromosome areas, particularly the long arm of chromosome 2, are highlighted as possible sites for the gene locus. PMID- 1733833 TI - Apolipoprotein E phenotypes and hyperlipidemia in patients under maintenance hemodialysis. AB - Apolipoprotein E phenotypes and gene frequencies were determined in 560 patients receiving long-term hemodialysis. In addition, fasting plasma lipid- and apolipoprotein-concentrations were evaluated in 245 of these individuals. The distribution of the three major apolipoprotein E alleles (epsilon 4, epsilon 3, and epsilon 2) and that of the six common apolipoprotein E phenotypes (E4/4, E3/3, E2/2, E4/2, E4/3, and E3/2) in the dialysis group was nearly identical to that of healthy controls. Patients with the apolipoprotein E phenotypes E2/2, E4/4 and E4/3 (comprising 24% of the whole group) had higher mean plasma cholesterol- and triglyceride-concentrations than those with the apolipoprotein E phenotypes E3/3 and E3/2 (72% of the whole group). Thus, the genetic polymorphism of apolipoprotein E may contribute to the individual risk of accelerated atherosclerosis in patients under maintenance hemodialysis. PMID- 1733834 TI - Heterogeneity of mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria. AB - Congenital erythropoietic porphyria (CEP) or Gunther's disease is an inborn error of heme biosynthesis transmitted as an autosomal recessive trait and characterized by a profound deficiency of uroporphyrinogen III synthase (UROIIIS) activity. We have previously described two missense mutations in the UROIIIS gene, confirming that the primary defect responsible for CEP is a structural alteration of this gene. We have extended our work to 5 additional unrelated families. Two new point mutations, a deletion and an insertion have been found in the messenger RNA. Our study shows that a molecular heterogeneity of the mutations exists in Gunther's disease. One mutation (C73R), however, appears to be more frequent than the others. Finally, the different normal and mutated proteins have been expressed in Escherichia coli to determine the consequence of the mutations on the enzyme activity. PMID- 1733835 TI - A family with RP3 type of X-linked retinitis pigmentosa: an association with ciliary abnormalities. AB - The results of linkage analysis in a family with X-linked retinitis pigmentosa (XLRP) are presented. Probe M27B (DXS255), localized to Xp11.22, was only loosely linked to XLRP, whereas pHOC3 (OTC), in the more distal Xp21.1 region, was tightly linked. In this family, the conditional probability of an RP3 locus (in Xp21.1-p11.4) was found to be 0.978 compared with 0.021 for an RP2 locus (in Xp11.4-p11.2). Risk assessment showed that 2 out of 4 "at risk" females showing no clinical abnormality have a high probability of being genetic carriers of XLRP. Some affected males have recurrent respiratory infections as a result of a condition indistinguishable from the immotile cilia syndrome; indeed, there is an association between XLRP and susceptibility to respiratory infections in the majority of affected males. The possibility that previously observed ciliary abnormalities in XLRP patients might be associated specifically with an RP3 locus abnormality is discussed. PMID- 1733836 TI - Distribution of ADH2 and ALDH2 genotypes in different populations. AB - The distribution of the human liver alcohol dehydrogenase, ADH2, and aldehyde dehydrogenase, ALDH2, genotypes in 21 different populations comprising Mongoloids, Caucasoids, and Negroids was determined by hybridization of the amplified genomic DNA with allele-specific oligonucleotide probes. Whereas the frequency of the ADH1(2) allele was found to be relatively high in the Caucasoids, Mexican Mestizos, Brazilian Indios, Swedish Lapps, Papua New Guineans and Negroids, the frequency of the ADH2(2) gene was considerably higher in the Mongoloids and Australian Aborigines. The atypical ALDH2 gene (ALDH2(2)) was found to be extremely rare in Caucasoids, Negroids, Papua New Guineans, Australian Aborigines and Aurocanians (South Chile). In contrast, this mutant gene was found to be widely prevalent among the Mongoloids. Individuals possessing the abnormal ALDH2 gene show alcohol-related sensitivity responses (e.g. facial flushing), have the tendency not to be habitual drinkers, and apparently suffer less from alcoholism and alcohol-related liver disease. PMID- 1733837 TI - Molecular abnormality of a Japanese glucose-6-phosphate dehydrogenase variant (G6PD Tokyo) associated with hereditary non-spherocytic hemolytic anemia. AB - The entire coding sequence of a Japanese class 1 variant (G6PD Tokyo) was amplified by the polymerase chain reaction from genomic DNA. Nucleotide analysis by a direct sequencing technique revealed a unique nucleotide substitution (1246 G to A) in exon 10, which predicts a Glu to Lys substitution at the 416th amino acid. This is another member of a conspicuous mutation cluster surrounding the putative NADP-binding domain. PMID- 1733838 TI - Localisation of the gene for Norrie disease to between DXS7 and DXS426 on Xp. AB - A highly informative microsatellite marker, DXS426, which maps proximal to DXS7 in the interval Xp11.4-Xp11.23, has been used to refine further the localisation of the gene for Norrie disease (NDP). The results from a multiply informative crossover localize the NDP gene proximal to DXS7. In conjunction with information from 2 NDP patients who have a deletion for DXS7 but not for DSX426, our data indicate that the NDP gene lies between DXS7 and DXS426 on proximal Xp. PMID- 1733839 TI - Familial synovial chondromatosis combined with dwarfism. AB - In a family with synovial chondromatosis affecting at least three, presumably five members, the articular disorder was combined with dwarfism. The persons with joint disorders were below the third percentile in body height, but family members with normal articular function had normal height. We believe this to be the first description of a combination of synovial chondromatosis with genetically caused dwarfism. PMID- 1733840 TI - A possible example of gene conversion with a common beta-thalassemia mutation and Chi sequence present in the beta-globin gene. PMID- 1733841 TI - Germinal "mosaicism"--germline mutation or chimerism? PMID- 1733842 TI - Prader-Willi or Angelman syndrome in familial 15q11----q13 deletion of maternal origin? PMID- 1733843 TI - Triple trisomy in a spontaneous abortion. PMID- 1733844 TI - High population incidence of the 15p marker D15Z1 mapping to the short arm of one homologue 14. PMID- 1733845 TI - Chromosome 15p marker D15Z1 frequently maps to the short arm of other D-group chromosomes. PMID- 1733846 TI - Delineation of genetic predisposition to multifactorial disease: a general approach on the threshold of feasibility. PMID- 1733847 TI - Rapid physical mapping of cloned DNA on banded mouse chromosomes by fluorescence in situ hybridization. AB - Physical mapping of DNA clones by nonisotopic in situ hybridization has greatly facilitated the human genome mapping effort. Here we combine a variety of in situ hybridization techniques that make the physical mapping of DNA clones to mouse chromosomes much easier. Hybridization of probes containing the mouse long interspersed repetitive element to metaphase chromosomes produces a Giemsa-like banding pattern which can be used to identify individual Mus musculus, Mus spretus, and Mus castaneus chromosomes. The DNA binding fluorophore, DAPI, gives quinacrine-like bands that can complement the hybridization banding data. Simultaneous hybridization of a differentially labeled clone of interest with the banding probe allows the assignment of a mouse clone to a specific cytogenetic band. These methods were validated by first mapping four known genes, Cpa, Ly-2, Cck, and Igh-6, on banded chromosomes. Twenty-seven additional clones, including twenty anonymous cosmids, were then mapped in a similar fashion. Known marker clones and fractional length measurements can also provide information about chromosome assignment and clone order without the necessity of recognizing banding patterns. Clones hybridizing to each murine chromosome have been identified, thus providing a panel of marker probes to assist in chromosome identification. PMID- 1733848 TI - Human minisatellite alleles detectable only after PCR amplification. AB - We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays. PMID- 1733849 TI - Regional localization of the human G protein alpha i2 (GNAI2) gene: assignment to 3p21 and a related sequence (GNAI2L) to 12p12-p13. AB - Gi alpha proteins, members of the G protein signal transduction family, include a small number of polypeptides: Gi alpha 1 (GNAI1), Gi alpha 2 (GNAI2), and Gi alpha 3 (GNAI3). A cDNA for the human GNAI2 gene has been isolated from a human T cell library and is mapped by chromosomal in situ hybridization to the short arm of chromosome 3 at 3p21. A related sequence, GNAI2L, is mapped by in situ hybridization to the short arm of chromosome 12 at p12-p13. These mapping results are further supported by amplification of GNAI2-specific sequences in a monochromosomal human/rodent somatic cell hybrid containing only human chromosome 3. Of note, these assignments are to chromosome regions in which other G proteins reside. Localization of GNAI2 to 3p21 is of great interest as this region of the short arm of chromosome 3 is frequently involved in rearrangements in various human tumors. PMID- 1733850 TI - Long-range mapping of the gene for the human alpha 5(IV) collagen chain at Xq22 q23. AB - The X-linked kidney disorder known as Alport syndrome (AS) has been shown to be due to mutations in the gene for an alpha 5 chain of type IV collagen that maps to Xq22-23. Using overlapping cDNA clones that represent approximately 90% of this gene and pulsed-field gel electrophoresis, we have constructed a 2.4-Mb long range restriction map around the locus. All of the cDNA clones lie within a 360 kb segment of DNA bounded by CpG islands that contain sites for the rare-cutting enzymes BssHII, MluI, NotI, NruI, SalI, and SfiI. High-resolution PFGE mapping with XhoI shows that the gene is at least 110 kb in size and is one of the largest collagen genes characterized to date. This map will prove useful in the characterization of mutations in individuals affected with AS and will also provide information as to the location of other genes in the region. PMID- 1733851 TI - Cloning and polymerase chain reaction-single-strand conformation polymorphism analysis of anonymous Alu repeats on chromosome 11. AB - We have shown that many of the Alu repeats found in the GenBank database are polymorphic and that this polymorphism can be detected by a simple technique, single-strand conformation polymorphism (SSCP) analysis, after polymerase chain reaction (PCR) amplification of each repeat from DNA of individuals. Here, we describe a method for collecting many anonymous Alu repeats and their flanks in a chromosome-specific phage library and cloning them into plasmids. The flanking single-copy sequences of each repeat in the plasmid were then determined, and 20mer to 30mer segments of these sequences were used as primers for the PCR-SSCP analysis. Many new polymorphic DNA markers on chromosome 11 were obtained with this method. These markers can also serve as sequence-tagged sites for physical mapping of the genome. PMID- 1733852 TI - Assignment of tyrosine-specific T-cell phosphatase to conserved syntenic groups on human chromosome 18 and mouse chromosome 18. AB - Phosphorylation of proteins on tyrosine is crucially involved in signal transduction and mitogenesis and is regulated by both kinases and phosphatases. Recently, a number of soluble and transmembrane receptor-linked protein tyrosine phosphatases (PTPase) have been characterized. Among these is a 48.4-kDa PTPase encoded by a cDNA isolated from a T-lymphocyte library by low-stringency screening with probes derived from placental PTPase 1B. A human T-cell PTPase (PTPT) cDNA and somatic cell hybrids were used to assign a PTPT gene to conserved syntentic groups on human chromosome 18 and on mouse chromosome 18. Two unlinked sequences, one on human chromosome 1, were also detected. PMID- 1733853 TI - Clinical and genetic heterogeneity of Charcot-Marie-Tooth disease. AB - The autosomal dominant forms of hereditary motor and sensory neuropathies include the hypertrophic form (CMT1) and the neuronal form of Charcot-Marie-Tooth disease (CMT2). While at least two distinct loci have been shown to be linked to the CMT1 phenotype (CMT1A and CMT1B, on chromosomes 17 and 1, respectively), whether the CMT2 phenotype results from mutations allelic to either of the CMT1 genes remains unknown. Studying one CMT1 and two CMT2 pedigrees, we were able to exclude the CMT2 disease locus from the region of chromosome 17 (Z = -2.80 at theta = 0.05 for D17S58) where the CMT1A gene maps (Z = +3.67 at theta = 0.00). Similarly, negative lod score values were obtained in CMT2 for the region of chromosome 1 where the CMT1B gene has been located (Z = -3.09 at theta = 0.05 for D1S61). The present study therefore provides evidence for genetic heterogeneity between the hypertrophic and the neuronal forms of Charcot-Marie-Tooth disease and demonstrates that the CMT2 gene is not allelic to either of the CMT1 genes mapped to date. PMID- 1733854 TI - Unique sequence homology in the pericentromeric regions of the long arms of chromosomes 13 and 21. AB - We previously isolated two polymorphic chromosome 21q probes, pVC1.21c (D21S190) and pVC1.34a (D21S149), localized in 21qcen-21q21.2. In addition, pVC1.21c recognized a sequence in 21q22.1-q22.2 and both probes cross-hybridized with non chromosome-21 sequences. In this study we refined the proximal 21q locations of probes pVC1.21c and pVC1.34a to 21q11.1 and demonstrated that they recognize sequences on chromosome 13 but not on chromosomes 14, 15, and 22. Furthermore, the polymorphisms associated with the two loci were assigned to pericentromeric 13q for pVC1.34a and distal 21q for pVC1.21c. Our results are indicative of a region of unique sequence homology in the pericentromeric region of the long arms of chromosomes 13 and 21. PMID- 1733855 TI - An A to T transversion at position -5 of the factor IX promoter results in hemophilia B. AB - The molecular pathology that results in hemophilia B has been determined by many studies to be highly variable. Several point mutations have been identified in a 40-bp region within the Factor IX promoter. These include mutations at nucleotides -20, -6, +8, and +13. Here we report an A to T transversion at position -5 of the Factor IX gene. There is strong circumstantial evidence to support an important role for this region of the Factor IX promoter in the developmental regulation of the gene through the binding of specific transcription factors. PMID- 1733856 TI - Assignment of the gene encoding DNA ligase I to human chromosome 19q13.2-13.3. AB - The gene encoding DNA ligase I has been mapped on human chromosome 19 by analysis of rodent-human somatic cell hybrids informative for this chromosome and by two color fluorescence in situ hybridization. The DNA ligase I gene (LIG1) is localized to 19q13.2-13.3 and is distal to ERCC1, the most telomeric of three DNA repair genes on this chromosome. PMID- 1733857 TI - Mapping of the human gene for the human immunodeficiency virus type 1 enhancer binding protein HIV-EP2 to chromosome 6q23-q24. AB - The human gene encoding the human immunodeficiency virus type 1 enhancer binding protein HIV-EP2 has been isolated. Using Southern analysis of human-rodent somatic cell hybrid DNA with a human HIV-EP2-specific cDNA probe, the HIV-EP2 gene was assigned to chromosome 6. The gene was further localized to the region 6q23-24 by fluorescence in situ hybridization. PMID- 1733858 TI - Assignment of the human heterogeneous nuclear ribonucleoprotein A1 gene (HNRPA1) to chromosome 12q13.1 by cDNA competitive in situ hybridization. AB - Heterogeneous nuclear ribonucleoprotein (HNRP) core protein A1 is a major component of mammalian HNRP particles. The human HNRP A1 protein was shown to be encoded by a 4.6-kb gene, split into 10 exons, belonging to a multigene family of about 30 A1-specific sequences per haploid genome, many of which correspond to pseudogenes of the processed type. Here we report the mapping of the human HNRPA1 gene to band 12q13.1. Localization was performed by nonisotopic in situ hybridization using a phage genomic clone that contains the active HNRPA1 gene as well as 13.5-kb flanking sequences. To suppress hybridization to pseudogene sequences, unlabeled HNRPA1 cDNA was added in excess over the probe to the hybridization mixture. PMID- 1733859 TI - Highly polymorphic (GT)n repeat sequence in intron II of the human MAOB gene. PMID- 1733860 TI - Assignment of the interleukin-2 receptor beta chain gene (Il-2rb) to band E on mouse chromosome 15. PMID- 1733861 TI - A structural analysis of the Sxr region of the mouse Y chromosome. AB - Three genetic functions have been mapped to the minute Sxr (sex-reversed) region of the mouse Y chromosome. These are Tdy, the primary testis determinant; Hya, the locus (either structural or regulatory) controlling the expression of the male-specific minor histocompatibility antigen H-Y; and Spy, a spermatogenic gene. Hya and Spy map to DNA deleted from the Sxr region in the deletion variant Sxrb (the delta Sxrb DNA). With the object of cloning Hya and Spy, we initiated chromosome walking in the delta Sxrb DNA. From three independent loci--Sx1, Zf2, and T5--we have isolated approximately 270 kb of delta Sxrb DNA lying in three contigs of 145, 60, and 65 kb, respectively. Within 17 kb of the 3' end of the Zfy-2 gene, lowcopy repeat elements were found in a region that extends for approximately 35 kb. Probes isolated from this region detect multiple Sxr loci, some of which map to the delta Sxrb DNA present in the T5 contig DNA. Three of these multicopy probes detect delta Sxrb loci not represented in our three contigs, which means that six distinct delta Sxrb loci have now been identified. Here we present a preliminary model of the molecular structure of the DNA in this unique region. PMID- 1733862 TI - Walking, cloning, and mapping with yeast artificial chromosomes: a contig encompassing D21S13 and D21S16. AB - Chromosome 21 has often been used as a model system for the development of genome mapping and cloning strategies in humans. In this report methods for systematic chromosome walking, cloning, and mapping are exemplified in the construction of a 1.5-Mb yeast artificial chromosome (YAC) contig encompassing and extending 400 kb beyond each of the genetic loci D21S13 and D21S16. Isolation of insert-terminal sequences from YACs in this contig provides a set of closely spaced physical markers. These have been used to generate a long-range genomic restriction map. PMID- 1733863 TI - The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome. AB - A recently isolated cDNA clone from the iduronate sulfatase (IDS) gene has been used both to seed a contig of overlapping yeast artificial chromosomes (YACs) and to investigate the molecular defect in patients with Hunter syndrome (MPS II). Six YAC clones were found to span the IDS gene, and those and 14 other YACs were assembled into a 1.2-Mb contig around the gene in Xq27-q28. The physical map of the region identifies several putative CpG islands, suggesting the presence of other genes in the vicinity. DNA from a patient with a translocation breakpoint in the gene also permitted the orientation of the contig in the chromosome. Southern analysis of DNA from 25 unrelated Italian Hunter syndrome patients revealed 4 with deletions or rearrangements in the IDS gene. PMID- 1733864 TI - Assignment of the gene (RLBP1) for cellular retinaldehyde-binding protein (CRALBP) to human chromosome 15q26 and mouse chromosome 7. AB - Cellular retinaldehyde-binding protein (CRALBP) has properties that suggest that it is involved in the visual process and, therefore, potentially with retinal diseases. A human cDNA probe has been used to map this gene to human chromosome 15q26 (somatic cell hybrids and in situ hybridization) and to mouse chromosome 7 by somatic cell hybrids. PMID- 1733865 TI - Allele frequency distribution of the (TG)n(AG)m microsatellite in the apolipoprotein C-II gene. AB - The dinucleotide (TG)n interspersed repetitive sequences are the most abundant microsatellites in the human genome. Using the polymerase chain reaction to amplify a (TG)n(AG)m microsatellite in the first intron of the apo C-II gene, we have detected 15 different alleles in 242 unrelated individuals of French ancestry. The heterozygosity index was 0.85 and codominant Mendelian inheritance of the alleles was observed in individuals from 121 nuclear families. We report that polymorphism at this locus is attributable to length variation at both (TG)n and (AG)m motifs, although the (AG)m motif contains only two alleles differing by one repeat unit. A quadrimodal allele frequency distribution was observed at the (TG)n(AG)m locus. Each of the first three modes comprises one frequent allele and one very rare allele adjacent in size. No alleles of intermediate size were found between the three first modes. The fourth mode encompasses nine alleles that span from 27 to 35 repeat units. We suggest that this distribution reflects the molecular mechanisms by which alleles give rise to one another. PMID- 1733866 TI - Isolation and characterization of a yeast artificial chromosome (YAC) contig around the human steroid sulfatase gene. AB - The region surrounding the steroid sulfatase (STS) locus on Xp22.3 is of particular interest since it represents a deletion hot spot, shares homology with the proximal long arm of the Y chromosome (Yq11.2), and contains genes for several well-described X-linked disorders. Here we describe yeast artificial chromosomes (YACs) covering 450 kb around the STS gene. Eight YAC clones were isolated from a human YAC library. Their STS exon content was determined and the overlap of the clones characterized. Two of the YAC clones were found to contain the entire STS gene. The most proximal and the most distal ends of the YAC contig were cloned but neither of them crossed the breakpoints in any of the previously described patients with entire STS gene deletions. This is consistent with deletions larger than 500 kb in all these patients. One of the YAC clones was found to contain sequences from the STS pseudogene on Yq11.2. Two anonymous DNA sequences, GMGXY19 and GMGXY3, previously mapped in the vicinity of the STS locus, were found within the YAC contig and their assignment with respect to the STS locus was thus possible. This contig is useful for the overlap cloning of the Xp22.3 region and for reverse genetic strategies for the isolation of disease genes in the region. Furthermore, it may provide insight into the molecular mechanisms of deletion and translocation events on Xp22.3 and in the evolution of sex chromosomes. PMID- 1733867 TI - Long-range physical map of the Ly-6 complex: mapping the Ly-6 multigene family by field-inversion and two-dimensional gel electrophoresis. AB - The Ly-6 proteins are encoded by a recently identified multigene family. Much attention has been focused on these proteins because they may be involved in lymphocyte activation, and expression of some of them occurs at critical times in the differentiation of lymphocytes. These features make it important to investigate and to characterize further this family of molecules and the genes that encode them. To aid our investigation of these issues, we have constructed a physical map of the entire Ly-6 complex in the C57BL/6 murine genome using the combined techniques of field-inversion gel electrophoresis (FIGE), phage and cosmid genomic library screening, and two-dimensional DNA electrophoresis. This map spans approximately 1600 kb, and comparison of the FIGE map and cosmids indicates that most of the Ly-6 complex has been isolated in the cosmid clones. PMID- 1733868 TI - Differential diagnosis between Hodgkin's disease and non-Hodgkin's lymphoma. PMID- 1733869 TI - The nature and function of the Hodgkin's cell lectin and its role in lymphocyte agglutination. PMID- 1733870 TI - Role of T cells in the pathogenesis of Hodgkin's disease. PMID- 1733871 TI - Diagnosis and grading of nodular sclerosing Hodgkin's disease: a study of 2190 patients. PMID- 1733872 TI - Lymphocyte-predominance Hodgkin's disease. PMID- 1733873 TI - Immunophenotype of Reed-Sternberg cells. PMID- 1733874 TI - The consensus of committees. PMID- 1733875 TI - X-ray contrast media. PMID- 1733876 TI - Comparative safety of high-osmolality and low-osmolality radiographic contrast agents. Report of a multidisciplinary working group. PMID- 1733877 TI - Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent. AB - We have previously reported that ultrastable lipid-coated microbubbles make a suitable ultrasonic contrast agent in the brain, causing increased intensity of echoes that persists for many hours. We showed that intravenously administered lipid-coated microbubbles accumulate selectively in rat brain gliomas with echogenicity enhancement for up to 1 hour, allowing visualization of the growing lesions 40% (2 days) earlier than can be seen without contrast. This work is a detailed evaluation of the accumulation of the lipid-coated microbubbles in tumor and the effect of the bubbles on the echogenicity of insonified tumors. Using a lipid-specific stain, we measured and characterized the distribution of the bubbles in the brain and tumor. We showed that on the scan, the enhancement of the tumor is accompanied by a change in the signal-to-noise ratio of the echoes from the tumor. We identified characteristic textural changes associated with contrast-enhanced tumor using spectral analysis. PMID- 1733878 TI - Effects of intracoronary administration of contrast media on myocardial high energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol. AB - Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia. PMID- 1733879 TI - Quality of urography and renal clearance of ionic and nonionic contrast media. AB - The authors evaluated whether urographic quality correlated with patient hydration and the level of their renal function, depending on whether they received ionic or nonionic contrast media. One hundred patients with normal serum creatinine levels were randomly assigned to receive intravenous urography with either an ionic high-osmolar or a nonionic low-osmolar contrast medium. Patient hydration was evaluated by measuring urine osmolality in a sample voided just before the examination. The plasma concentration of iodine was determined in a single blood sample drawn approximately 3 hours later. From these determinations the plasma clearance of contrast medium was calculated. The urograms were assessed blindly with regard to nephrographic and pyelographic opacification, as well as overall diagnostic quality. The clearance varied between 42 and 115 mL x minutes-1 x 1.73 m-2. No systematic correlation of practical significance was found between the clearances and the urogram quality. A high urinary osmolality before the examination tended to improve quality with both media. It is not possible to assess glomerular filtration rate from nephrographic and pyelographic opacification, or from overall quality of routine urograms in patients with normal serum creatinine levels. PMID- 1733880 TI - Incompatibility of water-soluble contrast media and intravascular pharmacologic agents. An in vitro study. AB - In vitro incompatibilities between nine water-soluble contrast media and 21 intravascular pharmacologic agents were investigated using naked-eye observation and a centrifuge. Most of the previously reported incompatibilities were verified, and a few new incompatibilities were discovered: phentolamine mesylate with diatrizoate sodium, diatrizoate meglumine, ioxaglate, and iothalamate; diatrizoate meglumine with diazepam and meperidine hydrochloride; and diatrizoate sodium with meperidine hydrochloride. There were no incompatibilities when the pharmacologic agents investigated were mixed with ioxithalamate, iopromide, iopamidol, and iohexol. PMID- 1733881 TI - Effect of flow rate on adherence of unlabeled and indium-111 oxine-labeled leukocytes. AB - Uptake of radioactively labeled leukocytes has been observed in ischemic noninfected regions. Since this may be a flow-related phenomenon, the authors investigated the effect of flow rate on adherence of indium-111 oxine-labeled leukocytes with a model based on the elution patterns of radioactivity and granulocytes from nylon fiber columns. Relative radioactivity adherence (%RA) and relative granulocyte adherence (%GA) agreed closely, indicating that radioactivity retained by the columns is predominantly in the form of viable labeled granulocytes, and that labeled and unlabeled granulocytes have the same adherence characteristics. When other conditions were held constant, but passage speed was varied, %GA and %RA were related to the flow rate in an inverse linear fashion. Decrease in flow rate can lead to increased accumulation of leukocytes. PMID- 1733882 TI - Diagnostic performance of teleradiology in cervical spine fracture detection. AB - This study was done to assess the diagnostic accuracy of high-resolution (5 lp/mm) teleradiology for detecting cervical spine fractures. Single radiographs from 25 patients with and 25 patients without cervical spine fractures were transmitted between two units of our teleradiology system (Dupont DTR 2000) located 5 miles apart. Each image was examined by four readers. Fracture detection accuracy was assessed by generating receiver operating characteristic (ROC) curves and comparing the areas under each reader's curves for original and transmitted images. Two readers had statistically significant better fracture detection using nontransmitted images, whereas two had no significant differences in accuracy. The authors conclude that high resolution in and of itself is not adequate for fracture detection, and that issues concerning image contrast manipulation also will have to be addressed before teleradiology systems can be used for clinical cervical spine fracture screening. PMID- 1733883 TI - Ultrafast computed tomography in experimental pulmonary embolism. AB - Computed tomography (CT) has proven useful in the diagnosis of central pulmonary embolism; however, its ability to detect peripheral emboli has not been established. The authors evaluate the usefulness of ultrafast CT (UFCT) in detecting experimental peripheral pulmonary emboli. Three Gelfoam emboli measuring 0.7 x 1.5 cm were introduced into the pulmonary arteries of each of seven dogs, and contiguous, 3-mm, axial UFCT images from the lung apex to the base were obtained after the administration of a contrast bolus. After scanning, the dogs were killed, and the locations of the emboli were determined by a pulmonary pathologist blinded to the imaging results. Concomitantly, the locations of the emboli on the UFCT images were determined by consensus of three chest radiologists blinded to the autopsy results. All 21 emboli were identified on UFCT images; the locations of the emboli corresponded exactly with the autopsy findings. The authors conclude that UFCT can reliably detect Gelfoam emboli in second- to fourth-division pulmonary vessels. Further studies are needed to determine if in vivo blood clots can be similarly visualized. PMID- 1733884 TI - A fully automated adaptive unsharp masking technique in digital chest radiograph. AB - The authors are developing a fully automated adaptive unsharp masking technique with parameters that depend on regional image features of a digital chest radiograph. A chest radiograph includes various regions such as lung fields, retrocardiac area, and spine. These areas have very different texture patterns and optical densities. Therefore, for best evaluation, it is necessary to enhance the image contrast of each region by an optimal parameter. In the current study, a chest radiograph was automatically divided into three segments (lung field, retrocardiac area, and spine) by using a histogram analysis of pixel values. The lung fields and retrocardiac area were selectively enhanced with a small mask size and mild weighting factors that had been previously determined to be optimal. The spine was enhanced with a large mask size and adequate weighting factors. An observer performance test indicated that this technique provides excellent diagnostic accuracy for simulated nodules in chest radiographs. PMID- 1733885 TI - Computer-aided detection of diffuse liver disease in ultrasound images. AB - The authors are developing an automated method of determining measures of texture in liver ultrasound images to improve the accuracy of diagnosis of diffuse liver abnormalities. In each digitized image, the background trend of pixel values is estimated to isolate the underlying pattern of liver texture. After correcting for background trend, the root mean square (RMS) variation and the first moment of the power spectrum are calculated; these measures have been applied successfully to texture analysis of digital chest radiographs. Background trend corrected measurements detected statistically significant differences in digitized ultrasound images of 11 normal and 11 abnormal livers. Without correction for background trend, the measures are unable to distinguish normal from abnormal liver texture. The authors also investigated the effect on the texture measures of varying several ultrasound imaging parameters in normal patients and in an ultrasound phantom. PMID- 1733886 TI - Computer-assisted fusion of single-photon emission tomographic and computed tomographic images. Evaluation in complicated inflammatory disease. AB - Fusion of single-photon emission computed tomographic (SPECT) and x-ray computed tomographic (CT) images can facilitate the direct comparison of function and anatomy by simultaneously displaying comparable cross-sectional images. A computer-assisted fusion method was used to prospectively evaluate 10 patients with suspected inflammatory disease complicated by an associated condition. CT images were transferred to the nuclear computer. Image fusion was accomplished with standard scaling, rotation, translation, and stretching transformations, using anatomic or external landmarks. SPECT-CT fusion correctly localized the inflammatory process in all 10 cases and facilitated percutaneous drainage or preoperative surgical planning in 6. PMID- 1733887 TI - Magnetic resonance imaging in assessing cartilage changes in experimental osteoarthrosis of the knee. AB - Cartilage degeneration in osteoarthrosis (OA) of the knee generally is believed to precede osseous abnormalities. Because cartilage abnormalities are not readily detected by routine radiography, we investigated the role of magnetic resonance imaging (MRI) in assessing cartilage damage in a goat model for OA. Four goats had the anterior cruciate ligament of one knee severed surgically to create instability and accelerate OA. Two goats each were killed at 4 and 6 weeks, respectively, after walking on the unstable knees. MRI of the knees was performed with Hybrid fat suppression sequences. The images were correlated with gross anatomic sections and histologic analysis of the knees. On gross examination, the unstable knees showed rapid development of thinning, surface irregularity, and focal defects of the cartilage. These findings correlated well with abnormalities detected on the MRIs. In addition, areas of decreased signal intensity in cartilage correlated with histologic evidence of degenerative changes in the cartilage substance, including fragmentation, fibrillary and eosinophilic changes, and chondrocyte proliferation, indicating attempted cartilage repair. Precise correlation of pathologic and MRI data, however, was lacking, related in part to inability to match perfectly the level and orientation of the gross section with that on the MRI examination. PMID- 1733888 TI - Efficient method for selecting cardiac magnetic resonance image locations. AB - Selecting locations for long- and short-axis cardiac magnetic resonance images (MRIs) conventionally requires two preliminary image sets, one to find the plane of the left ventricular (LV) axis and a second to find the axis within that plane. By specifying the LV axis from landmarks on the initial image set, it is possible to go directly to short-axis images without the second set of preliminary images, thus improving efficiency and shortening the duration of the examination. PMID- 1733889 TI - The dark age all around us. PMID- 1733890 TI - Coal worker's pneumoconiosis CT assessment in exposed workers in correlation with radiographic findings. PMID- 1733891 TI - Kidney transplantation in Jerusalem, 1972-89. Kidney Transplant Group. AB - The results of a small transplant program over 18 years are presented. Two hundred and fifty-six transplantations including 36 living donor transplants were performed in 203 patients. Graft survival at 1, 3, 5 and 10 years without and with cyclosporin A treatment was 57%, 49%, 44%, 38%, and 71%, 69%, 58%, -% (respectively). Patient survival was 83%, 67%, 62%, 54%, and 92%, 90%, 68%, -% (respectively). Recent results with cyclosporin A treatment have shown further improvement. Analysis using the COX model shows that age under 30 years, lack of systemic disease, and the use of cyclosporin A and living donors all improved patient survival. More than 10- and 5-year survival was achieved in 78 and 103 patients, respectively, of whom 53 and 81 have good graft function. Local transplant policy and patient material are discussed. PMID- 1733892 TI - Hereditary ovarian cancer: a dilemma in prognosis. AB - Five women in three generations developed ovarian cancer. We closely monitored 36 descendent women in this family who were at high risk for developing this disease. Prophylactic oophorectomy is considered the optimal way to prevent the development of ovarian cancer. In the light of the young age of the women at risk and their strong objection to oophorectomy, we closely monitored the examinees for early signs of cancer for more than 5 years. None of them developed cancer. The dilemma in treatment of women at risk is discussed. PMID- 1733893 TI - Clinical characteristics of patients with fibromyalgia. AB - Fibromyalgia, also known as fibrositis and muscle rheumatism, is a common, noninflammatory, painful musculoskeletal disorder. It is common between the ages of 30 and 60 years and has a female to male ratio of 5 to 1. Essential symptoms of fibrositis are pain, fatigue, disturbed sleep, morning stiffness and local tenderness. Subjective swelling, paresthesia and numbness sometimes occur. Multiple host and environmental factors seem to contribute to the onset and course of fibromyalgia. Modest improvement follows treatment by antidepressive agents, physical measures and reduction in stress. In this study 60 patients with fibromyalgia were investigated and the clinical characteristics of these patients are described and compared with those in other studies. PMID- 1733894 TI - Autonomous hyperparathyroidism not associated with increased aluminum absorption. AB - A single 6-g dose of aluminum hydroxide was given to eight patients on regular hemodialysis before and 3 days after parathyroidectomy (PTX). Serum aluminum levels were measured before and after 5 h after ingestion of aluminum hydroxide to examine indirectly the effects on absorption of aluminum from the gastrointestinal tract of both high and low parathyroid hormone (PTH). Plasma PTH levels fell significantly from 2,724 +/- 1,830 ng/l (mean +/- 1 SD) before PTX to 352 +/- 63 ng/l after PTX. However, no significant change was detected in serum aluminum levels before or after PTX (1.45 +/- 0.96 to 1.92 +/- 0.88 mumol/l before PTX; 2.02 +/- 1.41 to 2.89 +/- 1.19 mol/l after). These findings indicate that in patients with chronic renal failure, high plasma levels of PTH are not associated with significant increases in serum aluminum concentrations after ingestion of a large quantity of aluminum hydroxide. Parathyroid hormone may not enhance intestinal absorption of aluminum in humans. PMID- 1733895 TI - Combined carotid endarterectomy and coronary artery revascularization: a sobering review. AB - The clinical outcome of 99 patients who underwent combined single-stage carotid thromboendarterectomy and coronary artery bypass grafts in three different hospitals over a 15-year period was analyzed. Coronary revascularization was elective in 16 patients, urgent in 46 and emergent in 37 patients. Asymptomatic carotid artery stenosis of greater than or equal to 80% was detected in 79% of patients. Sequential reconstruction of the carotid artery circulation followed by restoration of the coronary circulation was performed in all patients by two separate surgical teams. The population included 79 men and 20 women, with a mean age of 67 +/- 6 years, of whom 53% had a previous myocardial infarction, 59% had hypertension and 49% had a history of smoking. Three or more coronary arteries were revascularized in 90% of patients. The overall major neurological complication rate was 25%, with an 11% stroke rate ipsilateral to the operated carotid. Other major complications included respiratory failure (5%), multisystem failure (8%), and myocardial infarction (8%). The overall mortality was 12%. Ten of the 12 deaths were directly related to the cardiac operation, and 2 died as a result of stroke. We conclude that a combined carotid and coronary artery operation results in a high morbidity and mortality in institutions with excellent records for each operation when performed separately. Whenever possible, these high risk patients should be carefully assessed regarding the need for both procedures, since prophylactic carotid endarterectomy has not been shown to significantly reduce the neurologic risk of coronary bypass. PMID- 1733896 TI - Cigarette smoking and educational level among young Israelis upon release from military service in 1988--a public health challenge. AB - The prevalence of cigarette smoking was determined in a representative sample of Israeli men and women mostly aged 20-22, upon release from military service. In this sample, 47.5% of the men and 30% of the women reported themselves to be current smokers, and 46% and 26% respectively to be current regular smokers. Of the current smokers 80% of the men and 74% of the women took up smoking before entering military service. Educational level at recruitment was strongly associated with age at uptake of smoking, the prevalence of smoking and the number of cigarettes currently smoked per day. Ethnic differences in smoking prevalence after controlling for education were relatively small. Men and women with less than or equal to 11 years of schooling reported twice the smoking prevalence of those with greater than or equal to 12 years, 71 vs. 35% current smokers in men and 56% vs. 26% current smokers in women respectively. Heavy smoking of greater than or equal to 20 cigarettes per day was reported by 51% and 30% of less educated men and women, respectively, compared with 17% and 9% respectively of those with greater than or equal to 12 years of schooling. We conclude that intervention programs directed toward the prevention of uptake of smoking in adolescents should receive high public health priority in Israel, with special emphasis on adolescents prior to military service and focusing on the more susceptible segments of the young population. PMID- 1733897 TI - The relationship between the lupus anticoagulant, anticardiolipin antibodies and antiphospholipid antibodies. PMID- 1733898 TI - Studying tenderness--a clue to understanding fibromyalgia. PMID- 1733899 TI - Medicine and the Ethiopian Jews: report and analysis from Addis Ababa. PMID- 1733900 TI - Severe gastrointestinal bleeding induced by a probable hydroxycoumarin bezafibrate interaction. PMID- 1733901 TI - Considerations in health services planning in an atmosphere of uncertainty: the case of coronary artery bypass surgery in Israel. PMID- 1733903 TI - Annual meeting of the Israel Society of Microbiology. 25-26 March 1991, Ramat Gan, Israel. Abstracts. PMID- 1733902 TI - Acute surgical abdominal disease in schizophrenics. PMID- 1733904 TI - Association of lupus anticoagulant and anticardiolipin antibodies with thrombosis in patients with systemic lupus erythematosus, primary antiphospholipid syndrome and other disorders. AB - Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been associated with thrombotic events and recurrent fetal loss. In order to assess the role of LA with the thrombotic tendency in various disease states we evaluated 38 patients with confirmed LA [tissue thromboplastin index (TTI) greater than 1.3; circulating anticoagulant index (CAI) greater than 15], subgrouped as follows: a) LA associated with systemic lupus erythematosus (SLE) (n = 13); b) primary antiphospholipid syndrome (PAPS) (n = 16); and c) LA associated with other disorders (n = 9). Male/female ratio differed between the groups: 0/13, 6/10 and 4/5, respectively. Venous and arterial thrombotic events were more common in the PAPS group (87%) compared with the SLE group (61%) and the other disorders group (22%). Serum ACA antiphospholipid IgG levels by ELISA were increased in the SLE and PAPS patients, but did not differ between the groups (167 +/- 24 vs. 190 +/- 28 mu respectively). Antiphospholipid IgM levels were higher in the SLE group compared with the PAPS group (127 +/- 15 vs. 67 +/- 16 mu). Mean TTI and CAI levels did not differ between the SLE, PAPS and other disorders groups (1.8 +/- 0.19, 2.8 +/- 0.9, 2.0 +/- 0.3 for TTI; 25 +/- 4, 33 +/ 4, 32 +/- 5 for CAI). Likewise TTI, CAI and ACA levels did not differ in patients with or without thrombosis. We conclude that the prevalence of thrombotic manifestations varies among patients with similar serum intensities of LA and levels of ACA, suggesting that other factors may be involved in the pathogenesis of thrombosis in these patients. PMID- 1733905 TI - Primary and secondary prevention of cancer in Israel. PMID- 1733906 TI - Screening for colorectal neoplasia: a multicenter study in Israel. AB - We report the design and results of the first Israeli multicenter screening program for colorectal neoplasia. The screening protocol comprised a risk questionnaire, fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. A total of 5,601 individuals were screened in five medical centers, 55% being asymptomatic with low or average risk. Colorectal tumors were found in 12.3% of screenees, the majority being adenomas. The risk for large bowel neoplasia was greatest in persons with a personal history of colorectal neoplasia (neoplasia rate 473.2/10(3)) and was increased in those with inflammatory bowel disease, a family history of colorectal tumor, or past history of cured breast cancer. European-born Jews had a 50% greater risk than non-European-born Jews. Persons at high risk were more likely to return for repeat screening than those at low or average risk. However, approximately 15% of persons at high risk actually thought that they were of average risk. Fecal occult blood testing was markedly less reliable than flexible sigmoidoscopy and had a false-negative rate of 84.4%. The results demonstrate that existing medical facilities in Israel can be used to screen at least those individuals with increased risk for colorectal neoplasia. PMID- 1733907 TI - Colon cancer screening in Israel. PMID- 1733908 TI - Screening for colorectal neoplasia in the Tel Aviv area: cumulative data 1979-89 and initial conclusions. AB - We present an analysis comprising the initial 10 years experience with a screening program for colorectal neoplasia in the Tel Aviv area that involved 5,625 screenees. It demonstrated that selective screening, based on pre established epidemiologic criteria and selective screening methodology, resulted in a colorectal neoplasia yield that related directly to the screenee's risk of neoplasia. We have no evidence that the program is life-saving or cost-effective. Medically, however, it yielded early-stage neoplasms that were mainly adenomas, and most cancers were early-stage and noninvasive. Among the screenees 1% had cancer, of which 2/3 were Duke's A or B; 10% had adenomas and 7.3% of these (0.7% of all screenees) had severe dysplasia. Removal of these adenomas has been shown to reduce large bowel cancer incidence. Presently we cannot generally recommend mass screening by the available screening tests, fecal occult blood and endoscopy. However, an outreach case-finding program, based on existing health services, is possible and medically rewarding especially in groups at high risk for neoplasia. PMID- 1733909 TI - Cellular and subcellular localization of tritiated gentamicin in the guinea pig cochlea following combined treatment with ethacrynic acid. AB - Guinea pigs (GPs) receiving one intra-muscular injection of gentamicin (GM) (150 mg/kg) in which 2 mg of tritiated GM (2 mCi) were incorporated, followed 1.5 h later by an intra-cardiac injection of ethacrynic acid (EA) (30 mg/kg) were sacrificed 25 min, 1, 4 and 24 h after the EA injection. Other GPs were treated with one injection of GM or EA alone and sacrificed 24 h later. Cochlear function was monitored by recording VIIIth nerve compound action potential (CAP) responses to clicks at 70 dB peak-equivalent Sound Pressure Level (pe SPL) and CAP audiograms. At 24 h thresholds were significantly elevated for high frequencies only in GPs treated with the GM/EA combination. GM was revealed in the cochlea and kidney by autoradiography using light and electron microscopy. In the kidney GM was already detected in the proximal tubule cells at 25 min and at 24 h. In the cochlea GM was systematically not observed at 25 min. At 1 h a weak labelling was detected in vessels of the stria vascularis and in sensory cells at the base of the cochlea. At 4 h the labelling disappeared in stria vascularis but increased in the hair cells. At 24 h GM labelling was found exclusively in hair cells, particularly outer hair cells, with a gradient from base to apex and from first to 3rd row, this distribution pattern correlating well with the pattern of threshold changes prominent at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733910 TI - Ongoing production of sensory cells in the vestibular epithelium of the chick. AB - Recent studies have shown that the vestibular and auditory systems of some species of birds have the capacity to generate sensory hair cells postnatally. We used a traditional technique, 3H-thymidine autoradiography, and a newer method, bromodeoxyuridine immunocytochemistry, to determine whether ongoing proliferation of hair cells occurs in the intact chick vestibular epithelium. A ten-day course of 3H-thymidine, bromodeoxyuridine, or both was administered to twelve-day-old chicks. Both autoradiographic and immunocytochemical labeling demonstrated ongoing production of supporting cells and Type II hair cells in all chick vestibular organs. No evidence for production of Type I hair cells was seen in this investigation. New sensory cells were distributed throughout the epithelium; there was no peripheral growth zone analogous to that found in other vertebrates. Labeled Type II hair cells were frequently seen immediately above labeled supporting cells. This observation suggests that supporting cells are precursors for new hair cells. The ongoing, postnatal regeneration of vestibular epithelial cells also suggests that this epithelium may retain the potential for repair after trauma or ototoxic damage. PMID- 1733911 TI - Ionic coupling among cells in the organ of Corti. AB - Gap junctions have been demonstrated morphologically among the supporting cells of the mammalian organ of Corti but, in contradistinction to reptiles, evidence for their existence between the supporting cells and hair cells is equivocal. The literature is ambiguous with respect to electrical coupling and dye coupling among the supporting cells, and no coupling of either kind has been demonstrated for the hair cells. We found strong coupling of both kinds among the supporting cells in the cochleas of live Mongolian gerbils and a less stable coupling between the supporting cells and the outer hair cells. The electrical coupling was established by recording alternating receptor potentials in the hair cells and following their decrement in the population of Hensen's cells; the dye coupling, by injecting Lucifer yellow electrophoretically into the hair cells or the supporting cells and investigating its spread to the neighboring cells. The electrical recordings were made by means of microelectrodes filled with either 1.5 or 3 M KCl or 1 M LiCl with 6% Lucifer yellow, the latter used for dye injection. The electrode resistances ranged from about 20 to 60 M omega in the first instance, and from about 50 to 110 M omega, in the second. The electrodes were inserted into the organ of Corti through scala media according to the method of Dallos, Santos-Sacchi and Flock (1982) modified by us. The alternating potential in Hensen's cells was usually larger than in the outer tunnel of Corti and remained practically constant up to the outer margin of the Hensen's-cell population. Its phase was the same as in the outer hair cells. When the dye was injected into a Hensen's cell, it always spread to neighboring Hensen's cells and often to Deiter's cells. Dye injected into outer hair cells (identified according to anatomical and physiological criteria) also spread to Deiter's and Hensen's cells and, usually, to other outer hair cells. Stained cells were identified in surface preparations and, on two occasions, in serial sections from plastic embedded cochleas. PMID- 1733912 TI - Age-dependent disruption of basal lamina and extracellular matrix formation in L proline analog treated otic explants. AB - L-azetidine-2-carboxylic acid, LACA, a naturally occurring vegetable imino acid, can be incorporated into mammal proteins instead of proline. This incorporation has an especially inhibitive effect on collagen secretion. Exposure of embryonic mouse inner ear explants to LACA causes dysmorphogenesis and retarded differentiation, reduces the number of collagen fibrils in the perilymphatic spaces and capsules, and gives rise to a dose-dependent derangement of the basal lamina. In control specimens, both in vivo and in vitro, the inner ear epithelia had a dense contiguous basal lamina overlying a well-developed network of collagen fibrils. When the inner ears were exposed to LACA at a concentration of 150 micrograms per ml of medium, there was a loss of the collagen network and gaps appeared in the basal lamina. At exposure to 300 micrograms LACA/ml, scarcely any collagen fibrils were present and the basal lamina was disrupted in many areas, especially beneath the sensory epithelia. PMID- 1733913 TI - Actin-binding and microtubule-associated proteins in the organ of Corti. AB - Actin-binding and microtubule-associated proteins regulate microfilament and microtubule number, length, organization and location in cells. In freeze-dried preparations of the guinea pig cochlea, both actin and tubulin are found in the sensory and supporting cells of the organ of Corti. Fodrin (brain spectrin) co localized with actin in the cuticular plates of both inner and outer hair cells and along the lateral wall of the outer hair cells. Alpha-actinin co-localized with actin in the cuticular plates of the hair cells and in the head and foot plates of the supporting cells. It was also found in the junctional regions between hair cells and supporting cells. Profilin co-localized with actin in the cuticular plates of the sensory hair cells. Myosin was detected only in the cuticular plates of the outer hair cells and in the supporting cells in the region facing endolymph. Gelsolin was found in the region of the nerve fibers. Tubulin is found in microtubules in all cells of the organ of Corti. In supporting cells, microtubules are bundled together with actin microfilaments and tropomyosin, as well as being present as individual microtubules arranged in networks. An intensely stained network of microtubules is found in both outer and inner sensory hair cells. The microtubules in the outer hair cells appear to course throughout the entire length of the cells, and based on their staining with antibodies to the tyrosinated form of tubulin they appear to be more dynamic structures than the microtubules in the supporting cells. The microtubule associated protein MAP-2 is present only in outer hair cells within the organ of Corti and co-localizes with tubulin in these cells. No other MAPs (1,3,4,5) are present. Tau is found in the nerve fibers below both inner and outer hair cells and in the osseous spiral lamina. It is clear that the actin-binding and microtubule-associated proteins present in the cochlea co-localize with actin and tubulin and that they modulate microfilament and microtubule structure and function in a manner similar to that seen in other cell types. The location of some of these proteins in outer hair cells suggests a role for microfilaments and microtubules in outer hair cell motility. PMID- 1733914 TI - Setting complex tasks to single units in the avian auditory forebrain. I: Processing of complex artificial stimuli. AB - In the auditory forebrain (field L) of the European starling (Sturnus vulgaris), single unit responses were recorded for a wide range of complex stimuli, comprising different forms of amplitude and frequency modulation. About two-third of the units locked to sinusoidal modulation regardless of whether frequency (SFM) or amplitude (SAM) was modulated. On average, however, frequency led to stronger synchronization. Both the proportion of phase locking and its mean strength showed a low-pass dependence on modulation frequency. The lower efficiency of amplitude modulation is also visible in unit responses when SAM is combined with (random) frequency modulation. For the assessment of response strength and its comparison across the tested repertoire of complex stimuli, a new index (REX) is introduced which primarily weighs similarity of the spike trains in identically repeated stimulus runs. Applied to a set of 311 field L neurons, also this approach discloses the two stimulus classes lacking frequency modulation (pure tone and SAM) as the least effective. A new measure for response latency, the Effective Response Delay (ERD), based on the spike-triggered analysis of responses to randomly frequency-modulated sounds (RFM), reflects physiological delays better than conventional latency. So, ERD correction of SAM and SFM Period Histograms allowed to disclose response effective stimulus ranges independent of modulation frequency. PMID- 1733915 TI - Setting complex tasks to single units in the avian auditory forebrain. II. Do we really need natural stimuli to describe neuronal response characteristics? AB - The response characteristic of auditory forebrain neurons in the European starling was established both with artificial stimuli (AS) and a conspecific territorial song as a natural stimulus (NS1). Applying experimenter-centred statistical methods for response detection and for scaling response strength, and spike-triggered analyses for the delimitation of the key sound parameters (spectrotemporal receptive field STRF, Aertsen et al. 1980) the study aimed at disclosing differences in the processing of the two stimulus classes, AS and NS. With the STRF as reference, we find congruence (1) in the best frequency with those determined under sweep and bandpass noise stimulation, (2) in response latency, and (3) in response-intensity dependence, further similarity in the overall frequency characteristic. Partitioning the song into 42 acoustically defined segments allowed to further delimit the response criteria under natural stimulation. They are easily understood from the AS response characteristics: (1) In the neuronal sample as a whole, long segments are more effective than short and, among the short, loud segments are more effective than faint; (2) Units showing their best excitatory response to AS in a certain frequency band are most probably excited by segments with a high proportion of their power concentrated upon or near this band; (3) Units with a slow (build-up) AS response react to a lower number of song segments than those dynamically following AS transients. Our data give no hint towards adaptive, feature detection properties of single neurons in field L. Instead, these neurons appear to base their response solely on the short-time spectrotemporal structure of the stimulus, irrespective of its natural or artificial origin. PMID- 1733916 TI - Middle-ear transmission: acoustic versus ossicular coupling in cat and human. AB - Otologic surgeons consider the action of sound pressure on the cochlear windows to be of major importance in certain cases of middle-ear pathology, yet previously published network models of mammalian middle ears do not include such a mechanism. A unified middle-ear model is developed in which it is assumed that the difference of acoustic pressures acting on the windows adds to the ossicular chain pressure to produce cochlear input. From a network model of the cat middle ear cavities we estimate the contributions of pressures on the cochlear windows for both normal and abnormal cat ears. For the human ear we use the model of Kringlebotn (1988) and measurements of Bekesy (1947). We determine that the pressure difference across the cochlear windows is negligibly small in normal cat and human ears. Thus, it is a reasonable approximation to ignore this mechanism in normal ears. For ears with a drastically altered tympanic membrane and/or ossicular chain, acoustic coupling to the cochlear windows can--to a considerable extent--explain residual hearing in human. The model predicts hearing levels for type IV tympanoplastic reconstructions that agree with the best results obtained surgically. PMID- 1733917 TI - Analysis of possible interactions of an attentional task with cochlear micromechanics. AB - Several contradictory studies have been published regarding the effect of selective attention on cochlear mechanics, possibly modulated through efferent pathways. Click-evoked otoacoustic emissions have been proposed as a highly sensitive tool for testing the hypothesis of such a modulation. In this study, two other types of evoked otoacoustic emissions (i.e. distortion products and stimulus frequency emissions between 1 and 4 kHz) were measured on 20 normal subjects in absence and presence of a visual selective attention task. The duration of measurements at a given frequency was short enough to eliminate possible artefacts due to long-time averaging. No significant change was observed in these signals, considered as probes of cochlear micromechanics. It is concluded that in this set of experimental conditions, selective attention has a negligible effect on peripheral sensitivity. PMID- 1733918 TI - Triple fluorochrome labeling of cochlear bone growth. AB - A new technique is described which measures the extent and time course of intracochlear bone formation after cochlear implantation in an experimental animal model. A series of fluorescent histochemical markers is used to delineate the amount of intracochlear bone deposition during specified time periods. PMID- 1733919 TI - The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. AB - The three-dimensional structure of recombinant human lymphotoxin (residues 24-171 of the mature protein) has been determined by x-ray crystallography at 1.9-A resolution (Rcryst = 0.215 for I greater than 3 sigma (I)). Phases were derived by molecular replacement using tumor necrosis factor (TNF-alpha) as a search model. Like TNF-alpha, lymphotoxin (LT) folds to form a "jellyroll" beta-sheet sandwich. Three-fold related LT subunits form a trimer stabilized primarily by hydrophobic interactions. A cluster of 6 basic residues around the 3-fold axis may account for the acid lability of the trimer. Although the structural cores of TNF-alpha and LT are similar, insertions and deletions relative to TNF-alpha occur in loops at the "top" of the LT trimer and significantly alter the local structure and the overall shape trimer is highly conserved. The sites of two mutations (Asp-50 and Tyr-108) that abolish the cytotoxicity of LT are contained within poorly ordered loops of polypeptide chain that flank the cleft between neighboring subunits at the base of the molecule, suggesting that the receptor recognizes an intersubunit binding site. PMID- 1733920 TI - Smooth muscle myosin is composed of homodimeric heavy chains. AB - Vertebrate smooth muscle myosin heavy chains (MHCs) exist as two isoforms with molecular masses of 204 and 200 kDa (MHC204 and MHC200) that are generated from a single gene by alternative splicing of mRNA (Nagai, R., Kuro-o, M., Babij, P., and Periasamy, M. (1989) J. Biol. Chem. 264, 9734-9737). A dimer of two MHCs associated with two pairs of myosin light chains forms a functional myosin molecule. To investigate the isoform composition of the MHCs in native myosin, antibodies specific for MHC204 were generated and used to immunoprecipitate purified bovine aortic smooth muscle myosin from a solution containing equal amounts of each isoform. MHC204 quantitatively removed from this mixture was completely free of MHC200. Immunoprecipitation of the supernatant with an antiserum that recognizes both isoforms equally well revealed that only MHC200 remained. We conclude that only homodimers of MHC204 and MHC200 exist under these conditions. A method is described for the purification of enzymatically active MHC204 and myosin on a protein G-agarose high performance liquid chromatography column containing immobilized MHC204 antibodies. We show, using an in vitro motility assay, that the movement of actin filaments by myosin containing 204-kDa heavy chains (0.435 +/- 0.115 microns/s) was not significantly different from that of myosin containing 200-kDa heavy chains (0.361 +/- 0.078 microns/s) or from myosin containing equal amounts of each heavy chain isoform (0.347 +/- 0.082 microns/s). PMID- 1733921 TI - Cloning and expression of an intron-less gene for AKAP 75, an anchor protein for the regulatory subunit of cAMP-dependent protein kinase II beta. AB - The A-Kinase Anchor Protein AKAP 75 (formerly designated bovine brain P75) is a particulate brain protein that avidly binds the regulatory subunit (RII beta) of cAMP-dependent protein kinase II beta (Bregman, D. B., Hirsch, A.H. and Rubin, C.S. (1991) J. Biol. Chem. 266, 7207-7213). The formation of stable AKAP 75.RII beta complexes provides a potential mechanism for targeting physiological signals carried by cAMP to specific effector sites within neurons and other brain cells. We have now cloned and characterized the AKAP 75 gene. Its coding sequence is novel and unexpectedly short (1284 base pairs) and contains no introns. When the AKAP 75 gene was transfected into HEK 293 cells, a new RII beta-binding protein with an apparent Mr of 75,000 accumulated. A high proportion (approximately 65%) of the AKAP 75 gene product was excluded from the cytoplasm and was recovered in the 40,000 x g pellet derived from disrupted transfected cells. In contrast, cells transfected with a construct encoding 249 amino acids from the central and C-terminal regions of AKAP 75 produced an RII beta-binding protein (apparent Mr = 45,000) that was exclusively cytosolic. AKAP 75 is a novel protein composed of only 428 amino acid residues (Mr = 47,878). A highly acidic C-terminal region mediates the binding of RII beta (and cAMP-dependent protein kinase II beta), whereas a positively charged N-terminal segment contains structural features that are essential for the association of AKAP 75 with the cytoskeleton and/or intracellular membranes. PMID- 1733922 TI - Charge polarity reversal inverses the specificity of neutral endopeptidase-24.11. AB - Attempts to change enzyme specificity by charge polarity reversal have so far met with little success, probably due to a destabilization of the resulting ion pair in an environment naturally optimized for the inverted pair. In the zinc metallopeptidase neutral endopeptidase-24.11 (EC 3.4.24.11), Arg102, involved in substrate binding, is probably located at the edge of the active site (Bateman, R.C., Jr., Kim, Y.-A., Slaughter, C., and Hersh, L.B. (1990) J. Biol. Chem. 265, 8365-8368; Beaumont, A., Le Moual, H., Boileau, G., Crine, P., and Roques, B.P. (1991) J. Biol. Chem. 266, 214-220). This environment may be favorable for polarity reversal, as in water the energies of reverse ion pairs would be identical. We show here that, while mutating Arg102 to Glu reduces the specificity of a C-terminally negatively charged substrate 16-fold, it increases that of a substrate with an optimally positioned positive charge 29-fold. The concept of charge polarity reversal can be extended to other zinc metallopeptidases, and the mutated enzyme could also have applications in the enantiomeric separation of unnatural amino acids. PMID- 1733923 TI - A single amino acid deletion at the amino terminus of influenza virus hemagglutinin causes malfolding and blocks exocytosis of the molecule in mammalian cells. AB - I am investigating the role of protein folding in the transport of influenza virus hemagglutinin (HA), a membrane-bound protein, along the exocytotic pathway. From a previous work (Gething, M.-J., McCammon, K., and Sambrook, J. (1986) Cell 46, 939-950), it has been shown that a subset of alterations of the COOH-terminal sequences of the HA molecule inhibit folding and impede its transport to the cell surface. Current studies establish that the integrity of the NH2-terminal sequences of the HA is essential for assembly and transport of the molecule. Mutants lacking just 1 or 2 amino acids immediately COOH-terminal to the signal cleavage site are translocated and core glycosylated, but also incorrectly folded. The mutant molecules are not terminally glycosylated and are thus confined inside the cells. A hypothesis will be presented to explain why sequences at opposite ends of the HA molecule are essential for the assembly of native structures and why correct folding is necessary for transport along the exocytotic pathway of mammalian cells. PMID- 1733924 TI - Wortmannin, a microbial product inhibitor of myosin light chain kinase. AB - We have found that a fungal strain, Talaromyces wortmannin KY12420, produces a potent inhibitor of smooth muscle myosin light chain kinase (MLCK). This active product, designated as MS-54, was isolated and purified from the culture broth of the fungus and identified as wortmannin. The inhibition of MLCK by wortmannin was prevented by a high concentration of ATP. The activity of the catalytic domain, which was disclosed by partial tryptic digestion, was also inhibited by wortmannin. These results suggest that wortmannin acts at or near to the catalytic site of the enzyme. It was shown clearly by kinetic analyses, preincubation studies, and dialysis experiments that the inhibitory action of wortmannin on MLCK was irreversible. Under the condition of preincubation for 3 min, 0.3 microM wortmannin inhibited the activity of MLCK, while 10 microM wortmannin had no effect on the activities of cAMP-dependent protein kinase, cGMP dependent protein kinase, and calmodulin-dependent protein kinase II, and had little effect on protein kinase C activity. These data expressed clearly the marked selectivity of the compound for MLCK. Furthermore, wortmannin also inhibited both the phosphorylation of myosin light chain and the contraction in rat thoracic aorta stimulated with KCl, which indicates the effectiveness of the compound in the cellular level as an MLCK inhibitor. PMID- 1733925 TI - The active site of creatine kinase. Affinity labeling of cysteine 282 with N-(2,3 epoxypropyl)-N-amidinoglycine. AB - Epoxycreatine (N-(2,3-epoxypropyl)-N-amidinoglycine) is an affinity label of creatine kinase that irreversibly and completely inactivates the enzyme (Marletta, M. A., and Kenyon, G. L. (1979) J. Biol. Chem. 254, 1879-1886). To identify active site residues of rabbit muscle creatine kinase, the site of modification of it by epoxycreatine has been determined. Separation by high performance liquid chromatography of a tryptic digest of [14C]epoxycreatine modified creatine kinase yielded two radiolabeled peptides. The larger of these consisted of amino acids Ala-266 through Arg-291 and was labeled with epoxycreatine at Cys-282. Attempts to purify completely the other labeled peptide were not successful; however, it was possible to obtain, by tandem mass spectrometry, a collision-induced dissociation spectrum of it from a mixture of several peptides. This peptide was a fragment (amino acids Val-279 through Arg 291) of the previously identified peptide and was also labeled at Cys-282. Model studies with cysteine and epoxycreatine have demonstrated that opening of the oxirane ring occurs by attack of the cysteine thiolate at the terminal carbon of the epoxide. These results are consistent with previous studies on the base lability of the label; however, a carboxyl group in the active site is not labeled, as had been previously suggested. These results provide evidence that Cys-282 is located in or near the creatine-binding site and will also be important in identifying and delineating the boundaries of the active site of creatine kinase. PMID- 1733926 TI - The predominant form of secreted colony stimulating factor-1 is a proteoglycan. AB - Colony stimulating factor-1 (CSF-1) is a homodimeric glycoprotein that humorally regulates the proliferation and differentiation of mononuclear phagocytic cells and locally regulates cells of the female reproductive tract. Alternative splicing of the human CSF-1 mRNA leads to alternative expression of the CSF-1 homodimer as a secreted glycoprotein or as a membrane-spanning molecule with cell surface biological activity. In the present study, analysis of immunoaffinity purified CSF-1 from mouse L929 cell medium by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) indicated that CSF-1 is predominantly secreted as highly sulfated species of 375- and 250-kDa with a smaller amount of a 100-kDa species. Analysis by gel filtration in 4 M guanidine HCI buffer, indicated that, in contrast to the 100-kDa species, the highly sulfated species exhibit anomalously high molecular weights and self-association on SDS-PAGE similar to the dermatan sulfate proteoglycan, biglycan. The three predominant CSF-1 species were shown to be an 80-kDa homodimer, an 80-kDa/50-kDa heterodimer, and a 50-kDa homodimer. The 80-kDa subunit contained a single 18-kDa chondroitin sulfate chain that was absent from the 50-kDa subunit. Furthermore, treatment of the 80- and 50-kDa subunits, synthesized in the presence of tunicamycin, with chondroitinase ABC, neuraminidase, and endo-alpha-N-acetyl galactosaminidase reduced their apparent molecular masses to 60 and 25 kDa, respectively. These results are consistent with intracellular proteolytic cleavage of the 80-kDa chondroitin sulfate containing subunits from the membrane spanning CSF-1 precursor at a point carboxyl-terminal to the single consensus sequence for glycosaminoglycan addition and cleavage of the 50-kDa glycoprotein subunit at a position aminoterminal to this site. The predominance of the proteoglycan form of secreted CSF-1, which represents only 3-4% of the total trichloroacetic acid-precipitable counts released from 35SO4(2-)-labeled L cells, has important implications for regulation by this growth factor. PMID- 1733927 TI - IciA protein, a specific inhibitor of initiation of Escherichia coli chromosomal replication. AB - Specific binding of IciA protein to the 13-mers in the origin of a minichromosome (oriC) inhibits initiation of replication in vitro by blocking the opening of this region effected by the initiator DnaA protein (Hwang, D.S., and Kornberg, A. (1990) Cell 63, 325-331). Isolation of the iciA gene (Thony, B., Hwang, D.S., Fradkin, L., and Kornberg, A. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4066-4070) has made possible the construction of an IciA-overproducing strain, which in turn has simplified the isolation of a large quantity of the protein, indistinguishable from that of the wild-type strain. Based on sedimentation and gel filtration, the IciA protein is an elongated dimer of a 33.4-kDa subunit. The specific binding of IciA protein to the 13-mers was stable for 2 h at 30 degrees C. The amounts of IciA protein, detected by immunoassays, increased 4-fold compared with levels (about 100 dimers) in log-phase cells whereas levels of DnaA protein decreased upon entry of cells into the stationary phase. PMID- 1733928 TI - Activation by G protein beta gamma subunits of agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptors and rhodopsin. AB - We have partially purified a protein kinase that phosphorylates muscarinic receptors (mAChR) in the presence of agonists and have shown that the phosphorylation is stimulated by the beta gamma subunits of the GTP binding protein Go (Haga, K., and Haga, T. (1990) FEBS Lett. 268, 43-47). We report here that rhodopsin is also phosphorylated in a light-dependent manner by the same kinase preparation and that beta gamma subunits derived from Gs, Gi, and Go stimulate the phosphorylation of both rhodopsin and mAChRs. The rhodopsin- and mAChR-phosphorylating activities were eluted in the same fractions using a purification procedure that is essentially the same as that used for the purification of beta-adrenergic receptor kinase (Benovic, J.L., Strasser, R.H., Caron, M.G., and Lefkowitz, R.J. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 2797 2801) and were inhibited by low concentrations of heparin, an inhibitor of beta adrenergic receptor kinase, (IC50 = 15 nM), suggesting that both mAChR and rhodopsin are phosphorylated by the same or very similar kinase(s) belonging to the beta-adrenergic receptor kinase family. G protein beta gamma subunits increased the Vmax of the phosphorylation of rhodopsin 12-fold. Kinetic data were consistent with the assumptions that the protein kinase (mAChR kinase) binds rhodopsin and beta gamma subunits in a random order and that the reaction rate is proportional to concentration of the ternary complex. By contrast, the light dependent phosphorylation of rhodopsin by the rhodopsin kinase was not stimulated by the beta gamma subunits. These results indicate that beta gamma subunits may interact with and activate the mAChR kinase but not rhodopsin kinase and suggest that the beta gamma subunit of G proteins may take part in the desensitization of G protein-linked receptors. PMID- 1733929 TI - Isolation and characterization of a novel class of plant antimicrobial peptides form Mirabilis jalapa L. seeds. AB - We have isolated from seeds of Mirabilis jalapa L. two antimicrobial peptides, designated Mj-AMP1 and Mj-AMP2, respectively. These peptides are highly basic and consist of 37 and 36 residues for Mj-AMP1 and Mj-AMP2, respectively. Both peptides contain three disulfide bridges and differ from one another only by 4 amino acids. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the reduced and unreduced peptides suggests that the peptides associate into dimers in their native form. The Mj-AMPs exhibit a broad spectrum of antifungal activity since they are active against all 13 tested plant pathogenic fungi. Concentrations required for 50% inhibition of fungal growth vary from 6 to 300 micrograms/ml for Mj-AMP1 and from 0.5 to 20 micrograms/ml for Mj-AMP2. These peptides were also active on two tested Gram-positive bacteria but were apparently nontoxic for Gram-negative bacteria and cultured human cells. Although the Mj-AMPs show sequence similarity to mu-agatoxins, a class of insecticidal neurotoxic peptides isolated from the venom of spiders, they do not affect pulse transmission in insect nerves. PMID- 1733930 TI - Protein L from Peptostreptococcus magnus binds to the kappa light chain variable domain. AB - Protein L is an immunoglobulin light chain-binding protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus. The major variable region subgroups of human kappa and lambda light chains were tested for protein L binding; V kappa I, V kappa III, and V kappa IV bound protein L, whereas no binding occurred with proteins of the V kappa II subgroup or with any lambda light chain subgroups. Studies of the protein L binding capacity of naturally occurring VL fragments, and VL- and CL-related trypsin- and pepsin derived peptides prepared from a kappa I light chain, localized the site of interaction to the VL domain. The affinity constant for the binding to an isolated V kappa I fragment was comparable to that for the native protein (Ka 0.9 x 10(9) M-1 and Ka 1.5 x 10(9) M-1, respectively). No binding occurred with CL related fragments. Extensive reduction and alkylation of the V kappa fragment or the native kappa chain resulted in complete loss of protein L binding. Although it is possible, from comparative amino acid sequence data, to identify certain VL framework region residues that account for the selective binding of protein L by kappa I, kappa III, and kappa IV proteins, our studies indicate that this interaction is essentially dependent upon the tertiary structural integrity of the kappa chain VL domain. PMID- 1733931 TI - Insertional mutagenesis of Bordetella pertussis adenylate cyclase. AB - We developed an improved method of linker insertion mutagenesis for introducing 2 or 16 codons into the Bordetella pertussis cyaA gene which encodes a calmodulin dependent adenylate cyclase. A recombinant kanamycin resistance cassette, containing oligonucleotide linkers, was cloned in plasmids which carried a truncated cyaA gene, fused at its 3' end to the 5' end of the Escherichia coli lacZ gene, specifying the alpha-peptide. This construction permitted a double selection for in-frame insertions by using screening for kanamycin resistance and for lactose-positive phenotype, resulting from alpha-complementation. We showed that most of the two-amino acid insertions within the N-terminal moiety of the catalytic domain of adenylate cyclase abolished enzymatic activity and/or altered the stability of the protein. All two-amino acid insertions within the C-terminal part of adenylate cyclase resulted in fully stable and active enzymes. These results confirm the modular structure of the catalytic domain of adenylate cyclase, previously proposed on the basis of proteolytic studies. Two-amino acid insertions between residues 247-248 and 335-336 were shown to affect the calmodulin responsiveness of adenylate cyclase, suggesting that the corresponding region in the enzyme is involved in the binding of calmodulin or in the process of calmodulin activation. In addition, we have identified within the primary structure of adenylate cyclase several permissive sites which tolerate 16-amino acid insertions without interfering with the catalytic activity or calmodulin binding. By inserting foreign antigenic determinants into these permissive sites the resulting recombinant adenylate cyclase toxin could be used to deliver specific epitopes into antigen-presenting cells. PMID- 1733932 TI - The human blood fluke Schistosoma mansoni synthesizes a novel type of glycosphingolipid. AB - Previous studies have shown that the glycoprotein oligosaccharides synthesized by adult Schistosoma mansoni, the organism responsible for human schistosomiasis, are unusual in that they contain terminal beta-GalNAc residues and lack sialic acid. These observations and other studies indicating that schistosome glycoproteins and glycolipids are antigenic in infected animals led us to investigate the structures of the glycosphingolipids synthesized by these organisms and to determine whether they are structurally related to those synthesized by their vertebrate hosts. For our studies, adult schistosomes were metabolically radiolabeled with either [3H]galactose or [3H]glucosamine, and the newly synthesized glycosphingolipids were isolated and characterized. The major glycosphingolipids synthesized by adult schistosomes were found to be galactosylceramide and glucosylceramide. The adult worms synthesized no lactosylceramide (Gal beta 1-4Glc-ceramide), a common constituent of vertebrate cells; however, another disaccharide-containing glycosphingolipid cleavable by ceramide glycanase was found. The results of compositional and methylation analyses and exoglycosidase treatments demonstrated that this ceramide disaccharide has the structure GalNAc beta 1-4Glc-ceramide. We also found that extracts of adult schistosomes are unable to transfer Gal from UDP-Gal to glucosylceramide, whereas extracts of Chinese hamster ovary cells, as a control, are able to do so, confirming that schistosomes are unable to synthesize lactosylceramide. Low levels of higher molecular weight glycosphingolipids were also found to be synthesized by adult schistosomes, and although their levels were too small to allow definitive characterization, compositional analyses indicated that they also contained GalNAc. We have tentatively designated the new disaccharide structure GalNAc beta 1, 4Glc- the "schistocore", which may represent a new type of glycosphingolipid core series. PMID- 1733933 TI - Cooperative cyanide dissociation from ferrous hemoglobin. AB - Rapid reduction of cyano-met hemoglobin (Hb+CN-) leads to the formation of an intermediate species, the cyanide derivative of ferrous hemoglobin, which dissociates to unliganded hemoglobin because of the extremely low affinity of the ligand for the ferrous heme iron. The properties of the intermediate were studied by transient spectroscopy in human hemoglobin and its isolated alpha and beta chains, in the presence and absence of CO. When mixing with dithionite, the time courses of reduction of the heme iron and dissociation of cyanide overlap considerably; addition to the reaction mixture of the redox indicator methyl viologen considerably increases the rate of reduction and allows unequivocal determination of the spectroscopic and kinetic properties of the intermediate. The results show that (i) the dissociation of cyanide from the isolated alpha and beta chains (as well as the (alpha CO)2(beta + CN-)2 hybrid) is a simple process; (ii) the two chains display similar rate parameters, but show spectroscopic inequivalence, both in the Soret and the visible regions; (iii) cooperative effects are shown to control the rate of dissociation of cyanide from hemoglobin, similarly to what happens for oxygen; and (iv) allosteric effectors (typically inositol hexaphosphate) increase the overall rate of dissociation by stabilization of the T state. We have, therefore, shown for the first time that the dissociation of cyanide from ferrous hemoglobin is controlled by the quaternary state, thereby adding one more ligand to the analysis of the structure function relationships in hemoglobin. PMID- 1733934 TI - The disulfide structure of bovine pituitary basic fibroblast growth factor. AB - Basic fibroblast growth factor has 4 cysteine residues in its amino acid sequence, two of which are perfectly conserved within the fibroblast growth factor family of proteins suggesting a disulfide bond at this position. Furthermore, thiol titration of bovine pituitary basic fibroblast growth factor (bFGF) indicates the presence of two free thiols, which is consistent with an intramolecular disulfide. Direct analysis of natural and recombinant fibroblast growth factor proteins have not confirmed the existence of such a disulfide. Instead, the two nonconserved cysteines of bFGF purified from bovine pituitaries are S-thiolated with glutathione. Inclusion of 75 mM N-ethylmaleimide during the homogenization of the pituitaries effectively blocks the S-thiolation, demonstrating that this modification is an artifact of the purification procedure. Analysis of the N-ethylmaleimide purified bovine pituitary bFGF suggests that the natural protein is in the correct redox state when all 4 cysteines are in the reduced form. PMID- 1733935 TI - Critical functional requirement for the guanidinium group of the arginine 41 side chain of human epidermal growth factor as revealed by mutagenic inactivation and chemical reactivation. AB - In a preliminary study we demonstrated that the formation of the epidermal growth factor (EGF) receptor-ligand complex requires the participation of the highly conserved arginine 41 side chain of the growth factor peptide (Engler, D.A., Montelione, G.T., and Niyogi, S.K. (1990) FEBS Lett. 271, 47-50). In an attempt to gain further insight into the nature of this interaction(s), we used both site directed mutagenesis and chemical modification reagents to produce human EGF (hEGF) analogues with altered chemical properties of the residue 41 side chain. Eight mutant analogues of hEGF were generated, substituting arginine 41 with lysine, glutamine, isoleucine, tyrosine, glycine, alanine, aspartate, or glutamate. Although each of the mutant analogues was able to displace wild-type hEGF fully in receptor competition binding assays, affinity of the receptor for the mutants was substantially reduced, varying from 0.4 to less than 0.01% of that observed for wild-type growth factor. At sufficiently high concentrations these mutants were able to stimulate DNA synthesis in mouse keratinocytes. Substitution of lysine for arginine 41 reduced the receptor affinity 250-fold from that observed for wild type, despite retention of the positive electrostatic charge. The lysine substitution leaves a reactive amine at position 41 and made it possible, using amine-specific chemical modification reagents, to produce selected arginine homologues that were tested for their effects on receptor binding, receptor tyrosine kinase activation, and stimulation of DNA synthesis in mouse keratinocytes. The reaction of lysine 41 with methyl acetimidate resulted in a lysineacetamidine product which only partially restored activity of the lysine hEGF mutant. However, reaction with O-methylisourea resulted in generation of an arginine 41 homologue (homoarginine) which restored full activity. The results indicate that the chemical properties inherent in the guanidinium group of the arginine 41 side chain of hEGF are responsible for optimal receptor-ligand association. PMID- 1733936 TI - Purification and characterization of transforming growth factor-beta 2.3 and beta 1.2 heterodimers from bovine bone. AB - A unique form of transforming growth factor-beta (TGF-beta), TGF-beta 2.3 heterodimer, has been purified from bovine bone extract. TGF-beta 2.3 migrated as a single 25-kDa band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas under reducing conditions it migrated as a 12.5 kDa band. The TGF-beta 2.3 reacted positively with anti-TGF-beta 2 and anti-TGF-beta 3 antibodies on immunoblots. Equal levels of TGF-beta 2 and TGF-beta 3 sequences were detected by N-terminal sequencing. TGF-beta 2.3 eluted as a single sharp peak by reverse-phase high performance liquid chromatography. However, prior reduction of the protein with dithiothreitol resulted in the protein eluting in two peaks, one containing predominantly TGF-beta 3 and the other containing predominantly TGF-beta 2. TGF-beta 2.3 inhibited proliferation of mink lung epithelial cells and promoted the formation of colonies of normal rat kidney fibroblasts in culture with specific biological activity similar to those of TGF beta 1 and TGF-beta 2. These results demonstrate that the protein is TGF-beta 2.3 heterodimer, consisting of one polypeptide chain each of TGF-beta 2 and TGF-beta 3 linked by one or more disulfide bonds. In addition, TGF-beta 1.2 heterodimer, previously found only in porcine platelets, has also been purified from bovine bone extract. PMID- 1733937 TI - Topology of the hydrophobic membrane-bound components of the histidine periplasmic permease. Comparison with other members of the family. AB - The membrane-bound complex of periplasmic permeases comprises two hydrophobic proteins which have been hypothesized to be integral membrane-spaninning proteins. We have investigated the topological organization of the hydrophobic components of the Salmonella typhimurium histidine permease, HisQ and HisM. Both proteins are digested by trypsin and proteinase K when either inside-out or right side-out membrane vesicles are used. Therefore, these proteins are exposed to both surfaces of the membrane. Digestion with carboxypeptidase and binding studies with antibodies directed against the carboxyl terminus of HisQ and HisM have localized their carboxyl termini to the inside surface of the cytoplasmic membrane. Aminopeptidase digestion suggests periplasmic localization of their amino termini. Alkaline phosphatase fusions to HisQ and HisM indicate the existence of five spanners in both proteins. The periodicity and orientation of spanners and loops in HisQ and HisM match those of the five carboxyl-terminal spanners of MalF, the only other hydrophobic component of the periplasmic permeases for which topological information is available. An alignment of the sequences of all known hydrophobic components of periplasmic permeases is presented which indicates clear conservation of secondary structure and some conservation of primary sequence. The structural conservation of the components is discussed, and a role for a hydrophilic loop containing a conserved sequence (the EAA loop) is proposed. PMID- 1733938 TI - Identification of the protein responsible for hepatic system N amino acid transport activity. AB - In the liver, glutamine utilization may be limited by the rate of transport across the plasma membrane by the System N carrier. System N-mediated transport activity has been solubilized from rat liver plasma membrane, partially purified, and then reconstituted into proteoliposomes. To identify the System N carrier protein, monoclonal antibodies were generated against the protein fraction enriched for System N activity. Two antibodies , 3E1-2 and 1E7-3, inhibited System N activity in hepatocytes. These antibodies also immunoprecipitated System N activity from a mixture of solubilized proteins and were specific for antigen recognition in that neither immunoprecipitated System A activity. The antibody recognized a single protein of molecular size 100 kDa by immunoblot analysis. Recognition of this protein by the antibody increased in parallel with the enrichment of System N activity in solubilized membrane fractions. These data suggest that a 100-kDa plasma membrane protein mediates System N transport activity in rat hepatocytes. PMID- 1733939 TI - Search for the heparin antithrombin III-binding site precursor. AB - The last step of heparin biosynthesis is thought to involve the action of 3-O sulfotransferase resulting in the formation of an antithrombin III (ATIII) binding site required for heparin's anticoagulant activity. The isolation of a significant fraction of heparin chains without antithrombin III-binding sites and having low affinity for ATIII suggests the presence of a precursor site, lacking the 3-O-sulfate group. Porcine mucosal heparin was depolymerized into a mixture of oligosaccharides using heparin lyase. One of these oligosaccharides was derived from heparin's ATIII-binding site. In an effort to find the ATIII-binding site precursor, the structures of several minor oligosaccharides were determined. A greater than 90% recovery of oligosaccharides (on a mole and weight basis) was obtained for both unfractionated and affinity-fractionated heparins. An oligosaccharide arising from the ATIII-binding site precursor was found that comprised only 0.8 mol % of the oligosaccharide product mixture. This oligosaccharide was only slightly enriched in heparin having a low affinity for ATIII and only slightly disenriched in high affinity heparin. The small number of these ATIII-binding site precursors, found in unfractionated and fractionated heparins, suggests the existence of a low ATIII affinity heparin may not simply be the result of the incomplete action of 3-O-sulfotransferase in the final step in heparin biosynthesis. Rather these data suggest that some earlier step, involved in the formation of placement of these precursor sites, may be primarily responsible for high and low ATIII affinity heparins. PMID- 1733940 TI - Site-directed mutagenesis of the phosphate-binding consensus sequence in Escherichia coli adenylosuccinate synthetase. AB - Adenylosuccinate synthetases from different sources contain an N-terminal glycine rich sequence GDEGKGK, which is homologous to the conserved sequence GXXXXGK found in many other guanine nucleotide-binding proteins or enzymes. To determine the role of this sequence in the structure and function of Escherichia coli adenylosuccinate synthetase, site-directed mutagenesis was performed to generate five mutant enzymes: G12V (Gly12----Val), G15V (Gly15----Val), G17V (Gly17--- Val), K18R (Lys18----Arg), and I19T (Ile19----Thr). Comparison of the kinetic properties of the wild-type enzyme and those of the mutant enzymes revealed that the sequence is critical for enzyme activity. Replacement of Gly12, Gly15, or Gly17 with Val, or replacement of Lys18 with Arg, resulted in significant decreases in the kcat/Km values of the enzyme. Because the consensus sequence GXXXXGK(T/S) has been found in many GTP-binding proteins, isoleucine at position 19 in the E. coli adenylosuccinate synthetase was changed to threonine to produce the sequence GDEGKGKT. This mutation, which more closely resembles the consensus sequence, resulted in a 160-fold increase in the Km value for substrate GTP; however, there were no great changes for the other two substrates, IMP and aspartate. Based on these data, we suggest that the N-terminal glycinerich sequence in E. coli adenylosuccinate synthetase plays a more important role in enzyme catalysis than in substrate binding. In addition, a hydrophobic amino acid residue such as isoleucine, leucine, or valine, rather than threonine, may play a critical role in GTP binding in adenosuccinate synthetase. These findings suggest that the glycine-rich sequence in adenylosuccinate synthetase functions differently relative to those in other GTP binding proteins or enzymes. PMID- 1733941 TI - Tolerance of T4 lysozyme to proline substitutions within the long interdomain alpha-helix illustrates the adaptability of proteins to potentially destabilizing lesions. AB - To investigate the ability of a protein to accommodate potentially destabilizing amino acid substitutions, and also to investigate the steric requirements for catalysis, proline was substituted at different sites within the long alpha-helix that connects the amino-terminal and carboxyl-terminal domains of T4 lysozyme. Of the four substitutions attempted, three yielded folded, functional proteins. The catalytic activities of these three mutant proteins (Q69P, D72P, and A74P) were 60-90% that of wild-type. Their melting temperatures were 7-12 degrees C less than that of wild-type at pH 6.5. Mutant D72P formed crystals isomorphous with wild-type allowing the structure to be determined at high resolution. In the crystal structure of wild-type lysozyme the interdomain alpha-helix has an overall bend angle of 8.5 degrees. In the mutant structure the introduction of the proline causes this bend angle to increase to 14 degrees and also causes a corresponding rotation of 5.5 degrees of carboxyl-terminal domain relative to the amino-terminal one. Except for the immediate location of the proline substitution there is very little change in the geometry of the interdomain alpha-helix. The results support the view that protein structures are adaptable and can compensate for potentially destabilizing amino acid substitutions. The results also suggest that the precise shape of the active site cleft of T4 lysozyme is not critical for catalysis. PMID- 1733942 TI - Comparison of the enzymatic and biochemical properties of human insulin-degrading enzyme and Escherichia coli protease III. AB - The enzymatic and biochemical properties of human insulin-degrading enzyme and Escherichia coli protease III have been compared. Both enzymes were found to degrade insulin in such a way that its receptor binding activity was rapidly lost but its precipitability in trichloracetic acid was only slightly decreased. Both enzymes were also found to be inhibited by chelating agents. The bacterial enzyme, which could be purified in large amounts, was found to contain 0.6 mol of zinc per mol of enzyme but no detectable manganese. The mammalian enzyme but not the bacterial one was inhibited by a sulfhydryl alkylating agent. The two enzymes also differed in substrate specificity. The mammalian enzyme degraded insulin much better than insulin-like growth factor II, whereas the bacterial enzyme degraded them equally. The mammalian enzyme could be labeled by cross-linking to insulin = bombyxin II much greater than insulin-like growth factor I and II much greater than relaxin, while the bacterial enzyme was labeled by insulin-like growth factor II greater than insulin = insulin-like growth factor I much greater than relaxin much greater than bombyxin. Finally, sucrose gradient centrifugation and cross-linking studies both in vitro and in vivo indicated that active human enzyme partially existed as a homo- or heterodimer, whereas the bacterial enzyme was active as a monomer. PMID- 1733943 TI - Sequence complementarity between the 5'-terminal regions of mRNAs for rat mitochondrial cytochrome P-450c27/25 and a growth hormone-inducible serine protease inhibitor. A possible gene overlap. AB - Recently we reported that a P-450c27/25 cDNA probe hybridizes to two RNA species of about 1.9 and 2.3-2.4 kilobase pairs (kb) in some rat tissues. To understand the molecular relationship between the two mRNAs, we have isolated and characterized a cDNA for the larger, previously uncharacterized 2.3-kb mRNA species. The 2.3-kb cDNA is identical to the previously reported 1.9-kb P 450c27/25 cDNA excepting a 400-nucleotide-long 5' extension. The terminal 291 nucleotides of this extension exhibit 100% complementarity with the 5'-translated region of the mRNA belonging to a family of growth hormone-inducible serine protease inhibitors (SPI). Northern blot analysis, using strand-specific probes, and S1 nuclease protection revealed the presence of the 2.3-kb mRNA exhibiting the sequence characteristics of the larger cDNA. These results were further confirmed by polymerase chain reaction amplification of reverse transcribed RNA. Expression of the 2.3-kb cDNA in COS cells resulted in the correct mitochondrial targeting of a 52-kDa protein exhibiting the properties of P-450c27/25. Furthermore, both the 1.9- and 2.3-kb mRNAs appear to direct the synthesis of a similarly sized 55-kDa precursor protein in a reticulocyte lysate system. Restriction mapping, polymerase chain reaction amplification and partial sequencing of a 25-kb genomic DNA clone suggest the proximal location of the SPI and the P-450c27/25 protein coding regions in the rat genome on either side of a common overlap region. The results also show that the P-450c27/25 mRNAs are regulated by growth hormone in parallel to the SPI mRNAs. These results collectively suggest that a growth hormone-inducible SPI family mRNA and the P 450c27/25 mRNA are encoded by two closely linked, possibly overlapping genes. PMID- 1733944 TI - Long range effects of amino acid substitutions in the catalytic chain of aspartate transcarbamoylase. Localized replacements in the carboxyl-terminal alpha-helix cause marked alterations in allosteric properties and intersubunit interactions. AB - A single alpha-helical polypeptide segment of 21 amino acids near the carboxyl terminus of the catalytic chain of aspartate transcarbamoylase from Escherichia coli has been shown recently to be important for the in vivo folding of the chains and assembly of the enzyme (Peterson, C. B., and Schachman, H. K. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 458-462). Calorimetric measurements on purified mutant enzymes showed that single amino acid replacements within this secondary structural element affect the overall thermal stability of the oligomeric enzyme and the energetics of the interactions between polypeptide chains within the holoenzyme. Studies presented here demonstrate that marked changes in cooperativity occur due to single amino acid substitutions. Replacement of Gln288 by either Ala or Glu leads to a striking increase in the Hill coefficient of the holoenzymes and a substantial increase in the aspartate concentration corresponding to one-half Vmax. In contrast, the isolated catalytic trimers harboring these same substitutions were similar in activity to the wild-type subunit, with the same affinity for aspartate as indicated by the values of Km. Substituting Ala for the only charged residue in the helix, Arg296, caused a marked reduction in enzyme activity, as well as a greatly reduced stability of the holoenzyme due to a substantial weakening of the interactions between the catalytic and regulatory subunits. A subunit exchange method was used to demonstrate the changes in interchain interactions resulting from the amino acid substitutions and to show the additional weakening upon the binding of the bisubstrate ligand, N-(phosphonacetyl)-L-aspartate, at the active sites. Taken together, the results on this series of mutant enzymes illustrate how the effects of single amino acid replacements in one element of secondary structure are propagated throughout the molecule to positions remote from the site of the substitution. PMID- 1733945 TI - Effects of Ca2+ on the kinetics of phosphate release in skeletal muscle. AB - The process of phosphate dissociation during the muscle cross-bridge cycle has been investigated by photoliberation of inorganic phosphate (Pi) within skinned fibers of rabbit psoas muscle. This permitted a test of the idea that Ca2+ controls muscle contraction by regulating the Pi release step of the cycle. Photoliberation of Pi from structurally distinct "caged" Pi precursors initiated a rapid tension decline of up to 12% of active tension, and this was followed by a slower tension decline. The apparent rate constant of the fast phase, kPi, depended on both [Pi] and [Ca2+], whereas the slow phase generally occurred at 2 4 s-1. At maximal Ca2+, kPi increased in a nonlinear manner from 43 +/- 2 s-1 to 118 +/- 7 s-1, as Pi was raised from 0.9 to 12 mM. This was analyzed in terms of a three-state kinetic model in which a force-generating transition is coupled to Pi dissociation from the cross-bridge. As Ca(2+)-activated tension was reduced from maximal (Pmax) to 0.1 Pmax, (i) kPi decreased by up to 2.5-fold, (ii) the relative amplitude of the rapid phase increased 2-fold, and (iii) the relative amplitude of the slow phase increased about 6-fold. Changes in the rapid phase are compatible with Ca2+ influencing an apparent equilibrium constant for the force-generating transition. By comparison, kPi was faster than the rate constant of tension redevelopment, ktr, and was influenced less by Ca2+. Ca2+ effects on the caged Pi transient cannot account for the large effects of Ca2+ on actomyosin ATPase rates or cross-bridge cycling kinetics but may be a manifestation of reciprocal interactions between the thin filament and force-generating cross bridges, and may represent Ca2+ regulation of the distribution of cross-bridges between non-force-and force-generating states. PMID- 1733946 TI - Cyclohexadienyl dehydratase from Pseudomonas aeruginosa. Molecular cloning of the gene and characterization of the gene product. AB - The gene encoding cyclohexadienyl dehydratase (denoted pheC) was cloned from Pseudomonas aeruginosa by functional complementation of a pheA auxotroph of Escherichia coli. The gene was highly expressed in E. coli due to the use of the high-copy number vector pUC18. The P. aeruginosa cyclohexadienyl dehydratase expressed in E. coli was purified to electrophoretic homogeneity. The latter enzyme exhibited identical physical and biochemical properties as those obtained for cyclohexadienyl dehydratase purified from P. aeruginosa. The activity ratios of prephenate dehydratase to arogenate dehydratase remained constant (about 3.3 fold) throughout purification, thus demonstrating a single protein having broad substrate specificity. The cyclohexadienyl dehydratase exhibited Km values of 0.42 mM for prephenate and 0.22 mM for L-arogenate, respectively. The pheC gene was 807 base pairs in length, encoding a protein with a calculated molecular mass of 30,480 daltons. This compares with a molecular mass value of 29.5 kDa determined for the purified enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since the native molecular mass determined by gel filtration was 72 kDa, the enzyme probably is a homodimer. Comparison of the deduced amino acid sequence of pheC from P. aeruginosa with those of the prephenate dehydratases of Corynebacterium glutamicum, Bacillus subtilis, E. coli, and Pseudomonas stutzeri by standard pairwise alignments did not establish obvious homology. However, a more detailed analysis revealed a conserved motif (containing a threonine residue known to be essential for catalysis) that was shared by all of the dehydratase proteins. PMID- 1733947 TI - Sulfhydryl groups on yeast ribosomal proteins L7 and L26 are significantly more reactive in the 80 S particles than in the 60 S subunits. AB - The sulfhydryl-directed fluorescent reagent, 5-iodoacetamidofluorescein (IAF), reacts differently with proteins from the 60 S ribosomal subunit of Saccharomyces cerevisiae when this subunit is free as opposed to being contained within the 80 S ribosome. When the 80 S ribosomes and the free 60 S subunits were labeled with IAF, the specific fluorescence intensity (fluorescence intensity unit/A260 60 S subunit) of the subsequently derived 60 S was 16.3 and 5.4, respectively. Gel analysis showed that proteins L7 and L26 were selectively labeled and contained greater than 90% of the total fluorescent label, when 80 S ribosomes were labeled. When free 60 S subunits were labeled, six additional proteins were labeled. Both types of modified 60 S subunits were equally capable to support protein synthesis in vitro. Reassociation of the IAF-labeled derived and free 60 S subunits with unmodified 40 S subunits resulted in a maximum of 5-7% decrease and a 3-fold increase, respectively, in the fluorescence intensity without a shift in the emission maxima. The data suggest that ribosomal proteins L7 and L26 contain SH groups that respond to ribosomal subunit association and become more reactive in the intact ribosome than in the subunit. The environments of some or all of the additionally labeled proteins are also sensitive to subunit reassociation. PMID- 1733948 TI - Tissue-specific alternative splicing of the beta-galactoside alpha 2,6 sialyltransferase gene. AB - The rat alpha 2,6-sialyltransferase gene produces three different sized mRNAs (4.7, 4.3, and 3.6 kilobases (kb)) which exhibit striking tissue-specific expression. Recently, we characterized the cDNA and genomic organization of the 4.3-kb mRNA which is unique to rat liver. In this report cDNAs of the 4.7-kb mRNA found in most tissues and the 3.6-kb mRNA(s) unique to kidney have been cloned and characterized as well as the corresponding genomic sequences which differed from those of the previously characterized 4.3-kb mRNA. The 4.7-kb mRNA was found to be identical to the 4.3-kb mRNA with the exception of two additional exons at the 5'-untranslated end of the transcript. The constitutively expressed 4.7-kb mRNA therefore codes for the same sialyltransferase as the liver-restricted 4.3 kb mRNA. The additional 5'-exons of the 4.7-kb mRNA are located at least 15-40 kb upstream of the promoter responsible for the production of the 4.3-kb liver message. The 3.6-kb mRNA of rat kidney was found to be comprised of three transcripts of similar size. They were only expressed in kidney and were found to be generated from the alpha 2,6-sialyltransferase gene by alternative splicing and alternative promoter utilization. The results reveal the complexity of the alpha 2,6-sialyltransferase gene which produces at least five transcripts via alternative splicing in a tissue-specific fashion. PMID- 1733949 TI - Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. AB - Autotaxin (ATX) is a potent human motility-stimulating protein that has been identified in the conditioned medium from A2058 melanoma cells. This protein has been purified to homogeneity utilizing a strategy involving five column steps. Homogeneity of ATX was verified by two-dimensional gel electrophoresis. The molecular size of ATX is 125 kDa, and it has an isoelectric point of 7.7 +/- 0.2. Purified ATX was digested with cyanogen bromide and trypsin, and the resulting ATX peptides were purified by reverse-phase high performance liquid chromatography. Eleven peptides were subjected to amino acid sequence analysis, and 114 residues were identified. The partial amino acid sequences and the amino acid composition obtained for ATX show that it does not exhibit any significant homology to known growth factors or previously described motility factors. At picomolar concentrations, ATX stimulates both random and directed migration of human A2058 melanoma cells. Pretreatment of the melanoma cells with pertussis toxin abolishes the response to purified ATX, indicating that ATX stimulates motility through a receptor acting via a pertussis toxin-sensitive G protein. PMID- 1733950 TI - Inhibition of interleukin 3 and granulocyte-macrophage colony-stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases. AB - Interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM CSF) stimulate the proliferation of several kinds of cultured hematopoietic cell lines. Growth signals from IL-3 and GM-CSF cause accumulation of active Ras.GTP complexes in PT18 mouse mast cell line (Satoh, T., Nakafuku, M., Miyajima, A., and Kaziro, Y. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 3314-3318). In this paper we describe the effect of herbimycin A, a tyrosine kinase-specific inhibitor, on the activation of Ras. The increase of Ras.GTP induced by IL-3 and GM-CSF diminished in cells treated with 0.5 approximately 1 micrograms/ml of herbimycin A for 24 h prior to the addition of the growth factors. Under this condition, the extent of phosphorylation on tyrosine residues of proteins decreased. However, the activity of cAMP-dependent protein kinase and protein kinase C did not change. Growth of cells in the presence of IL-3 or GM-CSF was also completely inhibited. These observations suggest that tyrosine kinases are involved in the pathways between IL-3 and GM-CSF receptors and Ras and that they are essential for the growth stimulated by these growth factors. PMID- 1733951 TI - Lymphotoxin is expressed as a heteromeric complex with a distinct 33-kDa glycoprotein on the surface of an activated human T cell hybridoma. AB - We characterized the membrane-associated form of lymphotoxin (surface LT) on the activated II-23.D7 T cell hybridoma. Antibodies to rLT precipitated both surface LT and a distinct 33-kDa glycoprotein (p33). Because p33 and surface LT were antigenically unrelated, their coprecipitation suggested a physical association of p33 and surface LT on the membrane. Pulse-chase analysis indicated that LT and p33 associate with each other early in the LT biosynthetic pathway, precluding the possibility that LT is secreted and bound to p33 or a surface receptor. Furthermore, no p33 was associated with the secreted form of LT. Isoelectric focusing of surface LT and p33 under nondenaturing and denaturing conditions confirmed that surface LT and p33 existed as a complex. Treatment of cells with a high concentration of salt or with acid indicated that surface LT is a peripheral membrane protein. Although secreted LT is a homologous trimer, protein cross linking studies revealed that surface LT existed as a monomer associated with a dimer of p33. Together the results demonstrate a novel mechanism for stable membrane expression of LT by activated T cells. PMID- 1733952 TI - New insights into the import mechanism of the ferredoxin precursor into chloroplasts. AB - We have investigated the import pathway of the nuclear-encoded chloroplast protein ferredoxin. By using purified precursor protein and washed intact chloroplasts in a defined in vitro uptake system, we show that preferredoxin is fully import-competent by itself. In addition, we show also that the in vitro, in a wheat germ lysate, synthesized preferredoxin is not stably associated with another protein. Import is dependent only on ATP and does not require the presence of cytosolic proteins. Translocation could be largely stimulated by the thiol reducing agent dithiothreitol (DTT). To determine whether DTT acts on the precursor or on the chloroplast, we modified the 5 cysteines in the precursor by a reaction with iodoacetamide, thereby preventing the formation of disulfide bridges in the precursor. The import of this modified precursor was still stimulated by the addition of DTT, indicating that DTT had a stimulating effect on the chloroplast import machinery. In the case of the modified precursor, the import must have taken place without iron-sulfur cluster attachment in the stroma. The modified precursor could be imported with a similar efficiency as the parent precursor showing that import takes place independently from cofactor assembly. PMID- 1733953 TI - The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters. AB - Calreticulin (CR) is a calcium binding protein that resides in the endoplasmic and sarcoplasmic reticulum and is reactive with human Ro/SS-A autoimmune sera. We have used human CR cDNA to isolate a human 6-kilobase genomic clone that contains 529 base pairs upstream of the presumed transcription start site, 9 exons, 8 introns, and several hundred base pairs 3' of a polyadenylation sequence. Analysis of the human CR promoter region reveals a number of potential regulatory sites also found in the human GRP78, GRP94, and protein disulfide isomerase promoters, including multiple Sp1 and CCAAT consensus sequences, an AP-2 recognition sequence (absent in protein disulfide isomerase), and multiple GC rich areas. DNA footprint and gel shift analysis on the CR 5'-flanking region demonstrates an area that is bound by protein found in human but not murine nuclear extracts. This sequence is homologous with previously determined regulatory sequences of the human GRP78 and GRP94 promoters. These data indicate that CR, GRP78, GRP94, and protein disulfide isomerase may in part have similar transcriptional regulation and suggest that their gene products while structurally distinct may have similar functions or co-functions. These observations are of additional interest as all four of these genes encode acidic proteins that localize to the endoplasmic reticulum. PMID- 1733954 TI - Neither amino nor carboxyl termini are required for function of the sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain. AB - Antibodies were raised against synthetic peptides corresponding to several regions of the rat brain gamma-aminobutyric acid (GABA) transporter. According to our model, this glycoprotein has 12 transmembrane alpha-helices with both amino and carboxyl termini located in the cytoplasm. The antibodies recognized the intact transporter on Western blots. Upon papain treatment, a reconstitutively active transporter can be isolated upon lectin chromatography (Kanner, B. I., Keynan, S., and Radian, R. (1989) Biochemistry 28, 3722-3728). The papainized transporter runs on sodium dodecyl sulfate-polyacrylamide gels as a broad band with an apparent molecular mass between about 58 and 68 kDa as compared to 80 kDa for the untreated transporter. The transporter fragment was recognized by all the antibodies, except for that raised against the amino terminus. Pronase cleaves the transporter to a relatively sharp 60-kDa band, which reacts with the antibodies against the internal loops but not with either the amino- or the carboxyl-terminal. This pronase-treated transporter, upon isolation by lectin chromatography, was reconstituted. It exhibits full GABA transport activity. This activity exhibits the same features as the intact system including an absolute dependence on sodium and chloride as well as electrogenicity. We conclude that the amino- and carboxyl-terminal parts of the transporter, possibly including transmembrane alpha-helices 1, 2, and 12, are not required for the transport function. PMID- 1733955 TI - Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with a truncated N-terminal domain. A potential mechanism for differential intracellular localization within mineralocorticoid target cells. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) is thought to confer specificity on the nonselective Type I adrenocorticoid receptor by converting glucocorticoids to receptor-inactive metabolites in mineralocorticoid target tissues. S1 nuclease analyses using a rat liver 11-HSD probe demonstrated tissue specific expression of the 5' region of the 11-HSD gene in the liver, lung, and kidney not evident in previous studies. Renal tissue contained a unique protected species which mapped to a position within the coding region, consistent with a divergence in liver and kidney protein sequences. Screening of a rat kidney cDNA library resulted in the isolation of several clones (11-HSD1B) noncolinear in their 5' regions with the liver sequence (11-HSD1A). Nucleic acid sequence analysis showed that the divergent clones code for a protein lacking a 26-amino acid NH2-terminal putative membrane-spanning signal peptide. The deletion of the leader sequence from the microsomal 11-HSD1A protein may result in a nuclear localization of the 11-HSD1B isoform. The renal 11-HSD1A and 11-HSD1B species increased coordinately during ontogeny and in parallel with the developmental surge in glucocorticoids. At least three alternate sites of polyadenylation were found to be utilized by the 11-HSD gene. Southern blot analysis showed the presence of a single gene in the rat. This study shows the expression of a kidney specific 11-HSD isoform which may protect the Type I adrenocorticoid receptor from occupation by glucocorticoids in the nucleus of a mineralocorticoid target cell. PMID- 1733956 TI - A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine. AB - We report purification of an 18-kDa heparin-binding growth factor secreted from human cancer cells which is homologous to a developmentally regulated, neurotrophic factor, heparin-binding growth-associated molecule/pleiotrophin (HB GAM/PTN; Merenmies, J., and Rauvala, H. (1990) J. Biol. Chem. 265, 16721-16724; Li, Y. S., Milner, P. G., Chauhan, A. K., Watson, M. A., Hoffman, R. M., Kodner, C. M., Milbrandt, J., and Deuel, T. F. (1990) Science 250, 1690-1694). We have purified the protein from tissue culture supernatants of human breast cancer cells (MDA-MB 231) and have used soft agar cloning of an epithelial cell line (SW 13) to detect its growth stimulating activity. A 32,000-fold purification was achieved by isoelectric focusing, heparin affinity chromatography, and reversed phase high pressure liquid chromatography. The molecular mass of the protein was confirmed by gel filtration chromatography in the presence of detergent and bioassay of the fractions. The N-terminal sequence was homologous to HB-GAM/PTN, and polymerase chain reaction amplification and DNA sequencing confirmed that the respective transcript was present in the cancer cells. We conclude that HB GAM/PTN can function as a tumor growth factor in addition to its role during neuronal development. PMID- 1733957 TI - The bacteriophage phi 29 DNA polymerase, a proofreading enzyme. AB - The bacteriophage phi 29 DNA polymerase, involved both in the protein-primed initiation and elongation steps of the viral DNA replication, displays a very processive 3',5'-exonuclease activity acting preferentially on single-stranded DNA. This exonucleolytic activity showed a marked preference for excision of a mismatched versus a correctly paired 3' terminus. These characteristics enable the phi 29 DNA polymerase to act as a proofreading enzyme. A comparative analysis of the wild-type phi 29 DNA polymerase and a mutant lacking 3',5'-exonuclease activity indicated that a productive coupling between the exonuclease and polymerase activities is necessary to prevent fixation of polymerization errors. Based on these data, the phi 29 DNA polymerase, a model enzyme for protein-primed DNA replication, appears to share the same mechanism for the editing function as that first proposed for T4 DNA polymerase and Escherichia coli DNA polymerase I on the basis of functional and structural studies. PMID- 1733958 TI - Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis. AB - Epidermal cell differentiation inhibitor (EDIN) is a recently discovered protein which inhibits terminal differentiation of cultured keratinocytes (Sugai, M., Enomoto, T., Hashimoto, K., Matsumoto, K., Matsuo, Y., Ohgai, H., Hong, Y.-M., Inoue, S., Yoshikawa, K., and Suginaka, H. (1990) Biochem. Biophys. Res. Commun. 173, 92-98). The amino acid sequenced deduced from the EDIN gene has revealed that EDIN shares high amino acid sequence homology with the exoenzyme C3 of Clostridium botulinum (Inoue, S., Sugai, M., Murooka, Y., Paik, S.-Y., Hong, Y. M., Ohgai, H., and Suginaka, H. (1991) Biochem. Biophys. Res. Commun. 174, 459 464), which has been shown to ADP-ribosylate the rho/rac proteins (members of the small GTP-binding protein family). We show here that EDIN ADP-ribosylates rhoB p21 in time- and dose-dependent manners in a cell-free system. Kinetic studies of the ADP-ribosylation and peptide mapping of the reaction products of rhoB p21 by EDIN and C3 suggest that the mode of action of the ADP-ribosylation by EDIN is quite similar to that by C3 and that the ADP-ribosylation site of rhoB p21 by EDIN is presumably the same as that by C3. Proteins in epidermal membranes and keratinocyte homogenate with Mr values of about 22,000 are ADP-ribosylated by EDIN or C3. Treatment of cultured human keratinocytes by EDIN or C3 results in an inhibition of terminal differentiation and a stimulation of growth of the cells. Moreover, EDIN and C3 injected into adult mouse skin induce hyperplasia of epidermis. These results suggest that EDIN and C3 affect growth and differentiation of keratinocytes by ADP-ribosylation of protein(s) with a Mr of about 22,000, which may be the rho/rac proteins or related proteins. PMID- 1733959 TI - Organization of the regulatory elements and nuclear activities participating in the transcription of the human apolipoprotein B gene. AB - The human apolipoprotein B (apoB) promoter region (-150 to +124) is transcriptionally active in HepG2 and CaCo-2 but not in HeLa cells. In the present study, we demonstrate that transcription of the human apoB gene in hepatic cells is achieved through the interaction of proteins that bind to five regulatory elements, I (-118 to -98), II (-112 to -94), III (-86 to -62), IV (-72 to -53), and V (-53 to -33). Elements I, IV, and V can bind to bacterially expressed enhancer-binding protein (C/EBP) although with different affinities. In addition, elements I, IV, and V interact with at least two other heat-stable nuclear factors, designated NF-BA2 and NF-BA3, that are distinct from C/EBP. These activities have been separated by ion exchange chromatography and shown to produce footprints in elements I, IV, and V that are similar to those obtained with C/EBP. Element II is recognized by three activities designated NF-BCB1, NF BCB2, and NF-BCB3, which have been separated by heparin-Sepharose chromatography. Saturation mutagenesis of the region established that they belong to a family of proteins recognizing the same motif, 5'-AAAAGCAAACAG-3'. Substitution mutations in element II that abolish binding of all three activities in vitro also reduce hepatic transcription in vivo to 10% of control, indicating that the binding of NF-BCB1, NF-BCB2, and NF-BCB3 activities is required for efficient transcription of the apoB gene. Furthermore, element III is recognized by the previously characterized nuclear factor NF-BA1, the binding of which is essential for the transcriptional activation of the apoB gene in hepatic and intestinal cells. PMID- 1733960 TI - Initiation of transcription by T7 RNA polymerase as its natural promoters. AB - A kinetic assay has been developed to measure the strength of natural T7 promoters. By determining the rate of appearance of initiation products in the presence of constant concentrations of T7 RNA polymerase, an incomplete mixture of ribonucleoside triphosphates, and increasing promoter concentrations, a maximum rate of product formation (Vmax) and a promoter concentration giving half of the maximal activity ([P]Vmax/2) can be determined for any cloned T7 promoter. On supercoiled plasmids, it was found that the [P]Vmax/2 measured for the six promoters phi 1.1B, phi 1.3, phi 3.8, phi 6.5, phi 10, and phi 13 ranged from 3.4 +/- 1.1 to 12.0 +/- 2.4 nM while the Vmax values showed no significant trends. On plasmids that had been linearized by cleavage at a single site with a restriction endonuclease, the cloned T7 promoters assayed fell into two broad classes that appear to be characterized by the T7 class II and III promoters. Generally, the class II promoters required higher promoter concentrations to produce half of the maximum rates of initiation ([P]Vmax/2 values) than the class III promoters. The [P]Vmax/2 values for the class II promoters ranged from 20 +/- 2.7 to 23 +/- 3.6 nM, while the [P]Vmax/2 values for the class III promoters phi 10 and phi 13 were 13 +/- 1.6 nM and 7.8 +/- 1.4 nM. The one exception is the class III promoter phi 6.5 whose [P] Vmax/2 (17 +/- 5 nM) falls between the [P]Vmax/2 values of the class II promoters and the strong class III promoters. The Vmax values measured on linear templates are variable, but it appears that phi 10 is more active than the other five promoters. PMID- 1733961 TI - Temperature-induced post-translational over-modification of type I procollagen. Effects of over-modification of the protein on the rate of cleavage by procollagen N-proteinase and on self-assembly of collagen into fibrils. AB - Previous observations suggested that incubating fibroblasts at elevated temperature caused over-modification of type I procollagen by post-translational enzymes because of a delay in folding of the collagen triple helix. Here, human skin fibroblasts were incubated at 40.5 instead of 37 degrees C, and the type I procollagen secreted into the medium was isolated. Analysis of the protein indicated that there was an increase of about 5 residues of hydroxylysine/alpha chain and about 1 residue of glycosylated hydroxylysine/alpha chain. Assays with procollagen N-proteinase indicated that the N-propeptide of the over-modified collagen was cleaved at a decreased rate, apparently because the over modification altered the conformation-dependent cleavage site for the enzyme. Assays in a system for assembly of collagen into fibrils demonstrated that the over-modified protein had a higher critical concentration for self-assembly. Also, the fibrils formed from the over-modified collagen at 31 and 29 degrees C had smaller diameters than fibrils formed from normal type I collagen. The results provide direct evidence for earlier suggestions that post-translational over-modification of a fibrillar collagen can alter the morphology of the fibrils formed. The results also indicate that some of the biological consequences of the mutations in type I procollagen causing heritable disorders must be ascribed to the effects of post-translational over-modifications that frequently occur as secondary consequences of changes in the primary structure of the protein. PMID- 1733962 TI - Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidylcholine-derived diglyceride in human neutrophils. Involvement of phospholipase D and direct evidence for a positive feedback signal of protein kinase. AB - Complement receptor (CR)-mediated phagocytosis is associated with an increased accumulation of diglyceride (sn-1,2-diacylglycerol and/or 1-O-alkyl-2-acyl glycerol) in human neutrophils. The C3bi-mediated increase in diglyceride (5-20 min) was only partially impaired when phosphoinositide-specific phospholipase C (PLC) activity was abolished by reduction of cytosolic free Ca2+. At an early time point (1 min), however, diglyceride production was barely detectable in control cells, whereas production was considerable in cells with a reduced cytosolic free Ca2+ concentration. C3bi stimulation of 32P-labeled neutrophils caused a rapid and significant breakdown of [32P]phosphatidylcholine (PC) which was not affected by inhibition of Ca(2+)-dependent phosphoinositide-specific PLC. Thus, PC hydrolysis could be involved in C3bi-induced diglyceride formation. Stimulation of cells labeled with [3H]1-O-alkyl-lyso-PC ([3H]alkyl-lyso-PC), resulted in an increased formation of [3H]1-O-alkyl-phosphatidic acid ([3H]alkyl PA) and a later and slower formation of [3H]1-O-alkyl-diglyceride ([3H]alkyl diglyceride); this suggests activation of phospholipase D (PLD). When these labeled cells were stimulated in the presence of 0.5% ethanol a marked accumulation of [3H]1-O-alkyl-phosphatidylethanol ([3H]alkyl-PEt) was observed in both controls and calcium-reduced cells, further strengthening the suggested involvement of PLD activity. In parallel with the sustained increase in diglyceride formation, CR-mediated phagocytosis was also associated with phosphorylation of a cellular protein kinase C substrate (MARCKS). Therefore it seems reasonable to suggest a causal relationship between C3bi-induced PLD activation, which results in diglyceride formation, and activation of protein kinase C. In electropermeabilized cells which were incapable of ingesting particles, C3bi particles were still able to activate PLD and induce formation of diglyceride. This signaling event must therefore be triggered by binding of particles to the cell and not by the engulfment process. Most importantly, introduction of the protein kinase C inhibitor peptides, PKC(19-36) and PKC(19 31), into these permeabilized cells resulted in a clear reduction of the C3bi induced production of diglyceride, indicating that CR-mediated activation of protein kinase C directly triggers a positive feedback mechanism for additional diglyceride formation. Taken together, these data further clarify the mechanisms of CR-mediated diglyceride formation and give added support to the concept that protein kinase C plays an important role in the phagocytic process. PMID- 1733963 TI - Synthetic model proteins. Positional effects of interchain hydrophobic interactions on stability of two-stranded alpha-helical coiled-coils. AB - We have designed a model protein that consists of two identical 35-residue polypeptide chains, parallel and in-register arranged in a two-stranded alpha helical coiled-coil structure. This structure is stabilized by interchain hydrophobic interactions between leucine residues at positions "a" and "d" of a repeating heptad sequence. To determine the positional effects of interchain hydrophobic interactions on the stability of the coiled-coil, a single leucine residue in each chain at position "a" (9, 16, 23, 30) and "d" (5, 12, 19, 26, 33) was systematically replaced by an alanine. All these proteins formed two-stranded alpha-helical coiled-coils in benign conditions (0.05 M phosphate, 0.1 M KCl, pH 7). The stability of each mutant protein was determined by guanidine hydrochloride denaturation experiments, where the decrease in ellipticity at 220 nm was monitored by circular dichroism. The single alanine replacements of a leucine residue at hydrophobic positions a and/or d are all shown to destabilize the coiled-coil structure. The non-equivalent hydrophobic positions a and d make an equivalent contribution to protein stability along the majority of the coiled coil structure (positions 9-30). The small decrease in coiled-coil stability caused by Leu----Ala substitution at either ends of the coiled-coil suggested that the Leu-Leu hydrophobic interactions are less important at the ends of the coiled-coil and the ends of the coiled-coil are more flexible. Analysis of the difference between the ellipticity in benign buffer and in 50% trifluoroethanol (delta theta 220) and the slope term from a plot of the free energy of unfolding versus guanidine hydrochloride concentration also supported the conclusion that the leucine residues at the ends of the coiled-coil are much less buried than in the middle section of the coiled-coil. PMID- 1733964 TI - Amino-terminal processing of actins mutagenized at the Cys-1 residue. AB - Most actins examined to date undergo a unique posttranslational modification termed processing, catalyzed by the actin N-acetylaminopeptidase. Processing is the removal of acetylmethionine from the amino terminus in class I actins with Met-Asp(Glu) amino termini. For class II actins with Met-X-Asp(Glu) amino termini, processing is the removal of the second residue as an N-acetylamino acid. Other cytosolic proteins with these amino termini are not processed suggesting that the reaction may be specific for actins. In actin, X is usually cysteine. However, there are some class II actins in which this residue is other than cysteine, suggesting a broader substrate specificity for actin N acetylaminopeptidase than acetylmethionine or acetylcysteine. We constructed mutant actins in which this cysteine was replaced with serine, asparagine, glycine, aspartic acid, histidine, phenylalanine, and tyrosine and used these to determine the substrate specificity of rat liver actin N-acetylaminopeptidase in vitro. Amino-terminal acetylmethinonine was cleaved from adjacent aspartic acid, asparagine, or histidine, but not serine, glycine, phenylalanine, or tyrosine. Of the acetylated actin amino termini tested, only acetylmethionine and acetylcysteine were cleaved. Histidine was never N-acetylated and was not cleaved. When phenylalanine and tyrosine were adjacent to the initiator methionine, no initiator methionine was cleaved even though it was acetylated. These results suggest a narrow substrate specificity for the rat liver actin N acetylaminopeptidase. They also demonstrate that the adjacent residue can effect actin N-acetylaminopeptidase specificity. PMID- 1733965 TI - Protein-specific energy requirements for protein transport across or into thylakoid membranes. Two lumenal proteins are transported in the absence of ATP. AB - Cytosolically synthesized thylakoid proteins must be translocated across the chloroplast envelope membranes, traverse the stroma, and then be translocated into or across the thylakoid membrane. Protein transport across the envelope requires ATP hydrolysis but not electrical or proton gradients. The energy requirements for the thylakoid translocation step were studied here for the light harvesting chlorophyll a/b protein (LHCP), an integral membrane protein, and for several thylakoid lumen-resident proteins: plastocyanin and OE33, OE23, and OE17 (the 33-, 23-, and 17-kDa subunits of the oxygen-evolving complex, respectively). Dissipation of the thylakoid protonmotive force during an in organello protein import assay partially inhibited the thylakoid localization of LHCP and OE33, totally inhibited localization of OE23 and OE17, and had no effect on localization of plastocyanin. We used reconstitution assays for LHCP insertion and for OE23 and OE17 transport into isolated thylakoids to investigate the energy requirements in detail. The results indicated that LHCP insertion absolutely requires ATP hydrolysis and is enhanced by a transthylakoid delta pH and that transport of OE23 and OE17 is absolutely dependent upon a delta pH. Surprisingly, OE23 and OE17 transport occurred maximally in the complete absence of ATP. These results establish the thylakoid membrane as the only membrane system in which a delta pH can provide all of the energy required to translocate proteins across the bilayer. They also demonstrate that the energy requirements for integration into or translocation across the thylakoid membranes are protein specific. PMID- 1733966 TI - Interaction of two cis sites with the RNA replicase of the yeast L-A virus. AB - L-A is a 4.6-kilobase double-stranded RNA virus of Saccharomyces cerevisiae. The in vitro L-A replication reaction ((-)-strand synthesis) requires an internal site 400 bases from the 3' end in addition to the 3'-terminal 30 nucleotides of the L-A (+)-single-stranded RNA. Elimination of the internal site reduces the template activity 5-10-fold. Here we investigate how the internal site can stimulate the replication reaction which starts at the 3' end of the template. When these two sites are split into two distinct RNA molecules, the internal site can no longer stimulate replication (no trans-activation). However, establishment of an intermolecular hydrogen bonding between these RNAs restored the replication enhancing activity of the internal site. This result is consistent with a model wherein L-A's RNA polymerase interacts first with the internal site and then with the 3' end site by either looping or by a local dissociation-reassociation mechanism. These results, however, clearly eliminate anchored tracking and sliding models which require continuity of the RNA molecule between these two cis sites. PMID- 1733967 TI - EGF-R antisense RNA blocks expression of the epidermal growth factor receptor and suppresses the transforming phenotype of a human carcinoma cell line. AB - We have used an antisense approach to investigate the role of overexpression of the normal human epidermal growth factor (EGF) receptor in the transformed phenotype of KB cells, which are a tumor derived human cell line. Initial experiments performed in vitro, showed that antisense RNA complementary to the entire coding region (AS-FL) or to parts of the EGF-R mRNA (AS-3', AS-5', and AS K) effectively blocked translation of EGF-R mRNA. In addition, upon microinjection into KB cells, the in vitro synthesized antisense RNAs were able to inhibit transiently the synthesis of EGF-R. Inhibition was concentration dependent, both in vitro and in cells, and the most effective constructs were those complementary to the entire coding region (AS-FL) or to the 3'-coding end of the mRNA (AS-3'). Transfection of the same EGF-R antisense RNA constructs into the human epidermoid carcinoma KB cell line gave rise to several clones stably expressing elevated levels of antisense RNA and resulting in low residual levels of EGF receptor. The most reduced clones exhibited a totally restored serum dependent growth and were severely impaired in colony formation and growth in agar. In addition the severity of the phenotype was directly proportional to the residual amount of EGF-R expressed. We conclude that over-expression of normal EGF-R plays a direct primary role in the development of the transformed phenotype of this human cancer cell line. PMID- 1733968 TI - Choice of 3' cleavage/polyadenylation site in beta-tropomyosin RNA processing is differentiation-dependent in mouse BC3H1 muscle cells. AB - The rodent beta-tropomyosin (TM) gene produces either a 1.2-kilobase (kb) skeletal muscle beta-TM mRNA or a 1.1-kb fibroblast/smooth muscle TM-1 mRNA through tissue-specific alternative exon splicing and 3' cleavage/polyadenylation at two alternative poly(A) sites. beta-TM mRNA contains exon 6b, 9a, and the poly(A) site immediately following exon 9a, whereas TM-1 mRNA contains exon 6a, 9b, and the poly(A) site following exon 9b. We isolated a novel 2.1-kb beta-TM cDNA clone, pUTM, from a cDNA library of 2-day differentiated mouse BC3H1 muscle like cells. This cDNA contains the entire sequence of mature beta-TM mRNA with a normal but unused poly(A) site associated with exon 9a. Instead, 3' cleavage/polyadenylation of this cDNA occurred at the exon 9b-associated distal poly(A) site, resulting in the retention of a 1-kb intron and the TM-1 exon 9b. We identified a 2.3-kb functional mRNA, UTM RNA, corresponding to pUTM. UTM RNA appeared early during BC3H1 cell differentiation and gradually decreased as the beta-TM mRNA increased. UTM RNA was also detected in mouse C2C12 muscle cells and in skeletal muscle tissue isolated from mouse leg. Thus, in the processing of beta-TM gene transcripts, selection of alternative terminal exons and alternative poly(A) sites are not necessarily linked as they appear to be in other gene systems. PMID- 1733969 TI - Purification of the secretor-type beta-galactoside alpha 1----2 fucosyltransferase from human serum. AB - The secretor-type beta-galactoside alpha 1----2-fucosyltransferase from human serum was purified by hydrophobic chromatography on phenyl-Sepharose, ion exchange chromatography on sulfopropyl-Sepharose, and affinity chromatography on GDP-hexanolamine-Sepharose. Final purification of the enzyme was achieved by high pressure liquid chromatography gel filtration and resulted in a homogeneous protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the radiolabeled protein. The native enzyme appears as a molecule of apparent Mr 150,000 as determined by gel filtration high pressure liquid chromatography. The apparent Mr of the enzyme resolved in the presence of beta-mercaptoethanol by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was determined to be 50,000, indicating a multisubunit structure of the enzyme. Secretor-type alpha 1----2-fucosyltransferase is a glycoprotein as determined by WGA binding properties. A comparison of the Mr of the native blood group H gene encoded with the secretor-type beta-galactoside alpha 1----2-fucosyltransferases as well as comparison of subunit Mr for both enzymes suggests structural similarity. The alpha 1----2 linkage formed between alpha-L-fucose and terminal beta-D-galactose by the purified H- and secretor-type alpha 1----2 fucosyltransferases was determined by 1H NMR homonuclear cross-irradiation analysis of the oligosaccharide products. The substrate specificity and Km values calculated from the initial rate using various oligosaccharide acceptors showed that purified enzymes differ primarily in affinity for phenyl-beta-D galactopyranoside and GDP-fucose as well as type 1 (Gal beta 1----3GlcNAc), 2 (Gal beta 1----4GlcNAc), and 3 (Gal beta 1----3GalNAc) oligosaccharide acceptors. The secretor-type alpha 1----2-fucosyltransferase shows significantly lower affinity than the H enzyme for phenyl-beta-D-galactopyranoside and GDP-fucose as well as for type 2 oligosaccharide acceptors. On the contrary, type 1 and 3 oligosaccharide acceptors are preferentially utilized by the secretor-type enzyme as compared with the H enzyme. The enzymes also differ in several physicochemical properties, implying nonidentity of the two enzymes (Sarnesto, A., Kohlin, T., Thurin, J., and Blaszczyk-Thurin, M. (1990) J. Biol. Chem. 265, 15067-15075). PMID- 1733970 TI - Purification of the beta-N-acetylglucosaminide alpha 1----3-fucosyltransferase from human serum. AB - A beta-N-Acetylglucosaminide alpha 1----3-fucosyltransferase was purified from human serum by ammonium sulfate precipitation, hydrophobic chromatography on phenyl-Sepharose, ion-exchange chromatography on sulfopropyl-Sepharose, affinity chromatography on GDP-hexanolamine-Sepharose, and finally high pressure liquid chromatography gel filtration. Gel filtration chromatography of the native enzyme revealed a Mr of 45,000. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified protein also appeared as a single molecular species of Mr 45,000. In contrast to the multisubunit beta-galactoside alpha 1----2 fucosyltransferases with an apparent Mr of 150,000, present in human serum, the native beta-N-acetylglucosaminide alpha 1----3-fucosyltransferase is a monomer with a Mr of 45,000. The enzyme is glycosylated, as revealed by wheat germ agglutinin binding properties. The alpha 1----3 linkage formed by the enzyme between alpha-L-fucose and the penultimate beta-N-acetylglucosamine by the purified enzyme was confirmed by 1H NMR homonuclear cross-irradiation analysis of the oligosaccharide product. The specificity of the purified enzyme is restricted to type 2 structures, as revealed by its reactivity with different substrates and from the Km values calculated from the initial rate data using various oligosaccharide acceptors. The enzyme has the ability to utilize the N-acetyl beta-lactosamine determinant (Gal beta 1----4GlcNAc) and the sialylated (NeuAc alpha 2----3Gal beta 1----4GlcNAc) and fucosylated (Fuc alpha 1----2Gal beta 1--- 4GlcNAc) derivatives of N-acetyl-beta-lactosamine and thus is distinct from both the human Lewis gene-encoded enzyme and the alpha 1----3-fucosyltransferase of the myeloid cell type. PMID- 1733971 TI - Characterization of an abnormal fibrinogen Osaka V with the replacement of gamma arginine 375 by glycine. The lack of high affinity calcium binding to D-domains and the lack of protective effect of calcium on fibrinolysis. AB - Prolonged thrombin time was completely corrected by the addition of millimolar concentrations of calcium in a new abnormal fibrinogen, Osaka V. Analysis of lysyl endopeptidase digests of A alpha-, B beta-, or gamma-chains by high performance liquid chromatography, and the following amino acid sequence analysis of relevant peptides revealed that about 50% of the gamma-chain has a replacement of gamma-arginine 375 by glycine. When fibrinogen was digested with plasmin in the presence of millimolar concentration of calcium, the amount of fragment D1 was about 50% of the normal control, and the rest was further cleaved to fragment D2, D3, or D62 with an apparent Mr of 62,000. Plasmic digestion of cross-linked fibrin in the presence of calcium resulted in the appearance of an abnormal fragment with an apparent Mr of 123,000 as well as fragments D2, D3, and D62, concomitant with the decrease of D dimer. The gamma-remnant of the abnormal fragment proved to be a cross-linked complex of the normal D1 gamma-remnant and residues 374-406/411 of the abnormal gamma-chain. The number of high affinity Ca(2+)-binding sites for the normal fibrinogen and fibrinogen Osaka V obtained by equilibrium dialysis was 2.88 (about 3) and 1.85, respectively, and that for the abnormal molecules was calculated as 0.9 (about 1) from their relative amounts in the samples, suggesting the lack of two Ca(2+)-binding sites in the D-domains. These data suggest that the normal structure of the COOH-terminal portion of the gamma-chain including residue 375 is required for the full expression of high affinity calcium binding to D-domains, the ability to be protected by calcium against plasmic digestion, and fibrin polymerization. During these studies, we found that the NH2-terminal amino acid of the gamma-remnant in fragments D or D dimer which were obtained after prolonged digestion with plasmin is gamma-Met89. PMID- 1733972 TI - Accumulation of Golgi-processed secretory proteins in an organelle of high density upon reduction of ATP concentration in rat hepatocytes. AB - We have previously shown that when rat hepatocytes are incubated with 4 mM azide, which reduces the intracellular ATP concentration to about 30% of its normal level, secretory proteins are reversibly arrested within the cell. Analysis of haptoglobin after 150 min of azide incubation shows that its carbohydrates have been processed by Golgi enzymes (Persson, R., Ahlstrom, E., and Fries, E. (1988) J. Cell Biol. 107, 2503-2510). Here, we have further characterized the site of arrest. Subcellular fractionation by density gradient centrifugation showed that albumin and haptoglobin fractionated like a marker for the endoplasmic reticulum. Localization of albumin by immunoelectron microscopy showed, however, that it occurred in flattened cisternae and that the endoplasmic reticulum was devoid of the protein. A possible explanation for these results is that the azide treatment blocks transport through the Golgi complex, leading to an accumulation of secretory proteins in a pre- or early Golgi compartment of high density. This compartment could contain sufficient amounts of Golgi enzymes to carry out the observed carbohydrate processing upon prolonged incubation or possibly acquire them as an effect of the azide treatment. PMID- 1733973 TI - Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH. AB - Two new factors required for transcription of class II genes have been identified. These factors, TFIIH and TFIIJ, were required together with the previously described general factors (TFIIA, TFIIB, TFIID, TFIIE, and TFIIF) and RNA polymerase II for transcription of different class II genes. TFIIH was extensively purified, and the activity appeared to coelute with polypeptides of 33 and 95 kDa. The role of TFIIH and TFIIJ in preinitiation complex assembly was analyzed using mobility shift assays. It was found that TFIIH and TFIIJ association with the preinitiation complex was ordered and required the previous assembly of a preinitiation complex intermediate containing factors IID, IIB, IIF, IIE, and RNA polymerase II. A model for the ordered assembly of the general factors and RNA polymerase II is presented. PMID- 1733974 TI - Expression and polarized apical secretion in Madin-Darby canine kidney cells of a recombinant soluble form of neutral endopeptidase lacking the cytosolic and transmembrane domains. AB - Neutral endopeptidase-24.11 (NEP; EC 3.4.24.11) is an abundant metalloendopeptidase of the brush border membrane of kidney proximal tubules. We have recently shown that NEP is delivered directly to the apical domain of the plasma membrane when expressed in polarized Madin-Darby canine kidney (MDCK) cells in culture (Jalal, F., Lemay, G., Zollinger, M., Berteloot, A., Boileau, G., and Crine, P. (1991) J. Biol. Chem. 266, 19826-19832). Here, a soluble form of NEP consisting of the signal peptide of pro-opiomelanocortin fused in-frame with the ectodomain of NEP has been expressed in MDCK cells. Enzymatic assays performed on apical and basolateral culture media of MDCK cells grown on semi permeable supports indicated that the recombinant enzyme was predominantly released at the apical surface. In contrast, when the chimeric protein was expressed in NIH 3T3 cells or when pro-opiomelanocortin was expressed in MDCK cells, non-polarized secretion was observed into both the apical and basolateral compartments of the culture chamber. Our results suggest that the ectodomain of NEP is sufficient for directing the targeting of this protein to the apical membrane of polarized MDCK epithelial cells. PMID- 1733975 TI - Oxidative stress causes rapid membrane translocation and in vivo degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase. AB - We have studied the turnover of an abundant chloroplast protein, ribulose-1,5 bisphosphate carboxylase/oxygenase (Rbu-P2 carboxylase/oxygenase), in plants (Spirodela oligorrhiza and Triticum aestivum L.) and algae (Chlamydomonas reinhardtii and C. moewusii) induced to senesce under oxidative conditions. Rbu P2 carboxylase/oxygenase activity and stability in vivo were found to be highly susceptible to oxidative stress, resulting in intermolecular cross-linking of large subunits by disulfide bonds within the holoenzyme, rapid and specific translocation of the soluble enzyme complex to the chloroplast membranes, and finally protein degradation. The redox state of Cys-247 in Rbu-P2 carboxylase/oxygenase large subunit seems involved in the sensitivity of the holoenzyme to oxidative inactivation and cross-linking. However, this process did not drive membrane attachment or degradation of Rbu-P2 carboxylase/oxygenase in vivo. Translocation of oxidized Rbu-P2 carboxylase/oxygenase to chloroplast membranes may be a necessary step in its turnover, particularly during leaf senescence. Thus, processes that regulate the redox state of plant cells seem closely intertwined with cellular switches shifting the leaf from growth and maturation to senescence and death. PMID- 1733976 TI - Similar mechanisms for transcription initiation mediated through a TATA box or an initiator element. AB - Previous studies have identified several biochemical parameters that resolve promoter-specific transcription initiation by RNA polymerase II into distinct steps. We have employed these parameters to compare the mechanisms of initiation mediated through either a TATA box or a transcriptional initiator element. Time course experiments revealed that initiator-mediated transcription in a cell-free extract does not display the lag period typically found with TATA-mediated transcription. Titration experiments with increasing amounts of extract revealed further differences between TATA- and initiator-mediated transcription, again suggesting that different steps are rate-limiting. In contrast, experiments with the detergent Sarkosyl, which is believed to define later steps in the initiation process, revealed a striking degree of similarity between TATA- and initiator mediated transcription. Additional similarities were found using dinucleotide priming experiments, which are believed to measure the flexibility of initiation after RNA polymerase II is positioned over the transcription start site region. Taken together, these results suggest that the location of a preinitiation complex can be determined by core promoter recognition through either a TATA box or an initiator element. However, following these distinct template recognition events, the steps leading to initiation may be very similar and may proceed in a DNA sequence-independent manner. PMID- 1733977 TI - On Wolff's law of trabecular architecture. AB - Several studies suggest that the yield strain in cancellous bone may be uniformly distributed and isotropic. Yield strain was reported to be independent of textural anisotropy in bovine cancellous bone [Turner, J. biomech. Engng 111, 1-5 (1989)] and it is plausible that yield strain is isotropic in human cancellous bone as well. In this paper, it is hypothesized that uniform, isotropic strain represents a goal of cancellous bone adaptation, i.e. cancellous bone alters its structure to maintain uniform, isotropic peak strains. Therefore, textural anisotropy must exactly cancel the anisotropy of the peak principal stresses imposed upon cancellous bone. When evaluating the relationships between mechanical properties of cancellous bone and trabecular architecture, it was found that over 90% of the variance of yield strength can be explained by one term--rho 2H3 (where rho is apparent density and H is the normalized anisotropy (fabric) constant). Furthermore, this single term explains 70-78% of the variance in Young's modulus of cancellous bone. Based upon these findings, it was postulated that fabric adaptation goes as Hi/Hj = [ sigma i/sigma j[, where Hi and Hj are fabric eigenvalues in the i- and the j-direction and sigma i and sigma j are peak principal stresses. PMID- 1733978 TI - Micromechanics of the fibrosa and the ventricularis in aortic valve leaflets. AB - The elastic response of aortic valve cusps is a summation of its fibrous components. To investigate the micromechanical function of valve leaflet constituents, we separated the fibrosa and the ventricularis from fresh and glutaraldehyde-fixed leaflets and tested them individually. The ventricularis was stiffer circumferentially than radially (7.41 kPa vs 3.68 kPa, p less than 0.00001) and was more extensible radially (62.7% vs 21.8% strain to high modulus phase, p less than 0.00001). The fibrosa was also stiffer circumferentially than radially (13.02 kPa vs 4.65 kPa, p less than 0.0008), but had uniform extensibility. Glutaraldehyde fixation did not affect the circumferential elastic modulus of the fibrosa, but reduced its radial modulus from 4.65 kPa to 2.32 kPa (p less than 0.0078). The elastic modulus of the ventricularis remained unchanged. Fixation also reduced the extensibility of the ventricularis circumferentially (from 21.8% to 15.2% strain, p less than 0.018), but not radially, and increased the radial extensibility of the fibrosa from 27.7% to 46.1% (p less than 0.0048). These data show that while the ventricularis contains a large amount of elastin, the amount of radially oriented collagen is similar to that of the fibrosa. The fibrosa, by itself, has the same extensibility in both directions (about 23% strain), but can extend much more radially when connected to the rest of the leaflet because it is attached to the ventricularis in a highly folded configuration. The two layers therefore complement each other during aortic valve function, and become detrimentally altered by fixation in glutaraldehyde. PMID- 1733979 TI - Creep fracture in bones with different stiffnesses. AB - Creep fracture experiments were used to examine the differences in time to fracture of bones with very different Young's moduli (bovine bone and red deer antler) and the implications of these differences for the 'cumulative-damage' model of Caler and Carter [J. Biomechanics 22, 625-635 (1989)] for bone fracture. Using normalised stress as the explanatory variable, the slopes of the distributions agreed quite well with that of Caler and Carter for human bone. However, antler took far longer to fracture at any given normalised stress than did bovine bone. Using stress alone as the explanatory variable, the relationships within each bone type almost disappeared. Within any bone type strain is the important determinant of time to fracture, but less mineralised bone takes much longer to fracture at any given strain, or normalised stress, which seems not to be in accord with the cumulative-damage model. The rate of damage accumulation in lightly mineralised bone at high strains (greater than 1%) is much less than that occurring in more heavily mineralised bone. PMID- 1733980 TI - A new technique to study the mechanical properties of collagen lattices. AB - A new technique to study the mechanical properties of collagen lattices or dermal equivalents is described. With the help of the load-extension curve obtained with a uniaxial traction apparatus, a stiffness modulus varying from 0.06 to 1 MPa is calculated from the studied parameters (duration of culture, collagen and fibroblast concentration). The technique is presented as a new tool for testing the effect of pharmacological agents on the mechanical properties of the skin. PMID- 1733981 TI - Lumbar posterior ligament involvement during extremely heavy lifts estimated from fluoroscopic measurements. AB - The mechanical role of the lumbar posterior ligaments during lifting tasks remains controversial. This study was designed to assess the ligament and disc contribution in resisting trunk flexion moment during extremely heavy lifts performed by national class powerlifters. Direct measurements of lumbar vertebrae kinematics in sagittal plane were obtained from videofluoroscopy utilizing multiple digitizing, correction for optical distortions and digital filtering. Four experienced powerlifters executed three trials, resulting in about 72 mA s of total radiation exposure. In the first trial, joint angles were measured when subjects fully flexed their spines to a point where the passive tissues resisted the flexor moment creating myoelectric silence in the extensor musculature. Next, two conventional deadlift style lifts were executed with the barbell load ranging from 183.7 to 210.9 kg. Four vertebral corners were digitized at a sampling rate of 30 Hz. The relative intervertebral joint angles, distance between the ligament attachment points, shearing and compressive displacements were calculated from a rigid body motion approach. Analysis revealed that except for one trial of one subject, they accomplished their lifts with an amount of lumbar flexion between 1.5 and 13 degrees less than they demonstrated during full flexion. Resultant ligament lengths at the beginning of the lifts ranged from 56.1 to 99.8% of their lengths when the trunk was fully flexed. It was concluded that ligaments did not strain sufficiently to contribute substantial resistance to the trunk flexion moment, relegating this responsibility to the musculature. PMID- 1733982 TI - Human plantarflexor stiffness to multiple single-stretch trials. AB - The purpose of this investigation was to determine the influence of different stretch velocities, different rates of pre-stretch force development, and different pre-stretch muscle lengths on the intrinsic stiffness exhibited by the quasi-statically contracting active human plantarflexors during multiple single stretch trials at 20-60% of maximum isometric contraction. Subjects were positioned prone, with the knee flexed 1.57 rad(90 degrees), shank stabilized, and foot secured in a hard plastic orthotic. Slowly increasing isometric plantarflexion force was produced until the plantarflexors were stretched by a rapid 0.2 rad (12 degrees) dorsiflexion movement. Plantarflexion forces and ankle positions were determined during these stretches as well as during resting stretches when the muscle was inactive. Resting forces were subtracted from the active trials, forces converted to torques, and stiffnesses determined for the first 62 ms of the stretch. The slope of the stiffness vs pre-stretch torque relationship averaged 4.30 +/- 0.34 Nm rad-1 Nm-1. Little difference was found between stiffness determined through the single-stretch method and the results of previous studies employing different mechanical inputs. Differences in stiffnesses with different stretching velocities were caused by computational artifact rather than by differences in intrinsic muscular reaction. Faster rates of pre-stretch force increase prior to the stretch resulted in slightly lower stiffnesses. Different pre-stretch muscle lengths apparently did not result in different stiffnesses. The shape of the torque vs displacement curve was remarkably insensitive to the planned manipulations of the testing conditions, responding in a stereotypical manner. PMID- 1733983 TI - Three-dimensional knee joint loading during seated cycling. AB - The hypothesis which motivated the work reported in this article was that neglecting pure moments developed between the foot and pedal during cycling leads to a substantial error in computing axial and varus/valgus moments at the knee. To test this hypothesis, a mathematical procedure was developed for computing the three-dimensional knee loads using three-dimensional pedal forces and moments. In addition to data from a six-load-component pedal dynamometer, the model used pedal position and orientation and knee position in the frontal plane to determine the knee joint loads. Experimental data were collected from the right leg of 11 male subjects during steady-state cycling at 90 rpm and 225 W. The mean peak varus knee moment calculated was 15.3 N m and the mean peak valgus knee moment was 11.2 N m. Neglecting the pedal moment about the anterior/posterior axis resulted in an average absolute error of 2.6 N m and a maximum absolute error of 4.0 N m in the varus/valgus knee moment. The mean peak internal and external axial knee moments were 2.8 N m and 2.3 N m, respectively. The average and maximum absolute errors in the axial knee moment for not including the moment about an axis normal to the pedal were found to be 2.6 N m and 5.0 N m, respectively. The results strongly support the use of three-dimensional pedal loads in the computation of knee joint moments out of the sagittal plane. PMID- 1733984 TI - Visualization and quantification of the human blood flow by magnetic resonance imaging. AB - Magnetic Resonance Imaging (MRI) offers new possibilities for the visualization and the noninvasive quantification of the blood flow in human vessels. By the application of conventional gradient echo sequences with electrocardiographic gating on a 1.5 Tesla whole body MRI system the flow induced phase shifts in the ascending and the abdominal aorta are analyzed. The instantaneous two-dimensional velocity profiles and the instantaneous flow rates are determined in a series of subsequent images with high temporal resolution throughout the cardiac cycle. For the flow analysis in further vessels and for the analysis of more complex flow patterns, as they occur in bifurcations or stenoses, a new MR flow imaging technique called FAcE with extremely short echo times is introduced and the first results of flow examinations in a bifurcation phantom and in the carotid artery are presented. PMID- 1733985 TI - A new transducer for facet force measurement in the lumbar spine: benchmark and in vitro test results. AB - A new transducer capable of direct measurement of time-dependent loads in human lumbar facet joints was developed and tested. The transducer was comprised of a force-sensitive resistor (FSR) in series with a pressure-sensitive film. A wide range of experiments revealed the performance attributes and limitations of the FSR. The output signal of the FSR is actually sensitive to both force and area of contact independently. Therefore, a pressure-sensitive film was used to quantify the contact area. At least two transformation equations were calculated for each FSR corresponding to known contact areas. Each equation was a linearization of the log of the FSR output vs the log of the applied ramp loads. Coefficients of determination (CD) were calculated for small (21 mm2) and large (32 mm2) contact areas, and were found to exceed 0.900 for all data. The average of nine cycles was nearly linear for some FSRs (CD of 0.999). FSR output signal and contact area were recorded in cadaveric lumbar facets under ramp load. The appropriate transformation equation was determined by a linear interpolation between benchmark equations based on the contact area measured in vitro. Facet force measurements compared well with those of other researchers. The transducer was found to be quite easy to use. PMID- 1733986 TI - A theoretical model of the knee and ACL: theory and experimental verification. AB - A three-dimensional mathematical model of the human knee joint was developed to examine the role of single ligaments, such as an anterior cruciate ligament (ACL) graft in ACL reconstruction, on joint motion and tissue forces. The model is linear and valid for small motions about an equilibrium position. The knee joint is modeled as two rigid bodies (the femur and the tibia) interconnected by deformable structures, including the ACL or ACL graft, the cartilage layer, and the remainder of the knee tissues (modeled as a single element). The model was demonstrated for the equilibrium condition of the knee in extension with an anterior tibial force, causing anterior drawer and hyperextension. The knee stiffness matrix for this condition was measured for a human right knee in vitro. Predicted model response was compared with experimental observations. Qualitative agreement was found between model and experiment, validating the model and its assumptions. The model was then used to predict the change in graft and cartilage forces and joint motion of the knee due to an increment of load in the normal joint both after ACL removal and with various altered states simulating ACL reconstructions. Results illustrate the interdependence between loads in the ACL graft, other knee structures, and contact force. Stiffer grafts and smaller maximum unloaded length of the ligament lead to higher graft and contact forces. Changes in cartilage stiffness alter load sharing between ACL graft and other joint tissues. PMID- 1733987 TI - A model of pulsatile flow in a uniform deformable vessel. AB - Simulations of blood flow in natural and artificial conduits usually require large computers for numerical solution of the Navier-Stokes equations. Often, physical insight into the fluid dynamics is lost when the solution is purely numerical. An alternative to solving the most general form of the Navier-Stokes equations is described here, wherein a functional form of the solution is assumed in order to simplify the required computations. The assumed forms for the axial pressure gradient and velocity profile are chosen such that conservation of mass is satisfied for fully established pulsatile flow in a straight, deformable vessel. The resulting equations are cast in finite-difference form and solved explicitly. Results for the limiting cases of rigid wall and zero applied pressure are found to be in good agreement with analytical solutions. Comparison with the experimental results of Klanchar et al. [Circ. Res. 66, 1624-1635 (1990]) also shows good agreement. Application of the model to realistic physiological parameter values provides insight as to the influence of the pulsatile nature of the flow field on wall shear development in the presence of a moving wall boundary. Specifically, the model illustrates the dependence of flow rate and shear rate on the amplitude of the vessel wall motion and the phase difference between the applied pressure difference and the oscillations of the vessel radius. The present model can serve as a useful tool for experimentalists interested in quantifying the magnitude and character of velocity profiles and shearing forces in natural and artificial biologic conduits. PMID- 1733988 TI - Heel-off perturbation during gait initiation: biomechanical analysis using triaxial accelerometry and a force plate. AB - This study analyzes the movements of the hips, shoulders and of the body center of gravity before and at heel-off, when step execution begins to initiate gait from an upright posture. The heel-off movement was considered as a dynamic perturbation induced by the stepping movement. The experimental paradigm used for studying this perturbation was the single-step movement, in which the initial posture and voluntary movements are identical to those of gait initiation. Data were collected from accelerometer recordings of the triaxial accelerations at the joints of the upper part of the body, and by calculating the triaxial accelerations of the center of gravity using force plate measurements. The resultant vectors were used to establish and compare the magnitude and direction of the accelerations at different joints, and from them, the roles of the pelvis and the scapular girdles with respect to the objectives of the gait movement. PMID- 1733989 TI - Geometry parameters for musculoskeletal modelling of the shoulder system. AB - A dynamical finite-element model of the shoulder mechanism consisting of thorax, clavicula, scapula and humerus is outlined. The parameters needed for the model are obtained in a cadaver experiment consisting of both shoulders of seven cadavers. In this paper, in particular, the derivation of geometry parameters from the measurement data is described. The results for one cadaver are presented as a typical example. Morphological structures are modelled as geometrical forms. Parameters describing this form are estimated from 3-D position coordinates of a large number of datapoints on the morphological structure, using a least-squares criterion. Muscle and ligament attachments are represented as a plane or as a (curved) line. Muscle paths are determined by a geometrical form of the bony contour around which the muscle is wrapped. Muscle architecture is determined by the distribution of muscle bundles over the attachment area, mapping the distribution of the origin to the insertion. Joint rotation centers are derived from articular surfaces. Hence, muscle moment arms can be calculated. The result of this study is a set of parameters for each cadaver, describing very precisely the geometry of the shoulder mechanism. This set allows positioning of muscle force vectors a posteriori, and recalculation of position coordinates and moment arms for any position of the shoulder. PMID- 1733990 TI - Mass, center of mass, and moment of inertia estimates for infant limb segments. AB - To quantify limb dynamics, accurate estimates are needed of anthropometric inertia parameters (mass, center-of-mass location, and moments of inertia). These estimates, however, are not available for human infants; therefore, the movement dynamics of infants have not been studied extensively. Here, regression equations for the masses, center-of-mass locations, and transverse moments of inertia of upper and lower limb segments (upper arm, forearm, and hand; thigh, leg, and foot) of 0.04 to 1.50 yr old infants are provided. A mathematical model of the human body was used to determine the anthropometric inertia parameters for upper limbs in 44 infants and for lower limbs in 70 infants. Stepwise linear regressions were used to fit the distributions of the anthropometric inertia parameters. The regression equations accounted for significant amounts of the variance (64-98%), and the R2-values compared favorably when our equations were cross-validated. Consequently, these regression equations can provide, for infants of similar ages, reasonable estimates of upper and lower limb anthropometric inertia parameters, suitable for equations of motion in the analysis of limb dynamics in human infants. PMID- 1733991 TI - A kinematic model of the human hand to evaluate its prehensile capabilities. AB - A kinematic model has been developed for simulation and prediction of the prehensile capabilities of the human hand. The kinematic skeleton of the hand is characterized by ideal joints and simple segments. Finger-joint angulation is characterized by yaw (abduction-adduction), pitch (flexion-extension) and roll (axial rotation) angles. The model is based on an algorithm that determines contact between two ellipsoids, which are used to approximate the geometry of the cutaneous surface of the hand segments. The model predicts the hand posture (joint angles) for power grasp of ellipsoidal objects by 'wrapping' the fingers around the object. Algorithms for two grip types are included: (1) a transverse volar grasp, which has the thumb abducted for added power; and (2) a diagonal volar grasp, which has the thumb adducted for an element of precision. Coefficients for estimating anthropometric parameters from hand length and breadth are incorporated in the model. Graphics procedures are included for visual display of the model. In an effort to validate the predictive capabilities of the model, joint angles were measured on six subjects grasping circular cylinders of various diameters and these measured joint angles were compared with angles predicted by the model. Sensitivity of the model to the various input parameters was also determined. On an average, the model predicted joint flexion angles that were 5.3% or 2.8 degrees +/- 12.2 degrees larger than the measured angles. Good agreement was found for the MCP and PIP joints, but results for DIP were more variable because of its dependence on the predictions for the proximal joints. PMID- 1733992 TI - Mechanical properties of the canine patellar tendon: some correlations with age and the content of collagen. AB - Portions of the patellar tendon (PT) are currently used for autogenous and allogeneic reconstruction of a torn or damaged anterior cruciate ligament (ACL). Age-related changes in the mechanical properties of the PT may influence its use in this reconstruction procedure. Age-dependent changes in the PT were determined in the dog, which is often used to experimentally study this reconstruction. Tensile failure experiments were performed at 100% s-1 on patella-patellar tendon tibia preparations from dogs aged 0.5-15 yr. The contents of collagen soluble and insoluble in pepsin were also measured at each age. Fifty-nine percent (16/27) of the preparations failed by avulsion at the patella, but neither the failure load nor the mode of failure were a function of age. Failure load and energy were higher for tendon substance failures compared to avulsions of bone from the patella. While a positive, linear correlation was measured between tensile modulus of the PT and age, the slope of regression was not significantly different from zero. The content of total collagen in the PT decreased significantly with age. The content of collagen insoluble in pepsin, however, increased with age and positively correlated with tensile modulus of the tendon. These results are different from those reported for the canine CCL, by others, which degenerates with age. Age-related changes in the mechanical properties of the canine PT are qualitatively similar to earlier, limited data on human patellar tendons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733993 TI - Application and validation of a three-dimensional mathematical model of the human masticatory system in vivo. AB - A previously described three-dimensional mathematical model of the human masticatory system, predicting maximum possible bite forces in all directions and the recruitment patterns of the masticatory muscles necessary to generate these forces, was validated in in vivo experiments. The morphological input parameters to the model for individual subjects were collected using MRI scanning of the jaw system. Experimental measurements included recording of maximum voluntary bite force (magnitude and direction) and surface EMG from the temporalis and masseter muscles. For bite forces with an angle of 0, 10 and 20 degrees relative to the normal to the occlusal plane the predicted maximum possible bite forces were between 0.9 and 1.2 times the measured ones and the average ratio of measured to predicted maximum bite force was close to unity. The average measured and predicted muscle recruitment patterns showed no striking differences. Nevertheless, some systematic differences, dependent on the bite force direction, were found between the predicted and the measured maximum possible bite forces. In a second series of simulations the influence of the direction of the joint reaction forces on these errors was studied. The results suggest that they were caused primarily by an improper determination of the joint force directions. PMID- 1733994 TI - Towards a model for force predictions in the human shoulder. AB - In this paper the concept of a three-dimensional biomechanical model of the human shoulder is introduced. This model is used to analyze static load sharing between the muscles, the bones and the ligaments. The model consists of all shoulder structures, which means that different positions and different load situations may be analyzed using the same model. Solutions can be found for the complete range of shoulder motion. However, this article focuses only on elevation in the scapular plane and on forces in structures attached to the humerus. The intention is to expand the model in future studies to also involve the forces acting on the other shoulder bones: the scapula and the clavicle. The musculoskeletal forces in the shoulder complex are predicted utilizing the optimization technique with the sum of squared muscle stresses as an objective function. Numerical results predict that among the muscles crossing the glenohumeral joint parts of the deltoideus, the infraspinatus, the supraspinatus, the subscapularis, the pectoralis major, the coracobrachialis and the biceps are the muscles most activated during this sort of abduction. Muscle-force levels reached values of 150 N when the hand load was 1 kg. The results from the model seem to be qualitatively accurate, but it is concluded that in the future development of the model the direction of the contact force in the glenohumeral joint must be constrained. PMID- 1733995 TI - Knee muscle moment arms from MRI and from tendon travel. AB - We tested magnetic resonance imaging (MRI) as a means to collect geometric data for moment arm estimation. A knee specimen in five successive flexion postures was scanned by MRI, while simultaneously tendon positions of loaded muscles were measured (long head of biceps femoris, lateral and medial gastrocnemius, gracilis, rectus femoris, sartorius, semimembranosus, semitendinosus, and tensor fasciae latae). Discrete rotation centres were derived from MRI pictures. Moment arms were estimated as the distances from these centres to the tendons. The ratio of tendon travel over the increment of joint angulation was the alternative, more reliable estimate of the moment arm. An important principal shortcoming of MRI is the impossibility of accounting for force distribution in taut tissue. As a consequence, for some muscles, considerable inaccuracies in moment arm estimation are found in a relatively small range of joint angulation (up to about 30% for the rectus femoris and semimembranosus). For the tensor fasciae latae, the moment arm cannot be estimated by MRI, while the estimate by tendon travel is unreliable owing to the deformability and attachments of the fascia lata. PMID- 1733996 TI - On the role of biarticular muscles in human jumping. PMID- 1733997 TI - Evaluation of the lymph flow with lymphoscintigraphy after rotationplasty for the treatment of bone tumors. AB - We studied the cases of eleven patients in whom a rotationplasty had been done after wide resection of the distal part of the femur. All patients had had a malignant tumor of bone, but none had the complication of edema or leakage of lymph after the rotationplasty. We made lymphoscintiscans soon after the operation in four patients and weeks or months later in all eleven patients. There was a delay in the flow of lymph in three of the four patients who were examined lymphoscintigraphically soon after the operation and there was obstruction of flow in the fourth patient, but there was evidence of a decreased rate of flow in only two of the eleven patients at the time of the later examination. PMID- 1733998 TI - Intramedullary nailing of femoral shaft fractures. Part III: Long-term effects of static interlocking fixation. AB - The results of treatment of fractures of the femoral shaft with static interlocking nailing were reviewed retrospectively to determine the clinical importance of any stress-riser or stress-shielding properties of the nail. These properties, if relevant, would have been manifested by refracture of the femur, either through a hole used for a locking screw or through the original site of fracture after extraction of the device. Two hundred and fourteen fractures that had been treated with static interlocking nailing and that had healed without conversion to dynamic intramedullary fixation were divided into two groups. In Group I, which comprised 111 fractures, the static interlocking-fixation device was retained and in Group II, which comprised 103 fractures, the static interlocking-fixation device was removed during one operative procedure at an average of fourteen months after the injury. The average duration of follow-up was thirty months from the time of the original fixation in both groups. All patients in Group II were followed for a minimum of six months after removal of the nail. No femur in Group I, in which the static interlocked nail remained in situ, refractured. No femur in either group fractured through the proximal or the distal holes used for the locking screws. No locking screws or nails broke. One patient (1 per cent) in Group II had a refracture of the femoral shaft through the site of the original fracture six weeks after removal of the nail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1733999 TI - Survival of cells after intra-articular transplantation of fresh allografts of the patellar and anterior cruciate ligaments. DNA-probe analysis in a goat model. AB - The fate of donor cells in fresh allografts of the patellar and anterior cruciate ligaments was assessed after transplantation of the allografts as substitutes for the anterior cruciate ligament in goats. DNA-probe analysis was used to distinguish between the DNA of individual goats. Donor DNA was completely replaced by recipient DNA in both the transplanted patellar and anterior cruciate ligaments within a four-week period. Simultaneous full-thickness skin transplants in the same animals were not rejected during the interval of rapid loss of donor DNA from the allografts. The absence of rejection of the skin grafts at the one week interval suggests that no pre-existing antibody associated with an immune reaction was responsible for the rapid loss of DNA in the allografts. PMID- 1734000 TI - The weight-bearing abduction brace for the treatment of Legg-Perthes disease. AB - We reviewed the cases of thirty-one patients (thirty-four hips) who had had severe Legg-Perthes disease (Catterall group III, five hips and group IV, twenty nine hips) and had been treated with a weight-bearing abduction orthosis, to determine the effectiveness of the brace. The mean age of the patients when they were first seen was six years (range, three to twelve years). The mean duration of follow-up was seven years (range, two to thirteen years). At the most recent follow-up, all hips were rated with the method of Mose and the classification of Stulberg et al. According to the criteria of Mose, no hip had a good result, twelve (35 per cent) had a fair result, and twenty-two (65 per cent) had a poor result. On the basis of the classification of Stulberg et al., there were fourteen (41 per cent) class-II results, eighteen (53 per cent) class-III and IV results, and two (6 per cent) class-V results. Although containment is the most widely accepted principle of treatment for patients who have Legg-Perthes disease, and the Atlanta Scottish Rite-type orthosis is the most commonly used orthosis for this condition, there are few clinical data supporting the effectiveness of this device. On the basis of our results, we do not recommend the use of a weight-bearing abduction brace for the treatment of severely involved hips. PMID- 1734001 TI - Repair of hallux valgus with a distal soft-tissue procedure and proximal metatarsal osteotomy. A long-term follow-up. AB - We retrospectively reviewed the results for seventy-five patients (109 feet) in whom a hallux valgus deformity had been corrected with the release of the distal soft tissues, excision of the medial eminence, plication of the medial part of the capsule, and proximal crescentic osteotomy of the first metatarsal. The patients were followed for an average of thirty-four months (range, twenty-four to fifty-six months). The preoperative hallux valgus angle averaged 31 degrees, and the postoperative angle averaged 9 degrees. The preoperative intermetatarsal angle averaged 14 degrees and the postoperative angle, 6 degrees. Ninety-three per cent of the patients were satisfied with the result of the procedure. They stated that, given the same circumstances, they would have the operation again. The most common complication was hallux varus, which occurred in thirteen feet (nine patients). The other complications included recurrence of the hallux valgus in two feet, pain under a fibular sesamoid in one foot, and a tailor's bunion that was unrelated to the operation in one foot. Only five of forty-eight feet that had had a symptomatic plantar keratosis beneath the second metatarsal head preoperatively remained symptomatic postoperatively. PMID- 1734002 TI - Isolated avulsion of the popliteus tendon: operative repair. A report of two cases. PMID- 1734003 TI - Fracture of the middle third of the clavicle and dislocation of the acromioclavicular joint. A report of four cases. PMID- 1734004 TI - Hypoglossal nerve palsy after arthroscopy of the shoulder and open operation with the patient in the beach-chair position. A case report. PMID- 1734005 TI - The treatment of injuries of the anterior cruciate ligament. PMID- 1734006 TI - Osteoarticular allografts for reconstruction in the proximal part of the humerus after excision of a musculoskeletal tumor. PMID- 1734007 TI - Evidence for a humoral mechanism for enhanced osteogenesis after head injury. PMID- 1734008 TI - Use of a knee-brace for control of tibial translation and rotation. A comparison, in cadavera, of available models. PMID- 1734009 TI - The Scottish Rite abduction orthosis for the treatment of Legg-Perthes disease. A radiographic analysis. AB - We evaluated a consecutive series of thirty-four patients who had had Legg Perthes disease to determine the results of treatment with the Scottish Rite weight-bearing abduction orthosis. All patients had been older than six years at the time of the onset of the symptoms, had been in the fragmentation phase of the disease when they were first seen, and had had Catterall group-III or IV involvement. Although comparison of this series with those reported previously is difficult due to the variability of the presentation of data in the literature, this orthosis does not appear to offer an advantage compared with other methods of management, or with no treatment, for patients such as those whom we studied. PMID- 1734010 TI - Cervical stability after foraminotomy. A biomechanical in vitro analysis. AB - Laminectomy or facetectomy of the cervical spine, or both, may be needed for decompression of the spinal cord or of the nerve-roots. Acute stability of the cervical spine was tested after laminectomy and progressive staged foraminotomies in an in vitro model. Twelve cervical spines from human cadavera were used in the experiment. Biomechanical testing included the application of an axial load, the application of a flexion and extension moment, and the application of a torsional moment. Each specimen was tested intact, after laminectomy of the fifth cervical vertebra, and after progressive foraminotomy of the sixth cervical root. Foraminotomy was performed by resection of 25, 50, 75, and 100 per cent of the facet joint and capsule. Torsional stiffness decreased dramatically when more than 50 per cent of the facet had been resected. Statistically equivalent subsets were the intact specimen, laminectomy, 25 per cent facetectomy, and 50 per cent facetectomy in one subset, and 75 and 100 per cent facetectomy in the least-stiff subset. Flexion-moment testing showed that the posterior strain did not differ among three groups: the intact specimens, those that had been treated with laminectomy, and those that had been treated with a 25 per cent facetectomy. The 50 per cent facetectomy resulted in a 2.5 per cent increase in posterior strain, and the 75 or 100 per cent facetectomy, in a 25 per cent increase in posterior strain compared with the intact specimen. Segmental hypermobility of the cervical spine results if a foraminotomy involves resection of more than 50 per cent of the facet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734011 TI - Epithelioid sarcoma in the upper extremity. AB - Eighteen patients who had epithelioid sarcoma in the upper extremity were divided into two groups on the basis of treatment: marginal resection of the tumor or wide or radical resection of the tumor. Historical, demographic, histological, and staging data were recorded and were correlated with the type of treatment and the outcome. Marginal resection (excision through the reactive zone or pseudocapsule surrounding the tumor, with confirmation of a negative margin by a pathologist), with or without adjuvant therapy, led to a dismal outcome in patients who had been treated in this manner initially or secondarily (fifteen failures after seventeen procedures). Disease-free survival at ten years was significantly improved when wide resection (intracompartmental en bloc excision with a cuff of normal tissue of more than three centimeters) or radical resection was either the initial or the secondary treatment; success then was noted in nine of thirteen operations. Of twelve patients in whom a marginal resection had been done initially, three had had a recurrence, three had had a metastasis, and five had died, at a mean follow-up of seven years (range, twenty-seven months to sixteen years). At a mean follow-up of six years (range, two to fifteen years), only one of five patients in whom a secondary lesion had been treated with marginal resection was free of disease. Of the six patients who had been treated with wide or radical resection initially, none had died, one had had a recurrence, and one had had a metastasis, at a mean follow-up of seven years (range, twenty-two months to fourteen years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734012 TI - Anatomy and relationships of the suprascapular nerve: anatomical constraints to mobilization of the supraspinatus and infraspinatus muscles in the management of massive rotator-cuff tears. AB - Thirty-one shoulders in eighteen cadavera were dissected to allow study of the neurovascular anatomy of the rotator cuff and to help determine the limits of mobilization of the cuff for the repair of chronic massive retracted tears. The dissection demonstrated the diameter, length, and relationships of the suprascapular nerve and its branches and made clear the dangers of extensive mobilization and advancement of the supraspinatus and infraspinatus muscles. The suprascapular nerve ran an oblique course across the supraspinatus fossa, was relatively fixed on the floor of the fossa, and was tethered underneath the transverse scapular ligament. In twenty-six (84 per cent) of the thirty-one shoulders, there were no more than two motor branches to the supraspinatus muscle, and the first was always the larger of the two. In twenty-six (84 per cent) of the thirty-one shoulders, the first motor branch originated underneath the transverse scapular ligament or just distal to it. In one shoulder (3 per cent), the first motor branch passed over the ligament. The average distance from the origin of the long tendon of the biceps to the motor branches of the supraspinatus was three centimeters. In fifteen (48 per cent) of the thirty-one shoulders, the infraspinatus muscle had three or four motor branches of the same size. The average distance from the posterior rim of the glenoid to the motor branches of the infraspinatus muscle was two centimeters. The motor branches to the supraspinatus muscle were fewer, usually smaller, and significantly shorter than those to the infraspinatus muscle. The standard anterosuperior approach allowed only one centimeter of lateral advancement of either tendon and limited the ability of the surgeon to dissect safely beyond the neurovascular pedicle. The advancement technique of Debeyre et al., or a modification of that technique, permitted lateral advancement of each muscle of as much as three centimeters and was limited by tension in the motor branches of the suprascapular nerve. In some situations, the safe limit of advancement may be even less. We concluded that lateral advancement of the rotator cuff is limited anatomically and may place the neurovascular structures at risk. PMID- 1734013 TI - Anatomy, histology, and vascularity of the glenoid labrum. An anatomical study. AB - We studied the gross, histological, and vascular anatomy of the glenoid labrum in twenty-three fresh-frozen shoulders from cadavera to demonstrate its cross sectional anatomy, its microvascularity, and its attachments. The superior and anterosuperior portions of the labrum are loosely attached to the glenoid, and the macro-anatomy of those portions is similar to that of the meniscus of the knee. The superior portion of the labrum also consistently inserts directly into the biceps tendon, while its inferior portion is firmly attached to the glenoid rim and appears as a fibrous, immobile extension of the articular cartilage. The arteries supplying the periphery of the glenoid labrum come from the suprascapular, circumflex scapular, and posterior circumflex humeral arteries. In general, the superior and anterosuperior parts of the labrum have less vascularity than do the posterosuperior and inferior parts, and the vascularity is limited to the periphery of the labrum. Vessels supplying the labrum originate from either capsular or periosteal vessels and not from the underlying bone. PMID- 1734014 TI - The role of the rotator interval capsule in passive motion and stability of the shoulder. AB - The purpose of this study was to characterize the role of the capsule in the interval between the supraspinatus and subscapularis tendons with respect to glenohumeral motion, translation, and stability. We used a six-degrees-of-freedom position-sensor and a six-degrees-of-freedom force and torque-transducer to determine the glenohumoral rotations and translations that resulted from applied loads in eight cadaver shoulders. The range of motion of each specimen was measured with the capsule in the rotator interval in a normal state, after the capsule had been sectioned, and after it had been imbricated. Operative alteration of this capsular interval was found to affect flexion, extension, external rotation, and adduction of the humerus with respect to the scapula. Modification of this portion of the capsule also affected obligate anterior translation of the humeral head on the glenoid during flexion. Limitation of motion and obligate translation were increased by operative imbrication and diminished by sectioning of the rotator interval capsule. Passive stability of the glenohumeral joint was evaluated with the use of anterior, posterior, and inferior stress tests. Instability and occasional frank dislocation of the glenohumeral joint occurred inferiorly and posteriorly after section of the rotator interval capsule. Imbrication of this part of the capsule increased the resistance to inferior and posterior translation. PMID- 1734015 TI - Medial instability of the elbow in throwing athletes. Treatment by repair or reconstruction of the ulnar collateral ligament. AB - From September 1974 to December 1987, seventy-one patients were operated on for valgus instability of the elbow. The average length of follow-up of sixty-eight patients (seventy operations) was 6.3 years (range, two to fifteen years). At the operation, a torn or incompetent ulnar collateral ligament was found. Fourteen patients had a direct repair of the ligament, and fifty-six had a reconstruction of the ligament using a free tendon graft. The result was excellent or good in ten patients in the repair group and in forty-five (80 per cent) in the reconstruction group. Seven of the fourteen patients who had a direct repair returned to the previous level of participation in their sport. Of the fifty-six who had a reconstruction, thirty-eight (68 per cent) returned to the previous level of participation. Twelve of the sixteen major-league baseball players who had a reconstruction as the primary operation (no previous operation on the elbow) were able to return to playing major-league baseball, and two of the seven major-league players who had a direct repair returned to playing major-league baseball. Previous operations on the elbow decreased the chance of returning to the previous level of sports participation (p = 0.04). Fifteen patients had postoperative ulnar neuropathy. This was transient in six patients, only one of whom was unable to return to the previous level of sport. The other nine patients had an additional operation for the neuropathy; four were able to return to the previous level of sport. PMID- 1734016 TI - Arthroscopy of the elbow. Diagnostic and therapeutic benefits and hazards. AB - We analyzed the results of seventy-one arthroscopies of the elbow in seventy patients who had been followed for an average of thirty-four months, in order to evaluate the risks and benefits of the procedure. Thirty-four arthroscopies were done for diagnostic purposes, fifteen were done for treatment, and twenty-two were done for both diagnosis and treatment. Overall, fifty-one (73 per cent) of the seventy patients benefited in some way. There were diagnostic benefits in thirty-six (64 per cent) of the fifty-six elbows in which diagnosis was an indication for the procedure, and there were therapeutic benefits in thirty (70 per cent) of the forty-three elbows in which treatment was intended or was performed although not planned. The procedure was of benefit in only eighteen (75 per cent) of the twenty-four elbows that had loose bodies, but it was successful in all elbows in which the loose bodies were not secondary to some other condition, including arthrosis. The procedure was also successful in all four elbows in which the loose bodies had been due to osteochondritis dissecans. In twelve (80 per cent) of the fifteen patients who had debridement (removal of flaps or loose fragments of articular cartilage) and in one of the two in whom a synovectomy had been performed, the treatment was successful. Seven (10 per cent) of the seventy patients had complications, none of which were major. Three patients (4 per cent) had a transient radial-nerve palsy after intra-articular injection of local anesthetic; four others had persistent drainage and negative cultures, but the drainage resolved with antibiotic therapy. In one of the four patients, a permanent flexion contracture of 15 degrees developed, and 10 degrees of flexion was lost. PMID- 1734017 TI - Capitellocondylar total elbow replacement. A long-term follow-up study. AB - Fifty-one capitellocondylar elbow replacements were inserted in forty-one patients between 1976 and 1986. Thirty-nine patients had rheumatoid arthritis and two had traumatic osteoarthrosis. The average age of the patients at the time of the operation was fifty-six years (range, twenty-one to seventy-seven years). Thirty-one patients who had thirty-nine retained elbow prostheses had an average length of follow-up of 6.5 years (range, two to thirteen years). Flexion improved an average of 20 degrees; extension, 4 degrees; pronation, 22 degrees; and supination, 36 degrees. Relief of pain was complete in 85 per cent of the thirty nine elbows, and in 15 per cent there was only mild pain. Noteworthy postoperative complications in the original fifty-one elbows included infection in four elbows (8 per cent), dislocation in three (6 per cent), and ulnar neuropathy in sixteen (31 per cent). Three elbows were revised: one for a humeral fracture, one for recurrent dislocation, and one for aseptic loosening. Aseptic loosening was evident on radiographs of two elbows; one patient was completely asymptomatic, and one had mild pain with deformity. The Souter zonal radiographic assessment system for identification of radiolucencies at the bone-cement interface was utilized; there was no significant difference in radiolucencies between ulnar components backed with metal and those that were not backed with metal. Kaplan-Meier cumulative survivorship analysis demonstrated that a functional prosthesis was retained in 88 per cent of the elbows at 1.4 years postoperatively and in 83 per cent at 5.5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734018 TI - Induction of proliferation or hypertrophy of chondrocytes in serum-free culture: the role of insulin-like growth factor-I, insulin, or thyroxine. AB - In bone forming cartilage in vivo, cells undergo terminal differentiation, whereas most of the cells in normal articular cartilage do not. Chondrocyte hypertrophy can be induced also in vitro by diffusible signals. We have identified growth factors or hormones acting individually on 17-d chick embryo sternal chondrocytes cultured in agarose gels under strictly serum-free conditions. Insulin-like growth factor I or insulin triggered the first steps of chondrocyte maturation, i.e., cell proliferation and increased matrix deposition while the chondrocytic phenotype was maintained. However, cells did not progress to the hypertrophic stage. Proliferation and stimulated collagen production was preceded by a lag period, indicating that synthesis of other components was required before cells became responsive to insulin-like growth factor I or insulin. Very small amounts of FBS exerted effects similar to those of insulin like growth factor I or insulin. However, FBS could act directly and elicited hypertrophy when constituting greater than 1% of the culture media. Basic FGF has been claimed to be the most potent chondrocyte mitogen, but had negligible effects under serum-free conditions. The same is true for PDGF, a major serum mitogen. Under the direction of thyroxine, cells did not proliferate but became typical hypertrophic chondrocytes, extensively synthesizing collagen X and alkaline phosphatase. PMID- 1734019 TI - Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. AB - The influence of extracellular matrix configuration on the tissue-specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix. PMID- 1734020 TI - Deletion of the regulatory domain of protein kinase C alpha exposes regions in the hinge and catalytic domains that mediate nuclear targeting. AB - Members of the protein kinase C (PKC) family are characterized by an NH2-terminal regulatory domain containing binding sites for calcium, phosphatidylserine, and diacylglycerol (or tumor-promoting phorbol esters), a small central hinge region and a COOH-terminal catalytic domain. We have constructed fusion proteins in which the regulatory domain of PKC alpha was removed and replaced by a 19-amino acid leader sequence containing a myristoylation consensus or by the same sequence in which the amino-terminal glycine was changed to alanine to prevent myristoylation. The goal was to generate constitutively active mutants of PKC that were either membrane bound, due to their myristoylation, or cytoplasmic. Western blotting of fractions from COS cells transfected with plasmids encoding wild-type and mutant proteins revealed that PKC alpha resided entirely in a Triton X-100 soluble (TS) fraction, whereas both the myristoylated and nonmyristoylated mutants were associated primarily with the nuclear envelope fraction. A similar mutant that lacked the 19 amino acid leader sequence was also found almost entirely in the nuclear envelope, as was a truncation mutant containing only the regulatory domain, hinge region, and a small portion of the catalytic domain. However, an additional truncation mutant consisting of only the regulatory domain plus the first one-third of the hinge region was almost entirely in the TS fraction. A nonmyristoylated fusion protein containing only the catalytic domain was also found in the nuclear envelope. Immunostaining of cells transfected with these constructs revealed that both the myristoylated and nonmyristoylated mutants were localized in nuclei, whereas wild-type PKC alpha was primarily cytoplasmic and perinuclear. Phorbol dibutyrate treatment of PKC alpha-transfected cells resulted in increased perinuclear and nuclear staining. The results are consistent with a model in which activation of PKC, by phorbol esters or by deletion of the regulatory domain, exposes regions in the hinge and catalytic domains that interact with a PKC "receptor" present in the nuclear envelope, and may explain the ability of wild-type PKC to be translocated to the nucleus under certain conditions. PMID- 1734021 TI - Fc receptor endocytosis is controlled by a cytoplasmic domain determinant that actively prevents coated pit localization. AB - Macrophages and B-lymphocytes express two major isoforms of Fc receptor (FcRII-B2 and FcRII-B1) that exhibit distinct capacities for endocytosis. This difference in function reflects the presence of an in-frame insertion of 47 amino acids in the cytoplasmic domain of the lymphocyte isoform (FcRII-B1) due to alternative mRNA splicing. By expressing wild type and mutant FcRII cDNAs in fibroblasts, we have now examined the mechanism by which the insertion acts to prevent coated pit localization and endocytosis. We first identified the region of the FcRII-B2 cytoplasmic domain that is required for rapid internalization. Using a biochemical assay for endocytosis and an immuno-EM assay to determine coated pit localization directly, we found that the distal half of the cytoplasmic domain, particularly a region including residues 18-31, as needed for coated pit-mediated endocytosis. Elimination of the tyrosine residues at position 26 and 43, separately or together, had little effect on coated pit localization and a partial effect on endocytosis of ligand. Since the FcRII-B1 insertion occurs in the membrane-proximal region of the cytoplasmic domain (residue 6) not required for internalization, it is unlikely to act by physically disrupting the coated pit localization determinant. In fact, the insertion was found to prevent endocytosis irrespective of its position in the cytoplasmic tail and appeared to selectively exclude the receptor from coated regions. Moreover, receptors bearing the insertion exhibited a temperature- and ligand-dependent association with a detergent-insoluble fraction and with actin filaments, perhaps in part explaining the inability of FcRII-B1 to enter coated pits. PMID- 1734022 TI - Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity. AB - The development of polarized epithelial cells from unpolarized precursor cells follows induction of cell-cell contacts and requires resorting of proteins into different membrane domains. We show that in MDCK cells the distributions of two membrane proteins, Dg-1 and E-cadherin, become restricted to the basal-lateral membrane domain within 8 h of cell-cell contact. During this time, however, 60 80% of newly synthesized Dg-1 and E-cadherin is delivered directly to the forming apical membrane and then rapidly removed, while the remainder is delivered to the basal-lateral membrane and has a longer residence time. Direct delivery of greater than 95% of these proteins from the Golgi complex to the basal-lateral membrane occurs greater than 48 h later. In contrast, we show that two apical proteins are efficiently delivered and restricted to the apical cell surface within 2 h after cell-cell contact. These results provide insight into mechanisms involved in the development of epithelial cell surface polarity, and the establishment of protein sorting pathways in polarized cells. PMID- 1734024 TI - Direct proof that the primary site of action of cytochalasin on cell motility processes is actin. AB - We have previously described the isolation of a mutant KB cell (Cyt 1 mutant) resistant to the cytotoxic effect of cytochalasin B (CB). The Cyt 1 mutant carries an altered form of beta-actin (beta'-actin) and lacks normal beta-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). Increased resistance of the Cyt 1 mutant to CB in vivo is reflected in altered properties of beta'-actin in vitro (Toyama, S., and S. Toyama. 1988. J. Cell Biol. 107:1499-1504). Here, we show that the mutation in beta-actin is solely responsible for the cytochalasin resistant phenotype of the Cyt mutant. We have isolated a cDNA clone encoding beta'-actin from Cyt 1 cells. Sequence analysis reveals two mutations in the coding region that substitute two amino acid residues (Val139----Met and Ala295-- -Asp). Expression of the beta'-actin cDNA confers cytochalasin resistance upon transformed cytochalasin-sensitive KB cells. Levels of resistance to CB in the transformed cell clones correlate well with amounts of beta'-actin polypeptide. Both of the two mutations in beta'-actin are necessary for the high level expression of cytochalasin resistance. Overall, we conclude that the primary site of action of cytochalasin on cell motility processes in vivo is actin. PMID- 1734023 TI - Perturbations of Drosophila alpha-actinin cause muscle paralysis, weakness, and atrophy but do not confer obvious nonmuscle phenotypes. AB - We have investigated accumulation of alpha-actinin, the principal cross-linker of actin filaments, in four Drosophila fliA mutants. A single gene is variably spliced to generate one nonmuscle and two muscle isoforms whose primary sequence differences are confined to a peptide spanning the actin binding domain and first central repeat. In fliA3 the synthesis of an adult muscle-specific isoform is blocked in flight and leg muscles, while in fliA4 the synthesis of nonmuscle and both muscle-specific isoforms is severely reduced. Affected muscles are weak or paralyzed, and, in the case of fliA3, atrophic. Their myofibrils, while structurally irregular, are remarkably normal considering that they are nearly devoid of a major contractile protein. Also surprising is that no obvious nonmuscle cell abnormalities can be discerned despite the fact that both the fliA1- and fliA4-associated mutations perturb the nonmuscle isoform. Our observations suggest that alpha-actinin stabilizes and anchors thin filament arrays, rather than orchestrating their assembly, and further imply that alpha actinin function is redundant in both muscle and nonmuscle cells. PMID- 1734025 TI - Evidence that the stalk of Drosophila kinesin heavy chain is an alpha-helical coiled coil. AB - Kinesin is a mechanochemical enzyme composed of three distinct domains: a globular head domain, a rodlike stalk domain, and a small globular tail domain. The stalk domain has sequence features characteristic of alpha-helical coiled coils. To gain insight into the structure of the kinesin stalk, we expressed it from a segment of the Drosophila melanogaster kinesin heavy chain gene and purified it from Escherichia coli. When observed by EM, this protein formed a rodlike structure 40-55 nm long that was occasionally bent at a hingelike region near the middle of the molecule. An additional EM study and a chemical cross linking study showed that this protein forms a parallel dimer and that the two chains are in register. Finally, using circular dichroism spectroscopy, we showed that this protein is approximately 55-60% alpha-helical in physiological aqueous solution at 25 degrees C, and approximately 85-90% alpha-helical at 4 degrees C. From these results, we conclude that the stalk of kinesin heavy chain forms an alpha-helical coiled coil structure. The temperature dependence of the circular dichroism signal has two major transitions, at 25-30 degrees C and at 45-50 degrees C, which suggests that a portion of the alpha-helical structure in the stalk is less stable than the rest. By producing the amino-terminal (coil 1) and carboxy-terminal (coil 2) halves of the stalk separately in E. coli, we showed that the region that melts below 30 degrees C lies within coil 1, while the majority of coil 2 melts above 45 degrees C. We suggest that this difference in stability may play a role in the force-generating mechanism or regulation of kinesin. PMID- 1734026 TI - A normally masked nuclear matrix antigen that appears at mitosis on cytoskeleton filaments adjoining chromosomes, centrioles, and midbodies. AB - mAbs were generated against HeLa nuclear matrix proteins and one, HIB2, which selectively stained mitotic cells, was selected for further study. Western blot analysis showed H1B2 antibody detected a protein of 240 kD in the nuclear matrix fractions. The H1B2 antigen was completely masked in immunofluorescently stained interphase cells. However, removing chromatin with DNase I digestion and 0.25 M ammonium sulfate extraction exposed the protein epitope. The resulting fluorescence pattern was bright, highly punctate, and entirely nuclear. Further extraction of the nuclear matrix with 2 M NaCl uncovers an underlying, anastomosing network of 9-13 nm core filaments. Most of the H1B2 antigen was retained in the fibrogranular masses enmeshed in the core filament network and not in the filaments themselves. The H1B2 antigen showed remarkable behavior at mitosis. As cells approached prophase the antigen became unmasked to immunofluorescent staining without the removal of chromatin. First appearing as a bright spot, the antibody staining spread through the nucleus finally concentrating in the region around the condensed chromosomes. The antibody also brightly stained the spindle poles and, more weakly, in a punctate pattern in the cytoskeleton around the spindle. As the chromosomes separated at anaphase, H1B2 remained with the separating daughter sets of chromosomes. The H1B2 antigen returned to the reforming nucleus at telophase, but left a bright staining region in the midbody. Immunoelectron microscopy of resinless sections showed that, in the mitotic cell, the H1B2 antibody did not stain chromosomes and centrioles themselves, but decorated a fibrogranular network surrounding and connected to the chromosomes and a fibrogranular structure surrounding the centriole. PMID- 1734027 TI - Molecular organization of the uvomorulin-catenin complex. AB - The Ca(2+)-dependent cell adhesion molecule uvomorulin is a member of the cadherin gene family. Its cytoplasmic region complexes with structurally defined proteins termed alpha-, beta-, and gamma-catenins. Here we show that A-CAM (N cadherin), another member of this gene family, also associates with catenins suggesting that this complex formation may be a general property of the cadherins. For uvomorulin it has been found that this association with catenins is of crucial importance for the adhesive function, but little is known about the molecular organization of the uvomorulin-catenin complex. Using a combination of biochemical analyses we show that a single complex is composed of one molecule of uvomorulin, one or two molecules of beta-catenin, and one molecule of alpha catenin. Furthermore, beta-catenin seems to interact more directly with uvomorulin. In pulse-chase experiments beta-catenin is already associated with the 135-kD uvomorulin precursor molecule but the assembly of the newly synthesized alpha-catenin into the complex is only detected around the time of endoproteolytic processing. PMID- 1734028 TI - Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases. AB - The site of action of cysteine-proteinases (CPs) and matrix metalloproteinases (MMPs) in the degradation of bone collagen by osteoclasts was investigated by evaluating the effects of the CP-inhibitor trans-epoxy-succinyl-L-leucylamido (4 guanidino)-butane (E-64) and the MMP-inhibitor N-(3-N-benzyloxycarbonyl amino-1-R carboxypropyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide (Cl-1) in an in vitro model system of PTH-stimulated mouse calvaria. In the presence of each of the two inhibitors a large area of collagen free of mineral crystallites was seen adjacent to the ruffled border of the osteoclasts. Following a culture period of 24 h this area proved to be about 10 times larger in inhibitor-treated explants than in controls. Moreover the percentage of osteoclasts in close contact with such demineralized bone areas appeared to be significantly higher in inhibitor treated explants than in control specimens (60% and 5%, respectively). These effects were not apparent when the osteoclastic activity was inhibited with calcitonin. No significant differences were found between the effects of the two inhibitors, E-64 and Cl-1. Our observations indicate that under the influence of inhibitors of MMPs and CPs demineralization of bone by osteoclasts proceeded up to a certain point whereas matrix degradation was strongly inhibited. It is concluded that within the osteoclastic resorption lacuna both CPs and MMPs participate in the degradation of the collagenous bone matrix. PMID- 1734029 TI - Growth and function of primary rabbit kidney proximal tubule cells in glucose free serum-free medium. AB - The properties of primary rabbit kidney proximal tubule cells in glucose-free serum-free medium have been examined. Primary rabbit kidney proximal tubule cells were observed to grow at the same rate, 1.0 doublings/day, both in glucose-free and in glucose-supplemented medium. Growth in glucose-free medium was dependent upon the presence of an additional nutritional supplement, such as glutamine, pyruvate, palmitate, lactate, or beta hydroxybutyrate. Lactate, pyruvate, and glutamate are utilized for renal gluconeogenesis in vivo. The growth of the primary rabbit kidney proximal tubule cells in glucose-free medium was also dependent upon the presence of the three growth supplements insulin, transferrin, and hydrocortisone. Insulin was growth stimulatory to the primary proximal tubule cells in glucose-free medium, although insulin causes a reduction in the phosphoenolpyruvate carboxykinase (PEPCK) activity in these cells. PEPCK is a key regulatory enzyme in the gluconeogenic pathway. In order to evaluate whether or not the primary cells have gluconeogenic capacity, their glucose content was determined. The cells contained 5 pmoles D-glucose/mg protein. However, no significant glucose was detected in the medium. Presumably, the primary cells were either utilizing or storing the glucose made by the gluconeogenic pathway. Consistent with this latter possibility, cellular glycogen levels were observed to increase with time in culture. The effect of glucose on the expression of the alpha I(IV) collagen and laminin B1 chain genes was examined. Northern analysis indicated that the level of alpha I(IV) collagen mRNA was significantly elevated in glucose containing, as compared with glucose deficient, medium. In contrast, laminin B1 chain mRNA levels were not significantly affected by the glucose content of the medium. PMID- 1734030 TI - Entactin promotes adhesion and long-term maintenance of cultured regenerated skeletal myotubes. AB - The basal lamina protein, laminin, has been shown to promote migration and proliferation of cultured skeletal myoblasts, resulting in increased myotube formation. However, skeletal myotubes adhere poorly to a laminin substrate, and long-term cultures of skeletal myotubes on laminin have not been achieved. We have found that cultured satellite cells from bupivacaine-damaged rat skeletal muscle actively proliferate and differentiate on a diluted Matrigel substrate composed of laminin, type IV collagen, heparan sulfate proteoglycan, and entactin. Myotubes cultured on diluted Matrigel are contractile and have never been observed to detach from the culture dish; rather, myotubes generally atrophy after 2-3 weeks in culture. Antibodies directed against the various protein components of Matrigel were used to determine the role of each component in enhancing muscle differentiation. Anti-laminin impaired satellite cell adhesion, whereas antibodies against either type IV collagen or heparan sulfate proteoglycan had no effect. Anti-entactin did not inhibit attachment, proliferation, or fusion of cultured satellite cells; however, myotubes exposed to anti-entactin failed to adhere to the culture dish after spontaneous myotube contractions began. We conclude that entactin is responsible for long-term maintenance and maturation of contractile skeletal myotubes on a diluted Matrigel substrate. This is the first study to assign a biological function for entactin in myogenesis. PMID- 1734031 TI - Urokinase-type plasminogen activator mediates basic fibroblast growth factor induced bovine endothelial cell migration independent of its proteolytic activity. AB - The dependence of urokinase-type plasminogen activator (uPA) induction on endogenous basic fibroblast growth factor (bFGF) activity during endothelial cell migration was investigated utilizing a combination of wounded endothelial cell monolayers and substrate overlay techniques. Purified polyclonal rabbit immunoglobulin G (IgG) against bFGF blocked the appearance of uPA-dependent lytic activity normally observed at the edge of a wounded bovine aortic endothelial (BAE) cell monolayer. Additionally, the migration of cells into the denuded area was inhibited 30-50% by antibodies either to bFGF or to bovine uPA. Incubation of wounded monolayers with either purified bovine uPA or agents able to induce PA activity, such as phorbol myristate acetate (PMA), vanadate, or bFGF, resulted in enhanced migration of cells (28-50%). Anti-bovine uPA IgG blocked a significant fraction (25%) of BAE cell migration induced by exposure to exogenous bFGF. The role of uPA in migration of wounded BAE cells was not dependent on plasmin generation. Furthermore, the amino terminal fragment (ATF) of human recombinant (hr) uPA, which is enzymatically inactive, stimulated endothelial cell movement in the presence of anti-bFGF IgG. These results suggest that BAE cell migration from the edge of a wounded monolayer is dependent upon local increases of uPA mediated by endogenous bFGF. Moreover, the data support the conclusion that migration is stimulated via a signalling mechanism dependent upon occupancy of the uPA receptor but independent of uPA-mediated proteolysis. PMID- 1734032 TI - Modulation of nuclear statin expression in rat thyroid follicle cell following administration of thyroid stimulating hormone. AB - This study was designed to examine the state of proliferation in the rat thyrocyte following the administration of thyroid stimulating hormone (TSH). An immunohistochemical technique involving the use of a monoclonal antibody to statin, a nonproliferation-specific nuclear antigen, was developed to measure the subpopulation of cells that have ceased to divide. Following the random assignment of young male Sprague-Dawley rats into various groups, the rats in the control group received a single intraperitoneal (i-p) injection of normal saline, whereas the experimental groups received single i-p injections of TSH at doses of 0.25, 0.50, and 1.0 IU, respectively. All rats were subsequently sacrificed in groups of three at 1, 2, 4, and 24 hours. The statin antibody label was readily identified within the follicle cell nucleus. Results revealed a statistically significant transient decrease in the mean percent statin-positive nuclei in the TSH-treated groups. The time- and dose-dependent effect of TSH was maximal at 2 hours and no longer discernible at 24 hours. A second experiment involving the chronic administration of TSH (i-p 0.25 IU twice daily) resulted in a cumulative response with a statistically significant progressive decrease in the mean percent of statin-positive nuclei at 5 and 10 days, returning to near normal values 5 days following the cessation of treatment. Determination of the nuclear optical density of the statin reaction product by image analysis techniques revealed that a single injection of TSH resulted in a rapid disappearance of the statin nuclear protein. This result suggests that the disappearance of statin in the nucleus appears to reflect the event of cells leaving the nondividing quiescent state to resume the cell cycle traverse following the administration of TSH. The disappearance of statin appears as an early nuclear event that parallels the earliest known cytoplasmic pinocytotic response to TSH in the rat thyroid follicle cell. PMID- 1734033 TI - Polarity in the transcytotic processing of apical and basal membrane-bound peroxidase-polylysine conjugates in MDCK cells. AB - A conjugate of horseradish peroxidase (HRP) to poly(L-lysine) (PLL) was used to characterize a non-lysosomal proteolytic compartment in the MDCK Strain I epithelial cell line. This compartment is expressed in a polar fashion, and is capable of degradation of the PLL moiety in the conjugate followed by release of HRP via a basal-to-apical, but not apical-to-basal, transcytotic pathway. This uptake, cleavage, and transport process appears to require approximately 2 hr, as there is a 2 hr lag-time between conjugate administration to the basal surface and HRP release to the apical medium. Monensin (10 microM) failed to inhibit this process, indicating that participation of the trans-Golgi network (TGN) in the trafficking of internalized conjugate is not the rate-determining step. Inhibition of HRP transport was found to be elicited by 50 micrograms/ml leupeptin, but only when applied to the basal surface. Brief trypsinization of either the basal or apical surfaces of cells preloaded with HRP conjugate showed no appreciable inhibitory effect on the apical release of HRP, indicating that an intracellular compartment rather than surface-bound enzymes is responsible for the degradation of the PLL moiety in the conjugate. Our results demonstrate the presence of an intracellular proteolytic compartment which is accessible in the basal-to-apical, but not apical-to-basal, transport pathway; and this compartment can be exploited for the transcytosis of membrane-bound molecules. PMID- 1734034 TI - Parathyroid hormone-related protein production by primary cultures of mammary epithelial cells. AB - Parathyroid hormone-related protein (PTHrP) plays a major role in the pathogenesis of malignant hypercalcemia, but has also been found in fetal and adult non-neoplastic tissues. Among them, lactating mammary gland was shown to produce PTHrP, and high levels of PTHrP were measured in milk. However, the regulation of PTHrP production by breast cells is still unknown. Primary cultures of mammary cells isolated from rat lactating glands were grown on collagen gels in an insulin/epidermal growth factor (EGF)-supplemented medium. Under these conditions, mammary cells displayed an epithelial phenotype and their number increased more than twofold after 1 week in culture. At that time, the cells were capable of producing immunoreactive PTHrP (range: 25 to 150 pg/10(5) cells x 24 h) and PTH-like bioactivity, as indicated by a 60% increase in cyclic adenosine monophosphate (cAMP) production induced by mammary epithelial cell conditioned medium in the PTH-responsive osteoblast-like UMR-106 cell line. When cell proliferation was hindered by lowering plating density, by removing medium supplements, or by adding transforming growth factor (TGF)-beta, a well-known autocrine inhibitor of mammary epithelial cell growth. PTHrP production was increased. In contrast, the omission of EGF or addition of specified anti-EGF antibodies decreased PTHrP production. In conclusion, primary cultures of mammary epithelial cells isolated from lactating rat were shown for the first time to produce PTHrP in vitro. This production was higher in the presence of EGF and could be modulated by cell growth rate. PMID- 1734035 TI - Enhanced wound healing in animal models by interferon and an interferon inducer. AB - Healing of wounds is a significant biological process that involves the interactions of different cell types, growth factors, cytokines, and extracellular matrix molecules. Mice and rats were treated in vivo with interferon (IFN) alpha/beta or polyinosinic-polycytidylic acid (Poly I:C), a ds RNA, a potent inducer of IFN. We observed faster and enhanced closure of wounds as compared to untreated controls on day 7 (wound area measured on Macintosh II CX using NIH image 1.30u program), increased migration of dermal fibroblasts in the wound bed, complete re-epithelialization evidenced by routine histology and scanning electron microscopic procedures, and increased collagen synthesis, which correlates to greater tensile strength. In addition, classical immunofluorescence procedures using frozen sections showed that dermal fibroblasts synthesized much more laminin following Poly I:C treatment, whereas no effect was observed on fibronectin synthesis. These results suggest that Poly I:C and IFN treatment result in a faster restoration of tissue integrity in both full skin punch biopsy and skin incision models. PMID- 1734036 TI - Inhibition of heme synthesis decreases transferrin receptor expression in mouse erythroleukemia cells. AB - The coordination of transferrin receptor (TfR) expression and heme synthesis was investigated in mouse erythroleukemia (MEL) cells of line 707 treated with heme synthesis inhibitors or in a variant line Fw genetically deficient in heme synthesis. Cells of line 707 were induced for differentiation by 5 mM hexamethylene bisacetamide (HMBA). TfR expression increased in the course of induction, as judged by increased TfR mRNA synthesis, increased cytoplasmic TfR mRNA level, and by the increased number of cellular 125I-Tf binding sites. Addition of 0.1 mM succinylacetone (SA) decreased cellular TfR to the level comparable with the uninduced cells. The decrease was reverted by the iron chelator desferrioxamine (DFO) but not by exogenous hemin. In short-term (1-2 hours) incubation, SA inhibited 59Fe incorporation from transferrin into heme, whereas total cellular 59Fe uptake was increased. A decrease in TfR mRNA synthesis was apparent after 2 hours of SA treatment. Conversely, glutathione peroxidase mRNA synthesis, previously shown to be inducible by iron, was increased by SA treatment. Cells of heme deficient line Fw did not increase the number of Tf binding sites after the induction of differentiation by 5 mM sodium butyrate. SA had no effect on TfR expression in Fw cells. The results suggest that the depletion of cellular non-heme iron due to the increase in heme synthesis maintains a high level of transferrin receptor expression in differentiating erythroid cells even after the cessation of cell division. PMID- 1734037 TI - Expression of exogenous c-myc oncogene does not initiate DNA synthesis in primary rat hepatocyte cultures. AB - Cultured hepatocytes from adult rats stimulated with combinations of growth factors enter into S phase but do not undergo multiple rounds of DNA synthesis nor mitosis. We have examined the potential of an introduced oncogene to induce alterations in the DNA synthetic activity of the cultured hepatocytes in response to epidermal growth factor (EGF). Overexpression of c-myc did not initiate significant DNA synthesis in rat hepatocyte cultures alone, although it cooperated with added EGF to super-induce thymidine incorporation into DNA. From our results, it is suggested that EGF is also necessary to initiate hepatocyte DNA synthesis probably by inducing a battery of cell cycle-related genes if incubated with c-myc transfected cultures for only 5 hours. Hepatocyte polypeptides reacting with anti-MYC antisera were found to migrate between 55-67 KDa in SDS-PAGE; only the 64-67 KDa species were found to be phosphorylated, and the observed size heterogeneity may be due to proteolytic degradation or may reflect presently unknown posttranslational modifications. PMID- 1734038 TI - Abnormal extracellular matrix and excessive growth of human adult polycystic kidney disease epithelia. AB - Human autosomal dominant polycystic kidney disease (ADPKD) epithelia were grown in primary monolayer cultures and their properties compared with intact kidney epithelial cultures derived from individually microdissected normal human kidney proximal convoluted tubules (PCT), proximal straight tubules (PST), and cortical collecting tubules (CCT). In vivo, ADPKD cyst epithelia exhibited a thickened basement membrane, and immunofluorescence demonstrated the presence of laminin, fibronectin, type IV collagen, and heparan sulfate proteoglycan in basement membranes and type I collagen in the interstitium. ADPKD epithelia grown in culture synthesized and secreted basally a unique, extracellular matrix that took the form of proteinaceous spheroids when the cells were grown on dried, type I collagen. Incorporation of H2[S35O4] into basement membrane extracts was increased more than ten-fold in ADPKD epithelia by comparison to normal PST and CCT. In addition to incorporation into the normal tubular basement membrane 220 kD band, radioactivity was also seen at 175 kD and 150 kD in ADPKD extracts. Growth in culture of cyst-lining ADPKD epithelia was more rapid than normal tubules, and was abnormal since there was no absolute requirement for added extracellular matrix. However, when ADPKD epithelia were grown on different, exogenous matrix protein components, a profound influence on both structure and epithelial cell proliferation was seen. Growth on a complete basement membrane three-dimensional gel derived from the Engelbreth-Holm-Swarm (EHS) sarcoma led to a reduction in the numbers of spheroids and increase in amorphous filaments. Incorporation of [3H]-thymidine into ADPKD epithelia was greater than into normal PCT, PST, and CCT and was also greatly modified by the type of extracellular matrix components provided. In studies using single matrix components, the strongest proliferative response was seen when ADPKD epithelia were plated on type I collagen greater than type IV collagen greater than fibronectin greater than laminin. These findings suggest that the excessive growth of cyst-lining epithelia may be, at least in part, a result of abnormal basement membrane and extracellular matrix production by ADPKD cells. PMID- 1734039 TI - Differential regulation of the expression of transforming growth factor-beta mRNAs by growth factors and retinoic acid in chicken embryo chondrocytes, myocytes, and fibroblasts. AB - Transforming growth factor-beta (TGF-beta) autoregulates its expression in several mammalian cell types. We now report that addition of TGF-beta s 1, 2, and 3 to primary chicken embryo cells differentially affects expression of the messenger RNAs for the different TGF-beta isoforms depending on the cell type. In cultured sternal chondrocytes, addition of TGF-beta s 1, 2, or 3 results in an increase in the steady-state levels of the messenger RNAs for TGF-beta s 2 and 3, but does not change expression of TGF-beta 4 mRNA. In contrast, in cultured cardiac myocytes, addition of TGF-beta s 1, 2, or 3 results in an increase in expression of TGF-beta s 3 and 4 mRNAs, but does not change expression of TGF beta 2 mRNA. Moreover, expression of TGF-beta s 2, 3, and 4 mRNAs is not affected by addition of any of the TGF-beta s to fibroblasts. Addition of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or interleukin-1 (IL-1) to these chicken cells also has differential effects on expression of the different TGF-beta mRNAs depending on the cell type. Retinoic acid also has contrasting effects on chondrocytes and myocytes either increasing or decreasing, respectively, expression of TGF-beta s 2 and 3 mRNAs and TGF-beta 2 protein. Our results indicate a complex pattern of regulation of the different TGF-beta genes by themselves as well as by PDGF, EGF, IL-1, dexamethasone, TPA, and retinoic acid in chicken embryo cells. PMID- 1734040 TI - Increased peptidylarginine deiminase expression during induction of prolactin biosynthesis in a growth-hormone-producing rat pituitary cell line, MtT/S. AB - Insulin and type I insulin-like growth factor (IGF-I) suppressed growth hormone (GH) expression followed by the induction of prolactin (PRL) biosynthesis in MtT/S cells cultured with normal sera. Insulin also increased the peptidylarginine deiminase activity in a dose-dependent manner. The increase was detectable at 1 ng/ml and reached a maximum (about 16-fold higher than the control) at 1 micrograms/ml. IGF-I showed similar but less prominent effects. The enzyme activity started to increase by 15 hr after the addition of insulin (500 ng/ml), and reached a plateau level at 48 hr. There were concurrent increases in the enzyme mRNA level, enzyme biosynthesis, and enzyme protein contents detected by Northern blot hybridization, [35S]-amino-acid incorporation, and Western immunoblot analysis, respectively. Two-color immunofluorescence staining at 1 day after the insulin addition detected a small number of peptidylarginine-deiminase positive cells (about 1% of the total cells) which were also GH-positive. The enzyme-positive cells increased to 12% on day 2 and to 24-26% on days 4-6. PRL positive cells first appeared in the enzyme-positive cell population on day 2, and PRL-positive, enzyme-negative cells appeared later. These results suggest that peptidylarginine deiminase expression increases in association with the hormone switching in MtT/S cells. When the cells were cultured in a steroid depleted medium, insulin failed to increase the enzyme activity. The insulin action could be specifically restored by estrogen, indicating estrogen-insulin synergism in regulation of the enzyme expression. PMID- 1734041 TI - Rapid and biologically safe diagnosis of African swine fever virus infection by using polymerase chain reaction. AB - In order to circumvent the need for infectious virus for the diagnosis of African swine fever (ASF), we established the polymerase chain reaction (PCR) technique for the detection of ASF virus (ASFV) DNA. A 740-bp fragment that originated from the conserved region of the viral genome was partially sequenced. From this sequence, four PCR primers and one oligonucleotide probe were designed and synthesized. A specific 640-bp PCR product was amplified by using oligonucleotides 1 and 5 as primers and extracts of the following samples as templates: organs and plasma obtained from ASFV-infected pigs, ASFV-infected cell cultures, and cloned DNA fragments containing the same conserved genomic region as that in the original 740-bp clone. No specific reaction products were observed in the corresponding controls. The identities of the PCR products were confirmed either by a second amplification with nested primers or by hybridization with a specific, biotinylated oligonucleotide probe. PCR proved to be a quicker and more sensitive method than virus isolation followed by the hemadsorption test when spleen and plasma samples from experimentally ASFV-infected pigs were tested. Furthermore, cloned virus DNA could be used as a positive control in the place of a live virus control. This is advantageous whenever the use of live virus is undesirable. PMID- 1734042 TI - Evaluation of a Treponema pallidum western immunoblot assay as a confirmatory test for syphilis. AB - Tests for the detection of antibodies to Treponema pallidum are recommended for the confirmation of reactive nontreponemal test results and the accurate diagnosis of syphilis. The present-day use of Western blot (immunoblot) technology for the diagnosis of retroviruses prompted the development and evaluation of a Western blot assay with whole-cell T. pallidum as the antigen. The assay detected antibodies in syphilitic serum or plasma from dilutions of specimens incubated overnight with test strips. A test was considered positive when at least three of four major antigens having molecular masses of 15.5, 17, 44.5, and 47 kDa were detected. The Western blot assay had 93.8% sensitivity and 100% specificity for clinically defined samples. The Western blot assay was compared with double-staining fluorescent treponemal antibody absorption [FTA-ABS (DS)], which had a sensitivity and a specificity of 91.7 and 92.0%, respectively. Dilution series studies of syphilis-positive specimens indicated that the Western blot assay has an endpoint of reactivity at least 3 to 4 serial dilutions greater than that for FTA-ABS (DS). Overall, the greater than 95% agreement between the Western blot assay and FTA-ABS (DS) for clinically defined specimens indicates that the sensitivity of the Western blot assay is equal to or greater than that of FTA-ABS (DS). The Western blot assay demonstrated no false-positive or equivocal reactivities for nonsyphilitic specimens, including normal specimens (both plasma and serum), biological false-positives, and specimens with elevated gamma globulin or antinuclear antibody. We conclude that the high sensitivity and specificity of the T. pallidum Western blot assay, together with its simplicity and objectivity, make it a good confirmatory test for syphilis. PMID- 1734043 TI - Reevaluation of the API 20E identification system versus conventional biochemicals for identification of members of the family Enterobacteriaceae: a new look at an old product. AB - The API 20E bacterial identification system has been used for 19 years, often as the standard with which other identification systems are compared. Because the accuracy of this system compared with conventional biochemical tests has not been determined in many years, we evaluated the API 20E linear strip by using 291 typical and atypical strains of the family Enterobacteriaceae taken from a culture collection. At 24 h, the API 20E correctly identified by genus and species 229 of 291 (78.7%) of the strains, using Salmonella and Shigella serotyping where indicated. At 48 h, 95.2% were correctly identified by using additional biochemical tests as recommended by the manufacturer. The API 20E misidentified eight (2.7%) strains; these strains were not limited to any particular genus. When 81 of these Enterobacteriaceae strains were arranged into a weighted assortment correlating to the frequency with which they might be found in a clinical laboratory, the API 20E correctly identified 71 (87.7%) at 24 h and 78 (96.3%) at 48 h. This evaluation concluded that the accuracy of the identification of Enterobacteriaceae strains at 24 h (78.7%) may be significantly lower than that of earlier evaluations. However, there is no significant difference in the ability of the API 20E to correctly identify "challenge" type organisms (229 of 291) versus routine hospital isolates (71 of 81) (P greater than 0.05), but the system is not as accurate as the conventional biochemical method of identification. PMID- 1734044 TI - Characterization of Neisseria meningitidis serogroup C by multilocus enzyme electrophoresis and ribosomal DNA restriction profiles (ribotyping). AB - We compared multilocus enzyme electrophoresis (MEE) and ribosomal DNA fingerprinting (ribotyping) for subtyping 44 strains of Neisseria meningitidis serogroup C that were isolated in Los Angeles County, California, between December 1985 and July 1986. The isolates were divided into six enzyme types (ETs) by MEE, but 36 of the isolates were clustered in one ET, 3. The same isolates were divided into 17 ribotypes by use of restriction endonucleases ClaI, EcoRI, and XhoI. Twenty of the 36 ET 3 isolates were divided into 17 ribotypes by use of restriction endonucleases ClaI, EcoRI, and XhoI. Twenty of the 36 ET 3 isolates were grouped in a single ribotype, J. The rate of infection with ribotype J strains was higher in the southern part of the study area than in the northern part. Isolates from each of eight pairs (each isolate pair was cultured from the same patient from the same or different sites) were found identical by MEE, but ribotyping revealed a difference in one pair. In this study, ribotyping showed a greater discriminating capacity than MEE for subtyping N. meningitidis serogroup C, but the epidemiologic relevance of this increased sensitivity needs further assessment. PMID- 1734045 TI - Rapid detection of group A streptococci: comparative performance by nurses and laboratory technologists in pediatric satellite laboratories using three test kits. AB - Rapid tests for detecting group A streptococci in throat swabs are often performed outside hospitals or commercial laboratories by individuals with little or no technical training. We compared the abilities of nurses and technologists to perform and interpret three commercial kits (Directigen 1-2-3, ICON Strep A, and Culturette Brand 10-Minute Strep A ID) in three hospital satellite locations (the emergency department, a walk-in emergency clinic, and a general pediatric clinic). When the three tests were compared with culture, the sensitivities of the tests as performed by nurses and technologists, respectively, were 39 versus 44% for Directigen, 55 versus 51% for Culturette, and 72 versus 39% for ICON. A significant difference in sensitivity was found only with ICON tests. This result was largely explained by the tendency of technologists to test moist swabs, while nurses generally processed dry swabs; ICON test sensitivity was significantly greater with dry swabs. The specificities of Directigen and ICON tests performed by nurses and technologists were high (97 to 100%). The difference in the specificities of the Culturette test as determined from results obtained by nurses and technologists (80 versus 98%) was due to the tendency of one nurse to overinterpret the latex agglutination reaction. Analysis of the accuracies of the tests during practice periods compared with the accuracies of the tests during the study periods revealed statistically significant improvement in test performance. We conclude that these tests are specific but not sensitive when performed by nurses and technologists in satellite laboratories. With one exception, nurses and technologists performed the tests with comparable accuracy after brief training periods. PMID- 1734046 TI - Analyses of Ehrlichia canis and a canine granulocytic Ehrlichia infection. AB - Ehrlichia canis and canine granulocytic Ehrlichia sp. (CGE) infect canine monocytes and granulocytes, respectively. E. canis has been cultured in vitro and used to develop an immunofluorescence assay. CGE has not been cultured, and a serologic assay is not available. The sera of dogs infected with CGE were reported to react with E. canis by immunofluorescence. In this study, the temporal response of immunoglobulin G (IgG) was determined by an enzyme-linked immunosorbent assay (ELISA) with purified E. canis antigen in four dogs experimentally infected with E. canis, in two dogs experimentally infected with CGE, and in one dog infected with E. canis and subsequently infected with CGE. E. canis-infected dogs developed an IgG ELISA result of 1.5 or greater for the optical density signal/noise ratio by 2 months postinfection. CGE challenge of a dog with a previous E. canis infection induced an anamnestic increase in the IgG ELISA result; however, CGE infection alone did not induce a significant IgG ELISA response. Western immunoblot analysis showed that dogs infected with E. canis developed antibodies initially that reacted with low-molecular-mass proteins (30, 24, and 21 kDa) and subsequently with higher-molecular-mass proteins (160, 100, 78, 64, 47, and 40 kDa). In contrast, CGE-infected dogs showed reactions with the same higher-molecular-mass proteins of E. canis but, unlike E. canis-infected dogs, not with the low-molecular-mass proteins of E. canis. Of 10 serum samples collected in the field of Indonesia from dogs with tropical canine pancytopenia, all had an optical density signal minus noise value of 2.54 or greater in the IgG ELISA and reacted with E. canis antigen in a pattern similar to that of serum samples from dogs experimentally infected with E. canis in Western immunoblotting. This study suggests that the IgG ELISA and Western immunoblotting with purified E. canis as the antigen are useful in distinguishing between E. canis and CGE infections in dogs. PMID- 1734047 TI - Serotype prevalence of Candida albicans from blood culture isolates. AB - Blood culture isolates of Candida albicans were collected from 102 patients in Seattle, Wash., hospitals (n = 77) and Hong Kong (n = 25). The patients were classified by immune status into two groups. Group I patients were severely immunosppression, and group II patients had underlying risk factors for candidemia but no underlying immunosuppression. Serotyping by Hasenclever tube agglutination was done. In the Seattle area, the odds of fungemia with type B C. albicans were 3.62 times greater than the odds of type B fungemia in group II patients. Although the odds ratio could not be computed for Hong Kong patients, the direction of the relationship in this population was consistent with the data on Seattle patients. Despite the magnitude of the odds ratios, the relative prevalence of type B over type A in group I compared with group II was not significant when analyzed separately by region, probably because of relatively low numbers of isolates in group II. Accepting that the effect of immune status on serotype is equivalent across regions but presupposing that a regional effect on type B prevalence exists, the pooled odds for fungemia with serotype B in group I patients are increased 5.4-fold over those of group II patients. Logistic regression analysis controlling for region gave similar results. PMID- 1734049 TI - Mycobacterium paratuberculosis cultured from milk and supramammary lymph nodes of infected asymptomatic cows. AB - Milk and supramammary lymph node samples were obtained from asymptomatic cows infected with Mycobacterium paratuberculosis at the time of slaughter. Of 81 supramammary lymph node samples, 22 (27%) were culture positive for M. paratuberculosis. Of 77 milk samples, 9 (11.6%) were culture positive. The prevalence of supramammary lymph node or milk infection was highest with heavy fecal shedding of M. paratuberculosis and lowest with light shedding. The serologic status of the cow was not useful for predicting the risk of supramammary lymph node or milk infection. Shedding of M. paratuberculosis occurs in the milk of asymptomatic infected cows but, apparently, less frequently than previously reported for symptomatic cows. PMID- 1734048 TI - Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay. AB - There is no standard immunoassay for evaluating immune responses to meningococcal vaccines. We developed an enzyme-linked immunosorbent assay to measure total levels of antibody to Neisseria meningitidis group A capsular polysaccharide. Five laboratories measured the antibody levels in six paired pre- and postvaccination serum samples by using the enzyme-linked immunosorbent assay. Methylated human serum albumin was used to bind native group A polysaccharide to microtiter plate surfaces. The between-laboratory coefficients of variation for pre- and postvaccination sera had ranges of 31 to 91 and 17 to 31, respectively. The mean laboratory coefficients of variation for pre- and postvaccination sera, respectively, were 17 and 11 (Molecular Biology Laboratory, Centers for Disease Control), 12 and 15 (Immunodiagnostic Methods Laboratory, Centers for Disease Control), 22 and 19 (Dana-Farber Cancer Institute), 38 and 38 (Bacterial Polysaccharide Laboratory, U.S. Food and Drug Administration), and 11 and 10 (Praxis Biologics, Inc.). Standardization of this enzyme-linked immunosorbent assay should allow interlaboratory comparison of meningococcal vaccine immunogenicity, thus providing a laboratory-based assessment tool for evaluating meningococcal vaccines. PMID- 1734050 TI - Evaluation of a commercially available second-generation immunoglobulin G enzyme immunoassay for detection of Helicobacter pylori infection. AB - We evaluated a commercially available second-generation anti-H. pylori immunoglobulin G enzyme immunoassay (EIA) (Cobas Core Anti-Helicobacter pylori EIA; Roche S. A., Basel, Switzerland) for serodiagnosis of H. pylori infection. The results of the assay were assessed in relation to the results of bacterial culture, urease testing, and histological Giemsa stain of gastric biopsy specimens from 1,134 patients with a variety of symptoms relating to the upper gastrointestinal tract. H. pylori was detected in biopsy specimens from 660 (58.2%) patients: 6 had a normal mucosa, 123 had chronic gastritis only, and 531 were found to have chronic active gastritis by histology; endoscopy showed duodenal and gastric ulcers in 137 and 64 patients of the last two groups, respectively. The test was evaluated with different age and ethnic groups. The prevalence, sensitivity, specificity, and positive and negative predictive values were, respectively, (i) for Belgian patients between 18 and 40 years old, 34, 93, 95, 91, and 96%; (ii) for Belgian patients more than 40 years old, 53, 96, 91, 93, and 95%; and (iii) the Mediterranean patients more than 17 years old, 87, 94, 70, 95, and 64%. All sera showing discordant immunoassay results compared with the results of histology and culture of biopsy specimens, as well as those with borderline immunoassay results, were tested further by immunoblotting. Among the EIA results considered false negative, we demonstrated an absence of seroconversion in 14 of 19 patients tested by immunoblotting. Among the EIA results considered false positive, immunoblotting showed the presence of specific antibodies in 28 of 37 patients tested. Among the borderline results obtained in the first assay with 22 patients' sera, a second assay showed positive results in 10 patients (8 were positive by immunoblotting) and negative reactions in 10 patients (9 were negative by immunoblotting), whereas 2 remained borderline. These data indicate that sera showing borderline immunoassay results must be tested again. In conclusion, this commercially available second-generation EIA, which is easy and quick to perform, was found highly reliable for the serodiagnosis of H. pylori infection. PMID- 1734051 TI - 15NH4+ excretion test: a new method for detection of Helicobacter pylori infection. AB - A noninvasive test for the detection of Helicobacter pylori infection that uses [15N]urea as a tracer has been established. The principle the test is based on is the strong urease activity of H. pylori. After oral ingestion, [15N]urea is broken down into ammonia and carbon dioxide by H. pylori urease in the stomach. The ammonia is absorbed into the blood and excreted in the urine. The amount of [15N]urea, reflecting the magnitude of H. pylori infection, is evaluated by measuring the abundance and excretion rate of 15N in ammonia in the urine. Thirty six patients were examined in our study. The 15N excretion rates in urine ammonia of patients who were H. pylori positive were significantly higher than those of H. pylori-negative patients (P less than 0.05). Twenty-three patients were H. pylori positive by Gram stain and culture. The sensitivity of the 15NH4 excretion test compared with these techniques was 96%, and no false positives were obtained. The 15NH4+ excretion rates of 13 H. pylori-negative subjects were all in the normal range (less than 0.3%). This method is a simple, precise, highly sensitive, noninvasive, nonradioactive test. It could be used for diagnosis as well as for the followup of patients receiving H. pylori eradication therapy, especially children and pregnant women. It could also be used in epidemiological investigation of H. pylori infection in a general population. PMID- 1734052 TI - Sensitive detection of Helicobacter pylori by using polymerase chain reaction. AB - A polymerase chain reaction (PCR) for the specific detection of Helicobacter pylori was developed with a single primer pair derived from the nucleotide sequence of the urease A gene of H. pylori. We achieved specific amplification of a 411-bp DNA fragment in H. pylori. After 35 cycles of amplification, the product could be detected by agarose gel electrophoresis and contained conserved single HinfI and AluI restriction sites. This fragment was amplified in all 50 strains of H. pylori tested, but it was not detected in other bacterial species, showing the PCR assay to be 100% specific. PCR DNA amplification was able to detect as few as 10 H. pylori cells. PCR detected H. pylori in 15 of 23 clinical human gastric biopsy samples, whereas culturing and microscopy detected H. pylori in only 7 of the samples found to be positive by PCR. Additional primer pairs based on the urease genes enabled the detection of H. pylori in paraffin-embedded human gastric biopsy samples. The detection of H. pylori by PCR will enable both retrospective and prospective analyses of clinical samples, elucidating the role of this organism in gastroduodenal disease. PMID- 1734053 TI - Capnocytophaga canimorsus septicemia caused by a dog bite in a hairy cell leukemia patient. AB - Fatal septicemia developed in a splenectomized patient with hairy cell leukemia following a dog bite. Capnocytophaga canimorsus, a slowly growing gram-negative bacillus, was isolated from the patient's blood. Although a rare complication of dog bites in the normal population, this bacterium should be suspected and promptly treated in immunologically compromised dog bite victims. Furthermore, immunocompromised patients should be made aware of the dangers of dog ownership. PMID- 1734054 TI - Comparison of the E test and microdilution for detection of beta-lactam-resistant mutants that are stably derepressed for type I beta-lactamase. AB - The activities of cefotaxime, ceftazidime, piperacillin, and aztreonam were compared in the E test and broth microdilution test against 30 gram-negative bacterial mutants derepressed for type I beta-lactamases. The results demonstrated complete agreement between 24-h MICs of 80 to 83% and essential agreement between 24-h MICs of 90 to 97%. When sufficient growth was present for the E test to be read at 6 h, the essential agreement between 6- and 24-h E-test MICs was 100% for ceftazidime, piperacillin, and aztreonam and 85% for cefotaxime. PMID- 1734055 TI - Detection of human immunodeficiency virus type 1 antibody by using commercially available whole-cell viral lysate, synthetic peptide, and recombinant protein enzyme immunoassay systems. AB - A total of 575 serum specimens received for human immunodeficiency virus type 1 (HIV-1) antibody determination were tested prospectively by enzyme immunoassay with a whole-cell viral lysate (VL) (Genetic Systems Corp.), a synthetic peptide (SP) (United Biomedical, Inc.), and a recombinant protein (RCP) (Syva Co.). Concordance of all three antigens was noted for 559 of 575 (97.2%) specimens tested. Of the specimens tested, 90 (15.7%) were positive and 469 (84.3%) were negative. Retrospective testing by SP and RCP of 86 specimens indeterminate for HIV-1 antibody by VL, Western blot (immunoblot), and immunofluorescence was also performed. The results of both phases of this study indicate that the specificity of the three antigens is RCP greater than SP greater than VL. As noted from the prospective phase, the sensitivities of the antigens appear to be equivalent, indicating that the RCP and SP systems could be used in place of, or to confirm, a VL enzyme immunoassay screening test. PMID- 1734057 TI - Rapid diagnosis of Brucella melitensis in blood: some operational characteristics of the BACT/ALERT. AB - A clinical isolate of Brucella melitensis was detected in a blood culture with the BACT/ALERT after an incubation period of 2.8 days. Dilution studies revealed an inverse linear relationship between the log of the initial concentration of the organism and the time to detection of a positive result. Reproducibility studies demonstrated a mean detection time of 48 +/- 1 h in 8 of 10 replicates seeded with a stock containing 10(2) CFU/ml. PMID- 1734056 TI - Occurrence of resistance to vibriostatic compound 0/129 in Vibrio cholerae 01 isolated from clinical and environmental samples in Bangladesh. AB - Fifty-one Vibrio cholerae 01 strains isolated from 734 natural water and plankton samples and 31 rectal swabs were examined. Of these strains, 32 (62.7%) were found to be resistant to vibriostatic compound 0/129. When antibiograms using the antibiotics ampicillin, tetracycline, chloramphenicol, trimethoprim sulfamethoxazole, furoxan, and gentamicin were done, it was observed that there was a correlation of sensitivity to 0/129 with selected antibiotics. Only the Ogawa E1 Tor (72% of strains resistant) and Inaba classical (28% of strains resistant) biotypes of V. cholerae 01 showed resistance to 0/129. On the other hand, all Inaba E1 Tor and Ogawa classical strains were susceptible to 0/129. The 32 0/129-resistant and 19 0/129-sensitive isolates of V. cholerae 01 were tested for the presence of plasmid DNA. Only two strains isolated from the environment were found to carry a plasmid, and they were also found to be resistant to 0/129 and gentamicin. Thus, 0/129 resistance, although more common than previously suspected, is concluded not to be plasmid mediated in the strains tested in this study. PMID- 1734058 TI - Clinical demonstration of isolation of Nocardia asteroides on buffered charcoal yeast extract media. AB - Nocardia asteroides was isolated only from sputum samples, obtained from three patients with pulmonary nocardiosis, that had been cultured onto buffered charcoal-yeast extract (BCYE) and selective BCYE media as part of laboratory workups for Legionella species. A decontamination procedure with low-pH pretreatment (KCl-HCl solution) had been performed on the sputa prior to culture onto the BCYE media because direct cultures on the media were overgrown with commensal microflora. Chalky white colonies, 0.5 to 1.0 mm in diameter, that were subsequently identified as N. asteroides grew well on the BCYE media. Thus, the techniques and the selective media used for Legionella species were useful for isolating Nocardia species from sputum. PMID- 1734059 TI - Ovalbumin blocking improves sensitivity and specificity of immunoglobulin M immunoblotting for serodiagnosis of patients with erythema migrans. AB - To improve the serodiagnosis of erythema migrans, we evaluated how sensitivity and specificity of immunoblotting are influenced by antigen concentration and blocking conditions. We found that an antigen concentration of 0.5 micrograms per lane in concert with ovalbumin blocking of the nitrocellulose provided the best results. In this case, 81% of the erythema migrans had positive immunoglobulin M tests, whereas only 33% were positive in a flagellum enzyme-linked immunosorbent assay (ELISA) and 28% were positive in a sonicate ELISA. PMID- 1734060 TI - Recovery of Histoplasma capsulatum from blood in a commercial radiometric Mycobacterium medium. AB - We report the recovery of Histoplasma capsulatum from blood specimens cultured for Mycobacterium sp. in BACTEC 13A radiometric medium. H. capsulatum was recovered from six of eight blood specimens submitted for mycobacterial cultures from five human immunodeficiency virus-positive individuals. Initial positive metabolic signals occurred at a mean of 11 days, but no organisms were detected with acid-fast stains. The bottles remained positive, and after an additional incubation (mean, 8 days), yeast cells morphologically compatible with H. capsulatum were detected when aliquots were stained with acridine orange. Therefore, when radiometric mycobacterial blood cultures with persistent positive metabolic signals and negative acid-fast stains are encountered, acridine orange staining and subculturing for a variety of microorganisms, including fungi, e.g., H. capsulatum, should be considered. PMID- 1734061 TI - Isolation of Yersinia enterocolitica serovar O8 from free-living small rodents in Japan. AB - Yersinia species were isolated from 65 of 223 free-living small mammals trapped in 10 regions on Honshu Island in Japan. Of the 65 strains isolated, 1 was Yersinia enterocolitica serovar O3, 8 were Y. enterocolitica O5, 6 were Y. enterocolitica O8, 3 were Y. enterocolitica O9, and 1 was Yersinia pseudotuberculosis 4b. Of the six Y. enterocolitica O8 strains, five were positive for autoagglutination, Ca2+ dependence, and the 45-MDa virulence plasmid and showed high pathogenicity for mice. PMID- 1734062 TI - Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus (the Streptococcus milleri group): association with different body sites and clinical infections. AB - The associations of Streptococcus intermedius, S. constellatus, and S. anginosus (the three species of the S. milleri group) with clinical infections and sites of isolation were investigated by using a simple biochemical scheme to identify a collection of 153 clinical isolates. S. intermedius was associated with abscesses of the brain and liver, while both S. anginosus and S. constellatus were isolated from a wider range of sites and infections. S. anginosus strains predominated in both genitourinary and gastrointestinal sources and exhibited a wider range of phenotypes, particularly in the ability to ferment mannitol and/or raffinose. PMID- 1734063 TI - Comparison of six different culture media for isolation of Treponema hyodysenteriae. AB - Fecal material from pigs experimentally infected with Treponema hyodysenteriae was collected and inoculated on six different selective media to compare their abilities for recovery of T. hyodysenteriae. Additionally, various types of samples were compared to find the most appropriate for submitting material to laboratories. Isolation rates for T. hyodysenteriae were 89.7% on BJ medium, 88.3% on TSA-BJ medium, 76.6% on SVC medium, 76.6% on BA2-BJ medium, 75.2% on BA2 SVC medium, and 52.4% on TSA-S400 medium. BJ medium was the most useful, yielding good growth of T. hyodysenteriae and inhibition of the normal fecal flora. Also, undiluted fecal material kept at refrigeration temperature allowed better recovery of T. hyodysenteriae during storage than swabs. PMID- 1734064 TI - Phage pattern-specific oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus in U.S. hospitals: epidemiological significance. AB - For a 13-year period (1978 through 1990), oxacillin-resistant (MIC, greater than 4 micrograms/ml) Staphylococcus aureus (ORSA) strains were collected from Clinical Center (National Institutes of Health) patients and patients from five other U.S. hospitals. From Clinical Center patients, 251 of 253 isolates (99%) were bacteriophage typed as phage group III. Five other hospitals contributed 203 ORSA strains, of which 188 (93%) were group III. The group III ORSA strains predominantly included a characteristic core pattern of phages, 7/47/53/54/75/77. For the low-level (borderline) oxacillin-resistant strains (MIC, 2 to 4 micrograms/ml), amoxicillin-clavulanic acid combination (Augmentin) testing disclosed 62 hyper-beta-lactamase producers, of which 59 (95%) were of a separate, distinct S. aureus strain, with the phage pattern 92/94/96/292/D-11 (group V). Thus, ORSA and hyper-beta-lactamase producing S. aureus are distinct epidemic strains. PMID- 1734065 TI - Use of polymerase chain reaction for rapid diagnosis of tuberculosis. AB - A DNA amplification assay using the polymerase chain reaction technique designed for the rapid identification of Mycobacterium bovis organisms was used to test 211 human mycobacterial isolates and 177 clinical specimens previously submitted for routine mycobacterial culture. The procedures described could be used by routine or specialist laboratories for identification of M. tuberculosis complex organisms in 4 h and/or as a rapid screening method for the direct detection of M. tuberculosis complex organisms in specimens. PMID- 1734066 TI - Immune reactivity to fractionated Leishmania aethiopica antigens during coinfection with human immunodeficiency virus type 1. PMID- 1734067 TI - Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes. AB - Polymerase chain reaction (PCR) testing using up to four primer pairs and biotinylated probes was 97.9% sensitive (188 of 192 specimens positive) and 100% specific (267 of 267 specimens negative) for detecting the presence or absence of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells from pediatric patients whose HIV status has been confirmed. SK38/39 and SK145/150 were the most sensitive primer pairs, respectively detecting HIV DNA in 95.6 and 95.9% of peripheral blood mononuclear cell specimens from HIV-infected children and collectively detecting all adequately tested PCR-positive specimens. Primer pairs SK29/30 and SK68/69 respectively detected HIV DNA in only 76.4 and 76.6% of HIV-positive specimens. Among infants born to HIV-seropositive mothers, 30 who subsequently were confirmed to be infected were sampled when they were less than or equal to 6 months of age; in all but one infant, HIV DNA was found in the first specimen collected. Among the nine youngest infected infants tested, all were PCR positive by 38 days of age. PCR methods thus have reliably detected vertically transmitted HIV infection early in life. PMID- 1734068 TI - Optimization and standardization of an enzyme-linked immunosorbent assay protocol for serodiagnosis of Actinobacillus pleuropneumoniae serotype 5. AB - An indirect enzyme-linked immunosorbent assay protocol has been optimized with special emphasis given to assay standardization and quality control. Technical aspects such as choice of a microplate, antigen immobilization, buffer composition, optimal screening dilution of sera, and kinetics of the enzymatic reaction were studied and evaluated in order to design a standard protocol offering maximal analytical sensitivity and specificity, as well as to obtain minimal within- and between-plate variability. Among the 27 plates tested, the Nunc 475-094 and 269-620 immunoplates were found to be the best in terms of high positive-to-negative ratio and low variability. No significant differences in antigen immobilization were found by using buffers of various compositions or pHs; however, the presence of magnesium ions (Mg2+; 0.02 M) resulted in a twofold increase in nonspecific background. An optimal screening dilution of sera was established at 1:200. A 1-h incubation period for test serum was found to be optimal. Maximum enzymatic activity for peroxidase was obtained by adjusting both substrate (H2O2) and hydrogen donor [2,2' -azinobis(3-ethylbenz-thiazoline sulfonic acid)] concentrations to 4 and 1 mM, respectively. To control between plate variability, a timing protocol was adopted. Within-plate variability was also controlled by using a sample placement configuration pattern. Sliding scales were determined by repeated testing of a cross section of samples to set acceptance limits for both within- and between-plate variability. These limits were used in a quality control program to monitor assay performance. The results obtained suggest that this standardized protocol might be useful in the serodiagnosis of Actinobacillus pleuropneumoniae serotype 5. PMID- 1734069 TI - Controlled evaluation of BACTEC PLUS 27 and Roche Septi-Chek anaerobic blood culture bottles. AB - Becton Dickinson Diagnostic Instrument Systems (Sparks, Md.) recently introduced BACTEC high-volume aerobic and anaerobic bottles that accept up to 10 ml of blood for use on their nonradiometric blood culture instruments. Both bottles contain 25 ml of tryptic soy broth, 0.05% sodium polyanetholesulfonate, and mixed resins. We compared the anaerobic bottle, designated BACTEC PLUS 27 (BP27), with the Roche Septi-Chek (RSC) Columbia broth anaerobic bottle in a collaborative evaluation at three university hospitals. A total of 5,152 adequately filled blood cultures were obtained from adult patients with suspected bacteremia or fungemia. Staphylococcus aureus was recovered significantly more often (P less than 0.03) from BP27 bottles alone; there were no other significant differences in yield. When microorganisms were recovered from both anaerobic bottles, growth was detected earlier in BP27 than it was in RSC (P less than 0.001), especially for S. aureus (P less than 0.001) and Staphylococcus epidermidis (P less than 0.02). We conclude that the yield from BP27 bottles is equivalent to or better (S. aureus) than that from RSC anaerobic bottles with Columbia broth and that speed of detection is superior with BP27 bottles. PMID- 1734070 TI - Differentiation of Giardia duodenalis from other Giardia spp. by using polymerase chain reaction and gene probes. AB - Giardia spp. are waterborne organisms that are the most commonly identified pathogenic intestinal protozoans in the United States. Current detection techniques for Giardia species in water include microscopy and immunofluorescence techniques. Species of the genus Giardia are classified on the basis of taxonomic criteria, such as cell morphology, and on host specificity. We have developed a polymerase chain reaction- and gene probe-based detection system specific for Giardia spp., which can discriminate between the relevant species of the G. duodenalis type pathogenic to humans and other Giardia species that are not human pathogens. This method can detect a single Giardia cyst and is therefore sensitive enough for environmental monitoring. PMID- 1734071 TI - Evaluation of MicroScan Rapid Pos Combo panels for identification of staphylococci. AB - MicroScan Rapid Pos Combo panels (Baxter Diagnostics, Inc., MicroScan, West Sacramento, Calif.) contain substrates conjugated with fluorophores and substrates with a fluorescent pH indicator. AutoSCAn W/A, an automated panel processor equipped with a fluorometer, reads the panels after 2 h of incubation and can identify staphylococci to the species level. We tested 239 strains belonging to 17 species of staphylococci. All the strains were identified by conventional methods (W.E. Kloos and K.H. Schleifer, J. Clin. Microbiol. 1:82-88, 1975) and by the MicroScan Rapid ID system. The system correctly identified 219 (91.6%) strains; nine (3.8%) identification results were probably correct, and six (2.5%) results were incorrect. The system designated five (2.1%) strains as rare biotypes. The automated MicroScan Rapid ID system is useful and reliable in identifying most human isolates of staphylococci encountered in the clinical laboratory. PMID- 1734072 TI - Diagnosis of Helicobacter pylori infection in adult and pediatric patients by using Pyloriset, a rapid latex agglutination test. AB - Pyloriset (Orion Diagnostica, Espoo, Finland) is a rapid antibody test using latex particles coated with acid-extracted antigen of Helicobacter pylori. We evaluated its ability to predict infection in 100 adult patients and 50 pediatric patients referred for gastric endoscopy. Sixty of 65 H. pylori-infected adults were correctly identified by the test. There were 12 false-positive and 5 false negative reactions seen. Pyloriset had a sensitivity of 92% and a specificity of 66%. The positive predictive value was 83% and the negative predictive value 82%. In contrast, sensitivity dropped to 36% in the pediatric patients and the positive predictive value was only 40%. Pyloriset could become an important alternative to other more time-consuming diagnostic tests for H. pylori-infected adult patients but is inadequate for diagnosis of pediatric H. pylori infection. PMID- 1734073 TI - Polymerase chain reaction primers and probes derived from flagellin gene sequences for specific detection of the agents of Lyme disease and North American relapsing fever. AB - By cloning and sequencing the flagellin gene of Borrelia hermsii and comparing this sequence with that of the corresponding gene from B. burgdorferi, I identified a central region within the two genes which showed a reduced level of sequence similarity. Oligonucleotide sequences selected from this region produced species-specific amplimers when used in polymerase chain reaction experiments. Thus, primers derived from the B. burgdorferi sequence amplified a 276-bp fragment from 22 strains of B. burgdorferi of diverse geographic origin but not from 5 strains of B. hermsii, 5 other Borrelia species, 16 Treponema, Leptospira, and Spirochaeta species, or representatives of 10 other bacterial genera. However, when the amplified fragments were tested for hybridization with an oligonucleotide probe derived from the nonhomologous region, seven strains from either Germany or Switzerland did not hybridize. Cloning and sequencing of the amplified fragments from these strains revealed that the 22 strains of B. burgdorferi tested could be divided into three groups based on the nucleic acid sequence of the central region of the flagellin gene. With this information, oligonucleotide probes that hybridized to the amplified fragments and were able to differentiate the three groups of B. burgdorferi were designed. The corresponding primers, derived from the B. hermsii gene sequence, were tested for their ability to amplify DNA from this collection of strains. Although no amplification was obtained with representatives of the three groups of B. burgdorferi or various Treponema, Leptospira, and Spirochaeta species, amplification was obtained with the five other Borrelia species (B. parkeri, B. turicatae, B. crocidurae, B. anserina, and B. coriaceae) in addition to the five strains of B. hermsii. Sequencing of the amplified fragments from one strain of B. hermsii as well as B. parkeri and B. turicatae allowed the design of oligonucleotide probes that were able to differentiate the three species of North American relapsing fever spirochetes into two separate groups. These studies suggest that there is sufficient diversity within the flagellin gene sequences of closely related Borrelia species to differentiate them into groups and to pursue taxonomic studies both within and between species. PMID- 1734074 TI - Di-n-pentyl phthalate-induced inflammatory changes in the rat testis are accompanied by local production of a novel lymphocyte activating factor. AB - Phthalate esters (PAE) are plasticizers in polyvinyl chloride plastics used, for example, in package material for medical solutions. PAE exposure is associated with testicular damage that primarily affects Sertoli cells, and is concomitant with leukocyte infiltration into the testicular interstitium. We have demonstrated that the rat testis constitutively produces a lymphocyte activating factor (LAF) resembling interleukin-1 alpha, and originating from Sertoli cells. The testicular interleukin-1-like factor (tIL-1) has a relative molecular mass (Mr) of 17,000 (17 k) and an isoelectric point (pI) of 5.7. In the present study we have measured testicular LAF activity after exposure to di-n-pentyl phthalate (DPP) in 40-day-old rats. We found a large increase in LAF bioactivity which was evident already 3 h after a single oral dose of DPP. The increase was maximal 9 12 h after exposure, and had decreased toward the control level at 24 h. The increased activity was found to be at least partly due to the induction of a novel LAF with Mr 38,000 and pI 4.5. Morphological examination confirmed earlier results with an interstitial leukocyte infiltration 6 h after DPP exposure. The identity of the novel LAF and its functional relation to testicular inflammation remain to be established. PMID- 1734075 TI - Preferential mammary storage and secretion of immunoglobulin gamma (IgG) subclasses in swine. AB - Levels of three immunoglobulin gamma (IgG) subclasses, IgGA, IgGB and IgGC, were measured in sow sera, mammary glands, colostrum and milk samples by the single radial immunodiffusion. Serum IgGA and IgGB levels, but not IgGC, showed time dependent variations during gestation and lactation periods. The IgGA level started to decline at day 106 of gestation, reached its minimum at farrowing, and returned to the pre-gestation level 1-3 weeks after weaning. The serum IgGB level started to decrease at day 111 of gestation, reached its minimum at farrowing, and returned to the initial gestation level 1 week after farrowing. A notable decrease (P less than 0.1) in serum IgGC level was observed only on the day of farrowing. IgGA and IgGB were preferentially stored in mammary glands of full term pregnant sows and secreted into colostrum after farrowing. In contrast, relatively small amounts of IgGC were stored in the mammary glands and secreted into colostrum. These data are interpreted as an indication that the preferential storage of IgGA and IgGB in the mammary gland of sows occurs at the time of significant decreases of these two IgG subclasses in the sera during late gestation and early lactation. PMID- 1734076 TI - The cellular immune response to immunization with zona pellucida antigens. AB - The cellular immune response of mice to porcine and rat zona pellucida and cynomolgus macaques to porcine zona pellucida antigens was evaluated. Mice mounted a vigorous cellular response to both antigens, as determined by the T cell proliferation response in vitro. There was poor cross-reactivity to murine zonae by T cells or serum antibodies from mice immunized with rat zona pellucida. Nevertheless, ovaries from the mice immunized with rat zona had significantly fewer antral follicles than adjuvant-treated controls, suggesting that the immune response to the zona antigen disrupted follicular development. T cells from two macaques that had been immunized with porcine zona pelludica proteins proliferated in vitro in response to this antigen. Both macaques also had strong antibody responses. The patterns of urinary steroid metabolites in these animals provided clear evidence of ovarian malfunction following immunization. The data indicate that a significant cellular immune response is generated upon immunization of animals with zona pellucida antigens regardless of whether the antigens are cross reactive with the host zona antigens. Whether impaired ovarian function and follicular development are related to the cellular response must be determined in future studies. PMID- 1734077 TI - Pregnancy-associated major basic protein in amniotic fluid. AB - The pregnancy-associated major basic protein, a protein elevated in the sera of all pregnant women, is virtually identical to the eosinophil granule major basic protein. To determine whether pregnancy-associated major basic protein is present in amniotic fluid, we examined samples from both early and late gestation by a double antibody radioimmunoassay. A total of 112 amniotic fluids were tested and all but three contained levels of pregnancy-associated major basic protein greater than 400 ng/ml. Amniotic fluid pregnancy-associated major basic protein antigenic activity was immunochemically identical to that of the eosinophil granule major basic protein and also had identical physicochemical properties such as heat stability and the need for reduction and alkylation. Although the majority of amniotic fluid samples (90 of 112) were obtained from healthy women with normal gestations, the remaining 21 amniotic fluid samples were from women with Rh sensitization and from one gestation complicated by intrauterine growth retardation. PMID- 1734078 TI - Bovine early pregnancy factor (EPF) activity dependent on a 67-kDa polypeptide. AB - Maternal bovine EPF activity can be reduced to one single polypeptide enriched and identified from serum of cows in early pregnancy. The relative molecular weight of this active polypeptide was estimated at 67 kDa. This bovine EPF was labelled by 125I and peroxidase. In parallel investigations of non-pregnant animals a 67-kDa polypeptide was additionally identified in the last purification step, but without EPF activity in the rosette inhibition test. This indicated occurrence of an inactive pre-compound (or carrier protein) of the EPF in the non pregnant state. On pre-incubation of lymphocytes with EPF analogues (inactive polypeptide from nonpregnancy serum) EPF retained its optimal activity, its lymphocyte receptors being unaffected. Monoclonal antibodies produced against HPLC-enriched EPF were reactive to the 67-kDa polypeptide in pregnancy material as well as in nonpregnancy material and were not able to differentiate between 'pregnant' and 'nonpregnant'. A mouse anti-EPF serum produced against highly purified EPF isolated from SDS PAGE showed reactivity only against the 67-kDa polypeptide of pregnancy serum but not against that of non-pregnancy serum. This is the first evidence for a difference in antigenic determinants of the two 67 kDa proteins found in pregnancy and non-pregnancy serum. Furthermore, a second higher molecular weight protein could be identified by this antiserum in pregnancy and non-pregnancy serum. PMID- 1734079 TI - Isolation and characterisation of a subpopulation of human chorionic cytotrophoblast using a monoclonal anti-trophoblast antibody (NDOG2) in flow cytometry. AB - Human cytotrophoblast cells, isolated from term amniochorion by enzymic digestion and Percoll gradient centrifugation, were characterised by flow cytometry. A panel of 12 anti-trophoblast monoclonal antibodies was screened for labelling of these cells in flow cytometry and the results compared with immunoperoxidase labelling of cytospin preparations and tissue sections. All 12 antibodies were positive for trophoblast on tissue sections, 11/12 were positive on cytospins but only two (NDOG2 and GB25) gave consistent results in flow cytometry. Two-colour labelling with NDOG2 and W6/32, an antibody to HLA-A, -B, -C, demonstrated that 88% of the NDOG2-positive cells also express Class I major histocompatibility complex (MHC) antigens. The NDOG2-positive cytotrophoblast subpopulation was isolated by flow cytometry in sufficient purity (greater than 95%) and yield (3.1 x 10(6)) for use in functional studies in vitro. PMID- 1734080 TI - PGE2-independent immunosuppressive activity of horse trophoblast tissue. AB - It has been proposed that PGE2 is an important immunosuppressant acting at the fetal-maternal interface during pregnancy. We have previously shown that horse conceptus-conditioned medium suppresses lymphocyte proliferation. This experiment was designed to determine if horse conceptus-derived immunosuppressive activity could be attributed to PGE2 production by the trophoblast tissue. Trophoblast tissue from 21-day-old conceptuses was cut into equal sections and cultured in the presence or absence of the prostaglandin inhibitor, indomethacin. Following culture, immunosuppressive activity and the concentration of PGE2 were determined for each sample of both horse-trophoblast conditioned medium (HTCM) and indomethacin-treated HTCM (I-HTCM). Suppressive activity was identified in lymphocyte proliferation assays via reduced [3H]thymidine uptake by pokeweed mitogen stimulated horse lymphocytes. A radioimmunoassay was used to quantify PGE2. While PGE2 production was greatly reduced in cultures containing indomethacin, trophoblast-derived immunosuppressive activity was not affected. These data indicate that PGE2 is not the primary immunosuppressant produced by horse trophoblast tissue. PMID- 1734081 TI - Active cancer therapy combining 13-cis-retinoic acid with interferon-alpha. PMID- 1734082 TI - Anti-metastasis drug ready for human trials. PMID- 1734083 TI - Consensus on early melanoma: less surgery, fewer tests. PMID- 1734084 TI - 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. AB - BACKGROUND: Retinoids (vitamin A derivatives) and interferon-alpha (IFN-alpha) are potent regulators of malignant cell differentiation and proliferation, and both have immunomodulatory and antiangiogenesis activity. A large body of preclinical and clinical data supports the use of combination therapy with 13-cis retinoic acid (13-cRA) and IFN-alpha in patients with squamous cell carcinoma of the skin. This carcinoma is an extremely common and frequently severely disfiguring cancer, for which about 10% of patients remain uncured following standard local therapy. PURPOSE: Our purpose was to test whether a 20% or greater complete response rate could be achieved using a combination of these two agents in patients with advanced squamous cell carcinoma of the skin in whom local therapy had failed or was unfeasible or who had regional and/or distant metastases. METHODS: Thirty-two patients with heavily pretreated, advanced inoperable cutaneous squamous cell carcinoma of the skin were given a combination of oral 13-cRA (1 mg/kg per day) and subcutaneous recombinant human IFN alpha-2a (3 million units per day) for at least 2 months, unless disease progressed earlier, in a phase II trial. RESULTS: Nineteen (68%) of the 28 assessable patients responded, seven (25%) of whom had complete responses. Response rates were 93% (13 of 14) in patients with advanced local disease (six complete responses), 67% (four of six) in patients with regional disease (no complete responses), and 25% (two of eight) in patients with distant metastases (one complete response). The relationship between decreased response rate and increased extent of disease was highly statistically significant (P less than .005, chi-square test). The median response duration was greater than 5 months. No life-threatening toxic effects occurred in assessable patients treated with this combination, although dose reductions were required in 18 patients. The major limiting side effect in this elderly patient population (median age, 67 years) was cumulative fatigue. CONCLUSION: These results indicate that combined systemic therapy with 13-cRA and IFN alpha-2a is highly effective in patients with advanced squamous cell carcinoma of the skin. PMID- 1734085 TI - 13-cis-retinoic acid plus interferon alpha-2a: highly active systemic therapy for squamous cell carcinoma of the cervix. AB - BACKGROUND: Chemotherapeutic study of cervical squamous cell carcinoma has shown some positive results. Complete plus partial (overall) response rates of 15%-35% (complete response rate, less than 5%) were achieved with the use of a small number of cytotoxic single agents in patients with advanced disease. In addition, overall response rates of 60%-70% (complete response rates, 10%-20%) were achieved with cisplatin-based, multiagent regimens in patients with primary, locally advanced disease. However, the lack of clear evidence that existing chemotherapy can achieve a survival benefit, coupled with the worldwide annual deaths of hundreds of thousands of women from cervical cancer, indicates the urgent need for effective systemic therapy for this disease. PURPOSE: In view of the preclinical and clinical evidence that supports testing of the novel combination of 13-cis-retinoic acid (13-cRA) plus interferon-alpha (IFN-alpha) in cervical squamous cell carcinoma, we conducted a phase II study of this regimen in locally advanced disease. METHODS: Twenty-six patients with untreated, locally advanced squamous cell carcinoma of the cervix were treated daily for at least 2 months with oral 13-cRA (1 mg/kg) and subcutaneous recombinant human IFN alpha-2a (6 million units). In 21 patients (81%), the disease was stage II or higher. RESULTS: Thirteen patients (50%) experienced major responses (tumor regression greater than or equal to 50%) in association with resolution of symptoms; one achieved complete response, and 12 experienced partial response. Seven with partial response are improving further, four are being maintained in partial response, and one responder has relapsed during therapy. The response rate is 58% (11 of 19) in patients with stage IIB or higher disease and 66% (10 of 15) in patients with bulky disease (at least one dimension greater than or equal to 10 cm). Of the 13 non-responders, nine have stable disease and four have had disease progression during therapy. Toxicity was minimal. CONCLUSION: These preliminary results indicate that systemic 13-cRA plus IFN alpha-2a is a highly active, well tolerated therapy for locally advanced cervical cancer. PMID- 1734086 TI - Pattern of p53 gene mutations in breast cancers of women of the midwestern United States. AB - BACKGROUND: Mutation in the p53 gene is the most common genetic lesion in human cancers. The pattern of mutation in the p53 gene differs among cancers and may be a useful epidemiological tool for identification of factors contributing to carcinogenesis. PURPOSE: Our purpose was to determine if the pattern of p53 mutation in breast carcinomas in our population of women residing in the midwestern region of the United States is similar to the pattern of p53 mutation in breast cancers in patients from other regions of the United States and Europe and in other epithelial tumors. METHODS: With a technique we recently developed for the analysis of p53 mutations in genomic DNA from tumor cell clusters in touch preparations of solid tumors, we sequenced exons 5-9 and adjacent splice junctions of the gene in 44 breast cancers. Cells from each tumor were also stained with three monoclonal antibodies which recognize different epitopes of the p53 protein. RESULTS: We detected p53 mutations in 14 (32.6%) of 44 breast carcinomas. Only half of the mutations were missense changes. The other half included five microdeletions (three producing frame-shifts), one single-base substitution generating a stop codon, and one single-base substitution generating a splice junction abnormality. Nuclear expression of p53 antigen was present in eight of 44 cancers, including six with hemizygous missense mutations in the p53 gene. CONCLUSIONS: The pattern of p53 mutations in our breast cancer population differs from that reported in breast cancer populations by other investigators in which most p53 mutations were missense. Among 14 mutations in our population, at least five drastically altered the structure of p53, suggesting that a recessive mechanism of inactivation of the p53 gene may be more common than in other populations. IMPLICATIONS: Differences in the pattern of p53 mutation in breast cancers in Midwestern women and in breast cancers in other populations may reflect selection bias or small sample sizes currently available. However, our data are compatible with the possibility that an endogenous or exogenous factor influences p53 carcinogenesis in some women with breast cancer in the Midwest to a greater extent than in other regions of the United States and Europe. PMID- 1734087 TI - Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. AB - BACKGROUND: Our current protocol for treatment of childhood acute lymphoblastic leukemia (ALL) was designed to assess the efficacy of methotrexate (MTX) plus L asparaginase and of etopisode (VP-16) plus cytarabine (ARA-C) during intensive consolidation and continuation therapies and to determine the feasibility of intensifying MTX therapy by the use of divided oral doses of MTX. The protocol was associated with unexpected acute neurotoxicity. There are few reports of such toxic effects during therapy for ALL. PURPOSE: This report describes these toxic effects and outlines our successful approach to the problem. METHODS: The standard four-drug induction regimen consisted of vincristine, L-asparaginase, daunorubicin, and prednisone. In consolidation therapy, oral MTX was given in divided doses (dMTX) of 25 mg/m2 every 6 hours four times daily in four weekly courses concomitant with weekly triple intrathecal therapy--MTX, ARA-C, and hydrocortisone--plus one dose of leucovorin 24 hours after triple intrathecal therapy. Consolidation treatment ended with three daily doses of intravenous VP 16 and ARA-C. The first 16 months of continuation therapy included 6-week cycles of dMTX and L-asparaginase, both given every other week for 5 weeks, with 6 mercaptopurine nightly, and then two doses of VP-16 plus ARA-C and one dose of triple intrathecal therapy. RESULTS: Twenty-five of the 138 patients evaluated had acute neurotoxicity. Ten of the first 72 experienced a seizure or episode of transient neurological deficit 9-11 days following the administration of intravenous ARA-C, VP-16, and triple intrathecal therapy. Despite discontinuation of intrathecal ARA-C, which eliminated simultaneous intravenous and intrathecal treatment with ARA-C, acute neurotoxicity was observed in six previously unaffected patients and six of 42 patients treated after the elimination of intrathecal ARA-C. Therefore, as a second amendment, oral leucovorin was given 24 and 36 hours after dMTX and intrathecal MTX in continuation therapy. No acute neurotoxicity has been seen in 24 patients subsequently entered in the study. CONCLUSION: These findings suggest that folate replacement due to administration of leucovorin modulated MTX toxicity and/or modified an interaction among VP-16, ARA-C, intrathecal therapy, and the central nervous system. PMID- 1734088 TI - Depletion of glutathione in normal and malignant human cells in vivo by buthionine sulfoximine: clinical and biochemical results. PMID- 1734089 TI - Canine malignant lymphoma and 2,4-dichlorophenoxyacetic acid herbicides. PMID- 1734090 TI - Antimicrobial treatment of the umbilical cord. PMID- 1734091 TI - Persistent tympanic membrane perforation from ventilation tubes. PMID- 1734092 TI - New forms and new needs may make macrolides antibiotics of the decade. PMID- 1734093 TI - From the Centers for Disease Control. Surgeon General's Conference on Agriculture. PMID- 1734094 TI - From the Centers for Disease Control. Hysterectomy prevalence, cervical cancer deaths. PMID- 1734095 TI - A piece of my mind. Keeping up with the literature. PMID- 1734096 TI - Radiation dosage estimation and health risk. PMID- 1734097 TI - Reporting negative studies in the mass media. PMID- 1734098 TI - Reporting negative studies in the mass media. PMID- 1734099 TI - Tuberculous pericarditis. PMID- 1734100 TI - Tuberculosis screening and indications for preventive therapy. PMID- 1734101 TI - CABG surgical mortality in different centers. PMID- 1734102 TI - Free clinics and malpractice claims. PMID- 1734103 TI - A modest proposal: a vow of chastity for single physicians in remote areas? PMID- 1734104 TI - Glove tears and sharp injuries in surgical personnel. PMID- 1734105 TI - Improving growth status of Asian refugee children in the United States. AB - OBJECTIVE: To analyze the trend and pattern of the nutrition status of Southeast Asian refugee children and other low-income children in the United States. DESIGN: Descriptive analysis of the growth data from the Pediatric Nutrition Surveillance System of the Centers for Disease Control, Atlanta, Ga, from 1980 through 1989. SUBJECTS: Children under 5 years of age from low-income families enrolled in public health clinics in 12 selected states. MEASUREMENTS AND MAIN RESULTS: Asian refugee children experienced a progressive and significant decline in the prevalence of low birth weight, low height-for-age, and low weight-for age, while these nutritional indexes remained stable for low-income white, black, and Hispanic children. By 1989, the growth status of Asian children was near that of other ethnic groups. CONCLUSIONS: The marked improvement of growth status among Asian refugee children over a short period suggests that the poor growth status often observed among recently immigrated Asian children is primarily related to nutritional and health factors, rather than genetic factors. In assessing the growth of Asian or immigrant children, it would be helpful to take their family and early childhood background into account. PMID- 1734106 TI - A prospective study of benign breast disease and the risk of breast cancer. AB - OBJECTIVE: To examine the relation between proliferative benign breast disease with and without atypical hyperplasia and the subsequent risk of breast cancer. DESIGN: Case-control study nested within a prospective cohort study. Median follow-up after breast biopsy was 8 years (25th to 75th percentile, 5 to 14 years). PARTICIPANTS: Selected from a prospective cohort of 121,700 US registered nurses followed up from 1976 to 1986. Cases were women with breast cancer who had a prior biopsy for benign breast disease. Controls were randomly selected and matched on year of biopsy and year of birth from among women in the cohort who had a benign breast biopsy but who did not develop breast cancer. Included in the analysis were 121 cases and 488 controls. MAIN OUTCOME MEASURE: Development of breast cancer. RESULTS: Slides from the first benign breast biopsy were reviewed by two breast pathologists blinded to the outcome. The multiply adjusted relative risks (RRs) for breast cancer, relative to women with no proliferative disease, were 1.6 for proliferative disease without atypia (95% confidence interval [Cl], 1.0 to 2.5) and 3.7 for atypical hyperplasia (95% Cl, 2.1 to 6.8). Breast cancer risk was more strongly associated with atypical hyperplasia among premenopausal women (RR = 5.9; 95% Cl, 2.9 to 13.2) than postmenopausal women (RR = 2.3; 95% Cl, 0.9 to 5.9), but the association of breast cancer risk with proliferative disease without atypia did not differ across menopausal status. CONCLUSION: These results confirm the marked increase in breast cancer risk among women with atypical hyperplasia, particularly in premenopausal women, and suggest that these women should be encouraged to undergo frequent breast cancer screening. PMID- 1734107 TI - Reducing the number of uninsured by subsidizing employment-based health insurance. Results from a pilot study. AB - OBJECTIVE: To evaluate whether employers who do not provide health insurance would offer such benefits after a 50% reduction in the price of health insurance. DESIGN: Using a survey of 530 firms at two sites in New York State, we estimate the number of firms that added insurance during 1988 as a percentage of firms that were eligible for the subsidy. We use this proportion as an estimate for the number of firms that would have added insurance in the absence of the subsidy program. We then estimate the number of firms adding insurance during the initial year of the program, 1989. SETTING: The subsidized health insurance pilot projects were available in Brooklyn and in the Albany-Plattsburgh-Poughkeepsie region of New York State. INTERVENTION: New York State subsidized the price of health insurance, reducing it by 50%. Eligible employers were responsible for paying the remaining portion of the premium. RESULTS: The subsidized health insurance products increased the number of small firms (under 20 employees) offering insurance by a small amount, approximately a 3.5 percentage point increase. When fully implemented and assuming all eligible employers were aware of the program, the subsidy would increase the proportion of firms offering insurance by 16.5 percentage points. We view this as an upper boundary. CONCLUSIONS: Increased program visibility and allowing the employee to share in the premium payment may increase the number of employers offering insurance. Even under ideal conditions, however, the results highlight the limitations of voluntary programs to increase the number of employers offering health insurance. PMID- 1734108 TI - The challenge of minority recruitment in clinical trials for AIDS. PMID- 1734109 TI - The reliability of peer assessments of quality of care. AB - OBJECTIVE: To critically examine the literature regarding the interreviewer reliability of the standard practice of peer assessment of quality of care. DATA SOURCES: Computerized searches of the English-language literature from 1966 through 1990 using MEDLINE, HEALTHLINE, and SCISEARCH databases were performed to identify studies reporting data on interreviewer agreement of implicit evaluations of patient care episodes. STUDY SELECTION: Seventeen studies were identified. Five studies were excluded from this review because of deficiencies in the methods or lack of data on chance-corrected indexes of agreement. DATA EXTRACTION SYNTHESIS: The degree of agreement beyond chance was compared with accepted standards in the 12 remaining studies. Most of these studies found agreement corrected for chance to be in the range regarded as poor, indicating that physician agreement regarding quality of care is only slightly better than the level expected by chance. CONCLUSIONS: Given the magnitude of the resources devoted to quality assurance and the centrality of peer assessment to these efforts, there is a need for a global reexamination of the peer review process. A number of proposals appear to have potential for improving the peer review process including more objective assessment procedures, multiple reviewers, higher standards for reviewers, elimination of systematic reviewer bias, use of outcome judgements, and adoption of practice guidelines. PMID- 1734111 TI - An investigator's journey in cardiology. PMID- 1734110 TI - Secondary dyslipidemia. Inadvertent effects of drugs in clinical practice. AB - OBJECTIVE: To examine the available literature on commonly prescribed drugs and their effects on blood lipid and lipoprotein levels. DATA SOURCES: The review was based on searches of English-language articles from 1975 to 1990 by Medlars II and MEDLINE programs, the Index Medicus for 1980 to 1990, and references from identified articles. Relevant journals published within the last 6 months were also examined. STUDY SELECTION: More than 500 articles were identified for inclusion. Articles were selected on the basis of appropriateness of design to demonstrate significant results, determined by consensus when necessary. DATA EXTRACTION: Studies were classified according to type (observational or interventional), length of follow-up, and type of controls. Quanitative analysis of lipid, lipoprotein, and apoprotein changes induced by drugs was computed as the percentage of change observed during the course of the study (interventional) or compared with the controls at a given time (observational). DATA SYNTHESIS: Steroid hormones that have strong progestogenic and androgenic properties, retinoids, cyclosporine A, and phenothiazines are potentially atherogenic. Steroid hormones with dominant estrogenic properties, several anticonvulsants, biguanides, high-dose ketoconazole, and aminosalicylic acid are potentially antiatherogenic. Corticosteroids appear to elevate all the lipoprotein cholesterol levels. Oral estrogens, retinoids, and corticosteroids also can elevate triglyceride levels. Other drugs with questionable effects on lipoprotein metabolism are reviewed. CONCLUSION: Although the long-term implications of drug induced lipoprotein changes are still undefined, physicians need to consider these effects in clinical practice. PMID- 1734112 TI - On the utility of growth curves. PMID- 1734113 TI - Public opinion and AIDS. Lessons for the second decade. PMID- 1734114 TI - Dr Mudd, the grandson, fights to clear name of famed ancestor. PMID- 1734115 TI - Clinical and metabolic characteristics of diabetic ketoacidosis. PMID- 1734116 TI - Management of complex perineal injury. PMID- 1734117 TI - An unusual cause of hypertension. PMID- 1734118 TI - False sense of security. PMID- 1734119 TI - Medical education: behind the lectern. PMID- 1734120 TI - Patient relations guidelines: keeping your schedule running smoothly to minimize the waiting game. TMA Communications and Public Service Committee. PMID- 1734121 TI - On the other end... PMID- 1734122 TI - Organ transplantation in Tennessee 1989-1990. Report of the Tennessee Transplant Society and the TMA Committee on Organ Procurement. PMID- 1734123 TI - [Sweden and Great Britain. Internal market is introduced into health care. Independence of the medical profession is challenged]. PMID- 1734124 TI - [Coronary vessel radiography--further decentralization is necessary, safe and feasible]. PMID- 1734125 TI - [Studies of prescriptions--a starting-point for scientific work]. PMID- 1734126 TI - [Drug companies have to find new indications for ACE inhibitors]. PMID- 1734127 TI - [Organizational change at a surgery department increased productivity]. PMID- 1734128 TI - [A regional center for adverse effects in Umea will stimulate increased reporting]. PMID- 1734129 TI - [Complications of coronary vessel radiography--a Swedish study compared with international results]. PMID- 1734130 TI - [The number of psychiatric commitments is decreasing but more and more patients appeal]. PMID- 1734131 TI - [Fish-scale and algae become biosensors. Hunting for a biocompatible blood glucose sensor]. PMID- 1734132 TI - [Drug control within the EEC I: coordination during the 1990's]. PMID- 1734133 TI - [Insult to psychiatry]. PMID- 1734134 TI - [Gene therapy soon in clinical use but major problems remain unsolved]. PMID- 1734135 TI - [Exposure to gasoline and leukemia: a small risk for many]. PMID- 1734136 TI - [Should active euthanasia reduce confidence of the public in health care services?]. PMID- 1734137 TI - [The patient insurance's injury registry: feedback of experiences to the health care services has a preventive effect]. PMID- 1734138 TI - [Cephalosporins--a common cause of nosocomial Clostridium difficile diarrhea]. PMID- 1734139 TI - [Strongly increased risk of acute myeloid leukemia among gasoline service station workers]. PMID- 1734140 TI - [Autoantibodies as serological markers in the diagnosis of glomerulonephritis]. AB - Autoimmunity is now regarded as the unequivocally predominant pathogenic process underlying most forms of primary and secondary glomerulonephritis in humans, and a number of autoantibodies occurring in conjunction with glomerulonephritis have been discovered. However, apart from the anti-NC1 antibodies occurring in classic Goodpasture's syndrome, the exact pathogenic role of these autoantibodies in human glomerulonephritis remains to be established, though this in no way diminishes the importance of their study. They have been of enormous value in subclassifying glomerulonephritis, previously thought to be a homogeneous entity. Autoantibody analysis has become a vital aid in the early diagnosis of rapidly progressive glomerulonephritis, which in turn has enabled treatment to be started early, thus contributing to a decline in the morbidity and mortality resulting from these disorders. Moreover, investigation of these autoantibodies will be of immense value in future studies focused on the pathogenic mechanisms involved in glomerulonephritis. PMID- 1734141 TI - [What happens with the ear in temporal bone fractures?]. PMID- 1734142 TI - [Medical technology facing the 21st century--industrial methods headed for clinical practice]. PMID- 1734143 TI - [Warning against wrongly labelled implants. Neglected follow-up in Sweden]. PMID- 1734144 TI - [Acanthamoeba keratitis--a new diagnosis in Sweden]. PMID- 1734145 TI - [50 obstetric malpractice cases: difficult to draw limits, inconsistent decisions]. PMID- 1734146 TI - [Comments on the rules for physicians III]. PMID- 1734147 TI - [Drug control within the EEC II: good possibilities for Sweden]. PMID- 1734148 TI - [Is screening for ovarian cancer beneficial?]. PMID- 1734149 TI - [Advantages and disadvantages of parenteral nutrition]. PMID- 1734150 TI - [Debatable questions on Clostridium difficile diarrhea]. PMID- 1734151 TI - [Wrong conclusions on sick-listing after changing the amalgam fillings]. PMID- 1734152 TI - [Infant-friendly hospitals save millions of lives]. PMID- 1734153 TI - [A study in Fagersta: extensive anticoagulant therapy. High incidence of hemorrhagic complications]. PMID- 1734154 TI - [The woman behind the syndrome. Lucja Frey. Famous for her description of gustatory facial sweating]. PMID- 1734155 TI - [Iatrogenic superior vena cava syndrome. Successful thrombolysis with recombinant tissue plasminogen activator (r-tPA)]. PMID- 1734156 TI - [The dynamic view in psychiatry should get more space in Swedish education and care]. PMID- 1734157 TI - MK801 antagonism of the prolonged depletion of striatal dopamine by amphetamine in iprindole-treated rats. AB - The administration of amphetamine to rats pretreated with iprindole to inhibit the metabolism of amphetamine results in a long-lasting depletion of striatal dopamine and its metabolites, DOPAC and HVA. Pretreatment with MK801, a noncompetitive antagonist of the NMDA (N-methyl-D-aspartate) subclass of excitatory amino acid receptors, antagonized the depletion of striatal dopamine, DOPAC and HVA 3 days after a single dose of amphetamine in iprindole-treated rats. MK801 pretreatment was effective up to 4 hours but not at 8 or 24 hours in preventing amphetamine effects on striatal dopamine, DOPAC and HVA. PMID- 1734158 TI - Nitric oxide control of steroidogenesis: endocrine effects of NG-nitro-L-arginine and comparisons to alcohol. AB - Recent studies suggest that nitric oxide (NO) may regulate hormone biosynthesis and secretion. This was tested by treating male rats with NG-nitro-L-arginine methyl ester (NAME), a NO synthase inhibitor, and measuring serum and testicular interstitial fluid testosterone and serum corticosterone, luteinizing hormone (LH), and prolactin (PRL). The effect of NG-nitro-L-arginine (NA), a less-soluble form of the same NO synthase inhibitor, on the reproductive suppressant actions of alcohol was also examined. NAME increased testosterone and corticosterone secretion dose-dependently without affecting LH and PRL secretion. The alcohol induced suppression of testosterone or LH secretion was not altered by treatment with NA. Although effects of NAME and NA on other systems may be involved, these results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol. PMID- 1734159 TI - Immunohistochemical labeling of androgen receptors in the brain of rat and monkey. AB - Androgen receptor antibodies have recently been developed using fusion proteins containing fragments of human prostatic androgen receptor. We have used a polyclonal antibody raised in rabbits to label androgen receptors in brain sections from male and female rats and monkeys. Free-floating frozen sections were incubated in primary antibody, and processed by the peroxidase-avidin-biotin complex method using biotinylated anti-rabbit IgG. Nickel intensified diaminobenzidine was used as the chromagen, and neurons were labeled in the amygdala, hippocampus, bed nucleus of stria terminalis, septum, preoptic area, in several hypothalamic nuclei including the supraoptic and paraventricular nuclei, in several brain stem motor nuclei and in cerebral cortex. Staining was most intense in cell nuclei but also occurred in cytoplasm and in some neuronal processes. Labeling was more restricted in monkey than in rat brain. Omitting the primary antibody or pre-incubating the primary antibody with rat prostatic cytosol for control purposes demonstrated the specificity of staining. PMID- 1734160 TI - Stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a pressor response with bradycardia. AB - The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. Intrahippocampal injection of neostigmine stimulated the secretion of epinephrine and norepinephrine. Adrenodemedullation did not suppress the increase in blood pressure and the decrease in heart rate. It is concluded that the stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a hypertensive response via an increase in sympathetic drive to the heart and peripheral vasculature, with bradycardia possibly mediated via the parasympathetic system. PMID- 1734161 TI - 'Normal' cigarette smoking increases free cortisol in habitual smokers. AB - In habitual smokers salivary cortisol responses to cigarette smoking were investigated. In the first study, 31 adults assigned to two experimental groups smoked either one or two cigarettes of their preferred brand. Mean salivary cortisol levels were significantly elevated after smoking of two cigarettes. In the second study, 10 smokers and 10 nonsmokers provided saliva samples at 20 min intervals over a 12-hr period. While environmental stimuli were paralleled in both groups overall cortisol output was significantly elevated in the smokers. These data suggest that 'normal' cigarette smoking can increase free cortisol levels. PMID- 1734162 TI - Binding of 3H-gossypol in organelles of cultured bovine luteal cells. AB - Gossypol is an antifertility agent which inhibits steroidogenesis in both sexes. The present study investigated the binding of gossypol in organelles of cultured bovine luteal cell to elucidate its inhibitory site of action in steroid biosynthesis. Cultured bovine luteal cells were incubated with 3H-gossypol (4.3 or 2.15 microM) for 3 hours. At the end of treatment, cultured bovine luteal cells were harvested, homogenized and centrifuged for organelle preparation. The radioactivity of gossypol was measured in each subcellular fraction. The cell membrane fraction has the highest binding capacity for gossypol, and the majority of gossypol was located in the particulate fractions. Results of the present study provide information in understanding the regulatory mechanism of gossypol on antisteroidogenic and/or toxic effects in cultured bovine luteal cells. PMID- 1734163 TI - Chronopharmacological study of furosemide; (IX). Influence of continuous norepinephrine infusion. AB - Our previous studies have suggested that the adrenergic nervous system is involved in the mechanisms responsible for the time-dependent changes in the effects of furosemide in rats. To examine this hypothesis further, norepinephrine (150 micrograms/kg/hr) or its vehicle alone was infused subcutaneously by osmotic minipumps. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide were significantly greater at 12 am than at 12 pm in the vehicle infused group of rats. However these administration-time-dependent changes in the effects of furosemide and its urinary amount disappeared in the norepinephrine infused group of animals. Since chronic norepinephrine infusion is considered to disturb the axis of adrenergic nervous system, these data support the hypothesis concerning the mechanisms of this chronopharmacological phenomenon of furosemide. PMID- 1734164 TI - Legislative preview: an overview of legislative issues affecting Maryland medicine in 1992. PMID- 1734165 TI - Providers with HIV/AIDS--a new dilemma. AB - Recently, a great deal of attention has been focused on health care providers who have or may have the human immunodeficiency virus or, as it is known in its later stages, acquired immunodeficiency syndrome. This article explores some of the duties physicians have, or soon may have, to their patients and employers in the areas of testing, disclosure, and practice restraints. PMID- 1734166 TI - Diagnosis and management of asymptomatic primary hyperparathyroidism: a commentary. PMID- 1734167 TI - Imaging case of the month. Crohn's disease involving the terminal ileum. PMID- 1734168 TI - Are hypoglycemic reactions dangerous? PMID- 1734169 TI - A safe treatment for hyperemesis gravidarum? PMID- 1734170 TI - Current challenges in medical practice and research. PMID- 1734171 TI - Inhomogeneity correction for in vivo spectroscopy by high-resolution water referencing. AB - One of the most common sources of distortion in in vivo spectroscopy is the inhomogeneity of the main magnetic field. This effect is particularly problematic when performing spectroscopic imaging, as the shim cannot be simultaneously optimized for all voxels. In this paper we present a technique to measure inhomogeneity rapidly, then show how to use the measurement to improve the analysis of the spectrum. This technique can be applied in conjunction with any spectroscopic localization method and any spectral quantitation algorithm. We present results from spectroscopic imaging of phantoms, then show application to a single-voxel water-suppressed proton brain study. We find that the quantitation of the in vivo spectrum is made immune to inhomogeneous line broadening. PMID- 1734172 TI - Fast angiography using selective inversion recovery. AB - We have developed an enhancement of selective inversion recovery that allows us to obtain high-resolution angiograms in reduced scan time. By applying several read pulses following each tagging inversion pulse, we can obtain several phase encodes in each cardiac cycle, thereby reducing the total scan time required for a complete image. Using this technique, high-resolution angiograms can be obtained in as little as 15 s. Because the phase encodes are collected in short bursts separated by long pauses, care must be taken to maintain uniform signal weighting across phase-encoding views and avoid ghosting. We use an increasing flip-angle sequence to equalize signal level weighting across the readouts. The phase encodes are collected in a special order to minimize ghosting. A postprocessing technique is used to further reduce signal nonuniformity between phase encodes. This fast angiography technique can significantly reduce artifacts due to patient motion during scanning and is especially useful for imaging vasculature in regions of the body where respiratory motion is a problem. PMID- 1734173 TI - Spin-lattice relaxation in murine tumors after in vivo treatment with interferon alpha/beta or tumor necrosis factor alpha. AB - 1H NMR spin-lattice relaxation times (T1) were measured in vitro and in vivo in Friend leukemia cell tumors during subcutaneous tumor growth in syngeneic mice and after in vivo administration of either purified murine interferon alpha/beta (IFN) or recombinant tumor necrosis factor alpha (TNF). Untreated tumors exhibited monoexponential T1 relaxation independently of tumor age at least until Day 16 after implantation. Histological examinations showed that under these conditions tumors were highly homogeneous and substantially free of necrotic areas. Peritumoral administrations of either IFN or TNF did not significantly alter the tumor relaxation properties at early stages of inhibition of tumor growth. The longitudinal relaxation decay became instead clearly biexponential at later stages (more than 7 days of IFN treatment or 2 days after TNF administration). While the T1 relaxation behavior could be unequivocally correlated with the presence of necrotic areas in these tumors, it could not be considered as an early marker of the altered growth capability, induced by administration of either IFN or TNF. PMID- 1734174 TI - On the precision of diffusion/perfusion imaging by gradient sensitization. AB - Computer simulation is used to assess the precision and accuracy of diffusion and perfusion parameters derived from a set of gradient-sensitized images. Under ideal experimental conditions, a moderate signal-to-noise level (ca. 40) suffices to estimate diffusion coefficients to within 20% relative precision. However, estimation of a typical cerebral perfusion fraction of 5% to within 20% relative precision requires signal-to-noise levels of ca. 400. Simulations also show that systematic errors in perfusion fraction estimation, as well as underestimation of the uncertainties in perfusion parameters (by chi-squared analysis), will be found at moderate signal-to-noise levels. PMID- 1734175 TI - Contrast-to-noise ratios in maximum intensity projection images. AB - We present a statistical analysis of the maximum intensity projection (MIP) algorithm, which is commonly used for MR angiography (MRA). The analysis explains why MIP projection images display as much as a twofold increase in signal- and contrast-to-noise ratios over those of the source image set. This behavior is demonstrated with simulations and in phantom and MRA image sets. PMID- 1734176 TI - "One-shot" velocity microscopy: NMR imaging of motion using a single phase encoding step. AB - The use of the pulsed gradient spin-echo sequence in NMR microscopy enables the measurement of molecular translational motion and simultaneous construction of velocity and self-diffusion images, a technique that has been termed dynamic NMR microscopy. In this method the PGSE contrast gradient is stepped in a fourth dimension (q space) and so is inherently inefficient. Provided that one is prepared to sacrifice some of the additional information provided by the multiple PGSE gradient approach, it is possible to construct a velocity image alone by means of a single PGSE phase-encoding step. We illustrate applications of this method in which a signal from the stationary spins is nulled by the use of both gradient phase cycling and a final "z-storage" rf pulse. The limits to velocity resolution are around 10 microns s-1 in free water but can be considerably smaller for molecules with a low self-diffusion coefficient. We demonstrate this method in a study of water capillary flow at 12 microns transverse pixel resolution, extending the velocity range by employing a four-quadrant analysis method. This method is also used to measure vascular transport in a living plant and find a flow rate of around 45 microns s-1. PMID- 1734177 TI - Formulation of radiographically detectable gastrointestinal contrast agents for magnetic resonance imaging: effects of a barium sulfate additive on MR contrast agent effectiveness. AB - Complete and homogeneous distribution of gastrointestinal (GI) contrast media are important factors for their effective use in computed tomography as well as in magnetic resonance (MR) imaging. A radiographic method (using fluoroscopy or spot films) could be effective for monitoring intestinal filling with GI contrast agents for MR imaging (GICMR), but it would require the addition of a radiopaque agent to most GICMR. This study was conducted to determine the minimum amount of barium additive necessary to be radiographically visible and to evaluate whether this additive influences the signal characteristics of the GICMR. A variety of barium sulfate preparations (3-12% wt/vol) were tested in dogs to determine the minimum quantity needed to make the administered agent visible during fluoroscopy and on abdominal radiographs. Solutions of 10 different potential GI contrast agents (Gd-DTPA, ferric ammonium citrate, Mn-DPDP, chromium-EDTA, gadolinium oxalate, ferrite particles, water, mineral oil, lipid emulsion, and methylcellulose) were prepared without ("nondoped") and with ("doped") the barium sulfate additive. MR images of the solutions in tubes were obtained at 0.38 T using 10 different spin-echo pulse sequences. Region of interest (ROI) measurements of contrast agent signal intensity (SI) were made. In addition, for the paramagnetic contrast media, the longitudinal and transverse relaxivity (R1 and R2) were measured. A 6% wt/vol suspension of barium was the smallest concentration yielding adequate radiopacity in the GI tract. Except for gadolinium-oxalate, there was no statistically significant difference in SI for doped and non-doped solutions with most pulse sequences used. In addition, the doped and nondoped solutions yielded R1 and R2 values which were comparable. We conclude that barium sulfate 6% wt/vol added to MR contrast agents produces a suspension with sufficient radiodensity to be viewed radiographically, and it does not cause significant alteration in the MR signal appearance of most GICMR. These formulations can be useful for achieving optimal filling of the gastrointestinal tract prior to MRI. PMID- 1734178 TI - Diffusion imaging of the human brain in vivo using high-speed STEAM MRI. AB - This paper describes a new method for diffusion imaging of the human brain in vivo that is based on a combination of diffusion-encoding gradients with high speed STEAM MR imaging. The single-shot sequence 90 degrees-TE/2-90 degrees-TM (alpha-TE/2-STE)n generates n = 32-64 differently phase-encoded stimulated echoes STE yielding image acquisition times of 576 ms for a 48 x 128 data matrix. Diffusion encoding is performed during the first TE/2-interval as well as during each readout period. Phantom studies reveal a quantitative agreement of calculated diffusion coefficients with literature values. EKG triggering completely eliminates motion artifacts from diffusion-weighted single-shot STEAM images of human brain in vivo. While signal attenuation of the cerebrospinal fluid (CSF) is predominantly due to flow, that observed for gray and white matter results from diffusion. Evaluated diffusion coefficients yield (1.0 +/- 0.1) x 10(-5) cm2 s-1 for gray matter, (0.5 +/- 0.1) x 10(-5) cm2 s-1 for white matter with the diffusion encoding parallel to the main orientation of the myelin sheath of the neurofibrils, and (0.3 +/- 0.1) x 10(-5) cm2 s-1 for white matter and a perpendicular orientation. All studies were performed at 2.0 T using a conventional 10 mT m-1 gradient system. PMID- 1734179 TI - Reduction of susceptibility artifact in gradient-echo imaging. AB - A new technique with which susceptibility artifact in gradient-echo imaging can be reduced substantially by use of a tailored RF pulse is described. The proposed technique can ideally be applied to the case where high local magnetic field inhomogeneity is dominated by the susceptibility. The signal loss and void phenomena due to susceptibility in a voxel are studied and a correction method is also proposed. The description of the tailored RF pulse and its proposed application are given and experimental results obtained using a human volunteer with a 2.0-T KAIS NMR system are presented. PMID- 1734180 TI - Hypercarbia-induced changes in cerebral blood volume in the cat: a 1H MRI and intravascular contrast agent study. AB - Cerebral blood volume changes with arterial carbon dioxide were monitored by proton T1-weighted MR images following administration of the intravascular contrast agent Gd-DTPA labeled with human serum albumin. Without MR contrast, no significant image intensity changes were observed with PaCO2. Following contrast, regional brain image intensities increased significantly over control (0% inspired CO2) in cortical gray, white, and basal ganglia regions with increasing PaCO2 and returned to control intensities upon return to 0% inspired CO2. Imaging of through-plane and in-plane phantoms was performed to assess flow effects. Signal losses of 2 and 6% (relative to no flow) were observed for bulk velocities of 5 mm/s at TE values of 15 ms. An intravascular contrast agent may be useful for MRI monitoring of local cerebral blood volume changes during cerebral perturbations. PMID- 1734181 TI - In vivo 1H and 31P NMR spectroscopy of the developing rat brain. AB - The biochemical changes associated with brain maturation during the first 28 days postnatal were investigated utilizing proton and phosphorus-31 nuclear magnetic resonance spectroscopy in rat pups in vivo. Phosphocreatine was found to increase linearly during this period of development. Phosphomonoester was high at birth, peaked around the 10th day postnatal, and declined thereafter. N-Acetyl-aspartate was low at birth, increased in an approximately linear fashion, and reached adult levels by about Day 28 postnatal. Choline was high at birth and declined thereafter. Taurine, a sulfur amino acid abundant in fetal brain, was also present in high levels on the first day postnatal. PMID- 1734182 TI - Perfusion imaging. AB - Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies. PMID- 1734183 TI - In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil. AB - A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability. PMID- 1734184 TI - Multispectral analysis of uterine corpus tumors in magnetic resonance imaging. AB - The goal of this prospective study was to evaluate multispectral analysis techniques for automatic recognition of uterine cancer in magnetic resonance (MR) imaging. The first part of this study was an open training phase in which the statistical parameters of the various normal and pathological tissue types were estimated. This was followed by a test phase that was done as a blind experiment. Results from an extensive pathological examination of the surgically removed organs served as the reference for the diagnosis and various geometric measurements of the lesions. A radiological examination of the MR images was also performed. All malignant test tumors were correctly or close to correctly classified. However, parts of normal endometrium and other mucosal linings were also classified as adenocarcinomas. In addition, parts of some of the malignant tumors were classified as normal endometrium. The geometrical extension of the tumor and its relationship to the surroundings were slightly better predicted than those obtained by the radiologist. The results indicate that it is possible to differentiate and determine the local extension of some types of uterine malignancies based on the information present in MR images. PMID- 1734185 TI - NMR relaxation times in acute myocardial infarction: relative influence of changes in tissue water and fat content. AB - Tissue changes known to occur with acute myocardial infarction include increases in tissue water and lipid content. We sought to evaluate the relative contribution of alterations in tissue water and fat content to the changes of T1 and T2 relaxation times with infarction. Nine mongrel dogs underwent coronary artery occlusion for 6-12 h. T1 and T2 at 20 MHz and tissue water and fat content of normal and infarcted tissue were measured. Tissue water content, T1, and T2 were significantly greater in infarcted myocardium compared to normal (P less than 0.05). Tissue fat content, while not significantly different, increased linearly in infarcted samples as a function of duration of ischemia (r = 0.77). Despite this increase in fat content, only tissue water content was significantly linearly related to T1 (r = 0.97) and T2 (r = 0.91). Increases in T1 and T2 of infarcted tissue appeared to be most significantly influenced by changes in tissue water content. While total tissue fat content increased with duration of ischemia, it did not appear to significantly alter T1 or T2. PMID- 1734186 TI - Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma. AB - Surface coil MRI combined with spatially localized spectroscopy was used to noninvasively detect 1H signals from metabolites within an intracerebral malignant glioma in rats. The MRS pulse sequence was based upon two-dimensional ISIS, which restricted 1H signals to a column-shaped volume, combined with one dimensional spectroscopic imaging, which further resolved the signals into 8 or 16 slices along the major axis of the column. All experiments were executed with adiabatic pulses which induced uniform spin excitation despite the inhomogeneous radiofrequency field distribution produced by the surface coil transmitter. Surface coil MRI and MRS experiments were performed on phantom samples, normal rat brains, and rat brains harboring malignant gliomas. Spatially resolved in vivo 1H spectra of intracerebral gliomas revealed significantly decreased concentrations of N-acetyl-aspartate and creatine and increased lactic acid (or lipids) as compared to the contralateral hemisphere. These results demonstrate that metabolic abnormalities in intracerebral rat gliomas can be spatially resolved in a noninvasive manner using localized in vivo 1H MRS. PMID- 1734187 TI - General practitioner databases in Australia. AB - OBJECTIVE: General practitioner-based research has been hampered by the poorly defined database and the cost of continuous updating of lists of practitioners. Little is known about the general practitioner workforce. Fresh awareness by health planners of the serious maldistribution of general practitioners has heightened the need for workforce planning. Integral to this is the availability of an accurate listing of general practitioners. DATA SOURCES: A CD-ROM Medline review of all surveys involving general practitioners which were conducted in Australia in the period 1983-1990 was performed. All general practitioner listings still existing at the end of the decade were identified. STUDY SELECTION: Nine listings considered for use as general practitioner databases. DATA EXTRACTION: Each listing was assessed in six ways--quality of information provided, availability for research purposes, cost, potential to provide the correct postal address, ability to identify general practitioners in active practice and comparative advantage over other lists. DATA SYNTHESIS: Each listing has limitations and advantages, with individual peculiarities and variable information relating to identifying characteristics of general practitioners. None was specifically created for research or workforce planning purposes. The Medical Provider File (formerly called the Central Register of Medical Practitioners) was the most used list. CONCLUSIONS: We propose a framework for the ideal database and avenues for its development. PMID- 1734188 TI - Resistance to ciprofloxacin of respiratory pathogens in patients with cystic fibrosis. AB - OBJECTIVE: To determine the incidence of resistance to ciprofloxacin in respiratory pathogens isolated from patients with cystic fibrosis (CF) compared with that of isolates from patients without CF. The hypothesis was that repeated exposure of these respiratory pathogens to ciprofloxacin would reduce their sensitivity. DESIGN: Isolates of Pseudomonas aeruginosa and Staphylococcus aureus were obtained prospectively from sputa of patients with CF, as part of their routine care. The sensitivities of these isolates to ciprofloxacin were determined by standard agar dilution techniques. SETTING AND PATIENTS: The study was carried out in patients who attended the outpatient clinic or were treated as inpatients of a tertiary referral hospital. Sputa were obtained from 71 patients with CF (age range, 2-31 years) and isolates of P. aeruginosa and S. aureus were compared with those from 54 hospital patients who did not have CF. OUTCOME MEASURES: Sensitivities to ciprofloxacin, expressed as the minimal concentrations required to inhibit growth of the organisms (MIC), were used to make comparisons between different isolates and the same isolates within patients at different times. RESULTS: A higher incidence of ciprofloxacin resistance was displayed by isolates of P. aeruginosa from CF patients who had been previously prescribed ciprofloxacin (MIC50 of 2.0 mg/L and 4.0 mg/L for mucoid and non-mucoid strains respectively). The MIC of individual organisms tended to rise after a course of ciprofloxacin had been given to their host. A much lower incidence of resistance was displayed by isolates of P. aeruginosa from patients without CF (MIC50, 0.25 mg/L). Similarly, S. aureus isolates from patients with CF exhibited greater resistance to ciprofloxacin (MIC50, 32 mg/L) than isolates from other patients (MIC50, 0.75 mg/L). CONCLUSION: The resistance of P. aeruginosa appears to be related to ciprofloxacin exposure, so further development of resistance may be diminished by restricting the frequency of ciprofloxacin administration to individual patients. PMID- 1734190 TI - Recent developments in radiotherapy. PMID- 1734189 TI - Strongyloidiasis in North Queensland: re-emergence of a forgotten risk group? AB - OBJECTIVE: To describe the clinical presentation, diagnosis and management of strongyloidiasis in northern Queensland, and to identify predisposing factors for this infection. DESIGN: A five-year retrospective study of medical records of all cases diagnosed in a regional hospital microbiology laboratory, with follow-up by interview where possible. SETTING: The Townsville General Hospital. PATIENTS: A total of 14 cases of strongyloidiasis were identified, with patients ranging in age from 7 months to 59 years. RESULTS: Infected patients included nine Aborigines and two Vietnamese refugees, both high-risk groups. Of three Caucasians diagnosed, one was a war veteran, but the other two did not have significant travel histories; all three had lived or worked under insanitary conditions. In only one case was strongyloidiasis suspected; in most, it was diagnosed because of diarrhoea or blood eosinophilia which could not be related to the presenting illness. Thiabendazole treatment was effective in most cases. CONCLUSION: In northern Australia, strongyloidiasis can be acquired locally by Caucasians who live in unhygienic circumstances. It should be suspected in any person with unexplained abdominal pain, diarrhoea, cutaneous symptoms or blood eosinophilia, and the laboratory must be informed of the provisional diagnosis. PMID- 1734191 TI - Meta-analysis. Part 1: An assessment of its aims, validity and reliability. PMID- 1734192 TI - General practice financing: report of a "think tank". PMID- 1734193 TI - Sodium and blood pressure revisited. PMID- 1734194 TI - Drug and alcohol related health problems in primary care--what do GPs think? AB - OBJECTIVE: To examine knowledge, attitudes and beliefs of general practitioners (GPs) in the field of drug and alcohol related health problems. DESIGN: A cross sectional survey in which self-completion postal questionnaires were sent to all identifiable GPs in the Adelaide metropolitan area. Non-responders received a reminder letter and second questionnaire. SETTING, PARTICIPANTS: The target population was doctors whose principal activity was general practice, or who were in training for general practice. MAIN OUTCOME MEASURES: Demographic and "practice characteristic" information on participants. Measures of knowledge, attitudes and beliefs regarding alcohol consumption, smoking and over the counter medication. RESULTS: The response rate was 59.8%. More responders than non responders were affiliated with the Royal Australian College of General Practitioners. Alcohol consumption was perceived to be a more difficult issue than smoking to raise during consultations. GPs indicated that significant proportions of their patients were participating in hazardous drinking (mean estimate was 13.8% of patients), but only a third of respondents believed their effort in changing alcohol related behaviour would be effective. Sixty-one per cent of respondents identified hazardous daily levels of alcohol consumption for men consistent with National Health and Medical Research Council guidelines. In the case of women this figure was 42%. Longer reported appointment times were associated with greater reported levels of enquiry about alcohol consumption. CONCLUSIONS: New developments in medical training and systems of payment in general practice need to address both the pessimistic attitude of GPs in dealing with drug and alcohol related health problems, and apparent inconsistencies in defining hazardous alcohol consumption. PMID- 1734195 TI - The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand. AB - OBJECTIVE: To formulate recommendations for the role of corticosteroid therapy in the management of childhood asthma. DATA SOURCES: The recommendations are based on a review of the available literature and a variety of review articles on the efficacy and safety of corticosteroid therapy supplemented by personal experience in managing children with asthma. DATA SYNTHESIS: 1. Preventive therapy. Sodium cromoglycate should be considered first-line treatment. Inhaled corticosteroids are indicated in children who fail to achieve control on this therapy or those with severe disease. An initial dosage of 400-600 micrograms/day is recommended with subsequent variation in dosage related to clinical response. Large volume spacers can be used to improve aerosol delivery and minimise side effects. Indications for specialist assessment include: use of inhaled corticosteroids in children under 3 years of age; the requirement for high dose therapy (greater than 600 micrograms/day); or the need for regular oral corticosteroids. 2. Acute severe asthma. Systemic corticosteroid therapy is a valuable adjunct in the treatment of acute severe asthma and can be used safely in the short term. The efficacy of high dose inhaled corticosteroids in the management of acute severe asthma requires further evaluation. The need for systemic corticosteroid therapy signals the need for reassessment of that child's usual maintenance therapy. CONCLUSION: These recommendations are presented as a guide to the use of corticosteroid therapy in childhood asthma. In the individual child, the benefits of therapy need to be weighted against the possible risks, with the aim of maintaining good asthma control with the minimum dose of corticosteroid. PMID- 1734196 TI - Unexplained severe renal failure. PMID- 1734197 TI - The billion dollar question: can incontinence be reduced in nursing homes? PMID- 1734198 TI - Supply of organs for transplantation. PMID- 1734200 TI - Mammography is fallible. PMID- 1734199 TI - Illness associated with blue-green algae. PMID- 1734201 TI - Sodium valproate and oedema. PMID- 1734202 TI - Imipramine in primary nocturnal enuresis and the value of blood level measurements. PMID- 1734203 TI - Community acquired Flavobacterium meningosepticum pneumonia and septicaemia. PMID- 1734204 TI - Renal calculi and lithotripsy. PMID- 1734205 TI - Drug availability revisited: notification of clinical trials. PMID- 1734206 TI - Treatment of bipolar disorder. PMID- 1734207 TI - Smoking--another cause of palmar erythema? PMID- 1734208 TI - The physician as patient. PMID- 1734209 TI - The physician as parent of patient. PMID- 1734210 TI - Accuracy of mortality rates for livebirths 500-999 g birthweight. PMID- 1734211 TI - Paracetamol syrup induced diarrhoea. PMID- 1734212 TI - The first five years' clinical experience of the Australian National Liver Transplantation Unit. AB - OBJECTIVE: To report the first five years' clinical experience of the Australian National Liver Transplant Unit. PATIENTS: Three hundred and seventy patients were referred--292 adults (79%) and 78 children (21%). The major causes of liver failure in the adults were chronic active hepatitis (25%), primary biliary cirrhosis (12%), primary sclerosing cholangitis (12%), alcoholic cirrhosis (9%) and malignancy (9%). Ten per cent of patients were referred in fulminant hepatic failure. In children, the major causes were biliary atresia (40%) and inborn errors in metabolism (27%). RESULTS: Two hundred and sixty-three patients (71%) were accepted for transplantation. Of 158 (43%) accepted for early transplantation, 22 (14%) died before a donor became available. Four hundred and forty-three suitable organ donors were referred. One hundred and twenty-six patients, including 32 children (25%), received 137 grafts. Three patients with renal failure due to hyperoxaluria type 1 received concurrent renal grafts. Ninety-two patients survived (73%). For all recipients, one-year survival was 75%. Two, three and four-year survivals were 69%. One to four-year survivals for adults with benign conditions were 77%, contrasting with results for those with hepatic malignancy (40% one-year survival). Children weighing more than 8 kg had good outcomes whether they received whole grafts or reduced-size grafts (83% one to five-year survival in both cases). Infants weighing less than 8 kg who received reduced adult grafts did significantly worse (37% one to-five year survival, P less than 0.05). Thirteen (87%) of 15 patients with fulminant hepatic failure who received grafts survived. Five of these patients were given ABO incompatible grafts and two subsequently required retransplantation. All three patients with concurrent renal and hepatic grafts survived. Rehabilitation of survivors was excellent with 95% of adults and 100% of children pursuing normal activities. Only three grafts (2%) failed with primary non-function, all in infants because of graft infarction. Graft survival was significantly worse (P less than 0.01) in patients with a positive result to a direct cross match test against the donor. CONCLUSIONS: The need for liver transplantation in Australia is approximately eight per million of population per year. More donor offers are required to prevent deaths of patients on the waiting list. Reduced-size livers are successful for children and have alleviated considerably the critical shortage of paediatric donor livers. Successful treatment by liver transplantation can now be achieved in more than 80% of patients with non malignant liver disorders including those with fulminant hepatic failure not responding to conservative therapy. PMID- 1734213 TI - Survival in Hodgkin's disease by stage and age. AB - Patterns of care for Hodgkin's disease in the United States were surveyed through voluntary audits of hospitals with cancer programs nonapproved and approved by the Cancer Commission of the American College of Surgeons. Four hundred and seventy-three hospitals reported 6,345 patients diagnosed immediately preceding December 31, 1975. The survival rates varied with age, being better at younger ages and worse in the elderly. By pathologic stage, the younger patients faired better than the elderly in each stage grouping. Histologic type was not a factor in this poor prognosis. Hodgkin's disease in elderly patients has a different biologic behavior than in younger patients. PMID- 1734214 TI - Results of the LMT81 protocol, a modified LSA2L2 protocol with high dose methotrexate, on 84 children with non-B-cell (lymphoblastic) lymphoma. AB - From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA2L2 protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial tests (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 had CNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10 106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients. PMID- 1734215 TI - Soft-tissue sarcomas other than rhabdomyosarcoma in children. AB - Forty-seven children with nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) were treated by the Hematology-Oncology Service at Texas Children's Hospital, Houston, Texas, between 1958 and 1990. The male:female ratio was 1:1, and the median age was 11 years (3 weeks-16 years). A preexisting condition was found in 9/47 (19%) patients including neurofibromatosis (3), Down's syndrome (1), spina bifida (1), congenital facial asymmetry (1), giant pigmented nevus (1), juvenile onset diabetes mellitus (1), and acquired immune deficiency syndrome (1). The site of primary tumor was head and neck (3), trunk (33), and extremities (11). Twenty-four patients (51%) have survived free of disease with a median follow-up of 5 years (4 months-22 years). No patient whose disease recurred achieved a second remission. Of the 19 patients with group I disease, 16 (84%) survived free of disease. Wide excision of the primary tumor, with no microscopic residual disease, was associated with the greatest chance of disease-free survival. PMID- 1734216 TI - High-dose methylprednisolone sodium succinate as a single agent in relapsed childhood acute lymphoblastic leukaemia. AB - Twenty children received methylprednisolone (1 g/m2), daily for 5 to 8 days, as initial single agent therapy for relapsed acute lymphoblastic leukaemia. Bone marrow blasts were reduced to less than 5% in 2 and 5-10% in 3 of 12 patients with bone marrow relapses. In 3/9 with central nervous system relapses the cerebrospinal fluid (CSF) blasts completely cleared and were reduced in 4 others. In two patients with testicular relapses there was shrinkage of tumour and one patient with a navicular bone relapse became pain free. Toxicity was minimal. These results indicate high-dose methylprednisolone is an effective agent, particularly in the treatment of established central nervous system (CNS) disease and could contribute to early CNS directed therapy in acute lymphoblastic leukaemia. PMID- 1734217 TI - Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group. AB - An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses. PMID- 1734218 TI - Value of cytogenetics in the differential diagnosis of the small round cell tumors of childhood. AB - Small round cell tumors are among the most common problems in the differential diagnosis of cancer, even when more sophisticated histological techniques are utilized (Ezinger and Weiss: In Soft Tissue Tumors. St. Louis: CV Mosby, 1988, pp 668-683). Six cases of small round cell tumors are described the diagnosis of which was particularly difficult. Cytogenetic analysis provided useful information in all of them in making the definitive diagnosis. The reported cases stress the value of cytogenetic methods in approaching difficult diagnostic problems. PMID- 1734219 TI - Seizures and cortical dysfunction following high-dose cisplatin administration in children. AB - Four of eight children with advanced neuroblastoma treated with a rapid delivery high dose intensity cisplatin based regimen developed acute neurological toxicity. Three had seizures and one developed transient blindness. In the absence of other causes it seems probable that high dose cisplatin (200 mg/m2) as a continuous infusion over five days followed 10 days later by 80 mg/m2 infused over 48 hours was responsible. Other risk factors included an associated deterioration in renal function and neutropenia related fever. PMID- 1734220 TI - Neuroblastoma with intracranial involvement: an ENSG Study. AB - We report the experience of the European Neuroblastoma Study Group (ENSG) with central nervous system (CNS) involvement of neuroblastoma. Among this series of intensively treated patients, CNS neuroblastoma was diagnosed by computerised tomography (CT) scanning, rather than by autopsy. Cranial disease occurred in 5% of ENSG patients. Of 11 patients with intracranial disease, 4 had disease in the posterior fossa, a site rarely reported previously. Furthermore, 5 cases had CNS metastases at a time when there was no detectable disease elsewhere, rather than as part of extensive relapse. The pattern of disease we observed, at least for those with parenchymal disease, is in keeping with arterial spread. Although CT scanning is the optimal modality for identifying CNS disease, 2 cases had normal head CT scans prior to the onset of CNS disease. As most patients had symptoms of raised intracranial pressure (RICP) at the time the CNS disease was diagnosed, there does not seem to be any indication for routine CT scanning of the head at diagnosis, but this should be performed as soon as any symptoms or signs appear. With patients living longer with their disease, vigilance must be maintained during follow-up. PMID- 1734221 TI - Neuroblastoma diagnosed antenatally: a treatment dilemma with implications for screening. PMID- 1734222 TI - The unique association of malignant histiocytosis and a primary gonadal germ cell tumor. AB - Previous reports of the association between hematologic malignancies and germ cell tumors have been limited to patients with nonseminomatous tumors, exclusively of mediastinal origin. Among the various hematologic disorders, a large proportion have involved histiocytic tumors, either acute monocytic leukemia or malignant histiocytosis. We now report the first case of simultaneously occurring malignant histiocytosis and testicular embryonal carcinoma. The patient, an 18-year-old male, presented with hepatosplenomegaly due to malignant histiocytosis and was found on further evaluation to have a stage I testicular cancer consisting of teratocarcinoma with endodermal sinus elements. Despite aggressive chemotherapy, the patient died of malignant histiocytosis 6 months after the original diagnosis. The autopsy revealed widespread organ involvement with malignant histiocytosis and no evidence of residual germ cell tumor. This case demonstrates that germ cell tumors associated with hematologic malignancy do not arise solely in extragonadal sites. PMID- 1734223 TI - Isolated breast relapse after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia. AB - Unusual sites of relapses following bone marrow transplantation (BMT) for childhood acute lymphoblastic leukemia (ALL) are rarely reported. We report the case of a 16-year-old girl who presented with an isolated right breast relapse 8 months after allogeneic BMT for ALL in second remission. Biopsy showed an ALL infiltrate. Bone marrow and CSF were normal. The girl never showed before extramedullary involvement. She was treated with local radiotherapy and mild systemic chemotherapy. Nine months after breast relapse, she presented an isolated central nervous system relapse. The treatment of isolated extramedullary relapses following BMT is still controversial. PMID- 1734224 TI - Benign cystic mesothelioma of the peritoneum: the occurrence of an adult entity in a child. AB - Benign cystic mesothelioma of the peritoneum is considered a disease of adulthood occurring predominantly in women. We report a case of benign cystic mesothelioma of the peritoneum in an 11-year-old boy. The innumerable cystic lesions that varied in size occupied the entire peritoneal cavity. He underwent two laparotomies in a period of 15 months during which a partial removal of the tumor was performed. Four years after the second operation the child is well and active, despite significant tumor tissue left behind after the first two operations. The management of this disease is discussed, and the importance of a conservative approach minimizing the number of laparotomies and avoiding radical surgical intervention especially in childhood is emphasized. PMID- 1734225 TI - Decrease in childhood neuroblastoma death in Japan. Response to Dr. Cole et al. PMID- 1734226 TI - Cigarette smoking bans in county jails--Wisconsin, 1991. AB - In the United States, an increasing number of prisons and jails are adopting restrictions on cigarette smoking (1,2); these restrictions could affect approximately 10 million inmates (3). Although the importance of smoking restrictions in the workplace and some public places (e.g., health-care facilities, schools, and public transportation) has been well described (4), information about smoking restrictions in jails is limited. This report summarizes preliminary findings from a survey of sheriffs in Wisconsin to assess the development of policies and to characterize smoking restrictions among county jails in the state. PMID- 1734227 TI - Retrospective assessment of vaccination coverage among school-aged children- selected U.S. cities, 1991. AB - Preschool-aged children are at increased risk for vaccine-preventable diseases; outbreaks of these diseases in this age group occur predominantly among unvaccinated children (1). In the United States, vaccination rates of individual antigens required for children at the time they enter school are greater than 95%; however, vaccination rates for children at their second birthday are substantially lower (2) despite recommendations by the Immunization Practices Advisory Committee (ACIP) and the American Academy of Pediatrics that all children complete a schedule of vaccination by age 15-18 months.* To retrospectively assess vaccination levels among school-aged children at their second birthday, CDC, in collaboration with state and local health departments, is conducting surveys of vaccination levels among children entering school who reside in the 60 largest U.S. cities. This report presents findings from surveys completed in nine cities during 1991. PMID- 1734228 TI - Public health assessment--Russian Federation, 1992. AB - On December 25, 1991, the Russian Federation became an independent republic, and on January 2, 1992, restrictions on retail prices of most commodities were removed. From January 16 through February 6, a multidisciplinary team from the U.S. Food and Humanitarian Assistance Bureau (FHA) conducted an assessment of the needs for humanitarian and technical assistance, focusing on three regions in the southern Ural Mountains-Yekaterinburg, Perm, and Cheliabinsk-and three regions in south-central Siberia-Kusbas, Tomsk, and Novosibirsk. The FHA assessment included observations of health facilities, vaccine- and drug-storage centers, and disease control programs; review of health data at central, regional, and district epidemiology stations; and collection of food-price and income data through interviews with administrative authorities and surveys of markets and private homes. This report summarizes findings from the assessment. PMID- 1734229 TI - Physical fighting among high school students--United States, 1990. AB - During 1986, interpersonal violence caused an estimated 2.2 million injuries and more than 20,000 deaths in the United States. Physical fighting, a common form of interpersonal violence among adolescents, is a prominent cause of injuries and homicides in this age group. This article presents self-reported data about the prevalence and incidence of physical fighting among high school students in the United States during 1990. PMID- 1734230 TI - Street outreach for STD/HIV prevention--Colorado Springs, Colorado, 1987-1991. AB - Strategies to identify and influence persons at increased risk for infection with human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) require outreach to provide prevention messages directly to persons at risk, assist them to obtain prevention services, and encourage them to reduce risks. Street outreach programs complement CDC's information and education campaign "America Responds to AIDS" by providing persons with specific risk-reduction messages and materials. This report describes efforts to implement such approaches in Colorado Springs, Colorado, and presents preliminary results regarding the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections among female street prostitutes in that community. PMID- 1734231 TI - Lactic acidosis, ketoacidosis, and energy turnover: "figure" you made the correct diagnosis only when you have "counted" on it--quantitative analysis based on principles of metabolism. AB - Three cases are presented to illustrate that quantitative analysis based on physiologic principles can help resolve certain controversies in clinical medicine. For example, in case 1, a patient with severe hypoxia, the rate of production of lactic acid is so high that only restoration of delivery of oxygen is rational therapy. If the degree of hypoxia exceeds 5.6% of demand, dichloroacetate will not lessen the degree of acidosis. Further, even when delivery of oxygen is returned to normal, the rate of fall in lactate and rise in bicarbonate in plasma will be relatively slow. In case 2, a patient with diabetic ketoacidosis, our discussion stresses that the rate of production of ketoacids is not that rapid and that the degree of ketoacidosis is influenced to a major degree by decreasing the rate of oxidation of ketoacids in brain and kidneys. Case 3, a patient with severe hyperglycemia, illustrates that insulin will only promote the oxidation of glucose at a rapid rate once the levels of fatty acids and ketoacids decline to low levels. Accelerated transport of glucose by insulin is only a permissive action for the oxidation of glucose. PMID- 1734232 TI - Why kidneys fail. PMID- 1734233 TI - Environmental hazards and public health: lessons for the practice of medicine and for public policy. AB - The separation of occupational and environmental disease from the mainstream of medical practice has deep roots in the culture of the profession. Medical practice centered on individual patient care as nineteenth-century science yielded the therapeutic triumphs of the twentieth century. Social issues seemed remote to medical practitioners as the rewards of scientifically based therapies upstaged the unglamorous aspects of preventive medicine. Public health was left to politicians and bureaucrats. Victorian ambivalence toward the less successful members of society reinforced the isolation of medicine from public policy. As a consequence, physicians are largely ignored in contemporary debates about environmental hazards, to the detriment of both society and the profession. PMID- 1734234 TI - Diminished ratio of estrogen receptors to progesterone receptors in breast carcinomas of women who have had multiple miscarriages. AB - We examined the relationship of a history of miscarriage to the ratio of tumor estrogen receptors to progesterone receptors in 74 women with breast carcinoma evaluated between 1988 and 1990. Only women who had been pregnant and whose tumor contained both estrogen and progesterone receptors were included. Women with breast carcinoma and a history of two to four miscarriages had significantly lower ratios (less than 1) of tumor estrogen receptors to progesterone receptors than women with a history of zero or one miscarriage (greater than 1). This finding may be the result of a genetic anomaly in breast cancer patients that also affects the uterine environment during the reproductive years. PMID- 1734235 TI - The correlation between lupus anticoagulant and autoantibodies. AB - The presence of a positive lupus anticoagulant (LA) has recently been associated with reproductive failure. LA positivity and reproductive failure have also been associated with autoantibody abnormalities, especially antiphospholipid autoantibodies. Because the correlation between LA and autoantibody positivity has remained controversial, we retroactively investigated 326 sera of patients with reproductive failure for correlation between lupus anticoagulant and 15 autoantibodies separately for IgG, IgM, and IgA isotypes. LA by TTI and APTT correlated significantly (p less than 0.0001). Among 18 antiphospholipid isotypes, 6 (33%) correlated significantly with TTI, 5 (28%) with APTT, and 3 (17%) both with TTI and APTT. Among 15 isotypes to histone subfractions, 4 (27%) correlated significantly to TTI, 3 (20%) to APTT, and 2 (13%) to both LA assay methods. Of 12 isotypes to antipolynucleotide antibodies, 2 (17%) correlated significantly to TTI, 1 (8%) to APTT, and none to both assay methods. The correlation between LA and autoantibodies was less striking among LA-positive than LA-negative sera. LA by both TTI and APTT was primarily found to correlate with IgG and IgA autoantibodies. This occurs in decreasing frequency to phospholipids, histones, and polynucleotides. At abnormal levels of LA (by either method) the correlation with autoantibody levels is less pronounced and appears closer with IgM autoantibodies to histones and polynucleotides than antibodies to phospholipids. We conclude that the correlation between LA and autoantibodies, especially antiphospholipid antibodies, is less pronounced than often reported in the literature. Patients suspected to suffer from reproductive failure due to abnormal autoimmunity have to be screened not only with LA and/or selected antiphospholipid autoantibodies, but with a more comprehensive autoantibody profile. PMID- 1734236 TI - Intravenous fat emulsions and the pancreas: a review. AB - There is conflicting evidence of the effect of intravenous fat emulsions on pancreatic secretion. Intralipid is a safe component of intravenous nutritional support in patients with pancreatic fistulas, though it may minimally increase the volume, as well as the bicarbonate and amylase concentrations, of the output. Intravenous fat emulsions may rarely cause pancreatitis; this may be more likely in patients with Crohn's disease, given that three of the four reported cases occurred in patients with Crohn's disease. It is unclear whether hypertriglyceridemia secondary to the intravenous fat emulsion is a prerequisite for this complication to occur. Intravenous fat emulsions appear to be a safe component of intravenous nutritional support for the patient with pancreatitis, based on multiple studies proving their safety in a total of nearly 100 patients. It seems prudent to avoid hypertriglyceridemia secondary to intravenous fat emulsions, as this alone is a cause of pancreatitis, albeit uncommon, in patients with abnormalities of triglyceride metabolism. However, hypertriglyceridemia resulting from parenteral nutrition may be caused by glucose intolerance and not intravenous fat emulsion administration. PMID- 1734237 TI - Synthetic antiproteases in acute pancreatitis: an experimental study. AB - Acute pancreatitis was induced in 19 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Two groups, of six animals each, were treated with intravenous infusion of synthetic antiproteases: gabexate mesilate and nafamostat mesilate in doses of 1 mg/kg per hr. One group of seven animals remained untreated. Two untreated dogs died during the experiment. All the treated dogs survived. Hemodynamic data were monitored hourly during a 6-hr observation period. In the untreated animals, cardiac output, mean arterial pressure, and left ventricular stroke volume decreased rapidly; an increase of pulmonary vascular resistance and systemic vascular resistance was observed. Synthetic antiproteases, given as a therapy, improved the hemodynamic parameters significantly and prevented the animals from developing shock. Gabexate mesilate and nafamostat mesilate seem to be of value in the treatment of experimentally produced acute pancreatitis in dogs. PMID- 1734238 TI - Carcinoma of the gallbladder: review of the literature and report on 56 cases at the Beth Israel Medical Center. AB - Fifty-six patients with carcinoma of the gallbladder were treated at the Beth Israel Medical Center, New York City, during the 17-year period 1969-1987. The disease was most common among elderly women with cholelithiasis. Of the 56, 42 patients (75%) had liver metastases at operation; therefore, the majority underwent only exploratory laparotomy and biopsy. In 50 patients (89%), the tissue diagnosis was adenocarcinoma. Cholecystectomy was performed in 19 patients. Long-term survival occurred in patients with an incidental diagnosis of carcinoma of the gallbladder. The average survival in 44 patients for whom data were available, including long-term survivors, was 20 months. Of this group, 5 patients (11.3%) were still alive 5 years after diagnosis. Excluding those with an incidental diagnosis of gallbladder cancer, 1 patient (2.2%) survived longer than 5 years after diagnosis. Survival data in 3 of 4 patients who underwent extensive surgical treatment, such as liver wedge resection or hepatic lobectomy, averaged 23 months. Although no defined protocols were used, the addition of adjuvant chemotherapy or radiation therapy in patients treated surgically appeared to improve survival. Five patients survived more than 5 years after diagnosis, and 2 patients were alive after 17 years. PMID- 1734239 TI - An outbreak of bacteremic Campylobacter jejuni infection. AB - During September 1980, an outbreak of bacteremic Campylobacter jejuni infection occurred in metropolitan Los Angeles. The outbreak was recognized when blood cultures obtained from 11 previously healthy persons with acute febrile illnesses (characterized in over 80% by fever, diarrhea, and headaches) were positive for C. jejuni. All recovered after an illness that lasted a mean of 8 days. A surveillance system failed to reveal a concomitant outbreak of gastroenteritis. Isolates had identical biochemical characteristics, susceptibility patterns to antimicrobial agents, and serotypes. Isolates from 2 patients were found to be susceptible to bactericidal activity of normal human serum. When bacteremic case patients were matched with healthy controls, a significant association (p less than 0.05, odds ratio 10) between illness and consumption of processed turkey was established. Although turkey was not available for culture, and processing of turkey theoretically destroys Campylobacter, turkey carcasses are known to be heavily contaminated with the pathogen. PMID- 1734240 TI - Acute myocardial infarction in a long-term care institution for the aged. AB - We reviewed the clinical characteristics and outcome of cases of acute myocardial infarction occurring from January 1, 1985, through December 31, 1987, in the population of a long-term care institution for the elderly. The total number of patients in the series was 43. Comparisons were made between those patients transferred to a general acute-care hospital and those who remained at the facility. The most common initial symptoms of acute myocardial infarction in 32 of 48 patients were, in order, dyspnea, dizziness or syncope, precordial pain, and abdominal pain. Nine (of 43) patients were asymptomatic. In the 14 (of 43) patients transferred to an acute-care hospital, cardiac failure, arrhythmias, and cardiogenic shock were much more frequent than among those retained in the long term care facility. We concluded that a high index of suspicion for the diagnosis of acute myocardial infarction in the institutionalized elderly is indicated. Patients with mild infarction can be retained in long-term care institutions; resulting mortality from cardiac disorders should be low in adequately staffed and equipped long-term care institutions. PMID- 1734241 TI - HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis. AB - Epidemic increases in active syphilis have been reported in the geographic areas hit hard by acquired immunodeficiency syndrome. Although both epidemics have been associated with illicit substance abuse, the extent to which recent increases in syphilis are linked to the human immunodeficiency virus (HIV-1) epidemic is uncertain. In order to define the frequency of syphilis and HIV-1 coinfection in the pregnant patients seen at City Hospital Center at Elmhurst, we saved syphilis positive serologic specimens from obstetrical patients for anonymous HIV-1 antibody testing. Of 120 women who tested positive for syphilis, 7/120 (5.8%) had antibodies to HIV-1; of the 44 women with VDRL titers greater than or equal to 1:16 (suggestive of a recent infection), 1/44 (2.3%) had antibodies to HIV-1. PMID- 1734242 TI - Phycomycosis (mucormycosis) in differential diagnosis of cerebral mass lesions in intravenous drug users. PMID- 1734243 TI - Cortical blindness in postpartum preeclampsia progressing to eclampsia: case report. AB - A 23-year-old woman who had an uneventful prenatal course and normal delivery developed severe, generalized headache and blurred vision on postpartum day four. The patient was noted to have generalized hyperreflexia and sustained ankle clonus. The blood pressure was 170/100 mm Hg, there was no edema, and the urine showed trace proteinuria. The visual disturbance rapidly progressed to complete blindness with preserved pupillary reactions. The patient then had a generalized tonic-clonic seizure lasting about one minute. Treatment was initiated with intravenous diazepam and phenytoin, and there was no recurrence of seizure activity. Vision returned to normal and the patient made a complete recovery. This case is presented to demonstrate progressive postpartum pre-eclampsia and the importance of early recognition and treatment. Pathophysiologic mechanisms and treatment options are discussed. PMID- 1734244 TI - Duodenocolic fistula: an unusual presentation of esophageal squamous cell carcinoma. AB - Duodenocolic fistula, one of the less common forms of entero-enteric fistulas, is usually associated with colonic malignancies at the hepatic flexure or Crohn's disease of the colon or duodenum. We report an unusual case of duodenocolic fistula caused by metastatic esophageal squamous cell carcinoma in which the primary esophageal tumor remained asymptomatic. In several collected series of clinical and autopsy studies of over 2800 patients, no similar complication of metastatic esophageal squamous cell carcinoma has been reported. PMID- 1734245 TI - Hyperthyroidism in patients treated with lithium: report of nine cases. AB - Nine cases of hyperthyroidism which developed in patients on lithium therapy are presented and analyzed and the literature is briefly reviewed. The findings strongly suggest that lithium therapy does not cause hyperthyroidism. PMID- 1734246 TI - Ovarian pregnancy with ipsilateral mature cystic teratoma of the ovary: case report. AB - Ovarian pregnancy is a rare form of ectopic gestation. Mature cystic teratoma is the most common form of germ cell tumor, and usually occurs in the reproductive age group. The concomitant occurrence of an ovarian pregnancy with a mature cystic teratoma in the same ovary is exceedingly rare. We were able to find two other such cases in the literature. We present a case, and discuss the entity. PMID- 1734247 TI - A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. AB - BACKGROUND AND METHODS: The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. RESULTS: Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did not differ from that in the placebo group. In addition, the rate of new episodes of optic neuritis in either eye was higher in the group receiving oral prednisone, but not the group receiving intravenous methylprednisolone, than in the placebo group (relative risk for oral prednisone vs. placebo, 1.79; 95 percent confidence interval, 1.08 to 2.95). CONCLUSIONS: Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis. PMID- 1734248 TI - Biliary sludge as a cause of acute pancreatitis. AB - BACKGROUND: In about 20 to 40 percent of cases of acute pancreatitis, no cause can be found, and these are labeled idiopathic. In this study, we sought to determine the frequency with which patients with acute idiopathic pancreatitis have biliary sludge, a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules that is found predominantly in the gallbladder. METHODS: Between 1980 and 1988, we prospectively studied 86 patients who had acute pancreatitis. In patients with no known cause of pancreatitis and no ultrasonographic evidence of gallstones or dilatation of the biliary ducts, we determined how often biliary sludge was present and its subsequent fate by repeated microscopical examinations of bile samples and abdominal ultrasonography. The outcome of patients treated by cholecystectomy or papillotomy was compared with that of untreated patients. RESULTS: The pancreatitis was considered idiopathic in 31 of the 86 patients (36 percent), of whom 23 had microscopical evidence of biliary sludge. Biliary sludge was detected by ultrasonography in only 11 of the 23 patients (48 percent). The sludge detected by ultrasonography was composed of calcium bilirubinate granules in 10 and cholesterol monohydrate crystals in 1 (P = 0.003). Calcium bilirubinate granules were found more frequently in men (nine men vs. four women, P less than 0.001). Of the 21 patients in whom biliary sludge was the only finding (2 patients also had dilasted bile ducts when restudied), the 6 treated by cholecystectomy and the 4 treated by papillotomy had fewer recurrences of acute pancreatitis during follow-up (up to seven years) than the 11 untreated patients (P = 0.011). The presence of biliary sludge appeared to increase the likelihood of recurrent attacks of pancreatitis (P = 0.020). CONCLUSIONS: Biliary sludge is an underestimated cause of acute idiopathic pancreatitis. PMID- 1734249 TI - A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract. AB - BACKGROUND: Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival. METHODS: We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization. RESULTS: A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group. CONCLUSIONS: Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care. PMID- 1734250 TI - Osteopenia in men with a history of delayed puberty. AB - BACKGROUND AND METHODS: The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass. RESULTS: The mean (+/- SD) radial bone mineral density was significantly lower in the men with a history of delayed puberty than in the normal men (0.73 +/- 0.07 vs. 0.80 +/- 0.05 g per square centimeter; P less than 0.0002). Spinal bone mineral density was also significantly lower in the men with delayed puberty than in the normal men (1.03 +/- 0.10 vs. 1.13 +/- 0.11 g per square centimeter; P less than 0.003). Radial bone density was at least 1 SD below the mean value for the normal men in 15 of the 23 men with a history of delayed puberty, and spinal bone density was similarly decreased in 10 of the 23. CONCLUSIONS: Adult men with a history of constitutionally delayed puberty have decreased radial and spinal bone mineral density. These findings suggest that the timing of puberty is an important determinant of peak bone density in men. Because the peak bone mineral density achieved during young adulthood is a major determinant of bone density in later life, men in whom puberty was delayed may be at increased risk for osteoporotic fractures when they are older. PMID- 1734251 TI - The use of transcranial ultrasonography to predict stroke in sickle cell disease. AB - BACKGROUND: Stroke, especially cerebral infarction, is a major cause of morbidity and mortality in children with sickle cell disease. Primary prevention of stroke by transfusion therapy may be feasible if there is a way to identify the patients at greatest risk. Transcranial Doppler ultrasonography can measure flow velocity in the large intracranial arteries. The narrowing of these arteries, which leads to cerebral infarction, is characterized by an increased velocity of flow. METHODS: Using transcranial Doppler ultrasonography, we prospectively measured the velocity of cerebral blood flow in children and young adults being followed because of sickle cell disease. The results were classified as either normal or abnormal on the basis of the highest velocity of flow in the middle cerebral artery. Abnormal velocity was defined as a flow greater than or equal to 170 cm per second, a definition determined by post hoc analysis to maximize the predictive success of the test. The end point was a clinically apparent first cerebral infarction. RESULTS: Two hundred eighty-three transcranial ultrasound examinations were performed in 190 patients with sickle cell disease (age at entry, 3 to 18 years). After an average follow-up of 29 months, cerebral infarction was diagnosed in seven patients. In 23 patients the results of the ultrasound examinations were abnormal, and in 167 patients they were normal. The clinical and hematologic characteristics of the two groups were similar, but six of the seven strokes occurred among the 23 patients with abnormal ultrasound results (P less than 0.00001 by Fisher's exact test). In this group, the relative risk of stroke was 44 (95 percent confidence interval, 5.5 to 346). CONCLUSIONS: Transcranial ultrasonography can identify the children with sickle cell disease who are at highest risk for cerebral infarction. Periodic ultrasound examinations and the selective use of transfusion therapy could make the primary prevention of stroke an achievable goal. PMID- 1734252 TI - Androgen resistance--the clinical and molecular spectrum. PMID- 1734253 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 9-1992. Wide-complex tachycardia in a 65-year-old woman without previous evidence of cardiac disease. PMID- 1734254 TI - Corticosteroid treatment of acute optic neuritis. PMID- 1734255 TI - Acute pancreatitis--never leave a stone unturned. PMID- 1734256 TI - Sickle cell anemia, stroke, and transcranial Doppler studies. PMID- 1734257 TI - Systemic mastocytosis. PMID- 1734258 TI - Postnatal transmission of HIV infection. PMID- 1734259 TI - Postnatal transmission of HIV infection. PMID- 1734260 TI - Postnatal transmission of HIV infection. PMID- 1734261 TI - Psychological stress and the common cold. PMID- 1734262 TI - Emergency balloon valvuloplasty as initial treatment of patients with aortic stenosis and cardiogenic shock. PMID- 1734263 TI - Insulin resistance. PMID- 1734264 TI - Correction: platelet calcium metabolism in the prediction of preeclampsia. PMID- 1734265 TI - Herpes gladiatorum. PMID- 1734266 TI - Roche cuts controversial PCR fees, testing limits. PMID- 1734267 TI - Drug development. Orphan drug windfalls? PMID- 1734268 TI - Epidemiology. Leukaemia linked to radiation. PMID- 1734269 TI - EC biotechnology policy. Progress on animal patents. PMID- 1734270 TI - Genetic resources. A gene library that goes "moo". PMID- 1734271 TI - International collaboration. A lifeline from abroad. PMID- 1734272 TI - Research plans. Monopoly threatens variety. PMID- 1734273 TI - Biotechnology. Entrepreneurs look for customers. PMID- 1734274 TI - Universities. Democracy a mixed blessing. PMID- 1734275 TI - Gene expression. Dialogue with the cell cycle. PMID- 1734276 TI - Palaeoanthropology. A remote sense for fossils. PMID- 1734277 TI - Maintenance of MHC polymorphism. PMID- 1734278 TI - Language gap. PMID- 1734279 TI - Language gap. PMID- 1734280 TI - Molecular dissection of the secretory pathway. AB - A combination of biochemistry in animal cell-free systems and genetics in yeast is revealing the molecular machinery of the secretory pathway of eukaryotes. Transporting vesicles have a simple coat structure and employ a general mechanism for fusion that is conserved in evolution. PMID- 1734281 TI - Control of DNA synthesis genes in fission yeast by the cell-cycle gene cdc10+. AB - In the budding yeast Saccharomyces cerevisiae, cell-cycle control over DNA synthesis occurs partly through the coordinate expression in late G1 phase of many, if not all, of the genes required for DNA synthesis. A cis-acting hexamer element ACGCGT (an MluI restriction site) is responsible for coordinating transcriptional regulation of these genes at the G1/S phase boundary and we have identified a binding activity, DSC1, that recognizes these sequences in a cell cycle-dependent manner. In the distantly related fission yeast Schizosaccharomyces pombe, only one of the known DNA synthesis genes, cdc22+, which encodes a subunit of ribonucleotide reductase, is periodically expressed in late G1 (ref. 6). The promoter region of cdc22+ has two MluI sites and five related sequences, suggesting that similar controls over DNA synthesis genes could occur in fission yeast. We report here a binding activity in fission yeast that is very similar to DSC1 in budding yeast. We also show that the fission yeast cdc10+ gene product, which is required for Start and entry into S phase, is a component of this binding activity. PMID- 1734282 TI - A transcriptional hierarchy involved in mammalian cell-type specification. AB - Although transcriptional hierarchies have been extensively studied in invertebrates, their involvement in mammalian cell-type specification is poorly understood. Here we report a hepatocyte transcriptional cascade suggested by the expression patterns of hepatic transcription factors in dedifferentiated hepatomas and hepatocyte: fibroblast hybrids in which the liver phenotype was extinguished. These results indicated that the homeoprotein hepatocyte nuclear factor-1 alpha (HNF-1 alpha), and HNF-4, a member of the steroid hormone receptor superfamily, were regulated coordinately or in a hierarchy by a higher-order locus, independently of other hepatic transactivators. HNF-4 was implicated as an essential positive regulator of HNF-1 alpha, as deletion of an HNF-4 binding site in the HNF-1 alpha promoter abolished promoter activity, and HNF-4 potently transactivated the HNF-1 alpha promoter in cotransfection assays. Moreover, genetic complementation of dedifferentiated hepatomas with HNF-4 complementary DNA rescued expression of endogenous HNF-1 alpha messenger RNA and DNA-binding activity. Our studies therefore define an HNF-4----HNF-1 alpha (4----1 alpha) transcriptional hierarchy operative in differentiated hepatocytes but selectively inhibited by an extinguishing locus and somatic mutations which antagonize the liver phenotype. PMID- 1734283 TI - Characterization of cDNA for the large subunit of the transcription initiation factor TFIIF. AB - At least six chromatographically resolvable general transcription factors may participate in accurate initiation by RNA polymerase II in HeLa cell-derived systems. TFIIF (also termed FC, RAP30/74 and beta/gamma) can bind directly to RNA polymerase II in solution and decrease the affinity of RNA polymerase II for nonspecific DNA. From studies on the kinetics of transcription initiation, on the composition of transcription initiation complexes fractionated by acrylamide gel electrophoresis, and on template competition experiments, TFIIF is known to act at an intermediate stage in initiation complex formation. It acts after TFIID firmly associates with DNA, but coincidentally with or immediately after RNA polymerase II binding to DNA, and before the recruitment of factor TFIIE. TFIIF may or may not have DNA helicase activity. The small subunit (RAP30) of TFIIF has been cloned and shows some amino-acid sequence homology to bacterial sigma factors. We have partially sequenced the RAP74 protein from purified HeLa cells, cloned its complementary DNA and shown that its translation product can interact with RAP30 in vitro as well as in vivo. The cDNA predicts an amino-acid sequence that lacks obvious DNA or RNA helicase motifs. It has regions rich in charged amino acids, including segments containing a higher content of acidic amino acids than are found in strong transcriptional activators such as VP16. PMID- 1734284 TI - A cDNA encoding RAP74, a general initiation factor for transcription by RNA polymerase II. AB - RAP30/74 (also known as TFIIF, beta gamma and FC is one of several general factors required for initiation by RNA polymerase II. The small RAP30 subunit of RAP30/74 binds directly to polymerase and appears structurally and functionally homologous to bacterial sigma factors in their RNA polymerase-binding region. RAP30/74 or recombinant RAP30 suppresses nonspecific binding of RNA polymerase II to DNA and is required for RNA polymerase II to assemble stably into a preinitiation complex containing promoter DNA and the general factors TFIID, TFIIA and TFIIB; both RAP30 and RAP74 are physical components of the preinitiation complex. A complementary DNA encoding human RAP30 has been isolated, and here we report the isolation of a cDNA encoding human RAP74. RAP30 and RAP74 produced in Escherichia coli can be used in place of natural human RAP30/74 to direct accurate transcription initiation by RNA polymerase II in vitro. PMID- 1734285 TI - Type III restriction enzymes need two inversely oriented recognition sites for DNA cleavage. AB - Type III restriction/modification enzyme recognize short, non-palindromic sequences that can be methylated on only one strand, with the paradoxical consequence that during replication of what is in effect hemimethylated DNA totally unmodified sites arise. Why the unmodified sites are not subject to suicidal restriction was not clear. Here we show that restriction requires two unmodified recognition sites that can be separated by different distances but which must be in inverse orientation. All of the unmodified sites in newly replicated DNA are of course in the same orientation, which explains why they are not restricted. This result may be of relevance to other manifestations of anisotropy in double-stranded DNA, such as genetic imprinting. PMID- 1734286 TI - Novel NADPH-binding domain revealed by the crystal structure of aldose reductase. AB - Aldose reductase is the first enzyme in the polyol pathway and catalyses the NADPH-dependent reduction of D-glucose to D-sorbitol. Under normal physiological conditions aldose reductase participates in osmoregulation, but under hyperglycaemic conditions it contributes to the onset and development of severe complications in diabetes. Here we present the crystal structure of pig lens aldose reductase refined to an R-factor of 0.232 at 2.5-A resolution. It exhibits a single domain folded in an eight-stranded parallel alpha/beta barrel, similar to that in triose phosphate isomerase and a score of other enzymes. Hence, aldose reductase does not possess the expected canonical dinucleotide-binding domain. Crystallographic analysis of the binding of 2'-monophospho-adenosine-5' diphosphoribose, which competitively inhibits NADPH binding reveals that it binds into a cleft located at the C-terminal end of the strands of the alpha/beta barrel. This represents a new type of binding for nicotinamide adenine dinucleotide coenzymes. PMID- 1734287 TI - Assessment: magnetoencephalography (MEG). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 1734288 TI - Clinical and EEG features of status epilepticus in comatose patients. AB - We retrospectively evaluated the clinical and EEG features of status epilepticus (SE) in 47 comatose adult patients in whom SE was suspected clinically or because the EEG revealed repetitive electrographic seizures or continuous spike-and-wave activity. Three groups of patients were identified. Group-1 patients (n = 33) had SE both clinically and on EEG. They usually had subtle, clonic movements restricted to the eyes, face, and upper extremities, and the EEG most commonly showed repetitive electrographic seizures or continuous spike-and-wave activity. Group-2 patients (n = 9) also had subtle motor manifestations of seizures, but the EEG was not that of SE, consisting of either irregular slowing with frequent spikes and sharp waves, an irregular mixed-frequency background with episodic accentuation, or diffuse slowing; one patient also had an intermittent burst suppression pattern. The five patients in Group 3 lacked any clinical signs of seizures, but the EEG showed repetitive electrographic seizures or continuous spike-and-wave activity. There were no significant differences between groups in etiology of SE, response to therapy, or outcome, and there was no obvious relationship between the EEG findings and duration of SE. We conclude that recognition of SE in comatose patients may require both clinical and EEG evaluation since either approach by itself may fail to establish the diagnosis. Furthermore, the EEG findings in established SE do not necessarily progress through the series of defined stages suggested by some authors. PMID- 1734289 TI - 'De novo' absence status of late onset: report of 11 cases. AB - Absence status (AS) is a heterogenous epileptic syndrome that can occur at any age, usually in a context of prior epilepsy. Eleven cases of AS occurring in middle-aged patients who had no history of epilepsy were retrospectively collected over a 10-year period (10 women and one man; mean age, 58.6 years). Eight patients were receiving high doses of psychotropic drugs. Clinical and EEG presentation was similar to AS occurring in patients with prior epilepsy. Evaluation of precipitating factors revealed that AS coincided with benzodiazepine withdrawal in eight cases. Cofactors included excessive use of other psychotropic drugs, nonpsychotropic treatment, hypocalcemia, hyponatremia, and chronic alcoholism. CT demonstrated mild cerebral atrophy in six cases. There was no recurrence, even without chronic antiepileptic treatment. These data indicate that (1) most cases of "de novo" AS of middle age or late onset result from the addition of various epileptogenic factors; (2) AS can be considered a new and uncommon complication of benzodiazepine withdrawal, and (3) long-term administration of anticonvulsant medication may not be required. PMID- 1734290 TI - Prevention of stroke with ticlopidine: who benefits most? TASS Baseline and Angiographic Data Subgroup. AB - We examined the baseline characteristics of patients in the Ticlopidine Aspirin Stroke Study (TASS) to determine if the effects of the two treatments in preventing stroke differed in various subgroups. Patients with the following characteristics did less well on aspirin: elevated creatinine, hypertension or diabetes requiring treatment, or treatment with anticoagulant or antiplatelet drugs prior to their qualifying TIA or stroke. Women and patients with vertebrobasilar symptoms did particularly well on ticlopidine. We performed arteriography in 1,188 patients with carotid qualifying events. The frequency of stroke in patients with abnormal arteriograms ipsilateral to their symptoms was slightly higher than in those with normal carotid arteries. Ticlopidine was more effective in patients without carotid stenosis. Ticlopidine is more effective than aspirin in preventing strokes in patients having warning TIAs. The patients who benefit most from ticlopidine may be women, those who have vertebrobasilar symptoms, those with cerebral ischemic symptoms while on aspirin or anticoagulant therapy, and patients with diffuse atherosclerotic disease rather than high-grade carotid stenosis. PMID- 1734291 TI - Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. AB - We determined the prevalence of dementia and probable senile dementia of the Alzheimer type (SDAT) for biennial Exam 17 of the Framingham cohort (1982/1983). The prevalence of dementia was 30.5/1,000 for men and 48.2/1,000 for women and increased with advancing age. Cases of probable SDAT constituted 55.6% of all dementia cases. THe prevalence of SDAT was 11.7/1,000 for men and 30.1/1,000 for women and also increased with advancing age. Prevalence of dementia and probable SDAT were greater for women than men. The female:male ratio of prevalence for cohort members 75 years of age and older was 1.8 for all cases of dementia and 2.8 for cases of probable SDAT. PMID- 1734292 TI - Familial presenile dementia with psychosis associated with cortical neurofibrillary tangles and degeneration of the amygdala. AB - We report a family in which 13 members in three generations had the presenile (age 42 to 66 years) onset of dementia with an autosomal dominant pattern of inheritance. An early symptom in eight individuals was prominent antisocial psychotic or belligerent behavior, often leading to the initial clinical diagnosis of paranoid schizophrenia. Duration of illness was longer than is usual in Alzheimer's disease (AD), ranging from 14 to 26 years in six members. Three affected siblings and a cousin have come to autopsy, and all had neurofibrillary tangles without senile plaques in several regions of the neocortex, amygdala, and parahippocampal gyrus. The hippocampus was free of both neurofibrillary tangles and senile plaques in all four, but in three there was neuronal loss with gliosis in the CA1 region of Ammon's horn bilaterally. There also was neuronal loss and neurofibrillary tangles in the nucleus basalis. The neurofibrillary tangles were tau-2 and Alz-50 positive and were composed of paired helical filaments ultrastructurally. The disease in this kindred appears to be a unique hereditary disorder that is distinct from familial AD. PMID- 1734293 TI - Cardioskeletal mitochondrial myopathy associated with chronic magnesium deficiency. AB - A 3-year-old boy presenting with convulsions and carpopedal spasm had hypomagnesemia and hypermagnesuria due to congenital magnesium-losing nephropathy. Despite chronic oral and intermittent intravenous magnesium supplementation, he remained chronically hypomagnesemic. At age 4, he developed a progressive proximal myopathy and dilated hypertrophic cardiomyopathy that ultimately contributed to his death at age 14 years. Skeletal and cardiac muscle specimens showed a mitochondrial myopathy with increased numbers of enlarged, structurally abnormal mitochondria. Muscle magnesium content was markedly decreased. Chronic oral and intermittent intravenous magnesium supplementation may be inadequate to prevent the progressive cardioskeletal myopathy associated with the chronic magnesium deficiency of congenital magnesium-losing nephropathy. PMID- 1734294 TI - Symptomatic and asymptomatic high-grade carotid stenoses in Doppler color-flow imaging. AB - We examined 63 patients with 31 symptomatic and 44 asymptomatic carotid stenoses with Doppler color-flow imaging (DCFI); conventional Doppler duplex had shown a hemodynamic obstruction (greater than or equal to 80% stenosis) in all patients. Analysis of plaque surface morphology demonstrated more ulcerated plaques in symptomatic (43%) than asymptomatic (23%) stenoses. Although the frequency of homogeneous and heterogeneous plaques was not different, calcific lesions were more frequent in asymptomatic (46% versus 29%), and echolucent plaques, probably indicating mural thrombi, were more frequent in symptomatic (29% versus 11%) stenosis. Color-coded hemodynamic patterns, such as jet flow, poststenotic turbulence, or reversed flow, were not different in symptomatic and asymptomatic stenoses. Comparison of DCFI with 30 angiograms showed agreement in plaque surface analysis in 70%. DCFI measurements of area reduction in cross sections correlated with angiography in 85%, while DCFI tended to underestimate the degree of stenosis from diameter reduction in longitudinal cuts. The advanced DCFI technique identified distinct morphologic features but no hemodynamic patterns, separating symptomatic from asymptomatic high-grade carotid stenoses. PMID- 1734295 TI - A quantitative MRI study of vascular dementia. AB - We studied the MRI and clinical factors associated with dementia following stroke by quantifying ventricle-to-brain ratio (VBR), anatomic region of infarction, and cortical, subcortical, and white matter areas of infarction in 24 stroke patients with dementia and 29 nondemented stroke patients. The factors that most strongly correlated with dementia were total white matter lesion (WML) area, left WML, VBR, right WML, age, left cortical infarction area, left parietal infarction area, and total infarction area. Using discriminant analysis, these factors correctly classified 28 of 29 nondemented patients and 18 of 24 demented patients. Both cortical and white matter total infarction area measurements were strongly associated with dementia in stroke patients, suggesting that these factors strongly influenced the development of dementia following stroke. There was a strong association between dementia and left- but not right-hemisphere infarction area. The only demographic factor that strongly associated with dementia was age. PMID- 1734296 TI - Japanese crossed Wernicke's aphasia. AB - A right-handed Japanese man with no personal or family history of left-handedness developed severe Wernicke's aphasia, a mild constructional disorder, and slight left hemiparesis. MRI revealed infarction in the territory of the righ middle cerebral artery, including areas homologous to Broca's and Wernicke's areas. The cerebral blood flow in these areas remained diminished even after language activation. The most likely explanation is that language production occurred in the left Broca's area, while language comprehension occurred in the right Wernicke's area (a dissociated aphasia). PMID- 1734297 TI - 'Spectacular shrinking deficit': rapid recovery from a major hemispheric syndrome by migration of an embolus. AB - We studied the clinical features of a major hemispheric stroke syndrome with rapid recovery ("spectacular shrinking deficit" [SSD]) compared with stroke patients with the same major initial manifestations but without rapid recovery (non-SSD). There were 118 patients with an initial major hemispheric syndrome; 14 patients (12%) had SSD. All but one SSD patient met criteria for cardiogenic brain embolism. Angiographic examination within 24 hours after stroke onset demonstrated that the occlusion sites in SSD differed from those in non-SSD and suggested that rapid embolus migration had occurred in all SSD patients but in only five of 39 non-SSD. Infarcts in SSD were smaller and often scattered over the cortices and deeper structures. Hemorrhagic transformation was less frequent in SSD. In patients with a potential cardiac source of emboli, SSD was more likely to occur in nondiabetic men less than 60 years of age. PMID- 1734298 TI - Memory in a case of bilateral thalamic infarction. AB - The role of individual structures within the diencephalon for memory functioning is unknown. We present anatomic localization of lesions and a longitudinal neuropsychological profile of a young man who had a bilateral diencephalic stroke in the interpeduncular profundus arterial territory. MRI localized the lesions to the mamillothalamic tracts and inferior thalamic peduncle. The amnesia was characterized by severe impairment in explicit recall of new facts and events, while word-completion priming and remote memory were intact. We suggest that the memory deficit results from a disconnection of the diencephalon from the medial temporal region. PMID- 1734299 TI - Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum? AB - Postmortem examination of a 65-year-old anosmic woman revealed rudimentary olfactory bulbs, an imperforate cribriform plate, and sulcal abnormalities of the orbitofrontal surface of the brain. The remainder of the brain, skull, and body was normal. This abnormality most likely resulted from a local insult to the area of the cribriform plate during early fetal life, occurring after the induction of olfactory bulb differentiation, but before migration and complete differentiation of the olfactory bulbs. Such a lesion can be dated to approximately 11 to 12 weeks gestational age. The malformation may represent another variant in the arhinencephaly spectrum, but is termed "olfactory dysgenesis" or "olfactory hypoplasia" to separate it from true olfactory aplasia and arhinencephaly. PMID- 1734300 TI - MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease. AB - We evaluated a new magnetic resonance (MR)-based technique for performing volumetric measurements of temporal lobe structures. The technique was designed to assist in making the clinical diagnosis of dementia of the Alzheimer type (DAT). We chose specific anatomic regions of interest because of their known involvement in memory function and in the neuropathology of DAT and used a regression model to assess the effects of age on the volumes of the anterior temporal lobe (ATL) and the hippocampal formation (HF). These measurements were normalized by total intracranial volume (TIV). The volumetric measurements of both the normalized ATL and HF were significantly smaller (p less than 0.001) in DAT patients (N = 20) than in controls (N = 22), but the HF volumes provided much better separation between the two groups. Eighty-five percent of the DAT patients fell below the range of the HF/TIV measurement for the control subjects. This separation held up over the entire age range studied. Normalized volumes of both the HF and ATL decreased with age significantly for both the DAT patients and the controls. These results support the contention that MR-based HF volumetric measurements are accurate in differentiating DAT patients from cognitively normal elderly individuals. This technique may be a useful adjunct in making the clinical diagnosis of DAT. PMID- 1734301 TI - Contrast sensitivity is increased in a case of nonparkinsonian freezing gait. AB - We measured spatiotemporal contrast sensitivity and gait variables in a 60-year old man who had spontaneous episodes of freezing gait without any sign of rigidity or tremor. One major factor triggering freezing was the characteristics of visual space, as freezing episodes occurred during spontaneous walking and passing through apertures and never during walking with eyes closed. Initiation and maintenance of locomotion were greatly facilitated when transverse stripes with optimal intervals were placed on the ground in front of the patient. On the other hand, contrast sensitivity to low-to-intermediate spatiotemporal frequencies was increased in this patient when compared with that of elderly controls. These data suggest that hypersensitivity to visual stimulation and to modifications of the visual environment, associated with abnormal ocular motor behavior, can be one factor leading to the freezing gait phenomenon, which could be called "hypersensitivity braking" and be considered as a sensorimotor disorder. PMID- 1734302 TI - Two alien hand syndromes. AB - Review of the clinical characteristics and neuroanatomy of 20 reported cases of alien hand syndrome (AHS) and a patient of our own confirm that AHS is actually two distinct syndromes. Frontal AHS occurs in the dominant hand; is associated with reflexive grasping, groping, and compulsive manipulation of tools; and results from damage to the supplementary motor area, anterior cingulate gyrus, and medial prefrontal cortex of the dominant hemisphere and anterior corpus callosum. Callosal AHS is characterized primarily by intermanual conflict and requires only an anterior callosal lesion. the occurrence of frontal AHS in the dominant limb can be explained by an increased tendency for dominant limb exploratory reflexes coupled with release from an asymmetrically distributed, predominant nondominant-hemisphere inhibition. Callosal AHS is best explained by hemispheric disconnection manifested during behaviors requiring dominant hemisphere control. PMID- 1734303 TI - Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome). AB - We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins. PMID- 1734304 TI - [18F]-6-fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR-462). AB - PET studies were performed to investigate the effects of a new cathechol-O methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5 nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6 fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p less than 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 +/- 5.5% (mean +/- SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 +/- 5.0% (mean +/- SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD. PMID- 1734305 TI - Myotonic dystrophy: clinical assessment of muscular disability in an isolated population with presumed homogeneous mutation. AB - We evaluated the muscular disability of 295 patients affected by the adult form of myotonic dystrophy (DM) and living in the Saguenay-Lac-Saint-Jean region (Quebec, Canada). The patients are known to have a common ancestral couple, and a homogeneous DM mutation is presumed. Using a five-point muscular disability rating scale (MDRS), we confirmed, in each age group, the wide expressivity of the muscular involvement usually observed in DM. Based on the duration of the disease and the MDRS, we also found a great variation in the rate of disease progression. There were no significant relationships between the rate of disease progression and the sex of the patient, the sex of the affected parent, or the age at onset of the disease. Furthermore, there was an absence of association between the age at onset and the sex of the patient or the sex of the affected parent. The variable severity of the muscular involvement, and the absence of relationship between age at onset and rate of disease progression, suggest a multiallelic influence at the DM locus or at other loci. PMID- 1734306 TI - Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA. AB - We have studied five children with mitochondrial myopathy manifesting within or soon after the first year of life. Muscle biopsies showed ragged-red fibers and decreased respiratory chain activity. All five patients had a severe decrease (2 to 34% of normal) in the amount of muscle mitochondrial DNA (mtDNA). The depletion of mtDNA correlated with absence of mtDNA-encoded translation products and with loss of cytochrome c oxidase enzyme activity in individual muscle fibers. This mitochondrial myopathy of childhood illustrates one phenotypic expression of a novel pathogenetic mechanism in mitochondrial diseases, the specific depletion of mtDNA in affected tissues. PMID- 1734307 TI - Muscle acetylcholine receptors complexed with autologous IgG reflect seropositivity but not necessarily in vivo binding. AB - The diagnosis of acquired myasthenia gravis (MG) in apparently seronegative individuals is aided by finding immunoglobulin complexed to acetylcholine receptors (AChR) and a reduction in the number of binding sites for alpha bungarotoxin (alpha-BTx) in nerve-muscle biopsies. In this study, we found that anti-AChR antibodies in extracellular fluids can complex with cytoplasmic epitopes of AChR in the process of muscle extraction. When normal muscle was briefly exposed to antibodies (greater than or equal to 0.3 nmol/l) in the initial step of tissue homogenization (before detergent extraction), membranous AChR became complexed with IgG. This was so even with a nonmyasthenogenic monoclonal antibody specific for the alpha-subunit's presumptive cytoplasmic segment 366-389. We also found that antibodies reactive with AChR's alpha-BTx binding region can significantly lower apparent yields of alpha-BTx binding sites extracted from muscle. Thus, the finding of IgG complexed to AChR extracted from biopsied muscle does not necessarily reflect in vivo binding but, nevertheless, is a sensitive indicator of AChR seropositivity in patients suspected to have MG. PMID- 1734308 TI - Advanced cerebrovascular disease and the death of Vladimir Ilyich Lenin. PMID- 1734309 TI - The changing 19th-century view of epilepsy as reflected in the West Riding Lunatic Asylum Medical Reports, 1871-1876, vols 1-6. AB - The West Riding Lunatic Asylum Medical Reports (WRLAMR) were published from 1871 to 1876. Organized by Sir James Crichton-Browne at a little-known mental asylum in northern England, the WRLAMR contains many historically important works in neurology by such landmark figures as Sir David Ferrier and John Hughlings Jackson. The writings on epilepsy in the WRLAMR are particularly important and reveal the 19th-century shift in understanding the etiology of seizures. PMID- 1734310 TI - Endothelins and the nervous system. PMID- 1734311 TI - Contralateral disappearance of parkinsonian signs after subthalamic hematoma. AB - A man with Parkinson's disease (PD) suddenly developed a left hemiballismus, and the CT showed a hematoma of the right subthalamic nucleus. After the ballistic movements had disappeared, akinesia and the other parkinsonian signs did not reappear on the left. This clinical case confirms the involvement of the subthalamic nucleus in the akinesia of PD, as suggested by recent experimental data. PMID- 1734312 TI - Cerebral infarction complicating intravenous immunoglobulin therapy for polyneuritis cranialis. PMID- 1734313 TI - Propranolol therapy for shuddering attacks. PMID- 1734314 TI - Ocular tilt reaction following lateral pontomedullary infarction. PMID- 1734315 TI - Short-term memory impairment in an alert patient as a presentation of herpes simplex encephalitis. PMID- 1734316 TI - Acute and persistent parkinsonism after use of diquat. PMID- 1734317 TI - Nonconvulsive status epilepticus following electroconvulsive therapy. PMID- 1734318 TI - HIV nomenclature. PMID- 1734319 TI - Pupils in neurosyphilis. PMID- 1734320 TI - Toluene and visual loss. PMID- 1734321 TI - PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients. AB - We used the polymerase chain reaction (PCR), a method useful in the detection of Borrelia burgdorferi in vitro, to evaluate CSF in patients thought to have neuroborreliosis. Nested pairs of oligonucleotide primers were designed to recognize the C-terminal region of B burgdorferi OspA. CSF samples were obtained from (1) patients with immunologic evidence of systemic B burgdorferi infection and clinical manifestations suggestive of CNS dysfunction, (2) seronegative patients with clinical disorders consistent with Lyme borreliosis, and (3) patient and contamination controls; all were analyzed in a blinded fashion. PCR detected B burgdorferi OspA DNA in CSF of (1) 10 of 11 patients with Lyme encephalopathy, (2) 28 of 37 patients with inflammatory CNS disease, (3) seven of seven seronegative patients with Lyme-compatible disorders, and (4) zero of 23 patient controls. Zero of 83 additional contamination controls were PCR-positive. In eight patients from whom we obtained CSF before and after parenteral antimicrobial therapy, PCR results invariably predicted clinical outcome accurately. PMID- 1734322 TI - Surgical treatment of cervical spondylotic myelopathy: time for a controlled trial. AB - Surgical procedures on the cervical spine are accepted therapies for the myelopathy of cervical spondylosis. However, reported improvement rates vary widely, and many reports indicate improvement in about one-half of the cases. It has not been proven that outcome after surgery is better than the natural history or conservative therapy. Radiographic or imaging evidence of cord impingement or compression may be seen in asymptomatic people. There are no clear guides to the selection of patients who may benefit from the operation and there has been no standardization of preoperative evaluation, trials of conservative therapy, ascertainment of progressive disability, or assessment of outcome. A multicenter controlled trial might answer these questions. PMID- 1734323 TI - Cardiac rhythm during temporal lobe seizures. AB - We studied the neuroanatomic correlates of ictal tachycardia in 27 seizures from five patients with unilateral temporal lobe epilepsy being evaluated with bilateral temporal lobe depth electrodes and orbitofrontal subdural electrodes. There were 11 complex partial seizures, three simple partial seizures, and 13 subclinical seizures. For all seizures, heart rate (HR) increased in a graded fashion as new cortical regions anywhere in the brain were recruited into the seizure. HR plateaued at the new level despite EEG frequency changes until the next region became involved. Increases in HR did not correlate with increased duration of seizures but rather with volume of brain involved. Restricted amygdaloid seizure activity was generally insufficient to alter HR. We conclude that the amygdala has a limited role in modulating HR during seizures, and ictal tachycardia depends principally on the volume of cerebral structures recruited into a seizure. PMID- 1734325 TI - Serial gadolinium-enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. AB - In the planning of MRI protocols to monitor disease activity in multiple sclerosis (MS), the clinical subtype needs to be considered. In this serial gadolinium-enhanced MRI study, we demonstrated differences between patients with early relapsing/remitting MS and benign MS in both the production of new lesions and the occurrence of enhancement. PMID- 1734324 TI - Shunting normal-pressure hydrocephalus: do the benefits outweigh the risks? A multicenter study and literature review. AB - We performed a multicenter retrospective study in 166 consecutive patients shunted for presumed normal-pressure hydrocephalus (NPH) in the four neurosurgical departments of Amsterdam. Overall improvement occurred in 36%, substantial improvement in 21%. In the subgroup of idiopathic NPH (N = 127), marked improvement was only 15%. The incidence of shunt-responsive NPH in our area was 2.2/million/year. The rate of severe and moderate shunt-related complications was 28%, leading to death or severe residual morbidity in 7%. The substantial benefit/serious harm ration in the whole group was only three (21%/7%), decreasing to 1.7 in idiopathic NPH. By excluding patients at high surgical risk, this ratio might have risen to 10 in the whole group and to six in idiopathic NPH. Our experience is much less favorable than that encountered in the literature, reporting overall improvement in 74% and marked improvement in 55% of the shunted patients. We conclude that NPH is probably a very rare and still overdiagnosed syndrome and that the overall morbidity rate for each patient demonstrating meaningful improvement is high. PMID- 1734326 TI - Symptomatic retrochiasmal lesions in multiple sclerosis: clinical features, visual evoked potentials, and magnetic resonance imaging. AB - We have studied 18 patients with relapsing-remitting multiple sclerosis (MS) who had symptomatic visual field defects due to retrochiasmal lesions. In 17, the lesion responsible was identified by magnetic resonance imaging (MRI), computed x ray tomography (CT), or both. The lesion responsible involved the posterior optic radiations in eight cases, the optic tract and lateral geniculate nucleus in six, and the posterior limb of the internal capsule in three. The prognosis for recovery of the field defect was good; complete recovery occurred in 14 patients, and only two showed no recovery at all. The striking characteristic of the lesions was that most were unusually large; indeed, many were detectable on CT as well as MRI. Half-field asymmetries of either amplitude or latency of the visual evoked potentials (VEPs), consistent with a postchiasmal lesion, were present in only five out of 13 patients acutely. In only three of these did the abnormality persist at follow-up. We conclude that only large postchiasmal lesions are likely to cause symptomatic homonymous field defects in MS, usually characterized by rapid recovery. Hemifield VEPs have a low sensitivity for the detection of postchiasmal as compared with prechiasmal abnormalities. PMID- 1734327 TI - Frequent involvement of the optic radiation in patients with acute isolated optic neuritis. AB - Magnetic resonance imaging revealed asymptomatic lesions in white matter regions corresponding with the optic radiations in 20 of 28 patients (71%) with clinically isolated optic neuritis. In contrast to the findings with symptomatic lesions, there was no relationship between the latency of the visual evoked potential and the presence of these asymptomatic posterior visual pathway lesions. PMID- 1734328 TI - Brain MRI and electrophysiologic abnormalities in preclinical and clinical adrenomyeloneuropathy. AB - We describe the neurophysiologic abnormalities in 17 patients with clinical adrenomyeloneuropathy (AMN), an adult phenotype of X-linked adrenoleukodystrophy (ALD). These abnormalities also allowed the early recognition of the AMN phenotype in three asymptomatic boys with biochemically proven ALD. In 14/16 adult AMN patients, there were cerebral white matter abnormalities on MRI which were severe and comparable with cerebral ALD in four of the patients. PMID- 1734329 TI - Decreased cerebral glucose utilization in myotonic dystrophy. AB - To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease. PMID- 1734330 TI - Psychogenic seizures: ictal characteristics and diagnostic pitfalls. AB - We analyzed ictal features of psychogenic seizures using video-EEG recordings in 47 patients and reviewed the medical records to determine if patients received antiepileptic drug therapy and whether they were treated pharmacologically for status epilepticus. Unresponsive behavior in the absence of motor manifestations was the single most common ictal presentation. Motor characteristics previously considered to distinguish psychogenic seizures (out-of-phase limb movements, side to-side head movements, pelvic thrusting) were infrequent. Most patients (74%) received anticonvulsants, and six were treated as status epilepticus. Slow, subtle writhing or in-phase limb movements were most likely to be mistaken for status epilepticus. Physicians, assuming that the spells constituted a neurologic emergency, omitted the neurologic examination and chart review and proceeded with aggressive pharmacotherapy based merely on observation. PMID- 1734331 TI - Fetal drug therapy: an overview of selected conditions. AB - Fetal drug therapy may be defined as the administration of any drug for the primary or sole purpose of treating a fetal disorder or in the hope of improving the capacity for later intrauterine or postnatal adaptation. In several intrauterine conditions, the drug exposure has been directed at the fetus rather than the mother. Progress in clinical investigation has been slowed by often unfounded fears of malformations and potential litigation. Since 1975, federal regulations have required that the fetus be protected and subjected to no more than minimal additional risk. Although no large-scale trials have been reported, drug administration has been proven to aid the fetus in many circumstances. Such treatment has been administered primarily during the second or third trimester and is generally short-term, preventive, and without apparent risk to the consenting mother. The published reports have made obstetricians aware of both the limits of our knowledge in this area and new applications for innovative fetal monitoring by the latest technology. Whether such therapy has a role in the care of the unborn infant will depend on accumulation of a larger body of information and the continued cooperation of basic scientists and clinical investigators. PMID- 1734332 TI - Exercise in pregnancy. PMID- 1734333 TI - Estrogen and bone metabolism. PMID- 1734334 TI - [Liver specific gene expressions in human fetal hepatocyte culture]. AB - The authors studied the function of human fetal liver cell--on level of DNA and gene regulation--by methods of molecular biology. Experiments were done under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee. They conclude that human fetal liver culture may serve as a suitable in vitro modell for study of the liver specific gene expressions. They found that cultured human fetal liver cells from second trimester express albumin and AFP. They demonstrate that fetal hepatocytes--like adult hepatocytes- respond to the inflammatory mediators, IL-1, IL-6 and TNF, by induction of CRP and alpha-1-Ach expression and regression of albumin synthesis proving the ability of fetal hepatocytes to produce an acute phase response. PMID- 1734335 TI - [Five-year follow-up pulmonary function studies in patients with anti-trypsin deficient pulmonary emphysema]. AB - Five-year follow-up study was carried out in pulmonary emphysematous patients with intermediate antitrypsin deficiency. The examinations showed no deterioration in the clinical state of the patients but in some parts of the controlled functional parameters a statistically significant worsening was found in this period of study. PMID- 1734336 TI - [The role of imitation in suicidal behavior]. AB - The authors analyse the modelling effect of the suicide of the first Hungarian beauty queen. After the publication of a book, a film and the newspapers about her suicide increased significantly the number of suicides committed by young females by the same method (Lidocain pill). During this period the consumption of Lidocain pills decreased in Hungary. The monthly and seasonal fluctuation of suicides committed by other methods is different from these changes. The suicide of celebrities mediated by the mass media can become modell through identification for a people in crisis situation. PMID- 1734337 TI - [Connection between microalbuminuria and subclinical cardiovascular autonomic neuropathy in diabetic children]. AB - Cardiovascular tests were investigated in 16 microalbuminuric, in 20 normoalbuminuric diabetic children and a control group of 20 healthy children. Comparing to the control group, in both of two diabetic groups a similar increase in resting heart rate (74.5 +/- 2.5/min vs. 87.8 +/- 3.5/min, p less than 0.01, and 83.6 +/- 3.2/min, p less than 0.05) and a decrease in hyperventilatory arrhythmia (32.3 +/- 1.2/min vs. 20.1 +/- 0.8/min, p less than 0.01, and 17.2 +/- 0.8/min, p less than 0.01) was observed. In the diabetic group with microalbuminuria in comparison with both the control group and the normoalbuminuric group there was a lower standing/lying heart rate ratio (1.02 +/ 0.03 vs. 1.30 +/- 0.05, p less than 0.01, and 1.22 +/- 0.05, p less than 0.05), a pronounced orthostatic decrease in blood pressure (15.1 +/- 0.3 mmHg vs. 2.0 +/ 0.1 mmHg, p less than 0.001, and 5.0 +/- 0.2 mmHg, p less than 0.01) and a diminished increase in blood pressure during sustained handgrip (6.3 +/- 0.2 mmHg vs. 14.0 +/- 0.3 mmHg, p less than 0.01, and 12.2 +/- 0.3 mmHg, p less than 0.05). The occurrence of cases with distinct autonomic dysfunction (3 or more abnormal cardiovascular tests) proved to be more frequent in the group with microalbuminuria than in the diabetic group with normal albumin excretion (6/16 vs. 1/20, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734338 TI - [Delayed diagnosis of infectious endocarditis]. AB - Three cases are presented to show examples of mistakes in the diagnosis and treatment of infective endocarditis which led to serious complications. The role of echocardiography in the early diagnosis and in the recognition of complications, the importance of bacteriologic diagnosis in the choice of antibiotic treatment and the need of timely surgical treatment are emphasized. PMID- 1734339 TI - [Carcinoid tumor of the breast]. AB - Two cases of carcinoid breast tumour are presented by the authors. Discussing the diagnostic and therapeutic possibilities, it is emphasized that this type of tumour represent a bad prognosis, in spite of the relative benign behaviour of the carcinoid tumour of other organs. In case of carcinoid tumour of the breast, radical operation and careful follow-up is recommended. PMID- 1734340 TI - [A new method for the termination of cervical pregnancy]. AB - The authors described a 7 weeks old cervical pregnant case, whome was administered 250 mg methotrexate in infusion to eliminate the throphoblastic tissue. 3 days later the HCG was negative in the urine. After the dilatation of cervix by laminaria, the collapsed amniotic sac came from the cervix with minimal hemorrhage. They suggest the method is suitable to prevent the serious complications of cervical pregnancy. PMID- 1734341 TI - [The role of different committees and individuals in the ethical position on the new methods of human reproduction]. AB - Due to the research on assisted human reproduction and the application of its results we face new type ethical dilemma which had never existed before. The traditional system of ethical values does not provide a safe basis for judgement of our actions. One of the challenging questions is who has the right to authorize or prohibit performing different procedures. There might be necessary and justifiable taking into account the opinions of various bodies (professional committees, national and institutional ethical committees, religious bodies, parliamentary representatives and private organizations or persons). The authors introduce the activities of the role and importance of these bodies and investigate the position of the research and clinical professionals in obtaining permission for the application of ethically sound or less criticizable procedures. The importance of the provision of continuous and many-sided information for wide range of the society is underlined. PMID- 1734342 TI - [Experience with the surgical management of constrictive pericarditis]. AB - 61 patients were operated on for constrictive pericarditis at the Cardiovascular Surgical Clinic of Semmelweis Medical University in the last 33 years. The average hospital mortality of the surgical pericardiectomy was 4.9%. The final conclusions of this retrospective and follow up study are as follows: pericardiectomy is the method of choice in the treatment of constrictive pericarditis, since it does not has any therapeutic alternative, its hospital mortality is low and it results excellent early and late postoperative functional effects. PMID- 1734343 TI - [Cases of familial leukemia-lymphoma in Szabolcs-Szatmar-Bereg County]. AB - Nine cases of familial malignant haematologic diseases were found by authors. Demonstrating the clinical pictures and the developments of nine pairs of cases (Hodgkin's disease--non-Hodgkin's lymphoma, Hodgkin's disease--chronic lymphocytic leukaemia, non-Hodgkin's lymphoma--acute lymphoblastic leukaemia, hairy cell leukaemia--acute lymphoblastic leukaemia, chronic lymphocytic leukaemia--acute myelogenous leukaemia, non-Hodgkin's lymphoma--chronic lymphocytic leukaemia, and three times chronic lymphocytic leukaemia--chronic lymphocytic leukaemia) authors want to give data about occurrences of familial leukaemia/lymphoma in their county. PMID- 1734345 TI - [Differential diagnosis in patients with fever at the department for infectious diseases of a county hospital]. AB - Between the 1st of January 1985 and the 31st of december 1989 101 patients were admitted for fever. Their data were analysed retrospectively. The patients were divided into three groups according to the diagnostic procedures. 32 patients belonged to the first group. The causes of their fever were diagnosed within 24 hours by simple clinical and laboratory means. The second group held 42 patients whose diagnosis were made within one week after detailed laboratory and clinical examinations. The third group (21 patients) fulfilled the criteria of FUO (Fever of Unknown Origin), and the authors analyse this group of patients. Most of the FUO group, 11 patients were diagnosed as infectious origin, 1 tumor, 4 autoimmune. In three cases the diagnosis remained unknown. Authors conclude that patients coming to hospital with fever should deserve more attention of specialist infectologists. PMID- 1734344 TI - [Relationship between congenital heart disease and various factors affecting pregnancy]. AB - In a prospective epidemiological study data of 24,732 pregnancies were analysed by computer programmes for the incidence of congenital heart disease (CHD) and its relationship to various factors affecting pregnancy (age and weight of mother, smoking, alcohol-, and coffee-consumption, usage of oral contraception). Frequency of CHD was 0.9%. Data showed that CHD could be associated with alcohol consumption, smoking, maternal age. Other factors like coffee consumption or taking oral contraceptive tablets did not influence the frequency of CHD. Authors conclude that in the prevention of CHD, reduction or even omission of both alcohol consumption and smoking are highly justified. PMID- 1734347 TI - [Trace element deficiency in healthy subjects?]. PMID- 1734346 TI - [Alkaptonuria-ochronosis]. AB - The authors describe the case of a 40-year old female patient. Since her childhood she realised of her urine the black discoloration of the underwear. For about a year, without subjective complaints, blue-black color of the skin involved the axillae and pinnae. For a year appeared the increased pain of thoracal and lumbal spine column and the limitation of motion of these parts. The examination of urine, histological and electron microscopical findings, the X-ray photograph of the spinal column confirmed the diagnosis of alkaptonuria or rather congenital ochronosis. PMID- 1734348 TI - Skull base surgery. PMID- 1734349 TI - The posterior ethmoid artery in severe epistaxis. PMID- 1734350 TI - Cervical "tropical" pyomyositis. PMID- 1734351 TI - Verrucous carcinoma. PMID- 1734352 TI - Stereophotography of computer-aided three-dimensional reconstructions of the temporal bone structures. PMID- 1734354 TI - Otitis media. PMID- 1734353 TI - Hearing. PMID- 1734355 TI - Equilibrium. PMID- 1734356 TI - Chemical senses. PMID- 1734357 TI - Hearing and equilibrium. PMID- 1734358 TI - Otitis media. PMID- 1734360 TI - Voice. PMID- 1734359 TI - Airways, allergy, sinus. PMID- 1734361 TI - Head and neck cancer. PMID- 1734362 TI - The Robert Wood Johnson Clinical Scholars Program: a research training plan. PMID- 1734363 TI - The importance of the eosinophil in head and neck cancer. AB - In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for squamous cell carcinoma of the head and neck (p less than 0.05). The present expanded study was undertaken to confirm this finding. The pathology of 120 head and neck tumors was examined for histologic features suggestive of poor prognosis. Ten descriptive histopathologic variables, including two malignancy grading scales, were correlated with DNA flow cytometric data and clinical outcome. No correlation was found between the malignancy grading scales and DNA flow cytometric data or clinical outcome. The present expanded study confirmed with greater statistical significance (p less than 0.001) that high-grade TATE is a favorable prognostic indicator for head and neck cancer. Furthermore, high-grade TATE was associated with the absence of distant metastasis (p less than 0.05). Using a stepwise logistic regression analysis of the clinicopathologic variables in the study, high-grade TATE was the most influential variable affecting clinical outcome, followed by border, stage, and perineural invasion. We conclude that the grade of TATE is a significant prognostic indicator for head and neck cancer. The significance and possible role of the eosinophil in the tumor-host interaction are discussed. PMID- 1734364 TI - Post-tympanostomy otorrhea: a randomized clinical trial of topical prophylaxis. AB - Myringotomy with the insertion of tympanostomy tubes has become the most frequently performed otolaryngologic procedure, and otorrhea is the most common post-tympanostomy complication. Many otolaryngologists routinely use prophylactic topical antibiotic solutions when performing tympanostomy tube placement. Relatively little has been written regarding early post-tympanostomy otorrhea and scarcely any examining the efficacy of such prophylaxis. The current study is a randomized clinical trial to critically evaluate the efficacy of prophylactic otic drops after tympanostomy tube placement. The ototoxic potential of these solutions, combined with constant pressures to decrease medication expenses and eliminate unnecessary use of antibiotics, makes determination of the shortest effective course of application paramount. Subjects were randomized at the time of surgery into one of three groups: one group received no prophylaxis, a second group received gentamicin otic drops immediately after tympanostomy tube placement in the operating room only, and the third group received an additional 48 hours of drops (4 drops in each ear, three times a day). All patients were seen within 2 weeks postoperatively. An overall early post-tympanostomy otorrhea incidence of 8.7% is documented with 12%, 8.8%, and 5.6% for each study group, respectively. While these findings may suggest possible efficacy of topical prophylaxis, a statistically significant difference between the treatment groups was not proved (p = 0.62). Further analysis by subdivision of the patients, on the basis of middle ear cavity finding at the time of surgery, reveals a highly significant statistical association of the occurrence of post-tympanostomy otorrhea in ears having mucoid effusions (p less than 0.001) as compared to ears without effusion or with serous effusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734365 TI - Sinus, nasal airway, allergy. PMID- 1734366 TI - An animal model of chronic tympanic membrane perforation. AB - Previous investigations into the healing and reconstruction of tympanic membrane (TM) perforations have involved animal models with acute TM perforations. A problem with the acute TM perforation model is that most acute TM perforations will heal spontaneously, both in animals and human beings. A second inadequacy of acute perforation models is that they are not analogous to the salient problem in human beings: long-standing TM perforation. The ideal animal model must have a TM perforation that is permanent, well-epithelialized, and free from infection. The perforation must also be subtotal to preserve a rim of membrane for experimental manipulations. In the chinchilla, we have identified a hardy animal with a short, wide ear canal and relatively large tympanic membranes. Thermal myringectomy, followed by medial infolding of TM microflaps, has resulted in permanent, subtotal chronic TM perforations in the chinchilla animal model. Of the 19 chinchillas (38 TMs) perforated, chronic subtotal perforations were created in 32 ears, 6 to 8 weeks after the initial procedure (84% success). Persistent infection or TM regeneration despite reperforation was recorded in 6 ears (16%) failure). This model is currently being used to assess various biomembrane scaffolds impregnated with growth-promoting substances in the regeneration of a physiologically sound TM, initially in our animal model and then in human beings. We envision the development of a biomembrane disc impregnated with biorecombinant growth factors that may provide a simple office technique for the repair of chronic, non-infected TM perforations. PMID- 1734367 TI - Voice. PMID- 1734368 TI - Videolaryngoscopy in the office--a critical evaluation. AB - In view of the growing popularity of office videolaryngoscopy, surprisingly little objective data exist as to its influence on clinical practice. We reviewed 150 consecutive laryngeal recordings in an attempt to determine what effect videolaryngoscopy has had on our practice and the patient care provided. PMID- 1734369 TI - Chemical senses. PMID- 1734370 TI - Transfusion, recurrence, and infection in head and neck cancer surgery. AB - The detrimental effects of transfusion have been documented--particularly by surgical oncologists, who believe transfusion-induced immunosuppression increases the incidence of recurrence and infectious complications. We examined this relation in surgical oncology of the head and neck. After meeting strict inclusion criteria, 104 patients were entered into the study, in which 31 variables of a clinical, surgical, pathologic, laboratory, and treatment nature were studied. Multivariate analysis showed transfusion did not significantly affect recurrence or infectious complications. However, by univariate analysis, infectious complications were related to transfusion (p = 0.029). The variables age (p = 0.024), postoperative hemoglobin level (p = 0.049), and spread to regional lymph node (p = 0.0015) were found to significantly affect the incidence of recurrence. In the three previous otolaryngologic studies, transfusions had been shown to affect recurrence; however, two studies used univariate analysis only. Since this is one of the first otolaryngologic studies to examine the relation of transfusion with infectious complications, prospective studies using multivariate analysis are warranted. Meanwhile, the decision to transfuse should continue to depend on the clinical status of the patient. PMID- 1734371 TI - Bone conduction implants: transcutaneous vs. percutaneous. AB - Clinical experience with transcutaneous bone conduction implants has demonstrated that they are most beneficial for patients with purely conductive hearing loss in at least one ear. Percutaneous bone conduction implants, however, have been reported to provide adequate benefit for patients with mixed hearing loss with bone conduction pure-tone averages up to 45 dB HL (Tjellstrom, 1989). The results of 24 Xomed Audiant osseointegrated bone conduction hearing devices (including a clinical trial on two patients using a new, larger magnet [Neodynium Iron Boron]), plus the results of eleven patients implanted and fitted with the percutaneous bone-anchored hearing aid are reported. Aided results with these devices will be presented. In addition, general comparisons of benefit obtained with the two devices will be made for patients who exhibit similar hearing losses. Finally, a direct comparison will be made on two patients who have undergone both implant procedures. PMID- 1734372 TI - Head and neck oncology. PMID- 1734373 TI - Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis. AB - Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings. PMID- 1734374 TI - Facial nerve disorders. PMID- 1734375 TI - Postoperative risk following uvulopalatopharyngoplasty for obstructive sleep apnea. AB - A study was conducted to assess oxygenation and respiratory changes on the first and second postoperative nights after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA). Twelve patients were postoperatively evaluated with 8-hour nocturnal polysomnography on four occasions: (1) PREOP--night before UPPP, (2) POPN1--first postoperative night, (3) POPN2--second postoperative night, and (4) 3MOS--3-month follow-up study. Results demonstrate that apnea index (AI) and respiratory disturbance index (RDI) were significantly improved at 3MOS from PREOP levels: AI (p less than 0.01) and RDI (p less than 0.05). There were no statistical differences from PREOP to POPN1 or POPN2 for AI, RDI, lowest oxyhemoglobin saturation (LSAT), or number of desaturations (#DESAT). One of twelve patients dropped LSAT greater than 10% from PREOP to POPN1 or POPN2 (82% PREOP to 71% POPN2). Patients were grouped by PREOP LSAT greater than or equal to 80% or less than 80%, and the postoperative change in LSAT was evaluated by comparing PREOP to a value averaging POPN1 and POPN2. Patients with LSAT greater than or equal to 80% decreased by 2.6%; patients with LSAT less than 80% improved by 6.2%. This change in LSAT between groups was statistically different (p = 0.02). These data suggest that in the majority of patients, preoperative indices remain unchanged for at least 2 days after surgery, even for patients who demonstrated improvement at 3 months. However, worsening does occur in some patients. On the basis of the results of this study and clinical experience with the postoperative course, a selective management protocol is outlined. PMID- 1734376 TI - The effect of pentoxifylline on cochlear blood flow. AB - Pentoxifylline, a phosphodiesterase inhibitor and hemorrheologic agent has been found to increase oxygen delivery to ischemic tissue. Intravenous pentoxifylline was administered to normal guinea pigs in order to assess the effect of pentoxifylline on cochlear blood flow and to elucidate its mechanism of action. Intravenous pentoxifylline was found to acutely increase cochlear blood flow in a dose-dependent manner. In normal animals, the effect appeared strongly related to the rheologic properties of this agent rather than a vasodilative action. Normovolemic hemodilution with 75% dextran resulted in no increase in cochlear blood flow during infusion of pentoxifylline, whereas the application of nitroprusside over the round window failed to abolish the effect of pentoxifylline. PMID- 1734377 TI - Facial plastic and reconstructive surgery. PMID- 1734378 TI - Laser surgery. PMID- 1734379 TI - Sudden bilateral profound hearing loss resulting from meningeal carcinomatosis. AB - SBPHL is a rare manifestation of hearing loss. Patients with SBPHL should have a thorough evaluation for meningeal carcinomatosis as the cause, including a complete neurologic evaluation, CT scan, and, probably, MRI. If MC is highly suspected, an LP is necessary. Because the diagnosis of MC can be confirmed only by the presence of malignant cells in the CSF, multiple LPs may be necessary to find them. Although MC should be strongly considered in the differential diagnosis of SBPHL, MC should also be considered with other patterns of eighth cranial nerve involvement, especially in patients with a history of malignancy. These patterns include unilateral hearing loss associated with tinnitus, unilateral hearing loss rapidly progressing to severe bilateral involvement, audiologic and caloric studies that show eighth cranial nerve impairment, and facial nerve palsy associated with hearing loss. The prognosis for MC is poor, although intraventricular chemotherapy and whole brain radiotherapy can provide significant palliation. PMID- 1734380 TI - Salmonella parotitis with abscess formation. PMID- 1734381 TI - Suppression of bilirubin production in the Crigler-Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin. AB - The heme oxygenase inhibitor tin-mesoporphyrin was used to moderate hyperbilirubinemia in two 17-year-old boys with Crigler-Najjar type I syndrome. Both patients had histories of recent, progressive neurological deterioration and plasma bilirubin concentrations on admission to the hospital were 34.5 and 28.5 mg/dL. Throughout hospitalization lasting more than 400 days, both patients underwent 10 hours of phototherapy nightly and consumed constant weight maintaining diets. They were treated with intermittent plasmapheresis and two periods of tin-mesoporphyrin therapy comprising, in the first study period, 40 doses of 0.5 mumol/kg body weight and in the second study period, 70 doses of 1.0 mumol/kg body weight. Plasma bilirubin concentrations were decreased in both patients to varying degrees as was the rebound hyperbilirubinemia which occurs after plasmapheresis. The prolonged treatments with the inhibitor were well tolerated and no progression of the preexisting neurological impairments occurred during the clinical trials. The results of this study suggest that the clinical application of an effective heme oxygenase inhibitor can provide a potentially useful, pharmacological adjunct to presently available therapeutic modalities for controlling episodes of acute, severe jaundice in this but lethal disorder. PMID- 1734382 TI - Vaccine storage practices in pediatric offices. AB - Fifty pediatric offices and clinics in the metropolitan Los Angeles area were visited to assess vaccine storage practices. Questionnaires were administered to the personnel responsible for vaccine storage and the vaccine refrigerators were inspected. Only 16% of vaccine storage coordinators could cite appropriate storage temperatures for vaccines and 18% were unaware that heat can harm certain vaccines. Refrigerator thermometers were checked at least weekly in only 20% of offices, and 22% of the refrigerators had inappropriately high temperatures. Vaccines were routinely stored outside of the refrigerator uninsulated during the practice day in 16% of the offices visited. It is concluded that vaccine storage errors occur in pediatric offices at an unacceptably high frequency. Pediatricians should familiarize themselves with the guidelines for optimal vaccine storage in order to minimize the potential for vaccine failure in primary care practice. PMID- 1734383 TI - Determinants of condom use among junior high school students in a minority, inner city school district. AB - Condoms reduce the risk of human immunodeficiency virus (HIV) transmission; however, their use among adolescents has been inconsistent. Little is known about factors which motivate consistent condom use, particularly among younger adolescents. In a study designed to identify such factors, 1899 inner-city junior high school students were surveyed. In June 1988, students completed an anonymous self-report questionnaire assessing HIV-related knowledge, attitudes, and behaviors. Among sexually active students (N = 403), logistic regression analysis evaluated the influence of demographic, psychosocial, and behavioral factors on frequency of condom use. Respondents who believe condoms are effective in preventing HIV transmission were 2.2 times more likely to report using condoms consistently during sexual intercourse; those with low perceived costs associated with condom use were 1.9 times more likely to be consistent users. Number of lifetime sexual partners was inversely related to frequency of condom use. Respondents with a history of three or more sex partners were half as likely to use condoms consistently. Factors not associated with consistent condom use include age, age at sexual debut, ethnicity, HIV knowledge, perceived efficacy to avoid HIV infection, and alcohol and drug use. School- and community-based HIV prevention programs will have to go beyond the didactic transfer of factual information and include more interactive teaching strategies to improve adolescents' attitudes toward condoms are self-efficacy to increase condom use and to counter negative peer influences and adolescents' perceptions of invulnerability. Physicians are an underutilized source of HIV prevention information. They have an important role in counseling adolescents about effective HIV-prevention methods and dispelling misperceptions which hinder consistent condom use. PMID- 1734384 TI - Intratracheal suctioning, systemic infection, and the meconium aspiration syndrome. AB - A retrospective analysis was performed to determine: (1) the proportion of neonates with the meconium aspiration syndrome (MAS) who were not depressed at birth; (2) to evaluate the clinical course of neonates with MAS, particularly relating to whether or not delivery room intubation and intratracheal suctioning had taken place; and (3) to examine the incidence of culture-proven bacteremia among meconium-stained neonates and those with MAS. The medical records of all meconium-stained neonates and those with MAS admitted to our facility from 1985 through 1989 were reviewed. Of 5697 liveborn neonates, 741 (13%) were meconium stained, of whom 608 (82%) were intubated and suctioned in the delivery room. No complications of the intubation/suctioning procedure were noted in these neonates. Forty-five neonates had culture-proven bacteremia. Five bacteremic neonates had been meconium-stained (0.7% of all such neonates), while 40 were not stained (0.8% incidence). Of 36 neonates with MAS, 1 (2.8%) was bacteremic. Twenty (56%) of 36 newborns with MAS did not require positive pressure ventilation in the delivery room. Twelve (33%) of the babies with MAS had not been intubated and suctioned in the delivery room. Nine (75%) of 12 nonsuctioned neonates, as well as 6 (25%) of 24 suctioned neonates, required mechanical ventilation for more than 6 hours (P = .010). Pneumothoraces occurred in 6 (50%) of 12 nonsuctioned and 5 (21%) of 24 suctioned babies (P = .125). Four of 12 nonsuctioned newborns either died (n = 1) or required extracorporeal membrane oxygenation (n = 3), while only 1 of the suctioned newborns required extracorporeal membrane oxygenation (P = .034).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734385 TI - Localization of human immunodeficiency virus core antigen in term human placentas. AB - Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734386 TI - Cost-effectiveness of erythromycin versus mupirocin for the treatment of impetigo in children. AB - A new topical antibiotic, mupirocin, has been found to be as effective as erythromycin for the treatment of impetigo, but concerns about its expense have been raised. This controlled clinical trial sought to compare the cost effectiveness of erythromycin (E) and mupirocin (M). Ninety-three children, aged 3 months to 16 years, were randomly assigned to receive 10 days of oral erythromycin (n = 46) or topical mupirocin (n = 47). Costs and effects were measured through structured interviews. Cost per case differed significantly by group (E = $56.85; M = $62.30; P less than .05) due chiefly to extra visits and medication changes needed by those treated with mupirocin. Erythromycin and mupirocin were equally effective. The likelihood of side effects (E = 43%, M = 22%) approached significance (P less than .07); those treated with erythromycin were willing to pay more for a different medicine to avoid the side effects experienced (P less than .05). Working parents and school-age children were more likely to alter their daily activities when the patient was taking erythromycin (P less than .04). Compliance and parental satisfaction did not differ by treatment group; however, parents of children treated with erythromycin were more likely to prefer the alternate drug regimen. It is concluded that the type of medication prescribed can be based on parental preference because the increased cost of mupirocin is offset by increased side effects and number of schooldays and workdays lost with erythromycin. PMID- 1734387 TI - Adaptation of feeding to a low fat yield in breast milk. AB - The effect of a low milk fat yield was assessed in a blinded prospective study of healthy term infants and mothers encouraged to breast-feed. Fat yield index was calculated as milk volume collected by Egnell pump multiplied by the "creamatocrit." Two weeks after delivery mothers who had a relatively low fat yield index (less than or equal to 30th percentile) were matched with mothers with a higher fat yield index and with formula-feeding mothers. Between 2 and 6 weeks the low fat yield group had a marginally lower weight gain but similar growth in length and head circumference to that of the higher fat yield group. The low fat yield group spent more time per feeding and had more complete breast emptying, resulting in a fat yield index comparable with the higher fat yield group for the mean milk volume ingested by the infant at 6 weeks. A low fat yield had no adverse effect on maternal satisfaction or maternal-infant interaction during feeding. Formula feeders spent the least time in feeding and en face gazing. Adaptation of breast-feeding to a low fat yield sustains infant intake and growth, maternal-infant interaction, and maternal satisfaction. However, there is little reserve if milk production diminishes. Further study is needed to define the limits of adaptation and effective interventions if fat yield is inadequate. PMID- 1734388 TI - Nutrient adequacy of low fat intakes for children: the Bogalusa Heart Study. AB - Nutritional adequacy is important when diets and dietary alterations are recommended for children. Concern is expressed that low fat intakes may have deleterious effects on growth and development and may be deficient in total calories and essential nutrients. In a study of the effect of variation in percent fat in the diet, a sample of 871 ten-year-olds was stratified according to four different fat intakes: less than 30% of total kilocalories (kcal), 30% to 35% kcal, 35% to 40% kcal, and greater than 40% kcal. The race/sex distribution was similar within each fat intake group. Fourteen percent of the sample had fat intakes less than 30% of total calories. The amount of calories from breakfast, dinner, and snacks was higher in the children with fat intakes greater than 40% of total calories than those with lower fat intakes. The energy intake of all race/sex groups fell within the recommended range. The low fat intake group was eating 25% less calories than the high fat intake group (1800 kcal vs 2400 kcal). The percentage of calories from carbohydrate, specifically sugar, was greater in the low fat intake group compared with the high fat intake group. Percentage of calories from protein was approximately 13% for all groups. Fiber and starch were the same across all fat intakes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734389 TI - Symmetric cerebral blood flow in newborns who have undergone successful extracorporeal membrane oxygenation. AB - Cerebral blood flow (CBF) was measured with positron emission tomography in 23 newborns following extracorporeal membrane oxygenation. In 9 newborns the common carotid artery was reanastomosed after extracorporeal membrane oxygenation and in 14 newborns the common carotid artery remained ligated. The ratio of right/left hemispheric CBF was not significantly different in the newborns with reanastomosed or occluded common carotid arteries (right/left CBF ratio was 0.98 in both groups). The maximum asymmetry was 8% and was observed in 2 newborns. All 9 newborns with reanastomosis of the carotid artery are normal at follow-up at 1 year or longer. Three newborns with ligation of the common carotid artery were lost to follow-up and 1 newborn died. Eight of 10 remaining newborns are normal at follow-up; the 2 other infants have developmental quotients of 60 and 64, respectively, and no other deficits. The data indicate (1) that hemispheric CBF is symmetric in newborns who have undergone extracorporeal membrane oxygenation and have no evidence of brain injury, and (2) that reanastomosis of the common carotid artery does not alter hemispheric CBF in the newborn period. PMID- 1734390 TI - Lupus nephritis: prognostic factors in children. AB - As newer treatment modalities become available for patients with severe lupus nephritis, it becomes increasingly important to identify patients at risk for renal failure. In this study, the records of 90 children presenting with systemic lupus erythematosus over a 13-year period were reviewed. Nineteen were lost to follow-up prior to completion of the study. Of the 71 remaining children, 16 (22%) progressed to chronic renal failure. Persistent hypertension lasting greater than 4 months, anemia, abnormalities of the urinalysis, and elevated serum creatinine level were significantly associated with progression to renal failure. Sex, race, age, abnormalities of creatinine clearance, and 24-hour urine protein collection were not associated with progression to renal failure. Renal biopsies were obtained in 45 children. Biopsies were initially classified according to World Health Organization criteria. Diffuse proliferative glomerulonephritis was significantly associated with progression to renal failure. The 45 biopsies available were reviewed by one of the authors and categorized by activity and chronicity indices. Both the active lesions of fibrinoid necrosis, synechiae, tubular casts, and vasculitic lesions and the chronic lesion of glomerular sclerosis correlated with progression to renal failure. Of the 16 children who progressed to renal failure, 2 had cadaver kidney transplants and are well 5 years posttransplant; 4 had fulminant lupus and died within 1 month of commencing dialysis; 10 began chronic dialysis. Five of the 10 children on chronic dialysis died from sepsis. These data suggest that children with systemic lupus erythematosus who undergo dialysis do poorly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734391 TI - Cerebrospinal fluid isoniazid concentrations in children with tuberculous meningitis: the influence of dosage and acetylation status. AB - Cerebrospinal fluid (CSF) and plasma isoniazid (INH) concentrations were determined on 96 occasions in 38 children (median age 1.5 years) with tuberculous meningitis, and the effects of INH elimination status and test dosages of 10 mg/kg body weight and 20 mg/kg body weight was studied. Maximum cerebrospinal fluid INH concentrations were reached during the period 2 to 4 hours after dosing and cerebrospinal fluid and plasma INH concentrations did not differ significantly during this period. Cerebrospinal fluid INH concentrations following a dosage of 10 mg/kg (4.6 +/- 2.4 micrograms/mL) were, however, significantly lower than those following a dosage of 20 mg/kg (11.6 +/- 2.7 micrograms/mL). Cerebrospinal fluid INH concentrations in faster acetylators at a dosage of 10 mg/kg (3.2 +/- 1.1 micrograms/mL) were significantly lower than in slower acetylators (7.7 +/- 1.3 micrograms/mL), as was the case with a dosage of 20 mg/kg, where faster acetylators had cerebrospinal fluid INH concentrations of 10.5 +/- 2.5 micrograms/mL compared with 14.1 +/- 1.4 microgram/mL in slower acetylators. Following dosages of both 10 mg/kg and 20 mg/kg, INH concentrations in excess of the minimal inhibitory concentration for Mycobacterium tuberculosis persisted in the CSF 12 to 14 hours later. Despite the patients' being young and frequently malnourished, suffering from advanced forms of tuberculous meningitis, and receiving high dosages of INH, rifampicin, and pyrazinamide, none developed any clinical signs of hepatotoxicity and in only one child did the serum bilirubin level rise to 19 micrograms/mL. PMID- 1734392 TI - Rapid improvement in the renal tubular dysfunction associated with tyrosinemia following hepatic replacement. AB - The postoperative management of patients with hereditary tyrosinemia type I (McKusick 27670) following liver transplantation is often complicated by the renal tubular dysfunction associated with this disease. To characterize better the temporal course of the improvement in renal excretory activity following hepatic replacement, renal tubular function and metabolite excretion were studied in a 4-year-old girl with hereditary tyrosinemia during the immediate post transplantation course. Tubular reabsorption of bicarbonate and phosphate were normal 5 days following transplantation, in contrast to glucosuria, hyperaminoaciduria, and tyrosyluria, which persisted for approximately 3 weeks. After hepatic replacement, serum amino acid concentrations returned to normal and succinylacetone was no longer detected in the urine. This is the third tyrosinemia patient reported to achieve complete resolution of urinary abnormalities following transplantation, and the only patient in whom renal tubular function was formally assessed within the first postoperative week. PMID- 1734393 TI - Heart rate monitoring of physical activity in children and adolescents: the Muscatine Study. AB - To assess the usefulness of whole-day heart rate monitoring as a quantitative measure of physical activity in children, the activity of 76 children and adolescents (ages 6 to 17 years), randomly selected from a school population, was measured during a typical summer day using a light-weight, nonrestrictive heart rate telemetry unit. A 12-hour recall and a simple self-rating of usual activity questionnaire were also administered on the same day. An additional 12-hour recall questionnaire was administered on another day. Within 1 month of the heart rate monitoring, the skinfold measures, peak aerobic capacity, and sexual maturation were assessed. Data analysis indicated that activity as measured by telemetry was related to questionnaire recall on the monitored day (r = .50), nonmonitored day (r = .32), and self-rating (r = .35); level of activity as measured by telemetry was related to peak aerobic capacity in girls (r = .36) but not in boys (r = -.06); body fat was related inversely to activity (r = -.32); and prepubescent children were more active than post- and pubescent children (P less than .003). No difference was found in activity level between boys and girls (P greater than .05). This study suggests that for children whole-day heart rate monitoring is an objective, nonobtrusive method for measuring physical activity; and maturation, but not gender, is an influential mediating factor for activity. PMID- 1734394 TI - Increased familial cardiovascular mortality in obese schoolchildren: the Muscatine Ponderosity Family Study. AB - Total and cause-specific mortality was investigated in 387 first- and second degree deceased adult relatives of three groups of children selected from those who participated in three biennial school surveys in Muscatine, Iowa: the lean group (students in the first quintile of relative weight on all three surveys); the random group (a random sample of all eligible students); and the heavy group (students in the fifth quintile of relative weight on all three surveys). A greater proportion of death certificates for heavy group relatives listed a cardiovascular cause of death (60%) compared with lean (48%) and random (43%) group relatives. The relative risk of dying of cardiovascular disease for heavy group vs random group relatives was 1.41 (95% confidence interval 1.01, 1.98). In a subset of heavy group families identified by children with elevated systolic blood pressure, the proportion of death certificates listing a cardiovascular cause was even higher (76%) and the estimate of relative risk vs random group relatives was 2.20 (95% confidence interval 1.43, 3.37). These results indicate that persistent obesity in children, particularly when accompanied by persistent blood pressure elevation, identifies families whose members are at increased risk of dying of cardiovascular disease. PMID- 1734395 TI - Horizontal transmission of hepatitis B virus infection to United States-born children of Hmong refugees. AB - There is evidence that hepatitis B virus (HBV) transmission continues among Southeast Asian refugees after resettlement. To determine the prevalence of HBV infection (hepatitis B surface antigen [HBsAg] positive or core antibody positive) and modes of transmission in Hmong refugee households in Wisconsin, results of serologic tests were reviewed for 429 US-born children not previously vaccinated with hepatitis B vaccine and 754 of their Asian-born household members. The prevalence of HBV infection was 14% (62/429) among all US-born children, 30% (21/69) among children whose mothers were HBsAg-positive, and 11% (41/360) among children whose mothers were HBsAg-negative. Among children whose mothers were HBsAg-negative, the prevalence of HBV infection increased with increasing age (chi 2 test for trend = 5.6, P = .02) and was related to the household presence of HBsAg-positive sibling(s) (relative risk = 4.0; 95% confidence interval = 1.5, 9.3; P less than .001). Of the 62 infected children, 13 (21%) lived in households with no HBsAg-positive household members. US-born children of Hmong refugees apparently acquire HBV infection through both horizontal and perinatal transmission. These findings emphasize the importance of routinely integrating hepatitis B vaccine doses into the childhood vaccination schedule for all infants whose parents are from areas where HBV infection is highly endemic. In addition, the findings support the need for pediatricians to consider vaccinating older children (up to age 7 years) whose parents are from HBV-endemic areas. PMID- 1734396 TI - Markers for occult liver injury in cases of physical abuse in children. AB - Children suffering physical abuse are at risk for abdominal trauma. When the abdominal trauma is not evident clinically and remains occult, the child's condition can rapidly deteriorate before the diagnosis is made, and delay may occur in the activation of child protective services. The use of markers for abdominal trauma in the evaluation of cases of child physical abuse was examined. Children younger than 12 years presenting to the Emergency Department at the Children's Hospital of Buffalo from August 1989 through April 1990 for the evaluation of suspected physical abuse were prospectively entered in the project. All patients had a complete history and physical examination performed. Those patients who did not show any signs of abdominal injury had the following laboratory tests done: (1) levels of liver transaminases, lactate dehydrogenase, and alkaline phosphatase; (2) amylase level; and (3) uranlysis. Of 49 patients without clinical signs of abdominal trauma, 4 children had elevated transaminase levels. Three of these 4 patients had liver lacerations documented by subsequent abdominal computed tomographic scans. A new finding of transaminase levels as markers of occult liver injury in children suffering physical abuse is reported. PMID- 1734397 TI - Parasitology screening of Latin American children in a primary care clinic. AB - A screening program based in a Massachusetts community hospital primary care clinic, which included 124 children from 12 different Latin American countries, demonstrated that nearly 35% were carriers of pathogenic parasites. The large majority (83.7%) of these children were asymptomatic at the time of the examination. Although there may be considerable variation based on country of origin, the present results, as well as a review of the literature, suggest this is likely to be a common finding among children born in most regions of Latin America. Compliance with the screening process was significantly higher in groups with higher infection rates and the successive yield in those patients who submitted two or more stool samples revealed that most pathogens were identified in the first sample. School-age children were found to have the highest risk for both roundworm infections and multiple parasitic infections. For those children with identified pathogens, nearly 90% received treatment. Current trends in immigration, international adoptions, and special circumstances including day care, family shelters, and increasing numbers of human immunodeficiency virus infected children have made an appreciation of the extent of parasitosis, and awareness of possible management approaches, an important consideration for primary care physicians in the United States. PMID- 1734398 TI - Estimating infant mortality from human immunodeficiency virus and other causes in breast-feeding and bottle-feeding populations. AB - This paper discusses the literature dealing with breast-feeding in women with human immunodeficiency virus (HIV) infection. This review is used to develop a background for a quantitative assessment of factors determining whether breast feeding or bottle-feeding will result in a lower overall mortality in areas of different HIV prevalence. An algebraic formula is presented that enables calculation of the mortality that would result in any population if the following variables are known or capable of estimation: portion of childbearing women infected with HIV, portion of newborns infected with HIV at birth, relative mortality of breast-fed and bottle-fed infants that are not HIV infected, and transmissibility of HIV during breast-feeding. The information available for estimating these variables is incomplete. Nevertheless, boundaries can be set for each variable, based on information obtained locally or from the literature, to aid in objective evaluation of the risks of promoting bottle-feeding or breast feeding in populations with different risk characteristics. Consideration of these factors indicates that the benefits of breast-feeding over bottle-feeding can substantially outweigh any putative risk of HIV transmission during breast feeding unless the prevalence of HIV infection is quite high or the difference in mortality of breast-fed and bottle-fed infants is very low. PMID- 1734399 TI - Thymic abnormalities in fetuses aborted from human immunodeficiency virus type 1 seropositive women. AB - Pathological abnormalities of the thymus were found in 3 of 37 fetuses aborted from human immunodeficiency virus (HIV)-infected mothers. These lesions were located predominantly in the thymic cortex, which contains mostly immature lymphocytes. Areas of focal lymphocyte depletion were infiltrated with CD4+ macrophages and were associated with abnormalities of the epithelial stromal network. No evidence of extensive HIV infection in any of the 37 thymuses was detected by either immunofluorescence or in situ hybridization techniques, although rare cells that expressed HIV antigens were found in 3 fetuses. Although less extensive, this thymic fetopathy was similar to that described in postnatal acquired immunodeficiency syndrome thymuses, strongly suggesting that the lesions were related to HIV infection. Thymic fetopathy might represent the initial injury to the lymphoid system in HIV-infected infants in whom early and severe immunosuppression develops. PMID- 1734400 TI - Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). AB - Aerosolized racemic epinephrine, but not L-epinephrine, is commonly used in treating croup. The efficacy and adverse effects of nebulized racemic and L epinephrine in the treatment of laryngotracheitis were compared. Children 6 months to 6 years of age with a croup score of 6 or above were assigned in a randomized double-blind fashion to receive either racemic (n = 16) or L epinephrine (n = 15) aerosols. Croup score, heart rate, blood pressure, respiratory rate, fraction of inspired oxygen, and oxygen saturation were recorded before treatment and at 5, 15, 30, 60, 90, and 120 minutes after the aerosol. Patients in both groups showed significant transient reduction of the croup score and respiratory rate following the aerosol (P less than .001), but there were no differences between treatment groups when croup score, heart rate, blood pressure, and respiratory rate were assessed over time. It is concluded that L-epinephrine is at least as effective as racemic epinephrine in the treatment of laryngotracheitis and does not carry the risk of additional adverse effects. L-Epinephrine is also more readily available worldwide, is less expensive, and can be recommended for this purpose. PMID- 1734401 TI - Genital injuries resulting from sexual abuse: a longitudinal study. AB - Three children who incurred genital injuries as a result of sexual assaults were followed up on a longitudinal basis to document the anatomical changes which ensued. The subjects, who were 4 months, 4 years 5 months, and 9 years of age, were followed up for periods ranging from 14 months to 3 years. A multi-method examination approach and a 35-mm camera mounted on a colposcope were used to examine and record their injuries. Signs of the acute damage disappeared rapidly, and the wounds healed without complications. Following the resolution of the acute injuries, the changes created by the trauma remained relatively stable throughout the prepubertal years. The most persistent findings were irregular hymenal edges and narrow rims at the point of the injury. Over time the jagged, angular margins smoothed off. Disruption of the hymen exposed underlying longitudinal intravaginal ridges whose hymenal attachments created mounds or projections. There was little apparent scar formation. Even the injuries to the posterior fourchettes healed with minimal scar tissue and left only the slightest evidence of the trauma. With the onset of puberty, the hymenal changes in the oldest subject were obscured by the hypertrophy of this membrane. An examination technique which used a Q-tip to separate the redundant tissues demonstrated that the signs of trauma had survived. PMID- 1734402 TI - The ricochet of magic bullets: summary of the Institute of Medicine Report, Adverse Effects of Pertussis and Rubella Vaccines. PMID- 1734403 TI - Finger intubation of the trachea in newborns. PMID- 1734404 TI - Intraventricular hemorrhage in the full-term neonate associated with abdominal compression. PMID- 1734405 TI - Idiopathic neonatal hepatitis in one DNA fingerprint identical twin. PMID- 1734406 TI - Not all severe hyperglycemia is diabetes. PMID- 1734407 TI - Magnetic resonance imaging evaluation of neonates with retinal hemorrhages. PMID- 1734408 TI - How safe are pertussis and rubella vaccines? A commentary on the Institute of Medicine Report. PMID- 1734409 TI - American Academy of Pediatrics, Committee on Communications: The commercialization of children's television. PMID- 1734410 TI - The other view of disposable diapers. PMID- 1734411 TI - Mental retardation and ADHD! PMID- 1734412 TI - Fire hydrant injuries. PMID- 1734413 TI - Fire hydrant injuries. PMID- 1734414 TI - Developmental toxicants risk assessment. PMID- 1734415 TI - Life, death, and parents' opinions in the intensive care unit. PMID- 1734416 TI - Risks with translocation in "typus edinburgensis". PMID- 1734417 TI - Publish or perish. PMID- 1734418 TI - More on dog-bite injuries. PMID- 1734419 TI - Very low birth weight outcomes. PMID- 1734420 TI - Very low birth weight outcomes. PMID- 1734421 TI - Iron syrup concentration error. PMID- 1734422 TI - Pediatricians do matter. PMID- 1734423 TI - [Fever is children]. AB - Fever is a common symptom in childhood, and is often a sign of innocuous infection. Although most children with serious infections are diagnosed at clinical examination, there are important exceptions that should be borne in mind by all physicians. The article provides advice as to when parents ought to consult a physician in cases of childhood fever, and on the use of antipyretics. PMID- 1734424 TI - [Prediction of cancer mortality in Scandinavia in 2005. Effect of various interventions]. AB - Approximate estimates have been made of the effect by the year 2005 of various preventive measures to reduce cancer mortality in Scandinavia. Figures have been calculated for changes in smoking, diet and exposure to sunlight (primary prevention), for earlier diagnosis (secondary prevention), and improved survival as a result of improved treatment (tertiary prevention). The calculations have been performed with the American program CAN TROL, the effect being expressed as the percentage reduction in cancer mortality by the year 2005. The results give promise of a substantial overall reduction in cancer mortality in Scandinavia. PMID- 1734425 TI - [fever!]. PMID- 1734426 TI - [Swedish public health report 1991. Increasing social consequences of illness?]. AB - According to the Swedish Public Health Report of 1991, health has improved in the 45-64-year-old age group of the gainfully employed population during the 1980s. Cardiopulmonary and gastrointestinal diseases have become less common, whereas certain types of cancer, allergy, and locomotor pain are on the increase. The prevalence of locomotor pain among young working women has doubled. The number of those on early pensions is increasing, which may be due to increasing demands in the working environment as well as to organisational re-structuring. The report points out that the chronically ill and those on disability pensions are finding it harder to compete in the housing market. A medical class distinction is made: those with long-term mental illness have a much worse standard of living than those with somatic diseases. PMID- 1734427 TI - [Unemployment and ill health]. PMID- 1734429 TI - [Education proposal for physicians in sparsely populated areas]. PMID- 1734428 TI - [Unemployment and ill health--or the other way around?]. AB - In response to a recent article in Nord Med (No 11/91) this paper raises a critique of the reanalysis of two Nordic studies on the effects of unemployment on health: The model based on varying relationships between vocational ability and job requirement does not invalidate earlier findings. However, the interpretation of measurements of health in individual based follow-up studies warrants a discussion, as well as the external validity of their findings. Unemployment has been shown to affect health related behaviour, like consultation rates, referrals, sick leave and disability pension, in well controlled studies. These effects are of importance to the individuals and the health- and social services, regardless of their relation to disease in a biomedical sense. PMID- 1734430 TI - [A glimpse of Estonia's health services]. PMID- 1734431 TI - [Fever--friend or foe?]. AB - Since the turn of the century intensive research has been carried out to ascertain whether fever is associated with the organism's defence against microbial agents, and evidence is now available concerning the beneficial impact of fever under certain circumstances. However, fever also often gives rise to risks and inimical sequelae. Antipyretics should be used in the correct manner, and when the fever constitutes a hazard to the patient or causes suffering. PMID- 1734432 TI - [Temperature measurement--where, when and how?]. AB - The mercury thermometer may no longer be sold in Sweden, and is soon to be proscribed in the other Scandinavian countries. How reliable are other thermometers, and should body temperature be measured orally, rectally or in some other way? PMID- 1734433 TI - [How do people perceive fever and what is done for it?]. AB - The perception of fever has changed throughout history. Fever is a common symptom, and nowadays antipyretics are widely used. However, our knowledge of layman's perception of fever and self-care is rather limited. Unfounded parental concern of fever in children ("fever phobia") has not been found in Nordic studies. However, the findings indicate a need for more definite and consistent information on fever and fever management, including self-medication. This is a joint challenge to primary health care workers and local pharmacists. PMID- 1734434 TI - Infancy problem behaviors. AB - The goal of pediatric health supervision is to promote the optimal growth and development of children. Parent-infant interaction and parental attitudes toward their infant are important determinants of child development. Anticipatory guidance during child health supervision enables the pediatric provider to discuss developmental stages and demystify common stage-related behaviors, such as fussing, night-waking, repetitive movements, and clinging. Anticipating the emergence of such behaviors and issues may lessen parental anxiety and concern. When behavioral problems such as colic or sleep difficulties do arise, a consideration of developmental stage is helpful in suggesting specific management strategies. The successful implementation of developmentally-oriented approaches has benefits for the family and pediatric provider, including increased parental self-confidence, enhanced family functioning, and increased parental confidence in the pediatrician. Furthermore, by encouraging developmentally-oriented approaches, parents will be less inclined to adopt inappropriate or ineffectual behavioral management strategies. PMID- 1734435 TI - Otitis media. PMID- 1734436 TI - Left upper quadrant masses in children. PMID- 1734437 TI - Pickles, pizza, and PREP. PMID- 1734438 TI - Case 1 presentation. Sickle cell sequestration crisis. PMID- 1734439 TI - Case 2 presentation. Salicylate toxicity. PMID- 1734440 TI - Case 3 presentation. Congestive heart failure in an infant. PMID- 1734441 TI - Screening for vision problems in pediatric practice. PMID- 1734442 TI - Amblyopia: etiology, detection, and treatment. AB - Amblyopia is a preventable cause of visual loss in children that may be permanent unless it is detected and treated early. It may be caused by strabismus, refractive errors, or cataracts. Primary strabismus may lead to loss of vision from amblyopia and the loss of binocularity. Secondary strabismus may be a sign of primary visual loss in one or both eyes. The most serious disorder that may present as secondary strabismus is retinoblastoma. It is imperative to detect retinoblastoma early because of its morbidity and mortality. Amblyopia is detected by assessing the visual acuity of each eye. Strabismus is detected by using the corneal light reflex test and the cover test. Focusing problems are detected by assessing the visual acuity and the red reflex. Cataracts and retinoblastoma may be detected by examining the red reflex of the eye. Treatment of amblyopia consists of correcting the amblyogenic factor with appropriate glasses and surgery. The preferred eye is patched with an adhesive patch to stimulate visual development in the amblyopic eye. The pediatrician plays a crucial role in the early detection of amblyopia, strabismus, and cataracts. The key to successful visual outcome is early recognition by the pediatrician, referral to the pediatric ophthalmologist, and prompt treatment. PMID- 1734443 TI - Vascular response to radiation injury in the rat lung. AB - Changes in relative left-to-right lung blood flow ratios were followed as an index of vascular radiation injury in left-hemithorax-irradiated Sprague-Dawley rats. Single doses of 11 to 21 Gy gamma radiation resulted in a dose-dependent decrease in relative blood flow to the irradiated lung from 3 to 5 weeks after exposure during the development of pneumonitis. Blood flow returned to near normal by 5 weeks after lower doses (11-13.5 Gy). After a single dose of 15 Gy the left-to-right blood flow ratio recovered to 75% of normal at 12 weeks and leveled off. Following 18 Gy irradiation a second period of reduced flow began 16 weeks after exposure. After 21 Gy irradiation flow to the irradiated side remained low for 1 year after exposure. Rats that received a single dose of 18 Gy to the left hemithorax were also treated with one or two of the following drugs: captopril, cyproheptadine, dexamethasone, diethylcarbamazine, penicillamine, or theophylline. Dexamethasone was most effective at preventing the decrease in blood flow to the irradiated lung when treatment was continued through the pneumonitis period and dose was not tapered until 8 weeks after radiation exposure. All other drugs and drug combinations were, for the most part, virtually ineffective after the pneumonitis period. There was a relatively poor correlation with earlier vascular permeability surface area product studies. This suggests that endothelial damage, as well as damage to other cell types, contributes to the development of post-irradiation fibrosis in the lung. PMID- 1734444 TI - Effects of v-src oncogene activation on radiation sensitivity in drug-sensitive and in multidrug-resistant rat fibroblasts. AB - Recent work has implicated the activated ras oncogene, whose gene product is a G protein located in the plasma membrane, as well as the activated raf oncogene, whose gene product is a membrane-associated protein kinase, in contributing to radioresistance. Another transforming oncogene whose gene product is localized to the plasma membrane is v-src. We have examined a rat fibroblast line (RAT-1) infected with an avian sarcoma virus carrying a temperature-sensitive mutation in the v-src tyrosine kinase domain (LA-24). At 40 degrees C, LA-24 cells have a flat morphology and grow as a contact-inhibited monolayer, while at 35 degrees C, LA-24 cells have a transformed morphology, lose contact inhibition, grow in soft agar, and exhibit 3.5-fold higher tyrosine kinase activity. The parental RAT-1 line, not infected by the virus, grows at both temperatures as a contact inhibited monolayer. This well-characterized system represents a good model for examining the effect of v-src transformation on radiosensitivity. RAT-1 and LA-24 cells grown at 35 and 40 degrees C were irradiated with graded doses of radiation, and clonogenic survival was assayed. For LA-24 cells grown at 35 and 40 degrees C, and for RAT-1 cells grown at 35 and 40 degrees C, calculated D0, n, alpha, and beta values did not differ significantly. To determine whether there might be differences in radiation damage repair capacity too subtle to detect by comparing radiation survival curves, sublethal damage repair capacity was assessed. There was no difference in sublethal damage repair capacity for LA-24 cells grown at 35 or 40 degrees C. Other studies have associated multidrug resistance with radioresistance. We have examined the radiation sensitivity of two colchicine-resistant LA-24 clones with four- to fivefold amplification of the P-glycoprotein gene, which are four-to fivefold more resistant to colchicine than the parental LA-24 line. In these multidrug-resistant clones, v-src activation does appear to increase radiation resistance. This did not appear to be due to alteration in cell cycle kinetics. We conclude that oncogene activation, or even protein kinase activity per se, does not necessarily lead to radiation resistance. Rather, radiation resistance following oncogene activation depends upon the oncogene and cell line studied, and perhaps upon specific protein phosphorylation. PMID- 1734445 TI - Differences in effects of oncogenes on resistance of gamma rays, ultraviolet light, and heat shock. AB - The effects of viral or activated cellular oncogenes on sensitivity to gamma rays, ultraviolet light, and heat shock were examined in SHOK (Syrian hamster Osaka-Kanazawa) cells and their transfectants. Resistance to gamma rays was conferred by the introduction of v-mos or c-cot genes, which coded serine/threonine kinase. Cells transfected with v-mos and c-cot genes increased their resistance to ultraviolet light and heat shock compared to their parent cells (SHOK cells). Of the activated ras genes, the N-ras gene developed a SHOK cell phenotype resistant to gamma rays and ultraviolet light. The Ha-ras gene produced SHOK cells resistant to ultraviolet light and heat shock, while introduction of the Ki-ras gene did not affect sensitivity. The v-erbB gene was found to be involved in the development of resistance to heat shock. Transfection with neo, c-myc, and v-fgr genes had little or no effect on cell survival. The karyotypes of SHOK cells and oncogene-containing cells were compared. No alterations were seen after the introduction of a foreign gene. Using cell cycle analysis, we found no apparent difference between SHOK cells and their transfectants. These results suggest that activation of serine/threonine kinase may be involved in common processes occurring after gamma-ray, ultraviolet-light, and heat-shock treatment, and that each oncogene may have a different effect on the development of a resistant phenotype. PMID- 1734446 TI - Leptomycin B-induced fixation of X-ray-related potentially lethal damage. AB - Effects of an antifungal antibiotic, Leptomycin B (LMB), on X-ray cell killing were studied using cultured mammalian cells (BHK21). LMB at concentrations from 0.05 to 2 ng/ml inhibited cell proliferation but enhanced cell killing without significant cytotoxic effect when added to cell cultures pre- and postirradiation. The degree of enhanced cell killing decreased as the interval between irradiation and LMB treatment was prolonged. Enhancement of cell killing was probably due to fixation of potentially lethal damage (PLD) to LMB. Radioresistant S-phase cells were more sensitive to LMB-induced PLD fixation than G1-phase cells. Furthermore, a preliminary study showed that LMB not only inhibited the repair of PLD which was induced by conditioned medium but also inhibited splitdose repair of sublethal damage. Although the target molecule of LMB has not been identified, we suggest that LMB inhibits repair processes by altering the structure of the nuclear scaffold, which is supposed to be a radiosensitive site. PMID- 1734447 TI - Charged-particle mutagenesis. 1. Cytotoxic and mutagenic effects of high-LET charged iron particles on human skin fibroblasts. AB - Cytotoxic and mutagenic effects of high-LET charged iron (56Fe) particles were measured quantitatively using primary cultures of human skin fibroblasts. Argon and lanthanum particles and gamma rays were used in comparative studies. The span of LETs selected was from 150 keV/microns (330 MeV/u) to 920 keV/microns (600 MeV/u). Mutations were scored at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus using 6-thio-guanine (6-TG) for selection. Exposure to these high-LET charged particles resulted in exponential survival curves. Mutation induction, however, was fitted by the linear model. The relative biological effectiveness (RBE) for cell killing ranged from 3.7 to 1.3, while that for mutation induction ranged from 5.7 to 0.5. Both the RBE for cell killing and the RBE for mutagenesis decreased with increasing LET over the range of 1.50 to 920 keV/microns. The inactivation cross section (sigma i) and the action cross section for mutation induction (sigma m) ranged from 32.9 to 92.0 microns2 and 1.45 to 5.56 X 10(-3) microns2; the maximum values were obtained by 56Fe with an LET of 200 keV/microns. The mutagenicity (sigma m/sigma i) ranged from 2.05 to 7.99 X 10(-5) with an inverse relationship to LET. PMID- 1734448 TI - Protein synthesis in irradiated cells. I. Ultraviolet radiation. AB - Excision-deficient haploid yeast cells (Saccharomyces cerevisiae) were exposed to 254-nm UV radiation and protein synthesis inhibition was measured for a large number of different proteins resolved by two-dimensional gel electrophoresis. The derived UV-radiation sensitivities exhibited an overall increase with protein molar mass. Quantitatively, this behavior is compatible with a well known mechanism of transcription inactivation--termination of RNA chains at UV radiation-induced pyrimidine dimers--if the respective target sizes are inferred from protein molar mass. The observed deviations from the predicted response suggest that (i) UV-radiation damage may also interfere with recognition/binding of RNA polymerase to regulatory sequences and (ii) the frequency of photolesions for a specific protein encoding gene may differ markedly from the mean induction rate for the total yeast genome. PMID- 1734449 TI - Chromatin compaction and the efficiency of formation of DNA-protein crosslinks in gamma-irradiated mammalian cells. AB - Chromatin has been prepared from Chinese hamster V79 cell nuclei by successive suspension and sedimentation in buffers of decreasing ionic strength. For buffer concentrations from 50 to 1 mM, the resultant chromatin maintained a normal histone content, nucleosomal organization, and attachment to the nuclear matrix; however, as the buffer concentration was reduced from 50 to 10 and 1 mM, the higher-order chromatin structures became increasingly relaxed. Fully expanded chromatin is 5- to 10-fold more susceptible to the induction of DNA-protein crosslinks (DPCs) by gamma radiation than is chromatin residing in living interphase cells. As much as 60-70% of expanded chromatin can be induced to form DPCs as compared to a maximum of about 20% of cellular DNA. For expanded chromatin, the maximum level of induced DPCs is two to three times higher than would be expected if only matrix-associated DNA were induced to form DPCs. Therefore, DNA in distal regions of chromatin loops must also be induced to form DPCs with histones or other nonhistone chromosomal proteins. The hypersensitivity of isolated chromatin to radiation-induced production of DPCs appears to be related to the expansion of chromatin conformation rather than to the removal of intracellular radical scavengers for the following reasons: (a) there is an inverse relationship between the buffer concentration in which the chromatin is suspended and DPC formation, and (b) the induction of a more compact 30-nm chromatin fiber from the expanded 10-nm chromatin fiber in the presence of a low concentration of MgCl2 results in a marked reduction in DPC formation. The formation of radiation-induced DPC seems to occur at maximum efficiency in fully expanded chromatin, since DPC formation cannot be further stimulated by the addition of Cu2+, which can catalyze the production of OH by Fenton chemistry. It is concluded that radiation-induced DNA damage production is greatly influenced by chromatin conformation, and that chromatin as it exists in the cell is a relatively poor substrate for DNA-protein crosslinking in comparison to completely expanded chromatin. PMID- 1734450 TI - Chronic exposure to ionizing radiation as a tumor promoter in mouse skin. AB - We have tested chronic exposure to 90Y beta radiation for its action as a complete tumor promoter, a stage I tumor promoter, or a stage II tumor promoter in SENCAR mouse skin. In skin initiated with a single application of 7,12,dimethylbenz[a]anthracene (DMBA, 10 nmol), chronic exposure to beta radiation as a complete promoter (0.5 Gy, twice/week, 13 weeks) produced no tumors and, when added to a complete chemical promoter (TPA), reduced tumor frequency about 30%. A similar result was observed when beta radiation was tested as a stage II promoter. DMBA-initiated mice that received chemical (12-O tetradecanoylphorbol-13-acetate, TPA) stage I promotion followed by 13 weeks of beta-radiation exposure (0.5 Gy, twice/week) as stage II promotion produced essentially no tumors, and combining the same chronic beta-radiation exposure with chemical (mezerein) stage II promotion reduced tumor frequency about 20% when compared to a similar group that was not irradiated. Chronic beta-radiation exposure was tested two ways as a stage I tumor promoter in initiated skin that was subsequently treated with mezerein as a stage II promoter. Stage I promotion was shown to proceed with the passage of time, indicating this process occurs naturally in the absence of chemical or physical stimulation. Hyperthermia, previously shown to be a potent inhibitor of chemically stimulated stage I promotion, had no effect on the natural process, indicating at least some differences in mechanism between the two processes. The natural process was, in fact, inhibited by chemical tumor promoters, but not by radiation. In addition to the increase resulting from this natural process, tumor frequency was further increased slightly but significantly (12-15%, P less than or equal to 0.05) when chronic radiation exposure was given as a stage I promoter (0.5 Gy, twice/week, 13 weeks) subsequent to initiation, in spite of the expected 20% reduction resulting from this dose. Exposure of initiated animals to radiation (0.5 or 1.0 Gy, twice/week, 2 weeks) in addition to TPA as stage I promotion produced a similar increase in tumor frequency (P less than 0.02). At higher radiation doses, however, tumor frequency was reduced compared to unirradiated controls. In a third test as a stage I promoter, beta radiation (0.5 Gy twice/week, 4 weeks) was given prior to initiation with N-methyl-N'-nitro-N-nitrosoguanidine in animals subsequently promoted by TPA (twice/week, 13 weeks), and again the radiation slightly but significantly (P less than 0.03) increased tumor frequency compared to the unirradiated control group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1734451 TI - Mechanism of radiosensitization by halogenated pyrimidines: effect of BrdU on repair of DNA breaks, interphase chromatin breaks, and potentially lethal damage in plateau-phase CHO cells. AB - There is evidence suggesting that radiosensitization induced in mammalian cells by substitution in the DNA of thymidine with BrdU has a component that relies on inhibition of repair and/or fixation of radiation damage. Here, experiments designed to study the mechanism of this phenomenon are described. The effect of BrdU incorporation into DNA was studied on cellular repair capability, rejoining of interphase chromosome breaks, as well as induction and rejoining of DNA double and single-stranded breaks (DSBs and SSBs) in plateau-phase CHO cells exposed to X rays. Repair of potentially lethal damage (PLD), as measured by delayed plating of plateau-phase cells, was used to assay cellular repair capacity. Rejoining of interphase chromosome breaks was assayed by means of premature chromosome condensation (PCC); induction and rejoining of DNA DSBs were assayed by pulsed field gel electrophoresis and induction and rejoining of DNA SSBs by DNA unwinding. A decrease was observed in the rate of repair of PLD in cells grown in the presence of BrdU, the magnitude of which depended upon the degree of thymidine replacement. The relative increase in survival caused by PLD repair was larger in cells substituted with BrdU and led to a partial loss of the radiosensitizing effect compared to cells tested immediately after irradiation. A decrease was also observed in the rate of rejoining of interphase chromosome breaks as well as in the rate of rejoining of the slow component of DNA DSBs in cells substituted with BrdU. The time constants measured for the rejoining of the slow component of DNA DSBs and of interphase chromosome breaks were similar both in the presence and in the absence of BrdU, suggesting a correlation between this subset of DNA lesions and interphase chromosome breaks. It is proposed that a larger proportion of radiation-induced potentially lethal lesions becomes lethal in cells grown in the presence of BrdU. Potentially lethal lesions are fixed via interaction with processes associated with cell cycle progression in cells plated immediately after irradiation, but can be partly repaired in cells kept in the plateau-phase. It is hypothesized that fixation of PLD is caused by alterations in chromatin conformation that occur during normal progression of cells throughout the cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1734452 TI - Neutron RBE for primate spinal cord treated with clinical regimens. AB - The RBEs of high-energy neutrons given in 9 or 12 fractions for cervical spinal cord injury in rhesus monkeys was determined using photons at 2.2 Gy per fraction as the reference radiation. Because the dose-response functions were not parallel, the RBE was not constant but rather increased with dose or, equivalently, with the probability of myelopathy. This required the development of a novel method of determining the RBE versus level of response. The RBE is presented as a function of probability of myelopathy from 0.1 to 99%. At a 50% incidence of myelopathy, the RBE (+/- 1 SE) was 5.22 +/- 0.15. A difference in the histopathology of lesions induced by photon and neutron treatments was observed. PMID- 1734453 TI - Hyperthermia-induced enhancement of melphalan activity against a melphalan resistant human rhabdomyosarcoma xenograft. AB - The effects of regional hyperthermia (42 degrees C for 70 min) on the antitumor activity of melphalan were examined in athymic mice bearing melphalan-resistant human rhabdomyosarcoma (TE-671 MR) xenografts growing in the right hind limb, and results were compared with similar studies of melphalan-sensitive (TE-671) parent xenografts. Melphalan alone at a dose of 36 mg/m2 (0.5 of the 10% lethal dose) produced growth delays of 4.1 to 10.2 days in TE-671 MR xenografts and 21.8 to 28.7 days in TE-671, respectively. Hyperthermia alone produced growth delays of 0.9 days in TE-671 MR xenografts and 0.8 days in TE-671. Combination therapy with melphalan and hyperthermia produced growth delays of 7.2 to 13.3 days in TE-671 MR xenografts and 34.3 to 42.8 days in TE-671, respectively, representing a mean thermal enhancement ratio of 1.7 in TE-671 MR and 1.5 in TE-671. Measurement of glutathione levels in TE-671 MR xenografts following treatment with melphalan, hyperthermia, or melphalan plus hyperthermia revealed significant reductions in glutathione content with the nadir (60% of control values) seen 6 h following treatment. Glutathione levels in TE-671 xenografts following identical therapy revealed no differences from control values. Hyperthermia plus melphalan did not result in a higher tumor-to-plasma melphalan ratio compared with treatment with melphalan alone in either TE-671 MR or TE-671 xenografts. These studies suggest that heat-induced alterations in tumor glutathione or melphalan levels are not responsible for the increase in melphalan activity produced by hyperthermia. Combination therapy with melphalan plus regional hyperthermia offers promise for treatment of melphalan-resistant neoplasms. PMID- 1734454 TI - Reduction of radiation-induced G2 arrest by caffeine. AB - A large number of studies have been undertaken in an attempt to define the mechanism by which caffeine (1,3,7-trimethylxanthine) reduces the duration of radiation-induced arrest of cells in the G2 phase of the cell cycle. These studies are summarized and those agents which mimic the action of caffeine are listed in the order of their potency. This ranking does not match any activities of these agents described previously, but provides a comparison for future studies, which might profitably include measurement of the ability of these agents to inhibit protein kinases. PMID- 1734455 TI - Contributions of the direct and indirect effects of ionizing radiation to reproductive cell death. PMID- 1734456 TI - Laser alignment system for high-quality portable radiography. AB - In portable radiography, image quality is degraded by scattered radiation. Use of an accurately aligned, antiscatter grid can provide consistently high image quality, but the necessary precision for grid alignment is difficult to achieve with conventional techniques. The authors developed a simple laser alignment method for bedside radiography. A compact laser device is mounted on the collimator housing of a mobile radiography machine, so that the laser beam is precisely parallel to the central x-ray beam. A small reflector device, which attaches to the edge of the grid cassette, indicates beam centering and alignment in a clear, intuitive way. In clinical use, the laser alignment technique provided uniformly high image quality, equivalent to that of fixed equipment. The system has the advantages of being simple to use and inexpensive to implement with existing equipment. PMID- 1734457 TI - The videodisc in medical education. PMID- 1734458 TI - Picture archiving and communication systems: an overview. AB - Organizational techniques that enable small departments to function efficiently often fail as departments become larger. With the recent growth in imaging technology, the capacity of film-based systems to meet the increasing needs of radiology departments has decreased. Electronic picture archiving and communication systems (PACS) have been developed in an attempt to provide economical storage, rapid retrieval of images, access to images acquired with multiple modalities, and simultaneous access at multiple sites. Input to a PACS may come from digital or analog sources (when the latter have been digitized). A PACS consists primarily of an image acquisition device (an electronic gateway to the system), data management system (a specialized computer system that controls the flow of information on the network), image storage devices (both short- and long-term archives), transmission network (which serves local or wide areas), display stations (which include a computer, text monitor, image monitors, and a user interface), and devices to produce hard-copy images (currently, a multiformat or laser camera). The goals of PACS are to improve operational efficiency while maintaining or improving diagnostic ability. PMID- 1734459 TI - Three methods of implementing a picture archiving and communication system. AB - A picture archiving and communication system (PACS) is a system integration of many components, including radiologic image acquisition devices, computers, communication networks, image display workstations, and data base management systems. The author describes three general approaches to implementing a PACS. In the first approach, the department or institution acts as a systems integrator, designing and implementing the PACS. In the second approach, the PACS is planned on the basis of the department's operations and environment and then a manufacturer is contracted to design and build the system. The third approach is to purchase a turnkey system, with some modifications provided by the manufacturer for a specific clinical application. The author provides examples of each approach in the clinical environment and presents the disadvantages and advantages of each. PMID- 1734460 TI - Evaluation of requirements and planning for picture archiving and communication systems. AB - Successful implementation of a picture archiving and communication system (PACS) requires extensive planning and the input of the users in the planning and evaluation stages. System design is conducted in nine stages: systems analysis, stages 1-4; system design, stages 5 and 6; and system implementation, stages 7-9. Users of the PACS are actively involved in systems analysis. At stage 1, problems are identified, project scope is defined, and whether the problems can be successfully addressed with a PACS is determined. If the project is feasible, current systems are studied at stage 2. Data are collected on the volume of image data to be transmitted, stored, retrieved, and displayed; distribution of imaging through the day; radiologists' reading patterns and volumes; job functions of technologists; characteristics of images to be included; types of equipment to be interfaced; physical placement of cables, connections, and equipment; and operational restrictions. All these data and more are used in stage 3 to specify requirements of the PACS. Rigorous specifications are needed to ensure that the final system performs at the desired level. At stage 4, users evaluate alternative solutions to problems. Although consultants and equipment manufacturers do much of the design, implementation, and installation, users must understand project scope and limitations of the technology and must ultimately be responsible for planning a system that meets their needs. PMID- 1734461 TI - Thymoma: radiologic-pathologic correlation. AB - Thymoma is the most common primary neoplasm of the thymus. The majority of thymomas are encapsulated masses and exhibit a benign behavior. Less frequently, thymomas may be locally invasive, or rarely they may metastasize to distant sites. The usual clinical presentation is that of an anterior mediastinal mass found incidentally in an asymptomatic patient. The variable gross features of thymoma and the potential for local invasion result in a variety of radiologic appearances. The most common radiologic manifestation is a rounded, soft-tissue mass of the anterior superior mediastinum. Computed tomography and magnetic resonance imaging typically show a prevascular mediastinal mass of variable size and may be helpful in the evaluation of adjacent structures in cases of invasive thymoma. The treatment of choice is complete surgical excision. Radiation therapy and chemotherapy may be used adjunctively to surgery in the treatment of invasive tumors. The prognosis of encapsulated thymoma is generally favorable. Invasive tumors are associated with a worse prognosis but may respond to radical resection. PMID- 1734462 TI - Image interpretation session. Primary carcinoma of the male breast with lymphangitic spread to the lungs. PMID- 1734463 TI - Image interpretation session. Multiple benign pheochromocytomas. PMID- 1734465 TI - Image interpretation session. Mycetoma of the right foot. PMID- 1734464 TI - Image interpretation session. Gonadotropin insufficiency secondary to pituitary siderosis in a patient with thalassemia major and repeated blood transfusions. PMID- 1734466 TI - Image interpretation session. Cystic fibrosis with distal intestinal obstruction syndrome or meconium ileus equivalent. PMID- 1734468 TI - Image interpretation session. Focal xanthogranulomatous pyelonephritis. PMID- 1734467 TI - Image interpretation session. Mediastinal parathyroid adenoma with hyperparathyroidism. PMID- 1734469 TI - Image interpretation session. Rhinocerebral mucormycosis. PMID- 1734470 TI - Image interpretation session. Tuberculosis dactylitis, psoas abscess, and lumbar vertebral tuberculosis osteomyelitis. PMID- 1734471 TI - Image interpretation session. Ischemic small bowel, arterial embolus, and left atrial myxoma. PMID- 1734472 TI - Pediatric case of the day. Right ovarian torsion, amputation, and calcification. PMID- 1734473 TI - Proper terminology for the left periaortic area. PMID- 1734474 TI - Ultrasound case of the day. Right adnexal torsion. PMID- 1734475 TI - General case of the day. Cystic rheumatoid arthritis. PMID- 1734476 TI - Communicating risk information in medical practice. AB - The public's preceptions about the risks of radiation are adversely influenced by the many negative reports by the media on the hazards of all radiation. As a result, patients express concern about the risks of radiation from radiologic examinations. Radiologists are well positioned to dispel these fears because of their training and their access to and ability to interpret information from scientific organizations specifically concerned with the determination of radiation risk. To do this, radiologists must be willing to communicate with patients and be accessible. Pamphlets and handouts can be given to anxious patients before examinations. In direct interaction with patients, the radiologist must listen to them and be prepared to address their concerns, especially those about repeat examinations, exposure during pregnancy, inadvertent exposure of the fetus, exposure of children, use of radiation in research, and misadministration of radionuclides. In addition, radiologists can help patients by educating referring physicians, other medical staff, and nurses. They can also reach the public by being a spokesperson at meetings of local organizations or by accepting opportunities to speak to the media. All these efforts help counteract negative perceptions aroused by the media. PMID- 1734477 TI - Gd-DOTA-enhanced MR imaging and color Doppler US of renal allograft necrosis. AB - In 21 recipients of renal transplants suspected of allograft necrosis, the authors correlated the results of imaging to pathologic and histologic data in order to describe the magnetic resonance (MR) imaging and color Doppler ultrasonographic (US) characteristics of infarction. All patients underwent MR imaging performed with and without gadolinium tetraazacyclododecanetetraacetic acid (DOTA) and color Doppler US. Nonenhanced T1-weighted images showed no obvious changes, whereas nonenhanced T2-weighted images demonstrated a slight increase in signal intensity in areas of ischemic necrosis and low or heterogeneous signal intensity in areas of hemorrhagic necrosis. Gd-DOTA-enhanced MR images showed no contrast material uptake in infarcted areas. Color Doppler US characteristics of infarction included absence of Doppler signal and alteration of the cortical echogenic structure, particularly in cases of ischemic necrosis. Color Doppler US allows measurement of vascular resistance and assessment of intrarenal vasculature and the renal pedicle. Gd-DOTA-enhanced MR imaging is useful in confirming the diagnosis of infarction and provides an accurate evaluation of the extent of the infarct. PMID- 1734478 TI - Color Doppler sonography in the evaluation of erectile dysfunction. AB - Color Doppler sonography can be useful in the evaluation of erectile dysfunction, which can result from psychogenic, endocrinologic, neurogenic, pharmacologic, and vasogenic causes. It is used to determine the integrity of the vascular mechanism. After an intracavernosal injection of a vasodilatory agent, color Doppler sonography is performed to evaluate cavernosal arteries and dorsal vessels. Color flow imaging allows direct visualization of intrapenile anatomy, vascular variants, and disease. It is also helpful in demonstrating transitions in cavernosal and dorsal blood flow. Color Doppler sonography is combined with spectral interrogation of the cavernosal arteries and dorsal veins to help determine peak systolic and end-diastolic velocities. Cavernosal artery size and systolic velocities help diagnose arterial insufficiency. Recent work on cavernosal artery diastolic flow and dorsal vein flow has indicated that color Doppler sonography, when correlated with cavernosographic findings, may be helpful in diagnosing venous incompetence. Temporal variations in transitions in cavernosal artery and dorsal vein flow during various stages of erection are important in the accurate diagnosis of vasogenic impotence. PMID- 1734479 TI - Sexual harassment in radiology departments. PMID- 1734480 TI - Spectral and color Doppler artifacts. AB - Artifacts in spectral and color Doppler imaging can be confusing and lead to misinterpretation of flow information. The authors review these artifacts by considering three main causes: inappropriate equipment settings, anatomic factors, and physical and technical limitations of the modality. Incorrect gain, wall-filter, or velocity scale settings can cause loss of clinically important information or distortion of the tracing. Reflection of the Doppler signal from highly reflective surfaces can create a color Doppler mirror image. Vascular motion can introduce artifactual variation in velocity as the sample volume passes through different velocities in a laminar flow state. Unintentional motion can cause a generalized Doppler shift. Increasing the angle of Doppler interrogation degrades the quality of the tracing and gives the impression of spectral broadening. As angulation approaches 90 degrees, directional ambiguity can occur, suggesting bidirectional flow. Grating and side lobes can interrogate areas unrelated to the sample volume and introduce extraneous Doppler information to the apparent area of interrogation. Recognition of these artifacts is essential to proper interpretation of Doppler information and rendering a correct diagnosis. PMID- 1734481 TI - High-resolution CT of parenchymal lung disease: precise correlation with histologic findings. AB - To provide a precise correlation between high-resolution computed tomographic (CT) findings and histologic studies of various parenchymal lung diseases, 20 fixed and inflated lungs were studied as follows: (a) Every lung was cut at the corresponding CT level into 1.5-mm-thick sections, (b) selected slices were cut into small blocks to prepare histologic slides, (c) each slide was photographed, and (d) the image of the entire lung section was reconstituted with the enlarged photographs (assembled as in a jigsaw puzzle). Results obtained in cases of normal lungs, pulmonary edema, alveolitis, hypersensitivity pneumonitis, emphysema, Pneumocystis carinii pneumonia, silicosis-asbestosis, and idiopathic pulmonary fibrosis demonstrated the method to be accurate in correlating high resolution CT findings and the corresponding histologic data. PMID- 1734482 TI - Appendices epiploicae of the colon: radiologic and pathologic features. AB - Appendices epiploicae are adipose structures protruding from the serosal surface of the colon. They can be seen with abdominal radiography and cross-sectional imaging if the colonic wall is surrounded by intraperitoneal contrast material, ascites, or blood. Normal appendices epiploicae appear as lobulated masses of pericolic fat, usually 2-5 cm long and 1-2 cm thick. Their enlargement, deformity, or altered radiopacity may result from various pathologic processes that can originate locally or extend from adjacent viscera. In a series of 22 cases, appendices epiploicae were affected by spontaneous torsion and hemorrhagic infarct, calcification due to aseptic fat necrosis, primary or secondary inflammation, enlargement by lipomas or metastases, and incarceration in hernias. Disorders of appendices epiploicae are often manifested by nonspecific clinical signs and symptoms (eg, torsion is often mistaken for appendicitis or diverticulitis). These entities should be included in the differential diagnosis of any unexplained abdominal pain or pericolic lesions in adults. PMID- 1734483 TI - Radiographic caricature as a medical illustration. PMID- 1734484 TI - US-guided percutaneous pancreatography: an essential tool for imaging pancreatitis. AB - The pancreatic duct can be opacified when contrast material is injected through a fine needle percutaneously placed under ultrasound (US) guidance. Percutaneous pancreatography was performed in 63 patients with chronic pancreatitis diagnosed at US or computed tomography (CT). In 52 of these patients, endoscopic retrograde pancreatography (ERP) was unsuccessful or did not enable complete visualization of the duct. The percutaneous pancreatograms and other relevant images of these patients were retrospectively reviewed. Percutaneous pancreatography was successful in 54 patients (86%), in whom it clearly mapped the full ductal anatomy, depicted the relationship between cavities seen at US or CT and the duct, and allowed assessment of duct drainage after antegrade injection of contrast material. This information was not provided by other modalities. Percutaneous pancreatography is a valuable complement to CT, US, and ERP for imaging chronic pancreatitis. PMID- 1734485 TI - MR imaging in high-risk obstetric patients: a valuable complement to US. AB - The accuracy of prenatal diagnosis has become increasingly critical in the field of high-risk obstetrics. Although ultrasound (US) provides adequate information in most cases and continues to be the initial prenatal examination of choice, there are instances in which the results of the US study may be equivocal. The role of magnetic resonance (MR) imaging was explored in 27 selected patients with various indications to determine its effectiveness as a complement to US. MR imaging was most helpful in the diagnosis of extrauterine gestation, evaluation of placental position, determination of extent or nature of masses associated with pregnancy, and differentiation between diaphragmatic hernia and a thoracic mass. Although MR imaging did not add information that affected the accuracy of the diagnosis of oligohydramnios, in all other cases it provided an extra dimension in diagnosis by showing clearer anatomic relationships in the pelvis. It has proved to be a valuable complement to an equivocal US study. PMID- 1734486 TI - [Blood pressure measurement using the fingers]. AB - An increasing number of devices for self-assessment of blood pressure has been developed over the past years. Accepted international standards for evaluation of such devices are still lacking. A new apparatus (T88, Marshall Electronics) measuring blood pressure on digital arteries by oscillometry was tested for accuracy. Comparative measurements in 36 patients indicated position-dependent results with a reasonable correlation with the measurements taken on the upper arm only if the device was used at the level of the heart. Significant differences for systolic values were noted on different phalanges. In a last series of measurements, comparing values obtained about the basal phalanges of the index positioned at the level of the heart, significant differences were found for systolic and diastolic values compared to the traditional measurement. The use of this device for evaluation of hypertension, monitoring of treatment or use in studies is thus not recommended. PMID- 1734487 TI - [Self measurement of blood pressure: automation and management problems]. AB - In the Federal Republic of Germany, the introduction of clinical testing of devices designed for the self-measurement of blood pressure resulted in an improvement of quality of these devices during the last ten years. Further progress seems to be possible by more restrictive administrative prescriptions. Now, electronic devices have the same accuracy as stethoscope devices. They facilitate self-measurement especially in handicapped persons. Devices working by the oscillometric method do not measure blood pressure more accurately than Korotkow devices, but they are a bit less sensitive for wrong placing of the bladder. In most devices automation of the prescribed deflation rate (2 to 3 mmHg/s) was successful. PMID- 1734488 TI - [Self measurement of blood pressure: normal and pathological values]. AB - To date, the normal range for self-recorded blood-pressure values has yet to be defined. In this paper possible definitions of the normal range of self-recorded blood pressure are discussed. In large epidemiologic studies self-recorded and casual blood-pressure values should be compared to each other, and in prospective interventional studies blood-pressure values for the initiation of therapy should be defined. Before the termination of these studies we recommend the start of an antihypertensive therapy above 140/90 mmHg. Although definite normal values for self-recorded blood pressure are still missing, a broader use of this method seems to be justified because of the well-known pitfalls of the causal clinical blood-pressure measurement. PMID- 1734489 TI - [Technique and interpretation of 24-hour blood pressure measurements]. AB - Development of ambulatory repetitive recording of blood pressure during day and night under normal daily activity demonstrates a marked fall in blood pressure of normo- and hypertensive individuals during the night hours. Although no general consensus exists on normal values for such measurements, the upper normal limit appears to be 140/90 mmHg during the day and 120/80 mmHg during the night. This method also avoids the excessive rise in blood pressure induced by the physician (white-coat effect). Furthermore, it permits an exact assessment of efficacy of antihypertensive treatment. It may also provide means for better characterization of hypertension as risk factor in general, although there is still a lack of experience to estimate its cardio-vascular risk potency. PMID- 1734490 TI - [What is your diagnosis? Carbon monoxide poisoning--attempted suicide]. PMID- 1734491 TI - [Are mercury sphygmomanometers obsolete?]. AB - The measurement of blood pressure during medical visits is limited in its diagnostic, prognostic and therapeutic value by physiologic variability of hypertension and measurement errors. Repeated measurements reduce the effect of spontaneous variations of blood pressure. They allow a more secure assessment of real tension. Regular training for proper technique and elimination of arbitrary preference for rounded last digits or automated recording minimize erroneous measurements. By the multitude of recorded parameters the ambulatory measurement over 24 hours and the self-assessment of blood pressure provide a representative diurnal profile superior to individual measurements at the doctors office. Each of the two methods has its own field of application, although prognostic and therapeutic aims seem similar. The continuous recording over 24 hours is suited for initial assessment and identification of hypertensive patients. Self assessment of blood pressure has its use for long-term follow up and optimization of therapy. Both methods are complementary and only limited from wider use by lacking internationally accepted normal values and standardization of available devices. PMID- 1734492 TI - The Nobel lectures in immunology. The Nobel Prize for Physiology or Medicine, 1977 awarded to Rosalyn S. Yalow. PMID- 1734493 TI - T-independent polyclonal activation of B cells in vitro by immunoglobulin binding substance (IBS) from the granary weevil. AB - Experiments are described for T-independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity-chromatographically purified IBS was used. IBS is a heat-, alkali- and acid-stable glucopeptide which is characterized by non-specific immunoglobulin binding to the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12-14,000, 25-30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages. IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and experimentally. PMID- 1734494 TI - Production of heterohybridomas secreting autoreactive and polyreactive human monoclonal antibodies. AB - Peripheral blood lymphocytes from two polytransfused renal dialysis patients were transformed by Epstein-Barr virus, fused to a heteromyeloma and cloned. Eight human monoclonal antibodies from the resulting clones were tested for their binding to a variety of antigens by ELISA, indirect immunofluorescence and immunoblotting. Antigens tested included B-cell lines, T and B lymphocytes, red blood cells, chronic lymphocytic leukaemic B cells, IgG, ssDNA, dsDNA, histones, nucleoprotamine, sperm nuclei, thymus and spleen extracts, MOLT4 cell lysates, affinity purified autoantigens, tetanus toxoid, bacterial lipopolysaccharide, insulin, and a tissue section screen. These human monoclonal antibodies reacted with more than one antigen to varying degrees and were autoreactive and polyreactive. One of these heterohybridoma cell lines exhibited cytoplasmic staining with an anti-CD5 monoclonal. Our findings support the concept that in adult individuals a subset of B cells produce heterogeneous IgM antibodies which can bind to a variety of different autoantigens and also to foreign antigens. These monoclonals were different from the autoantibodies usually seen in renal dialysis patients in the sense that they were not lymphocytotoxic. PMID- 1734495 TI - Clustering of IgA-producing immunocytes related to HLA-DR-positive ducts in normal and inflamed salivary glands. AB - Ig-producing immunocytes and epithelial expression of secretory component (SC) and HLA-DR were evaluated by two-colour immunofluorescence staining in 10 normal and 20 inflamed salivary glands; the latter included specimens from 10 patients with obstructive sialadenitis and 10 with Sjogren's syndrome (SS). Epithelium adjacent to T-cell infiltrates showed extensive co-expression of SC and HLA-DR, suggesting that leucocyte-derived cytokines were responsible for this concurrent up-regulation. Clusters (greater than 2 positive cells) of IgA-producing cells were spatially related to DR-positive ducts. The possibility is discussed that DR expressing epithelium contributes to local terminal differentiation of IgA producing plasma cells. A cytokine-mediated up-regulation of SC that simultaneously increases the transport capacity for polymeric IgA would constitute an efficient enhancement of secretory immunity in diseased glandular tissue. PMID- 1734496 TI - Regulation of the immune response to hepatitis B virus and human serum albumin. III. Induction of anti-albumin antibody secretion in vitro by C-gene-derived proteins in peripheral B cells from chronic carriers of HBsAg. AB - The circulatory pool of B cells from the majority (11/13) of chronic hepatitis B surface antigen (HBsAg) carriers contained sensitized B cells with the capacity to secrete IgG antibodies with specificity for human serum albumin (HSA), when stimulated with E. coli-derived core protein at low concentrations in vitro. The IgG anti-HSA secretion was dependent upon and regulated by T cells, and optimal secretion was obtained at T/B-cell ratios of 1.0-4.0, varying for different individuals. The level of anti-HSA secretion was higher for patients with on going viral replication as assessed by hepatitis B virus (HBV)-DNA in serum. Culture supernatants containing anti-HSA antibodies also contained anti-HBc antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) where the solid phase was charged with E. coli-derived core protein, or the synthetic peptides corresponding to the 75-84 and 132-147 sequences in the C region of HBV. In contrast, IgG anti-HBc (E. coli-derived), but no anti-HSA or anti-HBc 75-84, 132-147 antibodies, were detected at similar T/B-cell ratios in cell cultures from 5/6 individuals with naturally acquired immunity to hepatitis B. These data indicate that peripheral B cells from the majority of HB-immune donors are sensitized to unique (e.g. non-albumin associated) structures in the nucleocapsid of HBV, while B cells in the majority of chronic HBsAg carriers are sensitized to linear C-gene-derived structures in association with the host 'self'-component HSA. PMID- 1734497 TI - Amino acid sequence analyses of non-AA proteins from amyloid fibrils of bovine kidney. AB - The elution pattern obtained when amyloid fibrils from amyloid-laden bovine kidneys were subjected to gel filtration under dissociating conditions revealed a larger amount of non-AA material (eluting between the void volume and protein AA) than usually seen in other species. SDS-PAGE of this non-AA fraction yielded several Coomassie blue stained bands. The most distinctive ones gave estimated molecular masses of 15 kDa, 18 kDa, 33 kDa and 43 kDa. These molecular species were electroblotted onto PVDF membranes, and were further characterized by amino acid composition analyses, cyanogen bromide cleavage and N-terminal analyses. The results revealed that the intermediate 'non-AA' fraction consisted of histones H2B, H3 and H4 in addition to protein AA also found in this fraction. PMID- 1734498 TI - Secretory component is bound to the paraproteins in sera of IgA and IgM gammopathies. AB - Secretory immunoglobulins A (SIgA) and M (SIgM) were investigated in 20 sera containing high levels of monoclonal polymeric IgM or IgA. In the sera of patients suffering from Waldenstrom's macroglobulinemia (WM), the level of SIgA was found to be low, whereas that of SIgM was extremely high. Reciprocally, in the multiple myeloma (MM) patients, SIgA were increased and SIgM were dramatically decreased. Electrophoretic analysis showed these SIgA and SIgM to have the same monoclonal pattern as the corresponding paraprotein. Hence these molecules must originate from the malignant clone. The most likely mechanism involved is an intravascular formation of the secretory-like immunoglobulins. Free secretory component (SC) could diffuse passively from the digestive lumen and bind the circulating myeloma polymeric immunoglobulins. Such a possibility of in vivo binding of free SC to IgM and IgA polymers leads to a reconsideration of the secretory origin of SIgM and SIgA in normal human serum. PMID- 1734499 TI - Generation of iC3 at the interface between blood and gas. AB - Earlier studies have shown that C3 can be denatured when blood comes in contact with a polystyrene surface. This study was undertaken to see if similar denaturation of C3 occurs at the gas-plasma interface which is found in all kinds of oxygenator used during cardio-pulmonary operations. An in vitro system consisting of gas bubbling through human blood, serum or plasma was used. The generation of C3a, as an indicator of complement activation, and iC3 and iC3 fragments were monitored. Both C3a and iC3/iC3 fragments levels were increased during bubbling. In contrast to the C3a level, no reduction in iC3/iC3 fragments formation was seen in the presence of EDTA, indicating that it was independent of complement activation. The rate of iC3/iC3 fragments generation was unaffected by the composition of the gas (pure oxygen, pure nitrogen or air), suggesting that the denaturation of C3 indeed occurred at the serum-gas interface. C3 and iC3/iC3 fragments were isolated from bubbled EDTA-chelated serum by PEG precipitation and chromatography on FPLC, using a Mono S column and detected by two ELISAs, specific for native C3 and iC3/iC3 fragments. After 240 min approximately 20% of the total amount of C3 consisted of intact iC3 and it was confirmed that this population bound to human erythrocytes. PMID- 1734500 TI - [Mild and severe organic brain disorders in childhood]. AB - An outline of the classification of minor brain dysfunction and severe brain syndrome is followed by a short historical sketch of the development of the concept of minor brain dysfunction and a description of the clinical and diagnostic relevance of this concept. After evaluation of specific therapeutic approaches, selected empirical studies are reported to elucidate the course of the disorder. The issue concerning the existence of a behavioral syndrome that characterizes severe brain disorders is discussed. The presentation of selected research findings on psychopathological and neuropsychological sequelae of severe brain traumas provides the argument for the final discussion. The necessity of qualifying a highly specific, narrowly defined psychopathological syndrome in childhood is emphasized. PMID- 1734501 TI - [Role of the parents with the chronically ill child]. AB - The term "chronic illness" subsumes a multitude of conditions and complaints, all of varying development. It is often impossible to establish a prognosis and only seldom is causal therapy available. A chronic illness or handicap must be seen as fate, not only for the affected child but also for his or her family. Both require concerned and competent support towards mastering their situation in a justifiably realistic way. A highly developed network must be available to families of chronically ill children to help them prevent and overcome crisis. The organization of this network requires much planning and effort. In many families with chronically ill or handicapped children the ability to develop and to make decisions can only be regained when the hopelessness and helplessness involved in having a severely chronically ill child has been recognized and accepted by all concerned. PMID- 1734502 TI - [Psychosocial aspects of cystic fibrosis]. AB - Psychosocial stress and coping in families with cystic fibrosis (CF) are described. The illness does not lead to specific psychopathological disturbances, but with additional intra- or extra-familial stress, patients and family members are more vulnerable to psychoreactive disorders. Interdisciplinary and family oriented bio-psycho-social care is required. The role of the child psychiatrist is discussed. PMID- 1734503 TI - [Psychosomatic aspects of growth retardation]. AB - Emotional deprivation is one of the possible causes of failure to thrive. Deprivation dwarfism is also associated with growth hormone deficiency, which disappears when the child is removed from his harmful environment. This phenomenon may constitute a pertinent model for etiopathogenic studies in child psychosomatics with particular emphasis on exploration of the linkage between biological, environmental and psychic factors. PMID- 1734504 TI - [The adolescent with a chronic somatic disorder]. AB - Adolescence, a period of psychic reorganization which allows for new adjustments in order to face future life and reorganize the experience of the past, is one of the critical phases of existence. It is described as a "new birth", a successful achievement of individuation and separation processes. For the adolescent with an infirmity or chronic illness, and for his family, there exist specific problems in addition to those encountered by a healthy adolescent. The painful realization of social, professional and relational barriers is reactivated. The feeling of failure and helplessness, the impairment of self-esteem, and anger at being the victim of the unfairness of destiny, represent a supplementary affective burden for the adolescent and his family. This results in a risk of deterioration, either towards affective and social withdrawal expressed by overadaptation and weakening of psychic functions, or towards autoaggressive acting-out or various forms of marginalization. Preventive and therapeutic action by the individual and the family are discussed in the light of the case history of an adolescent suffering from a facial malformation. PMID- 1734505 TI - [The role of liaison psychiatry in the framework of chronic disease]. AB - Liaison psychiatry in paediatrics should not be confined to psychiatric cases. Due to their special skills, psychiatrists can be helpful in the long term care of chronically ill children. The case of cystic fibrosis is cited to show how this disease affects the family; how educating patients (and their parents) about the disease and treatments is essential; how compliance is affected by factors such as family characteristics and psychological characteristics of young patients. Poor compliance is seen as a symptom that can, to a certain extent, be treated by psychological analysis of all the factors involved. PMID- 1734506 TI - [Chronic disease and adolescence]. AB - Chronic disease is not a strictly defined term and includes a large number of illnesses ranging from physical to mental impairment. It is estimated that between 10% and 20% of adolescents have a chronic disease. Independence and new relations, acceptance of a new body image and sexuality, career plans and cognitive maturation are core topics in development to adulthood. Chronic disease may interfere with these developmental tasks. Most often there is no specific psychopathology, but the type of impairment, its influence on family life and functioning, age at onset, gender, and other factors will interact with psychosocial maturation. Because of the important role of the family, not only the adolescent patient him/herself, but also parents and siblings need to be included in all major decisions. As hospitalizations may be disruptive they must be planned, taking in account the patient's plans and opinions. Chronic disease may lead to death during the period of adolescence. It is believed that the concept of one's own mortality develops at age 14 to 17 years, a fact that will influence care during the terminal stage of a disease. Whatever the problems and questions raised by the family, the developmental stage of the adolescent has always to be considered when dealing with specific issues of chronic disease. Periodic reassessment of psychosocial development is therefore one of the main tasks of the primary care physician. Counselling will address not only the disease but also the developmental tasks of any teenager. PMID- 1734507 TI - [The therapeutic challenge of anorexia nervosa]. AB - Anorexia nervosa represents a typical paradox of adolescence. This paradox drives the adolescent to refuse what he fears he would need too much: this need seems threatening because it would make him dependent on the object of satisfaction which seems alienating to him. Thus, he becomes alienated to his refusal, which worsens the underlying need and increases the refusal. The life of the anorectic is centered on a passion for food and fear of bulimia. In fact, food focuses a greater "appetite" for recognition and to be the centre of attention. Beyond, and with, curing of the symptom, the treatment, by means of the weight contract, tends to resolve this paradox in which the anorectic tries to enclose us. To take up the challenge, the treatment must create the conditions for the emergence of pleasure in desiring what they need, without anxiety about their autonomy. PMID- 1734508 TI - Growing strong. Biotechnology's new wave hopes that being first will pay off. PMID- 1734509 TI - Under construction. Temporary scaffolding guides nerves in the developing brain. PMID- 1734510 TI - Turing test. A computerized therapist for human passes (almost) PMID- 1734511 TI - Inside job. Antibodies can destroy some viruses inside neurons. PMID- 1734512 TI - Profile: David Baltimore. A troubled homecoming. PMID- 1734513 TI - How cells absorb glucose. PMID- 1734514 TI - Air pollution and mortality. PMID- 1734516 TI - Coping with an "embarrassment of riches". PMID- 1734515 TI - The case of the Florida dentist. PMID- 1734517 TI - Stanford and MIT in the dock? PMID- 1734518 TI - Information processing in the primate visual system: an integrated systems perspective. AB - The primate visual system contains dozens of distinct areas in the cerebral cortex and several major subcortical structures. These subdivisions are extensively interconnected in a distributed hierarchical network that contains several intertwined processing streams. A number of strategies are used for efficient information processing within this hierarchy. These include linear and nonlinear filtering, passage through information bottlenecks, and coordinated use of multiple types of information. In addition, dynamic regulation of information flow within and between visual areas may provide the computational flexibility needed for the visual system to perform a broad spectrum of tasks accurately and at high resolution. PMID- 1734519 TI - Addictive drugs: the cigarette experience. AB - Cigarettes are among the most addictive substances of abuse and by far the most deadly. In this country smokers know it and try to stop. Their success has been dramatic but partial and excruciatingly slow, and until recently quite uncoerced by government. Cigarettes and nicotine have characteristics distinct among addictive drugs, and some of these help explain why efforts to quit smoking are so often frustrated. Nicotine itself is the most interesting chemical in the treatment of addiction and, in some forms, can pose a dilemma: compromise by settling for pure nicotine indefinitely, or stay with cigarettes and keep trying to quit. Nicotine is not alone among addictive drugs in becoming increasingly identified with the poorer classes. PMID- 1734520 TI - Widespread dispersion of neuronal clones across functional regions of the cerebral cortex. AB - The cerebral cortex of the mammalian brain has expanded rapidly during the course of evolution and acquired structurally distinguishable areas devoted to separate functions. In some brain regions, topographic restrictions to cell intermixing occur during embryonic development. As a means of examining experimentally whether such restrictions occur during formation of functional subdivisions in the rat neocortex, clonally related neocortical cells were marked by retroviral mediated transfer of a histochemical marker gene. Clonal boundaries were determined by infection of the developing brain with a library of genetically distinct viruses and amplification of single viral genomes by the polymerase chain reaction. Many clonally related neurons in the cerebral cortex became widely dispersed across functional areas of the cortex. Specification of cortical areas therefore occurs after neurogenesis. PMID- 1734521 TI - Sporogonic development of a malaria parasite in vitro. AB - The sporogonic cycle of the avian malaria parasite Plasmodium gallinaceum was completed in vitro. Ookinetes (motile zygotes) were seeded onto a murine basement membrane-like gel (Matrigel) in coculture with Drosophila melanogaster cells (Schneider's L2). Transformation into oocysts as well as subsequent growth and differentiation were observed in parasites attached to Matrigel and depended on the presence of L2 cells. Sporozoites were first observed on day 10 in culture. Specific circumsporozoite protein antigenicity was identified in mature oocysts and in sporozoites. It is now possible to follow the entire life cycle of Plasmodium in vitro. PMID- 1734522 TI - DNA binding activity of recombinant SRY from normal males and XY females. AB - The protein encoded by the human testis determining gene, SRY, contains a high mobility group (HMG) box related to that present in the T cell-specific, DNA binding protein TCF-1. Recombinant SRY protein was able to bind to the same core sequence AACAAAG recognized by TCF-1 in a sequence dependent manner. In five XY females point mutations were found in the region encoding the HMG box. In four cases DNA binding activity of mutant SRY protein was negligible; in the fifth case DNA binding was reduced. These results imply that the DNA binding activity of SRY is required for sex determination. PMID- 1734523 TI - GnRH-induced Ca2+ oscillations and rhythmic hyperpolarizations of pituitary gonadotropes. AB - Secretion of gonadotropic hormones from pituitary gonadotropes in response to gonadotropin-releasing hormone (GnRH) is essential for regulation of reproductive potential. Gonadotropes from male rats exhibited an unusual form of cellular excitation that resulted from periodic membrane hyperpolarization. GnRH induced an oscillatory release of intracellular Ca2+ via a guanosine triphosphate (GTP) binding protein-coupled phosphoinositide pathway and hyperpolarized the gonadotrope periodically by opening apamin-sensitive Ca(2+)-activated K+ (SK) channels. Each hyperpolarization was terminated by firing of a few action potentials that may result from removal of inactivation from voltage-gated Na+ and Ca2+ channels. PMID- 1734524 TI - Predicted structural similarities of the DNA binding domains of c-Myc and endonuclease Eco RI. AB - The c-Myc oncoprotein belongs to a family of proteins whose DNA binding domains contain a basic region-helix-loop-helix (bHLH) motif. Systematic mutagenesis of c Myc revealed that dimerized bHLH motifs formed a parallel four-helix bundle with the amino termini of helices 1 and 2 directed toward the inner and outer nucleotides of the DNA binding site, respectively. Both the basic region and the carboxyl-terminal end of the loop contributed to DNA binding specificity. The DNA binding domain of c-Myc may therefore be structurally similar to that of restriction endonuclease Eco RI. PMID- 1734525 TI - Aromatase enzyme activity and sex determination in chickens. AB - During development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens. PMID- 1734526 TI - Axon guidance by gradients of a target-derived component. AB - Spatial gradients of axon guiding molecules have long been suspected to provide positional and directional cues for retinal ganglion cell axons growing within the optic tectum. With the identification of a guiding activity from tectal cell membranes, it has become possible to investigate the potential physiological significance of molecular gradients for retinal growth cone behavior in vitro. A subset of retinal growth cones, those from the temporal half, were highly sensitive to small concentration changes of the guiding component. The degree of response was correlated with the strength of the gradient. These findings demonstrate that the neural growth cone can read gradients of surface-associated information. PMID- 1734527 TI - Oral ofloxacin therapy for lower respiratory tract infection. AB - We made an open, noncomparative evaluation of ofloxacin, 400 mg orally bid for 10 days, in 98 subjects with community-acquired pneumonia or pathogen-confirmed bronchitis. Thirty-nine (40%) of the subjects were treated in the hospital and 59 (60%) were treated as outpatients. The mean age of those treated was 56.2 years; 73 (74%) of the subjects either were more than 60 years old or had a history of chronic obstructive pulmonary disease, or both. There were 95 organisms initially isolated in sputum, aspirate, or lavage fluid; all were susceptible to ofloxacin, and none acquired resistance during therapy. Haemophilus influenzae was the most common pathogen (19 isolates), followed by Streptococcus pneumoniae (18) and Staphylococcus aureus (10). Clinical responses included cure in 70 patients (71%), improvement in 26 (27%), and failure in two (2%). After 10 days of therapy, pathogens persisted in two cases; in one case, Streptococcus salivarius was isolated, though it remained susceptible to ofloxacin, and in the other, Klebsiella pneumoniae was accompanied by superinfection due to a resistant strain of Serratia marcescens. We included in this study three confirmed cases of atypical pneumonia successfully treated with ofloxacin, two of them due to Mycoplasma pneumonia and one to Legionella pneumophila. Ofloxacin was well tolerated. Our data indicate that ofloxacin is effective and safe as specific and empiric treatment for many lower respiratory tract infections. PMID- 1734529 TI - Too smart for our own good. PMID- 1734528 TI - Appendicitis complicating pregnancy. AB - In this series, nine pregnant patients had appendectomy. Seven patients had acute appendicitis; pyuria and symptoms suggesting urinary tract infection delayed diagnosis in one whose appendix perforated. Abdominal pain and nausea with or without vomiting were presenting symptoms in all of the patients. Tenderness in the right lower quadrant was present in six. Eight patients, including two with a normal appendix, had leukocytosis with a left shift. There was no fetal or maternal loss. In addition, I reviewed more than 900 other cases of appendectomy during pregnancy, as reported in the literature since 1960. Among 713 previously reported cases of confirmed appendicitis, rupture had occurred in 25%. There were five maternal deaths, all in the group of patients with perforation. Perinatal mortality was 4.8% among patients with acute inflammation only and 19.4% in those with perforative appendicitis. The diagnosis rests on clinical acumen, and prompt surgical intervention is the key to good outcome. PMID- 1734530 TI - Effects of dietary stearic acid on plasma cholesterol levels. AB - Dietary advice based on saturated versus unsaturated fatty acids for the purpose of controlling the plasma cholesterol level has for many years plagued the American public with unpalatable diets that are difficult to adhere to. Stearic acid, an 18-carbon saturated fatty acid, does not share the hypercholesterolemic effect of other saturated fatty acids and may be the key to more palatable diets for the cholesterol-conscious dieter in the future. PMID- 1734531 TI - Infection due to Strongyloides stercoralis in patients with pulmonary disease. PMID- 1734532 TI - Contarini's condition. PMID- 1734533 TI - Pediatric journal club: unlikely abstracts of the pediatric literature. PMID- 1734534 TI - Gastrointestinal Kaposi's sarcoma as the first manifestation of acquired immunodeficiency syndrome. AB - Gastrointestinal Kaposi's sarcoma can occur in HIV-infected patients without previously diagnosed AIDS. Gastrointestinal symptoms in such patients should be thoroughly investigated because of the possibility of gastrointestinal Kaposi's sarcoma, despite the absence of the cutaneous form. The discovery of gastrointestinal Kaposi's sarcoma establishes the diagnosis of AIDS, as it did in our two patients. PMID- 1734535 TI - Atypical Kawasaki disease: coronary aneurysms and thrombocytopenia. AB - The patient we have described had coronary artery aneurysms pathognomonic for Kawasaki disease after a nonspecific febrile illness not meeting the classic clinical criteria. The child had significant thrombocytopenia, which in the past has been thought to militate against the diagnosis of Kawasaki disease. Echocardiography should be considered in febrile infants with thrombocytopenia of uncertain etiology. PMID- 1734536 TI - Group G streptococcal infection in an elderly patient. AB - It is only recently that GGS infections have been reported in the literature. These infections are rare, but they are serious when they occur. The organism is not very virulent, and serious infections occur only in patients who are immunocompromised, have some serious underlying disease such as cancer or intravenous drug abuse, or are at the extremes of age. I have described a fatal case of GGS meningitis and endocarditis in a previously healthy 84-year-old who had obtundation, irritability, and cellulitis. Many of the separately reported characteristics of serious GGS infections were present together in this case. PMID- 1734538 TI - Traumatic pseudoaneurysm of the posterior auricular artery. PMID- 1734537 TI - Gastroenteritis due to Salmonella sp: clinical and radiologic signs mimicking surgical peritonitis. AB - Salmonella infections most often are self-limited illnesses confined to the gastrointestinal system. They can, however, produce clinical and radiographic findings consistent with peritonitis. Careful attention to evaluation and treatment is required to avoid unnecessary surgery for what may initially appear to be a surgical condition. PMID- 1734539 TI - Stroke involving the midbrain and thalamus and causing 'nonfocal' coma. AB - We have described two patients who had coma without focal findings and who were found to have an ischemic stroke involving the midbrain and the thalamus. In both cases metabolic encephalopathy or drug overdose was initially suspected, but recognition of abnormal vertical eye movements led to the proper diagnosis. Examination of vertical eye movements in drowsy or comatose patients may be helpful in arriving at the correct diagnosis early and may prevent unnecessary investigations. PMID- 1734540 TI - Compliance with therapy for cervical dysplasia among women of low socioeconomic status. AB - This paper reports results of a project designed to examine factors related to compliance with referral for follow-up and treatment of cervical dysplasia. Women studied had cervical dysplasia diagnosed by Pap smear between May 1989 and April 1990. These women had regular follow-up at the gynecology clinic of the Reynolds Health Center in Winston-Salem or at one of 14 county health departments in northwestern North Carolina. Data were collected by chart review, and included age, race, place of residence, marital status, parity/gravidity, education, previous papillomavirus infections, method of payment, and previous Pap smear results. Patients were traced through the treatment protocol, and compliance was assessed at each appointment. In these women of low socioeconomic status, approximately one third of those referred for treatment of dysplasia were noncompliant with referral. PMID- 1734541 TI - Pneumocystis carinii pneumonia due to corticosteroids. AB - A patient receiving long-term corticosteroid therapy for asthma had two episodes of Pneumocystis carinii pneumonia (PCP) 8 years apart. She had no other causes of immunosuppression. Experimental evidence indicates that corticosteroid administration causes a reduction in T lymphocytes mediated by suppression of cytokines. Corticosteroid therapy is a rare but possible independent predisposition to PCP. PMID- 1734543 TI - Environmental illness and the public health. PMID- 1734542 TI - Asymptomatic heterotopic ovarian pregnancy. AB - An unruptured heterotopic ovarian pregnancy was diagnosed and managed surgically. We believe this is the first such case in a woman who was asymptomatic at presentation for an unrelated complaint. PMID- 1734544 TI - Consecutive orbital cellulitis associated with elevated serum immunoglobulin E. PMID- 1734545 TI - Positional headache due to spontaneous intracranial hypotension. PMID- 1734547 TI - The continuing problem of community-acquired bacterial pneumonia. PMID- 1734546 TI - Community-wide outbreak of hepatitis A among an Indian population in Oklahoma. AB - Between September 1983 and September 1984, 118 cases of hepatitis A were reported from Caddo County, Oklahoma. No common source was identified, and the epidemic curve suggested person-to-person transmission. In July 1984, enhanced control measures were implemented; these consisted of improvements in surveillance, standardization of case investigation, an expanded, although targeted, use of immune globulin, and a public awareness campaign. Control measures resulted in a decrease in the delay between onset of symptoms and case report (from 12 days to 4 days), an increase in the percentage of patients with confirmed cases interviewed (from 77% to 100%), an increase in the percentage of patients reporting contact with a previous case (from 39% to 72%), and an increase in the average number of household-like contacts per case (from seven to 27). Within two incubation periods of the implementation of enhanced controls, the outbreak ended. These data indicate that community-wide outbreaks of hepatitis A can be stopped with an intensive epidemiologic approach, coupled with the expanded and targeted use of immune globulin. PMID- 1734549 TI - Nutritional requirements in pregnancy. PMID- 1734548 TI - [Salpingoscopy]. PMID- 1734550 TI - The first 6 years of the Tygerberg Hospital lipid clinic. AB - The Tygerberg Hospital Lipid Clinic was established in July 1983. The demographic characteristics, lipid abnormalities, coronary risk factor profile, treatment status and 6-month follow-up lipid changes of patients seen during its first 6 years are summarised. During this period 329 patients were seen and complete lipograms were available for 312 of them. This patient population, consisting of 87.2% whites and 12.8% coloureds, represented a wide age range (2-69 years), various occupations and the whole spectrum of educational qualifications. The plasma cholesterol levels of 78.8% of the patients could be described as high risk, according to the cholesterol action limits of the Heart Foundation of Southern Africa, and 33.2% had low high-density lipoprotein cholesterol (less than 1 mmol/l) levels. Approximately 20% of the patients had familial hypercholesterolaemia and 31.1% were already on lipid-lowering medication before registration. The Lipid Clinic succeeded in improving the mean overall plasma cholesterol levels by 8% during the 6 months after registration and provided essential information for the planning of treatment strategies for patients with hypercholesterolaemia. PMID- 1734551 TI - Cardiac glycoside poisoning involved in deaths from traditional medicines. AB - Autopsy cases (from all areas of South Africa except the Cape Province) are referred for chemical investigation to the Johannesburg Forensic Chemistry Laboratory of the State Health Department. Over a 1-year period in 41 autopsies where death was presumed to have been caused by a herbal medicine, the presence of cardiac glycosides was sought and was found in 44%. Most of the cases were from the Transvaal, followed by Natal. Clinical histories of the patients revealed that gastrointestinal irritation was the most common syndrome experienced after traditional medicine administration (54%). It is concluded that in patients presenting with gastro-intestinal symptoms, presumably due to poisoning by traditional medicines, cardiac glycoside poisoning should be suspected. PMID- 1734552 TI - Cardiovascular causes of death at Tshepong Hospital in 1 year, 1989-1990. A necropsy study. AB - Cardiovascular disease is the third most common cause of death in Tshepong Hospital in the western Transvaal, and the most common cause of death in patients older than 35 years. A prospective study was undertaken which included limited necropsies in 90 of the 167 cardiovascular disease deaths over 1 year. A reliable mortality pattern for cardiovascular deaths is described. Additionally, attention is paid to co-existing conditions. Conditions relating to cardiovascular disease, such as hypertension, benign hypertensive nephrosclerosis, atherosclerosis and obesity, were also evaluated. Cerebrovascular conditions were found in 32% of cardiovascular deaths. Intracerebral haemorrhage was found in 50% and cerebral infarction in 29% of cases. Fifty-seven per cent of cardiovascular deaths were due to cardiac conditions, the most common being pulmonary hypertension (31%), dilated cardiomyopathy and chronic rheumatic valvular disease (17% each) and hypertensive heart disease (14%). Forty-nine per cent of subjects were hypertensive, while 40% exhibited benign nephrosclerosis and only 3% of the examined vessels had signs of severe atherosclerosis. Tuberculosis was present in 13% of cases. The clinical diagnosis was the same as the final necropsy diagnosis in 38% of cases. These results emphasise the importance of performing necropsies to obtain reliable mortality statistics. PMID- 1734553 TI - Urinary C-peptide in gestational diabetes. AB - Urinary C-peptide excretion was measured during the last trimester of pregnancy in 12 non-diabetic control women and in 32 women with gestational diabetes. The urine was sampled in two 12-hour periods between 06h00 and 18h00 and 18h00 and 06h00. At the end of the sampling period a fasting plasma sample was analysed for insulin, C-peptide, glycerol, free fatty acids and 3-hydroxybutyrate. The women with gestational diabetes had a significantly lower excretion of C-peptide during the daytime period. In this group women with diabetic heredity had lower C peptide excretion during the day-time and the 24-hour period compared with women without diabetic heredity. In the non-diabetic group there was significant correlation between body mass index and urinary C-peptide during the night-time and the total 24-hour period. The gestational diabetic women had fasting plasma concentrations of glycerol, free fatty acids and 3-hydroxybutyrate acid that were significantly above the levels found in the control group. PMID- 1734554 TI - Vaginal absorption of low-dose tranexamic acid from impregnated tampons. AB - Tranexamic acid (TA), an antifibrinolytic drug, is usually administered orally to women with menorrhagia. This route of administration is associated with adverse side-effects, therefore tampons impregnated with TA were used to assess the absorption of the drug across the vaginal epithelium. Blood levels of TA in group A (9 patients), who had one tampon inserted, and group B (10 patients), who had a tampon inserted at 2-hourly intervals so that a total of 3 tampons were administered over a 6-hour period, demonstrated absorption of the drug into the blood stream in low concentrations. PMID- 1734555 TI - Salivary calcium, magnesium, phosphate, chloride, sodium and potassium in pregnancy and labour. AB - Pregnancy and labour produce significant changes in salivary calcium, magnesium, phosphate and chloride when pregnant patients in labour are compared with non pregnant patients. There is a decrease in concentration of these constituents in the 3rd trimester of pregnancy followed by a marked increase when labour occurs. Magnesium and chloride are the constituents most significantly affected and show the largest increase during labour. Changes in saliva flow rate were accounted for and are not responsible for these changes noted. Sodium and potassium follow a similar pattern. When their levels are corrected for saliva flow rate changes, both show a significant increase with the onset of labour. PMID- 1734556 TI - The prevalence of potential pathogenic micro-organisms in the endocervix of pregnant women at Tygerberg Hospital. AB - The prevalence of potential pathogenic organisms cultured from the endocervix in 206 pregnant patients was: Ureaplasma urealyticum 63%, Mycoplasma hominis 39%, Candida albicans 20%, Chlamydia trachomatis 11%, Neisseria gonorrhoeae 7%, group B beta-haemolytic streptococcus 6% and Listeria monocytogenes 1%. The most common complications of pregnancy found were: preterm labour 14%, urinary tract infection 8% and premature rupture of membranes 4%. Significantly more patients in whom C. trachomatis or C. albicans were found delivered prematurely. Other organisms were not associated with preterm labour. PMID- 1734557 TI - Surgical glove powder and intraperitoneal adhesion formation. An appeal for the use of powder-free surgical gloves. AB - Intraperitoneal adhesion formation is a major cause of infertility and/or intestinal obstruction. Among the many well-known aetiological factors responsible for peritoneal inflammatory reaction is surgical glove powder; for example, cornstarch powder. A study was undertaken on 30 rats to determine whether cornstarch powder caused intraperitoneal adhesions. The rats were randomised into two groups under laboratory conditions. Laparotomies were performed on all the rats and trauma inflicted to the right uterine horn. The study group received cornstarch powder suspended in normal physiological salt solution intraperitoneally, and the control group received only normal physiological salt solution. Peritoneal adhesions were evaluated after 2 weeks and statistically analysed with a t-test and 95% confidence intervals. The study group showed a statistically significantly higher incidence of intraperitoneal adhesions (P = 0.0003). It is concluded that cornstarch, as used on surgical gloves, caused peritoneal adhesions and should therefore be removed before surgery. Powder-free gloves are more suitable for preventing adhesion formation. PMID- 1734558 TI - Feeding intervals and fat absorption in preterm babies. AB - Fat absorption studies were conducted on 18 preterm babies to determine whether continuous nasogastric feeding is as effective as intermittent feeding. The infants ranged from 1 290 g to 1 960 g in birth weight and were assessed at a mean postnatal age of 34 days. Each served as a control by receiving an evaporated milk 1-hourly, 2-hourly, 3-hourly or continuously in random order. Equivalent volumes of milk were ingested over each 3-day period irrespective of the method of feeding and the daily weight gain was similar for the various regimens. Stool transit times did not vary and fat absorption and retention showed no significant differences. Continuous feeding appears to be suitable for preterm babies, especially when there is a need to avoid abdominal distension. PMID- 1734559 TI - Nutritional recommendations for individuals with diabetes mellitus. AB - The diabetic diet is fundamentally a healthy diet, high in complex carbohydrates, high in dietary fibre, low in fat. A nutritionally adequate, mixed diet is satisfactory for most people with diabetes and special foods or food supplements are not required. The dietary recommendations directed towards the diabetic population are essentially similar to those recommended by most authorities for the population as a whole. Education of diabetic patients and their families and also individualised diet and meal planning are essential components in the management of diabetes mellitus. Weight loss and subsequent maintenance of a desirable body weight should be achieved when necessary. The amount of carbohydrate should be liberalised, including a wide variety of fibre-rich complex carbohydrates. In some individuals modest amounts of sucrose taken at meal times are acceptable. Foods with lower glycaemic indices should be offered on trial to people with diabetes. Total fat intake, especially saturated fat, should be restricted. More research is needed before recommendations regarding eicosapentaenoic acid supplementation can be made. Protein intake should be restricted to the Recommended Daily Allowance except in groups at risk of negative nitrogen balance. A restriction in salt intake is advised. Alcoholic beverages and nutritive and non-nutritive sweeteners may be used, but in moderate amounts. PMID- 1734560 TI - Erotomania in men. A report of 3 cases. AB - Erotomania is an uncommon psychiatric syndrome, rare in men. Three cases presenting in a forensic context are described. They support the contention that erotomania occurs secondary to another major psychosis. PMID- 1734561 TI - Confidentiality and AIDS. PMID- 1734562 TI - Guidelines on HIV infection. PMID- 1734563 TI - Guidelines on HIV infection. PMID- 1734564 TI - Guidelines on HIV infection. PMID- 1734566 TI - Unacceptable trends in the diagnosis of chronic fatigue syndrome. PMID- 1734565 TI - Infant mortality in South Africa. PMID- 1734567 TI - Hemoaccess site infection. AB - Infectious complications involving a hemoaccess graft or fistula are a significant cause of morbidity in patients on chronic hemodialysis. A review of 274 consecutive hemoaccess procedures identified 28 infections (an incidence of 10 per cent). Infections occurred in 27 polytetrafluoroethylene (PTFE) grafts. The predominant organism was Staphylococcus aureus. Partial excision resolved 14 of the 27 graft infections. The remaining 13 required complete removal. Surgical management required six arterial ligations and seven autogenous reconstructions. No limb ischemia or mortality was directly attributable to these procedures. One infection occurred in 48 autogenous fistulas (an incidence of 2 per cent). Although partial removal of an infected prosthesis was often sufficient, brachial artery ligation was well tolerated when required to control anastomotic infection. PMID- 1734568 TI - Aggressive axillary evaluation and adjuvant therapy for nonpalpable carcinoma of the breast. AB - While quadrantectomy or lumpectomy with axillary node sampling and dissection, or both, has been shown to be an equivalent alternative to modified radical mastectomy, some surgeons have begun to omit axillary dissection altogether in patients with extremely small tumors, believing that the axilla is unlikely to be involved. In reviewing the incidence of axillary involvement with 69 nonpalpable primary tumors in one community for nine years, 20 per cent of patients with invasive carcinoma had axillary involvement. In a four year review of the Connecticut Tumor Registry, we identified 137 instances of quite small invasive carcinoma of the breast that were 1 millimeter or less. Sixteen per cent of these patients had axillary involvement. The survival of patients with nonpalpable primary tumors and axillary involvement was no different than patients with palpable primary tumors and axillary involvement. Regardless of how small the primary tumor, the incidence of axillary disease is significant and failure to evaluate the axilla will result in understaging and inappropriate decisions about adjuvant therapy. PMID- 1734569 TI - Obscure bleeding in the gastrointestinal tract originating in the small intestine. AB - In the past 12 years, we operated upon 49 patients with bleeding lesions of the small intestine. After endoscopic examination and barium studies of the upper and lower gastrointestinal tract excluded esophagogastroduodenal and lesions of the colon and rectum, preoperative examinations consisted of technetium-99m pertechnetate scan, technetium-99m labeled erythrocyte scan, barium studies of the small intestine and selective visceral angiogram. In one patient, diagnostic laparotomy had to be done before any procedure because of severe bleeding and angiosarcoma of the ileum. The results of gross examination at operation revealed bleeding lesions in 40 patients. Special intraoperative localization procedures consisting of methylene blue injection through superselectively prepositioned angiographic catheter was done on eight patients, and intraoperative enteroscopy was done on 17 patients. These two procedures were complementary, having their own indications and limitations. Our regimen of preoperative and intraoperative localization procedures was effective in the management of bleeding small intestinal lesions. PMID- 1734570 TI - Effects of thromboxane synthetase inhibition on postburn mesenteric vascular resistance and the rate of bacterial translocation in a chronic porcine model. AB - It is known that thromboxane (TX)B2, the metabolite of the potent vasoconstrictor TXA2, is elevated markedly in the serum of the patients immediately postburn. We had shown that extensive thermal injury causes a reduction in mesenteric blood flow that can lead to bacterial translocation from the intestine. In this study, we tested the hypothesis that the TX synthetase inhibitor, OKY-046, prevents increased mesenteric vascular resistance (MVR) and decreases the rate of translocation of bacteria seen after extensive thermal injury. Pigs in groups 1 (n = 6) and 2 (n = 6) had third degree burns of 40 per cent total body surface area under general anesthesia and were resuscitated according to the Parkland formula. Pigs in group 2 received 10 milligrams per kilogram of OKY-046 as a bolus just before the burn and 10 grams per kilogram per minute for 16 hours as a continuous infusion. Pigs in group 3 (control, n = 6) underwent general anesthesia only and received daily maintenance fluids of lactated Ringer's solution, 2 milliliters per kilogram per hour. OKY-046 prevented the significant increase in MVR seen during the first eight hours after burn. The total peripheral resistance (TPR) showed an early increase and a late decrease in the burn group, while the cardiac index (CI) and temperature (T) significantly increased after 24 hours. Administration of OKY-046 kept TPR, Cl, and T remarkably stable. OKY-046 reduced the rate of translocation of bacteria seen in the burn group from 67 to 17 per cent. Our results show that the blockade of thromboxane synthesis by OKY-046 prevented the early mesenteric vasoconstriction and the late hyperdynamic response seen after thermal injury and was useful in reducing the incidence of postburn translocation of bacteria. PMID- 1734571 TI - Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium. AB - This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium. PMID- 1734572 TI - Epidural analgesia. AB - The most frequently used postoperative analgesia techniques are intramuscular injection (IM) and patient controlled analgesia (PCA). Recently, the use of epidural catheter injection (EPI) has been done with success. This study was done to prospectively compare these three techniques for postoperative analgesia after extensive operations upon the colon and rectum. Patients were randomized to one of three analgesia groups--IM, intramuscular morphine sulfate; PCA, patient controlled morphine sulfate, and EPI, epidural morphine sulfate. Data collected included age, time to first bowel movement, amount of narcotic, number achieving 75 per cent of preoperative forced vital capacity, postoperative pruritus, headache, nausea and vomiting, respiratory depression, atelectasis or pneumonitis. A visual analog pain scale was used to evaluate postoperative pain severity (0, no; 1, partial; 2, marked, and 3, total relief). Sixty-eight patients were eligible for study (IM, 19; PCA, 22; EPI, 23, and excluded, four). The EPI group required significantly less daily narcotic compared with either the IM or PCA groups (17.0 +/- 6.12 milligrams; 67.8 +/- 26.8 milligrams; 40.5 +/- 20.6 milligrams, respectively, less than 0.05 ANOVA) and total narcotic (81.3 +/- 31.3 milligrams; 355.4 +/- 147.7 milligrams; 215.3 +/- 105.4 milligrams, respectively, p less than 0.05 ANOVA). EPI achieves excellent pain control in more patients with a significantly lower dose of narcotics and significantly fewer pulmonary complications. Therefore, epidural analgesia is the optimal method of postoperative analgesia after extensive abdominal operations. PMID- 1734573 TI - Failure of percutaneous drainage of pancreatic abscesses complicating severe acute pancreatitis. AB - From 1981 to 1990, 14 of 70 patients hospitalized at our institution for severe acute pancreatitis were selected to undergo percutaneous drainage of pancreatic abscess, under computed tomographic (CT) scan guidance. Pancreatic abscess was defined, on contrast-enhanced CT scan, as an infected fluid collection without pancreatic necrosis. There were nine men and five women, ranging in age from 28 to 46 years. The main cause of pancreatitis was alcohol abuse (eight patients). Other causes were gallstones (two patients), hyperlipidemia (two patients), postoperative (one patient) and one unknown. Ranson criteria were available in ten patients and ranged from three to six. Percutaneous drainage was performed as the primary treatment in 13 patients and for removal of a residual collection postoperatively in one patient. In two critically ill patients, percutaneous drainage was performed as a temporizing measure. In 12 patients with well-limited hypodense collections, percutaneous drainage was expected to result in the definitive cure of the abscess. Pigtail drains (No. 14F), were inserted using local anesthesia and CT scan guidance. Two patients had two drains and 12 patients had only one drain. Two patients were definitively cured by percutaneous drainage and all other patients were operated upon for removal of infected necrosis. In this study, the lack of accuracy of contrast-enhanced CT scan in the diagnosis of peripancreatic necrosis is highlighted and that percutaneous drainage has a better efficiency in the treatment of residual collections postoperatively than as a primary treatment of infected fluid collections is illustrated. PMID- 1734574 TI - A prospective randomized study of abdominal rectopexy with and without sigmoidectomy in rectal prolapse. AB - Eighteen patients with full-thickness prolapse of the rectum were randomized to rectopexy alone (group 1) or with sigmoidectomy (group 2). Three months postoperatively, seven patients in group 1 and two in group 2 complained of severe constipation. One patient in group 1 and three patients in group 2 remained incontinent. The results of colonic marker studies showed a significant increase in the number of markers at day 5 for those in group 1 (preoperative, 7.7 +/- 2.6; postoperative, 14.6 +/- 2.2; t test, p less than 00.1) but no significant increase in group 2 (preoperative, 4.6 +/- 2.2; postoperative 6.8 +/- 2.3; t test, p less than 0.01). No significant changes or differences between the groups were seen in the anorectal angle on videoproctogram. The results of anorectal physiologic studies done postoperatively showed no differences between the groups in maximum resting pressure, sphincter length or saline solution infusion test; however, the patients in group 1 had a significantly greater rectal compliance (group 1, 0.24 +/- 0.02 millimeters mercury per milliliter; group 2, 0.1 +/- 0.02 millimeters mercury per milliliter; p less than 00.1). This may occur because the redundant loop of sigmoid colon causes hold-up of intestinal content and kinking at the junction between the sigmoid colon and the rectum. PMID- 1734575 TI - A modified technique for hemostasis during myomectomy. AB - By using a rubber shod Bainbridge type vascular clamp during myomectomy, the uterine blood supply coming from the ovarian artery can be interrupted medial to the ovary, allowing for adnexal perfusion. The gap in its clamp jaws provides a space for the fallopian tube to pass through undamaged. When used in conjunction with a tourniquet on the uterine arteries, excellent hemostasis is obtained. This simple and effective technique should prove to be a useful addition to the armamentarium of the gynecologic surgeon. PMID- 1734576 TI - The posterior intrahepatic approach for hepatectomy or removal of segments of the liver. AB - We have described herein an anterior and posterior perihilar intrahepatic approach to the hepatic sheaths of the segments of the liver. This approach allows early delineation of the anatomy of the liver and we believe it is a useful addition to the techniques available for operating on the liver. PMID- 1734577 TI - A simple method of removing residual intrathoracic air post-thoracotomy in children. AB - A simple and effective method of aspirating residual intrathoracic air is described. This method can be used when air leaks or persistent fluid accumulations are not expected. This technique may be easily adapted for use in older children or adults when similar circumstances are present. Standard postoperative monitoring, including serial roentgenogram of the chest, should be used to verify appropriate pulmonary re-expansion. PMID- 1734578 TI - A new and quick method for treating postmastectomy seromas. AB - The Seroma-Cath wound drainage system has proved to be a quick and effective method for treating postmastectomy seromas. It has been well received by the patients we studied, has eliminated frequent office visits, bulky dressings and the risk of wound infections. PMID- 1734579 TI - A method to prevent kinking of femorofemoral bypass grafts when using polytetrafluoroethylene. PMID- 1734580 TI - A double balloon occlusion technique for embolectomy in the trifurcation vessels. PMID- 1734581 TI - Gastric ulcer in diaphragmatic hernia. PMID- 1734582 TI - Improving the yield of biopsy for nonpalpable lesions of the breast. AB - Our early experience and frustration with needle localization biopsy of nonpalpable lesions of the breast led us to develop a protocol to improve diagnostic accuracy and management of patients with mammograms read as suspicious for malignancy. In this context and as part of the program, surgical and radiologic consultation is required prior to the decision to proceed with biopsy. In this article, our experience with that protocol is summarized and mammographic description with pathological findings is correlated. In a series of 200 consecutive patients who underwent biopsies, we have achieved a positive rate of 37 per cent. Only 2 per cent of those lesions with round, oval or lobulated borders were malignant, while irregular or spiculated lesions were malignant in 69 per cent of instances. We conclude that careful adherence to this protocol and to radiologic principles of contour analysis can substantially increase the yield of needle localization biopsy. PMID- 1734583 TI - Critical review of the treatment of pyogenic hepatic abscess. AB - A retrospective review of 29 consecutive patients with pyogenic hepatic abscesses was undertaken to ascertain the efficacy of various treatments. Percutaneous routes were used 25 times (aspiration alone in 16 and with concomitant drainage in nine), as a primary step 22 times and for recurrent abscesses, three times. An operation was required in nine patients; initially in five and after percutaneous treatment in four. Antibiotics alone were used twice. There were seven deaths, two after antibiotics alone and five after initial percutaneous aspirations. There were six recurrent abscesses, all but one after percutaneous aspiration. Our results suggest that antibiotics alone and percutaneous aspiration alone are inadequate in the treatment of pyogenic hepatic abscesses; percutaneous management is valid provided concomitant drainage is used, and that once the abscess has been successfully handled percutaneously, surgical treatment is a safe alternative as a first step, for abscesses recurring after percutaneous management, or for removal of the primary cause of the disease. PMID- 1734584 TI - [The potentials and limits of the radiotherapy of laryngeal carcinoma]. AB - Early stage glottic carcinoma can be treated with primary radiotherapy reaching equally good results compared to primary surgery; for supraglottic carcinoma surgery offers only slight advantages over primary radiotherapy. Tumor control for recurrences is considerably improved by salvage surgery. The use of primary radiotherapy allows improved or at least preserved voice and reduced rates of acute complications and late treatment sequelae. However, treatment duration is longer and probably more expensive compared to function preservation microlaryngoscopic surgery. Which treatment approach is chosen, depends on individual patient factors and specific conditions in the clinical setting. In any case, primary radiotherapy deserves a stronger say in the early stage tumor situation. In our institution early stage supraglottic carcinomas undergo primary surgery. Advanced carcinomas (T2b and more) are rarely suited for primary radiotherapy with the exception of some very confined T3 tumors. Surgical approaches should be favoured, since they provide a detailed pathohistological tumor staging including R-classification, which would be lacking using primary radiotherapy. There are clear reasons to treat the lymph nodes for glottic carcinomas stage T2b and more and for all supraglottic carcinomas with radiotherapy. Specific risk factors are: tumor at the margins of the incision (R1), infiltration of the cartilage and pre-epiglottic space, paratracheal and subglottic extension of more than 1 cm, perineural invasion, grade III and IV as well as emergency tracheostomy. Postoperative radiotherapy should be given to the lymph nodes for all positive neck-dissections. New therapeutic approaches are on the horizon, which may improve the results of radiotherapy even for advanced larynx carcinomas, like hyperfractionation radiotherapy and simultaneous radio chemotherapy combined enoral resection and postoperative radiotherapy may yield larynx preservation even for advanced stages. New imaging techniques allow an improved staging and predictive radiobiological assays may play a major role in tumor prognosis. PMID- 1734585 TI - [High-dose-rate brachytherapy of prostatic carcinoma with iridium 192]. AB - In the therapy of localized prostatic cancer the radical prostatectomy shows good results within a five-year interval with no evidence of disease in nearly 90%. An important alternative is the radiotherapy by external beam or interstitial technique with iodine, gold or iridium. We use the high dose rate technique with Ir-192. In this technique five to seven hollow needles are placed in the prostate from perineal punctures under transrectal sonographic control. The three dimensional brachytherapy planning is done according the actual needle position. A computer program calculates the radiation dose and distribution for each needle by adjustment of time and stops of the Ir-implants. The Ir-192 is temporary loaded twice with 9 Gy supplemented with external beam radiation (18 x 2 Gy). Since 1985 29 patients with localized tumor (T1-T3, N0, M0) have been irradiated. 21/29 had a pelvic lymphadenectomy before. In 85% of the patients were seen no side effects. Only one patient had a serious complication through a recto-vesical fistula. Out of the 21 followed-up patients 16 were in full remission, three had an androgen deprivation because of progression. A local tumor control could be demonstrated by cytology in 70% of the patients. This rational technique seems to be an alternative for patients not eligible for a radical prostatectomy. PMID- 1734586 TI - Irradiated volume and arytenoid edema after radiotherapy for T1 glottic carcinoma. AB - From May 1982 through December 1986, 116 T1 glottic carcinomas were treated with radiotherapy in a prospective randomized study to determine the effect of radiation field size. Patients were treated with a total dose of 60 Gy over six weeks using 4 MV X-ray, wedge filter and shell. Local control rates treated with a field size of 5 x 5 cm2 and 6 x 6 cm2 were 93% and 95%, respectively. Persistent laryngeal edema occurred in 4% of cases treated with 5 x 5 cm2 and 21% with 6 x 6 cm2 (p less than 0.02). The rate of late laryngeal edema was dependent upon the treatment volume. A larger treatment field yielded a higher minor complication rate without improvement of local control rate. PMID- 1734587 TI - [The sensitometric recording of verification films in high-volt therapy]. AB - Film sensitometric determinations under high voltage conditions, i.e. under radiation at an energy of at least 1 MeV, are very time-consuming and material intensive, because, with increased dose of radiation, several films have to be exposed and densitometrically measured. These results then form the basis of the preparation of the density curve. This paper describes, how, by applying a special technique (so-called sensitometric double exposure method), film sensitometry under high voltage radiation conditions may be considerably simplified and shows how the necessary resources (i.e. step-wedge = stepped photometric absorption wedge) can be made quite simply. The method described uses film DOT-I and DOT-II by Dupont, whereby the exposure of the step wedge takes place on a linear accelerator with a photo energy of 10 MeV. The results show that with a target volume dose up to 1.5 Gy the DOT-II film yields the better results, while with doses above 1.5 Gy, usage of DOT-I film is recommended. PMID- 1734588 TI - [3-D visualization of dose distributions in CT image volumes]. AB - The 3D-visualization of the entire spatial radiation dosage in cooperation with the 3D-radiation volume requires several data volumes. The structure of the interface between the 3D-treatment planning program "ProPlan" and the 3D-imaging system "VOXEL-MAN" is explained. The first results in the radiological application point out the possibilities of the complex registration of dose distributions and the critical examination of the irradiation technique. PMID- 1734589 TI - [The prevention of mucosal lesions during oropharyngeal irradiation with a dental filling shield]. AB - In patients with metallic dental fillings radiation therapy to the oral cavity can cause mucous membrane lesions, which are more severe than expected. They appear as circumscribed erosions, opposite to metallic fillings and are caused by an increase in radiation dose through secondary radiation due to the higher density and atomic number of the filling material. This dose increase can be directly measured with 0.1 mm thin sheets of graphite-loaded TLD's (LiF, Vinten). For Co-60 gamma rays a commercial amalgam filling caused a dose increase by a factor of 1.7. The half value layer for this additional radiation was measured to be approximately 0.4 mm tissue. In order to avoid painful mucous membrane ulcerations which are even more a problem if hyperfractionated treatment schedules are used, we constructed individual dental shields for each patient. As shielding material we used a dental impression material (Optosil P+1 Bayer). This method was tested in 35 patients, in all of them circumscribed mucous membrane ulcerations could be avoided. The method proved to be fast and simple and was very well tolerated by all patients. PMID- 1734590 TI - [The print-out of CT images and radiation treatment planning data on a laser printer]. AB - We introduce a program for the digital output of CT images with overlaid isodose maps to a laser printer. The high quality prints permit the additional output of treatment planning data on the same sheet. PMID- 1734591 TI - RBE and OER measurements on the p(66) + Be neutron beam at Faure, South Africa. AB - Results reported are for single dose exposures and refer to 60Co-gamma irradiation. The RBE determined by V79 cell survival and based on the Do ratio was found to be 1.70 +/- 0.4 ranging from 1.5 to 1.8. In the case of the regeneration of mouse jejunal crypts the RBE was calculated at ten cell survival and was found to be 1.68. The maximum acute mouse skin reaction at a skin score of 2.0 was found to be 2.1 while the average skin reaction was 1.7. Growth retardation of Vicia faba bean roots measured at the level of 50% indicated an average RBE of 3.0 and a range of 2.7 to 3.7. The OER obtained for V79 cell survival was found to be 1.7 to 1.8. Comparison is made with the RBE and OER measurements for the neutron facilities at Clatterbridge, Fermilab and Louvain-la Neuve which produce neutrons by the same nuclear reaction and whose physical specifications closely resemble those of the Faure neutrons. This comparison indicates that the Faure beam shows no unusual biological features and that its biological effectiveness is in line with that expected from its physical characteristics. PMID- 1734592 TI - [The experimental brachytherapy of rhabdomyosarcoma R1H in the rat with iodine 125 seeds]. AB - Rhabdomyosarcoma R1H of the rat with a volume of 1.2 cm3 were treated by implanting three to eight iodine-125 seeds (20.4 MBq). While implantation of inactive seeds had no influence on tumour growth, implantation of three or four seeds caused a reduction in tumour growth rate. Local tumour control was achieved in 71 and 80% of the tumours after implantation of seven and eight seeds, respectively. PMID- 1734593 TI - [The psychosocial care of cancer radiology patients--the requirement, subjective need and acceptance]. AB - The topic of the investigation was the discrepancy between the documented objective need for psychosocial support of cancer patients on the one hand, and of the patient's little subjective needs on the other, the latter resulting in only low acceptance of care offered. In an empiric study the attitude of 38 radio oncological patients (29 female, nine male) toward psychosocial support was investigated. The study revealed a tendency, independent of sex, that may be described as a social retreat (e.g. emphasis on personal independence, desire not to burden anybody, to hold back own interests and feelings, to be of help rather to others). We interpret this attitude as a specific reaction of coping with the problem, attempting at self-stabilisation. PMID- 1734594 TI - Indoor radon and lung cancer. Estimating the risks. AB - Radon is ubiquitous in indoor environments. Epidemiologic studies of underground miners with exposure to radon and experimental evidence have established that radon causes lung cancer. The finding that this naturally occurring carcinogen is present in the air of homes and other buildings has raised concern about the lung cancer risk to the general population from radon. I review current approaches for assessing the risk of indoor radon, emphasizing the extrapolation of the risks for miners to the general population. Although uncertainties are inherent in this risk assessment, the present evidence warrants identifying homes that have unacceptably high concentrations. PMID- 1734595 TI - Primary care physicians' refusal to care for patients infected with the human immunodeficiency virus. AB - We conducted a telephone survey of a random sample of office-based primary care physicians in Los Angeles County to determine their practice experiences with patients infected with the human immunodeficiency virus (HIV). Telephone interviews included questions related to the physicians' experiences evaluating patients for HIV infection during the past 6 months and the presence of HIV infected patients in their practices. Those without HIV-infected patients were asked if this was because they had not encountered such patients, because those patients had died, or because the physicians had chosen to refer these patients elsewhere or the patients had gone elsewhere for care. Of physicians who participated in the survey, 78% had evaluated a patient for HIV infection in the past 6 months; 34% were currently providing primary care for infected patients; and 36% had elected to refer HIV-infected patients elsewhere, or their patients had elected to find other physicians. In all, 48% of physicians in the sample had elected not to care for, or said they would not provide care for, patients with HIV infection. Among Los Angeles County primary care physicians, 36% have refused to provide continuing care for HIV-infected patients and another 12% indicated their unwillingness to do so should such patients present themselves for care. As of 1991, the reservoir of primary care physicians in Los Angeles not yet involved with but willing to care for HIV-infected patients is relatively small (15%). PMID- 1734596 TI - Home oxygen therapy under Medicare. A primer. AB - Medicare recently implemented a new, strict, and complex home oxygen policy and a new oxygen prescription form. Unfortunately, the lack of instructions for the form has led to confusion, frustration, and suboptimal treatment. Long-term oxygen therapy prolongs survival, ameliorates hypoxic organ dysfunction, and improves exercise endurance. Indications for therapy include hypoxemia caused by cardiopulmonary diseases, hypoxemia that occurs with sleep or exercise, and hypoxemic organ dysfunction. Patients should be stable and have an arterial blood oxygen tension (PaO2) of 55 mm of mercury (7.3 kPa) or less or arterial blood oxygen saturation (SaO2) of 88% or less. There should be evidence of hypoxic organ dysfunction when the (PaO2) is 56 to 59 mm of mercury (7.4 to 7.8 kPa) or the SaO2 is 89%. A medical review by the insurance carrier is required if oxygen is to be prescribed when hypoxemia is less severe--if the PaO2 is 60 mm of mercury (8.0 kPa) or more or if the SaO2 is 90% or more. The instructions for oxygen flow, duration, and equipment must be explicit to ensure adequate therapy. An oxygen concentrator with a small oxygen cylinder portable system fulfills most needs. Oxygen cylinders may be used at low flows for patients who require therapy only during sleep or where electrical power is unreliable. A liquid oxygen system may be prescribed for active patients. Portable equipment should be provided in addition to stationary equipment when patients have resting hypoxemia. Portable equipment alone is sufficient when there is exercise-related hypoxemia with normal oxygenation at rest. Newly developed oxygen-conserving devices may offer longer ambulatory times and possibly lower operating costs. When home oxygen therapy is started in the hospital, the Certificate of Medical Necessity should be completed and patients should be trained to use the equipment before discharge. PMID- 1734597 TI - Screening persons aged 65 and older for coronary heart disease risk factors. AB - Because of limited clinical investigations addressing the effectiveness of intervention to reduce known risk factors, it is difficult for primary care physicians to decide on which coronary heart disease risk factors to continue to screen for among older patients. The recently published report of the United States Preventive Services Task Force, using explicit screening criteria, has recommended that several risk factors be investigated for use among older adults. Recent longitudinal studies have found that a number of risk factors persist with advancing age-hypertension, left ventricular hypertrophy, impaired glucose metabolism, elevated cholesterol levels, obesity, smoking, physical inactivity, decline in vital capacity, and increased heart rate. Screening to identify many of these risks and treatment and counseling to modify them appear to improve survival. Evidence is less clear that diabetes mellitus and elevated cholesterol levels have the same significance for men and women as they age. Left ventricular hypertrophy and diabetes seem particularly important as risk factors for older women, whereas a high heart rate may be a greater risk for men. PMID- 1734598 TI - Health behavior and experiences of physicians. Results of a survey of Palo Alto Medical Clinic physicians. AB - The results of a health practice questionnaire submitted to the 152 physician members of the Palo Alto Medical Clinic, 126 of whom responded, indicate a generally favorable profile of preventive medicine strategies. Physicians generally smoke less, drink about the same, exercise more, and use their seat belts more than the population at large. They also can expect to live longer. These results are compared with those of other physician surveys and surveys of the general public. PMID- 1734599 TI - Current issues concerning the epidemiology of acquired immunodeficiency syndrome and human immunodeficiency virus. AB - This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. PMID- 1734600 TI - Pulse oximetry and capnography in intensive and transitional care units. PMID- 1734601 TI - Ventilator management of severe asthma. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in internal medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in internal medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Internal Medicine of the California Medical Association, and the summaries were prepared under its direction. PMID- 1734602 TI - Recent advances in diagnostic tests for syncope. PMID- 1734603 TI - Primary human immunodeficiency virus infection--will you miss the diagnosis? PMID- 1734604 TI - Pressure support mechanical ventilation. PMID- 1734605 TI - Cardiovascular risk factors in people older than 65. PMID- 1734606 TI - Benefits of dual-chamber pacemakers. PMID- 1734607 TI - Diabetic nephropathy revisited. PMID- 1734608 TI - Treatment of chronic hepatitis C with recombinant interferon alfa. PMID- 1734609 TI - Transesophageal echocardiography. PMID- 1734610 TI - Advance medical directives. PMID- 1734611 TI - Clinical use of erythropoietin. PMID- 1734612 TI - Cognitive decline with nortriptyline use in a patient with dementia of the Alzheimer's type. PMID- 1734613 TI - The physician as erotomanic object. PMID- 1734614 TI - Occult Enterobacter aerogenes pneumonia diagnosed by indium 111-labeled leukocyte scan. PMID- 1734615 TI - Communicating bad news. PMID- 1734616 TI - Indoor radon--what is to be done? PMID- 1734617 TI - A medical practice opinion program. PMID- 1734618 TI - Nervous about ticks--assessing Lyme disease risk in San Diego County. PMID- 1734619 TI - A medical practice opinion program. PMID- 1734620 TI - Mistreatment of gay medical students. PMID- 1734621 TI - HIV incidence in Nevada? PMID- 1734623 TI - Durable power of attorney for health care. PMID- 1734622 TI - Thyroid dysfunction and false pregnancy. PMID- 1734624 TI - Secretin and the endocrine pancreas. Structure-activity relationship between secretin and the release of glucose-regulated hormones from isolated pancreatic islets. PMID- 1734625 TI - Do forehead lifts lift or unfurl? AB - Forehead lifts are becoming increasingly more popular as an adjunct to facial rejuvenation. Considerable confusion exists as to how much the eyebrow should be elevated and how much scalp should be removed to achieve this goal. In an effort to evaluate this question, we have reviewed our recent forehead lift experience. These were done with forehead flap dissection down to glabella and supraorbital ridge, partial resection of corrugator supercilii, procerus, and frontalis muscles, and limited skin resection. We suggest that a natural-appearing, rejuvenating forehead lift should unfurl facial wrinkles without excessive eyebrow elevation. Technical maneuvers to obtain this goal are discussed. PMID- 1734626 TI - Perioral dermabrasion: clinical and experimental studies. AB - From 1985 through 1989, 54 patients with wrinkles around the lips and in the chin area were treated by dermabrasion. Significant improvement, lasting longer than three years, was achieved using both types of abrading tool: the wire brush and the diamond fraise. The side effects of dermabrasion were permanent but very slight bleaching in 66% of the patients and formation of milia in less than 20%. The surgical technique is described in detail. Dermabrading tools were tested at different speeds on excess cheek skin at facelift. Histological examination showed that the diamond fraise left a smooth abraded surface and the wire brush left an uneven surface. EMLA cream, usually used for skin surface analgesia, was tested as an adjunct to anesthesia in dermabrasion. EMLA's analgesic performance alone was insufficient in the sensitive perioral region, but it elevated pain threshold and decreased the required amount of local anesthetic solution. Five types of dressing were used and the speed of epithelialization and postoperative comfort were compared. At present Vigilon is the most suitable dressing for dermabrasion. The main advantage of dermabrasion over the chemical peel is the absence of severe depigmentation. PMID- 1734627 TI - Secondary rhinoplasty via transcolumellar incision. AB - The transcolumellar rhinoplasty was used in 90 patients with severe nasal sequelae caused by one or more previous surgical interventions. In each case the deformity was located mainly on the nasal tip making it extremely difficult to correct with conventional surgical procedures. We chose the transcolumellar rhinoplasty procedure to avoid another failure for these patients who sought complete resolution of their problem. At the same time, the technique provides a more secure surgical field to make a definitive diagnosis and to treat the sequelae properly. PMID- 1734628 TI - Suction lipectomy: the gold triangle at the neck. AB - Cervical suction lipectomy is a simple procedure that poses no technical problems. Evaluation of the amount of fat to remove is easy since the deposit is superficial and the skin considerably more supple than over the body. Although postoperative changes may be slow to develop, the skin usually exhibits outstanding adaptability in this area and this adaptability improves over time. On the basis of these favorable features occurring in the same location, a cervical gold triangle can be defined. In this area, where excellent results can be expected, indications of suction-assisted lipectomy can be very broad. PMID- 1734629 TI - Cornerstones in reconstructive plastic surgery: Argentinian development of muscular, myocutaneous, and fasciocutaneous flaps. AB - This article pays tribute to two Argentinian surgeons whose work has been published in their local journals but is unknown internationally. Goldtraj's pioneering work on the treatment of vascular ulcers of the leg using a muscular flap, presented in 1954, and Spadafora's work on the treatment of tissue defects with myocutaneous and fasciocutaneous flaps, presented in 1964, are discussed. Both papers deserve a place among the pioneering contributions on the subject of muscular as well as myocutaneous and fasciocutaneous flaps. PMID- 1734630 TI - Bury-and-knot suturing method. AB - An innovative bury-and-knot suturing method for firm fixation of a graft through a small skin incision is described and two clinical cases presented. PMID- 1734631 TI - Twenty years of experience with particulate silicone in plastic surgery. AB - The use of particulate silicone in plastic surgery involves the introduction of solid silicone into the body. The silicone is in small pieces in order for it to adapt to the shape of the defect. This way large quantities can be introduced through small incisions. It is also possible to distribute the silicone particles from outside the skin to make the corrections more regular. This method has been very useful for correcting post-traumatic depressions in the face and all areas where the depression has a rigid back support. We consider it the treatment of choice for correcting the funnel chest deformity. PMID- 1734632 TI - Bioplastique: a new biphasic polymer for minimally invasive injection implantation. AB - The search for prosthetic materials that are biocompatible, nontoxic, and permanent led the authors to develop a micronized, inert, biphasic polymer particle for permanent soft tissue augmentation which neither migrates nor is absorbed by the body. Placed in a bioexcretable gel carrier, these textured microparticles are easily implanted using a specially designed blunt-tipped cannula with local anesthesia on an outpatient basis. Research using this implant material, Bioplastique (Bioplasty, St. Paul, MN), in rabbits has shown that when the textured particle size is maintained within a critical range, neither particle migration nor storage disease occurs. The gel carrier is rapidly phagocytized and replaced by fibrin matrix within a few days. Host collagen then gradually forms a fibrotic capsule around each textured particle, making use of the naturally occurring foreign body reaction to create a stable inplant. After being followed for over two years, Bioplastique has proven to be useful in many clinical applications with few complications. PMID- 1734633 TI - Bioplastique: specific technical advice on its use and possible complications. PMID- 1734634 TI - Twelve months of experience with Bioplastique. AB - Over a 12-month period, 40 patients were treated for various facial defects using a new, injectable microimplant material--Bioplastique. Areas treated included cheeks, chins, lips, nasolabial lines, nasoglabellar lines, infraoral lines, noses, and miscellaneous depressions. Patients were observed for overcorrection, inflammation, morbidity, allergic reaction, or other complications. Both patient and physician satisfaction were recorded. Use of Bioplastique was found to offer permanent results by means of a quick, simple procedure administered under local anesthesia without scarring. With proper training and a good "eye," subtle corrections are possible. The author anticipates wide application of Bioplastique for the treatment of numerous soft tissue deficiencies. PMID- 1734635 TI - Utilization of injectable microimplants in aesthetic facial surgery. AB - The authors present a series of 74 patients that underwent injections of a biphasic copolymer (Bioplastique) to improve the facial contours or to fill deep creases and folds. The followup period was ten months. This preliminary report could be useful in defining the possibilities of the new product. PMID- 1734636 TI - Mammalian response to subdermal implantation of textured microimplants. AB - The development of small, textured implant particles suspended in a hydrogel has allowed for subdermal injection therapy to fill tissue defects. The microimplant particles were placed subdermally into the ears of white New Zealand rabbits in order to characterize the foreign body response and the permanence of the implant. Serial micrometer readings were performed on the implant sites to determine any change in thickness of the augmentation following baseline measurement. An initial increase in the thickness was noted approximately 20-30 days postimplantation, as expected. A stable thickness was noted for the remainder of the experiment. Serial histological sections were performed at irregular intervals from one week to one year. Histology demonstrated a mild foreign body response with collagen surrounding each individual microimplant particle. The response was stable after 30-40 days and has remained stable for over one year. It was determined that the histology demonstrated a Boros 1A type, or nonimmunogenic, low-turnover foreign body reaction. PMID- 1734637 TI - Enhancement of the efficacy of isosorbide dinitrate by captopril in stable angina pectoris. AB - This study was designed to assess whether the angiotensin-converting enzyme inhibitor captopril could potentiate the efficacy of a single dose of oral isosorbide dinitrate (ISDN) in patients with coronary artery disease. Fourteen men (mean age 53 years) with stable angina pectoris were studied. In each patient the efficacy of placebo, captopril (50 to 100 mg), ISDN (10 mg), and a combination of captopril (50 to 100 mg) and ISDN (10 mg) was assessed by repeated exercise treadmill tests performed before and 1, 2, 3 and 6 hours after administration of a single dose. A single-blind, randomized technique was applied. According to the mean data in the whole group of 14 patients, captopril alone produced no improvement in exercise duration to the onset of angina and to angina of moderate severity compared with placebo. The magnitude of ST-segment depression did not significantly change after captopril administration. ISDN alone significantly increased exercise duration to onset of angina and to angina of moderate severity (antianginal effect) and decreased the magnitude of ST segment depression (antiischemic effect) 1 to 3 hours after administration. Combined administration of ISDN and captopril resulted in more expressed antianginal and antiischemic effects; at 2, 3 and 6 hours these effects with ISDN plus captopril were significantly more pronounced than those with ISDN alone. According to individual data, the most marked potentiation of ISDN efficacy was observed in patients who had poor response to ISDN alone. In all 6 patients in whom ISDN alone was ineffective, after the addition of captopril the desired antianginal effect was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734638 TI - Identifying coronary artery disease in women by heart rate adjustment of ST segment depression and improved performance of linear regression over simple averaging method with comparison to standard criteria. AB - Performance of exercise electrocardiography for the detection of coronary artery disease (CAD) in women has been limited by relatively poor sensitivity and specificity of standard test criteria. Recent studies suggest that diagnostic methods incorporating heart rate (HR) adjustment of ST-segment depression during exercise may improve the accuracy of exercise testing in women, but the relative performance of different rate-adjusted methods for this purpose is unknown. To assess the effect of gender on relative test performance of the ST-segment/HR (ST/HR) slope, the simple ST/HR index, the HR-recovery loop, and standard ST depression criteria for the identification of CAD, the exercise electrocardiograms of 254 patients with known or suspected CAD (67 women and 187 men) and of 150 clinically normal subjects (29 women and 121 men) were analyzed. Specificity of each method was comparable in men and women: ST/HR slope 98% (118 of 121) vs 97% (28 of 29), ST/HR index 97% (117 of 121) vs 97% (28 of 29), and HR recovery loop 96% (116 of 121) vs 93% (27 of 29). In contrast, although there was no difference in sensitivity of the ST/HR slope (95% [177 of 187] vs 93% [62 of 67]; p = not significant [NS]) or HR-recovery loop (90% [168 of 187] vs 87% [58 of 67]; p = NS) between men and women, the ST/HR index was less sensitive for CAD in women than in men (82% [55 of 67] vs 93% [173 of 187]; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734639 TI - Usefulness of exercise-induced ST-segment depression in the inferior leads during exercise testing as a marker for coronary artery disease. AB - Multiple lead systems are shown to have a higher sensitivity than that of single leads for detecting coronary artery disease (CAD) during exercise testing, but the value of ST-segment depression isolated to the inferior leads is questionable. To ascertain the diagnostic accuracy of inferior limb lead II compared with that of precordial lead V5, a retrospective analysis of 173 men was performed (108 in a training population and 65 in a validation cohort). All patients had a standard exercise test and underwent diagnostic coronary angiography within 15 days of the exercise test (range 1 to 65). Sixty-three patients had greater than or equal to 1 coronary stenoses greater than or equal to 70%, or left main lesion greater than or equal to 50%, whereas 45 patients in the training population did not. Exclusion criteria were female sex, left ventricular hypertrophy, left bundle branch block or resting ST-segment depression on the baseline electrocardiogram, previous myocardial infarction or revascularization procedures, and any significant valvular or congenital heart disease. Lead V5 had a better combination of sensitivity (65%) and specificity (84%) (chi-square = 24.11; p less than 0.001) than that of lead II (sensitivity 71%, specificity 44%) (chi-square = 2.25; p = 0.13) at a single cut point, and this improved specificity was substantial (95% confidence interval for observed difference 22 to 58%). Receiver-operating characteristic curve analysis also revealed that lead V5 (area = 0.759) was markedly superior to lead II (area = 0.582) over multiple cut points (z = 3.032; 2p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734640 TI - Comparison of one-, six- and 24-hour ambulatory electrocardiographic monitoring for ventricular arrhythmia as a predictor of mortality in survivors of acute myocardial infarction. CAMIAT Pilot Study Group. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. AB - To compare 1-, 6- and 24-hour ambulatory electrocardiograms for prediction of mortality after acute myocardial infarction (AMI), all patients with AMI hospitalized in Hamilton, Ontario during 1 year were identified. There were 683 patients discharged alive after AMI. One-, 6- and 24-hour ambulatory electrocardiographic results were available in 565 patients, and follow-up mortality data at 1 year was available in 560. Mean age of the patients was 64 years; 160 (29%) had previous AMI and 105 (19%) had had congestive heart failure. One hundred and fifty-two patients (27%) were receiving beta blockers, and 31 (6%) were receiving antiarrhythmic drugs. Regression modeling of survival times up to 1 year showed that all 3 durations of recording were univariate predictors of mortality. Using greater than 10 ventricular premature complexes/hour as the criterion of a positive test, neither the 6- nor 24-hour data contained statistically significant residual explanatory power after the 1-hour data were accounted for by the model. The longer durations of recording increased sensitivity at a cost of decreased specificity. The positive and negative predictive values of the 3 durations of recording were virtually identical. The presence of ventricular tachycardia was not a significant predictor of mortality in this population. There appears to be no benefit to ambulatory electrocardiographic recordings greater than 1 hour when they are to be used for prediction of 1-year mortality after AMI. PMID- 1734641 TI - Clinical angiographic and histologic correlates of ectasia after directional coronary atherectomy. AB - Directional coronary atherectomy can cause ectasia (final area stenosis less than 0%), presumably due to an excision deeper than the angiographically "normal" arterial lumen. In a multicenter series in which quantitative coronary arteriography was performed after directional atherectomy in 382 lesions (372 patients), ectasia after atherectomy occurred in 50 (13%) lesions. By univariate analysis, ectasia was seen more often within the circumflex coronary artery (p = 0.008), in complex, probably thrombus-containing lesions (p = 0.015), and with higher device:artery ratios (p less than 0.001). Ectasia occurred less often in lesions within the right coronary artery (p = 0.008). Histologic analysis demonstrated adventitia or media, or both, in all patients with angiographic ectasia. Repeat angiography was performed in 188 of 271 eligible patients (69%) 6.1 +/- 2.4 months after atherectomy. Restenosis, defined as a follow-up area stenosis greater than or equal to 75%, was present in 50% of patients without procedural ectasia and in 70% of patients with marked ectasia (residual area stenosis less than -20%; p = 0.12). It is concluded that excision beyond the normal arterial lumen may occur after directional coronary atherectomy, related, in part, to angiographic and procedural features noted at the time of atherectomy. Restenosis tends to occur more often in patients with marked ectasia after coronary atherectomy. PMID- 1734642 TI - Pulmonary thallium-201 uptake following dipyridamole-exercise combination compared with single modality stress testing. AB - Angiographic and clinical determinants of pulmonary uptake of thallium-201 were assessed in a laboratory setting where supine bicycle exercise is used for stress testing in the absence of limiting pharmacologic or physical factors, and where symptom-limited exercise is added to intravenous dipyridamole infusion in other cases. Angiographic correlation was available in 400 patients, including 130 tested with exercise, 94 in whom only handgrip or abbreviated bicycle exercise could be used after dipyridamole, and 176 in whom intravenous dipyridamole was combined with a significant level of exercise. For each test mode, lung/myocardial ratios on the immediate image were highly correlated (p less than or equal to 0.001) with a score based on the number of critical coronary artery stenoses, with grading by contrast ventriculography, and with the number of stenosed (greater than or equal to 50%) arteries; relationships (p less than 0.05) to history of myocardial infarction and to gender were also present. Multiple regression analysis showed the critical stenosis score and ventricular dysfunction to be the only significant determinants. When dipyridamole based tests were compared with exercise, curves of receiver-operating characteristics showed a tendency to better diagnostic performance. When dipyridamole is incorporated in stress testing, the value of increased lung uptake as an ancillary diagnostic sign is similar to that established for exercise. PMID- 1734643 TI - Survey of practicing cardiologists in Maryland on their choice of thrombolytic therapy for acute myocardial infarction. AB - In November 1990, we surveyed 160 practicing community cardiologists in the state of Maryland and 20 academic cardiologists at the University of Maryland Medical Center to determine each individual's preference for aggressive versus nonaggressive therapy for various presentations of acute myocardial infarction. The survey was repeated in April 1991 following a report of the results of the Third International Study of Infarct Survival. All 100 responding cardiologists chose aggressive therapy to manage an early (less than 2 hours) acute anterior myocardial infarction in a 50-year-old patient. However, less aggressive therapy was chosen by many community cardiologists for management of early inferior acute myocardial infarction or for elderly patients. Most community cardiologists chose tissue plasminogen activator as their thrombolytic drug of choice, whereas university cardiologists favored streptokinase. Although there were substantial shifts in choice of thrombolytic agent on the repeat survey, most community physicians still chose tissue plasminogen activator over the less expensive streptokinase. PMID- 1734644 TI - Survey of cardiac pacing in the United States in 1989. AB - A survey of physicians who implant permanent cardiac pacemakers was conducted to identify practice patterns related to pacemaker-implantation frequency, hospital and implantation-facility characteristics, indications for pacing and pulse generator replacement, preferences regarding device types, pacing modes, follow up methods and frequency, and type and frequency of pacing-related complications. Questionnaires were sent to 11,414 potential physician respondents and 6 pacemaker manufacturers. Implanters' opinions were solicited regarding such issues as the importance of various device features and capabilities, the appropriateness of practice guidelines, and the efficacy of quality-assurance measures. In 1989, 89,445 primary pacemaker implantations and 21,055 pulse generator replacements were performed by approximately 7,919 physicians at about 3,400 U.S. centers. Typically, a pacemaker manufacturer's sales representative played an active role in 80% of cases. Since the last survey, which examined pacing practices in 1985, primary implantations of dual-chamber pacemakers increased from 22 to 32%, and the proportion of adaptive-rate pacemakers increased from 1 to 40% of primary implants. The "typical" implanter used bipolar electrode systems in 90% of cases, single-chamber pacemakers in 70%, and the introducer method in 95% of lead placements. Significant differences in practice patterns were found among subsets of the survey respondents. Surgeons tended to work alone, use simpler, single-chamber pacemakers, and leave follow-up to others. Electrode stability tended to be better among implanters in nonacademic environments. The quadrennial survey continues to provide useful information on an easily identifiable and traceable patient population, but the process would be greatly simplified by the adoption of a "universal" reporting system such as that used in Europe. PMID- 1734645 TI - Role of sympathovagal interaction in diurnal variation of QT interval. AB - To elucidate the role of sympathovagal interaction in diurnal variation of QT interval, 24-hour ambulatory electrocardiographic recordings from 56 subjects (23 control subjects, 18 patients with atherosclerotic coronary artery disease, and 15 patients with diabetes mellitus) were studied. The QT interval at a heart rate of 60 beats/min (QT60) was determined for each of the day and night periods by regression analysis. Sympathetic and parasympathetic activities were assessed by spectral analysis of heart rate variability and represented by the low- and high frequency components, respectively. The proportion of high-frequency component to the sum of low- and high-frequency components was used as an index of sympathovagal balance. The relative increase in QT60 at night (delta QT60 [%]) was larger in control subjects (4.2 +/- 2.1%) than in patients with coronary artery disease (2.2 +/- 1.8%; p less than 0.01) and diabetes mellitus (-1.5 +/- 4.0%; p less than 0.001). When the data from the 3 subject groups were pooled and analyzed, delta QT60 was correlated with the change in the sympathovagal balance (r = 0.554; p less than 0.001). Low-frequency component in the day alone was also related with delta QT60 (r = 0.554; p less than 0.001), but the ratio or difference of the high-frequency component value between day and night was not. These results indicate that although change in sympathovagal balance was responsible for the diurnal variation in QT interval, the enhanced sympathetic activity in the day was a major determinant of this phenomenon. PMID- 1734646 TI - Circadian variation in ventricular arrhythmias in hypertensive men. AB - Circadian patterns have been observed for various cardiovascular functions and events including sudden cardiac death. This study examined whether ventricular arrhythmias could be a pathophysiologic explanation for the increase in prevalence of sudden cardiac death observed between 6 A.M. and noon. Hypertensive men 35 to 70 years of age and without a history of symptomatic cardiac disease were withdrawn from diuretic treatment and received 1 month of oral electrolyte repletion with both 40 mmol of potassium chloride and 400 mg of magnesium oxide daily. Then continuous 24-hour Holter monitoring was performed and ventricular arrhythmias were classified by 6-hour time intervals. The interval from 6 A.M. to noon revealed a higher prevalence of complex or frequent ventricular arrhythmias than the interval from midnight to 6 A.M., as well as a higher mean number of ventricular premature complexes per hour. The differences were statistically significant (p less than 0.01) and amounted to increases of about one third. Ventricular arrhythmias during the other two 6-hour periods were intermediary in frequency. It is concluded that the increase in sudden cardiac death noted in the morning might be related, at least in part, to an increase in frequency of ventricular arrhythmias; the implications of this observation for preventive cardiology deserve further investigation. PMID- 1734647 TI - Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation. AB - For comparable decreases in systemic resistance, angiotensin-converting enzyme inhibitors produce a lesser increase in cardiac output than do previously used vasodilators. Although the reason for this is not yet clear, the possibility of a negative inotropic effect of angiotensin-converting enzyme inhibitors was demonstrated by intracoronary injection. The effects of an oral dose of captopril on systolic performance were assessed by examining left ventricular (LV) pressure volume loops obtained with simultaneous cineangiography and micromanometer pressure recordings before and 90 minutes after administration of oral captopril (25 to 50 mg) in 18 patients with chronic, severe mitral regurgitation. Group 1 (n = 9) was given captopril alone, and group 2 (n = 9) was given captopril plus atropine (0.04 mg/kg intravenous) to assess the role of parasympathetic activity in mediating the effects of captopril. Captopril reduced heart rate (90 to 81 beats/min; p less than 0.002) and LV end-diastolic pressure (13 to 10 mm Hg; p = 0.03), despite a slight increase in end-diastolic volume (257 to 264 ml; p = not significant) that suggests improved diastolic properties. Despite a decrease in end-systolic pressure (103 to 90 mm Hg; p less than 0.001), ejection fraction did not increase (0.60 to 0.58; p = not significant) owing to an increase in end systolic volume (107 to 114 ml; p = 0.008). Contractile performance, estimated from the end-systolic pressure/volume quotient, was consistently depressed by captopril, as was the relation of preload-corrected ejection fraction to end systolic stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734648 TI - Comparison of results of percutaneous mitral valvuloplasty in patients with large (greater than 6 cm) versus those with smaller left atria. AB - To determine whether the presence of an aneurysmatic (severely enlarged) left atrium (greater than 60 mm on echocardiography) influences results of percutaneous mitral valvuloplasty (PMV), the clinical, echocardiographic and hemodynamic characteristics and the results of this technique were compared in 46 consecutive patients with aneurysmatic left atrium (group I) and 125 consecutive patients without such echocardiographic finding (group II). Left atrial size was 70.5 +/- 8 vs 50.1 +/- 6 mm (p less than 0.005) in groups I and II, respectively. Patients in group I were older (57 +/- 12 vs 48 +/- 12 years, p less than 0.025), more symptomatic (New York Heart Association functional class greater than or equal to III or IV: 67 vs 42%, p less than 0.05), and had atrial fibrillation more frequently (91 vs 44%, p less than 0.001). The echocardiographic score (8.9 +/- 1.9 vs 7.5 +/- 2, p less than 0.005) and the incidence of mild mitral regurgitation on angiography before PMV (54 vs 30%, p less than 0.01) was also higher in group I patients. Hemodynamic parameters before PMV were similar in both groups, but after the procedure, final mitral valve area (1.61 +/- 0.5 vs 1.95 +/- 0.4 cm2, p less than 0.05) and the absolute increase in mitral area (0.81 +/- 0.3 vs 1.02 +/- 0.3 cm2, p less than 0.05) were lower and mean pulmonary artery pressure (35 +/- 10 vs 28 +/- 9 mm Hg, p less than 0.025) was higher in group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734649 TI - Hemodynamic effects of nitroprusside on valvular aortic stenosis. AB - The effects of acute reduction of left ventricular (LV) loading in valvular aortic stenosis (AS) were examined. Thirty-five consecutive patients with AS (peak-to-peak aortic valve gradient 66 +/- 26 mm Hg, aortic valve area 0.65 +/- 0.22 cm2) were given intravenous sodium nitroprusside (1 to 3 micrograms/kg/min) to reduce systolic aortic pressures by greater than 10 mm Hg (mean aortic pressure 99 +/- 15 to 80 +/- 15 mm Hg; p less than 0.001). Overall, nitroprusside infusion resulted in little change in cardiac index (2.72 +/- 0.61 to 2.67 +/- 0.58 liters/min/m2; p = not significant). Individual patients had a range of responses. Fourteen patients (group 1) had an increase in cardiac index (2.42 +/- 0.59 to 2.74 +/- 0.67 liters/min/m2; p less than 0.001), whereas 21 (group 2) had a decrease or no change (2.93 +/- 0.56 to 2.61 +/- 0.52 liters/min/m2; p less than 0.001). Comparison of these subgroups showed that a cardiac index increase with nitroprusside was significantly predicted by a higher LV end-diastolic pressure (26 +/- 12 vs 15 +/- 6 mm Hg), lower LV ejection fraction (44 +/- 18 vs 62 +/- 12%). smaller aortic valve area (0.52 +/- 0.12 vs 0.74 +/- 0.22 cm2) and lower cardiac index (2.42 +/- 0.59 vs 2.93 +/- 0.56 liters/min/m2) (all values groups 1 and 2, respectively). It is concluded that there is a disparate response to acute vasodilatation in AS. Potentially beneficial effects are seen in a subgroup of patients, especially those with increased filling pressures and impaired LV function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734650 TI - Value of exercise Doppler echocardiography in patients with prosthetic or bioprosthetic cardiac valves. AB - Doppler echocardiographic evaluation of the prosthetic valve function is usually performed at rest, although this situation is not representative for patients' daily activities. Therefore, a symptom-limited Master 2-step test was performed in 61 asymptomatic patients with normal left ventricular function. No adequate Doppler signals were obtained in 5 of 61 patients (8%) within 60 second after termination of exercise. In patients with aortic valve prostheses (n = 24), heart rate increased from 74 +/- 10 to 105 +/- 18 beats/min, the maximal instantaneous gradient from 44 (range 22 to 90) to 68 (range 28 to 165) mm Hg (r = 0.89) and the mean gradient from 24 (range 12 to 50) to 39 (range 18 to 100) mm Hg (r = 0.90). In 6 of 11 patients with a maximal flow velocity ratio between the left ventricular outflow tract and the aortic valve prosthesis less than or equal to 0.25, the mean gradient increased to a value greater than or equal to 50 mm Hg after exercise, whereas in patients with a ratio of greater than or equal to 0.25, this never occurred. In patients with mitral valve prostheses (n = 39), heart rate increased from 80 +/- 12 to 116 +/- 14 beats/min and mean gradient from 6 (range 3 to 10) to 14 (range 6 to 25) mm Hg (r = 0.59). The correlation of the mean diastolic pressure gradient after exercise with pressure half-time was 0.66. Systolic pulmonary artery pressure at rest and after exercise could be determined in 22 of 39 patients (56%) and increased from 34 (range 20 to 70) to 57 (range 35 to 110) mm Hg. It is concluded that the response to exercise can, to a large extent, be inferred from Doppler parameters at rest, particularly in patients with aortic valve prostheses. The clinical implication of the high gradients found in some asymptomatic patients in the present study should be elucidated by follow-up studies. PMID- 1734651 TI - Influence of mitral regurgitation on the response to captopril therapy for congestive heart failure caused by idiopathic dilated cardiomyopathy. AB - To assess the influence of mitral regurgitation (MR) on the response to captopril therapy for congestive heart failure (CHF), 30 patients with idiopathic dilated cardiomyopathy in New York Heart Association functional class III were studied. Left ventricular end-diastolic diameter and stroke volume were measured by Doppler echocardiography, and exercise tolerance by exercise testing before and at 1, 3 and 12 months after treatment. Patients were classified into 2 groups: those with (n = 14) and those without (n = 16) MR. No significant differences were observed between the 2 groups in pretreatment studies. Exercise tolerance increased significantly in the group with MR (p less than 0.001) during the year of follow-up, from 514 +/- 193 seconds at baseline study to 671 +/- 178 seconds (p less than 0.0005) at 1 month, 688 +/- 127 seconds (p less than 0.0005) at 3 months and 690 +/- 108 seconds (p less than 0.01) at 12 months. The group without MR had no significant changes. Stroke volume increased significantly only in the MR group during follow-up (p less than 0.01), changing from 43 +/- 9 ml at baseline study to 52 +/- 11 ml (p less than 0.01) at 1 and 49 +/- 11 ml (p less than 0.01) at 3 months. At 12 months the increase was not statistically significant. Left ventricular end-diastolic diameter decreased more in the group with than without MR, although the differences were not significant. Thus, the presence of dynamic MR appears to be an important factor in the therapeutic response to captopril therapy for CHF. PMID- 1734652 TI - Predictors of long-term survival with Ebstein's anomaly of the tricuspid valve. AB - In patients with Ebstein's anomaly of the tricuspid valve, predictors of death and indications for surgery are poorly defined. We retrospectively reviewed 48 patients with Ebstein's anomaly, 17 (35%) of whom presented in the first week of life. Duration of follow-up extended to 32 years (greater than 10 years in 35%). Twenty of the 48 patients (42%) died, 6 in the first week of life and 1 at age 5 months. Thirteen of the 41 patients surviving to age 6 months subsequently died, 50% probability of survival being reached at 47 years. Significant (p less than or equal to 0.05) predictors of death in this group were: male sex, cardiothoracic ratio greater than or equal to 0.65, New York Heart Association class III or IV, breathlessness and the absence of Wolff-Parkinson-White syndrome. Eight patients died suddenly. A cardiothoracic ratio greater than or equal to 0.65 was a better predictor of sudden death than functional status. All who developed atrial fibrillation died within 5 years. Other atrial arrhythmias were not helpful in predicting sudden death. In view of these findings, tricuspid valve surgery is recommended before the cardiothoracic ratio reaches 0.65, regardless of the symptomatic state. PMID- 1734653 TI - Differences in circadian blood pressure between upper and lower extremity in aortic coarctation patients with and without postoperative pressure gradients. AB - The purpose of this study was to investigate possible circulatory differences between pre- and poststenotic vascular beds in postoperative coarctation patients with and without a residual pressure gradient during a physiologic decrease in circulatory activity. Simultaneous diurnal variations in blood pressure in the brachial and femoral arteries were recorded in 5 long-term postoperative coarctation patients with and in 5 without a pressure gradient. The patients were studied 6.5 to 8.5 years postoperatively with intraarterial blood pressure telemetry. Both groups of patients had a normal pressure decrease during the hours of sleep. A significant (p less than 0.05) increase, however, in brachial to femoral pressure gradients developed during the hours of sleep in patients with a positive gradient in contrast to patients without a gradient who had identical pressure profiles in both vascular beds. A significant positive correlation was found between changes in mean pressure gradient and upper extremity systolic pressure (r = 0.79, p less than 0.01). There was no difference between the 2 groups regarding pre- and postoperative pressures, preoperative gradients or age at surgery. Results suggest that normalization of prestenotic circadian vascular reactivity depends on complete relief of the gradient, and that upper extremity vascular abnormality may not be fully irreversible, even in older patients with coarctation. PMID- 1734654 TI - Systemic venous flow during cardiac surgery examined by intraoperative transesophageal echocardiography. AB - Patterns of systemic venous return change after cardiac surgery. However, the exact timing and underlying mechanisms are not well understood. To analyze these changes transesophageal echocardiography was used to evaluate 21 patients (mean age 56 +/- 17 years) during cardiac surgery. Eleven patients underwent coronary bypass grafting, 2 had ablation of accessory bundles, 4 had mitral and 4 had aortic valve replacements. All were in sinus rhythm and were undergoing their first cardiac operation. Hepatic and pulmonary venous flow, tricuspid annular motion, and signs of tricuspid regurgitation were recorded sequentially 5 times: (A) with chest closed, (B) with chest open and pericardium closed, (C) with both chest and pericardium open, (D) after cardiopulmonary bypass with chest open, and (E) after cardiopulmonary bypass with chest closed. The hepatic venous Doppler flow velocity integrals (cm) changed, from stage A to stage E: systolic flow decreased from 5.9 +/- 5.2 to 2.2 +/- 1.4 (p less than 0.01); diastolic flow increased from 3.1 +/- 1.5 to 4.8 +/- 3.3 (p less than 0.001); and systolic to diastolic ratio decreased from 2.0 +/- 1.2 to 0.7 +/- 0.6 (p less than 0.001). Reversed flow at the end of ventricular systole was present in 9 patients (43%) at stage A and in all patients at stage E. Decreased tricuspid annular motion was noted in all but 1 patient after cardiopulmonary bypass. No patient presented significant tricuspid regurgitation at any stage. In conclusion, the significant change in the pattern of systemic venous return after open heart surgery is not due to opening of the chest wall or parietal pericardium, or to tricuspid regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734655 TI - Relation of plain chest radiographic findings to pulmonary arterial pressure and arterial blood oxygen levels in patients with acute pulmonary embolism. AB - Abnormalities of the plain chest radiograph of 123 patients with acute pulmonary embolism (PE) and no prior cardiac or pulmonary disease were related to the pulmonary arterial mean pressure, the partial pressure of oxygen in arterial blood, and the alveolar-arterial oxygen gradient. Patients with either a prominent central pulmonary artery or cardiomegaly had higher pulmonary arterial mean pressures than did patients with atelectasis, a pulmonary parenchymal abnormality or pleural effusion (p less than 0.001). These radiographic findings give clues to the severity of pulmonary hypertension in acute PE and suggest that pulmonary infarction or hemorrhage is associated with less severe PE. PMID- 1734656 TI - Rate-corrected mean velocity of fiber shortening-stress at peak systole as a load independent measure of contractility. AB - The relation of mean velocity of fiber shortening-stress at end-systole is a good load-independent index of left ventricular contractility, but involves simultaneous M-mode echocardiography, carotid tracing and blood pressure determination, which may be impractical in children. As stress at peak systole and end-systole are closely related, this study examined whether the relation of mean velocity of fiber shortening-stress at peak systole could be used as a simpler method of assessing left ventricular contractility in a normal population of children. In addition, the cross-sectional normal range for a pediatric population was obtained. In 25 normal children aged 4 to 17 years (mean age 11), rate-corrected mean velocity of fiber shortening (MVCFc), stress at peak systole (sigma PS), and end-systolic stress (sigma ES) were determined using echocardiography, carotid pulse tracing and blood pressure measurement. Six patients with cardiomyopathy (mean age 8 years) were also studied. The relation of stress at peak systole and end-systolic stress was sigma PS = 1.004 sigma ES + 12.0 (r = 0.91, SEE = 4.98; p less than 0.001) for the normal group, and sigma PS = 1.083 sigma ES + 7.7 (r = 0.99, SEE = 4.07; p less than .001) for the cardiomyopathic group. This slope of the regression line was slightly higher and the difference was statistically significant. The slope of MVCFc = 0.0066 sigma PS + 1.55 (SEE = 0.131, r = -0.52) was nearly identical to that of MVCFc = 0.0065 sigma ES + 1.46, (SEE = 0.135, r = -0.46), with no difference in the regression coefficients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734657 TI - Consequences of a media campaign focusing on delay in acute myocardial infarction. PMID- 1734658 TI - Interobserver variability in grading of coronary arterial narrowings using the American College of Cardiology/American Heart Association grading criteria. PMID- 1734659 TI - Lack of correlation between the signal-averaged electrocardiogram and regional wall motion abnormalities in coronary artery disease. PMID- 1734660 TI - Efficacy and safety of a new selective class III antiarrhythmic agent dofetilide in paroxysmal atrial fibrillation or atrial flutter. PMID- 1734661 TI - Usefulness of transesophageal echocardiography for diagnosis of mitral valve prolapse. PMID- 1734662 TI - Efficiency of disopyramide in hypertrophic cardiomyopathy during stress states. PMID- 1734663 TI - Assessment of relative sensitivities of noninvasive tests for cardiac amyloidosis in documented cardiac amyloidosis. PMID- 1734664 TI - Simultaneous mechanical clot fragmentation and pharmacologic thrombolysis in acute massive pulmonary embolism. PMID- 1734665 TI - Patency of ductus arteriosus in pulmonary atresia and ventricular septal defect. PMID- 1734666 TI - The bedside Valsalva maneuver in the diagnosis of congestive heart failure. PMID- 1734667 TI - Doctors, save your money because there will be less in the future. PMID- 1734668 TI - Rayon balls and disposable-diaper material selectively adsorb creatinine. AB - One method for the collection of urine samples from infants involves absorption of the urine on cotton balls placed in the diaper. Such samples are not timed and excretions are often expressed per mg of urinary creatinine. An assumption in this method is that the creatinine concentration is not changed by the absorption process. The concentration of creatinine in urine samples was measured before and after absorption of the urine by cotton balls, rayon balls, or diaper material over a range of wetness. For urine from both adults and infants, absorption on rayon balls and diaper material caused an important artifactual decrease in the concentration of creatinine. The effect was particularly striking in lightly wetted samples; the mean percent decrease was only 3 +/- 2% for cotton but was 9 +/- 5% for rayon (n = 10) and 13 +/- 4% for diaper material (n = 7). These data provide evidence that rayon balls and diaper material (and to a lesser extent cotton balls) selectively adsorb creatinine from human urine. PMID- 1734669 TI - Caloric, but not macronutrient, compensation by humans for required-eating occasions with meals and snack varying in fat and carbohydrate. AB - Six subjects participated in a residential study assessing the effects of covert macronutrient and energy manipulations during three required-eating occasions (breakfast, lunch, and afternoon snack) on total macronutrient and energy intakes. Overall, energy content of the occasions varied between approximately 3000 and approximately 7000 kJ (approximately 700 and approximately 1700 kcal) with the majority of the differential derived from either fat or carbohydrate (CHO). Each condition (high, medium, and low fat; high, medium, and low CHO; and no required eating) was examined for 2 d. Subjects compensated for the energy content of the required occasions such that only under the low-CHO condition (11,297 +/- 3314 kJ) was total daily energy intake lower than that observed in the absence of required occasions (13,297 +/- 1356 kJ). Only total energy intake under the high-fat condition (12,326 +/- 2548 kJ) was significantly different from its matched CHO condition (high-CHO condition: 14,665 +/- 2686 kJ). In contrast to the clear evidence for caloric compensation, there were no differential effects of condition on macronutrient intake, ie, there was no macronutrient compensation. PMID- 1734670 TI - Food intake measured by an automated food-selection system: relationship to energy expenditure. AB - Measuring food intake in a laboratory usually involves limited food choices. An automated food-selection system with two vending machines containing a large variety of foods was used to measure food intake in 10 male volunteers (31 +/- 6 y, 69.2 +/- 7.1 kg, 18 +/- 7% fat, mean +/- SD) on a metabolic ward. The effect of carbohydrate, fat, and protein intakes on 24-h energy expenditure (24EE) and substrate oxidations was measured in a respiratory chamber during day 4 of weight maintenance and day 7 of ad libitum intake. Ad libitum intake resulted in a 7-d overfeeding of 6468 +/- 3824 kJ/d above weight-maintenance requirements, leading to a 2.3 +/- 1.2-kg gain. The 10,975 +/- 3774 kJ excess energy intake on day 7 of ad libitum intake caused a 1205 +/- 920 kJ/d increase in 24EE (delta 24EE = 0.17 x delta intake - 695; r = 0.71, P less than 0.02). Of the excess carbohydrate intake, 74% was oxidized (r = 0.86, P less than 0.001), whereas excess fat intake was not. Carbohydrate and protein stores are regulated whereas excess fat intake is channeled to fat stores. PMID- 1734671 TI - Energy intake required to maintain body weight is not affected by wide variation in diet composition. AB - Diets rich in fat may promote obesity by leading to a greater deposition of adipose-tissue triglycerides than do isoenergetic diets with less fat. This possibility was examined by a retrospective analysis of the energy needs of 16 human subjects (13 adults, 3 children) fed liquid diets of precisely known composition with widely varied fat content, for 15-56 d (33 +/- 2 d, mean +/- SE). Subjects lived in a metabolic ward and received fluid formulas with different fat and carbohydrate content, physical activity was kept constant, and precise data were available on energy intake and daily body weight. Isoenergetic formulas contained various percentages of carbohydrate as cerelose (low, 15%; intermediate, 40% or 45%; high, 75%, 80%, or 85%), a constant 15% of energy as protein (as milk protein), and the balance of energy as fat (as corn oil). Even with extreme changes in the fat-carbohydrate ratio (fat energy varied from 0% to 70% of total intake), there was no detectable evidence of significant variation in energy need as a function of percentage fat intake. PMID- 1734672 TI - Effects of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity in obese individuals. AB - To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity we studied 12 obese subjects (body mass index 33.4 +/- 1.1) before and after 6 wk of a very-low-calorie diet (VLCD) with euglycemic insulin clamp in combination with indirect calorimetry. Body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001) and fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001). Total glucose disposal during insulin clamp increased from 30.4 +/- 4.3 to 38.4 +/- 4.4 mumol.kg lean body mass (LBM)-1.min-1 (P less than 0.05), insulin-stimulated glucose oxidation from 14.3 +/- 4.6 to 19.1 +/- 1.4 mumol.kg LBM-1.min-1 (P less than 0.05), and non oxidative glucose metabolism from 16.0 +/- 3.8 to 19.3 +/- 3.6 mumol.kg LBM-1.min 1 (NS). Lipid oxidation decreased in the basal state (P less than 0.05) and during the insulin clamp (P less than 0.01). The basal rate of energy expenditure decreased from 99.1 +/- 4.6 to 88.5 +/- 2.7 kJ.kg LBM-1.min-1 (P less than 0.05) after weight reduction. A reduction in fat mass achieved by VLCD is associated with reduced lipid oxidation and, because of substrate competition, enhanced glucose oxidation. The physiological consequence is improved insulin sensitivity. PMID- 1734673 TI - Relationship of perceived macronutrient and caloric content to affective cognitions about food in eating-disordered, restrained, and unrestrained subjects. AB - Cognitive sets concerning food were examined in eating-disorder patients and in restrained and unrestrained control subjects. Subjects rated 38 common foods for preference, presence or absence of guilt and danger, preferred monthly frequency, and caloric, fat, and carbohydrate content. Cognitive ratings were examined based upon the individual's perceived amounts of calories and macronutrients. Hedonic ratings of foods perceived as high in fat or calories were different in patients with current or past anorexia and did not change with treatment. The fat-calorie aversions seen in these patients, therefore, appear to be stable trait characteristics of the disorder. Guilt and danger were perceived as separate constructs by unrestrained and restrained control subjects but not by patients. Perceived high amounts of calories or fat triggered stronger feelings of guilt and danger for restrained control subjects and patients (especially bulimic patients) as compared with unrestrained control subjects. The patients' expressions of guilt and danger improved with treatment. PMID- 1734674 TI - Laboratory assessment of feeding behavior in bulimia nervosa and healthy women: methods for developing a human-feeding laboratory. AB - We have designed a human-feeding laboratory to be used to study feeding behavior in patients with eating disorders. Twenty-one normal-weight bulimic subjects consumed 29.711 +/- 39.940 MJ (range 0.862-178.632 MJ; 7101 +/- 9546 kcal, range 206 to 42,694 kcal) in 24 h. In comparison, 11 healthy volunteer women, when instructed to eat ad lib for 48 h, ate 7.715 +/- 2.590 MJ (1844 +/- 619 kcal) during the first 24 h and 7665 +/- 1828 MJ (1832 +/- 437 kcal) during the second 24 h. Bulimics and control subjects had a similar number of eating intervals (6.6 +/- 2.6 vs 5.0 +/- 1.7); 72% of the bulimic subjects' meals were similar in size to the meals of the controls [167-4100 kJ (40-980 kcal)] but these meals were higher in carbohydrate and lower in fat in bulemic patients. Excessive caloric intake by bulimic subjects was because 28% of their meals were very large [range 4.427-28.150 MJ (1058-6728 kcal)]. Data gathered in a laboratory setting appears to be a reasonable replication of naturalistic feeding and suggest that such a laboratory may prove useful for future studies of feeding behaviors in humans. PMID- 1734675 TI - Insulin-like growth factor I and low-density-lipoprotein cholesterol in women during high- and low-fat feeding. AB - In vitro studies suggest that insulin-like growth factor I (IGF-I) may modulate hepatic production and peripheral utilization of lipoproteins. We measured blood concentrations of IGF-I; total, high-density-lipoprotein, and low-density lipoprotein (LDL) cholesterol; and apolipoproteins in 18 women with above average cholesterol after high- and low-fat diet periods. Total cholesterol fell 6% (P less than 0.02) during the low-fat diet because of reduced concentrations of LDL cholesterol (P less than 0.01). Serum concentrations of IGF-I were inversely correlated with total and LDL cholesterol and apolipoprotein B during both high fat (r = -0.676, P less than 0.005; r = -0.745, P less than 0.001; and r = 0.504, P less than 0.04, respectively) and low-fat (r = -0.656, P less than 0.005; r = -0.757, P less than 0.001; and r = -0.695, P less than 0.001, respectively) diets. IGF-I increased with reduced fat intake in obese subjects only. Thus, IGF-I may contribute to the regulation of LDL cholesterol in mildly hypercholesterolemic women but may not mediate the beneficial response to reduced fat intake. PMID- 1734676 TI - Differential reduction of plasma cholesterol by the American Heart Association Phase 3 Diet in moderately hypercholesterolemic, premenopausal women with different body mass indexes. AB - The ability of a low-fat, low-cholesterol diet to improve the risk-factor profiles of moderately hypercholesterolemic, premenopausal women was evaluated. Nineteen women were fed a typical American diet for 1 mo, after which a low-fat diet consisting of 21% of total energy (en%) as fat, 59 en% carbohydrates, 19 en% protein, and 96 mg cholesterol/d (P:S 1.8) was given. After 5 months, total and low-density lipoprotein (LDL) cholesterol was decreased by 7% and 11%, respectively, and total triglycerides increased by approximately 30%. High density-lipoprotein (HDL) cholesterol was decreased by 12% at month 2 and 5% at month 5 (P less than 0.05). Although HDL2 cholesterol decreased progressively throughout the diet period to -35% by month 5, HDL3 cholesterol, which decreased to -5% at month 1, increased to +7% by month 5. Of the plasma apolipoproteins only apo A-II was altered (+15%) by the diet. Body mass index correlated to baseline values and affected response to diet; only the leanest women had significant decreases in total, LDL, and HDL2 cholesterol in response to the low fat diet. PMID- 1734677 TI - Egg intake does not change plasma lipoprotein and coagulation profiles. AB - The effect of the intake of 3-14 eggs/wk on biochemical risk markers of coronary heart disease (CHD) was examined in 70 young men who followed a high-fat diet. The study consisted of a run-in phase during which all subjects ate 3 eggs/wk for 2 mo and an experimental phase during which a reference group continued eating 3 eggs/wk and two experimental groups ate either 7 or 14 eggs/wk for 5 mo. The mean coefficients of variation in total plasma cholesterol (5.4-7.4%) were similar in all three groups and were larger than the mean changes of 0.2-5.6% in plasma cholesterol from baseline to end in the experimental groups. Except for increased lecithin-cholesterol acyltransferase activities and total serum protein concentrations, no significant differences in lipoproteins or coagulation factors occurred between groups. It seems that egg intake in this range did not influence CHD risk markers in these subjects. Recommendations to lower risk should probably concentrate on a reduction in fat and not cholesterol intake. PMID- 1734678 TI - Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding. AB - In this paper we compare the fatty acid content of egg yolks from hens fed four different feeds as a source of docosahexaenoic acid to supplement infant formula. Greek eggs contain more docosahexaenoic acid (DHA, 22:6 omega 3) and less linoleic acid (LA, 18:2 omega 6) and alpha-linolenic acid (LNA, 18:3 omega 3) than do fish-meal or flax eggs. Two to three grams of Greek egg yolk may provide an adequate amount of DHA and arachidonic acid for a preterm neonate. Mean intake of breast milk at age 1 mo provides 250 mg long-chain omega 3 fatty acids. This amount can be obtained from less than 1 yolk of a Greek egg (0.94), greater than 1 yolk of flax eggs (1.6) and fish-meal eggs (1.4), or 8.3 yolks of supermarket eggs. With proper manipulation of the hens' diets, eggs could be produced with fatty acid composition similar to that of Greek eggs. PMID- 1734679 TI - Mycoprotein reduces blood lipids in free-living subjects. AB - Mycoprotein is a food produced by continuous fermentation of Fusarium graminearum (Schwabe). A previous metabolic study showed that mycoprotein decreased total and low-density-lipoprotein (LDL) cholesterol and increased high-density-lipoprotein (HDL) cholesterol. This study was undertaken to determine the effects of mycoprotein under free-living conditions. Two groups of subjects with slightly raised cholesterol concentrations participated in the 8-wk study. The experimental group was fed cookies containing mycoprotein and the control group was fed a nutrient-balanced cookie without mycoprotein. After 8 wk of treatment total cholesterol was reduced by 0.46 mmol/L in the control group and 0.95 mmol/L in the mycoprotein group, and LDL was reduced by 0.34 mmol/L in the control group and 0.84 mmol/L in the mycoprotein group. All analysis of variance differences were statistically significant. This study confirms the metabolic-study results and we are now relatively confident that mycoprotein exerts a beneficial effect on blood lipids. PMID- 1734680 TI - Bioavailability of starch in various wheat-based bread products: evaluation of metabolic responses in healthy subjects and rate and extent of in vitro starch digestion. AB - Glucose and insulin responses to bread products were evaluated in healthy subjects. Also studied were the rate of in vitro starch digestion and the content of in vitro resistant starch (RS). Three white-wheat-bread (WWB) products varying in crust-crumb ratio and monoglyceride addition, three bread products with a high soluble fiber content (HSFB), and two coarse-wheat breads (CB) were included. The metabolic responses to WWBs were in general higher than those to CB and HSFB products. The most prominent reduction in metabolic responses was noted with the CBs with intact kernels and the HSFBs with oat bran. The starch in these products was also more slowly released from a dialysis tubing after enzyme incubation of chewed samples. The RS content ranged from 0 to 1.7 g/100 g starch. HSFBs and the CB with intact kernels showed a higher satiety score than did the WWBs immediately after the test meal. PMID- 1734681 TI - 13C appearance in plasma glucose and breath CO2 during feeding with naturally 13C enriched starchy food in normal humans. AB - We have used a recently developed technique (isotope-ratio mass spectrometer) to measure 13C appearance in plasma glucose and breath CO2 in eight normal subjects during feeding with naturally 13C-enriched starch. 13C in CO2 and plasma glucose, metabolites and insulin concentrations, carbohydrates, and lipid oxidation were measured after ingestion of 76 g glucose equivalent of crackers, pasta, or polenta. 13C in plasma glucose displays a very different pattern from plasma glucose concentration. It increases steadily for 90 min before reaching a plateau for approximately 2 h and slowly declines during the last 2 h of the study. No significant difference was observed with the three different starchy foods tested although plasma glucose tended to be higher during feeding with polenta. In summary measurement of 13C in plasma glucose during feeding with naturally 13C labeled carbohydrates yields new insight in the study of carbohydrate bioavailability in humans. PMID- 1734682 TI - Effects of timing and dose of vitamin A on tissue retinol concentrations and antibody production in the previously vitamin A-depleted rats. AB - The effect of retinol repletion in previously vitamin A-depleted Lewis rats on antibody production to pneumococcal polysaccharide (SSS-III) was studied. When vitamin A-depleted rats were given either 0.35 mumol (0.1 mg) or 5.2 mumol (1.5 mg) retinol, plasma retinol became normal within 8 h. Liver and lymphoid-organ retinol concentrations were normalized by 1 d after repletion with 5.2 mumol but not 0.35 mumol retinol. Antibody production to SSS-III was compared after administering 5.2 mumol retinol either as a divided dose (half given 4 d before and half given on the day of immunization) or as a single dose concurrent with immunization. Vitamin A-depleted rats produced very little SSS-III-specific antibody. The divided dose of retinol consistently restored anti-SSS-III production whereas the single concurrent dose was less effective despite equal effects on tissue retinol concentrations. Interestingly, normalization of plasma retinol was not always a good predictor of the immune response to pneumococcal polysaccharide. PMID- 1734683 TI - Extrinsic vs intrinsic labeling of the calcium in whole-wheat flour. AB - Fractional absorption of calcium from bread made either from intrinsically or extrinsically labeled whole-wheat flour was compared in 11 healthy adult women. The intrinsic label was provided by 45Ca injected individually into stems of wheat plants during growth. The extrinsic tag was introduced by adding 45Ca to unlabeled flour via the water used in dough making. The two labeled breads were tested in a randomized crossover design using a standardized breakfast administered after an overnight fast. Approximately 80 g labeled bread was consumed by each subject, providing a total calcium load of 13.3 mg. Fractional absorption from the intrinsically labeled bread averaged 0.812 +/- 0.130 (mean +/ SE) and from the extrinsically labeled bread 0.792 +/- 0.113. The mean difference, within subject, was only 0.025 +/- 0.016 and was not significantly different from zero. Extrinsic labeling of the calcium of whole-wheat flour results in a degree of labeling homogeneity equivalent to that of intrinsic labeling, at least for a leavened bread product. PMID- 1734684 TI - Resting energy expenditure, caloric intake, and short-term weight change in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. AB - To assess the causes of short-term weight loss in patients with acquired immunodeficiency syndrome (AIDS), we measured resting energy expenditure (REE), caloric intake, and the 28-d weight trend in control subjects, human immunodeficiency virus (HIV)+ subjects, AIDS patients, and AIDS patients during secondary infection (AIDS-SI). REE was increased in HIV+ (11%), AIDS (25%), and AIDS-SI (29%). Caloric intake was similar in control subjects, HIV+, and AIDS but reduced 36% in AIDS-SI, who consumed 17% fewer calories than their REE. Average short-term weight was stable for HIV+ and AIDS but decreased 5% in AIDS-SI. Weight trend correlated with caloric intake but not with REE. Thus HIV+ and AIDS are able to partially compensate for increased REE because they do not show short term weight loss. Decreased caloric intake is critical for short-term weight loss and is seen during secondary infection. Inability of decreased caloric intake to decrease REE during infection accelerates short-term weight loss. Rapid weight loss with anorexia may be a harbinger of secondary infection in AIDS. PMID- 1734685 TI - Metabolic advantages of spreading the nutrient load: effects of increased meal frequency in non-insulin-dependent diabetes. AB - The acute effect of increasing meal frequency as a model of slow absorption was studied for 1 d in 11 patients with non-insulin-dependent diabetes. On 1 d they took 13 snacks (the nibbling diet) and on another day the same diet was taken as three meals and one snack (the three-meal diet). The nibbling diet reduced mean blood glucose, serum insulin, and C peptide concentrations over the 9.5 h of observation and 24-h urinary C peptide output by 12.7 +/- 3.7% (mean +/- SE) (P = 0.0062), 20.1 +/- 5.8% (P = 0.0108), 9.2 +/- 2.6% (P = 0.0073), and 20.37 +/- 8.12% (P = 0.039), respectively, compared with the three-meal diet. Serum triglyceride concentrations were lower by 8.5 +/- 3.2% (P = 0.037). Despite lower insulin concentrations on the nibbling diet, the concentrations of free fatty acids, 3-hydroxybutyrate, and the insulin-sensitive branched-chain amino acids responded similarly on both treatments. Metabolic benefits seen with increased meal frequency may explain the success of similar agents that prolong absorption, including fiber and enzyme inhibitors. PMID- 1734686 TI - Fat elimination in acute renal failure: long-chain vs medium-chain triglycerides. AB - Elimination and hydrolysis of fat emulsions containing long-chain (LCT; Intralipid) or long- and medium-chain triglycerides (MCT; Lipofundin MCT) were compared in seven patients with acute renal failure (ARF) and six healthy control subjects. In control subjects, clearance of MCT was slightly higher than that of LCT (1.93 +/- 0.34 vs 1.55 +/- 0.3 mL.kg body wt-1.min-1, P less than 0.05). The rise in plasma triglycerides was similar and the release of free fatty acids was higher during MCT (P less than 0.02). In ARF, clearance of both LCT and MCT was equally reduced (0.53 +/- 0.12 vs 0.59 +/- 0.14 mL.kg body wt-1.min-1, P less than 0.01 vs control subjects). Again, the rise in triglycerides was comparable. Free fatty acid release was higher during MCT but lower than in control subjects. Plasma concentrations of glucose and lactate were not affected in control subjects but increased during both LCT and MCT in ARF. Thus elimination of both LCT and MCT is profoundly decreased in ARF. The impaired lipolysis in ARF cannot be circumvented by the use of MCT. PMID- 1734687 TI - The analysis of stable isotopes in urine to determine the fractional absorption of zinc. AB - We measured isotopic enrichment in urine after oral and intravenous administration of stable isotopes of zinc to determine fractional absorption (FA). 68Zn and 70Zn were administered orally and intravenously to four normal adults. Subsequently, urine and fecal samples were collected for 7 and 14 d, respectively, ashed, and passed through ion-exchange columns to separate zinc from other elements. Samples were analyzed by fast-atom-bombardment mass spectrometry. From 32 h onwards the enrichment of 68Zn and 70Zn in urine declined proportionately so that FA could be determined as follows: FA = enrichment (oral/iv) x dose (iv/oral). FA determinations from urine and feces (cumulative excretion) were, respectively, for subject ZK1, urine 0.79 +/- 0.03 and feces 0.70 +/- 0.01; ZK2, 0.79 +/- 0.05 and 0.69 +/- 0.02; ZK3, 0.26 +/- 0.01 and 0.25 +/- 0.01; and ZK4, 0.41 +/- 0.02 and 0.37 +/- 0.02. ZK1 and ZK2 received the oral isotope while fasting whereas ZK3 and ZK4 received the oral isotope with meals. FA of zinc can be determined by measurement of isotope enrichment in urine. PMID- 1734688 TI - Phytate and colon-cancer risk. PMID- 1734689 TI - The case of the missing calories revisited. PMID- 1734690 TI - Urea kinetics and total parenteral nutrition. PMID- 1734691 TI - New weight guidelines for Americans. PMID- 1734692 TI - Aluminum and TPN-related bone disease. PMID- 1734693 TI - Management of perforation of the colon at colonoscopy. AB - We propose guidelines for the management of perforation of the colon at colonoscopy based upon a comprehensive literature review. Conservative management is advocated for silent perforations and in patients with mild or localized symptoms and signs diagnosed within 4-8 h of injury. Perforations diagnosed late may be managed by nonoperative methods, if the infection is confined as determined clinically or by imaging techniques. A suspected large perforation, generalized peritonitis, or failure to improve on conservative management will mandate surgical exploration. In an intermediate group of patients, decisions regarding management will depend on crucial information regarding the circumstances surrounding the procedure. These include the endoscopist's assessment of the size, mechanism, and timing of the perforation, the adequacy of bowel preparation, delay time to diagnosis, overall condition of the patient, and the presence or absence of associated colonic pathology. Antibiotic therapy should be given to all patients immediately upon diagnosis. Single-agent therapy with cefoxitin can be used in the immunocompetent patient. Under other circumstances, combination antibiotic treatment is indicated. PMID- 1734694 TI - Prospective randomized comparison of sodium tetradecyl sulfate and polidocanol as variceal sclerosing agents. AB - A prospective randomized controlled study was designed to evaluate differences in efficacy and complication rate between the two most commonly used sclerosing agents, sodium tetradecyl sulfate (STD) and polidocanol. Of 52 patients with esophageal variceal bleeding, 26 were randomized to receive sclerotherapy with 1.5% STD and 26 to receive 1% polidocanol at weekly intervals. Eradication of varices was achieved in 88% patients each of the STD and polidocanol group. There was no significant difference between patients injected with STD and polidocanol with regard to re-bleeding (27% vs. 15%) and mortality (11.5% in both). The use of STD, in contrast to polidocanol, was associated with a higher incidence of complications in terms of severe retrosternal pain (27% vs. 4%), deep ulceration (53% vs. 23%), dysphagia (88% vs. 46%), and stricture formation (27% vs. 8%). It was concluded that these two agents were similar in efficacy. However, polidocanol was superior due to a lower incidence of complications. PMID- 1734695 TI - Manometric characteristics in idiopathic and reflux-associated esophageal spasm. AB - Ancillary manometric findings, e.g., high amplitude contractions, repetitiveness, or elevated lower esophageal sphincter (LES) pressure, have been reported in diffuse esophageal spasm (DES). However, two recent changes in DES have been noted: 1) it has been redefined as increased simultaneous contractions, with intermittent peristalsis, and 2) there has been more attention to reflux associated DES. Therefore, our aims were to characterize the ancillary findings in currently defined DES and to determine whether these occurred in both idiopathic and reflux-associated DES. Records of 31 patients with DES (greater than 25% simultaneous contractions) were reviewed. Independent of manometry, some patients could be subclassified as idiopathic (N = 7; no heartburn; normal endoscopy or acid perfusion test) or reflux-associated (N = 10; heartburn; positive endoscopy). Both low and high LES pressures and contraction amplitudes were seen. Repetitive contractions were seen in nearly all patients, and segmental aperistalsis, dropped waves, or distally nonpropagated waves were seen in more than half. These findings were generally observed in both types of DES. This study of DES 1) confirms the high prevalence of repetitive contractions, 2) deemphasizes high LES pressure and contraction amplitude, 3) extends the findings to include other types of peristaltic dysfunction, and 4) indicates that manometric findings per se do not allow clear differentiation of idiopathic from reflux-associated DES. PMID- 1734696 TI - Reversal of negative pressure ventilation-induced lower esophageal sphincter dysfunction with metoclopramide. AB - We have previously demonstrated that lower esophageal sphincter (LES) dysfunction is induced in healthy volunteers placed in negative pressure body ventilators. This is important, because regurgitation of gastric contents and peptic esophagitis are frequent complications of the use of such ventilators. The present study was conducted to determine whether LES dysfunction during the use of these ventilators also occurs in patients with chronic respiratory failure, and whether this dysfunction can be pharmacologically reversed. Seven patients with documented chronic respiratory failure due to COPD were studied. After an overnight fast, esophageal, LES, and gastric pressures were simultaneously recorded in the unassisted state and during mechanically assisted ventilation, after which 10 mg iv metoclopramide were administered to each patient, and pressure recordings were continued for 1 h more. In all seven patients, baseline LES pressures were in the normal range. During the inspiratory cycle of mechanical ventilation, five of the seven patients demonstrated a significant reduction in LES pressure, whereas it was unchanged in the other two. Within 15 min of metoclopramide administration, there was an increase in LES pressure to baseline levels in the five patients in which a significant decrease in LES pressure had occurred. Metoclopramide did not have any effect on the LES pressure of the other two patients. Thus, we conclude that in patients with chronic respiratory failure, as in normals, there is a subset of individuals in whom negative pressure mechanical ventilatory assistance induces dysfunction of the LES, and that this dysfunction is reversible with metoclopramide. PMID- 1734697 TI - Gastrin release from antral G cells stimulated with secretin. AB - Recently, gastrinoma cells were demonstrated to release gastrin when directly stimulated by secretin both in vivo and in vitro. In this study, the reaction of antral G cells was investigated. Secretin was injected into the right gastroepiploic artery in canines, and into the common hepatic artery during a selective arteriography in patients without gastrinomas. G cells obtained from the antrum of rats were attached to 0.45-microns filters and irrigated with medium containing secretin. The serum gastrin concentration increased rapidly in significant amounts and very quickly after an intraarterial injection of secretin, both in humans and in dogs. The rate of gastrin release from the rat antral G cells in vitro increased significantly when the medium contained secretin. In conclusion, secretin stimulated gastrin release from antral G cells both in vivo and in vitro. PMID- 1734698 TI - Changing epidemiology of gastrointestinal angiodysplasia with increasing recognition of clinically milder cases: angiodysplasia tend to produce mild chronic gastrointestinal bleeding in a study of 47 consecutive patients admitted from 1980-1989. AB - It is important to recognize patients with gastrointestinal bleeding who are at high risk of having angiodysplasia, because these patients should be evaluated by endoscopy rather than barium studies. Sixty-two clinical and epidemiologic parameters were compared between 47 consecutive patients bleeding from angiodysplasia and 47 consecutive controls bleeding from other lesions admitted to two university teaching hospitals from 1980 through 1989. This study demonstrated statistically significant differences between these two groups. The patients with angiodysplasia generally presented with symptoms and clinical findings compatible with hemodynamically well-compensated, chronic bleeding: they were more likely than other gastrointestinal bleeders to experience weakness or fatigue, less likely to experience dizziness or syncope, and less likely to be orthostatic or hypotensive. They had more prior admissions for gastrointestinal bleeding, particularly for gastrointestinal bleeding of undetermined etiology. They were more likely than other gastrointestinal bleeders to be smokers. Patients with angiodysplasia had a milder hospital course: they had fewer transfusions of packed erythrocytes, shorter hospitalizations, and a lower mortality. The in-hospital mortality of patients bleeding from angiodysplasia was 2.1%. Despite the futility of diagnosing angiodysplasia by barium studies, patients ultimately diagnosed as having angiodysplasia were more often initially evaluated by barium studies than the other gastrointestinal bleeders. The currently identified risk factors for bleeding from angiodysplasia should help to select which gastrointestinal bleeders should be evaluated initially by endoscopy. PMID- 1734699 TI - Vincristine-induced paralytic ileus: role of fiberoptic colonoscopy and prostaglandin F2 alpha. AB - Two cases of vincristine-induced paralytic ileus are described, with therapeutic correlation. Both patients had a roentgenographic picture of paralytic ileus showing fecal mass in the ascending colon and dilated bowel loops. One patient was successfully treated with glycerin and saline enema through a fiberoptic colonoscope placed in the ascending colon. The second patient was successfully treated with intravenous prostaglandin F2 alpha (PGF2 alpha). Enema through a fiberoptic colonoscope or the intravenous administration of PGF2 alpha may, therefore, prove useful in the treatment of vincristine-induced gastrointestinal toxicity. PMID- 1734700 TI - Periampullary cysts: endoscopic management. AB - Periampullary cysts are a rare but remediable cause of recurrent pancreatitis. Hitherto, the management of such cysts was mainly surgical. We report on two cases of periampullary cysts. The first patient, who had a cyst of the minor papilla (Santorini cyst), presented with upper gastrointestinal hemorrhage and a history of recurrent pancreatitis. The second patient presented with cholangitis. Both were successfully and safely treated by endoscopic methods alone. Details of the cases and the endoscopic techniques used are fully described. PMID- 1734701 TI - Spontaneous regression of hepatic pseudotumor. AB - Inflammatory pseudotumor of the liver is a rare benign lesion that usually has been discovered at laparotomy and treated by hepatic resection. We report a case of hepatic pseudotumor that was treated without surgery and that subsequently spontaneously resolved. Hepatic pseudotumor occur in all age groups, but most commonly in middle-aged adults, with a 3.5:1 male predominance. Presenting symptoms are 1 or 2 months of fever (66%), abdominal pain (51%), and weight loss (21%). Most often, the lesions are solitary encapsulated tumors composed of whorled laminated fibrous stroma and chronic inflammatory infiltrate. Our report provides documentation of spontaneous resolution of a hepatic pseudotumor. PMID- 1734702 TI - Bile-duct hamartomas presenting as multiple focal lesions on hepatic ultrasonography. AB - Multiple bile-duct hamartomas are usually diagnosed at autopsy as an incidental finding. We report a case of a 50-yr-old male in whom multiple bile-duct hamartomas were suspected in an abdominal ultrasonography and confirmed by an echo-guided needle liver biopsy. The ultrasonography disclosed multiple scattered hyperechoic lesions with a diameter of up to 1 cm, associated with some anechoic lesions of a larger size and a cystic appearance. Computed tomography demonstrated multiple hypodense lesions that were not modified by the administration of contrast. Bile-duct hamartomas should be included in the differential diagnosis of multiple focal hepatic lesions at ultrasonography or computed tomography. PMID- 1734703 TI - Gastrointestinal hemorrhage due to gastrointestinal Mycobacterium avium intracellulare or esophageal candidiasis in patients with the acquired immunodeficiency syndrome. AB - A 33-yr-old black intravenous drug abuser with the acquired immunodeficiency syndrome (AIDS) had a massive fatal upper gastrointestinal hemorrhage due to profound and diffuse esophageal ulceration from Candida, as demonstrated by postmortem examination. A 2-yr-old white male with congenitally acquired AIDS had a massive fatal esophageal bleed as a result of esophagitis from Candida albicans, as proven by pathologic examination and culture of endoscopic biopsies. A 27-yr-old black human immunodeficiency virus-seropositive female died from massive lower gastrointestinal bleeding due to extensive small and large intestinal ulceration caused by Mycobacterium avium intracellulare, as proven by microscopic examination and mycobacterial culture of intestinal tissue. These reports extend the clinical spectrum of these infections in AIDS patients by demonstrating that these infections can produce gastrointestinal bleeding. PMID- 1734704 TI - Mesenteritis ossificans. AB - A unique finding of an extraskeletal pseudomalignant osseous lesion of the mesentery and omentum was detected in a 63-yr-old insulin-dependent diabetic man, following aortic bifemoral bypass and two subsequent laparotomies at 2-wk intervals for intractable intestinal obstruction. An analogy is made to myositis ossificans and fasciitis ossificans. The histogenesis of new bone formation from connective tissue following chemical or physical stimuli supports a metaplastic mechanism. Our review of the literature reveals no prior report of a similar case. PMID- 1734705 TI - Hyperplastic polyp of the common bile duct. AB - We describe a hyperplastic polyp of the common bile duct, found in a 45-yr-old Japanese woman. Endoscopic retrograde sphincterotomy and intraductal biopsy yielded a histological diagnosis of adenocarcinoma, preoperatively. However, final diagnosis after pancreatoduodenectomy proved to be hyperplasia. The wrong diagnosis seemed attributable to tortuosity of the specimens caused by the biopsy procedure and/or a lack of experience of pathologists due to the rarity of this condition. One should be aware of this entity in diagnosing polypoid lesions in the biliary tract. PMID- 1734706 TI - Diplopia and diarrhea: ileal carcinoid metastatic to the central nervous system. AB - The case of a patient with metastatic ileal carcinoid is reported. The peculiarities of this case were as follows: 1) The patient presented with symptoms attributable to a mass lesion in the brain which was proven to be a carcinoid tumor by biopsy. 2) The patient had symptoms attributable to carcinoid syndrome without radiologic evidence of hepatic metastasis. 3) No bony or pulmonary metastasis was evident, which suggests that the metastatic spread from the ileum occurred through the spinous venous plexus of Batson. The patient's symptoms were managed with cyproheptadine with good effect. A review of the carcinoid syndrome and the determinants of its metastatic spread is presented. PMID- 1734707 TI - Gastric perforation after endoscopic treatment of a Dieulafoy's lesion. AB - Dieulafoy's vascular malformation is an underdiagnosed cause of massive, often recurrent upper gastrointestinal hemorrhage. Attempted endoscopic treatment of Dieulafoy's lesion has been recommended prior to surgery in many instances, but may occasionally be employed as primary therapy in patients that are not considered good "operative risks." Although generally considered safe and effective therapy for nonvariceal hemorrhage, combination therapy by injection and thermocoagulation techniques may result in perforation. We present a patient with a Dieulafoy's lesion of the stomach that illustrates both the efficacy and risks of combination endoscopic therapy for nonvariceal gastrointestinal hemorrhage. PMID- 1734708 TI - Closure of a controlled biliary fistula complicating partial cholecystectomy with endoscopic biliary stenting. AB - An elderly woman presented 2 months after partial cholecystectomy performed for gangrenous cholecystitis with choledocholithiasis and a controlled biliary fistula. Despite ductal clearance of stones via endoscopic retrograde sphincterotomy and stone extraction, bilious drainage via the fistulous tract persisted. Endoscopic insertion of a 10F Amsterdam endoprosthesis resulted in complete closure of the fistula within 6 wk. This case represents the first example of closure of a biliary fistula after partial cholecystectomy. PMID- 1734709 TI - Simvastatin-induced protein-losing enteropathy. PMID- 1734710 TI - Biliary ectasia in a patient with Marfan's syndrome. PMID- 1734711 TI - Debates, divisions, and decisions: recombinant DNA advisory committee (RAC) authorization of the first human gene transfer experiments. AB - Possibly the most far-reaching, controversial research currently being conducted in the international biological science community involves human gene therapy experimentation. In this paper, I report the dynamics of the political process which ultimately found the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health approving for the first time protocols of this genre. A full appreciation of the policy-making dialogue shows that significant participants perceived the process from very different vantage points regarding the way in which the American political system works and the way in which it ought to work. I argue that, if we are to understand how the RAC should proceed in orchestrating a human gene therapy policy agenda, then we must flesh out and critically analyze these competing vantage points. To that end, I postulate seven possible "action models" for characterizing how protocol assessments of the type at issue might be developed given the nature of our politics, reaching the conclusion that one of these models holds out the most promise for synthesizing efficaciously the key factors involved. In conclusion, I discuss how the RAC might profitably employ this preferred strategy in these and other cases. PMID- 1734712 TI - Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis. AB - Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and stereotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Maternal and paternal X chromosomes from the affected sisters were separated in somatic cell hybrids and were examined for concordance/discordance of maternal alleles at the tested loci. Thirty-six markers were informative in at least one of the two families, and 25 markers were informative in both families. Twenty loci were excluded as candidates for the Rett syndrome gene, on the basis of discordance for maternal alleles in the half-sisters. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than -2, we were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed. This in turn will result in a defined region of the X chromosome that should be searched for candidate sequences for the Rett syndrome gene in both familial and sporadic cases. PMID- 1734713 TI - The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes. AB - Amelogenins, a family of extracellular matrix proteins of the dental enamel, are transiently but abundantly expressed by ameloblasts during tooth development. Amelogenins seem to regulate the formation of crystallites during the secretory stage of enamel development, while they are specifically degraded during tooth bud maturation. In this paper we report the characterization of the AMGX and AMGY genes on the short arms of the human X and Y chromosomes which encode the amelogenins. Our studies on the expression of the amelogenin genes in male developing tooth buds showed that both the AMGX and AMGY genes are transcriptionally active and encode potentially functional proteins. We have isolated genomic and cDNA clones from both the AMGX and AMGY loci and have studied the sequence organization of these two genes. Reverse transcriptase (RT)PCR amplification of the 5' portion of the amelogenin transcripts revealed several alternatively spliced products. The splicing pattern observed in the Y derived mRNA varies from that of the X-derived mRNA. The promoter regions from both genes and the predicted amelogenin protein sequences are presented. This information will be useful for studying the molecular basis of X-linked amelogenesis imperfecta, for understanding the evolution and regulation of gene expression on the mammalian sex chromosomes, and for investigating the role of amelogenin genes during tooth development. PMID- 1734714 TI - Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21. AB - McLeod syndrome, characterized by acanthocytosis and the absence of a red-blood cell Kell antigen (Kx), is a multisystem disorder involving a late-onset myopathy, splenomegaly, and neurological defects. The locus for this syndrome has been mapped, by deletion analysis, to a region between the loci for Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In this study, we describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG islands were found clustered in a 700-kb region. Using the new marker, we have limited the McLeod syndrome critical region to 150-380-kb. Within this interval, two CpG-rich islands which may represent candidate sites for the McLeod gene were identified. PMID- 1734715 TI - A multiple-tubes approach for accurate genotyping of very small DNA samples by using PCR: statistical considerations. AB - A multiple-tubes procedure is described for using PCR to determine the genotype of a very small DNA sample. The procedure involves dividing the sample among several tubes, then amplifying and typing the contents of each tube separately. The results are analyzed by a statistical procedure which determines whether a genotype can be conclusively assigned to the DNA sample. Simulation studies show that this procedure usually gives correct results even when the number of double stranded fragments in the sample is as small as 30. The procedure remains effective even in the presence of small amounts of laboratory contamination. We find that the multiple-tubes procedure is superior to the standard one-tube procedure, either when the sample is small or when laboratory contamination is a potential problem; and we recommend its use in these situations. Because the procedure is statistical, it allows the degree of certainty in the result to be quantified and may be useful in other PCR applications as well. PMID- 1734716 TI - Lack of transmission of deleted mtDNA from a woman with Kearns-Sayre syndrome to her child. AB - We have investigated the daughter of a woman with Kearns-Sayre syndrome. The woman had a high percentage of deleted mtDNA in muscle, but no deleted mtDNA was detected in fibroblasts, bone marrow, and peripheral blood cells by Southern blot analysis. With PCR, analytical sensitivity was significantly increased, and deleted mtDNA was detected in all examined tissues from this patient. The patient had healthy parents and nine healthy siblings. No deleted mtDNA was detected in blood from the mother of the patient. The patient had an uneventful pregnancy and delivered at term. Deleted mtDNA could not be detected in placenta by Southern blot analysis. With PCR, deleted mtDNA was detected in the majority of placental specimens. This finding may, however, be due to contamination with maternal DNA. The patient's daughter was healthy at age 5 mo, and morphologic examination of muscle was normal. No transmission of deleted mtDNA to the daughter could be detected by Southern blot and PCR analysis of peripheral blood cells, bone marrow, fibroblasts, and muscle. The presence of deleted mtDNA was excluded at a fractional level of less than 1:100,000 in all examined tissues from the daughter. PMID- 1734717 TI - Amplification and characterization of the retinoblastoma gene VNTR by PCR. AB - VNTR regions are informative genetic markers for linkage mapping and individual identification. Using PCR, we have developed a procedure for the enzymatic amplification of the VNTR located in the 16th intron of the human retinoblastoma (RB1) gene. We have also prepared a nonisotopically labeled oligonucleotide probe which facilitates detection of the amplification products. In examining 250 individuals from four different populations, we have detected 11 alleles ranging from 650 to 1,800 bp in size. The core repeat is approximately 50 bp in length. On the basis of the observed allele frequencies for Caucasian, African-American, and Hispanic populations from the United States and for the Mexican Hispanic population, the heterozygosities have been calculated to be 62%, 75%, 61%, and 50%, respectively. The observed genotype frequencies do not deviate from the values expected under Hardy-Weinberg equilibrium. The effect of varying primer sequences, annealing temperature, and cycle number on the amplification are also discussed. Amplification of this marker may also prove useful for detecting the heterozygosity loss that is associated with tumor formation in retinoblastoma. PMID- 1734718 TI - The origin of glucose-6-phosphate-dehydrogenase (G6PD) polymorphisms in African Americans. AB - DNA samples from 54 male Afro-Americans were examined for glucose-6-phosphate dehydrogenase (G6PD) genotypes G6PD A(+)376G, G6PD A(-)202A/376G, and G6PD B and for polymorphisms in intron 5 (PvuII), at nucleotide 1311, and at nucleotide 1116 (PstI). In the G6PD B subjects, the nucleotide 1311 mutation and the PstI site appeared to be in linkage equilibrium. No PvuII+ G6PD men were encountered. The G6PD A(+) mutation was in disequilibrium with respect to both the nucleotide 1311 mutation and the PstI site. The G6PD A- nucleotide 202 mutation was in disequilibrium with all three polymorphic sites. No conclusion could be drawn with respect to the PvuII site, except that it preceded the nucleotide 202 (A-) mutation. We conclude from these and our previous studies that G6PD B is the most ancient genotype. The nucleotide 1311 mutation, with its worldwide distribution, probably occurred next. The PstI mutation, limited to Africans, probably arose next and is more ancient than the A(+) mutation, which occurred in a gene without either the PstI or the 1311 mutation. G6PD A-202A/376G is the most recent of these mutations and is still in linkage disequilibrium with all of the sites. Presumably it occurred in an individual with both the A(+) and PvuII mutations. PMID- 1734719 TI - Fine-scale mapping of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1). AB - We have constructed a high-resolution genetic linkage map in the vicinity of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). The mutation causing this disease, inherited as an autosomal dominant, predisposes carriers to development of neoplastic tumors in the parathyroid, the endocrine pancreas, and the anterior lobe of the pituitary. The 12 markers on the genetic linkage map reported here span nearly 20 cM, and linkage analysis of MEN1 pedigrees has placed the MEN1 locus within the 8-cM region between D11S480 and D11S546. The markers on this map will be useful for prenatal or presymptomatic diagnosis of individuals in families that segregate a mutant allele of the MEN1 gene. PMID- 1734720 TI - Interethnic genetic differentiation in Africa: HLA class I antigens in The Gambia. AB - A total of 752 individuals from The Gambia, west Africa who are representative of the major ethnic groups in the capital, Banjul, were serologically typed for HLA A, -B, and -C antigens. Although all were typically "African" in their antigenic profiles, some marked frequency differences were found between the ethnic groups. Genetic distance comparisons with several other African populations showed that, although these west African populations clustered closely together, the positions of the various ethnic groups in The Gambia were consistent with historical and linguistic evidence of their affinities with one another and with other African populations. Despite the potential confounding effects both of selection by infectious diseases and of genetic drift caused by local differences in population structure, HLA frequencies appear to be of value in measuring inter- and intraregional population affinities in sub-Saharan Africa. PMID- 1734721 TI - Molecular characterization of beta-thalassemia in the Sardinian population. AB - This study reports the molecular characterization of beta-thalassemia in the Sardinian population. Three thousand beta-thalassemia chromosomes from prospective parents presenting at the genetic service were initially analyzed by dot blot analysis with oligonucleotide probes complementary to the most common beta-thalassemia mutations in the Mediterranean at-risk populations. the mutations which remained uncharacterized by this approach were defined by denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis on amplified DNA. We reconfirmed that the predominant mutation in the Sardinian population is the codon 39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes. The other two relatively common mutations are frameshifts at codon 6 (2.1%) and at codon 76 (0.7%), relatively uncommon in other Mediterranean-origin populations. In this study we have detected a novel beta-thalassemia mutation, i.e., a frameshift at codon 1, in three beta thalassemia chromosomes. The DGGE procedure followed by direct sequencing on amplified DNA is a powerful approach for the characterization of unknown mutations in this genetic system. The results herein presented allowed an expansion of the applicability of prenatal diagnosis by DNA analysis, to all couples at risk for beta-thalassemia in our population. PMID- 1734722 TI - A nonsense mutation in the LDL receptor gene leads to familial hypercholesterolemia in the Druze sect. AB - Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the LDL receptor gene. Here we characterize an LDL receptor mutation that is associated with a distinct haplotype and causes FH in the Druze, a small Middle Eastern Islamic sect with a high degree of inbreeding. The mutation was found in FH families from two distinct Druze villages from the Golan Heights (northern Israel). It was not found neither in another Druze FH family residing in a different geographical area nor in eight Arab and four Jewish FH heterozygote index cases whose hypercholesterolemia cosegregates with an identical LDL receptor gene haplotype. The mutation, a single-base substitution, results in a termination codon in exon 4 of the LDL receptor gene that encodes for the fourth repeat of the binding domain of the mature receptor. It can be diagnosed by allele-specific oligonucleotide hybridization of PCR-amplified DNA from FH patients. PMID- 1734723 TI - General population screening for cystic fibrosis is premature. PMID- 1734724 TI - Advantages of a two-step laboratory approach for cystic fibrosis carrier screening. PMID- 1734725 TI - Population genetic issues in DNA fingerprinting. PMID- 1734726 TI - Molecular genetic analysis of a sporadic case of Leber hereditary optic neuropathy. PMID- 1734727 TI - Leber optic neuropathy. PMID- 1734728 TI - Informative microsatellite markers allow carrier detection in a Duchenne muscular dystrophy deletion pedigree in the absence of DNA from an affected boy. PMID- 1734729 TI - Chest pain and breathlessness: relationship to psychiatric illness. AB - Chest pain and breathlessness are common somatic symptoms of emotional disorder in ambulatory care. Chronic chest pain has a prevalence of 12% and is associated with high utilization of health care. Of patients with chest pain and breathlessness who are referred to a cardiac clinic but subsequently shown not to have heart disease, the majority continue to report symptoms. Those patients with the worst outcome, in terms of continuing limitation of activity and use of medical resources, are those with chest pain but normal coronary arteries. A number of studies that fail to support a unitary theory of causation of noncardiac chest pain are described. A multifactorial, interactive model is proposed, with contributions from physical factors, such as palpitations and intercostal muscle pain; psychologic factors, which include enhanced awareness of and selective attention to bodily sensation; and environmental factors, such as previous exposure to cardiorespiratory disease in first-degree relatives or significant others. Although there have been few controlled intervention studies in patients with unexplained cardiorespiratory symptoms, there is evidence for the efficacy of both drug treatments and psychologic treatment. The results of intervention studies in patients with chest pain and normal coronary arteries are eagerly awaited. Atypical chest pain and breathlessness are common causes of office consultations and/or functional disability. The diagnoses should be established on the basis of positive evidence of psychiatric illness rather than by exclusion. The etiology is multifactorial, and management is aimed at treating the underlying psychosocial problems and/or psychiatric illness. Cognitive behavioral treatments are probably as effective as drug treatments in the short term, and the care of these patients would be improved by a more detailed explanation of noncardiac causes and a greater opportunity for patients to discuss their fears. PMID- 1734730 TI - Medically unexplained syncope: relationship to psychiatric illness. AB - The purpose of this article is to review the literature and present new data concerning the relationship between psychiatric disorders and unexplained syncope. Several case series are presented of patients with syncope in whom psychiatric structured interviews were undertaken, tilt-table (physiologic) testing was performed, and health-related quality of life was measured. Patients seen in a syncope specialty clinic underwent structured psychiatric interviews in addition to in-depth medical evaluations. Tilt-table testing was performed on a separate series of patients to determine susceptibility to syncope during the orthostatic challenge of head-up tilt; in some cases, tilt studies included simultaneous electroencephalographic (EEG) monitoring and cerebral blood flow measurements. Formal functional status assessment was carried out using the Sickness Impact Profile, the Symptom Check List 90, and the Medical Outcomes Study Short-Form 36. Psychiatric disorders (in particular, panic disorders and major depression) were a common cause of syncope (24-31% of syncope patients). Tilt table studies showed several physiologic profiles in syncope: (a) a typical vasovagal (hypotension-bradycardia) response, (b) a "psychosomatic" response (fainting with normal vital signs), and (c) a gradual decline in blood pressure (dysautonomic response). EEG and cerebral blood flow measurements in three patients with the psychosomatic response to tilt were normal during fainting. Functional status measurements showed serious impairment in two series of syncope patients. Conclusions were as follows: (a) Psychiatric disorders are common in syncope. (b) Tilt-table methodology may elucidate underlying mechanisms of syncope in these subjects. (c) Syncope can seriously disrupt a patient's life and result in important psychosocial sequelae. (d) There is an intimate relationship between unexplained syncope and psychiatric illness, mandating a combined medical and psychiatric approach to such patients. PMID- 1734731 TI - Symptoms in medical patients: an untended field. AB - Somatic symptoms are one of the leading reasons for medical outpatient clinic visits, with the most common symptoms having a prevalence of 10% or more. However, the usual diagnostic workups are often unproductive, with less than 1 in 5 symptoms having an organic explanation after the initial physical examination and laboratory testing. Therapy appears more effective for some symptoms than for others. Of patients with unspecified pain or gastrointestinal complaints, greater than 70% state that some type of treatment has been helpful, whereas less than 50% of individuals with fatigue, dizziness, numbness, insomnia, sexual dysfunction, anxiety, or depression report any relief. Future educational efforts and research need to focus on that majority of symptoms that are either psychiatric or unexplained, in order to improve our current evaluation and management strategies. PMID- 1734732 TI - Palpitations, cardiac awareness, and panic disorder. AB - This article reviews and appraises a variety of studies on panic disorder, visceral sensitivity, and cardiac disease. The literature reviewed includes descriptive surveys, small-scale experimental manipulations, and clinical interventions. Instruments have included structured diagnostic interviews, clinical observation, self-report inventories, direct measures of perceptual sensitivity, and cognitive tests. The subjects in these studies have ranged from community residents to carefully defined samples of designated patients with psychiatric or cardiac disease. We then outline a prospective investigation to examine the prominence of palpitations in panic anxiety and speculate on the importance of sensitivity to cardiac sensation in several other clinical conditions characterized by marked discrepancies between cardiac activity and cardiac symptoms. PMID- 1734733 TI - Physician consultation for headache pain and history of panic: results from a population-based study. AB - In a population-based telephone interview survey of 10,169 respondents aged 12-29 years in Washington County, Maryland, data were collected on history of panic attacks, on the most recent headache and associated symptoms in the 2 weeks before the interview, and on physician consultation for headache-related problems. Of those who had a headache in the previous 12 months, 14.2% of females and 5.8% of males consulted a physician for headache. The proportion who recently consulted a physician increased with age among females but not among males. An unexpectedly high proportion of those who recently sought physician care for their headache problem had a history of panic. In particular, among those who sought care, 15% of females and 12.8% of males ages 24-29 had a history of panic disorder. Overall, females with panic disorder who had recently seen a physician for headache exhibited the most frequent, severe, and complex headaches. In particular, headaches were of considerably longer duration, more severe, and greater than 50% of these females had five or more headaches in a 4-week period. A very high proportion experienced disability (up to 46.7%) from their headache. Males with a history of panic who did or did not seek physician care differed only in that a considerably higher proportion of the former group (up to 45%) had frequent headaches. Overall, 11.8% of the total population had a migraine headache in the 2 weeks before the interview. In contrast, 21.8% of those who sought physician care and 36% of those with panic disorder who sought physician care had a migraine headache. PMID- 1734734 TI - Panic disorder: relationship to high medical utilization. AB - The purpose of this review is to describe the relationship between panic disorder, somatization, functional disability, and high medical utilization. Data from community, primary-care, and specialty studies were reviewed to determine the prevalence of anxiety and panic disorder in these populations. Data from the Epidemiologic Catchment Area Study were reviewed to emphasize the effect of panic disorder on health-care utilization and health perception in a community population. Data on the prevalence of panic disorder in primary care and mode of presentation of primary-care patients with panic disorder were also reviewed. Finally, the epidemiologic psychiatric findings from our recent study of distressed high utilizers of primary care were presented. Panic disorder was found to occur in 1-3% of people in the study community and 1.4-8% of primary care patients. Of people with or without psychiatric disorder, people with panic disorder in the community had the highest risk of having multiple medically unexplained symptoms and of being high utilizers of medical ambulatory services. People with panic disorder in the community compared to both community psychiatric and nonpsychiatric controls tend to perceive themselves as having poor physical health and to be high users of emergency and hospital inpatient services, as well as ambulatory services. Most patients with panic disorder present to their primary-care physician with somatic complaints, especially cardiac (tachycardia, chest pain), gastrointestinal (epigastric pain or irritable bowel syndrome), or neurologic complaints (headaches, dizziness, or presyncope). Patients who were distressed high utilizers of primary care had an extremely high prevalence of current panic disorder (12%) and lifetime panic disorder (30%), which supported the association between panic disorder and high medical utilization found in the Epidemiologic Catchment Area (ECA) Study. PMID- 1734735 TI - Is sleep deprivation useful in the treatment of depression? AB - OBJECTIVE: The authors critically reviewed the literature on clinical applications of sleep deprivation in the treatment of depression. DATA COLLECTION: They included all studies using sleep deprivation for clinical purposes, with the exception of treatment studies that did not provide follow-up beyond a night of recovery sleep. They focused on six uses of sleep deprivation: 1) to potentiate response to antidepressant medication (13 studies), 2) to hasten the onset of action of antidepressant medication or lithium (five studies), 3) to prevent recurrent mood cycles (four studies), 4) as an alternative to antidepressant medication (five studies), 5) as a diagnostic probe (two studies), and 6) to predict response to antidepressant medication (nine studies). FINDINGS: Although the literature appears to demonstrate the efficacy of sleep deprivation as a potentiation strategy, these treatment studies have substantial methodological shortcomings. Well-designed pilot studies indicate that sleep deprivation may hasten the onset of action of thymoleptic medications. Sleep deprivation may prevent premenstrual mood swings, and response to sleep deprivation may differentiate depressive pseudodementia from primary degenerative dementia with depression. Studies attempting to use sleep deprivation to predict response to antidepressant medication have yielded inconsistent results. CONCLUSIONS: Given the noninvasive nature of sleep deprivation, it would be useful to determine if even a small subset of refractory patients respond to it. The authors suggest future research directions to determine the usefulness of this potential treatment. PMID- 1734736 TI - Community mental health and mental retardation services in the United States: a comparative study of resource allocation. AB - OBJECTIVE: Preliminary studies suggest that during the 1980s, spending for community mental retardation services in the United States may have grown much more rapidly than spending for community mental health. The primary objective of this study was to test empirically the validity of this thesis on a national basis. An additional objective was to determine why such a distinction in community spending patterns might have evolved nationally. METHOD: The study used states as the units of analysis and employed a five-factor hierarchical regression to predict variance in mental health and mental retardation spending. Factors were state size, state wealth, degree of federal assistance, state civil rights activity, and strength of consumer advocacy groups. Strong roles for the civil rights and consumer advocacy factors were hypothesized. A collateral opinion survey in the 10 states exhibiting the greatest within-state difference in community mental health and mental retardation spending was also completed. RESULTS: Community mental retardation spending grew nearly four times more rapidly than community mental health spending in the 1980s. The consumer advocacy and civil rights factors were strongly associated with spending for community mental retardation services in the states, but these factors did not predict spending for community mental health services. CONCLUSIONS: Study recommendations included strengthening mental health family and consumer advocacy groups in the states and promoting systematic exchange between the mental health and mental retardation fields through joint state planning initiatives, studies, and conferences. The need for Medicaid reform is a unifying theme in both the mental health and mental retardation fields. PMID- 1734737 TI - Cognitive deficits of patients with Alzheimer's disease with and without delusions. AB - OBJECTIVE: The goal of this investigation was to study the prevalence of delusions in Alzheimer's disease and to compare the performance of the delusional and nondelusional groups on a neuropsychological test battery. METHOD: The authors studied 107 patients with Alzheimer's disease and 51 age- and education comparable normal subjects using a standardized psychiatric interview and a neuropsychological test battery. RESULTS: Thirty-seven patients with Alzheimer's disease had delusions with or without hallucinations. Patients with delusions were significantly more impaired than those without delusions (and the normal comparison group) on the Mini-Mental State examination; Blessed Information Memory-Concentration Test; Dementia Rating Scale, especially its conceptualization and memory subtests; and a test of verbal fluency. The delusional group also tended to be somewhat more impaired than the nondelusional group on the modified Wisconsin Card Sorting Test and the similarities subtest of the Wechsler Adult Intelligence Scale-revised. CONCLUSIONS: Approximately one third of patients with Alzheimer's disease had developed psychotic symptoms sometime after the onset of dementia. The presence of psychotic symptoms in Alzheimer's disease was associated with greater cognitive impairment, especially frontal/temporal dysfunction, and possibly with a more rapidly progressive dementia. PMID- 1734738 TI - An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease. AB - OBJECTIVE: Although the Global Deterioration Scale has been widely used since its publication in 1982, its stages are based on implicit assumptions about the linearity, temporality, and interdependence of cognitive, functional, and behavioral impairment in Alzheimer's disease. The authors evaluated the validity of these assumptions and tested the hypothesis that psychopathology and functional impairment would occur in earlier stages than the Global Deterioration Scale predicts. METHOD: The analyses were based on data on 324 patients with Alzheimer's disease who were selected from a registry of such patients. Data analyses included 1) descriptive statistics on the frequency of psychiatric symptoms and difficulties with activities of daily living and 2) logistic regression, with symptoms and functional impairment as independent variables, to test for significant changes in patients' status between stages of the Global Deterioration Scale. RESULTS: More than 50% of the patients at stage 2 displayed psychopathology, and 32% had two or more symptoms. The significant increase in psychiatric symptoms occurred between stages 3 and 4, not between stages 5 and 6 as predicted by the Global Deterioration Scale. Impairment in functional status was observed at all stages, and significant increases occurred between stages 3 and 4 as well as between stages 5 and 6. CONCLUSIONS: Psychiatric symptoms and functional impairment occur earlier than predicted by the Global Deterioration Scale, and the rate of change is also different from that specified in the scale. Separate scales to describe cognitive, clinical, and functional status may be the best way to describe the illness until better multidimensional instruments are developed. PMID- 1734739 TI - Treatment of imipramine-resistant recurrent depression, IV: A double-blind crossover study of tranylcypromine for anergic bipolar depression. AB - OBJECTIVE: Few trials of monoamine oxidase inhibitors (MAOIs) in tricyclic resistant depression have had double-blind conditions. In the authors' previous double-blind comparison of tranylcypromine and imipramine in anergic bipolar depression, tranylcypromine was significantly more effective. This investigation was a crossover study of nonresponders in the initial study. METHOD: The subjects were 16 outpatients with anergic bipolar depression. Fourteen had not responded to 4 weeks of treatment with at least 30 mg/day of tranylcypromine or 150 mg/day of imipramine, and two patients were crossed over because of intolerable side effects from the initial drug. The crossover medication was prescribed as in the initial double-blind study. RESULTS: Twelve patients were crossed over from imipramine to tranylcypromine; nine of them responded to tranylcypromine. Highly significant improvements were documented on the Hamilton, Beck, and Pittsburgh Reversed Vegetative Symptom Scales. Four patients were switched from tranylcypromine to imipramine, but only one responded. CONCLUSIONS: The high rates of response to tranylcypromine in both the initial and crossover double blind studies document the efficacy of MAOI treatment for anergic bipolar depression. Moreover, the results further illustrate the utility of MAOIs in tricyclic-resistant depressions. PMID- 1734740 TI - Controlled investigation of the amobarbital interview for catatonic mutism. AB - OBJECTIVE: Clinical reports over the last 60 years suggest that the amobarbital interview is effective in relieving catatonic symptoms. This has never been substantiated with methodologically sound trials. The authors postulated that a randomized blind comparison of intravenous amobarbital and saline would demonstrate the superiority of amobarbital in relieving catatonic mutism. METHOD: The subjects were 20 inpatients with catatonic mutism. They were randomly assigned to either saline (N = 10) or a 5% amobarbital solution (N = 10), and the infusions were administered intravenously at a rate of 1 cc/min or less over 10 minutes by a blinded physician. A second blinded physician administered a semistructured interview during the infusion to control for the effect of suggestion. A third blinded physician rated patient responsiveness, reactivity, and arousal. Any patient who was unresponsive to the initial infusion was crossed over to the other infusion. Interviews were videotaped for determination of interrater reliability. RESULTS: In the initial infusions, six of 10 patients responded to amobarbital and zero of 10 responded to saline. Four of the saline nonresponders responded when given amobarbital. Response was evident by the 4th minute of the amobarbital infusion. Interrater reliability was high. The responders and nonresponders differed significantly in the variance of the weight adjusted amobarbital dose, and the responders tended to be older and female. CONCLUSIONS: Intravenous amobarbital is superior to saline in relieving catatonic mutism, although only 50% of these patients responded. The nonresponders were distinguished from the responders by a greater variance in the weight-adjusted dose of amobarbital. PMID- 1734741 TI - The role of violence in decisions about hospitalization from the psychiatric emergency room. AB - OBJECTIVE: The authors evaluated the relationship between violent behavior and decision making about hospitalization from the psychiatric emergency room. METHOD: The medical charts of 321 patients evaluated in an urban psychiatric emergency room during a 4-week period were reviewed retrospectively. Violent behavior was defined as physical attacks on persons or fear-inducing behavior before or during the evaluation in the emergency room; and its value in predicting hospitalization decisions was assessed with logistic regression analyses that also included 12 demographic, clinical, and contextual variables. RESULTS: A model predicting hospitalization decisions was developed and cross validated. Although violent patients were more likely to be hospitalized than nonviolent patients, clinical variables such as diagnosis and overall severity of psychiatric impairment were more important than violent behavior in predicting hospitalization decisions. CONCLUSIONS: Despite legal pressures to focus on overt behaviors such as violence as a basis for liability prevention and civil commitment, clinicians in this study did not allocate inpatient resources to preventively detain persons unlikely to benefit from treatment. Rather, they hospitalized the most severely disturbed patients, with diagnoses such as schizophrenic and manic disorders for which a widely accepted therapeutic armamentarium exists. The results are consistent with clinical recommendations that in the evaluation of the violent patient, attention needs to be given to the underlying disorder, since violent behavior itself can result from diverse causes only some of which require inpatient psychiatric treatment. PMID- 1734742 TI - Diagnosis of DSM-III-R personality disorders by two structured interviews: patterns of comorbidity. AB - OBJECTIVE: The purpose of this study was to examine patterns of co-occurrence of axis II disorders in a group of consecutive patients evaluated with two contrasting structured interviews. METHOD: One hundred of 106 consecutive applicants for long-term, inpatient treatment of severe personality psychopathology were assessed, face-to-face, by psychiatrists using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and the Personality Disorder Examination (PDE). The percent of co-occurrence of pairs of disorders diagnosed by each structured interview separately was calculated, and significance levels were determined by using chi-square tests of independence. Finally, odds ratios were computed for the odds of each pair of disorders occurring together compared with the odds for the occurrence of each disorder alone. RESULTS: The two interview methods revealed different comorbidity patterns. Significant covariation was found for 29 pairs of disorders diagnosed with the PDE, compared with 12 pairs diagnosed with the SCID-II. Six pairs of disorders covaried significantly and were associated with odds ratios greater than 4: histrionic with borderline, histrionic with narcissistic, narcissistic with antisocial, narcissistic with passive-aggressive, avoidant with schizotypal, and avoidant with dependent. CONCLUSIONS: Substantial overlap occurred among personality disorders. In this group of patients, consistent patterns of comorbidity involving narcissistic, avoidant, and histrionic personality disorders suggest that categorical distinctions between them and certain other DSM-III-R personality disorders may be illusory. The question of which of two overlapping disorders is more valid, however, is left unanswered. For clinical purposes, a two-level diagnostic convention is proposed. PMID- 1734743 TI - Self-mutilation in personality disorders: psychological and biological correlates. AB - OBJECTIVE: The goal of this study was to determine whether self-mutilators with personality disorders differ from nonmutilators with personality disorders in impulsivity, aggression, and other psychopathology and whether serotonergic dysfunction contributes to self-mutilation. METHOD: Twenty-six self-mutilators with personality disorders were matched to 26 control subjects with personality disorders for gender, age, education, axis I diagnosis of affective disorder, and axis II diagnosis of personality disorder. Numerous indexes of psychopathology as well as CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and platelet imipramine binding sites (Bmax) and affinity (Kd) were determined. RESULTS: Self-mutilators had significantly more severe character pathology, had greater lifetime aggression, and were more antisocial than the control subjects. The self mutilators scored higher on the Hamilton Rating Scale for Depression but not on the Beck Depression Inventory or the Beck Hopelessness Scale. The two groups did not differ on the Buss-Durkee Hostility and Guilt Inventory or on the Sensation Seeking Scale. The degree of self-mutilation was significantly correlated with impulsivity, chronic anger, and somatic anxiety. Both self-mutilation and impulsivity showed significant negative correlations with Bmax, although the two groups did not differ in CSF 5-HIAA levels or in platelet imipramine binding. CONCLUSIONS: The results demonstrate the contribution of severe character pathology, aggression, impulsivity, anxiety, and anger to self-mutilation and provide preliminary support for the hypothesis of underlying serotonergic dysfunction facilitating self-mutilation. PMID- 1734744 TI - Prevalence of mental disorder in 88 morbidly obese bariatric clinic patients. AB - OBJECTIVE: The authors sought to determine the association between mental disorder and morbid obesity, defined as weight at least 100% or 100 lb over ideal body weight. METHOD: Eighty-eight morbidly obese subjects who had come to a tertiary care center surgery clinic requesting vertical banded gastroplasty were systematically interviewed with the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and the Structured Interview for DSM-III Personality Disorders. A comparison group of 76 psychiatrically normal subjects who were matched in age (within 5 years) and gender to the morbidly obese subjects were also interviewed. RESULTS: Most of the morbidly obese subjects were women, were of low socioeconomic status as indicated by method of payment for medical care, weighed more than 300 lb, and had been obese for more than 14 years. The morbidly obese subjects were more likely than the comparison group to have a lifetime history of mood disorders, anxiety disorders, bulimia, and tobacco dependence. The morbidly obese subjects were also more likely to meet diagnostic criteria for one or more personality disorders. CONCLUSIONS: Substantial psychopathology exists in morbidly obese individuals requesting gastroplasty, a finding that has important clinical implications. PMID- 1734745 TI - Patients who use drugs during inpatient substance abuse treatment. AB - OBJECTIVE: Drug use by patients during inpatient substance abuse treatment is frequently a cause of premature hospital discharge. The authors examined the histories of patients who used drugs while in inpatient substance abuse treatment, the methods used to detect drug use, and the temporal relationship of drug use episodes. METHOD: The authors reviewed the charts of patients admitted consecutively to an inpatient substance abuse treatment unit between 1981 and 1988. Of 729 patients, 42 were found to have used drugs while receiving inpatient treatment. The diagnoses and clinical histories of these 42 patients were compared with those of all other patients. Methods of detection and circumstances of drug use were recorded, and drug use episodes were plotted on a time line that was examined for temporal clustering. RESULTS: Significantly more of the patients who used drugs during inpatient substance abuse treatment had primarily used heroin or methadone before treatment. Random urine screens, self-report, and staff observation together detected approximately 85% of the patients who used drugs during treatment. Episodes of drug use did cluster in time, but within clusters the hospital stays of the patients who used drugs did not necessarily overlap. CONCLUSIONS: Temporal clustering of drug use episodes may occur because drug use by one patient heralds drug availability and stimulates craving in other inpatients. Clinicians should be aware that one episode of drug use may be followed by others. Multiple detection methods, including random comprehensive urine screens, should be used to test for drug use on inpatient units. PMID- 1734746 TI - Now is the time to retire the term "organic mental disorders". AB - The organic/nonorganic distinction in contemporary classifications of mental disorders such as DSM-III and DSM-III-R has important prognostic and treatment implications, because it directs the clinician to pay special attention to the possibility of an underlying "physical" disorder as the cause of the mental disturbance. However, the term "organic" raises serious and intractable problems, since the connotative meaning of the term always returns to its historical roots, which imply an outmoded functional/structural, psychological/biological, and mind/body dualism. The authors present a proposal being considered for DSM-IV that would eliminate the term "organic" and reorganize the classification of organic mental disorders. Disorders previously referred to as "organic mental disorders" would be renamed as either "secondary disorders" (if they are due to "physical" disorders) or "substance-induced disorders." The entire classification of mental disorders would be reorganized to distribute the secondary and substance-induced disorders into the major groups with which they share phenomenology. The traditional organic mental disorders--delirium, dementia, and amnestic disorder--would be grouped together under the rubric of "cognitive impairment disorders." While acknowledging problems with the suggested new terminology and reorganization of the classification, the authors argue that the potential benefits of the proposal for clarity and for facilitating differential diagnosis justify putting to rest the familiar but now anachronistic term "organic mental disorders." PMID- 1734747 TI - Magnetic resonance imaging of the posterior fossa in autistic adults. AB - Magnetic resonance imaging measurements were obtained for 12 adults with DSM-III defined autism and a matched group of 12 normal subjects. No significant differences were found for mean midsagittal areas of pons, fourth ventricle, cerebellar vermis, or vermis lobules. No significant brain abnormalities were observed in either group. PMID- 1734748 TI - High-intensity signals in Alzheimer's disease without cerebrovascular risk factors: a magnetic resonance imaging evaluation. AB - The authors examined the relationship between Alzheimer's disease, without cerebrovascular risk factors, and high-intensity signals on magnetic resonance imaging (MRI) with a 1.5-tesla scanner. There were no significant differences in MRI high-intensity signals between subjects with Alzheimer's disease (N = 16) and healthy control subjects (N = 23). PMID- 1734749 TI - Glutamate and other CSF amino acids in Alzheimer's disease. AB - The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease. PMID- 1734750 TI - Modified activity of the human auditory cortex during auditory hallucinations. AB - Previous reports have shown abnormalities in brain metabolism and evoked responses of schizophrenic patients with hallucinations. The authors recorded electric and magnetic auditory responses during transitory auditory hallucinations in two patients. Small but replicable response delays occurred during hallucinations. The results suggest that the effect of hallucinations on auditory cortex activity is similar to the effect of real sounds. PMID- 1734751 TI - Brief anabolic steroid use and sustained behavioral reaction. PMID- 1734752 TI - Development of transient obsessive-compulsive symptoms during treatment with clozapine. PMID- 1734753 TI - Clozapine-induced priapism. PMID- 1734754 TI - Control of depression with fluoxetine and antiseizure medication in a brain injured patient. PMID- 1734755 TI - Automobile driving by psychiatric patients. PMID- 1734756 TI - "Pseudohypermnesia": a conscious effort to avoid telling the truth. PMID- 1734757 TI - Sequelae of denied abortion. PMID- 1734758 TI - Meaning of refractory depression. PMID- 1734759 TI - Meaning of refractory depression. PMID- 1734760 TI - Performance anxiety. PMID- 1734761 TI - Factors in homelessness among psychiatric patients. PMID- 1734762 TI - The mind-body problem. PMID- 1734763 TI - The mind-body problem. PMID- 1734764 TI - When a patient commits suicide. PMID- 1734765 TI - When a patient commits suicide. PMID- 1734766 TI - Further comments on trichotillomania. PMID- 1734767 TI - Further comments on trichotillomania. PMID- 1734768 TI - Lectures in anesthesia training. PMID- 1734769 TI - Is resting membrane potential a possible indicator of viability of muscle bundles used in the in vitro caffeine contracture test? AB - In 22 patients susceptible to and 34 patients not susceptible to malignant hyperthermia, we examined which muscle conditions may influence the degree of sensitivity of skeletal muscle to the in vitro caffeine contracture test: predrug resting membrane potential, predrug twitch tension, and maximum contracture induced by 32 mM caffeine in two caffeine tests performed respectively at 30 and 75 min after biopsy. No differences in the measured variables were observed between the first and the second caffeine tests in the 34 patients susceptible to malignant hyperthermia. The first caffeine test was found to be positive in all of the 22 patients susceptible to malignant hyperthermia. However, in eight patients, the second caffeine test was negative and the muscle fibers were found to be significantly depolarized. Resting membrane potential was -73.4 +/- 7.9 mV before the first caffeine test and -65.8 +/- 8.8 mV before the second test. We suggest that when time-induced partial depolarization of malignant hyperthermia susceptible fibers occurs, fibers may become less sensitive to caffeine. PMID- 1734770 TI - Lecture practices in United States anesthesiology residencies. AB - We obtained data on lecture practices from 100 of the 110 university-affiliated anesthesiology residency programs certified in the United States in 1988. Of these residency programs, 36% had a majority of their lectures before the operating room schedule began, 57% had no lectures at all in this early time slot, and 78% had morning lectures at least once a week in conjunction with a delayed operating room start. Seventy-one percent of programs had one or more afternoon lectures each week. An attendance of more than 80% was reported in 66% of the programs for morning lectures and in 50% of the programs for afternoon lectures, which is a significant difference. Aggregate pass rates on the American Board of Anesthesiology written examinations in 1987 and 1988 correlated significantly with morning-lecture attendance, but not with afternoon-lecture attendance, number of lecture days per week, or mandatory lecture attendance. These findings suggest the need for further study and definition of the role of lectures in resident education in anesthesiology. PMID- 1734771 TI - Anesthesiology journals, 1992. PMID- 1734772 TI - Anesthetic management for magnetic resonance imaging: problems and solutions. PMID- 1734773 TI - Clinical use of magnesium infusions in anesthesia. PMID- 1734774 TI - Succinylcholine-induced prolonged apnea in a 3-week-old newborn: treatment with human plasma cholinesterase. PMID- 1734775 TI - Intravenous regional block using ketorolac: preliminary results in the treatment of reflex sympathetic dystrophy. PMID- 1734776 TI - Influence of anesthesia on the threshold of pacing-induced ischemia. AB - Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/ 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow. PMID- 1734777 TI - Continuous epidural infusion of bupivacaine and fentanyl for erythromelalgia in an adolescent. PMID- 1734778 TI - Acute and long-term benefits of iliac crest donor site perfusion with local anesthetics. PMID- 1734779 TI - Massive intraoperative pulmonary embolism: diagnosis with transesophageal two dimensional echocardiography. PMID- 1734780 TI - Venous air embolism during radical retropubic prostatectomy. PMID- 1734781 TI - An unusual complication of pulmonary artery catheterization. PMID- 1734782 TI - Bronchial obstruction by transesophageal echocardiography probe in a pediatric cardiac patient. PMID- 1734783 TI - Difficult endotracheal intubation in a patient with tumoral calcinosis. PMID- 1734784 TI - Anesthetic care of patients with Crigler-Najjar syndrome. PMID- 1734785 TI - End-systolic pressure-volume relationship and arterial elastance: the optimal method to evaluate myocardial contractile effects of anesthetic agents? PMID- 1734786 TI - Sacrococcygeal teratoma and venous shunting through a tumor: biological evidence. PMID- 1734787 TI - Anaphylactic reactions during anesthesia. PMID- 1734788 TI - Bleeding diathesis after perioperative ketorolac. PMID- 1734789 TI - Bleeding diathesis after perioperative ketorolac. PMID- 1734790 TI - A potential complication of lightwand-guided intubation. PMID- 1734791 TI - Ophthalmic surgery and vomiting--an ancient problem. PMID- 1734792 TI - Is the cardiovascular response to electroconvulsive therapy due to the electricity or the subsequent convulsion? PMID- 1734793 TI - Electrocardiographic R-wave changes during cardiac surgery. AB - The diagnostic accuracy of exercise electrocardiography has been improved by incorporation of R-wave gain factor to correct the measured ST-segment changes. If marked changes in R-wave amplitude occur in individual patients during cardiac operations, a similar gain factor correction may improve the intraoperative diagnosis of myocardial ischemia. This investigation was designed to determine the frequency and magnitude of intraoperative V5 R-wave amplitude changes during cardiac operations. Electrocardiograms were recorded from 83 patients while patients were awake, anesthetized (baseline), after placement of the Favaloro and Canadian sternal retractors, and at end-operation. Compared with baseline values, placement of the Canadian sternal retractor was associated with a reduction in V5 R-wave amplitude from 15 +/- 1 to 10 +/- 1 mm (mean +/- SEM), in V5 S-wave amplitude from 3.5 +/- 0.4 to 1.7 +/- 0.3 mm, and in absolute ST-segment deviation from 0.50 +/- 0.04 to 0.39 +/- 0.05 mm. Changes in V5 R-wave amplitude were correlated with changes in ST-segment deviation in patients with baseline ST segment deviations greater than or equal to 0.5 mm (r = 0.55, P = 0.0004, n = 37). Changes associated with the Favaloro retractor and the respiratory cycle were less marked. However, the V5 R-wave amplitude was decreased from 15 +/- 1 to 9 +/- 1 mm at end-operation. In conclusion, sternal spreading with the Canadian retractor was associated with marked reductions in V5 R- and S-wave amplitudes and ST-segment deviations. Marked changes in V5 R-wave amplitude persisted after sternal closure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734794 TI - A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass. AB - Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng.kg-1.min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 +/- 0.12 (mean +/- SEM) to 2.74 +/- 0.12 L.min-1.m-2; likewise, placebo improved cardiac index from 2.51 +/- 0.15 to 2.74 +/- 0.15 L.min-1.m-2. Mean arterial blood pressure increased with calcium from 74 +/- 2 to 82 +/- 3 mm Hg compared with a placebo change of 74 +/- 2 to 76 +/- 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 +/- 0.15 to 2.92 +/- 0.22 L.min-1.m-2, whereas in the placebo group it decreased from 2.86 +/- 0.13 to 2.78 +/- 0.12 L.min-1.m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion. PMID- 1734795 TI - Effect of alpha-stat versus pH-stat strategy on oxyhemoglobin dissociation and whole-body oxygen consumption during hypothermic cardiopulmonary bypass. AB - To determine whether alpha-stat or pH-stat strategy should be used, 20 patients undergoing coronary artery bypass grafting during moderate hypothermic hemodilutional cardiopulmonary bypass were studied. The carbon dioxide management during bypass was randomly done according to alpha-stat strategy in 10 patients (i.e., temperature-uncorrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4) and according to pH-stat strategy in the other 10 patients (i.e., temperature-corrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4). In both groups, when the central venous temperature was stable at 26.5 +/- 2.5 degrees C, the perfusion flow was altered sequentially from 2.4 to 1.8 and 1.2 L.min-1.m-2. The mixed venous oxyhemoglobin saturation at the different perfusion flows was monitored by the Oxy-Stat meter and was correlated with the corresponding mixed venous oxygen tension to construct an oxyhemoglobin dissociation curve. Also, the whole-body oxygen consumption at the different perfusion flows was computed. The whole-body oxygen consumption and the oxyhemoglobin dissociation were not significantly different between the alpha stat and the pH-stat groups. In both groups, the dissociation curve is shifted to the left, but the oxygen consumption per unit time does not significantly change despite decreasing the perfusion flow from 2.4 to 1.2 L.min-1.m-2. The results suggest that oxygen delivery is not impaired during moderate hypothermic cardiopulmonary bypass independent of whether alpha-stat or pH-stat strategy is used. PMID- 1734796 TI - Comparison of thromboxane synthetase inhibitor and methylprednisolone effects on protamine responses in dogs. AB - Neutralization of heparin anticoagulation by protamine produces catastrophic hemodynamic reactions in some patients. Using a canine model, we tested effects of thromboxane synthetase inhibition (CGS-13080) and glucocorticoid pretreatment on the cardiorespiratory effects of protamine. In control dogs, protamine decreased mean arterial pressure and cardiac output and increased mean pulmonary artery pressure, systemic and pulmonary vascular resistances (SVR, PVR), and airway pressure. Both CGS-13080 and methylprednisolone ameliorated some effects of protamine. CGS-13080 infusion decreased mean pulmonary artery pressure, SVR, and airway pressure after protamine injection relative to controls. Cardiac output and PVR were unaffected by the drug, whereas the decrease in mean arterial pressure was prolonged. Plasma thromboxane A2 metabolite (TXB2) concentrations were lower and prostacyclin metabolite (6-keto PGF1 alpha) concentrations were higher compared with that of controls. These experiments support a role for TXA2 in the response to protamine. Methylprednisolone pretreatment produced larger cardiac output and lower airway pressure after protamine injection compared with controls. Mean arterial pressure was improved, but not significantly. Mean pulmonary artery pressure, SVR, and PVR were not different from that of controls; TXB2 and 6-keto PGF1 alpha were unaffected. The effects of methylprednisolone appear unrelated to arachidonic acid metabolism, as TXB2 and 6-keto PGF1 alpha levels were unaffected. PMID- 1734797 TI - Transcatheter closure of atrial septal defects: hemodynamic complications and anesthetic management. AB - Transcatheter closure of atrial septal defects using a double-umbrella (clamshell) device can now be performed during an overnight hospital stay with little morbidity and no mortality. The initial 2-yr experience with anesthetic care for the procedure was collected and subsequently analyzed. Primary anesthetic care was given in 118 cases and urgent anesthetic intervention was required in another four cases. Anesthesia with spontaneous ventilation in patients with unprotected airways using intravenous ketamine and midazolam (average cumulative doses 1.4 and 0.17 mg.kg-1.h-1, respectively) was used in 93 cases (77%); mean maximum PaCO2 value was 41 +/- 6 mm Hg. In 29 patients (23%) tracheal intubation and muscle paralysis were used to facilitate control of airway and ventilation. Anesthetic-related complications occurred in three patients: ventilatory compromise developed in two patients in the spontaneous ventilation group and one patient experienced awareness during endotracheal anesthesia with paralysis. Procedural complications that altered anesthetic management were more frequent, including embolization of the clamshell device requiring surgical retrieval in two of six embolizations, intracardiac air embolization (four cases), tricuspid regurgitation (one case), device malplacement requiring late operation (one case), and transient brachial plexus injury (three cases). Anesthesia for transcatheter atrial septal defect closure allows precise device placement, prompt control of hemodynamic complications, and transesophageal echocardiographic monitoring of device placement. Although general anesthesia with spontaneous ventilation using ketamine and midazolam was usually safe and effective, tracheal intubation for control of airway and ventilation was sometimes necessary for safety and for optimal operating conditions. Familiarity with transcatheter closure techniques and close communication with the catheterization team is essential to minimize and treat associated complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734798 TI - Electrocardiographic changes during cesarean section under regional anesthesia. AB - To determine electrocardiographic changes and whether myocardial ischemia occurs during cesarean section, electrocardiograms were recorded continuously using Holter monitoring in 25 patients undergoing elective cesarean section under either spinal or epidural anesthesia. In addition, in 13 of the patients, two dimensional precordial echocardiography was carried out before and during cesarean section. ST segment depression suggestive of myocardial ischemia occurred in 16 patients including 8 of the 13 with echocardiograms. Wall motion remained entirely normal during episodes of ST segment depression. Patients in whom ST depression developed had significantly more rapid heart rates at delivery than those who did not experience ST depression. We conclude that ST segment depression is a common feature of the electrocardiogram during cesarean section under regional anesthesia and is not the result of myocardial ischemia. PMID- 1734799 TI - Pregnancy does not alter the threshold for lidocaine-induced seizures in the rat. AB - Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg.kg-1.min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 +/- 5.5, nonpregnant female = 12.1 +/- 4.9, pregnant female = 10.8 +/- 4.1 micrograms/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 +/- 6.3, nonpregnant female = 16.8 +/- 4.5, pregnant female = 16.7 +/- 4.2 micrograms/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats. PMID- 1734800 TI - Effect of ropivacaine and bupivacaine on uterine blood flow in pregnant ewes. AB - The effects of ropivacaine, a new amide local anesthetic, on uterine blood flow and fetal well-being were compared with those of bupivacaine in 10 chronically instrumented pregnant ewes. In random sequence, animals received two intravenous infusions of each drug. The low infusion rate regimens were chosen to result in clinically relevant maternal plasma concentrations of local anesthetics, whereas the more rapid rates of infusions were given to assess the safety of higher maternal drug concentrations. An epinephrine infusion was given to demonstrate the appropriateness of the animal model for the measurement of uterine blood flow. Maternal and fetal heart rates, arterial blood pressure, and the ewe's central venous pressure, intraamniotic pressure, and uterine blood flow were recorded continuously. Arterial blood samples were taken from mother and fetus at frequent intervals to determine acid-base status and local anesthetic concentrations. A total of 39 studies were performed. None of the infusions of either local anesthetic resulted in a significant decrease in uterine blood flow or deterioration in fetal condition. The mean maternal plasma concentrations at the end of infusions were as follows: ropivacaine low dose, 1.60 +/- 0.35 micrograms/mL; bupivacaine low dose, 1.55 +/- 0.15 micrograms/mL; ropivacaine high dose, 2.50 +/- 0.37 micrograms/mL; and bupivacaine high dose, 1.83 +/- 0.19 micrograms/mL. Epinephrine infusion resulted in a 25% decrease in uterine blood flow without adverse fetal effects. We conclude that neither ropivacaine nor bupivacaine, as administered in this study, led to any ill effects on uterine artery blood flow or fetal well-being. PMID- 1734801 TI - Attenuation of gastric effects of famotidine by preoperative administration of intravenous fluids. AB - Effects of preoperative administration of intravenous crystalloids on the gastric effects of famotidine were studied in 89 patients scheduled for elective surgery in the afternoon. Patients were randomly assigned to one of six groups. Groups P1, P2, and P3 received 2.0 mL of intramuscular saline (placebo) and groups F1, F2, and F3 received 20 mg of intramuscular famotidine 1 h before anesthesia. All patients fasted for 14-18 h before surgery. No fluid was administered to groups P1 and F1 preoperatively, whereas 500 mL of intravenous fluid was given to the other groups over a period of 4-5 h before anesthesia: a maintenance fluid with 10% glucose to groups P2 and F2, and lactated Ringer's solution without glucose to groups P3 and F3. After anesthetic induction, the stomach was aspirated using a nasogastric tube and volume and pH of the contents were measured. The gastric volume was significantly less in F2 (4.2 +/- 1.2 mL, mean +/- SEM) than in P1 (30.7 +/- 5.5 mL) (P less than 0.01) and in F3 (12.7 +/- 2.1 mL) than in P3 (26.8 +/- 4.4 mL) (P less than 0.05). There was no significant difference between P2 (23.4 +/- 4.6 mL) and F2 (17.5 +/- 3.5 mL). Mean pH values were significantly higher in F1 (6.82 +/- 0.48) than in P1 (3.21 +/- 0.72) (P less than 0.01). No significance was observed between P2 (3.65 +/- 0.62) and F2 (4.53 +/- 0.77), or P3 (3.17 +/- 0.81) and F3 (5.03 +/- 0.80).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734802 TI - Systemic and regional hemodynamics of isoflurane and sevoflurane in rats. AB - The authors studied the effects of sevoflurane and isoflurane on systemic hemodynamics and regional blood flow distribution (microsphere technique) in 15 rats during general anesthesia with intravenous chloralose and controlled ventilation. Inhaled anesthetics were applied to reduce mean arterial blood pressure (MAP) to 70 mm Hg (1.66 vol% sevoflurane and 0.96 vol% isoflurane) and 50 mm Hg (MAP 50; 3.95 vol% sevoflurane and 2.43 vol% isoflurane). Control recordings were obtained with intravenous chloralose only. At a MAP of 70 mm Hg, both anesthetics reduced heart rate, cardiac output, and systemic vascular resistance to a similar degree. Isoflurane decreased systemic vascular resistance markedly at a MAP of 50 mm Hg and thereby maintained cardiac output at higher levels than sevoflurane. The left ventricular rate-pressure product decreased comparably with both anesthetics. Cerebral blood flow increased dose-dependently with both inhaled anesthetics but to a greater degree with isoflurane. Total hepatic blood flow remained unchanged from control at a MAP of 70 mm Hg but decreased at a MAP of 50 mm Hg. This was due to reductions of hepatic arterial and portal venous tributaries. Renal blood flow was reduced with only the high concentrations of the anesthetics. Myocardial blood flow was reduced at all concentrations of volatile anesthetic; however, the decrease was less with isoflurane. This would indicate a more pronounced coronary vasodilation by isoflurane as the rate-pressure product, as a measure of the actual left ventricular oxygen demand, decreased by comparable degrees with both anesthetics. Our results indicate that sevoflurane and isoflurane (each approximately 0.7 MAC) have no dissimilar systemic and regional hemodynamic effects at a MAP of 70 mm Hg in this animal model. At higher concentrations (approximately 1.7 MAC), cerebral blood flow was more with isoflurane than with sevoflurane and was associated with a more pronounced vasodilation in the myocardium. PMID- 1734803 TI - Halothane- and enflurane-induced inhibition of phasic responses to carbachol in isolated guinea pig trachea. AB - Volatile anesthetics produce bronchodilatation by a combination of effects on the autonomic nervous system as well as direct effects on the airway smooth muscle. We sought to further explain the direct effects on airway smooth muscle by studying the effect of volatile anesthetics on the phasic and tonic components of the contractile response. The effects of 1.2%, 2.3%, and 4.3% halothane and 1.6%, 3.2%, 4.9%, and 8.7% enflurane on the phasic and tonic components of the contractile response to 10 microM carbachol and 40 mM KCl in isolated guinea pig trachea were determined using steady-state and kinetic analyses. No direct effect of either anesthetic on resting tension was observed. The peak tensions of the phasic responses to 10 microM carbachol were significantly inhibited by all concentrations of halothane and enflurane. The inhibition by enflurane was concentration-dependent and eliminated the phasic response at 8.7%. The peak tensions of the tonic responses to 10 microM carbachol were unaffected. The peak tensions of the responses to 40 mM KCl were unaffected by halothane but were significantly inhibited by 4.9% enflurane. The decay rate of the phasic response was unaffected by the anesthetics. The onset rate of the tonic response was significantly inhibited only by 8.7% enflurane, whereas halothane was without effect. The EC50 concentration for carbachol, as determined by cumulative concentration response curves, was increased by both 8.7% enflurane and 4.3% halothane. The results support the hypothesis that halothane and enflurane inhibit that portion of the contractile response to carbachol dependent on the release of intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734804 TI - Differential sensitivity of diabetic rat papillary muscles to negative inotropic effects of oxybarbiturates versus thiobarbiturates. AB - The negative inotropic effects of oxybarbiturates and thiobarbiturates were examined in papillary muscles isolated from streptozotocin-induced diabetic rats and in papillary muscles from age-matched control rats. The muscles from diabetic rats exhibited less negative inotropic responses to pentobarbital and secobarbital than the muscles from control rats. Conversely, the negative inotropic responses to thiopental and thiamylal were significantly enhanced in diabetic muscles. Differences in sensitivity to pentobarbital between control and diabetic muscles became less marked by treatment with ouabain or by lowering [Na+]o. Enhancement of the negative inotropic effect of thiamylal observed in diabetic muscles remained unchanged with these treatments. In both control and diabetic muscles, the negative inotropic effect of pentobarbital was completely reversed by increasing [Ca2+]o, but the effect of thiamylal was only partially reversed. These results suggest a difference in mechanism of action involved in establishment of the negative inotropic effects of oxybarbiturates vs thiobarbiturates. Oxybarbiturates appear to exclusively reduce the influx of extracellular Ca2+, whereas thiobarbiturates appear to affect Ca2+ movements at the Ca2+ storage sites in addition to the Ca2+ influx inhibition. PMID- 1734805 TI - The role of leukocyte-endothelial interactions in the accumulation of leukocytes in allergic inflammation. PMID- 1734806 TI - Fibroblasts and other structural cells in airway inflammation. PMID- 1734807 TI - Cellular inflammation in asthma: neutral proteases of mast cells. PMID- 1734808 TI - New insights into airway inflammation by endobronchial biopsy. PMID- 1734809 TI - The role of macrophages in the mechanisms of airway inflammation in asthma. PMID- 1734810 TI - Mechanisms of hyperresponsiveness: platelet-activating factor. PMID- 1734811 TI - Mechanism of aspirin sensitivity. PMID- 1734812 TI - Biologic effects of mast cell enzymes. PMID- 1734813 TI - Microvasculature and airway responses. PMID- 1734814 TI - Mechanisms of bronchial reactivity: the role of immunoglobulin E. PMID- 1734815 TI - Regulation of neurogenic inflammation by neutral endopeptidase. PMID- 1734816 TI - Persistent and latent viral infections in the pathology of asthma. PMID- 1734817 TI - Physical growth and socioeconomic background of Stockholm schoolchildren born in 1933-63. AB - Height, weight and body mass index (BMI) at aged 7, 10 and 13 years for samples of Stockholm schoolchildren born in 1933, 1943, 1953 and 1963 were analysed in relation to their socioeconomic background. In height there were significant socioeconomic differences for boys and girls born in 1933 and 1943 at the ages of 7 and 10 years; children from the lowest socioeconomic group were smaller. For the cohort born in 1953 there were, however, no socioeconomic differences in height--either for boys or for girls. For children born in 1963, socioeconomic differences in height appeared again, but mainly for the boys; boys in the lowest socioeconomic group were smaller. Significant weight differences between socioeconomic groups were for the boys found only in cohorts born in 1943 and in 1963 and for the girls born in 1933, 1943 and 1953. Socioeconomic differences in BMI were found for boys born in 1943, when the middle socioeconomic group had the lowest index, and for boys born in 1963 when the highest socioeconomic group had the highest index. For girls socioeconomic differences in BMI were only found for girls born in 1953 when the lowest group had the highest BMI. The main conclusions from the study were: socioeconomic differences in height formerly present in Stockholm schoolchildren born in 1933 and 1943 were levelled out for the children born in 1953, but reappeared again for children born in 1963--mainly for the boys; these socioeconomic height differences for the 1963 cohort were of about the same magnitudes as those for the cohort born in 1943 during the Second World War. The influence of socioeconomic background on the BMI of Stockholm schoolchildren born 1933-63 was not so marked. PMID- 1734818 TI - Prepubertal growth of boys and girls using data from the Edinburgh Longitudinal Growth Study. PMID- 1734819 TI - Population and sex differences in arm circumference and skinfold thicknesses among Indo-Pakistani children living in the East Midlands of Britain. AB - Arm circumference, triceps and subscapular skinfold thicknesses of 2224 Indo Pakistani children aged 3-10.9 years living in Nottingham and Leicestershire were measured. The children were classified into populations according to country of origin, and religion, prior to analysis. Significant between-population differences were shown for all three variables, the effect being stronger in males than in females. Sex differences in arm circumference and triceps skinfold thickness were greater than those found in the British reference populations, whilst the patterns of fat distribution differed from the British standards for all the Indo-Pakistani populations, male and female. PMID- 1734820 TI - Urban-rural differences in the growth of South African black children. AB - Urbanization is a major migratory process characteristic of developing countries. The majority of comparisons of the growth of urban and rural children from developed countries reflect greater heights and weights, and by implication health, of urban children. Urban-rural comparisons of South African black children are few in number and have concentrated on 'average' children, thereby omitting the factor of socioeconomic status. The present study compares two groups of urban children of high (n = 307) and average (n = 867) socioeconomic status and two groups of rural children. The rural children came from farm labourer's families (n = 392) and traditional subsistence farming environments (n = 420). The children ranged in age from 5 to 19 years. In general the well-off urban children were consistently, but not significantly, larger than all other groups and 'average' urban children were consistently and at times significantly smaller and lighter. The growth of the two rural groups fell between these extremes but were also consistently different in that the children of farm labourers were significantly lighter at all ages than children living in a traditional subsistence economy. It is concluded that the average urban environment in South Africa is not conducive to improved growth and health unless it is accompanied by an improved socioeconomic status. PMID- 1734821 TI - Serum protein polymorphisms (HP, TF, GC and PI) in four Iranian population samples. AB - A total of 960 individuals from four Iranian population samples (Tabriz, Tehran, Yazd, Mashhad) was typed for HP and for TF, GC and PI subtype polymorphism. Statistically significant intergroup heterogeneity in the distribution of allele frequencies was found only in the HP polymorphism. Comparisons with other Iranian populations suggest considerable ethnic differences with regard to the TF and GC subtype polymorphisms. Some rare alleles were observed in all four samples (Tabriz: GC*1C1; Tehran: PI*S: Yazd: PI*S; Mashhad: PI*Z). PMID- 1734822 TI - Physical growth of Chinese school children 7-18 years, in 1985. AB - Physical development in Chinese school children was analysed based on a national survey in 1985. Close to half a million children and adolescents, aged 7-18, from Han ethnic group and 27 minority ethnic groups were assessed for height, weight, sitting-height, chest circumference, biacromial and biiliac diameters. Growth in Han children was greater than that in minority ethnic group children. The growth differences among minority ethnic groups were large. Growth in urban children was greater than that in rural children except in a few age groups of girls. A significant difference in children's growth was found between northern and southern divisions of China, it being greater in the north. The growth curves of physical characteristics demonstrated systematic regularity. Finally, the results of this study were compared with research reports from other world literature. PMID- 1734823 TI - Body composition and body hydration in old age estimated by means of skinfold thickness and deuterium dilution. AB - In this study a group of 30 women and 30 men aged 60-90 years was examined. Body density was predicted from the sum of four skinfold thickness (SFT) as described by Durnin and Womersley (1974). Body composition, expressed as a percentage of total body weight as fat mass (FM) and fat free mass (FFM) was calculated by means of Siri's formula (Siri 1961). Total body water (TBW) was measured from the dilution of an oral deuterium dose and FFM calculated assuming a hydration of 73.2%. The FM% predicted from SFT showed a slight but not significant decreasing age trend from 28.3% to 25.4% in men, and from 40.3% to 37.8% in women. Body hydration (about 50% of body weight in men and 44% in women) remained constant throughout the age range. FFM obtained from TBW assuming a constant hydration of FFM, was found to be unchanged with age. FM% predicted from SFT was correlated with values obtained from TBW on an individual basis (R2 = 0.38; p less than 0.0001 in men and R2 = 0.31; p less than 0.002 in women), but the scatter was large. The Bland and Altman statistical analysis (Bland and Altman 1986) suggests that the discrepancy between the two estimates tends to be significantly more positive with increasing fatness of the subject. The assumption of a constant hydration of FFM between individuals and with advancing age was tested. The hydration of FFM was calculated as the ratio between TBW (from deuterium dilution) and FFM (estimated from SFT). The wide range of values (50% to 90%) suggests large inter-individual differences. The mean values were lower than commonly reported, and differed with age and sex. In men, FFM hydration steadily decreases with age from the 7th decade (70.2 +/- 7.7%) to the 10th decade (65.9 +/- 8.2%). Women showed higher average figures than those of men and a lower age associated decline (72.5% and 68.5% respectively). Our results suggest that FFM hydration decreases with age, and this indicates the need to develop age-related correction factors in order to derive FFM from TBW in an elderly population. PMID- 1734824 TI - Salivary testosterone concentration of Aymara men native to 3600 m. AB - This paper explores the possibility that variation in the normal physiological range of testosterone concentration modulates men's adaptation to hypobaric high altitude hypoxia through stimulating haemoglobin production and/or causing respiratory disturbances and exacerbated hypoxaemia during sleep. These effects of testosterone are observed clinically at sea level and have potentially opposing consequences at high altitude, the former perhaps enhancing and the latter diminishing the effectiveness of adaptations to hypoxia. Seventeen young (average age 27 years) and 22 older (average age 57 years) healthy adult high altitude native Aymara men tested at 3600 m have average morning salivary testosterone concentrations of 282 and 241 pmol/l, respectively. The 31 urban men of both age groups have higher testosterone concentrations than the eight rural men and have mean haemoglobin concentrations significantly 0.7-1.0 g/dl higher within the normal high-altitude range, consistent with known effects of testosterone at sea level. Older urban men have slightly more frequent respiratory disturbances during sleep, associated with significantly greater hypoxaemia. There appear to be modest benefits to testosterone concentrations in the upper end of the observed range; however, the direction of these responses towards more haemoglobin production and more hypoxaemia during sleep of older men suggests the hypothesis that very high testosterone concentrations such as those in the upper ranges of sea level values could compromise adaptation to high altitude, particularly among older men. PMID- 1734825 TI - The anthropometric history of Pittsburgh and Allegheny County, Pennsylvania, 1890 1945. AB - A positive relationship has been found between the height and socioeconomic status of Pittsburgh and Allegheny County residents born between 1890 and 1945. Generally, the higher their socioeconomic status, the higher was their stature. However, the relationship gradually became weaker and by World War II was nearly negligible, because the growing economy was able to meet the nutritional and medical needs of the population better. Inequality still existed, but it manifested itself less in necessities than in the area of education, amenities and luxury. The Great Depression did not seem to have an adverse effect on the biological well-being of the population as a whole, as most people were able to maintain the rising standard of necessities while sacrificing amenities and luxury. PMID- 1734826 TI - Further observations on diurnal variation in standing height. AB - A total of 328 daily assessments of standing height were made on one boy between the ages of 12.83 and 13.95 years; 292 of these were replicates to establish reliability of measurement. On 300 days, measurements were taken in the morning within 1/2 h of rising (which varied between 0700 and 1100 h) and repeated before bed on the same day, between 2100 and 2300 h. The standard error of measurement from 292 duplicate measurements was 0.12 cm. A mean of 0.98 +/- 0.2 cm decrease in stature occurred during the course of the day. A similar decrease was found on three occasions after 2-3 h naps. PMID- 1734827 TI - Primary squamous cell carcinoma originating in congenital cysts of the liver. Report of a case and review of the literature. AB - An 82-year-old woman developed a well-differentiated squamous cell carcinoma that apparently arose in two discrete congenital cysts of the liver. Both cysts were lined predominantly by stratified squamous epithelium with extensive areas of dysplasia and foci of transition to in situ carcinoma and overt exophytic and infiltrating squamous cell carcinoma. A third intrahepatic cyst was lined entirely by bile duct-type epithelium and contained no tumor. The liver was massively infiltrated by the carcinoma, and there were metastases to the lymph nodes, lung, and bone marrow. Since a search for an alternative primary tumor site was unrevealing, the authors interpret this as a unique case of primary squamous cell carcinoma originating in congenital cysts of the liver. PMID- 1734828 TI - A clinical laboratory management elective for pathology residents. AB - Many practicing pathologists, particularly those in private settings, function as managers. Their responsibilities may not only involve directing the successful activities of laboratory personnel, but often require a level of accountability to hospital administrators or business managers. Traditional training programs focus on technical competency and devote little time, if any, to preparing their graduates for the management aspects of their careers. In response to this need, a 1-month elective was designed for senior pathology residents at the University of Utah, Salt Lake City. The cumulative experiences of a large academic pathology department and its successful commercial laboratory venture provided a real-world supplement to a curriculum founded in basic business management principles. PMID- 1734829 TI - The new HLA. AB - The application of molecular genetics and biochemical techniques to the study of the HLA system over the past few years has resulted in tremendous advances in our knowledge of this area of the human genome. In this article, we describe the "new HLA" that has been pieced together recently through the combined efforts of molecular geneticists, biochemists, and HLA serologists, as well as developments in attempts to elucidate the associations of HLA antigens and disease. PMID- 1734830 TI - Pathologic correlation in mammographically directed breast biopsies. AB - In a series of 1137 diagnostic breast biopsy specimens in a 2-year period, nearly half (n = 534) underwent specimen mammography. Calcifications were found in 48% of the specimen mammograms. In a quarter of the cases, calcification was a marker either for carcinoma or a significant precursor lesion. Moreover, in the majority of these malignancies, calcifications were markers of preinvasive carcinoma. In another quarter of cases, some form of proliferative ductal hyperplasia accounted for calcifications, and in the remainder, cysts and miscellaneous other conditions accounted for calcifications. The yield of malignancy was much lower in noncalcified specimens (12%). A nodular or asymmetric density proved to be a fibroadenoma in 30% of cases. However, the majority of cases had less well defined changes, probably representing some form of lobular fibrosis. We found submission of a duplicate specimen mammogram with the breast biopsy specimen to pathology to be a significant adjunct to correlation. The abnormal area is marked on the mammogram by the radiologist for the pathologist. This is particularly helpful for localizing noncalcified stromal abnormalities. Calcifications are most easily and reliably isolated by serial slicing and performing another radiograph of the slices. PMID- 1734831 TI - Pulmonary metastases of colonic carcinoma. Distinction from pulmonary adenocarcinoma. AB - Pulmonary metastases may develop in patients with colonic carcinoma. Histopathologic separation of a solitary colonic metastasis from a primary pulmonary adenocarcinoma may be problematic. With the use of a polyclonal antibody to carcinoembryonic antigen, a monoclonal antibody to cytokeratin (CAM 5.2), and a monoclonal carcinoembryonic antigen antibody (D-14), we compared 23 colonic carcinomas metastatic to the lung with 24 primary pulmonary adenocarcinomas. Both carcinomas manifested similar histologic features. However, foci of "dirty necrosis" were common in all but one of the colonic neoplasms, and foci were observed in only four of the primary lung carcinomas. The polyclonal carcinoembryonic antigen antibody did not distinguish metastatic colonic carcinoma from primary pulmonary adenocarcinoma. All colonic tumors stained with D-14, while three primary pulmonary adenocarcinomas stained diffusely, and eight stained focally. Staining with D-14 will not absolutely distinguish colonic from pulmonary adenocarcinoma. However, positive D-14 staining and the presence of dirty necrosis should identify most colonic carcinomas. True-negative D-14 staining practically excludes a colonic origin. PMID- 1734832 TI - Measurement of glomerular basement membrane thickness and its application to the diagnosis of thin-membrane nephropathy. AB - Morphometry is a valuable diagnostic aid when the glomerular basement membrane is suspected of being abnormally thin. Determination of overall width by the harmonic mean method has been described in detail. Results were given of measurements in 20 control subjects with histologically normal basement membranes and 41 allograft kidneys. Mean +/- 1.5 SDs of a series was found to be the most useful empiric guide to basement membrane widths. It was confirmed that the membrane was thinner in females than in males. The lower end of the respective mean +/- 1.5 SDs range overlapped with thicknesses that occurred in "thin membrane nephropathy" in women but not in men, although the threshold width below which hematuria was liable to occur was similar, at approximately 340 nm, in both sexes. It is suggested that the higher incidence of symptomatic thin-membrane nephropathy in females is related to their normally thinner glomerular basement membranes, in the context of the common threshold level. Other histologic findings, and the clinical picture, remain relevant to the diagnosis of thin membrane diseases. PMID- 1734834 TI - Prolonged storage of tissues at low temperatures does not preclude their use for ultrastructural studies. AB - A cost-effective method for electron microscopic study of snap-frozen surgical specimens is described. The method is available to any surgical pathology laboratory equipped with a deep freezer and allows the performance of ultrastructural observations on archival material. PMID- 1734833 TI - Renal microvascular features of hypertension in Japan, Guatemala, and the United States. AB - The finding of benign arteriolar nephrosclerosis at autopsy usually implies the prior existence of essential hypertension. It was found in this study that minor degrees of incipient nephrosclerosis in young people can be shown to correlate with seemingly trivial blood pressure elevations. In this study, autopsy tissues were used to assess the magnitude of early nephrosclerosis in five population groupings. A comparison of males in Tokyo, Japan, Guatemala, and New Orleans, La (blacks and whites); and females in Tokyo revealed significant differences among these populations. Blacks exceeded whites in New Orleans in the magnitude of incipient nephrosclerosis in all 10-year age groups from 15 through 24 years to 45 through 54 years. Guatemalan males were, on average, less affected than New Orleans whites in all age groups. The data for all males (age range, 15 through 54 years) in Tokyo revealed little difference in nephrosclerosis from those in New Orleans whites. Blood pressure data were obtained from reports of cross sectional surveys in these five populations. Blood pressure in males varied across age x race subgroups in close parallel with nephrosclerosis (r = .90), implying that variation in blood pressure among groups of subjects is strongly nephrosclerosis linked, even at very young ages; findings for Tokyo females were aberrant in this correlation. The results suggest that the lifelong progression toward the hypertensive state begins in childhood, and that these beginnings are measurably in the population averages of both nephrosclerosis and blood pressure elevations. Moreover, population differences in these two commensurate measures of the early precursors of hypertension were found to be well established by the ages of 15 through 24 years and were sustained at least into the ages of 45 through 54 years. The years of adolescence are here brought under suspicion of special importance in setting the lifelong course toward the hypertensive state. PMID- 1734835 TI - Lectin histochemistry of human fetal notochord, ecchordosis physaliphora, and chordomas. AB - Lectin histochemical studies of human fetal notochord, ecchordosis physaliphora, and eight chordomas were performed. Ecchordosis physaliphora and eight chordomas were stained with Ricinus communis type I, Canavalia ensiformis, Triticum vulgaris, and Limax flavus. Ricinus communis type I, T vulgaris, and L flavus reacted with both tumor cells and the extracellular mucinous matrix, while C ensiformis mainly reacted with the cytoplasm of tumor cells. Thus, tumor cells were most recognizable with the C ensiformis stain. After neuraminidase treatment, ecchordosis physaliphora and chordomas invariably showed positivities for Arachis hypogaea. The lectin-binding patterns of chordomas closely reflected those of the human fetal notochord. Chordomas were completely sialylated regardless of either the clinical course or histopathological findings. Among the eight lectins, C ensiformis heavily labeled chordoma cells but not extracellular space. This was probably because asparagine-linked N-glycosylation was active in the chordomas, while the high-mannose-type oligosaccharides were apt to remain in the cytoplasm. PMID- 1734836 TI - Predicting the effect of hemolysis on measured creatine kinase: a caveat. PMID- 1734837 TI - Proteinaceous lymphadenopathy and the kidney. PMID- 1734838 TI - Automated measurement of red blood cell microcytosis and hypochromia in iron deficiency and beta-thalassemia trait. AB - Some routine red blood cell (RBC) measurements and indexes (count, mean volume, volume dispersion, and mean hemoglobin [HGB] concentration) can be used to differentiate iron deficiency from heterozygous beta-thalassemia. A number of formulas that incorporate two or more of these measurements have been described to amplify such differences. The H*1 hematology analyzer directly measures volume and HGB concentration of individual RBCs. We have assessed the diagnostic usefulness of conventional and new RBC measurements provided by the H*1 on a learning data set that comprised 119 patients with iron deficiency and 172 patients with beta-thalassemia trait, both untreated and uncomplicated. The most striking finding was the inverse behavior of percentages of microcytes (volume, less than 60 fL) and hypochromic RBCs (HGB concentration, less than 280 g/L) in the two conditions. In 162 of 172 patients with beta-thalassemia trait, the percentage of microcytes (mean, 33.1%; central 95th percentile range, 9.2% to 54.5%) was higher than the percentage of hypochromic RBCs (mean, 13.9%; central 95th percentile range, 1.7% to 24.7%). In 105 of 119 patients with iron deficiency, on the contrary, the percentage of hypochromic cells (mean, 34.6%; central 95th percentile range, 9.7% to 73.1%) was higher than the percentage of microcytes (mean, 12.8%; central 95th percentile range, 1.7% to 29.6%). The ratio between the percentage of microcytes and the percentage of hypochromic cells provided by the H*1 (microcytic-hypochromic ratio) was useful in differentiating the two types of microcytic anemia: with the use of a discriminant value of 0.9, the discriminant efficiency of the microcytic-hypochromic ratio was 92.4% (95% confidence interval, 88.8% to 95.2%), higher than that of the five previously described discriminant formulas and simple RBC measurements. When assessed on a test data set that comprised 149 unselected cases of microcytic anemia, a microcytic-hypochromic ratio lower than 0.9 demonstrated high sensitivity (94.0%), specificity (92.3%), and predictive value (94.0%) for the presence of iron-deficient erythropoiesis in patients with isolated iron deficiency, polycythemia vera treated by phlebotomy, and iron deficiency complicating heterozygous thalassemia. In conclusion, our results showed that iron-deficient erythropoiesis is characterized by the production of RBCs with a severely decreased HGB concentration, while microcytes of beta-thalassemia trait are generally smaller, with a more preserved HGB concentration. Such properties, as assessed by the H*1 hematology analyzer, are very useful in distinguishing these two common types of microcytic anemia. PMID- 1734839 TI - Pseudopolycythemia, pseudothrombocytopenia, and pseudoleukopenia due to overfilling of blood collection vacuum tubes. AB - A patient blood sample with an unexpectedly high hemoglobin level, high hematocrit, low white blood cell count, and low platelet count was recognized as being spurious based on previously available data. Repeated testing of the original sample showed a gradual return of all parameters to expected levels. We provide evidence that the overfilling of blood collection vacuum tubes can lead to inadequate sample mixing and that, in combination with the settling of the cellular contents in the collection tubes, can result in spuriously abnormal hematological parameters as estimated by an automated method. PMID- 1734840 TI - Fatal neonatal pneumonia caused by adenovirus type 35. Report of one case and review of the literature. AB - A 3680-g term male neonate developed bilateral bronchopneumonia at 9 days of age. The labor, delivery, and immediate postnatal period had been unremarkable. Despite standard antibiotic therapy, the patient progressed to respiratory failure and died 4 days later. Adenovirus particles were found in oropharyngeal secretions 1 day prior to death. Autopsy revealed an extensive necrotizing bronchiolitis and alveolitis with frequent "smudge cells." Adenovirus was identified by culture, electron microscopy, and in situ DNA hybridization. The adenovirus was serotyped as type 35, which, to our knowledge, has not been previously described in neonatal adenovirus pneumonia. PMID- 1734841 TI - Pheochromocytoma producing multiple vasoactive peptides. AB - Pheochromocytomas may produce several vasoactive peptides. We studied a 39-year old man who presented with paroxysmal flushing and abdominal pain with normal blood pressure. Laboratory and radiologic studies established the diagnosis of right adrenal pheochromocytoma, and histologic and ultrastructural examination showed the tumor to be a typical pheochromocytoma. Tissue culture yielded large quantities of norepinephrine and epinephrine. However, immunohistochemical studies, tissue assays, and in vitro cultures documented production of several peptides, including calcitonin gene-related peptide and vasoactive intestinal polypeptide in tumor cells. The patient has been asymptomatic after tumor resection. Production of multiple peptides by this tumor may account for the flushing and lack of hypertension, despite elevated catecholamine levels in this patient. PMID- 1734842 TI - History and current status of trauma scoring systems. PMID- 1734844 TI - Molecular biology: the message, its language, and the surgeon. PMID- 1734843 TI - Unnecessary operation? PMID- 1734845 TI - The making of a surgeon revisited. PMID- 1734846 TI - Catheter sepsis in short-bowel syndrome. AB - Catheter sepsis with catheter removal is an important problem in patients with short-bowel syndrome. We determined the incidence of catheter sepsis and the catheter salvage rate in 20 pediatric patients with short-bowel syndrome. To evaluate the intestine as a source and translocation as the pathophysiologic mechanism for catheter sepsis, we identified the sepsis organisms, compared them with the fecal flora, and used mesenteric lymph node cultures to document translocation. The incidence of catheter sepsis was significantly higher in patients with short-bowel syndrome than in patients without short-bowel syndrome (7.8 vs 1.3 per 1000 catheter days). Overall catheter salvage was 42% and was highest in gram-negative sepsis (71%). Enteric organisms were responsible for 62% of cases of catheter sepsis in patients with short-bowel syndrome vs 12% in patients without short-bowel syndrome. Anaerobes were strikingly absent in 25 of 28 stool cultures. The sepsis organism was identified in the fecal flora in 19 of 28 cases. The dominant fecal organism or yeast was the septic organism in 12 of these 19 cases and was isolated in three of four mesenteric lymph node cultures. Our findings support translocation as a mechanism in catheter sepsis in patients with short-bowel syndrome. PMID- 1734847 TI - Alterations in intestinal permeability after thermal injury. AB - Alterations in intestinal permeability have been postulated to occur after thermal injury. We evaluated the status of intestinal permeability during the first 2 postburn weeks in 15 subjects by measuring the differential excretion of enterally administered lactulose and mannitol. The mean age and burn size of the patients were 32.7 +/- 3.6 years and 53.3% +/- 5.1% of the total body surface area, respectively. Ten healthy volunteers were also studied. The lactulose mannitol excretion ratio was 0.159 +/- 0.017 for the patients and 0.017 +/- 0.003 for controls. The increased ratio did not correlate with burn size or postburn day. Patients who developed significant clinical infections during their first 2 postburn weeks had lactulose-mannitol ratios on postburn day 2 that were significantly higher than those of controls and patients who did not develop infections. This suggests a relationship between susceptibility to infection and early alterations in intestinal permeability. PMID- 1734848 TI - Liver nonparenchymal cells are stimulated to provide interleukin 6 for induction of the hepatic acute-phase response in endotoxemia but not in remote localized inflammation. AB - It has been postulated that Kupffer cells provide signals that regulate hepatocyte responses in sepsis and inflammation. Although in vitro data support such a hypothesis, to our knowledge, no in vivo evidence has been reported. We injected rats with lipopolysaccharide intraperitoneally to simulate sepsis or turpentine intramuscularly to mimic localized inflammation. Both treatments are known to induce the hepatic acute-phase response. Liver nonparenchymal cells and hepatocytes were isolated and placed in culture. Hepatocyte fibrinogen synthesis was measured as an indication of interleukin 6 exposure, while nonparenchymal interleukin 6 production was measured directly. Both lipopolysaccharide and turpentine stimulated a sharp increase in hepatocyte fibrinogen synthesis (turpentine greater than lipopolysaccharide). However, only lipopolysaccharide injection was associated with increased nonparenchymal cell interleukin 6 synthesis. Increased circulating levels of interleukin 6 could be found only after lipopolysaccharide injection. In addition, tumor necrosis factor synthesis was enhanced by lipopolysaccharide but not turpentine. Our data show that nonparenchymal cells are stimulated to provide the interleukin 6 signal to hepatocytes in endotoxemia but not in remote localized inflammation, even though both treatments stimulate the hepatic acute-phase response. Our findings support paracrine functions for liver sinusoidal cells in certain septic states. PMID- 1734849 TI - Analysis of infectious complications occurring after solid-organ transplantation. AB - To improve our understanding of posttransplant infections, we analyzed bacterial, viral, fungal, parasitic, and other infections in 604 consecutive recipients of kidney (n = 518), kidney-pancreas (n = 82), kidney-liver (n = 3), or kidney-islet (n = 1) allografts (355 cadaveric, 14 living-unrelated, 235 living-related donors) who also received cyclosporine, azathioprine, and prednisone immunosuppression. Recipients of cadaveric grafts received additional induction immunosuppression (antilymphocyte globulin or murine monoclonal antibody OKT3). Rejection episodes were treated with high-dose steroids, and either antilymphocyte globulin or OKT3 was administered when clinically indicated. Perioperative antibiotics and posttransplant prophylactic acyclovir sodium or ganciclovir sodium, trimethoprim-sulfamethoxazole, and clotrimazole or nystatin (Mycostatin) were administered to all recipients. Two hundred thirteen patients (35.3%) were found to have had no identifiable infections, while 391 (64.7%) had either isolated bacterial (97 [16.1%]), viral (53 [8.8%]), or fungal (34 [5.6%]) infections or combination (concurrent or sequential) infections with bacterial plus viral (46 [7.6%]), bacterial plus fungal (66 [10.9%]), viral plus fungal (20 [3.3%]), bacterial plus viral plus fungal (64 [10.6%]), or bacterial plus viral plus fungal plus parasitic (11 [1.8%]) pathogens in the posttransplantation period. Renal allograft survival (percentage, actuarial method) was diminished in patients with infections at both 1 year (91% vs 83%) and 3 years (81% vs 76%) after transplantation, as was actuarial patient survival (1 year, 97% vs 92%; 3 years, 93% vs 88%). We conclude that infection remains a major cause of both patient demise and allograft loss following successful solid-organ transplantation. PMID- 1734850 TI - Ibuprofen improves survival but does not ameliorate increased gut mucosal permeability in endotoxic pigs. AB - Intravenous lipopolysaccharide (LPS) decreases superior mesenteric arterial blood flow and increases ileal mucosal permeability in pigs. We tested the hypothesis that these phenomena can be ameliorated by pretreatment and posttreatment with ibuprofen. Pentobarbital-anesthetized immature swine were mechanically ventilated (fraction of inspired oxygen, 0.5) and infused with Ringer's lactate (RL) solution (0.8 mL/kg per minute). Animals in group RL (n = 10) received no other interventions. Animals in group RL + LPS (n = 15) were infused with LPS (50 micrograms/kg) from a time range equal to 0 through 60 minutes. Animals in group RL + LPS + ibuprofen (n = 10) were similarly infused with LPS, but in addition, they received ibuprofen (10 mg/kg at -30 minutes and 10 mg/kg per hour from -30 through 210 minutes). Intestinal permeability was assessed by measuring plasma-to lumen clearances of two hydrophilic probes (chromium 51-labeled edetic acid monohydrate [EDTA] and urea) and by expressing the results as a clearance ratio (CEDTA/CUREA). Survival was 100%, 67%, and 100% in groups RL, RL + LPS, and RL + LPS + ibuprofen, respectively. Among survivors only, CEDTA/CUREA increased significantly over time in both endotoxic groups, but not in nonendotoxic controls. Treatment with ibuprofen transiently blocked LPS-induced mesenteric hypoperfusion. These data indicate that mediators other than cyclooxygenase derived metabolites of arachidonic acid are responsible for the adverse effect of LPS on mesenteric permeability to hydrophilic solutes in this porcine model. PMID- 1734851 TI - Inhibitory effects of interleukin 6 on immunity. Possible implications in burn patients. AB - Certain disease states are associated with abnormal increases in the monokine interleukin 6. Increased levels of interleukin 6 have been demonstrated in serum from patients with burns and are associated with systemic increases in endotoxin levels. Using a murine in vitro experimental model, we have studied the effects of interleukin 6 on various measures of immunity. Our data indicate that levels equivalent to the concentrations found in serum of burn victims inhibit T-cell proliferation. The inhibitory effect is dose and time dependent, is specific for T cells, is not due to impairment of interleukin 2 production or of interleukin 2 receptor expression, and is dependent on macrophages. These data suggest that extraordinary increases in interleukin 6 levels may be related to impaired T-cell responses and to an increased susceptibility to infection in the patient with burns. PMID- 1734852 TI - Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. AB - Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated. Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight). Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later. Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours. Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release. Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice. Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage. PMID- 1734853 TI - The necessity and efficiency of wound surveillance after discharge. AB - A surgical wound surveillance program followed up 16,453 consecutive patients from 1983 through 1988. Patients were followed up for 30 days after operation, and 516 (35%) of the surgical wound infections first became manifest after discharge. In-hospital surveillance alone would have estimated the surgical wound infection rate to be 5.8% when the true rate was 8.9%. Infections that occurred after discharge were more likely in clean operations, in shorter operations, in obese patients, and in nonalcoholic patients. The probability that infections would begin after discharge was inversely associated with the duration of postoperative stay in the hospital. Postdischarge follow-up of patients who previously have undergone surgery is necessary to avoid underestimated of the infection rates and biases related to known risk factors. The most efficient time to survey patients appears to be at 21 days after the operation, at which time 90% of surgical wound infections have occurred. PMID- 1734854 TI - Guidelines for clinical care: anti-infective agents for intra-abdominal infection. A Surgical Infection Society policy statement. AB - Several antibiotics have been marketed for therapeutic use in intra-abdominal infection. Often, these agents do not provide a sufficient spectrum activity against both facultative and obligate anaerobic gram-negative organisms, or have certain toxic effects that would not otherwise support their use. Guidelines have been developed for selection of antibiotic therapy for intra-abdominal infections and are presented as a statement of the Surgical Infection Society endorsed by the Executive Council. These guidelines are restricted to infections derived from the gastrointestinal tract and deal with those microorganisms commonly seen in such infections. The recommendations are based on in vitro activity against enteric bacteria, experience in animal models, and documented efficacy in clinical trials. Other concerns regarding pharmacokinetics, mechanisms of action, microbial resistance, and safety were also used in the formation of these guidelines. For community-acquired infections of mild to moderate severity, single-agent therapy with cefoxitin, cefotetan, or cefmetazole or ticarcillin clavulanic acid is recommended. For more severe infections, single-agent therapy with carbapenems (imipenem/cilastatin) or combination therapy with either a third generation cephalosporin, a monobactam (aztreonam), or an aminoglycoside plus clindamycin or metronidazole is recommended. Regimens with little or no activity against facultative gram-negative rods or anaerobic gram-negative rods are not considered acceptable. PMID- 1734855 TI - Chronic pancreatitis beginning in childhood and adolescence. AB - We identified 10 patients with symptoms beginning before the age of 20 years in a group of 69 patients with proven chronic pancreatitis. Six of the 10 patients were women. There was a family history of pancreatitis in three patients and alcohol exposure in seven patients. Three patients were dependent on narcotics at the time of presentation. Six of the 10 patients had pancreatic duct dilatation to 10 mm or more in diameter during observation. These six patients underwent pancreaticojejunostomy, with clinical improvement in five patients. The median time of follow-up was 19 years from presentation. No patient developed diabetes and one developed malabsorption. Only three patients were free of pain, but four other patients had only mild episodes that rarely required hospital admission. One patient died of metastatic abdominal carcinoma of unknown origin 51 years after developing familial pancreatitis. Chronic pancreatitis beginning at a young age is sufficiently common to merit special awareness. It is compatible with prolonged survival, and pancreaticojejunostomy may help if the pancreatic duct reaches sufficient size. The disease does not seem to burn out with time. PMID- 1734856 TI - Hypertonic saline treatment of uncontrolled hemorrhagic shock at different periods from bleeding. AB - Hypertonic saline has been recently recommended for treatment of patients in hemorrhagic shock. Infusion of hypertonic saline at different periods in cases of uncontrolled hemorrhagic shock was studied in rats. The animals were divided into six groups: in group 1 uncontrolled hemorrhagic shock was induced by tail resection and no hypertonic saline was administered; in group 2 hypertonic saline was administered 5 minutes after shock was induced; in group 3 hypertonic saline was administered 15 minutes after shock was induced; in group 4 hypertonic saline was administered 30 minutes after shock was induced; in group 5 hypertonic saline was administered 60 minutes after shock was induced; and in group 6 hypertonic saline was administered 120 minutes after shock was induced. Tail resection in rats in group 1 was followed by a mean +/- SEM bleeding of 2.7 +/- .03 mL in 5 minutes. Infusion of hypertonic saline after 5 and 15 minutes resulted in additional bleeding of 6.3 +/- 1.0 mL and 3.8 +/- 0.5 mL, respectively, and a drop in mean arterial pressure to 36 +/- 8 mm Hg and 56 +/- 9 mm Hg, respectively. Mortality was 80% in group 2 and 53% in group 3. Infusion of hypertonic saline 30 and 60 minutes after shock was induced did not alter bleeding, mean arterial pressure, or survival. Infusion of hypertonic saline within 15 minutes of hemorrhagic shock resulted in increased bleeding, hypotension, and early death. Infusion 30 minutes or later did not alter these variables. This potential danger of early hypertonic saline therapy should be considered in the treatment of patients in trauma. PMID- 1734857 TI - Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase). AB - The cDNA for prostaglandin endoperoxide synthase (cyclooxygenase) was cloned from human platelets by the polymerase chain reaction amplification method, and the primary structure of the enzyme was deduced from the nucleotide sequence. The enzyme was composed of 599 amino acids including 23-amino acid signal sequence, and the calculated molecular weight of the mature protein was 65,995. The enzyme was immunoaffinity-purified from human platelets. The N-terminal amino acid sequence determined by Edman degradation was Ala-Asp-Pro-Gly-Ala-Pro-Thr-Pro-, and the result confirmed the primary structure of the enzyme, which was deduced from the cDNA sequence. PMID- 1734858 TI - Leupeptin and ammonium chloride inhibit intrinsic factor mediated transcytosis of [57Co]cobalamin across polarized renal epithelial cells. AB - The [125I] intrinsic factor (IF) mediated transcytosis of [57Co]Cyanocobalamin (Cbl) by polarized opossum kidney cells was inhibited (greater than 80%) by preincubation of the cells with lysosomotropic agents leupeptin or ammonium chloride. Inhibition of Cbl transcytosis resulted in the intracellular accumulation of both [125I]IF (48 kDa) and [57Co]Cbl. Intracellular degradation of [125I]IF occurred during normal cellular transcytosis of [57Co]Cbl and in one h following internalization the major intracellular degradation products of IF were two polypeptides of Mr 29 kDa and 19 kDa. The size of the major degradation product of IF in the basolateral media was 10 kDa. Based on these results, we suggest that IF is internalized by the renal epithelial cells and is degraded by leupeptin-sensitive acid proteases during Cbl transcytosis. PMID- 1734859 TI - Avian species-specific tandem repeats contain nuclear protein binding sites. AB - Three avian highly repetitive tandem repeats were identified and examined. These repeats had similar unit lengths (about 42 bp long) but completely different sequences each containing particular protein binding sites. Each of these repeats was found within only one of the five closely related genera studied. PMID- 1734860 TI - PRS3 encoding an essential subunit of yeast proteasomes homologous to mammalian proteasome subunit C5. AB - We found by computer analysis that a putative yeast proteasome subunit gene named PRS3 that encodes a protein very similar to subunit C5 of rat and human proteasomes is located immediately 3' to the ERD2 gene of Saccharomyces cerevisiae. The similarity of the primary structures of the two suggests that this subunit may have a common function in proteasomes of all eukaryotes. The protein, deduced from the open reading frame of PRS3, consists of 242 amino acid residues with a calculated molecular weight of 27,077. Chromosomal disruption of the PRS3 gene created a recessive lethal mutation. Physical mapping by hybridization to intact S. cerevisiae chromosomal DNA showed that the PRS3 gene is located on chromosome II, unlike two other subunit genes, PRS1 and PRS2, which are located on chromosomes XV and VII, respectively. These findings indicate that the PRS3 protein is a subunit of yeast proteasomes that is essential for cell viability. PMID- 1734861 TI - Purification and characterization of a calpain activator from human platelets. AB - A calpain (Ca(2+)-activated neutral protease) activator was purified from human platelets by ammonium sulfate fractionation, gel-filtration, ion-exchange chromatography, followed by heat-treatment. The purified calpain activator with a Mr of 47.5 kDa was a heat-stable protein as demonstrated in other cells. The calpain activator did not change the Ca2+ sensitivity of calpain but activated calpain activity about 2-fold. This calpain activator may play an important role in the activation of the protease system leading to the Ca(2+)-mediated physiological process of platelets. PMID- 1734862 TI - Binding site mapping of a photoaffinity-labeled juvenile hormone binding protein. AB - The juvenile hormone binding protein (JHBP) of larval Manduca sexta was labeled by a photoaffinity analog of JH II and purified by preparative IEF and ion exchange HPLC. The purified [3H]EHDA-labeled JHBP was selectively cleaved by CNBr and by endoproteinases Lys-C and Glu-C. The radioactive peptides were separated by tricine SDS-PAGE and sequenced after blotting to a PVDF membrane. The sequence revealed that Ala184-Asn226 contained a primary binding site of [3H]EHDA. Furthermore, peptide mapping indicated that Asp1-Glu34 also contained a second covalent attachment site of [3H]EHDA. Labeling of the N-terminal region increased when the photolysis was performed at lower temperature. Since Ala184-Asn226 is predicted to be a hydrophobic beta-sheet region, it may participate in the recognition of lipophilic backbone of JH. Five out of six cysteines are located in these two regions, consistent with a model in which the two binding regions connected by disulfide bridges provide a two-sided binding pocket for juvenile hormone. PMID- 1734863 TI - Alkaline phosphatase activity during differentiation of the human promyelocytic leukemia cell line, HL-60. AB - The differentiation of HL-60 promyelocytic cells toward mature myelocytic cells induced by retinoic acid (RA) was accompanied by a quantitative similar increase in alkaline phosphatase (ALP) activity. The potentiation of RA-induced differentiation and the enhancement of ALP activity by sphinganine seemed to correlate with each other. The combination of RA and sphinganine increased in parallel the percentage of mature cells and the ALP activities. Short exposures (4-8h) of HL-60 cells to RA promoted differentiation and ALP activity to a fraction (about 50%) of their maximums which were achieved in cells after 24h or longer RA exposure. Our results indicate that the key step for the induction of ALP activity and the differentiation by RA probably takes place within 24h of incubation. PMID- 1734864 TI - Partial deletion of a dystrophin gene leads to exon skipping and to loss of an intra-exon hairpin structure from the predicted mRNA precursor. AB - In dystrophin Kobe exon 19 of the dystrophin gene is skipped during the process of mRNA precursor splicing even though the splice sites are unchanged (Matsuo et al. J. Clin. Invest. 87:2127-2131,1991). In the predicted secondary structure of the mRNA precursor, exon 19 of dystrophin Kobe is paired with intron sequences, whereas a large part of exon sequence from wild type is paired with itself and folded into a large hairpin structure. As all of 22 additional dystrophin exons analyzed also form intra-exon hairpin structures, these structures may be considered essential components of exons. We suggest that the abolishment of a hairpin structure in the truncated exon of dystrophin Kobe might prevent the splicing machinery from recognizing the splice sites and induce exon skipping. PMID- 1734865 TI - A novel primer extension method to detect the number of CAG repeats in the androgen receptor gene in families with X-linked spinal and bulbar muscular atrophy. AB - X-linked spinal and bulbar muscular atrophy (SBMA), an adult-onset form of motor neuron disease, was recently reported to be caused by amplification of the CAG repeats in the androgen receptor gene. We report here a simple and rapid strategy to detect the precise number of the CAGs. After the DNA fragment containing the CAG repeats is amplified by the polymerase chain reaction, a primer extension is carried out; the extension of the end-labelled reverse primer adjacent to 3' end of CAG repeats stops at the first T after CAG repeats with the incorporation of dideoxy ATP in the reaction mixture. The resultant primer products are analysed by denaturing polyacrylamide gel electrophoresis and autoradiography. This method could be quite useful to detect not only CAG repeats in SBMA but also other polymorphic dinucleotide and trinucleotide repeats. PMID- 1734866 TI - A novel transthyretin mutation associated with familial amyloidotic polyneuropathy. AB - We characterized the mutation associated with familial amyloidotic polyneuropathy in a Japanese patient. Sequence analysis of polymerase chain reaction-amplified exons of the transthyretin gene revealed a novel point mutation resulting in a substitution of arginine for glycine at position 47. The mutation was confirmed using allele-specific olgonucleotide hybridization procedures. This most likely represents a de novo mutation since neither parent carries the mutant allele. PMID- 1734867 TI - Isolation and primary structure of a novel pheromonotropic neuropeptide structurally related to leucopyrokinin from the armyworm larvae, Pseudaletia separata. AB - A novel pheromonotropic neuropeptide has been isolated from a head extract of the armyworm larvae, Pseudaletia separata, by a seven step purification procedure using an in vivo assay with decapitated female moths of Bombyx mori. Amino acid sequence analysis and comparison with synthetic peptides established the primary structure of the peptide, termed Pseudaletia pheromonotropin (Pss PT), as H-Lys Leu-Ser-Tyr-Asp-Asp-Lys-Val-Phe-Glu-Asn-Val-Glu-Phe-Thr-Pro-Arg-Le u-NH2. Pss PT is structurally related to leucopyrokinin, an insect myotropic neuropeptide, and possesses the C-terminal pentapeptide, Phe-Thr-Pro-Arg-Leu-NH2, responsible for the biological activity. PMID- 1734868 TI - P2 protamines from human sperm are zinc -finger proteins with one CYS2/HIS2 motif. AB - P1 (HP1) and P2 (HP2, HP3, HP4) protamines were isolated from human sperm nuclei in the reduced form and their interaction with zinc and cobalt was studied. One zinc atom per molecule of P2 protamines but not of P1 protamine was found. Absorption spectra of P2 protamines with cobalt were characteristic of a tetrahedral complex involving two histidine and two cysteine residues and with one cobalt per molecule. A tetrahedral complex was found neither in P1 protamines nor in P2 protamines alkylated at cysteine or at histidine residues. The zinc finger motif Cys2/His2 of P2 protamines may play a role in stabilization of human sperm chromatin and in inhibition of transcription. PMID- 1734869 TI - Oxidized low density lipoproteins exert arrhythmogenic effects in rabbit Purkinje fibers. AB - The electrophysiological effects of oxidized low density lipoproteins (ox-LDLs) have been studied in rabbit Purkinje fibers using standard microelectrode techniques, in comparison with native LDLs (n-LDLs) and lysophosphatidylcholine (LPC). At the concentration of 100 micrograms protein/ml, ox-LDL but never n-LDL induced the abrupt occurrence of abnormal electrical activities during the basic stimulation of 1 Hz (6/13 fibers) and the development of either early afterdepolarizations (6/13 fibers) or abnormal automaticity (4/13 fibers) at low frequencies (0.1 and 0.03 Hz). Short trains of rapid stimulation (2, 3, 4 and 5 Hz) did not trigger delayed afterdepolarizations. However, early afterhyperpolarizations were commonly seen after each action potential. 30 microM LPC caused quite similar electrophysiological derangements. The results suggest that ox-LDLs may exert arrhythmogenic effects partly explained by their LPC content. PMID- 1734870 TI - Synthesis and characterization of a d(ApG) platinated nonanucleotide duplex. AB - The nonamer 5'd(CTCAGCCTC) 3' 1 has been reacted with cis diamminediaquaplatinum(II) in water at pH 4.2. The major reaction product was shown by enzymatic digestion and 1H NMR to be the d(ApG)cis-Pt(NH3)2 chelate [cis Pt(NH3)2[d(CTCAGCCTC)-N7(4),N7(5)]] 1-Pt. When mixed with its complementary strand 2, 1-Pt forms a B DNA type duplex 3-Pt with a Tm of 35 degrees C (versus 58 degrees C for the unplatinated duplex). The NMR study of the exchangeable protons of 3-Pt revealed that the helix distortion is localized on the CA*G*-CTG moiety (the asterisks indicating the platinum chelation sites) with a strong perturbation of the A*(4)T(15) base pair related to a large tilt of A*(4). PMID- 1734871 TI - The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44. AB - We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms. PMID- 1734872 TI - Differential requirement of ATP and extra-ribosomal proteins for ribosome inactivation by eight RNA N-glycosidases. AB - The requirement of ATP and extra-ribosomal proteins for the inactivation of ribosomes by eight plant RNA N-glycosidases [ribosome-inactivating proteins (RIPs)] was investigated. Tritin, pokeweed antiviral protein and barley RIP depend, as gelonin [Sperti, S., Brigotti, M., Zamboni, M., Carnicelli, D. and Montanaro, L. (1991) Biochem. J., 277, 281-284], on the presence of ATP and extra ribosomal proteins for full inactivation of ribosomes, while bryodin, lychnin, momordin, momorcochin and saporin inactivate isolated Artemia salina ribosomes suspended in buffer saline. PMID- 1734873 TI - Stereochemistry of NADPH oxidation by dihydropyrimidine dehydrogenase from pig liver. AB - Dihydropyrimidine dehydrogenase reduces uracil to 5,6-dihydrouracil in a strictly NADPH-dependent reaction. Either by analysing the 1H-NMR spectra of the NADP+ products formed or by determination of the kinetic isotope effects of stereospecifically deuterated coenzymes dihydropyrimidine dehydrogenase was found to abstract specifically the pro-S hydrogen of NADPH, making it a member of the B side stereospecific class of dehydrogenases. PMID- 1734874 TI - Tissue specificity of S14 and fatty acid synthase in vitro transcription. AB - Hepatic nuclear extracts support in vitro transcription from S14 and fatty acid synthase (FAS) promoters. Renal nuclear extracts support in vitro transcription from S14 promoter constructs at rates comparable to hepatic nuclear extracts, but lack the apparent positive and negative control observed with liver. In contrast, renal nuclear extracts do not support in vitro transcription from the FAS promoter. NF-1 or a related protein in both hepatic and renal extracts contributes to in vitro transcriptional activity from the S14 promoter, but not the FAS promoter. These studies indicate that different mechanisms regulate tissue-specific expression of S14 and FAS. PMID- 1734875 TI - Effect of extracellular phosphatidylinositol on c-myc gene-expressed human renal cancer cell line. AB - Effect of exogenously added soybean phosphatidylinositol on c-myc gene expressed and unexpressed human cancer cell lines was investigated. When phosphatidylinositol liposomes were introduced into culture media, viability of c myc unexpressed cells was reduced, while that of c-myc expressed cells was not. Death of c-myc unexpressed cells by phosphatidylinositol liposomes was found to be caused by abnormally accumulated intracellular Ca2+, and it seemed to be related to reduction of protein kinase C activity. PMID- 1734876 TI - Role of the metF and metJ genes on the vitamin B12 regulation of methionine gene expression: involvement of N5-methyltetrahydrofolic acid. AB - The repression of MetE synthesis in Escherichia coli by vitamin B12 is known to require the MetH holoenzyme (B12-dependent methyltransferase) and the metF gene product. Experiments using trimethoprim, an inhibitor of dihydrofolate reductase, show that the MetF protein is not directly involved in the repression, but that N5-methyltetrahydrofolic acid (N5-methyl-H4-folate), the product of the MetF enzymatic reaction is required. Since the methyl group from N5-methyl-H4-folate is normally transferred to the MetH holoenzyme to form a methyl-B12 enzyme, the present results suggest that a methyl-B12 enzyme is involved in the vitamin B12 repression of metE expression. Other results argue against the possibility that a methyl-B12 enzyme functions in this repression solely by decreasing the cellular level of homocysteine, which is required for MetR activation of metE expression. Experiments with metJ mutants show that the MetJ protein mediates about 50% of the repression of metE expression by B12 but is totally responsible for the regulation of metF expression by vitamin B12. PMID- 1734877 TI - Expression of mouse-GLUT3 and human-GLUT3 glucose transporter proteins in brain. AB - Polyclonal anti-peptide antisera were raised to the C-terminal sequence of mouse- and human-GLUT3 glucose transporter isoforms. GLUT3 protein and mRNA expression were investigated by Western blot and Northern blot assays, in a range of tissues and cell lines. Mouse-GLUT3 protein was detected only in rat brain, where it was present in most regions except adenohypophysis and pineal gland. Mouse-GLUT3 was also detected in primary cultured rat cerebellar neurons and the neuronal cell lines PC12 and NG108-15, but not in cultured astroglia. Human-GLUT3 protein was detected in CHO cells transfected with the human-GLUT3 cDNA and in human brain, but not in human placenta or fat. The expression of GLUT3 in rat brain and neurons indicates it is a major neuronal glucose transporter. PMID- 1734878 TI - Decreased fidelity of DNA polymerases and decreased DNA excision repair in aging mice: effects of caloric restriction. AB - Hepatic DNA polymerases from calorie restricted and ad libitum 26 month old C57BL/6 mice showed a decline in fidelity of nucleotide incorporation compared with weanling animals. Both alpha and beta polymerases from calorie restricted aged mice exhibited a higher level of fidelity than polymerases from ad libitum aged mice. UV-initiated unscheduled DNA synthesis was significantly higher in hepatocytes from weanling and 18 month old calorie restricted animals compared with cells from 18 month old ad libitum animals, while MMS-initiated unscheduled DNA synthesis did not differ significantly between cells from young and old or ad libitum and calorie restricted animals. These data suggest that calorie restriction could play a significant role in decreasing the age-related decline of cellular mechanisms expected to reduce the rate at which mutations accumulate during aging, and could potentially prolong the onset age of mutation-associated diseases of the elderly. PMID- 1734879 TI - The effect of interleukin-4 on the macrophage respiratory burst is species dependent. AB - Preexposure of human monocytes to recombinant human interleukin-4 (IL-4) suppressed the respiratory burst response to a number of different stimuli, including phorbol myristate acetate, zymosan, platelet-activating factor and the chemotactic peptide, f-met-leu-phe. Under similar conditions, the respiratory burst of murine macrophages was enhanced by preexposure to recombinant murine IL 4. By conducting our studies on cells from different species under similar conditions we have demonstrated that there is a significant disparity in the effects of IL-4 on human and murine macrophages thus providing an explanation for some apparent inconsistencies in the literature and highlighting the need for caution when extrapolating data across species barriers. PMID- 1734880 TI - Interleukin-1 impairs both vascular contraction and relaxation in rabbit isolated aorta. AB - Incubation of rabbit aortic rings with interleukin-1 (100 U/ml) in vitro led to a depressed contractile response to norepinephrine, whether the endothelium was present or not. In both cases norepinephrine-induced contraction was restored in the presence of NG-methyl-L-arginine (300 microM), an inhibitor of nitric oxide synthesis. In interleukin-1-treated rings precontracted with norepinephrine (1 microM), the relaxing response to acetylcholine was totally suppressed independently on the presence of endothelium. High concentrations of acetylcholine (greater than 1 microM) induced a slight contraction which was of lower amplitude than that obtained in control endothelium-denuded rings and was increased in the presence of NG-methyl-L-arginine. These results show that interleukin-1 (i) affects not only vascular contraction but also relaxation and (ii) involves both endothelial and non-endothelial factors. These observations suggest an impairment of the whole vascular reactivity during septic shock. PMID- 1734881 TI - Coordinate regulation of oestrogen and prolactin receptor expression by sodium butyrate in human breast cancer cells. AB - Prolactin receptor and oestrogen receptor are co-ordinately expressed in human breast cancer cell lines and in human breast tumour biopsies, leading to the suggestion that the expression of these receptors may be coupled. To examine this hypothesis, T-47D and MCF-7 human breast cancer cells were treated with sodium butyrate, a known modulator of oestrogen receptor levels, and the changes in oestrogen and prolactin receptor mRNA and binding activity were measured. In both cell lines treatment with 0.3-10 mM sodium butyrate resulted in a parallel decrease in prolactin and oestrogen receptor mRNA levels and binding activity. In T-47D cells, where the effect was transient, mRNA levels of both receptors recovered in parallel. These data indicated that oestrogen receptor and prolactin receptor gene expression is modulated in parallel by sodium butyrate and supported the hypothesis that the expression of these two receptors is coupled. PMID- 1734882 TI - Enhanced intracellular activation of carboplatin in hemoglobin-synthesizing versus undifferentiated erythroleukemic cells. AB - The formation of DNA interstrand cross-links following exposure of target cells to the antineoplastic drugs Cisplatin and Carboplatin was measured in murine erythroleukemic cells either native or induced to differentiate and to synthesize hemoglobin by treatment with hexamethylene bisacetamide. The uptake of both drugs was identical in the uninduced and the induced cells, thus excluding differences in permeability due to differentiation. Both cell types formed comparable levels of DNA interstrand cross-links when submitted to treatment with Cisplatin. Conversely, significant differences were observed after exposure to Carboplatin. Specifically, the induced, hemoglobin containing cells showed significantly enhanced intracellular activation of the drug and subsequent binding to DNA, compared to the uninduced cells. These data suggest that, in agreement with previous results obtained with erythrocytes, the hemoglobin present in the committed cells enhances the aquation process that mediates the activation of Carboplatin. PMID- 1734883 TI - Production of monoclonal antibodies against human 6-pyruvoyl tetrahydropterin synthase and immunocytochemical localization of the enzyme. AB - Monoclonal antibodies were produced against human pituitary gland 6-pyruvoyl tetrahydropterin synthase, one of the key enzymes in the biosynthesis of tetrahydrobiopterin, by in vitro immunization with the antigen directly blotted from SDS-PAGE to polyvinylidene difluoride membranes. The antibodies produced show crossreactivity in the enzyme linked immunosorbent assay, not only with the human 6-pyruvoyl tetrahydropterin synthase but some also with the same enzyme isolated from salmon liver. 6-Pyruvoyl tetrahydropterin synthase was localized immuno-enzymatically in peripheral blood smears and in skin fibroblasts by the use of these monoclonal antibodies and the alkaline phosphatase monoclonal anti alkaline phosphatase labeling technique. PMID- 1734884 TI - The role of 5'-methylthioadenosine on rat calvaria cell differentiation. AB - The role of 5'-methylthioadenosine (MTA), formed during the process of polyamine biosynthesis, on differentiation of osteoprogenitor cells was assessed by its effects on alkaline phosphatase (ALP) activity, bone nodule formation and osteopontin contents of cultured rat calvaria (RC) cells. These three markers were stimulated by exogenous MTA and were depressed by 5' difluoromethylthioadenosine (DFMTA), a synthetic inhibitor of MTA phosphorylase, which cleaves MTA to adenine and 5-methylthioribose-1-phosphate. 5 Methylthioribose and 2-keto-4-methylthiobutyrate, metabolites of 5 methylthioribose-1-phosphate, had no effects on ALP activity and bone nodule formation in the presence or absence of DFMTA. On the other hand, adenine enhanced ALP activity, bone nodule formation and osteopontin contents in mineralized nodules and also partially reversed DFMTA-induced inhibition of these three markers. MTA, its metabolites and DFMTA did not affect the growth of RC cells under these culture conditions. These results suggest that adenine formed from MTA is important in the differentiation of RC cells. PMID- 1734885 TI - Translocation and induction of alpha B crystallin by heat shock in rat glioma (GA 1) cells. AB - Response to heat shock of alpha B crystallin expressed in rat astrocytoma GA-1 cells was analysed quantitatively using an immunoassay method. GA-1 cells contained a considerable amount of alpha B crystallin at growing phase. When the growing cells were heated at 45 degrees C, concentrations of alpha B crystallin in cell extracts were decreased to less than one-fifth of the original level within 15 min, with an increase in the insoluble fraction which was detected by immunoblotting. The low level of alpha B crystallin in the cytoplasm, that was observed for a few hours after heat shock, gradually recovered to the control level within several hours. At 10 h following heat shock (45 degrees C for 15 min), the concentration of alpha B crystallin in the soluble extract was about twice that of the control level, with little detectable amounts in the insoluble fraction. These results are additional evidence that suggest that alpha B crystallin is a small heat shock protein. PMID- 1734886 TI - The role of calcium in neutrophil migration: the effect of calcium and calcium antagonists in electroporated neutrophils. AB - Chemotaxis by electroporated rabbit peritoneal neutrophils in the absence of Ca2+ is only slightly different from that in the presence of Ca2+. Pretreatment of neutrophils with quin2-AM causes inhibition of chemotaxis. Calcium antagonists as nitrendipine and verapamil are inhibitory in nanomolar concentrations, while 10(5) times higher concentrations are required for inhibition of chemotaxis by neutrophils which were not electroporated. The results support the hypothesis that Ca2+ from Ca(2+)-storing organelles is of importance for chemotaxis, but that chemotaxis is not dependent on changes in cytoplasmic Ca2+ concentrations. PMID- 1734887 TI - Presence of islet amyloid polypeptide in rat islet B and D cells determines parallelism and dissociation between rat pancreatic islet amyloid polypeptide and insulin content. AB - The islet amyloid polypeptide (IAPP) immunoreactivity of the adult rat pancreas is located in insulin-containing B cells as well as in somatostatin-containing D cells. In both cell types, the IAPP immunoreactivity is identical to rat synthetic IAPP in terms of its elution position after reversed phase HPLC and its binding to IAPP antibodies. The IAPP content per 10(6) B-cells is more than 100 fold lower than the corresponding insulin content, but comparable to the IAPP content of D cells. After induction of diabetes by streptozotocin, pancreatic IAPP seems predominantly located in somatostatin-containing cells. In normal rats, pancreatic insulin and IAPP content increase 20 fold from birth to 12 weeks of age; beyond week 12, the further rise in pancreatic insulin was not paralleled by an increase in IAPP content. PMID- 1734888 TI - Isoflavonoids, genistein, psi-tectorigenin, and orobol, increase cytoplasmic free calcium in isolated rat hepatocytes. AB - Isoflavonoid compounds, genistein, psi-tectorigenin and orobol have been implicated as inhibitors of tyrosine-specific protein kinase and phosphatidylinositol turnover. These compounds have been frequently used as a pharmacological tool to assess signal transduction pathways in various cell systems. In the course of analyzing signaling pathways in rat hepatocytes, we obtained an unexpected finding that these compounds transiently increase cytoplasmic free calcium. Since the Ca2+ mobilizing effect was observed in 1 microM calcium containing buffer, the source of the Ca2+ may be intracellular stores. Thus, when interpreting data obtained using these compounds, caution is needed. PMID- 1734889 TI - Carbon 13 NMR study of glycogen metabolism in the baboon liver in vivo. AB - In vivo glycogen metabolism was investigated at 2 Tesla by 13C NMR in the baboon liver. Two concentric surface coils were used for 13C observation and proton decoupling, respectively. Spectra were acquired in 2 to 10 minutes with a 60 ms repetition time. After 3 hours of glucose infusion in the 48 hr fasted animal, 3 g of 99%-enriched [1-13C]glucose were injected. The distribution of the label on C-1 and also C-2, C-5 and C-6 of glycogen indicated 65% and 35% contributions of the direct and indirect pathways to glycogen synthesis from glucose, respectively. The results show that hepatic metabolic pathways and rates can be followed in vivo in large animals by 13C NMR at 2 Tesla. PMID- 1734890 TI - Both stimulatory and inhibitory GDP/GTP exchange proteins, smg GDS and rho GDI, are active on multiple small GTP-binding proteins. AB - Six peaks of small GTP-binding proteins (G proteins) were separated by column chromatographies from the cytosol fraction of the differentiated HL-60 cells: two peaks of rho p21, one peak of smg/rap1 p21, two peaks of rac1 p21, and one peak of an unidentified small G protein with a Mr of about 20,000 (20 KG). smg GDS, previously thought to be a stimulatory GDP/GTP exchange protein for smg p21, Ki ras p21, and rho p21, but not for Ha-ras p21 or smg p25A, was also active on rac1 p21. rho GDI, previously thought to be an inhibitory GDP/GTP exchange protein specific for rho p21, was also active on rac1 p21. These results indicate that both smg GDS and rho GDI are active on multiple small G proteins. PMID- 1734891 TI - Pyruvate/malate antiporter in rat liver mitochondria. AB - To gain some insight into the process by which both acetylCoA and NADPH, needed for fatty acid synthesis, are obtained, in the cytosol, from the effluxed intramitochondrial citrate, via citrate lyase and malate dehydrogenase plus malic enzyme respectively, the capability of externally added pyruvate to cause efflux of malate from rat liver mitochondria was tested. The occurrence of a pyruvate/malate translocator is here shown: pyruvate/malate exchange shows saturation features (Km and Vmax values, measured at 20 degrees C and at pH 7.20, were found to be about 0.25 mM and 2.7 nmoles/min x mg mitochondrial protein, respectively) and is inhibited by certain impermeable compounds. This carrier, together with the previously reported tricarboxylate and oxodicarboxylate translocators proved to allow for citrate and oxaloacetate efflux due to externally added pyruvate. PMID- 1734892 TI - Calpain activation is essential for membrane fusion of erythrocytes in the presence of exogenous Ca2+. AB - The membrane mobility agent, 2-(methoxyethoxy)ethyl-cis-8-(2 octylcyclopropyl)octanoate (A2C) promotes the fusion of rat, rabbit, and human erythrocytes in the presence of exogenous Ca2+. Under these conditions, the high sensitivity form of calcium-activated neutral protease (mu-calpain) in erythrocytes is activated autolytically. mu-Calpain is activated in accordance with fusion; that is, both erythrocyte fusion and autolytic activation of mu calpain are induced in rat erythrocytes at 30 min, in rabbit erythrocytes at 150 min, and in human erythrocytes at 240 min after the addition of A2C and Ca2+. When erythrocytes are preincubated with the Ca2+ ionophore A23187, both fusion and autolytic activation start earlier. A leupeptin analogue, Cbz-Leu-Leu-Leu aldehyde (ZLLLal), inhibits both the autolytic activation of mu-calpain and fusion induced by A2C and Ca2+. These results indicate that treatment of erythrocytes with A2C and Ca2+, results in first an influx of Ca2+ into the cells, followed by autolytic activation of mu-calpain, proteolysis of membrane proteins, exposure of fusion-sites, and, finally, fusion of erythrocytes. PMID- 1734893 TI - 6-pyruvoyl tetrahydropterin synthase from salmon liver: amino acid sequence analysis by tandem mass spectrometry. AB - The most frequent variant of atypical phenylketonuria, an inborn error of metabolism, is characterized by a low activity of the 6-pyruvoyl tetrahydropterin synthase. We purified and characterized this enzyme from salmon liver known to contain high levels. After digestion, peptides were sequenced by tandem mass spectrometry and/or automated Edman microsequence analysis. Both a free amine terminus and an N-acetylated amine terminus were found, indicating the presence of two isoforms. The peptide sequences determined here have a high degree of homology with the protein sequence deduced from cDNA for rat 6-pyruvoyl tetrahydropterin synthase (1), however, the amine termini of these proteins differ significantly. PMID- 1734894 TI - A 1H-NMR study of the solution conformation of cyclo(GRGDSPA): conformational effects on the physiological activity. AB - Solution conformations of cyclo(GRGDSPA) have been analyzed by the use of two dimensional proton nuclear magnetic resonance spectroscopy and the dynamical simulated annealing calculation. It has been shown that the RGDS segment in cyclo(GRGDSPA) takes a beta-turn conformation. We have concluded that this beta turn conformation is essential for the physiological activity of cyclo(GRGDSPA). PMID- 1734895 TI - Membrane transport in disease and treatment. Proceedings of the Fifth Biochemical Pharmacology Symposium. Oxford, 25-26 July 1991. PMID- 1734896 TI - Potassium channels in nervous tissue. AB - There is a multiplicity of potassium channels in nervous tissue. These have been characterized on the basis of their electrophysiological actions but more information is required on their structures and on the functions of the different subtypes of channel in different parts of the nervous system. We currently also lack drugs which are specific in opening or closing individual subtypes of channel. However, when more is known about the structure and function of these channels and when more specific modulators of their activity are available, it is likely that the use of such compounds may be of great value in the treatment of a variety of conditions affecting the nervous system, including epilepsy, the damage due to cerebral anoxia, neurodegenerative disorders and demyelinating disorders. PMID- 1734897 TI - Effects of isozyme selective phosphodiesterase inhibitors on bovine tracheal smooth muscle tone. PMID- 1734898 TI - Recent progress in potassium channel opener pharmacology. AB - Potassium (K) channel openers comprise a diverse group of molecules capable of opening K channels in excitable cells. These agents exhibit their greatest potency in the smooth muscle system but K channels in cardiac muscle, neurones and in secretory cells are also affected. The development of tissue selectivity is currently one major focus of research and evidence is starting to emerge that this can be achieved. The profound effects of the K channel openers in vivo has led to the suggestion that an endogenous K channel opener might exist and exert an important role in blood pressure homeostasis. The discovery of such a substance--endothelium-derived hyperpolarizing factor--has many implications and its role in cardiovascular regulation is currently under investigation. In vivo, initial studies with the K channel openers emphasized their antihypertensive properties. However, later studies have concentrated on the improvement to coronary blood flow produced by these substances together with their protective effect on the ischaemic myocardium, the basis of which is not fully understood. In spite of great efforts, the K channel which forms the target of these agents in smooth muscle is a matter of controversy. The ability of glibenclamide to antagonize the actions of the K channel openers initially led to the suggestion that an ATP-dependent K channel was their site of action in smooth muscle although the most recent data have implicated a smaller conductance K channel. PMID- 1734899 TI - Quinoline-containing antimalarials--mode of action, drug resistance and its reversal. An update with unresolved puzzles. AB - Malaria constitutes one of the major health threats in the tropical and sub tropical areas of the world. Yet, few advances were made in recent years in revealing the mode of action of the common and most economically affordable antimalarial drugs, the schizontocidal 4-aminoquinolines. Data presented indubitably repudiate the previous notions that these drugs act by either halting the feeding of the parasite on its host erythrocyte cytosol or repressing nucleic acid synthesis due to intercalation into the parasite's DNA. A novel target for drugs is outlined, i.e. they are shown to inhibit in vitro the release of iron from acidified host cell cytosol, consisting mostly of hemoglobin, a process that could provide this trace element to the parasite. Resistance to quinoline containing drugs is the principal reason for the present resurgence of malaria. Drug-resistant parasites accumulate less of these weak base-like drugs in the acidic digestive vacuoles. A kinetic model is presented, indicating that diminishing drug accumulation is due to decreased vacuolar proton pump activity and is not a result of a putative multidrug resistance (MDR) efflux pump. Findings to date on the molecular biology of parasite mdr genes are reviewed. These indicate no correlation between gene expression or mutations and phenotypic drug resistance. Reversal of parasite drug resistance by relevant compounds in MDR cancer cells seems to involve mechanism(s) different from the inhibition of the MDR pump in cancer cells. PMID- 1734900 TI - Single or multiple localization of ADP/ATP transporter in human malarial Plasmodium falciparum. PMID- 1734901 TI - Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis. 84-month update. AB - OBJECTIVE: To determine the long-term efficacy and safety of low-dose methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Eighty-four-month open prospective trial at a single academic rheumatology center. RESULTS: Twenty-six patients were enrolled in a prospective study of the long-term efficacy of MTX in RA; a significant improvement had been demonstrated after 36 months of therapy. Twelve patients remained in the study at the 84-month visit; the mean weekly dosage of MTX was 10.2 mg. A significant improvement was still noted at 84 months in the number of painful joints, number of swollen joints, joint pain index, joint swelling index, and physician and patient global assessments. A 50% improvement in the joint pain index and joint swelling index was observed in more than 80% of the 12 patients still enrolled. A significant reduction in prednisone dosage was achieved; of 14 patients taking prednisone at entry, 7 had discontinued prednisone completely. Fourteen patients withdrew from the study: 10 between 0 and 36 months, and 4 between 36 and 84 months. Toxicity in 3 patients and visit noncompliance in 1 patient were the reasons for withdrawal between 36 and 84 months. At 84 months, 46% of the patients remained in the study; 11.5% had discontinued due to MTX toxicity. CONCLUSION: The effectiveness of MTX in the treatment of RA continues to be demonstrated in this prospective study, after 84 months of treatment. PMID- 1734902 TI - Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Update after a mean of 90 months. AB - OBJECTIVE: To determine and describe the clinical, radiographic, and toxicity profile in a cohort of rheumatoid arthritis patients receiving weekly oral methotrexate (MTX) over a mean period of 90 months, and to compare and contrast these data with our previous data on this cohort, reported after 53 months. METHODS: Prospective, open observational study over a mean treatment period of 90 months (range 79-107 months). Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, 1 month, 3 months, and every 3 months thereafter. RESULTS: A significant improvement from baseline was maintained in all clinical parameters but the number of tender joints. Toxic reactions were as common in months 54-90 as during the first 53 months. The mean dosage of MTX decreased from 14.6 mg/week at the time of the last report to 11.7 mg/week, while the mean prednisone dosage increased from 1.9 mg/day to 2.1 mg/day. Radiographic scores for erosive disease became statistically significantly different from baseline at year 8, and scores for joint space narrowing differed significantly from baseline at years 5 and 8. Since study entry, 2 patients (6.9%) have experienced MTX pneumonitis. CONCLUSION: We conclude that a majority of rheumatoid arthritis patients are able to continue MTX treatment with generally sustained efficacy, for intervals that meaningfully exceed those reported previously. PMID- 1734903 TI - The effect of local heat and cold therapy on the intraarticular and skin surface temperature of the knee. AB - OBJECTIVE: To evaluate the effects of local application of ice chips, ligno paraffin, short-wave diathermy, and nitrogen-cold air on skin and intraarticular temperature. METHODS: Forty-two healthy subjects were divided into 4 treatment groups. A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours, by treatment group, were recorded. RESULTS: The mean skin surface temperature dropped from 27.9 degrees C to 11.5 degrees C after application of ice chips, and from 28.8 degrees C to 13.8 degrees C after application of cold air. The mean intraarticular temperature decreased from 31.9 degrees C to 22.5 degrees C and from 32.9 degrees C to 28.8 degrees C, respectively, after these 2 treatments. Shortwave diathermy increased skin temperature by 2.4 degrees C; intraarticular temperature was increased only 1.4 degrees C by short-wave diathermy. Treatment with ligno-paraffin increased the skin surface temperature 8.9 degrees C; the temperature in the joint cavity was increased 3.5 degrees C. CONCLUSION: The use of short-wave diathermy and superficial heat packs in the treatment of patients with arthritis may potentially cause harm by increasing intraarticular temperature. This may have major implications regarding treatment policy for patients with arthritis. PMID- 1734904 TI - Timing of pregnancy in relation to the onset of rheumatoid arthritis. AB - The interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age-matched normal women (controls) who had been assigned a "dummy date for RA onset" for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04-2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8-17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8-7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation. PMID- 1734905 TI - The rapid assessment of disease activity in rheumatology (radar) questionnaire. Validity and sensitivity to change of a patient self-report measure of joint count and clinical status. AB - OBJECTIVE: This study documents the measurement properties of a brief, self administered questionnaire of disease signs and symptoms in patients with rheumatoid arthritis. METHODS: The Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire assesses joint pain/tenderness and clinical status. One hundred ninety-three pairs of RADAR forms were completed by 45 subjects and their assigned clinician evaluators. RESULTS: Subject-clinician agreement (intraclass correlation coefficients [ICC]) for joint pain/tenderness and clinical status ranged from 0.52 to 0.87 (P = 0.0001), with 83% greater than or equal to 0.65. The ICC for change in joint scores over 6 months was 0.83 (P = 0.0001). CONCLUSION: The 2-page RADAR questionnaire produces valid estimates of joint count and clinical status that are sensitive to change. PMID- 1734906 TI - Regulation of B cell function by lobenzarit, a novel disease-modifying antirheumatic drug. AB - OBJECTIVE: Lobenzarit (disodium 4-chloro-2,2'-iminodibenzoate [CCA]) is a novel disease-modifying drug for the treatment of rheumatoid arthritis (RA). Although its clinical efficacy has been demonstrated, its mechanism of action remains unclear. We therefore examined the effects of CCA on in vitro IgM and IgM rheumatoid factor (IgM-RF) production by human B cells. METHODS: IgM and IgM-RF production was induced from highly purified B cells from 8 healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus factors generated from mitogen-activated T cells (TCF) or with immobilized anti-CD3-activated CD4+ T cells. RESULTS: CCA suppressed the production of IgM-RF as well as IgM at concentrations of 25-50 micrograms/ml (therapeutic serum concentrations of the drug), although the IgM-RF production induced by SAC plus TCF was suppressed at lower concentrations of CCA (1-3 micrograms/ml). Whereas CCA suppressed interleukin-2 (IL-2) production by anti-CD3-activated CD4+ T cells, its suppressive effects on B cells were not overcome by addition of IL-2 or TCF. CCA did not inhibit the initial stages of B cell activation in either culture system, but rather, suppressed the maturation of previously activated B cells. Cell cycle analysis by acridine orange staining indicated that CCA-mediated inhibition of B cell responsiveness induced by anti-CD3-activated CD4+ T cells was the result of a block at the G1-S interphase. CONCLUSION: These results indicate that CCA suppresses the production of IgM and IgM-RF by directly inhibiting activated B cells. Thus, one of the actions of CCA in RA may be the suppression of the function of activated B cells. PMID- 1734907 TI - Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. AB - OBJECTIVE: To determine whether anti-Ro/SS-A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization. METHODS: An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed. RESULTS: Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti-La/SS-B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti-native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produced alterations in membrane repolarization. CONCLUSION: Anti-Ro/SS-A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus. PMID- 1734908 TI - Antibiotic treatment of venereal disease and Reiter's syndrome in a Greenland population. AB - OBJECTIVE: To assess the effects of antibiotic treatment of urethritis or cervicitis on the incidence of recurrences of articular symptoms in Reiter's syndrome patients. METHODS: Retrospective evaluation of the medical charts of 109 patients living in Greenland. RESULTS: Thirty-seven percent of the episodes of genitourinary tract inflammation that were not treated or were treated with penicillin were followed by arthritis, compared with 10% of those treated with tetracycline or erythromycin. CONCLUSION: Antibiotics active against Chlamydia trachomatis reduced the risk of postvenereal arthritis in the population studied. PMID- 1734909 TI - P-31 magnetic resonance spectroscopy in polymyositis and dermatomyositis. Altered energy utilization during exercise. AB - OBJECTIVE: To explore alterations in energy utilization as a potential etiology for weakness in polymyositis and dermatomyositis (PM/DM). METHODS: P-31 magnetic resonance spectroscopy studies were performed in patients with acute and treated PM/DM and in normal controls, at rest and with exercise. RESULTS: Patients with acute and treated PM/DM showed increased ratios of inorganic phosphate to phosphocreatine (PCr) during exercise, with loss of ATP disproportional to loss of PCr. CONCLUSION: This study demonstrates changes in energy utilization in PM/DM, thus supporting the notion of a metabolic etiology for the weakness associated with these diseases. PMID- 1734910 TI - Racial differences in the frequencies of scleroderma-related autoantibodies. AB - OBJECTIVE: To determine demographic differences in scleroderma-related autoantibodies. METHODS: One hundred fifty-six patients with systemic sclerosis were prospectively examined for anticentromere antibodies (ACA), anti topoisomerase I (anti-topo I, or Scl-70), antinucleolar, and anti-U1 RNP autoantibodies. RESULTS: ACA was found in 36% of Caucasians and 4% of American blacks (P = 0.002, odds ratio [OR] 15). Anti-topo I was found in 37% of American blacks, compared with 17% of Caucasians (P = 0.04, OR 3). No significant differences in the frequencies of antinucleolar and anti-U1 RNP autoantibodies were found. CONCLUSION: These data suggest important demographic differences in scleroderma-associated autoantibodies. PMID- 1734911 TI - Serologic evaluation of patients receiving procainamide. AB - This controlled study examined the characteristics of serologic abnormalities in 52 patients receiving procainamide for cardiac arrhythmias, who had no symptoms of a connective tissue disease. Antinuclear antibodies occurred in 43 patients (83%). Significant elevation of antibody binding to single-stranded DNA (mean +/- SEM 30 +/- 2.6%), double-stranded DNA (13 +/- 1.1%), Z-DNA (optical density 0.54 +/- 0.06), and poly A (7.2 +/- 0.6%) was seen (P less than 0.001). Thirty-four patients (65.4%) had antibodies to total histones, most frequently, the H2A/2B dimer. IgG antibodies to H2A/2B correlated with the cumulative procainamide dose. One patient subsequently developed drug-related lupus. PMID- 1734912 TI - Articular cartilage vesicles generate calcium pyrophosphate dihydrate-like crystals in vitro. AB - OBJECTIVE: To identify the morphology of a mineral-forming of adult porcine hyaline articular cartilage digest and characterize the mineral it forms. METHODS: Electron microscopy, Fourier transform infrared (FTIR) spectroscopy, x ray microanalysis, compensated polarized light microscopy, and biochemical studies including 14C-labeled UDPG pyrophosphohydrolase radiometric assay. RESULTS: This fraction of articular cartilage digest contained membrane-limited vesicles resembling growth plate cartilage matrix vesicles and formed mineral after only 24 hours in physiologic salt solution containing 1 mM ATP: The mineral contained inorganic pyrophosphate, 95% of which derived from ATP, and phosphate, 93% of which derived from inorganic phosphate in the medium. The FTIR spectrum of this mineral closely resembled the spectrum of standard calcium pyrophosphate dihydrate (CPPD) crystals. Compensated polarized light microscopy showed positively birefringent, rod-shaped crystals morphologically identical to CPPD. Ca:P ratios, defined by energy-dispersive microanalysis, were also consistent with CPPD. CONCLUSION: The articular cartilage vesicle fraction of porcine hyaline cartilage is capable of generating mineral that strongly resembles CPPD. PMID- 1734913 TI - Bone marrow changes in adjuvant-induced and collagen-induced arthritis. Interleukin-1 and interleukin-6 activity and abnormal myelopoiesis. AB - OBJECTIVE: To investigate the role of bone marrow in arthritis. METHODS: Bone marrow changes over time were investigated in rats with adjuvant-induced and collagen-induced arthritis, using bioassay techniques and histologic analysis. RESULTS: In both animal models, bone marrow interleukin-1 and interleukin-6 activity began to rise before the onset of arthritis and increased in relation to the progression of arthritis. Enhanced myelopoiesis in the bone marrow was noted in conjunction with the increased cytokine activity. CONCLUSION: Bone marrow changes such as those demonstrated in this study may be common to various models of induced arthritis and may have an important role in the pathogenesis of this disease. PMID- 1734914 TI - Failure of multitarget detection of Borrelia burgdorferi-associated DNA sequences in synovial fluids of patients with juvenile rheumatoid arthritis: a cautionary note. PMID- 1734915 TI - Volatiles from interactions of Maillard reactions and lipids. AB - This article provides current information on the production of volatile compounds from interactions of Maillard reactions and lipids. It includes a brief introduction outlining the Maillard reactions, the Strecker degradation of amino acids, and the oxidation of lipids. It highlights those compounds derived from these reactions that could interact to form volatile flavor components during the processing or cooking of food. The article discusses results obtained from model systems involving interactions between (1) Maillard reaction products and carbonyl compounds, (2) amino acids and carbonyl compounds, (3) amino acids and derivatives of fatty acids, and (4) Maillard reaction products, triglycerides and phospholipids. The qualitative and quantitative effects that triglycerides and phospholipids have on the formation of volatile Maillard products are also discussed. Particular attention is given to those long-chain alkyl heterocyclic compounds formed during these reactions, proposed methods for their formation, and their aromas. The role that such compounds play in food flavors is discussed with reference to those volatile compounds identified in certain cooked foods, such as meat (beef, lamb, and pork), chicken, potatoes (baked, French-fried, and crisps), and beverages (coffee, tea, and cocoa). PMID- 1734916 TI - Carotenoids and retinoids in human nutrition. AB - Since the discovery of vitamin A as a fat-soluble growth factor in the early part of the century, research into carotenoids and retinoids has attracted the attention of many scientists. These two groups of compounds are still being actively studied all over the world since many gaps in knowledge exist and new frontiers are being pursued. Recent developments in studies into the possible roles of carotenoids and retinoids beyond their classical functions in vision have created a great deal of excitement in the biomedical community. This review covers a wide range of topics pertaining to these two closely related compounds. Particular emphasis is given to the functions of these compounds and their roles in human nutrition. Various aspects of vitamin A deficiency and studies on carotenoids and retinoids in cancer development and prevention are reviewed in some detail. PMID- 1734917 TI - A review of sweet taste potentiation brought about by divalent oxygen and sulfur incorporation. AB - The plethora of high-potency sweetener research has allowed the construction of important structure-taste relationships. In light of new structure-taste relationships, it is instructive to review sweet taste potentiation brought about by divalent oxygen and sulfur incorporation. The taste of sulfur-containing organic compounds was reviewed in Japanese by Yasuo Ariyoshi in 1977. Several new representative examples of sweet taste potentiation and taste dichotomy (sweet and bitter) found within similar classes of oxygen- and sulfur-containing organic compound: amides, dipeptides, ureas, sulfamates, sulfonamides, oximes, sugars, dihydroisocoumarins, and others are reviewed. Special attention is given to the thioethers and thioureas in sulfamates, dipeptides, aryl ureas, and hybrid dipeptide ureas. The most notable contributions have arisen from the work of Nofre and Tinti at Universite Claude Bernard in Lyons, France. A common trend emerges with certain sweeteners when a carbon atom is strategically replaced by sulfur or oxygen atoms. The net result is an increase in the sweetness two- to tenfold. With saccharins, the usual bitter, metallic taste is removed. Sweet taste receptor models that have been published are mainly based on the original Shallenberger and Acree model of the glucophores AH-B with contributions from Kier (AH-B-X). AH is a proton donor group, B is a proton acceptor group, and X is some hydrophobic group. All of the models have overlooked the contributions of divalent sulfur (often in place of oxygen) in bringing about sweetness potentiation. There is no precedence for localizing the energy-minimized structures of sulfur-containing sweeteners in a binding mode that includes sulfur. These sulfur potentiation loci are analyzed and illustrated in a computer generated sweetener model to show the specific region in which sulfur is being "recognized" as a potentiating feature. PMID- 1734918 TI - Dual asymmetric PCR: one-step construction of synthetic genes. AB - We have developed a one-step process for constructing synthetic genes. Four adjacent oligonucleotides 17-100 bases in length having short overlaps of 15-17 bases are used as primers in a PCR mixture. The quantity of the two internal primers is highly limited, and the resultant reaction causes an asymmetric single stranded amplification of the two halves of the total sequence due to an excess of the two flanking primers. In subsequent PCR cycles, these dual asymmetrically amplified fragments, which overlap each other, yield a double-stranded, full length product. PMID- 1734919 TI - An efficient method for blunt-end ligation of PCR products. AB - This report presents data demonstrating a simple method that can potentially be extended to a wide range of cloning strategies to increase the yield of insert containing recombinants. The method requires that the ligation of an insert to a vector does not regenerate the original restriction enzyme recognition sequence. In the example presented, PCR products were blunt-end ligated to a SmaI-cut vector, in the presence of SmaI endonuclease. The addition of the restriction enzyme to the ligation reaction dramatically favored the ligation of insert to vector rather than vector self-ligation. PMID- 1734920 TI - A rapid PCR method of screening for small mutations. AB - We report a modified method of screening for point mutations using a PCR approach based upon the sensitivity of PCR to the 3' terminus of the primer. This method provides a sensitive screen when using either plasmid DNA or bacterial cell lysates. We have optimized the technique for general use to allow rapid screening of mutants with good discrimination. Unlike previous similar methods, this technique has no inherent limitation in primer design on the 3'-terminal base chosen. PMID- 1734921 TI - Using PCR to extend the limit of oligonucleotide synthesis. AB - A method has been developed to allow one to extend the practical limit of oligonucleotide synthesis by coupling the synthesis reaction to a subsequent PCR. Given that DNA synthesizers are capable of producing reasonable yields of oligonucleotides that are 125-150 bases in length, this method could be used to recover the minute amount of full-length product present in mixtures extended well beyond the established limits. This technology could be applied to gene synthesis and mutagenesis. PMID- 1734922 TI - Dideoxy linear PCR on a commercial fluorescent automated DNA sequencer. AB - The use of automated fluorescent DNA sequencer systems and PCR-based DNA sequencing methods play an important role in the actual effort to improve the efficiency of large-scale DNA analysis. Here we show the application of the linear PCR using a single fluorescent primer and dideoxynucleotide terminators in four separate sequencing reactions on the EMBL/Pharmacia's fluorescent automated DNA sequencer. We have used dideoxy/deoxynucleoside triphosphate ratios and linear amplification cycle conditions to obtain an accurate sequencing response of up to, and over, 500 bases from just 400 ng of double-stranded DNA template without chemical denaturation. The sequencing protocol described in this paper is effectively suited for enhancement of sensitivity and performance of the automated DNA sequencing system. PMID- 1734923 TI - Recovery of plasmid DNA from nonviable bacterial colonies and cultures. PMID- 1734924 TI - Reverse fluorescent sequencing of large M13 clones. PMID- 1734925 TI - Nearly complete loss of nucleic acids by commercially available highly purified ethanol. PMID- 1734926 TI - EGTA inhibition of DNase activity in commercial lysostaphin preparations. PMID- 1734927 TI - Rapid removal of cesium chloride from DNA obtained from ultracentrifuge gradients. PMID- 1734928 TI - A simple and rapid procedure for pouring sequencing gels. PMID- 1734929 TI - PCR amplification of specific alleles (PASA) is a general method for rapidly detecting known single-base changes. AB - Previous data suggested that PCR amplification of specific alleles (also known as allele-specific amplification and amplification refractory mutation system) is not a general method for rapidly and accurately detecting known single-base changes. Herein we present our experience with the use of PCR amplification of specific alleles to detect 69 polymorphic or mutant alleles. Our results indicate that with proper optimization, all alleles were reliably distinguished. PMID- 1734930 TI - Gene conversion of immunoglobulin variable regions in mutagenesis cassettes by replacement PCR mutagenesis. AB - A technique, Replacement PCR Mutagenesis, was developed to replace one immunoglobulin variable region (V) in a M13 phage cassette with a different, homologous V. This allows the use of the same mutagenesis and subsequent expression vectors for many V regions or V segments. The method combines PCR of V fragments and in vitro mutagenesis. Primers homologous to 3' and 5' ends of both V regions initiate PCR synthesis of the V DNA fragment (donor) that will replace the V region (recipient) in M13. Donor V PCR DNA may originate from mRNA, cloned V genes or genomic templates. The donor V PCR DNA is denatured and annealed to the M13 cassette containing the recipient V to be supplanted. The second strand is synthesized, transfected into bacteria and mutant plaques selected by hybridization. Since restriction sites in primers are not required, altered primer-encoded amino acids are avoided. Further, the PCR donor piece can be of any length if it shares homology with the recipient gene. This allows construction and expression of complete gene replacements and chimeras. This method is also applicable to V "humanization" and studying sets of homologous genes containing polymorphic or evolutionary disparities. The potential uses of the technique are discussed. PMID- 1734931 TI - PCR amplification and simultaneous digoxigenin incorporation of long DNA probes for fluorescence in situ hybridization. AB - Nonradioactive in situ hybridization has found widespread applications in cytogenetics. Basic requirements are DNA probes in sufficient amounts and of high specificity as well as a labeling protocol of good reproducibility. The PCR has been of fundamental importance for the amplification of DNA sequences and thus for the production of DNA probes. Meanwhile, PCR protocols for amplification of DNA have reached a high degree of automation. So far, incorporation of labeled nucleotides into these DNA probes has normally been done by nick translation. Here we show that in using the PCR, amplification of a DNA probe larger than one kilobase accompanied by simultaneous incorporation of digoxigenin-11-dUTP can be performed for in situ hybridization experiments. As an example, the DNA probe pUC 1.77 specific for the subcentromeric region q12 of chromosome number 1 was used and hybridized against metaphase chromosomes from human lymphocytes. The labeled chromosome region was detected by anti-digoxigenin-fluorescein, Fab fragments. The experiments were evaluated by digital image analysis of microphotographs. PMID- 1734932 TI - The effect of oxidation/reduction on the charge heterogeneity of the human glucocorticoid receptor. AB - In order to investigate the molecular basis for the charge heterogeneity which has been reported for the glucocorticoid receptor, we have analyzed the [3H]dexamethasone mesylate ([3H]DM)1 affinity labeled receptor from HeLa S3 cells by high resolution two-dimensional gel analysis. The [3H]DM labeled glucocorticoid receptor from HeLa cells exists as a population of 5-6 isoforms which range over approx. 0.6 pI units but have similar molecular weights. This heterogeneity is apparently the result of modification(s) of a single gene product since the affinity labeled receptor from Chinese hamster ovary (CHO) cells transfected with the human glucocorticoid receptor cDNA displays the same pattern of heterogeneity on two-dimensional gels. Since previous one-dimensional gel studies from our laboratory showed that the structure of the [3H]DM labeled glucocorticoid receptor from HeLa cells is highly susceptible to sulfhydryl group modification, we investigated the potential role of the same modifications in the apparent charge heterogeneity of the glucocorticoid receptor. Treatment of the affinity labeled receptor with iodoacetamide which alkylates free sulfhydryl groups and irreversibly prevents the formation of intra- or intermolecular disulfide bonds, reproducibly resulted in the appearance of 5-6 discrete isoforms of the receptor protein. Treatment with dithiothreitol, a reversible reducing reagent, resulted in detection of 3 to 4 isoforms of the glucocorticoid receptor. In marked contrast, treatment with sodium tetrathionate, which induces intramolecular disulfide bond formation, resulted in only one detectable isoform of the [3H]DM labeled glucocorticoid receptor. These data demonstrate that the oxidation/reduction state of sulfhydryl groups within the receptor protein can account for much of the charge heterogeneity of this ligand dependent transcription factor. PMID- 1734933 TI - Tissue localization of 11 beta-hydroxysteroid dehydrogenase and its relationship to the glucocorticoid receptor. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) dictates specificity for the mineralocorticoid receptor (MR) by converting the active steroid cortisol to cortisone in man (corticosterone to 11-dehydrocorticosterone in rodents), leaving aldosterone to occupy the MR. However cortisol is the principal circulating glucocorticoid in man and 11 beta-HSD, distributed in a tissue specific fashion, may represent a powerful mechanism in regulating exposure of active steroid to the glucocorticoid receptor (GR). A detailed localization study of 11 beta-HSD gene expression and activity in numerous rat tissues has been performed and compared with the presence of GR mRNA. 11 beta-HSD mRNA (1.4 kB) measured by hybridization to a cDNA derived from hepatic 11 beta-HSD, and enzyme activity, measured by percentage conversion of [3H]corticosterone to [3H]11 dehydrocorticosterone by tissue homogenate, was widespread, present in all tissues studied except spleen, brain cortex and heart. There was a close correlation between tissue 11 beta-HSD mRNA levels and activity (r = 0.91, P less than 0.001) suggesting pretranslational regulation of the enzyme at a tissue level. There was also close co-localization of GR mRNA (7 kB), measured by hybridization to a rat GR cRNA probe, and enzyme mRNA/activity in every tissue studied except heart and brain cortex in which GR mRNA was found. In the mineralocorticoid target tissues kidney and colon, additional 11 beta-HSD mRNA bands were seen (kidney 1.8 kB, colon 3.4 kB), suggesting the presence of multiple dehydrogenase species. 11 beta-HSD is widely distributed and suitably placed to modulate ligand occupancy of the GR. The possibility of multiple dehydrogenase species in mineralocorticoid target tissues is consistent with the hypothesis that the ubiquitous 'native' 1.4 kB hepatic enzyme regulates the GR, and these separate dehydrogenases regulate the MR. PMID- 1734934 TI - Kinetic mechanism of reduction of testosterone by hepatic 5 beta-reductase of chicken and inhibition of the reductase activity by a secosteroid, an azasteroid and glycyrrhetinic acid. AB - The present studies on initial velocity of testosterone reduction by hepatic 5 beta-reductase (4-en-3-oxosteroid 5 beta-reductase) of chicken and mode of inhibition of the 5 beta-reduction by 5 beta-dihydrotestosterone and NADP+ indicated that the reduction of testosterone occurred after the 5 beta-reductase bound firstly to NADPH and then to testosterone, forming a ternary complex. After 5 beta-reduction, 5 beta-dihydrotestosterone and then NADP+ were liberated from the complex, following a mechanism of "ordered Bi-Bi". Effect of (4R)-5,10-seco 19-norpregna-4,5-diene-3,10,20-trione (a steroidal 5 alpha-reductase-inhibitor or Secosteroid), diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (the other steroidal 5 alpha-reductase-inhibitor or 4-MA), and glycyrrhetinic acid (3 beta-hydroxy-11-oxoolean-12-en-30-oic acid, a 5 beta-reductase-inhibitor) was examined upon the 5 beta-reductase activity by double reciprocal plots. The mode of inhibition against testosterone by 4-MA and glycyrrhetinic acid was found to be competitive, while that by Secosteroid was non-competitive. PMID- 1734935 TI - Isoelectric focusing and 2D electrophoresis of the human androgen receptor. AB - Nuclear androgen receptors from cultured genital skin fibroblasts were analyzed by non-denaturing isoelectric focusing (IEF) in ultrathin polyacrylamide gels before and after photoaffinity labeling with [3H]methyltrienolone. Both reversibly and covalently labeled receptors focused at pH 5.28 +/- 0.20 when extracted from nuclei with high salt. Lowering of the salt concentration yielded, in both cases, a second species which focused at pH 7.16. This species became predominant when nuclei were sonicated in IEF sample buffer containing no salt, even after extensive nucleic acid digestion. Low salt cytosols from both prostate and foreskin focused as a single peak of pI: 4.93 +/- 0.31 which remained unchanged when KCl was added to the cytosol up to a concentration of 0.6 M. SDS polyacrylamide gel electrophoresis of photoaffinity labeled receptors revealed labeled proteins with Mw 90-95 kDa. Two-dimensional electrophoresis of photoaffinity labeled nuclear receptors, extracted in low or high salt, showed that the two isoforms (pI 5.28 and 7.16) contain the same steroid-binding subunit with Mw 90-95 kDa. Nuclear receptors from 4 patients with the receptor positive form of the Complete Androgen Insensitivity Syndrome (CAIS, Rc+) were analyzed by non-denaturing IEF: a single species was observed, focusing at pH 6.0 whether in high or low salt conditions. These results indicate that the nuclear androgen receptor is an acidic protein with pI 5.28 and Mw 90-95 kDa under maximum protein dissociation conditions. When extracted under low salt conditions, it can be isolated in a neutral form (pI 7.16) suggesting its association with a nuclear protein. Receptors of (CAIS, Rc+) patients have an abnormal charge and show no pI shift upon lowering of the salt concentration suggesting that this shift could be a significant step in the mechanism of action of androgens. PMID- 1734936 TI - Intrinsic estrogenicity of some progestagenic drugs. AB - The intrinsic estrogenic activity of some progestins cannot be properly evaluated by using hormone responsive systems when the chosen end-points are also sensitive to progestagenic activity, usually antagonistic of estrogenic actions. We have therefore applied to the evaluation of some drugs commonly used in contraceptive and hormone replacement formulations a recently developed in vitro method to estimate estrogenic activities, which is based on measurements of the estrogen stimulated alkaline phosphatase activity in cells of the Ishikawa-Var I human endometrial adenocarcinoma line, a response not influenced by progestins. Whereas progesterone, medroxyprogesterone acetate and danazol were found to be devoid of estrogenic activity in this assay, Org OD-14, norethynodrel, gestrinone (R 2323), norethindrone and dl-norgestrel provoked half maximal increases in alkaline phosphatase activity at concentrations (EC-50) of 7, 14, 140, 200 and 2900 nM, respectively, under conditions in which the corresponding value for estradiol was 8 pM. This intrinsic estrogenic activity can be inhibited by antiestrogens, as verified by reversing the effect of R 2323 with 4-hydroxytamoxifen. Since prostaglandin F2 alpha output by secretory endometrium is increased by estrogens and diminished by progestins, this end-point can serve to evaluate the net effect of drugs with intrinsic estrogenic and progestagenic activities. For instance, R 2323 showed estrogenic activity in this assay whereas Org OD-14 did not. The same in vitro system can be used to evaluate estrogen antagonistic activities of test compounds, using estradiol as the agonist. These in vitro systems are useful in establishing a profile of activities of a drug on a relevant human target tissue, in the screening of synthetic or natural compounds under investigation, and in studies on structure/action relationships. PMID- 1734937 TI - Pituitary progestin-metabolizing enzyme activities in the aged female rat. AB - Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha hydroxysteroid oxidoreductase (3 alpha-HSOR) enzymic activities (NADH-linked and NADPH-linked) were measured in anterior pituitaries (AP) from aged female rats during three stages of reproductive senescence (constant estrus: CE; repeated pseudopregnancies: PSP; and anestrus: AN). To assess ovarian influence on these enzymes during these stages of reproductive aging, we also determined enzyme levels from ovariectomized rats from each stage treated with estrogen or vehicle. Progesterone 5 alpha-reductase and NADH-linked 3 alpha-HSOR activities were 2 fold higher in pituitaries of CE rats as compared to those of PSP and AN rats. NADPH-linked 3 alpha-HSOR levels did not differ among the three stages. All three enzyme levels were elevated 2- to 5-fold as compared to the corresponding enzyme levels from young cycling rats. After ovariectomy (10 days), 5 alpha-reductase activity in PSP and AN rats was elevated 3- to 4-fold relative to mean levels in intact PSP and AN rats. Ovariectomy had no effect on 5 alpha-reductase levels in CE rats. Under similar conditions, young cycling rats exhibit a 10-12-fold increase. Treatment of ovariectomized PSP and AN rats for 3 days with estradiol benzoate (10 micrograms/day) restored 5 alpha-reductase levels. Ovariectomy had no effect on the NADPH-linked 3 alpha-HSOR levels in CE, PSP or AN animals which is similar to that observed with young rats. Ovariectomy also had no effect on the NADH-linked 3 alpha-HSOR levels except for the CE group. The ovariectomized CE rats exhibited reduced pituitary NADH-linked 3 alpha-HSOR levels (30%). In contrast, young rats exhibit elevated pituitary NADH-linked 3 alpha-HSOR levels after ovariectomy (4- to 5-fold). These changes suggest the possibility that altered processing of progesterone and its 5 alpha- and 3 alpha-reduced products may be one means by which the effectiveness of progesterone is reduced during aging. The results also suggest an altered ovarian role in the regulation of these enzymes. PMID- 1734938 TI - Aromatase inhibition by 7-substituted steroids in human choriocarcinoma cell culture. AB - Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase both in vitro and in vivo. Several of these agents have exhibited higher affinity for the enzyme complex than the substrate. In order to examine further the interaction(s) of 7-substituted steroids with aromatase, 7 substituted 4,6-androstadiene-3,17-diones were synthesized and demonstrated competitive inhibition of aromatase activity in human placental microsomes. 7 Substituted 1,4,6-androstatriene-3,17-diones demonstrated mechanism-based inhibition of placental aromatase activity. These agents were evaluated for inhibition of aromatase activity in the JAr human choriocarcinoma line. The 7 substituted 4,6-androstadiene-3,17-diones produced dose dependent inhibition of aromatase activity in the cell cultures, with IC50 values ranging from 490 nM to 4.5 microM. However, these agents are less effective when compared to other steroidal inhibitors, such as 7 alpha-thiosubstituted androstenediones. These results on the 7-substituted 4,6-androstadiene-3,17-diones are consistent with the data from biochemical enzyme inhibition studies using human placental aromatase. On the other hand, 7-phenethyl-1,4,6-androstatriene-3,17-dione exhibits greater inhibitory activity, with an IC50 value of 80 nM. Other mechanism-based inhibitors, 7 alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17 dione and 4-hydroxyandrostenedione, also exhibited potent inhibition of aromatase activity in JAr cells. In summary, the most effective B-ring modified steroidal aromatase inhibitors are those derivatives that can project the 7-aryl substituent into the 7 alpha-position. PMID- 1734939 TI - A conspicuous down-regulating effect of morphine on essential steroid hydroxylation reactions and certain drug N-demethylations. AB - This study was conducted to explore the potency of morphine to induce reductions of specific cytochrome P450 isoenzyme functions. Male Sprague-Dawley rats were treated with escalating doses (20-125 mg/kg per day) of morphine for 2 weeks in order to study the effects on the following cytochrome P450 catalyzed reactions: 16 alpha-hydroxylation of dehydroepienderosterone (DHA) and progesterone; 17 alpha- and 21-hydroxylation of progesterone; N-demethylation of ethymorphine, codeine and morphine as well as O-dealkylation of ethylmorphine and codeine. 16 alpha-Hydroxylation of DHA and progesterone and 17 alpha-hydroxylation of progesterone decreased to 18, 12 and 10% of control activities, respectively. The N-demethylation of ethylmorphine and codeine decreased to 34 and 43% of control activities, respectively. Morphine treatment had no effect on the 21 hydroxylation reactions or the O-dealkylation of ethylmorphine or codeine. A monoclonal antibody (Mab) against rat liver cytochrome P450 2 c/RLM 5 exerted a 66-73% inhibition of the N-demethylation of ethylmorphine and codeine, respectively, whereas the O-dealkylation reactions were not affected. This Mab inhibited the 16 alpha- and 17 alpha-hydroxylation of DHA and progesterone, whereas the 21-hydroxylation reactions were unaffected. The steroid hydroxylation reactions in rat adrenals were not altered upon morphine treatment. Our data suggest that a major part of the 16 alpha- and 17 alpha-steroid hydroxylations are catalyzed by the same (or closely related) cytochrome(s) P450 as the opioid N demethylation reactions. PMID- 1734940 TI - Phospholipases modulate immature pig testicular androgen and 16-androstene biosynthetic pathways in vitro. AB - The role of membrane phospholipids in porcine testicular androgen and 16 androstene biosynthesis was examined by monitoring the effects of phospholipase treatments on the activities of the steroid transforming enzymes. Untreated (control) microsomes from immature pig testes converted pregnenolone to 17 hydroxypregnenolone and DHA to 5,16-androstadien-3 beta-ol (andien-beta) and 4,16 androstadien-3-one (dienone) in the 16-androstene pathway, these metabolites accounting for most (65%) of the pregnenolone converted. The 4-ene steroids in the androgen pathway (progesterone, 17-hydroxyprogesterone, androstenedione and testosterone) totalled less than 10% of the pregnenolone metabolites. No estrogens or 5 alpha-reduced metabolites were detected. Treatment with phospholipase A2 or C, decreased the conversion of pregnenolone to 4-ene-3-oxo steroids but did not decrease the quantities of 5-ene-3 beta-hydroxysteroids. Confirmation of these findings was obtained by measuring the individual enzymatic steps. Phospholipases A2 and C significantly reduced the conversion of DHA to androstenedione and andien-beta to dienone but did not affect 17-hydroxylase or 'andien-beta-synthetase'. However, when the C-17, 20 lyase step was measured alone, phospholipase C decreased the quantity of androstenedione produced indicating that the side-chain cleavage reaction may involve a lipid component. The different effects of phospholipases on these enzymes suggests that pregnenolone metabolism may be regulated by alterations in the membrane microenvironment. PMID- 1734941 TI - Automation in cervical cytology: an overview. AB - Cancer of the uterine cervix is one of the more common female cancers and a major source of premature female mortality. UK deaths in 1987 exceeded 2000. To reduce these rates, national screening programmes have been introduced using the Papanicolaou method. In screening for cancer, the examination of specimens is an intensive and expensive task. Its high cost has led to a number of attempts to automate the process, either fully or partially. Over the last 30 years, various experimental prescreening systems have been developed for the diagnosis of cytological samples including the use of image processing techniques. This paper presents a historical overview of automation in cervical cytology and the status of current developments for automated cytological diagnosis. PMID- 1734942 TI - An image analysis and statistical evaluation program for the assessment of tumour cell invasion in vitro. AB - Tumour cell invasion is a complex process, which is essential for the formation of metastasis and is therefore of critical clinical importance. For detailed investigations of the invasive process, quantifiable in vitro models of invasion are necessary. In this study we describe an image analysis procedure and a statistical program which facilitate an objective analysis of experiments carried out using the embryonic chick heart invasion model of Mareel. Tumour multicellular spheroids are confronted with embryonic chick heart fragments in culture and are sampled after different time intervals for up to 7 days. Immunohistological sections are then evaluated by an image analysis procedure which provides 9 parameters indicating invasion, proliferation and destruction taking place in the confrontation cultures. The data obtained by image analysis are further evaluated by a statistical program which describes the change with time of each parameter by means of linear regression analysis. Thus the data obtained at various time intervals serve as the source data for a single statistic, namely the slope of the regression line. Confidence intervals and statistical differences between various experiments can be calculated. In order to make the procedure more comprehensible in biological terms, the program provides a full text interpretation of the experimental results. The image analysis procedure in conjunction with statistical evaluation and text interpretation provides a comprehensive tool for the quantitative assessment of experimental invasion in vitro. PMID- 1734943 TI - Characterization of a human renal cell carcinoma specific cytotoxic CD8+ T cell line. AB - Human renal cell carcinoma (RCC) is one of the tumors most sensitive to immunotherapy and in that regard it is similar to malignant melanoma. Clinical studies reporting responses to therapy suggested that a host immune response may be involved in the antitumor activity induced by immunotherapy in these tumors. Although detection of a specific T cell response to melanoma has been well documented, this has not been the case for RCC. The lytic response of interleukin 2 (IL-2) cultured tumor-infiltrating lymphocytes (TILs) from RCC has been nonspecific. However, in this report we describe a CD8+ TIL line derived from a primary RCC tumor that displays specificity for the autologous tumor. This line is lytic for autologous RCC but does not lyse autologous lymphoblasts, allogeneic RCC, or tumor cell lines of other histologic types. It also proliferates specifically to the autologous tumor in the absence of exogenous IL-2. However, the addition of low dose IL-2 to the cultures can significantly augment its proliferative response. When stimulated with autologous RCC but not allogeneic RCC the CD8+ line will produce interferon-gamma (IFN-gamma). It appears that recognition of RCC by this TIL line is through the TCR/CD3 complex because anti CD3 antibody blocks the lytic activity, proliferation and IFN-gamma production of the line in response to the autologous tumor. Additional studies illustrate that cytotoxic T lymphocytes with apparent specificity for the autologous tumor are present in unseparated cultured TILs that can be detected by clonal analysis. Collectively these results suggest that there is a specific T cell response to human RCC. PMID- 1734944 TI - Combined antitumor therapy with the chemotherapeutic drug doxorubicin and an anti transferrin receptor immunotoxin: in vitro and in vivo studies. AB - We have determined the in vitro and in vivo efficacy of the combination of doxorubicin and an anti-transferrin receptor-monoclonal antibody (MAb)-ricin A chain immunotoxin. These agents both possess antineoplastic activity and their differing mechanisms of action and toxicities suggest that they may work well in combination. In vitro cytotoxicity was assayed by the inhibition of both 3H leucine and 3H-thymidine incorporation into H-MESO-1 human malignant mesothelioma cells. In vivo, tumoricidal activity was determined by the effect of treatment on the survival of nude mice bearing H-MESO-1 as an intraperitoneal xenograft. The effect of doxorubicin on the antitumor activity of immunotoxin was directly compared to that of monensin, a well-described immunotoxin potentiator. The coincubation of doxorubicin (1 microM) with immunotoxin in vitro produced no increase in cytotoxicity or rate of cell kill when compared to immunotoxin alone. The addition of monensin to immunotoxin produced a significant increase in both cytotoxicity and the rate of cell kill. In animal trials, all treated groups demonstrated a significant increase in median survival when compared to controls. Treatment with doxorubicin or immunotoxin produced a mean survival time (MST) of 22 and 23 days, respectively, vs. control MST of 10 days. The combination of immunotoxin and doxorubicin increased the MST to 31 days (p = 0.004 vs immunotoxin or doxorubicin alone). Immunotoxin combined with monensin emulsion produced an increase in survival equivalent to doxorubicin/immunotoxin. The use of all three agents produced an additional improvement in survival. Combinations of standard chemotherapeutic drugs and ricin A chain immunotoxins may have additive antitumor effects in the therapy of solid tumors. PMID- 1734945 TI - The persistence of human peripheral lymphocytes, tumor infiltrating lymphocytes, and colon adenocarcinomas in immunodeficient mice. AB - The reconstitution of severely immunodeficient mice with human peripheral blood mononuclear cells (PBMCs) may represent a unique model system to evaluate human antitumor responses. To evaluate this possibility, we studied human PBMC reconstitution, human tumor infiltrating lymphocyte (TIL) persistence, and human colon adenocarcinoma propagation in beige/nude/xid (BNX) and in severe combined immunodeficient (SCID) mice. To evaluate human PBMC reconstitution, 75 mice received 1 x 10(7)-1 x 10(9) human PBMCs i.p. or i.v. and were studied at intervals ranging from 1 to 8 weeks by fluorescence-activated cell sorting (FACS) analysis and by measurement of circulating human immunoglobulin levels. By FACS analyses, only one of 75 mice had evidence of human PBMC persistence at 2 weeks in the spleen. Moreover, liver and peritoneum showed evidence of human cells in only 13 of 56 and 16 of 55 mice, respectively. In these mice, human cells comprised 1-77% of total cells recovered. Human immunoglobulin levels in mouse serum ranged from 0 to 34,000 micrograms/ml and correlated only weakly with evidence of human PBMC reconstitution in peripheral organs, but were generally higher in SCID mice than in BNX mice. Human TIL persistence was evaluated in BNX and SCID mice that were given 3 x 10(7) TILs i.v. (in divided doses) or 1 x 10(8) i.p. TILs along with interleukin-2 administration. At 1, 2, 7, and 14 days following TIL delivery, evidence of human TIL persistence in liver, lung, peritoneum, and spleen was evaluated by FACS analysis. Fresh organ suspensions did not contain human TILs. In mice given cyclophosphamide followed by human TILs i.p., the TILs were demonstrated at 7 days in the SCID peritoneum (leu 4 = 4%) and at 2 days in the SCID spleen (leu 4 = 2%). In BNX mice, 12 of 14 fresh human colon adenocarcinomas were propagated successfully at subcutaneous sites with latency periods ranging from 1 to 13 weeks. Enzymatic disaggregation of tumors greater than 1 cm following one passage yielded 6.5-47 x 10(6) cells with viabilities ranging from 13 to 85%. We conclude that limitations and variability exist in the use of BNX and SCID mice for human PBMC reconstitution, TIL persistence, and propagation of human colon adenocarcinomas. PMID- 1734946 TI - Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells. AB - The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems. Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells. E2-stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM-treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis. All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells. In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells. These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer. PMID- 1734947 TI - Cytokine and natural killing regulation of growth of a hairy cell leukemia-like cell line: the role of interferon-alpha and interleukin-2. AB - Hairy cell leukemia (HCL) is a lymphoproliferative disorder of B-lymphocytes, with pathological manifestations usually including splenomegaly and pancytopenia. Naturally occurring and recombinant interferons (IFNs), specifically of the alpha subtype, have shown a significant anti-tumor effect in HCL patients, with improvement of hematologic parameters within the first few months of treatment. The mechanisms responsible for the beneficial action of IFN-alpha in HCL patients are unclear, but several hypotheses have been suggested. Recently, a continuous line of cells (Eskol) from a patient diagnosed with hairy cell leukemia was established and shown to have several properties of a leukemic hairy cell. In the present study, we investigated the direct effect of IFN-alpha and interleukin (IL 2) on the Eskol cell line, and lymphokine regulation of natural killing (NK) activity against these cells. It was found that IFN-alpha has a direct antiproliferative effect on Eskol cells. Furthermore, Eskol cells were found to be completely resistant to NK-cell mediated cytotoxicity (CMC) but were somewhat sensitive to either IFN-alpha-primed NK or lymphokine-activated killer (LAK) cells-CMC. The resistance of Eskol cells to NK-CMC is due to a low binding ability to effector cells. Moreover, it was found that like IFN, IL-2 can protect Eskol cells from activated NK-CMC. Both cytokines reduced the ability of Eskol cells to induce NK-cytotoxic factor (NKCF) release from NK cells following conjugate formation between Eskol cells and effector cells. Moreover, cycloheximide treatment abolished the protective effect against NK-CMC induced by IFN-alpha or by IL-2. Therefore, it seems that the protective effect against NK CMC induced by both cytokines is mediated via the same mechanism. PMID- 1734948 TI - Phase I trial of interleukin-2 plus gamma-interferon. AB - Interleukin-2 (IL-2) and gamma interferon (gamma-IFN) may be synergistic in inducing cell-mediated antitumor cytotoxicity. In order to determine the dose limiting toxicities and define a maximum tolerated dose of these two agents in combination, we performed a Phase I clinical trial of intravenous IL-2 plus intramuscular gamma-IFN. Patients received both agents on a thrice-weekly schedule consisting of 4 weeks of treatment followed by 2 weeks of rest. Twenty five patients were treated and received gamma-IFN doses between 0.05-0.25 mg/m2 (1-4 x 10(6) U/m2) with IL-2 doses from 0.33 mg/m2 to 2.33 mg/m2 (6-42 x 10(6) IU/m2). Two patients had partial responses of melanoma and adenocarcinoma of the lung lasting greater than 11 and 8 months, respectively. The toxicities of the combination were those expected from each agent, with no unusual effects, no irreversible organ toxicities, and no patient deaths. The doses recommended for outpatient administration on this schedule are IL-2, 2.0 mg/m2 plus gamma-IFN, 0.25 mg/m2, a dose combination that is unassociated with significant organ toxicity. PMID- 1734949 TI - Human antibody response to the intravenous and intraperitoneal administration of the F(ab')2 fragment of the OC125 murine monoclonal antibody. AB - We have characterized the human immune response against murine monoclonal antibodies (HAMA) in 18 patients following administration of the F(ab')2 fragment of the murine monoclonal antibody OC125. OC125 is directed against the CA125 antigen, present on the surface of many human ovarian cancers. An affinity matrix was used to separate serum into immunoglobulin-containing and immunoglobulin-free fractions. HAMA titer was determined on the immunoglobulin fraction with an OC125 sandwich enzyme-linked immunosorbent assay (ELISA). All patients developed an HAMA response, despite the use of F(ab')2 fragments and small amounts (1-4 mg) of antibody. It may be that the intraperitoneal (i.p.) route provides a more marked HAMA response. Enzyme-linked sandwich immunoassays were also used to determine anti-isotype and anti-idiotype titers. Anti-isotype titers were analyzed with antigen irrelevant, isotype-matched murine antibodies and OC125-HRPO. Anti idiotypes titers were assessed in a sandwich assay that utilized F(ab')2 and F(ab') fragments of OC125. The anti-isotype response tended to be of low titer and short duration, while the anti-idiotype response was of high titer and remarkably persistent. HAMA interfered in an unpredictable manner with the correct measurement of serum levels of CA125 in an enzyme immunoassay using OC125. Corrected values of CA125 could be obtained by measurement of antigen in the immunoglobulin-free fraction of serum. The response of one patient, who developed a markedly elevated anti-idiotype titer after serial i.v./i.p. injections, was further characterized and found to contain an antibody consistent with an anti-anti-idiotype to the CA125 antigen. PMID- 1734950 TI - A phase II study of recombinant tumor necrosis factor in renal cell carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. AB - The National Cancer Institute (NCI) Canada Clinical Trials Group conducted a phase II study of recombinant tumor necrosis factor (rTNF) given intravenously daily for 5 days every other week, in measurable metastatic renal cell carcinoma. Two of 26 patients responded with responses lasting greater than 200 days. Toxicity was severe including rigors, fever, headache, fatigue, hypotension, and localized pain. We conclude that rTNF, given as described, has only modest antitumor activity in renal cell carcinoma and produces considerable toxicity. We plan no further studies of rTNF in this disease. PMID- 1734951 TI - Hypoprothrombinemia associated with interleukin-2 therapy: correction with vitamin K. AB - We noted that patients treated with high-dose interleukin (IL)-2 (600,000 IU/kg every 8 h by intravenous bolus) at our institution frequently developed prolongation of their prothrombin time (PT). We therefore performed a prospective study of coagulation function during IL-2 treatment. Since IL-2 treated individuals are known to develop cholestatic liver dysfunction, we hypothesized that the hypoprothrombinemia was due to deficiency of liver-synthesized clotting factors and could be prevented by vitamin K replacement. Alternating patients served as controls or received prophylactic subcutaneous subcutaneous vitamin K. While the nine control patients did not exhibit a significant increase (mean +/- SD) in PT (13.6 +/- 0.6 s pretreatment, 15.0 +/- 2.2 on day 4, and 15.0 +/- 2.5 on day 7, p = 0.77 by repeated measures analysis), three patients developed marked increases in PT (greater than 18 s). Changes in partial thromboplastin time (PTT) over this interval were also not statistically significant. Factor VII levels decreased in all patients from 106 +/- 22 to 59 +/- 16 and 52 +/- 26% on days 4 and 7 (p = 0.0002). Factor VII levels in four patients dropped below the lower limit of normal. Prophylactic treatment of seven patients with vitamin K on days 1-8 of the IL-2 therapy protocol resulted in diminished changes in PT and factor VII compared to control patients (p = 0.02 and 0.003 respectively). No vitamin K-treated patient developed PT or Factor VII levels significantly outside the normal range. Prophylactic vitamin K can prevent hypoprothrombinemia in patients treated with IL-2. This may be of importance in patients with decreased hepatic vitamin K stores, who may be at risk for bleeding complications. PMID- 1734952 TI - Three-dimensional solution structure of Ca(2+)-loaded porcine calbindin D9k determined by nuclear magnetic resonance spectroscopy. AB - The three-dimensional solution structure of native, intact porcine calbindin D9k has been determined by distance geometry and restrained molecular dynamics calculations using distance and dihedral angle constraints obtained from 1H NMR spectroscopy. The protein has a well-defined global fold consisting of four helices oriented in a pairwise antiparallel manner such that two pairs of helix loop-helix motifs (EF-hands) are joined by a linker segment. The two EF-hands are further coupled through a short beta-type interaction between the two Ca(2+) binding loops. Overall, the structure is very similar to that of the highly homologous native, minor A form of bovine calbindin D9k determined by X-ray crystallography [Szebenyi, D. M. E., & Moffat, K. (1986) J. Biol. Chem. 261, 8761 8776]. A model structure built from the bovine calbindin D9k crystal structure shows several deviations larger than 2 A from the experimental distance constraints for the porcine protein. These structural differences are efficiently removed by subjecting the model structure to the experimental distance and dihedral angle constraints in a restrained molecular dynamics protocol, thereby generating a model that is very similar to the refined distance geometry derived structures. The N-terminal residues of the intact protein that are absent in the minor A form appear to be highly flexible and do not influence the structure of other regions of the protein. This result is important because it validates the conclusions drawn from the wide range of studies that have been carried out on minor A forms rather than the intact calbindin D9k. PMID- 1734953 TI - Sequential 1H NMR assignments of kistrin, a potent platelet aggregation inhibitor and glycoprotein IIb-IIIa antagonist. AB - Sequence-specific nuclear magnetic resonances assignments have been obtained for the protons of kistrin. Kistrin is a small naturally occurring snake venom protein that inhibits platelet aggregation by blocking the interaction of fibrinogen with the membrane-bound glycoprotein IIb-IIIa (GP IIb-IIIa), a receptor from the integrin family. Kistrin has an Arg-Gly-Asp sequence which is believed to form an adhesion recognition sequence that is essential for activity. Therefore, the interaction between kistrin and GP IIb-IIIa may provide important information on the motif used by integrins to recognize their target proteins which bear RGD sequences. Kistrin consists of 68 residues and contains six intramolecular disulfide bonds. Although one-third of the amide protons are protected from exchange with the solvent, there appears to be little or no regular secondary structure. The large number of NOE's between residues separated by two and three positions in the sequence indicates that the protein contains a large number of tightly packed loops. Along with the sequential assignments, this paper also discusses the construction and use of computerized data bases for manipulating NMR results. A strategy for computer-assisted sequential resonance using these data bases is also presented. PMID- 1734954 TI - Site-specific binding constants for actinomycin D on DNA determined from footprinting studies. AB - We report site-specific binding constants for the intercalating anticancer drug actinomycin D (Act-D), binding to a 139-base-pair restriction fragment from pBR 322 DNA. The binding constants are derived from analysis of footprinting experiments, in which the radiolabeled 139-mer is cleaved using DNase I, the cleavage products undergo gel electrophoresis, and, from the gel autoradiogram, spot intensities, proportional to amounts of cleaved fragments, are measured. A bound drug prevents DNase I from cleaving at approximately 7 bonds, leading to decreased amounts of corresponding fragments. With the radiolabel on the 3' end of the noncoding strand (A-label), we measured relative amounts of 54 cleavage products at 25 Act-D concentrations. For cleavage of the 139-mer with the label on the 3' end of the coding strand (G-label), relative amounts of 43 cleavage products at 11 Act-D concentrations were measured. These measurements give information about approximately 120 base pairs of the restriction fragment (approximately 12 turns of the DNA helix); in this region, 14 strong and weak Act D binding sites were identified. The model used to interpret the footprinting plots is derived in detail. Binding constants for 14 sites on the fragment are obtained simultaneously. It is important to take into account the effect of drug binding at its various sites on the local concentration of probe elsewhere. It is also necessary to include in the model weak as well as strong Act-D sites on the carrier DNA which is present, since the carrier DNA controls the free-drug concentration. As expected, the strongest sites are those with the sequence (all sequences are 5'----3') GC, with TGCT having the highest binding constant, 6.4 x 10(6) M-1. Sites having the sequence GC preceded by G are weak binding sites, having binding constants approximately 1 order of magnitude lower than those of the strong sites. Also, the non-GC-containing sequences CCG and CCC bind Act-D with a binding constant comparable to those of the weak GGC sites. The analysis may reveal drug-induced structural changes on the DNA, which are discussed in terms of the mechanism of Act-D binding. PMID- 1734955 TI - Structural changes and enhancements in DNase I footprinting experiments. AB - In footprinting experiments, an increase in DNA cleavage with addition of ligand to a system may be due to a ligand-induced structural change. Ligand binding also enhances cleavage by displacing the cleavage agent from ligand-binding sites, thus increasing its concentration elsewhere. The theory and characteristics of this mass-action enhancement are given, and it is shown how it may be recognized. Results of DNase I footprinting of small oligomers, with actinomycin D as ligand, are analyzed to reveal which enhancements are due to mass action, and which can reasonably be ascribed to structural changes. Patterns in the footprinting plots from our experiments on actinomycin D binding to a 139-base-pair DNA fragment (with DNase I as a probe) are studied in the same way. The likely origins of these patterns are discussed, as are enhancements occurring with other probes commonly used in footprinting experiments. PMID- 1734956 TI - Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus. AB - We have previously shown that the synthetic peptide apoE(129-169) forms lipid peptide complexes with dimyristoylphosphatidylcholine (DMPC) with an L:P molar ratio of 125:1; the peptide in the isolated complex contains approximately 56% alpha-helicity. These results verify the presence of an amphipathic alpha-helix in this region of apoE as predicted by Chou-Fasman analysis and hydrophobicity calculations. To further define the lipid binding regions of apoE, we have synthesized four peptides, apoE(211-243), -(202-243), -(267-286), and -(263-286), from the carboxyl terminus of apoE and studied their lipid binding properties; apoE(202-243) contains two potential amphipathic helices. Although all four peptides formed alpha-helices in the helix-forming solvent 30% hexafluoropropanol, we found that only apoE(263-286) formed a stable complex with DMPC. The peptide contained approximately 80% alpha-helicity, and its Trp fluorescence spectrum was blue-shifted by 20 nm in the complex which had an L:P ratio of 163:1. We conclude that this sequence is a newly identified lipid binding region of apoE and that the amphipathic helices 203-221 and 226-243 are too hydrophilic to bind phospholipid. PMID- 1734957 TI - Kinetics of the lamellar-inverse hexagonal phase transition determined by time resolved X-ray diffraction. AB - The kinetics of the lamellar (L alpha)-inverse hexagonal (HII) phase transition in diacylphosphatidylethanolamine (PE)--water systems were probed with time resolved X-ray diffraction. Transition kinetics in the fast time regime (approximately 100 ms) were studied by initiating large temperature jumps (up to 30 degrees C) with a 50-ms electrical current pulse passed through a lipid-salt water dispersion, resulting in ohmic heating of the sample. Diffraction with a time resolution to 10 ms was acquired at the National Synchrotron Light Source. The time constant for the phase transition for 1,2-dioleoyl-sn-glycero-3 phosphoethanolamine (DOPE) was on the order of 100 ms for the largest temperature jumps recorded. Faster transition behavior was found for a 1,2-dielaidoyl-sn glycero-3-PE mixture. The HII lattice parameters for both systems were seen to swell from an initial value commensurate with the lamellar lattice to the final equilibrium value. The rate of swelling was seen to be independent of the magnitude of the temperature jump. For small temperature jumps (less than 10 degrees C), the phase transition kinetics slow dramatically, and transition studies can readily be performed on a conventional rotating anode X-ray source. At 4 degrees C, a DOPE sample was observed to slowly convert to the hexagonal phase over the course of a week, with the decay in the lamellar intensity fitting a power law behavior over four decades of time. This power law behavior is shown to have interesting consequences to the determination of the phase transition temperature of lipid-water dispersions by conventional methods such as calorimetry. PMID- 1734958 TI - Investigation of anion binding to neutral lipid membranes using 2H NMR. AB - The binding of aqueous anions (ClO4-, SCN-, I-, and NO3-) to lipid bilayer membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was investigated using deuterium (2H) and phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy. The ability of these anions to influence the 2H NMR quadrupole splittings of POPC, specifically labeled at the alpha or beta position of the choline head group, increased in the order NO3- much less than I- less than SCN- less than ClO4-. In the presence of these chaotropic anions, the quadrupole splitting increased for alpha-deuterated POPC and decreased for beta deuterated POPC, indicating a progressive accumulation of negative charge at the membrane surface. Calibration of the 2H NMR quadrupole splittings with the amount of membrane-bound anion permitted binding isotherms to be generated for perchlorate, thiocyanate, and iodide, up to concentrations of 100 mM. The binding isotherms were analyzed by considering electrostatic contributions, according to the Gouy-Chapman theory, as well as chemical equilibrium contributions. For neutral POPC membranes, we obtained ion association constants of 32, 80, and 115 M-1 for iodide, thiocyanate, and perchlorate, respectively. These values increase in the order expected for a Hofmeister series of anions. We conclude that the factor determining whether a particular anion will bind to lipid bilayers is the ease with which that anion loses its hydration shell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734959 TI - Deuteron nuclear magnetic resonance study of the dynamic organization of phospholipid/cholesterol bilayer membranes: molecular properties and viscoelastic behavior. AB - The influence of cholesterol on the dynamic organization of 1,2-dimyristoyl-sn glycero-3-phosphocholine (DMPC) bilayers was studied by deuteron nuclear magnetic resonance (2H NMR) using unoriented and macroscopically aligned samples. Analysis of the various temperature- and orientation-dependent experiments were performed using a comprehensive NMR model based on the stochastic Liouville equation. Computer simulations of the relaxation data obtained from phospholipids deuterated at the 6-, 13- and 14-position of the sn-2 chain and cholesterol labeled at the 3 alpha-position of the rigid steroid ring system allowed the unambiguous assignment of the various motional modes and types of molecular order present in the system. Above the phospholipid gel-to-liquid-crystalline phase transition, TM, 40 mol % cholesterol was found to significantly increase the orientational and conformational order of the phospholipid with substantially increased trans populations even at the terminal sn-2 acyl chain segments. Lowering the temperature continuously increases both inter- and intramolecular ordering, yet indicates less ordered chains than found for the pure phospholipid in its paracrystalline gel phase. Trans-gauche isomerization rates on all phospholipid alkyl chain segments are slowed down by incorporated cholesterol to values characteristic of gel-state lipid. However, intermolecular dynamics remain fast on the NMR time scale up to 30 K below TM, with rotational correlation times tau R parallel for DMPC ranging from 10 to 100 ns and an activation energy of ER = 35 kJ/mol. Below 273 K a continuous noncooperative condensation of both phospholipid and cholesterol is observed in the mixed membranes, and at about 253 K only a motionally restricted component is left, exhibiting slow fluctuations with correlation times of tau R perpendicular greater than 1 microsecond. In the high-temperature region (T greater than TM), order director fluctuations are found to constitute the dominant transverse relaxation process. Analysis of these collective lipid motions provides the viscoelastic parameters of the membranes. The results (T = 318 K) show that cholesterol significantly reduces the density of the cooperative motions by increasing the average elastic constant of the membrane from K = 1 x 10(-11) N for the pure phospholipid bilayers to K = 3.5 x 10(-11) N for the mixed system. PMID- 1734960 TI - Importance of phosphatidylethanolamine for association of protein kinase C and other cytoplasmic proteins with membranes. AB - Biological membranes exhibit an asymmetric distribution of phospholipids. Phosphatidylserine (PS) is an acidic phospholipid that is found almost entirely on the interior of the cell where it is important for interaction with many cellular components. A less well understood phenomenon is the asymmetry of the neutral phospholipids, where phosphatidylcholine (PC) is located primarily on exterior membranes while phosphatidylethanolamine (PE) is located primarily on interior membranes. The effect of these neutral phospholipids on protein phospholipid associations was examined using four cytoplasmic proteins that bind to membranes in a calcium-dependent manner. With membranes containing PS at a charge density characteristic of cytosolic membranes, protein kinase C and three other proteins with molecular masses of 64, 32, and 22 kDa all showed great selectively for membranes containing PE rather than PC as the neutral phospholipid; the calcium requirements for membrane-protein association of the 64 and 32-kDa proteins were about 10-fold lower with membranes containing PE; binding of the 22-kDa protein to membranes required the presence of PE and could not even be detected with membranes containing PC. Variation of the PS/PE ratio showed that membranes containing about 20% PS/60% PE provided optimum conditions for binding and were as effective as membranes composed of 100% PS. Thus, PE, as a phospholipid matrix, eliminated the need for membranes with high charge density and/or reduced the calcium concentrations needed for protein-membrane association. A surprising result was that PKC and the 64- and 32-kDa proteins were capable of binding to neutral membranes composed entirely of PE/PC or PC only. The different phospholipid headgroups altered only the calcium required for membrane-protein association. For example, calcium concentrations at the midpoint for association of the 64-kDa protein with membranes containing PS, PE/PC, or PC occurred at 6, 100, and 20,000 microM, respectively. Thus, biological probes detected major differences in the surface properties of membranes containing PE versus PC, despite the fact that both of these neutral phospholipids are often thought to provide "inert" matrices for the acidic phospholipids. The selectivity for membranes containing PE could be a general phenomenon that is applicable to many cytoplasmic proteins. The present study suggested that the strategic location of PE on the interior of the membranes may be necessary to allow some membrane-protein associations to occur at physiological levels of calcium and PS. PMID- 1734961 TI - Isolation and characterization of a stable activation intermediate of the lysosomal aspartyl protease cathepsin D. AB - Procathepsin D is the intracellular aspartyl protease precursor of cathepsin D, a major lysosomal enzyme. Procathepsin D is rapidly processed inside the cell, and, thus, examination of its proteolyic activation and structure has been difficult. To study this proenzyme, a nonglycosylated form of the human fibroblast procathepsin D was expressed in Escherichia coli, refold in vitro, and purified by affinity chromatography on pepstatinyl agarose. Sequence analysis of the refolded, autoactivated enzyme allowed determination of the autoproteolytic cleavage site. The sequence surrounding this cleavage site between residues LeuP26 and IleP27 (in the "pro" region) resembled the first cleavage site found during activation of other aspartyl proteases. Thus, the autoactivated procathepsin D is analogous to the pepsin activation intermediate, which has been termed pseudopepsin. The enzymatic activity, thermal and pH stability, and fluorescence spectra of pseudocathepsin D were compared to mature, predominantly two-chain, cathepsin D isolated from human placenta. The results indicated that pseudocathepsin D and mature enzyme have a similar Km toward a peptide substrate and cleave a protein substrate at identical sites. Temperature stability of the recombinant enzyme was similar to that of the tissue-derived enzyme. However, the recombinant enzyme had increased stability at low pH when compared to the glycosylated tissue-derived two-chain cathepsin D. Fluorescence spectra of the recombinant and tissue-derived enzymes were identical. Thus, the absence of asparagine-linked oligosaccharides and the presence of the remaining segment of propeptide did not significantly alter the structural and enzymatic properties of the enzyme. PMID- 1734962 TI - Identification of two cysteine residues forming a pair of vicinal thiols in glucosamine-6-phosphate deaminase from Escherichia coli and a study of their functional role by site-directed mutagenesis. AB - The nucleotide sequence of the nagB gene in Escherichia coli, encoding glucosamine-6-phosphate deaminase, located four cysteinyl residues at positions 118, 219, 228, and 239. Chemical modification studies performed with the purified enzyme had shown that the sulfhydryl groups of two of these residues form a vicinal pair in the enzyme and are easily modified by thiol reagents. The allosteric transition to the more active conformer (R), produced by the binding of homotropic (D-glucosamine 6-phosphate or 2-deoxy-2-amino-D-glucitol 6 phosphate) or heterotropic (N-acetyl-D-glucosamine 6-phosphate) ligands, completely protected these thiols against chemical modification. Selective cyanylation of the vicinal thiols with 2-nitro-5-(thiocyanato)benzoate, followed by alkaline hydrolysis to produce chain cleavage at the modified cysteines, gave a pattern of polypeptides which allowed us to identify Cys118 and Cys239 as the residues forming the thiol pair. Subsequently, three mutated forms of the gene were constructed by oligonucleotide-directed mutagenesis, in which one or both of the cysteine codons were changed to serine. The mutant proteins were overexpressed and purified, and their kinetics were studied. The dithiol formed by Cys118 and Cys239 was necessary for maximum catalytic activity. The single replacements and the double mutation affected catalytic efficiency in a similar way, which was also identical to the effect of the chemical block of the thiol pair. However, only one of these cysteinyl residues, Cys239, had a significant role in the allosteric transition, and its substitution for serine reduced the allosteric interaction energy, due to a lower value of KT. PMID- 1734963 TI - X-ray absorption fine structure study of the active site of zinc and cobalt carboxypeptidase A in their solution and crystalline forms. AB - A comparative study on the metal environment of Zn(II)-carboxypeptidase A (ZnCPD) and Co(II)-carboxypeptidase A (CoCPD) in their solution and crystalline forms using the X-ray absorption fine structure (XAFS) technique has been conducted. The first coordination sphere of Zn for ZnCPD in its solution state is found to consist of two distributions of atoms, with four atoms (N or O) located at an average distance of 2.03 +/- 0.01 A and one atom (N or O) located at 2.57 +/- 0.04 A. The four-atom distribution remains the same for ZnCPD in its crystalline state, but the fifth atom is found at 2.36 +/- 0.04 A. Examination of the higher coordination shell, between 2.7 and 4.2 A, reveals the presence of two imidazoles. Combined with X-ray crystallographic results, a structural model is proposed. The four atoms at an average distance of 2.03 A are assigned to the two delta 1 nitrogens of His-69 and His-196, one epsilon 1 oxygen of Glu-72, and the oxygen of a coordinated water molecule. The atom at 2.57 A for ZnCPD in solution is assigned to the epsilon 2 oxygen of Glu-72. The results for CoCPD in solution are similar with the four atoms at an average distance of 2.08 +/- 0.01 A and one atom at 2.50 +/- 0.04 A, which moves to 2.34 +/- 0.04 A in the crystalline enzyme. The intensity of the 3d "pip" peak for CoCPD is consistent with a distorted tetragonal metal geometry for the solution form of the enzyme which is converted to a more pentacoordinated metal site for the crystalline enzyme. The first shell distribution of crystalline CoCPD is quite disordered, which may be largely due to the disorder of His-69 and His-196 as indicated by higher shell analysis. Thus, the XAFS studies show that the metal coordination spheres in the zinc and cobalt enzymes are quite similar in the solution state but differ from their crystalline counterparts. The XAFS studies provide the necessary background for measurement of substrate- and inhibitor-promoted structural changes in the metal coordination sphere of the zinc and other metal-substituted carboxypeptidases in the solution state. PMID- 1734964 TI - pH dependence of the interaction of hirudin with thrombin. AB - The kinetics of the inhibition of human alpha-thrombin by recombinant hirudin have been studied over the pH range from 6 to 10. The association rate constant for hirudin did not vary significantly over this pH range. The dissociation constant of hirudin depended on the ionization state of groups with pKa values of about 7.1, 8.4, and 9.2. Optimal binding of hirudin to thrombin occurred when the groups with pKa values of 8.4 and 9.0 were protonated and the other group with a pKa of 7.1 was deprotonated. The pH kinetics of genetically engineered forms of hirudin were examined in an attempt to assign these pKa values to particular groups. By using this approach, it was possible to show that protonation His51 and ionization of acidic residues in the C-terminal region of hirudin were not responsible for the observed pKa values. In contrast, the pKa value of 8.4 was not observed when a form of hirudin with an acetylated alpha-amino group was examined, and, thus, this pKa value was assigned to the alpha-amino group of hirudin. The requirement for this group to be protonated for optimal binding to thrombin is discussed in terms of the crystal structure of the thrombin-hirudin complex. Examination of this structure allowed the other pKa values of 7.1 and 9.2 to be tentatively attributed to His57 and the alpha-amino group of Ile16 of thrombin. PMID- 1734965 TI - Expression and mutagenesis of thrombospondin. AB - Thrombospondin is a 420,000-dalton adhesive glycoprotein that is composed of three subunits of equivalent molecular weight. When the cDNA for the complete coding region of the human endothelial cell thrombospondin subunit is expressed in mouse NIH 3T3 cells, a 420,000-dalton protein is synthesized and secreted. The expressed protein comigrates with human platelet thrombospondin both in the presence and in the absence of a reducing agent. The expressed protein binds to a monoclonal anti-thrombospondin antibody, heparin, and calcium. In addition to the 420,000-dalton protein, the transfected cell lines also express a variable amount of a 140,000-dalton polypeptide. When the culture supernatants that are produced by cells that are expressing thrombospondin are applied to heparin-Sepharose, the 420,000-dalton and the 140,000-dalton proteins are bound to the column and are eluted with buffer containing 0.55 and 0.3 M NaCl, respectively. The 140,000 dalton protein only binds to heparin-Sepharose in the presence of calcium. Deletion of the region of homology with procollagen results in defective assembly of the trimer. Deletion of the type 1 or type 2 repeats results in decreased stability of the subunit with the predominant polypeptides that are expressed having molecular weights of 127,000 and 130,000, respectively. These polypeptides retain low-affinity heparin-binding activity. High-affinity heparin binding is markedly diminished by mutations in either of two sequence motifs that include clusters of lysines and arginines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1734966 TI - Interaction between the heavy and the regulatory light chains in smooth muscle myosin subfragment 1. AB - The interaction between the heavy and the regulatory light chains within chicken gizzard myosin heads was investigated by using a zero-length chemical cross linker, 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide (EDC). The chicken gizzard subfragment 1 (S-1) used was treated with papain so that the heavy chain was partly cleaved into the NH2-terminal 72K and the COOH-terminal 24K fragments and the regulatory light chain into the 16K fragment. S-1 was reacted with EDC either alone or in the presence of ATP or F-actin. In all cases, the 16K fragment of the regulatory light chain formed a covalent cross-link with the 24K heavy chain fragment but not with the 72K fragment. The 38K cross-linked peptide, which was the product of cross-linking between the 16K light chain and the 24K heavy chain fragments, was isolated and further cleaved with cyanogen bromide and arginylendopeptidase. Smaller cross-linked peptides were purified by reverse phase HPLC and then characterized by amino acid analysis and sequencing. The results indicated that cross-linking occurred between Lys-845 in the heavy chain and Asp-168, Asp-170, or Asp-171 in the regulatory light chain. The position of the cross-linked lysine was only three amino acid residues away from the invariant proline residue mapped as the S-1-rod hinge by McLachlan and Karn [McLachlan, A. D., & Karn, J. (1982) Nature (London) 299, 226-231]. We propose that the COOH-terminal region of the regulatory light chain is located in the neck region of myosin and that this region and the phosphorylation site of the regulatory light chain together may play a role in the phosphorylation-induced conformational change of gizzard myosin. PMID- 1734967 TI - Posttranslational modification of Klebsiella pneumoniae flavodoxin by covalent attachment of coenzyme A, shown by 31P NMR and electrospray mass spectrometry, prevents electron transfer from the nifJ protein to nitrogenase. A possible new regulatory mechanism for biological nitrogen fixation. AB - A strain of Escherichia coli (71-18) that produces ca. 15% of its soluble cytoplasmic protein as a flavodoxin, the Klebsiella pneumoniae nifF gene product, has been constructed. The flavodoxin was purified using FPLC and resolved into two forms, designated KpFldI and KpFldII, which were shown to have identical N terminal amino acid sequences (30 residues) in agreement with that predicted by the K. pneumoniae nifF DNA sequence. 31P NMR, electrospray mass spectrometry, UV visible spectra, and thiol group estimations showed that the single cysteine residue (position 68) of KpFldI is posttranslationally modified in KpFldII by the covalent, mixed disulfide, attachment of coenzyme A. KpFldII was inactive as an electron carrier between the K. pneumoniae nifJ product (a pyruvate-flavodoxin oxidoreductase) and K. pneumoniae nifH product (the Fe-protein of nitrogenase). This novel posttranslational modification of a flavodoxin is discussed in terms of the regulation of nitrogenase activity in vivo in response to the level of dissolved O2 and the carbon status of diazotrophic cultures. PMID- 1734968 TI - Sequential resonance assignments of oxidized high-potential iron-sulfur protein from Chromatium vinosum. AB - 2D NMR spectra of the high-potential iron-sulfur protein (HiPIP) from Chromatium vinosum have been used to obtain partial resonance assignments for the oxidized paramagnetic redox state of the protein. Sequence-specific assignments were made using NOESY and COSY spectra in H2O and D2O of the following backbone segments: Asn-5-Arg-33, Glu-39-Asp-45, Gly-55-Cys-63, Gly-68-Ala-78, and Leu-82-Gly-85. NOESY spectra with a spectral width wide enough to include the hyperfine-shifted resonances revealed numerous NOE contacts between these signals and those in the main envelope of the proton spectrum. With the aid of the X-ray crystal structure [Carter, C.W., Kraut, J., Freer, S. T., Xuong, N. H., Alden, R. A., & Bartsch, R. G. (1974) J. Biol. Chem. 249, 4212], these NOEs permitted seven of the nine hyperfine-shifted signals to be assigned to three of the cysteine residues liganded to the metal cluster (Cys-43, Cys-46, and Cys-77). The other two hyperfine-shifted signals produced no detectable NOEs to other resonances in the spectrum and were tentatively assigned to the remaining cysteinyl ligand (Cys 63). These assignments, in conjunction with recent theoretical models of the electronic structure of the Fe4S4 cluster [Noodleman, L. (1988) Inorg. Chem. 27, 3677; Bertini, I., Briganti, F., Luchinat, C., Scozzafava, A., & Sola, M. (1991) J. Am. Chem. Soc. 113, 1237], indicate that the iron atoms coordinated to Cys-63 and Cys-77 are those of the mixed-valence Fe(3+)-Fe2+ pair whereas Cys-43 and Cys 46 are ligands to the Fe(3+)-Fe3+ metal pair. PMID- 1734969 TI - Sequence-specific 1H NMR assignments and solution structure of bovine pancreatic polypeptide. AB - Sequence-specific 1H NMR assignments for the 36 residue bovine pancreatic polypeptide (bPP) have been completed. The secondary and tertiary structure of bPP in solution has been determined from experimental NMR data. It is shown that bPP has a very well-defined C-terminal alpha-helix involving residues 15-32. Although regular secondary structure cannot be clearly defined in the N-terminal region, residues 4-8 maintain a rather ordered conformation in solution. This is attributed primarily to the hydrophobic interactions between this region and the C-terminal helix. The two segments of the structure are joined by a turn which is poorly defined. The four end residues both at the N-terminus and the C-terminus are highly disordered in solution. The overall fold of the bPP molecule is very closely similar to that found in the crystal structure of avian pancreatic polypeptide (aPP). The RMS deviation for backbone atoms of residues 4-8 and 15-32 between the bPP mean structure and the aPP crystal structure is 0.65 A, although there is only 39% identity of the residues. Furthermore, the average conformations of some (mostly from the alpha-helix) side chains of bPP in solution are closely similar to those of aPP in the crystal structure. A large number of side chains of bPP, however, show significant conformational averaging in solution. PMID- 1734970 TI - Assignment of the 1H NMR spectrum and secondary structure elucidation of the single-stranded DNA binding protein encoded by the filamentous bacteriophage IKe. AB - By means of 2D NMR techniques, all backbone resonances in the 1H NMR spectrum of the single-stranded DNA binding protein encoded by gene V of the filamentous phage IKe have been assigned sequence specifically (at pH 4.6, T = 298 K). In addition, a major part of the side chain resonances could be assigned as well. Analysis of NOESY data permitted the elucidation of the secondary structure of IKe gene V protein. The major part of this secondary structure is present as an antiparallel beta-sheet, i.e., as two beta-loops which partly combine into a triple-stranded beta-sheet structure, one beta-loop and one triple-stranded beta sheet structure. It is shown that a high degree of homology exists with the secondary structure of the single-stranded DNA binding protein encoded by gene V of the distantly related filamentous phage M13. PMID- 1734971 TI - Transition-state characterization: a new approach combining inhibitor analogues and variation in enzyme structure. AB - A new strategy of potentially broad application for probing transition-state (TS) analogy in enzymatic systems is described in this paper. The degree to which a series of phosphonate inhibitors act as TS analogues of rat carboxypeptidase A1 has been determined for the wild-type enzyme, for the R127K, R127M, and R127A mutants, and for the R127A mutant in the presence of 0.5 M guanidine hydrochloride. The impact that the mutations have on the inverse second-order rate constants (Km/kcat) for substrate hydrolysis is mirrored by the effect on the inhibition constants (Ki) for the corresponding phosphonate inhibitors. These results demonstrate that the phosphonate moiety mimics some of the electronic as well as the geometric characteristics of the TS. A similar but distinctly separate correlation is observed for tripeptide analogues in comparison to analogues of the dipeptide Cbz-Gly-Phe, reflecting an anomalous mode of binding for the latter system. The selective rate increases and corresponding enhancement in inhibitor binding observed on addition of 0.5 M guanidine hydrochloride to the R127A mutant indicate that the exogenous cation can assume the role played by Arg 127 in stabilizing the TS and in providing substrate selectivity at the P2 position. PMID- 1734972 TI - Primary structure of the Thermoplasma proteasome and its implications for the structure, function, and evolution of the multicatalytic proteinase. AB - The proteasome or multicatalytic proteinase is a high molecular mass multisubunit complex ubiquitous in eukaryotes but also found in the archaebacterial proteasome is made of two different subunits only, and yet the complexes are almost identical in size and shape. Cloning and sequencing the gene encoding the small (beta) subunit of the T. acidophilum complex completes the primary structure of the archaebacterial proteasome. The similarity of the derived amino acid sequences of 233 (alpha) and 211 (beta) residues, respectively, indicates that they arose from a common ancestral gene. All the sequences of proteasomal subunits from eukaryotes available to date can be related to either the alpha subunit or beta-subunit of the T. acidophilum "Urproteasome", and they can be distinguished by means of a highly conserved N-terminal extension, which is characteristic for alpha-type subunits. On the basis of circumstantial evidence we suggest that the alpha-subunits have regulatory and targeting functions, while the beta-subunits carry the active sites. PMID- 1734973 TI - Recognition of tertiary structure in tRNAs by Rh(phen)2phi3+, a new reagent for RNA structure-function mapping. AB - With photoactivation Rh(phen)2phi3+ promotes strand cleavage at sites of tertiary interaction in tRNA. The rhodium complex, which binds double-helical DNA by intercalation in the major groove, yields no cleavage in double-helical regions of the RNA or in unstructured single-stranded regions. Instead, Rh(phen)2phi3+ appears to target regions which are structured so that the major groove is open and accessible for stacking with the complex, as occurs where bases are triply bonded. So as to examine the specificity of this novel reagent and to evaluate its use in probing structural changes in RNAs, cleavage studies have been conducted on two structurally characterized tRNAs, tRNA(Phe) and tRNA(Asp) from yeast, the unmodified yeast tRNA(Phe) transcript, and a chemically modified tRNA(Phe), as well as on a series of tRNA(Phe) mutants. On tRNA(Phe) strong cleavage is observed at residues G22, G45, U47, psi 55, and U59; weaker cleavage is observed at A44, m7G46, and C48. On tRNA(Asp) cleavage is found at residues A21 through G26, psi 32, and U48, with minor cleavage apparent at A44, G45, A46, psi 55, U59, and U60. There is a striking similarity in cleavage observed on these tRNAs, and the sites of cleavage mark regions of tertiary folding. Cleavage on the unmodified tRNA(Phe) transcript resembles closely that found on native yeast tRNA(Phe), but additional sites, primarily in the anticodon loop and stem, are evident. The results indicate that globally the structures containing or lacking the modified bases appear to be the same; the differences in cleavage observed may reflect a loosening or alteration in the structure due to the absence of the modified bases. Cleavage results on mutants of tRNA(Phe) illustrate Rh(phen)2phi3+ as a sensitive probe in characterizing tRNA tertiary structure. Results are consistent with other assays for structural or functional changes. Uniquely, Rh(phen)2phi3+ appears to target directly sites of tertiary interaction. Cleavage results on mutants which involve base changes within the triply bounded region of the molecule indicate that it is the structure of the triply bonded array rather than the individual nucleotides which are being targeted. Chemical modification to promote selective depurination of the third base (m7G46) involved in the triple in the folded, native tRNA leads to the reduction of cleavage by the metal complex; this result shows directly the importance of the stacked triple base structure for recognition by the metal complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1734974 TI - A segment-based approach to protein secondary structure prediction. AB - Amino acid sequence patterns have been used to identify the location of turns in globular proteins [Cohen et al. (1986) Biochemistry 25, 266-275]. We have developed sequence patterns that facilitate the prediction of helices in all helical proteins. Regular expression patterns recognize the component parts of a helix: the amino terminus (N-cap), the core of the helix (core), and the carboxy terminus (C-cap). These patterns recognize the core features of helices with a 95% success rate and the N- and C-capping features with success rates of 56% and 48%, respectively. A metapattern language, ALPPS, coordinates the recognition of turns and helical components in a scheme that predicts the location and extent of alpha-helices. On the basis of raw residue scoring, a 71% success rate is observed. By focusing on the recognition of core helical features, we achieve a 78% success rate. Amended scoring procedures are presented and discussed, and comparisons are made to other predictive schemes. PMID- 1734975 TI - Three-dimensional structure of soybean trypsin/chymotrypsin Bowman-Birk inhibitor in solution. AB - The three-dimensional structure of soybean trypsin/chymotrypsin Bowman-Birk inhibitor in solution has been determined by two-dimensional 1H nuclear magnetic resonance spectroscopy and dynamical simulated annealing using the program XPLOR. The structure was defined by 907 NOEs involving intra- and interresidue contacts which served as distance constraints for a protocol of dynamical simulated annealing. In addition, 48 phi angle constraints involving non-proline amino acids, 29 chi angle constraints, six omega angle constraints for the X-Pro peptide bond, and 35 stereoassignments for prochiral centers were incorporated during the course of the calculation. The protein is characterized by two distinct binding domains for serine protease. Each domain is comprised of a beta hairpin (antiparallel beta-sheet and a cis-proline-containing type VIb reverse turn) with a short segment making a third strand of antiparallel beta-sheet. The structure determination and refinement are described, and the structure is compared to other structures of Bowman-Birk inhibitors as well as other families of serine protease inhibitors. PMID- 1734976 TI - A marketing plan for the nineties. PMID- 1734977 TI - Structured skin care regimen to prevent perineal dermatitis in the elderly. AB - A preliminary investigation was conducted to determine the efficacy of a structured skin care regimen to prevent perineal dermatitis in incontinent geriatric psychiatry patients. A 10-week, prospective, clinical trial was conducted (n = 15). Four weeks (weeks 2 to 5) were devoted to monitoring the unstructured pretreatment nursing skin care practice and to determining the incidence of perineal dermatitis in incontinent patients. Four weeks (weeks 7 to 10) were also spent implementing and observing the structured nursing skin care regimen. The study revealed that 33% (three) of the subjects in the unstructured skin care group and 33% (two) of the subjects in the structured skin care group had perineal dermatitis. In subjects with a combination of urine and stool incontinence perineal dermatitis developed within 2 days. The findings suggest that perineal dermatitis occurs quickly in the presence of urine and stool incontinence. Further research is needed to validate the efficacy of a structured skin care regimen to prevent perineal dermatitis. PMID- 1734978 TI - Infection in the cancer patient with an ostomy. AB - One of the most common reasons for ostomy surgery today is cancer. Because cancer is frequently treated with combined therapy, the surgery that results in an ostomy may be only one component of the overall therapy. The ET nurse is frequently the only nurse who cares for the patient on a consistent basis as he or she crosses medical-surgical therapies, and the ET nurse may be the one to first notice changes in the patient. Knowledge of the increased risks of infection and methods of prevention and therapeutic approaches are critical to the care of a patient who is undergoing such therapy. PMID- 1734980 TI - Bowel and bladder management in a child. PMID- 1734979 TI - Collaborative atmosphere: rectal pouching in the burn center. AB - Collaborative practice between nursing specialties opens up opportunities for expanded and improved quality care. Rectal pouching in the burn center is one of these options; it was used in this case with a patient who received cultured epithelial autograft. Pouching practices from the literature are reviewed. A description of rectal pouching to provide stool containment and protection of the wound bed is detailed. Problems with the pouching procedure and potential solutions are also discussed. A summary statement of this highly successful method of stool containment, which is used to guard against wound infection, concludes the article. PMID- 1734981 TI - "ET" and the elderly. PMID- 1734982 TI - Persons who have stomas: violent injury versus disease. AB - Victims of violence may have injuries that necessitate the construction of stomas. The purposes of this retrospective study were to (1) describe demographic and perioperative variables for persons who had fecal stomas as a result of violent injury and (2) to compare these variables with those for persons who had stoma construction because of disease. Medical records of 44 persons who had stoma construction performed at a level I trauma center were reviewed. Victims of violence (n = 26) were generally young, black men with minimal income and no health insurance. Stomas were primarily colostomies of varied construction. Incisions were left open to heal by second intention. Violent behavior is an important cause of injury-related disability in the United States. ET nurses have important roles in teaching, in providing emotional support, and in participating in discharge planning for a patient who has a stoma that is a result of violent injury. PMID- 1734983 TI - Antidiarrhoeal drugs for acute diarrhoea in children. PMID- 1734984 TI - Psychological aspects of lower urinary tract infections in women. AB - OBJECTIVE: To determine whether women with the urethral syndrome can be distinguished from those with urinary tract infection by case notes, clinical symptoms, or psychiatric state. DESIGN: Longitudinal survey of consecutive women presenting with dysuria and frequency. SETTING: General practice and community. SUBJECTS: 58 patients with the urethral syndrome and 44 patients with a urinary tract infection, mean age 39.9 years. MAIN OUTCOME MEASURES: Results of analysis of serial midstream urine specimens, patients' self rated physical symptoms and responses to 60 item general health questionnaire at presentation and after resolution of symptoms, and results of psychiatric assessment with the clinical psychiatric interview. RESULTS: 4 of 42 patients with a urinary tract infection had recently changed sexual partner compared with none of 58 with the urethral syndrome. Dysuria and nocturia were more common in patients with urinary tract infections than those with the urethral syndrome (mean (SD) score for dysuria 5.37 (2.39) v 4.57 (2.13), p less than 0.05; nocturia in 39/44 (88%) patients v 40/58 (69%), chi 2 = 5.5, p less than 0.02). Both groups showed transient high levels of distress which resolved with the physical symptoms, but no psychiatric difference distinguished them. CONCLUSION: The urethral syndrome is not associated with increased psychiatric morbidity. PMID- 1734985 TI - Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study. AB - OBJECTIVE: To study insulin dependent diabetic patients for change in non proliferative retinopathy and its relation to glycaemic control and to various clinical background data. DESIGN: Prospective study with follow up for seven years. SETTING: Outpatient departments of university hospitals. MAIN OUTCOME MEASURES: Glycated haemoglobin concentration; degree of retinopathy. RESULTS: Retinopathy worsened by an overall increase in counts of microaneurysms and haemorrhages from 17 (SD 25) to 45 (58) (p = 0.005). Intensified insulin treatment and home blood glucose monitoring improved concentrations of glycated haemoglobin (HbA1) from 11.2% (2.2%) at the start of the study to a mean of 9.5% (1.5%) over the seven years of the study (p less than 0.0001). A mean value for HbA1 greater than 10% was associated with an increased risk of progression of retinopathy and a mean value less than 8.7% was associated with a diminished risk. Multiple regression analysis identified four independent variables as indicative of outcome of retinopathy after seven years: HbA1 value at baseline; the change in HbA1 from start to the mean level through the seven years; duration of diabetes; and retinopathy at start. Age, blood pressure, and urinary albumin excretion were not related to the presence or progression of retinopathy. CONCLUSION: Secondary intervention by long term lowering of glycated haemoglobin has a beneficial impact on non-proliferative retinopathy. A four factor regression model can determine patients at high risk of severe retinopathy. PMID- 1734986 TI - Voice after laryngectomy. PMID- 1734987 TI - Blood pressure in first 10 years of life: the Brompton study. AB - OBJECTIVES: To determine the normal range of blood pressure and its pattern of change in the first 10 years of life. To estimate at what age (if any) children consistently appear in one part of the blood pressure distribution and at what age familial correlations in blood pressure become significant. DESIGN: Longitudinal cohort study. SETTING: South east England. SUBJECTS: 2088 children of both sexes born consecutively in Farnborough Hospital, Kent, and their parents. MAIN OUTCOME MEASURE: Blood pressure measured by Doppler ultrasonography and sphygmomanometry. RESULTS: Systolic blood pressure rose from a mean of 88.5 mm Hg at age 6 months to 96.2 mm Hg at 8 years measured with a 8 cm cuff and from 89.1 mm Hg at age 5 years to 94.3 mm Hg at age 10 years measured with a 12 cm cuff. The larger cuff gave blood pressure readings about 6 mm Hg lower. This effect was independent of body weight and arm circumference. Diastolic blood pressure rose from 57.8 mm Hg at 5 years to 61.8 mm Hg at 10 years (12 cm cuff). There was only about 1 mm Hg difference between sexes. Blood pressure was correlated with weight, weight adjusted for height, height, and arm circumference at all ages studied. The correlation coefficient of repeated yearly measurements increased steadily with age from 0.28 at 2 years to 0.59 at 10 years. The correlation coefficients between child's blood pressure and mother's average blood pressure increased from 0.1 at age 1 year to 0.23 at age 10. CONCLUSIONS: Blood pressure changes relatively little between the ages of 6 months and 10 years. Yet because of the increasing strength of between occasion and family correlations, children are more consistently occupying a specific part of the blood pressure distribution as they grow older. Studies in children should help determine why some adults have hypertension and others do not. PMID- 1734988 TI - Homozygous haemoglobin O disease and conjugated hyperbilirubinaemia in a Sudanese family. PMID- 1734989 TI - Side of origin of epithelial ovarian cancer. PMID- 1734990 TI - School attendance as a factor in deliberate self poisoning by 12-15 year old adolescents. PMID- 1734991 TI - Prescribing at the hospital-general practice interface. I: Hospital outpatient dispensing policies in England. AB - OBJECTIVE: To describe the outpatient dispensing policies of major acute hospitals in England. DESIGN: Postal questionnaire survey in November 1990. SETTING: All (278) major acute hospitals in England with more than 250 beds, excluding maternity, paediatric, or psychiatric hospitals; nine hospitals declined. PARTICIPANTS: Hospital chief pharmacists. MAIN OUTCOME MEASURES: Current dispensing policy and exceptions to it; when the policy was formed; and who was involved in its formation. RESULTS: Completed questionnaires were received from 200 (72%) of the hospitals approached. The quantities of drugs dispensed to outpatients ranged from zero in 12 hospitals to unlimited amounts in nine; nearly half (92) dispensed a 14 days' supply of drugs. The greater the restriction on outpatient dispensing, the more recently the policy had been introduced (chi 2 for trend = 7.15; df = 1; p less than 0.01). Permissible exceptions to the policy included the consultant's specific request (134 hospitals), difficulty in obtaining drugs in the community (102), urgent need for start of treatment (49), and certain types of patients (41) or drugs or their regimens (104). Groups who were neither represented on the hospital committee concerned with policy formation nor consulted before policy changes included regional health authorities in 122 hospitals, district health authorities in 101 hospitals, and general practitioners in 32 hospitals. CONCLUSIONS: Outpatient dispensing policies varied considerably among the hospitals surveyed, but they seemed to be moving towards greater restrictions on the supply of drugs given to outpatients. PMID- 1734992 TI - Failed hip replacements. PMID- 1734994 TI - Prescribing at the interface between hospitals and general practitioners. PMID- 1734993 TI - Prescribing at the hospital-general practice interface. II: Impact of hospital outpatient dispensing policies in England on general practitioners and hospital consultants. AB - OBJECTIVE: To assess the impact on general practitioners and hospital consultants of hospital outpatient dispensing policies in England. DESIGN: Postal questionnaire and telephone interview survey of general practitioners and hospital consultants in January 1991. SETTING: 94 selected major acute hospitals in England. PARTICIPANTS: 20 general practitioners in the vicinity of each of 94 selected hospitals and eight consultants from each, selected by chief pharmacists. MAIN OUTCOME MEASURES: Proportions of general practitioners unable to assume responsibility for specialist drugs and of consultants wishing to retain responsibility; association between dispensing restrictions and the frequency of general practitioners being asked to prescribe hospital initiated treatments. RESULTS: Completed questionnaires were obtained from 1207 (64%) of 1887 general practitioners and 457 (63%) of 729 consultants. 570 (46%) general practitioners felt unable to take responsibility for certain treatments, principally because of difficulty in detecting side effects (367, 30%), uncertainty about explaining treatment to patients (332, 28%), and difficulty monitoring dosage (294, 24%). Among consultants 328 (72%) wished to retain responsibility, principally because of specialist need for monitoring (93, 20%), urgent need to commence treatment (64, 14%), and specialist need to initiate or stabilise treatment (63, 14%). The more restricted the drug supply to outpatients, the more frequently consultants asked general practitioners to prescribe (p less than 0.01) and complete a short course of treatment initiated by the hospital (p less than 0.001). CONCLUSIONS: Restrictive hospital outpatient dispensing shifts clinical responsibility on to general practitioners. Hospital doctors should be able to retain responsibility for prescribing when the general practitioner is unfamiliar with the drug or there is a specialist need to initiate, stabilise, or monitor treatment. PMID- 1734995 TI - Medical education. PMID- 1734996 TI - Transport: a public health issue. PMID- 1734997 TI - Unstable asthma and theophylline. PMID- 1734998 TI - Medically unexplained physical symptoms. PMID- 1734999 TI - Passive smoking and otitis media with effusion. PMID- 1735000 TI - Preventing AIDS now. PMID- 1735001 TI - Case definitions for AIDS surveillance in Africa. PMID- 1735002 TI - Chorionic villus sampling. PMID- 1735003 TI - Preventing AIDS now. PMID- 1735004 TI - Genitourinary tract infections in pregnancy and low birth weight. PMID- 1735005 TI - More oncologists, please. PMID- 1735006 TI - Unemployment rates: an alternative to the Jarman index? PMID- 1735007 TI - The health of Europe. PMID- 1735008 TI - Euthanasia around the world. PMID- 1735009 TI - Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. AB - A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0 1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation. PMID- 1735010 TI - Phase I-II trial of high-dose melphalan in previously untreated stage III multiple myeloma: Cancer and Leukemia Group B study 8512. AB - To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-II trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients achieved complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2 achieved CR. Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival. PMID- 1735011 TI - Use of recombinant human interleukin-2 in conjunction with bone marrow transplantation as a model for control of minimal residual disease in malignant hematological disorders: I. Treatment of murine leukemia in conjunction with allogeneic bone marrow transplantation and IL-2-activated cell-mediated immunotherapy. AB - Immunotherapy with recombinant human interleukin-2 (IL-2) and allogeneic spleen cells has led to significant antitumor effects in B-cell leukemia- (BCL1) bearing mice following transplantation with T-lymphocyte-depleted allogeneic bone marrow cells. Graft versus leukemia (GVL) effects were studied in a model mimicking minimal residual disease following bone marrow transplantation (BMT). Lethally irradiated (BALB/c x C57BL/6)F1 recipients were reconstituted with 20 x 10(6) T lymphocyte-depleted C57BL/6 bone marrow cells mixed with 10(4) to 10(6) BCL1 cells followed by administration of sequential increments of allogeneic C57BL/6 spleen cells; 10(6) cells on Day +1, 10(7) cells on Day +5, and 5 x 10(7) cells on Day +9, with or without concomitant IL-2 treatment (intraperitoneal injections of 20,000 U twice daily for 3 days) together with each spleen cell administration. All mice receiving 10(4)-10(6) BCL1 cells developed marked splenomegaly by Day +21 and all adoptive recipients of 10(5) spleen cells obtained from these mice developed leukemia within 21-36 days. Treatment of mice which received 10(4) BCL1 cells by either three courses of low dose IL-2 or three increments of allogeneic spleen cells alone and certainly by a combination of both resulted in normalization of splenomegaly on Day +21, but only adoptive recipients of 10(5) spleen cells obtained from mice treated by both allogeneic spleen cells and IL-2 (10/10) or allogeneic spleen cells alone (8/10) were disease free (greater than 100 days). Mice inoculated with 10(5) BCL1 cells developed mild splenomegaly on Day +21 after IL2 treatment alone, but showed no clinical evidence of disease following administration of allogeneic spleen cells or both allogeneic spleen cells and IL-2. Following adoptive transfer of 10(5) spleen cells obtained from each treated group no leukemia (greater than 100 days) was evident in recipients of spleen cells obtained from mice treated with both allogeneic spleen cells and IL-2 (10/10) whereas a partial effect was observed in mice treated by allogeneic spleen cells only (4/10). Mice inoculated with a high dose of BCL1 cells (10(6] showed some delay in onset of splenomegaly, but no curative antileukemic effects could be observed even following a synergistic combination of IL-2 and allogeneic spleen cells. Our data suggest that immunocompetent allogeneic lymphocytes may play an important role against leukemic relapse and thus cell therapy may be used therapeutically to treat minimal residual disease after BMT even following initial reconstitution with T cell-depleted bone marrow cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735013 TI - Patenting life. PMID- 1735012 TI - Pseudomonas aeruginosa infection in cancer patients. AB - Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735014 TI - New developments in protein isolation, purification, and characterization. AB - The most significant advancements in techniques and methods for protein purification and analysis have been made in liquid chromatography and in electrophoresis. In the area of chromatography, adsorbents based on new affinity principles have been prepared. New packing materials have facilitated the rapid progress of high-performance techniques. A great many new techniques in the field of electrophoresis have emerged. On an analytical scale, electrophoretic methods in two dimensions or in capillaries are unsurpassed in resolution power. Development of techniques for protein transfer between different media is a prerequisite for a full exploitation of the new methods. Modern techniques for analysis of submicrogram quantities facilitate the separation, detection, and characterization of complex protein mixtures. PMID- 1735015 TI - Is more better? PMID- 1735016 TI - Acute renal failure. PMID- 1735017 TI - Acute tubular necrosis: differences between oliguria and nonoliguria. PMID- 1735018 TI - Diuretic and vasopressor usage in acute renal failure: a synopsis. PMID- 1735019 TI - Hyperkalemic emergencies. PMID- 1735020 TI - Dialysis options in the critically ill patient: hemodialysis, peritoneal dialysis, and continuous renal replacement therapy. PMID- 1735021 TI - SCUF/CAVH/CAVHD: critical differences. PMID- 1735022 TI - Neonatal peritoneal dialysis in acute renal failure. PMID- 1735023 TI - Dialysis in the pediatric intensive care unit: a case study. PMID- 1735024 TI - Dialysis in the surgical intensive care patient: a case study. PMID- 1735025 TI - Comparison of search strategies on CD Plus/MEDLINE. PMID- 1735026 TI - Primum non nocere. PMID- 1735027 TI - Low-osmolarity contrast media. PMID- 1735028 TI - Understanding psychotropic drugs. PMID- 1735029 TI - Interchangeability of oral contraceptive products. PMID- 1735030 TI - Guidelines for a phlebotomy chair. PMID- 1735031 TI - Call display: a telephone disservice. PMID- 1735032 TI - Call Display: a telephone disservice. PMID- 1735033 TI - Laughing all the way to the bank. PMID- 1735034 TI - Canadian Coordinating Office for Health Technology Assessment. PMID- 1735035 TI - The "overpass syndrome". PMID- 1735036 TI - The fight against tobacco: sustaining the momentum. PMID- 1735037 TI - Intravenous immune globulin use in children. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 1735038 TI - Advance directives: are they an advance? Advance Directives Seminar Group, Centre for Bioethics, University of Toronto. PMID- 1735039 TI - Snowmobile-related deaths in Ontario: a 5-year review. AB - OBJECTIVES: To investigate the demographic characteristics and circumstances surrounding fatal snowmobile accidents in Ontario, to examine the risk factors and to observe any fatality trends over the study period. DESIGN: Case series. PATIENTS: All 131 people who died accidentally while operating a snowmobile in Ontario from 1985-86 to 1989-90. Records were obtained from the chief coroner's office; registration data were obtained from the Ministry of Transportation. RESULTS: Although the absolute number of deaths increased each year, owing to a rapid increase in the number of registered snowmobiles, the risk of death from snowmobile accidents remained relatively constant. Deaths occurred most frequently in northeastern Ontario. Youths and men predominated among the victims. Fatal accidents occurred more often on lakes (in 66% of the cases in which this information was known) than on roads (in 26%) or trails (in 8%). Weekend fatalities predominated, and deaths occurred most often during times of suboptimal lighting (from 4 pm to 8 am). The driver was killed in 84% of the cases in which the person's role was known. Alcohol use before death was implicated in 69% of the cases, the level exceeding the Ontario legal limit in 59%. CONCLUSION: Snowmobile-related deaths result from factors that are generally avoidable. Strategies need to be instituted to reduce the rate of these events. PMID- 1735040 TI - A survey of medical quality assurance programs in Ontario hospitals. AB - OBJECTIVE: To determine the prevalence and types of medical quality assurance practices in Ontario hospitals. DESIGN: Survey. SETTING: All teaching, community, chronic care, rehabilitation and psychiatric hospitals that were members of the Ontario Hospital Association as of May 1990. PARTICIPANTS: The person deemed by the chief executive officer of each hospital to be most responsible for medical administration. INTERVENTION: A questionnaire to obtain information on each hospital's use of criteria audit, indicators inventory, occurrence screening and reporting, and utilization review and management (URM) activities. OUTCOME MEASURES: Prevalence of the use of the quality assurance activities, the people responsible for the activities and the relative success of the URM program in modifying physicians' performance. RESULTS: Of the 245 member hospitals participants from 179 (73%) responded. Criteria audits were performed in 136 (76%), indicators inventory in 43 (24%), occurrence screening in 44 (25%), occurrence reporting in 61 (34%) and URM in 123 (69%). In-hospital deaths were reviewed in 157 (88%) of the hospitals. In all, 87 (55%) of the respondents from hospitals that had a URM program or were developing one indicated that their program was successful in modifying physicians' practices, and 29 (18%) reported that it was not successful; 26 (16%) stated that the effect was still unknown, and 16 (10%) did not respond. Seventy (40%) stated that results of tissue reviews were reported at least 10 times per year and 94 (83%) that medical record reviews were reported at least as often. The differences in the prevalence of the quality assurance activities between the hospitals were not found to be significant. CONCLUSIONS: Many Ontario hospitals are conducting a wide variety of quality assurance activities. Further study is required to determine whether the differences in prevalence of these activities between hospitals would be significant in a larger, perhaps national, sample. Strategies are needed to ensure universal involvement and participation in the improvement of the quality of care and the assessment of the cost-effectiveness of health care treatments. Recommendations to achieve these objectives are suggested. PMID- 1735041 TI - Coronary artery bypass grafting: how much does it cost? AB - OBJECTIVE: To calculate the cost of coronary artery bypass grafting (CABG) and to compare it with the costs determined in two previous Canadian studies. DESIGN: Retrospective cost-analysis study. SETTING: A tertiary care referral hospital. PATIENTS: Fifty patients who had undergone successful triple and quadruple CABG between Jan. 3 and 30, 1989. MAIN RESULTS: The cost of CABG per patient varied from $10,982 to $33,676 (mean $14,328) (in 1988 Canadian dollars). The cost tended to increase with age and number of vessels grafted. Compared with the patients in the two previous Canadian studies our patients were older, had more vessels grafted and cost more to treat, even after the total hospital costs were adjusted for inflation. CONCLUSIONS: The population undergoing CABG is changing: it is older and has more diseased vessels. These changes have had a significant impact on the cost of CABG. Further study is required to determine the outcome and benefit of CABG in this group of patients. PMID- 1735042 TI - [Precautions for international travelers]. PMID- 1735043 TI - The patient as interface between genes and the environment. PMID- 1735044 TI - Effect of tobacco smoking on the nervous system. 1921. PMID- 1735045 TI - Tobacco smoke. 1923. PMID- 1735046 TI - Tobacco from a medical point of view. 1926. PMID- 1735047 TI - Modern methods in the treatment of carcinoma. 1930. PMID- 1735048 TI - AIDS court case could lead to higher costs, CMA spokesman warns. PMID- 1735049 TI - Anencephalic infants as organ donors: beware the slippery slope. PMID- 1735050 TI - Ontario seeks solution to chronic shortages of francophone MDs. PMID- 1735051 TI - Toronto-based foundation tries to combat underfunding in women's health research. PMID- 1735052 TI - Canadian Medical Association Policy Summary: maintenance of competence. PMID- 1735053 TI - Medical training in the United States. PMID- 1735054 TI - The vascular history and physical examination. AB - The value of the vascular examination cannot be over-estimated. Symptoms of vascular disease present in the foot and lower extremity may actually be manifestations of severe life-threatening disease. Symptoms, their location, and the frequency and quality of the patient's pain often provide valuable clues for the clinician's diagnosis. Central nervous system symptoms, ocular disturbances, cardiac symptoms, impotence, or constitutional disturbances may all indicate systemic arterial disease. Risk factors for this disease include smoking, hypertension, hyperlipidemia, genetic predisposition, diabetes, emotional stress, and physical inactivity. Those factors attributable to hypercoagulability and venous disease are birth control pill use, estrogen chemotherapy, obesity, prolonged immobilization, paralysis, previous thrombotic episodes, venous stasis disease, and varicose veins. An accurate bilateral assessment of blood pressure, pulses, and capillary perfusion is of critical importance. Careful inspection of the extremity for trophic changes, skin color, texture, temperature, edema, ulceration, atrophy, or paresis, will provide clues of vasculopathy. A relatively accurate assessment of circulatory status may be obtained without the use of exotic instruments. Simple tests such as the elevation and dependency tests, capillary bed return test, venous filling time test, along with blood pressure, pulse, and possibly oscillometry data are valuable in arterial evaluation. Such venous tests as inspection, percussion, Homan's sign, Trendelenburg, and Perthes' tourniquet are useful in the determination of the presence of venous disease. Fortunately, over the past few years tremendous advances have been made in the technology of the vascular laboratory. If symptoms are discovered during the vascular history and physical examination, the complete noninvasive study will provide impressive data to quantitate and specifically establish the diagnosis. PMID- 1735055 TI - Peripheral vascular dis in the lower extremity. PMID- 1735056 TI - Primary podiatric care of the vascularly compromised patient. AB - Primary podiatric care encompasses patient education, disease prevention, diagnosis, treatment, and patient referral. When performed on a regular basis, primary podiatric care can delay or prevent some of the complications associated with the vascularly compromised patient. PMID- 1735057 TI - Diabetes and peripheral vascular disease. AB - The classic Framingham Study suggests that the duration of diabetes is a contributing factor in the development of PVD. The major objective of all podiatric physicians should be to provide patients with the necessary information about the severity of their disease, particularly alerting them that noncompliance may lead to a lower extremity amputation and enlisting them as part of the treatment team in managing their condition. PMID- 1735058 TI - Vasospastic disorders. AB - Any disruption of the lymphatic system, including vessels and nodes, precludes the mobilization of lymph, resulting in the accumulation of colloidal material in the intercellular spaces. This article outlines the lymphatic system development and anatomy, leg lymph composition and flow, and diagnostic approaches and treatment for various forms of primary and secondary lymphedema. PMID- 1735059 TI - Lymphatic diseases. AB - The microcirculation is the keystone of bodily homeostasis. Although it may be altered organically as in arteriolosclerosis and diabetic angiopathy, its unique architecture makes it prone to spasticity. This article discusses vasospasticity and diagnostic approaches and treatment for Raynaud's vasospasticity, acrocyanosis, and livedo reticularis. PMID- 1735060 TI - Smoking and peripheral vascular disease. Podiatric medical update. AB - Although there is strong evidence that cigarette smoking is perhaps the major risk factor associated with peripheral occlusive vascular disease, there still appears to be little indication that clinicians in podiatric medicine and patients recognize this. When smoking is combined with other risk factors such as diabetes mellitus, the probability of developing peripheral arterial disease is greatly increased. In addition, smoking appears to accelerate the natural history of the process of atherogenesis and thrombosis. Diabetic neuropathy seems to have a greater prevalence when the patient has a history of an increased number of pack years smoked. By eliminating smoking, patients can often receive considerable relief from intermittent claudication and other sequelae of occlusive vascular disease, including the avoidance of amputation of the lower extremity. Patient care routinely should include efforts to prevent individuals from smoking as well as advice to smokers to stop. Podiatrists need to become a more prominent source of information about the hazards of smoking and should freely share this knowledge with their patients. PMID- 1735061 TI - Exercise and peripheral vascular disease. AB - The use of exercise as a nonsurgical therapy for peripheral arterial disease has been shown to be effective. Studies have demonstrated improved walking tolerances, alterations in skeletal muscle metabolism, and improved blood distribution with exercise. PMID- 1735062 TI - Evaluation of arterial blood flow in the lower extremity. AB - Podiatrists need to evaluate arterial blood flow to determine whether arterial flow is compatible for healing following a contemplated surgery, to determine whether arterial flow is at a compatible level to prevent tissue necrosis or heal an ischemic ulcer, and to determine whether the patient should be referred to a vascular surgeon for consideration of the possible surgery. This article addresses these needs and provides guidelines to help make these assessments. PMID- 1735063 TI - Invasive diagnostic imaging of the lower extremities. AB - Invasive arterial imaging techniques are crucial to the preoperative evaluation of patients requiring arterial surgery. Venography is important in patients who are candidates for venous reconstruction, and it is also useful in the difficult diagnosis of deep venous thrombosis. The authors discuss the development of angiographic techniques, indications for use, patient preparation, and potential complications. Several examples of these tests are illustrated. PMID- 1735064 TI - Lower extremity arterial occlusive disease. AB - The clinician must first understand the natural history of chronic lower extremity ischemia before making a decision regarding therapeutic options. Clearly, mild ischemia as evidenced by claudication does not place the patient at significant risk for limb loss. Initial conservative treatment emphasizing abstinence from tobacco products, control of underlying medical maladies, and an exercise program, along with patient reassurance, will adequately treat the majority of claudicators. When ischemia is present, patient education regarding foot care and avoidance of trauma are beneficial. Limb-threatening ischemia often requires revascularization. Adequate preoperative cardiologic evaluation and intraoperative monitoring have greatly reduced the morbidity and mortality of arterial reconstruction. Selection of the appropriate recipient vessel and bypass conduit enables limb salvage, whereas amputation would have been performed just a few years ago. Continued analysis of treatment outcomes will further define appropriate intervention in the future. PMID- 1735065 TI - Peripheral vascular surgery. AB - Patients may present with a wide range of manifestations of arterial occlusive disease. The clinician must be able to assess the magnitude of the arterial flow diminution and thereby determine the appropriate treatment regimen. A careful history, physical examination, and pertinent noninvasive vascular laboratory tests should provide adequate information for the clinician to establish the severity of disease and the need to pursue a medical or surgical treatment plan. Patient evaluation must be carried out expeditiously, especially when limb threatening conditions such as infection or gangrene exist, because these problems may progress rapidly and result in major lower extremity amputation. PMID- 1735066 TI - Venous diseases. AB - Deep venous thrombosis and its sequelae, pulmonary embolism, recurrence, and the postthrombotic syndrome, affects a staggering number of patients. Deep venous thrombosis is a frequent postoperative complication, especially after certain orthopedic operations. Pulmonary embolism is the third leading cause of death in the United States, and the postthrombotic syndrome effects an estimated 500,000 Americans. Prompt diagnosis and treatment of thromboembolic disease is important, but prevention may be the key to lessening the number of patients with venous disease in the future. PMID- 1735067 TI - Hispanic patients with head and neck cancer do not have a worse prognosis than Anglo-American patients. AB - This study was undertaken to determine whether the survival of Hispanic patients with squamous cell carcinoma of the head and neck was different from that of Anglo-American patients. The charts of 275 male patients with a diagnosis of squamous cell carcinoma of the head and neck at one Veterans Administration Hospital were reviewed in an attempt to identify prognostic indicators for both ethnic groups. No differences were observed between Anglo-American and Hispanic patients with respect to sites of the primary tumor, age at diagnosis, performance status, or the frequency of surgery, radiation therapy, or chemotherapy; however, there was a tendency for Hispanic patients to have received more treatment. There also was a trend (P = 0.12) for Hispanic patients to have a more advanced stage of cancer. Hispanic patients lost significantly more weight (P less than 0.001) and had significantly lower serum albumin levels (P less than 0.0001). According to the results of multivariate survival analyses, the variables that were predictive of a poor prognosis included advanced stage of disease, decreased serum albumin levels, increased weight loss, administration of chemotherapy, lack of radiation therapy or surgery, and advanced age. Ethnicity was not a significant predictor of survival either in univariate analyses, or within patients with the same stage of disease, or after adjustment for other prognostic factors. In conclusion, the natural history of squamous cell carcinoma of the head and neck is the same for Hispanic and Anglo-American patients. PMID- 1735068 TI - A phase II study of piritrexim in patients with advanced squamous head and neck cancer. AB - Piritrexim (PTX) is a newly developed lipid-soluble folate antagonist that crosses the cell membrane by a simple, rapid, carrier-independent diffusion process. A Phase II study was conducted to evaluate the activity of PTX in 34 patients with previously chemotherapy-naive squamous cell cancer of the head and neck area (SCCHN). Among them, 30 patients had received previous radiation therapy and/or surgery. Of 33 patients who could be examined, 3 had a complete response (CR), 6 had a partial response (PR), 11 had no change, and 13 had disease progression. The overall response rate (CR + PR) was 27% (9 of 33; 95% confidence interval, 13% to 46%). The response duration ranged from 36 to 360 + days (median, 162) and was similar to the best studies reported with methotrexate. The three most severe side effects (Grades 3 and 4 by World Health Organization criteria) were leukopenia, thrombocytopenia, and mucositis. These occurred in 41%, 26%, and 15% of the 34 patients, respectively. This study established PTX as an agent with some activity in SCCHN. The use of PTX in combination chemotherapeutic regimens needs to be explored. PMID- 1735069 TI - Mouse rosettes and surface immunoglobulin in small lymphocytic lymphoma. Importance in immunophenotyping and differential diagnosis. AB - Cell suspensions from lymphoid tissue of 82 small lymphocytic lymphoma (SLL), 8 intermediate lymphocytic lymphoma (ILL), 286 other B-non-Hodgkin's lymphoma (B NHL), and 248 reactive lymphadenopathy (RLA) cases were analyzed to evaluate the diagnostic significance of mouse-rosette (M-rosette) assay, and surface immunoglobulin clonality (SIg) and level of expression. In SLL, 55 were M-rosette positive (67.07%) and 72 SIg positive (87.8%), with weak fluorescence in 63 and strong fluorescence in 9 cases. Of 10 SIg-negative cases, 9 were M-rosette positive; of 27 M-rosette-negative cases, 26 were SIg positive. Seven of the nine cases with strong fluorescence were M-rosette positive. In other B-NHL, 252 were M-rosette negative (88.11%) and 245 SIg positive (85.66%), with strong fluorescence in 211 and weak fluorescence in 34 cases. Thirty-two of the 34 cases with weak fluorescence were M-rosette negative. Of the RLA cases, 213 were M rosette negative (85.89%) and 1 SIg positive (0.4%). The study demonstrated the independent expression of M-rosettes and SIg in SLL and their complementary role in diagnosis. It showed that positive results for M-rosettes and weak fluorescence are characteristic of SLL, that M-rosette negativity and strong fluorescence are characteristic of other B-NHL, and that M-rosette negativity and polyclonal SIg are characteristic of RLA. In 26 cases with paired data for CD5, M rosettes, and SIg, a positive result for M-rosettes was superior to CD5 in differentiating SLL from other B-NHL. Intermediate lymphocytic lymphoma frequently showed weak SIg fluorescence and M-rosette negativity. PMID- 1735070 TI - Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin. AB - A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha-naphthyl butyrate esterase, and periodic acid-Schiff stains. HD-70 cells are positive for CD30 (Ki 1/Ber-H2), CD15 (Leu-M1), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T-cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotransplantation of the HD-70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD-70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkin's disease. PMID- 1735071 TI - The prognostic significance of total serum cholesterol in patients with Hodgkin's disease. AB - In the current retrospective study, the authors investigated the prognostic significance of total serum cholesterol values at the time of diagnosis in patients with Hodgkin's disease (n = 179). Cholesterol values were significantly lower in these patients than in age- and sex-matched controls. Subgroups with advanced stages (P less than or equal to 0.01), poor response to therapy (P = 0.04), and relapse after complete response (P = 0.026) (but not with bulky disease) had lower cholesterol values. By univariate analysis (cut-point value, 140 mg/dl), the 5-year survival rate was 2.5 times higher in patients with normal cholesterol values than in hypocholesterolemic patients (P less than 0.00009). Hypocholesterolemia was retained as an adverse, independent prognostic factor by multivariate Cox regression analysis. The authors concluded that total serum cholesterol values at the time of diagnosis may be a parameter with unrecognized significance in Hodgkin's disease. PMID- 1735072 TI - Hodgkin's disease in Kenya. AB - A total of 136 patients with Hodgkin's disease (HD) seen at a national referral hospital in Kenya over a 15-year period were studied. The overall male-to-female ratio was 2.6:1, with 65% of patients younger than 20 years of age. The bimodal incidence of HD frequently seen in the developed nations was absent, and the histologic pattern of the disease was similar to that seen in other African countries. Fifty percent of patients had advanced-stage disease when first seen. Over two thirds of patients treated had a clinical remission, and the relapse rate in all stages was approximately 30%. Therapy-related complications were common, with frequent myelosuppression and younger patients more susceptible. PMID- 1735073 TI - Neuraxis dissemination in pediatric brain tumors. Response to preirradiation chemotherapy. AB - Of 29 consecutive children treated for malignant primary tumors of the central nervous system (CNS) at this institution, postoperative examination showed radiographic or cytologic evidence of neuraxis dissemination in 10 (34%). Given the historically poor results in disseminated CNS tumors treated with surgery and radiation therapy alone, these ten patients were treated prospectively with an investigational Phase II protocol consisting of preirradiation cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 3 and 4). The diagnoses included medulloblastoma (n = 4), malignant glioma (n = 3), cerebral primitive neuroectodermal tumor (n = 1), pineoblastoma (n = 1), and mixed glioma of the brainstem (n = 1). Postoperative neuraxis scanning with computed tomography, magnetic resonance imaging, or spinal myelography showed measurable intracranial or spinal metastases in all children. The cerebrospinal fluid (CSF) cytologic examination was positive for tumor cells in five. The best responses, based on serial imaging of neuraxis metastases, included two complete responses, four partial responses, and three stable disease states. One patient had progressive disease at the primary site despite stable disease in the spine; progressive neuraxis disease was documented in only one patient during chemotherapy. Clearance of tumor cells from the CSF was documented in three patients. The adverse effects of chemotherapy, consisting of transient myelosuppression and mild ototoxicity, were minimal. Reversible neurologic deterioration occurred in two patients; one patient became acutely quadriplegic after a prolonged convulsive seizure without radiographic evidence of tumor progression. PMID- 1735074 TI - Patients with cancer and their spouse caregivers. Perceptions of the illness experience. AB - This study focuses on patterns of response between patients with cancer and their spouse caregivers to examine the reliability of spouse informants in research and clinical settings. Thirty dyads (patient with cancer-spouse caregiver couples; total n = 60) were interviewed concurrently in their homes concerning patient functioning, psychologic distress, physical symptoms, caregiver perceptions of patient functioning, and marriage quality. Couples had been married an average of 32 years. Patients had either the lung or colon as their primary cancer site, and one third had metastasis. Correlations between 14 variable pairs and cross tabulation of scale scores suggest that spouse caregivers agree with patients on objective measures with observable referents (e.g., ability to dress independently). Partners disagree on subjective aspects of patient functioning (e.g., depression, fear of future, and confidence in treatment) and marriage quality. Almost without exception, caregivers viewed patients' functioning more negatively than patients described themselves. Patients, however, viewed marital quality more negatively than did caregivers. It was concluded that caregivers can serve as proxies for patients with cancer in research and clinical settings when objective data are sought. Data from both spouses are needed, however, to complete the picture of subjective illness experiences in patients with cancer, including perceptions of pain and disease symptoms. PMID- 1735075 TI - Pharmacokinetic and pharmacodynamic studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma. AB - The pharmacokinetics and pharmacodynamics of mitoxantrone were studied in 15 patients with advanced nasopharyngeal carcinoma (NPC) after single intravenous rapid infusion (12 to 14 mg/m2). Mitoxantrone plasma concentrations and urinary excretion were measured specifically with the use of a high-performance liquid chromatographic method with ultraviolet detection at 242 and 658 nm. The pharmacokinetic parameters are described adequately by a three-compartment model with a terminal half-life of 71.5 +/- 40.1 hours and a volume of distribution of 5037 +/- 2377 l. The total plasma clearance was 743 +/- 462 ml/minute, and the renal clearance was 18.8 +/- 8.49 ml/minute. Within 72 hours, 1.8 +/- 0.6% of the administration dose was excreted in urine as mitoxantrone parent compound. From the urinary excretion rate data, glomerular filtration and possible tubular reabsorption were the mechanisms involved in the urinary excretion of mitoxantrone. The values for unbound fraction (%) in plasma at time 0 and 5 minutes were 2.88 +/- 0.91% and 3.25 +/- 1.19%, with an average of 3.04 +/- 1.01%. The degree of protein binding of mitoxantrone was not affected by concentration (P greater than 0.05) in Chinese patients with NPC. The response rate for mitoxantrone was poor in this study. Clinical studies have demonstrated that mitoxantrone was generally well tolerated. Only very low incidences of nausea, vomiting, and alopecia were observed. The mild and rapidly reversible dose-limiting hematologic toxic effects have proven leukopenia. Although the toxicities reported here were tolerated for most patients, other combination regimens including mitoxantrone or other administration routes may be considered and need to be evaluated carefully. PMID- 1735076 TI - Extent of nasopharyngeal carcinoma involvement inside the nasopharynx. Lack of prognostic value on local control. AB - A study on the use of fiberscopic examination and multiple biopsy specimens taken from the nasopharynx in the assessment of the extent of nasopharyngeal carcinoma (NPC) involvement inside the nasopharynx found that the involvement often was more extensive than the detected with conventional methods. In the current study, 247 patients with NPC were studied with the use of fiberscopic examination, and multiple biopsy specimens were taken from the superior wall, posterior wall, and lateral wall of the nasopharynx on both sides. It was confirmed that the tumor often involved the nasopharynx extensively. Also, the extent of primary tumor involvement inside the nasopharynx was correlated with the American Joint Committee (AJC) T stage and the degree of paranasopharyngeal extension of the tumor (P = 0.0100 and 0.0009, respectively), as well as with the size of the largest node and the lowest neck level involved by the node in the ipsilateral neck (P = 0.0005 and 0.005, respectively). However, the extent of primary tumor involvement inside the nasopharynx, expressed as either the number of the six standard sites or the number of the AJC subsites that were involved, had no predictive value on the control of the primary tumor (P = 0.3773 and 0.7794, respectively) at a median follow-up time of 27 months. Except when salvage brachytherapy is contemplated for persistent or recurrent NPC, the extent of primary tumor involvement inside the nasopharynx should not be routinely studied. PMID- 1735077 TI - A case-control study of diet and social factors in cancer of the esophagus in Transkei. AB - A study of 100 patients with cancer of the esophagus and 100 controls matched for sex, age, and educational level was done in Transkei, with extensive inquiries into diet and social habits. The significant risk factors found were use of Solanum nigrum as a food (relative risk, 3.6), smoking (relative risk, 2.6), and use of traditional medicines (relative risk, 2.1). Consumption of traditional beer was not a risk factor. PMID- 1735078 TI - A phase II trial of 5-fluorouracil and recombinant alpha-2a-interferon in previously untreated metastatic gastric carcinoma. AB - A Phase II clinical trial of the combination of 5-fluorouracil (5-FU) and recombinant alpha-2a-interferon (alpha-2a-IFN) was conducted in 44 patients. Patients had not received chemotherapy previously and had measurable metastatic gastric carcinoma. 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/d for 5 consecutive days and as an intravenous bolus at a dose of 750 mg/m2 weekly for 7 weeks beginning on day 12. Recombinant alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) U three times a week during weeks 1 to 8. Patients were examined for response during week 9. Of 44 patients entered, 40 could be examined for response. Nine patients experienced a partial clinical response and one achieved a complete response, for an overall response rate of 25% (95% confidence interval, 13% to 41%). The median duration of response was 13 weeks (range, 9 to 67 weeks) and the median survival time was 29 weeks. Grade 3 to 4 toxicities included granulocytopenia (nine patients), diarrhea (three patients), oral mucositis (seven patients), skin rash (one patient), and fatigue (four patients). One patient died of neutropenic sepsis. This regimen had modest activity with significant toxicity and produced responses of short duration. It did not appear to be superior to existing treatments of metastatic gastric carcinoma. PMID- 1735079 TI - Adenoma--carcinoma sequence or "de novo" carcinogenesis? A study of adenomatous remnants in a population-based series of large bowel cancers. AB - Although it is well known that colorectal cancers can arise on a preexisting adenoma or de novo, the relative importance of these two pathways is still highly controversial. The authors studied the proportion of cancers with adenomatous remnants in a nonselected population-based series of 1630 resected colorectal cancers, so that they could estimate by subsite the importance of the adenoma carcinoma sequence. Four factors appeared to be related independently to the presence of adenomatous tissue within cancers in a multiple logistic model: tumor extension, growth pattern, location, and size. It appeared that infiltrating and ulcero-infiltrating tumors, which represented 39.8% of all resected colorectal cancers, very rarely displayed adenomatous tissue (0.5%), whereas it was more common in fungating and ulcero-fungating cancers (25.8%; P less than 0.001). In these exophytic cancers, the presence of adenomatous tissue was related very closely to the tumor size and extension, and it was seen in as many as 83% of small cancers (less than 2 cm) limited to the mucosa or submucosa. Right colon cancer showed consistently fewer adenomatous remnants than left colon or rectal cancer. These figures suggest that there are roughly two types of colorectal cancers, one of the infiltrating or ulcero-infiltrating type, which usually would arise de novo and account for approximately 40% of all colorectal cancer cases, and the exophytic type, which would mainly follow an adenoma-carcinoma sequence, although some might be de novo cancers, in particular in the right colon. PMID- 1735080 TI - A phase I trial of 5-fluorouracil, folinic acid, and alpha-2a-interferon in patients with metastatic colorectal carcinoma. AB - The mechanisms of biochemical modulation of 5-fluorouracil (5-FU) cytotoxicity by folinic acid (FA) have been elucidated, and the clinical use of this combination has improved response rates and survival in patients with metastatic colorectal cancer. Recently, Phase II trials also showed potential synergism between alpha 2a-interferon (rHuIFN-alpha 2a) and 5-FU. Therefore, a Phase I trial of these three agents 5-FU, FA, and rHuIFN-alpha 2a was conducted in patients with metastatic colorectal cancer. The drugs were given over 5 days, with dose escalation of either rHuIFN-alpha 2a or 5-FU. Fifty-five eligible patients were treated at eight dosing levels. The maximal tolerated dose (MTD) was as follows: 5-FU 430 mg/m2/d intravenously (IV) on days 1 to 5, FA 200 mg/m2 IV on days 1 to 5, and rHuIFN-alpha 2a 4.0 x 10(6) U/m2/d subcutaneously on days 1 to 5. The dose limiting toxicities were mucositis and neutropenia. Objective responses were seen at most dosing levels, and overall 15 of 55 patients (27%; 95% confidence interval, 16% to 41%) responded (median duration, 6.5 months). A Phase II trial using the MTD is ongoing. PMID- 1735081 TI - A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. AB - A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy. PMID- 1735082 TI - An immunohistochemical study with an estrogen receptor-related protein (ER-D5) in human colorectal cancer. AB - The ER-D5 antigen is a protein associated with the estrogen receptor that is present only in estrogen receptor-positive tissues. To clarify the estrogen receptor in colon cancer, the localization of ER-D5 was studied immunohistochemically. Forty-three of 171 (25.1%) specimens of colon cancer showed reactivity for ER-D5. Reactivity was seen only in the cytoplasm. No reactivity was seen in cancer limited to the mucosa or in adenoma, but submucosal cancers showed a rate of positivity similar to cancers that involved lamina muscularis and beyond. Estradiol staining was done on serial sections from 56 specimens. There was a significant relationship between reactivity for estradiol and that for ER-D5. In the 15 specimens where both ER-D5 and estradiol were positive, the distribution of estradiol was similar to that of ER-D5. It was concluded that the immunohistochemical localization of ER-D5 indirectly shows that of the estrogen receptor in colorectal cancer tissues. PMID- 1735083 TI - A clinicopathologic study on neural invasion in cancer of the pancreatic head. AB - Thirty-four patients who had resection of cancer of the pancreatic head were examined clinicopathologically to elucidate neural invasion of cancer of the pancreatic head to the extrapancreatic nerve plexus. Invasion of cancer to the retropancreatic tissue (rp+) was observed in 29 (85%) of the 34 patients, and neural invasion to the extrapancreatic nerve plexus was observed in 21 (72%) of the 29 patients with rp+. The incidence of invasion to the second region of the nerve plexus of the pancreatic head was high (14 patients; 67%). The degree of the neural invasion tended to increase as the intrapancreatic neural invasion became more severe and lymph vessel invasion more marked. Based on these findings, en bloc resection of the retropancreatic tissue involving the nerve plexus and fat tissue is necessary in the surgical treatment of cancer of the pancreatic head. PMID- 1735084 TI - A prospective trial of early detection of pancreatic cancer by ultrasonographic examination combined with measurement of serum elastase 1. AB - The accuracy of ultrasonographic examination combined with measurement of elastase 1 levels for early detection of pancreatic cancer was evaluated prospectively. Abdominal ultrasonographic examination and measurement of serum elastase 1 levels were done within 2 weeks after the initial visit to the clinic in a total of 2098 patients older than 35 years of age with symptoms suggesting pancreatic disease. Those in which one or both of these examinations had abnormal results underwent additional tests such as endoscopic retrograde cholangiopancreatography and computed tomography. Of those with pancreatosonograms with abnormal results with or without abnormally high serum elastase 1 levels, 19 patients eventually were found to have pancreatic cancer. No patients with pancreatic cancer, a normal level of serum elastase 1, and a pancreatosonogram with normal results were found, but follow-up studies revealed one pancreatic cancer in 189 patients after technically unsatisfactory ultrasonographic examination. In 9 (45%) of the 20 cases detected in this study, the pancreatic cancers were resectable, and two (10%) were less than 2.0 cm in longest diameter. These findings indicate that this combined examination is useful for early detection of pancreatic cancer. However, no pancreatic cancer was found in patients with abnormally high serum elastase 1 levels without a pancreatosonogram with abnormal results. Moreover, a combination of ultrasonographic examination and measurement of the elastase 1 level did not raise the diagnostic accuracy over that of ultrasonographic examination alone. These findings indicate that ultrasonographic examination alone is useful in screening for early pancreatic cancer. PMID- 1735085 TI - Expression of MDR1 and glutathione S transferase-pi genes and chemosensitivities in human gastrointestinal cancer. AB - The relationship was analyzed between drug resistance and MDR1 (with MDR signifying multiple drug resistance) and glutathione S transferase-pi (GST-pi) gene expression in four stomach and four colon cancer cell lines. Northern blot analysis by pmdr1 probe showed that stomach cancer cell lines had no detectable level of MDR1 mRNA expression. By contrast, some levels of MDR1 mRNA expression were found in two colon cancer cell lines, indicating doxorubicin resistance. To examine the MDR1 mRNA in each cell level, in situ hybridization was used. It was found that all colon cell lines and two stomach cell lines had more silver grains per cell than KB cells (a human KB kidney epidermoid carcinoma cell line). However, the number of silver grains in each cell was heterogeneous in the colon and stomach cell lines. Low-level MDR1 mRNA expression could be detected even in cell lines without MDR1 mRNA expression by northern blot hybridization. These results suggest the possibility that all gastrointestinal cell lines can acquire multiple drug resistance. In addition, all examined gastrointestinal cell lines had high GST-pi mRNA expression. This GST-pi gene expression shows cisplatin resistance in the examined cell lines. Heterogeneity of GST-pi mRNA expression also was shown at the cellular level. PMID- 1735086 TI - A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors. AB - The clinicopathologic and immunohistochemical features in 120 cases of gastrointestinal stromal tumor (GIST) were reviewed. Excluding 24 cases of gastric schwannoma, 96 cases of GIST consisting of 62 benign tumors and 34 sarcoma (low grade, 17; high grade, 17), with 9 cases arising in the esophagus, 57 in the stomach, 28 in the small intestine, and 2 in the colon, were studied. All esophagus and colon tumors were benign and resembled a conventional leiomyoma histologically. However, the gastric and small intestine benign tumors mostly showed histologic features of cellular or epithelioid leiomyoma. Immunohistochemically, desmin caused a positive reaction in all esophagus and colon tumors, but only 26% of gastric and small intestine tumors. However, muscle specific actin (HHF35) caused a positive reaction in most GIST (92%). The 10-year survival rates of the patients with gastric sarcoma and those with intestinal sarcoma were 74% and 17%, respectively. These results showed that histologic and immunohistochemical features were distinctly different, depending on the location in the gastrointestinal tract; that most GIST, excluding schwannoma, had smooth muscle differentiation; and that sarcomas had a more favorable prognosis when they occurred in the stomach rather than the intestine. PMID- 1735087 TI - Familial microcephaly with normal intelligence in a patient with acute lymphoblastic leukemia. AB - The authors describe a family with two children with microcephaly and normal intelligence, in which acute lymphoblastic leukemia developed in one of the siblings. An autosomal recessive pattern of inheritance is suggested by the pedigree. This is consistent with the literature, which the authors reviewed. All of the patients have similar phenotypic features, with some demonstrating chromosomal instability. It is important to recognize this syndrome because of the increased risk of lymphoreticular malignancy. PMID- 1735088 TI - Frequency of eosinophilia in adult T-cell leukemia/lymphoma. AB - Cases of adult T-cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T-cell lymphoma (TL), and 19 with B-cell lymphoma (BL) was investigated. The incidence of eosinophilia (greater than or equal to 570/microliters) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/microliters. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia. PMID- 1735089 TI - Response of brain metastases from breast cancer to systemic chemotherapy. AB - In a prospective, nonrandomized study, the response of brain metastases (BM) from breast cancer to a standard systemic chemotherapy regimen was measured by clinical follow-up and serial computed tomography (CT) scans. Treatment consisted of 4-week courses of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in 20 patients or 3-week courses of cyclophosphamide, doxorubicin, and 5 fluorouracil (CAF) in 2 patients. Seven patients had previously received CMF or CAF as adjuvant treatment or for progressive systemic disease. Another seven patients had been previously treated for BM with the use of surgery and/or radiation therapy (RT). Based on the results of clinical follow-up and CT scan, a response that lasted at least 6 weeks was seen in 13 patients (59%; 95% confidence interval, 37% to 80%), including 4 of the 7 patients with recurrent BM. Objective tumor regression occurred after two courses of chemotherapy in 76% of the patients who could be examined and after six courses in 47%. The median duration of neurologic remission in the 13 patients was 30 weeks (range, 15 to 66 weeks). The median overall survival time was 25 weeks (range, 2 to 83 weeks). The response rate of systemic disease paralleled the neurologic response. When compared with a matched group of historical control subjects treated with RT alone, chemotherapy induced a higher rate of neurologic response and led to a longer survival time. These results warrant further studies on the use of chemotherapy in BM from breast cancer. PMID- 1735090 TI - Past pregnancy is associated with axillary node involvement in women with breast cancer. AB - In 186 women with breast cancer, there was a progressive increase in the proportion of axillary nodal involvement as the number of pregnancies increased from zero to two or more (P = 0.026). Logistic regression analysis demonstrated that this effect was independent of the known relationship of age and tumor size to nodal involvement. Race and history of breast feeding had no influence on nodal involvement. PMID- 1735091 TI - Tumor hormone receptor status and recurrences in premenopausal patients with node negative breast carcinoma. AB - To ascertain the prognostic significance of tumor hormone receptor status in premenopausal patients with node-negative breast cancer, a retrospective review of 199 patients who met these criteria was conducted. Of these 199 patients, estrogen receptor (ER) data were available for 147. One hundred four patients (71%) had ER-negative disease and 22 (21%) exhibited local or distant recurrence with a median follow-up time of 85.4 months. Thirteen patients in this group had died of breast cancer. Of the 43 patients who had ER-positive disease, 5 (12%) had recurrences and 2 died of breast cancer. After observing patients for a longer period of time (median follow-up time, 85.4 months), no statistically significant differences in disease-free survival (DFS) or overall survival (OS) were demonstrated. However, as seen in our first analysis of this group at 45 months, tumor size after a median follow-up time of 85.4 months continues to have significant prognostic implications, regardless of ER status. PMID- 1735093 TI - The hypnozoite and relapse in primate malaria. AB - Although the phenomenon of malarial relapse was known to the ancients, the mechanism has only recently been explained satisfactorily. The long-held hypothesis of a tissue "cycle" in primate malaria as a cause of relapse did not fit clinical and experimental observations. A latent stage for Plasmodium spp. in the liver, for which there is now extensive morphological and experimental confirmation, best explains both the relapse phenomenon and the long prepatent periods seen with some strains of Plasmodium vivax. These latent stages (hypnozoites) have been detected in three relapsing malarias and have been found to persist in the liver as uninucleate parasites for up to 229 days after sporozoite inoculation. They have been found in in vitro cultures of two species of Plasmodium, and their ultrastructure has been partially described. PMID- 1735092 TI - Agents of newly recognized or infrequently encountered mycobacterial diseases. AB - This paper reviews recent information on the systematics and clinical significance of potentially pathogenic environmental mycobacteria. A short history of these mycobacteria is given. Information on species for which clinical and systematic aspects have already been well documented, i.e., Mycobacterium kansasii, M. marinum, M. scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi, and members of the M. fortuitum complex, is updated. Although the M. avium complex was extensively reviewed in earlier literature, major new systematic and clinical information is presented in some detail. Species that have received very limited prior coverage, i.e., M. asiaticum, M. haemophilum, M. malmoense, and M. shimoidei, are the main subjects of this review and are discussed in detail. The rare infections attributed to species that are normally considered nonpathogenic, i.e., M. gastri, M. gordonae, the M. terrae complex, and most of the rapidly growing mycobacteria outside of the M. fortuitum complex, are critically reviewed. Finally, suggestions are offered for practical measures that can minimize the risk of failing to isolate or misidentifying some of the more obscure potentially pathogenic environmental mycobacteria that are only infrequently recognized. PMID- 1735094 TI - Microbiological aspects of peritonitis associated with continuous ambulatory peritoneal dialysis. AB - The process of continuous ambulatory peritoneal dialysis has provided a useful, relatively inexpensive, and safe alternative for patients with end-stage renal disease. Infectious peritonitis, however, has limited a more widespread acceptance of this technique. The definition of peritonitis in this patient population is not universally accepted and does not always include the laboratory support of a positive culture (or Gram stain). In part, the omission of clinical microbiological findings stems from the lack of sensitivity of earlier microbiological efforts. Peritonitis results from decreased host phagocytic efficiency with depressed phagocytosis and bactericidal capacity of peritoneal macrophages. During episodes of peritonitis, fluid movement is reversed, away from the lymphatics and peritoneal membrane and toward the cavity. As a result, bloodstream infections are rare. Most peritonitis episodes are caused by bacteria. Coagulase-negative staphylococci are the most frequently isolated organisms, usually originating from the skin flora, but a wide array of microbial species have been documented as agents of peritonitis. Clinical microbiology laboratories need to be cognizant of the diverse agents so that appropriate primary media can be used. The quantity of dialysate fluid that is prepared for culture is critical and should constitute at least 10 ml. The sensitivity of the cultural approach depends on the volume of dialysate, its pretreatment (lysis or centrifugation), the media used, and the mode of incubation. The low concentration of microorganisms in dialysate fluids accounts for negative Gram stain results. Prevention of infection in continuous ambulatory peritoneal dialysis patients is associated with the socioeconomic status of the patient, advances in equipment (catheter) technology, and, probably least important, the application of prophylactic antimicrobial agents. PMID- 1735096 TI - Autoimmunity in the age of molecular biology. PMID- 1735095 TI - Giardiasis. AB - Giardiasis is one of the most common pathogenic intestinal protozoal infections worldwide. Giardia lamblia is the most frequently identified etiologic agent in outbreaks associated with the ingestion of surface water, often due to ineffective filtration or pretreatment. In addition to humans, other sources of infection include beavers, perhaps muskrats, and possibly domestic animals. A low infecting dose (10 to 25 cysts) is reported to be sufficient to produce human infection. Clinical manifestations range from asymptomatic to a transient or persistent acute stage, with steatorrhea, intermittent diarrhea, and weight loss, or to a subacute or chronic stage that can mimic gallbladder or peptic ulcer disease. Diagnosis is usually based on repeated stool examinations but examination of duodenal fluid or biopsy material may also be necessary. Enzyme immunoassay or indirect immunofluorescence methods for direct detection of antigen or whole organisms in clinical specimens have also been developed. These tests are reported to be more sensitive than routine stool examination. Demonstration of serum immunoglobulin M and G antibodies may help differentiate recent from past infection or help detect recurrence in individuals who have been treated previously. Serum immunoglobulin A levels may be a useful indicator of exposure in waterborne outbreaks of diarrhea. Drugs available for treatment within the United States include metronidazole, quinacrine hydrochloride, and furazolidone. PMID- 1735097 TI - Clinical and molecular aspects of autoimmune diseases. PMID- 1735098 TI - Manipulation of anti-DNA idiotypes: a possible treatment approach to autoimmune diseases. PMID- 1735099 TI - Cytokines in autoimmune diseases. PMID- 1735100 TI - Sjogren's syndrome and autoimmunity. PMID- 1735101 TI - New approaches to the genetics of autoimmune disease. PMID- 1735102 TI - Clinical and molecular aspects of autoimmune endocrine disease. PMID- 1735103 TI - New approaches to the molecular analysis of the spondyloarthropathies. PMID- 1735104 TI - Immunopathogenesis of autoimmunity following human immunodeficiency virus infection. PMID- 1735105 TI - Molecular analysis of autoantibody production. PMID- 1735106 TI - Mechanisms of anti-DNA antibody expression in normal and aberrant immunity. PMID- 1735107 TI - Anti-DNA idiotypes: their pathogenic role in autoimmunity. PMID- 1735108 TI - Ultrastructural localization of sialylated glycoconjugates in cells of the salamander olfactory mucosa using lectin cytochemistry. AB - An indirect gold-labeling method utilizing the lectin from Limax flavus was employed to characterize the subcellular distribution of sialic acid in glycoconjugates of the salamander olfactory mucosa. The highest density of lectin binding sites was in secretory vesicles of sustentacular cells. Significantly lower densities of lectin binding sites were found in secretory granules of acinar cells of both Bowman's and respiratory glands. Lectin binding in acinar cells of Bowman's glands was confined primarily to electron-lucent regions and membranes of secretory granules. In the olfactory mucus, the density of lectin binding sites was greater in the region of mucus closest to the nasal cavity than in that closest to the epithelial surface. At the epithelial surface, the density of lectin binding sites associated with olfactory cilia was 2.4-fold greater than that associated with microvilli of sustentacular cells or non-ciliary plasma membranes of olfactory receptor neurons, and 7.9-fold greater than non microvillar sustentacular cell plasma membranes. Lectin binding sites were primarily associated with the glycocalyx of olfactory receptor cilia. The cilia on cells in the respiratory epithelium contained few lectin binding sites. Thus, sialylated glycoconjugates secreted by sustentacular cells are preferentially localized in the glycocalyx of the cilia of olfactory receptor neurons. PMID- 1735109 TI - Localization of basic fibroblast growth factor in a subpopulation of rat sensory neurons. AB - The distribution of basic fibroblast growth factor (bFGF)-immunoreactivity (IR) was studied in rat sensory and autonomic ganglia. In postnatal and adult sympathetic superior cervical ganglia and in adult parasympathetic otic ganglia no bFGF-staining was found. Postnatal and adult neural crest- and placode-derived sensory ganglia displayed intensive bFGF-IR in a neuronal subpopulation. This subpopulation was characterized by use of consecutive sections of adult dorsal root ganglia stained with antibodies against substance P, somatostatin, bombesin, and bFGF. Basic FGF was colocalized with the somatostatin/bombesin subpopulation but not with substance P. PMID- 1735110 TI - Significance of the peri-insular extracellular matrix for islet isolation from the pancreas of rat, dog, pig, and man. AB - The presence and distribution in the peri-insular region of extracellular matrix, and in particular basement membrane, was investigated in a comparative study comprising pancreata of rat, dog, pig, and man. Basement membrane markers, collagen type-IV and laminin, were determined immunohistochemically. Additional information pertaining to the structural relationships between endocrine and exocrine pancreas, in particular cell-to-cell and cell-to-matrix contacts, was obtained by electron microscopy. In pig, very little peri-insular capsule is present, and the structural integration of the porcine islet in the exocrine pancreas almost exclusively depends on cell-to-cell adhesion. In the canine pancreas, the islets are almost completely encapsulated with very little direct exocrine-to-endocrine cell-to-cell contact. In rat and man, the situation is intermediate with a tendency towards predominance of cell-to-matrix adhesion. The intra-insular adhesion mechanisms depend largely on cell-to-cell adhesion in all four species. The ultrastructural results suggest that collagenase preparations employed in islet isolation procedures should be of high purity as to preserve the protease-sensitive intra-islet cell-to-cell adhesion. Under these conditions, however, the endocrine-to-exocrine cell-to-cell contacts will be conserved also, resulting in an exocrine-tissue contamination of the islets of Langerhans. Consequently, additional steps for the effective removal of exocrine tissue and the purification of islets are required. PMID- 1735111 TI - The optic lobe of Drosophila melanogaster. II. Sorting of retinotopic pathways in the medulla. AB - We present a quantitative evaluation of Golgi-impregnated columnar neurons in the optic lobe of wild-type Drosophila melanogaster. This analysis reveals the overall connectivity pattern between the 10 neuropil layers of the medulla and demonstrates the existence of at least three major visual pathways. Pathway 1 connects medulla layer M10 to the lobula plate. Input layers of this pathway are M1 and M5. Pathway 2 connects M9 to shallow layers of the lobula, which in turn are tightly linked to the lobula plate. This pathway gets major input via M2. Pathways 1 and 2 receive input from retinula cells R1-6, either via the lamina monopolar cell L1 (terminating in M1 and M5) or via L2 and T1 (terminating in M2). Neurons of these pathways typically have small dendritic fields. We discuss evidence that pathways 1 and 2 may play a major role in motion detection. Pathway 3 connects M8 to deep layers of the lobula. In M8 information converges that is derived either from M3 (pathway 3a) or from M4 and M6 (pathway 3b), layers that get their major input from L3 and R8 or L4 and R7, respectively. Some neurons of pathway 3 have large dendritic fields. We suggest that they may be involved in the computation of form and colour. Possible analogies to the organization of pathways in the visual system of vertebrates are discussed. PMID- 1735112 TI - Local production of fibronectin by ectopic human retinal cells. AB - The distribution of fibronectin mRNA and fibronectin in adult human retina and epiretinal membranes was investigated by in situ hybridisation and immunohistochemical techniques. The cells in normal adult retina contained little or no fibronectin mRNA and the retina only showed fibronectin immunoreactivity in retinal vessels. The cells in detached neuroretina did not contain fibronectin message but the vitreoretinal interface of the detached retina exhibited variable fibronectin immunoreactivity. Retinal glia, retinal pigment epithelium and fibroblast-like cells in membranes at the vitreoretinal juncture (epiretinal membranes) showed variable labelling with the fibronectin mRNA probe and all the membranes immunostained for fibronectin. No difference could be detected between membrane cell types in the intensity of labelling with the mRNA probe or for fibronectin immunoreactivity. The results indicate that cells in situ in attached and detached adult human retina do not produce fibronectin. Although fibronectin at the vitreoretinal juncture in retinal detachment is probably partly derived from plasma fibronectin resulting from breakdown of the blood-retinal barrier, ectopic retinal cells produce fibronectin and contribute to the glycoprotein epiretinal membranes. PMID- 1735113 TI - Immunohistochemical localization of transthyretin in glomerular peripolar cells of newborn sheep. AB - Purified transthyretin has been isolated from sheep serum. Antiserum raised against this protein has been used with an indirect immunoperoxidase histochemical technique to identify transthyretin in newborn lamb kidney tissue. Transthyretin was found in proximal tubule cells and in glomerular peripolar cells. Preabsorption studies using purified transthyretin protein indicate that the immunoreactivity of the antiserum is specific to transthyretin. PMID- 1735114 TI - High frequency of ciliated neuropeptide Y-immunoreactive neurons in rat striatum. AB - An analysis of the ultrastructure of neuropeptide Y-immunoreactive neurons in rat striatum revealed the presence of a cilium in half of the neurons serially sectioned in part, and in a quarter of the neurons observed in single sections. It is speculated that the cilium is a developmental remnant, i.e., a sign of the less differentiated state of the NPY-containing neurons compared with the other neurons, and that this could explain the plasticity of this type of neuron after lesions. PMID- 1735115 TI - Calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses in the renal pelvis and ureter of rats. AB - The distribution of calcitonin gene-related peptide-immunoreactive nerve fibers in the renal pelvis and ureter was examined by immunohistochemistry using whole mount preparations and cryostat sections. The patterns of innervation were contrasted between the pelvis and ureter; the immunoreactive nerve fibers in the pelvis ran parallel to the long axis of each of the circular and longitudinal muscle layers, causing a lattice-like appearance of the nerve fibers. In the ureter, the immunoreactive fibers were accumulated in the subepithelial region and the longitudinal muscle. In both the pelvis and ureter, a portion of the nerve fibers of smaller caliber showed a swollen or beaded structure; they were located in the musculature and beneath the epithelium extending for considerable distances. Ligation of the ureter caused a marked decrease in the immunoreactive nerves in the pelvis and the proximal portion of the ureter, suggesting that the axonal flow in the calcitonin gene-related peptide-containing neurons of the ureter runs towards the pelvis. PMID- 1735116 TI - Immunohistochemical localization of Na(+)-dependent glucose transporter in rat jejunum. AB - Glucose is actively absorbed via a Na(+)-dependent active glucose transporter (Na GT) in the small intestine. We raised a polyclonal antibody against the peptide corresponding to amino acids 564-575 of rabbit intestinal Na-GT, and localized it immunohistochemically in the rat jejunum. By means of immunofluorescence staining, Na-GT was located at the brush border of the absorptive epithelial cells of the intestinal villi. Electron-microscopic examination showed that Na-GT was localized at the plasma membrane of the apical microvilli of these cells. Little Na-GT was found at the basolateral plasma membrane. Along the crypt-villus axis, all of the absorptive epithelial cells in the villus were positive for Na GT. In addition to the brush border staining, the supranuclear positive staining, which was shown to be the Golgi apparatus by use of electron microscopy, was seen in cells located between the base to the middle of the villus. Cells in crypts exhibited little or no staining for Na-GT. Goblet cells scattered in the intestinal epithelium were negative for Na-GT staining. These observations show that Na-GT is specific to the apical plasma membrane of the absorptive epithelial cells, and that the onset of Na-GT synthesis may occur near the crypt-villus junction. PMID- 1735117 TI - Salinity tolerance and structure of external and internal gills in tadpoles of the crab-eating frog, Rana cancrivora. AB - Salinity tolerance and histology of gills were studied in Rana cancrivora larvae. The tadpoles at the external gill stages (W stages 21-22) were able to survive in media containing up to 40% seawater, but died in water of higher salinity. Their external gills appear to have no critical role in adaptation to seawater. However, advanced tadpoles with internal gills (T-K stages I-XVIII) were able to tolerate 50% or higher seawater. In the internal gills, there are numerous mitochondria-rich cells (MR cells) scattered on the ventral and lateral epithelia of the gill arches and the gill tufts in both freshwater- and seawater-acclimated tadpoles. In freshwater-acclimated tadpoles there are three types of MR cell: (1) microplicated, (2) microvillous, and (3) apically vacuolated. In tadpoles acclimated to dilute seawater, the ratio of type-1 to type-2 cells is lower, although all three types of MR cell are present. In 60%-seawater-acclimated tadpoles, a few MR cells with a lumen and concave cytoplasm at the apical membrane (type 4) are present. The changes in MR cell morphology under ambient conditions of low or high salinity may reflect alterations in the physiological roles of the gills with regard to transport of ions. PMID- 1735118 TI - Receptor-mediated endocytosis of testicular transferrin by germinal cells of the rat testis. AB - The present study examines events of the Sertoli cell iron delivery pathway following the secretion of diferric testicular transferrin (tTf) into the adluminal compartment of the rat seminiferous epithelium. The unidirectional secretion of tTf by Sertoli cells was verified, in vivo, and it was shown that this protein is internalized by adluminal germ cells. It was further determined by Scatchard analysis that this internalization was mediated by high affinity transferrin binding sites on the surface of round spermatids, numbering 1453/cell and displaying a Kd = 0.6 x 10(-9) M. Northern blot analysis of RNA isolated from adluminal germ cells, namely spermatocytes, round spermatids and elongating spermatids, indicated that these cells expressed Tf receptor mRNA and ferritin mRNA in levels inversely related to their stage of maturation. Finally it was determined that following binding and internalization in round spermatids, Tf became associated with the endosomal compartment and was recycled back to the cell surface. This study illustrates the immediate fate of tTf once it is secreted by the Sertoli cells. Thus, diferric tTf binds of Tf receptor on the surface of adluminal germ cells, is internalized by receptor-mediated endocytosis and the apoTf-Tf receptor complex is recycled back to the cell surface where apotTf is released into the adluminal fluid. PMID- 1735119 TI - The presence and distribution of Antho-RFamide-like material in scyphomedusae. AB - The nervous systems of the scyphomedusae Chrysaora hysoscella, Cyanea capillata and Cyanea lamarckii (Phylum Cnidaria) were stained using an anti-serum against the anthozoan neuropeptide Antho-RFamide. Staining was widespread in all three species. In Chrysaora, the antiserum revealed nerve nets in the subumbrella and exumbrella ectoderm, in both faces of the oral lobes, and in the endoderm lining the subumbrella and exumbrella surfaces of the gastric cavity. The most prominent staining occurred in a dense plexus of neurons in the ectoderm at the base of the tentacles. This nerve net sent projections into the subumbrella ectoderm. For the most part, staining in the two species of Cyanea was similar to that in Chrysaora, with a few exceptions. These include the presence, in Cyanea, of an obvious tentacular nerve tract and nerve nets associated with clusters of cnidocytes in the tentacles. Radioimmunoassays of extracts from Chrysaora and Cyanea lamarkii revealed that both species contain large amounts of Antho-RFamide like material (up to 55 nmol/animal). The results indicate that Antho-RFamide like neuropeptides are widespread in scyphomedusae. PMID- 1735120 TI - Degeneration of osteoblasts involved in intramembranous ossification of fetal rat calvaria. AB - Ossification of calvariae from day-21 rat fetuses was reinvestigated by electron microscopy using different fixation techniques (glutaraldehyde/OsO4, tannic acid, ruthenium red, K-pyroantimonate). An osteoid layer with scattered mineral deposits was found at the mineralization front. Directly beyond this layer, a sheet of one to two layers of necrotic and degenerating osteoblasts was present. Above this sheet, normal and healthy cells were seen, formed by six to eight layers of flattened cells, embedded in a collagenous matrix. The osteoblasts on the less mineralizing opposite side of the calcified calvariae and the osteocytes embedded in the calcified calvariae appeared healthy. Closer inspection of the necrotic zone revealed apatite crystals in vesicles which most probably originated from mitochondria of the degenerated cells. Large K-pyroantimonate deposits were found throughout the osteoid and the necrotic zone, whereas only small granules were scattered in the cytoplasm and at the plasma membrane of the healthy cells directly adjacent to the necrotic zone. A concept of intramembranous mineralization is outlined, according to which osteoblasts store enormous amounts of calcium, which are liberated by physiological cell death in the vicinity of the mineralizing front. PMID- 1735121 TI - An identified dorsal unpaired median neurone and bilaterally projecting neurones exhibiting bovine pancreatic polypeptide-like/FMRFamide-like immunoreactivity in abdominal ganglia of the migratory locust. AB - Three antisera were used to study the distribution and anatomy of bovine pancreatic polypeptide (BPP)-like/FMRFamide-like immunoreactive neurones within the unfused abdominal ganglia of the migratory locust, Locusta migratoria. All the antisera used stained two or more clusters of perikarya, localized anteriorly and posteriorly near the midline within each unfused abdominal ganglion. Double labelling experiments with intracellular dye injection, or differential backfilling, combined with subsequent immunostaining were carried out to identify these neurones. Two of the antisera (antisera 1 and 2, both raised against FMRFamide) stained three groups of midline neurones, located anterior dorsal, anterior ventral and posterior dorsal within the ganglion. Neurones of the former of these two clusters projected via the anterior median nerve to a neurohaemal organ. The posterior cluster of midline cells comprised immunopositive perikarya all but one of which also projected via the anterior median nerve to innervate the neurohaemal organ. Double labelling with Lucifer yellow and antisera 1 and 2 showed that the remaining neurone was the previously identified dorsal unpaired median (DUM)heart 1 neurone. The third antiserum (AK141), also raised against FMRFamide, stained neurones within an anterior dorsal cluster, and in a posterior cluster. Double labelling with differential Co2+/Ni(2+)-backfilling and the antiserum 3 (AK141) demonstrated that the large neurones of both clusters belonged to the population of bilaterally projecting neurones (BPNs), including the DUMheart1 neurone. Since the antisera cross-react with BPP and fail to label neurones when preadsorped with BPP or FMRFamide, we conclude that the labelled neurones contain polypeptides of the FMRFamide/BPP-family. PMID- 1735123 TI - Physical and biochemical characterization of the cloned LYS5 gene required for alpha-aminoadipate reductase activity in the lysine biosynthetic pathway of Saccharomyces cerevisiae. AB - The LYS5 and LYS2 genes of Saccharomyces cerevisiae are required for the synthesis of alpha-aminoadipate reductase in the lysine pathway. The LYS5 gene, originally cloned as a DNA insert of the plasmid pSC5, has been subcloned on a 3.2 kb SphI-Sau3AI DNA fragment of the recombinant plasmid pSR7. An internal 2.1 kb HpaI-HpaI DNA fragment of the subclone, upon Southern hybridization, exhibits homology with HpaI-restricted wild-type S. cerevisiae genomic DNA. The lys5+ transformants exhibited alpha-aminoadipate reductase activity similar to that of wild-type cells. S1 nuclease analysis localizes the transcription initiation site relative to the detailed restriction map, and reveals the direction of transcription, as well as the transcript size of the LYS5 gene which can be no greater than 1.65 kb. From this it is estimated that the encoded polypeptide is appreciably smaller than the 4 kb LYS2 gene product. These results provide a physical and biochemical characterization of the cloned LYS5 gene. Based on these observations, it is concluded that the LYS5 gene encodes a relatively small polypeptide of the large heteropolymeric alpha-aminoadipate reductase. PMID- 1735122 TI - Gene database for the fission yeast Schizosaccharomyces pombe. AB - As an aid to the fission yeast genome project, we describe a database for Schizosaccharomyces pombe consisting of both genetic and physical information. As presented, it is therefore both an updated gene list of all the nuclear genes of the fission yeast, and provides an estimate of the physical distance between two mapped genes. Additionally, a field indicates whether the sequence of the gene is available. Currently, sequence information is available for 135 of the 501 known genes. PMID- 1735124 TI - A mating deficient and temperature-sensitive lethal mutant of Schizosaccharomyces pombe defines a new fertility locus. AB - A recessive mutant allele, mef1-84, of a novel locus mapping on the left arm of chromosome I, between ade3 and ura1, 5 cM apart from lys5, confers temperature sensitive growth and mating deficiency at the non-restrictive temperatures for growth. Two other mutations suppress the phenotype conferred by mef1-84: sts1-1 suppresses the temperature-sensitive growth only, and smd1-35 suppresses both temperature-sensitive growth and mating deficiency. PMID- 1735125 TI - Transcript analysis of penicillin genes from Penicillium chrysogenum. AB - The presence of a transcriptional control simultaneously affecting the expression of the three penicillin biosynthetic genes, pcbAB, pcbC, and penDE (pen genes), was demonstrated in Penicillium chrysogenum. Using probes specific to each gene, it was observed that the highest level of expression of the pen genes occurred during exponential growth, in both the original ancestral strain (NRRL1951) and a high-penicillin producing strain P2. Expression also occurred in the presence of high concentrations of glucose, indicating that carbon catabolite repression was not directly involved in the regulation. Transcription of the pen genes appeared to cease as the growth rate decreased. Growth was limited in a fermenter by the rate of oxygen transfer. The phosphoglycerate kinase gene (pgk), used as a control, was strongly induced by the reduced oxygen levels, suggesting a stress related response. By maintaining optimum growth conditions in fermenters, no induction of the pgk gene was observed whereas expression of the pen genes could be maintained. It was also possible to re-establish expression of the pen genes, after normal cessation, by the addition of cycloheximide to the culture medium. PMID- 1735126 TI - Cloning and expression of a chitinase gene from the hyperparasitic fungus Aphanocladium album. AB - Recombinant clones from a cDNA library of an Aphanocladium album chitinase overproducing mutant strain were isolated by screening with antiserum against a 39 kDa chitinase purified from this hyperparasitic fungus. Analysis of the isolated positive clones indicated that most of them carried the same cDNA. A cDNA from this group was used as a hybridization probe to isolate an 8 kb DNA fragment from a genomic library of the wild-type strain. The chitinase 1 gene was mapped to this fragment by two independent approaches. Its partial DNA sequence was in perfect agreement with an amino-terminal peptide sequence obtained by sequencing 23 amino acids of the 39 kDa chitinase. Its transfer in Fusarium oxysporum resulted in a transformant producing both a protein of about 39 kDa that cross-reacted with the chitinase antiserum and a chitinase activity that was inhibited by the same antiserum. Northern blot analysis indicates that the cloned chitinase gene was subject to catabolite repression and appeared inducible by chitin. PMID- 1735127 TI - Plastid DNA from Pyrenomonas salina (Cryptophyceae): physical map, genes, and evolutionary implications. AB - Cryptomonads are thought to have arisen from a symbiotic association between a eukaryotic flagellated host and a eukaryotic algal symbiont, presumably related to red algae. As organellar DNAs have proven to be useful tools in elucidating phylogenetic relationships, the plastid (pt) DNA of the cryptomonad alga Pyrenomonas salina has been characterized in some detail. A restriction map of the circular 127 kb ptDNA from Pyrenomonas salina was established. An inverted repeat (IR) region of about 5 kb separates two single-copy regions of 15 and 102 kb, respectively. It contains the genes for the small and large subunit of rRNA. Ten protein genes, coding for the large subunit of ribulose-1,5-bisphosphate carboxylase, the 47 kDa, 43 kDa and 32 kDa proteins of photosystem II, the ribosomal proteins L2, S7 and S11, the elongation factor Tu, as well as the alpha and beta-subunits of ATP synthase, have been localized on the restriction map either by hybridization of heterologous gene probes or by sequence homologies. The gene for the plastidal small subunit (SSUr) RNA has been sequenced and compared to homologous SSU regions from the cyanobacterium Anacystis nidulans and plastids from rhodophytes, chromophytes, euglenoids, chlorophytes, and land plants. A phylogenetic tree constructed with the neighborliness method and indicating a relationship of cryptomonad plastids with those of red algae is presented. PMID- 1735128 TI - One-step transformation of yeast in stationary phase. AB - A fast yeast-transformation technique has been developed by adding thio compounds to alkali-ion based protocols and incubating at 45 degrees C. This procedure is especially recommended for cells from stationary phase at a density up to 2.5 x 10(8) cells/ml. It involves only one step for the preparation and transformation of competent cells within 30 min. The yield was more than 10(4) transformants/microgram plasmid DNA. This protocol is easy to scale up for many DNA samples and is also applicable for yeast cells from different types of storages. PMID- 1735129 TI - The DNA repair gene PSO3 of Saccharomyces cerevisiae belongs to the RAD3 epistasis group. AB - The mutant allele pso3-1 of Saccharomyces cerevisiae confers sensitivity to treatment with UV365nm (UVA) light-activated mono- and bi-functional psoralens. When pso3-1 is combined in double mutants with selected rad and pso mutant alleles and subjected to 8-MOP + UVA treatment, epistatic interaction with regard to survival is observed with pso1, pso2, and rad3. With the same treatment the combination of pso3-1 with rad6 and rad52 leads to synergistic interaction. For the monofunctional agent 3-carbethoxypsoralen (3-CPs) the analysis of double mutants yields the same results as with the bifunctional 8-methoxypsoralen (8 MOP) with the exception of the pso1-1pso3-1 double mutant. Here we find an additive interaction, i.e., the sensitivities of both parental strains are summed in the double mutant, which indicates a different substrate specificity of the repair activity encoded by the PSO1 and PSO3 genes. PMID- 1735130 TI - Differential muscarinic receptor mRNA expression by freshly isolated and cultured bovine aortic endothelial cells. AB - Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be related to changes in muscarinic receptor expression. Northern blot analysis of poly(A) + RNA from freshly isolated or cultured bovine aortic endothelial cells was used to address this problem. Through the use of specific cDNA probes complementary to the nonconserved regions of the m1, m2, m3, m4, and m5 muscarinic receptors, mRNA transcripts for the m1 (3.9 kb), m2 (3.8 kb), and m3 (3.1 kb) receptor subtypes were identified in freshly isolated endothelial cells, whereas m1 and m3 transcripts were identified in aortic smooth muscle. In contrast, cultured endothelial cells contained mRNA for only the m2 receptor subtype. Transcripts for the m4 or m5 receptors were not detected in either freshly isolated or cultured endothelial cells. Since m1 and m3 receptor subtypes are coupled to phospholipase C, activation of which is required for EDRF release, these observations may explain the failure of muscarinic agonists to elicit a rise in [Ca2+]i and EDRF release from cultured endothelial cells. PMID- 1735131 TI - Effect of temperature change on the permeability of eel rete capillaries. AB - The changes in the permeability properties of the rete capillaries of the eel in response to temperature shifts were studied during countercurrent perfusion at constant flow and pressure. Tracers and oxygen were added to the arterial perfusate. From the ratio of end concentrations of arterial to venous capillaries divided by surface area, calculated from rete weight, a value for the ratio of permeability to flow, P/F, with dimensions in centimeters-2 was estimated. Because flow and surface area are constant, this provides an index of how permeability varies with time. A group of paracellular (albumin, sucrose, and sodium) and cellular (antipyrine, water, and oxygen) probes were used. When the temperature of the perfusate was raised abruptly from 25 degrees C to 35 degrees C, P/F values rose continuously and irreversibly from 0.042 +/- 0.009 to 0.281 +/ 0.112 cm-2 (mean +/- SEM) for 125I-albumin, from 0.082 +/- 0.006 to 1.74 +/- 0.070 cm-2 for [14C]sucrose, and from 0.32 +/- 0.06 to 2.78 +/- 0.62 cm-2 for 22Na, whereas they were not modified for [14C]antipyrine, [3H]water, and O2. Gradual increase of temperature was accompanied by a smaller rise in sucrose and sodium permeability and no change in albumin permeability; with decrease, the change was reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735132 TI - JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells. AB - The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE. PMID- 1735133 TI - Effect of a cigarette smoke extract on the metabolism of the proinflammatory autacoid, platelet-activating factor. AB - Cigarette smoking is associated with an increased incidence of a number of diseases. Minimal information is available at the molecular level concerning the mechanism of action of cigarette smoke. Platelet-activating factor (PAF) is one of the most potent proinflammatory agents described. PAF concentration may be regulated by the degradation of PAF as catalyzed by the plasma enzyme, PAF acetylhydrolase (PAF-AH). This enzyme is associated with the lipoprotein fraction. The exposure of low density lipoprotein to a cigarette smoke extract (CSE) has been shown to alter the charge of low density lipoprotein and its uptake by macrophages. The activity of PAF-AH in the lipoprotein fraction has been assayed after exposure to CSE. The activity of PAF-AH was inhibited by the CSE in a dose-dependent manner. The inhibition of PAF-AH by the CSE was not altered by superoxide dismutase or catalase addition. Sulfhydryl compounds prevented and reversed the inhibition of PAF-AH caused by CSE. The inhibitor present in CSE was not nicotine, its major metabolic product, (-)-cotinine, or several compounds known to be present in the extract. The charge alteration reaction(s) and PAF-AH inhibition appear to be localized at different sites of the lipoprotein molecule. The observed inhibition may account for the increase in the plasma PAF concentration that is known to occur in smokers. The increase of PAF may contribute to the increased incidence of cardiovascular and lung diseases known to be present in smokers. PMID- 1735134 TI - Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro. AB - Intravascular stents, currently in experimental human use for recurrent arterial stenosis, are plagued by subacute thrombosis. As a therapeutic approach to stent related thrombosis, we and others have suggested coating stents with endothelial cells before implantation. In a previous study we demonstrated the feasibility of coating stents with endothelial cells that were genetically modified to secrete large amounts of human tissue plasminogen activator. In the present study we attempted both to develop a clinically applicable protocol for stent seeding and to test whether seeded cells would remain adherent to stents after exposure to pulsatile flow. Endothelial cells were harvested from the saphenous veins of sheep with survival of the donor animals. Harvested cells were transduced with a retroviral vector containing a marker gene and seeded onto catheter-mounted stents under sterile conditions. Scanning electron microscopy revealed complete coverage of the stent surfaces by seeded cells. Stents were expanded and exposed to pulsatile flow in vitro. Substantial cell retention was observed on the lateral stent surfaces by light microscopy and scanning electron microscopy; fewer cells were seen on the luminal and abluminal surfaces. Removal of seeded cells from flow-exposed stents by trypsin digestion resulted in the recovery of approximately 70% of the seeded cells. These cells were viable and healthy as judged by their ability to proliferate to confluence with the same kinetics as control (non-flow-exposed) cells. Autologous genetically modified endothelial cells can be seeded onto catheter-mounted stents in a sterile manner, and stent deployment under flow conditions results in substantial retention of viable cells. PMID- 1735135 TI - Influence of platelet-vessel wall interactions on leukocyte rolling in vivo. AB - The influence of platelet-vessel wall interactions on leukocyte rolling was investigated in rabbit mesenteric venules (diameter, 21-40 microns) using intravital videomicroscopy. Puncture of the wall with glass micropipettes (tip, 6 8 microns) evoked the formation of a thrombus in all venules. In most vessels, emboli were produced as well. The rolling of leukocytes (i.e., their movement along the vessel wall at a velocity clearly lower than that of the other blood cells) was quantitated simultaneously in vessel segments upstream and downstream from a thrombus up to 10 minutes after puncture. During embolization the number of rolling leukocytes decreased significantly from the upstream to the downstream vessel segment (median decrease, 45%; p less than or equal to 0.001). It was still decreased by approximately 50% after embolization had stopped, indicating that the decrease in leukocyte rolling was not caused by inclusion of leukocytes in the emboli. In venules without embolization, leukocyte rolling did not change systematically, indicating that fluid dynamic changes induced by the thrombus do not influence leukocyte rolling. Inhibition of prostaglandin formation with aspirin (100 mg/kg) almost completely abolished the influence of the thromboembolic reaction on leukocyte rolling, but blockade of thromboxane A2 receptors with sulotroban (30 mg/kg) had no effect. In conclusion, this is the first report on a functional interaction in vivo, at a site of vessel wall injury, between platelets, vascular cells, and leukocytes. The findings suggest that substances produced by activated platelets and/or damaged vascular cells diminish leukocyte rolling. The identity of these substances is not yet clear, but the present study indicates that prostaglandins other than thromboxane A2 are involved. PMID- 1735136 TI - Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L arginine methyl ester in the cat. AB - The effect of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor production, on the vasodilator response to efferent vagal stimulation was investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was increased with U46619, efferent vagal stimulation decreased lobar arterial pressure in a stimulus-frequency dependent manner. The decreases in lobar arterial pressure were enhanced by pretreatment with reserpine, were blocked by atropine, and were not altered by propranolol, indicating that the neurogenic vasodilator response was cholinergic in nature. The decreases in lobar arterial pressure in response to vagal stimulation and to exogenously administered acetylcholine were reduced after administration of L-NAME (100 mg/kg i.v.). Although L-NAME decreased pulmonary vasodilator responses to vagal stimulation and to acetylcholine, responses to adenosine, nicorandil, lemakalim, isoproterenol, prostaglandin E1, sodium nitroprusside, and 8-bromo-cGMP, agents that act by a variety of mechanisms, were not decreased. These results are consistent with the hypothesis that efferent vagal stimulation releases acetylcholine, which dilates the pulmonary vascular bed by stimulating the production of nitric oxide or a labile nitroso compound from L-arginine. PMID- 1735137 TI - Indexing tricarboxylic acid cycle flux in intact hearts by carbon-13 nuclear magnetic resonance. AB - Although the tricarboxylic acid (TCA) cycle is the prime means of carbon metabolism for energy generation in normal myocardium, the noninvasive quantification of TCA cycle flux in intact cardiac tissues is difficult. A novel approach for estimating citric acid cycle flux using 13C nuclear magnetic resonance (NMR) is presented and evaluated experimentally by comparison with measured myocardial oxygen consumption over a wide range of cardiac contractile function in intact, beating rat hearts. Continuous series of 13C NMR spectra, obtained after the introduction of [2-13C]acetate as substrate, quantified the time course of 13C appearance in the carbon positions of myocardial glutamate, which are sequentially enriched via citric acid cycle metabolism. A TCA cycle flux parameter was calculated using the premise that TCA cycle flux is inversely proportional to the time difference between 13C appearance in the C-4 and C-2 positions of glutamate (glutamate delta t50 [minutes]), which are enriched in subsequent "turns" of the TCA cycle. This TCA cycle flux parameter, termed KT, correlated strongly with myocardial oxygen consumption over a range of developed pressures in hearts perfused with 5 mM acetate (r = 0.98, p less than 0.001), as well as in separate studies in hearts perfused with 5 mM glucose and 0.5-0.8 mM acetate (r = 0.94, p less than 0.001). Results of numerical modeling of 13C glutamate kinetics suggest that this TCA cycle flux parameter, KT, is relatively insensitive to changes in metabolite pool sizes that could occur during metabolism of other substrates or during conditions of altered oxygen availability. Additional studies in separate hearts indicated that the time course of 13C appearance in citrate, which is predominantly mitochondrial in the rat heart, is similar to that in glutamate, further supporting the premise that the described 13C NMR parameters reflect mitochondrial citric acid cycle activity in intact cardiac tissues. PMID- 1735138 TI - Early changes in extracellular potassium in ischemic rabbit myocardium. The role of extracellular carbon dioxide accumulation and diffusion. AB - The role of local accumulation and diffusion of CO2 to modify cellular loss and extracellular accumulation of K+ during the initial, reversible phase of myocardial ischemia was investigated in isolated, cylindrical papillary muscles of the rabbit. The muscles were blood-perfused through their vascular tree and placed in a (permanently flowing) humidified gas mixture with predetermined partial pressures of N2, O2, and CO2. Ischemia was produced by total arrest of perfusion and O2 withdrawal from the gas mixture. With surface PCO2 kept constant during ischemia, [K+]o varied markedly with muscle geometry. After 10 minutes of ischemia, K+ accumulation was approximately 2.5 mM in muscles with a radius of 0.35 mm and approximately 14 mM in muscles with a radius of 0.9 mm, indicating that a large fraction of K+ accumulation was dependent on diffusion of a volatile metabolite. Computer simulation of CO2 accumulation and diffusion within a tissue cylinder suggested a close phenomenological relation between PCO2 and [K+]o in ischemia. This was confirmed by the finding that an increase of tissue PCO2 in small cylinders before or during ischemia by externally applied CO2 produced an increase in K+ accumulation. The importance of CO2 diffusion for local inhomogeneities in K+ within the same preparation was demonstrated by showing [K+]o gradients with simultaneous or consecutive measurements between the papillary muscle cylinders and the adjacent septum and within 300 microns from the surface of the papillary muscle cylinders. These gradients predict an inhomogeneity of impulse conduction that might contribute to the genesis of ventricular arrhythmias. Besides the demonstration that accumulation and diffusion introduce inhomogeneities of [K+]o in ischemia, our results suggest that a significant component of cellular ischemic K+ loss is associated with production and extrusion of metabolic acid. On the basis of previous measurements of pHo and pHi in identical conditions, possible mechanisms of ischemic cellular K+ loss are discussed. PMID- 1735139 TI - Vascular responses to activated leukocytes after regression of atherosclerosis. AB - Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735140 TI - Brain ouabain and central effects of dietary sodium in spontaneously hypertensive rats. AB - High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular alpha 2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 mumol), 2) normal sodium intake (NNa, 101 mumol), and 3) HNa (1,370 mumol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735141 TI - Signal transduction by G proteins in cardiac tissues. AB - The role of G proteins in mediating the responses of the heart to circulating catecholamines and to the influences of the autonomic nervous system is of special interest to cardiologists. It is evident that G proteins are essential links in the cascade of biochemical events that ensure when neurotransmitters and hormones interact with receptors on myocardial cells. It is likely [corrected] that dysfunction of G proteins plays a role in cardiovascular pathophysiology. With current methodologies, especially molecular biological and recombinant DNA techniques, and with transgenic animal models that can relate physiological function and specific gene dosage, some cardiovascular diseases may be traced to G protein-related defects. PMID- 1735142 TI - Diagnosis of thoracic aortic dissection. Magnetic resonance imaging versus transesophageal echocardiography. AB - BACKGROUND: Aortic dissection requires prompt and reliable diagnosis to reduce the high mortality. The purpose of this study was to assess the reliability of both ECG-triggered magnetic resonance imaging (MRI) and transesophageal two dimensional echocardiography combined with color-coded Doppler flow imaging (TEE) for the diagnosis of thoracic aortic dissection and associated epiphenomena. METHODS AND RESULTS: Fifty-three consecutive patients with clinically suspected aortic dissection were subjected to a dual noninvasive imaging protocol in random order; imaging results were compared and validated against the independent morphological "gold standard" of intraoperative findings (n = 27), necropsy (n = 7), and/or contrast angiography (n = 53). No serious side effects were encountered with either imaging method. In contrast to a precursory screening transthoracic echogram, the sensitivities of both MRI and TEE were 100% for detecting a dissection of the thoracic aorta irrespective of its location. The specificity of TEE, however, was lower than the specificity of MRI for a dissection (TEE, 68.2% versus MRI, 100%; p less than 0.005), which resulted mainly from false-positive TEE findings confined to the ascending segment of the aorta (TEE, 78.8% versus MRI, 100%; p less than 0.01). In addition, MRI proved to be more sensitive than TEE in detecting the formation of thrombus in the false lumen of both the aortic arch (p less than 0.01) and the descending segment of the aorta (p less than 0.05). There were no discrepancies between the two imaging techniques in detecting the site of entry to a dissection, aortic regurgitation, or pericardial effusion. CONCLUSIONS: Both MRI and TEE are atraumatic, safe, and highly sensitive methods to identify and classify acute and subacute dissections of the entire thoracic aorta. TEE, however, is associated with lower specificity for lesions in the ascending aorta. These results may still favor TEE as a semi invasive diagnostic procedure after a precursory screening transthoracic echogram in suspected aortic dissection, but they establish MRI as an excellent method to avoid false-positive findings. Anatomic mapping by MRI may emerge as the most comprehensive approach and morphological standard to guide surgical interventions. PMID- 1735143 TI - Multicenter experience with balloon mitral commissurotomy. NHLBI Balloon Valvuloplasty Registry Report on immediate and 30-day follow-up results. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry Participants. AB - BACKGROUND: Balloon mitral commissurotomy can increase mitral valve areas and reduce symptoms in selected patients with mitral stenosis. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry was organized to address concerns regarding differences in patient selection and technique and to report the current clinical outcome. METHODS AND RESULTS: In 24 cooperating centers, 738 patients had balloon mitral commissurotomy. Baseline clinical, echo Doppler, and cardiac catheterization data, procedure details, and hemodynamic and 30-day clinical outcome were reported. Overall, 81% of the patients were women (mean age, 54 +/- 15 years), and 24% had moderate or severe other valvular lesions. When single- and double-balloon procedures were compared, the final mitral valve area was larger (1.7 +/- 0.7 versus 2.0 +/- 0.8 cm2, p = 0.0009), increase in mitral regurgitation was similar (4% versus 12%, p = 0.08), and interatrial shunts occurred more frequently (2% versus 12%, p = 0.04) after double-balloon procedures. Increase in mitral valve area was weakly related to mitral valve morphology as assessed by an echo score (r = -0.15). Multivariate predictors of improved clinical status at 30 days were cases performed in larger-volume centers, baseline mitral valve area greater than 0.5 cm2, and age less than 70 years. At 30-day follow-up, 4% of the patients with completed procedures had mitral valve surgery, 3% had died, and 83% had their overall condition improved. Patients with mixed mitral stenosis or regurgitation and isolated mitral stenosis had a similar course, but fewer patients with multivalve disease became asymptomatic. CONCLUSIONS: Balloon mitral commissurotomy, as practiced in a broad range of experienced centers, produced significant short-term hemodynamic and clinical improvements. Balloon mitral commissurotomy can be considered an effective treatment option in patients with symptomatic mitral stenosis. PMID- 1735144 TI - Complications and validity of pulmonary angiography in acute pulmonary embolism. AB - BACKGROUND: The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED: METHODS AND RESULTS: Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p less than 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%. CONCLUSIONS: The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk. PMID- 1735145 TI - Five- to fifteen-year follow-up after Fontan operation. AB - BACKGROUND: The purpose of this study was to estimate survival and quality of outcome and assess factors associated with outcome for patients out 5 to 15 years from their Fontan operation. METHODS AND RESULTS: We studied 352 patients who had the Fontan operation prior to 1985. The overall 1-, 5-, and 10-year survival was 77%, 70%, and 60%, respectively. The following factors were significantly associated with lower survival: univentricular heart or complex congenital anomalies other than tricuspid atresia, early calendar year of operation, heterotaxia syndromes, early age at operation, increased pulmonary artery pressure, atrioventricular valve dysfunction, and higher (worse) New York Heart Association class. Reoperations were necessary for 103 of the 352 patients. At least 20% of the survivors have or have had cardiac arrhythmias requiring antiarrhythmic medication or mechanical pacemaker insertion. Between 7% and 10% of the patients have had or had protein-losing enteropathy/hypoproteinemia. At 5 years postoperatively, 122 patients (34.7%) were alive with a better New York Heart Association functional classification than preoperatively. Fifty-eight patients (16.5%) were alive and in the same functional classification, but 126 (35.8%) died within the first 5 years or were in a worse functional classification. Thirty-nine patients were doing excellently and 29 patients poorly 5 years after the operation. Of the surviving patients, 43% can do as much exercise as their peers, whereas 3% are incapable of exercise. CONCLUSIONS: To assure good functional long-term outcome in addition to survival, clinicians must exclude from selection for Fontan operation patients known to be at high risk for death or poor outcome. PMID- 1735146 TI - Baroreflex sensitivity and heredity in essential hypertension. AB - BACKGROUND: Abnormalities in baroreflex control of heart rate may be important in the pathogenesis of essential hypertension. METHODS AND RESULTS: To investigate the influence of heredity on baroreflex function, we measured baroreflex sensitivity in 40 untreated patients with essential hypertension grouped by the presence (FH+) or absence (FH-) of a family history of hypertension and in 24 normotensive counterparts. Baroreflex sensitivity was assessed by both high pressure (phenylephrine bolus) and low-pressure (amyl nitrite inhalation) stimuli. Subject groups were matched for age, blood pressure, body weight, and race. Baroreflex sensitivity (in milliseconds per millimeter of mercury) assessed by amyl nitrite inhalation was 24.3 +/- 2.8 in FH- normotensives, 12.3 +/- 1.7 in FH+ normotensives, 15.4 +/- 3.3 in FH- hypertensives, and 8.1 +/- 1.2 in FH+ hypertensives. Baroreflex sensitivity assessed by phenylephrine bolus was 28.8 +/ 5.6 in FH- normotensives, 19.3 +/- 2.8 in FH+ normotensives, 19.1 +/- 2.0 in FH- hypertensives, and 13.6 +/- 1.3 in FH+ hypertensives. Two-factor analysis of variance showed significant effects on baroreflex sensitivity for blood pressure status (normotensive versus hypertensive) and for family history of hypertension. After control line (controlling) for the effects of several variables, including age, mean arterial pressure, body weight, and race through multiple linear regression analysis, the effect of family history of hypertension on baroreflex sensitivity was still highly significant. Indeed, of all variables investigated, family history of hypertension was the strongest unique baroreflex sensitivity predictor. CONCLUSIONS: These data suggest that the impairment in baroreflex sensitivity in hypertension is in part genetically determined and may be an important hereditary component in the pathogenesis of essential hypertension. PMID- 1735147 TI - Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure. AB - BACKGROUND: Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS: We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS: Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation. PMID- 1735148 TI - Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy. AB - BACKGROUND: We performed a comparative study on Ca2+ release activity of the sarcoplasmic reticulum and calcium sensitivity of contractile apparatus of chemically skinned myocardial fibers obtained from four nonfailing human hearts and 13 excised hearts from patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Ca2+ sensitivity of contractile apparatus was studied by following the isometric tension developed by chemically skinned myocardial fibers challenged with solutions of decreasing pCa. Ca2+ release from sarcoplasmic reticulum was monitored indirectly by measurement of the isometric tension developed by skinned fibers challenged with caffeine. We observed no significant difference of Ca2+ sensitivity and cooperativity between normal myocardium (pCa50 = 6.00 +/- 0.05; Hill coefficient, nHill = 2.07 +/- 0.10) and dilated cardiomyopathy (pCa50 = 6.03 +/- 0.07; nHill = 2.72 +/- 0.30) when the fibers were stretched to 130% of the resting length. We also found that both in normal myocardium and dilated cardiomyopathy, stretching to 150% of the resting length increased the Ca2+ sensitivity of the contractile system; pCa50 = 6.21 +/- 0.01 and 6.13 +/- 0.04 in normal and dilated cardiomyopathy, respectively, whereas in dilated cardiomyopathy there was a decrease of Hill coefficient with stretching that was not observed in the control group. The caffeine threshold in idiopathic dilated cardiomyopathy was markedly increased compared with the control group, 1.94 +/- 0.27 mmol/l and 0.29 +/- 0.04 mmol/l caffeine, respectively, whereas there were no significant differences in the extent and rate of caffeine-induced Ca2+ release. CONCLUSIONS: These results indicate that in idiopathic dilated cardiomyopathy there is no alteration of contractile and regulatory proteins; on the contrary, the gating mechanism of the Ca2+ release channel of sarcoplasmic reticulum is abnormal, suggesting a possible involvement of the excitation contraction coupling in the pathogenesis of this disease. It should also be taken into account, however, that the increased caffeine threshold in dilated cardiomyopathy would be a result of the enhanced resistance to the skinning procedure secondary to the modification of lipid species and/or content in sarcoplasmic reticulum membrane. PMID- 1735149 TI - One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI) Phase II Trial. AB - BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial randomized 3,339 patients to either an invasive (INV, n = 1,681) or a conservative (CON, n = 1,658) strategy after intravenous recombinant tissue-type plasminogen activator (rt-PA) for acute myocardial infarction. METHODS AND RESULTS: The patients assigned to the INV strategy routinely underwent cardiac catheterization, and when anatomically appropriate, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting 18-48 hours after infarction. CON patients had these procedures only in response to the occurrence of spontaneous or provoked ischemia. One-year follow-up data are available in 3,316 patients (99.3%). The primary trial end point, death and nonfatal reinfarction, occurred in 14.7% of INV patients and in 15.2% of CON patients (p = NS). When analyzed individually, there was no difference (p = NS) in death (INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two groups. Anginal status at 1 year was also similar. Cardiac catheterization and PTCA were performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and 20.5%, respectively) patients. At 1 year, the cumulative number of patients who underwent coronary bypass surgery (INV, 17.5%; CON, 17.3%) was similar in the two groups. CONCLUSIONS: The INV and CON strategies resulted in similar favorable outcomes at 1 year of follow-up. In particular, the rates of mortality and reinfarction were not different and were impressively low in both groups. One possible advantage of the INV strategy was detected in subgroup analyses. In patients with a history of myocardial infarction, the data are suggestive that 1-year mortality was lower in INV patients (10.3%) than in CON patients (17.0%) (p = 0.03). PMID- 1735150 TI - Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy. AB - BACKGROUND: Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile phenotype) preferentially express smooth muscle myosin, proliferating smooth muscle cells (synthetic phenotype) have been shown to preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed the expression of a recently cloned isoform of human nonmuscle myosin heavy chain (MHC-B) in fresh human restenotic lesions. METHODS AND RESULTS: A total of 10 lesions, including four restenosis (three superficial femoral arterial lesions and one saphenous vein bypass lesion) and six primary (four superficial femoral arterial lesions and two coronary arterial lesions) obtained percutaneously by directional atherectomy, were processed for examination by in situ hybridization. In total, 150 tissue sections of restenotic lesions (66 sections), primary lesions (78 sections), and normal internal mammary artery (six sections) were hybridized with the nonmuscle MHC-B probe. Restenotic lesions showed intense hybridization to the nonmuscle MHC B cRNA probe, as demonstrated by a clustering of more than 20 grains per cell nucleus in 80% of the cells examined within a high-power field (x250); in contrast, an equivalent degree of hybridization was observed in only 7% of cells within primary lesions (p less than 0.001). Results of immunocytochemistry using monoclonal antibody to smooth muscle actin indicated that cells demonstrating strong hybridization were smooth muscle in origin. CONCLUSIONS: These findings demonstrate that 1) human vascular tissue obtained by percutaneous directional atherectomy constitutes appropriate biopsy material for gene expression studies at the mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance among restenotic versus primary vascular stenoses. These observations thus provide a rational basis to explore restenotic lesions on a larger scale to identify genes that are activated in these lesions and establish potential targets for future gene therapy. PMID- 1735151 TI - Migratory activity of human smooth muscle cells cultivated from coronary and peripheral primary and restenotic lesions removed by percutaneous atherectomy. AB - BACKGROUND: The successful cultivation of human smooth muscle cells (SMC) from coronary and peripheral atherosclerotic lesions removed by percutaneous directional atherectomy is described. METHODS AND RESULTS: Sixty-seven patients in whom plaque material was obtained compose the study population. A total of 73 lesions from both coronary (n = 38) and peripheral (n = 35) arteries of primary (n = 50) and restenotic origin (n = 23) were studied. Successful cultivation was significantly (p less than 0.001) dependent on the quantity of plaque material submitted. Fifty-five percent of patients in whom atherectomy specimens were removed from coronary lesions yielded an adequate SMC population in comparison to 89% of those from peripheral arteries (p less than 0.01). Cultivation was not dependent on the age and sex of patients, lesion origin, risk factors, medications, or incidence of unstable angina. In an attempt to quantify SMC activity, migratory velocity was measured with a computer-assisted motion analysis system. SMC migratory velocity was found to be significantly (p less than 0.001) greater in restenotic than in primary plaque material. This finding was confirmed for both coronary and peripheral lesions. CONCLUSIONS: Our data suggest that elevated SMC migratory activity may be an important mechanism in the development of restenotic lesions. PMID- 1735152 TI - Electrogram criteria for identification of appropriate target sites for radiofrequency catheter ablation of accessory atrioventricular connections. AB - BACKGROUND: Catheter ablation of accessory atrioventricular (AV) connections using radiofrequency current has been demonstrated to be effective in the majority of patients with the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia involving a concealed accessory AV connection. However, electrogram criteria have not been established to guide attempts at radiofrequency catheter ablation. METHODS AND RESULTS: The characteristics of local electrograms recorded at successful and unsuccessful sites of radiofrequency catheter ablation were determined in 132 patients. Electrograms recorded at a total of 438 sites were analyzed: 338 recorded during ablation of 90 manifest accessory AV connections and 100 recorded during ablation of 44 concealed accessory AV connections. During ablation of manifest accessory AV connections, the independent predictors of outcome were electrogram stability (p less than 0.001), the interval between activation of the ventricular electrogram and onset of the QRS complex (p less than 0.001), and the presence of an accessory AV connection potential (p less than 0.001). Radiofrequency energy delivery at sites demonstrating stable electrograms, a probable or possible accessory AV connection potential, and activation of the local ventrical electrogram before the onset of the QRS complex had a 57% probability of success compared with a 3% probability of success at sites without these features. During ablation of concealed accessory AV connections, the independent predictors of outcome were electrogram stability (p = 0.02), the presence of an accessory AV connection potential (p = 0.05), and the presence of retrograde continuous electrical activity (p = 0.04). Sites demonstrating a stable local electrogram, an accessory AV connection potential, and retrograde continuous electrical activity had an 82% probability of success compared with only a 5% probability of success at sites demonstrating none of these features. CONCLUSIONS: The local electrogram parameters of greatest importance in predicting the success or failure of radiofrequency catheter ablation of accessory AV connections are electrogram stability, the presence of an accessory AV connection potential, and the timing of ventricular activation relative to the QRS complex (for manifest accessory AV connections) or retrograde continuous electrical activity (for concealed accessory AV connections). Awareness of these variables during attempts at radiofrequency catheter ablation of accessory AV connections may minimize the number of unnecessary applications of radiofrequency energy. PMID- 1735153 TI - Physiological substrate for antidromic reciprocating tachycardia. Prerequisite characteristics of the accessory pathway and atrioventricular conduction system. AB - BACKGROUND: Although the anatomic "substrate" for the occurrence of antidromic reciprocating tachycardia (ART) has been previously examined, the underlying physiological substrate for this unusual arrhythmia in patients with the Wolff Parkinson-White syndrome has not been thoroughly characterized. METHODS AND RESULTS: The electrophysiological properties of the accessory pathway and normal ventriculoatrial conduction system in 30 patients with ART and a single accessory pathway were compared with those observed in a control group of 36 patients without this arrhythmia to elucidate the critical physiological substrate essential for the development and maintenance of ART. Inducible ART had a mean cycle length of 286 +/- 31 msec. The average retrograde ventriculoatrial conduction system effective refractory period in ART patients was significantly less than that in the control group (244 +/- 32 versus 291 +/- 46 msec, p = 0.0002). All of the ART patients showed retrograde conduction over the normal conduction system at cycle lengths of less than or equal to 360 msec; 23 had 1:1 conduction to less than or equal to 300 msec, and 16 showed 1:1 propagation at cycle lengths of less than or equal to 260 msec. The shortest cycle length accompanied by 1:1 retrograde propagation over the normal conduction system in patients with ART was also significantly less than that observed in the control group (274 +/- 39 versus 347 +/- 73 msec, p less than 0.001). The accessory pathway anterograde ERP in ART patients with 1:1 retrograde conduction over the normal ventriculoatrial conduction system at cycle lengths of less than or equal to 360 was significantly less than that seen in comparable control patients (247 +/- 23 versus 284 +/- 56 msec, p = 0.001), and the accessory pathway location was significantly further from the atrioventricular node in 21 patients with ART undergoing surgery than that in 22 operated control patients (3.8 +/- 0.8 versus 2.9 +/- 0.8 mapping units, p = 0.0025) who also had retrograde ventriculoatrial conduction to cycle lengths of less than or equal to 360 msec. No significant differences in anterograde atrioventricular conduction system properties, retrograde accessory pathway refractoriness, or shortest ventricular pacing cycle lengths maintaining 1:1 conduction via the accessory pathway were observed between groups. CONCLUSIONS: This quantitative characterization of the properties of conduction and refractoriness of both the accessory pathway and ventriculoatrial conduction system and the relation between these characteristics and the accessory pathway location in ART patients provides additional insight into the prerequisites for the initiation and maintenance of this rhythm disturbance. PMID- 1735154 TI - Incidence and mechanism of interruption of reentrant ventricular tachycardia with rapid ventricular pacing. AB - BACKGROUND: Information concerning the electrophysiological characteristics of the reentrant circuit is still limited. To understand the incidence and mechanism of pacing-induced interruption of ventricular tachycardia (VT), rapid pacing was performed to entrain VT, and the local electrogram at the VT origin and the surface electrocardiogram were analyzed. METHODS AND RESULTS: Among 25 patients, evidence of transient entrainment was confirmed in 20 patients, but the critical paced cycle length at which VT was interrupted was obtained in 13 patients when the paced cycle length was decreased in steps of 10 msec. During pacing at the critical cycle length (defined as block cycle length), changes in the local electrogram at VT origin were confirmed in all of the 13 patients; that is, 1) a change in morphology and 2) a change in the timing of activation: a sudden shortening in the stimulus to local electrogram time (third entrainment criterion by Waldo). The two changes mean that the exit is activated from a different direction (retrograde capture) because of an orthodromic block in the slow conduction zone. The QRS complex in the surface electrocardiogram showed a change in configuration from the fusion complex to the fully paced one at the same time when the exit was captured antidromically. CONCLUSIONS: Based on our observations in these patients, ventricular tachycardia interruption is very often associated with orthodromic block in the reentrant circuit at a critical cycle length of rapid pacing. PMID- 1735155 TI - Prevalence, circumstances, mechanisms, and risk stratification of sudden cardiac death in unipolar single-chamber ventricular pacing. AB - BACKGROUND: Permanent cardiac pacing is well established for the improvement of prognosis and quality of life in patients with severe bradycardia. However, sudden cardiac death still remains an unresolved problem, as it occurs in approximately 20-30% of paced patients. This 2-year follow-up study was directed at prospectively assessing prevalence, circumstances, and mechanisms of sudden death in 2,021 permanently paced patients. METHODS AND RESULTS: During the observation period, 220 patients (11%) died (mean pacing interval, 50.5 +/- 7 months). Lethal cerebrovascular events in 66 of 220 patients (30%) and sudden death in 49 of 220 patients (23%) were the two most frequently reported modes of death. Nonsudden (first year, 20%; subsequent years, 6.9%; p less than 0.01) and sudden death mortality rate (4% versus 1.8%, p less than 0.05) were highest during the first year. Mortality was unrelated to the patient's activity status at the time of death. Sudden cardiac death occurred more often in male patients (increased risk, 1.7 versus female patients; p less than 0.001) and patients younger than 60 years of age (5.2 versus patients older than 60 years, p less than 0.001). Patients with severe bradycardia (sudden death rate, 28%), severe atrioventricular block (25%), or atrial fibrillation with low ventricular rate (25%) before pacemaker implantation were more likely to suffer from sudden cardiac death than patients with previous syncopal attacks (sudden death rate, 15%) or sick sinus syndrome (17%). The highest incidence of sudden death was observed in patients with bifascicular and trifascicular bundle branch block. In this group, 35% of patients died suddenly during the follow-up period compared with 18% of patients without bundle branch block. In a subsequent study in 90 consecutive patients with various types of bundle branch block, undersensing of up to 13% of ectopic ventricular beats occurred in patients with bifascicular block. Pacing-induced tachyarrhythmias and ventricular fibrillation were documented in 10% of undersensed ectopic ventricular beats as well as in the setting of atrial fibrillation associated with ventricular arrhythmias. CONCLUSIONS: Young age, male sex, and a severely diseased heart indicated by the presence of bifascicular and trifascicular bundle branch block are the strongest predictive clinical parameters for sudden cardiac death, especially in the first year after pacemaker implantation. PMID- 1735156 TI - Variant angina pectoris. Role of coronary spasm in the development of fixed coronary obstructions. AB - BACKGROUND: It has been suggested that recurring coronary artery spasm may lead to the development of fixed atherosclerotic coronary obstructions. METHODS AND RESULTS: We studied 10 patients with typical Prinzmetal's variant angina in whom the disease remained active for years and in whom occlusive coronary spasm occurred reproducibly at the same arterial site during repeat coronary arteriography (25 +/- 12 months after initial angiography). At initial evaluation, four patients had significant (greater than or equal to 50% fixed coronary diameter reduction) one-vessel coronary artery disease, and six had nonsignificant disease. Spasm developed at stenotic sites (20-65% diameter reduction) in nine patients and at an angiographically normal site in one patient. Progression of coronary disease was assessed in 62 segments: 10 spastic (of which nine were stenotic) and 52 nonspastic (eight stenotic and 44 angiographically normal), using computerized arteriography. Mean diameters (millimeters) of spastic segments, nonspastic stenoses, and angiographically normal nonspastic segments were not significantly different at first and second arteriograms (1.52 +/- 0.14 versus 1.43 +/- 0.21, 1.32 +/- 0.17 versus 1.12 +/- 0.23, and 2.40 +/- 0.12 versus 2.42 +/- 0.12, respectively). Stenosis progression (from 65% diameter reduction to total occlusion) occurred in one patient at a spastic site and in two at nonspastic sites (from 34% to 65% and from 84% to 100%). Complicated stenoses suggestive of plaque fissuring were not observed during the study. CONCLUSIONS: In patients with chronic Prinzmetal's variant angina without myocardial infarction, stenosis progression was not frequently observed at spastic sites despite the recurrence of focal coronary spasm over relatively long periods of time. PMID- 1735157 TI - Regional thallium uptake in irreversible defects. Magnitude of change in thallium activity after reinjection distinguishes viable from nonviable myocardium. AB - BACKGROUND: Thallium reinjection immediately after stress-redistribution imaging identifies ischemic but viable myocardium in as many as 50% of the regions characterized by conventional redistribution imaging as irreversibly injured. However, we have previously shown that some regions in which irreversible defects persist despite reinjection are metabolically active, and hence viable, by positron emission tomography. In the current study, we determined whether the severity of reduction in thallium activity within irreversible defects on redistribution images and the magnitude of change in regional thallium activity after reinjection can further discriminate viable from nonviable myocardium in such defects. METHODS AND RESULTS: We studied 150 patients with coronary artery disease by exercise thallium tomography using the rest-reinjection protocol. The three sets of images (stress, redistribution, and reinjection) were then analyzed quantitatively. The increase in regional thallium activity from redistribution to reinjection was computed, normalized to the increase observed in a normal region, and termed "differential uptake." Of the 175 myocardial regions designated to have irreversible thallium defects on conventional 3-4 hour redistribution images, 132 had only mild-to-moderate reduction in thallium activity (51-85% of normal activity), and 43 had severe reduction in thallium activity (less than or equal to 50% of normal activity). Thallium reinjection resulted in enhanced relative activity in 60 of 132 (45%) of the mild-to-moderate irreversible defects and 22 of 43 (51%) of the severe irreversible defects, leaving roughly half of these defects remaining irreversible after reinjection. However, in regions that appeared to remain irreversible despite reinjection, the magnitude of differential uptake differed between mild-to-moderate (74 +/- 14%) and severe (35 +/- 16%) irreversible defects (p less than 0.001). All regions with mild-to moderate defects demonstrated greater than 50% differential uptake after reinjection. In contrast, all except two of the regions with severe irreversible defects demonstrated differential uptake of less than 50%. Fifteen patients also underwent positron emission tomography at rest with 18F-fluorodeoxyglucose (FDG) and 15O-water. FDG uptake was present in 91% of regions with mild-to-moderate reduction in thallium activity, and the results of differential uptake and FDG data were concordant in 81% of these regions. CONCLUSIONS: These data indicate that the magnitude of thallium uptake after reinjection differs between mild-to moderate and severe irreversible defects on standard 3-4 hour redistribution images. The substantial differential uptake of thallium (greater than 50%) after reinjection in mild-to-moderate defects, even when relative thallium activity does not increase appreciably (and the defect appears to remain irreversible), coupled with preserved metabolic activity by positron emission tomography, supports the concept that such mild-to-moderate irreversible defects represent viable myocardium. PMID- 1735158 TI - Evidence of genetic heterogeneity in five kindreds with familial hypertrophic cardiomyopathy. AB - BACKGROUND: Recently, two families with hypertrophic cardiomyopathy have been shown to have mutations in the cardiac beta-myosin heavy chain gene (beta-MHC) located on the long arm of chromosome 14. METHODS AND RESULTS: We have performed linkage analysis of five newly ascertained pedigrees with more than 50 chromosomal markers detecting polymorphisms. Our findings confirm the linkage to beta-MHC gene locus on chromosome 14 in one family (LOD score, 4.50) and suggest linkage to the same gene in another kindred. Chromosome 14 markers were not linked to the disease gene in the other three kindreds, however, and a test for genetic heterogeneity was statistically significant. Moreover, markers for the beta-MHC gene identified affected individuals who were recombinants with respect to this gene and the disease phenotype in these three kindreds. CONCLUSIONS: These results provide conclusive evidence that hypertrophic cardiomyopathy in separate families is caused by mutations in disease genes at two or more locations in the genome. PMID- 1735159 TI - Prevalence of cardiovascular risk factors in rural and urban Costa Rica. AB - BACKGROUND: Coronary artery disease (CAD) is becoming more prevalent in developing countries, particularly in the urban areas, in contrast to the CAD mortality trends observed in some industrialized nations. METHODS AND RESULTS: We determined the prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, obesity, total cholesterol greater than or equal to 240 mg/dl and greater than or equal to 200 less than or equal to 239 mg/dl, low density lipoprotein (LDL) cholesterol greater than or equal to 160 mg/dl and greater than 130 less than or equal to 159 mg/dl, and high density lipoprotein (HDL) cholesterol less than 35 mg/dl) in 222 men and 243 women from rural and urban areas of Puriscal, Costa Rica, using the American Cholesterol Education Program guidelines. Urban Puriscal men had a significantly (p less than 0.05) higher prevalence of borderline high-risk total cholesterol (26% versus 14%), borderline high-risk LDL cholesterol (21% versus 11%), smoking (32% versus 13%), and higher prevalence of low HDL cholesterol (34% versus 24%), hypertension (16% versus 13%), diabetes (4.5% versus 2.7%), obesity (21% versus 14%), and saturated fat intake greater than 15% of calories (14% versus 7%) than rural men from Puriscal. No significant differences between rural and urban women were found for any of the cardiovascular risk factors. Urban Puriscal residents were also more sedentary than rural Puriscal residents. CONCLUSIONS: These data indicate that modifiable risk factors are more prevalent in urban than in rural Puriscal, Costa Rica, particularly in men. PMID- 1735160 TI - Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction. AB - BACKGROUND: Recent data from this laboratory indicate that pretreatment with adenosine can protect the heart against infarction via A1-receptors, but because of systemic hypotension, adenosine had to be given into the coronary circulation. METHODS AND RESULTS: In this study, we tested whether the protection could be achieved by intravenous administration of the A1-selective adenosine agonists N6 (phenyl-2R-isopropyl)-adenosine (PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA). Nine groups of open-chest anesthetized rabbits were subjected to 30 minutes of regional coronary ischemia and 3 hours of reperfusion. Infarct size was determined by tetrazolium staining. Control hearts receiving no treatment had 38 +/- 4% of the risk zone infarcted. Preconditioning with 5 minutes of ischemia and 10 minutes of reperfusion before ischemia limited the infarct to 8 +/- 4%. Intravenous PIA 15 minutes before 30-minute ischemia also limited infarct size to 6 +/- 2% at the highest dose. CCPA offered similar protection. When the PIA was given at reperfusion, infarct size was 46 +/- 6%, indicating that receptor activation must precede ischemia to protect. Pretreatment with CGS 21680, a selective A2-receptor agonist, caused identical hypotension but failed to limit infarct size (43 +/- 3%), indicating again that the A1-receptor is involved. When rabbits pretreated with PIA were paced at 220 beats per minutes, PIA still limited infarct size (16 +/- 4%), indicating that protection was not the result of bradycardia. CONCLUSIONS: These results indicate that stimulation of adenosine A1-receptors causes the heart to become resistant to ischemia and that this protection can be achieved with intravenous administration of A1-selective agents. PMID- 1735161 TI - High-current stimuli to the spared epicardium of a large infarct induce ventricular tachycardia. AB - BACKGROUND: Previous studies have demonstrated that both ventricular tachycardia (VT) and ventricular fibrillation (VF) may begin as figure-eight reentry: VT with a longer cycle length from spared tissue adjacent to an infarct by programmed stimulation and VF with a shorter cycle length from noninfarcted tissue by a large premature S2 stimulus. These results suggest that the type of tissue or cycle length of the arrhythmia rather than the mode of induction determines whether the figure eight becomes sustained VT or degenerates into VF. Thus, a protocol similar to that by which a VF threshold is determined may induce VT rather than VF when performed in the spared tissue over an infarct. METHODS AND RESULTS: In 10 dogs, 4 days after occlusion-reperfusion of the left anterior descending coronary artery, 10 S1 stimuli were delivered from a total of 34 right and left ventricular sites outside the infarct. An epicardial S2 stimulus over the infarct was increased in 10-mA steps and introduced in diastole at decreasing cycle lengths of 5 msec until VT or VF was induced. Sustained monomorphic figure eight VT was induced from 24 S1 sites and VF from nine (p = 0.03). The mean cycle lengths for the initial six arrhythmic cycles was 152 +/- 33 msec for VT and 115 +/- 13 msec for VF (p less than 0.001). Mean transmural infarct extent was 80% in five dogs with only VT, 63% in three dogs with both VT and VF, and 15% in two dogs with only VF. Different morphologies of VT were induced by changing the S1 site, the S2 strength, or the S1S2 coupling interval. In 25 of the 34 arrhythmias, the central part of the initial figure-eight pathway was oriented opposite the S1 activation sequence in that region. CONCLUSIONS: A large S2 stimulus over a nontransmural infarct induces VT if the spared myocardium is thin. This study introduces a useful technique for inducing sustained monomorphic VT in which the location and direction of the figure-eight pathway are known a priori and in which different morphologies of sustained VT can be produced by changing the S1 site. PMID- 1735162 TI - Acute hibernation and reperfusion of the ischemic heart. AB - BACKGROUND: Recovery from prolonged low-flow ischemia was studied in isolated, isovolumically beating neonatal piglet hearts (n = 11) and compared with controls (n = 5). METHODS AND RESULTS: Hearts were perfused with red blood cell-enhanced Krebs-Henseleit buffer with physiological oxygen-carrying capacity. Left ventricular mechanical function was assessed with a fluid-filled balloon. Measurements of peak systolic pressure, pressure-rate product (PRP), and +dP/dtmax were obtained at various filling pressures. Myocardial oxygen delivery and metabolism (MVO2) and lactate uptake were measured at 30-minute intervals. Control data were obtained with coronary flow (CF) set at 2 ml.min-1.g-1. CF was then reduced to 0.2 ml.min-1.g-1 for 2 hours. Thereafter, reperfusion was instituted at control levels. Hearts not subjected to ischemia were studied at identical time intervals. In these, function remained at greater than 80% after more than 3.5 hours of study. Reduction of CF to 10% was accompanied by an abrupt diminution in function (pressure-rate product) and MVO2 to 20% of control and by lactate release. These measures remained constant for the full 2 hours of ischemia. Incremental return of CF caused a lockstep increase in mechanical function and metabolism. At 30 minutes of reperfusion, PRP was 78% of time matched controls (p = 0.05), and dP/dtmax did not differ. Increasing calcium to 5 mmol/l returned PRP (and dP/dtmax) to preischemia levels. Myocardial ATP and creatine phosphate concentrations were identical in both groups, although glycogen was lower in the ischemic hearts. CONCLUSIONS: Acute hibernation is associated with protection of the in vitro heart from prolonged normothermic ischemia. Systolic function was only modestly lower, and velocity (dP/dtmax) did not differ from control hearts. The minimal "stunning" was fully reversible with calcium. PMID- 1735163 TI - Importance of intraluminal pressure on hemodynamics and vasoconstriction responses of stenotic arteries. AB - BACKGROUND: Clinical and morphological studies clearly indicate that most human coronary artery stenoses are capable of vasomotion. Variable ischemic thresholds, ischemia unrelated to work load, and variant angina further show the presence and importance of vasoconstriction in coronary artery stenosis. Despite the importance of vasoconstriction, the effect of intraluminal pressure on the hemodynamic response to vasoconstrictors has not yet been examined. Intraluminal pressure is a primary determinant of vessel size and the force opposing vasoconstriction. Accordingly, we examined the effects of intraluminal pressure on the hemodynamic response to norepinephrine (NE)-induced vasoconstriction. METHODS AND RESULTS: In canine carotid arteries perfused with physiological salt solution, pressures at the proximal and distal ends of the artery, as well as flow, were continuously recorded. We altered intraluminal pressure using three diverse interventions: changes in perfusion pressure, decreasing distal resistance, and collaterals. In normal, nonstenotic arteries, NE decreased the external vessel diameter but did not reduce flow. Perfusion pressure changes did not affect the ED50 of the NE-diameter relation. After an intraluminal stenosis was created, NE-induced constriction decreased flow. The threshold concentration of NE needed to decrease flow decreased as the perfusion pressure decreased (38.5 +/- 17.9, 2.3 +/- 1.3, and 0.12 +/- 0.1 x 10(-7) mol/l for 125, 100, and 75 mm Hg of perfusion pressure, respectively; p less than 0.05). Lowering distal resistance decreased stenotic pressure and decreased the threshold NE concentration from 5.4 +/- 1.9 to 0.34 +/- 0.2 x 10(-7) mol/l (p less than 0.05), and increasing stenotic pressure with collaterals increased the threshold NE concentration from 2.6 +/- 1.4 to 7.5 +/- 4.6 x 10(-7) mol/l (p less than 0.05). CONCLUSIONS: In stenotic arteries, interventions that lowered the intraluminal pressure decreased the threshold NE concentration needed to decrease flow, and interventions that raised the intraluminal pressure increased the threshold NE concentration. This pressure-dependent constrictor sensitivity affects the vasomotor tone and is important in pathophysiology of ischemia occurring with hypotension (low perfusion pressure) or mild increase in myocardial oxygen demand (low distal arteriolar resistance). The results also suggest that collaterals, by maintaining stenotic pressure, could decrease the constrictor sensitivity and prevent ischemia. PMID- 1735164 TI - Changes in myocardial blood flow during development of and recovery from tachycardia-induced cardiomyopathy. AB - BACKGROUND: Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy and myocyte injury. Termination of SVT improves left ventricular (LV) function but is associated with LV hypertrophy. Changes in myocardial blood flow (MBF) that may accompany the development of and recovery from SVT cardiomyopathy might have a significant effect on LV function and myocyte structure. The goal of this study was to relate changes in LV function, myocyte composition, and coronary vascular structure to changes in MBF with the development and recovery of SVT cardiomyopathy. METHODS AND RESULTS: LV function and MBF were measured in three groups of conscious pigs: sham control (control; n = 8), after 3 weeks of atrial pacing (SVT, 240 beats per minute; n = 8), and after a 4-week recovery from SVT (post-SVT; n = 8) by echocardiography catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) rapid atrial pacing (240 beats per minute), and 3) during adenosine infusion (1.5 mumol/l.kg-1.min-1) without pacing. LV myocyte, capillary, and arteriole morphometric studies were performed in five additional pigs from each group using histochemistry and electron microscopy. LV fractional shortening was lower and left atrial pressure was significantly higher in the SVT group compared with control at rest, during pacing, and with adenosine (p less than 0.05). In the post-SVT group, fractional shortening returned to control values at rest and with adenosine, but fell from control values with pacing (p less than 0.05). Left atrial pressure fell in the post-SVT but remained significantly higher than control (p less than 0.05). LV/body weight ratio was significantly increased in the post-SVT group (p less than 0.05). In all states, SVT LVMBF was significantly reduced from control values (rest, 0.8 +/- 0.3 versus 1.6 +/- 0.3 ml-min-1.g-1; pacing, 1.2 +/- 0.2 versus 3.1 +/- 0.3 ml.min-1.g-1; adenosine, 1.4 +/- 0.3 versus 4.4 +/- 0.4 ml.min-1.g-1, respectively, p less than 0.05). In the post-SVT group, LVMBF was similar to control at rest (1.3 +/- 0.2 ml.min-1.g-1) but was significantly lower than control with pacing and adenosine (2.0 +/- 0.4 and 2.5 +/- 0.5 ml.min-1.g-1, respectively, p less than 0.05). Myofibrillar content fell significantly with SVT compared with control (42 +/- 5 versus 61 +/- 3%, p less than 0.05) and returned to control values in the post SVT group (64 +/- 3%). Capillary density remained unchanged in the SVT and post SVT groups, but capillary luminal diameter decreased and arteriole diameter increased in the SVT group (p less than 0.05). CONCLUSIONS: The LV dysfunction and myocyte injury with SVT cardiomyopathy were associated with reduced MBF. Early recovery from SVT cardiomyopathy resulted in hypertrophy with normal MBF at rest, but significantly reduced coronary reserve. PMID- 1735165 TI - In vivo relation of intramyocardial blood volume to myocardial perfusion. Evidence supporting microvascular site for autoregulation. AB - BACKGROUND: The goal of this study was to explore the role of several factors that affect intramyocardial blood volume by using minimally invasive computed tomography. Anesthetized dogs were scanned with the dynamic spatial reconstructor, a high-speed tomographic scanner, during injection of a bolus of iohexol into the aortic root. METHODS AND RESULTS: In control dogs, it is indicated that the fraction of myocardium that is blood (FMB, %) relates to myocardial perfusion (F, milliliters per gram per minute) in that region as FMB congruent to a.F1/2, where a = 9.5 +/- 1.2% (milliliters times minute per gram)1/2 (mean +/- SD) in the subendocardium and a = 9.6 +/- 1.1% in the subepicardium. In another group of dogs, for the myocardium perfused by a stenosed epicardial artery, a increased to approximately 10 for a 25-43% stenosis (or pressure gradient of 9 mm Hg across narrowing) and to greater than 11 for a 50-55% stenosis (or pressure gradient of 40 mm Hg across narrowing). In these dogs, flow was not impaired under control hemodynamic conditions, but the usual increase of flow (i.e., flow reserve) observed under maximum vasodilation conditions was impaired. In another group of dogs, progressive embolization (using 15-microns-diameter microspheres) of the left ventricular myocardial microcirculation caused the value of a to remain at approximately 9.5 with embolization up to 50% of the fatal dose of microspheres, but it then decreased progressively with embolization to 4.6 at the fatal dose. CONCLUSIONS: We conclude that the FMB/F relation reflects hemodynamic conductance at the microvascular level. PMID- 1735166 TI - Imaging the rejecting heart. In vivo detection of major histocompatibility complex class II antigen induction. AB - BACKGROUND: Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. METHODS AND RESULTS: Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. CONCLUSIONS: We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection. PMID- 1735167 TI - Programmed electrical stimulation and drugs identify two subgroups of ventricular tachycardias occurring 16-24 hours after occlusion of the left anterior descending artery. AB - BACKGROUND: Spontaneous sustained ventricular tachycardia (VT) occurring 16-24 hours after left anterior descending (LAD) coronary artery occlusion in the canine heart is most likely based on abnormal automaticity. In vitro, it has been demonstrated that the rate of the arrhythmia and the effect of overdrive pacing depends on the maximal diastolic potential (MDP). The MDP is also of importance in understanding the effect of antiarrhythmic drugs. To study 1) the possible presence of different responses to overdrive pacing and 2) the relation between the response to overdrive pacing and the effect of different antiarrhythmic drugs in the intact heart, we investigated the effect of 1) (prolonged) pacing and 2) lidocaine (3 mg/kg), verapamil (0.4-1.0 mg/kg), or flunarizine (2 mg/kg) during VT. METHODS AND RESULTS: In 21 conscious dogs with chronic atrioventricular block, 60 sustained VTs were observed 1 day after LAD occlusion. During VT, pacing with interstimulus intervals of 400, 300, and 200 msec for 15, 60, and 120 seconds was done on 40 VTs. Based on their response to pacing, VTs were divided into a pacing-suppressible (PS group) and a pacing-nonsuppressible group (PNS group). The mean cycle length in the PS group was significantly longer (410 +/- 50 msec) than in the PNS group (360 +/- 35 msec, p less than or equal to 0.01). Suppression was directly related to the rate and duration of pacing. Spontaneous recurrence of VTs was observed after 26 +/- 45 seconds. Lidocaine and verapamil increased cycle length of the suppressible VTs and terminated them, whereas flunarizine had no effect. Except for verapamil, which increased cycle length of the VTs, no effects were seen in the PNS group. CONCLUSIONS: In conscious dogs showing sustained VTs 16-24 hours after LAD occlusion, 1) the slower VTs can be suppressed by pacing, verapamil, and lidocaine but not by flunarizine, and 2) the faster VTs are not affected by pacing, lidocaine, and flunarizine, and are only slowed by verapamil. These findings are compatible with in vitro findings of abnormal automaticity, with the slower VTs originating from a higher MDP than the faster VTs. PMID- 1735168 TI - Percutaneous delivery of low-level laser energy reverses histamine-induced spasm in atherosclerotic Yucatan microswine. AB - BACKGROUND: Previous in vitro experiments performed in our laboratory have shown that low-level laser energy may produce prompt reduction in isometric tension of vascular smooth muscle. The present study was designed to extend these previous in vitro findings to an in vivo model and thereby investigate the hypothesis that laser light delivered percutaneously in vivo could successfully reverse arterial spasm. METHODS AND RESULTS: Spasm defined as greater than 50% reversible reduction in luminal diameter persisting for greater than or equal to 5 minutes was successfully provoked by injection of histamine (100-400 micrograms/kg) in 13 arteries among 10 atherosclerotic Yucatan microswine; the magnitude of histamine induced vasoconstriction was then documented angiographically by repeated injections of contrast media for as long as 30 minutes (controls). After return of angiographic luminal diameter to baseline, spasm was reproduced with a second injection of histamine into the same artery. Representative wavelengths generated by ultraviolet (UV), visible, and infrared lasers were then delivered percutaneously via conventional fiberoptics to the site of spasm, and angiographic assessment was repeated for as long as 30 minutes (treatment trial). In three arteries treated with UV (351 nm) light from an excimer laser, angiographic luminal diameter narrowing decreased from 100% to 23.9%, 50.0% to 9.3%, and 76.0% to 42.3%, respectively. The magnitude of laser-induced increase in luminal diameter was 50.2 +/- 22.7%, which was significantly greater than the magnitude of relaxation observed spontaneously during the control trials (10.9 +/ 9.8%, p = 0.02). Visible light from a helium-neon (632 nm) laser accomplished complete reversal of histamine-induced spasm in two of four arteries; in the remaining two arteries, luminal diameter narrowing percentages were reduced from 57.0% to 20.0% and from 76.5% to 30.8%, respectively. The magnitude of helium neon laser-induced relaxation (55.8 +/- 17.9%) was again significantly greater than that observed during the control trials (0.9 +/- 1.9%, p = 0.01). Finally, infrared irradiation from a diode-pumped neodymium:yttrium aluminum garnet (1,064 nm) laser decreased histamine-induced luminal diameter narrowing in three arteries from 100% to 21.4%, 56.0% to 8.7%, and 68.3% to 35.3%, respectively. The magnitude of infrared laser-induced improvement in luminal diameter narrowing was 53.0 +/- 23.3%, which was significantly greater than that observed during the control trials (12.9 +/- 10.7%, p = 0.01). In three additional arteries, fiberoptic sham trials (without laser irradiation) failed to produce relaxation of histamine-induced spasm. CONCLUSIONS: These findings document for the first time that light-induced relaxation of vascular smooth muscle, previously documented in vitro, may be reproduced in vivo. PMID- 1735169 TI - Heat shock protein induction in rat hearts. A role for improved myocardial salvage after ischemia and reperfusion? AB - BACKGROUND: To test the hypothesis that the heat shock response is associated with improved myocardial salvage after myocardial ischemia and reperfusion, rats treated with prior whole-body hyperthermia and 24 hours of recovery (n = 26) or 20 minutes of ischemic pretreatment and 8 hours of recovery (n = 24) and control rats (n = 27, n = 24, for hyperthermic and ischemic pretreatment, respectively) were subjected to 35 minutes of left coronary artery (LCA) occlusion and 120 minutes of reperfusion. METHODS AND RESULTS: Although ventricular samples from rats subjected to either hyperthermia (n = 7) or ischemic pretreatment (n = 6) all showed induction of HSP72 (heat shock protein), Western blot analysis revealed significantly greater amounts of HSP72 in samples obtained from rats subjected to hyperthermia compared with those from rats subjected to ischemic pretreatment. Control rats (n = 7) showed no significant presence of myocardial HSP72. After 35 minutes of LCA occlusion and 2 hours of reperfusion, infarct size was significantly reduced in heat-shocked rats compared with controls (8.4 +/- 1.7%, n = 26 versus 15.5 +/- 1.9%, n = 27; p = 0.007; mean +/- SEM; infarct mass/left ventricular mass x 100). There were no significant differences in left ventricular (LV) systolic pressure, heart rate, LV dP/dt, or rate-pressure product between heat-shocked (n = 11) and control (n = 14) rats during the ischemic period. There were no differences in infarct size between ischemically pretreated and control rats subjected to 35 minutes of ischemia and reperfusion (9.7 +/- 2.1%, n = 23 versus 10.0 +/- 2.1, n = 24; p = NS). CONCLUSIONS: In this model of ischemia and reperfusion, prior heat shock was associated with significantly improved myocardial salvage after 35 minutes of LCA occlusion and reperfusion. This improved salvage was correlated with marked HSP72 induction and was independent of the hemodynamic determinants of myocardial oxygen supply and myocardial oxygen demand during the ischemic period. In contrast, mild HSP72 induction by ischemic pretreatment was not associated with improved myocardial salvage after myocardial ischemia and reperfusion. Thus, the absolute levels of HSP72 may be important in conferring protection from ischemic injury in this animal model. PMID- 1735170 TI - Coronary cyclic flow variations "precondition" ischemic myocardium. AB - BACKGROUND: Repeated brief episodes of myocardial ischemia performed by mechanical clamping of a coronary artery "precondition" the heart and reduce infarct size after a subsequent sustained ischemia. It is not known, however, whether spontaneous episodes of transient ischemia caused by formation of platelet thrombi, which may occur in unstable angina, have a similar cardioprotective effect. METHODS AND RESULTS: Therefore, our objective was to determine whether brief spontaneous thrombotic episodes of ischemia/reperfusion could limit infarct size and preserve contractile function following 60 minutes (protocol 1) or 90 minutes (protocol 2) of sustained ischemia and 4-4.5 hours of reperfusion in the canine model. Before the sustained coronary occlusion, dogs underwent a 30-minute "treatment" period consisting of: no intervention (control group), four repeated episodes of 3-minute mechanical occlusion plus 5-minute reperfusion (preconditioned group), or coronary artery stenosis and endothelial injury, resulting in a mean of four spontaneous episodes of cyclic flow variations (CFV group) caused by formation and dislodgment of platelet thrombi. In protocol 1 (60-minute sustained ischemia plus 4.5-hour reperfusion), infarct size was significantly smaller in both the preconditioned and CFV groups compared with controls (3.5 +/- 1.4%,* 3.4 +/- 2.1%,* and 9.9 +/- 2.7% of the myocardium at risk, respectively; *p less than 0.05 versus control). In contrast, neither preconditioning nor CFV preserved contractile function: Segment shortening during sustained occlusion was equally depressed at -15% to -20% of baseline values among the three groups and equally stunned at +12% to +18% of baseline during the 4.5 hours of reflow. In protocol 2 (90-minute sustained ischemia plus 4-hour reperfusion), only CFV continued to exert a cardioprotective effect: Infarct size averaged 15.0 +/- 4.1%, 7.4 +/- 2.5%,* and 16.5 +/- 4.4% of the region at risk in the preconditioned, CFV, and control groups, respectively (*p less than 0.05 versus control). Contractile function, however, was similar among all three groups both during 90 minutes of sustained occlusion and throughout 4 hours of reperfusion. CONCLUSIONS: We therefore conclude that repeated coronary thrombus formation preconditions the ischemic myocardium: In fact, in contrast to mechanical preconditioning, cardioprotection provided by CFV persisted following 90 minutes of sustained coronary occlusion. However, preconditioning by thrombotic or mechanical occlusion neither preserved myocardial contractile function during sustained coronary occlusion nor prevented stunning after reperfusion. These data raise the possibility that clinical episodes of unstable angina prior to acute myocardial infarction may precondition the ischemic myocardium. PMID- 1735171 TI - Conjunctive enhancement of enzymatic thrombolysis and prevention of thrombotic reocclusion with the selective factor Xa inhibitor, tick anticoagulant peptide. Comparison to hirudin and heparin in a canine model of acute coronary artery thrombosis. AB - BACKGROUND: Effective thrombolytic recanalization of an occluded coronary vessel is often limited by acute thrombotic reocclusion, which has galvanized the search for effective adjunctive or conjunctive antithrombotic agents. METHODS AND RESULTS: Recombinant versions of tick anticoagulant peptide (rTAP) and hirudin (rHIR) are highly selective and potent polypeptide inhibitors of factor Xa and thrombin, respectively. The comparative antithrombotic efficacies of rTAP, rHIR, and heparin, administered conjunctively with recombinant tissue-type plasminogen activator (rt-PA), on thrombolytic reperfusion and reocclusion, were determined in a canine model of occlusive coronary artery thrombosis with a superimposed critical stenosis. In this model, a platelet-rich occlusive thrombus was formed after damage to the intimal surface of the left circumflex coronary artery induced by electrolytic injury. Fifteen minutes after occlusion, the dogs received a systemic intravenous administration of either saline (control), heparin (200 units/kg bolus + 2 units/kg/min, heparin (HEP) 200 or 100 units/kg bolus + 1 unit/kg/min, HEP 100), rHIR (50 or 100 micrograms/kg/min, rHIR 50 or 100, respectively), or rTAP (100 micrograms/kg/min, rTAP 100) followed 15 minutes later by rt-PA (100 micrograms/kg bolus + 10 micrograms/kg/min over 90 minutes). Infusions of the conjunctive agents were discontinued 60 minutes after termination of rt-PA. The incidence and time (mean +/- SEM) to thrombolytic reperfusion were determined for control (five of 12; 68.0 +/- 7.8 minutes), HEP 100 (six of eight; 40.1 +/- 8.3 minutes), HEP 200 (six of eight; 39.8 +/- 9.5 minutes), rHIR 50 (six of eight; 51.7 +/- 14.6 minutes), rHIR 100 (eight of eight; 19.5 +/- 4.2 minutes), and rTAP 100 (eight of eight; 22.8 +/- 10.0 minutes). The incidence and time to reocclusion after rt-PA were determined for control (four of five; 45.7 +/- 12.5 minutes), HEP 100 (four of six; 18.2 +/- 10.7 minutes), HEP 200 (five of six; 26.2 +/- 20.7 minutes), rHIR 50 (four of six; 47.3 +/- 21.6 minutes), rHIR 100 (six of eight; 89.8 +/- 5.9 minutes), and rTAP 100 (three of eight; 54.0 +/- 16.3 minutes). All of the dogs that reoccluded in the rHIR 100 group did so after termination of the inhibitor infusion, whereas two of the three dogs in the rTAP 100 group that reoccluded did so during the inhibitor infusion. Coronary artery blood flow was characterized by intermittent periods of reocclusion and recanalization in all groups except rTAP 100. CONCLUSIONS: The potent antithrombotic effects of rTAP in this model directly implicate de novo thrombin formation as a major source of thrombin activity within the highly thrombogenic residual thrombus. These findings suggest that direct inhibition of prothrombinase activity may be an effective strategy in the development of a new class of conjunctive agents. PMID- 1735172 TI - Mechanism of global functional recovery despite sustained postischemic regional stunning. AB - BACKGROUND: The mechanisms whereby reperfusion of a 20-minute coronary occlusion result in global functional recovery despite persistent regional dysfunction were studied in 11 open-chest reflex-blocked dogs. METHODS AND RESULTS: Pressure volume and pressure-thickness relations were simultaneously determined before, during, and after reperfusion of left anterior descending artery (LAD) occlusion. Wall thickness was determined by sonomicrometry in both ischemic and remote regions. Chamber systolic function was assessed by end-systolic pressure-volume relations (ESPVR) obtained by conductance catheter and defined by a slope (Ees) and volume shift at a common end-systolic pressure (delta Ves). LAD occlusion produced regional systolic thinning (-7 +/- 6%) and global left ventricular dysfunction (ESPVR shifted rightward (delta Ves = +8.6 +/- 5.1 ml, p less than 0.001) with no Ees change). After nearly 1 hour of reperfusion, LAD region thickening remained markedly reduced at 4 +/- 7% (versus 23 +/- 8%, control), yet chamber systolic function fully recovered (ESPVR shifted back leftward delta Ves = -8.9 +/- 6.5 ml). Ischemia induced a leftward shift and systolic thinning of LAD region pressure-thickness relations. Reperfusion returned end-systolic pressure-thickness relations halfway to their control position and diastolic relations fully to control position. This was primarily due to increased passive stiffening in about half the hearts and a partial return of active function in the remaining ones. The net effect was to eliminate systolic thinning over a physiological loading range, thus normalizing chamber systolic performance. Reflex activation, remote hyperfunction, or altered chamber loading did not account for the postreperfusion disparity between global and regional function. CONCLUSIONS: These data suggest a mechanism to account for greater functional benefits of reperfusion beyond that anticipated from regional wall motion analysis. PMID- 1735173 TI - Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium. AB - BACKGROUND: Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates). METHODS AND RESULTS: In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15 minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/ 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate. CONCLUSIONS: These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow. PMID- 1735174 TI - TIMI IIB follow-up. Lessons for clinicians and investigators. PMID- 1735175 TI - Vascular biology and invasive cardiology. The streams are beginning to merge. PMID- 1735176 TI - Prevalence, circumstances, mechanisms, and risk stratification of sudden cardiac death in artificial ventricular pacing. PMID- 1735177 TI - Myocardial preconditioning. Part of the adenosine revival. PMID- 1735178 TI - Pathogenesis of edema in constrictive pericarditis. PMID- 1735179 TI - Report of the Task Force on the Availability of Cardiovascular Drugs to the Medically Indigent. PMID- 1735180 TI - Cryoglobulins and the immunopathological manifestations of autoimmune disease. PMID- 1735181 TI - Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with rheumatic diseases. AB - The neuroendocrine polypeptide hormone beta-endorphin (beta-END), which is released from various tissues including the anterior pituitary gland and cells of the immune system, has recently been implicated as having an immunoregulatory role. We used a radioimmunoassay to measure beta-END levels in circulating mononuclear leucocytes from normal subjects and patients with various rheumatic diseases. Levels of beta-END in leucocytes from patients were lower than in leucocytes from healthy subjects (P less than 0.001). Whereas levels of beta-END in leucocytes from patients with the various rheumatic disorders were not significantly different, an inverse correlation was found between beta-END levels in leucocytes and expression of rheumatoid factor (P less than 0.025) and erythrocyte sedimentation rate (P less than 0.025). This study demonstrates decreased content of beta-END in cells of the immune system related to parameters of inflammatory activity in rheumatic diseases. PMID- 1735182 TI - Rheumatoid factors in mice bearing the lpr or gld mutation. Selective production of rheumatoid factor cryoglobulins in MRL/MPJ-lpr/lpr mice. PMID- 1735183 TI - Flare-up of experimental arthritis in mice with murine recombinant IL-1. AB - Intra-articular injections of murine recombinant IL-1 (mrIL-1) during the chronic phase of antigen-induced arthritis (AIA) induced a flare-up of the smouldering inflammation. The exacerbation was characterized by acute and transient joint swelling and this coincided with the extravascular accumulation of neutrophils. IL-1 injected into arthritic joints of neutropenic mice demonstrated that joint swelling was independent of the neutrophil influx into the joint. Both phenomena were absent when IL-1 was injected into a naive joint. The IL-1-induced flare-up was not T cell mediated as in the antigen-induced flare-up, and suggestive evidence is presented that IL-1 sensitivity depended on the resident macrophage population. This explained why the hypersensitivity is not restricted to the immunologically mediated arthritis but reflects a more general hypersensitivity of previously injured joints, e.g. zymosan-induced arthritis and IL-1-affected joints. In addition, IL-1 could also potentiate the antigen-specific flare-up of chronic AIA and prolongs the duration of the exacerbation. Our data indicate that joints bearing a chronic infiltrate are at risk from exacerbations in two ways: a T cell mediated rechallenge with antigen, and a non-specific reactivation by systemic and local IL-1 generation. PMID- 1735184 TI - Quantitative studies of monoclonal antibody 5-1-6-induced proteinuric state in rats. AB - Murine monoclonal antibody (MoAb) 5-1-6 was already reported to bind to epithelial cell foot processes and to cause proteinuria in rats. In vivo kinetics of the injected MoAb 5-1-6, relationship between the quantity of kidney-binding antibody and proteinuria, and changes in the amount of antigenic molecule recognized by this MoAb in the proteinuric state were studied. The amount of total kidney-binding antibody (TKAb) as determined 1 h after a 2 mg administration was 50.8 +/- 10.4 micrograms/2 kidneys, and TKAb declined to 1.9 +/- 0.4 at day 15. The minimum dose of MoAb required to induce proteinuria was 125 micrograms as the injected dose. This dose corresponded to 12.8 micrograms of TKAb at 1 h and 0.34 micrograms of TKAb at day 5. The amount of MoAb 5-1-6 binding to isolated normal glomeruli was also shown to exceed 147.7 micrograms/76,000 glomeruli, indicating proteinuria to be induced provided more than 8.7% (= 12.8/147.7) of the critical epitopes is specifically occupied by MoAb. The total amount of MoAb 5-1-6 bound to glomeruli in vivo and in vitro was assayed with [125I]-labelled anti-mouse IgG. The amount of [125I] anti-mouse IgG bound to glomeruli was 6.93 +/- 0.45 micrograms/10,000 glomeruli from rat 5 days after this MoAb injection and 26.58 +/- 0.66 micrograms/10,000 control glomeruli, indicating the decrease in the number of MoAb 5-1-6-recognized antigen molecules in glomeruli isolated from the rat in proteinuric state induced by this MoAb. Thus, the MoAb 5-1-6-recognized molecule itself may principally function to regulate the permeability of the glomerular capillary wall and the decrease of the molecule may lead to proteinuria. PMID- 1735185 TI - Thymus lymphocytes in uraemic rats and the effect of thymosin fraction 5 in vivo. AB - Thymus lymphocyte subsets in uraemic rats were studied using monoclonal antibodies. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the weight of the thymus decreased in uraemic rats. As for lymphocyte subsets, the frequency of W3/25+OX8+ decreased and those of W3/25-OX8-, W3/25+OX8- and W3/25- OX8+ relatively increased in uraemic rats. All these changes were more significant in severely uraemic than in moderately uraemic rats. When thymosin fraction 5 (TF5) was administered to severely uraemic rats, the weight of the thymus increased and the lymphocytes subsets normalized. These results suggest that uraemia may cause a maturational impairment of thymus lymphocytes by the depression of thymic hormone secretion. PMID- 1735186 TI - Mucosal cell-mediated immunity to mycobacterial, enterobacterial and other microbial antigens in inflammatory bowel disease. AB - Culture studies have suggested that Mycobacterium paratuberculosis may play a role in the aetiology of Crohn's disease. However, evidence of sensitization to mycobacterial antigens amongst patients with Crohn's disease has not yet been adequately demonstrated. Previous studies of cell-mediated immunity (CMI) in Crohn's disease were restricted to responses of peripheral blood mononuclear cells (PBMC) to mycobacterial antigens. In this study we have investigated the proliferative responses of both PBMC and mesenteric lymph node mononuclear cells (MLNMC) to a range of mycobacterial and non-mycobacterial antigens. There was no evidence of specific sensitization in the responses of MLNMC and PBMC from patients with inflammatory bowel disease (IBD) to the mycobacterial antigens. However, anergy to M. paratuberculosis could not be excluded. IBD MLNMC responses to most antigens were generally greater than those of PBMC, which were often undetectable. When compared with controls, there was evidence of increased CMI to a range of non-mycobacterial antigens, especially Yersinia enterocolitica, amongst both MLNMC and PBMC from patients with Crohn's disease and ulcerative colitis (UC). These results do not provide support to the proposed role of mycobacteria in the pathogenesis of Crohn's disease, but indicate that further investigation may determine a role for bacterial-specific T cell-mediated responses in the pathogenesis of IBD. PMID- 1735187 TI - Subclass composition and J-chain expression of the 'compensatory' gastrointestinal IgG cell population in selective IgA deficiency. AB - The subclass distribution of IgG-producing immunocytes was examined by two-colour immunohistochemistry in gastrointestinal mucosa of 14 patients with selective serum IgA deficiency providing the following biopsy material: gastric (n = 1); jejunal (n = 12); colonic (n = 1); and rectal (n = 2). All except two patients suffered from various infections, and coeliac disease was observed in six of them. Control reference data were based on biopsies from immunologically intact subjects, including histologically normal jejunal (n = 10) and large bowel (n = 10) mucosa and stomach mucosa with slight chronic gastritis (n = 8). The total mucosal population of immunoglobulin-producing cells per 500 microns gut length unit was only slightly decreased in IgA deficiency because of an increased number of IgG (30%) and especially IgM (71%) immunocytes. The IgG1 immunocyte proportion in the proximal gut (median 87%) was higher than that in the comparable controls (gastric 69%, jejunal 66%). A similar trend was seen in the distal gut (69%) compared with controls from the large bowel mucosa (55%). Conversely, IgG2 and IgG3 cell proportions were significantly decreased compared with the respective controls from the proximal gut. The same was true for IgG4, which also was significantly reduced in jejunal mucosa. Paired staining for cytoplasmic J chain and immunoglobulin isotype showed 71% positivity for jejunal IgG-producing cells in IgA deficiency, which was somewhat reduced compared with comparable controls (89%). J chain appeared to be preferentially expressed by IgG1 cells (75%), but was also found in IgG2 (70%), IgG3 (32%) and IgG4 cells (33%). IgM-producing cells showed a J-chain positivity (99%) in IgA deficiency similar to normal (100%). Our results suggested that the block in mucosal B cell differentiation to IgA expression in the proximal gut is mainly located immediately upstream to the CH alpha 1 gene, giving excessive terminal maturation of J-chain-positive IgG1 immunocytes. PMID- 1735188 TI - Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy. AB - Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a AChR. PMID- 1735189 TI - Antibodies against C1q in anti-glomerular basement membrane nephritis. AB - The prevalence of antibodies against the collagen-like region of the subcomponent of the first component of complement, C1q, was investigated in 11 patients with anti-glomerular basement membrane (GBM) nephritis. Anti-C1q antibodies (anti C1qAb) were detected in seven patients. IgG anti-C1qAb were found in four and IgA anti-C1qAb in five patients. During follow up of the patients a relationship was observed between the levels of IgG anti-C1qAb and the levels of anti-GBM antibodies (anti-GBMAb). Gelfiltration experiments indicated that both IgG anti C1qAb as well as IgG anti-GBMAb were monomeric and that binding also occurred with the F(ab')2 fragments of the antibodies. Although anti-C1qAb and anti-GBMAb are both directed against a collagen-like structure, it was demonstrated by means of inhibition experiments that anti-C1qAb and anti-GBMAb are directed against different antigenic sites. Comparison of patients with anti-GBM nephritis with and without anti-C1qAb revealed that there were no differences in disease activity or disease severity. Therefore, the results of this study suggest that anti-C1qAb do not play a direct pathogenetic role in anti-GBM nephritis. PMID- 1735190 TI - The role of interferon-gamma in lymphocytic thyroiditis: its functional and pathological effect on human thyrocytes in culture. AB - Interferon-gamma (IFN-gamma) has been recognized to possess diverse non immunological effects on epithelial cells such as cellular growth and differentiation. We have previously demonstrated that IFN-gamma suppressed thyroid-stimulating hormone (TSH)-stimulated thyroglobulin (TG) synthesis in human thyrocytes through inhibition of TG gene transcription. To define the pathological mechanism involved in the action of IFN-gamma, we studied the ultrastructural changes of human thyrocytes cultured in monolayer. Stimulation of the thyrocytes with TSH 10 mU/ml for 2 days resulted in marked increase in TG release into the medium. This was accompanied by elongation of microvilli, increase in follicles and acinar formation, increase in secretory granules and prominence of Golgi apparatus and rough-surfaced endoplasmic reticulum. Addition of IFN-gamma (500 U/ml) resulted in marked degeneration with shrinkage of the cell membrane, vacuolation of cytoplasm, swollen mitochondria and presence of lysosomal granules. Co-culturing the thyrocytes with the IFN-gamma and TSH resulted in suppression of the morphological responsiveness to TSH. There was also suppression of TSH-induced TG secretion. However, at 500 U/ml IFN-gamma did not cause lysis of the thyrocytes as estimated by the cellular DNA content. Furthermore, binucleated cells were frequently encountered in those wells that were treated with IFN-gamma for either 2 or 5 days. The findings suggest that IFN gamma resulted in de-differentiation and degeneration of the thyrocytes, which subsequently regained the growth potential and showed attempts at regeneration. This may explain why most patients with lymphocytic thyroiditis recover from the acute injury and do not suffer from permanent hypothyroidism. PMID- 1735191 TI - Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy. AB - Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma. PMID- 1735192 TI - Antigenic specificity and subset analysis of T cells isolated from the bronchoalveolar lavage and pleural effusion of patients with lung disease. AB - Cellular infiltrates of bronchoalveolar lavage (BAL) and pleural effusion from patients with tuberculosis (TB) and lung cancer were characterized for the presence of different T cell subsets by phenotypic analysis. The specificity of the T cells for mycobacterial antigens was then compared for the two disease compartments. The composition of T cell subsets within the BAL, in contrast to pleural effusion cells (PEC), revealed evidence of sequestration of CD8+ cells. BAL T cells were found to be a predominantly CD29+ DR+ memory population of activated cells. Although polyclonal populations of BAL T cells proliferated poorly to Mycobacterium tuberculosis antigens, mycobacterial antigen-reactive monoclonal T cell populations could be derived from the alveolar compartment. Two clones were shown to recognize the 65-kD heat shock protein of mycobacteria, and one of these clones recognized a conserved sequence of the molecule. Several BAL derived clones, responding to a mycobacterial soluble extract, did not, however, recognize purified mycobacterial antigens, previously identified as highly stimulatory for PEC-derived T cells. T cell clones, derived from PEC of two TB patients, responded to the 38-kD and 71-kD, as well as the 65-kD mycobacterial antigens. Examination of the activation requirements of BAL-derived T cell clones, specific for mycobacterial antigens, revealed that exogenous IL-2 was necessary for the T cells to sustain proliferation. This was in contrast to the mycobacterial antigen-reactive T cells cloned from PEC. These results suggest that T cell populations with distinct antigen specificities and activation requirements are present in BAL and PEC. PMID- 1735193 TI - Soluble IL-2 receptor and tumour necrosis factor-alpha in plasma of haemophilia patients infected with HIV. AB - We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL 2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV seropositive to AIDS/ARC. PMID- 1735194 TI - Phagocytosis of Giardia lamblia trophozoites by cytokine-activated macrophages. AB - Phagocytosis of Giardia lamblia trophozoites by cytokine-activated and non activated bone marrow-derived macrophages was examined in vitro. Macrophages treated with recombinant interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages. Maximal uptake of parasites occurred after 4 h and 6 h of incubation where 81.4% and 79.1% of macrophages were positive for trophozoites. Other cytokines tested, IL-2, IL-3, IL-4, IL-5, GM CSF, CSF-1 and tumour necrosis factor-alpha (TNF-alpha) either alone or in combination with LPS, failed to activate macrophages to phagocytose G. lamblia. The induction of this activated macrophage anti-microbial function was achieved pharmacologically using phorbol myristate acetate (PMA) and ionophore A23187. The giardicidal activity of macrophages activated with IFN-gamma and LPS or that induced by PMA and A23187 was inhibited by H-7, indicating the role for protein kinase C in the intracellular events following activation. PMID- 1735195 TI - Anti-P30 IgA antibodies as prenatal markers of congenital toxoplasma infection. AB - This study extends a previous study and confirms that the detection of anti-P30 IgA antibodies is very helpful in the diagnosis of acute acquired or congenital toxoplasmosis. Moreover, we demonstrate that an anti-P30 IgA response can be mounted in the fetuses infected by Toxoplasma gondii during their intra-uterine life as early as week 23 of gestation. A double-sandwich ELISA described in our previous work was used to detect anti-P30 IgA antibodies in 1378 human serum samples collected from 551 patients, including 162 fetuses whose mothers had been infected by T. gondii during pregnancy, 46 congenitally infected and 90 uninfected newborns and 253 women suspected of having been infected during pregnancy, including the mothers of fetuses and newborns previously described. Anti-P30 IgA antibodies were detected in all cases of acute toxoplasmosis but in no case of chronic toxoplasmosis: in the majority of cases, the IgA antibody titre fell below cut-off in 3-9 months. Among the 46 congenitally infected newborns, anti-P30 IgA antibodies were detected in sera of 41 infected newborns (38 at birth, two in the first months of life, one in the seventh month of life), while anti-P30 IgM antibodies were detected in only 30 cases at birth and in one case during the first month of life. Among 162 fetuses, anti-P30 IgA response was observed in five infected fetuses, but was not detected in either 152 uninfected fetuses or in five fetuses considered as infected. The absence or presence of anti-P30 IgA antibodies in the fetus is discussed in relation to the date of maternal infection and collection of the fetal blood. It clearly appears from our study that the combined testing of both IgM and IgA in the fetus and the newborn is essential for a more efficient diagnosis of infection. PMID- 1735196 TI - Involvement of HLA class II molecules in acquisition of staphylococcal enterotoxin A-binding activity and accessory cell activity in activation of human T cells by related toxins in vascular endothelial cells. AB - Human umbilical vascular endothelial cells (HUVEC) express HLA class II molecules upon stimulation with recombinant human interferon-gamma (IFN-gamma). Staphylococcal enterotoxin (SE) A (SEA)-binding assay using [125I]-SEA showed the presence of specific SEA binding in HUVEC stimulated with IFN-gamma but not in unstimulated HUVEC. Levels of HLA class II expression and SEA-binding increased as the IFN-gamma concentration and the period of stimulation were increased. Binding of [125I]-SEA to the IFN-gamma-stimulated HUVEC was reduced markedly by an anti-DR/DP MoAb. T cells produced IL-2 upon stimulation with a group of SEs (SEA, SEB, SEC, SED and SEE) in the presence HUVEC stimulated with IFN-gamma but not in the presence of control HUVEC. The level of accessory cell activity in the IFN-gamma-stimulated HUVEC was related to the level of HLA class II expression and SEA-binding activity. Antibodies to HLA class II molecules almost completely inhibited the response. These results indicate that HLA class II molecules are directly involved in the acquisition of these activities in HUVEC. PMID- 1735197 TI - The distal radioulnar joint. Symposium. PMID- 1735198 TI - Distal radioulnar joint arthroplasty. Current concepts. AB - Arthroplasty techniques for the distal radioulnar joint can be grouped into several categories. These are resectional or excisional arthroplasty, hemiresection or partial resectional arthroplasty, ulnar shortening, or replacement arthroplasty. These techniques are used in varying conditions and situations. Once the function of the radioulnar joint is understood, the choice of arthroplasty technique is simplified. This article presents the theoretical basis for selecting a particular type of arthroplasty technique in any patient. The author's hemiresection interposition technique of arthroplasty developed in the mid 1970s. Sufficient results have now been published that an assessment of the efficacy of the procedure is available. The author's current concept is that detailed and increasing experience with the procedure has uncovered some problems and some modifications. The major indications for the hemiresections arthroplasty and its alternatives must be in the armamentarium of those dealing with this joint. PMID- 1735199 TI - The Sauve-Kapandji procedure. AB - In 1936, Sauve and Kapandji described a procedure that included an arthrodesis across the distal radioulnar joint and created a pseudarthrosis of the ulna, proximal to the fusion, to restore pronation and supination. The author has used this technique because preservation of the head of the ulna minimizes the potential for some of the complications that can follow its excision. Retention of the head of the ulna would secure a more normal transmission of loads across the wrist, maintain full support to the carpal condyle and to the extensor carpi ulnaris tendon, and preserve the normal contour and appearance of the wrist. This paper presents the author's experience using this procedure in 37 wrists with rheumatoid arthritis, osteoarthrosis and posttraumatic changes of the distal radioulnar joint, and chondromalacia of the head of the ulna. This is a satisfactory operation, although not infallible. It is probably contraindicated when treating the unstable or frankly subluxed or dislocated distal radioulnar joint, ulna dorsal, a therapeutic problem for which there is no reliable solution. Indications for the Sauve-Kapandji technique are discussed in relation to other operations frequently used for the distal radioulnar joint. PMID- 1735200 TI - The "wafer" procedure. Partial distal ulnar resection. AB - A technique of partial resection of the distal ulna ("wafer" procedure) for the treatment of patients with symptomatic tears of the triangular fibrocartilage complex or mild ulnar impaction syndrome or both is described. The distal 2-4 mm of the distal ulna is resected while preserving the distal radioulnar joint and the styloid process of the ulna and the ligaments attached to it. The triangular fibrocartilage can be debrided, repaired, or partially excised. The wafer procedure has several advantages and avoids some of the potential complications of other treatment methods. PMID- 1735201 TI - Stabilization of the distal ulna by transfer of the pronator quadratus origin. AB - Surgical and nonsurgical treatment of distal radioulnar joint instability has characteristically been unsatisfactory. This present paper presents a surgical method involving the removal and transfer of the origin of the pronator quadratus to a more dorsal position, which effectively gives a dynamic stabilization to the joint. Temporary internal immobilization is performed with a transverse Kirschner wire that is removed at four weeks, and graded physical therapy is started at that time. PMID- 1735202 TI - Bone-fibrin mixture in spinal surgery. AB - When bone grafting is performed adjacent to the spinal cord, instability of the grafted bone can result in compression of the spinal cord. To prevent this complication, fibrin sealant was mixed with the fine fragments of autogeneic bone, and the resultant pastelike mixture was used as a graft material. Operative procedures performed were posterolateral fusion (11 cases), anterior fusion (seven cases), and grafting into the bone defect (one case). After solidification of fibrin sealant, the autogeneic bone grafts were found to be firmly fixed in place, resulting in good bony fusion, and there were none of the neurologic symptoms associated with graft instability. No neurotoxicity was observed in any of these patients. Fibrin sealant was found to be an effective material for spinal surgery. PMID- 1735203 TI - Anatomy of the distal radioulnar joint. AB - The distal radioulnar joint (DRUJ) is of the utmost importance in treatment of fractures of the distal radius. To improve the treatment of these fractures, knowledge of the anatomy and biomechanics of the DRUJ is essential. Three major findings from anatomic specimen studies of the DRUJ are discussed. The radius of the curvature of the sigmoid notch is 4-7 mm larger than that of the ulnar head, and consequently pronation and supination are a combined rotation and sliding movement in the DRUJ. The ulnar head has an average inclination of 20 degrees relative to the long axis of the ulna. Being parallel to the ulnar head, the sigmoid notch of the radius should have the same inclination. In the DRUJ, stability supported by joint surface architecture is minimal, and the ligament is therefore of particular importance to the stability. PMID- 1735204 TI - Epidural compression in the spinal canal caused by excessive adipose tissue. A case report. AB - Excessive deposition of fat in the epidural space is rare. In a recent review of the literature, there were 15 reported cases, 14 were associated with steroid use and one was attributed to hypothyroidism. This report reviews treatment of a patient with symptoms of cauda equina compression caused by epidural adipose tissue. He had no history of steroid use or obvious evidence of an underlying endocrinopathy. PMID- 1735205 TI - Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava. AB - Clinical and ultrastructural study of four cases of Coffin-Lowry syndrome (CLS), a heritable disorder with peculiar facies, stooped posture, vertebral changes, and mental retardation, is reported. Three of the four cases had myelopathy caused by calcification of the ligamenta flava in early adulthood. These patients demonstrated that CLS is a calcium pyrophosphate dihydrate crystal deposition disease, and it is postulated that a metabolic abnormality in collagen and in proteoglycans are responsible for some aspects of CLS. PMID- 1735206 TI - Latissimus dorsi transfer for the treatment of irreparable tears of the rotator cuff. AB - Sixteen irreparable, massive rotator cuff tears were treated with latissimus dorsi transfer and reviewed after an average of 33 months. There were no neurovascular complications or infections. Pain relief was satisfactory in 94% of the shoulders at rest and in 81% on exertion. Flexion was 83 degrees preoperatively and 135 degrees postoperatively. The functional value of the shoulder averaged 73% of an age- and gender-adjusted normal score. For the 12 shoulders with a functional subscapularis, it averaged 82%; for those four without a functioning subscapularis, 48%. If the subscapularis was torn and could not be adequately repaired, latissimus dorsi transfer was of no value. In cases with good subscapularis function but irreparable defects in the external rotator tendons, restoration of approximately 80% of normal shoulder function was obtained, indicating that latissimus dorsi transfer is a safe and valuable alternative for the treatment of this specific type of irreparable rotator cuff tear. PMID- 1735207 TI - The Hitchcock procedure. A cause for failure: a case report. AB - A 40-year-old man with a tenodesis of the long head of the biceps brachii in the bicipital groove (Hitchcock's operation) for bicipital tendinitis had recurrence of pain seven months after the operation. Roentgenograms of the acromiohumeral interval, taken when the patient tensed the biceps brachii, showed significant upward migration of the humeral head with a decrease in the acromio-humeral interval on the operated side. The authors postulate that resection of the stabilizing, intraarticular segment of the long head of the biceps in the Hitchcock's procedure allowed the short head to draw the humeral head proximally, resulting in a decrease in the acromiohumeral interval and recurrence of impingement. This is one possible explanation for the poor long-term results of the Hitchcock procedure. PMID- 1735208 TI - Conservative treatment of rotator cuff tears. AB - Among 124 shoulders in 114 patients with complete rotator cuff tears who had been treated conservatively from 1980 until 1989, 62 shoulders in 54 patients were observed to identify the findings on initial examinations and correlate them with the final results. The follow-up period averaged 3.4 years. According to modified criteria of Wolfgang, 51 shoulders in 45 patients (82%) rates satisfactory (excellent or good). The overall scores of pain, motion, and function improved significantly. The results were less satisfactory in patients observed more than six years. The patients with satisfactory results (Group 1) and unsatisfactory results (Group 2) among those observed more than five years were compared. In Group 1, the scores of pain, motion, and strength improved significantly at follow-up examinations, whereas those of function did not. In Group 2, no improvement was recognized in any categories. The only significant differences in the initial findings between the two groups were the active abduction angle and the abduction strength: the patients in Group 1 retained a good range of motion and strength, whereas those with unsatisfactory results had a limited range and muscle weakness on first examinations. Conservative treatment affords satisfactory results when it is given to the patients with well-preserved motion and strength, although in some cases function may deteriorate with time. PMID- 1735209 TI - A histopathologic study of late aseptic loosening of cemented total hip prostheses. AB - Eighteen patients being treated for revision total hip arthroplasty for aseptic loosening an average of 9.5 years after primary cemented hip arthroplasty were studied. The patients were found to have been symptomatic an average of one year before revision. Review of the roentgenograms at the time of revision revealed that most patients had moderate to severe loosening of the prostheses by Charnley's criteria. These findings were confirmed at surgery. Study of the tissue surrounding the prostheses suggests that the prominent particles were methylmethacrylate "pearls" caused by cement fragmentation. These particles were surrounded by histiocytes that were actively synthesizing and releasing protein. Cement fragmentation and not polyethylene wear may be the major cause of late aseptic loosening of cemented hip prostheses. PMID- 1735210 TI - Evaluation of the hip with pigmented villonodular synovitis. A case report. AB - Pigmented villonodular synovitis (PVNS) is an uncommon disorder of the synovium that rarely involves the hip joint. The natural history of an untreated case of PVNS is presented herein. A young adult with a painful hip and destructive changes on plain roentgenograms requires further diagnostic evaluation. The relative value of current imaging techniques is discussed in this report. Plain roentgenograms alone often suggest the correct diagnosis of PVNS of the hip, but traditional criteria have proven to be inaccurate. Computed tomography (CT) is helpful in demonstrating the location and degree of bone loss throughout the pelvis and assists in determining the need for bone graft or prosthetic modification in preoperative planning. Experience with magnetic resonance imaging (MRI) in this disorder is limited, but no clear advantage over CT has been demonstrated thus far. Three-dimensional reconstruction has provided no useful information not already found on plain CT or MRI. For diagnostic accuracy and effective preoperative planning, evaluation should include a complete blood count, sedimentation rate, CT scan, and MRI. PMID- 1735211 TI - Torsional fixation of the femoral component in total hip arthroplasty. The effect of surgical press-fit technique. AB - Rotational loading of the femoral component has recently emerged as a prime factor for causing loosening and failure of total hip replacements. In this study the effect of surgical press-fit technique on torsional fixation of the femoral component was evaluated. The commonly used line-to-line reaming technique was compared to an underreaming technique using both four-fifths and one-third porous coated anatomic medullary locking (AML) implants. Rotational micromotion, permanent rotational displacement, and slop displacement between bone and implant were measured with linearly variable differential transducers under torsional loading. The line-to-line reamed group showed significantly greater motion than both underreamed groups for all micromotion parameters. This was especially true for the slop displacement test, which revealed large amounts of displacement after a single moderate torsional load, whereas in the underreamed groups significantly less loosening was found. The line-to-line reaming technique did not achieve good rotational fixation of the femoral component. Superior rotational stability was accomplished only when the diaphysis was underreamed and tight diaphyseal fixation was achieved. The extent of the porous coating on the stem did not have a significant effect. PMID- 1735212 TI - The blood supply of the human distal radioulnar joint and the microvasculature of its articular disk. AB - The arterial blood supply of the distal radioulnar joint was investigated in 35 upper extremities taken from 22 fresh cadavers (11 newborns and 11 adults using the India ink injection and tissue-clearing techniques according to Spalteholz). Microvasculature of the articular disk of the distal radioulnar joint was also performed in 35 articular disks taken from 22 fresh human cadavers, 11 newborn and 11 adults using the same technique. It was found that the general blood supply to the joint is received mainly from the palmar and dorsal branches of the anterior interosseous artery. These branches, after dividing at the proximal border of the pronator quadratus, arborize in a fanlike fashion around the joint and their small ramifications penetrate and vascularize the capsule and the articular disk from the palmar, dorsal, and medial sides. The terminal branches of the anterior interosseous artery reinforced by the posterior interosseous artery and a small branch of the ulnar artery give the direct peridiscal vessels to the palmar, medial, and dorsal margins of the articular disk, which arborize and anastomose with one another and form the terminal capillary networks that end at the peripheral segments of the disk in a series of terminal capillary loops, leaving the inner segments devoid of blood vessels. The posterior interosseous artery anastomoses at the distal part of the forearm with one of the terminal rami of the dorsal branch of the anterior interosseous artery and, in that way, contribute to the vascularization of the dorsal capsule of the distal radioulnar joint. The ulnar artery gives off a small branch that anastomoses with one of the terminal ramifications of the palmar branch of the anterior interosseous artery and contributes to the formation of a small arterial arch on the anteromedial side of the distal ulna, supplying the anteromedial capsule and the basistyloid area of the ulna. Both ulnar and radial arteries contribute to the vascularity of the joint through the collateral network of the palmar and dorsal carpal arches. In the articular disk, the major central portion of the disk is avascular and only its peripheral, palmar, medial, and dorsal margins are vascularized. The proportion of vascularized zone to avascular zone depends on the age of the subject and, in newborns, is approximately 33%. In adults, only 25% of the peripheral segments are vascularized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735213 TI - Titanium hip implants for improved magnetic resonance and computed tomography examinations. AB - The value of magnetic resonance imaging (MRI) for assessment of the hip has been demonstrated, particularly in cases of avascular necrosis. Magnetic resonance imaging can be used to provide anatomic evaluation of the femoral head, acetabulum, hip joint, joint fluid, and the surrounding structures. MR examinations of two patients with hip fractures fixed with stainless steel hip implants were compared with nine patients with hip fractures fixed with titanium hip implants, one of which showed avascular necrosis of the femoral head. The titanium implants resulted in less MRI artifacts, allowing for improved depiction of the femoral head and surrounding soft tissue. For this reason titanium fixation devices are recommended as a substitute for stainless steel in the hip joint region in a patient who may need future MR examination. PMID- 1735214 TI - Transient osteopenia of the hip joint in children. AB - Two pediatric cases of transient osteopenia of the hip joint are reported. Roentgenograms showed bone atrophy in the femoral head, the femoral neck, and the pelvis. Bone scintigrams showed a higher accumulation. At the follow-up study, osteopenia disappeared in both cases, however coxa magna was recognized in one case. The emphasis is on differential diagnosis from more severe disease, because the syndrome is characterized by spontaneous resolution. PMID- 1735215 TI - Preoperative flexion. Does it influence postoperative flexion after posterior cruciate-retaining total knee arthroplasty? AB - This study analyzed data from 313 posterior-cruciate-sparing total knee replacements to determine the influence of preoperative flexion on postoperative flexion. The patients with limited flexion preoperatively demonstrated an improvement in flexion postoperatively. By contrast, patients with more than 105 degrees of flexion preoperatively demonstrated a decrease in flexion postoperatively. The study indicated a migration towards the mean range of motion. These findings were true for the total pool of patients and for each subgroup of patients based on diagnosis, cement status of the tibia, and implant type. The data suggests that flexion does not change beyond the first postoperative year. PMID- 1735216 TI - The effect of patellar button placement and femoral component design on patellar tracking in total knee arthroplasty. AB - The effects of patellar button position and femoral component design on patellar tracking were investigated roentgenographically and arthroscopically using fresh frozen adult anatomic specimen knees. Patellar tracking was evaluated for medial/lateral position and tilting angle deviation by comparing preoperative normal values to total knee replacement performance with the following variables: (1) femoral component design; symmetrical total condylar type with a 3-mm central patellar groove and a component with a 3-mm raised lateral patellar flange and 1 mm deepened patellar groove; and (2) patellar button placement; central insertion; and 10-mm medialized insertion. In the roentgenographic study, medialized position of the patellar button allowed the bony portion of the patella to assume its normal lateral position and tilt throughout the knee range of motion. A combination of medialized position of the patellar button and deepening of the patellar groove provided the most anatomically correct position and the most normal tilting of the bony structure of the patella. In the arthroscopic study, the centralized patellar position caused significant lateral tracking and subluxation relative to the femoral component, whereas the medialized position eliminated this tracking disorder. Deepening the patellar groove minimized the intraarticular tracking abnormality and constrained the patellar button in the patellar groove. These results show that the position of the patellar button and femoral component design exert a major influence on patellar tracking. PMID- 1735217 TI - Relation of the fibular head sign to other signs of anterior cruciate ligament insufficiency. A follow-up letter to the editor. AB - The fibular head sign is a clinical finding that seems not to have been previously reported for the diagnosis of chronic anterior cruciate ligament insufficiency (ACLI) associated with lateral rotatory instability of the knee joint. The fibular head could be palpated as a prominent bony lump, felt subcutaneously in the posterior lateral corner of the popliteal fossa. In a prospective study of 20 patients with ACLI, the mean age of the patients (15 males, five females) at the time of assessment was 26 years (range, 18-57 years). The left knee was involved in 11 patients, the right knee in the remaining nine patients. All the patients sustained their knee ligament injury in sporting activities except one patient who was involved in a motor vehicular accident. The majority of the patients had instability-related symptoms for more than six months. After history taking, physical examination in the clinic, and examination under anesthesia, and arthroscopy in the operating room of all patients, it was determined that there were 13 ACL injuries, four posterior cruciate ligament (PCL) injuries, and three combined A/PCL injuries. All ACL injury patients had a prominent fibular head sign. Other associated signs included passive hyperextension of 10-20 degrees, and major anterolateral, and to a lesser degree a posterolateral, rotatory instability. The fibular head sign was negative in isolated posterior cruciate injuries and in combined A/PCL injuries. PMID- 1735218 TI - Soft-tissue management with prosthetic replacement for sarcomas around the knee. AB - The soft-tissue management was reviewed in 46 consecutive primary and nine revision segmental knee resections with prosthetic reconstruction performed for sarcomas around the knee. From January 1983 until August 1986, before the extensive use of free-tissue transfer in these patients, 20 primary segmental knee reconstructions were performed with five patients receiving gastrocnemius rotation flaps, and one patient receiving a late free flap (Group I). In this group, three patients were converted to an above-knee amputation because of wound problems. From August 1986 to August 1988, free-tissue transfer was available and extensively used in addition to rotation flaps to manage 26 primary (Group II) and nine revision (Group III) segmental knee reconstructions. In contrast to Group I, none of the patients in Groups II or III required amputation or conversion to a nonlimb-sparing procedure for soft-tissue management. None of the patients in this study received radiation therapy to their extremities. Chemotherapy protocols were similar in Groups I and II with 22 of 26 patients in Group I and 19 of 20 in Group II receiving treatment. The availability and expertise to perform free and rotational flaps at the time of initial excision provides greater selection and improved outcome for those patients whose wounds are closed primarily. The capability to perform free and rotation flaps at initial resection and for postoperative wound management is a major determinant of ultimate success in patients having reconstruction after excision of sarcomas about the knee. PMID- 1735219 TI - The innervation of the human meniscus. AB - Fourteen menisci from seven anatomic specimens were examined to identify their innervation. After staining by a modified gold chloride method, the menisci were sectioned on a sliding microtome and were studied under a light microscope. Free nerve endings in the peripheral and the medial thirds of the meniscal body were identified, and three types of encapsulated mechanoreceptors were found in the anterior and posterior horns. Based on these findings and a review of the relevant literature, it is considered that menisci both receive and transmit proprioceptive information. Therefore, they not only are stabilizers of this joint, but also contribute to the function of deep sensitivity. PMID- 1735220 TI - C-reactive protein (CRP) levels after elective orthopedic surgery. AB - The levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined by serial measurements after four types of uncomplicated elective orthopedic surgery. The type of operations chosen for this study were total hip arthroplasty (primary, n = 109; and revisions caused by aseptic loosening, n = 9), unicondylar knee arthroplasty (n = 39), and lumbar microdiskectomy (n = 36). In all patients, CRP levels increased after surgery, reaching peak levels on the third day after hip arthroplasties (primary, 116 +/- 43 mg/l; revisions, 136 +/- 58 mg/l) and on the second day after knee arthroplasties (140 +/- 46 mg/l) and lumbar microdiskectomy (48 +/- 27 mg/l). C-reactive protein levels usually dropped to normal (less than 10 mg/l) within 21 days after surgery. No correlations were found between CRP response and the type of anesthesia, amount of bleeding, transfusion, operation time, administered drugs, age, or gender. Erythrocyte sedimentation rate increased to peak levels about five days after surgery, followed by a slow and irregular decrease. Still, 42 days after uncomplicated operations ESR often remained elevated. In conclusion, the level of CRP must be considered a better diagnostic aid for the early detection of postoperative infections than ESR. It can be assumed that the rapid decline in CRP after uncomplicated orthopedic surgery will be interrupted by a second rise or by a persisting elevated level if infectious complications occur. PMID- 1735221 TI - Arthroscopic management of pyarthrosis. AB - Sixteen patients (average age, 38 years; range, 20-63 years) with pyarthrosis were treated during a ten-year period by arthroscopic techniques consisting of joint debridement and application of suction drains, combined with appropriate antibiotics. There were 13 knees, two shoulders, and one ankle in the series. At the first visit to the authors' institution, patients typically had fever, leukocytosis, elevated sedimentation rate, and localized joint findings, such as generalized tenderness, swelling, effusion, and painful, limited range of motion in almost every joint involved. Most patients were seen two to five days after the onset of symptoms. After the initial culture and sensitivity were obtained and broad-spectrum antibiotics were administered, all patients were taken to the operating room on an emergency basis. At an average follow-up evaluation of 36 months (range, 14-48 months), the results have been excellent to good, without evidence of recurrence. PMID- 1735222 TI - A model for evaluating the strength of bones lengthened by distraction osteogenesis. AB - In an effort to evaluate the strength of bones lengthened by distraction osteogenesis, a modified Ilizarov-type external fixator was applied to the right tibiae of five adult mongrel dogs. Diaphyseal corticotomies were performed, and distraction (lengthening) was carried out at a rate of approximately 1 mm per day for 20 days. After completion of the lengthening, the animals were killed, the fixators were removed, and the right and left tibiae were harvested and stripped of soft tissue. The ends of all harvested bones were fixated in polymethylmethacrylate to allow testing on a materials testing system (MTS) machine. Testing under torsional loads was performed on the MTS machine (50 degrees maximum angle of rotation at ten seconds) until failure. The right tibiae were lengthened an average of 12 mm (range, 7-15 mm). The slopes of the linear portion of the torque versus rotation curves were determined. A comparison of slopes revealed a mean change in stiffness between test and control bones of 20.32% (range, 0.64%-40.5%). All tibiae exhibiting mature regenerate bone demonstrated stiffness greater than the matched controls (range, 0.64-24.09% stiffer). Four of five dogs had problems with proximal and distal ring impingement. This study presents a reproducible model for evaluating the strength of bones lengthened by distraction osteogenesis. The lengthened bones that exhibited bony or mature regeneration were as strong as the control bones. PMID- 1735223 TI - Spontaneous gluteal artery rupture resulting in compartment syndrome and sciatic neuropathy. Report of a case in Ehlers-Danlos syndrome. AB - Spontaneous arterial rupture is an uncommon but potentially life-threatening event. In this case spontaneous bleeding from a gluteal artery resulted in a gluteal compartment syndrome and sciatic neuropathy. Bleeding is best managed by arteriography and embolization. Similar in pathophysiology to the more common leg and forearm compartment syndromes, gluteal compartment syndromes are treated with fasciotomy. Spontaneous arterial bleeding in an extremity may be the initial symptom in patients with a rare form of Ehlers-Danlos syndrome. Additional evaluation for the presence of significant abdominal and intracranial arterial involvement is mandatory. Family members should also be evaluated for this hereditary condition. PMID- 1735224 TI - Rib perichondrial autografts in full-thickness articular cartilage defects in rabbits. AB - This study investigated the resurfacing of full-thickness articular defects in the adult rabbit medial femoral condyle using a rib perichondrial graft. The graft was secured to a 4-mm-diameter bone core removed from the femoral condyle. Two postoperative treatment protocols were studied: one group had ad libitum cage activity (CAGE; n = 95) and the other group received two weeks of passive motion (PM; n = 73; eight hours per day, five days per week) followed by cage activity. Animals in both groups were killed at six, 12, 26, and 52 weeks. Repair tissue resembling hyaline cartilage formed in a majority of animals at all time periods and in both postoperative treatment groups. The overall success rates in which repair tissue formed were 58% in the CAGE group and 56% in the PM group. However, over time, a maturation of the neocartilage into nearly normal hyaline articular cartilage was noted with the percentage of Type II collagen increasing from 55% at six weeks to 82% at one year. The complex shear modulus of the repair tissue for both groups became similar to normal cartilage with increased healing time. There was no statistical difference in shear moduli between the two treatment modalities. These results show that cartilage repair tissue derived from rib perichondrium could mature into hyaline articular cartilage over time and would not degrade by one year after repair. PMID- 1735225 TI - Longitudinal growth and growth-plate activity in the lower extremity. AB - Teleroentgenograms of the lower extremity in 244 children (123 boys and 121 girls) were made at six-month intervals from age seven until skeletal maturity. Lengths were measured to determine the growth remaining in the femur and tibia. The subjects were healthy, well-nourished, middle class Americans, mostly of Northwest European descent. The percentage of growth occurring at each lower extremity growth plate was determined by roentgenstereophotogrametric analysis. The growth occurring at the distal femoral and proximal tibial growth plates was determined by multiplying the proportion of growth occurring at each age by the longitudinal growth remaining. The proportion of growth occurring at each growth plate is not equal. Also, growth-plate activity is not constant or average throughout growth. Overall, approximately 70% of growth in the femur occurs at the distal growth plate. The proportion of growth occurring in the distal femoral growth plate in girls varies from 60% at seven years of age to 90% at age 14. Similarly, the contribution of the distal femoral growth plate in boys varies from 55% at seven years of age to 90% at age 16. Overall, the contribution of the proximal tibial growth plate is approximately 57%. In girls, this varies from 50% at seven years of age to 80% at age 14. In boys it varies from 50% at seven years of age to 80% at age 16. From the age of seven to skeletal maturity, the distal femur contributes approximately 1.3 cm per year to femoral growth, except in the last two years, when it contributes half that amount.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735226 TI - Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis. AB - In the adult rat femur, lifting a periosteum strip with microscopic bone flakes on its deep surface, if performed without damaging the surrounding microcirculation, rapidly leads to new bone formation and angiogenesis. Using vascular labeling, the pericytes and endothelial cells (ECs) were labeled with monastral blue (MB) in the preformed, preexisting postcapillary venules of the periosteal microcirculation. MB was detectable by light and electron microscopy and it persisted in some of the daughter cells. Between one and 21 hours, the MB labeling was restricted to the pericytes and ECs of postcapillary venules. Immediately afterward, both pericytes and ECs of these vessels were activated and continued to show MB. The phenomenon of pericyte activation includes enlargement, disruption of their basal lamina, separation from the walls of the preformed vessels, and the presence of mitotic figures. At this stage, activated pericytes with MB in their cytoplasm, fibroblast-like cells, and transitional cell forms between them were seen in interstitial areas. After 27 hours, vascular buds appeared and MB was detected in some ECs and pericytes. Between three and six days, when bone-tissue development was observed, some osteoblasts were MB labeled. Previous findings support the hypothesis that when the periosteum is activated, the process of bone formation from cells already present in the periosteum is augmented by proliferation and differentiation of pericytes, which contribute a supplementary population of osteoprogenitor cells. PMID- 1735227 TI - The pericyte as a possible osteoblast progenitor cell. AB - Bovine capillary and microvessel pericytes were grown in monolayer in standard tissue culture medium supplemented with 10% newborn calf serum at various oxygen tensions for up to ten weeks. The pericytes synthesized alkaline phosphatase and formed colonies that mineralized. Energy dispersive X-ray spectrometry revealed the presence of calcium and phosphate, showed positive staining for collagen and glycosaminoglycan, and, most importantly, demonstrated the synthesis of osteocalcin. Cell proliferation, hydroxyproline production, and alkaline phosphatase synthesis were greatest in 3% oxygen, whereas osteocalcin production was least in 3% oxygen. These findings demonstrate that the capillary or microvessel pericyte exhibits phenotypic expressions in vitro that are similar to that of in vitro bone cells, and these expressions may be somewhat oxygen dependent. It is suggested from these findings that the capillary or microvessel pericyte may be an osteoblast precursor cell. PMID- 1735228 TI - Histologic structure of the articular disk of the human distal radioulnar joint. AB - A histologic study of the structure of the articular disk of the distal radioulnar joint in humans was performed on 57 disks from 37 fresh cadavers that included fetuses and individuals up to age 65 years. The specimens were stained with hematoxylin and eosin, orcein, and Mallory and Mann-Dominici's methods, and studied with the light microscopy. It was found that the disks of adults were basically formed of the so-called fibrocartilagenous tissue composed of an intercellular substance in which there were interwoven wavelike collagen fiber bundles and between them three specific types of cells: (1) rather sparse fibrocytes mostly situated in dorsal and palmar margins, (2) predominant and constant chondroid cells dispersed throughout the disk, and (3) less-frequent real chondocytes distributed mostly in the central parts. This basic tissue is modified according to the age of the subjects and functional requirements. In fetuses and newborns, it is almost completely fibrous and very cellular, while in adults, it is more cartilaginous with significantly reduced cellularity. The structure of various parts of disks is adapted to the functional stresses exerted on them. In central parts exposed to pressure, the tissue is more cartilaginous, while peripheral, massive margins, subjected mostly to traction, are built in a ligamentlike pattern. The ulnar and carpal surfaces are adapted to the gliding movements of the ulna and carpus. It is concluded that the articular disk in humans, which is basically of fibrocartilagineous nature, is a dynamic structure biomechanically, predetermined and changing with aging. PMID- 1735229 TI - Partial excision of lower shaft of ulna for deformity following Colles's fracture. 1913. PMID- 1735230 TI - Serum and other calcium fractions in patients after severe musculoskeletal trauma. AB - Alterations in serum calcium fractions after trauma may be of clinical importance. For investigation of this problem, serum calcium fractions were studied prospectively in 42 patients with severe musculoskeletal injuries. The severity of trauma was assessed with the Apache II severity of disease classification system. Serum ionized calcium, total calcium, pH, albumin, and arterial blood gases were measured daily for the first five days after admission. The fat embolism syndrome developed in eight patients; they were more severely injured than the others, and they had significantly lower levels of serum ionized calcium for all five days of the study. There was a strong negative correlation between the Apache II score and serum ionized calcium. Ionized hypocalcemia has a strong association with development of the complications of severe musculoskeletal trauma, such as the fat embolism syndrome. PMID- 1735231 TI - The distal radioulnar joint. Anatomic and functional considerations. AB - The distal radioulnar joint is functionally coupled with the proximal radioulnar joint, thus forming a mechanism for the longitudinal rotation of the hand. Distal radioulnar mobility is derived from the geometry of the joint, joint surfaces, and radioulnar connections. There is a structural and functional separation between the distal radioulnar and carpal joints, giving the possibility of pronation and supination in every position of the hand to the forearm. As for the stability of the joints involved, the ulnar articular disk plays an essential role. Being part of both distal radioulnar and carpal joints, the disk has very specific morphologic features that not only are individualized to the function of both joints but also stabilize the joints in their independent movements. Developmental data give the strong impression of an architectural scheme, of which the distal radioulnar joint is only a part. Traumatic lesions at the distal radioulnar joint and disturbances in normal distal radioulnar alignment have to be viewed, therefore, in a wider context. PMID- 1735232 TI - Biomechanics of the distal radioulnar joint. AB - The distal radioulnar joint (DRUJ) is a complex joint involved in pronosupination and ulnocarpal motion and support. The ulnar head, in a rolling, sliding motion, moves from the dorsal to the volar rim of the sigmoid notch as the joint moves from pronation to supination. The triangular fibrocartilage (TFC) is taut first dorsally and then volarly in the same sequence. The ulnar carpus is supported variably, as a function of ulnar length relative to the radial articular surface, by the pole of the distal ulna through the TFC. The TFC does not resist the pistonlike movement of the DRUJ, which occurs under dynamic loading. The coronal alignment of the DRUJ minimizes shear stress on the articular surfaces because of its alignment with the rotational axis of the forearm. Ulnar variance is a factor in the development of several clinical conditions. PMID- 1735233 TI - Evolution of the distal radioulnar joint. AB - The evolution of the wrist joint began 400 million years ago with the pectoral fins in primitive fish. The five-rayed extremity with 13 carpal bones and a syndesmotic distal radioulnar joint first appeared in the primitive amphibian, Eryops, some 230 million years ago. These characteristics remained similar through the evolution of the amphibians and of mammals and were retained when primates evolved to hominids. As later-developing, larger-sized hominids began competing for food, brachiation (the ability to swing from tree branch to tree branch) became more important, and a synovial distal radioulnar joint evolved, allowing pronation/supination of the wrist. The development of bipedalism freed the upper extremity from the requirements of locomotion, placing greater emphasis on increasing wrist mobility. The ability to supinate and pronate was an immense advantage to hominids in caring for their young, defending themselves, and gathering food. It was also critical in efficient tool handling, which developed two million years ago. The mobility of the distal radioulnar joint, along with the prehensile thumb and increasing brain function, are hallmarks of the late evolving hominids. PMID- 1735234 TI - The distal radioulnar joint in relation to the whole forearm. AB - The functional anatomy of the distal radioulnar joint was studied in relation to the whole forearm, using three fresh-frozen, above-elbow amputation specimens. The specimens demonstrate how the proximal and distal radioulnar joints together form a bicondylar joint of special character. The proximal "condyle," the radial head, rotates axially, whereas the distal "condyle," the ulnar head, is fixed with respect to rotation. The ordinary articulation of a bicondylar joint (pure axial rotation) is thereby changed into pronation-supination. Axial rotation is preserved proximally, while distally the radius swings around the ulnar head. The mobile radius is distally attached to the stable ulnar head by the dorsal and volar radioulnar ligaments, the dorsal ligament being tight for stabilization in supination and the volar ligament being tight in pronation. The ulnar head also serves as a keystone, carrying the load of the radius. Removal of the ulnar head allows the radius to "fall in" towards the ulna, with narrowing of the interosseous space. PMID- 1735235 TI - Traumatic disruption of the triangular fibrocartilage complex. Pathoanatomy. AB - The surgical pathology in 42 cases of traumatic triangular fibrocartilage complex (TFCC) disruption comprised a spectrum of injury resulting in five basic stages of increasingly severe ulnar wrist instability. In all cases, detachment of the articular disk from its ulnar insertion was the principal cause of distal radioulnar joint instability; in 28 (67%), concomitant injury to the adjacent extensor carpi ulnaris sheath, the ulnocarpal ligaments, or the peritriquetral ligaments compounded the instability. Thus, rather than an isolated event, peripheral disruption of the disk often proved the major constituent of multicomponent lesions--lesions consistently suitable for repair. In this series of destabilizing TFCC disruption requiring operative treatment, awareness that some injuries selectively affect the articular disk, whereas others compromise wider zones of wrist anatomy, was essential to successful surgery. PMID- 1735236 TI - The distal joint of the radius and ulna. Diagnostic studies and treatment rationale. AB - Three areas of functional anatomy are present in the distal ulna. Each of these has a specific function in load bearing of the wrist, rotation of the forearm, and maintenance of the relationship between the radius and ulna. The distal portion of the ulna serves as a suspensory post for ligaments that stabilize the ulnar border of the wrist. The midportion of the distal ulna contains the load bearing triangular fibrocartilage complex. The proximal portion of the distal ulna articulates with the radius at the sigmoid notch and participates in forearm rotation. Each of these areas is assessed in problems related to ligament instability, load bearing, and range of motion. Mechanical problems that affect the distal joint of the radius and ulna include the affects of trauma, degenerative change, and inflammatory disease. Each of these requires evaluation in the treatment of joint derangement. Diagnostic studies that relate to problems in the distal radioulnar joint area include standard roentgenographs, arthrograms, magnetic resonance (MR) scanning, and arthroscopy. Each of these studies has particular advantages and disadvantages in providing data for analysis of joint malfunction. A medical history, physical examination, and use of proper diagnostic studies will assist in an appropriate diagnosis of problems in the distal joint of the radius and ulna. PMID- 1735237 TI - Radial head fractures and their effect on the distal radioulnar joint. A rationale for treatment. AB - Nineteen patients were treated with open reduction and internal fixation for radial head fractures. Open reduction and internal fixation was performed to avoid radial head excision and the possible development of distal radioulnar joint dysfunction. Follow-up observation, which averaged 11.7 months, revealed that no patient developed wrist pain. Range of motion of the elbow and forearm was found to be complete in 14 patients and minimally restricted in four. Fourteen patients were pain free with full activity, and four had mild to moderate pain after heavy labor. One patient subsequently required radial head excision. Based on these findings and the authors continued disappointment with treatment of distal radioulnar joint dysfunction caused by proximal radial migration after radial head excision, the authors recommend early open reduction and internal fixation of all displaced or angulated radial head fractures. PMID- 1735238 TI - A Darrach procedure for distal ulnar pathology derangements. AB - Despite technologic advancements including arthrography, arthroscopy, and magnetic resonance imaging, pain in the distal radioulnar and ulnar carpal joints continues to baffle clinicians. Before the wide use of these diagnostic tests, the authors based their diagnosis of distal ulnar carpal joint derangement on the physical examination, history, and plain film roentgenographs. For eight patients who did not respond to conservative measures, a limited Darrach procedure was performed with highly satisfactory results. The specific technical aspects of this procedure are described. The postoperative results of the patients are presented with one to eight years of follow-up evaluation. PMID- 1735240 TI - Abstracts of papers presented at the Ninety-Third Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. Orlando, Florida, March 18 20, 1992. PMID- 1735239 TI - Complex dislocations of the distal radioulnar joint. Recognition and management. AB - Contrary to most reported series, it has been the authors' experience that dislocations of the distal radioulnar joint (DRUJ) associated with fractures of the forearm are frequently irreducible. This report reviews the authors' experience with these injuries, focusing on the recognition and management of what the authors call "complex" DRUJ dislocations: dislocations characterized by obvious irreducibility, recurrent subluxation, or "mushy" reduction caused by soft tissue or bone interposition. From 1984 until 1989, at the authors' institution, 11 patients were treated for fractures of the radius associated with dislocations of the DRUJ. Eight of these patients had a classic Galeazzi fracture dislocation. Two patients had severe open radius and ulnar fractures. One had an unstable comminuted intraarticular fracture of the distal radius. Of these 11 patients, four had "complex" dislocations of the DRUJ. In two cases, the extensor carpi ulnaris was displaced volar to the distal ulna, necessitating open reduction. A third case involved delayed recognition of multiple wrist and forearm joint dislocations associated with a severe open fracture of both bones of the forearm and required late exploration, reduction, and temporary internal fixation. A fourth case involved recurrent dorsal subluxation of the distal ulna after open reduction and internal fixation of a comminuted intraarticular distal radius fracture. It is clear that complex dislocations of the DRUJ occur more frequently than previously noted. Careful attention to these injuries during initial reduction attempts will reveal "mushy" or unobtainable reductions, an important indication for exploration for entrapped tendon, bone, or soft tissue. PMID- 1735241 TI - Cardiac tumors: diagnosis and management. AB - The first step towards the diagnosis of cardiac neoplasia is made when the clinician considers the diagnosis. While the classically described signs and symptoms of left-atrial myxomas are noteworthy, the vast majority of patients present with symptomatology that is less specific--either of a constitutional nature, or related to right- or left-sided congestion. Likewise, the physical examination may rarely disclose classic auscultatory signs, but is more likely to confirm the presence of the right- or left-sided congestion inferred from history. Peripheral, embolic, or vasculitis lesions should raise suspicion of the diagnosis. Nevertheless, the majority of patients will be diagnosed by the unexpected detection of a tumor at the time of echocardiography. Transthoracic echocardiography remains the procedure of choice in screening for cardiac neoplasia. It has excellent sensitivity for intracavitary and endocardial lesions. Myocardial lesions are also well imaged. Pericardial lesions, with or without extension into contiguous structures, are poorly visualized and, here, magnetic resonance imaging is unquestionably the superior investigative approach. Further, a limited degree of tissue characterization is possible with the latter technology. Transesophageal echocardiography is ideally suited for the examination of suspected tumors involving the atria, interatrial septum, superior vena cava, atrioventricular valves and, to a lesser extent, the ventricles. These three imaging modalities clearly complement one another and the choice of application will depend upon factors including the patient's transthoracic echogenicity, the availability of magnetic resonance imaging or transesophageal echocardiography, cost, and the physical status of the patient. PMID- 1735242 TI - Investigative bronchoscopy in subjects with asthma and other obstructive pulmonary diseases. Whether and when. PMID- 1735243 TI - Preoperative physiology and lung resection. Scan? Exercise? Both? PMID- 1735244 TI - Is a VO2 plateau necessary? PMID- 1735245 TI - Still going around on the flow-volume loop. PMID- 1735246 TI - Aortic dissection. The diagnostic dilemma resolved. PMID- 1735247 TI - Disposable jet nebulizers. How reliable are they? AB - We studied the frequency of malfunction, variability in rate of nebulization, and effect of this variability on aerosol particle size of eight disposable jet nebulizer models produced by six manufacturers. Four of eight models showed visual signs of malfunction, including spraying of large, individually visible droplets, leaking of nebulizer solution, and air leaks that completely prevented nebulization. Variability of nebulization rate within specific models ranged from 57 to 129 percent. The model with the largest variability of nebulization rate was also associated with an unacceptably large variability in particle size. In contrast, two models with smaller variability in nebulization rate had greater consistency of particle size. These results indicate poor quality control by some manufacturers in the disposable nebulizer industry. The data suggest that purchasing agents should consider reliability as well as cost before selecting a specific nebulizer model and that their evaluation should include physical testing of multiple units of each model under consideration. PMID- 1735248 TI - Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group. AB - STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF. PMID- 1735249 TI - Postoperative pleural changes after coronary revascularization. Comparison between saphenous vein and internal mammary artery grafting. AB - Coronary artery bypass grafting (CABG) is commonly performed with a saphenous vein graft (SVG) and/or an internal mammary artery graft (IMA). We hypothesized that there would be a higher incidence of pleural changes after CABG in patients who underwent IMA grafting because pleurotomy is usually performed. In the present study, the pre and the 6th postoperative day chest roentgenograms of 122 patients who received CABG were reviewed. The incidence of effusion in the patients who received only SVG was 43 percent (23/54) and did not differ significantly (p greater than 0.05) from the incidence in the patients who also had IMA 41 percent (28/68). Almost all of the patients (43/51) had unilateral left-sided pleural effusions. Most of the effusions were small and did not require treatment. The incidence of effusion was not higher in patients with enlargement of their cardiac silhouette or atelectasis and was not related to the presence of chest tubes. The incidence of pleural thickening was higher in the IMA group (49 percent) than in the SVG group (31 percent) but the difference did not achieve statistical significance (p greater than 0.05). We conclude that there is a high (approximately 40 percent) incidence of small effusions and thickening after CABG. The incidence of pleural effusion and pleural thickening do not appear to be influenced by the type of surgery (IMA vs SVG). We speculate that the effusions are due to pericardial inflammation. PMID- 1735250 TI - Determinants of outcome in lesions of the thoracic aorta in patients with multiorgan system trauma. AB - Of all patients presenting at our level 1 trauma center with multiorgan system injuries, 33 have been identified with acute lesions of the thoracic aorta. Mean severity injury score was 24 +/- 3. Four patients underwent resuscitative thoracotomy upon arrival in the emergency department. One survived and fully recovered. The rest underwent diagnostic procedures and repair of aortic lesions in conjunction with surgical treatment of other injured organ systems. The overall survival rate was 82 percent. Survivors arrived significantly faster to the ED and had lesser degree of multiorgan system injuries. There was no difference in the time spent to make the diagnosis of acute aortic disruption for survivors and nonsurvivors, nor was a difference in time to arrive in the operating room once the diagnosis of aortic injury has been established. Morbidity was related to ischemia to distal organs in four patients of whom two presented with multiple lesions of the thoracic aorta; two remained paralyzed and two had only lower limb spasticity. All discharged survivors were alive at 12 months' follow-up. The type of surgical repair did not influence the outcome of patients with single, typical aortic lesions; however, "clamp/sew" technique was not adequate when multiple aortic tears were found intraoperatively. The outcome of surgical treatment of the traumatic aortic lesions of patients with polytrauma may be influenced by the speed of arrival to the ED, the magnitude of multiorgan system involvement, and the application of appropriate surgical technique for repair according to the intrathoracic findings and the timing of aortic repair vis-a-vis other surgical treatment. PMID- 1735251 TI - Respiratory response and ventilatory muscle recruitment during arm elevation in normal subjects. AB - Despite the fact that the arms are used extensively in daily life and that some of the muscles of the shoulder girdle share both a respiratory and a positional function for the arms, surprisingly little is known about the respiratory response to unsupported upper extremity activity. To determine the respiratory consequences of simple arm elevation during tidal breathing, we measured minute ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR), oxygen uptake (VO2), and carbon dioxide production (VCO2) in 22 normal subjects seated with arms elevated in front of them to shoulder level (AE) for 2 min and down at the sides (AD) for the same time period. The sequence was randomized. Compared with AD, during AE there were significant increases in VO2 (336 +/- 18 vs 289 +/- 14 ml/min, p less than 0.001), VCO2 (315 +/- 23 vs 245 +/- 16 ml/min, p less than 0.001), HR (84 +/- 6 vs 73 +/- 4 beats/min, p less than 0.05), VE (11.5 +/- 0.9 vs 9.3 +/- 0.6 L/min, p less than 0.001), and VT (868 +/- 66 vs 721 +/- 48 ml, p less than 0.001). In 11 subjects, breath-by-breath metabolic and ventilatory parameters were studied with AD for 2 min, AE for 2 min, and with AD for 3 min while also recording gastric (Pg), pleural (Ppl), and transdiaphragmatic pressures (Pdi). With AE, there was a significant increase in Pg at end inspiration (PgI, 15.4 +/- 3.2 vs 11.9 +/- 2.7 cm H2O, p less than 0.01) and in Pdi (26.5 +/- 3.4 vs 21.4 +/- 2.4 cm H2O, p less than 0.01) with no change in Pg at end expiration (PgE) or in Ppl. The increases in VO2, VCO2, VE, and VT during arm elevation persisted for 2 min after arm lowering, whereas Pgi and Pdi abruptly dropped as the arms were lowered. We conclude that simple arm elevation during tidal breathing results in significant increases in metabolic and ventilatory requirements. These increased demands are associated with higher PgI and Pdi suggesting an increased diaphragmatic contribution to the generation of ventilatory pressures. The sudden drop in Pg with arm lowering indicate a change in ventilatory muscle and or torso recruitment independent of the metabolic drive and ventilatory needs. These findings may help explain the limitation that has been reported in some normal subjects and in many patients with lung disease during unsupported upper extremity activity. PMID- 1735252 TI - Sleep-disordered breathing in the healthy elderly. Clinically significant? AB - We evaluated sleep/wake, medical, and psychological parameters in a cohort of healthy men and women between 50 and 80 years of age. Consistent with previous investigations of sleep-disordered breathing (SDB) in older persons, nocturnal breathing disturbances were quite common in our normal-aged subjects, with more than 15 percent experiencing five or more SDB events per hour of sleep. However, when SDB indices were correlated with comprehensive measures of daytime functioning, the number of statistically significant relationships was at or below expectations from chance alone. Additionally, comparison of high-SDB subjects (AHI greater than or equal to 5) with low-SDB subjects (AHI less than 5) failed to reveal reliable differences on measures of daytime functioning. We conclude that SDB occurring in otherwise healthy older persons is not a cause for immediate concern, although longitudinal studies may yet demonstrate significant long-term sequelae of SDB in this population. PMID- 1735253 TI - Failure of inhaled corticosteroids to modify bronchoconstrictor or bronchodilator responsiveness in middle-aged smokers with mild airflow obstruction. AB - We have compared the effects of three-month periods of treatment with an inhaled corticosteroid, budesonide 600 micrograms twice daily and with placebo on bronchial responses to inhaled histamine and to bronchodilators in a double-blind crossover trial in 14 middle-aged male smokers (mean age, 59.6 years) with mild airways obstruction (mean FEV1 2.42 L, 80 percent predicted [range, 48 to 110 percent]). Responsiveness to inhaled histamine was assessed monthly by the provocative concentration (mg/ml) reducing FEV1 by 20 percent (PC20). Bronchodilator response to a combination of inhaled salbutamol (5 mg) and ipratropium (0.5 mg) was assessed before and after three months' treatment. Compliance with treatment was checked by weighing aerosol canisters, and by measuring plasma budesonide and metabolites. There was no significant change in FEV1 (budesonide mean 2.38 L [SEM 0.17] vs placebo 2.40 L [0.17]), vital capacity (budesonide mean 3.69 L [0.17] vs placebo 3.81 L [0.17]) or in bronchodilator responsiveness (mean increase over baseline FEV1, budesonide 11.6 [2.7] percent vs placebo 10.5 [3.2] percent). There was a small overall reduction in bronchoconstrictor responsiveness over the period of the trial, but there was no effect of 12 weeks of budesonide treatment compared with 12 weeks of placebo treatment (mean log PC20 during budesonide 0.595 [SEM 0.063], placebo 0.591 [SEM 0.055]). Following the three-month crossover trial, six men continued for nine more months to receive budesonide in a single-blind trial and the results were compared with those in six men who took no active treatment for the subsequent nine months. No improvements in baseline spirometry, home peak flow measurements, bronchoconstrictor or bronchodilator responsiveness were observed after 12 months of budesonide treatment. Thus, a regimen of budesonide treatment that consistently attenuates bronchial responsiveness in asthmatic subjects had no effect in these men; larger and longer trials will be required to establish whether a subgroup of smokers shows a favorable response. PMID- 1735254 TI - Exercise testing in the evaluation of patients at high risk for complications from lung resection. AB - Exercise testing was performed on 37 patients with resectable lung lesions who were deemed inoperable because of any of the following risk factors: (1) FEV1 less than or equal to 40 percent of predicted; (2) radionuclide calculated postlobectomy FEV1 less than or equal to 33 percent of predicted; or (3) arterial PCO2 greater than or equal to 45 mm Hg. The patients who reached a peak level of oxygen consumption during exercise (VO2Peak) of greater than or equal to 15 ml/kg/min were offered surgical treatment. Patients with a VO2Peak of less than 15 ml/kg/min were referred for nonsurgical management and excluded from the study. Eight patients underwent lung resection. Their pulmonary function revealed a severe obstructive lung defect with a group mean predicted FEV1 of 40 +/- 6 percent, an FEV1/FVC ratio of 47 +/- 10, a radionuclide calculated postlobectomy FEV1 of 31 +/- 4 percent, and a mean arterial PCO2 of 44 +/- 6 mm Hg. No relationship was found between each patient's exercise performance and spirometric function. Six of the patients had an uncomplicated postoperative course. Two patients had complications but no patient died as a result of surgery or postoperative complications. All patients were discharged from the hospital within 22 days (mean = 9.8 days). We conclude that exercise testing is a useful complement to conventional cardiopulmonary evaluation used in selecting patients for lung resection. PMID- 1735256 TI - Acute silicosis responding to corticosteroid therapy. AB - The course of acute silicosis usually is relentlessly progressive. Death results from cor pulmonale and respiratory failure, with mycobacterial infection a frequent serious complication. Attempts to treat the illness generally have been unavailing. We report an unusual case of acute silicosis in which improvement in clinical status, chest x-ray film findings and pulmonary function occurred following therapy with corticosteroids. To our knowledge, this is the first such case reported in the medical literature. PMID- 1735255 TI - Blood transfusion and lung function in children with thalassemia major. AB - Pulmonary function tests were performed at rest and following blood transfusion on 17 patients with thalassemia major. At rest, diffusion capacity was significantly reduced (mean of 57 percent), and forced vital capacity was mildly reduced (mean of 85 percent). In two of the patients, arterial oxygen tension was low. Other pulmonary function results were in the normal range. Following blood transfusion, a significant drop was seen in arterial oxygen tension (PaO2 of 22 mm Hg) and in forced vital capacity (FVC) of 32 percent. These changes were dramatic and require further explanation. PMID- 1735257 TI - Thoracic magnetic resonance imaging in the evaluation of HIV-1/AIDS pneumonitis. AB - Magnetic resonance imaging of the thorax was performed on ten occasions in eight HIV-positive patients with a clinical picture suggestive of Pneumocystis carinii pneumonia. The diagnosis of PCP was subsequently confirmed on six occasions. Patients without PCP had low MRI profusion scores, while four of six patients with PCP had MRI profusion scores greater than 6/21. Neither the chest roentgenogram appearance nor computer-generated T1 and T2 relaxation times could reliably distinguish between these two groups. Magnetic resonance imaging may be useful in the early and noninvasive diagnosis of PCP in HIV-positive patients. PMID- 1735258 TI - Pneumocystis carinii pneumonia in patients with connective tissue disease. AB - Four patients with PCP complicating a CTD are described. Rising serum lactate dehydrogenase levels were documented during an asymptomatic period associated with corticosteroid dosage tapering, weeks prior to the development of acute pulmonary symptoms. The diagnosis of PCP was established by FOB in each patient. PMID- 1735259 TI - Evening-to-morning blood pressure variations in snoring patients with and without obstructive sleep apnea. AB - This study was designed to test a hypothesis that patients with sleep apnea have higher blood pressure in the morning, following a night spent in apnea and hypoxemia, than in the evening. To accomplish this, we prospectively studied a set of 611 patients referred to our clinic because of suspicion of sleep apnea. All patients had full nocturnal polysomnography, including measurement of snoring. Blood pressure was measured in the evening, prior to onset of sleep, and in the morning, immediately on awakening. We found that patients without apnea and hypoxemia had lower blood pressure in the morning compared with the evening value, while patients with severe sleep apnea and hypoxemia had higher blood pressure in the morning; these evening-to-morning blood pressure differences, although statistically significant, were small, typically 1 to 4 mm Hg. Morning blood pressures were higher in patients with sleep apnea and hypoxemia than in nonapneic normoxic patients. However, this difference disappeared after the groups were matched for age and body mass index. We conclude that (1) patients with sleep apnea and nocturnal hypoxemia lose the expected morning dip in arterial blood pressure, and (2) age and body mass index are more important correlates of blood pressure than apnea and nocturnal oxygen desaturation. We speculate that the loss of evening-to-morning drop in blood pressure, if present over a long period of time, may lead to sustained elevations in arterial blood pressure frequently observed in patients with sleep apnea. PMID- 1735260 TI - Physiologic evaluation of pressure support ventilation by nasal mask in patients with stable COPD. AB - We evaluated the physiologic effects of pressure support ventilation by nasal route (NPSV) in eight patients with severe stable COPD and chronic hypercapnia who were randomly submitted to 2-h sessions of NPSV both with a portable ventilator (Respironics BIPAP device) and with a standard ventilator (Bird 6400ST device) at an inspiratory airway pressure of 22 cm H2O. Two sessions with each ventilator were performed using an FIO2 of 0.21 in each patient on two consecutive days. One patient did not tolerate either form of ventilation. Comparison of spontaneous with BIPAP ventilation showed a significant improvement in pH, PaCO2, and PaO2. Ventilatory pattern assessed by a respiratory inductive plethysmograph showed a significant increase in minute ventilation (VE), VT, and Ttot. Integrated surface diaphragmatic EMG activity measured only during BIPAP device ventilation decreased from that measured during spontaneous breathing. Similar changes in blood gases and ventilatory pattern were observed during ventilation by the Bird 6400ST except for VT/Ti ratio, which significantly increased. Comparison of baseline with measurements performed 12 h after the whole cycle of treatment showed a significant increase in pH and VE and a decrease in PaCO2. We conclude that short-term NPSV may be useful in improving respiratory pattern and blood gases in stable COPD patients with chronic hypercapnia. PMID- 1735261 TI - The effects of exercise on serum potassium levels. AB - In view of the significant influence of potassium on the heart, a decision was made to study the effect of exercise on this important ion in two exercise groups of different intensity. The first group consisted of 44 individuals with known coronary artery disease participating in a supervised cardiac rehabilitation program while the other consisted of 30 healthy joggers. Postexercise mean potassium levels were higher in both groups than resting baseline values. In addition, 5 of 44 participants in the coronary artery disease group experienced major potassium increases of 0.9 mmol/L or more while 7 of 30 healthy joggers experienced this magnitude of increase. Remaining unanswered is the question of whether such abrupt rises in potassium levels in this subset of patients alter their vulnerability to cardiac rhythm and conduction disturbances. A question is also raised as to whether rapid return of potassium levels to baseline postexercise contributes to any risks. PMID- 1735262 TI - Ventilation-perfusion inequalities during graft rejection in patients undergoing single lung transplantation for primary pulmonary hypertension. AB - We report herein data on single lung transplant (SLT) recipients with primary pulmonary hypertension (PPH). One patient did well following surgery but died on the 30th postoperative day due to cytomegalovirus pneumonia. The remaining two patients initially did well with unlimited exercise tolerance following transplantation, but then developed marked dyspnea on exertion and hypoxemia on postoperative days 144 and 120, respectively. Pulmonary function testing showed marked deterioration of function and transbronchial lung biopsy specimens revealed acute graft rejection in one patient and evidence of chronic graft rejection in the second patient. Quantitative ventilation-perfusion lung scanning demonstrated a marked decrease in ventilation to the transplanted lung in both cases associated with only a mild decrease in perfusion. This V/Q mismatch resulted in markedly decreased arterial oxygen saturations, widened alveolar arterial oxygen gradients, and clinically debilitating dyspnea. We conclude that rejection may result in significant V/Q mismatch and hypoxemia in PPH patients undergoing SLT, which may limit the use of this specific type of surgery for PPH. PMID- 1735263 TI - Impact of transesophageal echocardiography on the treatment of patients with aortic dissection. AB - To determine the impact of transesophageal echocardiography (TE) on the treatment of patients with aortic dissection, the clinical course and outcome of 18 patients with TE diagnosis of dissection were analyzed. Ascending aortic dissection was present in nine patients, of whom six had surgery with confirmation of TE findings. Angiography was performed in only two of these patients and was falsely negative in one patient. Angiography was not performed in the three patients who were not surgical candidates. In the nine patients who had descending aortic dissection, angiography was performed in seven patients, of whom two underwent surgery. Information provided by angiography did not change the treatment of these patients. Thus, TE provides a prompt and accurate diagnosis in aortic dissection obviating the need for angiography in most patients. PMID- 1735264 TI - The effects of verapamil on training in patients with ischemic heart disease. AB - Verapamil is a calcium-channel blocking agent with antianginal and antiarrhythmic properties that have been widely studied. Its myocardial depressant effect is well known. The purpose of this study was to examine the effects of verapamil on the training response in patients with ischemic heart disease. The study group consisted of 41 male patients with a mean age of 53.3 +/- 7.2 years who had suffered a myocardial infarction or had undergone coronary artery bypass surgery 8 to 12 weeks previously. They were chosen on a consecutive basis from eligible patients entering a cardiac rehabilitation program. With use of a double-blind technique, 21 patients were assigned to receive verapamil, 120 mg three times daily, while the other 20 were given an identical placebo. Each patient underwent exercise stress testing in the untreated state to permit comparison between tests performed on commencement and completion of training. The training effect was determined by comparing exercise response before and after the eight-week program. There was an increase in exercise duration (p less than 0.001) and a decrease in functional aerobic impairment (p less than 0.001), without difference between the two groups. Energy expenditure increased in both groups, but the highest level was achieved by those receiving active treatment (p less than 0.02). Heart rate for equal workload was significantly reduced after training (p less than 0.001), although this was lower in the placebo patients (p less than 0.001) and the patients who had a recent myocardial infarction (p less than 0.01). It appears that treatment with verapamil does not impair the development of a training effect in patients with ischemic heart disease who are undergoing organized training. PMID- 1735265 TI - ST segment depression in right-sided electrocardiographic leads in patients with acute myocardial infarction. AB - The presence of ST segment depression in right-sided electrocardiographic leads has been infrequently reported in the literature. We report the cases of two patients with anterolateral and posterior myocardial infarctions with ST segment depression in right-sided electrocardiographic leads. We hypothesize that this electrocardiographic change is a reciprocal expression of ST segment elevation of the opposing left ventricular wall. PMID- 1735266 TI - Evaluation and treatment of acute myocardial infarction complicating systemic lupus erythematosus. AB - Coronary artery disease has emerged as an important cause of death in young patients with SLE. We report three cases of acute myocardial infarction in young lupus patients who underwent emergent coronary angiography. One patient had a large coronary aneurysm and died five months later from myocarditis. The other two patients underwent coronary angioplasty. The difficulty in distinguishing coronary arteritis from premature atherosclerosis and its relevance to methods of treatment is discussed. PMID- 1735267 TI - Frequency and correlates of the saw-tooth pattern of flow-volume curves in an epidemiological survey. AB - The object of this report was to assess the possibility of identifying saw-tooth patterns on flow-volume curves in men aged 28 to 58 years. We studied the frequency of these patterns and their relationships with two indirect signs of UAO increase in FEV1/PEF and FEF50%/FIF50% ratios--as well as with clinical and functional data. Twenty-six of the 360 subjects surveyed, ie, 7.2 percent, had flow oscillations in the inspiratory and/or expiratory part of flow-volume curves, corresponding to the definition of the saw-tooth pattern. We observed significant relationships between the saw-tooth pattern and the mean FEV1/PEF ratio. In 97 subjects, the proportion of those with saw-tooth patterns was 13.4 percent, and the mean FEF50%/FIF50% ratio was 1.53 in those with the pattern vs 1.07 in those without it. These results show that the saw-tooth pattern was not rare in these men. PMID- 1735268 TI - Postthoracotomy respiratory muscle mechanics during incentive spirometry using respiratory inductance plethysmography. AB - We undertook this study to characterize the postthoracotomy compartmental displacement and respiratory mechanical changes occurring during and after the performance of the incentive spirometry maneuver. We also evaluated the effect of recumbency angle on compartmental recruitment. Sixteen patients were randomized to perform incentive spirometry either at 30 degrees or 60 degrees recumbency angle. They were studied using respiratory inductance plethysmography to measure tidal volume, respiratory frequency, inspiratory time, rib cage motion/tidal volume ratio, inspiratory duty cycle, and inspiratory flow. Patients were studied before surgery and on postoperative days 1 and 3. Statistical analysis was accomplished using multiple measures ANOVA with post-hoc Student's t-tests when appropriate. Preoperative incentive spirometry augmented VT by increasing both VT/TI and TI. Postoperatively, the incentive recruitment of VT was reduced, a result of a decrease in TI and TI/TTOT; VT/TI was unchanged. There was postoperative decrease of AB and AB/VT during incentive spirometry, greatest in the 60 degrees group. Our results characterize the nature of the respiratory recruitment afforded by incentive spirometry, before and after thoracotomy. We also found evidence of postthoracotomy diaphragmatic derecruitment during incentive spirometry exacerbated by a high recumbency angle. PMID- 1735269 TI - The relationship between airway responsiveness measured before and after the allergen-induced late asthmatic response. AB - Single blind allergen (Ag) and saline solution bronchial challenges were performed on two successive study days in ten asthmatic subjects. Histamine challenges were performed before, at approximately 2 h (or after resolution of the immediate bronchial response [IR]), and 24 h after saline solution or Ag inhalation. Specific airway conductance (SGaw) was measured after delivery of challenge agents until a 50 percent fall in SGaw was observed. The SGaw was monitored over 8 h for immediate and late asthmatic responses (LAR). Results were expressed as provocative concentrations eliciting a 50 percent decrease in SGaw (SGawPC50HIS). No significant changes from baseline SGaw or SGawPC50HIS were demonstrated after saline solution. Eight subjects (dual reactors) exhibited both an IR and LAR after Ag and two had isolated IRs. Of the eight dual reactors, five had greater than 50 percent decreases in SGawPC50HIS immediately after resolution of the IR and six exhibited such decrements 24 h after Ag provocation. Mean baseline SGawPC50HIS (N = 10) on the Ag challenge day was 3.2 +/- 4.59 mg/ml and decreased to 0.92 +/- 4.56 mg/ml at 102 to 187 minutes after Ag (p = 0.0009) and was significantly decreased from baseline at 1.47 +/- 3.8 mg/ml 24 h after Ag (p = 0.0004). One of the two patients with isolated IR also showed an early onset increase in airway responsiveness (EOR). There was a significant correlation between the percentage of fall from baseline in SGawPC50HIS immediately after the IR and that at 24 h after Ag (r = 0.811, p = 0.005). There was no significant correlation between the decrease in SGawPC50HIS after the IR and the magnitude of the LAR. These data suggest that (1) the early events occurring prior to the LAR may determine changes in airway responsiveness observed at 24 h after Ag challenge, and (2) the EAR to histamine is not exclusively associated with the LAR. PMID- 1735270 TI - A prospective study of community-acquired pneumonia in Hong Kong. AB - A prospective study of community-acquired pneumonia in Hong Kong was carried out between January and December, 1988. Ninety adults (57 male) with a mean age of 57.3 years were admitted to the Prince of Wales Hospital with community-acquired pneumonia. The etiologic diagnosis of pneumonia was made in 37 cases (41 percent). Pneumococcal infection was diagnosed in 11 patients (12 percent). The same number of patients had pulmonary tuberculosis presenting as acute pneumonia. It could not be differentiated from other causes of pneumonia on clinical and radiologic grounds, although pleural effusion and upper lobe involvement were more common in patients with tuberculosis. Chlamydia species were identified in five patients (6 percent) and Mycoplasma pneumoniae was identified in three patients (3 percent). There was no case of Legionnaires' disease. The etiologic agent could not be identified in 59 percent of cases. The low incidence of etiologic diagnosis of community-acquired pneumonia was probably related to the widespread use of antibiotics in private practice. Tuberculosis is an important cause of community-acquired pneumonia in Hong Kong and this diagnosis should be considered in patients who fail to respond to first-line antibiotics. PMID- 1735271 TI - Four-stage tuberculin testing in elderly subjects induces age-dependent progressive boosting. AB - We administered four sequential tuberculin skin tests (5 TU, PPD) with intervals of one week to 223 subjects older than 65 years of age to evaluate whether elderly subjects demonstrated progressive boosting. Indurations of at least 10 mm with increases of at least 6 mm (over the previous test) were considered significant reactions, and these were found in 29 percent of the subjects after test 1, in 43 percent after test 2, in 53 percent after test 3, and in 57 percent after test 4 (p less than 0.05), ie, only about 50 percent of all the positives were detected after the first test. The percentage of positive reactors was inversely related to age (p less than 0.001), yet this age-dependent difference decreased with increasing number of tests. For the 65- to 74-year-old age group, 44 percent reacted positively after the first test and after three tests almost a plateau of 65 to 70 percent positive reactors was reached, suggesting that a minority only of about 30 to 35 percent of these geriatric patients might have outlived their bacilli or were never infected. For the 75- to 84-year-old age group, 24 percent reacted after the first test and 55 percent reacted after the fourth one. For the older than 85-year-old age group, 19 percent positive reactors were found after the first test and 46 percent were found after the fourth test, without clear-cut leveling off toward a plateau value, suggesting that additional tests would induce further boosting. Mean diameters of positive reactions were 15 to 24 mm, and were mostly at least 12 mm larger than in the previous tests. These data support the hypothesis that the negative tuberculin reaction, which is often found in elderly subjects, is mainly due to the failing immune response to tuberculin antigen that can be restored progressively by repeated administrations. These findings, furthermore, emphasize that especially in elderly, care should be taken not to interpret a boosting reaction as a conversion and especially that neither a two-step testing as recommended by the ATS and CDC (Am Rev Respir Dis 1990; 142:723-35) nor even a four-step testing may suffice to detect all positives in this type of population. PMID- 1735272 TI - The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. AB - An abnormal chest roentgenogram is essential for the diagnosis of ventilator associated pneumonia. The diagnostic accuracy of various roentgenographic signs of pneumonia has not been assessed previously in the portable anteroposterior roentgenograms obtained in ventilated patients. Seven roentgenographic signs (air bronchograms, alveolar infiltrates, silhouette sign, cavities, fissure abutment, atelectasis, and asymmetric infiltrates superimposed on diffuse bilateral infiltrates) were evaluated for their accuracy in predicting pneumonia alone, in combination with other signs, or in combination with clinical parameters. The last roentgenogram prior to autopsy of 69 ventilated patients was interpreted by three reviewers and the above signs were correlated with autopsy evidence of pneumonia. Pneumonia was present in 24 (35 percent) of the 69 autopsies. No roentgenographic sign had a diagnostic efficiency of greater than 68 percent. By stepwise logistic regression, the presence of air bronchograms was the only roentgenographic sign that correlated with pneumonia in the total group, correctly predicting 64 percent of pneumonias. In patients without adult respiratory distress syndrome (ARDS), the presence of air bronchograms or alveolar infiltrates correlated with pneumonia, while in patients with ARDS, no roentgenographic sign and only the clinical parameter of purulent sputum correlated with pneumonia. Only a minority (7/22) of worsening alveolar infiltrates in all groups were due to pneumonia and were often confused with ARDS. Alveolar hemorrhage occurred with a surprising frequency (38 percent of autopsies), including 13/45 (29 percent) patients without pneumonia. Alveolar hemorrhage was associated with 29 percent of multiple air bronchograms and 30 percent of bilateral alveolar infiltrates in patients without pneumonia. We conclude that in intubated patients with diffuse bilateral roentgenographic infiltrates, no roentgenographic sign correlates well with pneumonia. No clinical parameter added to the accuracy of either an alveolar infiltrate or an air bronchogram in patients without diffuse infiltrates. Pulmonary hemorrhage and/or infarction are frequent autopsy findings in intubated patients and may be confused radiologically with pneumonia. PMID- 1735273 TI - Percutaneous dilatational tracheostomy. Results and long-term follow-up. AB - Ciaglia et al first reported percutaneous dilatational subcricoid tracheostomy in 1985. We are now reporting the results on 165 patients with follow-up on 52 patients who went on to decannulation. Our technique has been slightly modified and these points are emphasized. To date, there have been no significant perioperative or postoperative complications and no long-term complications on 52 patients who were followed clinically, postdecannulation, for from four months to five years. The procedure is recommended as simple, safe, and cost-effective. We feel it is the technique of choice for routine elective tracheostomy. PMID- 1735274 TI - Bronchoalveolar lavage in alcoholic liver cirrhosis. T-lymphocyte subsets and immunoglobulin concentrations. AB - The purpose of this study was to determine the phenotype profiles of immune effector cells and the concentrations of immunoglobulins in the lower respiratory tract of non-smoking patients with alcoholic liver cirrhosis (ALC). Nine nonsmoking patients with liver biopsy-proved ALC (grade B or C cirrhosis in Child's classification), free of clinical pulmonary symptoms, and with normal chest roentgenogram were included in the study. The control group included 12 healthy nonsmokers. Each patient had fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The number of T cells and of lymphocyte subpopulations was determined by immunofluorescence studies using monoclonal antibodies that were specific for CD3, CD4, and CD8 markers. Patients with ALC exhibited a dramatically increased percentage of CD8+ cells in BAL that induced a low CD4/CD8 ratio (0.96 +/- 0.15 vs 1.8 +/- 0.12 in healthy controls). Further characterization of lymphocyte subsets' dual immunofluorescence analysis demonstrated that most of the CD8+ alveolar lymphocytes had a phenotype of cytotoxic cells (CD8+ CD11b-; 48 percent +/- 13 in ALC vs 10 percent +/- 5 in controls). ALC was associated with an appreciable alveolar-capillary "leak" as demonstrated by a significant increase in BAL fluid albumin. In addition, the concentrations of immunoglobulins in BAL fluid were significantly greater in ALC than in controls. However, the relative (to albumin) coefficient of excretion of IgG, A, and M in and alpha 2-macroglobulin BAL fluid was not significantly different between controls and ALC. Our results indicate that increased proportions of CB8+ and especially of CD8+ CD11b- cells are a common feature in the lower respiratory tract of nonsmoking patients with ALC. These changes may be of potential functional importance in the regulation of the local pulmonary immune response in ALC. PMID- 1735275 TI - Pulmonary hypertension and human immunodeficiency virus infection. Two reports and a review of the literature. AB - Pulmonary hypertension may be primary (idiopathic) or secondary. While the etiologies for secondary pulmonary hypertension are diverse, infection with the human immunodeficiency virus (HIV) has not been included. To date there have been 16 reported cases of pulmonary hypertension in the HIV-infected population. Plexogenic arteriopathy was the most common pathologic finding. We report two HIV infected patients who were concomitantly found to have pulmonary hypertension with plexogenic arteriopathy. One patient had lymphocytic interstitial pneumonitis, an entity not previously associated with pulmonary hypertension. We review the 16 previous cases of pulmonary hypertension and HIV infection and discuss this association. PMID- 1735276 TI - Respiratory function in multiple sclerosis. Utility of clinical assessment of respiratory muscle function. AB - PURPOSE: The aim of this study was to assess the utility of clinical assessment of respiratory muscle weakness in MS. PATIENTS AND METHODS: We studied 40 MS patients who performed pulmonary function tests using standard procedures and measures of respiratory muscle strength. Descriptive clinical indices included a history of detailed neurologic findings, including upper and lower extremity weakness, cerebellar signs, and evidence of cerebral lesions and other clinical signs including dependence in activities of daily living, shortness of breath, weak voice, dysarthria and dysphagia. We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation. RESULTS: Mean values of TLC (95 percent +/- 14) VC (91 percent +/- 19), and RV (106 percent +/- 34) were normal. By contrast, MVV (68 percent +/- 20), PImax (74 percent +/- 27) and PEmax (51 percent +/- 22) were decreased. Stepwise multiple regression indicated that the best single predictor of expiratory muscle weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary ventilation accounted for 60 percent of the variance in PEmax. CONCLUSION: We conclude that clinical assessment is a better predictor of respiratory muscle weakness than spirometry and that a systematic clinical assessment supplemented by respiratory muscle assessment and MVV can uncover subtle respiratory muscle weakness in patients with MS. PMID- 1735277 TI - Oxygen uptake plateau during maximal treadmill exercise in children. AB - The leveling of oxygen uptake at high work loads has been utilized to define maximal VO2 during progressive exercise testing. Exercise studies in children have indicated, however, that a VO2 plateau can commonly be demonstrated in less than one half of subjects. To examine the potential contributions of subject effort, aerobic fitness, and nonaerobic performance to this variability, 15 children ages 7 to 10 years performed progressive treadmill walking to exhaustion with a ramp protocol. The VO2 plateau was defined as a change in VO2 during the final minute of exercise less than 2 SD below the mean of increases between the previous 4 to 5 submaximal minutes. Five subjects (33.3 percent) demonstrated a plateau. No significant differences in mean peak VO2, heart rate, or respiratory exchange ratio were observed between plateau and nonplateau groups. Testing results of speed (50-yard sprint) and leg power (vertical jump) were also similar. These findings suggest that following: (1) subject effort, aerobic fitness, and nonaerobic factors do not explain the presence or absence of a VO2 plateau during exercise testing of children; and (2) a VO2 plateau should not be used as a requirement for defining VO2max during treadmill testing in this age group. PMID- 1735278 TI - Infected radial artery pseudoaneurysms occurring after percutaneous cannulation. AB - During a ten-month period in 1988 at our institution, we identified three infected radial artery pseudoaneurysms (RAPAs) associated with arterial lines. A retrospective chart review to 1983 identified three additional cases, all occurring in 1986. In the six-year period of 1983 through 1988, during which approximately 12,500 radial artery catheters were placed, the incidence of RAPA formation was 6/12,500 (0.048 percent). Five of the six cases were associated with Staphylococcus aureus infection. The duration of radial artery cannulation was significantly longer in patients who developed a pseudoaneurysm (12.5 days) than in those patients who did not suffer this complication (4.3 days). Patients in whom infected RAPAs occurred also tended to be older (mean, 71.6 years) than the average age (54 years) for all patients admitted to the intensive care unit (ICU). They also tended to have long stays in the ICU prior to development of RAPA, the shortest stay being 11 days and the average being 51 days. Risk factors for the development of this complication may include advanced age, longer duration of catheterization and hospitalization, and infection with S aureus. PMID- 1735279 TI - A comparison of the effects of bid and qid dosing on compliance with inhaled flunisolide. AB - Noncompliance with inhaled steroids is a well-recognized problem in asthma therapy. We compared compliance with bid and qid regimens of inhaled flunisolide in 16 asthmatic subjects. Patients were instructed to take four inhalations bid for T1 to establish baseline compliance. During T2, half (group A) continued this dosing regimen, while the other half (group B) switched to two inhalations qid. Group A compliance did not significantly change from T1 to T2. The percentage of days with less than eight inhalations (underuse) for group B, however, increased from 20.2 +/- 40.3 in T1 (bid dosing) to 57.1 +/- 49.6 in T2 (qid dosing) (p less than 0.001). Concomitantly, the number of daily inhalations decreased from 7.9 +/ 2.5 to 6.8 +/- 3.1 (p less than 0.01). Reduced compliance with qid dosing was due in large part to an increase in frequency of six inhalations per day, resulting from tid use. Compliance with inhaled flunisolide, therefore, was worse with qid than bid dosing. PMID- 1735280 TI - Management of bacterial pneumonia in ventilated patients. Protected bronchoalveolar lavage as a diagnostic tool. AB - We conducted a prospective study to determine the effectiveness of protected bronchoalveolar lavage (PBAL) in diagnosing pneumonia in ventilated patients and the usefulness of bronchoscopic data in treating ventilated patients. Entrance criteria were (1) fever and a new or progressive infiltrate on chest roentgenogram with either leukocytosis or a macroscopically purulent tracheal aspirate, and (2) no antibiotic therapy for at least 48 h before bronchoscopy. Twenty-five ventilated patients met entrance criteria for the study and completed the protocol. PBAL was effective in retrieving distal airway secretions with a minimal degree of contamination as indicated by a specificity and a negative predictive value of 100 percent. Bacterial isolates grew in all patients with pneumonia at a concentration greater than or equal to 100,000 cfu/ml, with a median growth of 500,000 cfu/ml. The presence of a two-log difference between the highest quantitative culture count in patients without pneumonia and the lowest quantitative culture count in patients with pneumonia allowed a clearer determination of a patient's status, with regard to pneumonia, compared with the significant overlap in unprotected BAL. Gram and Giemsa stains of the PBAL were positive in all patients with pneumonia and negative in those without pneumonia. All but one patient with pneumonia received narrow-spectrum antibiotic therapy. All patients without infection had no antibiotic administered. Clinical and roentgenographic criteria could not discriminate between patients with and without pneumonia, confirming the findings of previous investigations. The results of microscopic and culture analyses of the PBAL effluent proved useful in directing antibiotic treatment in patients with pneumonia and in avoiding unnecessary antibiotic use in those patients without pneumonia. PMID- 1735281 TI - Veno-arterial carbon dioxide gradient in human septic shock. AB - Recent reports have shown that venous hypercarbia, resulting in a widening of the veno-arterial difference in PCO2 (dPCO2), is related to systemic hypoperfusion in various forms of low-flow state. Although septic shock usually is a hyperdynamic state, other factors can influence the CO2 production and elimination, and thus dPCO2 in septic shock This study examined the dPCO2 and acid-base balance together with cardiac output measurements and oxygen-derived variables in 64 adult patients with documented septic shock. For a total of 191 observations, a significant exponential relation between dPCO2 and CO was found. At time of first measurement, 15 patients had an increased dPCO2 (above 6 mm Hg) and a higher mixed venous PCO2 (PvCO2) (47.2 +/- 10.0 vs 35.9 +/- 7.3 mm Hg, p less than 0.001). These patients had a lower cardiac index (2.9 +/- 1.3 vs 3.8 +/- 2.0 L/min.m2, p less than 0.01), a higher oxygen extraction ratio, but a similar VO2 than patients with normal dPCO2. The higher dPCO2 could also be related to an impaired CO2 elimination as indicated by a higher PaCO2 and a lower PaO2/FIO2 in these patients. Nonsurvivors had a significantly higher dPCO2 than survivors (5.9 +/- 3.4 vs 4.4 +/- 2.3 mm Hg, p less than 0.05) in the presence of similar cardiac output. The higher dPCO2 in these patients was probably related to the higher blood lactate levels (7.7 +/- 5.3 mmol/L vs 4.5 +/- 2.8 mmol/L, p less than 0.01) and the more severe pulmonary impairment (SaO2 90 +/- 8 percent vs 95 +/- 4 percent, p less than 0.001). Arteriovenous oxygen content difference (dAVO2) and VO2 were similar in survivors and nonsurvivors. In conclusion, dPCO2 patients with septic shock is related principally to cardiac output but apparently also to the degree of pulmonary impairment. Although dPCO2 is larger in nonsurvivors, its prognostic value is modest. PMID- 1735282 TI - Nocturnal nasal intermittent positive pressure ventilation with bi-level positive airway pressure (BiPAP) in respiratory failure. AB - The purpose of this study was to assess the efficacy of bi-level positive airway pressure (BiPAP) ventilation through a nasal mask in the treatment of eight patients with hypoventilatory respiratory failure and nocturnal CO2 retention. Nocturnal CO2 retention was significantly reduced in all patients with the application of BiPAP during sleep (p less than 0.01). Daytime somnolence was relieved and dyspnea improved after three months of home BiPAP therapy. All patients tolerated home BiPAP therapy, and two patients who had previously been treated with volume ventilation via nasal mask found BiPAP more comfortable. There were no changes in FEV1 or FVC after three months of BiPAP. Daytime PaCO2 improved slightly or remained stable in all patients after three months of home BiPAP. BiPAP nasal ventilation is effective in reducing nocturnal CO2 retention short term in hypoventilatory respiratory failure due to obesity hypoventilation syndrome, chest wall restriction, or neuromuscular disease. Further studies in patients with COPD may be warranted. PMID- 1735283 TI - Oxygenation and ventilation during cardiopulmonary resuscitation utilizing continuous oxygen delivery via a modified pharyngeal-tracheal lumened airway. AB - Use of continuous transtracheal oxygen delivery systems combined with rhythmic chest compressions can provide excellent oxygenation and ventilation during cardiopulmonary resuscitation. However, occasional displacement of the transtracheal catheter results in life-threatening pneumomediastinal complications. We investigated using the pharyngeal lumen of a pharyngeal tracheal lumened airway (PtL) as an alternative delivery system for continuous oxygen flow in 21 large mongrel dogs. Excellent ventilation was possible in anesthetized, apneic, and paralyzed dogs in normal sinus rhythm from the "bellows" effect of chest compressions. The hypercapnia and respiratory acidemia resulting from 5 min of complete apnea in ten dogs during normal sinus rhythm was readily corrected (p less than 0.01). In an additional 11 dogs, external chest compressions were performed and oxygen was delivered continuously via the PtL during 20 min of ventricular fibrillation. During this period of cardiac arrest, pH declined (7.38 +/- 0.01 vs 7.19 +/- 0.02; p less than 0.01), but PaCO2 (35 +/- 1 vs 38 +/- 3 mm Hg) and PaO2 (67 +/- 2 vs 68 +/- 3 mm Hg) were not significantly different from prearrest values. Successful resuscitation was achieved in 8 of 11 (73 percent) animals, which is similar to the results in historical controls with endotracheal intubation. No pneumomediastinal complications were seen with use of the PtL. We conclude that using the pharyngeal lumen of the PtL for continuous delivery of oxygen combined with external chest compressions can provide a safe and effective mode of oxygenation and ventilation during cardiac arrest. PMID- 1735284 TI - Continuous negative extrathoracic pressure ventilation, lung water volume, and central blood volume. Studies in dogs with pulmonary edema induced by oleic acid. AB - The effect of continuous positive-pressure ventilation (CPPV) on extravascular lung water volume has been investigated, but there is only one report which studied the effect of continuous negative extrathoracic pressure ventilation (CNETPV). The effect of CNETPV on central blood volume (CBV) has not been studied. Changes in intrathoracic pressure by CNETPV may alter lung water volume and CBV. In this study the effects of CNETPV on lung water volume and CBV were compared with those of intermittent positive-pressure ventilation (IPPV) and CPPV in dogs with pulmonary edema induced by oleic acid. Nine mongrel dogs were anesthetized and given oleic acid at 0.06 ml/kg intravenously to induce pulmonary edema; CNETPV was applied with a cuirass and a negative thoracic pressure ventilator (Kimura OKT-100) for 1 h. Extravascular lung water volume (as extravascular thermal volume [EVTV]) and CBV were estimated with the double indicator dilution method using thermal-sodium; PEEP and continuous negative extrathoracic pressure were matched to produce the same increments in FRC. The EVTV increased during CNETPV but did not change during CPPV. The CBV decreased during CPPV but did not change during CNETPV. An increase of transmural pulmonary microvascular pressure was thought to be one of the reasons for the increase in EVTV with CNETPV. PMID- 1735285 TI - The clinical utility of postinfarction risk prediction. Performance perspective of electrophysiologic and other variables. PMID- 1735286 TI - Mechanisms of obstructive sleep apnea. AB - This article has reviewed the anatomic, compliance, reflex, and respiratory muscle variables that affect upper airway caliber and abnormalities which may precipitate upper airway collapse during sleep. One or more of these variables may be important in the mechanism of OSA in any given patient. First, anyone with anatomic narrowing of the upper airway is susceptible to OSA. However, we do know if anatomic narrowing of the upper airway is necessary for the development of OSA. Surely, heavy snoring produces pharyngeal trauma and possibly edema or inflammation, which in turn may narrow the upper airway. Submucosal adipose tissue or cervical adipose tissue may compress the airway when the tonic electrical activity of the pharyngeal muscles decreases with sleep onset. Data reviewed support the idea that the upper airway of OSA patients may be more collapsible than the upper airway of nonapneic subjects. Intrinsic tissue abnormalities have not been demonstrated that might be responsible for this collapsibility. Changes in collapsibility found are consistent with, and may be due to, changes in tonic and phasic contraction of upper airway muscles. Abnormalities in reflexes affecting upper airway size surely might exist in OSA. Edema or inflammation of pharyngeal tissues might not only narrow the upper airway but might also impair normal function of the receptors responsible for initiating protective reflexes. We propose the fluctuation between a low- and a high-drive state contributes to upper airway collapse in OSA. With this fluctuation the balance of forces and critical pressure concepts discussed above come into play (Fig 6). By stimulating upper airway inspiratory muscles, CO2 eliminates the hypoapneic, low-drive, high-resistance periods and thereby reduces the number of apneas. In addition, preferential stimulation of upper airway muscle activity dilates the upper airway per se. If the relative value of each of these factors can be determined diagnostically, perhaps therapy can be made more specific. By being more specific, therapy should be more successful than the present practice of prescribing a particular therapy, regardless of the specific mechanism responsible for the OSA in a given patient. PMID- 1735287 TI - Contemporary clinical trials in acute respiratory distress syndrome. PMID- 1735288 TI - An asymptomatic hilar mass. PMID- 1735289 TI - Ceftazidime monotherapy for pulmonary melioidosis in a traveler returning from Thailand. AB - A patient with deteriorating pulmonary melioidosis rapidly recovered after treatment with ceftazidime. To prevent possible relapses, an oral maintenance regimen of amoxicillin and clavulanic acid was prescribed for a period of three months. Melioidosis is caused by Pseudomonas pseudomallei. It is an insidious disease because of its variable clinical presentation, possible long-term asymptomatic carriage, broad-spectrum resistance to first-line antibiotics, and high mortality rate. As in our patient, the diagnosis should be particularly considered when there is reduced immunologic resistance and previous exposure in endemic areas, such as Southeast Asia. PMID- 1735290 TI - Problem of management of obstructive cardiomyopathy. PMID- 1735291 TI - Pulmonary edema as a radiologic manifestation of venous air embolism secondary to dental implant surgery. AB - Three serial cases of fatal venous air embolism were reported after mandibular prosthetic dental surgery. Initially attributed to anesthetic factors, the deaths resulted from intraosseous irrigation with coolant tap water and air. Pulmonary edema was seen on chest roentgenograms and might have suggested the cause of death. PMID- 1735292 TI - An artifact induced by negative pressure ventilation. AB - This report draws attention to an artifact that influences the qualitative information gained from respiratory inductance plethysmography during negative pressure ventilation with a cuirass. This artifact may prevent identification of upper airway obstruction, a manageable complication of this mode of ventilation. PMID- 1735293 TI - Continuous murmur in Lutembacher syndrome analyzed by Doppler echocardiography. AB - A continuous murmur was heard in a 47-year-old woman with Lutembacher syndrome. Transesophageal and intraoperative Doppler echocardiography revealed the murmur originating from the accelerated blood flow passing through the small atrial septal defect. To our knowledge, this is the first reported case of a continuous murmur in Lutembacher syndrome analyzed by Doppler echocardiography. PMID- 1735294 TI - Pneumococcal crepitant cellulitis caused by a bronchocutaneous fistula. AB - An elderly woman who had received radiation treatment for carcinoma of the lung presented with erythema, crepitus and pain over the scapular area. Streptococcus pneumoniae was isolated in pure culture from the subcutaneous tissues, and a bronchocutaneous fistula was demonstrated. PMID- 1735295 TI - Inadvertent loss of bronchoscopy instruments in the tracheobronchial tree. AB - Equipment malfunction is a rare complication of flexible fiberoptic bronchoscopy. We report an unusual example of equipment failure resulting in the inadvertent introduction of a foreign body (the tip of a cleaning brush) into the bronchial tree of a patient during FFB. In addition, we review several other cases in which problems have been caused by malfunction of accessory equipment. Careful inspection of all cleaning and biopsy utensils should reduce the chance of iatrogenically introducing a foreign body from the bronchoscope channel into the patient's airway. We suggest that biopsy forceps are the best retrieval instrument to use when the foreign body involved is a brush or a piece of wire. PMID- 1735296 TI - Reversible pulmonary artery obstruction in a patient with bronchogenic carcinoma. Diagnosis by two-dimensional and Doppler echocardiography. AB - Neoplastic invasion of the pulmonary arteries, although common, rarely results in obstruction to right ventricular outflow. We report an unusual case of severe pulmonary hypertension, right ventricular dilatation, and righ ventricular dysfunction resulting from pulmonary arterial compression by bronchogenic carcinoma. The diagnosis was made by two-dimensional and Doppler echocardiography and supported by computed tomographic findings. Echocardiography was used to follow the patient's response to therapy and documented the subsequent resolution of pulmonary arterial obstruction. PMID- 1735297 TI - Chylous transport of amiodarone. AB - A patient receiving amiodarone for longstanding ventricular dysrhythmias presented with idiopathic chylothorax. During drainage of chylothorax for pleurodesis, serial plasma amiodarone concentrations declined while pleural fluid concentrations remained stable. Chylous transport of amiodarone and other lipid bound drugs should be recognized to avert complications during chylothorax drainage. PMID- 1735298 TI - Pulmonary manifestations of Staphylococcus aureus septicemia. AB - This study includes 140 episodes (138 cases) of Staphylococcus aureus septicemia, made up mostly of community-acquired, nonintravenous drug abuse (nonIVDA) cases. Unlike other series, injury wounds and skin or soft tissue infections were the most common sites of primary infection. In spite of a different patient population and lack of cases with tricuspid valvular endocarditis, the lungs were still the most common site of secondary infectious foci and most developed within two weeks of onset of the septicemia. PMID- 1735299 TI - Aspiration injury due to polyacrylamide. AB - Acute lung injury secondary to aspiration of polyacrylamide, a synthetic polymer used widely in industry, has not been previously described in man or animal. We report the case of a 26-year-old man who aspirated polyacrylamide gel while cleaning it out of a tank truck. Subsequently, severe airway obstruction and lung parenchymal damage developed, and the patient died. At autopsy, numerous polyacrylamide particles were found in the lungs, along with extensive bronchiolar and alveolar damage. PMID- 1735300 TI - Unruptured congenital aneurysm of the left sinus of Valsalva presenting as acute right ventricular failure. AB - A patient with unruptured congenital aneurysm of the left coronary sinus of Valsalva presented with acute right-sided heart failure due to right ventricular outflow tract obstruction. The mechanism for such an acute presentation may have been a sudden increase in the size of the aneurysm. The surgical importance of this lesion is the combined aortocameral approach which is seldom required for correction of such aneurysms. PMID- 1735301 TI - Respiratory failure and cor pulmonale associated with tracheal mucoid accumulation from a SCOOP transtracheal oxygen catheter. AB - Transtracheal oxygen (TTO) delivery for patients with chronic hypoxemia has been used increasingly since its introduction in 1982. Most complications have been relatively minor and usually occur in conjunction with catheter placement. This report describes two patients with long-term catheter use who developed increasing respiratory failure and cor pulmonale, at least in part, due to a large tracheal mucus plug. PMID- 1735302 TI - Transmission of tuberculosis to hospital workers by a patient with AIDS. AB - A patient with acquired immunodeficiency syndrome (AIDS) was admitted to a hospital with cough and fever and after 29 days was transferred to a hospice. He was eventually shown to have active pulmonary tuberculosis. This diagnosis was obscured clinically by simultaneous infection with Pneumocystis carinii and Mycobacterium avium complex (MAC). Laboratory recognition of Mycobacterium tuberculosis was delayed because of overgrowth of cultures by MAC but was later established using DNA probe techniques. Thirty (19 percent) of 158 health care workers who had been exposed to this patient had conversion of their tuberculin skin tests. Diagnostic difficulties and nosocomial transmission of tuberculosis may occur when patients with AIDS have mixed mycobacterial infections. PMID- 1735303 TI - Nontraumatic acute anterior mediastinitis in two HIV-positive heroin addicts. AB - We present the cases of two young heroin addicts seropositive for HIV who had life-threatening spontaneous acute anterior mediastinitis due to Staphylococcus aureus. This was the consequence of the spreading to the mediastinum of an infection of the chest wall. Complete cure was achieved with antibiotics and surgical drainage. Spontaneous mediastinitis should arouse suspicion of the possibility of HIV infection. PMID- 1735304 TI - Steroid-responsive alveolitis associated with ulcerative colitis. PMID- 1735305 TI - Complex cryptococcal empyema. AB - Cryptococcus neoformans continues to present diagnostic and treatment challenges in patients with underlying malignant neoplasms. Cryptococcal empyema is a relatively rare complication of cryptococcal disease. It is important to distinguish whether uncontrolled malignancy or cryptococcal infection is responsible for the effusion. We used traditional diagnostic approaches, bronchoscopy and transthoracic fine needle aspiration, to verify the presence of the organism but continued to have treatment failure until adequate drainage was established. PMID- 1735306 TI - Pulsus paradoxus in anaphylactic shock due to urokinase administration. PMID- 1735307 TI - On being fair to the pulmonary artery catheter. PMID- 1735308 TI - Contents of chest wall cold abscess flowing into the epidural space in miliary tuberculosis. PMID- 1735309 TI - Arterial or venous? You make the call. PMID- 1735310 TI - Sexism or satire? Response to a special communication. PMID- 1735311 TI - Tissue invasion by Mansonella ozzardi in a patient with adenocarcinoma. PMID- 1735312 TI - Multifactorial index of preoperative risk factors in colon resections. AB - Our aim was to analyze the predictive value of a variety of preoperative risk factors on operative outcomes. We reviewed all colorectal resections performed in a single hospital between January 1985 and May 1990. Nine hundred seventy-two resections were performed on 825 patients. We studied 17 preoperative risk factors generated from various medical risk categories. Using the multivariate discriminant function analysis, we calculated that 11 of the 17 risks were of significance in predicting outcomes (all with P less than or equal to 0.031). These factors included emergent operation, age greater than or equal to 75 years, congestive heart failure (CHF), prior abdominal or pelvic radiation therapy, corticosteroid use, albumin less than 2.7 g/dl, chronic obstructive pulmonary disease (COPD), previous myocardial infarction (MI), diabetes, cirrhosis, and renal insufficiency. The classification function generated by the discriminant analysis was used to categorize patients into one of four risk groups depending on their "risk score." The index used to develop each patient's "risk score" ranged from six points for an emergency operation to one point for diabetes. The mortality rates for the various risk groups were as follows: Group 1, zero to four points, 1 percent; Group 2, five to eight points, 10 percent; Group 3, 9 to 13 points, 19 percent; Group 4, greater than 13 points, 33 percent. In contrast to previous reports, we showed that age greater than or equal to 75 years alone is not a major preoperative risk factor but, rather, acts as a modifier for the other predictors of postoperative complications. We then assessed clinical questions concerning specific preoperative risks, such as steroid use, obesity, inflammatory bowel disease, COPD, and prior laparotomy, and their associated specific postoperative complications and have developed prevention strategies based on these findings. Through the use of the risk index, we also were able to assess an individual patient's operative risk more accurately. PMID- 1735313 TI - Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). AB - A randomized, controlled trial of adjuvant immunochemotherapy with PSK (Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK group received PSK orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow up time for this study was four years (range, three to five years). The disease free survival curve and the survival curve of the PSK group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival, P = 0.013; survival, P = 0.013). These results indicate that adjuvant immunochemotherapy with PSK was beneficial for curatively resected colorectal cancer. PMID- 1735314 TI - Conservative surgery for early cancer of the distal rectum. AB - From 1967 through 1988, 36 patients underwent local excision of a distal rectal cancer as an initial operative procedure with curative intent. A diagnostic, preoperative protocol was performed to assess the histologic grade of the tumor, the depth of penetration in the rectal wall, and the presence of positive lymph nodes or distant metastases. All patients had a transanal local excision performed under general anesthesia. If preoperative criteria were not confirmed by histopathologic specimen examination, a major operation was advised. To increase the chance of local control, external adjuvant radiotherapy was used in T2 cancers. Postoperative mortality was 0 percent. The postoperative complication rate was 9.3 percent. The observed local recurrence rate was 3 percent, and the rectal cancer-specific death rate was 6 percent. We compared these results with those obtained in 70 concomitant patients operated on by us employing a traditional resection for Dukes' A rectal cancer. There are no statistically significant differences between groups. In light of our findings, a policy of curative local excision is justified in accurately selected cases of distal rectal cancer. PMID- 1735315 TI - Influence of sleep on anal sphincteric pressure in health and after ileal pouch anal anastomosis. AB - Fecal incontinence at night may be a disturbing consequence of ileal pouch-anal anastomosis (IPAA). The hypothesis was that decreases in anal canal resting pressure occur as sleep deepens and that the decreases are more profound in pouch patients with incontinence than in controls. Using a sleeve catheter assembly for recording intraluminal and canal pressure and polysomnographic recordings of sleep stages, progressive decreases in anal canal resting pressure with deepening sleep occurred in 11 healthy controls (mean +/- SEM: 57 +/- 3 mm Hg to 43 +/- 3 mm Hg: P less than 0.05) and in 11 patients after IPAA (55 +/- 3 mm Hg to 42 +/- 4 mm Hg; P less than 0.05). Minute-to-minute variations in mean pressure were also found in both controls and IPAA patients, and they were greater at night in patients (P less than 0.05), except during rapid eye movement (REM) sleep. In three patients, resting pressure during REM sleep decreased markedly to 31 +/- 8 mm Hg. This decrease plus the variations in pressure during REM sleep led to incontinence. In conclusion, decreases in anal resting pressure coupled with marked minute-to-minute variations in pressure during sleep occurred in controls and in patients after IPAA and, when profound, led to nocturnal fecal incontinence in some patients. PMID- 1735316 TI - Effect of intraoperative radiation on the tensile strength of small bowel anastomoses. AB - Increasing interest in the use of preoperative or intraoperative radiation therapy for cancer has led to concerns regarding tissue healing and integrity subsequent to treatment. This is especially so for intestinal anastomoses incorporating irradiated bowel, where poor healing may lead to anastomotic disruption and sepsis. One hundred thirty Sprague-Dawley rats were randomized into five groups as follows: both limbs, one limb, or neither limb of an anastomosis received 2,000 R of radiation intraoperatively. A fourth group had a segment of small bowel irradiated, with no anastomosis; a fifth group had the gut exposed by celiotomy. The control groups and all anastomoses underwent tensile strength measurements on the seventh postoperative day, with findings as follows: no anastomosis, no irradiation, 143.75 g; no anastomosis, irradiated, 114.50 g; anastomosis, no irradiation, 85.273 g; anastomosis, one limb irradiated, 78.100 g; anastomosis, both limbs irradiated, 59.00 g. There was no statistical difference in tensile strength of the anastomosis between when neither limb and when just one limb was irradiated. However, when both limbs were irradiated, the loss of strength was statistically significant (P = 0.002). Irradiation damage scores were assigned using Black et al.'s histologic scoring system. These scores were not significantly different between the irradiated segments. Inflammation and fibrosis scores for the anastomoses were also not significantly different. These results indicate that, in rats, anastomotic healing is impaired only when both limbs of the anastomosed intestine are irradiated. The normal strength of the anastomosis with only one limb irradiated cannot be explained by differences in inflammation, fibrosis, or radiation damage and is caused by an undetermined factor. PMID- 1735317 TI - Partial colectomy and coloanal anastomosis for idiopathic megarectum and megacolon. AB - Adult patients with an idiopathic megarectum or megacolon can experience severe constipation requiring surgical treatment. Some of these patients have a proximal colon of normal diameter, with dilatation involving only the left or distal colon and rectum. The results of partial colonic and rectal resection with coloanal anastomosis in such patients have been reviewed. Seven patients (two female and five male) underwent a coloanal anastomosis over a seven-year period. The median age at operation was 19 years, the mean age at onset of symptoms was five years, and the mean follow-up period was one year. Five patients experienced a return to normal bowel frequency with the loss of most symptoms. One patient has an ileostomy because of persistent constipation after the procedure. One subject died because of postoperative bleeding from the anastomosis and subsequent cardiac and respiratory complications. This operation may have a place in the treatment of severe constipation caused by idiopathic megarectum and megacolon, but careful preoperative motility studies and meticulous attention to operative technique are required for a good outcome. PMID- 1735318 TI - Immunocytochemical analysis of receptors for estrogen and progesterone in fine needle aspirates from anal epidermoid carcinoma. AB - Fifteen patients with anal epidermoid carcinoma were examined with percutaneous or transanorectal fine needle aspiration (FNA) cytology. Aspirates from all patients allowed cytologic verification of the diagnosis. Estrogen receptor (ER) and progesterone receptor (PgR) were analyzed using an immunohistochemical technique well adapted for steroid receptor analysis in hormone-dependent carcinomas. Neither ER nor PgR could be detected in any of the aspirates. This finding is somewhat unexpected since there is a strong female predominance in this tumor type. However, our findings do not negate that sex steroid hormones may indirectly play a role in the tumorigenesis of anal epidermoid carcinoma. PMID- 1735319 TI - Newly designed occluder pin for presacral hemorrhage. AB - Conventional hemostatic measures are often unsatisfactory in presacral venous bleeding occurring during surgical mobilization of the rectum. We designed a new type of hemorrhage occluder pin, with a ridged shaft, which may be rapidly placed into the sacrum to control hemorrhage. The aims of this study were 1) to assess the best pin shaft length by measuring the thickness of human sacral vertebral bodies, 2) to measure the forces needed to pull the newly designed pin out of the human sacrum compared with conventionally shaped titanium thumbtacks, and 3) to assess clinically the efficacy of the new device. Four fresh cadaveric pelves were isolated and cut on a sagittal plane, and the thickness of each vertebral body was measured. Titanium pins, both with ridged and with smooth shafts, were used. Twelve-millimeter-shaft pins were used for S1 and S2, and 7-mm pins were used for S3, S4, and S5. Pins were inserted into each sacral vertebra, and the forces needed to extract them from the bone were measured by computerized dynamometry. Significantly more force was required to extract ridged vs. smooth pins, both with 12-mm and with 7-mm shafts. There was no significant difference between the forces needed to pull out 12-mm vs. 7-mm pins. The new pin was successfully used to stop presacral hemorrhage in three patients with no complications one, three, and six months after surgery. This newly designed hemorrhage occluder pin may represent an improved method of controlling presacral venous hemorrhage. PMID- 1735320 TI - Influence of myectomy, ileal valve, and ileal reservoir on the ecology of the ileum. AB - Fecal bacteriology, fecal volatile fatty acids, and ileal mucosal morphology were studied in dogs after ileoanal anastomosis alone, ileoanal anastomosis and myectomy, ileoanal anastomosis and myectomy with ileoileal valve, and ileoanal anastomosis with duplicated (J) ileal reservoir. The ratio of anaerobes to aerobes was significantly less in stool from dogs which had undergone ileoanal anastomosis compared with each of the other three groups (P less than 0.01). The numbers of streptococci and clostridia both were significantly less in stool from dogs with ileoanal anastomosis alone than in any other group. The concentrations of fecal acetic and propionic acids were significantly less in dogs with ileoanal anastomosis alone than in any other group (P less than 0.05), but there were no significant differences in the concentrations of fecal butyric or valeric acids. The severity of mucosal inflammation and degree of villous atrophy were more marked in the ileum of J reservoirs (P less than 0.01), and the percentage of stool retained after defecation was greater (P less than 0.05) in dogs with J reservoirs than in any other group. Therefore, the use of myectomy resulted in significant changes in the ecology of the distal ileum although changes typical of pouchitis were seen only in dogs with J reservoirs. PMID- 1735321 TI - Diminutive colonic polyps: an indication for colonoscopy. AB - A prospective study investigated the significance of solitary diminutive colonic polyps discovered during screening flexible sigmoidoscopy. Eighty-two patients with a solitary diminutive polyp (less than or equal to 5 mm) underwent colonoscopy after cold biopsy of the index polyp. Of the patients with adenomatous index polyps, 42.5 percent had proximal neoplastic polyps. Of the patients with hyperplastic index polyps, proximal neoplastic polyps were found in 38.9 percent. These data suggest that diminutive polyps identified during flexible sigmoidoscopy, whether adenomatous or hyperplastic, place the patient in the intermediate risk group for colorectal neoplasia. We recommend that any patient with polyps seen during screening sigmoidoscopy, regardless of histopathology, should undergo colonoscopy. PMID- 1735322 TI - Does a proximal colostomy affect colorectal anastomotic healing? AB - Fecal diversion has been implicated as an etiologic factor in anastomotic stenosis following colorectal surgery, particularly following the use of circular anastomotic stapling devices. However, experimental confirmation of the effects of fecal diversion on anastomotic healing is virtually nonexistent. The purpose of this study was to serially evaluate colorectal anastomotic healing with proximal colostomy (COL) and without it (CON; control) using two anastomotic techniques in a porcine model. Fifty-two (28 CON; 24 COL) mixed-breed female pigs had colorectal anastomoses using either a two-layer hand-sewn (HS) or an EEA (U.S. Surgical Corporation, Norwalk, CT) circular stapled (CS) technique. Anastomotic blood flow was measured using laser Doppler velocimetry (LDV). At second surgery (5, 11, 60, or 120 days postoperatively), the following data were collected: repeat LDV, gross and microscopic anastomotic inflammatory scores, anastomotic diameter, and bursting pressure. There were no significant differences in anastomotic blood flow (LDV), inflammatory scores, or incidence of leak or stenosis between the CON and COL groups or between anastomotic techniques. Bursting pressure was significantly lower for the COL group at day 11 but not any other postoperative day (POD). Proximal colostomy does not appear to exert adverse effects on colorectal anastomotic healing. The choice of colorectal anastomotic technique should not be influenced by the need for proximal colostomy. PMID- 1735323 TI - Trend of large bowel tuberculosis and the relation with pulmonary tuberculosis. AB - From 1965 to 1989, 60 cases of large bowel tuberculosis among 116 cases of abdominal tuberculosis are reviewed and analyzed. Lesions located in the cecum or ileocecal region were found in 49 of the 60 cases. Most of the patients (50/60) received surgical intervention, but the definite diagnoses had never been proved until surgery. The diagnoses were proved by histopathologic examination in these 50 cases. Antituberculosis medications were given for at least nine months in all patients. Twenty-nine of the 50 patients who received operations had primary anastomosis during the operations, and no leakage occurred. Evidence of pulmonary tuberculous lesions could be found in 40 of the 60 cases. Positive findings of tubercle bacilli in sputum smear or culture were noted in 13 cases. The positive rate of sputum examinations decreased during 1980 to 1989; 25.6 percent (10/39) were positive from 1965 to 1979 and 14 percent (3/21) were positive from 1980 to 1989. In the meantime, there was a steady decline in the cases of large bowel tuberculosis in the most recent few years. An antituberculosis program has been carried out in the past 40 years with remarkable effect in the Taiwan area, but the possibility of intestinal tuberculosis still exists. The authors suggest that surgeons keep tuberculosis in mind when they are dealing with patients who suffer from intestinal obstruction of unknown origin with the suspected findings of pulmonary tuberculosis in chest x-ray films. PMID- 1735324 TI - Arterial thromboembolic complications of inflammatory bowel disease. Report of three cases. AB - Extraintestinal manifestations of inflammatory bowel disease are legion and are demonstrated in one-third of those afflicted. In general, they do not mandate surgery. Three patients with active pancolonic ulcerative colitis developed arterial thromboembolic complications prior to surgical treatment. Thromboembolic complications are not fully understood, as is evidenced by the paucity of information in the literature, and only sporadic cases of arterial thromboemboli are found. These have been described primarily in the postsurgical patient. To ascertain whether others have encountered similar cases, a survey form was distributed to members of The American Society of Colon and Rectal Surgeons, yielding an additional 54 patients with thromboembolic complications. Approximately two-thirds were deep venous thromboses and/or pulmonary emboli. Ten patients had cerebrovascular accidents, and eight had arterial emboli. Eleven patients, over 21 percent, suffered multiple events. There were four resultant mortalities. An arterial thromboembolic event in a patient with ulcerative colitis is usually associated with pancolonic disease, has a poor long-term prognosis, and is an indication for colectomy. PMID- 1735325 TI - Multiple colorectal neoplasms in a young adult with hypogammaglobulinemia. Report of a case. AB - We report on a 22-year-old man with congenital hypogammaglobulinemia who developed multiple colorectal neoplasms. An immunodeficiency had been diagnosed in the patient since two years of age, and this time many tumors of the sigmoid colon and rectum were detected by barium enema and fiberscopy. Abdominoperineal resection was performed, and the resected specimen revealed 29 polyps, including 9 adenocarcinomas and 20 adenomas. The carcinomas, measuring 0.8 to 11.0 cm in size, showed various depths of invasion, and the adenomas, measuring 0.2 to 1.5 cm in size, showed various degrees of epithelial atypia. DNA analysis demonstrated that the tumors were heterogeneous, showing different DNA index and ploidy patterns. The pathogenetic relation between malignancy and immunodeficiency is also reviewed. PMID- 1735326 TI - "House" advancement pedicle flap for anal stenosis. AB - Long strictures of the anal canal, extending from the dentate line to the perianal skin, have challenged surgeons for many years. Numerous techniques have been devised to treat anal strictures. A technique to relieve an anal stenosis that involves the entire circumference and the length of the anal canal from the dentate line onto the perianal skin is described. It has two principal advantages: 1) it provides a broad skin flap for the entire length of the involved anal canal; and 2) it provides primary closure of the donor site. In addition, it avoids extensive mobilization of tissue, the flap maintains good blood supply with minimal tension, and there is no small tip prone to necrosis. PMID- 1735327 TI - Local excision of rectal tumors: specimen orientation. AB - Transanal local excision is a management option for patients with rectal tumors. An important final step in this operation is specimen orientation. A simple technique is described for specimen preparation, ideally performed by the surgeon in the operating room. This technique is recommended as the concluding step, for it can be as important as the local excision itself in regard to the determination of adequacy of resection and the need for additional treatment. PMID- 1735328 TI - Practice parameters for the management of anal fissure. The Standards Task Force American Society of Colon and Rectal Surgeons. AB - It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient. PMID- 1735329 TI - A scoring system for diagnosing irritable bowel: time to try again? PMID- 1735330 TI - Irritable bowel syndrome. Still far from a positive diagnosis. AB - The diagnosis of irritable bowel syndrome requires the exclusion of any associated organic disease: a positive diagnosis would avoid expensive and potentially dangerous diagnostic procedures. A scoring system has been proposed for positive diagnosis where more than 44 points excluded organic digestive disease. The aim of this study was to determine the usefulness of this scoring system in a different setting. Patients (1257) consecutively referred to our medical division were admitted to the study and 270 of these, complaining of abdominal symptoms, were scored on the Kruis system method. The positive predictive value (53.8% for men and 81.5% for women) and the sensitivity (46.7% and 59.5%) did not appear to be adequate. The negative predictive value (91.6% and 87.3%) and the specificity (93.5 and 95.4%) gave higher results, but two cases of neoplasia and nine cases of other organic digestive diseases were not identified or suggested. We believe that this scoring system may be useful only as a first step in a diagnostic flow chart. PMID- 1735331 TI - Enteric and central contributions to intestinal dysmotility in irritable bowel syndrome. AB - The aim of the study was to further elucidate the pathophysiology of irritable bowel syndrome and its subgroups by examining and comparing alterations in small bowel motility, specifically phase II and phase III components of the migrating motor complex. Prolonged recordings of interdigestive small bowel motility were obtained during both diurnal and nocturnal periods in 20 patients with irritable bowel syndrome--10 with predominant constipation and 10 with predominant diarrhea -and in 10 healthy subjects. Diurnal amplitude (mean +/- SD) of phase III activity fronts was lower (P less than 0.05) in constipation-predominant patients (16.3 +/- 3.1 mm Hg) than in diarrhea-predominant patients (20.2 +/- 3.1) or controls (20.9 +/- 2.7). Similar findings were observed nocturnally. Phase III cycle length was also significantly prolonged diurnally in constipation predominant patients when compared to the other groups. In the diarrhea predominant group repetitive and rapidly propagated bursts of contractions were observed in eight patients, and this pattern occupied a significantly greater proportion of phase II motor activity than in controls. These alterations in phase II and in phase III components of the migrating motor complex suggest that both local (enteric) and more central mechanisms may operate to produce intestinal dysmotility in the irritable bowel syndrome and that these mechanisms differ according to the predominant alteration of bowel habit. PMID- 1735332 TI - Functional adaptation of rat remnant colon after proximal hemicolectomy. AB - Functional adaptation of the remnant intestine after extensive resection of small bowel is well documented. The effects of partial resection of large bowel on the remaining colon have not been characterized. Transepithelial potential (VT), tissue resistance (RT), and short-circuit current (Isc) were measured in vitro across distal colonic tissue of rats three weeks after proximal hemicolectomy with ileotransversotomy and compared to the same parameters measured in the distal colon of control animals. In a second series of experiments, an in vivo perfusion technique was used to measure changes in sodium, potassium, and water transport in distal colon following proximal hemicolectomy. A 2.5-fold increase in VT (P less than 0.01), a 62% increase in RT (P less than 0.001), and a 35% increase in Isc (P less than 0.05) were observed three weeks following hemicolectomy when compared to control animals. A 64% increase in net sodium absorption (P less than 0.025), no significant change in net potassium transport, and a 115% increase in net water absorption (P less than 0.01) were demonstrated in hemicolectomized animals when compared to control. It is concluded that in the rat the distal colon is capable of functional adaptation to increase net sodium and water absorption within three weeks after proximal hemicolectomy. The mechanism responsible for this adaptive process has yet to be defined. Our findings may explain the lack of chronic diarrhea in patients undergoing right hemicolectomy. PMID- 1735333 TI - Association of constipation with neurologic diseases. AB - To investigate possible etiologic influences on the development of constipation, the present study examines the concordant occurrence of constipation with other diseases. Using 8.8 million Medicare patients hospitalized in the United States during 1987, the frequency distribution of all three-digit International Classification of Diseases (ICD) codes was compared in constipated patients and patients without constipation. Most associations and the closest associations were observed between constipation and neurologic diseases, the majority of which resulted from damage to the central nervous system. Associations between constipation and disorders of the spine also involved neuronal damage. The influence of potential confounding factors such as immobility or pain on the development of constipation was assessed and found to be minimal. The frequent association of constipation with disorders involving neuronal malfunction suggests that disruption of the neural modulation of colonic motility may play an important role in the development of constipation. PMID- 1735334 TI - Gut hormones and gastrointestinal motility in children with cystic fibrosis. AB - Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis. PMID- 1735335 TI - Short-chain fatty acids do not alter jejunal motility in man. AB - Short-chain fatty acids (SCFAs) alter ileal and colonic motility, but their effects on duodenojejunal motility are unknown. Simultaneous jejunal manometric recordings and hydrogen breath tests after lactulose were performed in eight healthy subjects during continuous duodenal infusion of either saline or SCFAs. These experiments were conducted in the fasting state and postprandially. The effects of various boluses of SCFAs on duodenojejunal motility were also determined in six subjects. During the fasting period, the number and characteristics of migrating motor complex, prolonged propagated contractions, discrete clustered contractions, motility index, and orocecal transit time were similar during saline and SCFAs. Similarly, the motility index and the duration of the postprandial period were not different between SCFAs and saline after the meal. The motility index was significantly increased after each of the 100-ml boluses (saline or SCFAs), but was not altered after the 12.5-ml boluses, suggesting a volume-related effect. Thus, SCFAs do not seem to affect proximal small bowel motility in healthy humans. PMID- 1735336 TI - Effects of the prodrug loperamide oxide, loperamide, and placebo on jejunal motor activity. AB - This crossover, double-blind study investigated the effects of single oral doses of the prodrug loperamide oxide, which is reduced gradually to loperamide in the intestine, and loperamide on jejunal motor activity in 12 fasting healthy men. Five minutes after a phase III of the migrating motor complex (MMC), 2 mg loperamide oxide, 4 mg loperamide oxide, 4 mg loperamide, or placebo were administered. Thereafter, motor activity 10-30 cm abroad the ligament of Treitz was recorded with five catheter orifices at 3-cm intervals over 4 hr. Number of contractions and area under curve increased significantly with 4 mg loperamide and 4 mg loperamide oxide, the increases with loperamide oxide occurring more gradually. Placebo and 2 mg loperamide oxide had no discernible effects. With both 4 mg loperamide and 4 mg loperamide oxide, phase I of the MMC was slightly prolonged and phase II and the time from drug administration to the onset of the first phase III slightly shortened. The percentage of aborally propagated contractions in phase II increased with all active treatments, whereas the occurrence of phases III was not altered. PMID- 1735337 TI - Mucosal protective effects of vitamin E and misoprostol during acute radiation induced enteritis in rats. AB - Cytotoxic effects of ionizing radiation on gastrointestinal epithelium may be mediated by oxygen free radicals. Therapeutic intervention directed toward oxidant scavenging and increasing tissue oxygen tension may provide a novel approach to management. We investigated the effects of a nonenzymatic oxygen radical scavenger (vitamin E) and an exogenous PGE1 analog known to increase mucosal blood flow (misoprostol) on acute radiation enteritis. Rats were pretreated with: (1) vitamin E, (2) misoprostol, or (3) a combination of both agents prior to 10 Gy abdominal radiation. Three days following irradiation, net fluid absorption using in vivo isolated loops, mucosal histology, and mucosal morphometry using a computerized videoplan were determined in jejunum, ileum, and colon. Nonirradiated control intestine demonstrated net fluid absorption in all segments, which was not altered by vitamin E and/or misoprostol treatment. Irradiation significantly reduced net fluid absorption in jejunum, ileum, and colon. Vitamin E administered prior to irradiation maintained jejunal, ileal, and colonic fluid absorption near control levels. In contrast misoprostol or a combination of vitamin E and misoprostol did not provide protection against the injury caused by abdominal irradiation. Alterations in intestinal fluid absorption occurred without significant changes in histologic or morphometric appearance. In conclusion, ionizing radiation reduces in vivo intestinal fluid absorption without significant changes in histologic or morphometric appearance. Treatment with vitamin E, but not misoprostol, protects gastrointestinal mucosa against radiation-induced absorptive injury. PMID- 1735338 TI - Analysis of clinical course of postoperative recurrence in Crohn's disease of distal ileum. AB - In the present study we have investigated whether in patients with Crohn's Disease the clinical course remains the same from the initial disease to postoperative recurrent disease. Fifty-eight resected patients who developed a postoperative recurrence were followed for 4.2 +/- 3 years (median 3 years). The yearly frequency of flare-up was 1.9 +/- 1.0 (median 1.5) in the initial disease and 1.7 +/- 1.0 (median 1.7) in recurrent disease. In patients who experienced complications during the initial disease, the frequency of complications during the course of recurrent disease was significantly higher than in the others (27/42 vs 3/16, P = 0.002). The frequency of obstruction and extraintestinal manifestations in the recurrent disease was higher in patients who suffered these complications in the initial disease than in those who did not (19/29 vs 6/29, P = 0.0006, and 4/5 vs 4/53, P = 0.0008). The cumulative probability of complication during the course of recurrent disease was higher in patients with complications during the initial disease (P less than 0.001). The survival analysis showed that the cumulative probability of obstruction and extraintestinal complication in recurrent disease was higher in patients who suffered these complications in the initial disease (P less than 0.005). These data indicate that the clinical course of Crohn's disease of the distal ileum remains the same from the initial disease to postoperative recurrent disease. This study also suggests that the short-term course of recurrent disease can reasonably be predicted. PMID- 1735339 TI - Evaluation of hepatic density change by dynamic CT in healthy humans and in patients with chronic liver diseases. AB - Dynamic computed tomography using 0.4 ml/kg of 65% meglumine diatrizoate was performed to estimate pharmacokinetics of contrast media in the liver in healthy controls (N = 11), in patients with chronic viral hepatitis (N = 17), posthepatic liver cirrhosis (N = 21), and alcoholic liver cirrhosis (N = 23). The time of peak enhancement (the time interval between peak aortic and liver enhancement) was significantly different between each group. Alcoholic liver cirrhosis was the most prolonged, followed by posthepatic liver cirrhosis, chronic viral hepatitis, and finally controls. A peak enhancement time of 28 sec had a diagnostic accuracy of 97% for chronic liver diseases. A time greater than 44 sec had a diagnostic accuracy for cirrhosis of 96%. The decay time (the time from peak enhancement of the liver to the curve's center of gravity) was also significantly different between each group. Again, alcoholic liver cirrhosis was the longest, followed by posthepatic liver cirrhosis, chronic viral hepatitis, and then the controls. Dynamic computed tomography has many potential applications in studying intrahepatic physiologic events and may contain diagnostic information for chronic liver diseases. PMID- 1735340 TI - Measurement of bile acid half-life using [75Se]HCAT in health and intestinal diseases. Comparison with [75Se]HCAT abdominal retention methods. AB - The diagnostic values in detecting terminal ileum dysfunction using [75Se]HCAT have been assessed for two different scintigraphic techniques in 58 subjects. The measurement of [75Se]HCAT T1/2 in the enterohepatic circulation by daily gallbladder scintigraphy showed 78% sensitivity, 96% specificity, 96% positive predictive value, and 78% negative predictive value at the optimal cutoff level of 2.0 days; lower--but not significantly different--figures were observed for [75Se]HCAT total abdominal retention four and seven days after isotope administration, at the optimal cutoff levels of 40% and 22%, respectively. [75Se]HCAT T1/2 was then evaluated in 60 patients with various intestinal diseases. Sixty-nine percent (9/13) of patients with diarrhea of obscure origin showed abnormal [75Se]HCAT T1/2. Bile acid malabsorption using [75Se]HCAT can be investigated by the noninvasive measurement of its enterohepatic T1/2 and may play a pathogenetic role in patients with diarrhea of obscure origin. PMID- 1735341 TI - Regulation of surface expression of high-affinity receptors for epidermal growth factor (EGF) in hepatocytes by hormones, differentiating agents, and phorbol ester. AB - Freshly isolated adult rat hepatocytes exhibit a nonhomogeneous population of epidermal growth factor (EGF) receptors with about 10,000 high-affinity binding sites (Kd 20 pM) and about 200,000 low-affinity sites (Kd 600 pM) per cell. With culturing as primary monolayers under conditions where the cells show a marked increase in the sensitivity to the growth-stimulatory effect of EGF, a gradual reduction in the number of EGF receptors and an almost complete loss of high affinity EGF receptors is seen. Insulin, which promotes growth of hepatocytes in concert with EGF, enhances the down-regulation of these high-affinity receptors. The differentiating (and growth-inhibitory) agent n-butyrate counteracts this down-regulation and preserves the high-affinity receptors. This effect of butyrate is synergistic with the glucocorticoid agent dexamethasone. Another differentiating agent, dimethylsulfoxide (DMSO), also counteracts the down regulation of high-affinity EGF receptors. Moreover, the tumor promoter, tetradecanoylphorbol acetate (TPA), down-regulates the EGF receptor. This effect is particularly evident when studying the high-affinity receptors up-regulated by prior treatment with butyrate plus dexamethasone. Taken together these results provide strong support for the notion that an inverse relationship exists between expression of high-affinity EGF binding and responsiveness to growth activation by EGF. PMID- 1735342 TI - Outcome of hepatic amebic abscesses managed with three different therapeutic strategies. AB - Three different approaches to hepatic abscesses due to Entamoeba histolytica were compared in 51 patients. The three modes of therapy utilized were: medical therapy with nitroimidazoles (N = 11 patients), open surgical drainage (N = 9 patients), and percutaneous drainage using ultrasound guidance followed by intralesional nitroimidazole administration (N = 31 patients). The results with each form of therapy were assessed clinically and by abdominal ultrasound. Patients receiving combined US-guided drainage and intralesional chemotherapy experienced a faster and overall better clinical response, which was confirmed also by sonographic follow-up of the hepatic lesions. This better response was associated with faster resolution, fewer relapses, and less residual hepatic scarring than either with medical therapy alone or open surgical drainage combined with medical therapy. PMID- 1735343 TI - Hepatobiliary excretion of bacterial formyl-methionyl peptides in rat. Structure activity studies. AB - The bacterial chemotactic peptide formyl-met-leu-phe and its radioiodinated analog formyl-met-leu-[125I]tyr are rapidly excreted by the liver into bile following portal or systemic venous infusions in rats or after absorption from the gut lumen. To determine the molecular structural requirements for hepatobiliary excretion of formyl-methionyl peptides, structure-activity studies using portal venous infusions of 24 structural analogs of formyl-met-leu-tyr were performed in rats with biliary cannulae. Hepatic extraction of peptides was studied in vivo using external gamma counting after portal infusion. Efficient hepatobiliary excretion was not restricted to bioactive formyl peptides, but showed a broad specificity for different amino-acylated (formyl, acetyl, propionyl, carbobenzoxy) di- and tripeptides and no requirement for methionine in position one or for a free carboxy terminus. However, nonacylated peptides and an acyl-amino acid showed little excretion. Hepatic extraction of peptide was also related to N-acylation. Hepatic extraction and excretion of N-acyl peptides were also related to hydrophobicity. Thus, the presence of an N-acyl group is the key determinant of biliary excretion of inflammatory bacterial f-met peptides in the rat. PMID- 1735344 TI - Sphincter of Oddi dysfunction and unexplained abdominal pain: clinical and manometric study. AB - Unexplained, biliary-type abdominal pain is often attributed to an abnormal pressure profile of the sphincter of Oddi. In spite of this assumption, the true prevalence of this type of motor dysfunction among cholecystectomized patients with unexplained abdominal pain is not known. We studied 64 postcholecystectomy patients who were thought to have sphincter of Oddi dysfunction. Radiologically, other than a dilated common bile duct in some, they had no anatomic derangement of their pancreatobiliary tract to explain their symptoms. They were categorized into three groups on the basis of four objective findings suggesting abnormal biliary emptying mechanism. Basal sphincter of Oddi pressure, frequency of phasic contractions, and proportion of retrograde contractions were determined in all patients. Twenty-six (41%) of the patients demonstrated at least one motor abnormality, 16 (25%) had two, and 10 (16%) had all three abnormal parameters. The pressure profile of the sphincter was normal in 38 or 59% of the patients. Seventy-three percent (73%) of the patients in group I, who had three or four of the objective findings for sphincter of Oddi dysfunction, demonstrated at least one motor abnormality. Sixty percent of this group demonstrated an increased basal sphincter of Oddi pressure. On the other hand, only 19% of the patients in group III, who had none of the objective findings, revealed a motor abnormality. Increased basal sphincter of Oddi pressure was noted in 7% of this group. We conclude that, sphincter of Oddi dysfunction, as diagnosed manometrically, explains the recurrent biliary type abdominal pain in a minority of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735345 TI - Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms. A double-blind placebo-controlled clinical trial with cisapride. AB - Gastric and gallbladder emptying after a standard liquid meal were studied in 65 patients with early satiety, bloating, pain at the right hypochondrium or the epigastrium, nausea, and occasionally vomiting. Fifty normal subjects were studied as a control group. Gastric and gallbladder emptying were evaluated by means of real-time ultrasonography (RUS). Serial RUS scans were made after a 12 hr fast and every 15 min after a standard meal for 2 hr. Patients were considered to have delayed gastric emptying or hypokinetic gallbladder when gastric diameters and gallbladder volume evaluated 45 min after meal were 2 SD above the corresponding mean values of the normal subject group. Fifteen patients (23%) were found with delayed gastric emptying and 20 (30.7%) a reduced gallbladder emptying. None of our patients showed delayed gastric emptying and hypokinetic gallbladder simultaneously. The 20 patients with reduced gallbladder emptying were included in a double-blind randomized, placebo controlled, change-over study with cisapride (10 mg three times a day) for 30 days. Cisapride treatment reversed the gallbladder hypomotility within the normal range while placebo did not change the response to meal. Symptom score improved significantly after cisapride and placebo. It is concluded that in dyspeptic patients with reduced gallbladder response to a meal cisapride may be of help in improving the kinetic abnormality. Dyspeptic symptoms, however, do not seem to be corrected with the described gallbladder motor abnormality. PMID- 1735346 TI - Pancreatic ductal and interstitial pressures in cats with chronic pancreatitis. AB - We investigated the etiology of interstitial hypertension in chronic pancreatitis by examining the relationship between pancreatic ductal and interstitial pressures in cats. The main pancreatic duct was cannulated in the tail of the gland and perfused at 1, 2, or 5 ml/hr, to simulate pancreatic secretion. Intraductal and interstitial pressures were measured in four groups of animals: (1) normal cats; (2) normal cats after acutely narrowing the main duct to 25% of its original diameter; (3) normal cats after encasing the body and tail in a rigid latex capsule; and (4) cats with chronic pancreatitis created by narrowing the main duct five weeks earlier. Duct perfusion increased intraductal pressure in all of the cats, but significantly more in groups 2, 3, and 4 compared to group 1. Pancreatic interstitial pressure was unchanged by duct perfusion in groups 1 and 2, but increased in groups 3 and 4. We concluded that the compliant tissue of the normal pancreas expanded to effectively dissipate the increase in duct pressure associated with duct perfusion. In chronic pancreatitis, the inelastic parenchyma and capsule limited the distensibility of the gland, which resulted in elevated interstitial pressures during duct perfusion. PMID- 1735347 TI - Protective effect of antithrombin III in acute experimental pancreatitis in rats. AB - In the present study we investigated the therapeutic action of antithrombin III (AT III) in taurocholate-induced experimental pancreatitis with high lethality in rats. High-dose AT III treatment greatly improved the survival rate not only when given as pretreatment but also when given 2 hr after induction. No favorable effect on survival rate was observed on administration after 5 hr. Both intravascular and intraperitoneal AT III administration locally restored decreased AT III levels in the peritoneal cavity and increased plasma AT III to supranormal levels. The primary pancreatic insult seemed to be unaffected by the treatment, because neither the rise in plasma lipase nor the development of ascites or the extension of the pancreatic necrosis were diminished. Because heparin pretreatment of the rats was also effective, the mechanism of the beneficial action was probably mediated by inhibition of the proteases of the coagulation cascade, thereby preventing intravascular coagulation in the pancreas and distant organs and subsequent systemic complications. The high efficacy of AT III treatment in this experimental model may stimulate clinical studies evaluating the efficacy of AT III treatment in an early stage of acute pancreatitis. PMID- 1735348 TI - Serum pancreatic enzymes in HIV-seropositive patients. AB - Serum concentrations of trypsin and elastase I were determined in 109 HIV Ab positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase I between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions. PMID- 1735349 TI - Manometric patterns using esophageal body and lower sphincter characteristics. Findings in 1013 patients. AB - In order to determine the actual spectrum of abnormal esophageal motility, manometric patterns in 1013 consecutive tracings were established using a classification method that employs esophageal body and lower esophageal sphincter (LES) characteristics. Peristaltic performance and contraction wave parameters were measured in the esophageal body; basal pressure and relaxation were included for the LES. Nine hundred thirty (92%) of the tracings could be completely classified, and 33 different patterns were observed (915 occurring at a rate greater than 1%). Abnormalities were most common in contraction wave parameters (661 tracings, 65%), and least common in LES relaxation (105 tracings, 10%). Patterns most typical of achalasia and diffuse esophageal spasm were found in 6.4% and 5.0% of tracings, respectively. Statistical analysis of the patterns demonstrated that significant bidirectional predictive associations between categories were restricted to features representing pathology-based motor disorders (ie, achalasia and "scleroderma-esophagus"). This systematic classification method is capable of recognizing and cataloging common findings of motor dysfunction in the esophageal body and LES as well as uncommon patterns representing traditional motility disorders. Our findings provide reference data for clinical esophageal manometry. PMID- 1735350 TI - Randomized, double-blind, placebo-controlled crossover trial of pirenzepine in patients with gastroesophageal reflux. AB - A muscarinic receptor subtype 1 (M1) antagonist, pirenzepine, recently has been shown to be relatively free of the usual anticholinergic side effects on esophageal smooth muscle and thus has been implicated for the treatment of gastroesophageal reflux disease (GERD). However, the effect of pirenzepine on GERD remains to be defined. Thirteen patients who demonstrated GERD in a baseline 24-hr ambulatory intraesophageal pH monitoring study were randomized in a double blind crossover fashion to receive pirenzepine and placebo. An ambulatory 24-hr intraesophageal pH monitor was used to assess reduction in reflux (esophageal pH less than 4.0) with respect to position (upright vs supine), to total number of reflux episodes, and to episodes greater than 5 min. A significant effect for pirenzepine was seen for episodes greater than 5 min (t = 2.61, P = 0.023) and a trend towards significance was seen for total (upright and supine positions combined) percent time of reflux (t = 2.13, P = 0.055). Although not statistically significant, pirenzepine consistently showed greater reduction in all parameters of reflux tested. A greater reduction in percent time of reflux in supine vs upright positions (pirenzepine: 58.9% vs 21.4%; placebo: 43.6% vs 7.3%) may be clinically important in prevention of esophageal injury due to reflux in the recumbent position. Pirenzepine may provide a unique alternative for some GERD patients who may be refractory to other therapies of GERD. PMID- 1735351 TI - Esophageal motor dysfunction years after radiation therapy. AB - Well-known complications of radiation to the esophagus are acute esophagitis and strictures. Although radiologic studies have demonstrated motor abnormalities after radiation treatment, clinical aspects have not been described adequately, nor have manometric evaluations been reported. Clinical presentation of dysphagia long after treatment also has not been reported. We describe herein three patients who presented with dysphagia years after radiation therapy. Radiographic, endoscopic, histologic, and manometric studies supported our conclusion that these patients suffered from radiation-induced esophageal motor dysfunction. This report indicates the need, in the proper setting, to consider radiation-induced motor dysfunction as a cause of dysphagia even decades after radiation treatment. PMID- 1735352 TI - Tissue-type plasminogen activator of colonic mucosa in ulcerative colitis. Evidence of endothelium-derived fibrinolytic activation. AB - Microvascular endothelial alterations are thought to be a crucial step for development of hemorrhagic changes in various pathological states. In this study, we determined the activity and amount of tissue-type plasminogen activator (t-PA) in the biopsy specimens from sigmoid colon of patients with ulcerative colitis to evaluate endothelial alterations and vascular changes of permeability. The results of this investigation revealed that mucosal amount of t-PA in the active stage of ulcerative colitis was two- to threefold higher than in healthy controls, while t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to correlate well to the degree of inflammation of colonic mucosa, and t-PA amount was still increased in the inactive stage. The present study indicates that t-PA determination in colonic biopsy specimens may be useful for the evaluation of clinical activity of ulcerative colitis in terms of the mucosal microvascular endothelial changes. PMID- 1735353 TI - Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature. AB - Squamous cell carcinoma is an uncommon form of cancer of the pancreas, comprising 0.5-3.5% of cases. We report an unusual case that occurred in a very young woman and showed cystic characteristics. Interesting radiographic features included extensive pancreatic calcifications and pancreatic duct communication to the mass. A literature review of this rare form of pancreatic cancer is also provided. PMID- 1735354 TI - Effect of total hepatectomy on coagulation and glucose homeostasis in the pig. AB - It has been suggested recently that patients with fulminant liver failure should be prepared for transplantation by early hepatectomy, yet the acute effects of removal of the liver upon the coagulation profile and certain hormones are not known. This study was conducted on totally hepatectomized pigs that survived up to 27 hr. Measurements were made of serum insulin, plasma glucagon (IRG and GLI), glucose, catecholamines, and the coagulation profile. The increase in serum insulin was directly related to levels of plasma glucose--there was a 100-fold increase in animals with plasma glucose levels greater than 400 mg/100 ml and none when blood glucose was less than 100 mg/100 ml. Plasma glucagon showed a sharp transient increase within 1 hr of hepatectomy and a slow rise thereafter with levels apparently unrelated to serum insulin or plasma glucose. There was a transient increase in plasma adrenaline but a sharp continuous increase in plasma norepinephrine. No changes of note occurred in the coagulation profile--even levels of fibrinogen only declined by 20% in 27 hr. The study has shown that early total hepatectomy is safe as far as changes in coagulation are concerned but changes in serum insulin and especially plasma norepinephrine may be of more significance. PMID- 1735355 TI - Adult "idiopathic" extrahepatic venous thrombosis. Importance of putative "latent" myeloproliferative disorders and comparison with cases with known etiology. AB - The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a "latent" myeloproliferative disorder has been reported in adults with "idiopathic" EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The "idiopathic" group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17-70) with a median follow up of 96 months (19-372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance. PMID- 1735356 TI - Splenic and portal venous obstruction in chronic pancreatitis. A prospective longitudinal study of a medical-surgical series of 266 patients. AB - The aim of this study was a prospective search for splenoportal venous obstruction (SPVO) in a medical-surgical series of 266 patients with chronic pancreatitis who were followed up a mean time of 8.2 years. SPVO was systematically searched for using ultrasonography and then confirmed by angiography or computed tomography. SPVO was found in 35 patients (13.2%) but was symptomatic in only two. Initial obstruction involved the splenic vein in 22 patients, the portal vein in 10, and the superior mesenteric vein in three. Since venous obstruction extended from the splenic to the portal vein in five patients, the prevalence of portal obstruction was 5.6% (15/266). Acute pancreatitis and pseudocysts were the probable cause of SPVO in 91.4% of our cases. Half the cases of splenic venous obstruction were related to pseudocysts of the caudal pancreas. Esophageal varices were found in two patients and gastric varices in four at the time of diagnosis and during follow-up. At the end of follow-up, 12 patients had undergone splenopancreatectomy (N = 11) or splenectomy (N = 1). Only one patient was operated on for massive esophageal variceal bleeding, and another patient died due to intractable colic variceal bleeding. In four of six patients operated on with portal vein obstruction, surgery was difficult due to venous collaterals. Ten patients were not operated on and 13 patients operated on were not treated for SPVO. The mean follow-up after diagnosis of SPVO for these final 23 patients was 28.9 months. None of these patients bled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735357 TI - Esophageal strictures following endoscopic variceal sclerotherapy. Antecedents, clinical profile, and management. AB - We have evaluated 169 patients with portal hypertension receiving endoscopic variceal sclerotherapy in order to assess the predisposing factors, clinical profile, and treatment response of sclerotherapy-induced esophageal strictures. Of the 129 patients included in the final analysis, 20 (15.5%) developed persistent esophageal stricture. No significant difference was found with respect to age, nature of sclerosant (absolute alcohol, ethanolamine oleate, or sodium tetradecyl sulfate), etiology of portal hypertension, Child's class, initial variceal score, or intensity of sclerotherapy schedule between the patients who developed strictures and those who did not. However, female sex (P less than 0.01) and persistent esophageal ulceration (P less than 0.05) did predispose to stricture formation. Sclerotherapy-induced strictures presented with a variable grade of dysphagia, were always solitary, and were localized to the lower end of esophagus. Most of these could be dilated rapidly using Eder-Puestow metal olives (3.15 +/- 0.80 dilatation sessions per patient). Stricture formation did interrupt an effective sclerotherapy program but only temporarily, and successful variceal obliteration could be obtained after stricture dilatation. PMID- 1735358 TI - Familial primary biliary cirrhosis associated with impaired concanavalin A induced lymphocyte transformation in relatives. Two family studies. AB - The familial occurrences of biochemical and immunological abnormalities and histocompatibility antigens were studied in 18 healthy first-degree relatives of patients with primary biliary cirrhosis (PBC) in two families. In each of these two families, there were two members who suffered from PBC. All relatives had normal serum aspartate aminotransferase, alkaline phosphatase, bilirubin, total cholesterol, and immunoglobulins except the two, who had a mild elevation of alkaline phosphatase without cholestasis. Autoantibodies were present in some relatives; five (28%) for antithyroglobulin antibody and antithyroid microsomal antibody, one (6%) for antimitochondrial and antinuclear antibody, and one (6%) for rheumatoid factor. Abnormalities of T or B lymphocytes in peripheral blood were detected in two (11%) relatives. Impairment of concanavalin A-induced lymphocyte transformation determined by ethidium bromide fluoroassay was found in seven (39%) relatives, although an abnormal response for phytohemagglutinin was detected in none of the relatives. The HLA haplotypes were not necessarily associated with positive autoantibodies or impaired concanavalin A-induced lymphocyte transformation in these families. These findings suggest that impairment of concanavalin A-inducible lymphocytes (mainly suppressor T cells) is one of the contributing factors in the development of PBC. PMID- 1735359 TI - Intrafamilial variation in hereditary hemochromatosis. AB - A review of 57 families with hereditary hemochromatosis revealed three pairs of HLA-identical, sex-matched siblings in which the younger sibling demonstrated considerably more iron loading than the older sibling. Liver biopsy, chemical hepatic iron determination, iron absorption studies, and number of venesections required were used to support these observations. Nineteen pairs of HLA identical, sex-matched siblings homozygous for hemochromatosis were found in which the iron loading was more marked in the older sibling. There was no evidence of blood loss, difference in alcohol consumption, or dietary iron loading to explain the increased iron loading in the younger sibling. These three families demonstrate that the rate of iron accumulation may vary within a family and that the extent of iron loading in hereditary hemochromatosis is not solely dependent on the duration of iron accumulation. PMID- 1735360 TI - Changes in plasma and duodenal cholecystokinin concentrations after pancreatic duct occlusion in rats. AB - The changes in plasma and duodenal cholecystokinin (CCK) concentrations after pancreatic duct occlusion were examined in rats. The rats were sacrificed 1, 3, 7, 10, 14, and 30 days after occlusion of the duct. Histological examination showed acute inflammation on days 1 and 3 after duct occlusion, interstitial fibrosis and regenerative changes on days 7, 10, and 14, and pancreatic atrophy on day 30. The plasma CCK concentration increased from 0.45 pM to 2.0 pM after the occlusion and then remained high throughout the observation period. In contrast to the stable increase in plasma CCK concentration, the CCK content in the duodenum increased on days 1 and 3, decreased on day 7, increased on day 10, reaching over the control level on day 14, and then returned to the control level on day 30. Administration of boiled and 10-fold concentrated rat pancreatic juice or human pancreatic secretory trypsin inhibitor for seven days after pancreatic duct occlusion reversed the decrease in duodenal CCK content. The major molecular forms of duodenal CCK were CCK-8, -33, and -58. These results indicate that (1) basal plasma CCK concentration did not reflect the duodenal CCK content, (2) duodenal CCK content was well correlated with a decrease in inflammation in the pancreas, and (3) a nonenzymatic component in the pancreatic juice reversed the decrease in duodenal CCK content and body weight caused by pancreatic duct occlusion. PMID- 1735361 TI - Helicobacter pylori and luminal gastric pH. Relationships in nonulcer dyspepsia. AB - The relationships between gastric pH and Helicobacter pylori infection were studied in 37 consecutive subjects affected with nonulcer dyspepsia. Each underwent esophagogastroduodenoscopy with multiple gastric biopsies for both H. pylori and histologic assessment, and 24-hr antral pH monitoring. H. pylori was harbored by 59.5% of the subjects with whole gastric spread of infection in all but one patient. Histologic gastritis was shown in 70.3% of the subjects. H. pylori was strongly associated with gastritis, both antral nonatrophic and multifocal atrophic. The ranges of 24-hr pH values were 1.3-6.9 in the H. pylori positive and 1.2-6.8 in the H. pylori-negative group. Differences in pH values between the two groups were not significant. Moreover, the mean percent time duration of pH above 2, 4, and 6 did not significantly differ between the two groups. Therefore, this study has shown that chronic H. pylori infection is not related to luminal gastric pH. PMID- 1735362 TI - Nonsteroidal antiinflammatory drugs and mortality from peptic ulceration in West Germany: 1952-1989. AB - Previous epidemiological studies have examined peptic ulcer mortality in West Germany until 1980 and reported decreasing mortality rates for young and middle aged people and increasing mortality rates for elderly people. Data on ulcer mortality until 1989 show that these trends have continued. The rise in mortality rates in the oldest age groups could be explained partially by their greater life expectancy, thus increasing the risk of lethal ulcer complications. Analysis of NSAID consumption in relation to the mortality pattern shows that there is an inverse correlation between NSAID consumption as measured by the number of prescriptions and peptic ulcer mortality. It is concluded that NSAID consumption is not responsible for the mortality pattern of peptic ulcer in West Germany. PMID- 1735363 TI - Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol or N-ethylmaleimide in rats. AB - We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on propranolol- or N ethylmaleimide-sensitive mechanisms. Propranolol was administered in doses (2 and 20 mg/kg) that provided dose-related blockade of beta-adrenoceptors (significant decreases in heart rate). N-Ethylmaleimide was administered in doses that previously had been shown to increase gastric vascular permeability (10 mg/kg) or inhibit gastric mucosal sulfhydryl compounds (50 mg/kg). At 0.5 hr after these or control subcutaneous pretreatments, the rats received intragastric nicotine (4 mg/kg) or vehicle. One hour later 40% ethanol was given intragastrically. The gastric corpus mucosal lesions were recorded by polaroid photographs after another hour, and their areas measured unbiasedly by computerized image analysis. The results showed that N-ethylmaleimide, but not propranolol, aggravated ethanol induced gastric mucosal injury. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of propranolol- or N-ethylmaleimide-sensitive mechanisms. PMID- 1735364 TI - Role of endogenous secretin and cholecystokinin in intraduodenal oleic acid induced inhibition of gastric acid secretion in rats. AB - We investigated a possible role of endogenous secretin and cholecystokinin (CCK) in inhibition of gastric acid secretion induced by intraduodenal administration of oleic acid in rats. Intraduodenal administration of oleic acid emulsion in a dose of 1 mmol/hr resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 micrograms/kg/hr), and this was accompanied by an increase in the plasma concentration of both secretin and CCK, from 1.2 +/- 0.08 pM and 20.6 +/- 1.2 pM to 4.3 +/- 0.18 pM and 31.6 +/- 0.9 pM, respectively (P less than 0.001). Intravenous infusion of secretin (0.05 CU/kg/hr) inhibited pentagastrin-stimulated gastric acid secretion, but CCK-8 (0.03 micrograms/kg/hr) failed, although intravenous infusion of secretin and CCK in those doses produced plasma levels comparable to the levels achieved in response to oleic acid administration. Furthermore, the oleic acid-induced suppression of gastric acid secretion was blocked significantly by intravenous injection of rabbit anti-secretin serum (0.1 ml), but not by intravenous infusion of a CCK-receptor antagonist, CR 1409 (5 mg/kg/hr). Thus, the results of this study indicate that endogenous secretin rather than CCK is involved in the hormonal mechanism regulating the inhibition of gastric acid secretion by intestinal fat in rats. PMID- 1735365 TI - Neurotensin prevents intestinal mucosal hypoplasia in rats fed an elemental diet. AB - Liquid elemental diets are associated with mucosal hypoplasia of both the small intestine and colon. Neurotensin, a tridecapeptide widely distributed in the gut, is trophic for the small intestine of rats fed a normal chow diet. The purpose of this study was to determine whether neurotensin could reverse the hypoplasia of intestinal mucosa that is associated with feeding a liquid elemental diet. Forty male Sprague-Dawley rats were randomized into five groups. Four groups were fed (for seven days) a glutamine-free liquid elemental diet. Subcutaneous injection of saline (control) or neurotensin (33, 100 or 300 micrograms/kg) were given to the groups of rats every 8 hr for seven days. Group five (Chow) received rat chow ad libitum for seven days. Rats were killed on day 8, and the proximal jejunum, distal ileum, and proximal colon removed. Mucosal weight, DNA, RNA, and protein contents were determined. Neurotensin (300 micrograms/kg) increased the cellularity of the small intestinal mucosa and reversed mucosal hypoplasia due to an elemental diet; a more pronounced effect was noted in the jejunum compared to the ileum. Neurotensin (33 and 100 micrograms/kg) increased mucosal DNA content in the jejunum but was not effective in reversing the hypoplasia. Neurotensin had no effect on growth of colonic mucosa. These results suggest that neurotensin may be an important trophic hormone for the small intestine. Administration of neurotensin may alleviate hypoplasia of the small bowel mucosa and maintain functional integrity of the gut during prolonged feeding of an elemental diet. PMID- 1735366 TI - PAF-acether and acetylhydrolase in stool of patients with Crohn's disease. AB - PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments. PMID- 1735367 TI - Reinnervation of villi of rat jejunum following severe mucosal damage. AB - We studied the time course of the regeneration of the jejunal mucosa of the rat after it was damaged by exposure to the surfactant, benzalkonium chloride. We placed particular emphasis on assessing the morphology of the nerve fibers within the villi during and after regeneration. The application of benzalkonium chloride resulted in virtually complete loss of villi within the treated segment; however, the crypts were only partially damaged. The mucosa began to regenerate within 6 hr of the insult. The villus lengths and crypt depths returned to pretreatment values within two to four days. The mucosal innervation was assessed through immunohistochemistry for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and neuron-specific enolase (NSE). At all stages of regeneration, VIP, NPY, and NSE immunopositive fibers within the lamina propria extended to the tips of the villi. The density of the immunopositive fibers in the lamina propria at four days after mucosal insult was similar to that in control tissues regardless of the neuronal marker visualized. We conclude that the nerve fibers innervating the small intestinal mucosa grow at a rate of approximately 100 microns/day and that the entire length of each villus contains nerve fibers throughout the regeneration process. The innervation of the regenerated mucosa appears identical to that of control mucosa. PMID- 1735368 TI - Duodenal varices. A neglected cause of massive, recurrent gastrointestinal bleeding. AB - Bleeding from duodenal varices in portal hypertension may not be recognized, resulting in a delay in diagnosis. Early detection is important as duodenal varices are a potential source of massive hemorrhage. We report two cases with recurrent upper gastrointestinal hemorrhage in whom accurate diagnosis was made only after extensive investigation including repeated endoscopic examination. PMID- 1735369 TI - Acute upper gastrointestinal hemorrhage caused by gallstone impaction in the duodenal bulb. AB - An unusual case of upper gastrointestinal hemorrhage caused by gallstone impaction in the duodenal bulb (Bouveret's syndrome) is reported. Endoscopy was used to make the diagnosis rapidly and surgery was performed to provide definitive treatment. Bouveret's syndrome must be kept in mind as a rare cause of upper gastrointestinal hemorrhage. PMID- 1735370 TI - Chronic intestinal pseudoobstruction with myopathy and ophthalmoplegia. A muscular biochemical study of a mitochondrial disorder. AB - The association of chronic intestinal pseudoobstruction with ophthalmoplegia has been reported previously in visceral myopathies. We report a case of this association in which muscle mitochondria had a crystalline appearance, a dense core, and decreased cytochrome c oxidase and succinate cytochrome c reductase activities. The absence of evident mitochondrial DNA deletion in the skeletal muscle of this patient does not exclude the possibility of localized deletion or mutation of mitochondrial DNA in digestive muscle. PMID- 1735371 TI - Familial visceral myopathy. A family with involvement of four generations. AB - A family with the autosomal dominant form of familial visceral myopathy is described involving four generations. The members illustrate several different clinical presentations including severe constipation, diarrhea, alternating constipation and diarrhea, volvulus, urinary tract infection, and retention of urine. One patient's history suggested that the uterus may have been involved. Diagnosis of this rare disease requires an awareness of the variable presentation and a careful histological examination of full-thickness sections of bowel. The potential pitfalls in both histological and clinical diagnosis of this condition are demonstrated in this family's history. The extensive involvement of small and large bowel in at least two family members is unusual in the autosomal dominant form of the disease, but their course has so far been favorable, lending further evidence to the impression that prognosis is good. This is of importance for genetic counseling of families who have this very rare disease. PMID- 1735372 TI - Villous adenomatosis of duct of Wirsung revealed by wirsungorragie: evolution and surgical management. AB - A patient presenting with wirsungorragie was found to have a villous adenoma of the duct of Wirsung. The lesion was treated by a left pancreatectomy. Five years later he presented with recurrent wirsungorragie and was found to have a villous adenomatosis of the main pancreatic duct and of its side branches. This time a Whipple procedure was performed, achieving a total pancreatectomy. The patient has remained well for 12 months. This case of villous adenomatosis is, to our knowledge, the first one to be revealed by a wirsungorragie. PMID- 1735373 TI - Fulminant hepatic failure in nonmetastatic renal cell carcinoma. AB - Paraneoplastic manifestations including reversible abnormal serum liver biochemistry are known to occur in at least one third of patients with renal cell carcinoma. This hepatic dysfunction has always been regarded as benign in nature and attributed to reactive nonspecific hepatitis. In contrast to this belief, we report here a more devastating course of an asymptomatic patient with nonmetastatic renal cell carcinoma which ranged from mere serum liver biochemistry derangement to a fatal end with fulminant hepatic failure within 10 days. To our knowledge, this is the first report of such a case. PMID- 1735374 TI - [The endoscopic treatment of malignant biliary tract stenoses with endoprostheses]. AB - In 65 patients (36 men, 29 women; mean age 74 [43-90] years) obstructive jaundice caused by malignant biliary stenosis was treated by endoscopic retrograde insertion of a 10 or 12 F synthetic endoprosthesis. The rate of complications of the endoscopic intervention was 5% (n = 3), 30-day mortality rate was 11% (n = 7) and method-related mortality was 8% (n = 5). Good drainage was achieved in 39 of 41 patients (95%) with the 12 F endoprosthesis, and in 15 of 21 patients with a 10 F one (71%) (P less than 0.001). Renewed jaundice due to prosthesis occlusion occurred in 31 patients an average of 103 (11-350) days after placement. Interval until occlusion correlated with the site of the stenosis and the length of the endoprosthesis. Jaundice recurred earlier in patients with long prostheses and proximal biliary stenosis than in those with a short prosthesis and distal stenosis. In 20 patients with renewed jaundice the endoprosthesis was replaced endoscopically. At that time 13 of the patients had a cholangitis. Occlusion of the new endoprosthesis was more common in patients with cholangitis (9 of 13) than those without (2 of 7; P less than 0.05). These findings indicate that endoscopic biliary tract drainage should be performed with as short a 12 F endoprosthesis as possible. In view of the potential need for early change of endoprosthesis the biochemical parameters of cholestasis should be regularly monitored. PMID- 1735375 TI - [Transient complete AV block as a sequela of Borrelia myocarditis]. AB - A 49-year-old man suddenly developed dyspnoea, sweating, fever (up to 38.5 degrees C), vertigo and angina. After emergency admittance to hospital the ECG showed 3 degrees A-V block, requiring temporary pacemaker insertion. The patient reported that a month before he had been bitten, probably by a tick. Serological tests demonstrated a recent Borrelia infection (rise of IgG antibody titre to 1:2048, IgM antibody titre to 1:128). Coronary angiography excluded any haemodynamically significant coronary heart disease as a cause of the conduction disorder. Myocardial biopsy showed changes pointing to a past myocarditis. This suggested Borrelia infection as the cause of the complete A-V block. Under treatment with broad-spectrum antibiotics for 15 days the fever subsided and the ECG became normal. Shortly before discharge, an elevated pulmonary wedge pressure on 150 W exercise indicated persistence of mild left-ventricular failure. PMID- 1735376 TI - [The therapy of advanced breast carcinoma in men]. AB - Four men (mean age 50 [42-57] years) were treated for advanced carcinoma of the breast, two of them by chemotherapy alone. Survival time in the latter two after start of the chemotherapy was 5 and 8 months, respectively. The third patient received both hormone and chemotherapy from the start because of unfavourable prognostic criteria. For 15 months the tumour stage remained unchanged until the patient developed incomplete paraplegia which improved greatly after decompression laminectomy. This has been followed for four months by renewed hormonal and chemotherapy. The fourth patient received tamoxifen for seven months, with intrapleural administration of cytostatic agents and finally pleurectomy for recurrent malignant pleural effusions. For 4 months he has again been receiving hormonal and chemotherapy. These cases illustrate that if there are unfavourable prognostic criteria chemotherapy should be added to conventional hormone therapy. PMID- 1735377 TI - [The therapy of corrosive esophageal burns]. PMID- 1735378 TI - [Acute respiratory infections by Chlamydia pneumoniae]. PMID- 1735379 TI - [The consideration of physicians in practice in the classification of senior physicians according to the Federal Employees Collective Wage Agreement. The judgement of the Wupperthal Labor Court of 24 January 1990]. PMID- 1735380 TI - [The antiphospholipid syndrome]. PMID- 1735381 TI - [Antirheumatics and anticoagulants]. PMID- 1735382 TI - [Primary sclerosing cholangitis]. PMID- 1735383 TI - [Hyperprolactinemia in malignant lymphomas]. PMID- 1735384 TI - [Chorion villi biopsy: a boon or risky alternative in prenatal diagnosis?]. PMID- 1735385 TI - [The chemical composition of gallstones and their suitability for litholysis and lithotripsy]. AB - The chemical composition of gallstones removed at surgery from 107 patients (81 women, 26 men; mean age 59 [18-85] years) was examined. In 64 women (79%) and 21 men (81%) microchemical analysis demonstrated concrements with a more than 50% cholesterol content (500 mg/g). Using as definition of cholesterol stones a 75% cholesterol content, only 35 women (43%) and 10 men (39%) would be classified as cholesterol stone carriers. Grossly visible layer formation was present in 18 stones; in eight stones calcium content was higher in the outer layer than in the core. There was no demonstrable relationship between gallstone composition and age. PMID- 1735386 TI - [The coincidence of rapidly progressing dilated cardiomyopathy and primary hyperparathyroidism. The course before and after the removal of a parathyroid adenoma]. AB - Severe cardiac arrhythmias (Lown class IVa), rapid loss of physical capacity and dyspnoea on the slightest exertion occurred in a 55-year-old man with idiopathic dilated cardiomyopathy. In the preceding year he had recurrent diarrhoea and lost 23 kg in weight. He was found to have hypercalcaemia (3-3.2 mmol/l). The heart failure significantly improved under treatment with twice daily 12.5 mg captopril, 100 mg spironolactone daily, furosemide 40 mg twice daily, and digitoxin 0.07 mg daily. The arrhythmia responded to verapamil 80 mg and quinidine 160 mg, both drugs three times daily. Primary hyperparathyroidism was found to be the cause of the hypercalcaemia (parathormone 84 pmol/l). After the parathyroid adenoma had been removed the patient's condition again improved markedly. There were only rare monotopic extrasystoles, cardiac size regressed, and diuretics were no longer necessary. His medication at present is verapamil (80 mg three times daily), captopril (12.5 mg three times daily) and digitoxin (0.07 mg daily). It is concluded that the hypercalcaemia influenced the severity of the cardiomyopathy. It would seem that both intra- and extracellular calcium homoeostasis is of great importance in dilated cardiomyopathy. PMID- 1735387 TI - [Hemangiosarcoma of the liver. The diagnostic difficulties and therapeutic possibilities]. AB - A 65-year-old man complained of decreasing physical capacity and weakness over the preceding six months, associated with marked painless jaundice and subsequently ascites. Despite extensive tests, some invasive, in three different hospitals no cause was found of the patient's symptoms and the marked though nonspecific abnormalities of various biochemical values (raised bilirubin concentration; increased alkaline phosphatase activity). Liver transplantation was performed because of progressive liver failure, without a firm diagnosis being established. At operation the liver was found to contain a haemangiosarcoma. The patient died 14 months after the transplantation of a suppurative cholangitis. At autopsy neither metastases nor recurrences were found. PMID- 1735388 TI - [The modern diagnosis of malignant melanoma]. PMID- 1735389 TI - [Premedication before endoscopies]. PMID- 1735390 TI - [The prescription of substitute drugs for the drug-dependent]. PMID- 1735391 TI - [Fish poisoning: the causal role of histamine]. PMID- 1735392 TI - Environmental Mutagen Society, 23rd annual scientific meeting. Reno, Nevada, March 15-19, 1992. Abstracts. PMID- 1735393 TI - Acid-base status following glycine absorption in transurethral surgery. AB - Forty patients were studied at precisely timed 10 min intervals during transurethral prostatic resection under epidural analgesia. Blood gases, serum sodium, and volumetric irrigating-fluid balance were measured. A decrease in the serum sodium level of less than 5 mmol litre-1 was recorded in 28 patients (the 'normal TUR' group). In 12 patients, the decrease was 5 mmol litre-1 or more, which corresponded to an average absorption of irrigant of 1 litre of 2.2% glycine solution (range 0.6-2.9; the 'absorption' group). Mild metabolic acidosis often developed during the operations, but this was of similar degree in the two groups. It was concluded that uptake of irrigating fluid containing glycine does not alter the acid-base status so long as the TUR syndrome does not develop. PMID- 1735394 TI - General anaesthesia versus epidural anaesthesia for primary caesarean section--a comparative study. AB - Forty-seven healthy parturients undergoing elective Caesarean section were randomly allocated to either general anaesthesia (n = 24) or epidural anaesthesia (n = 23) under standardized anaesthetic and surgical conditions. Seven women of the epidural group required additional systemic analgesia or sedation following delivery of the neonate. Nine of 24 newborns obtained 1-min Apgar scores below 7 after general anaesthesia compared to only 3/23 after epidural anaesthesia. The time period to establish normal colour in the babies was 2.2 min after epidural and 4.9 min after general anaesthesia. Three of the 24 general-anaesthesia newborns demonstrated a tendency to hypotonia compared to only one in the epidural group. Twenty-four hours and 7 days after delivery all infants of both groups were completely normal. At the time of delivery maternal PO2 was higher in the general anaesthesia compared to the epidural group, due to higher inspired oxygen concentrations. Comparable results were obtained in umbilical PO2 venous values; lower pH values, however, were observed in the umbilical artery after general anaesthesia. There were no significant differences in the glucose levels between the groups. A significant correlation was established between uterine incision-delivery interval and 1-min neonatal Apgar scores in the general anaesthesia group, but not in the epidural group. Our investigation did not show either the incision-delivery interval or the start of operation-delivery interval to play a role in neonatal outcome. Epidural anaesthesia is superior to general anaesthesia in Caesarean section under normal conditions with regard to neonatal outcome. Whether this is also true for critical conditions cannot be concluded from this study. PMID- 1735395 TI - Intravenous tramadol for post-operative pain--comparison of intermittent dose regimens with and without maintenance infusion. AB - Thirty-five ASA Grade I-II females received tramadol 150 mg intravenously followed randomly and double-blind by an infusion of either tramadol 15 mg h-1 (Group I) or saline (Group II) and tramadol 100 mg bolus on demand for the treatment of post-operative pain. Patients in Group I required 60% less tramadol on demand (P less than 0.01) and had better pain relief after operation (P less than 0.05) than those in the group given saline. Total tramadol consumption, however, was about 30% higher in Group I (P less than 0.05) and was associated with an increased incidence of minor side-effects. In both groups median serum tramadol concentrations peaked at 15 and 60 min and decreased after the second peak steadily (P less than 0.001). Tramadol failed to relieve pain within 2 h after the beginning of treatment in 6% (Group I) and 20% (Group II) of the patients. It is suggested that use of an i.v. maintenance tramadol infusion in addition to on-demand i.v. tramadol boluses is a safe and recommended mode of post-operative intravenous pain therapy. PMID- 1735396 TI - Comparison of intravenous diclofenac, indomethacin and oxycodone as post operative analgesics in patients undergoing knee surgery. AB - The non-steroidal anti-inflammatory drugs diclofenac, indomethacin and oxycodone were compared in the treatment of pain after arthroscopy or arthrotomy of the knee in a double-blind, randomized trial. A single and, if needed, a repeated dose of one of the following six dose and drug alternatives was given intravenously for post-operative pain relief: diclofenac 37.5 mg or 75 mg, indomethacin 25 mg or 50 mg and oxycodone 5 mg or 10 mg. Oxycodone 5 mg i.v. was used as a rescue medication whenever the patient needed further pain relief after the two doses of the trial drugs. The observation period was 14 h. In the diclofenac group the patients needed significantly less trial and rescue analgesics than in the indomethacin (P less than 0.001) and oxycodone (P less than 0.05) groups, the latter groups being equal in this respect. Both the duration from the first trial drug infusion to the second trial medication and to the first rescue medication were significantly longer in the diclofenac group than in the indomethacin group (P less than 0.05 and less than 0.01, respectively). PMID- 1735397 TI - Effect of chronic nifedipine therapy on the haemodynamic response to phenylephrine before and during halothane anaesthesia. AB - We evaluated the effect of chronic oral nifedipine therapy (30-80 mg day-1) on the haemodynamic response to the alpha 1-agonist phenylephrine (PE) in 10 patients before and during halothane anaesthesia. The response was compared to a control group of eight patients not taking any cardiovascular drugs. No patients had ganglionic, beta-adrenergic, or muscarinic pharmacological blockade as in prior studies in the literature, and thus had intact cardiovascular reflexes. In all patients, PE caused a dose-related increase in arterial pressure and fall in heart rate and cardiac index. The response in patients taking nifedipine was not significantly different from that measured in controls. One-per-cent halothane in oxygen did not alter the overall haemodynamic response to PE in either group. PMID- 1735398 TI - Interaction between thiopentone and subhypnotic doses of ketamine. AB - The hypnotic effects of thiopentone and ketamine were studied in ASA Grade I female patients aged 20-30 without premedication. The dose-response curves of ketamine 0.4 mg kg-1 and thiopentone following ketamine 0.4 mg kg-1 were determined by probit analysis. The interaction between ketamine and thiopentone was found to be an antagonistic one. This effect can be interpreted as a consequence of the different neurophysiological spectra of action of the two drugs. PMID- 1735399 TI - Sympathetic blockade by thoracic epidural anaesthesia suppresses renin release in response to hypotension, but activates the vasopressin system. AB - To determine whether or not the blockade of sympathetic efferents by epidural anaesthesia blunts the normal increase in plasma renin activity in response to hypotension, we assessed the effect of hypotensive thoracic epidural anaesthesia with widespread sympathetic blockade on plasma renin activity. Plasma renin activity and vasopressin concentration, arterial pressure, and serum osmolality were measured in 17 patients before and after random epidural injection of either 6.7 ml of 0.75% bupivacaine (n = 7) or the same volume of saline (n = 10). As an indicator for efferent sympathetic drive, skin temperatures were measured on the hand and foot. A decrease in mean arterial pressure by more than 25% of baseline values was prospectively defined as hypotension requiring intervention. Thoracic epidural anaesthesia induced a decrease in mean arterial pressure of 24 mmHg (range 16-47) from 101 mmHg to 77 mmHg (P less than 0.001 vs. saline). Despite hypotension, plasma renin activity remained unchanged [medians 2.9 ng ml-1 h-1 (0 9.1) vs. 3.4 ng ml-1 h-1 (0-13.8)]. In contrast, vasopressin concentrations increased from a median of 3.8 pg ml-1 (0.5-8.2) to 6.0 pg ml-1 (4.2-33.6; P = 0.025). Both hand and foot skin temperatures increased significantly indicating widespread extent of sympathetic blockade. Serum osmolality did not change. With epidural saline, variables remained unchanged. Thus, during hypotension induced by widespread attenuation of efferent sympathetic drive through thoracic epidural anaesthesia, renin activity did not change, whilst vasopressin concentrations increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735400 TI - A prospective evaluation of the failure rate of spinal anaesthesia for transurethral prostatic resection. AB - The rate of failed spinal anaesthesia, defined as the need for unplanned general anaesthesia, was evaluated in a prospective study involving 137 patients undergoing transurethral resection of the prostate (TURP). The incidence of sensations at the operative site which did not require general anaesthesia was also evaluated. Attention to details was emphasized in the technique. Patients randomly received either hyperbaric Niphanoid tetracaine (n = 74; 6 or 10 mg) or hyperbaric bupivacaine (n = 61; 6 mg), with or without adrenaline. General anaesthesia was necessary in one patient (0.72%). Twelve additional patients reported sensations at the operative site which were rapidly relieved by light intravenous supplementation with low doses of fentanyl and/or thiopentone. The patients reporting sensations did not differ in demographic characteristics, spinal technique, local anaesthetic, or degree of sensory or motor blockade. Addition of adrenaline to the 6-mg doses of both tetracaine and bupivacaine decreased the incidence of sensations at the operative site. PMID- 1735401 TI - Tympanometry for middle-ear effusion in unconscious ICU patients. AB - Eighty-six bilateral impedance audiometries were performed weekly in 35 unconscious ICU patients. Tympanometry showed the presence of middle-ear effusion in 43.3% of the examinations (80% of the patients). The incidence of effusion was significantly higher in patients older than 50 years, in intubated and mechanically ventilated patients and in the presence of microbial colonization of the upper airways. The acoustic reflex (AR) was characterized by increased threshold values in 23.8% of the examinations and was absent in 41.3%. Abnormal or absent ARs were usually associated with middle-ear effusion or tube malfunction. PMID- 1735402 TI - The additional work of breathing through Portex Polar 'Blue-Line' pre-formed paediatric tracheal tubes. AB - The work of breathing through north- and south-facing Portex Polar 'Blue-Line' paediatric tracheal tubes of sizes 3.0-7.0 mm ID has been measured using sinusoidal flow at equivalent ventilatory rates of 10-50 breaths min-1 with tidal volumes of 10-500 ml. North-facing tubes are designed to sit with the connection on the forehead after intubation, whilst south-facing ones are designed so that the connection sits on the chin of the patient. It was found that the total work of breathing through north-facing tubes is approximately 8% higher than the total work of breathing through south-facing tubes of the same size, irrespective of tidal volume or respiration rate. The total work of breathing was dependent on total tube length but independent of tube design. The endotracheal connectors themselves were found to contribute a significant proportion of the total work of breathing but there was no significant difference between the inspiratory and expiratory performance of the tubes. PMID- 1735403 TI - Influence of the pulmonary circulation on adrenaline pharmacokinetics during cardiopulmonary resuscitation. AB - The influence of the pulmonary circulation on the pharmacokinetics and -dynamics of endogenously released, and intravenously injected (10 micrograms kg-1), and endobronchially (e.b.) administered (100 micrograms kg-1) adrenaline was investigated in an animal cardiopulmonary-resuscitation (CPR) model. During resuscitation 80% of endogenously released and i.v. adrenaline was eliminated before reaching the arterial circulation, whereas arterial availability of adrenaline was higher than mixed-venous availability in the e.b.-medicated animals. Success of resuscitation seemed to depend on maximum adrenaline concentrations and drug availability in arterial blood. Although the average amount of endogenously released adrenaline was calculated to be equivalent to an i.v. bolus of 8 micrograms kg-1, additional i.v. or e.b. adrenaline medication resulted in higher arterial plasma concentrations, improved circulation during CPR, and better resuscitability. It is concluded that, even without a specific pulmonary metabolism, a drastic decrease in blood flow can lead to significant arterio-venous gradients in plasma concentrations and availability of a drug with a very high clearance like adrenaline. PMID- 1735404 TI - Physiological changes and gastro-intestinal symptoms as a result of ultra endurance running. AB - One hundred and seventy-two competitors of the Swiss Alpine Marathon, Davos, Switzerland, 1988, volunteered for this research project. Of these volunteers 170 (158 men, 12 women) finished the race (99%). The race length was 67 km with an altitude difference of 1,900 m between the highest and lowest points. Mean age was 39 (SEM 0.8) years. Average finishing times were 8 h 18 min (men) and 8 h 56 min (women). Loss of body mass averaged 3.4% body mass [mean 3.3 (SEM 0.2)%; 4.0 (SEM 0.4)%; men and women, respectively]. Blood samples from a subgroup of 89 subjects (6 women and 83 men) were taken prior to and immediately after completion of the race. Changes in haemoglobin (9.3 mmol.l-1 pre-race, 9.7 mmol.l 1 post-race) and packed cell volume (0.44 pre, 0.48 post-race) were in line with the moderate level of dehydration displayed by changes in body mass. Mean plasma volume decreased by 8.3%. No significant changes in plasma osmolality, sodium, or chloride were observed but plasma potassium did increase by 5% (4.2 mmol.l-1 pre race, 4.4 mmol.l-1 post-race). Mean fluid consumption was 3290 (SEM 103) ml. Forty-three percent of all subjects, and 33% of those who gave blood samples, complained of gastro-intestinal (GI) distress during the race. No direct relationship was found between the quantity or quality of beverage consumed and the prevalence of GI symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735405 TI - Seasonal changes in performance and free testosterone: cortisol ratio of elite female rowers. AB - The aim of this study was to investigate the seasonal behaviour of the plasma free testosterone: cortisol ratio (FTCR) and to relate hormonal changes to daily training volume and performance parameters on a rowing ergometer in elite female rowers. During 9 months of training preceding the 1988 Olympic Games the resting values of the FTCR in six elite female rowers were regularly (ten times) studied. Daily training volume was analysed in terms of rowed distance (lrowed) and time (t). In addition, two performance parameters, the power at 4.0 mmol.l-1 lactate concentration in the blood and the maximal power, were determined by a test on a rowing ergometer. The results indicated that the mean FTCR test value did not differ significantly from the level of the initial test or from the mean value of the directly preceding test. A significant negative correlation (r = -0.98, P less than 0.01) between FTCR and lrowed was found in a period i.e. at a training camp, when there was a sudden increase in training volume. When FTCR was related to t a significant positive correlation (r = 0.88, P less than 0.05) was found only for the period at the training camp. Our data further suggested that the FTCR alone was not an adequate indicator for the anabolic/catabolic balance in elite female rowers. This finding was contrary to previous findings in elite male rowers. However, in training practice the FTCR seems useful as an indicator of the hormonal training status of elite female rowers when complemented with data about total and free testosterone, performance parameters and knowledge concerning cyclic variations of the FTCR. PMID- 1735406 TI - Relationship between plasma potassium and ventilation during successive periods of exercise in men. AB - During and after two successive incremental cycle ergometer tests (tests A and B), plasma potassium concentration ([K+]p), plasma pH (pHp), plasma partial pressure of carbon dioxide, blood lactate concentration ([Lac-]b) and ventilation (VE) were measured. While there was a good correlation between the increase in [K+]p and VE or pHp, respectively, in test A, in test B a close correlation was found only between the increase in VE and [K+]p (r greater than 0.9 for nearly all single cases; r was 0.84 and 0.89 for all (pooled) cases in tests A and B, respectively; the correlation coefficients between changes in pHp and VE in tests A and B were r = 0.74 and r = 0.28, respectively, and r = 0.89 and r = 0.10 between the changes in [Lac-]b and VE in tests A and B). The close relationship for individuals between VE and [K+]p in tests A and B supported the hypothesis that the extracellular increase in [K+] may contribute to the ventilatory drive during exercise. The comparison of the results of tests A and B further indicated that the relationship between pHp and VE was dependent on the experimental design, and that pHp and VE changes are unlikely to be cause and effect. PMID- 1735407 TI - Metabolic, body temperature and hormonal responses to repeated periods of prolonged cycle-ergometer exercise in men. AB - This study was designed to find out whether rest intervals and prevention of dehydration during prolonged exercise inhibit a drift in metabolic rate, body temperature and hormonal response typically occurring during continuous work. For this purpose in ten healthy men the heart rate (fc), rectal temperature (Tre), oxygen uptake (VO2), as well as blood metabolite and some hormone concentrations were measured during 2-h exercise at approximately 50% maximal oxygen uptake split into four equal parts by 30-min rest intervals during which body water losses were replaced. During each 30-min exercise period there was a rapid change in Tre and fc superimposed on which, these values increased progressively in consecutive exercise periods (slow drift). The VO2 showed similar changes but there were no significant differences in the respiratory exchange ratio, pulmonary ventilation, mechanical efficiency and plasma osmolality between successive periods of exercise. Blood glucose, insulin and C-peptide concentrations decreased in consecutive exercise periods, whereas plasma free fatty acid, glycerol, catecholamine, growth hormone and glucagon concentrations increased. Blood lactate concentrations did not show any regular drift and the plasma cortisol concentration decreased during the first two exercise periods and then increased. In conclusion, in spite of the relatively long rest intervals between the periods of prolonged exercise and the prevention of dehydration several physiological and hormonal variables showed a distinct drift with time. It is suggested that the slow drift in metabolic rate could have been attributable in the main to the increased concentrations of heat liberating hormones. PMID- 1735408 TI - Glycogen depletion and resynthesis in the rat after downhill running. AB - To study the effect of downhill running on glycogen metabolism, 94 rats were exercised by running for 3 h on the level or down an 18 degrees incline. Muscle and liver glycogen concentrations were measured before exercise and 0, 48 and 52 h postexercise. Rats were not fed during the first 48 h of recovery but ingested a glucose solution 48 h postexercise. Downhill running depleted glycogen in the soleus muscle and liver significantly more than level running (P less than 0.01). The amount of glycogen resynthesized in the soleus muscle and liver in fasting or nonfasting rats was not altered significantly by downhill running (P greater than 0.05). On every day of recovery the rats were injected with dexamethasone, which induced similar increases in glycogen concentration in the soleus muscle and liver after the 52nd h of the postexercise period in the case of downhill and level running. The glycogen depletion and repletion results indicated that, under our experimental conditions, downhill running in the rat, a known model of eccentric exercise, affected muscle glycogen metabolism differently from eccentric cycling in humans. PMID- 1735409 TI - Sodium citrate ingestion and its effects on maximal anaerobic exercise of different durations. AB - The effects of an alkalising agent were studied in ten subjects who participated in anaerobic testing on a cycle ergometer to determine the effectiveness of sodium citrate (0.5 g.kg-1 body mass) as an ergogenic aid during exercise of 10 s, 30-s, 120-s and 240-s duration. Blood was collected prior to, after ingestion of sodium citrate (NaHCO3), and postexercise, from a heated (43-46 degrees C) fingertip and analysed immediately postcollection for pH, partial pressure of oxygen and carbon dioxide, base excess and blood bicarbonate. Total work undertaken (kJ) and peak power (W) achieved during the tests was also obtained via a work monitor unit. The results indicated that a dose of 0.5 g.kg-1 body mass sodium citrate had no ergogenic benefit for exercise of either 10-s or 30-s duration. Blood bicarbonate concentrations, however, were significantly increased (P less than 0.05) following ingestion of the citrate during these trials. Exercise periods of 120 s and 240 s were significantly increased (P less than 0.05) above the control and placebo conditions following sodium citrate ingestion. Blood bicarbonate concentrations were again increased above control and placebo conditions and blood lactate concentrations were also increased following the citrate trials. The pH decreased significantly (P less than 0.05) in all trials below the control and placebo conditions. On the basis of the exercise undertaken in this study we would suggest that a dose of 0.5 g.kg-1 body mass of sodium citrate could improve anaerobic exercise performance of 120-s and 240-s duration. PMID- 1735410 TI - Muscle fatigue and efficiency in relation to interval duration of successive contractions. AB - The work output, energy consumption and efficiency during repetitive dynamic contractions were calculated for rat extensor digitorum longus muscle. The muscles performed 40 successive dynamic contractions at 37 degrees C (with occluded bloodflow) with interval durations of either 500, 250 or 167 ms. The muscle-tendon complexes were allowed to shorten at the velocity at which they could exert their highest power output (50 mm.s-1). Work output in the first contraction was the same among the three groups with different interval durations. The reduction in work output during the series of contractions differed among the groups, mainly in the last part of the exercise period. In the group with the longest interval duration, work output steadily decreased over the whole contraction period and at the end was approximately 72% of the output in the first contraction. In contrast, after the 30th contraction, work output decreased at a significantly higher rate of approximately 3% of each contraction in the groups with the intermediate and the shortest interval duration. After the last contraction, work output in these groups was approximately 52% of the work output in the first contraction. These differences in fatigue coincided with differences in the reduction in adenosine 5'-triphosphate and the production of inosine-5'-monophosphate. Total work output was not significantly different among the three groups with different interval durations, indicating that the different reductions in work output in the last contractions only had a minor influence on total work output of all 40 contractions. Also high-energy phosphate consumption and efficiency were not significantly different over these three exercise periods. Thus with the protocol used no interval dependent pattern of efficiency could be detected. PMID- 1735411 TI - Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans. AB - The content of anserine and carnosine in the lateral portion of the quadriceps femoris muscle of 50 healthy, human subjects has been studied. Anserine was undetectable in all muscle samples examined. Muscle carnosine values for the group conformed to a normal distribution with a mean (SD) value of 20.0 (4.7) mmol.kg-1 of dry muscle mass. The concentration of carnosine was significantly higher in the muscle of male subjects (21.3, 4.2 mmol.kg-1 dry mass) than in females of a similar age and training status (17.5, 4.8 mmol.kg-1 dry mass) (P less than 0.005). The test-retest reliability of measures was determined on a subgroup of 17 subjects. No significant difference in mean carnosine concentration was found between the two trials [21.5 (4.0) and 22.0 (5.2) mmol.kg 1 dry muscle mass; P greater than 0.05]. The importance of carnosine as a physicochemical buffer within human muscle was examined by calculating its buffering ability over the physiological pH range. From the range of carnosine concentrations observed (7.2-30.7 mmol.kg-1 dry muscle mass), it was estimated that the dipeptide could buffer between 2.4 and 10.1 mmol H+.kg-1 dry mass over the physiological pH range 7.1-6.5, contributing, on average, approximately 7% to the total muscle buffering. This suggests that in humans, in contrast to many other species, carnosine is of only limited importance in preventing the reduction in pH observed during high intensity exercise. PMID- 1735412 TI - Hypertrophy without increased isometric strength after weight training. AB - Eight men (20-23 years) weight trained 3 days.week-1 for 19 weeks. Training sessions consisted of six sets of a leg press exercise (simultaneous hip and knee extension and ankle plantar flexion) on a weight machine, the last three sets with the heaviest weight that could be used for 7-20 repetitions. In comparison to a control group (n = 6) only the trained group increased (P less than 0.01) weight lifting performance (heaviest weight lifted for one repetition, 29%), and left and right knee extensor cross-sectional area (CAT scanning and computerized planimetry, 11%, P less than 0.05). In contrast, training caused no increase in maximal voluntary isometric knee extension strength, electrically evoked knee extensor peak twitch torque, and knee extensor motor unit activation (interpolated twitch method). These data indicate that a moderate but significant amount of hypertrophy induced by weight training does not necessarily increase performance in an isometric strength task different from the training task but involving the same muscle group. The failure of evoked twitch torque to increase despite hypertrophy may further indicate that moderate hypertrophy in the early stage of strength training may not necessarily cause an increase in intrinsic muscle force generating capacity. PMID- 1735413 TI - Segmental inhibition of laser-evoked brain potentials by ipsi- and contralaterally applied cold pressor pain. AB - An experiment was designed to quantify the inhibitory effect of cold pressor pain (ice water immersion) on brain potentials evoked by acute laser-induced pain. One hand (including the C7 dermatome) was immersed into ice water and simultaneously the laser-evoked brain potentials were elicited consecutively from the right and left lower forearms within the C7 dermatomes. The cold pressor pain was continuously rated on a visual analogue scale (VAS). The size of the averaged brain potentials evoked from the ipsi- and contralateral C7 dermatomes were reduced significantly during cold pressor pain. The largest decrease was obtained for the potentials evoked within the C7 dermatome ipsilateral to the cold pressor pain. The size (power) of the brain potentials to individual stimuli could be measured and was correlated to the intensity of the cold pressor pain (VAS score). During the onset phase of cold pressor pain, there was a decrease in power of the individual brain potentials evoked from the C7 dermatome contralateral to the cold pressor pain but the potentials, evoked from the C7 dermatome ipsilateral to cold pressor pain, were decreased more. The overall rating of the laser-induced pain intensity showed that the perceived intensity was lowest when evoked from the dermatome concurrently exposed to cold pressor pain. PMID- 1735414 TI - Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet. AB - It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735415 TI - Do muscle fibre size and fibre angulation correlate in pennated human muscles? AB - Several studies have reported estimations of the total number of fibres in a muscle, e.g. before and after training or before and after inactivity. In those investigations a combination of computed tomographic estimations of muscle size and morphological studies of fibre size has most often been used. There have been doubts about the reliability of those studies on pennate muscles, since changes in muscle fibre size have been said to alter fibre angulation and thus the number of fibres that will cross a section. If such an alteration in fibre angulation takes place with an increase in fibre size, there ought to be some correlation between fibre size and fibre angulation. The present study was designed to test whether repetitive estimations of muscle fibre angulation could be performed in vivo and if any such correlation could be found between fibre size and fibre angulation. A group of 15 women volunteered to take part in the study. Repeated ultrasonographic recordings were made on five subjects on 3 consecutive days to test the repeatability of ultrasonographic measurement of fibre angulation. Both muscle morphological analyses and ultrasonographic measurements of fibre angulation were performed on the other 10 subjects. Ultrasonographic measurement of fibre angulation was found to be reproducible since no variation between measurements made on different days was found. When trying to correlate muscle fibre size to the muscle fibre angulation, measured ultrasonographically, no significant correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735416 TI - Effect of endurance training on excessive CO2 expiration due to lactate production in exercise. AB - We attempted to determine the change in total excess volume of CO2 output (CO2 excess) due to bicarbonate buffering of lactic acid produced in exercise due to endurance training for approximately 2 months and to assess the relationship between the changes of CO2 excess and distance-running performance. Six male endurance runners, aged 19-22 years, were subjects. Maximal oxygen uptake (VO2max), oxygen uptake (VO2) at anaerobic threshold (AT), CO2 excess and blood lactate concentration were measured during incremental exercise on a cycle ergometer and 12-min exhausting running performance (12-min ERP) was also measured on the track before and after endurance training. The absolute magnitudes in the improvement due to training for CO2 excess per unit of body mass per unit of blood lactate accumulation (delta la-) in exercise (CO2 excess.mass-1.delta la-), 12-min ERP, VO2 at AT (AT-VO2) and VO2max on average were 0.8 ml.kg-1.l-1.mmol-1, 97.8 m, 4.4 ml.kg-1. min-1 and 7.3 ml.kg-1.min-1, respectively. The percentage change in CO2 excess.mass-1.delta la- (15.7%) was almost same as those of VO2max (13.7%) and AT-VO2 (13.2%). It was found to be a high correlation between the absolute amount of change in CO2 excess.mass-1.delta la-, and the absolute amount of change in AT-VO2 (r = 0.94, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735417 TI - Day-to-day changes in oxygen uptake kinetics at the onset of exercise during strenuous endurance training. AB - The aim of this study was to assess the effect of strenuous endurance training on day-to-day changes in oxygen uptake (VO2) on-kinetics (time constant) at the onset of exercise. Four healthy men participated in strenuous training for 30 min.day-1, 6 days.week-1 for 3 weeks. The VO2 was measured breath-by-breath every day except Sunday at exercise intensities corresponding to the lactate threshold (LT) and the onset of blood lactate accumulation (OBLA) which were obtained before training. Furthermore, an incremental exercise test was performed to determine LT, OBLA and maximal oxygen uptake (VO2max) before and after the training period and every weekend. The 30-min heavy endurance training was performed on a cycle ergometer 5 days.week-1 for 3 weeks. Another six men served as the control group. After training, significant reductions of the VO2 time constant for exercise at the pretraining LT exercise intensity (P less than 0.05) and at OBLA exercise intensity (P less than 0.01) were observed, whereas the VO2 time constants in the control group did not change significantly. A high correlation between the decrease in the VO2 time constant and training day was observed in exercise at the pretraining LT exercise intensity (r = -0.76; P less than 0.001) as well as in the OBLA exercise intensity (r = -0.91; P less than 0.001). A significant reduction in the blood lactate concentration during submaximal exercise and in the heart rate on-kinetics was observed in the training group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735418 TI - Determinants of isometric muscle strength in men of different ages. AB - Values of maximal isometric strength of five muscle groups and associated factors including occupational status, life style and health were studied in three groups of men aged from 31 to 35, 51 to 55, and 71 to 75 years. The results indicated significant differences between the age groups in isometric handgrip, elbow flexion, knee extension, trunk extension and trunk flexion strength. In the youngest group, the manual workers tended to have higher strength values in all muscle groups than the lower and higher status white collar workers, whereas among the middle-aged and oldest men the manual workers tended to have the poorest performance. Good self-rated health and the intensity of physical exercise during leisure were positively associated with muscle strength in the youngest and middle-aged groups whereas in the oldest group the most important variable was home gymnastics. The multivariate structural equation models of isometric strength differed somewhat among the age groups and in these models the above-mentioned variables accounted for from 33% to 43% of the variance in isometric strength within the age groups. The results illustrated the most important factors associated with isometric strength in samples of men of different ages and also provided suggestions as to how these determinants might influence comparisons between different age groups in respect of muscle strength. PMID- 1735420 TI - Blood flow through the ophthalmic veins during exercise in humans. AB - The blood from the face flows into the intracranium through the ophthalmic veins when human subjects become hyperthermic. To investigate a possible mechanism underlying this change in direction of flow, five young men were subjected to either passive body warming or exercise on a cycle ergometer, in a climatic chamber whose air temperature and relative humidity were 28 degrees C and 40%. Tympanic (Tty) and oesophageal temperatures, forehead sweat rate (msw), skin blood flow (Qsk) and blood flow through the ophthalmic vein (Qov) were measured, and the mean skin (Tsk) and mean body (Tb) temperatures were computed. Passive body warming was induced by a box-shaped body warming unit enclosing all but the subject's head. Exercise was performed either at an intensity of 60% maximal oxygen consumption or with the intensity increasing in increments. During both tests, msw and Qsk started to increase shortly after the imposition of the heat load. The Qov began to change with the venous blood flowing from the face into the intracranium and a complete reversal in the direction of Qov (from the face to the intracranium) came significantly later than the increases in msw and Qsk. The Tty at the time of flow reversal was the same in both tests. The Tsk (and hence Tb) at flow reversal was, however, significantly higher during passive body warming than during exercise. The mechanism for switching the direction of Qov appeared to have been triggered by a high temperature in the brain, and not by thermal input from the periphery of the body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735419 TI - Changes in sex hormone binding globulin, high density lipoprotein cholesterol and plasma lipids in male cyclists during training and competition. AB - This study was performed on 13 professional race-cyclists to examine changes in sex hormone binding globulin (SHBG), high density lipoprotein cholesterol (HDL-C) and serum lipid concentrations after training and after competition. While SHBG, total cholesterol and phospholipids increased and free fatty acids (FFA) decreased significantly during training, HDL-C and FFA increased and SHBG and triglycerides (TG) decreased significantly during the competition period. These latter changes in serum lipids and lipoproteins were assumed to be a direct effect of utilisation of muscle and plasma TG as fuels for exertion occurring only in extreme exercise. Changes in SHBG concentrations indicated that they were dependent on the conditions of the physical effort and could be related not only to the concentrations of androgens but also to the reduction in body mass. PMID- 1735421 TI - The primary structure of fatty-acid-binding protein from nurse shark liver. Structural and evolutionary relationship to the mammalian fatty-acid-binding protein family. AB - The primary structure of a fatty-acid-binding protein (FABP) isolated from the liver of the nurse shark (Ginglymostoma cirratum) was determined by high performance tandem mass spectrometry (employing multichannel array detection) and Edman degradation. Shark liver FABP consists of 132 amino acids with an acetylated N-terminal valine. The chemical molecular mass of the intact protein determined by electrospray ionization mass spectrometry (Mr = 15124 +/- 2.5) was in good agreement with that calculated from the amino acid sequence (Mr = 15121.3). The amino acid sequence of shark liver FABP displays significantly greater similarity to the FABP expressed in mammalian heart, peripheral nerve myelin and adipose tissue (61-53% sequence similarity) than to the FABP expressed in mammalian liver (22% similarity). Phylogenetic trees derived from the comparison of the shark liver FABP amino acid sequence with the members of the mammalian fatty-acid/retinoid-binding protein gene family indicate the initial divergence of an ancestral gene into two major subfamilies: one comprising the genes for mammalian liver FABP and gastrotropin, the other comprising the genes for mammalian cellular retinol-binding proteins I and II, cellular retinoic-acid binding protein myelin P2 protein, adipocyte FABP, heart FABP and shark liver FABP, the latter having diverged from the ancestral gene that ultimately gave rise to the present day mammalian heart-FABP, adipocyte FABP and myelin P2 protein sequences. The sequence for intestinal FABP from the rat could be assigned to either subfamily, depending on the approach used for phylogenetic tree construction, but clearly diverged at a relatively early evolutionary time point. Indeed, sequences proximately ancestral or closely related to mammalian intestinal FABP, liver FABP, gastrotropin and the retinoid-binding group of proteins appear to have arisen prior to the divergence of shark liver FABP and should therefore also be present in elasmobranchs. The presence in shark liver of an FABP which differs substantially in primary structure from mammalian liver FABP, while being closely related to the FABP expressed in mammalian heart muscle, peripheral nerve myelin and adipocytes, opens a further dimension regarding the question of the existence of structure-dependent and tissue specific specialization of FABP function in lipid metabolism. PMID- 1735422 TI - Purification, primary structure and molecular cloning of a rat ribosomal protein showing homology with yeast ribosomal protein YL34. AB - 1. A new 17-kDa mammalian ribosomal protein (PR17) was purified to homogeneity from the rat exocrine pancreas. The purification procedure was based on acidic extraction of a heat-denatured homogenate, ammonium-sulfate precipitation, hydrophobic chromatography on phenyl-Sepharose and analytical reverse-phase HPLC on mu Bondapak C18. Fractions of interest were collected using an antiserum directed against the first (1-14) moiety of somatostatin (1-28). 30 micrograms pure RP17 were obtained from 1 g fresh pancreas. 2. A short 111-b cDNA encoding RP17 was amplified from rat pancreatic first-strand cDNA template by using two 64 fold degenerate heptadecamer primers in the DNA-polymerase-chain reaction. From the sequence of amplified cDNA, an unambiguous oligonucleotide probe was designed to screen a rat pancreatic cDNA library. A cDNA clone coding for RP17 was isolated, whose nucleotide sequence, with an open reading frame coding for 155 amino acids (molecular mass of 17,199 Da), confirmed the partial amino acid sequences directly obtained from the purified protein. 3. Northern-blot analysis showed that a similar 0.75-kb transcript was present in rat pancreas, in the rat pancreatic acinar cell line AR 4-2J and in the human neuroblastoma cell-line NB OK-1, the highest level being in the latter two preparations, despite similar levels of RP17 in all three preparations, as tested with a rabbit antiserum directed against purified RP17. 4. The N-terminal sequence of both RP17 and the ribosomal protein YL43 from Saccharomyces cerevisiae (39 amino acid residues) showed a high degree of identity (77%), indicating that RP17 is a mammalian homolog of yeast ribosomal protein YL43. PMID- 1735424 TI - Identification of specific carboxyl groups on Anabaena PCC 7119 flavodoxin which are involved in the interaction with ferredoxin-NADP+ reductase. AB - Flavodoxin from the nitrogen-fixing cyanobacteria Anabaena PCC 7119 forms an electron-transfer complex with ferredoxin--NADP+ reductase (FNR) from the same organism. The complex is mainly governed by electrostatic interactions between side-chain amino groups of the reductase and carboxyl residues of flavodoxin. In order to localize the binding site on flavodoxin, chemical modification of its carboxyl groups has been carried out. Treatment of flavodoxin with a water soluble carbodiimide, N-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), in the presence of a nucleophile, glycine ethyl ester, caused a time-dependent modification of the protein that is responsible for the loss of its ability to participate as electron carrier in the photoreduction of NADP+ by chloroplast membranes, and also in NADPH--cytochrome-c reductase activity, by about 85%. Nevertheless, the ability of flavodoxin to receive electrons from the reducing side of photosystem I was much less affected. The inhibition was enhanced at low pH, suggesting that carboxylic acid groups were the target of chemical modification. Treated flavodoxin failed to form covalent complexes with FNR and the dissociation constant for the non-covalent complex with FNR was fourfold higher. After tryptic digestion of a sample of flavodoxin modified by EDC in the presence of [1-14C]glycine ethyl ester, two major radioactive peptides were isolated. The first protein fragment contained three carboxylic residues (Asp123, Asp126 and Asp129), corresponding to the region where long-chain flavodoxins show an insert compared to short-chain flavodoxins. The second peptide corresponded to a similar region, either in the amino acid sequence or in the three-dimensional structure of the protein and also containing three carboxyl groups (Asp144, Glu145 and Asp146). Four of these carboxyl groups (Asp123, Asp126, Asp144 and Asp146) are highly conserved in all long-chain flavodoxins, suggesting that they could play an essential role in substrate recognition. PMID- 1735423 TI - Interaction of the low-molecular-mass, guanine-nucleotide-binding protein with the actin-binding protein and its modulation by the cAMP-dependent protein kinase in bovine platelets. AB - Platelets have been shown to possess several, different, low-molecular-mass, guanine-nucleotide-binding proteins (G-proteins) with molecular masses about 20 30 kDa. We report here that a 25-kDa G-protein copurified with the bovine platelet actin-binding protein (ABP), a cross-linker of actin filaments which is known to generate the three-dimensional network of actin. Both the G-protein and ABP were recovered in a fraction that was insoluble in Triton X-100 and were extracted in 0.6 M NaCl. Gel-filtration chromatography of the high-salt extract and rechromatography in a low-salt solution indicated that the two proteins may be associated with each other. The association of the two proteins was suggested by cosedimentation of the G-protein with the actin gel formed by actin and ABP. The amounts of the cosedimented G-protein and ABP was unaffected by guanosine-5' O-[beta-thio]diphosphate and guanosine-5'-O-[gamma-thio]triphosphate, but the G protein, not ABP, was partially released from the actin gel by phosphorylating ABP with cAMP-dependent protein kinase. Thus, the association of the two proteins was affected by modification of ABP, but not by modification of G-proteins. The physiological significance of the possible association of the two proteins might be that the membrane skeleton functions as a modulator of the G-protein, rather than that the G-protein modulates the function of the membrane skeleton which comprises ABP. PMID- 1735425 TI - Localization of two interchain disulfide bridges in dimers of bovine alpha s2 casein. Parallel and antiparallel alignments of the polypeptide chains. AB - Carboxymethylation of bovine skimmed milk with 14C-labelled iodoacetic acid followed by purification of the alpha s2-casein dimer showed that all four cysteine residues in the protein are engaged in disulfide linkages. Mass spectrometry and sequence analysis of cystine-containing tryptic peptides revealed the presence of two interchain disulfide bridges in the protein. Sequence analysis of disulfide-linked peptides resulting from an enzymatic cleavage between the bridges demonstrated that the individual chains in the dimers are either aligned in an antiparallel or a parallel orientation. The identity of some of the disulfide-linked peptides was further verified by performic acid oxidation followed by sequence analysis of the resulting peptides. PMID- 1735426 TI - 1-Deoxy-1-phosphatidylethanolamino-lactitol-type neoglycolipids serve as acceptors for sialyltransferases from rat liver golgi vesicles. AB - 1-Deoxy-1-phosphatidylethanolamino-lactitols (LacPtdEtns), 1-deoxy-1 phosphatidylethanolamino-sialyllactitols (NeuAcLacPtdEtns) and their corresponding N-acetylated derivatives were synthesized and characterized by fast atom-bombardment mass spectrometry (FAB MS). The neoglycolipids were used as acceptors for sialyltransferases from rat liver Golgi vesicles. Sialylation rates were as good as or even better than those obtained with the corresponding authentic acceptors lactosylceramide (LacCer) and ganglioside GM3. The sialylation of LacPtdEtns and NeuAcLacPtdEtns yielded sialyl and disialyl compounds, respectively, as shown by FAB MS analysis of the reaction products. The results of competition experiments indicate that the neoglycolipids and the authentic acceptors are sialylated by the same sialyltransferases. PMID- 1735427 TI - An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells. AB - A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose. This intestinal lectin molecule is also immunologically related to the previously described IgE-binding protein (epsilon BP) isolated from RBL cells, since it is recognized by antibodies raised against recombinant epsilon BP. This intestinal form of epsilon BP has a molecular mass of 17.5 kDa, which is much lower than that of its RBL cell analogue (31 kDa). The attachment of IgE to the mouse intestinal epithelium was demonstrated by immunohistochemistry, along with the presence of a corresponding mouse intestinal epsilon BP. The carbohydrate-dependent nature of this attachment was established by demonstrating that IgE binding to mouse epithelium was specifically abolished by lactose (4 mM) and by a blood-group-A-active tetrasaccharide (0.2 mM), but not by mannose (10 mM). Finally, the association of IgE with the mouse intestinal epithelium was prevented by competition with the purified IgE-binding lectin isolated from rat intestine. Although the physiological function of this intestinal protein is still unknown, the finding that IgE binds to a lectin in the intestinal epithelium pinpoints a possible novel mechanism for the regulation of IgE-mediated disorders, such as food allergy. PMID- 1735428 TI - Structure of yeast pGKL 128-kDa killer-toxin secretion signal sequence. Processing of the 128-kDa killer-toxin-secretion-signal-alpha-amylase fusion protein. AB - The linear double-stranded DNA plasmid pGKL1 in yeast encodes a killer toxin consisting of 97-kDa, 31-kDa and 28-kDa subunits. A 128-kDa protein precursor of the 97-kDa and 31-kDa subunits, was first synthesized with a 29-amino-acid extension at its NH2-terminus as a secretion signal sequence. In the present study, the property of this signal sequence was studied by the analysis of a fusion protein with mouse alpha-amylase. Using the secretion signal sequence of the killer protein, the mouse alpha-amylase was successfully secreted into the culture medium. An intracellular precursor form of alpha-amylase was identified and purified. Analysis of the NH2-terminal sequence of this precursor molecule indicated that it corresponded to the secretory intermediate (pro form) of alpha amylase with the removal of the hydrophobic segment (Met1-Gly16) of the secretion signal. Both the secretion of alpha-amylase into the culture medium and the detection of the pro-alpha-amylase species in the cells were prohibited by a sec 11 mutation, or by the conversion of Gly to Val at the 16th position of the secretion signal. These results strongly suggest that the cleavage occurs between Gly16 and Leu17 by a signal peptidase, and that this cleavage is required for the secretion of alpha-amylase into the medium. Based on the data from the NH2 terminal amino acid sequences of secreted alpha-amylases, we conclude that the 29 amino-acid secretion signal present in the 128-kDa killer toxin precursor protein is a prepro structure. PMID- 1735429 TI - The differential transcriptional activity of two amphibian U1 small-nuclear RNA genes correlates with structural differences in the proximal sequence element. AB - We previously analyzed the transcription of an axolotl U1 small-nuclear RNA (snRNA) gene (AmU1) by microinjection into Xenopus laevis oocytes. In such an assay, AmU1 showed a low template activity compared to that of an X. laevis U1 snRNA gene (XlU1B2). Swapping the proximal sequence element (PSE) with that of XlU1B2 was required for AmU1 to acquire a transcription level equal to that of XlU1B2. In the present work, we examine the functional importance of the nucleotides that are common or different in both PSEs with the aim of identifying which nucleotides within the Xenopus U1 PSE are critical for this enhancement of Ambystoma mexicanum U1 snRNA transcription. The PSE mutation analysis showed that the central, phylogenetically conserved C-58/C-57 doublet is absolutely required for U1 promoter activity. In the 3' portion of this element, a CGC to ATG change (positions -54/-52) which partially restores the XlU1B2 PSE sequence, enables the AmU1 gene to gain the same transcriptional activity as XlU1B2. Remarkably, in this clustered point mutation, the sole C-54 to A-54 change is sufficient to obtain this increased level. Therefore, the activity of the AmU1 gene in injected Xenopus oocytes is strongly affected by a single sequence difference between AmU1 and XlU1B2 PSEs. This finding underscores the crucial importance of the nucleotide identity at position -54 to the function of the Xenopus U1 PSE. PMID- 1735430 TI - Engineering mammalian aspartyl-tRNA synthetase to probe structural features mediating its association with the multisynthetase complex. AB - Aspartyl-tRNA synthetase from higher eukaryotes is a component of a multienzyme complex comprising nine aminoacyl-tRNA synthetases. The cDNA encoding cytoplasmic rat liver aspartyl-tRNA synthetase was previously cloned and sequenced. This work reports the identification of structural features responsible for its association within the multisynthetase complex. Mutant and chimeric proteins have been expressed in mammalian cells and their structural behavior analyzed. A wild-type rat liver aspartyl-tRNA synthetase, expressed in Chinese hamster ovary (CHO) cells, associates within the complex from CHO cells, whereas a mutant enzyme with a deletion of 34 amino acids from its amino-terminal extremity does not. A chimeric enzyme, made of the amino-terminal moiety of rat liver aspartyl-tRNA synthetase fused to the catalytic domain of yeast lysyl-tRNA synthetase, has been expressed in Lys-101 cells, a CHO cell line with a temperature-sensitive lysyl tRNA synthetase. The fusion protein is stable in vivo, does not associate within the multisynthetase complex and cannot restore normal growth of the mutant cells. These results establish that the 3.7-kDa amino-terminal moiety of mammalian aspartyl-tRNA synthetase mediates its association with the other components of the complex. In addition, the finding that yeast lysyl-tRNA synthetase cannot replace the aspartyl-tRNA synthetase component of the mammalian complex, indicates that interactions between neighbouring enzymes also play a prominent role in stabilization of this multienzyme structure and strengthened the view that the multisynthetase complex is a discrete entity with a well-defined structural organization. PMID- 1735431 TI - Functional study of the human thyroid peroxidase gene promoter. AB - Structure/function relationships in the human thyroid peroxidase gene promoter have been studied by deletion and mutation analyses and confronted with footprint patterns obtained with thyroid nuclear extracts and the purified thyroid transcription factor TTF-1. Crude nuclear extracts from dog thyroid primary cultures were shown to contain a binding activity recognizing the -119 to -105 segment of the promoter (coordinates relative to the transcriptional start site). Deletion, or site-directed mutagenesis of this segment dramatically reduced transcriptional activity in transient expression experiments on gene fusions of the thyroid peroxidase promoter and the growth hormone reporter. This binding activity was increased in nuclear extracts from thyrocytes cultured in the presence of the cAMP-agonist forskolin. A mutation that decreased the promoter function in forskolin-stimulated thyrocytes resulted in weakening of the corresponding footprint. The binding site displays no significant sequence similarities with known cAMP-responsive elements. Mutagenesis of another region of the promoter (-99 to -94) induced the binding of an additional factor, resulting in a dramatically enhanced promoter activity. We show that the thyroid specific transcriptional factor TTF-1 is not directly involved in the above mentioned interactions and provide evidence suggesting that, in spite of displaying a similar binding pattern to thyroperoxidase and thyroglobulin promoters in vitro, TTF-1 plays a less important role in the former. Altogether, our data delineate the minimal thyroid peroxidase gene promoter in the human and identify the binding sites of two trans-activating factors, one of them being potentially the mediator of a non-conventional cAMP control, independent of the cAMP-responsive element and factor AP-2. PMID- 1735432 TI - Photoaffinity labelling of cholinesterases. Discrimination between active and peripheral sites. AB - Two para-dialkylaminobenzenediazonium salts, the dimethylamino (A) and dibutylamino (B) derivatives, are presented as structural probes for acetylcholinesterase and butyrylcholinesterase. While being reversible competitive inhibitors in the dark, A and B behave, upon irradiation and through the formation of arylcation species, as irreversible labels of ammonium-binding sites of both enzymes. The observed variations of the different inactivation rate constants point to a different structural environment for acetylcholinesterase binding and butyrylcholinesterase-binding sites. Moreover, in the case of acetylcholinesterase, protection experiments with specific ligands (edrophonium and propidium) showed that the dimethylamino salt A exclusively labels the hydrolytic anionic site, whereas the dibutylamino salt B also labels the peripheral site. Specificities and stoechiometries of the incorporations were determined and, in the case of acetylcholinesterase, the irradiated protein was submitted to chemical degradation. Peptide maps were obtained by gel-permeation chromatography and HPLC, giving access to labelled peptides which belong either to the active or to the peripheral site. PMID- 1735433 TI - Three-dimensional 15N-1H-1H and 15N-13C-1H nuclear-magnetic resonance studies of HPr a central component of the phosphoenolpyruvate-dependent phosphotransferase system from Escherichia coli. Assignment of backbone resonances. AB - We have performed three-dimensional NMR studies on a central component of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli, denoted as HPr. The protein was uniformly enriched with 15N and 13C to overcome spectral overlap. Complete assignments were obtained for the backbone 1H, 15N and 13C resonances, using three-dimensional heteronuclear 1H NOE 1H-15N multiple quantum coherence spectroscopy (3D-NOESY-HMQC) and three-dimensional heteronuclear total correlation 1H-15N multiple-quantum coherence spectroscopy (3D-TOCSY-HMQC) experiments on 15N-enriched HPr and an additional three dimensional triple-resonance 1HN-15N-13C alpha correlation spectroscopy (HNCA) experiment on 13C, 15N-enriched HPr. Many of the sequential backbone 1H assignments, as derived from two-dimensional NMR studies [Klevit, R.E., Drobny, G.P. & Waygood, E.B. (1986) Biochemistry 25, 7760-7769], were corrected. Almost all discrepancies are in the helical regions, leaving the published antiparallel beta-sheet topology almost completely intact. PMID- 1735434 TI - Localization of a vitamin-D-binding protein interaction site in the COOH-terminal sequence of actin. AB - The serum vitamin D binding protein is the carrier of vitamin D and its derivatives in the plasma. One of the known roles of this protein is to sequester monomeric actin in the blood, therefore implicating this protein in actin elimination. However, its binding site at the surface of actin is poorly delimited. We report here the results of a study which locates, using several actin fragments together with immunological probes, a vitamin D binding protein site near the COOH-terminal extremity. Thus, the interface is delimited by the sequence 360-372 in subdomain I of actin. PMID- 1735435 TI - Chemical modification of cholecystokinin-A receptors in rat pancreatic membranes. AB - Chemical modification of amino acids was used to probe the molecular structure of the cholecystokinin-A (CCK-A) receptor on rat pancreatic membranes. Radioligand binding studies with [3H]N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4 benzodiazepin-3- yl)1H- 2-carboxamide [(+/-)-[3H]L-364,718], a tritiated highly potent CCK-A receptor antagonist, enabled the evaluation of the effects caused by the modifying reagents. The apparent fragility of the receptor protein necessitated the development of a modification procedure without wash and centrifugation steps. Treatment of a concentrated membrane preparation with the group-specific agents N-ethylmaleimide, phenylglyoxal and diethylpyrocarbonate, subsequent dilution and incubation at lower temperatures (20 degrees C instead of the more generally used 37 degrees C) proved successful. All modifiers affected the binding characteristics for both agonists and antagonists considerably. CCK-A receptor coupling to guanosine-nucleotide-binding proteins was substantially diminished upon modification with N-ethylmaleimide and diethylpyrocarbonate, as could be concluded from the effects on the (+/-)-[3H]L-364,718 displacement by the cholecystokinin C-terminal octapeptide (CCK-8). The ligand-binding site was affected by all three reagents, as could be inferred from the specific protection obtained with the CCK-A receptor antagonist, lorglumide. It therefore appears that sulfhydryl, arginyl, and histidyl residues form an essential part of the ligand-binding domain on the CCK-A receptor and that sulfhydryl and histidyl residues are also involved in the signal-transduction pathway. PMID- 1735436 TI - Purification and characterization of F420H2-dehydrogenase from Methanolobus tindarius. AB - The oxidation of F420H2 (reduced coenzyme F420) is a key reaction in the final step of methanogenesis. This step is catalyzed in Methanolobus tindarius by the membrane-bound F420H2-dehydrogenase which was purified 31-fold to apparent homogeneity. The apparent molecular mass of the native enzyme was 120 kDa. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed the presence of five different subunits of apparent molecular masses of 45 kDa, 40 kDa, 22 kDa, 18 kDa and 17 kDa. The purified F420H2-dehydrogenase, which was yellowish, contained 16 +/- 2 mol iron and 16 +/- 3 mol acid-labile sulfur/mol enzyme. No flavin could be detected. The oxygen-stable enzyme catalyzed the oxidation of F420H2 (apparent Km = 5.4 microM) with methylviologen and metronidazole as electron acceptors at a specific rate of 13 mumol.min-1.mg-1 (kcat = 25.5 s-1). The isoelectric point was at pH 5.0. The temperature optimum was at 37 degrees C and the pH optimum at 6.8. PMID- 1735437 TI - Preparation and kinetic properties of 5-ethylphenazine-lactate-dehydrogenase-NAD+ conjugate, a semisynthetic lactate oxidase showing a hide-and-seek effect. AB - 5-Ethylphenazine-lactate-dehydrogenase-NAD+ conjugate (EP(+)-LDH-NAD+) was prepared by linking poly(ethylene glycol)-bound 5-ethylphenazine and poly(ethylene glycol)-bound NAD+ to lactate dehydrogenase. The average number of the ethylphenazine moieties bound per molecule of enzyme subunit was 0.46, and that of the NAD+ moieties was 0.32. This conjugate is a semisynthetic enzyme having lactate oxidase activity using oxygen or 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2H-tetrazolium bromide (MTT) as an electron acceptor; to make such conjugates seems to be a general method for artificially converting a dehydrogenase into an oxidase. When the concentration of oxygen or MTT is varied, the oxidase activity fits the Michaelis-Menten equation with the following kinetic constants: for the reaction system with oxygen, the turnover number per subunit is 2.3 min-1 and Km for oxygen is 1.91 mM; and for the system with MTT, the turnover number is 0.25 min-1 and Km for MTT is 0.076 mM. At the initial steady state of the oxidase reaction, only 2.1% of the NAD+ moieties of the conjugate are in the free state (i.e. not bound in the coenzyme-binding site of the lactate dehydrogenase moiety) and the rest are hidden in the coenzyme site; almost all the NAD+ moieties are in the reduced state. The apparent intramolecular rate constant for the reaction between a free NADH moiety and an oxidized ethylphenazine moiety is 2.3 s-1 and 2.1 s-1 for the systems with oxygen and with MTT, respectively. The apparent effective concentration of the free NADH moiety for the ethylphenazine moiety is 5.5 microM and is much smaller than that (0.34 mM) of the ethylphenazine moiety for the free NADH moiety; this difference is due to the effect of hiding the NADH moiety in the binding site, as the hidden NADH moiety cannot react with the ethylphenazine moiety. PMID- 1735438 TI - Principles for designing enzyme-like catalysts based on the rate-acceleration mechanisms of semisynthetic oxidases. AB - Combinations of substrate-binding sites and catalytic groups constitute various kinds of enzyme-like catalysts. The design of such catalysts can be evaluated by the enhancement of the overall catalytic activity by combining these parts into one catalyst. For a catalyst having one substrate-binding site and one catalytic group, an equation was obtained which shows the relationship between the rate acceleration due to the combination, the affinity of the site (1/Kd), intrinsic effective concentration (kin/kex) and substrate concentration ([S]). The intrinsic effective concentration is the ratio of the first-order rate constant (kin) of the intramolecular reaction between the catalytic group and the bound substrate and the second-order rate constant (kex) of the intermolecular reaction between the catalytic group and the free substrate; the value depends on the method of linking the catalytic group and the binding site. This equation provides the following principles for designing catalysts of this type with a considerable grade of rate-acceleration: [S] less than or equal to kin/kex and (1/10)[S] less than or equal to Kd less than or equal to kin/kex. To increase kin/kex, the structure of the binding site is required not to reduce the reactivity of the bound substrate, and the linker connecting the binding site and the catalytic group is required to be flexible and to have an appropriate length. A subunit structure is also found to be effective to improve the catalytic activity: the activity of an n-mer is at most n2 times as high as that of the monomer. As for the substrate-binding sites, the sites of natural enzymes and antibodies are good candidates because various kinds of binding sites with high affinity and specificity to the corresponding substrates are available. In addition, the equation relating the rate-acceleration with Kd, kin/kex, and [S] is used for explaining the catalytic efficiency of enzymes energetically. The principle for designing a multifunctional catalyst having several kinds of binding sites for its substrates and intermediates and several kinds of catalytic groups was then investigated. In this case, the diffusion of the intermediates strongly affects the activity of the multifunctional catalyst, and such a diffusion process was also analyzed. On the basis of these analyses, the following principles were obtained.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735439 TI - Dissection of the ribonuclease T1 subsite. The transesterification kinetics of Asn36Ala and Asn98Ala ribonuclease T1 for minimal dinucleoside phosphates. AB - Ribonuclease T1 contains a subsite which by interacting with the leaving nucleoside N of GpN dinucleoside phosphate substrates, contributes to catalysis [Steyaert, J., Wyns, L. & Stanssens, P. (1991) Biochemistry 30, 8661-8665]. The Asn36Ala and Asn98Ala mutations reduce the transesterification rates of GpA, GpC and GpU considerably whereas they have virtually no effect on the transesterification kinetics of the synthetic substrate guanosine 3'-(methyl phosphate) (GpMe) (in which the leaving nucleoside is replaced by methanol), indicating that the Asn36 and Asn98 side chains are part of the RNase T1 subsite [Steyaert, J., Haikal, A. F., Wyns, L. & Stanssens, P. (1991) Biochemistry 30, 8666-8670]. The kinetics of the Asn36Ala, Asn98Ala and wild-type catalyzed transesterification of guanosine 3'-(5'-D-ribosyl phosphate) (GpRib), another GpN analog in which the leaving groups is replaced by D-ribose, enables the mapping of the subsite interactions provided by Asn36 and Asn98. We find that the Asn36 amide function contributes 4.6 kJ/mol to catalysis through interactions with the ribose moiety of the leaving nucleoside. Asn98 is at least in part responsible for the subsite preference for cytidine; the Asn98 side chain preferentially binds cytosine as the leaving nucleoside base. PMID- 1735440 TI - New site-directed reversible inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase. AB - 1. CoA-thioether analogues of 3-hydroxy-3-methylglutaryl-CoA containing an additional methyl group at positions 2, 6(methyl at C3) or 4 of the acyl residue were prepared. To probe for hydrophobic interaction, their inhibitory properties were determined with 3-hydroxy-3-methylglutaryl-CoA reductase purified from baker's yeast. The CoA-thioethers were purely competitive inhibitors whose affinity to the reductase was near to that of the physiological substrate. 2. CoA sulfoxides derived from the CoA-thioethers displayed affinities to the reductase superior to that of the physiological substrate (Km = 7 microM). Depending on the degree of recognition of diastereomers by the enzyme, the inhibitor constants of the two best inhibitors vary from Ki = 200 nM and Ki = 80 nM (diastereomeric mixtures) to 25 nM and 20 nM, respectively (if only one diastereomer would interact with the enzyme). PMID- 1735441 TI - Mechanism of racemization of amino acids by aspartate aminotransferase. AB - Aspartate aminotransferase (mitochondrial isoenzyme from chicken) has been found to racemize very slowly dicarboxylic amino acid substrates in the presence of their cognate oxo acids [Kochhar, S. & Christen, P. (1988) Eur. J. Biochem. 175, 433-438]. Tyrosine, phenylalanine and alanine are racemized at the same rate although they undergo the transamination reaction 3-5 orders of magnitude more slowly than the dicarboxylic substrates. Similarly, the truncated enzyme aspartate aminotransferase-(27/32-410) catalyzes the racemization at the same rate as the native enzyme, while its rate of transamination is decreased to 3% of that of the native enzyme. Apparently, the rate-limiting step in racemization is not immediately linked to the transamination cycle. Decreasing the water concentration in the reaction medium by adding methanol at 0 degrees C drastically reduces the rate of racemization without affecting the rate of transamination. On the basis of these and additional kinetic data and the model of the three-dimensional structure of the active site, we conclude that a water molecule is responsible for the protonation of C alpha of the coenzyme-substrate intermediate from the wrong side. The diffusion of the water molecule into the interior of the enzyme appears to be the rate-limiting step in aspartate aminotransferase-catalyzed racemization. PMID- 1735442 TI - Purification and characterization of proteinase yscJ, a new yeast peptidase. AB - A newly recognized peptidase, designated proteinase yscJ, was purified from the yeast Saccharomyces cerevisiae. The enzyme is of non-vacuolar origin and cleaves the Tyr-Lys bond of the synthetic peptide substrate Cbz-Tyr-Lys-Arg-NH-Ph (Cbz, benzyloxycarbonyl; NH-Ph, 4-nitroanilide) and the Glu-Lys bond of the substrate Boc-Glu-Lys-Lys-NH-Mec (Boc, butoxycarbonyl; Mec, 4-methylcoumarinyl) with high efficiency. Optimum pH for cleavage of Cbz-Tyr-Lys-Arg-NH-Ph is in the range 7.0 7.5. The purified enzyme has a molecular mass of approximately 58 kDa, as judged by gel filtration on a Superose 12 FPLC column. Mercury compounds and EDTA were found to be potent inhibitors of proteinase yscJ activity. PMID- 1735443 TI - Extended type-1 chain glycosphingolipid antigens. Isolation and characterization of trifucosyl-Leb antigen (III4V4VI2Fuc3Lc6). AB - A Lewis-b-active glycosphingolipid containing a repetitive type-1 chain carbohydrate core was isolated from human colonic adenocarcinoma cell line Colo205. This glycosphingolipid was purified by HPLC and preparative high performance thin-layer chromatography and its structure elucidated by positive ion fast-atom-bombardment mass spectrometry with collision-induced disassociation, 1H-NMR spectroscopy and methylation analysis. The glycosphingolipid was found to be a trifucosylated derivative of this novel carbohydrate core, having the following structure: [formula; see text]. PMID- 1735444 TI - Primary structure and import pathway of the rotenone-insensitive NADH-ubiquinone oxidoreductase of mitochondria from Saccharomyces cerevisiae. AB - The gene encoding the yeast mitochondrial rotenone-insensitive internal NADH: ubiquinone-6 oxidoreductase has been sequenced. The DNA sequence indicates the presence of an open reading frame of 1539 bp predicted to encode a protein of 513 amino acid residues (57.2 kDa). The NADH dehydrogenase is synthesized as a precursor protein containing a signal sequence of 26 residues. In vitro import experiments show that the precursor NADH dehydrogenase is cleaved to the mature size by the matrix processing peptidase. Both cleavage and translocation across the mitochondrial membrane(s) are dependent on the membrane potential component of the proton-motive force. Comparison of the protein sequence of the yeast NADH dehydrogenase with the data bank indicates that the enzyme from yeast is homologous to the NADH dehydrogenase of Escherichia coli (22.2% identical residues). Both NADH dehydrogenases contain in the central part of the protein a sequence predicted to fold into a beta alpha beta structure involved in the binding of NADH or FAD(H2). Various aspects of the protein structure are discussed. PMID- 1735445 TI - Carnitine biosynthesis in hepatic peroxisomes. Demonstration of gamma butyrobetaine hydroxylase activity. AB - We have investigated whether hepatic peroxisomes are capable of synthesizing carnitine. When purified peroxisomes were incubated with gamma-butyrobetaine, a precursor of carnitine, formation of carnitine was observed. These results indicate that peroxisomes contain gamma-butyrobetaine hydroxylase, the enzyme which catalyzes the final step in the biosynthesis of carnitine. This enzyme was previously believed to be present only in the cytosol. gamma-Butyrobetaine hydroxylase activity in peroxisomes was not due to cytosolic contamination as evaluated by marker enzyme analysis. When proliferation of peroxisomes was induced by clofibrate treatment, gamma-butyrobetaine hydroxylase/mass liver increased by 7.6-fold and the specific activity by 2.5-fold. We conclude that hepatic peroxisomes synthesize carnitine and this synthesis becomes substantial under conditions of peroxisomal proliferation. PMID- 1735446 TI - Differential proteolytic sensitivity of yeast fatty acid synthetase subunits alpha and beta contributing to a balanced ratio of both fatty acid synthetase components. AB - The Saccharomyces cerevisiae genes FAS1 and FAS2 encoding the beta and alpha subunit of yeast fatty acid synthetase (FAS), respectively, were individually deleted by one-step gene disruption. Northern blot analysis of RNA from the resulting fas null allele mutants indicated that deletion of FAS2 did not influence the transcription of FAS1, while FAS2 transcription was significantly reduced in the delta fas1 strain. These data suggest an activating role of subunit beta on FAS2 gene expression or, alternatively, a repression of FAS2 by an excess of its own gene product. Compared to the intact alpha 6 beta 6 complex, the individual FAS subunits synthesized in the delta fas1 or delta fas2 strains exhibit a considerably increased sensitivity towards the proteinases present in the yeast cell homogenate. Using yeast mutants specifically defective in the vacuolar proteinases yscA (PRA1/ PEP4 gene product) and/or yscB (PRB1 gene product), it was shown that in vitro, subunit alpha is efficiently degraded by proteinase yscA while for degradation of subunit beta, the combined action of proteinases yscA and yscB is necessary. In vivo, besides the vacuolar proteinases, an additional proteolytic activity specifically affecting free FAS subunit alpha becomes increasingly apparent in cells entering the stationary growth phase. In contrast, under similar conditions uncomplexed FAS subunit beta is stable in strains lacking the vacuolar proteinases yscA and yscB. The reduced FAS subunit levels, at the stationary phase, were independent of the corresponding FAS transcript concentrations. Thus, differential degradation pathways are obviously removing an excess of either FAS subunit, at least under starvation conditions. A combination of both regulation of FAS gene expression and proteolysis of free FAS polypeptides may therefore explain the equimolar amounts of both FAS subunits observed in yeast wild-type cells. PMID- 1735447 TI - Biogenesis of the yeast vacuole (lysosome). Mutation in the active site of the vacuolar serine proteinase yscB abolishes proteolytic maturation of its 73-kDa precursor to the 41.5-kDa pro-enzyme and a newly detected 41-kDa peptide. AB - The codon of the catalytic serine in the active site of the vacuolar serine proteinase yscB (PrB) was changed to alanine, yielding the mutant gene prb1 Ala519. Following replacement of the wild-type PRB1 allele with prb1-Ala519, only a 73-kDa molecule was detected by immunoprecipitation with PrB-specific antiserum. The size of the mutant molecule corresponds to the unprocessed cytoplasmic precursor (pre-super-pro-PrB), as detected in sec61 mutants, when translocation into the endoplasmic reticulum is blocked. However, the mutant molecule is completely translocated into the secretory pathway, as indicated by protection from proteinase K digestion in spheroplast lysates in the absence of detergent. When N-glycosylation was inhibited in prb1-Ala519 mutant cells by tunicamycin, a smaller molecule of about 71 kDa appeared consistent with single N glycosylation and signal-sequence cleavage of the translocated mutant PrB molecule in the endoplasmic reticulum. Thus, the active-site mutation prevents the wild-type processing of the N-glycosylated 73-kDa precursor of PrB to the 41.5 kDa pro-PrB in the endoplasmic reticulum. In order to characterize the processing of wild-type super-pro-PrB in more detail, we generated antibodies against the non-enzymatic superpeptide domain of the 73-kDa precursor expressed in Escherichia coli. We find that, in addition to pro-PrB, a distinct protein (superpeptide) with a mobility of about 41 kDa in SDS/PAGE is generated in the endoplasmic reticulum. Pulse-chase experiments indicate rapid degradation of the 41-kDa superpeptide in wild-type cells. Correspondingly, the superpeptide was virtually undetectable by immunoblotting wild-type cell extracts. In contrast, no degradation of radioactively labeled 41-kDa superpeptide was observed within 60 min in mutant strains deficient in the vacuolar proteinase yscA (PrA), in which maturation of vacuolar pro-PrB to active PrB is blocked. Accordingly, superpeptide antigenic material was readily detected by immunoblotting cell extracts and enriched in vacuolar preparations of PrA deficient mutant cells. These results indicate that the superpeptide and pro-PrB travel to the vacuole, where the superpeptide is rapidly degraded upon pro-PrB activation to PrB. Using purified vacuoles, rapid degradation of the superpeptide was reconstituted in vitro by addition of either mature PrA or mature PrB. However, the PrA-triggered in vitro degradation of the superpeptide required PrB activity, as this process was inhibited in the presence of the PrB inhibitor chymostatin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735448 TI - Modifications of hepatic alpha-1-acid glycoprotein and albumin gene expression in rats treated with phenobarbital. AB - The serum level of alpha 1-acid glycoprotein (alpha 1-AGP) is significantly increased in various animal species by treatment with cytokines, glucocorticoids and phenobarbital. The mechanisms responsible for the cytokine-induced and glucocorticoid-induced increases are now well documented, but not so in the case of phenobarbital. The main purpose of this study was to assess whether phenobarbital acts on alpha 1-AGP synthesis in the liver at the transcriptional or translational level. Male Dark Agouti rats received 70 mg phenobarbital/kg daily for 7 days. The analysis of total hepatic RNA showed that a single injection of phenobarbital induced an 11-fold increase in phenobarbital-dependent cytochrome P450IIB mRNA, whereas seven injections of phenobarbital were required to induce a maximum 5.5-fold increase in alpha 1-AGP mRNA. Concurrently, the transcription rate of the alpha 1-AGP gene rose 3.5-fold. Hepatocytes isolated after the seventh injection of phenobarbital showed a threefold increased capacity to secrete alpha 1-AGP, corresponding to a 3.2-fold increased alpha 1 AGP mRNA content in the liver. In conditions in which its effect on the induction of alpha 1-AGP synthesis was maximum, phenobarbital caused a 30% reduction in liver albumin mRNA and in albumin secretion by isolated hepatocytes, resulting from a 60-70% reduction in the rate of transcription of the albumin gene measured in isolated nuclei. We conclude that the effect of phenobarbital on alpha 1-AGP and albumin gene expression occurs at the transcriptional rather than the translational level. PMID- 1735449 TI - Site-specific O-glycosylation of human granulocyte/macrophage colony-stimulating factor secreted by yeast and animal cells. AB - To compare the site specificity of O-glycosylation in lower and higher eukaryotes, we expressed human granulocyte/macrophage colony-stimulating factor (hGM-CSF) in the yeast Saccharomyces cerevisiae and in COS-1 cells. Analyses of specific hGM-CSF mutants secreted by yeast led to the conclusion that efficient O glycosylation in yeast requires residues S9 and T10. However, only S9 is used as an attachment point for an extended O-glycosyl chain in a 15.5-kDa hGM-CSF form. A 14.5-kDa hGM-CSF form, secreted by yeast, appears substituted by single mannosyl residues at both positions S9 and T10, indicating that O-glycosylation at T10 inhibits extension of the O-glycosyl chain attached to S9. As in yeast cells, the addition of O-glycosyl chains to hGM-CSF secreted by COS-1 cells requires the presence of S9 and T10 residues. These results demonstrate that, inspite of different biosynthetic routes, the selection of O-glycosylation sites is similar between lower and higher eukaryotes. PMID- 1735450 TI - Regulation of Schwann cell proliferation: mechanisms involved in peripheral nerve development. PMID- 1735451 TI - Cooperation of p53 and polyoma virus middle T antigen in the transformation of primary rat embryo fibroblasts. AB - Cell transformation in vivo seems to be a multistep process. In in vitro studies certain combinations of two oncogenes, a cytoplasmic gene product together with a nuclear gene product, are sufficient to transform primary rodent cells. Polyoma virus large T antigen can immortalize and, in cooperation with polyoma virus middle T antigen, transform primary cells. On the other hand mutant mouse p53 can also immortalize and, in cooperation with an activated Ha-ras oncogene, transform primary cells. In the present study we analyzed whether mutant p53 can replace polyoma virus large T antigen in a cell transformation assay with polyoma virus middle T antigen. Transfection of mutant p53 alone resulted in a cell line which had retained the actin cable network, grew poorly in medium with low concentration of serum, and failed to grow in semisolid agar. Cotransfection of mutant p53 together with polyoma virus middle T led to cells which grew in medium containing low serum concentration, grew well in semisolid agar, and displayed an altered morphology with the tendency to overgrow the normal monolayer. By these criteria these cells were considered fully transformed. The rate of p53 synthesis was similar in both cell lines. However, only p53 from the transformed cell line turned out to be stable. Cells transformed by mutant p53 and polyoma virus middle T expressed nearly the same amount of the c-src-encoded pp60c-src protein as cells transformed by the same p53 and cotransfected activated Ha-ras oncogene. However, only the polyoma virus middle T/p53-transformed cells exhibited an elevated level of pp60c-src-specific tyrosine kinase activity. Thus, despite different mechanisms leading to cell transformation, mutant p53 can replace polyoma virus large T antigen and polyoma virus middle T can replace the activated Ha-ras oncogene in cell transformation. PMID- 1735452 TI - Differential expression of PKC isoforms and PC12 cell differentiation. AB - Recent reports indicate that the protein kinase inhibitor H7 is capable of inducing both morphological and functional differentiation of a number of neural cell types. This investigation demonstrates that H7 potentiates the neurogenic properties of nerve growth factor (NGF) in PC12 cells with a concomitant change in the accumulation of the beta II-protein kinase C (beta IIPKC) isoform protein without changes in either alpha or gamma. However, NGF alone stimulates a coordinate increase in all three isoforms. The assay of acetylcholine esterase as a functional marker of neuronal differentiation demonstrates that H7 alone is not capable of stimulating morphological or functional differentiation in PC12 cells. H7 synergizes with NGF through a PKC-dependent pathway and by differential expression of PKC subtypes. The expression of the PKC transcripts for alpha, beta II, and gamma all undergo simultaneous yet differential changes in their patterns of expression during treatment with H7 and/or NGF. These data suggest that isoform switching is regulated primarily at the protein level. Last, these findings suggest that expression of PKC isoforms is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state. PMID- 1735453 TI - Dynamics of the dATP pool in cultured mammalian cells. AB - Conditions for labeling the dATP pool of V79 and 3T3 cells from [3H]deoxyadenosine (salvage) or [3H]adenine (via ribonucleotide reduction) were established. With deoxyadenosine the specific radioactivity of dATP reached a constant value after 60 min. In resting 3T3 cells this value was 30 times higher than in S-phase cells. Turnover of dATP and absolute rates of DNA synthesis and excretion of breakdown products of dATP were determined from the accumulation of isotope in various compartments and the specific activity of dATP. In S-phase cells the dATP pool had a half-life of 4 min, identical to that of dTTP determined earlier. Deoxyadenosine was the major breakdown product of dATP in the presence of an inhibitor of adenosine deaminase. The rate of deoxyadenosine excretion of V79 cells amounted to 4% of the rate of dATP incorporation into DNA. Inhibition of DNA replication increased deoxyadenosine excretion 5- to 10-fold, demonstrating a continued de novo synthesis of dATP, albeit at a slightly reduced rate. Our results fit a model involving a substrate cycle between dAMP and deoxyadenosine regulating the dATP pool, similar to the model of substrate cycles involved in the regulation of pyrimidine deoxyribonucleotide pools developed earlier. PMID- 1735454 TI - Expression of c-fos and c-jun mRNA in the developing chicken lens: relationship to cell proliferation, quiescence, and differentiation. AB - The in vivo developmental pattern of c-fos and c-jun mRNA expression has been examined in the embryonic chicken lens using a coupled reverse transcription/polymerase chain reaction assay. Levels of each mRNA were measured in the central epithelium, equatorial epithelium, and fiber cell mass at 6, 10, 14, and 19 days of development. The results showed that c-fos and c-jun mRNAs accumulated during development of the embryonic chicken lens epithelium as the proportion of proliferating cells decreased, suggesting that quiescent epithelial cells express high levels of both protooncogene mRNAs. Cells in the early stages of terminal differentiation near the lens equator also contained relatively high levels of c-fos and c-jun mRNA. As lens fiber cells matured, the number of copies of c-fos mRNA per cell decreased markedly, while c-jun mRNA increased. These findings demonstrate that c-fos and c-jun are differentially regulated during terminal differentiation of lens fiber cells and suggest that these protooncogenes are expressed in lens epithelial cells following cell cycle arrest. PMID- 1735455 TI - Stimulation of proliferation of HL60 cells by low concentrations of 12-O tetradecanoylphorbol-13-acetate and its relationship to the mitogenic effects of insulin. AB - The effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth and differentiation of cultured human acute promyelocytic leukemia (HL60) cells have been studied using cells growing in a fully defined medium consisting of RPMI 1640 supplemented with selenium dioxide, insulin, and either transferrin or ferric citrate. High concentrations of TPA (greater than 1 nM) cause the expected inhibition of proliferation and induction of macrophage-like differentiation. In contrast, in cells deprived of insulin, which continue to grow at a slow rate, lower concentrations of TPA stimulate proliferation without inducing differentiation. A TPA concentration between 0.03 and 0.3 nM will approximately double the long-term rate of thymidine incorporation into DNA and the rate of increase in cell density. Low-TPA becomes progressively less able to stimulate further proliferation as the insulin concentration is increased and is virtually without effect on cells stimulated by an optimal insulin concentration (5 micrograms ml-1). Insulin itself stimulates proliferation to a greater extent than low-TPA, increasing the long-term rate of thymidine incorporation and the rate of increase in cell density by three- to fourfold. The ability of higher concentrations of TPA to induce differentiation is independent of the presence of insulin. Low-TPA also stimulates the short-term incorporation of thymidine (during a 1-h pulse after 1 or 2 days incubation) by three- to fourfold, as compared to a sevenfold stimulation by insulin. The proliferation response to low TPA concentrations provides a useful model for dissecting the signalling pathways that control cell proliferation following stimulation by insulin and activators of protein kinase C. PMID- 1735456 TI - Mitogenic effects of bacterial neuroaminidase and lactosylceramide on human cultured fibroblasts. AB - Exogenously added bacterial neuraminidase and lactosylceramide both stimulated the growth of cultured human skin fibroblasts. Neuraminidase (100 units/ml) increased DNA synthesis 1.9-fold and cell density 1.4-fold after 24 and 48 h, respectively, in culture. Treated fibroblasts contained less ganglioside NeuAc alpha 2-3Gal beta 1-4GlcCer (GM3), presumably due to neuraminidase-catalyzed hydrolysis to lactosylceramide. Addition of lactosylceramide (100 microM) to the fibroblast culture medium also increased DNA synthesis threefold within 24 h and cell density twofold after 48 h. These findings are compatible with a mechanism by which the proliferation of human fibroblasts is regulated by the relative levels of GM3 and lactosylceramide in the plasma membrane. PMID- 1735457 TI - Role of spectrin in Amoeba proteus, as studied by microinjection of anti-spectrin monoclonal antibodies. AB - Spectrin is a major protein accounting for about 5% of whole-cell proteins in Amoeba proteus, and the precipitation of spectrin by intracellular injection of purified anti-spectrin monoclonal antibodies has a profound effect on cell morphology, motility, and movement-related cell activities in amoebae. Thus, amoebae injected with anti-spectrin antibodies show drastic changes in their shape and movement, suggesting that amoeba spectrin plays an important structural role, unlike nonerythroid spectrins in other cells. However, precipitation of spectrin does not affect the distribution of F-actin in amoebae. PMID- 1735458 TI - Internalization efficiency of the transferrin receptor. AB - Quantitative ultrastructural and biochemical methods have allowed us to obtain a coherent set of data on the internalization efficiency of the transferrin receptor (TfR). In confluent cell cultures we find that (1) the initial internalization rate of transferrin is approximately 10% per minute, and (2) around 10% of cell-surface TfRs are present in coated pits. From these data a lifetime of coated pits of ca. 1 min is derived. Furthermore, we show that coated pits constitute 1.1-1.4% of the plasma membrane area in confluent cell cultures. Thus, the TfR is concentrated six- to ninefold in coated pits compared to resident plasma membrane proteins. Moreover, we show that the concentration of TfRs in coated pits is cell density dependent, since only around 5% of the receptors are present in coated pits in low-density cultures. Correspondingly, the internalization of TfRs in high-density cell cultures is roughly twice as efficient as that in low-density cell cultures. The reduced TfR internalization efficiency at low cell density is accounted for by a concomitant decrease to 0.55% in the relative surface area occupied by coated pits. PMID- 1735459 TI - Differentiation of A31T6 proadipocytes to adipocytes: a flow cytometric analysis. AB - A flow cytometric assay has been developed which provides precise, quantitative information on the accumulation of cytoplasmic triglycerides in individual A31T6 proadipocytes as they differentiate into adipocytes. The opportunity to measure multiple optical parameters on a cell-by-cell basis has enabled us to monitor phenotypic aspects of differentiation with a greater level of sensitivity than was previously possible. Using the fluorescent hydrophobic probe, Nile red, we have found that as a cell proceeds along the differentiation pathway, the gold fluorescence signal from the cell increases, reflecting the accumulation of cytoplasmic lipid droplets. The value of the ratio of gold to red fluorescence defines a cell as being differentiated or undifferentiated. The greater resolution afforded by this cytometric method over more conventional approaches has allowed us to determine (1) the presence of an undifferentiated population of cells whose existence is not detected by conventional phase microscopy, (2) that insulin is not required to drive differentiation in this system, though the rate of differentiation is increased when the cells are exposed to insulin in combination with dexamethasone, (3) that exposure to a combination of insulin and dexamethasone results in a lower accumulation of lipid in a cell than does exposure to either agent alone, and (4) that A31T6 cells show the same response to differentiation-promoting agents whether applied at the time of plating or at confluence. PMID- 1735460 TI - The expression pattern of the pyruvate dehydrogenase E1 alpha subunit genes during spermatogenesis in adult mouse. AB - The expression patterns of the testis-specific and somatic forms of the pyruvate dehydrogenase (PDH) E1 alpha subunit genes were examined in adult mouse testis by in situ hybridization with specific cDNA probes and by immunostaining. A considerable increase in the mRNA level of the testis-specific PDH E1 alpha gene was observed in spermatocytes at the pachytene stage. The expression gradually decreased in spermatids as spermiogenesis progressed (especially after step 11) and it was not detectable in residual bodies. Transcripts of the testis-specific PDH E1 alpha gene were not identified in nongerminal Leydig and Sertoli cells. In contrast, the expression of the somatic form of the PDH E1 alpha gene was detected in spermatogonia, Leydig cells, and Sertoli cells at a low level. Transcripts of the somatic form of the PDH E1 alpha gene were not identified in other types of germ cells in adult mouse testis. Immunostaining with a PDH E1 alpha-specific antibody showed that the synthesis of PDH E1 alpha protein was dramatically increased in primary spermatocytes and that PDH E1 alpha protein existed abundantly in pachytene spermatocytes. The amount of PDH E1 alpha protein remained at a high level throughout spermiogenesis; however, it declined remarkably in epididymal spermatozoa. Leydig cells, Sertoli cells, and spermatogonia had low levels of PDH E1 alpha protein. These results suggest that (1) the transcription switch from the somatic form of the PDH E1 alpha gene to the testis-specific PDH E1 alpha gene occurs during the first meiotic prophase of spermatogenesis in adult mouse testis, and (2) PDH E1 alpha protein coded for by the testis-specific PDH E1 alpha gene is involved in the development of spermatogenic cells especially at stages after first meiotic prophase until the end of spermiogenesis in the testis. PMID- 1735461 TI - Distribution of the surface antigen HAM-4 and cytoskeleton during reformation of bile-canalicular structures in rat primary cultured hepatocytes. AB - The distribution of rat bile-canalicular surface antigen (HAM-4 antigen) and cytoskeletal elements (microtubules, actin filaments, and cytokeratin filaments) was examined during the reformation of bile-canalicular structures (BC structures) in primary cultures of dissociated hepatocytes obtained following collagenase perfusion. HAM-4 antigen, which initially dispersed after cell dissociation, became focused into regions of cell-to-cell contact even before formation of BC-structures. Typical bile-canalicular microvilli also appeared in these regions before the intercellular spaces were completely closed. Finally, after in vitro reformation of BC, HAM-4 antigen was localized specifically at the BC-surface. The process of BC-reformation and the intracellular organization of actin and cytokeratin filaments were not significantly affected by microtubule inhibitors (nocodazole, colcemid, and colchicine). However, the localization of HAM-4 antigen molecules at the surface of BC was disrupted by these inhibitors, suggesting that the distribution of HAM-4 antigen, which represents a marker for the reconstruction of surface polarity, is dependent on microtubule function. PMID- 1735462 TI - Cloned endothelium derived from autoimmune vascular disease retain structural and functional characteristics of normal endothelial cells. AB - MRL/1pr mice demonstrate anatomic specificity in their development of vasculitis including the small- and medium-sized muscular arteries of the mesentery. To define the functional role of endothelium in vasculitis, we have cloned endothelial cells derived from inflamed small- and medium-sized arteries. Primary cells were derived by enzymatic dispersement and endothelial cells were selected by utilizing a combination of specific culture conditions. Cloned endothelium were developed utilizing limiting dilution cultures supplemented by endothelial cell growth factor. The cloned endothelial cells express many structural features of mature endothelial cells including Factor VIII-RA, non-muscle-specific actin, and Weibel-Palade bodies. Functionally, the clones express functional receptors for the scavenger pathway for LDL metabolism. The cells do not express Class I MHC antigens; however, IFN-beta and IFN-gamma stimulate Class I MHC expression after 24 h, which induces lysis of virus-infected cloned endothelium by Class I restricted virus-primed T cells. In direct contrast to site-identical vascular smooth muscle cells (VSMCs), endothelial cells do not spontaneously express Class II MHC antigens, nor do they secrete biologically relevant levels of IL-1 unless triggered by lipopolysaccharide. The availability of site-specific cloned endothelium along with cloned VSMCs from autoimmune mice should resolve major experimental controversies involving the pathophysiology of inflammatory vascular disease. PMID- 1735463 TI - Identification and localization of a nucleolin homologue in onion nucleoli. AB - A protein homologous to nucleolin, a major nucleolar protein with multifunctional features involved in pre-rRNA synthesis and early processing, has been identified and localized in situ in onion root meristematic cells by different techniques, which have included the use of an antibody raised against hamster nucleolin. The protein was identified on Western blots of nucleolar proteins as a 64-kDa band, by means of the anti-nucleolin antibody, bismuth staining, and the silver staining-nucleolar organizer (Ag-NOR) method. The experiments also suggested that nucleolin could be a target of these two cytochemical stainings. Although the 64 kDa band corresponds to a major nucleolar protein, it is a minor one among total nuclear proteins. The same techniques were used in situ at the ultrastructural level, and the immunogold detection of the nucleolin homologue was quantitatively evaluated. The protein accumulates in the transition area from nucleolar fibrillar centers to the dense fibrillar component, which is considered to be the structural result of ribosomal gene transcription. Out of this transition area, the dense fibrillar component may be divided into two regions, proximal and distal with respect to fibrillar centers, which show, respectively, the significant and unsignificant presence of nucleolin; we interpret this fact as the expression of the topological arrangement of pre-rRNA processing. Fibrillar centers themselves showed a weak but significant labeling with the anti-nucleolin antibody. However, bismuth staining was absent from the interior of fibrillar centers, indicating that the nucleolin in them is not phosphorylated. Ag-NOR staining uniformly covered fibrillar centers and the dense fibrillar component (at least in its proximal region), but it did not stain condensed chromatin inclusions in heterogeneous fibrillar centers, showing that the binding of nucleolin to chromatin is associated with its decondensation. This work provides additional evidence of the high phylogenetic conservation of molecular motifs which take part in ribosome biogenesis. PMID- 1735464 TI - Cell growth inhibition by prostaglandin A2 results in elevated expression of gadd153 mRNA. AB - Treatment of Hela cells with prostaglandin A2 (PGA2) resulted in a marked inhibition of cell proliferation which was associated with a significant induction of gadd153 mRNA, a member of a novel class of genes associated with growth arrest and DNA damage. Induction of gadd153 mRNA was specific to prostaglandins capable of arresting cell growth and was dose-dependent with the maximum effect seen at 36 microM PGA2. Induction was rapid, occurring within 2-4 h and reaching a maximum by 8 h. These effects were reversible as removal of PGA2 resulted in a rapid decline in gadd153 mRNA levels coincident with resumption of cell growth. PGA2 induction of gadd153 mRNA was completely prevented by the presence of actinomycin D at a concentration sufficient to block transcription and was partially inhibited (50%) by the protein synthesis inhibitor cycloheximide. The presence of the protein kinase inhibitor 2-aminopurine decreased the PGA2 induction of gadd153 mRNA by greater than 90%, suggesting that cellular kinases play a role in the induction of gadd153 by PGA2. Thus PGA2 mediated growth arrest provides a useful model to further define the role of gadd153 in the negative control of cell growth. PMID- 1735465 TI - The epidermal growth factor receptor is associated with actin filaments. AB - In this paper we describe our investigations on the association of receptors for the epidermal growth factor (EGF) with the cytoskeleton of A431 cells. In order to determine which filamentous system the EGF receptors are associated to, the cytoskeletal fraction to which these receptors bind was isolated. Second, the possible colocalization of EGF receptors with different cytoskeletal elements was examined in A431 cells. By selective extractions of the A431 cytoskeletons, it is shown that more than 90% of the cytoskeleton-associated EGF receptors are removed from the cytoskeletons together with the actin filamentous system. During several cycles of poly- and depolymerization of actin isolated from A431 cells, the EGF receptor precipitates together with the actin containing filaments, indicating that EGF receptors are able to bind in vitro to actin filaments. With immunofluorescence studies we show that EGF receptors especially colocalize with actin filaments. These results demonstrate that the EGF receptor is associated specifically with actin filaments in A431 cells. PMID- 1735466 TI - Biochemical and behavioral recovery in a rodent model of Parkinson's disease following stereotactic implantation of dopamine-containing liposomes. AB - We have developed and characterized dopamine-containing liposomes which exhibited in vitro sustained release of dopamine for over 40 days. These liposomes were stereotactically implanted into the partially denervated corpus striatum of rats subjected to unilateral lesions of the substantia nigra. In vivo release of dopamine into striatal extracellular fluid was monitored by microdialysis and behavior was assessed by quantifying apomorphine-induced asymmetric rotation. Extracellular dopamine levels in the partially denervated striatum of the dopamine liposome-treated rats were greater than the levels in the lesioned rats which received control liposomes and these levels remained elevated for 25 days. In parallel, those rats which received dopamine liposomes exhibited partial behavioral recovery, with attenuation of asymmetric rotation following systemic apomorphine administration. These results suggest that dopamine-containing liposomes can partially ameliorate the deficits associated with a rodent model of Parkinson's disease, and demonstrate the potential of this technology as a method for the controlled delivery of therapeutic agents into discrete areas of the brain. PMID- 1735467 TI - Monoamine oxidases of the brains and livers of macaque and cercopithecus monkeys. AB - We assessed the two forms of monoamine oxidase (MAO), MAO-A and MAO-B, in discrete regions of the brain and in cerebral micro- and macrovessels, choroid plexus, and liver of three species of monkeys: African Green, rhesus, and cynomolgus. MAO was determined by specific [3H]pargyline binding which is stoichiometric and irreversible and by measuring the rate of oxidation of several substrates. Cerebral micro- and macrovessels had low MAO content. Regional brain MAO did not vary by more than one-fold in the brains of each of the three species of monkeys and was higher in the basal ganglia than in the cerebral cortex or cerebellum. MAO in the choroid plexus was low, while the liver had higher MAO activity than any of the brain samples. The vast majority of MAO in all the tissues that we examined was of the MAO-B type, and specific [3H]pargyline binding correlated well with the oxidation rate of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. These results show marked similarities in brain MAO distribution between monkey and man. Or the three monkey species, the African Green monkey had the lowest MAO activity in its cerebral microvessels, which constitute the blood-brain barrier, although the small number of observations in each group did not allow statistical analyses of the differences. PMID- 1735468 TI - Chronic intrastriatal injection of the excitatory amino acid receptor antagonist L-kynurenic acid in rat produces selective neuron sparing lesions. AB - Heritable neurodegenerative diseases may be associated with one or more endogenous neurotoxins whose actions on neurons lead to the degenerative changes. One metabolite of tryptophan, the amino acid L-kynurenic acid (L-KYN), was chronically injected into the striatum of the male rat to test its potential as an endogenous neurotoxin. L-KYN, at concentrations of approximately five times its normal brain levels, produced a large lesion with relative selective neuron sparing. The L-KYN-induced lesion presented three concentric regions: a central necrotic zone, a thin pyknotic zone, and an outermost spongiose zone. The number of GABA-ergic neurons were markedly reduced (approximately 76%), while cholinesterase-positive neurons were also lost. The NADPH diaphorase-positive neurons were the most resistant to L-KYN neurotoxicity and were spread throughout the spongiose zone. The brain levels of L-KYN are abnormal in patients with the neurodegenerative disorder Huntington's disease and as a neurotoxin L-KYN may play a role in the etiology of this disease. Of further significance, the fact that L-KYN is neurotoxic contraindicates the use of this excitatory amino acid receptor antagonist as a therapeutic agent in the treatment of neurodegenerative disorders. PMID- 1735469 TI - Differential distribution of parvalbumin-immunoreactive pericellular clusters of terminal boutons in developing and adult monkey neocortex. AB - Basket cells are GABAergic inhibitory interneurons and known regulators of pyramidal cells, the major class of excitatory neurons in neocortex. Parvalbumin (PV), a calcium binding protein, has been colocalized with GABA in cortical neurons (Celio, 1986. Science 231: 995-998) and has been reported to be present in the terminal boutons of basket neurons forming pericellular clusters in monkey neocortex (Hendry et al. 1989. Exp. Brain Res. 76: 467-472). In this study, we used immunohistochemical methods to evaluate the regional and laminar distributions of PV-immunoreactive (PV-IR) pericellular clusters of terminal boutons in the neocortex of neonatal, infant, adolescent, and adult rhesus monkeys. PV-IR pericellular clusters were composed of labeled terminal boutons that outlined the somata and proximal dendrites of large pyramidal neurons in layers III and V of primary motor cortex, layers V and VI of primary visual cortex, and layer V of visual association cortex (area 18). This laminar pattern was present in neonatal animals and did not change with age in motor cortex. However, in the visual regions of adolescent and adult animals, such PV-IR structures were not detected. PV-positive pericellular clusters were not observed in the prefrontal cortex at any age. The pattern of distribution of PV-containing pericellular clusters paralleled that of a subpopulation of pyramidal neurons containing nonphosphorylated neurofilament proteins (NFP); double labeling studies confirmed that a subgroup of NFP-positive pyramidal neurons were the targets of PV-IR pericellular clusters. The distribution of PV-IR pericellular clusters was compared to that of PV-IR terminal boutons of another class of interneurons, the chandelier cells. Terminal boutons of chandelier neuron axons align in vertical rod-like structures known as cartridges. Subpopulations of chandelier axon cartridges have been previously shown to be PV-IR and their distribution in visual and prefrontal cortices has been described (DeFelipe et al. 1989. Brain Res. 503: 49-54; Lewis and Lund. 1990. J. Comp. Neurol. 293: 599 615). These two types of structures composed of PV-IR terminal boutons tended to be present in different laminae in all regions and ages examined, except in layer III of primary motor cortex where both PV-IR pericellular clusters and chandelier cartridges were found. These findings indicate that in monkey neocortex PV immunoreactivity is present in pericellular clusters of terminal boutons that are likely to arise from basket cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735470 TI - Convergent inputs to single neurons in two different subdivisions of somatosensory forepaw digit cortex of the raccoon. AB - The aim of this study was to compare the physiological properties of single neurons in the glabrous (G) and heterogeneous (H) subdivisions of primary somatosensory digit 3 cortex of adult raccoons. Extracellular recordings were obtained from 50 G neurons whose receptive fields (RFs) were confined to the glabrous skin of a digit, and 41 H neurons whose RFs were located on hairy skin, claws, or mixtures of skin types. Both electrical and mechanical stimulation of the digits were used to assess excitatory neuronal responsiveness. The two sets of neurons, which had nearly identical depth distributions, differed considerably in their input convergence: (i) the percentage of neurons (%N) responding to electrical or mechanical stimulation of each off-focus digit and (ii) the number of digits from which individual cells could be driven were significantly greater for H neurons. Those G and H cells which could be excited by off-focus inputs were examined for probability of response (P), number of spikes per response (S/R), and latency of response (L) to digit stimulation. Surprisingly, for input from any one digit, there were no significant differences in these response properties between the two sets of neurons. However, inputs from different (on focus versus off-focus) digits varied significantly and revealed patterns of response properties that were qualitatively similar for both G and H neurons. Specifically, %N and P decreased while L increased symmetrically with distance of each off-focus digit from the central on-focus digit 3, reflecting corresponding variations in the synaptic accessibility and conduction time of off-focus excitatory inputs. In contrast, S/R values were very similar for all digits, suggesting that the synaptic strength of off-focus inputs is regulated independently of accessibility. Finally, preliminary findings indicated that denervation of the third digit caused a decrease in off-focus response latencies, while the normal latency profile across digits was retained. This suggests that the previously existing pattern of off-focus inputs to G and H neurons provides a template for denervation-induced cortical reorganization, whereby the synaptic efficacy of off-focus inputs is increased by disinhibition or facilitation. PMID- 1735471 TI - Experimental evidence of selective axonal regeneration in allogenic and isogenic Y-chambers. AB - Studies on axonal regeneration in Y-chambers over the past decade have consistently provided evidence of preferential growth toward a distal nerve piece. However, these findings are in contrast to the observations by Weiss and Taylor (1944. J. Exp. Zool. 95: 233-257), indicating that in fresh aortic Y chambers regenerating axons had no tendency to grow into a channel containing a distal nerve piece as compared to an open channel. The discrepancy between Weiss and Taylor's findings and those of later authors remains unexplained. In the present study we repeated the investigations by Weiss and Taylor, using both isogenic and allogenic aortic Y-chambers. In control groups the aorta graft was frozen and treated chemically to kill all cells and to deactivate possible growth factors of protein nature. In these groups preferential growth toward the distal nerve was pronounced although such specificity in growth was evident also in the nontreated types of aortic chambers. The findings do not support the results presented by Weiss and Taylor. PMID- 1735472 TI - Intracellular effects of QX-314 and Cs+ in hippocampal pyramidal neurons in vivo. AB - The effects of intracellular diffusion of the lidocaine derivative anesthetic QX 314 and of Cs+, which block Na+ and K+ conductances, respectively, were investigated in vivo in rat CA1 and CA3 pyramidal neurons to demonstrate slow Ca(2+)-related events. QX-314 loading prevented fast Na+ spikes, but slower presumably Ca2+ spikes remained. A slower and a faster duration type of QX-314 resistant spikes were observed. The former had high thresholds, while the latter was activated at moderate depolarized levels. The slower and the faster QX-314 resistant spikes fired at frequencies up to 8/s and 35/s and were 35-60 and 5-10 ms in duration, respectively. With Cs+ loading, pyramidal neurons depolarized and slow, presumably Ca2+, and fast Na+ spikes widened. Fast spikes usually showed a prominent shoulder and a slower repolarization. No differences were observed between drug effects in CA1 and CA3 neurons. In terms of their possible participation in theta rhythm genesis the slow QX-314-resistant events display the correct frequency and duration and can oscillate regeneratively. PMID- 1735473 TI - Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats. AB - This study examined the effects of 4-methylcatechol (4-MC), a nonamine catechol compound, on the neuropathic process of streptozotocin (STZ)-induced diabetic rats. 4-MC is one of the potent stimulators of nerve growth factor (NGF) synthesis at the cellular level and in cultured sciatic nerve segments of rats. Diabetic rats showed a statistically significant fall in sciatic motor nerve conduction velocity (MNCV) and a significantly reduced NGF content in the sciatic nerve (38.5 +/- 2.8% of control, P less than 0.01) during the experimental period of 4 weeks. 4-MC treatment of the diabetic rats for 4 weeks starting from the STZ injection elevated the NGF content (140% of untreated diabetic rats, P less than 0.05) and prevented the reduction in MNCV, but no effect on high blood glucose levels was seen. These findings suggest that decreased NGF levels in the sciatic nerve of the experimental diabetic rat may be involved in the development of the diabetic neuropathic process and that 4-MC, which can elevate endogenous NGF levels in vivo, may compensate for the inhibitory effect of STZ on the NGF level in progressive diabetic neuropathy. PMID- 1735474 TI - Protein kinase C activity and subcellular distribution in rat brain following repeated electroconvulsive seizures. AB - Protein kinase C (PKC) activity was measured in samples of neocortex, cerebellum, and hippocampus from adult rats receiving a series of 10 electroconvulsive seizures (ECS). Rats were sacrificed immediately and at various intervals from 15 min to 24 h after the last seizure. From 77 to 84% of total PKC activity was found in the cytosol versus the membrane fraction. PKC activity in cerebellum was significantly higher than in neocortex (15%, P less than 0.05). Repeated ECS treatment did not affect total PKC activity nor its distribution between membrane and cytosolic fractions when compared with sham ECS controls. This finding is in keeping with reports that adrenergic-stimulated phosphoinositol turnover is not altered 24 h following repeated ECS. PMID- 1735475 TI - Gestational hyperandrogenism. PMID- 1735476 TI - A step toward solving some of the problems of cryopreservation. PMID- 1735477 TI - In vitro fertilization in unstimulated cycles: the University of Southern California experience. AB - OBJECTIVE: To describe the clinical experience of our center with in vitro fertilization (IVF) in unstimulated cycles and to provide a comparison to stimulated cycles. DESIGN: Spontaneous ovulatory cycles were triggered with human chorionic gonadotropin in the midcycle, and 78 aspirations for IVF were performed, with the remainder of the IVF cycle proceeding in a standard manner. SETTING: The IVF program of the University of Southern California and the California Medical Center, Los Angeles, California. PATIENTS: Spontaneously ovulatory women (n = 46) with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTIONS: Human chorionic gonadotropin administration in midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURES: Embryo implantation and pregnancy. RESULTS: Seventy-eight follicle aspirations resulted in 11 clinical (14%) and 9 ongoing (12%) pregnancies. The per embryo implantation rate was 13% clinical and 11% ongoing. There was no decrease in per cycle pregnancy rates (PRs) for up to three unstimulated cycles. CONCLUSIONS: Unstimulated IVF is a viable alternative to stimulated cycles with PRs approximately one half those of stimulated cycles. It is reasonable to offer patients up to three cycles of unstimulated IVF without expecting a decrease in PRs. PMID- 1735478 TI - The predictive value of a single, early human chorionic gonadotropin measurement and the influence of maternal age on pregnancy outcome in an infertile population. AB - A single early quantitative hCG measurement 16 to 18 days after timed insemination has prognostic value with regard to pregnancy outcome in an asymptomatic, infertile population. Further, there is a statistically significant difference in the predictive value for hCG levels in patients less than or equal to 35 years compared with patients greater than 35 years of age. Interestingly, the same age-dependent phenomenon was observed when analyzing the predictive value of sonographically detected fetal heart motion at 5 weeks post-ovulation. We suggest that any investigation on pregnancy outcome, or its prediction should consider the impact of maternal age as a potentially significant covariate. PMID- 1735479 TI - An evaluation of Flowgel as an intraperitoneal barrier for prevention of postsurgical adhesion reformation. AB - Both Flowgel and Interceed(TC7) effectively inhibited postsurgical adhesion formation in the rabbit model. Given the unique handling characteristics of Flowgel, this material may have significant potential for use as an adjuvant in laparoscopic infertility procedures. PMID- 1735480 TI - The response of patients with polycystic ovarian disease to human menopausal gonadotropin therapy after ovarian electrocautery or a luteinizing hormone releasing hormone agonist. AB - OBJECTIVE: To compare the effect of ovarian electrocautery versus an intranasal (IN) luteinizing hormone-releasing hormone agonist (LH-RH-a) in the response of patients with polycystic ovarian disease (PCOD) to human menopausal gonadotropin (hMG) therapy. DESIGN: A prospective study with serial randomization of patients in two groups for treatment with ovarian electrocautery + hMG or LH-RH-a + hMG. SETTING: A teaching hospital reproductive endocrinology clinic. PATIENTS: Thirty three women with PCOD who failed to conceive after six treatment cycles with hMG. MAIN OUTCOME MEASURES: Midcycle and luteal phase endocrinology, ovulation, pregnancy rates (PRs), and miscarriage rates. RESULTS: There was no difference in the ovulation or PRs between the two groups. However, the number of cycles with multiple dominant follicles, the luteal phase serum testosterone, and the miscarriage rate were lower in the group pretreated with ovarian electrocautery. CONCLUSIONS: Pretreatment of patients with PCOD with ovarian electrocautery may be a better alternative to IN LH-RH-a therapy for induction of ovulation with hMG. PMID- 1735481 TI - Polycystic ovaries as a relative protective factor for bone mineral loss in young women with amenorrhea. AB - OBJECTIVE: To examine the impact of polycystic ovaries (PCO) on bone mineral density in amenorrheic women of reproductive age. DESIGN: A retrospective analysis and comparison of polycystic ovarian syndrome (PCOS) with non-PCOS amenorrheic women. A subgroup of patients with ultrasound (US)-diagnosed PCO was also investigated. SETTING: Specialist clinic in reproductive endocrinology. PATIENTS, PARTICIPANTS: Six hundred ten consecutive cases, mean age of 29.8 +/- 7.5 years, with current history of amenorrhea of various causes. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1 to L4) as measured by dual energy x ray absorptiometry, in relation to PCOS, US-diagnosed PCO, and US findings of normal ovaries. RESULTS: Amenorrheic patients with PCOS were found to be younger (P less than 0.001), with higher body mass index (P less than 0.001), were more estrogenized, as measured by endometrial thickness and uterine cross sectional area (P less than 0.001), and had higher bone mineral density (P less than 0.001) compared with non-PCOS amenorrheic patients. CONCLUSIONS: Patients with amenorrhea because of PCOS and those with US-diagnosed PCO have a higher bone density compared with amenorrheic patients with normal ovaries as detected by US scan. PMID- 1735482 TI - Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. AB - OBJECTIVE: To determine the effects of single dose tamoxifen on plasma estrogen (E)-binding equivalents and endometrial estradiol (E2) and progesterone (P) receptors. DESIGN: Controlled clinical study. SETTING: Normal human volunteers were studied in an academic research environment. PATIENTS: Premenopausal and postmenopausal women with histologically normal endometrium undergoing curettage or hysterectomy were selected. INTERVENTIONS: Tamoxifen was administered orally; blood and endometrial samples were collected 4 to 96 hours after tamoxifen administration. MAIN OUTCOME MEASURES: Plasma E-binding equivalents, endometrial cytosolic and nuclear E2 and P receptors. RESULTS: (1) Plasma E-binding equivalents increased eightfold at 4 to 24 hours of tamoxifen administration and declined exponentially thereafter, reaching control levels at 73 to 96 hours. Plasma E-binding equivalents were not affected by endogenous E2 levels. (2) Endometrial total E2 and P receptor levels increased in all women 2.9 to 19.2 fold after tamoxifen. (3) Tamoxifen resulted in an increase in the fraction of the E2 receptor measured in the nuclear extract 2.1 to 7.5-fold in midcycle, secretory, and menopausal endometria but not in proliferative endometrium. CONCLUSIONS: (1) Tamoxifen has an E2 agonistic effect on histologically normal human endometrium. (2) Irrespective of the total level of the endometrial E2 receptor, the nuclear capacity of that receptor in vivo is limited (approximately 75% to 80% of the total level). PMID- 1735483 TI - Cardiolipin antibody levels are not influenced by leukocyte immunotherapy in patients experiencing recurrent spontaneous abortion. AB - OBJECTIVE: To confirm that leukocyte immunotherapy stimulates the production of cardiolipin antibodies and to relate changes to pregnancy outcome. PATIENTS: Fifty patients with idiopathic recurrent abortion were studied. Thirty-six patients received injections of their partners' leukocytes; 14, injected with their own cells, served as controls. DESIGN: Cardiolipin antibodies were measured a month before and after leukocyte immunization. Patients who became pregnant were immunized a second time in early pregnancy, and cardiolipin antibodies were again measured a month later. RESULTS: Thirty-six patients immunized with their partners' leukocytes showed no appreciable change in cardiolipin antibody levels a month after vaccination. Twenty-nine of them subsequently became pregnant and were immunized again in early pregnancy: again, no change in cardiolipin antibody level was observed. There was no difference between the minority who aborted again and the majority who subsequently had successful pregnancies nor between those who responded to immunotherapy by producing cytotoxic antilymphocyte antibodies and those who did not. CONCLUSION: Leukocyte immunotherapy does not stimulate cardiolipin antibody production in women with normal pretreatment levels of the autoantibody. PMID- 1735484 TI - Long-acting oral bromocriptine (Parlodel SRO) in the treatment of hyperprolactinemia. AB - OBJECTIVES: To compare the effect of Parlodel SRO (Sandoz, Basel, Switzerland), a long-acting oral bromocriptine, to Parlodel (Sandoz) and to study the chronic effects of Parlodel SRO. DESIGN: The study was twofold: (1) random, double-blind and (2) open. SETTING: Patients were studied in an academic environment. PATIENTS: Hyperprolactinemic patients were selected. Sixteen patients were treated during 1 month. Ten patients completed the 1-year follow-up. INTERVENTIONS: Parlodel SRO or Parlodel was administered during 1 month (first 15 days: 5 mg/d; afterwards: 10 mg/d). Parlodel SRO was given during 1 year in variable doses (maximal 20 mg/d). MAIN OUTCOME MEASURES: Prolactin (PRL) levels, clinical improvement, and side effects were evaluated. RESULTS: After 1 month, 63% of the patients in both groups had normal PRL and 43% had menses. Side effects were similar. After 1 year all patients except one had normal PRL levels, and 89% were ovulating. CONCLUSIONS: The efficacy, tolerability, and long duration of action of Parlodel SRO make it an excellent alternative for the treatment of hyperprolactinemic patients. PMID- 1735485 TI - Evaluation of tubal patency by transvaginal sonosalpingography. AB - OBJECTIVE: To evaluate tubal patency by transvaginal sonosalpingography. DESIGN: Comparative study of transvaginal sonosalpingography with chromolaparoscopy in subjects with unknown tubal function. SETTING: Outpatient infertility clinic at Zeynep Kamil Maternity Hospital in Istanbul, Turkey. PATIENTS: Forty-two cases of unknown tubal function with infertility complaints were included. INTERVENTIONS: Isotonic saline was injected into the uterine cavity through a catheter. MAIN OUTCOME MEASURES: Transvaginal sonosalpingography is a safe, easy, and cost effective procedure for screening tubal status. RESULTS: The results obtained from transvaginal sonosalpingography and laparoscopy were completely consistent for 29 cases (76.32%) and partially consistent for 8 cases (21.05%). Transvaginal sonosalpingography accurately showed patency in 26 patients and bilateral nonpatency in 3 patients. CONCLUSIONS: Transvaginal sonosalpingography, with its accuracy and safety, is a promising screening and diagnostic technique in the evaluation of tubal patency on ambulatory basis. PMID- 1735486 TI - Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite. AB - OBJECTIVE: To determine the conceptional events resulting in a 46,XX/46,XY true hermaphrodite and to report the first pregnancy in a 46,XX/46,XY true hermaphrodite with an ovotestis. DESIGN: Chromosome studies were performed on patient lymphocytes and fibroblasts. Red cell antigens, human leukocyte antigens, and presence of Y-chromosome deoxyribonucleic acid were analyzed. Findings were compared with parental and sibling blood group data. SETTING: Genetics clinic and laboratories of a university hospital. RESULTS: These studies demonstrated that our patient is a chimera, with dual maternal and paternal contributions. In addition, despite the presence of an ovotestis, she conceived and delivered a child. CONCLUSIONS: The mechanism for chimerism in this case could be fertilization of (1) the secondary oocyte and first polar body; (2) the ovum and first polar body; (3) the ovum and second polar body; or (4) fusion of two embryos. PMID- 1735487 TI - Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment. AB - OBJECTIVE: To determine gender similarities and differences in perceptions of infertility and anticipated treatment stress in couples enrolling for in vitro fertilization (IVF) treatment. DESIGN: Both partners were evaluated at enrollment of IVF treatment. The evaluation was part of the screening procedure. SETTING: The Department of Obstetrics and Gynecology at a teaching hospital. PATIENTS, PARTICIPANTS: Two hundred consecutive couples who entered an IVF treatment program. MAIN OUTCOME MEASURES: Self-report questionnaire included items on the duration of infertility, degree of social support, effect of infertility on sexual relationship, expected likelihood of achieving pregnancy, anticipation of stress during treatment, and a self-rating scale of emotional reactions to infertility. RESULTS: The women anticipated more stress in IVF treatment but also rated greater degree of social support than the men. Both partners overestimated their chances of a successful treatment outcome. Factor analysis of the Infertility Scale produced three factors that were similar for both sexes. The first factor represented the desire to have a child as a major focus of life with inadequacy of the male role, social functioning and work efficiency, and pressure to have a child following. CONCLUSIONS: Women reported more stress, but the factors affecting stress of infertility were very similar for both partners. The intense focus on having a child was the predominant factor in anticipated stress of IVF treatment for both males and females. PMID- 1735488 TI - A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles. AB - OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination. PMID- 1735489 TI - Embryo implantation rates in oocyte donation: a prospective comparison of tubal versus uterine transfers. AB - OBJECTIVE: To compare pregnancy and implantation rates in tubal and uterine transfers during a hormonal replacement cycle in an oocyte donation program. DESIGN: Prospective randomized. PATIENTS: Forty-two consecutive patients who entered an oocyte donation program. INTERVENTIONS: Twenty-two patients were assigned for uterine transfer and 20 for tubal embryo transfer (ET). RESULTS: Twenty-three pregnancies were achieved, 12 (54.5%) after uterine transfers and 11 (57.9%) after tubal transfers. Implantation rates in both groups are not significantly different (17.4% uterine transfers versus 21.5% tubal ETs). CONCLUSIONS: Our results suggest that in hormonal replacement cycles (uniform endometrial stimulation) there is no advantage in transferring embryos to the fallopian tube. Furthermore, embryo quality and endometrial receptivity appear to be significantly more important than the time of entrance of an embryo to the uterine cavity in determining its chances of implantation. PMID- 1735490 TI - The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer. AB - OBJECTIVE: To assess whether a measure of uterine blood flow impedance (the pulsatility index, PI) as determined by transvaginal ultrasonography with color blood flow imaging, may be used to assess endometrial receptivity immediately before the time of embryo transfer (ET) after assisted conception. DESIGN: A prospective study of infertile women who had undergone treatment to induce multiple follicular development followed by ultrasound-guided oocyte retrieval. The oocytes were fertilized in vitro. SETTING: The Hallam Medical Centre. PATIENTS: Eight-two women (22 to 44 years of age) who all had three or four good quality embryos available for transfer to the uterus. INTERVENTIONS: All women were examined by transvaginal ultrasonography, with color flow imaging and blood flow analysis, immediately before ET. MAIN OUTCOME MEASURES: The mean PI of the left and right uterine arteries, the pregnancy rate (PR) (%), the embryo implantation rate (%), and the multiple PR (%). RESULTS: The patients were grouped according to whether the PI was low (1.00 to 1.99), medium (2.00 to 2.99), or high (3+). There were 27 women in the low PI group, 36 in the medium, and 19 in the high. The PR (%), embryo implantation rate (%), and multiple PR (%) were 41%, 15.3%, and 27.3% for the low PI group and 47%, 22.2%, and 47.1% for the medium PI group. There were no pregnancies in the high PI group. Thus 35% (19/54) of women who failed to become pregnant had a PI value greater than 3.0. CONCLUSIONS: These data suggest that the PI value on the day of ET could be used to: (1) increase the implantation rate by showing which embryos should be cryopreserved until the uterus is more receptive and (2) reduce the multiple PR by indicating that the number of embryos transferred should be limited when the uterus is most receptive. PMID- 1735491 TI - CA-125 is present in significant concentrations in periovulatory follicles of in vitro fertilization patients. AB - OBJECTIVE: To evaluate the presence of CA-125 in follicular fluid (FF) and its possible correlation to FF estradiol (E2), progesterone (P) and testosterone (T) and in vitro fertilization and embryo transfer (IVF-ET) outcome. DESIGN: Twenty eight patients undergoing IVF-ET were randomly chosen and 123 FF were sampled. SETTING: Clinical IVF-ET program and immunology laboratory for tumor diagnosis in a university tertiary care center. PATIENTS: Pure tubal factor patients treated by midluteal (long) gonadotropin-releasing hormone agonist protocol coupled with follicular phase human menopausal gonadotropin. INTERVENTIONS: Transvaginal follicular aspiration followed 48 hours later by ET. MAIN OUTCOME MEASURES: The 28 treatment cycles resulted in six gestations including five take-home infants. The mean levels (+/- SD) were 30.1 +/- 66.0 U/ML for CA-125, 28.5 +/- 58.1 ng/ML for E2, 2,360.5 +/- 2,846.3 ng/ML for P, and 7.22 +/- 7.08 ng/ML for T. The FF CA 125 levels were found to be widely divergent in different follicles of the same patient. There was no significant correlation between FF CA-125 and E2, P, T, oocyte fertilization, embryo quality, and pregnancy rates. CONCLUSIONS: CA-125 exists in significant amounts in FF of periovulatory follicles of IVF-ET patients. Intrafollicular CA-125 secretion is neither interrelated to follicular steroidogenesis nor is correlated to the outcome of IVF-ET. PMID- 1735492 TI - Primary testicular lesions in the twisted testis. AB - OBJECTIVE: To investigate primary lesions in twisted testes. DESIGN: The histologic study of testicular specimens obtained from men who had suffered testicular torsion. SETTING: The conditions required for material selection were the knowledge of the exact time of torsion and the presence of recognizable seminiferous epithelium cells. PATIENTS: Two hundred eighteen testicular torsions treated in La Paz Hospital, Madrid, Spain, from 1970 to 1990. MAIN OUTCOME MEASURES: After rejection of specimens that did not fulfill the conditions for selection, 109 biopsy and orchidectomy specimens from pubertal and adult males were studied to determine if primary lesions are superimposed to lesions secondary to anoxia. RESULTS: The following primary tubular lesions were found: (1) focal hypospermatogenesis (5 biopsies and 1 orchidectomy specimen; these testes showed degree I, II, or III anoxic lesions); (2) hypoplastic zones with only immature and hyperplastic Sertoli cells (3 orchidectomy specimens with degree III lesions); (3) zones of Sertoli-cell-only tubules that only contained a normal amount of mature appearing Sertoli cells (5 orchidectomy specimens with degree III lesions); and (4) intratubular calcifications (1 orchidectomy specimen with degree III lesions). In two cases with degree III lesions, more than one primary testicular lesion could be observed. CONCLUSIONS: An important number of twisted testes bear primary lesions that might had been involved in torsion development. The real percentage is probably even higher than that found in this study (14%) because the material obtained (biopsies) in many cases was insufficient to ensure complete exploration and because primary lesions are not recognizable in areas with pronounced anoxic lesions. PMID- 1735493 TI - Capacitated sperm cells react with different types of antisperm antibodies than fresh ejaculated sperm. AB - OBJECTIVE: To determine if sera of some women have antibodies against capacitated but not freshly ejaculated sperm. DESIGN: The sera of 66 women undergoing in vitro fertilization (IVF) were tested for sperm antibodies after 1 hour and 18 hours of sperm incubation in the maternal sera. Subsequently, 5 sera were tested with capacitated versus noncapacitated sperm cells. SETTING: The study was carried out in a university hospital department. PATIENTS, PARTICIPANTS: The patients were 66 consecutive couples undergoing IVF. INTERVENTIONS: Sera and semen that were taken for routine tests as part of the IVF procedures were used. MAIN OUTCOME MEASURES: A case with IVF failure associated with late appearance of sperm antibodies prompted us to study the detection of sperm antibodies after 1 hour and 18 hours incubation. RESULTS: Of 37 cases negative for sperm antibodies after 1 hour incubation, 7 demonstrated high levels of antibodies after 18 hours incubation. In 21 of 23 cases with low or intermediate levels of antibodies after 1 hour incubation, significantly higher levels (P less than 0.05) of antibodies were found after 18 hours. Different and higher levels of sperm antibodies were observed in five sera after incubation of 1 hour with capacitated sperm as compared with noncapacitated controls. CONCLUSIONS: Major antigenic differences may exist between capacitated and noncapacitated sperm. In some women sperm antibodies are reactive against capacitated sperm only. This has no certain clinical significance but may explain certain cases of IVF failure, unexplained infertility, and part of the variation in sperm antibodies testing methods. PMID- 1735494 TI - The relative distribution of viable sperm in the antegrade and retrograde portions of ejaculates obtained after electrostimulation. AB - OBJECTIVE: To determine the relative concentration, motility, and viability of spermatozoa in the antegrade and retrograde portions of the ejaculate after electroejaculation in spinal cord injured men. DESIGN: Retrospective. SETTING: University outpatient clinic providing tertiary care in reproductive rehabilitation. PATIENTS: The antegrade and retrograde portions of 22 ejaculates obtained from five spinal cord-injured men were analyzed for sperm density, mean sperm motility, and percentage of total motile and viable sperm yield. RESULTS: The number of spermatozoa were uniformly distributed between the antegrade (54.4%) and retrograde (45.6%) ejaculates. However, of the total sperm yield in both compartments, 66.3% of the motile spermatozoa and 71% of the viable sperm were found in the antegrade compartment (P less than 0.05). Additionally, mean sperm motility was significantly higher in the antegrade ejaculate (P less than 0.05). CONCLUSIONS: Significantly impaired sperm motility and viability are noted in the retrograde ejaculate. Efforts should therefore be directed to maximizing the antegrade portion of the electro-ejaculate and optimizing the technique of preserving functional sperm in the intravesical compartment. PMID- 1735495 TI - Formation of reactive oxygen species in spermatozoa of infertile patients. AB - OBJECTIVE: To determine the incidence of reactive oxygen species formation in semen of a population of patients consulting for infertility. DESIGN: The incidence of reactive oxygen species formation in whole semen and in washed spermatozoa was studied. The values obtained were correlated with semen parameters. The effect of the type of sperm washing on reactive oxygen species formation was also investigated. SETTING: Semen samples from patients consulting for infertility and control subjects were obtained by masturbation after 3 days of sexual abstinence. Reactive oxygen species formation was measured in whole semen, sperm suspension washed by Percoll gradients, or repeated centrifugations. Sperm motility parameters were measured by computer-aided sperm analysis. PATIENTS, PARTICIPANTS: Fertile control men and an unselected population of patients consulting for infertility. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Reactive oxygen species formation by fresh semen specimen or washed spermatozoa was measured in a computer-driven LKB 1251 Luminometer (LKB-Wallac, Turku, Finland). RESULTS: Reactive oxygen species formation was detected in 40% of the semen with spermatozoa from infertile patients, whereas none was found in 6 azoospermic men and 10 control men. The level of reactive oxygen species formation was inversely correlated to the semen volume, the percentage of motile spermatozoa, and sperm linearity both in semen and in Percoll-washed spermatozoa. Washing by repeated centrifugation-resuspension increased 20- to 50-fold sperm reactive oxygen species formation. This enhancement was caused by the centrifugation itself and by the removal of seminal plasma. Both morphologically normal and abnormal spermatozoa produced reactive oxygen species. CONCLUSION: The data suggest that reactive oxygen species formation by spermatozoa may be a significant cause for male infertility. PMID- 1735496 TI - The effect of tubal injection of methotrexate on fertility in the rabbit. AB - OBJECTIVE: To investigate the fertility of rabbits after tubal injection of methotrexate (MTX). DESIGN: The side of injection of MTX was randomly decided in a prospective experimental trial. PARTICIPANTS: Fourteen female New Zealand White Rabbits were believed to be of normal reproductive status. INTERVENTIONS: Methotrexate or Ringer's solution were injected into the tubes of the rabbits. The nidation index was used to measure the fertility of the animals. RESULTS: The average nidation index of the control tubes was not statistically different of the one of the tubes treated with MTX. CONCLUSION: Tubal injection of MTX has no adverse effect on fertility of rabbits. It seems ethical to investigate tubal injection of MTX as an alternative to laparoscopic management of unruptured ectopic pregnancy in the human. PMID- 1735497 TI - Preclinical models for human pre-embryo biopsy and genetic diagnosis. I. Efficiency and normalcy of mouse pre-embryo development after different biopsy techniques. AB - OBJECTIVE: To compare the usefulness of three micromanipulative methods at two different stages of pre-embryo development and to assess possible effects on postbiopsy survival and development. DESIGN: Four-cell and eight-cell mouse pre embryos were biopsied using enucleation, aspiration, or extrusion of single blastomeres. After biopsy, pre-embryos were observed for in vitro and in vivo development. SETTING: Laboratories of The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. PATIENTS, PARTICIPANTS: Only mice were used. INTERVENTIONS: Pre-embryo biopsy, developmental normalcy and pre-embryo transfer were studied. MAIN OUTCOME MEASURE(S): Few pre-embryos died as a result of biopsy trauma. High postbiopsy survival rates were associated with normal intrauterine and postnatal development. RESULTS: Expanded blastocyst formation rates from four-cell and eight-cell pre-embryos were 94.6%, 96.7% (controls); 80.7%, 89.1% (enucleation); 90.1%, 91.7% (aspiration); 83.1%, 91.5% (extrusion), respectively. Live birth rates at the four-cell stage were slightly lower in the enucleation group than in the blastomere aspiration and extrusion groups or controls (49.2% versus 58.8%, 56.3% and 66.7%, respectively). For the eight-cell stage, there were no differences between the groups. No developmental abnormalities were found in body or organ weights, in neonates or at 3 weeks of age, or in their subsequent ability to reproduce a second generation. CONCLUSIONS: Biopsy of mouse pre embryos produces only a small loss of viability because of trauma and permits normal prenatal and postnatal development among surviving pre-embryos. PMID- 1735498 TI - Preclinical models for human pre-embryo biopsy and genetic diagnosis. II. Polymerase chain reaction amplification of deoxyribonucleic acid from single lymphoblasts and blastomeres with mutation detection. AB - OBJECTIVE: To demonstrate the use of the polymerase chain reaction in the amplification of deoxyribonucleic acid (DNA) from single human lymphoblasts and mouse blastomeres. Amplified target genes for diagnosis of sickle cell anemia and Tay-Sachs are shown. Similarly, the sparce fur mouse model for ornithine transcarbamylase deficiency was used as an X-linked system for demonstration of mutation detection after biopsy of a single blastomere. A new diagnostic method for the detection of the ornithine transcarbamylase mutation using the restriction enzyme Mse I is presented. Accuracy and reproducibility were assured. DESIGN: Polymerase chain reaction proficiency test for amplification from single cells was studied. Also, accuracy of mutation detection systems was demonstrated. SETTING: Laboratories of The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. PATIENTS, PARTICIPANTS: We used the sparse fur mouse model and human blood cells. INTERVENTIONS: Pre-embryo biopsy, polymerase chain reaction amplification, and mutation detection were performed. MAIN OUTCOME MEASURES: Accuracy and reproducibility of DNA amplification without contamination, as well as efficient diagnostic analysis, from both single somatic and embryonic cells were shown. RESULTS: DNA amplification from single cells was uniformly rapid (6 to 10 hours) reproducible (n = 220) and accurate (n = 52). CONCLUSIONS: Our findings support the feasibility of clinical application for pre-embryo biopsy and genetic diagnosis of specific heritable diseases. PMID- 1735499 TI - Establishing a program of oocyte donation in Brazil. AB - Oocyte donation is a novel alternative for the treatment of patients who have infertility associated with ovarian failure. Both IVF-ET and GIFT represent new techniques of treatment for this group of patients. Synchronization between donor and recipient is very simple and also flexible. In our study population, four patients received oocyte or embryo donation after at least 20 days of E replacement, and two of them conceived a clinical pregnancy. Apparently, the flexibility of our protocol of E replacement allows an extension of the proliferative phase in cases that need to have additional time to synchronize the recipient's cycle to that of the donors. PMID- 1735500 TI - Ovulation induction in women with premature ovarian failure: a prospective, crossover study. AB - A prospective crossover study comparing ovulation induction techniques in eight women with premature ovarian failure is presented. These patients were treated with FSH rebound techniques using the GnRH-a, LA, alone in one treatment cycle and the same plus menopausal gonadotropins in the other treatment cycle. Two women ovulated in each group. We conclude that ovulation does occur in women with premature ovarian failure, but that luteal P may be inadequately secreted. PMID- 1735501 TI - Three-contrasts method hysteroscopy: the use of real-time ultrasonography for monitoring intrauterine operations. AB - Thirty-four patients were operated on by the technique of three-contrasts method hysteroscopy in this article. In three-contrasts method hysteroscopy, sonography guidance was used instead of laparoscopy guide. The distending medium introduced into the uterus during hysteroscopy and injected normal saline into the bladder and abdomen (which flowed into the posterior cul-de-sac) created these three contrasts. As a result, the walls of the uterus were clearly seen at sonography. Advantages and disadvantages of this technique have been described in detail. PMID- 1735502 TI - Serum relaxin concentrations in patients with out-of-phase endometrial biopsies. AB - When luteal phase relaxin concentrations were summed to give an integrated measure (pg/mL per cycle), relaxin was found to be significantly lower in those cycles with an out-of-phase endometrial biopsy. In addition, peak relaxin concentrations were lower in out-of-phase cycles compared with normal cycles. These data indicate that relaxin secretion may be related to normal luteal function and suggest that shortening of the luteal phase results in reduced relaxin production. Measurement of circulating relaxin may prove to be useful in making the diagnosis of out-of-phase biopsy and needs to be assessed for its usefulness in diagnosing abnormal luteal function. PMID- 1735503 TI - Serum progesterone and uterine curettage in differential diagnosis of ectopic pregnancy. AB - The implementation of a serum P less than 5.0 ng/mL is important because it resolves the differential diagnosis of EP by enabling timely uterine curettage. Curettage with examination of curettings or documentation of falling hCG can be used to prevent unnecessary laparoscopies in patients undergoing spontaneous abortions and can make possible definitive diagnosis and medical treatment of EP completely eschewing anesthesia and surgery. PMID- 1735504 TI - Ultrastructural aspects of endometrial surface in Kartagener's syndrome. AB - The endometrium of an infertile patient with Kartagener's syndrome showed initial secretory phase characteristics at SEM, whereas TEM analysis demonstrated several alterations in the central and peripheral microtubular distribution in 87% of the cilia examined. Such aspects seemed appropriate for a normal implantation, but the ciliary immotility or dyskinesia could cause an altered flow of the endometrial secretions and compromise the upstream movement of the spermatozoa. PMID- 1735505 TI - Peripheral T-lymphocyte activation and estrogen status. PMID- 1735506 TI - Clinical decision making: elevate or reduce to a science? PMID- 1735508 TI - Florida's IPN continues to be a forerunner in addressing nursing impairment. PMID- 1735507 TI - Clinical decision making: elevate or reduce to a science? PMID- 1735510 TI - Update on HIV/AIDS education requirement for re-licensure. PMID- 1735509 TI - Legislative assistant spends day with public health nurses. PMID- 1735511 TI - Implementation in Florida--one hospital's approach. PMID- 1735512 TI - Nurses to educate patients about end-of-life decisions. PMID- 1735513 TI - Medical complications of alcoholism. PMID- 1735514 TI - Alcoholism in the elderly. PMID- 1735515 TI - Eating disorders: a look at the basics. PMID- 1735516 TI - Shouldn't any research done by a nurse be considered nursing research? PMID- 1735517 TI - Colorectal cancer prevention: a primary care approach. AB - Colorectal cancer is a prevalent, deadly disease of the elderly. It is typically asymptomatic until advanced, and then responds poorly to treatment. Asymptomatic precursor lesions may afford both an opportunity to study carcinogenesis and to intervene and prevent cancer deaths. Prevention strategies focus on either primary prevention of polyps and cancers (mainly through dietary measures) and secondary detection and removal of precursor polyps and early cancers. Despite shortcomings in both strategies, dietary recommendations and screening tests for select patients may play an important role in reducing mortality. PMID- 1735518 TI - Geriatric primary care: a European perspective, Part II. AB - Europe is considered the parent of geriatric medicine, which was first recognized as a specialty in the United Kingdom. For the benefit of U.S. primary care physicians, GERIATRICS Editor-in-Chief Robert N. Butler, MD, convened a panel of leading European geriatricians in Lausanne, Switzerland, for a discussion of the successes and problems they are encountering in providing medical care to the aging world population. In Part I (Geriatrics 1992; 47 [Jan]:31-41) panelists described the healthcare services available to the elderly. In Part II, they discuss treatment and evaluation of dementia, use of hypnotics, rehabilitation approaches, and dietary and exercise recommendations for the elderly. PMID- 1735519 TI - Caring for nursing home patients: strategies to avoid conflict. AB - The need for primary care physicians to care for nursing home patients will continue to increase as America's population ages. Although some conflicts persist, nursing home practice can be gratifying for the physician if certain patient care strategies are followed. Measures that can help make the practice more efficient and rewarding include careful planning, setting limits on the practice, establishing patient goals early, developing a strong rapport with nursing home staff and patients' families, and gaining an understanding of local and federal regulations. Primary care physicians can also play a significant role in improving the quality of life for patients in this setting. PMID- 1735520 TI - Thyroid dysfunction: managing the ocular complications of Graves' disease. AB - The pathophysiology of Graves' orbitopathy has yet to be illucidated, but much can be done to reverse the potentially blinding effects of this debilitating ocular disease. Although only 5 to 10% of patients suffer severe ocular complications, many have significant signs and symptoms requiring ophthalmic medical and surgical intervention. Numerous systemic and topical therapies exist for all aspects of the ocular effects of hyperthyroidism, but clear clinical indications or advantages are lacking. Surgical therapies for residual abnormalities have solidified under recent clinical guidelines. PMID- 1735521 TI - Fibroproliferation in liver disease: role of monocyte factors. AB - Fibroproliferation was measured as the uptake of [3H]thymidine into fibroblasts. Human fibroblasts were incubated with 200 microliters monocyte-conditioned medium, the 0.22 microns filtrate from cultured monocytes, in Dulbecco's modified Eagle medium supplemented with controlled process serum replacement 2, a fetal calf serum substitute with low mitogenic activity. Increasing the numbers of fibroblasts resulted in a parallel increase in thymidine uptake to a maximal level. Fibroblasts (2 x 10(3] were plated into microwell plates and incubated with monocyte-conditioned medium for 72 hr. At 16 hr before harvest, 1 muCi [3H]thymidine was added. Cells were harvested with phosphate-buffered saline and washed, and the filters were counted. Fibroblasts incubated with Dulbecco's modified Eagle medium and controlled process serum replacement 2 showed minimal thymidine uptake. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes stimulated with 10 micrograms/ml lipopolysaccharides showed a sixfold increase in thymidine uptake over fibroblasts in Dulbecco's modified Eagle medium and controlled process serum replacement 2 alone. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte-conditioned medium from monocytes of patients with liver disease (n = 20) showed a 10-fold elevation in thymidine uptake compared with Dulbecco's modified Eagle medium and controlled process serum replacement 2. Results indicated that preincubation of monocyte-conditioned medium with either anti interleukin-1 beta (12.5 half-maximal units, 4 degrees C, 16 hr) or catalase (1,870 IU, 25 degrees C, 1 hr) did not alter the fibroproliferative activity of the monocyte-conditioned medium, suggesting that neither interleukin-1 beta nor activated oxygen intermediates were involved in fibroproliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735522 TI - Oral bile acid treatment and the patient with Zellweger syndrome. AB - The cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down-regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2-mo-old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition. PMID- 1735523 TI - Fragmentation of bile duct stones by extracorporeal shock-wave lithotripsy: a five-year experience. AB - Over 5 yr, 103 elderly patients (mean age = 70 yr) with bile duct stones (mainly not amenable to endoscopic extraction) underwent adjuvant extracorporeal shock wave lithotripsy using a first-generation kidney lithotripter. Disintegration of stones was achieved after a mean of 1.4 sessions in 92% of the patients. Spontaneous passage of fragments into the duodenum occurred in one fourth of the patients, and endoscopic extraction of fragments was necessary in 75% of the patients, resulting in complete clearance of the bile duct stones in 91 (88%) of 103 patients. The most important adverse effect was septic disease after extracorporeal shock-wave lithotripsy in 4% of the patients. The 30-day mortality rate was 1% (one patient), and another 15 patients died during a mean follow-up of 26 +/- 14 mo (mainly of causes unrelated to biliary tract disease). Two of 91 patients who had been rendered stone free were readmitted because of recurrent stone disease during the follow-up period. Of the 43 patients who still had their gallbladders during extracorporeal shock-wave lithotripsy, 14% subsequently underwent cholecystectomy. These data show that extracorporeal shock-wave lithotripsy of bile duct stones is a useful and safe adjunct to nonsurgical procedures for the removal of calculi in the biliary tree. PMID- 1735524 TI - Prognostic features and role of liver transplantation in severe corticosteroid treated autoimmune chronic active hepatitis. AB - To identify prognostic features and to define the role of liver transplantation in severe autoimmune chronic active hepatitis, findings before and after corticosteroid therapy in 111 patients were correlated with outcome and compared with the findings in 24 patients who had been selected independently for liver transplantation. Patients whose condition deteriorated during corticosteroid treatment were younger (32 +/- 3 yr vs. 43 +/- 2 yr; p less than 0.02) than those who experienced remission, but no individual features predicted outcome. Patients in whom therapy failed required longer durations of continuous treatment than did those who experienced remission (60 +/- 14 mo vs. 20 +/- 12 mo; p = 0.001). Of 13 patients who did not experience remission within 4 yr, 9 (69%) ultimately deteriorated. Ascites developed more often in those patients whose therapy failed and who died of liver failure than in counterparts who survived (86% vs. 33%). Patients undergoing transplantation were similar to those whose treatment failed, but they died less frequently (8% vs. 56%, p less than 0.01). Indeed, the 5-yr survival rate after transplantation was comparable to that of patients who had entered remission (92% vs. 100%). Successive biopsy samples failed to disclose recurrent autoimmune hepatitis after transplantation. Human leukocyte antigens A1, B8 occurred more commonly in patients in whom treatment failed or who underwent transplantation (70% vs. 41%, p less than 0.05). We conclude that failure to achieve remission within 4 yr and the human leukocyte antigen A1, B8 phenotype are associated with poor prognosis. Manifestations of liver decompensation, such as ascites, in patients who have been unable to experience remission justify consideration of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735525 TI - Portal-vein obstruction in children leads to growth retardation. AB - The portal vein is the main source of blood and hepatotrophic factors to the liver. Partial portal-vein ligation in rats results in reduced growth compared with that in control rats. To investigate whether extrahepatic portal vein obstruction occurring in early childhood influences growth in humans, anthropometric and nutritional assessments were prospectively carried out in 61 patients with extrahepatic portal vein obstruction. Comparisons were made with 183 matched healthy controls using National Center of Health Statistics reference. Fifty-one percent of children with extrahepatic portal vein obstruction had stunted growth (height for age less than 90% of normal), compared with 16% of controls (p less than 0.01). Growth retardation was severe in patients with longer (greater than 5 yr) than with shorter (less than 2.5 yr) duration of clinical portal hypertension (height for age, 88.0 +/- 3.2 vs. 95.1 +/- 3.0; p less than 0.01). Little difference was seen in the energy intake (1,302 +/- 463 kcal/day vs. 1,335 +/- 449 kcal/day; p = not significant) and weight for height index (83.6 +/- 9.3 vs. 88.0 +/- 7.9; p = not significant) between extrahepatic portal vein obstruction patients and controls. This suggested that despite comparable nutrition, marked growth retardation occurred in extrahepatic portal vein obstruction patients. Incremental growth velocity was studied in 31 patients; in 24 (73%) the baseline Z score (-2.1 +/- 0.2) had decreased further (-2.4 +/- 0.2) at the end of follow-up (15.5 +/- 1.6 mo). Although the incremental height velocity was only 56% of the expected height, incremental weight gain was 98% of the expected weight for the attained height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735526 TI - Isolated hepatic lipocytes and Kupffer cells from normal human liver: morphological and functional characteristics in primary culture. AB - The development of techniques for isolating hepatic lipocytes (Ito, stellate or fat-storing cells) from rodents has been instrumental in defining their role in hepatic vitamin A storage and fibrogenesis. In this study, we developed a method for the purification of lipocytes and Kupffer cell from wedge sections of normal human liver and examined their properties in primary culture. Sections of donor liver (400 to 600 gm) harvested but not used for transplantation were perfused in situ with University of Wisconsin solution and used for lipocyte isolation within 48 hr. Cells were isolated by catheter perfusion of the wedge through several large vessels with L-15 salts, Pronase and collagenase, followed by Larex density gradient centrifugation. Lipocytes were plated on either uncoated plastic or a basement membrane-like gel. Lipocyte and Kupffer cell yields were 2.3 +/- 0.6 x 10(5) and 8.6 +/- 1.4 x 10(5) cells, respectively, per gram of liver (n = 5). Lipocyte purity was 91% as assessed by vitamin A autofluorescence, and Kupffer cell purity was 83% as determined by uptake of fluorescinated staphylococci. Lipocytes cultured on the plastic spread within 48 to 72 hr, displaying slightly more heterogeneous retinoid droplet size than comparable rat cells; on a basement membrane gel, the cells remained aggregated and spherical with occasional spindlelike extensions. Lipocytes on plastic expressed procollagens I and III, collagen IV and laminin by immunocytochemistry, and types I, III and IV procollagen messenger RNAs by RNAse protection. Northern blot and polymerase chain reaction, respectively. Transmission electron microscopy of lipocytes at 7 days demonstrated a prominent rough endoplasmic reticulum and contractile filaments. Scanning electron microscopy revealed a smooth cell surface with perinuclear droplets beneath the cell membrane. With continued primary culture on plastic (more than 7 days), cells appeared "activated" (i.e., increased spreading and diminished retinoid droplets) and began proliferating as assessed by nuclear autoradiography and [3H]thymidine incorporation. Kupffer cells observed by scanning electron microscopy in early primary culture displayed prominent membrane ruffling and lamellipodia. In summary, we have established a reproducible method for the isolation and primary culture of human lipocytes and Kupffer cells. PMID- 1735527 TI - Drug-induced prolonged cholestasis in adults: a histological semiquantitative study demonstrating progressive ductopenia. AB - Drug-induced acute hepatitis may be followed by prolonged cholestasis despite the withdrawal of the drug. Eight patients suffering from prolonged cholestasis caused by several drugs were investigated with sequential liver biopsies. At the early stage, lesions of acute cholangitis were observed in most patients; at the chronic phase, ductopenia, defined by the absence of interlobular bile ducts in at least 50% of small portal tracts, was demonstrated in all patients. Ductopenia might be the consequence of acute cholangitis; the degree of ductopenia and the chronicity of the disease might be directly related to the severity of the early acute damage of bile ducts. Consequently, in patients with severe cholestasis related to drugs, research of early morphological signs of acute cholangitis and then of ductopenia seems to be important. PMID- 1735528 TI - High cardiac output of advanced liver disease persists after orthotopic liver transplantation. AB - This study measured cardiac output before and 1 or 2 yr after orthotopic liver transplantation in 23 patients. Cardiac output was measured by thermodilution before transplantation and by first-pass radionuclide angiocardiography at follow up. Study patients were selected as those doing well clinically and by standard laboratory tests at 1-yr and 2-yr reevaluations with no evidence of rejection: six had mild recurrent hepatitis shown on biopsy samples. Hepatocyte function was normal at the time of the study as shown by galactose elimination capacity of 442 +/- 90 mg/min. Medications were cyclosporine and prednisone in all patients, azathioprine in 10 patients and a combination of antihypertensive therapy to maintain diastolic blood pressure less than 90 mm Hg in 20 patients. Mean (+/- S.D.) pretransplantation cardiac output was 9.1 +/- 3.1 L/min and remained elevated at 8.3 +/- 2.1 L/min 1 yr, and 9.6 +/- 2.6 L/min (n = 13) 2 yr after transplantation. A significant (p less than 0.001) correlation was found between pretransplant and follow-up cardiac output. End diastolic, end systolic and stroke volumes are all increased in a pattern similar to that seen in end-stage cirrhosis. These data show that the high cardiac output of the hyperdynamic state of advanced liver disease persists after liver transplantation. The mechanisms and consequences of this require further study. PMID- 1735529 TI - Human leukocyte antigen typing of siblings in hereditary hemochromatosis: a cost approach. AB - To assess the clinical value of human leukocyte antigen typing in the diagnosis and management of hereditary hemochromatosis, 105 siblings of 35 proband cases of hemochromatosis were retrospectively analyzed to study whether the exclusion of human leukocyte antigen typing would have adversely affected management. All siblings and probands had already been tested for human leukocyte antigen-A and human leukocyte antigen-B typing, serum ferritin and transferrin saturation. The median age of siblings was 55 yr (range = 11 to 82). Siblings were categorized according to putative genotype (homozygote, heterozygote and normal) using human leukocyte antigen typing. Phenotypic expression of hemochromatosis was considered to be iron overload as indicated by an elevated ferritin (male = greater than 350 micrograms/L, female = greater than 200 micrograms/L) and/or transferrin saturation (greater than 55%). Six of 37 homozygotes had a normal ferritin and transferrin saturation, with five of these patients under 32 yr old. No putative heterozygotes with both an abnormal ferritin and transferrin saturation were seen, although 12 of 48 (25%) heterozygotes had either an elevated ferritin or transferrin saturation. Twenty of 20 normal siblings had a normal ferritin and transferrin saturation. To assess the cost of screening with and without human leukocyte antigen typing, a cost model simulation was used that compared the costs of both methods in a hypothetical family (proband, homozygote, heterozygote and normal sibling).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735530 TI - Effect of alpha-tocopherol on hepatic mixed function oxidases in hepatic ischemia/reperfusion. AB - This study was done to determine the relationship between microsomal lipid peroxidation during hepatic ischemia/reperfusion and alteration in cytochrome P 450-dependent drug metabolism. Rats were pretreated with alpha-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham ischemic animals. After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450 and mixed function oxidases were studied. In vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr (5,242 +/- 682 U/L) and were significantly reduced by alpha-tocopherol pretreatment (1,854 +/- 229 U/L, p less than 0.01). Similarly, microsomal lipid peroxidation was elevated in the vehicle-treated ischemic group, but this elevation was prevented by alpha tocopherol pretreatment. Microsomal cytochrome P-450 content and aminopyrine-N demethylase activity were both decreased in vehicle-treated ischemic rats to 60% and 70% of sham-ischemic control levels, respectively. Although alpha-tocopherol restored cytochrome P-450 content to the level of sham-ischemic control rats, aminopyrine-N-demethylase activity remained at 76% of control with alpha tocopherol treatment (p less than 0.01 compared with sham-ischemic control). In contrast to what was seen with cytochrome P-450 and aminopyrine-N-demethylase, aniline p-hydroxylase activity was elevated in the vehicle-treated ischemic rats compared with sham-ischemic control rats. These increases were prevented by alpha tocopherol pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735531 TI - Evidence that an iron chelator regulates collagen synthesis by decreasing the stability of procollagen mRNA. AB - Iron chelation has been shown previously to decrease collagen synthesis at a posttranslational level by inhibiting prolyl 4-hydroxylase, one of the key enzymes in collagen metabolism. On the other hand, recent in vivo studies of iron overload in rats suggest that iron could specifically activate collagen gene expression in liver tissues. These findings led us to investigate whether iron chelation might also affect collagen gene expression and posttranslational modification. Our data indicate that alpha,alpha'-dipyridyl, an iron chelator, at a concentration of 1 mmol/L, decreased steady-state levels of type I procollagen messenger RNA by 42% (p less than 0.001) without affecting beta-actin messenger RNA levels. Nuclear runoff studies demonstrated that transcription of the type I procollagen gene was unchanged by alpha,alpha'-dipyridyl. However, the turnover rate of type I procollagen messenger RNA was increased by 30%. This pretranslational inhibition of collagen synthesis was not due to decreased lipid peroxidation, because thiobarbituric acid-reactive substances were unchanged by alpha,alpha'-dipyridyl. However, cycloheximide totally abolished the effect, indicating that de novo protein synthesis was required. PMID- 1735532 TI - The effect of bile salts on carbonic anhydrase. AB - Bile salts are potent inhibitors of bovine carbonic anhydrase and human carbonic anhydrase I and human carbonic anhydrase II. To further characterize the binding of bile salts to carbonic anhydrase, rate constants for the CO2 hydration reaction in the presence of deoxycholate, cholate, glycocholate and taurocholate were determined using stop-flow experiments. Values for the Michaelis-Menton dissociation constant for bovine carbonic anhydrase, human carbonic anhydrase I and human carbonic anhydrase II were found to be 5.2, 9.2 and 13.2 mmol/L, respectively. The inhibition constant values for the various bile salts tested ranged from 0.1 to 1 mmol/L for bovine carbonic anhydrase, 1.6 to 2.4 mmol/L for human carbonic anhydrase I and 0.09 to 0.7 mmol/L for human carbonic anhydrase II. Our results suggest a mechanism of noncompetitive carbonic anhydrase inhibition for bile salts. Bile-salt binding to carbonic anhydrases as measured by scanning molecular sieve chromatography resulted in an increase in partition radius, molecular volume and surface area. The partition radius increased from 24 A to 28 A in the presence of 2.5 mmol/L sodium deoxycholate at critical micelle concentration. As determined by sedimentation equilibrium measurements, approximately 1 gm of carbonic anhydrase will bind 0.03 gm of deoxycholate, suggesting three to six binding sites for bile salt on the carbonic anhydrase molecule. The conformational changes and inhibition of carbonic anhydrases resulting from bile-salt binding may be important to the regulation of enzymatic activity in tissues along the enterohepatic circulation; by limiting bicarbonate availability this interaction may also contribute to the metabolic derangements seen in patients with cholestatic liver disease. PMID- 1735533 TI - S-adenosylmethionine protects against acetaminophen hepatotoxicity in two mouse models. AB - Because S-adenosylmethionine promotes synthesis of hepatic glutathione in chronic liver disease and is well tolerated in man, we investigated its use as an antidote to acetaminophen hepatotoxicity in two mouse models. In C57Bl6 mice, deaths were abolished by S-adenosylmethionine given within 1 hr of 3.3 mmol/kg body wt acetaminophen (0 of 32 vs. 13 of 49, p less than 0.005) and reduced if given 2 to 5 hours after acetaminophen administration (4 of 42 vs. 13 of 49, p less than 0.01). Mixed disulfate/tosylate salt of S-adenosylmethionine abolished mortality in C3H mice given 2 mmol/kg body wt acetaminophen (0 of 24 vs. 4 of 18; p less than 0.05). In both mouse models, S-adenosylmethionine reduced depletion of plasma (median = 20.8 mumol/L vs. 14.6 mumol/L) and liver glutathione (198% vs. 100%; p less than 0.05), liver damage and release of AST after acetaminophen administration. Pretreatment with buthionine sulfoximine, which inhibits glutathione synthesis, abolished the beneficial effect of S-adenosylmethionine on survival and plasma glutathione level. S-adenosylmethionine reduces acetaminophen hepatotoxicity by metabolism of the active moiety to glutathione. This benefit may last as long as 5 hr after acetaminophen ingestion. PMID- 1735534 TI - Influence of albumin on the net sinusoidal efflux of the organic anion dibromosulfophthalein from rat liver. AB - Besides being excreted into bile, several anionic drugs and anionic drug conjugates are excreted from liver into plasma by a carrier-mediated process (sinusoidal efflux). In the study presented here, we investigated the influence of albumin on the net sinusoidal efflux of an organic anion from isolated perfused liver, with net sinusoidal efflux defined as the resultant of efflux and reuptake. We tested the hypothesis that albumin exerts its effect on net sinusoidal efflux through inhibition of repeat uptake rather than on the sinusoidal efflux process itself. We also studied possible acinar heterogeneity in net sinusoidal efflux rate of the organic anion. Isolated rat livers were preloaded with the nonmetabolizable anionic model compound dibromosulfophthalein in the absence (type I) or presence (type II) of bovine serum albumin. Fluorescence microscopy of dibromosulfophthalein in liver sections showed selective zone 1 loading after type I loading and homogeneous acinar distribution after type II loading. The rate of net sinusoidal efflux and biliary excretion was then studied in single-pass perfusions with various concentrations of bovine serum albumin in the medium. Net sinusoidal efflux of dibromosulfophthalein showed a marked dependence on albumin concentration in both type I and type II experiments. Net efflux rate reached a maximal value at a medium concentration of 300 mumol/L bovine serum albumin and was not increased further at 600 mumol/L. The initial uptake rate of dibromosulfophthalein was not significantly different in the 300 mumol/L and 600 mumol/L bovine serum albumin experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735535 TI - Changes in transcripts of basement components during rat liver development: increase in laminin messenger RNAs in the neonatal period. AB - The expression of laminin and type IV collagen messenger RNA in rat liver was investigated in relation to liver development. Levels of messenger RNA for laminin chains A, B1 and B2, and alpha 1 and alpha 2 chains of type IV collagen were studied by Northern-blot and dot-blot analysis. Although the expression of messenger RNAs for laminin B1 and B2 chains was higher in 19-day gestational fetal liver when compared with the adult, the highest level was detected in 15 day newborns. This finding coincides with the final establishment of the mature liver. Laminin A messenger RNA was not detected in the 19-day gestational fetus or in the neonatal period. In contrast, alpha 1-(IV) and alpha 2-(IV) collagen messenger RNAs maintained high levels in the early neonate and then decreased gradually after 15 days. Our findings suggest that during late stages of liver ontogeny the main components of liver basement membrane proteins undergo a significant alteration in their synthesis. The data further suggest that laminin may play a role in the final stages of hepatic differentiation. PMID- 1735536 TI - Regulation of perfluorooctanoic acid--induced peroxisomal enzyme activities and hepatocellular growth by adrenal hormones. AB - A wide variety of compounds, including hypolipidemic drugs, plasticizers and other industrial chemicals, have been found to cause liver enlargement and hepatic peroxisome proliferation by mechanisms that are unclear. Although thyroid and sex hormones have been shown to modulate the hepatic response to these chemicals, the role of adrenal hormones in these phenomena is not clear, and a few studies have produced conflicting data. Therefore this study was undertaken to investigate the role of adrenal hormones in hepatomegaly and peroxisomal enzyme induction caused by peroxisomal proliferators and to further delineate the interrelationship between these parameters. Because adrenalectomy alters hepatic drug metabolism, we have used the nonmetabolizable proliferator perfluorooctanoic acid. Our data show that hepatomegaly caused by perfluorooctanoic acid depends on corticosterone, the major glucocorticoid in rodents. Liver growth caused by perfluorooctanoic acid appears to be predominantly hypertrophic in nature, and DNA synthesis in response to perfluorooctanoic acid predominates in periportal regions of the liver lobule. Data also show that although induction of peroxisomal beta-oxidation by perfluorooctanoic acid is independent of adrenal hormones, induction of catalase is dependent on the presence of these hormones. This study supports the contention that induction of activities of various peroxisomal enzymes is controlled by different regulatory mechanisms. PMID- 1735537 TI - Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats. AB - Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by 125I-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats. Experimental groups were studied from day 1 through day 4 after partial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 +/- 0.21 mm Hg.min.ml-1 x 100 gm vs. 5.19 +/- 0.16 mm Hg.min.ml-1 x 100 gm; p less than 0.01). Plasma volume increased significantly on day 2 (4.31 +/- 0.07 ml.100 gm-1 vs. 3.86 +/- 0.04 ml.100 gm-1; p less than 0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 +/- 0.08 ml.100 gm-1 vs. 3.73 +/- 0.03 ml.100 gm-1) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 +/- 0.6 ml.min-1 x 100 gm-1 vs. 25.5 +/- 1.2 ml.min-1 x 100 gm-1), iliac and mesenteric blood flow. On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the protal outflow block.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735538 TI - An improved model of acetaminophen-induced fulminant hepatic failure in dogs. AB - We have established an improved model of fulminant hepatic failure in dogs. Buthionine sulfoximine is used to inactivate glutathione synthesis, and small increments of acetaminophen are given intravenously to maintain the plasma level at approximately 200 micrograms/ml for 20 hr. This regimen produces severe liver injury along with many of the features seen in humans with acetaminophen poisoning. The first sign of impending liver failure is hypoglycemia. This occurs about 15 hr into the experiment and requires treatment with a continuous infusion of glucose. Between 15 and 20 hr, serum ALT activity begins to rise, indicating the onset of liver necrosis. Over the following 15 to 20 hr ALT activity continues to rise and is accompanied by an increase in bilirubin, a prolongation of the prothrombin time and the development of fetor hepaticus. Thirty to 48 hr after the initial acetaminophen dose, the animals begin to exhibit symptoms of encephalopathy and progress from lethargy to the inability to maintain posture and then coma, seizures and death. Liver biopsy specimens obtained at several stages throughout the study showed progressive necrosis, ultimately resulting in the complete destruction of zones 2 and 3. PMID- 1735539 TI - Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide. AB - Nitric oxide is a vasodilator tonically secreted by endothelial cells that is involved in the regulation of arteriolar tone. This study, which includes two protocols, was performed to investigate whether nitric oxide plays a role in the pathogenesis of arterial hypotension in cirrhosis with ascites. In protocol 1, the administration of increasing doses (25, 50, 250, 500 and 1,000 micrograms.kg 1.min-1) of the nitric oxide biosynthesis inhibitor N omega-nitro-L-arginine to 18 conscious rats with cirrhosis and ascites produced, at each dose tested, a significantly greater increase in arterial pressure than in 17 conscious control rats. At the lowest dose of N omega-nitro-L-arginine, arterial pressure significantly rose in cirrhotic rats but not in controls. In protocol 2, arterial pressure, estimated renal plasma flow, glomerular filtration rate and sodium excretion were measured in 12 cirrhotic rats with ascites and 10 control rats before and during the sequential infusion of previously selected doses of N omega nitro-L-arginine (25, 50 and 250 micrograms.kg-1.min-1). Changes in arterial pressure reproduced those observed in protocol 1. In control rats, N omega-nitro L-arginine caused a decrease in estimated renal plasma flow without affecting glomerular filtration rate or sodium excretion. In contrast, N omega-nitro-L arginine administration to cirrhotic animals did not produce any appreciable renal vasoconstrictor effect, and it increased glomerular filtration rate and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735540 TI - Treatment of refractory ascites: is dialytic ultrafiltration better than paracentesis? PMID- 1735541 TI - Pulmonary dysfunction in advanced liver disease. PMID- 1735542 TI - Lower rates of postbiopsy bleeding: needle vs. technique. PMID- 1735543 TI - Identification of genetic differences in debrisoquine hydroxylase activity. PMID- 1735544 TI - Data watch. Survey tracks hospital renovation activity. PMID- 1735545 TI - The sagging safety net. Emergency departments on the brink of crisis. AB - U.S. hospitals are facing an emergency care crisis. At the same time emergency departments are overflowing with uninsured patients seeking primary care, violence-related trauma cases are soaring, leaving underfunded trauma systems on the verge of collapse. In a special cover package, we explore the causes of the crisis, the current prospects for change, and related issues in emergency care today. Beginning on page 26, we present an overview of the crisis, with particular attention to the breakdown of trauma systems. Starting on page 30, we look at the growing threat of violence itself entering hospital EDs; on pages 34 35, we examine how hospitals are attracting and retaining critically needed clinicians, and how trauma systems are dealing with ongoing shortages of specialists. On pages 37-38, we explore the patient satisfaction question; and on pages 38-39, we present the latest data on emergency care utilization from the American Hospital Association. PMID- 1735546 TI - In a time of change, construction planning takes on complex new dimensions. AB - While construction budgets appear to be tighter in the wake of Medicare's fold-in of inpatient capital payment, hospitals are going ahead with ambitious plans for expansion and renovation. But construction planning is increasingly becoming more interwined with overall strategic planning. PMID- 1735547 TI - Business and labor move forward via joint health care reform plan. PMID- 1735548 TI - Direct contracting: employers look to hospital-physician partnerships to control costs. AB - Direct contracting is gaining popularity as employers seek new ways to control health care costs. Eliminating third parties like HMOs and PPOs can create long term savings, but it's much more complicated than many hospitals realize, experts warn. PMID- 1735549 TI - How to give MDs a greater role in management. PMID- 1735550 TI - Boards, execs more savvy about CEO contracts. PMID- 1735551 TI - Service basics attract new outpatient lab users. PMID- 1735552 TI - Poor HIS sales trigger reduced systems support. PMID- 1735553 TI - Credentialing program demise a 'disappointment'. PMID- 1735554 TI - Hospitals use employee opinion on job candidates. PMID- 1735555 TI - IRS, AMA limit hospital-MD joint ventures. PMID- 1735556 TI - Physician recruitment: a three-step strategy. PMID- 1735557 TI - DNA polymorphism of HLA class II genes in primary biliary cirrhosis. AB - We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary biliary cirrhosis (PBC) and in healthy Danes. The following genetic markers were found with increased frequencies in PBC: HLA-B8 (relative risk, RR = 2.4, P less than 0.05, 'corrected' P greater than 0.05), HLA-DR3 (RR = 3.4, P less than 0.01, 'corrected' P less than 0.05), the DRB3*01/02/03 (DRw52) associated DRB Bgl II 9.1 kilobase (kb) fragment (RR = 2.9; P less than 0.05, 'corrected' P greater than 0.05), the DQA1*0501 associated DQA Taq I 4.8 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05), the DQB1*0201 (DQw2) associated DQB Hin dIII 11.5 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC and B8, DR3, DQA1*0501, and DQB1*0201, which are frequently found together on the same haplotype, are at variance with recent reports on associations between PBC and Drw8. The discrepancy suggests that PBC is genetically heterogenous. PMID- 1735558 TI - Hemopoietic histocompatibility (Hh-1) phenotype and the regulation of its expression. AB - Hybrid resistance (HR) is primarily controlled by the genes of the Hemopoietic histocompatibility-1 (Hh-1) locus within the H-2 complex. HR is a consequence of the Hh-1-controlled target determinants in homozygous parental strain mice and their absence in heterozygous F1 hybrid mice. To examine the mechanism that controls the Hh-1 phenotype, three independent clones of somatic cell hybrids between parental lines EL-4 (C57BL/6 origin, H-2b) and R1 (C58 origin, H-2k) were studied. The line EL-4 is Hh-1b-positive and is subject to HR by H-2b heterozygous F1 mice, but R1 lacks the Hh-1b allele and is not susceptible to HR. Of the three hybrid clones, F263.2 is Hh-1b-positive, whereas the other two, F262.2 and F264.2, are Hh-1b-negative, as judged by these cells' capacity to compete in vivo with the grafted parental C57BL/6 bone marrow cells in the resistant (C57BL/6 x C3H)F1 mice. All three clones express the H-2b and H-2k class I antigens equally well, are susceptible to activated NK cells to the same extent, and all carry four copies of chromosome 17. However, Southern analysis reveals that clone F263.2 contains three copies of H-2b chromosome and one H-2k, whereas the other two clones carry two copies each of the parental chromosome 17. The results suggest that the relative copy number of specific alleles is the crucial determinant of the Hh-1 phenotype, and render unlikely both the gene dosage hypothesis and the trans-acting dominant suppression hypothesis to account for the noncodominant expression of the Hh-1 phenotype. PMID- 1735559 TI - Conservation of the promoter region of DRA-like genes from nonhuman primates. PMID- 1735560 TI - The recombination activating genes, RAG 1 and RAG 2, are on chromosome 11p in humans and chromosome 2p in mice. AB - The recombination activating genes RAG-1 and RAG-2 are adjacent genes that act synergistically to activate variable-diversity-joining (V(D)J) recombination. Southern analysis of hybrid cell lines derived from patients with the Wilms tumor aniridia-genitourinary defects-mental retardation (WAGR) syndrome and from mutagenized cell hybrids selected for deletions in chromosome 11 has allowed us to map the chromosomal location of the human RAG locus. The RAG locus defines a new interval of human chromosome 11p, but is not associated with any genetically mapped human disease. Guided by the chromosomal localization of the human recombination activating genes, we have also mapped the location of the mouse Rag locus. PMID- 1735561 TI - Reactivity of small blood vessels in hypertension: relation with structural changes. State of the art lecture. AB - Small blood vessels, particularly small arteries of 150-300 microns in lumen diameter and larger arterioles of 50-150 microns in lumen diameter, are the most important location of the arterial bed that undergoes changes resulting in the increased peripheral resistance that characterizes elevated blood pressure. This article reviews these morphological and functional alterations of small blood vessels. Study of mesenteric small arteries with a lumen diameter of 220-260 microns revealed consistently a reduced external and lumen diameter in renal and deoxycorticosterone acetate-salt hypertensive rats early in the evolution of hypertension. The media of the vessel wall was significantly thickened in the hypertensive rats, and the media/lumen ratio was increased. Although the tension that developed in response to different vasoconstrictors was not elevated or was even decreased in hypertensive rats, exaggerated transmural pressures resulted in the isolated blood vessels as a consequence of the law of Laplace because of the narrowed lumen. Similar findings were obtained in small resistance arteries from subcutaneous gluteal biopsies of hypertensive humans. In arterioles, on the other hand, decreases in the density of blood vessels (rarefaction) and in vasomotion amplitude may play a more important role than reductions in lumen diameter. As a consequence of the design of small resistance blood vessels and as a result of functional and structural alterations, which may be primary to or a consequence of high blood pressure, the pressor effect of vasoconstrictors is amplified and interacts with other factors to contribute to the maintenance of elevated blood pressure even if the intrinsic response of vascular smooth muscle to these agents is not exaggerated. PMID- 1735562 TI - Localization of components of the kallikrein-kinin system in the kidney: relation to renal function. State of the art lecture. PMID- 1735563 TI - Insulin enhances pressor responses to norepinephrine in rat mesenteric vasculature. AB - Hyperinsulinemia and insulin resistance have been proposed to play a role in human and experimental hypertension. To characterize this relation further, we examined the pressor responses to periarterial nerve stimulation (PNS) and norepinephrine infusion in the isolated mesenteric vasculature of the normal rat before and after insulin (10, 100, and 1,000 microunits/ml) infusion. The pressor responses to PNS were similar before and after insulin, except at the highest dose of insulin (1,000 microunits/ml) and the highest frequency of PNS (10 Hz). However, insulin significantly increased the pressor responses to norepinephrine. This increase in responsiveness was evident at all doses of insulin studied. In contrast, insulin did not affect the pressor responses to either angiotension II or serotonin administration. The mechanism or mechanisms for the augmented pressor response to norepinephrine after insulin infusion remain to be determined. However, the selectivity of the response for norepinephrine and the absence of a marked pressor increase after PNS indicate that the mechanism probably involves either the alpha-receptor itself or an amplification of the postreceptor signal transduction. The role of chronic hyperinsulinemia and insulin resistance in the pathogenesis of essential hypertension requires further study. PMID- 1735564 TI - Chemical renal medullectomy and arterial pressure response to sinoaortic denervation. AB - We investigated in conscious Wistar-Kyoto rats the effect of chemical renal medullectomy on the responses of mean arterial pressure, arterial pressure lability, and heart rate to sinoaortic deafferentation (SAD). Chemical medullectomy was obtained by the intravenous administration of 2-bromoethylamine hydrobromide (2-BEA) 2-3 weeks before SAD or sham SAD. Chemically medullectomized rats were compared with control rats treated with saline. In control rats, the increase in mean arterial pressure elicited by SAD was not significantly greater than that produced by sham SAD. In medullectomized rats, SAD significantly increased mean arterial pressure compared with sham SAD. No direct relation was observed between the response of mean arterial pressure to SAD and the grade (1, 2, or 3) of lesion of the renal papilla. In control rats, SAD increased significantly arterial pressure lability. Chemical medullectomy did not affect basal lability or the increased lability after SAD. No direct relation was observed between increased arterial pressure lability due to SAD and the grade of lesion of the renal papilla. SAD produced a conspicuous tachycardia in control rats. Chemical medullectomy did not affect basal heart rate or the tachycardia produced by SAD. No direct relation was observed between the extent of this tachycardia and the grade of lesion of the renal papilla. These data indicate that lesions of the renal papilla lead to a significant increase in mean arterial pressure after SAD, without affecting basal pressure or heart rate. In addition, SAD per se did not increase significantly the mean arterial pressure in control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735565 TI - Actions of cromakalim in isolated human saphenous vein. AB - The present study was performed to evaluate the effect of cromakalim on human vein in vitro. Branches of human saphenous vein (leftovers), obtained from patients undergoing heart revascularization surgery, were cut into rings and suspended in an organ chamber filled with Krebs-Ringer solution for the measurement of isometric contractile force. Concentration-response curves to norepinephrine and serotonin were constructed before and after pretreatment with cromakalim. The concentration-response curves to norepinephrine and serotonin were displaced to the right, and the maximal responses to both agonists were significantly inhibited by cromakalim in a concentration-dependent manner. Following sustained contraction induced by prostaglandin F2 alpha or 20 mM KCl, the cumulative addition of cromakalim to the organ chamber produced a concentration-dependent relaxation. However, in veins precontracted with 60 mM KCl the addition of cromakalim in concentrations of up to 10(-5) M did not induce relaxation. The relaxation induced by cromakalim in veins precontracted with prostaglandin F2 alpha was significantly inhibited by glibenclamide. These results indicate that cromakalim has a dilator effect in human vein that may play a helpful role in the treatment of angina. The venodilator effect of cromakalim in human saphenous vein probably involves activation of adenosine triphosphate regulated potassium channels. PMID- 1735566 TI - Effectiveness of atenolol in the treatment of hypertension during pregnancy. AB - This study assessed the effectiveness of atenolol in the treatment of moderate and severe hypertension during pregnancy. Seventy patients (mean age, 30.3 +/- 6.0 years), 35.7% primiparous, were included. Three groups were formed according to Davey and MacGillivray's classification: 1) chronic hypertension without proteinuria (12 patients), 2) gestational hypertension without proteinuria (52 patients), and 3) preeclampsia (six patients). Treatment with atenolol was started when blood pressure was 150/100 mm Hg or higher after 48 hours' rest. The treatment lasted at least 1 week; follow-up was every 2 weeks up to week 36, and from then on, weekly up to delivery. If blood pressure exceeded 160/110 mm Hg and the fetus was not yet mature, a second drug was added. A significant decrease in blood pressure was observed in the three groups (group 1: 155.8 +/- 15.0/100.8 +/ 7.6 versus 135.0 +/- 12.9/85.0 +/- 6.7 mm Hg; group 2: 154.2 +/- 13.6/104.9 +/- 9.3 versus 129.6 +/- 10.2/83.7 +/- 9.1 mm Hg; group 3: 158.3 +/- 27.1/104.1 +/- 8.0 versus 129.1 +/- 6.6/87.5 +/- 6.1 mm Hg). The doses of atenolol were 62.5 +/- 23.0 mg/day in group 1, 70.0 +/- 30.0 mg/day in group 2, and 100.0 +/- 41.0 mg/day in group 3. There was no fetal mortality. No significant difference occurred in newborn body weights. Four babies from group 2 mothers had an Apgar score of less than 7 at 1 minute, but only one remained abnormal after 5 minutes. In the same group, three cases of respiratory distress were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735567 TI - Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose finding pilot study. AB - The antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache). PMID- 1735568 TI - Renal effects of angiotensin II inhibition during increases in renal venous pressure. AB - Increases in renal venous pressure have been shown to consistently increase renal interstitial pressure; however, not until renal interstitial pressure is increased threefold is a natriuresis noted in normal animals. Since the intrarenal angiotensin II (Ang II) concentration has been postulated to increase with increasing renal venous pressure, the antinatriuretic action of Ang II could override the natriuretic effect of increased renal interstitial pressure. Therefore, the role of Ang II in the natriuretic response to increased renal venous pressure was examined in 10 pentobarbital-anesthetized dogs. Mean arterial pressure, renal blood flow, renal interstitial pressure, glomerular filtration rate, urinary sodium excretion, plasma renin activity, and prostaglandin E2 excretion were measured at renal venous pressures of 3, 15, and 30 mm Hg. The measurements were repeated after the administration of captopril (1 mg/kg i.v. bolus, n = 5) or [Sar1,Ile8]Ang II (50 micrograms/kg i.v. bolus + 50 micrograms/kg/hr infusion, n = 5). Under control conditions, mean arterial pressure, renal blood flow, plasma renin activity, and prostaglandin E2 excretion remained unchanged when renal venous pressure was increased. The elevations in renal venous pressure increased renal interstitial pressure from 7 +/- 2 to 12 +/ 2 and 22 +/- 4 mm Hg, while sodium excretion remained unchanged until renal venous pressure was 30 mm Hg. In the captopril-treated group, increasing renal venous pressure increased renal interstitial pressure as under control conditions; however, sodium excretion (23 +/- 4, 19 +/- 4, and 27 +/- 6 mueq/min) was not significantly increased even at the highest renal venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735569 TI - Changes in vascular resistance during carotid occlusion in normal and baroreceptor-denervated rats. AB - In the present study, we investigated changes in mesenteric, renal, and hindquarter vascular resistance during the pressor response produced by bilateral carotid occlusion (BCO) in conscious, freely moving normal and denervated (aortic, carotid, or both) rats. BCO was performed using special previously implanted cuffs. In control normal rats, the increase in mean arterial pressure (MAP) during early and late responses (37 +/- 4 and 21 +/- 2 mm Hg, respectively) was related to increased renal (125 +/- 12% and 45 +/- 10%) and mesenteric (38 +/ 13% and 41 +/- 5%) but not hindquarter (14 +/- 4% and 8 +/- 7%) vascular resistance. In aortic-denervated rats, the greater MAP increase in early and late responses (57 +/- 4 and 44 +/- 4 mm Hg, respectively) compared with normal rats was related to a marked increase in hindquarter (137 +/- 26% and 106 +/- 26%) and mesenteric (104 +/- 14% and 66 +/- 9%) vascular resistance. In carotid-denervated rats, MAP increase and change in vascular resistance were similar to those values observed in control rats. Sinoaortic-denervated rats showed a greater MAP increase (34 +/- 4 mm Hg) during late response and a reduced increase in renal vascular resistance (46 +/- 6%) during early response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735570 TI - Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats. AB - We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +/- 7 versus 173 +/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +/- 6 versus 167 +/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +/ 13 beats per minute) but a tachycardia in sham rats (+33 +/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats. PMID- 1735571 TI - Baroreceptor reflex control of heart rate during development of coarctation hypertension. AB - To study whether resetting of the baroreceptors is accompanied by normal reflex activity to the heart, we analyzed time-course changes of pressure, heart rate, baroreceptor reflex sensitivity, and plasma renin activity during the development of coarctation hypertension. Baseline heart rate was measured daily, and plasma renin activity and reflex changes in heart rate (bolus injections of either phenylephrine or nitroprusside, 0.2-25.6 micrograms/kg i.v.) were recorded at different times in coarcted and sham-coarcted rats. Hypertension was stable (approximately 39% from baseline mean arterial pressure of 112 +/- 3 mm Hg), whereas heart rate (333 +/- 4 beats per minute) showed a biphasic behavior: bradycardia at 6 hours (264 +/- 7 beats per minute) and tachycardia at 5 days (418 +/- 14 beats per minute). On day 10 of hypertension, heart rate was normal. Plasma renin activity was markedly increased only after 6 hours (4.9 times). Reflex bradycardia exhibited a progressive impairment: The slopes of the regression lines between changes in heart rate and changes in mean arterial pressure were not significantly reduced at 6 and 48 hours when the resetting was in development (changes of 17% and 28% from a control of -1.89 +/- 0.20 beats per minute/mm Hg) but were significantly depressed after the resetting had been completed (-51% and -56% at 5 and 10 days, respectively). Reflex tachycardia was significantly reduced in all periods studied (75%, 78%, 52%, and 61% at 6 hours and 2, 5, and 10 days, respectively; -3.92 +/- 0.42 beats per minute/mm Hg in sham rats).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735572 TI - Pressure-induced constriction of the afferent arteriole of spontaneously hypertensive rats. AB - In uncomplicated essential hypertension, renal blood flow, glomerular filtration rate, and glomerular capillary pressure are within the normal range despite elevated renal perfusion pressure, suggesting abnormally high resistance of the preglomerular vessels. Among various preglomerular vascular segments, the afferent arteriole (Af-Art) is thought to be the site responsible for most resistance. However, little is known about the vascular reactivity of the Af-Art or its alteration in hypertension. In this study, we tested the hypothesis that pressure-induced constriction is exaggerated in Af-Arts from spontaneously hypertensive rats (SHRs). Single Af-Arts were microdissected from kidneys of SHRs and normotensive control Wistar-Kyoto (WKY) rats and were microperfused in vitro. When pressure in the Af-Art was increased stepwise from 20 to 80 mm Hg, luminal diameter increased similarly in both WKY and SHR Af-Arts (from 10.0 +/- 0.8 to 18.6 +/- 1.3 microns and from 10.1 +/- 1.2 to 16.9 +/- 1.5 microns, respectively). However, when pressure was further increased to 140 mm Hg, the diameter remained unchanged in WKY Af-Arts (19.2 +/- 1.9 microns), whereas it decreased significantly to 11.1 +/- 0.9 microns in those from SHRs. We conclude that pressure-induced constriction is exaggerated in SHR Af-Arts, which may contribute to the development and maintenance of hypertension. PMID- 1735573 TI - Expression of alpha-smooth muscle actin in the developing kidney vasculature. AB - To determine whether alpha-smooth muscle (alpha-SM) isoactin is expressed in the maturing kidney as well as the changes associated with maturation, we processed for immunocytochemistry kidney sections from Wistar-Kyoto rats at various prenatal (15, 17, 19, and 20 days) and postnatal (2, 5, 10, 15, and 90 days) ages using a monoclonal anti-alpha-SM actin antibody. At 15 days of gestation, only a few mesenchymal cells contained alpha-SM actin. However, other fetal vasculature structures (heart, aorta, peripheral blood vessels) expressed alpha-SM actin. Vascular localization was first observed at 17 days of gestation in larger corticomedullary vessels. As maturation progressed, actin expression accompanied the outward growth and branching of the kidney vasculature. During fetal life (17 days), alpha-SM actin also was expressed within juxtamedullary glomeruli. As the centrifugal maturation of nephrons proceeded, intraglomerular expression extended to outer cortical glomeruli. After 10 days of postnatal life, once glomerular development was completed, intraglomerular expression was no longer present. Peritubular capillaries expressed alpha-SM actin during early (fetal and neonatal) development, but not in the adult kidney. We conclude that 1) expression of alpha-SM actin in the developing kidney is delayed with respect to other vascular beds, 2) expression of alpha-SM actin follows the centrifugal pattern of nephrovascular development, and 3) glomerular and peritubular capillary expression of alpha-SM actin is a transient developmental phenomenon associated with active glomerulogenesis and capillary growth. PMID- 1735574 TI - Renal denervation normalizes pressure and baroreceptor reflex in high renin hypertension in conscious rats. AB - High renin hypertension is usually accompanied by impairment of the baroreceptor reflexes. This feature has been mostly ascribed to overactivity of the renin angiotensin system. However, renal nerves could also modulate the baroreceptor reflexes. In the present experiments, the effect of renal denervation on the depressed baroreceptor reflexes was studied in rats subjected to aortic ligation between the renal arteries. Renal denervation of the ischemic kidney was performed at the same time as aortic ligation. The resulting effects on arterial pressure, heart rate, plasma renin activity, and baroreceptor reflex control of heart rate were studied 10-12 days after ligation and denervation. Aortic ligation induced high levels of mean arterial pressure (166 +/- 6 versus 110 +/- 3 mm Hg in controls), heart rate (380 +/- 9 versus 352 +/- 8 beats per minute in controls), and plasma renin activity (44 +/- 5 versus 6 +/- 1.2 ng angiotensin I/ml/hr). The baroreceptor reflex sensitivity for bradycardia and tachycardia was significantly reduced (-0.18 +/- 0.04 and -0.18 +/- 0.05, respectively, versus 2.3 +/- 0.01 and -2.4 +2- 0.1 beats per minute per mm Hg in controls). Denervation of the ischemic kidney attenuated the development of hypertension in aortic-ligated rats (122 +/- 3 mm Hg), lowering heart rate (319 +/- 8 beats per minute) and normalizing baroreceptor reflex sensitivity to bradycardia (-2.0 +/- 0.2 beats per minute per mm Hg) and to tachycardia (-4.0 +/- 0.1 beats per minute per mm Hg). Plasma renin activity was also normalized (4.3 +/- 2.4 ng angiotensin I/ml/hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735575 TI - Centrally infused bradykinin increases baroreceptor reflex sensitivity. AB - Kinins are present in the central nervous system, and central administration of bradykinin increases blood pressure and heart rate. In this study, we determined the effect of intracerebroventricular infusion of bradykinin on the baroreceptor reflex of conscious rats. Male Wistar rats were anesthetized with thiobarbital (40 mg/kg i.p.), and chronic intracerebroventricular cannulas (25 gauge) were implanted into the lateral ventricles. Baroreceptor control of heart rate was evaluated by recording reflex heart rate changes (beats per minute) in response to mean arterial pressure changes (mm Hg) produced by bolus injection of phenylephrine (0.5-20 micrograms/kg i.v.) or sodium nitroprusside (0.5-25 micrograms/kg i.v.). The ratio beats per minute/mm Hg or the mean slope of the individual regression lines of the relation between heart rate and mean arterial pressure changes for increases or decreases in arterial pressure was used as an index of baroreceptor reflex sensitivity. Baroreceptor control of heart rate was evaluated within 1 and 3 hours of intracerebroventricular infusion of bradykinin (7.5 micrograms/7 microliters/hr) or saline (7 microliters/hr). There was no change in basal mean arterial pressure or heart rate during central bradykinin infusion (112 +/- 2 mm Hg and 402 +/- 18 beats per minute in the control period). After 1 hour of central bradykinin infusion, there was a significant increase of baroreceptor reflex sensitivity for increments in mean arterial pressure (-2.91 +/- 0.26 versus -1.5 +/- 0.24 beats per minute/mm Hg in the control period; p less than 0.01, paired Student's t test). In contrast, no significant changes were observed for the reflex tachycardia. Similar results were obtained with 3 hours of infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735576 TI - Effect of selective denervation of baroreceptors on pulmonary ventilation and arterial pressure lability in rat. AB - Earlier studies report that sinoaortic baroreceptor denervation (SAD) in rats causes moderate elevation of mean arterial pressure along with a marked increase of arterial pressure lability (APL). In this context, we studied the effects of selective aortic denervation (AD) or selective carotid denervation (CD) on the regulation of blood pressure. In addition, we evaluated the effects of selective or total baroreceptor denervation on pulmonary ventilation and ventilation related changes of arterial pressure. Mean arterial pressure was evaluated by computer-assisted techniques, and ventilation was measured by whole body plethysmography on conscious freely moving rats. With this approach, equal increases of mean arterial pressure were obtained for rats that had undergone AD, CD, and SAD. The APL was higher in SAD rats than in selectively denervated rats. CD and AD rats had an elevated APL relative to sham-operated animals, and its increase was approximately equal for the two selectively denervated groups. Total as well as selective denervation had relatively small effects on ventilation and on the general pattern of breathing. In all groups, this pattern consisted of regular ventilation, periodically interrupted by single deeper breaths. In SAD, AD, and CD animals, these larger tidal volumes were associated with marked transient reductions of mean arterial pressure, whereas small decreases of pressure occurred in sham-operated rats. The results indicate that both groups of baroreceptors must be present to keep mean arterial pressure at its normal level. Moreover, both receptor groups are equally important in reducing APL. Ventilation contributes to generation of APL after total or selective baroreceptor removal. Such ventilation-induced pressure changes are kept at a minimum in baroreceptor intact rats. PMID- 1735577 TI - Identification of cardiovascular neurons in the rostral ventromedial medulla in anesthetized rats. AB - Recent studies have identified a region in the rostral ventromedial medulla (RVMM) of rats that appears to be involved in cardiovascular function. Since these studies used either microinjection of lidocaine or electrical stimulation, the exact contribution of intrinsic neurons as opposed to fibers of passage could not be determined. The present study was performed to map the location of neurons in RVMM from which changes in mean arterial pressure could be elicited by the microinjection of the excitatory amino acid analogue N-methyl-D-aspartic acid (NMDA) (20 ng/50 nl), which selectively activates cell bodies in barbiturate anesthetized rats. Microinjection of NMDA into RVMM most often (53%) elicited pressor responses (31 +/- 7 mm Hg). On the basis of these responses, RVMM was determined to encompass a large portion of the nucleus gigantocellularis 0.5-1.5 mm lateral to the midline, 0.5-3.5 mm above the ventral surface, and extending from the rostral to the caudal pole of the facial nucleus. Depressor responses ( 21 +/- 3 mm Hg) were found at all levels of RVMM but were most concentrated and of the largest magnitude in the rostral and caudal poles of RVMM. Microinjection of the inhibitory neurotransmitter glycine (500 mM) was used to determine whether neurons in RVMM were contributing to the maintenance of arterial pressure. Microinjection of glycine decreased arterial pressure (-15 +/- 2 mm Hg) throughout most of RVMM. Unexpectedly, increases in mean arterial pressure (24 +/ 3 mm Hg) were elicited by microinjection of glycine into the same region in RVMM in which NMDA most frequently elicited pressor responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735578 TI - Early depression of the baroreceptor sensitivity during onset of hypertension. AB - We studied the correlation of changes in gain sensitivity of the baroreceptors and the development of resetting of the baroreceptors 2 and 6 days after the onset of hypertension produced by subdiaphragmatic aortic constriction in rats. Mean arterial pressure of anesthetized rats was maintained at approximately the same level as that of conscious rats, and baroreceptor function curves were studied on a beat-to-beat basis by computer. After 2 days of hypertension, the difference between the systolic pressure threshold and the control diastolic pressure was -13 +/- 2 mm Hg (125 +/- 3 versus 138 +/- 4 mm Hg). Individual values showed that in seven of nine hypertensive rats, the difference was less than 15 mm Hg, indicating complete resetting. After 6 days of hypertension, all rats exhibited complete resetting, when the systolic pressure threshold was similar to control diastolic pressure (143 +/- 4 versus 141 +/- 2 mm Hg), indicating that more than 2 days of hypertension is necessary for full displacement of the pressure thresholds when all hypertensive rats are considered. Slopes of the baroreceptor curves after 2 and 6 days of hypertension showed that baroreceptor gain was depressed by 25% and 34%, respectively. The difference was not statistically significant (1.07 +/- 0.054% versus 0.94 +/- 0.049% and 1.43 +/- 0.075% in controls). When changes in pressure were circumscribed to a more physiological range, a depression of 25% in response to +10 mm Hg and 37% in response to -10 mm Hg was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735579 TI - Rapid eye movement sleep deprivation and hypertension. Genetic influence. AB - We studied the importance of genetic predisposition in the development of stress induced hypertension in the spontaneously hypertensive rat (SHR), Wistar-Kyoto (WKY) rat, and borderline hypertensive rat (BHR; first-generation offspring of SHR and WKY). Rats were submitted to seven 72-hour sessions of rapid eye movement sleep deprivation (REM-sd) every other week during 13 weeks. Tail arterial pressure was determined throughout the experiment. At the end of the study, mean arterial pressure (direct measurement), sympathetic activity (acute blockade with propranolol and phentolamine), and ventricular weight were determined. Results showed that REM-sd induced sustained hypertension only in rats with a partial predisposition to developing hypertension (BHRs). Values of tail arterial pressure at the end of the study were BHR REM-sd, 175 +/- 1.6 mm Hg and control BHR, 155.9 +/- 0.9 mm Hg, p less than 0.05; SHR REM-sd, 219 +/- 2.6 mm Hg and control SHR, 211.9 +/- 3.4 mm Hg, NS; WKY REM-sd, 123.9 +/- 2 mm Hg and control WKY, 125.4 +/- 2.2 mm Hg, NS. Stressed groups showed higher reduction of mean arterial pressure than their controls when submitted to sympathetic blockade (SHR REM-sd, -75.7 +/- 13.2 mm Hg and control SHR, -60 +/- 4.5 mm Hg, p less than 0.05; BHR REM-sd, -38.4 +/- 3.6 mm Hg and control BHR, -24.3 +/- 2.1 mm Hg, NS; WKY REM-sd, -34.4 +/- 2.5 mm Hg and control WKY, -25.6 +/- 3.3 mm Hg, NS). REM-sd increased ventricular weight in all strains. These increments showed no correlation with blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735580 TI - Doppler ultrasonography for the detection of renal artery stenosis in transplanted kidneys. AB - The objective of this study was to evaluate the importance of Doppler ultrasonography in diagnosing renal artery stenosis in transplanted kidneys using angiography as the accepted gold standard. Fourteen kidney graft recipients with clinical severe hypertension, impaired renal function, or both had their renal artery blood flow studied by Doppler ultrasonography before angiography. Seven patients had renal artery stenosis diagnosed by angiography. In six of them, the same diagnosis was achieved by Doppler ultrasonography, and in one patient, Doppler ultrasonography and angiography showed total occlusion of the renal artery. In six patients, both exams were normal. The only false-negative result was in an 8-year-old patient whose graft was placed in the left flank. The Doppler ultrasonography specificity was 100% and its sensitivity was 87.5%. The predictive value of a positive test was 100%; the predictive value of a negative test was 85.7%. Doppler ultrasonography of the renal artery in transplanted kidneys showed an accuracy of 92.86% in diagnosing renal artery stenosis. Because the technique is noninvasive, it should be considered as a first-line screening test. PMID- 1735581 TI - Ventricular function by radionuclide ventriculography in malignant hypertension. AB - Malignant hypertension is a unique and natural model for the study of abnormalities of left ventricular function due to arterial hypertension, because the development and regression of these abnormalities can be observed in a short period. Studies of ventricular function by radionuclide ventriculography, either before or after therapy, have not been previously reported in malignant hypertensive patients. We used this methodology to study left ventricular function in 17 malignant/accelerated hypertensive patients at the time of admission to the hospital and 3, 6, and 9 months after discharge. Seventy percent of patients (12 of 17) had symptoms of congestive heart failure at admission. We compared these data with those obtained in 12 normotensive subjects and 13 mild to-moderate untreated hypertensive patients. Blood pressure of malignant hypertensive patients was 213 +/- 26/140 +/- 17 mm Hg at admission and 165 +/- 23/101 +/- 15 after 9 months of therapy. Radionuclide ventriculography at admission showed that peak filling rates of malignant hypertensive patients (2.13 +/- 0.21 end-diastolic volume [counts] [EDV]/sec) were significantly lower than those in normotensive subjects (2.40 +/- 0.41) and in mild-to-moderate hypertensive patients (2.46 +/- 0.21). In contrast, peak ejection rates were significantly higher in malignant hypertensive patients (3.44 +/- 0.38 EDV/sec) than in the two control groups (3.01 +/- 0.32 and 3.10 +/- 0.43, respectively). Ejection fractions were similar in the three groups of patients. After 9 months of therapy, peak filling rates of malignant hypertensive patients increased to 2.38 +/- 0.35 EDV/sec, whereas peak ejection rates decreased to 2.89 +/- 0.43 EDV/sec, both not significantly different from data in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735582 TI - Familial aggregation of arterial blood pressure and possible genetic influence. AB - The aggregation of arterial blood pressure, weight, and height were compared between family members of children and adolescents with blood pressure percentiles at or above 95 (group 1) and at or below 50 (group 2). Weight, height, and systolic and diastolic blood pressures were significantly higher in siblings and target individuals of group 1 (p less than 0.001). Weight and systolic and diastolic blood pressures were significantly higher in mothers of group 1 (p less than 0.001). Covariant analysis comparing the average systolic and diastolic blood pressures of both groups controlled by age, age and weight, and age and Quetelet index revealed that the arterial blood pressure of mothers, siblings, and target individuals remained higher in group 1 (p less than 0.05 to p less than 0.001). These observations show a strong familial aggregation of arterial blood pressure not dependent only on physical development and also raise the question of a genetic basis as a possible mechanism of systemic arterial hypertension. PMID- 1735583 TI - Vascular reactivity in young adults and cardiovascular disease. A prospective study. AB - Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease. PMID- 1735584 TI - The effect of upright tilt on nifedipine-induced natriuresis. AB - Calcium channel blockers are antihypertensive agents with diuretic actions. Yet edema occurs in some patients receiving long-term treatment with these drugs. As with other vasodilators, stimulation for fluid retention could result from systemic vasodilation. We speculated that the upright posture could enhance sodium retention. To test this hypothesis, we studied the effect of upright tilt in 10 patients before and after the oral administration of 20 mg nifedipine. Before nifedipine upright tilt caused a 41% drop in the sodium excretion rate, from 0.27 +/- 0.04 to 0.16 +/- 0.03 meq/min (p less than 0.05). Fractional sodium excretion decreased by 46%, from 2.4 +/- 0.5 to 1.3 +/- 0.3% (p less than 0.01). Urinary volume and renal plasma flow also decreased (p less than 0.05). Plasma renin activity (PRA) rose by 46% (p less than 0.005). With the patients in the supine posture nifedipine increased the sodium excretion rate to 0.49 +/- 0.09 meq/min (p less than 0.05). Fractional sodium excretion was 3.1 +/- 0.6 meq/min (p = 0.2). The natriuresis took place despite a fall in mean blood pressure and a significant rise in PRA (up 115% from prenifedipine supine values, p less than 0.005). Renal plasma flow also increased (p less than 0.01). The upright tilt caused a reversal of the nifedipine-induced natriuresis. The sodium excretion rate dropped to 0.23 +/- 0.05 meq/min and fractional sodium excretion to 1.3 +/- 0.2% (both not different from control). This drop in natriuresis occurred while mean blood pressure was at its lowest and PRA was 254% above the initial levels (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735585 TI - Endothelium-dependent and endothelium-independent effects of adenosine diphosphate in renovascular hypertension. AB - Norepinephrine-induced responses in isolated perfused mesenteric vascular bed from normotensive and renovascular hypertensive rats were examined in the presence of adenosine diphosphate (ADP, 2 x 10(-6) M). Responses to norepinephrine were significantly greater in vessels from hypertensive rats. Norepinephrine-induced contractions increased after the removal of endothelium. N omega-Nitro-L-arginine (L-NOARG), a potent inhibitor of nitric oxide formation, similarly increased contractions. The greatest responses were obtained, however, after treatment of the vascular segments with methylene blue. The presence of ADP caused significant endothelium-dependent decreases in contractions. Although decreases caused by ADP in vessels with endothelium after treatment with L-NOARG were not statistically significant, a tendency to decreased responses seems to suggest that L-NOARG diminishes but does not completely prevent the effect of ADP in mesenteric vessels. Methylene blue partially reduced the endothelium-dependent ADP-induced relaxant effects in sham-operated nephrectomized rats. A tendency to increased contractions to norepinephrine was observed in the presence of ADP after removal of endothelium. Thus, in the mesenteric resistance arteries of the rat under stimulation by ADP, it appears that nitric oxide released from L arginine and the activity of soluble guanylate cyclase account only in part for the endothelium-dependent decreased responses to norepinephrine. When nitric oxide formation or soluble guanylate cyclase activity are depressed simultaneously with endothelium damage, ADP released from platelets or red blood cells may be an important factor that acts synergically with vasoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735586 TI - Angiotensin converting enzyme inhibitors versus calcium antagonists in the treatment of diabetic hypertensive patients. AB - Angiotensin converting enzyme inhibitors and calcium antagonists are effective agents for controlling high blood pressure in diabetic patients. We selected 30 type II diabetic patients with proteinuria and evaluated the effect of these drugs on renal function and proteinuria. In a double-blind trial, patients received either 40 mg/day enalapril or 40 mg/day nifedipine during 12 months. They also received a hypoproteic diet with 0.8 g/kg wt/day of protein. In the enalapril group (10 men and eight women), mean arterial blood pressure was 112.0 +/- 12 mm Hg, creatinine clearance was 58.6 +/- 12.4 ml/min, and 24-hour proteinuria was 4.36 +/- 3.23 g/24 hr before treatment. After treatment, mean arterial blood pressure was 82.0 +/- 8.30 mm Hg (p less than 0.001), creatinine clearance was 66.6 +/- 13.8 ml/min (NS), and 24-hour proteinuria was 0.56 +/- 0.78 g/24 hr (p less than 0.001). In the nifedipine group (six men and six women), mean arterial blood pressure was 114.0 +/- 8.0 mm Hg, creatinine clearance was 67.8 +/- 19.6 ml/min, and 24-hour proteinuria was 2.84 +/- 1.31 g/24 hr before treatment. After treatment, mean arterial blood pressure was 86.0 +/- 7.0 mm Hg (p less than 0.001), creatinine clearance was 51.4 +/- 7.9 ml/min (p less than 0.001), and 24-hour proteinuria was 2.66 +/- 0.89 g/24 hr (NS). These results show a similar hypotensive action and different renal effects between these two drugs after 12 months of treatment. PMID- 1735587 TI - Effect of bradykinin on isolated mesenteric arteries of the rat. AB - Bradykinin is a potent vasodilator peptide; however, its half-life in vivo is very short because of various plasma and tissue peptidases that hydrolyze bradykinin to inactive fragments. We studied the role of kininase II (angiotensin converting enzyme) and neutral endopeptidase 24.11 (enkephalinase) in the catabolism of bradykinin in vascular tissue by determining the effect of inhibitors of kininase II (captopril) and of endopeptidase 24.11 (phosphoramidon) on the action of bradykinin on rat isolated mesenteric arteries. Because bradykinin may induce prostaglandin formation and release, we also studied the effect of a cyclooxygenase inhibitor, indomethacin, on the action of bradykinin. The mesenteric bed was isolated from rats (250-300 g) with rats under either anesthesia and was perfused with Krebs' solution (4 ml/min) containing phenylephrine (0.5-1.0 microgram/ml) to produce a mean perfusion pressure of 120 130 mm Hg. Bradykinin (2.5-40.0 ng), injected as a bolus, produced a dose dependent decrease in perfusion pressure. In the presence of indomethacin (1.0 microgram/ml), the amplitude of the vasodilator responses to bradykinin was not significantly affected, although the duration of the responses was increased approximately two to four times. In the presence of captopril (1.0 microgram/ml), bradykinin elicited either a vasodilator or a biphasic effect. The vasodilator effect was greatly potentiated by captopril, whereas the duration of the response was unchanged when compared with control experiments. When present, the pressor responses were also dose related. In the presence of indomethacin plus captopril, bradykinin produced only a fall in perfusion pressure that lasted five to six times longer than without any treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735588 TI - Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats. AB - We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with NG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n = 8), mean blood pressure increased by 16.2 +/- 2.6 mm Hg, and heart rate decreased by 54.3 +/- 16.7 beats per minute. In comparison with rats injected with 5% dextrose (n = 14), cardiac index was lower by 35.6% (p less than 0.01), and total peripheral vascular resistance was higher by 51.6% (p less than 0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (p less than 0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 micrograms/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2% (p less than 0.01) and vascular resistance increasing by 75.3% (p less than 0.01) compared with changes produced by LNMMA alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735589 TI - Hypokalemia, glucose intolerance, and hyperinsulinemia during diuretic therapy. AB - Hypokalemia and glucose intolerance may result from diuretic therapy. Increases in plasma insulin and glucose levels have been observed in thiazide-treated hypertensive patients and have been attributed to a diminished insulin sensitivity induced by diuretic therapy. To investigate the effects of hypokalemia on glucose tolerance and insulin secretion, we studied 21 essential and nine diabetic hypertensive patients after 4 weeks of placebo and after 4 weeks of chlorthalidone therapy (25 mg/day). Plasma glucose and insulin levels were measured for a 3-hour period after a 75-g glucose oral dose. Hypokalemia developed in seven of the essential hypertensive patients (HK group), whereas only one diabetic patient had decreased plasma potassium levels to below 3.5 meq/l. The results obtained in the HK group after chlorthalidone showed that plasma glucose and insulin values increased after the oral glucose load to levels significantly higher than those observed after placebo. In contrast, the patient who remained normokalemic after chlorthalidone did not show any change in plasma insulin and glucose levels during glucose tolerance testing. These results show that diuretic therapy may induce hyperglycemia and hyperinsulinemia and suggest that potassium depletion is involved in the increase in insulin resistance that has been demonstrated during thiazide therapy. PMID- 1735590 TI - Submandibular enzymatic vasoconstrictor messenger RNA in rat kidney. AB - Recently, we reported the isolation and identification of a potent vasoconstrictor enzyme from the rat submandibular gland, a member of the rat kallikrein gene family, which we named submandibular enzymatic vasoconstrictor (SEV). We studied whether messenger RNA (mRNA) for SEV is present in the kidney and isolated glomeruli, using the polymerase chain reaction assay with primers specific to the entire rat kallikrein family that would amplify a 430-bp fragment from their mRNA. As a probe we used a phosphorus-32-labeled oligonucleotide specific for SEV mRNA. A fragment of the predicted size was obtained on Southern blot for amplified renal RNA; however, no signal was obtained with glomerular RNA. To further confirm the presence of SEV mRNA in the kidney, polymerase chain reaction was repeated using primers specific to SEV mRNA that would amplify a 372 bp fragment from SEV mRNA alone. Again, a fragment of the predicted size was obtained on Southern blot after amplification of renal RNA but not RNA from the glomeruli. Southern blot of polymerase chain reaction-amplified RNA with primers that amplified the entire kallikrein gene family, using kallikrein complementary DNA that recognizes all members of the kallikrein gene family as a probe, revealed a 430-bp fragment for both renal and glomerular RNA, indicating that glomeruli contain mRNA for a member or members of the kallikrein family other than SEV. When the Southern blots were hybridized with a 32P-labeled oligonucleotide probe specific for glandular kallikrein, a fragment of the predicted size was obtained from amplified renal RNA but not glomerular RNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735591 TI - Bayesian analysis supports use of ambulatory blood pressure monitors for screening. AB - To assess whether there is a role for ambulatory blood pressure monitoring (ABPM) in screening for hypertension, we conducted Bayesian analysis of office blood pressure (OBP) as a diagnostic "test" in populations with different prior probabilities (PP) of hypertension. OBP was considered a positive test if systolic blood pressure was greater than 140 mm Hg or diastolic pressure was greater than 90 mm Hg. Chosen daytime ABPM cutoffs for a "gold standard" diagnosis of hypertension were systolic pressure of 139 and diastolic pressure of 88 mm Hg. Sensitivity and specificity of OBP were determined in 72 patients with established hypertension (PP = 1). After 3 weeks off therapy, OBP was 168 +/- 3/101 +/- 1 and ABPM was 151 +/- 2/94 +/- 1 mm Hg. Systolic ABPM was in the normotensive range in 17 patients and diastolic in 15 patients. OBP was falsely positive in 14 and 15 of these patients, respectively. Thus, sensitivity and specificity of OBP were 0.8909 and 0.1765 (systolic) and 0.9825 and 0 (diastolic). These data cannot be extrapolated to populations with lower PPs for use of Bayes' theorem. Hence, we calculated sensitivity and specificity for PP = 0 from published series of ABPM in normotensive subjects and used our measurements and these calculations in arithmetic interpolations for populations with PP 0.1-0.9. Sigmoid relations between PP and predictability of hypertension by a positive OBP were disclosed by use of Bayes' theorem. Their best-fit cubic polynomials predict that an elevated OBP will misdiagnose hypertension 46-50% of the time in a general population (PP = 0.2) but only 8-9% in a specialty practice (PP = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735592 TI - Blood pressure control in children of Cordoba, Argentina. AB - The aims of the present study were 1) to evaluate blood pressure (BP) and its distribution curve in a highly representative population of children and adolescents from Cordoba, Argentina, to determine the normal BP pattern, and 2) to establish the relation between other factors and BP levels. BP data recorded during the years 1984-1987 were evaluated in 280,584 children and adolescents aged 5-15 years (52.1% boys and 47.9% girls) corresponding to the nine sanitary districts of the province (urban, rural, mountain, and plains areas), which represent 75% of the children of the whole province. Recordings were carried out by trained physicians who used pediatric BP cuffs and calibrated sphygmomanometers. Korotkoff periods 1 and 5 were considered as the systolic and diastolic BP, respectively. BP was recorded in groups of three to five students with students in a sitting position as part of the routine physical examination and after a thorough explanation of the methodology. For statistical analysis, the Student's t test and stepwise regression analysis were used. Percentile tables and curves were prepared for each age and sex group. Weight and height values were added to the information obtained. Diastolic BP was greater in girls than in boys between the ages of 11 and 14. Systolic BP was lower and diastolic BP was higher in the US Task Force study compared with these findings. Of all the independent variables evaluated, weight influenced BP the most. Age had less influence on BP when height and weight were normalized by regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735593 TI - Severe hypertension induces disturbances of renal autoregulation. AB - To study if the severity of hypertension could be associated with disturbances of the autoregulation of renal blood flow and glomerular filtration, we compared the renal hemodynamic and functional responses to acute blood pressure reductions of a group of patients with moderate essential hypertension (n = 10) with those of a group of patients with severe hypertension (n = 10). Blood pressure was reduced to normal levels by a stepwise infusion of sodium nitroprusside, and effective renal blood flow (by 131I-hippuran), glomerular filtration rate (by endogenous creatinine clearance), and filtration fraction were determined. After acute blood pressure normalization, effective renal blood flow and glomerular filtration rate were significantly reduced in patients with severe hypertension (-41.6 +/- 8.3% and -44.7 +/- 6.8%, respectively; p less than 0.01 for both) but not in those with moderate hypertension (+4.9 +/- 9.1% and +6.2 +/- 13.3%, respectively; NS). Filtration fraction remained unchanged in both groups. These results show that severe but not moderate essential hypertensive patients have a displacement to the right of the lower limit of the renal autoregulation curve due to impaired vasodilation to maintain adequate renal blood flow during acute reductions of blood pressure. This impairment may be due to anatomic or functional defects of preglomerular vessels, or to both. Furthermore, the inability to maintain adequate glomerular filtration in these circumstances shows that patients with severe hypertension also have an impaired ability to adjust postglomerular vasomotor tone in the face of reductions in glomerular blood flow. PMID- 1735594 TI - Renin distribution in the rabbit renal microvasculature. AB - Immunocytochemical studies have shown that renin, which is normally located in the juxtaglomerular afferent arteriole, may also be found farther upstream toward the interlobular artery during chronic stimulation of the renin-angiotensin system. We assessed the renin distribution along the renal microvasculature using both quantitative analysis and immunocytochemistry in rabbits that received a normal sodium diet (0.48% NaCl), a low sodium diet (0.04% NaCl), or enalapril (1 mg/kg/day) for 4 weeks. From the outer cortex we microdissected 1) the proximal portion of the afferent arteriole (p-AF) extending from the interlobular artery to a point 50 microns from the glomerulus, 2) the distal 50 microns including its intact terminus (d-AF), and 3) the glomerulus without the vascular pole (GL) and measured their renin content. In controls, renin was 0.3 +/- 0.2, 27.0 +/- 5.2, and 2.8 +/- 0.5 ng angiotensin I/hr/arteriole (or GL) in the p-AF, d-AF, and GL, respectively. The low sodium diet and enalapril increased renin in the d-AF (53.1 +/- 6.9 and 68.4 +/- 8.1, respectively) but not in the GL (3.3 +/- 1.0 and 3.6 +/ 0.7). In the p-AF, both caused a small increase (delta = 1.5); however, this increase was minuscule compared with the large increase in the d-AF (delta = 41).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735595 TI - Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors. AB - Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10( 6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735596 TI - Possible role of the vascular renin-angiotensin system in hypertension and vascular hypertrophy. AB - To investigate the vascular renin-angiotensin system in two-kidney, one clip (2K1C) hypertension, we measured angiotensinogen messenger RNA (mRNA) in the aorta and aortic and plasma angiotensin II (Ang II) concentration in 2K1C rats during early (4 weeks) and chronic (16 weeks) phases. Four weeks after clipping, there was no significant change in aortic angiotensinogen mRNA in both groups. However, the levels of plasma and aortic Ang II in 2K1C rats were significantly elevated compared with levels in control rats (p less than 0.05). Sixteen weeks after clipping, aortic angiotensinogen mRNA in 2K1C rats did not differ compared with the level in control rats. The aortic Ang II level in 2K1C rats was significantly increased compared with that in control rats (p less than 0.05), whereas there was no significant difference in the plasma Ang II level between the groups during this chronic phase. During both phases, morphological studies in 2K1C rats showed arteriosclerotic changes, with a significant increase in the wall-to-lumen ratio (p less than 0.01). The present study is the first to demonstrate an increase in vascular Ang II levels and concomitant morphological arteriosclerotic changes during both the early and chronic phases in 2K1C rats. Together with the results of our previous study that demonstrated an elevation of vascular renin activity during the early phase and increased vascular angiotensin converting enzyme activity during the chronic phase, we conclude that the elevated vascular renin activity and vascular angiotensin converting enzyme activity during each phase may play a dominant role in the increase in vascular Ang II observed during both phases. PMID- 1735597 TI - Nonprostanoid endothelium-derived factors inhibit renin release. AB - Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735598 TI - Renin-angiotensin-aldosterone system in normal and hypertensive pregnancy. Response to postural stimuli. AB - Most studies that have attempted to distinguish pregnancy-induced hypertension from chronic hypertension in pregnancy include arbitrary clinical definitions and morphological reports based on renal biopsy. To evaluate whether these conditions have different responses to stimuli to the renin-angiotensin-aldosterone system, we studied four normal nonpregnant women, eight normal pregnant women, 10 women with pregnancy-induced hypertension, and 14 with chronic hypertension in pregnancy, in the third trimester of pregnancy, after they had sequentially adopted the supine, the left lateral recumbent, and the orthostatic positions for 90 minutes each. Postural maneuvers did not significantly change mean arterial pressure in pregnancy-induced hypertensive or in normal pregnant women, although in chronic hypertensive women, a significant reduction in this parameter was observed in left lateral recumbency. The renin-angiotensin-aldosterone system was significantly less activated with women in the supine position in pregnancy induced hypertensive and chronic hypertensive women; however, as opposed to pregnancy-induced hypertensive women, those with chronic hypertension reassumed their humoral response to upright posture, which was accompanied by a significant reduction in sodium excretion. The parallelism between plasma renin activity and aldosterone levels, absent in normal pregnancy, returned in pregnancy-induced hypertensive and chronic hypertensive women in the erect posture (r = 0.73, p less than 0.01; r = 0.68, p less than 0.01, respectively). These data suggest that the adoption of the left lateral recumbent position in pregnancy reduces mean arterial pressure only in chronic hypertensive women. Moreover, in chronic hypertension, the upright position provoked a significant response of the renin angiotensin-aldosterone system. This effect was not observed in women with pregnancy-induced hypertension. PMID- 1735599 TI - Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein. AB - In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions. The apparent EC50 values and maximal responses to 30 nM endothelin were 1.4 nM and 0.96 g for endothelin-1, 5.2 nM and 0.65 g for endothelin-2, and 1.7 nM and 0.62 g for endothelin-3 (n = 4-12). At concentrations producing half the contraction triggered by 80 mM KCl, the order of potencies was endothelin-1 greater than U46619 = angiotensin II greater than bradykinin greater than substance P greater than phenylephrine. Longitudinal portal-mesenteric vein preparations developed very modest contractions to endothelin-1 (0.13 g at 30 nM; n = 5), but their responses to 80 mM KCl and phenylephrine were greater than those of rings. Responses of rings to endothelin-1 were profoundly reduced in Ca(2+)-free medium, but less inhibition was obtained after incubation with nicardipine (up to 1 microM) and/or nickel (up to 0.5 mM), phorbol (up to 0.3 microM), staurosporine (up to 10 nM), or cromakalim (3 microM). Indomethacin (5.6 microM) did not affect responses to endothelin-1. Cromakalim (0.1-3 microM) also relaxed rings constricted with 0.3 nM endothelin-1, and this effect was partially reversed by glibenclamide (3 microM). Thus, endothelins, especially endothelin-1, are potent constrictors of portal vein rings but not of portal-mesenteric vein strips. Their action appears to rely largely on Ca2+ influx from the external medium (only in part via L- and T-type Ca2+ channels) and activation of protein kinase C but not on eicosanoid generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735600 TI - Effects of 1 M NaCl cerebroventricular injection on renal and baroreceptor reflex functions. AB - Our purpose was to study the influence of the stimulation of the cerebroventricular system on some mechanisms related to hydrosaline equilibrium and blood pressure regulation. Renal function and blood pressure (group 1) as well as the baroreceptor reflex (group 2) were studied. In group 1, we measured diuresis, natriuresis, creatinine clearance, lithium clearance, and blood pressure in control rats and after stimulation of the cerebroventricular system with 1 M NaCl solution. In group 2, we evaluated the baroreceptor reflex, producing an increase of blood pressure with an injection of phenylephrine to obtain baroreceptor reflex curves--characterized by threshold, point of inflection, heart period range, gain, and systolic pressure corresponding to half the heart period range (SBP50)--in control and experimental rats injected with saline and 1 M NaCl solution, respectively. In group 1 experimental rats, we observed a significant increase in diuresis, natriuresis, blood pressure, and glomerular filtration rate. A substantial increase was also registered in sodium filtered load and reabsorbed sodium in the proximal convoluted tubule and distal nephron. No differences were observed either in fractional proximal tubule or in distal nephron sodium reabsorption. In group 2 experimental rats, mean arterial blood pressure, threshold, point of inflection, and SBP50 were significantly higher than in control rats. By contrast, a decrease in gain and heart period range was observed. No difference was obtained in heart rate. Our results demonstrate that the increase of the natriuresis is due, at least in part, to an increase in sodium filtered load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735601 TI - Sister chromatid exchanges and chromosome aberrations in lymphocytes of nurses handling antineoplastic drugs. AB - Chromosomal aberrations (CA) and sister-chromatid exchanges (SCE) were investigated in peripheral lymphocytes of 15 nurses and nurse's aides handling cytostatic agents in hospital oncology units. Significantly increased frequencies were noted for both CA and SCE rates when the exposed individuals were compared with 15 nurses working in other hospital units and to a control sample matched by sex and age. This points to the need for emphasizing protective measures in the handling of anti-neoplastic agents. PMID- 1735602 TI - Plasminogen activator system in human breast cancer. AB - We measured antigen levels of 2 kinds of plasminogen activator, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (UK), as well as those of their primary inhibitors, type-I plasminogen activator inhibitor (PAI-1) and type-2 plasminogen activator inhibitor (PAI-2), in tissue extracts from benign and malignant breast tumors. Tumor tissue samples from 40 fibroadenomas and 40 breast cancers were examined. t-PA antigen levels were the same in the 2 groups. Malignant tumors contained higher levels of UK antigen than did benign tumors. In the case of breast cancer, UK antigen levels of tumors with axillary lymph-node involvement were significantly higher than those of tumors without lymph-node involvement. PAI-1 and PAI-2 antigen levels of breast-cancer tissue samples were higher than those of fibroadenoma samples. PAI-1 antigen levels of carcinomas with lymph-node involvement were also significantly higher than those of carcinomas without node involvement. PAI-2 antigen levels, on the contrary, were higher in carcinomas without node involvement. UK, PAI-1 and PAI-2 antigen levels are potentially excellent independent factors for prediction of the metastatic potential of breast cancers. PMID- 1735603 TI - Association between childhood rhabdomyosarcoma and maternal history of stillbirths. AB - A case/control study of childhood rhabdomyosarcoma (RMS) was conducted utilizing information from birth records. Cases among Connecticut residents age 19 and younger diagnosed between 1960 and 1988 were identified from the Connecticut Tumor Registry files. Connecticut birth certificates were located for 103 of the 130 cases identified. A random sample of control birth certificates was frequency matched to the cases by year of birth, sex, and ethnic origin, with a control:case ratio of 2:1. Information abstracted from birth certificates included birth weight, length of pregnancy, plurality, birth order, mother's prior stillbirths, mother's age, father's age, and father's occupation. Data were analyzed by conditional logistic regression. The major finding was an association between RMS and the mother having had one prior stillbirth or more (odds ratio = 3.7; 95% confidence interval = 1.5 to 8.9). Particularly noteworthy was the observation that 6 mothers of cases, but no mothers of controls, had had 2 or more prior stillbirths. The trend for increasing risk of RMS with increasing number of mother's prior stillbirths was highly significant (p = 0.0004). This association suggests that RMS and a class of stillbirths share a common etiologic factor. This factor may be genetic or may involve in utero exposure to an exogenous or endogenous agent. PMID- 1735604 TI - Smoking and colorectal cancer risk: data from the Melbourne Colorectal Cancer Study and brief review of literature. AB - Lifetime smoking data were obtained from 715 colorectal cancer cases and 727 age/sex matched community controls as one part of a large, comprehensive, population-based study of colorectal cancer aetiology and survival in Melbourne, Australia, The Melbourne Colorectal Cancer Study. Statistically significant associations were found for those males smoking handrolled cigarettes and for cigar-/pipe-smoking males with colon cancer. Review of 18 previous case control studies of colorectal cancer showed an elevated risk for cigar-smoking black males in one study, a statistically non-significant increased risk for current smokers in one of 3 cohort studies and a statistically significant elevation of risk for smokers in 2 of 3 studies of adenomatous large-bowel polyps. Although at present there is insufficient evidence to link smoking with large-bowel cancer, the possibility that ingested tobacco is in some way carcinogenic for the colorectal mucosa may be worth further study. PMID- 1735605 TI - Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium. AB - We have isolated a new monoclonal antibody (MAb), K1, that reacts with an epitope on the surface of human ovarian carcinoma cells. This antibody was generated by immunization of mice with periodate-treated human ovarian carcinoma (OVCAR-3) cells. These mice had been previously made tolerant with normal human kidney membranes. Spleen lymphocytes from these mice were selected prior to fusion using a panning purification method on living OVCAR-3 cells. Initial screening of surface-reactive clones was performed in a single day using immunofluorescence on living OVCAR-3 cells, and secondary screening was performed using immunoperoxidase histochemistry on cryostat sections of normal human tissues and human tumors. The K1 clone was subcloned and identified as an IgM isotype, but was subsequently isotype-switched to IgG1K using a panning selection method. When evaluated by immunohistochemistry, the antigen reactive with K1 was found in many ovarian non-mucinous tumors, as well as in squamous tumors of the esophagus, and cervical cancer. The only normal adult human tissues showing uniform reactivity with K1 were the mesothelia of the peritoneal, pleural and pericardial cavities. There was also limited reactivity with epithelia of the trachea, tonsil and Fallopian tube. A similar tissue reactivity for K1 was found in tissues from cynomolgus monkeys. K1 reacted with many of the same tissues and tumors as the previously identified antibody OC125, but several lines of evidence indicate that K1 reacts with a different epitope and probably a different molecule, when compared to OC125. This evidence included assays employing immunofluorescence competition, double-label immunofluorescence, and solid-phase and live-cell radioimmunoassays. Since our data indicate that the antigen reactive with the K1 antibody is a new molecular species, we have named the antigen CAK1. Unlike the shed antigen CA125, CAK1 was only cell-associated and was not found in the supernatant of cultured OVCAR-3 cells or in the blood of ovarian cancer patients. The K1 antibody may be useful as a targeting agent for therapy and in the diagnosis of ovarian carcinoma, as well as some other human cancers. PMID- 1735606 TI - Infrequent mutation of the ras genes in skin tumors of xeroderma pigmentosum patients in Japan. AB - By using PCR amplification and oligonucleotide mismatch hybridization, base substitution mutations of the ras genes in 26 skin tumors of Japanese xeroderma pigmentosum (XP) patients were studied. Thin sections of tumor tissues which were fixed and embedded in paraffin blocks were used in this study. After analyzing codons 12, 13 and 61 of the H-, K- and N-ras genes by using 66 oligomer probes, we detected only one mutation of the K-ras gene at codon 61 in one tumor sample. All the other tumors were therefore considered not to have a mutation in the ras genes. These results suggest that mutations of the ras genes are not particularly associated with skin tumors of Japanese XP patients. PMID- 1735607 TI - Immunological analysis of 17 beta-hydroxysteroid dehydrogenase in benign and malignant human breast tissue. AB - The expression of 17 beta-hydroxysteroid dehydrogenase (17-HSD) enzyme protein was studied in benign and malignant human breast tissue using the time-resolved immunofluorometric assay (IFMA), immunoblotting and immunohistochemistry. The presence and distribution of estrogen and progestin receptors was also analyzed immunohistochemically. Cytosolic 17-HSD concentrations in malignant breast specimens were highly variable (less than or equal to 0.2-311 ng/mg protein). As was previously found for the placental enzyme, the molecular weight of the 17-HSD expressed in malignant breast tissue was 35 kDa, estimated following polyacrylamide gel electrophoresis and immunoblotting. The cellular distribution of 17-HSD was further studied by immunohistochemistry. Immunostaining for 17-HSD was observed in 71% of the benign breast lesions (fibroadenomas and cases of mastopathia chronica) and in 47% of the cancer specimens (intra-ductal carcinomas, invasive ductal carcinomas). In benign lesions, the staining was exclusively localized in the cytoplasm of epithelial cells, with no immunoreactivity in the stromal cells. The staining in the cancer specimens was also detected only in the cytoplasm of malignant epithelial cells. A strong or moderate expression of 17-HSD was related to the presence of PR in the specimen (chi 2 = 4.657, p = 0.031). However, the expression of PR was not a prerequisite for expression of 17-HSD in all the cancer specimens. Our data suggest that, in addition to the reported regulation of 17-HSD by progestins, other factors are also involved in this process in breast tissue. PMID- 1735608 TI - Identification and immunochemical characterization of IgA in sera of patients with mammary tumors. AB - It has been reported that several types of human cancer are associated with elevated levels of class-A immunoglobulins (Ig) and IgA-containing immune complexes. Moreover, most previous work has come up against the lack of IgA reactivity for chemically defined antigen (Ag). To overcome this, we first evaluated possible immunological binding in sera of patients with mammary tumors or malignant hematologic diseases and controls on a mouse monoclonal anti idiotypic antibody (Ab2), internal image of conjugated benzo(a)pyrene (BP) coated on well plates. Using this indirect ELISA, a statistically highly significant immunological binding was found in sera of patients with mammary tumors of every grade, type and size. This immunological binding was linked to the IgA isotype. Second, we performed competition experiments between a BP conjugate coated on well-plates and anti-anti-"BP-like" antibodies (Ab) previously incubated with rabbit idiotypic antibodies (Ab1) directed against conjugated BP. A part of these anti-anti-BP-like Ab, raised in rabbits immunized with human IgA of patients with mammary tumors, recognized the Ag-combining site of polyclonal Ab1, previously developed in a rabbit immunized with BP conjugates. It appears that part of the human Ig from sera of patients with mammary tumors shares common idiotopes with rabbit polyclonal Ab1 raised against conjugated BP. PMID- 1735609 TI - Fatty-acid composition of breast and iliac adipose tissue in breast-cancer patients. AB - In order to determine to what extent the fatty-acid composition of breast adipose tissue is representative of the body-fat composition in breast carcinoma, we compared the fatty-acid composition of breast adipose tissue to that of iliac fat in breast-cancer patients. Triglycerides from the 2 sites were purified by thin layer chromatography and fatty-acid composition was determined by capillary gas chromatography. Compared with iliac fat, mammary fat was higher in saturated (33.2 +/- 3.9 vs. 24.4 +/- 1.6%; p = 0.0001) and lower in mono-unsaturated (48.0 +/- 2.2 vs. 54.8 +/- 2.7%; p = 0.0001) and poly-unsaturated fatty acids (16.6 +/- 3.7 vs. 18.0 +/- 3.1%; p = 0.0001). A positive correlation was found between the 2 sites for linoleate (r = 0.95; p = 0.0003), alpha-linolenate (r = 0.83; p = 0.01), palmitate (r = 0.78; p = 0.02) and palmitoleate (r = 0.76; p = 0.02). No relationship was observed for stearic and oleic acids. We conclude that breast and iliac fat differ with regard to fatty-acid composition. The interpretation of fatty-acid composition of the body stores in breast-cancer patients, as an indicator of long-term intake of dietary fat, should take into account the sampling site of stored lipids. PMID- 1735610 TI - Clinical and biological significance of HSP89 alpha in human breast cancer. AB - In order to isolate and characterize genes whose expression may be altered in breast malignancy, we screened a cDNA library with a polyclonal anti-serum against breast-cancer-metastasis membranes and isolated several immunopositive clones. One of these, AJ1, was analyzed in detail and found to be expressed at varying levels as a 3.3-kb mRNA in all of 143 breast cancers. High expression was associated with lymph-node involvement (p = 0.03). Comparison between high- and low-expressing groups showed a significant difference at 4 and 6 years for both overall (p = 0.004 and p = 0.002 respectively) and disease-free (p = 0.0001 and p = 0.04 respectively) survival, but not at 11 years. AJ1 was expressed at much lower levels in non-malignant biopsies as compared with malignant tissue (p = 0.001). Expression was observed in breast-cancer cell lines MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL 100. Partial sequence analysis of the 620 bp clone showed complete homology with human heat-shock protein 89 alpha. In addition to being heat-inducible in all the breast cell lines examined, AJ1 levels were increased by estradiol (blocked by cyclohexamide and tamoxifen), EGF, oxytocin and vasopressin in a time-dependent manner in MCF-7 cells and by estradiol, EGF, prolactin and hydrocortisone in T47D cells. In MDA-MB-231 cells, EGF caused down regulation of AJ1 mRNA levels. The increasing evidence for the association of heat-shock proteins with steroid receptors suggests that AJ1 may play an important role in the control of estrogen-receptor transcriptional activity in breast cancers. PMID- 1735611 TI - Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-class in vivo. AB - Mouse-human chimeric monoclonal antibodies (MAbs) of 3 different human IgG sub classes directed against carcinoembryonic antigen (CEA) have been produced in SP 0 cells transfected with genomic chimeric DNA. F(ab')2 fragments were obtained by pepsin digestion of the purified chimeric MAbs of human IgG1, IgG2 and IgG4 sub class and of parental mouse MAb IgG1. The 4 F(ab')2 fragments exhibit similar molecular weight by SDS-PAGE. They were labelled with 125I or 131I and high binding (80 to 87%) to purified unsolubilized CEA was observed. In vivo, double labelling experiments indicate that the longest biological half-life and the highest tumour-localization capacity is obtained with F(ab')2 from chimeric MAb of human IgG2 sub-class, whereas F(ab')2 from chimeric MAb IgG4 give very low values for these 2 parameters. F(ab')2 from chimeric MAb IgG1 and from parental mouse MAb yield intermediate results in vivo. Our findings should help to select the appropriate human IgG sub-class to produce chimeric or reshaped MAb F(ab')2 to be used for tumour detection by immunoscintigraphy and for radioimmunotherapy. PMID- 1735612 TI - Regulation of natural antibody binding and susceptibility to natural killer cells through Zn(++)-inducible ras oncogene expression. AB - Changes in the natural resistance phenotype were examined for the 2H1, 10T 1/2 cells expressing the activated human H-ras oncogene under the transcriptional regulation of the zinc-inducible mouse metallothionein-I promoter. Culture of the cells in 50 microM ZnSO4 induced an increase in ras protein p21 levels which were maximal within 1 day. Natural-antibody (NAb) binding was significantly increased following 2 days of cell culture in ZnSO4 and continued to increase up to 4 days. The increased NAb binding returned to uninduced levels within 2 days following the removal of added zinc ions from the culture medium. The cells also exhibited a significant increase in natural killer (NK) cell sensitivity following 2 days in ZnSO4. This was maintained as long as the zinc was in the medium, but returned to uninduced levels within 1 day following its removal. The results show that NAb binding and susceptibility to NK cells increased following ras oncogene expression in 10T 1/2 cells and that both parameters were regulated by p21 expression. Repeated i.v. administration of whole-serum NAb prior to tumor inoculation reduced the number of early tumors following s.c. injection of Zn(++) induced 2Hl cells into Zn(++)-treated C3H/HeN mice, consistent with an in vivo role for NAb in the defense against ras-transformed cells. In contrast, small but statistically significant reductions in NAb binding were observed following v-H ras transformation of NIH 3T3 cells or v-src transformation of 10T 1/2. The data argue for an NAb- and NK-cell-susceptible phase of ras-induced tumor development which is a prerequisite for these mediators to contribute to a first line of defense against incipient neoplasia, and suggest that characteristics of the recipient cell and the transforming oncogene are important in determining the natural resistance phenotype. PMID- 1735613 TI - Interleukin-1 produced by tumorigenic fibroblasts influences tumor rejection. AB - Oncogene-transformed BALB/c-3T3 fibroblasts which spontaneously or upon immune activation with cytokines and lipopolysaccharide (LPS) generate IL-1 alpha, were tested for their tumorigenicity as well as their interaction with natural immune defense by NK cells and macrophages. Oncogene-transformed fibroblasts were weakly tumorigenic, since not all mice developed tumors despite application of high doses of tumor cells. This was independent of the immune status of the host. However, in the immunocompetent host those transformed fibroblast lines which spontaneously produced IL-1 alpha grew only transiently and then regressed. After induction of IL-1 alpha production, a decrease in the rate of tumor take was noted and the rate of regression of developing tumors was increased. Regression of IL-1-producing transformed fibroblasts was strongly reduced but not completely abolished in sublethally irradiated mice. This indicated that IL-1 production may predominantly influence T-cell-mediated defense, but some influence on non adaptive immunity could not be excluded a priori. IL-1 production did not influence susceptibility of transformed fibroblasts towards NK cells and macrophages. However, IL-1-producing transformed fibroblasts were most potent stimulators of NK cells and macrophages, the stimulatory effect being locally restricted. In conclusion, IL-1 producing, oncogene-transformed fibroblasts which generated the cytokine constitutively or upon immune-activation, were rejected from the tumor-bearing host following initial growth. Fibroblast-induced local activation of NK cells and macrophages was shown to play some role in tumor graft rejection. The influence of IL-1 production of transformed fibroblasts on T-cell mediated defense is addressed in the accompanying report. PMID- 1735614 TI - Induction of synthesis of manganous superoxide dismutase in L-M(pNTnF) cells carrying an inducible TNF gene. AB - Based on findings that the cytotoxic effects of tumor necrosis factor (TNF) are closely related to levels of intracellular oxygen radicals, and on the results of TNF gene transfection studies, the hypothesis was made that endogenous TNF (enTNF) acts as a protective factor against exogenous TNF by inducing inhibitors or scavengers of oxygen radicals. In order to test this hypothesis, we investigated the intracellular levels of manganous superoxide dismutase (MnSOD) and glutathione (GSH) in L-M(pNTnF) cells carrying a TNF gene induced by dexamethasone (DM). When L-M(pNTnF) cells were treated with DM they expressed enTNF, and acquired resistance to exogenous TNF. There was no change in the GSH concentration after enTNF induction, but a 1.9- to 3.9-fold increase in MnSOD levels was noted. Our findings suggest that enTNF exerts its protective function against the cytocidal effect of exogenous TNF by inducing MnSOD production. PMID- 1735615 TI - Influence of dose and schedule on the therapeutic efficacy of 131I-labelled monoclonal antibody 139H2 in a human ovarian cancer xenograft model. AB - The therapeutic efficacy of various doses and schedules of 131I-labelled anti episialin monoclonal antibody (MAb) 139H2 was assessed in the NIH:OVCAR-3 human ovarian cancer xenograft model. Radioimmunotherapy was started at the time s.c. tumors were well established (100 to 300 mm3). The anti-tumor effects induced by i.v. injections of 131I-MAb 139H2 were dose- and schedule-dependent. Optimal growth inhibition and long-lasting complete tumor regressions were obtained with 2 injections of 500, 700 or 750 muCi 131I-MAb 139H2 per mouse given with a 2-week interval. The percentage of tumors with more than 50% reduction of their initial volume after treatment with a total dose of 1,000 muCi 131I-MAb 139H2 per mouse, given as 10 injections of 100 muCi (3 x/week), 4 injections of 250 muCi (2 x/week), 10 injections of 100 muCi (5 x/week) within a period of 3 weeks, or 2 injections of 500 muCi with a 2-week interval, was 9%, 40%, 64% and 75% respectively. Unlabelled MAb 139H2 did not affect tumor growth, while the effects of 131I-control MAb were minor and transient. 131I-MAb 139H2 treatment did not select for outgrowth of episialin-negative cells in the OVCAR-3 xenografts. Highest absorbed doses of whole-body-radiation were calculated for 2 injections (500 to 750 muCi 131I-MAb 139H2) given with the 2-week interval. The radiation dose to the tumor after a single injection of 500 muCi 131I-MAb 139H2 was 1,300 cGy over 7 days, which appeared slightly lower than the dose calculated after administration of a tracer dose of iodinated MAb 139H2. PMID- 1735616 TI - Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells. AB - Intrathymic inoculation of radiation-leukemia virus (RadLV) into C57BL/6 mice induces a population of pre-leukemic (PL) T cells which progress into clonal, mature thymic lymphomas after a latency period of 3 to 5 months. In order to understand how PL cells are retained in the thymus for a prolonged period of time we determined whether RadLV infected cells secrete and/or respond to a T-cell growth factor that may be involved in the long-term maintenance of a thymic PL cell pool. We have previously found that in vitro proliferation of RadLV-infected PL cells is IL-4-dependent. Here we show that RadLV induces IL-4 secretion and IL 4 receptor (IL-4R) expression in normal thymic lymphocytes. RadLV-infected PL thymocytes express IL-4R and secrete IL-4. Their IL-4 secretion could be enhanced if incubated in the presence of RadLV and this enhancement was inhibited by anti RadLV antibodies. Several RadLV-induced lymphoma lines secreted IL-4 and/or expressed IL-4R, but these features were not essential for their continuous growth. The results suggest that RadLV induces IL-4-dependent autocrine growth which maintains a population of PL T cells in the thymus. Transition from a PL state to overt thymic lymphoma involves emancipation of a PL cell from IL-4 dependency. PMID- 1735617 TI - Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors. AB - We studied the effect of quercetin (Q) on the proliferation of HT-29, WiDr, COLO 201, and LS-174T human colon cancer cell lines. Q, between 10 nM and 10 microM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G0/G1 phase. Using a whole-cell assay with 17 beta-[3H]-estradiol as tracer, we demonstrated that all these cell lines contain type-II estrogen binding sites (type-II EBS). By using Q and other chemically related flavonols (3,7-4'-trimethoxyquercetin, 3,7,3',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-II EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-II EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-II EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers. PMID- 1735618 TI - Combination therapy with thymosin alpha 1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice. AB - In this study we have investigated the effects of thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57Bl/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of T alpha 1 plus IL-2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long-term survival in all treated animals. Depletion of immune cells, using either total-body sub-lethal irradiation (400 rads) or antibodies directed against T-cell (anti-CD4 and CD8) or NK-cell (anti-asialo GM1) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo-immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well circumscribed area of necrosis consisting solely of dead cells. Our studies show that T alpha 1 potentiates IL-2-induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti-tumor action when associated with chemotherapy. PMID- 1735619 TI - The persistence of poverty under welfare states and the prospects for its abolition. AB - This article examines the relationship between poverty and the welfare state and attempts to answer the question as to why poverty has persisted under all welfare states. Several major reasons for the persistence of poverty are advanced, and the author argues that the main factor underlying the failure to abolish poverty is the conflict between economic policy and social policy. The challenge to welfare states from the New Right is examined--particularly the contention that welfare states themselves create poverty and dependence--in the light of evidence of the impact of the Thatcher government's policies in Britain. Finally, the author proposes an alternative approach to the abolition of poverty, one that is based on the integration of economic and social policy. PMID- 1735620 TI - The political and moral economy of aging: not such strange bedfellows. AB - The authors develop E.P. Thompson's concept of moral economy as a useful complement to contemporary political economic analysis in problem areas involving moral conflict. Defined as the shared assumptions underlying norms of reciprocity in which an economic system is grounded, moral economy is seen as holding particular relevance for the study of aging. The evolution of pension systems, the "senior revolt" against catastrophic coverage in the United States, and debates over the allocation of health resources between generations are used to illustrate the utility of a combined political and moral economy for enriching our understanding in these areas. Marx's concept of a "morality of emancipation" is described as holding particular promise for the development of a new moral economy of old age that would move beyond alienation by giving broad attention to quality of life issues at each stage of the life course. PMID- 1735621 TI - Toward a political and moral economy of aging: an alternative perspective. AB - A conceptual framework for empowerment of the elderly is proposed, using variations on Gramsci's hegemony and Thompson's moral economy to complement recent political economic and social psychological theories. The political economy and social psychology of aging highlight structural constraints and actors' reactions without articulating a model for empowerment. Gramsci's idea of hegemony as new moral and philosophical leadership calls for principles of social and economic organization deserving assent because they maximize people's chances for a decent life at all ages. Hegemony, as normalizing dominance, reveals ways in which the elderly may be disempowered as well as possibilities for intervention. Underlying diverse forms of hegemony are economic arrangements and an array of cultural norms. In contrast to Thompson, the authors argue that norms implicit in moral economy vary with changes in social context. In the process, two ideal types of moral economy are elaborated, grounded in exchange value and use value, respectively. Empowerment may be found through a moral economy grounded in use value appropriate to advanced industrial society that is consonant with Gramsci's new hegemony. Implications for health and income maintenance policies are explored. PMID- 1735622 TI - Kerala State, India: radical reform as development. AB - Kerala State in southwestern India has achieved some of the third world's best rates of life expectancy, literacy, and infant mortality, despite one of the lowest per capita incomes. Especially notable is the nearly equal distribution of development benefits to urban, rural, male, female, high-caste, and low-caste sections of the populations. An even population distribution, a cosmopolitan trading history, and the development of militant worker and small farmer organizations led by dedicated activists provide the main explanations for Kerala's achievements. Land reform has redistributed wealth and political power from a rich elite to small holders and landless laborers. Public food distribution at controlled prices, large-scale public health actions, accessible medical facilities, and widespread literacy combine with and reinforce each other to maintain and expand Kerala's achievements. Serious unemployment threatens the Kerala experiment, but Kerala nonetheless offers important lessons to development planners, policymakers, and third world activists. PMID- 1735623 TI - Infant mortality and crisis in Mexico. AB - Data derived from the Encuesta Nacional de Fecundidad y Salud (ENFES) confirm that overall levels of infant mortality in Mexico have been steadily declining. However, a more specific analysis furnishes evidence that this decline has occurred at varying rates within different social groups, reflecting an increase in social inequalities. The analytical strategy used in this article leads to three basic conclusions: (1) the impact of the economic crisis on infant mortality is reflected not in a reversal of the declining trend but an increase in social inequalities; (2) certain variables universally accepted as determinants of infant mortality, such as mother's education, seem nonsignificant for some social sectors; and (3) certain biodemographic characteristics assumed to have a uniform mortality-related behavior vary among sectors, suggesting that even these constants are determined by social factors. PMID- 1735624 TI - Report of the commission on health research for development and the countries of the south. AB - Of late, governments of affluent countries have become more brazen in using United Nations organizations and other global commissions as tools to serve their political and economic interests. WHO and UNICEF have been used by these governments to impose technocentric and dependence-promoting programs on countries of the South. The report of the Commission on Health Research for Development is yet another effort in that direction. It advocates international cooperation in health research. It merely adds to the bulk of documents on international health research. It is ahistorical. It does not analyze why WHO and UNICEF and the governments of affluent countries imposed global programs on immunization and diarrheal and respiratory diseases without bothering to gather even the most elementary data about them. There is a method in the brashness. Worse still, it ignores the rich heritage of health research of the past half a century in countries such as India, Indonesia, and Thailand. It is yet another effort to obscure the message of self-reliance contained in the Alma-Ata Declaration on Primary Health Care. PMID- 1735625 TI - Malaria eradication and the selective approach to health care: some lessons from Ethiopia. AB - Analysis of the failure of the World Health Organization's global malaria campaign has contributed to the formulation of the primary health care concept as the basic international strategy for health improvement. The Primary Health Care Conference held in Alma-Ata in 1978 was to have ended the period of vertical disease control programs, such as the one against malaria, stressing instead the integration of these programs into horizontal community-based health systems. Malaria control programs, however, have not been integrated well--or in some cases at all--into primary health care networks. An analysis of the Ethiopian experience, as part of the worldwide malaria eradication program, illustrates the political and economic forces that have worked against the move from vertical to integrated malaria control activities, and from vertical to integrated health programs more generally. PMID- 1735626 TI - Struggle and revolt in the Spanish health policy process: the changing role of the medical profession. AB - Many changes have taken place in the professional status and political role of the Spanish medical profession during the process of construction of the health care system (1940-1990). There is a strong correlation between the different characteristics of the several phases of construction of the national health care system and some of the changes in the status, organization, and political activity of the medical profession. The democratic transition coincided with changes in the orientation of the system brought about by financial imperatives, which forced readjustments in the survival and political projects of the profession. The creation of a democratic regime has allowed the medical profession to create its own independent mechanisms of interest representation and has given rise to a process of negotiation of the new political relations (and their mechanisms) between the State and the profession. The last 15 years have witnessed important transformations in some parameters of the profession, in its political organization, its political role, and its relation with the State. PMID- 1735627 TI - The welfare state, class, and gender. AB - If we compare the welfare state countries with others, from the point of view of both health and health services, the crisis concerns primarily the second group of countries. Nevertheless, difficulties arise also for welfare state policies. The problem is how to respond to neoconservative attacks on social and health rights, and how to change the bureaucratic and medicalized bias of the welfare state. The "golden era" of social insurance and health services, conceived as free access to funds to cope with all the growing needs of the population, is over. Limitations, controls, and priorities have to be established. In Italy and similar countries, the tendency is toward restricting health care for those who have greater needs, cutting funds for prevention, and creating greater inequalities. It is clear that the state must intervene to reduce social inequalities, but at the same time some existing differences (sexual, cultural, ethnic) have an intrinsic value that must be recognized. A policy of free-choice welfare is useful, and has nothing to do with the selective measures that are being introduced. Moreover, a key point has become the relationship between class and gender. The working class continues to be exploited, but new phenomena arise, connected with production and social reproduction and not limited to this sphere. It is true that gender includes social classes, but no social class may represent both sexes, or different ethnic groups, or gender itself. PMID- 1735628 TI - The drug lag issue: the debate seen from an international perspective. AB - This article reviews the literature related to the "drug lag" issue, i.e., the issue of whether important new drugs are introduced relatively late, or, in certain cases, are introduced at all, in a particular country. The literature can be divided into two main parts: studies primarily related to the delay in introduction of new drugs and studies primarily related to the number of introduced new drugs. Most studies have found the United States, Sweden, and Norway to have a long delay in the introduction of new drugs. The United Kingdom and (West) Germany in general have the shortest delay. There are also large differences in the number of introduced new drugs. In most studies, the United States and Norway have introduced far fewer new drugs than any other industrialized country. In general (West) Germany, France, the United Kingdom, and Italy have introduced the largest number of new drugs. One of the reviewed studies presented a relationship between regulatory processing time and delay in introduction. Another study found an increasing influence of regulatory stringency on the number of introduced new drugs in a country. If a country's aim is to decrease the delay in introduction and/or to increase the introduction of important new drugs, a review of the local regulatory agencies and the regulations seems worthwhile. PMID- 1735629 TI - The other who is also the same: the relevance of epidemics in space and time for prevention of HIV infection. AB - The history of epidemics reveals the imposition of controls over time and space on the sick and powerless other in the interests of the well and powerful same. In contrast, effective prevention requires the sharing of values, space, and time: coevality in the broadest sense. Adolescents are seen as merely transitional: they were children in the recent past, they will be adults in the recent future. Thus as an other who must become the same, they are seen as out of time and threatening. Conventional adults fear uncontrolled sexuality, especially if it is perceived as taking place out of time and is therefore anachronistic or in the wrong places, out of bed and through the wrong orifices (anatopistic). These unshared cultural perceptions are a barrier against both education for life and effective prevention of HIV infection. PMID- 1735630 TI - The new corporate health ethic: lifestyle and the social control of work. AB - A corporate health ethic, forged in U.S. industry in the 20th century, clearly demarcated boundaries between private and workplace health concerns. This article advances evidence that the boundary is blurring, and argues that trends in workplace initiatives, including employee assistance, wellness programs, and drug screening, are giving shape to a new corporate health ethic. The new ethic emphasizes workers' lifestyles on and off the job, engendering a shift in corporate jurisdiction over employee health and behavior. Economic arguments such as "health care cost containment" are commonly offered as explanations for these new health initiatives. But the authors see the new ethic as a deeper response to a changing corporate environment and, more fundamentally, as emblematic of changes in the social control of work and productivity. They argue that the new health ethic may be a harbinger of new forms of social control in the workplace. PMID- 1735631 TI - IMS, ISBA cooperation yields new laws on advance directives. AB - Iowans have greater control over their medical care, thanks to the cooperative efforts of the Iowa State Bar Association and the Iowa Medical Society. PMID- 1735632 TI - 'Code of civility' for attorneys, physicians. AB - Representatives of the ISBA and IMS ar working on a modern version of 1956 vintage practice principles governing lawyer-physician relationships. PMID- 1735633 TI - An interview with the president of the ISBA. PMID- 1735634 TI - Clinical use of adenosine. AB - Adenosine (Adenocard) is a new injectable antiarrhythmic agent indicated for the acute treatment of paroxysmal supraventricular tachycardia (PSVT) including PSVT associated with the Wolff-Parkinson-White syndrome. Many physicians are not yet familiar with its actions, indications and side effects. PMID- 1735635 TI - Patient Self-Determination Act. PMID- 1735636 TI - Sexual harassment in the workplace: minimize your liability. PMID- 1735637 TI - A physician's day in court: 2 perspectives. PMID- 1735638 TI - Instrumentation control and automation in the control of biological effluent treatment. AB - The role of instrumentation, control, and automation (ICA) in the management, operation, and control of domestic and industrial wastewater treatment works is examined following an historical account of developments in the UK over the past two decades. Included also are aspects of process optimization and process selection, taking into account size and types of works and populations served. The particular ICA requirements of individual unit processes are examined and the effects of unattended operation and remote supervision are considered. Particular attention is paid to measurement technology, the shortcomings of available instruments and systems, and recent developments of relevance, with particular emphasis being placed on microelectronic and fibre- and electro-optic-based sensors and on the role of advanced commenting methods including expert systems. Progress with biologically based sensors is also discussed. PMID- 1735639 TI - Generalized multiple-regression techniques with interaction and nonlinearity for system identification in biological treatment processes. AB - A class of multiple regression models, called "generalized multiple-regression" (GMR) is proposed. GMR has the advantages of being easy and rapid to fit, and uses standard multilinear regression software. It has an advantage over ARIMA models in modeling nonlinearity and linear and nonlinear interactions among variables. Its main disadvantage is that, if there are many independent variables, the reduction of degrees of freedom may be important. It is less parsimonious than other models, but availability of increased computational power makes this not a serious disadvantage. The GMR models are compared to autoregressive transfer function models and feedforward back propagation neural network models. In the case of modeling effluent volatile suspended solids, GMR models were superior to both linear autoregressive models and neural network models. The neural network models did, however, outperform the linear models. In the case of modeling sludge volume index, both GMR and the neural network model were unable to improve upon ARIMA models. It was concluded that ARIMA models may, in some cases, produce the most parsimonious model, but in other cases they may miss important process behaviors. The GMR models showed robust capability to describe complex data. PMID- 1735640 TI - Neutron response of a polyethylene-moderated superheated drop detector. AB - Monte Carlo neutron transport calculations were performed to obtain the neutron response functions of a superheated drop detector (SDD-100) that is surrounded by polyethylene of various thicknesses. The calculational results suggest that a SDD 100 surrounded by 2.54 cm of polyethylene gives the best dose-equivalent response in a free neutron field. Results were confirmed by a sequence of experiments using various neutron sources. This polyethylene-moderated SDD-100 is ideal for use as an area neutron dose monitor. PMID- 1735641 TI - Detection and determination limits for thermoluminescence dosimetry. AB - The statistical theory of detection and determination limits is applied to thermoluminescence dosimetry (TLD), and equations are derived for calculating the limits. Three different levels of testing a TLD system are described, and a test procedure is given for each level. An example from a working system is presented, and the dependence of detection and determination limits on background radiation exposure is shown. The results show the importance of clearly defining the terms used to describe the low-dose performance of a TLD system. PMID- 1735642 TI - Application of glow curve analysis methods to improve TLD-100 dose reassessment performance. AB - This paper presents a method of improving the TLD-100 dose reassessment performance. This method consists of applying numerical analysis techniques for evaluating the TLD-100 phototransferred thermoluminescence (PTTL) glow curve. From this analysis, a simple procedure for estimating the ultraviolet background components usually present in phototransferred thermoluminescence (TL) signals has been established. This procedure has been implemented in a computer program which performs the automatic evaluation of the glow curves and extracts the dose information contained in the PTTL curves. The use of this computer-aided evaluational method has enabled the extension of the working range of estimated absorbed dose down to 0.2-0.5 mGy with very adequate operational quality for doses even below the conventionally admitted lower reestimation limit (approximately 2 mGy). Because TL readout is a destructive process, the ability to reestimate doses can be important in any kind of dosimetric activity, such as operational dosimetry programs. The other commonly used dosimeter, film, uses a nondestructive readout and, therefore, presents some advantages over TLD when dose reassessment is necessary. With the reported improvements in the TLD-100 dose reassessment performance, the full range of absorbed doses covered by film dosimetry can now be reliably reassessed using TLD-100 dosimeters. PMID- 1735643 TI - Discovery of a 137Cs hot particle in municipal wastewater treatment sludge. AB - Analysis of primary treatment sludge from a municipal wastewater treatment plant revealed elevated 137Cs concentrations in one sample. This elevated activity was associated with a radioactive particle that, when isolated and quantified, was found to contain 1.82 kBq of 137Cs. Additional analysis indicated an absence of alpha activity, and energetic beta radiation, if present, was less than the 137Cs activity. The particle was approximately 50 microns in diameter, appeared not to be an aggregate, and was nonmetallic. PMID- 1735644 TI - Calculating the calibration coefficient for radon measurements with the bare LR 115-II track detector. AB - Model calculations were performed to determine the calibration coefficient for radon measurements using a bare LR 115-II track detector. Calculations were based on an expression for stopping power for heavily charged particles, as well as on the Monte Carlo method. The sensitivity of the LR 115-II detector depends on equilibrium factor F, and it has been calculated for various values of F. For equilibrium factor F = 1, the calibration coefficient in this calculation was 89 m-1 (10.3 Bq d m-3 per tracks cm-2) for the removed layer, which was 5.5 microns thick. PMID- 1735645 TI - Behavior of Chernobyl fallout radionuclides in peat combustion. AB - The fallout from the explosion and fire at the Chernobyl nuclear power plant concentrated levels of up to 10 kBq 137Cs kg-1 dry weight in the fuel peat harvested during the summer of 1986 in Finland. We investigated the behavior of fallout radionuclides 137Cs, 134Cs, 106Ru, 144Ce, 125Sb, 95Zr, and 110mAg together with naturally occurring 210Pb and 226Ra in the combustion of this contaminated peat in four different power plants. The elements antimony, ruthenium, lead, and cesium were enriched on the smallest particles, indicating that they were in a volatile chemical form, while cerium, zirconium, and radium were nonvolatile at the combustion temperatures. This result confirms the previous finding that ruthenium is volatile in combustion. Although metallic ruthenium requires 2,310 degrees C to melt, some of its oxides melt and evaporate at much lower temperatures. PMID- 1735646 TI - Mathematical aspects of a rotating point source with an application to megavoltage shielding. AB - This study developed the mathematics of a rotating point source. The relative dose and the dose rate were numerically evaluated at various positions along the cardinal axes, both with and without a 1-m-thick concrete barrier. The point source model was compared to experimental data gathered at an operational megavoltage radiation therapy facility. PMID- 1735647 TI - Analyzing uranium concentrations in drinking water samples in India using the fission-track technique. AB - The "dry" fission-track registration method was used to analyze uranium concentrations in drinking water samples collected from various water sources in some cities of India. A nuclear track detector made of plastic was used for registering fission tracks. Results showed a uranium concentration in drinking water of 0.67-20.26 micrograms L-1. PMID- 1735648 TI - Mortality among workers at Oak Ridge National Laboratory. PMID- 1735649 TI - Mortality of workers at the Oak Ridge National Laboratory. PMID- 1735650 TI - A juggling act with values of maximum permissible concentration of radionuclides in air and water. PMID- 1735651 TI - Effects of two types of head coverings in the rewarming of patients after coronary artery bypass graft surgery. AB - In this experimental study we examined the effects of two types of head coverings in the rewarming of patients who have had coronary artery bypass graft surgery during the initial 8-hour postoperative period. A third group with no head coverings served as a control. Eighty-one patients were randomly assigned to one of the three treatment groups; rectal temperatures were recorded on admission and hourly for the next 8 hours. An analysis of variance between the three groups revealed no statistically significant differences (p less than 0.05) in the length of time for patients to reach normothermia and in the net temperature gain achieved. Irrespective of the groupings, however, patients who took 5 hours or less to reach normothermia exhibited statistically significant differences (p less than 0.05) compared with patients who took longer: the former patients tended to be younger, the lowest induced operating room temperature tended to be higher, their admission temperatures tended to be higher, and minutes of cardiopulmonary bypass tended to be fewer. PMID- 1735652 TI - Comparability of the thermodilution cardiac output method: proximal injectate versus proximal infusion lumens. AB - In this study we examined the relationship between cardiac output (CO) measurements obtained from the proximal injectate lumen and the proximal infusion lumen of a thermodilution pulmonary artery catheter. The research was predicated on the belief that a strongly significant relationship would provide the clinician with an alternative lumen for measuring CO. Twenty-one subjects were selected by using a nonprobability convenience sampling method. With ice temperature injectate, four injections were performed into one lumen followed by four injections into the alternate lumen. CO values were computed with installed data management physiologic monitors. A Pearson's Product-Moment Correlation Coefficient was calculated, and the result verified a strong positive correlation between CO values (r = 0.96, p = less than 0.0001). Results of a paired t test demonstrated no statistically significant differences between CO means. These findings lend direction for minimizing the potential risk of catheter contamination associated with the manipulation of intravenous lines containing vasoactive medications. It also may save time for the critical care clinician who is trying to balance tasks such as CO measurements and titration of vasoactive or inotropic medications. PMID- 1735653 TI - The association between interdisciplinary collaboration and patient outcomes in a medical intensive care unit. AB - We prospectively studied the relationship between interdisciplinary collaboration and patient outcomes in the medical intensive care unit (MICU) using nurses' and residents' reports of amount of collaboration involved in making decisions about transferring patients from the MICU to a unit with a less intense level of care. Either readmission to the MICU or death was considered a negative patient outcome. Nurses' reports of collaboration were significantly (p = 0.02) and positively associated with patient outcome, controlling for severity of illness. Patient predicted risk of negative outcome decreased from 16%, when the nurse reported no collaboration in decision making, to 5% when the process was fully collaborative. There was an interaction of collaboration with availability of alternative choices in the transfer decision-making situation. When alternatives were available, collaboration was more strongly associated with patient outcome. There was no significant relationship between residents' reports of collaboration and patient outcomes. The correlation between amount of collaboration reported by nurses and residents about the same decisions was quite low (r = 0.10). PMID- 1735654 TI - Empathy of intensive care nurses and critical care family needs assessment. AB - In this study we explored the relationship between the empathy of intensive care unit (ICU) nurses and their ability to assess accurately the perceived needs of family members of patients hospitalized in ICU settings. Thirty family needs were studied by using Molter's 1983 revision of the Critical Care Family Needs Inventory (CCFNI). Data consisted of 92 pairs of CCFNI responses obtained from 92 family members of ICU patients and 60 ICU nurses providing direct care for these patients. Multiple regression analysis was performed to determine the extent to which empathy and nursing experience contribute to accurate assessment of the needs of ICU family members. The more emphatic ICU nurses were, the greater their ability to assess ICU family members' needs accurately on six of the needs studied (p less than or equal to 0.05). Length of nursing experience negatively affected the nurse's ability to assess three of the ICU family members' needs accurately (p less than 0.05). PMID- 1735655 TI - The spouse: a factor in recovery after acute myocardial infarction. AB - Literature supports the concept that the response of a patient's spouse influences the recovery process of a patient after an acute myocardial infarction (AMI). This was a 6-month, longitudinal, descriptive study of 17 married couples in which one of the pair experienced his or her first AMI. The study examined the question: "Is there a relationship between the spouse's social support, family stress, marital satisfaction, and sexual comfort and the patient's recovery after AMI?" Data were collected at three times during the 6-month period after AMI. Results showed a significant relationship between the spouse's family stress, marital satisfaction, and sexual comfort and the patient's recovery. Also, a significant relationship was found between the spouse's sexual comfort and marital satisfaction. This was the first reported study that examined sexual comfort over time and investigated sexual activities other than intercourse. PMID- 1735656 TI - Ludwig's angina. AB - Ludwig's angina is a cellulitis frequently occurring as a result of infections of the second and third lower molar. Despite a decrease in mortality from 50% to less than 10% since the introduction of antibiotics, it remains a rare but life threatening illness. The potential for rapid respiratory obstruction is the greatest concern. Familiarity with the anatomy of the neck and recognition of symptoms are essential for effective treatment. Treatment focuses on maintenance of an airway, antibiotic therapy, and surgery. Asphyxia, aspiration, mediastinitis, pneumonia, empyema, and septicemia are possible complications. PMID- 1735657 TI - Assessing delirium in the acute care setting. AB - Delirium is a common, disruptive, costly, and at times lethal condition found among patients in the acute care setting. Nurses can be the first to discover its presence and thereby reduce the time to treatment. Identifying delirium requires a knowledge of its clinical features, a mastery of the bedside cognitive mental status examination, critical judgment in distinguishing delirium from other psychiatric disorders, and appropriate nursing interventions based on ongoing assessment. In this article we review elements of such an approach and illustrate common clinical challenges for nurses with case examples. PMID- 1735658 TI - Relationships among health beliefs, self-efficacy, and exercise adherence in patients with coronary artery disease. AB - Management of the pathologic progression of coronary artery disease requires life style changes in patients, but the level of compliance with medical recommendations is low. Critical care nurses have a unique opportunity to encourage patients to assume responsibility for their health care and life-style behavior. In this study we developed a model to identify the relationships among variables that explained adherence to a recommended exercise regimen. The variables studied included self-efficacy, perceived severity, barriers, benefits, and cues to action. PMID- 1735659 TI - Effect of venous support on edema and leg pain in patients after coronary artery bypass graft surgery. AB - The purpose of this study was to assess the effect of external venous support on edema and pain in the saphenous graft leg of patients who had coronary artery bypass graft surgery (CABG) 5 days and 1 month after surgery. Fifty-six patients who had CABG surgery were randomly assigned to the experimental (n = 24) or control (n = 32) group. Subjects in the experimental group wore graded compression support hose. Edema was assessed by using ankle, calf, and thigh circumference measurements. Pain was measured on a visual analog scale. Hose were effective in preventing edema during hospitalization, but results at 1 month were inconclusive. There was no difference in leg pain for experimental and control subjects. That a number of patients in the experimental group were unable to complete the study suggests that off-the-shelf, thigh-high support hose may not be useful for individuals with disproportionately large thighs. Further investigation of the long-term effects of support hose is warranted. PMID- 1735660 TI - Lung hyperinflation caused by inappropriate ventilation resulting in electromechanical dissociation: a case report. AB - Lung hyperinflation has been demonstrated to occur in patients with obstructive lung disease requiring mechanical ventilation. A dramatic case of pulmonary hyperinflation occurred in the early resuscitative period after initial intubation and manual ventilation leading to the development of electromechanical dissociation. Once the presence of lung hyperinflation was recognized, manipulation of the patient's ventilator settings allowed resolution of the lung hyperinflation and reversal of the detrimental hemodynamic effects it produced. This case illustrates that lung hyperinflation should be included in the differential diagnosis of electromechanical dissociation. In selected patients if pneumothorax, hypovolemia, cardiac tamponade, and myocardial infarction are excluded as causes and pulmonary hyperinflation is suspected, then a trial of adjusted ventilation to decrease the lung hyperinflation may be useful. PMID- 1735661 TI - Digoxin toxicity presenting as altered mental status in a patient with severe chronic obstructive lung disease. AB - Gastrointestinal and cardiac manifestations are the commonly considered features of digoxin toxicity. This report describes a patient with severe chronic obstructive lung disease whose primary manifestation of digoxin toxicity is acute alteration of mental status. Neurologic dysfunction may be the sole manifestation of digitalis toxicity. The diagnosis of digoxin toxicity should be considered in elderly patients with altered mental status, even when serum levels are within a therapeutic range. PMID- 1735662 TI - In-use comparison of latex gloves in two high-risk units: surgical intensive care and acquired immunodeficiency syndrome. AB - This study was designed to compare use patterns and leakage of gloves from two high-risk units: a surgical intensive care unit (SICU) and an acquired immunodeficiency syndrome (AIDS) unit. During a 3-month interval, the use of gloves during clinical procedures by nursing personnel was observed and recorded. A total of 2900 latex examination gloves were collected and tested in the laboratory by the watertight leakage test: 59% (1714) were from the SICU and 41% (1186) from the AIDS unit. Twenty-four percent (700) of all gloves leaked: 29% (500/1714) leaked when worn by staff in the SICU as compared with 17% (200/1186) leakage rate in the AIDS unit (chi-square = 57.32, p less than 0.05). This difference could be attributed in part to higher levels of stress to the gloves and longer wearing time in the SICU. PMID- 1735663 TI - Meningococcal conjunctivitis. PMID- 1735664 TI - Comparison of thermodilution and transthoracic electrical bioimpedance cardiac outputs. PMID- 1735665 TI - On the use of the moments method of estimation to obtain approximate maximum likelihood estimates of linkage between a genetic marker and a quantitative locus. AB - The approximate maximum likelihood method of Luo & Kearsey (1989) to determine the parameters of a segregating quantitative trait locus (QTL) in an F2 population by linkage to a genetic marker is compared to the 'true' maximum likelihood estimates derived by scanning the seven parameter likelihood space. The two methods did not yield identical results, and diverged markedly for a dominant QTL loosely linked to the genetic marker. Further study is suggested to evaluate other methods that do not simultaneously maximize the likelihood for all parameters. PMID- 1735666 TI - The Seventh International Conference on Chemical Modifiers of Cancer Treatment- Part I. Clearwater, Florida, 2-5 February 1991. PMID- 1735667 TI - Tissue oxygen manipulation and tumor blood flow. PMID- 1735668 TI - Measurement of oxygen diffusion distance in tumor cubes using a fluorescent hypoxia probe. AB - Oxygen diffusion distance was measured in solid tumor "cubes" prepared by excising the tumor from the mouse and incubating 1-2 mm sided tumor cubes in spinner culture flasks with fluorescent drugs (AF-2 or DM113) which bind to hypoxic cells. After incubation, frozen sections were prepared and examined for AF-2 or DM113 binding using a fluorescence image processing system. Alternatively, cubes were stained with a slowly penetrating fluorescent dye, Hoechst 33342, prior to disaggregation and measurement of AF-2 binding using flow cytometry. The distance from the cube surface to the AF-2 stained region (i.e., the thickness of the unstained rim) was used as an indication of oxygen diffusion distance, which depends on the square root of the tumor oxygen consumption rate. Oxygen diffusion distance was dependent on tumor type, external oxygen concentration, and temperature during incubation with AF-2, but was unaffected by tumor size up to 1.2 gm or position of the cube within the tumor. Oxygen diffusion distances (in planar geometry) measured for cubes prepared from SCCVII, RIF-1, Lewis lung or WiDr tumors were 107, 123, 153 and 193 microns, respectively. For SCCVII and WiDr tumors, the percentage of blood vessels separated by a distance greater than double the mean oxygen diffusion distance was used as an indication of the hypoxic fraction. PMID- 1735669 TI - Effect of carboxyhemoglobin on tumor oxygen unloading capacity in patients with squamous cell carcinoma of the head and neck. AB - Hemoglobin and blood gas parameters, with special attention to the influence of carboxyhemoglobin, were studied in 115 head and neck cancer patients undergoing radiotherapy. In 712 weekly blood samples, the values of total hemoglobin, carboxyhemoglobin (CO-Hb), and p50 were measured and the total oxygen content in the arterial and tumor venous blood was estimated. The difference between these values express the tumor oxygen unloading capacity (t-OUC). CO-Hb ranged from 0 12% and showed a significant inverse relationship with t-OUC. This was caused by a reduced amount of effective hemoglobin combined with a left shift of the oxyhemoglobin dissociation curve (reduced p50). Overall, the tumor oxygen utilization decreased from 70% to 52% as a function of an increase in CO-Hb from 0 to 12%. PMID- 1735670 TI - Reoxygenation associated radiosensitization after chronic hypoxia: effect of temperature and oxygen tension. AB - A431 human squamous carcinoma cells reoxygenated after 12 hr hypoxia were found to be more radiosensitive than aerobic cells not previously exposed to hypoxia. Experiments were carried out to investigate the effect of temperature and oxygen tension during the hypoxia and the reoxygenation periods on the sensitization effect. Incubation at 0 degrees C during 12 hr of hypoxia inhibited the sensitization seen after reoxygenation. During the reoxygenation period, reduced temperature did not modify the levels of enhancement but suppressed the decay of the sensitization. If oxygen tension during 12 hr of hypoxia was less than 10 ppm, maximal enhancement by reoxygenation was seen, but there was no enhancement if the oxygen concentration was greater than 1%. In cells subjected to less than 10 ppm oxygen for 12 hr, the level of sensitization by reoxygenation in 2 to 20% oxygen concentration was similar. The results indicate that radiosensitization by reoxygenation may require metabolic change(s) of cells during both the hypoxia and reoxygenation periods. The sensitization may also involve oxygen dependent species of reactions. PMID- 1735671 TI - Improving the radiation response in a C3H mouse mammary carcinoma by normobaric oxygen or carbogen breathing. AB - The limited therapeutic benefit from nitroimidazoles has renewed the interest in normobaric oxygen as a hypoxic cell radiosensitizer. In this experimental study we have tried to modify the oxygenation of a C3H mammary carcinoma by flushing tumor-bearing mice with oxygen or carbogen for 5 min before and during treatment. The response to these treatments was evaluated by the changes in radiation induced tumor control (TCD50) and by the changes in tumor hypoxic fraction (HF). Irradiation was given either as a large, single dose or as five equal, daily fractions. High levels of oxygen in the inspired air were found to decrease the TCD50 significantly. The enhancement ratios were in the range of 1.2-1.4 (p less than 0.05) for both single dose and fractionated irradiation, which suggests that hypoxic cells may be important even when reoxygenation is believed to be complete between fractions. The change in TCD50 corresponded to a decrease in the fraction of clonogenic hypoxic cells from 12% to 3-4% (p less than 0.05). Tumor blood flow was not significantly influenced by the gas treatment. This study thus shows that normobaric oxygen/carbogen inhalation may significantly improve the local tumor control by reducing the diffusion related hypoxia within tumors. PMID- 1735672 TI - Influence of carboxyhemoglobin level on tumor growth, blood flow, and radiation response in an experimental model. AB - Carboxyhemoglobin (HbCO) is formed when carbon monoxide is bound to hemoglobin. High levels of HbCO are known to reduce the amount of oxygen that can be carried to the tissues. This experimental study focuses on the influence of HbCO on the growth, blood flow, and radiation response of an experimental mouse tumor. The study was designed to mimic the clinical situation where heavy smokers are undergoing radiotherapy while having a high HbCO level. The tumor was a C3H mammary carcinoma grown in the feet of CDF1 mice. Chronic exposure to carbon monoxide, resulting in 10% HbCO, increased the tumor volume doubling time from 2.5 to 3.5 days (p less than 0.05). The acute exposure to carbon monoxide prior to and during irradiation significantly raised the radiation dose required to control the tumor locally. The TCD50 increased from 54 Gy in air breathing mice (HbCO 0-2%) to 57 Gy (HbCO 7-9%) and 61 Gy (HbCO 20-23%). This increase corresponded to an increase in the fraction of clonogenic hypoxic tumor cells from 0.12 in air breathing animals to 0.21 and 0.41, respectively. The tumor blood flow, determined by the 86RbCl extraction technique, decreased to 63% (n.s.) and 50% (p less than 0.05) for low and high HbCO levels, respectively. PMID- 1735673 TI - Flavone acetic acid as a modifier of endothelial cell function. AB - Flavone acetic acid (FAA) causes significant regression of larger established tumors in murine systems in vivo, but is only slightly toxic in vitro. This in vivo effect is thought to be indirect, or immunological, rather than a direct cytotoxic effect on tumor cells. Using the WHFIB fibrosarcoma, which grows both in vivo and in vitro, and the murine endothelial cell line B10, we have studied the effect of FAA on the survival of tumor and endothelial cells in vitro. The times taken for 1 mg ml-1 FAA to reduce survival to 0.1 surviving fraction were 63 hr for B10 and greater than 85 hr for WHFIB in vitro. WHFIB tumors in vivo were more sensitive than tumor cells in vitro, a single dose of 150 mg kg-1 FAA inducing a tumor growth delay of 10 days at treatment size + 2 mm. As FAA is more toxic to tumor-bearing animals than to those which are non-tumor bearing the effect of tumor conditioned medium on the cytotoxicity of FAA toward B10 cells was studied; no enhanced effect was seen. As FAA is only weakly cytotoxic in vitro to endothelial cells, and even less so to tumor cells, sublethal effects of FAA on endothelial cell function in vitro were studied. The permeability of monolayers of human unbilical vein endothelial cells (HUVEC) in vitro is transiently increased by FAA. Also, procoagulant activity of HUVEC is induced by FAA and this activity is further enhanced in the presence of a factor isolated from Meth-A tumor cells. PMID- 1735674 TI - A comparison of vascular-mediated tumor cell death by the necrotizing agents GR63178 and flavone acetic acid. AB - A vascular component of tumor damage has been identified for the anticancer agent GR63178. The necrotizing activity of this drug and of flavone acetic acid has been compared with their ability to induce growth delay in six murine tumor models. At 24 hr, after a fixed dose of flavone acetic acid (200 mg/kg), all six tumor types appeared 80-100% necrotic histologically, although growth delays ranging from 3 to 79 days were measured. GR63178 (200 mg/kg) induced more variable degrees of necrosis (10 to 95%), but a uniformly small delay in growth (0 to 4 days). These data illustrate that the absence of a tumor-growth response should not be automatically equated with an absence of drug activity. Without assessing tumor response histologically, agents with unusual mechanisms of action may be missed, despite their potential for killing large numbers of tumor cells. PMID- 1735675 TI - Effects of calcium channel blockers on renal function in mice. AB - Tumor blood flow modification is currently under investigation as a possible means of optimizing current cancer therapies, with particular respect to improving the efficacy of bioreductive agents. A variety of calcium channel blockers have been shown to modify tumor perfusion in model systems, and may be valuable as potentiators of both bioreductive and conventional drugs. We report the effects of nifedipine, verapamil, flunarizine, and cinnarizine on renal function in C3H mice, assayed by clearance of simultaneously injected 51Cr ethylenediamine tetraacetate. Nifedipine at 10 mg kg-1 blocked 51Cr ethylenediamine tetraacetate clearance for 30 min and reduced its subsequent rate of clearance by a factor (+/- 2 se) of 2.4 +/- 0.6. At 1 mg kg-1 it reduced the rate of clearance by a factor of 1.2 +/- 0.2. Verapamil at 10 mg kg-1 blocked 51Cr ethylenediamine tetraacetate clearance for 10 min and reduced its subsequent rate of clearance by a factor of 1.5 +/- 0.3, but had no effect at 1 mg kg-1. Flunarizine had no effect at 50 mg kg-1 or at 5 mg kg-1, but cinnarizine at 50 mg kg-1 reduced clearance rate by a factor of 1.2 +/- 0.1. The data show that some of these vasoactive agents, nifedipine and verapamil in particular, can severely compromise renal function and may, therefore, affect the plasma pharmacokinetics of co-administered drugs that are cleared by the kidney. PMID- 1735676 TI - Effect of flunarizine on micro-regional distributions of intravascular HbO2 saturations in RIF-1 and KHT sarcomas. AB - Flunarizine, a calcium channel-blocker, preferentially active on peripheral blood vessels and red blood cells, has previously been shown to increase not only tumor blood flow, but also both chemosensitivity and radiosensitivity. The mechanisms behind these effects are not clear at present, and different tumor lines have been demonstrated to respond quite differently to the same flunarizine treatment. To clarify the underlying mechanisms at the micro-regional level, the present investigation examined the effects of flunarizine on spatially-resolved distributions of intravascular oxyhemoglobin (HbO2) saturations. Tumors were implanted s.c. in the flanks of C3H mice and grown to a volume of 500-1000 mm3. Flunarizine was injected i.p. at 5 mg/kg; animals were anesthetized, and following a 20 min delay, tumors were quick-frozen. HbO2 saturations were determined cryospectrophotometrically at systematically selected sites across each tumor cross-section. Three primary questions were addressed: (a) Does flunarizine have a direct effect on tumor oxygen delivery as measured by intravascular HbO2 saturations? (b) Are changes in oxygen delivery uniformly distributed throughout the tumor volume? (c) Are HbO2 distributions for tumor lines of dissimilar radiobiological hypoxic fraction affected similarly by flunarizine? For KHT tumors, flunarizine substantially increased the % vessels greater than or equal to 10% saturated throughout the tumor volume, with a somewhat larger increase for the interior vessels than for the peripheral vessels. In contrast, for the RIF-1 tumors, HbO2 saturations following flunarizine remained near control levels. These results indicate that fundamental differences in vascular geometry, hemodynamics, or blood rheology may exist between the KHT and RIF-1 tumor lines, and furthermore, that the response of one tumor line to a given blood-flow modifier may be completely unrelated to that of another. PMID- 1735677 TI - Relationship between the hydralazine-induced changes in murine tumor blood supply and mouse blood pressure. AB - The relationship between hydralazine-induced changes in blood pressure and tumor blood flow was investigated in restrained but non-anesthetized CDF1 mice bearing C3H/Tif foot tumors. Mean arterial blood pressure measurements were made using the procedure of carotid cannulation, and tumor blood flow was estimated using laser Doppler flowmetry. Hydralazine doses from 0.1 to 5.0 mg/kg were tested. Following hydralazine administration the maximum changes in blood pressure and blood flow were apparent within 10-15 min and were maintained for at least 30 min after injection. Blood pressure decreased with increasing hydralazine dose, achieving a maximum reduction of 50% at 2.5 mg/kg. Tumor blood flow was found to be increased by 30% at the lowest hydralazine dose (0.1 mg/kg), even though blood pressure was decreased by 10% at this dose. At hydralazine doses producing a 15% or greater blood pressure drop, blood flow decreased, reaching an 80-90% reduction between 2.5 and 5.0 mg/kg. PMID- 1735678 TI - Tumor blood flow changes induced by chemical modifiers of radiation response. AB - This study was designed to investigate blood flow changes induced by chemical agents that are commonly used in combination with radiation therapy. The hypoxic cell cytotoxin RSU 1069 at a dose of 100 mg/kg was shown to reduce blood flow by 80% in both SCCVII and C3H mammary tumors. Blood flow reductions of 30-40% were also observed in both tumors following administration of the radiation sensitiser pimonidazole (Ro-03-8799) at a dose of 500 mg/kg. Moreover studies in the C3H mammary tumor indicated that this effect was tumor size-dependent, being more profound and of longer duration in 500 mg than in 100 mg tumors. Blood flow decreases were also observed in the SCCVII tumor after administration of adriamycin at a dose of 15 mg/kg. Blood flow decreased by over 80% immediately after drug administration but recovered to remain 20% below control values 1 hr after drug administration. In contrast to the other agents studied, cis platinum at a dose of 2 mg/kg produced a small 20-30% increase in blood flow which persisted over the 1 hr observation period. The potential implications of these findings are discussed. PMID- 1735679 TI - Blood flow modification in the SCCVII tumor: effects of 5-hydroxytryptamine, hydralazine, and propranolol. AB - The effects of hydralazine, 5-hydroxytryptamine (5-HT), and propranolol on blood flow in the SCCVII tumor were assessed using laser Doppler flowmetry. Both hydralazine and 5-HT, at doses of 1 and 5 mg/kg, reduced blood flow, as did propranolol at 10 mg/kg. Hydralazine and 5-HT at doses of 0.25 mg/kg slightly increased tumor blood flow, and a 10-20% increase in blood flow was also observed after 1 mg/kg of propranolol. However, propranolol at 1 mg/kg enhanced the blood flow reduction observed with 1 mg/kg of hydralazine. The concomitant administration of hydralazine and propranolol at these doses also translated into increased potentiation of the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069. PMID- 1735680 TI - Magnetic resonance spectroscopy studies on experimental murine and human tumors: comparison of changes in phosphorus metabolism with induced changes in vascular volume. AB - The responses of two experimental murine tumors and two human tumor xenografts to the vasodilator hydralazine were compared using two magnetic resonance spectroscopy endpoints. Changes in tumor metabolism were determined using 31P MRS where inorganic phosphate levels relative to total phosphate (Pi/total) were measured, and alteration in tumor blood volume was examined using 19F MRS with perfluorooctylbromide (PFOB) as tracer. The integrated 19F signal from PFOB is dose dependent and stable for at least 2 hr after injection. The murine tumors SCCVII/Ha and KHT both showed changes in tumor metabolism after hydralazine, as an increase in Pi/total. However, hydralazine reduced vascular volume in the KHT tumor, demonstrated by reduced 19F signal from PFOB, but no such reduction was seen in the SCCVII/Ha tumor. In contrast, hydralazine had no effect on phosphorus metabolism in the HT29 and HX118 human tumor xenografts, but reduced vascular volume in both tumors. These results demonstrate that the effects of vasoactive agents such as hydralazine on tumor phosphorus metabolism are only partially consistent with changes in vascular volume, measured by the 19F MRS technique. PMID- 1735681 TI - The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy. AB - 31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents. PMID- 1735682 TI - Determination of changes in tumor blood perfusion after hydralazine treatment by dynamic paramagnetic-enhanced magnetic resonance imaging. AB - Magnetic resonance imaging, using the paramagnetic chelate gadopentetate dimeglumine as a perfusing agent, was used to investigate the effect of the vasoactive drug hydralazine on tumor blood perfusion. The method requires measurements of the magnetic resonance image intensity changes with time on a pre selected region of interest in the tumor image, immediately following intravenous injection of gadopentetate dimeglumine. The present study showed that the initial slope of the intensity-time curve can be used, to a first approximation, to infer tumor blood perfusion. With the dynamic imaging technique, it was demonstrated that, in the KHT sarcoma implanted intramuscularly in the hind leg of C3H/HeN mice, intraperitoneal administration of hydralazine reduced the volume-averaged tumor blood perfusion in a dose-dependent manner. The intrinsically high spatial resolution of magnetic resonance imaging allows a detailed study of the heterogeneous nature of tumor blood perfusion. The potential applications of this imaging technique to study the differential effects of hydralazine on perfusion between tumor and normal tissues will be discussed. The clinical utility of the technique should be promising because of its non-invasive nature. PMID- 1735683 TI - Biochemical modification of therapeutic response. PMID- 1735684 TI - Measurement of incorporation of bromodeoxyuridine into DNA by high performance liquid chromatography using a novel fluorescent labelling technique. AB - 5'-Bromo-2-deoxyuridine (BUdR) is a halogenated pyrimidine analogue that is an efficient radiosensitizer through its incorporation into DNA in place of thymidine. Radiosensitization is proportional to percentage replacement and we present here a novel derivatization technique that specifically labels the thymidine and BUdR with 4-bromomethyl-7-methoxycoumarin (BrMMC) to give the highly fluorescent coumarin derivatives which are quantitated using high performance liquid chromatography (HPLC). This allows for a simple single-stage DNA hydrolysis and sensitive peak detection. Data are presented showing the incorporation with time of BUdR into the DNA of Chinese hamster V79 cells. Attention is also drawn to the care needed in the selection of enzymes required for DNA digestion. PMID- 1735685 TI - Iododeoxyuridine incorporation and radiosensitization in three human tumor cell lines. AB - Iododeoxyuridine is a halogenated pyrimidine and non-hypoxic cell radiosensitizer currently being used in clinical trials. The amount of radiosensitization by IdUrd is related to the amount of incorporation of the drug into a cell's DNA. These experiments were carried out in three human tumor cell lines (lung, glioma, and melanoma) in monolayer culture exposed to concentrations of IdUrd from 0.1-10 microM for one and three cell cycles before irradiation to determine incorporation and sensitization as a function of drug exposure. Except for the lung cell line, which required greater than 1 microM IdUrd, these cells demonstrate radiosensitization when exposed to 0.1 microM or greater of IdUrd. Maximum sensitization occurred at 10 microM IdUrd for all the cell lines at three cell cycles. The percent thymidine replacement by IdUrd increased with increasing concentrations, but was cell line dependent. Maximum percent replacement occurred at 10 microM at three cell cycles for all the cell lines: lung = 22.4%, glioma = 32.0%, and melanoma = 39.1%. The relationships between percent thymidine replacement and sensitization are not identical across these human tumor cell lines. If IdUrd is going to be a successful radiosensitizer in clinical trials, sustained plasma levels of 10 microM or greater for at least three cell cycles should be achieved during irradiation. This may be best accomplished with repeated short exposures to IdUrd (three cell cycles or approximately 4 days in these cell lines) every 1-2 weeks during radiation. Measurements of thymidine replacement in a tumor biopsy should be attempted prior to radiation to develop a predictive assay for radiosensitization. PMID- 1735686 TI - Correlation of sensitizer enhancement ratio with bromodeoxyuridine concentration and exposure time in human cervical carcinoma cells treated with low dose rate irradiation. AB - The effect of a range of bromodeoxyuridine concentrations and exposure times on the sensitizer enhancement ratio of two human cervical carcinoma cell lines treated with low rate irradiation was evaluated. Both cell lines show a linear, though different, dose response to low dose rate irradiation at dose rates up to 0.62 Gy/hr. Cells were pre-incubated with 0, 1, 5, or 10 microM bromodeoxyuridine for 0, 24, or 48 hr prior to low dose rate irradiation. Based on the survival of cells exposed to 4 Gy, delivered at 0.62 Gy/hr, a slope was determined for an exponential survival curve for each bromodeoxyuridine concentration and exposure time. Sensitizer enhancement ratios were calculated as the ratio of the slopes of the treated and untreated cells from a particular exposure time. Ratios increased linearly initially with a plateauing at higher levels with respect to the product of bromodeoxyuridine concentration and time of exposure for both cell lines with similar degrees of enhancement. A linear relationship has been noted previously for acute irradiation of hamster cells over a similar range of sensitizer concentrations and exposure times. At the highest dose-time points (540 microM hr) ratios of greater than 2 were attained, which were comparable to results obtained following acute radiation exposures of V-79 cells. These results demonstrate that significant sensitizer enhancement ratios with low dose irradiation can be obtained in human tumor cells after exposures of 2 to 3 doubling times using relatively low concentrations of sensitizer. PMID- 1735687 TI - Modulation of iododeoxyuridine-mediated radiosensitization by 5-fluorouracil in human colon cancer cells. AB - The incorporation of 5-iodo-2'-deoxyuridine (IdUrd), a thymidine analog radiosensitizer, can be increased by the use of modulators such as 5-fluorouracil (FUra). FUra is a particularly attractive potential modulator to use against colorectal cancer, as it is the most active single agent in the treatment of this disease. To begin to define the conditions for the optimal combination of IdUrd and FUra in the treatment of patients with colorectal cancer, a study was conducted of the effect of FUra on IdUrd-mediated radiosensitization in cultured HT29 human colon cancer cells. It was found that when cells were exposed to concentrations of IdUrd typical of those obtained through intravenous exposure (1 3 microM), FUra (1 microM) increased radiosensitization beyond that which would be predicted for the same extent of incorporation produced by incubation with IdUrd alone. This increase appeared to result from a combination of at least two effects: FUra-mediated cell cycle redistribution and increased IdUrd incorporation. When a higher concentration of IdUrd (10 microM) was used with FUra (1 microM), cell cycle distribution returned to nearly normal, and radiosensitization was equal to that predicted by the extent of incorporation of IdUrd. These data demonstrate that the combination of FUra and IdUrd can produce radiosensitization both through increased IdUrd incorporation and cell cycle redistribution. Furthermore, they suggest that, in the presence of a modulator, it may not be necessary to achieve high levels of IdUrd incorporation to produce significant tumor radiosensitization. PMID- 1735688 TI - 5-chlorodeoxycytidine, a radiosensitizer effective against RIF-1 and Lewis lung carcinoma, is also effective against a DMBA-induced mammary adenocarcinoma and the EMT-6 tumor in BALB/c mice. AB - 5-Chlorodeoxycytidine (CldC), coadministered with modulators of pyrimidine metabolism, is an effective radiosensitizer of murine tumors. Past studies that utilized RIF-1 tumors in C3H mice and Lewis lung carcinoma (LLC) in BDF1 mice have been extended with an emphasis on using multiple cycles of drug administration followed by irradiation of LLC and the use of two additional tumor models. Four of seven cures of BDF1 mice bearing LLC were obtained with three doses of 20 Gy irradiation, in which the first and third dose were preceded by a "Standard Protocol" that includes N-(phosphonacetyl)-L-aspartic acid (PALA), 5 fluorodeoxycytidine (FdC), tetrahydrouridine, and the radiosensitizer, 5 chlorodeoxycytidine. No cures were obtained in groups of mice receiving radiation alone or drugs alone, and there were no "no takes" in untreated control groups (six mice/group). Extensive tumor inhibition, exceeding that obtained with drugs or radiation alone, was obtained with two cycles of drugs and radiation combined when a dimethybenzanthracene-induced mammary adenocarcinoma was used in BALB/c mice. With the EMT-6 tumor in BALB/c mice, doses of 10 and 20 Gy were administered 9 and 16 days after tumor implantation, each preceded with the Standard Protocol; this resulted in a tumor growth delay of 24 days. No tumor growth delay occurred with drugs or radiation alone. The omission of PALA, FdC or CldC from the Standard Protocol resulted in loss of tumor control, which was obtained with the complete protocol. The fact that 5-chlorodeoxycytidine is an effective radiosensitizer in four rodent tumor systems is compelling evidence that it has potential as a radiosensitizer of human tumors, especially in view of its tumor selectivity and its resistance to catabolism when used with modulators of its metabolism, and in view of the high levels of the key enzymes in human tumors, which can convert 5-chlorodeoxycytidine to 5-chlorodeoxyuridine triphosphate, the proximate radiosensitizer. PMID- 1735689 TI - Phase I study of high dose 5-fluorouracil and high dose Leucovorin with low dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. AB - Twenty-eight patients with refractory advanced malignancies were treated with a 24 hr infusion of 5-fluorouracil (5-FU), Leucovorin (LV), and N-(phosphonacetyl) L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable for the assessment of toxicity and anti-tumor activity. PALA was administered as intravenous bolus over 15 min at a fixed dose, 250 mg/m2 24 hr before the start of 5-FU and LV infusions. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 2600 mg/m2. LV was administered in a fixed dose of 500 mg/m2 concurrently with 5-FU over a 24-hr period. The course was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among dose-limiting toxic effects. Other toxicities observed were hand-foot syndrome, hair loss of scalp/eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. Maximum tolerated dose (MTD) of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated at 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose de escalation, a majority of whom contained 5-FU at a dose of 2100 mg/m2. Twenty three of 27 patients had been previously treated. Eight patients achieved a partial response, all of whom were previously treated, except three patients. A complete response was observed in a patient with pancreatic carcinoma, previously untreated. Overall response rate for the patients who were treated at the 5-FU dose of 2100 mg/m2 or 2600 mg/m2 is 9 of 18 patients (50%). PMID- 1735690 TI - Cell cycle dependence of epidermal growth factor induced radiosensitization. AB - The effect of epidermal growth factor on the radiation response of two human squamous carcinoma cell lines, A431 (from vulva) and SiHa (from cervix), was examined. In both lines, cells in S phase were more radioresistant than cells in other cell cycle phases. Epidermal growth factor present after irradiation enhanced the radiation response of A431 cells in different cell cycle phases, whereas no effect was seen for SiHa cells. The enhancement was maximum with 10 ng/ml epidermal growth factor and was associated mainly with a reduction in the shoulder region of the cell survival curve. The ratio between the n values of the control and epidermal growth factor treated total cell population, G1, S, and G2M cells is 2.2, 4.1, 1.7, and 2.2, respectively. Epidermal growth factor reduced plating efficiency by about 50% for A431 cells in different cell cycle phases whereas a slight increase in plating efficiency was seen for SiHa cells. The present results indicate that epidermal growth factor related radiosensitization is dependent on both cell line and cell cycle. PMID- 1735691 TI - Concepts and developments in radiosensitization of mammalian cells. PMID- 1735692 TI - Correlation of the radiosensitization potency afforded by nitroacridine intercalators with their electron scavenging efficiency in DNA. AB - Nitracrine (1-NC) and its nitro-positional analogues are electron-affinic DNA intercalating compounds that act as hypoxic cell radiosensitizers in cell culture, but are too rapidly metabolized to provide radiosensitization in vivo. We have explored the electron-trapping efficiencies of nitroacridines to see if such compounds can scavenge radicals formed in irradiated DNA and if the efficiency of such trapping is related to their radiosensitization properties. We have shown that a correlation does indeed exist as 1-NC, the most potent radiosensitizer, scavenges approximately 45% of the migrating electrons (formed by attachment of eaq- to the DNA) compared with approximately 4% for 4-NC, the least efficient radiosensitizer. The quenching of the delayed fluorescence from acridine orange bound to DNA was also used to probe intracellular uptake and association with DNA. The results are in accord with earlier measurements of average uptake and a suggestion that intercalators which form DNA complexes with short residence times will be preferable to highly bound agents as radiosensitizers. Since 1-NC possesses the smallest association constant with DNA of the four compounds, it is suggested that its high radiosensitization potency may well be related to it being able to interact with more radical sites on the DNA than the other analogues, in addition to its capture of migrating electrons in DNA. PMID- 1735693 TI - Mechanistic studies of enhanced in vitro radiosensitization and hypoxic cell cytotoxicity by targeting radiosensitizers to DNA via intercalation. AB - In an effort to increase the molar efficiency of 2-nitroimidazoles as hypoxic cell radiosensitizers and cytotoxins, they have been linked to a DNA intercalating group. The lead compound in this series, NLP-1, is a 2 nitroimidazole, linked at the one position to a phenanthridine ring system via a three carbon chain. Studies of the hypoxic cell specific radiosensitizing properties and hypoxic cell selective toxicity of NLP-1 toward CHO AA8-4 cells show the drug does have enhanced efficiency compared to the untargeted 2 nitroimidazole, misonidazole, based on external drug concentrations. To see if this enhanced efficiency was due to the proposed mechanism, targeting to DNA, or to a general increase in the intracellular concentration of the drug, its uptake and accumulation intracellularly were determined. Radioactive NLP-1 was synthesized labelled with 14C at the 2 position of the imidazole ring. Cells were incubated with the radioactive drug under aerobic and hypoxic exposure conditions, and intracellular levels of the drug were determined by a spin through-oil technique. Results indicated that, at a drug concentration of 0.5 mM, there was no net accumulation of the drug over the external drug levels after aerobic exposure. Under hypoxic conditions, the drug did accumulate intracellularly, presumably because of hypoxia specific drug metabolism. Experiments with radioactive misonidazole labelled with 14C in the 2 position of the imidazole ring were run as controls. These results suggest that, under the conditions used, NLP-1 has an increased molar efficiency as a hypoxic cell radiosensitizer and cytotoxin, compared to misonidazole, based on intracellular drug concentrations. PMID- 1735694 TI - Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908. AB - Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization. PMID- 1735695 TI - NLA-1: a 2-nitroimidazole radiosensitizer targeted to DNA by intercalation. AB - Targeting of electron affinic radiosensitizers to DNA via reversible non-covalent intercalative binding has potential for increasing sensitizer concentrations locally at the DNA target while decreasing accessibility to reductases responsible for bioactivation and cytotoxicity. We have prepared an DNA-targeted acridine-linked 2-nitroimidazole (NLA-1) as an example of such a compound. NLA-1 binds reversibly to DNA with an affinity similar to 9-aminoacridine, and is approximately 1000 times more potent than MISO as a cytotoxin, despite a similar reduction potential. It shows less enhancement of cytotoxicity under hypoxia (5- to 6-fold) than does MISO (approximately 11-fold), but is a potent hypoxia selective radiosensitizer in AA8 cells with a concentration for an enhancement ratio of 1.6 (C1.6) of 9 microM. The mean intracellular concentration at the C1.6 is 400 microM, on which basis its potency is about twice that of MISO. The in vitro therapeutic index (aerobic cytotoxic potency/hypoxic C1.6) of NLA-1 is approximately 6-fold lower than that for MISO. NLA-1 lacks radiosensitizing activity against SCCVII or EMT6 tumors in vivo at the maximum tolerated dose (MTD) of 100 mumol.kg-1. PMID- 1735696 TI - Radiosensitizing, toxicological, and pharmacokinetic properties of hydroxamate analogues of nitroimidazoles as bifunctional radiosensitizers/chemical modifiers. AB - We examined the pharmacokinetics of KIH-802, potassium 2-nitroimidazole-1 acetohydroxamate, using its radioisotope-labelled compound and the acute toxicity in mice. We discovered that the concentration of KIH-802 was very low in the brain and its LD50 was nearly half the value of that of MISO. We also present here new 2-nitroimidazole radiosensitizers/chemical modifiers (KIN-804, 811, 831, 841, 844, 821, 823 and 824) designed to enhance their sensitizing ability intensely by substituting various biologically active groups, such as hydroxamic acids and oximes, with moderate lipophilicity to the aromatic ring, if necessary, through some spacers. The sensitizing effects of all compounds were estimated to be almost equal to or better than that of MISO. The results of their toxicities shows that new hydroxamates KIN-804 and 831 are less toxic than KIH-802 and MISO. Their in vitro enhancement ratios are 2.00 and 1.75, respectively, compared with those of KIH-802, MISO and SR-2508, 1.77, 1.72 and 1.72, respectively, at each dose of 1 mM for EMT6/KU single cell. We concluded that they may be superior radiosensitizers of hydroxamic acid analogues to KIH-802. PMID- 1735697 TI - Intratumoral and parametrial infusion of a 3-nitrotriazole (AK-2123) in the radiotherapy of the uterine cervix cancer: stage II-III--preliminary positive results. AB - Based on a clinical differential effect of the action of a new hypoxic cell radiosensitizer, AK-2123 (a 3-nitro-1,2,4-triazole), on locally advanced cervix cancer (Stage II-B and III-B), a Phase I/II clinical trial has been carried out on 80 consecutive patients. They were intratumorally injected with AK-2123, wt 1% and 2%, 30 min before the delivery of external radiation therapy. The short-term effects show that exophytic types of lesions respond far better than endophytic types and AK-2123 may be replacing intracavitary radium for exophytic Stage II-B cervix cancer as the standard therapy for this neoplasm in our patients. Treatment is well tolerated and no neurological toxicity has been noted. PMID- 1735698 TI - Metabolic rate modification of nitrotriazole radiosensitizers by sulfur substitution of side chain. AB - The pharmacokinetic properties and radiosensitizing activities in vitro and in vivo of a series of 3-nitro-1,2,4-triazole (NTA) derivatives with a -CH2(C = Y)NH(CH2)nZCH3 (Y, Z = O or S; n = 2 or 3) group in the side chain at N-1 position of NTA were investigated with respect, particularly, to the effects of sulfur substitution in the side chain of NTA. The sulfur substitution for an oxygen atom in the side chain NTA radiosensitizers increased the rho value, but gave rise to little effect on the one-electron reduction potential. The derivatives bearing a thioether group (-CH2SCH3) in the side chain were slightly less effective both in vitro on hypoxic EMT6/KU cells and in vivo on SCCVII tumors than their oxygen analogs (-CH2OCH3). The thioether compounds tended to metabolize rapidly. The thioamide compound showed high sensitizing activity in vitro, but metabolized very slow. PMID- 1735699 TI - Fluorine modification of nitroazole radiosensitizers for the enhancement of sensitizing activity with lowering toxicity: a pharmacokinetic characterization. AB - Pharmacokinetic characterization of various nitroazole radiosensitizers was carried out to clarify the effect of fluorine modification of the side-chain groups on the sensitizing activity and the acute toxicity. The in vivo tumor/plasma partition coefficient (PTP) of sensitizers increased with increase in the octanol/water partition coefficient (Pow) up to approximately 0.3 and was almost unity (maximum) for sensitizers with their Pow values larger than approximately 0.3. This relationship was observed commonly for all types of sensitizers independent of the fluorine modification. The in vivo brain/plasma partition coefficient (PBP) of sensitizers increased with increase in the Pow, attaining a constant value of almost unity at Pow greater than 0.5 for non fluorine sensitizers or at Pow greater than 1.5 for fluorine-modified sensitizers. The maximum brain-affinity factor ((FB,t)max = (CB,t)max/Ds, where (CB,t)max and Ds are the maximum intrabrain concentration and the administered dose of sensitizer, respectively) was proportional to the maximum tumor-affinity factor ((FT,t)max = (CT,t)max/Ds, where (CT,t)max is the maximum intratumor concentration of sensitizer), depending on the side-chain structure of the sensitizer. A series of non-fluorine and fluorine-modified nitroazole derivatives, including N-(2'-hydroxyethyl)-2,2-difluoro-3-(3''-nitro-1' triazolyl)propionamide (KU-2285), gave a smaller brain to tumor ratio of approximately 1/7. The toxicity index defined by 1/LD50/7 was parallel to the sensitizing activity measured by 1/DS,1.5 (DS,1.5 is the sensitizer dose to obtain the SER of 1.5 in vivo). The therapeutic risk index defined by Ds,1.5/LD50/7 depended on the side-chain structures of sensitizers. The DB,1 5LD50-/7 values of KU-2285 and ethanidazole (SR-2508) were 1/3 that of misonidazole (MISO). The sensitizers were smaller Ds,1.5/LD50/7 values showed higher sensitizing activities as their tumor affinities increased, without an increase in serious toxicity. PMID- 1735700 TI - Combined modality treatment with ternary Cu(II) complexes and X rays. AB - Ternary Cu(II) complexes with bidentate malonato- and heterocyclic amine ligands were tested with regard to cytotoxicity and potentiation of x-ray induced cell killing in V79 cells. Two lead complexes were also tested in a tumor assay using the MTG-B murine adenocarcinoma model growing in the flanks of female C3H/HeJ mice. One complex, [2,2'-bipyridyl malonatoCu(II)] (RL-5077), produced sensitizer enhancement ratios (SER's) of 1.8 (hypoxic conditions) and 1.0 (oxic conditions) in vitro when irradiation followed 1 hr exposure to the drug at 100 microM. When RL-5077 was administered at doses of 1/2 (11.65 mg/kg) or 1/4 (5.25 mg/kg) the maximum tolerated dose (MTD), 15 min prior to a locally delivered dose of 20 Gy, enhancement ratios (ER's) of 1.6 and 2, respectively, resulted. The second lead complex, [1,10 phenanthroline (malonato)Cu(II)hydrate] (RL-5027), produced SER's of 1.8 and 1.2 under hypoxic and oxic conditions, respectively, at a concentration of 25 microM. Injection of RL-5027 (5 mg/kg) resulted in toxicity without enhancement in combination with radiation. Analogues of these two complexes have been synthesized in an effort to optimize the potentiation of radiation effects while minimizing toxicity to drug alone and increasing water solubility of the drug. Further studies of the structure-activity relationship of Cu(II) ternary complexes using in vitro radiosensitization as the endpoint have identified four classes of ligands with varying biological activity and have supplied information about the effects of group substitution on solubility, toxicity, and radiation potentiation. This group of complexes represents a new class of radiopotentiators that deserves further investigation into its potential for clinical use. PMID- 1735701 TI - Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme. AB - The present study determined whether inhibitors of angiotensin converting enzyme (ACE) can ameliorate radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a range of single doses of 60Co gamma rays to the right hemithorax. Four indices of pulmonary endothelial function were monitored: right lung ACE and plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Hydroxyproline (HP) content served as an index of pulmonary fibrosis. Rats consumed either control powdered chow or feed containing one of five modifying agents continuously after irradiation. The modifiers included three ACE inhibitors: Captopril, CL242817, and CGS13945, respectively, a thiol, a thioacetate, and a nonthiol compound. All of the ACE inhibitors are analogues of proline. Two additional modifiers were tested: penicillamine, a thiol with no ACE inhibitory activity; and pentoxifylline, a vasodilator that is neither a thiol nor an ACE inhibitor. Radiation produced a dose-dependent decrease in lung ACE and PLA activity, and an increase in PGI2 and TXA2 production and in HP content. All ACE inhibitors attenuated the radiation-induced suppression in lung ACE and PLA activity. All thiol or thioacetate compounds ameliorated the radiation-induced increase in PGI2, TXA2, and HP. The two agents that were both thiols and ACE inhibitors (Captopril and CL242817) spared all of the radiation reactions, while the compound that was neither a thiol nor an ACE inhibitor (pentoxifylline) spared none of the reactions. These data suggest a novel application for ACE inhibitors in general, and for Captopril in particular, as modifiers of radiation pneumotoxicity. PMID- 1735702 TI - American Society of Andrology, 17th annual meeting. March 27-30, 1992, Bethesda, Maryland. Abstracts. PMID- 1735703 TI - The Clp proteins: proteolysis regulators or molecular chaperones? PMID- 1735705 TI - Functional analysis of the sialyltransferase complexes in Escherichia coli K1 and K92. AB - The polysialyltransferase (polyST) structural gene, neuS, for poly alpha 2,8sialic acid (PSA) capsule synthesis in Escherichia coli K1 was previously mapped near the kps region 1 and 2 junction (S. M. Steenbergen and E. R. Vimr, Mol. Microbiol. 4:603-611, 1990). Present Southern and colony blot hybridization results confirmed that neuS was a region 2 locus and indicated apparent homology with neuS from E. coli K92, bacteria that synthesize a sialyl alpha 2,8-2,9 linked polymer. A K1- mutant with an insertion mutation in neuS was complemented in trans by K92 neuS, providing direct evidence that neuS encoded the PSA polymerase. A 2.9-kb E. coli K1 kps subclone was sequenced to better characterize polyST. In addition to neuS, the results identified a new open reading frame, designated neuE, the linker sequence between regions 1 and 2, and the last gene of region 1, kpsS. The kpsS translational reading frame was confirmed by sequencing across the junction of a kpsS'-lacZ+ fusion. PolyST was identified by maxicell analysis of nested deletions and coupled in vitro transcription translation assays. PolyST's derived primary structure predicted a 47,500-Da basic polypeptide without extensive similarity to other known proteins. PolyST activity was increased 31-fold and was membrane localized when neuS was cloned into an inducible expression vector, suggesting, together with the polyST primary structure, that polyST is a peripheral inner membrane glycosyltransferase. However, polyST could not initiate de novo PSA synthesis, indicating a functional requirement for other kps gene products. The existence of a sialyltransferase distinct from polyST was suggested by identification of a potential polyprenyl binding motif in a C-terminal membrane-spanning domain of the predicted neuE gene product. Direct evidence for a quantitatively minor sialyltransferase activity, which could function to initiate PSA synthesis, was obtained by phenotypic analysis of mutants with multiple defects in sialic acid synthesis, degradation, and polymerization. The results provide an initial molecular description of K1 and K92 sialyltransferase complexes and suggest a possible common function for accessory kps gene products. PMID- 1735704 TI - Mutation of the miaA gene of Agrobacterium tumefaciens results in reduced vir gene expression. AB - vir regulon expression in Agrobacterium tumefaciens involves both chromosome- and Ti-plasmid-encoded gene products. We have isolated and characterized a new chromosomal gene that when mutated results in a 2- to 10-fold reduction in the induced expression of vir genes by acetosyringone. This reduced expression occurs in AB minimal medium (pH 5.5) containing either sucrose or glucose and containing phosphate at high or low concentrations. The locus was cloned and used to complement A. tumefaciens strains harboring Tn5 insertions in the gene. Sequence analysis of this locus revealed an open reading frame with strong homology to the miaA locus of Escherichia coli and the mod5 locus of Saccharomyces cerevisiae. These genes encode tRNA: isopentenyltransferase enzymes responsible for the specific modification of the A-37 residue in UNN codon tRNA species. The function of the homologous gene in A. tumefaciens was proven by genetic complementation of E. coli miaA mutant strains. tRNA undermodification in A. tumefaciens miaA mutant strains may reduce vir gene expression by causing a reduced translation efficiency. A slight reduction in the virulence of these mutant Agrobacterium strains on red potato plants, but not on tobacco, tomato, kalanchoe, or sunflower plants, was observed. PMID- 1735706 TI - Role of alternative promoter elements in transcription from the nar promoter of Escherichia coli. AB - The effects of mutations in the -10, -35, and Fnr box regions of the narGHJI promoter of Escherichia coli were determined by assaying the expression of beta galactosidase from narG::lacZ fusion plasmids under aerobic and anaerobic conditions. A 1-base change in the -10 hexamer completely abolished expression, whereas a 3-base change to create the consensus TATAAT resulted in significant aerobic as well as anaerobic expression. A mutation in the putative -35 hexamer did not affect anaerobic expression but reduced aerobic expression from the construction with the -10 consensus sequence. A mutation in the Fnr box severely reduced anaerobic expression but did not affect aerobic expression. When the complete 5' region of the nar operon including the NarL box was present, nitrate stimulated both aerobic and anaerobic expression. Stimulation of expression by nitrate occurred in an fnr mutant but not in a narL mutant. We conclude that the rate of transcription of the nar operon is dependent on two distinct modes of transcription. One mode, which occurs at low levels, depends on the -10 and -35 hexamer sequences and is dramatically enhanced by changing the -10 sequence to the consensus TATAAT. The second depends on the -10 and Fnr box sequences but is independent of the -35 sequence. This second mode occurs at a very high level under anaerobic conditions when Fnr is activated and is also enhanced by changing the -10 sequence to the consensus TATAAT. NarL, activated by nitrate, stimulated both modes of transcription, indicating that it does not act through Fnr but that it directly affects the interaction of RNA polymerase with the promoter. PMID- 1735707 TI - A self-transmissible, narrow-host-range endogenous plasmid of Rhodobacter sphaeroides 2.4.1: physical structure, incompatibility determinants, origin of replication, and transfer functions. AB - Rhodobacter sphaeroides 2.4.1 naturally harbors five cryptic endogenous plasmids (C. S. Fornari, M. Watkins, and S. Kaplan, Plasmid 11:39-47, 1984). The smallest plasmid (pRS241e), with a molecular size of 42 kb, was observed to be a self transmissible plasmid which can transfer only to certain strains of R. sphaeroides. Transfer frequencies can be as high as 10(-2) to 10(-3) per donor under optimal mating conditions in liquid media in the absence of oxygen. pRS241e, designated the S factor, was also shown to possess a narrow host range, failing either to replicate or to be maintained in Escherichia coli, Agrobacterium tumefaciens, and Rhizobium meliloti. It was further revealed that one of the remaining four endogenous plasmids, pRS241d, was also transmissible at a frequency similar to that of the S. factor. As a cointegrate with pSUP203, S was maintained in E. coli, providing sufficient DNA from which a physical map of S could be constructed. Progressive subcloning of S-factor DNA, in conjunction with assays of plasmid transfer, led to the localization and identification of oriV (IncA), IncB, and the putative oriT locus. The DNA sequence of the 427 bp containing oriTs revealed topological similarity to other described oriT sequences, consisting of an A-T-rich DNA region, several direct and inverted repeats, and putative integration host factor (IHF)-binding sites, and was shown to be functional in promoting plasmid transfer. PMID- 1735708 TI - Chromosome transfer in Rhodobacter sphaeroides: Hfr formation and genetic evidence for two unique circular chromosomes. AB - A 600-bp oriT-containing DNA fragment from the Rhodobacter sphaeroides 2.4.1 S factor (oriTs) (A. Suwanto and S. Kaplan, J. Bacteriol. 174:1124-1134, 1992) was shown to promote polarized chromosomal transfer when provided in cis. A Kmr-oriTs sacR-sacB (KTS) DNA cassette was constructed by inserting oriTs-sacR-sacB into a pUTmini-Tn5 Km1 derivative. With this delivery system, KTS appeared to be randomly inserted into the genome of R. sphaeroides, generating mutant strains which also gained the ability to act as Hfr donors. An AseI site in the Kmr cartridge (from Tn903) and DraI and SnaBI sites in sacR-sacB (the levansucrase gene from Bacillus subtilis) were employed to localize the KTS insertion definitively by pulsed-field gel electrophoresis. The orientation of oriTs at the site of insertion was determined by Southern hybridization analysis. Interrupted mating experiments performed with some of the Hfr strains exhibited a gradient of marker transfer and further provided genetic evidence for the circularity and presence of two chromosomal linkage groups in this bacterium. The genetic and environmental conditions for optimized mating between R. sphaeroides strains were also defined. The results presented here and our physical map of the R. sphaeroides 2.4.1 genome are discussed in light of the presence of two chromosomes. PMID- 1735709 TI - cis-acting regulatory elements involved in oxygen and light control of puc operon transcription in Rhodobacter sphaeroides. AB - Transcriptional expression of the puc operon in Rhodobacter sphaeroides is highly regulated by both oxygen and light. The approximately 600 bp of DNA upstream of the 5' ends of the two puc-specific transcripts encompasses two functionally separable cis-acting domains. The upstream regulatory region (URS) (-629 to -150) is responsible for enhanced transcriptional regulation of puc operon expression by oxygen and light. The more proximal upstream region (downstream regulatory region [DRS]), containing putative promoter(s), operator(s), and factor binding sites (-150 to -1), is involved in unenhanced transcriptional expression of the puc operon under aerobic and anaerobic conditions. Thus, the DRS shows normal derepression of puc operon expression when cells are shifted from aerobic to photosynthetic growth conditions in terms of percent change but does not show the potential range of expression that is only observed when elements of the URS are present. Because of these observations, we have made a distinction between anaerobic control (describing the shift) and oxygen control (describing the magnitude of derepression). Promoter(s) and/or activator function(s) of the puc operon is associated with a 35-bp DNA region between -92 and -57. Homologous sequences at -10 to -27 and -35 to -52 appear to involve additional regulatory elements: mutations at -12 (A to C) and -26 (G to A) result in partial derepression of puc operon expression under conditions of high aeration. Both point mutations require the upstream regulatory region (-629 to -150) to be present in cis for partial derepression of puc operon transcription under aerobic conditions. Immediately upstream of the promoter and/or activator region are overlapping consensus sequences for IHF (integratin host factor) and FNR (fumarate nitrate reductase) (-105 to -129). This region appears to be essential for enhanced expression of the puc operon. Thus, these two regulatory domains (URS and DRS) appear to involve approximately seven unique regulatory elements. In addition, the data reveal a direct interaction between the URS (-629 to -150) and the DRS (-150 to -1). PMID- 1735710 TI - Isolation and characterization of trans-acting mutations involved in oxygen regulation of puc operon transcription in Rhodobacter sphaeroides. AB - Transcriptional expression of the puc operon in Rhodobacter sphaeroides 2.4.1 is dependent on the partial pressure of oxygen. By using transcriptional fusions in trans of a promoterless fragment derived from the aminoglycoside-3' phosphotransferase gene of Tn903 to puc operon-specific DNA containing a 629-bp 5' cis-acting regulatory region involved in the expression of puc-specific mRNA, we selected Kmr colonies under aerobic conditions. Two broad classes of mutations, trans and cis, which are involved in O2 control of puc operon transcription, fall into several distinct phenotypic classes. The cis-acting regulatory mutations are characterized in detail elsewhere (J.K. Lee and S. Kaplan, J. Bacteriol. 174:1146-1157, 1992). Two trans-acting regulatory mutants, CL1a and T1a, which are B800-850- Car- and apparently B875-, respectively, were shown to derepress puc operon transcription in the presence of oxygen. The mutation giving rise to CL1a has been shown to act at the puc operon-specific cis acting upstream regulatory region (-629 to -92). On the other hand, the mutation giving rise to T1a, identifying a second trans-acting regulatory factor(s), appears to act at both the upstream (-629 to -92) and the downstream (-92 to -1) regulatory regions of the puc operon as well as at the level(s) of bacteriochlorophyll and carotenoid biosyntheses, as revealed by the presence of the B800-850 complex under chemoheterotrophic growth conditions. Both the B800 850- Car- phenotype and the trans-acting effect on puc operon expression in mutant CL1a were complemented with a 2.2-kb DNA fragment located within the carotenoid gene cluster. Mutant T1a was complemented with a 7.0-kb EcoRI restriction fragment containing the puhA gene and its flanking DNA (6.3 kb) to restore expression of the B875 complex and to suppress the trans-acting effect resulting in the loss of 02 control. Under chemoheterotrophic conditions, mutant T1a was highly unstable, segregating into a PS- mutant designated T4. PMID- 1735711 TI - Purification and characterization of a two-component monooxygenase that hydroxylates nitrilotriacetate from "Chelatobacter" strain ATCC 29600. AB - An assay based on the consumption of nitrilotriacetate (NTA) was developed to measure the activity of NTA monooxygenase (NTA-Mo) in cell extracts of "Chelatobacter" strain ATCC 29600 and to purify a functional, NTA-hydroxylating enzyme complex. The complex consisted of two components that easily dissociated during purification and upon dilution. Both components were purified to more than 95% homogeneity, and it was possible to reconstitute the functional, NTA hydroxylating enzyme complex from pure component A (cA) and component B (cB). cB exhibited NTA-stimulated NADH oxidation but was unable to hydroxylate NTA. It had a native molecular mass of 88 kDa and contained flavin mononucleotide (FMN). cA had a native molecular mass of 99 kDa. No catalytic activity has yet been shown for cA alone. Under unfavorable conditions, NADH oxidation was partly or completely uncoupled from hydroxylation, resulting in the formation of H2O2. Optimum hydroxylating activity was found to be dependent on the molar ratio of the two components, the absolute concentration of the enzyme complex, and the presence of FMN. Uncoupling of the reaction was favored in the presence of high salt concentrations and in the presence of flavin adenine dinucleotide. The NTA Mo complex was sensitive to sulfhydryl reagents, but inhibition was reversible by addition of excess dithiothreitol. The Km values for Mg(2+)-NTA, FMN, and NADH were determined as 0.5 mM, 1.3 microM, and 0.35 mM, respectively. Of 26 tested compounds, NTA was the only substrate for NTA-Mo. PMID- 1735712 TI - The Agrobacterium tumefaciens vir gene transcriptional activator virG is transcriptionally induced by acid pH and other stress stimuli. AB - A set of Agrobacterium tumefaciens operons required for pathogenesis is coordinately induced during plant infection by the VirA and VirG proteins. The intracellular concentration of VirG increases in response to acidic media, and this response was proposed to be regulated at the level of transcription at a promoter (P2) that resembles the Escherichia coli heat shock promoters. To test this hypothesis, we first constructed a virG-lacZ transcriptional fusion. A strain containing this fusion had higher levels of beta-galactosidase activity in acidic media than in media at neutral pH. Second, primer extension analysis of virG indicated that acidic media stimulated the transcription of this promoter. To determine whether P2 is a member of a heat shock-like regulon in A. tumefaciens, five agents that induce E. coli heat shock genes were tested for their abilities to induce a P2-lacZ fusion in A. tumefaciens. P2 was most strongly induced by low pH, was moderately stimulated by CdCl2 or mitomycin C, and was slightly induced by P2 as measured by beta-galactosidase activity and primer extension analysis. Induction by these treatments did not require any Ti plasmid-encoded function or the chromosomally encoded RecA protein. We also pulse labeled cellular proteins after a shift to low pH and detected several proteins whose synthesis was induced by these conditions. We conclude that P2 is primarily induced by acid pH and secondarily by certain other stimuli, each of which is stressful to cell growth. This stress induction is at least partly independent of the heat shock and SOS responses. PMID- 1735713 TI - Restriction endonuclease mapping of the HI2 incompatibility group plasmid R478. AB - A restriction map of the 272-kb IncHI2 plasmid R478 was constructed by using the enzymes ApaI, XbaI, SalI, and XhoI. The map was derived from cloned restriction fragments from R478 inserted into cosmid and plasmid vectors as well as from double-digestion analysis of R478 and R478 miniplasmids. All previously known resistance determinants were cloned from R478, and their positions were located on the restriction map. A region involved in incompatibility was cloned and mapped. The location of a previously unreported arsenite resistance gene was also determined. The genes encoding tellurite resistance, colicin B resistance, and phage inhibition were found to be associated with a 6.7-kb SalI fragment of R478. PMID- 1735714 TI - Cloning and sequence analysis of the Chlamydia trachomatis spc ribosomal protein gene cluster. AB - We identified and sequenced a segment of Chlamydia trachomatis chromosomal DNA that shows homology to the Escherichia coli spc and distal region of the S10 ribosomal protein (r-protein) operons. Its sequence revealed a high degree of nucleotide and operon context conservation with the E. coli r-protein genes. The C. trachomatis spec operon contains the r-protein genes for L14, L24, L5, S8, L6, L18, S5, L15, and Sec Y along with the genes for r-proteins L16, L29, and S17 of the S10 operon. The two operons are separated by a 16-bp intragenic region which contains no transcription signals. However, a putative promoter for the transcription of the spc operon was found 162 nucleotides upstream of the CtrL14e start site; it revealed significant homology to the E. coli consensus promoter sequences. Interestingly, our results indicate the absence of any structure resembling an EcoS8 regulatory target site on C. trachomatis spc mRNA in spite of significant amino acid identity between E. coli and C. trachomatis r-proteins. Also, the intrinsic aminoglycoside resistance in C. trachomatis is unlikely to be mediated by CtrL6e since E. coli expressing CtrL6e remained susceptible to gentamicin (MIC less than 0.5 micrograms/ml). PMID- 1735715 TI - Mutagenesis of ribosomal protein S8 from Escherichia coli: defects in regulation of the spc operon. AB - The structural features of Escherichia coli ribosomal protein S8 that are involved in translational regulation of spc operon expression and, therefore, in its interaction with RNA have been investigated by use of a genetic approach. The rpsH gene, which encodes protein S8, was first inserted into an expression vector under the control of the lac promoter and subsequently mutagenized with methoxylamine or nitrous acid. A screening procedure based on the regulatory role of S8 was used to identify mutants that were potentially defective in their ability to associate with spc operon mRNA and, by inference, 16S mRNA. In this way, we isolated 39 variants of the S8 gene containing alterations at 34 different sites, including 37 that led to single amino acid substitutions and 2 that generated premature termination codons. As the mutations were distributed throughout the polypeptide chain, our results indicate that amino acid residues important for the structural integrity of the RNA-binding domain are not localized to a single segment. Nonetheless, the majority were located within three short sequences at the N terminus, middle, and C terminus that are phylogenetically conserved among all known eubacterial and chloroplast versions of this protein. We conclude that these sites encompass the main structural determinants required for the interaction of protein S8 with RNA. PMID- 1735716 TI - Reattachment of surface array proteins to Campylobacter fetus cells. AB - Campylobacter fetus strains may be of serotype A or B, a property associated with lipopolysaccharide (LPS) structure. Wild-type C. fetus strains contain surface array proteins (S-layer proteins) that may be extracted in water and that are critical for virulence. To explore the relationship of S-layer proteins to other surface components, we reattached S-layer proteins onto S- template cells generated by spontaneous mutation or by serial extractions of S+ cells with water. Reattachment occurred in the presence of divalent (Ba2+, Ca2+, Co2+, and Mg2+) but not monovalent (H+, NH4+, Na+, K+) or trivalent (Fe3+) cations. The 98 , 125-, 127-, and 149-kDa S-layer proteins isolated from strains containing type A LPS (type A S-layer protein) all reattached to S- template cells containing type A LPS (type A cells) but not to type B cells. The 98-kDa type B S-layer protein reattached to SAP- type B cells but not to type A cells. Recombinant 98 kDa type A S-layer protein and its truncated amino-terminal 65- and 50-kDa segments expressed in Escherichia coli retained the full and specific determinants for attachment. S-layer protein and purified homologous but not heterologous LPS in the presence of calcium produced insoluble complexes. By quantitative enzyme-linked immunosorbent assay, the S-layer protein copy number per C. fetus cell was determined to be approximately 10(5). In conclusion, C. fetus cells are encapsulated by a large number of S-layer protein molecules which may be specifically attached through the N-terminal half of the molecule to LPS in the presence of divalent cations. PMID- 1735717 TI - DNA sequences and characterization of dtxR alleles from Corynebacterium diphtheriae PW8(-), 1030(-), and C7hm723(-). AB - The structural gene encoding DtxR, an iron-dependent diphtheria tox regulatory element, has recently been cloned and sequenced from the C7(-) strain of Corynebacterium diphtheriae (J. M. Boyd, M. Oza, and J. R. Murphy, Proc. Natl. Acad. Sci. USA 87:5972, 1990). We report here the molecular cloning, DNA sequence analysis, and characterization of DtxR from the PW8(-), 1030(-), and C7hm723 strains of C. diphtheriae. While the sequence of dtxR from PW8(-) is identical to that of the C7(-) allele, the sequence of dtxR from the 1030(-) strain is only 91.4% identical; however, the deduced amino acid sequence of DtxR from 1030(-) differs by only 6 of 678 amino acids. Moreover, DtxR from all three strains is shown to regulate expression of beta-galactosidase from a tox promoter-operator (toxPO)-lacZ transcriptional fusion. In contrast, the dtxR allele from the iron insensitive tox constitutive mutant C7hm723 was found to have a single G----A transition, resulting in a substitution of Arg-47 to His and the loss of tox regulatory activity in recombinant Escherichia coli. PMID- 1735718 TI - Mutual adjustment of glucose uptake and metabolism in Trypanosoma brucei grown in a chemostat. AB - The mutual adjustment of glucose uptake and metabolism in the insect stage of the protozoan parasite Trypanosoma brucei was studied. T. brucei was preadapted in the chemostat to conditions in which either glucose or proline served as the major carbon and energy source. Cells were grown and adapted to either energy or non-energy limitation at a low dilution rate (0.5 day-1) or a high dilution rate (1 day-1). The cells were then used in short- to medium-term uptake experiments with D-[14C]glucose as a tracer. In time course experiments a steady state was reached after 15 min regardless of the preadaptation conditions. This steady state level increased with increasing glucose availability during preadaptation. The rate of glucose uptake and the hexokinase activity were linearly correlated. In short-term 5- to 90-s) uptake experiments a high transport rate was measured with cultures grown in excess glucose, an intermediate rate was measured with proline-grown cultures, and a low rate was measured in organisms grown under glucose limitation. Glucose metabolism and proline metabolism did not affect each other during the 15-min incubations. Glucose uptake, as a function of the external glucose concentration, did not obey simple Michaelis-Menten kinetics but could be described by a two-step mechanism: (i) transport of glucose by facilitated diffusion and (ii) subsequent metabolism of glucose. The respective rates of the two steps were adjusted to each other. It is concluded that T. brucei is capable of adjusting the different metabolic processes in a way that gives maximum energy efficiency at the cost of short-term flexibility. PMID- 1735719 TI - Expression of bacterial mercuric ion reductase in Saccharomyces cerevisiae. AB - The gene merA coding for bacterial mercuric ion reductase was cloned under the control of the yeast promoter for alcohol dehydrogenase I in the yeast Escherichia coli shuttle plasmid pADH040-2 and transformed into Saccharomyces cerevisiae AH22. The resulting transformant harbored stable copies of the merA containing hybrid plasmid, displayed a fivefold increase in the MIC of mercuric chloride, and synthesized mercuric ion reductase activity. PMID- 1735720 TI - Transcriptional activation of the Listeria monocytogenes hemolysin gene in Bacillus subtilis. AB - The prfA gene of Listeria monocytogenes was recently reported to be required for expression of hly, which encodes a pore-forming hemolysin essential for pathogenicity (M. Leimeister-Wachter, C. Haffner, E. Domann, W. Goebel, and T. Chakraborty, Proc. Natl. Acad. Sci. USA 87:8336-8340, 1990). We demonstrate here that a hly-lacZ fusion introduced into Bacillus subtilis is strongly activated when the prfA gene product is supplied in trans under the control of an isopropyl beta-D-thiogalactopyranoside-inducible promoter, Pspac. Moreover, the PrfA dependent activation of hly is abolished by point mutations in a 14-bp DNA palindromic sequence present in the 5' upstream region of hly. This indicates that PrfA is both necessary and sufficient for hly transcriptional activation and establishes the palindrome as the likely target sequence for PrfA interaction. The presence of a palindrome in the upstream regions of three additional L. monocytogenes genes clustered near hly suggests that PrfA may serve as a transcriptional activator for a major virulence regulon of L. monocytogenes. In addition, the ability of PrfA to activate its target promoters effectively in B. subtilis suggests that further analysis of this regulon and perhaps other aspects of L. monocytogenes gene regulation might be carried out in part through reconstruction experiments in B. subtilis. PMID- 1735721 TI - Analysis of the Bacillus subtilis tyrS gene: conservation of a regulatory sequence in multiple tRNA synthetase genes. AB - The Bacillus subtilis tyrS gene, which encodes tyrosyl-tRNA synthetase (TyrTS), was isolated, and its nucleotide sequence was determined. The cloned gene was shown to complement an Escherichia coli tyrS (Ts) mutant. The predicted amino acid sequence exhibited 70% identity to that of Bacillus stearothermophilus TyrTS and 55% identity to that of E. coli TyrTS, while identity to a second cryptic B. subtilis TyrTS gene, designated tyrZ, was only 27%. Primer extension analysis indicated that tyrS transcription initiated at a vegetative promoter sequence located 300 nucleotides upstream of the AUG start codon. The mRNA leader region was found to contain an inverted repeat sequence resembling a transcriptional terminator. Expression of a transcriptional tyrS-lacZ fusion was found to be induced by starvation for tyrosine in a tyrosine auxotroph (tyrA1). Transcription initiation was unaffected by tyrosine starvation. Deletion of the terminator region in a tyrS-lacZ fusion resulted in high-level constitutive expression. Immediately preceding the putative terminator was sequence element found to be conserved in the upstream region of a number of Bacillus tRNA synthetase genes as well as in the ilv-leu biosynthetic operon; mutation of this element in tyrS resulted in low-level uninducible expression. The conservation of this sequence element suggests that aminoacyl-tRNA synthetase genes and the ilv-leu operon may be regulated by a common mechanism in Bacillus spp. PMID- 1735722 TI - Malate dehydrogenase from Chlorobium vibrioforme, Chlorobium tepidum, and Heliobacterium gestii: purification, characterization, and investigation of dinucleotide binding by dehydrogenases by use of empirical methods of protein sequence analysis. AB - Malate dehydrogenase (MDH; EC 1.1.1.37) from strain NCIB 8327 of the green sulfur bacterium Chlorobium vibrioforme was purified to homogeneity by triazine dye affinity chromatography followed by gel filtration. Purification of MDH gave an approximately 1,000-fold increase in specific activity and recoveries of typically 15 to 20%. The criteria of purity were single bands on sodium dodecyl sulfate (SDS) and nondenaturing polyacrylamide electrophoresis (PAGE) and the detection of a single N terminus in an Edman degradation analysis. MDH activity was detected in purified preparations by activity staining of gels in the direction of malate oxidation. PAGE and gel filtration (Sephadex G-100) analyses showed the native enzyme to be a dimer composed of identical subunits both at room temperature and at 4 degrees C. The molecular weight of the native enzyme as estimated by gel filtration was 77,000 and by gradient PAGE was 74,000. The subunit molecular weight as estimated by SDS-gradient PAGE was 37,500. N-terminal sequences of MDHs from C. vibrioforme, Chlorobium tepidum, and Heliobacterium gestii are presented. There are obvious key sequence similarities in MDHs from the phototrophic green bacteria. The sequences presented probably possess a stretch of amino acids involved in dinucleotide binding which is similar to that of Chloroflexus aurantiacus MDH and other classes of dehydrogenase enzymes but unique among MDHs. PMID- 1735723 TI - Role of the two-component leader sequence and mature amino acid sequences in extracellular export of endoglucanase EGL from Pseudomonas solanacearum. AB - The egl gene of Pseudomonas solanacearum encodes a 43-kDa extracellular endoglucanase (mEGL) involved in wilt disease caused by this phytopathogen. Egl is initially translated with a 45-residue, two-part leader sequence. The first 19 residues are apparently removed by signal peptidase II during export of Egl across the inner membrane (IM); the remaining residues of the leader sequence (modified with palmitate) are removed during export across the outer membrane (OM). Localization of Egl-PhoA fusion proteins showed that the first 26 residues of the Egl leader sequence are required and sufficient to direct lipid modification, processing, and export of Egl or PhoA across the IM but not the OM. Fusions of the complete 45-residue leader sequence or of the leader and increasing portions of mEgl sequences to PhoA did not cause its export across the OM. In-frame deletion of portions of mEGL-coding sequences blocked export of the truncated polypeptides across the OM without affecting export across the IM. These results indicate that the first part of the leader sequence functions independently to direct export of Egl across the IM while the second part and sequences and structures in mEGL are involved in export across the OM. Computer analysis of the mEgl amino acid sequence obtained from its nucleotide sequence identified a region of mEGL similar in amino acid sequence to regions in other prokaryotic endoglucanases. PMID- 1735724 TI - Compositional analysis of Helicobacter pylori rough-form lipopolysaccharides. AB - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze the macromolecular heterogeneity of lipopolysaccharides (LPS) from seven fresh clinical isolates and three culture collection strains of the human pathogen Helicobacter pylori. All the clinical isolates produced smooth-form LPS with O side chains of relatively homogeneous chain length, whereas the culture collection strains yielded rough-form LPS. A better yield of the latter LPS was obtained when combined protease pretreatment and hot phenol-water extraction were used than when the conventional phenol-water technique alone was used for extraction. The LPS of the three culture collection strains (S-24, C-5437, and NCTC 11637) were chemically characterized. Constituents common to all the LPS were fucose, D-mannose, D-glucose, D-galactose, D-glycero-D-manno-heptose, L glycero-D-manno-heptose, and 3-deoxy-D-manno-2-octulosonic acid. The molar ratios of the hexoses differed between different strains, thereby reflecting structural differences. Phosphate, phosphorylethanolamine, and pyrophosphorylethanolamine were present also. Free lipid A contained D-glucosamine and fatty acids, with phosphate and a minor amount of ethanolamine. The major fatty acids were ester- and amide-bound 3-hydroxyoctadecanoic acid and ester-bound octadecanioc and 3 hydroxyhexadecanoic acids, with minor amounts of ester-bound tetradecanoic and hexadecanoic acids. In addition to the uncommonly long 3-hydroxy fatty acids, an unusual phosphorylation pattern was deduced to be present in the lipid A. PMID- 1735725 TI - Identification and analysis of the genes coding for the putative pyruvate dehydrogenase enzyme complex in Acholeplasma laidlawii. AB - A monospecific antibody recognizing two membrane proteins in Acholeplasma laidlawii identified a plasmid clone from a genomic library. The nucleotide sequence of the 4.6-kbp insert contained four sequential genes coding for proteins of 39 kDa (E1 alpha, N terminus not cloned), 36 kDa (E1 beta), 57 kDa (E2), and 36 kDa (E3; C terminus not cloned). The N termini of the cloned E2, E1 beta, and native A. laidlawii E2 proteins were verified by amino acid sequencing. Computer-aided searches showed that the translated DNA sequences were homologous to the four subenzymes of the pyruvate dehydrogenase complexes from gram-positive bacteria and humans. The plasmid-encoded 57-kDa (E2) protein was recognized by antibodies against the E2 subenzymes of the pyruvate and oxoglutarate dehydrogenase complexes from Bacillus subtilis. A substantial fraction of the E2 protein as well as part of the pyruvate dehydrogenase enzymatic activity was associated with the cytoplasmic membrane in A. laidlawii. In vivo complementation with three different Escherichia coli pyruvate dehydrogenase-defective mutants showed that the four plasmid-encoded proteins were able to restore pyruvate dehydrogenase enzyme activity in E. coli. Since A. laidlawii lacks oxoglutarate dehydrogenase and most likely branched-chain dehydrogenase enzyme complex activities, these results strongly suggest that the sequenced genes code for the pyruvate dehydrogenase complex. PMID- 1735726 TI - Cloning and sequencing of the gene coding for alcohol dehydrogenase of Bacillus stearothermophilus and rational shift of the optimum pH. AB - Using Bacillus subtilis as a host and pTB524 as a vector plasmid, we cloned the thermostable alcohol dehydrogenase (ADH-T) gene (adhT) from Bacillus stearothermophilus NCA1503 and determined its nucleotide sequence. The deduced amino acid sequence (337 amino acids) was compared with the sequences of ADHs from four different origins. The amino acid residues responsible for the catalytic activity of horse liver ADH had been clarified on the basis of three dimensional structure. Since those catalytic amino acid residues were fairly conserved in ADH-T and other ADHs, ADH-T was inferred to have basically the same proton release system as horse liver ADH. The putative proton release system of ADH-T was elucidated by introducing point mutations at the catalytic amino acid residues, Cys-38 (cysteine at position 38), Thr-40, and His-43, with site directed mutagenesis. The mutant enzyme Thr-40-Ser (Thr-40 was replaced by serine) showed a little lower level of activity than wild-type ADH-T did. The result indicates that the OH group of serine instead of threonine can also be used for the catalytic activity. To change the pKa value of the putative system, His-43 was replaced by the more basic amino acid arginine. As a result, the optimum pH of the mutant enzyme His-43-Arg was shifted from 7.8 (wild-type enzyme) to 9.0. His-43-Arg exhibited a higher level of activity than wild-type enzyme at the optimum pH. PMID- 1735727 TI - Characterization and comparison of Clostridium cellulovorans endoglucanases xylanases EngB and EngD hyperexpressed in Escherichia coli. AB - By the use of a T7 expression system, endoglucanases-xylanases EngB and EngD from Clostridium cellulovorans were hyperexpressed and purified from Escherichia coli. The two enzymes demonstrated both endoglucanase and xylanase activities. The substrate specificities of both endoglucanases were similar except that EngD had four-times-greater p-nitrophenyl beta-1,4-cellobiosidase activity. The two proteins were very homologous (80%) up to the Pro-Thr-Thr region which divided the protein into -NH2- and -COOH-terminals. The -COOH- region of EngB has high homology to the endoglucanases and a xylanase from Clostridium thermocellum and to an endoglucanase from Clostridium cellulolyticum and did not show strong binding to cellulose (Avicel). However, the -COOH- region of EngD, which had homology to the cellulose-binding domains of Cellulomonas fimi exo- and endoglucanases and to Pseudomonas fluorescens endoglucanase, demonstrated binding ability to cellulose even when the domain was fused to the N-terminal domain of EngB. By probing the Avicel-purified cellulase complex (F8) with anti-EngB and anti-EngD antibodies, both EngB and EngD were shown to be present on the cellulase complex of C. cellulovorans. Many proteins homologous to EngB and EngD were also present on the complex. PMID- 1735728 TI - The subtilin gene of Bacillus subtilis ATCC 6633 is encoded in an operon that contains a homolog of the hemolysin B transport protein. AB - Sequence analysis upstream from the subtilin structural gene (spaS) in Bacillus subtilis ATCC 6633 revealed several open reading frames, SpaB, SpaC, and SpaD. SpaB, consisting of 599 amino acid residues, shows excellent homology with a variety of membrane translocator proteins, such as HlyB from Escherichia coli and some mammalian multidrug resistance proteins. When the spaB gene was interrupted by integration of a chloramphenicol acetyltransferase gene, the ability of the cell to produce subtilin, as determined by a halo assay, was lost. The homology of SpaB to translocator proteins, including transmembrane and ATP-binding regions, suggests that SpaB may play a role in subtilin secretion. The SpaB open reading frame overlaps with another open reading frame called SpaC, and the possibility that the SpaB and SpaC proteins become fused by frameshifting is considered. Regions of homology between SpaD (177 residues) and HlyD were also found, suggesting that SpaD may participate with SpaB in translocation of subtilin through the membrane. Although no readily interpretable homologies to SpaC (442 residues) were found, its sequence suggests that it is membrane associated. The absence of rho-independent transcription terminators between these open reading frames suggests that they are all part of the same operon. PMID- 1735729 TI - Design of temperature-sensitive penicillinase repressors by replacement of Pro in predicted beta-turn structures. AB - Pro residues in predicted beta-turn structures were substituted with other amino acids to obtain temperature-sensitive penicillinase repressors (PenI). A mutant repressor (P70L; Pro-70 is substituted with Leu) was inactive at 48 degrees C and penP gene expression was derepressed (1,200 U/OD660 [optical density at 660 nm] ), although the mutant was still active at 30 degrees C (27 U). The heat induction ratio (penicillinase activity at 48 degrees C compared with that at 30 degrees C) of the mutant was 98 times higher than that of the wild type (i.e., 44 versus 0.45). This result indicated that the side chain of the Leu residue in P70L destroyed the proper folding of the repressor protein at the elevated temperature, whereas the Pro residue of the wild-type repressor stabilized this predicted beta-turn structure even at 48 degrees C. When the Pro residue was replaced by amino acid residues with smaller side chains (i.e., Gly and Ala), these mutant repressors were less temperature sensitive than P70L. These data suggest that the presence of the Pro residue in the beta-turn structure could be one of the key factors in stabilizing protein structure at elevated temperatures. PMID- 1735730 TI - The central domain of Rhizobium leguminosarum DctD functions independently to activate transcription. AB - Sigma 54-dependent transcriptional activators such as Escherichia coli NtrC, Rhizobium meliloti NifA, and Rhizobium leguminosarum DctD share similar central and carboxy-terminal domains but differ in the structure and function of their amino-terminal domains. We have deleted the amino-terminal and carboxy-terminal domains of R. leguminosarum DctD and have demonstrated that the central domain of DctD, like that of NifA, is transcriptionally competent. PMID- 1735731 TI - Expression of the proliferation-associated Ki-67 antigen of transferrin receptors and of DNA polymerase alpha in human tumour lines: implications for in vitro chemoresistance. AB - To compare the time course of in vitro expression of various proliferation associated markers including Ki-67 antigen, transferrin receptors (TfR), and DNA polymerase alpha, six human tumour cell lines of different histological origin were studied under defined conditions. Proliferation markers were demonstrated by peroxidase/anti-peroxidase staining using specific monoclonal antibodies, and their expression was compared to results obtained from [3H]-thymidine incorporation assays and cell counting. Expression of all proliferation markers began to increase during the lag phase, and occurred earlier than elevations of [3H]dT incorporation and cell numbers were recorded. Maximum expression was observed before cell growth reached plateau phase. The time courses of expression of DNA polymerase and Ki-67 were almost identical. The closest correlation of [3H]dT incorporation with time course of expression of proliferation-associated markers was observed, when intranuclear staining of DNA polymerase was analysed. TfR were expressed earlier than the polymerase and Ki-67. Since TfR were also found at remarkable levels in resting cells, they seem less proliferation specific than Ki-67 and DNA polymerase. While in rapidly growing cell lines more than 95% of the cells expressed Ki-67, TfR, and more than 75% DNA polymerase in cell nuclei, a malignant melanoma and a pleural mesothelioma line displayed fewer than 35% of cells stained for DNA polymerase in cell nuclei during log phase. Determination of growth fractions by monoclonal antibodies may thus contribute to the prediction of chemoresistance by identifying quiescent cells that are not sensitive to S-phase-specific drugs. PMID- 1735733 TI - Local hyperthermia enhances cyclophosphamide, ifosfamide and cis diamminedichloroplatinum cytotoxicity on human-derived breast carcinoma and sarcoma xenografts in nude mice. AB - Antitumour response and toxicity of locally applied hyperthermia with or without cyclophosphamide, ifosfamide, and cis-diamminedichloroplatinum (cisplatin) have been compared. The model systems were human breast carcinoma (MX1/3) and human sarcoma (S117) grown in nude mice. In order to detect changes of tumour oxygenation intratumoral PO2 and pH were measured before, during and following hyperthermia. In both human tumour lines a monotherapy with one of the cytotoxic drugs or with hyperthermia caused a transient growth delay, while the combination of the same dose of the drugs with hyperthermia (at 43 degrees C for 1 h) resulted in complete tumour remissions. During hyperthermia, in both tumour types oxygenation was improved. Intratumoral pH remained practically unchanged. PMID- 1735732 TI - Effect of a bovine hemoglobin preparation on the response of the FSaIIC fibrosarcoma to chemotherapeutic alkylating agents. AB - Polymerized bovine hemoglobin solutions (PBHS) are being actively investigated as blood substitutes. In studies analogous to those we conducted with perfluorochemical emulsions/carbogen, we have examined the effect of PBHS +/- carbogen (95% O2, 5% CO2) breathing on the antitumor efficacy of melphalan, cyclophosphamide, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) and cis diamminedichloroplatinum(II) (cis-platin). The tumor growth delay of the FSaIIC fibrosarcoma treated with melphalan (10 mg/kg), cyclophosphamide (150 mg/kg), cisplatin (10 mg/kg) and BCNU (15 mg/kg) was increased about 2.2-fold, about 2.1 fold, about 1.2-fold and about 1.5-fold, respectively, when PBHS (12 mg/kg) was administered i.v. before each drug was injected i.p. The tumor growth delay produced by each drug was further increased when carbogen breathing for 6 h was allowed after administration of the drug and PBHS. In tumor cell survival experiments 24 h following drug treatment, the addition of PBHS increased the tumor cell killing of both melphalan and cyclophosphamide by about a factor of 10 at the lowest doses of each drug tested (10 mg/kg for melphalan and 100 mg/kg for cyclophosphamide) compared to the drug alone. However, at higher drug doses this effect was lost. The toxicity of each antitumor agent toward bone marrow (granulocyte/macrophage-colony-forming units) was increased 2- to 3-fold by the combined treatment. These results suggest that use of PBHS +/- carbogen breathing may add significantly to the efficacy of antitumor alkylating agents, however, the in vivo/in vitro data suggest that there will be increased bone marrow toxicity with this approach. This needs to be taken into account in the design of clinical trials. PMID- 1735734 TI - Antitumour and immunological activity of a beta 1----3/1----6 glucan from Glomerella cingulata. AB - The in vivo antitumour activity of a beta 1----3/1----6 glucan from the fungus Glomerella cingulata was investigated in vivo. The glucan exhibited a strong inhibition of tumour growth of the allogeneic Sarcoma-180 as well as the syngeneic DBA/2-MC.SC-1 fibrosarcoma with inhibition ratios up to 100%. Against the hormone sensitive Noble-Nb-R prostate carcinoma the glucan alone showed a moderate antitumour effect, whereas in combination with diethylstilbestrol an almost complete regression of the tumour could be achieved. It could be demonstrated that a highly ordered structure of the glucan is not essential for the antitumour activity. Since the glucan expressed no direct cytotoxic effects, the immunomodulating activity was investigated in vitro in order to get an indication for a possible mode of action. In the lymphocyte transformation assay the glucan at a dose of 100 micrograms/ml caused a fourfold increase in the proliferation of murine spleen lymphocytes. Moreover, the glucan stimulated the phagocytosis of zymosan by bone marrow macrophages up to 100%. However, the glucan was not able to render macrophages cytotoxic against P-815 mastocytoma cells. PMID- 1735735 TI - Tumours induced by Moloney murine sarcoma virus are clonal in rats, not clonal in mice. AB - Moloney murine sarcoma virus (M-MSV) induces rapidly growing tumours in adult mice of most conventional strains. Rats are less susceptible to M-MSV oncogenesis, but the few rhabdomyosarcomas that do develop after viral inoculation of newborn animals closely resemble conventional malignancies: they develop after a long latency, grow progressively, and metastasize to regional lymph nodes and lungs. Southern blot analysis with a v-mos-specific probe of M MSV-induced tumours in both species demonstrated an oligo-, monoclonal pattern of exogenous v-mos integration only in the rat system, while mouse tumours were not clonal in origin. Furthermore, the same type of analysis of lymph node and lung metastases showed that cell clones already present in the primary rat lesion colonized secondary sites during tumour progression. Apparently, Moloney murine leukemia virus (M-MuLV) was not involved in rhabdomyosarcoma pathogenesis since M MuLV-specific DNA sequences could not be demonstrated in three of the six rat tumours. Finally, in all mouse tumours, unintegrated linear M-MSV proviruses could be readily detected. PMID- 1735736 TI - Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy. AB - The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification. PMID- 1735737 TI - Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy. AB - One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure. PMID- 1735738 TI - Does malignant transformation of benign soft-tissue tumours occur? A clinicomorphological study of ten initially misdiagnosed soft-tissue sarcomas. AB - Ten soft-tissue sarcomas out of a consecutive series of 201 neoplasms are described, in which the clinical histories were suggestive of malignant transformation of a benign lesion excised from the same location 2-97 months before. Each of the 10 preceding soft-tissue neoplasms was reviewed histologically and reclassified as either highly (n = 8) or moderately differentiated (n = 2) sarcomas. Irrespective of the primary treatment, these initially misdiagnosed tumours showed an overall better prognosis than the whole group of soft-tissue sarcomas (5- and 10-year survival rates 76% versus 44%, and 52% versus 30% respectively). Their clinical course was, however, characterized by up to 6 (mean 2.9) local recurrences. From the total series of 201 tumours the authors conclude that soft-tissue sarcomas other than malignant schwannomas in the setting of von Recklinghausen's disease only exceptionally, if ever, arise from benign precursors. PMID- 1735739 TI - Theory-based advanced rehabilitation nursing: is it a reality? PMID- 1735740 TI - Rehabilitation: umbrella for health care. PMID- 1735741 TI - Exercise: wellness maintenance for the elderly client. PMID- 1735742 TI - Group support for families during the acute phase of rehabilitation. PMID- 1735743 TI - Community-based rehabilitation. PMID- 1735744 TI - A rehabilitation clinical nurse specialist: evaluation of the role in a home health care setting. PMID- 1735745 TI - Rehabilitation takes to the road. PMID- 1735746 TI - Rehabilitation case managers: ahead of their time. PMID- 1735747 TI - Children with chronic conditions growing up in institutions: issues regarding habilitation. PMID- 1735748 TI - The interdisciplinary team: research and education. PMID- 1735749 TI - Withdrawal symptoms in a postoperative patient. PMID- 1735750 TI - Immunopathogenesis of HIV infection. AB - The early natural history of HIV does not differ markedly from that of other lymphotropic pathogens. However, the HIV lentivirus has a number of unique features that not only facilitate escape from the host immune response but eventually lead to dysfunction and destruction of the immune system. Actual cure will not be possible until a way to eliminate the stored virus is found. PMID- 1735751 TI - Who owns our genes? PMID- 1735752 TI - Anemia in the hospitalized patient. PMID- 1735753 TI - Still a question? PMID- 1735754 TI - Symptoms of low blood pressure. PMID- 1735755 TI - Whither our children? PMID- 1735756 TI - A case of pseudo pseudogout. PMID- 1735757 TI - Cyanotic heart disease in a young woman. PMID- 1735758 TI - Acute abdominal pain in a dialysis patient. PMID- 1735759 TI - Chlamydial disease in women. PMID- 1735760 TI - Current concepts in anticoagulation. AB - Anticoagulation therapy continues to evolve as more precise indications for its use are recognized. With adoption of the international normalized ratio, safer and more effective application is in the offing. Newer uses are discussed. PMID- 1735761 TI - The missing volumes. PMID- 1735763 TI - The shield of invulnerability. PMID- 1735762 TI - Kala-azar: the long anguish of the black sickness. PMID- 1735764 TI - Deficiencies in factors IX and VIII: what is now known. AB - Genetic defects both gross and subtle have recently been identified in about 900 patients with hemophilia A or B. The defects, which include deletions, insertions, and point mutations, reveal much about genetic structure-function relationships in hemophilia. These insights will lead to improved treatment of bleeding disorders and perhaps to their cure. PMID- 1735765 TI - A sterilized woman who did not feel right. PMID- 1735766 TI - Aggressive therapy of acute MI in the elderly. AB - In elderly patients with myocardial infarction, clinicians face a management catch-22: Mortality is increased in the absence of therapy, which is often withheld because elderly patients may succumb to its complications. What to do? Evidence from recent studies suggests that the benefits of aggressive therapy with early thrombolysis may outweigh the risks. PMID- 1735767 TI - Unilateral pulmonary edema. AB - Awareness of pathophysiology and differential diagnosis of this entity is crucial for management. Edema may be ipsilateral or contralateral to the perfusion defect, or may be variable. A variable case is presented. PMID- 1735768 TI - AIDS and alcohol: concerns for the physician. AB - Persons who abuse alcohol have not been specifically targeted for education on prevention of AIDS, yet failure to address the connection between alcohol and HIV transmission may carry a heavy price. PMID- 1735769 TI - Effects of gamma-interferon on major histocompatibility complex antigen expression and lymphocytic infiltration in the 9L gliosarcoma brain tumor model: implications for strategies of immunotherapy. AB - Effects of gamma-interferon (IFN-gamma) on immune parameters in the 9L gliosarcoma model were examined. IFN-gamma increased class I major histocompatibility complex (MHC) expression in 9L cells in vitro. In vivo, intratumor injections of IFN-gamma led to increased numbers of inflammatory cells within the tumor and class II+ mononuclear phagocytes at its periphery, and increased MHC class I or II expression by endothelial and ependymal cells. Class I expression in 9L cells themselves was not increased. This suggests that there may be inhibition of class I induction in vivo for certain cell types, for which immunotherapies based on non-MHC restricted mechanisms may be more effective. PMID- 1735770 TI - Anti-GM1 IgA antibodies in Guillain-Barre syndrome. AB - Serum anti-GM1 IgA antibodies were detected in 15 of 53 (28%) patients with the acute Guillain-Barre syndrome (GBS) and in one of 26 (4%) patients with other neurological diseases. Although nine GBS patients had anti-GM1 IgA titers of 1:200 or less, six patients had titers of 1:800 or more. Some GBS patients with anti-GM1 IgA antibodies also had antibodies against GD1b or GM2 or both. The presence of markedly elevated anti-GM1 IgA was associated with a poor clinical outcome at 6 and 12 months following onset of the GBS. The possible pathogenetic role of anti-GM1 IgA antibodies remains to be established. PMID- 1735771 TI - Intrathecal synthesis of soluble class I antigens in multiple sclerosis. AB - We have studied the intrathecal synthesis of soluble class I antigens (sHLA), reflected by the index IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin), in multiple sclerosis (MS). IH was increased in patients in relapse, but normal in patients in remission; these findings show that there is a high lymphocyte activation within the central nervous system in patients with clinically active MS. PMID- 1735772 TI - Effect of parenteral administration of GM1 on cytokines and anti-ganglioside antibody patterns. Preliminary report in normal human individuals. AB - To assess the effects of monosialoganglioside GM1 on some immunological parameters, 12 healthy men were treated with 100 mg GM1 i.m. daily for 15 days. Before and after treatment, the following were studied: (1) serum levels of antibodies against GM1, asialo-GM1 (aGM1), GM2 and GD1b; (2) serum levels of interleukin (IL)-1 beta, IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma); (3) IL-1 beta and TNF alpha production by peripheral blood monocytes (PBMO). Anti-ganglioside antibody and cytokine serum levels were not affected by exogenous GM1 administration with the exception of a transient increase in anti-GM1 antibody titer observed in one subject. In addition, no inhibition of IL-1 beta and TNF-alpha production by PBMO was observed. These preliminary data do not support a potential immunogenic or immunomodulatory function for in vivo administered GM1. PMID- 1735773 TI - Computer program for planning and evaluating microplate experiments. AB - A microcomputer program is described for planning and statistically evaluating microplate and other similar experiments. This program is written in BASIC and can be run on any PC XT/AT compatible computer under DOS. The first part of the program writes the protocol of the experiment into a disk file and sends it to a printer and also prints specifications for the addition of ingredients. The second part of the program calculates means and standard deviations of the values measured for all groups of samples. It is also possible for the program to calculate activation coefficients, coefficients of modulation and percentages of suppression for special groups. Inputting the required data can be performed manually from the keyboard or automatically from disk files. PMID- 1735774 TI - A quantitative immunoassay using chicken antibodies for detection of native and recombinant alpha-amidating enzyme. AB - A sensitive competitive ELISA has been developed for the detection and quantitation of native and recombinant alpha-amidating enzyme. Chickens immunized with purified enzyme (75 kDa) isolated from a rat medullary thyroid carcinoma, produced IgY antibodies specific for the native enzyme. The assay is defined by a standard curve with a linear range of 0.78-12.5 ng/ml in phosphate-buffered saline, and a limit of sensitivity for detection of the enzyme of 0.20 ng/ml. The immunoassay is capable of detecting enzyme from both tumor derived sources, and from cells genetically engineered to secrete the enzyme into tissue culture medium containing up to 10% fetal calf serum. PMID- 1735775 TI - Propagation of a mouse myeloma cell line J558L producing human CD4 immunoglobulin G1. AB - Transfected mouse myeloma cells are of increasing interest for the production of a wide variety of solubilised recombinant fusion proteins. A stably transfected J558L mouse myeloma subclone (J558L-CD4) secreting human CD4-immunoglobulin type G1 receptor (CD4-H gamma 1) was employed as a model system for cell suspension culture and expression of chimaeric molecules. Cells were grown up to 3-5 x 10(6) cells/ml in serum-free and protein-reduced DHI medium consisting of a mixture of DMEM, HamF12 and IMDM media supplemented with transferrin, insulin, Primatone RL and Pluronic F68. Primatone RL was the essential growth-promoting factor in protein-free medium. The soluble CD4-H gamma 1 receptor, the production of which was not growth-associated, accumulated in the medium to concentrations of 40 micrograms/ml with a specific formation rate of 0.18 micrograms/10(6) cells/h in conventional cultures. The cell density was further increased by growing the cells in dialysis tubing or by using a perfusion system with cell retention. Because of the continuous exchange of nutrients and metabolic end-products average concentrations of 35 x 10(6) cells/ml were achieved. CD4-H gamma 1 accumulated in the dialysis tubing up to 1.3 mg/ml. After an initial rapid growth period, a ten-fold reduction in specific nutrient consumption rates and metabolic end-product formation was observed. Chimaeric proteins purified by protein G chromatography from conventional and perfusion cultures were indistinguishable when compared by SDS-PAGE, limited proteolysis and isoelectric focusing analysis (isoelectric point: 8.5-8.6). PMID- 1735776 TI - The use of spent renal dialysis membranes for the isolation of large numbers of human neutrophils for biochemical studies. Application to purification of the myeloid IgA receptor (Fc alpha R). AB - Human neutrophils (PMN) can be eluted from spent Cuprophan renal dialysis membranes in large numbers (10(9)-10(10) per dialyser cartridge) and in relatively high purity by washing the membranes with 0.35 M NaCl. This offers the possibility of isolating relatively large amounts (10(-4)-10(-3) g) of minor PMN proteins such as those expressed on the cell surface. Here the technique is applied to the purification of the neutrophil IgA receptor (Fc alpha R). Affinity chromatography on IgA-Sepharose of NP-40 extracts of 125I-labelled PMN isolated from fresh venous blood routinely gave a receptor preparation showing one diffuse band, Mr 50-70 kDa, upon analysis by SDS-PAGE and autoradiography. When the same method was used with larger numbers of unlabelled PMN from fresh venous blood or renal dialysis membranes a preparation was obtained which gave multiple bands upon analysis by SDS-PAGE silver stained gels due to contamination of the receptor with cytoplasmic proteins which bound non-specifically to the IgA Sepharose. Most of these contaminants could be removed by chromatography of the IgA-Sepharose eluates on wheat germ agglutinin-Sepharose. PMID- 1735777 TI - An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens. AB - Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens. Here we present improved haemolytic plaque-forming cell (PFC) assays detecting AbSC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides. These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays. In the case of anti-polysaccharide AbSC of the IgG isotype, the increase was as high as 7.4-11.8 times. Evidence is presented that the pronounced improvement in the detection of the latter is due to the presence of aggregating anti-IgG antibody from the beginning of the assay. It is proposed that in the case of low affinity of anti-polysaccharide antibodies aggregation of secreted monomeric antibody (IgG) is critical for plaque formation and increases the avidity of binding to target cells. PMID- 1735778 TI - IgG subclass distribution of anti-HBs antibodies following vaccination with cDNA HBsAg. AB - Serum samples were obtained during follow-up of nine young adults vaccinated over 1 year with cDNA hepatitis B antigen. The absolute amounts of anti-HBs IgG subclass antibodies present in the sera were determined by comparing the optical densities (OD) obtained using an antigen-specific ELISA with those obtained by serial dilutions of known amounts of human IgG1-4. The calibration curves for each IgG subclass were corrected for the corresponding coating efficiency. Our data suggest that HBs antibody responses of vaccinated subjects occur in all IgG subclasses but IgG1 and IgG2 are the major subclasses involved. PMID- 1735779 TI - Escherichia coli heat-stable enterotoxin (STa)-biotin conjugates for the titration of STa antisera by an enzyme-linked immunosorbent assay. AB - The development of a new approach to the diagnosis of infectious diarrhoea, caused by Escherichia coli heat-stable enterotoxin (ST), was preceded by a preliminary study. The purpose of the latter was to establish whether three preparations of ST produced by a human isolate of enterotoxigenic E. coli (STa), obtained at different steps of the purification procedure (involving Amberlite XAD2 resin chromatography (P3), a gel filtration chromatography on a Biogel P4 (P2) or a disc-gel electrophoresis (P1)), could be employed to titrate antisera to STa using an ST-biotin enzyme-linked immunosorbent assay (ELISA). The solid phase STa was obtained by first coupling the toxin to biotinyl-N hydroxysuccinimide and then binding this conjugate to avidin adsorbed to flat bottomed polystyrene microtitre plates. Using these reagents, the assay conditions were examined. Checkerboard tests determined optimal biotin-P3, P2 or P1 toxin conjugate concentrations to be used as the immunosorbent for P3, P2 and P1 antiserum titration. The immunosorbent prepared with STa purified only on Amberlite XAD2 resin was unable to differentiate significantly between P3, P2 or P1 antisera. Immunosorbent prepared with P2 or P1 detected widely differing titres between the three antisera and gave more sensitive results. Only small but questionable differences were observed between P2 and P1 toxin preparations. PMID- 1735780 TI - An oscillating bubble chamber for laboratory scale production of monoclonal antibodies as an alternative to ascitic tumours. AB - A simple roller bottle was constructed to house three dialysis tubes, each with a capacity of 75 ml. Cells were grown inside the dialysis tubing, which was immersed in ordinary DMEM medium without serum supplement. Cultures of hybridomas at medium or low density (2 X 10(5) cells/ml) could be expanded directly in the dialysis tubes to attain a high cell density of the order of 10(7)/ml. Continuous gentle stirring of the cells was possible, since the design causes a bubble to oscillate along the length of each tube. The six cell lines tested all gave antibody concentrations of between 1.1 and 2.3 mg/ml at 20 days. Such an in vitro apparatus obviates the need to employ ascites production, because it is as simple or simpler than the injection of mice, and the in vitro product is very rich in antibody, whilst containing low amounts of contaminating proteins. PMID- 1735781 TI - Separation of peripheral blood lymphocytes with low platelet and erythrocyte contamination, using ADP aggregation. AB - A simple and inexpensive method to obtain substantially platelet-free and erythrocyte-free lymphocyte preparations from human peripheral blood has been established, using a modification of the technique published by Vives et al. (1971). Lymphocyte levels of up to 3 x 10(6) per ml blood have been obtained, with 2-3% platelet and erythrocyte contamination per ml blood, by pre-aggregating platelets with low concentrations of adenosine 5'diphosphate (ADP). PMID- 1735782 TI - Measurement of lysozyme by an enzyme-linked immunosorbent assay. AB - In this study an enzyme-linked immunosorbent assay has been developed for the determination of lysozyme in saliva, serum and urine. The assay relies on the detection of specific protein rather than lytic activity, a property which has been shown to be most suitable for the quantitation of lysozyme in mucin containing substances. Our results indicate that no pretreatment is necessary for the immunochemical method. The assay is sensitive to concentrations as low as 1 microgram lysozyme/l. The intra-assay and inter-assay coefficients of variation were 5.9% and 15.8% respectively. The lysozyme level in whole saliva was 55.53 +/ 30.35 mg/l, in serum the level was 0.64 +/- 0.15 mg/l and in urine it was 0.17 +/- 0.22 mg/l. Comparisons between immunochemical determination and lytic assays showed a good correlation (serum, r = 0.79, P less than 0.01; saliva, r = 0.85, P less than 0.005; treated saliva, r = 0.96, P less than 0.001). PMID- 1735783 TI - Establishment of anti-human neuroblastoma-selective isotype-switch variants. AB - Isotype-switch variants of monoclonal antibodies occur spontaneously at low frequency in hybridoma cultures. We have established gamma 2b variants from the gamma 1/kappa antibody-secreting murine hybridoma CE7 and gamma 2a-secreting variants from a selected CE7 gamma 2b clone. The CE7 antibodies selectively recognize a cell surface glycoprotein of 185 kDa expressed on all human sympatho adrenomedullary cells. The switch-variants were obtained by a stepwise cloning strategy and selected by an isotype-specific solid-phase sandwich ELISA. The frequency of the switch variants was 1-2 x 10(-5) for both isotypes. Using ELISA inhibition technique it was demonstrated that the selected variants were able to bind to the same epitope of neuroblastoma as the original CE7 gamma 1. Southern blot analysis showed that the functionally rearranged VH and VL genes of CE7 gamma 1, CE7 gamma 2a and CE7 gamma 2b antibodies were identical. The N terminal FR1 amino acid sequence of the L chains was identical in all three isotypes and the H chains were blocked for Edman degradation. Regarding the possible applications of CE7 antibodies the different isotypes were assayed for their cytolytic activity as measured by complement-mediated 51Cr release of IMR-32 neuroblastoma cells. PMID- 1735784 TI - Simultaneous multiple synthesis of peptide-carrier conjugates. AB - Recently, the multipin approach for simultaneous multiple peptide synthesis was applied to the analysis of T cell determinants by using a novel cleavage method (Maeji et al., 1990). A diketopiperazine forming linker allowed cleavage of peptides into aqueous buffer which, without further purification, could be used immediately in cell culture assays. Another potential application of the technique is the simultaneous cleavage and coupling of peptides to immunogenic carriers. Without further purification the resulting conjugates can be used for the production of antipeptide antisera. The choice of carrier and conjugation chemistry is not restricted as peptide/pin cleavage occurs in aqueous solution over a range of pH and ionic strength. The method was assessed using the 2,4 dinitrophenyl group as a model hapten, diphtheria toxoid as the carrier, and N (epsilon-maleimidocaproyloxy)succinimide as the cross-linking reagent. The resulting DNP-DT conjugate was used to prepare high titered specific anti-DNP antisera in mice. PMID- 1735785 TI - Unexpected interaction of some anti-TNP hybridoma antibodies with Superose HPLC gel filtration resins. AB - Five different hybridoma antibodies (the isotypes IgG1, IgG2a and IgG2b), reactive with TNP, showed increased elution times when gel filtered on a Superose 12 HPLC column corresponding to apparent molecular weights ranging from 54 kDa to 120 kDa compared to the normal of 150 kDa. One of the antibodies (C1901-B4) was studied in detail showing that the unusual gel filtration behaviour was localized to the Fab part of the molecule. SDS-PAGE analysis showed that the intact antibodies had normal molecular weights. Gel filtration on a Toyosoda G-3000SW HPLC column and Sephadex G-150 as well as Sepharose 6B generally showed normal elution times. These results support the hypothesis that the retardation on the Superose gel is probably due to aromatic interactions between amino acid residues supposedly exposed in the hypervariable region (i.e., the antibody combining site) of the antibody, and the gel matrix which is rich in ether O-atoms created during the manufacturing process. If this hypothesis is correct one might expect such interactions between Superose resins and antibodies of many different specificities in which aromatic amino acids are exposed in the combining sites. PMID- 1735786 TI - Calculation of lytic units for the expression of cell-mediated cytotoxicity. AB - Over the past 10 years, the lytic unit has become the most common means by which activity is expressed in cell-mediated cytotoxicity assays. The strengths and weaknesses of the lytic unit as a summary of cytotoxicity are discussed, and computational methods reviewed. The fundamental "assumption of proportional effect" which is implicit in the interpretation of lytic units is described and empirically tested. Based on extensive data from the assay of human natural killer (NK) activity against K562 targets, simplified computational methods are recommended. The proposed methods are easily explained, may be made robust to occasional erratic data, and permit a reasonable interpretation of lytic units even when the assumption of proportional effect breaks down. PMID- 1735787 TI - Ciliary beating in three dimensions: steps of a quantitative description. AB - We document a novel approach for quantitative assessment of ciliary activity, exemplified in rapid three-dimensional cyclic motion of the frontal cirri of Stylonychia. Cells held under voltage-clamp control are stimulated by step pulses to elicit reproducible hyperpolarization- or depolarization-induced ciliary motor responses. High-speed video recording at 200 fields per second is used for imaging ciliary organelles of the same cell in two perspectives: the axial view and, following cell rotation by 90 degrees, the lateral view. From video sequences of typically 1 s, the contours of the cirral images are determined and digitized. Computer programs are established to (1) reduce an observed image to a "ciliary axis", (2) sort series of axes by template to generate an averaged ciliary cycle in 2D-projection, and (3) to associate the generalized axial and lateral 2D-images for generation of a sequence of three-dimensional images, which quantitatively represent the cycle in space and time. The method allows us to produce predetermined perspectives of images selected from the ciliary cycle, and to generate stereo views for graphical representation of ciliary motion. The approach includes a potential for extraction of the complete microtubular sliding program of a cilium under reproducible electric stimulation of the ciliary membrane. PMID- 1735788 TI - Diagnosis of atrial fibrillation from surface electrocardiograms based on computer-detected atrial activity. AB - A computerized method to detect atrial fibrillatory activity on the surface electrocardiogram is presented. After ventricular activity was canceled by creating a remainder electrocardiogram, significant differences were found in the percent power of the remainder electrocardiograms for a group of rhythms with atrial fibrillation (mean +/- SD; lead V1, 47.4 +/- 29.7%; lead II, 39.4 +/- 26.8%) and a control group (irregular rhythms or rhythms without readily detectable P waves; lead V1, 17.6 +/- 14.6%; lead II, 19.2 +/- 13.9%) for both leads (p less than 0.0001). A discrimination algorithm that classified a rhythm as atrial fibrillation if the percent power was greater than 32% and if noncoupled P waves were not present had a specificity of 90.0% and a sensitivity of 69.7% for the training set and a specificity of 87.8% and a sensitivity of 68.3% for the test set. In addition, the algorithm correctly detected all 66 of the 66 sinus rhythms tested. The algorithm produced good results that may be incorporated into arrhythmia interpretation systems to improve their specificity. PMID- 1735789 TI - Rate-dependent accessory pathway conduction due to phase 3 and phase 4 block. Antegrade and retrograde conduction properties. AB - Six patients who had antegrade phase 3 and phase 4 block in the accessory pathway were examined. In each patient, antegrade conduction over the accessory pathway was absent both at the sinus rate and at slower heart rates. During premature atrial stimulation a "window" of accessory pathway conduction was identified in all patients. The outer limits of the window ranged from 480 ms to 670 ms. The inner limits ranged from 410 ms to 620 ms. The durations of the window ranged from 20 ms to 160 ms. Three patients with orthodromic atrioventricular reentrant tachycardia showed preserved retrograde accessory pathway conduction. The remaining three patients had impaired retrograde accessory pathway conduction. One of the patients showed retrograde phase 4 block in the accessory pathway. In two patients, retrograde concealed conduction in the accessory pathway induced by ventricular stimulation prolonged the outer limit of the window in the antegrade accessory pathway conduction. These findings suggest that the mechanism of antegrade phase 3 and phase 4 block in the accessory pathway may be spontaneous diastolic depolarization in the accessory pathway and conduction disturbance at the ventricular and/or atrial insertion of the accessory pathway. PMID- 1735790 TI - Effect of pacing drive cycle length on induction of sustained monomorphic ventricular tachycardia. AB - To assess the effect of pacing drive cycle length on induction of sustained monomorphic ventricular tachycardia, 40 patients were prospectively studied in the drug-free state. Ventricular extrastimuli were sequentially delivered at the same coupling interval at each of three drive cycle lengths (600, 500, and 400 ms) before the coupling interval was shortened and the process repeated. This protocol was continued until sustained monomorphic ventricular tachycardia was induced at all three drive cycle lengths or until pacing was completed through three extrastimuli. Of the 27 patients in whom sustained monomorphic ventricular tachycardia was induced, tachycardia was induced at all 3 drive cycle lengths in 12 (44%), only 2 drive cycle lengths in 11 (41%), and only 1 drive cycle length in 4 (15%) patients. Although the yield of inducible ventricular tachycardia increased with each additional extrastimulus, this yield increased even further with the use of multiple drive cycle lengths. In 10 of 11 patients, failure to induce ventricular tachycardia at any drive cycle length was not due to failure to achieve at that drive cycle length the critical extrastimulus coupling interval required to induce tachycardia at other drive cycle lengths. Induction of sustained monomorphic ventricular tachycardia is often drive cycle length specific, and failure to induce tachycardia cannot be explained by failure to achieve critically short coupling intervals. Pacing at multiple drive cycle lengths increases the yield of induced ventricular tachycardia. PMID- 1735791 TI - Characteristic abnormal features of body surface potential maps predictive of ventricular tachycardia following coronary artery occlusion in dogs. AB - In a search for features predictive of ventricular arrhythmias in myocardial ischemia, the body surface potential maps of 17 dogs with coronary artery occlusion were studied. Ventricular tachycardia occurred in 9 (53%) of the 17 dogs. Multiple distribution of the abnormal potential minimum was found in 6 (67%) of the 9 dogs with (group A) and none of the 8 dogs without ventricular tachycardia (group B). The difference was statistically significant (p less than 0.01). The abnormal "early reversal" phenomenon of potential distribution was observed in 6 (67%) of group A and 7 (88%) of group B. The difference was not statistically significant (p greater than 0.05). The area of abnormal negative potential was 28.0 +/- 8.5 cm2 for group A and 14.5 +/- 5.5 cm2 for group B (p less than 0.001). The abnormal negative potential lasted for 25.4 +/- 3.5 ms in group A and 10.1 +/- 5.1 ms in group B (p less than 0.001). The abnormally early appearance of potential minimum lasted for 24.2 +/- 5.1 ms in group A and 10.5 +/ 5.4 ms in group B (p less than 0.001). The data suggest that the distribution, area, and duration of the abnormal negative potential of the body surface potential map are useful in the prediction of ventricular tachycardia associated with coronary artery occlusion. PMID- 1735792 TI - Effect of strontium on action potential repolarization in rabbit sinoatrial node cells. AB - Using standard microelectrode techniques, the effects of strontium (Sr++) ions on action potential (AP) repolarizations in rabbit sinoatrial node (SAN) cells were studied. In a nominally magnesium-free, calcium-free solution, Sr++ (0.5-3.55 mmol) produced an early afterdepolarization (EAD) and a prolongation of the AP. Until now, no experimental evidence has been presented in favor of an EAD mechanism in SAN cells. Superfusion of the SAN cells with 0.5 mmol Sr++ solution containing 1-5 mmol magnesium (Mg++) or 0.5 mmol calcium (Ca++) did not induce the EAD. Increasing the extracellular Mg++ to 1-5 mmol did not affect the EAD induced by superfusion with 3.55 mmol Sr++ solution. Increasing the extracellular Ca++ to 0.5 mmol suppressed the 3.55 mmol Sr(++)-induced EAD. The presence of 0.3 mmol manganese (Mn++) suppressed the EAD induced by superfusion with 0.5 mmol Sr++ solution. The EAD did not occur in the presence of 1 x 10(-6) mol nitrendipine or 2 x 10(-6) mol diltiazem hydrochloride. The presence of 0.03 mmol Mn++ did not significantly alter the 0.5 mmol Sr(++)-induced EAD. These results suggest that a slow inward Sr++ current through the Ca++ channel has an important role in the development of the EAD. PMID- 1735793 TI - Catheter ablation of hemodynamically compromising incessant atrioventricular tachycardia. AB - A 27-year-old woman was admitted to the Georgetown University Hospital with refractory hemodynamically compromising incessant atrioventricular tachycardia. A single left-sided accessory pathway was identified and successfully modified acutely. Endocardial delivery of direct current energy provided an extremely effective therapeutic intervention resulting in termination of atrioventricular tachycardia and restoration of stable hemodynamic status. Although a second ablation procedure was necessary to permanently interrupt accessory pathway conduction, the patient has remained free of symptoms without medications for 13 months. PMID- 1735794 TI - Atrioventricular nodal reentrant tachycardia with retrograde block induced by aprindine. AB - Two patients are described who had atrioventricular nodal reentrant tachycardia (AVNRT) with 1:1 relationship in the control state, but in whom a varying degree of VA block during AVNRT was observed during therapy with aprindine. Aprindine, however, did not cause anterograde blockade of conduction over the slow AV nodal pathway during tachycardia. These observations support the conclusion that the bulk of atrial muscle is not a requisite part of the tachycardia circuit in AVNRT and that antiarrhythmic drugs may have disparate effects on conduction in the retrograde and anterograde limbs of the circuit. PMID- 1735795 TI - Implications of macroscopic source strength on cardiac cellular activation models. PMID- 1735796 TI - Spontaneous beat-to-beat variability of the ventricular repolarization duration. AB - The spontaneous beat-to-beat variability of the ventricular repolarization duration was investigated in 21 healthy subjects (age 25-71 years; mean, 40 years) during the basal state in a recumbent position. For each subject, approximately 1,000 consecutive cycles were analyzed with an automated technique. The time series of the RR, QT, and RT intervals generate histograms that approximate normal distributions and have mean standard deviations of 57.0 ms, 5.4 ms, and 4.3 ms, respectively. Spectral analysis was used to detect rhythmical oscillations in these time series. The power spectra densities of both heart rate and ventricular repolarization during show peaks in the same frequency bands: low frequency (0.05-0.12 Hz) and high frequency (0.2-0.4 Hz). The power distribution between these two bands observed in the ventricular repolarization duration spectra was found to be the reverse of that in heart rate spectra (p less than 0.005). PMID- 1735797 TI - Nurses in the news: from invisible to visible. PMID- 1735798 TI - Issues and trends in nursing service administration education. AB - The Council on Graduate Education for Administration in Nursing (CGEAN) was established to further the development and improvement of graduate education for administration in nursing. The Council seeks to identify the nature and direction of education for administration in nursing in various healthcare systems, providing guidelines for programs offering administration. A major goal of CGEAN is facilitating dialogue between nursing service administrators and graduate level educators who are engaged in teaching and research related to administration in nursing. This column, sponsored by members of the Council, will analyze and respond to position statements and trends related to the delivery of health services and graduate education for administrators in nursing. PMID- 1735799 TI - Nurse executive practice--into the next millennium: from limbo dancer to pole vaulter. AB - Nurse executives, administrators, and managers are constantly being challenged by the changes in healthcare. Although it sometimes seems there is really nothing new, proactive visionary nurse administrators can rediscover, redesign, and redirect their own and others' activities to achieve organizational effectiveness. Such approaches require periodic examination of all strategies and practices--past, present, and future--for their relevance, practicality, and success. The editors of "Executive Development" reflect on topics important to organizational life. PMID- 1735800 TI - Decision-making autonomy in nursing. AB - Current nursing literature has suggested that nurses may have low needs or preferences for decision-making autonomy. In this study, the authors found that nurses differed in their preferences for decision-making autonomy in three types of work-related decisions. Employed nurses with a greater preference for autonomy were more satisfied with their jobs, and those with little or no such preference were less satisfied, as they gained decision-making influence over patient care and unit management. The authors discuss implications for designing and implementing decision-making programs. PMID- 1735801 TI - Stirring the social pot. Community effects of program and policy research. AB - The increasing interest in a national health program will lead to major changes in healthcare. The coming changes will be larger perhaps than those of the past decade and almost certainly will be outward--outside large institutions, into communities. Community relations will become increasingly important and therefore should become a part of studies to guide administrative decisions regarding program development. Administrators and their research collaborators should be aware of the unintended "side effects" of such community-oriented research. These effects have organizational and research implications that decision makers may choose to use to build community-organization alliances and promote public education to create supportive and informed consumers and a responsive healthcare system. PMID- 1735802 TI - Radiation protection for nurses. Regulations and guidelines. AB - Rules and regulations of federal agencies and state radiation protection programs provide the bases for hospital policy regarding radiation safety for nurses. Nursing administrators should work with the radiation safety officer at their institutions to ensure that radiation exposures to staff nurses will be as low as reasonably achievable and that special consideration will be given to pregnant nurses. Nurses' fears about their exposure to radiation can be greatly reduced through education. PMID- 1735803 TI - Critical pathways in home healthcare. AB - Administrators and directors of home health agencies are increasingly accountable for the productive use of resources and quality patient outcomes. However, few reliable ways exist to measure and influence these components. The author proposes the use of the critical pathway typically used in acute care case management as an efficient tool to guide home health nursing practice. The author presents the process for developing a critical pathway for congestive heart failure patients in a home health agency, as well as results of a study determining when nursing interventions were implemented. PMID- 1735804 TI - Head nurse role redesign. Improving satisfaction and performance. AB - In a correlational study with 110 head nurses in 10 hospitals, the author developed and tested a model for use in role redesign in nursing. Results provide data useful in the redesign of the head nurse role in hospitals in order to provide greater job satisfaction and improved outcomes for patients, nurses, and the organization. PMID- 1735805 TI - Into Iraq. Nursing organization in a combat support hospital. AB - Nurses from various backgrounds were joined together to become a cohesive combat support hospital during Operation Desert Shield and Operation Desert Storm. The author recounts how this was accomplished and how the hospital became a competent organization through a particular formula for success, along with preparation, discipline, and purpose. PMID- 1735806 TI - Satisfaction: it's more than effectiveness and efficiency. PMID- 1735807 TI - Case management in rural areas. Definition, clients, financing, staffing, and service delivery issues. AB - How does case management in rural areas differ from that in urban areas? How does the informal system of family, church, neighbors, and volunteers affect case management in rural areas? What are the strengths and problems of rural case management? The authors report the attitudes of rural case managers and attendees at a conference sponsored by two homecare organizations to these and other questions related to rural case management. PMID- 1735808 TI - Transformational leadership in nursing service. A test of theory. AB - What are the leadership dimensions that result in low turnover or work satisfaction? Intellectual stimulation, charisma, and individual consideration constitute aspects of transformational leadership that are suggested to enhance retention and staff satisfaction. In this study, the authors tested transformational leadership theory in one nursing department with an executive, 11 midlevel administrators, and 77 staff registered nurses. Findings support the predictions. Composed of teachable components, transformational factors are similar to leadership qualities described in magnet hospitals, offering positive implications for nursing administration and professional nursing practice. PMID- 1735809 TI - ProPAC. PMID- 1735810 TI - Anesthesia for premature and term infants: perioperative implications. PMID- 1735811 TI - Safety and efficacy of theophylline in children with asthma. PMID- 1735812 TI - Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines. AB - We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T. PMID- 1735813 TI - Management of bowel dysfunction in children with spinal cord disease or injury by means of the enema continence catheter. AB - Because bowel dysfunction in children with spinal cord impairment is a common and disabling problem that does not have adequate treatment, we evaluated the enema continence catheter developed in Toronto, Canada. Thirty-one children and their families were taught to administer a 20 ml/kg saline enema through this device. The children's bowel functions were evaluated 18 and 20 months after the start of the program. Six of the children dropped out of the study in the first 2 weeks and nine dropped out after between 18 and 30 months. For those remaining in the study, the proportion of continent stools rose from 28% to 94% (p less than 0.01); constipated stools dropped from 55% to 15% (p less than 0.01). Satisfaction with the bowel program increased, and five children were able to switch from diapers to lined underwear. No adverse effects were reported, and the amount of time required for toileting did not increase. Although compliance with the regimen was difficult for some families and its use carries potential risks, we believe that it can provide significant improvement in the bowel care of selected persons with spinal cord impairment. PMID- 1735814 TI - Limitations of the Glasgow Coma Scale in predicting outcome in children with traumatic brain injury. AB - OBJECTIVE: To study the hypothesis that, in the absence of an ischemic-hypoxic state, children with severe traumatic brain injury and with unfavorable Glasgow Coma Scale scores may have good recovery. DESIGN: Retrospective, observational, cross-sectional study with factorial design. SETTING: Inpatient population in a university hospital. PATIENTS: Seventy-nine children with traumatic brain injury admitted to the intensive care unit. INTERVENTIONS: All patients received close monitoring and strict control of intracranial pressure (less than 20 mm Hg) and cerebral perfusion pressure (greater than 60 mm Hg). MEASUREMENTS AND RESULTS: Admission Glasgow Coma Scale score, survival, need for cardiopulmonary resuscitation, presence of shock, peak intracranial pressure, duration of coma, Glasgow Outcome Scale score, and the results of neuropsychologic tests were analyzed. Of 79 children, 70 (89%) survived. Although the mortality rate was higher among patients with Glasgow Coma Scale scores of 3 to 5, 14 (64%) of 22 of these children survived. Nonsurvivors had a significantly higher incidence of shock and need for cardiopulmonary resuscitation. Except for two patients who had prolonged hypoxemia, all children, including those with Glasgow Coma Scale scores of 3 to 5, had a satisfactory outcome (Glasgow Outcome Scale scores of 4 or 5). Neuropsychologic outcome was not significantly different in the survivors with Glasgow Coma Scale scores of 3 to 5 and those with Glasgow Coma Scale scores of 6 or more. CONCLUSIONS: A low Glasgow Coma Scale score does not always accurately predict the outcome of severe traumatic brain injury; in the absence of hypoxic ischemic injury, children with traumatic brain injury and Glasgow Coma Scale scores of 3 to 5 can recover independent function. PMID- 1735815 TI - Prognostic indicators of joint destruction in systemic-onset juvenile rheumatoid arthritis. AB - We retrospectively reviewed the charts and radiographs of 38 patients with systemic-onset juvenile rheumatoid arthritis, attempting to identify early in the disease course the clinical and laboratory observations most predictive of the later development of destructive arthritis. In 12 of the patients, destructive arthritis developed within 2 years of disease onset. When first examined, these patients could not readily be differentiated from those in whom joint destruction did not develop, but they more commonly had hepatosplenomegaly (p less than 0.04), serositis (p less than 0.01), and a lower mean serum albumin concentration (26.7 vs 31.3 gm/L; p less than 0.02). However, by 6 months after onset, patients with destructive arthritis more frequently had persistent systemic symptoms (92% vs 12%; p less than 0.0001), polyarthritis (67% vs 19%; p less than 0.0005), a lower mean hemoglobin level (95 vs 114 gm/L; p less than 0.001), a higher mean leukocyte count (21.2 vs 10 x 10(9)/L; p less than 0.0003), a higher mean platelet count (794 vs 400 x 10(9)/L; p less than 0.0001), and a higher mean erythrocyte sedimentation rate (43 vs 24 mm/hr; p less than 0.05). Multivariate analysis of the results at 6 months revealed that persistent systemic symptoms and a platelet count greater than or equal to 600 x 10(9)/L were the variables most highly predictive of the later development of joint destruction. We conclude that patients at high risk for the development of destructive arthritis may be identified within 6 months of disease onset, thereby indicating the need for more aggressive early therapy. PMID- 1735816 TI - Association between severity of gastrointestinal prodrome and long-term prognosis in classic hemolytic-uremic syndrome. AB - To determine whether severity of the prodromal gastrointestinal illness is associated with the course and complications of the extraintestinal manifestations of hemolytic-uremic syndrome, we conducted a retrospective review of children (n = 509) hospitalized with hemolytic-uremic syndrome. Those who came to the hospital with colitis and rectal prolapse associated with hemolytic-uremic syndrome (group I, n = 40) were compared with an equal number of time-matched children with hemolytic-uremic syndrome but without prolapse (group II). Children in group I had evidence of more severe colitis than children in group II had, as indicated by increased frequency of bloody diarrhea (p less than 0.001) and longer duration of diarrhea (p less than 0.001). However, they also had more severe extraintestinal manifestations during hemolytic-uremic syndrome, including edema (p less than 0.0001), severe thrombocytopenia (p less than 0.0001), prolonged anuria (p less than 0.001), and seizures (p = 0.036). Long-term prognosis for recovery of renal function was worse for group I than group II. Within group II, patients with bloody diarrhea had milder extraintestinal illness than those with prolapse but more severe extraintestinal illness than those with watery diarrhea. Analysis of Kaplan-Meier survival curves demonstrated a better prognosis for return of normal renal function in the children with watery diarrhea but without prolapse (p = 0.009) than in children with bloody diarrhea or prolapse. These data demonstrate that the severity of the gastrointestinal prodrome reflects the severity of the extraintestinal acute microangiopathic process and the resulting long-term outcome. Widespread vascular damage, often followed by permanent sequelae, is characteristic of patients with the most severe colitis. PMID- 1735817 TI - Age-related changes in human blood lymphocyte subpopulations. AB - Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the cellular human immune system. Immunophenotypic markers were evaluated in 110 normal pediatric subjects, divided into groups of newborn infants, infants aged 2 days to 11 months, and children aged 1 to 6 years and 7 to 17 years; results were then compared with those obtained from 101 normal adults aged 18 to 70 years. Comparisons among age groups from newborn infants through adults reveal progressive declines in the absolute numbers of leukocytes, total lymphocytes, and T, B, and natural killer (NK) cells. The percentages of T cells within the total lymphocyte population increase with age, in both CD4+ and CD8+ subsets. Percentages of B and NK cells are higher in newborn infants than in adults. The expression of the activation markers interleukin-2R and HLA-DR on T cells increases with age, as does the NK-associated expression of CD57 on CD8 cells. The proportions of B lymphocytes that coexpress CD5 or CDw78 decrease with age, whereas expression of Leu-8 and CD23 increases. The proportion of CD4 cells bearing the CD45RA and Leu-8 markers is consistently lower in adults than in children. These data may serve as a reference range for studies of pediatric subjects. PMID- 1735818 TI - Urinary excretion of human growth hormone in children with short stature: correlation with pituitary secretion of human growth hormone. AB - Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children. PMID- 1735819 TI - Effect of growth hormone treatment on hyperinsulinemia associated with Turner syndrome. AB - To determine whether the insulin resistance in patients with Turner syndrome, which may be exaggerated by treatment with human growth hormone, leads to excessive insulin secretion, we applied the hyperglycemic glucose-clamp technique to produce a standard hyperglycemic stimulus (6.9 mmol/L, or 125 mg/dl, greater than fasting plasma glucose level for 120 minutes) in seven patients with Turner syndrome and in seven healthy children. These studies were repeated in the patients after 6 to 12 months of therapy with growth hormone. Fasting plasma levels of insulin were comparable in control subjects and patients before therapy but increased significantly in the patients after 6 to 12 months of treatment with growth hormone. Despite identical glucose increments in the two groups during the glucose-clamp procedure, both first- and second-phase insulin responses were significantly greater in the patients than in the control subjects. Moreover, the hyperinsulinemic responses to glucose were markedly exaggerated in the patients after their treatment with growth hormone, reaching values (first phase 474 +/- 100 pmol and second phase 826 +/- 100 pmol; p less than 0.02 vs pretreatment values) that were almost threefold greater than those in control subjects (p less than 0.001). Nevertheless, the rate of insulin stimulated glucose metabolism during the last 60 minutes of the clamp procedure was similar in all three groups of studies. Glycosylated hemoglobin, total cholesterol level, and blood pressure remained normal in patients after therapy with growth hormone. We conclude that glucose-stimulated insulin response is increased in patients with Turner syndrome and that these alterations are further exaggerated by treatment with growth hormone. These hyperinsulinemic responses appear to compensate for reductions in insulin sensitivity. PMID- 1735820 TI - Accelerated growth rates in children treated with growth hormone after renal transplantation. AB - To determine the usefulness of growth hormone treatment among children with renal allografts, we treated nine children with functioning renal transplants who were less than 16 years of age and had poor growth. The nine children, who were aged 12.6 +/- 4.0 years, had (1) heights greater than 2.5 SD less than the mean for age, (2) growth rates less than or equal to 5 cm/yr, and (3) additional growth potential, as assessed by bone age (8.9 +/- 2.8 year). Insulin-like growth factor I, thyrotropin, and thyroid hormone levels were normal for age in all children. Growth hormone treatment increased growth rates from 1.9 +/- 1.1 cm/yr to 7.2 +/- 1.8 cm/yr without accelerating skeletal maturation and without advancing pubertal status. During growth hormone treatment, serum creatinine concentration rose from 140 +/- 50 to 190 +/- 80 mumol/L (1.6 +/- 0.6 to 2.1 +/- 0.9 mg/dl) (p less than 0.05), and creatinine clearances decreased from 0.79 +/- 0.37 to 0.58 +/- 0.30 ml/sec per 1.73 m2 (47 +/- 22 to 35 +/- 18 ml/min per 1.73 m2) (p less than 0.05) but then remained stable. Growth rates of two patients returned to pretreatment rates when growth hormone treatment was discontinued after 5 and 7 months because of increased serum creatinine values. Growth hormone treatment may be useful as adjunctive therapy for increasing growth rates in selected children with renal allografts who have poor growth; however, serum creatinine concentrations should be closely monitored during such treatment. PMID- 1735821 TI - Descriptive study of genital variation in healthy, nonabused premenarchal girls. AB - This descriptive colposcopic study of the genitals of symptom-free young girls not thought to have been sexually abused was undertaken to contribute toward our understanding of normal female genital anatomy in this age group. Girls were examined and photographed, with labial traction in a supine frog-leg position while they were under anesthesia before minor elective surgery. The final study sample consisted of 79 premenarchal girls, aged between 3 months and 11 years 7 months (mean, 5 years 4 months). The study demonstrated wide anatomic variation and a high frequency of minor irregularities that have previously been noted in studies of sexually abused girls. Specific findings included increased vascularity (44%), midline avascular areas (27%), "ragged" posterior fourchette epithelium (18%), notch configuration of the posterior fourchette (10%), delicate tethers between the hymen and perihymen (14%), hymenal bumps between the 3 and 9 o'clock positions (11%), and asymmetry of the hymenal tissue (9%). Girls who at initial examination had apparently abnormal vestibules had either large hymenal orifices (11%) or multiple irregularities (11%). The study emphasizes the danger of overinterpreting small anatomic findings when one is evaluating the possibility of sexual abuse in girls; such findings may lie within the range of normal variation. PMID- 1735822 TI - Sexual abuse in girls: what have we learned about genital anatomy? PMID- 1735823 TI - Association of poor clinical status and heavy exposure to tobacco smoke in patients with cystic fibrosis who are homozygous for the F508 deletion. AB - We examined the association between clinical status and exposure to tobacco smoke in 44 patients homozygous for the F508 cystic fibrosis mutation. Heavy exposure to tobacco smoke was significantly associated with lower Shwachman scores, poorer results of pulmonary function tests, and a fivefold increase in the number of pulmonary-related hospitalizations during the previous year. PMID- 1735824 TI - The clitoral index: a determination of clitoral size in normal girls and in girls with abnormal sexual development. AB - Clitoral measurements were obtained in normal children; small increases in clitoral dimensions were associated with growth and puberty. Patients with androgen excess had major increases in clitoral size, clearly different from normal values. PMID- 1735825 TI - Quadriplegia after chiropractic manipulation in an infant with congenital torticollis caused by a spinal cord astrocytoma. AB - An infant with congenital torticollis underwent chiropractic manipulation, and within a few hours had respiratory insufficiency, seizures, and quadriplegia. A holocord astrocytoma, with extensive acute necrosis believed to be a result of the neck manipulation, was found and resected. We believe that every child with torticollis, regardless of age, should undergo neurologic and radiologic evaluation before any form of physical treatment is instituted. PMID- 1735826 TI - Acute infantile cardiomyopathy as a presenting feature of mucopolysaccharidosis VI. AB - An infant with a diagnosis of acute infantile cardiomyopathy was subsequently shown to have mucopolysaccharidosis VI. The mucopolysaccharidoses should be included in the differential diagnosis of infantile cardiomyopathy. PMID- 1735827 TI - Reversible hypertrophic cardiomyopathy associated with nesidioblastosis. AB - An infant with persistent hyperinsulinism had hypertrophic cardiomyopathy that progressed until near-total pancreatectomy was performed. After pancreatectomy the condition resolved. Hyperinsulinism may be a cause of treatable cardiomyopathy. PMID- 1735828 TI - Paraneoplastic syndrome manifesting as chronic cerebellar ataxia in a child with Hodgkin disease. AB - An 8-year-old boy had nausea and vomiting associated with nystagmus, ataxia, and dysarthria of acute onset. Three years later he had a mass in the anterior mediastinum as a result of Hodgkin disease of mixed cellularity. This association of paraneoplastic cerebellar degeneration with Hodgkin disease has been described in adults. PMID- 1735829 TI - Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. AB - Long-term studies of a child with Gaucher disease indicated that the response to treatment with macrophage-targeted glucocerebrosidase (glucosylceramidase) is dose dependent, and that the hematologic response precedes the skeletal response. PMID- 1735830 TI - Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis. AB - We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis. PMID- 1735831 TI - Hypertrophic cardiomyopathy associated with dexamethasone therapy for bronchopulmonary dysplasia. AB - The potential induction of cardiac effects by high-dose dexamethasone therapy was evaluated prospectively in 13 respirator-dependent infants with bronchopulmonary dysplasia by means of two-dimensional and M-mode echocardiography. The initial divided dose of dexamethasone was 500 micrograms/kg per day, tapered progressively for as long as 6 weeks. Evaluations were made before treatment and at 3, 7, 14, 21, 28, 35, and 42 days after the start of dexamethasone therapy. This regimen was associated with a significant (p less than 0.01) increase in thickness of the interventricular septum (2.60 +/- 0.09 to 4.00 +/- 0.16 mm), diastolic left ventricular free wall (2.80 +/- 0.13 to 4.06 +/- 0.20 mm), and diastolic right ventricular free wall (1.55 +/- 0.08 to 2.02 +/- 0.12 mm). In addition, seven dexamethasone-treated infants but no control infants had systolic anterior motion of the mitral valve (p less than 0.001). These effects were transient, reached their maximal degree by the third week of treatment, and approached pretreatment conditions by the sixth week of treatment. Ejection fraction was not affected; heart rate and mean arterial pressure were transiently increased during dexamethasone therapy. We conclude that a transient absolute myocardial hypertrophy is associated with dexamethasone therapy in infants with bronchopulmonary dysplasia. The mechanism or mechanisms through which this hypertrophy arises and the cardiopulmonary implications are unclear. PMID- 1735832 TI - Relationship between determinants of oxygen delivery and respiratory abnormalities in preterm infants with anemia. AB - To study the relationship between anemia and breathing abnormalities in preterm infants, we measured oxygen supply and demand in two groups of anemic infants less than or equal to 32 weeks of gestational age. Six-second apnea density was less than 1% in one group and greater than or equal to 5% in the other. There were no differences in hemoglobin concentration, available oxygen, oxygen consumption, or Doppler-determined cardiac output between the two groups of infants. Furthermore, in anemic preterm infants with apnea density greater than or equal to 5%, reductions in 6-second apnea density were similar after erythrocyte transfusion (mean +/- SEM: from 8.6% +/- 1.1% to 4.7% +/- 0.7%) or after an isovolemic infusion of 5% albumin (from 9.0% +/- 1.4% to 4.7% +/- 0.7%). These results show no relationship between measures of oxygen delivery and respiratory irregularities, and indicate that volume expansion may play a role in ameliorating the pneumocardiogram abnormalities. PMID- 1735833 TI - Neonatal hematocrit and maternal glycemic control in insulin-dependent diabetes. AB - We hypothesized that in infants of diabetic women neonatal hematocrit would correlate with third-trimester maternal glycemic control. Neonatal hematocrit correlated with the maternal total glycosylated hemoglobin level at delivery (r = 0.36; p less than 0.05) but not at 36 weeks of gestation in 32 mother-infant pairs. Improved maternal glycemic control during late gestation may decrease the incidence of neonatal polycythemia. PMID- 1735834 TI - Phototherapy and the brain-stem auditory evoked response in neonatal hyperbilirubinemia. AB - The latencies of peak V and interpeaks I-V and III-V in the brain-stem auditory evoked response of infants with hyperbilirubinemia before phototherapy were significantly greater than those in a control group of infants. These values of the brain stem auditory-evoked response improved significantly during phototherapy and correlated significantly with the declining bilirubin levels. Improvement continued after phototherapy, despite a rebound of serum bilirubin concentrations. PMID- 1735835 TI - Factors associated with condom use among sexually active female adolescents. AB - A health belief model of condom use was used to identify factors associated with condom use in 390 sexually active female adolescents, aged 12 through 19 years, recruited at the time of a visit for reproductive health care. Fifty-six percent were white and the remainder black. Nineteen percent had genitourinary infections with Chlamydia trachomatis. Forty-six percent reported having had more than one sexual partner in the preceding year. Reported condom use for at least one specific reason (prevention of pregnancy, sexually transmitted disease, or acquired immunodeficiency syndrome) increased as behavioral, emotional, and sexually transmitted disease risk decreased, and as cognitive maturity and positive condom attitudes increased. Although uses of condoms to prevent pregnancy, sexually transmitted disease, and acquired immunodeficiency syndrome were positively intercorrelated, each made a contribution to explaining condom use at most recent coitus (odds ratios 2.95, 3.96, and 2.81, respectively). After statistical adjustment for the reported reasons for previous condom use, behavioral risk was the only additional factor associated with condom use at the most recent sexual encounter; women who participated in more risk behaviors (substance and alcohol use and minor delinquency) were less likely to have used a condom (odds ratio 0.61). Knowledge about sexually transmitted disease and acquired immunodeficiency syndrome, and concurrent use of contraceptive pills, were not related to condom practices. The data suggest that adolescents' perceptions about condoms, including the individual functions of condoms for contraception and for prevention of sexually transmitted disease, may be important in determining their use. Engaging in unprotected intercourse may be part of a larger behavioral domain that includes other unhealthy behaviors. PMID- 1735836 TI - Association of pulmonary hypertension with congenital portal hypertension in a child. PMID- 1735837 TI - Hypercalciuria in osteogenesis imperfecta. PMID- 1735838 TI - Addendum to report of partial hypoxanthine-guanine phosphoribosyl transferase deficiency. PMID- 1735839 TI - "Transient" congenital hypoparathyroidism. PMID- 1735840 TI - Oral captopril test in children. PMID- 1735841 TI - Kawasaki disease and rug shampooing. PMID- 1735842 TI - Graduate medical education. PMID- 1735843 TI - Neutrophil values in infants born at high altitudes. PMID- 1735844 TI - Hyperinsulinemia, cardiomyopathy, and diazoxide therapy. PMID- 1735845 TI - Results of laboratory surveillance of very low birth weight infants treated with a synthetic surfactant. AB - During two randomized, controlled trials comparing single prophylactic doses of air placebo and a synthetic surfactant, Exosurf Neonatal, many routine laboratory measurements were made in small premature infants during the first week of life. Values for serum electrolytes, urea, creatinine, phospholipid, cholesterol, glucose, calcium, bilirubin, and liver enzymes, as well as for hemoglobin, leukocyte and platelet counts, and urinalysis, did not differ between the placebo and surfactant-treated infants. There was no evidence that prophylactic administration of this synthetic surfactant causes alterations in standard laboratory tests in small premature infants. PMID- 1735846 TI - Pulmonary mechanics and energetics in preterm infants who had respiratory distress syndrome treated with synthetic surfactant. AB - Pulmonary mechanics and energetics were determined in 32 neonates with respiratory distress syndrome, who were randomly assigned to receive treatment with an exogenous synthetic surfactant, Exosurf Neonatal, or air placebo. Pulmonary mechanics were measured before and 2 hours after surfactant (n = 13) or air placebo (n = 19) treatment, then longitudinally at 24, 48, and 72 hours after treatment, and again at 7, 14, and 28 days of age. There were no significant differences in the values for pulmonary mechanics or energetics 2 hours after the first dose of surfactant. Improvement in pulmonary mechanics was apparent 24 hours after surfactant treatment, when dynamic compliance was 36% greater than in the placebo group (p less than 0.03). Lung compliance values were also higher in surfactant-treated infants 48 and 72 hours after treatment, with a maximal increase of 64% at 7 days of age (p less than 0.03). Surfactant treatment also caused a significant decrease in total pulmonary resistance at 48 and 72 hours after initial treatment and at 14 days of age (p less than 0.04). Similarly, a decrease in flow-resistive work of breathing was demonstrated 24, 48, and 72 hours after surfactant treatment. At 28 days of age, pulmonary mechanics were not different in the two groups. We conclude that beneficial effects of surfactant on pulmonary mechanics were not apparent 2 hours after dosing but were evident 24 hours after dosing and persisted for the first 7 to 14 days of life. PMID- 1735847 TI - Pulmonary mechanics in premature infants one month after treatment with synthetic surfactant. AB - During the double-blind, multicenter trials of the synthetic surfactant Exosurf Neonatal, we measured pulmonary mechanics at 28 days of age in 30 surfactant- or placebo-treated infants. In the 20 surfactant-treated and 10 air-treated infants studied, there were no differences in lung compliance or resistance at 28 days of age. These observations suggest that improvements in pulmonary function reported early in the neonatal course after the administration of exogenous surfactant are not detectable at 28 days of age. PMID- 1735848 TI - Energy expenditure during synthetic surfactant replacement therapy for neonatal respiratory distress syndrome. AB - Little information is available on the energy expenditure of infants with increased work of breathing from respiratory distress syndrome (RDS). A study was carried out to determine whether surfactant replacement therapy modifies respiratory gas exchange in newborn infants with RDS and an arterial-alveolar oxygen tension ratio of less than 0.22. In a double-blind, placebo-controlled, rescue trial, infants received either two 5 ml/kg doses of a synthetic surfactant, Exosurf Neonatal, or air placebo. Of 23 infants ventilated for RDS, 11 were randomly assigned to receive air and 12 to receive surfactant. Oxygen consumption, carbon dioxide production, respiratory quotient, and metabolic rate were measured by computerized, closed-circuit, indirect calorimetry. Concomitantly, transcutaneous oxygen and carbon dioxide tension were continuously recorded. Oxygen consumption and carbon dioxide production remained constant during the period infants received surfactant. In patients randomly assigned to surfactant, a decrease in respiratory quotient was observed after the first (p less than 0.025) but not the second dose. This decrease was possibly related to a change in substrate utilization. The improved clinical outcomes reported among infants receiving surfactant were not accompanied by changes in energy expenditure. PMID- 1735849 TI - Controlled trial of a single dose of synthetic surfactant at birth in premature infants weighing 500 to 699 grams. The American Exosurf Neonatal Study Group I. AB - In a multicenter, double-blind, placebo-controlled trial conducted at 23 hospitals in the United States, a single prophylactic 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm. Despite stratification at entry by birth weight and gender, by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group. Among infants receiving synthetic surfactant, improvements in oxygen requirements were significant at 2 hours after birth (p = 0.014) and persisted for 3 days (p = 0.001); improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth (p = 0.01) and persisted for 3 days (p = 0.008). Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth (p = 0.622 and 0.083, respectively), but became significant thereafter and persisted for 3 days (p = 0.002). Pneumothorax was reduced by slightly more than half (25 vs 11; p = 0.014); death from respiratory distress syndrome (RDS) was also reduced (26 vs 15; p = 0.046). Overall neonatal mortality, however, was not significantly reduced (58 vs 46; p = 0.102). Other complications of RDS and prematurity were not altered, except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant (2 vs 12; p = 0.006). These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function, incidence of air leak, and death from RDS but not overall mortality. The only safety problem identified was an increase in pulmonary hemorrhage. PMID- 1735850 TI - Elastase activity and surfactant protein concentration in tracheal aspirates from neonates receiving synthetic surfactant. AB - Neutrophil elastase activity and the concentration of surfactant proteins A and B (SP-A, B) were measured in tracheal aspirate fluid from preterm neonates who were treated with the synthetic surfactant Exosurf Neonatal or air placebo in randomized, placebo-controlled, clinical trials. Elastase activity was transiently reduced in surfactant-treated infants on the second day of life, but the reduction was not sustained. In placebo-treated infants with established respiratory distress syndrome, tracheal aspirate SP-A was low on the first day of life and increased with time as respiratory distress syndrome resolved. In infants with respiratory distress syndrome treated with surfactant, significantly higher levels of SP-A were observed by 2 days after treatment and were maintained through at least the sixth day of life. These data suggest that lung inflammation is not increased and that endogenous surfactant secretion may be stimulated, not suppressed, by treatment with synthetic surfactant. PMID- 1735851 TI - Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: an autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group. AB - In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal. PMID- 1735852 TI - Retrospective search for bleeding diathesis among premature newborn infants with pulmonary hemorrhage after synthetic surfactant treatment. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group. AB - In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal, involving infants with birth weights 700 gm or greater the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To determine whether this apparent increase in pulmonary hemorrhage was the result of a bleeding diathesis, we retrospectively reviewed charts for 39 of 41 infants with clinical pulmonary hemorrhage. The incidence of nonpulmonary bleeding was the same in control- and surfactant-treated infants. Platelet counts, hematocrit values, and the number of transfusions with platelets or red blood cells did not differ between the two groups. There was no evidence that surfactant treatment was specifically associated with a generalized bleeding diathesis. PMID- 1735853 TI - Postoperative pressure elevation. A rational approach to its prevention and management. PMID- 1735854 TI - Active transport system of prostaglandins: clinical implications and considerations. AB - We hypothesize that two factors are essential in the development of epinephrine induced cystoid macular edema (CME): (1) the stimulation of prostaglandin synthesis by some tissues, presumably the anterior uvea by epinephrine; (2) the dysfunction of the active transport (Bito's pump) which is responsible for the removal of prostaglandins from intraocular fluids. We conducted several experimental studies to confirm these hypotheses. The results strongly suggest that epinephrine maculopathy is induced by a mechanism involving prostaglandins or, possibly, other related eicosanoids and not simply by epinephrine itself, as has been postulated. This suggests the existence of some common factors in the pathogenesis of epinephrine maculopathy and aphakic or pseudophakic CME. PMID- 1735855 TI - Postoperative inflammation following cataract extraction caused by bacterial contamination of the cleaning bath detergent. AB - Five of 16 patients who had uncomplicated cataract extraction with intraocular lens (IOL) implantation within a 2.5 day period experienced increased anterior segment inflammation on their first postoperative day. Four of these five patients had phacoemulsification and one a planned extracapsular cataract extraction. All had posterior chamber IOL implantation in the capsular bag. In all patients, this anterior segment inflammation cleared with topical steroids over two to three weeks with no evident residual ocular effects. A careful search for the possible cause of the inflammation showed that the ultrasonic cleaning bath and Weck liquid detergent used to clean the instruments contained Klebsiella pneumoniae bacteria. Further investigation demonstrated the presence of a heat stable endotoxin produced by the bacteria. We postulate that endotoxin remaining on the instruments after cleaning and sterilization caused this postoperative anterior segment inflammation. To the best of our knowledge, these are the first reported cases caused by contaminated liquid detergent. PMID- 1735856 TI - Excimer laser ablation of a corneal protuberance. AB - The ablation of a post-traumatic superficial corneal nodule with an argon fluoride excimer laser is reported. Three months postoperatively the area had a smooth surface with no distortion of adjacent cornea. PMID- 1735857 TI - Consultation section. A female with unilateral high myopia has become contact lens intolerant and developed an exodeviation of the myopic eye when wearing spectacles. PMID- 1735858 TI - Collagel--a new viscoelastic substance for ophthalmic surgery. AB - A clinical trial comparing the viscoelastic properties of Collagel (human collagen) and Healon (sodium hyaluronate) was performed. Collagel was well tolerated and produced no untoward reaction in the eye. Flare cell measurement was performed during the seven day postoperative period. The initial peak and decline of flare and cell determination showed a similar course in groups treated with Collagel or Healon. A transient increase in intraocular pressure was seen. Endothelial cell loss following surgery was similar in the Collagel and Healon groups. There were no significant differences in intraocular pressure, corneal thickness, endothelial cell density, or visual acuity during the postoperative period. These results suggest that this new viscoelastic substance is comparable to Healon in respect to the parameters described. PMID- 1735859 TI - Three versus four radial keratotomy incisions. AB - Radial keratotomy (RK) is currently performed with four or eight semi-radial incisions. To evaluate the effect of a theoretically more stable three-incision RK pattern, centripetal incisions were made in 16 human donor eyes (eight pairs), using a double-edged diamond blade set to 90% of central pachymetry and a 3.5 mm optical clear zone. Intraocular pressure was maintained at 15 mm Hg during surgery and while keratometry readings were made. One randomly selected eye of each pair had three radial incisions made at 12, 4 and 8 o'clock; the other eye had four radial incisions at 12, 3, 6, and 9 o'clock. Corneal flattening was 6.08 diopters (D) with four incisions and 4.84 D with three incisions (P less than .05). Astigmatism increased 0.44 D and 0.69 D, respectively (P greater than .1). Histologically measured mean incision depth (77.4%) did not differ significantly between the groups (P greater than .1). This study shows that 80% of the effect of a four-incision RK pattern can be obtained with a theoretically more stable three-incision pattern. PMID- 1735860 TI - Excimer laser intrastromal keratomileusis: case reports. AB - We report the results in six eyes on which we performed a new surgical method: intrastromal corneal excimer laser photoablation following lamellar corneal keratectomy with a microkeratome. The study was designed to evaluate the clinical and refractive efficacy of the procedure, to assess the behavior of the cornea following stromal photoablation, and to evaluate the relationship between the number of laser pulses and the decrease of myopia. The technique demonstrated an excellent corneal response to photoablation but a poor refractive predictability. PMID- 1735861 TI - Effect of small incision intraocular lens surgery on postoperative inflammation and astigmatism. A study of the AMO SI-18NB small incision lens. AB - A single center, single surgeon, randomized, prospective clinical trial was performed comparing the effectiveness of small (3.5 mm to 4.0 mm) incision intraocular lens surgery and a larger (6.0 mm) incision in improving uncorrected visual acuity and reducing post-operative inflammation and surgically induced astigmatism. One hundred twelve eligible unilateral cases were randomized to receive a 3.5 mm to 4.0 mm incision with implantation of an Allergan Medical Optics three-piece SI-18NB silicone lens (56 cases) or a 6.0 mm incision with implantation of a three-piece biconvex poly(methyl methacrylate) lens (56 cases). At one day after surgery, significantly (P less than .01) more patients with 3.5 mm incisions had 20/40 or better uncorrected visual acuity than patients with 6.0 mm incisions (45% vs 20%). Forty percent of patients with 6.0 mm incisions vs 14% of patients with 3.5 mm incisions had visual acuities of 20/100 or worse. At one day after surgery, the larger incision group had significantly higher (P less than .01) mean keratometric cylinder (2.28 diopters vs 1.28 diopters in the small incision group). The two groups were comparable by three months. Laser flare/cell meter measurements were taken for each group but showed no significant differences in mean flare or cell measurements between the groups. PMID- 1735862 TI - Ultrastructure of cells cultured onto various intraocular lens materials. AB - The response of three cell types (human fibroblasts, monocytes, and platelets), cultured or seeded onto different intraocular lens materials, was analyzed by ultrastructural examination. The materials considered were poly(methyl methacrylate) (PMMA), heparin surface-modified PMMA, plasma-treated PMMA, and hydrogel. Significant differences in density and distribution of the cultured cells were demonstrated among these materials. The ultrastructure of the cells appeared to be normal, except in one case. Disorganization of the points of focal contact and of the cytoskeletal elements was found in the fibroblasts cultured onto all materials except PMMA. Morphological evidence of cell activation was observed for some materials, but this requires confirmation by more specific immunocytochemical tests. PMID- 1735863 TI - Inflammatory response in the rabbit eye after intraocular implantation with poly(methyl methacrylate) and heparin surface modified intraocular lenses. AB - Early inflammatory responses in rabbit eyes after anterior chamber implantation with poly(methyl methacrylate) (PMMA) and heparin surface modified intraocular lenses (IOLs) and after cataract extraction and implantation with PMMA and heparin surface modified intraocular lenses (IOLs) were investigated between 1 and 30 days postoperatively. The number of white blood cells in the aqueous humor, the distribution of white blood cell subsets, and the interleukin-1 (IL 1b) levels were studied. At one day postoperatively, there was a significantly smaller number of white blood cells in eyes with heparin surface modified IOLs than in eyes with PMMA IOLs after both anterior chamber implantation and cataract surgery and capsular bag implantation. At one day postoperatively, 87% of the cell population in eyes with PMMA IOLs were neutrophilic granulocytes. Two days later the neutrophilic granulocytes had decreased to 13% and at seven days they were gone. At 14 days the frequency was 7% and at 30 days it was 27%. The fraction of monocytes/macrophages in the cell population was 9% (day 1), 79% (day 3), 94% (day 7), 81% (day 14), and 72% (day 30). The fraction of lymphocytes was low throughout the test period (1% to 10%). The percentages were almost the same in eyes with heparin surface modified IOLs and there was no significant difference in the distribution of white blood cell subsets between the two lens materials. The IL-1 was not detected in any of the samples (day 3, day 7, and day 30). Inactivated macrophages and/or levels under detection limits could be the reason.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735864 TI - Use of in vitro models of bovine corneal endothelial cells to determine the relative toxicity of viscoelastic agents. AB - Healon, Viscoat and Amvisc Plus (Amvisc+) are commercial preparations containing hyaluronic acids of different molecular weights and viscosities. Cytotoxicity of these preparations to the corneal endothelium may be a factor in postsurgical recovery of the cornea. Using different in vitro models of bovine corneal endothelial cells (BCEC), three experiments to compare the possible detrimental effects of these viscoelastic agents were designed. In the confluent model, confluent BCEC were exposed to viscoelastic agents and the control to Balanced Salt Solution Plus (BSS+) for one hour and the nuclear density (nuclei/mm2) was assessed at 24 and 168 hours. At both times, the BCEC exposed to Healon showed the highest nuclear densities. In the preconfluent model, BCEC were treated for one hour at 48 hours post-seeding. The nuclear density of the BCEC was assessed at 24 hours. The BCEC exposed to Healon showed the highest density, followed by those exposed to Amvisc+ and then Viscoat. In the proliferation model, BCEC were cultured in media containing 1%, 5%, and 10% viscoelastic agents. The growth curves based on nuclear densities at 0, 24, 72, 120, and 168 hours in all treatment groups did not differ significantly from the control. The results indicate that the undiluted Healon was significantly less toxic in the preconfluent and confluent BCEC models. PMID- 1735865 TI - Heparin surface modified intraocular lenses. Three-month follow-up of a randomized, double-masked clinical trial. AB - Two types of intraocular lenses (IOLs) were used in a controlled, randomized, double-masked clinical trial. The study lens was a one-piece, poly(methyl methacrylate) (PMMA) lens with heparin grafted on the entire surface. The control lens was identical in all respects but lacked the heparin surface. The IOLs were implanted in the capsular bag after extracapsular cataract extraction in 266 patients. No unexpected reactions or severe complications occurred. The postoperative visual acuity of all cases at the three-month visit was 20/40 or better in 91.6% of the heparin group and in 86.2% of the control group. When excluding cases with preoperative pathology, 97% of the heparin group and 95% of the control group had a visual acuity of 20/40 or better. A mild iritis was observed in one case of the heparin group and in four cases of the control group at three months. At three months there was a statistically significant difference between the heparin surface modified and control IOLs for both the number of patients with cellular precipitates and the number of precipitates per IOL. From the present data we conclude that during the first three postoperative months heparin surface modified lenses are more biocompatible than PMMA lenses. PMID- 1735866 TI - Indications for and results of intraocular lens explantation. AB - We reviewed the medical records of 97 patients who had 101 consecutive intraocular lens (IOL) explantation procedures, with or without exchange, at the University of Florida Eye Center from January 1, 1983, to December 31, 1987. The majority of the removed IOLs were anterior chamber styles (53.9%), followed by iris-fixated lenses (33.7%). The most common indications for surgery included pseudophakic bullous keratopathy (PBK)--69%, uveitis-glaucoma-hyphema (UGH) syndrome--9%, and IOL instability--7%. The best visual outcome was seen in patients with IOL instability; 50% achieved 20/40 or better visual acuity. Forty one percent of patients with PBK, who had IOL explantation/exchange combined with penetrating keratoplasty, achieved 20/40 or better visual acuity. The poorest visual outcome was seen in patients with the UGH syndrome; 83% had a final acuity of 20/200 or worse. However, these patients achieved resolution of their pain and inflammation and better control of their intraocular pressure as a result of the surgery. Complications leading to IOL explantation tended to occur months to years after the original surgery in patients with closed-loop, semi-flexible anterior chamber lenses and iris-fixated lenses. Posterior chamber lenses were most often removed because of complications unrelated to the implant. PMID- 1735867 TI - Optical quality of intraocular lenses. AB - The ANSI Z80.7 standard for intraocular lens quality is being updated. This paper identifies areas that require revision and suggests that a clear distinction between the lens design and the quality control test methods be made. The standard monofocal lens design consists of two spherical surfaces, and lens power can be specified by the thick lens equation, using body temperature refractive index values at a wavelength of 550 nm. Interferometry might be used as a primary manufacturing test method for poly(methyl methacrylate) lenses; tolerance values for lens surface errors are suggested. Other test methods can also be used. Measuring the modulation transfer function in fluid may be the most useful. PMID- 1735868 TI - Minimizing anisometropia in bilateral pseudophakia. AB - One hundred twenty patients who had bilateral posterior chamber intraocular lens implantation were analyzed for postoperative anisometropia. All pairs of lenses had the same A constant and similar designs. Several parameters were analyzed to identify patients at higher risk for clinically significant anisometropia upon implantation of the second eye and determine whether the results of the first eye could be used to modify the implant power selected for the second eye to reduce the risk of anisometropia. In most cases, simply using the value of the linear regression prediction for emmetropia in the second eye without modifications minimized anisometropia. PMID- 1735869 TI - Effect of music therapy in the postanesthesia care unit: a nursing intervention. AB - This study examined the effect of music on pain, hemodynamic variables, and respiration in the PACU, and the impact of music on patients' recall of their PACU experience. Sixty patients scheduled for thyroid, parathyroid, or breast surgery under general anesthesia were studied. Patients were randomly assigned into three groups: group 1, control, not wearing headphones; group 2, wearing headphones but hearing no music; and group 3, wearing headphones and listening to music. A visual analogue pain scale was used to rate patients' perception of pain. There was no difference in pain level, morphine requirement, hemodynamics, respiration, or length of stay in the PACU among the 3 groups, yet the music group was able to wait significantly longer before requiring analgesia on the nursing unit. Patients who listened to music perceived their PACU experience as significantly more pleasant than the patients in the other two groups as recalled both 1 day and 1 month later. PMID- 1735870 TI - Acute postoperative hypertension in the hypertensive patient. AB - Acute postoperative hypertension (APH) has been documented in the PACU. Over half of the patients who exhibit APH have pre-existing primary hypertension. Sustained blood pressure (BP) elevation increases the risk of myocardial ischemia, infarction, surgical site bleeding, or cerebral hemorrhage in these patients. Following surgery and anesthesia, increased sympathetic stimulation caused by a high level of circulating catecholamines can lead to APH. Some direct perioperative stimulants include pain, anxiety, hypoxia, hypercapnia, hypothermia, shivering, volume overload, and bladder distension. Nursing interventions are directed toward identifying and relieving the cause of APH. Antihypertensive drug therapy with vasodilators or adrenergic inhibitors is used if initial nursing interventions are not effective. Vasodilators frequently used are hydralazine, sodium nitroprusside, and nitroglycerin. Nicardipine has recently been introduced as an intravenous calcium channel blocker. Vasodilators are effective in BP reduction but may cause reflex tachycardia when used alone. Adrenergic inhibitors, such as esmolol and labetalol, block alpha and/or beta receptors to decrease heart rate and BP. Labetalol's effectiveness, relative freedom from side effects, and ease of administration have made it a useful drug in the treatment of APH. PMID- 1735871 TI - Practical points in understanding local anesthetics. AB - It has been the purpose of this article to discuss the pharmacology and physiology of local anesthetics. By having an understanding of local anesthetics at this level, the PACU nurse should have a better understanding of the consequences of employing local anesthetics in regional anesthesia. PMID- 1735872 TI - Change, conflict, and coping. AB - Managing in a health care organization requires the ability to cope with a constantly changing environment in which the manager is often caught in a situation of conflict. Developing a broader perspective on the problem and reframing one's thought process allows more opportunity to deal with the issues through logical rather than crisis management. PMID- 1735873 TI - Copying could be costly. AB - Thanks to modern technology, photocopying is quick, easy, and inexpensive. Or is it? One of the largest awards ever made for copyright infringement was levied in a case involving the use of material copied from publications without permission. This article presents a short discussion about US and international copyright protection, fair use, and work for hire. Suggestions for additional information are offered. PMID- 1735874 TI - Family issues: organization issues. PMID- 1735875 TI - Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their implication for cancer hypotheses. AB - BACKGROUND: The phenoxyherbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) has been widely used by professional pesticide applicators in New Zealand since before 1950. Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals. PURPOSE: The objective of this study was to determine whether the blood serum levels of TCDD in a group of professional 2,4,5-T applicators in New Zealand were greater than those of a matched control group not involved in 2,4,5-T spraying. METHODS: Of 548 men employed as professional pesticide applicators in New Zealand from 1979 through 1982, nine were selected who had sprayed pesticides, although not necessarily 2,4,5-T, for at least 180 months. These applicators had sprayed 2,4,5-T for a range of 83-372 months. We measured the blood serum levels of polychlorinated dibenzo-p-dioxins and dibenzofurans, which were substituted with chlorine at the 2,3,7,8 position, in the nine pesticide applicators and in a matched group of nine control subjects. RESULTS: The average serum level of TCDD for applicators was almost 10 times that for the matched control subjects, while the average levels of all other congeners and isomers measured in the two groups did not differ substantially. TCDD levels in eight of the nine applicators were higher than those in the control subjects (mean difference, 47.7 parts per trilion). The variation in TCDD levels among the applicators was related to their duration of work exposure to 2,4,5-T. CONCLUSIONS: On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyherbicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks. PMID- 1735876 TI - Effect of interleukin-2 on biodistribution of monoclonal antibody in tumor and normal tissues in mice bearing SL-2 thymoma. AB - BACKGROUND: Our laboratory demonstrated previously that treatment with a tumor specific, radiolabeled anti-Thy 1 murine monoclonal antibody (MAb) in mice can eradicate a T-cell lymphoma mass, but the doses required were toxic to normal organs. Approaches to increase MAb concentration in tumor tissue versus normal tissue may overcome this problem. Interleukin-2 (IL-2) has been shown to increase capillary permeability, as indicated by extravasation of albumin. PURPOSE: The purpose of this study was to determine whether increased extravasation of MAb at the tumor site might result in selective binding to tumor antigen, increasing localization of radiolabeled MAb at the tumor site. METHODS: We studied the effect of IL-2 on biodistribution of 1A14 MAb (anti-Thy 1.1) in normal AKR/Cum (Thy 1.2+) mice and in AKR/Cum mice bearing SL-2, a spontaneous T-cell lymphoma (Thy 1.1+), compared with biodistribution of albumin in normal mice and biodistribution of the nonreactive G3G6 MAb in tumor-bearing mice. IL-2 was given intravenously in the tail vein in doses of 0, 25,000, 50,000, 100,000, or 200,000 U twice a day for a total of seven doses over 3.5 days. Mice received injections of a mixture of 1A14 MAb (250 muCi/100 micrograms) and albumin or G3G6 MAb (145 muCi/100 micrograms) in a total volume of 200 microL at 12 hours after the last IL-2 dose. RESULTS: In normal mice, IL-2 caused a dose-dependent increase of both radiolabeled MAb and albumin in the spleen, liver, lung, and lymph node, but it spared the brain. In tumor-bearing mice, IL-2 resulted in higher levels of MAb in the tumors 72 hours after receiving injections, with 17.5% and 24.3% of the injected dose per gram of tumor present in the mice pretreated with 100,000 or 200,000 U of IL-2 twice a day for 3.5 days, compared with 13.4% in the controls. In IL-2-treated mice, levels of MAb were greater in the tumors than in critical normal organs; the differences were statistically significant for tumors versus lungs at 24 hours after injection and for tumors versus livers at 48 hours and 72 hours after injection. CONCLUSIONS: These results suggest that pretreatment with IL-2 may lead to enhanced distribution of tumor-specific MAb to the tumor site, compared with normal tissues, thus increasing therapeutic efficacy of radiolabeled MAb. PMID- 1735877 TI - Suppression of anti-interferon alpha-2a antibody formation in patients with mycosis fungoides by exposure to long-wave UV radiation in the A range and methoxsalen ingestion. PMID- 1735878 TI - Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. PMID- 1735879 TI - Human genetics, bioethics, and the law. PMID- 1735880 TI - Use of very-high-dose chemotherapy with autologous bone marrow transplantation in treatment of breast cancer. PMID- 1735881 TI - Dietary factors in colorectal cancer and their possible effects on earlier stages of hyperproliferation and adenoma formation. PMID- 1735882 TI - Congress weighs NIH bid for patent rights to human genes. PMID- 1735883 TI - Tumor virologists' reunion recalls century of research. PMID- 1735884 TI - Mimetics may one day replace peptide antibodies. PMID- 1735885 TI - Lung cancer rates in white males leveling off. PMID- 1735886 TI - Phase I-II trial of erythropoietin in the treatment of cisplatin-associated anemia. AB - BACKGROUND: Cancer patients undergoing chemotherapy with cisplatin-containing regimens often develop anemia. Although the cause is multifactorial, erythropoietin deficiency appears to play an important role. Recombinant human erythropoietin (epoetin) has been reported to be effective in reversing cisplatin associated anemia in animal studies but not in clinical trials. PURPOSE: This pahse I-II clinical trial was designed to assess the safety and efficacy of treatment with epoetin for anemia associated with cisplatin chemotherapy. METHODS: Twenty-one cancer patients treated with cisplatin and manifesting anemia (hemoglobin level less than 110 g/L) received epoetin at escalating doses (25, 50, 100, or 200 U/kg body weight) intravenously five times a week for 4 weeks. RESULTS: Epoetin was well tolerated, and a maximal tolerated dose was not reached. Two patients experienced hypertension, which responded to standard antihypertensive therapy. No dose-dependent severe toxic effects were seen. The increase in hemoglobin levels from baseline on day 1 of the study was statistically significant after 4 weeks of epoetin therapy in the groups receiving 100 U/kg (mean change +/- SD = 19 +/- 13 g/L; P = .03) or 200 U/kg (mean change = 24 +/- 17 g/L; P = .007). A clinical response--an increase in hemoglobin level greater than 10 g/L--was achieved in 12 patients after 4 weeks of treatment. For these responders, the mean increase in hemoglobin level was 25 +/- 3.3 g/L over the level observed at the same time in the chemotherapy cycle preceding epoetin treatment, and this increase was statistically significant (P = .0001). Neither serum erythropoietin level nor hemoglobin level predicted a patient's response to epoetin. CONCLUSIONS: These preliminary findings suggest that epoetin is effective and well tolerated for the reversal of cisplatin associated anemia, with the 100-U/kg and 200-U/kg dose levels offering optimal clinical response. IMPLICATIONS: We are conducting a phase III trial to determine the effect of epoetin on transfusion requirements in patients undergoing chemotherapy. PMID- 1735887 TI - Society and vascular surgery--the need for humanism and research. PMID- 1735888 TI - Accuracy of lower extremity arterial duplex mapping. AB - We performed lower extremity arterial duplex mapping from the aortic bifurcation to the ankle in 150 consecutive patients evaluated for aortic and lower extremity arterial reconstruction and compared lower extremity arterial duplex mapping in a blinded fashion to angiography. On the basis of history, physical examination, and four-cuff segmental Doppler pressures individual lower extremities were classified as normal, isolated aortoiliac disease, infrainguinal disease, and multilevel inflow and outflow disease. For vessels proximal to the tibial arteries, lower extremity arterial duplex mapping was analyzed for its ability to insonate individual arterial segments, detect a 50% or greater stenosis, and distinguish stenosis from occlusion. In the tibial arteries lower extremity arterial duplex mapping was evaluated for its ability to visualize tibial vessels and to predict interruption of tibial artery patency from origin to ankle. Lower extremity arterial duplex mapping visualized 99% of arterial segments proximal to the tibial vessels, with overall sensitivities for detecting a 50% or greater lesion ranging from 89% in the iliac vessels to 67% at the popliteal artery. Stenosis was successfully distinguished from occlusion in 98% of cases. In the tibial vessels lower extremity arterial duplex mapping was better at visualizing anterior tibial and posterior tibial artery segments (94% and 96%) than peroneal artery segments (83%), (p less than 0.001). Overall sensitivities for predicting interruption of tibial artery patency were 90% for the anterior tibial, 90% for the posterior tibial, and 82% for the peroneal. Clinical disease category did not influence in a major way the accuracy of lower extremity arterial duplex mapping in either above-knee or below-knee vessels. PMID- 1735889 TI - Popliteal entrapment as a result of neurovascular compression by the soleus and plantaris muscles. AB - Intermittent claudication may occur in well-conditioned athletes because of an unusual form of popliteal artery entrapment that results from overtraining. These patients complain of calf muscle cramping, rapid limb fatigue, and occasional paresthesias on the plantar surface of the foot when running on inclines or when repetitive jumping is performed. Results of plethysmographic screening tests for popliteal entrapment are positive in these patients. Magnetic resonance angiography and intravenous digital subtraction angiography studies, however, do not demonstrate findings typical of anatomic popliteal entrapment. No evidence exists of aberrant positioning of the popliteal artery in foot neutral positioning, but with forced plantar flexion, the neurovascular bundle is deviated and compressed laterally. Surgical exploration of the popliteal fossa demonstrates no obvious musculotendinous abnormality. Symptoms of claudication and arterial compression are relieved by surgical release of the soleus muscle from its tibial attachments, resection of its fascial band, and resection of the plantaris muscle. PMID- 1735890 TI - Infected femorodistal bypass: is graft removal mandatory? AB - Infected lower extremity bypass grafts have been associated with high rates of limb loss. Traditionally treatment has included graft excision. To compare aggressive local treatment, without graft removal, with more conventional graft excision, we reviewed 38 consecutive patients with 39 infected lower extremity bypasses treated during the last 10 years. The grafts used were prosthetic in 33 cases, vein in 4, and composite in 2. Median follow-up was 2.7 years. Twenty eight infected grafts were treated with either complete (14) or partial (14) graft removal. Nine new grafts were placed. Recurrent infection developed in five cases, and two patients died of complications of graft infection. Ten of 20 limbs at risk were lost. Eleven patients with patent bypasses (4 vein, 2 composite, 5 prosthetic) were treated without graft excision. Treatment of five patients in this group included muscle transposition. Five patients were treated with incision and drainage of abscesses, and one had excision of a persistent sinus tract. One patient underwent major amputation 6.3 years after treatment of graft infection. Limb salvage was significantly higher (p = 0.012, log-rank test) than in patients treated with graft excision. One patient died, and no recurrent infections developed; these were not significant differences compared with those having graft excision. We conclude that aggressive local treatment of infected lower extremity bypass grafts, including drainage, debridement, and muscle transposition may treat infection in selected patients without the need for graft removal and with rates of limb salvage superior to those obtained with excisional therapy. PMID- 1735891 TI - Heparin-induced thrombocytopenia in the newborn. AB - This pilot study was initiated to determine whether heparin-induced thrombocytopenia occurs in the newborn and whether thromboembolic complications in the newborn could be related to heparin-induced thrombocytopenia. Thirty-four infants in whom thrombocytopenia (less than 70,000/mm3) (n = 23), precipitous (30% to 50%) fall in platelet count (n = 5), or thromboses (n = 6) developed while they were receiving heparin were studied. Heparin-associated antiplatelet antibodies were demonstrated in 14 infants by platelet aggregation testing. The average gestational age (29 +/- 6 weeks); birth weight (1300 +/- 945 gm); and platelet count at birth (234,000/mm3 +/- 111,000/mm3) of these 14 infants did not differ statistically from the 20 infants without heparin-associated antiplatelet antibodies. An umbilical artery catheter was inserted in all infants except a single patient from each group. Aortic thrombosis was documented by abdominal ultrasonography in 11 of 13 (85%) infants with heparin-associated antiplatelet antibodies. One patient died with a midgut volvulus before the aorta could be examined. Five aortic thromboses were detected in the 20 infants without heparin associated antiplatelet antibodies. Bleeding was not associated with the heparin induced thrombocytopenia. One patient with previously demonstrated thrombocytopenia and heparin-associated antiplatelet antibodies had recurrent thrombocytopenia when reexposed to heparin; her platelet count recovered after heparin withdrawal. Thus heparin-induced thrombocytopenia does occur in preterm and term infants receiving heparin and is associated with arterial thromboses. Therefore infants receiving any form or amount of heparin must be carefully monitored for heparin-induced thrombocytopenia.1+ PMID- 1735892 TI - Preoperative carotid artery screening in elderly patients undergoing cardiac surgery. AB - The role of preoperative screening for carotid artery disease in elderly patients undergoing cardiac surgical procedures is not clearly established. This prospective study was designed to determine the prevalence of carotid disease in this population and to identify preoperative risk factors for carotid artery stenosis. During a 54-month interval, 1087 patients of a consecutive series of 1184 patients 65 years of age and older who underwent cardiac surgical procedures (91% had coronary artery disease) were evaluated before operation with carotid duplex ultrasonography. The prevalence of disease was 17.0% for 50% or greater stenosis and 5.9% for 80% or greater stenosis. With use of a stepwise, logistic regression model of 12 preoperative variables, five variables were found by multivariate analysis to be significant (p less than or equal to 0.05) predictors of 80% or greater stenosis: female sex, peripheral vascular disease, history of transient ischemic attack or stroke, smoking history, and left main coronary artery disease. If all patients with at least one risk factor were screened, then this model predicts that 95% of patients with 80% or greater stenosis and 91% of patients with 50% or greater stenosis would be identified before operation. The probability of carotid disease in a given patient can also be estimated (range, 5% to 65%). Carotid endarterectomy combined with cardiac surgical procedures was performed on 46 patients who were either symptomatic (16) or had 80% or greater stenosis (30). The overall stroke rate for the 1087 patients was 2.0% (22 patients), and the 30-day mortality rate was 5.2% (56 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735893 TI - Carotid artery replacement in conjunction with resection of squamous cell carcinoma of the neck: preliminary results. AB - Squamous cell carcinoma can invade the carotid artery. The treatment options then include irradiation, "palliative peeling" of tumor from the artery, and carotid resection with ligation or in-line grafting. Twelve patients with invasion of the carotid artery by cancer had en bloc resection of the artery and tumor. Reconstruction after in-line carotid artery grafting with autogenous vein was completed with a myocutaneous flap. No neurologic events occurred perioperatively or during the follow-up period of 3 to 50 months. Computed tomography and arteriography were unreliable in predicting tumor involvement of the carotid artery. Three patients died during the study--two of unrelated causes, and one of metastases. None of the patients showed evidence of local recurrence from 3 to 50 months. In two of four wound infections the carotid artery graft was exposed. This was successfully treated by a myocutaneous flap. The mean survival for the group was 18 months. Resection and in-line bypass grafting of the carotid artery invaded by cancer can safely be performed in irradiated and potentially infected fields. PMID- 1735894 TI - Acute traumatic aortic aneurysm: the Duke experience from 1970 to 1990. AB - Improvements in the operative management of acute traumatic thoracic aortic aneurysm have resulted in safe and expeditious repair. Nonetheless, multisystem injuries continue to inflict significant numbers of deaths. From 1970 to 1990, 108 patients with acute traumatic thoracic aortic aneurysm were evaluated. Mean injury severity score, excluding aortic injury, was 17.5. Ninety-three patients (86%) survived beyond initial resuscitation and came to operation. Median interval from injury to aortic repair was 8 hours (range, 2 hours to 19 days); there were five operative deaths. Lethal nonaortic injuries included 18 closed head injuries, four myocardial contusions, two intraabdominal vascular injuries, and one pulmonary contusion. The overall mortality rate was 39% of total admissions (42 of 108), and 29% of survivors of resuscitation (27 of 93). It is significant that only 11 of the 42 deaths (26%) were directly attributable to thoracic aortic aneurysm. Adjuncts to prevent spinal cord ischemia (shunt/bypass) were used in 76 patients, whereas 12 underwent clamp/repair. Postoperative paraplegia developed in 5 of 79 patients (6.8%, including 4 of 68 (5.9%) repaired with shunt/bypass and 1 of 11 (9.1%) repaired with clamp/repair (p = NS). Among those who developed paraplegia, the injury severity score was 27.0, and the median interval from injury to repair was 4.9 hours (range, 2 to 6.5). Intraoperative hypotension occurred in three of five patients with paraplegia. Death in patients with thoracic aortic aneurysm is due primarily to associated injuries and has remained relatively constant over the 20-year period of review. Overall injury severity, intraoperative hypotension, and extensive aortic tissue destruction may correlate with the development of postoperative paraplegia; however, a larger population sample is required to confirm this conclusion. A plea is made for standardized reporting of all patients with thoracic aortic aneurysm. PMID- 1735895 TI - Intraabdominal paraanastomotic aneurysms after aortic bypass grafting. AB - Although the reported incidence of intraabdominal paraanastomotic aneurysms after abdominal aortic bypass grafting ranges from 1% to 15%, the true incidence is unknown because few studies have used routine, serial radiographic or sonographic imaging studies. Since July 1, 1988, we have used yearly abdominal sonography examinations to monitor our patients with aortic grafts. In the first 33 months we studied 138 patients. Medical records of 111 of these were available for review and form the basis of this report. Eleven patients (10%) were found to have intraabdominal paraanastomotic aneurysms ranging in overall size from 4.1 to 6.2 cm (mean, 5.0 +/- 0.7 cm). The mean time between operation and detection of an aneurysm was 144 +/- 101 months (range, 8 to 336 months). Three paraanastomotic aneurysms occurred within 3 years of operation, and the remaining eight occurred late (7 to 28 years). By life-table analysis, the incidence of paraanastomotic aneurysms was 27% at 15 years. Paraanastomotic aneurysms were classified as either pseudoaneurysms (presumed disruption of the anastomotic suture line, n = 7) or as true aneurysms (widening of the adjacent aorta, n = 4). True aneurysms occurred only after repair of an abdominal aortic aneurysm, whereas pseudoaneurysms were more frequent after bypass for occlusive disease. The finding of paraanastomotic aneurysms in 10% of our patients supports the use of yearly sonography for routine follow-up after aortic grafting. PMID- 1735896 TI - Comparison of cardiac morbidity between aortic and infrainguinal operations. Study of Perioperative Ischemia (SPI) Research Group. AB - We prospectively compared the differences in perioperative cardiac ischemic events in 140 patients undergoing major abdominal (n = 53) versus infrainguinal (n = 87) vascular operations. Preoperative dipyridamole thallium cardiac scintigraphy was performed in a subset of 38 of these patients, with treating physicians blinded to the test results. Myocardial ischemia was measured during operation with use of continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography. Continuous two-lead ambulatory ECG (Holter monitoring) was performed before, during, and after operation for 4 days. Outcome events were cardiac death, nonfatal myocardial infarction, unstable angina, ventricular tachycardia, and congestive heart failure. Results of the study indicated that most demographic variables, such as age, hypertension, cigarette smoking, serum cholesterol, were comparable between patients having aortic or infrainguinal arterial operations. However, in the infrainguinal group more patients had diabetes, second vascular operations, angina pectoris, heart failure, dysrhythmias, and used digitalis. Abnormalities in preoperative Holter monitoring, ECGs, and thallium scan abnormalities were equivalent between groups. During operation, whereas Holter and ECG abnormalities were comparable, more patients undergoing aortic procedures suffered ischemia as determined by transesophageal echocardiography (26% vs 10%, p = 0.019). After operation there were 21 (24%) outcome events in patients having infrainguinal bypasses compared with 15 (28%) patients having aortic procedures (p = NS). Ischemia by Holter monitoring (n = 133) occurred after operation in 46 (57%) patients having infrainguinal operations compared with 16 (31%) patients having aortic reconstructions (p = 0.005). Because preoperative cardiac disease and adverse cardiac outcomes occurred with similar or even greater frequency in both groups of patients, we conclude that the risk for postoperative cardiac ischemic events in lower extremity vascular operations is at least as great as for aortic operations. PMID- 1735897 TI - Color-flow duplex scanning for the surveillance and diagnosis of acute deep venous thrombosis. AB - Compared with conventional duplex imaging, color-flow scanning facilitates the identification of veins (especially below the knee), decreases the need to assess Doppler flow patterns and venous compressibility, and allows veins to be surveyed longitudinally. These advantages translate into a less demanding and time consuming examination. This study was designed to determine the accuracy of color flow scanning for detecting acute deep venous thrombosis in patients in whom the diagnosis is clinically suspected and in asymptomatic patients at high risk for developing postoperative deep venous thrombosis. The diagnostic group included 77 limbs of 75 patients, and the surveillance group included 190 limbs of 99 patients undergoing total hip or knee replacement. All patients were prospectively examined with color-flow scanning and phlebography. In the diagnostic group, the incidence of thrombi in below-knee veins (47%) was approximately equal to that in above-knee veins (43%); but in the surveillance group, the incidence of thrombi in below-knee veins (41%) far exceeded that in veins above the-knee (3%). Nonocclusive clots and clots isolated to a single venous segment were more common in the surveillance group. In symptomatic patients, color-flow scanning was 100% sensitive and 98% specific above the knee and 94% sensitive and 75% specific below the knee. In the surveillance group, color-flow scanning was significantly (p less than 0.001) less sensitive (55%) for detecting thrombi, 93% of which were confined to the tibioperoneal veins. Negative predictive values were 100% and 88% for the diagnostic and surveillance limbs, respectively. Positive predictive values were 80% for the diagnostic limbs and 89% for the surveillance limbs. Color-flow scanning effectively excludes above-knee deep venous thrombosis in symptomatic patients and asymptomatic high risk patients and predicts the presence of above-knee thrombi in patients in the diagnostic group with reasonable accuracy (97%). We conclude that color-flow scanning is as accurate as conventional duplex imaging and, because of its advantages, is the noninvasive method of choice for evaluating patients with suspected deep venous thrombosis. Its role in the surveillance of patients at high risk remains to be determined and awaits further clinical evaluation. PMID- 1735898 TI - Valvular reflux after deep vein thrombosis: incidence and time of occurrence. AB - From December 1986 to December 1990, 268 patients with acute deep vein thrombosis were studied in our laboratory. From this group 107 patients (123 legs with deep vein thrombosis) were placed in our long-term follow-up program. The documentation of valvular reflux and its site was demonstrated by duplex scanning. The duplex studies were done at intervals of 1 and 7 days, 1 month, every 3 months for the first year, and then yearly thereafter. The mean follow-up time for these patients was 341 days. In addition, reflux was evaluated in 502 patients with negative duplex study results and no previous history of deep vein thrombosis or chronic venous insufficiency. In the patients with acute deep vein thrombosis, valvular incompetence was noted in 17 limbs (14%) at the time of the initial study. Reflux was absent in 106 limbs (86%). In this last group reflux developed in 17% of the limbs by day 7. By the end of the first month, 37% demonstrated reflux. By the end of the first year, more than two thirds of the involved limbs had developed valvular incompetence. The distribution of reflux at the end of the first year of follow-up was the following: (1) popliteal vein, 58%; (2) superficial femoral vein, 37%; (3) greater saphenous vein, 25%; and (4) posterior tibial vein, 18%. Reflux seems to be more frequent in the segments previously affected with deep vein thrombosis. Among cases where segments were initially affected with thrombi, after 1 year the incidence of reflux was 53%, 44%, 59%, and 33% for the common femoral vein, superficial femoral, popliteal vein, and posterior tibial vein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1735899 TI - Surgical management of severe acute lower extremity ischemia. AB - Seventy-four patients (70 men [95%], 4 women [5%], mean age, 63 years) with severe, acute lower limb ischemia (acute clinical deterioration and absent pedal Doppler signals) caused by either arterial thrombosis (n = 68) or embolism (n = 6) underwent urgent surgical management consisting of operative revascularization with or without amputation in 67 patients (91%) and primary amputation alone in 7 patients (9%). Sixty-one patients (82%) had severely threatened limb viability, and 13 (18%) had major irreversible ischemic limb changes at presentation. Eighty six percent of patients were initially anticoagulated with heparin. Seventy percent underwent preoperative angiography. Surgical revascularization included 42 inflow and 20 outflow arterial reconstructions and 9 thrombectomy or embolectomy procedures. Mean follow-up was 17 months (range, 0 to 64). Life-table primary patency at 36 months for arterial reconstructions was 81% for inflow and 78% for outflow procedures. Cumulative limb salvage was 70% at 1 month and 68% at 36 months. Patient survival was 85% at 1 month and 51% at 36 months. No death was directly attributable to complications related to limb reperfusion, and no patient required dialysis for myoglobinuria. We conclude that management of severe, acute lower limb ischemia with early amputation of nonviable limbs and heparinization, angiography, and prompt operative revascularization for threatened but viable extremities minimizes morbidity and mortality rates, while maximizing limb salvage. These results may be useful for comparison with comparable groups of patients treated with thrombolytic or endovascular modalities. PMID- 1735900 TI - Peripheral vascular bypass in juvenile-onset diabetes mellitus: are aggressive revascularization attempts justified? AB - This study was performed to evaluate the results of peripheral vascular reconstruction for arterial occlusive disease in patients with juvenile-onset diabetes mellitus. The results of 67 bypass procedures performed on 60 patients with juvenile-onset diabetes mellitus between Jan. 1, 1984 and Dec. 31, 1989, were reviewed. These patients had a mean age of 44.4 years (range, 29 to 59 years), with an average age of onset of diabetes mellitus of 9.8 years (range, 1 to 19 years). These procedures comprised 5.5% (67 to 1214) of the bypasses performed on diabetic patients during the same time period at a single institution. Fifty-four of 67 (91%) procedures were performed for limb salvage. Fifty-four (81%) procedures were primary infrainguinal bypasses with saphenous vein (femoropopliteal 19, femorodistal or popliteal-distal 35). Six procedures (9%) were revision procedures, four (6%) were in-flow procedures, and three (4%) were infrainguinal procedures with polytetrafluoroethylene. Thirty-day morbidity and mortality rates were 31% and 0%, respectively. Actuarial patency and limb salvage rates of the primary vein graft group were 66.0% (+/- 10.7) and 83.4% (+/ 8.0%), respectively, at 24 months. Cumulative survival of the entire group at 2 years was 84.1%. Although follow-up in this study is relatively short (24 months), the results suggest that the outcome of vascular reconstruction in patients with juvenile-onset diabetes mellitus is acceptable when compared with procedures performed in adult-onset diabetic and nondiabetic populations. The presence of juvenile-onset diabetes mellitus should not diminish the vascular surgeon's expectations of a successful outcome when considering lower extremity revascularization in these patients. PMID- 1735901 TI - Is long vein bypass from groin to ankle a durable procedure? An analysis of a ten year experience. AB - Long vein bypass from the femoral artery to the level of the ankle may be performed with good initial success despite extreme bypass length and limited outflow tracts. However, the long-term performance of these bypasses remains to be defined. During the last 10 years we have performed single greater saphenous vein in situ bypass to the ankle level in 270 patients. There were 187 male and 83 female patients, and 61% of the patients were diabetic. The operative mortality rate was 3.7%. Cumulative bypass patency was 79% at 3 years and 73% at 5 years. In a similar manner, limb salvage was 93% at 3 years and 89% at 5 years. The patency rate was similar for various inflow arteries (common femoral, 88 cases; proximal superficial femoral, 135 cases; and deep femoral, 41 cases) and outflow tracts (dorsal pedal, 72 cases; anterior tibial, 59 cases; posterior tibial, 72 cases, and peroneal, 67 cases). Short bypasses, composite bypasses, free-vein grafts, and bypasses proximal to 10 cm above the ankle were excluded from this analysis. These data show that a long bypass to the ankle level for limb salvage is a durable procedure. The basic concept of bypassing all occlusive disease to the distal open artery in patients undergoing limb salvage should be an acceptable dictum. Excellent long-term patency and limb salvage rates are achievable by following this principle. PMID- 1735902 TI - The dorsalis pedis bypass--moderate success in difficult situations. AB - Recent reports have documented excellent results for inframalleolar reconstructions. We reviewed our outcomes for dorsalis pedis bypass and report a more modest rate of success. We analyzed reasons for failure. Sixty-nine patients underwent 73 dorsalis pedis bypass procedures between 1984 and 1991. Seventy eight percent of the patients were diabetics. Inflow was from the external iliac in 1, femoral in 35, popliteal in 34, and tibial in 3. The operative indication was gangrene in 57%, ulcer in 22%, and rest pain in 21%. Forty-six percent of limbs had foot infection, with six requiring minor amputation before the bypass and 24 requiring minor amputation after bypass. There was one perioperative death. Twenty-nine grafts failed over the course of the series. The primary patency rate at 2 years was 59.2%. The limb salvage rate was 73.5%. Of the 10 perioperative failures, four were due to continued foot infection, four to marginal vein quality, and two to skin necrosis of the bypass incisions. Graft failure occurred at 3 to 30 months in 10 of 14 patients who had deficient anterior arches, with segmental occlusion of the dorsalis pedis or its branches. Six of the 14 patients with extensive infections of the forefoot or extensive heel ulcers required amputation with patent bypasses. In dorsalis pedis bypass, failure to achieve limb salvage was more likely in patients with marginal vein quality, deficient anterior pedal arches, and extensive foot infection. In patients where the chance of failure appears to be unacceptably high, primary amputation should be considered. PMID- 1735903 TI - The seventh John Homans Lecture: heroes in vascular surgery. PMID- 1735904 TI - Dissecting aneurysms of the main trunk of the superior mesenteric artery. AB - We treated four symptomatic patients who were admitted with a spontaneous and isolated dissecting aneurysm of the superior mesenteric artery. All four patients underwent operation. The superior mesenteric artery was repaired by means of either a bypass graft in two cases or an endoaneurysmorraphy in the latter two cases. Complete symptomatic relief with no postoperative complications was achieved in every case. The arterial repairs remained patent, and the patients remained free of symptoms, with follow-up ranging from 6 to 47 months. The available literature on this unusual lesion is reviewed. PMID- 1735905 TI - Bilateral traumatic internal carotid artery dissections: case report. AB - Bilateral internal carotid artery dissections after blunt cervicofacial trauma are rare, with 16 cases being previously published. Management is presumed to be an extension of the dominant therapy for unilateral dissection, that being anticoagulant therapy; however, bilateral stenoses engender questions of threat to total cerebral blood flow. We herein present a patient who suffered bilateral type B dissections and who then had progression of the process on anticoagulant therapy, resulting in an unusual carotid reconstruction. PMID- 1735906 TI - Renal autotransplantation in the management of a ureteroarterial fistula: a case report and review of the literature. AB - A 57-year-old woman who had been treated with an indwelling ureteral stent for over a year was admitted with massive gross hematuria caused by a fistula between the left ureter and hypogastric artery. Despite intensive radiographic evaluation, the definitive diagnosis was made only at the time of surgical exploration. Because of radiation-induced retroperitoneal fibrosis, midureteral obstruction, and prior pelvic and abdominal surgery, primary ureteral repair was not possible, and renal autotransplantation was performed. This case illustrates the need to consider the diagnosis of ureteroarterial fistula in patients with massive hematuria who have chronic indwelling stents, and the feasibility of autotransplantation when primary ureteral repair is not feasible. PMID- 1735907 TI - Fourth annual meeting of the American Venous Forum, Coronado, California, February 26-28, 1992. Abstracts. PMID- 1735908 TI - Ruptured abdominal aortic aneurysm: an editorial. PMID- 1735909 TI - Cells derived from omental fat tissue and used for seeding vascular prostheses are not endothelial in origin. PMID- 1735910 TI - Cocaine, alcohol mix in body to form even longer lasting, more lethal drug. PMID- 1735911 TI - Infants, children test positive for cocaine after exposure to second-hand crack smoke. PMID- 1735912 TI - Cocaine deaths reported for century or more. PMID- 1735914 TI - From the Centers for Disease Control. Vigorous physical activity among high school students--United States, 1990. PMID- 1735913 TI - From cell populations to human populations, cardiovascular research examines possibilities. PMID- 1735915 TI - From the Centers for Disease Control. International task force for disease eradication. PMID- 1735916 TI - From the Centers for Disease Control. Iguana-associated salmonellosis--Indiana, 1990. PMID- 1735917 TI - Red cell distribution width in alcohol abuse and iron deficiency anemia. PMID- 1735918 TI - Red cell distribution width in alcohol abuse and iron deficiency anemia. PMID- 1735920 TI - Ads from the Partnership for a Drug-Free America. PMID- 1735919 TI - Relation between serum cholesterol and hematocrit. PMID- 1735921 TI - Cost-shifting in Oregon. PMID- 1735922 TI - Potential therapeutic effects of ritanserin in Cushing's disease. PMID- 1735923 TI - Bury me as a pipe smoker. PMID- 1735924 TI - Compliance with live, oral Ty21a typhoid vaccine. PMID- 1735925 TI - Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men. AB - OBJECTIVE: To investigate the patterns of electrolyte abnormalities resulting from thiazide administration and whether they cause ventricular arrhythmias, and to help resolve the controversy over whether clinicians should routinely prescribe potassium-conserving therapy to all patients treated with thiazides. DESIGN: Double-blind, randomized controlled trial. PARTICIPANTS: A total of 233 hypertensive men aged 35 to 70 years. INTERVENTIONS: Participants were withdrawn from prior diuretic treatment and were replenished with oral potassium chloride and magnesium oxide. They were then randomized to 2 months of treatment with (1) hydrochlorothiazide; (2) hydrochlorothiazide with oral potassium; (3) hydrochlorothiazide with oral potassium and magnesium; (4) hydrochlorothiazide and triamterene; (5) chlorthalidone; or (6) placebo. MAIN OUTCOME MEASURES: Ventricular arrhythmias on 24-hour Holter monitoring and serum and intracellular potassium and magnesium levels. RESULTS: Of the 233 participants, 212 (91%) completed the study. Serum potassium levels were 0.4 mmol/L lower in the hydrochlorothiazide group than in the placebo group (P less than 0.01), and this mean difference was not affected by supplementation with potassium, with potassium and magnesium, or with triamterene. However, the supplements did prevent the occasional occurrence of marked hypokalemia; all 12 of the men who developed serum potassium levels of 3.0 mmol/L or less were among the 90 who received diuretics without supplementation (P less than 0.01). Similarly, the overall proportion of men with ventricular arrhythmias was not affected by randomized treatment, but there was a twofold increase in the proportion with arrhythmias among the 12 men with serum potassium levels of 3.0 mmol/L or less (P = .02). Serum magnesium and intracellular potassium and magnesium levels were not reduced by hydrochlorothiazide, nor were they related to ventricular arrhythmias. CONCLUSIONS: In the majority of hypertensive patients, treatment with 50 mg/d of hydrochlorothiazide does not cause marked hypokalemia or ventricular arrhythmias. However, because some individuals will develop hypokalemia after starting diuretic therapy, serum potassium levels should be monitored and potassium sparing strategies should be used when indicated. PMID- 1735926 TI - Incidence of lymphomas and other cancers in HIV-infected and HIV-uninfected patients with hemophilia. AB - OBJECTIVE: To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). DESIGN: Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. SETTING: Fifteen hemophilia treatment centers. PATIENTS: A total of 1701 patients with hemophilia, of whom 1065 (63%) were HIV-1 seropositive. MAIN OUTCOME MEASURES: Morphologic classification and incidence rates of cancers. MAIN RESULTS: The incidence of non-Hodgkin's lymphoma after HIV seroconversion averaged 0.15 case per 100 person-years (95% confidence interval [CI], 0.08 to 0.25) and rose exponentially with increasing duration of HIV infection. Although the greatest absolute risk of lymphoma was in the oldest age group, the relative increase compared with general population rates was 38-fold in subjects 10 to 39 years old and 12-fold in older subjects (P less than .05). The CD4+ T-lymphocyte levels for lymphoma cases were similar to HIV-positive subjects without the acquired immunodeficiency syndrome (AIDS) who had been infected for the same length of time. The incidence of Kaposi's sarcoma was increased 200-fold (95% CI, 20 to 700). The incidence of cancers other than non Hodgkin's lymphoma and Kaposi's sarcoma were not increased in the HIV-positive subjects (ratio of observed to expected cases, 0.9 [95% CI, 0.4 to 1.9]). The HIV negative subjects had no significant increase in cancer incidence. CONCLUSIONS: HIV infection has restricted effects on cancer incidence that are only partly explained by immunosuppression. Paradoxically, improvements in therapy of HIV infection that prolong survival may lead to further increases in HIV-associated lymphoma. PMID- 1735927 TI - Delayed diagnosis of infants with abnormal neonatal screens. AB - OBJECTIVE: To identify infants who were diagnosed clinically with a condition that previously had been detected by a state neonatal screening program, but who had failed to receive medical attention in a timely fashion. DESIGN: A descriptive case series of infants over a 2-year period from 1989 to 1991. SETTING: An academically affiliated tertiary care pediatric hospital, a major referral center for children with abnormal results on state neonatal screening tests. PATIENTS: All patients who (1) had a diagnosis suspected clinically, (2) had confirmation of disease, and (3) were subsequently found to have had abnormal screening results. MAIN OUTCOME MEASURES: Age at clinical diagnosis, morbidity due to delay in diagnosis, and postnatal medical follow-up. RESULTS: Ten children were identified, three with 21-hydroxylase deficiency and seven with a hemoglobinopathy. In each case, the screening program had clear documentation that the office of the physician of record had received prompt telephone communication of the abnormal result. The mean age at clinical diagnosis was 32 days for the children with 21-hydroxylase deficiency and 215 days for those with sickle cell anemia, substantially longer than is mandated by proper neonatal screening practice. Potentially life-threatening complications of the underlying disease were present in six children. CONCLUSIONS: A significant number of neonates who have metabolic disorders appropriately identified by a neonatal screening test may fail to receive timely treatment. Consideration should be given to implementing a system of directly contacting the parents of all presumptive positive cases by the state screening program. PMID- 1735928 TI - High prevalence of recent cocaine use and the unreliability of patient self report in an inner-city walk-in clinic. AB - OBJECTIVE: To determine the prevalence of recent cocaine use and the reliability of patient self-reported cocaine use. DESIGN: A survey with blinded comparison to a criterion standard. SETTING: Walk-in clinic of a large public hospital in metropolitan Atlanta, Ga. PARTICIPANTS: Male patients, aged 18 to 39 years, presenting to the triage desk for immediate care during weekdays. Of the 415 eligible men who agreed to participate (acceptance rate, 82%), the average age was 29.5 years, 91.6% were black, and 89% were uninsured. INTERVENTION: None. MAIN OUTCOME MEASURES: Comparison of self-reported illicit drug use with results from urinary immunoassays for benzoylecgonine, a major cocaine metabolite. Determination of which drug history questions produce the most accurate responses using anonymous urine testing as the criterion standard. RESULTS: Thirty-nine percent of patients tested positive for the presence of benzoylecgonine and were statistically more likely to be older, black, and have a prior history of sexually transmitted disease (P less than .01). Seventy-two percent of men with positive urinary assays denied illicit drug use in the 3 days prior to sampling. When queried with several formats, subjects with positive urine assays were more likely to admit to "any illegal drug" use (87.5%) than to the more specific "any form of cocaine" use (60.6%) within the prior year (P less than .0001). CONCLUSIONS: These results underscore the magnitude of cocaine abuse among black, inner-city men. Patient self-report of illicit drug use is highly inaccurate. Accuracy of self-report may be increased by asking less specific questions. PMID- 1735929 TI - The uninsured and the debate over the repeal of the Massachusetts universal health care law. AB - OBJECTIVES: The debate in Massachusetts over the repeal of the first state-based "pay or play" universal health plan is discussed using data from a survey of 1066 Massachusetts households. The survey attempted to measure the problems of the uninsured, to estimate the likelihood that they would buy insurance if offered, and to calculate the proportion of the uninsured who would be covered under an employer mandate. DESIGN: A survey conducted in person and by telephone in 1066 households, with an oversample of uninsured households, using stratification, clustering, disproportionate sampling, and poststatistical weighting. PARTICIPANTS: Adults aged 18 years and older who were knowledgeable about the insurance status of persons in their household. MAIN OUTCOME MEASURES: Insurance status, employment status, access to and use of health services, and willingness to purchase health insurance. RESULTS: First, the present system of hospital based uncompensated care in Massachusetts is inadequate by itself to meet the needs of uninsured residents. Uninsured persons are less likely than insured ones to seek medical care for chronic health problems and serious symptoms requiring evaluation. Second, 83% of uninsured families and 24% of uninsured individual respondents would purchase one of several insurance options with 30% of the cost subsidized. Last, the employer mandate provisions of the legislation would cover 43% of the uninsured in Massachusetts. CONCLUSION: In the current economic climate, the political viability of the universal health care plan and similar national initiatives is uncertain given the intractable conflict between perceptions of the financial stability of small businesses that do not offer insurance and the health care needs of uninsured individuals. PMID- 1735930 TI - Informed consent in tests of patient reliability. PMID- 1735931 TI - Improvement of optic nerve head appearance after surgery for pseudotumor cerebri. PMID- 1735932 TI - [Nd-YAG laser therapy of tracheobronchial lesions by malignant tumor]. AB - Thirty-seven patients with tracheobronchial lesions by malignant tumor were treated with Nd-YAG laser. Thirty-seven patients were twenty-three males and fourteen females and ages ranged from 34 to 79 years. Diseases included were primary tracheal tumor in 3 cases, lung cancer in 16 (8 squamous cell carcinoma, 5 adenocarcinoma, 2 large cell carcinoma, 1 small cell carcinoma), cancer of adjacent organs in 9 (5 thyroid cancers, 4 esophageal cancers), and metastatic cancer to the lung or mediastinal lymph nodes in 9 (4 renal cell carcinoma, 2 thyroid cancer, one patient respectively, colon cancer and breast cancer). Intermittent irradiation of YAG laser was done for 0.5 second at 30-40 Watt through flexible bronchoscope under local anesthesia. It was repeated 1 to 41 times (mean 4.1 times) and energy amount was 148 Joules to 18,513 Joules (mean 3,305 J). The result was; stenosis disappeared in 22 cases (59.4%), improved in 14 (37.8%), and in one case YAG laser therapy discontinued due to intractable bleeding. The Nd-YAG laser therapy for tracheobronchial lesions by malignant tumor is very useful to improve dyspnea or atelectasis. PMID- 1735933 TI - [Nd-YAG laser treatment of tracheo-bronchial stenotic lesions]. AB - Fourteen patients were treated with a Nd-YAG laser. Treatment to relieve airway stenosis was administered on fifteen occasions, and on one occasion to treat an obstruction. In each case the flexible fiberoptic bronchoscope was used. In 4 emergency cases, three involving tracheal lesions and one involving a bronchial lesion, the airway was widened and the patients' condition was improved after laser ablation. In the palliative treatment of 12 lesions, the stenoses were severed and treated at an interval of time varying between one and three weeks. Complications occurred in 3 cases. There were 2 instances of massive haemorrhage and one of pneumothorax which occurred while treating the 5 stenoses situated at broncho-plastic anastomoses. PMID- 1735934 TI - [YAG laser therapy of central airway stenosis]. AB - Endoscopic Nd-YAG laser therapies were performed in 11 cases of central airway stenosis. There were 5 cases of malignant tumor and 6 cases of benign disease. Three cases underwent emergency procedure, and all cases got benefit. In 2 cases they were performed for preoperative preparation, and effective in all cases. In 6 cases with benign stenosis they were performed for airway dilation, and effective in 2 cases, non-effective in 3, and could be evaluated in one. We concluded that endoscopic Nd-YAG laser irradiation was effective for emergency procedure and preoperative preparation. Non-effective cases were 2 cases of post bronchoplasty and 1 case of post Lineac irradiation. And there was no indication of Nd-YAG therapy in the lesions developing longitudinally for long distance and with deformities of cartilaginous ring, and those without information of distal airway from stenosis. PMID- 1735935 TI - [Endoscopic Nd-YAG laser treatment of tracheobronchial lesions]. AB - Eight cases treated with Nd-YAG laser via fiberoptic bronchoscopy were studied. Four of them were primary lung cancer, one was tracheal invasion of thyroid cancer and three were postintubation lesions of trachea. In six cases, Nd-YAG laser treatment was effective for enlargement of the airway lumen and improvement of their symptoms. In the cases of advanced lung cancer, not only local findings of the tumor but also clinical stage and possibility of adjuvant therapy must be considered to apply this procedure. In the cases of postintubation tracheal stenosis (except polypoid lesions), T-tube stenting or surgical reconstruction must be followed after laser treatment. Nd-YAG laser treatment can be useful for the tracheobronchial lesions such as primary tracheal tumors, lung cancer, metastatic tumors, postintubation tracheal stenosis and so on if applied precisely. PMID- 1735936 TI - [Laser vaporization for tracheobronchial lesions using a double intubation technique under general anesthesia]. AB - A method for simple and safe management of laser vaporization is described. Following intubation with a thin endobronchial tube which is removed from a twin lumen tube, a thick endotracheal tube for a bronchial fiberscope is intubated. This double intubation technique provides for a safe and long operation without danger of vapor inhalation. PMID- 1735937 TI - [Use of airway stent subsequent to endoscopic Nd-YAG laser treatment in central airway obstruction]. AB - Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state. PMID- 1735938 TI - [Therapeutic application of Nd-YAG laser treatment for the chest surgery area]. AB - Laser therapy is now a well-established procedure and an accepted method of treatment in thoracic surgery. Therefore, using Nd-YAG laser (Model Md-50 Y) at hospital, we had discussed for the technique and its indication of laser therapeutic application against chest diseases. The following results were obtained; 1) The first object of endoscopic laser therapy is to keep the normal air-way from tracheobronchial stenosis or its bleeding as fast as possible. 2) As this laser techniques are not only the quick expansion of the residual lung but also relative absence of air-leak and blood loss, they are indicated for open lung biopsy or partial resection of metastatic lung tumors, particularly in patients with poor pulmonary function. 3) In conjunction with standard surgical technique of chest surgery, this laser treatment provides numerous other possibilities which facilitate the achievement of the therapeutic goal of surgical operation on the lungs. PMID- 1735939 TI - [Endoscopic Nd-YAG laser therapy and tracheobronchial surgery]. AB - We applied endoscopic Nd-YAG laser therapy to eight cases before the tracheobronchial surgery (six lung cancers and two metastatic tracheal tumors). The preoperative application of Nd-YAG laser is a useful choice for the release of air way stenosis, the defining the border of tumor extension and the securing endotracheal intubation for anesthesia. More cases come into the category of surgical indication when Nd-YAG laser is applied, combined with chemotherapy and/or radiation. Preoperative evaluation of the limit of tracheobronchial resection as well as the method of the reconstruction are essential, however, the precise line of the dissection should be determined by knowing the histological finding of the resected by during the operation to make sure of the operative radicality. PMID- 1735940 TI - [The advantages of laser assist in parenchyma-sparing pulmonary resection]. AB - The advantages of laser irradiation were investigated retrospectively, using a total of 89 parenchyma-sparing pulmonary resection (PSPR) for localized lung lesions which included 42 conventional wedge resection (CWR), 8 PSPR using electrocoagulator (PE) and 39 PSPR using CO2 laser or Nd:YAG laser (PCYL). The major axes of the lesions in PNYL (25.4 +/- 10 mm) were significantly (p = 0.0387) longer than that in CWR (20.3 +/- 11.3 mm). The amount of bleeding during operation was similar in three groups. The mean value of the amount of postoperative exudation from the thoracic drains in PCYL (615 ml) was only 60 ml more than that in CWR. Bloody sputum was observed for 4.8 days in PCYL and 5.0 days in CWR, whereas 7.1 days in PE. Air leak was observed 33.3% in PCYL, 37.5% in PE, whereas 22.5% in CWR, that continued for 1.7 days (mean value) in PCYL, 1.6 days in PE and 2.0 days in CWR. Decrease (differences between preoperative and postoperative lung functions/volume of the lesions) in FVC and FEV1.0 in PCYL (mean values = 221, 158) and PE (174, 135) were less than that in CWR (339, 204). Laser assist in PSPR revealed advantages in hemostasis comparing with PE, and in parenchyma-sparing comparing with CWR. And no clear difference between PCYL and CWR in bleeding during operation, the amount of postoperative exudation and postoperative air leak. CO2 laser is reported that has higher potential in vaporization or cutting but lower ability in hemostasis comparing with Nd:YAG laser, so authors would express that Nd:YAG laser assist is most safe and effective in parenchyma-sparing lung resection. PMID- 1735941 TI - [Usefulness of Nd-YAG laser for the excision of multiple lung metastases and segmentectomy for primary lung cancer]. AB - Since 1986, limited resection of 561 pulmonary metastases in 25 patients was performed with the neodymium:yttrium-aluminum-garnet (Nd-YAG) laser. Use of the laser enabled a local excision of both superficially located and deep-seated tumors that would otherwise have required segmentectomy or lobectomy for safe removal. As a result, the 5-year survival rate for these patients was 40.3%. Since 1988, we also developed laser segmentectomy to treat primary lung cancer, and performed this procedure on 25 lung cancer patients. Of those, twenty-one patients had T1N0 disease. All are alive now and have had no local recurrence. The pulmonary distortion, which leads to impairment and loss of pulmonary function, was minimal in laser resection when compared to other procedures such as stapled resection or the casual ligation-division technique. In conclusion, we have found the Nd-YAG laser to be an effective tool both for preserving pulmonary function and for obtaining clear safety margins. PMID- 1735942 TI - [Application of the Nd-YAG laser for surgical resection of pulmonary metastases]. AB - We used Nd-YAG laser equipment for operations on pulmonary metastatic tumors in order to preserve the residual pulmonary functions simultaneously with local curability by utilizing the features of the contact and non-contact types of equipment. The subjects were patients showing no lymph node metastasis in the preoperative diagnosis. The equipment used was Nd-YAG laser model 6,000 with a surgical probe and contact tip attached. Thoracotomy was performed by a method involving minimum invasion in accordance with the tumor localization to prevent reduction of the postoperative respiratory function as much as possible. An incision was made in the pleura and lung using the contact tip with an output of about 25 Watts with the surgical margin separated sufficiently from the tumor, and the tumor was resected. Coagulative hemostasis was apt to occur in the small vessels. To eliminate postoperative hemostasis and residual tumors, non-contact type irradiation was performed at the surgical margin at an output of about 50-70 Watts. Finally, the pleura were sutured. This method has been used so far on 10 cases of pulmonary metastatic tumors, and in all cases, the amount of hemorrhaging during the operation was small, the operating time was short and the postoperative reduction in respiratory function was slight. In cases of bilateral multiple pulmonary metastases, as many as 30 resections were performed, but no recurrences have been seen in any of the cases to date. Although the usefulness of this method still cannot be confirmed because of the small number of cases involved, this method seems promising from the standpoints of local curability and preservation of pulmonary functions. PMID- 1735943 TI - [Application and limitation of laser pulmonary resection]. AB - A new type of laser handpiece, bipolar Nd-YAG laser dissector, was experimentally applied for laser pulmonary resection of the dogs. The lung was completely and easily divided by the use of the bipolar laser dissector without scissors. The dissected edge without cartilages was completely sealed and additional stitches by threads was not required. But massive leakage of air was obvious from the dissected bronchus. The cause of unsuccessful sealing of the bronchus was supposed to be an unequal tissue remodeling, because of a very high melting point of cartilages compared with other tissue. We conclude that the bipolar Nd-YAG laser dissector contributes segmental pulmonary resection at the level without bronchi and it should not be applied for pulmonary resection containing bronchial cartilages. PMID- 1735944 TI - [Application of laser in the treatment of spontaneous pneumothorax and emphysema]. AB - From August 1990 to August 1991, sixteen patients with bullae or blebs (pneumothorax 9, giant bullae 5, bullous emphysema 2) were treated by CO2 laser ablation under limited thoracotomy. We found the irradiation of bullae or blebs by CO2 laser quite effective in eliminating these bullous lesions which were often multiple and inoperable by conventional methods. Histological examination revealed the wall of bullae where CO2 laser was applied became thick with dense fibrous tissues and degenerated collagen fibers which, however, were not disrupted. The procedure was safe and we were able to operate patients with disabling emphysema. Because CO2 laser can penetrate only 0.2-0.3 mm of tissue thickness, it is suitable for the ablation of bullous lesions which have thin walls and rapidly shrink and collapse by irradiation leaving thick walled scar tissues. Removing multiple bullae and blebs in patients with bullous emphysema can improve gas exchange by reducing dead spaces and elevating the diaphragm which is often flat and downward displaced because of hyperinflation in these patients. We are planning to incorporate thoracoscopy for this operation to make the procedure less invasive. PMID- 1735945 TI - [Thoracoscopic laser coagulation shrinkage of blebs in the treatment of spontaneous pneumothorax]. AB - As a thoracoscopic treatment for spontaneous pneumothorax, electrocautery has been mainly used. But contact type electrocautery has a risk of perforation of blebs. We adopted carbon monoxide laser (wave length 5.4 microns) and good coagulation shrinkage of blebs could be obtained by non-contact irradiation. CO laser was delivered by As-S glass fiber and power of fiber tip was 2-4 W. Compared with Nd-YAG laser (wavelength 1.06 microns), CO laser showed lower risk of perforation of blebs. Thoracoscopic CO laser coagulation shrinkage of blebs proved to be a important method of treatment for patient of spontaneous pneumothorax. PMID- 1735946 TI - [Experience of Nd-YAG laser treatment in roentogenographically occult bronchogenic squamous cell carcinoma]. AB - Out of 201 patients with roentogenographically occult bronchogenic squamous cell carcinoma, 165 lesions underwent surgical operations, while 41 lesions underwent non-invasive therapy. The 5-year survival rate including all causes of death, was significantly higher in the surgical operation group than that in the non invasive therapy group (83% vs 43%). Among 14 cases who received Nd-YAG laser treatment, one case died but 4 cases are alive bearing cancer. Since time span of follow-up period is short, it is hard to say that the prognosis of the Nd-YAG laser therapy in fair. Nd-YAG laser treatments were effective for cancers which did not invade beyond bronchial cartilage. From the bronchoscopic examinations and studies with resected lungs, we suggest that Nd-YAG laser treatments may be effective when cancer is extended within 10 mm wide and has only a slight findings in bronchoscopy. PMID- 1735947 TI - [Photodynamic therapy of roentgenographically occult lung cancer]. AB - Between December 1983 and August 1990 25 patients (a total of 29 carcinomas) with roentgenographically occult lung cancer were treated by PDT at National Kinki Central Hospital for Chest Diseases. A complete remission (CR) occurred in 21 carcinomas (72%). Of 19 carcinomas with tumor length of 1 cm or less, 17 ones (89.5%) achieved a CR. Of 21 carcinomas with visible tumor of the peripheral area, 17 ones (85.7%) achieved a CR. Five carcinomas relapsed from 7 to 18 months after PDT. The length of tumor and the visibility of peripheral area of tumor are important factors for CR and relapse. Fourteen patients (56%) had double, triple or quadruple cancers. Until now, 10 patients died. The main causes of death were metachronous secondary cancers and respiratory or heart failure. PDT have a potential to become an alternative to surgical resection as the primary treatment for early stage roentgenographically occult lung cancer. PMID- 1735948 TI - [An experience of laser therapy of lung cancer complicated with hemophilia A]. AB - We applied an endoscopic Nd-YAG laser therapy for an early hilar lung cancer complicated with hemophilia A in a patient of 62-year-old male. Abnormality was pointed out by means of sputum cytology. But, no shadow of tumor was observed by chest x-ray films and computed tomogram. By a bronchoscopy, a mild irregular mucomembrane and stenosis without tumor were exhibited. By means of cytological diagnosis of an abrasive-washing specimen of that region, the presence of squamous cell carcinoma was proved. Also, he was diagnosed as factor VIII deficient hemophilia A. So we performed him a laser therapy in place of the operation and with an intrabronchial arterial infusion. After the laser treatment, the conditions progressed better without any recurrence but about one and a half years later, an intrapulmonary metastasis occurred. Then, radiation and chemotherapy have been applied and at present, the patient is in a good state although under the tumor-bearing condition. PMID- 1735949 TI - [Surgical treatment of arrhythmia]. PMID- 1735950 TI - [Management of airway obstruction using the neodymium-yttrium-aluminium-garnet laser]. AB - The neodymium-yttrium-aluminium-garnet laser (Nd-YAG laser) has proved to be useful therapeutic tool for the management of endobronchial lesions. Between February 1983 and January 1991, 16 patients received endobronchial laser therapy at the Nagasaki University Hospital, 7 patients for tracheal stenosis, and 9 for endobronchial obstruction. In 4 patients with tracheal stenosis, the therapy was performed in an emergency. The type of lesions were lung cancer in 7 patients, thyroid cancer in 3, tracheal tumor (squamous cell carcinoma, and chondrosarcoma) in 2, esophageal cancer in 1, bronchial submucosal tumor in 1, and tracheobronchial tuberculosis in 2. Good symptomatic relief was obtained in 13 patients. One patient died from massive bleeding in the left main stem bronchus. Reobstruction had occurred in 2 patients with cicatricial lesion in right main stem bronchus. In patients with an unresectable malignant lesion, concurrent radiotherapy was needed to prevent the reobstruction. PMID- 1735951 TI - Ewing's sarcoma: new approaches to histogenesis and molecular plasticity. PMID- 1735952 TI - Human natural killer cells: clonally distributed specific functions and triggering surface molecules. PMID- 1735953 TI - Cellular and molecular mechanisms of renal carcinogenesis induced by avian erythroblastosis virus. AB - Besides erythroleukemias and sarcomas, avian erythroblastosis virus strain ES4 (AEV-ES4) induces renal adenocarcinomas (RCas) in chickens. To search for the cells of origin and the mechanism of the development of RCas, we investigated the RCas produced by td359AEV, a mutant of AEV-ES4 which lacks a leukemogenic effect, but which is sarcomagenic. Spindle cell sarcomas in various organs and RCas developed in a high number of chickens inoculated with td359AEV. RCas were tubulo cystopapillary structures of basophilic cells and originated only from differentiated principal cells (PCs) of the renal collecting duct system. The origin of tumors from PCs was indicated by connections of tumor epithelium to segments of the collecting duct system, including connecting tubules and cortical and medullary collecting ducts. Tumor cells showed typical mucopolysaccharide containing vacuoles which are characteristic of chicken PCs. Viral particles were observed throughout the kidney. Moreover, the highest numbers of particles as well as budding-images of them were seen (apart from tumor cells) in podocytes and distal tubule cells which did not undergo neoplastic change. The susceptibility of PCs to undergo neoplastic transformation could not be related to a particular activation state of the erbB gene, in view of the fact that cerbB expression was detected by in situ hybridization in the epithelium lining the Bowmann's capsule and the entire renal tubule system. From data of Northern blot and in situ hybridization techniques, it was suggested that the neoplastic transformation of PCs was elicited by overexpression of the v-erbB oncogene, a feature of tumor cells already detected in renal tubules lined by basophilic proliferating cells, the first stages of renal carcinogenesis induced by td359AEV. According to Southern blot analysis, td359AEV proviruses were randomly inserted in tumor DNAs and the RCas were polyclonal in nature. PMID- 1735954 TI - Neuroendocrine differentiation in adrenocortical carcinoma. New immunohistochemical findings supported by electron microscopy. AB - Ten adrenocortical carcinomas including two tumors with clinically detectable corticosteroid production, were immunohistochemically analyzed for their intermediate filament proteins, and for neuroendocrine markers. Keratins were present in 6 of 10, vimentin in all 10, and the 68 kilodalton kD neurofilament subunit protein in 6/10 tumors. Keratins numbers 8 and 18 were most prevalent, whereas only traces of keratins 19 and 7 were found. Eight tumors were positive for synaptophysin at least focally, and 3 showed extensive positivity in more than 30% of tumor cells. The tumors showed approximately similar levels of neuron specific enolase (NSE) expression as judged by immunohistochemistry. Chromogranin was not detected, and there was no immunoreactivity for 3 neuropeptides (calcitonin, gastrin, somatostatin). In normal adrenal cortex, neuron-specific enolase, synaptophysin and neurofilaments were restricted to the nerves seen between the cortical cells. Electron microscopy revealed clusters of dense-core granules in 4 of 5 tumors, consistent with neuroendocrine granules. These results indicate that adrenocortical carcinomas may show signs of neuroendocrine differentiation and share some features with the adrenal medullary tumors. PMID- 1735955 TI - Association of the human spasmolytic polypeptide and an estrogen-induced breast cancer protein (pS2) with human pancreatic carcinoma. AB - The human pS2 gene, isolated from the breast carcinoma cell line MCF-7 and shown to be under estrogen transcriptional control in a subclass of breast cancer cells was reported to be secreted in normal stomach surface epithelial cells, whereas additional gastrointestinal tissues like pancreas and colon do not secrete pS2 at all. In porcine pancreas, a spasmolytic polypeptide (sharing domains of homology with pS2) was observed; a corresponding human gene (hSP) was shown to be active in normal stomach mucosa. hSP and pS2 gene activity in normal and neoplastic pancreas tissues was then compared. Whereas both genes are inactive in normal pancreatic cells, activation of the pS2 sequence in a primary pancreatic carcinoma cell culture and in 23 tumor tissues was noted when investigated by immunostaining. In all cases when pS2 showed a regular 0.6 kb transcript, hSP displayed a transcript of 0.7 kb. Six of these tumors showed a reduced pS2 immunoreactivity and, at the same time, aberrant pS2 mRNA bands and a complete shut-down of the hSP gene were noted. In one case, whereas normal pancreas remained negative, the corresponding tumor and its metastasis displayed regular transcripts of pS2 and hSP. This remarkably high correlation suggests that pS2 and hSP expression in the pancreatic tumors, but not in their corresponding healthy tissue is significantly linked to molecular steps leading to tumorigenesis. PMID- 1735956 TI - Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-competent tau and accumulation of abnormal tau-isoforms (A68 proteins). AB - Paired helical filaments, the dominant filamentous components of Alzheimer's disease (AD), neurofibrillary tangles (NFT), neuropil threads, and the dystrophic neurites associated with amyloid rich senile plaques, are composed of abnormally phosphorylated derivatives of tau known as A68 proteins. Indeed the inappropriate phosphorylation of Ser396, which is adjacent to the microtuble binding domain in tau, may contribute to the transformation of tau into A68 and prevent A68 from efficiently binding to microtubules. The reduced levels of normal soluble tau proteins in AD brains may be the consequence of a multi-step process whereby normal tau is converted into A68 and sequestered in paired helical filaments. To elucidate the events involved in this process, we compared the relative levels of binding-competent (BC) and binding-incompetent (BI) tau with the level of A68 in six different regions (hippocampus, fornix, frontal grey and white matter, and cerebellar grey and white matter) of fresh AD and control brains. When the AD brains were compared as a group with neurologically normal and diseased non-AD controls, quantitative immunoblot analysis demonstrated a selective reduction of BC tau in regions of the AD brains with abundant neurofibrillary lesions (NFTs, neuropil threads, and senile plaque neurites) and in their associated white matter areas. The level of BI tau was similar in both AD and control brains. In contrast, A68 was present only in the AD brains, but it was confined to those brain regions with abundant NFTs, neuropil threads, and senile plaques. We view the reductions in BC tau in fornix and frontal white matter to be a consequence of the reductions in their associated grey matter regions i.e., hippocampus and frontal grey matter. Although there is no strict relationship between the reduction of BC tau and the level of A68 within an individual brain, the comparison of the AD group with the control group suggests that the grey matter of the affected regions may be the site for the conversion of BC tau into A68. Further, this process may occur rapidly or via pathways that do not involve BI tau since the levels of BI tau were similar in AD and control brains. Although the complete sequence of events leading to the transformation of tau into A68 and paired helical filaments remains to be elucidated, our data provide compelling evidence that A68 proteins are generated from tau-proteins in selected regions of the AD brain where neurofibrillary lesions comprised of paired helical filaments accumulate. PMID- 1735957 TI - Biological characteristics of primary cultures of human gallbladder epithelial cells. AB - Epithelial cells of the gallbladder have potential to represent an important model for studies of ductal epithelial in normal and pathological states. We therefore initiated studies to establish human gallbladder epithelial cells (GBEC) in culture. GBEC were isolated by trypsinization of small tissue fragments from human gallbladders obtained at cholecystectomy; cells were plated on tissue culture dishes and grown in defined MCDB 153 medium containing added growth factors. In this medium, GBEC showed a plating efficiency of approximately 1%; those GBEC that attached formed colonies and proliferated, as demonstrated by autoradiographic analysis of [3H]thymidine incorporation into DNA. Cultured GBEC expressed two markers found on GBEC in situ, i.e., gamma-glutamyl transpeptidase and cytokeratin 19. By using various attachment substrates, with and without added serum, increased plating efficiency and better growth were achieved. When type IV collagen was used as substrate and 10% fetal bovine serum was added to MCDB 153, passage of GBEC was possible, and cells proliferated through five to six population doublings. GBEC in culture under all conditions eventually enlarged, showed vacuolization, and demonstrated irreversible growth arrest. Nonetheless, the culture conditions described here allow for preparation of large quantities of highly enriched human GBEC. PMID- 1735958 TI - Investigation of nuclear c-MYC oncoprotein expression in human hematopoiesis: suitability of a rapid and reliable semiquantitative evaluation system. AB - The biologic functions mediated by the nuclear protooncogene, c-MYC are correlated to gene dosage. Since automated quantification programs are expensive, time-consuming and not easily available, and since analysis by flow cytometry is difficult in the case of nuclear antigens, we examined the suitability and reproducibility of a semiquantitative in situ evaluation system. This system was based on the percentage of nuclear area staining positively, and comprised the following categories: 0: negative, 1+: single scattered grains of the immunocytochemical staining product, 2+: confluence of grains to patches but less than 50% nuclear area positive, and 3+: greater than 50% positive nuclear area. In addition, sensitivity and specificity of two anti-c-MYC antibodies were investigated. Although both antibodies differed slightly in staining pattern and sensitivity, the four quantification categories were applicable for immunostainings of both antisera and highly reproducible when re-evaluated by the same observer (r = 0.98; p = 0.0001) or a second investigator (rAb155 = 0.98, rAb DCPm = 0.96; p = 0.0001), both reading blindly and independently. Comparing our semiquantitative evaluation categories and results of computer-assisted image analysis, the percentage of positive nuclear area (p less than 0.0001), the median staining intensity (p less than 0.0001), and the product of both (p less than 0.0001) differed significantly in the four evaluation categories. This result still held true after correction for nuclear size, which differed appreciably in various cell types (p less than 0.0001). The product of positive nuclear area, staining intensity and nuclear size (microns 2), which best approximates the absolute amount of c-MYC within a certain cell, was clearly different within the four staining categories (p less than 0.0001) and did not depend on cellular morphology within the staining categories 0 to 2. Also, the immunocytochemical technique proved highly reproducible (median day/day variance 0.65% (0-13); r = 0.995). The practicability of this system for semiquantification was demonstrated by (a) correlation of H score values of immunocytochemical stainings with densitometric scans of Western blots and (b) by the fact that peripheral blood lymphocytes, Phytohemagglutinin stimulated blasts, 13 cases of multiple myeloma and HL-60 cells differed concerning their estimated c-MYC amounts (p = 0.0125). This confirms on the effector molecule level results previously reported from mRNA in situ and Northern blotting analyses. We conclude that a simple and highly reproducible evaluation system can be used for in situ comparison of nuclear oncogene dosage. PMID- 1735959 TI - Use and understanding of adverbial conjuncts: a developmental study of adolescents and young adults. AB - The use and understanding of two types of adverbial conjuncts, concordant (e.g., similarly, moreover, consequently) and discordant (e.g., contrastively, rather, nevertheless), was examined developmentally in 120 adolescents and young adults. Four groups of 30 students participated. Mean ages of the groups were 12:9, 15:10, 19:2, and 23:8 (years:months). The results demonstrated an increasing ability to use and understand these words in the written mode. An interesting discrepancy emerged between the use and the understanding of adverbial conjuncts, a finding that resembled the well-documented discrepancy between the use and the understanding of spoken words in young children. Although young adults had mastered the words in terms of their understanding, they continued to show some difficulty using the words correctly. It was also found that the two types of conjuncts were equally difficult, a result that failed to support Piaget's (1928) hypothesis concerning the greater difficulty of discordant connectives. Factors that may contribute to the development of adverbial conjuncts are discussed. PMID- 1735960 TI - Comprehension problems in children with specific language impairment: literal and inferential meaning. AB - A group of 61 schoolchildren with specific language impairment (SLI) was compared with a control group on a comprehension task, in which the child was questioned about a story that had been presented either orally or as a series of pictures. Half the questions were literal, requiring the child to provide a detail that had been mentioned or shown explicitly in the story. The remainder required the child to make an inference about what had not been directly shown or stated. SLI children were impaired on this task, even after taking into account "comprehension age," as assessed on a multiple-choice test. However, the effects of mode of presentation and question type were similar for control and SLI groups. Children who fitted the clinical picture of semantic-pragmatic disorder had lower scores than other SLI children on this task. In addition, they were more prone to give answers that suggested they had not understood the question. However, as with the other SLI children, there was no indication that they had disproportionate difficulty with inferential questions. It is concluded that SLI children are impaired in constructing an integrated representation from a sequence of propositions, even when such propositions are presented nonverbally. PMID- 1735961 TI - Measurement of communicative intentions in normally developing children during structured and unstructured contexts. AB - The purpose of this study was to examine the effect of sampling context on measurements of communicative intentions expressed by 15 normally developing children during the prelinguistic, one-word, and multiword stages. A communication sample using both structured and unstructured contexts was collected from each subject as he or she interacted with a clinician and parent at each language stage. Direct comparisons were made between the uses of requests and comments during the structured and unstructured sampling contexts. The results indicated that the mean number of requests and comments increased significantly from the prelinguistic to the multiword stage in both contexts. Significantly more requests were used during the structured context, but no significant difference was found between the numbers of comments used in the two contexts. Factors to consider in sampling communication from developmentally young children are discussed. PMID- 1735962 TI - Echolalic responses by a child with autism to four experimental conditions of sociolinguistic input. AB - Studies of the immediate verbal imitations (IVIs) of subjects with echolalia report that features of linguistic or social input alone affect the number of IVIs elicited. This experimental study of a child with echolalia and autism controlled each of these variables while introducing a systematic change in the other. The subject produced more (p less than .05) IVIs in response to unknown lexical words presented with a high degree of directiveness (Condition D) than in response to three other conditions of stimulus presentation (e.g., unknown lexical words, minimally directive style.) Thus, an interaction between the effects of linguistic and social input was demonstrated. IVIs were produced across all conditions, primarily during first presentations of lexical stimuli. Only the IVIs elicited by first presentations of the lexical stimuli during Condition D differed significantly (p less than .05) from the number of IVIs elicited by first presentations of lexical stimuli in other conditions. These findings viewed together suggest that the occurrence of IVIs was related, at least for this child, to an uncertain or informative event and that this response was significantly greater when the lexical stimuli were unknown and presented in a highly directive style. PMID- 1735963 TI - Measurable outcomes of instructions to modify normal parent-child verbal interactions: implications for indirect stuttering therapy. AB - This study was a preliminary analysis of the differential effects of instructions to slow maternal speech rate, or to slow and simplify maternal speech when conversing with normally fluent children. Twenty mothers and their normally fluent children participated. Instructions to slow maternal rate resulted in maternal speech simplification as a by-product. No significant differences were found between the effects of the two sets of instructions. Furthermore, children's speech rate and language complexity did not parallel maternal adjustments. These last findings are problematic for some of the premises that underlie the use of parental counseling as a component of indirect therapy for stuttering. PMID- 1735964 TI - Auditory temporal acuity in normally achieving and learning-disabled college students. AB - Recent research has suggested that deficits in several metalinguistic/phonological abilities, such as short-term verbal memory and phoneme segmentation, may be etiologic factors in specific reading disability, and it has been speculated that these weaknesses may result from a more fundamental deficit in the processing of temporal, auditory stimuli. This study examined the auditory temporal processing skills of reading-disabled, math disabled, and normally achieving college students. The math-disabled group was included to control for the possibility that poor temporal processing is a "marker" variable for learning disability rather than being related specifically to reading disability. Subjects were assessed on a battery of psychophysical tasks that included five tests of temporal processing. The reading-disabled group performed significantly more poorly on the temporal tasks but performed as well as the other groups on the simple pitch and loudness discrimination tasks. In spite of the significant difference on the temporal tasks, the majority of reading-disabled subjects performed within the same range as the subjects in the other two groups, and there were also some normally reading subjects who performed poorly on the temporal processing tasks. These findings suggest that poor temporal processing is neither a necessary nor a sufficient cause of reading disability, but that there is a modest association between the two domains. PMID- 1735965 TI - Auditory distortion products measured with averaged auditory evoked potentials. AB - The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs. The amplitude of the AEP-DPs was evaluated as a function of f2/f1 ratio (1.12-1.52) and primary frequency (500 Hz-2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/f1 ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400-Hz f1 primaries was maximum for the middle f2/f1 ratios (1.22, 1.32, and 1.42). The AEP CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries. PMID- 1735966 TI - Effects of stimulus phase on the normal auditory brainstem response. AB - The purpose of this investigation was to determine the effects of stimulus phase on the latencies and morphology of the auditory brainstem response (ABR) of normal-hearing subjects. Although click stimuli produced equivalent ABR latencies for the rarefaction and condensation phases, the subtraction of the waveforms from the two phases yielded a difference potential. Tone pip stimuli produced polarity differences that were inversely related to stimulus frequency: the higher the frequency, the smaller the ABR latency differences between responses to rarefaction and condensation stimuli, and the smaller the difference potentials. Thus, whereas the latency of click-evoked ABR is dominated by high frequency responses with equivalent latencies regardless of stimulus phase, low frequency responses contribute to the overall morphology of the ABR that yields the phasic difference potential. The implications of these findings are discussed with reference to subjects with high-frequency hearing losses. PMID- 1735967 TI - Comparison of responses to air, water, and closed-loop caloric irrigators. AB - Three types of commercially available caloric irrigation units--air, water, and closed-loop--were evaluated for nystagmus response patterns and comfort. Electronystagmographic recordings were analyzed for slow-phase velocity, response duration, amplitude, frequency, and test-retest reliability. Significant differences were found among the three types of irrigators, between warm and cool irrigators, and between male and female subjects. Test-retest reliability was adequate for all three units. Subjects clearly favored the closed-loop system over the water and air irrigators, but the water irrigator yielded the most robust caloric response. PMID- 1735968 TI - Speech perception in adult subjects with familial dyslexia. AB - Speech perception was investigated in a carefully selected group of adult subjects with familial dyslexia. Perception of three synthetic speech continua was studied: /a/-/e/, in which steady-state spectral cues distinguished the vowel stimuli; /ba/-/da/, in which rapidly changing spectral cues were varied; and /sta/-/sa/, in which a temporal cue, silence duration, was systematically varied. These three continua, which differed with respect to the nature of the acoustic cues discriminating between pairs, were used to assess subjects' abilities to use steady state, dynamic, and temporal cues. Dyslexic and normal readers participated in one identification and two discrimination tasks for each continuum. Results suggest that dyslexic readers required greater silence duration than normal readers to shift their perception from /sa/ to /sta/. In addition, although the dyslexic subjects were able to label and discriminate the synthetic speech continua, they did not necessarily use the acoustic cues in the same manner as normal readers, and their overall performance was generally less accurate. PMID- 1735969 TI - Coupling of FM systems to individuals with unilateral hearing loss. AB - This study examined the attenuation characteristics of five FM system sound delivery options for a group of 10 adults and 15 children (5-13 years). Sound delivery options included a tube-fitting, lightweight headphones, a CROS earmold with tubing, a CROS earmold with a snap-ring, and a standard snap-ring earmold with a vent. Attenuation was defined as the difference between probe-tube microphone measures of the ear canal resonance and the SPL in the ear canal with each sound delivery option in place. A statistically significant but clinically inconsequential difference in attenuation for the CROS earmold with tubing was noted between adults and children. No significant differences in attenuation for any of the other sound delivery options were noted between adults and children. An investigation of the relationship between magnitude of attenuation and percentage of the ear canal occluded suggests that degree of occlusion is a major factor in determining degree of attenuation provided by a particular sound delivery option. Results also indicate that significant attenuation of high frequency signals can occur with earmolds commonly considered nonoccluding. Caution should be used in fitting hearing aids or FM systems to individuals with normal high-frequency hearing sensitivity to prevent attenuation of unamplified high-frequency speech information. PMID- 1735970 TI - Acoustic interpretation of the voice range profile (phonetogram). AB - The voice range profile (VRP) is a display of vocal intensity range versus fundamental frequency (F0). Past measurements have shown that the intensity range is reduced at the extremes of the F0 range, that there is a gradual upward tilt of the high- and low-intensity boundaries with increasing F0, and that a ripple exists at the boundaries. The intensity ripple, which results from tuning of source harmonics to the formants, is more noticeable at the upper boundary than the lower boundary because higher harmonics are not energized as effectively near phonation threshold as at maximum lung pressure. The gradual tilt of the intensity boundaries results from more effective transmission and radiation of acoustic energy at higher fundamental frequencies. This depends on the spectral distribution of the source power, however, At low F0, a smaller spectral slope (more harmonic energy) produces greater intensity. At high F0, on the other hand, a shift of energy toward the fundamental results in greater intensity. This dependence of intensity on spectral distribution of source power seems to explain the reduced intensity range at higher F0. An unrelated problem of reduced intensity range at low F0 stems from the inherent difficulty of keeping F0 from rising when subglottal pressure is increased. PMID- 1735971 TI - The late auditory evoked potential masking-level difference as a function of noise level. AB - The purpose of this study was to determine whether the masking-level difference (MLD) obtained with the late (P2) auditory evoked potentials has characteristics similar to those reported for the behavioral MLD with respect to the effects of noise level. Psychoacoustic studies have shown that the magnitude of the MLD increases as a function of the noise level. In the present study, P2 thresholds were measured in SoNo (signals and noise in phase at the ears) and S pi No (signals out of phase and noise in phase at the ears) conditions for noise levels of 0-60 dB pressure spectrum level (Lps). Subjects were 5 normal-hearing young adults. The difference in SoNo and S pi No thresholds, or the MLD, increased linearly as the noise levels increased through 60 dB Lps, whereas the behavioral MLD magnitude is reported to saturate at high noise levels. These results suggest that the late-potential MLD reflects characteristics similar to, but not identical with, those of the behavioral MLD. PMID- 1735972 TI - Spectral pattern discrimination by children. AB - This research measured the ability of 47 children, aged 4-9 years, to use spectral shape cues to discriminate among random-intensity sounds. The children were tested in forced-choice paradigms that were embedded in a video game format. Two classes of sounds were studied: tonal complexes with sinusoidally rippled amplitude spectra, and synthetic speech sounds (isolated vowels and consonants). The discriminability of the sounds was measured both in quiet and in a background of wide-band noise. Although the intersubject variability in performance was high, especially among the youngest children, the results revealed a substantial age effect. For both classes of sounds, the performance of the younger children was significantly poorer than the performance of an adult control group. However, there was no evidence in the data that the masking effect of the noise was greater for the children than for the adults. PMID- 1735973 TI - Effects of aging on time-gated isolated word-recognition performance. AB - This investigation was designed to study real-time isolated monosyllabic word recognition performance and the feasibility of applying time-gated NU-6 word recognition test materials for real-time assessment of older listeners. Methods and materials developed in a previous investigation were used to obtain time gated performance measures from 37 older listeners (mean age = 69 years). The older listener performance measures were compared with extant data from 20 normally hearing young adult listeners (mean age = 22 years). Specifically, listener confidence and accuracy by gate as well as listener isolation point, confidence at the isolation point, and total acceptance point measures were evaluated. The results show that major events in the real-time understanding process occur at a slower pace among older listeners. The data indicate that the time-gating method has excellent potential for future research among elderly listeners. PMID- 1735974 TI - Comparing tongue positioning by normal-hearing and hearing-impaired children during vowel production. AB - Glossometric measures of tongue positions of 10 normal-hearing (NH) and 10 profoundly hearing-impaired (HI) children were compared during production of the eight vowels /i,I,E,ae,u,U,o,a/. The NH subjects used tongue positions with distinct vertical distances from the hard palate and discrete tongue shapes to distinguish the front vowels and the back vowels. The HI subjects produced vowels using a reduced vertical range and singular flat, high-back tongue shape. Token to-token variability was greater for the HI subjects. Listener identifications of the vowels produced by the HI subjects fell in three categories: highly variable responses to /i/, low vowels for /I,E,ae,a/, and back vowels for /u,U,o/. The centralized, generally undifferentiated tongue positions and listener identifications for the HI subjects coincided with suppositions made from previous perceptual, acoustic, and physiologic findings. PMID- 1735975 TI - Articulation rate in 3- and 5-year-old children. AB - The major purposes of this study were to provide normative data on articulation rate in preschool children and to examine the influence on articulation rate of age, gender, context, and utterance length. The subjects were twenty 3-year-old children and twenty 5-year-old children, equally balanced for gender. Durational measures of utterances were analyzed in syllables and phones per second in both spontaneous and imitated speech contexts. The articulation rate of the 5-year-old subjects was significantly faster than that of the 3-year-olds. Spontaneous speech was significantly faster and more variable than imitated speech. Some gender differences were found. Measures in syllables per second and phones per second, although not always yielding identical results, were found to be highly correlated. PMID- 1735976 TI - Cross-cultural attitudes toward speech disorders. AB - Speech-language pathologists serving multicultural populations may encounter unfamiliar beliefs about speech disorders among the members of different cultures. This study used a questionnaire to look at attitudes toward four disorders (cleft palate, dysfluency, hearing impairment, and misarticulations) among 166 university students representing English-speaking North American culture and several other cultures (e.g., Chinese, Southeast Asian, Hispanic). The results showed significant group differences on items involving the subjects' beliefs about the emotional health of persons with speech disorders and about the potential ability of speech-disordered persons to change their own speech. PMID- 1735977 TI - Vocal tract area function estimation from midsagittal dimensions with CT scans and a vocal tract cast: modeling the transition with two sets of coefficients. AB - The generation of area functions from measurements of the sagittal section is an important step in the study of the relation between vocal tract geometry and speech acoustics. We present a new model to perform this transformation, inspired by the alpha beta model of Heinz & Stevens (1965). Our model is based on analysis of a vocal tract cast for large sagittal dimensions and for small sagittal dimensions on CT scans of the vocal tract constriction zones for the three cardinal vowels [i, a, u] of French. We extracted two sets of coefficients, appropriate for large and small sagittal dimensions respectively. We then compared the predictions of the model with those of other models from the literature. Finally, the usefulness of this dual coefficient procedure for the acoustic simulation of vowels was tested using sagittal sections generated by an acoustic model of the vocal tract. PMID- 1735978 TI - Articulatory function after resection of the tongue and floor of the mouth: palatometric and perceptual evaluation. AB - Linguapalatal contact patterns and the time course of changes in contacts during utterances of/asa, ata, a sa, aca/ were measured using electropalatography (EPG). The relations between these data and perceptual scores in 17 glossectomized patients after various surgical methods were examined. The linguapalatal contact patterns produced during perceptually less distorted sounds varied with the place and manner of articulation. Patterns having very few contacts or a posterior groove produced more distorted /s/ sounds; however, types of EPG patterns producing less distorted /s/ sounds were relatively frequent. Distortion of the and /c/ sounds was less often produced by variation of the EPG patterns, whereas /t/ sounds were most frequently judged to be highly distorted. Patterns that showed complete constriction along the dental arch or constriction on the anterior portion of the hard palate, as well as rapid release for plosion by the tongue tip, produced less distorted /t/ sounds. The results revealed that glossectomized patients often evidenced defective stop sounds. It was concluded that mobility rather than volume of the residual tongue is required to produce less distorted stops. PMID- 1735979 TI - Stuttered and normal speech events in early childhood: the validity of a behavioral data language. AB - A set of 200 utterances from stuttering and normally speaking children aged 2-4 years was obtained. Each utterance contained a disfluency. A group of 5 sophisticated listeners assigned one of Johnson's eight disfluency categories to each of the 200 utterances. These clinicians showed poor agreement in the categories they assigned. Subsequently, the 200 disfluencies were presented to a group of generalist clinician listeners and a group of unsophisticated listeners, who were asked to judge whether each disfluency was "stuttering" or "normal." The disfluencies judged with high agreement to be "stuttering" and the disfluencies judged with high agreement to be "normal" were not categorically distinguished by the disfluency categories assigned previously by the sophisticated listeners. Further, judged presence of various disfluency categories accounted for only a small portion of the variance in numbers of "stuttering" judgments assigned to disfluencies. It is concluded that it is justifiable to question the validity of the data language used by researchers to describe stuttered and normal speech in early childhood. Several implications of this conclusion are discussed. PMID- 1735980 TI - Acoustic integrity of speech production in children with moderate and severe hearing impairment. AB - Ten normally hearing and 10 age-matched subjects with moderate-to-severe hearing impairment were recorded producing a protocol of 18 basic syllables [/pi/,/pa/,/pu/;/bi/,/ba/,/bu/; /ti/,/ta/,/tu/ ;/di/,/da/,/du/; /ki/,/ka/,/ku/; /gi/,/ga/,/gu/] repeated five times. The resulting 90 syllables were digitized and measured for (a) total duration; (b) voice-onset time (VOT) of the initial consonant; (c) fundamental frequency (F0) at midpoint of vowel; and (d) formant frequencies (F1, F2, F3), also measured at midpoint of vowel. Statistical comparisons were conducted on (a) average values for each syllable, and (b) standard deviations. Although there were numerical differences between normally hearing and hearing-impaired groups, few differences were statistically significant. PMID- 1735981 TI - Phonological behavior in toddlers with slow expressive language development. AB - Toddlers with slow expressive language development were compared to normally speaking age-mates on three global measures of phonological behavior: the average level of complexity of their syllable structures, the number of different consonant phonemes produced, and the percentage of consonants correctly produced in intelligible utterances. The groups were found to differ significantly on all three variables. Further analyses were done, breaking the groups down into narrower age ranges. These comparisons also revealed differences between late talking and normal youngsters. Detailed analyses of the range of phonemes and syllable structures produced, as well as the appearance of phoneme classes within syllable structures and positions, revealed that late talkers showed a delayed rather than a deviant pattern of phonological development. The implications of these findings for identifying and monitoring expressive delay in toddlers are discussed. PMID- 1735982 TI - Change and thoracic surgery. PMID- 1735983 TI - University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial. AB - We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation. PMID- 1735984 TI - Future horizons of lung preservation by application of a platelet-activating factor antagonist compared with current clinical standards. Euro-Collins flush perfusion versus donor core cooling. AB - With the introduction of platelet-activating factor antagonists, a direct inhibition of ischemia-induced reperfusion injury can be achieved by prevention of platelet activation, reduction of microvascular leakage, and platelet activating factor-induced bronchoconstriction. At present, two preservation methods are established for clinical lung preservation: (1) donor core cooling by extracorporeal circulation and (2) pulmonary artery flush with Euro-Collins solution and prostacyclin. We compared the quality of organ preservation obtained with these methods to the application of a platelet-activating factor antagonist (WEB 2170; 0.3 mg/kg) for the donor, perfusion solution, and throughout the first 6 hours of reperfusion in combination with prostacyclin (20 ng/kg/min) and Euro Collins solution (60 ml/kg). Eighteen heterotopic heart and orthotopic left lung transplants were performed in three groups of six dogs each after 6 hours of cold ischemia (group I, donor core cooling; group II, Euro-Collins flush and prostacyclin; group III, Euro-Collins flush, prostacyclin, and WEB 2170). Myocardial preservation was achieved with St. Thomas' Hospital solution (20 ml/kg) in all groups. After transplantation, cardiorespiratory function was assessed at an inspired oxygen fraction of 0.4. After transplantation, superior results were observed in group III, as expressed by significantly improved oxygenation, while cardiac output and pulmonary artery pressures were similar in all groups. We concluded that the use of the platelet-activating factor antagonist WEB 2170 resulted in better lung preservation than current clinical standards. PMID- 1735985 TI - Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia. AB - The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity. PMID- 1735986 TI - Long-term preservation of explanted hearts perfused with L-aspartate-enriched cardioplegic solution. Improved function, metabolism, and ultrastructure. AB - The effects of supplementing oxygenated St. Thomas' Hospital cardioplegic solution No. 2 with L-aspartate and/or D-glucose for the long-term preservation of excised rat hearts were determined with isolated working heart preparations. Left ventricular function was assessed at 37 degrees C with a crystalloid perfusate, before cardioplegic arrest and after 20 hours of low-flow perfusion (1.5 ml/min) with continuing arrest at 4 degrees C, and after this period, again at 37 degrees C with a crystalloid perfusate. Four groups (n = 8/group) of hearts were studied with four cardioplegic solutions: St. Thomas' Hospital solution alone, St. Thomas' Hospital solution with aspartate 20 mmol/L, St. Thomas' Hospital solution with glucose 20 mmol/L, and St. Thomas' Hospital solution plus both aspartate and glucose (20 mmol/L each). The addition of glucose to St. Thomas' Hospital solution made no significant difference in the recovery of aortic flow rates (17.7% +/- 8.6% and 21.6% +/- 7.8% of prearrest values), but when aspartate or aspartate and glucose were present, hearts showed significant improvements (89.8% +/- 5.2% and 85.0% +/- 6.2%, respectively). These improvements were associated with a reduction in the decline of myocardial high energy phosphates during reperfusion, a reduction in cellular uptake of Na+ and Ca++, and a reduction in ultrastructural damage. These results indicate that low flow perfusion with St. Thomas' Hospital solution plus aspartate can considerably extend the duration of safe storage of explanted hearts. PMID- 1735987 TI - Benefits of glucose and oxygen in multidose cold cardioplegia. AB - We tested the effects of glucose and oxygen in cardioplegic solutions on myocardial protection in the isolated perfused working rat heart. Recovery from 2 hours' hypothermic (8 degrees C) cardioplegic arrest was examined in 93 hearts. Cardioplegic solution, which was delivered every 15 minutes, was supplemented with glucose 28 mmol/L as a substrate or sucrose 28 mmol/L as a nonmetabolizable osmotic control; it was equilibrated with either 98% oxygen or 98% nitrogen, both with 2% carbon dioxide. Four combinations of hyperkalemic cardioplegic solution were studied: nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen glucose. During hypothermic arrest, oxygenation of cardioplegic solution greatly reduced myocardial lactate production and prevented ischemic contracture as indicated by coronary vascular resistance. Glucose increased lactate production modestly but significantly only when the cardioplegic solution was nitrogenated. Although end-arrest myocardial adenosine triphosphate and creatine phosphate were greatly increased by oxygenation of cardioplegic solution (p less than 0.005), we could not detect improved preservation of these high-energy phosphates by glucose. Averaged over reperfusion, percent recovery of cardiac output for the nitrogen-sucrose, nitrogen-glucose, oxygen-sucrose, and oxygen-glucose solutions was 32.3% +/- 6.1%, 45.9% +/- 4.6%, 44.5% +/- 4.6%, and 62.2% +/- 4.5%, respectively. Oxygenation of the glucose solution or addition of glucose to the oxygenated solution significantly improved recovery of cardiac output. The benefits of glucose and oxygen were additive, so that the oxygen-glucose cardioplegic solution provided the best functional recovery. We conclude that the addition of glucose to the fully oxygenated multidose cold cardioplegic solution improves functional recovery without increasing lactate production during arrest. PMID- 1735988 TI - Applicability of noncardioplegic coronary bypass to high-risk patients. Selection of patients, technique, and clinical experience in 3000 patients. AB - Although some surgeons still prefer noncardioplegic coronary bypass, most surgeons are skeptical of its suitability for high-risk patients. We analyzed the first 3000 patients who had primary coronary bypass without cardioplegia since our program's inception. Patients with reoperations, valve operations, or carotid endarterectomies were excluded. Multivariate predictors of operative death included age, sex, left ventricular dysfunction, preoperative intraaortic balloon pumping, and urgency of operation. Eight hundred seventy-nine patients (29%) were more than 70 years of age; 795 (27%) were female; 290 (9.7%) had an ejection fraction less than 0.30, and another 77 (2.6%) had left ventricular aneurysms; 196 (6.5%) had an acute myocardial infarction, and another 397 (13%) had a myocardial infarction less than 1 week preoperatively; 917 (31%) had rest pain in the hospital (preinfarction angina). Only 790 (26%) had elective operations. The overall operative mortality rate was 1.47% (44/3000): The mortality rate for elective operations was 0.5% (4/790); urgent 1.7% (28/1687); emergency 2.3% (12/523). In patients with an ejection fraction less than 0.30 the mortality rate was 6.2% (18/290); with age more than 70 years, it was 3.9% (34 of 879); with acute myocardial infarction it was 3.1% (6/196); and with left ventricular aneurysmectomy it was 1.3% (1/77). Inotropic support after leaving the operating room was needed in 6.6% (199 patients), and 1% (30 patients) required new intraaortic balloon pumping postoperatively (two of these 30 patients died). These results provide reassurance that noncardioplegic coronary artery bypass grafting provides excellent myocardial protection and operating conditions for primary coronary bypass and is particularly suitable for high-risk patients. PMID- 1735989 TI - Durability of porcine valves at fifteen years in a representative North American patient population. AB - Isolated aortic (n = 857) or mitral (n = 793) valve replacement with a porcine bioprosthesis was performed in 1650 patients between 1971 and 1980. Follow-up (total = 12,012 patient-years) extended to more than 15 years and was 96% complete. Patient age ranged from 16 to 87 years; mean age was 59 +/- 11 years (+/- 1 standard deviation) for the aortic valve replacement cohort and 56 +/- 12 years for the mitral valve replacement cohort. The operative mortality rates were 5% +/- 1% (+/- 70% confidence limits) and 8% +/- 1%, respectively, for the aortic and mitral subgroups. Estimated freedom from structural valve deterioration (+/- 1 standard error of the mean) after 10 and 15 years was significantly higher for the aortic than for the mitral valve replacement subgroup (85% +/- 0.4% and 63% +/- 3% versus 78% +/- 2% and 45% +/- 3%, respectively, p = 0.001). Reoperation free actuarial estimates were also significantly greater for the aortic valve replacement cohort: 83% +/- 2% and 57% +/- 3% versus 78% +/- 2% and 43% +/- 3% for mitral valve replacement at 10 and 15 years, respectively. The mortality rate for reoperative aortic valve replacement was 11% +/- 1%; it was 8% +/- 1% for reoperative mitral valve replacement. Importantly, the estimates of freedom from valve-related death (including sudden, unexplained deaths) were relatively high at 10 and 15 years: 78% +/- 2% and 69% +/- 3% in the aortic cohort and 74% +/- 2% and 63% +/- 3% in the mitral cohort (p = not significant). Excluding sudden, unexplained deaths, these estimates were 81% +/- 3% (aortic) and 73% +/- 4% (mitral) at 15 years. Thromboembolism-free rates were 84% +/- 3% (aortic) and 78% +/- 6% (mitral) at 15 years, and freedom from anticoagulant-related hemorrhage was 96% +/- 1% and 89% +/- 2%, respectively. At the time of current follow-up, 13% of patients having aortic valve replacement and 50% of patients having mitral valve replacement were receiving warfarin sodium. The hazard functions for thromboembolism and prosthetic valve endocarditis were constant and remained less than 1%/pt-yr over the entire follow-up period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1735990 TI - Donor heart valves: electron microscopic and morphometric assessment of cellular injury induced by warm ischemia. AB - Cryopreserved allograft valves are increasingly being used as valvular replacements. Leaflet fibroblast viability has been suggested to influence clinical durability. The warm ischemic time is thought to be a critical determinant of this cell viability. The purpose of this study was to apply quantitative morphometric methods to characterize, by transmission electron microscopy, valvular cellular injury resulting from progressive warm ischemic time. Porcine aortic valves were harvested with a spectrum of warm ischemic times (40 minutes and 2, 6, 12, 24, and 36 hours; five valves per warm ischemic time; n = 30) and processed by standard electron microscopic methods. To ensure randomized tissue selection within each warm ischemic time interval, we randomly selected one thin section from each leaflet. The first ten cells in each thin section were photographed and cellular injury was assessed (cell disruption, dilation of endoplasmic reticulum, cytoplasmic edema, nuclear and mitochondrial changes). Nine hundred micrographs have been analyzed by Cochran-Mantel-Haenszel statistics to determine if a significant association between warm ischemic time and cellular injury exists. Our findings indicate a significant association between reversible cell injury through 24 hours of warm ischemic injury (p less than 0.0001). Furthermore, a significant association between irreversible cell injury and progressive warm ischemia through 36 hours was also found. These findings indicate that the ischemic interval after donor death is associated with progressive leaflet cell injury. Cellular damage begins shortly after donor death and continues incrementally throughout 36 hours. After 2 hours of warm ischemic injury 37% of the cells had morphologic evidence of injury. After 6 hours of warm ischemic injury the number of injured cells increased to 73%. By 36 hours 22% of the cells appeared normal. Irreversible cell injury increases with prolonged ischemia and becomes quantitatively impressive at 24 hours, by which time 26% of cells are so affected. Conversely, some cells are resistant to irreversible injury for a prolonged ischemic interval. PMID- 1735991 TI - Clinical evaluation of the Omniscience cardiac valve prosthesis. Follow-up of up to 6 years. AB - From January 1984 to June 1989, 259 Omniscience valve prostheses were implanted in 225 patients. Of the 225 patients; 143 (63.6%) received mitral, 48 (21.3%) aortic, and 34 (15.1%) double valve replacements. The early mortality rate was 8.9%; 97.6% of the patients were included in this study. These patients represent a cumulative follow-up of 407.9 patient-years, with a mean follow-up of 2.03 +/- 0.1 (standard error) years. The late mortality rate was 4.03% overall, which corresponds to 2.0% +/- 0.7%/pt-yr (SE). The annual rate of valve endocarditis was 1.0% +/- 0.5%/pt-yr (SE). The linearized rate of thromboembolism was 1.2% +/- 0.5%/pt-yr (SE). Anticoagulant-related hemorrhage occurred in 15 patients with an annual rate of 3.7% +/- 0.9%/pt-yr (SE). The linearized rate of valve thrombosis was 0.2% +/- 0.2%/pt-yr (SE). By echocardiography the mean mitral valve opening was 75.9 +/- 3.1 degrees (standard deviation) for 27 patients. During follow-up study, 136 (70.8%) patients were in New York Heart Association class I, 44 (22.9%) were in class II, and 12 (6.3%) were in class III; there were 25 (11.1%) patients in class II, 166 (73.8%) in class III, and 34 (15.1%) in class IV preoperatively. Actuarial freedom from thromboembolism was 94.5% +/- 3.6% (SE); freedom from endocarditis, 97.8% +/- 1.0% (SE); freedom from anticoagulant related hemorrhage, 91.5% +/- 2.0% (SE); freedom from valve thrombosis 99.1% +/- 0.8% (SE); and freedom from hemolysis 98.5% +/- 1.2% (SE). Actuarial survival at 6 years is 94.0% + 2.3% (SE) overall. In conclusion, the overall rate of valve related complications with this valve is low. PMID- 1735992 TI - Heart valve replacement with the Sorin tilting-disc prosthesis. A 10-year experience. AB - From 1978 to 1988, 697 patients with a mean age of 48 +/- 11 years (range 5 to 75 years) received a Sorin tilting-disc prosthesis; 358 had had aortic valve replacement, 247 mitral valve replacement, and 92 mitral and aortic valve replacement. Operative mortality rates were 7.8%, 11.3%, and 10.8%, respectively, in the three groups. Cumulative duration of follow-up is 1650 patient-years for aortic valve replacement (maximum follow-up 11.4 years), 963 patient-years for mitral valve replacement (maximum follow-up 9.9 years) and 328 patient-years for mitral and aortic valve replacement (maximum follow-up 9.4 years). Actuarial survival at 9 years is 72% +/- 4% after mitral valve replacement, 70% +/- 3% after aortic valve replacement, and 50% +/- 12% after mitral and aortic valve replacement, and actuarial freedom from valve-related deaths is 97% +/- 2% after mitral valve replacement, 92% +/- 2% after aortic valve replacement, and 62% +/- 15% after mitral and aortic valve replacement. Thromboembolic events occurred in 21 patients with aortic valve replacement (1.3% +/- 0.2%/pt-yr), in 12 with mitral valve replacement (1.2% +/- 0.3% pt-yr), and in seven with mitral and aortic valve replacement (2.1% +/- 0.8%), with one case of prosthetic thrombosis in each group; actuarial freedom from thromboembolism at 9 years is 92% +/- 3% after mitral valve replacement, 91% +/- 3% after aortic valve replacement, and 74% +/- 16% after mitral and aortic valve replacement. Anticoagulant-related hemorrhage was observed in 15 patients after aortic valve replacement (0.9% +/- 0.2%/pt-yr), in 9 after mitral valve replacement (0.9% +/- 0.3%/pt-yr), and in 6 with mitral and aortic valve replacement (0.9% +/- 0.5%/pt-yr); actuarial freedom from this complication at 9 years is 94% +/- 2% after aortic valve replacement, 91% +/- 4% after mitral valve replacement, and 68% +/- 16% after mitral and aortic valve replacement. Actuarial freedom from reoperation at 9 years is 97% +/ 2% after mitral and aortic valve replacement, 92% +/- 4% after mitral valve replacement, and 89% +/- 3% after aortic valve replacement, with no cases of mechanical fracture. The Sorin valve has shown a satisfactory long-term overall performance, comparable with other mechanical prostheses, and an excellent durability that renders it a reliable heart valve substitute for the mitral and aortic positions. PMID- 1735993 TI - Late results after repair of aortic insufficiency associated with ventricular septal defect. AB - The late results of 70 patients aged 1.96 to 35.9 (mean 10.1) years who had repair of ventricular septal defect and aortic insufficiency from 1968 to 1988 were reviewed. The ventricular septal defect was subcristal in 50 and subpulmonary in 20 patients. Two thirds were situated immediately below some part of the right coronary leaflet with prolapse of that leaflet. Most of the remainder were below the right commissure or the anterior part of the noncoronary leaflet with prolapse of one or both adjacent leaflets. Associated structural defects, usually including some fusion at a commissure, were present in 18 of the 70 patients and occurred more often with a ventricular septal defect in or below the commissure between the right and noncoronary leaflets (p less than 0.001). Follow-up ranged from 1.9 to 19.6 (mean 9.8) years. There were no early deaths or cases of atrioventricular block, but there were two late deaths. Patient survival rate was 96% at 10 years. Freedom from valvuloplasty failure and freedom from reoperation were 76% and 85%, respectively, at 10 years. The major predictor for failure by multivariate analysis was the presence of an associated structural defect (p less than 0.01). Age at repair and position of the ventricular septal defect were not significant risk factors. We conclude that aortic valvuloplasty produces good palliation in most children. The few failures occurred early and chiefly in patients with associated structural valve defects that occurred more frequently in children who had a ventricular septal defect in the right commissure, where both the right and noncoronary leaflets may be affected. PMID- 1735994 TI - Oblique transseptal left atriotomy for optimal mitral exposure. AB - Twenty patients underwent mitral valve replacement or other surgical procedures within the left atrium with Dubost's transseptal left atriotomy. The left atrium was grossly enlarged in six patients. Exposure was considered to be excellent in 13 patients and poor in only two. One patient (with a second aortic and mitral valve replacement) required a permanent pacemaker after operation, none had a residual shunt at the atrial level, and none required reoperation for bleeding. The Dubost transseptal left atriotomy affords excellent exposure of left atrial structures, is easy to close, and does not increase the prevalence of postoperative rhythm disturbances. PMID- 1735995 TI - Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group. AB - Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement. PMID- 1735996 TI - Pulmonary transplantation. Early and late results. The Toronto Lung Transplant Group. AB - Between November 1983 and March 1991, we performed 50 single and 40 double lung transplants in 82 recipients. Early deaths occurred in six (13%) single and in eight (21%) double lung transplant recipients. Late deaths occurred in 11 (28%) single and in one (3%) double lung recipients. Twenty-three of 37 (62%) single and 17 of 24 (71%) double lung transplant recipients have survived at least 1 year after the operation. In patients surviving at least 3 months after the operation (36 of 47 single lung transplant [77%] and 28 of 37 double lung transplant recipients [76%]), significant improvement occurred in arterial blood gases, pulmonary function tests, and exercise capacity. During our initial experience, airway anastomotic complications were the main cause of early morbidity and mortality. With newer surgical techniques and improved perioperative care, airway complications are now uncommon. Infectious complications, either bacterial (Pseudomonas cepacia) or viral (cytomegalovirus), are now the main cause of early mortality. Chronic rejection in the form of obliterative bronchiolitis has become a frequent cause of late morbidity. PMID- 1735997 TI - Heart-lung transplantation in situs inversus. A case report in a patient with Kartagener's syndrome. AB - After a long history of recurrent chronic pulmonary infections in a 25-year-old woman with Kartagener's syndrome, a heart-lung transplantation was performed. A modified surgical procedure was needed to perform transplantation because of the presence of a situs inversus, which is usually associated with bronchiectasis and sinusitis in this congenital syndrome. A large single atrium was created with both the right and left recipient atria used to facilitate anastomosis with the donor's right atrium. The patient was discharged after resolution of early ventilatory complications and is in good condition 8 months after transplantation. PMID- 1735998 TI - Lung transplantation. Analysis of thirty-six consecutive procedures performed over a twelve-month period. The Washington University Lung Transplant Group. AB - A consecutive series of 36 lung transplant procedures in 35 patients, performed over a 12-month period, has been reviewed. There were 14 men and 21 women undergoing 23 single, 12 bilateral, and one en bloc double lung transplant. There were one hospital death and three late deaths in the series, giving a hospital survival rate of 97.2% and a 1-year actuarial survival figure of 91.7%. Airway complications occurred in six patients (17.2%), one of whom died. Cytomegalovirus infection was demonstrated in 18 patients (51%), but no deaths have resulted. The most common cardiac complication was an atrial tachyarrhythmia (nine patients, 25.7%) and three patients had a cardiac arrest, but all were successfully resuscitated. Twelve patients required a further 25 surgical procedures after transplantation; however, renal and hematologic complications were uncommon. The prevalence and management of the other associated complications is discussed. PMID- 1735999 TI - Surgery for effort thrombosis of the subclavian vein. AB - Between February 1988 and March 1991, 28 patients with effort thrombosis of the subclavian vein were treated with a combined approach of thrombolytic therapy followed by surgical therapy. Three categories were seen: group I (six patients), acute stage (less than 5 days); group II (seven patients), subacute stage (6 days to 2 weeks); and group III (15 patients), chronic stage (more than 2 weeks). Group III was divided into two subgroups: subgroup A, seven patients with a short obstructed segment (less than 1/2 inch), and subgroup B, eight patients with a long-obstructed segment (1 to 6 inches). During venography a catheter is placed within the thrombus for continuous infusion of urokinase (3000 U/kg/hr) for 12 to 24 hours. After complete clot lysis, resection of the first rib via a subclavicular approach is undertaken. Vein patch angioplasty was required in two patients in group I, six in group II, and seven in group III, subgroup A. Bypass of long-obstructed vein segments was attempted in only four (group III, subgroup B). Decompression and reestablishment of normal vein caliber was achieved in 100% of groups I and II and in 86% of group III, A. In only one patient of group III, B, a saphenous vein bypass remained open (25%). Operative technique is described. PMID- 1736000 TI - Quantitative analysis of regional wall thickening by transesophageal echocardiography. AB - To develop a method for quantitative analysis of regional left ventricular function from transesophageal two-dimensional echocardiograms, we conducted studies 10 and 20 minutes after induction of anesthesia in 16 patients with normal hearts who were undergoing minor orthopedic operations. Wall thickening was measured with the centerwall method along 100 chords drawn perpendicular to a line constructed around the center of the ventricular wall, midway between the endocardial and epicardial contours. Thickening, either normalized by the length of the end-diastolic perimeter or expressed as a percentage of the end-diastolic wall thickness at each chord, was compared with measurements of endocardial motion. Wall motion was relatively diminished in the anteroseptal region and enhanced on the contralateral wall, but wall thickening was homogeneous throughout the contour. Normalized wall thickening was significantly less variable (standard deviation/mean, 0.47 +/- 0.13) in the normal population than were either percent wall thickening (0.53 +/- 0.012) or wall motion (0.51 +/- 0.09) (p less than 0.005 for both comparisons). There was no significant change in regional or global function between 10 minutes and 20 minutes after the induction of anesthesia. In summary, normalized wall thickening as a parameter of regional left ventricular function is more homogeneous and less variable in subjects with normal hearts than is endocardial motion because wall thickening measurements are not subject to cardiac translocation artifacts. This low variability suggests that normalized wall thickening measured by the centerwall method may prove particularly useful for intraoperative and postoperative monitoring of regional left ventricular function by transesophageal echocardiography in patients undergoing both cardiac and noncardiac surgical procedures. PMID- 1736001 TI - Continuous monitoring of blood oxygen saturation of internal jugular vein as a useful indicator for selective cerebral perfusion during aortic arch replacement. AB - We continuously monitored blood oxygen saturation in the internal jugular vein during selective cerebral perfusion for aortic arch operations and evaluated its efficacy as an indicator of cerebral oxygen metabolism. The selective cerebral perfusion method was applied in 11 patients who underwent operations for aortic arch replacement. Blood oxygen saturation in the internal jugular vein was continuously monitored at the bulbus jugularis with a fiberoptic catheter during the operation. Perfusion flow of 500 ml/min was continued for 134.7 +/- 14.9 minutes under moderate hypothermia at 25 degrees C, and bilateral temporal arterial pressure was 40 to 60 mm Hg. Blood gas data were used to estimate oxygen consumption, oxygen extraction ratio, and lactate uptake in the cerebrum. No patients had postoperative cerebral complications. Cerebral oxygen consumption was 2.93 +/- 0.4 ml/min/100 gm under general anesthesia at 36 degrees C. While selective cerebral perfusion at 25 degrees C decreased consumption to 0.92 +/- 0.39 ml/min/100 gm, it fell to about 30% of its former value. Blood oxygen tension in the internal jugular vein showed no significant correlation with rectal temperature. Selective cerebral perfusion did not significantly affect cerebral lactate uptake. In contrast, blood oxygen saturation in the internal jugular vein was significantly affected by temperature and cerebral flow during selective cerebral perfusion, and blood oxygen saturation in the internal jugular vein correlated closely with cerebral oxygen extraction ratio (r = 0.91). Cerebral oxygen metabolism was thus well maintained, and continuous monitoring of blood oxygen saturation in the internal jugular vein was found to serve as a useful indicator under selective cerebral perfusion during operations for aortic arch replacement. PMID- 1736002 TI - Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man. AB - Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group. PMID- 1736003 TI - Surgical treatment of acute type A dissecting aneurysm, with preservation of the native aortic valve and use of biologic glue. Follow-up to 6 years. AB - We present an analysis of 59 patients operated on between 1983 and 1987 for acute type A dissecting aneurysm with aortic valve insufficiency. The ascending aorta was replaced with a Dacron tube, the layers of the dissection were unified with gelatin-resorcine-formaldehyde glue, and the natural aortic valve was preserved. Follow-up every 6 months was subject to actuarial analysis. The hospital mortality rate was 22%. The survivors were studied for 35.9 +/- 18.6 months (mean +/- standard deviation). Eight patients died (six of cardiovascular causes, one of cancer of the colon, and one of an unknown cause). Seventeen (36.9%) had aortic insufficiency, eight mild and nine moderate to severe. Four patients with severe insufficiency had reoperation with valve replacement. Excluding patients who have died or undergone reoperation, 29 of the remainder (90.6%) are free of symptoms. The follow-up survival rate is 61% +/- 6.93% (standard error) including hospital mortality. It is 55.4% +/- 7% (standard error) excluding reoperation and 44.2% +/- 7.1% (standard error) additionally excluding modest or severe aortic insufficiency. The use of gelatin-resorcine-formal glue allowed preservation of the native aortic valve, obviating the need for anticoagulants, and no embolic or hemorrhagic episodes were registered. PMID- 1736004 TI - Effects of dilation with a balloon catheter on the endothelium of the internal thoracic artery. AB - Controlled dilation of the internal thoracic artery with a balloon catheter has been reported to effectively treat intraoperative arterial spasm. It has been shown in laboratory animals that dilation of the internal thoracic artery at prescribed shear force levels will not cause intimal damage. Using scanning electron and light microscopy, we have examined the effects of calibrated balloon dilation on the endothelium of the human internal thoracic artery. In 10 patients with bilateral internal thoracic artery grafting, the artery was dilated with a Fogarty IMAG balloon catheter (Baxter Healthcare Corporation, Edwards Division, Santa Ana, Calif.) that was withdrawn at tensions of 20 or 30 gm. Arterial segments and nondilated control specimens were prepared for scanning electron microscopy. The intimal surface of each internal thoracic artery was evaluated by assigning a score (from 0 to 3) to 10 examined scanning electron microscopy fields; subsequently the arterial tissue was viewed by light microscopy with paraffin-embedded sections stained for elastic tissue. Arteries were obtained from three additional patients so that the microscopic appearance of the arteries could be observed after rough manipulation or removal of the balloon without shearing. The results of this study are as follows: (1) By scanning electron microscopy, dilated internal thoracic arteries yielded consistently higher scores than the control arteries, reflecting severe, tension-dependent alterations of the endothelium, which included marked desquamation of endothelial cells, with extensive areas of complete denudation and pronounced attachment of platelets to these areas; (2) endothelial injury occurred by inflation alone, without shearing by the inflated balloon; (3) by light microscopy, the internal thoracic arteries showed (a) fenestrations of the internal elastic lamina with occasional transmigration of smooth muscle cells through these gaps and (b) foci of intimal thickening without overt atherosclerotic lesions. We conclude that the endothelium of human internal thoracic arteries is highly vulnerable to balloon dilation, which can severely injure the intimal surface. For this reason we prefer not to include this procedure in our protocol for preparing the internal thoracic artery. PMID- 1736005 TI - Penetrating thoracic wounds caused by plastic bullets. AB - Thoracic penetrating injuries caused by a new plastic bullet were studied to determine the nature of the wounds and the appropriate management. Twenty-six casualties from the Israeli-Palestinian conflict (Intifada) were included. The organs most commonly involved were lung (n = 21), bony chest wall (n = 9), heart (n = 3), and diaphragm. Bleeding was at least moderate in 20 patients, amounting in all patients to an average of 975 ml. Thoracotomy was required in 11 patients (42%) mainly because of cardiac injury (n = 3) and aortic or other arterial bleeding (n = 3). Simple oversewing of severed organs (n = 8) or ligation of bleeding vessels (n = 3) was satisfactory. Two patients died (7.7% mortality); one after major liver resection; the other was dead on arrival. We conclude that plastic bullets have a linear course unless displaced by the bony chest wall, when they tend to fragment and cause simple fractures. Fired from a presumed range of at least 70 m, plastic bullets behave like low-velocity missiles, and tissue destruction is minimal. Management should be similar to that of civilian thoracic penetrating trauma. PMID- 1736006 TI - Surgery for Wolff-Parkinson-White syndrome in the very young. PMID- 1736007 TI - Benign bronchoesophageal fistula: reopening four months after double stapling without division. PMID- 1736008 TI - A dilatable prosthesis for banding the pulmonary artery: initial clinical experience. PMID- 1736009 TI - c-abl function in normal and chronic myelogenous leukemia hematopoiesis: in vitro studies with antisense oligomers. AB - By using antisense oligomers the functional role of the c-abl proto-oncogene in the in vitro growth of bone marrow hematopoietic progenitors from normal subjects and patients with chronic myelogenous leukemia (CML) has been evaluated. Light density bone marrow cells (LDBMs) were depleted of adherent cells, pre-incubated for 15 h with the appropriate oligomer at a concentration of 14 microns, and then plated in methylcellulose for the evaluation of colony formation. Both anti-exon Ia and anti-exon Ib antisense oligomers produced a significant inhibition of normal day 14 CFU-GM growth in vitro (n = 5, 41 +/- 11%, and 36 +/- 7%, respectively; p less than 0.01). In contrast, normal BFU-E growth was not significantly influenced by antisense oligomers (n = 5, 14 +/- 21% and 7 +/- 19%, respectively; p less than 0.05). These findings were confirmed by plating CD34 positive progenitors. When interleukin 3 (IL-3) (100 ng/ml) was added to the culture medium during the preincubation of LDBMCs, the inhibitory effects of antisense oligomers on normal CFU-GM growth were abolished. Seven patients with CML were also studied, all of whom had cytogenetic evidence of 100% clonal hematopoiesis. In five patients in the chronic phase, antisense oligomers were inhibitory on in vitro growth of both day 14 CFU-GM (37 +/- 20% and 37 +/- 15%, p less than 0.05) and BFU-E (45 +/- 15% and 41 +/- 11%, p less than 0.05), and this inhibition was not removed by pre-incubation with IL-3. No significant effect was observed on cluster or colony formation in two patients with CML in accelerated or blastic phase, and on in vitro growth of clonogenic cells from the Ph1 positive K-562 cell line. These findings (i) confirm previous observations showing a lineage specific requirement of c-abl function in normal hematopoiesis, and (ii) suggest that the residual c-abl expression has a role in chronic phase CML hematopoiesis, as its inhibition impairs both myeloid and erythroid colony formation in vitro. PMID- 1736010 TI - Transformation of murine pre-B-lymphocytes by v-erb-B: progression to growth factor independence and tumorigenicity. AB - v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia. PMID- 1736011 TI - Detection of residual disease in translocation (14;18) positive non-Hodgkin's lymphoma, using the polymerase chain reaction: a comparison with conventional staging methods. AB - This paper reports the detection of residual lymphoma cells in blood and bone marrow samples from patients with translocation (t) (14;18) positive non Hodgkin's lymphoma by the polymerase chain reaction (PCR) compared with conventional staging techniques. In 15 of 22 samples, in which no lymphoma cells could be detected by morphological examination, t(14;18) positive cells were detected by PCR. In 13 of 21 samples, in which a monoclonal B-cell population was not detectable by immunological marker analysis, PCR was positive. The clinical status (physical examination, imaging techniques, leucocyte count, and occasionally morphology and immunological marker analysis) was documented in 30 patients at the time of PCR analysis. In three of 19 patients with clinical evidence of disease, circulating t(14;18) positive cells were not detectable by PCR. Five of 11 patients in clinical remission from 7 to 47 months, showed t(14;18) positive cells in the blood. Our data show that PCR analysis in t(14;18) positive non-Hodgkin's lymphoma offers a powerful tool in the study of residual disease. PMID- 1736012 TI - Mutations of the p53 gene in B-cell lymphoblastic acute leukemia: a report on 60 cases. AB - Exons 5 to 8 of the p53 gene were examined for mutations in 60 patients with B cell acute lymphoblastic leukemia (ALL), including 50 cases of precursor-B-cell ALL, nine cases of Burkitt (L3) ALL and one case of atypical ALL with surface immunoglobulins and t(8:14) translocation but L2 morphology. Karyotype was available in all patients. DNA was analyzed by polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Three patients showed point mutations in exons 7 or 8, including two of the nine patients with Burkitt ALL and one of the 50 patients with precursor-B-cell ALL. These findings suggest that p53 gene mutations are rare in precursor-B-cell ALL but may be more frequent in Burkitt ALL. In the three patients with p53 mutations, however, the relevance of those mutations to the development or progression of leukemia remained uncertain. PMID- 1736013 TI - Prognostic value of S-phase white blood cell count in B-cell chronic lymphocytic leukemia. AB - Eighty previously untreated patients with B-cell chronic lymphocytic leukemia (B CLL) were analyzed to study the proliferation rate of their peripheral blood (PB) leukocytes to determine its relationship with the extension of the disease and its value in discriminating among patients with similar tumor cell mass. The 80 B CLL patients were distributed into two different groups according to the absolute count of PB S-phase leukocytes: a low proliferative group (less than 1 x 10(9)/I) of 48 patients and a high proliferative group (greater than or equal to 1 x 10(9)/I) of 32 patients. The high proliferative group displayed a higher incidence of splenomegaly (p less than 0.005), hepatomegaly (p less than 0.08), anemia (p less than 0.02) and thrombocytopenia (p less than 0.03) as well as a higher lymphocytic infiltration both in PB (p less than 0.0004) and in bone marrow (BM) (p less than 0.003). These patients also showed a higher incidence of a diffuse pattern of BM involvement (p less than 0.04), advanced clinical stages [stage III/IV (p less than 0.03) and group C (p less than 0.04)] and infections (p less than 0.0008) together with significantly lower IgG (p less than 0.03) and IgM (p less than 0.03) serum levels. Regarding the immunophenotype, there was a greater percentage of either CD19+ (p less than 0.06) and CD19+ CD5+ (p less than 0.05) B-cells, together with a greater reactivity for both the CD25 (p less than 0.04) and CD9 (p less than 0.08) antigens in the high proliferative group. According to the prognostic value of the PB S-phase leukocyte count it was seen that patients with low S-phase white blood cell (WBC) numbers displayed a significantly higher survival (p less than 0.03). In addition, multivariate analysis revealed that the S-phase WBC count, although partially related to other clinical and biological prognostic factors, displayed an important independent value in predicting early deaths in patients with B-CLL. PMID- 1736014 TI - Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. AB - In an attempt to identify prognostic factors for survival and leukemic transformation, 235 untreated patients with primary myelodysplastic syndromes (MDS) were analyzed in a single center retrospective study. To the well known FAB classification of MDS a supplementary group of patients with pure sideroblastic anemia (PSA) was added, characterized by the absence of dysplastic features of non-erythroid cells. Accordingly, the morphological subtypes were refractory anemia (RA), n = 55; PSA, n = 40; RA with ring sideroblasts (RARS), n = 33; RA with excess of blasts (RAEB), n = 53; RAEB in transformation (RAEB/T) n = 29; and chronic myelomonocytic leukemia (CMML), n = 25. Having screened 28 clinical, cytological, and laboratory parameters by univariate analysis, multiple regression analysis identified six variables with independent prognostic value: percentage of bone marrow blasts, serum LDH activity, PSA, hemoglobin concentration, age, and platelet count. If patients with PSA were excluded, the FAB classification no longer contributed independent prognostic information. Based on the results of this multivariate analysis, a simple scoring system was devised for predicting the survival of patients with MDS. A score of unity was allocated to each of the following parameters: bone marrow blasts greater than or equal to 5%, LDH greater than 200 U/I, hemoglobin less than or equal to 9 g/dl, and platelets less than or equal to 100 x 10(9)/I. As a function of their total score, patients were divided into three risk groups (group A, score 0; group B, score 1-2; group C, score 3-4), which differed significantly in both survival and rates of leukemic transformation. The cumulative survival 2 years after diagnosis was 91% in group A, 52% in group B, and 9% in group C (p less than 0.00005). The actuarial risk of transformation to acute myeloid leukemia at 2 years was 0, 19, and 54%, respectively (p less than 0.05). The inclusion of LDH enzyme levels qualified this scoring system for an accurate assessment of patients with CMML whose prognosis is viewed too favorably when rated by other scores. Furthermore, this score was able to identify those patients with RA and RARS who, without showing an excess of marrow blasts, have an unfavorable prognosis. PMID- 1736015 TI - Interstitial deletion of the long arm of chromosome 9 as the sole anomaly in acute myeloid leukaemia is associated with dyserythropoiesis. PMID- 1736016 TI - HTLV-1 associated myelopathy/tropical spastic paraparesis with adult T-cell leukemia. PMID- 1736017 TI - Nursing home case-mix classification and residents suffering from cognitive impairment: RUG-II and cognition in the Texas case-mix data base. AB - Case-mix reimbursement systems for nursing home care are now in use or under consideration in over 20 states. Though many in the long-term care field still debate the relative merits of the various systems, those systems based on the Resource Utilization Groups-II (RUG-II) system used in New York seem to be increasingly popular. However, one of the more serious questions raised concerning RUG-like systems is whether they fully acknowledge the role played by cognitive deficits in determining nursing home residents' care needs. The results of this research indicate: 1) that resource provision and cognitive status are correlated, 2) that residents with higher levels of cognitive impairment appear most frequently in RUG-II categories that have higher case-mix weights, 3) that simply adding some measure of cognitive function does not significantly increase the power of these models, and 4) that the RUG-II model predicts the level of care resources provided to the cognitively intact much better than it predicts those provided to residents suffering from relatively severe disorientation. These results imply that such classification systems may create disincentives for the admission of the most cognitively impaired residents and that the care of these individuals, more than others, may be dependent on facility-to-facility variation. PMID- 1736018 TI - Variations in the use of cesarean delivery for dystocia: lessons about the source of care. AB - Aggregate data show variations in the use of cesarean delivery according to the source of care, which suggests that rising cesarean rates are at least in part attributable to nonmedical factors. In the research presented here, the likelihood of cesarean delivery is examined for low-risk, primiparous women with physicians who practice in a single hospital but are from three practice organizations--a health maintenance organization (HMO), private practice, and a hospital clinic--while controlling for a wide spectrum of clinical factors. Maternal age was found to be a dominant factor in determining the decision for a cesarean delivery, independent of clinical risk and physicians' practice organization. Only among women in their optimal childbearing years (25 to 29 years) was having an HMO physician associated with a lower likelihood of cesarean delivery. The authors conclude that lowering the primary cesarean rate in the 1990's may require more reeducation and clinical policy formulation, with particular attention being paid to maternal age, and less reorganization of services than the aggregate data suggests. PMID- 1736019 TI - Contractual arrangements between HMOs and primary care physicians: three-tiered HMOs and risk pools. AB - Concern about certain contractual arrangements between health maintenance organizations (HMOs) and primary care physicians has led policymakers to consider curbing these arrangements; one law has already been passed. However, these arrangements are complex and their impact is neither obvious nor well understood. This article first presents a conceptual approach to understanding the relationship between HMOs and primary care physicians and discusses how they influence the locus of financial risk and managerial control. It then refines understanding of two critical dimensions (three-tiered HMOs and risk pools) by examining survey responses of 260 HMOs (representing over 50% of total HMO enrollment.) Results of the evaluation led to the conclusion that primary care physicians in three-tiered HMOs are sheltered from some of the financial incentives and contractual arrangements enacted by the HMO and that the reason for using risk pools may be due more to peer group effects or interaction with other incentives, rather than the direct financial implications of the risk pool on individual physicians. These concepts and observations have relevance for other types of health care systems in this country and elsewhere. Policymakers risk enacting misguided policies unless they understand the details of these arrangements. PMID- 1736020 TI - Paid work and unpaid help by caregivers of the disabled and frail elders. AB - Informal caregiving by women, and to a lesser extent by men, is a major source of assistance for the chronically disabled and most dependent older persons living in the community. However, because women's commitment to career employment may diminish, this source of help at the time when (according to demographic trends) the number of very old Americans will increase, the effect of employment on the time they devote to informal caregiving is an important social and economic issue. This study examines two related research questions: 1) how the time allocated to paid work affects the time devoted to unpaid caregiving and 2) how caregiving responsibilities affect work outside the home. The results differ for full-time and part-time work. Estimating a simultaneous equation model, it was found that 1) full-time employment by caregivers reduces the time they allocate to providing unpaid help by 20 hours a week and 2) female caregivers were much less likely than their male counterparts to have full-time jobs. Results also indicate that 1) part-time employment by caregivers has no statistically significant effect on caregiving and 2) caregiving has no effect on women's part time employment. PMID- 1736021 TI - Verbal consultation regarding prescription drugs: findings from a statewide study. AB - In 1984 the Wisconsin Division of Health showed interest in patients' receipt of verbal consultation for prescription drugs and included relevant questions in the Wisconsin Health Status survey to: 1) investigate the receipt of verbal consultation for new and refill prescriptions, 2) allow a comparison of state results with those of a national study that used similar sampling and data collection procedures, and 3) more closely examine the relationships between receipt of verbal consultation and such variables as prescription status (new or refill), age, sex, race, and education. Data were collected from 2,135 randomly selected respondents using Computer Assisted Telephone Interviewing with random digit dialing. After controlling for elapsed time since last prescription, log linear analyses showed the importance of prescription status (new and refill) and respondent's age as correlates of consultation by pharmacy personnel, while prescription status, age, and sex were significant for prescribers. For both prescribers and pharmacy personnel, the authors found no association between client education and receipt of verbal consultation. The absence of verbal consultation cannot be entirely accounted for by client characteristics or prescription status. Based upon their experience, the authors encourage continued monitoring of prescribers' and pharmacists' provision of verbal consultation through questions contained in state and national health status surveys. PMID- 1736022 TI - Profits, community role, and hospital closure: an urban and rural analysis. AB - The number of hospital closures increased substantially after the implementation of Medicare's Prospective Payment System (PPS). This acceleration in closures raised a number of concerns over current payment policies and their impact on access. This paper investigates hospital closures that occurred in 1985 through 1988. A hospital's financial status and mission or community standing were found to be determinants of hospital closure. Closed hospitals are much less likely to be publicly owned but more likely to offer fewer facilities and services, and have fewer cases. This may suggest that the patients directly affected by the closure can be absorbed by other hospitals or other nonhospital providers. Profitability is associated with the Medicare case-mix index and the share of Medicare patients. The findings also suggest that the case mix index may be rewarding some small hospitals in excess of the costs attributable to case-mix. For both urban and rural hospitals, a low share of Medicare patients increased the risk of hospital closure, independently of the relationship between Medicare share and profit. The share of Medicare patients also affected closure indirectly, through its effects on profit. Competition appears to affect the odds of closure through its effects on the number of cases. In addition, hospitals in areas with small or declining population are more at risk than other hospitals in both urban and rural areas. PMID- 1736023 TI - Measuring physician mental workload: reliability and validity assessment of a brief instrument. AB - This study examined the reliability and validity of a brief six-item instrument to measure the mental workload experienced by residents for specific patient visits to an ambulatory care clinic. Participating in the study were twenty-two residents in postgraduate years 1 through 3 who were working in the general outpatient clinic of an inner city, private, nonprofit community hospital. Cronbach's alpha coefficient for the instrument was 0.80. Findings supported several theory-based hypotheses on determinants and performance consequences of mental workload. Mental workload was positively correlated with fatigue (r = 0.42, P = 0.03) and inversely correlated with residents' self-rated experience with patients' problems (r = -0.65, P less than 0.001). Residents' performance was measured through self-ratings and faculty physicians' ratings. Mental workload was inversely correlated with self-rated performance (r = -0.67, P less than 0.001). The correlation of mental workload with faculty physician ratings that reflected the technical dimension of patient care (physician examination, medications, and procedures) was r = -0.38 (P = 0.04). With mental workload squared, the correlation was r = -0.45 (P = 0.02) and the form of the relationship, consistent with the hypothesis, was a slightly downward sloping curve. Limitations of this research are discussed as well as suggestions for further research. PMID- 1736024 TI - Inhibition of [3H]dopamine and [3H]serotonin uptake by cocaine: comparison between chopped tissue slices and synaptosomes. AB - Cocaine inhibits both [3H]dopamine and [3H]serotonin uptake in rat striatum and nucleus accumbens. In a chopped tissue slice preparation, the inhibition curve for [3H]dopamine uptake is biphasic, suggesting two components of uptake, whereas the curve for [3H]serotonin uptake is steep and apparently monophasic. In synaptosomal preparations, both curves are monophasic. Monensin, a sodium ionophore, inhibits uptake but does not change the shape of the cocaine inhibition curve in synaptosomes, suggesting that the biphasic inhibition curves in slices are not likely due to differential sodium gradients across the slices. In tissue slices, only the component which is more sensitive to inhibition by cocaine and related drugs is inhibitable by nicotine. This suggests that the two components of dopamine uptake in tissue slices may be differentially regulated. PMID- 1736025 TI - Effect of mazindol administration on (3H)-N-methylscopolamine binding to rat cerebral cortex. AB - Mazindol has been shown to produce anorexia in several animal species including humans, and its pharmacological effects may be elicited by blockade of neuronal reuptake of dopamine and norepinephrine. Chronic treatment of rats with mazindol (10 mg/kg daily, p.o.) caused an increase in muscarinic receptor density (Bmax = 874.7 femtomoles/mg protein) as compared to controls (Bmax = 629.1 femtomoles/mg protein) in the cerebral motor cortex. An increase in dissociation constant (Kd) values was also observed which changes from 0.57 nM (control) to 1.17 nM after mazindol treatment. The mechanism underlying the observed effect of mazindol on receptors could be related to processes involving other neurotransmitters which also regulate cholinergic activity in the CNS. However, the implications of the eventual dopaminergic control on muscarinic receptors in the cortex is still an open question. PMID- 1736026 TI - Evidence nitric oxide mediates the vasodepressor response to hypoxia in sino denervated rats. AB - Systemic hypoxia, produced in deeply anesthetized, paralyzed rats in which arterial chemoreceptors were denervated, elicited a decrease in arterial pressure (AP) averaging -47 mmHg. Systemic administration of NG-nitro-L-arginine (L NO2Arg), an inhibitor of nitric oxide (NO) synthase, attenuated the hypoxic depressor response by 79% and elevated AP by 21 mmHg. The effects of L-NO2Arg on the hypoxic depressor response and arterial pressure were reversed by systemic administration of L- but not D-arginine. Elevation of AP with arginine vasopressin or reduction of AP with nitroprusside to the pre-L-NO2Arg levels did not modify the fall of AP to hypoxia. Endogenous NO synthesized in vivo from L arginine, mediates most of the hypoxic depressor response. PMID- 1736027 TI - Long-term facilitation of social recognition in rats by vasopressin related peptides: a structure-activity study. AB - The effect of several vasopressin-related peptides was investigated in the social recognition paradigm, that consists of two successive encounters of a resident and a juvenile rat. The decrease of social investigation time of the resident rat during the second encounter served as a measure for social recognition. Single administration (3.0 micrograms, s.c.) of the vasopressin (AVP)-related peptides AVP-(1-8), AVP-(1-7) or AVP-(1-6), injected just after the first encounter, resulted in social recognition after 24 hours. Such an effect was not observed after placebo treatment or an injection with AVP-(1-5), [pGlu4, Cyt6]AVP-(4-8), [pGlu4, Cyt6]-AVP-(4-9), AVP-(7-9) or oxytocin-(1-6)-NH2. The peptide AVP-(1-6) was also active when administered in a dose of 0.3 micrograms in contrast to other peptides. Thus, vasopressin related peptides induce long term facilitation of social recognition and this action resides in the covalent ring structure of vasopressin. This effect resembles the vasopressin-induced facilitation of particular memory processes, as revealed with other behavioral paradigms. PMID- 1736028 TI - Persistent depletion of striatal dopamine and cortical norepinephrine in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydro-3-pyridinol (MPTP-3-OL), an analog of MPTP. AB - MPTP-3-ol injected s.c. once daily for 4 days resulted in a dose-dependent depletion of striatal dopamine and cortical norepinephrine one week after the last dose. MPTP-3-ol was approximately one-fourth as potent as MPTP (1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine) in causing these effects. MPTP-3-ol was oxidized by monoamine oxidase in mouse brain in vitro and resulted in MPP+ (1 methyl-4-phenylpyridinium) formation in brain in vivo, both at about one-fourth the rates with MPTP. The in vitro metabolism of MPTP-3-ol was inhibited by deprenyl, a selective inhibitor of monoamine oxidase type B, and deprenyl pretreatment also blocked the depletion of striatal dopamine and cortical norepinephrine in vivo. Pretreatment with EXP 561, an inhibitor of catecholamine uptake, also prevented the dopamine- and norepinephrine-depleting effects of MPTP 3-ol. Thus, substitution of a hydroxy group on the 3-position of MPTP retains its neurotoxic potential toward catecholamine neurons but reduces potency by decreasing the rate of oxidation via monoamine oxidase type B. PMID- 1736029 TI - Nicotine-induced sensitization to ambulatory stimulant effect produced by daily administration into the ventral tegmental area and the nucleus accumbens in rats. AB - Bilateral injections of nicotine (30 micrograms/side) into the ventral tegmental area (VTA) and the nucleus accumbens (NACC) increased the ambulatory activity in rats. Moreover, daily injections of nicotine (10, 20 and 30 micrograms/side) into the VTA and the NACC for 6 successive days produced sensitization to the ambulatory stimulant effect of nicotine. Sensitization produced by daily injections of nicotine (20 micrograms/side) into both the sites was maintained for withdrawal periods of 10 days. Mecamylamine (2 mg/kg, i.p.), SCH23390 (0.05 mg/kg, i.p.) and spiperone (0.1 mg/kg, i.p.) antagonized nicotine-induced sensitization to the ambulatory stimulant nicotine-induced sensitization to the ambulatory stimulant effect produced by daily injections into the VTA. These results suggest that nicotine-induced sensitization to the ambulatory stimulant effect involves the stimulation of the mesolimbic dopaminergic pathway through the nicotinic acetylcholine receptor (nAChR) in the VTA and the NACC. PMID- 1736030 TI - mCPP but not TFMPP is an antagonist at cardiac 5HT3 receptors. AB - The prototypic arylpiperazines, meta-chlorophenylpiperazine (mCPP), meta trifluoromethylphenylpiperazine (TFMPP) and quipazine are widely studied serotonergic ligands with nonselective effects at 5HT1 and 5HT2 receptor subtypes. The present study was designed to compare the affinities of these arylipiperazines at 5HT3 receptors, and to determine agonist or antagonist activity at 5HT3 receptors. Quipazine showed high affinity at brain 5HT3 receptors (IC50 = 4.4 nM) and was a potent agonist of the von Bezold-Jarisch reflex in anesthetized rats, a response mediated by cardiac 5HT3 receptors. In concentrations that activated 5HT3 receptors, quipazine also antagonized serotonin-induced bradycardia in anesthetized rats. Taken together, these data suggest that quipazine is an agonist/antagonist with high affinity at 5HT3 receptors in both brain and cardiac tissue. Although mCPP also showed relatively high affinity at brain 5HT3 receptors (IC50 = 61.4 nM), it did not activate the von Bezold-Jarisch reflex; instead, mCPP potently antagonized serotonin-induced bradycardia. Thus, mCPP acts as an antagonist at 5HT3 receptors in the periphery. Although both quipazine and mCPP possessed relatively high affinity at brain 5HT3 receptors, TFMPP did not bind appreciably to 5HT3 receptors in brain (IC50 = 2373 nM) and neither activated nor inhibited cardiac 5HT3 receptors. That TFMPP did not interact with 5HT3 receptors, whereas quipazine and mCPP did, is in marked contrast to the similar effects of all three arylpiperazines at other serotonin receptors. The selectivity of TFMPP for 5HT1 and 5HT2 receptors (i.e., its minimal affinity for 5HT3 receptors) suggests that this arylpiperazine may be a preferred ligand relative to mCPP when studying 5HT1 or 5HT2 receptor mediated responses. PMID- 1736031 TI - Is hepatic glycogen content a regulator of glucagon secretion? AB - The role of plasma glucose as a major regulator of glucagon secretion is well established. However, this feedback regulation appears to break down in several states in which a closer relationship is apparently evident between plasma glucagon and hepatic glycogen content. Therefore, we assessed plasma glucagon as well as glucose response (delta glucose) to intravenous (IV) bolus administration of 1 mg glucagon after an overnight fast (a reliable and accurate estimate of the magnitude of hepatic glycogen content) in a population of normal subjects and subjects with hepatic cirrhosis and hyperthyroidism, both of which are disorders characterized by hepatic glycogen depletion. Plasma glucose concentrations were not significantly different in either group. However, plasma glucagon and insulin concentrations were significantly increased and delta glucose significantly decreased in both cirrhotic patients and hyperthyroid patients as compared with normal subjects. Furthermore, a significant relationship (r = -.55, P less than .0001) was noted between delta glucose and plasma glucagon, but not plasma insulin. Therefore, we believe that pancreatic alpha-cell function may be dependent on hepatic glycogen content. Moreover, the primary action of glucagon may be to induce gluconeogenesis in the absence of hepatic glycogen stores due to declining insulin concentrations or insulin resistance. PMID- 1736032 TI - Uptake and hydrolysis of glycylglutamine at the blood-brain barrier. AB - Using an organ balance technique in dogs, we recently found that liver, skeletal muscle, kidney, and intestine participate in clearance of glycylglutamine from plasma. The purpose of the present study was to investigate whether brain does the same. The study of arteriovenous differences of glycylglutamine across brain, during continuous infusion of this dipeptide (12 mumol.min-1.kg-1) in dogs, showed an arteriovenous difference that was never significantly different from zero. To establish a basis for this lack of clearance, we investigated uptake and hydrolysis of glycylglutamine at the blood-brain barrier. The study of brain uptake index of glycylglutamine in rats showed that it was not significantly different from that of sucrose, an impermeable marker (3.2 +/- 0.4 v 3.5 +/- 0.4, n = 4 to 5). When isolated brain capillaries were incubated with glycylglutamine, uptake was only modestly above background activity and appeared to be due to nonspecific binding. Finally, the plasma membrane of brain capillaries lacked hydrolase activity against glycylglutamine. In conclusion, brain appears to be unique among organs in lacking any mechanism for clearance of glycylglutamine from plasma. PMID- 1736033 TI - Short-term energy balance in patients with infections: carbohydrate-based versus fat-based diets. AB - The effects of a carbohydrate-based diet (50% carbohydrate calories, 30% fat calories, 20% protein calories) versus a fat-based diet (28% carbohydrate calories, 55% fat calories, 17% protein calories) on oxidation rates of carbohydrate, fat, and protein were assessed in 12 patients with infections by indirect calorimetry and estimation of urea nitrogen production rate. The diets were given continuously for 18 hours in a randomized cross-over study on 2 consecutive days. Energy supply (kcal/d) was adjusted individually to meet the energy expenditure measured on the preceding day after an overnight fast and was 1,647 +/- 129 (SEM) for the carbohydrate-based diet and 1,655 +/- 131 for the fat based diet. Oxidation rates (kcal/d) for carbohydrate (carbohydrate-based diet, 525 +/- 70; fat-based diet, 363 +/- 84) were different between the diets (P less than .05), whereas no difference could be found for fat (carbohydrate-based diet, 820 +/- 117; fat-based diet, 968 +/- 136) and protein (carbohydrate-based diet, 252 +/- 29; fat-based diet, 236 +/- 23). However, during carbohydrate-based feeding, carbohydrate balance (288 +/- 93 kcal/d) and fat balance (-327 +/- 107 kcal/d) were significantly different from zero (P less than .05), indicating continuous oxidation of endogenous fat and storage of administered glucose. During the fat-based diet, carbohydrate and fat balances were not different from zero. A correlation between energy and substrate balances was not seen during either diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736034 TI - Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity. AB - Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736035 TI - The exogenous origin of trimethylamine in the mouse. AB - Although it is now generally regarded that the origin of urinary trimethylamine (TMA) is via the action of intestinal microflora on precursors such as choline, little direct evidence exists. The normal production of urinary TMA was shown to be absent in germ-free mice and greatly reduced in antibiotic-pretreated animals. Cohabitation of germ-free mice with conventional animals restored their ability to excrete TMA. This study invokes a fundamental role for the intestinal microflora in the provision of TMA from precursors within the food. PMID- 1736036 TI - The influence of meal composition on plasma serotonin and norepinephrine concentrations. AB - Reports concerning changes in plasma neurotransmitter values that result from dietary manipulations have not been published so far. The influence of various meal compositions on platelet-poor plasma (PPP) serotonin (5-HT) and norepinephrine (NE) levels was investigated. Healthy volunteers were subjected to three test meals: a carbohydrate-rich meal (86% carbohydrates), a protein-rich meal (70% protein), and a fat-rich meal (92% fat). After a carbohydrate-rich meal, PPP 5-HT values increased significantly (4.47-fold, P less than .02), whereas a smaller increase (1.66-fold, P = NS) was observed after a fat-rich meal. These effects on PPP 5-HT values could be correlated with insulin plasma levels. A protein-rich meal significantly reduced (P = 0.0011) PPP 5-HT to 28% of initial values, despite an increase in plasma insulin levels. This study has shown that (1) changes in meal compositions influence PPP 5-HT and, to a lesser extent, NE values; (2) the resulting changes in PPP 5-HT levels parallel those reported for brain neurotransmitters; and (3) these results seem to indicate that PPP 5-HT levels may be a model for brain synthesis and release of 5-HT. PMID- 1736037 TI - ACAT activity in freshly isolated human mononuclear cell homogenates from hyperlipidemic subjects. AB - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol in human mononuclear cells (MNC). In order to assess the relationship between lipid levels and ACAT activity in circulating MNC, we measured the rate of [14C]oleoyl-CoA incorporation into cholesterol ester in freshly isolated MNC homogenates from hyperlipidemic subjects. Baseline, off treatment results obtained in 14 hypertriglyceridemic subjects (eight type IV and six type III) and seven subjects with familial hypercholesterolemia (FH) due to the same deletion of greater than 10 kb on the low-density lipoprotein (LDL) receptor gene were compared with values determined in 12 healthy normolipidemic subjects. The rate of cholesterol esterification was 45 +/- 28 pmol/5 min/mg cell protein in healthy normolipidemic controls. This rate was significantly higher in type IV subjects (84 +/- 52 pmol/5 min/mg cell protein, P less than .05) and FH subjects (67 +/- 25 pmol/5 min/mg cell protein, P less than .05). The values were more dispersed in type III subjects; the mean value for the group (72 +/- 46 pmol/5 min/mg cell protein) was not statistically different from the control. Hypertriglyceridemic patients were then treated with 6 g/d of omega-3 fatty acids. This resulted in a significant reduction in plasma total triglycerides and very-low-density lipoprotein (VLDL)-cholesterol in both type III subjects (-57% and -51%, P less than .05) and type IV subjects (-62% and -62%, P less than .01). The reduction in VLDL concentration was associated with a significantly lower ACAT activity in MNC homogenates from type IV subjects (from 84 +/- 52 to 60 +/- 36 pmol/5 min/mg cell protein, P less than .05), but not from type III hypertriglyceridemic subjects (from 72 +/- 46 to 73 +/- 36 pmol/5 min/mg cell protein). In conclusion, we found that cholesterol esterification in human MNC is elevated in hyperlipidemic subjects and can be decreased with normalization of lipid levels. However, ACAT activity changes occurring with treatment are heterogeneous among hyperlipidemic subjects, suggesting that factors other than plasma lipid level reduction affect ACAT activity in vivo. PMID- 1736038 TI - Prevalence of carnitine depletion in critically ill patients with undernutrition. AB - The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736039 TI - Dose-response studies on the metabolic effects of a growth hormone pulse in humans. AB - Whereas the lipolytic and diabetogenic consequences of sustained growth hormone (GH) exposure are well described, the metabolic effects of a short-lived physiological GH pulse have only recently been reported. To assess the possible dose-response of such short-term bolus administration of GH, six healthy, male subjects were each studied thrice for 4 1/2 hours after an intravenous (IV) bolus of either 70, 140, or 350 micrograms GH, resulting in peak GH concentrations of 10, 15, and 34 micrograms/L. Observed results include: (1) Time- (but not dose-) dependent changes (P less than .05) in plasma glucose and an acute (from 10 minutes onward), persistent, 40% decrease in forearm glucose uptake. Total glucose turnover decreased steadily with time on all occasions. (2) Time- and dose-dependent increases (P less than .05) in the concentrations of circulating lipid intermediates, with an increase of 3-hydroxybutyrate (3-OHB) from a basal of 35 mumol/L to peak values of 108 +/- 34 (70 micrograms), 176 +/- 46 (140 micrograms), and 232 +/- 51 mumol/L (350 micrograms), forearm uptake of 3-OHB changed in parallel. (3) Respiratory exchange ratio decreased (P less than .05) with increasing GH doses (indicating increased lipid and decreased glucose oxidation), and energy expenditure remained unaffected. (4) Concentrations of insulin, C-peptide, and glucagon were unchanged throughout all studies. We conclude that the stimulating effects of a modest GH bolus on circulating lipid intermediates and lipid oxidation are dose-dependent. This finding underlines the potential role of GH as a principal physiological regulator of fuel consumption in the maintenance of metabolic homeostasis. PMID- 1736040 TI - Skeletal muscle is a major site of lactate uptake and release during hyperinsulinemia. AB - During conditions of increased glucose disposal, plasma lactate concentrations increase due to an increase in plasma lactate appearance. The tissue sites of the elevated lactate production are controversial. Although skeletal muscle would be a logical source of this lactate, studies using the limb net balance technique have failed to demonstrate a major change in net lactate output when plasma glucose disposal is increased. Because the limb balance technique underestimates production of a substrate when the limb not only produces but also consumes that substrate, we infused 3-14C-lactate basally and during a hyperinsulinemic euglycemic clamp in seven normal volunteers to determine plasma lactate appearance, forearm lactate fractional extraction, and forearm lactate uptake and release. After 3 hours of hyperinsulinemia, glucose and lactate turnovers increased from basal values of 11.8 +/- 0.13 and 12.2 +/- 0.59 to 32.6 +/- 3.4 and 16.5 +/- 1.07 mumol/(min.kg), accompanied by an increase in plasma lactate from 0.88 +/- 0.07 to 1.16 +/- 0.09 mmol/L (P less than .05). Forearm lactate extraction increased from 27% +/- 2% to 38% +/- 2% (P less than .001), resulting in an increase in forearm lactate uptake from 0.65 +/- 0.09 to 1.18 +/- 0.08 mumol/(min.100 mL tissue) (P less than .001). Although forearm lactate net output decreased during hyperinsulinemia, forearm lactate production increased from 1.04 +/- 0.12 basally to 1.69 +/- 0.13 mumol/(min.100 mL). When forearm data was extrapolated to whole body, muscle could account for 41% +/- 4% of systemic lactate appearance basally and 45% +/- 4% during hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736041 TI - Physiological elevations of plasma beta-endorphin alter glucose metabolism in obese, but not normal-weight, subjects. AB - The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors. PMID- 1736042 TI - Magnetic resonance imaging of body fat of athletes compared with controls, and the oxidative metabolism of estradiol. AB - The extent of 2-hydroxylation of estradiol (E2), which yields a non-estrogenic metabolite (2-OHE1), increased significantly with decreasing subcutaneous fat (ScF)/total volume percent (TV%) and total fat (TF)/TV% evaluated by magnetic resonance imaging (MRI) for five athletes during low- and high-intensity training, and four controls. The increase in 2-hydroxylation with decreasing adiposity was associated with anovulation and amenorrhea among the athletes. PMID- 1736043 TI - Evidence against the hypothesis that hyperinsulinemia increases sympathetic nervous system activity in man. AB - To test the hypothesis that physiologic hyperinsulinemia activates the sympathetic nervous system in humans, we measured changes in plasma norepinephrine as well as epinephrine concentrations during euglycemic hyperinsulinemic clamp experiments in which normal volunteers were infused with insulin for up to 12 hours, at rates chosen to simulate the basal and postprandial hyperinsulinemia seen in insulin-resistant states. Infusions of insulin increased plasma insulin threefold (to approximately 200 pmol/L) and 15 fold (to approximately 1,000 pmol/L) in simulations of fasting and postprandial hyperinsulinemia. In neither experiment did plasma norepinephrine or epinephrine change significantly. In control experiments in which saline was infused for 12 hours, plasma epinephrine increased twofold (P less than .05), but plasma norepinephrine did not change. Therefore, we conclude that hyperinsulinemia of the magnitude seen in the insulin-resistant humans does not increase sympathetic nervous system activity. PMID- 1736044 TI - Catch-up growth following Escherichia coli infection in weanling rats. AB - Infection is detrimental to growth, making it a serious problem for both humans and animals. To explore factors responsible for the restoration of tissue protein stores following infection, we developed a model of Escherichia coli infection suitable for studies of protein metabolism in growing animals. Weanling female Sprague-Dawley rats were given a single intraperitoneal injection of E coli (approximately 10(9) colony forming units [CFU]/kg body weight); control rats were injected with vehicle alone. Two days later, infected rats had lower (P less than .05) body weight (-11%), food intake (-49%), daily nitrogen balance (-64%), and lower protein mass of gastrocnemius muscle (-21%), tibialis anterior muscle ( 23%), gastrointestinal tract (-15%), skin (-16%), and carcass (14%), compared with control rats. There was complete catch-up in terms of body weight, cumulative nitrogen balance, and carcass and tissue protein masses within 3 weeks of infection. Catch-up was achieved predominantly by increasing (P less than .05) the apparent nitrogen digestibility of the diet, thereby increasing the amount of nitrogen available to the body. Food intake did not increase and urinary nitrogen did not decrease during catch-up growth. E coli peritonitis in weanling rats provides a simple and useful model for the study of the effects of infection on growth and protein metabolism in growing animals. PMID- 1736045 TI - Impaired glucose disposal following mild hypoglycemia in nondiabetic and type I diabetic humans. AB - Insulin-mediated glucose disposal was studied immediately prior to and following moderate hypoglycemia in nondiabetic subjects and subjects with insulin-dependent (type I) diabetes mellitus (IDDM), the latter having varying epinephrine secretory capacities. Plasma insulin concentration was fixed throughout the study at approximately 300 to 400 pmol/L to avoid effects of waning insulin action and plasma glucose was clamped at either 5 mmol/L (euglycemic control) or at 3.1 mmol/L (hypoglycemic) periods of 120 minutes. Baseline (clamp 1) and postexperiment (clamp 2) periods were assessed for net glucose disposal (as a function of the exogenous glucose infusion rate) and glucose kinetics using 3H glucose. In normal subjects, glucose disposal increased progressively by 132% during control studies but only by 57% with intervening hypoglycemia (P less than .005). Similarly, 33% during hypoglycemia, P less than .025). These changes were mediated by reduction of whole-body glucose uptake (rate of glucose disappearance [Rd], [3H]-3-glucose) and metabolic clearance rates with comparable suppression of hepatic glucose production in both groups. The increase in plasma free-fatty acids (FFA) following hypoglycemia was modest but greater in subjects with IDDM (P less than .01), whereas IDDM had reduced concentrations of epinephrine (P less than .01) and glucagon (P less than .005) during hypoglycemia. In subjects with IDDM but not in normal subjects, the change in posthypoglycemia glucose disposal was inversely correlated with the increase in plasma norepinephrine (R2 = .54, P less than .004) and epinephrine (R2 = .32, P less than .04). Glucose disposal did not correlate with other counterregulatory hormones, plasma FFA, or antecedent glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736046 TI - Measurements of tissue sorbitol in diabetes mellitus: enzyme method versus gas liquid chromatography. AB - Two methods are commonly used to measure sorbitol in mammalian tissues. The first uses sorbitol dehydrogenase for a coupled enzymatic reaction; unfortunately, other polyols are also substrates for this enzyme. The second uses gas-liquid chromatography (GLC) for separation of polyols and mass quantitation of sorbitol. A comparison of these two methods for the measurement of sorbitol in duplicate samples of lens, nerve, and erythrocytes indicates that GLC of polyol acetates consistently finds less sorbitol than measured by sorbitol dehydrogenase. Erythritol, threitol, ribitol, arabitol, and galactitol are polyols found in variable quantities in these tissues, which have a variable influence on the activity of sorbitol dehydrogenase and therefore alter sorbitol quantitation with this enzyme. Moreover, there is an unidentified substance(s) that reacts with sorbitol dehydrogenase which seems to increase in association with hyperglycemia in the lens and nerve, but not in erythrocytes. The quantity of this unknown substance(s) seems to be reduced by the aldose reductase inhibitor sorbinil in erythrocytes and to a lesser extent sciatic nerve and lens. Since enzymatic sorbitol quantitation in the lens, nerve, and erythrocytes is influenced by many known and unknown factors other than sorbitol, we recommend that GLC of polyol acetates be used to measure sorbitol in biologic tissues. PMID- 1736047 TI - The value of cardiotocograph monitoring in midwifery. PMID- 1736048 TI - Malaria prevention. PMID- 1736049 TI - The gatekeeper role of general practice. PMID- 1736050 TI - Geriatric assessment by general practitioners. PMID- 1736051 TI - Isosporiasis in the aboriginal population of Queensland. AB - OBJECTIVE: To report on the endemicity of Isospora belli in Queensland. DESIGN: A 10-year retrospective survey of data from routine parasitological surveillance of Queensland Aboriginal communities, by microscopic examination of preserved faecal specimens. SETTING: The Aboriginal Health Programme of the Queensland Department of Health and Medical Services. POPULATION: Children under 15 years of age from all the Aboriginal communities of Queensland. RESULTS: Oocysts of I. belli were detected in 33 (0.2%) of a total of 17,642 faecal samples examined. CONCLUSION: Isosporiasis is endemic in the Queensland Aboriginal population. It is likely to be more common than indicated, because the infection is difficult to diagnose, and the techniques used to identify the organism were not particularly sensitive. It is predicted that isosporiasis will be recognised with increasing frequency as a cause of diarrhoea in Aboriginal and white Australians who develop AIDS. PMID- 1736052 TI - Emergency transport of critically ill children: stabilisation before departure. AB - OBJECTIVE: To provide up-to-date practical information, relevant to Australian conditions and practice, on stabilising the condition of critically ill children who need transport to a paediatric hospital. DATA SOURCES AND SELECTION: Information on current resuscitation practice was sought from relevant original articles and reviews in the recent medical literature, from textbooks and monographs published in the last 10 years. DATA SYNTHESIS AND CONCLUSIONS: A recent study found that 47% of 100 children who needed emergency interhospital transfer experienced problems which should have been preventable by greater availability to referring doctors of information on pretransport stabilisation of critically ill children. Hypoventilation, hypoxaemia and hypotension are commonly found in critically ill children before transport, as are difficulties with endotracheal tube care, sedation and analgesia. Mild physiological disturbances are likely to become severe and life-threatening during transfer unless they are corrected before departure. Early discussion of the child's problems and the transfer plan with senior staff at the nearest paediatric intensive care unit may be helpful in planning the pre-transfer resuscitation. PMID- 1736053 TI - Sex steroid hormones and breast cancer: is there a link with oral contraceptives and hormone replacement therapy? AB - OBJECTIVE: To determine whether use of sex steroid hormones for contraception and hormone replacement therapy alters the risk of breast cancer, and whether the risk varies with their composition, duration of use, the period of a woman's life when the hormones are used, and after successful treatment for breast cancer. DATA SOURCES: The results of important epidemiological reports, readily available from the English literature and published since 1981, were evaluated, using reports of basic scientific work as a background to the problem. STUDY SELECTION: An attempt was made to obtain most of the relevant reports. Twenty case-control and seven cohort studies were available on the oral contraceptive pill (OCP) and eleven case-control and five cohort studies on hormone replacement therapy (HRT). DATA EXTRACTION: The relative risk estimates for breast cancer (and their 95% confidence intervals) determined by each report were tabulated according to the specific conditions of analysis, for example users under age 25, duration of use. Results by meta-analysis from previous studies were also used to determine risk. A significant positive association was present when the risk estimate exceeded 1.0 and the 95% confidence interval did not cross 1.0. DATA SYNTHESIS: Among OCP users, the vast majority of reports showed no significant risk of breast cancer- overall, longest duration of use, and use before first full-term pregnancy. However, a positive association between breast cancer and users under age 25 was found in three of eight reports. Similarly, the majority of reports showed no significant risk of breast cancer among HRT users, overall as well as in relation to duration of use and interval since first use. There was no increased risk with additional progestogen; it may be protective. An improved prognosis was found in users who developed breast cancer. On the limited data, use of hormones for postmenopausal symptoms did not appear to be harmful to women who had been successfully treated for breast cancer. CONCLUSIONS: The review revealed good evidence that use of sex steroid hormones had no significant effect on the risk of breast cancer, whether given for contraception or hormone replacement. There was some concern about increased risk with prolonged use of the OCP, especially in younger women. At present, use of these hormones is a matter of informed choice, with individual considerations of the risk-benefit ratio. PMID- 1736054 TI - Prenatal diagnosis and successful intrauterine treatment of a female fetus with 21-hydroxylase deficiency. AB - OBJECTIVE: To present the first reported Australian case of prenatal treatment of a female fetus with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. CLINICAL FEATURES: A couple whose son had congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency sought prenatal diagnosis and treatment in their next pregnancy. INTERVENTION: Maternal treatment with dexamethasone was commenced at seven weeks' gestation to suppress androgen production by the fetal adrenal glands and prevent virilisation of an affected female fetus. At ten weeks' gestation chorionic villus sampling demonstrated a female fetus, who was shown subsequently to be affected by means of a linkage method in which probes to HLA genes DQA and DRB were used as markers for the 21 hydroxylase genes. Increased 17-hydroxyprogesterone and androstenedione immunoactivity in amniotic fluid obtained at 14.5 weeks confirmed the fetus to be affected and demonstrated incomplete suppression of fetal adrenal androgen production. Dexamethasone was continued to term and maintained suppression of the fetal and maternal adrenal glands. OUTCOME: The infant was born with normal female genitalia. Growth retardation was present but the relationship between this and the dexamethasone treatment remains uncertain. The mother had excessive weight gain during pregnancy. CONCLUSION: Dexamethasone treatment commenced in the first weeks of pregnancy can prevent or reduce virilisation of female fetuses with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. PMID- 1736055 TI - Is sarcocystosis common in Sydney? PMID- 1736056 TI - Pneumocystis thyroiditis. PMID- 1736057 TI - Availability of sleep studies. PMID- 1736058 TI - Failure to demonstrate contrast nephrotoxicity. PMID- 1736059 TI - Heterosexual transmission of HIV in Victoria: implications for contact tracing and sex tourism. PMID- 1736060 TI - Overseas medical practitioners and "racial discrimination". PMID- 1736061 TI - Ruptured abdominal aortic aneurysms: does an incorrect initial diagnosis prejudice survival? PMID- 1736062 TI - Gregg's rubella legacy 1941-1991. PMID- 1736063 TI - Depo-Medrol. PMID- 1736064 TI - Flying obstetric and gynaecology service--rural anaesthesia. PMID- 1736065 TI - General practitioners and over-servicing. PMID- 1736066 TI - Terminal restlessness--its management and the role of midazolam. PMID- 1736067 TI - Intranasal meningoencephalocele causing recurrent meningitis in a 25-year-old Caucasian man. PMID- 1736068 TI - Spiroplasmas and spongiform encephalopathies. PMID- 1736069 TI - The biological significance of dioxins and other organochlorines. PMID- 1736070 TI - Attempted suicide in Adelaide and Perth. PMID- 1736071 TI - Failure of 500 mg ciprofloxacin therapy in male urethral gonorrhoea. PMID- 1736072 TI - Surrogate therapy for sexual dysfunction. PMID- 1736073 TI - Vacuum devices in the treatment of impotence. PMID- 1736075 TI - An epidemiological study of snake bite envenomation in Papua New Guinea. PMID- 1736074 TI - Endometrial ablation or hysterectomy? PMID- 1736077 TI - Lead: subtle forms and new modes of poisoning. PMID- 1736076 TI - Hypophosphataemia in a comatose alcoholic. PMID- 1736078 TI - Firearms legislation and suicide. PMID- 1736079 TI - Boxing. PMID- 1736080 TI - Women, cardiovascular disease and hormone replacement therapy. PMID- 1736081 TI - Firearms suicides in Australia. AB - OBJECTIVE: To examine the rates of suicide by firearms in the five larger Australian States during 1968-1989, and to relate them to differences between those States. We hypothesised that (i) restrictive gun legislation will have reduced the firearms suicide rate in South Australia after 1980, and (ii) firearms suicides would be shown to be more common in States with larger rural:urban population ratios. DESIGN: Data supplied by the Australian Bureau of Statistics were analysed by sex, State and year of suicide. Differences between the firearms suicide rates of capital city and rural dwellers, and of different age-groups, were recorded. RESULTS: Firearms suicide rates in South Australia declined significantly after 1980, following proclamation of gun legislation, in contrast to the four other larger States where an increase in firearms suicides was recorded. The firearms suicide rate in Queensland has remained consistently higher than in the other four larger States during 1968-1989. The number of Australian firearms suicides per year fell by 25% from a peak of 572 in 1987 to 451 in 1989. CONCLUSIONS: Further reductions in the Australian firearms suicide rate might be achieved by tightening gun laws and by a media campaign aimed at reducing easy access by males to guns in rural households. PMID- 1736082 TI - Youth suicide in New South Wales: urban-rural trends. AB - OBJECTIVE: The study tested the hypotheses that (i) the rate of suicide by firearms among youth (aged 10-19 years) is increasing at a greater rate than rates of suicide by other methods; (ii) the rate of youth suicide in rural New South Wales is significantly higher than those in urban areas; and (iii) the increase in youth suicide by means of firearms is occurring at a greater rate in rural males aged 15-19 years than in other groups. DESIGN: Data were obtained from the NSW Office of the Australian Bureau of Statistics concerning 735 youth suicides in NSW between 1964 and 1988. These were reviewed for information concerning residential area and method of death. Five five-year periods were used, and rates were calculated with population figures obtained in the census years for the same age and sex group. RESULTS: From 1964 to 1988, suicide by firearms has risen most substantially, from 3.4 to 5.6 per 100,000 per year in 15 19-year-old males. There has also been a substantial increase in 15-19-year-old male suicides by hanging (0.7 to 3.4 per 100,000 per year). Poisoning suicides have declined among females and males in the past 15 years. Suicide rates in Sydney, Newcastle and Wollongong have remained stable. In rural cities, they have increased from 1.5 to 4.7 per 100,000 per year (F = 4.9, P less than 0.02) while in rural municipalities and shires they have increased from 1.3 to 6.4 (F = 14.6, P less than 0.0001). The suicide rate of 15-19-year-old males has shown a modest increase in Sydney and no change in Newcastle or Wollongong, but the rate for 15 19-year-old males in rural cities has more than doubled, from 5.1 to 12.5 (F = 7.7, P less than 0.003), while in rural municipalities and shires, the rate has increased more than fivefold, from 3.9 to 20.7 (F = 9.3, P less than 0.001). There has been no significant change in the suicide rates of 15-19-year-old females, or in 10-14-year-olds. The rate of suicide by firearms among 15-19-year old males has not risen significantly in rural cities, but in rural municipalities and shires the rates have risen fivefold from 2.8 to 14.8 (F = 5.6, P less than 0.01). CONCLUSIONS: Each hypothesis was confirmed. An increase of this magnitude is not an artefact of coroners' verdicts. The findings are believed to be due to ready access to firearms, the use of alcohol and drugs (particularly in firearms suicides) and increasing socioeconomic, health, and identity problems for rural youth, especially males. PMID- 1736083 TI - Percutaneous aortic valvuloplasty. AB - OBJECTIVE: To determine the short-term and long-term results of percutaneous aortic valvuloplasty. DESIGN: A retrospective follow-up study. SETTING: The Cardiac Catheterisation Laboratory and Cardiovascular Medicine Unit of a teaching hospital. PATIENTS: Eighteen patients with severe aortic stenosis who were not accepted for surgery; there were 11 men and 7 women, mean age 79 +/- 4.5 years. INTERVENTIONS: Percutaneous transluminal aortic valvuloplasty (PTAV) by means of balloon catheter techniques. MAIN OUTCOME MEASURES: Patient survival and symptomatic status. RESULTS: PTAV resulted in a significant decrease in the aortic valve pressure gradient from 64.8 +/- 23.2 mmHg to 38 +/- 14.7 mmHg (mean +/- SD) (P less than 0.00001) in the 18 patients and a significant increase in the mean aortic valve area from 0.4 +/- 0.16 cm2 to 0.6 +/- 0.18 cm2 (P less than 0.0001) in 14 patients. Complications occurred in seven patients; two of them, who had been in terminal heart failure with a low output state before PTAV, died. Fifteen patients improved in at least one New York Heart Association functional class early after PTAV and one patient had an aortic valve replacement. In follow up of between 5 and 32 months (mean, 13.3 +/- 7.7 months) six patients are in a better functional class than before PTAV, one patient is in Class IV, one patient had an aortic valve replacement and seven patients died (three died of cardiac failure and four of non-cardiac causes). CONCLUSIONS: PTAV has a place as a palliative procedure in selected patients with aortic stenosis in whom another condition precludes aortic valve replacement. PMID- 1736084 TI - Promotion of attendance for mammographic screening through general practice: a randomised trial of two strategies. AB - OBJECTIVE: To compare the effectiveness of two strategies--patient education and practitioner recommendation--in encouraging women to attend for mammographic screening. DESIGN: The study was a prospective randomised controlled trial. Women aged between 40 and 70 years attending a general practitioner participated in the study. Consenting, eligible women were randomly allocated to one of the two strategy groups. SETTING: The study was conducted in private general practice in Newcastle, New South Wales. PARTICIPANTS: The general practitioners who took part in the study were a non-random sample of practitioners: 20 were approached, two declined to participate, and five failed to begin recruitment, leaving 13 practitioners who took part in the study. A total of 302 women aged 40-69 were recorded as attending the surgeries during recruitment sessions. Twenty women did not consent to the study and 73 were ineligible. Thirty-four women were not given the intervention because the general practitioner forgot or did not have time. There were 92 women in the simple recommendation group and 83 women in the patient education group. INTERVENTIONS: An intensive patient education approach based on health belief principles was compared with a simple recommendation by the general practitioner that the woman have a mammogram. MAIN OUTCOME MEASURE: Attendance rates were calculated from screening service attendance records. RESULTS: No significant difference in attendance rates was observed between the two groups, 82% of the simple recommendation group and 91% of the patient education group attended for screening. CONCLUSIONS: These results suggest that mammographic screening can be effectively promoted in general practice without extensive patient education. PMID- 1736085 TI - Prevalence of intellectual handicap in Western Australia: a community study. AB - OBJECTIVE: To produce comprehensive community based data on individuals with intellectual handicap, the level of retardation, associated handicaps and demographic data. DESIGN: Multiple sources of ascertainment were used to identify all children in birth cohorts, 1967-1976 inclusive, who had an IQ less than 70. SETTING: The majority of cases were ascertained through Western Australian government agencies that provide services for the intellectually handicapped. Other sources included the support branch of the education department, private schools and the children's hospital. PATIENTS: In all, 1602 children, aged between 6 and 16 years, fitted the study criteria. RESULTS: The prevalence of intellectual handicap was found to be 8.9 per 1000 live male births and 6.3 per 1000 live female births with an overall rate of 7.6. The figures for mild, moderate, severe and profound retardation were 3.0, 2.4, 1.0 and 0.6 per 1000, respectively, with 0.8 per 1000 with an unknown IQ. Cerebral palsy occurred in 20% and epilepsy in 13% in addition to intellectual handicap. There was a significantly higher rate among those from rural compared with urban areas: 9.9 v. 6.5 per 1000 live births, respectively. CONCLUSIONS: This comprehensive epidemiological data on intellectual handicap in Western Australia will be of value in the planning of services, including screening and genetic counselling, and for the evaluation of care. The rural preponderance, in particular, is worthy of further evaluation. PMID- 1736086 TI - Measles at an international gymnastics competition--Indiana, 1991. AB - On September 7, 1991, the Indiana State Department of Health (ISDH) was notified of three suspected measles cases among athletes from New Zealand (NZ) participating in an international gymnastics competition September 6-15 in Indianapolis (Marion County). Among those potentially at risk for measles were approximately 700 athletes and 1200 coaches, trainers, and managers from 51 countries; an estimated 2500 volunteers and staff; international media, families, and employees; and approximately 60,000 spectators attending the competition. This report summarizes the epidemiologic investigation of these cases. PMID- 1736087 TI - Safety-belt and helmet use among high school students--United States, 1990. AB - During 1988, injuries were the leading cause of death among persons aged 15-19 years in the United States. More than half (53%) of these deaths were motor vehicle related, including crashes involving bicycles and motorcycles with motor vehicles (CDC, unpublished data, 1988). Among persons aged 15-19 years, motor vehicle-related injuries are the leading contributor to hospital and emergency department medical costs associated with injuries (1). This article presents 1990 self-reported data from U.S. students in grades 9-12 regarding the prevalence of three behaviors that reduce the risk for injuries from motor-vehicle crashes safety-belt use, motorcycle-helmet use, and bicycle-helmet use. PMID- 1736088 TI - Eastern equine encephalitis virus associated with Aedes albopictus--Florida, 1991. PMID- 1736089 TI - Mortality patterns--United States, 1989. AB - During 1989, 2,150,466 deaths were registered in the United States--17,533 fewer deaths than the record-high number recorded in 1988. In 1989, as for at least the past 20 years, nearly three fourths of deaths were attributable to the first four leading causes of death--heart disease, cancer, stroke, and unintentional injury. This report summarizes mortality data compiled by CDC's National Center for Health Statistics (NCHS) for 1989 (1) and compares patterns with 1988. PMID- 1736090 TI - Transcription in vivo within the replication origin of the Escherichia coli chromosome: a mechanism for activating initiation of replication. AB - Within the replication origin, oriC, of the Escherichia coli chromosome, novel in vivo transcripts were detected which proceeded rightward and whose production was activated by DnaA protein. In contrast, DnaA protein repressed the previously described ori-L leftward transcription. The former should introduce negative supercoiling, and the latter positive supercoiling, into the 13-mers. The effects of transcription on the initiation of replication were also investigated by making constructs with promoters placed near oriC. Transcription was found to enhance the origin activity only when it was oriented in such a way as to introduce negative supercoiling into the 13-mers. From these results, we propose that transcription within oriC regulates replication initiation by altering the topology of the 13-mer region. PMID- 1736091 TI - Molecular structure of the DNA cross-link repair gene SNM1 (PSO2) of the yeast Saccharomyces cerevisiae. AB - A 3.2 kb yeast DNA fragment containing the DNA interstrand cross-link-specific repair gene SNM1 has been sequenced. Two genes were identified. SNM1 has an open reading frame of 1983 bp and codes for a 661 amino acid protein. Hydrophobic analysis shows that the protein is most probably not directly membrane bound. The second gene, UGX1, has an open reading frame of 573 bp coding for a polypeptide of 191 amino acid residues. The two genes are arranged head to head and share a 192 bp divergent promoter region that contains three TATAAA motives, two for the SNM1 and one for the UGX1 locus. Gene UGX1 has no apparent influence on the sensitivity of the cell to cross-linking nitrogen mustard, as its disruption in wild type does not increase sensitivity to nitrogen mustard and the presence of multiple copies of the gene fails to complement the nitrogen mustard sensitivity phenotype of snm1 disruption mutants. Northern analysis revealed that the expression of SNM1 yields an average of 0.3 copies/cell of a 2.4 kb transcript, while expression of UGX1 yields higher levels of a 0.8 kb poly(A)+ RNA. PMID- 1736092 TI - An intragenic map of the brlA locus of Aspergillus nidulans. AB - We have constructed an intragenic map for the Aspergillus nidulans brlA gene, mutants in which are distinguishable by visual criteria only. Most of the leaky phenotype mutants map near the right (3') end. The gene shows distinct recombinational polarity consistent with recombination initiation at the promoter (centromere-proximal) end of the gene. brlA12 and brlA20 mutants gave abnormal DNA restriction patterns consistent with the III; VIII and VI; VIII translocations, respectively, determined by haploidization. PMID- 1736093 TI - Synergistic effect of upstream sequences, CCAAT box elements, and HSE sequences for enhanced expression of chimaeric heat shock genes in transgenic tobacco. AB - The thermoregulated expression of the soybean heat shock (hs) gene Gmhsp17.3-B is regulated via the heat shock promoter elements (HSEs), but full promoter activity requires additional sequences located upstream of the HSE-containing region. Structural features within this putative enhancer region include a run of simple sequences which are also present upstream of HSE-like sequences of other soybean hs genes, and three perfect CCAAT box sequences located immediately upstream from the most distal HSE of the promoter. A series of heterologous and homologous promoter fusions linked to the chloramphenicol acetyl transferase (CAT) gene was constructed and examined in transgenic tobacco plants. The region containing the AT-rich domain of the 5' flanking region was unable to direct transcription from the TATA box of a truncated delta CaMV35S promoter. Heat-inducible CAT activity was detectable when additional sequences from the native promoter containing three CCAAT boxes and a single HSE were present in the constructions. Complete reconstitution of the native hs promoter/enhancer region increased hs specific CAT activities only very little, but deletion of CCAAT box sequences reduced CAT expression five-fold. Our results suggest that AT-rich sequences have a moderate effect on thermoinducible expression levels of the soybean heat shock gene and that CCAAT box sequences act cooperatively with HSEs to increase the hs promoter activity. PMID- 1736094 TI - Transformation frequencies are enhanced and vector DNA is targeted during retransformation of Leptosphaeria maculans, a fungal plant pathogen. AB - Leptosphaeria maculans, a fungal pathogen of Brassica spp., was successfully transformed with the vector pAN8-1, encoding phleomycin resistance. Protoplasts of a vigorous Phleor transformant were then retransformed using the partially homologous vector, pAN7-1 which encodes hygromycin B resistance. Retransformation of this strain to hygromycin resistance occurred at frequencies that were consistently twofold higher than with the original recipient strain. Linearised pAN7-1 DNA transformed phleomycin-resistant protoplasts at higher frequencies still. All the transformants that were tested retained a phleomycin-resistant phenotype (20/20). Molecular analysis of five transformants generated with circular pAN7-1 DNA indicated that in four cases the pAN7-1 vector had integrated into pAN8-1 sequences. These results suggest that transformation frequencies in L. maculans are limited by the ability of vector DNA to integrate into the genome. Hence, construction of strains with target sites for integration may prove to be a generally useful method for improving transformation frequencies of poorly characterised filamentous fungi, particularly when using heterologous vectors. This would greatly facilitate the identification of genes by transfer of gene libraries and the standardisation of chromosomal location effects in studies of expression of nested promoter deletions. PMID- 1736095 TI - In vitro interactions of integration host factor with the ompF promoter regulatory region of Escherichia coli. AB - Previous work has shown that integration host factor (IHF) mutants have increased expression and altered osmoregulation of OmpF, a major Escherichia coli outer membrane protein. By in vitro analysis the possibility was investigated that IHF interacts directly with the ompF promoter region. Gel retardation assays and DNase I protection experiments showed that IHF binds to two sites in the ompF promoter region centered at positions -180 and -60 relative to the start of transcription. Gel electrophoresis studies with circularly permuted ompF promoter fragments indicated that IHF binding strongly increased a small intrinsic bend in the ompF promoter region. The addition of IHF to a purified in vitro transcription system strongly and specifically inhibited ompF transcription. This inhibition was reversed by increasing the concentration of OmpR, a positive activator required for ompF expression, suggesting that IHF may inhibit ompF transcription by altering how OmpR interacts with the ompF promoter. PMID- 1736096 TI - Regulation of the gua operon of Escherichia coli by the DnaA protein. AB - The guaBA operon determines production of the two enzymes required to convert hypoxanthine to guanine at the nucleotide level during guanine nucleotide biosynthesis. Two DnaA boxes, binding sites for the DNA replication-initiating DnaA protein, are present in the gua operon, one at the gua promoter (guaP) and the other within the guaB coding sequence. Regulation of the guaBA operon by DnaA protein was studied using strains carrying chromosomal gua-lacZ fusions. In these strains beta-galactosidase acts as a reporter enzyme for transcription initiated at guaP. When the intracellular levels of DnaA were increased (by induction of a multicopy plasmid carrying the dnaA gene fused to the tac promoter) transcription from the gua promoter was repressed. Reducing the intracellular level of DnaA, either by sequestration with an oriC plasmid or by placing a temperature sensitive dnaA mutant at the restrictive temperature, resulted in increased transcription from guaP. Thus the transcriptional activity of the gua operon is coupled, through the DnaA protein, to the DNA replication cycle. Repression of guaP by DnaA was dependent on the presence of both boxes in the gua-lacZ fusion; constructs containing only the box at guaP were unaffected by DnaA. PMID- 1736097 TI - A plant histone gene promoter can direct both replication-dependent and independent gene expression in transgenic plants. AB - Chimeric genes containing the beta-glucuronidase (GUS) gene under the control of different Arabidopsis histone H3 and H4 promoters were found to be highly expressed in transient expression experiments using tobacco protoplasts. The activity of one of these promoters, H4A748, was further analyzed. The kinetics of H4A748-GUS activity are very similar to these of a CaMV 35S-GUS constitutive gene during protoplast culture. No increase in H4A748-GUS activity was found after 24 h of protoplast culture when DNA synthesis starts, nor was the GUS activity affected when an inhibitor of DNA synthesis was included in the culture medium. This failure to detect any replication-dependent activity is most likely to be due to the fact that transient transcription of the introduced construct is restricted to the first 24 h following transfection. Stable integration of the H4A748-GUS gene into tobacco plants showed that the histone promoter could confer increased expression in meristematic tissues but it is also expressed to significant levels in non-proliferating tissues. Protoplasts prepared from these transgenic tobacco plants were cultivated under different conditions that affect DNA synthesis. Analysis of H4A748-GUS activity revealed (i) the existence of a basal replication-independent activity and (ii) a replication-dependent activity induced in parallel with DNA synthesis. These results show that the histone H4 promoter is able to direct both replication-dependent and -independent gene expression. PMID- 1736098 TI - Cell-free transcription of the nifH1 gene of Methanococcus thermolithotrophicus indicates that promoters of archaeal nif genes share basic features with the methanogen consensus promoter. AB - The nifH1 gene of Methanococcus thermolithotrophicus, which encodes the putative dinitrogenase reductase of an archaeon, was accurately transcribed in a homologous cell-free transcription system. Extracts of cells grown with N2 or ammonia as nitrogen source initiated transcription at the nifH1 promoter with similar efficiencies. We confirmed that cells grown under non-N2-fixing conditions do not contain significant amounts of nifH1-specific mRNA. The levels of cell-free transcription initiation at the nifH1 promoter were similar to those observed at a tRNA promoter. The DNA sequence from -40 to +5 relative to the initiator nucleotide of nifH1 mRNA contained all the information required for promoter activity. A mutational analysis of this section of DNA demonstrated that a TATA box at -25 and the TTGT motif (initiator element) at the transcription start site are essential for cell-free transcription. These elements are similar to the structural determinants of a known tRNA promoter of Methanococcus. Mutation of a sequence, showing homology to the bacterial NifA site, which overlaps the transcription start site, did not affect promoter activity. Hence, cell-free transcription of the Methanococcus nifH1 gene is independent of upstream activator elements and does not require alternate cis-acting sequences that differ from the methanogen consensus promoter. These findings suggest that the activation of nif promoters is brought about by fundamentally different mechanisms in Archaea and bacteria. PMID- 1736099 TI - Genomic organization of an alpha-zein gene cluster in maize. AB - The genes encoding the alpha-zein proteins of maize constitute a large multigene family of some 75 genes. This multigene family can be divided into four subfamilies based on the nucleotide sequences of their genes and the deduced amino acid sequences of their proteins. We describe for the first time evidence of a clustering of five alpha-zein subfamily 4 (SF4) genes that are members of one of the major alpha-zein subfamilies in a 56 kb region of the genome of the maize inbred line W22. None of the other three known alpha-zein gene subfamilies (SF1, SF2, or SF3) are present in this cluster. The genomic region was reconstructed using restriction endonuclease maps to identify and align three overlapping cosmid clones isolated from a genomic library. The alpha-zein genes are not evenly spaced; the minimum distance between genes is 3.5 kb; the maximum is 13 kb. All the alpha-zein genes in the cluster have the same transcriptional orientation. The location and sequences of some of the repetitive DNA elements in this gene cluster were determined. We estimate that there are a minimum of eight repetitive DNA elements in this region. The sequences of the repetitive elements (not functionally defined) are located between or among the alpha-zein genes. The regions containing two of these repetitive elements (Rep1 and Rep4) have been sequenced; they are about 15 kb apart in the genome. These repetitive elements have similar sequences for about 300 bp out of the 400 bp compared. The regions of sequence similarity, however, are in reverse orientation to one another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736100 TI - Cloning of a superoxide dismutase gene from Listeria ivanovii by functional complementation in Escherichia coli and characterization of the gene product. AB - A gene encoding superoxide dismutase (EC 1.15.1.1., SOD) was isolated from a plasmid library of chromosomal DNA from Listeria ivanovii by functional complementation of an SOD-negative Escherichia coli host. The nucleotide sequence of the cloned gene was determined and contained an open reading frame which codes for a protein of 202 amino acid residues (calculated molecular weight 22755 Da including the amino-terminal methionine residue). Comparison of the deduced amino acid sequence of L. ivanovii SOD with previously reported SOD amino acid sequences revealed considerable homologies with Fe- and Mn-dependent SODs. Enzymatic analyses using cell lysates and the purified recombinant enzyme indicated that this SOD is manganese-dependent. The recombinant SOD accounted for up to 30% of the total soluble protein in recombinant E. coli and protected sodA sodB mutants against the toxic effects of paraquat. Subunits of the recombinant Listeria SOD and of both E. coli SODs formed enzymatically active hybrids in vivo. PMID- 1736101 TI - Transcriptional analysis and promoter mapping of the fdxA gene which encodes the 7Fe ferredoxin (FdII) of Rhodobacter capsulatus. AB - The structural gene (fdxA) coding for ferredoxin II (FdII) of the photosynthetic bacterium Rhodobacter capsulatus has been previously cloned and sequenced. Transcription of the fdxA gene was studied by mRNA analyses and by use of plasmid borne fdxA::lacZ translational fusions. The transcription start site was mapped 23 bp upstream of the initiation codon, as deduced from analysis of mRNA by mung bean nuclease protection and primer extension experiments. A motif resembling the canonical sequence observed in sigma 70-dependent Escherichia coli promoters is present at the expected distance (-10/-35) from the proposed transcription start site. mRNA analysis by Northern hybridization revealed a fdxA-specific transcript of approximately 0.4 kb, indicating that fdxA is transcribed as a single gene.fdxA expression, as measured by the activity of the fdxA::lacZ fusion, was found to be constant during growth and reached a similar level under all growth conditions tested. These results suggest that FdII is constitutively synthesized in R. capsulatus. PMID- 1736102 TI - The CDC26 gene of Saccharomyces cerevisiae is required for cell growth only at high temperature. AB - We have cloned and sequenced the wild-type CDC26 gene and a mutant allele, cdc26 1, of Saccharomyces cerevisiae. Nucleotide sequence analysis revealed that the gene we cloned was the same as SCD26, a dosage-dependent suppressor of cdc26. However, the cloned gene is in fact the CDC26 gene, because a nucleotide substitution in cdc26-1 was found to be a nonsense mutation in this sequence. Disruption of this gene conferred thermosensitive cell growth and the disrupted cdc26 gene could not complement the cdc26-1 mutant allele. Thus, the CDC26 gene is required for cell growth only at high temperature. PMID- 1736103 TI - A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. AB - BACKGROUND: The efficacy of sigmoidoscopic screening in reducing mortality from colorectal cancer remains uncertain. A randomized trial would be ideal for clarifying this issue but is very difficult to conduct. Case-control studies provide an alternative method of estimating the efficacy of screening sigmoidoscopy. METHODS: Using data on the 261 members of the Kaiser Permanente Medical Care Program who died of cancer of the rectum or distal colon from 1971 to 1988, we examined the use of screening by rigid sigmoidoscopy during the 10 years before the diagnosis and compared it with the use of screening in 868 control subjects matched with the case subjects for age and sex. RESULTS: Only 8.8 percent of the case subjects had undergone screening by sigmoidoscopy, as compared with 24.2 percent of the controls (matched odds ratio, 0.30; 95 percent confidence interval, 0.19 to 0.48). Adjustment for potential confounding factors increased the odds ratio to 0.41 (95 percent confidence interval, 0.25 to 0.69). The negative association was as strong when the most recent sigmoidoscopy was 9 to 10 years before diagnosis as it was when examinations were more recent. By contrast, for 268 subjects with fatal colon cancer above the reach of the sigmoidoscope and for 268 controls, the adjusted odds ratio was 0.96 (95 percent confidence interval, 0.61 to 1.50). The specificity of the negative association for cancer within the reach of the sigmoidoscope is consistent with a true efficacy of screening rather than a confounding by unmeasured selection factors. CONCLUSIONS: Screening by sigmoidoscopy can reduce mortality from cancer of the rectum and distal colon. A screening once every 10 years may be nearly as efficacious as more frequent screening. PMID- 1736104 TI - Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. AB - BACKGROUND AND METHODS: Surveillance by repeated colonoscopy is currently recommended for patients with colorectal adenomas. We assessed the long-term risk of colorectal cancer after rigid-instrument sigmoidoscopy and polypectomy in 1618 patients with rectosigmoid adenomas (tumor of the rectum or distal sigmoid colon) who did not undergo surveillance. A total of 22,462 person-years of observation were accrued (mean, 14 years per patient). RESULTS: The incidence of subsequent rectal cancer in these patients was similar to that in the general population (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.7 to 2.1). Most rectal cancers developed in patients whose adenomas had been inadequately removed; the risk was very low after complete removal. The risk of subsequent colon cancer depended on the histologic type, size, and number of adenomas in the rectosigmoid. Among 842 patients with a rectosigmoid adenoma that was tubulovillous, villous, or large (greater than or equal to 1 cm), colon cancer developed in 31 patients. The standardized incidence ratio was 3.6 (95 percent confidence interval, 2.4 to 5.0) overall and 6.6 (95 percent confidence interval, 3.3 to 11.8) if there were multiple rectosigmoid adenomas. Among the remaining 776 patients with only small, tubular adenomas (whether single or multiple), colon cancer developed in only 4 patients. The standardized incidence ratio in this group was 0.5 (95 percent confidence interval, 0.1 to 1.3). CONCLUSIONS: Follow-up colonoscopic examinations may be warranted in patients with tubulovillous, villous, or large adenomas in the rectosigmoid, particularly if the adenomas are also multiple. In patients with only a single, small tubular adenoma that is only mildly or moderately dysplastic (43 percent of our series), however, surveillance may not be of value because the risk of cancer is so low. PMID- 1736105 TI - Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy. AB - BACKGROUND: Patients who have insulin-dependent diabetes mellitus and nephropathy have an excess of cardiovascular disease. Familial factors may in part account for this phenomenon. METHODS: We identified 61 white patients under 65 years of age with insulin-dependent diabetes who had nephropathy, and then matched them with 61 diabetic patients without nephropathy. We determined the prevalence of cardiovascular disease in the parents of these patients with use of information obtained from death certificates or from the World Health Organization questionnaire for cardiovascular disease. RESULTS: The rates of ascertainment of information were 96 percent (n = 117) for the parents of diabetic patients with nephropathy and 95 percent (n = 116) for the parents of patients without nephropathy. Cardiovascular disease was more often a direct cause of death among the parents of diabetic patients with nephropathy (40 percent vs. 22 percent, P less than 0.03), and the combined morbidity and mortality from cardiovascular disease in this group was greater than that in the parents of diabetic patients without nephropathy (31 percent vs. 14 percent, P less than 0.01). The age adjusted and sex-adjusted relative risk of cardiovascular disease in this group of parents was 2.9 (95 percent confidence interval, 1.5 to 5.5; P less than 0.001). Moreover, a paternal history of cardiovascular disease was associated with a significantly increased risk of nephropathy in the diabetic patient after the analysis was adjusted for age, sex, and duration of diabetes (odds ratio, 3.2; 95 percent confidence interval, 1.3 to 7.9; P less than 0.01). Among the diabetic patients with nephropathy, those who had had a cardiovascular event were much more likely to have a family history of cardiovascular disease (odds ratio, 6.2; 95 percent confidence interval, 2.0 to 19.0; P less than 0.005) than those who had not had such an event. CONCLUSIONS: Among patients with insulin-dependent diabetes, a parental history of cardiovascular disease is significantly associated with the development of nephropathy and, among those with nephropathy, increases the likelihood of cardiovascular disease. PMID- 1736106 TI - Hodgkin's disease. PMID- 1736107 TI - How sure is sure enough? PMID- 1736108 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1992. A 41-year-old woman with a swollen left leg, pelvic mass, and bilateral hydronephrosis. PMID- 1736109 TI - Screening sigmoidoscopy for colorectal cancer. PMID- 1736110 TI - The new tuberculosis. PMID- 1736111 TI - Postmenopausal estrogen therapy and cardiovascular disease. PMID- 1736112 TI - Postmenopausal estrogen therapy and cardiovascular disease. PMID- 1736113 TI - Postmenopausal estrogen therapy and cardiovascular disease. PMID- 1736114 TI - Postmenopausal estrogen therapy and cardiovascular disease. PMID- 1736115 TI - Fetal fibronectin and preterm labor. PMID- 1736116 TI - Circadian variation in vascular tone. PMID- 1736117 TI - Circadian variation in vascular tone. PMID- 1736118 TI - Response of refractory thrombotic thrombocytopenic purpura to extracorporeal immunoadsorption. PMID- 1736119 TI - Contractile properties of the diaphragm. PMID- 1736120 TI - Contractile properties of the diaphragm. PMID- 1736121 TI - Physicians and occupational medicine. PMID- 1736122 TI - Physicians and occupational medicine. PMID- 1736123 TI - Physicians and occupational medicine. PMID- 1736124 TI - Shortages of antimycobacterial drugs. PMID- 1736125 TI - [A prospective study of the effectiveness of thermal bath treatments in patients with rheumatoid arthritis]. PMID- 1736126 TI - [Cell biology from a medical viewpoint. XI. Peroxisomes: unmasking of a hidden organelle by studies of the Zellweger syndrome]. PMID- 1736127 TI - [Vaccination against influenza; encourage it or adopt a wait and see attitude?]. PMID- 1736128 TI - [No difference in effectiveness measured between treatment in a thermal bath and in an exercise bath in patients with rheumatoid arthritis]. AB - OBJECTIVE: To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath. DESIGN: Controlled therapeutic trial. SETTING: The thermomineral institution at Arcen and the exercise bath at the Maasland Hospital in Sittard, the Netherlands. PATIENTS AND METHODS: 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist, according to a standardized exercise-scheme: 27 were treated in the thermomineral institution and 19 (control-group) in the hospital exercise bath. Each patient received 12 treatments in 12 weeks. ENDPOINTS PARAMETERS: Morning stiffness, erythrocyte sedimentation rate, Ritchie index, amount of pain, answers to 11 questions concerning the activities of daily life, and psychosocial aspects of the disease. The various subjective and objective parameters were scored by the same physician. RESULTS: Statistically significant improvement was observed in both groups concerning morning stiffness. Other subjective parameters improved, but did not reach significance. Objective parameters did not change significantly. Between-group differences were not found. CONCLUSION: Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis, whether it is applied in a thermomineral institution or an ordinary hospital exercise bath. PMID- 1736129 TI - [Opinions of family physicians and specialists on vaccination against influenza]. AB - About 50 percent of the patients who because of an underlying disease should be vaccinated annually against influenza, do not receive the vaccine. One of the major reasons is that they are not informed by their physicians about the need to be vaccinated. To understand the attitude of the physicians concerning influenza vaccination and the way the vaccination of these patients is organized, questionnaires were send to 250 general practitioners, 125 cardiologists and 125 pulmonologists in the Netherlands. Eighty-four percent of the questionnaires were returned. The results show that the physicians were well informed about the indications for vaccination. A minority of the physicians had doubts about the efficacy of the vaccine. Both specialists and general practitioners agreed that vaccination should be performed by the general practitioner. Instruction of the patients and application of the vaccine were generally rather well organized. It is to be expected, however, that improvement of the organization will enhance the rate of vaccination against influenza in the Netherlands. PMID- 1736130 TI - [Implementation of influenza vaccination in 3 hospitals]. AB - In two general hospitals and one university hospital questionnaires were handed out to 646 outpatients who because of underlying diseases should be vaccinated annually against influenza. Questions concerned whether a patient was vaccinated, and if the vaccine had not been administrated, what the reason was. Answered questionnaires were received from 595 patients (92%). In the particular year 333 patients (56%) had received the vaccine. The majority of the immunized patients had received personal advice from their physician to have the vaccine. Lack of advice, the belief that vaccination is unnecessary, and fear of side effects were the most important reasons for not having the vaccine. We conclude that personal advice from the patients' physician, sending annual reminders to patients and offering the vaccine to patients in an easily accessible way, are the essential elements for a successful vaccination strategy. PMID- 1736131 TI - [Exogenous ochronosis, a little-known side effect of hydroquinone-containing ointments]. AB - Two patients with exogenous ochronosis, an unfamiliar side effect of hydroquinone containing bleaching creams, are presented. This disorder is characterized by progressive darkening of the area to which the cream is applied. Histologically there is deposition of yellow-brown pigment in the dermis, in addition to degeneration of collagen and elastic fibres. The chemical composition of the ochronotic material and the pathogenesis of this paradoxical effect of hydroquinone are unknown. Hydroquinone containing creams should not be used for longer than two years. If there is no improvement within six months, application should be discontinued. PMID- 1736132 TI - [Sulfonylurea preparations and hypoglycemia]. PMID- 1736133 TI - [EDTA-chelation treatment]. PMID- 1736134 TI - [Antiseptic wound treatment agents; an overview]. PMID- 1736135 TI - [Anticoagulants in non-rheumatic atrial fibrillation]. PMID- 1736136 TI - [Clinical findings and diagnosis of Yersinia enterocolitica infections; a retrospective study in Friesland]. PMID- 1736137 TI - [The surgical treatment of rheumatoid arthritis]. PMID- 1736138 TI - [Surgical treatment of ischemic ventricular septum rupture]. PMID- 1736139 TI - [Promotion of neurological recovery using drugs following acute traumatic spinal cord lesions]. PMID- 1736140 TI - [Treatment of psoriasis using dithranol]. PMID- 1736141 TI - [Gonadotrophins and induction of (super)ovulation]. PMID- 1736142 TI - [Neck lymph node dissection in squamous cell carcinoma originating in the head and-neck area; the significance for the prognosis]. AB - Neck dissection has a therapeutical as well as a prognostic relevance with respect to regional recurrence and distant metastases. Between January 1973 and July 1986 576 neck dissections in 511 patients (396 men, 115 women, among whom 486 with squamous cell carcinoma of the head and neck, and 14 with neck metastases of an unknown primary tumour) were performed at the department of Otolaryngology-Head and Neck Surgery of the Free University Hospital, Amsterdam. Patients with tumour at the margins were excluded. Recurrence-free curves were calculated according to Kaplan-Meier and the log rank test was used to test the differences. All patients underwent a comprehensive neck dissection and were irradiated postoperatively when three or more tumour-positive nodes or extranodal spread were reported by the pathologist. Endpoint for analysis was occurrence of an ipsilateral neck recurrence or of a distant metastasis. Figures were corrected for a simultaneous recurrence at a higher level. A total of 29 neck recurrences (7.2%; n = 523) and 26 distant metastases (10.7%; n = 281) were demonstrated in the 5-year follow-up period. The number of positive nodes was of prognostic significance for both events (p = 0.039 and p = 0.0027). Extranodal spread was shown only to increase the incidence of distant metastases (p = 0.017), whereas its prognostic value with regard to recurrence in the neck was nullified by the strict institution of postoperative radiotherapy. It is recommended to give radiotherapy to patients with two positive nodes and possibly to every patient with a histopathologically positive neck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736143 TI - [Prognostic factors for the survival time in gallbladder carcinoma]. AB - Survival of 74 patients with proven gallbladder carcinoma was studied retrospectively. Initial treatment consisted of cholecystectomy, cholecystectomy and common bile duct exploration, bypass procedure (hepatojejunostomy) or laparotomy and biopsy or percutaneous biliary drainage. Staging (according to the American Joint Committee on Cancer) was the most important determinant for survival (chi 2 = 29.34; df 3; p less than 0.001). Most individual complaints such as pain (chi 2 = 1.66;), nausea/vomiting (chi 2 = 0.35), and palpable mass (chi 2 = 2.62) were not related significantly with survival. However cachexia (chi 2 = 17.12; df I; p less than 0.001) was correlated with decreased survival. Establishing the diagnosis preoperatively was associated with significantly shorter survival (chi 2 = 22.67; df I; p less than 0.001) than establishment at the moment of hospitalisation. In a hospital where a radical surgical treatment is not performed, less invasive non surgical therapy (insertion of an endoprosthesis) could probably be considered for this group of patients. Selected patients should be referred to a centre for a radical surgical approach. PMID- 1736144 TI - [Function-oriented budgeting and budget-oriented functioning]. PMID- 1736145 TI - [Dilemmas in the diagnosis and treatment of spinal epidural metastases]. PMID- 1736146 TI - [Dilemmas in the diagnosis and treatment of spinal epidural metastases]. PMID- 1736147 TI - [Echography in the 1st pregnancy trimester is prognostically valuable]. PMID- 1736148 TI - [Echography in the 1st pregnancy trimester is prognostically valuable]. PMID- 1736149 TI - [Conform breathing sounds]. PMID- 1736150 TI - [Transient ischemic attacks, non-invalidating brain infarcts and the prevention of worse: current findings on treatment]. PMID- 1736151 TI - [30 mg acetylsalicylic acid per day is equally effective as 238 mg in patients following a transient ischemic attack or a non-invalidating brain infarct, and with fewer side effects]. PMID- 1736152 TI - Assessment: techniques associated with the diagnosis and management of sleep disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. AB - Polysomnography and measurements of physiologic sleepiness (MSLT/MWT) have been established as effective and safe in identifying many sleep/wake disorders, and have identified and defined a number of specific conditions such as SDB, narcolepsy, idiopathic CNS hypersomnia, periodic movements of sleep, and the REM sleep behavior disorder. The performance of these studies requires specialized equipment and accommodations. This technology, coupled with other clinical information and appropriate medical tests, particularly in experienced hands, is valuable in the diagnosis, classification, and treatment of patients with sleep disorders. PMID- 1736153 TI - The unexpected benefit of stealth. PMID- 1736154 TI - Imagery mnemonics and memory remediation. AB - This paper evaluates the claim that imagery mnemonic techniques are useful in remediation of memory disorders in brain-damaged patients. Clinical research has confirmed that such techniques can lead to improved performance on formal testing in a number of neurologic disease populations and following lesions of either the left or right hemisphere. However, those patients with more severe forms of amnesia and those with medial or bilateral damage do not improve unless the learning task is highly structured. Even among patients who show improvement on formal testing, there is little evidence that they maintain the use of these techniques in similar learning tasks or generalize the use to new learning situations. Imagery mnemonics also appear to be of little practical value in the daily activities that are of most concern to brain-damaged patients themselves. The effectiveness of imagery mnemonics appears to depend upon the patients' motivation and insight rather than upon their intelligence or educational level. Instead of training patients in specific mnemonic techniques, clinicians should promote the development of "meta-cognitive" skills and the acquisition of knowledge about domains of practical significance. PMID- 1736155 TI - Alzheimer's disease transmission: possible artifact due to intercurrent illness. PMID- 1736156 TI - Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. AB - We evaluated the influence of time of recanalization or degree of initial leptomeningeal collateral blood flow in cardioembolic or arterio-arterial middle cerebral artery (MCA) occlusion on infarct size and clinical outcome in a series of 34 consecutive acute stroke patients with main stem (N = 31) or major branch (N = 3) occlusions using CT, initial cerebral arteriography (N = 21), repetitive close-meshed transcranial Doppler ultrasonography, and a neurologic stroke scale. We treated 15 patients with tissue plasminogen activator intravenously within the first 6 hours. The type and size of infarction depended on the location of the occluding lesions within the MCA trunk. Proximal MCA occlusion always led to infarction involving the striatum and internal capsule. Sixty-five percent of patients showed recanalization of the occluded MCA within 1 week. Following MCA recanalization, hyperperfusion was present in 38 to 44% of cases. There was a marginally significant relation between size of infarction on CT and recanalization time within the first 24 hours. The more rapidly recanalization occurred, the smaller the size of the infarct. When recanalization time was greater than 8 hours, the lesions always extended to the cortex. An additional good leptomeningeal collateral blood flow significantly reduced the size of the infarct and improved clinical outcome after 17 days and after 10 months. Early recanalization of embolic MCA occlusions within up to 8 hours, in conjunction with good transcortical collateralization, has a favorable impact on infarct size and outcome and may constitute the therapeutic window of opportunity. PMID- 1736157 TI - Infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank: neurologic examination. AB - To gain insight into neurologic signs relevant to the diagnosis of cardiogenic embolism, we analyzed data from 1,290 patients with cerebral infarcts in the NINDS Stroke Data Bank. Based solely on the presence of potential cardiac sources of embolism, we divided patients into groups of high (N = 250), medium (N = 167), and low (N = 873) risk of a cardiogenic mechanism for their stroke. Diminished level of consciousness was highly associated with the presence of a cardiac source of embolism. Of the four primarily cortical deficits assessed, three (visual field abnormalities, neglect, and aphasia) showed a highly significant graded relationship to the cardiac risk groups. For the fourth cortical deficit (other nonlanguage cognitive functions), this relationship did not attain statistical significance. Conversely, hemiparesis without sensory or cortical deficits had a strong inverse association to the presence of a cardiac source of embolism. This inverse association was weaker for sensorimotor strokes and nonexistent for pure sensory strokes. Although some neurologic findings had highly significant associations with the presence of a cardiac source of embolism, their predictive value for an embolic source was low. PMID- 1736158 TI - Fatal familial insomnia: clinical and pathologic study of five new cases. AB - In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined. PMID- 1736159 TI - Diminished curiosity in patients with probable Alzheimer's disease as measured by exploratory eye movements. AB - Clinical accounts of Alzheimer's disease (AD) suggest that some patients exhibit markedly diminished curiosity and initiative early in the course of their illness. Such behavioral changes are extremely difficult to measure experimentally. We studied one aspect of curiosity by measuring exploratory eye movements in response to provocative visual stimuli in 12 patients with probable AD and 10 matched controls. Subjects viewed slides, each of which contained an incongruous or irregular figure paired with a congruous or regular one. Unlike controls, who spent significantly more time viewing the incongruous stimuli, AD patients distributed their viewing time equally and spent significantly less time than controls looking at the novel stimuli. Additionally, when presented with picture slides containing an unexpected element, AD patients exhibited diminished visual exploration overall and decreased attention to the incongruous part. Further analyses suggest that the results cannot be adequately explained by a general decline in cognition or by problems with ocular motility or directing visual attention. We conclude that AD patients exhibit diminished curiosity which can be measured by the study of exploratory eye movements. PMID- 1736160 TI - Interrater reliability in the neuropathologic diagnosis of Alzheimer's disease. AB - Three neuropathologists evaluated brain sections from 43 aged subjects for the presence of Alzheimer's disease. Moderate-to-substantial agreement was obtained. After discussion of disparate diagnoses, agreement was almost perfect for standardized and substantial for personal criteria. We conclude that reproducibility can be improved if diagnoses based on standardized criteria are discussed by at least two neuropathologists. PMID- 1736161 TI - Motor blocks in Parkinson's disease. AB - Freezing episodes and related phenomena (as a general term, motor blocks [MBs]) are poorly understood, particularly disabling, and a therapeutically frustrating problem in Parkinson's disease (PD). Epidemiologic and clinical characteristics of MBs, as well as risk factors to develop MBs, have never been fully addressed. Herein, we report our database survey on 990 PD patients, of whom 318 (32%) had MBs. The majority of MBs were linked to gait. Start hesitation occurred in 86%, blocking on turning in 45%, and blocking in narrow spaces in 25% of patients. Initial parkinsonian symptoms in the upper body and tremor as the initial motor symptom were less likely to be associated with the presence of MBs (odds ratios [OR] 0.6 and 0.7, respectively), while initial symptoms affecting gait or trunk had higher association with MBs (OR = 1.58). Longer disease duration, higher Hoehn and Yahr stage, and longer duration of levodopa treatment are all significantly associated with the presence of MBs. We observed significant association between the existence of MBs and levodopa-induced dyskinesias to suggest similar pathophysiology. We propose that MBs in PD are abnormal retrieval or execution of complex motor tasks that can occur as a result of disease progression or as short- or long-term side effects of levodopa treatment. PMID- 1736162 TI - Selegiline as initial treatment in de novo parkinsonian patients. AB - To investigate the efficacy and safety of selegiline in the early phase of Parkinson's disease (PD), we carried out a placebo-controlled, double-blind, parallel trial. De novo PD patients were randomized to receive either selegiline (10 mg/d) or matching placebo. We continued selegiline or placebo until levodopa therapy became necessary and assessed the disability using three different rating scales at baseline, after 3 weeks, at 2, 4, 8, and 12 months, and at every 4 months thereafter. Fifty-two patients were eligible for the analysis, 27 in the selegiline group and 25 in the placebo group. The median duration of time before levodopa had to be initiated was 545 +/- 90 days with selegiline and 372 +/- 28 days with placebo (p = 0.03). Disability was significantly less in the selegiline group than in the placebo group up to 12 months. The period of time during which the mean total Columbia University Rating Scale score stayed below the baseline was used to express the initial symptomatic effect of the treatments. The difference in this initial improvement time between the two groups was about 3 months and did not alone explain the difference in the delay of the need to start levodopa therapy. Selegiline was well tolerated and there were no severe side effects. We conclude that selegiline delays the need to start levodopa in de novo PD patients, has symptomatic efficacy, and possibly retards the progression of the disease. PMID- 1736163 TI - Autosomal dominant spinocerebellar ataxia: locus heterogeneity in a Nebraska kindred. AB - SCA1 is an adult-onset autosomal dominant ataxia that is genetically linked to loci on chromosome 6p. A highly informative GT-repeat marker, D6S89, has been closely linked to the SCA1 locus in five large kindreds. We have used this marker to perform linkage analysis in a smaller autosomal dominant ataxia family consisting of five generations designated as the Nebraska kindred. This kindred includes 33 affected (12 living) and 40 first-generation at-risk individuals. We examined eight affected individuals; all had gait and limb ataxia. We analyzed the D6S89 locus by the polymerase chain reaction. Based on the analysis of 31 individuals from this kindred, we statistically excluded linkage to D6S89 for moderate-to-tight linkage (less than 11% recombination). These data clearly demonstrate genetic heterogeneity among the autosomal dominant ataxias. In addition, we obtained linkage data for HLA-A and SCA1 in this kindred. Comparison of HLA-A with D6S89 shows the latter marker to be more powerful. Use of D6S89 and other highly polymorphic markers in this region will greatly facilitate genetic classification of ataxias and make presymptomatic diagnosis of SCA1 feasible. PMID- 1736164 TI - Immunosuppression promotes CNS remyelination in chronic virus-induced demyelinating disease. AB - Immunosuppression using cyclophosphamide or anti-T cell monoclonal antibodies (mAbs) directed at CD4 or CD8 promoted remyelination of CNS axons in the spinal cords of mice infected chronically with Theiler's virus. Treatment with a mAb directed at class II major histocompatibility gene products did not increase the extent of CNS remyelination. Following immunosuppressive treatment, quantitative morphometry revealed a five- to sevenfold increase in new myelin synthesis. Proliferating nervous system cells were identified at the edges of remyelinated lesions by their incorporation of [3H]thymidine. CNS remyelination occurred in mice depleted of selected subsets of T lymphocytes despite the local persistence of viral antigen. These findings indicate that CNS remyelination occurs as a normal consequence of primary myelin injury, but factors associated with immune T cells somehow impair remyelination. Interference with the function of immune T cells enhances CNS remyelination by oligodendrocytes. Similar depletion of immune T cells may allow for enhanced remyelination in the CNS of patients with chronic multiple sclerosis. PMID- 1736165 TI - Elevated CSF beta-endorphin immunoreactivity in Rett's syndrome: report of 158 cases and comparison with leukemic children. AB - Because some symptoms of Rett's syndrome are suggestive of excessive endogenous opioid activity, we measured the levels of beta-endorphin-like immunoreactivity in lumbar CSF from 158 affected female patients and from 13 female controls. The mean (+/- SE) control level of beta-endorphin immunoreactivity in CSF was 35.3 +/ 2.8 pg/ml (range, 23 to 48 pg/ml), whereas those with Rett's syndrome had a mean level of 95.3 +/- 3.6 pg/ml (range, 31 to 293 pg/ml). The levels of beta endorphin immunoreactivity in initial CSF samples exceeded the control range in 90% of the patients with Rett's syndrome. The mean beta-endorphin immunoreactivity was also elevated in CSF from leukemic children (119.2 +/- 16.9 pg/ml; range, 40 to 159 pg/ml), relative to the control group. These results are consistent with the hypothesis that some symptoms of Rett's syndrome may be associated with excessive endogenous opioid levels in the CNS. PMID- 1736166 TI - The expression of a cerebellar degeneration-associated neural antigen in human tumor line cells. AB - We examined the expression of the paraneoplastic cerebellar degeneration associated autoantigen (PCD-AA) protein in human tumor lines of different origins by using an immunoaffinity-purified antibody from a patient with paraneoplastic cerebellar degeneration (PCD) and uterine adenocarcinoma. Immunocytochemical studies revealed that this antigen is expressed in the cytoplasm of two different uterine carcinoma lines and the tumor lines of neural origin as well as in the cytoplasm of a normal skin fibroblast line. By immunoblot analysis, we detected a 52-kd antigen identical to the PCD-AA protein in all the cell lines studied, including a colon adenocarcinoma line, a small-cell lung carcinoma line, and a squamous cell lung carcinoma line. These results indicate that the PCD-AA protein is expressed in a wide range of tumor cells. In this respect, this antigen is distinguishable from the cerebellar degeneration-related--34 antigen, of which expression is confined to tumor lines of neuroectodermal origin and not detected in colon, breast, or ovarian carcinoma lines derived from patients without PCD. These findings suggest the variability of the immune response to antigens in PCD. PMID- 1736167 TI - Very-late-onset adrenoleukodystrophy: possible precipitation of demyelination by cerebral contusion. AB - We report the clinical history, neuroradiology, and autopsy findings in a patient with very late onset, at age 57, of adrenoleukodystrophy (ALD) presenting with dementia, hemianopia, and gait apraxia. Open brain biopsy, elevated plasma very long-chain fatty acids, and autopsy confirmed the diagnosis of ALD. Demyelinative lesions were most extensive at the site of a recent cerebral contusion. CNS trauma may have precipitated or accelerated demyelination in this patient carrying the ALD gene. PMID- 1736168 TI - Dystonia, clinical lateralization, and regional blood flow changes in temporal lobe seizures. AB - We analyzed the lateralizing value of ictal dystonia and head-turning in temporal lobe epilepsy, and sought the biologic basis of these clinical signs by studying the regional changes in perfusion with ictal single-photon emission computed tomography (SPECT). We identified unilateral temporal lobe epilepsy in 40 of 42 patients undergoing evaluation for temporal lobe surgery, and with ictal SPECT all 40 showed striking hyperperfusion of the epileptogenic temporal lobe. Twenty five of the 40 patients showed unilateral or predominantly unilateral upper limb dystonia, which was opposite the epileptic temporal lobe in all cases. Analysis of regional count ratios in cases with ictal dystonia, compared with those without, showed significant changes only in the basal ganglia. Specifically, we found that ictal dystonia was associated with a relative increase in perfusion of the basal ganglia opposite the dystonic limb. Although we found 26 cases with head-turning, the sign was of no lateralizing value, even when only those with major or "tonic" versions (n = 11) were analyzed. Slight increases in cortical blood flow on the side opposite the direction of version were associated with head-turning, irrespective of the side of seizure focus. In clinical practice, ictal SPECT is a highly accurate aid in the lateralization of temporal lobe foci, in addition to providing a new method to investigate the pathophysiology of clinical signs in focal seizures. PMID- 1736169 TI - Magnetic resonance demonstration of intracranial CSF flow in children. AB - We determined the feasibility and value of studying intracranial CSF flow in children with potential CSF pathway problems using a cardiac gated cine magnetic resonance (MR) format. We studied 15 consecutive patients with a variety of clinical problems that suggested possible CSF pathway problems. The diagnoses included Chiari malformation, Dandy-Walker syndrome, external hydrocephalus, cerebellar tumor, CNS histoplasmosis, and tuberculous meningitis. In addition to documenting the feasibility of the technique in children (7 of 15 were less than 2 years of age), we derived significant new information relative to pathogenesis and/or therapy. The study provides preliminary evidence supporting intracranial CSF flow studies at the time of routine MR imaging of appropriate children. PMID- 1736170 TI - Nicotine-sensitive paresis. AB - Immediately after a patient with myoclonus epilepsy smoked a nicotine-containing cigarette, tetraparesis and hyperreflexia with ankle clonus developed, but disappeared within several minutes. During paresis, the H-reflex size of the soleus muscle increased, EEG showed more slow waves than before smoking, and the cerebral perfusion increased around the motor cortex as shown by single photon emission CT. A similar effect occurred when the patient chewed nicotine gum, and smoking a cigarette with a high nicotine content induced severe positive and negative myoclonus after the development of tetraparesis. Administration of the C6-type nicotinic antagonist mecamylamine not only countered the smoking effect, but ameliorated the spontaneous positive and negative myoclonus. Mecamylamine may prove useful for the treatment of positive and negative myoclonus in myoclonus epilepsy. PMID- 1736171 TI - Epilepsy due to neurocysticercosis: analysis of 203 patients. AB - We reviewed clinical, EEG, and CT findings of 203 patients with epilepsy due to neurocysticercosis. Seizures were generalized in 121 patients and partial in 82. Thirty-two patients had focal signs and eight had papilledema. Eighty-one had generalized and 16 had focal EEG abnormalities. CT showed parenchymal brain calcifications in 53 patients and cysts in 150. There was an increased rate of focal signs in patients with single cysts as compared with patients with multiple cysts, and focal EEG abnormalities were present only in patients with single cysts. Fifty patients were lost to follow-up. The remaining 153 patients were followed for 28 +/- 6 months; of these, 31 had calcifications and 122 had cysts. Anticonvulsants were started after the first visit in every patient. The 31 patients with calcifications remained free of seizures. Ninety-five of the 122 patients with cysts were also treated with anticysticercal drugs; of these, 79 (83%) had control of seizures. In contrast, only seven (26%) of 27 patients who did not receive anticysticercal drugs had control of seizures, indicating a strong correlation between the use of anticysticercal drugs and seizure control. Finally, of the 21 patients in whom anticonvulsants were withdrawn, 16 had relapses. PMID- 1736172 TI - Migraine, suicidal ideation, and suicide attempts. AB - We examined the risk of suicide attempts and suicidal ideation separately in persons with (1) migraine with aura alone, (2) migraine with aura and coexisting major depression, (3) migraine without aura alone, and (4) migraine without aura and coexisting major depression. Persons with migraine with aura alone and migraine with aura and coexisting major depression had significantly higher rates of suicide attempts and suicidal ideation compared with persons with neither migraine nor major depression. The rates of suicide attempts and suicidal ideation in persons with migraine with aura and major depression were higher than the combined rates in persons with major depression alone and migraine with aura alone. In contrast, migraine without aura was not associated with an increased risk for suicide attempts and suicidal ideation. PMID- 1736173 TI - Memory function in normal aging. AB - We evaluated memory function in a group of 161 community-dwelling, cognitively normal individuals aged 62 to 100 years recruited as part of the Mayo Clinic Alzheimer's Disease Patient Registry. We used the Free and Cued Selective Reminding Test and the Rey Auditory Verbal Learning Test to evaluate two aspects of memory function thought to be sensitive to the effects of aging: learning (acquisition) and delayed recall (forgetting). The results were quite consistent and demonstrated that learning or acquisition performance declines uniformly with increasing age but is not related to education. Delayed recall or forgetting, however, remained relatively stable across age when adjusted for the amount of material initially learned. These findings are relevant for assessing normal memory function relative to the early impairments found in dementia and form a baseline against which memory performance can be assessed by the clinician. In particular, suspicion regarding a disorder of brain function affecting memory processes should be raised if learning performance declines more rapidly than expected or if delayed recall is impaired to any significant extent. PMID- 1736174 TI - Tremor in MPTP-induced parkinsonism. AB - We assessed clinical and electrophysiologic characteristics of tremor in patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Four of seven patients with moderate to severe MPTP-induced parkinsonism exhibited a tremor indistinguishable from the characteristic rest tremor of Parkinson's disease (PD). The pathology induced by MPTP in one human case is confined to the substantia nigra, but in nonhuman primates, the locus ceruleus or the ventral tegmental area can also be affected. These findings suggest that the pathophysiology of rest tremor in PD might result from damage to either the substantia nigra alone or in combination with damage to one or more of these other regions. PMID- 1736175 TI - Dopamine-receptor autoradiography of human narcoleptic brain. AB - Although the pathology of human narcolepsy is unknown, studies of human and canine narcolepsy have suggested that dopamine metabolism may be disturbed. We used quantitative autoradiography to assess dopamine D1- and D2-receptor binding in basal ganglia and amygdala of five narcoleptic and 17 control human brains. In caudate, narcoleptic brains had a statistically significant increase of 57% in D1 receptor binding, and large but not significant increases of 54% in medial globus pallidus D1 binding, 63% in caudate D2-receptor binding, 95% in lateral globus pallidus D2 binding, and 93% in lateral amygdala D2 binding. We found no major changes in the putamen or in the basal or accessory basal nuclei of the amygdala. These results suggest that narcolepsy is associated with upregulation of dopamine receptors in specific areas of the brain, although medications used prior to death may have contributed to the findings. PMID- 1736176 TI - A noninvasive protocol for anterior temporal lobectomy. AB - We report the results of a protocol for choosing candidates for temporal lobectomy using a standard battery of objective tests without intracranial electrodes. We assigned each test a level of importance, and an algorithm was used to determine whether temporal lobectomy could be performed. Fifty-one patients (total pool, 103 patients) met protocol requirements and had an anterior temporal lobectomy with a mean follow-up of 39.4 months (range, 21 to 64 months), most remaining on anticonvulsant therapy. Eighty percent are seizure free, 12% have less than 3 seizures per year or only nocturnal seizures, and 8% have greater than 80% reduction in seizure frequency. One-third of patients who failed protocol criteria did not have temporal lobe seizures when studied with intracranial electrodes. We analyzed and modified the algorithm after comparing these patients with others who were poor candidates for temporal lobectomy. We conclude that this protocol is effective and recommend using such an objective algorithm. PMID- 1736177 TI - Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. AB - An American family of English origin with an unusually early onset and long duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression. PMID- 1736178 TI - Cognitive functioning in cancer patients: effect of previous treatment. AB - Neuropsychological analysis of 47 cancer patients with widely metastatic disease and significant previous treatment indicated that 34% had cognitive deficits. Previous treatment with biologic response modifiers was associated with a 53% frequency of cognitive abnormalities, whereas only 18% of patients who were never treated with biologics had such impairments. The possibility that neurobehavioral abnormalities will result from metastatic disease and treatment regimens is an important factor in determining the risks and benefits of therapy. PMID- 1736180 TI - Coma with triphasic wave pattern in EEG as a complication of temporal arteritis. AB - Coma is rare in temporal arteritis (TA). We describe a patient with TA who suddenly developed coma with a triphasic EEG pattern that resolved after initiation of steroid treatment. Although the arterial lesions in TA are segmental in nature, TA may present with signs of diffuse neurologic deficit; early treatment can result in complete resolution. PMID- 1736179 TI - Toxoplasmosis with early intracerebral hemorrhage in a patient with the acquired immunodeficiency syndrome. AB - Cerebral hemorrhage is a rare complication of the acquired immunodeficiency syndrome. We report a case of multifocal hemorrhage in a 37-year-old homosexual man with cerebral toxoplasmosis. Histopathologic examination, performed at cerebral autopsy, confirmed the findings on CT and MRI. PMID- 1736181 TI - Longitudinal study of essential tremor. AB - We measured wrist tremor and forearm EMG in 18 patients with essential tremor on two occasions separated by periods of 4 to 8 years. The frequency of tremor decreased 0.28 Hz to 3.21 Hz in 10 patients and changed less than 0.25 Hz in the remaining eight patients. Thus, the frequency of essential tremor may decrease over time. PMID- 1736182 TI - Periodic triphasic waves in levodopa-induced encephalopathy. AB - Four patients with idiopathic Parkinson's disease developed subacute confusional states, associated with delusions, hallucinations, and myoclonus, following an increase in the dose of levodopa. The EEG revealed periodic generalized triphasic waves. The clinical condition and EEG cleared following levodopa dose reduction or discontinuation. This is the first report of encephalopathy associated with periodic triphasic activity following levodopa treatment. PMID- 1736183 TI - Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. AB - Postmortem analyses of Alzheimer's disease (AD) brain tissue reveal reactive microglia expressing high levels of major histocompatibility complex (MHC) glycoproteins, immunoglobulin receptors, and complement receptors; small but significant numbers of T-lymphocytes infiltrating tissue; enhanced cytokine and cytokine receptor expression; and profuse immunoreactivity for complement proteins of the classic pathway colocalized with senile plaques, dystrophic neurites, and some neurofibrillary tangles. Protectin, clusterin, and vitronectin, three proteins designed to defend host cells against "bystander lysis" caused by the membrane attack complex of complement, are all expressed at high levels in AD tissue but not in normal tissue. Taken together, these findings indicate that immune-mediated autodestructive processes may occur in AD. In view of the urgency to find treatments for AD and disappointing results with the many classes of pharmacologic agents that have so far been given clinical trials, exploration of the effectiveness of anti-inflammatory agents may now be warranted. PMID- 1736184 TI - The history of the blink reflex. PMID- 1736185 TI - Robert Boyle and a corpuscular model of tremor. PMID- 1736186 TI - Paralysis of fourth cranial nerve due to superior-cerebellar artery aneurysm. PMID- 1736187 TI - Acute ventricular dilatation in adult meningococcal meningitis. PMID- 1736188 TI - Acute encephalopathy associated with the eosinophilia-myalgia syndrome. PMID- 1736189 TI - Creutzfeldt-Jakob disease in a pathologist. PMID- 1736190 TI - MS and syringomyelia. PMID- 1736191 TI - Hemorrhagic infarction. PMID- 1736192 TI - Nurses must change society ... PMID- 1736193 TI - Reference list dated. PMID- 1736194 TI - Structure decision-making & authority systems. PMID- 1736195 TI - Cost, standards, quality and technology. PMID- 1736197 TI - The art of "breaking set". PMID- 1736196 TI - Why executive information systems are important. PMID- 1736198 TI - Implications of RBRVS fees for RNs. PMID- 1736199 TI - Legislation introduces equal pay for nonphysician providers. PMID- 1736200 TI - A model for costing and pricing nursing service. PMID- 1736201 TI - Budget variance analysis and justification. PMID- 1736202 TI - Budget response to volume variability. PMID- 1736203 TI - Pediatric payors and providers. PMID- 1736204 TI - Director of nursing planning and finance: a new role. PMID- 1736205 TI - Psychiatric mental health nursing specialist process evaluation criteria. PMID- 1736206 TI - Goal-directed temporal plans of care. PMID- 1736207 TI - Evaluating readiness of recent graduates. PMID- 1736208 TI - Health issues: from rhetoric to reform. PMID- 1736209 TI - Costing two streamlined nursing procedures. PMID- 1736210 TI - Northern California's innovative recruitment efforts. PMID- 1736211 TI - Franciscan Children's Hospital goes wireless. PMID- 1736212 TI - CD-ROMs: libraries at your fingertips. PMID- 1736213 TI - Choosing a staffing agency. PMID- 1736214 TI - Befrienders: hospital volunteers at work. PMID- 1736215 TI - Education: learning the pitfalls of codependency. PMID- 1736216 TI - Disposables v. reusables in OR practice: Part I, Weighing contributions to patient care. PMID- 1736217 TI - Dentistry comes of age. PMID- 1736218 TI - Increasing knowledge of AIDS/HIV infection through continuing education. AB - A survey of dentists found significant differences among groups with varying amounts of continuing education with respect to knowledge about AIDS. These findings suggest focused continuing education may be beneficial. PMID- 1736219 TI - The incredible odontogenic keratocyst. AB - The aggressive behavior and high recurrence rate of the odontogenic keratocyst make it unique among odontogenic cysts. Successful treatment requires meticulous evaluation and diagnosis, proper surgical management and continued follow up. PMID- 1736220 TI - The sophisticated dental practitioner. General principles influencing diet, nutrition and human behavior. PMID- 1736221 TI - AIDS and the dental profession. PMID- 1736222 TI - Organized dentistry benefits young dentists too. PMID- 1736223 TI - And a Happy New Year. PMID- 1736224 TI - The other side of the story. PMID- 1736225 TI - Credit where due. PMID- 1736226 TI - Sterile surroundings. PMID- 1736227 TI - [The era of molecular genetics. New perspectives in hematology]. AB - The unprecedently swift developments in molecular genetics opened up a new era in haematology. The regulation of the expression of globin genes and its coordination with the expression of genes coding for other red cell specific proteins, as well as molecular genetics of some intrinsic haemolytic anaemias and the clinically important recent results revealing the genetic regulation of iron metabolism are discussed. New unfolding concepts of the physiological regulation of the haemopoetic stem cell and the multistep development of its malignant transformation are reported. The unlimited possibilities rendered by the rDNA technology in diagnostics and therapy of haematological diseases is pointed out. The present state of art of gene therapy including the first trials with gene transplantation in humans is discussed. PMID- 1736228 TI - [Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)]. AB - Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis. PMID- 1736229 TI - [Experience with ciprofloxacin therapy of salmonellosis gastroenteritica]. AB - Five days' ciprofloxacin treatment resulted quick clinical improvement in all of the 45 patients with salmonella gastroenteritis and stool cultures of 35 patients became negative. The advantages of ciprofloxacin treatment are analysed in comparison with previous antibiotics. Indications for new quinolones in the treatment of salmonella gastroenteritis are summarized. It is emphasized that antibiotic therapy is unnecessary in mild cases of salmonella gastroenteritis. This is demonstrated on the basis of case reports of 12 patients with symptomatic treatment too. PMID- 1736230 TI - [Relationship between weight increase during pregnancy and weight of the newborn]. AB - The data of first 1000 first-born, non-malformed, mature (greater than or equal to 2500 g) offspring of participants in the Hungarian "Optimal" Family Planning Programme were evaluated. The mean maternal weight gain during pregnancy was 13 kg which was modified by the body weight of women. Maternal weight gain exceeded 13 kg in 54% of pregnant women. There was an obvious positive correlation between maternal weight gain and birth weight which was calculated as 26.6 g/kg. PMID- 1736231 TI - [Prinzmetal angina pectoris causing diagnostic and therapeutic problems]. AB - A 53 year old patient was hospitalized because of retrosternal oppression which was unrelated to effort and recurred in the early morning hours. An esophageal diverticulum and a hiatal hernia were found. The patient had complaints in spite of medical therapy and an operation was performed because of his oesophageal disorders. After operation the patient had the same pain. A cardiologist was asked, who suggested Prinzmetal variant angina. During arteriography coronary artery disease was found. Coronary bypass surgery was indicated and performed, after that procedure the patient was and remained free of any complaints. This observation reaffirmed Prinzmetal original statement "The key to the diagnosis ... is the taking of a painstaking history". PMID- 1736232 TI - [In memoriam Antal Rozsas]. PMID- 1736233 TI - [Bone marrow transplantation and its status in Hungary]. PMID- 1736234 TI - [Pathomechanism of tetany reaction]. PMID- 1736235 TI - [Surrogate motherhood or nursing-mother pregnancy]. PMID- 1736236 TI - [Follow up studies on patients with Buerger's disease treated with omentum transplantation]. PMID- 1736237 TI - [Results of cholesterol screening in Budapest]. PMID- 1736238 TI - [Possibilities of preventing alopecia after cytostatic therapy]. PMID- 1736239 TI - [The non-ulcer dyspepsia syndrome]. PMID- 1736240 TI - Pathology annual: nineteen ninety-two. Part I. PMID- 1736241 TI - Adrenal cortical neoplasms in the pediatric and adolescent age group. Clinicopathologic study of 30 cases with emphasis on epidemiological and prognostic factors. PMID- 1736242 TI - Transmucosal needle aspiration biopsy via the fiberoptic bronchoscope. Value and limitations in the cytodiagnosis of tumors and tumor-like lesions of the lung. PMID- 1736243 TI - A pathologist's perspective on the sudden infant death syndrome--1991. PMID- 1736244 TI - Invasive lobular carcinoma of the breast. The importance of an alveolar growth pattern. PMID- 1736245 TI - What is intestinal neuronal dysplasia? PMID- 1736246 TI - Oncocytes, oncocytosis, and oncocytic tumors. PMID- 1736247 TI - Ploidy analysis and cerebrospinal fluid nephelometry as measures of clinical outcome in childhood choroid plexus neoplasia. PMID- 1736248 TI - Solitary rectal ulcer syndrome. Mucosal prolapse syndrome. PMID- 1736249 TI - Histological criteria for the diagnosis of reflux esophagitis. PMID- 1736250 TI - The organization and delivery of clinical genetics services. AB - Advances in genetics, including mapping the human genome, improved therapy for genetic disorders, recognition of the role of genetic factors in common diseases of adulthood, and new screening tests for carrier detection and presymptomatic diagnosis create an increased demand for and awareness of clinical genetic services. These services, focusing on diagnosis, management, and genetic counseling, had been supported by a variety of state, provincial, federal, and foundation grants. As clinical genetics has evolved from a service with roots in research provided solely at academic medical centers to one widely available in the community, the services in the United States are increasingly provided on a fee-for-service basis in various settings including private hospitals, state supported outreach clinics, and free-standing genetics centers, whereas in Canada they are generally based in university hospital settings and are covered by universal health care. Given the limited numbers of clinical geneticists and genetic counselors now practicing, much of the application in this decade of new genetic technologies and knowledge will fall upon primary care physicians. PMID- 1736251 TI - Medical genetics I. PMID- 1736252 TI - Teratology in pediatric practice. AB - A range of infections, physical agents, maternal diseases and metabolic states, drugs, and chemicals have been demonstrated to be human teratogens. These agents cause structural or functional disabilities postnatally in exposed embryos and fetuses. Such disabilities are potentially totally preventable through public education and awareness. Pediatricians must be able to recognize potential teratogenic exposures, diagnose teratogenically-induced disabilities, and be knowledgeable in the natural history of these disorders so that they can support and educate those who care for these children in the home and in the community. PMID- 1736253 TI - Support groups for patients with genetic disorders and their families. AB - In conclusion, those working in pediatric clinics owe it to themselves to know about the relatively new team member, the genetic support group. As the human genome becomes less mysterious to professional and patient alike and as its demystification creates an ever-increasing number of ethical and social dilemmas, consumers and professionals, interested perhaps for different reasons in finding treatment and cure, must work together as partners. Availability of medical care for the family who must cope with a genetic disorder is only one part of the total health picture. Access to communication with and compassion of one family with another family, of one child with another child, of one parent with another parent, within a support group of caring persons, proves one of the most meaningful medical tools that pediatricians can offer their patients. Those working within the walls of the pediatric clinic are in a crucial place to address the comprehensive needs of families with genetic disorders and to identify the role of the genetic support group in a treatment plan. PMID- 1736254 TI - Dysmorphologic diagnosis for the pediatric practitioner. AB - Attaining an accurate diagnosis in children with congenital abnormalities is an important and sometimes vital part of their care. With a basic knowledge of the types and causes of birth defects, the pediatric clinician often can arrive at a correct diagnosis, even in children with rare syndromes or multiple anomalies. This article reviews the four major mechanisms that produce congenital defects, discusses the various types and subtypes of structural anomalies, and provides an algorithmic approach to their diagnosis. PMID- 1736255 TI - Pregnancy loss, stillbirth, and neonatal death. A guide for the pediatrician. AB - The complete clinical evaluation of pregnancy loss, stillborn infants, and neonatal deaths can result in the anticipation of an accurate diagnosis in a high percentage of cases. Appropriate focused fetal studies may include a clinical examination, fetal karyotype, photographs, skeletal radiographs, fetal autopsy, examination of the placenta and cord, and occasionally cultures or DNA studies. Knowledge of specific causes of fetal death and their clinical presentation can greatly assist the pediatrician in choosing the most appropriate studies. Many of the disorders leading to fetal death carry significant genetic recurrence risks, making an accurate diagnosis even more crucial. As our understanding of the causes of pregnancy loss improves, so does our ability to provide families with accurate counseling regarding their reproductive options. PMID- 1736256 TI - Ethnocultural approaches to genetics. AB - Human cultural needs are not easily categorized, studied, or taught to others outside the group. Generalizations about groups are made to increase the awareness of differences and commonalities. It is hoped that this increased sensitivity will serve as a catalyst for the individual to develop a greater awareness of the importance of culture in delivery of genetic services. PMID- 1736257 TI - Registries of birth defects and genetic diseases. AB - Registries can be very useful scorecards for tracking the occurrence of birth defects and genetic diseases and for monitoring the effectiveness of prevention programs. They can also help us to identify causes and risk factors and develop new prevention approaches. For registries to be useful, however, their data must be precise and focus on time, place, person, and diagnosis. PMID- 1736258 TI - Ethical issues in genetics. AB - Clinical genetics encompasses all ethical issues in medicine and health care. Geneticists, like all health care practitioners, regularly encounter problems of truth telling, paternalism, confidentiality, and rationing. The facts and circumstances under which familial ethical questions arise differ among specialties, but the underlying ethical questions cut across disciplines. The purpose of this article is to provide a review of the ethical issues that commonly arise in the clinical practice of genetics. Accordingly, the goal is primarily to identify common positions and justifications for various approaches as well as to identify consensus where they seem to exist. PMID- 1736259 TI - Genetic diagnosis based on molecular analysis. AB - This article presents the significant advances made in the area of applied molecular genetics in recent years. DNA analysis is now possible for a large number of single gene disorders. The type of testing available for those disorders most commonly dealt with by pediatricians is briefly outlined. Rapid advancement is expected to continue as new techniques are developed and mutations detected. This in turn will lead to extending DNA applications from the family with an affected child to using DNA for population screening of certain disorders. PMID- 1736260 TI - Prognosis in fetal tetralogy of Fallot. AB - The outcome in a series of 23 cases of tetralogy of Fallot diagnosed prenatally was compared to published figures for this condition when (a) identified postnatally or (b) treated surgically. There was a marked difference in the survival between these groups, with the highest mortality (75%) occurring when the diagnosis had been made prenatally. The high incidence of chromosomal and extracardiac anomalies in this group (60%) largely accounted for the discrepancy. This, and the potential for progressive changes in the anatomy of the defect during pregnancy, must be taken into account by the pediatric cardiologist offering prognosis in early pregnancy. PMID- 1736261 TI - Countercurrent aortography: an alternative to cardiac catheterization in infancy. AB - Countercurrent aortography via a peripheral artery was used to clarify the aortic arch anatomy in 25 infants in whom cross-sectional and Doppler evaluation was inconclusive. Ages ranged from 3 days to 11 months (median 9 days), and 80% were neonates. The suspected diagnosis was aortic coarctation in 21 infants, interrupted aortic arch in two, recoarctation in one, and vascular ring in one. A countercurrent aortogram provided adequate diagnostic information in 24 infants. A diagnosis of coarctation was confirmed in 15, interruption of the aortic arch in two, and vascular ring in one. In six infants countercurrent aortography excluded the presence of anomalies of the aortic arch. In only one infant, who had an anomalous origin of the right subclavian artery from the descending aorta, did this technique fail to provide adequate information. The only complication observed was transient ischemia of the arm in one patient. Countercurrent aortography is a minimally invasive procedure that can provide adequate angiographic information without the need for cardiac catheterization in patients with inconclusive echocardiographic evaluation. Injection into a right upper limb artery is preferred, because it gives better opacification of the ascending and transverse aortic arch than injection into a left one. PMID- 1736262 TI - Central venous catheterization in infants and children with congenital heart diseases: experiences with 500 consecutive catheter placements. AB - In a prospective study results of central venous catheter (CVC) placements in a consecutive group of 500 patients with less than 20 kg body weight undergoing cardiac surgery were evaluated. The incidence of previous cardiac surgery was 21% and the incidence of factors preventing the primary puncture of the right jugular or innominate vein was 13.4%. The anesthesiologists were free to select the catheterization technique, site of puncture, and catheter type. All CVC insertions were performed prior to surgery under continuous circulatory monitoring and optimal positioning of the anesthetized patient. Ninety-six percent of all catheterizations were successful, 81% of them on the first attempt. In the 4% of cases where catheterization failed, a CVC had to be placed by the surgeon. Of all catheters, 66% were positioned via the right internal jugular (IJV) or innominate vein (IV), 8% via the left, 16% via an external jugular vein (EJV), and 5% via other veins. Seventy-six percent of CVC insertions were performed with the Seldinger technique. Of the four catheter types used in this study, double lumen catheters were most frequently selected (38%). Placement of 22-ga single lumen catheters was preferred in infants with less than 5 kg body weight, in spite of their tendency to kink. Observed complications (10% arterial puncture, 4% hematoma, and 1% intrathoracic bleeding) never required immediate surgical intervention. Careful selection of appropriate catheters, as well as extensive experience and knowledge of the anatomical structures involved in special heart defects, helped to keep the risk of complications low. PMID- 1736263 TI - Echocardiographic evaluation of the aortic root and mitral valve in children and adolescents with isolated pectus excavatum: comparison with Marfan patients. AB - Pectus excavatum, mitral valve prolapse (MVP), and dilated aortic root occur frequently in patients with Marfan's syndrome (MS). Patients with isolated pectus excavatum (IPE) have a high prevalence of MVP, but it is not known whether aortic root dilatation is a risk in those patients. To test the hypothesis that IPE and MS represent a spectrum of connective tissue dystrophy with MV and aortic root involvement, two-dimensional (2D) echocardiography was used to measure the aortic root diameter and assess for MVP in IPE (n = 31), MS (n = 14), and normal (n = 16) gender- and age-matched patients. Aortic root was measured in parasternal long- and short-axis views, just above the aortic sinuses, at end systole, in six cardiac cycles, and averaged. Parasternal long-axis view was used to assess for MVP. Aortic root diameter in IPE patients was not different from that in normal subjects, 24 +/- 4 mm vs 22 +/- 4 mm (p = NS), respectively, both were significantly smaller than that in MS patients (30 +/- 5 mm; p less than 0.05). MVP was present in 17 of 31 (55%) IPE patients vs 12 of 14 (86%) MS patients (p = NS) and in only 1 of 16 (6%) normal subjects (p less than 0.05) vs both IPE and MS. We conclude that young patients with IPE represent an isolated form of connective tissue abnormality because of the presence of pectus excavatum and MVP, but this is different from the systemic involvement of MS because of the lack of other systemic findings, including aortic root dilatation and changes in body habitus. PMID- 1736264 TI - Imperforate tricuspid valve with dysplasia of the right ventricular myocardium, pulmonary valve, and coronary artery: a clinicopathological study of nine cases. AB - Nine cases of imperforate tricuspid valve associated with dysplasia of the right ventricular myocardium, pulmonary valve, and right coronary artery are described. The mean frontal QRS axis of the electrocardiograms did not indicate left axis deviation in seven of the nine. Two-dimensional echocardiograms showed an imperforate tricuspid valve, normally aligned atrioventricular septum, and an irregular-shaped right ventricular cavity with a thin wall. In three cases with absence of the pulmonary valve, pulsed Doppler echocardiograms of the right ventricular outflow tract revealed antegrade flow during systole and retrograde flow during diastole, and selective angiography through a persistent ductus arteriosus showed retrograde filling of the blind-ended right ventricular cavity via the main pulmonary artery. Necropsy examinations showed an imperforate tricuspid valve with a thin-walled aneurysmal right ventricle in all six cases examined. Pulmonary atresia was observed in two cases, and the absence of the pulmonary valve in four. The right coronary artery was hypoplastic in four cases and absent in two. A shunt operation should be carried out in early infancy to prevent hypoxia after closure of the ductus arteriosus. PMID- 1736265 TI - Hemodynamic effects of peritoneal dialysis in three children following open heart surgery. AB - We studied the hemodynamic responses of peritoneal dialysis (PD) in three children following open heart surgery. Hemodynamic measurements were made prior to a dialysis run, following the instillation of dialysis solution (20 ml/kg), and immediately prior to and 5 min after drainage of the peritoneal cavity. The same protocol was repeated 48 h later. There was a significant increase in right atrial pressure (RAP) and mean pulmonary artery pressure upon instillation of the dialysate into the peritoneal cavity (p less than 0.01). However, cardiac index, mean arterial blood pressure (MAP), systemic (SVRI) and pulmonary vascular resistances (PVRI), left atrial pressure (LAP), and oxygen saturation did not change significantly. There were no significant differences between responses in the initial study and that performed 48 h later. PD is associated with modest right-sided hemodynamic changes which, in this small group of patients, did not compromise patient care. PMID- 1736266 TI - Acquired coarctation of the aorta. AB - Coarctation of the aorta is usually caused by a congenital narrowing of the aorta. This report describes two children who developed hypertension secondary to an acquired coarctation of the aorta. In one patient the coarctation was temporally related to umbilical artery catheterization and was associated with thrombosis and aneurysmal dilatation of the aorta. In the second patient, the coarctation occurred after surgical aortotomy during the removal of an intrathoracic neuroblastoma. Patients who have interventional damage to the aorta should be periodically examined for the appearance of a coarctation. Although an acquired coarctation of the aorta is an infrequent complication of invasive or surgical procedures, it should be identified since it represents a remediable cause of hypertension in children. PMID- 1736267 TI - Catheter embolization of pulmonary arteriovenous fistulas in an infant. AB - An infant with pulmonary arteriovenous fistulas is described. Surgical ligation of the fistulas and limited resection of parenchyma from the right lung was followed at 11 months of age, by successful steel coil embolization of residual fistulas. PMID- 1736268 TI - Sick sinus syndrome and diffuse impairment of the conduction system in a child: successful pacing with a steroid eluting endocardial pacing lead. AB - A 9-year-old patient who had had a syncope was found to have atrial flutter in a resting electrocardiogram (ECG). Brief phases of sinus arrest had previously occurred after drug conversion to sinus rhythm. Structural heart disease was excluded by cardiac catheterization and angiography. Electrophysiologic study revealed a sick sinus syndrome, associated with diffuse impairment of the conduction system (supra-, infra-, and intrahisian block). Epimyocardial and an endocardial pacemaker implantation failed because of high stimulation threshold, after 3 years and 2 weeks, respectively. At the third implantation a steroid eluting endocardial pacing lead was used and satisfactory pacing was still present 2 years later. PMID- 1736269 TI - Chloramphenicol toxicity associated with severe cardiac dysfunction. AB - A 9-month-old infant experienced severe chloramphenicol toxicity associated with high serum levels (313 micrograms/ml). Cardiovascular collapse with cardiomyopathic changes and impaired left ventricular function was documented by echocardiography. Serial echocardiographic evaluation showed resolution of the cardiomyopathic findings as the chloramphenicol levels were spontaneously cleared. Clinical course was complicated by the development of liver disease and coagulopathy compatible with disseminated intravascular consumption. Patient's recovery was complete and uneventful, nevertheless, chloramphenicol toxicity in childhood is associated with a significant mortality rate of 40%. The related impaired cardiac function, although reversible, appears to play a major role in the pathogenesis and eventual outcome in this syndrome. PMID- 1736270 TI - Left ventricular function and myocardial mass after aortic valvotomy in infancy. AB - Eighteen of 25 survivors of aortic valvotomy in infancy were reinvestigated by cross-sectional echocardiography a mean of 7.5 (2.3-13.4) years after surgery. They had been operated at a median age of 38 (5-330) days. At the follow-up examination the gradient across the aortic valve was 41 +/- 19 (15-85) mmHg and the ejection fraction was 0.73 +/- 0.10 (0.48-0.84). Left ventricular (LV) end diastolic volume was 66 +/- 17 (33-191) ml/m2. LV mass was 96 +/- 36 (44-204) g/m2 and the LV mass volume index (LVMVI) (mass divided by end-diastolic volume) was 1.43 +/- 0.4 (0.9-2.28). Eleven of 18 patients had an abnormally high mass volume index compared with 95 age-matched controls with structurally normal hearts. The correlation between the residual pressure gradient across the aortic valve and mass volume index yielded an r value of 0.75 (p less than 0.0004). One patient had been reoperated and underwent resection of a subaortic stenosis 4 years after the initial operation. Four patients with a resting gradient of more than 50 mmHg and one with grade 4 aortic regurgitation are scheduled for further surgical treatment. We conclude that, although LV function was normal in most patients who underwent aortic valvotomy in infancy, LV mass remains elevated in a significant number of patients, who may remain at risk of developing subendocardial ischemia. PMID- 1736271 TI - Infantile cardiac hemangioendothelioma. AB - A 4-month-old infant with cardiac hemangioendothelioma presented with thrombocytopenia, and pericardial effusion, as well as signs and symptoms of heart failure. This is the first reported case of infantile cardiac hemangioma successfully treated with steroids. PMID- 1736272 TI - Gaucher's disease with mitral and aortic involvement: echocardiographic findings. AB - Cardiac involvement in Gaucher's disease has been reported in only a few patients, mostly adults with pericardial changes. We describe findings in two siblings with Gaucher's disease, aged 15 and 9 years respectively, in whom mitral and aortic valve lesions were evaluated by auscultation and echocardiography. In both cases the mitral and aortic valves were thick and restricted in motion. Continuous Doppler echocardiography revealed significant mitral regurgitation and mitral stenosis. At the aortic valve level there was a systolic pressure gradient. Echocardiographic investigation of patients with suspected cardiac involvement with Gaucher's disease is recommended. PMID- 1736273 TI - Right ventricular outflow obstruction by anomalies of the tricuspid valve: report of a windsock diverticulum. AB - A 9-month-old infant with a clinical diagnosis of double outlet from the right ventricle, subaortic ventricular septal defect, and muscular subpulmonary obstruction underwent surgical repair. The defect was corrected and the right ventricular infundibulum enlarged with a patch. Eight hours after the operation there was a sudden collapse which rapidly progressed to cardiac arrest and death. Postmortem examination of the heart confirmed the clinical diagnosis but noted that the subpulmonary obstruction was caused by a "windsock" deformity of the tricuspid valve which was not identified at operation. The variants of malformations of the tricuspid valve causing subpulmonary obstruction are reviewed. PMID- 1736274 TI - Transient ventricular septal hypertrophy in the first year of life associated with neonatal brain injury. PMID- 1736275 TI - Density dependent polarized secretion of a prostatic epithelial cell line. AB - The polarized secretions (apical/basal) of newly synthesized total protein and proteases from prostatic epithelial sheets of PA-III cells grown in dual compartment chambers were investigated at various cell densities and culture conditions. PA-III cells grown in a serum free defined medium (SFDM) form morphologically polarized monolayers of epithelial cells. These cells secreted their 35S-methionine labeled total protein in a predominantly apical direction (apical/basal ratio, 4-8 fold), with a lesser proportion of protein secreted apically at lower cell densities of the PA-III cell monolayer. PA-III cells grown in 5% fetal calf serum (FCS) are morphologically squamous, comparable to the anaplastic phenotype, and exhibited an inversion of polarized total protein secretion (apical/basal ratio, 0.4-0.9 fold), with an increased proportion of total protein secreted in a basal direction at lower cell densities. Since the culture of PA-III cells in FCS may approximate the anaplastic phenotype we investigated the polarized secretion of proteases from these cells at various cell densities, and compared them with the secretory pattern of protease secretion from polarized PA-III cells cultured in SFDM. At lower cell densities of the PA-III cells grown in FCS the polarity of protease secretion was inverted such that metalloproteinases, tissue type plasminogen activator, and a 72 kD gelatinase were secreted in a predominantly basal direction, as well as urokinase and a gelatinase of 26 kD that were secreted more or less equally into the apical and basal compartments of the chambers. On the other hand, for cultures of PA-III cells grown in SFDM the aforementioned proteases exhibited predominantly an apically directed polarity of secretion. These results suggest that the anaplastic phenotype characterized by a loss of polarized structure may also be characterized by a functional loss or inversion of polarized secretion. The consequences of such a loss or inversion of polarized secretion would be to increase the localized concentrations of proteases along the basal domain of cells thereby facilitating degradation of the basement membrane and interstitial tissue in vivo. PMID- 1736276 TI - Evidence for a non-estrogenic cytostatic effect of estramustine on human prostatic carcinoma cells in vivo. AB - Estramustine is one of the main metabolites of estramustine phosphate (EstracytR), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400 micrograms daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of 3H-estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (EstradurinR). This is the first time evidence has been presented demonstrating the anti-mitotic effect of estramustine in vivo. PMID- 1736277 TI - A local direct effect of pituitary graft on growth of the lateral prostate in rats. AB - Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats. PMID- 1736278 TI - Distribution of estradiol-17 beta hydroxysteroid oxidoreductase in the urogenital tract of control and neonatally estrogenized male mice: immunohistochemical, enzymehistochemical, and biochemical study. AB - The present study was conducted to investigate the regional distribution of the enzymes catalyzing the interconversion of the hydroxyl and carbonyl groups at C 17 of the estrogen molecule within the male urogenital tract of adult mouse and to test the hypothesis, whether regional differences in the distribution are critical for estrogen responses. The highest ratios of NADPH-dependent 3H estrogen reduction to oxidation at C-17 of cell-free homogenates were obtained from coagulating gland and seminal vesicle as well as from the prostatic and lower intrapelvic urethra, which are considered the most estrogen-sensitive parts of the male urogenital tract. Both NADP- and NAD-dependent oxidation of 3H-17 beta-estradiol were low or nondetectable at these sites. The epithelium of the lower and prostatic urethra as well as the periurethral collecting ducts were stained with the antibody prepared against human placental 17 beta-hydroxysteroid oxidoreductase. The NAD-dependent 3H-estradiol-17 beta oxidase activity was highest in the bladder epithelium, and the activity declined sharply in the urinary tract from the bladder downward. The lowest detectable activities were found in vas deferens and prostate (combined ventral and dorsolateral lobes). The uneven distribution of estradiol-17 beta oxidase activity may provide additional explanation for the regional differences of estrogen responses. The NADPH dependent 17 beta-reduction of estrone and the immunohistochemical staining of the human placental estradiol-17 beta oxidoreductase antigenicity were not significantly altered after neonatal estrogenization. These findings do not lend any support to the idea that the increased estrogen sensitivity observed after neonatal estrogenization is associated with changes in 17 beta-oxidoreduction. However, the possibility remains that there are specific sites (e.g., epithelium of prostatic urethra and collecting ducts) in which the changes in 17 beta oxidoreduction of estrogen does play a role in the regulation of estrogen action. PMID- 1736279 TI - Distribution of lactoferrin in the normal and inflamed human prostate: an immunohistochemical study. AB - A polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation-related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate-specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post-inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post-inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin-positive. Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate. PMID- 1736280 TI - Ha-ras oncogene activation in mammary glands of N-methyl-N-nitrosourea-treated rats genetically resistant to mammary adenocarcinogenesis. AB - A single dose of N-methyl-N-nitrosourea given to sexually immature female Buf/N rats produces a high incidence of mammary adenocarcinomas. A large percentage of these tumors contain the Ha-ras oncogene, activated by a G----A transition at the second nucleotide of codon 12. Copenhagen rats, on the other hand, are completely resistant to mammary tumor induction by a number of carcinogens, including N methyl-N-nitrosourea. Here we show, using a sensitive method involving PCR, that codon 12 Ha-ras mutations occur in the mammary glands of both Buf/N and Copenhagen rats 30 days after N-methyl-N-nitrosourea treatment. These mutations were evenly distributed among individual mammary glands and were present in purified mammary epithelial cells. In Buf/N rats, the fraction of cells containing a mutated Ha-ras allele increased by a factor of 10-100 between 30 and 60 days, whereas in Copenhagen rats, there was no such increase during this time period. We conclude that the resistance of the Copenhagen rat to mammary carcinogenesis is not due to a defect in initiation but rather appears to be due to the inability of cells containing a mutated ras allele to undergo sustained clonal expansion. PMID- 1736281 TI - Transactivation of the proenkephalin gene promoter by the Tax1 protein of human T cell lymphotropic virus type I. AB - Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax1, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. We have investigated the effect of Tax1 on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5' deletion mutants of the promoter region showed that sequences upstream of base pair -190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax1-mediated transactivation of the proenkephalin promoter. Neither Tax1 transactivation alone nor Tax1/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax1-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax1 transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases. PMID- 1736282 TI - In vivo duplication of genetic elements by the formation of stem-loop DNA without an RNA intermediate. AB - Gene duplication through cDNA synthesis by reverse transcriptase is believed to have played an important role in the diversification of genomes during evolution. Here, we demonstrate that a genomic DNA sequence can be duplicated in vivo as a result of template switching. When an inverted repeat (IR) structure was inserted in a site downstream from a ColE1 plasmid origin of DNA replication, transformation of Escherichia coli cells with this plasmid resulted in the production of a new DNA fragment encompassing the region from the origin to the center of the IR structure. The structure of this DNA molecule is composed of a long stem-loop formed by a single-stranded DNA, in which the loop is formed by the IR structure. The DNA fragment is designated slDNA, for stem-loop DNA. The experiments in this study suggest that during DNA replication, template switching at the stem-loop structure formed by the IR structure gives rise to slDNA utilizing the nascent DNA strand or the parental strand as a template. The mechanistic implications of slDNA synthesis, and its possible roles in genome evolution, are discussed. PMID- 1736283 TI - Effects of different DNA polymerases in ligation-mediated PCR: enhanced genomic sequencing and in vivo footprinting. AB - We have developed a simplified procedure for the ligation-mediated polymerase chain reaction (LMPCR) using Thermococcus litoralis DNA polymerase (Vent DNA polymerase). We show that Vent DNA polymerase produces correct, blunt-ended primer extension products with substantially higher efficiency than Thermus aquaticus (Taq) DNA polymerase or modified T7 DNA polymerase (Sequenase). This difference leads to significantly improved genomic sequencing, methylation analysis, and in vivo footprinting with LMPCR. These improvements include representation of all bands with more uniform intensity, clear visualization of previously difficult regions of sequence, and reduction in the occurrence of spurious bands. It also simplifies the use of DNase I cut DNA for LMPCR footprinting. PMID- 1736284 TI - Ectopic lymphokine gene expression in human peripheral blood lymphocytes in vivo. AB - An animal model to study the effects of ectopic expression of cytokines involved in cell growth and differentiation has been established. Retrovirus vectors containing the human interleukin 6 cDNA were used to produce high titer virus producing lines. Human peripheral blood lymphocytes (hPBLs) were successfully infected with the retrovirus and engrafted into severe combined immunodeficient mice. The majority of the animals were engrafted with hPBLs, as determined by the presence of human glucose phosphate isomerase. Furthermore, six of seven mice engrafted with hPBLs infected with high titer virus and detectable hPBLs present in the spleen expressed the retroviral human interleukin 6 gene. Importantly, human interleukin 6 protein was expressed at physiologically significant levels in these mice. These results demonstrate that models for human disease and immunotherapy involving retrovirus-mediated gene transfer into human cells can be developed in mice. PMID- 1736285 TI - Structural basis for the nucleic acid binding cooperativity of bacteriophage T4 gene 32 protein: the (Lys/Arg)3(Ser/Thr)2 (LAST) motif. AB - To identify the functional residues of the N-terminal B region of bacteriophage T4 gene 32 protein involved in its cooperative binding to single-stranded nucleic acids, a process dependent on homotypic protein-protein interaction, we have studied the interaction of the protein with synthetic peptides containing different portions of this domain. Gel-permeation chromatography showed that a 6 acryloyl-2-dimethylaminonaphthalene (acrylodan)-labeled fluorescent peptide corresponding to the first 17 residues of gene 32 protein formed a complex with whole protein. The fluorescence was blue-shifted 14 nm upon interaction with intact protein, and somewhat less so (7-11 nm) with cleavage products of the protein lacking B domains. The intrinsic tryptophan fluorescence of whole and truncated protein was quenched by this peptide and by the nonderivatized peptide. The peptide bound tightly to truncated protein at both 0.015 and 0.44 M Na+, with a stoichiometry of 1:1. Similar tryptophan quenching or acrylodan blue shifts were obtained with peptides corresponding to residues 1-9 and 3-8, but not residues 1-4, 5-9, or 5-17, indicating that the essential amino acids are contained within positions 3-8, Lys-Arg-Lys-Ser-Thr-Ala. Several other DNA binding proteins contain a LAST motif with documented involvement of these residues in nucleic acid interaction. The amino acid and coding sequence of residues 110-114, a region proposed to be involved in nucleic acid binding, is virtually identical to that of residues 3-7. Based on these observations, we have formulated a model for the cooperative interactions of gene 32 protein with single-stranded nucleic acids. PMID- 1736286 TI - Transcription factor TFIID induces DNA bending upon binding to the TATA element. AB - The TATA box-binding factor TFIID plays a primary role in the process of transcription initiation by RNA polymerase II and its regulation by various gene specific factors. Here we employ a permuted binding site/gel retardation assay with recombinant yeast and human TFIID to show that this factor induces DNA bending around the TATA element. These results are consistent with the presence of G + C-rich sequence elements flanking the consensus TATA element and led to the recently confirmed suggestion that TFIID interacts with the TATA element via the minor groove. They also raise the possibility that TFIID-induced bending might facilitate promoter interactions of other general factors in the preinitiation complex or interactions between general transcription factors and regulatory factors bound at upstream sites. PMID- 1736287 TI - Reduced expression of AP27 protein, the product of a growth factor-repressible gene, is associated with diminished adipocyte differentiation. AB - We have recently characterized an adipocyte cDNA (clone 5) that is enhanced in expression by environmental and hormonal conditions favoring adipogenic differentiation. Moreover, certain agents including fibroblast growth factor and phorbol 12-myristate 13-acetate (but not epidermal growth factor) markedly inhibit clone 5 gene expression and prevent TA1 cell differentiation. These results led us to propose that a threshold level of the clone 5 gene product (AP27 protein) is required for triggering adipocyte differentiation. We have constructed vectors that direct the synthesis of clone 5 antisense RNA to reduce the levels of AP27 in adipogenic cell lines TA1 and 3T3-L1. We show here that when these cells express clone 5 antisense RNA, they fail to undergo morphological differentiation, whereas adipogenesis is unaffected in cells expressing antisense beta-actin or ferritin heavy-chain RNA. We further show that cells expressing clone 5 antisense RNA (but not the other antisense RNAs) are unable to induce the expression of characteristic "adipocyte-specific" mRNAs. The level of inhibition of differentiation by clone 5 antisense RNA correlates with decreased levels of AP27 protein. These results provide strong evidence that expression of AP27 is linked to adipogenic differentiation and that AP27 may be a component of an as-yet-uncharacterized signal-transduction pathway required for the triggering of adipocyte differentiation. PMID- 1736288 TI - Regulation of glycine tRNA gene expression in the posterior silk glands of the silkworm Bombyx mori. AB - The glycine tRNA genes in silkworm Bombyx mori contain two regulatory regions upstream of the transcription start site as identified by direct transcription of 5' deletion mutants, transcription competition, gel mobility shift assays, and footprinting. A positive regulatory region is present in the immediate 5' flanking sequences of the four tRNA 1Gly clones studied. This region is essential for cell-free transcription in homologous extracts. A negative regulatory region is present farther upstream, and transcription competition experiments indicate its presence in three of the four clones examined. PMID- 1736289 TI - Duplication-targeted DNA methylation and mutagenesis in the evolution of eukaryotic chromosomes. AB - Mammalian genomes are threatened with gene inactivation and chromosomal scrambling by recombination between repeated sequences such as mobile genetic elements and pseudogenes. We present and test a model for a defensive strategy based on the methylation and subsequent mutation of CpG dinucleotides in those DNA duplications that create uninterrupted homologous sequences longer than about 0.3 kilobases. The model helps to explain both the diversity of CpG frequencies in different genes and the persistence of gene fragmentation into exons and introns. PMID- 1736290 TI - Distribution of interspersed repeats (Alu and Kpn) on NotI restriction fragments of human chromosome 21. AB - Interspersed repeated sequences (Alu and Kpn) were used as probes to detect a set of Not I restriction fragments of human chromosome 21 from the hybrid cell line WAV17. Forty different Not I fragments, ranging in size from less than 0.05 megabase (Mb) to 7.0 Mb, were identified. The total length of these fragments was 47.3 Mb. This length provides an estimate of the minimum size of the chromosome and a minimum number of fragments to be ordered to create a complete restriction map. The average length Not I fragment is 1.2 Mb. Alu and Kpn fragments are not always coincident: a 2.9-Mb fragment is detected with Kpn but not with Alu, and 13 fragments, ranging from less than 0.05 Mb to 5.6 Mb, are detected with Alu but not with Kpn; the 26 remaining fragments, covering 75% (35.3 Mb) of the total length, are detected with both repetitive probes. The presence of so many noncoincident fragments and the high variation of the hybridization signal intensities of the fragments suggest a very nonuniform distribution of Kpn and Alu repeats. PMID- 1736291 TI - Tamoxifen prevents induction of hepatic neoplasia by zeranol, an estrogenic food contaminant. AB - Zeranol (alpha-zearalanol) is a beta-resorcylic acid lactone (RAL) that has estrogen activity. It is synthesized by molds and is difficult to avoid in human food products. We tested the ability of this mycoestrogen to damage the liver of the Armenian hamster, a rodent that is especially sensitive to hepatotoxic effects of exogenous estrogens. Zeranol induced acute hepatotoxicity and, subsequently, hepatic carcinogenesis; both effects were blocked by tamoxifen, suggesting estrogen receptor mediation. Because zeranol is acting alone as a primary initiator of hepatic neoplasms, this model provides an unusual opportunity to study the pathogenesis of estrogen-initiated tumorigenesis. PMID- 1736292 TI - A relationship between the helical twist of DNA and the ordered positioning of nucleosomes in all eukaryotic cells. AB - A large number of measurements of nucleosome repeat lengths are analyzed and are found to exhibit preferential quantization to a set of values related by integral multiples of the helical twist of DNA. This implies that the nucleosomal DNA content is preferentially quantized, which in turn implies that linker DNA lengths are preferentially quantized. This study confirms and extends previous observations in the literature that had suggested, but not firmly established, that linker lengths might be quantized. The quantization of repeat lengths applies even for very long repeat lengths. This suggests a model for the origin of the quantization, in which the quantization arises from the requirements of higher-order chromatin structure. PMID- 1736293 TI - Intron-exon organization of the gene for the multifunctional animal fatty acid synthase. AB - The complete intron-exon organization of the gene encoding a multifunctional mammalian fatty acid synthase has been elucidated, and specific exons have been assigned to coding sequences for the component domains of the protein. The rat gene is interrupted by 42 introns and the sequences bordering the splice-site junctions universally follow the GT/AG rule. However, of the 41 introns that interrupt the coding region of the gene, 23 split the reading frame in phase I, 14 split the reading frame in phase 0, and only 4 split the reading frame in phase II. Remarkably, 46% of the introns interrupt codons for glycine. With only one exception, boundaries between the constituent enzymes of the multifunctional polypeptide coincide with the location of introns in the gene. The significance of the predominance of phase I introns, the almost uniformly short length of the 42 introns and the overall small size of the gene, is discussed in relation to the evolution of multifunctional proteins. PMID- 1736294 TI - Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. AB - Glucose is the main fuel for energy metabolism in the normal human brain. It is generally assumed that glucose transport into the brain is not rate-limiting for metabolism. Since brain glucose concentrations cannot be determined directly by radiotracer techniques, we used 13C NMR spectroscopy after infusing enriched D-[1 13C]glucose to measure brain glucose concentrations at euglycemia and at hyperglycemia (range, 4.5-12.1 mM) in six healthy children (13-16 years old). Brain glucose concentrations averaged 1.0 +/- 0.1 mumol/ml at euglycemia (4.7 +/- 0.3 mM plasma) and 1.8-2.7 mumol/ml at hyperglycemia (7.3-12.1 mM plasma). Michaelis-Menten parameters of transport were calculated to be Kt = 6.2 +/- 1.7 mM and Tmax = 1.2 +/- 0.1 mumol/g.min from the relationship between plasma and brain glucose concentrations. The brain glucose concentrations and transport constants are consistent with transport not being rate-limiting for resting brain metabolism at plasma levels greater than 3 mM. PMID- 1736295 TI - Profound specific suppression by antigen of persistent IgM, IgG, and IgE antibody production. AB - Ongoing, high-titer T-cell-dependent immune responses in adult mice, consisting of IgM, IgG, and IgE anti-fluorescein antibodies, can be specifically and substantially reduced (90-99%) when the mice are injected with appropriate doses of fluoresceinated dextran of defined molecular weight and hapten valence. This suppressive form of the antigen is nontoxic and specific, as responses to other antigens are unaffected. The suppression is long lasting and reduces high affinity antibodies most markedly. Moreover, plasma cell secretion of specific antibody is virtually eliminated. This demonstrates that the reduction in antibody titer is not simply due to masking of serum antibody by the suppressive polymer. The results are discussed with reference to proposed models of B-cell and T-cell tolerance. Extension of these findings to disease-related immunogens may yield effective antigen-specific treatments of human allergy and autoimmune diseases. PMID- 1736296 TI - Isolation of a src homology 2-containing tyrosine phosphatase. AB - Tyrosine phosphorylation is controlled by the opposing actions of tyrosine kinases and phosphotyrosine phosphatases (PTPs). src homology 2 domains (SH2) are found in several types of signaling proteins, including some tyrosine kinases. These domains bind phosphotyrosyl proteins and thus help promote signal transduction. Using mixed oligonucleotide-directed polymerase chain reactions, two previously undescribed rat PTP cDNA fragments were generated. Through subsequent screening of rat megakaryocyte and human erythroleukemia libraries, we obtained a full-length coding sequence for one of these fragments. This cDNA, SH PTP1, encodes a tyrosine phosphatase containing two highly conserved SH2 domains. SH-PTP1, with a 2.4-kilobase mRNA, a predicted open reading frame of 595 amino acids, and a structure suggesting a nontransmembrane protein, is expressed primarily in hematopoietic and epithelial cells. When expressed in Escherichia coli, SH-PTP1 possesses PTP activity. The structure of SH-PTP1 establishes an additional branch of the tyrosine phosphatase family and suggests mechanisms through which tyrosine phosphatases might participate in signal transduction pathways. PMID- 1736297 TI - Long-term expression of human adenosine deaminase in vascular smooth muscle cells of rats: a model for gene therapy. AB - Gene transfer into vascular smooth muscle cells in animals was examined by using recombinant retroviral vectors containing an Escherichia coli beta-galactosidase gene or a human adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) gene. Direct gene transfer by infusion of virus into rat carotid arteries was not observed. However, gene transfer by infection of smooth muscle cells in culture and seeding of the transduced cells onto arteries that had been denuded of endothelial cells was successful. Potentially therapeutic levels of human adenosine deaminase activity were detected over 6 months of observation, indicating the utility of vascular smooth muscle cells for gene therapy in humans. PMID- 1736298 TI - Mechanism of DNase I hypersensitive site formation within the human globin locus control region. AB - The human beta-like globin gene locus contains embryonic, fetal, and adult globin genes that are regulated in a developmentally timed, as well as a tissue specific, manner. The locus control region (LCR), located 5' of the globin genes, is characterized by four erythroid-specific nuclease-hypersensitive sites within native chromatin. These sites contain the active elements of the LCR. The LCR establishes an active chromatin conformation across the globin locus and enhances globin gene expression in transfected erythroleukemia cells and transgenic mice. We have used 5' DNase I hypersensitive site (HS) 4 as a model to define the minimum elements necessary for site formation. We have identified a 101-base-pair fragment within 5' HS4 that is the active site-forming element. DNase I footprint and gel-mobility shift assays have identified binding sites for transcription factors AP-1/NF-E2, Sp-1, and GATA-1 within the HS-forming element. We conclude that HS formation, the characteristic feature of the LCR in nuclear chromatin, requires interaction between erythroid-specific and ubiquitous nuclear proteins. PMID- 1736299 TI - Amino acid sequence of the mRNA cap-binding protein from human tissues. PMID- 1736300 TI - Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes. PMID- 1736301 TI - Materials derived from biomass/biodegradable materials. AB - Interest in biodegradable plastics made from renewable resources has increased significantly in recent years. PHBV (polyhydroxybutyrate-polyhydroxyvalerate) copolymers are good examples of this type of materials. This paper provides an overview of the manufacturing process, properties, biodegradability, and application/commercial issues associated with PHBV copolymers. They are naturally produced by bacteria from agricultural raw materials, and they can be processed to make a variety of useful products, where their biodegradability and naturalness are quite beneficial. PHBV copolymers are still in the first stage of commercialization. But they are presented in this paper as an example of how new technology can help meet society's needs for plastics and a clean environment. PMID- 1736302 TI - A new approach to evaluating carcinogenic risk. AB - Carcinogenic risk assessments are based on extrapolating from high-dose chronic rodent-feeding studies to human-exposure levels. A serious problem is that about half of all substances tested at their respective maximum tolerated dose (MTD) are found to induce cancer. The MTD as currently defined has been criticized because it may stimulate cell proliferation in susceptible tissues. Such chemically induced mitogenesis is postulated to increase the probability that neoplasia will develop at the affected site. It is proposed that, in the development of an MTD for a given substance, chemically induced mitogenesis be considered an undesirable toxic manifestation. Hence, mitogenesis should not be induced by a substance fed at its true MTD. Since MTDs determined in this fashion are likely to be lower than those developed using current criteria, an added level of protection is introduced by employing a safety factor similar to that used now in determining acceptable daily intakes for noncarcinogenic food additives. In calculating acceptable daily intakes, the usual safety factor is 100; i.e., the acceptable daily intake is set at 1% of the no-observed-effect level. Hence it is proposed that the acceptable daily level of exposure to a substance that does not induce cancer at its MTD as defined herein be set at 1% of that MTD. On the other hand, a chemical that induces cancer at its MTD as defined herein would continue to be regulated as is customary now. PMID- 1736303 TI - Identification of a negative regulatory element involved in tissue-specific expression of mouse renin genes. AB - The 5' flanking region of the mouse renin genes (Ren-1d and Ren-2d) contains two motifs that are homologous to known negative regulatory elements (NREs). Ren-2d has a 150-base-pair (bp) insertion 5' to the upstream putative NRE (NRE-1), which is lacking in Ren-1d. We tested the functionality of these sequences by using site-directed mutagenesis to delete individually each putative NRE from Ren-1d and to delete the 150-bp insertion from Ren-2d. We examined the effect of these mutations on the expression of the reporter gene chloramphenicol acetyltransferase, which was expressed from a truncated thymidine kinase promoter fused to the renin regulatory region. This plasmid was transfected into human choriocarcinoma JEG-3 cells. Only the upstream NRE (positions -619 to -597) was found to be functional in Ren-1d. The deletion of a 150-bp insertion from Ren-2d resulted in the suppression of chloramphenicol acetyltransferase activity to the level of Ren-1d expression. These data suggest that the upstream NRE that is functional in Ren-1d, but not in Ren-2d, may be partly responsible for differential expression of the renin genes in various tissues. The molecular mechanism of the NRE was examined by studying its interaction with nuclear proteins in submandibular gland and JEG-3 cells by gel-mobility-shift assays. Specific nuclear protein binding was observed only to the upstream NRE and the molecular mass of this protein was approximately 72 kDa as determined by Southwestern blot analysis. Thus our results suggest that both Ren-1d and Ren-2d conserve a cis-acting NRE in the 5' flanking region. In Ren-1d, this NRE could bind a specific nuclear protein resulting in the inhibition of Ren-1d expression in these tissues. On the other hand, the NRE in Ren-2d is nonfunctional due to interference by an adjacent 150-bp insertion. PMID- 1736304 TI - Genotypic analysis of mutations in Taq I restriction recognition sites by restriction fragment length polymorphism/polymerase chain reaction. AB - Point mutations in somatic cells play a role in the etiology of several classes of human pathologies. Experimental procedures are required that allow the detection and quantitation of such mutations in disease-related genes in tissue biopsy samples without the need for the selection of mutated cells. We describe the genotypic analysis of single base pair mutations in the Taq I endonuclease recognition sequence TCGA, residues 2508-2511 of exon 2 of the human c-H-ras1 gene, by the restriction fragment length polymorphism/polymerase chain reaction (RFLP/PCR) approach. The high thermostability of Taq I endonuclease allows the continuous removal of eventual residual wild-type sequences during the thermocycling of the PCR and reduces polymerase errors in the final RFLP/PCR product to a minimum. As few as five copies of a mutant standard containing two base pair changes in the chosen Taq I site could be rescued from 10(8) copies of wild-type DNA. Taq I RFLP/PCR holds promise for the monitoring of mutations in biochemical epidemiology. PMID- 1736305 TI - The third chromophore of DNA photolyase: Trp-277 of Escherichia coli DNA photolyase repairs thymine dimers by direct electron transfer. AB - Photolyases repair pyrimidine dimers in DNA by converting the light energy of 300 to 500-nm photons into chemical energy. Enzymes from various organisms contain two chromophore cofactors (FADH2 and either methenyltetrahydrofolate or 8-hydroxy 5-deazaflavin) that absorb the low-energy photons and initiate splitting of the cyclobutane ring by a radical mechanism. Here, we show that, in addition to these two chromophores, in the far UV range, direct excitation of one specific tryptophan residue (out of 15 total) in the polypeptide chain of Escherichia coli photolyase leads to splitting of the cyclobutane ring with high quantum yield (phi = 0.56), independent of the other chromophores. The specific tryptophan residue responsible for photosensitized repair was identified as Trp-277 by site specific mutagenesis. PMID- 1736306 TI - Function of specific 2'-hydroxyl groups of guanosines in a hammerhead ribozyme probed by 2' modifications. AB - The importance of the 2'-hydroxyl group of several guanosine residues for the catalytic efficiency of a hammerhead ribozyme has been investigated. Five ribozymes in which single guanosine residues were substituted with 2'-amino-, 2' fluoro-, or 2'-deoxyguanosine were chemically synthesized. The comparison of the catalytic activity of the three 2' modifications at a specific position allows conclusions about the functional role of the parent 2'-hydroxyl group. Substitutions of nonconserved nucleotides within the ribozyme caused little alteration in the catalytic activity relative to that obtained with the unmodified ribozyme. In contrast, when either of the guanosines within the single stranded loop between stem I and stem II of the ribozyme was replaced by 2' deoxyguanosine or 2'-fluoro-2'-deoxyguanosine, the catalytic activities of the resulting ribozymes were reduced by factors of at least 150. The catalytic activities of the corresponding ribozymes containing 2'-amino-2'-deoxyguanosine substitutions at these positions, however, were both reduced by factors of 15. These effects resulted from decreases in the respective kcat values, whereas variations in the Km values were comparatively small. A different pattern of reactivity of the three 2' modifications was observed at the guanosine immediately 3' to stem II of the ribozyme. Whereas both 2'-deoxyguanosine and 2' amino-2'-deoxyguanosine at this position showed catalytic activity similar to that of the unmodified ribozyme, the activity of the corresponding 2'-fluoro-2' deoxyguanosine-containing ribozyme was reduced by a factor of 15. The implications of these substitution-specific reactivities on the functional role of the native 2'-hydroxyl groups are discussed. PMID- 1736307 TI - Structural and enzymatic characterization of a purified prohormone-processing enzyme: secreted, soluble Kex2 protease. AB - The prohormone-processing Kex2 protease of the budding yeast Saccharomyces cerevisiae can be converted from an intracellular membrane protein to a soluble, secreted, and active form by deletion of the transmembrane domain and C-terminal tail. One such molecule was purified to near homogeneity from the culture medium of an overexpressing yeast strain. Amino acid sequence analysis revealed that the N terminus of mature Kex2 protease is created by a potentially autoproteolytic cleavage at Lys108-Arg109, prior to the domain homologous to subtilisin, followed by trimming of Leu-Pro and Val-Pro dipeptides by the Ste13 dipeptidyl aminopeptidase. Kinetic parameters were examined using fluorogenic peptidyl methylcoumarin amide substrates. Initial burst titration indicated that the preparation was entirely active. Measurements of dependence of activity on pH yielded a simple curve suggesting titration of a single ionizable group. Activity was half-maximal at pH 5.7 and nearly constant from pH 6.5 to 9.5. Discrimination between substrates was as great as 360-fold in Km and 130-fold in kcat. Substrates with a Lys-Arg dipeptide preceding the cleaved bond were preferred, having kcat/Km values up to 1.1 x 10(7) sec-1.M-1. The enzyme cleaved substrates having Arg-Arg, Pro-Arg, Ala-Arg, and Thr-Arg with increased Km but with unchanged kcat. In contrast, the enzyme displayed a dramatically lower kcat for a Lys-Lys substrate with a smaller increase in Km. Thus the two residues preceding the cleaved bond may play distinct roles in the selectivity of binding and cleavage of prohormone substrates. PMID- 1736308 TI - Syndecan expression regulates cell morphology and growth of mouse mammary epithelial tumor cells. AB - S115 mouse mammary epithelial cells lose their epithelial morphology and become tumorigenic when exposed to steroids. We have recently reported that testosterone exposure results in the suppression of syndecan expression, suggesting that this cell surface proteoglycan may influence S115 cell phenotype. We now report that a similar suppression and morphological response of S115 cells can be achieved by glucocorticoid exposure. We introduced into S115 cells an exogenous gene construct containing the full-length human syndecan cDNA under the control of a glucocorticoid-inducible retroviral promoter, in order to study the effect of syndecan expression on S115 cell behavior. Glucocorticoid-induced re-expression of syndecan in S115 cells restored an epithelial phenotype, while control transfectants and parental S115 cells exhibited an altered, nonepithelial phenotype. Moreover, the S115 cells expressing exogenous syndecan revealed a reduced ability to form colonies in soft agar. Therefore, the maintenance of epithelial morphology and normal growth of S115 cells are dependent on syndecan expression. PMID- 1736309 TI - Retinoic acid-dependent transactivation of major histocompatibility complex class I promoters by the nuclear hormone receptor H-2RIIBP in undifferentiated embryonal carcinoma cells. AB - H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex (MHC) class I genes. The binding occurs through the GG(T/A)CA motif present also in many other genes. The role of H-2RIIBP in developmental regulation of MHC class I genes has been studied in undifferentiated N-Tera2 embryonal carcinoma cells by transient cotransfection of an expressible H-2RIIBP plasmid and a chloramphenicol acetyltransferase reporter gene linked to the MHC class I promoter. Transfection of the expression plasmid led to production of H-2RIIBP transcripts and enhanced MHC class I promoter activity in cells that were treated with retinoic acid but not yet differentiated. Retinoic acid concentrations required for transactivation overlapped with those capable of inducing morphological differentiation and expression of endogenous MHC class I genes in these cells. This enhancement was mediated by region II, as a heterologous thymidine kinase promoter driven by region II also served as a target for H-2RIIBP transactivation. Deletion of the bulk of the DNA-binding domain or the ligand-binding domain of H-2RIIBP, but not of the N-terminal domain, abolished transactivation, indicating that the former two domains are critical for the enhancement. Moreover, H-2RIIBP transactivation exhibited a strict cell-type restriction. As observed in other cell lines, N Tera2 cells that had undergone differentiation failed to elicit transactivation, suggesting that H-2RIIBP acts in concert with a cofactor expressed in undifferentiated N-Tera2 cells that requires retinoic acid for its function. These results suggest that H-2RIIBP can function as a developmentally specific transcription factor for MHC class I genes. PMID- 1736310 TI - Structural analysis of a carcinogen-induced genomic rearrangement event. AB - We have explored the mechanism of genomic rearrangement in a hamster fibroblast cell culture system in which rearrangements are induced 5' to the endogenous thymidine kinase gene by chemical carcinogen treatment. The wild-type region around one rearrangement breakpoint was cloned and sequenced. With this sequence information, the carcinogen-induced rearrangement was cloned from the corresponding rearranged cell line by the inverse polymerase chain reaction. After the breakpoint fragment was sequenced, the wild-type rearrangement partner (RP15) was isolated by a second inverse polymerase chain reaction of unrearranged DNA. Comparison of the sequence of the rearrangement breakpoint with the wild type RP15 and 5' thymidine kinase gene regions revealed short repeats directly at the breakpoint, as well as nearby A + T-rich regions in each rearrangement partner. Pulsed-field electrophoresis analysis demonstrated that this rearrangement is an interstitial deletion of 35 kilobases. Southern blot analysis of the RP15 region in unrearranged parental cells showed a demethylated CpG island and a complex of DNase I-hypersensitive sites adjacent to the breakpoint in the region deleted by the rearrangement. Therefore, these studies reveal interesting sequence and chromatin features near the rearrangement breakpoints and suggest a role for nuclear organization in the mechanism of carcinogen induced genomic rearrangement. PMID- 1736311 TI - Analysis of CpG suppression in methylated and nonmethylated species. AB - The development of nearest-neighbor analysis led to the finding that the frequency of the dinucleotide CpG is markedly depressed in vertebrates. One explanation of this suppression is that methylation of CpG found in vertebrates represents a mutational hot spot through deamination of methylcytidine to thymidine. We have examined the role of methylated CpG as a factor in CpG suppression by comparing CpG distributions in coding regions of 121 genes from six species, three with methylated DNA and three with nonmethylated DNA. Overall base composition shows that all species exhibit CpG suppression, with the methylated forms showing significantly greater suppression than nonmethylated forms. When the data are analyzed by CpG position, the mean values of the methylated forms exhibit greater suppression than nonmethylated forms at positions I-II and II-III, but there is considerable overlap of suppression scores for individual species. At position III-I, CpG suppression is marked in all methylated species, and it is reversed in all nonmethylated species. Our analysis supports the hypothesis that CpG patterns at positions II-III and III-I in methylated forms are affected by mutation acting through deamination of methylcytidine to thymidine. We speculate that the excess of CpGs at position III I in nonmethylated forms may be related to a requirement for minimal thermal stability of the DNA. PMID- 1736312 TI - J chain synthesis and secretion of hexameric IgM is differentially regulated by lipopolysaccharide and interleukin 5. AB - Two functional polymeric forms of IgM can be produced by antibody-secreting B cells. Hexameric IgM lacks detectable J (joining) chain and activates complement 17-fold better than pentameric IgM, which usually contains one J chain per pentamer. Using the inducible B-cell lymphoma CH12, we determined if the synthesis of a particular polymeric form of IgM is a fixed property of B cells or can be altered. Lipopolysaccharide (LPS)-stimulated CH12 cells produced mixtures of IgM hexamers and pentamers, resulting in antibody with high complement-fixing activity. In contrast, interleukin-5-stimulated CH12 cells secreted predominantly pentameric IgM, with a correspondingly lower lytic activity. Differences in lytic activity were due only to the amount of hexameric IgM in the secreted antibody. Interleukin 5 stimulated higher production of J chain RNA and protein than LPS, while LPS induced the highest levels of the secretory form of mu protein. The amount of hexameric IgM secreted was therefore inversely proportional to the level of intracellular J chain protein in the responding B cells. We conclude that the biologic function of IgM produced by B cells differs depending on how they are stimulated and that this difference may be regulated by the relative availabilities of J chain and secretory mu proteins during IgM polymerization. PMID- 1736313 TI - Preservation of metabolic activity in lyophilized human erythrocytes. AB - Normal human erythrocytes (RBC) were freeze-dried under conditions that caused minimal modification in normal RBC metabolic activities. Because of the known effects of long-term storage on metabolic activities, we studied the effects of our lyophilization process on RBC metabolism. Of all the metabolic enzymes studied, only triosephosphate isomerase (D-glyceraldehyde-3-phosphate ketol isomerase, EC 5.3.1.1), enolase (2-phospho-D-glyceratehydro-lyase, EC 4.2.1.11), and pyruvate kinase (ATP:pyruvate O2-phosphotransferase, EC 2.7.1.40) were decreased when compared with fresh control nonlyophilized RBC. The activities of these enzymes did not differ significantly from those of blood bank RBC. Concentrations of high-energy intermediates, ATP, and 2,3-diphosphoglycerate, along with lactate and ATP production were decreased in lyophilized RBC. No enzymes of the pentose phosphate shunt were altered during lyophilization. In addition, our data show that lyophilized RBC possess an intact capacity to (i) synthesize adenine nucleotides and (ii) reduce MetHb to Hb and, thus, maintain the Hb in a functional physiologic state similar to fresh nonlyophilized RBC. The present study demonstrates the possibility of lyophilizing RBC in a manner that maintains normal metabolic and enzymatic function upon rehydration. PMID- 1736314 TI - Adaptive evolution of degrees and kinds of neoplastic transformation in cell culture. AB - Human cancers undergo protracted complex development from benign to malignant states, as most thoroughly documented in the mole-to-melanoma sequence. The early stages of the sequence tend to redifferentiate into normal tissues; the later stages progress to ever increasing multiplication and malignancy. When placed under the growth constraint of either crowding or low serum concentrations, the NIH 3T3 line of mouse cells readily undergoes transformation, expressed in the development of foci of cells that continue to multiply at confluence when the rest of the population has stopped. If the nontransformed cells are maintained for 3 months by frequent low-density passages in high concentrations of calf serum, they gradually lose the capacity to undergo transformation when the constraints are applied. The same conditions of passage have been used to reverse the transformation, both processes resembling in principle the reversal of the early stages of the mole-to-melanoma sequence. When the frequent low-density passages are made in high concentrations of fetal bovine serum, which supports a slightly lower growth rate than an equal concentration of calf serum, the degree of transformation is gradually increased, so that the foci become more numerous, broader, and thicker, reaching a maximum in successive assays at about 3 months of passaging. A diversity of focal morphologies is sporadically generated in the calf serum passage by exposing the cells to various concentrations of calf serum for 14 days of growth and confluency before assaying them. The dependence of the number, density, and morphology of foci on the environment in which the cells had been grown before assay reinforces the evidence that the transformation is an epigenetic process. The fact that these effects develop in culture gradually over an extended period of time suggests parallels to the characteristically long-term early regression and later progression, as well as the diversity of the mole-to melanoma sequence, and may also be representative of other cancers. PMID- 1736315 TI - Niobium/aluminum filters reduce patient exposure. AB - Reducing patient exposure while maintaining image quality is key to radiographers. In a comparison study of different filters, the authors found that a combined niobium/aluminum filter provides substantial reduction of entrance skin exposure with fairly small increases in tube loading and little loss of image contrast. PMID- 1736316 TI - Using qualitative research in radiologic technology. AB - Qualitative research is an underused methodology in radiologic technology that has valid applications for patient care, professional practice and education. This article discusses uses of qualitative methodology in the health professions and describes specific applications for the radiologic sciences. PMID- 1736317 TI - Continuing education: do mandates matter? AB - This study questions the assumption that radiographers lack the motivation to voluntarily participate in continuing professional education. Results of the author's survey of radiographers in 22 Central Florida hospitals--where state law mandates completion of 12 hours of CPE biannually--showed significant differences in participation due to motivational orientation and selected professional, educational and personal characteristics. PMID- 1736318 TI - Cadaver imaging proves valuable learning method. AB - In evaluating the project as a whole, students expressed feeling greater worthwhileness through participation in a special project. They enjoyed working as a team with faculty in an imaging environment and reported having fun and learning simultaneously. Also, students felt a sense of accomplishment in contributing to medical students' learning by participating in this service experience. This helped reinforce their role in health care and the need for cooperative relationships in medical education and practice. Based on student and faculty perceptions, this learning method is considered a valuable alternative to traditional means of performance practice and clinical education. The project's success is the result of: Its organization to meet the needs of both the service commitment and a learning environment. The motivational nature of a special voluntary experience alternative. The highly interactive and dynamic nature of the imaging sessions. The realistic feedback for performance with opportunity for analysis and improvement. While it is evident that a cadaver resource must exist to make such a project a viable option for radiography programs, those with such a resource should consider integrating it with the more traditional learning methods. Many program sponsors may have similar resources available in their environments for projects that provide imaging services as well as unique learning laboratories for radiography students. Close interaction with health educators and researchers along with creative investigation may reveal opportunities for special projects. PMID- 1736319 TI - Medical imaging improved beyond belief. PMID- 1736320 TI - Learning theories: something for everyone. PMID- 1736321 TI - The forces behind accreditation. PMID- 1736322 TI - In search of fungus artifactus. PMID- 1736323 TI - Postsynaptic potentiation and desensitization at the vertebrate end-plate receptors. PMID- 1736324 TI - Movement, posture and equilibrium: interaction and coordination. PMID- 1736325 TI - Development of serotoninergic system in the brain and spinal cord of the chick. AB - (1) Development of serotonin positive cells and fibers was immunohistochemically studied by the use of an antibody against serotonin. (2) Serotoninergic neurons were first observed in the immature rohmbencephalon raphe nuclei on embryonic day (E)4, where two clusters of serotonin positive neurons were located: one observed at the rostral part of the rohmbencephalon corresponding to the dorsal raphe nuclei had many serotonin positive cells: the other located at the caudal part of the rohmbencephalon corresponding to the medullary raphe nuclei of the adult animals had only a small number of serotoninergic cells. (3) By E8 the number of serotonin positive cells in the brain stem increased, and virtually all the raphe nuclei found in an adult animal were located. (4) Serotonin positive fibers in the marginal layer reached up to the diencephalon and telencephalon on E6 and E8, respectively. (5) Serotonin positive cells were found beside the midline regions in the ventral part of the spinal cord of the embryonic as well as posthatching chick. (6) Because almost all the serotoninergic fibers in the spinal cord originated from the brain stem raphe nuclei, propriospinal serotonin positive cells were considered as phylogenetic vestiges. (7) Serotoninergic fibers were first found in the marginal layer of the cervical and lumbar spinal cord on E6 and E8, respectively. (8) There was a waiting period of a few days before they penetrated into the mantle layer. (9) Terminal arbolization of the serotoninergic fibers started from late embryonic periods (E16 less than), and was maximized within one week of hatching. (10) Thereafter the density of serotonin positive fibers decreased in all the regions of the spinal cord. (11) Developmental changes of the density of serotonin determined with a high performance liquid chromatography were the same as those determined through immunohistochemistry. Namely the density of serotonin increased linearly from E6 to hatching period, and reached the maximum value one week posthatching. (12( The density of the serotonin in the adult spinal cord was about half of the maximum value. (13) It is to say that the densities of serotonin and serotoninergic fibers transiently increased around one week posthatching. (14) Following the transient increase serotoninergic fibers were eliminated from the neuropil, the fibers were localized in the specific regions of the motor nucleus: motor neuron pools of extensor muscles of the hip joint in the lumbosacral spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1736326 TI - Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group. AB - Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy (55/59), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoral bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases. PMID- 1736327 TI - Intraluminal low-dose rate brachytherapy for malignant endobronchial obstruction. AB - From October 1985 through October 1989, 87 patients underwent 105 intraluminal brachytherapy treatments for endobronchial or endotracheal malignant tumors. Low dose rate iridium-192 seeds were used. Of the 60 patients treated for primary lung carcinoma, 52 patients (87%) had previously received full-course external beam radiotherapy to the tumor sites. Ten patients were treated for symptomatic metastatic disease, and one patient had extension of tumor into the trachea from carcinoma of the cervical esophagus. Clinical or bronchoscopic improvement was noted in 42 patients (59%). No significant difference in the response rate was observed between various types of tumor. Patients who were treated with a radiation dose larger than 2500 cGy at a 2 cm radius had a significantly greater response rate (77%) than patients treated with a dose less than 2500 cGy (38%) (p = 0.001). A trend toward better results was apparent in patients who had undergone Nd:YAG laser bronchoscopy in the 2 weeks before brachytherapy. The treatments were well tolerated, and the incidence of serious complications was low and acceptable. PMID- 1736328 TI - Elevation of mouse kidney thiol content following administration of glutathione. AB - We have found that kidney glutathione and cysteine content in C3H mice can be increased by intraperitoneal administration of either glutathione (GSH) or glutathione disulfide (GSSG). Kidney thiol content is maximal 20-60 min after administration of 1000 mg/kg glutathione and returns to normal values by 2 h. The same time-course of thiol perturbation was observed when acivicin, an inhibitor of gamma-glutamyl transpeptidase, was administered 15 min prior to GSSG administration. The increase in kidney thiols after GSSG administration appears to saturate, with little additional increase as the administered dose is increased above 750 mg/kg. There was no significant change in liver GSH or cysteine after GSSG administration. We suggest that glutathione administration may provide a strategy for selective radioprotection or chemoprotection of specialized cells which can effectively utilize systemic GSH precursors. PMID- 1736329 TI - The effect of two fractions of radiation, delivered in air or in hyperbaric oxygen, on the Fib/T tumour in WHT mice pretreated with a hypoxic gas mixture. AB - The response of the Fib/T tumour to equal fractions of radiation, spaced by an interval of 24 hours, was determined in tumour-bearing mice that were pretreated either with 8% oxygen for 48 h or with air. An increase in tumour cell kill occurred in the group of animals that received a low oxygen pretreatment. Tumour cell kill was further and significantly increased if mice were retained in the low oxygen environment for the 24-h interval between radiation fractions. Possible explanations for these findings are proposed and discussed. The effect of a 48 h 8% oxygen exposure in modifying the response of the Fib/T tumour to two fractions of radiation, both delivered in hyperbaric oxygen, was also investigated. The low oxygen pretreatment did not significantly alter the tumour response to radiation given under conditions of hyperbaric oxygenation. PMID- 1736330 TI - Fractionation response and repair kinetics of radiation-induced heart failure in the rat. AB - Local heart irradiation with single or fractionated doses leads to heart failure after dose-dependent latency times. Clinical symptoms of heart failure are dyspnoea at rest, apathy and subcutaneous oedema. Animals autopsied when they presented with these symptoms, have a congested liver and occasional pleural effusions. The left ventricle is dilated, showing a reduction in wall thickness by 15-17% of control values. Histological examination reveals a focal degeneration and necrosis of about 23% of the total myocardial volume. Loss of alkaline phosphatase activity from myocardial capillaries, which is known to precede myocardial degeneration, involves 77% of the myocardium. These findings at the time of manifest heart failure are constant, independent on whether injury to the heart was inflicted by single-dose or fractionated irradiation or whether heart failure developed within a relatively short time after high total doses or within many months after low total doses. The latent time of heart failure therefore can be considered an appropriate endpoint for comparison of treatment groups. From experiments giving 1, 2, 4, or 10 dose fractions, a low alpha/beta ratio of 3.7 Gy (95% confidence interval 1.8-5.6 Gy) can be calculated. When the time interval between dose fractions is varied in a split-dose experiment, time intervals of up to 3 h do not increase the survival time significantly. This appears to indicate very slow repair of sublethal damage. On the other hand, it cannot be excluded that pathogenetic mechanisms independent of cell death in the renewing cell population contribute to this effect, making an interpretation of the alpha/beta ratio in terms of cell survival parameters of a defined target cell population difficult. PMID- 1736331 TI - Late radiation response of canine mediastinal tissues. AB - The mediastinal tissues which included heart, lung, trachea and esophagus of 70 adult beagle dogs were irradiated to a range of total radiation doses between 24 and 68 Gy given in 2, 3 and 4 Gy fractions. The purpose of the study was the calculation of alpha/beta ratios for morphologic and functional changes of the mediastinal tissues. Functional assays including echocardiography, electrocardiography, right heart hemodynamics and cardiac output were performed. Histomorphometric analyses of all tissues included in the field were done 2 years after treatment. Euthanasia was performed on 7 of 70 dogs prior to 2 years due to congestive heart failure and seven other dogs had signs of heart failure 2 years after treatment. Heart failure was thought to be caused by either pericardial effusions or constrictive pericarditis in these dogs. Heart failure occurred at doses of 62 and 68 Gy given in 2 Gy fractions, 60 Gy given in 3 Gy fractions and 52 Gy given in 4 Gy fractions. The ED50 values for pericardial fibrosis for 2, 3 and 4 Gy fractions were 46.1, 43.9 and 26.6 Gy, respectively. An alpha/beta ratio of 2.5 Gy was calculated by direct quantal response analysis. Small foci of myocytolytic lesions were detected in 11 dogs. Calculated ED50 values for myocytolysis were 70.4 Gy given in 2 Gy fractions and 50.8 Gy given in 4 Gy fractions. The estimated alpha/beta ratio was 3.2 Gy. Heart rates determined from physical examination and frequency of S-T segment changes increased with increasing dose. No other dose related changes were found in any of the other functional parameters. Functional changes were detected in the 14 dogs with clinical signs of heart failure. Focal consolidation and subpleural fibrosis were present in the irradiated lung volume. These late changes had no detectable physiologic effect in these dogs because of the small volume of lung irradiated. The ED50 values for lung consolidation were 54.3, 45.8 and 26.6 Gy after 2, 3 or 4 Gy fractions, respectively. The estimated alpha/beta ratio was 3.4 Gy. No dose related changes could be detected in the trachea or esophagus at 2 years after treatment. These results demonstrate that lung and pericardium are the most responsive tissues in the mediastinum within the first 2 years after treatment. Myocardial lesions were present with high ED50 values, but were not found to be functionally significant at 2 years after irradiation. Human clinical data indicate that longer observation periods are needed for development of these lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1736332 TI - Dose escalation for stage C (T3) prostate cancer: minimal rectal toxicity observed using conformal therapy. AB - The treatment of stage C (T3) adenocarcinoma of the prostate using external beam radiation therapy (RT) reportedly achieves clinical local control of approximately 70-80%. A dose relationship to local control has been demonstrated in prostate cancer, although a dose-related increase in complications has also been observed. To determine the maximum dose deliverable to the prostate gland while maintaining an acceptable complication rate, a prospective dose-escalation trial using a conformational planning and dose-delivery technique was initiated for patients with stage C (T3) disease. Initial results reported here are encouraging. PMID- 1736333 TI - Curietherapy versus external irradiation combined with curietherapy in stage II squamous cell carcinoma of the mobile tongue. PMID- 1736334 TI - Reirradiation of recurrent head and neck cancers: external and/or interstitial radiation therapy. AB - Recurrent cancer in the head and neck is not an uncommon clinical problem. The average cure rate of these patients has been reported to vary between 30 and 40% and most failures are due to locoregional relapses. After a previous full course of radiation, surgery is the salvage modality of choice; however, if surgery was not feasible for whatever reason, reirradiation has been offered to some patients. To establish the role of reirradiation in head and neck cancer, we analyzed a 13-year experience with patients reirradiated in the DDHCC. The reirradiation was performed between 1970 and 1980 by means of external beam radiation therapy (ERT series; n = 55) and between 1985 and 1988 by external radiation combined with interstitial radiation therapy (IRT +/- ERT series; n = 18). A minimum follow-up of 3 years was allowed for. An improvement in local control was observed (50% vs. 29%) for the IRT +/- ERT series and the ERT series, respectively. The improvement in local control was not reflected in a survival benefit; i.e. an actuarial overall survival of 20% at 5 years was observed in both series. No treatment-related deaths occurred. However, for the patients that were controlled at the reirradiated site, 28% (4/16 of the ERT series and 3/9 of the IRT +/- ERT series) did experience severe side effects. PMID- 1736335 TI - Endosonographic diagnosis of submucosal upper gastrointestinal tract tumors. AB - Endoscopic ultrasound (EUS) was performed in 37 patients with upper gastrointestinal tract submucosal tumors (SMT). Fourteen of these were located in the esophagus, 20 in the stomach, and 3 in the duodenum. In 26 patients histologic confirmation was achieved by operation (n = 15) or biopsy/puncture (n = 11). EUS was able to visualize all tumors and, with one exception, determined their originating wall layer correctly. It became evident that myogenic tumors arise from the echo-poor layers (second layer and fourth--that is, muscularis propria) and that other lesions, such as cysts or fibromas, originate from the third, echo-rich layer (submucosa). Tumor size was correctly (+/- less than 5 mm) predicted in 87% of cases. Computed tomography, performed in 22 patients, was successful in visualizing the SMT in only two-thirds of cases. No single endosonographic criterion could be obtained which enabled accurate differentiation between benign and malignant SMT. However, from a clinical point of view, it seems reasonably safe to regard smaller (less than 3 cm), smoothly demarcated SMT as benign and follow them up by repeated EUS, especially in patients at risk for surgery. Larger masses (greater than 5 cm) and those with irregular borders should be suspected of being malignant. In the future, application of new, small ultrasound probes that can be used during conventional endoscopy (two SMT were visualized successfully) may greatly simplify the procedure. PMID- 1736336 TI - Effect of duodenal ulcer healing induced by omeprazole and ranitidine on the generation of gastroduodenal eicosanoids, platelet-activating factor, pepsinogen A, and gastrin in duodenal ulcer patients. AB - The effect of duodenal ulcer healing induced by omeprazole on gastroduodenal generation of eicosanoids, platelet-activating factor (PAF), pepsinogen A, and gastrin was evaluated. Sixty patients with endoscopically proven duodenal ulcer were randomized to receive 20 mg omperazole once daily or 300 mg ranitidine at bedtime for 2 weeks. Patients whose ulcers did not heal were treated for an additional 2 weeks. Endoscopic biopsy specimens and serum samples were obtained before and after treatment. There was no significant difference in the healing rate between the two treatment modalities. At 2 weeks healing rates were 60% and 56% in the omperazole and ranitidine groups, respectively, whereas at 4 weeks the respective healing rates were 96% and 86%. Ulcer healing induced by omeprazole and ranitidine was not accompanied by significant changes in mucosal leukotriene B4 or C4 generation. Mucosal PAF significantly decreased in patients treated with omeprazole for 4 weeks. In omperazole-treated patients there was a trend towards increase in mucosal prostaglandin E2 generation which was significant in the fundus after 4 weeks of treatment. After 2 weeks of omeprazole treatment, serum gastrin and pepsinogen A levels almost doubled when compared with their pretreatment levels. In conclusion, duodenal ulcer healing with 20 mg omeprazole daily is not superior to healing rates with 300 mg ranitidine at bedtime after both 2 and 4 weeks of treatment. In omeprazole-treated subjects ulcer healing was accompanied by a significant decrease in mucosal PAF generation and increased levels of serum gastrin and pepsinogen A. PMID- 1736337 TI - Effect of Helicobacter pylori on serum pepsinogen I and plasma gastrin in duodenal ulcer patients. AB - Duodenal ulcer patients have increased serum pepsinogen I (PGI) concentrations and an increased prevalence of Helicobacter pylori infection. We have examined the effect of eradicating the infection on PGI. In 12 duodenal ulcer patients in whom H. pylori was successfully eradicated, the median basal PGI was 90 ng/ml (range, 37-252) before treatment and fell to 74 ng/ml (28-197) 1 month after treatment (p less than 0.01). In 12 patients in whom therapy failed to eradicate the infection, the PGI was 87 ng/ml (35-128) before treatment and remained unchanged at 83 ng/ml (36-119) 1 month after treatment. In the group with successful eradication the median basal plasma gastrin was 43 ng/l (15-95) before treatment and fell to 30 ng/l (17-75) 1 month after treatment (p less than 0.003), but there was no change in the corresponding values in the group without eradication (55 ng/l; range, 25-120, and 45 ng/l; range, 5-175; p = 0.9). In conclusion, eradication of H. pylori results in a fall in PGI and plasma gastrin, and these changes are not due merely to the anti-H. pylori drugs themselves or to discontinuation of previous ulcer therapy. PMID- 1736338 TI - Breath methane and colorectal cancer. AB - The association between colorectal cancer and breath methane is controversial. We compared a group of 59 patients with unresected colorectal cancer with a group of control subjects matched for age and sex. We also studied 43 of the cancer patients before and 3-6 months after resection. Sixty-three per cent of the patients with unresected carcinoma and 56% of the control subjects were methane excretors (NS). We found no significant change in methane excretion status after resection. Because recent colonic cleansing has been shown to influence methane production in the colon, 15 breath methane excretors were studied immediately before the start of cleansing, on the day of colonoscopy, and on the 7th day thereafter. Forty per cent became breath-methane-negative on the day of colonoscopy, but all 15 were excretors with a median of 60% of the precleansing concentration on the 7th day. The present study does not confirm an association between breath methane and colorectal cancer. It is unlikely that colonic cleansing procedures influenced the results of this study. PMID- 1736339 TI - Adrenergic and cholinergic regulation of gastric mucus phospholipid secretion. AB - The influence of adrenergic and cholinergic agonists on phospholipid secretion in gastric mucosal cells maintained in the presence of [3H]choline was investigated. The secretion of [3H]choline phospholipids over a 30-min period averaged 1.98% of the total cellular labeled phospholipids in the absence of any mediator and was enhanced by the beta-adrenergic agonist isoproterenol to a greater extent than by the cholinergic agonist pilocarpine. A 2-fold increase in phospholipid secretion was achieved with isoproterenol, whereas pilocarpine produced a 1.3-fold increase. The stimulatory effect of isoproterenol was inhibited by alprenolol, and that of pilocarpine by atropine. The phospholipids secreted in response to isoproterenol showed a 30% decrease in lysophosphatidylcholine, whereas a 2.1 fold enrichment in this phospholipid occurred with pilocarpine. The results demonstrate the involvement of neural mediators in the regulation of phospholipid secretion in gastric mucus. PMID- 1736340 TI - DNA ploidy, S-phase fraction, and G2 fraction as prognostic determinants in human pancreatic cancer. AB - The DNA ploidy, S-phase fraction (SPF), and G2 fraction of pancreatic cancer tissue was measured by flow cytometry in 95 patients. Forty-nine per cent (n = 47) had a diploid DNA index, and 51% (n = 48) of tumours were aneuploid. Aneuploid tumours and high-grade tumours had significantly higher S-phase and G2 fraction values than diploid tumours or low-grade tumours. Diploid and tetraploid tumours had a more favourable prognosis than non-tetraploid aneuploid tumours (p = 0.0020) during the mean follow-up of 6 years. The type of therapy (p = 0.07), histologic grade (p = 0.06), SPF (p = 0.1), and G2 fraction (p = 0.02) had predictive value in survival analysis as well. In multivariate survival analysis, including flow-cytometric, histologic, and clinical variables, diploidy and tetraploidy had independent predictive value. The results suggest that flow cytometry might be used in grading of pancreatic cancer. Such a grading would have practical value if new modes of therapy are being developed. Forty-one per cent of multiple samples had a heterogeneous DNA index when multiple samples were used. Consequently, flow cytometric analysis of pancreatic cancer using multiple samples is recommended. PMID- 1736341 TI - Nocturnal gastric secretion in duodenal ulcer patients and healthy controls. Ranges and reproducibility. AB - The nocturnal gastric acid secretion of 22 male duodenal ulcer patients was compared with that of 47 healthy male volunteers. Median nocturnal acid output was greater in duodenal ulcer patients (55 mmol versus 33 mmol 10 h-1; p = 0.013), but there was almost complete overlap of the ranges. Five duodenal ulcer patients and three volunteers had nocturnal outputs of acid previously considered to be pathognomonic of the Zollinger-Ellison syndrome in the absence of other evidence of a gastrinoma. Nineteen healthy volunteers underwent a repeat study to assess the reproducibility of nocturnal gastric acid output. Median intraindividual variability (+/- distribution-free 95% confidence limits) was 23% (-34% to +72%). Studies of nocturnal gastric secretion are of no diagnostic value, and their variability should be taken into consideration when evaluating gastric antisecretory drugs. PMID- 1736342 TI - Causes of death during the first 5 years of a randomized trial of mass screening for colorectal cancer with fecal occult blood test. AB - The main purpose of population screening for colorectal cancer is to reduce mortality from the disease. The criteria of death from colorectal cancer are defined in the present randomized trial of 61,938 persons between 45 and 74 years old, and the need for an impartial death review committee was demonstrated. Causes of death within the first 5 years are described within subgroups of the test group and compared with those in the control group. Death rates were higher among non-responders to screening than among controls and among those in whom Hemoccult-II had been performed at least once. Persons with negative Hemoccult-II had a lower death rate than controls. The overall autopsy rate was 32%. Lethal complications from treatment of colorectal neoplasia were evaluated per se. Death from colorectal cancer occurred in 74 persons in the total screening group and in 91 among controls. Sources of bias are discussed. A method of evaluating possible benefit to those being screened is suggested. Final results cannot be expected before 1996. PMID- 1736343 TI - Effects of acute psychologic stress on small-intestinal motility in health and the irritable bowel syndrome. AB - Psychologic stress may be a provoking factor in the alterations in phase-2 motor activity of the migrating motor complex (MMC) which have been recorded in patients with the irritable bowel syndrome (IBS). To test this, changes in phase 2 duodenojejunal motor activity during 20 min of psychologic stress in 10 patients with IBS were compared with those shown by 10 healthy subjects. Autonomic arousal in response to the stressor was assessed by cardiovascular responses and self-reported levels of anxiety and tension. IBS and controls showed a significant cardiovascular and subjective response to stress which was comparable in the two groups. In general, duodenal phase-2 motor activity was suppressed during stress in both IBS and controls. Jejunal motor activity showed a similar inhibitory response in both groups, but the change in motility index was significant for controls only. Qualitatively, stress did not cause clustered contractions in either the IBS or the control group. However, in IBS patients with clustered contractions in the basal period there was inhibition of this pattern during stress. These findings suggest that acute psychologic stress profoundly suppresses, rather than enhances, duodenojejunal MMC phase-2 motility in healthy subjects. IBS patients, irrespective of their underlying phase-2 motor pattern show similar, although less marked, changes in motility. PMID- 1736344 TI - Reliability of in situ measurements of colorectal polyps. AB - A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of the polyp the area of the polyp on the picture can be calculated by computerized analysis. To test the reliability and sensitivity of these two in situ measurements, 43 colonic polyps (mean diameter, 8.5 mm; range, 4-20 mm) removed by snare diathermy resection were examined. The maximal diameter was measured, and two Polaroid pictures taken of each polyp. After polypectomy each polyp was subjected to extracorporeal reassessment of diameter and measurement of weight and volume. By computerized analysis of the pictures the following variables were estimated: 1) area of the polyp on the picture; 2) largest diameter; 3) maximum width 90 degrees on the largest diameter; 4) maximum distance from centre of gravity; and 5) minimum distance from centre of gravity. Results showed good correlation between diameter measured in situ and after removal (r = 0.93), diameter raised to the 3rd power and weight (r = 0.93), and also to volume (r = 0.77). Area analysis compared with weight was less good (r = 0.72). A very high correlation was demonstrated between weight and volume (r = 0.99). We conclude that the measurement of diameter in situ with a measuring probe is sensitive and somewhat more reliable than computerized analysis of size. The present 3-year follow-up and intervention study will show which of the two methods is preferable for evaluation of polyp growth. PMID- 1736345 TI - Unilateral vagal denervation suppresses omeprazole-induced trophic effects on the denervated side of the rat stomach. AB - In several experimental animals treatment with large doses of the proton pump inhibitor omeprazole leads to hypergastrinemia and with time to trophic effects in the acid-producing part of the stomach, most notably an increased density of the histamine-producing enterochromaffin-like (ECL) cells. The trophic effects are thought to reflect the increase in circulating gastrin. In the present study unilateral vagal denervation in the rat partly suppressed the tropic effects seen in the denervated side of the stomach but not those in the intact side after treatment with omeprazole for 10 weeks. Unilateral vagal denervation significantly reduced the proliferative stimulus of omeprazole on the ECL cells in the denervated part of the stomach. Thus, an intact vagal innervation appears to be essential for the capacity of the oxyntic mucosa, including the ECL cells, to respond to elevations in serum gastrin. We suggest that gastrin and the vagus interact to maintain trophic control of the oxyntic glands. PMID- 1736346 TI - Radiolucent and calcified pancreatic lithiasis: two different diseases. Role of alcohol and heredity. AB - One hundred and eighteen consecutive patients presenting with pancreatic calculi have been studied by means of plain films of the abdomen and endoscopic retrograde cholangiopancreatography. Patients were divided into the following groups: 1) Evenly calcified calculi, 74 patients, 66 men, aged at onset (M +/- SM) 40 +/- 10 years; daily consumption of alcohol, 157 +/- 121 g, and of tobacco, 26 +/- 15 cigarettes. Two patients presented with another case in the same family. Composition of calculi--at least 95% calcium salts and a degraded form of lithostathine S (formerly called PSP S2-5)--was similar in the Occidental alcoholic and in the tropical form: calcified calculi are probably related to alcohol and nutritional disorders. 2) Radiolucent stones, 17 patients, 12 men and 5 women, aged at onset 38 +/- 18 years. These patients had a low alcohol and tobacco consumption. There were four familial cases. 3) Radiolucent core with a calcified shell (target calculi), 27 cases, 23 men; age at onset, 38 +/- 15 years; daily ethanol consumption, 111 +/- 93, and tobacco, 19 +/- 15 cigarettes. There were two familial cases. It has been shown that these calculi originated from transparent calculi that later calcified. The frequency of women and of familial cases was significantly greater in groups 2 + 3 than in group 1. The consumption of alcohol and tobacco and the proportion of men were significantly lower in group 2 than in groups 1 and 3. We discuss the role of heredity in lithostathine precipitation and of alcohol in calcium precipitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736347 TI - Experimental clogging of biliary endoprostheses. Role of bacteria, endoprosthesis material, and design. AB - The major problem facing patients treated with biliary endoprostheses is their frequent clogging, necessitating their exchange. Clogged endoprostheses contain mainly bacteria embedded in an amorphous proteinaceous material with the occasional presence of food fibres. We studied this problem in an in vitro model, evaluating the role of bacteria, endoprosthesis design, and material in sludge formation. We found endoprostheses perfused with artificially contaminated bile to contain significantly more sludge than those perfused with sterile bile (p less than 0.05). The amount of sludge varied with the bacterial species used. Endoprostheses perfused with bacteria producing beta-glucuronidase were not associated with a particularly large amount of sludge. Endoprostheses with side holes contained significantly more sludge than those without (p less than 0.05). Furthermore, endoprostheses made of material with a low friction coefficient, such as Teflon, contained significantly less sludge than endoprostheses made of materials with a higher friction coefficient, such as polyethylene and polyurethane (p less than 0.05). These results emphasize the role of bacteria in endoprostheses clogging and clearly demonstrate the harmful effect that side holes have on endoprosthesis function. PMID- 1736348 TI - A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis. AB - The aim of this study was to evaluate whether budesonide enema (2 mg/100 ml) had a significantly better effect than placebo in the treatment of distal ulcerative colitis or proctitis. The trial was of controlled, randomized, double-blind design and included 41 treated patients. The treatment time was 4 weeks, with revisits after 2 and 4 weeks. If no improvement was seen, the patient could be switched over to open-label therapy with budesonide enema. Sigmoidoscopy, histology, blood chemistry, and diary cards were used for estimating the effect of treatment. The results showed that budesonide was superior to placebo. Sigmoidoscopy and biopsy scores improved significantly (p less than 0.01) in budesonide-treated patients compared with placebo. Significantly more patients switched over to open budesonide treatment in the placebo group owing to lack of efficacy compared with budesonide (p less than 0.001). No drug-related adverse experiences occurred, and there was no decrease in endogenous morning plasma cortisol levels. It is concluded that budesonide enema appears to be an effective and safe treatment for distal ulcerative colitis and proctitis. PMID- 1736349 TI - PCR amplification of specific alleles. PMID- 1736350 TI - The medfly in California. PMID- 1736351 TI - The medfly in California. PMID- 1736352 TI - Transmittal of hepatitis C. PMID- 1736353 TI - Anti-cancer drug IL-2 may finally be approved. PMID- 1736354 TI - Roche eases PCR restrictions. PMID- 1736355 TI - NIH's vision runs into political reality. PMID- 1736356 TI - Determining what immune cells see. PMID- 1736357 TI - New theory of diabetes etiology riles immunologists. PMID- 1736358 TI - Priming the brain's language pump. PMID- 1736359 TI - Working memory. AB - The term working memory refers to a brain system that provides temporary storage and manipulation of the information necessary for such complex cognitive tasks as language comprehension, learning, and reasoning. This definition has evolved from the concept of a unitary short-term memory system. Working memory has been found to require the simultaneous storage and processing of information. It can be divided into the following three subcomponents: (i) the central executive, which is assumed to be an attentional-controlling system, is important in skills such as chess playing and is particularly susceptible to the effects of Alzheimer's disease; and two slave systems, namely (ii) the visuospatial sketch pad, which manipulates visual images and (iii) the phonological loop, which stores and rehearses speech-based information and is necessary for the acquisition of both native and second-language vocabulary. PMID- 1736360 TI - Experimental phylogenetics: generation of a known phylogeny. AB - Although methods of phylogenetic estimation are used routinely in comparative biology, direct tests of these methods are hampered by the lack of known phylogenies. Here a system based on serial propagation of bacteriophage T7 in the presence of a mutagen was used to create the first completely known phylogeny. Restriction-site maps of the terminal lineages were used to infer the evolutionary history of the experimental lines for comparison to the known history and actual ancestors. The five methods used to reconstruct branching pattern all predicted the correct topology but varied in their predictions of branch lengths; one method also predicts ancestral restriction maps and was found to be greater than 98 percent accurate. PMID- 1736361 TI - Ordered self-assembly of polypeptide fragments to form nativelike dimeric trp repressor. AB - Subdomain-size proteolytic fragments of Escherichia coli trp repressor have been produced that assemble in defined order to regenerate fully native dimers. By characterization of the secondary and tertiary structures of isolated and recombined fragments, the structure of assembly intermediates can be correlated with the kinetic folding pathway of the intact repressor deduced from spectroscopic measurement of folding rates. The nativelike structure of these intermediates provides further evidence that protein folding pathways reflect the stabilities of secondary structural units and assemblies found in the native state. The proteolytic method should be generally useful in adding structural detail to spectroscopically determined folding mechanisms. PMID- 1736362 TI - Toward a dynamical structure of DNA: comparison of theoretical and experimental NOE intensities. AB - Comparisons of experimental and calculated interproton nuclear Overhauser effect (NOE) buildup curves for duplex d(CGCGAATTCGCG)2 have been made. The calculated NOEs are based on molecular dynamics simulations including counterions and water and on the single-structure canonical A, B, and crystal forms. The calculated NOE effects include consideration of the motions of individual interproton vectors and the anisotropic tumbling of the DNA. The effects due to inclusion of anisotropic tumbling are much larger than those due to the local motion, and both improve the agreement between calculated and experimental results. The predictions based on the dynamical models agree significantly better with experiment than those based on either of the canonical forms or the crystal structure. PMID- 1736363 TI - The Son of sevenless gene product: a putative activator of Ras. AB - The Son of sevenless (Sos) gene functions in signaling pathways initiated by the sevenless and epidermal growth factor receptor tyrosine kinases. The Sos gene has now been isolated and sequenced. Its product is a 1595-amino acid protein similar to the CDC25 protein in Saccharomyces cerevisiae, a guanine nucleotide exchange factor that activates Ras. These results imply a role for the ras pathway in Drosophila neuronal development. PMID- 1736365 TI - Myelodysplastic syndromes: introduction. PMID- 1736364 TI - Linguistic experience alters phonetic perception in infants by 6 months of age. AB - Linguistic experience affects phonetic perception. However, the critical period during which experience affects perception and the mechanism responsible for these effects are unknown. This study of 6-month-old infants from two countries, the United States and Sweden, shows that exposure to a specific language in the first half year of life alters infants' phonetic perception. PMID- 1736366 TI - Biology and pathogenesis of the myelodysplastic syndromes. PMID- 1736367 TI - Chromosome abnormalities in myelodysplastic syndromes. PMID- 1736368 TI - In vitro marrow culture studies in the myelodysplastic syndromes. PMID- 1736369 TI - Classification and morphologic features of the myelodysplastic syndromes. PMID- 1736370 TI - Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure. AB - The median latency of 2 degrees MDS/AL is 4 to 5 years. A high percentage of patients with 2 degrees MDS/AL convert to 2 degrees AL. Survival of either is less than 1 year. A constellation of morphologic abnormalities from all 3 cell lines produces a unique appearance. Both 2 degrees MDS and 2 degrees AL are difficult to classify by the FAB system. With the exception of the identification of karyotypic abnormalities, the biology of 2 degrees MDS/AL remains largely unexplored. Alterations of chromosomes 5 and 7 predominate, but other associated cytogenetic abnormalities are being increasingly recognized. A synthesis of data regarding 2 degrees MDS/AL resulting from the treatment of several primary malignancies generates the tentative conclusions that (a) many of the alkylating agents, and the nonclassic alkylating agent procarbazine, are leukemogens; (b) melphalan is a more potent leukemogen than cyclophosphamide. None of the other alkylating agents has been clearly established to be more or less potent than another; (c) increasing duration or amount of alkylator-based chemotherapy increases the risk of leukemogenesis; (d) low doses of radiation delivered to large volumes of bone marrow are weakly leukemogenic. High doses of radiation delivered to small volumes are not. Due to the latter, there is minimal additive risk for 2 degrees MDS/AL among studies using alkylator-based chemotherapy and radiotherapy, either concurrently or sequentially; (e) the older patient (greater than 40) is at increased risk for 2 degrees MDS/AL, at least in Hodgkin's disease. Children may be at lesser risk than adults, and younger children at lesser risk than older children; (f) the risk of 2 degrees MDS/AL peaks within the first decade after treatment for the primary malignancy. The incidence rates during the second decade are low. Identified occupational/environmental risks for 2 degrees MDS/AL include benzene, ambient and diagnostic radiation exposure, and perhaps ethylene oxide. The similarities in karyotype abnormalities among leukemic cells of those whose occupations expose them to chemical hazard, and those who are exposed to cytotoxic agents, suggest that many more environmental leukemogens have yet to be discovered. Karyotype is an important prognostic factor for both achievement of CR and for survival. Nonaggressive treatment approaches have not proven useful, although the use of hematopoietic growth factors offers promise in this area. Combination chemotherapy is justified in patients with adequate performance statuses and "favorable" karyotypes. Allogeneic bone marrow transplantation is currently the only curative approach, and can be applied without attempts to first reduce the leukemic burden. PMID- 1736371 TI - Chemotherapy and bone marrow transplantation for myelodysplastic syndromes. PMID- 1736372 TI - Duplex sonography of the carotid arteries. AB - Duplex sonography is the best noninvasive modality for investigation of possible carotid artery stenosis. By using the above described techniques, almost all significant stenoses can be detected and categorized correctly. Knowledge of common pitfalls in the performance and interpretation of the examination is essential to avoid misdiagnosis. Color imaging is a helpful addition to conventional duplex imaging, but is not essential to the performance of high quality examinations. PMID- 1736373 TI - Peripheral arterial duplex ultrasonography. PMID- 1736374 TI - Pseudotruncus arteriosus (type I). PMID- 1736375 TI - Ultrasound evaluation of deep venous thrombosis. AB - Ultrasonography has achieved the role of the contemporary diagnostic tool for the assessment of DVT. Routine use of venography to assess for lower extremity clot is very difficult to justify. Long-term follow-up of patients has provided sufficient documentation that ultrasonography can successfully supplant the venogram. Only with regard to calf vein thrombosis is there still uncertainty about the need to occasionally rely on venography. Radiologists must become cognizant of the capabilities of ultrasonography and facile in its interpretation. Performance of this test should be available in every institution. The nonradiological literature is replete with articles documenting the use of venous ultrasonography and encouraging its routine use for venous clot evaluation. PMID- 1736376 TI - Basic principles and clinical applications of magnetic resonance angiography. PMID- 1736377 TI - Doppler principles. PMID- 1736378 TI - The role of the vascular laboratory in clinical decision-making. PMID- 1736379 TI - When to save the ruptured spleen. PMID- 1736380 TI - Selected management of pancreatic pseudocysts: operative versus expectant management. AB - BACKGROUND: The aim of this study was to determine if nonoperative, noninterventional expectant management of pancreatic pseudocysts is warranted in selected patients. METHODS: From 1980 to 1985, 114 patients with the diagnosis of pancreatic pseudocyst were evaluated. RESULTS: Forty-six patients underwent primary operative therapy, with 13% undergoing emergency operations for pseudocyst-related complications. Although no operative deaths occurred, significant morbidity occurred in 26% of patients (emergency operations, 67%; elective procedures, 10%). The remaining 68 patients were initially treated selectively with a nonoperative, expectant approach. Severe, life-threatening complications in this group followed up for a mean of 46 months occurred in only 6 patients (9%); 19 patients eventually underwent elective operation directed at either the pseudocyst or other complications related to pancreatitis. Overall, in patients managed by a nonoperative approach, resolution of the pseudocyst occurred in 57% of the 24 patients with satisfactory radiographic follow-up, with 38% resolving more than 6 months after diagnosis. Although patients eventually undergoing operation tended to have larger pancreatic pseudocysts than the patients managed successfully nonoperatively (6.9 vs 4.9 cm), no serious complications occurred in seven patients with pancreatic pseudocysts greater than 10 cm who were treated expectantly. CONCLUSIONS: A nonoperative, noninterventional, expectant approach is warranted in the management of selected patients with pancreatic pseudocysts. PMID- 1736381 TI - Long-term follow-up of children with colon and gastric tube interposition for esophageal atresia. AB - BACKGROUND: There are two major methods of esophageal substitution for children born with long-gap esophageal atresia. This study was undertaken to see whether one method of substitution emerged as clearly superior to the other. METHODS: Twenty-four UK children who received a colon transposition for esophageal atresia were compared with 15 US children with esophageal atresia who received a gastric tube. The charts of all patients were reviewed. Follow-up data were obtained by questionnaire, and more than 80% of patients were personally evaluated at follow up clinics. RESULTS: At follow-up US children were 3 1/2 to 18 1/2 years of age; UK children were 7 1/2 to 19 years of age. Most of the children fell at or below the 10th percentile for height and weight, reflecting the tendency for prematurity in infants with esophageal atresia. One half of the children needed to eat slowly and to avoid certain meats. Dysphagia was rare. Older children ate socially with their friends without embarrassment. Early complications were technical; there were few late complications, and no difference was apparent between the two groups. CONCLUSIONS: In subjects who were growing, no difference was noted between the two methods of substitution as far as nutrition, growth, patient acceptability, or complications, early or late. Both groups functioned well and appeared to improve with the passage of time. PMID- 1736382 TI - Nutritional status seven years after Roux-en-Y gastric bypass surgery. AB - BACKGROUND: Nutritional deficiencies in patients after Roux-en-Y gastric bypass operations have been mainly attributed to dietary restriction. However, most of these studies have been performed during the period of greatest caloric restriction. METHODS: Two hundred patients who were morbidly obese were followed for 6 to 8 years (mean, 6.7 years) after Roux-en-Y gastric bypass surgery. Each underwent a thorough physical examination and behavioral and nutritional assessments, including hemoglobin, red blood cell indices, serum iron content, iron binding capacity, and serum vitamin B12 and folic acid concentrations. RESULTS: Data obtained from blood tests disclosed a significant gradual decrease of the mean serum hemoglobin (p less than or equal to 0.0000), mean corpuscular volume (p less than 0.001), and iron saturation (p less than or equal to 0.0000). Mean vitamin B12 concentration improved during the last 3 years of follow-up. The mean values of iron saturation and vitamin B12 were not correlated with the patients' weight loss. Meat intolerance was observed in 51%, 60.3%, 59.5%, and 55.1% of the patients during the 0 to 12 months, 13 to 24 months, 25 to 72 months, and 73 to 96 months after surgery, respectively. A significant correlation was found between the eating habits and the laboratory values. The mean serum iron saturation, vitamin B12, and folic acid were significantly higher in patients who eat meat than in patients who do not eat meat (piron less than 0.0046, pB12 less than 0.0052, folate less than 0.01). In addition, oral vitamin and mineral supplements significantly improved the nutritional status of the patients. The patients had no caloric malnutrition or protein deficiency. CONCLUSIONS: Roux-en-Y gastric bypass induces long-term changes in eating habits, independent of caloric intake. Iron continuously declines 6 to 8 years after surgery, depending (significantly) on the eating behavior, but not on the caloric intake. PMID- 1736383 TI - Pacing the human stomach. AB - The aim of this study was to document the pattern of human gastric pacesetter potentials after abdominal operation and to determine whether the potentials could be paced by electrical stimuli. Ten patients undergoing cholecystectomy had temporary serosal electrodes positioned along the greater curvature of the stomach. Bipolar myoelectric recordings and attempts at electrical pacing were made after operation. On postoperative day 1, the pacesetter potentials had a regular frequency (3.2 +/- 0.1 cycles/min), and no gastric dysrhythmias were evident. The distal stomach of nine of ten patients could be entrained by pacing the proximal electrodes (forward pacing) to a maximal rate of 4.3 +/- 0.3 cycles/min (p less than 0.05 versus nonpacing) without a change in propagation velocity or direction. Backward pacing (maximum rate, 3.9 +/- 0.2 cycles/min) was possible in six patients. Forward pacing was successful by day 3 in only four of ten patients, and backward pacing was successful in none of ten patients. A meal given a median of 3.5 days after operation did not change the pacesetter potential frequency, rhythm, or direction of propagation, and three of ten patients had successful forward pacing after a meal. In conclusion, a regular pattern of gastric pacesetter potentials is present after cholecystectomy. The gastric pacesetter potentials can be paced with electrical stimuli, although refinements of the pacing electrodes or stimuli will be needed to achieve long term pacing. Pacing holds promise as a potential treatment for gastric myoelectrical disorders. PMID- 1736384 TI - Liver transplantation by "face-a-face" venacavaplasty. AB - A modification of the technique of liver transplantation by the face-a-face venacavaplasty is described and the use in four patients reported. This technique enables livers with a small vena cava to be inserted in an anatomic fashion and should help increase the use of such grafts where disparity between vessel size exists. PMID- 1736385 TI - Encephalo-omental synangiosis in the management of moyamoya disease. AB - Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by stenosis of the intracranial internal carotid artery often accompanied by stenosis of the anterior and/or middle cerebral arteries. This results in cerebral ischemia, which manifests clinically as transient, repetitive episodes of hemiplegia, dysarthria, and involuntary movements. This case report documents a patient in whom an initial extracranial-intracranial bypass (superficial temporal-middle cerebral artery) failed to alleviate the ischemic symptoms. In a subsequent procedure, a pedicle graft of omentum was created and through a subcutaneous tunnel was placed on the right cerebral cortex. Over a 2 1/2-year period, this has resulted in a dramatic resolution of the patient's symptomatology. The report delineates the condition and reviews other therapeutic options. PMID- 1736386 TI - Small vessel occlusion in acute acalculous cholecystitis. AB - Ischemia is one mechanism implicated in the pathogenesis of acute acalculous cholecystitis. Gallbladder specimen arteriography was performed to define the comparative status of cystic artery runoff in the macroscopically normal gallbladder (n = 10), in acute gallstone-associated cholecystitis (n = 10), and in acute acalculous cholecystitis (n = 7). Standardized film exposure and quantity of contrast medium administered permitted objective intergroup comparison. Compared to the macroscopically normal gallbladder, specimens of acute gallstone-associated cholecystitis exhibited arterial dilatation and extensive venous filling. In contrast, multiple arterial occlusions, with absent or minimal venous filling, were consistent features of acute acalculous cholecystitis; the degree of arteriographic abnormality for acute acalculous cholecystitis corresponded to the severity of gallbladder pathologic findings. Small vessel occlusion, on the basis of low splanchnic flow or intravascular coagulation, may be a fundamental element in the pathogenesis of acute acalculous cholecystitis. PMID- 1736387 TI - Xanthine oxidase: its role in the no-reflow phenomenon. AB - This study was designed to probe the hypothesis that oxygen-derived free radicals are involved in initiation of the no-reflow phenomenon. We developed a reproducible model of no reflow in the rat hind limb. Laser Doppler studies confirmed that the hind limbs perfused well after 2 or 4 hours of ischemia, but perfusion ceased in the first 10 minutes after 6 hours of ischemia. Venous blood samples and biopsy specimens of skin and muscle were taken after 2 and 4 hours of ischemia to study tissue injury. Blood samples were evaluated for xanthine oxidase (XO), xanthine dehydrogenase, and creatine phosphokinase (CPK) activities. Conjugated dienes and iodine 125-labeled albumin extravasation were quantified in tissue samples. Groups of animals were treated with inhibitors of XO (allopurinol), antioxidant enzymes (superoxide dismutase plus catalase), and free radical scavengers (dimethyl sulfoxide and dimethyl thiourea) to assess the roles of free radicals in ischemia-reperfusion injury in the hind limbs. After 4 hours of ischemia followed by reperfusion, plasma XO activity rose threefold over preischemia levels (p less than 0.05). Xanthine dehydrogenase activity did not change; conjugated diene levels in muscle rose twofold; CPK levels rose sixfold, and 125I albumin extravasation rose twofold (p less than 0.05). Pretreatment with the XO inhibitor allopurinol reduced XO activity to negligible levels and significantly attenuated conjugated diene levels, CPK levels, and albumin extravasation. Albumin extravasation was also significantly attenuated by pretreating animals with superoxide dismutase together with catalase, dimethyl thiourea, and dimethyl sulfoxide. In all animals pretreated with allopurinol or superoxide dismutase and catalase, reperfusion persisted after 6 hours of ischemia. These data suggest that, in ischemia followed by reperfusion, tissue injury is related to oxygen products derived from XO activity. PMID- 1736388 TI - Interferon-gamma attenuates hemorrhage-induced suppression of macrophage and splenocyte functions and decreases susceptibility to sepsis. AB - Although it is known that interferon-gamma synthesis and macrophage functions are depressed after hemorrhage, it remains to be determined whether systemic administration of interferon-gamma has any effect on hemorrhage-induced depression of macrophage and splenocyte functions. To study this, C3H/HEN mice were bled to a mean blood pressure of 35 mm Hg, maintained for 60 minutes, and followed by adequate fluid resuscitation. The mice then received either 1000 units interferon-gamma or saline solution (vehicle). Peritoneal (pM phi) and splenic (sM phi) macrophages and splenocytes were isolated 24 hours later. PM phi antigen presentation was measured by coculturing pM phi with the D10.G4.1 cell clone. Major histocompatibility complex class II (Ia) antigen expression was determined by direct immunofluorescence. Cytokine release by pM phi, sM phi, and splenocytes was assessed with specific bioassays. For survival studies, mice were subjected to sepsis 3 days after hemorrhage. Treatment with interferon-gamma restored (p less than or equal to 0.05) hemorrhage-induced suppression of pM phi antigen presentation capacity and Ia antigen expression and increased (p less than or equal to 0.05) interleukin-1 and tumor necrosis factor release by pM phi and sM phi, as well as splenocyte proliferation (p less than or equal to 0.05). Interferon-gamma also decreased (p less than or equal to 0.007) the susceptibility to sepsis after hemorrhage. Thus interferon-gamma represents a potent agent for treating hemorrhagic shock-induced immunosuppression and for increasing the ability of the host defense system to combat bacterial infections after hemorrhage. PMID- 1736389 TI - Effect of nutritional status on organic anion clearance by the swine liver. AB - Hepatic dysfunction follows a wide range of insults. Impaired excretion of organic dyes such as bilirubin often occurs before other obvious clinical defects in metabolic processes. Indocyanine green (ICG) is excreted through pathways similar to those of bilirubin. To determine the effectiveness of ICG as a marker of hepatic dysfunction related to clinical malnutrition, pigs received 5 mg/kg ICG with simultaneous sampling from the hepatic vein, pulmonary artery, and aorta over 3 hours. Group I remained well nourished, group II was fasted to a weight loss equal to 20% of initial body weight, and group III was fasted to a 20% weight loss and then refed until the animals regained their initial weight. Both systemic and intrinsic hepatic clearance were depressed significantly with fasting but returned above baseline after refeeding. No significant difference appeared between systemic and intrinsic hepatic clearance. Extraction ratios were low in all groups. In outbred swine, ICG clearance reflects the function of hepatic organic anion excretion in vivo, and venous sampling reflects intrinsic hepatic clearance. The impairment of the carrier-mediated transport system is reversible with refeeding. PMID- 1736390 TI - The value of hepatic artery reconstruction as a technique in rat liver transplantation. AB - The importance of hepatic artery reconstruction in the success of liver transplantation in the rat has been studied. Rat liver grafts were performed with or without reanastomosis of the hepatic artery, both in rejector and nonrejector donor/recipient combinations. No significant improvement in recipient survival was found when arterialization was performed, and histologic studies showed no differences in hepatocyte or bile duct architecture between arterialized and nonarterialized groups. Thus, arterialization does not make an important contribution to the outcome of liver transplantation in the rat; biliary complications associated with the nonarterialized method appear to be technique related rather than the result of ischemia. PMID- 1736391 TI - Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. AB - Postoperative serum interleukin-6 (SIL-6) and C-reactive protein (SCRP) levels were examined in 71 patients who underwent various types of abdominal surgery. Similar time-dependent changes in SIL-6 and SCRP levels were observed in 12 patients despite differences in surgical procedures and liver function among the patients. SIL-6 started to increase within 3 hours after the beginning of the operation and reached a peak after 24 hours. SCRP started to increase after 12 hours and was maximum at 48 to 72 hours. The increase in SIL-6 at 24 hours (delta IL-6) showed a close correlation with that of SCRP at 48 hours (delta CRP) in 53 patients without liver cirrhosis. In 18 patients with liver cirrhosis, delta CRP relative to delta IL-6 was less than that in patients without cirrhosis and was poorly correlated with the latter. delta IL-6 was correlated with the length of time of the operation and blood loss in both groups, but delta CRP showed no significant correlation with these factors in either group. These findings indicate that the increase in IL-6 triggered by a surgical procedure may function as a hepatocyte-stimulating factor and that monitoring of SIL-6 may be more helpful than monitoring of SCRP for estimation of inflammatory status and early detection of an acute-phase response. PMID- 1736392 TI - End-to-end anastomosis between a prosthesis and a vein of different diameters: a technique that maintains a straight vascular axis. AB - In a composite femoropopliteal bypass, the intermediate anastomosis between a vascular prosthesis and the available vein is often difficult to carry out because of a discrepancy of the diameter between the two vessels. The end-to-end anastomosis is performed by working with the elasticity of the venous tissue resulting in anastomotic kinking. A technique keeping the vascular axis straight between two vessels of different diameters and elasticity is presented. PMID- 1736393 TI - Colon invasion by primary splenic lymphoma: a case report and review of the literature. AB - Primary splenic lymphoma accounts for 1% of lymphomas. The definition of primary splenic lymphoma is controversial and its clinical presentation is variable. This report describes a patient with primary non-Hodgkin's lymphoma of the spleen with transmural colonic invasion. This unique case represents the first reported instance of splenic lymphoma with histologically demonstrated invasion to the colonic mucosa. The clinical and pathologic features of this case and primary splenic lymphoma in general are reviewed. PMID- 1736394 TI - Pneumoperitoneum and signs of peritonitis from a pleuroperitoneal shunt. AB - Pleuroperitoneal shunting has become an increasingly popular therapeutic option for the control of intractable pleural effusions. However, there exists a paucity of information regarding institutional and individual experiences with this technique. We report an unusual complication of a Denver pleuroperitoneal shunt that resulted in pneumoperitoneum and a clinical picture of diffuse peritonitis from a ruptured abdominal viscus. The cause of this condition was continuous decompression of a pneumothorax into the peritoneal cavity, through the shunt. PMID- 1736395 TI - Normocalcemia thirteen years after successful parathyroid allografting in a recipient of a renal transplant. AB - Two months after receiving a cadaveric renal allograft, a 36-year-old woman received a parathyroid allograft from a living unrelated donor, who was haploidentical to the renal donor. Her preoperative 24-hour urinary excretion of calcium was 0.18 gm/24 hrs, and after operation it decreased to 0.004 gm/24 hrs, (normal, less than 0.20 gm/24 hrs). The C-terminal parathyroid hormone level increased from 155 pg/ml (normal, 275 to 675 pg/ml) to 327 pg/ml after operation. The N-terminal parathyroid hormone level in her grafted arm has varied between 2.5 to 10 times the level in her nongrafted arm. Thirteen years later, both allografts are functioning normally. To our knowledge, this is the longest functioning parathyroid allograft. PMID- 1736396 TI - Management of common bile duct obstruction associated with spontaneous perforation of the biliary tree. AB - Spontaneous perforation of the extrahepatic biliary tree during infancy is an uncommon event. The cause of bile duct perforation is unclear, but one-quarter of reported cases have been associated with a stone or bile sludge obstructing the distal common bile duct. A 4-week-old girl had jaundice, and a DISIDA (99m technetium diisopropyl iminodiacetic acid) scan revealed perforation of the biliary tree. Exploratory surgery showed distal common bile duct obstruction with proximal perforation. No attempt was made to remove the obstructing lesion because of duct inflammation. Common bile duct obstruction persisted until week 5 after surgery when cholangiography revealed free flow of contrast into the duodenum through a common bile duct of normal caliber without a filling defect. In the presence of acute inflammation associated with perforation of the biliary tree, exploration of the common bile duct to relieve a distal obstruction could prove hazardous. Our case and a review of the literature suggest that the obstructing stone or sludge may pass spontaneously if managed expectantly. PMID- 1736397 TI - [Acute epididymitis or testicular torsion?--the differential diagnosis is not always simple]. AB - Torsion of the spermatic cord continues to be a diagnostic dilemma. All lesions suspicious for torsion should therefore be explored. Acute epididymitis can nowadays more often be treated based on microbiological results. In most children and many elderly pathological findings in the lower urinary tract have to be evaluated and treated. PMID- 1736398 TI - [Practical advice for the care of patients with indwelling bladder catheters]. AB - Catheterizing a patient, whether short or long term, was once defined as a simple task, but it is not without complications (infection, calcification, and urethral stenosis). The author makes several recommendations for the care of patients with indwelling catheters. PMID- 1736399 TI - [Suprapubic urinary diversion using Cystofix--an alternative to the urethral indwelling catheter]. AB - Suprapubic Cystofix-cystostomy is a valuable alternative to the Foley-catheter. The advantages of suprapubic cystostomy are mainly a reduction of urinary tract infections, inflammatory reactions in the lower urinary tract and avoidance of late urethral strictures after transurethral catheterism. There are a few contraindications to be considered, mainly an empty bladder and coagulation disorders. The complication rate of suprapubic Cystofix-cystostomy, usually gross haematuria, is very low. Cystofix-cystostomy is as useful for short term urinary drainage as for long term drainage in the case of chronic voiding disorders. PMID- 1736400 TI - [Biopsy of the testis]. AB - Biopsy of the testis has been considered for a long time and continues to be an acknowledged method of examination in the framework of investigation of male infertility. A classical indication for this is the repeated statement of azoospermia with normal size of the testes. On part of the spermogram, the indication for testicular biopsy is however not limited just to azoospermia. On the other hand, one can do without a biopsy when the size of the testes is less than 2.5 cm, as almost certainly a pronounced testicular atrophy which cannot be influenced will be present. Diagnosis of testicular precancerous conditions represents a more recent indication for biopsy of the testis which will probably gain more importance in the future. Anamnestic and clinical informations and above all the correct fixation and treatment of the specimen are an absolute prerequisite for the perfect interpretation of the bioptic picture. PMID- 1736401 TI - [Preventive measures in stones due to infection, uric acid and cystine]. AB - General prophylaxis of renal stone formation consists of 1. high fluid intake and 2. modest consumption of protein-rich foods. Specific prophylactic measures are based on pathophysiologic mechanisms of stone formation. In infection-induced renal stones, combined treatment with culture specific antibiotics and complete stone removal is of utmost importance. In all cases where stone fragments cannot be removed completely and/or partial obstruction remains, long-term antibiotics in combination with urine acidification by methionine (urine pH 5.6 to 6.2) are most appropriate. Prophylaxis of uric acid stones primarily consists of reducing purine intake and alkalizing the urine by potassium citrate. Only if this regimen failed or gout occurred, allopurinol should be administered. In patients with cystine stones, urine volume should be increased to greater than 3000 ml/die. Alkalizing the urine to a pH greater than 7.5 rises cystine solubility, whereas cystine excretion may be reduced by a diet low in sodium and/or low in methionine/cysteine. Thiols form mixed thiol-cysteine disulfides that are many times more soluble than cystine in urine; because of their high rate of adverse side-effects, however, these compounds are of lowest priority in the treatment of cystine stones. There is no convincing evidence for the efficacy of high dose ascorbic acid treatment in cystinuria. PMID- 1736402 TI - [Intracavernous self-injection in impotence]. AB - On the basis of new diagnostic methods, 50 to 80% of impotent men show organic changes which are potentially responsible for erectile dysfunction. In our institution 409 consecutive patients have been submitted to the programme of intracavernous self-injection of papaverine. In 11% of the patients erectile function was normalized after a series of self-injections. 25% use papaverine regularly at home, and 64% discontinued the self-injections. Many of these patients did not accept this form of therapy. Side effects are rare and harmless. Early information about the intracavernous self-injection therapy by the physician can help to avoid unnecessary investigations. PMID- 1736403 TI - [Surgical refertilization following vasectomy--an increasing need]. AB - Surgical refertilization by vaso-vasostomy, taking place a long time after vasectomy, gains increasing importance in men whose partnership condition has changed since the time of sterilization. Apart from the surgical technique, the length of time between vasectomy and vaso-vasostomy, the age of the patient and immunological factors are of importance for the success of the vaso-vasostomy, that is the procreation of sound children. From the view of the surgical technique the single-layered anastomosis without splinting, carried out with magnifying glasses, produces satisfactory results comparable to those of more complicated techniques (operation microscope). The success rate of recanalization is between 80 and 95%. However, the rate of refertilization (ejaculation of fertile sperms) is between 50 and 70% only. Firstly, this discrepancy is based on the space of time between vasectomy and vaso-vasostomy. If the vasectomy has taken place more than ten years ago, the prognosis is significantly poorer. Secondly, it is based on the occurrence of circulating sperm antibodies after vasectomy. This rare immunological phenomenon, which is based on a disturbed resorption of sperms, reduces the fertility considerably. Thirdly, the age of the patient is of importance. If the patient is more than 50 years old at the time of surgery, the fertility is significantly reduced, as the spermatogenesis deteriorates in this age group under normal conditions as well. In spite of these reservations the surgical refertilization after vasectomy by means of vasovasostomy is a promising method, that can be recommended to the patient concerned. PMID- 1736404 TI - [Hematuria and diagnostic procedures]. AB - In the past ten years the strategies for evaluation of hematuria seem to have quite changed. Lately published articles show diverging opinion especially concerning the value of IVP and sonography. We propose an evaluation procedure with regard to the practitioner and the everyday routine using urinalysis including search for dysmorphic erythrocytes and cytology, sonography, IVP and cystourethroscopy for screening. Sonography and IVP are in our opinion complementary tests regarding accuracy of screening the renal parenchyma and the urothelial channel respectively. and the urothelial channel respectively. Other tests are used only specifically for detailed information about pathological findings during evaluation. PMID- 1736405 TI - [Hormones and mammary tumors in the bitch: a review]. AB - Toxicity studies as well as epidemiological studies in veterinary medicine have shown that both ovarian steroids and a large number of synthetic derivatives may promote the formation of mammary tumours in dogs. Abnormalities in pituitary function, particularly in the secretion of growth hormones, have been assumed to be involved in this process. In the present paper the possible role of endogenous and exogenous hormones in the pathogenesis of mammary tumours in bitches is reviewed. The available evidence suggests that steroid hormones may act at an early stage in the development of tumours by stimulating the proliferation of normal epithelium. This results in an increase in the number of susceptible cells. In addition a growth-stimulating action may be exerted upon cells which have undergone partial malignant transformation, but possibly to a lesser extent upon fully malignant cells at a late stage of tumour development. In advanced mammary cancers steroid receptors are frequently absent, which may indicate a more autonomous pattern of growth. It seems justified to conclude that in clinical practice ovariectomy at an early age as a measure to prevent oestrus is to be preferred to progestin treatment with regard to the risk of mammary carcinoma. Still, there is no indication that in dogs, ovariectomy will reduce the risk of metastasis once the animal is presented with a mammary carcinoma. The earlier assumption that overproduction of growth hormone is an important factor in the pathogenesis of spontaneous mammary tumours in the dogs could not be proven. The role of prolactin and of thyroid hormones in this process continues to be uncertain. PMID- 1736407 TI - [Necropsy findings in fattening pigs during the period 1979-1989]. AB - Necropsy findings of 1041 fattening pigs, during the period of 1979-1989 are presented. The pigs originated from one veterinary practice association. Enterotoxicosis associated with E. coli serotype O149:K91:K88 was the most prevalent diagnosis, followed by fibrinous pleuropneumonia due to Actinobacillus pleuropneumoniae. A decrease was noticed for Aujeszky disease during the late years. After 1985 an increase was found for torsio mesenterialis. In 1.7% of the cases no post mortem diagnosis could be made. PMID- 1736406 TI - [Lead poisoning in cattle in Northern Netherlands. Follow-up study of 2 farms]. AB - The after-effects of a serious lead intoxication were studied. This intoxication was caused by contaminated feed. Calves and cows of two dairy farms were examined up to half a year after the incident with the contaminated feed in October 1989. Clinical signs were observed and blood samples were taken. Blood parameters like zinc-protoporphyrin (ZPP), haemoglobin, RBC, WBC, MCV, haematocrit, MCHC, and the blood lead levels were analysed. Cattle of one of the most afflicted farms showed severe effects of lead intoxication: blindness, muscle twitching and hyperirritability. Two animals died. Forty percent of the affected cows had to be slaughtered. The ZPP levels in calves of this farm were still elevated after six months. The zinc-protoporphyrin level in blood seemed to coincide better with the clinical signs than the blood lead level. Animals with less than 3 mg ZPP/l RBC showed no irreversible effects of the lead intoxication. It is suggested that ZPP could be a useful predictor for the after-effects of lead intoxication. PMID- 1736408 TI - [Aspiration pneumonia]. PMID- 1736409 TI - [Once again: patellar dislocation]. PMID- 1736410 TI - [Euthanasia]. PMID- 1736411 TI - [12 years control of hog cholera in the EEC]. PMID- 1736412 TI - Altered distribution of 109cadmium in mice during viral infection. AB - The distribution of the toxic heavy metal cadmium (Cd) was studied in Coxsackie virus B3 (CB3)-infected Balb/c mice by whole-body autoradiography and gamma counting. The distribution of 109Cd was studied 4 days post CB3-inoculation and 10 min after intravenous injection of 0.21 microgram of Cd/kg body weight. Whole body autoradiography results showed that the distribution of 109Cd is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the renal and adrenal cortices. After impulse counting of selected organs it was found that the normal accumulation of 109Cd in the kidneys (184,354 +/- 30,961 c.p.m.) was increased by 47% (P less than 0.05) during CB3 infection (270,503 +/- 54,780 c.p.m.). In contrast to healthy animals, some infected mice showed accumulation of 109Cd in the spleen. These results show for the first time that an invading micro-organism can change the distribution of an environmental pollutant. PMID- 1736413 TI - Cellular localization and hormonal regulation of 7,12-dimethylbenz[a]anthracene mono-oxygenase activity in the rat ovary. AB - To identify the ovarian cell type(s) responsible for the metabolism of 7,12 dimethylbenz[a]anthracene (DMBA) and their dependence on hormonal influences, DMBA mono-oxygenase activity was determined in primary cultures of cells dispersed from rat ovaries and separated by centrifugation on discontinuous Percoll density gradients. The contents of progesterone and oestradiol in the different cell cultures were characterized. Moreover, the morphological appearance of ovarian cells obtained from untreated and pregnant mare's serum gonadotropin (PMSG)-treated rats was examined. It is concluded from experiments with immature PMSG-treated rats, that DMBA mono-oxygenase activity is localized in follicular granulosa (and/or theca) cells. This activity decreases during luteinization, and is recovered in a population of cells harvested at a higher density on the Percoll gradient. The xenobiotic-metabolizing activity was not correlated to the rate of biosynthesis of progesterone or oestradiol in isolated cells, measured in the presence or absence of human chorionic gonadotropin and/or testosterone. However, a certain dependence of DMBA metabolism on steroids and/or steroid-synthesizing enzymes could not be excluded. For example, DMBA mono oxygenase activity was markedly increased in a cell population, tentatively identified as granulosa cells, obtained from untreated mature rat ovaries upon addition of testosterone, which is the substrate for oestrogen synthesis, to the cell culture. PMID- 1736414 TI - Alteration in surface structure of Clara cells and pulmonary cytochrome P-450b level in rats exposed to ozone. AB - Changes in the surface structure of Clara cells in the terminal bronchioles following exposure of rats to 0.4 ppm ozone (O3) for 14 days were evaluated and compared to the content of pulmonary cytochrome P-450, an enzyme active in xenobiotic metabolism. Exposure to O3 caused a striking alteration of Clara cells in the terminal bronchiole. After 6 h exposure apical protrusions of Clara cells enlarged and these Clara cells formed clusters. However after 24 h exposure, the Clara cells decreased in number and flattened. They increased in number and enlarged again during the subsequent period of exposure. By the 14th day of O3 exposure the number of Clara cells had increased significantly. The content of cytochrome P-450b (IIB1), a main isozyme of pulmonary cytochromes P-450 of rats, was determined by an immuno-blotting method using anti-cytochrome P-450b antibody. The cytochrome P-450b in the rats exposed to O3 increased significantly to 1.37- and 1.81-times that of the control on the 7th and 14th days, respectively. Immuno-electron microscopy demonstrated that cytochrome P-450b was localized abundantly in endoplasmic reticulum of Clara cells. Morphological alterations in Clara cells appear to be closely related with changes in the cytochrome P-450b content of the lung. PMID- 1736415 TI - Comparative tumor-initiating ability of 7H-dibenzo(c,g)carbazole and dibenz(a,j)acridine in mouse skin. AB - N-heterocyclic aromatics are environmentally important carcinogenic pollutants produced by incomplete combustion of organic material. 7H-Dibenzo-(c,g)carbazole (DBC), is a potent skin and systemic carcinogen, whereas dibenz(a,j)acridine (DBA), is a carcinogen with local effects. Therefore, the overall objective of these studies was to determine the initiating ability of DBC and DBA in mouse skin using an initiation-promotion protocol. Acetone-, TPA- or BaP-treated animals were used as negative and positive controls, respectively. DBC, DBA or BaP (200 nmol) dissolved in acetone was applied once to the backs of thirty shaved Hsd:(ICR)Br female mice, followed 2 weeks later with 2 micrograms of TPA in 50 microliters of acetone applied twice a week for up to 24 weeks. Skin tumors developed in 26, 17 and 27 animals, respectively. DBC plus TPA produced a significant influx of dermal macrophages similar to that seen for BaP. Initiation with BaP, DBC or DBA moderated the effect of TPA on most other dermal parameters, particularly neutrophils. These data indicate that, DBC, with apparently different activation pathways than BaP shows similar tumor initiating ability and morphological changes as BaP. PMID- 1736416 TI - Contribution of acetone and osmotic-diuresis by streptozotocin-induced diabetes in attenuation of cephaloridine nephrotoxicity. AB - Previous studies have indicated that cephaloridine nephrotoxicity was reduced in streptozotocin (STZ)-induced diabetic rats. Experiments were performed to investigate if a shorter duration of diabetes would reduce cephaloridine nephrotoxicity. Studies were also conducted to examine the contribution of osmotic diuresis and ketone accumulation to the mechanism for reduced toxicity. Male Fischer 344 (F344) rats were injected with 30 mg/kg STZ or vehicle. Seven days after STZ or vehicle administration, the animals were treated (i.p.) with 1500 mg/kg cephaloridine. Increased kidney weight, blood urea nitrogen (BUN) level and decreased renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethyl-ammonium (TEA) were measured in the normoglycemic group. No differences in renal function were detected between diabetic groups treated with cephaloridine or vehicle (PFC). Pretreatment of euglycemic rats with 0 or 10% dextrose in the drinking water and by oral gavage failed to prevent the renal damage produced by 1500 mg/kg cephaloridine despite glucosuria and urine output comparable to diabetic animals. However, dextrose-diuresis afforded a slight reduction in toxicity as indicated by changes in kidney weight and renal cortical slice accumulation of PAH and TEA. Pretreatment (oral) with 0 or 1.5 ml/kg acetone had no effect on cephaloridine toxicity (1000 mg/kg, i.p.). These findings suggested that attenuation of cephaloridine toxicity may be independent of the duration of diabetes. These results also indicated that glucose-mediated osmotic diuresis and acetone accumulation cannot account for reduced cephaloridine toxicity in diabetic rats. PMID- 1736417 TI - Placental aryl hydrocarbon hydroxylase activity and placental calcifications. AB - Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal exposure to polycyclic aromatic hydrocarbons contained in cigarette smoke has been well documented. Furthermore, calcifications are more prevalent in the placentas of pregnant smokers than in those of non-smokers. The present study examines whether this latter relationship could be explained by the induction of AHH activity in the placenta. AHH levels were determined at birth in 141 unselected pregnant women admitted for delivery. Macroscopic placental examination was performed for vascular lesions, abnormalities of placental shape, of the cord and parameters of placental maturity such as basal and parenchymatous calcifications. Significant increases in the prevalence of calcifications of the placental basal plates and parenchyma with the induction of placental AHH were found. A similar significant association between smoking and AHH activation was also observed. These findings remained unchanged when controlling for smoking status assessed both by questionnaire and presence of cotinine in mother's urine. Moreover, the apparent association between smoking 'factor' and calcifications disappeared when controlling for AHH induction. Therefore, the association between smoking and placental calcifications previously related could be mediated by the AHH induction. PMID- 1736418 TI - Effect of cadmium on the monolayer maintenance of vascular endothelial cells in culture. AB - We investigated the effect of cadmium on the maintenance of the monolayer of vascular endothelial cells to clarify a possible involvement of endothelium injury in cadmium-induced vascular disorders. Endothelial cells from bovine aorta were cultured with cadmium chloride (0.5, 1.0, 2.0 or 5.0 microM) for 24 or 72 h. A histological observation revealed that a de-endothelialized space was formed in the monolayer by cadmium treatment; the number of endothelial cells was significantly decreased by the metal. Cadmium significantly decreased the number of growing endothelial cells with a significant decrease in the [3H]thymidine incorporation, suggesting that cadmium inhibited the cell proliferation. On the other hand, cadmium significantly increased the detachment of [3H]thymidine labeled endothelial cells from the monolayer with a parallel increase in the lactate dehydrogenase activity in the medium. From these results, it was suggested that cadmium impairs the endothelial cell monolayer; the de endothelialized space was formed by both an increase in the cell detachment by cadmium cytotoxicity and a retardation of the repair of the space which was due to an inhibition of the cell proliferation caused by the metal. PMID- 1736419 TI - Protective effect of NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L ornithine) against cyanide-induced convulsions in mice. AB - The effects of NG-nitro-L-arginine (NNA; an inhibitor of the oxidative L-arginine pathway) on convulsions induced by cyanide were investigated in mice. NNA prevented cyanide-induced convulsions in a dose-dependent manner. Furthermore, the inhibitory effect against convulsions induced by cyanide with NNA was abolished by pretreatment of L-arginine. However, NNA did not change blood cyanide levels in mice 5 min after injection of potassium cyanide. Since NNA prevents against oxidative L-arginine pathway-dependent guanylate cyclase activation in intact cells, it was suggested that the protection against cyanide induced convulsions with NNA may be due to the inhibition of guanylate cyclase. In support, methylene blue, an inhibitor of guanylate cyclase, elicited a similar inhibition against convulsions induced by cyanide. PMID- 1736420 TI - Long-term results of knee synovectomy in pigmented villonodular synovitis. AB - 1. Pigmented villonodular synovitis (PVS) commonly affects the knee as a monoarticular proliferative process. The etiology is not understood. 2. Partial synovectomy for localized PVS and wide synovectomy for diffuse PVS institute a favorable result, despite a rather high rate of recurrence at long-term follow up. 3. Cases that involve bony erosion have a low incidence of recurrence but present an unsatisfactory prognosis even after curettage and wide synovectomy (postoperative progress of osteoarthritic changes). PMID- 1736421 TI - Honesty: the best policy in nursing practice. AB - 1. In the process of delivering patient care, nurses are constantly faced with choices of actions that can be either honest or dishonest. Dishonesty may be selected out of a desire to protect oneself, the patient, or even the doctor. 2. Although nurses must often choose between being honest and dishonest, being dishonest violates the trust placed in the nurse and undermines the nursing profession; dishonesty is never justified. 3. To err and to not set the record straight is dishonest and leads to lack of self-respect, lack of respect from others, lack of trust from patients and coworkers, lack of credibility, patient harm, and occasionally to lawsuits. PMID- 1736423 TI - Don't recap those needles! PMID- 1736422 TI - When patients die in the operating room. PMID- 1736424 TI - The changing role of the pediatric OR nurse. AB - 1. OR nurses are trained to listen, observe, and pass the necessary instrumentation. On their road to gain professional status, they must not forget the need to improve clinical and professional skills as well as why they went into nursing: patient care. 2. Many OR nurses do not try to eliminate fears, no matter what the age of their patients, and some may have even added to patient fears. Although such nurses are the exception, OR nurses should strive to keep themselves from being classified as uncaring. 3. Preoperative tours and postoperative visits should become an essential part of the surgical experience. Ideas and concerns should be addressed, and changes to enhance future surgical procedures should be discussed. PMID- 1736425 TI - Perioperative care of the craniotomy patient: a review. AB - 1. Knowledge of the patient and the planned positioning allows the perioperative nurse to prepare for the needs of the individual craniotomy patient in surgery. 2. Microsurgical instrumentation often required with a craniotomy requires special handling and care. 3. Methylene blue should never be used in neurosurgical procedures. 4. The sitting position for posterior fossa surgery requires special precautions. PMID- 1736426 TI - [Dementia research in Denmark]. PMID- 1736427 TI - [The social breakdown in senile dementia and physician's role]. PMID- 1736428 TI - [The admission and discharge patterns of patients with dementia in psychiatric hospitals]. AB - This paper describes the admission and discharge pattern in a psychiatric hospital for 315 senile and arteriosclerotic demented patients (290.09, 293.09 ICD-8) aged 65 years and over and admitted for the first time. 47% (149) of the patients were admitted from other hospitals and temporary stays in nursing homes. A total of 203 (65%) of the patients experienced one or more changes of residence during the three months prior to admission to the psychiatric hospital. A Kaplan Meier analysis showed that 25% of the patients were still hospitalized 48 weeks after admission. A total of 62 patients died in the psychiatric hospital, one patient was still hospitalized when the investigation ceased. Of those discharged alive 201, (80%) were discharged to nursing homes 26 (10%) to their own homes and 25 (10%) to hospitals. Of those who had their own home at the time of admission and were discharged alive only 16% were discharged to their own homes, the remainder were discharged to nursing homes and hospitals. On account of the many changes of environment the demented patients experience prior to admission to the psychiatric hospital, they risk developing confusional psychoses which may be disastrous to their physical and mental health. PMID- 1736429 TI - [Use of psychopharmaceuticals and commitment in psychiatric admissions of elderly patients with dementia]. AB - Case records of 404 elderly patients (aged 65 years or more) who were admitted for the first time to the Psychiatric Hospital in Aarhus were investigated retrospectively. In 315 patients the diagnoses were senile dementia (290.09) and arteriosclerotic dementia (293.09) according to ICD-8. Information about use of psychotropic drugs before admission and on discharge alive was obtained from the patient case records. In the present study, the use of drugs was not found to be correlated with age, sex and degree of dementia. Significantly fewer committed patients were treated with psychoactive drugs and significantly fewer lived independently in their own homes. Only 42 (13%) patients had a crude psychiatric disorder while 251 (80%) were admitted on account of unacceptable behaviour. 90% of the latter group of patients had been treated with one or more psychoactive drugs on admission. The risks involved in the use of psychoactive drugs are discussed. On account of demographic changes in the Danish population and the recent decrease in psychiatric hospital beds and nursing home beds, it is recommended that the patterns of committed admissions of demented patients to psychiatric hospitals should be followed closely. PMID- 1736430 TI - [Shunt-nephritis]. AB - Infection in ventriculo-atrial shunts implanted for relief of raised intracranial pressure may, in rare cases, result in glomerulonephritis (shunt-nephritis). Most frequently, infection with low-virulent bacteria is concerned. This results in mild or subclinical symptoms with the subsequent risk that the condition is overlooked. The glomerular damage is considered to be precipitated by deposition of immune complexes in the kidneys and subsequent activation of the complement system. The renal manifestations consist of varying degrees of proteinuria, haematuria and reduction of renal function. Treatment consists of removal of the shunt. If continued relief of pressure in the ventricular system is necessary, a ventriculo-peritoneal shunt should be implanted. Normally, the prognosis of the renal disease is good. If the diagnosis and treatment are delayed, irreversible renal damage may result. Regular control of urine (proteinuria, haematuria) and blood (Hb, serumcreatinine and serum complement) are recommended in the follow up control of patients with ventriculo-atrial shunts. PMID- 1736431 TI - [Septic sacroiliitis]. AB - Septic sacroiliitis (SSI) is a rare form of pyogenic arthritis, which unrecognized or inadequately treated may cause longterm morbidity and eventually lasting disability. SSI is most frequently diagnosed among young adults, especially in drug abusers. Based on a literature survey three cases of SSI are presented, each representing characteristic aspects of SSI. The condition should be considered in cases of acute or subacute onset of pain in the gluteal region, hip or low back accompanied by fever. Laboratory findings are variable and non specific. Definite bacteriologic diagnosis is only achieved in about 75% of the cases. In almost all of the cases, Tc-99m-MDP bone scintigraphy will in almost all the cases show increased uptake in the affected joint within one week after onset of symptoms. Generally antibiotic treatment leads to complete recovery. PMID- 1736432 TI - [201-thallium myocardial scintigraphy before and after percutaneous transluminal coronary angioplasty]. AB - We describe our experience from the first 30 patients treated with percutaneous transluminal coronary angioplasty (PTCA) in the Cardiologic Department P, Gentofte Hospital. The main purpose was to evaluate the value of thallium scintigraphy performed before and three months after PTCA. After PTCA, 23 (77%) had no angina and 22 (73%) had normal exercise-ECG. On the basis of the scintigraphies before PTCA, the patients were divided into two groups: In group 1, five had normal scintigraphy and 14 reversible perfusion defects only. In group 2, all 11 patients had both persistent and reversible defects. In patients without persistent defects, significantly more were free from angina. No difference was observed between group 1 and 2 in percentage stenosis of the vessel or in reduction of the diameter. Significant reduction in the extent of reversible perfusion defects after PTCA was observed in both groups and also in the extent of persistent defects in group 2. In about 1/3 of the patients, the changes in percentage stenosis after PTCA and in the perfusion as judged by the scintigraphies differed. Therefore, as the two methods supplement each other, the main conclusions are: 1) Evaluation of the revascularization procedure is more reliable if a scintigraphy is obtained both before and after PTCA than if only coronary arteriography is performed. 2) Scintigraphy alone suffices for the three month follow-up examination, partly because it gives better information about the myocardial perfusion than does the arteriography, partly because scintigraphy is a noninvasive procedure. PMID- 1736433 TI - [Idiopathic interstitial pulmonary fibrosis. Clinical picture, diagnosis, treatment and prognosis]. AB - Idiopathic pulmonary fibrosis (IPF) was found to have a higher incidence than previously assumed and the population involved was younger. These findings were made in a retrospective investigation during the period 1986-1990. The condition should be suspected on the basis of the radiographic characteristics, reduced lung volume (TLC), decreased DLco during testing of pulmonary function, hypoxemia at rest and also the symptoms revealed in the medical history. It is of importance for planning of treatment that the diagnosis of IPF is confirmed early by excision biopsy of pulmonary tissue. Patients with IPF were treated successfully by intravenous administration of a solution of 500 mg methylprednisolone in 500 ml isotonic glucose. This regime is administered for three consecutive days and supplemented by azathioprine as required. In order to prevent further progression of this chronic disease, patients with IPF should be followed-up at frequent intervals. PMID- 1736434 TI - [Pyonephrosis on account of an ectopic ureterocele]. AB - A case of isolated pyonephrosis on account of an ectopic ureterocele in a thirteen-month-old boy without bacteriuria is presented. The importance of early diagnosis and treatment is emphasized. PMID- 1736435 TI - [Tendency to edema as the initial symptom of hyperthyroidism]. AB - Peripheral oedema which is not of cardiac origin may be an early clinical sign of hyperthyroidism. Measurement of the thyroid parameters is recommended in patients with sudden onset of oedema of the lower limbs and tachycardia without any immediate cause. PMID- 1736436 TI - [Discomfort once again]. PMID- 1736437 TI - [Nature products--advertising and acknowledgement]. PMID- 1736438 TI - [The forensic diagnosis: "chronic disease"]. PMID- 1736439 TI - [Hemophilia. Treatment of bleeders and the significance of their social situation]. PMID- 1736440 TI - [Social conditions of hemophiliacs]. AB - The objects of this investigation were 1. to describe the social conditions of haemophiliacs by means of questionnaires and to compare these with the population as a whole and 2. to investigate the social integration of haemophiliacs as assessed by type of family, occupation, club membership and contact with family and friends. The group investigated consisted of all Danish haemophiliacs with moderate to severe factor VIII and IX deficiency and cases of severe von Willebrand's disease. 64% replied (n = 135). Comparison by the age stratification with the population as a whole, showed that fewer haemophiliacs in the age group 25-44 years lived with partners and children and that more lived with their parents or alone. Haemophiliacs had a higher school education and more haemophiliacs were currently receiving occupational training. The occupational frequency was low for all age groups and more haemophiliacs had reduced working hours. The frequencies of contact with friends and family and access to practical assistance corresponded to that of the population as a whole. Social integration was correlated directly with school education and occupational training and satisfaction with contact with other people and inversely correlated with age, contact with social welfare offices and number of social payments received. Only a total of 6% of haemophiliacs were very poorly socially integrated. PMID- 1736441 TI - [Electric stimulation (ECT) in Parkinson disease]. AB - A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the treatment of Parkinson's disease with special reference to the therapy of "on-off" phenomena is given. The first report of positive effect appeared in 1959 and, with a single exception, all published articles on this topic point to a positive outcome of ECT. There seems to be a specific anti Parkinsonian effect alongside the well-known effect on various psychotic conditions. ECT thus must be considered a valuable intervention when drug therapy is insufficient, when prolonged medication leads to decreased efficacy, or when patients develop neuro-psychiatric manifestations. A short review of the pathophysiological mechanisms which may underly the effect of ECT in Parkinson's disease is given. PMID- 1736442 TI - [Magnesium and ischemic heart disease]. AB - Our knowledge about magnesium in health and disease has increased during the past ten years. Many authors have demonstrated possible magnesium depletion in the population as a whole and particularly among cardiac patients receiving diuretics. Evidence suggests that this magnesium depletion may play a role in the development of arteriosclerosis. It has been demonstrated that long term supplementation of the diet with magnesium reduces the frequency of heart disease. However, the matter is still not proven. It is postulated further that magnesium depletion aggravates the outcome of acute myocardial infarct and has a tendency to provoke arrhythmia. Finally, it has been shown that the potassium depletion frequently observed among cardiac patients may actually arise from magnesium depletion. On this basis, many authors have employed magnesium therapy in various cardiac diseases. Some authors have demonstrated that magnesium therapy reduces the mortality in AMI patients. These studies are, however, too few and too limited to be conclusive. In order to investigate this question, an international multicentre trial (ISIS-4) will be conducted to investigate the influence of magnesium therapy on the mortality after acute myocardial infarction. PMID- 1736443 TI - [Assessment of the diagnostic yield of cerebral CT in children]. AB - In order to show if an excessive use of cerebral computed tomography of children (aged 0 to 15 years) existed, scans from 157 patients from a single X-ray department was examined. The clinical information which was presented on referral of the patients was also investigated. No excessive use was proven, as 26.1% of the patients showed pathological changes on the scans. But the investigation also showed that the percentage could probably be higher if more (if not all) patients was examined by a neurologist before referral to the X-ray-department. PMID- 1736444 TI - [Ileus of the small intestine during the neonatal period. Treatment and prognosis]. AB - During 13 years, 47 infants were treated for mechanical ileus resulting from intestinal obstruction located proximally to the coecum (duodenal obstruction, malrotation, jejuno-ileal obstruction and meconium ileus). The mortality and morbidity were low. A total of three infants died; all of them in the immediate postoperative period. One infant died on account of rupture of the anastomosis; in two infants, death was caused by pulmonary complications and disseminated intravasal coagulation. Seven reoperations were performed and among these five infants on account of adhesions-/fibrous band ileus. At follow-up examination five infants were slightly underweight and retarded in growth; only one child had troublesome gastrointestinal problems. We recommend the use of antenatal ultrasound in the 30th week of gestation more frequently and always when polyhydramnios is present. This should raise the suspicion of gastrointestinal obstruction. Postnatal screening for associated congenital anomalies should also be done, since these are the most frequent cause of death in this patient category. PMID- 1736445 TI - [Monitoring of anesthesia during magnetic resonance imaging]. AB - Clinical employment of magnetic resonance scanning presents great diagnostic possibilities, partly in the form of the quality of the imaging and also on account of the possibilities for carrying out spectroscopic measurements by mens of which in vivo non-invasive chemical analysis of drug concentrations in the tissues may be performed. In anticipation of the possibility of employing MR scanning as an important diagnostic aid for assessing the causes of unconsciousness in patients in intensive care, attempts have been made to establish reliable and justifiable equipment for monitoring which can render possible investigation of unconscious or anaesthetized patients in scanners with magnetic fields of over 1.5 Tesla. The medical technical difficulties involved are mentioned and the solutions which are employed in the Danish scientific Centre for Magnetic Resonance in Hvidovre Hospital in Copenhagen are described. This monitoring includes continuous ECG recording, measurements of pulse and blood-pressure once per minute and continual monitoring of respiration including concentrations of carbon dioxide in the inspired and expired air and the concentration of oxygen in the inspired air. In addition, model solutions have be outlined for establishing mechanical ventilation with the servorespirator and the possibility of producing an employable pulse oxymeter is described. It is stated that, provided all of the elements in the above mentioned model solution for monitoring during anaesthesia in the MR laboratory have been carried out, it is considered justifiable to place all patients, including children, in the MR scanner. PMID- 1736446 TI - [Improved technique--improved diagnosis. An example from cytogenetics]. AB - The chromosomes of a severely retarded male with extreme kyphoscoliosis and obesity 20 years were reexamined by in situ hybridization of the centromere region. Partial trisomy 18 was revealed. PMID- 1736448 TI - [Legally induced abortions in 1990]. PMID- 1736449 TI - [Commitment as a substitute to nursing home care? A history about a precedent creating verdict according to the new psychiatric law]. PMID- 1736447 TI - [Bilateral epidural hematomas]. AB - Bilateral epidural haematomata are rare and comprise only approximately 2% of all the intracranial haematomata. The symptomatology frequently differs from that of unilateral haematomata in that lateralisation is frequently absent. Most commonly, protracted or secondary development of clouding of consciousness is encountered. In cases of head injury, the above mentioned symptoms are indications for emergency computed tomographic (CT) scanning. When operation is performed early, the prognosis is good. PMID- 1736450 TI - [Mammographic screening]. PMID- 1736451 TI - [Statistic mumbo-jumbo]. PMID- 1736452 TI - [Air moisturizing]. PMID- 1736454 TI - [Smoking cessation]. PMID- 1736453 TI - [Vaccination against yellow fever]. PMID- 1736455 TI - [Hypoglycemia in diabetes mellitus. Symptoms, epidemiology, physiopathology, causes and treatment]. AB - Hypoglycaemia is the commonest side effect of insulin treatment. The symptoms and occurrence of hypoglycaemia in patients with diabetes mellitus, treated or not treated with insulin, are reviewed. The hormonal and metabolic changes during insulin-induced hypoglycaemia in non-diabetics and causes of the defective counter-regulation in insulin-treated diabetic patients is found primarily in the defective insulin treatment available at present. The occurrence of hypoglycaemia may be reduced by improved understanding of the pathological physiology of insulin-treated diabetes mellitus and instruction of the patient. PMID- 1736456 TI - [A double-blind trial of nicotine patches in smoking cessation]. AB - The use of nicotine chewing gum combined with psychological support improves the success rate in stopping smoking. We studied the safety and efficacy of a transdermal nicotine patch in stopping smoking. We conducted a double-blind randomized study comparing the effect of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks. The rates of sustained abstinence were significantly better with active treatment than with the placebo: 53, 41, 24 and 17% of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5 and 4% of those in the placebo patch group (p less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch withdrew from the study because of side effects. The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with the placebo. PMID- 1736457 TI - [Impedance cardiography--non-invasive measurement of central hemodynamic data]. AB - The theory, method and apparatus behind a new computer technology for transthoracic electrical bioimpedance are described. Measurements and calculations of changes in the electrical conductivity of the thoracic segment during systolic upstroke provides the basis for non-invasive determination of stroke volume and cardiac output. Bioimpedance further offers a sensitive indicator of the content of thoracic fluid. Reports comparing measurements of cardiac output in various clinical conditions by bioimpedance versus invasive methods in general show good correlation. The field of applications and limitations of bioimpedance are described. Measurements are reproducible and the method can also be used in evaluating the cardiodynamic exercise response. PMID- 1736458 TI - [P-pills and risk of breast cancer. A review of studies published 1970-1990]. AB - A review of five cohort and 33 case-control studies provides evidence of an increased risk of breast cancer in women aged less than 45 years who were exposed to oral contraceptives for 5-10 years. It is probable that the increased risk is related to oral contraceptive use before the first pregnancy. No association was found between oral contraceptive use and breast cancer risk in women aged 45 years or more. PMID- 1736459 TI - [Information on AIDS among persons aged 16-20 years]. AB - In order to illustrate whether the AIDS and "Safe sex" campaigns have influenced young people, an investigation originally made in 1985 was repeated in October 1989; the objects being sexual knowledge, sexual experience and contraception among persons aged 16-20 years. A representative random sample consisting of 359 women (percentage replies 77.9) and 400 men (percentage replies 76.3) who were over 16 but not yet 21 years was interviewed personally by the professional interviewer staff of the Institute for Social Research. A total of 72% (n = 547) had been informed about AIDS at school, most of these were among the youngest participants. Simultaneously, 43% (n = 326) considered that school was the best source of information. School thus appears to be an effective channel of information about AIDS to young people. TV/radio were also found to be important channels of information while only few participants stated that they had received the best information in their homes. The majority of replies to questions about AIDS were in complete agreement with the messages in the informative campaigns. In conclusion, it is stated that the replies were markedly uniform without any obvious connection with sex, age, background or experience. Significantly more of the men, however, considered that their knowledge about AIDS was adequate. PMID- 1736460 TI - [Has the age at sexual debut changed after the Safe Sex Campaign?]. AB - In 1984, immediately before information about AIDS had reached the general public and the campaign for "Safe sex" had begun in earnest, 286 women (percentage replies 75.3) and 336 men (percentage replies 77.8) who were over 16 years but not yet 21 years were interviewed about sexual knowledge, sexual experience and contraception. In October 1989, the investigation was repeated and 359 women (percentage replies 77.9) and 400 men (percentage replies 76.3) participated. Both of the investigations were carried out as personal interviews by the professional interviewer staff of the Institute for Social Research. The age profiles for the first coitus were found to be practically identical in the two investigations. The median age for the first coitus was calculated to be 16.7 years in 1984 and 16.8 years in 1989 for females and 16.9 years for males in both 1984 and 1989. In both of the investigations, the majority stated that the first coitus was with a person of the same age group. Just under 1/4 of the women and nearly 1/3 of the men stated that the first coitus was also the first for the partner. In the 1989 investigation, significantly more stated that they had employed contraception at the first coitus. The campaign for "Safe sex" had recommended condoms. In the 1989 investigation, 61.0% of the women and 62.0% of the men had employed condoms at the first coitus as compared with 36.5% of the women and 42.1% of the men, five years previously. Parental advice about contraception had also changed as a great many more stated that their parents had advised them to use condoms as a contraceptive measure in the 1989 investigation. Among the young people who had not yet had coitus, 24.4% of the women and 34.7% of the men stated in 1989 that they always had a condom handy when they thought they might need it. PMID- 1736461 TI - [Pancreato-pleural fistula in a patient with chronic pancreatitis]. AB - A case with pancreaticopleural fistula formation in a 33-year-old man with alcohol-induced chronic pancreatitis with a pseudocyst in the head of the pancreas is reported. The patient was treated with repeated pleurocentesis, but the fistula first closed and was drained after treatment with the somatostatin analogue, sandostatin, for 38 days and total parenteral nutrition for 26 days probably because a spontaneous pancreaticogastric fistula had then formed. At the most recent outpatient control re-examination of the pancreas with ultrasound no cyst was shown. PMID- 1736462 TI - [Corkscrew esophagus]. AB - "Corkscrew oesophagus" is characterised on the basis of two case reports and attention is drawn to thoracic pain of oesophageal origin. Corkscrew oesophagus is a radiological diagnosis and is characterised by twisted segments in the distal third of the oesophagus. The condition can sometimes be demonstrated endoscopically and it is due to a basic disturbance in the motility of the oesophagus. Painful conditions in the oesophagus are most frequently caused by gastro-oesophageal reflux or disturbances in motility and the latter is frequently complicated by reflux oesophagitis. Pain of oesophageal origin is frequently a diagnosis by exclusion and requires exclusion of ischaemic heart disease. The initial treatment should be directed to the reflux oesophagitis. The diagnosis and information about the origin of the pain and the benign course of the condition will calm the majority of the patients and remove their fear of a possible fatal heart disease. PMID- 1736463 TI - [Cardiovascular diseases in Denmark in the year 2000. Occurrence, treatment and technology, developmental trends]. PMID- 1736464 TI - [Asthma as an immediate cause of death]. PMID- 1736465 TI - [Traffic chemistry--seen in the rear-view mirror]. PMID- 1736466 TI - [Menochaos]. PMID- 1736467 TI - [A direct military attack on the hospital in Osijek]. PMID- 1736468 TI - The epidemiology and prevention of sexually transmitted diseases. AB - Each year, approximately 12 million cases of STDs occur in the United States, including an estimated 1.4 million cases of gonorrhea, 130,000 cases of syphilis, 4 million cases of chlamydia, 500,000 to 1 million cases of human papillomavirus, 200,000 to 500,000 cases of genital herpes, and 45,000 cases of AIDS. These numbers should be viewed cautiously, because many STDs are not reported, many are not easily diagnosed, and many are asymptomatic or inapparent. The control of STDs can be achieved only through the continuing efforts of physicians to recognize and treat STDs and to counsel patients routinely in prevention. PMID- 1736469 TI - Fungal infections of the external genitalia. AB - In the era of the debilitated or immuno-compromised patient, fungal infections may become more prevalent. Unusual lesions of the external genitalia may be a manifestation of systemic infection. The urologist should be aware of this possibility when confronted with an unusual ulcer, inflammation, induration, or "abscess" of the external genitalia. PMID- 1736470 TI - Pigmentary disorders and inflammatory lesions of the external genitalia. AB - Many cutaneous processes can involve the external genitalia as a part of the general involvement of the skin. Other processes may affect only the genitalia, such as several pigmentary disorders and inflammations. As a result, these conditions may be mistaken for sexually transmitted diseases. It is important to include these conditions in the differential diagnosis. PMID- 1736471 TI - Benign lesions of the external genitalia. AB - Benign external genital lesions, being uncommon, can cause a significant diagnostic dilemma for the physician and anxiety for the patient. These lesions can be grouped into three categories: vascular lesions, nevi, and benign new growths. PMID- 1736472 TI - Acquired immunodeficiency syndrome. A venereal disease. AB - AIDS is clearly the most lethal of all the STDs. The universal adherence to "safe" sexual practices is required in order to try to limit this epidemic. Unfortunately, the other forms of transmission of HIV, intravenous injection and via the fetal-placental circulation, have ensured that simply altering the sexual practices of society would not be sufficient to end this epidemic quickly. PMID- 1736473 TI - Premalignant lesions and nonsquamous malignancy of the penis and carcinoma of the scrotum. AB - Premalignant lesions of the penis include cutaneous horn, balanitis xerotica obliterans, and leukoplakia. The true incidence of progression of each of these to squamous-cell carcinoma is unknown. Bowenoid papulosis, erythroplasia of Queyrat, and Bowen's disease are histologically identical to in situ carcinoma. Although the first is consistently benign, the latter two regularly evolve into invasive cancer. Malignant scrotal lesions include squamous-cell carcinoma, liposarcoma, leiomyosarcoma, basal-cell carcinoma, extramammary Paget's disease, erythroplasia of Queyrat, malignant melanoma, and metastases. Hemangioma can be confused with carcinoma. PMID- 1736474 TI - Balanitis and balanoposthitis. AB - Balanitis is an inflammation of the glans penis. There are several etiologic agents, including bacterial and yeast infections, parasitic infestations, and trauma or irritants. Plasma-cell balanitis and balanitis xerotica obliterans are two distinct clinical entities. The authors review the clinical and pathologic features and the treatment options for these conditions. PMID- 1736475 TI - Gangrene and Fournier's gangrene. AB - Fournier's gangrene is an aggressive disease affecting the perineum. Clearly, it can no longer by considered idiopathic in its origin, as most infection can be localized to a cutaneous, urethral, or rectal source. It presents in a broad age range and can have an indolent onset, thus requiring a high index of suspicion. It may be fulminant and progressive in the case of immunocompromise and underlying debilitating illnesses. Despite aggressive antibiotic therapy and debridement, it is associated with a high mortality rate. This rate has been higher in older patients, those with a rectal focus, and diabetics. Hyperbaric oxygen therapy has shown some promise in shortening hospital stays, increasing wound healing, and decreasing the gangrenous spread when used in conjunction with surgical debridement and antibiotics. New reconstructive efforts, such as medial thigh myocutaneous flaps, have improved the cosmetic aftermath of the extensive debridement. Fournier's gangrene remains a true urologic emergency, which mandates aggressive initial care by means of early recognition, early hemodynamic stabilization, and the institution of parenteral broad-spectrum antibiotics. This is followed by multiple debridements and in some cases urinary or rectal diversion. The concomitant use of hyperbaric oxygen therapy in selected cases followed by meticulous reconstructive surgery and salvage has further reduced the mortality rate and improved the cosmetic outcome. PMID- 1736476 TI - Management of voiding dysfunction with an implantable neuroprosthesis. AB - We have been very encouraged by these preliminary results concerning the efficacy and safety of functional electrical neuromodulation in the management of chronic voiding complaints. There are a large number of patients within the standard practice of urology who are potential candidates for this form of management. The techniques of peripheral nerve evaluation and implantation are relatively simple to master and free of significant risks or complications. If the long-term results of the multicenter clinical trial parallel our preliminary results, this is a technique which should be embraced by urologists as a significant therapeutic advance in our field. PMID- 1736477 TI - Update on bacterial sexually transmitted disease. AB - Sexually transmitted diseases (STDs) are the most frequently reported bacterial infections. In 1990, slightly more than 700,000 cases of gonococcal disease were reported to the Centers for Disease Control, and the estimated incidence of chlamydial infections is 3 million to 4 million annually. Bacterial genital ulcer diseases such as syphilis and chancroid are increasing in epidemic proportions. The author reviews bacterial STDs in two categories: exudative mucosal infections and genital ulcer diseases. PMID- 1736478 TI - Sexually transmitted diseases and their relation to male infertility. AB - Controversy surrounds the role of sexually transmitted diseases in male infertility. Because our understanding of male infertility is limited, and because diagnostic tests such as semen analysis including culture and leukocyte count are variable, definitive conclusions on STDs and their effect on infertility cannot be substantiated. Prospective investigations of infertile couples using appropriate control groups, sophisticated semen collection protocols, proper microbiologic techniques, and standardization of seminal fluid analysis are required to understand the role of STDs in male infertility. Regardless of the ongoing research to delineate the role of STDs in male infertility, advocating primary prevention by increasing public awareness of the negative effects of STDs and the use of contraceptive methods to prevent the spread of STDs is mandatory for the health care professional. PMID- 1736479 TI - Sexually transmitted protozoal infections. Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia. AB - Collectively, protozoa account for the largest number of STDs worldwide. Although these organisms can be eradicated effectively in the individual patient, their high asymptomatic carriage rate appears to have a significant influence on their continued transmission. The best hope for eradication of these organisms lies in a high index of suspicion in high-risk populations and the careful evaluation and treatment of sexual partners of infected persons. PMID- 1736480 TI - Determination of the calcium binding capacity to discriminate between urines of calcium stone formers and healthy persons. AB - Calcium binding by undiluted fasting urine has been tested as a means of demonstrating the capacity of urine from control subjects and calcium stone patients to hold spontaneous precipitation of stone forming compounds. Preliminary data are promising with respect to the possibility that controls and patients can be separated. PMID- 1736481 TI - The dual effect of urinary macromolecules on the crystallization of calcium oxalate endogenous in urine. AB - The nucleation-promoting and growth-inhibiting activities of urinary macromolecules on the crystallization of calcium oxalate endogenous in urine of stoneformers and normal controls were studied by freezing the ultrafiltrate and retenate fractions of concentrated whole urine (pH 5.3, 1,250 mosmol/kg). Among the normal controls, macromolecules nominally of 10-20 kDa showed nucleation promoting and growth-inhibiting activities; the 5-10 kDa population was incapable of such effects but did cooperate with molecules greater than 10 kDa in enhancing the effect. In the case of stone-formers, molecules in the nominal ranges of 5-10 kDa and 10-20 kDa when considered separately were not active in the aspects studied but collectively could cooperate to produce pronounced effects. Application of the test to urine ultrafiltrate reconstituted with polyanionic macromolecules recovered from urine indicated that molecules from stoneformers were more powerful than those from normal controls in bringing about promotion of nucleation and inhibition of growth of crystals from urinary calcium oxalate. PMID- 1736482 TI - Rationale for local toxicity of calcium chelators. AB - Calcium chelating agents, such as ethylenediaminetetraacetate are toxic to urothelium. Their capacity to form complexes with calcium ions, which is the basis for their chemolytical effectiveness, also determines their toxicity. A decrease of chemolytical effectiveness by prior saturation of the chelator with Ca2+ or by lowering the pH to levels unfavourable for calcium binding significantly diminishes tissue injury. Exchange of Mg2+ ions does not, however, diminish tissue damage. The clinical use of calcium ligands is therefore unsafe. PMID- 1736483 TI - Analysis of calcium, iron, copper and zinc contents of nucleus and crust parts of urinary calculi. AB - In this study we compared the concentrations of calcium, iron, copper and zinc in the nucleus and the crust parts of various kinds of urinary calculi. We found that the mean concentrations of iron, zinc and copper in the nucleus parts of the stones were statistically higher than those in the crust parts. We attempted to explain this finding by two different approaches. Inter- and intra-correlations were also sought between the elements in the nucleus and crust parts. These correlations suggested a complex relationship between the elements of the urinary calculi. PMID- 1736484 TI - Crystalluria in marathon runners. IV. Black subjects. AB - Crystal sizes (scanning electron microscopy) and distributions (Coulter Counter) as well as 24-h urinary sodium (Na) and calcium (Ca) excretions (flame atomic absorption) were determined in a group of black South African runners immediately after a marathon and again 3 weeks later. White runners and black and white control subjects were included in the study. Particle volume-size histograms for black controls and black runners were identical. There was no significant difference in the Na excretion of all the groups. However, while urinary Ca excretion was significantly raised in white runners relative to white controls, Ca excretion in black runners was unchanged relative to their controls. It is postulated that the lower rates of urinary Ca excretion may result from lower rates of Ca resorption from bone in response to the cyclical loading of running in black marathon runners. The results of this study suggest that black marathon runners are not prone to the same increased risk of renal stone formation as are white runners. PMID- 1736485 TI - The influence of pH and urine composition on urease enzymatic activity in human urine. AB - It is reasonable to assume that the rate of pH increase in urine induced by urease-producing microorganisms is one of the factors which determine whether crystallisation with subsequent stone formation will occur or not. To evaluate how the time needed to increase urine pH varies between different urine samples and how it depends on urine composition, a standardised amount of urease was added to different human urine samples. The incubations were performed in a pH stat. This allowed simultaneous study of how urease enzymatic activity depends on urine pH and how it varies between different urines. The enzymatic activity was found to be negatively correlated to urine pH and to vary between different urines. The rate of the pH increase varied markedly between different urines. Small pH increases depended on the native urine pH and urease enzymatic activity. Higher pH increases up to the levels of phosphate crystallisation depended more on urine phosphate, the major urine buffer. The results presented show that urine composition influences the urease-induced pH increase. This might have clinical implications. PMID- 1736486 TI - The influence of pelvic nerve transection on the neuromuscular system of the canine urinary bladder. AB - We previously reported that bladder overdistension led to denervation and subsequent supersensitivity of the detrusor muscle to acetylcholine. Therefore, to exclude the influence of bladder overdistension, we produced a low-pressure bladder in female mongrel dogs using an indwelling urethral catheter, and performed pelvic neurectomy (decentralization). We examined the effects of decentralization on the neuromuscular system of the bladder. The contraction response levels of bladder strips in dogs 1 and 2 weeks after neurectomy was low, and significantly different from that of bladder strips in the control group. The dose-response curves of dogs 4 and 8 weeks after neurectomy showed a shift to the left when compared to those of the control group, indicating a significant increase in sensitivity of the bladder strips. Many cholinergic terminal and varicosity profiles had a normal ultrastructure in all of the groups subjected to neurectomy, while some had degenerating profiles representing clear axoplasm without any recognizable organelles. Microphotographs of bladder obtained from dogs with spontaneous catheter loss showed degenerating axons, which were observed more frequently than in bladders kept empty with indwelling urethral catheters. Micturition in the dogs with spontaneous catheter loss was achieved by overflow incontinence without catheterization. These findings suggest that post synaptic nerve degeneration may be augmented by impairment of micturition, followed by decentralization. Our observations also suggest that post-synaptic nerve degeneration (denervation) plays an important role in the increased sensitivity of the detrusor muscle to acetylcholine in the parasympathetically decentralized urinary bladder, whether denervation is due to trans-synaptic degeneration or impairment of micturition. PMID- 1736487 TI - Effect of acute distension on cholinergic innervation of the rat urinary bladder. AB - The effect of short-term urinary bladder distension on its cholinergic innervation was studied in Sprague-Dawley rats. Distension was induced for 3 h by forced diuresis and balloon outlet obstruction, and whole thick biopsy specimens were taken from the dome and lateral side of the anterior body 2, 7 and 21 days afterwards. The acetylcholinesterase (AChE) method was used to demonstrate the cholinergic nerves in the distended bladder wall. Cholinergic hypoinnervation was observed 7 days after the distension, persisting up to 21 days, although AChE reactive nerves were then observed to be more numerous. The distribution of hypoinnervation was uneven, being more marked in the lateral side of the anterior body than in the dome. The distribution of AChE-reactive nerves varied even in the same biopsies, with areas of total hypoinnervation occurring next to areas of slightly diminished innervation. This was especially true 21 days after distension. The findings indicate transient damage to the cholinergic innervation, which may in turn explain the prolonged voiding difficulties often seen after catheterization of an overdistended bladder in a patient with urinary retention. The short-lasting effect of bladder dilatation therapy used to treat detrusor instability or interstitial cystitis may be due to the fairly rapid regeneration of cholinergic innervation. PMID- 1736488 TI - Urinary endothelin (ET1) in complete ureteric obstruction in the miniature pig. AB - Segmental renal scarring occurs in experimental obstructive uropathy in the multipapillary porcine kidney, and segmental abnormalities in renal perfusion are likely to be responsible. This preliminary study examines the urinary excretion of the potent locally active vasoconstrictor endothelin 1 (ET 1) in a pig model of renal obstruction and subsequent relief. Significant urinary excretion of ET 1 from the postobstructive kidney was found to occur after longstanding obstruction. Preglomerular arteriolar stenosis may be the cause of the renal ischaemia in obstruction that is at first reversible but later becomes irreversible if the stimulus persists. ET 1 may be implicated in the pathogenesis of this injury. PMID- 1736489 TI - Estimation of irrigant absorption during transurethral resection of the prostate. Assessment of fluorescein as a marker. AB - Absorption of irrigating solution may complicate transurethral resection of the prostate (TURP), and a system which warns of fluid overload reliably would be of benefit in the prevention of these complications. Fluorescein can easily be detected at very low concentrations in blood and can be added to the irrigating solution in amounts invisible to the naked eye, providing a possible means of easily monitoring the absorption of irrigant solution during TURP. To test this hypothesis, the plasma concentration of fluorescein was determined at intervals after intraperitoneal injection in rats. Although the published data on fluorescein suggest that it meets the criteria for a suitable marker substance to be introduced into the irrigant solution, the results show that plasma fluorescein is constant and not dose related. The addition of fluorescein to the irrigant solution would not provide a quantitative means of determining the volume of irrigant absorbed. The use of other substances may provide the answer to this major clinical problem. We have defined a set of criteria which such a substance should fulfil. PMID- 1736490 TI - Investigations on macromolecular precipitation inhibitors of calcium oxalate. AB - Certain important aspects of the urine oxalate tolerance test (OTT) have been revised. The stirring system has been changed and the test has been adapted to the kinetics of calcium oxalate precipitation. True equilibrium conditions are now ensured during the measurements. Furthermore, the endogenous oxalate concentration is determined and taken into consideration. As a result of these changes, the significance of the test results has greatly improved. The effects of the addition of small amounts of zinc on the precipitation of calcium oxalate have been used in a new variation of the OTT. This new test makes it possible to discriminate much faster and more simply between recurrent stone-formers and other subjects. Tamm-Horsfall protein (THP) has been tested for its effect on the precipitation of calcium oxalate by means of OTT. THP inhibits the precipitation of calcium oxalate, but THP of stone-formers has a diminished inhibitory activity. The inhibitory activity of this protein strongly depends on the method by which it is isolated. PMID- 1736491 TI - Environmental factors in the pathophysiology of recurrent idiopathic calcium urolithiasis (RCU), with emphasis on nutrition. AB - A number of environmental factors are under discussion as possibly implicated in the etiology of RCU. On the basis of data in the literature and our own results, we attempted a critical weighting up of the possible contributions of climate, pollution, stress, nutrition in general and especially oxalate and minerals in the nutrition. It was concluded that there is a need for more in-depth research into the response of the body to challenges from the environment, in particular nutrition. PMID- 1736492 TI - Tamm-Horsfall glycoprotein--inhibitor or promoter of calcium oxalate monohydrate crystallization processes? AB - The processes of calcium oxalate monohydrate (COM) crystal nucleation, growth and aggregation (agglomeration) generally have been studied using a wide variety of assay systems/conditions. This paper reviews the apparently conflicting data on the effects of Tamm-Horsfall glycoprotein (THP) on COM crystallization processes in vitro, with the main emphasis on crystal aggregation. According to its well known physico-chemical properties, THP has a dual role in modifying crystal aggregation: at high pH and low ionic strength (IS). THP is a powerful crystal aggregation inhibitor. Upon lowering pH and raising IS, THP viscosity increases, leading to reduced crystal aggregation inhibition. In the presence of additional calcium ions, some THPs even become strong promoters of crystal aggregation. This phenomenon seems to be more pronounced in THPs isolated from recurrent calcium stone formers whose proteins exhibit an abnormally high tendency of polymerization. Recent studies suggest an inherited molecular abnormality of THP among some severe recurrent calcium stone formers. PMID- 1736493 TI - Urolithiasis, inhibitors and promoters. AB - The aim of this work is to evaluate the role and importance of inhibitors and promoters in urolithiasis. Carrying in mind theoretical considerations, we conclude that in urolithogenic processes, inhibitors and promoters could only play a decisive role in the "idiopathic" oxalocalcic urolithiasis. We classify the "idiopathic" oxalocalcic stone-formers into three main groups, considering inhibitory and promoting factors. It is shown that such classification is in good agreement with the clinical results observed in a group of 88 "idiopathic" oxalocalcic stone-formers. PMID- 1736494 TI - Role of citric acid in primary hyperparathyroidism with renal lithiasis. AB - Nephrolithiasis is presented in 18-40% of patients with primary hyperparathyroidism. Our work suggests that citrate, an inhibitor of calcium salts, could be involved in the presence of renal lithiasis because hyperparathyroid stone formers show less citrate elimination than nonstone formers. PMID- 1736495 TI - Advances in medical treatment of renal stones. PMID- 1736496 TI - Prevention of recurrent stone formation: long time results under treatment based on an extended metabolic investigation. PMID- 1736497 TI - Correlation between 1.25 dihydroxyvitamin D serum levels and fractional rate of intestinal calcium absorption in hypercalciuric nephrolithiasis. Role of phosphate. AB - Different mechanisms could explain the elevated calcium elimination, the main cause of calcium oxalate renal stones. Our results suggest that phosphate levels are decreased in patients with absorptive hypercalciuric nephrolithiasis and elevated serum dihydroxyvitamin D. This could be the reason why in this group of patients oral phosphate treatment prevented hypercalciuria and renal lithiasis. PMID- 1736498 TI - Recurrent nephrolithiasis in renal tubular acidosis. Metabolic profiles, therapy and course. AB - 13 patients with recurrent urolithiasis and distal renal tubular acidosis (RTA I) were investigated for lithogenic metabolic disorders. Treatment was given and the patients observed for periods of up to 10 years. PMID- 1736499 TI - Nocturnal penile tumescence in cigarette smokers with erectile dysfunction. AB - We examined the relationship between cigarette smoking and erectile physiology in 314 men with erectile dysfunction. All of the men studied were currently cigarette smokers. Evaluations included interviews, physical examinations, and polysomnographic assessment of sleep-related erections. Penile rigidity during nocturnal erection inversely correlated with the number of cigarettes smoked per day. Smoking was also associated with indices of impairment on autonomic function tests and some measures of penile blood pressure. The group of men who smoked the most (more than 40 cigarettes per day) had the fewest minutes of nocturnal tumescence and detumesced fastest. These data are discussed with respect to the results of studies performed in dogs that demonstrated smoking-related reduction in arterial flow and venous restriction. Our findings suggest that smoking may further compromise penile physiology in men experiencing difficulty in maintaining erections long enough for satisfactory intercourse. PMID- 1736500 TI - Diethylstilbestrol in treatment of postorchiectomy vasomotor symptoms and its relationship with serum follicle-stimulating hormone, luteinizing hormone, and testosterone. AB - Vasomotor symptoms such as hot flushes and profuse sweating have been described after bilateral orchiectomy. We evaluated 26 patients who had undergone bilateral orchiectomy for prostatic carcinoma to determine the incidence of vasomotor symptoms and the efficacy of low-dose diethylstilbestrol (DES) in the treatment of those symptoms. Measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were performed to look for endocrine patterns which may be related to the presence of vasomotor symptoms. Fourteen patients (54%) reported the presence of vasomotor symptoms beginning one to four weeks after surgery. These patients were treated with DES or placebo in a double blind crossover trial. The frequency and severity of hot flushes were significantly reduced during the time DES was given. This was accomplished with a low dose of 1 mg daily of DES which avoids the cardiovascular complications of higher doses. We found no correlation between the presence, severity, or frequency of hot flushes and serum gonadotropin or testosterone concentrations. PMID- 1736501 TI - Multivariate case-control study of survival following transurethral resection of prostate. AB - Although prevalence of perioperative mortality following transurethral resection of the prostate (TURP) has steadily declined as reported in several review studies, it has been suggested that with extended follow-up after TURP, mortality exceeds that of an age-matched population. The sample selected for this study was drawn from a data base of 2,005 men who entered a urologic health-screening program. The sample included a group of 25 patients who underwent TURP and a group of 50 age-matched control patients with symptoms of prostatism. Patients were followed for six years, a total of 450 observed person-years. Multivariate analyses based on a general linear model approach for the dependent variable of survival were used to assess gains in predictive efficiency due to combinations of TURP versus control, time, and patient variables. F-ratio hypothesis tests of coefficients of multiple determination for the models indicated that TURP did account for a significant amount of the variability of survival but only after five years of follow-up. However, a far larger proportion of the variance in survival was explained by other patient variables of age, preoperative risk, comorbidity factors, and postoperative urinary disease after all effects due to TURP, follow-up years, and operation cohort years were held constant in the survival prediction equation. PMID- 1736502 TI - Preservation of urosexual functions after radical cystectomy. AB - Nerve-sparing radical cystectomy with ileocecal bladder substitute is highly recommended for male patients with schistosomal bladder carcinoma and for selected male patients with transitional cell carcinoma. Twenty-three patients underwent this procedure with preservation of the distal one third of prostatic capsule and inframontanal urethra, reinforcement of the ileocecal valve, and tightening of the two levator ani muscles over the cecourethral anastomosis. Urodynamic study revealed that the closed ileocecal segment is a highly compliant reservoir, and coupled with a reinforced ileocecal valve and distal urethral mechanism resulted in a low incidence of ureteral reflux (15%) and a high degree of urinary continence (100% by day and 40% by night). The procedure does not appear to undermine the principles of oncologic surgery, offers the psychologic and functional benefits of urethral micturition for all patients, and preserves erectile potency in half of them. PMID- 1736503 TI - Analysis of imaging modalities, staging systems, and prognostic indicators for renal cell carcinoma. AB - A retrospective analysis of 314 patients with renal cell carcinoma was done focusing mainly on imaging modalities and prognostic significance of tumor stage using both the Robson and TNM systems. Computerized tomography (CT) scan proved to be the most effective modality for staging. Overall staging accuracy was 62 and 68 percent for TNM and Robson staging, respectively, and understaging was more frequent than overstaging. The actuarial five-year survival using the Robson system was 73 percent for Stage A, 68 percent Stage B, 51 percent Stage C, and 20 percent Stage D. The main limitation of the Robson system is the heterogeneity of the Stage C group which includes patients with renal vein and those with nodal involvement with a significant difference in survival. The survival by the TNM system showed no difference in those with T1, T2, T3a and T3b disease but a significant difference in those with T3c or T4a. One hundred sixteen patients (37%) presented with metastatic disease with a median survival of seventeen months (range 2-204) for those with solitary metastasis and six months (range 1 132) for those with multiple metastases (the difference was not statistically significant). Except for anecdotal cases, nephrectomy with or without treatment of the metastases did not seem to affect survival significantly. The presence of spindle cell, alone or in association with clear or granular cell, affected the prognosis adversely. Thirty-one patients had their tumors identified incidentally. Their stage at diagnosis was earlier than the symptomatic group (Stage T1-T2: 77% vs 34%), and there was a significant difference in the disease free survival at fifty-four months between the two groups (79% vs 57%, respectively). PMID- 1736504 TI - Nuclear morphometry in prognosis of renal adenocarcinoma. AB - Nuclear morphometry was carried out on 95 parenchymatous adenocarcinomas of the kidney treated by radical nephrectomy and hilar lymphadenectomy and followed up for at least five years. The study assessed nuclear area, nuclear perimeter, major diameter, nucleolar area, nuclear shape factor, and nuclear size. There was a significant statistical correlation between survival and the morphometric parameters and between the parameters themselves except for nuclear shape factor. The multiple regression proved that nuclear area is the factor which shows the greatest statistical significance for prognosis. Taking a mean nuclear area of 35 microns 2 allowed two prognostic groups to be established regardless of stage, with those below the threshold having a good prognosis and those above it having a poor prognosis: 96.7 percent of patients with a good prognosis survived after five years (60 months) compared with 17.2 percent of those with a poor prognosis. PMID- 1736505 TI - Primary endourologic re-establishment of urethral continuity after disruption of prostatomembranous urethra. AB - A new technique for the early management of traumatic disruption of the prostatomembranous urethra has been used in 4 consecutive young patients. Urethral realignment by stenting the injured urethra with a catheter was achieved by combined urethroscopy and suprapubic instrumentation one to three days after the injury. We describe herein our experience with this technique and we suggest that it could be a valuable alternative in posterior urethral repair. PMID- 1736506 TI - Twelve-month comparison of two treatments for erectile dysfunction: self injection versus external vacuum devices. AB - This study directly compared two nonsurgical treatments for erectile dysfunction, self-injection of papaverine/phentolamine and external vacuum devices, in terms of usage rates, effectiveness, side effects, dropout rates, and impact on patient sexual and psychologic functioning. Both alternatives were regularly, successfully, and safely used by patients, though dropout rates were higher for self-injection. Both produced erections of improved quality, and effected sustained improvements in frequency of intercourse, orgasm, and sexual satisfaction. Spontaneous erections also improved with both treatments. General psychiatric symptomatology was decreased, and anxiety was improved. There were no differences between the two treatments in sexual or psychologic impact. Relative contraindications and esthetic considerations are presented. PMID- 1736507 TI - Endoscopic management of complications of continent urinary diversion. AB - The Kock pouch continent ileal reservoir has become a therapeutic option for those patients requiring urinary diversion. Complications of this procedure do occur but fortunately many of these may be managed endoscopically without need for open surgical exploration. This report describes experience with 55 patients treated by endoscopic surgery for complications of Kock pouch urinary diversion. This includes 45 patients with stones, 3 with stenotic afferent nipple valves, 3 with suspicion of ureteral or renal pelvic tumor, and 4 with retained upper urinary tract stents. These patients may be treated with intravenous sedation only on an outpatient basis. The procedure was successful in all but 2 patients. One complication occurred when extravasation was noted from the afferent limb. The patient was treated by internal diversion, and follow-up urogram done in forty-eight hours was normal. This experience confirms that endoscopic surgery is an attractive option for treatment of many of the complications resulting from creation of a Kock pouch ileal reservoir. PMID- 1736508 TI - Clinical value of scrotopenogram for evaluating varicocele and erectile dysfunction. AB - While there is as yet no established theory regarding a possible relationship between varicocele and erectile failure, it is not uncommon to encounter those cases in which two conditions coexist clinically. We describe a new technique to identify these two conditions by a single injection of radioisotope. In scrotopenogram, varicocele is diagnosed by comparing the radioactivity in each hemiscrotum during the five minutes after injection of radioisotope. Then, after the patient is exposed to audiovisual sexual stimulation, the dynamic penile flow is measured for the next thirty minutes. We evaluated 185 impotent patients and 9 patients with varicocele. In the 185 erectile failure patients, varicoceles were also present in 33 (17.8%). In the 9 patients who presented themselves chiefly with varicoceles, 3 (33.3%) also had erectile failure. Thus, in 194 patients 36 (18.5%) cases of combined conditions were identified by the scrotopenogram technique. We believe this new technique could be an alternative method for noninvasively examining impotent patients with varicoceles. PMID- 1736509 TI - Infected multicystic displastic kidney. PMID- 1736510 TI - Transitional cell carcinoma of bladder in thirteen-year-old boy. AB - We report a rare case of primary epithelial bladder tumor in a thirteen-year-old boy. Histologically, the tumor was that of a solitary and papillary transitional cell carcinoma, grade 1. This tumor was detectable at cystoscopic examination, and cytologic procedures were without benefit for a diagnosis. PMID- 1736511 TI - Endoscopic correction of primary vesicoureteric reflux in children. AB - Sixty-nine children with 113 refluxing ureters were followed prospectively after treatment with endoscopic injection of subureteric polytetrafluoroethylene (sting). The 50 female and 19 male patients had a total of 105 procedures. Thirty eight patients have had their vesicoureteric reflux (VUR) resolved, and 16 now have asymptomatic grade I or II reflux, giving a combined patient VUR improvement rate of 80 percent. PMID- 1736512 TI - Temporal separation of cough-induced urethral and bladder pressure spikes in women with urinary incontinence. AB - The time separation of cough-induced urethral and bladder pressure spikes were studied in 32 female patients: 16 with urinary incontinence due to sphincter incompetence, 9 with urinary incontinence and a competent urethral closure mechanism, and 7 after incontinence surgery. There were no significant differences in time separation between the three groups at different positions in the urethra. Age and menopausal status did not affect time separation of pressure spikes. It is concluded that time separation of pressure spikes during cough cannot be used as a discriminator of the etiology of urinary incontinence. Surgery does not restore the latency seen in normal continent women and may restore continence by a mechanism different from that of normal continent women. PMID- 1736513 TI - Interferon-induced reversible acute renal failure with nephrotic syndrome. AB - Although there has been considerable experience with interferons in clinical trials during the past decade, acute renal failure as a side effect of interferon treatments has rarely been reported. We report a case in which acute renal failure with nephrotic syndrome was associated with therapy with two types of interferons. We note incomplete return of renal function upon withdrawal of therapy. PMID- 1736514 TI - External spermatic sheath injection for vasal nerve block. PMID- 1736515 TI - Anterior rectal wall hematoma: complication of transrectal ultrasound-guided biopsy of prostate. AB - Transrectal biopsy of the prostate, because of its directness and simplicity, is utilized by many practicing urologists to obtain prostatic tissue for histologic evaluation. Complications arising from this procedure are primarily of an infectious origin and less commonly of a vascular etiology. We report on the first known patient in whom a large hematoma of the anterior rectal wall with nearly total occlusion of the rectal lumen developed following a transrectal ultrasound-guided biopsy of the prostate. Guidelines to reduce the likelihood of vascular complications following biopsy of the prostate gland for patients consuming medications that may alter normal platelet function or interfere with the various clotting factors are described. PMID- 1736516 TI - Primary radiologic realignment of membranous urethral disruptions. AB - A forty-two-year-old man with a traumatic, membranous urethral disruption underwent initial suprapubic catheter urinary diversion followed by a primary realignment twenty-one days after injury. Realignment was accomplished radiologically using an anterograde guide wire engaged by a retrograde stone basket and subsequent Foley catheter placement over the wire. The patient has remained totally continent, having partial erections, two years after injury, with no further intervention. PMID- 1736517 TI - Excretory urography during extracorporeal shock-wave lithotripsy: a localization alternative. AB - An alternative localization technique or extracorporeal shock wave lithotripsy using devices that use fluoroscopic targeting is presented. Excretory urography during lithotripsy can provide valuable targeting information and the results of treatment in a manner that may prove useful in the treatment of urinary calculi. PMID- 1736518 TI - Hematuria following bladder augmentation. PMID- 1736519 TI - Acquired cystic disease of kidney associated with renal cell carcinoma in chronic dialysis patients. AB - We describe 2 cases of acquired cystic disease of the kidney (ACDK) associated with renal cell carcinoma in patients treated with long-term hemodialysis. Both patients have had dialysis for five and eight years, respectively. Renal cell carcinomas of these patients are small, averaging 2 cm in diameter. They are clear cell type. Atypical epithelial hyperplasia arising from cystic areas can be seen intermingling with carcinoma. This confirms that atypical epithelial hyperplasia is a precursor of renal cell carcinoma. Although the incidence of renal cell carcinoma arising in ACDK is on the rise, the issue of how to manage patients with ACDK remained unsettled and required further study. PMID- 1736520 TI - Enuresis and voiding cystourethrogram. PMID- 1736521 TI - Kinetics of tomato golden mosaic virus DNA replication and coat protein promoter activity in Nicotiana tabacum protoplasts. AB - We have analyzed the replication kinetics of the DNA A and DNA B genome components of the geminivirus tomato golden mosaic virus (TGMV) in protoplasts derived from Nicotiana tabacum suspension culture. In addition, the kinetics of TGMV coat protein promoter activity, as measured by expression of a beta glucuronidase (GUS) reporter, have been examined. In our protoplast system, double-stranded DNA forms of both viral genome components appeared by 18 hr post transfection, while single-stranded DNA accumulated to detectable levels after 18 24 hr. Expression of GUS from the TGMV coat protein promoter did not require viral DNA replication, nor was it dependent on expression of AL1, the only viral gene necessary for DNA replication. However, maximal expression was achieved following AL1-mediated replication of DNA A. GUS activity from replicating templates exceeded that from nonreplicating templates by 60- to 90-fold. Expression of the GUS reporter gene from nonreplicating viral DNA templates was similar to GUS expression from the 35S promoter of cauliflower mosaic virus in N. tabacum protoplasts. PMID- 1736522 TI - Parvovirus H-1 P38 promoter requires the trans-activation region (tar), an SP1 site, and a TATA box for full activity. AB - In the parvovirus H-1 P38 promoter, there are sequences identified as a TATA box, an SP1 site, and a trans-activation responsive element (tar). It was previously shown that the parvovirus H-1 nonstructural protein NS1 positively regulates the expression of the P38 promoter for the viral capsid protein gene via the tar. To characterize the tar element further, a series of single-point mutations of the tar was constructed and the mutants were compared to wild-type for the trans activation of the P38 promoter using a cat reporter gene. Most of the tar mutations had a negative effect on the P38 promoter and some of them reduced activity as much as 70%. However, when several mutants with multiple-point mutations in the tar were tested, no significant additive effect was observed. We examined the function of the SP1 site in the trans-activation of the P38 promoter by replacing the wild-type SP1 sequence with synthetic DNA fragments, OSP1 or 2SP1, containing no SP1 or two SP1 sites respectively, in a P38 construct with a cat reporter gene. The results indicate that P38 expression varies in proportion to the number of SP1 sites, suggesting a role for the SP1 site during trans activation by NS1. The role of the TATA box on the P38 promoter was also examined by mutagenizing TATA to CACG. The activity of this promoter was reduced to 43%. When a construct mutated at both the SP1 and TATA box sites was tested for its activity, about 22% of the wild-type activity remained, implying that this remaining activity was contributed largely by the tar element. A model is proposed for how the tar element activates the wild-type and SP1-TATA minus promoters in the presence of NS1. PMID- 1736523 TI - Expression of ORF-69 of turnip yellow mosaic virus is necessary for viral spread in plants. AB - Turnip yellow mosaic virus (TYMV) RNA has two extensively overlapping open reading frames (ORFs) encoding noncapsid proteins. The longest of these, ORF-206, is essential for RNA replication. We have investigated the expression and role of ORF-69 (encoding a protein with a MW of 69K) using specific antiserum and mutant genomic RNAs designed to interrupt ORF-69 expression. TYC69 antiserum immunoprecipitated a protein with an apparent MW of 75K (p69) from in vitro translations of TYMV RNA. Mutant RNAs with stop codons inserted at nucleotides 139, 178, and 178/224 in ORF-69 expressed ORF-69 at very low levels in vitro. These mutants replicated to wild-type levels in turnip or Chinese cabbage protoplasts, but were not recovered from any leaves of inoculated plants. These results suggest that ORF-69 products are dispensible for replication, but are required for viral spread. Revertant and pseudorevertant viruses with uninterrupted ORF-69 were recovered from plants showing delayed onset of symptoms after inoculation with two of the above mutants, indicating the importance of ORF 69 expression in establishing a systemic infection in plants. ORF-69 expression could be detected using Western blots in extracts from young, symptomatic leaves of infected plants. A single band with an apparent MW of 75-80K was detected in leaves infected with cDNA-derived viral RNAs, while a doublet was detected after infection with type strain viral RNA, suggesting the presence of two ORF-69 alleles or differential post-translational modification. PMID- 1736524 TI - Translational effects and sequence comparisons of the three serotypes of the reovirus S4 gene. AB - Reovirus S4 RNA codes for the dsRNA-binding polypeptide sigma 3, a major virion outer capsid component that also has translational effects in both infected and transfected mammalian cells. To compare the composition and properties of the three different serotypes of sigma 3, a DNA copy of the type 2 gene was cloned and sequenced. The total lengths (1196) and the sequences of leader (33 nucleotides) and trailer (66 nucleotides) regions are highly conserved among the three S4 serotypes. The type 1 and 3 S4 genes are highly related (77 mismatches). However, the type 2 gene contains many mismatches relative to the type 1 and 3 genes (260 and 270 positions, respectively). Most of the mismatches are third position changes, resulting in sigma 3 polypeptides that are 90% or more identical. Transient expression vectors, constructed by replacing the chloramphenicol acetyltransferase (CAT) gene in pRSVCAT with S4 DNA, were used to test the effects of polypeptide sigma 3 on CAT expression in cotransfected COS cells. Transfection with the correctly oriented DNAs resulted in synthesis of the corresponding sigma 3 polypeptides which enhanced CAT expression. The type 2 and type 3 S4 genes were considerably more stimulatory than type 1 when compared to CAT DNA alone. However, with all three serotypes the CAT activity was significantly higher in cells cotransfected with S4 DNA in the correct orientation as compared to the reverse arrangement. PMID- 1736525 TI - PreS1-specific binding proteins as potential receptors for hepatitis B virus in human hepatocytes. AB - Cellular receptors play an important role in viral pathogenesis. Until now, there has been no reliable information on the receptor(s) for hepatitis B virus (HBV). Therefore, we attempted to identify specific receptors in human hepatocytes using an immunological approach. Anti-idiotypic (Ab2) antibodies were raised in rabbits against our monoclonal antibody (MAb1) F35.25. MAb1 F35.25 (i) recognized the hepatocyte receptor binding site on HBV (located between amino acid residues 21 and 47 of the preS1 sequence) and (ii) blocked the attachment of preS1-positive HBV particles to human hepatocytes. The presence of Ab2 antibodies in rabbit sera was determined by the ability of antisera to inhibit Id (Ab1)/antigen (HBV) recognition. Affinity-purified Ab2 IgGs to F35.25 represented an internal image for the preS1 domain 12-53. Our present studies indicate that Ab2 IgGs to F35.25 (i) recognized the membrane-associated structure of the preS1-specific HBV receptor in a HepG2 cell binding assay, as visualized by immunoenzymatic staining; (ii) strongly bound to a major 35-kDa component and to three other related proteins of 50, 43, and 40 kDa in extracts of HepG2 cells; and (iii) reacted with several soluble and membrane-associated proteins in normal human liver cells. The binding was insensitive to reduction. All preS1 binding proteins were V8 protease sensitive and endoglycosidase H resistant. The 35-kDa species was trypsin resistant and generated a band of 32 kDa by endoglycosidase F treatment. Together, our results suggest that the identified preS1-specific binding proteins may be involved in the putative complex structure of the hepatocyte receptor for HBV. PMID- 1736526 TI - Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex. AB - Utilizing a recombinant vaccinia expression system, we investigated the biological properties and CD4 receptor interactions of the envelope glycoproteins of a noncytopathic human immunodeficiency virus type 2 strain, termed HIV-2/ST, and a highly cytopathic variant derived from it. The efficiency and host cell range of syncytium formation by the recombinant glycoproteins of both viruses were highly restricted compared to those of prototypic strains of HIV (HIV-2/ROD or HIV-1/IIIB). However, the glycoprotein of cytopathic but not wild-type ST generated numerous large syncytia in the human T-cell line Sup T1 from which it was derived. A single cell line (Molt 4 clone 8) was permissive to fusion by both wild-type and cytopathic ST envelopes, but only the glycoprotein of cytopathic ST could be inhibited with a soluble form of the viral receptor CD4 (sCD4). While these results indicated major differences in the envelope glycoprotein-CD4 receptor interactions of wild-type versus cytopathic ST, direct and competition binding assays utilizing soluble external glycoprotein (SU) and sCD4 surprisingly revealed equivalent low binding affinity for both viruses. From these experiments we conclude that relevant biological properties (e.g., CD4 binding, cytopathic potential, and sCD4 neutralization) of HIV viruses which differ in their pathogenic potential are reflected in the sCD4 interactions of the assembled native envelope complex (as on cell or virion surfaces) but not the soluble SU glycoprotein. PMID- 1736527 TI - Characterization of vaccinia virus glycoproteins by monoclonal antibody precipitation. AB - Monoclonal antibodies were used to characterize vaccinia virus glycoproteins known to be incorporated into the envelope of extracellular enveloped vaccinia (EEV) virus. The 89K hemagglutinin, 42K, and 23-28K glycoproteins were predominantly expressed as late vaccinia proteins. The 89K glycoprotein was sulfated and phosphorylated but not acylated. 89K precursor proteins of 32K, 41.5K, and 52K were detected. The former had a molecular weight expected from the deduced amino acid sequence of the hemagglutinin gene. A 76K glycoprotein that did not contain methionine and was not sulfated or phosphorylated was precipitated late in infection by the anti-hemagglutinin monoclonal antibody. The appearance of this protein was inhibited by rifampicin and it may thus result from 89K cleavage. A 220K complex contained some or all of the hemagglutinin gene products linked by disulfide bonds. The 42K glycoprotein was not sulfated or phosphorylated but was acylated. This glycoprotein was disulfide bonded with the EEV 37K nonglycosylated envelope protein. The 23-28K glycoprotein was not sulfated but was both phosphorylated and acylated. The 23-28K glycoprotein group of five proteins had a common protein backbone that was differentially glycosylated. Pulse-chase, glycosylation inhibition with tunicamycin, and glycosidase experiments established that the precursor to the 23-28K glycoproteins was a 21K protein. Members of this protein family formed dimers of approximately 55K through disulfide bonds. PMID- 1736528 TI - Unique nucleotide differences in the conserved 3' termini of brome mosaic virus RNAs are maintained through their optimization of genome replication. AB - To explore the functionality and conservation of specific base differences in the 3' 200 nucleotides of brome mosaic virus (BMV) RNA-1 (1t) and RNA-2 (2t) with respect to the 3' end of RNA-3 (3t), all possible permutations were used to exchange these regions among the genomic RNAs. When all RNAs bore the 1t promoter, total RNA accumulation was only 15% of wild type; when the 2t or 3t promoter was present on all three RNAs total RNA accumulation was reduced to 30 or 35% of wild type. Two major processes were found to be involved in these dramatic differences. The first reflects the distinct and competitive strengths of the (-)-strand promoters in these sequences, which were shown to have a 3t greater than 1t greater than 2t hierarchy. The second is the importance of the context of upstream sequences in which the 3' promoter is placed. Important contributions of the 3t promoter in preferential amplification of RNA-3 were apparent from changed RNA 1 + 2: 3 ratios and reduced progeny accumulation from transfections using the RNA-3/1t chimera. These interactions contribute to temporal modulation as well as overall optimization of viral RNA functions, leading to selection and maintenance of the specific base differences present in the otherwise highly conserved 3' 200 nucleotides of each genomic RNA component of BMV. PMID- 1736529 TI - Frequent and rapid emergence of mutated pre-C sequences in HBV from e-antigen positive carriers who seroconvert to anti-HBe during interferon treatment. AB - Hepatitis B virus (HBV) variants which cannot express e-antigen (HBeAg) are characteristic for many viremic anti-HBe positive chronic carriers who often have particularly severe and fluctuating hepatitis. Whether such variants are selected for and are less amenable to interferon treatment is under dispute. Therefore, by DNA amplification and direct sequencing we have investigated the emergence of HBV pre-C sequence variants in nine e-antigen positive chronic carriers, all of whom seroconverted to anti-HBe or lost HBeAg during interferon treatment, and in three of whom no viral DNA was detectable after interferon treatment. In most, but not all of the patients we found newly emerging pre-C sequences in a subpopulation of the viral genomes that included silent point mutations, amino acid changes, start and stop codon and frameshift mutations. The emergence of these mutations was paralleled by a drastic decrease of viremia during treatment. The observed mutations appeared most frequently during interferon treatment. Some of the mutations appeared or disappeared late after interferon treatment concomitant with anti-HBe antibody development. The appearance or lack of mutations in the pre-C region of a subpopulation of HBV of these patients was independent of successful virus elimination. These data indicate that interferon treatment is frequently associated with the simultaneous fall in titer of viral DNA by several orders of magnitude and the emergence of novel pre-C sequences, some of them preventing HBeAg expression. However, the presumably immune-mediated selection for pre-C mutant viruses and decrease in viremia under interferon treatment appears not to be prognostic for successful or unsuccessful virus elimination. PMID- 1736530 TI - Measles virus inhibits mitogen-induced T cell proliferation but does not directly perturb the T cell activation process inside the cell. AB - Measles virus (MV) inhibits lymphocyte function in patients, as well as in cells infected in vitro. The proliferation of phytohemagglutinin-stimulated T lymphocytes is suppressed by in vitro MV infection, as shown by the diminished incorporation of [3H]thymidine into DNA and the reduced frequency of cells in the S phase of the cell cycle, as compared with mock-infected cells. MV infection itself, however, does not completely block DNA synthesis in infected cells, because infected T cells expressing MV antigens on the cell surface, isolated by fluorescence-activated cell sorter, could still proliferate. Northern blot analysis indicated that the expression of genes induced during T cell activation, such as those encoding interleukin 2 (IL-2), c-myc, IL-2 receptor, IL-6, c-myb, and cdc-2, was not significantly suppressed in MV-infected cells, suggesting that MV does not interfere with the T cell activation process. When anti-MV serum or carbobenzoxy-D-Phe-L-Phe-Gly, a synthetic oligopeptide known to inhibit MV induced fusion, was added 24 hr after infection, the inhibition of T cell proliferation was reversed in a dose-dependent manner. From these results we propose a model for the inhibition of T cell proliferation by MV; MV glycoproteins expressed on the cell surface of infected cells interact with the MV receptor or other molecules on the cell membrane of adjacent T cells, which in turn affects the proliferation of those T cells. PMID- 1736531 TI - Recombinant vaccinia virus producing the prM and E proteins of yellow fever virus protects mice from lethal yellow fever encephalitis. AB - Four recombinant vaccinia viruses were constructed for expression of different portions of the 17D yellow fever virus (YFV-17D) open reading frame. A recombinant, vP869, expressing prM and E induced high titers of neutralizing and hemagglutination inhibiting antibodies in mice and was protective against intracranial challenge with the French neurotropic strain of YFV. Levels of protection were equivalent to those achieved by immunization with the YFV-17D vaccine virus. Recombinant vaccinia viruses expressing E and NS1, C prM, E, NS1, or only NS1 failed to protect mice against challenge with YFV despite eliciting antibodies to NS1. The vP869-infected HeLa cells produced a particulate extracellular hemagglutinin (HA) similar to that produced by YFV-infected cells, supporting previous studies with Japanese encephalitis virus (Mason et al., 1991), suggesting that the ability of recombinant vaccinia virus to produce extracellular HA particles is important for effective flavivirus immunity. PMID- 1736532 TI - Substantial portions of the 5' and intercistronic noncoding regions of cowpea chlorotic mottle virus RNA3 are dispensable for systemic infection but influence viral competitiveness and infection pathology. AB - Cowpea chlorotic mottle virus (CCMV) has a tripartite, positive strand RNA genome. Genomic RNA3 (2.2 kb) encodes the 3a nonstructural protein and the coat protein, which are dispensable for viral RNA synthesis in protoplasts, but required for systemic infection of whole plants. In protoplasts, portions of the 5' and intercistronic noncoding regions of CCMV RNA3 are also dispensable for RNA3 replication and for transcription of the subgenomic coat protein mRNA. To determine whether these noncoding sequences are required for systemic infection, a series of 5' and intercistronic deletions in RNA3 were tested for their effects on the infection of cowpea plants, a natural host of CCMV. The results refine the mapping of the subgenomic mRNA promoter and show that at least 144 bases in the 5' noncoding region and at least 125 bases in the intercistronic noncoding region of CCMV RNA3 are dispensable for systemic infection. For mutants with deletions within these regions, no differences were noted in the rate of infection spread, and the level of virus accumulation in systemically infected tissue 10-14 days postinoculation was 60-100% of wild type (wt). However, the largest viable intercistronic deletion transformed the nearly symptomless appearance of wt CCMV infections to an extensive, bright yellow chlorosis, showing that infection pathology can be altered by mutations with a regulatory rather than a protein coding character. In addition, neither 5' nor intercistronic deletion mutants competed effectively with wt CCMV in whole plant co-infection experiments; i.e., such mutants were not detectable in systemically infected tissue after co inoculation with wt CCMV. Thus, although substantial portions of both the 5' and the intercistronic noncoding regions of CCMV RNA3 are dispensable for individual systemic infection, these segments contribute to the competitive fitness of the virus and influence interaction with the host, as evidenced by symptom response. PMID- 1736533 TI - Characterization of the potyviral HC-pro autoproteolytic cleavage site. AB - The helper component-proteinase (HC-Pro) encoded by potyviruses functions to cleave the viral polyprotein by an autoproteolytic mechanism at the HC-Pro C terminus. This protein belongs to a group of viral cysteine-type proteinases and has been shown previously to catalyze proteolysis between a Gly-Gly dipeptide. The amino acid sequence requirements surrounding the HC-Pro C-terminal cleavage site of the tobacco etch virus polyprotein have been investigated using site directed mutagenesis and in vitro expression systems. A total of 51 polyprotein derivatives, each differing by the substitution of a single amino acid between the P5 and P2' positions, were tested for autoproteolytic activity. Substitutions of Tyr (P4), Val (P2), Gly (P1), and Gly (P1') were found to eliminate or nearly eliminate proteolysis. Substitutions of Thr (P5), Asn (P3), and Met (P2'), on the other hand, were permissive for proteolysis, although the apparent processing rates of some polyproteins containing these alterations were reduced. These results suggest that auto-recognition by HC-Pro involves the interaction of the enzymatic binding site with four amino acids surrounding the cleavage site. Comparison of the homologous sequences of five potyviral polyproteins revealed that the residues essential for processing are strictly conserved, whereas the nonessential residues are divergent. The relationship between HC-Pro and other viral and cellular cysteine-type proteinases is discussed. PMID- 1736534 TI - Characterization of a novel nuclear localization signal in the HTLV-I tax transactivator protein. AB - The Tax trans-activator protein of the type I human T-cell leukemia virus is expressed predominantly in the nuclei of cells. However, this viral trans activator is distinguished from most other nuclear proteins by the absence of a short highly basic nuclear localization signal. Previous mutational analyses of the tax gene revealed that many of the missense mutations involving the amino terminus of Tax resulted in a predominantly cytoplasmic pattern of expression. We now report that the amino terminal 48 residues of Tax comprise a functional nuclear localization signal as demonstrated by the ability of this region to retarget expression of a large cytoplasmic protein to the nucleus. PMID- 1736535 TI - Nonreplicating viral vectors as potential vaccines: recombinant canarypox virus expressing measles virus fusion (F) and hemagglutinin (HA) glycoproteins. AB - The development of canarypox virus (CPV) recombinants expressing the hemagglutinin (HA) and fusion (F) glycoproteins of measles virus (MV) is described. Inoculation of the CPV-MV recombinants into avian or nonavian tissue culture substrates led to the expression of authentic MVF and MVHA as determined by radioimmunoprecipitation and surface immunofluorescence. In contrast to avian derived tissue culture, no productive replication of the CPV recombinant was evident in tissue culture cells derived from nonavian origin. On inoculation of dogs, a species restricted for avipoxvirus replication, the recombinants elicited a protective immune response against a lethal canine distemper virus (CDV) challenge. The level of MV neutralizing antibodies and the level of protection induced against CDV challenge achieved by the host-restricted CPV vector were equivalent to that obtained by vaccinia virus vectors expressing the same MV antigens. PMID- 1736536 TI - The mass of the Sindbis virus nucleocapsid suggests it has T = 4 icosahedral symmetry. AB - The mass of the nucleocapsid of the alphavirus Sindbis was determined by scanning transmission electron microscopy. The nucleocapsid was found to have an average mass of 10.54 x 10(6) Da with the largest percentage of particles showing a mass of 10.7 to 10.9 x 10(6) Da. These data predict that the nucleocapsid contains 240 copies of protein and is a T = 4 icosahedron. PMID- 1736537 TI - Rapid sequence evolution of street rabies glycoprotein is related to the highly heterogeneous nature of the viral population. AB - The sequence of the glycoprotein gene of a street rabies virus was determined directly using fragments of a rabid dog brain after PCR amplification. Compared with that of the prototype strain CVS, this sequence displayed 10% divergence in overall amino acid composition. However only 6% divergence was noted in the ectodomain suggesting that structural constraints are exerted on this portion of the glycoprotein. A human strain isolated on cell culture from the saliva of a patient with clinical rabies had only five amino acid differences with the canine isolate, an indication of their close relatedness. These differences could have originated during transmission from dog to dog, or from dog to man, or during isolation on cell culture; they are nonetheless indicative of a genetic evolution of street rabies virus. This evolution was further evidenced by the selection of cell-adapted variants which displayed new amino acid substitutions in the glycoprotein. One of them concerned antigenic site III where arginine at position 333 was replaced by glutamine. As expected this substitution conferred resistance to a site IIIa monoclonal antibody (MAb), but surprisingly did not abolish neurovirulence for adult mice. However, a decrease in the neurovirulence of the cell-adapted variant in the presence of a site IIIa specific MAb was noted, suggesting that neurovirulence was due to a subpopulation neutralizable by the MAb. Simultaneous presence of both the parental and variant sequences was indeed evidenced in the brain of a mouse inoculated with the cell-adapted variant; during multiplication in the mouse brain, the frequency of the parental sequence rose from less than 10% to nearly 50%, indicating the selective advantage conferred by arginine 333 in nervous tissue. Altogether these results were suggestive of an intrinsic heterogeneity of street rabies virus. This heterogeneity was further demonstrated by the sequencing of molecular clones of the glycoprotein gene, which revealed that only one-third of the viral genomes present in the brain of a rabid dog had the consensus sequence. Two-thirds of the clones analyzed displayed from one to three amino acid substitutions. Such heterogeneous populations have been referred to as quasispecies, a concept which implies heterogeneous populations kept together in a dynamic equilibrium. This equilibrium could be rapidly displaced, giving the virus the capacity to adapt easily to new environmental conditions. PMID- 1736538 TI - Yeast killer virus transcription initiation in vitro. AB - Killer virions isolated from infected Saccharomyces cerevisiae cells contain an RNA polymerase activity which catalyzes the transcription in vitro of positive polarity RNAs from the L-A and M double-stranded RNA genomic segments of the virus. The RNA polymerase can initiate transcription in vitro with gamma-thio GTP, whose thiophosphate group is found on the 5' terminus of transcripts. Transcripts produced in vitro by the virion-associated RNA polymerase in the presence of 7mGpppG are significantly more active as translational templates than are transcripts produced in its absence. However, unlike Escherichia coli RNA polymerase transcripts from viral cDNA made in the presence of 7mGpppG, transcripts produced by viral RNA polymerase in the presence of 7mGpppG fail to bind to antibody against 7mG. PMID- 1736539 TI - Stability of p53 protein in rat cells transformed by various viral transforming genes. AB - To clarify the correlation between metabolic stabilization of p53 protein and cellular transformation, we transformed the normal rat cell line F2408 with various viral transforming genes and examined the expression and stability of p53 protein in these transformed cells by pulse-chase immunoprecipitation experiments. As expected, the level of p53 in the SV40-transformed rat cell line was higher than that in the normal cell line and its stability was also increased. In contrast, in cells transformed with the E7 and E6 genes of human papillomavirus type 16, the level and stability of p53 were similar to those in the normal cells. In cells transformed by the middle T or large T of polyomavirus, v-K-ras, and v-src, the levels and stabilities of p53 were also not elevated, although the level of p53 was increased in activated c-H-ras transformed cells without an increase in its stability. These results show that increased stability and expression of the p53 protein are not common events in viral transformation of the rat cell line. In addition, we demonstrated with a monoclonal antibody specific for the mutant form of p53 that cellular transformation by viral transforming genes does not involve mutational activation of p53 to an oncogenic form. PMID- 1736540 TI - Properties of a new virus belonging to nodaviridae found in larval striped jack (Pseudocaranx dentex) with nervous necrosis. AB - Spherical virus particles were purified from larval striped jack (Pseudocaranx dentex) with nervous necrosis. The virus consists of nonenveloped particles, about 25 nm in diameter, and contains two single-stranded, positive-sense RNA molecules with molecular weights of 1.01 x 10(6)Da (RNA 1) and 0.49 x 10(6)Da (RNA 2), respectively. The RNAs do not have poly(A) sequences at the 3' terminus. Virus structural proteins consist of two proteins with molecular weights of 42 and 40 kDa. When translated into cell-free extracts of rabbit reticulocytes, RNA 1 directed the synthesis of the 1a protein (100 kDa), whereas RNA 2 synthesized the 2a protein (42 kDa), which is probably the coat protein of the virus, and a polypeptide of 40 kDa which appears to be the processed form of the 42-kDa protein. Under electron microscopic observation, the virus particles were found in the tissues of the central nervous system of the affected larval striped jack. From morphological and biochemical properties of the virus, we identified this virus as a new member of the family of Nodaviridae and designated it striped jack nervous necrosis virus. PMID- 1736541 TI - Interferon-gamma-induced assembly block in the replication cycle of adenovirus 2: augmentation by tumour necrosis factor-alpha. AB - Replication of adenovirus 2 (Ad-2) is inhibited in A 549 cells pretreated with interferon-gamma (IFN-gamma). The antiviral effect is synergistically enhanced by the simultaneous presence of tumor necrosis factor-alpha (TNF-alpha) before infection. Under conditions of strong inhibition of virus progeny formation, viral DNA synthesis and [35S]methionine incorporation into most late viral proteins are only marginally impaired. Pulse chase experiments indicate a partial inhibition of processing of viral proteins. Viral proteins are not degraded and capsomeres accumulate in the inhibitor-treated cells. Capsid formation, on the other hand, is strongly inhibited in the cytokine-treated cells. The inhibition of Ad-2 replication in A 549 cells by IFN-gamma and TNF-alpha is caused, therefore, by a block in the maturation of Ad-2. PMID- 1736542 TI - Role of asparagine-linked glycosylation in human immunodeficiency virus type 1 transmembrane envelope function. AB - Transmembrane envelope protein (TM) residues 100, 105, and 128 of human immunodeficiency virus type 1 (HIV-1) strain HXB2 are potential sites for asparagine-linked oligosaccharide additions which are conserved among HIV-1 isolates, and all other lentivirus TM proteins. Site-specific mutants of each of the asparagine residues did not eliminate the ability of the virus to infect and replicate in CD4+ cells, but infectivity was reduced with all of these mutants, and syncytia induction was attenuated with two of these mutants. Studies of envelope expression of the mutant with the most severe defect demonstrated no significant effects on envelope protein synthesis, conformation, processing, multimerization, or release into the culture medium, suggesting that N-linked oligosaccharides are important in the specific fusion activity of TM. PMID- 1736543 TI - Sensitive method for identification of minor hepatitis B mutant viruses. AB - There is increasing evidence for selection of hepatitis B virus (HBV) mutants during the natural course of infection, after immunization, and during interferon therapy. These mutants can prolong viral persistence, escape immune-mediated elimination, and influence the clinical sequelae of infection. Here we describe a sensitive and reliable method that allows detection of HBV mutants within a heterogeneous virus population. The method consists of amplification of HBV DNA with vector-HBV hybrid primers, efficient and enzyme-free cloning of the amplified DNA fragment, identification by hybridization with synthetic oligonucleotide probes, and sequencing of the cloned DNA fragments. We demonstrate that up to 10(5) HBV DNA fragments can be obtained in cloned form from a single amplification reaction, the ratio of HBV pre-C "wild-type" and mutant sequences of heterogeneous populations can be determined, and very minor virus subpopulations can be identified. The method can be applied to other viral or nonviral nucleic acid sequence variation studies and should help to resolve the role of mutant and wild-type viruses in pathogenesis and the forces driving their selection. PMID- 1736544 TI - Effect of myristoylation on p27 nef subcellular distribution and suppression of HIV-LTR transcription. AB - The effect of myristoylation on p27nef subcellular distribution and suppression of HIV-1 transcription was examined by transfecting COS-7 cells with plasmids expressing either myristoylated (pSVnef) or nonmyristolyated p27nef (pSVnefala2). Similar levels of myristoylated and nonmyristoylated p27nef were expressed with only the product of the pSVnef plasmid being myristoylated. Immuno-histochemical microscopy and radioimmunoprecipitation revealed myristolyated p27nef only in the membrane fraction while nonmyristolyated p27nef was found distributed between the nucleus and the cytosol fractions. The effect of myristoylation on p27nef suppression of HIV LTR controlled transcription was examined in transient transfected COS cells and in CEM human T-cell clones consituitively expressing either myristolyated or nonmyristolyated p27nef by cotransfecting with a chloramphenicol acetyltransferase (CAT) plasmid under control of the HIV-1 LTR. In both systems, myristoylated p27nef exhibited a 13- to 18-fold inhibition of basal CAT activity while the nonmyristolyated mutant and the same plasmid carrying the nef gene in a reverse orientation inhibited CAT activity one- to two fold. These results confirm the cytoplasmic membrane localization of p27nef and establish that its subcellular targeting is dependent on covalently attached myristate. The data also provide further evidence that p27nef acts as a transcriptional suppressor and establishes for the first time that myristolyation is required for the full manifestation of this effect. PMID- 1736545 TI - Induction of ribonucleotide reductase activity in cells infected with African swine fever virus. AB - Infection of Vero cells with African swine fever virus (ASFV) resulted in a marked increase in ribonucleotide reductase activity. The induction of ribonucleotide reductase was detected early after infection and was proportional to the multiplicity of infection. Inhibition of viral DNA replication did not affect the induction of the enzyme. Several characteristics could distinguish the virus-induced from the normal cell enzyme. ASFV-induced ribonucleotide reductase was inhibited by magnesium, was more strongly inhibited by hydroxyurea, and had a fourfold lower Km. The virus-induced enzyme was inhibited by deoxyribonucleoside triphosphates and by ATP. The isolation of hydroxyurea-resistant ASFV mutants provided genetic evidence for the viral origin of the induced ribonucleotide reductase. The resistance to hydroxyurea was due to a threefold overproduction of ribonucleotide reductase, as compared to enzyme induction by wild-type ASFV. Hydroxyurea had similar effect in vitro on ribonucleotide reductases induced by wild-type or mutant virus. The gene for the small subunit of the viral enzyme was mapped within a 2.3-kb fragment by hybridization with an oligonucleotide probe designed from a conserved aminoacid sequence of eukaryotic and viral ribonucleotide reductases. PMID- 1736546 TI - Molecular analysis of the trans-activating IE-2 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus. AB - A second immediate early (IE) regulatory gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) has been identified. The IE-2 gene which is homologous to the IE-N gene of Autographa californica MNPV was mapped to the HindIII A fragment of OpMNPV between 0.41 to 1.37 map units. The IE-2 gene codes for a predicted protein of 45,640 Da and analysis of the amino acid sequence shows that the protein has a highly basic amino terminal domain and a cysteine-rich domain that is similar to a zinc finger motif that is also found in the baculovirus proteins GC30 and PE-38. The IE-2 gene is expressed as a 1.3-kb transcript that was detectable by 0.5 hr postinfection (hr p.i.), reached maximum steady state levels by 6 hr p.i., and declined slightly by 48 hr p.i. Cis-acting 5' regulatory sequences were analyzed by deletion analysis of the IE-2 promoter linked to the reporter gene chloramphenicol acetyl transferase. Maximum expression was obtained when the IE-2 promoter contained sequence 275 bp upstream from the transcriptional start site. trans-Activation analysis revealed that IE-2 trans-activated the IE-1 promoter and in addition appeared to be autoregulatory. PMID- 1736547 TI - Tandemly repeated sequence at the 3' end of the IE-2 gene of the baculovirus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus is an enhancer element. AB - An enhancer element was identified in the virus Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) that is located adjacent to the 3' end of the IE-2 gene and 5' to an open reading frame that codes for a predicted protein that has 37% homology to the AcMNPV PE-38 gene. The OpMNPV enhancer (OpE) consists of a 66-bp element that is tandemly repeated partially or completely 12 times. The OpE sequences were shown to increase gene expression from the Autographa californica MNPV delayed early p39 promoter independently of position or orientation, and were also shown to increase expression from the promoter of the OpMNPV immediate early gene, IE-2. Sequences homologous to the OpE sequences were mapped by Southern blot hybridization to four additional locations around the OpMNPV genome. This indicates that OpMNPV is similar to other baculoviruses such as AcMNPV, Lymantria dispar MNPV, and Choristoneura fumiferana MNPV that have homologous regions in several locations in the genome. PMID- 1736548 TI - High-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy. AB - We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p less than 0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy. PMID- 1736549 TI - Glucocorticoid receptor and inhibition of 3-O-methyl-D-glucose uptake by glucocorticoids in peripheral blood leukocytes from normal humans: correlation between receptor level and hormone effect in vitro. AB - We have measured the glucocorticoid receptor concentration in mononuclear and polymorphonuclear leukocytes, both of which were isolated from peripheral blood from ten healthy male volunteers. In parallel, the inhibitory effect of dexamethasone on 3-O-methyl-D-glucose uptake was assayed in the corresponding mononuclear leukocytes. The glucocorticoid receptor levels in mononuclear leukocytes correlated with those in polymorphonuclear leukocytes, and there was a linear relationship between the cellular glucocorticoid receptor levels and glucocorticoid-mediated inhibition of the uptake of 3-O-methyl-D-glucose in mononuclear leukocytes. When mononuclear leukocytes were incubated in the presence of 8-bromo-cAMP, cellular glucocorticoid receptor levels increased and a more pronounced inhibitory effect of dexamethasone was observed on the transport of 3-O-methyl-D-glucose. We conclude that the cellular glucocorticoid receptor levels in peripheral blood leukocytes reflect in vitro responsiveness to glucocorticoids in mononuclear leukocytes from healthy males, and that the individual responsiveness may alter upon changes in the cellular levels of glucocorticoid receptor. PMID- 1736550 TI - Clinical heterogeneity of 21-hydroxylase deficiency of sibs with identical 21 hydroxylase genes. AB - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder with different clinical manifestations, that results from mutations in the P 450(c21) gene. Direct sequence analysis of P-450(c21) genes in a family demonstrates that patients with different clinical forms of congenital adrenal hyperplasia can have identical P-450(c21) genes, suggesting that other effects play a role in developing the different clinical forms. PMID- 1736551 TI - Progressive and concurrent deterioration of vagus-stimulated and hypoglycemia induced glucagon secretion in streptozotocin-diabetic rats. AB - The effects of left cervical vagus nerve stimulation on glucagon secretion were studied in streptozotocin-diabetic and age-matched control adult male rats. At two-week intervals, after the induction of streptozotocin-diabetes, streptozotocin-diabetic and age-matched control rats were anesthetized with chloral hydrate (350 mg/kg, ip). Left cervical vagus nerves were electrically stimulated via a Grass stimulator with 5-volt monophasic pulses of 3 msec duration at a frequency of 20 Hz for 1, 2, and 4 min. Arginine-induced glucagon secretion was also determined. Vagus nerve-stimulated (2 and 4 min) glucagon secretion deteriorated as the duration of streptozotocin-diabetes increased. Glucagon secretion in response to vagus nerve stimulation was virtually absent by 12 weeks of streptozotocin-diabetes. However, arginine-induced glucagon secretion was unaffected. Subsequent experiments showed that the defect in glucagon secretion from vagal stimulation occurred concurrently with that seen from insulin-induced hypoglycemia. These results indicate that the impaired hypoglycemia-induced glucagon secretion in long-term streptozotocin-diabetic rats may be correlated with the deterioration of the parasympathetic nervous system transmission in streptozotocin-diabetes. PMID- 1736552 TI - The plateau phase rat goiter contains a sub-population of TSH-responsive follicular cells capable of proliferation following transplantation. AB - In the rat, chronic TSH stimulation leads to self-limited thyroid hyperplasia, goitrogenesis, and TSH-responsive thyroid tumors. The current studies were aimed at clarifying the mechanism by which hormone-responsive, proliferating follicular cells arise in quiescent plateau phase rat goiters. Enzymatically monodispersed rat thyrocytes from early plateau phase and involuting goiters were analyzed for the capacity to form thyroid follicular units after transplantation into syngeneic recipients. Goiters induced with two different regimens contained substantial numbers of cells capable of proliferating into functioning thyroid follicular tissue after transplantation. The clonogenic fractions of cells from goiters induced by 3-amino-1,2,4-triazole or KClO4/Remington low iodine diet were significantly lower than that of cells from control glands. Furthermore, the clonogenic fraction of cells from the KClO4 goiters was also found to be significantly less than that of cells from aminotriazole goiters despite similar TSH levels in the cell donors. The hormone responsiveness of the clonogenic goiter cells and the histological appearance and functional capacity of the thyroid tissue which arose after grafting were indistinguishable from controls. We conclude that the capacity to clonally proliferate into follicular units is a specific trait which characterizes a unique subset of follicular cells and speculate that the hormone-responsive tumors which typically appear in the chronically stimulated rat thyroid originate from cells within this subset. PMID- 1736553 TI - Performance Based Development Systems (PDBS). Interview by Eve Henderson. PMID- 1736554 TI - Writing a research proposal for AFNR: how to fill out AFNR-4. PMID- 1736556 TI - Memories of Jenny. PMID- 1736555 TI - A story of hope and courage. Interview by Darlene Konduc. PMID- 1736557 TI - Your last days. PMID- 1736558 TI - Is nursing information significant in determining resource allocation? PMID- 1736559 TI - Specialization in nursing: its history and its future. AB - Advances in knowledge and technology in the health care field has made specialization in nursing inevitable. The history of specialization points to a need for standardizing specialty nursing education. The options for standardizing specialization include post-RN certification, incorporating specialization into basic nursing education, or allowing specialization only at the masters level. The pathway for specialization must be clearly defined with recognition for specialized nursing practice to keep nurses at the bedside and promote job satisfaction. PMID- 1736560 TI - Coronary risk factors and the severity of angiographic coronary artery disease in members of high-risk pedigrees. AB - Affected members of early coronary pedigrees in Utah are at markedly increased risk for the development of clinical coronary heart disease (CHD). The relationship between the presence of coronary risk factors and the severity of angiographic coronary artery disease (CAD) in 53 members of high-risk Utah pedigrees was examined. Mean angiographic severity scores were higher in familial hypercholesterolemia or familial low high-density lipoprotein cholesterol (HDL-C) pedigrees than in type III hyperlipidemia or familial combined hyperlipidemia pedigrees. One sibling pair with hyperhomocyst(e)inemia had the highest mean angiographic severity scores. Clinical CHD (p less than 0.0001), increasing low density lipoprotein cholesterol (LDL-C) (p = 0.0107), and decreasing HDL-C (p = 0.0068) were significant predictors of angiographic CAD severity. There appeared to be an interaction between gender and body mass index but not between gender and serum lipids in the prediction of angiographic CAD severity. Results of the present study in members of high-risk Utah pedigrees are consistent with results from other angiographic studies in non-high-risk persons. Of particular interest is the suggested independent predictive value of low HDL-C for angiographic CAD severity in members of high-risk pedigrees. PMID- 1736561 TI - Oxidative status of lipoproteins in coronary disease patients. AB - Oxidized low-density lipoprotein (LDL) may play an important role in atherogenesis. The oxidative status of isolated LDL and very low-density lipoprotein (VLDL) were investigated in 23 patients with proven coronary disease and in 23 healthy asymptomatic control subjects. Oxidized cholesterol (4 cholesten-3-one and 20 alpha-OH cholesterol) was identified in LDL and VLDL from both groups. The content of cholesterol and 4-cholesten-3-one in LDL from patients was significantly increased in comparison with values from the control subjects. Lipid peroxidation, as assessed by malondialdehyde (MDA) formation, was barely detectable in native LDL and VLDL from the two groups. However, after incubation with a free radical-producing system, MDA levels in LDL from patients were significantly higher than those in control subjects. Lysine reactivity in LDL after incubation with an oxidizing agent, CuSO4, was similar between groups. However, lysine reactivity to CuSO4 in VLDL from patients was less than that in control subjects. Our results suggest that LDL levels from patients with coronary disease have an elevated oxidized cholesterol content and are more susceptible to peroxidative modification. Conversely, the LDL apoprotein does not appear to have been oxidatively modified in these patients. The data are consistent with a role for oxidized LDL in coronary artery disease and indicate that the LDL lipid may be an important oxidation site. PMID- 1736562 TI - Inhibition of platelet aggregation by prostacyclin is attenuated after exercise in patients with angina pectoris. AB - We tested whether alteration of platelet sensitivity to prostacyclin (PGI2) is involved in the activation of platelets induced by exercise in patients with stable angina. Twenty patients and 20 control subjects underwent treadmill testing. Blood samples were obtained before and immediately after exercise for plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha (6kP) assays and platelet aggregation studies. Dose-response curves for platelet aggregation to collagen were obtained in the presence and absence of 1 nmol/L PGI2 to quantify the antiaggregation effects of PGI2. At rest, platelet aggregation by collagen was enhanced in the patients. However, platelets were more sensitive to exogenous PGI2, apparently associated with lower plasma 6kP levels in the patients. After exercise, plasma TXB2 levels increased in the patients but not in the control subjects. Plasma 6kP levels remained unchanged and platelet sensitivity to PGI2 decreased in the patients whereas these values increased in the control subjects. The exercise-induced changes in platelet sensitivity to PGI2 correlated with those of platelet adenylate cyclase activity in response to 1 nmol/L PGI2 (r = 0.787, p less than 0.01). Thus impaired sensitivity of platelets to PGI2, in addition to the reduced response of prostanoid secretion, might be relevant to the platelet activation associated with exercise in patients with stable angina. PMID- 1736563 TI - Differences in plasma beta-endorphin and bradykinin levels between patients with painless or with painful myocardial ischemia. AB - To verify whether plasma beta-endorphin and bradykinin affects the pathophysiology of myocardial ischemia and the perception of cardiac pain, 35 patients with coronary artery disease were subjected to treadmill testing and 48 hour Holter ECG monitoring to measure their pain thresholds. Patients were divided into two groups during exercise testing: group 1 (N = 19) who had ST segment depression, and group 2 (N = 16), who had chest pain. Both groups were then compared with 12 age-matched control subjects. Pain thresholds were measured after Holter ECG monitoring, and blood samples were drawn before and immediately after exercise. No statistical differences were noted between groups 1 and 2 with regard to the severity of myocardial ischemia as assessed by ST segment depression or exercise tolerance time. The frequency of the episodes of silent myocardial ischemia in group 1 was found to be significantly (p less than 0.05) higher than that in group 2. The duration of the episodes of silent myocardial ischemia in group 1 was 41.9 minutes (range 3 to 343 minutes), which was significantly (p less than 0.05) longer than that in group 2 (11.5 minutes; range 0 to 74). The pain threshold in group 1 was a statistically (p less than 0.05) higher value than that in group 2. Although the resting plasma beta-endorphin level in group 1 was not statistically significantly different from values in either group 2 or the control group, during exercise the plasma beta-endorphin levels in both group 1 and the control group were significantly (p less than 0.05) elevated in comparison with their resting levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736564 TI - Efficacy of three-channel ambulatory electrocardiographic monitoring for the detection of myocardial ischemia. AB - The recognition of silent myocardial ischemia (SMI) has been demonstrated to have important clinical relevance. Two-channel ambulatory (Holter) electrocardiographic recording is a commonly utilized method for detecting transient electrocardiographic ST segment changes representative of SMI. It has been suggested that the analysis of two channels alone may not adequately detect SMI. We therefore evaluated the diagnostic yield of three channels using a three channel electrocardiographic monitoring device in 46 consecutive patients (age 61 +/- 9 years) undergoing percutaneous transluminal coronary angioplasty of an isolated single-vessel stenosis. Modified bipolar chest leads V2, V5, and AVF (CM V2, CM-V5, and CS-AVF) were utilized for analysis. The percent detection of ST segment changes from various combinations of two-lead recordings were compared to the total three leads, and an absolute transient ST segment shift (STSS) of greater than or equal to 1 mm during balloon inflation was considered as evidence of myocardial ischemia. One patient was excluded because of the need for ventricular pacing during balloon inflation. A total of 33 of 45 patients had STSS in all three leads (percent detection = 73%), while 32 (71%) had STSS in the two-lead grouping with the highest diagnostic yield (CM-V2/CM-V5; p = ns). Of the various two-lead combinations studied, leads CM-V2 and CM-V5 provided the best lead set overall for the detection of ischemic STSS. Three-channel ambulatory electrocardiographic recording only marginally improves upon the detection of ischemia when compared with standard (CM-V2/CM-V5 or CM-V5/CS-AVF) two-channel ambulatory electrocardiographic recordings. PMID- 1736565 TI - Prognostic value of dipyridamole thallium-201 scintigraphy in patients with stable chest pain. AB - The usefulness of dipyridamole testing with planar thallium-201 scintigraphy for assessing risk of subsequent cardiac events was evaluated in 373 patients with stable chest pain. Follow-up information was complete in 362 patients (mean age 64 +/- 9 years). During an average follow-up period of 18 months, cardiac events occurred in 59 patients--unstable angina in 27, nonfatal acute myocardial infarction in 11, and death from cardiac causes in 21. A history of previous myocardial infarction, congestive heart failure, or coronary bypass surgery before the study, or the presence of an abnormal scan or one with a fixed perfusion defect was associated with a significantly increased frequency of subsequent cardiac events (p less than 0.05). However, the presence of a reversible perfusion defect was not associated with increased risk (p = 0.1872). Stepwise logistic regression showed that a history of coronary artery bypass surgery before the study and the presence of a fixed perfusion defect were the only variables with independent predictive value for occurrence of a subsequent cardiac event (p less than 0.05). Survival analysis revealed a significantly increased cardiac event rate in patients with abnormal scans compared with those with normal scans over a 30-month follow-up period (p less than 0.01). We conclude that dipyridamole testing with thallium-201 scintigraphy can provide prognostic information concerning risk of future cardiac events in patients with stable chest pain. The presence of a fixed perfusion defect in particular identifies patients at increased risk. PMID- 1736566 TI - The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group. AB - The prognostic value of silent ischemia during a symptom-limited predischarge exercise test (ET) was evaluated in 740 men after an episode of unstable angina or non-Q wave myocardial infarction. The 51% of patients with ST depression at the ET had a higher rate of myocardial infarction or death after 1 year (18%) compared with those without ST depression (9%; p less than 0.01). This increased risk was not influenced by the presence or absence of pain at the ET: 18.3% in patients with painful ischemia compared with 18.1% in patients with silent ischemia. However, ST depression combined with pain at the ET predicted a higher incidence of class III or IV angina at follow-up (43.9% compared with 16.7% in the group with asymptomatic ST depression; p less than 0.001). Because revascularization in addition to alleviating symptoms also enhances the prognosis in certain groups of patients, selections for coronary angiography and possible revascularization should not be made only on the basis of symptoms but also on the presence of myocardial ischemia, whether symptomatic or not. PMID- 1736567 TI - The effects of intravenous infusions of selective adenosine A1-receptor and A2 receptor agonists on myocardial reperfusion injury. AB - To determine the efficacy of very low doses of adenosine on myocardial reperfusion injury and whether its effect is receptor mediated, 78 rabbits underwent 30 minutes of left circumflex artery occlusion and 48 hours of reperfusion. Animals were randomly assigned to receive one of three doses of adenosine, cyclopentyladenosine (a selective A1-receptor agonist), or CGS 21680C (a selective A2-receptor agonist). The drugs were infused for 65 minutes beginning 5 minutes before reperfusion. A significant reduction in histologically determined infarct size was noted with all three doses of adenosine, intermediate and low doses of the A1-receptor agonist (cyclopentyladenosine), and high and intermediate doses of the A2-receptor agonist (CGS 21680C). Furthermore, all three adenosine receptor agonists afforded similar degrees of protection. Results of this study demonstrate that intravenous infusions of very low doses of adenosine significantly enhance myocardial salvage and this protection is receptor mediated. Furthermore, the administration of the A1-receptor agonist would be clinically appealing, since it would avoid the potential side effects associated with activation of A2 receptors. PMID- 1736568 TI - Reduction of reperfusion injury with preoperative rapid intravenous infusion of taurine during myocardial revascularization. AB - To assess a possible free-radical scavenging action of taurine during coronary artery bypass grafting, 12 patients were randomly divided into two equal groups. One to 3 hours before surgery, they received a rapid intravenous infusion of either placebo (group 1) or taurine (5 gm) (group 2). During surgery, biopsy samples were taken before ischemia (preischemic samples) and after 10 minutes of reperfusion (reperfusion samples). Lipoperoxidation was determined by hydroperoxide-initiated chemiluminescence of heart homogenates, and myocardial cell damage was assessed by electron microscopy. The values for chemiluminescence in preischemic and reperfusion samples from group 1 were 7500 +/- 1600 and 18,600 +/- 4600 cpm/mg of protein, respectively (p less than 0.03). This difference was not observed in group 2 where the values were 10,050 +/- 2700 and 11,800 +/- 4200 cpm/mg of protein, for preischemic and reperfusion samples, respectively. The number of severely damaged mitochondria (grades 3 and 4) in reperfusion samples from group 1 increased significantly compared to preischemic samples (25 +/- 8% vs 12 +/- 3%, p less than 0.01). Conversely no differences were observed between the number of severely damaged mitochondria in reperfusion and preischemic samples from group 2 (8 +/- 3% vs 8 +/- 2%). The number of damaged and necrotic myocytes increased in group 1 after reperfusion from 22 +/- 9% to 34 +/- 10% (p less than 0.03) and from 10 +/- 7% to 26 +/- 20% (p = NS), respectively. No changes were observed between reperfusion and preischemic samples in group 2. Treatment with taurine seems to reduce lipoperoxidation and decrease cell damage at the time of reperfusion. PMID- 1736569 TI - The transient nature of the effect of ischemic preconditioning on myocardial infarct size and ventricular arrhythmia. AB - We sought to determine whether short periods of preconditioning ischemia limited infarct size in a model of low coronary collateral flow and whether the effects of preconditioning were transient or long-lasting. Rats underwent 90 minutes of coronary occlusion followed by reperfusion. In one group, the rats were preconditioned by three 3-minute occlusions, each separated by 5 minutes of reperfusion. The size of the myocardial infarcts were smaller in the preconditioned group (24.9 +/- 7.8% of the risk zone developed necrosis) versus the nonpreconditioned group (60.7 +/- 5.3%, p less than 0.01). In addition, the incidence of ventricular arrhythmias was reduced by preconditioning. However, when there was a delay of 1 hour or more between the brief episodes of preconditioning and the longer 90-minute occlusion, the beneficial effects of preconditioning were lost. Thus preconditioning reduced the volume of myocardium infarcted and the incidence of ventricular arrhythmias during a subsequent period of prolonged ischemia; however, these beneficial effects were transient. PMID- 1736570 TI - Use of rapid serial sampling of creatine kinase MB for very early detection of myocardial infarction in patients with acute chest pain. AB - To determine how early myocardial infarction can be detected, serial creatine kinase MB concentrations were sampled in 313 patients during triage of acute (less than 12 hours) chest pain. Serum was sampled on hospital arrival (baseline) and hourly for 3 hours (total of four samples). Creatine kinase MB concentrations were subsequently analyzed for their ability to detect infarction. Infarction was present in 70 patients (22%) and was diagnosable from the index electrocardiograms in 27 of these (39%). Sensitivity and specificity for detection of infarction were 76% and 72%, respectively, as determined from baseline MB values only and increased with each additional sample to a maximum of 92% and 96%, respectively, in all four samples. Analysis of two serum samples taken 2 hours apart showed a sensitivity of 94% and a specificity of 91%. If these results are confirmed, improved initial diagnostic accuracy with this rapid assay technique in acute chest pain may (1) conserve resources when initial suspicion of infarction is low, (2) identify patients with infarction appropriate for early intervention, and (3) avoid premature hospital discharge of patients with infarction. PMID- 1736571 TI - Stress-induced ST segment shift in leads V3R and V4R after acute myocardial infarction. AB - A total of 107 patients with acute myocardial infarction underwent a dobutamine stress test and received increasing doses of the drug (5, 10, 15, 20, and up to 40 micrograms/kg/min). Coronary angiography was performed within the first month. The 12 conventional ECG leads plus the right chest leads V3R and V4R were recorded under basal conditions and after each dose of dobutamine. In 51 patients (group A) there was an ST shift greater than or equal to 0.5 mm in the right chest leads, with two different patterns: rightward (V2 less than V1 less than V3R V less than V4R) (n = 26) and leftward (V2 less than V1 less than V3R greater than V4R) (n = 25). In 56 patients (group B) no ST shift in the right chest leads was induced. An ST segment elevation greater than or equal to 0.5 mm in V4R was 43% sensitive and 86% specific for the detection of proximal right coronary artery disease. Four subgroups were established in group A: A1R, rightward ST elevation (n = 23); A1L, leftward ST elevation (n = 12); A2R, rightward ST depression (n = 3); and A2L, leftward ST depression (n = 13). Group A1R had predominantly inferior infarcts and right coronary artery stenoses, group A1L had predominantly anterior infarcts and left anterior descending coronary stenoses, and group A2L had posteroinferior infarcts and right or left circumflex stenoses, all of them with low sensitivity (less than 50%) and high specificity (greater than 87%) for a such diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736572 TI - The RSR' complex not related to right bundle branch block: diagnostic value as a sign of myocardial infarction scar. AB - An abnormal electrocardiographic (ECG) wave pattern--the RSR' complex--associated with a wide QRS (greater than or equal to 110 msec), unrelated to right bundle branch block (RBBB) or left bundle branch block (LBBB) was identified in 26 patients with old myocardial infarction. Patients were assigned to three groups: in group I (n = 13) the RSR' was present in the precordial leads; in group II (n = 9) the RSR' was present in the inferior limb leads; and in group III (n = 4) the RSR' was present in both. For each patient a severe segmental wall motion abnormality (akinetic in 16 and dyskinetic in 10 patients) consistent with myocardial infarction scar tissue was detected using the equilibrium radionuclide angiocardiogram (n = 24) and the two-dimensional echocardiogram (n = 2). The abnormal RSR' complex arises from a terminal conduction delay (dissimilar to either RBBB or LBBB using the vectorcardiogram) of left ventricular (LV) depolarization within impaired tissue surrounding the infarct scar. This study suggests that the RSR' complex, a unique mural conduction defect, although poorly sensitive has specific diagnostic value and reliability as a sign of myocardial infarction scar. PMID- 1736573 TI - Compensatory and noncompensatory left ventricular dilatation after myocardial infarction: time course and hemodynamic consequences at rest and during exercise. AB - Survival after myocardial infarction decreases with left ventricular dilatation, although dilatation at 4 weeks was found to be compensatory. To study this apparent discrepancy, prospective simultaneous volume and hemodynamic measurements at rest were extended in 39 patients with small and 37 with large myocardial infarctions from 4 (range 2 to 6) days and 4 (range 3 to 5) weeks to 6 (range 5 to 8) months after myocardial infarction and were repeated during exercise. In small myocardial infarctions, end-diastolic volume index (EDVI) decreased from 4 days to 6 months; ejection fraction, stroke volume index (SVI), and end-systolic volume index (ESVI) remained unchanged. SVI increased during exercise at 4 weeks and at 6 months. In large myocardial infarctions (n = 37) ESVI (4 days = 38 +/- 3, 4 weeks = 47 +/- 3,* 6 months = 52 +/- 3*; *p less than 0.05 versus 4 days) and EDVI (4 days = 72 +/- 3, 4 weeks = 86 +/- 5,* 6 months = 92 +/- 5* ; *p less than 0.05 versus 4 days and p less than 0.05 versus 4 weeks) increased at constant wedge pressure. SVI remained unchanged beyond 4 weeks (4 days = 35 +/- 2, 4 weeks = 42 +/- 2*, 6 months = 42 +/- 2*; *p less than 0.05 versus 4 days) and increased during exercise at 4 weeks (rest = 45 +/- 2, exercise = 55 +/- 3; p less than 0.05) but not at 6 months (rest = 42 +/- 3, exercise = 45 +/- 3; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736574 TI - Clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring (VEST): validation and study of the effects of nitroglycerin and nifedipine in patients with and without coronary artery disease. AB - Global left ventricular function and ECGs were continuously monitored by radionuclide ambulatory ventricular function monitoring (VEST) and validated against multigated blood pool analysis (MUGA) and left ventriculography in 26 subjects (study 1). Ejection fraction by VEST (Y) showed good correlation with Y = 5.5 +/- 0.79 X (r = 0.91), Y = 1.7 +/- 0.86 X' (r = 0.91), and Y = 11.6 + 0.68 X" (r = 0.82) to sitting and supine MUGA and left ventriculography, respectively. In study 2 left ventricular function and ECGs were evaluated at rest and during exercise without any drug (control), with nitroglycerin, and with nifedipine in 21 patients with coronary disease (group I) and six normal subjects (group II). In group I abnormal ejection fraction responses (exercise increase less than or equal to 6%) during the control exercise period were found in 15 patients (71%), ST segment abnormalities in seven (33%), and chest pain in four (18%). Control exercise increased end-diastolic volume (100 to 112 +/- 8%) and end-systolic volume (53 +/- 15% to 63 +/- 22%) and decreased the ejection fraction (47 +/- 15% to 43 +/- 21%). The ejection fraction during exercise increased after nitroglycerin (50 +/- 22%) or nifedipine (54 +/- 21%) (p less than 0.05). In group II the ejection fraction was unchanged between rest and exercise with or without nitroglycerin or nifedipine. Thus combined radionuclide and ECG monitoring by VEST could detect changes in left ventricular function at rest and during exercise over a prolonged period and demonstrated that nitroglycerin and nifedipine improved cardiac function in the ischemic setting with an increased ejection fraction in the upright position. PMID- 1736575 TI - Comparison of gray-scale and B-color ultrasound images in evaluating left ventricular systolic function in coronary artery disease. AB - To confirm whether or not echocardiographic B-color images (temperature, magenta, rainbow) are superior to ordinary gray-scale images, 62 coronary artery disease (CAD) patients (42 men and 20 women) underwent gray-scale and B-color echocardiography and cineangiography within 24 hours. Left ventricular (LV) volume was derived from angiography using the single-plane area-length method and was derived from echocardiography using single-plane modified Simpson's formula. In predicting angiographic volume, the correlations between B-color images and angiography were similar to that between the gray-scale image and angiography. In evaluating LV ejection fraction, the correlation coefficients between B-color images and angiography (temperature r = 0.93, magenta r = 0.93, rainbow r = 0.92) were slightly higher than that between the gray-scale image and angiography (r = 0.85) (p less than 0.05). We conclude that B-color images yield estimates of LV volumes that are of similar accuracy to gray-scale images in patients with CAD. PMID- 1736576 TI - Hypotension during dobutamine stress echocardiography: initial description and clinical relevance. AB - Hypotension during exercise treadmill testing is correlated with the presence of coronary artery disease, its severity, and prognosis. The importance of hypotension during dobutamine stress testing has not been previously reported to our knowledge. We reviewed 43 cases of hypotension occurring in 42 patients out of a total of 116 consecutive stress dobutamine echocardiographic procedures performed in a total of 112 patients. Of the 42 patients with hypotension, 20 underwent cardiac catheterization. Regional wall motion abnormalities induced by dobutamine infusion were found in 13 of these patients, all of whom had significant (greater than or equal to 70% diameter reduction) coronary artery disease. The remaining seven patients without regional wall motion abnormalities did not have significant coronary artery disease at catheterization. Of the remaining 22 patients with dobutamine-induced hypotension, 20 had no induced regional wall motion abnormalities, were not catheterized, and were followed clinically. None of these patients had a cardiac event during a mean follow-up period of 11.5 months. We conclude that hypotension during dobutamine stress echocardiography in the absence of regional wall motion abnormalities does not indicate significant coronary artery disease or portend an adverse prognosis. PMID- 1736577 TI - Flecainide therapy in patients treated for supraventricular tachycardia with near normal left ventricular function. AB - Concerns about the safety and efficacy of class IC antiarrhythmic agents have arisen as a result of the recent CAST data. We reviewed records of 175 consecutive patients treated with flecainide between July 1, 1988 and July 5, 1989. One hundred ten patients with normal or mildly impaired left ventricular function and symptomatic supraventricular arrhythmias were identified. Follow-up data were obtained on 102 patients for a mean of 14 months. The average duration of flecainide therapy was 13 months. Tachyarrhythmias treated included atrial fibrillation/flutter, atrioventricular reentry, and atrioventricular nodal reentry. Flecainide provided effective antiarrhythmic therapy in 62% of the patients and was discontinued in 38% of the patients. Left atrial size did not predict treatment failure. Two patients developed proarrhythmic events (nonsustained ventricular tachycardia). There were no deaths during the follow-up period. In conclusion, flecainide provides safe and effective therapy for supraventricular tachyarrhythmias in patients with normal or mildly impaired left ventricular function. PMID- 1736578 TI - Optimal late potential criteria for reducing false positive signal-averaged electrocardiograms. AB - The purposes of this study were to determine for signal-averaged electrocardiograms in normal subjects: (1) the incidence of false positives for various filter frequencies and late potential criteria and (2) reproducibility over time. In 46 normal volunteers, the QRS vector magnitude was bidirectionally high-pass filtered at 25, 40, and 100 Hz. As high-pass filter frequency increased, QRS duration decreased from 98 +/- 9 to 92 +/- 9 msec (p less than 0.0001), terminal QRS root mean square voltage decreased from 60 +/- 41 to 14 +/- 9 microV (p less than 0.0001), and terminal QRS low amplitude signal duration increased from 27 +/- 7 to 41 +/- 14 msec (p less than 0.0001). For individual parameters, the incidence of false positive tests ranged from 2% to 41%, whereas there were no false positive tests for the combination of abnormal QRS duration plus either root mean square voltage or low amplitude signal duration. Measurements were repeated after 6.4 +/- 0.3 months in 26 subjects and were highly reproducible at all filter settings. The potentially high incidence of false positive tests with some criteria has important implications for the use of signal-averaged electrocardiography as a screening test in patient populations with various arrhythmia risks. PMID- 1736579 TI - Transesophageal low-energy synchronous cardioversion of atrial flutter/fibrillation in the dog. AB - The purpose of this study was to determine the feasibility and efficacy of terminating atrial flutter/fibrillation using low-energy synchronous shocks delivered through a transesophageal catheter in dogs with talc-induced pericarditis. Atrial flutter/fibrillation was induced by employing the pulse train method. The minimum effective cardioversion energy level was compared for three different methods--method A, delivery between a distal esophageal electrode and a proximal esophageal electrode; method B, delivery of shocks through a distal esophageal electrode and a plate placed on the chest; method C, transthoracic cardioversion. The minimum effective cardioversion energy level did not differ significantly between methods A and B (1.30 +/- 0.46 joules versus 1.29 +/- 0.35 joules). Transesophageal cardioversion decreased the defibrillation threshold three- to fourfold from that of conventional transthoracic cardioversion. There were no complications of heart block, ventricular fibrillation, or any pathologic evidence of esophageal injury. Thus transesophageal low-energy synchronous cardioversion is considered a feasible and effective method for the treatment of atrial flutter/fibrillation. PMID- 1736580 TI - Predictors of prognosis in severe chronic heart failure. AB - A total of 127 patients with chronic heart failure referred to our exercise laboratory were studied retrospectively to identify parameters predictive of prognosis. Patients were followed for a mean of 14.6 months. The group as a whole had severe ventricular dysfunction with a median ejection fraction of 17% and a median peak rate of oxygen consumption of 13.7 ml/kg/min. During the follow-up period 23 patients (18%) died and 18 (14%) underwent cardiac transplantation. The effect of the following variables on outcome (death or transplantation) were examined: age, cause of heart failure, cardiothoracic ratio on chest radiography, left ventricular end-systolic dimension on echocardiography, left ventricular ejection fraction on radionuclide ventriculography, mean dose of diuretic, plasma sodium and urea concentrations, and peak oxygen consumption during exercise. Although all variables except cause of heart failure affected outcome on univariate analysis, multivariate analysis identified three variables that were statistically significant and independent predictors of outcome. In order of importance these were plasma sodium level, left ventricular ejection fraction and peak oxygen consumption. Even in this group of patients with severe heart failure, these variables were predictive of outcome. PMID- 1736581 TI - Lung and myocardial thallium-201 kinetics in resting patients with congestive heart failure: correlation with pulmonary capillary wedge pressure. AB - Increased lung thallium-201 activity occurs with exercise in patients with severe coronary artery disease as a result of increased pulmonary capillary wedge pressure. No study has shown resting lung kinetics in chronic congestive heart failure. To better understand the relationship between lung and myocardial thallium uptake and pulmonary capillary wedge pressure, this study was performed. Resting lung and myocardial thallium uptake, expressed as a ratio, were compared with simultaneous pulmonary capillary wedge pressure in 16 patients with congestive heart failure and cardiomyopathy, all New York Heart Association class IV. There were no variations in pulmonary capillary wedge pressure throughout the study protocol. There was a significant reduction in the lung/myocardium thallium ratio from 10 to 60 minutes (0.83 +/- 0.30 to 0.59 +/- 0.17; p less than 0.001). At 60 minutes after thallium injection there was a linear correlation between the lung/myocardium ratio and capillary wedge pressure with an r value of 0.62 (p less than 0.01). Thus thallium-201 washout is rapid despite persistence of pulmonary capillary wedge pressure elevation, indicating that clearance does not imply resolution of congestive heart failure. In addition, a significant but imprecise correlation was found between capillary pressure and the lung/myocardium ratio. Rapid changes in lung activity during the early postinjection period may limit the clinical use of the lung/myocardium ratio. PMID- 1736582 TI - Therapeutic effect of oral dipyridamole on myocardial perfusion and cardiac performance in patients with hypertrophic cardiomyopathy. AB - Recent studies have indicated that myocardial ischemia could occur and could play an important role in the pathophysiology of patients with hypertrophic cardiomyopathy (HCM). We therefore investigated whether or not dipyridamole--a selective coronary vasodilating agent--could favorably modify myocardial perfusion and the clinical manifestations in 20 patients with HCM (19 nonobstructive and one mildly obstructive) with an average age of 50 years. Oral dipyridamole, 150 mg/day for 2 weeks, prevented reversible perfusion defects initially observed in six patients on baseline exercise thallium-201 (201TI) scintigraphy and significantly increased the 201TI clearance (40 +/- 13% to 44 +/ 12%), while one patient developed new reversible perfusion defects. There were significant increases in echocardiographic fractional shortening and treadmill exercise time and reductions in cardiac size and supraventricular arrhythmias with dipyridamole therapy. These observations suggest that coronary vasodilation with dipyridamole may improve myocardial perfusion and cardiac function in patients with HCM. PMID- 1736583 TI - Mechanisms for an abnormal radionuclide left ventricular ejection fraction response to exercise in patients with chronic, severe aortic regurgitation. AB - To clarify the mechanisms for an abnormal radionuclide left ventricular (LV) ejection fraction response to exercise in patients with chronic, severe aortic regurgitation (AR), we studied seven control patients and 21 patients with AR. We used exercise radionuclide angiography and catheterization of the right and left sides of the heart to obtain a calculation of LV chamber elastance. The control and AR groups had similar heart rates, systolic blood pressure responses to exercise, and exercise durations. In both patient groups, LV end-diastolic volume did not change with exercise. In contrast to the decrease in LV end-systolic volume (p less than 0.05) and increase in LV ejection fraction (p less than 0.01) in the control group, LV end-systolic volume in the patients with AR increased, resulting in little change in their LV ejection fraction. By stepwise multiple regression analysis, the radionuclide LV ejection fraction at peak exercise in patients with AR was determined by the LV chamber elastance, LV end-systolic volume, and stroke volume at peak exercise (cumulative r = 0.79, p less than 0.02); the change in radionuclide LV ejection fraction from rest to peak exercise was determined by the corresponding change in systemic vascular resistance, regurgitant index, and LV end-diastolic and end-systolic volumes (cumulative r = 0.88, p less than 0.02). These data demonstrate that in patients with AR, the radionuclide LV ejection fraction at peak exercise is principally determined by the cumulative effects of chronic, severe AR on LV systolic chamber performance, and the change in radionuclide LV ejection fraction from rest to peak exercise is principally established by peripheral vascular responses. PMID- 1736584 TI - Percutaneous mitral valvotomy with the Inoue balloon catheter in children and adults: immediate results and early follow-up. AB - Percutaneous mitral balloon valvotomy (PMV) using the Inoue balloon catheter was attempted in 60 consecutive patients with severe symptomatic mitral stenosis. There were 10 children (mean age 13 years) and 50 adults (mean age 31 years). Forty patients were females and 20 were males; 53 were in sinus rhythm. The procedure was technically successfully performed in 57 (95%) patients. There were no deaths or thromboembolic complications. Balloon valvotomy was done using a 22 to 30 mm diameter catheter with the echo/Doppler guided stepwise mitral dilatation technique. After PMV the mean left atrial pressure decreased from 23.0 +/- 5.0 to 14.0 +/- 4.0 mm Hg (p less than 0.001). The mean mitral valve gradient (MVG) decreased from 15.0 +/- 4.0 to 6.0 +/- 2.0 mm Hg (p less than 0.001). The mitral valve area (Gorlin formula) increased from 0.7 +/- 0.2 to 1.6 +/- 0.4 cm2 (p less than 0.001). The mitral valve area as determined by echocardiography increased from 0.8 +/- 0.1 to 1.9 +/- 0.3 cm2 (p less than 0.001). Mild mitral regurgitation (MR) developed in six patients (11%) and increased by one grade in another five patients (9%). No patient developed severe mitral regurgitation. Mitral valve area at mean follow-up of 4.8 months remained unchanged at 1.9 +/- 0.3 cm2. We conclude that PMV, using the Inoue balloon catheter, is safe and effective in the treatment of severe mitral stenosis in children and adults, without inducing significant mitral regurgitation. PMID- 1736585 TI - Superiority of nonpharmacologic therapy compared to propranolol and placebo in men with mild hypertension: a randomized, prospective trial. AB - We compared the effects of nonpharmacologic therapy, propranolol monotherapy, and placebo on blood pressure, metabolic, exercise, and quality of life variables in a 12-week, randomized, placebo-controlled trial of 79 male patients with hypertension. A significant reduction in diastolic blood pressure was observed with both nondrug therapy (-8.0 +/- 1.08 mm Hg) and propranolol (-9.5 +/- 1.46 mm Hg) compared to placebo (-0.1 +/- 2.01 mm Hg). However, only patients receiving nonpharmacologic therapy showed a reduced body mass index, lower total and low density lipoprotein serum cholesterol levels, and increased exercise tolerance compared to both propranolol and placebo. Patients receiving propranolol felt less anxious and unsure but showed a significant decrement in nocturnal penile tumescence compared to both placebo and nondrug therapy. Patients receiving nondrug therapy felt more energetic and reported improved sexual arousal and greater sexual satisfaction after treatment. Reductions in blood pressure in the nondrug treatment group were related to both weight reduction and improved fitness. We conclude that nondrug therapy is effective in controlling blood pressure in men with mild hypertension and is associated with improvements in weight, lipoprotein levels, and exercise tolerance compared to both propranolol and placebo. Quality of life assessments further support the use of nondrug therapy in this context. PMID- 1736586 TI - Prevention of sudden death in survivors of myocardial infarction: a decision analysis approach. AB - During the first year after myocardial infarction, 5% to 15% of patients die, and the majority of deaths occur suddenly. Highly efficacious therapy, such as the implantable cardioverter-defibrillator, may reduce the chance of sudden death, but broad application is limited by associated risks. Hence, attempts to identify patients at high risk so they can receive therapy are desirable. Subgroups with high or low sudden death risks can be identified based on left ventricular function. Further risk stratification using programmed electrical stimulation and the signal-averaged ECG has been advocated, but the best strategy is unknown. Using a decision analysis model, we compared the 1-year survival rates in survivors of myocardial infarction treated with the implantable cardioverter defibrillator either empirically or based on screening with the signal-averaged ECG and programmed electrical stimulation. The best strategy for selecting patients for therapy depended on the pre-therapy sudden death risk. For patients at low risk, such as those with well-preserved ventricular function, antiarrhythmic therapy selected with screening tests or given empirically increased both the mortality rate resulting from the adverse effects of therapy and the excellent survival rate without therapy. In the moderate-risk population, both empiric and stratified approaches reduced mortality, but stratification substantially limited the number of patients receiving unnecessary therapy. In the high-risk population, empiric treatment achieved the best survival rate, and screening resulted in only a small reduction in the number of patients treated unnecessarily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736587 TI - Novel coronary interventional devices: an update. AB - Interventional cardiologists today are overwhelmed by a hugh array of new high technology investigatory devices at their disposal for the treatment of coronary arterial obstructive disease. These include the various atherectomy and laser devices, developed and introduced into clinical practice with the promise and intent of solving the limitations of conventional balloon angioplasty, namely those of acute closure and restenosis. But as more experience and data are obtained from the application of these devices, it is becoming clear that the latter have generally not been able to accomplish what they were intended to do. Although the immediate success rates have been uniformly high, acute closure has persisted and restenosis remains unabated. Nevertheless, some of these new devices have shown some fairly encouraging results in specific clinical circumstances. The targeted use of these instruments may prove to be a step in the right direction. This article reviews the current state of the art and the potential utility of certain of these devices. PMID- 1736588 TI - Serum albumin, coronary heart disease, and death. AB - To confirm a reported association between elevated serum albumin concentrations and reduced risk of death in middle-aged white men and to determine whether such associations exist for CHD incidence in white men and CHD and death in white women and black men and women, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 9 to 16 years, serum albumin concentrations of 4.5 gm/dl or more were associated with reduced risk of CHD incidence in white men aged 45 to 64 years (RR = 0.51; 95% CL = 0.36, 0.73) and in white women aged 45 to 74 years (RR = 0.70; 95% CL = 0.55, 0.88), independent of baseline risk factors. Independent reductions in risk of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also seen in white men and women. Relative risk of death from all causes at ages 45 to 74 years in the white population was 0.73 (95% CL = 0.62, 0.85) for men and 0.71 (95% CL = 0.59, 0.85) for women. Similar reductions in risk of death from all causes and cardiovascular diseases were seen in black men and women, despite the small numbers. Further studies are needed to confirm these findings for women and black persons and to elucidate mechanisms for the effect of serum albumin. PMID- 1736589 TI - Acute thrombotic coronary occlusion secondary to chest trauma treated with intracoronary thrombolysis. PMID- 1736590 TI - Markedly decreased coronary blood flow in secondary polycythemia. PMID- 1736591 TI - Extreme QT prolongation solely due to reversible myocardial ischemia in single vessel coronary disease. PMID- 1736592 TI - Anomalous left circumflex coronary artery from the right pulmonary artery: first adult case report. PMID- 1736593 TI - Coronary involvement in Cogan's syndrome. PMID- 1736594 TI - Early exercise testing after successful percutaneous transluminal coronary angioplasty: a word of caution. PMID- 1736595 TI - Transesophageal echocardiographic diagnosis of acute aortic dissection complicating cocaine abuse. PMID- 1736596 TI - Subclinical traumatic aortic injury diagnosed by transesophageal echocardiography. PMID- 1736597 TI - Ventricular fibrillation induced by transesophageal atrial pacing in asymptomatic Wolff-Parkinson-White syndrome. PMID- 1736598 TI - Discrepancy between head-up tilt test results utilizing different protocols in the same patient. PMID- 1736599 TI - Percutaneous mitral valvotomy by Inoue catheter in young patients with mitral stenosis. PMID- 1736600 TI - Transesophageal echocardiographic diagnosis of complex false aneurysm with aorto left atrial communication complicating aortic valve and root replacement. PMID- 1736601 TI - Repair of postcatheterization femoral pseudoaneurysms by color flow ultrasound guided compression. PMID- 1736602 TI - Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. AB - Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736603 TI - ST-segment depression during dipyridamole infusion, and its clinical, scintigraphic and hemodynamic correlates. AB - The goal of this study was to determine whether dipyridamole-induced ST-segment depression reflects more severe or extensive myocardial hypoperfusion than the absence of this electrocardiographic finding. The clinical, hemodynamic and scintigraphic correlates of ST-segment depression during intravenous dipyridamole infusion were studied in 204 consecutive patients undergoing dipyridamole stress thallium-201 (Tl-201) imaging for evaluation of coronary artery disease. Of 182 patients with a diagnostic baseline electrocardiogram, 28 (15%) developed ST depression after dipyridamole. Patients with ST depression, compared with those without, were older (64 +/- 1 vs 60 +/- 1 years; p less than 0.03) and had a higher frequency of chest pain (57 vs 23%; p less than 0.001) and a higher heart rate-blood pressure product (12.7 +/- 0.6 vs 11.2 +/- 0.2 x 10(3); p less than 0.008) after dipyridamole. Patients with ST depression were more likely to have Tl-201 redistribution (64 vs 38%; p less than 0.02) and a greater number of redistribution defects (2.3 +/- 0.04 vs 0.9 +/- 0.1, p less than 0.001) than were those without ST depression. By multivariate logistic regression analysis, the most powerful correlate of ST depression was the number of segments having Tl-201 redistribution (p less than 0.001). Other independent correlates were presence of chest pain, heart rate at Tl-201 injection, and age. Thus, the determinants of dipyridamole-induced ST-segment depression include the scintigraphic extent of reversible hypoperfusion, as well as indexes of myocardial oxygen demand. PMID- 1736604 TI - Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy. AB - The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication. PMID- 1736605 TI - Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris. AB - To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina. PMID- 1736606 TI - Platelet function after in vivo and in vitro treatment with thrombolytic agents. AB - Whereas in vitro studies showed that plasmin may induce both inhibition and activation of platelets, in vivo and ex vivo investigations suggested that thrombolytic agents are responsible for platelet stimulation. To gain further information on this topic, ex vivo platelet function was studied in 24 subjects with acute myocardial infarction treated with streptokinase or recombinant tissue type plasminogen activator (rt-PA). Ten patients with acute myocardial infarction who did not receive thrombolytic treatment were also investigated. The data shows that at the end of thrombolytic infusion, the maximal extent of platelet aggregation and adenosine triphosphate release was reduced in treated patients compared with that in untreated ones. In subjects treated with streptokinase, the defect in platelet aggregation derived from both cellular and plasmatic defects. Plasmatic beta-thromboglobulin concentration was significantly reduced after streptokinase, but unchanged after rt-PA. Three days after thrombolytic treatment, platelet aggregation of patients receiving streptokinase or rt-PA was not significantly different from that of untreated subjects. A similar defect in platelet function was obtained in vitro, incubating normal platelet-rich plasma with pharmacologic concentrations of streptokinase. Again, platelet function defect derived from both cellular and plasmatic damages. It cannot be excluded that platelet activation occurs in patients with acute myocardial infarction during the very early phases of thrombolytic treatment. However, it is suggested that a transient defect in platelet function follows both streptokinase and rt-PA infusion. PMID- 1736607 TI - Identification of patients at high risk for recurrence of sustained ventricular tachycardia after healing of acute myocardial infarction. AB - A prognostic index for nonfatal recurrences of ventricular tachycardia (VT) was developed using a retrospective analysis of a group of 206 patients with sustained monomorphic VT or ventricular fibrillation (VF) after healing of acute myocardial infarction. 74 patients (36%) (64 with VT and 10 with VF) had recurrences of sustained monomorphic VT during 3.4 +/- 9 years of follow-up. Three clinical variables were selected and weighted by stepwise logistic discriminant analysis of the study group. They were coded as follows: interval of myocardial infarction to arrhythmia (less than 2 months = 1; 2 to 6 months = 2; greater than 6 months = 3), drug therapy with or without sotalol (with = 1, without = 2), and VT or VF as the presenting arrhythmia (VT = 1, VF = 2). The prognostic index was: 3.41 - (0.56 x interval) - (1.94 x therapy) + (0.86 x arrhythmia). This index was validated prospectively in a test group of 158 consecutive patients with VT or VF after healing of acute myocardial infarction. Patients were allocated into different classes with decreasing prognostic index values associated with increasing risk for recurrences of VT. In the test group, 27 of 158 (17%) patients (22 with VT and 5 with VF) had recurrences of VT (follow up of 2 +/- 2 years). Two risk classes of patients were identified: high risk for recurrences of VT (61%) corresponding to patients with a negative index; and low risk (4%) consisting of those with a positive index. Thus, using O as the cutoff point, the sensitivity, specificity, and positive and negative predictive values were 81, 89, 62 and 96%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736608 TI - Correlation of the complete version of the Selvester QRS scoring system with quantitative anatomic findings for multiple left ventricular myocardial infarcts. AB - The correlation between myocardial infarct size estimated by the complete version of the Selvester QRS scoring system and that documented by pathoanatomic studies has been reported for single anterior, inferior and posterolateral infarcts. Although previous studies described electrocardiographic changes in patients with multiple infarcts, no quantitative documentation of the ability of such changes to estimate the total amount of left ventricular infarction has been reported. This study of 32 patients with anatomically documented multiple infarcts shows a significant correlation between QRS-estimated and anatomically documented sizes (r = 0.44; p = 0.01), which is less than that previously reported for single infarcts in the anterior, inferior and posterolateral locations. Several of the 54 electrocardiographic criteria were never satisfied. Criteria for posterior infarction were seldom present, suggesting "cancellation effect" of coexisting anterior infarction. These results will be the basis for future modification of QRS criteria for estimating myocardial infarct size. PMID- 1736609 TI - Percutaneous transluminal coronary rotary ablation with Rotablator (European experience). AB - This study reports the results from 3 European centers using rotary ablation with Rotablator, a device that is inserted into the coronary artery and removes atheroma by grinding it into millions of tiny fragments. Rotary ablation was performed in 129 patients. Primary success (reduction in percent luminal narrowing greater than 20%, residual stenosis less than 50%, without complications) was achieved by rotary angioplasty alone in 73 patients (57%). An additional 38 patients (29%) had successful adjunctive balloon angioplasty. Thus primary success was achieved in 111 patients (86%) at the end of the procedure. Acute occlusion occurred in 10 patients (7.7%). Recanalization was achieved by balloon angioplasty in 7: urgent bypass grafting was undertaken in 2. Q-wave and non-Q-wave myocardial infarction occurred in 3 and 7 patients, respectively. No deaths occurred. Follow-up angiography was performed in 74 patients (60%). Restenosis, defined as the recurrence of significant luminal narrowing (greater than 50%) occurred in 17 of 37 patients (46%) who underwent rotary ablation alone, and 11 of 37 patients (30%) who had adjunctive balloon angioplasty. The overall angiographic restenosis rate was 37.8%. In conclusion, rotary ablation is technically feasible, and relatively safe in the coronary circulation. The low primary success rate reflects the limited size of the device, which can be introduced through available guiding catheters, and limits the use of rotary ablation as a stand-alone procedure to lesions in small arteries or in distal locations. No reduction in restenosis was seen, but the role of this device combined with balloon angioplasty in larger arteries needs to be further defined. PMID- 1736610 TI - Quantitative angiographic follow-up of the coronary Wallstent in native vessels and bypass grafts (European experience--March 1986 to March 1990). AB - The coronary stent has been investigated as an adjunct to percutaneous transluminal coronary angioplasty to obviate the problems of early occlusion and late restenosis. From March 1986 to March 1990, 265 patients (308 lesions) were implanted with the coronary Wallstent in 6 European centers. For this study, the patients were analyzed according to date of implantation (group 1, March 1986 to January 1988; group 2, February 1988 to March 1990) and vessel type (native arteries versus bypass grafts). Quantitative angiographic follow-up was performed in 82% of the study patients. The early in-hospital occlusion rate in the overall group was 15%. Group 1 patients had a 20% rate in contrast to 12% rate in group 2 (p = not significant [NS]). The early occlusion rate in native vessels and bypass grafts was 19 and 8%, respectively (p = 0.019). Restenosis was determined by 2 criteria (criterion 1, greater than or equal to 0.72 mm loss in minimal luminal diameter from poststent to follow-up; criterion 2, greater than or equal to 50% diameter stenosis at follow-up) within the stent and in the segments immediately proximal and distal to the stent. The restenosis rate with criterion 1 was 43% in the overall group of patients, 35% in group 1 versus 49% in group 2 (p = NS), and 34% in native vessels versus 54% in bypass grafts (p = 0.016). The second criterion was met by 27% of patients in the overall group, 21% in group 1 versus 32% in group 2 (p = NS), and 18% in native vessel versus 39% in bypass grafts (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736611 TI - Effects of the dipyridamole test on left ventricular function in coronary artery disease. AB - The dipyridamole stress test is used with thallium-201 to detect areas of inhomogeneity of blood flow that point to coronary artery disease (CAD). It is unclear whether dipyridamole produces inhomogeneous perfusion only or whether it actually decreases net flow in the obstructed vessels and produces true ischemia. It is also unclear what effect dipyridamole has on global and segmental left ventricular function. Therefore, ejection fraction, segmental wall motion and ventricular volume equivalents were measured before and after dipyridamole in 113 patients and 32 normal subjects. Ejection fraction responded in an abnormal fashion in 98 patients (87%), decreasing from 49 +/- 11% to 43 +/- 13% (p less than 0.0001), whereas it increased in 29 normal subjects (90%) from 57 +/- 6% to 64 +/- 10% (p less than 0.0001). Wall motion worsened distinctly in 75 patients (66%), and pressure/volume ratio deteriorated in 72%. The effect of dipyridamole lasted between 10 and 25 minutes, but was promptly reversed by aminophylline. These findings indicate that dipyridamole generally induces true ischemia in CAD. Furthermore, the degree of dysfunction is related to the angiographically assessed severity of CAD. The shortness of breath (seen in 10% of patients) may be partially explained by the findings, and it seems advisable to give aminophylline to every patient in order to promptly correct left ventricular dysfunction. PMID- 1736612 TI - Improvement in left ventricular systolic function after successful radiofrequency His bundle ablation for drug refractory, chronic atrial fibrillation and recurrent atrial flutter. AB - Incessant supraventricular tachyarrhythmia may lead to a reversible impairment of left ventricular (LV) function. This issue was investigated in 10 patients (aged 64 +/- 13 years) who underwent radiofrequency His bundle ablation for control of drug refractory, chronic atrial fibrillation (n = 9) and recurrent atrial flutter (n = 1). LV function was assessed by 2-dimensional guided M-mode echocardiography within 24 hours (baseline) and 49 +/- 18 days (follow-up) after successful ablation, both during VVI pacing at 70 beats/min. Fractional shortening increased from 28 +/- 9% at baseline to 35 +/- 8% at follow-up (p = 0.006). This increase in fractional shortening was due to a significant reduction of end-systolic diameter from 41 +/- 10 to 36 +/- 10 mm (p = 0.02), whereas there was no appreciable change in end-diastolic diameter (56 +/- 7 to 55 +/- 10 mm; p = 0.5). These changes were substantially greater in patients with baseline impairment of LV function (fractional shortening less than 27%). Fractional shortening increased by 12% (p = 0.14) in patients with normal LV function (n = 5) and by 44% (p = 0.02) in those with impaired LV function at baseline (n = 5). The greater increase in fractional shortening in patients with preexisting LV impairment was due to a more pronounced decline in end-systolic dimensions ( 11.9%; p = 0.08) compared with that of patients with normal LV function at baseline (-9.21%; p = 0.2). End-diastolic diameter showed no significant change in either group (-3.53% [p = 0.8] and -0.58% [p = 0.4]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736613 TI - Frequency of recurrent atrial fibrillation after catheter ablation of overt accessory pathways. AB - The effect of successful catheter ablation of overt accessory pathways on the incidence of atrial fibrillation (AF) was studied in 129 symptomatic patients with (n = 75) or without (n = 54) previous documented AF. Fourteen had had ventricular fibrillation. Factors predictive of recurrence were examined, including electrophysiologic parameters. Atrial vulnerability was defined as induction of sustained AF (greater than 1 minute) using single, then double, atrial extrastimuli at 2 basic pacing cycle lengths. When compared to patients with only reciprocating tachycardia, patients with clinical AF included more men (77 vs 54%, p = 0.008) and were older (35 +/- 12 vs 29 +/- 12 years, p = 0.01). They had a significantly shorter cycle length leading to anterograde accessory pathway block (252 +/- 42 vs 298 +/- 83 ms, p less than 0.001), greater incidences of atrial vulnerability (89 vs 24%, p less than 0.001) and subsequent need for cardioversion (51 vs 15%, p less than 0.001). After discharge, the follow-up period was 35 +/- 12 months (range 18 to 76); 7 patients with previous spontaneous AF (9%) had recurrence at a mean of 10 months after ablation. Age, presence of structural heart disease accessory pathway location, atrial refractory periods and accessory pathway anterograde conduction parameters were not predictive of AF recurrence. Persistence of atrial vulnerability after ablation was the only factor associated with further recurrence of AF. Atrial vulnerability was observed after ablation in only 56% of patients with previous AF versus 89% before ablation. It is concluded that successful catheter ablation of accessory pathways prevents further recurrence of AF in 91% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736614 TI - Efficacy of intravenous sotalol for suppressing inducibility of supraventricular tachycardias at rest and during isometric exercise. AB - The efficacy of intravenous sotalol (1 mg/kg) for suppressing inducibility of supraventricular tachycardias (SVT) with different electrophysiologic mechanisms was studied in 30 consecutive patients referred for an electrophysiologic study because of paroxysmal SVT. Orthodromic SVT using accessory atrioventricular (AV) connection was inducible in 14 patients, AV nodal reentrant SVT in 8, and intraatrial SVT in 8 before administration of sotalol, Isometric handgrip exercise facilitated the inducibility of SVT in 8 patients who were noninducible at rest. After intravenous sotalol, 7 of 14 patients (50%) with orthodromic SVT, 8 of 8 (100%) with AV nodal reentrant SVT, and 8 of 8 (100%) with intraatrial reentrant SVT became noninducible into sustained SVT, Isometric exercise facilitated the inducibility of only 3 nonsustained SVT runs after sotalol infusion, and exercise did not reverse the prolongation of refractory periods of the atrium, AV node, accessory pathway and ventricle caused by sotalol. During a mean follow-up period of 18 +/- 7 months, none of the 14 patients who remained noninducible into sustained SVT during the stress test after intravenous sotalol and tolerated long-term oral sotalol therapy had recurrence of symptomatic SVT. Thus, sotalol is efficacious for suppressing SVT with AV nodal or intraatrial reentrant mechanism, but less efficacious in patients with accessory AV pathway. The beta-blocking and cellular antiarrhythmic effects of sotalol are not significantly reversed by exercise. PMID- 1736615 TI - Conversion of typical to "atypical" atrioventricular nodal reentrant tachycardia after radiofrequency catheter modification of the atrioventricular junction. AB - Typical atrioventricular (AV) nodal reentry tachycardia (AVNRT) is characterized by anterograde activation over a slowly conducting pathway and by retrograde activation through a rapidly conducting pathway. Preliminary reports suggest that radiofrequency catheter modification can eliminate typical AVNRT while preserving anterograde conduction. Radiofrequency catheter modification was used to treat 88 patients with typical AVNRT. After baseline electrophysiologic evaluation, the ablation catheter was positioned proximal and superior to the site of maximal His deflection. Radiofrequency energy was applied until there was significant attenuation of retrograde conduction, and elimination of AVNRT inducibility. Eighty-one patients were successfully treated and form the basis of this report. A new paroxysmal supraventricular tachycardia with RP greater than PR interval was induced at electrophysiologic testing after successful ablation in 9 patients (11%). Mean atrial-His activation time was 140 +/- 31 ms, and the ventriculoatrial activation time was 170 +/- 46 ms. This arrhythmia was induced only with ventricular pacing during isoproterenol infusion and appeared to be mediated by AV nodal reentry. New retrograde dual AV nodal physiology after modification was more frequent in patients with atypical tachycardia than in those without (4 of 9 vs 2 of 72; p less than 0.0001). Although none of the patients were treated, only 1 of 9 had an episode of spontaneous atypical tachycardia during a mean follow-up of 12 months. Results of this study confirm that typical AVNRT can be rendered noninducible without the complete destruction of reentrant pathways. Because induction of "atypical" AVNRT was not predictive of spontaneous arrhythmia recurrence, it should not be an indication for additional ablation sessions or long-term drug therapy. PMID- 1736616 TI - Effect of epinephrine on the efficacy of the internal cardioverter-defibrillator. AB - To evaluate the effect of sympathetic activation on the efficacy of the implantable cardioverter-defibrillator (ICD) in converting ventricular tachycardia (VT) or ventricular fibrillation (VF), 32 patients who received an ICD because of life-threatening VT/VF underwent 1 week postimplant ICD testing both before and after infusion of 25 (16 patients) or 50 (16 patients) ng/kg/min of epinephrine for greater than or equal to 12 minutes. These infusion rates are known to result in plasma epinephrine concentrations comparable to mild-moderate stress. The patients' mean age was 63 +/- 10 years; 26 had coronary artery disease, 2 had dilated cardiomyopathy and 4 had no evidence of structural heart disease. VT and VF were induced in 16 patients each by programmed stimulation or alternating current. Among the 16 patients with VT, the first ICD discharge (26 to 30 J) was effective in 15 patients in the baseline state and in all 16 patients during epinephrine infusion. Among patients with VF, the first ICD discharge (26 to 30 J) terminated VF in all patients in the baseline state, compared with 12 of 16 patients during epinephrine infusion (p less than 0.05). In 4 patients, VF was terminated during epinephrine infusion only by the second or third ICD discharge (30 J). In conclusion, physiologic increases in the plasma epinephrine concentration may increase the number and energy of shocks needed to terminate VF. PMID- 1736617 TI - Clinical and electrophysiologic effects of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with angina pectoris. AB - Dofetilide (UK-68,798) is a new class III antiarrhythmic agent. In animal experiments it selectively prolongs the refractory periods parallel to the action potential duration without any influence on upstroke velocity or conduction parameters. The present double-blind, placebo-controlled study was designed to show the effect of dofetilide on basic electrophysiologic parameters in patients with coronary artery disease. Eighteen patients (aged 31 to 64 years) with symptoms of stable angina pectoris admitted for routine coronary angiography were recruited. They were randomly allocated to receive either placebo or 1 of 2 dose levels of dofetilide intravenously with 6 patients in each group. Paired electrophysiologic variables were compared before and after administration of dofetilide. Both active dose levels produced significant prolongations (p less than 0.05) of 10 to 23% in atrial effective refractory period, 6 to 16% in ventricular effective refractory period and 11 to 15% in ventricular functional refractory period. Atrial functional refractory period was prolonged by 14 to 22% at the high-dose level (p less than 0.05). No effect was observed on conduction parameters (PA, AH, HV, PR or QRS intervals), sinus cycle length or sinus node recovery. The selective prolongation of the refractory periods in both atrium and ventricle, combined with a lack of effect on cardiac conduction parameters, indicates that this drug could be useful in the treatment of both atrial and ventricular reentrant tachyarrhythmias and fibrillation. PMID- 1736618 TI - Effects of heart failure on baroreflex control of sympathetic neural activity. AB - Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1736619 TI - Effect of captopril on cardiac parasympathetic activity in chronic cardiac failure secondary to coronary artery disease. AB - Thirty-two patients with chronic cardiac failure underwent 24-hour ambulatory electrocardiographic monitoring on 2 separate occasions: 20 patients before and during treatment with captopril, and 12 acting as controls. Heart rate variability was calculated by counting the number of times successive RR interval differences were greater than 50 ms (this measurement being a reliable index of cardiac parasympathetic activity). During treatment with captopril, group mean total counts increased to 1,032 (range 48 to 7,437) from 482 (range 23 to 6,120) (p = 0.002). There was no change in mean hourly waking or sleeping heart rates. In the control group, no changes were seen: group mean total counts on the first occasion were 340 (range 120 to 3,255) and on the second occasion 400 (range 154 to 3,300) (p = not significant). These results show that treatment with angiotensin-converting enzyme inhibitors increases cardiac parasympathetic activity in patients with chronic cardiac failure. This may be relevant to the improved prognosis of this group of patients when treated with angiotensin converting enzyme inhibitors. PMID- 1736620 TI - Late (two-year) follow-up after percutaneous balloon mitral valvotomy. AB - Percutaneous balloon mitral valvotomy (PBMV) compares well with surgical commissurotomy, showing comparable improvement in symptoms and catheterization proven valve area early after the procedure. This study reports the New York Heart Association class, mitral valve area calculated by echocardiography, and the results of transseptal cardiac catheterization 2 years after PBMV. The data are compared with the status immediately before and after PBMV. Forty-one patients returned to enter the study (mean follow-up time 24 +/- 3 months). All patients were evaluated clinically by the same investigator who had seen them at the time of PBMV. Transseptal cardiac catheterization and echocardiographic analysis (2-dimensional and Doppler echocardiography) were performed on the same day. At follow-up, 17 patients were class I, 20 were class II, and 4 were class III. Although the mitral valve area calculated by cardiac catheterization increased significantly from immediately before to immediately after PBMV there was a decrease in the calculated mitral valve area at 2-year follow-up. Echocardiographic analysis did not show as large an increase in mitral area, immediately after PBMV, and no significant decrease in mitral valve area at 2 years (before PBMV planimetry 1.1 +/- 0.1 cm2; immediately after 1.8 +/- 0.1 [p less than 0.05]; follow-up 1.6 +/- 0.1 [p = not significant compared with immediately after PBMV]). Doppler halftime measurements were similar. PBMV is effective therapy with good midterm results for selected patients with mitral stenosis. PMID- 1736621 TI - Reproducibility of quantitative backscatter echocardiographic imaging in normal subjects. AB - Cyclic backscatter variation is useful in differentiating normal from ischemic and myopathic myocardium; however, there are few data on the reproducibility of clinical cyclic variation measurements. Therefore, a study using 2-dimensional and M-mode backscatter imaging was performed in 20 normal male subjects by 2 observers at an initial session and by 1 of the observers after 1 week. Cyclic variation on M-mode was calculated as the difference between the end-diastolic backscatter and the backscatter at the nadir. Two-dimensional determinations of backscatter were made using a single frame at end-diastole and one at end systole. The cyclic change was the difference between backscatter measured in the end-diastolic and end-systolic frames. There were no statistically significant differences in analysis of variance among the grouped repeated measurements in either the interventricular septum or the posterior left ventricular wall. At the initial session, cyclic backscatter variation in the posterior wall using M-mode techniques was 5.9 +/- 1.8 dB (SD). The cyclic change in backscatter in the septal wall, using the 2-dimensional technique, was 4.3 +/- 2.4 dB. In the posterior wall, the cyclic change in backscatter was 5.7 +/- 1.7 dB. Pairwise observer correlations between repeated measurements ranged from -0.48 to 0.45. Thus, although there were no significant differences in group means on repeat measurements, repeated measurements in individual subjects were not reliably reproduced because of limited independent sampling of backscatter measurements at only 2 points in the heart cycle. Increased independent sampling and measurement from a backscatter waveform throughout the cardiac cycle may improve reproducibility of measurements. PMID- 1736622 TI - Effects of cardiac transplantation on ventilatory response to exercise. AB - Patients with heart failure frequently exhibit an excessive ventilatory response to exercise, which is acutely unaltered by therapeutic interventions. To investigate whether these ventilatory responses resolve after cardiac transplantation, 15 ambulatory patients with severe heart failure underwent exercise testing with measurement of respiratory gases before and 1.4 +/- 0.6 years [corrected] after transplantation. Ventilatory response was also measured in 7 age-matched, sedentary control subjects. Left ventricular ejection fraction at rest and hemodynamic measurements were obtained before and after transplantation in all patients. After transplantation, ejection fraction at rest increased from 16 +/- 6 to 56 +/- 10%, pulmonary capillary wedge pressure declined from 26 +/- 8 to 12 +/- 5 mm Hg, and cardiac index increased from 1.7 +/ 0.5 to 2.8 +/- 0.5 liters/min/m2 (all p less than 0.001). Peak oxygen consumption increased from 11.8 +/- 1.9 to 19.2 +/- 3.1 ml/kg/min (p less than 0.001), but remained significantly lower than that in control subjects (33.4 +/- 6.9 ml/kg/min; p less than 0.01). Minute ventilation (VE) was significantly reduced after transplantation, but excessive compared with normal values. Ventilation at a carbon dioxide production of 1 liter/min decreased significantly after cardiac transplantation (52.1 +/- 7.9 to 38.8 +/- 3.8 liters; p less than 0.01), but remained elevated when contrasted to that in control subjects (31.4 +/ 3.4 liters; p less than 0.05). Ventilatory response to exercise is significantly improved after cardiac transplantation; however, VE remains excessive. This may reflect an attenuated cardiac output response to exercise, abnormal intrapulmonary pressures or persistent deconditioning. PMID- 1736623 TI - Influence of residual blood flow in the infarct-related artery on ventricular tachycardia after myocardial infarction. PMID- 1736624 TI - Prevalence of silent myocardial ischemia detected by 24-hour ambulatory electrocardiography, and its association with new coronary events at 40-month follow-up in elderly diabetic and nondiabetic patients with coronary artery disease. PMID- 1736625 TI - Detection of patent foramen ovale by transcranial contrast Doppler ultrasound. PMID- 1736626 TI - Estimation of pulmonary arterial wedge pressure by pulsed Doppler echocardiography and phonocardiography. PMID- 1736627 TI - Richard Lower (1631-1691): a pioneer of cardiologic research. PMID- 1736628 TI - Assessment by echocardiogram of left ventricular diastolic function in healthy subjects using the atrioventricular plane displacement. PMID- 1736629 TI - Cytologic analysis of pericardial effusion complicating extracardiac malignancy. PMID- 1736630 TI - Thallium stress tests in asymptomatic diabetics. PMID- 1736631 TI - Seismocardiography is not a new term. PMID- 1736632 TI - Single Inoue balloon catheter versus double Mansfield balloon catheter techniques in percutaneous balloon mitral valvuloplasty. PMID- 1736634 TI - Importance of family history in adolescent gallbladder disease. PMID- 1736633 TI - Clinical features of vascular thrombosis following varicella. AB - OBJECTIVE: To define the clinical characteristics, neuroimaging features, and outcome of five patients with post-primary varicella zoster virus infection hemiparesis and to offer a hypothesis to explain the predilection for the involvement of the cerebral vasculature in this condition. DESIGN: Patient series. SETTING: Five patients were treated during a 14-month period in a private pediatric neurology practice in a medium-size southwestern city. INTERVENTIONS: Steroids (two patients) and antiplatelet drugs (two patients). No observed effects of therapy. RESULTS: The onset of the hemiparesis occurred several weeks (mean, 5.4 weeks) following an episode of the chickenpox. Magnetic resonance imaging was more sensitive than computed tomography or angiography in demonstrating the area of involvement deep in the cerebral hemispheres. The prognosis was good regardless of the therapy administered, as all patients recovered completely or nearly completely. CONCLUSIONS: Primary varicella zoster virus infection with delayed-onset hemiparesis typically occurs approximately 6 weeks after primary varicella zoster virus infection. Magnetic resonance imaging is the most sensitive neuroimaging tool in these children. The prognosis is good, with recovery of function and no recurrences in our patients. The innervation of the carotid artery and the characteristics of the varicella zoster virus itself together provide the local and systemic factors that may trigger the vasculopathy responsible for this syndrome. PMID- 1736635 TI - Pathological case of the month. Wilson's disease (hepatolenticular degeneration). PMID- 1736636 TI - Radiological case of the month. Absent pulmonic valve presenting with congenital lobar emphysema. PMID- 1736637 TI - Picture of the month. Congenital syphilis. PMID- 1736638 TI - God, gays, and health care provision. PMID- 1736639 TI - Tetralogy of Fallot. The spectrum of severity in a regional study, 1981-1985. AB - The combined medical and surgical mortality rate for 125 infants with tetralogy of Fallot registered in the Baltimore-Washington Infant Study from 1981 to 1985 was 28% (mean age at follow-up for living infants, 40 months). Despite early diagnosis and successful early repair in many infants, significant risk factors for death included pulmonary atresia, major additional cardiac anomalies, major noncardiac malformations, low birth weight, and prematurity. There is a wide spectrum of severity, ranging from infants with isolated tetralogy and no risk factors who have an excellent prognosis to infants with three or more risk factors and a high probability of neonatal death. Further treatment advances will improve outcome in some, but not all, infants. A regional all-inclusive study of a specific cardiac defect can define research and treatment challenges not obvious from selected clinical series. PMID- 1736640 TI - Breath-holding spells in childhood. AB - Childhood breath-holding spells are a common and frightening phenomenon occurring in healthy, otherwise normal children. They have been well recognized for several hundred years. There appear to be two clinical forms: the cyanotic type and the pallid type, referring to the color change exhibited by the child during the episode. Prior research concerning the underlying pathophysiologic mechanisms involved in breath-holding spells has implicated an autonomic nervous system dysregulation. Cerebral anoxia is the ultimate factor responsible for the loss of consciousness observed in the severe forms of breath-holding spells. The clinical and epidemiologic aspects of breath-holding spells are herein summarized. The pertinent respiratory and neural physiologic interactions involved are delineated, as well as practical treatment approaches. PMID- 1736641 TI - The problem of indigent children: shutting off the supply. PMID- 1736642 TI - Is there a 'gold standard' for drug detection in pregnancy? PMID- 1736644 TI - Bones of today, bones of tomorrow. PMID- 1736643 TI - Autologous transfusions for neonates using placental blood. A cautionary note. PMID- 1736645 TI - Bone mineral density in 15- to 21-year-old eumenorrheic and amenorrheic subjects. AB - The purposes of this study were to compare the lumbar spine bone mineral density of eumenorrheic and amenorrheic white subjects aged 15 to 21 years, and to describe the femoral neck bone mineral density in the eumenorrheic subjects. Twenty-eight eumenorrheic females had lumbar bone mineral density (mean +/- SD) of 1.213 +/- 0.117 g/cm2, and femoral neck bone mineral density of 1.032 +/- 0.092 g/cm2 measured with dual energy x-ray absorptiometry. Bone mineral density at neither site was related to age, energy intake, or calcium intake. Femoral neck bone mineral density was related to energy expenditure. Body composition was measured with total body electrical conductivity, and bone mineral density at both sites was related to body weight as much as fat-free mass. Eight amenorrheic subjects had a lumbar spine bone mineral density of 1.057 +/- 0.113 g/cm2, which was lower than in the eumenorrheic group. However, when controlling for weight, this difference was not significant. Peak lumbar and femoral neck bone mineral density may be reached at midadolescence. PMID- 1736646 TI - Retrieval of placental blood from the umbilical vein to determine volume, sterility, and presence of clot formation. AB - From August 1988 to October 1989, 60 specimens of citrate-phosphate-dextrose adenine anticoagulated blood were retrieved from the placental umbilical veins of newborns from three gestational age groups. The specimens were removed with a needle and syringe apparatus and placed directly into sterile transfusion packs. The specimens were evaluated for the volume obtained, sterility, and presence of macroscopic clots. A blood volume sufficient to provide at least one transfusion (10 mL/kg) for 87% of the premature infants studied was retrieved from the placenta. A greater blood volume per unit of birth weight was recovered from the placentas of the smaller newborns. A 12% positive culture frequency and a 7% frequency of detectable clots were identified. These rates of occurrence suggest the need for further studies to determine the origins of these complicating factors before the adoption of this technique in the clinical setting. These findings support the hypothesis that, with proper patient selection and with specimen culture and filtration, placental blood may be a viable option for the autologous transfusion of sick, premature infants. PMID- 1736647 TI - Very low birth weight and growth to age 8 years. I: Weight and height. AB - We determined the heights and weights at ages 2, 5, and 8 years for the following three cohorts of children: group 1 with birth weights between 500 and 999 g; group 2 with birth weights between 1000 and 1499 g; and group 3 with birth weights more than 2500 g. By age 8 years, group 3 children were significantly heavier and taller than all children in groups 1 and 2 combined; group 1 children were significantly shorter than those in group 2, but their weights were similar. From ages 2 to 5 years, annual increments in weight and height were similar in all three groups; however, between ages 5 and 8 years, children in group 3 grew faster than those in groups 1 and 2 combined, and children in group 1 had smaller height increments than those in group 2. Of children with birth weights less than 1500 g, with a weight or height under the 10th percentile at age 2 years, only approximately one half were still below the 10th percentile for the corresponding measurement at age 8 years. Health variables determined before birth, such as maternal height or birth weight ratio, were more important than health after birth in predicting a height or weight below the 10th percentile at age 8 years in children with birth weights less than 1500 g. PMID- 1736648 TI - Very low birth weight and growth to age 8 years. II: Head dimensions and intelligence. AB - The occipitofrontal circumference was measured in all available children in the following cohorts at ages 2, 5, and 8 years: group 1, consisting of 79 children with birth weight between 500 and 999 g; group 2, with 111 children with birth weight between 1000 and 1499 g; and group 3 with 56 children with birth weight greater than 2500 g; all were white with no signs of moderate or severe cerebral palsy. National Center for Health Statistics reference values indicated substantially more children with an occipitofrontal circumference lower than the 10th percentile, particularly at age 2 years, compared with Nellhaus reference data. Occipitofrontal circumference was the head measurement best correlated with the Full Scale IQ on the Wechsler Intelligence Scale for Children-Revised. Dolichocephaly, often seen in very-low-birth-weight children was unrelated to IQ, and correction of occipitofrontal circumference for dolichocephaly was rarely of clinical importance. PMID- 1736649 TI - Multiple realities. Teaching rounds in an inpatient pediatric service. AB - Teaching rounds are a mainstay of most educational programs for interns and residents, but little is known about how they are conducted and the role they play in house staff members' learning. We performed a qualitative study of teaching rounds in an inpatient adolescent service using five data sources: observations, interviews, house staff ratings, results of a house staff retreat, and documents outlining faculty responsibilities. Interns, senior residents, and faculty members expressed differing views regarding the purpose, process, and content of rounds; mutual roles and expectations; and time management. An interactive teaching format focused around the visit of a patient to the conference room stimulated house staff interest and learning to a greater extent than did more traditional case presentations and lectures. These results suggest a need to develop a consensus among faculty and house staff regarding the purpose, content, and process of rounds. PMID- 1736650 TI - Body size and composition of perimenarchal girls. AB - A number of measurements are reported on a cross-sectional sample of girls who were studied at times ranging from 54 months prior to menarche to 82 months after menarche. Included are anthropometric measurements, lean weight, body fat, abdomen-hip ratio, skeletal size, bone age, muscle strength, and urinary hydroxyproline excretion. The years preceding menarche are associated with an array of physiological and anatomical changes, making it difficult to assign a causative role to any one of them. PMID- 1736651 TI - Indications of early obesity in low-income Hmong children. AB - OBJECTIVE: To determine if there is evidence of obesity in low-income Hmong children. DESIGN: Cross-sectional survey. SETTING: Women, Infants, and Children clinics in Minneapolis, Minn. PARTICIPANTS: 271 US-born Hmong children, ages 1.00 through 4.99 years. SELECTION PROCEDURES: Consecutive sample of all Hmong children seen in two clinics between September and December 1989. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Heights and weights were measured and converted to National Center for Health Statistics z scores of weight for age, height for age, and weight for height. Relative to National Center for Health Statistics reference data, mean height-for-age z scores decline progressively after age 2 years to--1.2 z at age 4.5 years. Mean weight-for-height z scores exceeded the National Center for Health Statistics reference significantly at ages 3 and 4 years, and there was more than a fourfold excess of Hmong children beyond the 95th percentile in weight for height at these ages. CONCLUSIONS: There is evidence of early obesity in Hmong children, an ethnic group heretofore considered to be a low risk for obesity. PMID- 1736652 TI - Findings from the preparticipation athletic examination and athletic injuries. AB - This study investigated the relationships between the findings from a standardized preparticipation athletic examination, the sport played, and athletic injuries requiring treatment by a physician and/or requiring the athlete to miss one or more games. Of public high school students receiving a preparticipation athletic examination during the 1989-1990 academic year, 674 (56%) either completed a telephone interview or returned a mailed questionnaire at the end of the academic year. The sample consisted of 408 (60.5%) blacks and 243 (36.1%) whites; 470 (69.7%) of the subjects were males. The subjects ranged in age from 13 to 20 years (mean +/- SD, 16.1 +/- 1.2 years), and participated in at least 10 school sports. Injuries were reported by 29.5% of the athletes. The highest proportion of athletes injured occurred among male football (36.3%), female basketball (33.3%), male baseball (19.4%), male soccer (17.2%), and female track and field (15.8%) participants. Responses by the athletes and their parents on the standardized health history were significantly associated with injuries in several specific areas. Knee injuries were associated with previous knee injuries, knee surgery, and history of injuries requiring medical treatment. Ankle injuries were associated with previous ankle injuries and previous injuries requiring medical treatment. Both arm and other leg injuries were associated with previous fractures. Male athletes with either abnormal knee or ankle findings from the physical examination were more likely to injure the knee or ankle, respectively. However, the sensitivities and positive predictive values of these relationships are weak. These data suggest that the preparticipation athletic examination may not predict certain athletic injuries and that additional prevention efforts for specific body areas of injury are needed in certain sports. PMID- 1736653 TI - Severe insulin resistance and diabetes mellitus in mandibuloacral dysplasia. AB - Mandibuloacral dysplasia (MAD) is a syndrome with onset in midchildhood. The predominant characteristics of MAD include flexion contractures; mandibular hypoplasia; loss of body fat; atrophic, speckled skin; and progressive osteolysis of the clavicles. We studied three males with MAD. Each had lipodystrophy of the extremities, with sparing of the face and neck. All had moderate hyperlipidemia. In response to oral glucose, each had a diabetic response, with peak insulin levels between 2870 and 22,960 pmol/L. Insulin-stimulated glucose disposal was determined in two patients with MAD. At an insulin infusion rate of 120 mU/m2 per minute, glucose disposal was less than 25% of that measured at similar levels of insulinemia in nondiabetic control subjects, indicating marked insulin resistance in patients with MAD. The insulin resistance occurred without obesity, excessive levels of counterregulatory hormones, or anti-insulin-receptor antibodies. We suggest that MAD is a previously undescribed form of lipodystrophic insulin resistant diabetes mellitus. PMID- 1736654 TI - Re: Maternal smoking and tubal pregnancy. PMID- 1736655 TI - Re: "The effect on the stratum-specific odds ratios of nondifferential misclassification of a dichotomous covariate". PMID- 1736656 TI - Particulate air pollution and daily mortality in Steubenville, Ohio. AB - Particulate air pollution has been associated with daily mortality in London, England, both in the smog episodes of the 1950s and at the lower pollution levels of the late 1960s and early 1970s. Replicating these findings in the United States has been difficult, because particulates are usually sampled every sixth day. Replication, particularly with a gravimetric measure of particulates, is important in assessing the causality of the relation. Daily measurements of total suspended particulates by high volume gravimetric sampler are available for the Steubenville, Ohio, metropolitan area. These were matched to daily mortality counts from the detail mortality tapes of the National Center for Health Statistics. Deaths of residents which occurred outside the Steubenville Standard Metropolitan Statistical Area were excluded. Because of the much smaller population, the average total number of deaths per day in the Steubenville Standard Metropolitan Statistical Area over the 11-year period 1974-1984 was about 1% of the deaths in a typical London winter. Despite this reduced statistical power, total suspended particulate count was significantly associated with increased daily mortality in Poisson regression analyses controlling for season and temperature. An increase in particulates of 100 micrograms/m3 was associated with a 4% increase in mortality on the succeeding day. Associations with sulfur dioxide were not significant after adjustment for particulates. The relation appeared to continue at levels well below the current National Ambient Air Quality Standard. PMID- 1736657 TI - Association of smoking and alcohol drinking with residential fire injuries. AB - To investigate whether tobacco, alcohol, and their combined use are important risk factors for fire injuries, the authors analyzed data from a population-based case-control study in King County, Washington, between 1986 and 1987. Cases (n = 116) were households with at least one fatal or nonfatal unintentional residential fire injury reported to the Washington State Fire Incident Reporting System from 1984 through 1985. Controls were selected by random digit dialing (n = 256). After adjustment for household size, number of male household members, total household income, and education of the head of the household, the odds ratio for fire injury in households whose members collectively smoked 1-9 cigarettes per day was 1.5 (95% confidence interval (CI) 0.6-4.2) relative to households with no smokers; for 10-19 cigarettes per day, the odds ratio was 6.6 (95% CI 2.5-17.5), and for 20 or more cigarettes per day, it was 3.6 (95% CI 1.9 7.2). Although households with alcohol drinkers who consumed five or more drinks per occasion were found to be at increased risk in the crude analysis, multivariate analysis suggested that this was partly because drinkers tended to live in households with higher smoking levels. Thus, even though households with alcohol drinkers who consume five or more drinks per occasion may be at increased risk of residential fire injury, smoking appears to be the more important underlying risk factor. PMID- 1736658 TI - Family history of reproductive cancers and ovarian cancer risk: an Italian case control study. AB - The relation between family history of ovarian, breast, and endometrial cancer and risk of epithelial ovarian carcinoma was analyzed within the framework of a case-control study conducted from 1983 to 1989. The study included 755 cases of ovarian cancer and 2,023 controls in hospital for a spectrum of acute nongynecologic, hormonal, or neoplastic conditions in the Greater Milan area, Italy. Eighteen cases (2%) and 24 controls (1%) reported a history of ovarian cancer in a first-degree relative: The corresponding multivariate adjusted odds ratio (OR) was 1.9 (95% confidence interval (CI) 1.1-3.6). The risk of ovarian cancer was elevated in women reporting a family history of breast cancer (OR = 1.6, 95% CI 1.1-2.3), but no significant association emerged with a family history of endometrial cancer (OR = 1.3, 95% CI 0.8-1.7). When the data were stratified by family history of breast cancer, a family history of ovarian cancer was over 10 times more frequent in both cases and controls who reported a family history of breast cancer than in cases and controls reporting no family history of breast cancer. The estimated odds ratio for ovarian cancer associated with a family history of the disease was 2.3 (95% CI 1.1-4.5) in women not reporting a family history of breast cancer, but no association emerged in the subgroup of women reporting a family history of breast cancer. These results confirm that a family history of ovarian cancer increases the risk of the disease, but the percentage of ovarian cancer cases explained by a family history of the disease is small: Less than 1% of observed cases in this study could be attributed to this "family risk factor." PMID- 1736659 TI - Chlamydia trachomatis infection in women: a need for universal screening in high prevalence populations? AB - Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen. Nevertheless, selective, rather than universal, screening for chlamydia has been recommended, largely because testing is expensive and requires considerable technical expertise. A total of 1,348 women in four family planning clinics in San Francisco, California, were screened from March 1987 to January 1988 to identify criteria for selective screening. Of these, 9.2% had a positive chlamydia test using direct fluorescence. Logistic regression analysis identified five factors associated with infection: age less than 25 years, cervical friability, single marital status, a new sexual partner within the past 3 months, and lack of barrier contraceptive use. No single risk factor or combination of risk factors had both a high sensitivity and a high positive predictive value for infection. While screening all women who were unmarried would detect 93% of those with chlamydia, the positive predictive value of 10.7% was not much higher than the overall prevalence. Conversely, screening all women with cervical friability, which had a positive predictive value of 23.2%, would only detect 11% of those with chlamydia. On the basis of the authors' findings, selective screening should not be used in high prevalence populations in which all women are at risk and should be screened for chlamydia. PMID- 1736660 TI - Aspergillus fumigatus sternal wound infections in patients undergoing open heart surgery. AB - During a 21-month period (July 1986-April 1988), six patients who underwent open heart surgery at Holston Valley Hospital and Medical Center in Kingsport, Tennessee, developed sternal would infections caused by Aspergillus fumigatus. All patients required sternectomy, reconstructive surgery, and long term amphotericin B therapy; no patient died. By univariate analysis, the following were significantly associated with A. fumigatus sternal would infection: chronic lung disease, a recent history of pneumonia, a greater mean number of admission diagnoses, and a particular surgeon. However, multivariate analysis identified chronic lung disease as the only independent risk factor and the best predictor of A. fumigatus sternal wound infections. No factors related to the surgical procedure or operating room personnel were associated with infection. A review of the characteristics of the patients undergoing open heart surgery showed that since 1985, there had been a trend for these patients at Holston Valley Hospital and Medical Center to be older and sicker, which may have contributed to the occurrence of infections never observed before. Despite an extensive investigation, no environmental source for A. fumigatus was identified. A. fumigatus, however, grew from the bronchial washing of one patient at the time the sternal wound infection was diagnosed, and a prospective study showed that the rate of A. fumigatus colonization among open heart surgery patients was the same as the rate of sternal wound infections caused by A. fumigatus. These data suggest that patients with chronic lung disease and respiratory colonization with A. fumigatus are at increased risk for A. fumigatus sternal wound infections after open heart surgery. PMID- 1736661 TI - Socioeconomic status, John Henryism, and blood pressure in black adults. The Pitt County Study. AB - The joint influence of socioeconomic status and John Henryism on blood pressure was examined in a probability sample of 1,784 black adults aged 25-50 years in Pitt County, North Carolina, in 1988. John Henryism was measured by means of the John Henryism Active Coping Scale. Socioeconomic status (low, medium, and high) was based on respondents' education and occupation. Prior research indicated that, for blacks, the inverse association between socioeconomic status and hypertension may be stronger for individuals who score high in John Henryism. In this more urban sample of blacks, the hypothesized interaction achieved modest statistical support (p less than 0.08) only for hypertension prevalence. For individuals with high levels of John Henryism, adjusted prevalences declined with increasing socioeconomic status (29.4%, 26.2%, and 20.5% for low, medium, and high socioeconomic status, respectively); for individuals with low levels of John Henryism, hypertension prevalence was similar in the low (22.6%) and medium (22.8%) socioeconomic categories but higher in the high socioeconomic category (25.9%). Elevated psychological stress in white-collar workers was probably responsible for the nonsignificant inverse gradients between socioeconomic status and mean blood pressures and for the weak interaction between socioeconomic status and John Henryism with regard to hypertension prevalence. PMID- 1736662 TI - Cross-sectional and longitudinal associations between high density lipoprotein cholesterol and women's employment. AB - This study examined the association between women's employment and high density lipoprotein (HDL) cholesterol. Subjects were 1.998 women aged 25-64 years who were sampled by the first MONICA Augsburg Survey (Monitoring of Trends and Determinants in Cardiovascular Disease). The women were sampled from the population of Augsburg, Federal Republic of Germany, in 1984-1985, were followed up for 3 years, and were reexamined in 1987-1988. In cross-sectional analysis (1984-1985), the mean HDL cholesterol level of employed women was 3.4 mg/dl higher than that of full-time homemakers (p less than 0.001). After adjustment for age, body mass, cigarette smoking, consumption of coffee and alcohol, use of sex hormones, leisure-time physical activity, and reproductive history, this difference decreased to 2.1 mg/dl and remained statistically significant (p less than 0.01). As was predicted from the cross-sectional findings, the mean HDL cholesterol levels of women who gave up employment and became full-time homemakers during the follow-up period decreased by 3.04 mg/dl (p less than 0.01), whereas homemakers who became employed showed no significant change in HDL cholesterol levels. The change in mean HDL cholesterol of employed women who had become homemakers could be explained in part by changes in alcohol consumption and in number of pregnancies. The authors conclude that giving up employment is related to life-style changes that are associated with a decrease in HDL cholesterol levels. Furthermore, the findings suggest that employment may exert a beneficial influence on coronary risk in women that is consistent with a positive association between employment and HDL cholesterol. PMID- 1736663 TI - Corroboration of sexual histories among male homosexual couples. AB - Using data from a study of human immunodeficiency virus transmission among homosexual male partners from Boston, Massachusetts, the authors compared self reported sexual histories among 155 index-partner pairs during 1985-1988. Overall, high levels of agreement were observed for all reported sexual activities. Agreement on anal sex was very high (Spearman's r = 0.78-0.79, p less than or equal to 0.001; kappa = 0.76-0.88, p less than or equal to 0.001). Level of agreement did vary significantly by a couple's drug and alcohol use; the heavier substance user generally reported fewer sexual encounters than the lighter user. These results have important implications in sexual behavior research and show that among homosexual men, self-reports of sexual behavior may be reasonably valid. PMID- 1736664 TI - Effects of nondifferential exposure misclassification in ecologic studies. AB - Although many authors have argued against inferring individual-level exposure disease relations from ecologic data because of the potential "ecological fallacy." the availability of data from diverse populations promotes the continued use of this rapid and inexpensive study design. In ecologic studies, the exposure status of groups is often defined by the proportion of individuals exposed. In these studies, nondifferential exposure misclassification of individuals is shown to produce overestimation of exposure-disease associations that may be extreme when the ecologically derived rate ratios are applied to individuals. This overestimation contrasts with the bias toward the null resulting from nondifferential misclassification of a binary exposure in epidemiologic studies conducted at the individual level. Given the magnitude of the potential bias from nondifferential exposure misclassification and other sources, quantitative estimates of individual-level rate ratios from ecologic data should be interpreted with extreme caution. PMID- 1736665 TI - Tests for trend and dose response: misinterpretations and alternatives. AB - Tests for overall trend, such as the Mantel extension test, are not tests for monotonic dose response. A survey of epidemiologic articles shows widespread misinterpretation of the Mantel extension test and overstatement of evidence for monotonic dose response when there are few exposed subjects. To properly evaluate the hypothesis that risk continues to increase with further increases in exposure, one must examine several statistics and estimates. Given sufficient data, nonparametric or polynomial regression analyses can provide more detailed dose-response information. PMID- 1736666 TI - American Journal of Occupational Therapy--Buyers Guide, 92. PMID- 1736667 TI - Cranial capacity evolution in Homo erectus and early Homo sapiens. AB - This paper investigates patterns of cranial capacity evolution in Homo erectus, early Homo sapiens, and in regional subsamples of H. erectus. Specifically, models explaining evolution of cranial capacity in these taxa are evaluated with statistical techniques developed for the analysis of time series data. Regression estimates of rates of evolution in cranial capacity are also obtained. A non parametric test for trend suggests that cranial capacity in both H. erectus and early H. sapiens may increase significantly through time. Cranial capacity in an Asian subsample of H. erectus (comprised of Chinese and Indonesian specimens) increases significantly through time. Other subsamples of H. erectus (African, Chinese, and Indonesian) do not appear to increase significantly through time. Regression results generally corroborate results of the test for trend. Spatial and temporal variation may characterize evolution of cranial capacity in H. erectus. Different patterns of cranial capacity evolution may distinguish H. erectus from early H. sapiens. PMID- 1736668 TI - Brief communication: the popliteal sesamoid bone (cyamella) in primates. AB - A study of 246 adult nonhuman primates belonging to 34 genera indicates that a popliteal sesamoid bone is always present in the tendon of the popliteus muscle in Prosimii and Callitrichidae. The bone occurs only variably in Atelidae and Pongo, and is usually absent in Gorilla. The bone is absent, or very rare, in Cebus, Cercopithecidae, Hylobatidae, Pan, and humans. When the bone is present, it articulates with the posterior part of the articular surface of the lateral condyle of the tibia, and lies very close to the head of the fibula, at the angulated part of the popliteal tendon, near the tendomuscular junction. The presence of the popliteal sesamoid bone in primates is a primitive character. PMID- 1736669 TI - Brief communication: histological age estimation using rib and clavicle. AB - Histological methods for estimating age at death using osteon population densities for the rib, clavicle, and rib and clavicle combined are presented. Predicting formulas were generated from a sample of 40 individuals of known age, sex, and race. Independent samples of 12 ribs and 7 clavicles were used to test the formulas. Mean differences between known and predicted ages were 1.1 years, 2.6 years, and 3.4 years for the clavicle, rib and clavicle combined, and rib formulas respectively. An analysis of variance found no significant differences among the means for predicted and known ages. Since the formula based upon rib and clavicle combined has the higher standard error and r2, and includes data from different bones, it should provide better overall accuracy and reliability, and is recommended whenever both bones are available. PMID- 1736670 TI - Obituary: Frederick S. Hulse, 1906-1990. PMID- 1736671 TI - Reassessment of the paleoenvironment and preservation of hominid fossils from Hadar, Ethiopia. AB - Samples of paleosols from locality AL-333, known for numerous specimens of Australopithecus afarensis, were analyzed in order to reconstruct the original soils and environment of burial of the associated fossil hominids. The bones were found in swale-like features, within the calcareous and coarse-grained basal portion of a paleosol. This is more like an assemblage of bones buried during a single depositional episode, such as a flood, than an assemblage accumulated on a soil over a long period of time by carnivores or other means of death. What killed the hominids remains unclear, but considering the association of originally disarticulated bones of such hydraulically distinct types as phalanges and maxillae, it is very likely that they died and partially rotted at or very near this site. The paleosols at AL-333, here named the Fo and Go clay paleosols, have calcareous rhizoconcretions, granular surface horizons, prismatic peds, and shallow calcareous nodules and stringers like soils now supporting grassy woodland in semiarid regions. Although this group of hominids was buried in streamside gallery woodland, there is evidence from Laetoli, Tanzania, that A. afarensis ventured out into open wooded grassland as well. Evidence for this should be sought from other paleosols at Hadar. PMID- 1736672 TI - Further evidence on relative dental maturation and somatic developmental rate in hominoids. AB - New data on hominoid dental development are presented. Individual bivariate pairings of all mandibular teeth were made for African apes and humans. Data were analyzed with a full linear regression model. No statistically significant differences were found among apes, although a consistent pattern of earlier incisal development was observed in Pan relative to Gorilla. This is concordant with an earlier fusion of the premaxillary:maxillary suture in Pan. Only one tooth pair differed significantly by sex among apes. Two biologically distinct human samples (Libben and Hamann-Todd), although assessed differently (extraction and radiography) yielded virtually identical results. Humans differ from apes only by earlier relative calcification of their anterior teeth. This can be viewed as a consequence of reduced facial prognathism and a shift in hominid canine function. PMID- 1736673 TI - Porotic hyperostosis: a new perspective. AB - Porotic hyperostosis is a paleopathologic condition that has intrigued researchers for over a century and a half. It is now generally accepted that anemia, most probably an iron deficiency anemia, is the etiologic factor responsible for lesion production. Although there can be a number of factors involved in the development of iron deficiency anemia, a dietary explanation has often been invoked to explain the occurrence of porotic hyperostosis in past human skeletal populations. In fact, porotic hyperostosis has been referred to as a "nutritional" stress indicator. Traditionally those groups with a higher incidence of porotic hyperostosis have been considered to be less successful in adapting to their environment or more nutritionally disadvantaged than other groups. A new perspective is emerging that is challenging previous views of the role of iron in health and disease, thus having profound implications for the understanding of porotic hyperostosis. There is a new appreciation of the adaptability and flexibility of iron metabolism; as a result it has become apparent that diet plays a very minor role in the development of iron deficiency anemia. It is now understood that, rather than being detrimental, hypoferremia (deficiency of iron in the blood) is actually an adaptation to disease and microorganism invasion. When faced with chronic and/or heavy pathogen loads individuals become hypoferremic as part of their defense against these pathogens, thus increasing their susceptibility to iron deficiency anemia. Within the context of this new perspective porotic hyperostosis is seen not as a nutritional stress indicator, but as a indication that a population is attempting to adapt to the pathogen load in its environment. PMID- 1736674 TI - On comparing biological shapes: detection of influential landmarks. AB - For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form consists of size and shape. Several approaches for comparing biological forms using landmark data are available. If the two biological forms are demonstrated to be different, the next important issue is to localize the differences by identifying those areas which differ most between the two objects. In this paper we suggest a technique to detect influential landmarks, those which contribute most to the difference between forms. We study the effectiveness of the technique using three dimensional simulated data sets and two examples. Results suggest that the technique is useful in the study of biological form and its variation. PMID- 1736675 TI - Cranial growth in the squirrel monkey (Saimiri sciureus): a quantitative analysis using three dimensional coordinate data. AB - Improvements in data gathering technology have made it possible to quickly and accurately digitize large numbers of objects. The three dimensional coordinates of 44 homologous landmarks were obtained from a sample of 104 squirrel monkey (Saimiri sciureus) crania. After sorting by sex, the crania were assigned to one of four dental age groups. Two quantitative methods, Euclidean distance matrix analysis (EDMA) and finite element scaling analysis (FESA), were used to study craniofacial form change during growth within each sex. Form differences between the sexes at each developmental age were also examined. Both sexes show a small amount of cranial growth overall; however, there are areas of substantial local growth. These areas include the anterior neurocranium and basicranium, the basioccipital, and the anterior palate. Sexual dimorphism in the craniofacial complex is minimal. The most dimorphic regions are the orbitonasal portion of the lower face, the cranial base, and the palate. PMID- 1736676 TI - Positional behavior of Pan troglodytes in the Mahale Mountains and Gombe Stream National Parks, Tanzania. AB - The positional behavior of habituated adult chimpanzees and baboons was observed for 784 hr in a year-long study. Comparisons between species were made to establish the distinctiveness of chimpanzee positional behavior and habitat use. Brachiation (sensu stricto, i.e., hand-over-hand suspensory locomotion) was observed in low frequencies among chimpanzees, and its significance for chimpanzee anatomy is judged slight. Although no significant differences were found between sympatric baboons and chimpanzees in the proportion of time spent in the terminal branches, or in the mean diameter of weight-bearing strata, chimpanzees exhibited evidence of a terminal branch adaptation in that they, unlike baboons, used postures among smaller supporting strata different from those used among larger supports. Among chimpanzees, unimanual arm-hanging was most common among the smallest strata and was associated with smaller mean and median support diameter than other postures. Unimanual arm-hanging was the only common behavior among chimpanzees that usually involved complete abduction of the humerus. A number of behaviors often subsumed under the label "quadrumanous climbing" were distinguished in this study. Compared to baboons and other cercopithecoids, chimpanzees did not show increased frequencies of large-stratum vertical climbing, and their vertical climbing did not involve significant humeral abduction. Arm-hanging (i.e., unimanual suspension) and vertical climbing distinguish chimpanzee positional behavior from that of monkeys. PMID- 1736677 TI - Interactive control of pulsed field gel electrophoresis via real time monitoring. AB - The migration of DNA fragment bands through a slab gel can be monitored by UV absorption at 254 nm and imaged by a charge-coupled device (CCD) camera. Background correction and immediate viewing of band positions to interactively change the field program in pulsed-field gel electrophoresis is possible throughout the run via this detection scheme. The use of absorption removes the need for staining or radioisotope labelling, thereby simplifying sample preparation and reducing hazardous waste generation. This leaves the DNA in its native state and further analysis can be performed without destaining. The optimization of buffer concentration, electric field strength, temperature, agarose concentration, as well as pulse duration can considerably reduce total run time. For example, DNA from 2 to 850 kb can be separated in 3 h on a 7-cm gel with interactive control of the pulse time, which is 10 times faster than using a constant field program. PMID- 1736678 TI - Nitroprusside and methylene blue methods for silicone membrane differentiated flow injection determination of sulfide in water and wastewater. AB - Hydrogen sulfide evolved from an acidified sample is pre-concentrated by permeation in a stationary alkaline acceptor solution enclosed in a silicone rubber sample loop. Depending on the sample volume pre-concentrated, the applicable analytical range spans low micrograms/L to tens of mg/L for both methods. The methylene blue method is more sensitive by a factor of approximately 30 and actually permits practical determinations in the sub-micrograms/L levels. The limit of detection (LOD) for the nitroprusside method ranges from 20 micrograms/L for a 20 microL sample by conventional flow-injection determination (no membrane, throughput 30 samples/h) to less than 2 micrograms/L for 12 mL sample pre-concentrated in the membrane system (throughput 5 samples/h). The membrane is highly resistant to fouling and permits analysis of untreated wastewater samples bearing suspended solids, oil, grease, etc. without any pretreatment. No significant interference is observed with either chemistry. Although the nitroprusside chemistry is less sensitive, it does not involve the use of concentrated aggressive reagents and is recommended unless ultratrace determinations are essential. Viable reaction mechanisms are proposed for both of these chemistries. PMID- 1736679 TI - Dual-field and flow-programmed lift hyperlayer field-flow fractionation. AB - Field and flow programming and their combination, dual programming, are shown to extend the particle size range to which a single flow/hyperlayer field-flow fractionation (FFF) run is applicable to approximately 1-50 microns. The rationale for programming flow/hyperlayer FFF (or other forms of lift hyperlayer FFF) is to expand the diameter range of micron size particles that can be resolved in a single run. By contrast, the reason for programming normal-mode FFF, the only kind of programming previously realized in FFF, is to reduce the analysis time of submicron particle samples of considerable size variability. These differences are explained in detail in relationship to the basic mechanisms governing retention in normal, steric, and lift hyperlayer FFF. Experiments are described in which field, flow, and dual programming are used to expand the accessible diameter range of flow/hyperlayer FFF. An example is shown in which 11 sizes of latex microspheres in the 2-48-microns diameter range are separated by dual programming in 11 min. PMID- 1736680 TI - Distribution and dendritic features of three groups of rat olivocochlear neurons. A study with two retrograde cholera toxin tracers. AB - Cholera toxin B subunit conjugated to horseradish peroxidase, and unconjugated cholera toxin B subunit are useful tools for retrograde tract tracing. Unilateral injection of either cholera toxin preparation into the cochlea results in excellent labeling of olivocochlear neurons, as judged by the Golgi-like filling of cell bodies, dendrites, and even axons. By this approach, we have studied the light microscopic cytology and topographic distribution of olivocochlear neurons and counted their numbers in Sprague-Dawley rats. The olivocochlear system of rats can be divided into three subgroups. The lateral olivocochlear system, composed of small cells located exclusively within the ipsilateral lateral superior olive (relative to the test cochlea), and a medial olivocochlear system, composed of large cells bilaterally dispersed within the ventral nucleus of the trapezoid body, conformed to previous topographic descriptions. A third subgroup of approximately 110 large cells, herein termed shell neurons, was labeled by both tracers, but was not well recognized in previous studies. Shell neurons and their dendrites surround the ipsilateral, and to a much lesser extent the contralateral, lateral superior olive. Lateral olivocochlear neurons do not project their dendrites outside the gray matter of the lateral superior olive, while dendrites belonging to shell neurons penetrate into that nucleus as well as into other auditory brain stem nuclei and the surrounding reticular formation. Medial olivocochlear neurons usually project dendrites ventrally into the trapezoid body and are always excluded from the lateral superior olive. PMID- 1736681 TI - Preferential differentiation of the bile ducts along the portal vein in the development of mouse liver. AB - The development of bile ducts in the mouse liver was studied histochemically, with special reference to their preferential differentiation around the portal vein. Both portal vein and hepatic vein shared a common origin, the omphalomesenteric vein. In the early development of the liver, haematopoietic cells were predominant around both veins. With the progressive development of intrahepatic bile ducts, the following three steps were observed: cluster formation of type I hepatocytes around the portal vein, formation of primitive bile duct structures and basal lamina, then formation of ducts surrounded by connective tissue structures composed of type I and type III collagens and lectin binding sites, which were predominant around the portal vein compared to the hepatic vein. These results suggest that the deposition of abundant connective tissue structures around the portal vein is a prerequisite for the cell differentiation and basal lamina formation in the bile duct precursors. A possible mechanism of the aggregation of type I hepatocytes around the portein vein is also discussed. PMID- 1736682 TI - Afferent organization of the lateral reticular nucleus in the rat: an anterograde tracing study. AB - The organization of the afferent projections to the lateral reticular nucleus of the rat was investigated following placement of horseradish peroxidase-conjugated wheatgerm agglutinin into the red nucleus, fastigial nucleus, various levels of the spinal cord or the sensorimotor area of the cerebral cortex. The pattern of distribution of anterogradely labelled profiles visualized with tetramethylbenzidine revealed that the caudal three-fourths of the lateral reticular nucleus received a large, topographically organized projection from the entire length of the contralateral spinal cord. The lateral part of the rostral half of the lateral reticular nucleus received a small projection from the contralateral red nucleus, the dorsal part of the middle third of the nucleus received a diffuse projection from the contralateral fastigial nucleus, and the extreme rostromedial part of the nucleus received a sparse projection from the contralateral cerebral cortex. The dorsal part of the middle third of the lateral reticular nucleus also received a small projection from the ipsilateral cervical spinal cord. The distribution of afferent fibres from different levels of the spinal cord, red nucleus, and fastigial nucleus overlapped substantially in the middle third of the lateral reticular nucleus, whereas the cerebral cortical receiving area was separate. These data suggest that the middle third of the lateral reticular nucleus integrates spinal and supraspinal impulses to the cerebellum, while the rostral part of the nucleus is involved in a separate cerebral cortico-cerebellar pathway. PMID- 1736683 TI - Intimate apposition of the glomus and smooth muscle cells (g-s connection) in the carotid labyrinth of juvenile bullfrogs. AB - Intimate apposition of the glomus and smooth muscle cells (g-s connection) was found in almost all glomus cells of the carotid labyrinths in juvenile bullfrogs, Rana catesbeiana. There were three types of g-s connection: between thin processes (0.1-0.2 micron in width) without dense-cored vesicles of glomus cells and smooth muscle cells; between thick processes (1.0-1.5 microns in width) with dense-cored vesicles of glomus cells and smooth muscle cells; and between the tongue-like projections of smooth muscle cells and the flat surface of the glomus cell. In some cases, a single glomus cell made g-s connections with several smooth muscle cells. Exocytosis often occurs at the g-s connection. Afferent and efferent synapses were found on the glomus cells with g-s connections. Reciprocal synapses were also observed. On the basis of these findings, the second and third types of g-s connection are presumed to participate in vascular regulation. PMID- 1736684 TI - Morphology of a dicephalic cat. AB - A detailed anatomical study of a dicephalic iniodymic monosomic cat in conjunction with the morphogenetical implications of the observed anomalies is presented. The animal exhibited two heads joined at the level of an anomalous medial exoccipital bone. Two brains and two foramina magna were present. The vertebral column was single but the cranial cervical vertebrae (C2 to C5) had doubled bodies. Cervical rachischisis with myeloschisis were associated defects. Two nasopharyngeal and oropharyngeal cavities converged caudally into a single laryngopharynx. The esophagus, larynx and trachea were single. Duplication of the tongue and hyoid apparatus was present. Palatoschisis affected both oral cavities. Hypoplasia of the anatomical structures in the medial aspects of both heads was observed. Microphthalmia was also observed in both medial eyes. Comparative aspects of the morphology, causative agents, and mechanisms and anomalous morphogenesis of anterior duplications are reviewed and discussed. PMID- 1736685 TI - Meso-diencephalic regions projecting to spinal cord and dorsal column nuclear complex in the hedgehog-tenrec, Echinops telfairi. AB - The distribution of neurons projecting to the spinal cord and dorsal column nuclear complex was investigated in the mesodiencephalic regions of the lesser hedgehog-tenrec, Echinops telfairi (Insectivora) by using the retrograde flow technique. While only few neurons projected to the dorsal column nuclear complex, numerous cells were found to give rise to spinal projections. Rubro-spinal neurons of various sizes were distributed over the entire rostrocaudal extent of the contra-lateral nucleus; a few neurons were also located ipsilaterally, Unlike that of the opossum, the projection appeared to be somatotopically organised. Interstitio-spinal neurons were differentiated into several subpopulations according to their location and laterality of projection. In the ipsilateral periventricular grey, in addition, there was a distinct population of cells possibly corresponding to the nucleus of Darkschewitsch. The mesencephalic central grey contained relatively few labeled neurons, the great majority of them being mesencephalic trigeminal, ectopic cuneiform or midline cells. Labeled cuneiform and midline cells, on the other hand, were quite numerous, extending both from a level just caudal to the trochlear nucleus to levels far beyond the rostral tip of the somatic oculomotor nucleus. The discrepancy between the poorly differentiated oculomotor nuclei and the apparently well-developed Edinger Westphal complex is discussed. Hypothalamo-spinal neurons were essentially restricted to dorsal regions: the hypothalamic paraventricular nucleus (PAV), the dorso-medial (DmHy) and dorso-intermediate cell groups as well as the lateral hypothalamic zone. The latter two cell groups were bilaterally labeled, while the labeled neurons in DmHy and PAV were located predominantly ipsilaterally. Labeled neurons in the amygdala, colliculus superior and mesencephalic trigeminal nucleus were only found following cervical injections; all other mentioned areas and the posterior commissure complex projected to, at least, midthoracic level. PMID- 1736686 TI - Normal colon of Sprague-Dawley rats. An immunohistochemical study. AB - The patterns of expression of the human-tumor-associated antigens, CO17-1A, GA73 3, BR55-2, GICA19-9, CA50 and carcino-embryonic antigen (CEA) were studied in the normal colonic mucosa (the last three also in the serum) of Sprague-Dawley rats. Four immunohistochemically different segments were identified: caecum, ascending colon, transverse colon and descending colon. The immunohistochemical reactions of the cells at the lower part of the crypt were essential for the distinction of the four segments. In the caecum, the MAbs 17-1A, 73-3 and 19-9 stained the glycocalyx of the cells of the lower part of the crypts and the Golgi apparatus of the intercalated cells (IC). MAb55-2 stained very weakly the goblet-like cells (GLC) of the lower part of the crypt of transverse colon, in addition to a nearly complete lack of reaction in the upper part of the crypts. In the ascending colon, the lower part of the crypts showed a characteristic diffuse staining of the intercalated cells with MAb55-2. The perinuclear and mucosal staining observed in the GLC of the transverse colon with MAbs 17-1A, 73-3 and 19-9 as against the supranuclear and Golgi zone staining observed in the GLC/goblet cells (GC)/columnar cells (CC) of the lower part of crypts of the descending colon with the same MAbs, distinguished the former segment from the latter. The IC demonstrated by immunohistochemistry in the lower parts of the crypts of caecum and ascending colon appear to correspond to the replicating cells of the colonic crypts. PMID- 1736687 TI - A direct projection from the medial vestibular nucleus to the cervical spinal dorsal horn of the rat, as demonstrated by anterograde and retrograde tracing. AB - Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin-horseradish peroxidase were iontophoretically injected into different parts of the vestibular nuclear complex (VNC) of the rat. Injections centered into the caudal part of the medial vestibular nucleus revealed a vestibulospinal projection predominantly to the dorsal horn of the cervical spinal cord, besides the expected projection to the intermediate zone (IZ) and ventral horn (VH). While most of the anterogradely labelled fibres could be localized in laminae III to V, some scattered fibres were also seen in laminae I and VI. Lamina II remained free of labelling. The dorsal horn (DH) area with detectable anterograde labelling showed a rostrocaudal extension from C1-C6. Injections into other parts of the VNC labelled fibres and terminals in the IZ and VH while the DH remained almost free of labelling. Additionally, fluorogold and wheat germ agglutinin-horseradish peroxidase were pressure- or iontophoretically injected at different levels into the spinal cord to confirm the projection to the dorsal horn by means of retrograde tracing. Labelled neurons in the area of the medial vestibular nucleus (MVN), from which anterograde labelling in the DH was obtained, were only detectable after fluorogold and wheat germ agglutinin-horseradish peroxidase injections into the cervical spinal cord, in particular its DH. This projection from the caudal medial vestibular nucleus to the dorsal horn of the cervical spinal cord probably enables the VNC to influence sensory processing in the DH, in addition to its well-established influence on posture and locomotion via projections to the intermediate zone and ventral horn. PMID- 1736688 TI - Effect and distribution of intravenously injected 125I-endothelin-1 in rat kidney and lung examined by electron microscopic radioautography. AB - The morphological effect of endothelin-1 (ET-1) and the distribution of endothelin-binding sites on the kidney and lung was investigated ultrastructually by intravenous injection of [125I]-ET-1 into rats. About 10% decrease of the diameter of glomeruli was observed at 10 min after the injections of ET-1 or [125I]-ET-1 (1.3-2.4 nmole/kg). When localization of [125I]-ET-1 in the kidney was examined by light and electron microscopic radioautography, silver grains were preferably localized on the fenestrated endothelial cells of glomeruli and peritubular capillary endothelial cells. Some grains were also localized on the interdigitating processes of urinary tubules. Quantitative analysis of silver grains in the glomeruli showed that 83% of grains were located on the fenestrated endothelial cells, 12% on the podocytes of visceral cells, and 5% on mesangial cells at 10 min. After 60 min, 50% of silver grains were incorporated into the cytoplasm of fenestrated endothelial cells. In contrast to glomeruli, silver grains were rare on the arteries and large arterioles. However, a few silver grains were often observed on the smooth muscle cells of small arterioles (8-20 microns in diameter). In the lung, 70% of silver grains were located on the alveolar capillary endothelial cells. These results indicate the abundance of ET receptors on the glomerular fenestrated endothelium, peritubular fenestrated endothelium and alveolar capillary endothelium. PMID- 1736689 TI - Binding of 125I-endothelin-1 to fat-storing cells in rat liver revealed by electron microscopic radioautography. AB - Localization of intravenously injected [125I]-endothelin-1 was examined in rat liver by light and electron microscopic radioautography. At 10 min after injection, silver grains were localized along the sinusoidal wall, i.e., mostly on the thin processes of fat-storing cells and sinusoidal endothelial cells, and also on the Kupffer cells and the microvilli of hepatocytes. About 35% of the total silver grains were located on the processes of fat-storing cells at 10 min. The grain density (number of silver grains/cell area) of fat-storing cells was three-fold that of Kupffer cells, and 18-fold that of hepatocytes. At 60 min, 60% of the total grains were observed on the fat-storing cells, though the value of grain density was not changed. Silver grains were internalized into the cytoplasm of fat-storing cells and often associated with multivesicular bodies. In contrast, the grain density of endothelial cells and Kupffer cells decreased with time. These results indicate that hepatic fat-storing cells have a considerable number of endothelin-binding sites, and incorporate bound endothelin into cytoplasm. PMID- 1736690 TI - Pediatric transesophageal echocardiography. Present and future. PMID- 1736691 TI - A comfortable hypothesis reevaluated. Cerebral metabolic depression and brain protection during ischemia. PMID- 1736692 TI - Intraoperative echocardiography for evaluation of congenital heart defects in infants and children. AB - To determine the accuracy, utility, and limitations of intraoperative transesophageal echocardiography (TEE) in infants and children, we performed prebypass and postbypass TEE in 90 children undergoing surgical repair of congenital heart lesions, comparing the results to those obtained using intraoperative epicardial echocardiography and pre- and postoperative precordial echocardiography. Patients ranged in age from 4 days to 21 yr (mean 4.1 yr) and in weight from 3 to 68 kg (mean 15.4 kg). Prebypass, we obtained high-quality, two-dimensional TEE images in 86 patients, with correction of the preoperative precordial diagnosis in 3 and confirmation of the preoperative diagnosis in the rest. Adequate epicardial images were obtained in 78 patients, with confirmation of the preoperative diagnosis in all. Shunt lesions that were well delineated prebypass by both TEE and epicardial imaging included interatrial, interventricular, and atrioventricular septal defect lesions. TEE failed to detect the exact size and location of lesions involving the right ventricular outflow tract, i.e., doubly committed subarterial (supracristal) ventricular septal defects. Regurgitant lesions (n = 30) were identified and their severity evaluated in all patients by both TEE and epicardial imaging. Obstructive lesions (n = 33), excluding those involving the right ventricular outflow tract, were well defined by both echocardiographic approaches. Postbypass, we obtained high quality, two-dimensional, color and Doppler TEE images in 86 patients and epicardial images in 78 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736693 TI - Neuropathologic findings after long-term intrathecal infusion of morphine and bupivacaine for pain treatment in cancer patients. AB - Epidural or intrathecal infusions of morphine and bupivacaine mixtures are presently used for the treatment of "refractory" cancer pain even though the neurotoxic potential of such mixtures is unknown. The pathologic findings of the spinal column, the meninges, the nerve roots, and the spinal cord, and the clinical neurologic deficits were recorded in 15 patients (5 men and 10 women), aged 26-83 (median 68) yr, treated for 4-274 (median 81) days with intrathecal infusions of morphine (with preservatives [sodium metabisulfite and sodium edetate]) and bupivacaine mixtures, given through open, subcutaneously tunneled nylon catheters. Six patients had been subjected to radiation therapy (20-96 Gy), applied over the spinal column, and four had been treated with antineoplastics believed to be neurotoxic. Ten patients had various neurologic deficits before the intrathecal treatment. The cumulative doses (ranges) given intrathecally were: morphine 33-11,900 mg, sodium metabisulfite 3.3-1,050 mg, sodium edetate 0.33-105 mg, and bupivacaine 10-41,400 mg; cumulative volumes were 16-9,400 ml. The concentrations of the drugs in the mixtures were: morphine 0.25-4.0 mg/ml, sodium metabisulfite 0.025-0.40 mg/ml, sodium edetate 0.0025-0.04 mg/ml, and bupivacaine 3.0-4.75 mg/ml. The osmolality of the mixtures in vitro ranged from 282 to 286 mOsm/kg and the pH from 4.1 to 4.6. The pathologic findings consisted of vertebral metastases (n = 6), epidural and/or intrathecal tumor masses (n = 8), focal subdural fibrosis (n = 6), infiltration of mononuclear cells in the subarachnoid space (n = 10), and discrete injuries (nerve fiber degeneration or fibrosis) to the anterior (five patients) and posterior (seven) nerve roots, and spinal cord (tumor compression [one], slight thickening of the leptomeninges [one], and thrombosis of a spinal artery and medullary infarction [one]). In none of the cases was any reaction against the nylon catheter within its subarachnoid course recorded. The neuropathologic findings were not related to the duration or cumulative doses of the intrathecal treatment. No new neurologic deficits that could be attributed to the intrathecal administration of the opiate-bupivacaine mixtures were recorded. The neuropathologic and clinical neurologic findings in cancer patients treated with intrathecal morphine-bupivacaine mixtures appeared similar to those in animals and humans reported with either intrathecal morphine or bupivacaine alone. PMID- 1736694 TI - Epidural clonidine after cesarean section. Appropriate dose and effect of prior local anesthetic. AB - Epidurally administered clonidine represents a new approach to postcesarean section pain therapy, yet the appropriate bolus dose and infusion to provide effective pain relief have not been defined. In addition, whether 2 chloroprocaine, a commonly used local anesthetic for intraoperative anesthesia, interferes with clonidine's analgesia, as it does with that of opioids, has not been examined. In this study, using a randomized, blinded design, 63 women received either bupivacaine or 2-chloroprocaine for epidural anesthesia for cesarean section and then received, upon request for analgesia in the recovery room, epidural clonidine 400 micrograms or 800 micrograms bolus, each followed by a 24-h infusion of 40 micrograms/h, or an equivalent volume bolus and infusion of saline. In the bupivacaine group, both clonidine doses produced equivalent analgesia, as determined by pain scores and time to first supplemental intravenous morphine request, and sustained analgesia was produced by clonidine infusion, as measured by need for supplemental morphine. In contrast, 2 chloroprocaine diminished analgesia from 800 micrograms by 21% and abolished analgesia from 400 micrograms clonidine. After 2-chloroprocaine, sustained analgesia from continuous clonidine infusion was present only in the group who had received 800 micrograms clonidine. Clonidine did not alter resolution of residual local anesthetic sensory blockade, as measured by 2- or 4-segment regression following either local anesthetic, but did prolong duration of motor blockade in women receiving bupivacaine. Clonidine produced small decreases in heart rate and blood pressure. One patient received iv fluids for hypotension; one had asymptomatic bradycardia resolving without therapy; and one had mild hypoxemia with snoring during clonidine-induced sedation, responding to supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736695 TI - Intravenous diclofenac coupled with PCA fentanyl for pain relief after total hip replacement. AB - Postoperative pain relief immediately after major surgery cannot be achieved with opioids alone in all patients without respiratory depression or other significant side effects. This investigation was conducted to determine whether the need for opioids and the incidence of side effects can be reduced while maintaining the quality of pain relief using a nonsteroidal antiinflammatory drug as an adjuvant to an opioid. The analgesic efficacy and safety of patient-controlled analgesia using fentanyl with and without intravenous diclofenac were compared after total hip replacement. Forty patients were randomly assigned to receive either diclofenac 75 mg as an initial intravenous loading dose followed by an infusion of 5 mg per hour or saline in a double-blind fashion. The amount of fentanyl administered was recorded. The patients assessed their pain intensity verbally and on a visual analogue scale at intervals of 4 h. The diclofenac group showed a significant reduction in the amount of fentanyl administered during the first 16 h postoperatively as compared to the placebo group (0.65 mg +/- 0.2 vs. 1.08 mg +/- 0.4 respectively, P less than 0.01), and also reported less pain at 16 h (median score on visual analogue scale 0.75 vs. 2.4 respectively, P less than 0.05)). There were no differences in side effects, postoperative blood loss, plasma activated partial thromboplastin time, or Ivy bleeding time between the groups. In conclusion, the addition of diclofenac led to a reduction in fentanyl requirement but did not have any other significant advantages in the treatment of pain following major orthopedic surgery. PMID- 1736696 TI - The accuracy of train-of-four monitoring at varying stimulating currents. AB - Train-of-four (TOF) monitoring of neuromuscular block at submaximal current stimulation has been recommended because it is less painful than monitoring at supramaximal stimulation. The measurement error, however, when using submaximal stimulation has not as yet been fully elucidated. The authors therefore quantified the measurement error of TOF monitoring at low currents near the initial threshold for stimulation (ITS) by assessing precision (the difference between duplicated TOF ratios measured at the same current) and accuracy (the difference between TOF ratios at lesser currents and the TOF ratio at 58 mA, which served as the reference standard method). A stable neuromuscular block at a TOF ratio of 0.40 and subsequently 0.70 was established in 20 patients using a continuous infusion of atracurium. The ulnar nerve was stimulated at the wrist using TOF stimulation, and the evoked twitch response of the adductor pollicis muscle was measured with a force-displacement transducer. The stimulating current was varied in 5-mA steps between ITS and 55 mA. Whereas there were no statistical significant differences between the mean TOF ratios at the different currents, the standard deviation increased with decreasing currents (P less than 0.01 at currents less than 40 mA). The precision was acceptable except at ITS, where the limits of precision (mean intracurrent difference in TOF ratio +/- two standard deviations) exceeded 0.05, which was the chosen acceptable difference. The standard deviation of the accuracy was significantly increased at currents less than or equal to ITS + 25 mA (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736697 TI - Eye injuries associated with anesthesia. A closed claims analysis. AB - Claims against anesthesiologists for eye injuries were analyzed as part of the ASA Closed Claims Project. Eye injury occurred in 3% of all claims in the database (71 of 2,046). The payment frequency for eye injury claims was higher than that for non-eye injury claims (70% vs. 56%; P less than or equal to 0.05). The median cost of eye injury claims was less than that for other claims ($24,000 vs. $95,000; P less than or equal to 0.01). Two distinct subsets were identified. The first was characterized by corneal abrasion during general anesthesia (25 of 71 claims; 35%). Claims for corneal abrasion were characterized by low incidence of permanent injury (16%) and low median payment ($3,000). Reviewers were able to identify a mechanism of injury in only 20% of claims for corneal abrasion. The second subset of eye injury was characterized by patient movement during ophthalmologic surgery (21 of 71; 30%). Blindness was the outcome in all cases. Sixteen of the claims involving movement occurred during general anesthesia, and 5 occurred during monitored anesthesia care. The median payment for claim involving movement was 10 times greater than for non-movement claims ($90,000 vs. $9,000; P less than or equal to 0.01). Anesthesiologist reviewers deemed the care rendered in the general anesthesia "movement" claims as meeting standards in only 19% of claims. From the perspective of patient safety, as well as risk management, these data suggest two specific needs: research directed at better understanding of the etiology of corneal abrasion and clinical strategies designed to assure patient immobility during ophthalmic surgery. PMID- 1736698 TI - Does epidural administration of butorphanol offer any clinical advantage over the intravenous route? A double-blind, placebo-controlled trial. AB - The differential effects of intravenous versus epidural administration of short acting, lipid-soluble opioids is controversial. This study was undertaken to compare these two routes of administration using the mixed agonist-antagonist opioid, butorphanol. Forty-five women undergoing elective cesarean delivery at term under epidural lidocaine anesthesia were randomized to receive a single bolus of either epidural or intravenous butorphanol 2 mg or saline control for postoperative analgesia. At precisely 60 min after the last dose of epidural local anesthetic, all patients received a simultaneous epidural and intravenous injection in a randomized, double-blinded fashion. The intravenous group received butorphanol intravenous and saline epidurally; the epidural group received saline intravenous and butorphanol epidurally; and a control group received saline via both routes. When additional analgesia was requested, all patients received patient-controlled analgesia (PCA) with intravenous morphine (2-mg demand dose, 7 min lockout interval). Analgesia was quantitated using a visual analogue scale and subsequent PCA morphine requirements. The interval from study drug injection until first request for PCA use was equivalent for the intravenous and epidural groups (89 +/- 9 and 83 +/- 8 min, respectively) and significantly longer than in control group (39 +/- 4 min, P less than 0.001, intravenous and epidural vs. control). Analgesia was equivalent in the intravenous and epidural groups at all observation points, and pain scores were significantly lower than control for the first 120 min after study drug injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736699 TI - A comparison of the cerebral protective effects of isoflurane and mild hypothermia in a model of incomplete forebrain ischemia in the rat. AB - The present study was undertaken to examine the cerebral protective properties attributed to isoflurane and at the same time to compare its protective effects with those of mild hypothermia (temperature reduction by 3 degrees C). Twenty-one fasted Wistar-Kyoto rats were assigned to one of three groups (n = 7); 1.3 MAC (end-tidal) isoflurane-normothermia (pericranial temperature 38.0 degrees C), 1.3 MAC halothane-normothermia, and 1.3 MAC halothane-hypothermia (pericranial temperature 35.0 degrees C during ischemia). In each animal the trachea was intubated and the lungs were mechanically ventilated. Each animal was subjected to temporary incomplete forebrain ischemia induced by 10 min of bilateral carotid artery occlusion with simultaneous hypotension (mean arterial pressure 35 mmHg) induced by trimetaphan and blood withdrawal. After a 3-day survival period, perfusion-fixation was performed, and two blinded observers assessed histopathologic injury according to a four-point scale (0 = no damage; 1 = less than 10% of neurons damaged; 2 = 10-50% damaged; and 3 = greater than 50% damaged). The assessment was performed at two points in the rostrocaudal axis chosen to permit evaluation of regions with varying levels of ischemic damage. In the rostral sections, in the isoflurane- and halothane-normothermia groups, moderate to severe injury was observed in striatum, cerebral cortex, hippocampus (CA1 and CA3 areas), and reticular nucleus of the thalamus (e.g., the median scores for the CA1 area were 3 in both the halothane-hypothermia and the isoflurane-normothermia groups), and there were no differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736700 TI - Halothane changes the relationships between lung resistances and lung volume. AB - The authors hypothesized that relaxation of airway smooth muscle by halothane lessens the dependence of airway resistance on lung volume, and that halothane alters the relationship between pulmonary resistance and lung volume by changing both the airway and tissue components of pulmonary resistance. The relationship among airway resistance, tissue resistance, and lung volume was examined in mongrel dogs before and during the administration of halothane, both in airways with reduced smooth muscle tone (after vagotomy) and during moderate increases in smooth muscle tone caused by vagus nerve stimulation (VNS). Resistance were measured at several levels of positive end-expiratory pressure (PEEP, 4-15 cmH2O) using an alveolar capsule technique. Before halothane administration, airway resistance increased at low PEEP; VNS accentuated this increase. Tissue resistance increased at low PEEP only during VNS. Halothane had no significant effect on any resistance before VNS. During VNS, halothane markedly blunted increases in airway resistance and tissue resistance as PEEP decreased. The authors conclude that during stimulation of airway smooth muscle in dogs, halothane attenuates increases in airway resistance and tissue resistance with reductions in lung volume in dogs. Thus, moderate changes in lung volume have little effect on these resistances during halothane anesthesia under these conditions. PMID- 1736701 TI - The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. AB - This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736702 TI - Transcranial electrical stimulation with Limoge's currents decreases halothane requirements in rats. Evidence for the involvement of endogenous opioids. AB - Transcutaneous cranial electrical stimulation with Limoge's currents has been shown to facilitate anesthesia/analgesia in surgical patients. However, the neurobiologic substrate of this effect remains unknown. The present study was designed to analyze the influence of transcranial electrical stimulation (TCES) on halothane requirements in rats and the contribution of the central endogenous opioid, alpha 2-adrenergic and 5-hydroxytryptamine (5-HT1 and 5-HT2) serotonergic systems to this effect. The influence of TCES on the MAC of halothane (MACH) and its reversibility by a subcutaneous 2 mg/kg naloxone injection were first determined in 20 rats using a randomized blinded protocol. MACH was decreased markedly in stimulated animals (TCES, n = 10) in comparison with sham-operated nonstimulated rats (controls, n = 10): MACH = 0.60 +/- 0.15, mean +/- SD, versus 1.07 +/- 0.05 vol%, P less than 0.001. In TCES animals, naloxone administration restored MACH values to the levels of controls but failed to affect MACH in controls. The influence of the duration of TCES applied prior to MACH determination was further investigated in 30 animals. The magnitude of MACH reduction was significantly increased with the cumulative duration of stimulation. For each duration of stimulation tested, administration of a 5 micrograms intracerebroventricular (icv) dose of the enkephalinase inhibitor thiorphan significantly enhanced TCES effects (P less than 0.05). Finally, the icv administration of a 15-micrograms naloxone dose appeared to reverse completely the MACH reduction elicited by TCES (n = 8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736703 TI - Coronary microcirculation during halothane, enflurane, isoflurane, and adenosine in dogs. AB - We investigated the effects of clinically administered volatile anesthetics and of adenosine on the microvasculature of the in situ beating canine heart. Thirteen dogs were studied during general anesthesia with an opioid (piritramide), which was infused throughout the experiments. Measurements were obtained in each animal at control (piritramide only) and during hypotension (mean arterial pressure 60 mmHg) induced by halothane, enflurane, isoflurane, and adenosine. Using epiillumination and fluorescence microscopy, 354 arterial microvessels with diameters from 20 to 450 microns were examined through all experimental periods. Hypotension by halothane, enflurane, isoflurane, and adenosine reduced coronary vascular resistance by 13%, 23%, 40%, and 85%, respectively. Coronary venous PO2 was unchanged from control with halothane (+/- 0%) and enflurane (+7%) and significantly increased with isoflurane (+16%) and adenosine (+65%). Left ventricular blood flow decreased significantly during halothane (-35%) and enflurane (-23%); was unchanged from control during isoflurane (-9%); but significantly increased during adenosine (+397%). Coronary arterial and arteriolar diameters increased with all hypotensive agents. Vasodilation was least with halothane, intermediate with enflurane and isoflurane, and most pronounced with adenosine. Diameters increased considerably more in vessels with initial diameters below 100 microns as opposed to larger vessels. Calculation of microvascular segmental resistances revealed that the maximum conductance changes during volatile anesthetics were located in the vessel segments visualized by microscopy, i.e., in vessels larger than 20 microns. However, this was not the case with adenosine. We conclude that volatile anesthetics induce coronary vasodilation by preferentially acting on vessels with diameters from 20 microns to approximately 200 microns, whereas adenosine, in addition, has a pronounced impact on the small precapillary arterioles. PMID- 1736704 TI - Prostaglandin-related microvascular dilation in pentobarbital- and etomidate anesthetized rats. AB - Etomidate is characterized by minimal systemic cardiovascular effects, but its effect on the microvasculature has not been assessed. We compared the microvasculature of etomidate-anesthetized animals to that of animals anesthetized with pentobarbital, since its effects on the microvasculature are known. Male Sprague-Dawley rats were anesthetized with etomidate or pentobarbital. The cremaster muscle was prepared for microscopic viewing, leaving the neural and vascular supply intact. Small arterioles were near their maximal diameters in etomidate-anesthetized rats, whereas the pentobarbital group had a large dilator capacity (maximal diameter-basal diameter/basal diameter). The effect on resting arteriolar diameters of endothelium-derived relaxing factor (EDRF) and prostaglandin synthesis inhibitors was tested. Dilator capacity was not affected by the EDRF inhibitor nitro-L-arginine, but it was significantly increased by mefenamic acid and ibuprofen in etomidate-anesthetized animals. To test whether dilator and constrictor mechanisms were normal, serotonin concentration-response curves were obtained in pentobarbital and etomidate anesthetized animals with and without mefenamate or ibuprofen present. The dilation of small arterioles to serotonin in the etomidate groups with mefenamate or ibuprofen was not significantly different from that of the pentobarbital groups. Serotonin produced a comparable constriction of large arterioles in both anesthetic groups. The topical application of etomidate to the cremaster muscle did not affect arteriolar diameters. Thus, etomidate appears to trigger the release of dilator prostaglandins in striated muscle through a central or indirect mechanism. PMID- 1736705 TI - Left tension pneumothorax mimicking myocardial ischemia after percutaneous central venous cannulation. PMID- 1736706 TI - Postoperative unilateral pulmonary edema: possible amiodarone pulmonary toxicity. PMID- 1736707 TI - Intrathecal fentanyl alleviates spasticity in the presence of tolerance to intrathecal baclofen. PMID- 1736708 TI - Incidental discography during celiac plexus block. PMID- 1736709 TI - Subdural block during attempted caudal epidural analgesia for labor. PMID- 1736710 TI - Epidural alfentanil: is it volume- or concentration-dependent? PMID- 1736711 TI - Discrepancies in upper-limb blood pressure and their impact on internal mammary artery-coronary artery grafting. PMID- 1736712 TI - Symptoms following lumbar puncture may be related to decreased cerebrospinal fluid pressure and/or venous dilation. PMID- 1736713 TI - Airway management with a special tube in an infant with bronchial obstruction. PMID- 1736714 TI - Spontaneous ventilation through transtracheal access. PMID- 1736715 TI - Case report: an unusual reaction to foods? PMID- 1736716 TI - Blood histamine levels following graded cold challenge in atypical acquired cold urticaria. AB - Acquired cold urticaria with a negative cold stimulation test has been described in seven patients in whom the standard ice cube test did not induce localized urticaria. Subsequent total body cold exposure induced a generalized urticaria. A patient with this syndrome is presented where blood histamine levels rose from 9 to 60 micrograms/dL after a negative local cold stimulation test and from 60 to 90 micrograms/dL after total body cold exposure. Urticaria occurred only after generalized cold exposure. Blood histamine levels following the ice cube test may represent a sensitive method to diagnose this form of atypical acquired cold urticaria, without subjecting the patient to the risk of anaphylaxis reported following total body cold exposure. PMID- 1736717 TI - Why mix ROC with RAST? PMID- 1736718 TI - Comparison of skin testing and three in vitro assays for specific IgE in the clinical evaluation of immediate hypersensitivity. AB - A new assay, Pharmacia CAP System (PCS), for allergen-specific IgE (sIgE) was evaluated in 198 new patients presenting with respiratory symptoms to an urban allergy practice. An experienced allergist examined each patient and clinically assessed sensitivity to timothy, short ragweed, Alternaria tenuis, cat, or D. farinae. Puncture and selected intracutaneous skin tests (ST) with these inhalant extracts were then performed. The physician again rated the likelihood of clinical sensitivity to each inhalant, and serum was obtained for sIgE measurements by Phadebas RAST, modified RAST, and PCS. Results of the three in vitro tests (IVT) correlated well with each other and generally agreed with physician assessments and ST results. Individual differences for extracts and assay methods were identified. A few patients with negative ST had positive IVT, but more patients with positive ST were negative by IVT. Modified RAST had greater sensitivity but less specificity than the other two IVT. Analysis of receiver operating characteristic curves showed that sensitivity of the three assays when compared at the 95% level of specificity, did not differ. This result suggests that the cutoff criterion for a positive modified RAST result is too low and should be reevaluated. Skin tests remain the most sensitive and specific test available. The Pharmacia CAP System is a clinically useful assay for sIgE and appears to be a clear advancement for IVT technology. PMID- 1736719 TI - Immunology of diabetes mellitus. AB - Insulin-dependent diabetes is an autoimmune disease that may be becoming more prevalent. It has a polygenic mode of inheritance with a major gene being present in the HLA DQ locus on chromosome 6. Inferential data suggest that environmental factors may be important to genetic penetrance albeit we still lack proof for involvement of often maligned viruses. Patients with IDD and their families are predisposed to organ-specific autoimmunities which should be routinely screened for. Autoantibodies to insulin, to a beta cell cytoplasmic lipid containing moiety and to a beta cell protein of 64KDa, which is believed to be the GABA forming enzyme GAD, can be used to predict IDD among relatives and probably the general population as well. Immunosuppressive therapy can modify the course of IDD after diagnosis and should be able to delay the clinical onset if given before diagnosis. Rigorous insulin therapy should also be given as needed to control hyperglycemia and avoid glucose toxicity to the islets. Such trials are now underway. PMID- 1736720 TI - Thromboxane A2 synthetase inhibitor (OKY-046) improves abnormal mucociliary transport in asthmatic patients. AB - The effect of a thromboxane A2 synthetase inhibitor (OKY-046, 400 mg po/day) on mucociliary transport was investigated in 19 asthmatic patients. The nasal clearance time, as measured by the saccharin test, was prolonged in asthmatics (60.2 +/- 8.4 SE min) compared with normal controls (15.1 +/- 3.4 SE min). Within 4 weeks after OKY-046 administration, the nasal clearance time had improved (27.4 +/- 4.4 SE min, P less than .01) and the amount of sputum had decreased 30% (P less than .01). These results indicate that thromboxane A2 plays an important role in mucociliary transport in patients with asthma. PMID- 1736721 TI - Pentapeptide activity. PMID- 1736722 TI - Influenza vaccine testing in egg sensitive patients. PMID- 1736723 TI - Abstracts presented at the 48th Annual meeting of the American College of Allergy and Immunology. November 16-20, 1991, New York, New York. PMID- 1736724 TI - Withholding and withdrawing life-sustaining therapy. Ethical considerations. PMID- 1736725 TI - Withholding and withdrawing life-sustaining therapy. Practical considerations. PMID- 1736726 TI - The challenge of medical decision making. Balancing patient autonomy and physician responsibility. PMID- 1736727 TI - Reduced forced vital capacity in California grape workers. What does it mean? PMID- 1736728 TI - Reduced FVC among California grape workers. AB - Pulmonary disease due to organic and inorganic dust inhalation represents a significant health problem in the agricultural community. In response to concern over the potential adverse health effects of agricultural exposures, and to address the question of whether the specific crop worked was associated with decreased lung function, we conducted a cross-sectional survey of pulmonary function in a population of 238 grape workers, 355 tomato workers, and 166 citrus workers in California's Central Valley. In addition, 92 workers (66 males and 26 females) performed spirometry before and after an 8-h work shift. Multiple regression analysis of pulmonary function in all 759 workers revealed that age, height, and smoking-adjusted mean preshift FVC was lower in grape workers than in citrus workers in each of three sex and age groups studied: decreased 314 ml for males greater than or equal to 25 yr of age p less than 0.05, 82 ml for males less than 25 yr, and 83 ml for females greater than or equal to 20 yr. Mean adjusted preshift FVC was also lower in grape workers than tomato workers (decreased 249 ml in males greater than or equal to 25 yr [p less than 0.05], 51 ml for males less than 25 yr, and 46 ml for females greater than or equal to 20 yr). Adjusted mean FEV1 was not different by crop, but FEV1/FVC and forced expiratory flow from 25 to 75% of the FVC (FEF25-75) were significantly elevated in grape workers of the three age and sex groups compared with citrus or tomato workers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736729 TI - Relationship of pulmonary function to radiographic interstitial fibrosis in 2,611 long-term asbestos insulators. An assessment of the International Labour Office profusion score. AB - Radiographic evidence of interstitial fibrosis (IF) secondary to asbestos inhalation (using the International Labour Office [ILO] profusion of small irregular opacities) was compared with FVC as an independent indicator of IF. In addition, spirometric indices of airflow (FEV1/FVC and FET25-75%) were correlated with the radiographic profusion score. A study of 2,611 long-term insulators was well designed for these analyses since all subjects were from the same trade, there were sufficient (n = 515) nonsmokers to assess the effects of asbestos exposure in the absence of smoking, most (60%, n = 1,557) of the workers had parenchymal abnormalities (scores greater than or equal to 1/0), and there was a greater prevalence of high scores than in other published series (347 workers or 13.3% had scores greater than or equal to 2/1). Looking at all subjects, the FVC decreased as profusion score increased. The FVC was abnormal (88.0% of predicted) even when the profusion score was clearly normal (0/0). The FVC was lower at any score in smokers and in workers with pleural thickening (more so with diffuse thickening). There was, however, no difference in FVC between intermediate scores 0/1 versus 1/0 and 1/2 versus 2/1. Airflow increased with greater profusion, tending to overcome a decrease seen at lesser profusion scores. These results provide a greater understanding of the relationships among profusion scores, smoking, pleural diseases, and pulmonary function. PMID- 1736730 TI - Epidemiology of infection by nontuberculous mycobacteria. Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum in acid, brown-water swamps of the southeastern United States and their association with environmental variables. AB - Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum (MAIS) organisms were isolated and identified from waters, soils, aerosols, and droplets ejected from water collected from four geographically separate aquatic environments (Okefenokee Swamp, GA; Dismal Swamp, VA; Claytor Lake, VA; and Cranberry Glades, WV) during several seasons. Recovery of MAIS was significantly higher from waters, soils, and aerosols collected from the two acid, brown-water swamps located in the southeastern coastal plain. High MAIS numbers correlated with warmer temperature, low pH, low dissolved oxygen, high soluble zinc, high humic acid, and high fulvic acid. This research, in relation to previous findings for the geographic distribution and physiologic ecology of MAIS, supports the conclusion that waters, soils, and aerosols of the acid, brown-water swamps of the southeastern United States coastal plain represent major environmental sources likely connected with the higher incidence of human infection in this region. PMID- 1736731 TI - Effects of ambient ozone on respiratory function and symptoms in Mexico City schoolchildren. AB - The effects of ambient ozone (O3) on respiratory function and acute respiratory symptoms were evaluated in 143 7- to 9-yr-old schoolchildren followed longitudinally at 1- to 2-wk intervals over a period of 6 months at three schools in Pedregal, Mexico City. The maximum O3 level exceeded the World Health Organization guideline of 80 ppb and the U.S. standard of 120 ppb in every week. For an increase from lowest to highest in the mean O3 level during the 48 hr before spirometry (53 ppb), logistic regression estimated relative odds of 1.7 for a child reporting cough/phlegm on the day of spirometry. For the full population, the mean O3 level during the hour before spirometry, not adjusted for temperature and humidity, predicted a significant decrement in FVC but not in FEV1 or FEF25-75. In contrast, the mean O3 level during the previous 24-, 48-, and 168-h periods predicted significant decrements in FEV1 and FEF25-75 but not in FVC. Ozone was consistently associated with a greater decrement in lung function for the 15 children with chronic phlegm as compared with the children without chronic cough, chronic phlegm, or wheeze. Ozone in the previous 24-, 48-, and 168-h periods predicted decrements in FEV1 for children of mothers who were current or former smokers, but not for children of mothers who were never smokers. Many of these effects were reduced in multiple regression analyses including temperature and humidity, as temperature and O3 were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736732 TI - Respiratory allergy and the relationship between early childhood lower respiratory illness and subsequent lung function. AB - In a study of 159 school-age children whose histories of outpatient visits for lower respiratory illness (LRI) had been documented from early infancy, we observed lower mean levels of small airway function in boys who had experienced two or more episodes of wheezing-associated LRI before 6 yr of age. To determine whether allergy was an important factor influencing this result, we examined relationships among the results of RAST tests for seven common inhalant allergens and concurrent lung function in 126 subjects who consented to venipuncture. Increasing values for the sum of scores for the seven RAST tests were associated with progressively lower mean levels of small airways function in boys with histories of recurrent wheezing LRI during the preschool years. The association of allergy with lower levels of lung function was largely accounted for by dust mite allergy. RAST results were not correlated with lung function in boys who had experienced zero or 1 wheezing LRI before 6 yr of age or in girls. A history of recurrent wheezing LRI during the preschool years was also associated with significantly lower mean levels of small airways function in boys who had negative RAST tests. A subset of 49 boys was reevaluated after an average interval of 4 yr with RAST tests, spirometry, and methacholine challenge. Dust mite allergy was associated with an increased prevalence of bronchial hyperreactivity independent of early childhood wheezing LRI history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736733 TI - Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0.3 ppm nitrogen dioxide. AB - Symptoms and changes in pulmonary function of subjects with chronic obstructive pulmonary disease (COPD) and elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using a double-blind, crossover design with purified air. The 5-day experimental protocol required approximately 2 wk with at least a 5-day separation between randomized 4-h exposures to either NO2 or air which included several periods of exercise. Over a 2-yr period, COPD subjects, all with a history of smoking, consisting of 13 men and 7 women (mean age of 60.0 yr) and 20 elderly normal subjects of comparable age and sex were evaluated. During intermittent light exercise, COPD subjects demonstrated progressive decrements in FVC and FEV1 compared with baseline with 0.3 ppm NO2, but not with air. Differences in percent changes from baseline data (air-NO2) showed an equivocal reduction in FVC by repeated measures of analysis of variance and cross over t tests (p less than 0.10). Subgroup analyses suggested that responsiveness to NO2 decreased with severity of COPD; in elderly normal subjects, NO2-induced reduction in FEV1 was greater among smokers than never-smokers. A comparison of COPD and elderly normal subjects also revealed distinctions in NO2-induced responsiveness. PMID- 1736734 TI - The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group. AB - As part of a multicenter clinical trial (Lung Health Study), methacholine inhalation challenge testing was performed in 5,877 current cigarette smokers, ages 35 to 59 yr (mean 48.5 +/- 6.8 yr), with borderline to moderate airflow limitation (FEV1/FVC ratio 63.0 +/- 5.5). The test was successfully completed in 96.4% of subjects, of whom 63% were male and 95.9% were white. Symptomatic reactions to methacholine were rarely severe enough to require evaluation by a trial physician. Nonspecific airways hyperresponsiveness (AHR) was defined as a greater than or equal to 20% decline in FEV1 from the post-diluent control value after inhalation of less than or equal to 25 mg/ml methacholine. AHR was noted in a significantly higher percentage of women (85.1%) than men (58.9%). Moreover, nearly twice as many women as men (46.6 and 23.9%, respectively) responded to less than or equal to 5 mg/ml of methacholine. In both men and women, baseline degree of airways obstruction and clinical center were strongly associated with AHR (p less than 0.001), whereas age was not. Additional associations with AHR were analyzed in men and women separately using logistic regression after adjustment for baseline lung function, age, and center-to-center differences. In men, AHR was significantly related to symptoms of wheeze, chronic cough and/or sputum, and a history of asthma or hay fever (p less than 0.004), but not to current or lifetime tobacco use. By contrast, among women, AHR was not significantly associated with chronic cough and/or phlegm (p greater than 0.05) or a past history of asthma or hay fever (p greater than 0.1) and was only weakly related to wheeze and current asthma (p = 0.04), as well as to cigarette pack years (p = 0.044). These results indicate that most continuing smokers with functional evidence of early chronic obstructive pulmonary disease have nonspecific AHR that is strongly related to gender and baseline lung function and, to a lesser extent, to respiratory symptoms. The reason for the striking effect of gender on AHR in early chronic obstructive pulmonary disease is unclear but cannot be attributed to male-female differences in age, cigarette use, presence of asthma, or baseline degree of airflow obstruction. PMID- 1736735 TI - Alveolar macrophage content of isoferritins and transferrin. Comparison of nonsmokers and smokers with and without chronic airflow obstruction. AB - Alveolar macrophages (AM) contain iron and ferritin, and concentrations of both are increased in AM of smokers compared with nonsmokers. Ferritin stores iron in a nontoxic form but can release iron in the presence of reducing agents and thereby catalyze the generation of toxic hydroxyl radicals via the Haber-Weiss reaction. Two distinct isoferritins are found in peripheral monocytes, L ferritin and H ferritin. H ferritin is the predominant isoferritin in human monocytes and is more effective than L ferritin in detoxifying iron in vitro. In this study we quantitated content of H and L ferritins, transferrin, and iron in AM recovered by bronchoalveolar lavage (BAL) of 24 subjects, including eight nonsmokers, eight smokers with normal spirometry, and eight smokers with chronic airflow obstruction (CAO). Of total AM ferritin in nonsmokers 95% was composed of L ferritin. Smokers without CAO demonstrated a 6.5-fold increase in the AM content of L ferritin (1,886 +/- 266 versus 290 +/- 51 ng, mean +/- SEM; p less than 0.0001) and a 3.8-fold increase in H ferritin (61 +/- 18 versus 16 +/- 2 ng per 1 x 10(6) AM, p less than 0.01) compared with nonsmokers. Compared with smokers without CAO, AM recovered from smokers with CAO demonstrated a greater increase in L ferritin (5,059 +/- 493 versus 1,886 +/- 266 ng per 1 x 10(6) AM, p less than 0.002) but a similar increase in H ferritin (64 +/- 8 versus 61 +/- 18 per 1 x 10(6) AM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736736 TI - Response of young asthmatic patients to inhaled sulfuric acid. AB - The intent of this study was to explore the effects of inhalation of [H+] defined here as acid airborne particles at near ambient concentrations on the pulmonary function of adolescent asthmatic subjects. During rest and exercise, 22 adolescent asthmatic subjects inhaled atmospheres containing either clean air or sulfuric acid particles (H2SO4) through a mouthpiece. The concentration of hydrogen ion at the mouthpiece ([H+]) ranged from 1.18 to 3.59 mumol/m3 (51 to 176 micrograms/m3 of H2SO4). The lower range of [H+] is near the peak values measured during the summer months in the eastern United States and Canada. Pulmonary function and oral ammonia levels were measured before and after exposure in all subjects. Significant group responses to [H+] were seen in FEV1 (p = 0.016) and FVC (p = 0.039) measured 2 to 3 min post-exposure. Also, the slopes of the change in pulmonary function versus [H+] were computed for each subject. The slopes of changes in FEV1 and Vmax50 and Vmax75 versus [H+] were related to the subject's response to a standard exercise treadmill test, specifically to the subject's percentage decrease in FEV1 after exercise challenge. Pulmonary function changes 20 min postexposure did not show a significant group response to [H+] exposure; however, the relationship between percentage FEV1 decrease after exercise and the individual slopes of Vmax50 and Vmax75 persisted for at least 20 min after exposure. PMID- 1736737 TI - Tumor necrosis factor causes bronchial hyperresponsiveness in rats. AB - We have previously reported that exposure of rats to aerosolized endotoxin (LPS) causes a transient, dose-dependent increase in bronchial responsiveness (BR) to 5 hydroxytryptamine (5HT), 90 min after exposure. In the present study we examined whether LPS induces the release of tumor necrosis factor (TNF) in the airways and whether TNF contributes to the increase in BR. After 90 min following exposure to aerosolized LPS, at a concentration of 1 or 10 micrograms/ml, TNF concentrations in bronchoalveolar lavage (BAL) fluid were 17.9 +/- 6.9 and 80.5 +/- 7.8 U/ml, respectively. No TNF was detected in BAL fluid of saline-exposed animals. At 90 min after exposure to aerosolized recombinant human TNF (rhTNF) (1 microgram/ml) an increase in BR was observed: the provocative concentration of 5HT causing a 50% increase in lung resistance (PC50RL 5HT) was 2.7 +/- 0.4 versus 4.4 +/- 0.3 microgram/kg in saline-exposed animals (p less than 0.01). Pretreatment with anti TNF antibodies 30 min before LPS exposure significantly diminished the increase in BR: PC50RL 5HT was 2.3 +/- 0.4 versus 1.2 +/- 0.5 microgram/kg in control pretreated LPS-exposed rats (p less than 0.01). Exposure to aerosolized TNF also induced a significant influx of neutrophils in BAL fluid (12.1 +/- 3.7 versus 1.7 +/- 0.4% in saline-exposed animals) (p less than 0.01). The LPS-induced neutrophil influx in BAL fluid was partly inhibited by pretreatment with anti-TNF antibodies (55.2 +/- 5.1 versus 76.0 +/- 3.9%) (p less than 0.01). We conclude that TNF causes bronchial hyperresponsiveness and airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736738 TI - Blood gas changes in nonasthmatic rhinitis during and after nonspecific airway challenge. AB - Noninvasive blood gas monitoring is a new, simple, and reliable method for assessing hyperreactivity associated with bronchial asthma. In this study, 104 atopic rhinitic subjects with no history of wheezing and 104 healthy volunteers were challenged with ultrasonically nebulized distilled water (UNDW). Blood gases were monitored transcutaneously (PtcO2 and PtcCO2) over 42 min (20 min for electrode stabilization, 3 min for monitoring a steady baseline, 5 min during UNDW, and 14 min after UNDW). Mean baseline PtcO2 and PtcCO2 values were comparable in the two groups. In rhinitic subjects only, a sudden decrease in PtcCO2 (starting immediately after the beginning of the challenge and maximal 34.7 +/- 0.4 mm Hg SEM versus baseline 41.8 +/- 0.2 SEM mm Hg at the third minute of UNDW exposure) was induced by the challenge and proved significant (p less than 0.001). In the same subjects, a slightly delayed decrease in PtcO2 (starting immediately after the end of UNDW inhalation and maximal 64.5 +/- 1.1 mm Hg SEM versus baseline 78.3 +/- 0.7 SEM mm Hg at 4 min post-UNDW) was also induced by the challenge and proved highly significant (p less than 0.001). The effects of UNDW inhalation on blood gases in normal subjects were negligible and nonsignificant. UNDW in nonasthmatic rhinitis but not in normal subjects gives rise to a sudden hyperventilation and to gas-exchange abnormalities presumably reflecting a ventilation-perfusion mismatching, which, however, is of shorter duration in rhinitic than in asthmatic subjects. PMID- 1736739 TI - Effect of regional alveolar hypoxia on gas exchange in pulmonary edema. AB - We studied the effects of left lower lobe (LLL) alveolar hypoxia on ventilation perfusion (VA/Q) heterogeneity in anesthetized dogs with acute (1-h-old) and mature (24-h-old) permeability pulmonary edema, induced by intravenous administration of 0.05 ml/kg of oleic acid. The left upper lobe was removed and a bronchial divider was placed to allow separate ventilation of the right lung (fraction of inspired oxygen [FIO2] = 1.0) and the LLL (FIO2 = 1.0 or 0.05). Gas exchange was assessed using the multiple inert gas elimination technique. In acute pulmonary edema, LLL hypoxia reduced LLL blood flow and increased true shunt of the LLL compared with a hyperoxic control group. VA/Q heterogeneity of the LLL was markedly increased, indicated by increases in the logarithmic standard deviation of the perfusion distribution (log SDQ) and the retention index of dispersion corrected for shunt (DISPR*). Increases in true shunt and log SDQ were significantly greater than those observed with lobar hypoxia in normal lungs before oleic acid injury. In mature oleic acid injury, LLL alveolar hypoxia resulted in a similar reduction in LLL blood flow and increase in inert gas shunt and DISPR*. We conclude that lobar alveolar hypoxia increased VA/Q heterogeneity of the hypoxic lobe to a greater degree in oleic acid-induced pulmonary edema compared with normal lungs. Phase of oleic acid injury (acute versus mature) did not affect gas exchange during alveolar hypoxia. PMID- 1736740 TI - Regional and systemic oxygen delivery/uptake relations and lactate flux in hyperdynamic, endotoxin-treated dogs. AB - Pathologic oxygen supply dependency (PO2SD) may be etiologic in multisystem organ failure (MSOF) and has been related to mortality in sepsis. Although elevated lactate levels are generally assumed to be a marker of anaerobiosis in these patients, endotoxin may increase serum lactate by inactivation of pyruvate dehydrogenase (PDH), unrelated to tissue PO2. We hypothesized that regional lactate flux may correlate poorly with local oxygen delivery in sepsis. This study examined both the whole-body (WB) and regional (isolated hind limb L and gut G) responses to endotoxin infusion in terms of oxygen delivery, oxygen uptake, and lactate flux in 12 pentobarbital-anesthetized dogs. To separate hypoxia-induced lactate production from that related to inactivation of PDH by endotoxin, half the dogs received dichloroacetate (DCA), a PDH activator. After endotoxin and volume resuscitation, each animal had low systemic vascular resistance with normal to high cardiac output. Despite adequate oxygen delivery to WB, L, and G, arterial lactate levels rose significantly. A 30-min hypoxic challenge (12% FIO2) did not increase lactate levels but did increase WB O2 uptake. DCA normalized lactate levels without influencing oxygen delivery and uptake relations. These data show that lactate levels in endotoxic states may be a poor marker of tissue hypoxia and may be more related to PDH activity. PMID- 1736741 TI - Flow and volume dependence of respiratory system flow resistance in patients with adult respiratory distress syndrome. AB - Using a simple and rapid technique, we studied the flow and volume dependence of the total resistance of the respiratory system (Rrs) in six patients with ARDS. At any given inflation volume, Rrs decreased progressively with increasing flow (V) according to the following hyperbolic function: Rrs = a/V + b, where a and b are constants. At any fixed inflation flow, Rrs increased progressively with increasing inflation volume. The observed flow and volume dependence of Rrs is probably mainly due to the viscoelastic properties of the pulmonary and chest wall tissues. The flow and volume dependence of Rrs found in the patients with ARDS is qualitatively similar to that previously observed in normal anesthetized paralyzed subjects. In ARDS, however, Rrs was considerably greater than in the normal subjects, indicating that besides a low respiratory compliance ARDS is characterized by a high flow resistance. This mainly reflects increased effective flow resistance of the pulmonary and chest wall tissues, although airway resistance is also higher than normal. PMID- 1736742 TI - Resolution of laryngeal injury following translaryngeal intubation. AB - Translaryngeal intubation (TLI) causes mucosal ulcerations of the vocal cords and posterior laryngeal commissure. Usually these ulcers heal by primary reepithelialization, but occasionally laryngeal granulomas or strictures develop at these ulcer sites. The incidence of granuloma and stricture formation and the variables influencing abnormal laryngeal healing following TLI are not well understood. A group of 54 patients who experienced prolonged TLI were followed prospectively to determine the resolution rate of laryngeal injury. Direct fiberoptic laryngoscopy was performed at either extubation or tracheostomy and repeated every 2 wk until the larynx returned to normal or a persistent laryngeal abnormality was identified. Laryngeal symptoms were assessed at these same time points. In 5 patients (9%) the appearance of the larynx was normal at extubation, and in 42 patients (78%) laryngeal healing occurred by primary reepithelialization within 8 wk. Four patients (7%) developed laryngeal granulomas, which required surgical removal in all but one case. No patients in this series developed laryngeal strictures. Three patients (6%) died before complete follow-up. Laryngeal symptoms, particularly hoarseness, resolved as the larynx healed. Performance of tracheostomy, age, TLI for more than 10 days, and severe laryngeal injury at extubation did not influence the median time to resolution of laryngeal abnormalities. Abnormal laryngeal healing following TLI is uncommon but is not exacerbated by prolonged TLI (more than 10 days), severe laryngeal injury at extubation, or performance of a tracheostomy. PMID- 1736743 TI - Efficacy of nocturnal nasal ventilation in patients with restrictive thoracic disease. AB - We tested the efficacy of nocturnal nasal ventilation (NNV) using the BIPAP ventilator in patients with restrictive thoracic diseases by withdrawing them from NNV for an average of 1 wk. One male and five female patients were enrolled in the study; four with restrictive chest wall diseases, and two with muscular dystrophies. All patients had chronic CO2 retention (PaCO2 greater than 50 mm Hg) and had been improved by using NNV for at least 2 months before the study. Four patients were switched to the BIPAP ventilator from standard portable volume ventilators at least 1 month prior to the study without changes in gas exchange or symptoms. After withdrawal of NNV, patients had no deterioration in daytime vital signs, pulmonary functions, maximal inspiratory or expiratory pressures, or arterial blood gases compared with measures made immediately before withdrawal and 1 wk after resumption. However, patients had more dyspnea at rest, increased daytime somnolence, more morning headaches, less daytime energy, and felt less rested in the morning during withdrawal of NNV. Furthermore, nocturnal monitoring demonstrated greater tachycardia, tachypnea, oxygen desaturation, and hypoventilation during withdrawal of NNV. We conclude that NNV administered by the BIPAP ventilator is effective in ameliorating nocturnal hypoventilation and daytime symptoms in patients with chronic CO2 retention caused by severe restrictive thoracic diseases. These data also suggest that the efficacy of NNV may depend more on amelioration of nocturnal hypoventilation than on resting of ventilatory muscles. PMID- 1736744 TI - Effect of breathing pattern and level of ventilation on pulmonary fluid filtration in dog lung. AB - The effect of breathing pattern and level of ventilation on fluid filtration in the lung under edema forming conditions was studied in an in situ left upper lobe (LUL) canine preparation. LUL weight was continuously monitored. In Group 1, rate of edema formation (delta W/delta t) was measured In seven dogs at two vascular pressures (35 and 45 mm Hg) while the LUL was randomly ventilated under six conditions. At equivalent vascular pressures and mean airway pressures (Paw) (and hence, mean operating lung volume), increasing respiratory frequency (f) enhanced delta W/delta t. This was reversed when minute ventilation (VE) was returned to baseline by reducing tidal volume (VT), even when Paw were matched to baseline. Increasing VT also enhanced delta W/delta t whether VE was increased (J Appl Physiol 1988; 64:1900) or not (present study) and whether Paw was matched to baseline. In Group 2 delta W/delta t was measured at fixed VT and f while inspiratory/expiratory time ratio (TI/TE) was switched from 1:1 to 1:6. Shortening inspiratory time by increasing inspiratory flow rate had no effect on delta W/delta t. We conclude that increasing VE, whether by raising VT or f, promotes greater edema formation by mechanisms that are independent of vascular pressure or operating lung volume. Increasing VT appears to have an additional adverse effect over and above that of increased VE. PMID- 1736745 TI - Cardiac output response to continuous positive airway pressure in congestive heart failure. AB - The effects of nasal continuous positive airway pressure (CPAP) were examined during cardiac catheterization in 22 patients with congestive heart failure (CHF). CPAP was applied at a level of 5 cm H2O pressure. Hemodynamic measurements were made at baseline and while on CPAP. We hypothesized that patients with high left ventricular (LV) diastolic pressures would experience an increase in cardiac index (CI). To test this hypothesis, patients were divided into two groups based on their baseline pulmonary capillary wedge pressure (PCWP): one group of 11 whose PCWP was greater than or equal to 12 mm Hg (high-PCWP group) and a second group of 11 whose PCWP was less than 12 mm Hg (low-PCWP group). Among the high PCWP group (mean PCWP +/- SEM = 19.0 +/- 2.7 mm Hg), CI rose significantly while on CPAP (from 2.48 +/- 0.26 to 2.82 +/- 0.26 L/min/m2, p less than 0.01). Stroke volume index (SVI) also rose significantly (from 52.6 +/- 7.0 to 64.1 +/- 8.0 ml/m2, p less than 0.001). In contrast, among the low-PCWP group (PCWP = 8.3 +/- 0.6 mm Hg), CI decreased significantly while on CPAP (from 3.14 +/- 0.44 to 2.89 +/- 0.62 ml/m2, p less than 0.025). SVI fell but not significantly while on CPAP (from 75.5 +/- 8.4 to 74.2 +/- 8.5 ml/m2). Multiple stepwise linear regression analysis revealed that the only significant correlate of the magnitude of change in CI in response to CPAP was baseline PCWP (r = 0.50, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736746 TI - Lipid content of alveolar lining material collected by bronchoalveolar lavage. Improved methods for measuring the major lipid classes. AB - Current methods for measuring lung lipids obtained by bronchoalveolar lavage are time consuming and require sample extraction with organic solvents. Here we utilized enzymatic methods for measuring the major phospholipid classes found in human bronchoalveolar lavage fluid (BALF), namely phosphatidylcholine and phosphatidylglycerol, as well as the neutral lipid cholesterol. These assays can be carried out on as little as 200 microliters lavage fluid in 96-well microtiter plates without the need for organic solvents. Results were verified by comparison with HPLC and chemical methods. The measured values by all three methods were in agreement with previous studies in which lipid analysis was performed by thin layer chromatography. By contrast to thin-layer chromatography, however, the methods described here can be efficiently performed with small quantities of material without sacrificing accuracy. This methodology can facilitate the characterization of the major surfactant-associated lipids in BALF and foster improved understanding of the role of these lipids in human lung disease. PMID- 1736747 TI - Polyethylene glycol-conjugated superoxide dismutase attenuates septic lung injury in guinea pigs. AB - Reactive oxygen species (ROS), including superoxide anions, play an important role in mediating acute lung injury. We examined whether polyethylene glycol conjugated superoxide dismutase (PEG-SOD) attenuates lung injury in Escherichia coli-treated guinea pigs. Twenty-four guinea pigs were divided into four groups: (1) control group; (2) septic group, in which live E. coli (2 x 10(9)/kg) were injected intravenously; (3) pretreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 15 min before E. coli; and (4) posttreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 30 min after E. coli. Lung injury was assessed by the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P), lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid. Plasma half-life of PEG-SOD in normal guinea pigs was 13.5 h. L/P, lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid decreased in both pretreatment and posttreatment groups compared with the septic group. BAL/P decreased in the pretreatment group but not in the posttreatment group compared with the septic group. After the animal model studies, we investigated the effect of PEG-SOD on the human neutrophil extracellular generation of ROS stimulated by phorbol myristate acetate (PMA) in lucigenin-dependent chemiluminescence (CL). PEG-SOD at concentrations greater than or equal to 0.1 U/ml inhibited PMA-induced CL in a dose-dependent manner. We also examined the effect of PEG-SOD on the neutrophil intracellular generation of ROS using flow cytometry to assess intracellular hydroethidine oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736748 TI - Characterization of colony stimulating factor activity in the human respiratory tract. Comparison of healthy smokers and nonsmokers. AB - The number and function of pulmonary macrophages are critical to lung homeostasis. To characterize factors normally present in the human respiratory tract that can influence these parameters, bronchoalveolar lavage (BAL) fluid obtained from healthy smokers and nonsmokers was assayed for the presence of colony-stimulating factor (CSF) activity. Concentrated BAL fluid from both populations was capable of inducing incorporation of [3H]thymidine by murine macrophages. The mean increase (+/- SEM) in incorporation over control cultures not exposed to BAL fluid was 0.98 +/- 0.22 for nonsmokers and 2.25 +/- 1.19 for smokers (p less than 0.001). This CSF bioactivity was characterized as macrophage CSF (M-CSF) by virtue of its action on murine macrophages, the detection of M-CSF protein by a specific ELISA assay, and the inability to detect other macrophage active CSFs, granulocyte macrophage-CSF (GM-CSF) and interleukin-3 (IL-3), in a proliferation assay employing the MO7E cell line. There was a significant correlation between macrophage number in BAL samples and measureable bioactivity among both smokers and nonsmokers (r = 0.763; p less than 0.001). This suggested that macrophages themselves are a source of the M-CSF detected in BAL fluid. To examine this possibility, slot-blot analysis of macrophage RNA was performed. Constitutive expression of comparable amounts of M-CSF mRNA and protein was found in cells from both smokers and nonsmokers. However, macrophages obtained from a randomly selected subset of four smokers but none of five nonsmokers exhibited increased production of M-CSF in response to an inflammatory stimulus, lipopolysaccharide (LPS; 5 ng/ml). M-CSF added to macrophage cultures was degraded by nonsmokers' cells as expected over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736749 TI - Influence of cigarette smoking on bronchoalveolar lavage cellularity in asbestos induced lung disease. AB - To investigate the influence of cigarette smoking on bronchoalveolar lavage (BAL) cellularity in asbestos-induced lung disease, we compared BAL cells in asbestos exposed, nondiseased subjects (n = 20) with those with either asbestosis (n = 25) or asbestos-induced pleural fibrosis (n = 28). Patients with asbestosis (ILO greater than or equal to 1/0) had higher concentrations of BAL macrophages (p = 0.04), neutrophils (p = 0.003), and eosinophils (p = 0.01), while patients with asbestos-induced pleural fibrosis (circumscribed plaques and diffuse pleural thickening) had higher concentrations of BAL lymphocytes (p = 0.02). Within our study population, however, cigarette smoking (smoking status or pack-years of smoking) was strongly associated with BAL macrophages, neutrophils, and eosinophils but was not associated with the concentration of BAL lymphocytes. Using multivariate analysis, we found that although asbestosis remained associated with higher concentrations of BAL macrophages, neutrophils, and eosinophils, cigarette smoking had a far greater contribution to the concentrations of BAL macrophages and eosinophils than did asbestosis. Although cigarette smoking accounted for 17 to 18% of the variance of BAL macrophages and eosinophils, asbestosis was associated with approximately 6% of the variance associated with these cells. In contrast, the concentration of BAL neutrophils remained associated with asbestosis and was not influenced by smoking behavior. We conclude that cigarette smoking strongly influences BAL cellularity (macrophages and eosinophils) in our patients with asbestosis but does not appear to affect the type or concentration of BAL cells in patients with asbestos induced pleural fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736750 TI - Decreased intrapulmonary killing of Mycoplasma pulmonis after short-term exposure to NO2 is associated with damaged alveolar macrophages. AB - Previous studies have shown that exposure of pathogen-free C57BL/6N mice to 5 or 10 ppm NO2 increases the severity of murine respiratory mycoplasmosis and that this effect is associated with decreased intrapulmonary killing of Mycoplasma pulmonis. The purposes of the present studies were to determine the effects of doses of NO2 lower than 5 ppm on pulmonary clearance and to provide experimental links between NO2 exposure, defects in intrapulmonary killing, and alterations in alveolar macrophages. Exposure to less than 5 ppm NO2 had no effect on intrapulmonary killing of M. pulmonis. Bronchoalveolar lavage cells killed M. pulmonis in vitro only if they were allowed to associate with mycoplasmas in vivo. Prior exposure to NO2 abrogated killing in this in vivo-in vitro model. More than 95% of the BAL cells were macrophages, and more than 98% of the cell associated mycoplasmas were on or in alveolar macrophages. Immediately after exposure, the viability of alveolar macrophages was 89 +/- 4% in the control group, 56 +/- 19% in the group receiving M. pulmonis alone, 23 +/- 7% in the group receiving 10 ppm NO2, and 16 +/- 6% in the group receiving both M. pulmonis and NO2 exposures. Viability was significantly decreased following exposure to 10 and 5 ppm NO2 but not following exposure to 2 ppm. Both viability and intrapulmonary killing were depressed at 3 days after exposure to NO2 but were normal by 7 days after exposure. The cellular target of NO2 exposure in relation to intrapulmonary killing of M. pulmonis appears to be the alveolar macrophages. PMID- 1736751 TI - Evidence for in vivo generation of cytotoxic T cells. PPD-stimulated lymphocytes from tuberculous pleural effusions demonstrate enhanced cytotoxicity with accelerated kinetics of induction. AB - Mycobacterium tuberculosis is a bacterial pathogen capable of survival and replication within human macrophages. Cytotoxic T cells are thought to be important for the eradication of infected macrophages. To test this hypothesis, pleural effusion lymphocytes from patients with tuberculous pleuritis were stimulated in vitro with PPD, and proliferation and cytotoxicity were assessed by thymidine incorporation and chromium release, respectively. The level and kinetics of generation of antigen-specific cytotoxicity were measured and compared with those in autologous peripheral blood, control peripheral blood, and nontuberculous effusions. Both proliferation and cytotoxicity in tuberculous pleural effusions were augmented and accelerated in comparison to autologous or control peripheral blood. By contrast, low levels of cytotoxicity were observed in nontuberculous effusions, without evidence of accelerated kinetics. Cell subset fractionation by panning indicated that the cytotoxicity was mediated by CD4+ cells. The accelerated kinetics of induction of PPD-specific cytotoxic T cells demonstrated here suggests reactivation of in vivo generated cytotoxic T cells. These findings provide evidence that cytotoxic T cells are induced at the site of pathology in vivo and suggest that these cells play an important role in protection in vivo against infection with tuberculosis. PMID- 1736752 TI - Combined toxicity of zidovudine and antituberculosis chemotherapy. AB - Because antituberculosis agents and zidovudine are commonly used in HIV-infected patients, we performed a cohort study to determine the toxicity of such combined therapy. A group of 24 consecutive human immunodeficiency virus (HIV)-infected patients with tuberculosis who received concomitant antituberculosis therapy and zidovudine (tuberculosis group) were compared with 24 patients who received zidovudine but not antituberculosis medications (comparison group). Comparison patients were matched to tuberculosis patients by age, sex, ethnic group, month of starting zidovudine, and CD4 cell count. Most tuberculosis patients received isoniazid, rifampin, pyrazinamide, and ethambutol initially, followed by isoniazid and rifampin for a mean total duration of 8.4 months. Baseline clinical and laboratory parameters in tuberculosis and comparison patients were similar, except for the mean hemoglobin (11.2 g/dl in tuberculosis patients versus 12.9 g/dl in comparison patients, p = 0.03). The mean zidovudine dose in tuberculosis and comparison patients was approximately 500 mg/day, and the mean duration of zidovudine therapy was 10.3 and 9.6 months, respectively. Symptoms occurred during therapy with similar frequency in both groups. The frequency and severity of leukopenia and granulocytopenia were similar in tuberculosis and comparison patients, but marked anemia (hemoglobin less than 9.5 g/dl) developed in 50% of tuberculosis patients and 17% of comparison patients (p = 0.03). The maximum decrease in hemoglobin during therapy was similar in both groups (mean of 2.0 versus 1.6 g/dl, respectively), suggesting that the higher frequency of marked anemia in tuberculosis patients was due to their lower baseline hemoglobin values. Although transfusions were required in five tuberculosis patients and one comparison patient, zidovudine was not permanently discontinued in any patient because of anemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736753 TI - Effect of clonidine in obstructive sleep apnea. AB - The current treatment of choice for obstructive sleep apnea is continuous positive airway pressure. However, not all patients tolerate this form of therapy. We evaluated the effect of clonidine hydrochloride, an alpha 2 adrenergic agonist with REM-suppressant activity, in eight male patients with obstructive sleep apnea. In each patient, sleep-stage distribution and breathing pattern in two all-night sleep studies performed during a 10-day course of clonidine were compared with those of two control and two placebo nights. A dose of 0.2 mg of clonidine administered orally at bedtime totally suppressed REM sleep in two patients. In the other six patients, the same dose decreased percent time spent in REM sleep from a control of 13.4 +/- 1.0 to 8.6 +/- 1.4% (mean +/- SEM, p less than 0.05). The latency to REM sleep increased in the latter group from a control of 129 +/- 9 to 308 +/- 24 min (p less than 0.001). Clonidine had no effect on the frequency and duration of non-REM breathing abnormalities. Under clonidine, the level of nocturnal hypoxemia improved in six patients. This was due to a total suppression of REM and the consequent lack of REM apneas in two patients. In four patients, upper airway obstruction disappeared during period of unsuppressed REM sleep, and SaO2 remained above 90% throughout this sleep stage. Clonidine transformed the pattern of sleep-disordered breathing during unsuppressed REM in the other two patients from that of repetitive obstructive hypopneas associated with persistent hypoxemia to occlusive apneas and cyclical hypoxemia. These results were observed consistently in all patients during both clonidine-sleep studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736754 TI - Studies in the genetics of obstructive sleep apnea. Familial aggregation of symptoms associated with sleep-related breathing disturbances. AB - Previous studies of single families have suggested that familial factors may be important in the pathogenesis of obstructive sleep apnea. In this report, the role of inheritance in obstructive sleep apnea was assessed by quantitating the degree of familial clustering of symptoms associated with sleep-related breathing disorders. In total, 272 subjects from 29 families identified through an index case with obstructive sleep apnea and 21 control families with no relative known to have sleep apnea were studied with questionnaires that ascertained health status and symptoms. The unadjusted odds ratios of habitual or disruptive snoring, breathing pauses, and excessive day-time sleepiness in subjects with a single relative with the same symptom were 1.40 to 1.53 (p less than 0.05). Odds ratios increased progressively for subjects with increasing numbers of symptomatic relatives). Adjustment for body mass index, age, and gender modestly reduced these odds ratios to 1.33 to 1.42. These data suggest a significant familial aggregation of symptoms associated with sleep-disordered breathing that appears independent of familial similarities in weight. PMID- 1736755 TI - Effect of ethanol on the arousal response to airway occlusion during sleep in normal subjects. AB - The effect of ethanol on the arousal response to airway occlusion during non rapid eye movement sleep was studied in normal male subjects by testing the response to the occlusion of a face mask covering the nose and mouth on a control (C) and an ethanol (E) ingestion (2 ml/kg of 50% vodka) night in random order. In part A, five subjects breathed room air while in part B another five subjects breathed a mixture of air and oxygen adjusted to maintain a baseline sleeping SaO2 of 98%. In both parts, the time to arousal (TTA) was significantly longer on E nights. The TTA (mean +/- SEM) in part A on C versus E nights was 14.6 +/- 1.9 versus 20.6 +/- 1.4 s in stage 2 and 19.9 +/- 1.9 versus 29.2 +/- 1.8 in stage 3/4 (p less than 0.01). The corresponding values in part B were 22.2 +/- 3.6 versus 39.9 +/- 8.4 in stage 2 and 32.1 +/- 4.1 versus 63.7 +/- 9.6 in stage 3/4 (p less than 0.01). In part B, the maximum deflections in airway pressure were measured at a supraglottic location during airway occlusion to reflect the degree of inspiratory effort. The maximum airway suction pressure preceding arousal was significantly higher on E nights. Conversely, the rate of increase in inspiratory effort (maximum pressure) during occlusion was decreased by E. We conclude that moderate ethanol ingestion prolongs the time to arousal following airway occlusion by increasing the threshold of inspiratory effort associated with arousal and by decreasing the rate of increase in the magnitude of inspiratory efforts. PMID- 1736756 TI - Adenosine stimulation, ventilation, and arousal from sleep. AB - The mechanism for arousal from sleep resulting from respiratory stimuli is unclear. We hypothesized that arousal is a result of increasing ventilation during sleep. To determine if this is true we compared minute ventilation at the point of arousal from non-REM sleep produced by the respiratory stimulant adenosine to that resulting from progressive hypercapnic stimulation. If this hypothesis is correct, the quantity of breathing immediately preceding arousal from sleep should be similar for each stimulus. We monitored electroencephalogram (EEG), electromyogram (EMG), end-tidal CO2, and inspired minute ventilation (VI) in five healthy young men during full-night sleep studies. Sleep state was monitored during the baseline state, during an intravenous infusion of 80 micrograms/kg/min of adenosine, and during multiple trials of progressive hyperoxic hypercapnia. Arousal from sleep occurred in association with increased breathing 4.2 +/- 1.1 times during adenosine infusion, 2.0 +/- 0 times during hypercapnic stimulation, and 4.0 +/- 0.6 times in the absence of stimulated breathing (spontaneously) per subject. Minute ventilation for the breath preceding arousal associated with adenosine stimulation (13.0 +/- 1.4 L/min) was similar to that preceding arousal caused by hypercapnia (12.9 +/- 1.1 L/min). In each case this level of breathing was greater than that preceding spontaneously occurring arousals (8.2 +/- 1.1 L/min), p less than 0.05). Although variable between subjects, there was a high correlation for these two variables within subjects (R = 0.96, p = 0.01). These data support the hypothesis that increasing ventilation induces arousal from sleep when ventilation is increased regardless of the stimulus producing this rising drive to breathe. PMID- 1736757 TI - Detection of inspiratory resistive loads by heart-lung transplant recipients. AB - Human heart-lung transplantation recipients (HL) are models for the effects of selective lower respiratory tract denervation. We used a series resistor to examine thresholds of inspiratory flow resistance perception among 16 HL in comparison with 15 normal control subjects (C) and 12 heart transplant recipients (H). HL and C were closely age matched. H subjects were older and had mildly reduced lung volumes compared with the other groups. The perception threshold was defined as the added resistance (delta R) detected by subjects at 50% of random, blinded presentations. These delta R were subsequently expressed as a fraction of the airway resistance of the subject and baseline resistance of the apparatus (delta R/Raw + Rapparatus), otherwise known as the Weber fraction. The mean +/- SEM Weber fractions were nearly identical for HL and C (0.32 +/- 0.05 versus 0.34 +/- 0.05, respectively). The Weber fraction of H (0.74 +/- 0.17) was significantly greater than those of both other groups (p less than 0.05 by Kruskal-Wallis test). We conclude that lower respiratory tract afferents do not play a significant role in the perception of inspiratory resistive loads. The finding of an abnormally high Weber fraction in the heart transplant population remains unexplained but may be a function of age or restrictive pulmonary defects. PMID- 1736758 TI - Relationship of respiratory effort sensation to expiratory muscle fatigue during expiratory threshold loading. AB - We investigated whether fatigue of the expiratory muscle, that is, the abdominal muscle, may account for a change in the respiratory effort sensation in normal subjects during expiratory threshold loading. The respiratory effort sensation was scored using a modified Borg scale. Expiratory muscle fatigue was assessed both from changes in the maximal static expiratory pressure and in the centroid frequency (fc) of the abdominal muscle electromyogram (EMG). Expiratory threshold loading (magnitude of threshold; 40 to 60% of the maximal expiratory pressure at FRC, breathing frequency = 15/min, and duty cycle = 0.5) was continued until exhaustion or for 30 min. Loading was repeated following a 15-min recovery period after the end of the first expiratory loading. The maximal static expiratory pressure during loading (Pmmax) decreased initially and then remained decreased. Decreases were smaller with the 40% load (22 +/- 6%, SEM) than with the 60% load (37 +/- 3%) (p less than 0.05). The decrease during the second run of the 60% load was greater than during the first (p less than 0.01 by ANOVA). The maximal expiratory pressure at TLC before the second run of the 60% load was decreased by 9 +/- 3% compared with the control (p less than 0.02) but that with the 40% load was not. The fc with the 60% load decreased initially by 8 +/- 1% and then remained constant, although no change was observed with the 40% load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736759 TI - A factor analysis of dyspnea ratings, respiratory muscle strength, and lung function in patients with chronic obstructive pulmonary disease. AB - The purpose of this study was to demonstrate that clinical ratings of dyspnea and physiologic function are separate dimensions underlying the pathophysiology of chronic obstructive pulmonary disease (COPD). We used principal-components factor analysis to confirm these dimensions using data collected prospectively in 86 symptomatic patients with COPD. Three different instruments were used to rate dyspnea: a modified Medical Research Council (MRC) scale, the oxygen cost diagram (OCD), and the baseline dyspnea index (BDI). Measures of physiologic function included standard spirometric measures (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) and maximal inspiratory (PImax) and expiratory (PEmax) mouth pressures. Age of the 65 male and 21 female subjects was 62.9 +/- 1.2 yr (mean +/- SEM). All three clinical scales were significantly correlated with physiologic function (range of r values, 0.32 to 0.45; p less than 0.05), except for the relationship between the MRC scale and PEmax (r = 0.14; p = NS). The factor analysis yielded three factors that accounted for 71.9% of the total variance of the data: clinical ratings of dyspnea (MRC scale, OCD, and BDI) loaded on the first factor; maximal respiratory pressures and gender loaded on the second factor; and lung function and age loaded on the third factor. Additional post hoc factor analysis provided similar results when the sample was divided into two subgroups by randomization, by severity of dyspnea ratings, or by severity of airflow obstruction. We conclude that dyspnea ratings, maximal respiratory pressures, and lung function are separate factors or quantities that independently characterize the condition of patients with COPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736760 TI - Group B streptococcus has no effect on piglet diaphragmatic force generation. AB - Recent studies indicate that diaphragmatic contractility is adversely affected by bacterial infection. Using transdiaphragmatic pressure (Pdi) with phrenic nerve stimulation, the effect of continuous Group B Streptococcus (GBS) infusion on diaphragmatic force output was studied in seven anesthetized, spontaneously breathing 1-month old piglets. Pdi was measured under baseline condition (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. The GBS was infused at a level that caused a doubling of the pulmonary artery pressure and a 32% decrease in cardiac output but which avoided hypotension or acidosis--both of which can decrease diaphragmatic contractility. In addition, the piglets were kept hyperoxic (PaO2 greater than 100) and no piglet with hypercapnia (PaCO2 greater than 65) was studied, as hypoxia and hypercapnia also can cause respiratory muscle dysfunction. Pdi in response to phrenic nerve stimulation did not change during GBS infusion. We conclude that GBS infusion, in the absence of hypotension, hypercapnia, hypoxia, or acidosis, has no effect on diaphragmatic force generation in the piglet. PMID- 1736761 TI - The impact of grain dust on respiratory health. PMID- 1736762 TI - Evaluation of a new method for assessing arterial oxygen pressure, avoiding arterial blood collection. AB - Arterial computed PO2 (PO2 com) was computed from SaO2 ear and finger capillary pH using equations of Severinghaus and Ellis, and compared with measured arterial PaO2 in 100 patients with chronic obstructive pulmonary disease (76 men, aged 42 to 82 yr). SaO2 ear ranged from 73 to 98%. There was no significant difference between SaO2 ear and SaO2 com (calculated from PaO2 and arterial pH), nor between arterial pH and pHc (capillary blood). Mean directly measured finger capillary oxygen tension, PcO2, was lower than PaO2 by 10.1 mm Hg +/- 5.4 SD. Mean bias of (PaO2-PO2 com) was -0.22 mm Hg +/- 2.6 SD. When subdivided by range, bias, and SD of mean bias of (PaO2-PO2 com) were -0.47 mm Hg +/- 2.5 with SaO2 ear less than 95% and 0.1 mm Hg +/- 2.9 with SaO2 ear greater than 95%. We conclude that PaO2 may be reliably computed from SaO2 ear and capillary pH when SaO2 ear is less than 98%. PMID- 1736763 TI - Direct effects on airway smooth muscle contractile response caused by endothelin 1 in guinea pig trachealis. AB - Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, causes tracheal smooth muscle (TSM) relaxation followed by sustained contraction when administered intravenously in guinea pigs by a mechanism that depends upon an intact airway epithelium. To elucidate the potential role of the epithelium in modulating the response to ET-1 and the potential effects of local release of ET 1, we studied the effects of topical application of ET-1 to a segment of TSM in situ. An epithelium smooth muscle preparation that does not disrupt normal anatomic relationships was used; smooth muscle contraction was measured isometrically in vivo. Application of 10(-10) mol/cm2 ET-1 to the epithelial surface in six animals caused 2.27 +/- 0.45 g/cm active tension (AT) of the TSM segment after 30 min (p less than 0.05 versus baseline); an initial relaxation response was not observed. Endothelin-1 was dose-dependent and was 1,000 times more potent than acetylcholine in causing AT in TSM. Pretreatment with ET-1 did not alter the subsequent response to acetylcholine. Contraction elicited by topical application of ET-1 persisted greater than 3 h. In five animals in which the epithelium was removed, 10(-10) mol/cm2 ET-1 caused 4.45 +/- 0.92 g/cm AT after 30 min (p less than 0.05 versus intact epithelium). These data suggest that topical application of ET-1 elicits responses that are different from those elicited in the same preparation after intravenously administered ET-1: (1) TSM contraction that is not preceded by a transient relaxation phase, and (2) contraction that is not reduced after removal of the epithelium. PMID- 1736764 TI - Isoniazid-associated hepatitis deaths: a review of available information. PMID- 1736765 TI - Assessing precision and accuracy in blood gas proficiency testing. PMID- 1736766 TI - Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. AB - OBJECTIVE: To assess whether daily ingestion of yogurt containing Lactobacillus acidophilus prevents vulvovaginal candidal infections. DESIGN: Crossover trial for at least 1 year during which patients were examined for candidal infections and colonizations while receiving either a yogurt-free or a yogurt-containing diet. Patients served as their own controls. SETTING: Ambulatory infectious disease center in a teaching hospital providing tertiary care. PATIENTS: Thirty three women with recurrent candidal vaginitis were eligible after recruitment from community practices and clinics and through advertising. Twelve patients were eliminated for protocol violations. Of the remaining 21 patients, 8 who were assigned to the yogurt arm initially refused to enter the control phase 6 months later. Thus, 13 patients completed the protocol. INTERVENTIONS: Women ate yogurt for 6 months of the study period. MEASUREMENTS: Colonization of lactobacilli and candida in the vagina and rectum; candidal infections of the vagina. MAIN RESULTS: Thirty-three eligible patients were studied. A threefold decrease in infections was seen when patients consumed yogurt containing Lactobacillus acidophilus. The mean (+/- SD) number of infections per 6 months was 2.54 +/- 1.66 in the control arm and 0.38 +/- 0.51 per 6 months in the yogurt arm (P = 0.001). Candidal colonization decreased from a mean of 3.23 +/- 2.17 per 6 months in the control arm to 0.84 +/- 0.90 per 6 months in the yogurt arm (P = 0.001). CONCLUSION: Daily ingestion of 8 ounces of yogurt containing Lactobacillus acidophilus decreased both candidal colonization and infection. PMID- 1736767 TI - Evaluation of syncope by upright tilt testing with isoproterenol. A nonspecific test. AB - OBJECTIVE: To determine the proportion of patients with syncope of unknown etiology who have a positive response to upright tilt testing and to determine the specificity of this test as a marker for vasodepressor syncope. DESIGN: Comparison of upright tilt testing with isoproterenol in patients with syncope of unknown etiology and in controls. SETTING: Outpatient clinics of a tertiary care center. PATIENTS: A total of 20 patients with syncope of unknown etiology and 40 controls matched by age, sex, and lack of underlying cardiovascular or other diseases had upright tilt testing with isoproterenol infusion. Controls consisted of two groups (groups I and II) who had slightly different methods of tilt testing in conjunction with isoproterenol. INTERVENTIONS: Upright tilt testing at 80 degrees from horizontal was done for up to 15 minutes. If end points were not reached, infusion of isoproterenol was started at 1 microgram/min and increased with graded increments in infusion rates up to 5 micrograms/min. MEASUREMENTS: The development of syncope or presyncope in association with hypotension, bradycardia, or both. MAIN RESULTS: Positive response to tilt testing in patients with syncope was 75% (95% CI, 55% to 95%); it was 65% in control group I (CK, 44% to 86%) and 45% in control group II (CI, 20% to 70%). Case patients and controls with positive tilt-test responses were similar with respect to time to completion of the test, mean total isoproterenol dose, mean isoproterenol dose level at completion, average mean blood pressure at completion, mean heart rate at completion, mean decline in systolic blood pressure, and decline in mean blood pressure or heart rate (P greater than 0.05 for all comparisons). Further, symptoms during tilt testing in case patients with positive responses were similar to those in controls with positive tilt-test results. CONCLUSIONS: The rate of positive tilt testing in patients with syncope is equivalent to that in controls without a history of syncope. The low specificity of this test makes its use as a marker for vasodepressor syncope questionable. PMID- 1736768 TI - Treating sickle cell pain like cancer pain. AB - OBJECTIVE: To assess the effect of a structured analgesic regimen on hospital use by patients with sickle cell disease. INTERVENTION: Intravenous and oral controlled-release morphine was used instead of intramuscular meperidine and short-acting oral opioids for the treatment of sickle cell pain. DESIGN: Time series in which emergency and admission records for four 6-month periods before and two 6-month periods after the institution of the new analgesic protocol were reviewed. SETTING: Inner-city university hospital providing care for adults with sickle cell disease. PATIENTS: All patients (an average of 50) who used the emergency department of the inpatient medical service for treatment of sickle cell crisis during the study periods. MEASUREMENTS AND MAIN RESULTS: The number of admissions for sickle cell pain decreased by 44%, total inpatient days by 57%, length of hospital stay by 23%, and the number of emergency department visits by 67% after initiation of the morphine protocol. Hospital use remained at these lower levels one year later. Similar declines were seen for a subset of 15 patients who had a history of frequent admissions for sickle cell pain and who used this hospital exclusively and accounted for more than half of the admissions for sickle cell disease. CONCLUSIONS: A pain-control program modeled on regimens used to treat chronic cancer pain reduced hospital use by adult patients with sickle cell pain. PMID- 1736769 TI - Mechanical restraint use and fall-related injuries among residents of skilled nursing facilities. AB - OBJECTIVE: To evaluate the association between mechanical restraint use and the occurrence of injurious falls among persons residing in skilled nursing facilities. DESIGN: Prospective observational cohort study. SETTING: Twelve skilled nursing facilities in southern Connecticut. PARTICIPANTS: The 397 persons who were mobile and unrestrained at baseline. MEASUREMENTS: Restraint use was defined both as the number of days restrained and as "never," "intermittently," or "continually" restrained. The primary outcome measure was the occurrence of a serious fall-related injury. Analyses were done on the entire cohort as well as on a subgroup hypothesized as having a high risk for falls. MAIN RESULTS: During one year of follow-up, 122 subjects (31%) became restrained, 83 intermittently and 39 continually. A serious fall-related injury was experienced by 5% (15 of 275) of unrestrained, compared with 17% (21 of 122) of restrained, subjects (chi square = 12.478; P less than 0.001). Restraint use remained independently associated with serious injury after adjusting for other factors, both in the entire cohort (adjusted odds ratio, 10.2; 95% CI, 2.8 to 36.9) and in the high risk subgroup (adjusted odds ratio, 6.2; CI, 1.7 to 22.2). Among the 305 subjects who experienced two or fewer falls, the proportion having a serious injury was 15% for restrained subjects compared with 4% for unrestrained subjects (difference in proportions 11%, CI, 4% to 17%), whereas the comparable proportions for the 92 subjects who experienced more than two falls were 20% and 16%, respectively. Results were similar in the high-risk subgroup. CONCLUSIONS: Mechanical restraints were associated with continued, and perhaps increased, occurrence of serious fall-related injuries after controlling for other injury risk factors. Study results suggest the need to consider whether restraints provide adequate, if any, protection. PMID- 1736770 TI - Efficacy and risks of moricizine in inducible sustained ventricular tachycardia. AB - OBJECTIVE: To assess the efficacy and toxicity of moricizine in treating patients with serious ventricular arrhythmias and inducible sustained ventricular tachycardia. DESIGN: Uncontrolled clinical trial. SETTING: The intensive care and telemetry units of Northwestern Memorial Hospital, St. Francis Hospital and Medical Center, and Lenox Hill Hospital. PATIENTS: Twenty-six patients with sustained ventricular arrhythmias or hemodynamically significant nonsustained ventricular tachycardia, most of whom failed therapy with at least one class I antiarrhythmic agent. INTERVENTION: Patients were treated with moricizine, 400 to 1000 mg/d. MEASUREMENT: Efficacy was assessed by the results of programmed ventricular stimulation done during moricizine therapy. MAIN RESULTS: Seven of the 26 patients (27%) developed life-threatening ventricular proarrhythmia during moricizine loading. Three patients had incessant sustained ventricular tachycardia, two had incessant nonsustained ventricular tachycardia, one had new sustained ventricular tachycardia, and one had new cardiac arrest. One of these patients died of intractable ventricular fibrillation. No clinical or electrophysiologic variables clearly identified those at risk for proarrhythmia. Only 3 of 26 patients (12%) became noninducible on moricizine. CONCLUSION: Moricizine has a low rate of efficacy and carries a considerable risk for life threatening proarrhythmia in patients with serious ventricular arrhythmias and inducible ventricular tachycardia who have failed therapy with other class I antiarrhythmic agents. PMID- 1736771 TI - Electrophysiologic response to moricizine in patients with sustained ventricular arrhythmias. AB - OBJECTIVE: To assess the short-term efficacy and safety of moricizine in patients receiving electrophysiologically guided therapy for sustained ventricular arrhythmias refractory to treatment with class IA antiarrhythmic agents. DESIGN: Uncontrolled clinical trial. SETTING: Referral-based teaching medical center. PATIENTS: Twenty-one patients (18 of whom had coronary artery disease) with a mean left ventricular ejection fraction of 32% +/- 11% who presented with sustained ventricular tachycardia (13 patients), syncope (4 patients), or cardiac arrest (4 patients). INTERVENTIONS: Moricizine, 743 +/- 85 mg daily. MEASUREMENTS: Electrophysiologic testing in the drug-free state and after administration of moricizine unless sustained arrhythmias occurred. MAIN RESULTS: Sustained ventricular tachycardia was inducible in the absence of antiarrhythmic drugs in 20 patients and was not suppressed by moricizine in any patient. Four patients had six episodes of spontaneous ventricular tachycardia while receiving moricizine. A probable proarrhythmic response occurred in four patients. CONCLUSION: In patients with compromised left ventricular function caused by coronary artery disease in whom class IA antiarrhythmics were ineffective, moricizine was ineffective in suppressing sustained ventricular arrhythmias and resulted in proarrhythmic effects in some patients. PMID- 1736772 TI - Graft-versus-host disease in a liver transplant recipient. PMID- 1736773 TI - Prudent strategies for elective red blood cell transfusion. AB - OBJECTIVE: To review the literature on the appropriateness of red blood cell transfusion and current physician practice, with emphasis on the physiologic and symptomatic implications of elective transfusion in the treatment of anemia. DATA SOURCES: Studies on the therapeutic use of red blood cell transfusion were identified through a search of MEDLINE (1966 to the present) and through a manual review of bibliographies of identified articles. In addition, evidence was solicited from selected experts in the field and recent consensus panels that have developed transfusion guidelines. DATA SYNTHESIS: No controlled trials of blood transfusion were identified, but data were available on four issues relevant to transfusion practice: current physician practice and evidence for excessive use of red blood cell transfusion; physiologic adaptation to anemia; human tolerance of low hemoglobin levels; and strategies for reducing homologous transfusion requirements. CONCLUSIONS: Despite the recent decline in red blood cell use because of concerns about infection, current transfusion practice remains variable because physicians have disparate views about its appropriateness. The remarkable human tolerance of anemia suggests that clinicians can accept hemoglobin levels above 70 g/L (7 g/dL) in most patients with self-limited anemia. In patients with impaired cardiovascular status or with anemias that will not resolve spontaneously, however, the data are insufficient to determine minimum acceptable hemoglobin levels, and therapy must be guided by the clinical situation. Several therapeutic strategies and pharmacologic interventions are available in the perioperative and non-operative settings to further reduce red blood cell use. PMID- 1736774 TI - The corporate organization of hospital work: balancing professional and administrative responsibilities. AB - The development of the hospital into a corporation has influenced the care of patients and the work of the professional staff. As a corporate enterprise, the modern hospital has a private agenda aimed at increasing growth and efficiency with an emphasis on technical services, professionals as employees, and patients as customers. These changes have resulted in a decrease in trustee and professional authority and an increase in administrative control. This shift in the control structure has continued in response to the need for accounting and regulation of services and in response to demands for increased growth and efficiency made by an increasingly competitive market environment. Strategies for the reorganization of hospital staff aimed at improving both inpatient and outpatient care are reviewed. The reorganization of the institution and staff, using either a staff group-practice corporation or an administrative staff model, is proposed. Clinicians have new responsibilities for developing collective arrangements for institutional governance, for allocating institutional resources, for providing public accountability regarding the use of these resources, and for defining the missions of care. PMID- 1736775 TI - Enriching the doctor-patient relationship by inviting the patient's perspective. AB - Doctors and patients alike are saddened and angered by the distance that increasingly interferes with their interactions. Two complementary strategies may enhance the human quality of clinical care and improve outcomes. First, the doctor and patient can undertake a systematic "patient's review" that addresses seven dimensions of care: 1) respect for patient's values, preferences, and expressed needs; 2) communication and education; 3) coordination and integration of care; 4) physical comfort; 5) emotional support and alleviation of fears and anxieties; 6) involvement of family and friends; and 7) continuity and transition. Incorporating the "review" into the clinical encounter encourages both patient and doctor to confront individual preferences and values and offers patients an explicit framework for participating actively in their care. Second, using survey instruments designed to solicit focused reports from patients that address each dimension of care, doctors can gather aggregate feedback about their practices. Such reports move beyond anecdote and can serve as screening tests that uncover areas in doctors' practices that merit improvement. In addition, patients can join doctors in developing solutions to problems uncovered by patients' reports. PMID- 1736776 TI - Lactobacillus prophylaxis for Candida vaginitis. PMID- 1736777 TI - An invitation to join a controversy. PMID- 1736778 TI - The nicotine transdermal patch: a cautionary note. PMID- 1736779 TI - Wilson disease--penicillamine therapy and late presentation. PMID- 1736780 TI - Wilson disease--penicillamine therapy and late presentation. PMID- 1736781 TI - Serum cholesterol as a prognostic factor after myocardial infarction. PMID- 1736782 TI - Reversal of the nephrotic syndrome by colchicine in amyloidosis of familial Mediterranean fever. PMID- 1736783 TI - Rheumatoid arthritis-like disease after alpha-interferon therapy. PMID- 1736784 TI - Mortality rate of community-acquired pneumonia: 1944 and today. PMID- 1736785 TI - Hepatitis B--an occupational risk for butchers? PMID- 1736786 TI - Testing remedies for the shortage of organs. PMID- 1736787 TI - "A poisoned tooth". PMID- 1736788 TI - Intraoperative parathyroid hormone estimation: a valuable adjunct to parathyroid surgery. AB - Serial measurements of serum intact parathyroid hormone (PTH) and adjusted total calcium levels were performed on 10 patients during unilateral neck exploration for a solitary parathyroid adenoma localised preoperatively by ultrasound scan. Frozen section was performed peroperatively to establish the presence of parathyroid tissue. Levels of PTH were shown to be within the normal range within 15 min of adenoma removal (a mean of 13.4% of their preoperative values), allowing clear early distinction from unsuccessful surgery where no change occurred. Frozen section wrongly identified thyroid tissue as parathyroid in one case leading to a failure of the initial neck exploration. Our findings show that intraoperative PTH measurements can accurately predict whether all hyperfunctioning parathyroid tissue has been removed. This is not always possible using frozen section techniques. The wider use of intraoperative PTH measurement, particularly in difficult cases, may avoid the need for prolonged explorations to identify all four glands and, perhaps, biopsy of normal glands, replacing the current standard use of frozen section as a more reliable indicator of the success of parathyroid surgery. PMID- 1736789 TI - Paraoesophageal hiatus hernia: surgery for all ages. AB - The results of surgery for paraoesophageal hiatus hernia over a 10-year period have been studied. From a group of 26 symptomatic patients, elective repair has been undertaken in 20 (mean age of 65.6 years) and emergency repair in four (mean age of 73.1 years). Emergency surgery was associated with a fivefold increase in mortality, and anatomical repair gave a satisfactory result in 90% (CI 77-100) of survivors. Surgical treatment should be considered for all symptomatic patients with paraoesophageal hiatus hernia. PMID- 1736790 TI - Contamination of underwater seal drainage systems in thoracic surgery. AB - The incidence of bacteriological contamination of drainage fluid (water constituting the underwater seal plus drainage effluent) was studied in 38 patients (50 chest drains), up to 6 days after thoracotomy. No bacteriological contamination was demonstrated in any of the samples taken during this period of time. We conclude that the underwater seal drainage system may be left for up to 6 days postoperatively without change of any of its components and without risk of contamination. PMID- 1736791 TI - Management of synchronous arterial occlusions using intra-arterial thrombolysis. AB - Three patients presented with multiple acute arterial occlusions in separate limb vessels. The diagnosis was confirmed by angiography. Each patient was successfully treated by simultaneous infusion of low-dose intra-arterial streptokinase into each occlusion. All of the patients were improved clinically and in two patients completely normal pressure indices were restored. PMID- 1736792 TI - Unsuccessful outpatient counselling to help patients with peripheral vascular disease to stop smoking. PMID- 1736793 TI - Injury to the superior mesenteric artery during pancreatectomy for chronic pancreatitis. AB - Four cases are described of injury to the superior mesenteric artery (SMA) during pancreatectomy for chronic pancreatitis. Review of the literature indicates that this is a rare event. In three patients (arterial ligation, 2; haemorrhage, 1), the injury was immediately recognised and successfully repaired. In the fourth (with probable occlusion of the vessel), the problem was not appreciated at operation and the patient eventually died. Vessels adherent to a pseudocyst are at particular risk of injury, as in two of our patients. Two patients had ectopic origin of the right hepatic artery. Since awareness of such vascular anomalies is important, we now perform selective mesenteric angiography in all patients requiring pancreatic resections, whether proximal or distal. PMID- 1736794 TI - How does computer-aided diagnosis improve the management of acute abdominal pain? AB - The introduction of standardised data-collection forms and computer-aided diagnosis has been found to be associated with improved diagnosis and management of patients with acute abdominal pain. The mechanism by which such benefits accrue has been the subject of some controversy. Detailed analysis of 5193 patients from one hospital shows that the major benefit from such diagnostic aids was the accurate early diagnosis of non-specific abdominal pain by senior house officers in the accident and emergency department; this in turn led to fewer admissions and fewer operations with negative findings. Clinical data about patients with acute abdominal pain should be recorded on structured information sheets by junior doctors and early positive diagnosis should be encouraged before decisions affecting the patient's management are made. Improved computer support may confer further benefits. PMID- 1736795 TI - Combined surgical audit by microcomputer involving units in four health regions. AB - General surgeons from hospitals in four well-separated health districts collected audit data about their patients using common software. They pooled their results in order to make comparisons between their practices. Data on 22,497 admissions including 17,473 operations were available. The data were found to be easy to collect and analyse using this program. There were significant differences in overall complication rates between the four centres, but these seem to be explained by differences in the emergency workload, case mix, and age range of the population treated. A study of inguinal hernia repairs and appendectomies showed low complication rates with no significant differences between centres, with the single exception of a higher incidence of wound problems in one centre. Because of the multiplicity of factors affecting them, complication rates could only be properly understood in a professional surgical context. Isolated figures would be open to damaging misrepresentation. Meetings between surgeons well armed with their own results seem to be the best way to forward the audit process. PMID- 1736796 TI - Prevention of occupational transmission of HIV in the ENT clinic. AB - Much attention has been focused on the risks of inoculation with the human immune deficiency virus in the operating theatre. However, less emphasis has been placed on infection resulting from outpatient exposure to this pathogen. A survey of current protective measures undertaken by ENT consultants in the outpatient clinic in the United Kingdom is presented. The precautions employed by the majority of these subjects are inadequate and non-universal. A review of the risk factors and subsequent safety recommendations is detailed. PMID- 1736797 TI - Blood transfusion: an overused resource in colorectal cancer surgery. AB - The use of blood transfusion was examined in 476 patients who underwent curative surgery for large bowel cancer. Of these patients, 128 were not transfused while 348 received a total of 1174 units of blood. A patient was considered over transfused if the predischarge haemoglobin was more than 12 g/dl. Using this criteria and accepting that single unit transfusions should be avoided, transfusion could have been avoided in 30% of the patients and a total of 377 units were given unnecessarily. Major under-transfusion did not occur; no patient being discharged with a haemoglobin of less than 9 g/dl. This study shows that blood transfusion is overused and the reasons for its use rarely recorded. In view of the morbidity related to transfusion, it is suggested that surgeons and anaesthetists reappraise their transfusion policy and the first step in this must be to record the reason for transfusion. PMID- 1736798 TI - Surgical excision alone is adequate treatment for primary colorectal cancer. AB - This debate examines the arguments for and against the proposal that surgical excision alone is adequate treatment for primary colorectal cancer. The arguments in favour are that the results from curative surgery are excellent and that despite many trials of adjuvant chemotherapy, radiotherapy and immunotherapy, the proposed benefits remain unproven. Recent improvements in surgical technique, particularly for dissection of rectal tumours, have shown the way towards further improvement using surgery alone, and it is clear from a national survey that technical factors related to individual surgeons play a large part in determining recurrence rates. With optimum primary treatment, surgical excision alone is indeed adequate therapy. The arguments against this motion are that although a considerable number of patients do survive with surgery, the 5-year survival rate is poor when there is extensive local invasion or lymphatic metastases. Surgery starts therapy by reducing the tumour load, but other modalities are required to destroy the cells which might subsequently develop into metastases. Trial results with adjuvant therapy are encouraging, although many contain too few patients. We cannot be content with the results of treatment of Dukes' Stage B and C tumours; more trials are needed to determine the best treatment for these patients. PMID- 1736799 TI - Portoenterostomy scissors: a new instrument for surgery in the porta hepatis. AB - A new design of scissors is described which has been found to be extremely useful during dissection of the porta hepatis. In particular its use is recommended for the portoenterostomy procedure of infancy (Kasai's operation). PMID- 1736800 TI - Simulated laparoscopic cholecystectomy. AB - A new simulator specifically designed for practising techniques in laparoscopic cholecystectomy is described. The simulator is inexpensive and utilises pig gallbladders. It allows a surgeon to practice without the need for assistance. PMID- 1736801 TI - Cetrimide lavage: ineffective and potentially toxic. PMID- 1736802 TI - A controlled trial of short-term versus standard axillary drainage after axillary clearance and iridium implant treatment of early breast cancer. PMID- 1736803 TI - Pulse oximetry in closed limb fractures. PMID- 1736804 TI - Assessment of burn injury in the accident and emergency department: a review of 100 referrals to a regional burns unit. PMID- 1736805 TI - CA15-3: a reliable indicator of metastatic bone disease in breast cancer patients. AB - Carcinoma of the breast is the most common malignancy in women and is frequently associated with metastatic bone disease and its associated osteolytic morbidity and mortality. Traditional radiological methods for mass screening bony secondaries are not cost-effective. We examined the value of the tumour marker 'CA15-3' as an alternative to conventional isotope bone scintigraphy. A total of 218 patients with breast cancer was evaluated over a 4-year period. Venous CA15-3 levels were obtained at 3-monthly intervals and bone scintigraphy annually or if the patient developed locomotor symptoms or exhibited elevated CA15-3 levels. Of these patients, 33 with metastatic breast carcinoma had an elevated tumour marker level at the time of diagnosis of their metastases; bone metastases alone = 15/17 (88%), soft tissue metastases alone = 2/6 (33%), simultaneous bony and soft tissue metastases = 7/10 (70%). The preponderance of an elevated CA15-3 in metastatic bone disease, be it in isolation or in combination with non-bone metastases, yields a sensitivity, specificity and positive predictive value of 81.5%, 66% and 92%, respectively. Although 22 of the 27 patients had an elevated CA15-3 at the time of diagnosis of their bone metastases, the remaining five patients (with tumour marker levels in the normal range) showed a similar, albeit a delayed, increase (median = 3 months). Thus, all metastatic bone disease patients demonstrated elevated marker levels. We recommend CA15-3 as a simple, reliable and inexpensive screening method for detecting bone metastases in the patient with breast carcinoma. PMID- 1736806 TI - Measuring change in surgical practice. AB - We reviewed the work of a single general surgical firm over six years--about 11,500 patient episodes. Although the workload remained approximately constant, a severe reduction in the number of available beds was accompanied by a marked change towards shorter duration of stay. This affected particularly the elective cases. Previous authors, when trying to predict requirement of hospital beds, have accepted that duration of stay and number of beds available are independent variables; this was not what we observed. PMID- 1736807 TI - A weekend orthopaedic initiative list scheme. AB - The feasibility and safety of running an elective orthopaedic service at the weekend is demonstrated. Weekend timing of such surgery appears to be very popular with patients. The cost of not assessing patients pre-operatively in terms of theatre time lost is shown. PMID- 1736808 TI - A guide to the use of electronic bulletin boards. AB - Data transfer between distant computers is potentially a rapid and efficient method of gathering and disseminating information. Bulletin Boards can coordinate this activity but their benefit is proportional to the number of users. The initial telephonic connection between computers and the subsequent data transfer is complex; this review attempts to explain some of the theory and problems involved. PMID- 1736809 TI - Further studies with short duration ribavirin aerosol for the treatment of influenza virus infection in mice and respiratory syncytial virus infection in cotton rats. AB - Ribavirin aerosol administration has been shown to be effective in the treatment of respiratory syncytial virus (RSV) infections in infants and in influenza A and B virus infections in young adults. Long treatment schedules and potential for environmental contamination have stimulated the search for alternative dosing schedules. Thus, we attempted to determine the length of time of ribavirin aerosol necessary for effective treatment of influenza and RSV. In RSV-infected cotton rats, aerosolization for just 30 min with high-dose ribavirin (HDR:60 mg ribavirin/ml in reservoir), 3 times daily, reduced viral lung titers/gm of tissue by 1.1 log10. In influenza virus-infected mice, 15 min of aerosolized HDR, 3 times daily, was effective in reducing both mortality and pulmonary virus titers (1.1 log10 reduction). When the intervals between aerosol administration each day were equally divided (i.e., q.8 h), the treatments were most effective. Treatment for 45 min, once daily, was not as effective as divided doses. Calculations of ribavirin concentrations in respiratory secretions following 15 min treatment in mice with HDR indicated that drug levels dropped below the ED50 for influenza viruses after about 9 h. A daily dosage of ribavirin, estimated to be 8-15 mg/kg, was effective for the treatment of influenza and RSV infections. PMID- 1736810 TI - A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1. AB - Sequences from the gag, pol and rev regions of the RF strain of HIV-1 (HIV-1RF) were chosen as targets for antisense phosphorothioate oligodeoxynucleotides (S oligos). These sequences were the p18/p24 junction in gag, the active site of HIV protease in pol; a sequence from the first exon of the rev gene and S oligodeoxycytidylic acid controls. Compounds were tested against HIV-1 in both acutely and chronically infected cells. The results show that these phosphorothioate analogues tested in acutely infected cells were active in the 0.1-2 microM range, were dependent on chain length but had no sequence specificity. To study the mechanism of action, the time of addition of S-oligos to acutely infected cells was delayed for up to 48 h post-infection. It was found that antiviral activity was lost when compounds were added to the cultures later than 10 h post-infection. With chronically infected cells only the antisense rev sequence showed activity at 30 microM and neither of the gag or pol antisense sequences has a significant effect on HIV replication at 50 microM. These results are consistent with previous in vitro studies which demonstrate that antisense S oligodeoxynucleotides have several modes of action. PMID- 1736811 TI - Comment on the paper: A three-dimensional model to analyze drug-drug interactions. Prichard, M.N. and Shipman, C., Jr. (1990) Antiviral Res. 14, 181 206. PMID- 1736812 TI - Practice models for perioperative nursing, effectiveness initiative being explored by Project Teams. PMID- 1736813 TI - Intraoperative echocardiography. An essential tool in cardiac surgery. PMID- 1736814 TI - Arterial blood gas interpretation. Improving perioperative skills. PMID- 1736815 TI - Reducing blood contamination and injury in the OR. A study of the effectiveness of protective garments and OR procedures. PMID- 1736816 TI - From thesis to publication. Preparing your school paper for publication. PMID- 1736817 TI - Position statement on the role of the RN in the management of patients receiving i.v. conscious sedation for short-term therapeutic, diagnostic, or surgical procedures. PMID- 1736818 TI - Position statement on the role of the RN in the management of analgesia by catheter techniques (epidural, intrathecal, intrapleural, or peripheral nerve catheters). PMID- 1736819 TI - AORN quality improvement standards for perioperative nursing. PMID- 1736820 TI - Proposed recommended practice. Steam and ethylene oxide (EO) sterilization. PMID- 1736821 TI - AIDS and nursing. Attitudes and knowledge of AIDS affect comfort in providing care. PMID- 1736822 TI - Passing surgical instruments, sharps without injury. PMID- 1736823 TI - Advance directives and the Patient Self-Determination Act. PMID- 1736824 TI - Injectable local anesthetics. PMID- 1736825 TI - Annotated tray lists save time, decrease errors. AB - We have achieved more consistency in instrument processing by using the annotated tray lists. This improved consistency has resulted in fewer errors and damaged instruments. Important tasks, such as lubricating the instruments, are not being overlooked inadvertently or performed incorrectly by staff. Productivity has increased because information is available when questions arise. Technicians do not have to look through large procedure manuals or ask other technicians to identify instruments and perform specific procedures. While the tray lists do not replace formal procedure manuals, they are helpful adjuncts for personnel who prepare the surgical trays. PMID- 1736826 TI - AORN revised statement on the patient and health care workers with human immunodeficiency virus (HIV) and other bloodborne diseases. PMID- 1736827 TI - [What is the role of statistics in medical science?--a critical essay]. AB - In the present paper, the fundamental problems of statistics used in medical science are discussed, based on radical criticism and thorough examination of statistical ideas and methods which are popularly used in the medical field of today. The formal applications of statistical test and estimation theories in mathematical statistics and further belief in double-blind experimental design are frequently found in medical science, where the meaning of population is not made clear and the true characteristics of "statistical test and estimation" and of "double-blind experimental design" are either not understood or are misunderstood. These facts bring many evil influences on medical ideas leading to medical trials. Radical criticism and thorough examination are necessary for the return of medical research to the right path. New statistical ideas and methods must be developed on the basis of the considerations mentioned above. The use of statistics must be made with a modest attitude and exploratory or detective ideas must be adopted, in so far as medical trials are administered, with human mind, to individuals who are intricate and multifarions in reaction. Medical trials and statistics are to be unified in order that desirable results may emerge in human world, enhancing the validity of their contents each other. Here, for example, the exploratory method of multidimensional data analysis and the idea of optimal control with QOL of individuals in medical trials are explained. PMID- 1736828 TI - [Clinical approach to infection in patients with malignancy]. PMID- 1736830 TI - [The strategy against post-operative infection in the patients with esophageal cancer]. AB - Post-operative infection with esophageal cancer patients was investigated. The subjects were 325 esophageal cancer patients. The most frequent infectious complication after the surgery was pneumonia, followed by anastomosis between the cervical esophagus and plastic stomach tube. The bacteria frequently found in infectious lesions were pseudomonas or staphylococcus. The more severe infection the patients had, the more gram negative bacteria were found. Bacterial examination during operation showed that more than 80% bacteria was gram negative. Since esophageal cancer patients had a low nutritional state, their immune function was impaired and infection was apt to occur post-operatively. Therefore, special nutritional care was indispensible, such as essential fatty acid, BCAA, and glutamine supplementation. PMID- 1736829 TI - [Evaluation of the importance of infection as cause of death in patients with malignancy: an analysis of autopsy cases]. AB - The autopsy records of patients who died at Keio University Hospital from January 1, 1970 through December 31, 1974 and from January 1, 1985 through December 31, 1989, were reviewed and their main diseases and the causes of death were determined. The contribution of infections to the death of each patient was classified as follows: Class 1: Infection is the only cause of death. Class 2: Infection is the predominant cause of death. Class 3: Non-infectious disease is the predominant cause of death. Class 4: Infection is independent of patient's death. The total number of autopsy cases and cases with malignancy were 1,140 and 664 in the early 1970's and 1,136 and 826 in the late 1980's, respectively. Patients with hematologic malignancies totalled 90 and 95 in the two periods, respectively. In the early 1970's, 35% of patients with malignancies died of infections [classified as Class 1 (25%) and Class 2 (10%)], and in the late 1980's, 32% of cancer patients died of infections (Class 1 20% and Class 2 12%, respectively). The most important infectious disease was pulmonary infection in the two periods. In patients with other than hematologic cancers (solid cancers), 63% and 58% of patients died of pulmonary infection in the early 1970's and the late 1980's, respectively. The rate of solid cancer patients who died of systemic infection rose from 7% in the early 1970's to 21% in the late 1980's. In hematologic cancer patients, the importance of pulmonary infection and that of systemic infection were comparable in the two periods. Fungus infection in hematologic cancer patients was a serious problem in the two periods, but it became more important in the late 1980's. The most important cause of death of cancer patients in the two periods was the cancers themselves; 39% of patients in the early 1970's and 43% in the late 1980's, respectively, died of marasmus or insufficiency of vital organs due to cancer. PMID- 1736831 TI - [Comparative study of UFT plus mitomycin C and UFT plus doxorubicin in adenocarcinoma. Hirosaki Cooperative Group of Cancer Chemotherapy]. AB - A multicenter cooperative study was conducted to compare the clinical efficacy of UFT-M (UFT, Mitomycin C (MMC)) and UFT-D (UFT, Doxorubicin (DXR)). A total of 62 cases with adenocarcinoma were enrolled in this study. Eligible cases included 25 patients with gastric cancer, 22 with pancreas or biliary tract cancer and 10 with other cancers. They were divided into two groups; 30 in UFT-M and 27 in UFT D. The treatment schedules were as follows: UFT 400-600 mg/day orally every day, MMC 4-6 mg/m2, IV, every week (UFT-M); UFT 400-600 mg/day orally every day, DXR 20 mg/m2, IV, every 3 weeks (UFT-D). For gastric cancer, 3 of 17 cases treated by UFT-M showed PR, whereas no case showed PR in UFT-D. As for toxicity, bone marrow suppression was more commonly observed in UFT-M than in UFT-D. There was no statistical difference in survival between the two treatment regimens. These results suggested that UFT-D was not effective but UFT-M was a more promising combination therapy against advanced gastric cancer. PMID- 1736832 TI - [Preoperative role of angiotensin II induced hypertension chemotherapy (IHC) in advanced gastric carcinoma]. AB - To investigate the role of preoperative IHC in advanced gastric carcinoma, clinical, surgical and pathological stagings of 13 patients were analysed retrospectively. These patients were treated with a 3-drug combination of adriamycin, 5-fluorouracil and mitomycin C under angiotensin II induced hypertensive state. The response rate was 69.2% and mean survival time was 850.2 days. "Down staging" in surgical stage was observed in 5 out of 13 cases (38.3%), and in pathological stage 7 cases (53.8%) "down staging" was achieved. Mean survival time of "pathological down-staging" cases was significantly longer than that of "non-down-staging" cases (1039.6 vs 322.1 days, p less than 0.01, generalized Wilcoxon test). IHC brings selective increase of drug delivery to tumor tissue, and will be useful as preoperative chemotherapy in advanced gastric carcinoma in terms of "down staging". PMID- 1736833 TI - [Neo-adjuvant chemotherapy with cisplatin, 5-fluorouracil, vindesine in head and neck cancer]. AB - Neo-adjuvant chemotherapy with CDDP combination was introduced into the treatment of advanced head and neck cancer. Twenty-three patients with s.c.c of head and neck were given combination chemotherapy consisting of CDDP, VDS and 5-FU before surgical treatment in our department. CR and PR of this trial in all patients were 4 and 35%, respectively. The WBC nadir occurred around 2 weeks later, but all the patients recovered prior to the next cycle or surgical treatment. Renal dysfunction, nausea, vomiting and depilation were generally mild. VDS is useful as one of the neo-adjuvant drugs for the treatment of head and neck cancer. Long term observation in connection with this treatment is required. PMID- 1736834 TI - [Effect of treatment schedule of an antitumor platinum complex, DWA2114R, on the antitumor activity]. AB - Effects of treatment schedule of (-)-(R)-2-aminomethylpyrrolidine (1,1 cyclobutanedicarboxylato) platinum (II) monohydrate, DWA2114R, on the antitumor activity against murine colon adenocarcinoma (Colon 26) and Lewis lung carcinoma (3LL) were examined. Colon 26 or 3LL tumors were transplanted s.c. into the flank and subsequently DW A2114R was given i.v. by single or multiple injections. The tumor weight was determined on days 14 or 25 and the antitumor effect was evaluated by GIR%. Although the total dose of DWA2114R was identical in both schedules, single injection was superior to multiple. Effect of treatment schedule of cis-dichlorodiammine-platinum (II), CDDP, and cis-diammine (1, 1 cyclobutanedicarboxylato) platinum (II), CBDCA, on the antitumor activities were the same as in case of DWA 2114R, i.e., single injection was superior to multiple. PMID- 1736835 TI - [Combination therapy of a new platinum complex, DWA2114R with various antitumor agents against mouse tumors in vivo]. AB - In vivo antitumor activity of (-)-(R)-2-aminomethylpyrrolidine (1, 1 cyclobutanedicarboxylato) platinum (II) monohydrate (DWA2114R) in combination with various antitumor agents was examined using mouse leukemia P388, Meth-A fibrosarcoma and M5076 reticulum cell sarcoma. The combination treatment of DWA2114R with cyclophosphamide, 5-fluorouracil, adriamycin, etoposide or vindesine showed synergistic effects on the prolongation of survival time of mice bearing P388. Among these combinations, combination of DWA2114R with adriamycin or vindesine showed a good synergism. In the combination treatment with vindesine against Meth-A which is not so sensitive to platinum agent, DWA2114R showed a synergistic or additive effect, but cis-diamminedichloroplatinum (II) (CDDP) showed subadditive. Three-drug combination of DWA2114R or CDDP with cyclophosphamide and adriamycin was examined in mice inoculated i.p. or s.c. with M5076. In both models, the combination of DWA2114R was more active than that of CDDP at the dose less than 1/16-fold of the dose of CDDP which is the ratio of two drugs in clinical trial. PMID- 1736836 TI - [A case of recurrent malignant glioma treated by superselective intraarterial chemotherapy with a combination of etoposide and cisplatin]. AB - Superselective intraarterial infusion of etoposide and cisplatin was performed in a patient with recurrent malignant glioma located in the left midbrain extending to thalamus which had progressed after two courses of radiotherapy and chemotherapy with various anticancer agents. Infusion of etoposide (80 mg/m2) and cisplatin (80 mg/m2) at the basilar top did not result in any neurological deficits when infused for 60 minutes with intermittent infusion of papaverine and nicardipine. CT scan carried out 6 days after chemotherapy demonstrated disappearance of the tumor. PMID- 1736837 TI - [A case report of multiple bone metastases of breast carcinoma effectively treated with mild chemo-endocrine therapy]. AB - A woman with multiple bone metastases three years after radical mastectomy for right breast carcinoma was admitted to the Department of Radiology, National Hakodate Hospital. She underwent radiotherapy for the metastasis of the seventh cervical vertebra, and her back pain decreased. Six courses of combination chemotherapy were undertaken using MTX, CPM, 5-FU, VCR and predonine, but her multiple bone metastases progressed. Then, she was treated with chemo-endocrine therapy which consisted of tamoxifen 30 mg daily and CPM 100 mg daily given orally. Two months later, UFT 400 mg daily was administered instead of CPM. This therapy has been effective for 8 years, and she has remained alive and well. On bone scintigram, the abnormal radioisotope uptake almost disappeared. Also, X-ray film showed no osteolytic change and no destruction of bone. These results suggest that it is important to select a suitable combination of drugs for each patient with advanced breast carcinoma. PMID- 1736838 TI - [Standard deviation of inhibition index of chemosensitivity testing using the MTT assay]. PMID- 1736839 TI - [Interaction of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) monohydrate with DNA as determined by a nitrocellulose filter binding assay]. PMID- 1736840 TI - [Intensive carboquone and cryopreserved autologous bone marrow transplantation for relapsed malignancies]. PMID- 1736841 TI - [Studies on a slow releasing anticancer agent for prevention of peritoneal recurrence of advanced gastrointestinal carcinomas (clinical study)]. PMID- 1736842 TI - [Clinical pharmacology of anticancer agents (Part 4). Antimetabolites (1)]. AB - 1. Pharmacodynamics and pharmacokinetics of antimetabolites. Antimetabolites are administered in the form of a base or its riboside, which is incorporated into the cell and converted to an active or inactive metabolite. The active metabolite remain in the cell inhibiting the enzymes to catalyze nucleotide synthesis for nucleotide triphosphate formation, but the inactive metabolites are rapidly excreted out of the cell. The inhibitory effect of antimetabolites on nucleotide formation is correlated with factors, such as maintenance of drug blood level, incorporation of the drug into the cell, activation and inactivation of the drug, affinity of the active form to the corresponding enzyme, and change in pool size of the intermediate metabolites in nucleotide synthesis. The salvage synthesis occurring at the higher level of the enzymes catalyzing nucleotide synthesis to counteract the inhibition by the drug is also correlated with the nucleotide formation. II. Pyrimidine antagonists 1. Cytosine arabinoside (ara-C) and its derivatives Ara-C is rapidly converted to ara-CTP and ara-U. The former remains in the cell and inhibits DNA polymerase, but the latter is excreted rapidly out of the cell. A small portion of ara-C is incorporated into DNA, which results in the degradation of DNA as demonstrated by reduced sedimentation of bulk DNA in alkaline sucrose gradient centrifugation and the ladder DNA fragmentation with a minimum fragment of approximately 180 base pairs and its conjugates in agarose gel electrophoresis. Behenoyl ara-C (BHAC) is highly lipophilic and highly distributed in the erythrocyte stroma and membrane fraction of leukocytes after iv infusion. The incorporated BHAC is released after the plasma BHAC level decreases, which suggests that erythrocytes can be a drug reservoir after iv infusion. Therefore, severe anemia should be treated before BHAC chemotherapy for longer maintenance of the plasma BHAC level. 2. 5-Fluorouracil (5-FU) and its derivatives Activation of 5-FU in the cells is metabolized by uracil metabolizing enzymes to FUMP and FdUMP. FUMP is further metabolized to FdUMP and is also incorporated to RNA. FdUMP produces a ternary complex with thymidylate synthetase and leucovorin; subsequently, conversion of dUMP to dTMP is strongly inhibited. Thus, FUMP and FdUMP inhibit RNA and DNA metabolism, respectively. Enzyme activity during 5-FU metabolism and consequently the degree of inhibition of DNA and RNA syntheses markedly differ with the tumor cell species. This should be taken into consideration when performing chemotherapy of malignancies. PMID- 1736843 TI - [European School of Oncology (ESO)--gastric cancer treatment strategy]. PMID- 1736844 TI - Testosterone, free testosterone, non-sex hormone-binding globulin-bound testosterone, and free androgen index: which testosterone measurement is most relevant to reproductive and sexual function in men with epilepsy? PMID- 1736845 TI - Three-dimensional in vivo mapping of brain lesions in humans. AB - We describe a multistep technique for three-dimensional reconstruction and analysis of brain lesions in vivo, based on the manipulation of magnetic resonance raw data obtained with a special protocol. The technique permits the direct visual identification of neuroanatomical landmarks in each brain specimen and eliminates the need to rely on averaged templates of human brain sections, which can be a source of lesion localization error. The technique also allows for the bidirectional cross-reference between data points in two-dimensional slices and in volume reconstruction and for the projection of subcortical structures onto the three-dimensional cortical surface. The three-dimensional lesion mapping technique can be applied to research with the lesion method in both human and nonhuman primates, to the planning of neurosurgical lesion approach, and to the teaching of neuroanatomy. PMID- 1736846 TI - Supplementary and primary sensory motor area activity in Parkinson's disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine. AB - We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs. PMID- 1736847 TI - Protein redistribution diet remains effective in patients with fluctuating parkinsonism. AB - Forty-three carbidopa-levodopa (Sinemet)-treated parkinsonian patients with protein-sensitive motor fluctuations were started on the protein redistribution diet within the past 48 months. Thirty patients (70%) are still using the diet successfully after more than 12 months (mean duration, 33.6 months; range, 12 to 48 months). The diet was discontinued in the other 13 cases. In 10 of these 13 patients, the protein redistribution diet was discontinued for a variety of reasons, despite continued sensitivity to dietary protein; in only three patients (7%), those with the most severe and complicated disease, was the protein redistribution diet stopped because of its limited therapeutic benefit. The protein redistribution diet is a simple adjunct to the treatment of Parkinson's disease that can significantly prolong the efficacy of levodopa therapy in many fluctuating "end-stage" patients. PMID- 1736848 TI - The neuropsychological features of mitochondrial myopathies and encephalomyopathies. AB - Detailed testing of higher cerebral function was performed in 36 patients with mitochondrial myopathies and encephalomyopathies. Fourteen of these patients were thought to be cognitively impaired on clinical grounds. The assessments included tests of general intellectual ability and focal tests of memory, language, and perception. Twenty-one (58%) of the 36 patients who were tested had evidence of general intellectual deterioration, with focal cognitive deficits of variable degree. Of the remaining 15 patients in whom there was no evidence of general intellectual decline, five displayed focal cognitive deficits. In only 10 patients was there evidence of cerebral dysfunction. The range and extent of cognitive deficits in mitochondrial myopathies are greater than predicted by their clinical presentations. PMID- 1736849 TI - In vivo phosphorus magnetic resonance spectroscopy in multiple sclerosis. AB - Localized phosphorus magnetic resonance spectroscopy at 1.5 T was performed in 39 patients with multiple sclerosis and in 15 healthy controls. The multiple sclerosis spectra showed increased creatine phosphate levels. This increase was correlated with the severity of the handicap and was greater in patients with a progressive course of the disease than in patients with relapsing-remitting disease. No clear abnormalities were observed in the spectra of patients with multiple sclerosis regarding the phosphomonoesters, phosphodiesters, inorganic phosphate, and beta-adenosine triphosphate or with respect to pH values. There was an increased creatine phosphate level in the spectra in relation to a low metabolic state of the brain. PMID- 1736850 TI - Brain-stem auditory evoked potentials in human immunodeficiency virus seropositive patients with and without acquired immunodeficiency syndrome. AB - Brain-stem auditory evoked potentials were recorded in 35 human immunodeficiency virus (HIV)-seropositive subjects from the Centers for Disease Control groups III and IV, 24 HIV-negative drug abusers, and 62 normal healthy controls. None of the patients had evidence of neurological complications. History of alcohol consumption was an exclusion criterion. The values of central conduction times I V and III-V showed significant differences between the HIV-seropositive subjects and normal healthy controls, as well as between the HIV-seropositive subjects and HIV-negative drug abusers. Central conduction times I-III showed no differences between groups, except in the left ear of Centers for Disease Control group IV compared with controls. No statistical differences were found in the central conduction times between HIV-negative drug abusers and normal healthy controls. The results suggest a subclinical involvement of the upper brain stem in HIV infection. It could be produced by direct action of the virus on central nervous system structures. PMID- 1736851 TI - Progressive vision loss. A rare manifestation of familial cavernous angiomas. AB - We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks. PMID- 1736852 TI - Cerebral blood flow deficits in hereditary essential myoclonus. AB - Hereditary essential myoclonus is a disease in which segmental myoclonus is the sole clinical abnormality and whose cause is unknown. It is characterized by an early onset, a benign course, an autosomal dominant pattern of inheritance, the absence of any other neurologic dysfunction, and normal results of auxiliary tests. Cerebral blood flow studies of a father and son with this disease showed a cortical blood flow reduction contralateral to the myoclonus symptoms. We postulate the cause to be a focal unilateral subcortical cerebral lesion, either in the basal ganglia or in the brain stem, with subsequent cortical deafferentation. PMID- 1736853 TI - Neurologic disease described in the Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793. AB - Know Thyself or Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793, was the first of its kind--concentrating on nervous and mental disturbances and marking the beginning of periodical neuropsychiatric publications. The editor, Karl Philipp Moritz, and the contributors, many of them lay people, were particularly interested in disturbances of language and consciousness. Descriptions of epilepsy, Sydenham's chorea, jargon aphasia, and dementia are briefly summarized. The case material from the Journal was soon translated and integrated in later work. The Journal itself and its "empirical" approach became a model for publications that followed. PMID- 1736854 TI - Practice guidelines in neurology. Will they get us where we want to go? PMID- 1736855 TI - The Canadian Health Care System: the shape of things to come? PMID- 1736856 TI - The formation of moisture droplets on the posterior surface of intraocular lenses during fluid/gas exchange procedures. PMID- 1736857 TI - Ophthalmology is the single largest recipient of Medicare specialty disbursements. PMID- 1736858 TI - Falls in elderly patients with glaucoma. PMID- 1736859 TI - Capsulorhexis and corneal magnification. PMID- 1736860 TI - Pemphigus and pemphigoid. PMID- 1736861 TI - Late infectious endophthalmitis from exposed glaucoma setons. PMID- 1736863 TI - Trends in physician income. PMID- 1736862 TI - Superficial granular corneal dystrophy with amyloid deposits. PMID- 1736864 TI - Can aspirin be used safely for patients with proliferative diabetic retinopathy? PMID- 1736865 TI - Spectacles vs contact lenses in the correction of unilateral axial myopia. PMID- 1736866 TI - Sclerochoroidal calcification. AB - We studied 19 patients with sclerochoroidal calcification. The findings were bilateral in 16 patients and unilateral in the remaining three patients. The lesions, which were usually multifocal, had two characteristic appearances, plaque-like and tumorlike. Eleven patients had relatively flat, irregularly shaped, plaque-like, yellow-white lesions located between the arcades and the equator. Eight patients had more elevated tumorlike lesions, ranging up to 6 mm in height. All showed patterns on echography consistent with calcification. The calcification was often documented in both the choroid and sclera; sometimes it appeared only in the choroid, but never only in the sclera. Calcium metabolism appeared to be normal in all but two of the nine patients in whom it was investigated. Idiopathic sclerochoroidal calcification has a characteristic echographic and ophthalmoscopic appearance and may be more common than has been realized. PMID- 1736867 TI - Through curettage in the treatment of chronic canaliculitis. AB - While various techniques have been proposed for the treatment of canaliculitis, there have been no published series that evaluate the efficacy of simple curettage in the treatment of persistent or recurrent canaliculitis. We report the effectiveness of thorough, simple curettage (without canaliculotomy) in 11 patients with chronic canaliculitis. All patients had a history of canaliculitis related symptoms for a minimum of 6 months and clinically detectable canalicular concretions before initial treatment. Thorough, simple curettage (without canaliculotomy) resolved the chronic canaliculitis in all of the patients. Ten of the 11 patients were cured with a maximum of two sessions of curettage. One patient required three treatments of curettage and silicone intubation for common canalicular narrowing to render her free of symptoms. No surgical complications occurred in any of the patients. Our report confirms the effectiveness and low morbidity of thorough curettage in the treatment of persistent or recurrent cases of canaliculitis. PMID- 1736868 TI - Clinical comparison of grafts stored in McCarey-Kaufman medium at 4 degrees C and in corneal organ culture at 31 degrees C. AB - Twenty-eight paired human corneas were preserved in minimal essential medium at 31 degrees C and in McCarey-Kaufman medium at 4 degrees C. These grafts were then transplanted in pairs of patients with keratoconus who were age matched as closely as possible. These pairs received donor corneas from the same donor, so for each pair the donor age and time from death to preservation were the same. Visual acuity, central corneal thickness, and endothelial cell counts were compared. During the 1- to 2-year study period, no statistically significant difference in visual acuity, corneal thickness, or endothelial cell density was found between grafts stored in minimal essential medium and those stored in McCarey-Kaufman medium. PMID- 1736869 TI - Rate and pattern of neuroretinal rim area decrease in ocular hypertension and glaucoma. AB - The neuroretinal rim areas of 123 eyes (from five normal subjects, 75 patients with ocular hypertension, and 43 patients with glaucoma) were measured to determine the rate and pattern of rim area change during 5 to 15 years (mean, 10 years) of follow-up. Fifty-seven percent of the patients with ocular hypertension and 79% of those with glaucoma showed a statistically significant slope of rim area decrease, a high rate of loss being associated with a high initial rim area. Ninety percent of the variation of rim area loss was accounted for by variables other than the ones measured herein, however (age, disc area, initial rim area, and intraocular pressure). The yearly loss of rim area was 0.23% of the initial area in normal subjects, 0.47% and 2.75% in the patients with stable and deteriorating ocular hypertension, respectively, and 3.47% in the patients with deteriorating glaucoma. The pattern of rim area change was linear in 49% of the patients with a statistically significant rim area decrease, episodic in 22%, and curvilinear in 29%. PMID- 1736870 TI - Optic disc size in exfoliative, primary open angle, and low-tension glaucoma. AB - We examined the magnification-corrected optic disc size in 54 patients with exfoliative glaucoma, 61 patients with primary open angle glaucoma, and 50 patients with low-tension glaucoma. The mean optic disc area in low-tension glaucoma was statistically significantly larger than that in primary open angle and exfoliative glaucoma. The mean values of eyes with primary open angle and exfoliative glaucoma did not differ significantly from each other. Frequency distribution of the optic disc size showed, however, that all three diagnostic groups differed significantly from each other. Small discs were more frequent in eyes with exfoliative glaucoma, and large discs were more frequent in eyes with low-tension glaucoma. In primary open angle glaucoma, small and large optic discs were found equally frequently. It is possible that in some eyes large optic discs are vulnerable to even low intraocular pressures due to qualitative properties of the extracellular matrix. PMID- 1736871 TI - Glaucomatous parapapillary atrophy. Occurrence and correlations. AB - Glaucomatous optic nerve damage is typically associated with intrapapillary changes, such as neuroretinal rim loss. In this study, parapapillary chorioretinal atrophy was evaluated in 691 normal eyes, 1081 glaucomatous eyes, and 31 eyes with ocular hypertension. It was significantly larger and occurred more often in the glaucomatous eyes (parapapillary atrophy area, 1.07 +/- 0.83 mm2) (mean +/- SD) than in the normal eyes (0.55 +/- 0.64 mm2) or in the eyes with ocular hypertension (0.55 +/- 0.37 mm2). These differences were significant also for eyes with moderate glaucomatous damage (0.86 +/- 0.62 mm2). Parapapillary chorioretinal atrophy was associated with shallow glaucomatous cupping, diffuse nerve fiber loss, a marked tessellated fundus, and only moderately elevated intraocular pressure. It increased with a decreasing neuroretinal rim area. It showed a spatial correlation to neuroretinal rim loss inside the optic disc. In unilateral glaucoma, it was larger in the affected eye than in the unaffected eye. Parapapillary chorioretinal atrophy is associated with glaucoma. PMID- 1736872 TI - Block excision of cystic and diffuse epithelial ingrowth of the anterior chamber. Report on 32 consecutive patients. AB - From 1980 to 1990, 32 consecutive patients with progressive cystic or diffuse epithelial ingrowth of the anterior chamber were treated successfully with block excision. This technique consists of simultaneous removal of adjacent iris, pars plicata of ciliary body, and all layers of sclera and cornea in contact with the lesion acting as a shell. The resulting defect is covered by a tectonic corneoscleral graft. Twelve patients had suffered from perforating ocular injury, 10 patients had previously undergone cataract extraction, and 10 patients had various causes of epithelial ingrowth. Cystic epithelial ingrowth occurred in 27 patients, diffuse sheetlike epithelial ingrowth occurred in four patients, and one lesion was identified as foreign body granuloma. On histopathologic examination, all but two patients revealed epithelial involvement of the surface of the ciliary body. All patients were followed up for an average of 60.1 months (range, 1 to 120 months). Long-term visual acuity was better than 20/60 in 37.5% of the patients. No recurrence of ingrowth was noted and enucleation was not necessary. Our results indicate that block excision currently may be the treatment of choice for cystic and diffuse sheetlike epithelial ingrowth of the anterior chamber. PMID- 1736873 TI - Subepithelial fibrosis after myopic epikeratoplasty. Report of a case. AB - A 29-year-old man with a -22.00-diopter myopia in the right eye underwent a planar, nonfreeze myopic epikeratoplasty and postoperatively developed a central subepithelial opacity. The opacity recurred after two superficial keratectomies; finally, another epikeratoplasty was performed. Light microscopic examination of the original button showed that the epithelium was thickened, collagenous subepithelial fibrocellular tissue was present, and Bowman's layer was focally disrupted. The stroma was edematous and peripherally scarred with scattered keratocytes. Examination by transmission electron microscopy revealed keratocytes lying anterior and posterior to Bowman's layer. The subepithelial fibrocellular tissue corresponded to an area of a break in Bowman's layer and probably originated from the donor stroma. The break in Bowman's layer may have been caused by the microkeratome cuts, but its origin is not certain. PMID- 1736874 TI - Iris sector heterochromia as a marker for neural crest disease. AB - A 6-month-old female infant with biopsy-proved Hirschsprung's disease had associated sector heterochromia of the irides. The association between sector heterochromia and Hirschsprung's disease has been previously reported and both conditions have been ascribed to neural crest defects. Histologic characteristics of the ocular involvement have not previously been reported, to our knowledge. Histopathologic examination of the globes revealed decreased iris stroma, decreased pigmentation in the anterior stroma, and reduced numbers of pigment producing cells in the affected areas. Both the ocular and gastrointestinal findings reflect abnormalities in tissues of neural crest origin. PMID- 1736875 TI - Choristoma of the optic nerve and chiasm. AB - A 21-year-old patient with a biopsy-proved choristomatous malformation of the optic nerve and chiasm is presented. The patient experienced progressive unilateral vision loss and optic atrophy. A gadolinium-enhanced magnetic resonance image demonstrated chiasmal involvement that was not evident on computed tomographic scan or visual field testing. We believe this is the third reported case of a choristomatous malformation of the optic nerve and chiasm and the first report of magnetic resonance imaging findings. PMID- 1736876 TI - Evaluation of the retinal toxicity and pharmacokinetics of dexamethasone after intravitreal injection. AB - The intravitreal injection of steroids may be potentially useful in the treatment of endophthalmitis and other ocular inflammatory diseases. The retinal toxicity and intraocular turnover of aqueous solutions of dexamethasone sodium phosphate in doses ranging from 440 to 4000 micrograms were evaluated in the rabbit; evaluation was also performed for a 0.1-mL injection of a commercially available preparation (dexamethasone phosphate [Decadron] injection, 4 mg/mL). After the 440-micrograms dose, a transient increase in staining of the Muller cells was observed, which normalized after 2 days. Progressively higher doses resulted in an increasing spectrum of disorganization in Muller and other retinal cells. The half-life of the intravitreally injected drug was 3.48 hours. These findings suggest a primary interference in Muller cell function, possibly through dexamethasone-induced alterations in retinal glutamate or glucose metabolism. PMID- 1736877 TI - A new technique for visualization of the human retinal vasculature. AB - Adenosine diphosphatase, an endothelial cell ectoenzyme that hydrolyses adenosine 5'-diphosphate to adenosine monophosphate, has been used histochemically to study the human retinal vasculature in flat mounts or as flat-embedded tissue that can be sectioned. In all retinas, reaction product was confined almost exclusively to the vasculature, with arteries having more reaction product than veins or capillaries. Adenosine diphosphatase activity was observed in endothelium, smooth muscle cells, pericytes, and erythrocytes. In the more elaborate version of the technique, the adenosine diphosphatase-incubated retinas were flat embedded in glycol methacrylate. This allowed study of the retinal vasculature in dual perspective: en bloc with the use of dark-field microscopy and specific areas of interest histologically sectioned for further evaluation. The technique is simple and preserves angioarchitecture because the retinas are intact, and patency of the vasculature can be determined. PMID- 1736878 TI - Blood-retinal barrier breakdown caused by diode vs argon laser endophotocoagulation. AB - We compared the effects of argon and diode laser endophotocoagulation on blood retinal barrier breakdown using real-time magnetic resonance imaging following intravenous gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injection. Endophotocoagulation was performed on eyes of pigmented rabbits with either the argon or the diode laser to produce ophthalmoscopically similar lesions. Magnetic resonance imaging studies were performed either 2 or 7 days after laser treatment, and coronal T1-weighted proton images were obtained in the first 20 minutes following Gd-DTPA injection. The mean signal intensity over a region of interest in the vitreous cavity was analyzed, and an initial rate analysis was performed on each time-course curve. Two days after treatment, argon laser treated eyes showed significantly greater leakage of Gd-DTPA than diode laser treated eyes. The leakage in both groups was substantially reduced by posttreatment day 7. Histopathologic examination performed 2 days following photocoagulation showed less damage of the retinal pigment epithelium and more severe occlusion of the choriocapillaris and deep choroidal vessels in diode laser-treated eyes. These changes may serve to explain the observed differences in Gd-DTPA leakage. PMID- 1736879 TI - Pituitary adenoma presenting as unilateral proptosis. PMID- 1736880 TI - Lens-sparing vitreoretinal surgery in infants. AB - Lensectomy is routinely performed in infant eyes undergoing vitreoretinal surgery. Using a two-port system, we performed pars plicata vitrectomy and membrane peeling without removal of the crystalline lens. Surgical manipulations were done in the postequatorial region in eyes with areas of attached peripheral retina. Eight of 10 eyes showed no evidence of postoperative cataract formation. In no instance was a peripheral retinal break created. In selected cases, vitreoretinal surgery can be performed in infant eyes without the need for lens removal. PMID- 1736881 TI - Expression, purification and characterization of a mouse-human chimeric antibody and chimeric Fab' fragment. AB - B72.3 is a mouse monoclonal antibody against a tumour-associated antigen, TAG72, which recognizes breast, ovarian and colorectal tumour tissue. A mouse-human chimeric version of B72.3 has been expressed in Chinese-hamster ovary cells. This molecule has the binding specificity of B72.3 and constant regions from human IgG4. The chimeric B72.3 assembles to intact IgG and recognizes TAG72 as well as B72.3 in competitive binding assays. A proportion of the chimeric B72.3 (approx. 10%) does not form inter-heavy-chain disulphide bonds but still assembles into the IgG tetramer. This appears to be a general property of human IgG4 molecules. Co-expression of the chimeric light chain with a chimeric Fd' gene resulted in the expression of functional Fab'. Very little F(ab')2 is produced, although the Fab' can be oxidized to the dimeric F(ab')2 in vitro. The production of Fab' and F(ab')2 by this method is an attractive alternative to proteolytic digestion of IgG. The ability to produce these molecules in large quantities will allow the production and testing of a range of anti-tumour antibody and antibody fragment conjugates. PMID- 1736882 TI - Effects of litter removal on the lipolytic response and the regulatory components of the adenylate cyclase in adipocytes isolated from lactating rats. AB - The effects of litter removal on the status of different components of the hormone-sensitive adenylate cyclase system were analysed in plasma membranes of rat adipocytes. These effects were correlated with the decreased lipolytic response of adipose tissue. No changes in total number of A1 adenosine receptors or their affinity were detected in response to litter removal. In contrast, beta adrenergic receptors showed a decrease (35%) in total number of receptors, without any significant change in their affinity. The status of alpha-GS and alpha-Gi, the alpha-subunits of G proteins which mediate stimulation and inhibition respectively of adenylate cyclase, were probed by cholera- and pertussis-toxin-catalysed ADP-ribosylation respectively and by immunoblot. Associated with litter removal, decreases of 63% and 62% in the incorporation of [alpha 32P]ADP-ribose catalysed by cholera toxin and pertussis toxin into alpha Gs and alpha-Gi respectively were detected. Immunoblotting using RM/1 (anti-alpha Gs) and AS/7 (anti-alpha-Gi) antisera also showed decreases in the levels of alpha-Gs (52%) and alpha-Gi (55%) in adipocyte membranes from litter-removed rats compared with lactating rats. Alterations in the status of hormone-sensitive adenylate cyclase components, such as those described herein, may be biochemical mechanism(s) by which adipose tissue shows a decreased lipolytic response during recovery from lactation. PMID- 1736883 TI - Sensitivity of monomeric and dimeric forms of bovine seminal ribonuclease to human placental ribonuclease inhibitor. AB - We have studied the inhibition of bovine pancreatic RNAase (RNAase A) and bovine seminal RNAase in its native dimeric form (RNAase BS-1) and in monomeric carboxymethylated form (MCM RNAase BS-1) by human placental RNAase inhibitor (RNAase inhibitor) in order to understand the effect of enzyme structure on its response to the inhibitor. Study of the inhibition as a function of inhibitor concentration revealed that RNAase A and MCM RNAase BS-1 were inhibited fully and the inhibitor-sensitivities of the two were comparable. But under identical inhibitor concentrations RNAase BS-1 was found to be virtually insensitive to the inhibitor; at higher (3-10-fold) inhibitor concentrations marginal inhibition of the native enzyme could be observed. When RNAase BS-1 was pretreated with 5 mM dithiothreitol (DTT) and assayed, it exhibited greater inhibitor-sensitivity, presumably as a result of its partial monomerization on exposure to DTT. This DTT mediated change in the response of RNAase BS-1 to the inhibitor did not, however, seem to occur either in the assay conditions (which included DTT) or even when the enzyme was pretreated with DTT in the presence of the substrate, suggesting an effect of the substrate on the enzyme behaviour towards the inhibitor. Independently, gel-filtration runs revealed that, although DTT treatment caused monomerization of RNase BS-1, this change did not take place when DTT treatment was carried out in the presence of the substrate. From our observations, we infer that differential inhibitor-sensitivity of the dimeric and monomeric forms of RNAase BS-1, the relative contents of the two forms and the influence of the substrate on them may be important determinants of the net enzyme activity in the presence of the inhibitor. PMID- 1736884 TI - Mechanistic studies on tyrosinase-catalysed oxidative decarboxylation of 3,4 dihydroxymandelic acid. AB - Mushroom tyrosinase, which is known to convert a variety of o-diphenols into o benzoquinones, has been shown to catalyse an unusual oxidative decarboxylation of 3,4-dihydroxymandelic acid to 3,4-dihydroxybenzaldehyde [Sugumaran (1986) Biochemistry 25, 4489-4492]. The mechanism of this reaction was re-investigated. Although visible-region spectral studies of the reaction mixture containing 3,4 dihydroxymandelic acid and tyrosinase failed to generate the spectrum of a quinone product during the steady state of the reaction, both trapping experiments and non-steady-state kinetic experiments provided evidence for the transient formation of unstable 3,4-mandeloquinone in the reaction mixture. The visible-region spectrum of mandeloquinone resembled related quinones and exhibited an absorbance maximum at 394 nm. Since attempts to trap the second intermediate, namely alpha,2-dihydroxy-p-quinone methide, were in vain, mechanistic studies were undertaken to provide evidence for its participation. The decarboxylative quinone methide formation from 3,4-mandeloquinone dictates the retention of a proton on the alpha-carbon atom. Hence, if we replace this proton with deuterium, the resultant 3,4-dihydroxybenzaldehyde should retain the deuterium present in the original substrate. To test this hypothesis, we chemoenzymically synthesized alpha-deuterated 3,4-dihydroxymandelic acid and examined its enzymic oxidation. Our studies reveal that the resultant 3,4 dihydroxybenzaldehyde retained nearly 90% of the deuterium, strongly indicating the transient formation of quinone methide. On the basis of these findings it is concluded that the enzymic oxidation of 3,4-dihydroxymandelic acid generates the conventional quinone product, which, owing to its unstability, is rapidly decarboxylated to generate transient alpha,2-dihydroxy-p-quinone methide. The coupled dienone-phenol re-arrangement and keto-enol tautomerism of this quinone methide produce the observed 3,4-dihydroxybenzaldehyde. PMID- 1736885 TI - Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics. AB - Cytochrome P450s play a central role in the metabolism and disposition of an extremely wide range of drugs and chemical carcinogens. Individual differences in the expression of these enzymes may be an important determinant in susceptibility to adverse drug reactions, chemical toxins and mutagens. In this paper, we have measured the relative levels of expression of cytochrome P450 isoenzymes from eight gene families or subfamilies in a panel of twelve human liver samples in order to determine the individuality in their expression and whether any forms are co-regulated. Isoenzymes were identified in most cases on Western blots based on the mobility of authentic recombinant human cytochrome P450 standards. The levels of the following P450 proteins correlated with each other: CYP2A6, CYP2B6 and a protein from the CYP2C gene subfamily, CYP2E1 and a member of the CYP2A gene subfamily, CYP2C8, CYP3A3/A4 and total cytochrome P450 content. Also, the levels of two proteins in the CYP4A gene subfamily were highly correlated. These correlations are consistent with the relative regulation of members of these gene families in rats or mice. In addition, the level of expression of specific isoenzymes has also been compared with the rate of metabolism of a panel of drugs, carcinogens and model P450 substrates. These latter studies demonstrate and confirm that the correlations obtained in this manner represent a powerful approach towards the assignment of the metabolism of substrates by specific human P450 isoenzymes. PMID- 1736886 TI - Coupling of D2 dopamine receptors to G-proteins in solubilized preparations of bovine caudate nucleus. AB - 1. The coupling of D2 dopamine receptors and G-proteins has been examined in cholate-solubilized preparations of bovine caudate nucleus. 2. No receptor-G protein coupling could be detected in solubilized preparations obtained in 0.3% cholate, but if this preparation is diluted 5-fold, coupling is re-established. 3. The dilution process was examined, and it was shown that the change in ionic strength was an important factor in modulating the observed receptor-G-protein interaction. 4. Ionic strength was shown, however, not to be the primary determinant of receptor-G-protein coupling. This is likely to be the formation, upon dilution of the preparation, of vesicles in which receptor and G-protein reassociate. 5. The formation of vesicles upon dilution was examined by a variety of techniques, including thermal-stability studies, gel filtration, centrifugation and electron microscopy. PMID- 1736887 TI - Importance of thiol groups in ligand binding to D2 dopamine receptors from brain and anterior pituitary gland. AB - The effects of the thiol group reagent 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) on D2 dopamine receptors have been examined in three brain regions (caudate nucleus, putamen and olfactory tubercle), and in the anterior and neurointermediate lobes of the pituitary gland. Whereas the receptors in brain were insensitive to DTNB, a dose-dependent inhibition of [3H]spiperone binding to D2 receptors in both lobes of the pituitary gland was observed. The effects in the pituitary could be reversed by subsequent treatment with dithiothreitol and could be prevented by prior occupancy of the receptor binding site with a ligand. The effect of DTNB was to decrease the number of ligand-binding sites without altering the affinity of those remaining. The results show that modification of a thiol group of the D2 dopamine receptor in the two lobes of the pituitary gland tested here significantly affects ligand binding. There is therefore a difference between the D2 dopamine receptor populations in brain and pituitary in their sensitivity to modification by DTNB, and this may imply the existence of different receptor isoforms in the two issues. PMID- 1736888 TI - Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver. AB - Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver. PMID- 1736889 TI - Isolation of cleaved prolactin variants that stimulate DNA synthesis in specific cell types in rat pituitary cell aggregates in culture. AB - Using an affinity column of monoclonal antibodies against rat prolactin (PRL), PRL immunoreactive material secreted by rat pituitary aggregate cell cultures was purified in milligram amounts from the culture medium. Further purification of the PRL immunoreactive molecules was achieved by anion-exchange and reversed phase h.p.l.c. At least four variants could be distinguished which showed PRL like bioactivity in the Nb2 lymphoma bioassay. On SDS/PAGE two variants migrated as single bands under both reducing and non-reducing conditions. The two other variants migrated as single bands under non-reducing conditions, but yielded under reducing conditions two fragments, the larger of which had molecular masses of approx. 16 and 17 kDa respectively. These variants were therefore considered to be cleaved PRL (clPRL) variants, and were designated clPRL-1 and clPRL-2 respectively. These variants were not artefactually produced at low pH during the h.p.l.c. purification step. Each of the clPRLs represented about 0.6-1.0% of total PRL. The cleavage site of clPRL-1, determined by N-terminal and C-terminal amino acid sequence analysis, was in the large disulphide loop between Tyr-145 and Leu-146. Purified clPRL-1 added to pituitary aggregate cell cultures from 14 day-old female rats in the presence of the dopamine agonist bromocriptine increased [3H]thymidine incorporation into DNA in gonadotrophs and thyrotrophs, but not in other pituitary cell types. Under the same experimental conditions the main forms of PRL and clPRL-2 were inactive. These data demonstrate that PRL is cleaved within the pituitary gland between specific amino acid residues, and that PRL cleaved between Tyr-145 and Leu-146 may have a specific biological role as a paracrine growth regulator in this tissue. PMID- 1736890 TI - Wheat and barley allergens associated with baker's asthma. Glycosylated subunits of the alpha-amylase-inhibitor family have enhanced IgE-binding capacity. AB - A 16 kDa protein, designated CM16*, which strongly binds IgE from baker's-asthma patients has been identified as a glycosylated form of the previously reported WTAI-CM16, which is a subunit of the wheat tetrameric alpha-amylase inhibitor. A glycosylated form (CMb*) of BTAI-CMb, the equivalent inhibitor subunit from barley, has been also found to have significantly enhanced IgE-binding capacity. In all, 14 purified members of the alpha-amylase/trypsin-inhibitor family showed very different IgE-binding capacities when tested by a dot-blot assay. The glycosylated components CM16*, CMb* and the previously described non-glycosylated 14.5 kDa allergen from barley (renamed BMAI-1) were found to be the strongest allergens. PMID- 1736891 TI - Differential sensitivity of insulin- and adaptive-regulation-induced system A activation to microtubular function in skeletal muscle. AB - 1. Insulin and adaptive regulation are known to stimulate system A amino acid transport activity in skeletal muscle. The present study was designed to investigate whether activation of system A in muscle is a consequence of processes which rely on microtubule or microfilament function. To that end, extensor digitorum longus (EDL) muscles were incubated in the presence of colchicine and cytochalasin D, well-known inhibitors of microtubule and microfilament activity respectively. 2. Basal alpha-(methyl)aminoisobutyric acid (MeAIB) uptake decreased after incubation with 5 microM-colchicine in a time dependent manner. In keeping with this, adaptive regulation of MeAIB uptake caused by prolonged incubation in the absence of amino acids was substantially decreased in the presence of colchicine. 3. Under these conditions, stimulation of MeAIB uptake by insulin was unaltered in muscle in the presence of colchicine. This contrasted with the insulin-induced stimulation of MeAIB uptake by isolated rat hepatocytes, which was markedly decreased by colchicine. 4. Cytochalasin D, an agent that disrupts microfilaments, did not inhibit basal or insulin stimulated MeAIB uptake by the incubated muscle. 5. Neither colchicine nor cytochalasin D modified the stimulatory effect of insulin on 3-O-methylglucose uptake by EDL muscle. 6. We conclude that up-regulation of system A by synthesis of new carriers depends on the integrity of microtubular function both in skeletal muscle and in hepatocytes. Microtubules might play a role in the movement of system A-containing vesicles from the Golgi network to the plasma membrane. PMID- 1736892 TI - Insertion of isolated insulin receptors into placental membrane vesicles. AB - Purified human insulin receptors were inserted into placental plasma-membrane vesicles by fusion of membranes with receptor-lysophosphatidylcholine micelles. Scatchard analysis of insulin binding showed that about 10-15% of the added receptors became inserted into the membrane. The receptor number could be increased about 3-fold, corresponding to approx. 5 pmol of receptor/mg of membrane protein. The receptors became firmly bound to the membrane, as they could not be removed by extensive wash. The insertion of exogenous receptors could be demonstrated by immunoblotting. The inserted insulin receptor had the same insulin-binding affinity as the isolated receptor and the endogenous receptor of the membrane. Insulin binding in the presence or absence of Triton X 100 revealed that more than 80% of the exogenous receptors had a right-side-out orientation. Function of the inserted receptors, as observed by insulin stimulated autophosphorylation, could be demonstrated. About 80% of the added lysophospholipid, corresponding to approx. 160 nmol of lysophospholipid/mg of membrane protein, became integrated into the membrane and was partly metabolized to phospholipid and to non-esterified fatty acid. The method of insertion of isolated insulin receptors using the natural detergent, lysophospholipid, may be a method for insertion of receptors into intact cells, where the lysophospholipid, as in the plasma-membrane vesicles, will be acylated to phospholipid. PMID- 1736893 TI - Glucose induces the translocation and the aggregation of glycogen synthase in rat hepatocytes. AB - Incubation of rat hepatocytes with glucose results in a decrease in the amount of glycogen synthase activity found in supernatants obtained after centrifugation of cell homogenates at 9200 g. The enzymic activity was quantitatively recovered in the sediments. This effect of translocation was dose- and time-dependent and correlated with the amount of immunoreactive enzyme determined by immunoblotting in both fractions. Hydrolysis by alpha-amylase of glycogen accumulated upon incubation with the sugar did not affect the translocation pattern. Translocation was also observed when cells were incubated with 2-deoxyglucose, which did not result in accumulation of glycogen. Immunocytochemical evidence indicates that glucose induces the aggregation of glycogen synthase molecules into clusters which are recovered in the sediments. These results indicate that glucose, in addition to activating glycogen synthase, may trigger changes in the localization of the enzyme in the cell. PMID- 1736894 TI - Role of protein kinase C in the acrosome reaction of mammalian spermatozoa. AB - Mammalian spermatozoa undergo a Ca(2+)-dependent exocytotic event before fertilization which is known as the acrosome reaction. The process of exocytosis in several cell systems is mediated by a protein kinase C (PKC)-catalysed phosphorylation. Addition of phorbol 12-myristate-13-acetate or the membrane permeant diacylglycerol analogue 1-oleoyl-2-acetylglycerol, which are potent activators of PKC, to bovine spermatozoa resulted in stimulation of the acrosome reaction. This stimulation was inhibited by low concentrations (50% inhibition at 0.7 nM) of the PKC inhibitor staurosporine. PKC specific activity in bovine spermatozoa is extremely low in comparison with other cells; however, it is comparable with the activity found in human spermatozoa. Immunohistochemical analysis using anti-PKC antibodies revealed staining in the equatorial segment, the post-acrosomal region and the upper region of the head. We propose that PKC is involved in the mammalian sperm acrosome reaction. PMID- 1736895 TI - Polymorphism and proteolytic fragments of granulocyte membrane cofactor protein (MCP, CD46) of complement. AB - Human granulocytes (polymorphonuclear leucocytes, PMN) possess a membrane cofactor protein (MCP, CD46), which is structurally and functionally distinct from the MCPs of other cell types: it shows a single broad band of 56-80 kDa (without the doublet pattern characteristic of MCP) on SDS/PAGE and has less affinity for complement component C3b. We purified PMN MCP using monoclonal antibodies in order to study the molecular differences between it and other MCPs. Several forms of PMN MCP with size heterogeneity were noted on SDS/PAGE and by immunoblotting. O-Glycanase treatment decreased this heterogeneity, yielding a fast-migrating component identical in position on SDS/PAGE to the O-glycanase treated MCP of other cells. The cell-specific variation of MCP, therefore, arises from post-translational glycosylation and not from a difference in primary structure. The Factor I cofactor activity of PMN MCP was more efficient in cleaving the methylamine-treated complement components C4/C3 than was MCP from other cells, which shared a similar potency of cofactor activity on a weight basis. Two types of small-form PMN MCP were identified during purification. These were 42 kDa and 30 kDa in size; the former was recognized by M177 (a monoclonal antibody against the active site marker), possessed N-linked sugars [located on the short consensus repeats (SCRs)] but not O-linked ones (on the Ser/Thr-rich region), and retained cofactor activity for C3b/C4b cleavage, similar in potency to that of other MCPs. The functionally active soluble form of MCP was observed specifically in PMN. Protease inhibitors did not inhibit liberation of the fragments, although the generated fragments became susceptible to serine proteases. The findings show that the SCRs are the functional domain of MCP and that the MCP proteolysis found only in PMN may modulate the properties of PMN MCP. In conclusion, the structural features of PMN MCP largely reflect a variability in the O-linked sugars, and the decreased affinity for C3b may be in part attributable to proteolysis. PMID- 1736896 TI - The pattern of plant annexin gene expression. AB - Peptide sequence data derived from a plant annexin, P34 [Smallwood, Keen & Bowles (1990) Biochem. J. 270, 157-161] was used to design amplimers for PCR. A unique fragment of 95 bp, amplified from tomato (Lycopersicon esculertum) genomic DNA, was used in Northern analyses and demonstrated a differential pattern of expression in vegetative tissues of tomato, potato (Solanum tuberosum) and barley (Hordeum vulgare). The tissue-specific abundance of the annexin transcript was found to correlate closely with abundance of annexin protein as revealed by their partial purification and analysis with antisera specific for annexins isolated from tomato suspension-culture cells. PMID- 1736897 TI - 'Macromolecular crowding' is a primary factor in the organization of the cytoskeleton. AB - We propose that, in the cell, the reversible conversion of actin filaments into actin bundles is controlled by the concentration of the macromolecules [we have employed poly(ethylene glycol) 6000 to mimic the macromolecules of the cell] as well as by the nature of the ancillary cytoskeletal proteins that decorate actin filaments. The proposal is based on the following evidence. (1) Under our experimental conditions the transition from filaments into bundles occurs at increasing concentrations of poly(ethylene glycol), with the following sequence: caldesmon-actin, 3%; filamin-actin, 4-5%; caldesmon-tropomyosin-actin, 5-7%; actin, 6-7%; tropomyosin-actin, 9-10%. (2) Under conditions of low osmoelastic stress [3% poly(ethylene glycol)], preformed caldesmon-actin bundles are dissociated by the addition of either tropomyosin or tropomyosin-decorated actin. The dissociation of the bundles promoted by the addition of tropomyosin-decorated actin is faster than that promoted by the addition of tropomyosin. PMID- 1736898 TI - Molecular analysis of Xenopus laevis SPARC (Secreted Protein, Acidic, Rich in Cysteine). A highly conserved acidic calcium-binding extracellular-matrix protein. AB - SPARC (Secreted Protein, Acidic, Rich in Cysteine) is expressed as a 1.6 kb mRNA in Xenopus laevis. On the basis of cDNA sequence analysis, Xenopus SPARC has a core Mr of 32643, with one potential N-glycosylation site. Western analysis of SPARC isolated from Xenopus long bone indicates that the mature protein has an Mr of 43,000. At the amino acid level, Xenopus SPARC has 78-79% sequence similarity to mouse, bovine and human SPARC. The least-conserved region is found within the N-terminal glutamic acid-rich domain, with the C-terminal Ca(2+)-binding domain being the most conserved. Adult Xenopus tissues show the same pattern of tissue specific distribution of SPARC mRNAs as adult mouse. PMID- 1736899 TI - Purification and characterization by fast-atom-bombardment mass spectrometry of the polymorphonuclear-leucocyte-elastase-generated A alpha (1-21) fragment of fibrinogen from human blood after incubation with calcium ionophore A23187. AB - The stimulation of human blood with a Ca2+ ionophore, A23187, leads to activation of polymorphonuclear leucocytes (PMN) with release of small amounts of catalyticaly active elastase, as demonstrated by the formation of a characteristic product, the N-terminal A alpha (1-21) peptide of the Aa subunit of fibrinogen. The identity of the peptide was initially established by radioimmunoassay (r.i.a.) with an antibody raised to A alpha (1-21). We now provide independent confirmation of the formation of A alpha (1-21) by fast-atom bombardment-m.s. analysis of the fractions separated chromatographically after spiking of plasma samples with peptide labelled with [2H8]Phe at position 8. Identity of the peptides was established on the basis of their chromatographic retention time and by the distinct peaks in the mass spectra of these fractions. The relative intensities of the molecular ions of natural and labelled peptides were measured. On the basis of a comparison of the peaks of similar intensities, the concentration of the natural peptide at the time of spiking was close (79%) to the amount obtained by r.i.a. An additional peptide, des-alanyl-A alpha (2 21), was also seen. The total amount of material measured by r.i.a. could be accounted for by the sum of these two provides. The addition of label and assay by m.s. has provided an independent physical-chemical method for identifying A alpha (1-21) as a characteristic product of PMN elastase release in whole blood, but which is absent in freshly drawn blood. PMID- 1736900 TI - Effects of cyclofenil diphenol, an agent which disrupts Golgi structure, on proteoglycan synthesis in chondrocytes. AB - 1. Cyclofenil diphenol (F6060), a weak non-steroidal oestrogen, was shown previously to inhibit [35S]proteoglycan synthesis [Mason, Lineham, Phillipson & Black (1984) Biochem. J. 223, 401-412] and to induce fragmentation of the Golgi apparatus into small vesicles [Lancaster, Fryer, Griffiths & Mason (1989) J. Cell Sci. 92, 271-280] in cultures of Swarm chondrosarcoma chondrocytes. Two structurally related compounds, F6204 and F6091, show a similar concentration related effect, with complete inhibition of [35S]proteoglycan synthesis at 90 micrograms/ml. The apparent [3H]protein synthesis is only approx. 40% inhibited with [3H]lysine as precursor. Stilboestrol, clomiphene and tamoxiphen are also potent inhibitors of [35S]proteoglycan synthesis. 2. Syntheses of chondroitin 4 [35S]sulphate and chondroitin 6-[35S]sulphate, which are Golgi-mediated events, are inhibited 40-68% and 3-48% respectively by concentrations of cyclofenil between 50 and 70 micrograms/ml. [3H]Hyaluronan synthesis, which occurs by a different mechanism at the plasma membrane, is inhibited by 47-66%. These results suggest that cyclofenil may act via more than one inhibitory mechanism. Cyclofenil diphenol inhibits polymerization of chondroitin sulphate on to p nitrophenyl beta-xyloside even when the chondrocytes are loaded with the initiator prior to treatment. 3. Cyclofenil diphenol interferes with the cellular uptake of amino acids via the system A carrier, as shown by inhibition of uptake of methylaminoisobutyric acid, a specific substrate for this system. The drug had no effect on the uptake of 2-deoxyglucose by the cells. 4. Cyclofenil diphenol (90 micrograms/ml) caused a decrease in the pool size of UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine and UDP-hexoses, but this was insufficient to account for the accompanying profound inhibition of [35S]proteoglycan synthesis. Entry of [3H]glucosamine into the cell and into the UDP-N-acetylhexosamine pool did not appear to be affected. 5. Cyclofenil diphenol inhibited the substitution of 3H labelled proteoglycan core protein with chondroitin sulphate chains. Core protein was identified in treated cultures on the basis of immunoprecipitation with an antiserum against the hyaluronate-binding region and distinguished from precipitated proteoglycan on SDS/PAGE. PMID- 1736901 TI - Deficiency of 5'-deoxy-5'-methylthioadenosine phosphorylase activity in malignancy. Absence of the protein in human enzyme-deficient cell lines. AB - The absence of 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAase) activity in malignant cells, and the putative localization of its gene, suggest that this enzyme deficiency might be due to a genomic alteration also involving a tumour suppressor gene. We studied the possible occurrence of inactive forms of the protein in two MTAase-negative cell lines, namely K562 and Jurkat, by immunochemical methods. Two highly specific antisera, directed against different epitopes of the phosphorylase [Della Ragione, Oliva, Gragnaniello, Russo, Palumbo & Zappia (1990) J. Biol. Chem. 265, 6241-6246], were used to carry out immunotitration and immunoblotting analyses, as well as to investigate the biosynthesis of the enzyme. No MTAase protein was detected by Western-blotting technique performed under conditions where all the phosphorylase-positive samples gave a clear band at the MTAase subunit molecular mass. No cross-reacting material was observed by a sensitive immunotitration method which permitted the detection of as low as 0.5 ng of protein. Moreover, the results obtained by [35S]methionine-labelling experiments ruled out phosphorylase biosynthesis in the negative cell lines. Altogether, these data suggest that an alteration at the gene level hampering the specific mRNA biosynthesis or resulting in an untranslatable mRNA is the cause of the enzyme deficiency in the MTAase-negative cell lines studied. PMID- 1736902 TI - Induction of glutathione S-transferase P-form in primary cultured rat liver parenchymal cells by co-planar polychlorinated biphenyl congeners. AB - Alterations in protein synthesis in primary cultured rat liver parenchymal cells were examined after their exposure to the potent carcinogens, polychlorinated biphenyl (PCB) congeners. Co-planar PCB congeners (3,4,5,3',4'-PCB and 3,4,5,3',4',5'-PCB) (10 nM) induced a protein, the Mr of which was 25,000 (25 k protein) under denaturing conditions. However, non-co-planar PCB congeners and several xenobiotics, which induce microsomal proteins, did not induce the 25 k protein. By using immunoblotting, the 25 k protein was identified as glutathione S-transferase P-form (GST-P, 7-7, EC 2.5.1.18). PMID- 1736903 TI - Variation in the P2-S2 stereochemical selectivity towards the enantiomeric N acetylphenylalanylglycine 4-nitroanilides among the cysteine proteinases papain, ficin and actinidin. AB - 1. Values of the kinetic specificity constant, kcat./Km, for the hydrolysis of N acetyl-L-phenylalanylglycine 4-nitroanilide (I) and of its D-enantiomer (II) catalysed by ficin (EC 3.4.22.3) and by actinidin (EC 3.4.22.14) at pH 6.0, I 0.1 mol/l, 8.3% (v/v) NN-dimethylformamide and 25 degrees C were determined by using initial-rate data with [S] much less than Km and weighted nonlinear regression analysis as: for ficin, (kcat./Km)L = 271 +/- 6 M-1.s-1, (kcat./Km)D = 2.9 +/- 0.1 M-1.s-1, and for actinidin (kcat./Km)L = 13.3 +/- 0.7 M-1.s-1, (kcat/Km)D = 0.34 +/- 0.01 M-1.s-1.2. These data and analogous values for the corresponding reactions catalysed by papain (EC 3.4.22.2), (kcat./Km)L = 2064 +/- 31 M-1.s-1, (kcat./Km)D = 5.5 +/- 0.1 M-1.s-1, demonstrate marked variation in stereochemical selectivity for substrates (I) and (II) among the three cysteine proteinases with the following values for the index of stereochemical selectivity Iss = (kcat./Km)L/(kcat./Km)D: for papain, 375; for ficin 93; for actinidin 39. 3. Model building suggests ways in which, for the papain-catalysed reactions, binding interactions involving the extended acyl groups of the substrates may need to change as the reaction proceeds from adsorptive complex (ES) to tetrahedral intermediate (THI) before its rate-determining, general acid catalysed collapse to acylenzyme intermediate. In particular, satisfactory alignment in the catalytic site at the THI stage of the acylation process appears to demand rotation of the substrate moiety about its long axis. 4. The different consequences of this rotation for the L- and D-enantiomers suggest that for closely related systems the greater the extent of this rotational adjustment the greater would be the value of Iss.5. For the actinidin-substrate combinations, model building suggests that even at the ES complex stage of catalysis it is not possible to approach optimized P2-S2 contacts and the three hydrogen-bonding interactions deduced for papain-ligand complexes in the absence of significant movement of protein conformation. Possible binding modes in which some of the interactions deduced for papain are relaxed are discussed. Consideration of postulated binding modes in the various transition states is shown to account for the order of reactivity reflected in values kcat./Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1736905 TI - Serum magnesium levels in asthmatic patients during acute exacerbations of asthma. AB - The purpose of this study was to determine whether serum magnesium levels in asthmatic patients during acute exacerbations differ from those of a control population. Twenty-three known asthmatics presenting to the emergency department in acute exacerbation (cases) and 15 nonasthmatic patients (controls) matched for age, sex, race, and socioeconomic status had serum magnesium assays drawn. Admission criteria were: age 18 to 50 years with no history of alcoholism, heart disease, renal disease, or diuretic use. Patients giving a history of pregnancy were excluded. Serum magnesium levels were not significantly different in the two study populations, nor did they correlate with the severity of asthma (mean values: cases, 2.04 +/- 0.159 versus controls, 2.03 +/- 0.134 mg/dL; SD of the difference of the means = .048). An analysis for beta-error demonstrated the true difference of the means to be less than .1 (95% confidence) or less than .13 (99% confidence). In conclusion, serum magnesium levels in asthmatics are not significantly different from those of a control nonasthmatic population. They are not clinically useful for predicting the severity of disease. PMID- 1736904 TI - Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes. AB - Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation. PMID- 1736906 TI - Interobserver agreement in the examination of acute ankle injury patients. AB - The authors' objective was to describe a method for measuring interobserver agreement and to determine the reliability of physical findings used by emergency physicians to assess ankle injury patients. A 3-month prospective survey was designed for use in the emergency departments of two university hospitals. Participants were a convenience sample of 100 adult blunt ankle injury patients. Pairs of emergency staff physicians assessed 22 standardized physical findings in each patient without knowledge of the other assessment. Agreement for each variable was measured by the kappa coefficient, the ratio of actual agreement to potential agreement beyond chance. The variables with the highest interobserver agreement and their kappa values were ability to bear weight (.83); bone tenderness at the base of the fifth metatarsal (.78), at the posterior edge of lateral malleolus (.75), and at the tip of the medial malleolus (.66); and combinations of bone tenderness (.76). Less reliable variables included soft tissue tenderness (.41) or degree of swelling (.18) of the anterior talofibular ligament, ecchymosis (.39), range of motion (.33), bone tenderness at the proximal fibula (-.01), and the anterior drawer sign (-.03). High kappa values indicate that several physical findings, including ability to bear weight and selected sites of bone tenderness, may be reliably assessed in ankle injury patients. This knowledge may give physicians more confidence in their physical examination and allow development of reliable clinical guidelines to diminish the reliance on radiography in ankle injuries. PMID- 1736907 TI - Visualization of ingested medications in the stomach by ultrasound. AB - The authors describe a potential application of ultrasound in detection of pills in the stomach, and report the first case of its use in a patient. Thirty pills were studied in vitro by ultrasound. All were clearly detected, with better imaging compared with plain radiography. Four pills with slow disintegration (sustained release or enteric coated) and two with fast disintegration (immediate release) were further studied by ultrasound, following their ingestion by human volunteers. All four pills with slow disintegration were clearly visualized in the stomach, while detection of the other two pills was inconsistent. A sustained release phenytoin capsule was detected by ultrasound in the stomach of a patient 3 hours after its ingestion. Ultrasound is a potential diagnostic tool in detection of pills in the stomach following acute ingestion. Its use, however, seems to be limited to sustained-release or enteric-coated preparations. PMID- 1736908 TI - Intracranial injury following minor head trauma. AB - One hundred twelve patients presenting with a Glascow Coma Scale (GCS) score greater than or equal to 13 with a history of minor head trauma were prospectively studied to determine if certain historic or physical examination variables would predict which of these patients were at increased risk for intracranial injury. Patients either underwent cranial computed axial tomography (CT) or were followed up by phone at 4 weeks to determine major morbidity or mortality. Thirty-five patients underwent CT scanning of the head and eight demonstrated intracranial injury. Five patients were treated nonoperatively, and three patients had neurosurgical intervention. One patient died following surgery. At the 4-week follow-up no patient was found to have suffered any major morbidity or mortality. Stepwise logistic regression found age over 40 years (P = .05, odds ratio = 6.4, 95% confidence interval 1.0 to 38.8) and complaint of headache (P = .039, odds ratio 8.167, 95% confidence interval 1.074 to 62.09) to be significantly predictive of intracranial injury. All eight patients with positive CTs had a GCS score of 15. The authors conclude that intracranial injury does exist in patients suffering minor head trauma with a GCS score of 13 or above. Age over 40 years and complaint of headache are associated with an increased risk of intracranial injury. PMID- 1736909 TI - Long-term local effects of intraosseous infusion on tibial bone marrow in the weanling pig model. AB - The weanling pig model was used to determine the long-term local effects, if any, on tibial bone marrow after intraosseous (IO) infusion of resuscitation fluid and drugs at standard dosages. One of six IO treatments (two normal saline boluses [20 mL/kg]; bolus sodium bicarbonate [1 mEq/kg]; 10% sodium bicarbonate infusion at a maintenance rate for 1 hour; bolus 1:10,000 epinephrine [0.01 mg/kg]; 1:10,000 epinephrine solution infusion, 1 microgram/kg/min for 1 hour; or dopamine infusion, 10 micrograms/kg/min for 1 hour) was randomly administered via the left tibia to 18 pigs at 4 weeks of age. The animals were subsequently followed for 3 months, after which marrow from the same space and peripheral blood were examined. Marrow from the right tibia of each animal served as control; untreated historic controls were also used for comparison. Examination of the marrow revealed normal cell differentials in all limbs in all groups. Overall cellularity was somewhat decreased in the experimental limbs of the normal saline bolus group when compared with same-animal control limbs, perhaps due to the pressure effect from rapid injection. Peripheral blood counts and differentials in these and all other animals were normal. The authors conclude that IO administration of commonly used resuscitative medications does not result in significant adverse effects in the tibial bone marrow in this model. PMID- 1736910 TI - Internal cardiac massage and mediastinal irrigation in hypothermic cardiac arrest. AB - Two unconscious patients with unknown past medical histories were found to be severely hypothermic, with core temperatures of 80.2 degrees F and 86.7 degrees F, respectively. During the course of active internal rewarming, both patients sustained a cardiac arrest. Emergency thoracotomies were immediately done, and internal cardiac massage with warmed mediastinal irrigation was performed. Spontaneous cardiac activity developed in both patients. Within 24 hours after resuscitation, both patients were responsive and following commands. PMID- 1736911 TI - Bedside ultrasound in decision making for emergency surgery: its role in medical intensive care patients. AB - During an 18-month period the authors followed 1,024 patients referred to a general medical intensive care unit. A total of 7% of these patients underwent emergency surgery at some point during their admission. The role of abdominal ultrasound in the decision-making process for these emergency surgical interventions was evaluated and the patients were identified for whom the pathologic result of sonography was regarded sufficient to operate without any additional imaging procedures. Of 71 patients with unexpected surgical emergencies, abdominal ultrasound provided a definite diagnosis for 18 patients (25%), and the decision to operate could be made without delaying for further or more invasive diagnostic techniques. In all cases the sonographic diagnosis was confirmed during the operation. The critical care patients most likely to benefit from bedside ultrasound in a surgical emergency were those with hemorrhage of unknown origin (44%) or septicemia from an undetected focus (39%). The most frequent site of operation where ultrasound was considered diagnostic was the urinary tract (56%), particularly in emergencies following renal transplantation. PMID- 1736912 TI - Arteriovenous malformation of the vein of Galen: a rare cerebral arteriovenous malformation. AB - A 32-year-old male presented to the emergency department for evaluation of a 12 day history of altered mental status. Workup revealed the presence of an arteriovenous malformation (AVM) of the great vein of Galen, an exceedingly rare and often fatal type of cerebral vascular malformation. Concurrent aneurysmic dilatation of the vein, a frequent finding associated with this type of AVM, resulted in compression of the aqueduct of Sylvius and acute hydrocephalus. A brief review of cerebral AVMs is presented, with specific attention to the pathophysiology, clinical presentation, and emergent treatment of those that involve the vein of Galen. PMID- 1736913 TI - Prehospital bicarbonate use in cardiac arrest: a 3-year experience. AB - The American Heart Association no longer recommends the routine use of sodium bicarbonate in cardiac arrests. Reasons cited include the lack of documented effect on clinical outcome and potential adverse effects of metabolic alkalosis and hypernatremia. We reviewed 36 months of experience with 619 nontrauma adult, prehospital cardiac arrest patients to identify 273 successful resuscitations who had emergency department blood gases and electrolytes performed. Determination of complications associated with prehospital intravenous sodium bicarbonate and its impact on survival in resuscitated patients was undertaken. Fifty-eight patients did not receive sodium bicarbonate (NO HCO3 group) and had short cardiopulmonary resuscitation (CPR) times (7.4 +/- 5.5 minutes). Two hundred fifteen patients did receive sodium bicarbonate (HCO3 group) and had significantly longer CPR times (23.3 +/- 13.5 minutes, P less than or equal to .001). Both groups demonstrated routine early chest compression and hyperventilation as evidenced by no significant difference in paramedic response time or rate of intubations. Initial emergency department blood gas results of both groups were not significantly different. No patients in the NO HCO3 group had hypernatremia (sodium [Na]+ greater than 150), whereas four patients (2%) in the HCO3 group were hypernatremic. Eight patients (14%) in the NO HCO3 group and 37 patients (17%) in the HCO3 group were alkalotic with pH values greater than 7.49 (P = NS). Six patients (10%) of the NO HCO3 group and 24 patients (11%) of the HCO3 group had a metabolic component to the alkalosis as defined by a positive base excess value (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736914 TI - Pediatric chest pain: case report of a malignant cause. AB - Pediatric chest pain is not an uncommon presenting complaint in the emergency department. Although the majority of cases are benign, the authors report on a patient with a fetal case of myocarditis. A discussion of myocarditis and its management as well as differential diagnosis is included. PMID- 1736915 TI - Peripartum cardiac failure in a woman with Graves' disease. AB - A case of peripartum cardiac failure is reported in a 20-year-old gravida 3, para 3 black female. The patient was 6 weeks postpartum. Graves' disease had been diagnosed in the first trimester of her pregnancy. The patient presented to the emergency department with complaints of fever, abdominal pain, shortness of breath, and chest pain. Physical examination revealed signs of congestive heart failure and anasarca. Chest x-ray revealed bilateral pleural effusions, and an abdominal series was consistent with ascites. Bedside electrocardiogram revealed pan-hypokinesis of all four cardiac chambers. The authors believe that this is the first case reported in the literature of peripartum cardiac failure occurring in a patient with Graves' disease. PMID- 1736916 TI - Simultaneous bilateral spontaneous pneumothorax: case report. AB - A 22-year-old previously healthy male was admitted to the emergency department for chest pain and dyspnea of 1-day's duration. He had a history of heavy smoking. The patient was cyanotic, agitated, and severely dyspneic. Lung auscultation revealed severe diffuse bronchospasm and equally diminished breath sounds on both sides. Nasotracheal intubation and mechanical ventilation were performed shortly after admission due to acute respiratory failure. Simultaneous bilateral spontaneous pneumothorax was diagnosed from the chest x-ray, and chest tube drainage was immediately performed bilaterally. Computerized tomography of the chest 1 month later showed diffuse emphysematous bullae of the lungs. The case presented here should increase physicians' awareness of this rare form of spontaneous pneumothorax and its diverse manifestations. PMID- 1736917 TI - Safety of pre-hospital therapy with morphine sulfate. AB - The safety of prehospital pharmacologic therapy has not been well studied. The authors evaluated field use of morphine sulfate (MS) in San Francisco County over a 6-month period. Paramedics assessed patients for ischemic chest pain (ICP) and/or pulmonary edema (PE), made base hospital contact, and administered 2- to 4 mg doses of intravenous morphine according to treatment protocols. Clinical assessments and patient responses to therapy were recorded by both field paramedics and emergency department (ED) physicians. Safety was evaluated by determining the (1) accuracy of paramedic field assessment, (2) appropriateness of field administration of MS, and (3) therapeutic complications. During the study period, paramedics administered MS to 84 patients. In 69 cases paramedic assessment of either ICP and/or PE corresponded to ED physician diagnosis. In five cases paramedics correctly recognized ICP but missed physical findings of PE. In this group the paramedics' assessment was considered inaccurate but the judgement to give MS was considered appropriate. In the remaining 10 cases paramedics identified ICP or PE but the ED physician diagnosed a different condition. These assessments were considered inaccurate and the management inappropriate. Therefore, overall paramedic accuracy was 77% (true rate 73% to 82%, 95% confidence interval); appropriateness of therapy was 88% (true rate 85% to 92%, 95% confidence interval); and the overall complication rate was 6% (true rate 2% to 12%, 95% confidence interval). Complications of respiratory depression or hypotension occurred in only one of the cases in which MS was inappropriately administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736918 TI - Unsuspected heterotopic pregnancy in a woman without risk factors. AB - A 27-year-old woman presented to the emergency department with abdominal pain. One week prior to this she had had an ultrasound which revealed an intrauterine pregnancy (IUP). A second ultrasound performed at our institution revealed an intrauterine pregnancy along with a concomitant ectopic pregnancy which had ruptured. This case emphasizes that coincident pregnancies may occur in women who are without risk of ectopic pregnancy or multiple gestations. In addition, ultrasound must be evaluated fully for heterotopic pregnancy in all women. PMID- 1736919 TI - Anaphylaxis from administration of intravenous thiamine. AB - The routine administration of intravenous thiamine in the emergency department has become widespread. Although anaphylaxis from intravenous thiamine is felt to be uncommon, it can be life threatening. The authors present such a case and review the literature regarding this clinical entity. This case of anaphylactic reaction appears to be the first instance reported since 1946 in the US literature. However a review revealed that cases of anaphylaxis from thiamine have been reported with some regularity in the non-US literature. Given the large number of patients treated without side effects, it seems that thiamine is relatively safe. However, this case illustrates that the assumption that thiamine is a drug with a completely innocuous nature is not totally accurate. PMID- 1736920 TI - Occult fractures of the femoral neck. AB - Occult fractures of the femoral neck can be subtle or even undetectable on plain radiographs. Yet, untreated, the morbidity of this fracture significantly increases. This report discusses the clinical and radiologic findings seen in occult fractures of the femoral neck. It also discusses the role of tomograms, bone scan, computed tomography, and magnetic resonance imaging in further delineating this entity. PMID- 1736921 TI - Neuroimaging of fractureless transforamen magnum penetrating injury of the cerebellum. AB - An unusual case of penetrating injury to the cerebellum by a foreign body is described. The authors recommend plain radiographs and computed tomography to rule out fractures of the skull vault and base and the upper cervical spine, as well as to ascertain the presence and location of foreign bodies. Magnetic resonance imaging is ideal for the follow-up assessment of brain damage. PMID- 1736922 TI - Magnesium deficiency: recognition and treatment in the emergency medicine setting. AB - Magnesium deficiency and its clinical manifestations are common in patients presenting to the emergency department. Assessment of the total body magnesium status of a patient is problematic since the serum magnesium concentration, the only readily available clinical test for this condition, may not be accurate in predicting the intracellular magnesium concentration. Therefore, empiric magnesium therapy should be considered in high-risk patients. Since magnesium participates in numerous metabolic processes in the body, a deficiency can affect multiple organ systems and present clinically in a variety of ways. Magnesium deficiency is reviewed in this paper with regard to therapeutic implications; specific treatment guidelines are given including dose, infusion rate, and magnesium preparation. Magnesium is also reviewed with regard to its homeostasis and metabolic role in the body. Special mention is made regarding precautions for use of magnesium in the setting of renal insufficiency. PMID- 1736923 TI - An analysis of reimbursement for outpatient medical care in an urban hospital emergency department. AB - The investigators examined the demographic and clinical factors associated with the collection experience in a series of 786 patients who were treated in an urban hospital emergency department (ED) but not admitted to the hospital. They found that 57% of the total net charge of $150,489 had been paid within 180 days. This rate can be compared with an average inpatient collection rate of 85% at 180 days. Seven factors were found to account for the collection rate variation, making up 38.4% of the total variation. Age, gender, primary diagnosis, season of visit, time of arrival, and residence were not found to be main contributors. Insufficient collection rates may be an indication that EDs increasingly are becoming a financial risk to hospitals. The hospital's collection experience will become more important as an indicator of financial risk if the costs of operating EDs continue to escalate and collection rates do not improve. Both the costs of providing a service and the amount of the charge actually collected are valid concerns to those operating EDs. PMID- 1736924 TI - Observation medicine: an annotated bibliography. PMID- 1736925 TI - Minor head trauma. PMID- 1736926 TI - Kerr Insta-Char Activated Charcoal Product. PMID- 1736927 TI - Less problems for ears! PMID- 1736928 TI - A gender difference in the association between salt sensitivity and family history of hypertension. AB - We examined 174 subjects (82 men and 92 women) with essential hypertension to determine whether gender played an important role in the association of blood pressure (BP) familial disposition, and hypertension. To evaluate the salt sensitivity of BP, we measured changes in blood pressure after restricting salt intake from about 15 g/day to less than 3 g/day. The familial disposition to hypertension was categorized into four groups according to the presence or absence of hypertension in the father, mother, and siblings. If none, one, two, or three family members had hypertension, they were assigned the FH(-), FH(+), FH(++), and FH( ) groups, respectively. Only in women did the FH(-) group show a significantly smaller blood pressure reduction than that of the other groups. The mean BP reduction in the four groups was 4.1 +/- 1.9, 8.5 +/- 1.1, 10.1 +/- 1.5, and 11.2 +/- 2.8 mm Hg (mean +/- SEM), respectively. This difference in BP reduction was not observed in men. Multiple regression analysis, using percent changes in mean BP as the dependent variable and other factors as independent variables, also showed a significant partial correlation coefficient for familial disposition to hypertension only in women. Thus, the relationship between salt sensitivity and familial disposition to hypertension differed according to gender. This difference may provide an important insight into the hereditary nature of hypertension. PMID- 1736929 TI - Discrepancies in recording systolic blood pressure of elderly persons by ambulatory blood pressure monitor. AB - Agreements between auscultatory blood pressure measurements and recordings of the Suntech Accutracker II ambulatory blood pressure monitor (ABPM) were examined in 103 participants ages 23 through 91 to estimate influence of age on accuracy of automated recordings. Simultaneous auscultation by two technicians and recording by the ABPM were compared. Technicians demonstrated close agreement in auscultation of blood pressure. Mean systolic blood pressure measured by ABPM was 5.6 mm Hg lower and mean ABPM diastolic blood pressure was 6.3 mm Hg lower than average auscultatory blood pressure measured by technicians (P less than .0001). Discrepancies in systolic blood pressure measurements between technicians and ABPM were associated with age and systolic blood pressure. The age effect, controlled for gender and race, was a 0.15 mm Hg increase in systolic blood pressure discrepancy per year of age. Discrepancies in diastolic blood pressure measurements were associated with race but not with age or body size measurements. Automated recordings of blood pressure by this ABPM may have systematic bias compared to auscultation which exceeds current standards for ABPM instrumentation. For systolic blood pressure, this bias increases with age and may affect interpretation of ABPM recordings in elderly persons. PMID- 1736930 TI - Insulin resistance in secondary hypertension. AB - The insulin sensitivity of five essential hypertensive patients was compared to five patients with renovascular hypertension, five patients with primary hyperaldosteronism, and five normotensive subjects, using the euglycemic hyperinsulinemic clamp technique. Essential hypertensive patients had significantly lower insulin sensitivity than patients with hyperaldosteronism and renovascular hypertensive patients (P = .0066, P = .004, respectively). Hyperaldosteronism patients also had less insulin sensitivity than renovascular hypertensive patients (P = .016). A significant negative correlation was found between body mass index and insulin sensitivity index for essential hypertension patients only (r = -0.87, P less than .003). No such correlation was found in the secondary hypertension patients. The findings suggest a causal relationship between insulin resistance and the development of essential hypertension. Secondary hypertension, on the other hand, is not such an insulin resistant state. PMID- 1736931 TI - Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients. AB - To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin angiotensin-aldosterone system. PMID- 1736932 TI - Gender differences in left ventricular structure and function in young adults with normal or marginally elevated blood pressure. AB - Gender differences in left ventricular structure and function were evaluated in 68 male and 69 female young adults (mean age 30 +/- 7 years) with normal or marginally elevated blood pressure. Left ventricular mass index was greater in men than in women, even after controlling for blood pressure. There were no significant gender differences in left ventricular systolic function. Doppler indices of diastolic filling were also similar in men and women. Thus, men have a significantly greater left ventricular mass index than women, but this difference in ventricular size is not associated with differences in systolic or diastolic function. PMID- 1736933 TI - The Trial of Antihypertensive Interventions and Management (TAIM) Study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. AB - The Trial of Antihypertensives Interventions and Management (TAIM) was a multicenter double-blind placebo-controlled clinical trial of drug and diet combinations for the treatment of mild hypertension among 878 participants, ages 21 to 65, 110% to 160% ideal weight, and with baseline diastolic blood pressure 90 to 100 mm Hg. The drugs used were placebo, chlorthalidone (25 mg/daily) or atenolol (50 mg/daily). The diets studied were usual, weight loss, sodium reduction/potassium increase. Trial end points were 6-month diastolic blood pressure change, cardiovascular risk change, and quality of life change. Either drug combined with weight loss produced the greatest blood pressure reduction of 15 mm Hg, compared to 8 mm Hg on placebo/usual diet. Adding sodium restriction to either drug did not enhance blood pressure lowering effect. Drugs outperformed diet in terms of antihypertensive effect. However, those on placebo and assigned to weight reduction who lost more than 4.5 kg and those on sodium restriction who reduced sodium to less than 70 mEq daily lowered blood pressure to a similar extent as those on either of the two drugs alone. Cardiovascular risk at 6 months relative to baseline ranged from 0.85 in weight loss/atenolol subgroup to 1.04 in the usual diet/chlorthalidone subgroup. Blacks were more responsive to chlorthalidone plus weight loss and whites to atenolol plus weight loss. Quality of life, as measured by scales of distress and well-being, was favorably affected by weight reduction. Although there were few side effects of the drugs and most patients improved on most parameters, sexual complaints were worsened among those on chlorthalidone and usual diet compared to placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736934 TI - Difficulties with cytosolic free calcium measurement. Comment on the study by Yokokawa et al. PMID- 1736935 TI - Commentary on the Trial of Antihypertensive Interventions and Management (TAIM) Study. PMID- 1736936 TI - Excess prevalence of extracranial carotid artery lesions in renovascular hypertension. AB - High renin hypertension has been associated with a higher risk of stroke than low to-normal renin hypertension. Accordingly, we investigated prospectively the prevalence of the extracranial carotid artery lesions in a case-control study of 70 patients (38 women and 32 men, aged 16 to 77 years) without history or symptoms of cerebrovascular disease. Renovascular hypertension was diagnosed in 35 patients on the basis of the angiographic demonstration of renal artery stenosis and of the favorable outcome after revascularization. It was caused by atherosclerosis in 20 patients and by fibrodysplasia in 15. Each renovascular hypertensive patient was individually matched with a control with primary hypertension for sex, race, age, blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. Carotid arteries were evaluated by a High Resolution Duplex system (Biosound 2000, probe 4 cm, 8 mHz). Our results show that after the matching the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). In renovascular hypertensives the prevalence of carotid artery lesions (82.6%) was significantly (P less than .01) higher than in primary hypertensives (42.9%). The higher prevalence of lesions in renovascular hypertension was observed not only in patients with atherosclerosis (100% v 55%, P less than .001), but also in those with fibrodysplasia (57% v 27%, P less than .01). Thus, for the same demographic features and overall cardiovascular risk profile, renovascular hypertension carries a more detrimental effect on the carotid artery than primary hypertension. PMID- 1736937 TI - Spatial visualization of the maturing HIV-1 core and its linkage to the envelope. AB - The core of late states of maturing human immunodeficiency virus type 1 (HIV-1) has been visualized in three dimensions at approximately 7 nm resolution by electron microscopic tomography. After budding, approximately 25 nm thick precursor material is observed densely assembled inside the viral envelope. Upon proteolysis the core material is transported and condensed in the center of the virion. The core, 100 nm in length, spans the entire diameter of the virion showing a 40-60 nm wide free end and a narrow end approximately 20 nm. A model of the core is derived consisting of two fibers packed into a bilateral, elongated structure. Two ends of the fibers are compacted together, forming one narrow end of the core, while the two other fiber ends are situated more loosely together allowing for flexibility. Structural maturation of the virus could be reflected by the degree of compactness of the core. The narrow end of the core is observed attached to the envelope with a conspicuous core-envelope link (CEL). PMID- 1736938 TI - Lectin-carbohydrate interactions and infectivity of human immunodeficiency virus type 1 (HIV-1). AB - The aim of this study was to determine whether mannosyl-specific lectins, especially Concanavalin A (ConA), may bridge HIV-1 env glycoproteins to cell membranes to increase virus binding to its targets, and to what extent this lectin-carbohydrate interaction can modify HIV-1 infectivity for monocytic compared with lymphoid cells. Monocytic U937 and lymphoid CEM cells, which both express surface mannose, were utilized. Whether first incubated with env glycoprotein or with the cells, lectins bound both to the cells and to radiolabeled recombinant gp160 (rgp160). Thus, they enhanced rgp160 adsorption to the cells in a methyl-alpha-mannose inhibitable manner. ConA did not appear to bind to the V1 domain of CD4 at the U937 cell surface since Leu3a binding was not blocked in the presence of ConA, nor was recombinant CD4 retained on a ConA agarose affinity matrix. Moreover, enhanced rgp160 binding to the cells was CD4 independent, since it was not modified by preincubating the cells with Leu3a. Finally, ConA did not inhibit the binding of CD4-IgG3 chimeric molecules to virions immobilized on nitrocellulose membrane, which argues against the possibility that it interferes with the interaction of gp120 and CD4. However, both when incubated with the virus or with the cells and despite mediating enhanced binding of env glycoprotein, ConA neutralized HIV-1 infectivity for monocytic U937 as well as for lymphoid CEM cells. In this respect, ConA behaves like neutralizing antibodies which do not interfere with CD4 binding of gp120 but rather with some later event that leads to virus entry. These findings obtained with plant lectins may be of relevance in vivo, inasmuch as endogenous mannosyl binding proteins, which are known to function as opsonins, have been reported to inhibit in vitro infection by HIV-1. PMID- 1736939 TI - Inhibition of HIV production in cells containing an integrated, HIV-regulated diphtheria toxin A chain gene. AB - Construction of a DNA plasmid that expresses a diphtheria toxin A chain (DT-A) gene under control of human immunodeficiency virus (HIV-1) proteins Tat and Rev has been described. Here the generation of HeLa cell clones containing integrated, HIV-regulated DT-A sequences is reported. Five such clones were identified by their decreased expression of a luciferase reporter gene transiently cotransfected with Tat- and Rev-encoding plasmids. The decreased luciferase expression most probably was due to activation of the integrated DT-A gene because higher luciferase activity could be restored by introducing either DT antitoxin or a gene encoding a mutant, DT-resistant elongation factor 2 (the intracellular target for DT-A). Analysis by polymerase chain reaction (PCR) indicated that all clones expressed DT-A encoding RNA. The clones were then transfected with an HIV proviral clone and were tested for HIV production; all five clones demonstrated substantially impaired HIV production compared with parental HeLa cells, as shown by p24 assays of culture supernatants. Our success in generating these cell lines indicates that extremely low basal expression has been achieved in view of the high cellular lethality of DT-A. HIV-regulated expression of DT-A may be applicable as a gene therapy approach for the acquired immune deficiency syndrome (AIDS), to bring about selective suicide of HIV infected cells before production of viral progeny. PMID- 1736940 TI - Distinct populations of human immunodeficiency virus type 1 in blood and cerebrospinal fluid. AB - The nucleotide sequence of the gp41 transmembrane protein coding region of human immunodeficiency virus type 1 (HIV-1) proviral DNA obtained from blood and cerebrospinal fluid (CSF) from 6 individuals was determined by direct sequencing of polymerase chain reaction (PCR)-amplified DNA. The direct sequencing approach was performed to avoid errors introduced by Taq polymerase during the amplification reaction. In 3 of 6 paired samples distinct sequence differences between proviral DNA from blood and CSF, ranging from 0.64% to 1.73%, were detected. The greatest diversity (4.2% different amino acids) was found between paired samples of a patient suffering from AIDS encephalopathy, with most of the differences clustering near the carboxy-terminal end of gp41. The results demonstrate that genetically different populations of HIV-1 may be present in different biological compartments and specific neurotropic HIV variants may exist. PMID- 1736941 TI - Modulation of normal human erythropoietic progenitor cells in long-term liquid cultures after HIV-1 infection. AB - Long-term bone marrow cultures (LTBMC) have been infected by two isolates of human immunodeficiency virus type 1 (HIV-1) (HIV-1 LAV and HIV-1 NDK) at multiplicities of infection ranging from 10(2) to 2.10(6) tissue culture infectious units (TCIU) per 10(6) bone marrow mononuclear cells (BMMNC). These infected cells are nonproducer cells and the viruses can be rescued by coculture with peripheral blood lymphocytes, cord blood lymphocytes, or BMMNC and not by the CEM cell line. HIV-1 clearly is not cytopathic for these cells. Following production and growth of erythroid burst-forming units (BFU-E) and erythroid colony-forming units (CFU-E) for at least 6 weeks after infection with HIV-1 NDK, colony assays displayed a 50% inhibition of BFU-E production during 3 weeks of LTBMC. This was followed by a stimulation phase. On the contrary, HIV-1 LAV induces a 150% stimulation of BFU-E production, followed by 50% inhibition. Production of CFU-E was inhibited by 80-100% with the two isolates of HIV-1 after four weeks of LTBMC. Stimulatory and inhibitory activities were recovered from supernatants of infected LTBMC and lymphoid CEM cell lines, suggesting that HIV-1 induces release of a humoral factor responsible for disruption of hemopoietic progenitor cell production in vitro and consequently for hematologic abnormalities in AIDS patients. PMID- 1736942 TI - Population sequence analysis of a simian immunodeficiency virus (32H reisolate of SIVmac251): a virus stock used for international vaccine studies. AB - The virus structural genes gag and env (both gp120 and gp41 regions) of the 32H isolate of SIVmac251 were amplified using the polymerase chain reaction (PCR). The proviral template used in the PCR was DNA isolated from cells used to prepare several experimental SIV vaccines, which have been tested in simians, and a standard challenge stock of virus, which has been used in international collaborative studies. The PCR products were cloned and the nucleotide sequences of several clones were determined for each gene. From a comparison of the sequences obtained the predominant amino acid sequences of gag and env were predicted and the degree of sequence heterogeneity was determined. Conserved and more variable regions of each protein were identified. The gp120 region of env was more heterogeneous than gag or the transmembrane protein of env (gp41). Within gp120, sequence variability was concentrated to specific regions equivalent to the V1, V2, and, to a lesser extent, the C1 regions identified for human immunodeficiency virus type 1 (HIV-1). In contrast the region equivalent to the hypervariable "V3-loop" of HIV-1 was highly conserved. The implications of the data is discussed in relation to the ability of this virus stock to prepare effective vaccines against SIV. PMID- 1736943 TI - Investigation of human immunodeficiency virus fusion peptides. Analysis of interrelations between their structure and function. AB - The N-terminal region of the human immunodeficiency virus type 1 (HIV-1) gp41 appears to be involved in virus-cell membrane fusion. To study the influence of fusion domain structure on gp41 interaction with artificial lipid membranes, two families of peptides were synthesized. The peptides of the first family starting from the C-terminal Gly-532 of gp160 (BRU isolate) were assembled in a stepwise manner to N-terminus of gp41(Ala-517). These hydrophobic peptides, containing 10 16 amino acid residues (a.a.), were able to form channel-like current fluctuation through planar lipid membranes, and the longest 15-16 a.a. peptides lysed the liposomes. Peptides of the second family beginning from the C-terminal Arg-538 and continuing to Val-510 contained several hydrophilic amino acid residues. These 15-22 a.a. peptides also increased the conductance of planar lipid bilayers and lysed liposomes. The degree of liposome lysis depended upon peptide length and concentration. The attachment of gp120 C-terminal amino acid or peptides to N terminus of 517-538 peptide resulted in complete loss of activity. The effects of the second family of peptides on membranes were reduced to a great extent at acidic pH. The conjugation of 22 a.a. Lys peptide with bovine serum albumin decreased its lytic activity. The circular dichroism study of these peptides revealed alpha-helix configuration in hydrophobic and aqueous media only for deca and longer peptides. The electron microscopy of 22 a.a. peptide performed in the aqueous medium showed large spherical aggregates about 0.5-0.7 micron in diameter consisting of long filaments approximately 5 nm in diameter. Other tested peptides could generate only short strings. Thus, the effects of fusion peptides on lipid membranes depends on their sequence and length, secondary and tertiary structures, and freedom of their N-terminus. PMID- 1736944 TI - NdYAG laser treatment of dentinal hypersensitivity. AB - Eighteen per cent of all patients have some degree of sensitivity and a range of therapies has been devised to alleviate this condition. An electronic monitoring machine was constructed which allowed for air stream, directed at a patient's tooth, to be started by the clinician and halted by the patient when the sensation of pain in the tooth became too unpleasant to tolerate. The time for which the patient could tolerate the air flow was electronically measured in units of 1/50th second. By measuring the patient's reaction time on each visit and correcting the readings obtained for 'tooth pain time' using these figures, a quantitative measure of sensitivity change is achieved. Using this system, a clinical trial has been conducted to test the efficacy of the NdYAG dental laser. The 30 patients treated had an average tooth pain time initially of 1.2 seconds. Following laser treatment patients were recalled at 3, 7 and 14 days. At the 2 week review, this figure had increased to 7.8 seconds, which was found to be statistically significant. Control (unlased) teeth demonstrated an average improvement of only 1.7 seconds (not statistically significant). Patients' subjective assessment of sensitivity pain on a 0-10 scale averaged 8.0 before treatment. This reduced to 3.7 after treatment. Treatment of this condition can thus be performed easily and painlessly with a predictable response and considerable patient satisfaction. PMID- 1736945 TI - An investigation of replantation of traumatically avulsed permanent incisor teeth. AB - The success of treatment of 46 replanted, avulsed permanent incisors in 36 children was investigated in relation to some of the factors which have been reported to affect prognosis. Treatment was considered to have been successful if the tooth was still present in the mouth and required no further treatment. If more treatment was necessary, the outcome was considered to be uncertain, while if the tooth had been lost a failure was recorded. Treatment was considered to be successful for 21 teeth, uncertain for 20 teeth and a failure for 5 teeth. A significant relationship was found between success and the method of storing the avulsed tooth, with milk, saliva or saline being the best media. No relationship was demonstrated between the time the avulsed tooth was out of the mouth and success. Root resorption was the most frequent complication of replantation and occurred in 24 teeth. However, no significant relationship between resorption and the time that the avulsed tooth was out of the mouth was demonstrated. PMID- 1736946 TI - Multifocal hairy leukoplakia associated with Kaposi's sarcoma. AB - An HIV-seropositive patient presented with multifocal lesions of both hairy leukoplakia and Kaposi's sarcoma, hairy leukoplakia being present in the epithelium covering the Kaposi's sarcoma lesions. The findings suggest that hairy leukoplakia in immunocompromised patients is both more common and more widely distributed than is generally recognised. PMID- 1736947 TI - 'Proper words in proper places'. PMID- 1736948 TI - The medical arts. AB - There were 152 entries for the Medical Arts Society's annual exhibition and all were shown at the Westminster Gallery, London on October 14-19, last year. The show displayed an exhibition of skill in the mediums of painting, printmaking, sculpture and drawing and prizes were awarded on merit. PMID- 1736949 TI - 'Computers in dentistry'. PMID- 1736950 TI - 'Computers in dentistry'. PMID- 1736951 TI - 'An urgent remedy needed'. PMID- 1736952 TI - Sugar intake and dental caries. PMID- 1736953 TI - 'Management of fissure caries'. PMID- 1736954 TI - Post-smallpox eradication policies. PMID- 1736955 TI - Expanded programme on immunization. Global Advisory Group--Part I. PMID- 1736956 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 1 January 1992. PMID- 1736957 TI - Expanded programme on immunization. Global Advisory Group--Part II. PMID- 1736958 TI - Tobacco or health. Smoking as a cause of cancer. PMID- 1736959 TI - Influenza. PMID- 1736960 TI - Application of multivariate analyses of enzymic data to classification of members of the Actinobacillus-Haemophilus-Pasteurella group. AB - Outer membrane vesicles and fragments from Actinobacillus actinomycetemcomitans, Actinobacillus lignieresii, Actinobacillus ureae, Haemophilus aphrophilus, Haemophilus paraphrophilus, Haemophilus influenzae, Haemophilus parainfluenzae, Pasteurella haemolytica, and Pasteurella multocida were isolated and examined semiquantitatively for 19 enzyme activities by using the API ZYM micromethod. The enzyme contents of vesicles and fragments were compared with the enzyme contents of whole cells of the same organisms. Enzymic data were analyzed by using principal-component analysis and soft independent modeling of class analogy. This technique allowed us to distinguish among the closely related organisms A. actinomycetemcomitans, H. aphrophilus, and H. paraphrophilus. A. actinomycetemcomitans was divided into two groups of strains. A. lignieresii fell outside or on the border of the A. actinobacillus class. A. ureae, H. influenzae, H. parainfluenzae, P. haemolytica, and P. multocida fell outside the A. actinomycetemcomitans, H. aphrophilus, and H. paraphrophilus classes. PMID- 1736961 TI - Antigenic and genomic relatedness among Ehrlichia risticii, Ehrlichia sennetsu, and Ehrlichia canis. AB - Antigenic and genomic relatedness among Ehrlichia risticii, E. sennetsu, and E. canis was analyzed by enzyme-linked immunosorbent assay, Western blotting (immunoblotting) and DNA-DNA hybridization. E. risticii and E. sennetsu were serologically related, and their Western blot antigen profiles were nearly identical. Two antigens of E. sennetsu corresponding to the 28- and 51-kDa antigens of E. risticii were apparently larger than the E. risticii antigens, and the 55-kDa antigen of E. risticii appeared to be unique to this species. The 110 , 70-, and 44-kDa antigens of these two species were identical, as determined by the use of monospecific antibodies. DNA homology between these two species was high. On the other hand, E. canis was antigenically least reactive with the antisera to E. risticii and E. sennetsu. However, a dog convalescent-stage E. canis antiserum recognized antigens in the other two species which were different from those recognized by their homologous antisera. Similarly, homology between the DNA of E. canis and the DNAs of the other two species was very minimal. These results indicate that E. risticii and E. sennetsu are closely related both at the genomic and antigenic levels and that the relationship of these two species with E. canis is minimal. PMID- 1736962 TI - Electrophoretic heterogeneity of ribosomal protein AT-L30 among actinomycete genera. AB - The ribosomal proteins from 17 type strains of species belonging to various actinomycete genera were compared by two-dimensional polyacrylamide gel electrophoresis. I detected a striking variability among certain ribosomal proteins (designated AT-L30 proteins) with respect to electrophoretic mobility in the first dimension. In contrast, such variability was not observed among ribosomal L30 proteins from other bacteria, such as Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Although actinomycete AT-L30 proteins from different taxa exhibited considerable heterogeneity in electrophoretic mobility, within each genus the proteins had a specific mobility characteristic. On the basis of this observation, the ribosomal AT-L30 proteins from 11 type strains of species belonging to the mycolic acid containing genera Nocardia, Rhodococcus, Gordona, and Tsukamurella were analyzed. The relative electrophoretic mobilities of AT-L30 protein preparations from these strains, as determined by two-dimensional gel electrophoresis, revealed that the genera Nocardia, Rhodococcus, Gordona, and Tsukamurella can be sharply separated from each other. My results are consistent with the previously discussed view that each of these genera merits separate genus status. PMID- 1736963 TI - Polyacrylamide gel electrophoresis analysis of ribosomal protein AT-L30 from an actinomycete genus, Streptosporangium. AB - We analyzed the ribosomal AT-L30 proteins from 11 type strains of species belonging to the genus Streptosporangium. The electrophoretic mobilities of the AT-L30 preparations from these strains, as determined by two-dimensional polyacrylamide gel electrophoresis, revealed that they could be divided into three groups. The first group contained Streptosporangium viridogriseum, S. viridogriseum subsp. kofuense, and S. albidum, while the second group contained S. roseum, S. album, S. vulgare, S. nondiastaticum, S. fragile, S. violaceochromogenes, and S. amethystogenes. S. corrugatum was a member of the third group. These groups were completely consistent with Nonomura's previous classification, which was based on morphological criteria. The results of partial amino acid sequencing of AT-L30 preparations from several representative strains strongly supported the hypothesis that each of the three groups of the genus Streptosporangium merits separate generic status. PMID- 1736964 TI - Assignment of Listeria grayi and Listeria murrayi to a single species, Listeria grayi, with a revised description of Listeria grayi. AB - The genomic relatedness between Listeria grayi and Listeria murrayi was reevaluated by using DNA-DNA hybridization, multilocus enzyme electrophoresis, and rRNA restriction fragment length polymorphism techniques. The high levels of similarity observed between the strains of these two species confirmed the data published since 1973 and indicated that they should be considered members of a single species. On grounds of priority, the species should be named L. grayi. PMID- 1736965 TI - Classification of coryneform bacteria associated with human urinary tract infection (group D2) as Corynebacterium urealyticum sp. nov. AB - Urealytic strains of coryneform bacteria that are designated Corynebacterium group D2 and are isolated from human urine are a cause of urinary tract infections. Cell wall and lipid analyses confirmed that these organisms are members of the genus Corynebacterium but can be separated from other species in the genus on the basis of DNA base composition and DNA-DNA hybridization values. Biochemically, strains in this taxon can be distinguished from other Corynebacterium spp. by their failure to produce acid from carbohydrates, by their failure to reduce nitrates, and by their ability to hydrolyze urea. We regard these bacteria as a new species of the genus Corynebacterium and propose the name Corynebacterium urealyticum. The type strain is strain NCTC 12011 (= ATCC 43042). PMID- 1736966 TI - Proposal to change the genus designation Serpula to Serpulina gen. nov. containing the species Serpulina hyodysenteriae comb. nov. and Serpulina innocens comb. nov. AB - The bacterial genus Serpula Stanton et al. 1991 is illegitimate due to the existence of a fungal genus Serpula Pers. ex S. F. Gray. Consequently, a new genus designation, Serpulina, is proposed for this spirochete genus. Serpula hyodysenteriae, the type species, and Serpula innocens Stanton et al. 1991, therefore, become Serpulina hyodysenteriae comb. nov. and Serpulina innocens comb. nov. PMID- 1736967 TI - Validation of the publication of new names and new combinations previously effectively published outside the IJSB. List No. 40. PMID- 1736968 TI - Notification that new names and new combinations have appeared in the IJSB. PMID- 1736969 TI - Helicobacter muridarum sp. nov., a microaerophilic helical bacterium with a novel ultrastructure isolated from the intestinal mucosa of rodents. AB - Helical organisms with novel ultrastructural characteristics were isolated from the intestinal mucosa of rats and mice. These bacteria were characterized by the presence of 9 to 11 periplasmic fibers which appeared as concentric helical ridges on the surface of each cell. The cells were motile with a rapid corkscrewlike motion and had bipolar tufts of 10 to 14 sheathed flagella. The bacteria were microaerophilic, nutritionally fastidious, and physiologically similar to Helicobacter species and Wolinella succinogenes but could be differentiated from these organisms by their unique cellular ultrastructure. Using 16S rRNA sequencing, we found that strain ST1T (T = type strain) was related to previously described Helicobacter species, "Flexispira rappini," and W. succinogenes. The closest relatives of strain ST1T were Helicobacter mustelae and "F. rappini" (average similarity value, 96%). On the basis of phylogenetic data, strain ST1T (= ATCC 49282T) represents a new species of the genus Helicobacter, for which we propose the name Helicobacter muridarum. PMID- 1736970 TI - Analysis of bacteriolytic activity patterns, a novel approach to the taxonomy of enterococci. AB - The bacteriolytic activities of different group D streptococcal species on various media and substrates were studied. Our results showed that all of the enterococcal species which we tested had bacteriolytic activity on at least one of the media used, while the group D nonenterococcal species had no such activity. In addition, using culture media containing different additives and different pH values, we defined seven major groups of bacteriolytic activity (lyogroups), each of which overlapped with one species (four lyogroups), two species (two lyogroups), or four species (one lyogroup). The detection of enterococcal lyogroups proved to be as reliable for species identification as the conventional methods presently in use. PMID- 1736971 TI - Taxonomic study of the genus Brachybacterium: Brachybacterium nesterenkovii sp. nov. AB - A new species, Brachybacterium nesterenkovii, is proposed for a group of coryneform bacteria that were isolated from milk products. These organisms have morphological, biochemical, and chemotaxonomic characteristics that are peculiar to the genus Brachybacterium. In contrast to strains of the only previously described species of the genus, Brachybacterium faecium, the representatives of the new species lack glycine in their peptidoglycan, although the peptidoglycan is of the same general type, and have large amounts of rhamnose in their cells. The strains of B. nesterenkovii exhibit no serological relationship with strains of B. faecium; in a numerical phenotypic analysis the two species were easily separated and formed clear-cut clusters. DNA-DNA hybridization between the type strains of B. faecium and B. nesterenkovii showed a level of homology of 22%. Strain 35 (= IMV Ac-752) is the type strain of B. nesterenkovii. PMID- 1736972 TI - Ambulatory chemotherapy. PMID- 1736973 TI - The value of magnetic resonance imaging in assessment of carcinoma of the cervix and its response to radiotherapy. PMID- 1736974 TI - Local and systemic eosinophilia in patients with carcinoma of the uterine cervix undergoing radiation therapy: correlation with radiation response. AB - Forty-nine patients with squamous carcinoma of the uterine cervix undergoing supervoltage 60Co radiotherapy were investigated to determine the significance of quantitation of eosinophils in the tumour tissue as well as in blood. The blood absolute eosinophil count (AEC) at presentation was higher in patients with Stages III and IV disease (0.52 +/- 0.09 x 10(9)/l, mean +/- SEM) when compared with early stages (Stages I and II, 0.35 +/- 0.07 x 10(9)/l). Forty-four patients (90%) showed a steady rise in AEC during the course of therapy. The patients showing good radiation response (n = 13, greater than or equal to 50% regression), displayed a more pronounced rise in AEC during the course of radiotherapy (0.66 +/- 0.24 x 10(9)/l) and had more eosinophils in the tumour tissue (7.4 +/- 0.66/oil immersion field) than the poor responders (n = 36, less than 50% regression, rise in eosinophil count 0.22 +/- 0.04 x 10(9)/l, eosinophils in tumour tissue 2.9 +/- 0.55/oil emersion field, P less than 0.0001 for both parameters). We conclude that quantitation of eosinophils in blood and tumour tissue before and during radiotherapy in patients with squamous carcinoma of the uterine cervix is useful in predicting radiation response. PMID- 1736975 TI - Histiocytosis X: does radiotherapy still have a role? AB - Seventeen cases of histiocytosis X are presented (11 children and 6 young adults, with the usual male predominance), having a minimum follow-up of 1 year and a maximum of 20 years. In these age groups, even small doses of radiation should not be given without careful consideration, but fairly low doses carry only a small risk and may be very useful in management. Unlike chemotherapy, radiotherapy can be confined to the affected area, or to the area causing symptoms. All but two of our patients had radiotherapy for bone deposits; only one failed to show a complete response. In addition, the diabetes insipidus of two children responded immediately to radiation of the pituitary. One patient, however, after responding well to radiation for bone deposits, suffered increasing symptoms due to lung involvement and the latter showed no response. This striking contrast in radiosensitivity is hard to explain, given the identical histology obtained by biopsy from each site, but it has been noted many times by others. PMID- 1736976 TI - Intra-arterial adriamycin, conventionally fractionated radiotherapy and conservative surgery for soft tissue sarcomas. AB - Thirteen patients with soft tissue sarcomas were treated with a combination of intra-arterial Adriamycin, conventionally fractionated radiotherapy (2 Gy per day), and conservative surgery (trimodal therapy). Severe acute complications occurred in 10 patients: 3 brachial artery thromboses, 6 delayed wound healing, 4 wound infections, and 3 cases of necrosis of the skin plus subcutaneous tissues. Three patients have developed local recurrence. Five patients are alive, 4 of whom are disease-free, and the median follow up time of surviving patients is 56 months. One has significant impairment of limb function due to joint ankylosis. An additional 2 patients were treated with intra-arterial Adriamycin and conservative surgery for local recurrence after previous surgery and radiotherapy; both died of subsequent metastatic disease, one having a further local recurrence. One patient with multifocal angiosarcoma was treated with intra arterial Adriamycin and radiotherapy but no surgery, and is alive free of disease 49 months later. The combination of radiotherapy and intra-arterial Adriamycin with surgery resulted in significant acute toxicity. This small study has not demonstrated any improvement in local control compared with that expected with conservative surgery and radiotherapy alone. PMID- 1736977 TI - Preoperative radiotherapy for initially inoperable extremity soft tissue sarcomas. AB - The results and complications of a combination of preoperative radiotherapy and surgery in the treatment of 70 patients with large or fixed extremity soft tissue sarcomas are reported. Sixty-one patients were referred with a primary tumour and 9 had recurrences. Thirty-three patients had tumours in the thigh and 38 tumours were fixed to neighbouring structures. The mean preoperative dose was 53 Gy (range 21-75). Eleven patients received a postoperative boost to tumour site. Four patients received preoperative intra-arterial Adriamycin. Overall, 42 patients (60%) responded to the radiotherapy, 4 with complete tumour resolution. Eighty per cent of those receiving greater than or equal to 60 Gy responded and a significant correlation between 2 Gy equivalent dose and response was demonstrated (P less than 0.005). The degree of tumour necrosis was increased in 23 of 52 evaluable patients following radiotherapy, although there was no correlation with dose or clinical response. There have been eight local recurrences and 17 deaths after a median follow-up of 2 years. Tumour size less than 10 cm was the only significant factor in the development of local recurrence (P = 0.04). Thirty-six patients developed immediate postoperative complications: 9 major (13%), 13 moderate (19%) and 14 minor (20%). Increasing patient age was the only significant independent factor for the development of complications (P = 0.015). Preoperative radiotherapy will usually permit limb conservation of extremity sarcomas which otherwise would be inoperable or require amputation. However, the increased incidence of wound complications in older patients demands meticulous technique. PMID- 1736978 TI - Growth hormone and breast cancer. PMID- 1736979 TI - Treatment of lower limb basal cell and squamous cell carcinomas with radiotherapy. AB - In order to evaluate the role of photon based radiotherapy regimens in the treatment of lower limb basal cell and squamous carcinomas, a retrospective analysis of the results of X-ray treatment to 65 such lesions in 60 patients was made. The mean age was 73.3 years, with a range of between 46 and 93 years. Seventy-seven per cent (46/60) of the patients were female. The overall recurrence rate was 4.6% (3/65), and the radionecrosis rate was 9.2% (6/65), with no significant bias in terms of sex or laterality. For regimens giving an NSD of between 1700 rets and 1850 rets to a surface area of less than 30 cm2, the risk of treatment failure was less than 6%. PMID- 1736980 TI - Improving communication with oncology patients: taping the consultation. AB - Patients are often dissatisfied with the information provided for them by doctors. A simple cheap method of improving communication by tape recording the initial consultation with oncology outpatients is described. Analysis of 100 taped consultations by a subsequent questionnaire revealed that patients and their relatives claimed enormous benefit from the opportunity to hear the consultation again. PMID- 1736981 TI - Selection of young women with high-risk breast cancer for adjuvant systemic therapy. AB - Biological criteria of tumour aggressiveness have recently been recommended for use in selecting high-risk cases for adjuvant systemic therapy after primary treatment of breast cancer. Without them, the clinician has considerable difficulty in balancing the morbidity of cytotoxic therapy against the possible benefits. Consistent evidence that patients under the age of 35 years have the worst prognosis of all age groups, while those in the 45-49 age group have the best prognosis, should help in a decision on suitable adjuvant treatment for either node-positive or node-negative young women with breast cancer. PMID- 1736982 TI - Seminoma or sarcoid? AB - A 33-year-old man subsequently diagnosed as having sarcoidosis presented with the clinical features of a testicular tumour with metastatic spread to para-aortic lymph nodes. Histological examination of the testis and para-aortic lymph node biopsy showed florid granulomatous change and a Kveim test was positive. This is a previously unreported presentation of sarcoidosis and emphasizes that histological confirmation of malignancy is essential prior to institution of cytotoxic therapy. PMID- 1736983 TI - Breast metastases to bones of the extremities: simultaneous involvement of all four limbs. AB - Metastases to bones of the hands and feet are unusual, and simultaneous metastases to the bones of more than one extremity in a given patient is an extremely rare occurrence with only five previous case reports. In each of these cases the bones of two extremities were affected. A case is presented where the bones of both hands and both feet exhibited bone metastases. A second case with foot bone metastases is recorded. In both cases the primary tumour was a breast carcinoma. Theories of causation of such metastases are discussed. PMID- 1736984 TI - Intermittent superior vena cava syndrome caused by a Hickman catheter. AB - A case of intermittent superior vena cava syndrome caused by a Hickman catheter is reported. The symptoms resolved on removal of the catheter. The use of anticoagulants in conjunction with indwelling venous catheters is discussed. PMID- 1736985 TI - Dramatic response of recurrent invasive thymoma to high doses of corticosteroids. AB - We report the case of a widely invasive thymoma non-associated with myasthenia gravis which responded only to high doses of corticosteroids. We review the other few reported cases of complete response achieved by this treatment and we stress the possible use of high doses of corticosteroids in the management of recurrent invasive thymoma. PMID- 1736986 TI - The disulfide bonds in antibody variable domains: effects on stability, folding in vitro, and functional expression in Escherichia coli. AB - The formation of the disulfide bonds in the variable domains VH and VL of the antibody McPC603 was found to be essential for the stability of all antigen binding fragments investigated. Exposure of the Fv fragment to reducing conditions in vitro resulted in irreversible denaturation of both VH and VL. In vitro refolding of the reduced Fv fragment was only possible when the disulfide bonds were allowed to form under oxidizing conditions. The analysis of a series of mutants of the Fv fragment, the Fab fragment and the single-chain Fv fragment, all secreted into the periplasm of Escherichia coli, in which each of the cysteine residues of the variable domains was replaced by a series of other amino acids, showed that functional antigen binding fragments required the presence of both the disulfide bond in VH and the one in VL. These results were also used to devise an alternative expression system based on the production of insoluble fusion proteins consisting of truncated beta-galactosidase and antibody domains, enzymatic cleavage, and refolding and assembly in vitro. This strategy should be useful for providing access to unstable antibody domains and fragments. PMID- 1736987 TI - Conformational isomerism of endothelin in acidic aqueous media: a quantitative NOESY analysis. AB - The conformational features of endothelin-1 (ET-1) in mixed water/ethylene glycol media have been studied by two-dimensional 1H NMR experiments throughout the pH range 3.2-7.2. At pH less than 5 all backbone NH signals can be observed, and NOESY experiments provided a large set of dipolar cross-peaks. Cross-peak intensities from each experiment (different mixing times and H2O versus D2O) were converted to distance constraints using a novel algorithm (program DISCON) for removing spin diffusion effects and thus obtain cross-rates rather than cross peak intensities. A set of 168 nonstereospecific distance bounds (average experimental precision, +/- 0.38 A) was used in dynamics simulated annealing refinements. Two consensus structural features were found--a reverse turn at Ser5 ---Asp8 and an alpha-helical stretch from Lys9 to Cys15; however, after constraint-free minimization, structures generated using XPLOR-1.5, CONGEN, and DISCOVER all violated at least 32% of the bounds by more than 0.2 A, which we ascribe to conformational isomerism. When the constraints were modified to reflect subsequent experimental data and to eliminate constraints that could not be obeyed by any single conformer structure, the relaxed structures still violated at least 15% of this more limited and looser set of constraints. Therefore, a modified procedure for constrained dynamics refinement (using XPLOR 2.1), which allows for conformational isomerism outside of the central helical core region, was developed. This "conformer search procedure" produced structures which fell into five tightly defined conformational clusters. The two most populated clusters correspond to a rotation of the 8,9-amide unit. The conformer which we propose as the major contributor at pH 3.2-5.8 was defined to a backbone rmsd of 0.51 A over residues 1----15. An alternative description of the motional averaging in segments of the endothelin structure as extensive randomization rather than rapid interconversion between a small number of discreet conformers was ruled out by an analysis of NH shift-temperature gradients and exchange rates. This analysis suggests that small delta delta/delta T values need not correlate with H-bonding for conformational mixtures. In ET-1 the greatest motional averaging occurs from Ser2 through Ser5 (not in the C-terminus) and may be so extensive as to approximate a flexible random coil population as high as 30%. The C-terminus shows less rapid and less extensive conformational averaging, but no definitive structures for individual conformers could be derived in the absence of stereospecific constraints. The pharmacological implications of the consensus structural features are discussed. PMID- 1736988 TI - Spectroscopic evidence for an intermediate in the T6 to R6 allosteric transition of the Co(II)-substituted insulin hexamer. AB - The phenol-induced conformational transition in the insulin hexamer is known to involve a large change in structure wherein residues 1-8 of the insulin B-chain are transformed from an extended coil (T-state) to a helix (R-state). This change in protein conformation both exposes a cryptic protein pocket on each subunit to which phenol binds and forces the HisB10 zinc sites to undergo a change in coordination geometry from octahedral to tetrahedral [Derewenda, U., Derewenda, Z., Dodson, E. J., Dodson, G. G., Reynolds, C. D., Smith, G. D., Sparks, C., & Swensen, D. (1989) Nature 338, 593-596]. Substitution of Co(II) for Zn(II) at the HisB10 sites introduces a sensitive chromophoric probe of the structural and chemical events that occur during this allosteric transition [Roy, M., Brader, M. L., Lee, R. W.-K., Kaarsholm, N. C., Hansen, J. F., & Dunn, M. F. (1989) J. Biol. Chem. 264, 19081-19085]. In this study, using rapid-scannig stopped-flow (RSSF) UV-visible spectroscopic studies, we demonstrate that a transient chemical intermediate is formed during the phenol-induced conversion of Co(II)-substituted hexamer from the T-state to the R-state. Decomposition of the RSSF spectra gave a spectrum for the intermediate with d-d transitions consistent with the assignment of the intermediate as either a distorted tetrahedral or a 5-coordinate Co(II) species. Possible structures for the intermediate and the implications of these findings to the allosteric mechanism are considered. PMID- 1736989 TI - Fluorescence, CD, attenuated total reflectance (ATR) FTIR, and 13C NMR characterization of the structure and dynamics of synthetic melittin and melittin analogues in lipid environments. AB - The structure and dynamics of synthetic melittin (MLT) and MLT analogues bound to monomyristoylphosphatidylcholine micelles, dimyristoylphosphatidylcholine vesicles, and diacylphosphatidylcholine films have been investigated by fluorescence, CD, attenuated total reflectance (ATR) FTIR, and 13C NMR spectroscopy. All of these methods provide information about peptide secondary structure and/or about the environment of the single tryptophan side chain in these lipid environments. ATR-FTIR data provide additional information about the orientation of helical peptide segments with respect to the bilayer plane. Steady state fluorescence anisotropy, fluorescence lifetime, and 13C NMR relaxation data are used in concert to provide quantitative information about the dynamics of a single 13C-labeled tryptophan side chain at position 19 in lipid-bound MLT, and at positions 17, 11, and 9, respectively, in lipid-bound MLT analogues. Peptide chain dynamics are probed by NMR relaxation studies of 13C alpha-labeled glycine incorporated into each of the MLT peptides at position 12. The cumulative structural and dynamic data are consistent with a model wherein the N-terminal alpha-helical segment of these peptides is oriented perpendicular to the bilayer plane. Correlation times for the lysolipid-peptide complexes provide evidence for binding of a single peptide monomer per micelle. A model for the membranolytic action of MLT and MLT-like peptides is proposed. PMID- 1736990 TI - Light-induced charge separation in Rhodopseudomonas viridis reaction centers monitored by Fourier-transform infrared difference spectroscopy: the quinone vibrations. AB - Static FTIR light-induced difference spectra have been recorded for reaction centers from Rhodopseudomonas viridis in the following charge-separated states: P+QA(-)-PQA, P+QB(-)-PQB, I(-)-I, I-QA(-)-IQA, and I-QA(2-)-IQA. A comparison of the I(-)-I difference spectra with the I-QA(-)-IQA difference spectra reveals new bands which can be assigned to QA- vibrations; these vibrations are also observed in the P+QA(-)-PQA and P+QB(-)-PQB difference spectra. Through an analysis of all of the static difference spectra, the electron-transfer pathway can be monitored in the infrared from the primary donor, P, to the secondary acceptor, QB, via the intermediate acceptor, I, and the primary acceptor, QA. The difference spectra are dominated by absorbance changes of prosthetic groups, with very few identifiable contributions from amino acids and little overall structural change in the protein backbone, involving only one or two residues for the various charge-separated states. Oxidation of the primary donor in the reaction center shows the characteristic absorbance changes of the 9-keto and 10-ester carbonyl groups observed upon oxidation of bacteriochlorophyll b in a non-hydrogen-bonded environment [Ballschmiter, K. H., & Katz, J. J. (1969) J. Am. Chem. Soc. 91, 2661 2677]. Reduction of the quinones in the reaction center yields absorbance changes of the carbonyls observed during reduction of quinones in a hydrogen-bonded environment [Bauscher, M., Nabedryk, E., Bagley, K., Breton, J., & Mantele, W. (1990) FEBS Lett. 261, 191-195].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736991 TI - A 31P NMR study of mitochondrial inorganic phosphate visibility: effects of Ca2+, Mn2+, and the pH gradient. AB - The effects of external pH, temperature, and Ca2+ and Mn2+ concentrations on the compartmentation and NMR visibility of inorganic phosphate (Pi) were studied in isolated rat liver mitochondria respiring on succinate and glutamate. Mitochondrial matrix Pi is totally visible by NMR at 8 degrees C and at low external concentrations of Pi. However, when the external Pi concentration is increased above 7 mM, the pH gradient decreases, the amount of matrix Pi increases, and the fraction not observed by NMR increases. Raising the temperature to 25 degrees C also decreases the pH gradient and the Pi fraction observed by NMR. At physiologically relevant concentrations, Ca2+ and Mn2+ do not seem to play a major role in matrix Pi NMR invisibility. For Ca2+ concentrations above 30 nmol/mg of protein, formation of insoluble complexes will cause loss of Pi signal intensity. For Mn2+ concentrations above 2 nmol/mg of protein, the Pi peak can be broadened sufficiently to preclude detection of a high-resolution signal. The results indicate that mitochondrial matrix Pi should be mostly observable up to 25 degrees C by high-resolution NMR. While the exact nature of the NMR-invisible phosphate in perfused or in vivo liver is yet to be determined, better success at detecting and resolving both Pi pools by NMR is indicated at high field, low temperature, and optimized pulsing conditions. PMID- 1736992 TI - X-ray diffraction reconstruction of the inverted hexagonal (HII) phase in lipid water systems. AB - The structure of the inverted hexagonal (HII) phase in biological lipid-water systems is studied to examine the physical interactions which drive the polymorphic phase behavior and which are also thought to play a relevant role in biological membrane function. A method is derived which yields the complex phase factors of the HII phase diffraction amplitudes from examination of a single sample. This method is applied to a low-resolution Fourier reconstruction of the HII phase in dioleoylphosphatidylethanolamine (DOPE) + water, specifically to examine deviations from the presumed circular model of the HII phase. It is found that the average radius of the water core, Rw, as determined from a Fourier reconstruction, is in good agreement with previously measured values of Rw obtained from more time-consuming traditional methods [Tate, M. W., & Gruner, S. M. (1989) Biochemistry 28, 4245]. In addition to the average value of Rw, the Fourier reconstruction also can be used to determine the true shape of the water core. It is found that the water core is circular to within 5% of Rw when the unit cell size is less than approximately 75 A. Above 75 A, however, a definite shape deformation becomes apparent, with radial noncircularities of 5-10%, probably in response to the increased entropic cost of packing the hydrocarbon chains into the anisotropic environment of the HII unit cell [Kirk, G. L., Gruner, S. M., & Stein D. E. (1984) Biochemistry 23, 1093]. As a more direct probe of the packing anisotropy, Fourier reconstructions of DOPE + dodecane and DOPE + squalene systems were compared with the reconstruction of DOPE. These oils are known to promote the low temperature occurrence of the HII phase, presumably by a reduction in the hydrocarbon packing stress. In support of this hypothesis, the alkanes were observed to relax the water core to a circular shape for even large lattices. In addition, anisotropy of the electron density near the end of the lipid chains is reduced when alkane is added, implying a more uniform hydrocarbon packing environment, consistent with the results of neutron diffraction upon the addition of deuterated decane [Turner, D. C., Gruner, S. M., & Huang, J. (1992) Biochemistry (following paper in this issue)]. PMID- 1736993 TI - Distribution of decane within the unit cell of the inverted hexagonal (HII) phase of lipid-water-decane systems determined by neutron diffraction. AB - The addition of a free alkane such as decane to lipid-water systems is known to promote the formation of a low-temperature inverted hexagonal (HII) phase [Kirk, G. L., & Gruner, S. M. (1985) J. Phys. (Paris) 46, 761]. Kirk et al. [Kirk, G. L., Gruner, S. M., & Stein, D. E. (1984) Biochemistry 23, 1093] have discussed the hydrocarbon packing anisotropy in the HII unit cell and have suggested that free alkane will distribute in a way that reduces this packing anisotropy by allowing the lipid chain environment to become more uniform. By combining neutron and X-ray diffraction data to do a Fourier reconstruction of the HII phase of dioleoylphosphatidylethanolamine (DOPE) + water + deuterated decane, it was found that the decane preferentially partitions into the interstitial regions of the HII unit cell where it should be the most effective in alleviating the hydrocarbon chain packing stress, supporting the suggestion of Kirk et al. Using the distribution of decane within the unit cell, we have calculated the lipid length distribution for the situations with and without added alkane. With a suitable molecular model, this lipid length distribution may eventually be used to calculate the free energy change upon the addition of alkane. Such a measurement is important for a more realistic understanding of the interactions which lead to the formation of the HII phase. PMID- 1736994 TI - Substitution of Torpedo acetylcholine receptor alpha 1-subunit residues with snake alpha 1- and rat nerve alpha 3-subunit residues in recombinant fusion proteins: effect on alpha-bungarotoxin binding. AB - A fusion protein consisting of the TrpE protein and residues 166-211 of the Torpedo acetylcholine receptor alpha 1 subunit was produced in Escherichia coli using a pATH10 expression vector. Residues in the Torpedo sequence were changed by means of oligonucleotide-directed mutagenesis to residues present in snake alpha 1 subunit and rat nerve alpha 3 subunit which do not bind alpha bungarotoxin. The fusion protein of the Torpedo sequence bound 125I-alpha bungarotoxin with high affinity (IC50 = 2.5 x 10(-8) M from competition with unlabeled toxin, KD = 2.3 x 10(-8) M from equilibrium saturation binding data). Mutation of three Torpedo residues to snake residues, W184F, K185W, and W187S, had no effect on binding. Conversion of two additional Torpedo residues to snake, T191S and P194L, reduced alpha-bungarotoxin binding to undetectable levels. The P194L mutation alone abolished toxin binding. Mutation of three Torpedo alpha 1 residues to neuronal alpha 3-subunit residues, W187E, Y189K, and T191N, also abolished detectable alpha-bungarotoxin binding. Conversion of Try-189 to Asn which is present in the snake sequence (Y189N) abolished toxin binding. It is concluded that in the sequence of the alpha subunit of Torpedo encompassing Cys 192 and Cys-193, Try-189 and Pro-194 are important determinants of alpha bungarotoxin binding. Tyr-189 may interact directly with cationic groups or participate in aromatic-aromatic interactions while Pro-194 may be necessary to maintain a conformation conductive to neurotoxin binding. PMID- 1736995 TI - Noncovalent interactions of poly(adenosine diphosphate ribose) with histones. AB - Covalent linkage of ADP-ribose polymers to proteins is generally considered essential for the posttranslational modification of protein function by poly(ADP ribosyl)ation. Here we demonstrate an alternative way by which ADP-ribose polymers may modify protein function. Using a highly stringent binding assay in combination with DNA sequencing gels, we found that ADP-ribose polymers bind noncovalently to a specific group of chromatin proteins, i.e., histones H1, H2A, H2B, H3, and H4 and protamine. This binding resisted strong acids, chaotropes, detergents, and high salt concentrations but was readily reversible by DNA. When the interactions of variously sized linear and branched polymer molecules with individual histone species were tested, the hierarchies of binding were branched polymers greater than long, linear polymers greater than short, linear polymers and H1 greater than H2A greater than H2B = H3 greater than H4. For histone H1, the target of polymer binding was the carboxy-terminal domain, which is also the domain most effective in inducing higher order structure of chromatin. Thus, noncovalent interactions may be involved in the modification of histone functions in chromatin. PMID- 1736996 TI - Evidence for processivity and two-step binding of the RNA substrate from studies of J1/2 mutants of the Tetrahymena ribozyme. AB - J1/2 of the Tetrahymena ribozyme, a sequence of three A residues, connects the RNA-binding site to the catalytic core. Addition or deletion of bases from J1/2 improves turnover and substrate specificity in the site-specific endonuclease reaction catalyzed by this ribozyme: G2CCCUCUA5 (S) + G in-equilibrium G2CCCUCU (P) + GA5. These paradoxical enhancements are caused by decreased affinity of the ribozyme for S and P [Young, B., Herschlag, D., & Cech, T.R. (1991) Cell 67, 1007]. An additional property of these mutant ribozymes, decreased fidelity of RNA cleavage, is now analyzed. (Fidelity is the ability to cleave at the correct phosphodiester bond within a particular RNA substrate.) Introduction of deoxy residues to give "chimeric" ribo/deoxyribooligonucleotides changes the positions of incorrect cleavage. Previous work indicated that S is bound to the ribozyme by both base pairing and teritary interactions involving 2'-hydroxyl groups of S. The data herein strongly suggest that the P1 duplex, which consists of S base paired with the 5' exon binding site of the ribozyme, can dock into tertiary interactions in different registers; different 2'-hydroxyl groups of S plug into tertiary contacts with the ribozyme in the different registers. It is concluded that the mutations decrease fidelity by increasing the probability of docking out of register relative to docking in the normal register, thereby giving cleavage at different positions along S. These data also show that the contribution of J1/2 to the teritiary interactions is indirect, not direct. Thus, a structural role of the nonconserved J1/2 is indicated: this sequence positions S to optimize tertiary binding interactions and to ensure cleavage at the phosphodiester bond corresponding to the 5' splice site. Substitution of sulfur for the nonbridging pro-RP oxygen atom at the normal cleavage site has no effect on (kcat/Km)S but decreases the fraction of cleavage at the normal site in reactions catalyzed by the -3A mutant ribozyme, which has all three A residues of J1/2 removed. Thus, the ribozyme chooses where to cleave S after rate-limiting binding of S, indicating that docking can change after binding and suggesting that the ribozyme could act processively. Indeed, it is shown that the +2A ribozyme cleaves at one position along an RNA substrate and then, before releasing that RNA product, cleaves it again.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1736997 TI - Recognition of specific DNA sequences by mitomycin C for alkylation. AB - Synthetic oligodeoxyribonucleotides were reacted with mitomycin C (MC) under conditions which restricted MC to monofunctional alkylating activity. The yields of monofunctional alkylation of oligonucleotides with variable sequence were determined by enzymatic digestion of the reaction mixture to unreacted nucleosides and the product of alkylation, a MC-deoxyguanosine adduct (2), followed by quantitative analysis by HPLC. The relative yields of 2 reflected relative monoalkylation reactivities. They were compared in a series of oligonucleotides having the sequence 5'-NGN' in which the 5'-base was varied while the 3'-base was kept constant as T. Under Na2S2O4 activation conditions a striking enhancement of the yield was observed at the 5'-CG sequence: 36%, compared to 2% at 5'-AG and 4.1% at 5'-TG. The 5'-GG sequence also showed enhanced reactivity although to a lesser extent (14.7%). The enhancements were specific to the duplex state of the oligonucleotides. Using NADPH:cytochrome c reductase as the reducing agent gave similar results. MC activated by acidic pH also displayed 5'-CG alkylation specificity. 10-Decarbamoyl-MC activated by Na2S2O4 showed the same 5'-CG specificity as MC. Replacement of deoxyguanosine by deoxyinosine in the opposite strand at a 5'-CG site abolished the enhancement of alkylation. Such replacement at a 5'-GG site had a similar effect. It was found that the base 3' to the guanine had only a relatively modest modulating effect on the enhanced reactivity of the G at the 5'-CG sequence. This 3'-base effect appeared to be independent of the 5'-base of the 5'-NGN' triplet. The order of reactivity is 3'-(C greater than T greater than A).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1736998 TI - Lateral interactions of pig apolipoprotein A-1 with egg yolk phosphatidylcholine and with cholesterol in mixed monolayers at the triolein-saline interface. AB - Interfacial tensions of egg yolk phosphatidylcholine (PC) and cholesterol monolayers adsorbed at the triolein-saline interface were measured in the presence and absence of pig apolipoprotein A-1 (apoA-1) in the saline phase. In the absence of apoA-1, the adsorptions of PC and cholesterol at the interface from the triolein phase are cooperative, showing large lateral attractive interactions between the PC molecules and the cholesterol molecules in the monolayer. In the presence of apoA-1, the PC adsorption is anti-cooperative, indicating strong lateral attractive interactions between the PC and the apoA-1 molecules, i.e., apparently, repulsive lateral interactions between the PC molecules. On the other hand, lateral interactions of very low magnitude are observed between the cholesterol and apoA-1 molecules in the monolayer. Values of the lateral interaction energy are evaluated from the adsorption data by the Defay-Prigogine-Flory theory of monolayers. The large difference in lateral interaction energy with apoA-1 between PC and cholesterol in a mixed monolayer is discussed in connection with current problems in lipoprotein catabolism: reverse cholesterol transport, alterations in affinity of lipid particles to apoA-1, and formation of high-density lipoproteins and abnormal lipoproteins. PMID- 1736999 TI - Heat capacity changes for protein-peptide interactions in the ribonuclease S system. AB - Two fragments of pancreatic ribonuclease A, a truncated version of S-peptide (residues 1-15) and S-protein (residues 21-124), combine to give a catalytically active complex designated ribonuclease S. We have substituted the wild-type residue Met-13 with six other hydrophobic residues ranging in size from alanine to phenylalanine and have determined the thermodynamic parameters associated with binding of these analogues to S-protein by titration calorimetry in the temperature range 5-25 degrees C. The heat capacity change (delta Cp) associated with binding was obtained from a global analysis of the temperature dependences of the free energies and enthalpies of binding. The delta Cp's were not correlated in any simple fashion with the nonpolar surface area (delta Anp) buried upon binding. PMID- 1737000 TI - Binding of protein synthesis initiation factor 4E to oligoribonucleotides: effects of cap accessibility and secondary structure. AB - The binding of rabbit globin mRNA to the 25-kDa cap binding protein eIF-4E from human erythrocytes was found to be 5.3-fold stronger than the binding of the cap analogue m7GpppG to eIF-4E [Gross et al. (1990) Biochemistry 29, 5008-5012]. In order to investigate whether this effect is due to the longer sequence of nucleotides in globin mRNA or to other features such as cap accessibility or secondary structure, oligoribonucleotide analogues of rabbit alpha-globin mRNA were synthesized by T7 RNA polymerase from a synthetic oligodeoxynucleotide template in the presence of m7GpppG; these oligoribonucleotide analogues possess varying degrees of cap accessibility and secondary structure. Equilibrium association constants for the interaction of these oligoribonucleotides and purified human erythrocyte eIF-4E were obtained from direct fluorescence titration experiments. The data indicate that while the presence of the m7G cap is required for efficient recognition by eIF-4E, the cap need not be completely sterically accessible, since other structural features within the mRNA also influence binding. PMID- 1737001 TI - Use of recombinant biotinylated aequorin in microtiter and membrane-based assays: purification of recombinant apoaequorin from Escherichia coli. AB - Aequorin is a calcium-dependent bioluminescent protein isolated from the hydromedusan Aequorea victoria. The gene for aequorin has been cloned and overexpressed in Escherichia coli [Prasher et al. (1985) Biochem. Biophys. Res. Commun. 126, 1259; Prasher et al. (1987) Biochemistry 26, 1326]. Higher levels of expression have recently been obtained by subcloning aequorin cDNA into the pRC23 plasmid vector such that its expression is under control of the lambda PL promoter [Cormier et al. (1989) Photochem. Photobiol. 49, 509]. Purification of recombinant apoaequorin from E. coli containing this new recombinant plasmid (pAEQ1.3) was accomplished by a two-step procedure involving gel filtration and anion-exchange chromatography on Sephadex G-100 and DEAE-Sepharose, respectively. Typically, 400-500 mg of recombinant protein was obtained from 100 L of fermentation culture. The purified recombinant apoaequorin could be converted to aequorin in high yield upon incubation with synthetic coelenterate luciferin, dissolved oxygen, and a thiol reagent with a photon yield similar to the native photoprotein. Detection of recombinant aequorin in the Dynatech ML1000 Microplate luminometer was linear between 10(-18) and 10(-12) mol, and little loss of specific activity was observed when the protein was derivatized with biotin. The biotinylated derivative was stable when frozen, lyophilized, or stored at 4 degrees C. The feasibility of using biotinylated aequorin as a nonradioactive tag was established by its application in a variety of solid-phase assay formats using the high-affinity streptavidin/biotin interaction. A microtiter-based bioluminescent immunoassay (BLIA) using biotinylated aequorin and the ML1000 luminometer was developed for the detection of subnanogram amounts of a glycosphingolipid (Forsmann antigen). In addition, nanogram to subnanogram quantities of protein antigens and DNA, immobilized on Western and Southern blots, respectively, were detected on instant and X-ray films using biotinylated aequorin. PMID- 1737002 TI - Characterization of the secondary structure of calmodulin in complex with a calmodulin-binding domain peptide. AB - The interaction between calcium-saturated chicken calmodulin and a peptide corresponding to the calmodulin-binding domain of the chicken smooth muscle myosin light chain kinase has been studied by multinuclear and multidimensional nuclear magnetic resonance methods. Extensive 1H and 15N resonance assignments of calmodulin in the complex have been obtained from the analysis of two- and three dimensional nuclear magnetic resonance spectra. The assignment of calmodulin in the complex was facilitated by the use of selective labeling of the protein with alpha-15N-labeled valine, alanine, lysine, leucine, and glycine. These provided reference points during the main-chain-directed analysis of three-dimensional spectra of complexes prepared with uniformly 15N-labeled calmodulin. The pattern of nuclear Overhauser effects (NOE) seen among main-chain amide NH, C alpha H, and C beta H hydrogens indicates that the secondary structure of the globular domains of calmodulin in the complex closely corresponds to that observed in the calcium-saturated state of the protein in the absence of bound peptide. However, the backbone conformation of residues 76-84 adopts an extended chain conformation upon binding of the peptide in contrast to its helical conformation in the absence of peptide. A sufficient number of NOEs between the globular domains of calmodulin and the bound peptide have been found to indicate that the N- and C terminal regions of the peptide interact with the C- and N-terminal domains of calmodulin, respectively. The significance of these results are discussed in terms of recently proposed models for the structure of calmodulin-peptide complexes. PMID- 1737003 TI - Localization of the binding site for streptococcal protein G on human serum albumin. Identification of a 5.5-kilodalton protein G binding albumin fragment. AB - Protein G is a streptococcal cell wall protein with separate and repetitively arranged binding domains for immunoglobulin G (IgG) and human serum albumin (HSA). In this work, the binding of protein G to HSA was studied. The results suggest that a single binding site is present on HSA: the apparent size of the HSA-protein G complex (230 kDa) corresponded to two or three HSA molecules bound to one protein G molecule, and Ouchterlony immunodiffusion did not yield any precipitate between protein G and HSA. HSA was cleaved by pepsin and CNBr into several fragments which were identified by SDS-PAGE and N-terminal amino acid sequencing, and the binding of protein G to the fragments was studied in Western blot experiments. The results indicated that the binding area was located in disulfide loops 6-8, involving both the second (loop 6) and the third (loops 7 and 8) domain of HSA. One of the protein G binding pepsin fragments, with an apparent molecular mass of 5.5 kDa, located in loops 7 and 8, was isolated and found to completely inhibit the binding between protein G and the intact HSA, again suggesting a single protein G binding site on serum albumin. Reducing the disulfide bonds of HSA, and subsequent alkylation of the half-cystine residues, significantly decreased the affinity for protein G. Protein G bound to albumin from baboon, cat, guinea pig, hamster, hen, horse, man, mouse, and rat, but not to albumin from cow, dog, goat, pig, rabbit, sheep, snake, or turkey. PMID- 1737004 TI - Immunogenic peptides corresponding to the dominant antigenic region alanine-597 to cysteine-619 in the transmembrane protein of simian immunodeficiency virus have a propensity to fold in aqueous solution. AB - Two synthetic peptides corresponding to the N- and C-terminal halves of a 23 amino acid sequence representing an immunodominant domain of the simian immunodeficiency virus of macaque origin (SIVmac) were examined for conformational preferences in aqueous solution by proton nuclear magnetic resonance methods. The two constituent peptides, termed A12-7 (Ala597-Ile-Glu-Lys Tyr-Leu-Glu-Asp-Gln-Ala-Gln607) and A12-9 (Leu608-Asn-Ala-Trp-Gly-Cys-Ala-Phe-Arg Gln-Val-Ser619), were found to contain a considerable conformational preference for states in which the backbone phi and psi angles populate the alpha region of the Ramachandran plot. Further, for peptide A12-9, the types and intensities of the nuclear Overhauser effect (NOE) connectivities between protons in the polypeptide backbone suggest that these states appear to include helical turns. The temperature dependence of the amide proton chemical shifts indicates that some degree of intramolecular hydrogen bonding occurs in these peptides. These results are consistent with a model in which immunogenic peptides which induce antibodies reactive with the intact protein from which the peptide sequence was derived contain conformational preferences in water solution for states other than the extended-chain forms typically found in "random coil" peptides. PMID- 1737005 TI - Folding kinetics of T4 lysozyme and nine mutants at 12 degrees C. AB - The kinetics of unfolding and refolding of T4 lysozyme and nine of its mutants have been investigated as a function of guanidinium chloride concentration at 12 degrees C. All show simple two-state, first-order kinetics. Two types of mutants were studied: proline-alanine interchanges and substitutions at position 3 with side chains of varying hydrophobicity. Crystal structures are available for seven of the ten proteins. The effect of mutations on the folding kinetics is more pronounced and complex than on equilibrium thermodynamics. The proteins fall into two broad kinetic classes with one class rather close to the wild type. P86A is a mutant with marked changes in kinetics but only a very small change in stability. Since the 86 position is in the middle of an alpha-helix, the indications are that the helix containing an A residue is more stable in the transition state than one containing a P residue. The other mutants are more complicated, with the refolding and unfolding rates unequally affected by the mutations. On the basis of comparisons with other investigations, we conclude that the rate-determining step in the presence of guanidinium chloride is not the same as in aqueous solution and that it most likely precedes it. The indications are that we are studying the formation of a transition intermediate which is destabilized by the denaturant and which resembles the A intermediate of the framework or molten globule models for protein folding. PMID- 1737006 TI - Stabilities of disulfide bond intermediates in the folding of apamin. AB - Apamin is an 18-residue bee venom peptide with the sequence CNCKAPETALCARRCQQH amide and contains 2 disulfide bonds connecting C-1 to C-11 and C-3 to C-15. In the folding of reduced, unfolded apamin to native apamin with two disulfide bonds, the one-disulfide folding intermediate states are not populated to significant levels. To study the properties of the one-disulfide intermediates, we have synthesized two peptide models to mimic the one-disulfide intermediates, Apa-1 and Apa-2, in which two cysteines in the sequence have been replaced by alanines. These peptides can form only one of the native disulfide bonds, C-1 to C-11 in the case of Apa-1 and C-3 to C-15 in the case of Apa-2. The stabilities of these disulfide bonds have been measured as a function of pH, concentration of urea, and temperature, in order to understand which contributions stabilize the disulfide-bonded structures. Using oxidized and reduced glutathione, the equilibrium constants for forming the disulfide bonds at 25 degrees C and pH 7.0 are 0.018 M for Apa-1 and 0.033 M for Apa-2 and show little dependence on pH or temperature. Both disulfide bonds are destabilized slightly (by approximately a factor of 2) between 0 and 8 M urea. Circular dichroism spectra indicate that although both Apa-1 and Apa-2 exhibit some structure, Apa-2 exhibits more than Apa-1. The results suggest that in the folding of apamin, the one-disulfide intermediate containing the C-3 to C-15 disulfide bond, as in Apa-2, is favored slightly. Secondary structure provides modest stabilization to this intermediate. PMID- 1737007 TI - pH-induced folding/unfolding of staphylococcal nuclease: determination of kinetic parameters by the sequential-jump method. AB - On the basis of previous stopped-flow pH-jump experiments, we have proposed that the acid- and alkaline-induced folding/unfolding transition of staphylococcal nuclease, in the time range 2 ms to 300 s, follows the pathway N0 in equilibrium with D1 in equilibrium with D2 in equilibrium with D3, in which D1, D2, and D3 are three substates of the unfolded state and N0 is the native state. The stopped flow "double-jump" technique has been employed to test this mechanism and to determine the rate constants which would not be accessible by the direct pH jump because of the lack of fluorescence signal, i.e., the rates for the conversion of D1 to D2 and of D2 to D3. In the forward jump, a protein solution kept at pH 7.0 was mixed with an acidic or alkaline solution to the final pH of 3.0 or 12.2, respectively. The mixed solution was kept for varying periods of time, called the delay time, tD. A second mixing (the back jump) was launched to bring the protein solution back to pH 7.0. The time course of the Trp-140 fluorescence signals recovered in the back jump was analyzed as a function of tD. Kinetics of the unfolding were found to be triphasic by the double-jump method, contrary to the monophasic kinetics observed by the direct pH jump. Complex kinetics of unfolding are expected with the proposed kinetic scheme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737008 TI - Engineering surface charge. 1. A method for detecting subunit exchange in Escherichia coli glutathione reductase. AB - The gene gor encoding Escherichia coli glutathione reductase was mutated to create a positively charged N-terminal extension consisting of five arginine residues followed by a factor Xa cleavage site to the enzyme polypeptide chain. The modified protein assembled in vivo to yield a dimeric enzyme with kinetic parameters indistinguishable from those of wild-type glutathione reductase. The N terminal extension could not be released by treatment with factor Xa but could be removed by exposure to trypsin, again without effect on the enzyme activity. The modified enzyme was readily separated from the wild-type enzyme by means of ion exchange chromatography or nondenaturing polyacrylamide gel electrophoresis. Incubation of the modified and wild-type enzymes, separately or as a mixture, with NADH led to their partial inactivation, and activity was restored by exposure to 1 mM reduced glutathione. No hybrid dimer was formed in the mixture of modified and wild-type enzymes, as judged by polyacrylamide gel electrophoresis, strongly suggesting that the inactivation induced by NADH was not due to dissociation of the parental dimers. The addition of otherwise benign positively or negatively charged extensions to the N- or C-terminal regions of the constituent polypeptide chains of oligomeric enzymes offers a simple route to detecting hybrid formation and the causative subunit dissociation and exchange. PMID- 1737009 TI - Engineering surface charge. 2. A method for purifying heterodimers of Escherichia coli glutathione reductase. AB - Two gor genes encoding different mutants of Escherichia coli glutathione reductase have been expressed in the same E. coli cell, leading to the creation of a hybrid form of the enzyme dimer. One of the gor genes carried, in addition to various directed mutations, a 5' extension that encodes a benign penta arginine "arm" added to the N-terminus of the glutathione reductase polypeptide chain [Deonarain, M.P., Scrutton, N.S., & Perham, R.N. (1992) Biochemistry (preceding paper in this issue)]. This made possible, by means of ion-exchange chromatography or nondenaturing polyacrylamide gel electrophoresis, the facile separation of the hybrid enzyme from the two parental forms. Moreover, the two subunits in the hybrid enzyme could be made to carry different mutations. In this way, glutathione reductases with only one active site per dimer were generated: the effects of replacing tyrosine-177 with glycine in the NADPH-binding site, which greatly diminishes the Km for glutathione and switches the kinetic mechanism from ping-pong to ordered sequential, and of replacing His-439 with glutamine in the glutathione-binding site, which greatly diminishes the Km for NADPH, were both found to be restricted to the one active site carrying the mutations. This system of generating separable enzyme hybrids is generally applicable and should make it possible now to undertake a more systematic study of catalytic mechanism and assembly for the many enzymes with quaternary structure. PMID- 1737010 TI - Catalysis at the interface: the anatomy of a conformational change in a triglyceride lipase. AB - The crystal structure of an extracellular triglyceride lipase (from a fungus Rhizomucor miehei) inhibited irreversibly by diethyl p-nitrophenyl phosphate (E600) was solved by X-ray crystallographic methods and refined to a resolution of 2.65 A. The crystals are isomorphous with those of n-hexylphosphonate ethyl ester/lipase complex [Brzozowski, A. M., Derewenda, U., Derewenda, Z. S., Dodson, G. G., Lawson, D. M., Turkenburg, J. P., Bjorkling, F., Huge-Jensen, B., Patkar, S. A., & Thim, L. (1991) Nature 351, 491-494], where the conformational change was originally observed. The higher resolution of the present study allowed for a detailed analysis of the stereochemistry of the change observed in the inhibited enzyme. The movement of a 15 amino acid long "lid" (residues 82-96) is a hinge type rigid-body motion which transports some of the atoms of a short alpha-helix (residues 85-91) by over 12 A. There are two hinge regions (residues 83-84 and 91 95) within which pronounced transitions of secondary structure between alpha and beta conformations are caused by dramatic changes of specific conformational dihedral angles (phi and psi). As a result of this change a hydrophobic area of ca. 800 A2 (8% of the total molecule surface) becomes exposed. Other triglyceride lipases are also known to have "lids" similar to the one observed in the R. miehei enzyme, and it is possible that the general stereochemistry of lipase activation at the oil-water interfaces inferred from the present X-ray study is likely to apply to the entire family of lipases. PMID- 1737011 TI - Crystal structure at 1.5-A resolution of d(CGCICICG), an octanucleotide containing inosine, and its comparison with d(CGCG) and d(CGCGCG) structures. AB - The octadeoxyribonucleotide d(CGCICICG) has been crystallized in space group P(6)5(22) with unit cell dimensions of a = b = 31.0 A and c = 43.7 A, and X-ray diffraction data have been collected to 1.5-A resolution. Precession photographs and the self-Patterson function indicate that 12 base pairs of Z-conformation DNA stack along the c-axis, and the double helices pack in a hexagonal array similar to that seen in other crystals of Z-DNA. The structure has been solved by both Patterson deconvolution and molecular replacement methods and refined in space group P(6)5 to an R factor of 0.225 using 2503 unique reflections greater than 3.0 sigma (F). Comparison of the molecules within the hexagonal lattice with highly refined crystal structures of other Z-DNA reveals only minor conformational differences, most notably in the pucker of the deoxyribose of the purine residues. The DNA has multiple occupancy of C:I and C:G base pairs, and C:I base pairs adopt a conformation similar to that of C:G base pairs. PMID- 1737012 TI - Hexagonal phase forming propensity detected in phospholipid bilayers with fluorescent probes. AB - The fluorescence emission spectrum of N epsilon-dansyl-L-Lys undergoes a marked blue shift when incorporated from aqueous solution into phospholipid bilayers. This shift is greater for membranes composed of dipalmitoleoylphosphatidylcholine than for membranes of dipalmitoleoylphosphatidylethanolamine. With the latter but not the former lipid, the fluorescence emission from N epsilon-dansyl-L-Lys is markedly temperature-dependent. The marked temperature dependence of N epsilon dansyl-L-Lys fluorescence in bilayers of dipalmitoleoylphosphatidylethanolamine is greatest as the sample is heated close to the bilayer to hexagonal phase transition temperature. The fluorescence emission properties of another probe of membrane surface hydrophobicity, Laurdan, also exhibit marked changes at temperatures just below the bilayer to hexagonal phase transition temperature. At these temperatures, the generalized polarization begins to increase rather than decrease with temperature, and the emission intensity decreases markedly. Such effects are not observed over the same temperature range with phosphatidylcholine. Thus, both dansyl-L-lysine and Laurdan provide probes to measure changes in the physical properties of membrane bilayers which occur when these bilayers are heated close to the temperature required for transition to the hexagonal phase. PMID- 1737013 TI - Modulation of progesterone receptor binding to progesterone response elements by positioned nucleosomes. AB - In cells, steroid hormone receptors interact with target enhancer elements on nucleosomes to regulate transcription of genes. To elucidate how nucleosomes can potentially regulate the interactions of steroid receptors with steroid response elements, we have examined the effects of nucleosome positioning and histone source on the binding of the progesterone receptor to DNA elements on nucleosomes reconstituted in vitro. We find that the affinity of the receptor for its response element is dependent on the position of the element within the nucleosome, but not on the histone source, active or inactive chromatin. Our results suggest that the strength of DNA-histone interactions within the nucleosome modulates the binding of progesterone receptor to response elements. Thus, nucleosome positioning is likely to influence the function of steroid receptors in vivo. PMID- 1737014 TI - Miniantibodies: use of amphipathic helices to produce functional, flexibly linked dimeric FV fragments with high avidity in Escherichia coli. AB - We have designed dimeric antibody fragments that assemble in Escherichia coli. They are based on single-chain FV fragments, with a flexible hinge region from mouse IgG3 and an amphiphilic helix fused to the C-terminus of the antibody fragment. The sequence of the helix was taken either from that of a previously reported four-helix bundle design or from a leucine zipper, optionally extended with a short cysteine-containing peptide. The bivalent fragments associate in vivo, either with covalent linkage or with a monomer-dimer equilibrium, and results from ultracentrifugation sedimentation studies and SDS-PAGE are consistent with dimers. All constructs are able to bind to surface-bound antigen under conditions in which only bivalent but not monovalent antibody fragments bind. The covalent bundle helix construct shows binding characteristics nearly identical to those of the much larger whole mouse antibody, resulting in substantially more stable immunoglobulin-antigen complexes than in the case of monovalent fragments. This modular design of natural and engineered protein domains directly leads to a boost of avidity, and it allows the construction of bispecific antibody fragments in functional form in E. coli. PMID- 1737015 TI - Correlation of tryptophan fluorescence intensity decay parameters with 1H NMR determined rotamer conformations: [tryptophan2]oxytocin. AB - While the fluorescence decay kinetics of tyrosine model compounds [Laws, W. R., Ross, J. B. A., Wyssbrod, H. R., Beechem, J. M., Brand, L., & Sutherland, J. C. (1986) Biochemistry 25, 599-607] and the tyrosine residue in oxytocin [Ross, J. B. A., Laws, W. R., Buku, A., Sutherland, J. C., & Wyssbrod, H. R. (1986) Biochemistry 25, 607-612] can be explained in terms of heterogeneity derived from the three ground-state chi 1 rotamers, a similar correlation has yet to be directly observed for a tryptophan residue. In addition, the asymmetric indole ring might also lead to heterogeneity from chi 2 rotations. In this paper, the time-resolved and steady-state fluorescence properties of [tryptophan2]oxytocin at pH 3 are presented and compared with 1H NMR results. According to the unrestricted analyses of individual fluorescence decay curves taken as a function of emission wavelength and a global analysis of these decay curves for common emission wavelength-independent decay constants, only three exponential terms are required. In addition, the preexponential weighting factors (amplitudes) have the same relative relationship (weights) as the 1H NMR-determined chi 1 rotamer populations of the indole side chain. 15N was used in heteronuclear coupling experiments to confirm the rotamer assignments. Inclusion of a linked function restricting the decay amplitudes to the chi 1 rotamer populations in the individual decay curve analyses and in the global analysis confirms this correlation. According to qualitative nuclear Overhauser data, there are two chi 2 populations. Depending upon the degree of correlation between chi 2 and chi 1, there may be from three to six side-chain conformations for the tryptophan residue. The combined fluorescence and NMR results are consistent with a rotamer model in which either (i) the chi 2 rotations are fast compared to the fluorescence intensity decay of the tryptophan residue, (ii) environmental factors affecting fluorescence intensity decay properties are dominated by chi 1 interactions, or (iii) the chi 2 and chi 1 rotations are highly correlated. PMID- 1737016 TI - Conformational changes in the metal-binding sites of cardiac troponin C induced by calcium binding. AB - Isotope labeling of recombinant normal cardiac troponin C (cTnC3) with 15N enriched amino acids and multidimensional NMR were used to assign the downfield shifted amide protons of Gly residues at position 6 in Ca(2+)-binding loops II, III, and IV, as well as tightly hydrogen-bonded amides within the short antiparallel beta-sheets between pairs of Ca(2+)-binding loops. The amide protons of Gly70, Gly110, and Gly146 were found to be shifted significantly downfield from the remaining amide proton resonances in Ca(2+)-saturated cTnC3. No downfield-shifted Gly resonance was observed from the naturally inactive site I. Comparison of downfield-shifted amide protons in the Ca(2+)-saturated forms of cTnC3 and CBM-IIA, a mutant having Asp65 replaced by Ala, demonstrated that Gly70 is hydrogen bonded to the carboxylate side chain of Asp65. Thus, the hydrogen bond between Gly and Asp in positions 6 and 1, respectively, of the Ca(2+) binding loop appears crucial for maintaining the integrity of the helix-loop helix Ca(2+)-binding sites. In the apo- form of cTnC3, only Gly70 was found to be shifted significantly downfield with respect to the remaining amide proton resonances. Thus, even in the absence of Ca2+ at binding site II, the amide proton of Gly70 is strongly hydrogen bonded to the side-chain carboxylate of Asp65. The amide protons of Ile112 and Ile148 in the C-terminal domain and Ile36 in the N-terminal domain data-sheets exhibit chemical shifts consistent with hydrogen-bond formation between the pair of Ca(2+)-binding loops in each domain of Ca(2+)-saturated cTnC3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737017 TI - Triple-helix formation and cooperative binding by oligodeoxynucleotides with a 3' 3' internucleotide junction. AB - Triple-helix formation by oligodeoxynucleotides in a sequence-specific manner is limited to polypurine tracts of duplex DNA. To increase the number of biologically relevant targets for triple-helix formation, we have utilized oligodeoxynucleotides containing a 3'-3' internucleotide junction to allow for binding to opposite strands of duplex DNA. Molecular modeling was used to aid in the design of the xylose dinucleoside linker 1 that is rigid and minimizes the number of conformers to minimize the entropy of binding. Thermal denaturation studies show that a 3'-3'-linked oligodeoxynucleotide, bearing nine nucleotides on each side of the linker, has a higher Tm (47.6 degrees C) than that of a 21 mer binding to a single polypurine tract (45.3 degrees C). Binding domain minimization studies and sequence-specific alkylation of a target duplex demonstrate a high degree of cooperativity between the two triple-helix binding domains, thus allowing for an increase in the number of biologically relevant targets for triple-helix formation. PMID- 1737018 TI - A fully active variant of dihydrofolate reductase with a circularly permuted sequence. AB - The amino acid sequence of mouse dihydrofolate reductase was permuted circularly at the level of the gene. By transposing the 3'-terminal half of the coding sequence to its 5' terminus, the naturally adjacent amino and carboxyl termini of the native protein were fused, and one of the flexible peptide loops at the protein surface was cleaved. The steady-state kinetic constants, the dissociation constants of folate analogues, and the degree of activation by both mercurials and salt as well as the resistance toward digestion by trypsin were almost indistinguishable from those of a recombinant wild-type protein. Judged by these criteria, the circularly permuted variant has the same active site and overall structure as the wild-type enzyme. The only significant difference was the lower stability toward guanidinium chloride and the lower solubility of the circularly permuted variant. This behavior may be due to moving a mononucleotide binding fold from the interior of the sequence to the carboxyl terminus. Thus, dihydrofolate reductase requires neither the natural termini nor the cleaved loop for stability, for the conformational changes that accompany catalysis as well as the binding of inhibitors, and for the folding process. PMID- 1737019 TI - Diadenosine tetraphosphate binding protein from human HeLa cells: purification and characterization. AB - The ubiquitous dinucleotide P1,P4-di(adenosine-5') tetraphosphate (Ap4A) has been proposed to be involved in DNA replication and cell proliferation, DNA repair, platelet aggregation, and vascular tonus. A protein binding specifically to Ap4A is associated with a multiprotein form of DNA polymerase alpha (pol alpha 2) in HeLa cells. The Ap4A binding protein from HeLa cells has been purified to homogeneity starting from pol alpha 2 complex. The Ap4A binding protein is hydrophobic and is resolved from the pol alpha 2 complex by hydrophobic interaction chromatography on butyl-Sepharose and subsequently purified to homogeneity by chromatography on Mono-Q and Superose-12 FPLC columns. The Ap4A binding activity elutes as a single symmetrical peak upon gel filtration with a molecular mass of 200 kDa. Upon polyacrylamide gel electrophoresis under nondenaturing conditions, the purified protein migrates as a single protein of 200 kDa. Upon electrophoresis under denaturing conditions, the binding activity is resolved into two polypeptides of 45 and 22 kDa, designated as A1 and A2, respectively. A1 and A2 can be cross-linked using the homobifunctional cross linking agent disuccinimidyl suberate. The cross-linked protein migrates as a single protein of 210 kDa on polyacrylamide gels under denaturing conditions, suggesting that these two polypeptides are subunits of a single protein. The purified protein binds Ap4A efficiently, and by Scatchard analysis, we have determined a dissociation constant of 0.25 microM, indicating high affinity of Ap4A binding protein to its ligand. ATP is not required for the binding activity. The nonionic detergent Triton X-100 is necessary for stabilizing the purified protein. Amino acid composition analysis indicates that A1 and A2 are distinct. PMID- 1737020 TI - Differential scanning calorimetric study of the thermal unfolding of mutant forms of phage T4 lysozyme. AB - In two recent papers, we reported the effects of several point mutations on the thermodynamics of the thermal unfolding of the lysozyme of phage T4 as determined by differential scanning calorimetry. The mutants studied were R96H [Kitamura, S., & Sturtevant, J.M. (1989) Biochemistry 28, 3788-3792] and T157 replaced by A, E, I, L, N, R, and V [Connelly, P., Ghosaini, L., Hu, C.-Q., Kitamura, S., Tanaka, A., & Sturtevant, J.M. (1991) Biochemistry 30, 1887-1891]. Here we report the results of a similar study of the single mutations A82P, A93P, and G113A and the double mutation C54T:C97A. The three single mutants all show small apparent stabilization at pH 2.5 and 46.2 degrees C (the denaturational temperature of the wild-type protein), amounting to -0.5 +/- 0.4 kcal mol-1 in free energy, whereas the double mutant shows a weak apparent destabilization, +0.8 +/- 0.4 kcal mol-1. As in all our previous studies of mutant proteins, the enthalpy changes produced by these mutations are in general of much larger magnitude than the corresponding free energy changes and frequently of opposite sign. PMID- 1737021 TI - The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. AB - Previous studies by Wishart et al. [Wishart, D. S., Sykes, B. D., & Richards, F. M. (1991) J. Mol. Biol. (in press)] have demonstrated that 1H NMR chemical shifts are strongly dependent on the character and nature of protein secondary structure. In particular, it has been found that the 1H NMR chemical shift of the alpha-CH proton of all 20 naturally occurring amino acids experiences an upfield shift (with respect to the random coil value) when in a helical configuration and a comparable downfield shift when in a beta-strand extended configuration. On the basis of these observations, a technique is described for rapidly and quantitatively determining the identity, extent, and location of secondary structural elements in proteins based on the simple inspection of the alpha-CH 1H resonance assignments. A number of examples are provided to demonstrate both the simplicity and the accuracy of the technique. This new method is found to be almost as accurate as the more traditional NOE-based methods of determining secondary structure and could prove to be particularly useful in light of the recent development of sequential assignment techniques which are now almost NOE independent [Ikura, M., Kay, L. E., & Bax, A. (1990) Biochemistry 29, 4659-4667]. We suggest that this new procedure should not necessarily be seen as a substitute to existing rigorous methods for secondary structure determination but, rather, should be viewed as a complement to these approaches. PMID- 1737022 TI - Proton nuclear Overhauser effect study of the heme active site structure of chloroperoxidase. AB - Chloroperoxidase, a glycoprotein from the mold Caldariomyces fumago, has been investigated in its ferric low-spin cyanide-ligated form through use of nuclear Overhauser effect (NOE) spectroscopy to provide information on the heme pocket electronic/molecular structure. Spin-lattice relaxation times for the hyperfine shifted heme resonances were found to be three times less than those in horseradish peroxidase. This must reflect a slower electronic relaxation rate for chloroperoxidase than for horseradish peroxidase as a consequence of axial ligation of cysteine in the former versus histidine in the latter enzyme. Isoenzymes A1 and A2 of chloroperoxidase show the largest chemical shift differences near the heme propionate on the basis of NOE measurements. This suggests that the primary structure differences for the two isoenzymes are communicated to the heme group through the ring propionate substituents. A downfield peak has been detected in chloroperoxidase with chemical shift, T1, and line width characteristics similar to those of the C epsilon-H proton of the distal histidine residue. The NOE pattern and T1's of the peaks in the 0.0 to 5.0 ppm upfield region are consistent with the presence of an arginine amino acid residue in the heme pocket near either the 1-CH3 or 3-CH3 group. Existence of catalytically important distal histidine and arginine amino acid residues in chloroperoxidase shows it to be structurally similar to peroxidases rather than to the often compared monooxygenase, cytochrome P-450. This result supports the earlier conclusions of Sono et al. [Sono, M., Dawson, J.H., Hall, K., & Hager, L.P. (1986) Biochemistry 25, 347-356]. PMID- 1737023 TI - Mutational analysis of carbamyl phosphate synthetase. Substitution of Glu841 leads to loss of functional coupling between the two catalytic domains of the synthetase subunit. AB - The synthetase subunit of Escherichia coli carbamyl phosphate synthetase has two catalytic nucleotide-binding domains, one involved in the activation of HCO3- and the second in phosphorylation of carbamate. Here we show that a Glu841----Lys841 substitution in a putative ATP-binding domain located in the carboxyl half of the synthetase abolishes overall synthesis of carbamyl phosphate with either glutamine or NH3 as the nitrogen source. Measurements of partial activities indicate that while HCO3(-)-dependent ATP hydrolysis at saturating concentrations of substrate proceeds at higher than normal rates, ATP synthesis from ADP and carbamyl phosphate is nearly completely suppressed by the mutation. These results indicate Glu841 to be an essential residue for the phosphorylation of carbamate in the terminal step of the catalytic mechanism. The Lys841 substitution also affects the kinetic properties of the HCO3- activation site. Both kcat and Km for ATP increase 10-fold, while Km for HCO3- is increased 100-fold. Significantly, NH3 decreases rather than stimulates Pi release from ATP in the HCO3(-)-dependent ATPase reaction. The increase in kcat of the HCO3(-)-dependent ATPase reaction, and an impaired ability of the Lys841 enzyme to catalyze the reaction of NH3 with carboxy phosphate, strongly argues for interactions between the two catalytic ATP sites that couple the formation of enzyme-bound carbamate with its phosphorylation. PMID- 1737024 TI - A low molecular weight platelet inhibitor of factor XIa: purification, characterization, and possible role in blood coagulation. AB - A low molecular weight platelet inhibitor of factor XIa (PIXI) has been purified 250-fold from releasates of washed and stimulated human platelets. Molecular weight estimates of 8400 and 8500 were determined by gel filtration and SDS polyacrylamide gel electrophoresis, respectively, although a second band of Mr 5000 was present upon electrophoresis. The inhibitor does not appear to be one of the platelet-specific, heparin-binding proteins, since it neither bound to nor was affected by heparin. An amount of PIXI which inhibited by 50% factor XIa cleavage of the chromogenic substrate S2366 (Pyr-Glu-Pro-Arg-pNA-2H2O) only slightly inhibited (5-9%) factor XIIa, plasma kallikrein, plasmin, and activated protein C and did not inhibit factor Xa, thrombin, tPA, or trypsin, suggesting specificity for factor XIa. Kinetic analyses of the effect of PIXI on factor XIa activity demonstrated mixed-type, noncompetitive inhibition of S2366 cleavage and of factor IX activation with Ki's of 7 x 10(-8) and 3.8 x 10(-9) M, respectively. Immunoblot analysis showed that PIXI is not the inhibitory domain of protease nexin II, a potent inhibitor of factor XIa also secreted from platelets. Amino acid analysis showed that PIXI has no cysteine residues and, therefore, is not a Kunitz-type inhibitor. PIXI can prevent stable complex formation between alpha 1 protease inhibitor and factor XIa light chain as demonstrated by SDS polyacrylamide gel electrophoresis. The inhibition by PIXI of factor XIa catalyzed activation of factor IX and its capacity to prevent factor XIa inactivation by alpha 1-protease inhibitor, combined with the specificity of PIXI for factor XIa among serine proteases found in blood, suggest a role for PIXI in the regulation of intrinsic coagulation. PMID- 1737025 TI - Covalent modification and active site-directed inactivation of a low molecular weight phosphotyrosyl protein phosphatase. AB - Covalent modification experiments were conducted in order to identify active site residues of the 18-kDa cytoplasmic phosphotyrosyl protein phosphatases. The enzyme was inactivated by diethyl pyrocarbonate, phenylglyoxal, cyclohexanedione, iodoacetate, iodoacetamide, phenylarsine oxide, and certain epoxides in a manner consistent with the modification of active site residues. Phenylglyoxal and cyclohexanedione both bind to the active site in a rapid preequilibrium process and thus act as active site-directed inhibitors. The pH dependencies of the inactivation by iodoacetate and by iodoacetamide were examined in detail and compared with rate data for the alkylation of glutathione as a model compound. The enzyme inactivation data permitted the determination of pKa values of two reactive cysteines at or near the active site. Although phosphomycin is simply a competitive inhibitor of the enzyme, it was found that 1,2-epoxy-3-(p nitrophenoxy)propane (EPNP) and (R)- and (S)-benzylglycidol act as irreversible covalent inactivators, consistent with the importance of a hydrophobic moiety on the substrate in controlling substrate specificity. EPNP exhibits characteristics of an active site-directed inactivator, with a preequilibrium binding constant somewhat smaller than that of phosphate ion. The pH dependencies of inactivation of EPNP and (S)-benzylglycidol are identical to that observed for iodoacetamide and similar to that for iodoacetate, suggesting that they modify similar groups. Sequencing of the tryptic digests of the EPNP-labeled enzyme indicates that Cys 62 and Cys-145 are labeled. Phenylarsine oxide acts as a very slow, tight-binding inhibitor of the enzyme. The results are interpreted in terms of an active site model that incorporates a histidine-cysteine ion pair, similar to that present in papain. PMID- 1737026 TI - Characterization of a calcium- and lipid-dependent protein kinase associated with the plasma membrane of oat. AB - A protein kinase that is activated by calcium and lipid has been partially purified from the plasma membrane of oat roots. This protein kinase cross-reacts with four monoclonal antibodies directed against a soluble calcium-dependent protein kinase from soybean described previously [Putman-Evans, C. L., Harmon, A. C., & Cormier, M. J. (1990) Biochemistry 29, 2488-2495; Harper, J. F., Sussman, M. R., Schaller, G. E., Putnam-Evans, C., Charbonneau, H., & Harmon, A. C. (1991) Science 252, 951-954], indicating that the oat enzyme is a member of this calcium dependent protein kinase family. Immunoblots demonstrate that the membrane derived protein kinase is slightly larger than that observed in the cytosolic fraction of oat. Limited digestion of the membrane-derived kinase with trypsin generates a smaller water-soluble kinase that is still activated by calcium but is no longer activated by lipid. When posthomogenization proteolysis is minimized, the bulk of the immunoreactive kinase material is localized in the membrane. These results suggest that a calcium-dependent protein kinase observed in the supernatant fraction of oat extracts may originate in situ from a calcium- and lipid-dependent protein kinase which is associated with the oat plasma membrane. They further indicate that, in contrast to animal cells, the predominant calcium- and lipid-dependent protein kinase associated with the plasma membrane of plant cells has biochemical properties and amino acid sequence unlike protein kinase C. PMID- 1737027 TI - Proteins associated with the messenger ribonucleoprotein particle for the estrogen-regulated apolipoprotein II mRNA. AB - The stability of the mRNA for apolipoprotein (apo) II is regulated by estrogen [Gordon et al. (1988) J. Biol. Chem. 263, 2625-2631]. On the hypothesis tha estrogen regulation of apoII mRNA stability is mediated through mRNA-protein interaction, we have examined the messenger ribonucleoprotein particle (mRNP) for apoII mRNA following release from chicken liver polyribosomes. Polyribosomes containing undegraded apoII mRNA were obtained when tissue was homogenized without detergent, and polyribosomes were isolated following simultaneous addition of detergent and magnesium to a 20000g supernatant. ApoII mRNP released by EDTA sedimented at 12-18 S in sucrose gradients, and banded at rho = 1.4 g/mL in CsCl isopycnic centrifugation, indicative of a 3:1 ratio of protein to mRNA. A fraction in which apoII mRNP was enriched to 40-50% of total mRNP was prepared by successive size fractionation steps on sucrose gradients. Proteins associated with sucrose gradient enriched apoII mRNP were examined by iodination of UV-cross linked proteins followed by SDS-polyacrylamide gel electrophoresis. Comparisons of proteins in highly enriched apoII mRNP to proteins in mRNP from non-estrogen treated rooster liver did not reveal any differences. This result suggests that the major proteins associated with apoII mRNA are mRNP proteins also associated with the bulk of liver mRNAs. PMID- 1737028 TI - Disulfide exchange folding of insulin-like growth factor I. AB - The disulfide exchange folding properties of insulin-like growth factor I (IGF-I) have been analyzed in a redox buffer containing reduced (10 mM) and oxidized (1 mM) glutathione. Under these conditions, the 3 disulfide bridges of the 70 amino acid peptide were not quantitatively formed. Instead, five major forms of IGF-I were detected, and these components were concluded to be in equilibrium as their relative amounts were similar starting from either reduced, native, or a mismatched variant of IGF-I containing two non-native disulfides. The different components in the mixtures were trapped by thiol alkylation using vinylpyridine and subsequently isolated by reverse-phase HPLC. The purified variants were further characterized using plasma desorption mass spectrometry and peptide mapping. Two of the five different forms were identified as native and mismatched IGF-I. One form was a variant with only one disulfide bond, and the other two major components had two disulfides formed. In a separate experiment, early refolding intermediates were trapped by pyridylethylation after only 90 s of refolding in the glutathione buffer, starting from reduced IGF-I. The intermediates were identical to the components observed at equilibrium, but at different relative concentrations. On the basis of the disulfide bond patterns of the different components in the equilibrium mixtures, we conclude that the disulfide between cysteines-47 and -52 in IGF-I is an unfavorable high-energy bond that may exist in the native molecule in a strained configuration. PMID- 1737029 TI - Mutations at the dimer, hexamer, and receptor-binding surfaces of insulin independently affect insulin-insulin and insulin-receptor interactions. AB - Mutagenesis of the dimer- and hexamer-forming surfaces of insulin yields analogues with reduced tendencies to aggregate and dramatically altered pharmacokinetic properties. We recently showed that one such analogue, HisB10--- Asp, ProB28----Lys, LysB29----Pro human insulin (DKP-insulin), has enhanced affinity for the insulin receptor and is useful for studying the structure of the insulin monomer under physiologic solvent conditions [Weiss, M. A., Hua, Q. X., Lynch, C. S., Frank, B. H., & Shoelson, S. E. (1991) Biochemistry 30, 7373-7389]. DKP-insulin retains native secondary and tertiary structure in solution and may therefore provide an appropriate baseline for further studies of related analogues containing additional substitutions within the receptor-binding surface of insulin. To test this, we prepared a family of DKP analogues having potency altering substitutions at the B24 and B25 positions using a streamlined approach to enzymatic semisynthesis which negates the need for amino-group protection. For comparison, similar analogues of native human insulin were prepared by standard semisynthetic methods. The DKP analogues show a reduced tendency to self associate, as indicated by 1H-NMR resonance line widths. In addition, CD spectra indicate that (with one exception) the native insulin fold is retained in each analogue; the exception, PheB24----Gly, induces similar perturbations in both native insulin and DKP-insulin backgrounds. Notably, analogous substitutions exhibit parallel trends in receptor-binding potency over a wide range of affinities: D-PheB24 greater than unsubstituted greater than GlyB24 greater than SerB24 greater than AlaB25 greater than LeuB25 greater than SerB25, whether the substitution was in a native human or DKP-insulin background. Such "template independence" reflects an absence of functional interactions between the B24 and B25 sites and additional substitutions in DKP-insulin and demonstrates that mutations in discrete surfaces of insulin have independent effects on protein structure and function. In particular, the respective receptor-recognition (PheB24, PheB25), hexamer-forming (HisB10), and dimer-forming (ProB28, LysB29) surfaces of insulin may be regarded as independent targets for protein design. DKP-insulin provides an appropriate biophysical model for defining structure function relationships in a monomeric template. PMID- 1737030 TI - Binding of basic peptides to acidic lipids in membranes: effects of inserting alanine(s) between the basic residues. AB - We studied the binding of peptides containing five basic residues to membranes containing acidic lipids. The peptides have five arginine or lysine residues and zero, one, or two alanines between the basic groups. The vesicles were formed from mixtures of a zwitterionic lipid, phosphatidylcholine, and an acidic lipid, either phosphatidylserine or phosphatidylglycerol. Measuring the binding using equilibrium dialysis, ultrafiltration, and electrophoretic mobility techniques, we found that all peptides bind to the membranes with a sigmoidal dependence on the mole fraction of acidic lipid. The sigmoidal dependence (Hill coefficient greater than 1 or apparent cooperativity) is due to both electrostatics and reduction of dimensionality and can be described by a simple model that combines Gouy-Chapman-Stern theory with mass action formalism. The adjustable parameter in this model is the microscopic association constant k between a basic residue and an acidic lipid (1 less than k less than 10 M-1). The addition of alanine residues decreases the affinity of the peptides for the membranes; two alanines inserted between the basic residues reduces k 2-fold. Equivalently, the affinity of the peptide for the membrane decreases 10-fold, probably due to a combination of local electrostatic effects and the increased loss of entropy that may occur when the more massive alanine-containing peptides bind to the membrane. The arginine peptides bind more strongly than the lysine peptides: k for an arginine residue is 2-fold higher than for a lysine residue. Our results imply that a cluster of arginine and lysine residues with interspersed electrically neutral amino acids can bind a significant fraction of a cytoplasmic protein to the plasma membrane if the cluster contains more than five basic residues. PMID- 1737031 TI - Distances between the antigen-binding sites of three murine antibody subclasses measured using neutron and X-ray scattering. AB - For three different murine immunoglobulins (IgG subclasses 1, 2a, and 2b), the distances between their antigen-binding sites have been measured using neutron scattering from deuterated antigens complexed with proteated IgG. Neutron scattering data were measured for each antibody-antigen complex in a 41% D2O solvent. Unlike the proteated antibody molecule, the deuterated antigens are strongly contrasted against the 41% D2O solvent and give rise to a scattering profile that contains an interference term related to the distance between the deuterated antigens. For all three subclasses, the damping of this interference term, which gives information on the relative flexibility of the antigen-binding sites, indicates that a single distance is inadequate to describe the observed scattering and a distribution of distances is needed. The scattering profile has been modeled for each subclass to give the mean distance between the antigens and the variance of this distance. For all three IgG subclasses, the mean distance is between 117 and 134 A, and the variance is large (approximately 40 A), indicating a high degree of flexibility of the Fab arms. Small-angle X-ray scattering measurements on the same samples are consistent with the neutron-scattering results. PMID- 1737032 TI - Role of hydrophobic forces in bilayer adhesion and fusion. AB - With the aim of gaining more insight into the forces and molecular mechanisms associated with bilayer adhesion and fusion, the surface forces apparatus (SFA) was used for measuring the forces and deformations of interacting supported lipid bilayers. Concerning adhesion, we find that the adhesion between two bilayers can be progressively increased by up to two orders of magnitude if they are stressed to expose more hydrophobic groups. Concerning fusion, we find that the most important force leading to direct fusion is the hydrophobic attraction acting between the (exposed) hydrophobic interiors of bilayers; however, the occurrence of fusion is not simply related to the strength of the attractive interbilayer forces but also to the internal bilayer stresses (intrabilayer forces). For all the bilayer systems studied, a single basic fusion mechanism was found in which the bilayers do not "overcome" their short-range repulsive steric-hydration forces. Instead, local bilayer deformations allow these repulsive forces to be "bypassed" via a mechanism that is like a first-order phase transition, with a sudden instability occurring at some critical surface separation. Some very slow relaxation processes were observed for fluid bilayers in adhesive contact, suggestive of constrained lipid diffusion within the contact zone. PMID- 1737033 TI - Polarity decrease at the adhesive junction between two model membranes containing gangliosides. AB - The increased electrical conductance previously observed between two model membranes containing gangliosides suggests the creation of a new environment in the adhesive junction [Brewer, G. J., & Thomas, P.D. (1984) Biochim. Biophys. Acta 776, 279]. In order to provide a mechanism for this novel finding, we now report an investigation of the micropolarity in the adhesive junction. Emission from the fluorescent probe PRODAN is a sensitive measure of polarity of the probe environment. A bimodal linear relationship correlates the emission wavelength from PRODAN with the inverse of solvent dielectric constant (1/epsilon). A better single linear relationship is obtained using Reichardt's relative polarity measure (RPM). Creation of two macroscopic spherical lipid bilayers from phosphatidylcholine, brain gangliosides, and PRODAN allowed selective excitation and observation of fluorescence from either a single bilayer or the double bilayer in the adhesive junction. The reported PRODAN polarity of -0.57 in a single ganglioside-containing membrane was midway between the polarity of water and n-hexane, suggesting PRODAN localization near the lipid carbonyls. The adhesive junctional region exhibited two new less polar environments of PRODAN fluorescence, RPM = -0.45 and -0.29. These measures are consistent with a relatively dehydrated immobilized phase. These changes were not observed in the adhesion zone between two membranes made with phosphatidylcholine without gangliosides. The changes in molecular structure in the junction that could be responsible for the altered PRODAN emission are discussed. A decrease in the hydrocarbon thickness of junctional membranes or a decrease in the aqueous junctional polarity could be responsible for the polarity decrease reported by PRODAN. PMID- 1737034 TI - Congregation of gangliosides at the junction between two model membranes. AB - The diversity and distribution of gangliosides in vertebrate tissue suggests an important role in cellular recognition. Two types of experiments are reported to test the hypothesis that gangliosides can congregate to form an adhesive junction between two membranes. First, to monitor ganglioside distribution and mobility in different regions of two large spherical bilayer membranes, fluorescent derivatives of natural gangliosides were synthesized. Second, the cation carrier nonactin was used as a conductance probe to measure the membrane surface potential, which would be altered if there were a redistribution of the charged gangliosides. These studies were conducted in large spherical artificial membranes made from egg phosphatidylcholine or oleoylpalmitoylphosphatidylcholine with 0-12 mol % bovine brain gangliosides dissolved in n-decane. The fluorescent gangliosides utilized were lucifer yellow adducts to the sialic acids (LY gangliosides) or a cis-paranaric acid substitution of the N-acyl moiety in the ceramide portion of gangliosides GM1 and GD1a (paranaryl-GM1 and paranaryl-GD1a). The polarized fluorescence from the adhesive junction between two membranes containing LY-gangliosides or either paranarylganglioside was compared to that in nonadhesive regions. For LY-gangliosides, total fluorescence in the junction decreased with time, possibly due to electrostatic repulsion of this highly charged derivative. For paranarylgangliosides, fluorescence in the junction increased 7-fold with time, suggesting congregation of this ganglioside. In both cases, a measure of rotational mobility, fluorescence anisotropy, increased dramatically, about 2-fold, as expected for restricted mobility of adhesive compounds. Independent evidence for congregation of charge-bearing gangliosides was found with the conductance probe nonactin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737035 TI - Correlation between phosphorylation of the chemotaxis protein CheY and its activity at the flagellar motor. AB - Phosphorylation of the chemotaxis protein CheY by its kinase CheA appears to play a central role in the process of signal transduction in bacterial chemotaxis. It is presumed that the role is activation of CheY which results in clockwise (CW) flagellar rotation. The aim of this study was to determine whether this activity of CheY indeed depends on the protein being phosphorylated. Since the phosphorylation of CheY can be detected only in vitro, we studied the ability of CheY to cause CW rotation in an in vitro system, consisting of cytoplasm-free envelopes of Salmonella typhimurium or Escherichia coli having functional flagella. Envelopes containing just buffer rotated only counterclockwise. Inclusion of CheY caused 14% of the rotating envelopes to go CW. This fraction of CW-rotating envelopes was not altered when the phosphate potential in the envelopes was lowered by inclusion of ADP together with CheY in them, indicating that CheY has a certain degree of activity even without being phosphorylated. Attempts to increase the activity of CheY in the envelopes by phosphorylation were not successful. However, when CheY was inserted into partially-lysed cells (semienvelopes) under phosphorylating conditions, the number of CW-rotating cells increased 3-fold. This corresponds to more than a 100-fold increase in the activity of a single CheY molecule upon phosphorylation. It is concluded that nonphosphorylated CheY can interact with the flagellar switch and cause CW rotation, but that this activity is increased by at least 2 orders of magnitude by phosphorylation. This increase in activity requires additional cytoplasmic constituents, the identity of which is not yet known. PMID- 1737036 TI - Profilin-actin complexes directly elongate actin filaments at the barbed end. AB - We demonstrate that the profilin-G-actin complex can elongate actin filaments directly at the barbed end but cannot bind to the pointed end. During elongation, the profilin-actin complex binds to the barbed filament end, whereupon profilin is released, leaving the actin molecule behind. This was first proposed by Tilney [Tilney, L. G., et al. (1983) J. Cell Biol. 97, 112-124] and demonstrated by Pollard and Cooper [(1984) Biochemistry 23, 6631-6641] by electron microscopy. We show that a model without any outside energy supply, in contrast to the mechanism proposed by Pollard and Cooper, can be fitted to our and their [Kaiser et al. (1986) J. Cell Biol. 102, 221-226] findings. Input of outside energy is necessary only if profilin-mediated elongation continues after free G-actin has been lowered to or below the critical concentration observed at the barbed end in the absence of profilin. PMID- 1737037 TI - Effects of salt concentration and H1 histone removal on the differential scanning calorimetry of nuclei. AB - The effects of increasing NaCl concentrations on the melting profiles of chromatin in isolated nuclei contradicted published claims that structural transitions near 76 degrees C (Tn-7), near 89 degrees C (Tn-8), and near 105 degrees C (Tn-10) were respectively the melting of linker DNA, the melting of extended nucleosomal strands, and the collapse of nucleosomes in the 300-A fiber. Contrary to expectations of such an interpretation, decreases in salt concentration stabilized Tn-7 and failed to eliminate Tn-10. Moreover, nuclei depleted of H1 histone, which is known to be essential for the formation of the 300-A fiber, gave the same melting profile as intact nuclei with regard to the relative magnitudes of Tn-8 and Tn-10. The effect of salt concentration on the melting profiles and the insensitivity of Tn-8 and Tn-10 to H1 histone removal supports the notion that Tn-7 is the collapse of the nucleosome while Tn-8 and Tn 10 are respectively the unstacking of nucleotide bases in relaxed chromatin and supercoiled chromatin. The identification of Tn-8 as the unstacking of bases in relaxed DNA, and Tn-10 as unstacking in supercoiled DNA, shows that scanning calorimetry can be used to measure the state of repair of DNA in the nucleus. The gain in Tn-8 at the expense of Tn-10 that is seen as the mitotic index drops and differentiation occurs suggests that nicks accumulate in the DNA, perhaps because the gross aggregation of the inactive majority of the chromatin makes it inaccessible to repair enzymes. PMID- 1737038 TI - 31P NMR spectra of oligodeoxyribonucleotide duplex lac operator-repressor headpiece complexes: importance of phosphate ester backbone flexibility in protein-DNA recognition. AB - The 31P NMR spectra of various 14-base-pair lac operators bound to both wild-type and mutant lac repressor headpiece proteins were analyzed to provide information on the backbone conformation in the complexes. The 31P NMR spectrum of a wild type symmetrical operator, d(TGTGAGCGCTCACA)2, bound to the N-terminal 56-residue headpiece fragment of a Y7I mutant repressor was nearly identical to the spectrum of the same operator bound to the wild-type repressor headpiece. In contrast, the 31P NMR spectrum of the mutant operator, d(TATAGAGCGCTCATA)2, wild-type headpiece complex was significantly perturbed relative to the wild-type repressor-operator complex. The 31P chemical shifts of the phosphates of a second mutant operator, d(TGTGTGCGCACACA)2, showed small but specific changes upon complexation with either the wild-type or mutant headpiece. The 31P chemical shifts of the phosphates of a third mutant operator, d(TCTGAGCGCTCAGA)2, showed no perturbations upon addition of the wild-type headpiece. The 31P NMR results provide further evidence for predominant recognition of the 5'-strand of the 5' TGTGA/3'-ACACT binding site in a 2:1 protein to headpiece complex. It is proposed that specific, strong-binding operator-protein complexes retain the inherent phosphate ester conformational flexibility of the operator itself, whereas the phosphate esters are conformationally restricted in the weak-binding operator protein complexes. This retention of backbone torsional freedom in strong complexes is entropically favorable and provides a new (and speculative) mechanism for protein discrimination of different operator binding sites. It demonstrates the potential importance of phosphate geometry and flexibility on protein recognition and binding. PMID- 1737039 TI - Rates of spontaneous exchange of synthetic radiolabeled sterols between lipid vesicles. AB - 14C-labeled sterols with structural variation in the polar function [3 alpha-OH, 3-O(CH2)2O-(CH2)2O(CH2)2OH, 3 alpha-NH2, 3 beta-NH2, and 3-OC(O)CHN = N] and at the 7 position (7-oxo, 7 alpha-OH, and 7 beta-OH) were synthesized and incorporated into unilamellar vesicles for studies of the rates of transfer to an excess of acceptor vesicles. Cholesterol, cholestanol, and epicholesterol underwent full exchange in a single kinetic pool, and 90% of the 3 alpha triethoxycholesterol was exchangeable in one pool. Biphasic kinetics with full exchangeability were observed for cholesterylamines, which bear a positive charge at the 3 position; the slow phase reflects the high activation energy for inner to-outer leaflet movement of the charged lipid. Biphasic kinetics were also found for cholesteryl diazoacetate, indicating that this photoaffinity probe and cholesterol have different mechanisms of transfer. Sterols that are more hydrophilic than cholesterol as estimated by reversed-phase high-performance chromatography (elution with acetonitrile-2-propanol, 4:1 v/v, with varying proportions of water) gave faster exchange rates than cholesterol, whereas sterols that are more hydrophobic gave slower exchange rates. However, the rates of [14C]sterol desorption from the lipid-water interface are not correlated with the relative sterol hydrophobicity as estimated by the logarithm of the capacity factors using acetonitrile-2-propanol-water as the mobile phase. These studies suggest that the interaction of sterols with phospholipids provides the principal physical-chemical basis for determining the rates of spontaneous exchange of sterols between bilayers. PMID- 1737040 TI - Raman spectroscopic study of semisynthetic species of cerebroside sulfate: two types of hydrocarbon chain interdigitation. AB - Raman spectroscopy was used to study the phase behavior of several semisynthetic species of the acidic glycosphingolipid cerebroside sulfate (CBS) which occur in myelin. The C-H stretching mode region at 2800-3100 cm-1 of C18:0-CBS, C24:0-CBS, and C26:0-CBS, and the alpha-hydroxy fatty acid species C18:0h-CBS, was studied in the presence of 2 M Li+ and 2 M K+. Earlier studies have shown that K+ shields the negative charge on the sulfate more effectively than Li+, thus promoting intermolecular hydrogen-bonding interactions between the lipid molecules. Indeed, a novel broad background feature was present in the Raman spectra from 2900 to 3200 cm-1, which was attributed to O-H stretch associated with intermolecular hydrogen bonding between lipid hydroxyl groups. After subtraction of this broad feature, the intensities of the lipid C-H stretching vibrational transitions could be determined. These indicated that in K+, the degree of order (intrachain conformation and lateral chain-chain interactions) of C18:0-CBS, whose hydrocarbon region is fairly symmetrical in chain length, is similar to that of the symmetric chain length glycerolipid dipalmitoylphosphatidylcholine, while the degree of order is lower in Li+, as a result of the increased lateral charge repulsion of the head groups in Li+. Two phase transitions were observed for the highly asymmetric species C24:0-CBS and C26:0-CBS in K+ but only one transition in Li+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737041 TI - Role of carbohydrate modification in the production and secretion of human granulocyte macrophage colony-stimulating factor in genetically engineered and normal mesenchymal cells. AB - Colony-stimulating factors (CSFs) are a group of acidic glycoproteins which stimulate the proliferation and differentiation of hematopoietic progenitor cells in vitro and stimulate hemopoiesis in vivo. Human GM-CSF contains two N-linked carbohydrate side chains of the complex acidic type and several sites of O-linked carbohydrate clustered on serine and threonine residues near the N-terminus of the molecule. Previous studies have failed to detect a significant functional role for the carbohydrate modification characteristic of human GM-CSF. Using permanent cell lines and transient expression systems which produce moderate to high levels of native or carbohydrate-deficient forms of the growth factor, the role of carbohydrate modification in the biosynthesis and secretion of GM-CSF was studied. Unlike a number of other secreted glycoproteins, the transient time and secretory efficiency of several carbohydrate-deficient mutants of GM-CSF are indistinguishable from those of the native growth factor in BHK, 293, COS, and ldlD cells. Furthermore, normal human endothelial cells and fibroblasts, which normally produce the growth factor, can synthesize and secrete GM-CSF that lacks all forms of carbohydrate modification. These studies help to point out the range of roles played by carbohydrate modification in the biosynthesis, assembly, and secretion of glycoprotein hormones. PMID- 1737042 TI - DNA sequence of the yeast transketolase gene. AB - Transketolase (EC 2.2.1.1) is the enzyme that, together with aldolase, forms a reversible link between the glycolytic and pentose phosphate pathways. We have cloned and sequenced the transketolase gene from yeast (Saccharomyces cerevisiae). This is the first transketolase gene of the pentose phosphate shunt to be sequenced from any source. The molecular mass of the proposed translated protein is 73,976 daltons, in good agreement with the observed molecular mass of about 75,000 daltons. The 5'-nontranslated region of the gene is similar to other yeast genes. There is no evidence of 5'-splice junctions or branch points in the sequence. The 3'-nontranslated region contains the polyadenylation signal (AATAAA), 80 base pairs downstream from the termination codon. A high degree of homology is found between yeast transketolase and dihydroxyacetone synthase (formaldehyde transketolase) from the yeast Hansenula polymorpha. The overall sequence identity between these two proteins is 37%, with four regions of much greater similarity. The regions from amino acid residues 98-131, 157-182, 410 433, and 474-489 have sequence identities of 74%, 66%, 83%, and 82%, respectively. One of these regions (157-182) includes a possible thiamin pyrophosphate (TPP) binding domain, and another (410-433) may contain the catalytic domain. PMID- 1737043 TI - Inhibition of the cation-induced reversible changes in excitation energy distribution in thylakoids of BASF 13.338-grown plants. AB - Measurements of relative quantum yields of Photosystem II and Photosystem I partial reactions and room-temperature chlorophyll a fluorescence of thylakoids in high- and low-salt media showed that the cation-induced changes in the excitation energy distribution were inhibited in the thylakoids isolated from pea plants grown in the presence of sublethal concentration of the pyridazinone herbicide BASF 13.338. Simultaneous measurement of Photosystem II and Photosystem I fluorescence emission kinetics at 77 K showed that the ability of cations to regulate excitation energy spillover from Photosystem II to Photosystem I was inhibited in thylakoids of the BASF-grown plants. Cation regulation of the absorption cross-section of the photosystems was not affected. Electron microscope data revealed that the proportion of stroma membranes relative to grana membranes was markedly less in the thylakoids of the BASF-grown plants. Furthermore, when the thylakoids were resuspended in low-salt medium, no unstacking of the grana was detected. The observed inhibition of cation-induced spillover change was presumably due to loss of ability of these photosynthetic membranes to undergo unstacking in low-salt medium. PMID- 1737044 TI - Effect of thermoinduced changes in T4 bacteriophage structure on the process of molecular recognition of 'host' cells. AB - By means of high-precision acoustic measurements and by methods of fluorescent and electron microscopy, investigations have been performed of thermoinduced conformational changes in T4 bacteriophage and its thermolabile mutants altered in baseplate proteins (gene products 7, 8, 10). A relationship was found between the conformational changes in T4 bacteriophage structure in the temperature range of 33-45 degrees C and the efficiency of bacteriophage adsorption and the changes in the orientation of long tail fibers. The possibility of heat regulation of 'recognition' of 'host' cells by bacterial viruses is suggested. PMID- 1737045 TI - Reaction rate with suspended lipase catalyst shows similar dependence on water activity in different organic solvents. AB - We have studied the effect of thermodynamic water activity (a W) on the initial rate of esterification catalysed by an immobilised lipase (Lipozyme) suspended in an organic reaction mixture. The catalyst and the organic phase were separately pre-equilibrated to the same aw value. The rate shows similar dependence on aw in reaction mixtures based on five different organic solvents ranging in polarity from pentan-3-one to hexane, and in a liquid reactant mixture. There is a maximum at aw about 0.5, with a decline to 30-70% at aw of either 0.9 or less than 0.01. When the rates are presented in terms of water concentration in the organic phase (or total water content of the system), the maxima for the various solvents come at very different positions, reflecting the widely varying solubilities of water in the organic phase. PMID- 1737046 TI - Proteinase-catalyzed activation of porcine heart muscle pyruvate dehydrogenase and identification of its cleavage site. AB - Porcine heart muscle pyruvate dehydrogenase (PDH, EC 1.2.4.1) with subunit composition alpha 2 beta 2 catalyzes the initial decarboxylation step of an oxidative decarboxylation sequence of pyruvate. Highly purified PDH, was further activated several-fold by limited digestion with trypsin, Staphylococcus aureus V8 proteinase (V8) or papain. The activation with these proteinases required about 10 min to attain a maximal level, lasted 1/2-2 h and thereafter decreased gradually. Addition of an inhibitor of each proteinase resulted in an immediate cessation of any further changes in the enzymatic activity. The optimal pH of the proteinase-activated PDH was not affected. Proteinases increased the maximum velocity and the apparent Km values for pyruvate, but the Hill coefficients for pyruvate were unchanged. Proteinase-activated PDH was capable of associating two other component enzymes to produce large unit resembling the native complex. The Coomassie brilliant blue stained gels after SDS-PAGE showed that the PDH alpha subunit (41 kDa) was cleaved by trypsin or V8 into two major fragments (31 and 10 kDa), whereas PDH beta was unaffected. By amino-terminal sequence analyses of these fragments the trypsin cleavage sites were identified as Arg-273 and Arg-282 and the V8 cleavage sites were Glu-277 and Glu-280. PMID- 1737047 TI - Isolation of a 5-hydroxybenzimidazolyl cobamide-containing enzyme involved in the methyltetrahydromethanopterin: coenzyme M methyltransferase reaction in Methanobacterium thermoautotrophicum. AB - Formaldehyde conversion into methyl-coenzyme M involves (a) reaction of the substrate with 5,6,7,8-tetrahydromethanopterin (H4MPT) giving 5,10-methylene H4MPT, followed by its reduction to 5-methyl-H4MPT and (b) transfer of the methyl group from the latter compound to coenzyme M. The reactions were studied in a resolved system from Methanobacterium thermoautotrophicum strain delta H. The first part (a) of the reactions was catalyzed by the 55% ammonium sulfate supernatant of cell-free extracts. The methyltransferase step (b) was dependent on an oxygen-sensitive enzyme, called methyltransferase a (MTa). Isolation of MTa was achieved by gel filtration on Sephacryl S-400. MTa was a high-molecular weight complex of at least 2000 kDa and between 900 to 1500 kDa when purified in the absence and presence of the detergent CHAPS, respectively. The enzyme consisted of 100 kDa units composed of three subunits in an alpha beta gamma configuration with apparent molecular masses of 35, 33 and 31 kDa, respectively. The corrinoid, 5-hydroxybenzymidazolyl cobamide (B12HBI, Factor III) copurified with MTa and the latter contained 2 nmol B12HBI per mg protein. B12HBI present in MTa could be methylated under the appropriate conditions by 5-methyl-H4MPT. These findings suggest that the corrinoid is a prosthetic group of MTa. MTa may be homologous to the corrinoid membrane protein purified before from M. thermoautotrophicum strain Marburg (Schulz, H., Albracht, S.P.J., Coremans, J.M.C.C. and Fuchs, G. (1988) Eur. J. Biochem. 171, 589-597). PMID- 1737048 TI - The major plasma kallikrein inhibitor of guinea pig plasma. AB - A plasma kallikrein inhibitor in guinea pig plasma (KIP) was purified to homogeneity. KIP is a single chain protein and the apparent molecular weight is estimated to be 59,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In amino acid composition, KIP is similar to human and mouse alpha 1-proteinase inhibitors and mouse contrapsin. KIP forms an equimolar complex with plasma kallikrein in a dose- and time-dependent fashion. The association rate constants for the inhibition of guinea pig plasma kallikrein by KIP, alpha 2-macroglobulin, C1-inactivator and antithrombin III were 2.5 +/- 0.3.10(4), 2.4 +/- 0.4.10(4), 6.6 +/- 0.5.10(4) and 9.1 +/- 0.6.10(2), respectively. Comparison of the association rate constants and the normal plasma concentrations of the four inhibitors demonstrates that KIP is ten-times as effective as alpha 2-MG and other two inhibitors are marginally effective in the inhibition of kallikrein. KIP inhibits trypsin and elastase rapidly, and thrombin and plasmin slowly, but is inactive for chymotrypsin and gland kallikrein. These results suggest that KIP is the major kallikrein inhibitor in guinea pig plasma and the proteinase inhibitory spectrum is unique to KIP in spite of the molecular similarity to alpha 1-proteinase inhibitor. PMID- 1737049 TI - Subtilisin from Bacillus subtilis strain 72. The influence of substrate structure, temperature and pH on catalytic properties. AB - Kinetic constants for the hydrolysis of the series of p-nitroanilide peptide substrates catalyzed by subtilisin from Bacillus subtilis strain 72 have been determined. The series of N-protected p-nitroanilides of the Z-A2-A1-pNA, Z-A3-A2 A1-pNA, Z-A4-A3-A2-A1-pNA types (Z-, benzyloxycarbonyl-1; -pNA, p-nitroanilide; A1-An, amino acid residues of the L-configuration) have been used. Subsite S1 reveals a preference for hydrophobic amino acid residues, i.e., leucine and phenylalanine. A preference for Leu over Phe at this position is manifested at the catalytic step, but not during the binding process. The beta-branched (Val, Ile) and the basic (Arg) amino acid residues cannot interact with the S1 subsite and the hydrolysis of the corresponding peptides occurs exclusively at the A2-A1 bond. If S1/A1 interactions are weak (Ala, Nva, Nle), the amino acid residue A1 can interact with subsites S1 and S'1 resulting in the hydrolysis at two bonds (A1-pNA and A2-A1). The data obtained suggests that the S'1 subsite is of broad selectivity. Subsite S2 reveals a preference for small amino acid residues. At pH 5.5-9 and below 50 degrees C, the subtilisin study does not lose its activity. At higher temperatures a rapid thermoinactivation occurs. Substrate binding stabilizes the enzyme. The temperature dependences of the kinetic and thermodynamic parameters suggest that the enzyme exists in two, i.e., 'cold' and 'hot' forms. At 22 degrees C the 'cold' form turns into the 'hot' one possibly owing to a conformational change. The enzyme-substrate complex does not exhibit such behavior and exists in only one form in the whole temperature range studied. The activity of an uncomplexed enzyme is controlled by a group of pKa = 7.2 +/- 0.1, which probably belongs to the histidine imidazole. PMID- 1737050 TI - Phosphorylation of the cardiac isoform of calsequestrin in cultured rat myotubes and rat skeletal muscle. AB - Calsequestrin is a high-capacity Ca(2+)-binding protein and a major constituent of the sarcoplasmic reticulum (SR) of both skeletal and cardiac muscle. Two isoforms of calsequestrin, cardiac and skeletal muscle forms, have been described which are products of separate genes. Purified forms of the two prototypical calsequestrin isoforms, dog cardiac and rabbit fast-twitch skeletal muscle calsequestrins, serve as excellent substrates for casein kinase II and are phosphorylated on distinct sites (Cala, S.E. and Jones, L.R. (1991) J. Biol. Chem 266, 391-398). Dog cardiac calsequestrin is phosphorylated at a 50 to 100-fold greater rate than is rabbit skeletal muscle calsequestrin, and only the dog cardiac isoform contains endogenous Pi on casein kinase II phosphorylation sites. In this study, we identified and examined both calsequestrin isoforms in rat muscle cultures and homogenates to demonstrate that the cardiac isoform of calsequestrin in rat skeletal muscle was phosphorylated in vivo on sites which are phosphorylated by casein kinase II in vitro. Phosphorylation of rat skeletal muscle calsequestrin was not detected. In tissue homogenates, cardiac and skeletal muscle calsequestrin isoforms were both found to be prominent substrates for endogenous casein kinase II activity with cardiac calsequestrin the preferred substrate. In addition, these studies revealed that the cardiac isoform of calsequestrin was the predominant form expressed in skeletal muscle of fetal rats and cultured myotubes. PMID- 1737051 TI - Circular dichroism of cysteine proteinases from papaya latex. Evidence of differences in the folding of their polypeptide chains. AB - Two forms of proteinase omega were isolated from a commercial preparation of chymopapain (EC 3.4.22.6) by means of cation-exchange liquid chromatography. Their circular dichroism (CD) spectra in the 182-320 nm region indicated that the two forms possess closely related structures. For comparison, we also recorded the CD spectra of chromatographically purified samples of papain (EC 3.422.2) and the most abundant form of chymopapain. According to the qualitative criteria proposed by Manavalan and Johnson (1983) Nature 305, 831-832), the spectral characteristics of papain correctly indicate that this protein belongs to the alpha + beta class. Proteinase omega is also placed in the alpha + beta category, while chymopapain seems to be an alpha/beta protein. Quantitative estimation of secondary structures yielded contents of helices and parallel beta-sheet that were higher in the case of chymopapain. Thus, the results of this work suggest that there are some differences in the folding pattern of chymopapain with respect to the other two proteinases. This proposal seems unexpected when the high amino acid sequence identity among these enzymes is considered. PMID- 1737052 TI - An enzyme immunoassay and immunoblot analysis for curculin, a new type of taste modifying protein: cross-reactivity of curculin and miraculin to both antibodies. AB - We have developed an enzyme immunoassay method for curculin, a new type of taste modifying protein. This method can accurately quantify 0.05-20 ng of curculin, a sensitivity about 3000-times that of the psychometric method. The content of curculin in the fruit of Curculigo latifolia increased gradually until 3 weeks after artificial pollination and dramatically at 4 weeks, to finally reach 1.3 mg per fruit. Immunoblot analysis indicated that antiserum to curculin was faintly reactive with miraculin, but not with thaumatin or monellin. PMID- 1737053 TI - Inactivation of wheat-germ aspartate transcarbamoylase by the triazinyl dye, procion red HE3B. AB - Aspartate transcarbamoylase from wheat germ is irreversibly inactivated by the triazinyl dye Procion Red HE3B. Since triazinyl dyes may mimic nucleotides, and UMP is a known allosteric modifier of this enzyme, the reaction was studied to elucidate whether the dye is an 'affinity label' for the enzyme. The reaction is apparently first order in the first 5-10 min, but is more complex in the longer term and does not go to completion. Kinetic analysis of the initial phase suggests that there are two parallel reactions, one saturable (dye binds reversibly before reaction) and one non-saturable (biomolecular). The apparent rate constant kapp (i.e. the sum of the rate constants for the parallel reactions) varies only slightly over the pH range 7-10. In the presence of a number of active centre ligands, as well as the allosteric ligand UMP, there is a clear increase in kapp. This finding is contrary to the reduction in rate of inactivation (protection) normally provided by ligands against active-site directed reagents, suggesting that in the saturable reaction, there is a conformational change upon dye-binding that increases the exposure of the essential residue(s) with which the dye reacts. These results show that, although it probably inactivates by reaction with specific amino-acid residues, the dye is not bound at the substrate-binding or allosteric sites, i.e. it is not an affinity-labeling reagent in the usual sense. PMID- 1737054 TI - Fluorescence properties of native and photooxidised proteinase K: the X-ray model in the region of the two tryptophans. AB - The fluorescence properties of proteinase K are described and related to the X ray model refined at 1.48 A resolution. Upon excitation of proteinase K at 295 nm the fluorescence is determined by the two tryptophan residues, Trp-8 and Trp-212. The tryptophans are partly buried just below the surface of the molecule. Neither Trp is in a highly hydrophobic environment, suggesting that this cannot be the explanation for the fluorescence at 330 nm: formation of exiplexes with adjacent peptide bonds would seem to be the more likely cause. Trp-8 is located in a 'cavity', close to an internal cluster of water molecules. The contribution of Trp-8 to the total indole emission is 60% and that of Trp-212 is 40%. The tryptophan fluorescence quantum yield is constant in the pH range 3-9. The fluorescence spectrum resulting from the simultaneous excitation of the tyrosyl and tryptophyl residues at 280 nm is dominated by the indole fluorophores: 61% of the light absorbed by the tyrosyl side chains is transferred to the two indole rings. Iodide and caesium are not efficient quenchers of the proteinase K tryptophan fluorescence, which is explained by restricted access of the ions to the somewhat buried Trp side chains and by electrostatic repulsion of caesium ions. Acrylamide quenching proceeds via both a dynamic and a static process and the data show homogeneity of the indole fluorescence arising from fluorophores in similar environments. The activation energy for the thermal deactivation of the excited tryptophans is 54 kJ mol-1. This value is substantially higher than those found for other proteinases from microorganisms and arises from the thermostability of proteinase K. Photooxidation of proteinase K in the presence of proflavine follows the kinetics of a first order reaction. The two tryptophans differ in their photoreactivity, Trp-212 being considerably more reactive. PMID- 1737055 TI - Comparison of characteristics of bovine aromatic L-amino acid decarboxylase with human enzyme. AB - Aromatic L-amino acid decarboxylase (AADC) was purified from bovine adrenal medulla and properties of this enzyme were compared with those of AADC from human pheochromocytoma. The molecular weights of the subunits were identical between human and bovine enzymes and estimated to be 50,000 by SDS-polyacrylamide gel electrophoresis. An isoelectric point of the human enzyme was 5.7, while the bovine enzyme showed several distinct bands at the region of pH 4.9-5.3 in the absence of urea. Multiplicity of the isoelectric point of bovine AADC disappeared in the presence of urea. These results showed that there were some differences between the properties of human and bovine AADC in spite of the high homology (88%) in their primary structures. PMID- 1737056 TI - Effect of iron and retinoic acid on the control of transferrin receptor and ferritin in the human promonocytic cell line U937. AB - The effect of changes in iron availability and induction of differentiation on transferrin receptor expression and ferritin levels has been examined in the promonocytic cell line U937. Addition of iron (as 200 micrograms/ml saturated transferrin) or retinoic acid (1 microM) both caused approx. 70% reduction in the average number of surface transferrin receptors, while the iron chelator desferrioxamine caused an 84% increase. Comparable changes also occurred in the levels of transferrin receptor mRNA. Neither iron nor retinoic acid significantly altered the half-life of transferrin receptor mRNA in the presence of actinomycin D (approx. 75 min) but a 10-fold increase in stability occurred in the presence of desferrioxamine. Iron and retinoic acid both caused an increase in intracellular ferritin levels (approx. 4-and 3-fold, respectively), while desferrioxamine reduced ferritin levels by approx. two-thirds. The effect of iron and retinoic acid added together did not differ greatly from that of each agent alone. None of the treatments greatly affected levels of L-ferritin mRNA. Virtually no H-ferritin mRNA was detected in U937 cells. These results show that changes in ferritin and transferrin receptor caused by treatment with retinoic acid are similar to those induced by excess iron, and suggest that changes in these proteins during cell differentiation are due to redistribution of intracellular iron into the regulatory pool(s), rather than to iron-independent mechanisms. PMID- 1737057 TI - Urinary excretion of thromboxane and prostacyclin metabolites during chronic low dose aspirin: evidence for an extrarenal origin of urinary thromboxane B2 and 6 keto-prostaglandin F1 alpha in healthy subjects. AB - In vivo biosynthesis of thromboxane and prostacyclin is currently evaluated by measuring urinary excretion of selected metabolites. Urinary thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (non-enzymatic hydrolysis products of thromboxane and prostacyclin) are thought to derive from renal biosynthesis of the parent compounds, while enzymatic metabolites such as 2,3-dinor-TXB2 and 2,3-dinor-6-keto-PGF1 alpha appear to be mainly derived from systemic (platelet) thromboxane and (vascular) prostacyclin, respectively. Using immunoaffinity extraction and high-resolution gas chromatography-negative ion chemical ionization mass spectrometry (HRGC-NICIMS), we measured the paired excretion of non-enzymatic and enzymatic metabolites of thromboxane and prostacyclin in healthy subjects before, during and after an eight-day schedule of oral low-dose aspirin (30 mg/day), a treatment known to inhibit platelet and perhaps vascular but not renal cyclooxygenase. Low-dose aspirin cumulatively reduced urinary excretion of TXB2 and 2,3-dinor-TXB2 (about 80% inhibition on day 8 of aspirin treatment, P less than 0.01), as well as 6-keto-PGF1 alpha and 2,3 dinor-6-keto-PGF1 alpha (about 45% inhibition on day 8 of aspirin treatment, P less than 0.01). Excretion of all metabolites recovered slowly after aspirin withdrawal. Urinary PGE2, taken as an index of renal cyclooxygenase activity, was not inhibited by aspirin. A highly significant correlation was found between paired excretion values of non-enzymatic vs. enzymatic metabolites of thromboxane and prostacyclin in all individuals studied (TXB2 vs. 2,3-dinor-TXB2 (r = 0.91 +/ 0.03); 6-keto-PGF1 alpha vs. 2,3-dinor-6-keto-PGF1 alpha (r = 0.92 +/- 0.06], irrespective of aspirin treatment. TXB2/2,3-dinor-TXB2 and 6-keto-PGF1 alpha/2,3 dinor-6-keto-PGF1 alpha mean ratios remained unchanged throughout the experiment. These data do not support the view that urinary TXB2 and 6-keto-PGF1 alpha derive mainly from renal biosynthesis in healthy subjects, but rather suggest that they may represent a fraction of systemic (platelet) thromboxane and (vascular) prostacyclin escaping metabolism. These data also suggest that chronic low-dose aspirin may partly inhibit vascular prostacyclin in addition to platelet thromboxane biosynthesis. PMID- 1737058 TI - Selective inhibition of the synthesis of phosphoenolpyruvate carboxykinase in freshly isolated proximal tubule cells. AB - The behaviour of renal phosphoenolpyruvate carboxykinase (PEPCK) in non-growing kidney cell suspension culture was investigated. In heterogeneous kidney cells, glomeruli-proximal tubule mixtures and purified proximal tubule fragments, the enzyme activity fell with a t1/2 of 3.3 h. Hormonal additions did not modify the process. The fall was also observed in cells prepared from animals preinduced with dexamethasone. The in vitro response of PEPCK is tissue specific. The decline was not the result of a decrease in cell viability, enzyme leakage nor due to the mitochondrial translocation of cytosolic PEPCK. The response observed is due to the selective inhibition of the synthesis of the enzyme and its destruction by non-lysosomal mechanisms. Acute and chronic acidification do not affect PEPCK activity. However, the degradation of PEPCK is temperature dependent and is greatly accelerated by glutathione. PMID- 1737059 TI - Effects of anti-oxidants on ornithine decarboxylase in mitogenically-activated T lymphocytes. AB - Reactive oxygen species formation is an early event following lymphocyte activation and may trigger other biochemical processes. Anti-oxidants (desferrioxamine (DES), nordihydroguaiaretic acid (NDGA) and potassium ferricyanide) inhibit human and murine T cell proliferation in vitro. Since an increase in ornithine decarboxylase (ODC) activity is an essential concomitant of T lymphocyte proliferation, we have examined in vitro the effects of anti oxidants on this activity increase. ODC activity in mouse lymph node T cells increased steadily from 6-24 h after addition of concanavalin A. The combination of phorbol myristate acetate (PMA) and ionomycin also stimulated ODC activity in these cells. The anti-oxidants DES, NDGA and ferricyanide strongly inhibited the increase in ODC activity seen in response to either concanavalin A or PMA/ionomycin. Dose-response curves for the inhibitory effects of the anti oxidants on DNA synthesis and ODC activity at 48 h after mitogen addition were very similar. Addition of putrescine or spermidine (10-100 microM) could not overcome the block in DNA synthesis induced by DES. Although the anti-oxidants inhibited the ODC activity increase in mitogen-stimulated T cells, they did not decrease mRNA levels for the enzyme. These results suggest that intracellular formation of reactive oxygen species is involved in the induction of ODC activity by a mechanism exerted at a posttranscriptional stage. The anti-oxidants can be employed as tools to elucidate contingent relationships between some intracellular events that follow T cell activation. PMID- 1737060 TI - Efflux and accumulation of amino nitrogen in relation to the volume of rat renal inner medullary cells exposed to media of variable osmolality. AB - The rate of efflux of 2-amino[14C]isobutyric acid (AIB) from pre-loaded slices of rat renal inner medulla has been followed during incubation in media whose osmolality was varied between 350 and 2500 mosmol/kg H2O by adjustment of NaCl and urea concentrations. Efflux was biphasic, and it was assumed that the second, slower phase represented mainly cellular loss of AIB. As a function of cell volume (water content) the mean net rate of 2nd phase efflux declined far more abruptly (-36%) during an increase in external osmolality from 350 to 720 mosmol/kg than during further increase to 2500 mosmol/kg, over which range the rate of efflux fell by only a further 12%. Conversely, relative decrements of steady-state cell water contents during these two transitions were -17% and -37%, respectively. It is probable that in strongly hyperosmolal media (above 720 mosmol/kg) reduction in the rate of amino acid catabolism, with resultant cellular accumulation, becomes more important than passive efflux as a determinant of cell amino nitrogen content, and that this is caused by the enzyme destabilizing effect of high intracellular concentrations of permeant urea. This interpretation is supported by the finding in the present study that trimethylamine N-oxide, which is known to counteract the destabilizing effect of urea, completely inhibited the accumulation of amino nitrogen (ninhydrin-positive substances) in media stronger than 720 mosmol/kg, as well as leading to further reduction of steady-state cell water contents, but was without effect on either variable in more dilute media. It is proposed that, under the conditions of this investigation, amino acids contribute to cell volume maintenance mainly by efflux and by metabolic accumulation under mildly and strongly hyperosmolal conditions, respectively, and that this interpretation is consistent with recent findings on the fluctuations in medullary levels of Na+, urea and total amino nitrogen in the intact kidneys of rats during acute water diuresis and oliguria (Law, R.O. (1991) Pflugers Arch. 418, 442-446). PMID- 1737061 TI - Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. AB - Necrosis and apoptosis are two distinct modes of cell death which differ in morphology, mechanism and incidence. Membrane disruptants, respiratory poisons and hypoxia cause ATP depletion, metabolic collapse, cell swelling and rupture leading to inflammation. These are typical features of necrosis. Apoptosis plays a crucial role in embryogenesis and development and is also prevalent in tumours. It is characterised by cell shrinkage, chromatin condensation and systematic DNA cleavage. Apoptotic cells are rapidly engulfed by phagocytes, thus preventing inflammatory reaction to degradative cell contents. In vivo, apoptosis is almost impossible to quantify due to problems of heterogeneity and the short half-life of an apoptotic cell. In vitro, mechanistic studies are further complicated by a late phase of apoptosis where the cell membrane becomes permeable to vital dyes and which occurs in the absence of phagocytes. Here we describe a novel and rapid multiparameter flow cytometric assay which discriminates and quantifies viable, apoptotic and necrotic cells via measurement of forward and side light scatter (proportional to cell diameter and internal granularity, respectively) and the DNA-binding fluorophores Hoechst 33342 and propidium. It is anticipated that mechanistic studies of apoptosis in a variety of cell types will greatly benefit from this mode of analysis. PMID- 1737062 TI - Red cell filterability determined using the cell transit time analyzer (CTTA): effects of ATP depletion and changes in calcium concentration. AB - Cell transit time analysis (CTTA) is a new filtrometric technique for assessing red blood cell deformability by measuring the conductivity change caused by passage of erythrocytes through a polycarbonate filter. Most reported studies to date using CTTA have focused on the transit time (TT), the duration of passage of an individual red cell through a micropore. Bulk flow rate has not been previously measured via CTTA. The use of new enzyme based cleaning solutions make it possible to reduce clogging in micropore filters. Therefore, valid measures of the number of red cell transits per unit time (counts/s: C/S) can now be obtained. We evaluated both parameters, TT and C/S, as indicators of red cell filterability. Our goal was to evaluate the effect of metabolic changes shown by alternative techniques to affect red cell deformability. The two best established factors are changes in intracellular [ATP] and [Ca2+]. ATP depletion produces a very small increase in TT but a very marked decrease in C/S. In contrast, the addition of low concentrations of calcium produces an increase in TT with minimal decrease in C/S. The effects of calcium appear to be complex. The substantial changes in intracellular calcium induced by the ionophore A23187 result in a curvilinear pattern of increase in transit times and reduction in counts per s. Lanthanum, which inhibits egress of intracellular calcium, causes an increase in TT with a drop in C/S. We conclude that CTTA demonstrates the same changes in red cell deformability measurable by alternative filtrometric techniques; however, CTTA furnishes two separate and independent parameters which may be used to evaluate red cell deformability. PMID- 1737063 TI - Potentiation of epidermal growth factor receptor protein-tyrosine kinase activity by sulfate. AB - The protein-tyrosine kinase activity of the epidermal growth factor (EGF) receptor is critical for EGF-stimulated cell growth, although little is known about the molecular details of its enzymatic activity. Previous studies have found that EGF receptor kinase activity can be stimulated by factors such as ammonium sulfate ((NH4)2SO4), but the manner in which (NH4)2SO4 induces this effect is unclear. Therefore, we have explored the processes by which (NH4)2SO4 potentiated tyrosine kinase activity to better understand not only the molecular events involved in (NH4)2SO4 activation, but also the kinetic properties and mechanism of the EGF receptor. In this study, the addition of an optimum concentration of (NH4)2SO4 (250 mM) resulted in a 5-fold stimulation of kinase activity toward the peptide substrate, angiotensin II. The sulfate group is primarily involved in this action, since other salts containing SO4(2-) increased kinase activity similarly, whereas salts containing Cl- and F- had less of an effect, and divalent salts such as HPO4(2-) and NaVO4(2-) were inhibitory at doses of 1 mM or more. In addition, EGF receptor kinase activation by (NH4)2SO4 did not strictly correlate with changes in the ionic strength or conductivity of the solution. However, several lines of evidence suggest that SO4(2-) directly alters the kinetic properties of the EGF receptor kinase: (1) the maximum velocity (Vmax) and Km (ATP) for EGF receptor phosphorylation of angiotensin II were substantially higher in the presence of (NH4)2SO4. (2) EGF receptor kinase activity in the absence of (NH4)2SO4 required either Mn2+ or Mg2+, yet in the presence of (NH4)2SO4, only Mn2+ supported the increase in kinase activity. (3) Ammonium sulfate addition altered the product inhibition pattern of ADP versus angiotensin II, suggesting that an enzyme-angiotensin II-ADP complex can form in the presence of (NH4)2SO4 but not in its absence. (4) The near-maximal rate of self-phosphorylation was not affected by (NH4)2SO4 but the apparent Km (ATP) was greatly increased. From these results, we propose a model for (NH4)2SO4 stimulation of EGF receptor kinase activity in which SO4(2-) interacts directly with the receptor or receptor-Mn(2+)-ATP complex and alters reactant binding and the catalytic efficiency of the tyrosine kinase. PMID- 1737064 TI - Ethanol is a potent stimulator of phosphatidylcholine breakdown in cultured rat hepatocytes. AB - Addition of ethanol (17 to 340 mM) to cultured rat hepatocytes stimulated the breakdown of phosphatidylcholine phospholipases D and C as measured by an increase in the rate of release of choline and phosphocholine into the medium. The effects of ethanol were mimicked by propanol, dimethylsulfoxide and to a lesser extent methanol. The magnitude of the stimulation seen with ethanol was equivalent to and additive to that produced by glucagon vasopressin, norepinephrine, A23187 or PMA. In contrast, ethanol (340 mM) stimulated PI specific phospholipase C activity by less than 20%. An equivalent stimulation of PC-specific phospholipase D and C was seen with as little as 20 mM ethanol and a 100% increase was seen with 340 mM ethanol. Ethanol did not significantly affect the ability of vasopressin, norepinephrine, ATP or A23187 to stimulate PI specific phospholipase C. It is concluded that while ethanol is only a weak stimulator of PI-specific phospholipase C, it is a potent stimulator of phosphatidylcholine breakdown in rat hepatocytes. PMID- 1737065 TI - Peroxide-metabolizing systems of the crystalline lens. AB - The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens. PMID- 1737066 TI - Niemann-Pick type II fibroblasts exhibit impaired cholesterol esterification in response to sphingomyelin hydrolysis. AB - Fibroblasts from patients with Niemann-Pick Type II disease, including the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) forms, exhibit reduced or delayed stimulation of cholesterol esterification by low density lipoprotein (LDL). Based on recent evidence that cholesterol esterification can also be stimulated by cell surface sphingomyelin hydrolysis, we have compared the response of normal, NPC and NPD fibroblasts to treatment with exogenous sphingomyelinase (SMase). Staphylococcus aureus SMase (greater than 0.05 U/ml) hydrolyzed over 90% of endogenous sphingomyelin within 1 h and increased incorporation of [3H]oleic acid into cholesterol-[3H]oleate after an initial lag in all three cell types. However, normal levels of cholesterol esterification were not observed for NP Type II fibroblasts: four NPD cell lines exhibited an average of 32% of normal response while cholesterol esterification was only 20% in two well-characterized NPC lines. A third NPC line exhibited normal response to SMase despite greater than 90% impairment of LDL-stimulated cholesterol esterification. Incubation of fibroblasts with LDL followed by SMase produced a synergistic response, particularly in NPC cells where there was little response to either treatment alone. Chloroquine abolished LDL-stimulated cholesterol esterification in normal fibroblasts but had no effect on the response to SMase, indicating that lysosomal enzymes may not be involved in SMase-mediated cholesterol esterification. These results suggest that intracellular processing of cholesterol derived from either LDL or release from the plasma membrane (by sphingomyelin hydrolysis) is affected in Niemann-Pick Type II cells and that these pathways can complement one another in the stimulation of cholesterol esterification. PMID- 1737067 TI - A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127. AB - We have identified a hitherto unknown genetic polymorphism of apolipoprotein A-IV (apoA-IV). The molecular basis for this polymorphism is an A to G substitution at nucleotide 1687 resulting in an Asn to Ser change of amino acid 127. The frequencies of the two apoA-IV alleles (designated apoA-IV127Asn and apoA IV127Ser), determined by Hin c II restriction analysis of PCR amplified exon three of the apoA-IV gene, were 0.788 and 0.212, respectively, in a Finnish population sample. Allele frequencies of another polymorphism due to a Thr to Ser substitution at amino acid 347 were determined using Hinf I restriction analysis. The allele frequencies were 0.823 for apoA-IV347Thr and 0.177 for apoA-IV347Ser. None of the apoA-IV polymorphisms (apoA-IV127:Asn----Ser, apoA-IV347:Thr----Ser and apoA-IV360:Gln----His) had any effect on plasma lipid and lipoprotein concentrations in cohorts of dyslipidemic men and in a population sample of normolipidemic controls. There was also no association between the history of previous myocardial infarction and any of the apoA-IV alleles. PMID- 1737068 TI - Large deletion of androsterone UDP-glucuronosyltransferase gene in the inherited deficient strain of Wistar rats. AB - LA Wistar rats have a deficiency of androsterone UDP-glucuronosyltransferase (UDPGT) and are present in Wistar rat colonies around the world. In order to clarify the molecular mechanism of the deficiency, androsterone UDPGT cDNA clone, pGT2 was isolated from rat liver cDNA library and was digested with restriction enzymes to afford three probes for Northern and Southern blot analyses in HA (normal), heterozygous LA and LA Wistar rats. In Northern blot analysis, androsterone UDPGT mRNA was totally absent in LA Wistar rat liver. Southern blot analysis suggested a large deletion of androsterone UDPGT gene in the rats. Genomic DNA amplifications with synthetic primers which have nucleotide sequences corresponding to the 5'-region of androsterone UDPGT cDNA, suggested that androsterone UDPGT gene has exon 1 with a length of some 700 bp and that this exon is deleted in LA Wistar rats. Based on these lines of evidence, it is concluded that the large portion of androsterone UDPGT gene is deleted in LA Wistar rats, which results in the absence of androsterone UDPGT mRNA and consequently the corresponding enzyme protein. PMID- 1737069 TI - The validity of the cholesterol nucleation assay. AB - The validity of the cholesterol nucleation assay rests on the assumption that all cholesterol crystals are removed at the start of the assay so that de novo formation of crystals can be studied. In this paper we have tested the validity of this assumption. Cholesterol crystals were added to supersaturated model bile. Subsequently the mixtures were either filtered over a 0.22 micron filter or centrifuged at 37 degrees C for 2 h at 100,000 x g. After ultracentrifugation the isotropic interphase was collected. Using polarized light microscopy no crystals could be visualized in this fraction. However, the nucleation time of the isotropic interphase decreased from 6.8 +/- 1.1 days to 1.8 +/- 0.2 days (mean +/ S.E., P less than 0.01, n = 5) when 10-100 micrograms/ml crystals were added prior to centrifugation. Similar results were observed when instead of centrifugation the mixtures containing crystals were filtered. After filtration over a 0.22 micron filter no crystals could be detected in the filtrate. Yet the nucleation time of the filtrate decreased from 6.4 +/- 0.7 days to 3.1 +/- 0.5 days (mean +/- S.E.) when 10 micrograms/ml cholesterol crystals were added before filtration (n = 10, P less than 0.01). Since no cholesterol crystals could be detected at the start of the assay the reduction in nucleation time must have been brought about by cholesterol microcrystals that passed through the filter. Supplementation of cholesterol crystals to model bile did not accelerate the nucleation time when the samples were passed over a 0.02 micron filter, indicating that the size of the microcrystals was larger than 20 nm. The effect of addition of cholesterol crystals prior to filtration over a 0.22 micron filter was also tested in the crystal growth assay recently developed by Busch et al. ((1990) J. Lipid Res. 31, 1903-1909). Addition of crystals had only a minor effect on the assay. In conclusion, the reduced nucleation time of biles from gallstone patients is probably not only due to the presence of promoting or the absence of inhibiting proteins, but can be caused by the presence of small cholesterol crystals in these biles. PMID- 1737070 TI - The chemical characterization of melanin contained in substantia nigra of human brain. AB - The pigment of substantia nigra human brain has been extracted by a mild procedure consisting of washes with phosphate buffer, methanol and incubation with SDS-proteinase. Pyrolysis gas chromatography mass spectrometry, infrared spectrometry, termogravimetric analysis and elemental analysis were the techniques used for the chemical characterization. An indole moiety bound to a sulfur containing amino acid and to palmitic acid were the main aspects found in the structure. The presence of a 7% inorganic component was observed. This probably contains Fe, Cu, Zn and Cr which are also relevant, for the formation and the role of melanin in substantia nigra neurons. The fatty acid moiety is chemically bound to the indole structure as it was not eliminated by repeated methanol washing. The same situation occurs for the sulfur containing group. Considering these data and the most abundant molecules present in substantia nigra the precursor of neuromelanin seems to be a cysteinyl-catechol, to which is then bound a palmityl group. PMID- 1737071 TI - Expression of the mouse c-abl type IV proto-oncogene product in the insect cell baculovirus system. AB - The cellular gene c-abl is the normal homologue of the transforming gene (v-abl) within the genome of the Abelson leukaemia virus. The cDNA sequence coding for the cellular form of the murine abl gene (c-abl type IV) has been inserted into the baculovirus transfer vector, pAc36C, so that the c-abl gene is under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells infected with the recombinant transfer vector in the presence of wild type AcNPV DNA yielded recombinant, polyhedrin negative virus that expressed moderate levels of the c-Abl protein (representing approx. 0.5-1% of the stained cellular proteins as determined by densitometric scanning). The insect derived c-Abl protein was compared to the P210-BCR/ABL protein from K562 cells, a cell line derived from a patient with chronic myelogenous leukaemia. Antibodies raised against synthetic peptides based on c abl encoded peptides react with the insect derived c-Abl. In addition, the baculovirus derived c-Abl protein has a tyrosine kinase activity as demonstrated by phosphorylation of a synthetic polypeptide and also by autophosphorylation. Phosphoamino acid analysis of immunoprecipitated, autophosphorylated baculovirus derived c-Abl protein indicates that the majority of label incorporated is on the tyrosine residues. Immunofluorescence microscopy has been used to show that the majority of the c-Abl protein expressed in cells infected with recombinant virus is located in the nuclear and plasma membranes. PMID- 1737072 TI - Fatty acid beta-oxidation in leukocytes from control subjects and medium-chain acyl-CoA dehydrogenase deficient patients. AB - In recent years an increasing number of inherited diseases in man have been identified in which there is an impairment in mitochondrial fatty acid oxidation. Diagnosis is usually done by gas-chromatographic analysis of urine, which may give difficulties, since urinary abnormalities may only be present intermittently. We therefore studied whether leukocytes could be used to study mitochondrial beta-oxidation directly. The results described herein show that leukocytes are able to beta-oxidize octanoate and palmitate. Furthermore, clear abnormalities in octanoate beta-oxidation were found in leukocytes from patients with an established deficiency of medium-chain acyl-CoA dehydrogenase, suggesting that measurement of octanoate and palmitate beta-oxidation in leukocytes may contribute to rapid diagnosis of medium-chain acyl-CoA dehydrogenase deficiency and presumably other mitochondrial beta-oxidation disorders. PMID- 1737073 TI - The Atlantic gap: clinical trials in Europe and the United States. PMID- 1737074 TI - Controlled trial of bright light for nonseasonal major depressive disorders. AB - Psychotropic drug-free hospitalized veterans with nonseasonal major depressive disorders or depressed forms of bipolar disorder were treated with light for 1 week. Twenty-five patients were randomly assigned to bright white light treatment (2000-3000 lux), and 26 patients were randomized to dim red light placebo control treatment. Unlike those treated with dim red light, those treated with bright white light showed declines in three measures of depression during treatment. Partial relapse appeared within 2 days. A global depression score showed a statistically significant (p = 0.02) difference favoring bright white light treatment. Two bright-light-treated patients became mildly hypomanic, but side effects were mild. Improvement was not correlated with patient expectations; indeed, patients expected somewhat greater benefit from the placebo. Patients treated in summer responded as well as those treated in winter. Baseline electroencephalogram (EEG) sleep stage data (e.g., rapid eye movement; REM latency) did not predict treatment responses. These 1-week treatment results suggest that bright light might produce benefits for patients with nonseasonal depression. Bright light should not be recommended for routine clinical application before additional assessments with longer treatment durations are done. PMID- 1737075 TI - Noradrenergic function in panic disorder. Effects of intravenous clonidine pretreatment on lactate induced panic. AB - To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis. PMID- 1737076 TI - Characterization of a synaptic antigen of interest in neuropsychiatric illness. AB - Monoclonal antibodies exhibiting relative differences in binding to brain homogenates from diseased versus control brains may be useful probes into the molecular pathology of neuropsychiatric illness. To be of value, the antibodies must be useful in characterization of the antigens putatively involved in the illness. An antibody called EP10 showed some differences in binding to homogenates from a small sample of schizophrenia brains compared with controls. In the present study, the antigen for this antibody was characterized in control brains using quantitative, immunocytochemical, and biochemical techniques. The antigen is a 38,000 dalton synaptic vesicle protein, which is identical to synaptophysin by immunological criteria. However, the EP10 epitope is of interest, as this binding site does not appear to be present in rat or bovine synaptophysin. Brain regional studies using EP10 indicate that the antigen may be present in only a subset of synaptic terminals. Further studies are required to fully characterize the epitope, and to determine the significance of the earlier findings related to schizophrenia. PMID- 1737077 TI - Temporal lobe dysfunction and electrodermal nonresponding in schizophrenia. AB - The present study examined the biological correlates of electrodermal activity in 63 patients with DSM-III diagnosed chronic schizophrenia. Subjects were administered a battery of neuropsychological tests sensitive to temporal lobe, frontal lobe, and overall brain functioning. Brain morphology was evaluated by calculating the size of the lateral ventricles, measuring the width of the third ventricle, and rating the extent to which cortical sulci were visible. Electrodermal hyporesponsiveness was associated with impaired performance on tests that assessed temporal lobe functioning. No association was found between the brain morphology indices and electrodermal activity. PMID- 1737078 TI - Early return to REM sleep after nocturnal awakening in depression. AB - Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened from rapid eye movement (REM) sleep between 1:30 and 3:30 AM, and the rapidity of return to REM sleep was determined. The time it took to return to REM sleep was reduced in depressives compared with controls: 61.6 (17.9 SD) min versus 80.6 (24.9 SD) min, respectively (p = 0.01). The time elapsed until the return to REM sleep was significantly correlated with baseline REM latency in controls (but not depressives). In contrast, return to REM time was significantly correlated with depression severity scores in depressives (but not controls). There was no evidence to support the hypothesis that the more rapid return to REM sleep in depression was caused by a slow wave sleep deficit. The mechanism underlying the rapid return of REM sleep in depression thus may be related to a severity-linked disturbance, such as a proposed increase in REM "pressure." PMID- 1737079 TI - Paradoxical effects of adrenal steroids on the brain: protection versus degeneration. PMID- 1737080 TI - Effect of fluoxetine on plasma desipramine and 2-hydroxydesipramine. PMID- 1737081 TI - MRI, cerebral pathology, and schizophrenia. PMID- 1737082 TI - An IgE mechanism in autistic hypersensitivity? PMID- 1737083 TI - Depersonalization following nitrazepam withdrawal. PMID- 1737084 TI - The age of Karl Ludwig Kahlbaum. PMID- 1737085 TI - Phospholipase A2 in schizophrenia. PMID- 1737086 TI - Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma. AB - After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases. PMID- 1737087 TI - Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice. AB - The Philadelphia (Ph) translocation is responsible for the generation of the chimeric BCR/ABL oncogene. The Ph chromosome constitutes the earliest detectable chromosome abnormality in chronic myelogenous leukemia and is also found in acute lymphoblastic leukemia. Mice transgenic for a P190 BCR/ABL-producing DNA construct develop lymphoblastic leukemia/lymphoma and provide an opportunity to study early stages of the disease as well as progression. In this study, we have karyotyped the bone marrow of 10 19-day-old BCR/ABL P190 transgenic mice from a line that reproducibly develops leukemia/lymphoma. Leukemic cells from 17 terminally ill transgenic founders and progeny were also karyotyped as well as bone marrow transplant recipients of leukemic donor marrow. Karyotypically visible aberrations were absent from the early stages of BCR/ABL P190-generated leukemia and normal metaphases could be found even in the terminal stages of the disease. A high frequency of aneuploidy was found in advanced leukemia, with a marked preference for the gain of mouse chromosomes 12, 14, or 17. These results point to a primary role for BCR/ABL in leukemogenesis and suggest a destabilizing effect of the BCR/ABL gene on the regulation of cell division. PMID- 1737088 TI - High expression of transforming growth factor-beta long cell cycle times and a unique clustering of S-phase cells in patients with acute promyelocytic leukemia. AB - Expression of transforming growth factor-beta (TGF-beta), which inhibits the proliferation of hematopoietic progenitors, was investigated simultaneously with cell cycle characteristics in 63 bone marrow biopsies from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine (BrdU) was administered to every patient (17 newly diagnosed) for determination of the labeling index (LI) and the durations of S-phase (Ts) and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1% v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when compared with other French-American-British subtypes. TGF-beta expression (detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically high, especially in interstitial areas of the biopsies. S-phase cells were found as geographically restricted islands of proliferation (GRIPs) in 20 of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of 15. We conclude that the presence of high TGF-beta expression may explain the biologic basis for the slowly cycling nature of leukemic promyelocytes in APL as well as the unique clustering of S-phase cells observed in GRIPs. PMID- 1737089 TI - Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia. AB - The aim of the present work was to understand the pathophysiology of the severe human thalassemias as represented by beta-thalassemia intermedia and hemoglobin (Hb) H (alpha-thalassemia) disease. We have previously shown that the material properties of the red blood cell (RBC) and its membrane differ in severe alpha- and beta-thalassemia, and we now show that this difference is probably caused by accumulation of alpha-globin chains at the cytoskeleton in beta-thalassemia, whereas beta-globin chains are associated with the cytoskeleton in alpha thalassemia. In both alpha- and beta-thalassemia, some of these globin chains have become oxidized as evidenced by loss of the free thiols. Furthermore, there is similar evidence of oxidation of protein 4.1 in beta-thalassemia, whereas beta spectrin appears to be subject to oxidation in alpha-thalassemia. These observations support the idea that the association of partly oxidized globin chains with the cytoskeleton results in oxidation of adjacent skeletal proteins. The abnormality of protein 4.1 in beta-thalassemia is consistent with a prior observation, and is also in accord with the known importance of protein 4.1 in maintenance of membrane stability, a property that is abnormal in beta thalassemic membranes. PMID- 1737090 TI - Oxidative red blood cell membrane injury in the pathophysiology of severe mouse beta-thalassemia. AB - In severe human beta-thalassemia, the pathophysiology relates to accumulation of excess alpha-globin chains at the membrane. One hypothesis is that membrane associated alpha-globin by virtue of it's iron or hemichromes produces oxidation of adjacent membrane proteins. The availability of a mouse model of severe beta thalassemia, as well as a transgenic (thalassemic-sickle) mouse that expresses 12% of human beta s-chain, has allowed us to study the effect of graded accumulation of alpha-chains at the red blood cell (RBC) membrane on the clinical status of the animal and on the material properties of its RBCs. Proteins from control, beta-thalassemic, and transgenic mouse RBC membranes were analyzed for evidence of oxidation, as measured by thiol-disulfide exchange chromatography, which detects intramolecular sulfhydryl oxidation. Ratios of oxidized globin to protein 7 were calculated and increased amounts were seen in thalassemic mice as compared with control mice and transgenic mice. Furthermore, there were increased amounts of thiol-free protein 4.1 in the thalassemic mice, compared with very small amounts in the control mice and intermediate amounts in the transgenic mice. Membrane mechanical stability as assessed by ektacytometry showed that the thalassemic mouse RBCs were markedly unstable. Transgenic mouse RBCs showed intermediate levels of membrane instability compared with the controls. We propose that this oxidized globin, in conjunction with oxidized protein 4.1, accounts (at least in part) for membrane instability. A 12% increase in beta s globin chain synthesis (by decreasing excess globin available) confers considerable protection against both oxidative damage and the consequent membrane instability. PMID- 1737091 TI - Growth in children after bone marrow transplantation: busulfan plus cyclophosphamide versus cyclophosphamide plus total body irradiation. AB - Growth was assessed during the first and second years following bone marrow transplantation (BMT) in 47 children treated by either busulfan plus cyclophosphamide (BU/CY) (n = 24) or cyclophosphamide plus fractionated total body irradiation (CY/TBI) (n = 23). Before transplant, the median height was only 0.2 SD below age- and sex-adjusted means (range, -2.5 to +3.0). Height was greater than 2.0 SD below normal in only three patients (6%). The pretransplant heights were comparable in the BU/CY and CY/TBI groups (-0.1 v -0.6 SD, P = .35). Following transplant, median 1- and 2-year heights were 0.7 and 0.9 SD below normal, respectively. Growth rates were 2.2 SD and 1.4 SD below normal during the first and second years, respectively. Growth rates were greater than 2.0 SD below normal in 24 of 47 (51%) at 1 year and in 12 of 31 (39%) at 2 years after transplant. Growth rates in patients treated with BU/CY were comparable to those treated with CY/TBI during both years: -2.5 versus -1.7 SD during the first year (P = .19, Wilcoxon), and -1.5 versus -1.1 SD during the second year (P = .61). Growth rates during the second year correlated with growth rates during the first year (r = .36, P = .046). Growth rates during the first year were lower in patients who had been given prior cranial irradiation, those who were near pubertal age at the time of transplant, and those who were transplanted for a disease other than acute lymphoblastic leukemia (ALL). During the second year, poor rates of growth were associated only with the use of corticosteroids after transplant. PMID- 1737092 TI - Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique. AB - Prolonged disease-free survival of patients with recurrent or resistant non Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy. PMID- 1737093 TI - Nucleolar proteins B23 and C23 as target antigens in chronic graft-versus-host disease. AB - Previously we observed that sera from recipients of allogeneic bone marrow transplants who developed extensive chronic graft-versus-host disease (GVHD) intensively stained the nucleolar region of target cells in indirect immunofluorescence microscopy. To identify the target antigens, immunoblotting experiments were performed using isolated nuclei, isolated nucleoli, and purified nuclear and nucleolar proteins as the antigen source. The nucleolar phosphoproteins B23 and C23 were identified as the main target antigens. Eleven of 19 extensive chronic GVHD sera reacted with these nucleolar phosphoproteins. In addition, four sera recognized histone H1, and two sera recognized the nuclear lamins A and C. Our patients reacting with the nucleolar proteins had symptoms resembling that of scleroderma or Sjogren's syndrome. PMID- 1737094 TI - Transplantation of bone marrow cells from transgenic mice expressing the human MDR1 gene results in long-term protection against the myelosuppressive effect of chemotherapy in mice. AB - Many human cancers that are initially responsive to chemotherapy eventually fail to respond to treatment. For some drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow (BM) limit cytotoxic therapy. Approaches to prevent or circumvent BM toxicity are therefore a high priority of research on dose escalation protocols. In this study, we have transplanted BM cells from transgenic mice that constitutively express physiologic amounts of a functional human multidrug resistance (MDR1) cDNA to lethally irradiated C57BL/6 x SJL F1 mice (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and BM specimens as indicated by Southern blot analysis, and expressed MDR1 messenger RNA in BM samples as detected by slot blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal BM were drug sensitive. Finally, the chemoprotection afforded by the MDR1 gene could readily be reversed by adding chemosensitizers such as cyclosporin A and R-verapamil to chemotherapy. Hence, it appears that BM cells expressing the human MDR1 gene maintain this function after transplantation to host animals for a minimum of 10 months, and confer multidrug resistance to these BM recipients. This selective advantage conferred by expression of the MDR1 cDNA suggests a strategy for the use of MDR1 gene therapy in cancer chemotherapy and for the introduction of otherwise nonselectable genes into BM. PMID- 1737095 TI - Basophil and mast cell lineages in vitro and in vivo. PMID- 1737096 TI - Demonstration of a human epsilon-globin gene silencer with studies in transgenic mice. AB - The human epsilon-globin gene displays normal developmental regulation in transgenic mice; it is expressed only in embryonic and in definitive erythroid cells. We show here that deletion of a negative element located between -182 and 467 bp upstream of the epsilon-globin gene cap site results in continuation of epsilon gene expression in the definitive erythroblasts of the fetal liver and in the red blood cells of adult transgenic mice. These data provide direct in vivo evidence that cis acting silencing elements are involved in the developmental control of the epsilon-globin gene. PMID- 1737097 TI - Complications and outcome in childhood acute lymphoblastic leukemia with hyperleukocytosis. AB - Hyperleukocytosis (greater than or equal to 100 x 10(9) leukocytes/L) was identified at diagnosis of acute lymphoblastic leukemia in 64 of 358 patients enrolled on St Jude Total Therapy Study XI from February 1984 to September 1988. These children received a seven-drug induction regimen followed by high-dose methotrexate, cranial irradiation at 1 year of remission, and 120 weeks of continuation therapy with rotational administration of four drug pairs. The 27 patients with leukocyte counts greater than or equal to 200 x 10(9)/L underwent initial cytoreduction via leukapheresis or exchange transfusions. The complete remission rate for patients with hyperleukocytosis (94%) was similar to that for the overall series (96%). Stepwise regression analysis showed that hyperleukocytosis was significantly associated with age less than 1 year at diagnosis, T-cell immunophenotype, leukemic cell ploidy less than or equal to 50 chromosomes, organomegaly, and elevated lactic dehydrogenase. The 27 patients with extreme hyperleukocytosis (greater than 200 x 10(9)/L) different from the other 37 children only in a higher frequency of French-American-British (FAB) L2 morphology. Estimated 4-year event-free survival (EFS) was 52% +/- 8% (SE) for patients with hyperleukocytosis versus 79% +/- 4% for patients with leukemic counts less than 100 x 10(9)/L (P less than .0001). Patients with leukocyte counts of 100 to 200 x 10(9)/L had a significantly better EFS than those with counts greater than 200 x 10(9)/L (64% +/- 10% v 34% +/- 14%; P = .04). Thus, the therapy in this trial proved satisfactory for children with leukocyte counts of 100 to 200 x 10(9)/L; further study is needed to improve the outlook for children with counts greater than 200 x 10(9)/L. PMID- 1737098 TI - Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia. AB - Thirty-four adults with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m2 intravenously over 1 hour daily for 5 days and cytosine arabinoside (ara-C) 3 g/m2 intravenously over 2 hours every 12 hours for six doses, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 125 microgram/m2 intravenously over 4 hours daily until recovery of granulocytes above 2.0 x 10(3)/microL. Their outcome was compared with 29 prognostically similar historical control patients treated with the identical chemotherapy without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (13 of 34 [38%] v 11 of 29 [38%]). There was a trend for less remission induction mortality in the GM-CSF-treated patients (2 of 34 [6%] v 6 of 29 [21%]; P = .08), but, conversely, a higher rate of resistant disease (19 of 34 [56%] v 10 of 29 [34%]; P = .09). Recovery of granulocyte counts above 500/microL was significantly faster in the GM-CSF-treated group (25 days v 33 days; P less than .01), but there was no reduction in the incidence of febrile episodes (91% v 93%) or of documented infections (59% v 59%). Survival was prolonged in the GM-CSF-treated patients but was not of clinical relevance (31 v 20 weeks; P = .05). In summary, the addition of GM-CSF to intensive chemotherapy in refractory adult ALL was associated with a reduction in the remission induction mortality, probably secondary to a shorter duration of granulocytopenia, but not with an improvement in complete response rates. PMID- 1737099 TI - Monoclonal antibodies specific for low-affinity interleukin-3 (IL-3) binding protein AIC2A: evidence that AIC2A is a component of a high-affinity IL-3 receptor. AB - Mouse interleukin-3 (IL-3) binds to its receptor with high and low affinities. Using anti-Aic2 antibody, two distinct cDNAs (AIC2A and AIC2B) were isolated. The AIC2A gene encodes a protein of 120 Kd that binds IL-3 with low affinity, whereas the AIC2B gene encodes a protein that is 91% identical to AIC2A at the amino acid level, but which does not bind IL-3. To study the structure of the functional high-affinity IL-3 receptor (IL-3R), we generated specific monoclonal antibodies against the AIC2A protein. We produced a soluble AIC2A protein by inserting a termination codon at the beginning of the transmembrane domain of the AIC2A cDNA. Soluble AIC2A protein expressed in COS7 cells was purified to homogeneity and three anti-AIC2A monoclonal antibody-producing hybridomas (3D1, 3D4, and 9D3) were obtained from a rat immunized with the purified soluble AIC2A protein. The antibodies were specific for the AIC2A protein and did not bind to the AIC2B protein. Using chimeric receptors between AIC2A and AIC2B, recognition sites of the antibodies were mapped. The antibodies immunoprecipitated a 120-Kd protein from IL-3-dependent PT18 cells. The N-terminal sequence of the 120-Kd protein was consistent with the predicted processing site of the signal sequence of the AIC2A protein. Staining of IL-3-dependent and IL-3-independent cell lines with the 9D3 antibody were consistent with the IL-3 binding. The 9D3 antibody inhibited both the high-affinity IL-3 binding and the low-affinity binding, as well as IL-3 dependent proliferation. These results indicate that the AIC2A protein is a binding component of a high-affinity IL-3R. PMID- 1737100 TI - Heterogeneity in filamentous actin content among individual human blood platelets. AB - The content of filamentous actin in individual platelets was measured by flow cytometry, using a fluorescent probe specific for filamentous actin (F-actin), 7 nitrobenz-2-oxa-1,3-phallacidin (NBD-phallacidin). NBD-phallacidin binding to fixed platelets was specific in that either pretreatment of platelets with unlabeled phallacidin or absorption of NBD-phallacidin by rabbit skeletal F actin, but not globular actin (G-actin), resulted in a significant loss in the bound fluorescent probe. Mean NBD-phallacidin binding to fixed platelets varied with the agonist and paralleled the changes in F-actin reported with the DNAse I inhibition assay. (1) NBD-phallacidin binding increased with stimulation by ADP, U46619 (a prostaglandin H2 analogue), or collagen and paralleled shape change. (2) Epinephrine did not increase NBD-phallacidin binding. (3) Platelets treated at 4 degrees C contained more F-actin than did platelets kept at 37 degrees C. (4) Cytochalasin D (10 mumol/L) inhibited the increase of phallacidin binding to individual platelets stimulated by either ADP or U46619. In measurements of cytosolic free calcium concentration ([Ca2+]i) by flow cytometry in Indo-1-loaded platelets, ADP's dose-response for actin polymerization was similar to that for calcium mobilization. As shown by flow cytometry, a tail population that had a minimal increase in F-actin upon stimulation with ADP or U46619 also contained the platelets with the least forward and right angle light scattering, which are functions of platelet size and shape. When platelets treated with NBD-phallacidin were incubated with S12-murine monoclonal antibody (a marker of alpha-granule secretion detected by phycoerythrin-conjugated antimouse IgG second antibody), phallacidin fluorescence paralleled S12 binding. Thus, human blood platelets are heterogeneous in regard to actin polymerization at rest and in association with platelet activation; different degrees of phallacidin binding may identify functionally different platelet populations. PMID- 1737101 TI - Platelet adhesion to laminin: role of Ca2+ and Mg2+ ions, shear rate, and platelet membrane glycoproteins. AB - The adhesion of platelets to purified laminin under flow conditions was investigated. Adhesion to laminin was strongly dependent on the presence of divalent cations. In the absence of cations platelet adhesion (8% coverage in 5 minutes) was maximal at a shear rate of 100/s and no adhesion could be detected at shear rates above 800/s. In the presence of 0.8 mmol/L Mg2+ and 2 mmol/L Ca2+ platelet adhesion reached its maximum (30% coverage) around 800/s. At 1,800/s platelets still adhered to purified laminin (coverage of 6%). Antibodies against the E8 domain of laminin and antibodies against the alpha 6 and beta 1 chains of platelet membrane glycoprotein very late activation antigen-6 (VLA-6), completely inhibited adhesion. No inhibition was found with antibodies against glycoprotein IIb:IIIa, against the alpha 2 chain of VLA-2, and against the alpha 5 chain of VLA-5. Fibronectin and von Willebrand factor were not involved in laminin dependent adhesion. Anti-VLA-6 partly inhibited platelet adhesion to the extracellular matrix of endothelial cells at shear rates below 800/s. Preincubation of the matrices with antilaminin E8 antibodies did not influence the adhesion. These results show that purified laminin supports platelet adhesion and that the presence of VLA-6 is important for platelet adhesion under flow conditions. The protein in the matrix with which VLA-6 interacts is currently unknown. PMID- 1737102 TI - Localization of platelet osteonectin at the internal face of the alpha-granule membranes in platelets and megakaryocytes. AB - Osteonectin is a 32-Kd phosphoglycoprotein originally described in bone but also found in platelets. Platelet and bone osteonectin are different both structurally and immunologically. We have previously shown that platelet osteonectin, by binding to thrombospondin, is involved in the secretion-dependent phase of the platelet aggregation process. In this study, we used antiosteonectin antibodies in combination with immunogold labeling to investigate by electron microscopy the fine localization of osteonectin within normal and gray platelets. Using both a polyclonal and monoclonal antibody ON3, osteonectin was specifically located at the internal face of alpha-granule membranes within normal platelets. Osteonectin was not distributed within all alpha-granules, probably because of its low platelet content. In addition, using immunofluorescence, osteonectin could also be detected in immature and mature megakaryocytes with a granular pattern of staining, suggesting that osteonectin is synthesized by megakaryocytes. Using platelets from two patients with gray platelet syndrome, osteonectin was absent within all abnormal small alpha-granules, but was detected in some rare normal sized alpha-granules. In separate double-label studies, thrombospondin and von Willebrand factor did not colocalize with osteonectin in resting platelets. However, osteonectin was located at the inner face of the alpha-granules, as it is for alpha-granule membrane protein GMP-140 and glycoprotein IIb-IIIa. These results, taken together with the fact that monoclonal antibodies to osteonectin bind only to the surface of activated platelets, suggest that platelet osteonectin is redistributed to the cell surface during fusion of alpha-granule membranes with the plasma membrane. PMID- 1737103 TI - Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1. AB - To determine the mechanism by which platelet counts increase after corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we studied the platelet kinetics using prednisolone (PDN)-treated ITP-prone mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40 days), but not in nontreated controls (0.60 +/- 0.24 days, P less than .01). No increase in platelet production (platelet turnover) was found in PDN-treated W/B F1 mice, but significant decreases in platelet-associated antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted. Studies on organ localization of radiolabeled platelets showed that hepatic uptake significantly decreased in the treated W/B F1 mice, but not in nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-endothelial phagocytic activity in W/B F1 mice, we studied in vivo clearance of IgG sensitized, 51Cr-labeled autologous erythrocytes. W/B F1 mice treated with PDN showed a marked impairment of their ability to clear these cells, although PDN had little effect on the number of splenic or hepatic macrophage Fc gamma receptors. These results and our previous findings of splenectomy suggest that PDN improves platelet counts not only by suppressing systemic reticulo endothelial phagocytic function but also by reducing antibody production. PMID- 1737104 TI - Adhesive protein expression on thrombin-stimulated platelets: time-dependent modulation of anti-fibrinogen, -fibronectin, and -von Willebrand factor antibody binding. AB - Platelets contain a pool of endogenous adhesive proteins that can be released and may bind to surface membrane receptors under appropriate conditions. Because the binding of exogenous fibrinogen to platelets was shown previously to be accompanied by a time-dependent decrease in fibrinogen accessibility to antibody and enzymes, studies were performed to evaluate changes in the expression of endogenous fibrinogen released from thrombin-stimulated platelets using monospecific polyclonal and monoclonal antibody F(ab')2 fragments. Parallel studies were performed to compare the expression of released fibronectin and von Willebrand factor (vWF). Binding of polyclonal antibody F(ab')2 fragments directed against individual adhesive proteins was inhibited by EDTA or the 10E5 monoclonal antibody, suggesting that fibrinogen, fibronectin, and vWF expression was mediated, in large part, by divalent cation-dependent interactions with the glycoprotein IIb-IIIa complex. Interestingly, when polyclonal antibody F(ab')2 fragments were added to platelet suspensions at discrete times after thrombin stimulation, antifibrinogen F(ab')2 binding decreased by 72% +/- 15% (mean +/- SD, n = 22) over a 60-minute time course, whereas antifibronectin and anti-vWF antibody F(ab')2 fragment binding changed minimally (6% +/- 23%, n = 22 and 3% +/ 26%, n = 14, respectively). Similar observations were made with monoclonal antibodies. Parallel experiments using 125I-labeled fibrinogen as a marker indicated that the observed decrease in antifibrinogen F(ab')2 binding was not accompanied by fibrinogen dissociation. Moreover, antibody accessibility to platelet-bound fibrinogen could be restored after Triton X-100 platelet lysis. The data suggest that fibrinogen, fibronectin, and vWF are not coordinately expressed on thrombin-stimulated platelets. Rather, fibrinogen expression appears transient compared with the expression of fibronectin and vWF. The ability of platelets to secrete and organize adhesive proteins on their surface is likely to have important implications for hemostasis and thrombosis. PMID- 1737105 TI - Spectrum of toxicities of amino acid methyl esters for myeloid cells is determined by distinct metabolic pathways. AB - L-leucine methyl ester (Leu-OMe), Leu-Leu-OMe, Phe-OMe, and Glu-(OMe)2 are toxic to mononuclear phagocytes (M phi) and neutrophils. In the present studies, the mechanism of this toxicity was examined. A concentration of NH4Cl known to neutralize lysosomal pH and to block conversion of Leu-OMe to the dipeptide condensation product Leu-Leu-OMe inhibited Leu-OMe- or Glu-(OMe)2- but not Leu Leu-OMe-mediated M phi toxicity. Leu-OMe-, Glu-(OMe)2-, or Leu-Leu-OMe-mediated killing of M phi was prevented by Gly-Phe-CHN2, a specific inhibitor of the thiol protease, dipeptidyl peptidase I (DPPI). Neither NH4Cl nor Gly-Phe-CHN2 prevented Phe-OMe-mediated M phi toxicity. In contrast, inhibition of M phi serine esterase activity prevented Phe-OMe- but not Leu-OMe- or Glu-(OMe)2-mediated killing of M phi. The myeloid tumor lines U937, HL60, and THP-1 were found to be uniformly enriched in DPPI and susceptible to Leu-Leu-OMe but not Leu-OMe toxicity. Whereas HL60 were resistant to Phe-OMe, THP-1 cells were killed by this agent. Incubation of peripheral blood mononuclear cells with Leu-OMe resulted in loss of natural killer (NK) functions and cytotoxic T lymphocytes (CTL) precursors, a process that requires the DPPI-dependent generation of membranolytic polymerization products. Phe-OMe had no toxic effects on NK cells or CTL precursors. These results indicate that Leu-OMe and Glu-(OMe)2 toxicity for M phi is related to the production of higher molecular weight hydrophobic polymerization products via the sequential action of two nonserine esterase lysosomal enzymes. In contrast, Phe OMe toxicity for myeloid cells was found to correlate with serine esterase mediated intracellular trapping of high concentrations of the free amino acid Phe. These distinct enzymatic mechanisms may provide a unique means of targeting agents capable of selectively deleting cells of myeloid lineage. PMID- 1737106 TI - Mutational activation of the N-ras oncogene assessed in primary clonogenic culture of acute myeloid leukemia (AML): implications for the role of N-ras mutation in AML pathogenesis. AB - The number of steps involved in the pathogenesis of acute myeloid leukemia (AML) is unclear. The initiating event would be expected to exist in all leukemic cells, but subsequent events may be subclonal. If several genetic events occur, they may cooperate within the same cell or be alternatively acquired by different subclones. These possibilities cannot be adequately analyzed in DNA prepared directly from patient specimens. In this study, N-ras mutations demonstrable in DNA prepared from peripheral blood of 10 patients with AML were examined in primary in vitro colonies (AML-colony-forming units [CFU]) grown from these patients. Both colonies containing the mutant gene and colonies containing normal allele only were obtained from each patient. The proportion of colonies containing no mutant allele varied among patients (5% to 57%). A subset of mutation containing colonies appeared to have lost the normal allele in nine of 10 AML cases analyzed. In the four cases with two N-ras mutations, the two mutations were found to exist in different subclones. In these cases, macroscopic colonies (AML-MCFU) were also obtained using an assay system designed to select for earlier clonogenic cells than in the AML-CFU assay. The N12cys mutation in AML10 was found in the CFU, but not in the MCFU, and the N12asp mutation in AML43 was found in the MCFU, but not in the CFU. These results suggest that N-ras mutation is a postinitiation event in AML that contributes to the outgrowth of more malignant subclones. Where two mutations are found in a case of AML, they appear to have been acquired by separate subclones, which may show different degrees of differentiation. PMID- 1737107 TI - Antiproliferative effects of interleukin-4 on freshly isolated non-Hodgkin malignant B-lymphoma cells. AB - The pattern of in vitro growth response of freshly isolated non-Hodgkin malignant lymphoma B cells (NHML) to cytokines was investigated. Ten tumor specimens of low or intermediate-grade malignancy were selected for study. To assess their proliferative capacity in vitro, B-lymphoma cells were activated through ligation of their surface Ig receptor with insolubilized anti-IgM antibodies or Staphylococcus aureus strain Cowan I (SAC). In the great majority of cases, interleukin-2 (IL-2) was the sole factor that significantly and reproducibly stimulated DNA synthesis in NHML activated through their surface Igs. Other B cell tropic factors, including IL-4, IL-5, IL-6, and tumor necrosis factor-alpha (TNF-alpha), failed to elicit a growth response in most of the IL-2-responsive neoplastic samples. However, one specimen among 10 exhibited the opposite pattern of response and proliferated following culture with IL-4 and anti-Ig reagents, but not after IL-2 stimulation. Three specimens could also be induced for DNA synthesis on cross-linking of their surface Igs in the absence of exogenous growth factors. Although IL-4 could not support the in vitro growth of the majority of NHML cases, it strongly suppressed the proliferative signals delivered to these cells by anti-Ig reagents used alone or in combination with IL 2. Our data suggest that, in most cases, IL-4 essentially provides growth inhibitory signals to NHML when they are activated through their surface Ig receptors and as such may be considered to be a valid candidate for future therapy of this type of mature B-cell malignancy. PMID- 1737108 TI - Russian report: doctors and health service reform. PMID- 1737109 TI - Who speaks for whom? PMID- 1737110 TI - ABC of vascular diseases. Deep venous insufficiency and occlusion. PMID- 1737111 TI - Noise: breaking the silence. PMID- 1737112 TI - Dogs that bite. PMID- 1737113 TI - Dogs that bite. PMID- 1737114 TI - Apnea monitors and accidental strangulation. PMID- 1737115 TI - Dogs that bite. PMID- 1737116 TI - Febrile convulsions. PMID- 1737117 TI - Restraint of children in cars. PMID- 1737118 TI - Dangers of ozone depletion. PMID- 1737119 TI - Heart valve records falsified. PMID- 1737120 TI - Infection acquired from transplant donor. PMID- 1737121 TI - Risk factors in Alzheimer's disease. PMID- 1737122 TI - Intravenous magnesium in suspected acute myocardial infarction. PMID- 1737123 TI - Urinary incontinence. PMID- 1737124 TI - The health of the nation. PMID- 1737125 TI - Endometrial resection or abdominal hysterectomy in menorrhagia? PMID- 1737126 TI - "Do not resuscitate" orders. PMID- 1737127 TI - "Do not resuscitate orders. PMID- 1737128 TI - Understanding Marfan's syndrome. PMID- 1737129 TI - GP trainees' views on hospital obstetric vocational training. PMID- 1737130 TI - Rugby injuries. PMID- 1737131 TI - The health strategy. PMID- 1737132 TI - AIDS campaigns: putting the message across. PMID- 1737133 TI - Doctors convicted of manslaughter. PMID- 1737134 TI - Wasted drugs in HIV infection and AIDS. PMID- 1737135 TI - Clinical trials in community pharmacies. PMID- 1737136 TI - Psychiatric symptoms and low blood pressure. PMID- 1737137 TI - Guillain-Barre syndrome revisited. PMID- 1737138 TI - Preventing infection in laboratories. PMID- 1737139 TI - Using tympanometry to detect glue ear in general practice. PMID- 1737140 TI - Bone banks. PMID- 1737141 TI - AIDS and hepatitis B in the former Soviet Union. PMID- 1737142 TI - Low blood pressure, low mood? AB - OBJECTIVE: To determine whether a set of physical symptoms is associated with low blood pressure and to investigate the possible role of psychological factors in their occurrence. DESIGN: Analysis of data collected by questionnaire and physical screening from the first phase of the Whitehall II study, a cohort study of an employed population. SETTING: 23 civil service departments in London. SUBJECTS: 10,314 male and female London based civil servants aged between 35 and 55. MAIN OUTCOME MEASURES: Symptoms of dizziness-giddiness and unexplained tiredness; psychological functioning as measured by the 30 item general health questionnaire in which the response "no more than usual" to an item about disease was scored as indicating chronic illness. RESULTS: Dizziness-giddiness in men and unexplained tiredness in both men and women were significantly related to low systolic blood pressure. There was a highly significant inverse relation between general health questionnaire score and systolic blood pressure for both men and women, which persisted after controlling for potentially confounding variables, including age, body mass index, drug treatment, physical illness, and exercise. This association of low blood pressure with physical symptoms was no longer significant when general health questionnaire score was controlled for. CONCLUSIONS: There seems a strong relation between low systolic blood pressure and minor psychological dysfunction. Associated physical symptoms seem to be secondary to the primary disturbance in mental state. PMID- 1737143 TI - What happens to homeless mentally ill people? Follow up of residents of Oxford hostels for the homeless. AB - OBJECTIVES: To follow up severely mentally ill residents of hostels for the homeless to determine their social and psychiatric outcome. DESIGN: Follow up at 18 months of hostel residents previously assessed with psychiatric and behavioural measures. SETTING: Two Oxford hostels for the homeless. SUBJECTS: 48 hostel residents previously identified as disabled by mental illness. MAIN OUTCOME MEASURES: Current housing, admissions to psychiatric hospital, violent or antisocial behaviour, and score on standardised behavioural rating. RESULTS: 45 of the 48 residents were traced. 27 had remained in the hostels; only 10 had been rehoused, mainly in bedsits or with their families. 16 had a poor outcome as judged by death (four subjects), lengthy hospital readmission (two), marked deterioration in behaviour (six), sleeping rough (one), or disappearance (three). CONCLUSION: More effort is needed to provide suitable housing for homeless mentally ill people. PMID- 1737144 TI - Alcohol consumption and its relation to cardiovascular risk factors in British women. AB - OBJECTIVE: To examine the relation between alcohol consumption and risk factors for coronary heart disease in women. DESIGN: Cross sectional study of a stratified random sample of the population grouped into five categories of habitual alcohol consumption. SETTING: People registered with general practitioners at two large health centres in east Bristol, England. SUBJECTS: 1048 women aged 25-69 years. MAIN OUTCOME MEASURES: Fasting plasma concentrations of insulin, total cholesterol, total triglycerides, and high density lipoprotein cholesterol, including its subfractions HDL2 and HDL3, and body mass index. RESULTS: Compared with non-drinkers women consuming a moderate amount of alcohol (1-20 g/day) had lower plasma concentrations of triglycerides, by 0.19 mmol/l (95% confidence interval 0.07 to 0.35); cholesterol, by 0.4 mmol/l (0.19 to 0.61); and insulin, by 1.4 mU/l (0.43 to 1.97) and a lower body mass index, by 1.2 kg/m2 (0.43 to 1.97). They also had higher concentrations of high density lipoprotein cholesterol, by 0.09 mmol/l (0.03 to 0.15); HDL2 cholesterol by 0.05 mmol/l (-0.02 to 0.10) and HDL3 cholesterol, by 0.06 mmol/l (0.06 to 0.11). All these were independent of body mass index, smoking habits, and taking oral contraceptives. CONCLUSIONS: Moderate alcohol consumption is associated with lower levels of cardiovascular risk factors in women. Insulin may have a central role. PMID- 1737145 TI - Effect of "fast track" admission for acute myocardial infarction on delay to thrombolysis. AB - OBJECTIVE: To evaluate the impact of a fast track triage system for patients with acute myocardial infarction. DESIGN: Comparison of delays in admission to hospital and in receiving thrombolytic treatment before and after introducing fast track system with delays recorded in 1987-8. Patients fulfilling clinical and electrocardiographic criteria for myocardial infarction were selected for rapid access to the cardiac care team, bypassing evaluation by the medical registrar. SETTING: Major accident and emergency, cardiac and trauma centre. SUBJECTS: 359 patients admitted to the cardiac care unit during 1 February to 31 July 1990 with suspected acute infarction. MAIN OUTCOME MEASURES: Accuracy of diagnosis and delay from arrival at hospital to thrombolytic treatment. RESULTS: 248 of the 359 patients had myocardial infarction confirmed, of whom 127 received thrombolytic treatment. The fast track system correctly identified 79 out of 127 (62%) patients who subsequently required thrombolytic treatment. 95% (79/83) of patients treated with thrombolysis after fast track admission had the diagnosis confirmed by electrocardiography and enzyme analysis. The median delay from hospital admission to thrombolytic treatment fell from 93 minutes in 1987-8 to 49 minutes in fast track patients (p less than 0.001). Delay in admission to the cardiac care unit was reduced by 47% for fast tract patients (median 60 minutes in 1987-8 v 32 minutes in 1990, p less than 0.001) and by 25% for all patients (60 minutes v 45 minutes, p less than 0.001). CONCLUSION: This fast track system requires no additional staff or equipment, and it halves inhospital delay to thrombolytic treatment without affecting the accuracy of diagnosis among patients requiring thrombolysis. PMID- 1737146 TI - Irritable bowel syndrome in the general population. AB - OBJECTIVE: To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population. DESIGN: Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome. SETTING: Urban population in Southampton and mixed urban-rural population in Andover, Hampshire. RESULTS: A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity. CONCLUSION: Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction. PMID- 1737147 TI - Prevalence of HIV infection among ex-prisoners in England. PMID- 1737148 TI - A clinical trial of minocycline in lepromatous leprosy. PMID- 1737149 TI - Suffocation from misuse of gas masks during the Gulf war. PMID- 1737150 TI - Using clinicopathological analysis of general practitioner skin surgery to determine educational requirements and guidelines. AB - OBJECTIVE: To study the impact of skin surgery in general practice on the workload of a pathology laboratory and to identify what further training might be helpful. DESIGN: Analysis of skin biopsy specimens from general practitioners before and after their new contract to determine numbers of specimens, changes in diagnoses, adequacy of treatment of malignant tumours, and areas of low diagnostic accuracy. SETTING: District general hospital. SUBJECTS: All 1017 skin biopsy specimens from general practice for 15 months before and 12 months after the new general practitioner contract. RESULTS: The number of pathology specimens received increased from 16 to 65 per month (median = 6 submitted by each general practitioner in the post-contract year). The proportion of the more common pathological diagnoses was unchanged between the two periods, but the proportion of correctly diagnosed naevi, cysts, and seborrhoeic keratoses increased in the second. Although few diagnoses were overtly incorrect, accurate diagnosis of dermatofibromas and malignancies decreased after the contract, and the overall correct diagnosis rate for seborrhoeic keratoses, dermatofibromas, rashes, and malignancies was below 30%. Only nine out of 21 squamous cell carcinomas were adequately excised with tumour free margins, and follow up of malignant tumours may have been inadequate. CONCLUSIONS: Skin surgery in general practice has advantages but matters of concern are the increase in laboratory workload, the excision of some benign lesions, and the inappropriateness of biopsy of rashes. Squamous cell carcinoma and other malignant tumours submitted for pathological examination were often unsuspected and inadequately excised, and heightened suspicion is recommended. Pathology request forms may need redesigning to encourage provision of clinical details. PMID- 1737151 TI - Diagnostic value of microtympanometry in primary care. AB - OBJECTIVE: To determine the reliability, validity, and feasibility of a new hand held microtympanometer. DESIGN: Comparison of microtympanometry by two independent observations of a general practitioner and a nurse, and against a validated reference instrument. SETTING: Primary care health centre of a school for the deaf in the United States. SUBJECTS: 111 schoolchildren receiving a regular check up. MAIN OUTCOME MEASURES: Tympanometry with the Grason Stadler 28, classified with a slightly modified Jerger's classification. RESULTS: Interobserver reliability was 0.95 (Cohen's kappa). Results of microtympanometry were highly comparable with results of the reference instrument (likelihood ratio of positive results, 161.2). CONCLUSIONS: The microtympanometer could be used in general practice: it is hand held, child friendly, easy to handle, and accurate. PMID- 1737152 TI - Policy on cigarette advertising and coverage of smoking and health in European women's magazines. PMID- 1737153 TI - Who's for growth hormone? PMID- 1737154 TI - FHSA medical advisers: friends or foes? PMID- 1737155 TI - Prison medicine: beginning again. PMID- 1737156 TI - Drug treatment for acute upper gastrointestinal bleeding. PMID- 1737157 TI - Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. AB - OBJECTIVE: To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN: Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING: The medical wards of University and City Hospitals, Nottingham. SUBJECTS: 1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES: Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS: Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS: Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena. PMID- 1737158 TI - Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life. AB - OBJECTIVE: To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN: Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING: Hertfordshire and Preston, England. SUBJECTS: 591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES: Plasma fibrinogen and factor VII concentrations. RESULTS: Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS: Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period. PMID- 1737159 TI - Diabetes in prison: can good diabetic care be achieved? AB - OBJECTIVE: To investigate the clinical characteristics and metabolic control of diabetic patients given structured diabetic care in prison. DESIGN: Survey of diabetic men serving prison sentences during a 22 month period in a large British prison. SETTING: HM Prison, Walton, Liverpool. SUBJECTS: 42 male diabetic prisoners, of whom 23 had insulin dependent and 19 non-insulin dependent diabetes. MAIN OUTCOME MEASURES: Episodes of diabetic instability, glycated haemoglobin concentrations, body mass index. RESULTS: No serious diabetic instability occurred. Between the initial assessment by the visiting consultant diabetologist and a second assessment 10 weeks later glycated haemoglobin concentrations had fallen from 10.8 (SD 2.9)% to 9.8 (2.4)% (p less than 0.05) in prisoners with insulin dependent diabetes and from 8.7 (1.9)% to 7.6 (1.2)% (p less than 0.05) in those with non-insulin dependent diabetes. Good glycaemic control continued, a mean glycated haemoglobin concentration of 7.6 (1.5)% being recorded in seven men remaining in prison for six to 18 months. Mean body mass index (weight (kg)/(height(m))2) did not change during the study (insulin dependent prisoners 23.3 (SD 2.1), non-insulin dependent prisoners 27.9 (3.8)). CONCLUSIONS: Good diabetic metabolic control is usual in prison, probably due to the rigid dietary regimen, no alcohol, and compliance with treatment. Many younger men had defaulted from their home diabetic clinics, and imprisonment allowed screening for diabetic complications and reassessment of treatment. Structured diabetic care should be offered in all prisons. PMID- 1737160 TI - Diurnal variation in incidence of stroke: Oxfordshire community stroke project. AB - OBJECTIVE: To determine whether diurnal variation occurs in the onset of stroke. DESIGN: Community based study over four years. SETTING: Oxfordshire, United Kingdom. SUBJECTS: 105,000 people, of whom 675 had a first ever stroke. 545 had a cerebral infarction, 66 had primary intracerebral haemorrhage, 33 had subarachnoid haemorrhage, and in 31 the type of stroke was not known. MAIN OUTCOME MEASURES: Time of stroke and degree of activity at onset. RESULTS: In the 578 patients for whom it was known whether onset occurred while asleep or awake, the proportion with onset during sleep was 25% (135/545) for cerebral infarction, 17% (11/66) for primary intracerebral haemorrhage, and 0% (0/33) for subarachnoid haemorrhage. This difference persisted if patients in whom it was not known whether they were asleep or awake at onset were classed as asleep. For all stroke types together there was a significant (chi 2 = 218.7, p less than 0.001) diurnal variation with a morning peak between 0800 and 1000, which persisted even after allowing for strokes first noted on waking by redistributing the hour of onset through the preceding eight hours (chi 2 = 47, p less than 0.001). A significant diurnal variation was also found in the onset of cerebral infarction (peak 0800 1000, chi 2 = 208.4, p less than 0.001). Fewer patients had other forms of stroke and the diurnal variations for primary intracerebral haemorrhage (peak 1000-1200) and subarachnoid haemorrhage (peaks 0800-1000 and 1800-2000) were not significant. There seemed to be a second smaller peak for all types of stroke. CONCLUSIONS: All types of stroke are most likely to occur after waking in the morning. The cause of the circadian variation requires further study. PMID- 1737161 TI - Octreotide and Graves' ophthalmopathy and pretibial myxoedema. PMID- 1737162 TI - Quality of data in the Manchester orthopaedic database. AB - OBJECTIVE: To determine the completeness and accuracy of data in a computerised clinical information system (Manchester orthopaedic database) in comparison with the data available through the Hospital Activity Analysis. DESIGN: Retrospective review of case notes, computer data, and Hospital Activity Analysis data. SETTING: Orthopaedic unit in a district general hospital in Manchester. SUBJECTS: 200 random patient records distributed through the period of use of the computer system (1 October 1988 to 31 March 1990) and 121 records for random admissions between 1 April 1989 and 31 March 1990, 71 of which were included in the previous sample. MAIN OUTCOME MEASURES: Conformity of the computer record key words and Hospital Activity Analysis codes to an ideal key word record and ideal code record drawn up by one investigator from the clinical notes; overall quality (completeness times accuracy). RESULTS: Overall completeness of the data in the orthopaedic database was 62% and the accuracy was 96%. Completeness improved after feedback to doctors on the use of key words in regular audit meetings. Completeness was higher in inpatient than outpatient records (69.9% v 53.7%, p less than 0.001) and when a new key word was required compared with missing and incorrect key words (both p less than 0.001). Completeness was lower when the key word was required of a senior registrar (p less than 0.05). Accuracy was not significantly different. The completeness of Hospital Activity Analysis data was 90.5% and accuracy 69.5%. Thus the overall data quality was similar in both systems. CONCLUSIONS: Even in a system designed for simple and efficient data capture, compliance by users was poor. Accuracy was high, suggesting that users understood the principles of data entry. Completeness of data capture can be improved by providing feedback to users on use of the system and performance. Improvements in future versions of the software should improve performance. PMID- 1737163 TI - Quality assurance in Finland. PMID- 1737164 TI - ABC of vascular diseases. Acute ischaemia of the leg. PMID- 1737165 TI - Hazards of pharmacological tests of growth hormone secretion in childhood. PMID- 1737166 TI - Drinking water--doubts about quality. PMID- 1737167 TI - Europe and nutrition: prospects for public health. PMID- 1737168 TI - Rationing. PMID- 1737169 TI - Economic approach to priority setting. PMID- 1737170 TI - Cost effectiveness of magnetic resonance imaging. PMID- 1737171 TI - Cost effectiveness of magnetic resonance imaging. PMID- 1737173 TI - Chorionic villus sampling. PMID- 1737172 TI - Glasgow coma scale and gag reflex. PMID- 1737174 TI - Chaos theory. PMID- 1737175 TI - Could an outbreak of poliomyelitis occur in the UK? PMID- 1737176 TI - Resuscitation and hypothermia. PMID- 1737177 TI - Caring for larger lists. PMID- 1737178 TI - Training in obstetrics. PMID- 1737179 TI - Bioeconomics and behavioural ecology. Special issue in honor of Colin W. Clark. PMID- 1737180 TI - Design of a clinical engineering management information system. PMID- 1737181 TI - Collaboration between nurse researchers and biomedical engineers. PMID- 1737182 TI - Development of a digital signal acquisition system for epilepsy surgery. PMID- 1737183 TI - A comprehensive cardiovascular waveform analysis program for IBM-compatible personal computers. AB - Computerized cardiovascular waveform processing has become a necessary and fundamental tool in the analysis of physiologic data. The availability of numerous commercial data-analysis programs has significantly enhanced the efficiency of waveform analysis. Many such programs come with their own programming language, which enables the researcher to create an application program suited to a specific series of calculations. Once written, an application program can significantly increase the efficiency with which data from a specific experiment can be analyzed. However, creating or modifying a program for each new experimental protocol can be time-consuming, especially in the error-detection and verification stages. Single-purpose programs also prove somewhat inflexible to unexpected changes in experimental formats. These problems suggested the need for a more flexible program, but one that is nevertheless specifically suited to the analysis of cardiovascular signals. This need led to the development of a program designed in collaboration with surgeons and physiologists. This program addresses some important analysis problems in cardiovascular research, and allows the user to survey and manipulate cardiovascular waveforms in an intuitive and spontaneous manner. PMID- 1737184 TI - Comparative study of a 15-MHz focused ultrasonic transducer and a 15-MHz unfocused ultrasonic transducer for clinical in-vivo skin-thickness measurements in human subjects. AB - A commercial focused 15-MHz immersion ultrasonic transducer and a commercial unfocused 15-MHz thickness-gaging ultrasonic transducer were evaluated for invivo skin-thickness measurements in humans. The unfocused transducer produced thicker skin measurements than did the focused transducer but both measurements were generally within previously reported ranges. The differences in the determined thicknesses may have been a result of the uneven nature of the dermissubcutaneous tissue interface and the ability of the focused transducer to better follow this interface. PMID- 1737185 TI - Evaluation of finger blood pressure monitoring instruments. AB - Self-blood pressure monitoring can be critical in the management of hypertension, but it is often awkward and cumbersome. One attempt to improve the ease with which such measurements are made was the development of electronic, digital, automatic monitors for measurement of blood pressure in the finger. The purpose of this study was to evaluate the accuracy, reliability, failure rate, and ease of operation of these devices. While these finger devices were found easier to use than the traditional brachial-artery methods, their accuracies and reliabilities were lower. The greater responsiveness of the digital arteries to changes in local conditions is suggested as the cause of the lesser accuracy and reliability. The author concludes that blood pressure in the digital arteries of the finger is not sufficiently representative of general systemic blood pressure for clinical purposes. PMID- 1737186 TI - Artificial respiration in the anesthetized horse using bilateral, percutaneous, cervical phrenic-nerve stimulation with needle electrodes: a preliminary report. AB - In this preliminary study, artificial respiration was produced in four anesthetized horses using trains of stimuli applied to long needle electrodes inserted bilaterally at the base of the neck. The needles were insulated to within 1 cm of the tips. The frequency of the stimuli (0.1 msec) was 35/sec and the train duration (duration of inspiration) was 1 sec. Inspired volume increased with increasing stimulus intensity. In two animals, inspired volumes of 6 liters were achieved. In another animal 4.5 liters was achieved and in another, 2.5 liters. This lower value probably represented less-than-optimal electrode placement. Artificial percutaneous electrophrenic respiration was maintained for half an hour in every animal using a minute volume equivalent to that when breathing spontaneously. PMID- 1737187 TI - Modern management of heart failure. AB - All grades of symptomatic heart failure have a high mortality rate due to progressive heart failure and sudden death. The aims of management are to establish the correct diagnosis and to select treatment to improve both symptomatology and prognosis. PMID- 1737188 TI - Prenatal and postnatal damage to the male reproductive organs. AB - Various prenatal and postnatal conditions exert a harmful influence on the normal development of the male reproductive organs, and in severe cases lead to sterility in adult life. Early diagnosis is of special importance as effective treatment may be possible in many cases. PMID- 1737189 TI - Reorganizing medical education. AB - The education of doctors has not kept up with changes in medicine, medical technology and the organization of health services. Training at undergraduate and postgraduate level can be rigid and is at times inappropriate. Continuing medical education needs expansion. A review of the work and lifestyle of junior hospital doctors is needed. PMID- 1737190 TI - Osteochondroma in a British neolithic skeleton. AB - The skeletal remains of past populations provide an important source of information on the natural history of disease. Relatively few cases of bone tumours have been reported in archaeological material. This paper describes one of the oldest occurrences of osteochondroma to have been identified in a human skeleton. PMID- 1737191 TI - The coiled spring. AB - Radiological terminology includes a number of interesting and often amusing terms intended to help us understand and remember the pathological abnormality being described. What radiological sign is illustrated in Fig. 1 and what condition does it represent? PMID- 1737192 TI - Tonsils, obesity and obstructive sleep apnoea. AB - In this article the normal effects of anaesthesia on breathing are defined. Specific threats to the airway are identified and illustrated by reference to common clinical conditions. PMID- 1737193 TI - Medicine through the looking glass. PMID- 1737194 TI - Ocular complications of leprosy. PMID- 1737195 TI - Understanding NHS pensions. AB - How much pension will you receive from the NHS Superannulation Scheme upon retirement? Some hospital doctors do not have a clear idea of the likely benefits or indeed any appreciation of the ancillary features included in the NHSSS. It is therefore appropriate to begin this series of articles on pension options for doctors with an overview of the NHS Scheme. PMID- 1737196 TI - Airsick patients. PMID- 1737198 TI - Insulin resistance and blood pressure. PMID- 1737197 TI - Inappropriate surgery for testicular cancer. PMID- 1737199 TI - Free thin osteo-onychocutaneous flaps from the big toe for reconstruction of the distal phalanx of the fingers. AB - Free osteo-onychocutaneous flaps from the big toe have frequently been used for the reconstruction of distal phalangeal loss of the fingers. The thickness of the fatty tissue, however, makes these flaps bulky. We believe this disadvantage can be overcome with a free thin osteo-onychocutaneous flap from the big toe and consider this thin composite flap to be a superior method of reconstruction for the treatment of distal phalangeal loss. PMID- 1737200 TI - Conservative treatment of deep partial thickness hand burns--a long term audit of outcome. AB - Fourteen patients with 23 burned hands assessed as deep partial thickness were studied. Fourteen (61%) hands re-epithelialised within 3 weeks. A detailed hand assessment at a mean of 19 months post-injury was carried out. The functional outcome compared favourably with a group of matched normal controls. There was no statistically significant functional difference between the 7 late grafted hands and the 16 spontaneously healed hands except for total passive motion. Seventeen (74%) hands were considered by the patients to be functionally as good as before the injury. PMID- 1737201 TI - Role of perivenous areolar tissue in the viability of venous flaps: an experimental study on the inferior epigastric venous flap of the rat. AB - This study was performed to investigate how the perivenous areolar tissue affects survival of the rat inferior epigastric venous flap model designed by Yuen and Leung (1991). Five groups of flaps were studied; group A--flap based on an inferior epigastric vein and areolar tissue; group B--flap with a skeletonised vein; group C--control, nonvascularised flap; group D--flap based on perivascular areolar tissue alone; group E--flap with a skeletonised artery and vein. Each group included 40 flaps; 20 of them had a silicone sheet placed under the flap, the other 20 did not. All flaps of group E survived. The success rate of group A with and without a silicone sheet was 60% and 90% respectively. All flaps of the other groups (B, C, D) necrosed. Histological examination of the pedicle showed that many minute vascular channels (single-cell-layered capillaries) were present apart from the inferior epigastric vein. This result confirms the importance of the perivenous areolar tissue in perfusion of the skin island, at least, in the inferior epigastric venous flap in the rat. PMID- 1737202 TI - A new experimental model: the vascular pedicle cutaneous flap over the dorsal aspect (flank and hip) of the rat. AB - Cutaneous vascular anatomy of the flank and the hip was studied in the rat. Investigation was done by anatomical dissection, ink injection to the axial artery and flap harvesting in living rats. Anatomical dissection and India ink injection revealed that the rat's flank and hip skin derives its blood supply from the iliac branch of the iliolumbar artery, which originates from the lateral aspect of the abdominal aorta. The vascular territory of the iliac branch of the iliolumbar artery was defined as follows: the medial border--along the midline of the back from the 12th rib to the proximal part of the tail; the lateral border anterior axillary line corresponding with the length of the medial border; the cephalic border--a line joining the medial and lateral border at the level of the 12th rib; and the caudal border--the posterior lateral line of the hip. On the basis of the vascular territory demarcated by India ink injection, bilateral vascular pedicle island cutaneous flaps were harvested in living rats. Results showed total survival of all flaps. This flap is easily made, and it could be used as a reliable model for flap research. PMID- 1737204 TI - The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma. AB - A historical series of patients with primary cutaneous malignant melanoma is reviewed. These patients had been treated with a single therapeutic dose of irradiation to the tumour and surrounding skin immediately before surgical excision. Some patients had also received a single necrotising dose of radiotherapy to the tumour itself. Recurrence and survival rates have been examined retrospectively in the light of reviewed histology, and compared with other published series. Preoperative radiotherapy was found to have no significant influence on the outcome of surgical treatment of primary malignant melanoma. PMID- 1737203 TI - The effects of soft tissue coverage on bone graft resorption in the craniofacial region. AB - Experiments were performed to study the amount of resorption of endochondral bone grafts in pockets covered by muscle tissue compared to pockets covered by subcutaneous tissue in immature rabbits at 16 weeks post-grafting. In the first group the grafts were used as onlays on the buccal surfaces of the mandible with cover by masseter on one side of the face and subcutaneous tissues on the other. The second experiment was similar but the grafts were fixed semi-rigidly with wiring. In the third the grafts were used as onlays on the cranium with muscle or subcutaneous tissue coverage. The fourth group of bone grafts were implanted into muscle and subcutaneous tissue pockets in the abdominal wall. Bone graft resorption was significantly greater when covered by muscle than by subcutaneous tissue. This effect is probably mediated by movement imparted to the graft by adjacent active muscle, and over-rides any benefits of increased vascularising potential muscle may have. Semi-rigid fixation offered no protection against this effect. PMID- 1737205 TI - The Krakatau syndrome; a late complication of retroglandular mammary augmentation. AB - A late complication of retroglandular mammary augmentation is described, in which severe fibrous capsular contraction with calcification of the capsule causes pressure atrophy of the centre of the mammary gland and sometimes even atrophy of the underlying pectoralis major muscle. The complication was observed in six patients. Two representative cases are described and the treatment is discussed. PMID- 1737206 TI - Delayed debulking of free muscle flaps for aesthetic contouring debulking of free muscle flaps. AB - Although denervated muscle and myocutaneous free flaps atrophy over a period of time, when used for surface coverage they may remain bulky, resulting in a less than optimal aesthetic result. With the availability of a number of donor sites, soft tissue defects can often be reconstructed with like tissue in a single stage. Even though the goal of all plastic surgeons is to achieve a good cosmetic result, special circumstances might dictate that need take precedence over form. We have had six cases where a bulky muscle was used to achieve well vascularised coverage. After wound closure had been successfully accomplished, a secondary debulking procedure was performed safely for a final acceptable aesthetic result. PMID- 1737207 TI - The horn flap: a curved V-Y advancement flap with lateral pedicle. AB - The Horn Flap, a curved V-Y advancement flap with a radially based subcutaneous pedicle, has proven to be a versatile, reliable method of reconstruction following excision of small facial lesions, particularly in the medial canthal area. Entry of the pedicle on the radial, or concave, side makes significant advancement possible. PMID- 1737208 TI - A method of repairing the no. 3 facial cleft. AB - A method of correction of an incomplete no. 3 facial cleft in an infant is presented. It is compared with previously described repairs, and its advantages are outlined. PMID- 1737209 TI - External rhinoplasties: indications for use. AB - The technique, indications and role of external rhinoplasty in nasal surgery are presented. The technique has been utilised in 563 patients with a minimum follow up of 18 months. The external approach has been especially helpful in the severely twisted nose, secondary rhinoplasty, augmentation rhinoplasty, congenital deformities of the nose, closure of septal perforations and in the teaching and learning of rhinoplasty. In this series there were no reported complications attributable to the external approach. PMID- 1737210 TI - Lower eyelid reconstruction by multiple subcutaneous pedicle flaps: a new method. AB - In this paper we present an original technique for the reconstruction of the full thickness of the lower eyelid after excision of neoplasms. The method is based on the mobilisation of multiple pedicle subcutaneous flaps outlined in the same eyelid and supported by a chondro-mucosal graft. This technique is used for central and off-central losses which involve the outer rim or up to 75% of the width of the whole eyelid. This method is an alternative to the Hughes (1945), Mustarde (1981), Tenzel and Stewart (1978) and McGregor (1973) techniques which we have previously used for this type of reconstruction. The follow-up is satisfactory in terms of the oncological, functional and aesthetic aspects, which represent an inseparable triad in reconstructive eyelid surgery. PMID- 1737211 TI - Transtibial transposition of gastrocnemius muscle and musculocutaneous flaps. AB - The medial and lateral gastrocnemius muscle flaps have become the workhorses of proximal calf reconstruction since their initial description by McCraw et al. in 1977. Since that time many authors have presented varying and often ingenious techniques by which the range of these flaps can be expanded. This report adds another modification of the standard gastrocnemius muscle flap: transtibial transposition of the muscle through the posterior cortex. PMID- 1737212 TI - Free medial gastrocnemius myocutaneous flap transfer with neurovascular anastomosis to treat Volkmann's contracture of the forearm. AB - Some articles have reported the use of medial gastrocnemius transfer to repair soft-tissue defects caused by trauma and inflammation (Morris, 1978; Feldman et al., 1978; Arnold and Mixter, 1983). However, we have not found any report describing the use of free medial gastrocnemius myocutaneous flap transfer with neurovascular anastomosis to treat Volkmann's contracture of the forearm. Since 1982, 20 cases of Volkmann's contracture of the forearm have been treated by transfer of medial gastrocnemius flap with neurovascular anastomosis. These 20 patients ranged in age from 6-18 years, with a mean of 10 years. There were 18 males and 2 females. All cases resulted from ischaemia of the extrinsic and intrinsic muscles of the forearm and hand. The most common causes were severe supracondylar fractures or, less frequently, fracture-dislocations of the elbow. Six to twenty months after operation, the transplanted muscles exhibited normal electromyographic potentials, good volume and contractile power with satisfactory functional recovery of the forearms. The deformities of the hand and wrist were also corrected. In this paper we describe the anatomy of the donor site and the operative procedure. PMID- 1737213 TI - Cross leg posterior tibial artery fasciocutaneous island flap for reconstruction of lower leg defects. AB - We have utilised a posterior tibial artery flap from the opposite healthy limb for reconstruction of defects of middle and lower third of leg in 6 patients. The flap can be based either distally or proximally as the need be. The results have been quite encouraging. PMID- 1737214 TI - The exposed total knee replacement prosthesis: a new classification and treatment algorithm. AB - The increased frequency of total knee replacement arthroplasty (TKRA) has been reflected in the number of patients with exposed prostheses referred to this unit. An algorithm has been developed to assist in the preoperative assessment of the wound and this has been tested on 25 patients with wound breakdown following TKRA. The grade of exposure so derived predicts the most appropriate surgical management. The algorithm, grading system and proposed management are described. PMID- 1737215 TI - Squamous cell carcinoma in a tube pedicle forty years after jaw reconstruction. AB - Forty years following extensive jaw resection for adenocarcinoma in a young man, and innovative mandibular reconstruction, a squamous cell carcinoma developed in the tubed pedicle flap used to provide lining for the floor of the mouth. The case is described and a brief history of the early methods of mandibular reconstruction is presented. PMID- 1737216 TI - Reduced thrombogenicity. PMID- 1737217 TI - Xeroderma pigmentosum. PMID- 1737218 TI - The dartos myocutaneous flap--reply. PMID- 1737219 TI - Anterolateral thigh flap: technical tip to facilitate elevation. PMID- 1737220 TI - Neonatal cleft lip repair. PMID- 1737221 TI - Acute effects of cigarette smoking on microcirculation of the thumb. AB - The acute effect of smoking on the microcirculation of the skin of the thumb was investigated in healthy volunteers. Twenty-two were smokers and 10 were non smokers. The flow was assessed by means of laser Doppler flowmetry. The smokers inhaled 2 cigarettes. During smoking of their first and second cigarette respectively, a mean decrease in laser Doppler flow of 23.8% and 29.0% was seen (p = 0.03; p = 0.01). Ten minutes after smoking this decrease was recovered by half. This experiment confirms that one should prohibit smoking of cigarettes pre and postoperatively for optimal wound healing conditions. PMID- 1737222 TI - Prevention of blindness in giant cell arteritis by corticosteroid treatment. AB - Ninety-six patients with giant cell arteritis (GCA) seen from 1968 to 1985 were studied with regard to the starting dose of prednisolone and the development of serious ocular complications, which proved to be very few after treatment was started. Those starting on 20 mg of prednisolone or less daily fared at least as well as those starting on higher doses. Analysis of the literature does not support the belief that higher doses provide greater protection from blindness. PMID- 1737223 TI - Does a sterile urethritis occur in Reiter's syndrome secondary to gastrointestinal infection? PMID- 1737224 TI - A patient with rheumatoid arthritis and lymphoma. PMID- 1737225 TI - A rheumatologist in India. PMID- 1737226 TI - Bilateral adrenal infarction, hypoadrenalism and splinter haemorrhages in the 'primary' antiphospholipid syndrome. AB - We describe a patient with a 3-year history of recurrent deep vein thromboses (DVT) of the lower limbs, who developed adrenal insufficiency following withdrawal of warfarin therapy. Multiple splinter haemorrhages of the nail beds were evident, simultaneous with the development of adrenal infarction in the absence of infective endocarditis. CT scans of the adrenal glands were consistent with bilateral adrenal infarctions. The patient had persistently high titres of IgG anticardiolipin antibodies (aCL) over the previous 4 years in the absence of antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA) or extractable nuclear antigens (ENA). Thrombocytopenia and an intermittently positive Coombs' test had been noted. Previous episodes of DVT were associated with inadequate warfarin control and a period of warfarin resistance. He conforms to a diagnosis of a 'primary' antiphospholipid syndrome. PMID- 1737227 TI - Juvenile chronic arthritis and Wegener's granulomatosis. AB - We present a case of Wegener's granulomatosis in a teenage boy with systemic onset juvenile chronic arthritis. We discuss the implication of these two uncommon conditions coexisting in one patient. The recent characterization of the antineutrophil cytoplasmic antibody (ANCA) as a marker of small vessel vasculitis has helped in the differential diagnosis of pulmonary renal syndromes. PMID- 1737228 TI - IgM-rheumatoid factors measured by ELISA in non-rheumatoid sera: comparison of human and rabbit Fc fragments as antigens. PMID- 1737229 TI - Meninogococcal infection: diagnostic and therapeutic pitfalls. PMID- 1737230 TI - Plasma ascorbic acid concentrations in osteoporotic outpatients. PMID- 1737231 TI - Are nodules in RA the result of manual work? PMID- 1737232 TI - Confusional syndrome as the presenting form of calcium pyrophosphate dihydrate deposition disease. PMID- 1737233 TI - Interaction between the cell surface and the extracellular matrix. PMID- 1737234 TI - Effect of dominancy on severity in rheumatoid arthritis. AB - Joint use has been felt to increase the severity of rheumatoid synovitis. Ninety three patients with definite or classical rheumatoid arthritis (RA) were studied blind for clinical and radiological findings to see the effect of dominancy on the severity of the arthritis. The dominant side showed significantly greater total swelling scores (P less than 0.0001) and total tenderness scores (P less than 0.01). This was explained predominantly by greater severity of arthritis in dominant arms and hands. X-rays of the dominant hands and wrists showed more joint space narrowing (P less than 0.04) and erosion (P less than 0.01), but no differences in malalignment scores. There were no differences between dominant and non-dominant sides on frequency of intra-articular injections or use of splinting, but the dominant side received more surgical operations (P less than 0.02). PMID- 1737235 TI - Musculoskeletal pain in Omanis, and the relationship to joint mobility and body mass index. AB - In a house-to-house population survey of representative areas of Oman, 920 adults were examined and questioned about musculoskeletal pain. Back pain was reported in 42% of females and 25% of males, and knee pain in 15% of females and 18% of males. Hip pain occurred in only three females (0.6%) and one male (0.2%), which is consistent with a protective effect of squatting. In rural communities musculoskeletal pain was more common, and less anatomically localized. Joint mobility scores were higher in females than males and, at all nine sites included in the Beighton score, laxity was significantly more common in females than males. The scores declined with age, and were higher than those reported in Europeans and similar to those in Africans and Indians. Extreme joint laxity (score 7-9), seen only in females, was associated with increased symptoms in those aged 16-25 years. Body mass index was higher in females with back or knee pain than in those without such pain. In males, only knee pain was associated with higher body mass index. PMID- 1737236 TI - Is the appearance of rheumatoid nodules in a rheumatoid patient well controlled on methotrexate an indication to stop the drug? PMID- 1737237 TI - A generic health status instrument in the assessment of rheumatoid arthritis. AB - Seventy-three patients with RA were assessed by means of the Nottingham Health Profile (NHP), the Arthritis Impact Measurement Scales (AIMS) and a number of clinical measures. Patients with RA scored higher than controls on the NHP scales for energy, pain, mobility and sleep. Energy, pain, mobility and emotions scales of the NHP correlate significantly with other measures such as clinical assessments, matching scales of the AIMS and the Beck Depression Inventory, indicating satisfactory validity for the instrument with RA. Five of the six scales of the NHP are stable on retesting. The social scale of the NHP on the other hand does not correlate with the matching instrument of the AIMS and is relatively unstable over time. Measurement properties of generic health status instruments such as the NHP will require serious attention as they are increasingly used in evaluation studies. PMID- 1737238 TI - Vertebral osteoporosis in rheumatoid arthritis patients: effect of low dose prednisone therapy. AB - The effect of low dose prednisone therapy on spinal bone mass is controversial. We measured lumbar trabecular and cortical bone mineral density (BMD) in 74 rheumatoid arthritis (RA) patients by dual energy quantitative computerized tomography in a cross-sectional study. The presence of vertebral deformities was evaluated on a lateral spine radiograph. Patients who had never been treated with corticosteroids (n = 44) were compared with patients on long-term low dose (less than or equal to 10 mg/day) prednisone therapy (n = 30). After correction for confounding variables the lumbar BMD was highly significantly influenced by prednisone therapy in postmenopausal patients (estimated influence -31.2% on trabecular BMD and -37.2% on cortical BMD). Vertebral deformities were also significantly more frequent in prednisone treated postmenopausal patients. No negative effect of prednisone treatment could be demonstrated in male patients. In contradiction to previous reports we conclude that long-term prednisone therapy may be associated with development of spinal osteoporosis in postmenopausal RA patients, even when low doses are used. PMID- 1737239 TI - Prevention of vesicoureteric reflux by endoscopic injection. PMID- 1737240 TI - The persistent indwelling catheter. PMID- 1737241 TI - Vesico-coccygeal fistula revealing pelvic malakoplakia. PMID- 1737242 TI - Spontaneous rupture of the bladder in interstitial cystitis. PMID- 1737243 TI - Rate of development of ureteric obstruction in idiopathic retroperitoneal fibrosis (peri-aortitis). PMID- 1737244 TI - Re: Adverse urinary symptoms after total abdominal hysterectomy--fact or fiction? M.D. Griffith-Jones et al. Br. J. Urol., 67, 295-297, 1991. PMID- 1737245 TI - Re: The growing teratoma syndrome. G. M. Jeffery et al. Br. J. Urol., 67, 195 202, 1991. PMID- 1737246 TI - Agreement between clinical methods of measurement of urinary frequency and functional bladder capacity. AB - We assessed the agreement between 2 methods of data gathering of particular interest in urology: patient questionnaire and examination vs. frequency-volume charts. One hundred consecutive patients consulting our out-patient clinic were chosen for this study; 88 completed the study. Urinary frequency and bladder capacity were evaluated in each patient by using the above methods. The agreement between different methods of measurement was assessed by determining whether the 2 methods were interchangeable, a condition occurring if results of both methods fall within predetermined limits of variability. The results showed poor agreement between subjectively estimated urinary frequency and chart-determined urinary frequency. Moreover, different methods of measuring bladder capacity (endoscopic vs. chart) gave different results. Since chart-determined data are probably a more valid indication of urinary habits, we suggest that frequency volume charts should be used more often in the investigation and follow-up of patients with micturition disorders. PMID- 1737247 TI - Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. AB - Sixteen women whose ages ranged from 42 to 73 years (mean 57) and 2 men, aged 76 and 80 years respectively, were treated for urinary stress incontinence with transurethral implantation of submucosal glutaraldehyde cross-linked collagen (GAX); 15 females had had several continence operations previously and 1 female was totally incontinent following low anterior resection of the sigmoid colon for cancer. All but 2 patients received 8 ml GAX in a single operative session under general anaesthesia. Before implantation, patients underwent urodynamic evaluation, cystoscopy, urinary stress test and the two-thirds capacity pad weighing test. Post-operative evaluations were carried out after 3, 6 and 9 months and included urinary flow rate, urine analysis, residual urine determination and the two-thirds pad weighing test. The results were encouraging. After 3 months, 8/18 patients were cured, 7/18 had improved and 3/18 had failed to respond. Nine months post-operatively, 7 patients were still continent, 8 had improved and 3 remained unchanged. One of the improved group had a reinjection 18 months post-operatively and has been continent since then. We feel that GAX collagen injection is a safe and easy method for the treatment of urinary stress incontinence; it has no observable or measurable morbidity. PMID- 1737248 TI - Transurethral polytef injection for post-prostatectomy urinary incontinence. AB - This report deals with 720 incontinent males injected with Polytef paste. In all cases the incontinence resulted from some form of prostatic surgery. All patients had been incontinent for at least 1 year. Approximately 88% of patients incontinent from transurethral resection (TURP) were cured or improved; 74% of patients undergoing prostatectomy were improved, and approximately 67% of patients incontinent after radical prostatectomy were cured or improved. No major complications or clinical evidence of particle migration were observed. Our 20 plus years' experience with Polytef paste has shown it to be a safe and effective method for the treatment of post-operative male incontinence, with a high success rate. PMID- 1737249 TI - Is injected polytetrafluoroethylene (Polytef) carcinogenic? AB - Injectable polytetrafluoroethylene (Polytef) has been used in many patients for vocal cord augmentation and for the management of urinary incontinence since the early 1960s and non-injectable forms have been used for sutures, hernia repair, replacement of the stapes, hip prostheses, cardiac valves and vascular grafts. Since 1984, many children have been treated with subureteric Polytef injection for the management of vesicoureteric reflex. Its use in young patients has heightened the concern about particle migration and carcinogenesis, particularly in view of the fact that the substance may be in the patient for decades. The available evidence does not confirm a significant carcinogenic effect in humans; rather it suggests that, if there is a risk, it is extremely low. However, human specimens, taken decades after the implantation of Polytef, and long-term, non rodent animal experiments are needed to substantiate the probable safety of Polytef in children. PMID- 1737250 TI - Stamey-Martius procedure for severe genuine stress incontinence. AB - There are few options now available to treat patients with severe genuine stress incontinence caused by urethral failure. These patients usually have a low maximum urethral closure pressure (less than 20 cm of water) and anterior vaginal wall scarring caused by previous surgery. In 32 such patients we used the Martius fat pad insertion procedure, in addition to the Stamey procedure, and achieved a 91% symptomatic success rate over a mean 13-month follow-up period. Because of its simplicity, reliability and low morbidity, we recommend this procedure in this difficult group of patients before performing a sling procedure or insertion of an artificial urinary sphincter. PMID- 1737251 TI - Neurogenic bladder dysfunction in lumbar intervertebral disc prolapse. AB - Lumbar disc prolapse with urinary dysfunction is an uncommon condition. The clinical, pathological and follow-up details of 30 patients are presented. Detrusor recovery is rare and most patients are left with an areflexic bladder. Female patients with lumbar disc prolapse and an areflexic detrusor who strain to empty their bladders are likely to develop genuine stress incontinence. This may be managed by the early institution of intermittent self-catheterisation, which may reduce the need for incontinence surgery. PMID- 1737252 TI - Intravesical foreign bodies: five-year review. AB - All manner of foreign bodies have been extracted from the bladder. Introduction into the bladder may be through self-insertion, iatrogenic means or migration from adjacent organs. Extraction should be tailored according to the nature of the foreign body and should minimise bladder and urethral trauma. Complete extraction should also be confirmed by panendoscopy at the end of the extraction procedure. A 5-year review of our experience in this field has been conducted and the management and complications of intravesical foreign bodies are described. Of the 15 patients presenting to this department, 11 presented acutely and 4 presented with chronic symptoms due to complications which arose later. The possibility of an intravesical foreign body should be considered in any patient with chronic unexplained lower urinary tract symptoms. PMID- 1737253 TI - DNA analysis in predicting survival of irradiated patients with transitional cell carcinoma of bladder. AB - A total of 115 patients with invasive transitional cell carcinoma of the bladder underwent radical radiotherapy between 1975 and 1986 and were followed up until the end of 1990. Apart from routine clinical observations, flow cytometric DNA measurements made on fresh tumour material were available for analysis. Actuarial cancer-free survival controlling for response to treatment was analysed with the log-rank test, bivariate and multivariate analyses using Cox's stepwise regression model on probable prognostic factors. The overall actuarial 5-year cancer-free survival rate was 30%. Survival was significantly correlated with response to treatment: 59% for patients with complete regression and 5% for those with residual tumour. Prognostic factors that significantly correlated with death from cancer were advanced stage, large size, incomplete resection, ureteric obstruction, anaemia, carcinoma in situ grade 3 and occurrence of more than one aneuploid cell population. However, only 3 of these factors were of independent power in the multivariate analysis: stage, size and carcinoma in situ. Of 21 patients with a history of primary or secondary carcinoma in situ, 19 died from cancer during follow-up: 18 of the 21 patients had tumours that were aneuploid with more than one aneuploid cell population. It is concluded that curative radiotherapy can be successful only in patients with less advanced tumours assessed according to clinical stage and size, aneuploid tumours with not more than one aneuploid cell line, no carcinoma in situ, no ureteric obstruction, and in whom a complete transurethral resection of the exophytic tumour is possible. PMID- 1737254 TI - The use of a bladder pressure warning device during transurethral prostatic resection decreases absorption of irrigation fluid. AB - During a period of 4 weeks 102 patients underwent transurethral prostatic resection (TURP). Of these, 50 were randomly allocated to the use of an intravesical pressure device which warned the surgeon at a pressure elevation of 1.5 kPa. Ethanol (1%) was used as a marker in the irrigation fluid (glycine 2.2%), and absorption of ethanol-tagged irrigation fluid was detected by measurements in the expired air. In 28 patients absorption took place (in 8 of the 50 patients equipped with the warning device and in 20 of the 52 without the device). The greatest absorption was seen in the group without the device. No differences were found between the groups with regard to age, resected mass, resection time, resection speed, or haemorrhage. Patients who absorbed irrigation fluid were slightly older and bled more, and the resected mass was larger. The use of a pressure warning device reduces the amount of irrigation fluid absorbed and the number of patients who absorb irrigation fluid, and minimises the risk of the TUR syndrome. PMID- 1737255 TI - Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer. AB - In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton. PMID- 1737256 TI - Changes in detrusor innervation with relief of outflow tract obstruction. AB - In 10 patients with urodynamically proven outflow tract obstruction, detrusor biopsies were taken prior to and following relief of obstruction. The changes in detrusor innervation were compared following the relief of obstruction within the study group and also with an age-matched control group who were urodynamically normal. There was a significant reduction in detrusor innervation in the study group when compared with controls pre-operatively. Within the study group there was a significant increase in detrusor innervation in 8 patients following relief of outflow tract obstruction. Persistence of symptoms after prostatectomy may be explained by failure of detrusor reinnervation. PMID- 1737257 TI - Stress relaxation phenomenon in the healthy female urethra. AB - Following dilatation, urethral pressure declines over the next few seconds to a state of equilibrium. The stress relaxation parameter, Pt0.5, was defined as the relative pressure decrease 0.5 s after dilatation, where the pressures at 0.1 s and at the new equilibrium were set to 100% and 0% respectively. Pt0.5 was calculated from 171 urethral dilatations performed at each of 3 urethral sites of measurement in 10 healthy volunteers. It was found to be independent of the rate and size of urethral dilatation. It showed a fairly high reproducibility rate when repeated after 1 h and 1 week. Pt0.5 was calculated to approximately 60% with no variation along the urethra. The parameter is assumed to be useful in evaluating urethral sphincter function. Although the method can be performed without special urodynamic equipment, the frequency response of the pressure measurement system must be adequate. PMID- 1737258 TI - Urethral stress relaxation phenomenon in healthy and stress incontinent women. AB - Urethral stress relaxation was induced by sudden forced dilatation. The stress relaxation parameter, Pt0.5, was defined as the relative pressure decrease 0.5 s after dilatation, where the pressures at 0.1 s and at the new equilibrium were set to 100% and 0% respectively. Pt0.5 was calculated in 28 healthy and 30 women with genuine stress incontinence. Measurements were performed at the bladder neck, in the high pressure zone and in the distal urethra. The measurements showed that all along the urethra, Pt0.5 was statistically significantly greater in the healthy women than in the incontinent women, the greatest difference being found at the bladder neck. Although there was a slight overlap in values between the 2 groups, this parameter seems useful in differentiating between competent and incompetent urethral sphincters. PMID- 1737259 TI - Mullerian duct (prostatic utricle) cyst: diagnosis and treatment in subfertile males. AB - Mullerian duct cysts causing ejaculatory duct obstruction were discovered in 26 subfertile males; 21 patients had either azoospermia or very severe oligozoospermia. Characteristic seminal findings were a small volume ejaculate with acid pH and little or no fructose. The lesions were demonstrated by vasography and treated by endoscopic incision. After surgery there was a distinct improvement in volume of the ejaculate and sperm concentration in 10 patients, although another 10 patients continued to have azoospermia or severe oligozoospermia due to either persisting obstruction or secondary epididymal blocks. Eight female partners became pregnant. PMID- 1737260 TI - Treatment decision for stage I non-seminomatous germ cell tumours based on the risk factor "vascular invasion". AB - Surveillance has become an alternative treatment modality for stage I non seminomatous germ cell tumours with reported relapse rates of up to 30% in retrospective studies. Results obtained in our retrospective study showed vascular invasion in primary tumours to be the risk factor with the highest negative predictive value. Since January 1985 patients with stage I non seminomatous germ cell tumours have been stratified by the presence or absence of vascular invasion in the primary tumour: those without vascular invasion (n = 26; group A) were subjected to a rigorous surveillance programme, while those with vascular invasion (n = 22; group B) were given 2 chemotherapy courses of bleomycin, etoposide and platinum in the hope of preventing progression. Relapse rates were 3.8% and 9% in groups A and B, respectively. The pooled relapse rate for both groups A and B (n = 48) was 6.2% (3/48). After a mean follow-up time of 36 months 95.8% (46/48) of the patients were without evidence of disease. PMID- 1737261 TI - Non-invasive management of impotence with transcutaneous nitroglycerin. AB - Nitroglycerin plasters were applied to the penis in 10 impotent men and the erectile effect assessed. During laboratory testing all patients achieved an erectile response. Self-administration of nitroglycerin patches restored potency in 4 patients and was preferred to papaverine auto-injection by 3. Headache was a common side effect during initial administration. An attempt to treat impotence with nitroglycerin plaster seems worthwhile before starting extensive investigations or invasive treatment. PMID- 1737262 TI - Gastrocystoplasty in children. AB - We report our experience of gastrocystoplasty in 8 children (mean age 10.1 years) with compromised renal function (mean creatinine 186 mmol/l, mean glomerular filtration rate 39 ml/min/1.73 m2). Current follow-up ranges from 11 to 35 months (mean 21). The physiological outcome of the procedure has been excellent, with improved biochemical and urodynamic parameters in all cases. Six patients are off H2-receptor blockers and are asymptomatic. In 2 children we have encountered significant symptoms related to acid secretion in the bladder. Detailed investigations suggest that the excess aciduria is related to the size of the gastric patch in 1 patient. The second child underwent renal transplantation 5 months after gastrocystoplasty and it is postulated that his immunosuppressive regimen (which includes prednisolone) may be responsible for the increased acid secretion. It is concluded that gastrocystoplasty is a very satisfactory alternative to intestinal segment bladder enhancement in children with compromised renal function, but the size of the gastric patch is critical in determining the resultant acid secretion. Post-transplantation immunosuppressive therapy may increase acid production from the gastric patch; since the children most suitable for gastrocystoplasty are also those likley to require transplantation, this aspect requires further study. PMID- 1737263 TI - A male pseudohermaphrodite with Noonan's syndrome. PMID- 1737264 TI - Bilateral hydronephrosis secondary to breast carcinoma metastasising to the bladder. PMID- 1737265 TI - Seminal vesicle cyst, renal agenesis and epididymitis in a 50-year-old patient. PMID- 1737266 TI - Vesicosigmoid fistula as an incidental finding accompanying bladder cancer. PMID- 1737267 TI - Bacteriology of anal fistulae. AB - Anal fistulae are said to arise from cryptoglandular infection of the anal glands, which lie within the intersphincteric space. The type and virulence of the micro-organism responsible may determine whether an anal fistula develops. The microbiology of chronic anal fistulae has not been reported previously. Twenty-five consecutive anal fistulae were studied prospectively (eight intersphincteric fistulae, 12 trans-sphincteric fistulae, two suprasphincteric fistulae, one extrasphincteric fistula, one superficial fistula, one anovaginal fistula). There were 18 men and seven women, with a median age of 42 (range 22 71) years. Patients with Crohn's disease or acute anorectal suppuration were excluded. In 18 patients, 0.1 ml granulation tissue from the track of the fistula was obtained and processed within 4 h using standard microbiological techniques. Sixty-nine isolates representing at least 17 species were obtained. The predominant organisms were Escherichia coli (22 per cent), Enterococcus spp. (16 per cent) and Bacteroides fragilis (20 per cent). The majority of the growths were obtained only from enrichment. Bacteria from only one patient grew at a dilution of 10(3). Granulation tissue from 25 patients was processed for mycobacterial culture, and Mycobacterium tuberculosis was grown from one patient. No other mycobacterium was isolated. The chronic inflammation in anal fistulae does not seem to be maintained by either excessive numbers of organisms or organisms of an unusual type. PMID- 1737268 TI - Proctoscopic polyp delivery after colonoscopic polypectomy. PMID- 1737269 TI - Temporary loop ileostomy following restorative proctocolectomy. AB - A retrospective study compared the outcome of restorative proctocolectomy in patients who had a covering ileostomy (n = 53) with those who had no proximal stoma (n = 32). Those who had a loop ileostomy had a higher incidence of anastomotic leakage (21 per cent), pelvic abscess (32 per cent) and postoperative fistula (28 per cent) than those with no covering ileostomy (6, 12 and 12 per cent respectively). Intestinal obstruction occurred in 23 per cent of those with an ileostomy, compared with 6 per cent in those who had no stoma. The functional outcome was identical. PMID- 1737270 TI - Results of extensive surgery for liver metastases in colorectal carcinoma. AB - Hepatic resections were performed during the past 13 years on 31 patients with hepatic metastases from colorectal carcinoma. Of the 31 patients, 22 underwent lymph node dissection of the hepatic hilus. Ten patients underwent removal of recurrent lesions in the liver, lung, adrenal gland and brain after initial hepatic resection. The overall 5-year survival rate was 45 per cent. The outcome for six patients who underwent repeat hepatectomy after an initial hepatectomy was significantly better than for nine patients with unresectable recurrence (P less than 0.01). Six of the 22 patients who underwent lymph node dissection had nodes positive for tumour. Two of the six patients underwent repeat hepatectomy and are alive after 49 and 66 months. Three- and 4-year survival rates of patients with positive lymph nodes were both 40 per cent. Repeat hepatectomy and dissection of hilar lymph nodes improves prognosis in selected patients with hepatic metastases of colorectal cancer. PMID- 1737271 TI - Cholecystectomy and gallbladder conservation. PMID- 1737272 TI - Therapeutic perihepatic packing in complex liver trauma. AB - Packing for control of haemorrhage was used in 22 of 294 patients undergoing surgery for liver trauma over a 6-year period. The major indication for packing was transfusion-induced coagulopathy. Sixteen patients had blunt trauma and six penetrating trauma including five gunshot wounds; 19 patients had major right lobe injuries, three left lobe and five also had hepatic vein injuries. Packing provided definitive control of bleeding in 18 patients but four patients had recurrent bleeding due to hepatic artery injury (three) and hepatic vein injury (one); three required further surgery and bleeding was controlled in the fourth by selective hepatic artery embolization. Six patients died and in two of these recurrent bleeding, despite packs, was a contributing factor. Mean blood loss in the six patients who died was 18 (range 10-30) units, compared with 13.1 (range 8 30) units in survivors. Packs were removed from the 16 survivors at laparotomy at a mean of 3.1 days after insertion; six patients rebled during pack extraction and were successfully repacked. Major morbidity occurred in 12 of the 16 survivors. Seven patients developed intra-abdominal sepsis following packing, one of whom died. Therapeutic liver packing provides life-saving control of hepatic bleeding which is frequently aggravated by coagulopathy. This approach permits resuscitation in an intensive care unit and subsequent planned relaparotomy for retrieval of packs and further intervention as necessary. PMID- 1737273 TI - Hepatic transplantation in children using reduced size allografts. AB - The shortage of paediatric liver donors has led to the use of reduced size hepatic allografts. Between July 1987 and July 1990, 30 reduced size orthotopic liver transplantations were performed in 24 children aged between 3 months and 7 years. All patients were in advanced chronic or acute liver failure and were considered unlikely to survive for long enough for a size-matched donor to become available. The most common indication was biliary atresia. The median intraoperative blood loss was 75 (range 13-1015) ml kg-1. Nine patients have died and seven have undergone retransplantation, four successfully. Seven patients had portal vein hypoplasia with a high graft failure rate due to ischaemic infarction. There was significant morbidity from biliary tract complications, leading to further operations in four cases. The 1-year actuarial survival rate was 62 per cent. PMID- 1737274 TI - Hypercalcaemia associated with inflammatory pseudotumour of the spleen. PMID- 1737275 TI - Simple solution to the short oesophagus encountered at abdominal fundoplication. PMID- 1737276 TI - Effects of fine needle aspiration on subsequent mammograms. AB - The effects of fine needle aspiration on subsequent mammography were studied in a group of women who were referred with palpable breast lumps. Fifty-two women aged between 36 and 73 (median 53) years underwent mammography before and within 5 days of needle aspiration. Preaspiration and postaspiration mammograms were examined 'blind' by one radiologist. In ten cases, a difference was seen between the preaspiration and postaspiration films. In seven (aged 36-50 years) this was due to aspirated cysts. In three the differences were unexpected and were more significant, although the radiological diagnosis was not altered. If this proportion is extrapolated for a large number of patients then significant numbers of artifacts from fine needle aspiration might be seen on mammograms. It is possible that some might be interpreted falsely as malignant and some small cancers might be obscured. Women accepted mammography more readily before aspiration than after. PMID- 1737277 TI - Marking of specimens in patients undergoing stereotactic wide local excision for breast cancer. PMID- 1737278 TI - Outpatient treatment of non-lactational breast abscesses. AB - Eighteen consecutive patients with non-lactational breast abscesses have been treated by aspiration (ten patients), surgical drainage after application of local anaesthetic cream (seven patients) or a combination of aspiration and local anaesthetic cream drainage (one patient) combined with a 2-week course of either amoxycillin and clavulanic acid or cephradine and metronidazole. All abscesses resolved completely within 2 weeks of treatment and all 18 patients expressed satisfaction with the method of treatment used. The majority of patients with breast abscesses can now be managed as outpatients. PMID- 1737279 TI - Breast abscesses and cigarette smoking. AB - An 11-year retrospective review of women with breast abscesses presenting to a district general hospital was performed. A total of 122 women were identified with a breast abscess: 85 (70 per cent) with non-lactational abscesses and 37 (30 per cent) with an abscess in the puerperium. Six of 37 lactational and 24 of 85 non-lactational abscesses recurred. Sixteen mammillary fistulae developed, all following incision and drainage of non-lactational breast abscesses. Women with non-lactational breast abscesses were more likely to smoke cigarettes (P less than 0.005). Breast abscesses containing anaerobic bacteria were significantly more likely to occur in current cigarette smokers (P less than 0.05). Women with non-lactational breast abscesses who were heavy cigarette smokers were more likely to suffer recurrent abscesses (P less than 0.01). There was histological evidence of duct ectasia on biopsy in 25 women with non-lactational abscesses and 21 of 25 were current smokers. Mammillary fistulae developed more frequently in current smokers (P less than 0.03). Cigarette smoking is important in the natural history of non-lactational breast abscesses and may predispose to anaerobic breast infections and the development of mammillary fistulae. PMID- 1737280 TI - Pancreas and islet transplantation. PMID- 1737281 TI - Progress in the management of head injury. AB - Three 1-year surveys of head injury management spanning a 9-year period in a single regional centre are presented. There was a reduction in total numbers of head injury admissions after guidelines for admission and referral were implemented. More liberal use of computed tomography resulted in detection of a greater number of intracranial haematomas with the majority detected in non comatose patients. The early mortality rate in severe head injury fell from 45 per cent to 34 per cent despite referral of large numbers of patients with multiple injuries and a substantial proportion (12 per cent) of patients aged more than 70 years in whom outcome did not improve. Total occupied bednights and bednights occupied per surviving patient with severe head injury fell over the period of study. Care for patients with significant head injury should be based on regional neurosurgical units associated with trauma services. PMID- 1737282 TI - Early cardiorespiratory findings after severe blunt thoracic trauma and their relation to outcome. AB - This study examined the initial haemodynamic and oxygen transport patterns in 24 patients with severe blunt thoracic trauma in whom immediate monitoring with femoral and pulmonary artery catheters was required after admission to the intensive care unit. All patients required mechanical ventilation and were studied before receiving inhalational anaesthesia and within 12 h of injury. Two groups of patients were identified; nine patients (group 1) had an impaired left ventricular stroke work index (LVSWI) and 15 patients had a normal LVSWI (group 2). There were no significant differences in the abbreviated injury scale score for the chest, the total injury severity score, or the mean ages of the two groups. There were significant differences in stroke volume index, 32 versus 56 ml m-2 (P less than 0.001), and cardiac index, 3.2 versus 5.3 l min-1 m-2 (P less than 0.001), and therefore in oxygen delivery, 469 versus 852 ml min-1 m-2 (P less than 0.001), despite apparently adequate volume expansion using the same protocol and clinical criteria in both groups. Oxygen consumption was not significantly different in the two groups, 135 versus 157 ml min-1 m-2, because of a higher oxygen extraction ratio in group 1, 29 versus 19 per cent (P less than 0.001), and hence lower mixed venous oxygen saturation, 73 versus 82 per cent (P less than 0.02). Seven patients in group 1 died (78 per cent) compared with two in group 2 (13 per cent). Early depression of cardiac function is associated with poor outcome in patients with thoracic trauma, and measurements of oxygen transport variables may influence resuscitation and the timing of surgical procedures. PMID- 1737283 TI - Effect of transforming growth factor beta and basic fibroblast growth factor on steroid-impaired healing intestinal wounds. AB - A longitudinal intestinal wound model in the pig was used to assess the effect of parenteral steroids (betamethasone 12 mg 50 kg-1 intramuscularly twice daily) on breaking load. Steroid treatment significantly decreased the breaking load of wounds in the ileum and colon in comparison with wounds from saline-treated animals. In a further group of animals receiving steroids, paired longitudinal wounds were constructed. One wound of a pair was treated with a local application of transforming growth factor beta (TGF-beta) (5 micrograms per wound) or basic fibroblast growth factor (5 micrograms per wound) in a collagen suspension. The other wound was treated with a collagen suspension alone. Ileal wounds treated with TGF-beta were significantly stronger than collagen-treated controls at 7 days. The steroid-induced impairment of breaking load in intestinal wounds is partially reversed by a local application of TGF-beta in a collagen suspension at the time of surgery. PMID- 1737284 TI - Factors influencing the healing of distal amputations performed for lower limb ischaemia. AB - A total of 235 toes were amputated during 125 operations on 100 consecutive patients with lower limb ischaemia. The overall amputation wound healing rate for the series was 58.4 per cent and limb salvage was achieved in 66 patients. Toe amputation was performed under local anaesthesia in 57 cases and 32 (56 per cent) of these healed primarily, not significantly different from the healing rate of 41 (60 per cent) of 68 under general anaesthesia. Reconstructive arterial surgery was performed in conjunction with toe amputation in 39 patients; the healing rate with reconstruction was 32 (82 per cent) of 39, significantly better than the 41 (48 per cent) of 86 patients not undergoing bypass surgery (P less than 0.001). There was no difference in healing rates when comparing diabetic and non-diabetic patients. Multiple regression analysis demonstrated that reconstructive arterial surgery was the only factor which had an independent and significant influence on toe amputation healing. The use of local anaesthesia for distal amputation has no deleterious effects on wound healing. PMID- 1737285 TI - Early reoperation after major vascular surgery: a four-year prospective analysis. AB - Between 1 January 1985 and 31 December 1988, 1176 major vascular operations were performed on 1040 patients by the Oxford Regional Vascular Service, of which 136 (12 per cent) were reoperations within 30 days of the initial procedure (110 patients). Sixty-seven (49 per cent) of the reoperations were attempted revascularizations, 43 (32 per cent) were amputations, and surgery for bleeding accounted for 18 (13 per cent). Of the first reoperations 71 (65 per cent) were successful, but among the remaining 39 patients, 17 underwent 26 further reoperations, 15 of which were reoperations for revascularization. The 30-day mortality rate for patients undergoing one reoperation was 13 per cent; this rose to 35 per cent if more than one reoperation was performed. Early reoperation after major vascular surgery is common and carries a high operative mortality. This should be borne in mind when obtaining the informed consent of the patient. PMID- 1737286 TI - Doppler ultrasonographic localization of the cephalic vein: a new technique to simplify the insertion of central venous catheters. PMID- 1737287 TI - Laser-assisted angioplasty for arterial occlusion of the lower limb: initial results and follow-up. AB - A flashlamp-pumped pulsed dye laser operating at either 480 or 504 nm, coupled to an integral ball-tipped optical fibre, was used to recanalize occluded lower limb arteries. All channels created by the laser were augmented with balloon dilatation. We have treated 78 limbs in 71 patients; 46 limbs (59 per cent) had rest pain and 22 (48 per cent) of these had tissue loss. The median occlusion length was 18 (range 0.5-58) cm. Technical success was achieved in 58 limbs (74 per cent) with clinical success in 46 (59 per cent). Success rates fell with increasing length of occlusion. Two patients died in the perioperative period. A subgroup of 22 patients with marked discrete arterial calcification had a lower technical success rate than the subgroup without calcification (50 per cent versus 84 per cent, P less than 0.01). Both subgroups displayed a similar pattern of reclosure during follow-up. The cumulative patency rate after technical success was 67 per cent at 6 months and 45 per cent at 12 months. Forty-six (59 per cent) limbs avoided bypass surgery or amputation. Laser-assisted angioplasty may offer an alternative to femoropopliteal bypass, although the former procedure is not as durable. PMID- 1737288 TI - Low-dose intra-arterial thrombolysis in the treatment of occluded vascular grafts. AB - As the use of intra-arterial thrombolysis increases, its application to specific areas requires definition. The results of treatment of occluded vascular grafts are presented. Thrombolysis using streptokinase or tissue plasminogen activator was planned in the treatment of 18 occluded vascular grafts (five aortofemoral bifurcation grafts and 13 infrainguinal grafts). Two patients, both with infrainguinal occlusions, did not receive thrombolytic therapy and were considered failures of treatment. Successful lysis occurred in three of five aortofemoral grafts, in both infrainguinal vein grafts and in five of nine infrainguinal synthetic grafts. The overall success rate was approximately 60 per cent. Two-thirds of the patients required no intervention following successful lysis. Percutaneous transluminal angioplasty was not found to be a useful additional procedure. A review of the literature revealed that intra-arterial thrombolysis is significantly more successful in the treatment of suprainguinal graft occlusion than in infrainguinal occlusions, there being no difference between infrainguinal vein and synthetic grafts. Provided that the limb is viable and there are no contraindications, intra-arterial thrombolysis is a useful means of clearing occluded grafts. PMID- 1737289 TI - Haemodynamic significance of calf veins. PMID- 1737290 TI - Survival after local recurrence of soft tissue sarcoma. PMID- 1737291 TI - Suture technique and perianastomotic tumours. PMID- 1737292 TI - Selective uptake of glutamine in the gastrointestinal tract. PMID- 1737293 TI - Surgery for Crohn's disease in childhood. PMID- 1737294 TI - Aluminum and Alzheimer's disease. PMID- 1737295 TI - Aluminum and Alzheimer's disease. PMID- 1737296 TI - The right to remain psychotic. PMID- 1737297 TI - The right to remain psychotic. PMID- 1737298 TI - More problems with drug names. PMID- 1737299 TI - Familial combined hyperlipoproteinemia. PMID- 1737300 TI - Occupational therapy in the community. PMID- 1737301 TI - Covert influence? PMID- 1737302 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1737303 TI - Shut out flu. PMID- 1737304 TI - Generic drugs in Canada. PMID- 1737305 TI - Emergency care and the patient in the long-term care facility. PMID- 1737306 TI - Ethics of euthanasia. PMID- 1737307 TI - Ethics of euthanasia. PMID- 1737308 TI - Diatribe cloaked in scientific language. PMID- 1737309 TI - Invalidite temporaire et troubles emotifs [Temporary disability and emotional disorders. PMID- 1737310 TI - Health care technology assessment: linking science and policy-making. PMID- 1737311 TI - Small-area variations: what are they and what do they mean? Health Services Research Group. PMID- 1737312 TI - Pharmacologic management of refractory depression. AB - OBJECTIVE: To review published clinical trials of the pharmacologic management of refractory depression. DATA SOURCES: MEDLINE was searched for relevant articles published from 1983 to 1990. The bibliographies of review articles were searched for additional references. Studies of nonpharmacologic treatments, such as electroconvulsive therapy, were not included. STUDY SELECTION: Eleven studies were found that did not contain obvious digressions from several methodologic assessment criteria (adapted from the McMaster guidelines for the evaluation of clinical trials). Further scrutiny by a nonblind reviewer resulted in the selection of four reports that were considered acceptable. An assessment by a second reviewer, blind as to author, results and journal name, confirmed this judgement. DATA EXTRACTION: Data describing response to the treatments were extracted by a single (nonblind) reviewer. Post-hoc power estimates and 95% confidence intervals were calculated whenever possible. DATA SYNTHESIS: The efficacy of augmenting an antidepressant regimen with lithium carbonate, triiodothyronine or reserpine was not supported by findings from the clinical trials reviewed. However, many trials with negative results lacked adequate statistical power to exclude the possibility of the drug's efficacy. The use of a monoamine oxidase inhibitor was supported by the one study that met the review's methodologic criteria. However, this study was not conducted under double-blind conditions. CONCLUSION: The generally recommended strategies for the pharmacologic treatment of refractory depression are not supported by methodologically sound studies. PMID- 1737313 TI - Nature of the clinical difficulties of first-year family medicine residents under direct observation. AB - OBJECTIVE: To determine and classify the difficulties of first-year family medicine residents observed during clinical interviews. DESIGN: Retrospective, descriptive study. SETTING: Family practice unit at a teaching hospital. PARTICIPANTS: Forty-seven of the 56 first-year family medicine residents during their 2-month compulsory rotation in ambulatory family medicine, between July 1983 and December 1988, and 4 physicians who supervised the residents. MAIN OUTCOME MEASURE: The residents' difficulties noted on the observation forms. MAIN RESULTS: A total of 1500 difficulties were observed during 194 interviews, an average of 7.7 (standard deviation 5.2) per interview. There were 167 different difficulties, which were classified into seven categories (introduction, initial contract, body of the interview, techniques and organization, interpersonal aspects, final contract and miscellaneous) and 20 subcategories. The 17 most frequently noted difficulties accounted for 40% of the total. CONCLUSIONS: The results constitute a useful starting point for developing a classification of residents' difficulties during clinical interviews. We believe that the list of difficulties is applicable to residents at all levels and in other specialties, especially in ambulatory settings. The list can be used to develop learning materials for supervisors and residents. PMID- 1737314 TI - Neonatal congenital diaphragmatic hernia and extracorporeal membrane oxygenation. AB - OBJECTIVE: To describe the outcome of infants with congenital diaphragmatic hernia (CDH) presenting early who were referred for possible extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective descriptive study. SETTING: Neonatal Intensive Care Unit of the Royal Alexandra Hospital, Edmonton. PATIENTS: Fifteen infants referred to our program since its introduction, in February 1989; 13 received ECMO. The criterion for ECMO was the presence of an oxygen index of more than 40 on three occasions within 2 hours. INTERVENTION: ECMO was performed by means of cannulation of the right carotid artery and jugular vein for 111.0 hours on average. RESULTS: In 5 of the 13 infants who underwent ECMO the procedure was performed after surgical repair; all were successfully weaned off ECMO, and the cannula was removed without incident. In the remaining eight ECMO was started before surgical repair; of the six who received it during repair four ultimately survived. None of the previously described predictors of outcome for CDH, including diagnosis before 25 weeks' gestation (in six cases), were useful in determining the survival of the patients. Bleeding was the most common complication and cause of death. CONCLUSION: ECMO is associated with survival in infants with CDH who fail to respond to conventional therapy and who have a poor prognosis according to previously established criteria. PMID- 1737315 TI - Effects of a medical team coordinator on length of hospital stay. AB - OBJECTIVE: To determine the effect of a medical team coordinator (MTC) on the length of stay in a teaching hospital. DESIGN: Randomized controlled trial. SETTING: Two of four general medical clinical teaching units (CTUs). PATIENTS: Patients admitted to the CTUs between July and October 1990 except those who were admitted directly to an intensive care unit or whose death was expected within 48 hours. The 267 patients were randomly assigned to receive either standard medical care or standard medical care plus MTC services. INTERVENTION: The MTC was a baccalaureate nurse whose role was to facilitate administrative tasks such as discharge planning, to coordinate tests and procedures, and to collect and collate patient information. MAIN OUTCOME MEASURES: Length of hospital stay. A subgroup of 40 patients was asked to complete a brief survey on medical care information and satisfaction. RESULTS: The MTC intervention reduced the mean length of stay by 1.97 days (p less than or equal to 0.04, 95% confidence interval [CI] 1.02 to 2.92 days). Subanalysis by diagnostic group revealed that most of this effect was in an ill-defined group of disorders. In the survey more patients in the MTC group than in the other group reported being satisfied with their medical care (89% v. 62%; p less than or equal to 0.05, 95% CI 2% to 52%). CONCLUSIONS: The services of an MTC help to reduce the length of hospital stay for some groups of patients. Further research is necessary to examine which components of the MTC intervention are most effective and in what conditions. PMID- 1737316 TI - Update: transmission of HIV infection during invasive dental procedures. PMID- 1737317 TI - Obesity and coronary heart disease. PMID- 1737319 TI - Eating the leek. 1912. PMID- 1737318 TI - The use of BCG. 1948. PMID- 1737320 TI - Doctors can improve on way they deliver bad news, MD maintains. Interview by Evelyne Michaels. PMID- 1737321 TI - Alberta college latest to tackle issue of physician-related sexual abuse. PMID- 1737322 TI - Medicine without moralizing is the aim of Montreal's "street doctors". PMID- 1737323 TI - MDs angry as most pharmacies continue to sell "number one cause of death". PMID- 1737324 TI - Cases involving "20th-century diseases" start landing in British courts. PMID- 1737325 TI - Canadian health care system source of lively debate in journals. PMID- 1737326 TI - CMA and other members of lobby group develop five-point plan for Canada's health care future. PMID- 1737327 TI - MDs, nurses play major role in success of "sexuality clinics" at Ottawa high schools. PMID- 1737328 TI - STDs' economic impact felt in both developed and Third World countries, meeting told. PMID- 1737329 TI - Patients' right to die becoming major issue for MDs and MPs. PMID- 1737330 TI - Bill C-203 is a worthwhile effort but contains some flaws. PMID- 1737331 TI - Disseminating tumor cells and their interactions with leukocytes visualized in the brain. AB - Brain tumors are increasingly prevalent. Recent advances focus attention on individual, disseminated tumor cells that cannot be imaged or eliminated. Cells of the immune system may be ideally suited to attack individual tumor cells, but more basic understanding is needed. We describe a rat model, using the lacZ reporter gene, that allows identification of individual tumor cells, and tumor leukocyte interactions in vivo. The model demonstrates how widely tumor can disseminate, without secondary tumorigenesis or recruitment of nonneoplastic cells. It demonstrates that leukocytes have access to disseminating tumor. Among its many applications, this work lays a foundation for developing cell-mediated immunotherapy against individual brain tumor cells. PMID- 1737332 TI - Interleukin 9 is expressed by primary and cultured Hodgkin and Reed-Sternberg cells. AB - We show by mRNA hybridization analysis and immunostaining using a mouse monoclonal antibody (moAb) to recombinant human interleukin 9 (IL-9) that both primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells produce IL-9 transcripts and protein and express surface binding sites for IL-9. In addition, the growth of H-RS cells obtained from the HDLM-2 line (abundantly producing IL-9 transcripts) was significantly inhibited when anti-IL-9 moAb or an IL-9 antisense oligodeoxyribonucleotide was added to cultures. Excess addition of recombinant human IL-9 relieved the effects of anti-IL-9 moAb on HDLM-2 growth. Growth of H RS cells of the KM-H2 line, which displays only low amounts of IL-9 detectable upon hybridization of polyadenylic acid-selected RNA only, was not affected by anti-IL-9 moAb. The proliferative capacity of KM-H2 cells in soft agar and liquid suspension cultures was, however, augmented at least 3-fold when cells were exposed to recombinant human IL-9. In conclusion, our results show that IL-9 is expressed by H-RS cells and point to a possible role of this molecule as a growth factor for these cells. PMID- 1737333 TI - Infrequent p53 mutation in mouse tumors with deregulated myc. AB - An invariant genetic lesion in mouse plasmacytomas is deregulated expression of c myc as a consequence of chromosomal translocation. However, retroviral and transgenic studies suggest that additional genetic lesions may contribute to the genesis of plasmacytomas. The p53 tumor suppressor gene is a likely contributor to this genetic lesion, since there is a high incidence of p53 mutation in Burkitt's lymphomas and B-ALL (L3), both of which contain translocations involving c-myc analogous to those in plasmacytomas. In addition, p53 has been shown to be a transcriptional modulator of c-myc expression. In a survey of 27 mouse plasmacytomas by single-strand conformation polymorphism, we identified a single mutation (3.7% incidence), suggesting that p53 lesions are not frequent contributors to plasmacytomagenesis. A similar study of macrophage-monocyte tumors generated by a c-myc-containing retrovirus also indicates a lack of p53 involvement in deregulated c-myc expression. These results suggest that the specific maturation stage of transformed B-lymphocytes, independent of c-myc deregulation, may be the critical factor which determines the involvement of mutant p53. PMID- 1737334 TI - Re: R. Grundel and H. Rubin, Effect of interclonal heterogeneity on the progressive, confluence-mediated acquisition of the focus-forming phenotype in NIH-3T3 populations. Cancer Res., 51:1003-1013, 1991. PMID- 1737335 TI - A new form of cytochrome P-450 responsible for mutagenic activation of 2-amino-3 methylimidazo[4,5-f]quinoline in human livers. AB - Antibodies to P-450IA2 strongly inhibited the mutagenic activation of 2-amino-3 methylimidazo [4,5-f]quinoline (IQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate but not aflatoxin B1 in human liver microsomes. The anti-rat P-450IA2 antibodies were capable of recognizing two proteins which show different mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human liver microsomes. A new form of cytochrome P-450 (designated P-450-HM4) cross reactive with anti-rat P-450IA2 antibodies showing that the smaller molecular weight was purified from human liver microsomes by means of the fast-performance liquid chromatography system. The molecular weight of P-450-HM4 was estimated to be 49,000, which was apparently different from that of P-450PA (human P-450IA2). The antibodies to P-450-HM4 did not cross-react with P-450PA (human P-450IA2) but inhibited to various extents the mutagenic activation of IQ in microsomes from human livers. In addition, P-450-HM4 showed significant mutagen-producing activity from IQ in a reconstituted system. Together with these and other results reported previously, it is concluded that at least two forms of cytochrome P-450 [P-450-HM4 and P-450PA (human P-450IA2)] are involved in the mutagenic activation of IQ in human liver. PMID- 1737336 TI - Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. AB - The purpose of this study was to elucidate a possible immune response to tumor cells mediated by tumor-infiltrating lymphocytes (TIL) in lung cancer. In flow cytometry, the majority of T-cells of TIL were CD45RA-, CD45RO+, and CDw29high, and expressed HLA-DR. The expression of interleukin 2 receptor beta chain increased in both CD4+ and CD8+ TIL compared with both types of T-cells in peripheral blood. These results indicate that the major population of TIL is activated memory T-cells. The TIL preparation, which was usually contaminated with 5 to 10% tumor cells, did not exhibit any response in autologous mixed lymphocyte-tumor culture even in the presence of interleukin 2 (IL-2) in all five cases tested. Although purified T-cells from TIL showed the positive response in only 1 of 10 cases tested without addition of IL-2, it occurred in 7 of 10 cases in the addition of a low concentration of IL-2. The IL-2-dependent response to irradiated autologous tumor cells was suppressed when nonirradiated autologous tumor cells were added to the culture. Culture supernatants of four lung cancer cell lines and freshly prepared lung cancer cells obtained from 6 cases exhibited suppressive activity against anti-CD3 antibody-induced mitogenesis of peripheral blood mononuclear cells from healthy donors. We suggest that, taken together, (a) the major population of TIL in lung cancer are activated memory T-cells, and they include tumor-reactive ones, and that (b) the function of the TIL is impaired by unavailability of IL-2 and/or by suppression due to lung cancer cell-derived factor(s). PMID- 1737337 TI - Parental occupation and childhood astrocytoma: results of a case-control study. AB - Parental occupations were investigated as possible risk factors for astrocytoma, the most frequently occurring brain tumor in children. A case-control study of 163 pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of eight hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random-digit dialing and were matched to cases on age, race, and telephone area code. Occupations before the child's conception, during the pregnancy, and after the child's birth were studied separately. We did not observe any strong associations. Significantly more fathers of cases were electrical or electronic repairmen, a subgroup of an occupational category previously associated with increased risk. An excess of case mothers employed as nurses was observed, which was significant for mothers of children diagnosed before 5 years of age. Elevated although not significant odds ratios were observed for some white collar and professional occupations in case parents; for paternal exposure to paint and paternal occupation in the paper and pulp mill industry, both in the period after the child's birth; and for maternal occupation as a hairdresser. The lack of strong associations may have resulted from low statistical power for some job groupings. Our study, unlike previous studies, focused on a single type of brain tumor: childhood astrocytoma. Thus our results suggest that some parental occupations associated with childhood brain tumors in previous studies may not be risk factors for childhood astrocytoma. PMID- 1737338 TI - Reversibility of catechol-induced rat glandular stomach lesions. AB - The potential reversibility of glandular stomach lesions induced by the clastogen, catechol, was examined in groups of male F344 rats treated continuously with 0.8% catechol in the diet for 12, 24, 48, 72, or 96 weeks. After a return to basal diet for 84, 72, 48, 24, and 0 weeks, respectively, the animals were killed for histopathological examination. Incidences of submucosal hyperplasia, adenomas and adenocarcinomas, average number of tumors per rat, and the size of tumors in rats treated with catechol for 12, 24, 48, 72, and 96 weeks increased time dependently. After cessation of catechol treatment, although average number of tumors per rat slightly decreased, the size of tumors tended to increase. Labeling indices in both tumorous and nontumorous areas decreased after cessation of catechol treatment. The results thus indicate that whereas some submucosal hyperplasias or adenomas may regress, others have the potential to develop into adenomas or adenocarcinomas. However, tumor growth does depend to a certain extent on continued catechol treatment. PMID- 1737339 TI - NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. AB - NAD(P)H:quinone oxidoreductase (DT-diaphorase; DTD) is an obligate two-electron reductase which may play a role in the bioactivation of antitumor quinones such as mitomycin C (MMC). We studied 10 colon carcinoma cell lines showing different levels of DTD activity (range, 0-3447 nmol/min/mg protein), as measured by the reduction of dichlorophenolindophenol. Expression of the NAD(P)H:quinone reductase gene (NQO1), which codes for the DTD enzyme, as measured by a polymerase chain reaction amplification technique was then correlated with enzymatic activity in all cell lines. HT-29 cells, which have intermediate DTD activity (769 +/- 144 nmol/min/mg protein, mean +/- SD) and are sensitive to MMC, showed high NQO1 expression relative to beta-actin (taken as 100% here for comparative purposes). BE cells which have no detectable DTD activity and are resistant to MMC showed moderate NQO1 expression (91% of HT-29). RNA single strand conformational polymorphism analysis and subsequent sequencing of BE complementary DNA revealed a C to T mutation in the NQO1 complementary DNA. This confers a proline to serine substitution in the amino acid sequence of the protein. Additionally, HCT-116 cells showed both moderate DTD activity (390 +/- 41 nmol/min/mg protein) and NQO1 expression (41% of HT-29), while resistant subclones of these cells, exposed to MMC during 11 and 44 weeks, showed low gene expression (5 and 9% of HT-29 respectively) and enzymatic activity (11 +/- 6 and 36 +/- 16 nmol/min/mg protein). These results support the ideas that reductive activation of MMC by DTD may be important in the cytotoxicity of MMC and that polymerase chain reaction may be a useful technique for quantitating the relative expression of genes in human tumors. PMID- 1737340 TI - Human uterine endometrial adenocarcinoma: characteristic acquirement of synthetic potentials for II3SO3-LacCer and ganglio series sulfoglycosphingolipids after transfer of the cancer cells to culture. AB - The acidic glycosphingolipid composition of human uterine endometrial adenocarcinoma was compared with those of normal uterine endometrium at the proliferative and the secretory phases. Upon chemical composition analysis, no significant transformation-associated change of these glycolipids was observed. However, when cancer cells from the patients with human uterine endometrial adenocarcinoma were transferred to culture, the composition of glycosphingolipids, particularly sulfoglycosphingolipids, was significantly altered after the 70th doubling time. I3SO3-GalCer, which was contained in the original tissues of uterine endometrial adenocarcinomas, disappeared completely from the cultured cells at the 70th doubling time, whereas II3SO3-LacCer and ganglio series sulfoglycosphingolipids, which were originally contained in a trace amount or not present at all in the cancer tissues, became the major components in the total acidic glycosphingolipids in the cultured cells. Also, among cell lines established from several gynecological cancers, which include uterine cervical squamous carcinoma, uterine endometrial adenocarcinoma, ovarian clear cell carcinoma, choriocarcinoma, uterine sarcoma, ovarian sarcoma, and vulvar melanoma, only those cells derived from uterine endometrial adenocarcinoma expressed II3SO3-LacCer and ganglio series sulfoglycosphingolipids and the synthetic activities of these sulfoglycolipids, indicating that uterine endometrial adenocarcinoma cells characteristically lose the sulfotransferase to GalCer and acquire the sulfotransferase to LacCer after being transferred to culture in vitro. Thus, the unique sulfoglycosphingolipids and sulfotransferase are useful markers for the characterization of uterine endometrial adenocarcinoma among human gynecological cancers. PMID- 1737341 TI - Localization of shed human tumor gangliosides: association with serum lipoproteins. AB - Tumor gangliosides are biologically active (immunosuppressive and tumor enhancing) cell surface molecules which are shed into the circulation in vivo. However, the mechanism of transport of these molecules (i.e., in solution or bound to proteins or other lipids) is not known. To resolve this question we traced, by direct chemical detection, the serum localization of a specific human tumor ganglioside, GD2, shed by neuroblastoma cells. Sera from patients with tumors were separated into the lipoprotein fractions [very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein] and lipoprotein-depleted serum. All three lipoprotein fractions contained GD2. 73% of the total GD2 was present in the LDL fraction, while very low-density lipoprotein and high-density lipoprotein contained 21 and 6%, respectively. Significantly, lipoprotein-depleted serum, which would contain both albumin-bound and free ganglioside, was devoid of GD2. Thus, shed neuroblastoma tumor gangliosides are exclusively associated with the serum lipoprotein (and predominantly LDL) fractions in vivo. These findings have implications for the immunological detection of these molecules and the development of approaches to their removal. PMID- 1737342 TI - Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma associated antigen. AB - GA733-2 is a monoclonal antibody-defined, 40-kDa glycoprotein antigen that is associated with carcinomas of various origins. Hydrophobicity analysis of the protein sequence predicted by complementary DNA (cDNA) has suggested that the GA733-2 antigen is a type I membrane protein. In this study, the polymerase chain reaction was used in a strategy to omit cDNA sequences for the transmembrane and cytoplasmic domains, thereby converting the extracellular domain into a secretory protein. Full-length and truncated cDNAs were cloned into the baculovirus transfer vector pVL1392 and introduced into Autographa californica nuclear polyhedrosis virus by homologous recombination. The full-length cDNA baculovirus recombinant directed the expression of a 40-kDa glycoprotein that was confined to infected Spodoptera frugiperda cells, whereas cells infected with the truncated cDNA baculovirus recombinant abundantly secreted a 31-kDa glycoprotein into the culture medium. Recombinant secretory antigen displayed an in vitro immunoreactivity to monoclonal antibody and an in vivo immunogenicity in mice that were similar to native antigen. The facile purification of mg quantities of carcinoma-associated antigen will enable an evaluation of its immunogenicity in cancer patients. PMID- 1737343 TI - Ammine/amine platinum(IV) dicarboxylates: a novel class of platinum complex exhibiting selective cytotoxicity to intrinsically cisplatin-resistant human ovarian carcinoma cell lines. AB - Using a panel of six human ovarian carcinoma cell lines varying by two orders of magnitude in terms of cisplatin cytotoxicity, we have investigated the in vitro antitumor activity of a series of novel alkylamine ammine dicarboxylatodichloroplatinum(IV) complexes of the general formula c,t,c [PtCl2(OCOR1)2NH3(RNH2)]. A clear relationship existed between increasing the number of carbons in the R1 substituent and increasing cytotoxicity up to R1 = C5H11. In terms of changing the R group, maximum cytotoxic effects were conferred by alicyclic substituents. Furthermore, increasing the alicyclic ring size from cyclobutane through to cycloheptane resulted in increasing cytotoxicity. The agents with longer axial chains (e.g., JM300, R = cyclohexyl, R1 = C6H13) were significantly more cytotoxic than cisplatin and, moreover, exhibited a selective cytotoxic effect against the most intrinsically cisplatin-resistant cell lines (e.g., for HX/62, cisplatin 50% inhibitory concentration, 12.6 microM; SKOV-3, cisplatin 50% inhibitory concentration, 4.4 microM and 41 M; cisplatin 50% inhibitory concentration, 0.23 microM; JM300 was 840-, 440-, and only 34-fold more active, respectively). The dicarboxylates JM221 (R = cyclohexyl, R1 = C3H7) and JM244 (R = n-propyl, R1 = C6H5) also retained activity against a 4-fold cisplatin-acquired resistant variant of the 41M cell line. At least part of the increased cytotoxicity of the dicarboxylate, JM221, over cisplatin appeared to be attributable to an increased intracellular accumulation. This novel class of platinum compound represents a valuable lead in the development of a "third generation" agent capable of exhibiting activity against clinical disease currently resistant to cisplatin. PMID- 1737344 TI - Identification of a human tumor-derived lipolysis-promoting factor. AB - Our previous studies have demonstrated the production and release of a tumor derived factor that promoted lipolysis in normal adipocytes. We further demonstrated that this in vitro lipolysis was correlated with the in vivo loss of total carcass lipids induced by the presence of the same tumor. This study identified and isolated this "lipolysis-promoting" factor (LPF), released into the extracellular environment (conditioned media) by the human A375 melanoma cell line, which appears to be responsible for the previously demonstrated induction of in vitro and in vivo lipolytic activity. Unlike previously described non-tumor derived molecules, such as tumor necrosis factor-alpha/cachectin, which have been implicated in cancer cachexia, the LPF induces alterations in lipid metabolism similar to those observed in cancer patients. The biochemical nature of human tumor-derived LPF appears to be a heat-stable molecule with an apparent molecular weight of approximately 6000. The lipolysis-promoting activity was trichloroacetic acid precipitable, but not precipitable with protamine sulfate or extractable with chloroform:methanol. Its activity appears to be resistant to enzymatic treatments with protease K, trypsin, Pronase, RNase, and DNase, as well as to periodate oxidation. Immunochemically, LPF appears to be distinct from tumor necrosis factor-alpha/cachectin. Furthermore, in contrast to the mechanism of action of tumor necrosis factor-alpha/cachectin, the mechanism of "lipolysis promotion" by LPF appears to be by the induction of cellular lipase activity. PMID- 1737345 TI - The fate of antibodies bound to the surface of tumor cells in vitro. AB - The fate of monoclonal antibodies binding to the surface of human tumor cells in vitro was investigated. Seven antibodies, labeled with 125I, were tested on four cell lines, which included a melanoma and carcinomas of the ovary, kidney, and lung. The antibodies were selected only by the criterion that they not be rapidly internalized via coated pits, so that they would be representative of most antibodies reacting with cell surface antigens. After allowing binding during a 2 h incubation, unbound antibody was removed, and the release of intact or degraded antibody in the supernatant was monitored. The data demonstrate that most bound antibody was gradually degraded and released from the cell over a 2-3-day period, probably via internalization, while only a small fraction, less than 20% for most antibodies, appeared to dissociate intact. One exceptional antibody, MW207, dissociated largely intact. The release of intact antibody was virtually complete within 4 h, and radioactivity released after this time was predominantly in degraded form. These results demonstrate that antibody binding to the surface of viable cells must in general be considered irreversible, and hence the concept of affinity is not applicable. Since an Fab fragment of one of the antibodies dissociated rapidly, such irreversible binding appears to require bivalent attachment. Another conclusion of this study is that most antibodies binding to the cell surface are gradually internalized, which we suggest is due to the normal turnover of cell surface constituents via non-clathrin-dependent endocytosis. Several experimental approaches indicated that a large fraction of antibody retained by the cells, for at least 2 days after binding, was present at the cell surface. PMID- 1737346 TI - Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial. AB - Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5' oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5' oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity. PMID- 1737347 TI - The combined effects of dietary fat, protein, and energy intake on azoxymethane induced intestinal and renal carcinogenesis. AB - Two 3 x 3 factorial experiments were conducted to examine the effects of dietary protein (8, 16, and 32% of energy from casein) and dietary fat (12, 24, and 48% of energy from corn oil) on the initiation and promotion of azoxymethane-induced carcinogenesis in rats. For the initiation study, 33 weanling male Sprague-Dawley rats were randomized to each of nine diets fed ad libitum. Azoxymethane was administered s.c. between the fourth to sixth weeks of feeding, providing a total dose of 6 mg/100 g body weight. All rats were subsequently fed a common diet containing 16% energy from protein and 24% energy from fat for an additional 30 to 38 weeks. For the promotion study, all rats were fed a common diet containing 16% of energy from protein and 12% of energy from fat until the completion of azoxymethane administration, when 33 rats were randomized to each of nine diets varying in fat and protein content and fed these diets until sacrifice. Low protein diets during the initiation phase were associated with increased risk of renal adenocarcinomas (P less than 0.001) and mesenchymal (P = 0.005) malignancies. No other statistically significant relationships were found between the levels of dietary fat or protein and the prevalence of malignant lesions of the small intestine, colon, or kidney in either the initiation or promotion study (although polypoid adenocarcinoma of the colon increased suggestively from 13 to 19 to 26% of rats with increasing dietary protein during initiation). Results of a multiple logistic regression analysis, combining both studies, showed that ad libitum energy intake was significantly associated with intestinal carcinogenesis. The odds of finding an intestinal adenocarcinoma increased by 6.2 +/- 2.6% (SE) for each additional kilocalorie of mean daily ad libitum intake (P = 0.014). The quintile of rats which consumed the least averaged 60 kcal/day, while the most voracious quintile averaged 74 kcal/day. This 14 kcal/day difference in mean ad libitum intake corresponded to more than a doubling (146% increase) of the odds of developing an intestinal adenocarcinoma. These studies suggest that ad libitum energy intake is a critical factor modulating experimental colon carcinogenesis. PMID- 1737348 TI - Resistance to cytolysis by tumor necrosis factor alpha in malignant gynecological cell lines is associated with the expression of protein(s) that prevent the activation of phospholipase A2 by tumor necrosis factor alpha. AB - Although there are a limited number of cell lines that are sensitive to cytolysis by tumor necrosis factor alpha (TNF alpha), the vast majority are resistant. The analysis of TNF alpha-sensitive cells has shown that phospholipase A2 is activated by TNF alpha in these cells and that the activity of phospholipase A2 is required for their cytolysis. Many cell lines that are resistant to TNF alpha mediated cytolysis are dependent on the maintenance of protein synthesis for their resistance. We have recently shown that this is also true for TNF alpha resistant cell lines derived from cervical (ME-180 and SiHa) and ovarian (SK-OV-3 and OVCAR-3) carcinomas, in that they are sensitive to cytolysis by TNF alpha only in the presence of protein synthesis inhibitors. Here we show that the TNF alpha-mediated cytolysis of these resistant cell lines in the presence of the protein synthesis inhibitor emetine is similar to that of sensitive cells, in that cytolysis is inhibited by the inhibitors of phospholipase A2. The measurement of the release of radiolabeled material from cervical and ovarian carcinoma cell lines prelabeled with [3H]arachidonic acid showed that not only was phospholipase A2 required for the cytolysis of these cells by TNF alpha in the presence of protein synthesis inhibitors, but more importantly, phospholipase A2 was not activated by TNF alpha unless protein synthesis was inhibited. These results indicate that a protein synthesis-dependent resistance mechanism expressed by these cell lines blocks TNF alpha-mediated cytolysis by preventing the activation of phospholipase A2 by TNF alpha. PMID- 1737349 TI - cis-Diamminedichloroplatinum(II) induces c-jun expression in human myeloid leukemia cells: potential involvement of a protein kinase C-dependent signaling pathway. AB - cis-Diamminedichloroplatinum(II) (CDDP) is a chemotherapeutic agent known to inhibit DNA, RNA, and protein synthesis. The cytotoxicity of this drug is thought to result from the formation of DNA intrastrand cross-links. The present work demonstrates that treatment of human myeloid leukemia cells (HL-60, U-937, and KG 1) with CDDP is associated with increased expression of the c-jun gene and that this effect is related to activation by a transcriptional mechanism. The results also demonstrate that treatment with CDDP is associated with increases in protein kinase C (PKC) activity. Furthermore, the finding that pretreatment with H7, an inhibitor of PKC, abrogates the effect of CDDP on c-jun expression suggested the involvement of PKC in this process. Down-regulation of PKC by prolonged pretreatment with 12-O-tetradecanoylphorbol-13-acetate was also associated with inhibition of CDDP-induced c-jun expression. The results further demonstrate that there is a temporal relationship between the CDDP-induced increase in c-jun expression and the occurrence of internucleosomal DNA cleavage characteristic of programmed cell death. These findings suggest that c-jun may be involved in the cellular response to DNA-damaging agents, such as CDDP, and that this effect may be mediated by a PKC-dependent pathway. PMID- 1737350 TI - Radiation-induced apoptosis in a murine T-cell hybridoma. AB - Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X radiation, 43 degrees C heat shock, A254 light, and hydrogen peroxide. In 5-Gy exposed cells, a radiation-induced G2 phase cell cycle progression block was maximum by 8 h. The cells began to escape this progression block by 10 h. Nuclear DNA fragmentation and uptake of the vital dye trypan blue began at 12 and 14 h, respectively, and were complete by 28 h. X-radiation-induced cell death was diminished when cells were irradiated in the presence of dimethyl sulfoxide, indicating that cell death was induced by oxidative cell damage. Substitution of nuclear DNA with bromodeoxyuridine enhanced death in cells exposed to either X radiation or A310 light, indicating that apoptosis could be induced by DNA damage. The results are consistent with radiation-induced apoptosis being stimulated by oxidative DNA damage. DNA damage stimulates a long-lived signal which controls the expression of apoptosis. Apoptosis is expressed in the G1 phase of the cell cycle subsequent to the cell irradiation. PMID- 1737351 TI - Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. AB - We have investigated the tissue distribution, toxicity, and antitumor activity of anthracyclines encapsulated in hydrogenated phosphatidylinositol (HPI)-containing liposomes which show a characteristic long circulation time in plasma (J. Natl. Cancer Inst., 81: 1484-1488, 1989). Phosphatidylglycerol (PG)-containing liposomes were used for comparison. Doxorubicin (DOX) or epirubicin (EPI) was encapsulated in the aqueous interior of small (65-100 nm mean diameter) HPI or PG liposomes. The DOX and EPI levels in i.m. tumor implants of the J6456 lymphoma were significantly raised by delivery in HPI liposomes but not by delivery in PG liposomes. No such increase was observed in normal muscle tissue. When DOX encapsulated in HPI liposomes was injected i.v. into BALB/c mice bearing an ascitic form of the J6456 lymphoma, more than 10% of the injected dose was recovered in the ascitic fluid in liposome-associated form. No significant accumulation of liposomal drug was observed in peritoneal washes from tumor-free mice. DOX encapsulation in either PG- or HPI-containing liposomes reduced the lethal toxicity of the drug in mice. However, only the HPI-DOX formulation was significantly more active than free DOX in the treatment of the ascitic J6456 tumor at all dose levels tested. Therapeutic results with EPI encapsulated in HPI liposomes also showed an efficacy superior to that of free EPI. These studies provide evidence that anthracyclines delivered in long-circulating liposomes extravasate with relative selectivity in tumor areas, improving the overall therapeutic index. PMID- 1737352 TI - Fludarabine infusion potentiates arabinosylcytosine metabolism in lymphocytes of patients with chronic lymphocytic leukemia. AB - Our previous work has shown that incubation of K562 cells or lymphocytes from patients with advanced chronic lymphocytic leukemia (CLL) with arabinosyl-2 fluoroadenine (F-ara-A) potentiates the rate of arabinosylcytosine 5' triphosphate (ara-CTP) synthesis during subsequent treatment with arabinosylcytosine (ara-C). To test the biochemical modulation of ara-CTP in a clinical setting, we designed a protocol to administer fludarabine (Fludara, F ara-AMP) and ara-C in a pharmacologically directed sequence for patients with CLL refractory to conventional fludarabine therapy. ara-C was infused in seven patients with progressive CLL at a dose rate that maximizes ara-CTP accumulation (0.5 g/m2 during 2 h). Fludarabine (30 mg/m2 during 30 min) was infused 20 h later, followed by a second, identical dose of ara-C at 24 h, when the concentration of F-ara-A 5'-triphosphate (F-ara-ATP) was maximal in CLL cells. Comparison of ara-CTP pharmacokinetics in circulating CLL cells demonstrated that the ara-CTP area under the curve increased by a median of 1.5-fold (range, 1.1- to 1.7-fold) after fludarabine infusion. Plasma pharmacokinetics indicated that neither the median steady-state ara-C concentrations nor the levels of its deamination product arabinosyluracil were significantly affected by fludarabine infusion. The median rate of ara-CTP elimination was slightly faster after fludarabine treatment (t1/2, 6.7 versus 5.8 h), suggesting that catabolism of ara CTP was not responsible for the increased ara-CTP area under the curve. The rate of ara-CTP accumulation by CLL cells after fludarabine infusion, however, was increased by a median of 1.3-fold in seven of the eight patients (range, 1.2- to 1.8-fold); the peak occurred within 1 h of the end of the infusion. In vitro incubation of leukemic lymphocytes with F-ara-A before ara-C also showed a median 1.3-fold increase in the rate of ara-CTP accumulation. Thus, infusion of fludarabine before ara-C augments ara-CTP metabolism in leukemic lymphocytes. This knowledge should be considered in the design of combination chemotherapy. PMID- 1737353 TI - Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmunoconjugates for imaging and therapy. AB - The development of stable immunoconjugates by the advent of macrocyclic metal chelating agents (DOTA) has enabled us to study the ability of 111In-DOTA-labeled monoclonal antibodies to detect tumor lesions in a pilot radioimmunolocalization study, as well as to evaluate the kinetics, toxicity, and efficacy of i.p. administered 90Y-DOTA-labeled murine monoclonal antibody in a Phase I/II clinical trial of advanced ovarian cancer. The development of serum sickness-like reactions in three of six treated patients, in the absence of previous monoclonal antibody administration, led us to study the potential immunogenicity of the new chelate. Six patients with ovarian cancer received 25 mg of HMFG1 monoclonal antibody coupled with 90Y-DOTA (doses of radioactivity, 15 to 25 mCi), administered i.p. Eight patients with various malignant tumors received low doses (220 micrograms to 1 mg) of monoclonal antibodies, labeled with 111In-DOTA, i.v. for imaging studies. Using a solid-phase enzyme-linked immunosorbent assay method, the immunogenicity of DOTA was evaluated. Serial dilutions of patients' sera, before and after imaging or therapy with DOTA-coupled monoclonal antibodies, as well as sera from patients who did not receive DOTA-coupled antibody, were screened on enzyme-linked immunosorbent assay plates coated with human serum albumin (HSA), HSA-2-iminothiolane, and HSA-2-iminothiolane-benzyl DOTA. All patients treated with i.p. monoclonal antibody developed anti-DOTA antibodies. Four of eight patients who received i.v. "imaging" doses of DOTA coupled monoclonal antibody developed antibodies against DOTA. The levels of anti DOTA response correlated with the amount of injected radioimmunoconjugate (r = 0.889, P less than 0.001). None of the patients who received DOTA-coupled antibody had detectable antibodies against the macrocycle before immunoconjugate administration. We then addressed further the restriction of the immune response against the macrocycle. We found that there was no or very low response against the aromatic ring attached to DOTA. Most, if not all, of the immune response is directed against the DOTA ring structure. Affinity purification of anti-DOTA antibody from serum enabled quantitation of these antibodies in the serum of patients. An inverse, statistically significant correlation was observed between the percentage of binding inhibition of a patient's serum to DOTA, by HSA-2 iminothiolane-DOTA (100 micrograms/ml) and the level of anti-DOTA immunoglobulin in the serum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1737354 TI - Circadian variation of tumor blood flow in rat subcutaneous tumors and its alteration by angiotensin II-induced hypertension. AB - Circadian fluctuation in tumor blood flow of the rat subcutaneous tumor was investigated. Tumor tissue blood flows in the daytime zone (10 a.m. to 4 p.m.) and in the nighttime zone (10 p.m. to 4 a.m.) in both the first phase (doubling time of tumor volume = 1.7 days) and the second phase (doubling time of tumor volume = 5.7 days) of growth of the LY80 tumor in rats were measured using the hydrogen gas clearance technique. In the first phase of tumor growth, the tumor blood flow was 20.3 +/- 12.2 ml/min/100 g in the daytime zone (n = 22) and 46.6 +/- 19.3 ml/min/100 g in the nighttime zone (n = 22). In the second phase, tumor blood flow was 9.6 +/- 5.7 ml/min/100 g in the daytime zone (n = 45) and 19.4 +/- 8.2 ml/min/100 g in the nighttime zone (n = 38). Tumor blood flow in the nighttime zone was significantly higher than that in the daytime zone (first phase, P less than 0.001; second phase, P less than 0.001). However, there were no significant differences in the mean arterial blood pressure, tumor size, and body weight of rats between the daytime zone and the nighttime zone. There was also a marked difference in the effect of angiotensin II-induced hypertension on tumor blood flow between the daytime zone and the nighttime zone. These results suggest that circadian fluctuations in tumor blood flow should be carefully considered when developing strategies to maximize the effectiveness of cancer therapy in relation to the flow rate of circulating blood. PMID- 1737355 TI - SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer. AB - The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer. PMID- 1737356 TI - Changes in microtubules, microtubule-associated proteins, and intermediate filaments during the differentiation of HL-60 leukemia cells. AB - The cytoskeleton is composed mainly of microtubules (MT), microfilaments, and intermediate filaments (IF) that form a structural network which connects cellular membranes, cytoplasmic organelles, and the nucleus. Since the cytoskeleton may be involved in modulating signal transduction and in the morphological and structural changes that occur during cellular proliferation and differentiation, cytoskeletal changes were measured by immunofluorescence microscopy and fluorescence-activated cell sorter analysis during the differentiation of HL-60 leukemia cells induced by retinoic acid (RA). Differentiated HL-60 cells exhibited increased staining intensity and altered organization of MT and IF, as visualized by immunofluorescence microscopy with anti-tubulin monoclonal antibody and anti-vimentin antibody, respectively. A new procedure was developed and used to measure the content of the cytoskeletal components of HL-60 cells during the process of maturation. HL-60 cells were fixed with formaldehyde in an MT-stabilizing buffer, permeabilized using L lysophosphatidylcholine, stained for immunofluorescent measurement with antibodies specific for particular cytoskeletal components, and analyzed by flow cytometry. Terminally differentiated cells produced by exposure to RA contained larger amounts of MT and the IF vimentin. During the course of the maturation process, a transient increase in the amounts of the microtubule-associated proteins, (MAPs) MAP2 and tau, occurred. An RA-supersensitive clone, designated HL-60/S4, and an RA-resistant clone, designated HL-60/R3, were developed by mutagenization and selection. Use of these clones supported the concept that the observed changes in MT, MAPs, and vimentin were associated with the differentiation process rather than being due to other effects produced by the retinoid. Thus, the findings suggest that changes in MT, MAPs, and IF are important to the terminal maturation of leukemia cells. PMID- 1737357 TI - Ploidy and specific karyotypic changes during promotion with phenobarbital, 2,5,2',5'-tetrachlorobiphenyl, and/or 3,4,3'4'-tetrachlorobiphenyl in rat liver. AB - Polychlorinated biphenyls are a group of industrial chemicals that are widely distributed in the environment. Since these compounds occur as mixtures, studies of their possible interactive effects are important. In order to determine whether an interaction of 2,5,2',5'-tetrachlorobiphenyl (TCB) with 3,4,3',4'-TCB occurs during multistage hepatocarcinogenesis in vivo, like that previously observed in lymphocytes in vitro (L. M. Sargent et al., Mutat. Res., 224: 79-88, 1989), we exposed rats to a single initiating dose of diethylnitrosamine (DEN), 10 mg/kg after a 70% partial hepatectomy, and subsequently to 0.1 ppm 3,4,3',4' TCB and/or 10 ppm 2,5,2',5'-TCB in the diet for 1 year. Administration of each of the TCBs alone after DEN initiation resulted in a low incidence of chromosomal damage in hepatocytes; but when the two were given together after DEN initiation, there was a more than additive effect on this parameter at both 7 and 12 months which was highly significant. Administration of the TCBs alone or in combination in the absence of DEN initiation also resulted in chromosomal damage, approaching that seen in livers of animals initiated with DEN when sacrificed at 12 months. In animals receiving 0.05% phenobarbital for a 12-month period after initiation with DEN, a significant degree of chromosomal breakage and fragment formation occurred both in hepatocytes expressing the ectoenzyme gamma glutamyltranspeptidase (GGT) and in those that were GGT negative. However, the GGT-negative cells showed a significantly lower incidence of chromosomal damage than the GGT-positive hepatocytes. Exposure to phenobarbital for 7 months after DEN initiation resulted in no significant chromosomal damage in hepatocytes, whether GGT positive or GGT negative. Some degree of specificity in chromosomal alterations was seen in hepatocytes of animals initiated with DEN and promoted either with a combination of TCBs or with phenobarbital. The most frequent alterations seen were a trisomy of chromosome 1 or of its long arm and a monosomy of chromosome 3 or its short arm. Some chromosome 7 aberrations were also seen. The highest frequency of specific aberrations occurred in hepatocytes from rats that also bore hepatocellular carcinomas, suggestive of the hypothesis that genes involved in the development of hepatic carcinoma may reside in chromosome 1 and/or 3 of the rat. PMID- 1737358 TI - Quantitative ultrastructural effects of cisplatin (Platinol), carboplatin (JM8), and iproplatin (JM9) on neurons of freshwater snail Lymnaea stagnalis. AB - Qualitative and quantitative ultrastructural effects of the platinum compounds cisplatin (Platinol), carboplatin (JM8), and iproplatin (JM9) were studied on two types of identified peptidergic neuron (caudodorsal cells, light green cells) in the pond snail Lymnaea stagnalis. Depending on the parameter under investigation, either one or both cell types were studied. Central nervous systems of the snail were incubated for 5 and 20 h in various identical and equitoxic drug concentrations. Cisplatin had the most severe effects. Platinol, i.e., cisplatin dissolved in NaCl solution with the addition of HCl (pH 2.0-3.0), as well as cisplatin dissolved in snail Ringer's solution (pH 7.8), caused swelling of axons and distensions of the intercellular spaces. This drug induced an increase in chromatin clump size in the caudodorsal cells (20-h incubation), while carboplatin and iproplatin induced the formation of many small chromatin clumps. Incubation in snail Ringer's solution (controls) and cisplatin affect the morphology of the nucleoli. At high dosages of cisplatin, the nucleoli of light green cells were transformed into homogeneous dense structures. The data indicate that platinum compounds react with nuclear and nucleolar DNA. All three drugs affected the activity and organization of the rough endoplasmic reticulum and the Golgi apparatus of the peptidergic neurons studied (qualitative observations). These effects, which point to a reduced neuropeptide synthesis, may be secondary, i.e., exerted via inhibition of RNA synthesis and ribosome formation (nucleoli). The fact that the number of neuropeptide granules in the cytoplasm of the cells remained constant (both cell types) may indicate that granule transport was also inhibited. Cisplatin and iproplatin induced an increase in the number of lysosomes in the light green cells. The number of lipid droplets in these cells was not affected by drug treatment. The results corroborate clinical data indicating that cisplatin is highly neurotoxic. Despite conflicting clinical data, observations on the snail neurons suggest that iproplatin is also neurotoxic, although less than cisplatin. Carboplatin is minimally neurotoxic, which is in accordance with clinical data. The central nervous system of Lymnaea is a suitable model for studying possible neurotoxic effects of platinum compounds. PMID- 1737359 TI - Quantitative mapping of 4'-iododeoxyrubicin in metastatic squamous cellcarcinoma by secondary ion mass spectrometry (SIMS) microscopy. AB - Secondary ion mass spectrometry microscopy enables quantitative mapping of chemical elements in tissue sections. It was used for the detection of 127I contained in 4'-iododeoxyrubicin (IDX). Metastatic cutaneous squamous cell carcinoma from 7 patients participating in a phase I study (IDX dose, 80 mg/m2, 10-min i.v. infusion) were biopsied 10 min after drug administration and compared to 3 controls who did not receive any treatment (one squamous cell carcinoma and 2 gastric carcinomas). Biopsy specimens were fixed and embedded in methacrylate resin. Then, serial semithin sections (3 microns) were analyzed simultaneously with ionic and optimal microscopes in order to identify the histological structures given by the 31P distribution in which 127I in IDX was mapped. The iodine signal was undetected in controls and found mainly in the nuclei of tumor cells of the treated patients. Its concentration, measured in at least 30 nuclei of each specimen, was undetectable in 8% of the nuclei and 91% of them were within 1 and 16 ng/mg. The mean concentration of each specimen ranged from 5 to 23 ng/mg. This study demonstrates the capacity of ion microscopy to localize a cytotoxic drug (IDX) in a human biopsy specimen without the need for radioactive labeling and enables the evaluation of drug penetration in cancer cells which is critical for its activity. PMID- 1737360 TI - Chemically induced forestomach papillomas in transgenic mice carry mutant human c Ha-ras transgenes. AB - Forestomach papillomas and skin papillomas were induced very efficiently by a single dose administration of the chemical carcinogen methylnitrosourea (MNU) in transgenic mice (rasH2 line) carrying human hybrid c-Ha-ras genes, which encode the prototype p21 gene product. The incidence of forestomach papillomas was dose dependent; when 50 mg/kg of MNU were administered i.p., all of the transgenic mice (56 of 56) developed forestomach papillomas within 12 weeks after administration, whereas 5 and 0.5 mg/kg of MNU induced papillomas in 2 of 19 and 1 of 19 mice, respectively. Nine of 56 transgenic mice (16%) also developed skin papillomas at sites wounded by bites or scratches. Only 1 of 77 nontransgenic littermates developed forestomach papillomas after administration of 50 mg/kg of MNU, and no skin papillomas appeared within 12 weeks after MNU administration. The transgenes (integrated copy number, 5-6) in the tumors developed in 55 of 56 affected transgenic mice (98%) contained at least 1 copy of the transgene that was activated by somatic point mutation at the 12th codon, from GGC (Gly) to GAC (Asp). Because somatic point mutations at the 12th or 61st codon of transgenes have never been detected in normal tissues of transgenic mice thus far examined, these mutational activations of transgenes are tumor-specific events. RNA expression of these activated transgenes was also detected. From these results, it is suggested that somatic mutational activation of the human c-Ha-ras transgene plays a causative role in the occurrence of forestomach and skin papillomas induced by MNU administration in these transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress papillomagenesis. PMID- 1737361 TI - Control of Ha-ras-mediated mammalian cell transformation by Escherichia coli regulatory elements. AB - Inducible eukaryotic promoters, particularly those responsive to glucocorticoids or heavy metals, have been extensively used to study the consequences of induction of a target gene in mammalian cells. An alternative approach, intended to improve the selectivity of gene induction and to minimize perturbation of chromatin structure, is to utilize elements from prokaryotic regulatory systems that are unlikely to be shared by mammalian cells. We and others previously have shown that the lac repressor can function in mammalian cells and repress expression of a reporter gene controlled by a eukaryotic promoter containing a lac operator sequence. The reporter gene can be specifically activated by administration of the lactose analogue isopropyl beta-D-thiogalactoside. The target genes tested so far encode the biochemical and histochemical markers, chloramphenicol acetyltransferase and beta-galactosidase. As a model system to establish whether or not the lactose regulatory system can also be used to effectively modulate a cellular phenotype, NIH 3T3 cells were made transgenic for a constitutively expressed lacI gene, encoding lac repressor, and an activated human Ha-ras gene directed by a simian virus 40 promoter within which a lac operator sequence had been embedded. In the absence of inducer, cells were phenotypically untransformed. Consequent to isopropyl beta-D-thiogalactoside administration, four biological end points characteristic of a transformed phenotype were observed. Consistent with transformation, the cells assumed an altered morphology; they displayed a reduced density inhibition of growth; they acquired the capacity to grow in soft agar; and they were released from a G0 block following serum deprivation. The data demonstrate that regulation of gene expression in mammalian cells by the lactose regulatory system affords a sensitive means for modulating cellular phenotype. PMID- 1737362 TI - Aflatoxin-transformed C3H/10T1/2 cells overexpress protein kinase C and have an altered response to phorbol ester treatments. AB - The aflatoxin B1-transformed C3H/10T1/2 (10T1/2) cell line 7SA has disordered growth in culture and is tumorigenic in syngeneic mice. Chronic exposure (14 days) of 10T1/2 and 7SA cells to phorbol 12,13-dibutyrate (PDBu) increased the saturation density of 10T1/2 cells but dramatically slowed the entry of 7SA cells into the log phase of growth without affecting their final saturation density. Similar PDBu treatment of low-density cultures dramatically decreased the size of 7SA colonies. Both cell lines bound [3H]PDBu in a specific and saturable manner. Analysis of this binding yielded linear Scatchard plots for both cell lines with distinctly different Kd values (10.7 nM for 10T1/2 versus 54.5 nM for 7SA). The total amount of [3H]PDBu bound was 2-fold greater in the 7SA cells versus the 10T1/2 cell line. Both cell lines released arachidonic acid following a 2-h exposure to PDBu; however, the magnitude of the response of the 7SA cells was only one-half that of the 10T1/2 cells. Western blot analysis of protein kinase C (PKC) using specific anti-PKC antibodies revealed a greater total amount of PKC alpha in the 7SA cells relative to an equal number of 10T1/2 cells. No immunoreactive PKC alpha was found in either cell line 16 h after exposure to 600 nM PDBu; however, PKC alpha returned to control levels in both cell lines 24 h after removal of the phorbol ester. These results suggest that an overexpression of PKC alpha may play a role in the altered biological properties of aflatoxin transformed 10T1/2 cells. PMID- 1737363 TI - Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis. AB - Apoptosis is a form of cell death in which the cell "participates," such that metabolic energy and often protein synthesis are required for the death to occur. Once begun, the process of apoptosis proceeds in an ordered fashion. In the earliest phase DNA fragmentation occurs, accompanied by cell shrinkage and dilation of the endoplasmic reticulum. This is followed by cell fragmentation with the formation of sealed membrane vesicles, termed apoptotic bodies. In the present study we have demonstrated that the fungal metabolite cytochalasin B inhibits cell fragmentation and the formation of apoptotic bodies, probably by its ability to interfere with actin polymerization. This effect was seen when HL 60 cells were pretreated with cytochalasin B and then exposed to one of a number of apoptosis-inducing agents, including UV irradiation, camptothecin, aphidocholin, or PMA plus ionomycin. The observed effect was not peculiar to HL 60 cells, inasmuch as it was also seen for both Molt-4 and U-937 cell lines. Cytochalasin B had no effect on DNA fragmentation occurring in the earliest stage of apoptosis, and it appeared to have no inhibitory effects on nuclear fragmentation. Staurosporin had an effect similar to that seen with cytochalasin B, probably due to its ability to inhibit protein kinase C, which is a known potentiator of microfilament assembly. These data demonstrate that microfilament assembly is necessary for the formation of apoptotic bodies in the later stages of the apoptotic process. PMID- 1737364 TI - Mechanism of interferon action in hairy cell leukemia: a model of effective cancer biotherapy. AB - Hairy cell leukemia (HCL) is one of the few malignancies for which alpha interferon (IFN alpha) is considered effective first-line therapy. However, the mechanisms of action of this agent in vivo have been the subject of much debate; in particular, the issue of whether clinical improvement in IFN-alpha-treated HCL patients is dependent upon enhancement of host defenses or upon direct actions of IFN alpha upon the hairy cell remains unresolved. In this review, we examine the evidence supporting both lines of argument and synthesize this information within the framework of clinical studies of IFN alpha in HCL, the purpose being to determine which proposed mechanisms of IFN alpha action are indeed effective in vivo. From our analysis, it appears that the beneficial effects of IFN alpha upon immune function are important in decreasing the frequency of infectious complications of HCL but that these effects are probably not responsible for hairy cell elimination and cannot therefore account for major responses to IFN alpha therapy. We conclude that the primary mechanism of action of IFN alpha in HCL involves the induction of hairy cell differentiation towards a stage less responsive to growth factor stimulation, the primary consequence being proliferative inhibition. These effects may mimic events that occur during normal lymphocyte development, suggesting that the benefits of biotherapeutic agents might best be harnessed via studies of the effects of multiple and sequential biological response modifiers upon the growth and differentiation patterns of normal and malignant cells. Hairy cell leukemia could thus serve as an excellent model in which to investigate combined cancer biotherapy; the implications of our present understanding of IFN alpha in HCL to the biotherapy of cancer are discussed. PMID- 1737365 TI - Cooperative estrogen receptor interaction with consensus or variant estrogen responsive elements in vitro. AB - Specific binding of estradiol-liganded, partially purified calf uterine estrogen receptor (ER) to a 38-base pair estrogen responsive element (ERE) consensus sequence, containing the inverted repeat 5'-GGTCAnnnTGACC-3', was measured in vitro. The ERE sites were inserted as single or multiple tandem copies in a plasmid vector [p GEM-7Zf(+)]. Results showed that one dimeric ER can interact with one ERE, and steric constraints do not inhibit binding of ER to adjacent EREs. Molybdate-stabilized monomeric (4S) ER did not bind to EREs. ER bound to single and tandem double EREs with Kd values of 0.24 and 0.23 nM, respectively. When the plasmid contained three or more tandem copies of the ERE, ER bound in a cooperative manner, as indicated by convex Scatchard plots and Hill coefficients greater than 1.5. To determine those characteristics of the consensus sequence that are important for maximal high-affinity ER binding, ten variant ERE oligomer sequences were synthesized and cloned into pGEM-7Zf(+) as single copies or as four copies in tandem. ER binding affinity was maximal for the consensus ERE and was reduced for variants containing one or two nucleotide changes in the inverted repeat. The number of nucleotides separating the inverted repeat in the ERE was critical for high-affinity ER binding. Certain sequence-variant EREs when cloned as single copies bound less ER compared to the consensus ERE, yet when cloned as four tandem copies, ER binding displayed cooperativity by Scatchard and Hill analyses. Results demonstrate that cooperative interactions noted in vivo by others are present when measured in vitro. Results strongly imply that the number, spacing, and nucleotide sequence of EREs could precisely control the amount of ER binding to estrogen-responsive genes. PMID- 1737366 TI - Interferon-stimulated genes in interferon-sensitive and -resistant chronic myelogenous leukemia patients. AB - alpha-Interferon induces hematological and cytogenetic remissions in some individuals with newly diagnosed Philadelphia-positive chronic myelogenous leukemia. However, interferon-resistant disease occurs in a consistent patient subset (primary resistance) and develops during therapy in additional patients (secondary resistance). Several alpha-interferon-inducible genes have been characterized. In interferon-resistant cell line variants, defects in these genes have been implicated in the mechanisms mediating resistance. We have, therefore, evaluated mRNA expression of four interferon-stimulated genes (ISGs) following alpha-interferon therapy. Twenty-seven chronic myelogenous leukemia patients (ten interferon-sensitive patients, 17 interferon-resistant patients) were studied. Peripheral blood samples were collected prior to and 1 to 7 days after starting interferon therapy and analyzed for the expression of 2'-5' oligoadenylate synthetase, ISG-15, ISG-54, and 6-16 transcripts. Following therapy with alpha interferon, 2'-5' oligoadenylate synthetase, ISG-54, and 6-16 transcripts were discerned in all patients regardless of their response to interferon. The ISG-15 message was detected in eight of nine interferon-sensitive and in 15 of 16 interferon-resistant patients, as well. Overall, no consistent defect in the ISG system could be identified. Therefore, lack of induction of these genes cannot explain resistance to alpha-interferon in chronic myelogenous leukemia patients. Other mechanisms such as posttranslational modification, leading to defects in the ISG corresponding proteins, may play a role in the development of resistance. PMID- 1737367 TI - Influence of intracellular glutathione on selenite-mediated growth inhibition of canine mammary tumor cells. AB - The present studies demonstrate that the ability of supplemental selenite to alter the in vitro growth of canine mammary tumor cell line 13 was dependent on the quantity and duration of selenium exposure and on the culture density. Exposure to 3.2 microM selenite did not significantly alter growth but led to an increase in intracellular glutathione (GSH). The severity of growth inhibition between 3.2 and 9.6 microM selenite was dependent on the duration of exposure and culture density. The toxicity of selenite generally increased as the culture density increased. Likewise, changes in intracellular GSH were dependent on the quantity and duration of selenite exposure and the culture density. Depressing intracellular GSH by increasing the culture density or by incubating with buthionine sulfoximine; a specific inhibitor of gamma-glutamyl cysteine synthetase, increased the severity of growth inhibition caused by selenite and markedly increased cellular retention of selenium. Nevertheless, marked cellular retention of selenium did not occur until growth was inhibited by more than 50%. The present studies revealed that the log of the molar ratio of GSH to selenium correlated negatively with the severity of growth inhibition (P less than 0.0001). These studies suggest that cellular toxicity of selenite is dependent on the regulation of the GSH:selenium ratio. An inability to regulate this ratio likely leads to the accumulation of toxic seleno compounds. PMID- 1737368 TI - No change in repair capacity of mouse lung irradiated three months after a single dose of cyclophosphamide. AB - The repair capacity of mouse lung was determined at 3 months after a single i.p. injection of cyclophosphamide (Cy) at a maximally tolerated dose of 275 mg/kg. Mice were irradiated to the whole thorax only with 1, 2, 9, or 15 fractions of X rays using doses/fraction ranging from 1.2 to 11 Gy. Breathing rate (breaths per minute), histology and pulmonary mortality were used to assess lung damage. Raw breathing rate data were converted to quantal response data by scoring the number of mice in each dose group in each fractionation schedule with a breathing rate 1.3 times the breathing rate of control mice. Dose-response curves of mortality and the converted breathing rate data were constructed at 15 weeks after irradiation (approximately 28 weeks after drug treatment) fitted by logit analysis and 50% effective doses with 95% confidence limits obtained. Values of alpha/beta were obtained by using the direct analysis method of H. D. Thames et al. (Int. J. Radiat. Biol., 49:999-1009, 1986). The alpha/beta for mice given Cy 3 months before radiation was 3.69 Gy (95% confidence limits, 2.83, 4.69 Gy) and 3.06 Gy (95% confidence limits, 2.31, 3.99 Gy) for the lethality data and breathing rate data, respectively. These alpha/beta values are in good agreement with the previously published ranges of alpha/beta of 3 to 4 Gy for mouse lung not given Cy previously. Because the repair capacity of the target cells of a tissue govern the fractionation response and choice of fractionation regimen in clinical radiotherapy, these data indicate that the fractionation regimen used can remain the same as that used in non-drug-treated lungs when the lung is irradiated 3 months after exposure to Cy. PMID- 1737369 TI - Cellular mechanisms associated with the lack of chronic thermotolerance expression in HeLa S3 cells. AB - Chronic thermotolerance is an operational definition for that resistance to cell killing by heat which develops during a protracted exposure at temperatures generally in the range of 41.5-42.5 degrees C which is usually observed as a reduction in the slope of the survival curve. While Chinese hamster ovary (CHO) cells are generally more sensitive to high-temperature heat shock than HeLa cells, studies of cells maintained in suspension culture at 41.5 degrees C demonstrated CHO cells to be more resistant to cell killing at this temperature than HeLa cells, due to the expression of chronic thermotolerance in the hamster cell line and the corresponding lack of chronic thermotolerance expression in the HeLa cell line. Experiments were conducted in the two cell lines while heating under identical conditions, in order to detect any cell line-specific changes in heat-induced perturbation of cell cycle progression and the expression of chronic thermotolerance. Our results showed that CHO cells exhibited a G1 block which lasted throughout the course of the 32-h heating period. HeLa cells, however, failed to accumulate in G1, progressing instead into S phase where spontaneous premature chromosome condensation and nuclear fragmentation were observed. This accumulation of cells with condensed chromatin possessing S-phase DNA content exhibited a linear, one-to-one functional relationship with the fraction of dead cells. Previous studies (M.A. Mackey and W.C. Dewey, Int. J. Hyperthermia, 5:405 415, 1989) demonstrated that synchronized S-phase CHO cells heated at 41.5 degrees C and 42 degrees C were unable to express chronic thermotolerance. Therefore, we hypothesize that progression of cells out of G1 phase into S and G2 M phases leads to lethal processes that prevent the expression of chronic thermotolerance in the HeLa cell line. This hypothesis is strengthened by the observed correlation between the accumulation of "mitotic-like" cells and decreased survival, suggesting that the G1 block observed in CHO cells is causally connected with the expression of chronic thermotolerance. PMID- 1737370 TI - c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. AB - Amplification of the c-myc and HER2/neu genes was found in 20 and 23%, respectively, of primary breast cancer tissues derived from 282 patients (median follow-up, 74 months). c-myc amplification was observed more frequently in larger tumors (P = 0.01) and in lymph node-positive patients (P = 0.01) but was not associated with age, menopausal status, or with differentiation grade or steroid receptor status. c-myc amplification was strongly negatively correlated with HER2/neu amplification (P less than 0.001). In univariate analysis, amplification of c-myc proved to be a significant predictor of reduced relapse-free and overall survival (for both, P less than 0.001). In multivariate analysis for relapse-free survival, c-myc amplification significantly (P = 0.001) added to the prognostic power of tumor size (P less than 0.001), lymph node status (P less than 0.001), and estrogen receptor status (P = 0.003), with the highest relative failure rate (1.8) after lymph node status (2.2). In this pilot study, c-myc amplification was predictive for outcome, especially among patients with node-negative disease or steroid receptor-positive tumors; 51 and 46% differences in actuarial 5-year recurrence rates when compared to patients with tumors with normal c-myc gene copy numbers, respectively. HER2/neu amplification was not associated with relapse-free survival but weakly with shorter overall survival in univariate analysis (P = 0.035). Only in the relatively small subgroup of steroid receptor negative tumors, HER2/neu amplification may identify those patients with an increased risk of death. In conclusion, amplification of c-myc is an independent powerful prognosticator, particularly in node-negative and steroid receptor positive breast cancer, whereas HER2/neu amplification may be of limited prognostic value, only in steroid receptor-negative disease. PMID- 1737371 TI - Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein). AB - Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone. PMID- 1737372 TI - Human lymphoblastoid cells with acquired resistance to C2-desamino-C2-methyl-N10 propargyl-5,8-dideazafolic acid: a novel folate-based thymidylate synthase inhibitor. AB - We describe the characterization of human lymphoblastoid cell lines with acquired resistance (greater than 20,000-fold) to a novel folate-based thymidylate synthase (TS) (EC 2.1.1.45) inhibitor, C2-desamino-C2-methyl-N10-propargyl-5,8 dideazafolic acid (ICI198583). This acquired resistance was associated with a 64 fold amplification of the TS gene, a similar elevation in the corresponding mRNA, and an approximately 200-fold increase in both TS activity and TS protein. This amplification was maintained when the cells were grown in the absence of the selective agent, ICI198583, for 340 generations. TS isolated from one of the resistant cell lines, W1-L2:C1, displayed inhibition kinetic parameters similar to those of TS isolated from the parent W1-L2 cell line. It thus appears unlikely that resistance is due to an altered TS enzyme having a lower affinity for ICI198583. The resistant cell line, W1-L2:C1, was cross-resistant to other folate based TS inhibitors but was as sensitive as the parent cell line, W1-L2, to 5 fluorodeoxyuridine. The W1-L2:C1 cell line was collaterally sensitive to the classical dihydrofolate reductase (EC 1.5.1.3) inhibitor methotrexate as well as to the lipophilic dihydrofolate reductase inhibitors metoprine and 2,4-diamino-5 methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazolin e glucuronic acid salt (also called trimetrexate). When the W1-L2 and W1-L2:C1 cell lines were exposed to 1 microM ICI198583 for 24 h they accumulated the same concentration of total cellular ICI198583 polyglutamates despite the fact that the latter cell line accumulated a 300-fold greater concentration of ICI198583 monoglutamate. As polyglutamates, the tetra- and pentaglutamate forms predominated in the W1-L2 cell line, whereas the diglutamate form predominated in the W1-L2:C1 cell line, with few higher polyglutamates being detected. The lack of tri- and higher polyglutamates of ICI198583 (i.e., the more active species) in the W1-L2:C1 cell line may also contribute to the observed resistance. These findings may have important implications in light of the rapid onset of resistance to antifolates in the clinic. PMID- 1737373 TI - Expression of O6-methylguanine-DNA methyltransferase in six human medulloblastoma cell lines. AB - Six well characterized human medulloblastoma cell lines (D283 Med, Daoy, D341 Med, D384 Med, D425 Med, and D458 Med) were examined for the expression of O6 methylguanine-DNA methyltransferase (MGMT) by activity and Western and Northern blot analysis. High levels of MGMT activity were present in D283 Med, Daoy, D341 Med, and D384 Med (1.36, 0.80, 1.68, and 1.62 pmol/mg of protein, respectively), but negligible MGMT activity was detected in D425 Med and D458 Med (0.06 and 0.05 pmol/mg of protein, respectively), which were derived separately at different times from the same patient. The presence of MGMT protein and its transcript was demonstrated in D283 Med, Daoy, D341 Med, and D384 Med, but both the protein and the mRNA were undetectable in D425 Med and D458 Med. Nevertheless, all six cell lines contained an apparently unaltered MGMT gene, as determined by Southern blot analysis. The absence of MGMT activity in D425 Med and D458 Med is likely due to the absence of the protein, resulting from a lack of transcription of the MGMT gene. The varying levels of expression of MGMT in medulloblastoma cells found in this study should provide a molecular basis for drug design and selection in chemotherapy of this tumor. PMID- 1737374 TI - Biotransformation in carcinogen-induced diploid and polyploid hepatocytes separated by centrifugal elutriation. AB - Biotransformation in carcinogen-induced diploid and polyploid hepatocytes was studied using isozyme-selective substrates for several enzyme pathways. Diploid hepatocytes were induced by partial hepatectomy, a single injection of diethylnitrosamine, and 4 weeks of 2-acetylaminofluorene (2-AAF) feeding. Then, after an additional 3-5 weeks on the control diet, diploid and polyploid hepatocytes were separated from freshly isolated hepatocytes by centrifugal elutriation. Benzo(a)pyrene hydroxylase, ethoxyresorufin O-deethylase, and methoxycoumarin O-demethylase activities were approximately 15-40% lower in the diploid hepatocyte fraction than in the polyploid cell fraction. Activities of 1 chloro-2,4-dinitrobenzene, glutathione S-transferase, 3-hydroxy-benzo(a)pyrene or 4-hydroxybiphenyl UDP-glucuronosyltransferase, and DT-diaphorase were not different in the two cell fractions. Determination of activity during the 2-AAF treatment indicated that 2-AAF increased 7-ethoxyresorufin O-deethylase and 3 hydroxybenzo(a)pyrene glucuronosyltransferase activities by 300 and 200%, respectively, in both the diploid and polyploid hepatocyte fractions. Administration of phenobarbital for 4 days at the end of the control diet period increased ethoxyresorufin and methoxycoumarin dealkylations by 2- and 4-fold, and 3-hydroxybenzo(a)pyrene glucuronidation and 1-chloro-2,4-dinitrobenzene conjugation with glutathione by 1.5- to 2-fold in both hepatocyte fractions. Slight increases in benzo(a)pyrene hydroxylation and 4-hydroxybiphenyl glucuronidation were also evident in diploid cells. Although there is a slight decrease in cytochrome P-450-dependent monooxygenase activities, these data indicate that carcinogen-induced diploid hepatocytes do not show the typical toxicant-resistant phenotype observed in preneoplastic hepatocytes of altered liver foci, which are characterized by large decreases in monooxygenase biotransformations as well as increased activities of several phase II enzymes. This finding is compatible with the hypothesis that 2-AAF-induced nonploidizing growth of diploid hepatocytes is caused by nontoxic mechanisms in the present experimental paradigm. In addition, carcinogen-induced diploid cells respond to phenobarbital in a manner similar to that of polyploid hepatocytes. PMID- 1737375 TI - Inhibitory effect of green tea in the drinking water on tumorigenesis by ultraviolet light and 12-O-tetradecanoylphorbol-13-acetate in the skin of SKH-1 mice. AB - Green tea was prepared by extracting 12.5 g of green tea leaves twice with 500 ml of boiling water, and the extracts were combined. This 1.25% green tea extract (1.25 g of tea leaves/100 ml of water) contained 4.69 mg of green tea extract solids per ml and was similar in composition to some green tea beverages consumed by humans. A 2.5% green tea extract (2.5 g of tea leaves/100 ml of water) was prepared similarly. Treatment of female SKH-1 mice with 180 mJ/cm2 of ultraviolet B light (UVB) once daily for 7 days resulted in red sunburn lesions of the skin. The intensity of red color and area of these lesions were inhibited in a dose dependent fashion by the administration of 1.25 or 2.5% green tea extract as the sole source of drinking water before and during UVB treatment. Treatment of female SKH-1 mice with 180 mJ/cm2 of UVB once daily for 10 days followed 1 wk later by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 25 wk resulted in the development of skin tumors. The formation of skin tumors was inhibited by administration of 1.25% green tea extract as the sole source of drinking water prior to and during the 10 days of UVB treatment and for 1 wk after UVB treatment. In additional experiments, female SKH-1 mice were treated with 200 nmol of 7,12-dimethylbenz(a)anthracene followed 3 wk later by irradiation with 180, 60, or 30 mJ/cm2 of UVB twice weekly for 30 wk. UVB-induced formation of skin tumors and increased spleen size were inhibited by administration of 1.25% green tea extract as the sole source of drinking water prior to and during the 30 wk of UVB treatment. In these experiments, treatment of the animals with the green tea extract not only decreased the number of skin tumors but also decreased substantially the size of the tumors. In additional studies, SKH-1 mice were initiated by topical application of 200 nmol of 7,12 dimethylbenz(a)anthracene followed by twice weekly application of 12-O tetradecanoylphorbol-13-acetate for 25 wk. Administration of 1.25% green tea extract as the sole source of drinking water during promotion with 12-O tetradecanoylphorbol-13-acetate reduced the number and incidence of skin tumors. PMID- 1737376 TI - Effect of O6-benzylguanine on the sensitivity of human tumor xenografts to 1,3 bis(2-chloroethyl)-1-nitrosourea and on DNA interstrand cross-link formation. AB - We have previously shown that O6-benzylguanine can be used to deplete cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase and to enhance the sensitivity of human glioma (SF767) and colon tumor (HT29) cells to the cytotoxic effects of alkylnitrosoureas. In the present study, the combination of O6 benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was evaluated in vitro to determine the number of DNA interstrand cross-links formed and in vivo to compare the therapeutic index with that of BCNU alone. The number of DNA interstrand cross-links, as measured by alkaline elution, was increased in HT29 cells treated with 10 microM O6-benzylguanine for 2 h prior to BCNU exposure compared to cells treated with BCNU only. The number of single strand breaks was not increased by prior exposure to O6-benzylguanine. To evaluate the therapeutic index, HT29 and SF767 cells were grown as xenografts in nude mice and the tumor growth rate after treatment with BCNU alone was compared with the rate after treatment with O6-benzylguanine and BCNU. Treatment was administered i.p. when tumors reached 100-200 mm3. For animals bearing HT29 xenografts that were treated with 60 mg/kg O6-benzylguanine 1 h prior to 20 mg/kg BCNU, the average time for tumor volume to increase by 200% was 25 days, compared to 10 days for animals treated with 20 mg/kg BCNU alone. For animals bearing SF767 xenografts, the tumor growth of controls was not significantly different from that of animals treated with O6-benzylguanine alone or BCNU alone up to the maximally tolerated dose (50 mg/kg). For these 3 groups, the average time for tumors to reach 300 mm3 was 9-12 days. However, when animals were treated with 80 mg/kg O6-benzylguanine 1 h prior to receiving 20 mg/kg BCNU tumor size did not increase for at least 21 days. Our studies demonstrate that the therapeutic index of BCNU can be increased when given in combination with O6-benzylguanine. PMID- 1737377 TI - Metabolism and DNA binding of 2-nitropyrene in the rat. AB - 2-Nitropyrene (2-NP), a contaminant of ambient air, is a potent bacterial mutagen in the Ames assay and induces leukemia/lymphoma in female Sprague-Dawley rats. To understand the mechanistic basis for its tumorigenic activity, it is essential to elucidate the metabolic pathways of 2-NP in vivo. Such knowledge will also assist in developing analytical methods for monitoring human exposure to nitropolynuclear aromatic hydrocarbons in ambient air. Thus, 2-nitro[U-4,5,9,10 14C]pyrene was synthesized and administered to male F344 rats by intragastric gavage at a dose of 30 mg (0.4 mCi/mM)/kg body weight. During the first 48 h, 57.5% of the dose was eliminated in the feces and 9.7% was eliminated in the urine. Correspondingly, after 168 h, 58.9 and 10.6% were excreted in feces and urine, respectively. Fecal metabolites (isolated amounts) included 6-hydroxy-2 acetylaminopyrene (19.5%), 6-hydroxy-2-aminopyrene (10.4%), 2-aminopyrene (10.0%), 2-acetylaminopyrene (0.8%), and unmetabolized 2-nitropyrene (10.0%). 6 Hydroxy-2-acetylaminopyrene, 6-hydroxy-2-aminopyrene, and 2-aminopyrene were identified as their acetyl derivatives by comparison of their chromatographic retention times, mass spectra, and UV spectra to those of synthetic standards. Urinary metabolites included 6-hydroxy-2-acetylaminopyrene (2.0%); glucuronide conjugates were tentatively identified (3.2%). The results of this study indicate that nitroreduction and ring oxidation are metabolic pathways in vivo. For DNA binding studies, rats were treated with 2-nitro[4,5,9,10-3H]pyrene [1.6 mg (598 mCi/mM)/kg body weight]. The levels of binding (pM bound/mg DNA) were as follows: 1.3, liver; 1.14, mammary tissue; 0.65, lung; 1.67, kidney; and 1.8, bladder. Upon high-performance liquid chromatographic analysis of the DNA hydrolysate (liver, mammary, and kidney), approximately 2.0% of the radioactivity coeluted with the synthetic markers derived from nitroreduction, N-(deoxyguanosin-8-yl)-2 aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene. Thus, simple nitroreduction of 2-NP does not significantly contribute to the total DNA binding of 2-NP metabolites in vivo. The significance of each pathway for the tumorigenic effects of 2-NP remains to be examined. PMID- 1737378 TI - Growth-inhibitory action of an estrogen-chlorambucil conjugate (KM2210) in human breast cancer cell line MCF-7: its relation to reduction of estrogen receptor and transforming growth factor-alpha secretion. AB - We investigated the effects of a benzoate of an estradiol-chlorambucil conjugate (KM2210) and chlorambucil on growth, estrogen receptor, and secretion of transforming growth factor (TGF)-alpha in the hormone-dependent human breast cancer cell line MCF-7. In the presence of 10(-10)-10(-6) M KM2210, the estrogen induced growth of MCF-7 was completely inhibited. Inhibited growth of MCF-7 treated with 10(-8) or 10(-6) M KM2210 for 4 days was not rescued by removal of the drug and the addition of estradiol. By treatment of MCF-7 with KM2210 for 4 days, estrogen receptor-binding sites were decreased at 10(-8) M and were not detected at 10(-6) M but were unaltered by 10(-8) M chlorambucil. Moreover, estrogen receptor immunoreactivity and the level of estrogen receptor mRNA were decreased through treatment with 10(-6) M KM2210 for 4 days. These suppressions occurred prior to the onset of inhibitory action on MCF-7 growth. Secretion of TGF-alpha from MCF-7 was decreased by 4 days of treatment with 10(-8) and 10(-6) M KM2210 but not with chlorambucil. The addition of exogenous TGF-alpha generally restored the growth of MCF-7 treated with 10(-8) M KM2210. We concluded that KM2210 has irreversible or at least long-standing inhibitory effect on estrogen dependent growth of MCF-7. It is conceivable that the decrease of estrogen receptor renders the cell unable to respond to estrogen with increased TGF-alpha secretion and succeeding cell growth. PMID- 1737379 TI - Inhibition of experimental metastasis and cell adhesion of B16F1 melanoma cells by inhibitors of protein kinase C. AB - Phorbol esters which activate protein kinase C (PKC) have been shown to enhance experimental lung metastasis. Therefore, it was reasoned that inhibitors of PKC might also modulate metastasis. We have investigated this possibility using a PKC inhibitor, MDL 27,032 [4-propyl-5(4-pyridinyl)-2(3H)-oxazolone], as well as staurosporine and H-7. Treatment of B16F1 murine melanoma cells with MDL 27,032 for 24 h in culture and subsequent i.v. injection of the cells into mice resulted in greater than 90% inhibition of lung metastasis. Inhibition of metastasis was time dependent, with 90% of maximum inhibition occurring by 8 h of incubation. The 50% inhibitory concentration (IC50) for inhibition of metastasis with MDL 27,032 was 7 microM, a value similar to that for the inhibition of B16F1 membrane associated PKC (IC50 = 13 microM) but not cytosolic PKC (IC50 = 54 microM). B16F1 cells treated with MDL 27,032 for 24 h were less adherent than untreated cells to extracellular matrix/basement membrane proteins. Adhesion to fibrinogen and collagen IV was inhibited (IC50 = 6 microM and 48 microM, respectively) by MDL 27,032, whereas adherence to laminin and fibronectin was not affected, indicating that the drug affects specific adhesion molecules. MDL 27,032-treated cells were also found to be less adherent than untreated cells to human umbilical vein endothelial cells. The phosphorylation of an 80-kDa B16F1 cell plasma membrane protein was stimulated under conditions known to stimulate PKC activity, and MDL 27,032 inhibited this phosphorylation in a dose-dependent manner. MDL 27,032 was more potent than H-7 for the inhibition of metastasis but was significantly less potent than staurosporine. These results support the hypothesis that there is a critical role for PKC-mediated phosphorylation of cell surface adhesion receptors in metastasis. PMID- 1737380 TI - Beta 2-microglobulin gene is mutated in a human colon cancer cell line (HCT) deficient in the expression of HLA class I antigens on the cell surface. AB - The human colon cancer cell line HCT does not express any detectable HLA class I antigens on the cell surface. RNA blot analyses showed that HCT cells synthesize easily detectable levels of heavy chains as well as beta 2-microglobulin (beta 2m) transcripts. Experiments of immunoprecipitation revealed the presence of intracellular HLA heavy chains and the absence of beta 2m molecules. Sequencing studies, performed on polymerase chain reaction-mediated amplification of beta 2m specific complementary DNAs, indicated that in HCT cells both beta 2m genes are mutated. The first mutation consists of an 11-base deletion, corresponding to the first 11 base pairs of the second exon of the beta 2m gene. This mutation alters the reading frame, starting from the third amino acid residue of the mature beta 2m protein, resulting in the synthesis of a 31-amino acid peptide with no remarkable homology to any of the sequences stored in the protein database. The second mutation is a point mutation (C----A), resulting in a UAA stop codon corresponding to the 10th amino acid residue of the mature beta 2m. Therefore, it would appear that in HCT cells the beta 2m genes have undergone two different mutational changes. This is the first molecular demonstration of beta 2m mutations in a human epithelial cell line. PMID- 1737381 TI - CA54/61 as a marker for epithelial ovarian cancer. AB - Using a new one-step, double-determinant enzyme immunoassay, we performed quantitative measurements of a mucin-type glycoprotein antigen (CA54/61) that we recently detected in sera of ovarian carcinoma patients. When the cutoff value was set at 12 units/ml, at which a high diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD of healthy females)], the positive rates of ovarian serous, mucinous, clear cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous cystadenocarcinoma, more than one-half of the cases were positive, indicating the potential utility of the assay in the diagnosis of mucinous tumors. In sera from patients with benign ovarian tumors, only 9% (or 4%) of the cases were positive, indicating the quite high specificity of this test for ovarian carcinomas. To make a comparison between CA54/61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which value a high diagnostic efficiency was demonstrated [or at 35 units/ml (mean + 3 SD of healthy females)]. When both CA54/61 and CA125 were assessed in sera from 36 patients with mucinous cystadenocarcinoma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors. PMID- 1737382 TI - Altered gene expression of c-myc, epidermal growth factor receptor, transforming growth factor-alpha, and c-erb-B2 in an immortalized human breast epithelial cell line, HMT-3522, is associated with decreased growth factor requirements. AB - Activation of protooncogenes and constitutive secretion of autocrine growth factors are thought to be involved in the uncontrolled growth of cancer cells. We have attempted to elucidate the role of oncogenes and growth factors in the premalignant progression of human breast epithelial cells by using an immortalized, nontumorigenic, near-diploid human mammary epithelial cell line, HMT-3522, derived from a fibrocystic lesion and established in our laboratory. During propagation in tissue culture, the growth factor requirements of the HMT 3522 cells decreased simultaneously with an amplification and overexpression of the c-myc protooncogene. Other protooncogenes related to human breast cancer were unaltered with regard to gene copy number and expression. In passage 118, in which the most important growth factor still was epidermal growth factor (EGF), we were able to isolate an EGF-independent subline (S2). The EGF independence of S2 was accompanied by an overexpression of the mRNAs for epidermal growth factor receptor (EGF-R), transforming growth factor-alpha, and c-erb-B2 as compared to the EGF-dependent subline (S1). Moreover, by application of a blocking anti-EGF-R antibody, growth of S2 cells in EGF-free medium was inhibited significantly, indicating that EGF-R was involved in an autocrine loop probably with transforming growth factor-alpha as ligand. Neither the late passages of S1 cells nor S2 cells were tumorigenic after subcutaneous transplantation to athymic mice. Our results indicate that c-myc amplification and overexpression are correlated with a decreased requirement for growth factors. Even when these alterations are combined with immortalization and EGF independence, they are insufficient for malignant transformation of these human breast epithelial cells. PMID- 1737383 TI - CA 72-4 measurement of tumor-associated glycoprotein 72 (TAG-72) as a serum marker in the management of gastric carcinoma. AB - The presence of three distinct serum markers of carcinoma, tumor-associated glycoprotein 72 (TAG-72; as measured by the CA 72-4 assay), CA 19-9, and carcinoembryonic antigen (CEA), was evaluated in 194 patients diagnosed with either malignant (n = 94) or benign (n = 100) gastric disease. Of the 94 patients diagnosed with gastric carcinoma, the percentage of patients whose serum samples were positive for TAG-72, CA 19-9, or CEA was 42.6, 31.9, and 20.2%, respectively. Furthermore, fewer false positive samples were observed for TAG-72 than either CA 19-9 or CEA. The analysis of serum TAG-72, CA 19-9, and CEA levels in patients diagnosed with early (stage I and II) versus advanced (stage III and IV) disease revealed a significantly higher level of TAG-72 and CA 19-9 in the serum of patients with advanced stage gastric carcinoma. The serum samples were also analyzed to determine whether any advantage might be gained by simultaneously measuring two or more of the tumor markers. The data clearly indicate that the measurement of TAG-72 with CA 19-9 significantly increased the percentage of gastric carcinoma patients with positive serum levels of either antigen. This advantage was achieved with no significant increase in the number of false positives. Twenty-one patients were followed postsurgically for up to 3 years to determine whether the appearance or reappearance of TAG-72, CA 19-9, or CEA accurately predicted disease recurrence. Positive serum TAG-72 levels correlated with disease recurrence in 7 of 10 patients, compared with 5 and 2 patients for CA 19-9 and CEA, respectively. The findings suggest that serum TAG 72 as measured by the CA 72-4 assay may be a useful marker for late stage gastric carcinoma and its measurement alone or in combination with CA 19-9 may have utility in the clinical management of gastric carcinoma. PMID- 1737384 TI - Effectiveness of a lysyl chlorin p6/chlorin p6 mixture in photodynamic therapy of the subcutaneous 9L glioma in the rat. AB - A new photosensitizer, LCP, a combination of lysyl chlorin p6 and chlorin p6, was synthesized and tested for effectiveness in photodynamic therapy using s.c. implanted 9L glioma tumors in rats. Tumors were irradiated with 664-nm light 4 h after LCP injection. Mean intratumoral temperature elevations were less than 4 degrees C using a power density of 50 mW/cm2 for 33.3 min (100 J/cm2). Subsequent experiments examining histological changes and tumor regrowth used a power density of 50 mW/cm2 and total energy densities of 25, 50, and 100 J/cm2. Microscopically, an energy density-dependent coagulation necrosis of tumor cells occurred in treated tumors. Long term inhibition of tumor growth was achieved only at an energy density of 100 J/cm2. Side effects of treatment were seen only in the irradiated area and consisted of coagulation necrosis of normal tissues in rats treated at 50 and 100 J/cm2, including severe skin necrosis. Exposure of rats to fluorescent room light did not cause any macroscopically detectable skin damage. Our data indicate that photodynamic destruction of s.c. 9L glioma tumors using LCP as a photosensitizer results in significant tumor growth inhibition and that further study of LCP is warranted. PMID- 1737385 TI - Antitumoral and endocrine effects of (+)-vorozole in rats bearing dimethylbenzanthracene-induced mammary tumors. AB - The antitumoral activity of vorozole, a potent and specific nonsteroidal aromatase inhibitor, against 7,12-dimethylbenz(a)anthracene-induced estrogen dependent mammary adenocarcinoma was evaluated in 257 Sprague-Dawley rats. Twice daily p.o. administration of 1 and 5 mg/kg of the racemate R 76713 for 42 days induced almost complete regression of tumors, inhibited the appearance of new tumors, and reduced multiplicity of the remaining tumors. Antitumoral effects observed after ovariectomy or treatment with 5 mg/kg twice a day were not significantly different. R 76713, the racemate, (+)-vorozole (both at 2.5 mg/kg twice a day), and ovariectomy all similarly reduced tumor growth at 42 days by 90% or more, lowered the number of existing tumors, and prevented the appearance of new tumors. The less active levo-enantiomer (-)-vorozole at the same dose did not alter tumor growth. Vorozole reduced serum estradiol to the levels measured in ovariectomized animals. Serum progesterone levels were lowered, but to a much lesser extent than after ovariectomy, while serum luteinizing hormone and follicle-stimulating hormone concentrations increased, but also much less than after ovariectomy. On the other hand, the androgen levels, which remained undetectable or decreased after ovariectomy, markedly rose after vorozole treatment. These endocrine changes, observed in intact female rats, were not detected in ovariectomized animals demonstrating the ovarian origin of the endocrine changes induced by vorozole. PMID- 1737386 TI - Camptothecin induces differentiation and stimulates the expression of differentiation-related genes in U-937 human promonocytic leukemia cells. AB - We have studied the effect of the DNA topoisomerase I inhibitor camptothecin on growth, differentiation, and gene expression in U-937 human promonocytic leukemia cells. At a concentration of 20 nM, camptothecin caused significant DNA strand breakage and decreased the growth activity by accumulating cells preferentially at the G2 phase of the cycle. The growth arrest occurred concomitantly with an increase in cell size. Under those conditions, camptothecin induced differentiation, as demonstrated by (a) the capacity of the cells to generate reactive oxygen species, (b) the increase in the surface expression of the leukocyte integrins CD11b/CD18 and CD11c/CD18, (c) the increase in the cellular content of the intermediate filament protein vimentin, and (d) the decrease in the surface expression of the transferrin receptor. Camptothecin also induced the expression of differentiation markers in other human myeloid cells, namely, the promonocytic THP-1 and the myelomonocytic HL-60 cell lines. Northern blot assays revealed that camptothecin stimulated the expression of CD11b, CD11c, and vimentin at the mRNA level. Moreover, the drug increased the transcription rate of the vimentin gene, as shown by "run-on" transcription assays. PMID- 1737387 TI - A rationale for carboplatin treatment and abdominal hyperthermia in cancers restricted to the peritoneal cavity. AB - The purpose of this study was to optimize the treatment of cancers restricted to the peritoneal cavity by combining i.p. chemotherapy with abdominal hyperthermia. In vitro experiments demonstrated that the uptake of carboplatin into CC531 tumor cells was increased at temperatures higher than 41.5 degrees C at dose levels of 5 and 50% cell kill. Carboplatin-DNA adduct formation and cytotoxicity, however, were already increased at temperatures of about 40 degrees C, indicating that carboplatin-DNA adduct formation and consequently cytotoxicity could be enhanced by mild hyperthermia (temperatures in the range of 39-41.5 degrees C). CC531 tumor bearing rats were treated i.v. and i.p. with carboplatin (6.15 mg/kg) in combination with regional hyperthermia of the abdomen (41.5 degrees C for 1 h). The mean temperature was 41.5 +/- 0.3 degrees C (SD) in the peritoneal cavity and 40.5 +/- 0.3 degrees C in the esophagus. Enhanced platinum concentrations were found in peritoneal tumors (factor 3) and in kidney, liver, spleen, and lung (a factor 2 average), after the combined i.v. or i.p. carboplatin-hyperthermia treatment. Pharmacokinetic data of i.p. CBDCA combined with hyperthermia demonstrated an increased tumor exposure for total and ultrafiltered platinum in plasma. The areas under the concentration x time curve for total platinum at 37 degrees C and 41.5 degrees C were 69 and 210 microM/h, respectively; for ultrafiltered platinum these values were 47 and 173 microM/h. This may have been due to a slower elimination of platinum from the blood at the higher temperature (t1/2 beta for total platinum 99 and 156 min at 37 and 41.5 degrees C, respectively). The direct exposure of the tumor via the peritoneal fluid appeared to diminish, since the area under the curve for total platinum was lower at 41.5 degrees C than at 37 degrees C (576 microM/h versus 1255 microM/h, respectively). Our results indicate that the advantage of adding hyperthermia is caused by an increased drug exposure of the tumor via the circulation. This was supported by the fact that platinum concentrations in peritoneal tumors after carboplatin treatment at elevated temperatures were similar for the i.p. and i.v. routes. PMID- 1737388 TI - Nonglycolytic acidification of murine radiation-induced fibrosarcoma 1 tumor via 3-O-methyl-D-glucose monitored by 1H, 2H, 13C, and 31P nuclear magnetic resonance spectroscopy. AB - The effects of 3-O-methyl-D-glucose (3-OMG) on subcutaneously implanted murine radiation-induced fibrosarcoma 1 tumor were examined with 2H, 13C, and 31P nuclear magnetic resonance (NMR) in situ. Using 31P NMR, changes in tumor high energy phosphate metabolism were monitored for 2.5 h after i.p. administration of 3-OMG (8.1 g/kg body weight); tumor pH decreased by a mean maximum of 0.52 +/- 0.05 (SE) (n = 10), [PCr] decreased by 54%, [NTP] decreased by 35%, and [Pi] increased by 36%. Tumor blood flow, as measured by 2H NMR monitoring of D2O washout kinetics, decreased by 40% at 1 h and by 47% at 2 h after 3-OMG injection (n = 4). This substantial tumor acidification (pH decrease much greater than 0.1), expected to require a glycolytic substrate (Hwang et al., Cancer Res., 51: 3108-3118, 1991), is surprising in light of the previously documented metabolically inert nature of 3-OMG. In situ 13C NMR spectroscopy, following [6 13C]3-OMG i.p. injection, examined the possibility of the glycolytic metabolism of 3-OMG. However, only the C-6 resonance of 3-OMG was detected (n = 6); no resonances from [6-13C]3-OMG-6-phosphate or [3-13C]lactate were observed. These results confirmed that 3-OMG was not metabolized in radiation-induced fibrosarcoma 1 tumor. At the completion of the in situ 13C NMR experiments, tumors were freeze clamped, and perchloric acid extraction was performed. High resolution 1H NMR measurement of lactate concentrations showed no statistically significant difference in control tumor extracts (from mice not receiving i.p. injection; n = 5) and in tumor extracts from mice administered i.p. [6-13C]3-OMG (n = 5), indicating that there was no significant increase in lactate level in the tumor extracts from mice administered i.p. 3-OMG due to increased plasma glucose concentration. The results of these 1H and 13C NMR studies indicated that the radiation-induced fibrosarcoma 1 tumor acidification caused by i.p. administration of 3-OMG was not due to a direct (3-OMG----lactate) or an indirect (systemic glucose----lactate) increase in tumor lactic acid levels. PMID- 1737389 TI - Binding of aflatoxin B1 metabolites in extrahepatic tissues in fetal and infant mice and in adult mice with depleted glutathione levels. AB - Whole-body autoradiography of 3H-labeled aflatoxin B1 (AFB1) in adult C57BL mice pretreated with the glutathione (GSH)-depleting agent phorone showed accumulation of tissue-bound radioactivity in the nasal olfactory and respiratory mucosa, the mucosa of the nasopharyngeal duct, and the tracheal and esophageal mucosa, which was not seen in unpretreated adult mice. The altered distribution pictures induced by the phorone are probably related to decreased tissue levels of GSH. The AFB1 is likely to be bioactivated locally in the extrahepatic tissues; in nonpretreated mice the reactive AFB1 metabolite formed is probably scavenged by GSH via the action of glutathione-S-transferase, whereas in the mice with depleted GSH levels a binding to tissue macromolecules will instead take place. The mechanism indicated above is supported by results of in vitro experiments in which the nasal olfactory mucosa and the esophageal mucosa were shown to have a capacity to form tissue-bound 3H-AFB1 metabolites. This formation was decreased when the incubations were performed in the presence of GSH. In addition, the treatments of mice with phorone were shown to induce a strong GSH depletion in the nasal olfactory mucosa and the esophageal mucosa. In autoradiographic studies performed with 1- and 5-day-old infant mice a marked localization of bound 3H AFB1 metabolites was found in the nasal olfactory mucosa, and in the 5-day-old infant there was also a labeling of the mucosa of the nasopharyngeal duct, the pharyngeal and esophageal mucosa, and the tracheal mucosa. Experiments in vitro with the nasal olfactory mucosa of 5-day-old infants demonstrated a marked binding of 3H-AFB1 metabolites in this tissue. Incubations together with GSH decreased this binding, although the inhibition was less marked than in the adult animal. The in vivo accumulation of bound AFB1 metabolites in the extrahepatic tissues of the infant mice may be related to low glutathione-S-transferase (GST) activity in the tissues of the young animals. In addition, some extrahepatic tissues may have a considerable capacity to bioactivate the AFB1 at early age. Autoradiography of 3H-AFB1 in pregnant mice showed a labeling of the fetal nasal olfactory mucosa at day 18 but not at day 14 of gestation. This indicates that AFB1-bioactivating enzymes develop in the fetal nasal olfactory mucosa in late gestation. PMID- 1737390 TI - Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines. AB - The effects of the protein kinase C (PKC) activators, phorbol ester 12-O tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5 day cultures. Bryostatin 1 inhibited growth of only MCF-7 cells and only at a high dose (100 nM). However, bryostatin 1 completely antagonized the growth inhibition and morphological changes induced by TPA in MCF-7 cells. The divergent effects of these two agents are associated with differing effects on PKC activity and isoform expression in MCF-7 cells. TPA induced rapid translocation of the PKC alpha isozyme and PKC activity to the membrane fraction of MCF-7 cells. In contrast, bryostatin 1 treatment resulted in the loss of the PKC-alpha isozyme and PKC activity from both cytosolic and membrane compartments within 10 min of treatment. In coincubation assays the bryostatin 1 effect was dominant over that of TPA. Similar effects on PKC-alpha isozyme and PKC activity were seen in a second cell line whose growth was inhibited by TPA but not by bryostatin 1, MDA MB-468. In contrast, in the T47D cell line, where TPA was not growth inhibitory, TPA failed to induce translocation of PKC-alpha to the cell membrane. Bryostatin, however, still caused loss of PKC-alpha isozyme and PKC activity from cytosolic and membrane fractions. Thus, differential actions of bryostatin 1 and TPA on PKC activity and alpha-isoform level in the membrane-associated fraction of MCF-7 and MDA-MB-468 cells may account for the divergent effects of these two agents on cell growth and morphology. These results suggest that the PKC-alpha isoform may specifically play a role in inhibiting growth of human breast cancer cells. PMID- 1737391 TI - Effects of target antigen competition on distribution of monoclonal antibody to solid tumors. AB - Monoclonal antibody (MoAb) 11A and MoAb 13A recognize normal murine cell surface glycoproteins, which are also expressed in high concentrations on Line 1 lung carcinoma. Studies were initiated to examine the competition in vivo for radiolabeled MoAb between sites on the tumor versus sites on normal tissue. Quantitative 2-site assay of the alpha 6 beta 4 integrin recognized by MoAb 11A showed that major sites of expression are tumor, intestine, and skin. Microdistribution studies show that at doses of 125I-labeled MoAb 11A less than the total body antigen load, the MoAb bound to beta 4 endothelial cells with little extravasation to epithelial sites. As the MoAb dose was increased, and endothelial sites became saturated, deposition at epithelial sites including skin and tumor became apparent. Quantitative radioimmunoassay with MoAb 13A, recognizing CD44 (P100), demonstrated major sites of expression as tumor, intestine, liver and, to a lesser extent, spleen and skin. Microdistribution studies at low doses of 125I-labeled MoAb showed deposition mainly in the liver and spleen sinusoids, whereas higher doses were necessary to maximize MoAb accumulation in tumor. The rapid access of MoAb to target antigen is the most important parameter in efficient localization of MoAb. Access of antigen outside the vascular space is regulated at least in part by the permeability of the endothelial barrier. Of the organs studied, antigen accessibility increases in the following order: lung epithelium less than skin epithelium less than intestine and uterus epithelium less than epithelial tumors less than liver and spleen sinusoids less than intervascular sites. Antigens in easily accessible sites interact with MoAb first and must be saturated before MoAb will penetrate to less accessible areas. Thus, the extent of competition of antigen for available MoAb depends not only on the amount of antigen, but also on the site at which it is expressed. Doses that achieve maximum binding to tumor sites can be predicted if accurate target antigen quantities and sites of expression are known. PMID- 1737392 TI - Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice. AB - Since our aim was to isolate and identify new progression markers of human cutaneous melanoma, we applied the differential hybridization technique, in which we compared the gene expression in two subsequent stages of this progression. Tumors in nude mice arising after transplantation and serial passage in vivo of either the horizontally and early vertically growing part or the advanced vertically growing part of a primary melanoma of the same patient were used for this assay. This resulted in the isolation of a number of complementary DNA clones that were differentially expressed. Based on the marked difference in expression, one of them, designated pMW1, was chosen for further characterization and appeared to be coding for calcyclin, a cell cycle-regulated protein, belonging to a family of small calcium-binding proteins. Calcyclin expression was elevated in high-metastatic human melanoma cell lines in nude mice compared to low-metastatic ones. Immunoprecipitation of calcyclin showed that the differential expression at the RNA level is also reflected at the protein level. These findings show that expression of calcyclin is related to metastasis of human melanoma cell lines in nude mice and emphasize the role of this family of calcium-binding proteins in neoplastic progression as was reported for the mouse homologue of calcyclin and other members of the same family. PMID- 1737393 TI - Nuclear enlargement induced by hepatocarcinogens alters ploidy. AB - Treatment of rats with low doses of hepatocarcinogens is associated with a number of phenomena, including nuclear enlargement and altered nucleocytoplasmic compartmentation, which potentially reflect initiatory changes. Since a number of investigations have indicated that changes in ploidy may relate to the development of altered foci and/or hepatocellular carcinomas in liver, and since nuclear enlargement may be associated with changes in DNA content, we examined the ploidy of rat hepatocytes following essentially nontoxic low-dose carcinogen treatment. Treatments with thioacetamide, 2-acetylaminofluorene, or dimethylnitrosamine were all associated with a notable shift of nuclei from diploid to tetraploid, in the apparent absence of nuclear replication. These changes were similar in magnitude to that associated with the substantial liver regeneration induced by carbon tetrachloride. If it is argued that cell replication is a necessary prerequisite for the completion of initiation, these data suggest that there may be thresholds for initiation. PMID- 1737394 TI - Hepatitis B virus replication in well differentiated mouse hepatocyte cell lines immortalized by plasmid DNA. AB - The primary hepatocytes cultured from adult BALB/c mice were readily transfected by plasmid DNA and could be immortalized at a frequency of approximately 0.1 to 0.6 x 10(-7) cells/micrograms of the transfected DNA. There was no detectable plasmid DNA at the tenth cell passages. A total of five mouse hepatocyte cell lines were established. Most of them were tumorigenic. Three of the established mouse hepatocyte cell lines were well differentiated, since they expressed liver specific genes. Further transfection of these three well differentiated mouse hepatocyte cell lines with hepatitis B virus (HBV) DNA showed that the HBV transfected cells had integrated HBV genomes, HBV-specific mRNA transcripts, and expression of hepatitis B surface and hepatitis B core antigens. One of the lines, ML-3Neo (HBV), even secreted HBV-like particles. Furthermore, circulating hepatitis B surface antigens were detected in the sera of BALB/c mice bearing ML 3Neo (HBV) tumors. These cell lines provide a convenient model for future studies on the host immune reaction against HBV and on the transformation of hepatocytes by HBV and other cellular oncogenes and the determination of their effects on hepatocellular differentiation. PMID- 1737395 TI - Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation. AB - The incubation of human mammary adenocarcinoma cells (BT-20) with tumor necrosis factor alpha in the absence or presence of cycloheximide resulted in progressive DNA fragmentation. This was preceded by a sustained increase in intracellular free Ca2+ concentration and was not detected in cells pretreated with intracellular Ca2+ chelators, calmodulin antagonists, or activators of protein kinase C. Image analysis of fura-2-loaded BT-20 cells treated with tumor necrosis factor alpha revealed that, in many cells, the initial increase in Ca2+ level occurred in a cellular region that corresponded to the localization of the nucleus. Our findings suggest that tumor necrosis factor alpha can promote an increase in intranuclear free Ca2+ which, in turn, may stimulate Ca(2+)-dependent endonuclease activity, resulting in DNA fragmentation and apoptosis. PMID- 1737396 TI - Site-dependent differences in sensitivity of LOX human melanoma tumors in nude rats to dacarbazine and mitozolomide, but not to doxorubicin and cisplatin. AB - Three model systems involving LOX human malignant melanoma cells in nude rats were used to compare the chemosensitivity of tumors growing in different tissues. Groups of 4-18 rats with either s.c. xenografts, lung tumor colonies, or bone metastases were treated with cisplatin, doxorubicin, dacarbazine, or mitozolomide. The antitumor effect in the s.c. model was expressed as specific growth delay, and in the experimental metastasis studies as relative increase in life span (RILS), calculated on the basis of observed disease-free survival. Cisplatin had a moderate but significant effect on the progression of LOX tumor growth in all three systems. Doxorubicin was clearly more efficacious, but for both drugs tumor-free survivors were rare or absent. Importantly, for each of the compounds the levels of response were roughly the same in all three models, with specific growth delay and RILS values in the range of 0.2-0.3 for cisplatin and 0.5-0.9 for doxorubicin. In contrast, a significant site-dependent difference in sensitivity of the LOX tumors was observed for two alkylating agents. Thus, dacarbazine, which temporarily caused complete regression of s.c. xenografts (specific growth delay = 21.0), showed a moderate activity in the lung tumor model (RILS = 1.0) but had only a limited effect (RILS = 0.4) on bone metastases. Mitozolomide gave a curative effect in 6 of 10 animals with s.c. and in 4 of 4 animals with lung tumors, whereas in the bone metastasis model it was only slightly superior to doxorubicin (RILS = 1.1). In preliminary attempts to elucidate the underlying mechanisms, no site-dependent differences in drug distribution and in two cellular detoxifying systems were detected. The data demonstrate the usefulness of the LOX models for studying the clinically relevant problem of site-dependent tumor response to chemotherapy. PMID- 1737397 TI - In vitro and in vivo enhancement of ricin-A chain immunotoxin activity by novel indolizine calcium channel blockers: delayed intracellular degradation linked to lipidosis induction. AB - With regard to increasing the clinical potential of ricin A-chain immunotoxins (RTA-ITs), a novel class of calcium channel blockers, indolizines SR33557 [2 isopropyl-1-[4-(3-N-methyl-N-(3,4-dimethoxy-beta- phenethyl)amino)propyloxy)benzenesulfonyl))indolizine] and SR33287 [isopropyl-2 ((1-butylamino-3-propyl)oxy-4-benzoyl)-3-indolizine], were evaluated for their ability to enhance RTA-IT activity in vitro and in vivo. Five microM SR33287 and 5 microM SR33557 were potent enhancers of both anti-Thy 1.2 AT15E RTA-IT (84- and 64-fold, respectively) on T2 cells and anti-CD5 T101 (622- and 538-fold) and T101 F(ab')2 RTA-IT (34- and 28-fold) on CEM III cells. This was superior to the effect achieved by both 10 microM verapamil and 10 mM NH4Cl, albeit slightly inferior to that of 50 nM monensin and 5 microM perhexiline. Murine T2 lymphoma cells bearing the Thy 1.2 antigen were injected i.v. in Thy 1.2 (-) BL. 1.1 mice (median survival time, 17.7 days). Intravenous treatment with 10 micrograms of AT15E RTA-IT prolonged the survival of mice (median survival time, 26.8 days). When 400 micrograms of SR33287 were coinjected i.v. with 10 micrograms of AT15E RTA-IT, mouse survival was further increased, with 5 of 6 mice surviving, disease free, over 42 days. SR33287 had a significant impact on the intracellular routing of 125I-AT15E RTA-IT, which induced a greater than 2-fold increase in intracellular intact AT15E RTA-IT at 90 min. This effect on RTA-IT half-life was distinctly different from that observed with either NH4Cl or monensin and may be linked to the inhibition of acid lysosomal sphingomyelinase by SR33287, leading to cellular lipidosis. In conclusion, indolizines appear to be promising agents not only for immunotoxin enhancement but also for increasing the activity of any number of targeted therapeutic agents where modifying either the intracellular routing or increasing the intracellular half-life of the ligand would be beneficial to its cytotoxic activity. PMID- 1737398 TI - Induction of covalent DNA adducts in rodents by tamoxifen. AB - The antiestrogen tamoxifen, increasingly used as adjuvant treatment for breast cancer, has been found to covalently modify DNA of rodents. For instance, the liver DNA of female Sprague-Dawley rats treated with a single injection of tamoxifen contained two DNA adducts. Four additional DNA adducts were formed and adduct concentrations increased 5- 7- and 10-15-fold after three and six tamoxifen injections, respectively, from levels observed after a single dose. The accumulation of DNA adducts with repeated administrations of tamoxifen to rodents may make this drug a poor choice for the chronic preventative treatment of breast cancer. PMID- 1737399 TI - Inverse relationship between trk expression and N-myc amplification in human neuroblastomas. AB - We examined the expression of the trk protooncogene in a series of 82 neuroblastomas to determine its relationship to N-myc amplification and expression, disease stage, patient age, and survival. We found that virtually all stage I, II, and IV-S patients had moderate to high levels of trk expression, whereas most advanced stage neuroblastomas had low or absent levels. All but one tumor with N-myc amplification had low or absent trk expression, and the one exception was regressing at the time it was resected. Conversely, all neuroblastomas identified by mass screening had moderate to high expression of trk, and all these patients are surviving. Thus, trk expression was associated with an absence of N-myc amplification, lower disease stage, lower patient age, and favorable outcome. Tumors with high trk expression may be more likely to differentiate, regress spontaneously, or respond well to therapy. PMID- 1737400 TI - Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. AB - Thyroid neoplasms show a wide variety of lesions varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There has been some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. In the present study, mutations in the p53 gene were investigated by direct sequencing analysis after polymerase chain reaction amplification of exons 5 to 8, using paraffin-embedded primary tumors and cultured cells. No mutations in exons 5 to 8 were detected in 10 differentiated papillary adenocarcinomas, whereas 6 of 7 undifferentiated carcinomas were found to carry base substitution mutations. Sequencing analysis confirmed mutations at codons 135 (TGC----TGT), 141 (CCC----CCT), 178 (CAC----GAC), 213 (CGA----TGA), 248 (CGG----CAG, CGG--- TGG), and 273 (CGT----TGT). The spectrum of mutations (G:C to A:T transitions in 7 of 8) might be a specific feature of the spontaneous cancers. The results strongly suggest that, in human thyroid glands, p53 mutations play a crucial role in the progression of differentiated carcinomas to undifferentiated ones. PMID- 1737401 TI - Partial purification of a human DNA glycosylase acting on the cyclic carcinogen adduct 1,N6-ethenodeoxyadenosine. AB - We previously reported that a variety of human cells and tissues contained a Mr35,000 DNA-binding protein which selectively recognized a single 1,N6 ethenoadenine in a defined 25-base double-stranded oligonucleotide (B. Rydberg et al., Proc. Natl. Acad. Sci. USA, 88: 6839-6842, 1991). We now demonstrate that incubation of the same duplex with 50-fold partially purified binding protein from human placenta results in release of the free 1,N6-ethenoadenine base, indicative of DNA glycosylase action. This enzyme activity appears unique in that it excises a cyclic adduct resulting from a known human carcinogen. PMID- 1737402 TI - Adenosine's effectiveness in long RP' re-entrant tachycardia: additional evidence of the decremental qualities of the retrograde limb. AB - Adenosine's ability to terminate atrioventricular (AV) re-entrant supraventricular tachycardia is well documented. Typically, termination occurs as a consequence of transient conduction block in the atrioventricular node, a tissue with decremental qualities. However, the atrioventricular node is not always the site of action when adenosine is used on the re-entrant types of long RP' tachycardias. These tachycardias are, in part, characterized by the decremental qualities of the retrograde limb of the tachycardia circuit, which, in turn, are typically exemplified by retrograde Wenckebach during ventricular (VVI) pacing during intracardiac electrophysiology studies. This case report involves adenosine's ability to block conduction in the retrograde limb of the permanent form of junctional reciprocating tachycardia to provide further evidence as to the AV "nodelike" decremental qualities of this limb. PMID- 1737403 TI - Catastrophic thrombus development despite systemic heparinization during coronary angioplasty: possible relationship to nonionic contrast. AB - Two cases of catastrophic thrombus formation during coronary angioplasty occurred shortly after the operators began using nonionic contrast. This occurred despite systemic heparinization, the adequacy of which was documented by activated clotting times (ACT). Both cases were resistant to balloon inflation and one was refractory to intracoronary thrombolysis. There is a considerable body of evidence documenting that low-osmolality contrast media, especially those that are nonionic, have less anticoagulant effect than standard contrast media. Several reports have also been published suggesting possible relationships between nonionic contrast and intravascular thrombus formation during coronary angiography and angioplasty. These data are reviewed and recommendations made for utilization of these contrast media. PMID- 1737404 TI - Documentation of successful treatment of prosthetic mitral valve thrombosis with intravenous urokinase infusion for twenty-four hours. AB - Prosthetic valve thrombosis is a life-threatening situation requiring prompt diagnosis and treatment. Treatment has usually been surgical and has been associated with a high mortality. Thrombolytic therapy is a therapeutic alternative to surgery and has been successful in a number of cases. This report concerns the technique used to diagnose the condition, treatment strategy, and documentation of the results of therapy. PMID- 1737405 TI - John Hunter (1728-1793). PMID- 1737406 TI - Acronyms and myocardial infarction studies. PMID- 1737407 TI - The postcardiac injury syndromes. AB - Late pericarditis following myocardial infarction, cardiac surgery, or trauma is referred to as postmyocardial infarction syndrome (PMIS) or postcardiotomy syndrome (PCS), respectively. The term postcardiac injury syndrome (PCIS) is used to encompass both these entities. PCIS is characterized by fever, pleuropericardial pain, pericarditis, and pulmonary involvement. Abnormal laboratory findings include leukocytosis, high sedimentation rate, and chest x ray abnormalities of pleural effusion with or without pulmonary infiltrates. Evidence supports an immunopathic etiology; viruses may play a contributing role. The course is benign but rare complications include tamponade, constriction, anemia, and coronary bypass graft occlusion. Anti-inflammatory agents are helpful; indo-methacin and steroids are preferably avoided. Rarely, PMIS-like syndrome may occur following pulmonary embolism. Anticoagulation and steroids have been used successfully in the latter situation. PMID- 1737408 TI - Oblique cine MRI for the evaluation of aortic regurgitation: comparison with cineangiography. AB - The results of oblique cine magnetic resonance imaging (MRI) through a long axis slice of the left ventricle in 40 patients was compared with cineangiography in order to determine the usefulness of cine MR imaging for the evaluation of aortic regurgitation (AR). A diastolic dark low-intensity flow signal extending from the aortic valve into the left ventricle was seen in all 30 patients with AR, and in none of the 10 patients without AR. The length and area of the low-intensity signal due to the regurgitant flow were planimetered, and the ratio to the length and area of the left ventricle was calculated. The best correlation with angiography was with the ratio of the area of the low-intensity signal (ALIS) to the area of the left ventricle (ALV); it correctly classified the degree of regurgitation in 28 of the 30 patients (93.3%). The ALIS/ALV ratio was under 25% in all 11 patients with angiographic mild AR, 26-50% in 10 of the 11 patients with moderate AR, and over 51% in 7 of the 8 patients with severe AR. Thus the results point to a high degree of correlation between long axis oblique cine MRI and cineangiography in the identification of AR and in providing a semiquantitative estimation of its severity. PMID- 1737409 TI - Changes of diastolic function induced by cigarette smoking: an echocardiographic study in patients with coronary artery disease. AB - In 28 chronic smokers (11 women, 17 men, 53 +/- 10 years old) with coronary artery disease (greater than 75% stenosis), left ventricular (LV) relaxation and filling behavior was assessed before and after inhalation of 0.9 mg nicotine (1 cigarette) by echocardiography. The following acute nicotine-mediated changes were noted (one-sided Wilcoxon test): heart rate increased from 67 to 81 beats/min (p greater than .001); the early diastolic flow (E wave) integral decreased from 49 to 39 mm (p less than .001); the late diastolic flow integral (A wave) increased from 36 to 41 mm (p less than .01). Consecutively, the ratio between E and A wave flow integrals decreased from 1.4 to 0.9 (p less than .001); the atrial contribution to LV filling rose from 42 to 53% (p less than .001); and the isovolumetric relaxation period increased from 89 to 122 ms (p less than .001). In cigarette smokers with coronary artery disease acute administration of nicotine hence causes a shift of mitral blood flow from early (E wave) to late (A wave) diastole and a prolongation of the isovolumetric relaxation time. Thus, cigarette smoking significantly affects LV diastolic function independently of its role as a risk factor for coronary atherosclerosis. PMID- 1737410 TI - Coronary hemodynamic effects of systemic thrombolysis in patients with unstable angina. AB - Intracoronary (i.c.) thrombus is a frequent finding in patients with unstable angina (UA). Accordingly, thrombolytic treatment could be beneficial, as resolution of thrombus might result in increased delivery of blood flow to the ischemic regions. To test this hypothesis, we studied 13 patients with active UA and ST-segment shift in the anterior leads. Coronary angiography was performed and great cardiac vein blood flow (GCVF; thermodilution) was measured in all patients 25 +/- 14 h after the last chest pain episode. Following angiography, patients received i.v. urokinase (UK: 1,000,000 IU/30 min); aortic pressure and GCVF were measured before and every 10 min following drug infusion, for a total time of 90 min. At baseline angiography, 5 of 13 patients (Group 1) had evidence of i.c. thrombus (intraluminal filling defect or thrombotic subocclusion) in the ischemia-related left coronary artery, whereas 8 patients (Group 2) did not. Group analysis showed that UK increased GCVF and decreased anterior coronary resistance in Group 1 (respectively, from 86 +/- 33 to 114 +/- 41 ml/min: p less than 0.005; and from 1.37 +/- 0.68 to 1.01 +/- 0.44 mmHg/ml/min: p less than 0.05) but not in Group 2 (both: p = NS). In conclusion, UK has been shown to increase regional coronary blood flow in selected patients presenting with active UA, as well as evidence of i.c. thrombus at early angiography. Heterogeneity of angiographic findings could explain controversies in trials dealing with thrombolysis in UA. PMID- 1737411 TI - Effect of diuretic therapy on the electrocardiographic response to exercise. AB - For nearly 30 years clinicians have assumed that diuretic therapy, per se, even in the absence of clinical hypokalemia, can cause false-positive exercise ST segment responses. The precept has stubbornly persisted in the literature and in the day-to-day interpretation of exercise tests in clinical settings. The assumption probably originated with very early studies of patients on diuretics, in which other causes of false-positive tests were not excluded. This study was undertaken to show that diuretic therapy alone is not sufficient to cause ST depression. Twenty healthy male volunteers, aged 18 to 35, with normal history and physical examinations, echocardiograms, electrocardiograms, serum electrolytes, renal function tests and exercise tests, took 50 mg of hydrochlorothiazide daily for four weeks. Exercise tests, serum electrolytes, and renal function tests were repeated at Weeks 2 and 4. The administration of the diuretic resulted in a statistically significant reduction in serum potassium (from 4.37 +/- 0.37 to 3.96 +/- 0.28, and 3.94 +/- 0.31 mEq/l at 2 and 4 weeks, respectively). There were no abnormal ST-segment shifts on any of the exercise tests. It is concluded that exercise-induced ST-segment shifts in otherwise healthy young male normokalemic subjects who are taking diuretics should not be ascribed to a false-positive response to diuretics. PMID- 1737412 TI - Paradoxical effect of long-term treatment of nifedipine on total ischemic load in patients with stable angina pectoris. AB - In 50 patients with stable effort angina the effect of three drugs, metoprolol, nifedipine, and diltiazem was assessed by analyzing exercise stress test response and ambulatory ECG recordings. Both metoprolol and diltiazem caused a significant increase in time to ischemic threshold during exercise and a significant decrease of maximum ST-segment depression (during exercise and ambulatory ECG monitoring) and in the average number of daily ischemic episodes. Only metoprolol significantly reduced heart rate and rate-pressure product at the ischemic threshold during exercise. In the group of patients treated with nifedipine no significant improvement was observed in exercise tolerance or in number of ischemic episodes/24 h. Moreover, the subset of nonresponders in the two methods was larger than in the other two groups. In some of these patients a clearcut worsening of total ischemic load was observed, despite the control of symptoms. This adverse effect might be attributed to the different consequences of the vasodilatory effect of nifedipine on blood flow through stenosed vessels. PMID- 1737413 TI - Temporal bone fractures in children: a review with emphasis on long-term sequelae. AB - A 10-year retrospective study of pediatric basilar skull fractures identified 120 patients with temporal bone fractures, of which 92 had otolaryngologic and audiologic evaluations. The otologic data provide documentation of the nature, common physical findings, complications, and management of these fractures. The prognosis of hearing impairment in children caused by temporal bone fractures is elucidated, as 76 of the 92 patients were available for long-term follow-up. Close interaction between involved services evaluating and treating pediatric trauma cases is mandatory for optimal patient outcome. A literature review of the presentation, complications, and management of pediatric temporal bone fractures is presented. PMID- 1737414 TI - Ohio's infant hearing screening and assessment program. A decade in development. AB - The early detection of hearing impairments in infants is essential to the initiation of medical and educational services which will enhance optimal development of communication and social skills. Ohio has successfully implemented a legislatively mandated two-tiered Infant Hearing Screening and Assessment Program. This statewide screening program is in accordance with the child find and early intervention services requirements of P.L. 99-457. PMID- 1737415 TI - An open letter to the pediatrician: hearing loss in children. PMID- 1737416 TI - Nasal obstruction in the neonate and infant. AB - The neonate is a preferential nasal breather; therefore, nasal obstruction in the neonatal period may cause significant sequelae. Although the uncommon choanal atresia is the main condition to be excluded, many other possible causes exist. A systematic approach to the workings of nasal obstruction in the neonate and infant is outlined so that appropriate management can be instituted. PMID- 1737417 TI - The current management of sinusitis in children. AB - The paranasal sinuses are common sites of infection in children. The diagnosis of sinusitis may be challenging because the sinus cavities are small and variably contoured, the clinical manifestations are often nonspecific, and the radiologic findings may be equivocal. Because many local and systemic factors contribute to sinusitis in children, the therapeutic regimens vary. In addition to conventional medical approaches, new surgical procedures and improved anesthetic techniques have made functional endonasal sinus surgery an excellent management tool for selected patients with chronic or recurrent disease. PMID- 1737418 TI - The role of computed tomography in the diagnosis of subperiosteal abscess of the orbit. AB - Periorbital cellulitis is a frequent complication of sinusitis in children. Subperiosteal abscess (SPA), however, is an uncommon sequela and may lead to serious complications if not promptly and adequately treated. A series of 13 consecutive patients who underwent orbital computed tomographic (CT) scans from January 1, 1986, to June 30, 1989, to investigate the possibility of SPA were reviewed. As demonstrated in this series, the diagnosis of subperiosteal abscess remains a clinical one that may be supported, but not determined, by an orbital CT scan. Cautious interpretation of these studies is advocated. Aggressive surgical therapy in appropriate clinical situations will lead to more rapid resolution of the disease process and fewer complications. PMID- 1737419 TI - New concepts in care of the pediatric ear and related structures. PMID- 1737420 TI - Neonatal respiratory distress secondary to an obstructing nasopharyngeal dermoid. AB - A case presentation of a newborn infant with intermittent, complete airway obstruction secondary to a pedunculated nasopharyngeal dermoid is presented. The differential diagnosis of obstructing nasopharyngeal lesions of the neonatal period is discussed, and an organized management strategy is proposed. PMID- 1737421 TI - Stridor in infants and children: ambulatory evaluation and operative diagnosis. AB - The presence of stridor in the young child suggests a congenital or acquired abnormality of the large diameter airways. The diagnostic evaluation of the stridulous child is discussed. Emphasis is placed on those outpatient examination techniques and radiographic studies which can define the nature of the offending airway lesion(s). PMID- 1737422 TI - The old and new of acute laryngotracheal infections. AB - Laryngotracheal infections in childhood frequently result in airway obstruction, the major symptom of which is stridor. The primary aims of management are to establish a diagnosis rapidly and to maintain or secure the child's airway. Medical treatment and airway stabilization measures vary for the three most prevalent laryngotracheal infections--supraglottitis, laryngotracheitis, and bacterial tracheitis--as well as for older and newer infectious airway entities. PMID- 1737423 TI - Diagnosis of acute thoracic aortic dissection using combined echocardiography and computed tomography. AB - Acute dissection of the thoracic aorta is a life-threatening emergency requiring a diagnosis which is rapid, accurate and safe, and which will distinguish between dissections involving the ascending and descending aorta. In the absence of any general agreement on the best method of making this diagnosis we studied the use of combined echocardiography and contrast-enhanced computed tomography (CT) to diagnose acute aortic dissection. Over a 3 year period 23 patients were investigated in this way. Aortic dissection was demonstrated in 18 cases, involving the ascending aorta in 15, and the descending aorta alone in three. The diagnosis of aortic dissection was confirmed in 13 patients at surgery, in one at aortography and in one at autopsy. Three patients died without surgery or autopsy being performed to confirm the diagnosis and the subsequently which accounted for their symptoms. This combined approach has proved a valuable and safe means of investigating aortic dissection. PMID- 1737424 TI - Computed tomography of paranasopharyngeal spaces: normal variations and criteria for tumour extension. AB - In 137 normal CT scans of the nasopharynx, the parapharyngeal spaces at the nasopharynx level were asymmetrical in 30%. Their difference in width and distance from the midline was greater than 1 mm in 51% and 44% respectively. Fat was absent in the interpterygoid fascia in 20%, in the alar fascia in 28%, in the prevertebral space in 35%, and in the retropharyngeal space in 99% of patients. Assessment of tumour extension to the paranasopharyngeal space usually relies on symmetry and fascial fat planes. As either feature may not be present in the normal person, the relation of the tumour to two lines representing two fascial planes is proposed as a complementary method for the evaluation of tumour extension. PMID- 1737425 TI - Does conventional tomography still have a place in glottic cancer evaluation? AB - Computed tomography (CT) can detect laryngeal cancer invading the pre-epiglottic, paraglottic spaces, laryngeal cartilages, and soft tissues, but in T1 and limited T2 tumours its main value is in evaluating subglottic extent. Conventional tomography in the coronal plane has been used with reasonable success to detect both subglottic and ventricular invasion and is less expensive than CT. Twenty nine cases of glottic carcinoma of all stages were examined clinically, endoscopically and radiographically by both coronal conventional tomography and CT. The results of these imaging studies are compared in this investigation, stressing their relationship to clinical findings (and stage), especially vocal and cord mobility. Coronal conventional tomography was found to be as accurate as CT for sublottic spread in nine cases of T1 and T2A cancer with normal vocal cord mobility. Conventional tomography had a slight tendency to overestimate ventricular and false cord involvement (two out of seven patients) with T1 glottic cancer. When mobility was impaired (four cases) or absent (15 cases), CT added data which changed staging and/or treatment plan in six cases. In seven others it was suggestive of a more advanced stage. PMID- 1737426 TI - Computed tomographic assessment of patients following radical surgery for malignant mesothelioma. AB - Serial computed tomographic (CT) scans of the thorax and upper abdomen were performed in eight patients following radical surgery (pleuro-pneumonectomy) for diffuse malignant mesothelioma of the pleura. The post-operative appearances included a well defined membrane lining the pleuro-pneumonectomy space in seven cases; in two cases this resembled the original tumour. In six patients there was upward abdominal visceral displacement on the side of the surgery due to diaphragmatic resection; this resulted in contralateral mediastinal shift in four patients. One patient required a diaphragmatic prosthesis which produced a distinctive CT appearance. CT suggested recurrent mesothelioma in five cases. Although two patients had evidence of intrathoracic recurrence, in three patients the only feature was the non-specific finding of abdominal ascites. The normal CT appearances after pleuro-pneumonectomy should be recognized to facilitate radiological interpretation. With careful application CT is of value for the assessment of recurrent disease in patients following radical surgery for malignant mesothelioma. PMID- 1737427 TI - Case report: pancreatic mediastinal pseudocyst--an unusual cause of palpitations. AB - We describe a case of pancreatic mediastinal pseudocyst which presented atypically with palpitations due to marked cardiac compression. Computed tomography (CT) showed a large abdominal pseudocyst extending through the diaphragm into the posterior mediastinum. Surgical drainage produced rapid symptomatic relief and the pseudocyst resolved completely within 2 months. PMID- 1737428 TI - Case report: metadiaphyseal chondroblastoma. PMID- 1737429 TI - Case report: CT and MRI of the cauda equina syndrome in ankylosing spondylitis. AB - The clinical and radiological findings in a patient with long-standing ankylosing spondylitis who developed the clinical features of a cauda equina syndrome are presented. CT and MRI revealed characteristic expansion of the lumbar spinal canal with scalloping of the laminae and spinous processes related to the presence of dorsal dural diverticulae. MRI permitted confident exclusion of other intradural pathology without recourse to invasive investigations. PMID- 1737430 TI - Case report: heparin-induced thrombocytopenia--a complication presenting to the vascular radiologist. AB - Heparin-induced thrombocytopenia is an infrequent complication of heparin which causes thrombocytopenia and thrombosis. The vascular radiologist can expect to come across several cases in his/her career. A high index of suspicion is required for early diagnosis. This may befall the radiologist who is asked to provide thrombolytic treatment in a heparinized patient. We present such a case and discuss the clinical presentation, pathogenesis and management of heparin induced thrombocytopenia. PMID- 1737431 TI - Case report: calcified brain metastases from an osteogenic sarcoma. PMID- 1737432 TI - Diagnosis of peripheral haemangiomas. PMID- 1737433 TI - Peritoneal mesothelioma: the role of computed tomography in diagnosis and follow up. AB - Computed tomography (CT) was performed on 15 patients with proven peritoneal mesothelioma. Eight of these patients underwent follow-up CT. It was found that a discrete and measurable mass is unusual in comparison with the common occurrence of ascites and that therefore CT has little role in quantifying the disease. Ascites is usually a prominent feature. Other features (e.g. omental infiltration) were evaluated and these could be used to assess disease progression. PMID- 1737434 TI - Duplex Doppler US in patients with medical renal disease: resistive index vs serum creatinine level. AB - The relationship between resistive index of arterial Doppler waveform of the native kidney and serum creatinine level has been studied using duplex Doppler sonography in 40 patients with medical renal disease and 28 normal controls. The resistive index of the normal control group and the medical renal disease group was 0.627 +/- 0.042 and 0.823 +/- 0.237, respectively, with statistically significant difference. In the group with medical renal disease, there was a statistically significant correlation between the resistive index and the level of serum creatinine. The study suggests that duplex Doppler sonography may be helpful in evaluation of renal functional status in patients with medical renal disease. PMID- 1737435 TI - Pancreatic and renal mobility. AB - One hundred and forty-five patients undergoing ultrasound examination for unrelated symptomatology were examined with respect to pancreatic position. Patients likely to have distorted upper abdominal anatomy were excluded. All patients were examined in the supine and left posterior oblique positions in the sagittal and transverse planes. The position of the head of the pancreas was noted in the following positions: pre-caval, pre-aortic and to the left of the aorta. The pancreas was not visualized in both positions in 25 patients, and these were excluded from the study. The pancreas changed position with patient movement in 45 patients. In eight females a change in position of the right kidney was also noted. This study demonstrates that pancreatic and to a lesser extent renal mobility is common, particularly in women. Attention is drawn to this finding which may cause distortion of the biliary and pancreatic anatomy. The altered landmarks may cause confusion in the interpretation of normal and abnormal structures. PMID- 1737436 TI - Pancreatic pseudocysts: treated with dual drainage. AB - Four patients with retrogastric pancreatic pseudocysts were successfully treated by the combined placement of a transgastric external drain and a cystogastric stent. We describe the advantages of using external transgastric drainage along with the cystogastric stent. PMID- 1737437 TI - Radiological appearances of small intestinal leiomyomas. AB - During a 5 year period we have identified leiomyomas of the small intestine in six patients using enteroclysis. Gastrointestinal bleeding were the presenting symptoms in five and partial small bowel obstruction in one. The time interval between the onset of symptoms and radiological diagnosis ranged between 3 months and 5 years. All patients had previously been investigated by a number of endoscopic and barium radiology examinations and one had undergone a nondiagnostic laparotomy. The jejunum was the site of involvement in one patient and the ileum in five. The growth was intraluminal in two cases, extraluminal in three and bidirectional (dumb-bell) in one. Radiological appearances included round or broad-based semilunar intraluminal filling defects with encroachment of the lumen, or intussusception, displacement and/or indentation of the intestinal wall with effacement of the overlying mucosa or an ulcer crater, tenting deformity and mass effect on neighbouring loops. All six patients came to operation. Pre-operative radiological diagnosis was correct in five and suggestive in one. There was excellent correlation between the radiological appearances and morphology of the pathology specimens. PMID- 1737438 TI - Focused microbiologic surveillance by specific hospital unit as a sensitive means of defining antimicrobial resistance problems. AB - An annual summary of susceptibility patterns for the predominant clinical isolates from hospitalized patients can be of considerable assistance in selecting antimicrobial agents for sepsis of unclear etiology, as well as for guiding empiric therapy for other serious infections. Yearly summaries of the susceptibility patterns of the predominant clinical isolates from all patients hospitalized at Vanderbilt University Hospital (VUH) from July 1987 through June 1991 revealed only minor differences over time in susceptibility patterns. However, the clinical impression of physicians treating patients in various intensive care units (ICUs) was that there were serious resistance problems in some units. To better define the prevalence of clinical isolates and their susceptibility patterns for patients within ICUs at VUH, we utilized a "focused microbiologic surveillance" technique that addressed each unit separately. Both the predominant clinical isolates and their susceptibility patterns were determined and compared with those from the hospital as a whole. Because susceptibility patterns of clinical isolates by site of infection within these units were considered important, we also reviewed the summaries of susceptibility patterns for blood, sputum, and urine isolates from patients in ICUs and compared these with the summaries from each ICU and from the hospital. No major resistance problems were identified on a hospital-wide basis. In contrast, focused microbiologic surveillance by specific hospital ICU revealed important differences in the prevalence of pathogens among units and at different times. In 1987, Pseudomonas aeruginosa was the single most common Gram-negative organism isolated in the neonatal unit, while Acinetobacter spp. were rarely isolated. By 1991, this trend was completely reversed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737439 TI - Comparison of susceptibility to beta-lactam antimicrobial agents among bacteria isolated from intensive care units. AB - Evaluating microbial isolation and susceptibility patterns from institutional settings is a well-established component of ongoing infection control activities. At the University of Michigan Hospitals, susceptibility profiles for selected bacteria tested from 1984 to 1989 were analyzed for major changes in the percentage of organisms susceptible to beta-lactam antimicrobials. Data on bacteria isolated from respiratory specimens obtained from 1433 patients in intensive care units (ICUs) during a 10-month interval were compared with like data obtained from 750 non-ICU patients. Antimicrobial agents studied were chosen based on hospital formulary availability and prevailing usage in the institution. Susceptible and moderately susceptible categories were combined for purposes of reporting, since empiric therapeutic doses would cover strains having both susceptibility levels. Antimicrobic susceptibilities were compared and differences analyzed among the ICUs. Major shifts in susceptibility were noted during the 5-year period. The incidence and susceptibility profiles of the microorganisms varied considerably between ICU and non-ICU patients. Pseudomonas aeruginosa isolates from individual ICUs showed large variations in prevailing susceptibilities, with the burn unit harboring the most resistant strains. However, the neurological, surgical, and critical care medicine units also showed large numbers of antimicrobial-resistant pseudomonads. Among Enterobacter cloacae isolates, only imipenem showed a high level of activity against both ICU and total hospital isolates. When examined by individual ICU, however, imipenem resistance was seen in the general medicine and burn units. The burn and pediatric ICUs showed increased rates of recovery of beta-lactam-resistant E. cloacae isolates, although significantly high resistance rates were seen throughout all ICUs. The surgical ICU was noted to have an abnormally high incidence of lower respiratory infections caused by P. aeruginosa. The antibiogram indicated that one possible epidemic strain was involved. However, when the isolates were subjected to fatty-acid profiling by gas-liquid chromatography, it was found that cross-contamination with five discernible strains had occurred among the ten patients tested. These preliminary data suggest that resistant pseudomonads can be harbored and spread within an ICU, and that the ICU can act as a reservoir of resistance that is spread to a "step-down" unit. PMID- 1737440 TI - The current and future impact of antimicrobial resistance among nosocomial bacterial pathogens. AB - The selection of drug-resistant microorganisms has generally been associated with the widespread use of antimicrobial agents. The emergence of these antimicrobial resistance has an undesirable impact that often severely limits the use of these drugs that could have otherwise been identified as "drugs of first choice." Among the most serious drug-resistance problems, the chromosomally mediated type -I beta-lactamase mechanism has become more common among the infecting Gram-negative bacteria. Type-I beta-lactamases are routinely identified in Enterobacter spp., Citrobacter freundii, Proteus vulgaris, Pseudomonas spp., Providencia spp., Morganella spp., Serratia spp., and various nonfermenters, including Acinetobacter spp., and can be induced to high production when exposed to certain beta-lactam antibiotics (for example, ceftazidime or cefoxitin). These organisms can also undergo spontaneous mutations to become high-level constitutive beta lactamase producers, thus remaining resistant to most beta-lactam antibiotics. This has been the most common event at our medical center since 1986. Plasmid mediated beta-lactamases and bacterial cell membrane protein alterations also confer resistance, resulting in clinically important challenges. At the University of Iowa Hospitals and Clinics, beta-lactam-resistant Pseudomonas, Citrobacter, and Enterobacter were observed over a 2-year period, an event that correlated with the introduction of the "third-generation" cephalosporin ceftazidime to the formulary. As ceftazidime use increased from 1986 to 1988, the minimal inhibitory concentrations (MICs) for not only ceftazidime but also some other "third-generation" cephems increased for Pseudomonas aeruginosa. Similarly, susceptibility of Citrobacter spp. and Enterobacter spp. declined during this period for ceftazidime and, to a lesser extent, the unrelated broad-spectrum penicillin, piperacillin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737441 TI - Microbial resistance surveillance techniques. Blood culture versus multiple body site monitoring. AB - The continuing problem of nosocomial bacterial infections has resulted in the development of new techniques to monitor their prevalence and detect the emergence of drug resistance. "Focused microbial surveillance," in which bacterial incidence and antimicrobial susceptibilities are assessed by specific hospital units, provides unique information in the evaluation of emerging outbreaks of resistant Gram-negative pathogens. Within a given unit, however, pooled microbiologic data may be misleading, since they reflect only the average of multiple susceptibilities and may represent either colonization or infection. Formerly, at the University of Iowa Hospitals and Clinics, bacterial surveillance within a particular unit had typically been performed using blood-sample analysis, which was viewed as an effective index of the activity of most classes of antimicrobial agents. However, specific body site surveillance (wounds, sputum, urine, and so forth) may offer advantages over blood-culture analysis with some forms of resistance (or types of bacteria), such as stably derepressed type-I beta-lactamase production, which seems to develop rather quickly. Site specific surveillance may enable earlier detection of rapidly emerging resistant strains and the identification of virulent new serotypes or specific causes. Our data demonstrated that there is a greater probability of detecting resistant bacterial strains of Enterobacter colonizing and subsequently producing infections in the respiratory tract, urinary tract, or wound site. There was a time delay of almost 3 years between first observing resistant strains in sputum, urine, or pus and encountering them in an alarming incidence among blood cultures. Other studies confirm this particular phenomenon. In a survey of penicillin-resistant enterococci, the majority of clinical isolates were obtained from sites other than blood: seven from urine; five from wounds; two each from rectal swabs, ascitic fluid, and blood; and one each from a peritoneal catheter, Bartholin's cyst abscess, and pancreatic abscess. Effective techniques for selective surveillance should be both sensitive and cost effective. Current evidence suggests that site-specific monitoring (wounds, sputum, pleural effusions, urine, and feces) offers the advantages of more rapid identification of resistance trends prior to their appearance in the bloodstream cultures. PMID- 1737442 TI - Trends in antibiotic utilization and bacterial resistance. Report of the National Nosocomial Resistance Surveillance Group. AB - The increasing use of "third-generation" cephalosporins has been associated with a rising prevalence of resistant bacteria possessing type-I beta-lactamases. At Millard Fillmore Hospital (Buffalo, New York), we observed an unusually high occurrence of multiply resistant Enterobacter cloacae infections, especially in the intensive care unit. Susceptibilities were found to have declined substantially from 1988 to 1990, most notably for ceftazidime and mezlocillin, which decreased from 83% to 54% and from 85% to 64%, respectively. During the same period, there was a substantial increase in the use of ceftazidime and a decline in the use of the broad-spectrum penicillins. The latter drugs had been used in combination with an aminoglycoside as the primary empiric antibiotic therapy for nosocomial infections. This change in antibiotic-prescribing patterns was coincident with the decline in E. cloacae susceptibility, and therefore the emergence of multiply resistant E. cloacae was probably a direct consequence of the increased prescribing of ceftazidime. The experience at out institution led to the formation of the National Nosocomial Resistance Surveillance Group (NNRSG) to determine whether this antibiotic use-mediated resistance was a nationwide phenomenon. Clinical pharmacists and medical microbiologists were recruited and asked to complete a survey of hospital demographics, antibiotic purchases (between the beginning of 1988 and the third quarter of 1990), and bacterial susceptibilities of six representative organisms to 12 commonly used antibiotics (primarily broad-spectrum penicillins and cephalosporins). Evaluable data were obtained from 18 hospitals varying widely in bed capacity, antibiotic use, and geographic location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737443 TI - A review of traditional resistance surveillance methodologies and infection control. AB - The hospital affords an excellent environment for the proliferation of pathogenic bacteria and for the selection of antimicrobial-resistant strains. This article traces the evolution of microbiologic surveillance techniques and highlights some of the more effective means of infection control. Traditional surveillance methods relied on nationwide antimicrobial susceptibility data for practical information regarding the nature of infectious disease trends in order to guide the selection of appropriate empiric antibiotic therapy. The application of nationwide antibiograms to the local hospital setting may mask the local emergence of rapidly developing resistances, such as chromosomally mediated type I beta-lactamase resistance, which has been associated with increased use of certain cephalosporins. "Focused surveillance" techniques yield improved detection of emerging localized resistances within specific hospital units. In addition to unit-specific surveillance, many hospitals are now observing the advantages of an infection site-specific monitoring program. Judicious use of newer antimicrobials and implementation of detailed hospitalwide surveillance procedures will help to minimize the spread of epidemic and resistant infections. It remains the responsibility of the infection control and antibiotic utilization or advisory committees to make appropriate recommendations concerning the selection, restriction, and proper use of the newer extended-spectrum antibiotics. The clinical microbiology laboratory as a source of information remains a key participant in a quality program. PMID- 1737444 TI - Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta lactamase resistance. AB - The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737445 TI - Antibiotic resistance. Epidemiology and therapeutics. PMID- 1737446 TI - Trigeminal neuralgia. AB - Although the full and precise etiology of TN still awaits further elucidation, this extremely painful disorder can be treated successfully by a variety of techniques, pharmacologic and surgical, with minimal side effects. There is no excuse in the 1990's for patients with TN not to be diagnosed promptly and treated expeditiously and successfully. PMID- 1737447 TI - The psychosocial effects of ambiguous genitalia. PMID- 1737448 TI - General overview and treatment considerations of anorexia and bulimia. PMID- 1737449 TI - Practical aspects of the pharmacotherapy of headache. PMID- 1737450 TI - Leuko-araiosis: description and clinical correlates. AB - The term leuko-araiosis as predicted by Hachinski may now have outlived its usefulness. Careful delineation of the white matter changes seen in MR imaging by use of the MR characteristics and by the location of the lesions may reduce the apparent heterogeneity of the associate clinical and neuropathological findings. As currently defined, leuko-araiosis is seen in aggregate more commonly in subjects with cerebro-vascular disease or with cerebro-vascular risk factors but it is a common finding associated with aging in otherwise normal, healthy elderly subjects. Its clinical significance as an isolated finding in these populations should therefore be treated cautiously. Its appearance should alert the physician however to seek for and treat potential cerebro-vascular risk factors. PMID- 1737451 TI - Time to abandon routine albumin supplementation. PMID- 1737452 TI - Hand in glove. PMID- 1737453 TI - Effect of hypoalbuminemia and parenteral nutrition on free water excretion and electrolyte-free water resorption. AB - OBJECTIVE: To measure the effect of human albumin supplementation during parenteral nutrition on serum albumin concentrations, colloid oncotic pressure, free water clearance, electrolyte-free water resorption, and sodium excretion. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Thirty adult, hypoalbuminemic patients who required parenteral nutrition. INTERVENTIONS: Parenteral nutrition (control) or parenteral nutrition plus human albumin 25 g/L as a continuous infusion (treatment) for a 5-day study period. MEASUREMENTS: On days 1 and 5, serum albumin concentration, colloid oncotic pressure, free water clearance, electrolyte-free water resorption, and sodium excretion were measured. RESULTS: Serum albumin concentrations increased significantly from day 1 to day 5 in both groups (control: 2.0 +/- 0.1 [mean +/- SEM] vs. 2.3 +/- 0.1 g/dL [20 +/- 1 vs. 23 +/- 1 g/L], p = .02; treatment: 2.2 +/ 0.1 vs. 3.5 +/- 0.2 g/dL [22 +/- 1 vs. 35 +/- 2 g/L], p = .0001). Day 5 serum albumin concentrations were significantly higher in the treatment group compared with control (p = .0001). Colloid oncotic pressure increased significantly from day 1 to day 5 in the treatment group (17.8 +/- 0.8 vs. 25.1 +/- 1.0 mm Hg, p = .0001), and was significantly higher than control at day 5 (p = .0001). No significant differences were found for free water clearance, electrolyte-free water resorption, or sodium excretion within or between groups. CONCLUSIONS: In hypoalbuminemic patients, human albumin supplementation during parenteral nutrition results in significant increases in serum albumin concentrations and colloid oncotic pressure, but has no apparent effect on free water clearance, electrolyte-free water resorption, or sodium excretion. PMID- 1737454 TI - Anatomy of a defective barrier: sequential glove leak detection in a surgical and dental environment. AB - OBJECTIVES: a) To determine the frequency of perforations in latex surgical gloves before, during, and after surgical and dental procedures; b) to evaluate the topographical distribution of perforations in latex surgical gloves after surgical and dental procedures; and c) to validate methods of testing for latex surgical glove patency. DESIGN: Multitrial tests under in vitro conditions and a prospective sequential patient study using consecutive testing. SETTING: An outpatient dental clinic at a university dental school, the operating suite in a medical school affiliated with the Veteran's Hospital, and a biomechanics laboratory. PERSONNEL: Surgeons, scrub nurses, and dental technicians participating in 50 surgical and 50 dental procedures. METHODS: We collected 679 latex surgical gloves after surgical procedures and tested them for patency by using a water pressure test. We also employed an electronic glove leak detector before donning, after sequential time intervals, and upon termination of 47 surgical (sequential surgical), 50 dental (sequential dental), and in three orthopedic cases where double gloving was used. The electronic glove leak detector was validated by using electronic point-by-point surface probing, fluorescein dye diffusion, as well as detecting glove punctures made with a 27 gauge needle. RESULTS: The random study indicated a leak rate of 33.0% (224 out of 679) in latex surgical gloves; the sequential surgical study demonstrated patency in 203 out of 347 gloves (58.5%); the sequential dental study showed 34 leaks in the 106 gloves used (32.1%); and with double gloving, the leak rate decreased to 25.0% (13 of 52 gloves tested). While the allowable FDA defect rate for unused latex surgical gloves is 1.5%, we noted defect rates in unused gloves of 5.5% in the sequential surgical, 1.9% in the sequential dental, and 4.0% in our electronic glove leak detector validating study. In the sequential surgical study, 52% of the leaks had occurred by 75 mins, and in the sequential dental study, 75% of the leaks developed by 30 mins. In terms of the anatomical localization, the thumb and forefinger accounted for more than 60% of the defects. There were no differences in the frequency of glove leaks between the left and right hand. Leak rates were highest for the surgeon (52%), followed by the first assistant (29%) and the scrub nurse (25%). No false negatives were noted using the electronic glove leak detector; one false positive was seen out of 225 gloves tested (0.44%), as noted in our validation studies. CONCLUSIONS: Significantly high glove leak rates were noted after surgical and dental procedures, indicating that the present day latex surgical gloves can become an incompetent barrier once they are used. Unused latex surgical gloves demonstrated a higher rate of defects than allowed by the Food and Drug Administration standards, indicating substantial noncompliance of quality control standards by manufacturers as well as inadequate governmental oversight. Double gloving, or the use of thicker latex surgical gloves, would probably reduce the frequency of glove leaks. Latex surgical gloves should be tested for patency before use and during surgical and dental procedures. PMID- 1737455 TI - Complications of endotracheal intubation and mechanical ventilation in infants and children. AB - OBJECTIVE: To assess the frequency of complications of endotracheal intubation and mechanical ventilation. DESIGN: Prospective cohort study. SETTING: Pediatric tertiary multidisciplinary ICU. PATIENTS: Eight hundred sixty-nine serial patients, of whom 500 were endotracheally intubated and 431 were mechanically ventilated. INTERVENTIONS: Daily clinical observation. MAIN OUTCOME MEASURES: Age, diagnosis, endotracheal tube size, type of ventilator and humidification, duration of intubation and mechanical ventilation, ventilatory settings, and complications (accidental extubation, tissue damage, endobronchial intubation, postintubation stridor, endotracheal tube blockage, pulmonary airleak, bronchopulmonary dysplasia, pulmonary atelectasis) were recorded. RESULTS: The median patient age was 10 months (25th and 75th quartiles: 1 month and 15 yrs). The median duration of endotracheal intubation and mechanical ventilation was 4 days and 2 days, respectively. A total of 186 complications were recorded in 119 (24%) patients. No deaths were due to intubation or ventilation. The overall frequency of accidental extubation was 3.2% of patients at a rate of 1.26 extubations/100 intubation days. In nonventilated, unsedated patients with croup or epiglottitis, the frequency of accidental extubation was 23% at a rate of 11.83 extubations/100 intubation days. Lung atelectasis occurred in 7.8%, airleak in 6.8%, and infection in 2.3% of patients. Other complications included tissue damage (3.4%), endobronchial intubation (2.4%), postintubation stridor (2.4%), bronchopulmonary dysplasia (2.3%), and endobronchial tube blockage (0.8%). CONCLUSIONS: Complications were related to the duration of intubation and mechanical ventilation. PMID- 1737456 TI - Hormonal responses to trauma. AB - OBJECTIVES: To review the hormonal changes that have been reported after trauma, to define their etiologies, and to describe their consequences. DATA SOURCES: Literature review using MEDLINE and original data. DATA SYNTHESIS: Hormonal responses to trauma are bidirectional. Functional derangements include increases in adrenocorticotropin hormone and cortisol, growth hormone, and prolactin levels. In contrast, gonadotropin and gonadal steroid, and thyroid hormone concentrations decrease. The response is immediate but not necessarily sustained for those hormones that respond with increased secretion, whereas the effect may not become apparent for several hours, may be maximal after 1 to 4 days, and may persist for the duration of illness for those hormones that decrease. The reduction in hormone concentrations generally reflect diminished secretion, with the exception of the thyroid hormones where altered metabolic pathways and enhanced metabolic clearance play a major role. CONCLUSIONS: The changes in circulating levels do not appear to be injury specific, but tend to reflect the severity of the traumatic insult, and there are some data for cortisol and thyroxine that show their concentrations may be of predictive value. In head injured patients, structural as well as functional pituitary changes may be present. Patients may show varying degrees of pituitary insufficiency. However, the presence of hyperprolactinemia strongly suggests involvement of the hypothalamus. With the exception of bonafide hypopituitarism, the relevance of the hormonal changes after trauma awaits clarification. PMID- 1737457 TI - Chloride ion in intensive care medicine. AB - OBJECTIVE: To review the physiology of the chloride ion and its relationship to various disease states encountered in the ICU. Special emphasis was paid to the renal handling of chloride and its role in the evaluation of the urine and serum anion gaps. Metabolic acidosis and alkalosis are discussed. DATA SOURCES: English language articles were identified through a search of the MEDLINE and Index Medicus databases. Bibliographies of retrieved articles were examined for relevant articles. STUDY SELECTION: Approximately 125 articles and 25 textbook chapters were reviewed. Those articles most applicable to the ICU were used. Information contained in text chapters was included primarily in the tables. DATA EXTRACTION: All available information was reviewed and analyzed by the authors before inclusion. DATA SYNTHESIS: Guidelines for the evaluation of urine and serum electrolyte concentrations are presented. The use of the urine anion gap is discussed, particularly as it relates to the diagnosis of hyperchloremic metabolic acidosis. Stool chloride provides information relevant to congenital and acquired diarrheas. The evaluation of metabolic acidosis requires the calculation of the serum anion gap. Both normal and increased gap acidoses are discussed, although increased gap acidoses are more commonly encountered in the ICU. Urine chloride is invaluable in defining whether the metabolic alkalosis is sodium-chloride responsive (urine chloride less than 10 mmol/L) or sodium chloride-unresponsive (urine chloride greater than 20 mmol/L). CONCLUSIONS: Measurement of chloride is a valuable tool in the evaluation and treatment of a variety of disorders. Serum chloride is most helpful in assessing both normal and increased anion gap metabolic acidoses, while urine chloride finds utility in the diagnosis of metabolic alkalosis and hyperchloremia metabolic acidosis. The evaluation of any disturbance in chloride homeostasis that defies easy explanation necessitates the measurement of stool electrolytes. PMID- 1737458 TI - Electrolyte abnormalities in critically ill children. AB - OBJECTIVE: To provide a brief overview of the causes, diagnosis, and therapies of electrolyte abnormalities frequently seen in critically ill children. DATA SOURCE: Published articles and bibliographies identified from pertinent review articles and books published in the past 20 yrs on fluid and electrolyte therapy in children. CONSTRAINT: The review includes only human studies and articles published in the English language. STUDY SELECTION: Human studies pertaining to abnormalities of water homeostasis, sodium, potassium, calcium, and magnesium homeostasis in children were selected. Prospective randomized studies were selected as much as possible. DATA EXTRACTION: Pertinent data abstracted from multiple, independent clinical studies were used to develop an approach to electrolyte abnormalities in critically ill children. DATA SYNTHESIS: An approach to diagnosis and therapies of common electrolyte abnormalities in critically ill children. CONCLUSIONS: Electrolyte abnormalities are common in critically ill children and can be easily treated once recognized. Further studies are needed to better understand the role of ionized calcium and magnesium in neonatal and pediatric critical illness. PMID- 1737459 TI - Hypocalcemia in critically ill patients. AB - PURPOSE: To review calcium regulation, causes of hypocalcemia during critical illness, clinical features and treatment of hypocalcemia, hemodynamic effects of calcium administration, calcium-catecholamine interactions, and the role of calcium in ischemic injury. DESIGN: Representative articles from the medical literature are used to support the discussion of selected aspects of calcium metabolism which are important to the practice of critical care medicine. SUBJECTS: Results from both animal and human investigations and both in vitro and in vivo studies are discussed. RESULTS: Circulating calcium levels are best measured using ionized calcium electrodes. Ionized hypocalcemia is common in critically ill patients and usually results from impaired parathyroid hormone secretion or action, impaired vitamin D synthesis or action, or calcium chelation/precipitation. Ionized hypocalcemia most commonly presents as cardiovascular or neuromuscular insufficiency. Mild ionized hypocalcemia (greater than 0.8 mmol/L) is usually asymptomatic and frequently does not require treatment. Moderate-to-severe ionized hypocalcemia is best treated with iv calcium in the critically ill patient. The majority of studies report no increase in cardiac output but a significant increase in BP after iv calcium administration. When administered with beta-adrenergic agonists, calcium frequently impairs their cardiovascular actions. Intracellular calcium dysregulation is common during ischemic and shock states. Agents which increase intracellular calcium may be harmful during cellular ischemia. CONCLUSIONS: Alterations in calcium regulation and calcium concentrations are common during critical illness. Optimal management of altered calcium concentrations requires an understanding of the pathophysiology behind these alterations. PMID- 1737460 TI - Magnesium-adenosine triphosphate in the treatment of shock, ischemia, and sepsis. AB - PURPOSE: To review the rationale for adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration in shock, ischemia, and sepsis; the beneficial effects on cellular and organ functions and survival; and possible mechanisms of these effects. DATA SOURCES: Current literature review. STUDY SELECTION: Articles deemed most pertinent, current, and representative were utilized. DATA SYNTHESIS: Despite apparent, adequate resuscitation of hypovolemic shock and sepsis in experimental animals and patients, persistent cellular and organ dysfunction is apparent. Disturbances in organ microcirculation and tissue hypoxia appear to play an important role. These disturbances occur when the energy needs are increased. Because of the theoretical benefits of ATP-MgCl2 as an energy source, as well as a vasodilator, the administration of ATP-MgCl2 has been investigated extensively, and considerable evidence suggests that ATP-MgCl2 restores the depressed cell and organ functions following ischemia, hypovolemic shock, and sepsis. CONCLUSIONS: ATP-MgCl2 improves cellular and organ function and survival following experimental shock, ischemia, and sepsis. Studies also indicate that ATP-MgCl2 can be administered safely in experimental animals and in normal human volunteers, as well as in patients following various adverse circulatory conditions. Further trials should be undertaken to determine the effects on cell and organ function in patients following traumatic shock and sepsis. PMID- 1737461 TI - Metabolic and anatomic thyroid emergencies: a review. AB - PURPOSE: To review the diagnosis and management of thyroid diseases, both metabolic (thyroid storm and myxedema coma) and anatomic (substernal goiter, lymphoma, anaplastic carcinoma) that may require intensive care therapy. DATA SOURCES: English-language articles were identified through a search of the MEDLINE and Index Medicus databases. Bibliographies of retrieved articles were examined for relevant articles. STUDY SELECTION: Approximately 250 articles were reviewed. Those articles deemed most representative were utilized. Case reports were included to highlight rare, but potentially lethal complications. DATA EXTRACTION: All data were analyzed by one observer. Limitations of the data are discussed. DATA SYNTHESIS: Guidelines for determining the etiology of thyrotoxic crisis are outlined. Criteria for distinguishing critically ill hypothyroid patients from those patients with the euthyroid sick syndrome are given. Therapy for both disorders must be aggressive and multifaceted, and detailed management is indicated. Substernal goiter is almost always benign, but may cause various acute complications, including dyspnea, respiratory failure, superior vena caval syndrome, esophageal varices (downhill), and others. Surgery almost always corrects the problem. Lymphomas present with rapid thyroid enlargement. Recent studies suggest that surgery may assume more of a supportive role, used principally to obtain adequate tissue for histologic classification. CONCLUSIONS: Thyroid disorders can produce emergencies requiring the attention of multiple medical and surgical specialists. While management is often successful, future studies should address the following three areas: a) optimization of thyroid hormone dose for treatment of myxedema coma; b) clarification of the role of radiotherapy and/or chemotherapy for thyroid lymphoma; and c) more effective therapy for anaplastic carcinoma. PMID- 1737462 TI - An evaluation of the physical and functional characteristics of resuscitators for use in pediatrics. AB - OBJECTIVE: To evaluate the physical and functional characteristics of pediatric self-inflating resuscitators. DESIGN: Tested under simulated clinical conditions. Results were analyzed by descriptive analysis. SETTING: A pulmonary laboratory in a university hospital. METHODS: Eight new pediatric self-inflating resuscitators were obtained from the manufacturers and evaluated for functional characteristics including: a) fraction of delivered oxygen at 10 L/min and a tidal volume of 300 mL; b) maximum stroke volume against no resistance; and c) maximum cycling frequency at -5 degrees C, 20 degrees C, and 48 degrees C. The resuscitators were also evaluated for physical characteristics, including potential for misassembly, pressure relief valves, expiratory valve leak, and inspiratory resistance. RESULTS: All resuscitators met the minimum standards of the Canadian Standards Association and American Standards for Testing of Materials. However, one bag cycled at only 32 breaths/min at -5 degrees C, marginally within accepted standards. Only five self-inflating resuscitators had pop-off valves. These valves malfunctioned, with valve activation occurring well above the accepted standards. Three of the self-inflating resuscitators could be misassembled for use. Four of the resuscitators were unable to deliver tidal volumes required for preoxygenation in a 20-kg child. CONCLUSIONS: While these self-inflating resuscitators met the minimum standards, they are all unable to deliver 100% oxygen. One unit is probably not appropriate in the out-of-hospital setting when ambient temperatures are less than 0 degrees C. Those resuscitators that can be misassembled are dangerous in unskilled hands. In addition, reliance on pop-off valve activation to limit airway pressure is dangerous. PMID- 1737463 TI - Effect of increased intra-aortic balloon pressure on catheter volume: relationship to changing altitudes. AB - OBJECTIVE: To evaluate the effect of intra-aortic balloon membrane response under increasing intracatheter pressure by indexing these data to associated barometric pressures that occur with changes in altitude. DESIGN: A static compliance test was performed to assess the effect of internal pressure on intra-aortic balloon compliance (simulating helium gas within the intra-aortic balloon affected by barometric pressure). Testing consisted of incrementally increasing pressure within eight percutaneous intra-aortic balloons from four leading manufacturers. SETTING: The University of Utah Department of Mechanical Engineering Laboratory. PATIENTS: No patients were involved. This study was a bench test lab study. INTERVENTIONS: No patient interventions were utilized. RESULTS: Results for all trials showed a curvilinear relationship between intracatheter pressure and balloon volume. Clinically significant balloon expansion data were obtained, with manufacturer variation observed at moderate-to-high pressures. CONCLUSIONS: Based on the results of this study, recommendations for operation of intra-aortic balloon pumps during altitude ascent and descent are proposed, from which individual institutional protocols may be developed. PMID- 1737464 TI - Midazolam-induced angioedema and bronchoconstriction. PMID- 1737465 TI - Shortcomings of acute physiology and chronic health evaluation II. PMID- 1737466 TI - Small-bore feeding tubes. PMID- 1737467 TI - Guidelines for care: a surgical perspective. PMID- 1737468 TI - Order of markers on chromosome 21. PMID- 1737469 TI - A Bayesian analysis for mapping from radiation hybrid data. PMID- 1737470 TI - Physical mapping by multiple pairwise analysis. PMID- 1737471 TI - A statistical and numerical view of the chromosome 21 physical map data. PMID- 1737472 TI - An application of empirical Bayes methods to updating linkage information on chromosome 21. PMID- 1737473 TI - Mapping of chromosome 21 markers in the Venezuelan pedigree. PMID- 1737474 TI - Using recombinant chromosomes to map new markers. PMID- 1737475 TI - Multilocus mapping strategies on chromosome 21 data sets: comparison of results from family data, radiation hybrids, and somatic cell hybrids. PMID- 1737476 TI - Construction and comparison of chromosome 21 radiation hybrid and linkage maps using CRI-MAP. PMID- 1737477 TI - Preliminary ranking procedures for multilocus ordering based on radiation hybrid data. PMID- 1737478 TI - Disequilibrium on chromosome 21 in some Utah families. PMID- 1737479 TI - Genetic Analysis Workshop 7: recent progress in statistical methods. PMID- 1737480 TI - A novel pedigree plotting algorithm. PMID- 1737481 TI - Compilation for fast calculation over pedigrees. PMID- 1737482 TI - ELODs for three loci. PMID- 1737483 TI - A multisample bootstrap approach to the estimation of maximized-over-models lod score distributions. PMID- 1737484 TI - Linkage analysis of two-locus diseases under single-locus and two-locus analysis models. PMID- 1737485 TI - Genetic Analysis Workshop 7: summary of the melanoma workshop. PMID- 1737486 TI - Description of the National Cancer Institute melanoma families. PMID- 1737487 TI - The Dutch FAMMM family material: clinical and genetic data. PMID- 1737488 TI - The study of nevi in British twins: study design and description of the data set. PMID- 1737489 TI - Number, size, and histopathology of nevi in Utah kindreds. PMID- 1737490 TI - Clinical aspects of hereditary melanoma in Australia. PMID- 1737491 TI - Preliminary evaluation of linkage between chromosome 1p markers and nevus densities in the Utah data. PMID- 1737492 TI - Sib-pair linkage analysis applied to pedigrees with melanoma and dysplastic nevi. PMID- 1737493 TI - Multivariate genetic analysis of nevus measurements and melanoma. PMID- 1737494 TI - Linkage analysis of malignant melanoma with the chromosome 1 markers D1S47 and PND. PMID- 1737495 TI - Analysis of nevus count data from twins. PMID- 1737496 TI - Genetic relationship between nevus count or nevus density and cutaneous malignant melanoma. PMID- 1737497 TI - Regressive logistic models in linkage analysis of the cutaneous malignant melanoma-dysplastic nevus syndrome. PMID- 1737498 TI - Is the genetics of moliness simply the genetics of sun exposure? A path analysis of nevus counts and risk factors in British twins. PMID- 1737499 TI - Segregation analysis of total nevus density and estimation of lifetime risk and average onset age of melanoma. PMID- 1737500 TI - Inheritance of nevus number and size in melanoma/DNS kindreds. PMID- 1737501 TI - Linkage analysis of melanoma alone and chromosome 1p markers PND, D1S47, and LMYC. PMID- 1737502 TI - Genetic linkage and affected pedigree member analysis in malignant melanoma. PMID- 1737503 TI - Linkage analysis with adjustment for covariates: a method combining peeling with Gibbs sampling. PMID- 1737504 TI - Multivariate analysis of nevus counts in twins. PMID- 1737505 TI - Genetic analysis of cutaneous melanoma and dysplastic nevi under varying phenotypic definitions. PMID- 1737506 TI - Genetic analysis of nevus density in melanoma families. PMID- 1737507 TI - Estimated power to detect linkage in three CM/DN data sets. PMID- 1737508 TI - Investigation of major gene and covariate effects using a new Poisson process model. PMID- 1737509 TI - Segregation analysis in cutaneous malignant melanoma/dysplastic nevus syndrome families. PMID- 1737510 TI - Fitting genetic data using Gibbs sampling: an application to nevus counts in 38 Utah kindreds. PMID- 1737512 TI - Genetic Analysis Workshop 7: issues in gene mapping and detection of major genes. Dayton, Ohio, October 14-16, 1990. PMID- 1737511 TI - PEDSCORE analysis of identical by descent (IBD) marker allele distributions among family members with cutaneous melanoma. PMID- 1737513 TI - Genetic Analysis Workshop 7: radiation hybrid and somatic cell hybrid mapping of chromosome 21. PMID- 1737514 TI - Genetic Analysis Workshop 7: mapping chromosome 21 linkage markers. PMID- 1737515 TI - Radiation hybrid mapping. PMID- 1737516 TI - The role of somatic cell hybrids in physical mapping. PMID- 1737517 TI - Chromosome 21 genetic linkage data set based on CEPH pedigrees. PMID- 1737518 TI - The gene order problem when using somatic cell hybrids. PMID- 1737519 TI - Comparisons of radiation hybrid mapping and linkage mapping. PMID- 1737520 TI - Radiation hybrid mapping by minimization of the number of obligate chromosome breaks. PMID- 1737521 TI - A theory for radiation hybrid (Goss-Harris) mapping: application to proximal 21q markers. PMID- 1737522 TI - Accepting parental responsibility: "future questioning" as a means to avoid foster home placement of children. PMID- 1737523 TI - The impact of family structure on the adjustment of adopted children. AB - Psychological and academic adjustments were assessed in a group of 130 adopted children (six to 12 years of age) living in five different family constellations: only children, children with younger adopted siblings only, children with younger biological siblings only, children with older adopted siblings only, and children with older biological siblings only. Few differences were found from one cluster to another, suggesting that family structure, while complicating the dynamics of adoptive family life, plays a minor role in adoption adjustment. PMID- 1737524 TI - The Family Connection Center: an innovative visiting program. AB - Child-family visiting in out-of-home care is at the heart of determining whether the family will be reunified or other permanency plans will be made. A purchase of-service arrangement enables a voluntary agency to carry a portion of the visiting process for a public agency in a coordinated operation. A separately funded unit of the voluntary agency offers a visiting service for children of divorce whose parents are at serious odds with each other. PMID- 1737525 TI - Glutathione infusion potentiates glucose-induced insulin secretion in aged patients with impaired glucose tolerance. AB - OBJECTIVE: To evaluate the effect of glutathione infusion on beta-cell response to glucose in elderly people with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Ten patients with normal glucose tolerance and 10 patients with IGT were matched for age (mean +/- SE, 72.1 +/- 2.8 vs. 71.0 +/- 3.4 yr), body mass index (23.1 +/- 1.1 vs. 22 +/- 2.1 kg/m2), and sex (6/4 vs. 5/5, men/women) underwent glutathione infusion (10 mg/min) under basal conditions and during 75-g oral glucose tolerance tests and intravenous glucose tolerance tests (0.33 g.kg body wt-1.3 min-1). Patients with IGT were also submitted to euglycemic-hyperinsulemic and hyperglycemic glucose clamps. RESULTS: In subjects with normal glucose tolerance, glutathione infusion failed to affect beta-cell response to glucose. In contrast, glutathione significantly potentiated glucose induced insulin secretion in patients with IGT. Furthermore, in the latter group studied by hyperglycemic clamps, glutathione infusion significantly potentiated the beta-cell response to glucose when plasma glucose levels varied between 10 and 15 mM. This effect disappeared at plasma glucose levels greater than 15 mM. No effect of glutathione on insulin clearance and action was observed. CONCLUSIONS: Glutathione infusion enhances insulin secretion in elderly people with IGT. PMID- 1737526 TI - Care of diabetic pregnant women by primary-care physicians. Reported strategies for managing pregestational and gestational diabetes. AB - OBJECTIVE: To ascertain the strategies used by primary-care physicians for treating pregestational and gestational diabetes mellitus (GDM) during pregnancy, because many women with pregnancies complicated by these types of diabetes are treated by physicians who have no special training in intensive diabetes management. RESEARCH DESIGN AND METHODS: Two hundred twenty-four family-practice (FP) physicians and 184 obstetrics/gynecology (OB/GYN) physicians were surveyed by mail. RESULTS: When compared with OB/GYNs, FPs were less likely to screen all pregnant women for GDM (P = 0.03), use multiple-injection insulin regimens (P = 0.004) or self-monitoring of blood glucose (SMBG) (P = 0.01) for Pre-GDM patients, and refer these patients to a specialist for medical (P = 0.01) or ophthalmologic (P less than 0.001) care. FPs were more likely to implement insulin therapy (P = 0.003), SMBG (P = 0.02), and examine eyes for retinopathy (P less than 0.001) when treating gestational patients. CONCLUSIONS: These data show that there are considerable discrepancies between the strategies used by FPs and OB/GYNs and also suggest that physicians in both groups are under-utilizing recommended treatment strategies described in publications targeted specifically to primary-care physicians. Increased exposure to and dissemination of guidelines for diabetes management and additional medical school and postgraduate education programs are recommended as methods to improve utilization of these strategies. PMID- 1737527 TI - Accuracy of a filter paper method for measuring glycosylated hemoglobin. AB - OBJECTIVE: To compare glycosylated hemoglobin (GH) results obtained by filter paper fingerstick collection and mailed for assay by affinity chromatography with results from a venous sample assayed by ion-exchange chromatography (HbA1) in a local laboratory. RESEARCH DESIGN AND METHODS: Fifty-eight volunteer subjects with insulin-dependent diabetes mellitus (IDDM), aged 5-24 yr, included patients at a referral-based IDDM clinic and subjects in an ongoing research study. We obtained two blood samples from each subject. One was collected by fingerstick onto filter paper, the other by venipuncture into a vacutainer. We sent filter paper samples to the Diabetes Research Laboratory (Univ. of Missouri, Columbia, MO) for analysis. Vacutainer samples were sent to the Clinical Chemistry Department of the Clinical Laboratory, University of Colorado Health Sciences Center. RESULTS: Results were highly correlated (r = 0.89, P = 0.0001). Fifty nine percent were classified identically when results were normalized to SD units and grouped to suggest levels of clinical concern. CONCLUSIONS: The filter paper method is a convenient, accurate measure of glycosylated hemoglobin in young people with IDDM. It should be considered a credible alternative research and clinical tool. PMID- 1737528 TI - Prevalence of diabetes and impaired glucose tolerance among Navajo Indians. AB - OBJECTIVE: To estimate the prevalence of diabetes mellitus and impaired glucose tolerance and the incidence of clinically diagnosed diabetes in a community of Navajo Indians. RESEARCH DESIGN AND METHODS: We conducted a survey of a representative Navajo community screened for diabetes 3 yr previously. We used 75 g oral glucose tolerance tests to determine the prevalence of diabetes mellitus and impaired glucose tolerance and conducted medical record reviews to identify cases of diabetes that were diagnosed during routine medical care after the earlier study. RESULTS: By World Health Organization diagnostic criteria, the age adjusted diabetes prevalence among 419 Navajo Indians 20-74 yr of age was 13.9% (95% confidence interval [CI] 9.2-18.5) for men and 18.4% (95% CI 14-22.8) for women. The ratio of the prevalence of diabetes among the Navajo population studied to that in the general United States population was 2.5. The prevalence of impaired glucose tolerance was 8% (95% CI 3.3-12.7) among men and 12.9% (95% CI 7.9-17.9) among women. Based on clinical diagnoses of diabetes made during routine medical care, mean +/- SE age-adjusted incidence of diagnosed diabetes among men was 8.6 +/- 4.3/1000 person-yr and 11.1 +/- 4.4/1000 person-yr among women. CONCLUSIONS: Although lower than that of some other tribes, the prevalence of diabetes among Navajo Indians is substantially higher than that in the general U.S. population. The high rate of clinical diagnoses suggests that the prevalence of the disease may continue to rise. PMID- 1737529 TI - Effects of human insulin on insulin binding antibody production in nondiabetic subjects. AB - OBJECTIVE: To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production. RESEARCH DESIGN AND METHODS: Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone. RESULTS: Mean +/- SE basal insulin antibody levels (1.2 +/- 0.2 micrograms/L) increased to a maximal level of 4.5 +/ 0.8 micrograms/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 +/- 0.3 micrograms/L. This represented a highly significant overall increase (P less than 0.001). A control group of six insulin dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 +/- 0.7-2.7 +/- 0.6 micrograms/L). CONCLUSIONS: These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy. PMID- 1737530 TI - Odyssey. PMID- 1737531 TI - Magic bullets, reportable disease, and prevention of childhood diabetes. PMID- 1737532 TI - Glutamate decarboxylase: an autoantigen in IDDM. PMID- 1737533 TI - Exercise in NIDDM may be a prescription for protection. PMID- 1737534 TI - New clues to IDDMs origins. PMID- 1737535 TI - Community-based retinopathy clinics. PMID- 1737536 TI - Effect of gemfibrozil on intermediate-density lipoproteins in NIDDM patients. A retrospective study. PMID- 1737537 TI - Topical capsaicin in painful diabetic neuropathy. Effect on sensory function. AB - OBJECTIVE: To examine the effect of capsaicin on sensory function in painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: We examined the effects of topical 0.075% capsaicin cream on thermal and vibration thresholds in 22 subjects with painful diabetic neuropathy who participated in a double-blind vehicle controlled therapeutic trial. RESULTS: After 8 wk of use, there was no significant change in warm and vibration thresholds, but the cold threshold was significantly reduced by capsaicin and vehicle creams to an equal degree. In fewer subjects who used capsaicin cream in an open-label study, there was no significant effect on sensory thresholds after up to 32 wk of use. CONCLUSIONS: Although our results and those of others show no adverse effects of topical 0.075% capsaicin on human sensory function, even in subjects with preexisting neuropathic sensory impairment, the small number of subjects tested does not justify an inferential statement on safety. Further studies in more subjects are warranted to ensure the long-term safety of capsaicin for pain relief in humans. PMID- 1737538 TI - Normalization of composition of triglyceride-rich lipoprotein subfractions in diabetic subjects during insulin infusion with programmable implantable medication system. AB - OBJECTIVE: To investigate whether long-term improved glycemic control by intraperitoneal insulin infusion normalizes the compositional abnormalities of triglyceride (TG)-rich lipoproteins in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Seven subjects were studied before and 12-14 mo after initiation of treatment with the programmable implantable medication system (PIMS). Plasma TG levels were measured, and the composition of three TG rich lipoprotein subfractions (Svedberg flotation [Sf] greater than 400, 100-400, and 20-100) were analyzed before and every 1.5 for 7.5 h after ingestion of corn oil. RESULTS: PIMS significantly improved glycemic control, as measured by mean blood glucose (P less than 0.02), and HbA1 (P less than 0.001, paired t test) levels. Weight loss was also observed during PIMS treatment. Significant changes occurred in the composition of TG-rich lipoprotein subfractions during PIMS treatment in both the fasting (P less than 0.002) and the postprandial (P less than 0.0001) state. Most changes were in the direction of nondiabetic values. PIMS treatment reduced the total cholesterol enrichment in IDDM subjects in all three subfractions in the postprandial state and the very-low-density lipoprotein subfractions (Sf 100-400 and 20-100) in the fasting state. Multivariate analysis showed that the compositional changes were affected by improved glycemic control, as assessed by both mean blood glucose and HbA1, whereas the very-low-density lipoprotein compositional changes were by both the improved glycemic control and body weight. CONCLUSIONS: In IDDM subjects during PIMS treatment, there was normalization of most abnormalities in the composition of fasting and postprandial TG-rich lipoproteins, including enrichment in total cholesterol, which is considered atherogenic. PMID- 1737539 TI - Effect of conventional and intensified insulin therapy on free-insulin profiles and glycemic control in NIDDM. AB - OBJECTIVE: To investigate the effects on 24-h insulin and glucose profiles of two and four-dose insulin regimens in patients with non-insulin-dependent diabetes mellitus (NIDDM) who have failed oral agent therapy. RESEARCH DESIGN AND METHODS: Ten patients with NIDDM and 10 matched nondiabetic control subjects took part in the study, a randomized crossover trial with 8-wk treatment periods. We determined 24-h profiles of blood glucose and free insulin in control subjects and patients when they were taking oral agents and at the end of each treatment period. The two-dose regimen was mixed (15% regular, 85% NPH) insulin given before breakfast and dinner, and the four-dose regimen was regular insulin given before meals and NPH given at 2200. RESULTS: Patients taking oral agents had higher mean blood glucose than control subjects (mean +/- SE 12.6 +/- 0.6 vs. 4.5 +/- 0.1 mM, P less than 0.0001) and similar 24-h insulin concentrations but lower postprandial insulin concentrations (at breakfast, 87.6 +/- 13.8 vs. 228.6 +/- 29.4 pM, P less than 0.01). Mean 24-h insulin concentrations were the same on two and four-dose regimens, and both regimens caused basal hyperinsulinemia. Glycemic control also improved. Postprandial insulin peaks were higher at lunch and dinner on the four-dose regimen, and postprandial blood glucose was lower. Fasting proinsulin was elevated in patients compared with the control subjects (25.1 +/- 4.7 pM vs. 5.0 +/- 0.9 pM, P less than 0.001) and was suppressed to normal during insulin treatment. CONCLUSIONS: Two- and four-dose insulin regimens can achieve similar glycemic control. Both regimens cause basal hyperinsulinemia but normalize the hyperproinsulinemia observed during failure of oral agent therapy. Four-dose insulin regimens offer few advantages to the glycemic control achieved with two-dose regimens but may be more physiological. PMID- 1737540 TI - Lipid status after pancreas-kidney transplantation. AB - OBJECTIVE: This study was performed to determine the net effects of euglycemia, resolution of renal failure, immunosuppressant drugs, and hyperinsulinemia on fasting lipid profiles of patients with renal failure and insulin-dependent diabetes mellitus (IDDM) after combined pancreas-kidney transplantation (PKT). RESEARCH DESIGN AND METHODS: Thirty subjects with IDDM received PKT between April 1989 and October 1990, and all were studied. Mean +/- SE age was 35.2 +/- 1.3 yr; 19 recipients were men, and 11 were women. All had a functioning pancreatic allograft post-PKT. Fasting lipid profiles including total cholesterol (C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-chol), and C/HDL chol were compared before and after PKT (38-555 days divided into groups: preoperation and 0-2, 3-8, and 9-19 mo). RESULTS: Significant hyperlipidemia was observed preoperatively (means +/- SE): C, 5.92 +/- 0.27 mM; HDL-chol, 1.07 +/- 0.09 mM; TG, 5.85 +/- 0.56 mM; and C/HDL-chol, 6.49 +/- 0.83. All lipids and C/HDL-chol dropped immediately after PKT (0-2 mo vs. preoperation, all P less than 0.01, except HDL-chol). After this immediate postoperative period, C, HDL chol, and TG stabilized at new concentrations. C (5.44 +/- 0.22 mM) and TG (4.54 +/- 0.48 mM) levels were less than preoperation (not statistically significant and P less than 0.05, respectively). HDL-chol was greater than preoperative values (1.29 +/- 0.06 mM, P less than 0.05). C/HDL-chol dropped after PKT (0-2 mo, 4.85 +/- 0.18, P less than 0.01) and continued to decrease throughout the observation period (3-8 mo, 4.42 +/- 0.23; 9-19 mo, 4.23 +/- 0.23; both P less than 0.01 vs. preoperation). There was no statistical difference between lipid concentrations in male and female subjects. CONCLUSIONS: The lipid status of subjects with IDDM and renal failure was abnormal before PKT and once lipid concentrations stabilized after PKT (greater than 2 mo), HDL-chol was higher and TG and C/HDL-chol levels were significantly lower than preoperative values. If these changes are sustained, risk of future cardiovascular disease in this group of patients might be significantly reduced. PMID- 1737541 TI - Parental and professional estimates of self-care independence of children and adolescents with IDDM. AB - OBJECTIVE: To report the results of a survey of 490 parents of children with insulin-dependent diabetes mellitus (IDDM) regarding the children's mastery of 38 diabetes-care skills. Parental responses are contrasted with those of a previous survey in which 229 diabetes professionals estimated ages at which typical children with IDDM master the same skills. RESEARCH DESIGN AND METHODS: Parents were recruited at five pediatric endocrinology clinics with a response rate of 88.9%. RESULTS: For 33 of 38 skills, professionals' median mastery age estimates exceeded, by greater than or equal to 1 yr, the median ages that parents reported skill mastery by their estimates, children. Despite the parent-professional disagreement about mastery-age their survey responses yielded substantial agreement about the order of mastery of specific skills. The data also revealed two profiles of comparative results. For many items, parents reported earlier skill mastery, but parental and professional estimates eventually converged during adolescence. These skills consisted of rote, motoric acts, or more complex tasks for which errors yield relatively certain aversive consequences. For other skills, more professional estimated skill mastery among adolescents than did parents. These skills required substantial organization and self-regulation by the adolescent, involved treatment components for which the aversive consequences of errors are deferred and uncertain, or they were skills infrequently required of most patients with IDDM. CONCLUSIONS: The parent-professional discordance revealed by this survey illustrates the importance of clear specification of treatment responsibilities, careful monitoring of self-care competence, and periodic reeducation of children with IDDM. PMID- 1737542 TI - Randomized comparison of metabolic control achieved by intraperitoneal insulin infusion with implantable pumps versus intensive subcutaneous insulin therapy in type I diabetic patients. AB - OBJECTIVE: To compare intraperitoneal implantable insulin infusion (IP) to subcutaneous (SC) intensive insulin therapy. RESEARCH DESIGN AND METHODS: Twenty one insulin-dependent (type I) diabetic patients aged 24-61 yr underwent a 3-mo treatment optimization using multiple SC daily injections or external pumps. Patients were then randomized (time 0 mo) to IP infusion using Infusaid programmable pumps or continuation on SC intensive insulin for 6 mo. RESULTS: No differences were noted between study and control group data. However, longitudinal within-group comparisons from baseline showed that glycosylated hemoglobin improved to near-normal in both groups: IP, 9.0 +/- 0.5 vs. 7.8 +/- 0.6% (P less than 0.05) and SC, 8.4 +/- 0.5 vs. 7.5 +/- 0.3% (P less than 0.5) at 0 and 4 mo, respectively (normal less than 6.9%). The percentage of blood glucose tests greater than 11 mM at 0 and 6 mo was 28 +/- 5 vs. 16 +/- 4% in the IP group (P less than 0.05) and 22 +/- 5 vs. 24 +/- 7% in the SC group (NS). At 0 and 6 mo, the standard deviation of blood glucose values, an index of glycemic fluctuations, was 4.3 +/- 0.4 vs. 3.2 +/- 0.5 mM in the IP group (P less than 0.05) and 3.7 +/- 0.3 vs. 4.0 +/- 0.4 mM in the SC group (NS). Weight, insulin dosages, circulating lipid levels, and the frequency of severe hypoglycemic reactions and biochemical hypoglycemias were similar and did not change in the two groups. CONCLUSIONS: IP-implantable pumps compared with SC intensive insulin therapy have similar effects on most metabolic variables and are equally effective at achieving near-normal glycemic levels. Only longitudinal data suggest that IP treatment may be more effective at limiting glycemic fluctuations. PMID- 1737543 TI - Natural course of remission in IDDM during 1st yr after diagnosis. AB - OBJECTIVE: To describe the natural course of clinical remission in insulin dependent diabetes mellitus (IDDM) when insulin dose is minimized without loss of target glycemia and to identify factors that predict clinical remission. RESEARCH DESIGN AND METHODS: Ninety-five patients, who were placebo-treated control subjects in the Canadian-European multicenter randomized trial of cyclosporin A in recent-onset IDDM, were studied. RESULTS: The mean insulin dose decreased during the first months after diagnosis, with a nadir at 3 mo, when 27% of the patients did not require insulin to maintain target glycemia. At 1 yr, 10% of patients still did not need insulin. Patients not receiving insulin who had glycosylated hemoglobin within the normal range were called remitters. Mean basal and glucagon-stimulated C-peptide values were significantly (P less than 0.025) higher in remitters than nonremitters at the start of the study. Therefore, all patients were divided into those with values above the mean stimulated C-peptide (0.4 nM) and those with values below the mean at entry. The probability of entering a remission with a stimulated C-peptide greater than 0.4 nM was 10 times as high (P less than 0.05) as for those with a stimulated C-peptide below this level. Surprisingly, the beginning and end of the remission were associated with neither major changes in C-peptide levels nor islet cell antibody and insulin antibody titer. A more rapid loss of stimulated C-peptide occurred in patients who lacked HLA-DR3 and -DR4 (P less than 0.05 at mo 9). CONCLUSIONS: This study shows a higher spontaneous clinical remission rate than expected during the 1st yr after diagnosis. Preserved beta-cell function at entry predicts a greater chance of entering a remission, and a more rapid loss of beta-cell function was seen in patients without HLA-DR3 and -DR4. PMID- 1737544 TI - Benefits and risks with glyburide and glipizide in elderly NIDDM patients. AB - OBJECTIVE: To compare the efficacy, benefits, and risks of glyburide and glipizide in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Twenty-one elderly outpatients (mean age 70 yr) were treated for 8 wk, after being dose-titrated to achieve a fasting plasma glucose (FPG) concentration of less than 7.8 mM with glyburide or glipizide in a randomized crossover trial. FPG and postprandial plasma glucose, serum C-peptide, and HbA1c levels were measured. In 13 patients, self-monitoring of blood glucose (SMBG) with a memory meter was performed seven times per week. RESULTS: Glipizide (11.9 mg) and glyburide (8.4 mg) produced similar fasting and postprandial plasma glucose and HbA1c concentrations. No significant differences in basal or stimulated C-peptide levels were detected. Despite a few patient reports of hypoglycemia, a high incidence of SMBG readings less than 4.5 mM was attributed to the use of both drugs. CONCLUSIONS: Both treatments proved effective for glycemic control; however, both second-generation sulfonylureas are associated with a significant risk of hypoglycemia in elderly NIDDM patients. The proper use of sulfonylureas in this population should include close surveillance of ambulatory glucose monitoring and intensive and repeated patient education about the risks of hypoglycemia. PMID- 1737545 TI - Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. AB - OBJECTIVE: We conducted an 8-wk controlled study with topical 0.075% capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy. Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal, chemical, and mechanical stimuli when applied topically. RESEARCH DESIGN AND METHODS: In 22 randomly assigned subjects, either capsaicin or vehicle cream was applied to painful areas 4 times/day. Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk. RESULTS: Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status, as measured by physician's global evaluation (P = 0.038) and by a categorical pain severity scale (P = 0.057). Decrease in mean pain intensity by a visual analogue scale was 16% in capsaicin-treated and 4.1% in vehicle-treated subjects. Mean pain relief on visual analogue scale was 44.6 and 23.2%, respectively. In a follow-up open-label study, approximately 50% of subjects reported improved pain control or were cured, and 25% each were unchanged or worse. A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time. CONCLUSIONS: Results from this preliminary study suggest that topical 0.075% capsaicin may be of value in subjects with diabetic neuropathy and intractable pain. PMID- 1737546 TI - Community-based epidemiological study on diabetes in Pu-Li, Taiwan. AB - OBJECTIVE: To determine the prevalence and possible risk factors associated with diabetes in Pu-Li, Taiwan. RESEARCH DESIGN AND METHODS: The project was a community-based cross-sectional study with stratified cluster sampling of residents greater than or equal to 30 yr of age. Medical students conducted home visit interviews with public health nurses, drew fasting blood samples from 1738 of 2573 registered residents greater than or equal to 30 yr of age in Pu-Li, Taiwan. RESULTS: The prevalence of diabetes, including those with a history of diabetes and newly diagnosed cases determined by modified World Health Organization criteria, was 12.4%. With the standard world population of Segi, the age-adjusted prevalences were 6.9% for previous diabetes and 4.4% for new diabetes. The age-specific prevalence of diabetes increased significantly with age for new diabetes cases but not for previously diagnosed cases. To study factors associated with diabetes, we first applied univariate analysis. Stratified analyses by age and sex were used for interaction assessment. A significant interaction effect on diabetes was found between age and sex. Logistic regression was used for multivariate analysis. The final model showed that, after controlling for all other covariates, the significant factors associated with diabetes were family history of diabetes (father and/or mother, yes vs. no, odds ratio [OR] 3.13, 95% confidence interval [CI] 1.17-8.33), obesity (yes vs. no, OR 2.69, 95% CI 1.09-6.63), and age (continuous, OR 1.04, 95% CI 1.00-1.08). Locality and physical activity were not significantly correlated with diabetes. CONCLUSIONS: The age-adjusted prevalence of diabetes in Pu-Li were 6.9% for previous diabetes and 4.4% for new diabetes. Possible risk factors associated with diabetes with logistic regression were family history of diabetes, obesity, and age. Locality and physical activity were not significantly correlated with diabetes. PMID- 1737547 TI - Relationship of self-efficacy and binging to adherence to diabetes regimen among adolescents. AB - OBJECTIVE: To test the hypothesis that poorer adherence to diabetes care is related to four variables associated with self-concept in adolescents with diabetes: self-esteem, self-efficacy, depression, and binging behavior. In addition, we expected adolescent females to be less adherent to diabetes care. RESEARCH DESIGN AND METHODS: We recruited 193 consecutive patients (aged 13-18 yr) with insulin-dependent diabetes mellitus during their regular quarterly visit to a diabetes clinic in a large urban hospital. Participants completed the Rosenberg Self-Esteem Scale, the Children's Depression Inventory, an assessment of the frequency of binging in the past 3 mo, and parallel forms of an adherence scale and a self-efficacy scale that were developed for use in this study. RESULTS: Adolescents who reported lower adherence tended to report lower self esteem (r = 0.45, P less than 0.001) and self-efficacy (r = 0.57, P less than 0.001), more depressive symptoms (r = -0.50, P less than 0.001), more binging (r = -0.36, P less than 0.001), and had higher HbA1c (r = -0.24, P less than 0.001) than those with higher adherence scores. Together, the psychological variables accounted for 50% of the variance in adherence. There was no sex difference in reported binging, but, as expected, adolescent females reported less adherence overall (F[7,184] = 2.5, P = 0.018). CONCLUSIONS: Treatment adherence in adolescents with insulin-dependent diabetes mellitus is associated with behavioral and psychological variables. These findings suggest that specific behavioral and cognitive interventions could be used to improve adherence in those individuals who lack confidence in their ability to perform diabetes related tasks. PMID- 1737548 TI - Increasing trend of outpatient management of children with newly diagnosed IDDM. Colorado IDDM Registry, 1978-1988. AB - OBJECTIVE: To examine the management of newly diagnosed insulin-dependent diabetes mellitus (IDDM) in Colorado over time and to determine the prevalence of outpatient care at IDDM diagnosis on a statewide basis. RESEARCH DESIGN AND METHODS: The Colorado IDDM Registry was used to assess medical care at the diagnosis of IDDM in 1182 patients less than 18 yr of age between 1978 and 1988. RESULTS: Twenty-three percent of children with IDDM in Colorado reported never being hospitalized during the diagnosis period. Treatment of IDDM at diagnosis (outpatient vs. inpatient) did not differ by age, sex, or ethnicity/race. Patients living in rural counties were less likely to have been treated as outpatients at diagnosis than those living in urban counties. Physicians at specialized diabetes clinics (e.g., The Barbara Davis Center for Childhood Diabetes and The Childrens Hospital) were more likely to treat newly diagnosed children in an outpatient setting than physicians not affiliated with these clinics. The proportion of patients receiving only outpatient care at IDDM diagnosis increased from 6% in 1978 to 35% in 1988. This increase can be attributed to three factors: 1) an increase in the number of Colorado children diagnosed at The Barbara Davis Center, where outpatient care is strongly advocated; 2) a change in treatment practices at The Childrens Hospital away from routine hospitalization at onset; and 3) a steady increase in outpatient care for newly diagnosed diabetic children by physicians who were not affiliated with the aforementioned specialized diabetes clinics. CONCLUSIONS: The relatively new practice of outpatient care at diagnosis of IDDM increased between 1978 and 1988 in Colorado, in both specialized diabetes clinics and physicians' practices not affiliated with specialized clinics. PMID- 1737549 TI - [Hypertension caused by endocrine disorders]. PMID- 1737550 TI - [Spontaneous hypoglycemia]. PMID- 1737551 TI - [The adrenal cortex and its hormones. A short description of theory and clinical aspects as well as introduction into some fundamental concepts in endocrinology]. PMID- 1737552 TI - [Hyperparathyroidism: pathology, diagnosis and therapy]. PMID- 1737553 TI - [Gynecological endocrinology]. PMID- 1737554 TI - [Adrenogenital syndrome]. PMID- 1737555 TI - [Literature services for nursing]. PMID- 1737556 TI - [Information gathering for nursing]. PMID- 1737557 TI - [Activities of daily living: nursing of a sickly nursing model]. PMID- 1737558 TI - [Cushing's disease and acromegaly. Treatment of hormone active pituitary adenomas]. PMID- 1737559 TI - [The quality of life after total gastrectomy for stomach carcinoma. Esophagojejunal plication with pouch versus esophagojejunostomy without pouch]. AB - A group of 178 patients with total gastrectomy for gastric carcinoma were divided into two groups matched for sex, age, tumour stage and follow-up interval (29 pairs, 46 men and 12 women; mean age 63.4 [39-74] years) according to the type of reconstruction performed, oesophagojejunal plication with pouch or simple oesophagojejunostomy without pouch. Those with left-extended gastrectomy, follow up period of 9 months or less, and local recurrence or metastasis were excluded. Quality of life was evaluated by means of three standardized questionnaires sent to all the patients: (1) general physical complaints; (2) satisfaction with life; and (3) psychosocial burden. Patients with pouch reconstruction declared more favourable results in 90 of the 94 questions contained in the questionnaire (96%) than the patients without pouch. Patients in the former group also had significantly fewer general physical complaints (P less than or equal to 0.05) and were significantly more satisfied with life (P less than or equal to 0.05) than those without pouch. Correlation analysis for the entire group (n = 58) indicated significant relationships especially between quality of life and postoperative nutrition and body weight. Technical surgical problems of total gastrectomy having largely been solved, the question of quality of life must increasingly determine the choice of treatment. PMID- 1737560 TI - [Complications in the course of the Muckle-Wells syndrome]. AB - A 35-year-old woman had since early childhood suffered from recurrent urticaria like rash, intermittent fever, arthralgia and pancochlear inner-ear deafness. At the age of 17 years she also developed a steroid-resistant nephrotic syndrome, found to be due to renal amyloidosis (type AA). The triad of renal amyloidosis, inner-ear deafness and recurrent urticaria is characteristic of Muckle-Wells syndrome, which has a hereditary basis. Rapidly progressive renal failure necessitated long-term haemodialysis and two renal transplantations. The accompanying immunosuppressive treatment with corticosteroids, azathioprin and, later, cyclophosphamide brought about a remission of the joint and skin abnormalities. After removal of the first donor kidney and termination of immunosuppressive treatment the syndrome recurred with subacute growth of an amyloid goitre as well as amyloidosis of the optic nerve. A few weeks before death a malignant non-Hodgkin lymphoma of the stomach was demonstrated. It was presumably a complication of long-term immunosuppression and not of the Muckle Wells syndrome. The patient died of the complications of combination chemotherapy. Necropsy revealed generalized amyloidosis. PMID- 1737561 TI - [The therapy of malignant melanoma]. PMID- 1737562 TI - [Amylin--a newly identified pancreatic peptide and its relationship to diabetes mellitus]. PMID- 1737563 TI - [Stents: intravascular, endoluminal and transparenchymatous]. PMID- 1737564 TI - [The therapy of arm venous thrombosis]. PMID- 1737565 TI - [Drains in the hospital]. PMID- 1737566 TI - [Percutaneous endoscopic gastrostomy]. PMID- 1737567 TI - [The prevention of nonsteroidal antirheumatic agent-associated gastropathy]. PMID- 1737568 TI - Ethical principles and guidelines for scientific experiments on animals. Swiss Academy of Medical Sciences and Swiss Academy of Sciences. PMID- 1737569 TI - Photon emission from normal and tumor human tissues. AB - Photon emission in the visible and near ultraviolet range by samples of human tissue removed during surgery has been measured by means of a low noise photomultiplier coupled to a data acquisition system. The results show that among the 25 analyzed samples the 9 from normal tissues had an emission rate of the order of some tens of photons/cm2 min, while most of the 16 tumor tissue samples had a very much higher rate. PMID- 1737570 TI - New C26 delta-lactones from the Dufour's gland of the urticating ant Tetramorium aculeatum. AB - (6R*)-[(2S*)-2-hydroxyheneicos-12-enyl]-5,6-dihydro-2H-pyran-2-one (1) degree is the major constituent of the secretion of freshly dissected Dufour's gland of the urticating ant Tetramorium aculeatum. In solution, compound 1 is slowly transformed into (1S*,5R*,7S*)-7-(nonadec-10-enyl)-2,6-dioxabicyclo[3.3.1] nonan 3-one (2) degrees on standing. The structures of compounds 1 and 2 have been established on the basis of their spectral and chemical properties. Compound 1 could be responsible for the urticating properties of the ant. PMID- 1737571 TI - Shock induces a long-lasting elevation of blood glucose in Aplysia. AB - Glucose, and not trehalose, was found to be the main blood sugar in Aplysia californica. Changes in blood glucose in response to stress produced by electric shock were measured in blood obtained both from animals dissected within ten minutes of shocking and from catheterized animals at various intervals, up to two and a half hours after the shock. Electric shock increased blood glucose levels. The rise in blood sugar continued as long as two and a half hours after shock. PMID- 1737572 TI - A study of macromolecular diffusion through native porcine mucus. AB - A diffusion chamber technique based on time-lag analysis for the estimation of effective diffusion coefficients of radiolabelled macromolecules of varying molecular weights through native mucus gel is reported. For all solutes studied, a reduction in effective diffusion coefficients was observed with a retardation of solute flux in both aqueous and mucus layers. Over the molecular weight range of solutes investigated (126-186,000 Daltons), a consistent effect of molecular weight was evident with regard to the retarding effect of mucus. No apparent or absolute molecular weight cut-off for macromolecular transfer was exhibited. However, at high molecular weights (greater than 30,000 Daltons) the retardation was greatly enhanced. The results confirm that mucus can be regarded as a gel with finite pores, but that it does not constitute an absolute barrier to even high molecular weight solutes. PMID- 1737573 TI - The endothelium-dependent relaxation of human middle cerebral artery: effects of activated neutrophils. AB - Neutrophils, activated by 4 beta-phorbol-12 beta-myristate-13 alpha-acetate, decreased acetylcholine-induced relaxation of strips of human middle cerebral artery precontracted with noradrenaline. This effect was prevented by catalase, but not by superoxide dismutase. Nifedipine, propranolol and, less markedly, captopril reduced the decrease in acetylcholine-induced relaxation. Aspirin and dipyridamole did not reduce it. PMID- 1737574 TI - Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation. AB - We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T' parallel order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T' parallel for a 3-h period at 37 degrees C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation. PMID- 1737575 TI - Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity. AB - The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae of Drosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm, Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M. PMID- 1737576 TI - Peptide YY enhances NaCl and water absorption in the rat colon in vivo. AB - Peptide YY (PYY) is thought to possess paracrine and endocrine functions. The highest concentrations of this peptide are in the colonic mucosa. The effect of PYY on electrolyte and water transport in the rat colon was studied in vivo. Under urethane anesthesia, rat colonic loops were perfused at a constant rate with physiological buffer solution containing phenol red as a nonabsorbable volume marker, and net movements of water, sodium, chloride and potassium in the perfused colon were determined every 10 min. Intravenous administration of PYY produced a dose-dependent increase in the net absorption of sodium chloride and water, as well as a decrease in the net secretion of potassium. PYY inhibited the reduction in net absorption of sodium chloride and water evoked by vasoactive intestinal peptide (VIP), but did not affect the VIP-evoked increase in net potassium secretion. These findings suggest that PYY acts as an enhancer of sodium chloride and water absorption and as an antagonist to VIP-induced secretion in the colon. PMID- 1737577 TI - Effects of ovariectomy on removal of collagen bundles in the postpartum uterus of the mouse. PMID- 1737578 TI - Proopiomelanocortin expression in the skin during induced hair growth in mice. AB - We demonstrate for the first time a hair cycle-dependent gene and protein expression of proopiomelanocortin in mouse skin in vivo. Northern blot detected POMC mRNA with an apparent size of 0.9 kb in anagen but not telogen skin. Western blot emphasized a specific protein of 30-33 kDa recognized by anti beta-endorphin in late but not early anagen or telogen skin. By immunocytochemistry, beta endorphin antigen was localized in the sebaceous gland in a hair cycle dependent manner. PMID- 1737579 TI - Multiplication of human-derived Pneumocystis carinii in severe combined immunodeficient (SCID) mice. AB - Clinically healthy SCID mice were infected intratracheally with Pneumocystis carinii (PC) of human origin. The data obtained provides unambiguous evidence that progressive multiplication of PC organisms of human origin takes place in the lungs of experimentally infected animals. SCID mice that were infected with human-derived PC also revealed a markedly greater number of mouse PC organisms in their lungs than the controls. All the SCID recipients of human PC died by day 65 post infection, whereas the controls, housed under identical conditions, started dying significantly later due to severe mouse pneumocystosis. This animal model could be used for the maintenance and propagation of human PC, and for evaluating strategies for treating human pneumocystosis. PMID- 1737580 TI - Transfer of T-cell mediated immunity to Hymenolepis nana from mother mice to their neonates. AB - Administration of lymph node cells from Hymenolepis nana-infected mice into lactating mothers, or directly suckling neonates successfully transferred immunity to the neonates. The capacity of lymph node cells to transfer immunity was completely abrogated by pretreatment with anti-Thy-1.2 monoclonal antibody and complement. PMID- 1737581 TI - Shape change of human blood platelets: reliable and fast detection by quasi elastic light scattering. AB - Quasi-elastic light scattering has been used for the first time to obtain reliable information about the morphology of platelets under physiological conditions within a short time. By measuring two independent parameters (electrophoretic mobility and diffusion coefficient) it is possible to distinguish between different stages of shape change on the one hand, and between shape change and binding of particles to the platelet surface without shape change on the other hand. PMID- 1737582 TI - Common antigenic properties of a g-type (goose) and a c-type (duck) egg white lysozyme: antibody responses in rabbits and mice. AB - Embden goose (GEWL) and Barbary duck (DEWL) egg white lysozymes possess different amino acid sequences corresponding to the g-type and c-type, respectively. GEWL was shown to be a better immunogen than DEWL in both rabbits and mice. The antigenicity of the two lysozymes was tested using different techniques (i.e. indirect ELISA, inhibition tests and immunoabsorption experiments). Injection of either GEWL or DEWL into rabbits and mice induced both specific antibodies and cross-reacting antibodies. Moreover, anti-GEWL antibodies, in contrast to anti DEWL antibodies, did not cross-react with hen egg white lysozyme (HEWL), a c-type lysozyme. While the structure of GEWL was not modified after binding to plastic, DEWL was denaturated, but it did keep some native epitopes. It was concluded that g-type and c-type lysozymes, which have different amino acid sequences, exhibit strong common antigenic properties. PMID- 1737583 TI - Variation in regulation of aflatoxin biosynthesis among isolates of Aspergillus flavus. AB - Two new phenotypes of Aspergillus flavus which exhibit novel patterns of aflatoxin production have been identified and characterized. In one of the new variants of A. flavus, aflatoxin is made in the absence of carbohydrate and concomitantly with growth, without a lag period. A second variant did not produce aflatoxin in the presence or absence of carbohydrate. Chemical mutagenesis of this nonaflatoxigenic strain resulted in mutant strains which produced aflatoxin on carbohydrate-containing media. The aflatoxin production pattern observed in these mutants resembled the typical production scheme, with a lag period through log phase growth. PMID- 1737584 TI - A new cell line (XTY) from a tumor of Xenopus laevis. AB - A new cell line (XTY) was derived from a tumor of a female Xenopus laevis. This cell line has been proliferating in standard amphibian culture medium for more than 4 years (470 generations) and has a doubling time of 75.5 h at 25 degrees C. The cells aggregate into large groups, and their stellate morphology and the expression of desmin demonstrated by immunocytochemistry suggest that their origin is not epithelial. PMID- 1737585 TI - Chemical basis of pupal cannibalism in a caterpillar (Utetheisa ornatrix). AB - The moth Utetheisa ornatrix derives protection against predation from systemic pyrrolizidine alkaloids (PAs) that it sequesters as a larva from its foodplants (Leguminosae, Crotalaria spp.). We here show, in laboratory tests, that Utetheisa deficient in body PA can make up for the chemical shortfall by cannibalizing pupae. We present evidence indicating that cannibalism in larvae is elicited not by hunger, but possibly by PA deficiency itself, and that in making cannibalistic choices larvae prefer PA-containing over PA-free pupae. PAs themselves, either in crystalline form or as additives to food items, proved phagostimulatory to larvae. In nature Utetheisa tend to pupate away from their foodplant, essentially out of reach of larval attack. The threat of cannibalism may have contributed to the evolution of this pupation behavior. PMID- 1737586 TI - 24th annual meeting of the Swiss Societies for Experimental Biology (USGED/USSBE). March 19-20, 1992, Basel. Abstracts. PMID- 1737587 TI - Rapid cytological diagnosis during thyroid surgery. AB - The authors report the results of the use of intra-operative cytological examinations of the thyroid gland. In their hands, the method has a 96.3% accuracy in 757 patients with thyroid disorder. Benign conditions and malignant tumours can be correctly diagnosed. False negative diagnosis can arise with well differentiated follicular carcinoma and the differentiation of follicular adenoma may be difficult. Atypical adenomas may give a false positive diagnosis. The incorrect diagnosis of chronic lymphocytic thyroiditis is unlikely when sufficient attention is given to the whole clinical picture. PMID- 1737588 TI - Breast cancer: a study into the value of a historical group as comparative material for new methods of treatment. AB - A large group of consecutive patients were studied who had been treated for a primary breast carcinoma by a radical mastectomy at the Netherlands Cancer Institute, during the period of 1960-1974. One of the objectives of that retrospective study was to record the results of treatment of a historical group of patients in such a way that they could presumably serve as a reference for new methods of treatment of breast cancer. To verify the validity of this presumption, the present study compares the treatment results of patients from the EORTC trial 10801, which addresses the value of breast conserving procedures, with that of matched controls from the historical group mentioned above. Matching was carried out with respect to the following prognostic factors: age, tumor size, localization, (number of) positive axillary nodes and grade of malignancy. Analysis of the results strongly suggests that the prognosis for the patients from the historical group is worse than for both groups of patients from the trial 10801. Therefore, this study again confirms that a historical group is not suitable as comparative material for new ways of treatment of breast cancer, and that prospective randomized studies are required to test new treatment schedules. PMID- 1737589 TI - Multicentric breast tumour: an anatomical-clinical study of 100 cases. AB - Multicentric tumours (MT) represent a potential limit to the treatment by conservative surgery of cancer of the breast. In order to determine which anatomical-clinical features of breast cancer would indicate the highest risk of MT, we studied 100 patients with MT and 452 patients with unicentric tumours (UT), all of whom had been subjected to radical mastectomy during the period 1980 to 1988. Statistical analysis showed a significant difference between the two groups of parameters for bilateral breast cancer (with regard both to metachronous and synchronous lesions), for primary tumours of over 2 cm in size, for both lobular and invasive ductal histotypes and for involvement of the nipple areola complex. Therefore, if the indications in favour of conservative surgery are applied accurately in combination with radiation therapy, the clinical and biological significance of multicentricity is minimized. PMID- 1737590 TI - Prognostic value of serum levels of immunoglobulins (IgA, IgM, IgG, IgE) in patients with colorectal cancer. AB - In the present study, the serum immunoglobulin levels of 100 patients with colorectal cancer who had undergone antitumor therapy, were measured before and during therapy. We received three samples before therapy and further samples every 2 months after initiation of therapy. It was found that the group of patients having increased IgG (P less than 0.05) and perhaps IgM (P less than 0.1) levels showed a longer time to progression of disease and prolonged overall survival time. Based on this finding we conclude that survival can potentially be correlated with immunoglobulin levels. Studies with large numbers of patients, and orientated towards the correlation of immunoglobulin levels with specific clinical parameters may prove that immunoglobulins can play a prognostic role in survival for colorectal cancer patients. PMID- 1737591 TI - The prognostic value of argyrophil nucleolar organiser regions (AgNORs) in colorectal cancer. AB - Argyrophil nucleolar organiser regions (AgNORs) are increased in a variety of malignant cells compared with normal cells, and a recent study has claimed that AgNORs have prognostic value in colorectal cancer. We have studied the AgNOR counts in tumours from 95 colonic resections performed in 94 patients in whom a minimum 5 year follow-up was available. In 71 pathological specimens adjacent normal mucosa was also examined. There was a significant difference between AgNORs per cell in normal mucosa (median 1.46, range 1.10-1.80) compared with tumour cells (median 1.92, range 1.42-2.95, P less than 0.001). There were no significant differences in average AgNORs per cell between tumours in each Dukes' stage or category of differentiation. The average AgNORs per cell in tumours of patients surviving disease-free for 5 years was the same as that in tumours of patients dying of colonic cancer recurrence. We conclude that AgNORs have no prognostic value in colorectal cancer and are not correlated with Dukes' staging or differentiation of the tumour. PMID- 1737592 TI - Combination of serum carcino-embryonic antigen and C-reactive protein--a useful test in preoperative staging of colorectal cancer. AB - The value of the simultaneous estimation of serum carcino-embryonic antigen (CEA) and C-reactive protein (CRP) concentrations in staging patients with colorectal neoplasias was evaluated. The study included 95 patients with benign or malignant epithelial tumors of colon and rectum. The simultaneous negative values of CEA and CRP were able to exclude stage D tumors with a specificity of 92.6% (P less than 0.001). Simultaneously positive values of CEA and CRP were able to diagnose stage C or D tumors with a specificity of 92.1% (P less than 0.001). It is concluded that the combination of CEA and CRP tests can substantially contribute to the preoperative staging and assessment of the extent of colorectal cancer. PMID- 1737593 TI - Assessment of breast cancer size: a comparison of methods. AB - Two hundred women presenting with primary breast carcinoma were studied to find the most accurate single or combination of methods to assess breast tumour size. Correlations of the maximum clinical, mammographic and ultrasound tumour diameter were made with maximum histological diameter. Tumour size could be assessed clinically in all 200 patients, and overestimated the size of small tumours and underestimated large tumours (P less than 0.001). Mammographic measurement, which was possible in 145 (72.5%), underestimated the size of large tumours (P less than 0.01). Only 100 women underwent ultrasound examination (size assessed in 86%) and this modality tended to underestimate the size of all tumours (P less than 0.05). All methods of measurement showed similar correlations with histological size. Stepwise linear regression showed that the most accurate and practical estimation could be made using the formula: Histological size = 0.5 x mammographic size + 0.5 x clinical size. We conclude that clinical measurement of breast cancer size is as accurate as that from mammography or ultrasound. Accuracy can be improved by the use of a simple formula of both clinical and mammographic measurements. PMID- 1737594 TI - Breast reconstruction using latissimus dorsi island flap without an endoprosthesis. AB - Breast reconstruction using a modified latissimus dorsi island flap is presented. The whole muscle is raised on its vascular pedicle, folded beneath the skin island and sutured in layers, thus substituting the volume of an endoprosthesis. The method may give satisfactory results in carefully selected cases (mostly in women with a small contralateral breast). It can also be applied in reconstruction after subcutaneous mastectomy. PMID- 1737595 TI - Radioimmunoscintigraphy of metastatic breast carcinoma. AB - Seventeen patients with breast cancer underwent preoperative radioimmunoscintigraphy (RIS). Planar and tomographic imaging techniques (single photon emission computerised tomography--SPECT) were studied using Indium-111 labelled anti-epithelial membrane antigen (EMA) antibodies for tumour localisation. Overall imaging sensitivities were reasonable with correct identification of around 90% of primary lesions and 50% of secondary lesions. Planar imaging was more sensitive than SPECT for identification of superficial lesions such as the primary lesions (88% vs 56%) and axillary metastases (59% vs 53%). SPECT was necessary, however, for detection of deeper lesions such as internal mammary chain metastases and often served as an adjunct rather than an alternative to planar imaging. RIS, therefore, may contribute to more accurate staging of breast cancer, although further technical advances in RIS would enhance this contribution. PMID- 1737596 TI - MRI or CT in the preoperative diagnosis of bone tumours. AB - The value of magnetic resonance imaging (MRI) and computed tomography (CT) in the diagnosis of bone tumours was investigated in a prospective study of 25 patients. MRI is superior to CT because it permits multidirectional exposures. Moreover, the tumour can be readily distinguished from the neurovascular structures without injection of contrast medium. MRI gives better contrast than CT, making it possible to study the relationship to the soft tissues, bone marrow and joints more accurately. On the other hand, CT gives a better picture of the destruction of cortical bone. With neither MRI nor CT can the exact tumour length be measured. Neither MRI nor CT permits an exact, reliable diagnosis. Owing to the relatively slow exposure technique in combination with respiratory movements, depiction of the thoracic wall is less satisfactory with MRI than with CT. If both techniques are available, MRI is preferred. In view of the fact that MRI apparatus is still less widely available, it should be borne in mind that CT also allows an adequate investigation of skeletal lesions. PMID- 1737597 TI - Acinic cell carcinoma of the salivary glands. A long term follow-up study of 15 cases. AB - Fifteen cases of acinic cell carcinoma of the salivary glands were evaluated retrospectively with respect to histological and clinical data. DNA content assessment was carried out in six cases by cytophotometry. The majority of tumors were located in the parotid gland and were Stage I at presentation. There was a female predominance and the mean age at primary diagnosis was 51.2 years for females and 41.0 for males. The solid-acinar cell pattern was the most frequently observed and the tumors were 'diploid' in all the six cases studied. Surgery was the therapeutic modality in all cases (enucleation in seven, superficial parotidectomy in three and total parotidectomy in five) and, in four of them, was complemented with radiotherapy. The clinical course was characterized by recurrence in 10 cases, metastases occurred in three patients and one patient died of the tumor. Of the seven recurrent cases, six were treated by enucleation and one by superficial parotidectomy. The histological pattern showed no correlation with the clinical course or DNA content. Acinic cell carcinoma has a significant morbidity with a high recurrence rate which seems to be largely influenced by the type of surgery employed. Wide surgical excision of the neoplasia, which includes total parotidectomy in the parotid cases, is recommended in order to reduce the frequency of recurrence of the tumor. PMID- 1737598 TI - Primary breast carcinoma in patients with malignant melanoma. AB - Malignant melanoma and primary breast cancer are tumours which have an association based on genetic and hormonal factors. It is not generally appreciated that there is an increased incidence of melanoma in patients with breast cancer and vice versa. We present two cases of patients who developed breast carcinoma following previous treatment for melanoma. We review previous reports of this association and examine the theoretical reasons why this should be so. Medical practitioners should be aware of this association in order to alter their index of suspicion appropriately. PMID- 1737599 TI - Malignant schwannoma of the breast. AB - A case of rare, malignant schwannoma of the breast has been analysed with regard to its history and diagnostic problems, such as the mammographic pattern and the role of cytology in the preoperative mesenchymal suggestion. PMID- 1737600 TI - Sinus lift grafts and endosseous implants. Treatment of the atrophic posterior maxilla. AB - Patients from multicenters were treated with sinus lift graft operations and placement of implants. Surgical procedures healed uneventfully with minimum pain, swelling, or morbidity. Grafts healed with few complications or failures. Implants placed into the grafts support prosthetic reconstruction and are predictable over time. The question of what graft material to use is discussed. Grafts of non-resorbable HA (Interpore 200), bovine cortical HA (Bio-Oss), resorbable HA (OsteoGen), and freeze-dried demineralized bone powder and granules are presented. Results of biopsy, histometry, backscattered electron microscopy, cell labeling, and special stain suggest consistent bone growth into a variety of graft materials. In the authors' opinion investigation must continue to 1. Determine the healing time for different graft materials. At present, anecdotal evidence suggests that sinus grafts of autogenous bone heal for 4 to 6 months; freeze-dried demineralized bone heals for 12 to 16 months; and alloplastic materials with freeze-dried demineralized bone heal for 9 to 11 months. 2. Evaluate histologic evidence of bone growth into different bone replacement graft materials. 3. Evaluate the long-term follow-up and success of implants placed within sinus grafts. 4. Determine the remodeling potential of different hard tissue graft materials under implant functional loads. PMID- 1737601 TI - The Integral Implant System: prosthetic considerations. AB - Patients who are totally edentulous and who have been doomed to discomfort, pain, and dysfunction because of the inability to use complete dentures have been rehabilitated using various implant systems. Implants should only be considered after exhaustive medical history taking and diagnostic wax-ups. A variety of prosthetic techniques can be employed to restore various forms of edentulism. The Integral Implant System has proven to be a highly successful foundation to restore the patient to optimum function. PMID- 1737602 TI - The history of the diagnosis and treatment of ectopic pregnancy: a medical adventure. AB - From its indirect reference by Abulcasis (936-1013) and until the 19th century the ectopic pregnancy was known as a universally fatal accident. By reporting successful treatment of tubal pregnancy with salpingectomy in 1884 Robert Lawson Tait (1845-1899) started an era of almost 70 years of exclusively extirpative treatment of ectopic pregnancy. The technologic revolution of the 20th century improved diagnostic capabilities so that diagnosis of unruptured ectopic pregnancy becomes feasible and even mandatory. Side by side our understanding of the natural history of ectopic pregnancy improved. Many patients with early resolving ectopic pregnancies escape surgical treatment. Preservation of future fertility became possible with the introduction of conservative surgical procedures and with the use of methotrexate. The main achievement in the treatment of ectopic pregnancy over the past 110 years is the dramatic decrease in mortality rate: from 72-90% in 1880 to 0.14% in 1990. PMID- 1737603 TI - Detection of Candida cell forms in Pap smears during pregnancy. AB - In a prospective study of 124 urban black pregnant women, 43% had Candida isolated from endocervical cultures and 20% had Candida cell forms on cytological Pap-stained cervical specimens. The presence of Candida cell forms on Pap smears had a better correlation with Candida colonisation when normal lactobacillary flora was present, when Trichomonas vaginalis parasites were absent and when the infecting Candida species was C. albicans. Positive cultures were strongly related to a number of clinical signs and symptoms, but Pap smears were not. Neither Candida culture nor Candida cells in Pap smear revealed an association with premature delivery, birth weight, severe neonatal morbidity or mortality. We confirm that the routine cervical Pap smear is not a sensitive method for diagnosing symptomatic fungal infection. More specifically, some of the Pap smear characteristics, such as disturbed lactobacillary flora or co-infection with T. vaginalis, interfere with accurate diagnosis. PMID- 1737604 TI - Folate status during pregnancy: relationship with alcohol consumption, other maternal risk factors and pregnancy outcome. AB - This study was designed to identify the factors affecting folate status in pregnant women and to explore the relationship between folate status and alcohol consumption during pregnancy. For this purpose, 347 French women were recruited during 1985-1986 on their first visit to the antenatal clinic at Roubaix Hospital (northern France). Alcohol consumption was ascertained by a standardized interview. Folate status assessment was available for 246 pregnant women who were not given folate supplementation. Average folate levels during pregnancy were lower among young women and smokers. Serum folate values diminished with the educational level, and red cell folate values increased with high parity. Unexpectedly, high red cell folate values were strongly related with high alcohol consumption after adjustment for the maternal risk factors associated with alcohol consumption and folate status. This was probably because in the Roubaix region where the study was conducted women consume mostly beer, which contains folates. Pregnancy outcome was not related to folate levels; birthweight was negatively associated with alcohol consumption during the first trimester of pregnancy. PMID- 1737605 TI - Incidence and cause of postpartum urinary stress incontinence. AB - Urinary leakage was reported in 53.5% of our patients at least once during pregnancy. Multigravidae and women older than 30 were affected more often than primigravidae or women younger than 30. 6.2% of all women, who were continent before pregnancy, developed permanent stress incontinence after vaginal delivery. As a conclusion, it can be said, that vaginal delivery itself predisposes for permanent stress urinary incontinence (SUI). Factors, which increase the trauma to the pelvic floor (tear, no episiotomy, forceps or vacuum extraction), show a higher incidence of postpartum persisting SUI without statistic significance. Labour management with epidural anaesthesia showed a statistically proven lower incidence of postpartum persisting SUI in comparison to the pudendal block. PMID- 1737606 TI - Successful treatment of failed AID cases by use of gamete intra-fallopian transfer using donor semen (GIFT (D)). AB - Over a 13-month period in a newly opened assisted conception unit at the Women's Hospital, Liverpool, gamete intra-fallopian transfer using donor semen, GIFT (D) was offered to eighteen couples who had failed to conceive after numerous cycles of treatment with artificial insemination by donor semen (AID). The indication for the use of donor semen was either azo- or severe oligoaesthenospermia, and, in addition, the female partners have been exhaustively investigated with no major cause found to account for the couple's infertility. Using a basic clomiphene citrate and human menopausal gonadotrophin protocol it was possible to achieve a pregnancy rate of 56% per GIFT (D) cycle. As a consequence of these results it is now our policy to treat couples whose infertility is due to an unresolvable male factor with AID for 12 cycles only. If they have been unsuccessful in achieving a pregnancy after this time, they are offered GIFT (D). PMID- 1737607 TI - Oxygen tension in follicular fluid falls with follicle maturation. AB - The increase in follicular diameter during maturation is accompanied by an increase in vascular supply. The oxygen tension (PO2) in the follicular fluid of the growing follicle should therefore give an insight whether the oxygen delivery during this pertinent process is sufficient. Follicular fluid of 20 patients subjected to in vitro fertilization and embryo transfer were sampled in heparinized glass capillaries which were placed between the puncturing needle and the collecting reservoir. All patients were treated with human menopausal gonadotropin (HMG) and follicle-stimulating hormone (FSH). The PO2, PCO2 and pH of the follicular fluid were measured with an automatic gas analyser (Ciba Corning). Simultaneously, the same parameters were estimated in maternal capillary blood taken from the arterialized well perfused earlobe. Follicular size was measured by ultrasound. With growing follicular size (FS), the oxygen partial pressure (PO2) fell from 80 to 50-60 mmHg (PO2 = 114.4-3.3.FS; r = 0.79) while the carbondioxide partial pressure (PCO2) in the follicle increased from 35 to 50 mmHg (PCO2 = 15.1 +/- 1.9.FS; r = 0.71). In correlation to these results, the pH in follicular fluid fell from 7.40 to 7.30 (pH = 7.6-0.019.FS; r = 0.62). The correlation between the PCO2 and the pH demonstrates a deviation from the regression line if no metabolic alterations take place (delta log PCO2/delta pH = -0.69). The increase in ovarian blood flow during follicular maturation is obviously not sufficient to bridge the growing diffusion distance between the capillary network surrounding the follicle and its center.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737608 TI - Sister chromatid exchange frequencies in a group of individuals with unfavorable reproductive health. AB - Sister chromatid exchange (SCE) frequencies and other cytogenetic parameters were investigated in peripheral blood lymphocytes from 92 subjects comprising 44 parents of malformed offspring or repeated fetal wastage (Group I) and 48 controls, age and sex matched, having normal reproductive health (Group II). The karyotypes were normal and the mean mitotic indices were comparable in both groups. The mean frequency of SCE per metaphase in Group I (8.67 +/- 0.32) was significantly higher than the mean for group II (6.65 +/- 0.16), and the cellular replicative index in Group I (1.78 +/- 0.04) was significantly different from that of Group II (1.66 +/- 0.03). The results are discussed in the light of the present understanding of the etiology and mechanism of production of sister chromatid exchanges. PMID- 1737609 TI - Lifestyles of men in barren couples and their relationships to sperm quality. AB - This study is based on a questionnaire which focused on the possible association between lifestyle factors and male fertility in a group of 252 men attending our laboratory in connection with a fertility investigation. Their answers were correlated to sperm quality. No association could be documented between sperm quality and smoking habits, coffee drinking, a moderate alcohol intake, exposure to heat (sauna, hot baths, type of underwear, sedentary activities) or physical activities in their leisure time. In contrast, the reported average ejaculation frequency was significantly positively correlated to the motility of the sperm (% progressive) but inversely related to the proportion of sperm with abnormal morphology and semen volume. This indicates that the lifestyle of the subject has little, if any, impact on semen quality, at least within the limits recorded in the present study. PMID- 1737610 TI - Hormone replacement therapy and changes on pituitary function. AB - The aim of this study is to know how the pituitary function is affected by several delivery systems of estrogen replacement therapy. 116 menopausal women (54 natural and 62 surgical) were placed into three groups that received replacement therapy and in one control group. We determined prolactine (PRL), gonadotropins and 17 beta-estradiol (E2). We found a decrease in gonadotropin levels in treated patients with a natural menopause, and an increase in gonadotropin levels in the groups treated with conjugated estrogens in surgical menopausal women. 17 beta-E2 was found to be increased in all treated groups, mainly in the continuous therapy group (P less than 0.05). PRL was found to be decreased in patients treated with conjugated estrogens (oophorectomized and not oophorectomized) (P less than 0.05). Although these differences can not be attributed to the presence of the ovaries, we think that they may be the result of the treatment. PMID- 1737611 TI - Intranasal administration of estradiol in combination with progesterone to oophorectomized women: a pilot study. AB - A pilot study was done to investigate the pharmacokinetics and acceptability of an intranasal 17 beta-estradiol/progesterone formulation. This formulation contained dimethyl-beta-cyclodextrin as a solubilizer and absorption enhancer of the steroid hormones. The study was performed in four oophorectomized and hysterectomized patients. After nasal delivery of 0.34 mg estradiol and 0.85 mg progesterone, concentration-time curves of progesterone, estradiol and its metabolite estrone were established. Rapid absorption of progesterone and estradiol was demonstrated. Progesterone peak-levels (3.9-6.7 nmol/l) exceeded the levels which are found in the follicular phase of the menstrual cycle, but did not reach the levels of the luteal phase. Comparison with an earlier reported study in which only estradiol was administered shows that the addition of progesterone does not alter the absorption and pharmacokinetics of estradiol. The nasal formulation was well accepted by the four patients and no adverse effects were noted. PMID- 1737612 TI - Disturbed reproductive performance in extreme folic acid deficient golden hamsters. AB - We studied the effects of folic acid-deficient diets on maternal red blood cell folate level and reproductive performance in golden hamsters (Mesocricetus auratus, Waterhouse). Animals on the same day of oestrous cycle were put together and finally divided into three groups. Each group comprised at least 12 mature female hamsters. The animals were given three different diets, which were commenced before mating. The feeding regimens comprised a standard diet (group 1), or a folic acid-deficient diet which started either 2 weeks (group 2) or 16 weeks (group 3) prior to mating. The regimens were continued until sacrifice of the animals on day 9 of pregnancy. Pregnancy was realized by caging a male with a selected female during the night of ovulation. Just prior to sacrifice, blood samples were drawn to measure maternal folic acid levels in red blood cells. The pregnant uteri were removed and the embryonic sacs were carefully dissected away from the uterus. The number of sacs per pregnant animal was noted. Extreme folic acid deficiencies were confirmed in the pregnant golden hamsters on a folic acid deficient diet which started 16 weeks prior to mating as compared to those on a standard diet and on a folic acid-deficient diet which started 2 weeks prior to mating. This deficiency appears to interfere with normal reproductive performance. It caused early embryonic loss several days after mating and resulted, finally, in restoration of the oestrous cycle. PMID- 1737613 TI - Prognosis for pre-eclampsia complicated by 5 g or more of proteinuria in 24 hours. AB - Forty-two women with pregnancies complicated by pre-eclampsia and heavy proteinuria greater than or equal to 5 g/24 h were referred for conservative management to the high-risk obstetric unit in the John Radcliffe Hospital, Oxford, over a period of 5 years. Hyperuricaemia preceded the onset of heavy proteinuria in all 42 women. Most of the women had severe hypertension, but none developed eclampsia and there were no major maternal complications. Delivery was necessary within 2 weeks of onset of severe proteinuria in 88.1% of cases, although in some very preterm pregnancies delivery could be deferred for 3 or more weeks. Thirty-five women (83%) were delivered by caesarean section, 91% of whom were delivered urgently before the onset of labour. The high rate of urgent preterm operative delivery underlines the uncertainty of advanced pre-eclampsia and the need for close monitoring if delivery is to be deferred. Perinatal mortality was high; all the perinatal deaths occurred in babies of less than 29 weeks gestation. Despite heavy proteinuria, postpartum recovery was good. Three months after delivery, all but one patient had no significant proteinuria. There was no evidence of residual renal dysfunction. Although the outlook for pre eclampsia with heavy proteinuria is limited, in a few cases pregnancy can be prolonged for significant periods of time without apparently prejudicing maternal safety and permitting enhancement of maturity at birth. The observations justify cautious conservative management even when heavy proteinuria is present. PMID- 1737614 TI - Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers. AB - Max is a heterodimeric partner of the Myc oncoprotein with sequence-specific DNA binding activity. We found that the DNA-binding activity of bacterially expressed Max homodimers was inhibited in an ATP-dependent reaction by phosphorylation in vitro with purified bovine casein kinase II (CKII). In contrast, phosphorylation of Max and/or Myc by CKII had no inhibitory or stimulatory effect on the DNA binding activity of Myc/Max heterodimers. By deletion analysis and site-directed mutagenesis, the inhibitory domain was localized to a CKII phosphorylation site in the amino terminus of Max. Finally, extracts prepared from NIH-3T3 cell lines that overexpress Max contained a phosphorylated Max protein which, following phosphatase treatment or heterodimerization with Myc, was capable of sequence specific DNA-binding activity. Immunoprecipitation experiments confirmed that Max was also phosphorylated in NIH-3T3 cells, demonstrating that Max phosphorylation may have an important physiological function. PMID- 1737615 TI - Active genes in budding yeast display enhanced in vivo accessibility to foreign DNA methylases: a novel in vivo probe for chromatin structure of yeast. AB - Unlike higher eukaryotes, where an inverse correlation has been generally observed between gene expression and methylation of CpG sites, the budding yeast Saccharomyces cerevisiae lacks DNA methylation. Gene regulatory mechanisms can function independently of DNA methylation in yeast, and yeast strains expressing foreign DNA methylases that modify adenine and CpG residues have been found to be viable. We have used such strains to determine whether the transcriptional status of genes can influence the level of their DNA methylation in vivo. Several genes were tested, for example, GAL1, -7, and -10, PHO5, HMRa and HML alpha, and STE2 and STE3. Surprisingly, we found that all the genes displayed severalfold more methylation in the expressed state as compared to the repressed state. This procedure serves as a novel in vivo probe for the chromatin structure of yeast and potentially for higher eukaryotes. PMID- 1737616 TI - Saccharomyces telomeres assume a non-nucleosomal chromatin structure. AB - The chromatin structures of the telomeric and subtelomeric regions on chromosomal DNA molecules in Saccharomyces cerevisiae were analyzed using micrococcal nuclease and DNAse I. The subtelomeric repeats X and Y' were assembled in nucleosomes. However, the terminal tracts of C1-3A repeats were protein protected in a particle larger than a nucleosome herein called a telosome. The proximal boundary of the telosome was a DNase I hypersensitive site. This boundary between the telosome and adjacent nucleosomes was completely accessible to Escherichia coli dam methylase when this enzyme was expressed in yeast, whereas a site 250 bp internal to the telomeric repeats was relatively inaccessible. Telosomes could be cleaved from chromosome ends with nuclease and solubilized as protein-DNA complexes. Immunoprecipitation of chromosomal telosomes with antiserum to the RAP1 protein indicated that RAP1 was one component of isolated telosomes. Thus, the termini of chromosomal DNA molecules in yeast are assembled in a non nucleosomal structure encompassing the entire terminal C1-3A tract. This structure is separated from adjacent nucleosomes by a region of DNA that is highly accessible to enzymes. PMID- 1737617 TI - Induction of specific macronuclear developmental mutations by microinjection of a cloned telomeric gene in Paramecium primaurelia. AB - In Paramecium, the differentiation of a highly polyploid macronucleus from a diploid nucleus is accompanied by an extensive reorganization of the genome, involving reduction in chromosome size and formation of new telomeres at heterogeneous, but reproducible, positions. The results presented here, as well as work by others, indicate that telomere addition regions are not strictly determined by the micronuclear sequence, but are at least partially controlled by the old macronucleus. It is shown that microinjecting a high copy number of a plasmid containing the G surface antigen gene into the macronucleus of wild-type cells specifically modifies the processing of the G gene-bearing micronuclear chromosome at the following autogamy. Telomeric repeats are added upstream of the gene, rather than at their wild-type position 5 kb downstream of its 3' end, resulting in the deletion of the gene from the new macronucleus. This macronuclear mutation is unstable at the following autogamy, giving rise to many different telomere addition regions in different postautogamous clones. However, after several successive autogamies, cell lines can be obtained in which the telomeres reproducibly form in the same region. In crosses with wild-type cells, these macronuclear mutations show cytoplasmic inheritance; the micronuclei of the mutants are shown to be fully functional. The implications for the mechanism of choice of telomere addition sites are discussed. PMID- 1737618 TI - A specific ovarian tumor protein isoform is required for efficient differentiation of germ cells in Drosophila oogenesis. AB - Mutations within the ovarian tumor (otu) gene result in abnormal ovarian development. It has been proposed that otu phenotypes result from abnormal germ cell division and differentiation. To understand better what role otu performs in oogenesis we have undertaken an analysis of protein expression from the otu locus. Anti-otu antibodies recognize two proteins from Drosophila ovary extracts with apparent molecular masses of 98 and 104 kD. Sequence analysis of otu cDNAs suggests that these proteins are translated from two mRNAs generated by alternative splicing of a 126-bp exon between the sixth and seventh exon of the smaller transcript. Analysis of otu protein expression in eight mutants indicates a correlation between the accumulation of the 104-kD isoform and predifferentiated germ cells and suggests that there is a developmental shift in the accumulation of the two isoforms upon differentiation of germ cells. Furthermore, the 104-kD isoform appears to be required for efficient differentiation of germ cells. Immunostaining of otu proteins is restricted to the cytoplasm of germ cells, and a rapid loss of oocyte immunostaining during stage 11 suggests that there is a rapid and selective degradation of otu proteins within the oocyte but not within its 15 interconnected nurse cells. PMID- 1737619 TI - DNA sequence requirements for generating paused polymerase at the start of hsp70. AB - RNA polymerase II is transcriptionally engaged but paused approximately 25 nucleotides from the start site of the hsp70 gene of Drosophila melanogaster in uninduced (non-heat-shocked) flies. Here, we identify regions of the hsp70 promoter that are required for formation of this paused polymerase. Various hsp70 promoter sequences are substituted for promoter sequences of a yolk protein gene, yp1, which, in males, is normally not expressed and has no paused polymerase. Run on assays with nuclei of male transgenic flies are used to measure the level of paused polymerase on the hybrid genes. Sequences that reside upstream of the hsp70 TATA element, when fused upstream of the yp1 TATA element, specify the formation of a paused polymerase on the 5' end of this hybrid gene. Within this region are multiple copies of the GAGA element, which is known to bind a constitutively expressed factor. This element appears to play a role in generating the pause. Also, in the absence of much of this upstream region, hsp70 sequences in the vicinity of the transcriptional start and pause site participate in specifying the pause. Deletions of the pause site reduce the level of paused polymerase but do not lead to constitutive transcription. However, a connection between transcription and pausing is seen. The level of paused polymerase on the various hybrid hsp70-yp1 promoters correlates with the promoter's potential to direct heat-induced transcription. PMID- 1737620 TI - TFIID can be rate limiting in vivo for TATA-containing, but not TATA-lacking, RNA polymerase II promoters. AB - We have studied the effect of exogenous expression of the basal transcription factor TFIID on the activities of several different TATA-containing and TATA lacking promoters. Overexpression of TFIID from a transfected plasmid in Drosophila Schneider cells resulted in substantial concentration-dependent increases in expression from a cotransfected minimal TATA-containing promoter. Overexpression of TFIID activated expression from all TATA-containing promoters tested, with the maximum level of activation being inversely proportional to the strength of the promoter. In contrast, expression from TATA-less promoters was not enhanced, and could in fact be reduced, by increased expression of TFIID. Consistent with these findings overexpression of TFIID had opposite effects on Sp1-mediated activation observed from minimal synthetic promoters consisting of Sp1-binding sites and either a TATA box or initiator element. We discuss the significance of these results in terms of the role of TFIID in the initiation of transcription and as a possible regulatory target for expression from TATA containing promoters, as well as the role TFIID may play in expression from TATA less promoters. PMID- 1737621 TI - Extinction of alpha 1-antitrypsin gene expression in somatic cell hybrids: evidence for multiple controls. AB - Expression of the liver-specific alpha 1-antitrypsin (alpha 1AT) gene is extinguished in hepatoma/fibroblast hybrids. To define the mechanism of extinction, we identified DNA sequences involved in this process by transiently transfecting mutant alpha 1AT promoters into parental and hybrid cells. The wild type alpha 1AT promoter (-554 to +44 bp) was highly expressed in rat hepatoma cells, but activity was 100-fold less in fibroblasts or cell hybrids. Mutations in this region failed to activate alpha 1AT expression in nonhepatic cells, but mutations in the binding site for liver factor B1 (LF-B1) reduced hepatic specific expression greater than 100-fold. Furthermore, the hybrid cells failed to express LF-B1-binding activity and mRNA. This suggested that alpha 1AT extinction in hybrids might be an indirect, lack-of-activation phenotype mediated primarily through repression of LF-B1. To test this possibility, we stably transfected an LF-B1 expression cassette into parental and hybrid cells and monitored expression of transfected and endogenous alpha 1AT genes. Surprisingly, although constitutive LF-B1 expression could activate alpha 1AT-CAT transgenes in these cells, it neither prevented nor reversed extinction of the chromosomal alpha 1AT genes. We conclude that although extinction of the LF-B1 trans activator accompanies alpha 1AT extinction in cell hybrids, it does not play a causal role in this process. PMID- 1737622 TI - Relevance of Ki-67 expression in the classification of non-Hodgkin's lymphomas: a morphometric and double-immunostaining study. AB - The proliferation of reactive and neoplastic cells was retrospectively assessed in 92 cases of non-Hodgkin's lymphoma by morphometry using a double immunoenzymatic technique including surface markers and the monoclonal antibody Ki-67. The findings were compared with the histological diagnosis. The overall Ki 67 positivity is not always a good measure of the corresponding corrected values and therefore we recommend that a correction should be made for the total number of complementary lymphocytes in the tumour. Taking the macrophages and the Ki-67 positivity of the reactive cells into account does not generally add any information. There was no difference in reactive cell content between follicular (counted within follicles) and diffuse lymphomas within the tumour areas. The value of the group mean for low-grade follicular (nodular) lymphomas was significantly higher than that of diffuse low-grade lymphomas, but not significantly different from that of intermediate-grade lymphomas. High-grade lymphomas exhibited significantly greater Ki-67 positivity than those of intermediate grade. In 76% of the cases there was significant agreement between malignancy grade (low/intermediate malignant versus high malignant) at 45% corrected Ki-67 counts. PMID- 1737623 TI - Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease. AB - Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse. PMID- 1737624 TI - Frequent expression of haemopoietic and non-haemopoietic antigens by neoplastic plasma cells: an immunohistochemical study using formalin-fixed, paraffin embedded tissue. AB - There is increasing evidence that neoplastic plasma cells express various haemopoietic and non-haemopoietic antigens. Since this issue could raise problems in diagnostic histopathology, we have investigated 51 cases of multiple myeloma (plasmacytoma) systematically with a broad panel of antibodies applicable on paraffin-embedded and mildly decalcified tissue. In approximately 90% of the cases the neoplastic plasma cells reacted with at least one antibody detecting haemopoietic antigens: MB2 (75%), DF-T1/CD 43 (59%), UCHL1/CD 45RO (47%), Ki-B3 (41%), anti-LCA/CD 45 (40%), L26/CD 20 (26%), 4KB5/CD 45RA (18%), Ber H2/CD 30 (10%), anti-neutrophil elastase (4%), anti-Leu-7/CD 57 (8%), Dako-M1/CD 15 (2%), KP1/CD 68 (2%) and anti-glycoprotein IIIa (2%). In approximately 70% of the cases the cells reacted with antibodies against non-haemopoietic antigens: anti epithelial membrane antigen (65%), BMA120 (53%), anti-vimentin (44%), anti-pan cytokeratin/KL1 (8%), anti-carcino-embryonic antigen (6%) and HMB45 (6%). Lack of awareness of the frequent expression of both haemopoietic and non-haemopoietic antigens by neoplastic plasma cells could lead to mis-diagnosis of plasmacytomas as malignant lymphomas or even as carcinomas or sarcomas. PMID- 1737625 TI - Localized deposition of amyloid in articular cartilage. AB - The frequency, nature and tissue distribution of localized amyloid deposits in articular cartilage of young and elderly patients, with and without evidence of arthritic disease, was determined. Localized amyloid deposits in articular cartilage were not found in young patients with osteoarthritis of the hip or chondromalacia/osteoarthritis of the patella. However, in elderly patients with osteoarthritis of the hip, amyloid deposits were commonly found, although at no greater frequency than in elderly patients with no evidence of arthritis. Amyloid deposits were commonly present (in 95% of cases) in osteoarthritis of the knee joint and in the articular cartilage of all joints containing pyrophosphate deposits. Similar deposits of amyloid were also found in the articular cartilage of 40-45% of rheumatoid joints. These findings indicate that localized amyloid deposits in the articular cartilage are largely age-related and not due to specific pathological alterations affecting articular cartilage. PMID- 1737626 TI - An assessment of involucrin as a diagnostically useful immunohistochemical marker in lung tumours. AB - A previous report has described involucrin as a specific immunohistochemical marker of squamous differentiation in lung carcinomas. The aim of our study was to examine the expression of this antigen in a wide variety of lung tumours, with particular attention to its potential value in the typing of biopsy specimens. We found that immunostaining for involucrin was common in squamous carcinomas but was also found in adenocarcinomas, adenosquamous carcinomas, large cell carcinomas and carcinosarcomas. Small cell carcinomas, carcinoid tumours and mesotheliomas were negative. Contrary to previous claims, this marker appears to have little diagnostic utility in the typing of lung tumours. PMID- 1737627 TI - Carcinoma of the thyroid at a young age--a review of 23 patients. AB - Twenty-three children and adolescents with thyroid carcinoma who were 20 years old or younger at the time of initial treatment were followed for a mean time of 9.5 years. Of the tumours, 21 were papillary and two follicular carcinomas. The majority (91%) of the 23 cases showed extra-thyroidal extension of the tumour. An association with chronic thyroiditis was observed in 30% of the cases. There was no history of irradiation of the head and neck in any patients. Relapse occurred in eight patients, lung metastases in two and local recurrences in six; one patient died from lung metastases 3 months after initial treatment. Male patients, advanced stage of tumour, less differentiated histological features and DNA aneuploidy were associated with a higher frequency of relapse. The prognosis of thyroid carcinomas in children and adolescents is not so good as is generally believed. PMID- 1737628 TI - Psammomatous melanotic schwannoma arising in the dermis in a patient with Carney's complex. PMID- 1737629 TI - Silverworker's finger: an unusual occupational hazard mimicking a melanocytic lesion. PMID- 1737630 TI - Intrathoracic schwannoma of the vagus nerve. PMID- 1737631 TI - Primary malignant melanoma of the oesophagus. PMID- 1737632 TI - Large cell lymphoma with fibrillary matrix. PMID- 1737633 TI - Mixed cloacogenic carcinoma of male urethra. PMID- 1737634 TI - Overwhelming septicaemia due to Streptococcus pneumoniae: unexpected autopsy findings. PMID- 1737635 TI - Tumour phase of mycosis fungoides in the tongue. PMID- 1737636 TI - Quantitative differentiation of the haptoglobin-related gene product from haptoglobin in human plasma: a possible test for tumor-associated antigen. AB - The haptoglobin-related gene product (HGRP) having greater than 90% sequence homology with plasma haptoglobin, has recently been implicated as a tumor maker of recurrent breast cancer. Therefore, availability of a monoclonal antibody which is specific to the HGRP and ensuing ELISAs to quantitate the HGRP without cross-reactivity with plasma haptoglobin will allow determination of the clinical value of the HGRP in human plasma under various pathophysiological conditions. A peptide representing the first 34 residues of the N-terminal portion of the HRGP was synthesized and conjugated to keyhole limpet hemocyanin (KLH) to immunize Balb/c mice. Hybrid clones that produced specific antibodies to HRGP were screened with the same peptide but conjugated to bovine serum albumin (HRGP-BSA). From 12 hybridoma clones that recognized HGRP-peptide, we obtained one IgM producing clone (27.5) by limiting dilution technique that selectively reacted with HGRP-peptide with minimal cross-reactivity with haptoglobin. Using a separate monoclonal antibody, clone 21.7, which is directed to the alpha subunit of haptoglobin, we developed an enzyme-linked immunosorbent assay (ELISA) to determine the quantities of the HGRP in human plasma, which will allow assessment of HGRP as a clinical marker of malignancy. PMID- 1737637 TI - Rapid isolation of immunoglobulin variable genes from cell lysates of rat hybridomas by polymerase chain reaction. AB - The isolation of the rearranged immunoglobulin genes from a hybridoma cell line, which is a prerequisite for the construction of a recombinant antibody, can easily be achieved by polymerase chain reaction. Here we demonstrate that this method, which was originally described for cloning murine immunoglobulin genes from cDNA, is also applicable for rat genes. We show that the procedure also works with crude cell lysates as starting material, thereby greatly reducing the time required for sample preparation. In addition we have sequenced the nonfunctional heavy chain variable gene of the fusion partner X63Ag8.653, which was readily amplified from our hybridoma cells, and whose sequence has been so far unknown. PMID- 1737638 TI - Chicken antibodies: a tool to avoid interference by human anti-mouse antibodies in ELISA after in vivo treatment with murine monoclonal antibodies. AB - Human anti-murine antibodies (HAMA) can be found in serum of many patients who have received murine monoclonal antibodies for diagnosis or therapy. These antibodies are known to give false positive results in sandwich-type assays (e.g. ELISA or RIA). This interference problem will increase in the future as more patients are treated with murine monoclonal antibodies in vivo. HAMA can also be found in sera from patients that has not been treated with monoclonal antibodies. In this work we have studied the interference of HAMA in sandwich ELISAs containing antibodies from different species. HAMA, present in the sample, may react both with the capture antibody and the detection antibody in these assays to give a false positive reaction. HAMA did not react with chicken IgG, and if one of (or both) the capture and detection antibody was of avian origin, the interference of HAMA in sandwich assays could be avoided. PMID- 1737639 TI - Enhanced transfection of a bacterial plasmid into hybridoma cells by electroporation: application for the selection of hybrid hybridoma (quadroma) cell lines. AB - A procedure was investigated to transduce a bacterial plasmid containing a specific drug resistance marker (pSV2-neo), into a hybridoma cell line using electroporation. The effect of several buffers and the form of plasmid DNA (circular or linearized) on the stable transfection frequency were examined. When complete cell culture medium (DMEM) was used as electroporation buffer, we observed a two-fold increase in post-pulse viability and a ten- to thirty-fold increase in the transfection frequency of pSV2-neo, as compared with HEPES buffered 0.15 M sodium chloride. Supplementing DMEM with fetal bovine serum (DMEM + FBS) had some beneficial effect on post-pulse viability of the cells after electroporation, but did not markedly increase stable transfection frequency as compared with DMEM alone. Furthermore, with DMEM + FBS, the intact plasmid was transfected as effectively as linearized PSV2-neo. However, when using HEPES buffered saline, the transfection frequency of pSV2-neo increased two-fold after linearization as compared with intact plasmid. The drug resistance was used successfully as a marker for the selection of hybrid hybridoma (quadroma) cell lines after fusing two different hybridoma cell lines, producing anti-fibrin and anti-plasminogen activator antibodies respectively. The quadroma cells produced bispecific antibodies that are capable of accumulating plasminogen activator on a fibrin surface. PMID- 1737640 TI - Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgG1 subclass. AB - A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the CK-2 alpha subunit in immunoblots from tissue extracts. An ELISA detection test was also established which also allows the identification of the CK-2 alpha subunit. PMID- 1737641 TI - Production of novel monoclonal antibodies against rabbit platelet factor four. AB - Ten hybridomas producing monoclonal antibodies (Mabs) against rabbit platelet factor 4 (PF4) were obtained from the fusion of splenocytes from mice immunized with purified rabbit PF4 and NSO mouse myeloma cells. When the reactivities of these monoclonal antibodies were determined by enzyme-linked immunosorbent assay and immunoblotting with human and rabbit PF4, they showed a high degree of specificity. Only one Mab recognized an epitope common to the human and rabbit molecules, the other nine reacted only with the rabbit protein. All the antibodies recognized, in crude platelet lysates, a band that comigrates with the purified PF4 protein. None of these antibodies cross-reacted with major rabbit or human platelet-poor plasma proteins. The significance of the Mabs in immunological and physiological studies is discussed. PMID- 1737642 TI - Development and characterization of a panel of monoclonal antibodies against the novel subtilisin-like proprotein processing enzyme furin. AB - Monoclonal antibodies were raised against the recently discovered subtilisin-like proprotein processing enzyme furin. As immunogen, a bacterially expressed hybrid protein was used which consisted of glutathione S-transferase fused to almost the entire human furin protein. Ten monoclonal antibodies were obtained and these could be divided into four categories on the basis of their reactivity towards a number of bacterially expressed hybrid proteins, each of which contained a different portion of human furin. Four of the monoclonal antibodies did not recognize mouse furin. All monoclonal antibodies were tested for their applicability in Western blot and immunofluorescence analysis. Western blot analysis was performed with COS-1 cells in which biologically active forms of human and mouse furin were expressed transiently under control of the SV40 late promoter. This approach was necessary, since physiological levels of fur gene encoded proteins appeared to be very low. In cells transfected with human or mouse fur cDNA, a protein of about 100 kDa and a doublet of about 90 kDa could be detected with most of the monoclonal antibodies. Some of these antibodies appeared to be also reactive in immunofluorescence analysis of transfected COS-1 cells. PMID- 1737643 TI - Immunoglobulins secreted by a hybrid-hybridoma: analysis of chain assemblies. AB - In addition to the bispecific antibody, the hybrid-hybridoma 28.19.8 secretes antibodies monospecific for carcinoembryonic antigen (CEA) and antibodies monospecific for vinca alkaloids. By exhaustive affinity purification, the immunoglobulins isolated by Protein A chromatography from ascitic fluid have been fractionated into four populations, three of which are immunoreactive. Studies on these fractions by FPLC, SDS-PAGE, and a variety of ELISAs have shown that seven of the ten possible combinations of heavy and light chains exist as immunoreactive forms. The results suggest that the other three inactive combinations are also secreted by the hybrid-hybridoma. PMID- 1737644 TI - Influence of somatic cell hybridization and human serum on the generation and stability of human hybridomas. AB - We describe an approach that allows the generation of stable hybridomas secreting antigen specific human IgG antibodies with an efficiency comparable to that of the generation of IgM and IgA secreting hybridomas. This was achieved by evaluating means to increase the frequency of human hybridoma formation and the stability of the generated hybridoma cells when subjected to conditions for large scale growth. To this end, we generated new fusion lines with an increased human DNA content and modified the culture system. However, the application of these new fusion lines primarily resulted in unstable giant cells. As a consequence, we evaluated whether the viability of newly formed hybrids between existing fusion lines and lymphoblastoid cell lines might be improved. In an attempt to provide as many components necessary for the growth of antibody secreting hybridomas as possible, we propagated fused cells in medium supplemented with human serum. Our results show that with this approach the frequency of initially growing hybrids was significantly increased. Furthermore, only in culture medium supplemented with human serum was it possible to obtain stable IgG secreting clones. PMID- 1737645 TI - Endothelium-derived contracting factors. AB - The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation. PMID- 1737646 TI - Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries. AB - In cultured endothelial cells, endothelin is produced after stimulation with angiotensin II. The effects of angiotensin II and endothelin-1 on vascular sensitivity to norepinephrine were studied in perfused rat mesenteric resistance arteries. Expression of endothelin messenger RNA (mRNA) was determined in endothelial cells obtained from the mesenteric circulation. Perfusion (5 hours) of the arteries with angiotensin II (10(-7) M) potentiated contractions in arteries with endothelium induced by norepinephrine in spontaneously hypertensive rats but not Wistar-Kyoto rats. The potentiation was inhibited by phosphoramidon and an endothelin antibody. Short-term stimulation (1 hour) with angiotensin II did not cause the potentiation. Stimulation with angiotensin I (10(-7) M; 5 hours) caused a potentiation prevented by captopril. In endothelial cells collected from the mesenteric arterial bed of spontaneously hypertensive rats, endothelin-specific mRNA was constitutively expressed, and the level of endothelin transcripts was increased by angiotensin II (10(-7) M). Threshold concentrations of exogenous endothelin-1 potentiated contractions induced by norepinephrine in arteries with and without endothelium of spontaneously hypertensive rats but not Wistar-Kyoto rats. Thus, angiotensin II stimulates the endothelial production of endothelin in situ and therapy potentiates contractions to norepinephrine in mesenteric resistance arteries of spontaneously hypertensive rats. This suggests that vascular endothelin production acts as an amplifier of the pressor effects of the renin-angiotensin system that may play an important role in hypertension. PMID- 1737647 TI - Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension. AB - We investigated the role of kinins in the acute depressor effect of captopril and ramiprilat in spontaneously hypertensive rats. Since the vasodepressor action of kinins may be linked to the generation of prostaglandins and endothelium-derived relaxing factors, we also investigated the role of prostaglandins and nitric oxide in the blood pressure reduction caused by angiotensin converting enzyme inhibitors. To this end, we contrasted the hypotensive effects of captopril (10 mg/kg i.v.), ramiprilat (2 mg/kg i.v.), and the angiotensin II antagonist DuP 753 (30 mg/kg i.v.) in spontaneously hypertensive rats with and without pretreatment with a kinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg trifluoroacetic acid) (200 micrograms/kg/min i.v.), an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine) (15 mg/kg + 10 mg/kg/hr i.v.), or an inhibitor of prostaglandin synthesis (indomethacin) (10 mg/kg i.v.). The kinin antagonist did not affect blood pressure in spontaneously hypertensive rats but did attenuate the hypotensive effect of captopril and ramiprilat; the kinin antagonist did not minimize the depressor action of DuP 753. The nitric oxide synthesis inhibitor increased blood pressure in spontaneously hypertensive rats and attenuated the hypotensive effect of captopril, ramiprilat, and DuP 753, but it did not impede the hypotensive effect of sodium nitroprusside. Pretreatment of hypertensive rats with indomethacin did not modify the acute hypotensive effect of ramiprilat or captopril. These data suggest a contribution of endogenous kinins and nitric oxide to the acute antihypertensive effect of captopril and ramiprilat in spontaneously hypertensive rats and of nitric oxide to the hypotensive effect of DuP 753. PMID- 1737648 TI - Angiotensin II-induced changes in guanine nucleotide binding and regulatory proteins. AB - Systemic infusion of angiotensin II, a potent agonist, using doses that are initially subpressor, eventually produces sustained blood pressure elevation and reductions in glomerular capillary ultrafiltration coefficient characterized by enhanced signal transduction to angiotensin II and other agonists. In this setting, there is a significant increased affinity of angiotensin II binding to smooth muscle and glomerular mesangial receptors and enhanced sensitivity and magnitude of angiotensin II-induced decrements in cyclic AMP. Since G proteins are important modulators of binding and signal transduction, the present studies were designed to test the hypothesis that differences in the relative amounts of G proteins may be present and have accounted for differences observed. G proteins were identified and quantitated by isoelectric focusing/sodium dodecyl sulfate polyacrylamide gel electrophoresis, radiolabeling in the presence of activated toxins with [gamma-32P]NAD+, immunoprecipitation, and immunoblotting. A 168% and 465% increase in pertussis toxin-catalyzed ADP ribosylation of alpha 40-41 was found in angiotensin II-treated groups over control groups for glomerular and mesenteric membranes, respectively. Immunoblotting revealed a 250% and 35% increase in the levels of the Gi isoforms alpha i-2 and alpha i-3, respectively, and a decrease of 53% in alpha i-1 from the angiotensin II-treated group. No differences were observed in cholera toxin labeling or immunoblotting of Gs. These results demonstrate multiple mechanisms whereby angiotensin-induced signal transduction can be modulated involving both the receptors and G proteins. These observed differences in G proteins in systemic and renal vasculature accompanying angiotensin II infusion suggest the possibility of a regulatory role in the pathophysiology of angiotensin II-induced hypertension and renal disease. PMID- 1737649 TI - Enhanced myogenic responsiveness of renal interlobular arteries in spontaneously hypertensive rats. AB - We recently demonstrated that the interlobular artery (ILA) constricts in response to elevating renal arterial pressure (RAP), suggesting that the ILA contributes to renal autoregulation. In the present study, we examined the segmental myogenic responsiveness of the ILA in kidneys from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The tapered nature of the ILA allowed us to characterize the regional responsiveness, using the basal diameter to define segments as either proximal (greater than 60 microns), intermediate (40 60 microns), or distal (less than 40 microns). At 80 mm Hg, segmental diameters were similar in WKY and SHR arteries (proximal, 76.0 +/- 3.1 versus 71.6 +/- 3.5 microns; intermediate, 48.2 +/- 1.4 versus 48.1 +/- 1.7 microns; distal, 30.7 +/- 0.9 versus 27.9 +/- 1.3 microns for WKY and SHR, respectively). In both strains, intermediate and distal segments exhibited graded reductions in diameter as RAP was elevated, whereas proximal segments did not. Pressure-induced decrements in the diameters of distal ILA segments were similar in WKY (-24 +/- 2%) and SHR ( 20 +/- 2%; p greater than 0.1). The intermediate ILA of SHR exhibited an augmented myogenic responsiveness, constricting at lower RAP levels and exhibiting greater maximal decrements in diameter at 180 mm Hg (i.e., -19 +/- 2% and -12 +/- 2% for SHR and WKY, respectively; p less than 0.05). Nifedipine (1.0 microM) reduced pressure-induced vasoconstriction of intermediate and distal ILA segments by 56 +/- 11% and 79 +/- 7%, respectively, in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737650 TI - Mechanism of neurally induced monkey mesenteric artery relaxation and contraction. AB - Physiological importance in vasodilator innervation alleviating noradrenergic neurogenic vasoconstriction has not been clarified. Isolated monkey mesenteric artery strips denuded of the endothelium responded to nerve stimulation by electrical pulses or nicotine with a contraction, which was potentiated by Ng nitro-L-arginine, a nitric oxide synthesis inhibitor, but not by the D enantiomer. The potentiation was abolished by L-arginine. NG-Nitro-L-arginine did not potentiate the response to exogenous norepinephrine nor did it increase the release of [3H]norepinephrine from adrenergic nerves electrically stimulated. The contraction was reversed by treatment with phentolamine and guanethidine to a relaxation, which was abolished by NG-nitro-L-arginine. The inhibition was reversed by L- but not D-arginine. The relaxant response was not influenced by atropine, timolol, or indomethacin. These findings strongly suggest the importance of reciprocal nitric oxide-related (nitroxidergic) vasodilator and noradrenergic vasoconstrictor innervation in the regulation of monkey arterial tone. PMID- 1737651 TI - Control of the erythrocyte free Ca2+ concentration in essential hypertension. AB - Since Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca2+]i) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca2+]i was measured by using the fluorescent Ca2+ chelator fura-2. Red blood cell [Ca2+]i was increased in hypertensive compared with normotensive subjects in the whole population and further increased when hypertensive were compared with age-matched normotensive subjects. An inverse relation between age and [Ca2+]i was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca2+]i values were associated with a reduced erythrocyte deformability. The initial rate of 45Ca2+ uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca2+ concentration was elevated from 1 to 2 mmol/l, [Ca2+]i increased by 16 +/- 4% (p less than 0.03) in red blood cells from both groups, thus maintaining a significant difference between hypertensive and normotensive subjects. Under these conditions, the addition of 10(-7) mol/l nicardipine, a dihydropyridine Ca2+ antagonist, decreased [Ca2+]i by 15 +/- 4% (p less than 0.05) and 7 +/- 5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca2+]i observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca2+]i. In the presence of 5 mumol/l W7, a calmodulin antagonist, [Ca2+]i increased significantly only in erythrocytes from hypertensive patients (26 +/- 6%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737652 TI - Magnesium supplementation prevents the development of alcohol-induced hypertension. AB - The effect of chronic alcohol administration on blood pressure was investigated in 7-week-old Wistar rats. Tail-cuff blood pressure was significantly higher in rats who received 15% ethanol in drinking water than in control rats. Intracellular free calcium concentration of lymphocytes was increased, while magnesium concentration of erythrocyte, aorta, and skeletal muscle and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) were decreased in alcohol-induced hypertensive rats but not in control rats. Extracellular fluid volume was also increased in alcohol-administered rats. Oral magnesium supplementation (1% MgO in rat chow) attenuated the development of alcohol induced hypertension accompanied by increased magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos and decreased intraerythrocyte sodium concentration. Norepinephrine half-life time of the heart and spleen was also increased in magnesium-supplemented rats. Blood pressure significantly correlated positively with intracellular calcium concentration and extracellular fluid volume, negatively with magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos. These results suggest that increased intracellular calcium, which was partly due to magnesium depletion and suppressed sodium pump activity, and expanded body fluid volume had a possible role in the development of alcohol-induced hypertension. It is also suggested that oral magnesium supplementation had a hypotensive effect on alcohol-induced hypertension possibly through decreased intracellular sodium concentration caused by an activation of sodium pump and decreased sympathetic nervous activity. PMID- 1737653 TI - Aftereffects of exercise on regional and systemic hemodynamics in hypertension. AB - Several studies have indicated that a single bout of physical exercise induced a significant antihypertensive effect during the hours after the activity. However, little information is presently available on the underlying hemodynamic changes. We examined 13 essential hypertensive patients and nine normotensive subjects in a randomized, crossover study design during 3 hours after a 30-minute period of upright leg cycling at 50% of peak aerobic capacity and during 3 hours after a 30 minute control period of rest. Blood pressure, heart rate, cardiac output, total peripheral resistance, and regional vascular resistance in the forearm as well as venous plasma catecholamine concentrations were measured repeatedly. After exercise, systolic (-11 +/- 2 mm Hg) and diastolic (-4 +/- 1 mm Hg) blood pressures, total peripheral resistance (-27 +/- 5%), forearm vascular resistance (-25 +/- 6%), and plasma norepinephrine levels (-21 +/- 7%) were significantly (p less than or equal to 0.05) decreased, and cardiac output was increased (+31 +1- 8%) compared with control in hypertensive subjects. In contrast, in normotensive subjects blood pressure, forearm vascular resistance, and plasma norepinephrine were unchanged, and systemic hemodynamics changed to a lesser extent than in hypertensive subjects after exercise. It is concluded that a decrease in regional vascular resistance in skeletal muscles and possibly in the skin in hypertensive patients may contribute importantly to the antihypertensive effect of prior exercise. A decreased sympathetic nervous activity, as seen from lower plasma norepinephrine levels, may be involved in this effect. PMID- 1737654 TI - Genetic influences on the urinary excretion of aldosterone in children. AB - Several studies have shown an inverse relation between blood pressure and plasma aldosterone levels. Since blood pressure is in part genetically regulated, we looked for evidence that genetic factors might also affect aldosterone production. The nocturnal urinary excretion rate was used to estimate aldosterone production, and electrolyte excretion rates were used to estimate sodium and potassium intakes. Studies were carried out in monozygotic (MZ) (n = 37 pairs) and dizygotic (DZ) (n = 26 pairs) twins, aged 6-17 years. Both groups of twins were white. The intraclass correlation coefficient for aldosterone excretion was 0.686 (p = 0.0001) for MZ twins, and 0.290 (p = 0.079) for DZ twins, indicating high heritability for the aldosterone excretion rate. In a second study, we looked for a racial effect on the genetic regulation of aldosterone excretion. Siblings from both black and white families (72 black siblings and 157 white siblings) were selected from an ongoing longitudinal study. Mean values for nocturnal aldosterone excretion, rates measured every 6 months over 1.5-3.5 years, were used in the analysis. The intraclass correlation coefficient for aldosterone excretion, adjusted for sodium and potassium excretion, was 0.510 (p = 0.001) for black siblings and 0.087 (p = 0.228) for white siblings, indicating a strong familial aggregation for aldosterone excretion in black children. In conclusion, studies in twins showed that regulation of urinary aldosterone excretion in children is determined partially by genetic factors. A familial component affecting the aldosterone excretion rate appears to be much stronger in blacks than in whites. PMID- 1737655 TI - Frederick Akbar Mahomed. AB - Frederick Akbar Mahomed was an Englishman of mixed Indian and Irish descent who made substantial contributions to the study of high blood pressure in a short professional life from 1872 to 1884. He was strongly influenced by the previous work of Richard Bright on kidney disease at his own hospital (Guy's Hospital in London) and by the contemporary pathological studies of Gull and Sutton on arteriolar changes in persons with high blood pressure. In detailed clinical studies, he separated chronic nephritis with secondary hypertension from what we now term essential hypertension. He described the constitutional basis and natural history of essential hypertension and pointed out that this disease could terminate with nephrosclerosis and renal failure. His clinical studies were done without the benefit of a sphygmomanometer but with the aid of a quantitative sphygmogram that he had initially developed while a medical student. He described characteristic features of the pressure pulse in patients with high blood pressure and in persons with arteriosclerosis consequent on aging. These pressure wave changes have recently been verified and explained. He contributed to a number of other advances in medical care, including blood transfusion and appendectomy for appendicitis. He initiated the Collective Investigation Record for the British Medical Association; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials. Mahomed died from typhoid fever, almost certainly contracted from one of his patients, at age 35 at the height of his career. PMID- 1737656 TI - "White coat" hypertension. PMID- 1737657 TI - The Georgia Centenarian Study. PMID- 1737658 TI - Personality, life events and coping in the oldest-old. AB - This paper compares older adults in their sixties, eighties, and 100s on personality, experience of life events, and coping. A secondary goal was to test a structural model of adaptation. Participants (165) filled out a personality inventory, life-event lists, and coping and mental health measures. Results revealed differences in personality: centenarians scored higher on dominance, suspiciousness, and imagination. While centenarians scored lower on active behavioral coping than other age groups, they used cognitive strategies when coping with health and family events. Results from the structural equation model indicated that extraversion and anxiety predicted morale and mental health. PMID- 1737659 TI - The influences of cognitive resources on adaptation and old age. AB - In the Georgia Centenarian Study, cognitive resources were estimated by fluid and crystallized intelligence, acquisition and retrieval of new information, retrieval of familiar information, and problem-solving ability in community dwelling and nondemented adults ranging from sixty to one hundred plus years of age. Five clusters of results were found: 1) cognitive performances were lower for the older cohorts; 2) when cognitive activities were dependent on everyday experiences, no age-related problem-solving decline was found; 3) physical health and mental health can significantly influence cognitive performances; 4) cognitive and personality factors can combine to account for a larger amount of adaptation variance than can be accounted for by either of the factors alone; and 5) individuals with a high level of intelligence and affect sustain their instrumental activities of daily living. Cognitive resources were an important contributor to successful adaptation for the oldest-old. PMID- 1737660 TI - Religiosity and adaptation in the oldest-old. AB - Previous research has yielded mixed results with respect to the relationship between religiosity and adaptation in older adults. Most studies show that religiosity is stable over the life span, but that religiosity may or may not be related to such factors as physical and mental health, life satisfaction, and coping. This study adds to earlier investigations by including centenarians among the sample. The preliminary results of this research project support earlier findings that religiosity does not change significantly as one ages, although there is a trend in the results that suggests otherwise. The results also indicate a significant relationship between religiosity and physical health but no significant relationship between religiosity and mental health and life satisfaction. Religiosity and coping are strongly related, and there is the suggestion that religious coping mechanisms might be more important in the oldest old. PMID- 1737661 TI - Nutritional patterns of centenarians. AB - This study compares the dietary patterns of centenarians (n = 24) with elderly adults in their sixties (n = 54) and eighties (n = 47). Compared to the younger cohorts, centenarians consumed breakfast more regularly, avoided weight loss diets and large fluctuations in body weight, consumed slightly more vegetables, and relied on their doctor and family more than on the news media for nutrition information. On the other hand, centenarians were less likely to consume diets low in fat and to comply with nutritional guidelines designed to reduce the risk of chronic disease. Elderly black men consumed diets higher in sweets and fat compared to black women and white men and women. Nearly three times as many blacks expressed the desire to eat more nutritiously. High nutrition risks, particularly in blacks, were associated with lower physical and mental health and impaired activities of daily living. PMID- 1737662 TI - The Georgia Centenarian Study: comments from friends. PMID- 1737663 TI - Anomalous coronary arteries: angiographic findings in 80 patients. AB - Among 13010 adults who underwent coronary arteriography, 80 (0.61%) patients had a total of 83 anomalous coronary arteries. Thirty-three (41%) of the patients were of Hispanic origin, while out of the entire population studied 30% were Hispanic. The right coronary artery was the most common anomalous vessel. It was identified in 50 (62%) patients, arising in 35 from the left aortic sinus, in 14 from the posterior sinus, and in 1 from the left coronary artery. An anomalous circumflex artery was recognized in 22 (27%) patients. Nine (11%) patients presented an anomalous left anterior descending artery, 1 patient an anomalous left main coronary artery, and another an anomalous septal perforator artery. Twenty-three (29%) patients had concomitant congenital heart abnormalities, most commonly. bicuspid aortic valve and mitral valve prolapse. In each of 5 patients with complex congenital heart disease the course of the anomalous vessel could have interfered with a surgical procedure. In 4 cases anomalous coronary arteries were associated with either anomalous systemic venous circulation or anomalous cardiac veins. In 5 (6%) patients only, the anomalous coronary artery was solely responsible for a clinical event. Coronary atherosclerosis of the anomalous arteries was found in 28% of the patients, while the overall incidence of the disease in this series was 65%. Thus, anomalous coronary arteries are associated with a high incidence of congenital heart diseases, but do not appear to be associated with an increased risk for development of coronary atherosclerosis. The angiographic recognition of these vessels is important in patients who undergo coronary angioplasty or cardiac surgery. Variations in the frequency of congenital coronary anomalies as reported herein may be attributed to a genetic background. PMID- 1737664 TI - Resection of right atrial lymphoma in a patient with AIDS. AB - Although cardiac problems are common in acquired immunodeficiency syndrome, there is limited experience with heart surgery in this group of patients. We report a case in which a right atrial lymphoma was resected to alleviate tricuspid valve obstruction in a patient with AIDS. The patient did well for approximately 7 months. At that time, he developed multiple complications of AIDS and deteriorated rapidly; he died 8 months after operation. Cardiac surgery can be successfully performed in AIDS patients. However, the late outcome is compromised by the nature of the underlying viral infection. PMID- 1737665 TI - Adverse effects of epinephrine in patients with advanced left ventricular dysfunction: analysis of ventriculo-arterial coupling. AB - We examined the response of ventriculo-arterial coupling to epinephrine in 19 patients with normal left ventricular function and with left ventricular dysfunction of various degrees using a conductance catheter. They were divided into three groups: group I, seven patients without left ventricular wall motion abnormality; group II, six patients with ejection fraction of 45-60%; group III, six patients with ejection fraction of 28-40%. Changes in the slope of the end systolic pressure-volume relationship (end-systolic elastance), the effective arterial elastance, the ratio of effective arterial elastance to end-systolic elastance and the ventricular work efficiency during administration of two different doses of epinephrine (0.05 and 0.1 micrograms/kg/min) were compared among the three groups. At baseline there were no significant differences among the three groups in the ratio of effective arterial elastance to end-systolic elastance, or ventricular work efficiency. At the lower dose of epinephrine, the mean ratio of effective arterial elastance to end-systolic elastance decreased and the mean ventricular work efficiency increased in any groups. At the higher dose of epinephrine the mean ratio of effective arterial elastance to end systolic elastance further decreased and the mean ventricular work efficiency further increased in groups I and II. However, the mean ratio of effective arterial elastance to end-systolic elastance did not decrease but the mean ventricular work efficiency even decreased in group III. Thus, in patients with advanced left ventricular dysfunction, even a high dose of epinephrine does not modulate the ventriculo-arterial coupling to increase ventricular work efficiency. PMID- 1737666 TI - Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up. AB - Sixteen patients (12 male and 4 female, age 2-46 years) with endomyocardial biopsy-proven myocarditis were prospectively evaluated with immunosuppressive therapy including azathioprine and prednisolone in addition to other standard measures. Patients were either in NYHA class IV (n = 12) or class III (n = 4). Twelve patients showed improvement and the remaining 4 continued to deteriorate: 2 died at 1 and 2 months after therapy and the other 2 were lost to follow-up after 4-6 weeks of therapy. Three of the 12 patients who showed significant improvement, after sudden omission of therapy (at 8 weeks, 6 and 8 months) worsened and died. One patient who showed significant improvement died suddenly after 9 months of therapy while playing football. The remaining patients have shown significant clinical and haemodynamic improvement with normalization of myocardial morphology. Serial haemodynamic studies revealed a significant fall in cardiothoracic ratio (before: 62.3 +/- 4.7%; 3 months: 55.1 +/- 3.1%, P less than 0.0001; 6-12 months: 50.6 +/- 1.5%, P less than 0.0001), mean pulmonary artery pressure (before: 34.3 +/- 13.05 mm; 3 months: 20.4 +/- 8.71 mm, P less than 0.01; 6-12 months: 20.0 +/- 2.75 mm, P less than 0.01) and mean pulmonary artery wedge pressure (before: 26.0 +/- 9.07 mm; 3 months 14.0 +/- 5.63 mm, P less than 0.001; 6-12 months: 13.2 +/- 4.57 mm, P less than 0.001). The left ventricular ejection fraction improved from 24.3 +/- 8.36% to 35.8 +/- 9.72% (P less than 0.001) at 3 months and 49.8 +/- 18.2% (P less than 0.0001) at 6-12 months of therapy. Two patients have been subsequently lost to follow-up whereas the remaining 6 patients are on follow-up for 1-4 years after therapy and are doing fine. Our uncontrolled observations suggest that immunosuppressive therapy may be useful in patients with inflammatory myocarditis. PMID- 1737667 TI - Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina. AB - The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway. PMID- 1737668 TI - Circadian variation of ventricular tachycardia in patients with coronary arterial disease. AB - Sudden cardiac death and ischaemic cardiac events occur in a circadian pattern. Because ventricular tachycardia is thought to play an important role in sudden cardiac death, the episodes of spontaneous ventricular tachycardias (greater than 3 consecutive beats) (n = 1314) were analysed from 24-hour long term electrocardiographic recordings in 34 patients with coronary arterial disease to determine whether circadian rhythm exists in spontaneous ventricular tachycardia. Twelve patients had suffered cardiac arrest, four patients had a history of syncope, and palpitation was the indication for electrocardiographic recordings in eighteen patients. Analysis using chronobiologic single cosinor method showed a significant circadian variation in the occurrence of ventricular tachycardia episodes with the peak occurring at 6 a.m. Similar circadian rhythm was also observed in the occurrence of the longest episode of ventricular tachycardia. Ischaemic ST-segment depression preceded the longest ventricular tachycardia episode only in one patient. Thus, a circadian rhythm occurs also in spontaneous episodes of ventricular tachycardia, a finding which is similar to that in sudden cardiac death. PMID- 1737669 TI - Enhanced release of atrial natriuretic factor during exercise-induced myocardial ischaemia in patients after acute myocardial infarction. AB - To determine whether acute myocardial ischaemia induced by dynamic exercise can lead to changes in plasma levels of atrial natriuretic factor, we performed symptom-limited bicycle electrocardiographic tests in 20 males with recent acute myocardial infarction and in 8 control males. Ten patients developed exercise induced myocardial ischaemia and 10 patients did not. There were no significant differences between the two groups with regard to age, site of myocardial infarction, urinary sodium, atrial sizes, radionuclide left ventricular ejection fraction, workload, baseline and peak-exercise heart rate, baseline and peak exercise rate-pressure product, duration of exercise. Also baseline atrial natriuretic factor concentrations were similar in both groups (ischaemic patients: 34.51 +/- 15.73 pg/ml; nonischaemic patients: 27.17 +/- 8.74 pg/ml, NS), while peak-exercise atrial natriuretic factor concentrations were higher in patients with exercise-induced myocardial ischaemia (112.31 +/- 35.5 pg/ml) than in the others (80.46 +/- 23.43 pg/ml) (P less than 0.05). After 15 minutes of recovery, plasma atrial natriuretic factor levels were still raised only in the ischaemic patients (63.3 +/- 15.44 pg/ml, P less than 0.01), returning to baseline after 30 minutes in both groups. In control subjects, the behaviour of atrial natriuretic factor resembled that of the patients without exercise-induced ischaemia, with a significant increase at peak-exercise (from baseline levels of 23.1 +/- 10.5 pg/ml to peak-exercise levels of 91.3 +/- 14.5 pg/ml, P less than 0.0005) and a rapid return to baseline levels after 15 minutes of recovery (28.5 +/- 10.6 pg/ml, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737670 TI - Provocation of supraventricular tachycardias by an intravenous class I antiarrhythmic drug. AB - Antiarrhythmic drugs may aggravate or induce ventricular arrhythmia. The induction of a supraventricular tachycardia or its facilitation has rarely been reported. The purpose of the study was to know whether the potential for supraventricular proarrhythmic effect of a class Ia intravenous antiarrhythmic drug can be exposed during electrophysiologic study. Ajmaline was chosen because of its short duration of action. The protocol of the study consisted of an electrophysiological study and programmed atrial stimulation using 1 and 2 extrastimuli on driven rhythm and atrial pacing up to second-degree atrioventricular block. Then 1 mg/kg of ajmaline was injected and atrial pacing was performed 3 minutes after its injection. Supraventricular proarrhythmic effect of ajmaline was defined as the spontaneous occurrence of a supraventricular tachycardia or the facilitation of its induction. Seventy patients among 1955 presented a proarrhythmic effect: 63 developed a supraventricular tachyarrhythmia (atrial flutter, fibrillation, tachycardia) and 7 an atrioventricular reentrant tachycardia, either spontaneously (n = 23) or during atrial pacing (n = 47). Risk factors were identified in most patients: old age, underlying heart disease, history of spontaneous supraventricular tachycardia and/or induction of a supraventricular tachycardia by 2 extrastimuli on driven rhythm in the control state (34 patients), sinus node dysfunction (22 patients). Compared with patients without proarrhythmic supraventricular effect only the history of spontaneous supraventricular tachycardia and the existence of a sinus node dysfunction were significantly more frequent (P less than 0.05) in patients with proarrhythmic effect of ajmaline. In conclusion, the supraventricular proarrhythmic effect of intravenous ajmaline exists and is related both to the electrophysiologic characteristics of the drug and to the arrhythmia substrate. The results indicate that a supraventricular tachyarrhythmia may be induced by a class I antiarrhythmic drug. PMID- 1737671 TI - Immunohistochemical and histochemical profile of Aschoff bodies in rheumatic carditis in excised left atrial appendages: an immunoperoxidase study in fresh and paraffin-embedded tissue. AB - We have evaluated the nature of Aschoff cells within Aschoff bodies seen in 35 of 100 excised left atrial appendages from cases of rheumatic mitral stenosis who underwent closed mitral valvotomy. These were tested using a panel of monoclonal and polyclonal antisera by the indirect immunoperoxidase staining for leucocyte common antigen, macrophage, desmin, vimentin, alpha-1-antitrypsin, alpha-1 antichymotrypsin, lysozyme, acid phosphatase and nonspecific esterase. The Aschoff cell gave strong reactivity with monoclonal antisera to vimentin, macrophage and variable reaction with polyclonal antisera known to recognise macrophages/histiocytes in tissues, namely alpha-1-antitrypsin, alpha-1 antichymotrypsin and lysozyme. These were also strongly positive for acid phosphatase and nonspecific esterase. The Aschoff cell lacked affinity for desmin and only an occasional cell in 4 out of 20 and 6 out of 35 cases showed a weak reaction with myoglobin and leucocyte common antigen, respectively. Intense consistent reactivity with several histiocytic markers affirms the genesis of these cells from macrophages/histiocytes and not muscle cells; a controversy which must be laid to rest! PMID- 1737672 TI - Resolution of spontaneous echocardiographic contrast after percutaneous balloon mitral commissurotomy. PMID- 1737673 TI - Prenatal diagnosis of tetralogy of Fallot with absence of the leaflets of the pulmonic valve. AB - Tetralogy of Fallot with absence of the leaflets of the pulmonic valve is relatively rare. We describe the prenatal diagnosis of this malformation in two fetuses. The association between the agenesis of the arterial duct and absence of the valvar leaflets is discussed. The diagnosis of the syndrome in the presence of dilated and pulsatile pulmonic arteries is easy to make. It should allow early counselling and planning of early care after delivery. PMID- 1737674 TI - Preventable sudden death in patients receiving angiotensin converting enzyme inhibitors and loop/potassium sparing diuretic combinations. AB - Angiotensin-converting-enzyme inhibitors are frequently used in conjunction with diuretics in the treatment of congestive cardiac failure. We report two cases in which use of a proprietary combination diuretic containing a loop diuretic and potassium sparing agent with an angiotensin converting enzyme inhibitor was associated with hyperkalaemic cardiac arrest. Successful resuscitation from the arrest permitted elucidation of its mechanism. We believe that this outcome has not previously been reported, and emphasise the importance of electrolyte monitoring in patients receiving angiotensin converting enzyme inhibitors particularly if prescribed in addition to fixed combination proprietary diuretics. PMID- 1737675 TI - Aortic coarctation endarteritis and aneurysm: diagnosis by transoesophageal echocardiography. AB - A 17-year-old girl developed infective endarteritis, caused by Staphylococcus aureus, at the site of a previously undiagnosed aortic coarctation. Transoesophageal echocardiography revealed a clinically unsuspected false aneurysm. Foreknowledge of the presence of the aneurysm proved to be life saving when an acute deterioration required emergency surgery. PMID- 1737676 TI - Characteristics of transient myocardial ischaemia and acute occlusion in the immediate post-angioplasty period. AB - Holter monitoring was used to assess the incidence and characteristics of myocardial ischaemia immediately after successful coronary angioplasty in 24 patients. In 5 patients a total of 16 episodes of ST depression were recorded. All were asymptomatic but ranged from 4 minutes to over 20 hours in duration. These patients, however, made an uncomplicated recovery, as did 18 patients with no ischaemic episodes. In the remaining patient, initially labile, but then, fixed ST elevation, accompanied by chest pain occurred. Subsequent angiography demonstrated acute vessel occlusion. These labile ischaemic changes indicate that prior to complete occlusion the vessel may be in a dynamic state when antispasmodic and antithrombotic therapies may be of value. PMID- 1737677 TI - Isolated right ventricular infarction mimicking additional infero-posterior left ventricular infarction. AB - A case of isolated right ventricular infarction mimicking additional infero posterior left ventricular infarction on the surface electrocardiogram is presented. Gross dilatation of the right ventricle was probably responsible for the electrocardiographic findings. PMID- 1737678 TI - Balloon nitinol device: a new possibility for the fixation of balloons in large arteries. AB - We propose a balloon with nitinol needles for the closure of large vessels avoiding the risk of embolisation. To demonstrate the possibility of application, we utilised a prototype consisting of a polyurethane balloon with one nitinol needle which reached the shape for securing the balloon to the vessel wall after changing the temperature of the device. If further research and experimentation in animals are favorable, it will be possible for the interventional cardiologist to occlude large vessels and perhaps intracardiac shunts easily without danger of embolisation. PMID- 1737679 TI - Calcium intake in Western countries. PMID- 1737680 TI - Mupirocin in the treatment of impetigo. PMID- 1737681 TI - Synthetic dressings. PMID- 1737682 TI - Bacillary angiomatosis. PMID- 1737683 TI - Wounds that will not heal: the Buruli ulcer. PMID- 1737684 TI - Rational approach to wound care. PMID- 1737685 TI - Therapy of chronic idiopathic urticaria with nifedipine. PMID- 1737686 TI - "Two-step" pemphigus induction by ACE-inhibitors. AB - Pemphigus lesions appeared in a 58-year-old man who was taking captopril for his hypertension. Drug withdrawal resulted in complete remission of the eruption. The subsequent use of enalapril as an antihypertensive agent caused a recurrence of pemphigus lesions along with onset of itching and dermographism. Intercellular antibodies were not found. Discontinuance of enalapril therapy had no effect on the clinical course. Steroid treatment was needed to resolve the eruption. Recently repeated immunofluorescent studies disclosed intercellular IgG antibodies in the serum at a low titer. Pemphigus induction could be initially related to the thiol acantholytic property of captopril. Subsequent production of intercellular antibodies and drug-activation of the kinin system could be responsible for relapsing. PMID- 1737687 TI - Differentiation of bullous pemphigoid from epidermolysis bullosa acquisita on frozen skin biopsies. AB - Patients with bullous pemphigoid and epidermolysis bullosa acquisita may have similar clinical, histologic, and routine immunohistologic features. These two diseases can be distinguished by routine diagnostic studies either on a patient's serum tested by indirect immunofluorescence on salt-split normal skin or by obtaining a fresh perilesional skin biopsy, inducing a split at the lamina lucida, and testing for the site of IgG deposition by direct immunofluorescence. Often the serum studies are negative, while direct immunofluorescent studies yield the characteristic linear IgG staining of the basement membrane zone. To eliminate the need for a repeat biopsy to make a laboratory differential diagnosis, we studied the efficacy of salt-splitting perilesional skin biopsies that had been previously submitted and frozen for routine direct immunofluorescent studies. The biopsies were thawed, salt-split, and processed for direct immunofluorescence. Three epidermolysis bullosa acquisita biopsies and seven bullous pemphigoid biopsies examined demonstrated IgG staining at sites consistent with their respective diagnoses. The IgG appeared in the dermal side of the split biopsies in epidermolysis bullosa acquisita and predominantly, or exclusively, in the epidermal side in bullous pemphigoid. Thus the direct immunofluorescent study of previously frozen and subsequently salt-split skin biopsies may be used for the differential diagnosis of bullous pemphigoid from epidermolysis bullosa acquisita. In most cases, it may eliminate the need for a repeat biopsy. PMID- 1737688 TI - Bullous diseases in Malaysia: epidemiology and natural history. AB - The characteristics of three primary bullous diseases, pemphigus, pemphigoid, and dermatitis herpetiformis, seen in this country, probably reflecting this region, are discussed and compared to those reported in the literature in the West. One hundred and forty-eight patients with bullous diseases were seen over a period of 15 years. The criteria for confirmation of clinical diagnosis were the findings of the direct immunofluorescent test. Pemphigus vulgaris was the commonest bullous disease. The incidence of bullous pemphigoid was highest in the Indians of Malaysian origin, and they are also more likely to develop pemphigus vulgaris than any other ethnic group. Linear IgA type formed the entire group of dermatitis herpetiformis. The granular type was not seen at all. The patients were treated with prednisolone alone or together with methotrexate or azathioprine. Dapsone alone controlled the dermatitis herpetiformis. The known association between pemphigus and other diseases with immunologic disturbances was not found in this study. The natural history of the bullous disease as seen in the follow-up patients is described. Deaths in pemphigus and pemphigoid were more due to either complications of steroid therapy or unassociated diseases than the primary disease itself. Introduction of immunofluorescence as a diagnostic tool in pemphigus and extension of this facility to other bullous diseases has led to detailed characterization of these diseases as seen in the West; however, publications in English dealing with epidemiologic aspects of bullous diseases in this region are rare.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737689 TI - Pemphigus vulgaris following a cutaneous thermal burn. AB - Pemphigus vulgaris developed in a 59-year-old man following a cutaneous thermal burn. This is an example of induced pemphigus and should be included with the small number of cases where this sequence has been reported. PMID- 1737690 TI - Carotenoderma: a possible pit-fall in the immunopathologic diagnosis of pemphigus vulgaris. AB - A 30-year-old woman presented with an orange-yellow discoloration of the skin, most noticeable on the palms and soles and nasolabial folds; sclera appeared normal. The patient had observed the abnormal pigmentation of her skin 3 months earlier and noticed that it had become more evident after a sauna she had taken 2 days before our examination. In the last 3 years the patient's diet included about 2 kg of oranges daily (which are notoriously rich in carotene) following her own original idea. Complete laboratory analyses were normal. In particular, thyroid and liver function tests were in the normal range as were serum lipid levels. The serum carotene levels were 410 mg/dL (NV 20-150 mg/dL) and the levels of vitamin A 68 mg/dL (NV 25-60 mg/dL). A punch biopsy, taken from the palm of the right hand, observed under an optic microscope showed an autofluorescence in the superficial horny layer and a pemphigus-like pattern of intercellular autofluorescence. A month after the interruption of the orange-rich diet, the abnormal coloration of the skin disappeared and serum levels of carotene and vitamin A were normal. PMID- 1737691 TI - Porokeratosis of Mibelli following heart transplant. AB - A 59-year-old white man with a history of Sydenham's chorea received a mitral valve prosthesis in 1962. He sustained an anterolateral myocardial infarction in 1983. In 1984, he received a heart transplant. To prevent heart rejection, he was initially treated with cyclosporine 12 mg/kg/day and prednisone 90 mg b.i.d. In 1987, azathioprine 100 mg daily was added. In 1989, at the time of our evaluation, his medications included cyclosporine 80 mg b.i.d., prednisone 10 mg b.i.d., and azathioprine 75 mg/day. Since his heart transplant surgery he had not taken any thiazide medication. The patient noted a lesion on his right thigh; the lesion appeared in 1986, 2 years after his heart transplant. On examination in 1989, the lesion was a 2 cm wide annular plaque with a shiny atrophic center and raised border. Both the clinical appearance and pathology were consistent with a diagnosis of porokeratosis of Mibelli. No family history of porokeratosis was elicited. PMID- 1737692 TI - Granuloma annulare and disseminated herpes zoster. AB - A 71-year-old man was admitted to the Wake Forest University/Baptist Hospital Medical Center on February 1, 1989, with pharyngitis and a cutaneous eruption that began that day. The past history was significant for a diagnosis of chronic lymphocytic leukemia (CLL) made in 1984, and for longstanding hypertension, severe coronary artery disease, and prostatic hypertrophy. The patient had required no therapy for his CLL until August, 1988, when he developed hemolytic anemia and was treated with oral chlorambucil, 4 mg/day, and a tapering course of prednisone. By December, 1988, the prednisone therapy had been discontinued, but the patient required hospital admission for pneumococcal pneumonia, which responded well to intravenous antibiotic therapy. One day prior to the current admission the patient complained of persistent fevers, sore throat, productive cough, and headache. He noted a new cutaneous eruption on the day of admission in February, 1989. The past history was positive for occasional herpes stomatitis. The patient did not know if he had previously been infected with varicella. Skin examination revealed multiple (greater than 20), single, and grouped vesicles in a generalized distribution involving the bilateral trunk, head, neck, arms, and legs. The heaviest involvement was on the right posterior auricular area and on the neck. A Tzanck preparation obtained from an early lesion was positive for multinucleated giant cells. Viral culture was negative at 24 hours and at 1 week. A skin biopsy of an early vesicular lesion was performed and revealed intraepidermal vesicles with acantholysis and giant cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737693 TI - Keratitis, ichthyosis, and deafness (KID) syndrome: management with chronic oral ketoconazole therapy. AB - Extensive cutaneous mycoses have been described in patients with the keratitis, ichthyosis, and deafness (KID) syndrome. We present a case occurring in a 48-year old woman where improvement in the ichthyosiform dermatosis, stabilization of her ocular disease, and apparent partial prevention of further cutaneous malignancies occurred in association with ketoconazole therapy. PMID- 1737694 TI - Bulgarian dermatology. PMID- 1737695 TI - Inflammatory tinea capitis (kerion) mimicking dissecting cellulitis. PMID- 1737696 TI - Teaching and learning materials in leprosy (TALMILEP) (a joint project of ILEP- International Federation of Anti Leprosy Associations. PMID- 1737697 TI - Introduction of anthralin into dermatology. PMID- 1737698 TI - Can we diagnose a drug-induced pemphigus? PMID- 1737699 TI - Therapeutic use of "prizing" and its effect on self-concept of elderly clients in nursing homes and group homes. AB - The purpose of this study was to ascertain the effect of nurse high prizing and nurse low prizing during group therapy in changing the self-concept of institutionalized aged persons. The hypothesis tested was that institutionalized aged clients participating in group therapy who receive nurse high prizing will show an increase in self-concept as measured by the Tennessee Self-Concept Scale (TSCS) when compared with those aged clients in the same settings participating in group therapy who receive nurse low prizing or those aged clients constituting the matched control groups. The study used an existing data source generated from the research of Williams and Lindell to conduct a secondary analysis of a variable not previously investigated. Mean difference scores from the posttest total self-concept score and subscales of the TSCS were analyzed in conjunction with the levels of prizing within the experimental and control groups. Using the Scale for Rating Prizing, two nurse raters judged the degree of prizing on 40 randomly extracted video segments. The findings indicated that 47.1% of those subjects who received low prizing decreased in self-concept; 68.4% of those who received high prizing increased in self-concept. No change in self-concept was noted in the control group. Findings were significant at the .0001 level. Investigating the effect of nurse high and low levels of prizing on client self concept completes the Rogerian trilogy of therapist-offered conditions with this same sample of subjects. Extension of previous studies adds to the ever-growing body of nursing knowledge and increases the certitude, casualty, and generalizability of such investigations. PMID- 1737700 TI - Treating depression in well older adults: use of diaries in cognitive therapy. AB - A study was conducted with 103 community-based, low-income, well elderly persons who resided in high-rise apartments and were functionally independent. The nursing framework was Roy and Roberts' (1981) adaptation model and techniques from Beck's (1976) theory on cognitive therapy. This study had the dual purpose of determining nurses' ability to identify normal adaptive reactive depression and use techniques from cognitive therapy for depressed subjects. These nurses were able to identify depression using the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) guidelines with 92% accuracy. Participants were divided into three groups: control group, crafts group, and experimental group. Over 8 weeks, the experimental group received nursing intervention aimed at reinforcing positive input thought patterns. Daily diaries were used for discussion. The experimental group demonstrated a significant reduction in depressive symptoms. The group receiving craft classes decreased their depression scores, suggesting attention-effects depression. The control group demonstrated no significant change in depression scores. PMID- 1737701 TI - Ethical issues in restructuring of psychiatric services. AB - The restructuring of health care services is occurring at an increasing rate. Among those most common are the types known as vertical integration, illustrated by the development of psychiatric services within acute care settings. These restructured psychiatric services have implications for psychiatric care and nursing. In some instances, they raise ethical issues. The purpose of this article is to explore ethical issues in restructuring of psychiatric services and to offer suggestions for retaining quality nursing care. PMID- 1737702 TI - Psychiatric-mental health nursing: career characteristics, professional activities, and client attributes of members of the American Nurses Association Council of Psychiatric Nurses. AB - As the twenty-first century approaches, psychiatric nursing is reviewing its past and speculating about its future. This article reports on the current status of 525 psychiatric-mental health nurses. The nurses responded to a questionnaire designed to elicit information on career characteristics, professional activities, and client attributes. The nurses work primarily in acute care institutions or hospitals. The typical client is white, middle class, and adult. The focus of care in mental health is moving to the community. If psychiatric nurses want a viable role in the mental health system of the future, they must begin to develop a system of care for at-risk populations in the community now. PMID- 1737703 TI - Milieu therapy: a review of development of this concept and its implications for psychiatric nursing. AB - Milieu therapy has long existed as an effective treatment modality for the mentally ill. It has also been a significant aspect of psychiatric-mental health nursing practice for several decades. This article reviews the history of milieu therapy and the role that psychiatric-mental health nursing staffs have in its implementation. The authors suggest strategies for milieu management and future implications for milieu therapy. PMID- 1737704 TI - Nursing program to meet the challenge of caring for patients with water intoxication. AB - This article describes a program that is effective in working with psychiatric patients who have trouble with excessive water intake. The purpose of the program is to provide consistent treatment in a controlled and therapeutic environment in which the special needs of these patients can be met. We incorporate a variety of nursing interventions suggested by the literature to help meet the goals of the program. As a result of the program, disruptive behavior has decreased and patients have learned skills to help them manage their illness. An additional benefit of the program is that working with water intoxication patients is no longer stressful for staff. PMID- 1737705 TI - Supply and demand factors in the determination of Medicare expenditures. AB - This article presents multivariate estimates of the effects of supply-side factors (e.g., provider reimbursement) and demand-side factors (e.g., beneficiary ability to pay) on state-level expenditures per enrollee in Medicare Part A and Part B. The results indicate that a 1 percent increase in elderly income significantly increases the propensity to use Medicare Part B services, resulting in a 0.45 percent increase in Part B expenditures per enrollee. By contrast, patients' ability to pay has a much weaker effect on Part A expenditures. Changes in provider reimbursement also exert a substantial effect on expenditures. A 1 percent rise in the Medicare Prevailing Charge Index raises Medicare Part B expenditures by 0.43 percent. Collectively, the findings of this study suggest that both limits on Medicare reimbursement to providers and increased beneficiary liability have substantial effects on Medicare costs. Whatever the merits of arguments for or against such controls, the responsiveness of Medicare expenditures to equal percentage changes in supply and demand factors appears to be of a similar order of magnitude. PMID- 1737706 TI - Medicare use in the last ninety days of life. AB - The introduction of Medicare's prospective payment system (PPS) has led to changes in the way hospitals are being used. This article examines concomitant changes in the use of Medicare-covered services during the last 90 days of life, using data on more than 34,000 Medicare beneficiaries who died during the years 1982-1986. We focus on questions pertaining to changes in practice patterns that include location of death, hospital utilization, use of other covered services, and spending. We find that use of hospitals and other health services by Medicare beneficiaries during the last 90 days of life changed markedly over this period, which included the introduction of PPS in late 1983. The percentage of deaths occurring in hospitals decreased sharply from 1982 to 1986, especially in PPS states relative to waivered states; this effect seems primarily due to reductions in length of stay rather than reduced admission rates, which did not change significantly. Use of home care, durable medical equipment (DME), and physicians' office services also increased sharply during the last 90 days of life, but with no consistent evidence that the introduction of PPS was associated with these changes or with the level or mix of Medicare expenditures for these patients. Medicare spending in this period of life rose at the same rate as medical care price inflation, and about 75 percent of reimbursements continued to be hospital payments, despite the utilization changes. PMID- 1737707 TI - Predicting length of stay for patients with psychoses. AB - The Computerized Psychiatric Severity Index (CPSI) and 22 patient variables were used to predict length of hospitalization for 304 psychiatric patients in DRG 430 who were diagnosed with schizophrenia or affective disorder and had no secondary diagnoses. Length of stay, which correlated .96 with total charges, was used as the dependent variable (measure of resource use). The patient variables and CPSI score explained 32.5 percent of the variation in length of stay for all of DRG 430 (27.5 percent for affective disorder patients and 70.3 percent for schizophrenia patients). Addition of the treatment variable "receipt of ECT" (electroconvulsive therapy) permitted the regression models to explain 40.9 percent of the variation in length of stay (36.24 percent for affective disorder and 71.22 percent for schizophrenia). In each regression model, maximum CPSI score was significant, indicating that much heterogeneity in DRG 430 can be explained by CPSI. Using one payment for such a diverse group places health care institutions at great risk of financial loss. Our study indicates that a continuing need exists for research in the area of case-mix measures for psychiatric inpatients. PMID- 1737708 TI - Adapting the SERVQUAL scale to hospital services: an empirical investigation. AB - Defining and measuring the quality of service has been a major challenge for health care marketers. A comprehensive service quality measurement scale (SERVQUAL) is empirically evaluated for its potential usefulness in a hospital service environment. Active participation by hospital management helped to address practical and user-related aspects of the assessment. The completed expectations and perceptions scales met various criteria for reliability and validity. Suggestions are provided for the managerial use of the scale, and a number of future research issues are identified. PMID- 1737709 TI - An operational definition of the homebound. AB - Homebound status is a critical eligibility criterion for Medicare reimbursement of some home care services, yet little discussion has been undertaken to establish a valid definition of it. We propose an operational definition of homebound status, and we measure its validity for community-dwelling elderly in the Massachusetts Health Care Panel Study (MHCPS). The MHCPS is a longitudinal study of a cohort of elderly persons (N = 1,625), which began in 1974, with follow-up surveys in 1976, 1980, and 1985. Validity was measured by comparing responses from the operational measure to persons' responses to questions that we judged should be associated with a valid measure of homebound status. This construct validity method resulted in correlations that were significant and in the expected direction, and that suggested that this operational measure is a highly specific, moderately sensitive, valid measure. These results underscore the need for researchers investigating the homebound to discuss the validity and limitations of their homebound measures, and in what context these measures are useful. PMID- 1737710 TI - A randomized trial of the cost effectiveness of VA hospital-based home care for the terminally ill. AB - All admissions to a 1,100-bed Department of Veterans Affairs (VA) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then randomly assigned to VA hospital-based team home care (HBHC, N = 85) or customary care (N = 86). Patient functioning, and patient and caregiver morale and satisfaction with care were measured at baseline, one month, and six months. Health services utilization was monitored over the six-month study period and converted to cost. Findings included no differences in patient survival, activities of daily living (ADL), cognitive functioning, or morale, but a significant increase in patient (p = .02) and caregiver (p = .005) satisfaction with care at one month. A substitution effect of HBHC was seen. Those in the experimental group used 5.9 fewer VA hospital days (p = .03), resulting in a $1,639 or 47 percent per capita saving in VA hospital costs (p = .02). As a result, total per capita health care costs, including HBHC, were $769 or 18 percent (n.s.) lower in the HBHC sample, indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost. PMID- 1737711 TI - Laser ignition of surgical drapes. PMID- 1737712 TI - Do pledgets protect the tracheal tube cuff from lasers? PMID- 1737713 TI - Laser contact tips and tracheal tubes. PMID- 1737714 TI - Understanding the fire hazard. PMID- 1737716 TI - Stockert/Shiley CAPS multiflow roller pump stoppages. PMID- 1737715 TI - Preventing, preparing for, and managing surgical fires. PMID- 1737717 TI - Circulating-fluid pumps: do not use for ECMO. PMID- 1737718 TI - Laser-resistant tracheal tubes. PMID- 1737719 TI - Antibacterial therapy of community-acquired chest infections. PMID- 1737720 TI - Uptake of minocycline by Escherichia coli. AB - Uptake of tetracyclines into Escherichia coli was assessed with a strain carrying a tetA-lacZ translational fusion, in which expression of the enzyme is controlled by the pSC101 tetR repressor gene, by examining beta-galactosidase induction. The ability of tetracycline analogues to induce beta-galactosidase synthesis was correlated with their hydrophobicity, such that hydrophobic analogues were poor enzyme inducers. Treatment of E. coli with polymyxin B nonapeptide (PMBN) rendered cells more permeable to minocycline, but not to tetracycline. PMID- 1737721 TI - Antibiotic resistance and plasmids in Staphylococcus aureus from normal populations. AB - Antibiotic resistance, plasmid profiles and plasmid structures were examined in nasal Staphylococcus aureus collected from a random sample of normal individuals in the mid 1960s and from women at an antenatal clinic in 1989. The results were generally similar except for an increase in the resistance to penicillin in the later sample. The plasmid population had changed little though more uncategorized plasmids were evident in the 1960s samples. PMID- 1737722 TI - The treatment of non-typhi salmonellosis. PMID- 1737723 TI - Comparative in-vitro activity of new quinolones against clinical isolates and resistant mutants. AB - The in-vitro activity of five new fluoroquinolones, WIN 57273, sparfloxacin, fleroxacin, temafloxacin and ciprofloxacin was determined against 543 recent clinical isolates and eight quinolone resistant strains derived by mutation and their five parent strains. WIN 57273 was the most active compound against Gram positive bacteria, sparfloxacin had a broad spectrum which was similar to that of ciprofloxacin. Ciprofloxacin showed the greatest activity against Gram-negative bacteria. Temafloxacin showing some activity against Gram-positive organisms and Acinetobacter spp. Fleroxacin was the least active compound studied. Compared to wild type parent strains, the mutated strains produced the following results. In Enterobacter cloacae OmpF deficiency increased the MICs of all quinolones by 8-32 fold. In Pseudomonas aeruginosa OmpF deficiency had a limited effect, Omp D2 deficiency combined with an increased lipopolysaccharide content produced greater resistance, i.e. 4-16-fold; mutations in gyrase were associated with variously increased MICs, depending on the strain and compound tested. PMID- 1737724 TI - In-vitro activity of imipenem, in comparison with cefuroxime and ciprofloxacin, against coagulase-negative staphylococci in broth and peritoneal dialysis fluid. AB - The activity of cefuroxime, ciprofloxacin and imipenem against 50 coagulase negative staphylococci (CNS) strains isolated from patients with peritonitis while on continuous ambulatory peritoneal dialysis (CAPD) was examined. Strains were cultured in both used peritoneal dialysis fluid (PUD) and broth (ISB) in an atmosphere of air with 5% CO2. MICs of cefuroxime, ciprofloxacin and imipenem differed significantly between the two media for 40%, 26% and 42% of strains, respectively. In three-quarters of these cases the MICs were higher in PUD compared to ISB. The ability of each antibiotic to kill six strains of CNS adherent to silicone rubber was also examined. Once again, differences in killing were noted between the two media. At least two-thirds of the strains remained viable in the presence of concentrations of antibiotic equal to the MBC of each antibiotic and at least one-third survived antibiotic concentrations equivalent to those attained during treatment. Assessment of activity in PUD may provide a more realistic test for antibiotics to be used in the treatment of CAPD peritonitis. PMID- 1737725 TI - Multicentre study on antibiotic susceptibilities of anaerobic bacteria to cefoperazone-sulbactam and other antimicrobial agents. AB - The antibiotic susceptibilities of 241 anaerobic bacteria recovered from six geographic sites in North America were tested by agar dilution to cefoperazone sulbactam and other drugs. Of the 189 Bacteroides fragilis group isolates, only one was resistant to cefoperazone-sulbactam (0.5%) or ampicillin-sulbactam (0.5%), and none was resistant to ticarcillin-clavulanate or chloramphenicol. No resistance to cefoperazone-sulbactam was observed among the other Bacteroides spp., Clostridium spp., or Peptostreptococcus spp. Resistance to cefoperazone sulbactam is not commonly observed against anaerobic bacteria recovered from different geographical sites across North America. PMID- 1737726 TI - In-vivo and in-vitro studies on the effect of amphotericin B on endothelin release. AB - Since amphotericin B nephrotoxicity is mediated, in part by hypoxic tubular injury, the role of endothelin in the renal vasoconstriction, characteristic of amphotericin toxicity has been studied. Intact and salt depleted rats were infused with amphotericin B (20 micrograms/kg per min) or 5% dextrose over 20 min. Plasma endothelin levels determined at the conclusion of the infusion period, did not differ between the experimental groups, despite a marked reduction in renal blood flow noted in rats infused with amphotericin B. Amphotericin B (10(-5)-10(-7) M) did not stimulate endothelin release from cultured bovine aortic endothelial cells. However, in a model of chronic amphotericin nephrotoxicity produced by repeated daily intraperitoneal injections of amphotericin B (5 mg/kg) to salt depleted rats, renal failure was associated with elevated plasma endothelin levels (29.3 +/- 4.4 fmol/mL, vs 10.8 +/- 1.2 fmol/mL in salt depleted controls, P less than 0.01). We conclude that while plasma endothelin may be increased in chronic amphotericin B nephropathy, this peptide does not mediate the acute renal vasoconstriction associated with the infusion of this drug. PMID- 1737727 TI - Enterococcus faecium strains susceptible to ampicillin. PMID- 1737728 TI - Detection of methicillin resistance in Staphylococcus aureus and coagulase negative staphylococci with the semi-automated API (ATB-plus) system. PMID- 1737729 TI - Susceptibility testing of cefpirome. PMID- 1737730 TI - Effect of cilastatin on the urinary metabolism of FCE 22101 in the rat. PMID- 1737731 TI - Pefloxacin penetration of renal parenchyma. PMID- 1737732 TI - Failure of oral ciprofloxacin in suppressing Staphylococcus aureus carriage in haemodialysis patients. PMID- 1737733 TI - Simultaneous major depression and panic disorder: treatment with electroconvulsive therapy. AB - BACKGROUND: Major depression and panic disorder commonly occur together. Patients with simultaneous depression and panic disorder may have a higher lifetime rate of suicide attempts and an overall worse prognosis than patients with either depression or panic disorder alone. In addition, preliminary work suggests that some of these patients may not respond satisfactorily to antidepressants. In this report, we describe the clinical courses of eight consecutive patients with simultaneous major depression and panic disorder who were referred for ECT at our institution. METHOD: Eight consecutive patients who met DSM-III-R criteria for simultaneous major depression and panic disorder received ECT. All eight patients were evaluated by a structured clinical interview and the patients' major depression and panic disorder were evaluated with a 7-point Clinical Global Impressions severity rating scale. RESULTS: Before ECT was begun, each subject's panic disorder and depression were rated as at least markedly ill. After receiving ECT, all eight showed improvement in their depression. In addition, none of the eight patients reported having a panic attack from the time of their fourth ECT treatment until discharge. CONCLUSION: In this report, eight consecutive patients with simultaneous major depression and panic disorder improved with ECT. Further work is required which examines the potential utility of ECT in treating these patients. PMID- 1737734 TI - T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. AB - BACKGROUND: Clinicians may not consider using the thyroid hormone liothyronine sodium (levorotary isomer of triiodothyronine [T3]) for augmentation of antidepressant drugs in depressed patients who are also receiving the precursor hormone levothyroxine (levorotary isomer of thyroxine [T4]) for thyroid disease. We now report on the successful use of T3 augmentation therapy in seven of nine depressed patients who were also receiving T4 for thyroid disease. METHOD: Following an earlier single case report, we prescribed T3 augmentation therapy for eight depressed patients who had not responded to an adequate antidepressant drug trial and who were receiving T4 therapy for thyroid disease. T3 was prescribed in open-label fashion, and response was judged by the clinician, whose assessment was supplemented by the use of standardized rating scales. RESULTS: Seven of the nine patients were judged to respond to T3 augmentation. CONCLUSION: These results are consistent with a report of differential effects for T3 versus T4 augmentation in depressed patients free of thyroid disease. The results have implications for the treatment of depression in the presence of thyroid disease and for the mechanism of thyroid hormone potentiation of antidepressants. PMID- 1737735 TI - The use of low-dose intranasal midazolam to treat panic disorder: a pilot study. AB - BACKGROUND: Drug therapy of panic disorder, despite the intermittent nature of the panic attack, requires daily administration of antidepressants, which are often not tolerated, or benzodiazepines, which can result in physical dependence and withdrawal. The use of rapidly acting, low-dose intranasal midazolam to prevent incipient panic suggested itself to us as a novel alternative treatment strategy. METHOD: We conducted a 6-week double-blind, placebo-controlled, crossover-design pilot study of the safety and efficacy of p.r.n. low-dose intranasal midazolam in five patients diagnosed with DSM-III-R panic disorder. RESULTS: One to two drops of midazolam (approximately 0.25 to 0.5 mg) was well tolerated and highly effective in preventing incipient panic attacks and in reducing the overall weekly frequency of attacks. CONCLUSION: Intermittent intranasal midazolam shows promise as a novel alternative treatment for panic, but a controlled study of its efficacy and safety (including abuse potential) must be conducted. PMID- 1737736 TI - An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder. AB - BACKGROUND: We investigated whether patients with DSM-III-R panic disorder and patients with social phobia could be distinguished on the basis of selected demographic variables and by several commonly used anxiety and phobia rating scales. METHOD: Sixty-six patients with social phobia and 60 patients with panic disorder (42 with and 18 without agoraphobia) were studied. Subjects completed a battery of self-report measures that assessed phobic fears, avoidance, and related problems. RESULTS: Social phobic patients showed an earlier age at onset than the panic disorder group, and there was a trend for more social phobics to have never married. Social phobics reported significantly greater levels of social phobic avoidance and distress, fear of negative evaluation, and avoidance of social situations than the panic disorder patients who reported more overall anxiety and rated themselves as significantly more avoidant of situations involving exposure to public places and to blood or injury. Discriminant function analyses showed that social phobic and panic disorder patients can be reliably discriminated on these scales. CONCLUSION: The results of this study lend further support for the validity of the DSM-III-R nosologic distinctions between social phobia and panic disorder. Furthermore, generalized social phobia appears to be remarkably different from discrete social phobia on these measures. This study provides less support for considering panic disorder with agoraphobia to be distinct from panic disorder without agoraphobia. PMID- 1737737 TI - Symptom relapse in bulimia nervosa and obsessive compulsive disorder after treatment with serotonin antagonists. PMID- 1737738 TI - Fluoxetine-lithium treatment for kleptomania. PMID- 1737739 TI - Bipolar disorder and Crohn's disease. PMID- 1737740 TI - The intermetamorphosis syndrome. PMID- 1737741 TI - Treatment of imipramine-resistant recurrent depression, III: Efficacy of monoamine oxidase inhibitors. AB - BACKGROUND: The effectiveness of monoamine oxidase inhibitors (MAOIs) in tricyclic resistant depression has received surprisingly little systematic study. METHOD: Patients who failed to respond to sustained, adequate treatment with the tricyclic imipramine (mean maximum dosage = 260 mg/day) and interpersonal psychotherapy were withdrawn from imipramine and treated in a standardized, but open-label 6-week trial with either phenelzine (N = 4; 60 mg/day) or tranylcypromine (N = 36; mean = 38.5 mg/day) and continued interpersonal psychotherapy. RESULTS: Forty of 42 patients (95%) completed the trial, of whom 23 (58%) responded to treatment. Highly significant improvement was documented on measures of depression, reversed neurovegetative symptoms, and somatic symptoms. Response was significantly correlated with severity of depression (pre-MAOI score on the Hamilton Rating Scale for Depression), severity of a composite score of anergic and reversed neurovegetative features, and low levels of improvement during initial imipramine/interpersonal psychotherapy. Of patients who met criteria for proposed subforms of anergic or atypical depression, 67% (18/27) responded (p less than .05); 77% (17/22) of patients who scored above the mean on the composite measure of anergic and reversed neurovegetative features responded (p less than .01). CONCLUSION: These findings provide strong evidence of the utility of MAOIs in tricyclic-resistant depression, especially in patients with features such as fatigue, volitional inhibition, motoric retardation, hypersomnia, and/or weight gain. PMID- 1737742 TI - The P2 element of the td intron is dispensable despite its normal role in splicing. AB - The P2 region of group I introns has been proposed to be involved in the correct positioning of the P1 5'-splice site duplex in the catalytic core (Michel, F., and Westhof, E. (1990) J. Mol. Biol. 216, 585-610). The behavior of delta P2 deletion mutants of the td intron is consistent with this hypothesis. The delta P2 mutants are capable of site-specific hydrolysis, indicating that the conformation of the ribozyme is not grossly altered, but they are incapable of transesterification reactions at the splice sites, as would be predicted if P1 is not appropriately aligned within the catalytic core. Nevertheless, the function of the P2 element can be bypassed in specific pseudorevertants isolated by genetic selection from the delta P2 mutants. These results, together with phylogenetic data, support the existence of alternate strategies to create a functional P1-core interaction. PMID- 1737743 TI - Oxidation-reduction-sensitive binding of lung protein to rat catalase mRNA. AB - Air-breathing organisms experience an elevated concentration of oxygen mainly under two conditions. One occurs at birth when the O2 tension in the lung increases from approximately 25 torr present in utero to approximately 100 torr. The lungs, in particular, are also exposed to hyperoxia when oxygen is administered for therapeutic reasons. Under hyperoxic conditions, increased lung antioxidant enzyme activity is important for survival. The molecular basis for the increase in antioxidant enzyme gene expression under these circumstances is not well understood; in hyperoxia-exposed neonatal rats the elevation of lung catalase activity is not due to an increased rate of transcription but is associated with an increased concentration of catalase mRNA due to enhanced stability of the mRNA (Clerch, L.B., Iqbal, J., and Massaro, D. (1991) Am. J. Physiol. 260, L428-L433). We now show that neonatal rat lung protein forms specific complexes with catalase mRNA; this binding is redox-sensitive since when oxidizing agents are added binding is abolished but is restored by reducing agents. Our data also indicate lungs from hyperoxia-exposed rats have a larger proportion of catalase RNA-binding protein in oxidized form than lungs from air breathing rats. This redox-sensitive binding of protein to catalase mRNA may be important in the control of catalase gene expression. PMID- 1737744 TI - Inactivation of endothelin I by deamidase (lysosomal protective protein). AB - Deamidase cleaves ester and peptide bonds in various substrates and deamidates protected COOH-terminal amino acids. It preferentially hydrolyzes peptides which contain hydrophobic amino acids in the P1' and/or P1 position. Because the COOH terminal end of endothelin I contains the hydrophobic sequence -Ile19-Ile20-Trp21 OH, we investigated whether human deamidase, purified from platelets, could inactivate this peptide. We found that deamidase readily cleaved off Trp21 with an acid pH optimum, a Km = 22 microM, a kcat of 1454 min-1, and a kcat/Km of 68 microM-1 min-1. We also found the enzyme to be present in target cells of endothelin, in vascular smooth muscle cells. Extracts of cultured vascular smooth muscle cells cleave both the synthetic fluorescent substrate 5 dimethylaminonaphthalene-1-sulfonyl(Dns)-Phe-Leu-Arg and endothelin I by releasing the COOH-terminal amino acid. The reaction was inhibited by diisopropyl fluorophosphate, benzyloxycarbonyl-Gly-Leu-Phe-CH2Cl, and p chloromercuribenzenesulfonate, which inhibit the purified deamidase, but not by inhibitors of some other peptidases. The rate of hydrolysis of endothelin I in the soluble, 100,000 x g final supernatant of the homogenized smooth muscle cells was 2.1 mumol/h/mg and 3.1 mumol/h/mg for Dns-Phe-Leu-Arg. Thus, smooth muscles, platelets, and many other tissues which contain the deamidase can inactivate endothelin by cleaving the COOH-terminal tryptophan. PMID- 1737745 TI - Recognition of substrates by tyrosylprotein sulfotransferase. Determination of affinity by acidic amino acids near the target sites. AB - The sulfation of proteins by tyrosylprotein sulfotransferase (TPST) is highly site-specific. In this study, we examined the sequence specificity of the target site for TPST by determining the kinetics of rat liver TPST with peptides related to the sequence of the C4 component of complement. The data obtained from this study demonstrate that selective elimination of negative charges from the -5 to +5 region of the acceptor tyrosine, either by removal or by isosteric substitution or the acidic amino acids in the region, produced a substantial change in the Km value, with relatively little effect on Vmax. Substitutions at 1 and +1 positions increase the Km value by 22- and 4-fold, respectively, whereas removal of the acidic amino acids from the -5, -4, or +4 positions increased the Km values by a factor of 2-4. The effect of elimination of an acidic amino acid on the Km value was constant and specific for its particular position in relation to tyrosine, and the effect of modification of more than one amino acid was multiplicative. This study provides evidence that: 1) acidic residues near tyrosines promote sulfation by increasing the affinity of enzyme-substrate binding and have little effect on catalytic rate; 2) the contribution of each acidic residue to affinity for TPST is independent and varies according to position relative to the acceptor tyrosine; and 3) the enzyme interacts with a segment of at least 4-5 residues on each side of the tyrosine, with the residues on the -1 and +1 positions being the most important determinants. In general, residues on the NH2-terminal side of the tyrosine have a greater effect on affinity for TPST. PMID- 1737746 TI - Cloning of TFC1, the Saccharomyces cerevisiae gene encoding the 95-kDa subunit of transcription factor TFIIIC. AB - The yeast gene encoding the 95-kDa subunit of the class III gene transcription factor TFIIIC was cloned. This gene, termed TFC1 (transcription factor C, gene 1), was isolated by screening a lambda gt11 yeast cDNA expression library using a polyclonal antiserum preparation which was previously shown to specifically recognize the 95-kDa subunit of yeast TFIIIC (Parsons, M. C., and Weil, P. A. (1990) J. Biol. Chem. 265, 5095-5103). TFC1 was found to be a single copy gene which contained a continuous open reading frame about 2 kilobases in length. TFC1 was shown to encode the 95-kDa subunit of TFIIIC by several criteria. Like the authentic yeast protein, the protein encoded by TFC1 had an apparent molecular weight of 95,000. In addition, the protein encoded by the TFC1 gene bound to the same antibody species as the yeast 95-kDa subunit of TFIIIC. Last, the sizes of the cleavage products of the Escherichia coli-expressed protein were indistinguishable from those of the cleavage products of the bona fide yeast 95 kDa protein. PMID- 1737747 TI - Identification of chromophore binding domains of yeast DNA photolyase. AB - Photolyases contain two chromophores, flavin plus either methenyltetrahydrofolate (MTHF) or 8-OH-5-deazaflavin (HDF). Amino acid sequence comparison reveals that all photolyases sequenced to date have extensive sequence homology in the carboxyl-terminal half; in the amino-terminal region the folate and deazaflavin class enzymes are more homologous to other members of the same class. This modular arrangement of sequence homologies suggests that the amino-terminal half of photolyase is involved in MTHF or HDF binding whereas the carboxyl-terminal half carries the flavin binding site. In this study we attempted to identify such structural domains of yeast photolyase by partial proteolysis and gene fusion techniques. Partial digestion with chymotrypsin yielded an amino-terminal 34-kDa fragment containing tightly bound MTHF and a carboxyl-terminal 20-kDa polypeptide which lacked chromophore or DNA binding activity. However, a fusion protein carrying the carboxyl-terminal 275 amino acids of yeast photolyase bound specifically to FAD but not to MTHF or DNA. We conclude that the amino-terminal half of yeast photolyase constitutes the folate binding domain and that the carboxyl-terminal half carries the flavin binding site. PMID- 1737748 TI - Molecular cloning and characterization of grancalcin, a novel EF-hand calcium binding protein abundant in neutrophils and monocytes. AB - A novel EF-hand Ca(2+)-binding protein we have called grancalcin has been identified and characterized. This protein is particularly abundant in neutrophils and monocytes, with relatively small amounts in lymphocytes. The cDNA for this protein has been cloned and sequenced. The sequence predicts that the protein is composed of 217 amino acids, with a molecular mass of 24,010 daltons. It contains four EF-hand calcium-binding motifs and exhibits strong homology to sorcin, one of two proteins overexpressed in multidrug-resistant cells whose function is unknown. There are potentially one phosphorylation and two glycosylation sites. The 1.65-kilobase mRNA is detected in bone marrow and is present in neutrophils, monocytes, macrophages, B and T lymphocytes, and the promyelocytic cell line HL60s. The protein displays a Ca(2+)-dependent translocation to the granules and plasma membrane of neutrophils, suggesting that it might play an effector role in the specialized functions of these cells. PMID- 1737749 TI - Modulation of the mitochondrial permeability transition pore. Effect of protons and divalent cations. AB - We have studied the induction of the mitochondrial cyclosporin A-sensitive permeability transition pore (PTP) by the bifunctional SH group reagent phenylarsine oxide (PhAsO). Addition of nanomolar concentrations of the electroneutral H(+)-K+ ionophore nigericin to nonrespiring mitochondria in sucrose medium determines a dramatic increase of the time required for PTP induction by PhAsO, while no effect of nigericin is apparent in KCl medium. Using mitochondria loaded with the internal pH indicator 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein, we show that the effect of nigericin is mediated by the ionophore-induced acidification of matrix pH. Indeed, experimental manipulation of pHi by a number of treatments indicates that PTP induction is directly related to matrix pH, in that the PTP induction process becomes slower as pHi decreases at constant pHo. PTP induction by PhAsO in respiration-inhibited mitochondria is stimulated by Ca2+ and inhibited by a series of divalent cations. Since PhAsO induces the PTP even in the presence of excess EGTA and in the absence of respiration (Lenartowicz, E., Bernardi, P., and Azzone, G.F. (1991) J. Bioenerg. Biomembr. 23, 679-688), we have been able to study the Ca2+ dependence of the induction process. We show that the apparent Km for Ca2+ activation is about 10( 5) M and that Ca2+, cyclosporin A, and inhibitory Me2+ ions behave as if they were competing for the same binding site(s) on the pore. Since similar results are obtained from patch-clamp experiments on the mitochondrial megachannel (Szabo, I., Bernardi, P., and Zoratti, M. (1992) J. Biol. Chem. 267, 2940-2946), we suggest that (i) the PTP and the mitochondrial megachannel are the same molecular structures and (ii) the same factors affect both the process of pore induction and its open-closed orientation. PMID- 1737750 TI - Derivation of the amino acid sequence of rat C-reactive protein from cDNA cloning with additional studies on the nature of its dimeric component. AB - Rat C-reactive protein (CRP) is unique among mammalian CRPs in being a glycoprotein and in containing a covalently linked dimer in its pentameric structure. To investigate these features, cDNA clones encoding rat CRP were isolated from an expression library, and the primary structure of the protein was derived. Taken along with the results of Northern blotting, we conclude that a single mRNA of approximately 2,500 nucleotides codes for a precursor of rat CRP with a signal sequence of 19 amino acids and a polypeptide of 211 amino acids, the latter sharing extensive homology with human, rabbit, and mouse CRPs. The deduced sequence agreed with results obtained from partial microsequencing and mapping by fast atom bombardment-mass spectrometry. Two potential sites for N glycosylation (Asn-128 and Asn-147) and a C-terminal heptapeptide (Leu-205 to Ser 211, containing two cysteines at positions 208 and 209) were unique to rat CRP. The protein was also shown to be composed of five apparently identical monomers, two of which form a dimer linked by two interchain disulfide bonds involving Cys 208 and Cys-209. These same cysteines form an intrachain disulfide bond in the other three monomers. The primary structure of rat CRP and the basis of dimer formation have, therefore, been elucidated. PMID- 1737751 TI - The glycine-rich domain of nucleolin has an unusual supersecondary structure responsible for its RNA-helix-destabilizing properties. AB - Nucleolin, a major nucleolar protein implicated in preribosome assembly and transcriptional regulation, possesses a C-terminal domain unusually rich in glycine, arginine, and phenylalanine residues. A polypeptide (p10), corresponding to this domain, has been synthesized by means of an Escherichia coli expression system and purified to homogeneity. Nitrocellulose binding assays have clearly shown that this domain of nucleolin is capable of interacting with RNA, and indeed all nucleic acids tested, in an efficient but nonspecific manner. A combination of circular dichroism and infrared spectroscopy provide strong evidence that repeated beta-turns are a major structural component of this polypeptide, which is entirely consistent with its amino acid composition and above all the presence of repeat motifs such as RGGF. Circular dichroism technique also shows that the interaction of p10 with RNA involves an unstacking of the nucleotide bases and an unfolding of the RNA secondary structure. While the role of the C-terminal domain of nucleolin in vivo has yet to be established, our findings suggest that it may act to unfold regions of ribosomal RNA so that a second domain of nucleolin has access to its specific binding site. PMID- 1737752 TI - Low structural specificity for nucleoside triphosphates as antagonists of ADP induced platelet activation. AB - Although the platelet ADP receptor is thought to exhibit a high degree of structural selectivity, adenosine 5'-O-(thiotriphosphate) (ATP alpha S) is a potent inhibitor of ADP-induced platelet activation and has been recently shown to bind with high affinity (Kd 3 +/- 0.1 nM) to formaldehyde-fixed platelets and to be photoincorporated into an 18-kDa fragment beginning at Tyr-198 of glycoprotein (GP) IIb alpha (Greco, N. J., Yamamoto, N., Jackson, B. W., Tandon, N. N., Moos, M., Jr., and Jamieson, G. A. (1991) J. Biol. Chem. 266, 13627 13633). Further studies have now shown that guanosine 5'-O-(thiotriphosphate) (GTP alpha S) also binds to high affinity sites (Kd 4.7 +/- 0.9 nM; 13,600 +/- 1,140 sites/platelet) and to low affinity sites (Kd 470 +/- 85 nM; 135,900 +/- 19,400 sites/platelet). Competition binding studies showed that all GTP alpha S binding sites were accessible to ADP and vice versa. The corresponding pyrimidine nucleotide cytidine 5'-O-(thiotriphosphate) (CTP alpha S) was found to be similarly effective in competing in the binding of ADP and both 5'-O (thiotriphosphates) as well as uridine 5'-O-(thiotriphosphate) (UTP alpha S) were potent inhibitors of platelet shape change and aggregation. Ultraviolet irradiation of platelets in the presence of either [35S]GTP alpha S or [35S]UTP alpha S resulted in their specific incorporation into the alpha chain of GPIIb as previously shown with [35S]ATP alpha S. These results show that the structure of the nucleotide base has little influence on its ability to occupy the ADP-binding site on platelets, to function as an inhibitor of ADP-induced activation or to be photoincorporated into GPIIb alpha. PMID- 1737753 TI - The complete cDNA sequence of bovine coagulation factor V. AB - Lack of availability of a primary structure for bovine factor V has hindered detailed analysis of a vast majority of structure-function correlations on this molecule. To determine the primary structure of bovine factor V, we used liver mRNA as a template for the synthesis of three cDNA libraries. The sequences of seven overlapping cDNA clones infer two bovine factor V variants. Variant 1 results in a 6910-basepair (bp) cDNA including 103 bp of 5'-untranslated sequence, 6633 bp of coding sequence and 171 bp of 3'-untranslated sequence with a putative polyadenylation site. Variant 2 differs only in the size of the coding sequence (6618 bp). The open reading frame translates to factor V consisting of 2211 (or 2206) amino acids including a 28-amino acid signal peptide. Comparison of the amino acid sequences with human factor Va reveals 84% identity for the heavy and 86% for the light chains. In contrast, the B domain (connecting region) exhibits only 59% identity relative to the human molecule. The bovine B domain contains two repeats of a 14-amino acid structure that is contained only once in the human sequence. Bovine factor V lacks one of the nine amino acid repeats and one of the 17 amino acid repeats present in the human B domain. Factor V has little homology to the factor VIII molecule in the B domain. The 17-amino acid repeat missing in bovine factor V allows identification of an 18-amino acid sequence that is homologous to the B domain of human factor VIII. These 18 amino acids may either constitute the unique vestige of a divergent evolution between the B domains of factors V and VIII or reveal the convergent evolution toward a critical epitope involved in the activation of both procofactors. PMID- 1737754 TI - Expression, regulation, and tissue distribution of the Ch21 protein during chicken embryogenesis. AB - The Ch21 protein is one of the marker proteins whose synthesis and secretion by differentiating tibia chondrocytes is progressively increased during chicken embryogenesis (Descalzi-Cancedda, F., Manduca, P., Tacchetti, C., Fossa, P., Quarto, R. and Cancedda, R. (1988) J. Cell Biol. 107, 2455-2463). We report the corresponding full-length cDNA sequence and the complete primary structure of the protein, which contains a 20-residue signal peptide. The synthesis of the protein is directed by a 1450-base mRNA characterized by an unusually long 5' untranslated leader sequence and is regulated only at the transcriptional level as shown by run-off transcription assays. During differentiation, maximal expression of the protein characterizes stage II hypertrophic chondrocytes. In situ hybridization on embryo sections reveals that the protein is expressed by several structures derived from the chondrogenic lineage and that, in addition, it is a major translational product in granulocytes. High cell density largely influences the expression of the Ch21 protein in chondrocyte cultures. When embryonic avian cells of different origin are grown to confluency, the expression of the Ch21 protein is observed in only some of the cell lines. Thus quiescence per se is not the primary factor determining the expression of the protein. PMID- 1737755 TI - The yeast ribosomal protein S7 and its genes. AB - Ribosomal protein S7 of Saccharomyces cerevisiae is encoded by two genes RPS7A and RPS7B. The sequence of each copy was determined; their coding regions differ in only 14 nucleotides, none of which leads to changes in the amino acid sequence. The predicted protein consists of 261 amino acids, making it the largest protein of the 40 S ribosomal subunit. It is highly basic near the NH2 terminus, as are most ribosomal proteins. Protein S7 is homologous to both human and rat ribosomal protein S4. RPS7A and RPS7B contain introns of 257 and 269 nucleotides, respectively, located 11 nucleotides beyond the initiator AUG. The splicing of the introns is efficient. Either RPS7A or RPS7B will support growth. However, deletion of both genes is lethal. RPS7A maps distal to CDC11 on chromosome X, and RPS7B maps distal to CUP1 on chromosome VIII. PMID- 1737756 TI - A DNA exonuclease induced during meiosis of Schizosaccharomyces pombe. AB - In meiotic cells of the fission yeast Schizosaccharomyces pombe, a DNA exonuclease activity increased approximately 5-fold after premeiotic S-phase and decreased to the initial level before the meiotic divisions. We have purified this activity, designated exonuclease I, to near homogeneity. The activity co purified with a polypeptide with an apparent molecular weight of 36,000. With a linear double-stranded DNA substrate, exonuclease I degraded only the 5'-ended strand from each end to produce 3'-single-stranded tails. The enzyme also acted on nicked circular DNA with comparable affinity. The meiotic induction of exonuclease I and its mode of action, similar to that of recombination-promoting exonucleases from bacteria, suggest that exonuclease I is involved in meiotic homologous recombination in S. pombe. PMID- 1737757 TI - Identification of amino acids essential for calmodulin binding and activation of smooth muscle myosin light chain kinase. AB - Smooth muscle myosin light chain kinase (smMLCK) is a Ca(2+)-calmodulin (CaM) dependent enzyme that phosphorylates the 20-kDa light chains of myosin. In a previous study (Bagchi, I.C., Kemp, B.E., and Means, A.R. (1989) J. Biol. Chem. 264, 15843-15849), we expressed in bacteria a 40-kDa fragment of smMLCK that displayed Ca(2+)-CaM-regulated catalytic activity. Initial mutagenesis experiments indicated that Gly811 and Arg812 were important for CaM-dependent activation of this 40-kDa enzyme. We have now carried out site-directed mutagenesis within the CaM-binding domain (Ser787 to Leu813) of this enzyme to identify amino acids that are critical for CaM binding and activation. Our studies reveal that the individual mutation of several hydrophobic amino acid residues such as Leu813, Ile810, and Trp800 and the glycine residue Gly804 also resulted in a severe decrease in or complete loss of CaM binding and activation of smMLCK. The hydrophobic residue (Trp800) and the basic residue (Arg812), both of which are mandatory for CaM binding to smMLCK, occur in analogous positions within the CaM-binding domain of a number of CaM-regulated enzymes. We conclude from these results that CaM binding by smMLCK is determined by an interplay of specific hydrophobic and electrostatic interactions which appear to be conserved among various target enzymes of CaM. PMID- 1737758 TI - Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli. AB - An aldehyde dehydrogenase isozyme, ALDH3, which is strongly expressed in the stomach, may play a role in the oxidation of toxic aldehydes. Using reverse genetic approach, we cloned and characterized the cDNA and the gene for the ALDH3. The full length cDNA is 1624 base pairs (bp) in length and contains an open reading frame encoding 453 amino acid residues. The deduced amino acid sequence shows a high degree of resemblance to that of rat hepatocarcinoma ALDH. The human ALDH3 gene spans about 8 kb in length and consists of 10 exons. The putative TATA and CCAAT boxes are located in the consensus upstream distance from the transcription initiation site. Southern blot analysis of total genomic DNA argues against the proposed two-gene model for the ALDH3 isozymes (Yin, S.-J., Cheng, T.-C., Chang, C.-P., Chen, Y.-J., Chao, Y.-C., Tang, H.-S., Chang, T.-M., and Wu, C.-W. (1988) Biochem. Genet. 26, 343-360). Northern blot hybridization and analysis of PCR amplification products of cellular RNA demonstrated the existence of a high level of ALDH3 mRNA in human stomach and hepatoma cells, but a very low level in the normal liver. Expression of ALDH3 cDNA in Escherichia coli yielded a protein of 55 kDa, which exhibited kinetic properties similar to that found in ALDH3 isozyme purified from human stomach and liver, and was hybridizable with rabbit anti-human-hepatoma ALDH serum. PMID- 1737759 TI - The folding of hirudin adopts a mechanism of trial and error. AB - Reduced and denatured hirudin (65 amino acids and 3 disulfides) refolds in vitro to become an active molecule. The folding process adopts a mechanism of "trial and error" without predominant pathways. Throughout the entire folding process, the 6 cysteines were about equally involved in the disulfide shuffling. Among the first 20% of 3-disulfide species accumulated during the early phase of refolding, two-thirds were inactive and were reshuffled in the presence of thiol catalyst to regain correct disulfide pairing. When refolding was performed in the presence of strong denaturant (guanidinium chloride) without thiol catalyst, 8% of the active hirudin was obtained. This figure is close to the probability (6.7%) that would be expected from the random disulfide pairing of a molecule containing 6 sulfhydryl groups. PMID- 1737760 TI - Fluorescence energy transfer between the primer and the beta subunit of the DNA polymerase III holoenzyme. AB - We report here our initial success in using fluorescence energy transfer to map the position of the subunits of the DNA polymerase III holoenzyme within initiation complexes formed on primed DNA. Using primers containing a fluorescent derivative 3 nucleotides from the 3'-terminus and acceptors of fluorescence energy transfer located on Cys333 of the beta subunit, a donor-acceptor distance of 65 A was measured. Coupling this distance with other information enabled us to propose a model for the positioning of beta within initiation complexes. Examination of the fluorescence properties of a labeled primer with the unlabeled beta subunit and other assemblies of DNA polymerase III holoenzyme subunits allowed us to distinguish all of the known intermediates of the holoenzyme catalyzed reaction. Specific fluorescence changes could be assigned for primer annealing, Escherichia coli single-stranded DNA-binding protein binding, 3'----5' exonucleolytic hydrolysis of the primer, DNA polymerase III* binding, initiation complex formation upon the addition of beta in the presence of ATP, and DNA elongation. These fluorescence changes are sufficiently large to support future detailed kinetic studies. Particularly interesting was the difference in fluorescence changes accompanying initiation complex formation as compared to binding of DNA polymerase III holoenzyme subunit assemblies. Initiation complex formation resulted in a strong fluorescence enhancement. Binding of DNA polymerase III* led to a fluorescence quenching, and transfer of beta to primed DNA by the gamma delta complex did not change the fluorescence. This demonstrates a rearrangement of subunits accompanying initiation complex formation. Monitoring fluorescence changes with labeled beta, we have determined that beta binds with a stoichiometry of one monomer/primer terminus. PMID- 1737761 TI - Rapid ADP-evoked currents in human platelets recorded with the nystatin permeabilized patch technique. AB - "Whole-cell" patch recordings using nystatin permeabilization were made from single human platelets during application of agonists from a "puffer" pipette. In platelets clamped near the resting potential and bathed in Na+ saline, 40 microM ADP activated a transient inward current within tens of milliseconds. At -73 mV the current lasted between 0.1 and 1 s and had a peak of between 13 and 31 pA in different cells. Ion substitution experiments indicated that the channel is permeable to Na+,K+, and Ba2+ and presumably also to Ca2+, but is not permeable to Cl-. The single channel conductance was 15 pS (near the resting potential) in nominally Ca(2+)-free saline and 11 picosiemens in BaCl2 saline. Thrombin, at 1 unit/ml, did not elicit detectable currents during a 3-s application in platelets bathed in 1 mM Ca2+, Na+ saline. Under the same conditions, in fura-2-loaded cells, thrombin-evoked Ca2+ entry (monitored by Mn2+ quench) was detectable after a delay of 1.4 s. This suggests that early thrombin-evoked Ca2+ entry occurs via small conductance channels, below the resolution of the patch clamp technique, or by an electroneutral pathway. The ADP-evoked channel has the requisite speed of activation to account for the rapid Ca2+ influx observed during stopped-flow studies of agonist-evoked changes in [Ca2+]i. PMID- 1737762 TI - Calcium and catecholamine interactions with adrenal chromogranins. Comparison of driving forces in binding and aggregation. AB - The soluble core of catecholamine storage vesicles in the adrenal medulla contains high concentrations of the cations calcium (20 mM) and catecholamine (600 mM). Do these cations interact with the abundant vesicle core anionic proteins, the chromogranins? We investigated the binding of calcium and norepinephrine (NE) to bovine adrenal chromogranins by equilibrium dialysis. Both calcium and NE were bound saturably by chromogranins, with low affinity (Kd values of 1.3 x 10(-4) M and 2.1 x 10(-3) M), but high capacity (17 and 32 mol of ligand/mol of chromogranin A). Both ligands bound maximally at a pH greater than 5.5 and were displaced by competing cations in a pattern (trivalent greater than divalent greater than monovalent) consistent with electrostatic components to the interactions. Binding of calcium and NE was not impaired by prior heat denaturation of the chromogranins, and chromogranin A was involved in both binding reactions. Calcium but not NE binding was enhanced by nonpolar solvents. Temperature dependence studies indicated that calcium binding to chromogranins was largely entropy-driven, while NE binding was driven by a significantly negative (favorable) change in enthalpy (5760 cal/mol), even in the face of an unfavorable entropy. Exposure of chromogranins to calcium or NE resulted in precipitation (aggregation) as analyzed by centrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NE was a more effective chromogranin precipitant than calcium, and in combination, the NE effect was antagonized by calcium. Precipitation of chromogranins by both calcium and NE was inhibited by NaCl at ionic strengths comparable with those of the ligands. These data suggest that chromogranins bind and are precipitated by calcium and NE at affinities compatible with their in situ concentrations, but that the interactions exhibit different thermodynamic driving forces. Furthermore, NE may trigger an enthalpy driven conformational change in chromogranins, resulting in aggregation. PMID- 1737763 TI - Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver. AB - The mitogen-activated 70K S6 kinase has an apparent Km for 40 S ribosomal subunits of 0.25 microM. The apparent Km for a synthetic peptide derived from the carboxyl terminus of S6 and containing all of the in vivo sites of phosphorylation was 2.5-fold higher. A number of shorter peptides revealed that the substrate recognition determinants for the preferred site of phosphorylation, Ser236, reside in a seven-amino acid stretch of S6, residues 231-217. Critical to recognition is a block of 3 consecutive arginines, especially Arg231 and Arg233. In contrast, replacement of Ser235 or the preferred site of phosphorylation, Ser236, with alanine has little effect on the apparent Km. Based on this data the consensus recognition sequence would be Arg-(Arg)-Arg-X-X-Ser-X. A number of kinases known to phosphorylate S6, including cAMP-dependent protein kinase and protein kinase C and the 92K S6 kinase II, were also tested for their ability to phosphorylate a decapeptide containing all the critical recognition determinants. Finally, a synthetic peptide containing a putative 70K S6 kinase autoinhibitory domain did not serve as a substrate for the enzyme but did inhibit its activity, although much less effectively than a synthetic peptide containing all the recognition determinants. PMID- 1737764 TI - A mutation in the consensus ATP-binding sequence of the RecD subunit reduces the processivity of the RecBCD enzyme from Escherichia coli. AB - We have constructed a mutant form of the RecBCD enzyme from Escherichia coli with a lysine to glutamine change in the consensus ATP-binding sequence in the RecD subunit (Korangy, F., and Julin, D.A. (1992a, 1992b) J. Biol. Chem., 1727-1732; 1733-1740). We compare here the kinetics of double-stranded DNA-dependent ATP hydrolysis by the mutant (RecBCD-K177Q) and wild-type enzymes. We included heparin to trap enzyme not bound to DNA, or the single-stranded DNA-binding (SSB) protein from Escherichia coli to prevent the enzyme from binding to single stranded DNA products and partially single-stranded reaction intermediates. The ATP hydrolysis kinetics in either case show a rapid burst phase followed by a slower second phase. The wild-type enzyme hydrolyzes an amount of ATP about equal to the DNA nucleotide concentration in the rapid phase. The amount of ATP hydrolyzed by the RecBCD-K177Q enzyme in the burst is about 8-10-fold lower than the wild-type, in the presence of either heparin or SSB. The burst magnitude of the wild-type enzyme with heparin is proportional to the size of the DNA from about 1,420 to 22,400 base pairs whereas that of the mutant is independent of the DNA size. The wild-type enzyme completely degrades a 6,250-base pair DNA substrate with no partially degraded molecules visible on agarose gels. RecBCD K177Q enzyme reaction mixtures in the presence of SSB protein contain a heterogeneous mixture of partially degraded molecules of 2,000-5,000 base pairs. These results indicate that the RecBCD-K177Q enzyme is less processive than the wild-type enzyme. PMID- 1737765 TI - Iron-catalyzed oxidative modification of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. Structural and functional changes. AB - As a variety of eukaryotic cells age, the specific activity of glucose-6 phosphate dehydrogenase (Glu-6-PDH) declines as much as 50%. Because of the central role of this enzyme in metabolism, it is important to define factors responsible for this loss in enzyme activity. We report that Glu-6-PDH from Leuconostoc mesenteroides is rapidly inactivated by micromolar concentrations of Fe2+ and H2O2. Inactivation correlated with the formation of one carbonyl functionality/enzyme subunit, indicating that inactivation is the result of site specific oxidative modification. Our results suggest that Fe2+ binds to the glucose 6-phosphate binding site and that interaction of the enzyme-bound Fe2+ with H2O2 leads to the oxidative modification of amino acids essential for enzyme activity. Partially inactivated enzyme remained predominantly in the dimeric form, and no change in the apparent affinity of the remaining active subunits for substrate was observed. Partial inactivation did, however, lead to a decrease in the thermal stability of the remaining activity. This decrease in thermal stability could be largely overcome by the addition of glucose 6-phosphate. Thus, although exposure to H2O2 and Fe2+ results in the irreversible inactivation of Glu-6-PDH, the resulting modification is selective, leads to the formation of heterodimers of both active and inactive subunits, and does not appear to cause large scale structural changes. Our results demonstrate the inherent susceptibility of Glu-6-PDH from L. mesenteroides to modification by an oxidation system known to exist in vivo. An assessment of the physiological significance of Fe(2+)-catalyzed oxidation of Glu-6-PDH awaits extension of these studies to mammalian sources known to accumulate less active or inactive forms of the enzyme as a function of age. PMID- 1737766 TI - Systems analysis of the tricarboxylic acid cycle in Dictyostelium discoideum. I. The basis for model construction. AB - A steady-state model of the tricarboxylic acid cycle was constructed using a dynamic systems analysis computer program, METASIM. The model was based on radioactive tracer analyses which provided flux relationships and compartmented metabolite concentrations. Ten of the enzymes modeled were purified and characterized from Dictyostelium discoideum. Although experimentally determined enzyme mechanisms and constants were used in the model, Vmax values were found to be unreliable, i.e. they did not reflect enzyme activity in vivo. This value was therefore calculated as the only unknown in each enzyme kinetic equation and called Vvivo, to distinguish it from Vmax determined in vitro. PMID- 1737767 TI - Systems analysis of the tricarboxylic acid cycle in Dictyostelium discoideum. II. Control analysis. AB - A steady-state computer model of the tricarboxylic cycle in Dictyostelium discoideum was analyzed using metabolic control theory. The steady state had variations of less than 0.04% over the last half of the simulation for both metabolite concentrations and fluxes. Metabolite and flux control coefficients were determined by varying enzymatic activities within 2% of their initial values and simulating the responses of metabolite concentrations and fluxes to these changes. Under these conditions, summation properties were met for most metabolite and all flux control coefficients. Maximum flux control coefficients were found for succinate dehydrogenase (0.35), malic enzyme (0.24), and malate dehydrogenase (-0.18). Comparable control was found for the reaction supplying pyruvate (0.14) and for the sum of the input amino acids (0.43), which serve as an energy source for D. discoideum. The time-dependent processes by which a new steady state was established were examined after increasing malic enzyme or malate dehydrogenase activities. This provided a method for an analysis of the mechanisms by which the observed control coefficients were generated. In addition, the effects of increasing the stimuli within 5-20% of the original enzyme activity were examined. Under these conditions, more typical of experimental stimuli and measurable responses, the metabolic model failed to return to steady state, and thus summation properties were not met. Whether "true" steady states ever occur or whether metabolic control theory can be applied in vivo is discussed. PMID- 1737768 TI - Inactivation of thrombin by murine peritoneal macrophages. AB - We recently showed that murine peritoneal macrophages cultured in vitro express potent prothrombinase activity (Lindahl, U., Pejler, G., Bogwald, J., and Seljelid, R. (1989) Arch. Biochem. Biophys. 273, 180-188). In the present report, we demonstrate that the macrophages also express anticoagulant activity by inactivating the thrombin that is formed due to the action of the prothrombinase. Addition of exogenous purified thrombin to the macrophage cultures resulted in inactivation of the enzyme at a maximum rate of approximately 5 micrograms/h/10(6) cells. The inactivation appeared to be specific for thrombin, since neither Factor Xa, chymotrypsin, nor trypsin, three serine proteases exhibiting homology with thrombin, were inactivated by the macrophages. Thrombin inactivating activity was not secreted into the culture medium. Inhibitors of endocytosis did not decrease the rate by which thrombin was inactivated, suggesting that internalization of the coagulation factor was not required. In contrast, the thrombin-inactivating activity was strongly inhibited by the polycation Polybrene. Anion-exchange chromatography of extracts obtained after Triton X-100-solubilization of the macrophages demonstrated that the thrombin inactivating activity exhibited a high negative charge. Incubation of the thrombin-inactivating activity recovered after anion-exchange chromatography with unlabeled thrombin, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, showed that thrombin was proteolytically cleaved into defined fragments. Similar proteolytic fragments were obtained when 125I-labeled thrombin was added to macrophage cultures. Degradation of thrombin was blocked by phenylmethanesulfonic fluoride, an inhibitor of serine proteases, but not by inhibitors of other classes of proteases. Thrombin that had been chemically modified at its active site was degraded at the same rate by the macrophages as active thrombin. Taken together, these findings indicate that the murine macrophages express surface-bound serine protease activity that specifically inactivates thrombin by proteolytic cleavage. The significance of thrombin inactivating activity in relation to the involvement of macrophage procoagulant activity in the immune response is discussed. PMID- 1737769 TI - Formation of a free acyl adenylate during the activation of 2-propylpentanoic acid. Valproyl-AMP: a novel cellular metabolite of valproic acid. AB - A study of the activation of valproic acid (2-n-propylpentanoic acid) by a soluble extract of rat liver mitochondria in the presence of ATP, CoASH, and MgCl2 revealed that, in addition to valproyl-CoA, an unknown UV-absorbing compound is formed which is the sole product when CoASH is omitted from the incubation mixture. The unknown compound, which was purified by high performance liquid chromatography, was identified as valproyl adenylate (valproyl-AMP) by mass spectrometry and by its enzymatic conversion to valproyl-CoA in the presence of CoASH. Valproyl-AMP exists, at least partially, in a free, not-enzyme-bound form. Its rate of formation is linear with time and increases 5-fold when the pH is decreased from 8 to 6.8. Valproyl-AMP was also identified when the metabolism of valproate was investigated with rat liver mitochondria and rat hepatocytes. Since the synthesis of valproyl-AMP is inhibited by octanoate, medium-chain acyl CoA synthetase (EC. 6.2.1.2) may be responsible for its formation. This study establishes that during the activation of valproic acid to valproyl-CoA free valproyl-AMP is formed which is a novel cellular metabolite of valproic acid. PMID- 1737770 TI - The structure of tracheobronchial mucins from cystic fibrosis and control patients. AB - Tracheobronchial mucin samples from control and cystic fibrosis patients were purified by gel filtration chromatography on Sephacryl S-1000 and by density gradient centrifugation. Normal secretions contained high molecular weight (approximately 10(7] mucins, whereas the cystic fibrosis secretions contained relatively small amounts of high molecular weight mucin together with larger quantities of lower molecular weight mucin fragments. These probably represent products of protease digestion. Reducing the disulfide bonds in either the control or cystic fibrosis high molecular weight mucin fractions released subunits of approximately 2000 kDa. Treating these subunits with trypsin released glycopeptides of 300 kDa. Trypsin treatment of unreduced mucin also released fragments of 2000 kDa that could be converted into 300-kDa glycopeptides upon disulfide bond reduction. Thus, protease-susceptible linkages within these mucins must be cross-linked by disulfide bonds so that the full effects of proteolytic degradation of mucins remain cryptic until disulfide bonds are reduced. Since various combinations of protease treatment and disulfide bond reduction release either 2000- or 300-kDa fragments, these fragments must represent important elements of mucin structure. The high molecular weight fractions of cystic fibrosis mucins appear to be indistinguishable from control mucins. Their amino acid compositions are the same, and various combinations of disulfide bond reduction and protease treatment release products of identical size and amino acid composition. Sulfate and carbohydrate compositions did vary considerably from sample to sample, but the limited number of samples tested did not demonstrate a cystic fibrosis-specific pattern. Thus, tracheobronchial mucins from cystic fibrosis and control patients are very similar, and both share the same generalized structure previously determined for salivary, cervical, and intestinal mucins. PMID- 1737771 TI - Involvement of phage T5 tail proteins and contact sites between the outer and inner membrane of Escherichia coli in phage T5 DNA injection. AB - The penetration of phage T5 DNA into the Escherichia coli envelope takes place through ion channels (Boulanger, P., and Letellier, L. (1992) J. Biol. Chem. 267, 3168-3172). To identify putative phage protein(s) involved in the formation of these channels, E. coli cells were infected at 37 degrees C with radioactively labeled phage and their envelopes were fractionated. After a flotation gradient, proteins belonging to the phage tail were recovered both in fractions containing the contact sites between the inner and outer membranes and in the outer membrane. The electrophoretic banding pattern of phage proteins indicates that the contact sites were enriched in the protein pb2. Moreover, infected cells were significantly enriched in contact sites as compared to intact cells. There was no enrichment of contact sites and very little radioactivity was found in this fraction and in the outer membrane when the cells were infected at 4 degrees C (i.e. under conditions where the phage does not inject its DNA). These results suggest that both contact sites and pb2 may play a central role in the translocation of phage T5 DNA. PMID- 1737772 TI - Selective antagonism of thyroid hormone action by retinoic acid. AB - Thyroid hormone (T3) and retinoic acid (RA) regulate gene transcription by binding to similar nuclear receptors. We have investigated the effects of RA, alone and in combination with T3, on a number of T3-responsive genes expressed in rat pituitary adenoma cells. Like T3, RA increased growth hormone gene expression in GH3 as well as in GH1 cells, and the effects of the hormones were additive. In contrast, RA alone had little effect on the expression of the beta 2 form of T3 receptor (TR beta 2), which is markedly decreased by T3. Remarkably, however, RA completely inhibited the down-regulation of TR beta 2 mRNA by T3. RA alone also had little effect on TR beta 1 mRNA, but its presence did not prevent the up regulation of TR beta 1 mRNA by T3. The target-gene-specific antagonism of T3 action by RA was observed in both GH cell lines. Nuclear run-on assays demonstrated that the effect occurred at the level of TR beta 2 gene transcription, and the half-life of the TR beta 2 mRNA was unchanged by RA in the presence or absence of T3. The half-maximal RA dose required for these effects suggested that they were mediated by one or more of the nuclear receptors for RA. Indeed, GH3 cells contain mRNAs encoding the three distinct RA receptor subtypes, alpha, beta, and gamma, as well as retinoid X receptors. These results demonstrate that the effects of RA and T3 on gene expression are dependent on the nature of the target gene as well as on hormonal interactions, probably at the level of the receptors. PMID- 1737773 TI - Evidence that the hormone-binding domain of the mouse glucocorticoid receptor directly represses DNA binding activity in a major portion of receptors that are "misfolded" after removal of hsp90. AB - After dissociation of cytosolic heteromeric glucocorticoid receptor complexes by steroid, salt, and other methods, only 35-60% of the dissociated receptors can bind to DNA-cellulose. The DNA-binding and non-DNA-binding forms of the dissociated receptors have the same Mr and are phosphorylated to the same extent (Tienrungroj, W., Sanchez, E. R., Housley, P. R., Harrison, R. W., and Pratt, W. B. (1987) J. Biol. Chem. 262, 17347-17349). The basis for the different DNA binding activities is unknown, but the DNA-binding fraction of the receptor has a more basic pI than the non-DNA-binding fraction (Smith, A. C., Elsasser, M. S., and Harmon, J. M. (1986) J. Biol. Chem. 261, 13285-13292). We have separated the non-DNA-binding state of the receptor from the DNA-binding state and then cleaved it with trypsin and chymotrypsin. We find that the 15-kDa tryptic fragment derived from the non-DNA-binding state of the dissociated receptor is fully competent in binding DNA, whereas the 42-kDa chymotryptic fragment containing both the hormone-binding and DNA-binding domains does not bind DNA. Trypsin cleavage of the molybdate-stabilized untransformed receptor also yields a 15-kDa fragment that is fully competent in binding DNA. Reducing agents do not restore DNA-binding to the non-DNA-binding fraction of the receptor and the hormone binding domain can be separated from the DNA-binding domain on nonreducing gel electrophoresis. These results argue that the two domains are not linked by disulfide bridges, and they are consistent with the proposal that there are two least energy states of folding after dissociation of hsp90. A significant portion of the receptors is "misfolded" in such a manner that the steroid binding domain is directly preventing DNA-binding activity. PMID- 1737774 TI - Aspartylglycosaminuria in a non-Finnish patient caused by a donor splice mutation in the glycoasparaginase gene. AB - Aspartylglycosaminuria is a lysosomal storage disease caused by deficient activity of glycoasparaginase (EC 3.5.1.26), and it occurs with a high frequency among Finns. We have recently shown that the molecular defect in all Finnish aspartylglycosaminuria patients examined to date consists of two single base changes in the heavy chain of glycoasparaginase (Mononen, I., Heisterkamp, N., Kaartinen, V., Williams, J. C., Yates, J. R., III, Griffin, P. R., Hood, L. E., and Groffen, J. (1991) Proc. Natl. Acad. Sci U.S.A. 88, 2941-2945). This is the first report on the identification of the molecular defect causing aspartylglycosaminuria in a patient of non-Finnish origin. Total RNA from fibroblasts of a black American aspartylglycosaminuria patient was isolated, first-strand cDNA was synthesized, and the cDNA encoding glycoasparaginase was amplified by the polymerase chain reaction. The patient's mRNA nucleotide sequence was different from the normal sequence by a deletion of 134 nucleotides at positions 807-940. Nucleotide sequence analysis of the normal glycoasparaginase gene demonstrated that the deletion corresponded precisely to a 134-base pair exon. Moreover, analysis of the splice sites demonstrated a single base change, G to T, that altered the donor splice site of the exon deleted in the patient's mRNA. This change led to an exon-skipping event resulting in a frame shift and generation of a stop codon. PMID- 1737775 TI - Global conformational changes in allosteric proteins. A study of Escherichia coli cAMP receptor protein and muscle pyruvate kinase. AB - One of the basic features in allosteric regulation involves long range transduction of information. Based on crystallographic data on protein systems that are regulated by allosteric mechanisms, a global conformational change has always been observed. It is, therefore, important and useful to correlate the cooperativity of global structural change with the mode of binding of the regulatory ligand. Two systems were chosen for study, namely Escherichia coli cAMP receptor protein and muscle pyruvate kinase, which show negative and positive cooperativity in the binding of allosteric ligands, respectively. Quantitative titration of the global structural change, monitored by a high precision analytical gel chromatography technique, was conducted as a function of allosteric effector concentration. The results obtained for cAMP receptor protein show that the protein undergoes contraction upon binding of cAMP. The decreases in Stokes radius associated with complex formation are 0.1 +/- 0.1 and 0.7 +/- 0.1 A when one and two cAMP-binding sites are filled, respectively. The results for the pyruvate kinase system show a concerted structural change that quantitatively match the predicted behavior based on equilibrium constants derived from the analysis of steady state kinetic data by a two-state model. Hence, for these two systems, these results show that negative and positive cooperativity are correlated with sequential and concerted modes of structural change, respectively. PMID- 1737776 TI - Reduced S-adenosylhomocysteine hydrolase. Kinetics and thermodynamics for binding of 3'-ketoadenosine, adenosine, and adenine. AB - S-Adenosylhomocysteine hydrolase (SAHase) was resolved into apoenzyme and NAD+ by acidic ammonium sulfate treatment. The apoenzyme was catalytically inactive, but could be reconstituted to active enzyme with NAD+. Reduced SAHase (ENADH) that was prepared by reconstitution of the apoenzyme with NADH was catalytically inactive. ENADH was oxidized by 3'-ketoadenosine to active SAHase. The recovery of activity paralleled the oxidation of enzyme-bound NADH. The association rate constant for ENADH and 3'-ketoadenosine was 6.1 x 10(2) M-1 s-1, and the dissociation rate constant was calculated to be 4 x 10(-7) s-1. This association rate constant was considerably smaller than the association rate constant for adenosine and SAHase (greater than 10(7) M-1 s-1). However, the observed pseudo first-order rate constant for reaction of 3'-ketoadenosine with ENADH (0.6 s-1 with 1 mM 3'-ketoadenosine) approached kcat for the hydrolytic reaction (1.2 s 1). Thus, bound 3'-ketoadenosine probably reacted sufficiently rapidly with ENADH to be considered a kinetically competent intermediate. The dissociation constants of SAHase for adenosine and 4',5'-dehydroadenosine, substrates for the enzyme, were 9 and 14 microM, respectively. In contrast, the dissociation constants of ENADH for 3'-ketoadenosine and 4',5'-dehydro-3'-ketoadenosine, intermediates of the catalytic reaction, were significantly lower with values of 600 and 300 pM, respectively. The equilibrium constant for reduction of enzyme-bound NAD+ in the absence of an adenosine analogue, as estimated from cyanide binding studies, was 10-fold more favorable than that for free NAD+. ENADH was highly fluorescent (emission maximum 428 nm, excitation 340 nm) with a quantum yield that was six times that of free NADH. Since SAHase reduced by adenosine was not highly fluorescent, enzyme-bound intermediates quenched the fluorescence of enzyme-bound NADH. Adenosine and adenine quenched the fluorescence of ENADH. Cyanide formed a complex with SAHase that was analogous to ENADH. Adenine stabilized this complex sufficiently that addition of 65 microM adenine and 25 mM cyanide to SAHase caused total complex formation with loss of over 95% of the catalytic activity. PMID- 1737777 TI - High and low affinity receptors for human interleukin for DA cells/leukemia inhibitory factor on human cells. Molecular characterization and cellular distribution. AB - Radioiodinated recombinant human interleukin DA (HILDA)/leukemia inhibitory factor (LIF) purified from conditioned medium of Chinese hamster ovary transfected cells enabled the identification of specific receptor sites on a variety of human cell types. Using low concentrations (up to 500 pM) of the ligand iodinated at a high specific radioactivity, high affinity receptors (equilibrium dissociation constant Kd in the range of 30-100 pM) were first demonstrated. They were expressed at low levels by human peripheral blood monocytes but not by lymphocytes, NK cells, granulocytes, and platelets. The myelomonocytic cell line THP1 as well as the T lymphoma cell line HSB2 and the lymphoblastoid B cell line DAB were also receptor-negative. In contrast, most of the non-lymphoid tumoral cell lines tested, including melanomas, neuroblastomas, and carcinomas, expressed high affinity HILDA/LIF receptors at variable levels (Bmax from 20 to 600 sites/cell). The kinetics of HILDA/LIF high affinity binding to the choriocarcinoma JAR cell line were characterized at 4 degrees C with association and dissociation rate constants of k1 = 2.2 10(9) M-1 min-1 and k-1 = 0.0084 min-1, respectively, corresponding to a steady-state dissociation constant k1/k-1 = 3.8 pM. The subsequent use of higher concentrations of HILDA/LIF labeled at a lower specific radioactivity enabled the identification of a low affinity component on several cell lines (Kd in the range of 1-4 nM; Bmax from 1,000 to 5,000 sites/cell). On JAR cells, this low affinity component was characterized by association and dissociation rate constants at 4 degrees C of k1 = 7.3 10(7) M-1 min-1 and k-1 = 0.19 min-1, respectively (k-1/k1 = 2.6 nM). Affinity cross linking of HILDA/LIF to JAR cells showed two cross-linked species under both reducing and nonreducing conditions corresponding to receptor species of 120 and 250 kDa, respectively. Whereas both bands had similar intensities under high affinity conditions, the higher band predominated under low affinity conditions. Our data suggest that the 250-kDa chain could constitute the low affinity binding component whereas the association of both 250- and 120-Da subunits would form the high affinity structure. PMID- 1737778 TI - Gi down-regulation as a mechanism for heterologous desensitization in adipocytes. AB - Prolonged incubation of rat adipocytes with (-)N6-phenylisopropyl adenosine (PIA) (an A1 adenosine receptor agonist) leads to down-regulation of each of the three subtypes of Gi (Green, A., Johnson, J. L., and Milligan, G. (1990) J. Biol. Chem. 265, 5206-5210). To determine whether other inhibitors of adenylylcyclase would have similar actions, we incubated adipocytes in primary culture with PIA, prostaglandin E1 (PGE1), or nicotinic acid. After various times cells were homogenized, and crude membrane fractions were analyzed on Western blots using antipeptide antisera to alpha- and beta-subunits of G-proteins (SG1 (which binds to alpha i1 and alpha i2), I3B (which binds to alpha i3), BN2 (binds to beta subunits) and CS1 (recognizes forms of alpha s)). PIA and PGE1 caused approximately 90% down-regulation of alpha i1 and alpha i3, and about 50% loss of alpha i2 and beta-subunits. In contrast, nicotinic acid at concentrations up to 1 mM had no effect on levels of any of these Gi subtypes. None of the compounds altered levels of either a 43- or 47-kDa form of alpha s. PIA caused about a 50% decrease in binding of [3H]DPCPX (an A1 adenosine receptor antagonist), indicating adenosine receptor down-regulation; however, neither PGE1 nor nicotinic acid treatment altered [3H]DPCPX binding. None of the treatments affected the activity of adenylylcyclase when measured in the presence of 100 microM forskolin and 10 mM Mn2+, indicating that the catalytic subunit of adenylylcyclase is not altered. To determine whether Gi down-regulation results in heterologous desensitization, we incubated adipocytes with maximally effective concentrations of PIA (300 nM), PGE1 (3 microM), or nicotinic acid (1 mM) for 4 days. The cells were then washed and incubated for an additional 30 min with various concentrations of these compounds to determine their ability to inhibit lipolysis. PIA caused a (marked) decrease in the sensitivity of the cells to both PIA and PGE1, thus indicating heterologous desensitization. Similarly, PGE1 decreased the sensitivity of the cells to both PGE1 and PIA, again demonstrating heterologous desensitization. In contrast, prolonged incubation with nicotinic acid decreased the sensitivity of the cells to nicotinic acid but had no effect on the sensitivity of the cells to PIA. Adenylylcyclase in membranes from PGE1 treated cells showed decreased sensitivity to inhibition by PIA. In contrast, adenylylcyclase showed normal sensitivity to PIA in membranes from nicotinic acid treated cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1737779 TI - GTP but not GDP analogues promote association of ADP-ribosylation factors, 20-kDa protein activators of cholera toxin, with phospholipids and PC-12 cell membranes. AB - ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins initially identified by their ability to enhance cholera toxin ADP-ribosyltransferase activity in the presence of GTP. ARFs have been purified from both membrane and cytosolic fractions. ARF purified from bovine brain cytosol requires phospholipid plus detergent for high affinity guanine nucleotide binding and for optimal enhancement of cholera toxin ADP ribosyltransferase activity. The phospholipid requirements, combined with a putative role for ARF in vesicular transport, suggested that the soluble protein might interact reversibly with membranes. A polyclonal antibody against purified bovine ARF (sARF II) was used to detect ARF by immunoblot in membrane and soluble fractions from rat pheochromocytoma (PC-12) cell homogenates. ARF was predominantly cytosolic but increased in membranes during incubation of homogenates with nonhydrolyzable GTP analogues guanosine 5'-O-(3 thiotriphosphate), guanylyl-(beta gamma-imido)-diphosphate, and guanylyl-(beta gamma-methylene)-diphosphate, and to a lesser extent, adenosine 5'-O-(3 thiotriphosphate). GTP, GDP, GMP, and ATP were inactive. Cytosolic ARF similarly associated with added phosphatidylserine, phosphatidylinositol, or cardiolipin in GTP gamma S-dependent fashion. ARF binding to phosphatidylserine was reversible and coincident with stimulation of cholera toxin-catalyzed ADP-ribosylation. These observations may reflect a mechanism by which ARF could cycle between soluble and membrane compartments in vivo. PMID- 1737780 TI - Two novel Streptomyces protein protease inhibitors. Purification, activity, cloning, and expression. AB - In contrast to the Gram-negative bacteria, Gram-positive bacteria such as Streptomyces lack a mucopolysaccharide cell wall which allows them to produce and secrete a variety of proteins directly into their environment. In an effort to understand and eventually exploit the synthesis and secretion of proteins by Streptomyces, we identified and characterized two naturally occurring abundantly produced proteins in culture supernatants of Streptomyces lividans and Streptomyces longisporus. We purified these 10-kDa proteins and obtained partial amino acid sequence information which was then used to design oligonucleotide probes in order to clone their genes. Analysis of the sequence data indicated that these proteins were related to each other and to several other previously characterized Streptomyces protein protease inhibitors. We demonstrate that both proteins are protein protease inhibitors with specificity for trypsin-like enzymes. The presumptive signal peptidase cleavage sites and subsequent aminopeptidase products of each protein are characterized. Finally, we show that the cloned genes contain all of the information necessary to direct synthesis and secretion of the proteins by Streptomyces spp. or Escherichia coli. PMID- 1737781 TI - Effects of gamma-carboxyglutamic acid and epidermal growth factor-like modules of factor IX on factor X activation. Studies using proteolytic fragments of bovine factor IX. AB - Factor IX is a vitamin K-dependent zymogen of a serine protease. The NH2-terminal half of the molecule consists of a Ca(2+)-binding gamma-carboxyglutamic acid (Gla)-containing module and two modules homologous to the epidermal growth factor (EGF) precursor. To elucidate the role of these non-catalytic modules of factor IXa beta in factor X activation, we have isolated and characterized fragments of bovine factor IX, containing one or both of the EGF-like modules as well as these modules linked to the Gla module. The fragments were used as inhibitors of factor IXa beta-mediated factor X activation in a plasma clotting system and in systems with purified components of the Xase complex. Fragments consisting of either the two EGF-like modules of factor IX linked together or the NH2-terminal EGF-like module alone were found to inhibit factor Xa generation both in the presence and absence of the cofactor, factor VIIIa. Moreover, a fragment consisting of the corresponding modules of factor X had a similar effect. We therefore propose that factor IXa beta and factor X interact directly through their EGF-like modules on or in the vicinity of a phospholipid surface. We have also found that the isolated Gla module of factor IX inhibits the formation of factor Xa both in the presence and absence of phospholipid but not in the absence of factor VIIIa. Our results are compatible with a model of the Xase complex, in which both the serine protease part and the Gla module of factor IXa beta interact with factor VIIIa. PMID- 1737782 TI - Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. AB - In this report we describe the identification and characterization of a novel tumor-associated receptor-type tyrosine kinase (hek). We produced a monoclonal antibody (III.A4) that detected a novel glycoprotein on the immunizing pre-B cell acute lymphoblastic leukemia cell line (LK63). This antigen was shown to be expressed sporadically on hemopoietic tumor cell lines and on ex vivo tumors. However, using antibody staining, the molecule was undetectable on normal tissues. Further biochemical characterization showed this molecule (hek) to be a phosphoroprotein. This observation taken together with the tumor-associated nature of hek expression suggested that hek might be a receptor-type protein tyrosine kinase. This was demonstrated by affinity purification of hek. In in vitro kinase experiments the purified hek protein was autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein. Purified hek was subjected to N-terminal amino acid sequence analysis which showed that hek had a unique N terminus. Amino acid sequence determination of peptides from a V8 protease digest of hek yielded one 21-amino acid stretch of sequence which showed close homology with the eph subfamily of protein tyrosine kinases. These studies show hek to be a novel human tumor-associated protein tyrosine kinase, which by analogy with previously characterized protein tyrosine kinase proto-oncogenes, may have a role in tumorigenesis. PMID- 1737783 TI - The folding and cell surface expression of CD4 requires glycosylation. AB - Human CD4, a monomeric T cell surface glycoprotein, is required for T helper cell activation and is also the receptor for the human immunodeficiency virus. There have been conflicting reports as to whether glycosylation of CD4 is required for its cell surface expression. To clarify the effect of glycosylation on surface expression, folding, and intracellular sorting of CD4, we generated a series of mutant cDNAs in which one, the other, or both glycosylation recognition sites were eliminated. Using in vitro transcription and translation we confirmed that both potential glycosylation sites of CD4 were utilized. Transient expression of the mutants in HeLa cells demonstrated that glycosylation at either site was necessary and sufficient for cell surface expression. Finally, we showed that unglycosylated CD4 produced in HeLa cells was incorrectly folded and retained intracellularly, probably in the endoplasmic reticulum. PMID- 1737784 TI - The deduced sequence of the transcription factor TFIIIA from Saccharomyces cerevisiae reveals extensive divergence from Xenopus TFIIIA. AB - TFIIIA is an RNA polymerase III transcription factor that binds to the internal control region of the 5 S RNA gene as the first step in the assembly of a transcription complex. We have identified the gene encoding TFIIIA from Saccharomyces cerevisiae. Protein synthesized in vitro from the cloned gene has the same size, DNA-binding properties, and transcription factor activity as does purified yeast TFIIIA. Examination of the deduced sequence of the 50-kDa yeast transcription factor revealed the presence of nine zinc-finger motifs, a characteristic of Xenopus TFIIIA. Although the conservation of these nine putative DNA-binding domains is striking, the amino acid sequence throughout the corresponding fingers of the yeast and amphibian TFIIIAs has diverged extensively and in many instances the spacing between the residues that coordinate the zinc ions differs between the two proteins. A unique feature of the yeast protein is an 81-amino acid domain interrupting the repeated zinc-finger motifs between fingers 8 and 9. Additionally, the yeast and amphibian proteins differ in both the size and sequence of the amino- and carboxyl-terminal domains flanking the zinc fingers. The gene encoding yeast TFIIIA is present in single copy in the S. cerevisiae genome and is essential for cell viability. A carboxyl-terminal truncated form of the protein containing 4.5 zinc-finger motifs retains the ability to bind to DNA but is no longer active in promoting transcription in vitro. PMID- 1737785 TI - Thyroid hormone stimulation of NADPH P450 reductase expression in liver and extrahepatic tissues. Regulation by multiple mechanisms. AB - The role of thyroid hormone in regulating the expression of the flavoprotein NADPH cytochrome P450 reductase was studied in adult rats. Depletion of circulating thyroid hormone by hypophysectomy, or more selectively, by treatment with the anti-thyroid drug methimazole led to a 75-85% depletion of hepatic microsomal P450 reductase activity and protein in both male and female rats. Thyroxine substantially restored P450 reductase activity at a dose that rendered the thyroid-depleted rats euthyroid. Microsomal P450 reductase activity in several extrahepatic tissues was also dependent on thyroid hormone, but to a lesser extent than in liver (30-50% decrease in kidney, adrenal, lung, and heart but not in testis from hypothyroid rats). Hepatic P450 reductase mRNA levels were also decreased in the hypothyroid state, indicating that the loss of P450 reductase activity is not a consequence of the associated decreased availability of the FMN and FAD cofactors of P450 reductase. Parallel analysis of S14 mRNA, which has been studied extensively as a model thyroid-regulated liver gene product, indicated that P450 reductase and S14 mRNA respond similarly to these changes in thyroid state. In contrast, while the expression of S14 and several other thyroid hormone-dependent hepatic mRNAs is stimulated by feeding a high carbohydrate, fat-free diet, hepatic P450 reductase expression was not increased by this lipogenic diet. Injection of hypothyroid rats with T3 at a supraphysiologic, receptor-saturating dose stimulated a major induction of hepatic P450 reductase mRNA that was detectable 4 h after the T3 injection, and peaked at approximately 650% of euthyroid levels by 12 h. However, this same treatment stimulated a biphasic increase in P450 reductase protein and activity that required 3 days to reach normal euthyroid levels. T3 treatment of euthyroid rats also stimulated a major induction of P450 reductase mRNA that was maximal (12-fold increase) by 12 h, but in this case no major increase in P450 reductase protein or activity was detectable over a 3-day period. Together, these studies establish that thyroid hormone regulates P450 reductase expression by pretranslational mechanisms. They also suggest that other regulatory mechanisms, which may involve changes in P450 reductase protein stability and/or changes in the translational efficiency of its mRNA, are likely to occur. PMID- 1737786 TI - Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. AB - Ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine delta-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine delta-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine delta-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine delta-aminotransferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine delta-aminotransferase mRNA. By contrast, only 2/24 had normal amounts of ornithine delta-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients. PMID- 1737787 TI - Membrane-associated carbonic anhydrase from rat lung. Purification, characterization, tissue distribution, and comparison with carbonic anhydrase IVs of other mammals. AB - Carbonic anhydrase (CA) IV was purified to homogeneity from rat lung microsomal and plasma membranes. The single N-terminal amino acid sequence showed 55% similarity to that reported for human CA IV. A monospecific antibody to the 39 kDa rat enzyme that cross-reacts on Western blots with CA IVs from other mammalian species was produced in rabbits. Digestion of rat lung enzyme with endoglycosidase (peptide-N-glycosidase F) reduced the Mr to 36,000, suggesting that rat CA contains one N-linked oligosaccharide chain. All of eight additional mammalian CA IVs that were examined also contained oligosaccharide chains, as evidenced by reduction in Mr from 52,000 (cow, sheep, and rabbit), 42,000 (pig, guinea pig, and dog), and 39,000 (mouse and hamster) to 36,000 after treatment of the respective lung microsomal membranes with peptide-N-glycosidase F. The 36-kDa human enzyme showed no change in molecular mass with this treatment. Thus, the human CA IV is the exceptional one in lacking carbohydrate. Rat lung CA IV was found to be relatively resistant to sodium dodecyl sulfate and to be anchored to membranes by a phosphatidylinositol-glycan linkage; both properties were found to be shared by other mammalian CA IVs. Western blot analysis indicated distribution of CA IV in rat tissues other than kidney and lung where it was previously known to be present. CA IV was particularly abundant in rat brain, muscle, heart, and liver, all locations where the CA IV enzyme was not known to be present previously. None was detected in rat skin or spleen. PMID- 1737788 TI - An array of insulin-activated, proline-directed serine/threonine protein kinases phosphorylate the p70 S6 kinase. AB - This study characterizes the insulin-activated serine/threonine protein kinases in H4 hepatoma cells active on a 37-residue synthetic peptide (called the SKAIPS peptide) corresponding to a putative autoinhibitory domain in the carboxyl terminal tail of the p70 S6 kinase as well as on recombinant p70 S6 kinase. Three peaks of insulin-stimulated protein kinase active on both these substrates are identified as two (possibly three) isoforms of the 40-45-kDa erk/microtubule associated protein (MAP)-2 kinase family and a 150-kDa form of cdc2. Although distinguishable in their substrate specificity, these protein kinases together with the p54 MAP-2 kinase share a major common specificity determinant reflected in the SKAIPS peptide: the requirement for a proline residue immediately carboxyl terminal to the site of Ser/Thr phosphorylation. In addition, however, at least one peak of insulin-stimulated protein kinase active on recombinant p70, but not on the SKAIPS peptide, is present although not yet identified. MFP/cdc2 phosphorylates both rat liver p70 S6 kinase and recombinant p70 S6 kinase exclusively at a set of Ser/Thr residues within the putative autoinhibitory (SKAIPS peptide) domain. erk/MAP kinase does not phosphorylate rat liver p70 S6 kinase, but readily phosphorylates recombinant p70 S6 kinase at sites both within and in addition to those encompassed by the SKAIPS peptide sequences. Although the tryptic 32P-peptides bearing the cdc2 and erk/MAP kinase phosphorylation sites co-migrate with a subset of the sites phosphorylated in situ in insulin stimulated cells, phosphorylation of the p70 S6 kinase by these proline-directed protein kinases in vitro does not reproducibly activate p70 S6 kinase activity. Thus, one or more erk/MAP kinases and cdc2 are likely to participate in the insulin-induced phosphorylation of the p70 S6 kinase. In addition to these kinases, however, phosphorylation of the p70 S6 kinase by other as yet unidentified protein kinases is necessary to recapitulate the multisite phosphorylation required for activation of the p70 S6 kinase. PMID- 1737789 TI - Gene conversion confined to a direct repeat of the acceptor splice site generates allelic diversity at human glycophorin (GYP) locus. AB - The glycophorin locus (GYP) on the long arm of chromosome 4 encodes antigens of the MNSs blood group system and displays considerable allelic variation among human populations. The genomic structure and organization of a variant glycophorin allele specifying a novel Miltenberger (Mi)-related phenotype, MiX, were examined. This variant probably arose from a gene conversion event involving a direct repeat of the acceptor splice site. Southern blot analysis indicated that MiX gene derived its 5' and 3' portions from glycophorin B or delta gene but its internal part from glycophorin A or alpha gene. Genomic sequences encompassing the rearranged regions of the MiX gene were amplified by single copy polymerase chain reaction. Direct DNA sequencing showed that during the formation of MiX gene, a short stretch of alpha exon III with a donor splice site has replaced a silent sequence in the delta gene containing a cryptic acceptor splice site. The upstream delta-alpha breakpoint is flanked by the direct repeats of the acceptor splice site, whereas the down-stream alpha-delta breakpoint is located in the adjacent intron. This segmental transfer produced a new composite exon whose expression not only transactivated a portion of silent sequence but also created intraexon and interexon hybrid junctions that characterize the antigenic specificities of MiX glycophorin. The identification of MiX as yet another delta alpha-delta hybrid different from MiIII and MiVI in gene conversion sites suggests that shuffling of expressed and unexpressed sequences through particular genomic DNA motifs has been an important mechanism for shaping the antigenic diversity of MNSs blood group system during evolution. PMID- 1737790 TI - DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. AB - Mitochondrial transcription factor 1 (mtTF1) is the only accessory protein known to be required for accurate and efficient promoter recognition by mammalian mitochondrial RNA polymerase. It activates transcription by binding immediately upstream of transcriptional start sites and shows an inherent flexibility in primary DNA sequence requirement. By application of a purification strategy designed for human and mouse mtTF1, a protein resembling mtTF1 was recently isolated from yeast mitochondria; its size (19 kDa), DNA-binding properties, and amino acid composition suggest identity to HM, a previously described abundant protein of yeast mitochondria. Both human and yeast proteins show a general ability to wrap or condense and unwind DNA in vitro and bend DNA at specific sequences. Recent determinations of the amino acid sequences of the human and yeast proteins reveal that both contain domains homologous to the nuclear high mobility group (HMG) proteins which have been implicated in diverse functions such as chromatin compaction and transcription stimulation. The ability to unwind and bend DNA may be fundamental to the documented roles of the mammalian protein in mitochondrial DNA transcription and replication priming and suggests a similar function for the yeast protein in yeast mitochondria. PMID- 1737791 TI - DNA binding properties of an HMG1-related protein from yeast mitochondria. AB - The DNA binding properties of ABF2, an abundant protein found in the mitochondria of the yeast Saccharomyces cerevisiae have been examined in detail. ABF2 is closely related to the vertebrate high mobility group protein HMG1 and like HMG1, ABF2 will introduce negative supercoils into a relaxed, double-stranded circular DNA molecule in cooperation with a DNA topoisomerase. Additionally, ABF2 binds approximately 5-10 times more tightly to negatively supercoiled DNA than to relaxed circular or linear DNA. Although ABF2 binds to most random double stranded sequences with roughly equal affinity, its binding within certain key regulatory regions is qualitatively quite different. First, ABF2 binding induces a distinct pattern of DNA bending within the chromosomal origin of DNA replication, ARS1. Second, ABF2 binding to all nuclear replication origins tested, in addition to a critical mitochondrial promoter and replication origin, is clearly nonrandom as visualized by DNase1 footprinting. Analysis of the sequences found within these regions as well as competition experiments with synthetic DNA molecules suggest that site-specific DNA binding may be accomplished by the phased distribution of short stretches of poly(dA), which exclude ABF2 binding. These patterns of ABF2 DNA binding suggest a role for the protein in genome organization and site-specific regulation of transcription or DNA replication. PMID- 1737792 TI - A triple helix-forming oligonucleotide-intercalator conjugate acts as a transcriptional repressor via inhibition of NF kappa B binding to interleukin-2 receptor alpha-regulatory sequence. AB - Oligonucleotide-directed triplex formation within upstream regulatory sequences is envisioned as a potential tool for gene inhibition. However, this approach requires that triple helix-forming oligonucleotides are chemically modified, so that the triplex is stable under physiological conditions. Here, we have compared several chemical modifications of an oligonucleotide, targeted to a natural 15 base pair homopyrimidine.homopurine sequence located in the upstream regulatory region of the gene encoding the interleukin-2 receptor alpha chain (p55, IL-2 R alpha). Methylation of the cytosines strongly stabilized the triplex. Further attachment of an intercalating agent (acridine) dramatically increased the stability of the triplex, as assessed by Tm measurements or by band shift assays. Furthermore, the acridine-derivatized oligonucleotide was more efficient in competing away high affinity DNA-binding proteins, as assessed by restriction enzyme inhibition assays. Using a novel footprinting assay, we have further shown that the interaction of the methylcytosine-substituted, acridine-derivatized oligonucleotide with a plasmidic target, harboring the IL-2 R alpha regulatory region, remains highly sequence specific, occurs at physiological pH and is independent of the superhelicity of the plasmid. Acridine derivatization did not impair the exquisite target specificity of triplex formation, since the derivatized oligonucleotide inhibited the binding of nuclear proteins to the overlapping NF kappa B enhancer sequence on an IL-2 R alpha target and not on the related human immunodeficiency virus long terminal repeat target. Finally, the oligonucleotide inhibited the NF kappa B-dependent tax-induced transcriptional activation of the IL-2 R alpha chloramphenicol acetyltransferase construct in live cells, whereas it did not have any effect on a human immunodeficiency virus long terminal repeat chloramphenicol acetyltransferase construct. We conclude that this modified oligonucleotide acts as a transcriptional repressor for the IL 2 R alpha gene via triple helix formation with regulatory sequences. PMID- 1737793 TI - Triacylglycerol hydrolysis in isolated hepatic endosomes. AB - Three endosomal compartments including the compartment for uncoupling receptor and ligand (CURL), multivesicular bodies (MVB), and a putative recycling fraction (retrosomes) were isolated from rat liver homogenates fifteen minutes after a bolus injection of very low density lipoprotein (VLDL) was delivered into a femoral vein. Assays for enzyme markers indicate a minimal contamination with either lysosomes or Golgi. The increase in specific activity of the radiolabeled ligand (VLDL) during the isolation procedure from homogenate to MVB, demonstrates a 200-250-fold purification of this organelle. All three fractions have the ability to catabolize triacylglycerol substrate both as triolein and as VLDL triacylglycerol. Furthermore, incubation of isolated endosomes following injection of endogenously labeled VLDL demonstrate their ability to hydrolyze VLDL triacylglycerol in situ. Three distinct lipolytic pH optima were found at pH 5.5, 7.1, and 8.6. The effects of serum, MgCl2, CaCl2, NaCl, sodium dodecyl sulfate, bile acids, and antibody to hepatic triacylglycerol lipase on the individual endosome fractions demonstrated distinct lipolytic activities in the different compartments. Results indicate that both an endosomal neutral lipase as well as hepatic triacylglycerol lipase make a significant contribution to lipolytic processing of endocytosed lipoproteins prior to their resecretion of further processing in hepatic lysosomes. PMID- 1737794 TI - Secreted and cellular proteochondroitin sulfates of a human B lymphoblastoid cell line contain different protein cores. AB - Proteoglycans of the human B lymphoblastoid cell line LICR-LON-HMy2 were metabolically labeled with [35S]sulfate. High-density fractions of 35S-labeled material separated by CsCl gradient ultracentrifugation were further purified by anion exchange chromatography and gel filtration. Two proteoglycans, isolated from cell lysates and culture supernatants, were characterized by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in combination with enzymatic degradation. Treatment with chondroitinase AC completely degraded the glycosaminoglycan moiety of the proteoglycans. Three to 4 chondroitin sulfate chains (average molecular mass = 26 kDa) were estimated for each of the two proteoglycans. Differences between the proteochondroitin sulfates (CSPG) were observed in the content of N-linked oligosaccharides. After chondroitinase AC treatment the resulting band in SDS-PAGE of the secreted CSPG was sensitive to treatment with endoglycosidase F (Endo F) which further reduced the molecular mass from 30 to 21.5 kDa, whereas the band of the cellular CSPG after chondroitinase AC treatment (molecular mass = 30 kDa) remained resistant to Endo F treatment. The composition of amino acids was different in the protein cores, suggesting differences in the primary structure. Both CSPG contained a high percentage of glycine and serine. For both CSPG a molecular mass of approximately 135 kDa was deduced from the hydrodynamic sizes of the glycosaminoglycan chains obtained after alkaline/borohydride treatment and the migration of the protein/oligosaccharide complexes in SDS-PAGE. 75% of all [35S]sulfate-labeled molecules were found in the culture supernatant and 25% in the cellular fraction. 35S-Labeled material in the culture supernatant consisted exclusively of intact CSPG, whereas 35S-Labeled molecules in the cellular preparation consisted largely of free chondroitin sulfate chains. Only 8.3% of the cellular material, isolated from the microsomal fraction, was intact CSPG. In pulse-chase experiments maximal secretion of CSPG was found after 4 h, comprising approximately 40% of totally synthesized CSPG. From these experiments we tentatively conclude that a small proportion of CSPG synthesized by LICR-LON-HMy2 cells is membrane-associated, a larger portion is secreted, and another portion is intracellularly degraded. PMID- 1737795 TI - Selective inactivation of the Arg-Gly-Asp-Ser (RGDS) binding site in von Willebrand factor by site-directed mutagenesis. AB - In order to assess the requirement for the Arg-Gly-Asp-Ser (RGDS) consensus adhesion sequence in von Willebrand factor (vWF) for vWF binding to platelets and endothelial cells, point mutations were introduced into this sequence by site directed mutagenesis. A glycine to alanine substitution yielded RADS-vWF, while an aspartate to glutamate substitution resulted in RGES-vWF. Recombinant RADS-vWF and RGES-vWF, purified from transformed Chinese hamster ovary cells, were compared with recombinant wild type vWF (WT-vWF) in functional assays with platelets and human umbilical vein endothelial cells (HU-VECs). High molecular weight RADS-vWF and RGES-vWF multimers inhibited binding of 125I-vWF to a mixture of insolubilized native type I and III collagen and competed effectively with 125I-vWF for binding to formalin-fixed platelets in the presence of ristocetin, indicating functional collagen and platelet glycoprotein Ib binding. However, RADS-vWF and RGES-vWF were unable to displace the binding of 125I-vWF to thrombin or ADP-activated platelets. The attachment of HUVECs to either RADS-vWF or RGES vWF coated surfaces was reduced and spreading was almost completely inhibited, compared with WT-vWF. We conclude that point mutations of the RGDS sequence in vWF selectively impair binding to platelet glycoprotein IIb/IIIa and the HUVEC vitronectin receptor. PMID- 1737796 TI - Human estrogen receptor mutants with altered estrogen and antiestrogen ligand discrimination. AB - A structural characteristic of many antiestrogens (AEs) is a bulky side chain with basic or polar functional groups that may interact with charged and polar amino acids near the hormone-binding site in the estrogen receptor. Recently, we have identified Cys530 as the residue of the human estrogen receptor that is the site of covalent labeling by aziridine analogs of estrogens (Es) and AEs (Harlow, K. W., Smith, D. N., Katzenellenbogen, J. A., Greene, G. L., and Katzenellenbogen, B. S. (1989) J. Biol. Chem. 264, 17476-17485). Since the aziridine function is on the bulky side chain of these ligands, Cys530 must be at or near the site of those side chain interactions. To probe these interactions, we have, by site-directed mutagenesis, made mutant human estrogen receptors in which charged and polar amino acids near Cys530 are changed (Glu523 to Gln, Lys529 and Lys531 to Gln, Asn532 to Asp, and Asp538 to Asn) so as to alter charge with minimal steric alteration. These receptors were expressed in mammalian (Chinese hamster ovary or COS-1) cells and assayed for their binding affinity for Es and AEs, their interaction with estrogen-responsive element DNA, and their ability to activate or suppress transcription of estrogen-responsive reporter genes. Two of the estrogen receptor mutants, KKN-QQD (mutation of Lys529, Lys531, and Asn532 to Gln529, Gln531, and Asp532, respectively) and KK-QQ (mutation of Lys529 and Lys531 to Gln529 and Gln531, respectively), in which the local charge is changed from +2 to -1 or 0, respectively, display an affinity for estradiol (E2) 5-10 times lower than that of the wild-type receptor, which is attributable to an enhanced rate of E2 dissociation. Although these mutant receptors have reduced affinity for a variety of Es, they retain unaltered affinity for AE. The profiles of transcriptional activation of reporter genes by various concentrations of E2 show that these two mutants (KKN-QQD and KK-QQ) require 40- and 15-fold higher E2 concentrations, respectively, to achieve half-maximal activity. In contrast, mutants E523Q and D538N, with changes at amino acids further from Cys530, were unaltered in their hormone binding and transactivation activity by E or AE. Interestingly, the AEs 4-hydroxytamoxifen, LY 117018, U 23469M, and ICI 164384 were 15-30-fold more effective in inhibiting E2-stimulated transcription by mutants KKN-QQD and KK-QQ compared to the wild-type receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1737797 TI - Phosphorylation of brush border myosin I by protein kinase C is regulated by Ca(2+)-stimulated binding of myosin I to phosphatidylserine concerted with calmodulin dissociation. AB - Brush border myosin I from chicken intestine is phosphorylated in vitro by chicken intestinal epithelial cell protein kinase C. Phosphorylation on serine and threonine to a maximum of 0.93 mol of P/mol of myosin I occurs within an approximately 20 kDa region at the end of the COOH-terminal tail of the 119-kDa heavy chain. The effects of Ca2+ on myosin I phosphorylation by protein kinase C are complex, with up to 4-fold stimulation occurring at 0.5-3 microM Ca2+, and up to 80% inhibition occurring at 3-320 microM Ca2+. Phosphorylation required that brush border myosin I be in its phosphatidylserine vesicle-bound state. Previously unknown Ca2+ stimulation of brush border myosin I binding to phosphatidylserine vesicles was found to coincide with Ca2+ stimulation of phosphorylation. A myosin I proteolytic fragment lacking approximately 20 kDa of its tail retained Ca(2+)-stimulated binding, but showed reduced Ca(2+) independent binding. Ca(2+)-dependent phosphatidylserine binding is apparently due to the concomitant phosphatidylserine-promoted, Ca(2+)-induced dissociation of up to three of the four calmodulin light chains from myosin I. Four highly basic putative calmodulin-binding sites in the Ca(2+)-dependent phosphatidylserine binding region of the heavy chain were identified based on the similarity in their sequence to the calmodulin- and phosphatidylserine-binding site of neuromodulin. Calmodulin dissociation is now shown to occur in the low micromolar Ca2+ concentration range and may regulate the association of brush border myosin I with membranes and its phosphorylation by protein kinase C. PMID- 1737798 TI - Conversion of monocyte chemoattractant protein-1 into a neutrophil attractant by substitution of two amino acids. AB - The small cytokine monocyte chemoattractant protein-1 has structural similarity to the neutrophil chemoattractant interleukin-8, but each protein is specific in attracting its own target cell. To investigate the structural basis of this cell type specificity, we have developed an Escherichia coli expression system for the monocyte chemoattractant and mutagenized selected amino acid residues to ones found at the corresponding positions of interleukin-8. We find that a double mutation of tyrosine 28 and arginine 30 to leucine and valine, respectively, causes a drastic decrease in chemotactic activity toward monocytes with the appearance of a novel (interleukin-8-like) neutrophil chemotactic activity. Computer graphic analysis predicts that, with the double substitution, a putative receptor binding groove of the monocyte chemoattractant protein would become topographically similar to that of interleukin-8. We therefore postulate that one or both of these amino acid residues are part of the binding contact of these small cytokines and their receptors. PMID- 1737799 TI - Diverse biologic properties imparted by the c-fgr proto-oncogene. AB - The c-fgr proto-oncogene specifies a nonreceptor protein-tyrosine kinase, p55c fgr, a member of the src family. In the present study, we have mutagenized c-fgr to mimic alterations found at the 3' end of the v-fgr oncogene and have investigated the biologic effects of normal and mutant p55c-fgr expression. Genes lacking 10 or 13 codons at the 3' end, as well as a gene encoding phenylalanine instead of tyrosine at codon 523, were potent oncogenes when transfected into NIH 3T3 cells. Specific enzymatic activities of the more highly transforming gene products were 3-4-fold greater than that of p55c-fgr. In vivo, the amount of tyrosine phosphorylation of cellular proteins was directly proportional to potency in focus-forming assays. These findings are the first to identify highly transforming mutations of the c-fgr proto-oncogene. The proto-oncogene was also active in transforming assays, demonstrably greater than that of a kinase deficient mutant. Foci arising in c-fgr-transfected cultures expressed abundant enzyme that was normal by a number of criteria. In addition, growth rates for cells expressing p55c-fgr were restricted, as compared with cells expressing a kinase-deficient protein or cells transformed by proteins with high specific enzymatic activities. Thus, enzymatically active p55c-fgr can simultaneously activate transforming and growth inhibitory pathways. PMID- 1737800 TI - Regulated expression of alpha 2,6-sialyltransferase by the liver-enriched transcription factors HNF-1, DBP, and LAP. AB - Tissue-specific carbohydrate structures are thought to result from the selective expression of specific terminal glycosyltransferases responsible for their synthesis. However, little is known about the regulation of the expression of these enzymes. Previous analysis of the distribution of one such enzyme, beta galactoside alpha 2,6-sialyltransferase, revealed that its expression is tissue restricted, with highest levels being found in the liver. Examination of the gene suggested that its expression is regulated at the level of transcription by multiple promoters, one of which is strongly active in the liver. In this present work, an analysis of the liver-restricted promoter was undertaken to identify the promoter elements necessary for liver-restricted expression. Footprinting studies, 5' deletion analysis, and site-directed mutagenesis identified two cis elements which were potentially important in the tissue-specific expression of this promoter. One of these elements contains a consensus binding site for the liver-enriched transcription factor hepatocyte nuclear factor-1 alpha, while the other is a consensus binding site for the liver-specific factors D-binding protein and liver-enriched transcriptional activator protein. Expression vectors containing cDNAs of these factors are capable of trans-activating transcription of the alpha 2,6ST promoter, demonstrating their ability to regulate transcription of this promoter. Together, these results suggest that tissue specific glycosylation can be regulated at the level of transcription by the same factors involved in the expression of a number of other tissue-specific genes. PMID- 1737801 TI - Analysis of phosphoprotein p19 by liquid chromatography/mass spectrometry. Identification of two proline-directed serine phosphorylation sites and a blocked amino terminus. AB - p19 is a highly conserved 19-kDa cytosolic protein that undergoes phosphorylation in mammalian cells upon activation of several distinct signal transduction pathways. Its expression is widespread but developmentally regulated. To determine the in vivo phosphorylation site(s) of p19, the protein was purified from bovine brain and resolved into the unphosphorylated form (p19) and a mixture of the two predominant phospho-forms (pp19). Proteolytic fragments of p19 and pp19 were examined by liquid chromatography/mass spectrometry (LC/MS). We detected ion masses corresponding to fragments spanning the entire amino acid sequence as deduced from the cDNA except for those predicted to contain an unmodified amino terminus. Instead, the digests revealed ions corresponding to peptides lacking the initiator methionine and containing an N-acetylated alanine at the amino terminus. The analysis of pp19, but not that of p19, revealed two sets of ions representing peptides whose m/z values differed by 80 atomic mass units, the incremental mass of a phosphate residue. These putative phosphate bearing peptides were sensitive to alkaline phosphatase treatment. Using combined trypsin and V8 protease digestions, the phosphorylation sites were mapped to Ser 25 and Ser-38, in the peptides Leu-Ile-Leu-Ser*-Pro-Arg and Phe-Pro-Leu-Ser*-Pro Pro-Lys, respectively. Interestingly, both phosphoserines are in a very similar sequence context, suggesting that a single proline-directed serine protein kinase, possibly p34cdc2, is responsible for phosphorylation of both sites in vivo. PMID- 1737802 TI - A multicomponent protein of a fission yeast that promotes joint molecule formation from homologous DNAs. AB - We developed a quantitative assay ("homologous pairing gel assay") adequate for the purification of the activity promoting the formation of joint molecules, an intermediate of homologous recombination ("homologous pairing"). With this assay, one can measure the extent of homologous pairing between a single-stranded DNA and a strand of 3H-labeled double-stranded DNA by crude enzyme preparations. Since the total activity did not significantly change during the sporulation process, we tried to purify the activity from a whole cell extract of mitotic cells of a fission yeast, (Schizosaccharomyces pombe). Through quantitative assaying of a single fraction or of mixed fractions, we obtained three fractions, all of which were required for the maximum level of the ATP-independent homologous pairing: Fractions 65, 100, and 30. In Fractions 100 and 30, polypeptides of approximately 100 and approximately 30 kDa (the 100- and 30-kDa polypeptides), respectively, were the sole detectable components. Fraction 65 contained a polypeptide of approximately 65 kDa (the 65-kDa polypeptide) as the major component and also small amounts of the 30- and 100-kDa polypeptides. Fraction 65 by itself promoted homologous pairing, but the reaction was saturated at a level of approximately 20% of the maximum level achieved with the recA protein. Even when added in excess, Fraction 30 or 100 alone did not promote detectable homologous pairing. A mixture of Fractions 65 and 100 at a rather strict optimum ratio only promoted homologous pairing, the level being 50-70% that with the recA protein, suggesting a stoichiometric complex of these polypeptides as the active form. Fraction 30 alone did not enhance the reaction with Fraction 65, but stimulated homologous pairing promoted by the optimum mixture of Fractions 65 and 100 to the maximum level achieved with the recA protein. Therefore, the homologous pairing-promoting protein from the fission yeast is likely to be a multicomponent protein. PMID- 1737803 TI - Identification, characterization, and resolution of the in vivo phosphorylated form of the D1 photosystem II reaction center protein. AB - The chloroplast-encoded D1 protein of oxygenic photosynthetic organisms is a component of the photosystem II reaction center. Previously, we detected an electrophoretic variant of D1 which was generated in vivo in granal-localized reaction centers in a light dependent manner (Callahan, F.E., Ghirardi, M.L., Sopory, S.K., Mehta, A.M., Edelman, M., and Mattoo, A.K. (1990) J. Biol. Chem. 265, 15357-15360). In the present study, we identify this modified form as phosphorylated D1. The in vivo phosphorylation occurs on a threonine residue(s) localized within 1 kDa from the N terminus and is identical to the phosphorylation of D1 catalyzed in vitro by a redox-regulated thylakoid-bound protein kinase. While virtually all of the D1 protein present in thylakoids can be phosphorylated in vitro, the steady-state level of phosphorylated D1 in vivo varies with light intensity and did not exceed 20% of the total D1 under the conditions of this study. PMID- 1737804 TI - Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase gene and its expression in mammalian cells. PMID- 1737805 TI - Characterisation of health and social development. AB - The relative performance of less developed countries in their health, demographic and economic sectors was assessed by means of comparative indices constructed with the help of a factor analysis. This approach reduces the problems usually associated with such indices, like the arbitrary weighting of their components. PMID- 1737806 TI - Determinants of child mortality in south-west Uganda. AB - Anthropometric and sociodemographic variables were taken from 4320 children in a baseline survey carried out in March-April 1988 in the district of Mbarara, south west Uganda. After 12 months a follow-up survey assessed the mortality of the children during the preceding year. Lack of ownership of cattle, recent arrival in the village, using candles for lighting, being of birth order higher than 5 and having a father with less than 8 years of schooling were significantly associated with child mortality. The addition of mid-upper arm circumference significantly improved the logistic model of socioeconomic variables and mortality and did not diminish the predictive power of socioeconomic variables in relation to increased mortality. This suggests that nutritional status and specific socioeconomic factors are both, independently, important predictors of child mortality. PMID- 1737807 TI - The influence of religious affiliation on surname repetition in marriages in Tiszaszalka, Hungary. AB - The repeated-pairs of surnames in marriages (RP) approach is applied to the population of Tiszaszalka in north-eastern Hungary. The results indicate that: (1) lineage-like behaviour in mate choice results in population subdivision in both the Catholics and the Protestants of the village; (2) unlike in some other Tiszahat villages, the isonymous and the repeating unions in Tiszaszalka occur in different lineages so, in neither of these subpopulations are isonymous and repeating unions monopolised by a few lineages; (3) religious affilitation influences the mating structure of the population as measured by RP summary scores. PMID- 1737808 TI - Changes in age at marriage of women in rural north India. AB - There has been a dramatic increase in age at marriage for women in a rural area of north India. Age at marriage rose from under 12 years before 1930 to about 19 years in 1988, mainly as a result of socioeconomic development and advances in education of women. PMID- 1737809 TI - Given name relationships support surname 'genetics': a note and correction. AB - Analysis of a further four samples of first names in the index of marriages registered in England and Wales in the first 3 months of 1975 support the claim that there is no significant difference of 'between' versus 'within' registration district Ri. Since given names show none of the localisation seen in surnames, the surname geography is ascribable to genetic rather than cultural factors of personal naming. The correct formulations for coefficient of relationship by isonymy are given. PMID- 1737810 TI - Coital frequency and twinning. A comment. PMID- 1737811 TI - Measurement of post-partum amenorrhoea in Bangladesh. AB - Reported information on the duration of post-partum amenorrhoea usually shows considerable number preference, particularly at 6-monthly intervals. This paper presents a technique for smoothing such amenorrhoea data using a modified exponential curve. An attempt has also been made to estimate the average number of months a mother is expected to remain amenorrhoeic. PMID- 1737812 TI - Birth order and health status in a British national sample. PMID- 1737813 TI - Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women. AB - The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity. PMID- 1737814 TI - Breast-feeding in London, 1905-19. AB - Medical Officer of Health reports for London boroughs, 1900-19, are analysed to determine the incidence of neonatal breast-feeding, duration of lactation, reasons for early supplementation and premature weaning, and their relationship with infant mortality. In a sample of 222,989 infants, breast-feeding rates were very high. Over 90% were breast-fed in the first month, almost 80% at 3 months, and over 70% at 6 months. The poorest boroughs had the highest rates of neonatal breast-feeding, but also a higher incidence of early supplementation and premature weaning. There was a significant positive correlation between breast feeding and infant mortality due to poor maternal diet and health, poor nutritional quality of supplementary and substitute foods, and the use of an unhygienic feeding bottle. Energetic campaigns to counteract these problems probably contributed to the fall of infant mortality in this period. PMID- 1737815 TI - Seasonal patterns of spontaneous abortion. AB - The presence of a seasonal pattern of spontaneous abortion in the United States was found using data from the two most recent cycles of the National Survey of Family Growth (USA). The pattern was bimodal with peaks in March and August. PMID- 1737816 TI - Response reliability of demographic data: a longitudinal study in Sri Lanka. AB - Response consistency was examined by linking the records of women interviewed in the 1982 Sri Lanka Contraceptive Prevalence Survey with records from the same individuals followed up 3 years later. Seventy-eight percent of women reported identical year of birth in the two surveys, but only 58% were consistent for age at marriage. Data on sterilisation and number of children born were highly reliable, but wives' reports on husband's age and education were relatively weak. Multivariate analysis of the effects of socioeconomic factors on consistency in age reporting confirms that education is the most influential factor related to consistency, followed by religion and husband's occupation. PMID- 1737817 TI - Correlation between subsequent lengths of postpartum amenorrhoea in a prospective study of breast-feeding women in rural Bangladesh. AB - The relationship between subsequent lengths of lactational amenorrhoea for individual women in a prospective study of breast-feeding women in Bangladesh was studied. The data indicate that previous length of amenorrhoea has significant predictive value for the subsequent length of amenorrhoea. Information on previous experience with lactational amenorrhoea should be therefore incorporated into guidelines for the introduction of family planning during lactation. PMID- 1737818 TI - Effect of son mortality on contraceptive practice in Bangladesh. AB - This study based on the 1975-76 Bangladesh Fertility Survey showed that the mortality of sons, and not daughters, was associated with a lower rate of female contraceptive initiation of use and a higher rate of discontinuation. PMID- 1737819 TI - Fertility and suicide rates: a time series analysis in the United States. AB - In a time series study of the USA from 1933 to 1984, fertility rates were associated with the suicide rates of those aged 15-44. The higher the fertility rate the lower the suicide rate for these age groups, for both whites and non whites, and for both men and women. The results were seen as supporting Durkheim's theory of suicide. PMID- 1737820 TI - Turning bad luck into good. The alchemy of Willem Kolff, the first successful artificial kidney, and the artificial heart. PMID- 1737821 TI - Starch strikes back. PMID- 1737822 TI - A patient who got darker on zidovudine therapy. PMID- 1737823 TI - Management of aortic dissection after coronary artery bypass. PMID- 1737824 TI - Pain and lumps in the female breast. PMID- 1737825 TI - In the best interests of Helga Wanglie. PMID- 1737826 TI - Squamous cell carcinoma of the skin. PMID- 1737827 TI - Psychosexual disorders in children and adolescents. PMID- 1737828 TI - The sexual abuse of male children and adolescents: a review of current research. AB - Inevitably, in a wide ranging review, there will be some important omissions. The main difficulties in assessing the available information have been the lack, in so many studies, of analysis along gender lines, the lack of control groups, and, in many instances, too small sample size. Despite these limitations there has, over the past decade, been an upsurge of interest in and awareness of the significance of the sexual abuse of boys. It permits us to identify a number of important trends and to draw certain conclusions. Firstly, the scale of the sexual abuse of boys is much greater than was believed 10 years ago. There is no reason to think this is simply an artifact of definition, or information gathering, or indeed of an increased willingness to recognize abusive behaviour between children, even though these will all have an effect. Whilst the trend is clear, the actual prevalence rate is difficult to determine, with a reported range of between 3% and 31%. A current 'best guess' suggests contact abuse in the range of 2-5% in the male population. As each study controls for its own definition of abuse, the narrowing in the ratio of boys to girls abused can be accepted as quite reliable, and additional evidence of a delayed recognition effect. Retrospective community evidence shows 1 boy is abused for every 2-4 girls abused. In contrast, the highest clinical ratios are for 1 boy to every 4 girls. Those who work with runaways, male child prostitutes, or child and adolescent psychiatric inpatient units appear particularly likely to encounter abused boys. Secondly, a variety of explanations have been advanced to explain the apparent under-reporting or under-detection of the sexual abuse of boys. Prominent among them have been the boy's fears of disbelief and of being labelled homosexual. Police patterns of reporting extra-familial abuse may mask its extent from protection or health agencies, which is important because extra-familial abuse does appear to be more common in boys, especially older boys, than girls. Although there has been some diminution of the cultural denial that girls can be abused, a parallel decrease of denial regarding boys has lagged behind. This is particularly true of father-son and of the much less common mother-son abuse. It is plausible that certain 'alertors' are more relevant for boys. The recent development of aggressive behaviour, homophobic anxiety, co-abuse of a sibling and abusing behaviour in particular deserve consideration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1737829 TI - Childhood temperament. PMID- 1737830 TI - Early-onset anorexia nervosa and related eating disorders. PMID- 1737831 TI - The underlying nature of specific language impairment. PMID- 1737832 TI - Autoimmune anti-HIV-1gp120 antibody with antiidiotype-like activity in sera and immune complexes of HIV-1-related immunologic thrombocytopenia. AB - Autoimmune antiidiotype-like antibody (Ab2) directed against anti-HIV-1gp120 (Ab1) was found in high titer in the sera of 10 consecutive homosexual and 11 narcotic addict HIV-1-related immunologic thrombocytopenia (HIV-1-ITP) patients, was barely detectable in 10 nonthrombocytopenic HIV-1 sero-positive individuals, and was not detectable in 5 normal subjects by use of a solid-phase RIA. Reactivity of autologous Ab2 for Ab1 was 4-120-fold greater than Ab2 for homologous Ab1. Affinity-purified Ab2 did not block the binding of affinity purified Ab1 to its HIV-1gp120 epitopes on immunoblot, indicating the absence of "internal image" antiidiotype. Both Ab1 and Ab2 are precipitable from sera with polyethylene glycol (PEG) and present in a macromolecular complex that is excluded by gel filtration on G200 and contains IgG, IgM, C3, and the anti F(ab')2 antiidiotype-like complex. PEG-precipitable complexes bind to platelets in a saturation-dependent manner. Neither affinity-purified Ab1 nor Ab2 binds to platelets. However, the combination of Ab1 and Ab2 (preincubated for 2 h at 22 degrees C) binds to platelets in a saturation-dependent manner at an optimum ratio range of 10-20:1. Ab2 reactivity correlates with serum PEG-precipitable immune complex level (r = 0.91; P less than 0.001) and with thrombocytopenia (r = 0.89; P less than 0.001). We suggest that the anti-HIV-1gp120 antiidiotype-like complex contributes to the markedly elevated platelet Ig and C3 level of HIV-1 ITP patients and propose that this may contribute to their thrombocytopenia. PMID- 1737833 TI - Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix. AB - Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of 125I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of LDL tested (1-100 micrograms), LDL retention by the monolayers increased more than fourfold. 125I-labeled LDL binding to extracellular matrix increased when LPL was added directly to the matrix or was added to the basolateral side of the endothelial cell monolayers. Increased LDL binding required the presence of LPL and was not associated with LDL aggregation. LPL also increased VLDL, but not HDL, retention. Monoclonal anti-LPL IgG decreased both VLDL and LDL retention in the presence of LPL. Lipoprotein transport across the monolayers increased during hydrolysis of VLDL triglyceride (TG). In the presence of LPL and VLDL, VLDL transport across the monolayers increased 18% and LDL transport increased 37%. High molar concentrations of oleic acid to bovine serum albumin (3:1) in the medium increased VLDL transport approximately 30%. LDL transport increased 42% when oleic acid was added to the media. Therefore, LPL primarily increased retention of LDL and VLDL. A less remarkable increase in lipoprotein transport was found during hydrolysis of TG containing lipoproteins. We hypothesize that LPL-mediated VLDL and LDL retention within the arterial wall potentiates conversion of these lipoproteins to more atherogenic forms. PMID- 1737834 TI - Feedback inhibition of insulin gene expression by insulin. AB - To examine the possible involvement of insulin and glucose in regulation of pancreatic islet gene expression, hyperinsulinemic (insulin infusion 4.1 mU/kg per min) clamps were performed for 12 h in rats at two different levels of glycemia (either 3 or 8 mM). A control group received a saline infusion for 12 h. At the end of the 12-h study period, pancreatic RNA was extracted, proinsulin and amylin mRNAs were measured on total RNA, and glucokinase and glucose transporter (GLUT-2) mRNAs were measured on poly(A)+ RNA by dot blot analysis. In insulin infused hypoglycemic rats, there was a 58% decrement in proinsulin mRNA (P less than 0.01) relative to levels in controls, with no change in amylin, glucokinase, or islet GLUT-2 mRNAs. In insulin-infused hyperglycemic rats, there was a comparable decrement (44%, P less than 0.01) in proinsulin mRNA and a smaller decrement in GLUT-2 mRNA (32%, P less than 0.05), with no change in amylin or glucokinase mRNAs relative to levels in control animals. These studies suggest that insulin has a negative feedback inhibitory effect on its own synthesis. The mechanism of inhibition is unknown. It could be a direct effect of insulin on its own transcription, or alternatively an indirect effect mediated by humoral or neural factors. Sustained hyperinsulinemia may lead to suppression of normal islet beta cells and may contribute to the ultimate hypoinsulinemia of noninsulin dependent diabetes mellitus. PMID- 1737835 TI - Noradrenergic inhibition of canine gallbladder contraction and murine pancreatic secretion during stress by corticotropin-releasing factor. AB - Gastrointestinal secretory and motor responses are profoundly altered during stress; but the effects of stress and its mediator(s) on the two major gut functions, exocrine pancreatic secretion and gallbladder motility, are unknown. We therefore developed two animal models that allowed us to examine the effects of acoustic stress on canine gallbladder contraction and restraint stress on rat exocrine pancreatic secretion. Acoustic stress inhibited cholecystokinin-8 (CCK)- and meal-induced gallbladder contraction, and restraint stress inhibited basal and CCK/secretin-stimulated pancreatic secretion. These inhibitory responses were mimicked by cerebral injection of corticotropin-releasing factor (CRF) and abolished by the CRF antagonist, alpha-helical CRF-(9-41). The effects of stress and exogenous CRF were simulated by intravenous infusion of norepinephrine but prevented by ganglionic, noradrenergic, and alpha-adrenergic but not beta adrenergic receptor blockade. Vagotomy, adrenalectomy, and--in rats- hypophysectomy did not alter the effects produced by stress and CRF. These results indicate that endogenous CRF released in response to different stressors in distinct species inhibits canine gallbladder contraction and murine exocrine pancreatic secretion via activation of sympathetic efferents. Release of norepinephrine appears to be the final common pathway producing inhibition of biliary and pancreatic digestive function during stress mediated by cerebral CRF. PMID- 1737836 TI - Diagnostic value of a synthetic peptide derived from Echinococcus granulosus recombinant protein. AB - A specific monoclonal antibody (MAb; EG 02 154/12) directed against a protein epitope of Echinococcus granulosus antigen 5 was used to screen a cDNA library constructed from E. granulosus protoscoleces RNA. One clone designated Eg14 was selected and shown to code for an amino acid sequence partially homologous to that of the clone Eg6 previously identified with the same MAb. Hydrophobic cluster analysis showed that both recombinant antigens may adopt a similar alpha helical organization and share a common conformational epitope. A synthetic peptide (89-122) mimicking the conformational site of Eg6 and Eg14 was constructed and demonstrated to be able to inhibit binding of the MAb and human hydatid sera to the Eg6 fusion protein (FP6) or to native hydatid antigens. To assess the diagnostic value of the peptide 89-122, we tested sera from patients infected with different parasites for their antibody reactivity with this peptide in ELISA. A high binding sensitivity and specificity of IgG-A-M antibodies were obtained with E. granulosus-infected patient sera. Moreover, the peptide 89-122 was found to be specifically recognized by IgE antibodies from patients with hydatid disease. These results indicate the particular interest of this synthetic peptide as a standardized antigen in diagnosis and treatment surveillance of hydatidosis. PMID- 1737837 TI - Molecular basis of lactase levels in adult humans. AB - The molecular basis of adult human "lactase deficiency" has long been a subject of controversy. To address this issue, small intestinal biopsies from orienta, black, and white patients were analyzed. Adjacent samples were assayed for lactase and sucrase specific activities and the sucrase/lactase ratio (high ratio signifies lactase deficiency), and the results were compared to lactase steady state mRNA levels detected in Northern blots probed with a human lactase mDNA. All oriental patients had high ratios and no detectable lactase mRNA. Four black patients had a similar pattern; two with low ratios had detectable mRNA. The group of white patients displayed a range of findings, from high ratio/no mRNA to low ratio/considerable mRNA. Elevated levels of lactase mRNA always correlated with the presence of elevated levels of lactase enzyme activity, suggesting that the difference in levels of adult human intestinal lactase activity among racial groups may be regulated at the level of gene transcription. PMID- 1737838 TI - Fibroblasts modulate intestinal secretory responses to inflammatory mediators. AB - Cultured colonic epithelial cells and fibroblasts were used to examine the interaction between these cell types during intestinal secretion. Secretory responses of T84 colonic epithelial cells, measured as changes in the short circuit current in modified Ussing chambers to bradykinin, serotonin, hydrogen peroxide, and histamine, were enhanced in the presence of fibroblasts, either in cocultures or when separate cultures of fibroblasts were acutely juxtaposed with the T84 cultures. This effect was abolished by pretreatment with indomethacin and the fibroblasts were found to release prostaglandin E2 in response to these inflammatory mediators. Fibroblasts may exert a paracrine regulation on the secretory response of intestinal epithelial cells via the generation and release of cyclooxygenase products in response to inflammatory mediators. These studies suggest a novel function for the intestinal fibroblastic sheath: that of amplification of the inflammatory response through mesenchymal/epithelial interaction. PMID- 1737839 TI - Exacerbation of ischemic dysfunction by angiotensin II in red cell-perfused rabbit hearts. Effects on coronary flow, contractility, and high-energy phosphate metabolism. AB - We studied the effects of angiotensin II during low-flow ischemia and reperfusion using red cell-perfused isovolumic rabbit hearts. Under baseline conditions where coronary perfusion pressure (CPP) was 100 mm Hg and left ventricular end diastolic pressure (LVEDP) was set at 10 mm Hg, 10(-8) M angiotensin II caused a mild increase in LV developed pressure (+12%) and decrease in coronary flow ( 8%). Low-flow ischemia was imposed by reducing CPP to 15 mm Hg for 30 min followed by 30 min of reperfusion. During ischemia, the angiotensin II group showed a gradual further reduction in coronary flow in association with a greater depression of LV developed pressure and increase in LVEDP relative to the no-drug group. To separate the effect of angiotensin II on coronary flow from a direct myocardial effect, the angiotensin II group was compared with an additional no drug group with a matched progressive reduction in coronary flow during ischemia. In these groups, the ischemic depression of LV developed pressure, myocardial ATP levels, and lactate production were similar. However, the ischemic rise in LVEDP was greater (42.0 +/- 5.4 vs. 19.9 +/- 1.3 mm Hg, P less than 0.01) and recovery was incomplete in the angiotensin II group. These observations suggest that angiotensin II exerts a direct adverse effect on LV diastolic relaxation during low-flow ischemia and recovery. PMID- 1737840 TI - Two different allelic mutations in the lecithin-cholesterol acyltransferase gene associated with the fish eye syndrome. Lecithin-cholesterol acyltransferase (Thr123----Ile) and lecithin-cholesterol acyltransferase (Thr347----Met). AB - We have elucidated the genetic defect in a 66-yr-old patient with fish eye syndrome (FES) presenting with severe corneal opacities and hypoalphalipoproteinemia. The patient's plasma concentration of high density lipoprotein (HDL) cholesterol was reduced at 7.7 mg/dl (35.1-65.3 mg/dl in controls) and the HDL cholesteryl ester content was 31% (60-80% in controls); however, total plasma cholesteryl esters were similar to normal (60% of total cholesterol vs. a mean of 66% in controls). The patient's plasma cholesterol esterification rate was slightly reduced at 51 nmol/ml per h (control subjects: 61-106 nmol/ml per h), whereas lecithin-cholesterol acyltransferase (LCAT) activity, assayed using a HDL-like exogenous proteoliposome substrate, was virtually absent (0.9 nmol/ml per h vs. 25.1-27.9 nmol/ml per h in control subjects). DNA sequence analysis of the proband's LCAT gene revealed two separate C to T transitions resulting in the substitution of Thr123 with Ile and Thr347 with Met. The mutation at codon 347 created a new restriction site for the enzyme Nla III. Analysis of the patient's polymerase chain reaction-amplified DNA containing the region of the Thr347 mutation by digestion with Nla III confirmed that the proband is a compound heterozygote for both defects. The patient's daughter, who is asymptomatic despite a 50% reduction of LCAT activity, is heterozygous for the Thr123----Ile mutation. Our data indicate that the regions adjacent to Thr123 and Thr347 of LCAT may play an important role in HDL cholesterol esterification, suggesting that these regions may contain a portion of the LCAT binding domain(s) for HDL. PMID- 1737841 TI - Prevention of diabetes in BB/Wor rats by intrathymic islet injection. AB - The objective of this study was to determine whether the intrathymic injection of islets can prevent the development of diabetes in BB/Wor rats. Evidence suggests that a failure to induce islet thymic tolerance may be an etiological factor in the development of the disease. It was theorized that the introduction of islets into the thymus might directly induce islet tolerance and thus prevent disease. Islets from diabetes-resistant BB/Wor rats were injected into the thymuses of 23 young diabetes-prone BB/Wor rats; 25 sham-operated animals served as controls. Results showed that 22 of the 25 control rats became diabetic while only 8 of the 23 experimental rats became diabetic (P less than 0.0002). The specific lysis of islet cells by spleen cells from nondiabetic experimental and control rats was comparable and less than the lysis induced by spleen cells from diabetic rats. These data demonstrate that the intrathymic injection of islets into diabetes prone BB/Wor rats is an effective method for preventing the development of autoimmune type I diabetes. PMID- 1737842 TI - Tubular antigen-binding proteins repress transcription of type IV collagen in the autoimmune target epithelium of experimental interstitial nephritis. AB - We have been studying immune interactions with somatic cells using a tubular antigen-binding protein (ThF) secreted by helper T lymphocytes harvested from mice that have an autoimmune form of interstitial nephritis called anti-tubular basement membrane disease. This ThF, although characterized originally because of its ability to induce effector T cells, additionally recognizes the nephritogenic 3M-1 antigen expressed by its target renal tubular epithelium. We believe these proteins, in general, may modulate directly some homeostatic functions in organ derived cells, and now report that our ThF represses specifically the cellular transcription and secretion of basement membrane type IV collagen in tubular epithelium. These in vitro findings of reduced levels of mRNA encoding type IV collagen correlate well with in situ hybridization studies performed on kidneys expressing early autoimmune lesions, and predict a progressive drop in the expression of type IV collagen in the interstitium. Such a novel and unexpected repression of transcription of type IV collagen might easily impart or facilitate permanent change in the infrastructure of kidney architecture during autoimmune injury and, perhaps, contributes to the process of tubular atrophy attendant to prolonged renal inflammation. PMID- 1737843 TI - Regulation of intestinal lactase in adult hypolactasia. AB - Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine. PMID- 1737844 TI - Calcium and potassium are important regulators of barrier homeostasis in murine epidermis. AB - Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluoroperazine or N-6-aminohexyl-5-chloro-1 naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions. PMID- 1737845 TI - Thromboerythrocytes. In vitro studies of a potential autologous, semi-artificial alternative to platelet transfusions. AB - In an attempt to overcome the limitations and drawbacks of using fresh platelets for transfusion therapy of thrombocytopenic patients, we have performed in vitro experiments on an autologous, semi-artificial alternative to platelet transfusions. Based on our previous studies of the interactions of unactivated and activated platelets with beads coated with peptides of various lengths, all of which contained the arginine-glycine-aspartic acid (RGD) cell recognition sequence, the peptide Ac-CGGRGDF-NH2 was chosen for covalent coupling to erythrocytes. A heterobifunctional crosslinking reagent (N-maleimido-6 aminocaproyl ester of 1-hydroxy-2-nitrobenzene-4-sulfonic acid) was used to crosslink via the peptide's free sulfhydryl group and the erythrocyte's surface amino groups. Approximately 0.5-1.5 x 10(6) peptide molecules bound per erythrocyte after 2 h of incubation, and most of the peptides appeared to crosslink to glycophorin A. The resulting cells, termed thromboerythrocytes, interacted selectively with activated platelets to form mixed aggregates. Studies with fluid phase RGD peptides and monoclonal antibodies indicated that the RGD peptides on the thromboerythrocytes interacted with the GPIIb/IIIa receptors on activated platelets. Thromboerythrocytes could also bind to platelets adherent to collagen. There was minimal erythrocyte hemolysis during the formation of thromboerythrocytes and studies of thromboerythrocyte osmotic fragility and cellular deformability showed no significant changes from control erythrocytes. Whereas there is a 20:1 ratio of erythrocytes to platelets in the circulation of normal individuals, the erythrocytes from as little as 50 ml of blood could be transformed into the equivalent of 2 U of platelets by numbers (equivalent to 18 U of platelets by mass), and reinfused into the same individual within several hours. These data encourage us to proceed to in vivo studies to assess the hemostatic efficacy of thromboerythrocytes in thrombocytopenic animals. PMID- 1737846 TI - Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. AB - Peripheral blood lymphocytes (PBL) were obtained from HIV-1-infected patients at different stages of disease. The absolute number of IgM-, IgG-, and IgA-producing lymphocytes per 10(6) PBL was increased 2.8-, 3.4-, and 1.9-fold, respectively, compared with normal controls. 2-17% of IgG-secreting patient cells reacted with the gp160 envelope glycoprotein of HIV-1 (a 737-fold increase over background), while 1-9% reacted with p24 (140-fold over background). In addition to this HIV specific B cell activation, the number of lymphocytes reactive with nonviral antigens such as DNA, myosin, actin, trinitrophenylated keyhole limpet hemocyanin, and ovalbumin was increased by a mean of 17.9-fold. Evidence suggests that the latter changes reflect an HIV-induced polyclonal B cell activation unrelated to the production of anti-HIV antibodies. For example, the proportion of IgG anti-gp160- and anti-p24-secreting lymphocytes declined in patients with advanced disease, whereas the number of B cells producing antibodies to non-HIV antigens rose. Moreover, CD4 cell count and T4/T8 ratio showed a significant inverse correlation with the degree of polyclonal activation but not with anti HIV responsiveness. These observations demonstrate that both quantitative and qualitative changes in B cell activation accompany (and may be predictive of) disease progression in HIV-infected individuals. PMID- 1737847 TI - An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen. AB - Mutations affecting the pro alpha 1(I) or pro alpha 2(I) collagen genes have been identified in each of the major clinical types of osteogenesis imperfecta. This study reports the presence of a heritable connective tissue disorder in a family with an osteopenic syndrome which has features of mild osteogenesis imperfecta but was considered idiopathic osteoporosis in the proband. At age 38, while still premenopausal, she was found to have osteopenia, short stature, hypermobile joints, mild hyperelastic skin, mild scoliosis, and blue sclerae. There was no history of vertebral or appendicular fracture. Hip and vertebral bone mineral density measurements were consistent with marked fracture risk. Delayed reduction SDS-PAGE of pepsin-digested collagens from dermal fibroblast cultures demonstrated an anomalous band migrating between alpha 1(I) and alpha 1(III). This band merged with the normal alpha-chains upon prereduction, indicating an unexpected cysteine residue. Cyanogen bromide peptide mapping suggested that the mutation was in the smaller NH2-terminal peptides. cDNA was reverse transcribed from mRNA and amplified by the polymerase chain reaction. A basepair mismatch between proband and control alpha 1(I) cDNA hybrids was detected by chemical cleavage with hydroxylamine:piperidine. The cysteine substitution was thus localized to alpha 1(I) exon 9 within the cyanogen bromide 4 peptide. Nucleotide sequence analysis localized a G----T point mutation in the first position of helical codon 43, replacing the expected glycine (GGT) residue with a cysteine (TGT). The prevalence of similar NH2-terminal mutations in subjects with this phenotype which clinically overlaps idiopathic osteoporosis remains to be determined. PMID- 1737848 TI - Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript. AB - We have systematically investigated a genetic defect resulting in a primary lipoprotein lipase (LPL) deficiency in a proband TN and his affected brother SN, both manifesting familial hyperchylomicronemia. Neither LPL activity nor immunoreactive LPL mass was detected in postheparin plasma from the two patients. Immunocytochemical and biosynthetic studies on the proband's monocyte-derived macrophages with rabbit anti-human LPL antiserum revealed that no immunochemically detectable LPL protein was found in either the cells or culture medium, whereas LPL having a molecular mass of 61 kD was detected in normal cells. No detectable LPL mRNA was identified from poly(A)+RNA of the proband's macrophages by Northern blot analysis, and grossly visible LPL gene rearrangement was not observed by Southern blot analysis. Sequence analysis of polymerase chain reaction-amplified LPL gene exons detected one base deletion of G (first position of Ala221) at base 916 in exon 5 which leads to a premature termination by a frameshift. This mutation, designated as LPLArita and resulting in the loss of an AluI restriction enzyme site, was newly identified. We further analyzed the LPL gene from the two patients and their family members by digestion with AluI. Both patients were homozygous for LPLArita allele, while their spouses did not have this mutation. As genetically expected, their children were all heterozygous for LPLArita. We conclude that primary LPL deficiency in the proband was caused by a lack of enzyme synthesis due to the absence of LPL mRNA resulting from one base deletion of G in exon 5, and that heterozygous LPLArita deficient subjects show almost half value of control LPL mass. PMID- 1737849 TI - Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen. AB - To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (alpha 5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to alpha 1 and alpha 5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the alpha 3 chain of type IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen. PMID- 1737850 TI - Defective insulin response of phosphorylase phosphatase in insulin-resistant humans. AB - Insulin-stimulated glycogen synthase activity in human muscle is reduced in insulin-resistant subjects. Insulin regulation of human muscle glycogen synthase may require activation of a type-1 protein phosphatase (PP-1). We investigated the change of phosphorylase phosphatase and glycogen synthase activities in muscle biopsies obtained during a 2-h hyperinsulinemic euglycemic clamp in 12 insulin-sensitive (group S) and 8 insulin-resistant (group R) subjects. Fasting phosphorylase phosphatase activity was lower in group R than in group S, and did not increase significantly with insulin infusion in group R until 20 min. In group S, phosphorylase phosphatase was significantly stimulated by 10 min, remaining significantly higher than in group R at all time points. The insulin mediated changes in phosphatase activities were not decreased by 3 nM okadaic acid but were completely inhibited by 1 microM okadaic acid, thereby verifying that insulin-stimulated phosphorylase phosphatase is accounted for by a PP-1. Subcellular fractionation demonstrated reduced fasting PP-1 activities in both the glycogen and cytosolic fractions of muscle obtained from subjects in group R compared to those in group S. These results suggest that insulin activation of PP 1 could contribute to the stimulation of glycogen synthase by this hormone in human muscle. Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects. PMID- 1737851 TI - Pathobiology of cast nephropathy from human Bence Jones proteins. AB - Renal failure is a common accompaniment of multiple myeloma and is usually due to cast nephropathy, or "myeloma kidney." To understand this lesion, four human Bence Jones proteins (BJP) were purified from the urine of volunteers who had either no evidence of renal dysfunction (BJP1) or renal failure from cast nephropathy (BJP2, BJP3, BJP4). When infused directly into the rat nephron in vivo, BJP2, BJP3, and BJP4 produced intraluminal obstruction by precipitating in the distal nephron; protein casts were never identified before the tip of the loop of Henle. Obstruction was related to the concentration of BJP in the perfusate. Addition of furosemide to the perfusate augmented obstruction in a concentration-dependent fashion. Pretreatment of rats with colchicine completely prevented obstruction and cast formation of perfused nephrons; beta lumicolchicine did not prevent obstruction. Tamm-Horsfall glycoprotein purified from beta-lumicolchicine-treated and untreated rats coaggregated with BJP3 in vitro. Tamm-Horsfall glycoprotein from colchicine-treated rats did not contain sialic acid and did not aggregate with BJP3 in vitro. Thus, cast-forming human BJP coaggregated with Tamm-Horsfall glycoprotein and obstructed the rat distal nephron. Intranephronal obstruction was aggravated by decreasing extracellular fluid volume or adding furosemide. Finally, by decreasing secretion and altering the carbohydrate moiety of Tamm-Horsfall glycoprotein, colchicine prevented intraluminal cast formation and obstruction of the rat nephron. PMID- 1737852 TI - Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. AB - The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia. PMID- 1737853 TI - Binding of nonmucoid Pseudomonas aeruginosa to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis. AB - Lung infections due to Pseudomonas aeruginosa and Pseudomonas cepacia are common in patients with cystic fibrosis. Initial colonization is due to nonmucoid P. aeruginosa, while later mucoid variants emerge and are associated with chronic infection. P. cepacia colonization tends to be more prevalent in older patients. The present study was conducted to discover whether highly purified mucins (from cystic fibrosis sputum and control intestinal secretions) exhibited specific binding of nonmucoid P. aeruginosa. In vitro solid phase microtiter binding assays (with or without a blocking agent) as well as solution phase assays were conducted. Bacteria bound to both mucins via bacterial pili, but no differences in binding capacity were noted between the mucins. Unlike P. cepacia (described in the accompanying manuscript) there was also no preferential binding of P. aeruginosa to mucins versus bovine serum albumin, casein, gelatin, or a host of structurally unrelated proteins and glycoproteins. Carbohydrate hapten inhibition studies did not suggest the existence of specific mucin carbohydrate receptors for P. aeruginosa. In solid phase assays a low concentration (0.05 M) of tetramethylurea abolished P. aeruginosa bacterial binding to both mucins as well as to BSA, whereas in solution phase assays mucin binding to bacteria was not completely disrupted by tetramethylurea. Specific monoclonal antipilus antibodies did not inhibit binding to a greater extent than did Fab fragments of normal mouse IgG. Binding of strains PAO1 and PAK (and isolated PAK pili) to buccal epithelial cells was not influenced by the presence of mucin in binding assay mixtures. Our findings do not support the widely held notion that specific mucin receptors are responsible for the attachment of P. aeruginosa pili, nor do they support the idea that there is a competitive interference by mucins of bacterial binding to respiratory cells. In patients with cystic fibrosis, it would seem unlikely therefore that initial colonization of the lungs by P. aeruginosa is due to a 'selective tropism' of these bacteria for respiratory mucin. PMID- 1737854 TI - Recovery of energy metabolism in rat brain after carbon monoxide hypoxia. AB - Carbon monoxide (CO) may inhibit mitochondrial electron transport in the brain and increase the toxic effects of the gas. This hypothesis was investigated in anesthetized rats during CO exposure and recovery at either normobaric or hyperbaric O2 concentrations. During exposure and recovery, we measured the oxidation level of cerebrocortical cytochrome c oxidase by differential spectroscopy and biochemical metabolites known to reflect aerobic energy provision in the brain. CO exposure (HbCO = 71 +/- 1%) significantly decreased blood pressure and cytochrome oxidation level. Cerebral ATP was maintained while lactate/pyruvate, glucose, and succinate rose, and phosphocreatine (PCr) fell, relative to control (P less than 0.05). Intracellular pH (pHi) calculated from the PCr equilibrium also declined during the exposures. During recovery, HbCO fell more rapidly at hyperbaric than at normobaric O2 levels, but returned to 10% or less in both groups by 45 min. Cytochrome oxidation state improved to 80% of control after 90 min at normobaric O2, but recovered completely after hyperbaric O2 (P less than 0.05). In normobaric O2, PCr and pHi continued to fall for 45 min after CO exposure and did not recover completely by 90 min. PCr and pHi in animals after hyperbaric O2 improved within 45 min, but also remained below control at 90 min. These data indicate that intracellular uptake of CO can impair cerebral energy metabolism, despite the elimination of HbCO from the blood. PMID- 1737855 TI - Molecular basis for membrane rigidity of hereditary ovalocytosis. A novel mechanism involving the cytoplasmic domain of band 3. AB - Hereditary ovalocytic red cells are characterized by a marked increase in membrane rigidity and resistance to invasion by malarial parasites. The underlying molecular defect in ovalocytes remained a mystery until Liu and colleagues (N. Engl. J. Med. 1990. 323:1530-38) made the surprising observation that the ovalocytic phenotype was linked to a structural polymorphism in band 3, the anion transporter. We have now defined the mutation in band 3 gene and established the biophysical sequelae of this mutation. This mutation involves the deletion of amino-acids 400-408 in the boundary between the cytoplasmic and the first transmembrane domains of band 3. The biophysical consequences of this mutation are a marked decrease in lateral mobility of band 3 and an increase in membrane rigidity. Based on these findings, we propose the following model for increased membrane rigidity. The mutation induces a conformational change in the cytoplasmic domain of band 3, leading to its entanglement in the skeletal protein network. This entanglement inhibits the normal unwinding and stretching of the spectrin tetramers necessary for membrane extension, leading to increased rigidity. These findings imply that the cytoplasmic domain of an integral membrane protein can have profound effects on membrane material behavior. PMID- 1737856 TI - Congenital erythropoietic porphyria: identification and expression of exonic mutations in the uroporphyrinogen III synthase gene. AB - Congenital erythropoietic porphyria (CEP), an inborn error of heme biosynthesis, results from the deficient activity of uroporphyrinogen III synthase (URO synthase). This autosomal recessive disorder is heterogeneous; patients with severe disease are often transfusion dependent, while milder patients primarily have cutaneous involvement. To investigate this phenotypic heterogeneity, exonic point mutations in the URO-synthase gene were identified in unrelated CEP patients. Four missense mutations were identified: (a) an A to G transition of nucleotide (nt) 184 that predicted a Thr to Ala substitution at residue 62 (designated T62A); (b) a C to T transition of nt 197 that encoded an Ala to Val replacement at residue 66 (A66V); (c) a T to C transition of nt 217 that predicted a Cys to Arg substitution at residue 73 (C73R); and (d) a C to T transition of nt 683 that resulted in a Thr to Met replacement at residue 228 (T228M). In addition, a G to A transition of nt 27 that did not change the encoded amino acid (A9A) was detected in an African patient. The T62A, C73R, and T228M alleles did not express detectable enzymatic activity, while the A66V allele expressed residual, but unstable activity. The C73R allele was present in eight of 21 unrelated CEP patients (21% of CEP alleles). In three patients, identification of both alleles permitted genotype-phenotype correlations; the A66V/C73R, T228M/C73R, and C73R/C73R genotypes had mild, moderately severe, and severe disease, respectively. These findings provide the first genotype-phenotype correlations and permit molecular heterozygote detection in this inherited porphyria. PMID- 1737857 TI - Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4. AB - A major defect contributing to impaired insulin action in human obesity is reduced glucose transport activity in skeletal muscle. This study was designed to determine whether the improvement in whole body glucose disposal associated with weight reduction is related to a change in skeletal muscle glucose transport activity and levels of the glucose transporter protein GLUT4. Seven morbidly obese (body mass index = 45.8 +/- 2.5, mean +/- SE) patients, including four with non-insulin-dependent diabetes mellitus (NIDDM), underwent gastric bypass surgery for treatment of their obesity. In vivo glucose disposal during a euglycemic clamp at an insulin infusion rate of 40 mU/m2 per min was reduced to 27% of nonobese controls (P less than 0.01) and improved to 78% of normal after weight loss of 43.1 +/- 3.1 kg (P less than 0.01). Maximal insulin-stimulated glucose transport activity in incubated muscle fibers was reduced by approximately 50% in obese patients at the time of gastric bypass surgery but increased twofold (P less than 0.01) to 88% of normal in five separate patients after similar weight reduction. Muscle biopsies obtained from vastus lateralis before and after weight loss revealed no significant change in levels of GLUT4 glucose transporter protein. These data demonstrate conclusively that insulin resistance in skeletal muscle of mobidly obese patients with and without NIDDM cannot be causally related to the cellular content of GLUT4 protein. The results further suggest that morbid obesity contributes to whole body insulin resistance through a reversible defect in skeletal muscle glucose transport activity. The mechanism for this improvement may involve enhanced transporter translocation and/or activation. PMID- 1737858 TI - Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. AB - Apo E plays an important role in plasma lipoprotein metabolism through its high affinity binding to cell surface LDL receptor. In the present study, we studied the effects of apo E on the atherogenic process in Watanabe heritable hyperlipidemic rabbits which are deficient in LDL receptor and an animal model for familial hypercholesterolemia. We isolated apo E from plasma of 1% cholesterol-fed rabbits and administered 10 mg of purified apo E intravenously into five Watanabe heritable hyperlipidemic rabbits three times a week from their age of 2.5 months to 11 months for 8.5 months. After sustained administration to apo E, we found a significant reduction in the accumulation of cholesterol ester in aortae (1.55 +/- 0.07 mg/g tissue) as compared to control rabbits (4.32 +/- 0.61 mg/g tissue). Supporting this, the percentage of the surface area of the aorta with macroscopic plaque was remarkably decreased in apo E-treated animals (18.8 +/- 5.1% vs. 38.8 +/- 8.0% in control). Thus, apo E definitely prevented the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. PMID- 1737860 TI - Retraction. PMID- 1737859 TI - Are cysteine-rich and COOH-terminal domains of dystrophin critical for sarcolemmal localization? AB - It has been hypothesized that the tight localization of dystrophin at the muscle membrane is carried out by its cysteine-rich and/or carboxyl domains. We report the results of biochemical and immunocytochemical investigations of dystrophin in muscle from a 1-yr-old patient with a large deletion that removes the distal part of the dystrophin gene, thus spanning the exons coding for the cysteine-rich and the carboxy-terminal domains, and extends beyond the glycerol kinase and congenital adrenal hypoplasia genes. Immunological analysis of muscle dystrophin shows that the deletion results in the production of a truncated, but stable, polypeptide correctly localized at the sarcolemma. These data indicate that neither the cysteine-rich domain, nor the carboxyl domain, are necessary for the appearance of normal dystrophin sarcolemmal localization. PMID- 1737861 TI - Are we creating socially responsible dental professionals? PMID- 1737862 TI - Instructional and information technology initiatives: the potential for delivery. AB - An attempt has been made to discuss some of the issues and opportunities which lie ahead as dental educators, their institutions, and our national associations prepare for the expected growth in the instructional and informational technologies that curriculum reform and technological advances will promote. The issues stem from a perceived need to collectively deliver products, as well as discuss issues, within our associations. While most national professional associations are well equipped to focus on questions of policy rather than the production of specific products, I believe there is a real potential for the successful pursuit of both within dental education. PMID- 1737863 TI - Using patient-instructors to teach and evaluate interviewing skills. AB - The teaching and evaluation of clinical interviewing skills is a continuing challenge for medicine and dentistry. The use of patient-instructors who provide consistency in presenting scenarios has recently been pioneered in dental education. This program focused primarily on teaching and used patient instructors to give individual feedback from the patient's perspective to students after each of five scenarios. Feedback was constructive and behaviorally oriented so that it could be applied immediately to succeeding scenarios. Rating instruments assessed both process and content skills. Results indicated that students improved significantly in interpersonal interviewing skills as they progressed through the exercise. Content skills improved only slightly. Student and faculty reaction was positive. The program is an effective and time efficient means of teaching history taking and interviewing skills as well as an effective evaluation tool. PMID- 1737864 TI - A survey of instructional technology in dental education. AB - Little is known about current use of hardware and non-hardware instructional technologies in dental education. To address this area, the investigators designed a questionnaire to assess support for the development of instructional technology and determine the extent to which different instructional technologies are used in North American dental schools. Responses were received from 59 of 65 dental schools (91 percent). Respondents at most schools judged the administration at their school to be supportive of the development of instructional technology, but in general, did not feel faculty were enthusiastic about or rewarded for developing innovative methods. The most common computer based application involves testing and record keeping, which is used extensively in about half the dental schools. Individualized instruction and paper and pencil simulations are used in at least some courses at a majority of dental schools. Schools with available support services apply certain technologies to a significantly greater extent than schools without available support services. PMID- 1737865 TI - Attitudes of dental hygiene students toward individuals with AIDS. PMID- 1737866 TI - Current teaching of proximal retention grooves for Class II amalgam preparations. PMID- 1737867 TI - A dental school sponsored, pre-paid dental plan for college students. PMID- 1737868 TI - Implementation of a team concept of patient care. PMID- 1737869 TI - The willed future: thoughts garnered from the Cheshire cat. PMID- 1737870 TI - The effect of postdoctoral general dentistry programs on specialization. PMID- 1737871 TI - Hearing protection against high-level shooting impulses in relation to hearing damage risk criteria. AB - The earmuff attenuation of acoustic impulses produced by large-caliber weapons was measured with a high-speed microcomputer controlled unit. The estimated accuracy was +/- 1 dB in peak sound-pressure level measurements. The peak levels outside earmuffs were 184 dB for the heavy bazooka and 172 dB for the hand-held bazooka (re: 20 microPa). Heavy bazooka impulse peak levels were attenuated from 7 to 19 dB by the earmuffs depending on the mass and volume of the measured three types of earmuffs. Hand-held bazooka impulse peak levels were attenuated by the earmuffs from 9 to 15 dB. The risk limits for hearing loss from a single impulse were exceeded in spite of the use of earmuffs when the criteria of CHABA (USA) or Pfander (Germany) were applied. The unexpectedly low attenuation was due to the low-frequency waveform of the high-level impulses. The earmuffs were found to prolong the impulse duration, which may reduce the benefit otherwise achieved by attenuation of the peak levels. PMID- 1737872 TI - Short-term poststimulatory response characteristics of the human acoustic stapedius reflex: monotic and dichotic stimulation. AB - Two experiments were performed to study short-term poststimulatory response characteristics of the human acoustic stapedius reflex in the time and intensity domains. In experiment 1, monotic magnitude-intensity functions (MIFs) were obtained for a 20-ms test stimulus preceded by a conditioning stimulus varying in duration (20, 50, 100, 500 ms) and level (-10, 0, +10 dB re: stapedius-reflex threshold) and temporally separated from the test stimulus by various interstimulus intervals (ISIs) (0, 20, 50, 100, 500 ms). Experiment 2 was similar in design except that conditioner and test stimuli were presented dichotically and fewer ISIs were used. Both experiments demonstrated that a prior conditioning stimulus produced significant increases in test-stimulus response magnitude. These poststimulatory effects were characterized by complex interactions among stimulus variables (conditioner duration, conditioner level, and interstimulus interval) with similar interactions occurring for both monotic and dichotic stimuli. A simple superposition effect of the responses to the conditioner and test stimulus does not account for the effect of prior stimulation since responses often exceeded the sum of the responses to the conditioner and the test stimulus alone. PMID- 1737873 TI - Responses to amplitude-modulated tones in the auditory nerve of the cat. AB - Sinusoidally amplitude-modulated (AM) tones are frequently used in psychophysical and physiological studies, yet a comprehensive study on the coding of AM tones in the auditory nerve is lacking. AM responses of single auditory-nerve fibers of the cat are studied, systematically varying modulation depth, frequency, and sound level. Synchrony-level functions were nonmonotonic with maximum values that were inversely correlated with spontaneous rate (SR). In most fibers, envelope phase-locking showed a positive gain. Modulation transfer functions were uniformly low pass. Their corner frequency increased with characteristic frequency (CF), but changed little for CFs above 10 kHz. The highest modulation frequencies to which phase locking occurred were more than 0.8 oct lower than the highest frequencies to which phase locking to pure tones occurs. Cumulative, or unwrapped, phase increased linearly with modulation frequency: The slope was inversely related to CF, and slightly higher than group delays reported for pure tones. High SR, low CF fibers showed the poorest envelope phase locking. In some low CF fibers, phase locking increased at high levels, associated with "peak splitting" phenomena. Changes in average rate due to modulation were small, and could be enhancement or suppression. PMID- 1737874 TI - Modeling the identification of concurrent vowels with different fundamental frequencies. AB - Human listeners are better able to identify two simultaneous vowels if the fundamental frequencies of the vowels are different. A computational model is presented which, for the first time, is able to simulate this phenomenon at least qualitatively. The first stage of the model is based upon a bank of bandpass filters and inner hair-cell simulators that simulate approximately the most relevant characteristics of the human auditory periphery. The output of each filter/hair-cell channel is then autocorrelated to extract pitch and timbre information. The pooled autocorrelation function (ACF) based on all channels is used to derive a pitch estimate for one of the component vowels from a signal composed of two vowels. Individual channel ACFs showing a pitch peak at this value are combined and used to identify the first vowel using a template matching procedure. The ACFs in the remaining channels are then combined and used to identify the second vowel. Model recognition performance shows a rapid improvement in correct vowel identification as the difference between the fundamental frequencies of two simultaneous vowels increases from zero to one semitone in a manner closely resembling human performance. As this difference increases up to four semitones, performance improves further only slowly, if at all. PMID- 1737875 TI - Intensity and frequency resolution: masking of absolute identification and fixed and roving discrimination. AB - Auditory intensity and frequency resolution were studied in three paradigms under masking conditions. Absolute identifications of single stimuli (one-interval paradigm) and 2IFC judgments of fixed- and roving-level pairs of stimuli (two interval paradigm) were obtained from the same experienced observers. Judgments were made under optimal (no mask) conditions, in the presence of a broadband noise mask (simultaneous mask), and when the stimulus(i) to be judged were either preceded (forward mask) or followed (backward mask) by a broadband noise mask. Substantial masking of intensity resolution was found in all mask conditions. Only a simultaneous mask affected frequency resolution. In the no mask condition, performance was best for fixed-level (or frequency) 2IFC discrimination, followed by roving-level (frequency) 2IFC, and finally absolute identification. These differences were maintained under masking for frequency resolution, but not for intensity resolution. The results are discussed in terms of the Braida and Durlach (1988) model of intensity resolution. A similar model is suggested for frequency resolution with differences suggested by the differences in neural coding of sound intensity and frequency. PMID- 1737876 TI - Auditory filter shapes at low center frequencies in young and elderly hearing impaired subjects. AB - Auditory filter shapes were measured for two groups of hearing-impaired subjects, young and elderly, matched for audiometric loss, for center frequencies (fc) of 100, 200, 400, and 800 Hz using a modified notched-noise method [B. R. Glasberg and B. C. J. Moore, Hear. Res. 47, 103-138 (1990)]. Two noise bands, each 0.4fc wide, were used; they were placed both symmetrically and asymmetrically about the signal frequency to allow the measurement of filter asymmetry. The overall noise level was either 77 or 87 dB SPL. Stimuli were delivered monaurally using Sennheiser HD424 earphones. Although auditory filters for the hearing-impaired subjects were generally broader than for normally hearing subjects [Moore et al., J. Acoust. Soc. Am. 87, 132-140 (1990)], some hearing-impaired subjects with mild losses had normal filters. The filters tended to broaden with increasing hearing loss. There were not any clear differences in filter characteristics between young and elderly hearing-impaired subjects. The signal-to-noise ratios at the outputs of the auditory filters required for threshold (K) tended to be lower than normal for the young hearing-impaired subjects, but were not significantly different from normal for the elderly hearing-impaired subjects. The lower K values for the young hearing-impaired subjects may occur because broadened auditory filters reduce the deleterious effects on signal detection of fluctuations in the noise. PMID- 1737877 TI - Signal detection in temporally modulated and spectrally shaped maskers. AB - The first part of this paper presents several experiments on signal detection in temporally modulated noise, yielding a general approach toward the concept of comodulation masking release (CMR). Measurements were made on masked thresholds of both long- and short-duration, narrow-band signals presented in a 100% sinusoidally amplitude-modulated (SAM) noise masker (modulation frequency 32 Hz), as a function of masker bandwidth from 1/3 oct up to 13/3 octs, while the masker band was geometrically centered at signal frequency. With the short-duration signals placed in the valley of the masker, a substantial CMR (i.e., a decrease of masked threshold with increasing masker bandwidth) was found, whereas for the long-duration signals CMR was smaller. Furthermore, investigations were carried out to determine whether CMR changes when the bandwidth of the signals, consisting of bandpass impulse responses, is increased. The data indicate that substantial CMR remains even when all masker bands contain a signal component, thus minimizing across-channel differences. This finding is not in line with current models accounting for the CMR phenomenon. The second part of this paper concerns signal detection in spectrally shaped noise. Also investigated was whether release from masking occurs for the detection of a pure-tone signal at a valley or a peak of a simultaneously presented masking noise with a sinusoidally rippled power spectrum, when this masker was preceded and followed by a second noise (temporal flanking burst) with an identical spectral shape as the on-signal noise. Similar to CMR effects for temporal modulations, the data indicate that coshaping masking release (CSMR) occurs when the signal is placed in a valley of the spectral envelope of the masker, whereas no release from masking is found when the signal is placed at a peak of the spectral envelope of the masker. The implications of these experiments for measures of spectral and temporal resolution are discussed. PMID- 1737878 TI - The role of frequency selectivity in measures of auditory and vibrotactile temporal resolution. AB - The purpose of this study was to compare the role of frequency selectivity in measures of auditory and vibrotactile temporal resolution. In the first experiment, temporal modulation transfer functions for a sinusoidally amplitude modulated (SAM) 250-Hz carrier revealed auditory modulation thresholds significantly lower than corresponding vibrotactile modulation thresholds at SAM frequencies greater than or equal to 100 Hz. In the second experiment, auditory and vibrotactile gap detection thresholds were measured by presenting silent gaps bounded by markers of the same or different frequency. The marker frequency F1 = 250 Hz preceded the silent gap and marker frequencies after the silent gap included F2 = 250, 255, 263, 310, and 325 Hz. Auditory gap detection thresholds were lower than corresponding vibrotactile thresholds for F2 markers less than or equal to 263 Hz, but were greater than the corresponding vibrotactile gap detection thresholds for F2 markers greater than or equal to 310 Hz. When the auditory gap detection thresholds were transformed into filter attenuation values, the results were modeled well by a constant-percentage (10%) bandwidth filter centered on F1. The vibrotactile gap detection thresholds, however, were independent of marker frequency separation. In a third experiment, auditory and vibrotactile rate difference limens (RDLs) were measured for a 250-Hz carrier at SAM rates less than or equal to 100 Hz. Auditory RDLs were lower than corresponding vibrotactile RDLs for standard rates greater than 10 Hz. Combination tones may have confounded auditory performance for standard rates of 80 and 100 Hz. The results from these experiments revealed that frequency selectivity influences auditory measures of temporal resolution, but there was no evidence of frequency selectivity affecting vibrotactile temporal resolution. PMID- 1737879 TI - Discrimination of interaural envelope correlation and its relation to binaural unmasking at high frequencies. AB - Listeners' sensitivity to interaural correlation of the envelope of high frequency waveforms and whether such sensitivity might account for detectability in a masking-level difference paradigm were assessed. Thresholds of interaural envelope decorrelation (from a reference correlation of 1.0) were measured for bands of noise centered at 4 kHz and bandwidths ranging from 50-1600 Hz. Decorrelation of the envelope was achieved by "mixing" two independent narrow band noises. Separately, with the same listeners, NoSo and NoS pi detection thresholds were measured for maskers of the same center frequency and bandwidths. For bandwidths of noise up to about 400 Hz, listeners were similarly sensitive to interaural decorrelation in both types of task. However, for bandwidths greater than 400 Hz or so, while sensitivity in the discrimination task was unaffected, sensitivity was reduced in the NoS pi conditions. Additional data suggested that listeners were able to maintain their sensitivity independent of bandwidth in the discrimination task by focusing on binaural information within select spectral regions of the stimuli. PMID- 1737880 TI - Spectral integration of broadband signals in diotic and dichotic masking experiments. AB - The method of Gassler [Acustica 4, 408-414 (1954)] was used to measure the audibility of multicomponent signals as a function of their bandwidth against a broadband, white-noise masker. Test signals were composed of 1 to 41 sinusoids with a spectral spacing of 10 Hz and were always spectrally centered around 400 Hz. Masker duration was 400 ms and the 300-ms signals were centered within the noise intervals. A three-interval forced-choice procedure with adaptive level adjustment was applied. NoSo, NoSm, NoS pi, and N pi So masked thresholds were obtained for four subjects. A comparison of the diotic and the three dichotic conditions yields no significant difference in the bandwidth dependence and suggests equal integration bandwidths for all conditions. However, the original results of Gassler could not be replicated: Neither were the overall levels of signals with a bandwidth below the critical bandwidth constant nor were the results for broadband signals in accordance with a single-band model of detection. The narrow-band data are much better described by calculating the overall signal level at the output of a rounded exponential filter [Patterson et al., J. Acoust. Soc. Am. 72, 1788-1803 (1982)] with an equivalent rectangular bandwidth of 65 Hz. For broader signal bandwidths, the signal level at threshold increases as predicted by a multiband model. PMID- 1737881 TI - Effects of temporal separation and masker level on binaural analysis in forward masking. AB - In the present study detection under diotic (NoSo) and dichotic (NoS pi) listening conditions in a forward masking paradigm was investigated. Both the level of a noise masker and the temporal separation between the masker and a 250 Hz tone burst served as independent variables. Results showed that most of the variance in the data could be accounted for by the amount of masking in the NoSo condition, independent of the value of the temporal parameter, which itself accounted for only 1.4% of the variance that remained. Once the data were corrected for NoSo masking effectiveness, the MLD was found to decrease by only 1.4 dB as temporal separation increased from 5-100 ms, which is consistent with a very long time constant for the binaural system. Consistent with this finding, it was shown that slope changes of the growth of masking functions, for simultaneous as compared to forward masking, were similar for both the NoSo and NoS pi conditions. PMID- 1737882 TI - Frequency dependence of binaural performance in listeners with impaired binaural hearing. AB - Binaural performance was measured as a function of stimulus frequency for four impaired listeners, each with bilaterally symmetric audiograms. The subjects had various degrees and configurations of audiometric losses: two had high-frequency, sensorineural losses; one had a flat sensorineural loss; and one had multiple sclerosis with normal audiometric thresholds. Just noticeable differences (jnd's) in interaural time, interaural intensity, and interaural correlation as well as detection thresholds for NoSo and NoS pi conditions were obtained for narrow-band noise stimuli at octave frequencies from 250-4000 Hz. Performance of the impaired listeners was generally poorer than that of normal-hearing listeners, although it was comparable to normal in a few instances. The patterns of binaural performance showed no apparent relation to the audiometric patterns; even the two subjects with similar degree and configuration of hearing loss have very different binaural performance, both in the level and frequency dependence of their performance. The frequency dependence of performance on individual tests is irregular enough that one cannot confidently interpolate between octaves. In addition, it appears that no subset of the measurements is adequate to characterize the performance in the rest of the measurements with the exception that, within limits, interaural correlation discrimination and NoS pi detection performance are related. PMID- 1737883 TI - Effects of noise on detection of amplitude increments of sinusoidal vibration of the skin. AB - Vibrotactile thresholds for detecting a 300-Hz signal in the presence of both a 300-Hz sinusoidal pedestal and a background noise were measured as a function of the amplitudes of the pedestal and noise. Threshold increased monotonically as a function of the amplitude of the noise, but was a nonmonotonic function of the amplitude of the sinusoidal pedestal. Negative masking, in which the pedestal facilitated detection of the test stimulus, was observed in the absence of background noise and in the presence of subthreshold background noise when the pedestal was near or below threshold. Negative masking disappeared when the experiment was conducted in the presence of moderately intense to intense background noise. The results are consistent with a peripheral high-energy threshold for taction. PMID- 1737884 TI - Potential benefits of adaptive frequency-gain characteristics for speech reception in noise. AB - Some current single-microphone hearing aids employ techniques for adaptively varying the frequency-gain characteristics in an attempt to improve speech reception in noise. The potential benefit of this strategy depends on the spectral spread of masking and the degree to which it can be reduced by changing the frequency-gain characteristic. In this study these benefits were examined for subjects with normal hearing under static listening conditions. In the unprocessed condition, subjects were presented with nonsense syllables in an octave-band noise centered on 0.5, 1, or 2 kHz. The frequency-gain characteristic was then modified with the goal of reducing the intensity of the frequency region containing the octave-band noise. This processing resulted in increases as large as 60 percentage points in consonant-correct scores with the low- and mid frequency octave noise bands, and a small increase with the high-frequency noise. Masking patterns produced by the octave noises were also measured and were related to the intelligibility results via an analysis based on Articulation Theory. The Articulation Index was also used to compare the effectiveness of three adaptive rules. A simple multiband volume control is expected to provide much of the benefit of more sophisticated systems without the need for separate estimation of input speech and noise spectra. PMID- 1737885 TI - Fundamental frequency declination is not unique to human speech: evidence from nonhuman primates. AB - In human speech, declination of the fundamental frequency (F0) of the voice spans coherent units of an utterance and, therefore, signals where units begin and end. A rapid final fall at the end of an utterance provides a further indication of an utterance's ending. The occurrence of declination is sufficiently widespread across languages that several investigators have suggested it as a language universal. Language universals may be universal because they are part of a species-specific specialization for language or, alternatively, they may constitute conventionalizations of natural dispositions of the vocal tract that may serve a communicative function. Evidence is offered favoring the latter account for declination and the final fall by showing that vocal productions of vervet monkeys (Cercopithecus aethiops) and rhesus macaques (Macaca mulatta) show declination, and vervets show clear evidence of a final fall. Interestingly, the fall in F0 may serve some communicative role in the vocal exchanges of vervets and rhesus, analogous to its signalling function in human language. PMID- 1737886 TI - Talker and listener effects on degree of perceived foreign accent. AB - Four experiments were carried out to examine listener- and talker-related factors that may influence degree of perceived foreign accent. In each, native English listeners rated English sentences for degree of accent. It was found that degree of accent is influenced by range effects. The larger the proportion of native (or near-native) speakers included in a set of sentences being evaluated, the more strongly accented listeners judged sentences spoken by non-native speakers to be. Foreign accent ratings were not stable. Listeners judged a set of non-native produced sentences to be more strongly accented after, as compared to before, they became familiar with those sentences. One talker-related effect noted in the study was the finding that adults' pronunciation of an L2 may improve over time. Late L2 learners who had lived in the United States for an average of 14.3 years received significantly higher scores than late learners who had resided in the United States for 0.7 years. Another talker-related effect pertained to the age of L2 learning (AOL). Native Spanish subjects with an AOL of five to six years were not found to have an accent (i.e., to receive significantly lower scores than native English speakers), whereas native Chinese subjects with an average AOL of 7.6 years did have a measurable accent. The paper concludes with the presentation of several hypotheses concerning the relationship between AOL and degree of foreign accent. PMID- 1737887 TI - On the sufficiency of compound target specification of isolated vowels and vowels in /bVb/ syllables. AB - It has been suggested [e.g., Strange et al., J. Acoust. Soc. Am. 74, 695-705 (1983); Verbrugge and Rakerd, Language Speech 29, 39-57 (1986)] that the temporal margins of vowels in consonantal contexts, consisting mainly of the rapid CV and VC transitions of CVC's, contain dynamic cues to vowel identity that are not available in isolated vowels and that may be perceptually superior in some circumstances to cues which are inherent to the vowels proper. However, this study shows that vowel-inherent formant targets and cues to vowel-inherent spectral change (measured from nucleus to offglide sections of the vowel itself) persist in the margins of /bVb/ syllables, confirming a hypothesis of Nearey and Assmann [J. Acoust. Soc. Am. 80, 1297-1308 (1986)]. Experiments were conducted to test whether listeners might be using such vowel-inherent, rather than coarticulatory information to identify the vowels. In the first experiment, perceptual tests using "hybrid silent center" syllables (i.e., syllables which contain only brief initial and final portions of the original syllable, and in which speaker identity changes from the initial to the final portion) show that listeners' error rates and confusion matrices for vowels in /bVb/ syllables are very similar to those for isolated vowels. These results suggest that listeners are using essentially the same type of information in essentially the same way to identify both kinds of stimuli. Statistical pattern recognition models confirm the relative robustness of nucleus and vocalic offglide cues and can predict reasonably well listeners' error patterns in all experimental conditions, though performance for /bVb/ syllables is somewhat worse than for isolated vowels. The second experiment involves the use of simplified synthetic stimuli, lacking consonantal transitions, which are shown to provide information that is nearly equivalent phonetically to that of the natural silent center /bVb/ syllables (from which the target measurements were extracted). Although no conclusions are drawn about other contexts, for speakers of Western Canadian English coarticulatory cues appear to play at best a minor role in the perception of vowels in /bVb/ context, while vowel-inherent factors dominate listeners' perception. PMID- 1737888 TI - The effect of accentuation and word duration on the naturalness of speech. AB - In this study the effect of appropriate word duration and correct (pitch) accentuation on the naturalness of speech was investigated. In the stimulus material, the information value of the target word determined the correctness of accentuation ([new, +accent] and [old, -accent] were defined as correct). Appropriate word duration was defined as either "in agreement with accentuation" ([long, +accent] and [short, -accent]) or "in agreement with information value" ([long, new] and [short, old]). Listeners were asked to give naturalness judgments along a scale from 1 (very unnatural) to 10 (very natural) on fragments consisting of two sentences. Duration and accentuation of the target word, which always occurred in the second sentence, were manipulated separately and in combinations. Judgments show that accentuation that is not in agreement with information value causes a significant decrease of naturalness. When accentuation is in agreement with information value but duration is inappropriate for both factors, the perceived naturalness decreases significantly. However, listeners were unable to give consistent naturalness judgments on the manipulated word durations in fragments with incorrect accent distributions. Based on these results and the findings of an earlier production study [W. Eefting, J. Acoust. Soc. Am. 89, 412-424 (1991)], which showed that duration is not involved in the realization of pitch accent, the following is suggested. Speakers adapt both accentuation and word duration in order to indicate that a word contains relevant information. Presence of an accent distinguishes the word from its (less relevant) environment. A longer duration provides the listener with the extra time that is needed in order to process the word's content adequately. PMID- 1737889 TI - Speech reception in quiet and in noisy conditions by individuals with noise induced hearing loss in relation to their tone audiogram. AB - Tone thresholds and speech-reception thresholds were measured in 200 individuals (400 ears) with noise-induced hearing loss. The speech-reception thresholds were measured in a quiet condition and in noise with a speech spectrum at levels of 35, 50, 65, and 80 dBA. The tone audiograms could be described by three principal components: hearing loss in the regions above 3 kHz, from 1 to 3 kHz and below 1 kHz; the speech thresholds could be described by two components: speech reception in quiet and speech reception in noise at 50-80 dBA. Hearing loss above 1 kHz was related to speech reception in noise; hearing loss at and below 1 kHz to speech reception in quiet. The correlation between the speech thresholds in quiet and in noise was only R = 0.45. An adequate predictor of the speech threshold in noise, the primary factor in the hearing handicap, was the pure-tone average at 2 and 4 kHz (PTA2,4, R = 0.72). The minimum value of the prediction error for any tone audiometric predictor of this speech threshold was 1.2 dB (standard deviation). The prediction could not be improved by taking into account the critical ratio for low-frequency noise nor by its upward spread of masking. The prediction error is due to measurement error and to a factor common to both ears. The latter factor is ascribed to cognitive skill in speech reception. Hearing loss above 10 to 15 dB HL (hearing level) already shows an effect on the speech threshold in noise, a noticeable handicap is found at PTA2,4 = 30 dB HL. PMID- 1737890 TI - Method to measure acoustic impedance and reflection coefficient. AB - A frequency-domain based system for measuring acoustic impedance and reflection coefficient is described. The calibration procedure uses a least-mean-squares approximation to the Thevenin parameters describing the source and receiver characteristics in which the data measured on closed, cylindrical tubes are matched to a viscothermal tube model. The system is intended for use in acoustical measurement in human ear canals, in which the cross-sectional area of the ear canal at the point of insertion is imprecisely known. This area is acoustically estimated from the impedance data, and the reflection coefficient is calculated in terms of this area and the impedance data. Measurements on a variety of closed tubes show the method is accurate over the frequency range investigated (less than 10.7 kHz). The time-domain reflection function is evaluated by transforming the reflection coefficient from the frequency domain, but the finite bandwidth of the measured data limits the accuracy of time-domain response measurements. The method is well suited for frequency-domain measurements in human ear canals. PMID- 1737891 TI - Relative ear advantage and element duration. AB - Lauter [J. Acoust. Soc. Am. 71, 701-707 (1982)] reported that although the magnitude and direction of the absolute ear advantage for speech and nonspeech sound sets presented dichotically varies considerably among listeners, consistent patterns of a relative ear advantage (EArel) across sound sets are preserved from listener to listener. She further claimed that EArel appeared to be related to the duration of elements that composed a sequence. The existence of EArel is investigated for four sound sets: CV nonsense syllables and pitch patterns that were composed of 50-, 80-, or 120-ms tones. The paradigm was target monitoring, a Yes/No task in which listeners attended to only one ear and listened for the presence of a target signal. The results failed to confirm that listeners have a consistent relative ear advantage related to element duration for nonspeech sound sets. PMID- 1737892 TI - Ultrasonic heating of lung tissue. AB - Tests with mice show that lung tissue is not selectively heated in comparison with other soft tissues and that lung has an efficient mechanism for dissipating that heat which is produced. Temperatures measured with a fine thermocouple placed at the outer surface of the mouse lung show approximately 1 degree C total rise in temperature in the living animal for an incident intensity of 1 W/cm2 (4 MHz, unfocused sound field). PMID- 1737893 TI - Temperature dependences of the acoustic nonlinearity parameter B/A of aqueous solutions of amino acids. AB - A differential technique for evaluating the molar increments of the nonlinearity parameter B/A has been employed for investigations of aqueous solutions of the amino acids glycine, alanine, norvaline, norleucine, arginine monohydrochloride, and lysine monohydrochloride in the temperature range 18 degrees C-45 degrees C. Some regularities of temperature dependencies of the nonlinearity parameter B/A of hydration shells of charged and aliphatic groups have been found. Contributions of these groups to the value of B/A molar increments of solute versus temperature have been estimated. PMID- 1737894 TI - 41st annual scientific session of the American College of Cardiology. Dallas, Texas, April 12-16, 1992. Abstracts. PMID- 1737895 TI - Putting nutrition on the grocery store shelf. PMID- 1737896 TI - Shaping a success story: dietetics in Taiwan. PMID- 1737897 TI - Obesity treatment: worshiping the "scale god". PMID- 1737898 TI - Trigeminal neuralgia: can one case report support a treatment recommendation? PMID- 1737899 TI - Nutrition screening initiative: development and implementation of the public awareness checklist and screening tools. PMID- 1737900 TI - Public health nutrition practices to prevent low birth weight in eight southeastern states. AB - This study was conducted to identify current public health nutrition practices for the prevention and treatment of low-birth-weight (LBW) infants in eight southeastern states. Nutrition personnel (n = 1,054) were mailed a 51-item questionnaire with three parts that sought information on the respondents' professional backgrounds and employment status and on practice and standards of care for women before and during pregnancy and of LBW infants. Results based on a 62% response rate indicated 73% had worked in public health nutrition for 2 to 9 years, 56% were direct care providers, and 51% had bachelor's degrees. Only 40% of respondents indicated that their agencies had prepregnancy nutrition intervention protocols, whereas 89% indicated that they had high-risk pregnancy screening protocols and 91% indicated that they had high-risk treatment protocols. More than 91% indicated that their treatment protocols included guidelines for weight gain, preparation of nutrition care plans, and assessment of dietary and biochemical factors, health behavior, and obstetric history. Only 73% indicated inclusion of assessment of educational level. Nutritionists saw high-risk pregnant women (or those at risk for preterm labor) slightly more frequently during pregnancy than they saw low-risk women; however, the range (0.9 to 3.8 vs 0.5 to 2.3) and average (2.0 vs 1.2) number of visits for both groups differed only slightly. Nutritionists counseled women and charted in the medical record more frequently than they used nutrition care plans. To reduce LBW, nutritionists should implement treatment protocols and monitor high-risk women closely. The relationship between pre-pregnancy nutrition interventions and birth weight should be investigated. PMID- 1737901 TI - Food intake of very obese persons: quantitative and qualitative aspects. AB - To document the caloric intake of very obese persons and investigate the food choices and dietary composition that maintain severe obesity, we studied the self selected food intake required to maintain stable weight in two groups of very obese subjects: 11 inpatients with a mean weight 181% above desirable body weight and 35 outpatients with a mean weight 125% above desirable body weight. Qualitative and quantitative food intake were evaluated using records obtained on the hospital metabolic ward for the inpatients and using self-recorded food records for the outpatients. Absolute caloric intake in both groups was greater in proportion to the degree of obesity (deviation from desirable body weight); caloric intake per unit of lean body mass (kilocalories per gram urinary creatinine) was constant regardless of the degree of obesity and was essentially the same as that of normal nonobese persons. Food records indicated that the obese subjects maintained their high caloric intake by consuming mostly foods of high caloric density, with occasional binge eating. They largely avoided foods of low intrinsic energy density and modified-calorie foods, ie, foods with decreased fat, nonnutritive sweeteners, or fillers. By substituting foods of lower caloric density for usual food choices from the same food group, obese persons could decrease caloric intake by 20% and increase potential for notable weight loss. PMID- 1737902 TI - Building a strategic forecasting system for hospital foodservice operations. AB - Forecasting, which involves the manipulation of operational data, is a critical task in foodservice management. We propose a strategic forecasting system for foodservice management, which may be expedited by using decision support systems. The most notable potential for improved forecast performance and decision flexibility may rest with increasing forecasting information. This article provides a framework for building a strategic forecasting system that can help managers select and use appropriate forecasting models for foodservice operations. PMID- 1737903 TI - Hemochromatosis and dietary iron supplementation: implications from US mortality, morbidity, and health survey data. AB - Trends in the mortality rates, morbidity rates, and hematologic screening parameters for hemochromatosis in the United States over the past 20 years were examined to assess whether dietary iron supplementation is a precipitating factor for hemochromatosis. From 1968 through 1987, there was an increase in the overall hemochromatosis mortality rates attributable to white women. From 1979 through 1987, the hospitalization rates for hemochromatosis ranged from 4 to 13 per 100,000 persons in Medicaid data (1984) and the National Hospital Discharge Survey (1979-1987) and are similar to estimates in the literature from 1955. Although the iron nutritional status of persons under 55 years of age increased from the first to the second National Health and Nutrition Examination Survey, there was no corresponding increase at the 95th percentile in the hemochromatosis screening parameters--serum iron concentration and transferrin saturation. A hypothetical scenario was used to examine the progression from homozygous gene frequency to phenotypic expression. It is concluded that clinical hemochromatosis is rarer than prevalence estimates of 100 to 500 per 100,000 persons predicted by gene frequency. In addition, there is no strong evidence of an increase in hemochromatosis from mortality, morbidity, or health survey data, which implies that dietary iron supplementation begun in 1940 has not accelerated manifestations of hemochromatosis. Any increase in hemochromatosis since iron fortification can probably be attributed to accuracy in diagnosis and enhanced awareness of the disease by physicians rather than to environmental factors. PMID- 1737904 TI - Effect of maternal employment on the quality of young children's diets: the CSFII experience. PMID- 1737905 TI - Using early weight gain and other nutrition-related risk factors to predict pregnancy outcomes. PMID- 1737906 TI - Reliability of direct observation of schoolchildren's consumption of bag lunches. PMID- 1737907 TI - Recruitment and retention of volunteers in a dietary methodology study. PMID- 1737908 TI - Teaching computer-aided nutrition assessment via self-instructional modules. PMID- 1737909 TI - Immunosuppressive therapy for primary biliary cirrhosis. PMID- 1737910 TI - Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications. AB - The implications of hepatitis B virus (HBV) reinfection after liver transplantation were studied in 29 patients followed for 1.7-15 years. Of 20 patients with HBV infection alone, nine were HBeAg and HBV DNA seronegative and 11 had evidence of HBV replication as measured by HBeAg or HBV DNA seropositivity. Nine patients had co-existing HBV and delta virus (HDV) infection. Five patients became HBsAg seronegative after transplantation (four immediately and one after an hepatitic episode). Of the 20 patients with HBV infection alone, 17 had evidence of viral replication after transplantation with markedly increased HBV DNA levels. Five patients with HDV infection had HBV DNA in serum, but in significantly lower amounts than in those with HBV infection alone. Twenty-five episodes of graft dysfunction attributed to recurrent HBV infection occurred in 19 patients (65.5%). Thirteen episodes (in 12 patients) were self-resolving acute hepatitic illnesses. Six patients had a rapidly progressive illness leading to graft loss within 6 weeks, with the distinctive histological features termed fibrosing cholestatic hepatitis (FCH). Liver function tests in these patients showed markedly abnormal serum bilirubin and prothrombin times, but only modest increases in serum transaminase levels. An additional six patients lost their graft as a consequence of HBV recurrence through various pathogenetic mechanisms including possible (but unproven) FCH, chronic active hepatitis or late-onset hepatic failure. Co-existing HDV infection appeared to confer some medium-term protection from graft loss. PMID- 1737911 TI - Mechanism of bile acid-induced HCO3-(-)rich hypercholeresis. An analysis based on quantitative acid-base chemistry. PMID- 1737912 TI - Endoscopic management of biliary tract obstruction in the 1990s. PMID- 1737913 TI - Serial determination of type III procollagen amino propeptide serum levels in patients with histologically progressive and non-progressive primary biliary cirrhosis. AB - We examined the value of serum procollagen III amino propeptide (PIIIP) for predicting the histological progression of primary biliary cirrhosis (PBC). Serial PIIIP measurements were obtained for nine patients with histologically progressive PBC and nine patients with histologically stable early disease, assessed by repeated liver biopsies and followed for up to 13 years. The means of the follow-up PIIIP concentrations were elevated in 39% of the cases; moreover, PIIIP levels were elevated at least once during follow-up in 72% of the cases. Mean follow-up PIIIP concentrations did not differ significantly between progressive and non-progressive patients. In addition, in the progressive group, histological progression was not reflected by PIIIP levels. No difference was found between the serum PIIIP levels corresponding to the histological stages I, II and III. The individual coefficients of the correlation between serum PIIIP and biochemical variables (bilirubin, alkaline phosphatase, ASAT, albumin) and histology showed a wide distribution without a consistent trend towards positive or negative. Treatment with cyclosporin A or cyclosporin A combined with prednisone did not influence serum PIIIP levels. Treatment with penicillamine combined with prednisone, however, resulted in a significant decrease in PIIIP concentrations (p less than 0.05). We conclude that serum PIIIP measurements are of no value for predicting the histological progression of PBC. PMID- 1737914 TI - Uptake of organic anions by isolated rat hepatocytes. A classification in terms of ATP-dependency. AB - Uptake of organic anions into isolated rat hepatocytes was studied to examine their ATP dependency. In the presence of rotenone (0.2 microM), the initial velocity of the uptake (Vo) of dibromosulfophthalein (DBSP; 10 microM), 1-anilino 8-naphthalenesulfonate (ANS; 10 microM) and benzylpenicillin (PCG; 0.02 microM) was reduced to 60-70% of the control value, while that of bromosulfophthalein (BSP; 10 microM), rose bengal (RB; 10 microM) and bromophenol blue (BPB; 10 microM) was not affected. Furthermore, we examined the inhibitory effect of rotenone on the uptake at equilibrium of non-metabolizable ligands (DBSP, BPB and RB). The uptake of these ligands reached equilibrium at 30 min with a cel-to medium concentration ratio (C/M ratio) of 75, 37 and 126, respectively. The C/M ratio at equilibrium of DBSP was reduced by rotenone to approx. 60% of the control value, while that of BPB and RB was not reduced. Other metabolic inhibitors such as sodium azide (10 mM) and carbonylcyanide-p trifluoromethoxyphenylhydrazone (FCCP; 10 microM) also reduced the Vo of DBSP and PCG, while the uptake of BSP and RB was not reduced by these inhibitors. These results indicate that organic anions can be classified into two groups according to whether they are taken up by hepatocytes in an ATP-dependent manner, i.e., via active transport or in an ATP-independent manner, i.e., via facilitated diffusion. DBSP, PCG and ANS belong to the former group, whereas BSP, BPB and RB belong to the latter. PMID- 1737915 TI - Autoantibodies in experimental autoimmune hepatitis. AB - Experimental autoimmune hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of autoimmune hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in autoimmune chronic active hepatitis patients. We conclude that autoantibodies arise in experimental autoimmune hepatitis but that these autoantibodies do not play a critical role in the pathogenesis of the disease. PMID- 1737916 TI - Utilization of ATP-depleted cells in the analysis of taurocholate uptake by isolated rat hepatocytes. AB - The usefulness of ATP-depleted rat hepatocytes in transport studies was examined. ATP-depleted hepatocytes were prepared by incubating cell suspensions with 30 microM rotenone. In ATP-depleted hepatocytes, plasma membrane permeability was increased and mitochondrial membrane potential decreased, while both intracellular volume and pH remained normal. Furthermore, in the presence of valinomycin, the initial uptake rates of 3H-tetraphenyl phosphonium (TPP+) with varied medium concentrations of potassium were predicted according to the Goldman Hodgkin-Katz equation, which demonstrated that a potassium diffusion potential could be produced in this system. Using the thus-characterized ATP-depleted cells, the uptake mechanism of taurocholate was investigated. In the presence of an inwardly directed Na gradient, the taurocholate uptake was markedly stimulated and bile acid was transiently accumulated at a concentration 3-times higher than at equilibrium ('overshoot') in ATP-depleted cells. No overshoot was observed in viable cells, however, which suggests that in ATP-depleted cells the Na gradient, a driving force for taurocholate uptake, decreased with time. In both viable and ATP-depleted cells, the relationship between medium concentrations of Na and the Na-dependent initial uptake rate were sigmoidal, and the Hill coefficients were close to 2. The Na-dependent initial uptake rate of taurocholate was stimulated by a valinomycin-induced inside negative potassium-diffusion potential in ATP depleted cells, and the movement of a 'one plus' (as a net) charge was revealed by fitting the data to the Goldman-Hodgkin-Katz equation. These results support the hypothesis that sodium-coupled hepatic uptake of taurocholate occuthrough an electrogenic process with the stoichiometry of 2 Na: 1 taurocholate, although this issue is controversial. In the presence of an outwardly directed sodium gradient, efflux of taurocholate from ATP-depleted cells was not stimulated. Consequently, the physiological transport vector of taurocholate from blood to cell is not only due to the direction of the sodium gradient (blood to cell) but also to membraneous orientation of transport carriers. In conclusion, kinetic analysis using ATP-depleted hepatocytes allowed the formulation of a new approach to clarify the as yet unresolved issues concerning transport stoichiometry and the mechanism for vectorial transport of taurocholate. PMID- 1737917 TI - Effect of the terpenic compound epomediol on biliary secretion and bile composition in the rat. AB - The aim of the present investigation was to define the role of the synthetic terpenoid epomediol on biliary secretion in rats recovered from anaesthesia, in stabilized conditions and receiving an intravenous infusion of Na+ taurocholate (120 or 240 nmol.min-1 per 100 g body wt.) or physiologic saline (NaCl 0.16 M). Epomediol was administered at the rate of 20 and 50 mg.kg-1 per h, through a second syringe connected to the same vein catheter. Bile flow was increased up to 67% according to the model. The effect of epomediol is dose-dependent, associated with enhanced Na+ transport into bile and with an increased anionic gap. The extent of epomediol action also changes according to the different rates of bile acid secretion. At low secretory rates a greater choleretic action was observed with epomediol. The effect was negligible for a secretion of bile acids above 350 nmol.min-1 per 100 g body wt. Excretion into bile of the epomediol glucuronide was not hampered by high Na+ taurocholate output. This suggests that there is no competition of the two anions for a common excretory pathway at the studied rates. The effect of epomediol seems due to a mechanism of action both independent and additive to the mechanism for bile acids. The presence of additivity of the two choleretic mechanisms at low flow and bile acid secretion and the loss of action at high secretory rates, suggests that the maximal capacity of passage for water into bile was reached. PMID- 1737918 TI - Experimental dissolution of pigment gallstone material using alkaline EDTA and adjuvant bile salts/non-bile salt detergents, thiols and urea, with respect to local chemolitholysis. AB - In order to enhance the dissolution capacity and the kinetics of topical solvents used in local pigment chemolitholysis, a series of dissolution experiments was performed with intact brown and black pigment stones and with standardized solutes such as pigment stone powder and compressed powder (static disc method). The basic dissolution medium was a 0.1 M boric acid/sodium carbonate buffer (pH 9.5), and the basic lytic agent was EDTA-4Na, working satisfactorily at 1-3 g/dl. It could be demonstrated that the dissolution efficiency of this basic solvent was enhanced significantly in the presence of a detergent (surfacant) and of urea. Among the detergents the zwitterionic (e.g., Sulfobetain-12) and the nonionic types (e.g., a polyoxyethylene ether like Lubrol PX) proved to be most effective. The adjuvant effect of the investigated thiols was disappointing. Only dithioerythritol/dithiothreitol and N-acetylcysteine showed any moderate, if consistent, lytic activity. The highest dissolution rates in dissolving compressed powder standards (disc method) were achieved with the ternary solvent (1% w/v EDTA/80 mM Lubrol PX/1 M urea, pH 9.5). Intact black pigment stones, well known as problematic candidates for chemolitholysis, could be largely dissolved up to approximately 70% of their initial weight. This was not merely a physical disintegration, but a chemical process. PMID- 1737919 TI - Higher levels of serum aminoterminal type III procollagen peptide, and laminin in alcoholic than in nonalcoholic cirrhosis of equal severity. AB - In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 +/- 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 +/- 1.5, n.s.) with only slight evidence for inflammation: GOT 28 +/- 22 vs. 24 +/- 21 U/l; GPT 24 +/- 23 vs. 31 +/- 28 U/l; gamma-globulins 24 +/- 8 vs. 22 +/- 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 +/- 19 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites. PMID- 1737920 TI - The effect of an eucaloric high carbohydrate diet on circulating levels of glucose, fructose and non-esterified fatty acids in patients with cirrhosis. AB - Twelve cirrhotic patients and six controls were fed an eucaloric high carbohydrate (CHO) diet for 3 days. Fasting serum triglyceride (TG), non esterified fatty acids (NEFA), glucose, insulin and glycerol were estimated daily. On the 3rd day of the study we measured NEFA, glucose, insulin, and fructose every 45 min from 07:45 h until 19:45 h, and then every 4 h until 07:45 h the next day. The patients were divided into two groups of six on the basis of plasma lecithin-cholesterol acyltransferase (LCAT) activity: group A cirrhotics (with good liver function--LCAT activity: 40.6-65.7 nmol.ml-1.h-1; mean 48.5), and group B (poor liver function--LCAT: 23.7-32.3; mean 27.4). On the high CHO diet there was an increase in the fasting serum TG with a peak after 2 or 3 days. The increase in serum TG in controls was greater (p less than 0.01) than in either group of cirrhotics. In the controls and in group A most of the extra TG was carried in VLDL; in group B only 39% of the TG increment was found in VLDL. Fasting NEFA fell with 3 days of CHO feeding in the control group (p less than 0.01); they were unchanged in group A, and rose in group B to a significantly higher level than in controls (p less than 0.01). During day 3 when a high CHO diet was fed plasma NEFA levels fell in cirrhotics, and for most of the day the mean NEFA concentration in group B patients was significantly (p less than 0.05) lower than in normals. On day 3 glucose and fructose levels rose after each meal- much more in cirrhotics than in controls (and more in group B than in group A), and for most of the day they were significantly higher in group B patients as compared to the controls (glucose p less than 0.01, fructose p less than 0.001). Our results supported the hypothesis that plasma NEFA would be lower following high CHO meals in cirrhotics than in controls. This suggests that a high NEFA utilisation, which occurs in fasting cirrhotics, is not present throughout the day. Following a CHO meal, we suggest that tissues derive energy directly from the dietary sugars which are present in high concentration during the period of absorption and that this reduces the post prandial requirement for NEFA. PMID- 1737921 TI - Hepatic haemodynamics and microvascular architecture after portal venular embolization in the rat. AB - To clarify the relationship between hepatic damage and alterations of hepatic microvascular architecture and haemodynamics following portal venule occlusion, the present study was performed in rats which had been injected into the portal vein with 700,000 plastic beads (30-35 microns in diameter). When the occluded segment of the portal venule was short, infarction did not occur because of the prompt development of vascular channels bypassing the obstructed venules. On the other hand, when the occluded segment was long, infarction usually occurred. In this case, formation of collateral vascular channels began as dilatation of the sinusoids in the vicinity of the occluded portal venules and increased in diameter and developed into new portal venules in 5 days. Increased portal vascular resistance after embolization was normalized after 5 days in parallel with the progression of reconstruction of vascular channels. Reduced bile production returned to a normal level 3 days after embolization. Necrotic tissue was resorbed completely and replaced by fibroblasts 5 days after embolization. These findings indicate that the development of infarct following portal venule occlusion depends on the length of the occluded segment, and that hepatic microvasculature has a great capacity for adaptation and rapid reconstruction of vascular channels which leads to speedy recovery from hepatic circulatory disturbances and resulting hepatic damage. PMID- 1737922 TI - The effects of alcohol use on rebleeding and mortality in patients with alcoholic cirrhosis following variceal haemorrhage. AB - The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices. PMID- 1737923 TI - Interaction of antigenic peptides with MHC class I molecules on living cells studied by photoaffinity labeling. AB - Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of antigenic peptides with murine MHC class I molecules on living cells. Photoreactive derivatives were prepared by N-terminal amidation with iodo, 4-azido salicylic acid of the Kd restricted Plasmodium berghei circumsporozoite (P.b. CS) peptide 253-260 (YIPSAEKI) and the Db-restricted Adenovirus 5 early region 1A (Ad5 E1A) peptide 234-243 (SGPSNTPPEI). As assessed in functional competition experiments, both peptide derivatives retained the specific binding activity of the parental peptides for Kd or Dd, respectively. The P.b. CS photoprobe specifically labeled Kd molecules on P815 (H-2d) cells, but failed to label RMA (H-2b) cells. Conversely, the Ad5 E1A photoprobe specifically labeled Db molecules on RMA cells, but failed to label P815 cells. When the two photoprobes were tested on a panel of Con A-activated spleen cells expressing 10 different H-2 haplotypes, significant photoaffinity labeling was observed only on H-2d cells with the P.b. CS photoprobe and on H-2b cells with the Ad5 E1A photoprobe. Labeling of cell-associated Kd or Db molecules with the photoprobes was specifically inhibited by antigenic peptides known to be presented by the same class I molecule. Photoaffinity labeling of Kd with the P.b. CS photoprobe was used to study the dynamics of peptide binding on living P815 cells. Binding increased steadily with the incubation period (up to 8 h) at 37 degrees C and at ambient temperature, but was greatly reduced (greater than 95%) at 0 to 4 degrees C or in the presence of ATP synthesis inhibitors. The magnitude of the labeling was twofold higher at room temperature than at 37 degrees C. In contrast, binding to isolated Kd molecules in solution rapidly reached maximal binding, particularly at 37 degrees C. Dissociation of the photoprobe from either cell associated or soluble Kd molecules was similar, with a half time of approximately 1 h at 37 degrees C, whereas the complexes were long-lived at 4 degrees C in both instances. PMID- 1737924 TI - The class II MHC-restricted presentation of endogenously synthesized ovalbumin displays clonal variation, requires endosomal/lysosomal processing, and is up regulated by heat shock. AB - LB27.4 cells (a B lymphoblastoid APC) were transfected with a plasmid containing an OVA cDNA. Functional analysis of six independent clones yielded three patterns of MHC-restricted presentation of the endogenously synthesized OVA. A clone displayed either: 1) strong class I and class II-restricted presentation, 2) strong class I but little or no class II-restricted presentation or, 3) only a modest class I-restricted presentation. There was no clonal variation in class II restricted presentation of exogenous Ag or in the amount of surface class I or II molecules. Heat shock increased the presentation of endogenous but not exogenous Ag with class II. These results indicate that an endogenously synthesized Ag both constitutively and during heat shock can gain access to the class II, MHC restricted, presentation pathway. The amount of OVA synthesized by a cell correlated with whether OVA-class II complexes were detected. However, the amount of OVA secreted into the extracellular fluid was not sufficient to sensitize APC, which suggests that endogenously synthesized OVA enters the class II pathway of Ag presentation by an intracellular route rather than by an extracellular/reuptake route. Also, the functional and quantitative analysis of the clones suggests that endogenously synthesized OVA was presented more efficiently with class I as compared to class II-MHC molecules. Leupeptin and chloroquine inhibited the class II-restricted presentation of endogenously synthesized OVA. Together these results indicate that endogenously synthesized OVA can gain access to an endosomal/lysosomal compartment via an intracellular route and be processed and presented in association with class II-MHC molecules. PMID- 1737925 TI - A toxic shock syndrome toxin-1 peptide that shows homology to mycobacterial heat shock protein 18 is presented as conventional antigen to T cells by multiple HLA DR alleles. AB - We observe that PBMC from most adults (16 of 18 subjects tested) show a small but significant in vitro proliferative response to a 30-amino acid-long peptide (peptide 2, amino acids 34-63) derived from toxic shock syndrome toxin. By contrast, PBMC from newborn blood and thymocytes do not proliferate to this peptide, and furthermore, peptide 2 did not displace the binding of radiolabeled TSST-1 to MHC class II positive cells, nor did it induce IL-1 beta mRNA in monocytes, indicating that this peptide does not behave as a superantigen. Proliferation of PBMC to peptide 2 could be blocked by anti-HLA-DR, but not by anti-HLA-DP or DQ mAb, suggesting that HLA-DR molecules are the restriction elements for the recognition of this peptide by T cells. This premise was further confirmed by demonstrating that mouse L cells transfected with human HLA-DR, but not HLA-DP or DQ molecules, supported the proliferation of purified T cells to peptide 2. Studies with subjects of known HLA-DR types showed that all types tested are capable of responding to this peptide, PBMC from adults exposed to mycobacterial Ag showed significantly better proliferative response to peptide 2 than unexposed adults. Studies with truncations of this peptide suggest that a "core" region of eight amino acids that is conserved between low m.w. heat shock proteins and peptide 2 may be critical to T cell recognition of this peptide. The universal presentation of peptide 2 by HLA-DR molecules may contribute to the widespread natural immunity observed against toxic shock syndrome toxin. PMID- 1737926 TI - Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies. AB - Human PBL from vaccinated healthy blood donors, which was transplanted i.p. into mice with severe combined immunodeficiency (SCID), exhibited an Ag-dependent humoral Ir against tetanus toxoid. This Ir was dose dependent and was completely abrogated by immunizing with large amounts of Ag, suggesting a high dose tolerization of the B cells. A dose-dependent selection of specific, high affinity B clonotypes was also suggested, since immunization with low concentrations of tetanus toxoid produced antisera with higher avidity than immunizations using a high dose of Ag. The production of human Ig and the clonal outgrowth of normal human B cells in the SCID mouse was strongly down-regulated by human NK cells. Human immune B lymphocytes were also recovered from immunized SCID mice and transformed with EBV, yielding lymphoblastoid cell lines producing high affinity antitetanus human IgG antibodies. These results suggest that SCID mice, repopulated with human PBL, can constitute a functional model of several parameters of a normal human humoral Ir and can provide a source of immune B cells for the production of human mAb. PMID- 1737927 TI - Allogeneic chimerism in scid mice after neonatal transfer of bone marrow. AB - Allogeneic chimeras are valuable tools for studies of complex immune cell interactions in vivo. Mice with severe combined immune deficiency (scid) should be ideal hosts for chimerism with allogeneic bone marrow cells as these animals lack mature T and B lymphocytes capable of reacting against donor alloantigens. However, it has been difficult to achieve full reconstitution of adult scid mice even using coisogenic bone marrow grafts without prior irradiation of the recipient. We explored ways to generate complete reconstitution of scid mice with allogeneic bone marrow. Unirradiated adult scid recipients of allogeneic bone marrow were only marginally reconstituted. Adult scid mice pretreated with 250 R were reconstituted with allogeneic bone marrow as measured by serum IgM concentration, peripheral lymphoid cellularity, and mitogen responses, but a potentially important immunologic deficit was found in these mice: 250 R caused a 70% loss of scid macrophages and dendritic cells which persisted at least 5 months. By contrast, when scid mice were injected i.p. with allogeneic bone marrow within the first 24 h after birth, rapid and complete reconstitution of both T and B cell lineages was achieved, and the animals had APC that were both donor and host in origin. Considering the extent and duration of engraftment (43 wk) by allogeneic cells in neonatally transplanted scid mice, it was anticipated that their bone marrow would be chimeric. However, the bone marrow contained very few donor-derived cells, suggesting that lymphopoiesis may be taking place in other organs in these chimeras. PMID- 1737928 TI - Transforming growth factor-beta enhances the M-CSF and GM-CSF-stimulated proliferation of macrophages. AB - Transforming growth factor-beta (TGF-beta) has been shown to regulate the proliferation and function of several different cell types in the immune system. We have examined the effect of TGF-beta on the proliferation of murine macrophages in liquid culture. TGF-beta by itself did not induce proliferation of differentiated (7 days in culture) bone marrow-derived macrophages (BMM). In the presence of M-CSF, TGF-beta enhanced the proliferation of differentiated BMM and elicited peritoneal macrophages but had an inhibitory effect on the proliferation of nonadherent BMM (3 days in culture). The effect of TGF-beta was not restricted to M-CSF-dependent proliferation but was also observed for GM-CSF-dependent proliferation. The autocrine production of TGF-beta appeared to contribute to the proliferation of BMM. The addition of antibody against TGF-beta inhibited M-CSF- and GM-CSF-dependent proliferation 32% and 28%, respectively. In bone marrow, TGF beta may be an important negative regulator of macrophage proliferation; whereas, in the tissues, TGF-beta may enhance macrophage proliferation. PMID- 1737929 TI - Transforming growth factor-beta 1 and IL-4 regulate the adhesiveness of Peyer's patch high endothelial venule cells for lymphocytes. AB - The adhesion of lymphocytes to endothelial cells lining the postcapillary high endothelial venules (HEV) is the first step in their emigration from the bloodstream into lymph nodes and Peyer's patches (PP). We have recently shown that the adhesiveness of cultured rat lymph node and PP HEV cells for thoracic duct lymphocytes can be increased significantly by pretreatment with TNF-alpha, IFN-gamma, and IL-4. In the present study we investigated the role of transforming growth factor-beta 1 (TGF-beta) on the adhesiveness of nonstimulated and cytokine-stimulated PP HEV cells for rat lymphocytes. The results indicated that at picomolar concentrations, TGF-beta significantly (p less than 0.001) decreased the ability of PP HEV cells to adhere 51Cr-labeled rat lymphocytes. Maximal inhibition was observed with a TGF-beta dose of 0.5 ng/ml and an incubation time of 6 to 12 h. TGF-beta did not affect the morphology of HEV cells and had no adverse effect on their viability. Moreover, the decrease in HEV adhesiveness by TGF-beta was reversible, with lymphocyte binding returning to control level 24 h after removal of the cytokine. The specificity of TGF-beta was confirmed by the ability of neutralizing anti-TGF-beta 1 antibody, but not control serum, to abolish the inhibitory properties of the cytokine. In addition, TGF-beta completely abrogated the increased adhesiveness of PP HEV cells normally induced by TNF-alpha or IFN-gamma. In contrast, TGF-beta had no effect on the stimulating effects of IL-4. Moreover, preincubation of PP HEV cells with TGF beta did not alter the ability of these cells to respond to IL-4. Importantly, the adhesion of rat lymphocytes to IL-4-stimulated PP HEV cells can be blocked by pretreatment of lymphocytes with the PP-homing receptor-specific 1B.2.6 antibody whereas pretreatment of human mononuclear cells with anti-very late activation antigen-4 alpha antibody inhibited only partially the binding of these cells to the IL-4-stimulated PP HEV monolayers. Taken together, these findings strongly suggest that TGF-beta and IL-4 play important regulatory roles in lymphocyte-HEV adhesion and that the stimulatory effect of IL-4 is mediated at least in part through the increased expression of organ-specific ligands on HEV cells. PMID- 1737930 TI - Human IL-3 induction of c-jun in normal monocytes is independent of tyrosine kinase and involves protein kinase C. AB - We have used normal human monocytes as a model system to begin elucidating the signal transduction mechanism associated with the IL-3R. Normal human monocytes deprived of human serum and CSF become quiescent in vitro. Stimulation of these cells with rIL-3 induces expression of the c-jun protooncogene, as detected by Northern blotting of total monocyte RNA. This protooncogene is also induced in these cells by phorbol ester through direct stimulation of protein kinase C. Concentrations of the protein kinase C inhibitor I-(5-isoquindinyl-sulfonyl)-2 methylpiperazine (H-7) between 30 and 100 microM (5-20 x Ki) inhibit this induction by phorbol ester. The same concentration-range of H-7 completely inhibited the induction of c-jun by human IL-3. A structural analog of H-7 designated HA-1004 preferentially inhibits cyclic nucleotide-dependent protein kinase rather that protein kinase C. HA-1004 at 5 to 20 x Ki did not inhibit IL-3 induced c-jun mRNA accumulation. Further 30 microM genistein that is an effective inhibitor of cellular tyrosine kinases did not inhibit IL-3-induced c-jun expression. Immunoprecipitation of lysates from [32P]orthophosphate labeled cells with antiphosphotyrosine polyclonal antibody showed that IL-3-stimulated phosphorylation of a 70-kDa protein and a 110-kDa protein on tyrosine, and that these protein phosphorylations were completely inhibited by 30 microM genistein. As further confirmation that IL-3 is stimulating protein kinase C in human monocytes we have found that IL-3 stimulates phosphorylation of the unique protein kinase C substrate myristoylated alanine-rich C kinase substrate in these cells. It is therefore likely that the interaction of IL-3 with its receptor generates diacylglycerol and stimulates the Ca2+/phospholipid-dependent protein kinase C. PMID- 1737931 TI - IL-10 inhibits human T cell proliferation and IL-2 production. AB - Human IL-10 has been reported previously to inhibit the secretion of IFN-gamma in PBMC. In this study, we have found that human IL-10 inhibits T cell proliferation to either mitogen or anti-CD3 mAb in the presence of accessory cells. Inhibited T cell growth by IL-10 was associated with reduced production of IFN-gamma and IL 2. Studies of T cell subset inhibition by human IL-10 showed that CD4+, CD8+, CD45RA high, and CD45RA low cells are all growth inhibited to a similar degree. Dose response experiments demonstrated that IL-10 inhibits secretion of IFN-gamma more readily than T cell proliferation to mitogen. In addition, IL-2 and IL-4 added exogenously to IL-10 suppressed T cell cultures reversed completely the inhibition of T cell proliferation, but had little or no effect on inhibition of IFN-gamma production. Thus, in addition to its previously reported biologic properties, IL-10 inhibits human T cell proliferation and IL-2 production in response to mitogen. Inhibition of IFN-gamma production by IL-10 appears to be independent of the cytokine effect of IL-2 production. PMID- 1737933 TI - HLA-Bw22: a family of molecules with identity to HLA-B7 in the alpha 1-helix. AB - Various HLA-B molecules exhibit serologic cross-reactions with HLA-B7, including HLA-B27, B40, Bw42, and Bw22. Of this group, primary structures for the three serologic subdivisions of HLA-Bw22, HLA-Bw54, Bw55, and Bw56, have yet to be determined. Here, we describe the nucleotide sequences of five distinctive HLA Bw22 alleles isolated from cells of different ethnic origins typed either for Bw54, Bw55, or Bw56. Heterogeneity in molecules typed as Bw55 and Bw56 was defined. The five HLA-Bw22 alleles form a closely related family that appears to have evolved by a series of simple gene conversion events, all of which alter the antigen recognition site of the encoded proteins. Of note, HLA-Bw54 is the product of a gene conversion between HLA-B and C alleles. All the Bw22 alleles encode an alpha 1-helix identical in amino acid sequence to that of HLA-B7 and Bw42, a feature almost certainly responsible for the serologic cross-reactivity of these molecules. Shared substitutions in the alpha 1-helix can also explain the cross-reactivity of Bw22 and B7 with B27. Patterns of amino acid substitution in the alpha 2-domain of Bw22 heavy chains correlate with certain antibody and T cell cross-reactivities, thereby implicating particular amino acids in their target epitopes. PMID- 1737932 TI - Chimeric and humanized antibodies with specificity for the CD33 antigen. AB - L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies. PMID- 1737934 TI - Expression of human IL-1 beta in Salmonella typhimurium. A model system for the delivery of recombinant therapeutic proteins in vivo. AB - The feasibility of using Salmonella typhimurium aroA mutant (SL3261) to deliver protein therapeutic agents was investigated in a murine model system. We have constructed an Escherichia coli expression plasmid designed to express the human protein IL-1 beta. This plasmid expresses IL-1 beta to high levels (greater than 30% total cell protein) in E. coli. In Salmonella the IL-1 beta is expressed constitutively to about 10% total cell protein, as verified by Western blotting analysis using polyclonal rabbit anti-IL-1 beta antibody. The protein is produced in a soluble and biologically active form. BALB/c mice administered orally or i.v. with S. typhimurium aroA mutants carrying the plasmid produced highly significant antibody responses against human IL-1 beta as determined by a solid phase RIA. Furthermore, mice injected with the construct were significantly protected against lethal gamma-irradiation (850 rad). This study therefore demonstrates that the vaccine strain of Salmonella mutants can also be used effectively to deliver therapeutic proteins in vivo. PMID- 1737935 TI - Stimulus-response coupling in monocytes infected with Leishmania. Attenuation of calcium transients is related to defective agonist-induced accumulation of inositol phosphates. AB - Mononuclear phagocytes infected with Leishmania have been shown to have defective responses to extracellular stimuli. To investigate the potential relationship of these findings to alterations in calcium-dependent signaling pathways, the regulation of [Ca2+]i concentrations was examined in human peripheral blood monocytes infected with amastigotes of Leishmania donovani. Measurements of [Ca2+]i in fura-2-loaded monocytes were made at the single cell level by microfluorimetry. In normal monocytes, resting [Ca2+]i was 56 +/- 2 nM (mean +/- SEM). In contrast, in monocytes infected with Leishmania there was an approximately twofold increase in basal [Ca2+]i (122 +/- 5 nM, p less than 0.01 vs control). Treatment of cells with pertussis toxin before infection did not abrogate infection-induced increases in basal [Ca2+]i, suggesting that this effect was not mediated via the activation of a G protein coupled to phospholipase C. However, elevated resting [Ca2+]i did correlate with increased rates of 45Ca2+ uptake by infected monocytes. As expected, in response to treatment with 10(-7) M FMLP, control monocytes showed rapid net increases in [Ca2+]i of 303 +/- 19 nM. In contrast, net transients of [Ca2+]i in infected monocytes in response to FMLP were attenuated to only 137 +/- 9 nM (p less than 0.01 vs control). This result was not related to excess buffering of [Ca2+]i in infected cells as both control and infected monocytes showed equivalent transients of [Ca2+]i in response to the calcium ionophore A23187. Rather, inhibition of agonist-induced calcium release in infected cells appeared related to defective generation of second messenger because compared to control cells labeled with myo-[2-3H]inositol, little accumulation of inositol 1,4,5 trisphosphate was detected in infected monocytes. Attenuation of inositol phosphate accumulation and calcium release in response to chemotactic peptide correlated with decreased FMLP-induced superoxide and hydrogen peroxide production by infected monocytes. These results provide direct evidence for defective regulation of [Ca2+]i and calcium-dependent signaling in Leishmania infected monocytes and provide a basis for understanding abnormalities in activation-related responses that involve signaling through Ca(2+)-regulated pathways. PMID- 1737936 TI - Two regions of the H-2 Dd promoter are responsive to dimethylsulfoxide in line 1 cells by a mechanism distinct from IFN-gamma. AB - The line 1 lung carcinoma is a spontaneous BALB/c tumor deficient in class I Ag expression at the protein and mRNA levels. Exposure of line 1 cells to 3% DMSO or IFN-gamma increases class I Ag protein and mRNA dramatically. We have examined the regulation of class I Ag induction by DMSO in line 1 cells. We found DMSO induces class I Ag expression in line 1 cells by a mechanism distinct from IFN, because the kinetics of class I Ag induction by these agents were dramatically different, 7 days vs 3 days, and DMSO did not act through an IFN second messenger. At the molecular level, class I H chain transcription in line 1 cells was low. Treatment with 3% DMSO or IFN-gamma increased H chain transcription four fold and sevenfold, respectively, indicating that class I H chain expression is regulated at the level of transcription in line 1 cells. Using reporter gene constructs, we mapped the regions in the Dd H chain promoter that increase H chain expression after DMSO treatment of line 1 cells. Two regions of the Dd promoter, D1, from -210 to -133 bp, and D2, from -125 to -61 bp, were found to be independently responsive to DMSO. These regions were also responsive to IFN-gamma in line 1 cells. However, consistent with our cellular results, DMSO and IFN induction of class I H chain expression differed at the molecular level as determined by D1 point mutations that diminished IFN-gamma responsiveness but did not alter induction by DMSO. Thus, DMSO appears to regulate class I transcription through multiple regions of the class I H chain promoter in line 1 cells by a mechanism distinct from IFN-gamma. PMID- 1737937 TI - Analysis of the AP-1 sites in the IL-2 promoter. AB - We have investigated the role of the two AP-1 sites, located at approximately 150 and -180 bp relative to the transcription start site, in induction of the IL 2 promoter through the TCR/CD3 complex. We show that only the proximal (-150 bp) AP-1 site is functional in vitro, as judged by its ability to bind nuclear proteins from T cells stimulated with Ag or anti-CD3 epsilon. The inducible nuclear proteins binding to this site have the characteristics of AP-1, as judged by their kinetics of induction, the ability to compete and be competed efficiently by a metallothionein AP-1 site oligonucleotide, and their reaction with antibodies to Fos and Jun proteins. Mutations in the proximal AP-1 site greatly diminish or abrogate induction of the IL-2 promoter, indicating that the site is also functional in vivo. Although the distal (-180 bp) AP-1 site is incapable of direct binding to nuclear proteins from activated T cells, a mutation in this site diminishes IL-2 promoter induction, suggesting that this site may also be functional in vivo. Cotransfection of a 5' IL-2-chloramphenicol acetyltransferase plasmid with c-Fos and/or c-Jun enhances the induction of IL-2 chloramphenicol acetyltransferase activity, confirming that the IL-2 promoter contains a functional AP-1 site. Both AP-1 sites may be targets for c-Fos action, as inferred from the results of experiments in which c-Fos was cotransfected with internal deletion mutants of the IL-2 promoter lacking either AP-1 site. Northern analysis indicates that mRNAs for at least six members of the Fos/Jun family (c fos, fosB, fra-1, c-jun, junB, and junD) are expressed in activated Ar-5 cells; thus the AP-1 sites of the IL-2 promoter may bind different dimeric Fos/Jun complexes at different times after T cell activation, perhaps mediating both positive and negative regulation of the IL-2 promoter. PMID- 1737938 TI - Characterization of complementary DNA clones encoding the rabbit IL-8 receptor. AB - IL-8 is a proinflammatory cytokine that functions as a chemoattractant for neutrophils. Recently, cDNA clones encoding the human neutrophil IL-8R were isolated by an expression cloning strategy. The amino acid sequence of the human IL-8R was sufficiently similar to a published sequence for an isoform of the rabbit FMLP receptor that we considered the possibility that the rabbit sequence might bind IL-8 as well. In order to establish its ligand specificity, we have isolated and characterized cDNA clones encoding the rabbit receptor. These cDNA clones, when expressed in mammalian cells, confer high affinity IL-8 binding (Kd = 3.6 nM), lack detectable binding of FMLP, and produce a transient increase in the intracellular Ca2+ concentration in response to IL-8 but not to FMLP. These data demonstrate that the reported rabbit FMLP receptor is the rabbit IL-8R, not an isoform of the FMLP receptor. In addition, the amino acid sequence of the rabbit IL-8R encoded by these cDNA clones differs at 23 amino acids (of 355) from that previously published. PMID- 1737939 TI - Differential expression of related HLA class II DQ beta genes caused by nucleotide variation in transcriptional regulatory elements. AB - HLA class II genes comprise a large multigene family with intra- and interlocus variation in structure and expression. Within this family of related genes, the HLA-DX alpha and beta loci (HLA DQA2 and DQB2) are highly homologous to functional HLA-DQ loci (HLA DQA1 and DQB1) but are frequently termed pseudogenes because DX gene transcription has not been observed, even in cells expressing HLA DQ. Analysis of upstream transcriptional regulatory elements for the DX beta and DQ beta genes identified a high degree of nucleotide homology, consistent with their derivation from a common ancestral class II gene. However, transient expression assays with plasmids utilizing promoter elements from the DX beta gene had no activity in transfected human B cells, in contrast to homologous DQ beta sequences. Reciprocal exchange of specific sequences from the DQ beta gene with those of the DX beta gene restored expression to wild-type DQ beta levels, as did mutagenesis of only three DX-specific nucleotides in the upstream regulatory region. These three nucleotides mark two binding sites for distinct nuclear DNA binding proteins that differentially recognize DQ beta and DX beta sequences. Transcription of these genes is critically dependent on interactions between these two upstream regulatory region sites which distinguish DX beta from its closely related homologue, DQ beta. PMID- 1737940 TI - Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma. AB - Tumor-derived chemotactic factors have been identified and suggested to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of a tumor-derived chemotactic factor molecularly identified as monocyte chemotactic protein (MCP; alternative designations are JE and MCAF) by gene transfer in a murine melanoma. After gene transfer, MCP-producing melanoma clones showed a marked (twofold) increase in the percentage of tumor-associated macrophages compared with control clones and with the parent line: for instance, the percentage of tumor-associated macrophages was 20.9 +/- 1.5, 29.4 +/- 2.3, and 47.6 +/- 2.5 for the parent line, the control V14 clone, and the MCP-producing L12 clone, respectively. MCP producing cells were tumorigenic but exhibited a slower growth rate in vivo (e.g., doubling time of 2.9 and 6.6 days for the control V14 and the MCP producing L12 clone, respectively) with a prolongation of survival time. The in vitro growth rate of melanoma clones was unaffected by MCP gene transfer. The same difference between MCP-producing and control cells, in terms of macrophage infiltration and growth rate, was detected after implantation in athymic mice. Whereas the in vivo growth rate of MCP-expressing tumors was slower, after i.m. inoculation of small cell numbers (10(2) cells) MCP-producing cells were slightly, but significantly, more tumorigenic. Local administration of IL-2 had modest, but definite, antitumor activity in this model; MCP-producing cells were less susceptible to local IL-2 immunotherapy. These results demonstrate that a tumor-derived chemotactic cytokine can indeed play a role in the regulation of mononuclear phagocyte recruitment in neoplastic tissues and emphasize how tumor associated macrophages can exert a dual influence in tumor-host interactions. PMID- 1737942 TI - On being a doctor at the year's beginning. PMID- 1737941 TI - A stromal cell-specific monoclonal antibody augments the stromal cell-dependent B lymphopoiesis. AB - We produced the mAb R25 against the stromal cell line ST2, which could support B lymphopoiesis in vitro. R25 enhanced the ability of ST2 to support B lymphopoiesis and precipitated molecules of 110 and 120 kDa (p110/120) from ST2 cell lysates. p110/120 were also expressed on other stromal and fibroblast cell lines but not on freshly isolated bone marrow hematopoietic cells, spleen cells, and lymphoid cell lines. However, R25 had no or weak effect on the stromal cell dependent myelopoiesis. Even under conditions in which bone marrow cells were separated from stromal cells with a membrane filter, R25 could augment the stromal cell-dependent B lymphopoiesis. However, R25 did not induce the increase of IL-7 mRNA of ST2 cells. Taken together, these findings suggest that the stromal cell surface molecules p110/120 are involved in the stromal cell dependent B lymphopoiesis and that certain soluble factors distinct from IL-7 may contribute to the p110/120-mediated B cell generation. PMID- 1737943 TI - Cost to society high for bogus DME orders. PMID- 1737944 TI - Push and pull: a look at the 1992 Georgia General Assembly. PMID- 1737945 TI - Medicare rip-off: DME fraud bleeds the system. PMID- 1737947 TI - Rescuing tort reform. PMID- 1737946 TI - Surgical treatment of spontaneous dissection of the internal carotid artery: case report and review. PMID- 1737949 TI - AMA provides AIDS guidelines for physicians. PMID- 1737948 TI - Diagnostic and therapeutic considerations in the management of atrial fibrillation. PMID- 1737950 TI - American Medical Association battles five threats to public health. PMID- 1737951 TI - AIDS and HIV testing. PMID- 1737952 TI - Different effects of the antiprogesterone RU486 on progesterone secretion by the corpus luteum of rats with 4- and 5-day oestrous cycles. AB - Administration of the antiprogesterone RU486 (2 mg/day) for 14 days to rats with a 5-day reproductive cycle resulted in an increase in both ovarian and pituitary weight in contrast with rats with a 4-day oestrous cycle. Luteal progesterone production decreased earlier in 4-day than in 5-day cyclic rats. Treatment of 5 day cyclic rats with antiprogesterone from the day of metoestrus onwards resulted in the advancement of the preovulatory prolactin surge by 24 h. Progesterone production by the corpus luteum was, however, not affected, indicating that in 5 day cyclic rats the corpora lutea are still functionally active at the time of the preovulatory surge of prolactin. They become, therefore, stimulated both in size and progesterone production. In contrast, the corpora lutea in 4-day cyclic rats are functionally inactive at the time of the preovulatory surge of prolactin, and prolactin acts luteolytically. In conclusion, the advancement of the preovulatory surge of prolactin by 24 h accounts, at least in part, for the increase in ovarian weight in 5-day cyclic rats after treatment with antiprogesterone. The results of these experiments do not agree with a direct effect of the antiprogesterone RU486 on progesterone secretion by the corpus luteum. PMID- 1737953 TI - Translational status of the insulin-like growth factor-I mRNAs in liver of protein-restricted rats. AB - Dietary protein restriction in young rats decreases serum insulin-like growth factor-I (IGF-I) concentrations and the amount of liver IGF-I mRNA, suggesting that regulation for the liver IGF-I gene expression in this model occurs at a pretranslational level. To determine whether there is also translational control, we assessed the association of the liver IGF-I mRNA transcripts with polysomes in livers of normally fed (15% dietary protein) versus protein-restricted (5% dietary protein) rats. One week of dietary protein restriction reduces serum IGF I concentrations by 54% and the amount of liver IGF-I mRNA by 35%, with the 7.5 kb size-class of IGF-I mRNA being the most affected (-48%). Protein restriction reduces the amount of the polysomal IGF-I mRNAs by 30%, a value in close agreement with the changes in total IGF-I mRNAs. Protein restriction is not associated with changes in the distribution of IGF-I mRNAs between the polysomal and non-polysomal fractions. All major size-classes of IGF-I mRNA transcripts (7.5, 4.7, 1.7, 0.9-1.2 kb) are associated with the polysomes in both dietary groups, suggesting involvement in the initiation phase of the IGF-I translation. We conclude that no untranslatable pool of IGF-I mRNAs is present in the liver of protein-restricted animals. Protein restriction, however, decreases slightly the mean size of polysomes. This decrease in ribosomal number associated with the IGF I mRNA could decrease translational efficiency. Our data suggest that dietary protein restriction does not impair the initiation of IGF-I mRNA translation. PMID- 1737954 TI - Relaxin increases the firing rate of supraoptic neurones and increases oxytocin secretion in the rat. AB - In urethane-anaesthetized ovariectomized rats, injection of porcine relaxin (7.5 and 15 micrograms/kg, i.v.) caused a sustained increase in circulating plasma oxytocin and vasopressin concentrations; 10 micrograms relaxin/rat i.v. produced a smaller but significant increase in plasma oxytocin concentration in conscious ovariectomized rats. A significant increase in oxytocin concentration and inhibition of the spontaneous milk-ejection reflex was also seen in anaesthetized (ovary intact) lactating rats following injection of relaxin (7.5 micrograms/kg, i.v.). To investigate whether relaxin acts by increasing the electrical activity of oxytocin neurones or by facilitating stimulus-secretion coupling in the pituitary, the electrical activity of neurones in the supraoptic nucleus was recorded in urethane-anaesthetized lactating rats and in ovariectomized rats. Porcine relaxin (10 micrograms/rat, i.v.) increased the firing rate of both oxytocin and vasopressin neurones in the supraoptic nucleus in lactating rats. The response to relaxin was unaffected by subsequent injection of naloxone (1 mg/kg, i.v.). Oxytocin neurones were also activated by injection of relaxin (10 micrograms/rat) into ovariectomized rats. Combining the electrophysiological data, the neuronal activation following relaxin was significantly correlated with the level of spontaneous activity prior to relaxin injection. The results show that relaxin acts centrally to increase circulating plasma oxytocin and vasopressin concentrations by an opioid-independent mechanism. PMID- 1737955 TI - Release of proinsulin from the human fetal beta cell. AB - beta cells in the human fetal pancreas are immature in that they release little or no insulin in response to nutrients, such as glucose. The aim of this study was to examine further the immaturity of these cells, specifically regarding the storage and release of the precursor of insulin, proinsulin. Explants of human fetal pancreas were cultured in vitro for 3 weeks. Levels of proinsulin remained relatively constant throughout at 0.04 +/- 0.002 (S.E.M.) pmol/mg per day with a molar ratio of proinsulin to insulin of 2.2 +/- 0.11%. This low ratio was slightly greater than that observed in culture medium conditioned by adult human islets (0.3 +/- 0.1%), but similar to that found in acid-ethanol extracts of cultured explants (1.4 +/- 0.3%). Passaging of human fetal pancreas for 3 months in diabetic nude mice, which should have caused some maturation of the fetal beta cell, did not change the proportion of proinsulin present. Culture of explants in the presence of 12-O-tetra-decanoylphorbol-13-acetate resulted in some inhibition of proinsulin release, but much less than that for insulin, so that the molar ratio increased to 15.4 +/- 1.6% from the control 3.5 +/- 0.3%. Static stimulation of cultured explants with 10 mmol Ca2+/l, 10 mmol theophylline/l, and these two agents together caused 15-, 4- and 10-fold enhancement respectively of proinsulin release; glucose, leucine, arginine and KCl had no effect. In contrast, all these agents caused significant insulin release, the last four to a much smaller extent (less than or equal to three fold) than the first three (10-, 19- and 65-fold respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737956 TI - Seasonal changes in plasma androgens, glucocorticoids and glucocorticoid-binding proteins in the marsupial sugar glider Petaurus breviceps. AB - An investigation spanning two breeding seasons was carried out to examine endocrine changes associated with reproduction in a wild population of the marsupial sugar glider Petaurus breviceps, a small arboreal gliding possum. Using techniques of equilibrium dialysis and polyacrylamide gel electrophoresis at steady-state conditions, a high-affinity, low-capacity glucocorticoid-binding protein was demonstrated in the plasma of Petaurus breviceps. Equilibrium dialysis at 36 degrees C using cortisol gave a high-affinity binding constant of 95 +/- 5.2 litres/mumol for a presumed corticosteroid-binding globulin (CBG) while the binding constant for the cortisol-albumin interaction was 3.5 +/- 0.4 litres/mmol. There was no difference between the sexes in the affinity of binding of cortisol to CBG; however, the cortisol-binding capacity underwent seasonal variation in both sexes. Progesterone was bound strongly to the presumed CBG while neither oestradiol nor aldosterone appeared to be bound with high affinity to P. breviceps plasma. In the males, peaks in the plasma concentration of testosterone coincided with the July-September breeding season in both years. A significant inverse relationship was shown to exist between the plasma testosterone concentration and the CBG-binding capacity. In both sexes an increase occurred in the plasma concentration of free cortisol during the first breeding season, a pattern which was not repeated in the subsequent breeding season, possibly due to a lower population density in that year. PMID- 1737957 TI - Gonadal steroids effect similar regulation of gonadotrophin subunit mRNA expression in both male and female rats. AB - Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-beta mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 +/- 4 ng/l) in males or testosterone (plasma testosterone 3.5 +/- 0.3 micrograms/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dot-blot hybridization. In males, oestradiol reduced LH-beta and FSH-beta but not alpha mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-beta remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced alpha and LH-beta to levels found in intact animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737958 TI - Comparison of the galactopoietic response to pituitary-derived and recombinant derived variants of bovine growth hormone. AB - Two studies were designed to examine the differences in galactopoietic potency of molecular variants of pituitary- and recombinant-derived bovine GH (bGH). The recombinant bGH molecules included amino-terminal and position-127 amino acid substitutions which are representative of two of the four natural pituitary variants or of partially degraded bGH molecules. Amino-terminal variants of bGH included methionine (Met1), alanine (Ala1), serine (Ser1) or deletion of four amino acids (delta 1-4). The delta 1-4 variants were representative of degradation products previously isolated in pituitary bGH preparations. In the first study, 54 lactating Holstein cows received i.m. injections of a buffer solution (control), pituitary-derived bGH, or recombinant-derived [Met1,Leu127] bGH, [Met1,Val127]-bGH, [Ala1,Leu127]-bGH, or [Ala1,Val127]-bGH. Cows received 25 mg bGH/day for 21 days. Substitution of the amino-terminal alanyl residue with methionine did not affect milk response. GH variants with Val127 elicited a greater milk response (8.5 kg/day) than Leu127 bGH variants (6.5 kg/day). The average milk response to the four recombinant bGH variants was 7.5 kg/day greater than controls compared with 4.4 kg/day for pituitary-derived bGH. In contrast, blood bGH concentrations were equivalent for pituitary and recombinant bGH treatments, approximately 20 micrograms/l more than control levels at 3 h after injection. Blood free fatty acid concentrations were increased, but insulin and glucose levels were unaffected by bGH treatment. In the second study, 54 lactating Holstein cows received i.m. injections of a buffer control solution or recombinant-derived [Met1,Leu127]-bGH, [Ser1,Leu127]-bGH, [Ser1,Val127]-bGH, [delta 1-4,Leu127]-bGH or [delta 1-4,Val127]-bGH. Cows received 25 mg bGH/day for 28 days. The milk response to full-length bGH variants was 6.6 kg/day greater than the response to the amino-terminal deletion variants (P less than 0.05). Substitution of valine for leucine did not affect milk response to either the deletion (delta 1-4) or full-length (Met1 or Ser1) bGH molecules. In conclusion, the lowered galactopoietic potency of pituitary bGH preparations was demonstrated, at least in part, to be due to the presence of amino-terminal amino acid deletions rather than differences in amino acid sequences of recombinant bGH. Ala1 bGH variants with valine at position 127 elicited a greater milk response than Leu127 variants. PMID- 1737959 TI - Release of corticotrophin-releasing factor-41, arginine vasopressin and oxytocin from rat fetal hypothalamic cells in culture: response to activation of intracellular second messengers and to corticosteroids. AB - The effects of the activation of protein kinase A (PKA), protein kinase C (PKC) and corticosteroids were investigated on the release of corticotrophin-releasing factor-41 (CRF), arginine vasopressin (AVP) and oxytocin from rat fetal hypothalamic cells in culture. Both forskolin and PMA (phorbol 12-myristate 13 acetate) increased CRF, AVP and oxytocin release, while dexamethasone and aldosterone only reduced basal secretion of CRF. Both steroids also inhibited forskolin-induced CRF, AVP and oxytocin responses to PMA. These data provide direct evidence for a role for both PKC- and PKA-mediated mechanisms in the regulation of CRF, AVP and oxytocin release and for differential effects of both glucocorticoids and mineralocorticoids on PKA- and PKC-stimulated responses. PMID- 1737960 TI - Effects of cytokines on rat insulinoma INS-1 cells. AB - To investigate further the role of cytokines in the pathogenesis of type I insulin-dependent diabetes mellitus, the effects of interleukin-1 beta (IL-1), tumour necrosis factor-alpha (TNF) and gamma-interferon (IFN) were tested on rat insulinoma INS-1 cells. Whereas TNF and IFN had, respectively, a minor or no effect on insulin production, IL-1 caused a time- and dose-dependent decrease in insulin release and lowered the insulin content as well as the preproinsulin mRNA content of INS-1 cells. Both IL-1 and TNF exerted a cytostatic effect, estimated by a decrease in [3H]thymidine incorporation, while only IL-1 decreased cell viability as measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test. The glutathione content of INS-1 cells was shown to be modulated by the presence of 2-mercaptoethanol in the culture medium, but was not affected by IL-1 or TNF. In conclusion, INS-1 cell culture is considered to be a useful model for studying the effect of cytokines on insulin producing cells. The differentiated features of these cells will permit several questions to be addressed regarding the mechanism of action of IL-1 and eventually other cytokines, both at the level of gene expression and of intracellular signalling. PMID- 1737961 TI - Osmoregulatory adaptation in pregnancy and its disorders. AB - The physiological osmoregulatory adaptations of pregnancy include decreased thresholds for both thirst and AVP secretion and increased MCR for AVP. The combined effects of these changes may unmask subclinical DI. In view of the altered relationship between serum osmolality and thirst, caution is required in investigating thirst and polyuria in pregnancy lest an erroneous diagnosis of psychogenic polydipsia be made. PMID- 1737962 TI - Arachidonic acid-induced LH release is ATP-independent and insensitive to N-ethyl maleimide. AB - The mechanism of arachidonic acid (AA)-induced LH release was characterized using sheep pituitary cells in primary culture permeabilized with Staphylococcal alpha toxin. In intact cells, exogenous AA evoked release of LH in a manner which was partially dependent on extracellular Ca2+. At similar concentrations, AA also caused cell permeabilization as monitored by efflux of [3H]2-deoxyglucose metabolites. In alpha-toxin-permeabilized cells where cytosolic Ca2+ was clamped at resting levels, AA retained its ability to cause LH release. Unlike the stimulation of exocytosis produced by Ca2+, phorbol ester or cyclic AMP, AA evoked release was independent of ATP and was not inhibited by pretreatment with N-ethyl maleimide. These findings indicated that exogenous AA does not cause LH release by Ca2+ influx or mobilization or by activating protein kinase C. The results suggest that LH release induced by exogenous AA is probably due to its detergent-like properties, and does not represent true exocytosis. PMID- 1737963 TI - Expression of an abundant alpha-class glutathione S-transferase in bovine and human adrenal cortex tissues. AB - Bovine adrenal cortex tissue expresses high levels of glutathione S-transferase (GST) from each of the alpha, mu and pi gene families. We describe the purification and characterization of an abundant alpha-class GST from this tissue that has not been identified previously because of its failure to bind to S hexylglutathione-Sepharose 6B (S-hexG-Ag). This enzyme has been affinity purified on glutathione-Sepharose 6B (GSH-Ag) and was obtained in a highly purified form by employing S-hexG-Ag to remove the bulk of GST before chromatography on GSH-Ag. The purified GST eluted from GSH-Ag was found to exhibit marked peroxidase and delta 5-ketosteroid isomerase activities (19.2 and 1.67 U/mg respectively). The bovine enzyme also showed high GST activity towards 4-hydroxynonenal (5.09 U/mg). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that the bovine GST contains two distinct polypeptides, one with an Mr of 25,900 and the other with an Mr of 26,500. An abundant alpha-class GST was also purified from human adrenal cortex that possessed properties which were similar to the bovine alpha-class GST described above; however, unlike the bovine enzyme, the corresponding human alpha-class GST bound to S-hexG-Ag. As with the bovine enzyme, the purified human GST displayed marked peroxidase and isomerase activities (27 and 4.02 U/mg respectively). Further analysis on SDS-PAGE (Mr 25,800) and reverse-phase high-performance liquid chromatography established that this abundant alpha-class GST in human adrenal cortex is equivalent to the human liver GST B1B1 enzyme. As both human and bovine adrenal cortex contain high levels of alpha-class GST with similar catalytic properties, we discuss the possible functions of these enzymes in this tissue. PMID- 1737964 TI - Preferential release of tri-iodothyronine following stimulation by thyrotrophin or thyrotrophin-releasing hormone in sheep of different ages. AB - The influence of TRH and TSH injections on plasma concentrations of tri iodothyronine (T3) and thyroxine (T4) was investigated in neonatal (injection within 0.5 h after delivery) and growing lambs and in normal, pregnant and lactating adult ewes (all 2 years old and originating from Suffolk, Milksheep and Texal crossbreeds). Neonatal lambs had higher levels of T3, T4 and GH compared with all other groups, whereas prolactin and TSH were higher in lactating ewes. In all animals, injections of TRH increased plasma concentrations of prolactin and TSH after 15 min but not of GH at any time. Small increases in T3 and T4 were observed in neonatal lambs, without any effect on the T3 and T4 ratio, after prolactin administration, whereas prolactin did not influence plasma concentrations of T3 or T4 in all other experimental groups. Similar results for thyroid hormones were obtained after TRH or TSH injections. It was therefore concluded that the effects observed after TRH challenge were mediated by the release of TSH. With the possible exception of neonatal lambs, plasma concentrations of T3 after administration of TRH or TSH were always increased before those of T4; the increase in T3 occurred within 0.5-1 h compared with 2-4 h for T4 in all experimental groups. This resulted in an increased ratio of plasma T3 to T4 up to 4 h after injection. It is concluded that, in sheep, TRH and TSH preferentially release T3 from the thyroid gland probably by a stimulatory effect of TSH on the intrathyroidal conversion of T3 to T4. PMID- 1737965 TI - Hyperkeratosis and colposcopy. PMID- 1737966 TI - Streptococci, sore throats, and uncertainty. PMID- 1737967 TI - The effect of aspirin on niacin-induced cutaneous reactions. AB - BACKGROUND: Niacin (nicotinic acid) is one of the first-line agents recommended for the treatment of hyperlipidemia. Bothersome cutaneous reactions (flushing, feeling of warmth, itching, and tingling), however, often limit patient acceptability and tolerability. The National Cholesterol Education Program recommends giving aspirin or another nonsteroidal anti-inflammatory drug before administering niacin. Lack of scientific data supporting this recommendation, however, led to this randomized, double-blind, placebo-controlled trial to evaluate the efficacy of 80 mg of aspirin and 325 mg of aspirin in reducing these cutaneous reactions. METHODS: Thirty-one healthy subjects were randomized into one of four groups. Each group completed four different treatment regimens (placebo-placebo; 80 mg of aspirin-500 mg of niacin; 325 mg of aspirin-500 mg of niacin; and placebo-500 mg of niacin). Subjects received one of each of the four treatment regimens on separate visits that were at least 24 hours apart. Intensity and tolerability of cutaneous reactions were evaluated by an intensity rating scale and a visual analog scale. RESULTS: Results indicate that 325 mg of aspirin is significantly better than 80 mg of aspirin in decreasing intolerability to niacin. Aspirin reduced the incidence of warmth and flushing associated with niacin, but not the itching and tingling. CONCLUSIONS: It appears from this pilot study that preceding niacin with 325 mg of aspirin will decrease the warmth and flushing associated with niacin. PMID- 1737968 TI - Obstetric ultrasound by family physicians. AB - Obstetric ultrasound examination is a useful diagnostic procedure for family physicians who select appropriate equipment, observe indications, understand limitations, and work toward performance mastery. The knowledge obtained during an examination assists clinical decision making and reduces liability. This is particularly true for rural and underserved communities where family physicians provide the majority of prenatal and comprehensive perinatal care. Mastery of obstetric ultrasound techniques can also lead to developing amniocentesis skills and serve as an aid to external cephalic version. The equipment does not require extensive maintenance and is available at all hospitals. Many offices and group practices have found purchase of this equipment to be cost effective. Based on clinical experience in family practice and a review of the medical literature, an approach to skill acquisition and quality assurance is described. PMID- 1737969 TI - Angioedema after long-term enalapril use. AB - A case of life-threatening angioedema occurring after 13 months of enalapril therapy is reported. Clinicians should be aware that such severe reactions can occur, even after long-term therapy. Patients who take angiotensin-converting enzyme inhibitors should be carefully questioned during each follow-up examination concerning angioedema symptoms. PMID- 1737970 TI - A criterion-based review of preventive health care in the elderly. Part 1. Theoretical framework and development of criteria. AB - The magnitude of health care resources devoted to care for the elderly is increasing; however, little is known about the efficacy of the services purchased with those resources. This is especially true in the area of preventive health care. In the absence of a consistent and comprehensive definition of health for the elderly population, it has been difficult either to establish criteria for evaluating preventive services or to assess the impact of those services. This article extends criterion-based review to the assessment of preventive services for the elderly. Health in the elderly can be defined by three related factors: the absence of disease, the maintenance of optimal function, and the presence of an adequate support system. Based on this definition of health, goals for preventive care should include compression of morbidity in addition to prevention of disease, and will require that quality of life be measured to completely assess the value of services. Unfortunately, existing measures of quality of life are difficult to apply to the elderly population, and there are no consistent societal values on which to base a new definition for quality of life. Because existing sets of criteria for the evaluation of preventive services do not address the distinctive health issues affecting the elderly, we have constructed a set of six criteria designed specifically for the well elderly population. In a companion article, we will apply these criteria to candidate preventive services for the elderly population to develop a geriatric health maintenance protocol for use in clinical practice. PMID- 1737971 TI - A new measure of substance abuse treatment. Initial studies of the treatment services review. AB - This paper describes the development and initial testing of the Treatment Services Review (TSR). The TSR is a 5-minute, technician-administered interview that provides a quantitative profile of the number and types of treatment services received by patients during alcohol and drug abuse rehabilitation. Test retest studies indicated satisfactory reliability administered either in person or over the phone. Tests of concurrent validity showed the ability to discriminate different levels of treatment services and good correspondence with independent measures of treatment provided. While additional studies are still needed with this instrument, the data collected thus far suggest that the TSR may serve two types of needs. First, at the programmatic level, the TSR may prove useful in describing and comparing programs in terms of the nature and number of services actually delivered to patients. At the individual patient level, the TSR may offer a means of evaluating the "match" between a patient's needs and the services actually provided. PMID- 1737972 TI - The Harvard Trauma Questionnaire. Validating a cross-cultural instrument for measuring torture, trauma, and posttraumatic stress disorder in Indochinese refugees. AB - There are no valid and reliable cross-cultural instruments capable of measuring torture, trauma, and trauma-related symptoms associated with the DSM-III-R diagnosis of posttraumatic stress disorder (PTSD). Generating such standardized instruments for patients from non-Western cultures involves particular methodological challenges. This study describes the development and validation of three Indochinese versions of the Harvard Trauma Questionnaire (HTQ), a simple and reliable screening instrument that is well received by refugee patients and bicultural staff. It identifies for the first time trauma symptoms related to the Indochinese refugee experience that are associated with PTSD criteria. The HTQ's cultural sensitivity may make it useful for assessing other highly traumatized non-Western populations. PMID- 1737973 TI - Koro epidemics in Guangdong, China. A questionnaire survey. AB - Koro epidemics, characterized by panic due to fear of genital retraction, involving more than 2000 victims, mainly young men, occurred in Hainan Island and Leizhou Peninsula of Guangdong Province, China, in 1984-85 and 1987. A questionnaire survey of 214 victims of these epidemics was conducted in 1988. The survey focused on symptom manifestation, personality profile, life problems, and folk belief. The results of the "koro" group were compared with those of a "clinic" group with minor psychiatric disorder and a "control" group from the non clinical, non-koro episode population in the epidemic area. The results revealed that the victims of the koro epidemics were characterized by low intellectual endowment and strong acceptance of koro-related folk beliefs. The results support the hypotheses that: a) a koro attack is a psychologically induced anxiety-panic condition; b) the presence of an intensive belief in the culturally related concept of koro makes the subject vulnerable to the attack; and c) social crisis or tension serves as a trigger for the occurrence of the epidemic. PMID- 1737974 TI - Behavior of children with seizures. Comparison with norms and effect of seizure type. AB - Scores for 112 children aged 6 to 12 years, with well-controlled seizures and of average or higher IQ, were compared for problem behavior with established norms. As assessed on the Conners' Teacher Rating Scale, the group with seizures was comparable to the normative group on two subscales and superior on two others. In contrast, parents of children in the seizure group rated them as significantly worse on all six subscales of the Revised Behavior Problem Checklist. In a larger group of 133 children with seizures, from which this sample was selected, the relationship of age, sex, and seizure type to behavior problems was examined. Subjects with partial seizures were rated as slightly more aggressive and antisocial than those with generalized seizures. Findings were discussed in regard to differences in perception of behavior by parents and teachers and the possible relevance of seizure type to the expression of behavior problems. PMID- 1737975 TI - Blepharospasm and obsessive-compulsive disorder. AB - Although essential blepharospasm is considered to be a form of focal dystonia, many patients with blepharospasm have been noted to have concomitant depression, anxiety, phobias, hypochondriasis, and other emotional and behavioral disorders, suggesting a psychiatric component to the disease that is phenomenologically similar to obsessive-compulsive disorder (OCD) in terms of the repetitive, perseverative, and persistent nature of the symptoms. The Maudsley OCD questionnaire was administered to 21 patients with blepharospasm and 19 normal controls. The blepharospasm patients scored significantly higher than the controls (p less than .01). Although preliminary, the current study does support at least a phenomenological link between OCD and blepharospasm. PMID- 1737976 TI - Mixed handedness and features of schizotypal personality in a nonclinical sample. AB - Using a nonclinical, noncollege sample, this study set out to confirm and extend previous findings of a relationship between the cognitive-perceptual features of schizotypal personality and mixed handedness using the Schizotypal Personality Questionnaire (SPQ). Based on previous findings of relationships between nondextrality and thought disorder in schizophrenia, it was predicted that the odd speech subscale of the SPQ would have the strongest relationship with mixed handedness. Mixed-handed adults did have significantly higher scores than right handed and left-handed adults on the cognitive-perceptual factor and its subscale of odd speech. Similar trends were also observed for the cognitive-perceptual subscales of suspiciousness, eccentric behavior, and unusual perceptual experiences. These results support and extend previous findings, and are broadly consistent with the association between thought disorder and nondextrality in schizophrenia. PMID- 1737977 TI - Critical importance of stimulus unawareness for the production of subliminal psychodynamic activation effects. An attributional model. AB - This paper describes a new theoretical model of subliminal psychodynamic activation (SPA) effects. The model conceptualizes subliminal-supraliminal differences in SPA effects as being due to differences in subjects' attributions for the changes in anxiety level that are produced by subliminal versus supraliminal SPA stimuli. Changes in anxiety level produced by supraliminal SPA stimuli can be attributed by subjects to the experimental procedures, diminishing the impact of these messages on subjects' responses. In contrast, subjects cannot attribute changes in anxiety level produced by subliminal SPA stimuli to the experimental procedures. Therefore, no "discounting" (i.e., situational) attributions for subliminally induced changes in anxiety levels are available to subjects, and subliminal SPA messages produce significantly stronger effects on responding than do supraliminal SPA messages. The attributional model of SPA effects is discussed in the context of other long-term research programs investigating subliminal phenomena. The implications of this model for clinical treatment and empirical research utilizing the SPA paradigm are discussed. PMID- 1737978 TI - Cognitive bias in the articulated thoughts of depressed and nondepressed psychiatric patients. AB - Beck's cognitive theory of depression postulates several types of cognitive bias among depressed patients. Empirical studies supporting this hypothesis have usually used questionnaire "endorsement" measures of cognition, which may suggest responses to subjects. We used the articulated thoughts during simulated situations (ATSS) method of cognitive assessment in comparing cognitive processes of 15 outpatients with major depression with those of 15 nondepressed psychiatric outpatients in three simulated situations. Depressed patients exceeded nondepressed patients in cognitive bias only in the negative (not the neutral or positive) simulated situation. Discussion centered on the possible utility of ATSS for research on cognition in stressful situations. PMID- 1737979 TI - Microprocesses in perception and personality. AB - This paper utilizes an ontogenetically validated personality test, the Meta Contrast Technique (MCT). The instrument focuses on the microdevelopment of perception (percept genesis) reflecting the process of individual adaptation to and construction of reality. Empirical evidence for the adequacy of the MCT paradigm in neuropsychological personality research is presented. In all, 45 patients were tested; thirty-three patients with various forms of supratentorial brain tumors were examined and compared with a group of 12 cerebrovascular disease (CVD) patients. Without the examiner's knowledge of degree of tumor malignancy, the MCT results allowed differentiation among tumors of various histological types. Uninformed of the final diagnosis, patients with highly malignant gliomas showed panic-related anxiety and schizoid-like regressions, in contrast both to patients with low and nonmalignant brain tumors and to the group of CVD patients. PMID- 1737980 TI - Attention/information-processing factors in psychotic disorders. Replication and extension of recent neuropsychological findings. AB - The scores of attention/information-processing measures derived from neuropsychological testing of 34 chronic psychotic, primarily schizophrenic patients were subjected to a principal components analysis. Measures were chosen a priori on the basis of a previous factor-analytic study by A.F. Mirsky (1987, Behavioral and psychophysiological markers of disordered attention, Environmental Health Perspectives 74:191-199). The factor pattern in the present study was strikingly similar to that reported by Mirsky on a largely nonpsychotic sample. In both studies, four factors emerged that may be identified as: a) perceptual motor speed; b) mental control (numerical-mnemonic); c) flexibility; and d) vigilance. This replication provides support for previously postulated types of attention and suggests that schizophrenic and other psychotic disorders are not associated with atypical organization of attention/information-processing dimensions. The authors discuss questions raised by Mirsky's previous results in light of the present findings. In particular, it was concluded that the flexibility factor requires further clarification. Implications of the findings for clinical evaluation and research in schizophrenia are discussed as well. PMID- 1737981 TI - Disturbances of person identification in Alzheimer's disease. A retrospective study. AB - Person identification disturbances in Alzheimer's disease (AD) add to the suffering of both patients and caregivers. We assessed the prevalence of person identification disturbances in the records of 217 outpatients with AD. These disturbances occurred in 25.4% (N = 55) and included transient misidentifications of familiar persons (N = 34), the Capgras syndrome (N = 11), misidentification of themselves in mirrors (N = 5), prosopagnosia (N = 3), misidentification of unfamiliar persons as familiar (N = 1), and misidentification of another person as oneself (N = 1). Transient misidentifications were easily corrected misperceptions, and the Capgras syndrome and mirror difficulties were associated with suspiciousness/paranoia and delusions. In AD, these findings suggest that misidentifications of familiar persons result from misinterpretations due to cognitive impairments, and the Capgras syndrome and mirror difficulties ensue when these misinterpretations are elaborated by paranoid delusions. PMID- 1737982 TI - On the mechanism of ouabain-induced release of acetylcholine from synaptosomes. AB - Ouabain (5 x 10(-8)-5 x 10(-4) M) was confirmed to cause a dose-dependent increase in [3H]acetylcholine ([3H]ACh) release, cytosolic free Ca2+ concentration ([Ca2+]i), and 22Na+ uptake in cerebrocortical synaptosomes of rats in the presence of extracellular Ca2+. Ouabain also caused a dose-dependent decrease in membrane potential. In a low-Na+ (10 mM) medium, ouabain failed to increase [3H]ACh release and [Ca2+]i. Tetrodotoxin (10(-6) M) had no effect on the ouabain-induced increase in both [3H]ACh release and [Ca2+]i but abolished the increase in 22Na+ uptake and partially inhibited the depolarizing effect. Verapamil (10(-6)-5 x 10(-4) M) inhibited the ouabain-induced increase in both [3H]ACh release and [Ca2+]i in a dose-dependent manner. Removal of extracellular Ca2+ abolished the effect of ouabain on [Ca2+]i but not on [3H]ACh release and 22Na+ uptake, regardless of the presence or absence of EGTA. In the absence of extracellular Ca2+, 10 mM Mg2+ blocked ouabain-induced [3H]ACh release, which was resistant to verapamil. These results suggest that ouabain can increase ACh release from synaptosomes without the preceding increases in intracellular Ca2+ and/or Na+ content. It seems likely that the removal of extracellular Ca2+ unmasks mechanisms of ouabain action different from those operating in the presence of Ca2+. PMID- 1737983 TI - 1-Methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced toxicity in PC12 cells is enhanced by preventing glycolysis. AB - The effects of 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine (2'Et MPTP), 1-methyl-4-(2'-ethylphenyl)pyridinium (2'Et-MPP+), and the classic complex 1 inhibitor, rotenone, on toxicity as well as on rates of glucose use and lactate production were studied using the pheochromocytoma PC12 cell line. PC12 cells are neoplastic in nature and have a high rate of glycolysis accompanied by a large production of lactate and a low use of glucose carbon through the Krebs cycle. 1 Methyl-4-phenylpyridinium (MPP+) and analogues such as 2'Et-MPP+ are actively accumulated by mitochondrial preparations in vitro and block NADH dehydrogenase of complex 1. This blockade results in biochemical sequelae that are ultimately cytotoxic. In this study, untreated PC12 cells used glucose and concomitantly accumulated lactate in a time-dependent manner at all concentrations of glucose studied. Treatment with 50 microM 2'Et-MPP+ or 50 nM rotenone increased both rates significantly, indicating a shift toward increased glycolysis. Cell death caused by the neurotoxins was also time and concentration dependent and markedly enhanced by glucose depletion in the medium. The increase in 2'Et-MPTP-induced toxicity in low glucose-supplemented cells was not due to an increase in pyridinium formation from the tetrahydropyridine, but rather to the lack of glucose for glycolysis. Moreover, inhibition of glycolysis with 2-deoxyglucose or iodoacetic acid also enhanced the lethality of the neurotoxins to the cells. The data in this study provide additional support to the hypothesis that 2'Et-MPP+ or related analogues act to kill cells by inhibiting mitochondrial respiration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737984 TI - Characterization of mono- and polyclonal antibodies against highly purified choline acetyltransferase: a monoclonal antibody shows reactivity in human brain. AB - Choline acetyltransferase (ChAT) from porcine brain was purified by immunoaffinity chromatography, and the highly purified enzyme was subsequently used for immunization of mice and rabbits. After fusion of mouse spleen cells, 32 cultures producing monoclonal antibodies directed against ChAT were detected by an enzyme-linked immunosorbent assay (ELISA) with immunoaffinity-purified ChAT. Of these original 32, the most active 11 cultures were cloned and used for ascites production. The 11 clones generated monoclonal antibodies of the immunoglobulin (Ig) M class (three), the IgG1 subclass (seven), and the IgG2b subclass (one). The isoelectric points of the antibodies of the IgG class were different in each case. The monoclonal antibodies exhibited different binding characteristics in the above ELISA and on western blots. Two monoclonal antibodies demonstrated excellent immunohistological results with neurons of rat brain and spinal cord. One of them reacted well immunohistochemically with neurons of human brain and also recognized partially purified human placenta ChAT in the ELISA. PMID- 1737986 TI - Bicuculline- and baclofen-insensitive gamma-aminobutyric acid binding to rat cerebellar membranes. AB - Up to 60% of gamma-[3H]aminobutyric acid ([3H]GABA) bound specifically to rat cerebellar membranes in the absence of Ca2+ was insensitive to the GABAA antagonist bicuculline and to the GABAB agonist baclofen. This indicates that a significant component of specifically bound [3H]GABA is associated with non GABAA, non-GABAB binding sites. The presence of this binding component appeared seasonal, peaking in the month of September (early spring) each year over a 4 year period. The calcium independence and bicuculline and baclofen insensitivity of the binding indicate that this binding is not to the classical GABAA and GABAB binding sites. High concentrations of muscimol and isoguvacine inhibited non GABAA, non-GABAB binding. Scatchard analysis of the non-GABAA, non-GABAB binding sites indicated two kinetic components: KD1 = 42 nM and KD2 = 9.2 microM; Bmax1 = 1.6 pmol/mg of protein and Bmax2 = 28 pmol/mg of protein. PMID- 1737985 TI - Tumor necrosis factor modulates the inactivation of catecholamine secretion in cultured sympathetic neurons. AB - Cytokines exert multiple effects on cellular functions. We studied the effects of cytokines on the calcium-dependent release of catecholamines in cultured neurons from neonatal rat superior cervical ganglia. Incubation of sympathetic neurons with recombinant human interleukin-1 beta (0.14-0.7 nM) or recombinant human tumor necrosis factor-alpha (1 nM) for 24-48 h had no effect on the baseline spontaneous release and the initial K(+)-evoked [3H]norepinephrine release, compared with untreated cells. A repeat K(+)-induced depolarization after 6 min resulted in a decrease of [3H]norepinephrine secretion to 69 +/- 5.8% (n = 11) of the initial secretion in recombinant human tumor necrosis factor-treated cells, but not in control cells. The secretory response was restored when the interval between the two K+ challenges was increased to 10 min. We conclude that the diminished secretory response to a repeat stimulus in recombinant human tumor necrosis factor-treated superior cervical ganglia neurons is due to a prolonged recovery from inactivation of secretion in these cells. PMID- 1737987 TI - Isolation and identification of methylarginines from bovine brain. AB - Methylarginines in free form were identified in bovine brain. Three compounds were isolated from the basic aliphatic amino acid fraction of bovine brain with several ion-exchange chromatographies. They showed the same Rf values in paper and thin-layer chromatographies as those of authentic NG-monomethylarginine, NG,NG-dimethylarginine, and NG,N'G-dimethylarginine. The migration distance of the isolated compounds in high-voltage paper electrophoresis and the retention times in ion-exchange HPLC were also identical to those of the above authentic methylarginines. We concluded that these three compounds are the methyl derivatives of arginine described above. The amount of these three compounds isolated from 1,090 g of bovine brain was 0.3 mumol of NG-monomethylarginine, 0.1 mumol of NG,NG-dimethylarginine, and 0.5 mumol of NG,N'G-dimethylarginine. The occurrence of these free methylarginines may have an important role in regulating the signal transduction through the nitric oxide system. PMID- 1737988 TI - Bradykinin stimulates arachidonic acid release through the sequential actions of an sn-1 diacylglycerol lipase and a monoacylglycerol lipase. AB - In cultured dorsal root ganglion (DRG) neurons prelabeled with [3H]arachidonic acid [( 3H]AA), bradykinin (BK) stimulation resulted in increased levels of radioactive diacylglycerol, monoacylglycerol, and free AA. The transient increases in content of radioactive diacylglycerol and monoacylglycerol preceded the increase in level of free AA, suggesting the contribution of a diacylglycerol lipase pathway to AA release. An analysis of the molecular species of diacylglycerols in unstimulated cultures revealed the presence of two primary [3H]AA-containing species, 1-palmitoyl-2-arachidonoyl and 1-stearoyl-2 arachidonoyl diacylglycerol. BK stimulation resulted in a preferential increase in content of 1-stearoyl-2-arachidonoyl diacylglycerol. When DRG cultures were labeled with [3H]stearic acid, treatment with BK increased the amount of label in diacylglycerol and free stearic acid, but not in monoacylglycerol. This result suggested that AA release occurred through the successive actions of an sn-1 diacylglycerol lipase and monoacylglycerol lipase. Other data supporting a diacylglycerol lipase pathway was the significant inhibition of [3H]AA release and consequent accumulation of diacylglycerol by RG 80267, which preferentially inhibits diacylglycerol lipase. Analysis of the molecular species profiles of individual phospholipids in DRG neurons indicated that phosphoinositide hydrolysis may account for a significant portion of the rapid increase in content of 1-stearoyl-2-arachidonoyl diacylglycerol. We were unable to obtain evidence that the phospholipase A2 pathway makes a significant contribution to BK stimulated AA release in DRG cultures. Under our assay conditions there were no BK-stimulated increases in levels of radioactive lysophosphatidylinositol, lysophosphatidylcholine, or lysophosphatidylethanolamine in cultures prelabeled with [3H]inositol, [3H]choline, or [3H]-ethanolamine, respectively. PMID- 1737989 TI - Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein. AB - Most cells possess a variety of mechanisms, such as high levels of glutathione, that guard against cytotoxic free radicals, which are suspected in the etiology of various neurological deficits. Neurons, however, are deficient in this antioxidant source. The list of other potent antioxidants includes the bile pigments biliverdin and bilirubin. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2, catalyze the rate-limiting step in the only biological pathway by which bile pigments are produced. In this study, heat shock is identified as the only stimulus reported to date that can alter expression in brain HO-1 of protein and mRNA in vivo. Using a HO-1 cDNA probe, we examined the level of HO-1 mRNA in normal rat brain and in brain 1 and 6 h following heat shock. Exposure of male rats to 42 degrees C for 20 min caused a 20-fold increase in brain HO-1 1.8-kb mRNA within 1 h after treatment. Quantification of brain HO-1 protein by HO-1 radioimmunoassay revealed a fourfold increase at 6 h posttreatment. In normal brain, HO-1 protein was sparsely expressed in few select neuronal and nonneuronal cell populations in forebrain, diencephalon, cerebellum, and brainstem regions. Six hours following heat shock, an intense increase in HO-1 protein in glia throughout the brain, ependyma lining the ventricles of the brain, paraventricular nucleus, Purkinje cell layer of the cerebellum, and cochlear nucleus of brainstem was observed. We suggest that increases in HO-1 transcript and protein reflect a means to elevate levels of antioxidants in cells with compromised defense mechanisms caused by stress. PMID- 1737990 TI - DM-20 mRNA is expressed during the embryonic development of the nervous system of the mouse. AB - We used both the polymerase chain reaction (PCR) and in situ hybridization to search for the presence of proteolipid protein (PLP) gene transcripts in the developing mouse. Total brain RNA extracted from 13-19-day embryos, analyzed by PCR, demonstrated the presence of a single transcript that was unambiguously identified with the DM-20 mRNA. RNA samples from postnatal day 2 animals also showed a signal corresponding to the PLP transcript, in addition to the DM-20 message. By in situ hybridization of 10-day embryos using a DM-20 antisense cRNA probe, we showed that the localization of the DM-20 message was restricted to the diencephalic basal plate. On the same embryo sections, in addition to the brain localization, an intense hybridizing signal was also detected in the trigeminal and spinal ganglia, the vagal glossopharyngeal ganglion, and the sympathetic ganglion chain. The demonstration of transcription of the PLP gene, long before the beginning of the myelination process, suggests that in addition to a structural function in myelin compaction, some of the products of the PLP gene (DM-20) may have a role during the compartmentalization and differentiation of the neural tube. PMID- 1737991 TI - Kinetic analysis of the chloride dependence of the neuronal uptake of dopamine and effect of anions on the ability of substrates to compete with the binding of the dopamine uptake inhibitor GBR 12783. AB - The specific binding of [3H]1-[2-(diphenyl-methoxy)ethyl]-4-(3-phenyl-2 propenyl)piperazine ([3H]GBR 12783) to the dopamine (DA) neuronal carrier present in membranes prepared from rat striatum was not affected when Cl- was replaced by either Br- or NO3-. In media containing Cl-, Br-, or NO3-, d-amphetamine and DA competed with the radioligand in a monophasic manner with Hill coefficients of close to 1 (0.94-1.12). Replacement of Cl- by Br- impaired the ability of some substrates (d-amphetamine, DA, p-hydroxyamphetamine, and m-tyramine) to compete with [3H]GBR 12783. The potency of Br- to decrease the affinity of substrates for the specific binding site was significantly correlated (t = 7.07, p less than 0.001) with their affinity for this binding site. These results suggest that the various substrates tested could bind to recognition sites in which Cl- is differently involved; as a consequence, substrates could bind to the neuronal carrier by means of partly different links. In experiments dealing with the specific uptake of [3H]DA, F-, NO3-, isethionate-, or acetate- was unable to substitute for Cl-, whereas Br- was quite a total substitute. Replacement of Cl- by equimolar concentrations of either NO3- or isethionate- resulted in inhibition curves of DA specific uptake with Hill coefficients of close to 1 (0.77 and 1.04 respectively); this indicates that both NO3- and isethionate- are devoid of inhibitory effects on neuronal uptake and are quite ineffective substitutes for Cl-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1737992 TI - Vesamicol binding to subcellular membranes that are distinct from catecholaminergic vesicles in PC12 cells. AB - We have examined PC12 cells for the localization of binding sites for vesamicol [l-2-(4-phenylpiperidino) cyclohexanol], a compound that has previously been shown to bind to cholinergic vesicles and to inhibit the uptake of acetylcholine. Initial studies presented in this article demonstrate the existence of a specific, saturable vesamicol binding site in PC12 cells. Subsequent experiments show that these binding sites reside in a membrane population that is distinct from catecholamine-containing compartments with respect to density and antigenic composition. In particular, vesamicol binding compartments have a lower density than catecholaminergic vesicles and, unlike these latter vesicles, do not appear to contain the vesicle-specific proteins synaptophysin and SV2 as part of the same membrane. These results suggest that vesicular transport proteins for acetylcholine and catecholamines are differentially sorted to distinct membrane compartments in PC12 cells. PMID- 1737993 TI - Rat hippocampal lactate efflux during electroconvulsive shock or stress is differently dependent on entorhinal cortex and adrenal integrity. AB - The role of the entorhinal cortex and the adrenal gland in rat hippocampal lactate formation was assessed during and after a short-lasting immobilization stress and electroconvulsive shock (ECS). Extracellular lactate was measured on line using microdialysis and enzyme reactions (a technique named lactography); in some rats, unilateral lesions of the entorhinal cortex were made or the bilateral adrenal glands were removed. The stress-evoked increase in hippocampus lactate was not altered either ipsi- or contralateral to an entorhinal cortex lesion. The response to ECS was attenuated only in the hippocampus ipsilateral to the entorhinal cortex lesion. Removal of bilateral adrenal glands caused some delay in the increase in hippocampal lactate after ECS and a major reduction in the stress-evoked lactate response. These results indicate that (1) the entorhinal cortex is activated by ECS, thereby activating hippocampal lactate efflux and presumably metabolism, and (2) the adrenal gland is essential in the response to stress and, to a minor extent, in the ECS-altered hippocampal metabolism. PMID- 1737994 TI - Nuclear magnetic resonance spectroscopy study on energy metabolism, intracellular pH, and free Mg2+ concentration in the brain of transgenic mice overexpressing human ornithine decarboxylase gene. AB - We have generated a transgenic mouse line strikingly overexpressing the human ornithine decarboxylase (ODC) gene in their brain. Brain ODC activity was increased in the transgenic animals by a factor of 70 in comparison with their nontransgenic littermates. The content of brain putrescine, the product of ODC, was greater than 60 mumol/g of tissue in the transgenic mice, whereas in the normal animals it was below the level that could be detected by an HPLC method. The concentrations of the higher polyamines (spermidine and spermine) were not significantly different from control values. 31P nuclear magnetic resonance (31P NMR) spectroscopy analyses revealed a significantly reduced (40%) free Mg2+ concentration as calculated from the chemical shift differences of the nucleoside triphosphate alpha and beta peaks in the brains of the transgenic animals. The lower free Mg2+ concentration in the brains of ODC transgenic mice was not a consequence of altered intracellular pH or changes in cellular high-energy metabolites. 1H NMR showed no differences in brain choline/N-acetylaspartate and total creatine/N-acetylaspartate ratios between the two animal groups. These ODC transgenic animals may serve as models in vivo for studies on cerebral postischemic events and on epilepsy, as polyamines are supposed to be involved in these processes. PMID- 1737995 TI - Uptake and metabolism of choline by rat brain after acute choline administration. AB - The present study is concerned with the uptake and metabolism of choline by the rat brain. Intraperitoneal administration of choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of choline across the brain to positive values at plasma choline levels of greater than 23 microM. Net choline release and uptake were linearly dependent on the plasma choline level in the physiological range of 10-50 microM, whereas the CSF choline level was significantly increased only at plasma choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]choline chloride caused the net uptake of greater than 500 nmol/g of choline by the brain as calculated from the AVD, which was reflected in a minor increase of free choline level and a long-lasting increase of brain phosphorylcholine content, which paralleled the uptake curve. Loss of label from phosphorylcholine 30 min to 24 h after choline administration was accompanied by an increase of label in phosphatidylcholine, an indication of a delayed transfer of newly taken-up choline into membrane choline pools. In conclusion, homeostasis of brain choline is maintained by a complex system that interrelates choline net movements into and out of the brain and choline incorporation into and release from phospholipids. PMID- 1737996 TI - Reserpine-induced processing of chromogranin A in cultured bovine adrenal chromaffin cells. AB - The effect of reserpine on the processing of the secretory granule protein chromogranin A (CgA) in isolated bovine adrenal chromaffin cells was investigated using two radioimmunoassays employing site-specific antisera. The two antisera were directed against closely associated regions of the CgA molecule which would be exposed by specific processing: antiserum L331 was raised against the C terminus of the regulatory peptide pancreastatin, and the second antiserum, L300, was raised against the synthetic peptide [Tyr0]CgA306-313 (YLSKEWEDA), a sequence that lies immediately C-terminal to pancreastatin and adjacent to a dibasic amino acid cleavage site. Chronic reserpine treatment of chromaffin cells produced a time- and dose-dependent increase in processing, as demonstrated by an increase in pancreastatin- and YLSKEWEDA-immunoreactivity (ir). The reserpine-induced rise in pancreastatin-ir was due predominantly to an increase in pancreastatin 1-47, whereas the rise in YLSKEWEDA-ir was due to increases in three polypeptides: a 51 kDa YLSKEWEDA-ir polypeptide, CgA297-313, and CgA248-313. The latter predominated. The action of reserpine on both pancreastatin- and YLSKEWEDA-ir was found to be largely inhibited by the protein synthesis inhibitor cycloheximide. The results show that treatment of isolated chromaffin cells with reserpine induces both the selective proteolytic processing and peptidyl-glycine amidation of CgA and its derived fragments. As reserpine has a similar effect on proenkephalin in chromaffin cells, the results suggest that reserpine induces a general increase in the activity of the processing enzymes, partially by an increase in protein synthesis. PMID- 1737997 TI - A highly sensitive assay for histamine using ion-pair HPLC coupled with postcolumn fluorescent derivatization: its application to biological specimens. AB - A simple and highly sensitive method for the determination of histamine (HA) was developed using ion-pair, reversed-phase HPLC coupled with postcolumn o phthalaldehyde derivatization fluorometry, and it was applied to the unpurified extracts of human and rat plasma, and brains of rats and mice. The HA concentrations both in the plasma and brains determined by the present method were well consistent with the values obtained by cation-exchange HPLC with postcolumn fluorescent derivatization currently in use. The present method was more advantageous than the assay using cation-exchange HPLC: (1) it was three to four times more sensitive (the detection limit was 0.5 pg of HA), and (2) it enabled the measurement of HA in samples containing (R)alpha-methylhistamine, a potent and specific H3-receptor agonist, which could not be separated from HA by cation-exchange chromatography. Using the present method coupled with intracerebral microdialysis, we found in the rat hypothalamus that (R)alpha methylhistamine (5 mg/kg i.p.) markedly decreased the extracellular concentration of HA with a maximal effect (83% reduction) during 30-60 min after injection, suggesting that most of HA in the microdialysate fraction is neuronal in origin. PMID- 1737998 TI - Brain transfer coefficients for 67Ga: comparison to 55Fe and effect of calcium deficiency. AB - The transfer coefficients (Kin) for the uptake of gallium-67 (67Ga) into brain and CSF were determined in unanesthetized male Fischer-344 rats fed either a normal or a low-Ca diet. Kin for 67Ga was also compared with transfer coefficients for the uptake of iron-55 (55Fe) and 125I-albumin in control animals. The value of CSF 67Ga Kin was 3 x 10(-7) ml.g-1.s-1 and was 50% larger in low-Ca animals. Brain regional Kin values for 67Ga were 3-9 x 10(-7) ml.g-1.s 1 with no differences in Kin between normal and low-Ca rats. CSF Kin values for 55Fe were 40% and those for albumin were 15% of Kin for 67Ga. For brain, Kin values for 55Fe were 15-40% smaller than for 67Ga, but for albumin the Kin values were 85% less than for 67Ga. 67Ga was found to be 99% bound to plasma proteins, whereas 55Fe was 99.9% bound. The results indicate that metals that are primarily bound to transferrin enter the CSF and brain very slowly. Uptake of both metals was faster than albumin, which may indicate that metal bound to small chelates contributes significantly to brain uptake. In addition, Ca deficiency does not enhance entry of Ga into the brain. PMID- 1737999 TI - Dissimilar aluminum and gallium permeation of the blood-brain barrier demonstrated by in vivo microdialysis. AB - Aluminum (Al) and gallium (Ga) permeations of the blood-brain barrier (BBB) were assessed in rats. Unbound extracellular Al and Ga concentrations were ascertained at the two potential sites of BBB permeation, cerebral capillaries and choroid plexuses, by implantation of microdialysis probes in the frontal cortex and lateral ventricle, respectively. A microdialysis probe implanted in the jugular vein revealed unbound blood Al or Ga concentrations. Al or 67Ga citrate was administered via the femoral vein. Peak Al and Ga concentrations were seen within the first 10 min at all three sites. Area under the curve (concentration vs. time to final sample) values were calculated using RSTRIP. Within-rat overall frontal cortical/blood and lateral ventricular/blood ratios [brain/blood ratios (oBBRs)] were calculated from area under the curve values. Aluminum frontal cortical oBBRs were significantly higher than those for the lateral ventricle. Ga oBBRs were not significantly different between the two sites. Al and Ga oBBRs were significantly different in the lateral ventricle. These results suggest that the primary site of A1 permeation across the BBB is at cerebral capillaries, whereas Ga permeation across the BBB does not significantly differ between cerebral capillaries and choroid plexuses. The use of Ga as a model to study Al pharmacokinetics may not be appropriate in the elucidation of the site or mechanism of Al entry into the brain. PMID- 1738000 TI - Quantitative examination of tissue concentration profiles associated with microdialysis. AB - Spatial solute concentration profiles resulting from in vivo microdialysis were measured in rat caudate-putamen by quantitative autoradiography. Radiolabeled sucrose was included in the dialysate, and the tissue concentration profile measured after infusions of 14 min and 61.5 min in an acute preparation. In addition, the changes in sucrose extraction fraction over time were followed in vivo and in a simple in vitro system consisting of 0.5% agarose. These experimental results were then compared with mathematical simulations of microdialysis in vitro and in vivo. Simulations of in vitro microdialysis agreed well with experimental results. In vivo, the autoradiograms of the tissue concentration profiles showed clear evidence of substantial differences between 14 and 61.5 min, even though the change in extraction fraction was relatively small over that period. Comparison with simulated results showed that the model substantially underpredicted the observed extraction fraction and overall amount of sucrose in the tissue. A sensitivity analysis of the various model parameters suggested a tissue extracellular volume fraction of approximately 40% following probe implantation. We conclude that the injury from probe insertion initially causes disruption of the blood-brain barrier in the vicinity of the probe, and this disruption leads to an influx of water and plasma constituents, causing a vasogenic edema. PMID- 1738001 TI - Magnesium-dependent enhancement of endogenous agonist binding to A1 adenosine receptors: a complicating factor in quantitative autoradiography. AB - Quantitative autoradiography was used to investigate the effects of Mg2+ on agonist and antagonist binding to A1 receptors in rat striatum. A1 receptors were labelled with the selective agonist N6-[3H]cyclohexyladenosine ([3H]CHA) or the selective antagonist 1,3-[3H]dipropyl-8-cyclopentylxanthine ([3H]DPCPX). Mg2+ had no significant effect on equilibrium binding constants for [3H]CHA [control: KD (95% confidence interval) of 0.34 (0.15-0.80) nM and Bmax of 267 +/- 8 fmol/mg of gray matter; with 10 mM Mg2+: KD of 0.8 (0.13-4.9) nM and Bmax of 313 +/- 8.9 fmol/mg of gray matter] or [3H]DPCPX [control: KD of 0.54 (0.30-0.99) nM and Bmax of 256 +/- 2.3 fmol/mg of gray matter; with 10 mM Mg2+: KD of 1.54 (0.2-11.0) nM and Bmax of 269 +/- 35.7 fmol/mg of gray matter]. In contrast, Mg2+ slowed the apparent association rate for both ligands; this was observed as a shift from a one-component to a two-component model for [3H]DPCPX. Mg2+ also affected the dissociation rates of both ligands; for [3H]CHA, dissociation in the presence of Mg2+ was not detected. Mg2+ produced a concentration-dependent inhibition of [3H]CHA binding only prior to equilibrium. HPLC was performed on untreated sections, sections preincubated with adenosine deaminase (ADA), and sections preincubated with ADA and incubated with ADA in the absence or presence of Mg2+. Adenosine was found in measurable quantities under all conditions, and the concentration was not influenced by Mg2+ or by the inclusion of GTP in the preincubation medium. From these data, we conclude the following: (a) adenosine is present and may be produced continuously in brain sections; (b) ADA is not capable of completely eliminating the produced adenosine; (c) Mg2+ apparently does not influence adenosine production or elimination; (d) A1 receptor-guanine nucleotide binding protein coupling is maximal in this preparation; and (e) Mg2+ decreases the dissociation rate of bound endogenous adenosine from A1 receptors, thus limiting the access of [3H]CHA and [3H]DPCPX to the receptors. Thus, enhancement of endogenous adenosine binding to A1 receptors by Mg2+ is a complicating factor in receptor autoradiography and may be so in other preparations as well. PMID- 1738002 TI - Biochemical and pharmacological characterization of serotonin-O carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites. AB - There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin-1B (5-HT1B) and serotonin-1D (5-HT1D) binding sites. Serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S-CM G[125I]TNH2-binding sites were studied by quantitative autoradiography on rat and guinea pig brain sections. S-CM-G[125I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5-HT1B sites in the rat and of 5-HT1D sites in the guinea pig. The binding of 0.02 nM S-CM-G[125I]TNH2 was inhibited by low concentrations of 5-HT, S-CM-GTNH2, CGS 12066 B, 5 methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin inhibited S-CM-G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5-HT1C, 5-HT2, 5-HT3, and adrenergic receptors, inhibited S-CM-G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S-CM-G[125I]TNH2 is then a useful new probe for the direct study of 5-HT1B and 5-HT1D binding sites. PMID- 1738003 TI - Detection of mobile proteins by proton nuclear magnetic resonance spectroscopy in the guinea pig brain ex vivo and their partial purification. AB - Proton nuclear magnetic resonance (1H NMR) spectroscopy was used to study metabolites of the brain cortex ex vivo. The superfused brain cortex preparation was judged to be metabolically viable on the basis of the 31P NMR spectrum (intracellular pH of 7.23 +/- 0.03 and phosphocreatine/ATP ratio of 1.21 +/- 0.09). Using 1H NMR a group of previously unidentified signals was detectable at 0.94, 1.22, and 1.40 ppm with a water-suppressed spin-echo sequence. These signals had shorter spin-spin relaxation times (51-54 ms) than N-acetylaspartate and lactate (84-93 ms) and also smaller saturation factors, an indication of shorter spin-lattice relaxation times than the latter two low-molecular-weight metabolites. The unidentified signals also displayed homonuclear coupling to other spins in the methine region of the spectrum. Acid extraction of the brain slices or cortex from animals that were killed yielded a mixture of proteins that exhibited NMR properties matching the 1H NMR signals in the brain cortex. The molecular mass of these thermoresistant, "mobile" proteins, which contained proline plus hydroxyproline (9-16% of all amino acids), ranged between 8 and 40 kDa. These "new" assignments of 1H NMR-detectable compounds may influence interpretation of NMR data of some metabolites, as their signals are in the vicinity of the -CH3 1H NMR peaks of lactate and alanine. PMID- 1738004 TI - Characterization of neutral proteinases from Alzheimer-affected and control brain specimens: identification of calcium-dependent metalloproteinases from the hippocampus. AB - Three neutral proteinases from human hippocampal tissue have been identified and partially characterized using substrate gel electrophoresis. The proteinases showed activity when gelatin was used as the substrate, but had no detectable activity against casein. Based on the results of inhibition studies and the calcium requirements, it was concluded that the activities were due to calcium dependent metalloproteinases. The apparent molecular weights were 130,000 (MP 130), 100,000 (MP-100), and 70,000 (MP-70). Half-maximal activities were observed with 20 microM Ca2+ for MP-130, 40 microM Ca2+ for MP-100, and 800 microM Ca2+ for MP-70. In the presence of Ca2+, Zn2+ reestablished the activities of the three metalloproteinases at a lower concentration than did either Co2+ or Mn2+. One millimolar Al3+ inhibited 67% of the MP-70 activity, but did not affect the MP-100 and MP-130 activities. An analysis of Alzheimer-affected hippocampal and control samples showed that the specific activity (in units per milligram of sodium dodecyl sulfate-soluble protein) of MP-70 varied less than the activities of MP-100 and MP-130 between the two groups. Although p-amino-phenylmercuric acetate (p-APMA) increased the activities of MP-70 by 70% in both groups of specimens, the resulting activities from Alzheimer samples were greater than those from control samples (p less than 0.01). A wide range of MP-100 specific activity was observed in both groups, and its mean activity was higher in Alzheimer-affected samples (p less than 0.05). Treatment with p-APMA increased the activity of MP-100 only 25% in both groups of tissue samples. MP-130 activity was detected predominantly in Alzheimer-affected hippocampal specimens, and treatment with p-APMA failed to increase its activity in both the control and the Alzheimer-affected specimens. The results demonstrate an elevated level of metalloproteinase activities, capable of degrading tissue matrix components, in the hippocampus from postmortem Alzheimer patients. PMID- 1738005 TI - Synapses on motoneuron dendrites in the brachial section of the frog spinal cord: a computer-aided electron microscopic study of cobalt-filled cells. AB - Cobalt-labelled motoneuron dendrites of the frog spinal cord at the level of the second spinal nerve were photographed in the electron microscope from long series of ultrathin sections. Three-dimensional computer reconstructions of 120 dendrite segments were analysed. The samples were taken from two locations: proximal to cell body and distal, as defined in a transverse plane of the spinal cord. The dendrites showed highly irregular outlines with many 1-2 microns-long 'thorns' (on average 8.5 thorns per 100 microns 2 of dendritic area). Taken together, the reconstructed dendrite segments from the proximal sites had a total length of about 250 microns; those from the distal locations, 180 microns. On all segments together there were 699 synapses. Nine percent of the synapses were on thorns, and many more close to their base on the dendritic shaft. The synapses were classified in four groups. One third of the synapses were asymmetric with spherical vesicles; one half were symmetric with spherical vesicles; and one tenth were symmetric with flattened vesicles. A fourth, small class of asymmetric synapses had dense-core vesicles. The area of the active zones was large for the asymmetric synapses (median value 0.20 microns 2), and small for the symmetric ones (median value 0.10 microns 2), and the difference was significant. On average, the areas of the active zones of the synapses on thin dendrites were larger than those of synapses on large calibre dendrites. About every 4 microns 2 of dendritic area received one contact. There was a significant difference between the areas of the active zones of the synapses at the two locations. Moreover, the number per unit dendritic length was correlated with dendrite calibre. On average, the active zones covered more than 4% of the dendritic area; this value for thin dendrites was about twice as large as that of large calibre dendrites. We suggest that the larger active zones and the larger synaptic coverage of the thin dendrites compensate for the longer electrotonic distance of these synapses from the soma. PMID- 1738006 TI - The logistic modeling of sensitivity, specificity, and predictive value of a diagnostic test. AB - A method is described for modeling the sensitivity, specificity, and positive and negative predictive values of a diagnostic test. To model sensitivity and specificity, the dependent variable (Y) is defined to be the dichotomous results of the screening test, and the presence or absence of disease, as defined by the "gold standard", is included as a binary explanatory variable (X1), along with variables used to define the subgroups of interest. The sensitivity of the screening test may then be estimated using logistic regression procedures. Modeled estimates of the specificity and predictive values of the screening test may be similarly derived. Using data from a population-based study of peripheral arterial disease, the authors demonstrated empirically that this method may be useful for obtaining smoothed estimates of sensitivity, specificity, and predictive values. As an extension of this method, an approach to the modeling of the relative sensitivity of two screening tests is described, using data from a study of screening procedures for colorectal disease as an example. PMID- 1738007 TI - The "Intervention Index": insufficient information. PMID- 1738008 TI - Ischemic heart disease prevention: estimating the impact of interventions. AB - The potential impact of ischemic heart disease intervention programs has usually been assessed using the dichotomy between those programs targeted to high risk groups and those that are population based, but this distinction does not adequately describe the spectrum of possibilities. Using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS), we assessed the effect of a spectrum of 27 potential interventions on mortality reduction and on an Intervention Index (defined as the number of persons whose risk must change to prevent one death). Using combinations of cholesterol reductions of 20% and decreases in the prevalence of smoking and hypertension of 50%, reductions in mortality varied from 1 to 27% and the Intervention Index varied from 26 to 520. A number of potential interventions were equivalent in their mortality reduction of their Intervention Indexes, despite their affecting differing proportions of the population. The Intervention Index provides some measure of the relative efficiency of programs and points to the comparability of different interventive approaches. In addition, this analysis suggests that the potential impact of intervention programs on mortality will be modest, but that a focus on certain subgroups, such as those aged 40-59 years, can achieve substantial results within those groups, even though the population effect would be minimal. PMID- 1738009 TI - A randomized controlled trial of dietary fat reduction: the retention of subjects and characteristics of drop outs. AB - We have examined the feasibility of carrying out a randomized controlled trial of dietary fat reduction in women at increased risk for breast cancer. The randomization was either to a control group who were taught the principles of balanced nutrition, but were not counselled to change their fat intake, or to an intervention group who were taught to reduce their dietary fat intake to 15% of total calories from a baseline average of 35% of calories. Potentially eligible subjects were women attending a breast diagnostic clinic who had the mammographic pattern of dysplasia. Subjects were recruited by letter from their referring surgeon followed by a telephone call. Subjects interested in participating in the study then entered by one of two phases. In Phase I, the study was explained, informed consent sought and willing subjects randomized to the intervention or control group. Using this procedure 227 subjects were randomized and 48 (21%) dropped out of the study in the 12 months following randomization. (A drop out was defined as a subject who persistently failed to keep appointments and provide nutrient data.) Of these drop outs, 30 (63%) occurred at or soon after randomization. A modified procedure of entry was then adopted in which subjects interested in the study were first taught the procedures involved, including keeping food records and clinic appointments, and were then asked to provide consent and randomized. Two hundred and eighty subjects were enrolled using this modified procedure and 25 (9%) have dropped out in the 12 months following randomization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738010 TI - Relationships of site of infarction and history of previous infarction with short and long-term prognosis after acute myocardial infarction in Japan. AB - We studied the outcome in 308 patients with acute myocardial infarction (MI) admitted to the coronary care unit of Kobe General Hospital. Short-term outcome (within 28 days after MI) and long-term outcome (more than 28 days) were examined with survival curves to find any relationship with a history of previous MI and with the site of the MI. In the short term, 38 of the 308 patients died of cardiac causes. The group with anterior MI tended to have higher mortality than the group of patients with inferior MI, and among patients without a previous MI, patients with anterior MI had significantly higher mortality (p = 0.01). In multivariate analysis by the logistic regression model, the site of the MI was found to be independently associated with the short-term outcome. In the long term, with a mean follow-up of 3.4 years, 23 of the 308 patients died of cardiac causes. Different sites of the MI did not result in different outcomes in patients with or without a previous MI. Of patients with anterior or inferior MI, those with a previous MI tended to have higher mortality, and of patients with an inferior MI, the difference was significant (p = 0.001). In multivariate analysis by the proportional hazards model, a history of MI was more predictive than the site of the MI. In conclusion, the site of the MI was associated more with the short-term outcome than with the long-term outcome, and a history of MI was associated more closely with the long-term outcome. PMID- 1738011 TI - Prognosis in long-term immunosuppressive treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy. AB - Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) frequently includes use of immunosuppressive agents. Controlled treatment trials demonstrating efficacy are available only for prednisone and therapeutic plasma exchange (TPE). When these fail to achieve lasting chemical improvement after reduction or cessation of therapy, subsequent regimens are empiric, often leading to prolonged immunosuppression. It is not possible to predict who will respond to which agent and when. Administered individually, immunosuppressive agents may pose an acceptable risk, but cumulative effects of multiple agents in refractory patients may suppress the immune system and contribute to increased morbidity and mortality. Treatment difficulties with refractory CIDP patients have not been emphasized, and long-term effects of immunosuppression have focused on the risk of malignancy. In reviewing our clinical experience treating over 100 CIDP patients we identified approximately 20 patients who could be considered refractory to multiple immunosuppressive therapies and dependent upon long-term intermittent TPE. Two of these patients exemplify the morbidity associated with CIDP and its associated treatment. Our review of the clinical course of these patients raised issues about the use of multiple immunosuppressive agents, long term goals, and long-term prognosis in CIDP. PMID- 1738012 TI - An analysis of symptoms in patients with permanent ventricular pacemakers. AB - The prevalence and severity of symptoms of the "pacemaker syndrome" were investigated in 64 patients with VVI pacemakers and compared, in the same patients, to a series of control symptoms, unrelated to pacemaker function. Symptoms were also compared in patient groups unlikely to have the "pacemaker syndrome" (atrial fibrillation), most likely to have such symptoms (retrograde atrial activation) and in an intermediate group (competitive paced and sinus rhythms). There was a linear relationship between the frequency and severity of "pacemaker" symptoms and control questions in all groups and no preponderance of "pacemaker" symptoms in any group. The study provides an estimate of the number and severity of symptoms in patients with VVI pacemakers, demonstrates the non specificity of the "pacemaker syndrome" and shows no evidence of a sub-clinical "pacemaker syndrome" in the patients observed. PMID- 1738013 TI - The psychological and physical health of family members caring for an elderly person with dementia. AB - Most elderly persons with dementia are cared for at home, usually by the spouse or an adult child. The objective of the present study was to determine whether there is an excess of psychological and physical health problems among family caregivers (CGs) of elderly persons with dementia. Data were obtained by interview from close family members of dementia patients (CGs), and from a comparison group made up of close family members of patients undergoing cataract surgery (non-caregivers, NCGs). CGs had significantly higher levels of depression and physical symptoms than NCGs. The association between caregiving and the health variables was stronger among subjects who were the patient's spouse than among those who were the patient's child. Furthermore, greater behavioral disturbance in the demented patient was associated with higher levels of morbidity in the CG. The results suggest that CGs might benefit from careful monitoring of their health status, and from greater access to specialized support services. PMID- 1738014 TI - Evaluation of the properties and reliability of a clinical severity scale for acute asthma in children. AB - The inter-observer agreement (reliability) and validity of a clinical asthma severity scale (ASS) derived from separate scores of wheeze, heart rate and accessory muscle use (each on a 4-point scale) were studied in 60 children aged between 6 months and 17 years (mean 5.4 years). Independent assessments of these clinical parameters were made by two paediatricians, and they also rated patients as having a mild, moderate, severe or very severe acute episode (clinical judgement rating, CJR). Oxygen saturation (SaO2) was measured concurrently by a Biox 3700 pulse oximeter and readings were categorized as mild (SaO2 greater than or equal to 94%), moderate (91-93%) and severe (less than 91%). Agreement between clinicians was assessed by the weighted kappa statistic (kappa W). Agreement for the ASS score compared to the severity grade obtained from SaO2 was slight (kappa W = 0.34) and compared to CJR the kappa W was 0.55. An ASS score of moderate or worse (greater than 3) had sensitivity of 97% and specificity of 50% for prediction of admission. The maximum frequency and duration of nebulizer therapy following admission were significantly greater for severe patients than for moderate patients. Length of hospital stay did not reflect the ASS score in the emergency department but total duration of functional disability increased with ASS score. The substitution of an adjusted heart rate score for the raw heart rate score used in ASS detracted from scale performance. The ASS is an imprecise but reasonable quantitative measure of the severity of an acute episode of asthma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738015 TI - Gender differences in platelet count and its association with cigarette smoking in a large cohort in Israel. AB - Cigarette smoking has an effect on platelet function and aggregation although the sensitivity of platelet count in reflecting this phenomenon is not known. The association of platelet count with smoking habits was examined in a cohort of 5017 Israeli industrial workers aged 20-64 years. Males had a significantly lower age-adjusted mean platelet count than females (225,600 vs 247,800/microliters; p less than 0.001). Female smokers had lower platelet counts than non-smokers (231,000 for heavy vs 252,000 for never smokers) with a strong dose-response relationship (p less than 0.0001), whereas among males platelet count was slightly higher in smokers (224,000 for non-smokers vs 227,000 for heavy smokers; p = 0.243). The difference in platelet count between the sexes remained almost identical after controlling for smoking status and hematocrit. In multiple regression analysis, the negative association between smoking and platelet count in women remained highly significant (p less than 0.001) after controlling for ethnic origin, alcohol consumption, body mass, hematocrit, cholesterol and HDL cholesterol, whereas for males the slight positive association was not significant. The reduced platelet count observed in males compared with females and in female smokers, suggests that platelet count may reflect sex differences in hemostasis and the effects of smoking on the hemostatic system. This may have implications for the mechanisms underlying the pathogenesis of ischemic heart disease and should be explored further. PMID- 1738016 TI - What price perfection? Calibration and discrimination of clinical prediction models. PMID- 1738017 TI - Clinical epistemology of sensitivity and specificity. PMID- 1738018 TI - Long-term results after lateral canthal advancement for unilateral coronal synostosis. AB - The procedure of lateral canthal advancement was carried out to correct unilateral coronal synostosis in 39 consecutive patients at The Hospital for Sick Children during a 20-year period. Thirty-seven children were available for follow up study, and results were considered to be good or excellent in 81% of them. Liberation of the supraorbital margin and release of stenotic skull base sutures are crucial for a successful result. The severity of the process and the age of the patient were not restrictive factors in regard to indication for this procedure. Some patients showed a continuous improvement with time. Morbidity was minimal. It is suggested that lateral canthal advancement is the procedure of choice for unilateral coronal synostosis. PMID- 1738019 TI - Three-dimensional computerized tomography angiography in the diagnosis of cerebrovascular disease. AB - Computer-generated three-dimensional reconstruction of the intracranial vascular system obtained by contrast-enhanced computerized tomography (CT) has been used in the diagnosis of 20 patients with known or suspected intracranial cerebrovascular disease. This technique allows visualization of the intracranial vasculature without exposing patients to the risks associated with intra-arterial angiography. The color prints and videotape images generated have been used to diagnose the presence of intracranial aneurysms, arteriovenous malformations, and venous angiomas. They have also been used to rule out structural abnormalities in patients with suspected intracranial vascular pathology and to screen patients with a strong family history of intracranial aneurysm. In 11 patients who underwent both three-dimensional CT angiography and intra-arterial angiography, the diagnostic correlation was 100%. No complications from the procedures or from incorrect diagnosis have been encountered. Although this technique requires further development and clinical evaluation, the authors' early experience with three-dimensional CT angiography suggests that this may become a valuable tool in the diagnosis of patients with cerebrovascular disease. PMID- 1738020 TI - The relationship of blood flow velocity fluctuations to intracranial pressure B waves. AB - Intracranial pressure (ICP) and continuous transcranial Doppler ultrasound signals were monitored in 20 head-injured patients and simultaneous synchronous fluctuations of middle cerebral artery (MCA) velocity and B waves of the ICP were observed. Continuous simultaneous monitoring of MCA velocity, ICP, arterial blood pressure, and expired CO2 revealed that both velocity waves and B waves occurred despite a constant CO2 concentration in ventilated patients and were usually not accompanied by fluctuations in the arterial blood pressure. Additional recordings from the extracranial carotid artery during the ICP B waves revealed similar synchronous fluctuations in the velocity of this artery, strongly supporting the hypothesis that blood flow fluctuations produce the velocity waves. The ratio between ICP wave amplitude and velocity wave amplitude was highly correlated to the ICP (r = 0.81, p less than 0.001). Velocity waves of similar characteristics and frequency, but usually of shorter duration, were observed in seven of 10 normal subjects in whom MCA velocity was recorded for 1 hour. The findings in this report strongly suggest that B waves in the ICP are a secondary effect of vasomotor waves, producing cerebral blood flow fluctuations that become amplified in the ICP tracing, in states of reduced intracranial compliance. PMID- 1738021 TI - The relationship of ventricular drainage to aneurysmal rebleeding. AB - Given the widespread use of continuous external ventricular drainage in patients with aneurysmal subarachnoid hemorrhage (SAH), this investigation was undertaken to define the relationship of ventricular drainage to aneurysmal rebleeding. A historical cohort study of 128 patients with confirmed aneurysmal SAH was performed using a multivariate stepwise logistic regression analysis to examine the relationship between aneurysmal rerupture and ventricular drainage, while controlling for important clinical and radiological independent variables. The variables for ventricular drainage selected in the regression analysis were clinical grade, aneurysm size, and presence of hydrocephalus. The rate of rerupture was significantly higher in cases with ventricular drainage (odds ratio 5.31:1, p less than 0.05), poor clinical grade (odds ratio 4.90:1, p less than 0.02), and large aneurysm size (odds ratio 11.25:1, p less than 0.01). The significant effect of ventricular drainage was limited to patients with hydrocephalus. The increased risk of aneurysmal rebleeding in patients undergoing ventricular drainage may result from both: 1) a rise in aneurysmal transmural pressure, since intracranial pressure is lowered by ventricular drainage; and 2) an association between ventricular drainage and a more severely disrupted aneurysm which is more prone to rebleed as part of its natural history. This study found an increased risk of aneurysmal rebleeding among patients undergoing ventricular drainage, particularly in the presence of hydrocephalus. PMID- 1738022 TI - Oligodendrogliomas: the Mayo Clinic experience. AB - Eighty-one patients with pure supratentorial oligodendrogliomas underwent surgery alone (19 patients) or surgery plus postoperative radiation therapy (63 patients) between the years 1960 and 1982. The median survival time and the 5-, 10-, and 15 year survival rates for these 82 patients were 7.1 years, 54%, 34%, and 24%, respectively; these values were significantly different from those for an age- and sex-matched normal reference population. Univariate and multivariate survival analyses were performed on 13 possible prognostic factors including: patient age and sex; presence of seizures; site, size, side, computerized tomography (CT) enhancement, grade, and calcification of the tumor; and treatment (extent of surgical resection, lobectomy, radiation dose, and radiation field). Of these factors, tumor grade as classified by the Kernohan and St. Anne-Mayo methods was most strongly associated with survival. Patients with Grade 1 or 2 tumors by either grading method had a median survival time and 5- and 10-year survival rates of approximately 9.8 years. 75%, and 46%, respectively, compared to 3.9 years, 41%, and 20% for those with Grade 3 or 4 tumors. The extent of surgical resection was also associated with survival. The 19 patients who underwent gross total resection of their tumor had a median survival time and 5- and 10-year survival rates of 12.6 years, 74%, and 59%, compared to 4.9 years, 46%, and 23%, respectively, for the 63 who had subtotal resection. When comparing the 19 patients who underwent surgery alone with the 63 who had surgery plus postoperative radiation therapy, there did not appear to be a survival benefit to be gained from the addition of postoperative radiation therapy. However, the patients who had surgery alone tended to have gross total resections and lower tumor grades. Analysis of the subset of 63 patients who underwent subtotal resection alone or with radiation therapy showed that the median survival time and 5- and 10-year survival rates were: 2 years, 25%, and 25% for the eight patients with subtotal resection alone; 4.5 years, 39%, and 20% for the 26 patients with surgery and low-dose (less than 5000 cGy) radiation therapy; and 7.9 years, 62%, and 31% for the 29 patients receiving surgery and high-dose radiation therapy (greater than or equal to 5000 cGy), respectively. PMID- 1738023 TI - Early seizures after mild closed head injury. AB - The authors review the seizure incidence in 4232 adult patients with mild closed head injury who did not receive prophylactic anticonvulsant agents. One hundred patients (2.36%) experienced seizures within 1 week after head injury; 43 of these (1.02% of the series) had seizures within 24 hours after trauma. Most of the seizures (84%) that developed during the 1st week after injury were of the generalized tonic-clonic type. The incidence of generalized tonic-clonic seizures was higher than that of partial seizures with motor symptoms both within 24 hours (91% vs. 9%) and during the Day 2 to 7 period (79% vs. 21%). No definite intracranial pathological findings were detected by computerized tomography (CT) in 53% of patients with early posttraumatic seizures; six patients had intracranial hemorrhage without intracranial parenchymal damage (three with epidural hematoma and three with subarachnoid hemorrhage). The most common positive CT findings in the early posttraumatic-seizure group were intracerebral hemorrhage (24%), followed by acute subdural hematoma with intracerebral hemorrhage (17%). Intracerebral parenchymal damage could be identified on CT scans in 41 (48.8%) of 84 patients with generalized tonic-clonic seizures and five (31%) of 16 patients with partial seizures with motor symptoms. The intracerebral parenchymal damage was most commonly detected in the frontal lobe (21%) and the temporal lobe (19%). Seven patients with early posttraumatic seizures received emergency craniotomy to remove an intracranial hematoma (epidural in three, subdural and intracerebral in four) because the mass effect resulted in significant midline shift as seen on CT scans. This review suggests that early posttraumatic seizures after mild closed head injury have a high incidence (53%) in patients with normal CT scan findings. Although the possibility of surgically correctable intracranial hemorrhage is low (7%), the condition may be devastating if not treated properly. PMID- 1738024 TI - Surgical stabilization of cervical spinal fractures using methyl methacrylate. Technical considerations and long-term results in 52 patients. AB - This study analyzes the long-term outcome of 52 consecutively treated patients with acute cervical spinal fracture/dislocation who underwent posterior surgical stabilization using methyl methacrylate in the absence of bone grafting. The patients ranged in age from 15 to 93 years. In 40 patients the injury was located in the lower cervical spine; for these a previously described surgical format was employed. In 12 patients the fracture involved C-1 or C-2, and the modification used for these injuries is presented. The postoperative period of evaluation ranged from 6 months to 12 years. There was one case of infection, which eventually required removal of the acrylic, but there were no instances of new neurological injury or of operative mortality. Failure of stabilization occurred in two previously reported patients treated early in the series. Comparison of the patient outcome in this study with that of certain other reports suggests that at least four technical factors are important for the success of methyl methacrylate stabilization: 1) the acrylic inlay must be provided with an anchor to bone; 2) the anchor must be of a type that does not easily erode through bone; 3) the inclusion of wire must be done in a manner that allows each strand to be completely encased in the acrylic; and 4) the cross-sectional area of the inlay is critical. PMID- 1738025 TI - Stereotactic radiosurgical treatment of brain metastases. AB - In a series of 33 patients with reasonably controlled primary cancers, stereotactic radiosurgery was used to treat 52 brain metastases. After a mean radiological follow-up time of 5.5 months, six lesions (12%) had stabilized in size, 26 (50%) were significantly reduced, and 15 (29%) had disappeared. One large melanoma metastasis progressed relentlessly despite treatment. Five lesions (9%) had decreased in size slightly before enlarging. In two of these lesions, biopsy revealed only necrosis. In almost all cases, treatment was associated with decreased peritumoral edema. However, a group of patients with large metastases and extensive prior brain irradiation has been identified in whom prolonged symptomatic cerebral edema poses a problem. It is concluded that radiosurgery is a viable alternative to surgical resection for some cases of brain metastasis. PMID- 1738026 TI - Diffuse brain swelling in severely head-injured children. A report from the NIH Traumatic Coma Data Bank. AB - In this study, data were prospectively collected from 753 patients (111 children and 642 adults) with severe head injury and examined for evidence of diffuse brain swelling and its association with outcome. Diffuse brain swelling occurred approximately twice as often in children (aged 16 years or younger) as in adults. A high mortality rate (53%) was found in these children, which was three times that of the children without diffuse brain swelling (16%). Adults with diffuse brain swelling had a mortality rate (46%) similar to that of children, but only slightly higher than that for adults without diffuse brain swelling (39%). When the diagnosis of diffuse brain swelling was expanded to include patients with diffuse brain swelling plus small parenchymal hemorrhages (less than 15 cu cm), these mortality rates were virtually unchanged. PMID- 1738027 TI - Aneurysms arising from the proximal (A1) segment of the anterior cerebral artery. A study of 38 cases. AB - This study reviews aneurysms of the proximal segment (A1) of the anterior cerebral artery in 38 patients (23 men and 15 women) and their surgical, angiographic, and clinical management. Thirty-seven aneurysms were saccular and one was fusiform. The incidence of A1 aneurysms among a total of 4295 aneurysm cases treated was 0.88%. Multiple aneurysms occurred in 17 patients (44.7%) of the 38 cases; in 10 (58.8%), there was bleeding from the A1 aneurysm. The aneurysms were classified into five categories according to the mode of origin of the aneurysm in relation to the A1 segment: in 21 cases, aneurysms originated from the junction of the A1 segment and a perforating artery; in eight, from the A1 segment directly; in six, from the proximal end of the A1 fenestration; and in two, from the junction of the A1 segment and the cortical branch. One patient had a fusiform aneurysm. Computerized tomography (CT) of these aneurysms revealed bleeding extending to the septum pellucidum similar to that of anterior communicating artery aneurysms. When performing radical surgery it is very important to recognize the characteristics of A1 aneurysms, including multiplicity, a high incidence of vascular anomalies (especially A1 fenestration), and their similarity to anterior communicating artery aneurysms on CT. PMID- 1738028 TI - Intraforaminal repair of plexus spinal nerves by a posterior approach: an experimental study. AB - Many spinal nerve roots injured due to stretch or other types of lesions are not reparable. Some spinal nerves might be repaired if they could be exposed in their intraforaminal course. A posterior subscapular approach for a more lateral exposure of the brachial plexus was combined with a facetectomy to expose intraforaminal nerves in a series of Macaca rhesus monkeys. This approach exposed a 6- to 10-mm segment of spinal nerve not approachable by a more classic anterior operation. Sural grafts were placed from the dural exit of the spinal nerves to the cord level of the plexus. Nine surviving animals were followed for 36 to 54 months and observed for clinical evidence of return of function. In each animal at least one electromyogram (EMG) was performed. The plexus was then re-exposed and intraoperative nerve action potentials were recorded across graft sites. Evoked muscle action potential and cortical potentials were recorded in six animals. Despite the proximal level of repair, adequate regeneration was shown by clinical, electrical, and histological studies. Functional return was best to the supraspinatus and biceps muscles and to wrist and finger flexors. Clinical recovery was present, but less effective, for deltoid, wrist, and finger extensors and intrinsic muscles of the hand, despite evidence on EMG of reinnervation. Recovery of the infraspinatus muscle was poor. Nerve action potentials could be recorded across each graft site. Reinnervational activity was recorded by EMG and evoked muscle action potential studies in most of the muscles studied, despite the persistence of some denervational changes 3 years or more after injury and repair. Histological studies confirmed the presence of a large number of axons of moderate size and myelination even at the forearm level. PMID- 1738029 TI - Transient glucose hypermetabolism after acute subdural hematoma in the rat. AB - Ischemic brain damage occurs in most patients with acute subdural hematoma, yet many aspects of the distribution and extent of this damage remain unexplained. Previous studies in rat model, which produces a region of infarction under the hematoma, have implicated an "excitotoxic" mechanism, suggesting that high concentrations of excitatory amino acids may exacerbate ischemic damage. A study is described in which local glucose utilization is measured 2 or 4 hours after induction of acute subdural hematoma in the rat. These changes are compared to those produced by introducing the same volume of inert silicone gel into the subdural space. Massive increases (up to 142%) in glucose utilization occurred throughout both hippocampi and in a variable zone around the ischemic core, but these had normalized by 4 hours after blood injection. Hippocampal hypermetabolism was not seen after introduction of the silicone mass, suggesting that diffusible substances from the clotted blood may be responsible for these changes. This transient hypermetabolism accords with an excitotoxic process, which may amplify brain damage after acute subdural hematoma. PMID- 1738030 TI - Perfusion pressure breakthrough threshold of cerebral autoregulation in the chronically ischemic brain: an experimental study in cats. AB - A study was designed to investigate hyperperfusion syndrome after the restoration of normal cerebral blood flow in a chronically cerebral ischemic state resulting from high-flow arteriovenous malformations or severe carotid stenosis. A fistula between the left distal common carotid artery and the jugular vein was created and the left vertebral artery was simultaneously occluded in 44 cats to produce a chronic cerebral ischemic state. For control experiments, 10 cats underwent occlusion of the left common carotid and vertebral arteries. Six weeks later, pial arterial behavior, disruption of the blood-brain barrier (BBB), and cerebral histological changes were investigated using three experimental methods. In the first, in which a fistula was occluded under normal conditions, pial arteries contracted to some 80% of the resting state; however, no BBB disruption or histological changes were observed. In the second experiment, in which a 20 minute occlusion of the left middle cerebral artery was performed in the cats with a patent fistula, a 30% to 40% dilated state of the pial arteries continued after recirculation, and BBB disruption-induced cerebral edema and infarction were observed. These findings were more prominent in the cats that underwent occlusion of the fistula. On the other hand, in the control group, the pial arteries returned to resting size within 40 minutes, and no BBB disruption or histological changes were observed. In the third experiment, in which moderate hypertension was induced for 1 hour, the pial arteries dilated much more remarkably; BBB disruption and cerebral edema were revealed to be more extensive in the cases of fistula occlusion than within those with a patent fistula. In the control group, however, the pial arteries contracted 10% during hypertension, while BBB disruption and histological changes were not evident. The results indicate that the perfusion pressure breakthrough threshold in the chronically ischemic brain may not be reduced by the restoration of normal blood flow, but may be decreased by the addition of new ischemic insults or hypertension. PMID- 1738031 TI - Effect of mannitol on local cerebral blood flow after temporary complete cerebral ischemia in rats. AB - The effects of pretreatment with mannitol on local cerebral blood flow (CBF) after permanent or temporary global cerebral ischemia were evaluated with 14C iodoantipyrine autoradiography in rats under halothane-N2O endotracheal anesthesia. Blood pressure, pulse rate, arterial blood gas levels, and electroencephalographic (EEG) tracings were monitored throughout the experiments. After permanent occlusion of the basilar artery and both external carotid and pterygopalatine arteries, severe global ischemia was induced by permanent occlusion of the common carotid arteries (CCA's) or by a 30-minute temporary CCA occlusion followed by 5 minutes of reperfusion. Intravenous mannitol (25%, 1 gm/kg) or saline solution was administered 5 minutes before occlusion of the CCA's. Cerebral blood flow was measured in 24 anatomical regions. The EEG tracings flattened within 2 to 3 minutes after the onset of ischemia, and no recovery was observed during reperfusion. In the mannitol-treated rats and the saline-treated controls, autoradiographic studies after permanent occlusion showed no CBF in the forebrain or cerebellum, although brain-stem and spinal cord CBF values were normal. After 5 minutes of reperfusion, CBF in the cortex, basal ganglia, and white matter was 100% to 200% higher in mannitol-treated rats and 50% to 100% higher in saline-injected rats than in the nonischemic anesthetized control group. Heterogeneously distributed areas of no-reflow were seen in all saline-injected rats but were observed in none of the mannitol-treated rats. Pretreatment with mannitol prevented postischemic obstruction of the microcirculation during 5 minutes of recirculation after 30 minutes of severe temporary ischemia, but the EEG signals did not recover. Further studies of the functional and morphological responses to longer periods of postischemic recirculation are needed to verify the extent to which these mannitol-induced effects are protective. PMID- 1738032 TI - Time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage in primates. AB - The time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 18 monkeys. Changes in cerebral blood flow (CBF) at the regional level and central conduction times during either graded hypo- or hypertension were evaluated in these animals at three stages (3, 7, and 14 days) following the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber (compared to the baseline level in the involved MCA) of 30% at 3 days, 50% at 7 days, and 10% at 14 days. At all stages, CBF remained constant at mean arterial blood pressures (MABP) of 60 to 160 mm Hg in the noninvolved hemisphere. In contrast, at the 3- and 7-day stages, there was an impairment of autoregulation in the involved hemisphere at MABP of 40 to 180 mm Hg. The right hemispheric CBF was significantly (p less than 0.05) lower than that in the left throughout the period of investigation at MABP below 120 mm Hg, but rose to exceed the left CBF at MABP above 180 mm Hg at the 7-day stage and 160 mm Hg at the 14-day stage. The right-sided central conduction time showed significant (p less than 0.05) prolongation at MABP below 60 mm Hg at the 3-day stage and 40 mm Hg at the 7-day stage. It is suggested that these results may help to develop guidelines for hemodynamic therapy for vasospasm in its various stages. PMID- 1738033 TI - Treatment of murine primary brain tumors with systemic interleukin-2 and tumor infiltrating lymphocytes. AB - Methods have recently been described for the isolation and expansion of lymphocytes that have trafficked into animal and human tumors. These CD8-positive tumor-infiltrating lymphocytes (TIL's) have exceptional trafficking ability to, and efficacy against, tumor targets in extracranial sites. Prior to Phase I clinical trials for patients with gliomas, adoptive immunotherapy with TIL's was studied in a mouse model of primary brain tumors to determine if intracerebral tumors have a similar response. Glioma 261 (GL261) tumors were grown in the subcutaneous space of C57BL/6 mice. After enzymatic digestion, the cells were incubated in vitro with interleukin-2 (IL-2) until a confluent population of T lymphocytes was present. The in vitro efficacy of these TIL's was tested against fresh GL261 targets with a chromium release assay; the in vivo efficacy was tested against GL261 tumors in the liver and against irradiated and nonirradiated GL261 tumors in the brain. Mice received one of the following: intraperitoneal saline; intraperitoneal IL-2 (7500 to 50,000 U three times daily for 5 days); IL 2 plus intravenous TIL's (1 to 3 x 10(7) cells); 10 Gy cranial irradiation; irradiation plus IL-2; or irradiation plus IL-2 plus TIL's. The TIL preparation killed 77% of tumor targets in 4 hours at an effector:target ratio of 100:1. In animals with GL261 tumors in the liver, at 2 weeks there were 93 +/- 37, 128 +/- 45, and 21 +/- 14 liver metastases in the control, IL-2, and IL-2 plus TIL groups, respectively. However, in animals with GL261 tumors in the brain, no treatment group had an increased survival rate compared to the control group. It is concluded that, although TIL and IL-2 immunotherapy can be used effectively to treat brain tumors in vitro and at sites outside the central nervous system, it is ineffective against the same type of tumor in the brain. Different methods of delivery or different combinations of these immunomodulators may be more effective; however, based on these findings, treatment of patients with IL-2 and TIL cannot be recommended until efficacy has been demonstrated in an animal model. PMID- 1738034 TI - Direct approach to a traumatic giant internal carotid artery aneurysm associated with a carotid-cavernous fistula. Case report. AB - The case is reported of a giant intracranial internal carotid artery aneurysm associated with a carotid-cavernous fistula following a closed head injury. The aneurysm and the fistula disappeared after only the neck of the aneurysm was clipped. This is the first case in which a direct surgical approach was successful in sparing the internal carotid flow. Reports of similar cases are reviewed. PMID- 1738035 TI - Intramedullary epidermoid cysts of the spinal cord. Case report. AB - Epidermoid cysts are tumors familiar to neurosurgeons, but intramedullary epidermoid cysts are rare. The authors report the case of a 6-year-old girl presenting with progressive paraparesis. A midthoracic intramedullary mass was revealed on myelography and magnetic resonance (MR) imaging and confirmed as an intramedullary epidermoid cyst at surgery, at which time the cyst was removed. This is the fourth report documenting a purely intramedullary epidermoid cyst occurring in a child. The pathology and etiology, epidemiology, clinical features, radiology (including MR image characteristics), and surgical treatment of such rare intramedullary benign tumors are discussed. Magnetic resonance imaging reduces the delay in diagnosis of spinal cord tumors but should be guided by clinical judgment. PMID- 1738036 TI - Ligamentum flavum hematoma. Report of two cases. AB - Two patients presenting with signs and symptoms suggestive of nerve root compression secondary to extradural masses were found to have ligamentum flavum hematomas. Both patients had neurological deficits preoperatively and regained normal function postoperatively. There was no significant antecedent injury in either case. The symptom course was longer than that for spontaneous epidural hematoma. In one case, there was remodeling of bone, initially suggesting either infection or tumor. PMID- 1738037 TI - Cerebral protection during aneurysm surgery with isoflurane anesthesia. Technical note. AB - A strategy for intraoperative cerebral protection is described in which intraoperative electroencephalography is used to titrate the level of inspired isoflurane given for anesthesia to obtain isoelectricity prior to temporary vessel occlusion during repair of difficult aneurysms. During temporary vessel occlusion, arterial blood pressure is maintained or increased with an inotropic or vasopressor agent. After clipping of the aneurysm, the concentration of isoflurane is reduced to allow the patient to awaken in the operating room for early postoperative neurological examination. The combination of a high concentration of isoflurane, temporary vessel occlusion, and maintenance of arterial blood pressure may be a useful protective regimen during neurovascular procedures. PMID- 1738038 TI - A portable traction device for cervical fractures. Technical note. AB - A lightweight and completely self-contained traction device is described. It has been used to immobilize the cervical spine during radiographic evaluation and treatment of patients with cervical fracture, and for therapeutic traction in patients with a ruptured disc. Other applications are possible, but have not yet been investigated. PMID- 1738039 TI - End-to-side anastomosis of small vessels using an Nd:YAG laser with a hemispherical contact probe. Technical note. AB - A new technique is described which enables the surgeon to perform an end-to-side anastomosis between arteries with little (less than 2 minutes) or no occlusion of the recipient artery. The technique was developed in rabbits, but has recently been successfully used in a patient in whom an anastomosis between the superficial temporal artery and a proximal branch of the middle cerebral artery was created. PMID- 1738040 TI - Two examples of ancient skull surgery. AB - The author, while a research illustrator at the Smithsonian Institution National Museum of Natural History, studied two ancient skulls from the Incan period in Peru, both with trephination. Her conclusions and illustrations of the skulls are included in this paper. PMID- 1738041 TI - Brain tolerance to radiosurgery. PMID- 1738042 TI - Complications of radiosurgery for brain AVM's. PMID- 1738043 TI - Instrumentation for spinal trauma. PMID- 1738044 TI - Myelotomy in spinal spasticity. PMID- 1738045 TI - Prediction tree for severely head-injured patients. PMID- 1738046 TI - Efficiency of stereopsis in random-dot stereograms. AB - The statistical efficiency of stereopsis was investigated by measurement of the discriminability d' of a step edge in depth in a random-dot stereogram and its comparison with d' calculated for an ideal observer model. Efficiencies of approximately 20% were found for stimuli with very few (less than 30) dots. As the number of dots was increased, efficiency fell markedly to 2% and below. Over the ranges explored in this study, there was little variation in efficiency with changes in dot density (with dot number constant) or stimulus size. Efficiency loss was also found to be almost entirely due to incomplete use of the available information rather than to intrinsic observer variance. Results were compared with two simple models that implemented possible detection strategies. PMID- 1738047 TI - Experimental test of an analytical model of aberration in an oil-immersion objective lens used in three-dimensional light microscopy. AB - Oil-immersion microscope objective lenses have been designed and optimized for the study of thin, two-dimensional object sections that are mounted immediately below the coverslip in a medium that is index matched to the immersion oil. It has been demonstrated both experimentally and through geometrical- and physical optics theory that, when the microscope is not used with the correct coverslip or immersion oil, when the detector is not located at the optimal plane in image space, or when the object does not satisfy specific conditions, aberration will degrade both the contrast and the resolution of the image. In biology the most severe aberration is introduced when an oil-immersion objective lens is used to study thick specimens, such as living cells and tissues, whose refractive indices are significantly different from that of the immersion oil. We present a model of the three-dimensional imaging properties of a fluorescence light microscope subject to such aberration and compare the imaging properties predicted by the model with those measured experimentally. The model can be used to understand and compensate for aberration introduced to a microscope system under nondesign optical conditions so that both confocal laser scanning microscopy and optical serial sectioning microscopy can be optimized. PMID- 1738048 TI - Color changes in red and white projections at low luminance. AB - In previous studies photographic projections containing only mixtures of red and white light produced a wide variety of hues. In the present experiment similar patterns were produced on a color monitor. Squares with four combinations of red and white light were studied at two mean luminances. Subjects reported that a chromaticity that appeared pink at our higher luminance appeared yellow at low luminance. PMID- 1738049 TI - Visual instrument image quality metrics and the effects of coma and astigmatism. AB - We examine subjective contrast and edge sharpness discrimination in the presence of different amounts of coma, astigmatism, and combinations of these two aberrations. We also examine the correlation between subjective results and objective image quality measures. These include the integral of the modulation transfer function (MTF) across the frequency range of interest (MTFa), the Strehl ratio, the variance of the wave-front aberration, and the radius of 84% encircled energy of the point-spread function (R84). For the target orientation that is most affected by the aberrations, we find that the MTFa and R84 give good correlation, while the Strehl ratio and the variance do not. In addition, we find that the MTFa correlates with subjective results for all target orientations. We discuss the implications of the results on the automated assessment of the image quality of visual instruments. PMID- 1738050 TI - Size of saccade and fixation duration of eye movements during reading: psychophysics of Japanese text processing. AB - The size of saccadic eye movements and eye fixations during Japanese text reading (written in both hirakana phonograms and kanji ideograms) were analyzed. Hirakana is sound based, i.e., it consists of symbols for syllables, but such text was processed differently from English text in terms of saccadic eye movements and fixations. In experiment 1 the reader was asked to read three types of text (hirakana only, kanji-hirakana mixed, and English) in a natural reading manner. The results show that kanji-hirakana-mixed text, which has picturelike symbols, requires shorter eye fixations and longer saccades than those required by hirakana text. The findings show that kanji and hirakana are processed differently. Logographlike kanji text greatly facilitated text processing and understanding during reading. In experiment 2 we found that kanji-based text had a wider perceptual span of reading than did hirakana text. The wider span is consistent with the longer saccade length for kanji-based text found in experiment 1. In experiment 3 we studied the convenient viewing position, i.e., the position within a word where the eye should fixate first for the isolated word to be recognized most quickly. A convenient viewing position was confirmed to exist both for hirakana- and kanji-based words, but for hirakana words the position changed as word length changed, as was expected from the results of experiment 2. In experiment 4 we measured lexical access time for hirakana- and kanji-based words and found that the reaction time to kanji-based words was faster than the reaction time to words written with hirakana.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738051 TI - Molecular and biochemical aspects of nematode collagens. AB - Collagens are major structural proteins of nematode cuticles and basement membranes (basal laminae). The collagen proteins that form these structures differ in their biochemical and physical properties and are encoded by distinct gene families. Nematode basement membrane collagens are large proteins that show strong homology to basement membrane collagens of vertebrates. There appear to be 2 nonidentical basement membrane collagen genes in nematodes. Cuticle collagens are about one-sixth the size of basement membrane collagens and are encoded by a large family of 20-150 nonidentical genes. Cuticle collagens can be subdivided into 4 families based upon certain structural features in the proteins. The mature, extracellular forms of both types of collagen proteins are extensively cross-linked by disulfide bonds and are largely insoluble in the absence of a thiol-reducing agent. Cuticle collagens also are cross-linked by nonreducible covalent bonds that involve tyrosine residues. The experimental studies that have led to our current understanding of the structures of basement membrane and cuticle collagens are reviewed. Some previous questions about the physical properties of these proteins are reexamined in light of the primary sequence information now available for the proteins. PMID- 1738052 TI - Excretory-secretory products of Echinostoma paraensei sporocysts mediate interference with Biomphalaria glabrata hemocyte functions. AB - Miracidia of Echinostoma paraensei were cultured in medium containing 14C-labeled amino acids, allowed to transform into sporocysts, and their excretory/secretory products (E-S) were collected and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Effects of E-S on hemocytes of Biomphalaria glabrata were also assessed. E-S collected during day 1 of culture (E-S1) contained several polypeptides, none of which were labeled, suggesting that E-S1 are largely preformed. E-S1 significantly depressed the ability of hemocytes to phagocytose sheep red blood cells (SRBC), but otherwise had little effect on hemocyte structure or behavior. E-S released by sporocysts in day-2 cultures (E-S2) and in older cultures generally were similar and also contained several polypeptides, many of which were labeled, indicating active synthesis of E-S in vitro. E-S2 strongly inhibited hemocyte uptake of SRBC. Also, hemocytes pretreated with E-S2 assumed a spherical shape and failed to spread normally. E-S obtained through 10 days of culture mediated this effect. Active components of E-S2 were greater than 100 kDa in their native configuration, were heat- and trypsin-labile, and were bound by anti-E-S antibodies. Both greater than 200- and 80-kDa bands were prominent in anti-E-S immunoprecipitates. Hemocytes derived from snails of the 13-16-R1 strain of B. glabrata (a strain resistant to infection with Schistosoma mansoni), when pretreated with E-S2, bound to sporocysts of S. mansoni but lost their ability to damage such sporocysts. E-S2 interfered with hemocyte functions in ways inferred from earlier classic in vivo studies of trematode-snail interactions. PMID- 1738053 TI - Sarcocystis falcatula of opossums: transmission by cockroaches with fatal pulmonary disease in psittacine birds. AB - Old World psittacines experienced an acute fatal illness in outdoor breeding collections in South Florida. Toxoplasma-like organisms were found histologically in pulmonary capillaries and elsewhere. Because the organisms underwent schizogony and could not be transmitted to mice, we looked for a cause other than Toxoplasma gondii. An opossum was trapped on the premises of 1 facility and was found to be shedding sporocysts similar to Sarcocystis falcatula in its feces. Cockroaches were prevalent and suspected as transport hosts. Cockroaches that had ingested opossum feces and subsequently were fed to cockatoos induced an identical fatal illness. Obstruction of pulmonary capillaries by developing schizonts and pulmonary edema were the most important pathologic findings. The epidemic was stopped by biological insect control employing flightless chickens to reduce cockroach populations and by an electric fence restricting access of opossums to these outdoor psittacine breeding facilities. PMID- 1738054 TI - Effects of albendazole on Gnathostoma spinigerum in mice. AB - Mice were infected with 5 advanced third-stage larvae of Gnathostoma spinigerum and, beginning on the 28th day postinfection, were treated orally with albendazole. In the first experiment, infected mice each received albendazole once a day (30, 60, or 90 mg/kg/day) for 21 consecutive days. In the second experiment, they received albendazole twice a day (30 and 30, 60 and 60, or 90 and 90 mg/kg/day) for the same length of time. All mice were killed 28 days after cessation of treatment and the carcasses were examined for parasites. With both regimens, the administration of albendazole significantly reduced the number of larvae. However, a complete larvicidal effect was obtained only with albendazole at the dosage of 90 mg/kg twice daily. PMID- 1738055 TI - Formation of the capsule around Filicollis anatis (Acanthocephala) in its intermediate host. AB - Morphogenesis of the capsule around larvae of Filicollis anatis was studied by electron microscopy. The capsule is formed at early, middle, and late acanthella development. The inner layer is formed at the late acanthella stage apparently from material secreted via a system of hypodermal canals. The central layer of the capsule is formed mainly of detached microvilli of the acanthella. The source and mechanism of formation of the outer layer, which appears during the early acanthella stage, are unclear. PMID- 1738056 TI - Cold-hardiness in Pelecitus fulicaeatrae (Nematoda: Filarioidea), a parasite of the ankles of Fulica americana (Aves). AB - The filarioid nematode Pelecitus fulicaeatrae (Diesing, 1861) is considered cold hardy. Adults and microfilariae became motile when placed in saline at 22 C after having been removed from thawed carcasses of their host, the American coot (Fulica americana Gmelin) (Aves: Gruiformes). Adult nematodes from 5 of 12 carcasses became active as did microfilariae from 4 of 5 carcasses. Carcasses had been frozen at an undetermined temperature below 0 C for an initial 14 days and then at -21 to -24 for 100-159 days. PMID- 1738057 TI - The use of the polymerase chain reaction to identify porcine isolates of Trichinella. AB - A method was developed to identify domestic isolates of Trichinella using the polymerase chain reaction. Oligonucleotide primers, based on the repetitive DNA sequence (pPRA) from the P1 isolate of Trichinella, were used to amplify genomic DNA from 13 domestic isolates and tested against sylvatic isolates of Trichinella. Pattern differences were observed among domestic isolates, indicating divergence of this repetitive sequence. The primers were specific for domestic Trichinella as no amplification was detected for sylvatic isolates or Trichinella pseudospiralis. It was possible to identify an isolate from a single larva following digestion or in situ in muscle tissue. PMID- 1738058 TI - Experimental Caryospora bigenetica (Apicomplexa: Eimeriidae) infections in swine (Sus scrofa). AB - Two Hampshire-Landrace crossbred pigs were found to contain developmental stages of Caryospora bigenetica following oral inoculation with 1 x 10(8) oocysts. One pig was given intramuscular injections of methylprednisolone acetate. Both pigs displayed clinical signs of dermal coccidiosis from 3 to 10 days after inoculation, including swollen jowls and hocks, bilateral ocular discharges, generalized erythema, and lethargy. Meronts and gamonts were observed histologically in numerous tissues including jowl, ear, footpad, tongue, and lung at 10 days postinoculation. The present study is the first report of C. bigenetica infections in swine. PMID- 1738059 TI - Isolation of Toxoplasma gondii from a naturally infected beef cow. AB - Toxoplasma gondii was isolated from the intestinal wall of an adult shorthorn cow. The cow had an antibody titer of 1:1,600 in the T. gondii agglutination test using formalin-fixed whole tachyzoites. The strain of the parasite designated CT 1 was lethal to mice. This is the first report of the recovery of viable T. gondii from a naturally infected cow in the United States. PMID- 1738060 TI - Psoroptes sp. in two llamas (Lama glama) in Washington. AB - Psoroptes sp. mites were isolated from two llamas (Lama glama), a 4-mo-old male and its dam, in Washington. Mites were restricted to the ears and were responsible for head-shaking and incoordination. Infestations were treated successfully with a subcutaneous injection of ivermectin at 0.2 mg/kg of body weight and with 2 drops of ivermectin diluted in saline given topically in each ear. This is the first known report of Psoroptes sp. in llamas in the United States. PMID- 1738061 TI - How effective is the agar plate method for Strongyloides stercoralis? AB - The sensitivity of the agar plate method for the diagnosis of Strongyloides stercoralis was studied experimentally. Results demonstrated that this method was sensitive enough to detect S. stercoralis even when only a few worms were present. PMID- 1738062 TI - Survival of Onchocerca volvulus in nodules implanted in immunodeficient rodents. AB - Onchocerca volvulus is an obligate human parasite, and its study has been difficult due to an inability to maintain it outside the human host. We report the successful transplantation of onchocercomata containing living adult O. volvulus worms into immunodeficient C.B.-17.scid/scid (scid) mice or athymic rnu/rnu (nude) rats. Living, motile worms containing viable microfilariae were present in onchocercomata recovered from scid mice or nude rats for up to 20 wk, establishing a novel animal model for future investigation of O. volvulus. PMID- 1738063 TI - Helminth parasites of the raccoon (Procyon lotor) from north-central Arkansas. AB - Twenty-three species of helminths (4 trematodes, 2 cestodes, 14 nematodes, and 3 acanthocephalans) were found in the gastrointestinal tract, lungs, pancreas, tongue, urinary bladder, and subcutaneous tissues of 30 live-trapped or hunter shot raccoons from north-central Arkansas between November 1989 and April 1990. Helminths were not detected in the brain, diaphragm, gallbladder, heart, liver, reproductive system, or trachea. Each raccoon examined was infected with 3 or more of the following helminths: Brachylaima virginiana, Eurytrema procyonis, Fibricola cratera, Pharyngostomoides procyonis, Atriotaenia procyonis, Mesocestoides spp., Arthrocephalus lotoris, Capillaria aerophila, Capillaria plica, Capillaria procyonis, Capillaria putorii, Crenosoma goblei, Cruzia americana, Dirofilaria tenuis, Dracunculus insignis, Enterobius sp., Gnathostoma procyonis, Molineus barbatus, Physaloptera rara, Trichinella spiralis, Centrorhynchus wardae, Macracanthorhynchus ingens, and Oligacanthorhynchus tortuosa. All helminths collected with the exception of D. insignis constitute new geographic distribution records. Occurrences of C. aerophila, C. wardae, and O. tortuosa are new host records. One nymphal pentastome, Porocephalus crotali, was found in the liver of 1 raccoon, constituting a new host record. PMID- 1738064 TI - Identification of Dirofilaria immitis-infected dogs with a coagglutination assay. AB - The presence of Dirofilaria immitis excretory-secretory (ES) products was detected in the urine of infected dogs using a coagglutination assay. Urine samples from 30 naturally infected dogs were positive. Seventeen of them were microfilaremic, whereas 13 had become amicrofilaremic after receiving 2 courses of diethylcarbamazine. Urine samples from 20 dogs infected with other parasites, Dipetalonema reconditum (7), Toxocara canis (5), and Ancylostoma caninum (8), and urine samples from 20 healthy dogs were negative. The assay detected 200 ng/ml or more of ES products. This assay is simple, easy to perform with minimum training, and requires no equipment. Therefore it should be useful to detect canine filariasis under field conditions. PMID- 1738065 TI - Enzymes of the tricarboxylic acid cycle in Ancylostoma ceylanicum and Nippostrongylus brasiliensis. AB - Enzymes of the tricarboxylic acid (TCA) cycle and glyoxylate pathway were investigated in adults and infective larvae of Ancylostoma ceylanicum and Nippostrongylus brasiliensis, and their activities were compared with those obtained in rat liver. A complete sequence of enzymes of the TCA cycle, with most of them showing activities quite similar to those in the rat liver homogenate, was detected in adults of both species. All the enzymes except fumarase and malate dehydrogenase were located predominantly in mitochondria where they showed a variable distribution of activities between the soluble and the membranes fractions. Malate dehydrogenase and fumarase were found in both the mitochondria and the 9,000-g supernatant fraction. Succinyl CoA synthetase, which was present in minimum activity, appeared rate limiting. Enzymes of the glyoxylate pathway, particularly isocitrate lyase, seemed to aid the functioning of the Krebs cycle by allowing the formation of succinate from isocitrate. The infective larvae of both species also were found equipped with all the enzymes of the Krebs cycle. Nonetheless, only isocitrate lyase of the glyoxylate pathway could be detected in these parasites. PMID- 1738066 TI - Redescription of Hebesoma violentum Van Cleave, 1928 (Acanthocephala: Neoechinorhynchidae). AB - Hebesoma violentum Van Cleave, 1928, is redescribed from 155 paratypes from Van Cleave's original 1921 and 1923 collections in China. The present distribution of H. violentum in China and the Soviet Union is reported and the uncertain status of Hebesoma derosum Gupta and Jain, 1973, examined. PMID- 1738067 TI - Description and pathology of Neoechinorhynchus idahoensis n. sp. (Acanthocephala: Neoechinorhynchidae) in Catostomus columbianus from Idaho. AB - Neoechinorhynchus idahoensis is described from Catostomus columbianus caught in the Salmon River, Stanley Basin, Idaho. The new species is closest to Neoechinorhynchus venustus Lynch, 1936, but is distinguished from it by its smaller and variably structured eggs, anterio-dorsal trunk hump, bent and posteriorly notched proboscis receptacle, and larger proboscis, proboscis receptacle, and hooks. It is distinguished also from 2 other species of Neoechinorhynchus with proboscis hooks in middle and anterior circles about equally large and from 7 other species having lemnisci greatly unequal in length. Histopathology of host tissue showed limited host response exemplified by epithelial damage and hemorrhaging at point of proboscis attachment with subsequent macrophage and other phagocytic cell migration. The proboscis extended through the host epithelium into the submucosa with limited hemorrhaging at the point of attachment. Unorganized collagenous fibers were present. The lumen of the host intestine was obstructed, and compressed villi were present. The trunk of the worm damaged intestinal epithelium near the crypts, causing localized inflammation. The caryophyllaeid cestode Isoglaridacris calentinei Mackiewicz, 1974, was present in concurrent infections of C. columbianus. PMID- 1738068 TI - Biological tags for stock separation in Pacific herring Clupea harengus pallasi in California. AB - A survey of the parasites of Pacific herring (Clupea harengus pallasi) off northern California identified 1 species of Acanthocephala, 1 species of Cestoda, 2 species of Copepoda, 1 species and 1 family of Digenea, 3 species of Nematoda, and 3 species of Protozoa. From this survey, Lacistorhynchus dollfusi (Cestoda), Parahemiurus merus (Digenea), and Anisakis simplex, Contracaecum sp., Hysterothylacium sp. (Nematoda) were selected as potential tags. Herring were collected in Tomales, San Francisco, and Monterey bays for the following 9 yr and examined for these select parasites. The results suggest that these parasites can be used to distinguish the spawning stocks of San Francisco and Tomales bays. The distribution of the definitive hosts of the respective parasites suggests that the Tomales Bay fish are offshore during the nonbreeding season and the San Francisco Bay fish onshore. The similarity in parasitism between San Francisco Bay and the nonspawning population in Monterey Bay suggests that these 2 populations represent a single stock. PMID- 1738069 TI - Pattern of cercarial emergence of Schistosoma curassoni from Niger and comparison with three sympatric species of schistosomes. AB - The emergence pattern of Schistosoma curassoni cercariae from Bulinus umbilicatus, whose adult worms parasitize bovine, caprine, and ovine ungulates in Niger, is of a circadian type with a mean emission time at 0855 hr +/- 1 hr 6 min, characteristic of the schistosome species parasitizing domestic or wild cattle. The comparison of this cercarial emergence pattern with those of the other 3 sympatric species of schistosomes (Schistosoma haematobium, Schistosoma bovis, and Schistosoma mansoni) shows a significant difference between the chronobiology of the cercariae infective for human and those infective for bovine hosts. This difference may improve epidemiological surveys based on snail prevalences by allowing the distinction between bulinids infected with human and bovine parasites. PMID- 1738070 TI - Use of confidence ellipses to detect effects of parasites on the growth of yellow perch, Perca flavescens. AB - Determining the causes of mortality in populations of fish is inherently difficult. To simplify the determination of whether parasite-induced mortality occurs, parasitologists have relied on 3 types of subjective analyses of graphs. Peaked host age-parasite intensity curves concomitant with a decrease in the degree of dispersion (measured by variance-to-mean ratio) of parasites in older age-classes of fishes, a slope of less than 2.0 for a log-log graph of variance versus mean intensity of infection, and differences between truncated and nontruncated forms of a theoretical frequency distribution for the parasite are considered indicators of parasite-induced mortality in fishes. The nematode Raphidascaris acus causes significant parasite-induced mortality in natural populations of yellow perch (Perca flavescens) in Dauphin Lake, Manitoba, Canada. Using this fish-parasite system we present a comparison of some of the graphical techniques used by parasitologists to detect parasite-induced mortality and show how confidence ellipses based on the parameters beta 0 and beta 1 of a linear model for growth of yellow perch (weight = beta 0 + beta 1 x age) can be used to compare many growth curves simultaneously. When plotted in a bivariate fashion (beta 0 vs. beta 1), vertical displacement of confidence ellipses along the ordinate (beta 1) are due to sublethal effects on growth of fishes in response to parasites, whereas lateral shifts along the abscissa (beta 0) are suggestive of parasite-induced mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738071 TI - Factors affecting the survival of Neospora caninum bradyzoites in murine tissues. AB - Studies were conducted to determine factors that influence the survival of bradyzoites of Neospora caninum within tissue cysts in the brains of experimentally inoculated mice. Viable tissue cysts were detected in the brains of mice inoculated 13 mo previously with either of 2 isolates (NC-1 or NC-2) of N. caninum. Bradyzoites within tissue cysts of the NC-2 isolate survived for at least 14 days at 4 C in refrigerated brain homogenates. Bradyzoites within tissue cysts of the NC-2 isolate also survived in the intact brain of a mouse carcass refrigerated at 4 C for 7 days. Bradyzoites within tissue cysts of the NC-3 isolate were killed by freezing at -20 C for 1 day. PMID- 1738072 TI - Relative susceptibility of Giardia muris trophozoites to killing by mouse antibodies of different isotypes. AB - The aim of this work was to examine the ability of mouse IgA, IgG, and IgM anti Giardia antibodies to kill Giardia muris trophozoites in the presence and absence of complement. Using a 2-color flow cytometry assay, binding of antibody to trophozoites was assessed with fluorescein-conjugated anti-mouse immunoglobulin, and percentages of killed trophozoites were quantified by staining with propidium iodide. Trophozoites were killed in the presence of complement by IgG3 and IgM anti-trophozoite monoclonal antibodies. Anti-trophozoite IgA, obtained from the intestinal lumen of G. muris-infected BALB/c mice, became bound to trophozoites in vitro but did not kill these organisms in the presence or absence of complement. The results suggest that clearance of G. muris infection by intestinal IgA directed against G. muris trophozoites does not involve antibody dependent killing of trophozoites in the intestinal lumen. PMID- 1738073 TI - Effects of immunization of rabbits on establishment, survival, and reproductive biology of the tick Hyalomma anatolicum anatolicum. AB - Four antigenic preparations, viz. salivary gland antigen (SG Ag), whole tick extract antigen (WTE Ag) and 30,000-g supernatant fraction, and pellet of WTE Ag (TES Ag and TEP Ag, respectively), were made from partially fed adult female Hyalomma anatolicum anatolicum. Four groups of 5 rabbits each were immunized with the antigens, and a fifth group was kept as control. Following challenge with adult H. a. anatolicum, a significant decrease in engorgement weight and egg mass weight and an increase in engorgement period and preoviposition period were observed in WTE Ag-immunized rabbits. Similar results were observed with TES Ag and SG Ag, except that change in the engorgement period was insignificant. However, none of the tick parameter measurements showed significant changes with TEP Ag. None of the antigens produced significant changes in the percentage of engorgement or oviposition period of the challenged ticks. Thus, WTE Ag was the most effective in altering tick performances. PMID- 1738074 TI - Electrophoretic and immunologic characterization of proteins of merozoites of Eimeria acervulina, E. maxima, E. necatrix, and E. tenella. AB - Merozoites of Eimeria acervulina, Eimeria maxima, Eimeria necatrix, and Eimeria tenella were compared by gel electrophoresis, western-blotting with chicken antiserum, indirect fluorescent antibody reactions, and antiserum neutralization. Merozoites from the 4 species had dissimilar patterns of proteins and antigens in soluble and membrane fractions. Coomassie blue staining of SDS-PAGE gels revealed 16-22 protein bands depending on the species of merozoite but only 3 bands per species in the membrane fractions. Homologous and heterologous antisera recognized 5-12 soluble fraction bands and 3-7 membrane fraction bands on immunoperoxidase-stained western blots, depending on the species. When antisera from infected chickens were used in an indirect fluorescent antibody reaction, the merozoites of E. tenella and E. necatrix had a strong reaction with homologous and heterologous antisera. Merozoites of E. acervulina and E. maxima reacted with homologous antisera but had a weak or no reaction with heterologous antisera. Chicken antiserum against E. tenella had no effect on the viability of E. tenella merozoites when they were inoculated into chicken embryos. PMID- 1738075 TI - Vector specificity of Trypanosoma catostomi and its infectivity to freshwater fishes. AB - Trypanosoma catostomi was found in 36.2% of 558 white suckers (Catostomus commersoni) from Ontario, Canada. The abundance of Actinobdella inequiannulata was 35% (68 leeches/197 suckers examined for leeches). The susceptibility of 3 species of leeches (Hemiclepsis marginata, Desserobdella phalera, and A. inequiannulata) and 7 species of fishes (C. commersoni, Amia calva, Anguilla rostrata, Ictalurus nebulosus, Oncorhynchus mykiss, Perca flavescens, and Esox lucius) to infection with T. catostomi was examined. Metatrypanosomes were found in the crop and proboscis sheath of 13 of 21 A. inequiannulata and in the crop of 10 of 12 H. marginata and 1 of 21 D. phalera. Only flagellates from A. inequiannulata were infective to C. commersoni. Cultured T. catostomi infected C. commersoni and A. calva but not any other fish species. Laboratory-reared C. commersoni were more susceptible than wild-caught specimens. Cultured Trypanosoma phaleri did not infect its natural host, A. calva. Host specificity should be established experimentally before a specific diagnosis is made. Cultures may be useful in simulating factors that affect development in the vector. PMID- 1738076 TI - Role of synganglion in oogenesis of the tick Ornithodoros parkeri (Acari: Argasidae). AB - The role of the synganglion in oocyte development in Ornithodoros parkeri was investigated by ligation and transplantation experiments. Ligation between legs 2 and 3 to isolate the synganglion from the ovary and ligation between legs 1 and 2 to keep both the synganglion and the ovary in the posterior ends were performed on mated females on different days after feeding. Results show that vitellogenesis was inhibited significantly if the synganglion was separated from the ovary within the first few days after feeding. However, transplantation of synganglia from 3 kinds of donors (unfed virgin, fed virgin, and fed mated females) into the synganglionless posterior portions induced vitellogenesis and oocyte development to final maturation. The supra- and subesophageal parts of the synganglion showed a similar gonadotropic activity after each was transplanted separately into the ligated synganglionless posterior portions. These results indicate that the synganglion produces an egg development stimulation factor (EDSF) that possibly is present in a storage form in unfed and/or fed virgin females in which vitellogenesis has not progressed and is released in females after feeding and mating. However, the characterization of EDSF and precise sites of production and storage await further investigation. PMID- 1738077 TI - Growth, development, pathogenicity, and transplantation of Echinostoma caproni (Trematoda) on the chick chorioallantois. AB - Excysted metacercariae of Echinostoma caproni were cultivated on the chorioallantoic membrane (CAM) of 6-day-old domestic chick embryos for 2-13 days postinoculation. There was no significant difference in the body area of fixed and stained preovigerous worms from the CAM versus those grown in domestic chicks. However, ovigerous worms from the CAM were significantly smaller than those from chicks. Worm development, i.e., gonadal differentiation, uterine curling, vitellinogenesis, ovigerousness, and oviposition, took 1 day longer on the CAM than in the chick. Histopathologic studies of worms attached to the CAM were done on cryostat and paraffin sections stained with hematoxylin and eosin. Some worms attached to the CAM by their collar spines and acetabulum, whereas others penetrated the chorionic epithelium and encapsulated in the mesenchyme. Pathogenicity to the CAM included hyperplasia of the chorionic epithelium, hemorrhagia, reduced fibrocytes and blood vessels, but increased lymphocytes and eosinophils in the mesenchyme. Attempts to transplant 11-day-old CAM worms to new CAMs were unsuccessful. PMID- 1738078 TI - Medical care costs of intravenous drug users with AIDS in Brooklyn. AB - This article reports on a study of medical costs of intravenous drug users (IVDUs) with acquired immune deficiency syndrome (AIDS) in Brooklyn, NY, U.S.A. Sociodemographic and clinical data as well as information on medical resource use was gathered for 38 IVDUs with AIDS, all of whom belonged to minority racial/ethnic groups and were covered by Medicaid insurance. Data obtained through patient interviews and review of medical records indicated that the sample had mean annual medical charges of $33,002 per patient per year. Average inpatient charges were $24,171, with an average of 1.13 hospitalizations and 38.5 days of in-hospital care. Significantly more in-hospital care and higher inpatient charges on average were noted among patients who did not have a stable housing environment. Outpatient charges averaged $8,831, with 80% for pharmaceuticals. This estimate of medical charges and resource use, one of the first developed in a cohort of nonwhite individuals with i.v. drug use as a risk factor for human immunodeficiency virus infection, is about one third less than recent estimates reported from studies of cohorts of white homosexual men. PMID- 1738079 TI - Circumstantial evidence of HIV transmission via breast milk. PMID- 1738080 TI - Design of active control equivalence trials. PMID- 1738081 TI - HIV transmission in simulated conditions of sharing hypodermic equipment. PMID- 1738082 TI - A low prevalence of HTLV-I/-II infection among eight population groups from Merida Yucatan, Mexico. PMID- 1738084 TI - HIV-1 and HIV-2 seroprevalence rates in mother-child pairs living in The Gambia (west Africa). AB - A seroepidemiological study was conducted, during 1988 and 1989, of mother-child pairs living in The Gambia (West Africa) in order to determine the distribution of the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2). Specimens were obtained from 931 children (age range, 14-17, months) and 923 mothers (age range, 14-17 years) using village-based cluster samples; the children are participating in The Gambia Hepatitis Intervention Study (GHIS), a large-scale HBV vaccination program. Large numbers of indeterminate Western blot patterns were observed among the mothers, mainly for HIV-1 antibodies; HIV-1 infected subjects were not found, whereas an HIV-2 seroprevalence rate of 0.75% was observed. The children born to the seven HIV-2 positive women were seronegative for HIV-2 antibodies, and none of the children showed HIV-2 or HIV-1 seropositively. PMID- 1738083 TI - Determinants of HTLV-1 seroprevalence in Miyazaki Prefecture, Japan: a cross sectional study. AB - To evaluate determinants of the prevalence of human T-cell leukemia virus type I (HTLV-I) antibody positivity in an endemic region, Miyazaki Prefecture, Japan, demographic and serologic data were collected on 7,055 individuals consecutively seen at Miyazaki City Health Promotion Center between September 1983 and December 1984. The overall HTLV-I seroprevalence was 8.5%; age and gender distributions of HTLV-1 antibody positivity were consistent with previous findings for endemic populations. The prefecture could be divided into two geographic areas based on seroprevalence: high prevalence (12.1%) in the southwest and medium prevalence (6.6%) for the rest of the prefecture. Current occupation in fishing, forestry, or livestock raising significantly correlated with HTLV-1 seropositivity [relative risk (RR) = 3.0, 2.5, 2.0, respectively]; farming also was associated but only in the medium prevalence region (RR = 1.3; p = 0.06). For a subset of 157 HTLV-I-positives and 175 negative controls screened for antibodies to the toxoplasmosis organisms, toxoplasma exposure was not significantly associated with HTLV-I infection. In this endemic Japanese population, both geographic and sociologic factors characterized the distribution of HTLV-I seroprevalence, reflecting transmission patterns and historical duration of the infection. PMID- 1738085 TI - Lack of evidence of vertical transmission of human immunodeficiency virus type 2 in a sample of the general population in Bissau. AB - Twenty-nine human immunodeficiency virus type 2 (HIV-2) seropositive women identified in a cross-sectional study in Bissau in 1987 participated in a follow up study in 1988, where each was matched for age and marital status with two HIV 2 seronegative women. Detailed information about all pregnancies was obtained. The HIV-2 seropositive women and their controls had similar mean numbers of pregnancies, live children, children who died, and abortions. The HIV-2 seropositive women did not have a greater risk of having had an abortion or a child who died than did the HIV-2 seronegative women. No difference in survival was seen between children born to HIV-2 seropositive and HIV-2 seronegative women. The H/S-ratios and CD4 numbers were lower in the seropositive group, but none had values lower than 0.4 and 0.4 x 10(9)/L, respectively. Seven prospectively observed children born to HIV-2 seropositive mothers showed no sign of infection. The lack of evidence of transmission of HIV-2 from mother to child is suggested to be due to the absence of marked immunodeficiency in this random sample of the general population. PMID- 1738086 TI - HLA-B35 is associated with accelerated progression to AIDS. AB - To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (HIV) infection, we performed (a) a case control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8 lymphocytosis syndrome. In the case control study, there was a significantly higher frequency of HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of HLA-B35 in individuals with the diffuse infiltrative lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in HIV infection in which a low rate of progression to opportunistic infections was found. The high rate of salivary and lacrimal gland lymphoma in this group suggests that there is dissociation between the presence of HLA-B35 and the development of particular AIDS-defining conditions. We conclude that HLA-B35 is a risk factor for more rapid progression to AIDS, particularly opportunistic infections and Kaposi's sarcoma, operating in groups with high rates of newly acquired HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738087 TI - Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration. AB - Quantification of human immunodeficiency virus (HIV) proviral DNA in peripheral blood mononuclear cells (PBMC) was performed in 13 HIV-seropositive asymptomatic individuals during 10-24 months by polymerase chain reaction amplification of multiple half-log dilutions of cellular DNA. At enrollment, subjects had a geometric mean titer of 100 copies of HIV provirus per 10(6) PBMC (mean +/- SD, 2 +/- 0.9 log10). In four untreated individuals there was no significant change in provirus levels during a mean period of 13.3 months. In eight patients treated with zidovudine (ZDV) and human recombinant interleukin 2 (rIL-2), HIV provirus copies declined to 13 per 10(6) cells (1.1 +/- 0.8 log10) at the end of the first course of ZDV and rIL-2 at week 20 (p less than 0.01), and to 40 per 10(6) cells (1.6 +/- 0.9 log10) after 12 months of treatment (p less than 0.04). Subsequent courses, which included 12 weeks of ZDV alone or 4 weeks of IL-2 alone, did not significantly change the already depressed provirus copy numbers. Proviral copy number also remained depressed during drug-free "washout periods" between courses. Finally, we observed a return to a geometric mean of 400 copies per 10(6) cells (2.6 +/- 0.3 log10) a mean of 7.9 months after discontinuation of therapy. Measurement of changes in HIV provirus should provide a direct marker for defining antiviral activity of drugs, biologics, and combination therapy. PMID- 1738088 TI - A comparison of HIV-1 antibody classes, titers, and specificities in paired semen and blood samples from HIV-1 seropositive men. AB - Twenty-eight paired blood and semen samples obtained from human immunodeficiency virus type 1 (HIV-1) seropositive men at various stages of disease progression were evaluated for titer and immunoglobulin (Ig) class by an enzyme-linked immunosorbent assay (ELISA). Blood antibody titers ranged from 40,000 to 4,000,000 with a median of 40,000. Semen titers ranged from 400 to 40,000 with a median of 400. HIV-1 antibody titers in matched semen and blood samples showed a strong positive correlation (r = 0.963). The ratio of semen:blood titers ranged from 1:1000 to 1:10 with a median of 1:100. There was no correlation between blood or semen antibody titer and stage of disease of the patients. However, there was a trend toward higher (greater than or equal to 4000) semen antibody titers in men with evidence of genital tract inflammation greater than 10(6) white blood cells/ml semen; 3/5 versus 5/23, p greater than 0.1 Fisher exact test). All HIV-1 antibodies detected were of the IgG class; no IgA or IgM class antibodies of titers greater than or equal to 40 were found in either blood or semen. Thirteen paired blood and semen samples from individual patients were analyzed for antibody specificity by Western blot. In some cases antibody profiles in semen were different from those in blood; strong antibody reactivity against the gp160 viral coat antigen band was consistently detected in semen and blood, whereas the prevalence of detectable antibody reactivity against the p55 and p17 HIV-1 antigen bands was significantly reduced in semen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738089 TI - Premarital HIV-1 testing in New Jersey. AB - To answer questions related to the usefulness of premarital testing for human immunodeficiency virus type 1 (HIV-1), two "blinded" or "nonlinked" HIV-1 serosurveys were done in New Jersey, a state with a high incidence of AIDS, on blood specimens submitted for a premarital serologic test for syphilis. The first survey involved premarital blood specimens submitted to the New Jersey Department of Health laboratory for the year starting September 1987. The second survey involved premarital specimens submitted to five private or hospital clinical laboratories in the spring of 1989, of which approximately 1,000 consecutive premarital specimens from each laboratory were sent to the Department of Health laboratory for HIV-1 testing. Of 4,247 specimens tested in the 1987-1988 survey, 21 (0.49%) were positive for antibodies to HIV-1, while among 4,696 specimens in the 1989 survey, 29 (0.62%) were positive. When the survey results were weighted by the number of marriages by geographic regions of the state, the weighted premarital HIV-1 seroprevalence was 0.55% for the 1987-1988 survey and 0.62% for the 1989 survey. The male/female ratio of positive tests was 2.7:1 in 1987-1988 and 1.6:1 in 1989. Of the 8,943 specimens in both surveys, 5 (0.06%) gave an indeterminate immunoblot result, compared with 50 positive results. These percentages of premarital HIV-1 infections are much higher than earlier estimates and reports and are of the same magnitude as recently reported blinded premarital HIV-1 testing elsewhere. Results of this magnitude support a recommendation in New Jersey of voluntary HIV-1 counseling and testing for marriage applicants. PMID- 1738090 TI - Activity of CD4-Pseudomonas exotoxin against cells expressing diverse forms of the HIV and SIV envelope glycoproteins. AB - CD4(178)-PE40 is a genetically engineered hybrid toxin containing a portion of human CD4 linked to the translocation and ADP-ribosylation domains of Pseudomonas exotoxin A. In vitro, the molecule has been shown to selectively kill cells expressing the envelope glycoproteins of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV), and to inhibit HIV spread. In this report we examine the activity of the hybrid toxin against cells expressing diverse forms of the HIV and SIV envelope glycoproteins, encoded by recombinant vaccinia virus vectors. The activity of CD4(178)-PE40 was found to be unaffected by mutations in the HIV-1 or HIV-2 envelope glycoprotein genes, which prevent normal proteolytic processing of the corresponding gp160 precursor molecules. Cells expressing a mutant HIV-1 envelope glycoprotein lacking most of the cytoplasmic tail of the gp41 transmembrane subunit were also sensitive to the hybrid toxin. Most interestingly, HIV-1, HIV-2, and SIVmac envelope glycoprotein molecules known to have widely differing affinities for CD4 were found to be comparably effective at mediating sensitivity to CD4(178)-PE40. By virtue of its ability to kill infected cells, the hybrid toxin inhibited the spread of SIVmac in vitro. These results indicate that CD4(178)-PE40 is active against cells expressing HIV and SIV envelope glycoproteins with a diverse array of structural differences. PMID- 1738091 TI - Contribution of disulfide bonds in the carboxyl terminus of the human immunodeficiency virus type I gp120 glycoprotein to CD4 binding. AB - The carboxyl half of the HIV-1 gp120 glycoprotein, which has been implicated in binding to the CD4 receptor, contains two disulfide bonds linking cysteine residues 378-445 and 385-418. To examine the necessity of these disulfide bonds for the formation and/or maintenance of a gp120 glycoprotein competent for CD4 binding, we created mutants of a soluble form of gp120 in which combinations of these cysteine residues were altered. The mutant glycoproteins were examined for export from the expressing cell and for CD4 binding ability. Mutant gp120 molecules lacking both disulfide bonds were not stably expressed or exported. However, mutants for which either disulfide bond could form were exported and were fully competent for CD4 binding. In some cases, the presence of one of the pair of linked cysteines exerted more detrimental effects on export or CD4 binding than did alteration of both cysteines. Thus, the evaluation or the contribution of a particular disulfide bond to a phenotype should include studies in which both cysteines involved in the bond are simultaneously altered. PMID- 1738092 TI - HIV-1 infection of human fetal thymocytes. AB - Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions. PMID- 1738093 TI - Age-dependent gentamicin experimental nephrotoxicity. AB - The nephrotoxic potential of gentamicin was compared in adult (2-month-old) and old (24-month-old) female Sprague-Dawley rats in a model of short-term infusion. Animals were infused over a 12-hr period with saline or with gentamicin achieving steady-state serum levels of 56.1 +/- 11.7 (n = 18) and 59.8 +/- 14.7 (n = 17) micrograms/ml +/- S.D. (N.S.) in the adult and the old rats, respectively. Animals were sacrificed 2 hr (day 0), 4 days and 8 days after the end of the infusion. The renal cortical levels of gentamicin at day 0 (2 hr after the end of the infusion) were 1161 +/- 120 and 1125 +/- 275 micrograms/g of tissue +/- S.D. (N.S.) in the adult and the old rats, respectively. Tissue levels of gentamicin were lower in both gentamicin-treated groups on day 4 and 8 as compared with day 0 (P less than .05). The sphingomyelinase activity (measure of the lysosomal phospholipidosis) was significantly inhibited in the renal cortex of the adult and the old rats, but no significant difference was observed between these two groups. The in vivo [3H]thymidine incorporation into DNA, expressed as the percentage of the values measured in each age-matched control group, was significantly lower in the old animals as compared with that measured in the adult rats (P less than .05). No significant difference was observed in the renal function of adult rats, but a significant increase in the serum creatinine levels was measured in the old rats on day 4 of the experiment (248% of the control value, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738094 TI - Renal and antihypertensive effects of a novel eukalemic diuretic, ICI 207,828. AB - ICI 207,828, an aminomethylphenol pyrazine derivative, produces water diuretic effects with only minimal alterations in kaliuresis in dogs and rats after oral and parenteral administration. In the dog, ICI 207,828 reached maximum activity at a dose of 10 mg/kg, p.o. This was comparable to that of hydrochlorothiazide (HCTZ) at a dose of 5 mg/kg, p.o. or higher. In the rat, a dose of 30 mg/kg, p.o. of ICI 207,828 was comparable to the maximum of water diuretic and saluretic response obtained with HCTZ at a dose of 10 mg/kg, p.o. Based upon studies using in vitro amphibian models of the mammalian nephron, ICI 207,828 appeared to act on both the thick ascending limb of the loop of Henle and the late distal nephron. In the toad bladder preparation, ICI 207,828 inhibited Na+ transport when placed on either the mucosal (amiloride-like) or serosal (thiazide-like or loop diuretic-like) sides. This compound also inhibited Cl- transport in the toad cornea preparation (loop diuretic-like). ICI 207,828 did not change plasma K+ significantly in dogs dosed for 14 days at doses having diuretic effects (5 and 10 mg/kg, p.o., daily). In contrast, HCTZ consistently decreased plasma K+, whereas amiloride increased it significantly. ICI 207,828 demonstrated antihypertensive effects in spontaneously hypertensive rats. At 30 mg/kg, p.o., b.i.d., ICI 207,828 and HCTZ produced approximately equal antihypertensive activities during a 3 1/2-day treatment period. The pharmacological profile of ICI 207,828 indicates that this compound is a potent eukalemic diuretic and antihypertensive agent in animals. PMID- 1738095 TI - Evaluation of the renal site of action of a novel, eukalemic diuretic, ICI 207,828. AB - ICI 207,828 is a novel eukalemic diuretic in animals that is comparable in effect to hydrochlorothiazide. We used micropuncture and microperfusion techniques to determine the site(s) of action of this compound in the rat nephron. Either furosemide (FUR) or ICI 207,828 were perfused through the loop of Henle in situ. Both compounds caused significant reduction in water and electrolyte reabsorption by the loop. The effect of ICI 207,828 was significantly less than that of FUR. Both amiloride and ICI 207,828 were perfused, in situ, through the superficial distal tubule. ICI 207,828 had an effect similar to amiloride. Sodium and water reabsorption and potassium secretion were inhibited. In free-flow micropuncture studies, ICI 207,828, infused continuously i.v., had little effect on electrolyte and water reabsorption by the superficial proximal tubule. This compound significantly inhibited water and electrolyte reabsorption by the loop of Henle. Distal tubule secretion of potassium was inhibited. In addition, fractional potassium reabsorption beyond the superficial, late distal tubule was inhibited by ICI 207,828. From these results, we conclude that ICI 207,828 significantly inhibits electrolyte and water transport by the loop of Henle and distal tubule, and at sites beyond the superficial distal tubule such as either the collecting duct system or juxtamedullary nephrons. The reduction in distal potassium secretion, in concert with reduced loop of Henle and postdistal reabsorption, results in no net potassium loss in the urine, thus rendering this compound eukalemic. PMID- 1738096 TI - Effect of chronic ethanol diet on expression of gonadotropin genes in the male rat. AB - The present study elucidates further the defect in the function of hypothalamic pituitary-gonadal axis in the male rat after a 6% ethanol diet for 5 weeks. The body, testis, prostate and seminal vesicle weights of the ethanol-treated animals did not differ from those of the pair-fed controls. However, the weights of the ethanol and pair-fed groups were significantly lower than in untreated controls (P less than .001). The pituitary luteinizing hormone beta mRNA level of ethanol treated rats was significantly higher (P less than .05) but the follicle stimulating hormone beta mRNA level was lower (P less than .05) than those of the diet control group. Additionally, the follicle-stimulating hormone beta mRNA level of the diet controls was higher than that of the untreated controls (P less than .05). There were no significant differences in the levels of common-alpha subunit or prolactin mRNA between the groups. The serum and testicular testosterone concentrations of the ethanol and diet control groups did not differ, but both were significantly lower than in untreated controls (P less than .01). The serum luteinizing hormone of ethanol rats was significantly higher than that of diet controls (P less than .01), but the pituitary luteinizing hormone, the serum and pituitary follicle-stimulating hormone and the prolactin of ethanol and diet control animals did not differ. PMID- 1738097 TI - H+ coupled active transport of bestatin via the dipeptide transport system in rabbit intestinal brush-border membranes. AB - Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine], a dipeptide containing an unusual amino acid, has been used clinically as an anticancer agent in p.o. dosage form. We examined the transport characteristics of [3H]bestatin by rabbit intestinal brush-border membrane vesicles. Bestatin uptake was stimulated by an inward H+ gradient (overshoot phenomenon) and by an interior-negative membrane potential. About half of the apparent bestatin uptake at 1 mM by brush border membrane vesicles was estimated as binding to the membranes. The affinity constant for the bestatin transport was 0.52 mM. The uptake of bestatin by brush border membrane vesicles was inhibited by p.o. cephalosporins and dipeptides, but not by amino acids. In vesicles preloaded with either bestatin, cephradine or glycylsarcosine, the uptake of [3H]bestatin was stimulated markedly (countertransport effect). These results indicate that bestatin is transported via the H+/dipeptide transport system in rabbit intestinal brush-border membranes. PMID- 1738098 TI - Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction. AB - Ketoconazole is commonly used in patients with fungal infections during immunosuppressive therapy with prednisolone. Ketoconazole inhibits mixed function oxidases, enzymes responsible for the catabolism of prednisolone, and might, by that mechanism, increase prednisolone concentrations and thus, the immunosuppressive effect of prednisolone. On the other hand, ketoconazole has been found to bind to the glucocorticoid receptor and, thereby, to function as a glucocorticoid antagonist in cultured cell preparations. In order to establish whether ketoconazole enhances or attenuates the immunosuppressive effect of prednisolone, the influence of ketoconazole on the kinetics of prednisolone and on the delayed hypersensitivity response was assessed in mice. Ketoconazole increased prednisolone concentrations, measured by high pressure liquid chromatography, in mice given a single dose of prednisolone or a continuous prednisolone treatment for 17 days. At four different doses of prednisolone administered for 17 days, the glucocorticoid therapy-associated inhibition of the delayed hypersensitivity response to keyhole limpet hemocyanin was enhanced by ketoconazole. Thus, coadministration of ketoconazole with prednisolone increases the exposure to the steroid and enhances the immunosuppressive effect. PMID- 1738099 TI - Effect of benzylpenicillin on the disposition of cefodizime in rats: no net effect on total clearance due to decreased hepatobiliary clearance and increased renal clearance. AB - Effect of benzylpenicillin (PCG) on the disposition of [14C]cefodizime (CDZM), a nonmetabolizable analog of cefotaxime, was studied in rats. Rats were divided into two groups to receive i.v. injection of [14C]CDZM (15 mg/kg) alone and during the infusion of PCG. Although the total concentration of [14C]CDZM in plasma vs. time data were almost the same between the groups, the unbound concentration of [14C]CDZM was increased 2-fold by the treatment with PCG. Hepatobiliary excretion of [14C]CDZM was reduced by the treatment with PCG, indicating that PCG inhibits the transport of CDZM across the sinusoidal and/or bile canalicular membrane(s). Further support for this hypothesis is the finding that the uptake of [14C]CDZM by the isolated hepatocytes in vitro was via an active transport process that was reduced by PCG. Furthermore, pharmacokinetic analysis of the data obtained from in vivo and in vitro experiments indicated that PCG reduced the permeability of [14C]CDZM across the sinusoidal and bile canalicular membranes to 32% and 40% of the control value, respectively. The urinary excretion of [14C]CDZM was principally via the glomerular filtration process and was not affected by the treatment with PCG. Because of the 2-fold rise in the unbound fraction of [14C]CDZM in the treated rats, the renal clearance for total [14C]CDZM was increased 2-fold by the treatment with PCG. The increase in the renal clearance compensated for the decrease in the hepatic clearance. The net effect of the alterations in these pharmacokinetic parameters resulted in no change in the time profiles of [14C]CDZM concentration in plasma between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738100 TI - Reduced glomerular hypertrophy by somatostatin analog, SMS 201-995, in the subtotal nephrectomized rats fed high-protein meals. AB - The chronic effects of SMS 201-995 (SMS), a long-acting somatostatin analog, on the progression of renal failure in 3/4 subtotal nephrectomized rats (NPX) fed high protein meals (40% protein) were investigated. Rats were divided into four groups, [i.e., normal control (C) (n = 6), NPX control (NPX-C) (7), NPX treated with SMS 1.0 micrograms/day (SMS-1.0) (7) and SMS-10.0 (7)]. SMS was continuously administered s.c. via an osmotically driven pump for 8 weeks. SMS had no significant changes in either body weight or hematocrit levels for NPX groups. Systolic blood pressure in NPX rats showed similar elevations, but SMS had no distinct effect on it for them. Significant changes in urine volume, creatinine clearance, and urinary protein excretion were not obtained among the NPX rats. No significant changes of glomerular sclerosis index was found among the NPX rats. Mean planar area of glomeruli in NPX rats was significantly larger than in normal control rats. NPX treated with both 1.0 and 10.0 micrograms/day SMS had statistically smaller values compared with NPX control rats. It was concluded that the chronic administration of SMS reduced glomerular hypertrophy without altering renal functions in this experimental model. PMID- 1738101 TI - Mechanisms of vomiting induced by serotonin-3 receptor agonists in the cat: effect of vagotomy, splanchnicectomy or area postrema lesion. AB - The locations of serotonin-3 (5-HT3) receptors involved in initiating vomiting (emesis) were assessed by cutting visceral afferents or lesioning the area postrema. The 5-HT3 receptor agonists phenylbiguanide (PBG) and 2-methyl-5-HT were shown to induce vomiting and related prodromal signs (e.g., licking, swallowing) in nonoperated cats. Two-methyl-5-HT, but not PBG, also usually produced defecation and sometimes urination. Most studies were conducted using PBG, which induced vomiting in 40/49 (82%) cats at doses of 8.0 mg/kg i.p. or less (thresholds ranged from 2-8 mg/kg, median 5 mg/kg). Latencies to the first episode ranged from 4 to 21 min (median 7.5 min). PBG-induced vomiting was blocked by the 5-HT3 receptor antagonist MDL 72222. Lesions of the area postrema had no apparent effect on vomiting induced by PBG or by electrical stimulation of abdominal vagal afferents. In contrast, the threshold of PBG-induced vomiting was increased by supradiaphragmatic vagotomy and greatly increased by splanchnic nerve section. Thus, abdominal visceral afferents, but not the area postrema, play an important role in mediating vomiting induced by i.p. injection of the 5 HT3 receptor agonist PBG. The mechanisms by which vomiting is induced by PBG as compared to the cancer chemotherapeutic drug cisplatin are discussed. PMID- 1738102 TI - Time-dependent protective effects of calcium channel blockers on anoxia- and hypoxia-induced proximal tubule injury. AB - The effects of anoxia or hypoxia on Ca++ uptake and lactic dehydrogenase (LDH) release were examined in freshly isolated rat proximal tubules (rPT). Both Ca++ uptake and LDH release were increased above control after only 10 min of either anoxia or hypoxia in rPT. The increase in Ca++ uptake was through voltage sensitive, slow Ca++ channels, because pretreatment with chemically dissimilar calcium channel blockers (CCB), either verapamil or flunarizine, prevented the increased Ca++ uptake and reduced the LDH release from the anoxic and hypoxic rPT. After 20 min of hypoxia, however, verapamil pretreatment did not significantly reduce the high Ca++ uptake rate, thus, suggesting that this increase in Ca++ permeability was occurring through pathways other than the slow Ca++ channels. The increase in LDH release was only slightly decreased by verapamil after 20 min of hypoxia. After 20 min of anoxia in rPT, Ca++ uptake was no longer increased, but the increased LDH release persisted. These effects of anoxia were unaltered by verapamil. These results, thus, suggest that early membrane injury to isolated rPT in suspension, which is associated with 10 min of either anoxia or hypoxia, involves increased cellular Ca++ uptake through voltage sensitive Ca++ channels and protection is afforded by CCB. In contrast, after 20 min of anoxia or hypoxia, rPT membrane damage persisted and was only partially reversed by CCB. The rPT injury induced by 20 min of O2 deprivation, thus, involves factors independent of voltage-sensitive Ca++ channels. PMID- 1738103 TI - Effects of fluoxetine on convulsions and on brain serotonin as detected by microdialysis in genetically epilepsy-prone rats. AB - Fluoxetine, an antidepressant and inhibitor of serotonin reuptake, was evaluated as an anticonvulsant in genetically epilepsy-prone rats (GEPRs) because seizure predisposition in GEPRs is partially dependent on deficits in brain serotonin. Fluoxetine produced dose-dependent reductions in sound-induced convulsion intensity in both moderate seizure GEPRs and severe seizure GEPRs with the peak anticonvulsant effect occurring 4 hr after i.p. administration. A subchronic study in severe seizure GEPRs demonstrated that the ED50 after 28 days of dosing (8.2 mg/kg) was lower than the acute ED50 (15.9 mg/kg) so that there was no apparent development of tolerance. The lower ED50 after subchronic administration apparently resulted from accumulation of fluoxetine and its metabolite norfluoxetine in brain. Brain microdialysis studies showed that acute fluoxetine administration resulted in a significant increase in extracellular serotonin concentration in the thalamus. The increase in serotonin concentration in the dialysate corresponded temporally with the anticonvulsant effect produced by fluoxetine. Intrathalamic administration of fluoxetine via the dialysis probe caused an increase in serotonin concentration in the dialysate, suggesting that the effect of fluoxetine was on nerve terminals. Fluoxetine could be dialyzed from thalamus after its i.p. administration. Fluoxetine concentration in the thalamic dialysate was similar to the concentration found in plasma. We conclude that fluoxetine is an effective anticonvulsant in GEPRs and that the microdialysis results strongly suggest a relationship between the effects of fluoxetine on serotonergic neurons and the anticonvulsant effect produced by this drug. PMID- 1738104 TI - Endothelium-dependent nonadrenergic, noncholinergic neural relaxation in guinea pig pulmonary artery. AB - The presence and the possible mechanism of action of the inhibitory nonadrenergic, noncholinergic nerve system (i-NANC) were investigated in guinea pig pulmonary artery (PA) precontracted with U44069 (a thromboxane analog). In the presence of alpha adrenergic blockage, electrical field stimulation induced a frequency-dependent, tetrodotoxin-sensitive relaxation. This relaxation was reduced by 9.1 +/- 1.9 and 19.4 +/- 2.8% by atropine (1 microM) and combined atropine and propranolol (both 1 microM), indicating that the main component is mediated by i-NANC neural mechanisms. In the branch PA rings, this i-NANC relaxation was unaffected by pretreatment with a cyclooxygenase inhibitor (indomethacin, 10 microM), 5-lipoxygenase inhibitor (A63162, 1 microM) or substance P desensitization, but was inhibited markedly by the P2y-purinoceptor antagonist reactive blue 2 (30 microM) and slightly potentiated by the peptidase alpha-chymotrypsin (2 U/ml). L-NG-monomethyl-arginine(L-NMMA), a nitric oxide synthesis inhibitor, caused a concentration-dependent inhibition of the i-NANC relaxation (53.9 +/- 4.1% at 100 microM), but had no effect on equivalent nitroprusside-induced relaxation. The inhibitory effect of L-NMMA was reversed completely by L-arginine (300 microM), but not by D-arginine (300 microM). Removal of vascular endothelium greatly reduced the i-NANC relaxation in the branch PA rings, but had no effect on i-NANC relaxation in main PA rings. Both in vivo capsaicinization and in vitro desensitization with capsaicin (1 microM) caused a significant reduction of the i-NANC relaxation in main PA, but had no significant effect in the branch PA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738105 TI - Effect of endothelin-1 on guinea pig gallbladder smooth muscle in vitro. AB - The purpose of this study was to investigate the pharmacological activity of endothelin-1 (ET-1) on guinea pig gallbladder smooth muscle. Guinea pig gallbladder muscle strips were mounted in 10-ml siliconized organ baths containing Krebs' solution. After 1 hr of equilibration, ET-1 was added cumulatively. ET-1 induced slow-developing and long-duration contractile responses. The EC50 was approximately 10 nM. ET-1 was 5 times less potent than cholecystokinin (EC50, 2 nM), but 20 and 40 times more potent than carbachol (EC50, 200 nM) and histamine (EC50, 400 nM), respectively. The concentration response curve to ET-1 was not affected by tetrodotoxin (0.1 microM) or by the muscarinic antagonist, atropine (10 microM). The neuronal N-type calcium channel blocker, omega-conotoxin (0.1 microM), had no significant effect on the ET-1 concentration-response curve. In contrast, the contractile effect to ET-1 was reduced markedly by removal of extracellular calcium or by the voltage-dependent calcium channel blockers nicardipine and diltiazem. Substitution of strontium (an inhibitor of intracellular calcium release) for Ca++ significantly reduced the response to ET-1. The cyclooxygenase inhibitor indomethacin had no significant effect on the contractile activity of ET-1. These finding suggest that ET-1 is a potent contractile stimulant of guinea pig gallbladder and that it acts directly on the smooth muscle. The activity depends on extracellular Ca++, suggesting involvement of Ca++ influx via the voltage-dependent Ca++ channel and on intracellular calcium. PMID- 1738106 TI - Role of electronic factors in binding and reduction of azo dyes by hepatic microsomes. AB - The factors which regulate the binding and reduction of azo dyes by rat liver microsomes have been investigated. Azo dyes having both electron-donating and withdrawing substituents were reduced more readily both enzymically and chemically (dithionite) than those containing electron-donating substituents alone, which is consistent with less negative oxidation-reduction potentials of the former. A linear correlation between Vmax and Km was seen for substrates having only electron-donating substituents, suggesting a possible inverse relation between binding affinity and rate of reduction. This relationship was not apparent for substrates having both electron-donating and -withdrawing substituents. A lower Km was seen with substrates having a greater number of heteroatoms bearing nonbonding electrons in either electron-donating or withdrawing groups. Furthermore, more basic dyes, which have a higher density of nonbonding electrons, showed an inverse correlation with both Vmax and Km. The requirement of nonbonding electrons was also observed with the binding of the fully reduced amine metabolites to microsomal cytochrome P-450. Type II binding spectra were observed for both aniline and 4-chloroaniline, but not with aniline derivatives bearing electron-withdrawing substituents such as methyl anthranilate and methyl-4-aminobenzoate. Electron-withdrawing substituents increase delocalization of nonbonding electrons on the amino residue; consequently, these are no longer available for binding to the enzyme. The binding constant of the reduced metabolite, aniline (36 microM), relative to the Km values of substrate azo dyes (range 0.31-1.73 microM) implies that the more weakly bound amine metabolites are readily released from the binding/catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738107 TI - Heroin, 6-acetylmorphine and morphine effects on threshold for rewarding and aversive brain stimulation. AB - Studies investigating the reinforcing and analgesic activity of heroin and morphine have found that heroin is a more potent compound. The rapid deacetylation of heroin to 6-acetylmorphine and morphine raises questions concerning the underlying mechanism responsible for this difference in potency. The present series of experiments addressed this issue by examining, in the rat, the relative potency of heroin and its active metabolites, 6-acetylmorphine and morphine, to lower the threshold for rewarding stimulation of the medial forebrain bundle and raise the threshold for aversive stimulation of the mesencephalic reticular formation. Reward and escape thresholds were determined by using a modification of the psychophysical method of limits. Heroin was found to be approximately 40 times more potent than morphine in lowering the reward threshold and approximately 6.5 times more potent in raising the escape threshold. 6-Acetylmorphine and heroin were approximately equipotent in producing significant effects on the threshold for both rewarding and aversive brain stimulation. These findings suggest that heroin's increased potency when compared to morphine may be due, in part, to the activity of 6-acetylmorphine. PMID- 1738108 TI - Cocaine and metabolite concentrations in the fetal guinea pig after chronic maternal cocaine administration. AB - To determine the disposition of cocaine (COC) and metabolites after chronic COC exposure in the late gestation guinea pig, six time-bred Dunkin-Hartley guinea pigs were given 10 daily 6 mg/kg COC s.c. injections from day 50 of gestation. Maternal blood and urine, fetal cord blood, and brain and amniotic fluid were collected 1 hr after the last injection. There was no difference between maternal and fetal plasma COC concentrations. This may be due to the combined effect of lower protein binding and ion trapping of COC in the fetus. Benzoylecgonine was higher in maternal plasma, but benzoylnorecgonine was higher in fetal plasma. COC brain-to-plasma ratios were similar in the dam and fetus. Benzoylecgonine was the only metabolite that could be detected in the brain, but levels were too low to quantitate. COC accumulated 3 to 4 times plasma concentrations in the amniotic fluid and was directly proportional to fetal plasma COC concentrations. Benzoylnorecgonine in amniotic fluid accumulated to 2 times fetal plasma levels. The in vitro half-life of COC in amniotic fluid was 30 times longer than plasma elimination half-life in vivo. The high level and long duration of COC in amniotic fluid serve as a reservoir for prolonged fetal COC exposure. PMID- 1738109 TI - Purinergic relaxation and hyperpolarization in guinea pig and rabbit coronary artery: role of the endothelium. AB - Purinergic relaxation and hyperpolarization was investigated in the isolated guinea pig coronary artery (GPCA) and compared to purinergic relaxation in the rabbit coronary artery (RCA). Vessels were contracted with the histamine H1 receptor agonist 2-(2-aminoethyl)pyridine (AEP) and the actions of adenosine, AMP, ATP, 2-chloroadenosine (CIAD),2-methylthioATP (MeATP) and beta,gamma methylene ATP compared. The order of potency with P1 agonists in GPCA was CIAD greater than adenosine = AMP and for P2y agonists it was MeATP greater than ATP greater than beta,gamma-methylene ATP. Both ATP and CIAD produced less relaxation of GPCA segments contracted with K+ (36-100 mM) than with AEP. The IC50 for CIAD, but not ATP, was increased in the GPCA with 8(p-sulfophenyl)theophylline (100 microM). Relaxations with ATP and CIAD were not different in endothelium-denuded GPCA. Methylene blue (50 microM) increased AEP contractile amplitude by 33% and increased the IC50 values for both CIAD and ATP. A similar shift in potency to purines was seen by varying AEP concentration. ATP, CIAD and MeATP also relaxed RCA. These responses were not different in endothelium-denuded vessels. Pressure application of ATP, MeATP, adenylylimidodiphosphate and to a lesser extent beta,gamma methATP transiently hyperpolarized cells in the GPCA, whereas CIAD did not. ATP hyperpolarization was enhanced in the presence of AEP and abolished after endothelium removal. The results indicate that purinergic relaxation in the GPCA and RCA is mediated by both P1 and P2y receptors located on the smooth muscle cells. In the GPCA, P1 receptors appear limited to the muscle, whereas P2y receptors are present on both muscle and endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738110 TI - Evidence of significant absorption of antipyrine from urinary bladder of rats. AB - We examined the in vivo absorption and pharmacokinetics of antipyrine, a base that is unionized at physiologic pH, from the urinary bladder of adult female Fischer rats. The clearance of an i.v. dose of antipyrine (25 mg/kg) was found to vary considerably between animals, which is consistent with the literature data. Therefore, it was necessary to simultaneously determine drug clearance and bladder absorption in the same animal. This was accomplished by giving concomitantly an i.v. dose of [14C]antipyrine (2.5 muCi, about 90 micrograms/kg) via a jugular vein catheter and an intravesical dose of unlabeled antipyrine (33 mg/kg) via a urethral catheter. Unlabeled antipyrine was detected in plasma, indicating the absorption of antipyrine into systemic circulation. The bioavailability of the intravesical dose was calculated using the clearance of [14C]antipyrine and the plasma concentrations of unlabeled antipyrine. The intravesical dose was withdrawn through the urethral catheter after 90 min. To minimize mechanical manipulation and damage, the bladder was not rinsed. This may have caused the incomplete recovery of the unabsorbed dose; about 65 +/- 18% (mean +/- S.D.) of the dose was recovered at 90 min. Maximal plasma concentrations were achieved at 10 to 48 min after removal of the intravesical dose, which is consistent with a continued absorption of the residual dose. The intravesical bioavailability was variable between animals, with an average of 11.6 +/- 6.4% (mean +/- S.D.; range, 4.1-19.2%). In conclusion, these data demonstrate that neutral drugs such as antipyrine are absorbed from the bladder, that the extent of absorption is variable and that the urinary bladder may be a site of significant re-entry of drugs into the systemic circulation. PMID- 1738111 TI - Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release. AB - The aim of the present study in rat spinal cord synaptosomes was to compare the pharmacological characteristics of the serotonin (5-HT)1B receptor defined by [125I]iodocyanopindolol [( 125I] ICYP) binding and the 5-HT autoreceptor defined by inhibition of [3H]-5-HT release. In Percoll gradient Fractions 3 and 4 of spinal cord synaptosomes, a single saturable binding site for [125I]ICYP with a maximum binding of 70 and 134 fmol/mg, respectively, was demonstrated in the presence of 30 microM isoproterenol. The Kd of 0.16 nM did not vary between fractions. Competition for [125I]ICYP binding by various 5-HT agonists and antagonists also indicated a single site model based on a Hill coefficient of approximately 1.0. The most potent compounds at displacing [125I]ICYP binding were RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole), 5 carboxyamidotryptamine HCl, 5-methoxytryptamine, 5-HT and CGS 12066B (7 trifluoromethyl-4(4 methyl-1-pyrolo[1,2-a]-quinoxaline malate). [125I]ICYP binding was not altered by compounds with activity at 5-HT1A, 5-HT1C, 5-HT2, 5 HT3 or alpha-2 receptor sites. Similar to the pharmacological characteristics of the 5HT1B site defined by [125I]ICYP, compounds most active at inhibiting 15 mM K(+)-stimulated release of [3H]-5-HT were RU24969 = 5-carboxyamidotryptamine HCl = CGS 12066B greater than 5-methoxytryptamine greater than 5-HT. Compounds with activity at 5-HT1A, 5-HT1C, 5-HT2 or 5-HT3 sites were inactive. A correlation analysis of selective 5-HT1B compounds comparing the pKD for displacement of [125I]ICYP vs. the IC50 for inhibition of [3H]-5-HT release demonstrated the pharmacological similarity of the presynaptic inhibitory 5-HT autoreceptor and the 5-HT receptor site defined by [125I]ICYP binding in spinal cord synaptosomes (r = 0.791, P = .0193). Although [125I]ICYP binding was unaltered, alpha-2 agonists such as clonidine, norepinephrine and UK 14304 [5-bromo-6-[2-imidazolin 2-ylamino]-quinoxaline) as well as the alpha-2 antagonists rauwolscine and yohimbine also decreased the K(+)-stimulated release of [3H]-5-HT and phentolamine, an alpha-2 antagonist increased release. The action of these alpha 2 compounds to alter [3H]-5-HT release suggests the presence of heteroreceptors localized on 5-HT terminals in the spinal cord. These results point out that [125I]ICYP identifies the 5-HT1B receptor, and affinity of compounds for this site predicts action at the 5-HT1B autoreceptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1738112 TI - Coronary blood flow in rats is dependent on the release of vascular nitric oxide. AB - The present study evaluated the role of nitric oxide (NO) in determining basal coronary vascular tone and the mechanism by which NO regulates coronary blood flow. Sprague-Dawley rats were anesthetized and instrumented for recording arterial pressure (AP), heart rate (HR) and coronary blood flow (CBF; Doppler). In rats without ventricular pacing, N-nitro-L-arginine methyl ester (LNAME) (10 mumol/kg, i.v.), an inhibitor of NO synthesis, produced an increase in AP and a decrease in HR. The LNAME-induced bradycardia was inhibited by sinoaortic denervation. LNAME also produced a reduction in left anterior descending (LAD) CBF. When the same dose of LNAME was administered to a separate group of rats measuring CBF in the right coronary artery (RCA), the decrease in CBF was found to be more prominent in the LAD compared to the RCA. Removal of the sympathetic innervation to the heart and adrenal demedullation did not alter the decrease in CBF, indicating that the effects of LNAME were not centrally mediated. To determine if the effect of LNAME on CBF was due to a direct action on the coronary vasculature or was secondary to the change in HR, dose-response curves were performed for LNAME (0.3-300 mumol/kg, i.v.) in rats with ventricular pacing. Under these conditions, LNAME still produced an increase in AP and a decrease in CBF, resulting in an increase in coronary vascular resistance. Administration of L-arginine (100-300 mg/kg, i.v.) resulted in a reversal of the cardiovascular effects of LNAME with the reversal being sustained for 1 to 5 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738113 TI - Acetylated endothelin-1 is a constrictor in guinea pig lung vasculature but not in isolated vascular strips. AB - We examined the relative importance of the two amino groups of endothelin-1 in mediating pulmonary vasoconstrictor activity. Complete acetylation of prefolded endothelin-1 (fAcET-1[AcK9]) yielded a product with vasoconstrictor properties (EC50 = 0.52 +/- 0.04 nM) in isolated Ringer-perfused guinea pig lungs similar to native endothelin-1 (EC50 = 0.31 +/- 0.05 nM). However, fAcET-1[AcK9] exhibited a marked reduction in potency when assessed by contraction of isolated guinea pig pulmonary artery strips or by contraction of carotid artery or aortic strip preparations. fAcET-1[AcK9] at concentrations up to 100 nM failed to induce appreciable contraction of any vascular strip preparation. In contrast, endothelin-1 had an EC50 of 1.46 +/- 0.32 to 1.88 +/- 0.19 nM in various vessel preparations. The differences in response to fAcET-1[AcK9] in the intact lung vs. strip preparation suggest different receptor populations in the two preparations. The importance of specific amino groups for contractile activity in the vascular strip preparation was explored by acetylation of individual sites (amino terminus or lysine sidechain) or both sites during peptide synthesis to produce AcET-1, ET 1[AcK9], and AcET-1[AcK9], respectively. The order of potency was endothelin-1 much greater than ET-1[AcK9] greater than AcET-1 greater than AcET-1[AcK9]. These results suggest that chemical modifications (e.g., biotinylation) should be made preferentially at the lysine-9 sidechain in order to retain maximal biological activity in vascular strip preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738114 TI - Regional variation in acute vascular homologous tachyphylaxis. AB - The development of tachyphylaxis or desensitization in a tissue upon repeated application of an agonist is a well-established phenomenon. To investigate the possible basis of vascular homologous tachyphylaxis, vasomotor responses in isolated cerebral and peripheral blood vessels from the cat, dog and rabbit upon repeated application of several agonists were examined using in vitro tissue bath techniques. Tachyphylaxis to vasodilator responses developed to repeated application of vasoactive intestinal polypeptide (VIP) but not to beta adrenergic agonist, forskolin, 8-bromo-cyclic AMP, sodium nitroprusside or 8-bromo-cyclic GMP in feline cerebral arteries. The tachyphylaxis to VIP-induced responses varied among regions and was greatest in the internal carotid artery (ICA), followed by the middle cerebral artery and least in the basilar artery (BA). Cerebral arteries also developed significant tachyphylaxis to constriction induced by repeated applications of neuropeptide Y (NPY), alpha-1 adrenergic agonist, but not to alpha-2 adrenergic agonist, acetylcholine (ACh) or KCl. The tachyphylaxis to constrictions induced by repeated application of neuropeptide Y (NPY) also varied among regions, but was different from that induced by VIP; it was greatest in the BA, followed by the middle cerebral artery and least in the ICA. Similar results were obtained in arteries without endothelial cells. The density of regional innervation of NPY-immunoreactive fibers, which is densest in ICA and sparsest in BA, parallels that of VIP-immunoreactive fibers in these three regions. There is no positive correlation between density of catecholamine fluorescence fibers and degree of tachyphylaxis to noradrenaline-induced constriction in cat ICA, dog saphenous arteries and rabbit ear arteries either.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738115 TI - Conversion of nitroglycerin to nitric oxide in microsomes of the bovine coronary artery smooth muscle is not primarily mediated by glutathione-S-transferases. AB - The pharmacological action of organic nitrate vasodilators [e.g., nitroglycerin (NTG)] is thought to be mediated through metabolic conversion to nitric oxide (NO); conversion leads to vasodilatation, whereas diminished conversion in chronic therapy may lead to pharmacological tolerance. The biochemical nature of this process, however, is poorly understood. Glutathione-S-transferases (GST) have been shown to metabolize organic nitrates in the liver, but it is not known whether these enzymes are involved in this pharmacologically relevant process. We, therefore, compared the activities of conversion of NTG to NO vs. those of GST in microsomal suspensions of bovine coronary artery smooth muscle tissue. A classical GST substrate, 1-chloro-2,4-dinitrobenzene, inhibited NO production in microsomes, suggesting possible involvement of GST in organic nitrate activation. However, GST activity derived from microsomes exhibited a different heat lability profile compared to that of NO generation. Known inhibitors of GST (viz., indomethacin and bromosulfophthalein) did not alter the NO-generating activity in microsomes. Glutathione was a critical cofactor for GST, but not for NO generation from NTG, and thiols other than glutathione (e.g., N-acetyl-L-cysteine and thiosalicylic acid) also could facilitate NO production. Moreover, comparison to a commercially available purified liver GST preparation showed that, at the same GST activity toward 1-chloro-2,4-dinitrobenzene, the microsomal incubation produced about 8 times more NO than the purified liver GST. Radiation inactivation analysis of the functional molecular sizes of GST and the NO producing enzyme(s) suggested that the enzymes were of different molecular weights (54 kD and 160 kD, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738116 TI - Identification of multiple muscarinic binding site subtypes in cat and human cerebral vasculature. AB - The binding characteristics of the nonselective muscarinic antagonist [3H]N methyl scopolamine ([3H]NMS) have been studied in membrane fractions of cat and human cerebral blood vessels. A computer-fitting method was used to analyze the data obtained from association/dissociation, saturation and competition experiments. Specific binding of [3H]NMS to membrane preparations from cat and human pia-arachnoid vessels was found to be saturable (respective Bmax values of 98 +/- 15 and 67 +/- 7 fmol/mg protein) and of high affinity (KD values of 165 +/ 28 and 125 +/- 12 pM, respectively). Competition studies, in the presence of various well-characterized M1, M2 or M3 putative muscarinic antagonists, performed against the binding of [3H]NMS, revealed the heterogeneity of muscarinic binding sites in these vascular tissues. A population of M1 sites was clearly identified in both human and cat pial vessel membranes and accounted for approximately 40 (human) and 20% (cat) of the total population of cerebrovascular muscarinic binding sites labeled with [3H]NMS. Such observation was further supported by saturation studies of [3H]NMS binding performed under M1 blocking conditions (75 nM pirenzepine). Competition and saturation (in the presence of M2 antagonists) studies suggested the presence of M2 sites (approximately 35% of total sites) in cat pial vessels. However, under the same conditions, no M2 binding sites could be detected in human cerebrovascular membranes. A small population of M3 sites (approx. 20%) was found in both human and cat cerebrovascular membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738117 TI - Cardioprotection and attenuation of endothelial dysfunction by organic nitric oxide donors in myocardial ischemia-reperfusion. AB - The effects of two nitric oxide (NO) donors were evaluated in a 6-h model of feline myocardial ischemia-reperfusion. After 80 min of a 90-min ischemic period, SIN-1 or C87-3754 or their respective controls (i.e., 0.9% NaCl or C88-3934, a control compound which does not release NO) were given i.v. as a bolus (0.1 mg/kg) and infused at 1 mg/kg/h for the entire 4.5-h reperfusion period. Administration of the active NO donors significantly decreased the necrotic area/area-at-risk ratio from 29 +/- 3% in the vehicle group to 9 +/- 2 and 11 +/- 5% in the SIN-1 and C87-3754 groups, respectively (P less than .001). The inactive NO donor C88-3934 failed to reduce infarct size (31 +/- 3%). Neither NO donor reduced the accumulation of neutrophils in the necrotic area when compared to their respective control groups, but both agents significantly attenuated coronary endothelial dysfunction as shown by a vasorelaxation to acetylcholine of 62 +/- 2 and 64 +/- 3% in the SIN-1- and C87-3754-treated arteries, as compared to only a 27 +/- 3 and 34 +/- 4% vasorelaxation in the vehicle and inactive NO donor groups, respectively (P less than .001). Our studies show that SIN-1 and C87-3754 exert beneficial effects in a 6-h model of myocardial ischemia reperfusion. Both NO donors decreased myocardial necrosis and decreased the reperfusion-induced endothelial dysfunction without significantly altering the pressure-rate index (i.e., an index of myocardial oxygen demand). PMID- 1738118 TI - Blockade of the ATP-sensitive K+ channel by 5-hydroxydecanoate in guinea pig ventricular myocytes. AB - Effects of a novel antiarrhythmic agent, 5-hydroxydecanoate (5-HD), were investigated on the electrical activity of the guinea pig ventricular myocytes. The shortening of action potential duration induced by applying iodoacetate (IAA) for 5 to 10 min was reversed completely by 5-HD (100 microM) in the papillary muscle. The single channel current recording in the cell-attached configuration revealed both activation of the ATP-sensitive K+ channel during the treatment with IAA and after depression of the channel by the additional application of 100 microM 5-HD. The quick rundown of the ATP-sensitive K+ channel activity interfered the analysis of the drug effect in the usual inside-out patch configuration. The channel activity in the isolated patch was partially recovered and stabilized by applying a tissue extract, which was prepared from guinea pig ventricle. Under this condition relationship between the 5-HD concentration and the K+ channel open probability was characterized with a K1/2 of 0.16 microM and a Hill coefficient of 0.88. The open- and close-time analysis revealed a decrease of the mean duration of the bursting channel opening and an increase of the interburst time under the effect of 5-HD. The inward-rectifier K+ channel, responsible for the resting K+ conductance, was not affected by 5-HD. It was concluded that the curative effect of 5-HD on the shortened action potential in the IAA-treated myocytes is mediated by the depression of the ATP-sensitive K+ channel. PMID- 1738119 TI - Pharmacologic evaluation of A23187-induced contractions of three distinct preparations of guinea pig lung parenchymal strips. AB - The present investigation examined the pharmacologic profiles of three distinct guinea pig lung parenchymal strips (LPS): intact LPS, denuded LPS (devoid of any lung pleura) and pleural surface strips. All three preparations responded similarly to increasing concentrations of KCl, whereas maximum contractile responses of the intact LPS and pleural surface strips to histamine, LTD4 and U46619, a thromboxane A2 mimetic, were significantly greater (P less than 0.001) than those elicited by the denuded LPS. Moreover, concentration-response curves for intact LPS and pleural surface strips to ovalbumin and ionophore A23187 challenges were equivalent to each other, which were significantly (P less than 0.001) higher in magnitude than that for the denuded LPS. The net contractile response of the denuded LPS to A23187 was significantly reduced by 35% in the presence of 1 x 10(-5) M A-64077, a 5-lipoxygenase inhibitor, and nearly abolished with the addition of 1 x 10(-6) M pyrilamine and 4 x 10(-6) M indomethacin. In contrast, the maximum contractile responses of the intact LPS and pleural surface strips were reduced by 40 and 30%, respectively, in the presence of all three inhibitors. On the other hand, morphometric analysis revealed that the density of mast cells in the smooth muscle of lung pleura was as high as that found in the bronchiolar area (2.35 +/- 0.31 vs. 2.62 +/- 0.28 per 0.05 mm2). In contrast, mast cells were scarcely identified in the alveolar parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738120 TI - Affinity of different local anesthetic drugs and catecholamines for the contraluminal transport system for organic cations in proximal tubules of rat kidneys. AB - To study the cellular uptake of [3H]tetraethylammonium (TEA) and its inhibition by different local anesthetic drugs and catecholamines, the capillary stopped flow microperfusion method was used. [3H]TEA concentration in the peritubular capillaries decreased in a time and concentration-dependent manner. This cellular uptake of [3H]TEA could be described by a facilitated diffusion model (Jmax = 0.57 +/- 0.08 pmol sec-1 cm-1, Km = 0.28 +/- 0.01 mmol/l). Between the pKa values of the local anesthetic drugs (range, 2.8-8.9) and their apparent Ki values, a significant correlation was found (r = -0.916, n = 12). In the case of catecholamines, hydrophobic substitution in the form of an alkyl chain in the alpha-position or at the nitrogen increased the inhibitory potency, whereas hydroxyl substitution in the beta-position decreased the affinity. Except for the catecholamines with complex substitutions at the benzene ring (--CH2OH,--NHCONH2, -OOCN[CH3)2, --Cl, --NH2) the apparent Ki values of the catecholamines were directly correlated with the hydrophobicity. It is concluded that hydrophobicity and pKa are two important physicochemical parameters which influence the affinity of a molecule for the transport system for organic cations at the contraluminal side of renal proximal tubules. PMID- 1738121 TI - Beneficial effects of TCV-309, a novel potent and selective platelet activating factor antagonist in endotoxin and anaphylactic shock in rodents. AB - Pharmacological profiles of a novel specific platelet activating factor (PAF) antagonist, TCV-309 (3-bromo-5-[N-phenyl-N-[2-[2- (1,2,3,4-tetrahydro-2 isoquinolycarbonyloxy)ethyl] carbamoyl]ethyl] carbamoyl]-1-propylpyridinium nitrate] and its beneficial effects in shock were examined. TCV-309 specifically inhibited PAF-induced aggregation of rabbit and human platelets, and [3H]PAF binding to rabbit platelet microsomes with IC50 values of 33, 58 and 27 nM, respectively. It was as potent as WEB 2086 and more potent than CV-6209 and CV 3988. TCV-309 did not cause hemolysis in human or rat blood due to a detergent like action. In rats, TCV-309 selectively inhibited the PAF-induced hypotension, hemoconcentration and death with ED50 values of 2.7, 6.4 and 1.7 micrograms/kg (i.v.), respectively. TCV-309 most potently protected mice from death induced by PAF and due to anaphylactic shock with ED50 values of 2.1 and 2.6 micrograms/kg (i.v.), respectively, when compared with CV-3988, CV-6209, WEB 2086 (i.v.) and L 652731 (p.o.). TCV-309 also reversed PAF-induced hypotension and endotoxin induced hypotension in rats with ED50 values of 3.3 and 1.2 micrograms/kg (i.v.), respectively. There was a significant linear relationship between the ability (ED50 value) of these PAF antagonists to prevent death induced by PAF and death due to anaphylactic shock in mice, and between their reversing ability (ED50 value) for the hypotension induced by PAF and endotoxin in rats. TCV-309 (100 micrograms/kg i.v.) protected rats from death induced by endotoxin. Thus, PAF may be a lethal mediator in anaphylactic shock and a hypotensive mediator in endotoxin shock in rodents. PMID- 1738122 TI - Comparative study of the effects of furosemide, ethacrynic acid and bumetanide on the lithium clearance and diluting segment reabsorption in humans. AB - The effect of intravenous administration of the loop diuretics bumetanide, furosemide and ethacrynic acid on lithium (Li) clearance (CLi) and diluting segment reabsorption was studied in seven healthy water-loaded men. According to the increments in minimal urine osmolality (Uosm), ethacrynic acid (which increased Uosm from 59 +/- 4 to 233 +/- 3 mOsmol/kg) had the strongest inhibiting effect on diluting segment reabsorption, whereas that of furosemide and especially bumetanide was significantly less pronounced (rise in Uosm from 56 +/- 3 to 222 +/- 4 and 56 +/- 4 to 192 +/- 2 mOsmol/kg, respectively). In contrast, ethacrynic acid induced a significantly smaller rise in CLi (approximately 14% of the filtered load of Li) than furosemide and bumetanide, which increased Li excretion by approximately 23% and approximately 24% of its filtered load. The observation that the loop diuretic with the most pronounced inhibiting effect in the diluting segment had the smallest effect on CLi makes is unlikely that the increase in CLi induced by loop diuretics is predominantly effected in Henle's loop. PMID- 1738123 TI - A role for phospholipid-derived inflammatory mediators in intestinal anaphylaxis in the rat. AB - This study investigated the role of phospholipid-derived inflammatory mediators in electrolyte transport in the normal rat jejunum and during intestinal anaphylaxis to a food protein in a rat model. In a standard Ussing chamber preparation, the leukotrienes (LTs) C4 and D4 both significantly stimulated an increase in short-circuit current in a concentration-dependent manner. The responses to both LTC4 and LTD4 were significantly reduced by the LTD4 receptor antagonist, MK-571. The 5-lipoxygenase products, LTB4, 5-hydroxyeicosatetraenoic acid and 5-hydroperoxyeicosatetraenoic acid did not significantly alter short circuit current. The thromboxane mimetic, U-46619, had a small, but significant stimulatory effect on short-circuit current. Platelet-activating factor (PAF) caused a significant, concentration-dependent increase in short-circuit current, with effects at concentrations as low as 2 nM and with a maximum effect of 69 +/- 14 microA/cm2. The stimulatory effect of 0.2 microM PAF was significantly reduced by the PAF receptor antagonist WEB 2086. Exposure of sensitized jejunum to ovalbumin caused a biphasic increase in short-circuit current which was reduced by pretreatment with the 5-lipoxygenase inhibitor, L651,392, and the PAF receptor antagonist, WEB 2086. The response to ovalbumin was not significantly affected by pretreatment of the tissue with the LTD4 receptor antagonist, MK-571, at concentrations which inhibited the responses to exogenous LTC4 and LTD4. The thromboxane/endoperoxide receptor antagonist, L670,596, had no significant effect on the short-circuit current response to ovalbumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738124 TI - Effect of yohimbine on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits. AB - The function of presynaptic alpha-2 adrenergic autoinhibition of norepinephrine release was studied in anesthetized rabbits (alfadolone + alfaxalone) with uninterrupted sympathetic impulse traffic. The animals received a tracer infusion of [3H]norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. The results were used to calculate the renal fractional [3H]norepinephrine extraction, the renal removal and spillover of norepinephrine, the total body [3H]norepinephrine clearance and total body norepinephrine spillover. Sodium nitroprusside (10-80 micrograms kg-1 min-1 i.v.), which was infused to modulate sympathetic activity through the baroreceptors, caused hypotension and increased the renal sympathetic firing rate and the renal as well as total body norepinephrine spillover. Increases of total body norepinephrine spillover were much higher than increases of renal spillover. Yohimbine (1 mg kg-1 + 0.2 mg kg-1 hr-1 i.v.) caused slight central sympathoexcitation. In addition, it enhanced the renal and total body spillover of norepinephrine at any given firing rate of the renal sympathetic nerves. The distinguishing feature of this study is the measurement of sympathetic firing rate and norepinephrine spillover in one and the same organ, the kidney. The results demonstrate that the alpha-2 adrenergic autoinhibition of norepinephrine release normally operates in the kidney with intact sympathetic impulse traffic. They also suggest its operation in other peripheral sympathetically innervated tissues. PMID- 1738125 TI - Involvement of nitric oxide in nerve-mediated inhibition and action of vasoactive intestinal peptide in colonic smooth muscle. AB - Neurally mediated relaxation of canine colonic smooth muscle is associated with an increase in the resting membrane potential and is blocked by inhibition of nitric oxide synthesis. N omega-nitro-L-arginine completely prevented nerve mediated relaxation, an effect that was reversed by L-arginine but not D arginine. Vasoactive intestinal peptide (VIP) also relaxed canine colonic smooth muscle. Part of this relaxation was due to activation of inhibitory nerves and this effect was mediated by nitric oxide. In addition to the neurally mediated effect, VIP affected smooth muscle directly. This relaxation was associated with a reduction of the plateau phase of the slow-wave type action potential, without an effect on the resting membrane potential. This action of VIP was similar to that of forskolin which suggests that VIP increases intracellular cyclic AMP. In summary, nitric oxide mediates inhibitory innervation to smooth muscle as well as activation of inhibitory nerves by VIP. The electrophysiological mechanism by which VIP directly affects smooth muscle is described, an effect not mediated by nitric oxide. PMID- 1738126 TI - Biochemical and pharmacological activities of SR 26831, a potent and selective elastase inhibitor. AB - SR 26831 ([[5-(2-chloro-benzyl-2-(terbutyloxycarbonyl)]-4,5,6,7- tetrahydrothieno(3,2-c)pyridine]N-oxide) is the first member of a new class of human leukocyte elastase inhibitors. SR 26831 inhibited in a dose-dependent manner elastases from human leukocytes or pancreas with IC50 values of 80 +/- 2.6 nM and 4.8 +/- 0.12 microM, respectively. Steady-state studies revealed that SR 26831 behaved like a noncompetitive, irreversible inhibitor of both types of enzymes. SR 26831 inhibited in a dose-dependent manner degradation of [3H]elastin and [3H]collagens (types I and IV) by human leukocyte elastase (IC50 values were between 1.2 and 1.8 microM). In this respect, SR 26831 was 3- to 20-fold more active than alpha-1-antitrypsin. SR 26831 was also highly selective for elastases inasmuch as it did not inhibit pepsin, collagenase, trypsin, alpha-chymotrypsin, factor Xa, plasmin, kallikrein, cathepsins B, C, D and G and thrombin. In the rabbit, SR 26831 was cleared rapidly from blood after i.v. injection, but affected intracellular leukocyte elastase activity shortly after either i.v. or p.o. administration. In the rat, i.v. or p.o. administration of SR 26831 prevented in a dose-dependent manner acute lung injury induced by intratracheal instillation of human leukocyte elastase. SR 26831 (1 mg/kg) was still efficient when it was administered 90 min before elastase instillation and was also able to limit further hemorrhage development in response to elastase, after it had begun. SR 26831 may therefore be of therapeutic value in the treatment of diseases such as rheumatoid arthritis or pulmonary emphysema thought to be due to the destructive action of leukocyte elastase. PMID- 1738127 TI - Thromboxane A2 accounts for bronchoconstriction but not for platelet sequestration and microvascular albumin exchanges induced by fMLP in the guinea pig lung. AB - When injected i.v. to guinea pigs, the granulocyte secretagog N-formyl-L methionyl-L-leucyl-L-phenylalanine (fMLP) induces bronchoconstriction (BC), lung platelet sequestration and increased transendothelial albumin exchanges in lungs. We evaluated BC and the variations of the lung contents in radiolabeled platelets, erythrocytes and extravascular albumin, as measurements of platelet lung entrapment, reduction of lung blood volume and increase of transendothelial albumin exchanges, respectively. Trimetoquinol, a thromboxane A2 (TXA2) endoperoxide receptor antagonist, inhibited BC and platelet entrapment by lungs induced by fMLP, but protection was nonspecific because it also suppressed BC by histamine. The specific TXA2 synthetase inhibitor/endoperoxide receptor antagonist ridogrel suppressed BC and reduced lung platelet entrapment, but failed to prevent the increase of extravascular albumin and the decrease of erythrocyte lung contents due to fMLP. Consequently, the fMLP-induced increase of vascular albumin exchanges and reduction of lung blood volume are TXA2 independent. Aspirin prevented BC, but failed to suppress lung platelet entrapment by fMLP, indicating that in vivo platelet activation is not TXA2 dependent, even though the levels of circulating TXB2, the stable metabolite of TXA2, were increased after fMLP concomitantly with that of 6-keto-prostaglandin (PG)F1 alpha, the stable metabolite of PGI2. The ridogrel-treated animals showed reduced blood level of TXB2 and increased levels of 6-keto-PGF1 alpha after fMLP challenge. Blocking the cyclooxygenase pathway with aspirin prevented ridogrel induced protection against lung platelet sequestration after fMLP, supporting the concept that rechanneling of arachidonate metabolism toward protective prostaglandins accounts for protection by ridogrel. PMID- 1738128 TI - Hemoglobin adduct and hepatic- and urinary bladder-DNA adduct levels in rapid and slow acetylator Syrian inbred hamsters administered 2-aminofluorene. AB - The levels of covalently bound arylamine-hemoglobin and DNA adduct formation were used as dosimeters to measure the effect of acetylator genotype and sex on the metabolic conversion of the carcinogen, 2-aminofluorene, to reactive intermediates. A single high dose of 2-aminofluorene (60 mg/kg b.wt. i.p.) was administered to male and female homozygous rapid (Patr/Patr) acetylator hamsters (MHA/SsLaK) and homozygous slow (Pats/Pats) acetylator hamsters (Bio. 82.73/H). By using 32P-postlabeling assay methodology, a sole nonacetylated DNA adduct, which cochromatographed with authentic N-(deoxyguanosin-8-yl)-2-aminofluorene was detected at 3, 6, 12, 18 or 24 hr postdosing in liver and urinary bladder DNA of both rapid and slow acetylator hamsters. The highest levels were detected at 18 hr post 2-aminofluorene injection at which time the average levels of hepatic 2 aminofluorene-DNA adducts were similar between male and female rapid and slow acetylators. By comparison, the levels of 2-aminofluorene-DNA adducts in the urinary bladder at 18 hr were about 4-fold lower than in the liver, and were significantly greater in homozygous rapid than in homozygous slow acetylator counterparts (P less than .01). In both the liver and urinary bladder, the levels of 2-aminofluorene-DNA adducts were independent of sex. In contrast to the DNA adduct data, the levels of 2-aminofluorene-hemoglobin adducts, evaluated by capillary gas chromatography-mass spectrometry, were significantly higher in the homozygous slow acetylators than in homozygous rapid acetylators. However, there again were no differences between males and females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738129 TI - Genetic covariation in low alcohol-sensitive and high alcohol-sensitive selected lines of rats: behavioral and electrophysiological sensitivities to the depressant effects of ethanol and the development of acute neuronal tolerance to ethanol in situ at generation eight. AB - Phenotypic differences in behavioral and initial neuronal sensitivities to acute ethanol (EtOH) administration were examined and compared among replicate lines of rats, which were selectively bred for low and high EtOH sensitivity. The eighth generation of HAS (EtOH-sensitive) and LAS (EtOH-insensitive) rats were significantly different in terms of sensitivity both to EtOH-induced loss of righting response (sleep time) and to EtOH-induced depressions of cerebellar Purkinje neuron firing rates. This study provides the first evidence for a significant correlation between behavioral and electrophysiological EtOH sensitivities among individual animals and between replicate selected rodent lines. These data support the hypothesis that a genetic correlation exists between these two phenotypes. In addition, the LAS rats expressed a significantly higher incidence of acute cellular tolerance to the depressant neuronal effects of repeated local applications of EtOH over a period of a few minutes. We have characterized this response and concluded that it may contribute to EtOH sensitivity. However, our data also suggest that the EtOH insensitivity of cerebellar Purkinje neurons in LAS rats is not only a consequence of acute neuronal tolerance to EtOH, but also due to low initial EtOH sensitivity of these neurons. Both behavioral and electrophysiological EtOH phenotypes of LAS and HAS rats have diverged with the application of selection pressure for behavioral EtOH sensitivity; these data suggest that the mechanisms underlying neuronal sensitivity and acute neuronal tolerance to EtOH are important in determining the behavioral EtOH sensitivities of these animals. PMID- 1738130 TI - Electrophysiological effects of ethanol on hippocampal and cerebellar neurons cografted with locus coeruleus in oculo: role of the noradrenergic circuitry. AB - Nucleus locus coeruleus (LC) was sequentially transplanted with hippocampus or cerebellum from rat fetuses to the anterior eye chamber of adult rat hosts. Histological, electrophysiological and pharmacological studies indicate that the LC neurons survive and functionally innervate neurons in hippocampal and cerebellar cografts. Ethanol, when superfused over the double transplants in urethane-anesthetized hosts, caused excitations of hippocampal neuronal activity at doses between 1 and 30 mM, whereas applications above 30 mM depressed the activity of grafted hippocampal neurons. Similar results were observed in cerebellar Purkinje neurons cografted in oculo, except that cerebellar neurons were more sensitive to both the excitatory and the depressant effects of ethanol. The excitations caused by lower ethanol doses in double grafts were prevented by the cosuperfusion of 0.5 to 1.0 microM clonidine, a treatment which effectively removed the inhibitory influence of the LC neurons from the grafted neuronal circuit by depressing the LC neuronal activity. Ethanol-induced excitations were also not observed in single grafts of hippocampus, which lack a catecholamine innervation. Furthermore, in double grafts, when the noradrenergic inhibition was blocked postsynaptically with the alpha adrenergic antagonist phentolamine, ethanol-induced excitations were prevented, although ethanol did not alter the postsynaptic actions of norepinephrine. Our data suggest that the ethanol-induced excitations in the cerebellar and hippocampal grafts appear to be disinhibitions mediated by an ethanol-induced depression of the inhibitory noradrenergic input to these target tissues from LC cografts. Indeed, the doses of ethanol that induced neuronal excitations in hippocampal transplants also elicited marked depressions of LC neurons. PMID- 1738131 TI - Brief transient ischemia induces long-term depletion of norepinephrine without affecting the aromatic amino acid decarboxylase and monoamine oxidase activities in the rat kidney. AB - Renal artery occlusion (RAO) for 30, 60 or 90 sec was found to reduce norepinephrine tissue levels in both the cortex and medulla of the rat, respectively, by 2 to 5%, 56 to 65% and 92 to 97%, but no significant change in dopamine tissue levels was found to occur. Similar effects were obtained with occlusion of the aorta proximally to the renal arteries for 90 sec. Administration of superoxide dismutase (40 mg/kg) immediately before RAO resulted in a marked protection of the norepinephrine depletion effect as caused by transient ischemia. The sodium-dependent formation of dopamine and 3,4 dihydroxyphenylacetic acid, the deaminated metabolite of dopamine, in renal slices loaded with L-3,4-dihydroxyphenylalanine (50 microM) was found to be similar in denervated and control kidneys. Type A and B monoamine oxidase activities were measured with the deamination of two specific substrates, respectively, [3H]-5-hydroxytryptamine and [14C]-beta-phenylethylamine, in homogenates of the renal cortex and renal medulla; neither type of monoamine oxidase, A or B, was found to be affected by denervation. The renal tissues collected for morphological observation were those in which RAO was performed for 90 sec. The general structure of the renal cortex was not affected by RAO, being similar in the control and the denervated kidney. In conclusion, the results presented suggest that the tissue damaging effect produced by RAO appears to be selective for the renal sympathetic innervation and seems to involve the generation of some reactive oxygen species, namely superoxide. PMID- 1738132 TI - That was then: elderly survivors of incest. AB - 1. Psychosocial ramifications of incest last a lifetime for some and may be of crucial importance in treating patients in the later developmental stages of life. 2. Nursing assessments that include current and past history of violence are important for understanding presenting symptomology and interpersonal dynamics, but they are often neglected. 3. There is a need for nursing research that looks at all facets of elderly incest survivors, including incidence, late life symptomology, and special treatment needs. PMID- 1738133 TI - Preventing spiritual distress in the dying client. AB - 1. Nurses want to provide holistic care to all clients. Viewing spiritual development as a part of human growth and development is appropriate and essential to nursing practice. 2. Nursing care that is effective in maintaining the spiritual integrity of clients nearing death can be effective if placed within a theoretical framework. 3. Levels of spiritual development coupled with the transitional phases of the dying process lead to accurate assessments of clients. In turn, nursing strategies that are selected as a result of such theoretically based assessments are likely to be effective in preventing spiritual distress. PMID- 1738134 TI - Inpatient practice. An integrated framework. AB - A framework for practice that integrates nursing concepts and processes with system concepts has distinct advantages. Nursing concepts provide direction for nursing care; the nursing process provides the structure in which nursing care is delivered and evaluated. Application of system concepts enables the CNS to navigate and negotiate the larger institutional context. Inpatient practice is not just the delivery of quality patient care; it also involves managing the system so it is possible to deliver care. An integrated framework has been offered as a guide to inpatient practice. Although further use and testing are indicated, so far it has proved useful in the practice of a CNS. PMID- 1738135 TI - How will the trend toward biological psychiatry affect the future role of the psychiatric mental health nurse? PMID- 1738136 TI - Comments on public sector nursing. PMID- 1738137 TI - Psychiatric nursing in the 1990s & beyond. AB - In the decade of the '90s, psychiatric mental health nursing will need to take stock of itself--its practice, its education, and its research--if it is to successfully prepare for the changes in care of the mentally ill. Like psychiatrists, we will need to rethink our agendas in light of new science and technology and rationalize the mental health delivery system and our role in it through systematic research and advocate for a system that provides quality care for the chronically ill and the poor. In the next century, we will need to rethink the basics of nursing care and the leadership roles of nurses as hospitals and the doctor's role within them changes. Psychiatric mental health nurses will need to be at the forefront in advocating for a delivery system that listens to patients and families, that humanizes the dehumanizing experience of hospitalization. The challenges before us are formidable. PMID- 1738139 TI - Structure and DNA binding activity of analogues of 1,5-bis(4 amidinophenoxy)pentane (pentamidine) AB - The DNA binding properties of a series of 39 bisbenzamidines related to the clinically used antipneumocystis drug pentamidine (1) were studied. Changes in the thermal denaturation temperature of calf thymus DNA (delta Tm) showed that all the compounds have significant affinity for DNA. A comparison of delta Tms for the series with delta Tms of base-pair-specific DNA-binding compounds, using homopolymers poly(dA).poly(dT) and poly(dG-dC).poly(dG-dC), indicated that the compounds show moderate specificity for AT base pairs. Lack of DNA helix extension, measured by viscometric titration with sonicated calf thymus DNA, indicated that the compounds do not bind to DNA by intercalation. Analogues of 1 with an odd number of methylenes connecting the benzamidine rings had a higher affinity for DNA and homopolymers than analogues with an even number of methylenes. All of the compounds containing an amidino group meta to the linking chain showed lower polynucleotide affinity. These results suggest that the shape of the molecules was important for DNA binding. Molecular modeling studies showed a correlation between the DNA binding and the radius of curvature of molecular mechanics models of the molecules. Monosubstitution on the benzamidine rings or replacement of the amidino group with the cyclic imidazolino group had no influence on the DNA-binding affinity of the compounds. Substitution of NH for the ether oxygen connecting group of 1 had no effect on the DNA binding or base pair specificity. Methylation of either of the nitrogen atoms of the imidazolino group to provide an analogue of 1 with N-methylimidazolino groups decreased DNA affinity considerably. GC vs AT base-pair specificity as measured by delta Tm does not correlate with the radius of curvature. The experimental and modeling results are consistent with DNA minor-groove binding. PMID- 1738140 TI - alpha-Keto amide inhibitors of aminopeptidases. AB - The design and synthesis of 3-amino-2-oxo-4-phenylbutanoic acid amides (alpha keto amides), a new class of aminopeptidase inhibitor, are described. These compounds, illustrated by the Phe-Leu analogue 2, are effective inhibitors of arginyl aminopeptidase (Ki = 1.5 microM), cytosol aminopeptidase (Ki = 1.0 microM), and microsomal aminopeptidase (Ki = 2.5 microM). The ketone carbonyl of the alpha-keto amide was found to hydrate readily in an aqueous DMSO solution, due to the electron-withdrawing effect of the neighboring amide group. A mechanism of inhibition is proposed for the alpha-keto amides that is similar to that proposed for the structurally related aminopeptidase inhibitor bestatin and its analogues, wherein the inhibitor may interact with the S1'-S2' subsite of the enzyme rather than the S1-S1' subsite. Like bestatin, the alpha-keto amides are slow-binding inhibitors of all three enzymes. PMID- 1738138 TI - Adenosine receptors: pharmacology, structure-activity relationships, and therapeutic potential. PMID- 1738141 TI - Potent, orally active aldose reductase inhibitors related to zopolrestat: surrogates for benzothiazole side chain. AB - A broad structure-activity program was undertaken in search of effective surrogates for the key benzothiazole side chain of the potent aldose reductase inhibitor, zopolrestat (1). A structure-driven approach was pursued, which spanned exploration of three areas: (1) 5/6 fused heterocycles such as benzoxazole, benzothiophene, benzofuran, and imidazopyridine; (2) 5-membered heterocycles, including oxadiazole, oxazole, thiazole, and thiadiazole, with pendant aryl groups, and (3) thioanilide as a formal equivalent of benzothiazole. Several benzoxazole- and 1,2,4-oxadiazole-derived analogues were found to be potent inhibitors of aldose reductase from human placenta and were orally active in preventing sorbitol accumulation in rat sciatic nerve, in an acute test of diabetic complications. 3,4-Dihydro-4-oxo-3-[(5,7-difluoro-2-benzoxazolyl)methyl] 1- phthalazineacetic acid (124) was the best of the benzoxazole series (IC50 = 3.2 x 10(-9) M); it suppressed accumulation of sorbitol in rat sciatic nerve by 78% at an oral dose of 10 mg/kg. Compound 139, 3,4-dihydro-4-oxo-3-[[(2 fluorophenyl)-1,2,4- oxadiazol-5-yl]methyl]-1-phthalazineacetic acid, with IC50 less than 1.0 x 10(-8) M, caused a 69% reduction in sorbitol accumulation in rat sciatic nerve at an oral dose of 25 mg/kg. The thioanilide side chain featured in 3-[2-[[3-(trifluoromethyl)phenyl]amino]-2-thioxoethyl]-3,4-dihydro - 4-oxo-1 phthalazineacetic acid (195) proved to be an effective surrogate for benzothiazole. Compound 195 was highly potent in vitro (IC50 = 5.2 x 10(-8) M) but did not show oral activity when tested at 100 mg/kg. Additional structure activity relationships encompassing a variety of heterocyclic side chains are discussed. PMID- 1738142 TI - 3-Carboxy-5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide, a new prodrug for the antiarthritic agent 2-cyano-3-hydroxy-N-[4 (trifluoromethyl)phenyl]-2-butenamide. AB - The title compound 3-carboxyisoxazole 3 was synthesized by cycloaddition of carbethoxyformonitrile oxide to N-[4-(trifluoromethyl)phenyl]-3-pyrrolidino-2 butenamide (6) with spontaneous elimination of pyrrolidine followed by hydrolysis of the ethyl ester. Compound 3 was shown to be absorbed intact after oral administration to rats. Over 24 h, the compound was metabolized to yield plasma concentrations of the antiinflammatory agent 2-cyano-3-hydroxy-N-[4 (trifluoromethyl)phenyl]-2-butenamide (2), similar to those obtained following an equivalent dose of the established prodrug of 5-methyl-N-[4 (trifluoromethyl)phenyl]isoxazole-4-carboxamide (1). PMID- 1738143 TI - Synthesis and cytotoxic activity of C-glycosidic nicotinamide riboside analogues. AB - The C-glycosidic nicotinamide riboside analogue (2) was prepared by reaction of ribonolactone 24 with the lithiated oxazoline 19 followed by triethylsilane reduction to 26 and deprotection. Selective phosphorylation to the pseudonucleotide 34 was effected via the isopropylidene compound 33. In contrast to the benzoic acid riboside (28) the benzamide riboside (2) showed extremely high cytotoxicity at nanomolar concentrations to S49.1 lymphoma cells but only slightly increased dexamethasone toxicity. PMID- 1738144 TI - Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8 naphthyridine-3-carboxylic acids. AB - A series of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids have been prepared and tested for their in vitro and in vivo antibacterial activities. The 5-methyl group gave better in vitro activity with the 1-cyclopropyl appendage, but poorer activity with the 1-tert butyl moiety. With the 1-(2,4-difluorophenyl) substitution, the influence of the 7-cycloalkylamino group was determinant: a (3S)-3-amino-pyrrolidine was shown to enhance greatly the in vitro and in vivo activity of the 5-methyl derivative. Compound 33 (BMY 43748) was selected as a promising candidate for an improved therapeutic agent. PMID- 1738145 TI - Synthesis and anti-HIV activity of 4'-thio-2',3'-dideoxynucleosides. AB - A series of 2',3'-dideoxy-4'-thionucleoside analogues of purines and pyrimidines, including 4'-thioddI (17), 4'-thioddC (27), and 4'-thioAZT (34), were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV). A stereospecific synthesis of the 2,3-dideoxy-4-thioribofuranosyl carbohydrate precursor 11 starting with L-glutamic acid is described. 2',3' Dideoxy-4'-thiocytidine (27) displayed significant, but modest activity in vitro against human immunodeficiency virus. PMID- 1738146 TI - Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents. AB - A series of methyl and ethyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates (7 19) and methyl 5-carbamoyl-1H-benzimidazole-2-carbamates (24-34) have been synthesized via the reaction of an appropriate alcohol or amine with the acid chloride derivatives 6a or 6b at room temperature. Reaction of an alcohol with acid chloride 6a at reflux temperature afforded transesterified products 20-23 in good yield. Treatment of methyl 5-amino-1H-benzimidazole-2-carbamate with substituted benzoyl chlorides furnished the methyl 5-benzamido-1H-benzimidazole-2 carbamates (36-38). Compounds 9, 16, 20, and 22 demonstrated significant growth inhibition in L1210 cells with IC50's less than 1 microM. Growth inhibition by this series of compounds appears to be associated with mitotic spindle poisoning. All the compounds tested, 9, 10, 19, 20, 22, and 23, caused significant accumulation of L1210 cells in mitosis. Compounds 7, 9, 19, 25, 26, 27, and 36 showed significant in vivo antifilarial activity against adult worms of Brugia pahangi, Litomosoides carinii, and Acanthocheilonema viteae in experimentally infected jirds. PMID- 1738147 TI - alpha-Methylated analogues of triiodothyroalkanoic acids: synthesis and biological activity. AB - Three novel thyroid hormone analogues: alpha-methyl-3,5,3'-triiodothyroacetic acid, alpha-methyl-3,5,3'-triiodothyropropionic acid, and alpha-methyl-3,5,3',5' tetraiodothyropropionic acid were synthesized. The hepatic thyroid receptor affinity of these analogues was compared to that other available thyroid analogues. The ability of these compounds to increase the activity of two hepatic enzymes and to lower blood cholesterol was compared to that of L triiodothyronine. alpha-Methyl-3,5,3'-triiodothyroacetic acid was shown to have less nuclear binding affinity, less enzyme inducing ability, but more blood cholesterol lowering ability than triiodothyroacetic acid. alpha-Methyl-3,5,3',5' tetraiodothyropropionic acid showed less nuclear binding affinity and less enzyme inducing activity than alpha-methyl-3,5,3'-triiodothyropropionic acid. PMID- 1738148 TI - Renin inhibitory pentols showing improved enteral bioavailability. AB - Incorporation of a C-terminal pentahydroxy functionality led to potent, low molecular weight hydrophilic renin inhibitors lacking the P1' side chain. As these compounds are easy to synthesize and have sufficient water solubility, they were chosen for further study. Compound 33 was transported across rabbit intestinal brush border membrane vesicles and yielded a hypotensive effect in sodium-depleted rhesus monkeys which lasted for 90 min when dosed at 2 mg/kg id. PMID- 1738149 TI - Base-catalyzed isomerization of retinoic acid. Synthesis and differentiation inducing activities of 14-alkylated all-trans-, 13-cis-, and 20,14-retro-retinoic acids. AB - Retinoic acid (1) is isomerized regioselectively by excess amounts of lithium diisopropylamide (LDA) to give 20,14-retro-retinoic acid (3). Alkylation of the intermediate dianion of retinoic acid gave 14-alkylated derivatives of 3. By isomerization of the alkylated retro isomers under basic conditions, several 14 alkyl-all-trans- and -13-cis-retinoic acids were synthesized. The retinoidal activities of these derivatives were examined, based on the ability to induce differentiation of human promyelocytic leukemia cell line HL-60. 20,14-retro Retinoic acid (3) is 1/50 as active as retinoic acid (1). Although 14-methyl 20,14-retro-retinoic acid (4) is as active as 3, the introduction of a 14-methyl group into all-trans- and 13-cis-retinoic acid resulted in decreased activity. Introduction of bulkier alkyl groups at the C-14 position caused the disappearance of the activity. PMID- 1738150 TI - Multivariate analysis by the minimum spanning tree method of the structural determinants of diphenylethylenes and triphenylacrylonitriles implicated in estrogen receptor binding, protein kinase C activity, and MCF7 cell proliferation. AB - The response profiles of 36 para-substituted diphenylethylenes (DPEs) and triphenylacrylonitriles (TPEs) have been compared by multivariate analysis. The responses measured were (a) relative binding affinity (RBA) for the cytosol estrogen receptor (ER), (b) ability to promote the growth of the human MCF7 breast cancer cell-line, (c) cytotoxicity in MCF7 cells, and (d) ability to stimulate or inhibit protein kinase C (PKC) III activity under three different conditions of enzyme activation. The prime object of the analysis was to observe the simultaneous influence of diverse combinations of substituents on all these in vitro responses. To do this, the minimum spanning tree (MST) method was used to organize the molecules into a network in which proximate molecules are closely related with regard to their responses whereas remote molecules are distinct. The MST of this population of molecules had four main branches. E2 and its TPE mime were located in a central position within the trunk whereas the tips of the branches tended toward molecules of different specificity, i.e., cytotoxic molecules that bind to ER and interfere with PKC, noncytotoxic molecules that also bind to ER and interfere with PKC but promote cell growth, molecules only active on PKC, and molecules active on all parameters except PKC stimulation. A parallel MST analysis of the relationships among the response parameters themselves confirmed previous conclusions: For this population of molecules, RBAs for ER are fairly closely related to ability to promote MCF7 cell growth and only little to cytotoxicity (Bignon et al. J. Med. Chem. 1989, 32, 2092). Cytotoxicity is much more clearly correlated with inhibition of diacylglycerol-stimulated PKC activity than with RBAs for ER. PKC inhibition differs substantially depending upon whether the substrate is H1 histone or protamine sulfate. PMID- 1738151 TI - QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. AB - QSAR analyses have been performed on the substituted indanone and benzylpiperidine ring substructures of a set of acetylcholinesterase, AChE, inhibitors of which 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride is a potent in vitro and ex vivo inhibitor. The method of molecular decomposition-recomposition was used to define the sets of molecular substructures and corresponding in vitro inhibition databases. A QSAR involving the magnitude of the dipole moment, the highest occupied molecular orbital (HOMO) energy, and a specific pi-orbital wave function coefficient of the substituted indanone ring substructure was constructed and found to be significant. The absence of any molecular-shape or bulk term in the QSAR, coupled with some of the relatively large substituents used to construct the QSAR, suggests considerable space is available around the indanone ring during the inhibition process. A set of QSARs were constructed and evaluated for substituents on the aromatic ring of the benzylpiperidine substructure. The most significant QSAR involves a representation of molecular shape, the largest principal moment of inertia, and the HOMO of the substituted aromatic ring. It appears that upon binding the receptor "wall" is closely fit around the benzyl ring, especially near the para position. Overall, the QSAR analysis suggests inhibition potency can be better enhanced by substitution on the indanone ring, as compared to the aromatic sites of the benzylpiperidine ring. Moreover, inhibition potency can be rapidly diminished, presumably through steric interactions with the receptor surface of AChE, by substitution of moderate to large groups on the benzyl ring, particularly at the para position. PMID- 1738152 TI - Conformational analyses and molecular-shape comparisons of a series of indanone benzylpiperidine inhibitors of acetylcholinesterase. AB - Conformational analyses and molecular-shape comparisons were carried out on an analogue series of indanone-benzylpiperidine inhibitors of acetylcholinesterase (AChE). It was possible to define an active conformation with respect to the flexible geometry of the benzylpiperidine moiety, as well as an active conformation of the indanone ring-piperidine ring substructure for analogues having a single spacer group between these rings. No active conformation could be postulated for analogues having two or three spacer units between the indanone and piperidine conformation could be postulated for analogues having two or three spacer units between the indanone and piperidine rings. Still, a receptor binding model can be constructed for all indanone and piperidine ring substructures. The postulated active conformation for 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2 yl)methyl]piperidine hydrochloride (1a), a potent AChE inhibitor, is close to the crystal structures of 1a with respect to the indanone-piperidine substructure, but differs from the crystal structures for the benzylpiperidine moiety. However, the crystal conformations and the postulated active conformation of the benzylpiperidine portion of the AChE inhibitor are estimated to be about equally stable. A trans-decalin analogue of 1a can adopt the postulated active conformation as shown by calculation and as seen in its crystal structure. The inactivity of this analogue is explained by the added steric size of the decalin unit and/or the time-average valence geometry behavior at the spiro junction to the indanone ring. PMID- 1738153 TI - A novel class of enkephalinase inhibitors containing a C-terminal sulfo group. AB - A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3 mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test. PMID- 1738154 TI - Electron microscopy of the actin-myosin head complex in the presence of ATP. AB - The structure of the actin-myosin head complex during the ATPase cycle has been studied by electron microscopy of negatively stained acto-heavy-meromyosin. In the absence of ATP, heavy meromyosin molecules generally showed a regular, angled appearance, with both heads attached to the actin filament. In the presence of ATP, attached molecules showed a less ordered structure, often with only one head attached. We conclude that configurations other than the rigor structure occur during the actomyosin cross-bridge cycle. PMID- 1738155 TI - Genetic and functional analysis of the basic replicon of pPS10, a plasmid specific for Pseudomonas isolated from Pseudomonas syringae patovar savastanoi. AB - The sequence of a 1823 base-pair region containing the replication functions of pPS10, a narrow host-range plasmid isolated from a strain of Pseudomonas savastanoi, is reported. The origin of replication, oriV, or pPS10 is contained in a 535 base-pair fragment of this sequence that can replicate in the presence of trans-acting function(s) of the plasmid. oriV contains four iterons of 22 base pairs that are preceded by G+C-rich and A+T-rich regions. A dnaA box located adjacent to the repeats of the origin is dispensable but required for efficient replication of pPS10; A and T are equivalent bases at the 5' end of the box. repA, the gene of a trans-acting replication protein of 26,700 Mr has been identified by genetic and functional analysis. repA is adjacent to the origin of replication and is preceded by the consensus sequences of a typical sigma 70 promoter of Escherichia coli. The RepA protein has been identified, using the minicell system of E. coli, as a polypeptide with an apparent molecular mass of 26,000. A minimal pPS10 replicon has been defined to a continuous 1267 base-pair region of pPS10 that includes the oriV and repA sequences. PMID- 1738156 TI - Crystal structure of the alkaline proteinase Savinase from Bacillus lentus at 1.4 A resolution. AB - Savinase (EC3.4.21.14) is secreted by the alkalophilic bacterium Bacillus lentus and is a representative of that subgroup of subtilisin enzymes with maximum stability in the pH range 7 to 10 and high activity in the range 8 to 12. It is therefore of major industrial importance for use in detergents. The crystal structure of the native form of Savinase has been refined using X-ray diffraction data to 1.4 A resolution. The starting model was that of subtilisin Carlsberg. A comparison to the structures of the closely related subtilisins Carlsberg and BPN' and to the more distant thermitase and proteinase K is presented. The structure of Savinase is very similar to those of homologous Bacillus subtilisins. There are two calcium ions in the structure, equivalent to the strong and the weak calcium-binding sites in subtilisin Carlsberg and subtilisin BPN', well known for their stabilizing effect on the subtilisins. The structure of Savinase shows novel features that can be related to its stability and activity. The relatively high number of salt bridges in Savinase is likely to contribute to its high thermal stability. The non-conservative substitutions and deletions in the hydrophobic binding pocket S1 result in the most significant structural differences from the other subtilisins. The different composition of the S1 binding loop as well as the more hydrophobic character of the substrate binding region probably contribute to the alkaline activity profile of the enzyme. The model of Savinase contains 1880 protein atoms, 159 water molecules and two calcium ions. The crystallographic R-factor [formula; see text]. PMID- 1738157 TI - Crystallization and preliminary X-ray analysis of complexes of peptide inhibitors with human recombinant and mouse submandibular renins. AB - Inhibitor-complexed crystals of mouse and human renins suitable for X-ray analysis have been prepared. The mouse renin is complexed with a non-hydrolysable decapeptide analogue of rat angiotensinogen containing a hydroxyethylene isostere in place of the scissile bond. The crystals are monoclinic, space group P2(1) with cell dimensions a = 78.3 A, b = 117.8 A, c = 85.9 A, beta = 101.18 degrees containing four molecules per asymmetric unit. The human renin is fully glycosylated and complexed with a tetrapeptide containing norstatine. The complex crystallises in the cubic space group P2(1)3 with a = 143.1 A and has two molecules in the asymmetric unit. The rotation function of the mouse renin complex indicates pseudo 222 symmetry while that of human renin indicates a pseudo 2-fold axis. Full structural analyses of the two complexes are underway. PMID- 1738158 TI - Investigations on the dynamic structures of adenine- and thymine-containing DNA. AB - The structures of poly(dA-dT), poly(dA-dBr5U) and of poly(dA).poly(dT) have been investigated in solution and in fibers, by Raman spectroscopy. Both the alternating poly(dA-dT), poly(dA-dBr5U) and non-alternating poly(dA).poly(dT) exhibit, in the region of sugar phosphate backbone vibrations, two bands of almost equal intensity at about 841 cm-1 and 817 cm-1. The analysis of the characteristic bands of thymine residues that are sensitive to sugar puckers gives indication of a significant displacement from the C(2')-endo conformer suggesting the adoption of alternative conformers such as O(4')-endo. In contrast, the diagnostic Raman bands for the sugar pucker of adenine residues suggest, instead, predominant adoption of C(2')-endo conformations. These Raman results are compatible with rapid dynamic changes of sugar puckers between C(2') endo and O(4')-endo for the thymidine (and uridine) residues, whereas in adenine residues the sugar puckers fluctuate around the C(2')-endo pucker in all synthetic DNA molecules studied. Molecular dynamics simulations, performed on six different starting models using two distance-dependent dielectric functions epsilon(r) = 4 r and a sigmoidal dependence), all gave similar dynamic behavior in agreement with these Raman data and their interpretation. The mean calculated pseudorotation phases of the adenine residues are systematically higher (around C(2')-endo) than those of the thymine residues (close to O(4')-endo-C(1')-exo). Besides, the mean lifetimes of the thymine residues are 1.5 to 2.0-fold higher in the O(4')-endo than in the C(2')-endo domain, while those of the adenine residues are two to threefold higher in the C(2')-endo than in the O(4')-endo domain. In the Raman spectra of the alternating poly(dA-dBr5U), the splitting of a band into two components arising from the two contributions of ApBr5U and Br5UpA provides strong evidence for a repeating dinucleotide structure in solution. The calculated twist values averaged over the simulation runs are also systematically higher in the 5'T-A3' step (39 degrees) than in the 5'A-T3' step (33 degrees). Simultaneously, the calculated roll values are positive in the 5'T-A3' step (6 degrees) and negative in the 5'A-T3' step (-9 degrees), while the propeller twist values are about the same (-11 degrees to -16 degrees). On the other hand, in the homopolymer, the average twist value is close to 36 degrees with the roll angle close to 0 degrees and large propeller twist values (-20 degrees). PMID- 1738160 TI - Energy-optimized structure of antifreeze protein and its binding mechanism. AB - A combination of Monte Carlo simulated annealing and energy minimization was utilized to determine the conformation of the antifreeze protein from the fish winter flounder. It was found from the energy-optimized structure that the hydroxyl groups of its four threonine residues, i.e. Thr2, Thr13, Thr24, Thr35, are aligned on almost the same line parallel to the helix axis and separated successively by 16.1, 16.0 and 16.2 A, respectively, very close to the 16.6 A repeat spacing along [0112] in ice. Based on such a space match, a zipper-like model is proposed to elucidate the binding mechanism of the antifreeze protein to ice crystals. According to the current model, the antifreeze protein may bind to an ice nucleation structure in a zipper-like fashion through hydrogen bonding of the hydroxyl groups of these four Thr residues to the oxygen atoms along the [0112] direction in ice lattice, subsequently stopping or retarding the growth of ice pyramidal planes so as to depress the freeze point. The calculated results and the binding mechanism thus derived accord with recent experimental observations. The mechanistic implications derived from such a special antifreeze molecule might be generally applied to elucidate the structure-function relationship of other antifreeze proteins with the following two common features: (1) recurrence of a Thr residue (or any other polar amino acid residue whose side chain can form a hydrogen bond with water) in an 11-amino-acid period along the sequence concerned; and (2) a high percentage of Ala residue component therein. Further experiments are suggested to test the ice binding model. PMID- 1738159 TI - Three-dimensional structure of the bifunctional enzyme phosphoribosylanthranilate isomerase: indoleglycerolphosphate synthase from Escherichia coli refined at 2.0 A resolution. AB - The three-dimensional structure of the monomeric bifunctional enzyme N-(5' phosphoribosyl)anthranilate isomerase:indole-3-glycerol-phosphate synthase from Escherichia coli has been refined at 2.0 A resolution, using oscillation film data obtained from synchrotron radiation. The model includes the complete protein (452 residues), two phosphate ions and 628 water molecules. The final R-factor is 17.3% for all observed data between 15 and 2 A resolution. The root-mean-square deviations from ideal bond lengths and bond angles are 0.010 A and 3.2 degrees, respectively. The structure of N-(5'-phosphoribosyl)anthranilate isomerase: indole-3-glycerol-phosphate synthase from E. coli comprises two beta/alpha-barrel domains that superimpose with a root-mean-square deviation of 2.03 A for 138 C alpha-pairs. The C-terminal domain (residues 256 to 452) catalyses the PRAI reaction and the N-terminal domain (residues 1 to 255) catalyses the IGPS reaction, two sequential steps in tryptophan biosynthesis. The enzyme has the overall shape of a dumb-bell, resulting in a surface area that is considerably larger than normally observed for monomeric proteins of this size. The active sites of the PRAI and the IGPS domains, both located at the C-terminal side of the central beta-barrel, contain equivalent binding sites for the phosphate moieties of the substrates N-(5'-phosphoribosyl) anthranilate and 1-(o carboxyphenylamino)-1-deoxyribulose-5-phosphate. These two phosphate binding sites are identical with respect to their positions within the tertiary structure of the beta/alpha-barrel, the conformation of the residues involved in phosphate binding and the hydrogen-bonding network between the phosphate ions and the protein. The active site cavities of both domains contain similar hydrophobic pockets that presumably bind the anthranilic acid moieties of the substrates. These similarities of the tertiary structures and the active sites of the two domains provide evidence that N-(5'-phosphoribosyl)anthranilate isomerase:indole 3-glycerol-phosphate synthase from E. coli results from a gene duplication event of a monomeric beta/alpha-barrel ancestor. PMID- 1738161 TI - Molecular dynamics simulation of the DNA triplex d(TC)5.d(GA)5.d(C+T)5. AB - A molecular dynamics simulation of the DNA triple helix d(TC)5.d(GA)5.d(C+T)5 is described (C+ represents a protonated cytosine residue). The simulation has been performed using the program AMBER 3.1 and includes counterions and explicit solvent under periodic boundary conditions. Both the dynamic and time-averaged behaviour of the system has been analysed. Considerable deviations from the fibre diffraction model for DNA triple helix structure are observed, including the repuckering of the purine strand sugars that has been identified in some nuclear magnetic resonance (n.m.r.) studies. The simulation suggests that this conformational change may be driven by the possibility of improved interactions between the phosphate groups of this strand and both the solvent and counterions. Several examples of a particular conformational transition are observed, involving correlated changes in the backbone angles alpha and gamma. These transitions provide a possible explanation for some unusual n.m.r. data that have been reported. The structure of the triple helix major groove also suggests an explanation for the observed stabilization of DNA triplexes by polyvalent cations, and their ability to interact with drugs that bind in the minor groove of DNA duplexes. PMID- 1738162 TI - beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors. AB - Previous crystallographic analyses of the Kunitz inhibitors from soybean. Erythrina caffra and wheat, the interleukins-1 beta and 1 alpha and the acidic and basic fibroblast growth factors have shown that they contain a most unusual fold. It is formed by six two-stranded hairpins. Three of these form a barrel structure and the other three are in a triangular array that caps the barrel. The arrangement of the secondary structures gives the molecules a pseudo 3-fold axis. Although the different proteins have very similar structures, many of their sequences have no significant similarities overall. The structural determinants of this fold are described and discussed in this paper. The barrels in the different proteins have the same geometrical features: six strands tilted at 56 degrees to the barrel axis; a barrel diameter of 16 A, and the beta-sheet hydrogen bonded so that it is staggered with a shear number of 12. These features fit McLachlan's equations for ideal barrels formed by beta-sheets. The wide diameter of the barrels is filled by layers of residues that, while not identical in the different proteins, are, in almost all cases, large. The structure of the triangular array of hairpins is determined by the coiling of the strands and the packing of hairpin residues against each other and against residues from the interior of the barrel. The major sequence requirements of this fold are large or medium hydrophobic residues at 18 buried sites. In the different structures the total volume of these residues is 3000 (+/- 120) A. The polyhedron model of protein architecture is used to demonstrate that the main, and in particular the symmetrical, features of this fold arise from the ideal and equal packing of six hairpins, modified only slightly to form hydrogen bonds between the hairpins. PMID- 1738163 TI - Dissociation of a native dimer to a molten globule monomer. Effects of pressure and dilution on the association equilibrium of arc repressor. AB - The monomer-dimer association reaction of Arc repressor was studied by pressure induced dissociation and by dilution. The dissociation was measured by the decrease (red shift) in the average energy of emission of the tryptophan fluorescence. Pressure dissociation also promoted a decrease in the excited-state lifetime of the single tryptophanyl residue, Trp14. These observations suggest that Trp14 becomes exposed to an aqueous environment following dissociation. The pressure-dissociation curves were concentration dependent, with p1/2 (half dissociation pressure) shifting to higher pressures as the concentration increased. The dissociation constant (KdO) obtained by extrapolating the pressure dissociation curves to atmospheric pressure was similar to that determined from the dilution curve (KdO = 30 nM). An anomalous steepness of dissociation in response to dilution was observed, suggesting that conformational changes occur as a result of dissociation of Arc repressor. Binding of bis(8-anilinonaphthalene 1-sulfonate) to Arc repressor was not significantly affected by pressure dissociation, whereas thermal or urea denaturation was accompanied by a dramatic decrease in binding. These results suggest that the conformational changes that follow dissociation induced by pressure are more limited than those following denaturation. The tryptophan anisotropy decreased by about one-half, suggesting the dissociation of a globular dimer to a compact monomer. On the other hand, denaturation by urea promoted an increase in anisotropy, as expected for a random coil conformation. Dissociated Arc has the hydrodynamic properties of a folded monomer. On the other hand, dissociated Arc has a high degree of exposure of hydrophobic side-chains, and the distribution of conformations is much broader than that in the folded dimer. These features suggest that the dissociated subunit is a molten globule. The subunit interaction was substantially increased by a single amino acid substitution (Pro8----Leu), and the free energy of stabilization amounted to -2.9 kcal/mol. This increased stability suggests that residue 8 is located in the dimer interface and that part of the tertiary and most of the quaternary structure constraints result from the interaction between the intersubunit beta-strands. PMID- 1738164 TI - Crystal structure of the complex between carboxypeptidase A and the biproduct analog inhibitor L-benzylsuccinate at 2.0 A resolution. AB - The X-ray crystal structure of the carboxypeptidase A-L-benzylsuccinate complex has been refined at 2.0 A resolution to a final R-factor of 0.166. One molecule of the inhibitor binds to the enzyme active site. The terminal carboxylate forms a salt link with the guanidinium group of Arg145 and hydrogen bonds with Tyr248 and Asn144. The second carboxylate group binds to the zinc ion in an asymmetric bidentate fashion replacing the water molecule of the native structure. The zinc ion moves 0.5 A from its position in the native structure to accommodate the inhibitor binding. The overall stereochemistry around the zinc can be considered a distorted tetrahedron, although six atoms of the co-ordinated groups lie within 3.0 A from the zinc ion. The key for the strong inhibitory properties of L benzylsuccinate can be found in its ability both to co-ordinate the zinc and to form a short carboxyl-carboxylate-type hydrogen bond (2.5 A) with Glu270. PMID- 1738166 TI - Breast cancer and taxol top press and public interest: "the" cancer stories of 1991. PMID- 1738165 TI - Two crystal forms of the lentil lectin diffract to high resolution. AB - The legume lectins are an important class of polysaccharide-binding proteins with a wide range of biochemical and immunological applications. Two high-resolution crystal forms are obtained for the lentil (Lens culinaris) lectin: a monoclinic P21 and an orthorhombic P212121. The unit cell dimensions for the monoclinic form are a = 58.0 A, b = 56.0 A, c = 82.1 A, beta = 104.4 degrees, while for the orthorhombic form a = 56.4 A, b = 74.6 A, c = 124.9 A. The asymmetric unit contains one dimer in both cases. The crystals diffract to 1.7 A resolution using synchrotron radiation. Preliminary data have been collected to 2.3 A on both crystal forms using a conventional X-ray source. PMID- 1738167 TI - Prevention centers planned for U.S., France. PMID- 1738168 TI - Drug development link between U.S. and Europe yielding results. PMID- 1738169 TI - Breast cancer surveillance: on increasing its effectiveness while reducing its negative psychological effects. PMID- 1738170 TI - Psychological distress and surveillance behaviors of women with a family history of breast cancer. AB - Women with a family history of breast cancer are at increased risk for developing the disease. This study investigated the beliefs of women at high risk for breast cancer (one or more first-degree relatives with breast cancer) about their breast cancer risk and the impact of this information on their surveillance behaviors and psychological distress. The Health Belief Model and the Fear Arousing Communications Theory were used in this study. Two hundred and seventeen women, enrolled in a breast protection program, completed a questionnaire regarding health beliefs and behaviors, social support, and psychological distress. While 94% came in for regularly scheduled mammograms, only 69% came in for regular clinical breast examinations. A discriminant function analysis revealed that increased cancer anxiety decreased regular clinical examinations (coefficient = .65). Only 40% performed breast self-examination monthly, 10% never performed breast self-examination, and 50% did not perform breast self-examination regularly. High breast self-examination performance prior to coming to the program was the best predictor of current breast self-examination, and high anxiety predicted poor adherence to monthly breast self-examination (multiple R = .61). More than 27% of the women at high risk were defined as having a level of psychological distress consistent with the need for counseling. Women reporting more barriers to screening, fewer social supports, and low social desirability had more psychological distress (multiple R = .75). Higher anxiety was directly related to poor attendance at a clinical breast examination and poor adherence to monthly breast self-examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738171 TI - Suramin, an active nonhormonal cytotoxic drug for treatment of prostate cancer: compelling reasons for testing in patients with hormone-refractory breast cancer. PMID- 1738172 TI - Inhibition of breast cancer growth by suramin. AB - In this study, the polyanionic compound suramin was shown to be a potent in vitro growth inhibitor of both hormone-insensitive, estrogen receptor-negative human breast cancer cells (MDA MB231 and SK-BR-3) and hormone-responsive, estrogen receptor-positive human breast cancer cells (ZR 75-1, T47D, and MCF7). The inhibitory effect of suramin was dose dependent, with a median effective dose varying from 7 microM for MDA MB231 cells to 50 microM for MCF7 cells. This result indicated that estrogen receptor-negative cells were more sensitive to the drug. In MCF7 cells, not only did suramin block the mitogenic action of growth factors such as epidermal growth factor (EGF) and insulin-like growth factors I and II (IGF-I and IGF-II, respectively), but it also totally abolished the increase in cell proliferation induced by the steroid hormone 17 beta-estradiol (E2). Maximal inhibition was obtained after 5 days of suramin treatment, and inhibition either was partially reversed by E2, IGF-I, and IGF-II or was not reversible by EGF following removal of drug. In addition, suramin significantly decreased synthesis and secretion of the lysosomal enzyme cathepsin D, which was shown to be associated with a high risk of breast tumor metastasis. These results therefore suggest that, because of its effects on growth and cathepsin D secretion, suramin might be a helpful additional therapeutic tool for breast cancer patients, especially for patients with estrogen receptor-negative tumors which are insensitive to antihormonal strategies. PMID- 1738173 TI - Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. AB - Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity. PMID- 1738175 TI - Tamoxifen: tablet dosage. PMID- 1738174 TI - Ovarian cancer and older women: is treatment less aggressive? PMID- 1738176 TI - Isn't skin cancer preventable? PMID- 1738177 TI - First antisense drug trials planned in leukemia. PMID- 1738178 TI - Mutagens in meat under fire. PMID- 1738179 TI - Late effects of childhood cancer treatment can be life threatening. PMID- 1738180 TI - Is cisplatin a human carcinogen? AB - Traditionally, cisplatin has not been regarded among chemotherapeutic drugs as a carcinogenic risk to humans because it is not a classical alkylating agent. A review of recently published experimental data indicates that cisplatin is mutagenic, clastogenic, capable of inducing cell transformation, able to act as an initiator in classical mouse skin initiation/promotion experiments, and carcinogenic in laboratory animals. Notably, it causes myeloid leukemia in BD IX rats. These observations demonstrate that cisplatin should be considered a potent carcinogen in experimental settings. A review of the literature identified 65 instances of subsequent cancer in patients receiving cisplatin-based chemotherapy for an initial malignancy. The majority of second cancers were acute nonlymphocytic leukemias or myelodysplasia. In only one instance was cisplatin the sole antineoplastic drug given to patients. The routine use of cisplatin in conjunction with other known or suspected human carcinogens makes it impossible to use these anecdotal reports as a basis for assessing cisplatin's carcinogenicity in humans. Two quantitative epidemiologic studies have addressed this question: One suggested that the combination of cisplatin and doxorubicin is leukemogenic in humans, while the other implicated etoposide rather than cisplatin as the leukemogen. Formal epidemiologic studies of appropriate cohorts of cisplatin-treated patients are needed to resolve the question of its carcinogenicity in humans. PMID- 1738181 TI - Trends in cancer mortality in 15 industrialized countries, 1969-1986. AB - BACKGROUND: Assessing trends in cancer provides a means for gauging progress against the disease, estimating future demands for care and treatment, and suggesting clues about shifting causal factors that may account for the more recent changes. PURPOSE: This study was designed to evaluate trends in the major sites of cancer associated with high mortality rates in 15 industrialized countries. To highlight differences among regions, we grouped these countries into six geographic areas: United States, Eastern Europe, Western Europe, East Asia, Oceania, and Nordic countries. In addition, cancer mortality trends in these regions were compared with incidence patterns in the United States. METHODS: Data provided by the World Health Organization were used to evaluate age specific mortality trends from 1969 through 1986 for lung, breast, prostate, stomach, and colorectal cancers and for all other sites considered as a group. We also assembled and analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the same sites and age groups from 1973 through 1986. RESULTS: Over the period 1969 through 1986, recorded cancer mortality in persons aged 45 years and older in the six regions studied has increased for lung, breast, and prostate cancers in most age groups, while the decline in stomach cancer mortality is substantial. The increase in lung cancer deaths in men aged 45-54 years has slowed greatly or reversed in all areas except Eastern Europe and East Asia. Trends for intestinal cancer vary by age and region. For all other sites considered as a group, increases have occurred for persons older than 64 years in most regions. In Eastern Europe, there are disturbingly high rates and rapid increases for several of the major forms of cancer in persons aged 45-54 years. In general, trends for cancer incidence in the United States parallel those for mortality. For intestinal cancer, however, incidence has increased while mortality has declined. CONCLUSIONS: The trends we report cannot be explained solely by changes in cigarette smoking or aging. Other causes of changes in cancer incidence and mortality need to be determined. IMPLICATIONS: The increasing and decreasing trends in mortality from and incidence of cancer that we found are important for health care planning and may also suggest opportunities for research in cancer prevention. PMID- 1738182 TI - Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: a phase I-II study. AB - BACKGROUND: Potentiation of the antitumor activity of fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase, fluorodeoxyuridine monophosphate, and methylene tetrahydrofolate, which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring. Only the levorotatory (6S)-stereoisomer of folinic acid is transformed into active folate cofactors. However, the (6R) stereoisomer of folinic acid is not inert; it was shown to interfere with the (6S) form at the cellular level. PURPOSE: The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out a phase I-II study of 5-FU combined with the (6S)-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. We also determined the plasma pharmacokinetics of folates after intravenous (IV) injection of (6S)-folinic acid at the dose used in this study. METHODS: Treatment consisted of 5-FU (350-550 mg/m2 per day by IV infusion for 2 hours) and (6S) folinic acid (100 mg/m2 per day by IV bolus injection) given for 5 consecutive days; the treatment was repeated every 21 days. Twenty-five patients with advanced colorectal carcinoma, who had had no prior chemotherapy, were evaluated for antitumor activity. The quantity of folates in plasma was measured using a microbiological assay. RESULTS: The median follow-up time was 9 months (range, 3.5-15.2 months). The response rate was 52% (complete response, 12%; partial response, 40%). The median time to disease progression for responding patients was 9.2 months (range, 5.9-15+ months). The estimated probability of survival at 12 months was 73%. Palliative improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects were grade 3 diarrhea, dermatitis, and oral mucositis. Grade 4 toxicity did not occur. Myeloid toxicity was minor. After IV injection, (6S)-folinic acid was rapidly cleared from plasma (mean half-lives: alpha = 7.2 minutes and beta = 126 minutes). The mean concentration of the unchanged compound 2 hours after injection was 5.8 mumol/L. CONCLUSION: The (6S) form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. IMPLICATION: Our results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines. PMID- 1738183 TI - Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group. AB - BACKGROUND: High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. PURPOSE: To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers. METHODS: Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects. RESULTS: After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001). CONCLUSION: This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects. IMPLICATION: The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials. PMID- 1738184 TI - Delayed tumor onset in transgenic mice fed a low-folate diet. AB - BACKGROUND: Transgenic mice carrying the human T-lymphotropic virus type 1 tax1 (transactivator) gene develop peripheral nerve sheath tumors with well characterized times of onset and tissue involvement. PURPOSE AND METHODS: To evaluate the effect of dietary folic acid on age at tumor onset and on the concentration of folate in tissues and tumors, we bred heterozygous transgenic mice and systematically assigned their offspring at weaning (within litters) to a 2 x 2 x 2 factorial arrangement. The three variables studied were 1) the tax1 gene (presence or absence), 2) gender (male or female), and 3) dietary level of folic acid (0.11 or 11.34 mumol folic acid per kilogram of controlled amino acid based diet). Blood and tissues were collected from tumor-bearing transgenic mice (prior to cachexia) and from nontransgenic littermates, matched whenever possible for gender and diet. RESULTS: Transgenic mice fed a diet containing 0.11 mumol of folic acid per kilogram developed tumors significantly later (92.8 +/- 6.4 days) than did those fed a diet containing 11.34 mumol of folic acid per kilogram (71.9 +/- 3.9 days). Folate concentrations in tumors of mice fed the low-folate diet were approximately one third those in tumors of mice fed the higher folate diet. Brain folate concentrations in mice fed the low-folate diet were less than one half those in mice fed the higher folate diet. CONCLUSION: Results show that the onset of spontaneous tumors can be delayed by feeding mice the lowest level of folate adequate to meet nutritional requirements for normal growth. IMPLICATION: Transgenic animal models of human disease offer great potential for evaluating the role of micronutrients in human carcinogenesis. PMID- 1738185 TI - Detection of messenger RNA from O6-methylguanine-DNA methyltransferase gene MGMT in human normal and tumor tissues. AB - BACKGROUND: The level of the DNA repair protein O6-methylguanine-DNA methyltransferase is an important determinant of the response of tumor cells in culture to alkylating nitrosoureas. In these cells, the abundance of messenger RNA (mRNA) is directly correlated with repair activity. PURPOSE: Our purpose was to compare transferase mRNA levels with the repair activity in primary human tumors. METHODS: Human transferase mRNA was measured in tissue samples from brain tumors, normal lung, lung tumors, ovarian tumors, and normal human liver by use of an RNA protection assay with an antisense probe prepared from the cloned gene. RESULTS: Normal and tumor tissue samples from the same patient had similar transferase activity levels, but transferase expression varied widely among tissue samples from different patients. Brain and lung samples, on average, had transferase mRNA levels closer to those in liver samples than their transferase activity levels. In two cases, tissue samples which were transferase deficient by the activity assays were found to lack transferase mRNA. CONCLUSIONS: Deficiencies in transferase activity are due to reduced or absent mRNA transcription or processing. In brain and lung, there may be post-transcriptional control of mRNA expression. The wide interindividual variation in transferase expression is also seen at the transcription level. IMPLICATIONS: These are among the first measures of transferase mRNA expression in primary human tissue. More samples should be examined to extend these observations. PMID- 1738186 TI - Microculture-based chemosensitivity testing: a feasibility study comparing freshly explanted human melanoma cells with human melanoma cell lines. AB - BACKGROUND: The culture of cancer cells has many applications in chemosensitivity testing and new drug development. PURPOSE: Our goal was to adapt simple semiautomated microculture methods for testing the chemosensitivity of melanoma cells freshly recovered from patients' tumors. METHODS: Cells were cultured on a substrate of agarose and exposed continuously to cytotoxic drugs, the effects of which were measured by determining the uptake of [3H]thymidine 4-7 days later. RESULTS: Immunocytochemical staining of cells cultured with 5-bromo-2' deoxyuridine demonstrated that tumor cells were responsible for the measured thymidine incorporation. The effects of cytotoxic drugs were calculated as logarithmic 50% inhibitory concentrations and expressed as divergences from the mean in a log-mean graph. The inhibitory effects of amsacrine, etoposide, doxorubicin, cisplatin, mitomycin C, and fluorouracil were tested. Tumors differed widely in their sensitivity to these drugs, although sensitivity to the three topoisomerase-II-directed agents was highly correlated. Cells from two non neoplastic hematopoietic progenitor cell lines (FT and 32D) showed chemosensitivity patterns distinct from those in the melanoma cells, indicating tissue selectivity. Two established melanoma cell lines, MM-96 and FME, were tested under the same conditions and showed sensitivity typical of at least some fresh specimens. CONCLUSIONS: These results support the validity of melanoma cell lines as models of freshly resected melanoma cells. If successfully applied to other tumor types, such semiautomated approaches could find wide application in routine hospital laboratories for the chemosensitivity testing of patients' tumor cells. PMID- 1738187 TI - Optimal mastectomy timing. PMID- 1738188 TI - Reduced oral etoposide bioavailability in patients with advanced cancer of the head and neck. PMID- 1738189 TI - Soft-laser therapy for iatrogenic mucositis in cancer patients receiving high dose fluorouracil: a preliminary report. PMID- 1738190 TI - Prostate cancer incidence in cimetidine users. PMID- 1738191 TI - Extracellular Tax1 protein stimulates tumor necrosis factor-beta and immunoglobulin kappa light chain expression in lymphoid cells. AB - The human T-cell leukemia virus type I tax1 gene product is responsible for the increased expression of several cytokine and cellular genes that contain NF-kappa B regulatory sequences. Our laboratory has previously demonstrated that purified, extracellular Tax1 protein induced the nuclear accumulation of NF-kappa B binding activity in lymphoid cells. Since HTLV-I infection causes increased levels of lymphotoxin tumor necrosis factor-beta [TNF-beta] and immunoglobulin secretion, we have studied the interaction of NF-kappa B proteins from Tax1-stimulated cells with the TNF-beta and immunoglobulin kappa (Ig kappa) light chain genes. Tax1 induction of NF-kappa B occurred in the presence of cycloheximide, and Tax1 stimulation did not result in increased levels of NF-kappa B or c-rel RNA. These results indicate that new synthesis of NF-kappa B proteins was not required for induction of NF-kappa B-binding activity. With use of the Ig kappa NF-kappa B binding site as a probe, two distinct NF-kappa B gel shift complexes were induced by the Tax1 protein. A slower-migrating complex, C1, was inhibited by the addition of purified I kappa B. In contrast, the faster-migrating C2 complex was not inhibited by I kappa B, but C2 was increased by detergent treatment of cytoplasmic extracts, suggesting that its binding activity was also regulated by an inhibitor. The Tax1-stimulated proteins that interacted with the NF-kappa B binding sites in the Ig kappa and TNF-beta promoters were distinct. A 75-kDa protein preferentially associated with the Ig kappa NF-kappa B-binding site. In contrast, a 59-kDa protein associated with the TNF-beta NF-kappa B-binding site. Tax1 stimulation led to increased levels of TNF-beta and Ig kappa mRNA, as measured by reverse transcription and polymerase chain reaction analysis. These results represent the first experimental evidence that extracellular Tax1 can regulate the expression of endogenous cellular genes. PMID- 1738192 TI - Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. AB - In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages. PMID- 1738193 TI - Identification of a novel gene, Vin-1, in murine leukemia virus-induced T-cell leukemias by provirus insertional mutagenesis. AB - The BL/VL3 radiation leukemia virus is a nondefective retrovirus which induces clonal or oligoclonal T-cell leukemia in mice. To study the role of provirus insertional mutagenesis in the development of these neoplasias, we searched for common provirus integration sites in BL/VL3 radiation leukemia virus-induced tumors. Using cellular sequences flanking a provirus cloned from one of these thymomas, we found that the viral genome was integrated into a common region, designated Vin-1, in a low percentage (5%) of these tumors. The proviruses found in this locus were integrated in the same orientation, close to a CpG-rich island, at proximity of a transcriptional unit encoding a 6-kb RNA. Vin-1 RNA was detected in several organs of the adult mouse. Vin-1 RNA levels were high in tumors having a provirus inserted within the Vin-1 region but were also high in some other tumors whose Vin-1 region was not found to be rearranged. Vin-1 was found to be well conserved among mammalian species and was mapped to mouse chromosome 6, between raf and K-ras-2. Vin-1 appears to be a novel gene which may be involved in tumor development. PMID- 1738194 TI - Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. AB - The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood. PMID- 1738195 TI - Ribozymes which cleave arenavirus RNAs: identification of susceptible target sites and inhibition by target site secondary structure. AB - The development of safe and effective antiviral agents has been a slow process, largely because of the difficulty in distinguishing between virus and host functions; materials toxic to the virus are frequently harmful also to the host in which the agent resides. Recently, techniques which target nucleic acid sequences as a means of reducing gene expression have emerged. This antisense armamentarium includes ribozymes, RNA enzymes which cleave other RNA molecules in a sequence-specific manner. We wish to assess the ability of ribozymes to control animal virus infection. Reasoning that the viruses most vulnerable to ribozyme intervention will be those whose complete life cycle is based on RNA (with no DNA stage), we have begun to develop ribozymes directed toward lymphocytic choriomeningitis virus (LCMV), the prototype of the arenavirus family. Using ribozymes of the hammerhead variety, we have identified several sites on the LCMV genome which can be efficiently cleaved in trans. The efficiency of cleavage is site dependent, and we demonstrate that secondary structure at the target site can abolish ribozyme cleavage. Computer-assisted analysis indicates that much of the LCMV genome may be involved in base pairing, which may render it similarly resistant to ribozyme attack. The few remaining open regions of LCMV lack a GUC target site, on which most studies to date have relied. Here we show that AUC, CUC, and AUU are alternative sites which can be cleaved by trans-acting ribozymes. This finding is important given the aforementioned restriction of available sites, imposed by secondary structure. PMID- 1738196 TI - Tacaribe arenavirus RNA synthesis in vitro is primer dependent and suggests an unusual model for the initiation of genome replication. AB - A Tacaribe virus in vitro system for RNA synthesis was established and found in large part to faithfully reproduce RNA synthesis in vivo. Similar to influenza virus and bunyavirus in vitro systems, this system was also highly dependent on added oligonucleotides. Of the eight tested, only three were active, in the order GpC greater than CpG greater than ApApC. Determination of the 5' ends of the transcripts suggested that the oligonucleotides were acting as primers. In particular, whereas stimulation with CpG (complementary to positions +1 and +2 of the template) led to RNAs whose 5' ends were at position +1 as expected, GpC stimulation led to transcripts whose 5' ends were at position -1 rather than at position +2, as GpC is complementary to positions +2 and +3 of the template. This finding suggests a model for the initiation of genome replication in which pppGpC is first made on the template at positions +2 and +3 but slips backwards on the template so that the 5' end is at position -1 before elongation can continue. PMID- 1738197 TI - Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement. AB - A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication. PMID- 1738198 TI - LRV1 viral particles in Leishmania guyanensis contain double-stranded or single stranded RNA. AB - The 32-nm-diameter spherical viral particles found in the cytoplasm of Leishmania guyanensis CUMC1-1A sediment at 130S and have a buoyant density of approximately 1.4 g/ml in cesium chloride gradients. These particles contain a 5.3-kb double stranded RNA, while single-stranded RNA that corresponds to the viral positive strand is associated with less-dense particles. These results suggest a conservative and sequential mode of LRV1 viral RNA replication that is exemplified by the ScV L-A virus of yeast. PMID- 1738199 TI - Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells. AB - We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1 positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1 transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1 negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome. PMID- 1738200 TI - Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression. AB - We have designed a ribozyme that cleaves human immunodeficiency virus type 1 (HIV 1) RNA in U5 (at nucleotide +115). This ribozyme was tested in vitro and was found to give efficient and specific digestion of RNA containing the HIV-1 U5 sequence. When the U5 ribozyme was placed into the HIV-1 genome, virus replication was suppressed in tissue culture. Introduction of this ribozyme into cells by using an amphotropic retrovirus vector significantly reduced expression of U5-containing RNA in cells chronically infected with HIV-1. Naive T cells were cocultivated with packaging cells that produce defective amphotropic retroviruses containing the U5 ribozyme. These lymphocytes were found to be partially protected from HIV-1 infection. PMID- 1738201 TI - Differential expression of Hz-1 baculovirus genes during productive and persistent viral infections. AB - Hz-1 viral RNA transcription was studied during productive and persistent infections. The RNAs were localized to 10- to 30-kb regions within the viral genome, and the timing of their expression was determined. During productive infections, we detected 101 virus-specific transcripts that could be grouped into three categories by time of appearance. At 2 h postinoculation (p.i.), a total of 34 virus-specific transcripts were detected. An additional 51 and 16 virus specific transcripts appeared between 4 and 6 h p.i. and at 8 h p.i., respectively. After 8 h, no new transcripts were found. Under conditions of persistent infection, we detected only one viral persistency-associated transcript (PAT1). The region of the viral DNA which encodes PAT1 was cloned. During productive infections, three transcripts were derived from this region. Each had the same polarity as PAT1. One of them was of the same size as PAT1 and had similar, if not identical, 3' and 5' ends. This report provides detailed and very useful information concerning sequentially expressed transcripts of the Hz-1 baculovirus. PMID- 1738202 TI - Structure and assembly of hemagglutinin mutants of fowl plague virus with impaired surface transport. AB - Five temperature-sensitive mutants of influenza virus A/FPV/Rostock/34 (H7N1), ts206, ts293, ts478, ts482, and ts651, displaying correct hemagglutinin (HA) insertion into the apical plasma membrane of MDCK cells at the permissive temperature but defective transport to the cell surface at the restrictive temperature, have been investigated. Nucleotide sequence analysis of the HA gene of the mutants and their revertants demonstrated that with each mutant a single amino acid change is responsible for the transport block. The amino acid substitutions were compared with those of mutants ts1 and ts227, which have been analyzed previously (W. Schuy, C. Will, K. Kuroda, C. Scholtissek, W. Garten, and H.-D. Klenk, EMBO J. 5:2831-2836, 1986). With the exception of ts206, the changed amino acids of all mutants and revertants accumulate in three distinct areas of the three-dimensional HA model: (i) at the tip of the 80-A (8-nm)-long alpha helix, (ii) at the connection between the globular region and stem, and (iii) in the basal domain of the stem. The concept that these areas are critical for HA assembly and hence for transport is supported by the finding that the mutants that are unable to leave the endoplasmic reticulum at the nonpermissive temperature do not correctly trimerize. Upon analysis by density gradient centrifugation, cross-linking, and digestion with trypsin and endoglucosaminidase H, two groups can be discriminated among these mutants: with ts1, ts227, and ts478, the HA forms large irreversible aggregates, whereas with ts206 and ts293, it is retained in the monomeric form in the endoplasmic reticulum. With a third group, comprising mutants ts482 and ts651 that enter the Golgi apparatus, trimerization was not impaired. PMID- 1738203 TI - In vitro resolution of poxvirus replicative intermediates into linear minichromosomes with hairpin termini by a virally induced Holliday junction endonuclease. AB - Available evidence suggests that one or more late viral gene products are involved in processing poxvirus replicative intermediates into mature progeny hairpin-terminated genomes. Cloned versions of the Shope fibroma virus (SFV) replicated telomere in the inverted repeat configuration were used as substrates to assay lysates from poxvirus-infected cells for protein fractions that participate in the resolution of the circular substrate plasmid into a linear minichromosome with viral hairpin termini. An activity in a crude protein fraction obtained from vaccinia virus-infected cells at late times during the replicative cycle was capable of accurately resolving all poxviral inverted repeat replicative intermediates tested. The resolved linear products are identical to the products of in vivo resolution and possessed symmetrical nicks which mapped at the borders of the inverted repeat sequence. Strand-specific nicks were also identified, which mapped within the telomere resolution target sequence known to be required for telomere resolution in vivo. The resolving activity that we have identified is specific to virus-infected cells at late times during replication and cleaves cloned poxviral telomeric substrates in a fashion expected of a classic Holliday junction-resolving enzyme in addition to possessing a telomere resolution target-specific nicking activity. Although a Holliday junction-resolving activity would also be expected to play a role in the recombination induced by poxvirus infection, the appearance of the activity described here only after the commencement of viral late protein synthesis suggests that it functions strictly at late times. Other non-viral Holliday junction analogs can also be cleaved by this extract, suggesting that this component of the resolution activity may also play a role in other viral processes that require cleavage of a branched DNA structure. Thus, we have identified a poxviral activity that may be a part of a protein complex which resolves concatemeric replicative intermediates of viral DNA as well as participate in general recombination late during infection. PMID- 1738204 TI - Identification and characterization of an extracellular envelope glycoprotein affecting vaccinia virus egress. AB - Sequence analysis of the vaccinia virus strain Western Reserve genome revealed the presence of an open reading frame (ORF), SalL4R, which has the potential to encode a transmembrane glycoprotein with homology to C-type animal lectins (G. L. Smith, Y. S. Chan, and S. T. Howard, J. Gen. Virol. 72:1349-1376, 1991). Here we show that the SalL4R gene is transcribed late during infection from a TAAATG motif at the beginning of the ORF. Antisera raised against a TrpE-SalL4R fusion protein identified three glycoprotein species of Mr 22,000 to 24,000 in infected cells. Immunogold electron microscopy demonstrated that SalL4R protein is present in purified extracellular enveloped virus particles but not in intracellular naked virus (INV). A mutant virus was constructed by placing a copy of the SalL4R ORF downstream of an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible vaccinia virus promoter within the thymidine kinase locus and subsequently deleting the endogenous SalL4R gene. The growth kinetics of this virus demonstrated that SalL4R was nonessential for the production of infectious INV but was required for virus dissemination. Consistent with this finding, the formation of wild-type-size plaques by this mutant was dependent on the presence of IPTG. Electron microscopy showed that without SalL4R expression, the inability of the virus to spread is due to a lack of envelopment of INV virions by Golgi derived membrane, a morphogenic event required for virus egress. PMID- 1738205 TI - Persistent infection of normal mice with human immunodeficiency virus. AB - In this article, we report the establishment of persistent HIV type 1 infection of normal Swiss mice after a single intraperitoneal injection with high-producing HIV-infected U937 cells. Anti-HIV antibodies were found more than 500 days after the original injection, and p24 antigenemia was detected in approximately 50% of the mice. By polymerase chain reaction (PCR) techniques, HIV-specific gag and env sequences were detected in DNA samples from peripheral blood mononuclear cells (PBMC) and peritoneal cells of seropositive mice 300 to 500 days after inoculation with HIV-infected cells. These DNA samples did not contain human DNA sequences, as determined by PCR analysis using primers and the probe for the HLA DQ alpha gene. Low levels of p24 and detectable human reverse transcriptase activity were found in cultures of PBMC and peritoneal macrophages. Cocultivation of PBMC, peritoneal cells, and spleen cells with human uninfected U937 or CEM (a T lymphoma cell line) cells resulted in HIV infection of the target cells, as determined by PCR analysis and/or p24 assays. The intravenous injection of untreated Swiss mice with the PBMC from PCR-positive mice resulted in the development of an increasing antibody response to HIV in the recipient animals. Together these results indicate that cells from seropositive Swiss mice were persistently infected with HIV and were capable of producing infectious virus. The development of persistent HIV infection in an immunocompetent mouse may represent the starting point for further studies aimed at defining the host mechanisms involved in the restriction of virus replication, defining the pathogenesis of HIV infection, and testing antiviral compounds and vaccines. PMID- 1738206 TI - Binding of a host cell nuclear protein to the stem region of human immunodeficiency virus type 1 trans-activation-responsive RNA. AB - Human immunodeficiency virus type 1 (HIV-1) transcription is regulated by both viral and host cell factors. Although the viral trans-activator protein, Tat, and its cis-responsive element, trans-activation-responsive (TAR) RNA, have been identified and characterized, the mechanism of HIV-1 transcriptional regulation has not been satisfactorily described. Whereas Tat is necessary to activate transcription, additional factors, derived from the host cell, are important in regulating HIV-1 transcription. To identify such host cell-specific factors, we used an RNase protection mobility shift assay and UV cross-linking to detect a 140-kDa HeLa cell nuclear protein that binds specifically to TAR RNA. By extensive mutational analysis, we determined that the binding of this protein is dependent on both the sequence and the structure of the TAR RNA stem region. Other groups have shown that the production of prematurely terminated transcripts from the HIV-1 promoter is also dependent on the sequence and structure of the TAR RNA stem. This correlation with our results suggests that the TAR RNA stem binding protein is involved in the production of prematurely terminated transcripts from the HIV-1 promoter and in the regulation of HIV-1 gene expression. PMID- 1738207 TI - Irreversible modification of measles virus RNA in vitro by nuclear RNA-unwinding activity in human neuroblastoma cells. AB - The matrix (M) gene of a measles virus (MV) variant passaged in IMR-32 human neuroblastoma cells displays numerous uridine-to-cytosine transitions called biased hypermutation. Using an in vitro assay, we show that IMR-32 cells contain high levels of an activity which unwinds and irreversibly alters the base pairing of double-stranded RNA synthesized from the M gene of MV. This activity is found exclusively in the cellular nucleus and is present at a lower level in African green monkey kidney Vero cells. Experiments with mixed cell extracts suggest that the low activity in Vero cells is not due to inhibitory factors. These findings support the hypothesis that this RNA-modifying and -unwinding activity is responsible for biased hypermutation of MV strains that infect the central nervous system. Possible functions of this neural cell activity and implications for central nervous system disorders are discussed. PMID- 1738208 TI - A chimera of EBNA1 and the estrogen receptor activates transcription but not replication. AB - DNA replication from the plasmid origin of replication of Epstein-Barr virus requires one viral protein, EBNA1. This protein also acts as a transcriptional activator. Mutational analyses of EBNA1 have led to the conclusion that it supports transcription and DNA replication similarly. Such analyses have not probed the DNA-binding domain of EBNA1. To test whether domains of EBNA1 specifically required for either transcription or replication lie within its DNA binding domain, we constructed a functional transcriptional activator by placing the EBNA1 DNA-binding domain in the context of the activation domains of the estrogen receptor. This hybrid protein did not support DNA replication, which indicates that the DNA-binding domain does not contain a replication-specific domain that can function along with heterologous transcriptional activating domains. PMID- 1738209 TI - Mutational analysis of conserved N-linked glycosylation sites of human immunodeficiency virus type 1 gp41. AB - Amino acid substitutions were introduced into four conserved N-linked glycosylation sites of the human immunodeficiency virus type 1 envelope transmembrane glycoprotein, gp41, to alter the canonical N-linked glycosylation sequences. One altered site produced a severe impairment of viral infectivity, which raises the possibility that N-linked sugars at this site may have an important role in the human immunodeficiency virus type 1 life cycle. PMID- 1738211 TI - Effect of short-chain fatty acids on colonic function and structure. AB - Short-chain fatty acids (SCFA), fermentation products of fiber, are believed to play a role in intestinal adaptation. Although the administration of fiber or the infusion of SCFA has been shown to cause colonic growth, studies have been done primarily in enterally fed animals. In addition, the effects of SCFA on absorptive function have not been determined. Adult male rats were maintained on total parenteral nutrition (TPN) and, in addition, received either 150 mmol/L of saline or 150 mmol/L of SCFA mixture (60:25:15, acetate:propionate:butyrate) into the proximal colon. One week later, the in vivo absorption of water, electrolytes, and 20 mmol/L of butyrate was measured. After the rats were killed, parameters of colonic mass were determined. SCFA infusion into the colon had no significant effect on absorptive function. However, significantly greater mucosal height (p less than .01) and mucosal DNA (p less than .05), were observed. Although SCFA has a modest effect on colonic structure, they do not influence absorptive function in TPN rats. PMID- 1738210 TI - Efficient replication of human immunodeficiency virus type 1 requires a threshold level of Rev: potential implications for latency. AB - The Rev protein of human immunodeficiency virus type 1 (HIV-1) is essential for the expression of the structural genes of HIV-1. To determine whether a functional threshold level of Rev is required to allow efficient HIV-1 replication, CD4-positive HeLa cells, constitutively expressing a Rev-deficient provirus, were transfected with various quantities of a Rev-expressing plasmid. Compared with the quantity of the Rev-producing plasmid transfected, HIV-1 replication was distinctly nonlinear as measured by HIV-1 p24 antigen and HIV-1 specific RNA production. A quantitative RNA polymerase chain reaction (PCR) demonstrated that Rev mRNA expression was linearly correlated with the quantity of Rev-expressing plasmid which was transfected into these cells. These data suggest that a critical threshold of Rev is required for a highly productive HIV 1 infection. This threshold level of Rev may be involved in the generation and maintenance of HIV-1 proviral latency. PMID- 1738212 TI - Nutritional and metabolic response to acute spinal-cord injury. AB - The metabolic response to complete spinal cord injury was prospectively studied in 10 patients with Frankel class A spinal cord injury. Weekly excretory and balance studies profile the changes in nitrogen, calcium, and 3-methylhistidine excretion in relation to body weight and metabolic rate. The initial resting energy expenditures were 10% below what was predicted, and body weight decreased by 10%. Nitrogen excretion paralleled the changes in body weight. Calcium excretion increased for 3 weeks and reached a plateau 150% above baseline. Our results chronicle the magnitude of metabolic response to spinal shock. Comparison with reported values shows this response exceeds that seen in immobilized patients. Nitrogen excretion rose to levels seen in highly stressed patients and must be considered in the management of patients with acute spinal-cord injury. PMID- 1738213 TI - Effect of intravenous fat on cholecystokinin secretion and gallbladder motility in man. AB - During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction. PMID- 1738214 TI - Comparison of tolerance and nutritional outcome between a peptide and a standard enteral formula in critically ill, hypoalbuminemic patients. AB - Dipeptides have been reported to be more efficiently absorbed from the gastrointestinal tract than free amino acids. The objective of this study was to compare prospectively a peptide enteral formula (PEF) with a standard enteral formula (SEF) for tolerance and nutritional outcome in acutely injured, hypoalbuminemic (less than 3.0 g/dL) patients who require enteral nutrition support. The prevalence of diarrhea and elevated gastric residuals was assessed daily. Prealbumin, transferrin, colloid oncotic pressure, Prognostic Nutritional Index, and nitrogen balance were measured on days 0, 5, and 10 of enteral nutrition support. Forty-one patients received 345 days of enteral nutrition support. Prevalences of diarrhea and elevated gastric residuals were similar between groups. Prealbumin increased and the Prognostic Nutritional Index decreased significantly from baseline at day 10 in both groups. Transferrin increased in both groups, but not significantly. Colloid oncotic pressure increased significantly from baseline at days 5 and 10 in the SEF group and day 10 in the PEF group. Nitrogen balance increased significantly from baseline at days 5 and 10 in each group. The only significant difference between groups was for nitrogen balance at day 10, which was higher in the SEF group. We conclude based upon our selected measurements of tolerance and nutritional outcome PEF seems to offer no advantage over SEF in acutely injured, hypoalbuminemic patients. PMID- 1738215 TI - Protein malnutrition alone and in combination with endotoxin impairs systemic and gut-associated immunity. AB - Because protein-malnourished or endotoxemic patients are at an increased risk of developing nosocomial infections, this study was performed to investigate the effects of protein malnutrition and endotoxemia, alone and in combination, on systemic and intestinal immunity. Protein malnutrition was created by feeding the animals a solid diet containing 0.03% protein. Subgroups of these protein malnourished mice were killed after being challenged with saline or endotoxin on days 0, 7, 14, or 21. At death, the animals were weighed, tissues were harvested for histologic analysis (ileum, mesenteric lymph node [MLN], liver, and spleen), mitogen responsiveness (MLN, Peyer's patches, and spleen), and xanthine oxidase measurements (ileum and cecum). Separate groups were evaluated for survival. Both the saline and endotoxin-challenged mice had lost about 30% of their body weight after 21 days on the low-protein diet. The protein-malnourished mice were more susceptible to endotoxin-induced mortality (70% at 21 days) than the normally nourished mice (0%) (p less than .001). The mitogen responsiveness of the protein malnourished mice to the T-cell mitogens (PHA and Con-A) progressively decreased the longer the mice were protein malnourished, and this decreased in blastogenic responsiveness was associated with histologic evidence of lymphoid atrophy. In contrast, the blastogenic response to the primarily B-cell mitogen, PWM, was largely preserved. The endotoxin challenge further depressed the immune state of mice tested after 0, 7, or 14 (but not 21) days of protein malnutrition. Thus, both protein malnutrition and endotoxin impaired systemic and gut-associated immune responsiveness to mitogens. However, in the protein-malnourished mice, the degree of immune suppression did not correlate with endotoxin-induced mortality. PMID- 1738216 TI - Use of even-numbered carbon atom dicarboxylic salts in parenteral nutrition as fuel substrate. AB - Sebacic acid (C10), a saturated, straight-chain dicarboxylic acid with 10 carbon atoms in disodic salt form, was given intravenously to two groups of healthy male volunteers in order to evaluate its possible use in total parenteral nutrition. The first group, composed of six subjects, received 1000 mg of sebacate as a bolus; six other subjects (second group) received 10 g of sebacate dissolved in 500 mL of double-distilled water at an infusion rate of 3.33 g/h over 3 hours. The serum sebacate data for each subject were analyzed by computer, using biexponential fit corresponding to a 2-compartment open model. The distribution half-life (t1/2) was 0.34 +/- 0.06 hour and the elimination phase was rather rapid (Ke = 2.10 +/- 0.38/h); the volume of the central compartment was 2.79 +/- 0.54 L and the volume of tissue compartment 3.72 +/- 0.14 L. These data showed a good tissue fixation of sebacate. The plasma clearance was evaluated to be 5.96 +/- 2.19 L/h and the renal clearance was 19.22 +/- 10.69 L/h, indicating that a tubular secretion of C10 takes place. The serum concentration of sebacate raised to the maximal value at the end of the infusion (180 minutes), corresponded to 480.50 +/- 43.02 micrograms/mL. Respiratory and metabolic parameters were evaluated by indirect calorimetry from the beginning of the infusion for 210 minutes. The O2 consumption (VO2 mL/min per square meter) remained essentially unchanged throughout the experiment (from 154.3 +/- 28.3 at 0 to 155.3 +/- 39.5 at time 180 minutes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738217 TI - Effect of rate of enteral nutrient supply on gut mass. AB - Early enteral feeding after injury is important for maintenance of gut integrity. However, enteral nutrients are frequently administered at low rates because of decreased gastrointestinal motility. These low rates are said to "maintain the gut." This study was performed to evaluate the effect of rate of enteral nutrient delivery on gut mass. Six male Sprague-Dawley rats had no surgery and served as controls (ad libitum rat chow diet). Twenty-four male Sprague-Dawley rats underwent abdominal surgery for placement of gastroduodenal feeding tubes (tip located 2 cm into intestine from pylorus) and were randomized (n = 6 per group) to ad libitum rat chow, 1/2 strength peptide diet (Reabilan HN, RHN) at 1 mL/h (1/2RHN-1 mL), full-strength peptide diet at 2 mL/h (RHN-2 mL), or full-strength peptide diet at 4 mL/h (RHN-4 mL). These diets supplied approximately 30%, 13%, 50%, and 100% of rat recommended daily allowances. The control animals gained weight (38 +/- 3 g over 5 days) whereas all postsurgery animals lost weight. Weight loss was greatest in the 1/2 RHN-1 mL (-55 +/- 3 g over 5 days) and RHN-2 mL (-52 +/- 6 g over 5 days) groups compared with the RHN-4 mL animals (-41 +/- 5 g over 5 days). All animals fed liquid enteral diets had reduced gut weights compared with chow-fed animals. Gut weights did not differ between control and postsurgery ad libitum chow animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738218 TI - Effect of short-chain fatty acids on the human colonic mucosa in vitro. AB - Fermentable dietary fiber components are known to stimulate colonic crypt proliferation. As these compounds are rapidly degraded to short-chain fatty acids (SCFAs) by the anaerobic microflora, the hypothesis was tested that this trophic effect of fiber may be mediated by SCFAs. Biopsies were taken from normal cecal mucosa of 45 individuals during routine colonoscopy. They were incubated for 3 hours with sodium salts of SCFAs at physiological concentrations (three SCFAs = acetate 60 mmol/L + propionate 25 mmol/L + butyrate 10 mmol/L; acetate 60 mmol/L; propionate 25 mmol/L; butyrate 10 mmol/L) or equimolar NaCl (control). Cell proliferation was measured autoradiographically by subsequent pulse labeling with [3H]thymidine (1 hour). The labeling index (number of labeled cells divided by the total number of cells) was computed for the crypt as a whole and for five equal crypt compartments (compartment 1 = crypt base, compartment 5 = crypt surface). Cecal crypt proliferation was raised significantly in all incubation experiments with SCFAs. Butyrate (10 mmol/L, increase + 89%) and propionate (25 mmol/L, + 70%) were as effective in stimulating proliferation as the combination of three SCFAs (+103%), although the effect of acetate (+31%) was minor. Increasing the butyrate concentration to 25 mmol/L or 60 mmol/L did not result in a further increase of cell labeling. SCFAs stimulated proliferation in the basal three crypt compartments only. An expansion of the proliferative zone to compartments 4 and 5 was not observed. SCFAs, especially butyrate and propionate, are luminal trophic factors for the cecal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738219 TI - Concurrent administration of albumin with total parenteral nutrition in sick newborn infants. AB - The effects of concurrent administration of albumin with total parenteral nutrition were studied in 12 premature newborns (birth weight 1.26 +/- 0.1 kg [mean +/- SEM] and gestational age 30 +/- 0.8 weeks [mean +/- SEM]) compared with a control group of 12 premature newborns (birth weight 1.17 +/- 0.2 kg and gestational age 29 +/- 0.1 weeks) who received total parenteral nutrition. All newborns had a plasma albumin level below 3 g/dL and were in cardiorespiratory distress requiring assisted ventilation. Albumin supplementation of total parenteral nutrition resulted in a sustained increase in serum albumin concentration as well as increased mean arterial blood pressures in the study group. Slow albumin infusion had no observed effect on the severity of respiratory distress. Study group infants regained birth weight earlier than control group infants. These data suggest that the concurrent administration of albumin may be clinically beneficial in critically ill newborn infants. PMID- 1738220 TI - Glucose metabolism and thermogenesis during glucose and insulin infusion in severely underweight patients. AB - This study investigates the effects of gross loss of body weight on glucose disposal (GD), storage (GS), oxidation (GO), and the thermogenic response (TR) during hyperinsulinemic euglycemic glucose infusion in 9 underweight but nourished patients (UP) and in 3 of the patients after weight gain (WGP). In UP, baseline metabolic rate (MR) was 4.1 +/- 0.2 kJ/min and respiratory exchange ratio (RER) 0.97 +/- 0.02. During the final 30 minutes of hyperinsulinemia MR rose by 0.32 +/- 0.07 kJ/min (p less than .01) and RER rose to 1.09 +/- 0.03 (p less than .01). GD was 61 +/- 3 mumol/kg per minute, GO 35 +/- 1 mumol/kg per minute, and GS 26 +/- 4 mumol/kg per minute. The energy cost of glucose storage as glycogen was 0.15 kJ/min, and as lipid was 0.2 kJ/min. In WGP baseline MR was 4.5 +/- 0.4 kJ/min and RER was 0.91 +/- 0.03. During hyperinsulinemia MR rose by 0.63 +/- 0.2 kJ/min, RER rose to 0.93 +/- 0.02, GD was 53 +/- 4 mumol/kg per minute, GO was 30 +/- 3 mumol/kg per minute, and GS was 23 +/- 1 mumol/kg per minute. The energy cost for this glucose storage was 0.22 kJ/min. Therefore, during hyperinsulinemia in UP, GD, and TR are similar, but GO is greater and GS is less than previously reported in healthy subjects. However, this TR is entirely accounted for by the energy cost of glucose storage with no evidence of facultative thermogenesis. In WGP, all responses were similar to those in healthy subjects, and the TR was in excess of that required of the energy cost of glucose storage. PMID- 1738221 TI - Platelet glutathione peroxidase activity in long-term total parenteral nutrition with and without selenium supplementation. AB - Selenium (Se) is not routinely included in total parenteral nutrition (TPN) solution; thus, patients receiving long-term TPN may be at risk of Se deficiency, which may cause fatal cardiomyopathy. Platelet glutathione peroxidase (GSH-Px) activity, as well as Se levels and GSH-Px activity in plasma and erythrocytes during prolonged TPN, was measured in six patients with chronic gastrointestinal disease. During the time course of TPN, Se administration was discontinued for 12 weeks, and then resupplemented for another 12 weeks. Before the study period, all Se indices had been maintained within the normal range. After discontinuation of Se supplementation, a significant decrease in platelet GSH-Px activity was observed after 1 week (from 64 +/- 7 [mean +/- SD] to 39 +/- 5 U/g of protein). After resupplementation, it increased after 1 week (from 44 +/- 9 to 65 +/- 10 U/g of protein). Plasma Se indices significantly changed within 3 weeks after withdrawal and reintroduction of Se (Se: from 136 +/- 28 to 75 +/- 14 and from 61 +/- 22 to 125 +/- 33 micrograms/L; GSH-Px: from 236 +/- 50 to 140 +/- 36 and from 128 +/- 32 to 220 +/- 64 U/L). Erythrocyte Se indices showed no significant changes during the study period. The results demonstrate that platelet GSH-Px activity is the most sensitive index of Se status in TPN patients. PMID- 1738222 TI - Equal aspiration rates from postpylorus and intragastric-placed small-bore nasoenteric feeding tubes: a randomized, prospective study. AB - Postpylorus delivery of enteral feeding is perceived by many experts to be safer than intragastric delivery. To test this assumption, patients with similar Glasgow Coma Scores were given identical enteral formulas continuously via a 10 French nasoenteric tube, placed into the stomach or beyond the second portion of the duodenum. Observations were made for attainment of desired nutrition, bowel changes, and clinical signs of aspiration. Radiographs of the chest and abdomen were obtained every 3 days. If a tube migrated out of a chosen location, it was replaced. Thirty-three patients were studied. Seventeen patients were fed into the stomach and 16 patients were fed postpylorus. The mean duration of enteral feeding was 11.8 days for the gastric group and 10.9 days for the postpylorus group (p = NS). The time to deliver the desired kilocalories was 3.33 and 2.77 days (p = NS) for gastric and postpylorus-fed patients. Tubes displaced similarly in each group, gastric 0.647, postpylorus 0.750 per duration of feeding (p = NS). Chest radiographs met the criteria for aspiration pneumonia in 31.3% of gastric and 40% of postpylorus-fed patients (p = NS). Together, these data indicate that complications from enterally fed patients are equally common whether the distal port of the feeding tube is in the stomach or beyond the second portion of the duodenum. PMID- 1738223 TI - Emulsion stability in total nutrient admixtures containing a pediatric amino acid formulation. AB - Emulsion stability of total nutrient admixtures containing TrophAmine amino acid injection admixed with Intralipid, Nutrilipid, and Liposyn II was studied. High and low electrolyte concentrations were added to each total nutrient admixture before storage at 4 degrees C for 48 hours then at 20-22 degrees C for 24 hours. Stability studies were also performed on total nutrient admixtures containing higher concentrations of fat emulsion and total nutrient admixtures with added cysteine hydrochloride and carnitine. High electrolyte concentrations only were added to these total nutrient admixtures before being stored refrigerated for 24 hours then at room temperature for 24 hours. Visual assessment, pH determination, and particle size analysis were performed immediately after compounding and after refrigerated and room temperature storage. Particle size was assessed by measuring the mean diameter of the fat emulsion and the percent of oil volume in particles greater than 5 microns. Repeated-measures analyses of variance were used to determine significance of type or concentration of fat emulsion, electrolyte concentrations, or time on mean diameter or percent particles greater than 5 microns. There were minimal changes in pH values over time. Creaming was observed in all total nutrient admixtures at all sampling times except time zero. This was reversible upon agitation. Results of particle size analysis over time indicated little change in mean diameter or percent particles greater than 5 microns. These minimal changes did not seem to be clinically significant. It is concluded that total nutrient admixtures prepared with this pediatric amino acid formulation are stable when prepared and stored as reported. PMID- 1738224 TI - Effects of various enteral feeding products on postprandial blood glucose response in patients with type I diabetes. AB - These studies were performed to evaluate the postprandial blood glucose responses to a variety of differently formulated enteral feeding products in patients with type I diabetes. Eleven subjects with type I diabetes were evaluated in three studies, all using a Biostator (artificial endocrine pancreas) that delivered a small, basal amount of insulin and measured blood glucose levels. Subjects consumed 20 mL of the assigned formula every 15 minutes for the 240 minutes of the study. Study 1 evaluated the response to each of five products: Glucerna, Enrich, Ensure HN, Pulmocare, and Compleat Modified. When the postprandial blood glucose response to Glucerna was greater than when its research formulation (EN 8715) had been tested in 1988, studies 2 and 3 were undertaken to assess why this discrepancy occurred. Study 2 compared stored EN-8715 to Glucerna and study 3 compared frozen and thawed vs nonfrozen EN-8715, because of a concern that the original product had been frozen during shipping. In study 1 the glucose response (assessed as area under the glucose curve) correlated with the grams of carbohydrate present in the enteral feeding formula (r = .58, p = .002). The presence or absence of fiber, in the form of soy polysaccharide, did not affect the glucose response. Glucerna produced a significantly lower blood glucose response than did Enrich, Ensure HN, or Compleat Modified, although this response was greater than the response to EN-8715 in 1988. However, in study 2 no differences were found between stored EN-8715 and Glucerna and in study 3, freezing and thawing was not found to significantly alter the glucose response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738225 TI - Spontaneous partial fracture of the catheter of a totally implantable subcutaneous infusion port. AB - A totally implantable subcutaneous infusion port was inserted via the left subclavian vein with peel-away sheath in a 45-year-old male patient receiving home parenteral nutrition. Sixteen months after implantation, the patient noted pain in his left clavicular region during home infusion. This was found to be due to the leakage of infusion fluid resulting from partial fracture of the catheter at the level where the catheter passed between the clavicle and first rib. Because the fracture was partial, the catheter did not embolize to the heart or large vessels. Although subcutaneous infusion ports afford patients greater freedom and the ability to lead a more active life than do external catheters, it is emphasized that there may be the risk of spontaneous catheter fracture in patients using subcutaneous infusion ports. PMID- 1738226 TI - The Prognostic Inflammatory and Nutritional Index in traumatized patients receiving enteral nutrition support. PMID- 1738227 TI - Total parenteral nutrition and tumor metastases. PMID- 1738228 TI - Composition of fat in enteral diets can influence outcome in experimental peritonitis. PMID- 1738229 TI - Special report from ASCN/A.S.P.E.N. Working Group on Standards for Aluminum Content of Parenteral Nutrition Solutions. PMID- 1738230 TI - Phenytoin and enteral feeding. PMID- 1738231 TI - Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis. AB - The ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis. PMID- 1738232 TI - Marginal mandibulectomy for carcinoma of the floor of the mouth. AB - Resection of primary tumors of the floor of the mouth mandates consideration of the management of the mandible which may be either involved by direct invasion or by close proximity. Segmental mandibulectomy can usually be performed when the tumor is either massive or directly invading the mandible. However, the cosmetic and functional results of segmental mandibulectomy are unsatisfactory. Whenever the tumor is close to the mandible or adherent to the periosteum, consideration should be given to marginal mandibulectomy. Over a period of 8 years, we have treated 65 patients with carcinoma of the floor of the mouth. Of these, 22 underwent marginal mandibulectomy. The number of patients staged T1, T2, and T3 were 4, 13, and 5, respectively. Most had oblique marginal mandibulectomy including the resection of the upper rim and medial cortex of the mandible. Vertical or horizontal mandibulectomy was rarely used. In each patient the preoperative workup included dental X-rays, panoramic films, and computerized tomography (CT) scan of the head and neck. The decision as to the extent of mandibulectomy was made primarily based on the clinical judgement. Seven patients underwent marginal mandibulectomy through the open mouth. However, in the remaining 15 patients, the cheek flap approach was utilized. The defect following marginal mandibulectomy was reconstructed either with split thickness skin graft, tongue flap, or myocutaneous flap. Small defects were left open to heal by granulation and secondary intention. Split thickness skin grafts healed very well over the surface of resected mandibles. Good local tumor control was achieved at the primary site and the functional and cosmetic results were excellent. PMID- 1738233 TI - Intravenous nitrogen mustard given immediately after mastectomy: possible effect on local recurrence. AB - A small group of patients with Stage I and II ductal breast carcinomas were treated with intravenous nitrogen mustard the day of mastectomy and the first two postoperative days. Long term follow-up revealed that only one patient developed isolated local recurrence, a rate much lower than usually reported. It is possible that early use of chemotherapy could reduce local recurrences in the recently traumatized tissue. PMID- 1738234 TI - Carcinoid tumors and inflammatory bowel disease. AB - Three cases are described in which carcinoid tumors arose in previously established inflammatory bowel disease: two were in the ileum in cases of Crohn's disease, and one was in the rectum in a case of ulcerative colitis. Review of this association in the literature suggests that it may be more than fortuitous. PMID- 1738235 TI - Distribution of histologic subtypes and sex ratio in various primary sites of lymphocytic lymphoma. AB - To examine the distribution of histologic subtypes and sex ratio in each primary site of lymphoma, 1,169 histologically proven cases of lymphocytic lymphoma were analyzed. The location of tumor was nodal in 615(53%) and extranodal in 517(44%), patients with the gastrointestinal tract being the most common. The incidence was predominantly in males for all histologic types and in nodal and extranodal sites, except for a predominance of females in extranodal lymphoplasmacytic(Lp cytic), lymphoplasmacytoid(Lp-cytoid) tumors. Frequency of the Lp-cytic/Lp-cytoid type among all types of lymphoma in females was about 2.7 times more frequent in extranodal than in nodal sites. The most striking example was thyroid lymphoma in which the frequency of Lp-cytic/Lp-cytoid type was 36% in female and 0% in male patients. Including this type of lymphoma, frequency of low grade lymphoma in females was higher in extranodal sites than in nodal sites. PMID- 1738236 TI - Merkel cell carcinoma: report of two cases and clinical considerations. AB - We present the clinical and pathological features of two cases of facial Merkel cell carcinoma (MCC) and a critical reappraisal of the literature on this subject. Among patients with this presentation of a rare neoplasm, the disease is very often localized (local or locoregional growth, without distant metastases). Radiotherapy seems to be highly effective in obtaining local control and possibly cure, even when used as the sole treatment method; prompt regression of the neoplastic masses has been observed in both the cases we treated. One of them, and many of those reported in the literature and treated with radiotherapy alone or combined with surgery, achieved long-term survival. PMID- 1738237 TI - Malignant granular cell tumor of the breast. AB - A primary malignant granular cell tumor (MGCT) in the breast is presented. The tumor showed mitoses, pleomorphism, necrosis and regional lymph node spread. While local excision is the best form of treatment, MGCT can spread rapidly to lymph nodes, lungs, liver, and bone. This lesion is an uncommon primary malignancy of breast with only 4 other cases reported. PMID- 1738238 TI - The value of prognostic factors in selecting node-negative breast cancer patients for adjuvant therapy. PMID- 1738239 TI - Cancer control in developing countries. PMID- 1738240 TI - Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma. AB - Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma. Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals. In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival. In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%. When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma. PMID- 1738241 TI - Increased drug resistance of cultured human cancer cell lines in three dimensional cellular growth assay using collagen gel matrix. AB - We have conducted a three-dimensional cellular growth assay using collagen gel matrix with an endpoint of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay, on four human gastric and colonic cancer cell lines. Three-dimensionally growing cells in collagen gel matrix were 2- to 180 fold more resistant to mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin than those in monolayer culture, and these resistances were increased further when the cells increased their three-dimensionality. Furthermore, the influence of fibroblasts in the collagen gel matrix on the chemosensitivity of cancer cells was less than that in monolayer culture. Since this new assay using collagen gel matrix with an endpoint of the MTT assay was able to detect the increase of drug resistance of human cancer cell lines by three-dimensional cellular growth using a simple and convenient procedure, it was considered to be more useful than conventional monolayer cultures for evaluating the chemosensitivity of cancer cells. PMID- 1738242 TI - Total gastrectomy: nutritional status after different reconstruction techniques. An experimental study. AB - The authors report their experimental studies on early nutritional changes in 30 gastrectomized rats where intestinal continuity was restored by three different reconstruction methods, i.e., exclusion of the duodenum from alimentary transit (Sweet-Allen method), or duodenal recanalization (Longmire method) or double duodenal and jejunal recanalization (Moricca method). Ten sham operated rats were used as controls. Results showed that the group of rats which underwent Longmire's reconstruction presented better nutritional parameters (body weight gain, daily food intake, feeding efficiency, albuminemia) than the Moricca and Sweet-Allen reconstruction groups. These results became statistically significant when follow up was extended to 18 months by using an actuarial method. However, perioperative mortality rate was highest in the Longmire reconstruction group. PMID- 1738244 TI - Patents in biotechnology. PMID- 1738243 TI - Fifteen years of research of bioactive alkaloids. PMID- 1738245 TI - Heterotrimeric GTP-binding proteins: an expanding family of signal transducers. PMID- 1738246 TI - [New view on rehabilitation procedures promises major economic and humanitarian benefits]. PMID- 1738247 TI - [Valuable tests for students with foreign preclinical education]. PMID- 1738248 TI - [Information-based adjustment of sex education clinics for adolescents]. PMID- 1738249 TI - [Do not reduce the competence level of the general psychiatric public care]. PMID- 1738250 TI - [Sick-listed but active]. PMID- 1738251 TI - [Weak hands demand specially adjusted drug packages]. PMID- 1738252 TI - [Adenotomy is of certain significance in recurrent otitis]. PMID- 1738253 TI - [Cognitive psychotherapy in the elderly with anxiety depressive disorders is effective]. PMID- 1738254 TI - [Time pressure is a problem for a sex education project]. PMID- 1738255 TI - [For how long have rheumatic diseases existed? Pictorial art as evidence]. PMID- 1738256 TI - [Considerable variations in diagnostic and therapeutic routines. Medical education on asthma treatment should be improved as a study from emergency departments indicates]. PMID- 1738257 TI - [Transplantation of the small intestine can be suitable in patients with pseudo obstruction]. PMID- 1738258 TI - [The largest institution for patients with tuberculosis in Sweden had its own cemetery for the victims of the disease]. PMID- 1738259 TI - [A commentary on vision-threatening retinal changes in diabetes. Consensus conferences should be continued. They are valuable for all participants]. PMID- 1738260 TI - [Physicians and writers in Scandinavia. Emil Aarestrup--poet of love and death]. PMID- 1738261 TI - [Sclerotherapy in bleeding stomach ulcers--an effective therapeutic method]. PMID- 1738262 TI - [Inconsistent on amalgam]. PMID- 1738263 TI - [Difficult to understand criticism against curettage-cryosurgery in basalioma]. PMID- 1738264 TI - [Impermeable equipment should be used for intravenous infusions of nitroglycerin]. PMID- 1738265 TI - [Knowledge about metabolic capacity is important in drug therapy]. AB - Genetic polymorphisms are common and are also found for drug metabolising enzymes such as acetyltransferase and two distinct cytochrome P-450 isoenzymes that catalyse the oxidative metabolism of the model drugs debrisoquine and S mephenytoin respectively. Thus, individual metabolic activity can be categorised as slow or rapid. The metabolism of a number of drugs has been shown to cosegregate with that of either of these substrates. In subjects with slow metabolism of a certain drug, its effects might be enhanced due to increased concentrations either of the drug itself or of its active metabolite(s). In practice, knowledge of a patient's debrisoquine metabolic phenotype is an advantage when prescribing tricyclic antidepressants and neuroleptics, as the drug concentration will be considerably higher in slow metabolisers than in the average patient. Codeine has no analgesic effect in slow metabolisers of debrisoquine, probably due to deficient metabolism to morphine. Pharmacogenetic data can also be utilised as an aid in interpreting the drug concentrations obtained in therapeutic drug monitoring programmes. The metabolism of diazepam, omeprazol, and proguanil is associated with the capacity to oxidise S mephenytoin. Proguanil requires metabolic activation before it has any effect on the malaria parasite and this reaction seems severely impaired in slow metabolisers of S-mephenytoin. So far, no unequivocal relationship has been established as existing between drug oxidation phenotypes and spontaneous disease manifestations. The potential clinical importance of polymorphic metabolic drug elimination needs to be taken into consideration in assessing drugs. PMID- 1738266 TI - [Significant difference in sterilization frequency in different counties 15 years after the introduction of the new legislation]. PMID- 1738267 TI - [A functioning classification system for primary health care now exists]. PMID- 1738268 TI - [The physician Linne. A far-seeing observer--the first practitioner of occupational medicine in Sweden]. PMID- 1738269 TI - [Hyperhomocysteinemia--a new risk factor for vascular diseases?]. PMID- 1738270 TI - [Hyponatremia can indicate tuberculous meningitis]. PMID- 1738271 TI - [Unreasonable regulations on issuing of death certificates]. PMID- 1738272 TI - [Forensic examination of HIV-infected persons: knowledge of risk factors can prevent suicide]. PMID- 1738273 TI - [159 cases of renal adenocarcinoma. Good prognosis with nephrectomy if the tumor is intracapsular]. PMID- 1738274 TI - [We have much to learn about the treatment and prevention of post-traumatic stress]. PMID- 1738275 TI - [Experiences of the Stockholm County Council. Concentration on education in psychological and social disaster planning is a good investment]. PMID- 1738276 TI - [Insufficient documentation is a serious problem for quality assurance of nursing care]. PMID- 1738277 TI - [A special study helps to find hidden shortages of health services to the patients]. PMID- 1738278 TI - [Physicians and writers in Scandinavia. Paal-Helge Haugen--the literary composer]. PMID- 1738279 TI - Age-related changes in oral sensation. AB - Oral sensation (including two-point discrimination, oral stereognosis, vibrotactile detection, somesthetic sensitivity, proprioception, and thermal sensitivity) was studied in 60 healthy adults in five age categories: 20 to 34, 35 to 49, 50 to 64, 65 to 79, and 80 years and above. Thermal and somesthetic sensitivity as well as proprioception did not change with age. Ability to differentiate tactile and vibratory sensation on the lip decreased after age 80 (P less than .01), but vibration detection on the soft palate did not change. Stereognostic ability remained good up to age 80, and then declined for four of the nine shapes tested (P less than .01). Two-point discrimination deteriorated on the upper lip (P less than .01), on the cheeks (P less than .02), and on the lower lip (P less than .06). Two-point discrimination on the tongue and palate did not change. It was noted that oral sensation remained good with aging, showing only a slight decline in function after age 80. PMID- 1738280 TI - The relationship between the nasal cycle and mucociliary clearance. AB - Nasal airway resistances were measured bilaterally on subjects at 30-minute intervals over 6 hours using anterior rhinomanometry. The first 10 subjects found to exhibit alternating congestion and decongestion of the nasal mucosa (i.e., the nasal cycle) were included in the study. Using the saccharin method, nasal mucociliary clearance was determined for each subject in both the congested and decongested phases of the cycle. The results were statistically significant at the P less than .09 level, highly suggestive of a difference in nasal mucociliary clearance between the two phases of the cycle, with the congested phase having the more rapid clearance. However, when compared to the mucociliary clearance times in disease states, the difference in transport times between the two phases is probably not clinically significant. PMID- 1738281 TI - Stapedectomy techniques in residency training. AB - The KTP-532 laser has decreased the technical difficulty involved in teaching and performing a stapedectomy in our residency program. Use of this laser has resulted in improved hearing and a decreased number of major and minor complications compared to an equal number of large fenestra stapedectomies performed with hand-held instruments. The major disadvantages of the KTP-532 laser are its cost and limited availability, and the inconvenience of a micromanipulator. The laser should not be relied upon entirely in performing a stapedotomy on a thick footplate. The University of Texas Medical Branch experience in training residents in both large and small fenestra stapedectomy is reported. PMID- 1738282 TI - Hearing preservation in acoustic neuroma surgery. AB - With advances in imaging, intracanalicular acoustic neuromas are identified readily in patients including, oftentimes, those with serviceable hearing. Fourteen patients were operated on in an attempt to preserve hearing. Hearing was retained in 10 (71%) of the 14. Serviceable hearing was present in 7 (50%), borderline serviceable hearing in 2 (14%), and nonserviceable hearing in 1 (7%). The problems, advantages, and disadvantages of the differing approaches are discussed. PMID- 1738283 TI - Temporal bone fractures: longitudinal or oblique? The case for oblique temporal bone fractures. AB - Classical descriptions and illustrations of temporal bone fractures are misleading. Both oblique and longitudinal fractures produce a similar fracture line in the middle cranial fossa; however, externally, they are different. Oblique fractures cross the petrotympanic fissure while longitudinal fractures run within it. In a study of 150 temporal bone fractures, the majority were oblique. An array of fracture planes accounts for most of the fractures observed. Depending on the direction of trauma, fracture planes rotate around an anteroposterior axis. When they approach the horizontal (axial) plane, they result in oblique fractures. True longitudinal fractures are rare. They are vertical and perpendicular to the oblique planes. PMID- 1738284 TI - The prevalence of migraine in Meniere's disease. AB - This study attempted to determine the prevalence of migraine in unilateral classic Meniere's disease and vestibular Meniere's disease. Diagnostic criteria for these three entities were identified and charts of patients with episodic vertigo were reviewed. A questionnaire was designed to assess the prevalence of migraine using criteria established previously by other authors. Questionnaires were mailed to patients with classic Meniere's disease, patients with vestibular Meniere's disease, and a normal control group. The response rates from the questionnaires in the three groups were 75%, 70%, and 36%. The percentages of the respondents who met the predetermined criteria for migraine in the three groups were 22%, 81%, and 33%. The significant difference in migraine prevalence between classic and vestibular Meniere's disease suggests the possibility of different etiologies for the two entities. PMID- 1738285 TI - Dysphonia in the aging: physiology versus disease. AB - A chart review from 151 dysphonic patients over the age of 60 was done to define aging related voice disorders. Overwhelmingly, patients suffered from dysphonia due to disease processes associated with aging rather than to physiologic aging alone. These include: 1. central neurological disorders affecting laryngeal function (e.g., stroke, Parkinson's disease, essential tremor, Alzheimer's disease); 2. benign vocal fold lesions (e.g., Reinke's edema, benign and dysplastic epithelial lesions); 3. inflammatory disorders (e.g., laryngitis sicca, medication effect); 4. laryngeal neoplasia; and 5. laryngeal paralysis. Typical laryngeal findings of vocal fold bowing and breathiness consistent with presbylarynges were present in only six patients. Presbylarynges is not a common disorder and should be a diagnosis of exclusion made only after careful medical and speech evaluation. PMID- 1738286 TI - Surgery for recurrent and residual cholesteatoma. AB - One hundred twelve patients (116 ears) were treated for recurrent and residual cholesteatoma. A retrospective review revealed that 66% had undergone canal wall down mastoidectomy at the previous surgery. The surgical procedure at revision was selected on the basis of an intraoperative assessment of the extent of disease, and clinical prediction of eustachian tube function. The average period of follow-up was 3.4 years. Revision surgery was successful in providing the patient with a safe, dry ear in 105 (91%) of 116 cases. Surgical principles and hearing results are presented. PMID- 1738287 TI - Early experience with percutaneous tracheotomy. AB - Early reports of a percutaneous dilatational technique for tracheotomy tube placement have been encouraging. This method uses a needle for placement into the trachea, a J-tipped guidewire, and progressively larger dilators to widen the stoma for insertion of a tracheotomy tube. A prospective study was undertaken to assess the efficacy of this percutaneous tracheotomy technique. Serious complications were encountered, including difficulty with dilatation, excessive bleeding, false passage of the tracheotomy tube, and death. Because of this unacceptable morbidity, the study was terminated after enrollment of only seven patients. Percutaneous tracheotomy is a dangerous procedure with potential for catastrophic complications. These complications were encountered by third- and fourth-year surgical residents performing the procedure under close supervision. If the puncture technique is further popularized and attempted by untrained physicians, these authors predict many disasters. PMID- 1738288 TI - Abductor laryngeal dystonia: a series treated with botulinum toxin. AB - Abductor laryngeal dystonia (LD) is characterized by a hoarse voice quality which is broken up by breathy or whispered portions. Botulinum toxin injection (Botox) has been a safe and effective treatment for adductor laryngeal dystonia and is currently accepted medical therapy. As an extension of the established treatment program, in 1989 treatment of abductor LD was initiated. Thirty-two patients have been treated by sequential percutaneous electromyogram-guided (EMG) injections of the posterior cricoarytenoid (PCA) muscles. Most patients required treatment of both PCA muscles and improved to an average of 70% of normal voice. Patients who had a preexisting tremor, evidence of dystonia in other muscle groups, vocal tremor, or respiratory dysrhythmia had less improvement. Ten patients also required injection of the cricothyroid muscles and/or type I laryngoplasty. PMID- 1738289 TI - Oncofetal antigen expression in head and neck carcinoma. AB - Oncofetal antigens (OFA) are proteins expressed during periods of embryonal/fetal development and on malignant cells. Previous investigations detected the presence of phase-specific 44- and 200-kd OFA, using a monoclonal antibody (MoAb 115). This study will determine if primary head and neck squamous cell carcinomas express the 44-kd OFA, and will assess the possible role of OFA in oncogenesis. Fifteen primary human head and neck squamous cell carcinomas (HNSCC) and six HNSCC cell lines were tested for OFA expression. Thirteen primary cancers and three cell lines demonstrated various degrees of OFA positivity. Oncofetal antigens are proposed to represent a proto-oncogene active during fetal development and malignant growth in head and neck squamous cell carcinomas. PMID- 1738290 TI - Influence of middle ear immune response on the immunological state and function of the inner ear. AB - According to clinical experience, a causative correlation between otitis media and sensorineural hearing loss is likely. During an otitis media, inflammatory mediators should be released and diffuse through the round window membrane to cause an immune response of the inner ear. Using 20 guinea pigs, an immunologically caused otitis media was induced. Auditory evoked potentials were registered by means of electrocochleography and electric response audiometry from day 0 to day 7. Each time, before and after starting the immune response serum, middle ear effusion and perilymph were sampled and the concentration of interleukin-2 (IL-2) analyzed. Decalcified temporal bones were examined immunohistochemically. In this study, IL-2 was found in the middle ear effusion and perilymph, and there was evidence of an immune response of the inner ear during an otitis media. Histological results were in close correlation with this event. Electrophysiological data showed conduction deafness and signs of sensorineural hearing loss with a maximum at day 3. PMID- 1738291 TI - Spontaneous and evoked otoacoustic emissions in preterm neonates. AB - Spontaneous (SOEs) and evoked otoacoustic emissions (EOEs) were recorded in a group of preterm neonates (N = 134 ears) in order to study the basic properties of SOEs and EOEs as a function of gestational age. In the study, it was found that: 1. EOEs were recorded in 93% of the tested ears; 2. SOEs were recorded in 61% of the tested ears; 3. there were no statistically significant variations of EOE amplitude with gestational age; 4. EOE spectrum did not vary with age; and 5. the two main factors influencing EOE amplitude were the SOE presence and the fast Fourier transform spectrum, especially the lower limit of the spectrum. Thus, the maturation of outer hair cell properties appears to be complete at 32 weeks of gestational age. Because a number of infants at risk for hearing loss are preterm babies, screening for EOEs, an objective, rapid, and nontraumatic technique, may prove useful in evaluating peripheral auditory dysfunction in preterm neonates. PMID- 1738292 TI - Compound action potentials recorded from the exposed eighth nerve in patients with intractable tinnitus. AB - Compound action potentials (CAP) were recorded directly from the exposed intracranial portion of the eighth nerve in 19 patients undergoing microvascular decompression (MVD) of the eighth nerve for intractable tinnitus. The waveform of the CAPs recorded in patients with tinnitus varied from normal to highly abnormal, but only in 1 patient were there distinct abnormalities in the waveform of the CAP that could not be attributed to the patient's hearing loss. The mean values of the latencies of the N1 and N2 peaks in the CAPs recorded from the exposed eighth nerve in patients with tinnitus and high-frequency hearing loss were virtually indistinguishable from the latencies obtained in patients with similar hearing loss but no tinnitus. There was no statistically significant difference between the latency of peak III in the brainstem auditory evoked potentials (BAEPs) in these two groups of patients, but the latency of peak V was slightly shorter (statistically significant) in the patients with tinnitus than it was in the patients without tinnitus. PMID- 1738293 TI - Endoscopic pituitary tumor surgery. PMID- 1738294 TI - Maxillary removal and reinsertion for improved access to anterior cranial base tumors. AB - Portions or all of the maxillae are oftentimes removed solely to provide access to certain cranial base tumors rather than because they are involved directly with disease. The purpose of this report is to describe an approach that involves removal of one or both maxillae to improve tumor exposure with subsequent reinsertion as free bone grafts which are stabilized with titanium craniofacial fixation plates. The titanium permits postoperative imaging studies and radiotherapy. Eleven patients ranging from 10 to 69 years of age have undergone 12 operations using this technique for resection of 4 benign and 8 malignant tumors at The Ohio State University. Seven of the 8 patients with malignancies underwent postoperative radiation therapy. There have been no permanent complications and no evidence of bone resorption in this group after follow-up of up to 15 months. PMID- 1738295 TI - Additional exposure during translabyrinthine surgery. PMID- 1738296 TI - Endothelin-1- and endothelin-3-induced vasorelaxation via common generation of endothelium-derived nitric oxide. AB - The vasorelaxant effects by endothelin-1 (ET-1) and endothelin-3 (ET-3), and their mechanisms of action were studied in isolated porcine pulmonary arterial strips. ET-1 and ET-3 dose-dependently (10(-9) - 10(-8) M) relaxed vascular strips precontracted with norepinephrine only in the presence of endothelium. The maximal vasorelaxant effect by ET-1 was about 70% of that by ET-3. The ET-1- and ET-3- induced vasorelaxation was blocked by NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The present data suggest that vascular smooth muscle relaxation induced by ET-1 and ET-3 is mainly ascribed to synthesis and release of nitric oxide from L-arginine in endothelium. PMID- 1738297 TI - Prediction of tertiary structures in 'scorpion-toxin' type proteins. AB - In the three-dimensional architecture of macromolecules, the structural stability and proper folding manifest due to cooperative packing interaction of various segments. Hydrophobicity is the major factor stabilizing protein-protein associations. In the disulfide-containing proteins, S-S bonds are integral part of structural motifs and large part of the protein-folding problem can be reduced to identifying and understanding motifs and subdomains of these proteins. Identifying such a motif with S-S bonds in 'scorpion-toxin' type proteins, and from model-building studies, five tertiary structural models for these type of proteins can be proposed. These canonical structural models can be refined by regular minimum energy and computer simulation methods to arrive at the final tertiary structures. Such 'models' can be of considerable use i) in understanding the biochemical reaction mechanisms in the structure-function relationships, ii) structure determination by X-ray methods (molecular replacement method), iii) drug design etc. PMID- 1738298 TI - Inhibitory effects of endothelin-1 and endothelin-3 on prolactin release: possible involvement of endogenous endothelin isopeptides in the rat anterior pituitary. AB - Spontaneous prolactin release from the isolated rat anterior pituitary was inhibited by endothelin-1 in a dose-dependent manner (10(-8)-10(-6) M). Endothelin-3 also inhibited spontaneous prolactin release with an almost identical dose-response relationship as endothelin-1. These inhibitory effects were unaffected by application of a dopamine D2-receptor antagonist, YM-09151-2 (10(-7) M). Rat anterior and posterior pituitary glands were abundant in both endothelin-1 and endothelin-3, as compared with other regions of the brain. The present results suggest that endogenous endothelin-1 and endothelin-3 in the anterior and posterior pituitary are involved in the inhibitory regulation of prolactin secretion as autocrine or paracrine factors. PMID- 1738299 TI - Prolonged increase of corticosterone secretion by chronic social stress does not necessarily impair immune functions. AB - The influence of a chronic social stress upon immunity was investigated in Wistar rats, submitted for four weeks to two different behavioral situations, balanced in a factorial design: housing with three females and membership rotation. The combination of these two factor led to adrenal enlargement (43.3%), thymus involution (39.5%) and increased basal corticosterone levels, all indices of activation of the hypothalamic-hypophysis-adrenal axis. However, neither natural killer cell activity, splenocyte reactivity to mitogen nor the rate of spontaneous development of antibodies against Mycoplasma pulmonis, a common pathogen of the respiratory tract, were changed in the endocrine activated animals. Analysis of the data on kinetics of stress at 1, 7 and 28 days after the initial mixing of the animals gave the same results. These data question the immunosuppressant activity usually conferred to corticosteroids, at least when adrenal hyperactivity is induced by chronic environmental stressors. PMID- 1738300 TI - Secretory cholinesterase of Ancylostoma ceylanicum: effect of tubulin binding agents and benzimidazole anthelmintics. AB - Ancylostoma ceylanicum, the human hookworm parasite, exhibited significant secretion of cholinesterase when maintained in vitro in RPMI-1640 medium. Secretion of the enzyme was linear up-to 4 hours of incubation. About 40 percent of the total cholinesterase activity was localized in the soluble fraction, while remaining activity was associated with the particulate fraction of the nematode. Exposure of the hookworms to colchicine in vitro caused significant inhibition in secretion of the enzyme by the parasite with concomitant accumulation of cholinesterase within the adult worms. Vinblastine did not show noticeable effect on the enzyme secretion as well as activity within the parasite. Incubation of hookworms with some benzimidazole anthelmintics viz., mebendazole or albendazole significantly reduced the capacity of the worms to secrete cholinesterase and increase in enzyme activity within the parasite. Adult worms recovered from mebendazole treated hamsters exhibited about 3 fold greater activity of cholinesterase as well as significantly lower capacity to secrete cholinesterase in vitro as compared to the worms recovered from untreated animals. These observations indicate role of microtubules in the secretion of cholinesterase by hookworms and as a target for the action of benzimidazole anthelmintics. PMID- 1738301 TI - Criminal penalties for maternal substance abuse. PMID- 1738302 TI - Helping families say good-bye. PMID- 1738303 TI - Unit-based family-support groups: a reminder. PMID- 1738304 TI - Communicating with addicted women in labor. PMID- 1738305 TI - Infant cardiopulmonary resuscitation for expectant and new parents. PMID- 1738306 TI - Teaching parents infant CPR--lecture or audiovisual tape? PMID- 1738307 TI - Shoulder dystocia: when to use suprapubic or fundal pressure. AB - "The delivery of the head with or without forceps may have been quite easy, but more commonly there has been a little difficulty in completing the extension of the head. The hairy scalp slides out with reluctance. When the forehead has appeared it is necessary to press back the perineum to deliver the face ... time passes. The child's head becomes suffused. It endeavors unsuccessfully to breathe. Abdominal efforts by the mother or by her attendants produce no advance; gentle head traction is equally unavailing. Usually equanimity forsakes the attendants. They push, they pull. Alarm increases. Eventually by greater strength of muscle or by some infernal juggle, the difficulty appears to be overcome, and the shoulders and trunk of a goodly child are delivered. The pallor of its body contrasts with the plum-colored cyanosis of the face, and the small quantity of freshly expelled meconium about the buttocks. It dawns upon the attendants that their anxiety was not ill-founded, the baby lies limp and voiceless, and too often remains so despite all efforts at resuscitation". PMID- 1738308 TI - The RU 486 story: the French experience. PMID- 1738309 TI - From failures to major learning experiences. PMID- 1738310 TI - Haemolysin-derived synthetic peptides with pore-forming and haemolytic activity. AB - Escherichia coli haemolysin (Hlya) is a pore-forming protein which belongs to the family of 'Repeat-toxins' (RTX) (Lo et al., 1987; Lally et al., 1989; Kraig et al., 1990). A model for the pore-forming structure of HlyA has been proposed (Ludwig et al., 1991) which consists of eight transmembrane segments all present in this hydrophobic region of HlyA. We report here that two synthetic peptides of 10 and 8 amino acids in length (Pep1 and Pep2, respectively), which are derived from transmembrane segment V, are able to form pores in an artificial lipid bilayer. In addition, Pep1 exhibits strong haemolytic activity when tested on human red blood cells (HRBCs). The haemolytic activity of Pep1 and of E. coli haemolysin is completely inhibited by antibodies raised against Pep1. PMID- 1738311 TI - Bacillus subtilis chemotaxis: a deviation from the Escherichia coli paradigm. AB - In Escherichia coli, chemotactic sensory transduction is believed to involve phosphoryl transfer for excitation, and changes in receptor methylation for adaptation. In Bacillus subtilis, changes in degree of receptor methylation do not bring about adaptation. Novel methylation reactions are believed to be involved in excitation in B. subtilis. The main chemotaxis proteins of E. coli- CheA, CheB, CheR, CheW and CheY--are present in B. subtilis but play somewhat different roles in the two organisms. Several unique chemotaxis proteins are also present in B. subtilis. Some of the properties of B. subtilis chemotaxis are also seen in Halobacterium halobium, suggesting that there may be a similar underlying mechanism that predates the evolutionary separation of the bacteria from the archaea and eucarya. PMID- 1738312 TI - On the evolution of functional secondary metabolites (natural products). AB - It is argued that organisms have evolved the ability to biosynthesize secondary metabolites (natural products) because of the selectional advantages they obtain as a result of the functions of the compounds. The clustering together of antibiotic biosynthesis, regulation, and resistance genes implies that these genes have been selected as a group and that the antibiotics function in antagonistic capacities in nature. Pleiotropic switching, the simultaneous expression of sporulation and antibiotic biosynthesis genes, is interpreted in terms of the defence roles of antibiotics. We suggest a general mechanism for the evolution of secondary metabolite biosynthesis pathways, and argue against the hypothesis that modern antibiotics had prebiotic effector functions, on the basis that it does not account for modern biosynthetic pathways. PMID- 1738313 TI - spbA locus ensures the segregational stability of pTH1030, a novel type of gram positive replicon. AB - The replication region of the plasmid pHT1030 of Bacillus thuringiensis was previously mapped to a 2.9 kb DNA fragment. The DNA sequence was analysed and it was shown that the minimal replicon resides within a 1 kb fragment of DNA carrying no potential protein coding sequence. Moreover, no production of single stranded DNA intermediates was detected in the plasmid-containing cells. pHT1030 therefore belongs to a class of replicons not previously described in Gram positive bacteria. Examination of the segregational stability of deletion derivatives of pHT1030 in bacilli defined two stability regions. One is located within the minimal replicon of pHT1030, whereas the second (spbA) is not required for replication. spbA encodes a 15 kDa protein and ensures the segregational stability of the plasmid. This effect of spbA is particularly highlighted in sporulation. The absence of the spbA locus gives rise to plasmid-free spores at high frequency, whereas the spbA+ plasmids are stably maintained. The stability of the plasmids during sporulation seems to be correlated with an unequal division of the cell by the sporulation septum. PMID- 1738314 TI - Membrane topology of the integral membrane components, OppB and OppC, of the oligopeptide permease of Salmonella typhimurium. AB - The oligopeptide permease of Salmonella typhimurium is a periplasmic binding protein-dependent transport system. Five gene products, OppABCDF, are required for the functioning of this transporter, two of which (OppB and OppC) are highly hydrophobic, integral membrane proteins and are responsible for mediating passage of peptides across the cytoplasmic membrane. OppB and OppC are each predicted, from their sequences, to span the membrane many times. In this paper we describe experimental evidence confirming these predictions using a combination of biochemical, immunological and genetic procedures. Each of these two proteins is shown to span the membrane six times, with the N- and C-termini both being located at the cytoplasmic face of the membrane. Opp is apparently a typical member of the ABC (ATP-binding cassette) superfamily of transporters. These findings, therefore, have general implications for the organization and function of other ABC transporters, including the human multidrug resistance protein and the product of the cystic fibrosis gene. PMID- 1738315 TI - Pseudomonas aeruginosa AlgB, which modulates the expression of alginate, is a member of the NtrC subclass of prokaryotic regulators. AB - The Pseudomonas aeruginosa exopolysaccharide alginate is an important virulence factor in chronic pulmonary infections of cystic fibrosis patients. We determined the nucleotide sequence of the gene, algB, which regulates the level of exopolysaccharide produced by mucoid P. aeruginosa. The predicted amino acid sequence of AlgB revealed a high degree of similarity to the regulatory proteins in the NtrC subclass of 'two-component regulatory systems'. AlgB expression in Escherichia coli minicells showed a molecular weight of approximately 50,000 Da, comparable to that of the inferred amino acid sequence (49,318 Da). We show that algB is transcriptionally active in mucoid strains of P. aeruginosa and regulates the expression of the alginate biosynthetic gene, algD, thereby resulting in increased expression of alginate in mucoid P. aeruginosa. PMID- 1738316 TI - Isolation and characterization of sporulation-specific promoters in the yeast Saccharomyces cerevisiae. AB - A library of random yeast genomic DNA:lacZ fusions has been constructed using an episomal yeast-Escherichia coli shuttle vector (pCS1). Plasmid pCS1 requires insertion of a promoter and an in frame ATG codon upstream of its resident truncated lacZ gene to regulate expression in yeast. Yeast genomic DNA fragments of 4-6 kb were generated by partial digestion with Sau3A and ligated into the unique BamHI site of plasmid pCS1 to generate a library of 5 x 10(4) individual E. coli transformants. This library was screened to identify promoter-lacZ fusions that were expressed uniquely during sporulation. Of 342 yeast transformants that exhibited beta-galactosidase activity, two were found to express the lacZ gene in a sporulation-specific manner. This paper presents the characterization of two genomic yeast DNA fragments containing promoters that control lacZ expression during the sporulation process. Expression from the promoter present in plasmid pJC18 occurred from 11-21 hours into the sporulation process, while the promoter in plasmid pJC217 was active from 4-14 hours. Staining of nuclear DNA to correlate nuclear morphology with timing of gene expression showed when each of these promoters was active in terms of the morphological stages of sporulation. PMID- 1738317 TI - Pullulanase secretion in Escherichia coli K-12 requires a cytoplasmic protein and a putative polytopic cytoplasmic membrane protein. AB - The previously uncharacterized third and fourth genes (pulE and pulF) of the pullulanase secretion gene operon of Klebsiella oxytoca strain UNF5023 are, respectively, predicted to encode a 55 kDa polypeptide with a putative nucleotide binding site, and a highly hydrophobic 44 kDa polypeptide that probably spans the cytoplasmic membrane several times. Expression of pulE in minicells or under the control of a strong bacteriophage T7 promoter resulted in the production of a c. 58 kDa cytoplasmic protein. A representative PulE-beta-galactosidase hybrid protein created by Tnlac mutagenesis was also found mainly in the cytoplasm. These results are in line with the predicted absence from PulE of a region of sufficient hydrophobicity to function as a signal sequence. The PulF polypeptide could not be detected either in minicells or when the gene was transcribed from the T7 promoter, but the acquirement of three pulF-lacZ gene fusions that encoded hybrid proteins with relatively high levels of beta-galactosidase activity indicates that this gene can be transcribed and translated. Gene disruption experiments indicated that both pulE and pulF are required for pullulanase secretion in Escherichia coli K-12. Both proteins exhibit considerable homology throughout their entire lengths with other proteins involved in protein secretion, pilin assembly, conjugation and transformation competence in a variety of bacteria. In addition, PulE protein has consensus sequences found in a wide variety of nucleotide-binding proteins. This study completes the initial characterization of the pullulanase secretion gene operon, which comprises 13 genes that are all essential for the transport of pullulanase across the outer membrane. PMID- 1738318 TI - Child injury prevention. PMID- 1738319 TI - Metastatic liver cancer: no cause for nihilism. PMID- 1738320 TI - Tuberculosis in Australia--a forgotten disease. PMID- 1738321 TI - Childhood pedestrian injuries in the Perth metropolitan area. AB - OBJECTIVE: To examine the characteristics of childhood pedestrian injuries in the Perth metropolitan area from 1980 to 1989. DESIGN: Retrospective descriptive study. SETTING: Perth metropolitan area, Western Australia. PARTICIPANTS: Child pedestrians aged 0 to 14 years who were injured during the period 1 January 1980 to 31 December 1989. MAIN OUTCOME MEASURES: An extensive database which reported fatal and non-fatal motor vehicle collisions was used to obtain details on the child pedestrian, the vehicle involved in the collision, and the environmental factors related to these injuries. RESULTS: A total of 1282 child pedestrian injuries were reported in the 10 year period. Children aged between 5 and 9 years, and were overrepresented among those injured. This study also demonstrated a similar proportion of injuries involving the 10-14 year age group. Injuries frequently occurred mid block, on local urban roads, between the hours of 3 p.m. and 7 p.m., and a greater than expected proportion of drivers involved in these collisions were in the under-21 age category. To describe the pattern of childhood pedestrian injuries we calculated both age-specific injury rates, and injury rates based on the number of registered motor vehicles. The latter revealed a greater than 20-fold variation between local government areas. CONCLUSIONS: Further analytical research, incorporating a measure of the child pedestrian's exposure to roads and traffic is required to identify those features in the individual and the environment which have a significant influence on the likelihood of a collision. Such research is required to institute effective preventive measures. PMID- 1738322 TI - Childhood poisoning--a changing profile with scope for prevention. AB - OBJECTIVES: To study the pattern of poisoning in children admitted to the Children's Hospital between 1983 and 1988; to compare this pattern with the last study of poisoning in childhood from this institution, done in 1956; and to survey knowledge of a sample of general practitioners and pharmacists about common childhood poisonings. DESIGN: A retrospective review of 407 medical records of children admitted after poisoning and a postal questionnaire to 150 randomly selected pharmacists and 150 randomly selected general practitioners. RESULTS: Poisoning accounted for one in 200 admissions to the Children's Hospital. The pattern of poisoning has changed since 1956 when the main agents were kerosene, pesticides, aspirin and digoxin. Now they are the benzodiazepines, iron preparations, paracetamol and anticonvulsants. There were four deaths due to the ingestion of quinine, caustic soda, ferrous sulphate and an arsenic-based weed killer respectively. Five per cent of the admissions resulted in significant morbidity. Sixty-five per cent of general practitioners and 45% of pharmacists responded to the questionnaire. The high toxicity of quinine, anticonvulsants, iron preparations and digoxin was not widely appreciated by over 50% of the general practitioners while over 60% of the pharmacists were not aware of the high toxicity of anticonvulsants and paracetamol. CONCLUSIONS: Although the pattern of childhood poisoning has changed, it remains a significant but largely preventable cause of mortality and morbidity. PMID- 1738323 TI - Survey of neonatal meningitis in Australia: 1987-1989. AB - OBJECTIVE: To identify incidence, bacterial aetiology, outcome after treatment and risk factors for poor outcome of neonatal meningitis. DESIGN: Retrospective survey of neonatal meningitis occurring in Australia between January 1987 and December 1989. Data were obtained from Medical Records and Microbiology Departments of hospitals with neonatal nurseries. SETTING: Neonatal nurseries throughout Australia. PATIENTS: 116 infants under 6 weeks of age with bacterial or fungal meningitis. RESULTS: The minimum incidence was 0.17 per 1000 live births. Traditional neonatal pathogens were responsible for 60% of cases (group B streptococci, 35%; Escherichia coli, 22%), childhood meningeal pathogens for 10% and opportunistic pathogens for 30%. Risk factors for meningitis, including prematurity, were more common among those with meningitis due to E. coli or opportunistic pathogens than among those with infections due to group B streptococci, Listeria monocytogenes or the childhood pathogens (46/60 v. 11/55; P less than 0.0001). Meningitis was more likely to be due to Gram-negative bacteria in premature infants (less than 36 weeks gestation) than in full-term infants (19/30 v. 20/86; P = 0.0002). The mortality overall was 26% but was higher in extremely premature infants (less than 29 weeks) (6/9 v. 24/107; P = 0.009) and among 13 patients who were judged to have had inappropriate initial therapy (7/13 v. 21/97; P = 0.04). Long-term sequelae occurred in at least 23% of survivors, but were more common in those with Gram-negative meningitis (6/10 v. 13/76; P = 0.012). CONCLUSIONS: Initial therapy with penicillin or amoxycillin plus cefotaxime is appropriate for most infants with bacterial meningitis. Since some less common Gram-negative bacteria isolated in this survey were resistant to cefotaxime, an aminoglycoside should be added, initially, in Gram-negative meningitis. PMID- 1738324 TI - Climatic temperature and variation in the incidence of sudden infant death syndrome between the Australian states. AB - OBJECTIVE: To describe the relationship between climatic temperature and the incidence of sudden infant death syndrome (SIDS) for the Australian States and examine the extent to which differences in climatic temperature might explain the regional variation of SIDS in Australia. DESIGN: Case series study. A generalised linear model was used to model the association between monthly average temperature and the incidence of SIDS. SETTING: The report is population based. Data are available from all Australian States. SUBJECTS: Cases of SIDS from birth to less than 12 months of age occurring in Queensland (1981-1987), New South Wales (1981-1987), Victoria (1984-1987), Tasmania (1975-1989), South Australia (1980-1989), and Western Australia (1980-1988). RESULTS: Every one degree Celsius decrease in average monthly temperature within the range 9 degrees C to 25 degrees C is associated with a 10.6% (95% confidence interval, 9.6%-11.7%) increase in the incidence of SIDS. Climatic temperature accounts for 84% of the interstate variation in the rate of SIDS. After controlling for the effect of temperature, a significant overall difference in SIDS incidence remains (P less than 0.0001) for the Australian States. CONCLUSION: Climatic temperature accounts for most but not all of the regional variation of SIDS incidence in the Australian States. The remaining variation may reflect differences in the maternal and infant characteristics of the State populations. PMID- 1738325 TI - Sudden infant death syndrome: factors contributing to the difference in incidence between Victoria and Tasmania. AB - OBJECTIVE: To examine how much of the difference in incidence of sudden infant death syndrome (SIDS) between Tasmania and Victoria could be accounted for by the effect of differing climatic temperature and the effect of the differing prevalence of maternal and infant characteristics in the two State populations. DESIGN: A two population ecological comparison. Two previously published predictive models were applied to quantify the contribution of several factors to the higher incidence of SIDS in Tasmania compared with Victoria. SETTING: A population based study involving the two Australian States of Tasmania and Victoria. PATIENTS: The characteristics of the 1985 to 1987 live birth cohorts of Tasmania and Victoria were examined. Cases were defined as all infants dying in 1985 to 1987 whose cause of death was stated as SIDS. RESULTS: The rate of SIDS for Tasmania and Victoria 1985 to 1987 was 3.76 per 1000 live births and 2.18 per 1000 live births respectively. Adjustment of the Tasmanian rate for the effect of the interstate difference in climatic temperature resulted in a lower Tasmanian rate of 2.92 per 1000 live births. Adjustment for the effect of interstate differences in maternal age, birthweight, infant sex, month of birth and intention to breast-feed at hospital discharge decreased the Tasmanian rate to 2.47 per 1000 live births. CONCLUSION: Approximately 82% of the interstate difference in SIDS incidence between Tasmania and Victoria from 1985 to 1987 can be accounted for by differences in climatic temperature, maternal age, birth weight, infant sex, month of birth and feeding intention at hospital discharge. PMID- 1738326 TI - General practice. Research in general practice. Establishing a rural research network. PMID- 1738327 TI - Teaching the students. Teaching communication skills in small groups. PMID- 1738328 TI - Diagnosis and treatment of confirmed and suspected snake bite. Implications from an analysis of 46 paediatric cases. AB - OBJECTIVE: To identify reliable predictors of envenomation in suspected snake bite and to examine the current standard of treatment in envenomed patients. DESIGN: Retrospective cohort analysis of children presenting with suspected or confirmed snake bite in southern mainland Australia. Detection of snake venom in urine or blood was taken as proof of envenomation. SETTING: Intensive Care Unit, Royal Children's Hospital, Melbourne. PATIENTS: Forty-six children presenting between 1979 and 1990. MAIN OUTCOME MEASURES: Positive and negative clinical evidence, venom tests, and coagulation tests. RESULTS: Twenty-seven children (59%) had suspected bites; 10 (22%) were bitten but not envenomed; 9 (19%) were envenomed. Two died of coagulopathy. Headache, abdominal pain or vomiting were moderately predictive of envenomation (positive predictive values of 63%, 57% and 64% respectively). Coagulopathy was a highly sensitive, specific and reliably predictive (100%) indicator of envenomation. The pressure-immobilisation bandage was used in 28% of cases at the scene of the bite and in 41% on contact with medical or paramedical services. Twelve patients received antivenom; of these, six received adrenaline as premedication. CONCLUSION: Headache, abdominal pain, nausea or vomiting, or abnormal coagulation tests accurately predict envenomation by snakes in southern mainland Australia. More or better education on first aid and clinical management of snake bite is needed. PMID- 1738329 TI - Analgesia for day surgery. AB - OBJECTIVE: To review current and potential analgesic techniques in day surgery, with particular regard to their pharmacology. DATA SOURCES: Recent articles on analgesia for surgery and day surgery were retrieved from Index Medicus for 1988 1990. Pharmacokinetic data were collated from recent textbooks and articles. DATA SYNTHESIS: The reviewed information is integrated with a pharmacological approach and personal experience with the use of postoperative analgesia. CONCLUSIONS: Combination analgesia therapy is the best approach for postoperative analgesia for day surgery. The usefulness of preoperative blockade of the pain sensation which limits activation of the central pain pathway and decreases analgesic requirements, is also emphasised. Examples of measures for relief of mild, moderate and severe pain are given. PMID- 1738330 TI - Augmentin-induced jaundice with a fatal outcome. AB - OBJECTIVE: To report a case of death due to Augmentin-induced cholestatic hepatitis and discuss a possible drug interaction between Augmentin and oestrogenic steroids. CLINICAL FEATURES, INTERVENTION AND OUTCOME: An 81-year-old man, on oestrogen therapy for prostatic malignancy, presented with obstructive jaundice one week after completing a four-week course of Augmentin for recurrent urinary tract infection. Liver biopsy showed features of a drug-induced cholestatic hepatitis with bile duct injury. His clinical course was marked by progressive deterioration with increasing jaundice and the development of hepatic encephalopathy. A course of prednisolone did not result in any improvement and he died nine weeks after the onset of jaundice. CONCLUSIONS: The cholestatic hepatitis induced by Augmentin is usually reversible but may be progressive, leading to death. The concurrent administration of ethinyloestradiol, a potentially cholestatic agent, may have altered the susceptibility and/or course of the reaction in this patient. PMID- 1738331 TI - Mycobacterium bovis (BCG) vaccination. Progressive disease in a patient asymptomatically infected with the human immunodeficiency virus. AB - OBJECTIVE: To report a case of progressive disease caused by Mycobacterium bovis after BCG vaccination in a patient asymptomatically infected with the human immunodeficiency virus (HIV). CLINICAL FEATURES: A 34-year-old white man about to commence employment as a developmental care worker had a BCG vaccination. Five months later, he had a positive result to a serological test for HIV antibody. Nine months after BCG vaccination, he presented with fever (38.7 degrees C), a large left axillary lymph node and a small left pleural effusion. The lymph node was biopsied and acid-fast bacilli observed in Ziehl-Neelsen stained smears. Culture grew Mycobacterium bovis (BCG). TREATMENT AND OUTCOME: He was successfully treated with isoniazid, rifampicin and ethambutol for a period of nine months. CONCLUSION: BCG vaccination of asymptomatic HIV-positive patients is not recommended. The detection of those at risk for HIV infection before vaccination administration is essential. Self-exclusion based on information supplied to all potential recipients is likely to be the most effective method. PMID- 1738332 TI - An epidemiological study of snake bite envenomation in Papua New Guinea. PMID- 1738333 TI - Can infant death from child abuse be prevented? PMID- 1738334 TI - Teaching medical students about violence. PMID- 1738335 TI - Acute psychosis after withdrawal of vigabatrin. PMID- 1738336 TI - Cholestasis with ticarcillin-potassium clavulanate (Timentin) PMID- 1738337 TI - General practitioner databases in Australia. PMID- 1738338 TI - Karitane Mothercraft Society. PMID- 1738339 TI - Lead: subtle forms and new modes of poisoning. PMID- 1738341 TI - Defibrillators on Qantas aircraft. PMID- 1738340 TI - Treatment of recurrent staphylococcal furunculosis. PMID- 1738342 TI - The battle of the couches and the rats. PMID- 1738343 TI - Psychotherapy: from Freud to cognitive science. PMID- 1738344 TI - Quadrivalent meningococcal vaccine for use after splenectomy. PMID- 1738345 TI - The battle of the couches and the rats. PMID- 1738346 TI - Increasing the numbers of general practitioners who provide smoking cessation advice. PMID- 1738347 TI - Information provided in Australia about the size of standard drinks. PMID- 1738348 TI - Cardiac risk factor management. PMID- 1738349 TI - Haemopoietic toxicity and low-dose methotrexate. PMID- 1738350 TI - Inflammatory terminology. PMID- 1738351 TI - Geriatric suicide. PMID- 1738352 TI - Geriatric suicide. PMID- 1738353 TI - Has the Missouri State Board of Registration for the Healing Arts gone too far? PMID- 1738354 TI - Bronchopulmonary lavage for pulmonary alveolar proteinosis. AB - In summary, total-lung bronchopulmonary lavage was performed five times on two patients under general anesthesia with controlled ventilation using a Robert-Shaw double lumen ETT. One lavage was complicated by a hydrothorax that was treated without untoward sequelae. No significant hypoxemia, circulatory impairment or leakage of lavaged fluid into the opposite lung was noted on any occasion. The average time of all procedures was 108 minutes (range 80-150 minutes), and patients were extubated on all occasions 2 to 5 hours after the treatment. Patients were discharged 24 to 36 hours after the last lavage with improvement, though not resolution, of the alveolar infiltrates radiographically. The ABG analysis revealed minimal improvement in oxygenation in Case No.1 from a preoperative paO2 of 60 mmHg on room air to a paO2 of 74 mmHg on the day of discharge. However, the patient was able to resume his normal activity level. In Case No.2, the patient's resting paO2 did not improve significantly from the preoperative value of 82 mmHg. Subjectively, however, the patient noted marked improvement. Prior to bronchopulmonary lavage, this patient's SaO2 decreased from 97% to 81% after walking 800 feet. Approximately a week and a half after discharge, the patient reported being able to run without symptoms and generally was feeling well. With careful attention to detail and the coordination of resources from the departments of anesthesia, pulmonary medicine, respiratory therapy and nursing services, bronchopulmonary lavage can be performed safely and efficiently in order to curtail the progressive hypoxemia which often develops in patients with PAP. PMID- 1738355 TI - Massive gastric hemorrhage due to small vessel erosion (the Dieulafoy lesion). PMID- 1738356 TI - Racial differences in cardiovascular disease mortality and risk factors. PMID- 1738357 TI - Advance directives: beginning the process. PMID- 1738358 TI - Outbreak of influenza A in a nursing home--New York, December 1991-January 1992. AB - During December 1991 and January 1992, an outbreak of influenza A occurred among residents of a nursing home in New York. From mid-October through mid-November 1991, influenza vaccine was administered to 295 (88%) of the 337 residents of the nursing home. The residents shared common dining and recreational areas; the mean age of residents was 83 years (range: 51-103 years); 256 (76%) were female. The prevalence of underlying illness in vaccinated and unvaccinated patients was not determined. PMID- 1738359 TI - Viscerotropic leishmaniasis in persons returning from Operation Desert Storm- 1990-1991. AB - From November 1990 through December 1991, seven men among the approximately 500,000 military personnel from the United States who participated in Operation Desert Storm had leishmaniasis involving internal organs diagnosed at Walter Reed Army Medical Center. In at least five of the cases, the species of the infecting parasite was Leishmania tropica (previously known as L. tropica minor), a parasite more commonly associated with cutaneous than with visceral leishmaniasis. PMID- 1738360 TI - Cholera associated with an international airline flight, 1992. PMID- 1738361 TI - Childbearing and contraceptive-use plans among women at high risk for HIV infection--selected U.S. sites, 1989-1991. AB - From September 1990 through August 1991, 2655 (49%) of the 5457 women reported with acquired immunodeficiency syndrome (AIDS) in the United States had been injecting-drug users (IDUs), and 1136 (21%) had had sexual intercourse with men who were IDUs (1). During the same period, 413 (56%) of the 735 children (aged less than 13 years) reported with AIDS were born to mothers who were either IDUs (38%) or sex partners of IDUs (18%) (1). Even though messages and services regarding prevention of human immunodeficiency virus (HIV) infection and pregnancy planning for women at high risk for HIV infection should be tailored to their specific needs, information regarding pregnancy history, plans for childbearing, and contraceptive use among such women is limited. This report characterizes the childbearing and contraceptive-use plans of women at high risk for HIV infection interviewed during 1989-1991 in three settings--methadone maintenance programs, drug-free outpatient programs, and detention facilities--in Florida, New Jersey, New York, and Pennsylvania. PMID- 1738362 TI - NIOSH Alert: Preventing electrocutions during work with scaffolds near overhead power lines. PMID- 1738363 TI - Lactoferrin in the mouse uterus: analyses of the preimplantation period and regulation by ovarian steroids. AB - Uterine expression of lactoferrin (LF) during the preimplantation period and its regulation by the ovarian steroids estradiol (E2) and/or progesterone (P4) in ovariectomized adult mice were examined. Immunoblot detection of LF in uterine cell lysates demonstrated the presence of this protein from days 1-8 of pregnancy [day 1 (D1) = day of vaginal plug]. Immunoprecipitation of 35S pulse-labeled uterine proteins showed that the relative rate of LF synthesis was high on D1, but below the level of detection by D4. Immunolocalization of LF in uterine sections showed intense luminal and glandular epithelial staining on D1 and D2, and progressively decreased staining through D4. Immunoreactive protein was also detected in cells, primarily concentrated in the stroma. The relative number of these cells was greatest on D1 and decreased progressively to a low number by D4. These cells were morphologically similar to neutrophils, which are known to contain LF protein, but little or no LF mRNA. Northern blotting showed that uterine LF mRNA levels were very high on D1 and D2 of pregnancy and decreased to low, but detectable, levels by D4. In situ hybridization to uterine sections showed that LF mRNA was highly abundant only in glandular and luminal epithelial cells, and followed the same pattern as immunolocalization on D1-D4 in epithelial cells. These results document two sources of LF in the preimplantation mouse uterus: neutrophils and epithelial cells. The synthesis of LF in the uterus reflects the abundance of epithelial LF mRNA, which is high on the first 2 days of pregnancy. Neutrophils that contain LF are also abundant in the uterine stroma during this time. E2 and/or P4 regulation of uterine LF was examined. LF mRNA was rapidly induced by E2 in ovariectomized adult mice, and this mRNA was localized exclusively to epithelial cells. P4 had little effect on uterine LF mRNA levels, but antagonized the prolonged induction of this gene by E2. E2 induced the accumulation of immunoreactive LF in uterine epithelial cells and the appearance of numerous immunopositive neutrophils distributed throughout the uterine stroma. P4 also antagonized these effects. Thus, E2 regulates LF gene expression in uterine epithelial cells and causes the recruitment of neutrophils into the uterus. These results suggest that LF may play an important role in early pregnancy and that uterine LF gene expression is regulated by a balance between estrogen and P4. PMID- 1738364 TI - Induction of cytoskeletal gene expression by insulin. AB - Insulin has rapid pleiotropic effects on cellular metabolism. In certain cell types, insulin can cause morphological changes by inducing rearrangements of cytoskeletal components, but the regulation of cytoskeletal gene expression by insulin has not been previously described. In the present work insulin was found to rapidly, but transiently, increase transcription of the cytoskeletal beta actin and alpha-tubulin genes in rat H4IIE hepatoma cells. Insulin-induced transcription of beta-actin mRNA was evident within 5 min and was maximal by 10 15 min at 1000% above control levels. beta-Actin transcription was induced at insulin concentrations as low as 5 x 10(-12) M insulin and was maximal at 5 x 10( 9) M. Transcription of the alpha-tubulin gene was also rapidly stimulated by physiological concentrations of insulin, but only to 300-400% above basal levels. For both the beta-actin and alpha-tubulin genes, the induction of transcription was transient, with a return to basal levels by 60-120 min. Transcription of neither the skeletal or cardiac alpha-actin gene nor the beta-tubulin gene was altered by insulin administration. Messenger RNA levels for the beta-actin and alpha-tubulin genes increased, but to a lesser extent than transcription, since these mRNAs were abundant and stable before the transient induction of transcription. Inhibitors of protein synthesis, in the presence or absence of insulin, also acutely stimulated transcription of these genes. PMID- 1738365 TI - Hormone- and phorbol ester-activated protein kinase C isozymes mediate a reorganization of the actin cytoskeleton associated with prolactin secretion in GH4C1 cells. AB - TRH regulates PRL secretion and synthesis in GH4C1 rat pituitary cells. TRH responses are associated with activation of protein kinase C (PKC) isozymes and elevation of cytosolic calcium. To determine which PKC isozymes are involved in TRH-directed responses, we evaluated the effect of TRH on GH cell alpha-, beta-, delta-, and epsilon-PKC isozymes. Immunoblot analysis demonstrated that TRH caused rapid redistribution of all isozymes to a Triton X-100-insoluble (i.e. cytoskeletal) fraction. Corollary immunocytofluorescence studies demonstrated that redistributed PKCs accumulate in cell peripheries. Exocytosis involves reorganization of the cytoskeleton, therefore, each of the GH cell PKCs is appropriately located to phosphorylate proteins important for cytoskeleton organization. To determine the relative contributions of calcium and PKC signal transduction pathways in mediating TRH responses, the effects of potassium depolarization (which increases cytosolic calcium) and phorbol dibutyrate (which activates all PKC isozymes without increasing calcium) were compared. The data indicate that TRH-mediated reorganization of vinculin proceeds via a calcium mediated pathway, whereas fragmentation of actin filaments proceeds via a PKC dependent pathway. Selective down-modulation of epsilon-PKC with prolonged TRH treatment was used to demonstrate that epsilon-PKC is not necessary for certain TRH-stimulated biological responses. PMID- 1738366 TI - Comparison of the 90-kilodalton heat shock protein interaction with in vitro translated glucocorticoid and estrogen receptors. AB - The rat glucocorticoid receptor is a 795-amino acid protein with the hormone binding domain located in the C-terminal portion of the molecule. In the absence of hormone, this domain displays a protein inactivation activity that represses the nuclear localization, DNA binding, and transcriptional regulatory activities of the receptor. This inactivation activity, which appears to be mediated by the 90-kilodalton heat shock protein (HSP90), is stronger in the glucocorticoid receptor than the corresponding activity of the estrogen receptor hormone binding domain. In order to analyze these differences, we have directly compared in vitro translated glucocorticoid and estrogen receptors in terms of their interaction with HSP90 by a coimmunoprecipitation assay employing two monoclonal antibodies, AC88 and 8D3, which react with different regions of the HSP90 molecule. Intact forms of both the glucocorticoid receptor and the estrogen receptor coimmunoprecipitated with endogenous HSP90 in reticulocyte lysates, indicating that both receptors were capable of binding to HSP90 when translated in vitro. By assaying a series of receptor deletion mutants, we found that the sequences required for HSP90 binding mapped to a similar region within the hormone binding domain of both receptors. While the hormone binding domain was found to be the only structural requirement for HSP90 binding to the glucocorticoid receptor, additional sequences N-terminal to the hormone binding domain were shown to be required for HSP90 binding to the estrogen receptor. These results are consistent with a postulate that differences in the protein inactivation activities of the glucocorticoid and estrogen receptor hormone binding domains may be secondary to differences in the interactions of these domains with HSP90. PMID- 1738367 TI - Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. AB - We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves. PMID- 1738368 TI - The origin of nuclear receptor proteins: a single precursor distinct from other transcription factors. PMID- 1738369 TI - The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. AB - Previous work by our laboratory has described the presence and widespread distribution of a PRL-like immunoreactive protein in brain. The persistence of this PRL in brain after hypophysectomy provided substantial evidence that brain PRL represented the product of a synthetic pool separate from that of the anterior pituitary PRL. To pursue this concept of independent synthesis further, we sought to determine whether brain tissue expressed PRL mRNA. Although we were easily able to detect a single species of PRL mRNA in pituitary by Northern hybridization, we could not visualize message in hypothalamus or extrahypothalamic brain by this technique. Therefore, we performed the polymerase chain reaction on cDNAs from anterior pituitary, hypothalamus, discrete extrahypothalamic brain regions, and other tissues. Hypothalamus and extrahypothalamic brain parts, including the cerebellum, caudate, brain stem, amygdala, thalamus, cortex, and hippocampus, were all positive to varying degrees. Lung and liver were negative, and anterior pituitary was consistently positive. All positive tissues, including anterior pituitary, expressed two hybridization signals: the expected amplified product and another smaller one. The smaller amplified product is presumably the result of an alternatively spliced transcript that is missing part of the PRL gene. Hypophysectomized animals did not express PRL message in brain, but expression was restored in hypophysectomized animals treated with testosterone. Transcripts for Pit-1 (GHF 1), a transcription factor important in regulation of pituitary PRL, were not detected in hypothalamus or any of the extrahypothalamic brain parts. The finding of testosterone stimulation of brain PRL message and undetectable levels of Pit-1 (GHF-1) in hypothalamic and extrahypothalamic brain regions indicates that the transcriptional regulation of PRL in the brain is different from that in the anterior pituitary. PMID- 1738370 TI - Thyrotropin (TSH)-releasing hormone-responsive elements in the rat TSH beta gene have distinct biological and nuclear protein-binding properties. AB - Two TRH-responsive elements have been identified in the rat TSH beta gene by deletion/mutation analysis of the 5'-flanking region of the gene and transfection of TSH beta-luciferase constructs into the GH3 pituitary cell line. Biological responsiveness was confirmed by inserting synthetic oligonucleotides next to the heterologous viral thymidine kinase (tk) promoter in tk luciferase (tkLUC) constructs. Both DNA regions, termed TSH A (at -274 to -258 bp) and TSH C (-402 to -385 bp), have a high level of sequence similarity to binding sites for the POU domain pituitary transcription factor Pit-1/GHF-1. In transfection assays, the TSH A region had no basal enhancer activity, but did confer 3- to 6-fold TRH- and PMA-stimulated transcriptional responses to the tk promoter. The TSH C region conferred basal enhancer activity (3- to 10-fold above control tkLUC) as well as a 2- to 3-fold TRH or PMA response. Combinations of TSH A and TSH C elements conferred both enhancer activity and a TRH- or PMA-stimulated response, but more than two copies of the regions resulted in no further stimulatory effect. Both TSH beta gene regions bound to nuclear proteins from GH3 cells, as determined by gel retardation analysis. The TSH A region DNA formed three prominent DNA-protein complexes, ranging from slowly to rapidly migrating bands and with calculated affinities of 32, 0.5, and 208 nM, respectively. The TSH C region formed two major complexes, which corresponded on the basis of mobility to the most slowly and rapidly migrating complexes formed by TSH A, but with calculated affinities of 3.1 and 33 nM. TSH C also formed a rapidly migrating minor complex unique for this gene region. The more rapidly migrating complexes appeared to be specific to nuclear proteins from GH3 cells. Treatment of cells with TRH did not significantly alter the affinity of protein binding. Mutation of TSH A and TSH C DNA by T to G substitutions abolished the ability of the DNA to confer a TRH response and severely inhibited the ability of the DNA to bind to GH3 nuclear proteins. Thus, transcriptional regulation of the rat TSH beta gene by TRH is correlated with the ability of the two TRH-sensitive elements to bind nuclear proteins. The differences noted in basal enhancer activity or the degree of TRH responsiveness may be related to some unique proteins bound to each DNA or to the differences in affinity of binding of the proteins common to both elements. PMID- 1738371 TI - Transcriptional and posttranscriptional regulation of type 1 plasminogen activator inhibitor and tissue-type plasminogen activator gene expression in HTC rat hepatoma cells by glucocorticoids and cyclic nucleotides. AB - We have reported previously that incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone causes a 90% decrease in tissue-type plasminogen activator (tPA) activity secondary to a 4-fold increase in plasminogen activator inhibitor-1 (PAI-1) mRNA accumulation. Dexamethasone also induces a modest and transient increase in tPA mRNA. The cyclic nucleotide analog 8-bromo-cAMP (cA) causes a greater than 50-fold increase in PA activity, the result of a 90% decrease in PAI-1 and a sustained 2-fold increase in tPA mRNA accumulation. Dexamethasone and cA in combination cause a 150-fold increase in PA activity, the result of an 80% decrease in PAI-1 and a synergistic 15-fold increase in tPA mRNA. To determine the mechanism of this complex hormonal regulation, we have examined rates of synthesis and decay of PAI-1 and tPA mRNAs. Here we report that dexamethasone induces a 5-fold increase in PAI-1 gene transcription and does not significantly alter PAI-1 message decay; PAI-1 mRNA has a half-life of about 4 h in both untreated and dexamethasone-treated cells. In contrast, cA regulates PAI-1 mRNA by both decreasing the rate of PAI-1 gene transcription by 60% and accelerating the rate of PAI-1 message decay. Regulation of tPA by cA, both alone and in combination with dexamethasone, occurs primarily at the level of transcription. Dexamethasone and cA-induced tPA mRNA has a half life of 2.75 h; tPA mRNA degradation is significantly inhibited by either cycloheximide or actinomycin-D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738372 TI - Epinephrine inhibits lipoprotein lipase gene expression in rat adipocytes through multiple steps in posttranscriptional processing. AB - Previous studies have demonstrated that in vitro treatment of adipocytes with catecholamines results in a decrease in the activity of the enzyme lipoprotein lipase (LPL). To examine the mechanism of this effect, primary cultures of rat adipocytes were cultured in the presence of various concentrations of epinephrine (10(-9)-10(-5) M). Epinephrine yielded a dose-dependent decrease in LPL activity; heparin-releasable LPL activity was reduced to 66% of control values after exposure to 10(-5) M epinephrine for 2 h. However, there was no effect of epinephrine on LPL immunoreactive mass, as measured by enzyme-linked immunosorbent assay. When cells were pulse labeled with [35S]methionine, there was a rapid and dose-dependent decrease in immunoprecipitable LPL. In spite of the decrease in LPL translation, neither epinephrine nor other catecholamines altered the level of LPL mRNA or the rate of LPL transcription. To further examine LPL posttranslational processing, cells were pulse labeled with [35S]methionine in the absence of epinephrine and then chased with unlabeled methionine in the presence of epinephrine. Cells exposed to epinephrine during the chase demonstrated a decrease in LPL secretion into the medium as well as a decrease in LPL degradation. The addition of epinephrine during LPL posttranslational processing did not alter the sensitivity of the newly synthesized LPL protein to endo-beta-N-acetylglucosaminidase-H. Thus, epinephrine had multiple effects on adipocyte LPL. Although there was a rapid decrease in LPL synthesis that was not due to changes in LPL mRNA, the level of LPL protein was unchanged under these conditions due to a decrease in LPL degradation and secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738373 TI - Structural organization of the follicle-stimulating hormone receptor gene. AB - We have characterized a series of rat genomic clones that code for the FSH receptor (FSHR) gene and approximately 14.8 kilobases of DNA up-stream of the transcriptional start sites. Southern blot analysis indicated that there was only a single gene for the FSHR. Primer extension and S1 nuclease experiments revealed the presence of two major transcriptional start sites at positions -80 and -98 relative to the translational start site. Transient expression studies of a fusion gene containing 830 basepairs of DNA 5' to the translational start site linked to the reporter gene chloramphenicol acyltransferase have shown that this portion of the gene is capable of acting as a transcriptional promoter in rat Sertoli cells. The FSHR gene contained 10 exons and nine introns. The first nine exons encoded the extensive amino-terminal domain of the receptor, while the last exon encoded the transmembrane-spanning and cytoplasmic domains. A repeated motif similar to that observed in the leucine-rich glycoprotein family was delineated within exons 2-9. Comparison of the FSHR gene to the LH receptor gene revealed a number of striking similarities which clearly indicate that these receptors evolved through gene duplication. The ancestral gene for these receptors presumably arose from a series of tandem duplications of the leucine-rich motif, which when combined with the common ancestral gene of the G-protein-coupled receptor family led to the current gene structure of the glycoprotein hormone receptors. PMID- 1738374 TI - Chicken progesterone receptor is phosphorylated by a DNA-dependent protein kinase during in vitro transcription assays. AB - We have reported previously that chicken progesterone receptor (PR) is phosphorylated in vivo in response to progesterone administration. Three phosphorylation sites have been reported, two of which show increased phosphorylation in response to hormone and one which is phosphorylated only in response to hormone administration. We found previously that PR lacking the hormone-dependent phosphorylation is active in an in vitro transcription assay. Since the source of general transcription factors is a HeLa nuclear extract which contains many kinases, we have analyzed the receptor for phosphorylation during the in vitro transcription assay. We report here that the receptor is rapidly and efficiently phosphorylated on new sites, causing a change in receptor mobility on sodium dodecyl sulfate-gels. This phosphorylation is strictly dependent upon the presence of double stranded DNA. A DNA-activated protein kinase with similar properties has been isolated previously from HeLa cell nuclei. We find that phosphorylation of PR with this purified enzyme mimics the phosphorylation observed in the transcription assay. These data suggest that a previously undetected additional series of DNA-dependent phosphorylations may be required for activation of the PR. PMID- 1738375 TI - Gonadotrope-specific expression of the human follicle-stimulating hormone beta subunit gene in pituitaries of transgenic mice. AB - The molecular basis for the cell-specific and hormonal regulation of the pituitary gonadotropin beta-subunit genes is unknown. To identify the essential DNA regulatory elements of the human FSH beta (hFSH beta) gene, we introduced a 10-kilobase cloned fragment encompassing the gene into the germline of transgenic mice. We showed by a combination of Northern blot hybridization, RIA, and immunofluorescence histochemistry that the hFSH beta gene was expressed exclusively in mouse pituitary gonadotropes. Human FSH beta was actively secreted, presumably as an interspecies heterodimer, with mouse alpha-subunit, and no free hFSH beta was detected in serum. Male transgenic mice consistently had higher basal pituitary expression and secretion of hFSH beta than the female transgenic mice. Castration combined with testosterone replacement caused a marked reduction in hFSH beta gene expression in transgenic males, but had no effect on the pituitary levels of FSH in normal male mice. These experiments demonstrate that the essential DNA regulatory elements and gonadotrope transcription factors required for cell-specific expression of the FSH beta gene must be conserved between human and mouse. There appear to be important differences in the hormonal regulation of the gene between species, however. PMID- 1738376 TI - Nosocomial transmission of hepatitis B virus associated with the use of a spring loaded finger-stick device. AB - BACKGROUND AND METHODS: From June 1989 through March 1990, 26 patients, of whom 23 had diabetes, contracted acute hepatitis B virus (HBV) infection in a hospital in California. All 26 patients and one HBV carrier (also a diabetic) had been admitted to a single medical ward during the six months before the case patients became infected with HBV. To determine the source of the infection, we conducted a retrospective cohort study of the 72 patients with diabetes who had been admitted to the ward from January through December 1989 and a case-control study comparing the 3 nondiabetic patients who contracted hepatitis with 20 nondiabetic controls. RESULTS: The retrospective cohort study of all the patients with diabetes who were admitted to the ward during 1989 found that those who underwent capillary blood sampling by finger stick with a spring-loaded lancet device were more likely to contract HBV infection than those who did not have finger sticks (attack rate, 42 percent vs. 0 percent; P = 0.08). In addition, a dose-response relation was observed between the number of finger sticks received and the frequency of hepatitis B (P = 0.002). The case-control study found that all 3 of the nondiabetic patients who contracted hepatitis underwent finger-stick blood sampling with the device, as compared with none of the 20 nondiabetic controls (P = 0.0006). A review of nursing procedures indicated that the platform of the device was not routinely changed after each use; this finding suggested that contamination of the platform by HBV-infected blood was the mechanism of percutaneous transmission of HBV. CONCLUSIONS: Proper use of finger-stick devices as well as strict adherence to universal precautions to avoid contamination by blood are required to decrease the possibility of transmission of blood-borne pathogens among hospitalized patients. PMID- 1738377 TI - Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor. AB - BACKGROUND: Since 1985, donors of organs or tissues for transplantation in the United States have been screened for human immunodeficiency virus type 1 (HIV-1), and more than 60,000 organs and 1 million tissues have been transplanted. We describe a case of transmission of HIV-1 by transplantation of organs and tissues procured between the time the donor became infected and the appearance of antibodies. The donor was a 22-year-old man who died 32 hours after a gunshot wound; he had no known risk factors for HIV-1 infection and was seronegative. METHODS: We reviewed the processing and distribution of all the transplanted organs and tissues, reviewed the medical histories of the donor and HIV-1 infected recipients, tested stored donor lymphocytes for HIV-1 by viral culture and the polymerase chain reaction, and tested stored serum samples from four organ recipients for HIV-1 antigen and antibody. RESULTS: HIV-1 was detected in cultured lymphocytes from the donor. Of 58 tissues and organs obtained from the donor, 52 could be accounted for by the hospitals that received them. Of the 48 identified recipients, 41 were tested for HIV-1 antibody. All four recipients of organs and all three recipients of unprocessed fresh-frozen bone were infected with HIV-1. However, 34 recipients of other tissues--2 receiving corneas, 3 receiving lyophilized soft tissue, 25 receiving ethanol-treated bone, 3 receiving dura mater treated with gamma radiation, and 1 receiving marrow-evacuated, fresh frozen bone--tested negative for HIV-1 antibody. Despite immunosuppressive chemotherapy, HIV-1 antibody appeared between 26 and 54 days after transplantation in the three organ recipients who survived more than four weeks. CONCLUSIONS: Although rare, transmission of HIV-1 by seronegative organ and tissue donors can occur. Improvements in the methods used to screen donors for HIV-1, advances in techniques of virus inactivation, prompt reporting of HIV infection in recipients, and accurate accounting of distributed allografts would help to reduce further this already exceedingly low risk. PMID- 1738378 TI - The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. AB - BACKGROUND: Stroke is an important cause of death among blacks, and intracerebral and subarachnoid hemorrhages account for nearly half of all early deaths from stroke. The present study investigates whether blacks and whites differ in their risk of having either intracerebral or subarachnoid hemorrhage. METHODS: We reviewed the medical records, autopsy reports, and CT scans of all patients suspected of having had an intracerebral or subarachnoid hemorrhage during 1988 among the nearly 1.3 million people in the Greater Cincinnati metropolitan area. RESULTS: There were 221 cases of first spontaneous intracranial hemorrhage among 1,086,462 whites (159 intracerebral and 62 subarachnoid hemorrhages), and 45 cases among 171,718 blacks (27 intracerebral and 18 subarachnoid hemorrhages). Blacks had 2.1 times the risk of subarachnoid hemorrhage of whites (95 percent confidence interval, 1.3 to 3.6) and 1.4 times the risk of intracerebral hemorrhage (95 percent confidence interval, 0.9 to 2.1). In those under the age of 75, the risk of intracerebral hemorrhage among blacks was 2.3 times that of whites (95 percent confidence interval, 1.5 to 3.6), whereas the risk among blacks 75 or older was one fourth that of whites (95 percent confidence interval, 0.1 to 0.8). Deaths within 30 days of intracerebral or subarachnoid hemorrhage accounted for 1.9 years of life lost per 1000 blacks under 65 years of age, as compared with 0.5 year per 1000 whites. CONCLUSIONS: Young and middle-aged blacks have a substantially higher risk of subarachnoid or intracerebral hemorrhage than whites of similar age. These types of stroke are important causes of excess mortality among young and middle-aged blacks. PMID- 1738379 TI - Allopurinol in the treatment of American cutaneous leishmaniasis. AB - BACKGROUND: Pentavalent antimony, the generally accepted treatment for leishmaniasis, is given parenterally, and it is expensive and not readily available in developing countries. An inexpensive, orally administered compound would be a substantial advance in treatment. Previous studies in vitro have shown synergism between allopurinol and pentavalent antimony in tissue-culture systems. We designed this clinical study to determine whether synergism could be demonstrated in patients. METHODS: We performed a randomized, controlled study of the efficacy of allopurinol plus meglumine antimoniate (Glucantime), as compared with meglumine antimoniate alone, in patients with cutaneous leishmaniasis, who were recruited from a village in southeastern Colombia. In addition, those who declined injections were treated with allopurinol alone, and those who declined any treatment were considered controls. All the patients were followed for one year after the completion of treatment. Lesions that healed completely at three months and remained healed during follow-up were considered to be cured. RESULTS: The cure rate for patients treated with meglumine antimoniate was 36 percent; the addition of allopurinol increased the rate to 74 percent (P less than 0.001). Treatment with allopurinol alone yielded a cure rate of 80 percent (P less than 0.001). There were no cures among the untreated patients. There was no significant difference between the cure rate with allopurinol plus meglumine antimoniate and that with allopurinol alone. No major toxic effects were observed. CONCLUSIONS: For the treatment of American cutaneous leishmaniasis, the combination of allopurinol and meglumine antimoniate is significantly more effective than meglumine antimoniate alone, probably because of the efficacy of allopurinol alone, which appears to be as good as the combination. PMID- 1738380 TI - Surgical management of spastic diplegia in cerebral palsy. PMID- 1738381 TI - Bladder cancer--field versus clonal origin. PMID- 1738382 TI - The challenge of intracellular pathogens. PMID- 1738383 TI - Carotid endarterectomy. PMID- 1738384 TI - Carotid endarterectomy. PMID- 1738385 TI - Carotid endarterectomy. PMID- 1738386 TI - Carotid endarterectomy. PMID- 1738387 TI - Carotid endarterectomy. PMID- 1738388 TI - Skin cancer and HLA antigens. PMID- 1738389 TI - Skin cancer and HLA antigens. PMID- 1738390 TI - Alcohol in mother's milk. PMID- 1738391 TI - Alcohol in mother's milk. PMID- 1738392 TI - Pericarditis caused by a sewing needle. PMID- 1738393 TI - Insurance coverage for preventive immunizations in childhood. PMID- 1738394 TI - Changing the consent rules for Desert Storm. PMID- 1738395 TI - To end an epidemic. Lessons from the history of diphtheria. PMID- 1738396 TI - Uremic pruritus: a review. PMID- 1738397 TI - Hypoglycemia with hyperinsulinemia in a chronic hemodialysis patient following parathyroidectomy. AB - We report a chronic hemodialysis patient with severe hyperparathyroidism who developed hypoglycemia with inappropriate hyperinsulinemia following parathyroidectomy. An abrupt fall in parathyroid hormone level and administration of large amounts of calcitriol may have resulted in increased insulin release and enhanced tissue sensitivity to insulin producing sustained hypoglycemia in this patient. PMID- 1738398 TI - Acute decline in renal function as a consequence of ovarian hyperstimulation syndrome. AB - Two cases of severe ovarian hyperstimulation syndrome following ovulation induction are described, one of them following in vitro fertilization and embryo transfer, and the other after conventional ovarian stimulation. This condition was associated with an acute reversible decline in renal function. The treatment and the possible pathophysiological mechanisms are discussed. PMID- 1738399 TI - Renal insufficiency due to bilateral primary renal lymphoma. AB - Diffusely enlarged nonhydronephrotic kidneys on ultrasound and computer tomographic examination in a case of progressive preterminal renal insufficiency were very suggestive of extensive lymphomatous infiltration. Diffuse infiltration of the kidney by centrocytic/centroblastic non-Hodgkin lymphoma was confirmed upon renal biopsy. No other localizations of lymphoma could be found. After four courses of CHOP chemotherapy there was a complete remission of this primary renal non-Hodgkin lymphoma, with complete recovery of renal function. PMID- 1738400 TI - Acute effect of erythropoietin on plasma renin activity and aldosterone levels in end-stage renal disease. PMID- 1738401 TI - Sex chromosome abnormality in chronic renal failure. PMID- 1738402 TI - Retinitis pigmentosa and aortic regurgitation in a patient with adult polycystic kidney disease. PMID- 1738403 TI - Cadmium, hypertension and smoking. PMID- 1738404 TI - Administration of Triton WR 1339 aggravates chronic aminonucleoside nephrosis. PMID- 1738405 TI - Intravenous Fe-gluconate-Na for iron-deficient patients on hemodialysis. PMID- 1738406 TI - Acute interstitial nephritis during continuous intravenous administration of low dose interleukin-2. PMID- 1738407 TI - Gordon's syndrome--hypertension and hyperkalemia associated with normal glomerular filtration rate. PMID- 1738408 TI - Interaction of fluconazole with ciclosporin A. PMID- 1738409 TI - Metabolic study in dysmorphic hematuria. PMID- 1738410 TI - Serum erythropoietin levels in the immediate kidney-posttransplant period. AB - Following successful kidney transplantation, renal anemia is gradually corrected during the first 3-4 months. Serum erythropoietin (EPO) levels are increased after the first postoperative day following grafting. In this study, the serum EPO levels in the early posttransplant phase were investigated in 8 living-donor and 7 cadaveric-kidney transplant recipients with special emphasis on the first 24 h. Despite a considerable difference in cold ischemic time of the graft in the two groups the increase in serum EPO levels was noticed at about the same time (8 h) in both groups and the first peak of serum EPO, which was observed after 24 h, reached the same level in both groups. After 9-11 days, serum EPO reached levels which usually are observed during the first months following transplantation. The EPO response seems to be blunted in relation to the degree of anemia in the early posttransplant phase. PMID- 1738411 TI - Infusion of peripheral blood mononuclear cell products from nephrotic children increases albuminuria in rats. AB - Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p less than 0.001) and a significant increase in urinary albumin excretion (p less than 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability. PMID- 1738412 TI - Inhibition of urea tubular reabsorption by PGE1 infusion in man. AB - We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FCurea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE1 infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE1 at rates of 0.01, 0.05 and 0.1 micrograms/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE1. In study A, FCurea rose by 23% (p less than 0.01) at the lowest PGE1 infusion rate (0.01 micrograms/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE1 infusion rates (0.05 and 0.1 micrograms/min/kg) were associated with a progressive increase of FCurea (50%, p less than 0.001 and 91%, p less than 0.001, respectively), fractional clearance of water and salt output, inulin and PAH clearance and reduced Uosm from 1,005 (22 SEM; basal value) to 772 (38 SEM; minimum value) mosm/kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738413 TI - Effect of thrombocytopenia on the onset of immune complex glomerulonephritis. AB - The effect of platelets on the development of immune complex glomerulonephritis (GN) was examined using bovine serum albumin (BSA) GN with platelet depletion. To clarify the role of platelets in the initial stage of BSA GN, thrombocytopenia was induced before BSA infusion. In 18 New Zealand white rabbits, BSA was intravenously injected twice after the presensitization. Eight of these BSA GN rabbits were injected daily with goat anti-rabbit platelet antiserum to induce thrombocytopenia, and platelet counts were maintained below 5 x 10(4)/microliters throughout the experiment. In the thrombocytopenic group, the degree of proteinuria was significantly decreased compared to the control group. Glomerular polymorphonuclear leukocyte infiltration, mononuclear cell proliferation, exudation and glomerular enlargement were significantly suppressed in the thrombocytopenic group. The results suggest that platelets may be quite important in the initiation and development of immune complex GN. PMID- 1738414 TI - Increased lipid peroxidation in patients on maintenance hemodialysis. AB - Lipid peroxidation products, lipid hydroperoxide and malonaldehyde were measured in the serum of patients on maintenance hemodialysis and compared with values obtained from a group of healthy controls. Dialysis patients had significantly elevated levels of lipid peroxidation products (12.9 +/- 1.9 vs. 9.3 +/- 1.3 nmol/ml, mean +/- SD, patients vs. controls, p less than 0.0001). In contrast, the serum transferrin level was significantly lower in the dialysis patients (217 +/- 71 vs. 290 +/- 50 mg/dl, patients vs. controls, p less than 0.0002). Compared to normal controls HDL cholesterol was lower (40 +/- 11 vs. 53 +/- 8, p less than 0.0001) and triglycerides were higher (206 +/- 103 vs. 142 +/- 64, p less than 0.007) in the patient group. The patient group was then divided on the basis of using polysulfone or cupraphane dialyzers. Patients using polysulfone dialyzers had lower levels of 2-thiobarbituric acid-reactive substances (12.3 +/- 0.9 vs. 13.6 +/- 2.1, polysulfone vs. cupraphane, p = 0.05), and higher transferrin concentrations (248 +/- 84 vs. 194 +/- 37, p = 0.03). Thus, in patients on maintenance hemodialysis there was evidence for accelerated lipid peroxidation. This abnormality was more marked in patients using traditional cupraphane dialyzers. The mechanism for this observation remains unclear. PMID- 1738415 TI - Control of predialytic hyperphosphatemia by oral calcium acetate and calcium carbonate. Comparable efficacy for half the dose of elemental calcium given as acetate without lower incidence of hypercalcemia. AB - Since Mai et al. found, with the intestinal lavage technique, that the same dose of elemental calcium given as acetate (Ca Ac) complexed in the gut of uremic patients twice as much phosphate as calcium carbonate (CaCO3) while inducing a rather low calcium absorption, we wanted to see if half the dose of elemental calcium given as Ca Ac could control, on medium term, the predialysis plasma phosphate as well as CaCO3 while inducing less frequent hypercalcemia. This was evaluated in a cross-over study of 3 periods of 10 weeks according to the sequence Ca Ac, CaCO3 and Ca Ac, in 12 compliant patients on chronic dialysis previously treated by CaCO3. Because of poor tolerance of Ca Ac during the first period, 4 patients were excluded and the results were assessed only on the 8 patients who completed the study. For half the doses of elemental calcium (620 +/ 250 mg versus 1,310 +/- 560 mg versus 710 +/- 200 mg/day), Ca Ac allowed the same control of predialytic hyperphosphatemia (1.67 +/- 0.34; 1.74 +/- 0.32; 1.75 +/- 0.38) with paradoxically comparable normal mean plasma calcium concentration (2.61 +/- 0.14; 2.56 +/- 0.13; 2.55 +/- 0.14 mmol/l). Plasma alkaline phosphatases and intact PTH concentrations remained also stable during the 3 periods. The frequency of hypercalcemia greater than 2.75 mmol/l (12; 9; 20%) and of hyperphosphatemia greater than 2 mmol/l (17; 22; 27%) were comparable with the 2 treatments. In conclusion, Ca Ac controls predialytic hyperphosphatemia as efficiently as CaCO3 for half the dose of elemental calcium without, however, decreasing the frequency of hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738416 TI - Prognostic indicators in childhood IgA nephropathy. AB - A number of clinical, laboratory and pathologic parameters were assessed for their prognostic significance in 200 children aged less than 15 years with IgA nephropathy, who had shown normal renal function at the time of initial biopsy and were followed for more than 2 years thereafter. After a mean follow-up period of 5.0 years from the initial biopsy, 93 patients had no demonstrable abnormality, 76 had minor urinary abnormalities, 21 had persistent heavy proteinuria and 10 had developed chronic renal impairment. A poor outcome was found to be correlated with heavy proteinuria at biopsy, diffuse mesangial proliferation, a high proportion of glomeruli showing sclerosis, crescents or capsular adhesions, the presence of moderate or severe tubulointerstitial changes, and the presence of subepithelial electron-dense deposits and lysis of the glomerular basement membrane by electron microscopy. The percentage of glomeruli displaying crescents, sclerosis and adhesions appeared to be the most reliable prognostic indicator. Nine of the 27 patients (33%) in whom greater than or equal to 30% of glomeruli showed crescents, sclerosis and adhesions developed chronic renal impairment, and only 14% of these patients had normal urine at follow-up. In contrast, only 1 of the 173 patients in whom less than 30% of glomeruli showed such lesions developed chronic renal impairment (p less than 0.001) and 51% of these patients showed complete remission at follow-up (p less than 0.001). These results demonstrate that an accurate prediction of the outcome based on the initial renal biopsy findings is possible early in the course of children with IgA nephropathy. PMID- 1738417 TI - Study on chronic renal injuries induced by carbon tetrachloride: selective inhibition of the nephrotoxicity by irradiation. AB - Carbon tetrachloride (CCl4) was intraperitoneally injected into Balb/c mice 4 times at biweekly intervals, and the morphological changes of the liver and kidney were examined during 12 weeks after the last injection. The renal injuries progressed in spite of cessation of CCl4 treatment; microcysts with tubular-cell degeneration were manifest on day 42 after the last injection of CCl4. At the end of the experiment, however, interstitial fibrosis with inflammatory cell infiltration was much more prominent. Glomerular changes with IgG deposits also developed following the tubulointerstitial changes. The CCl4 treatment induced liver damage as well, but it promptly subsided without formation of cirrhosis. The CCl4 nephrotoxicity was completely inhibited by whole body irradiation (200 rad) exposed at each injection of CCl4. In contrast, the hepatic damage was not changed by irradiation. These results seem to indicate etiologic independence of renal and hepatic events induced by CCl4 treatment. It is also suggested that chronic CCl4 nephrotoxicity is mediated, at least in part, by radiosensitive responses of the mice themselves. PMID- 1738418 TI - Plasma profiles and dialysis kinetics of oxalate in patients receiving hemodialysis. AB - Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated to progressive oxalate accumulation. In view of the controversy still concerning this issue, we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialyzate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Dialysis prescription was set so as to obtain similar KT/V of urea. Mean dialyzer clearance of oxalate (KdOx) was calculated by standard procedures and was compared to urea (KdUrea) and creatinine (KdCr) clearances. Oxalate removal was measured on the whole spent dialyzate. Distribution volume of oxalate (VOx) was estimated by assuming a single-pool model and was used to estimate the oxalate appearance rate (OxAR). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. However, the threshold of supersaturation for calcium oxalate was exceeded in only 13 of 138 (9.4%) assayed ultrafiltrates, 13% on HD and 7.1% on HDF. Dialysis reduced plasma oxalate by more than 60%. There was a postdialysis oxalate rebound averaging 9.6% at 30 min from the end of dialysis. Plasma oxalate predialysis was independent of sex, age and time on dialysis. KdOx was mildly higher on HDF than on HD, and was lower than both KdUrea and KdCr, irrespective of the dialysis technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738419 TI - Intraglomerular proteinase activity in adriamycin-induced nephropathy. AB - Adriamycin (ADR)-induced nephropathy is characterized by focal and segmental glomerulosclerosis and is supposed to be an ideal model of chronic progressive renal disease. The aim of our study was to investigate whether there might be an altered activity of glomerular proteinases in ADR nephropathy, thereby aggravating glomerular protein accumulation as an important initiating hallmark of glomerulosclerosis. In fact, we could demonstrate significantly enhanced levels of intraglomerular protein and DNA content in the experimental animals at week 7, 12 and 22 after administration of ADR. When relating intraglomerular proteinase activity, which was measured in ultrasonically destroyed isolated glomeruli, obtained by differential sieving techniques, to the intraglomerular protein and DNA content, this enzyme activity was significantly reduced throughout the observation period. Based on these data, we suggest that this relatively decreased proteinase activity in glomeruli exposed to ADR might play a pathogenetic role in the development of glomerular hypertrophy, an important harbinger of glomerulosclerosis. PMID- 1738420 TI - Increases in levels of collagen types I and IV messenger ribonucleic acid in murine kidneys after treatment with ciclosporin. AB - We investigated changes in the levels of mRNA transcripts encoding types I and IV collagen in the kidney following the administration of ciclosporin (CS) in mice. Daily doses of CS increased the levels of mRNAs encoding collagen types I and IV in whole kidneys harvested 4 weeks after treatment. At this time point, neither a reduction of renal function detected by serum creatinine, nor histologic evidence of interstitial damage were present. Elevated levels of serum creatinine as well as mild interstitial changes did develop, however, 12 weeks after daily treatment with CS. Collagen type I transcripts were almost normal after 12 weeks, whereas levels of type IV mRNA were still elevated. Our findings indicate that increases in transcripts encoding collagens precede a deterioration in renal function and the development of interstitial changes in this murine model of chronic CS nephrotoxicity. PMID- 1738421 TI - Induction of irreversible glomerulosclerosis in the rat by repeated injections of a monoclonal anti-Thy-1.1 antibody. AB - The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis. PMID- 1738422 TI - [Magnetic resonance imaging in diffuse brain injury]. AB - Forty cases diagnosed as diffuse brain injury (DBI) were studied by magnetic resonance imaging (MRI) performed within 3 days after injury. These cases were divided into two groups, which were the concussion group and diffuse axonal injury (DAI) group established by Gennarelli. There were no findings on computerized tomography (CT) in the concussion group except for two cases which had a brain edema or subarachnoid hemorrhage. But on MRI, high intensity areas on T2 weighted imaging were demonstrated in the cerebral white matter in this group. Many lesions in this group were thought to be edemas of the cerebral white matter, because of the fact that, on serial MRI, they were isointense. In mild types of DAI, the lesions on MRI were located only in the cerebral white matter, whereas, in the severe types of DAI, lesions were located in the basal ganglia, the corpus callosum, the dorsal part of the brain stem as well as in the cerebral white matter. As for CT findings, parenchymal lesions were not visualized especially in mild DAI. Our results suggested that the lesions in cerebral concussion were edemas in cerebral white matter. In mild DAI they were non hemorrhagic contusion; and in severe DAI they were hemorrhagic contusions in the cerebral white matter, the basal ganglia, the corpus callosum or the dorsal part of the brain stem. PMID- 1738423 TI - [Clinical course in poor grade patients with ruptured intracranial aneurysms and extensive subarachnoidal clot]. AB - Three hundred and eight cases with ruptured intracranial aneurysms and variable amounts of subarachnoidal clot were evaluated clinically with special emphasis on the natural course of poor grade patients. Clinical severity was classified according to the Glasgow Coma Scale (GCS); severe cases (score 3-8) and mild cases (score 9-15). Patients were further divided into four groups based on the preoperative clinical course, and on whether radical surgery was performed or not. Group A, severe cases without radical surgery (17 patients, mean GCS score 4.2); group B, severe cases (which had undergone) radical surgery (24 cases, mean GCS score 5.5); group C, patients considered as severe cases on admission that had improved to mild cases before radical surgery (3 patients, mean GCS score 11.7); group D, mild cases which had undergone radical surgery (254 cases, mean GCS score 14.3). CT findings after their last bleeding episode were evaluated in each group using subarachnoid hemorrhage (SAH) score from "0"-"3" according to the severity of SAH. In addition, the SAH-B (brainstem) score ("0"-"9") was also evaluated. In this score, the amount of SAH in each perimesencephalic cistern (a. prepontine or interpeduncular cistern, b. ambient cistern, c. quadrigeminal cistern) was considered with a possible score of "0"-"3" for each cistern. (No patient had a concurrent intracerebral or intraventricular hematoma causing a mass effect on CT scan). All cases in group A died except one patient that remained in a vegetative state. All of them had severe subarachnoidal clot (mean SAH score 2.9, SAH-B score 8.2). In group B, in patients with same scores (mean SAH score 2.8, mean SAH-B score 7.3), the outcome was as follows: 6 patients (33.3%) had full recovery or were capable of self-management, 6 patients (33.3%) were partially or fully dependent, and 12 patients (50%) were either in vegetative state or died. Patients in groups C and D with good outcome had significantly less amount of SAH, especially in the perimesencephalic cistern (group C--mean SAH score 2.3, mean SAH-B score 3.7, group D--mean SAH score 1.9, mean SAH-B score 3.3). It is concluded that duration and level of unconsciousness in the cases of SAH without concurrent hematoma causing mass effect, has a good correlation with the severity of SAH in the perimesencephalic cisterns.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1738424 TI - [Study of meningeal carcinomatosis: diagnosis and treatment]. AB - Thirty-four patients with meningeal carcinomatosis were treated at The Center for Adult Diseases, Osaka, from 1984 through 1990. The major origin of meningeal carcinomatosis was carcinoma of the lung (14 cases) and breast (8 cases). The most frequent histological type of carcinoma was adenocarcinoma (23 cases). Twenty cases still had active lesions and/or primary lesions in the lung, liver or bone at the time of diagnosis of the meningeal carcinomatosis. The primary lesions were treated surgically in 22 cases, with chemotherapy in 4 cases and with radiotherapy in 2 cases. Metastatic brain tumors were treated by surgical removal followed by chemo-radiotherapy in 12 cases, and with radiotherapy alone in 2 cases. The interval from the time of diagnosis of the primary lesion to the time of diagnosis of the meningeal carcinomatosis varied from one month to eight years, and the interval between surgical removal of metastatic brain tumors and the diagnosis of meningeal carcinomatosis ranged from 0 to 3 years. With regard to the diagnosis of meningeal carcinomatosis, positive cytology was seen in initial standard lumbar puncture in 32 of the 34 patients. CT scan showed abnormal findings in 28 of the 34 patients, including ventricular dilatation only (12 cases), and small enhancing lesions along the CSF space (12 cases). The EEG showed abnormal patterns in 14 of 15 cases. Intrathecal chemotherapy with methotrexate alone or combined methotrexate with cytosine arabinoside via the Ommaya reservoir or standard lumbar puncture alternately with or without radiation therapy was successful as treatment, and 22 of 29 treated patients showed symptomatic improvement of the meningeal irritation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738425 TI - [Study on the extent of peritumoral edema in glioma: its correlation with the proliferative potential and tumor-infiltrating mononuclear cells]. AB - The correlation between the extent of peritumoral edema and the proliferative potential or the infiltration of mononuclear cells was studied in 17 gliomas. The peritumoral edema was evaluated on contrast enhanced CT scan as the ratio of the low density area around the tumor to the enhanced high density area. The proliferative potential and the infiltration of mononuclear cells into the tumor were investigated immunohistochemically using monoclonal antibody (MAb) against DNA polymerase alpha and anti-Leu MAb's respectively. There was a significant correlation between the extent of the peritumoral edema and the percentage of DNA polymerase alpha positive cells. The degree of the infiltration of mononuclear cells into the tumor tissue also correlated with the extent of peritumoral edema. In gliomas with high proliferative potential and/or severe infiltration of mononuclear cells, the peritumoral edema may be aggravated by disruption of the blood-brain-barrier and increased vascular permeability. PMID- 1738426 TI - [Two cases of von Recklinghausen's disease with multiple brain and spinal tumors]. AB - The authors reported two cases of von Recklinghausen's disease with multiple brain tumors and multiple spinal tumors. The first case, a 21-year-old man who had a past history of optic gliomas was admitted because of gait disturbance. Computed tomography (CT) and magnetic resonance imaging (MRI) showed calcification of the basal ganglia, bilateral C-P angle tumors, cystic cerebellar tumor and arachnoid cyst in the quadrigeminal cistern. Myelography and MRI revealed multiple spinal tumors. Surgical management was performed and cerebellar tumor was histologically confirmed to be a pilocytic astrocytoma. Spinal tumors were also astrocytomas. The second patient, a 56-year-old woman suffered from right iliac pain, right hemiparesis and motor aphasia. CT revealed two round tumors in the left cerebral hemisphere and bilateral C-P angle tumors. Myelography and MRI demonstrated multiple intradural-extramedullary spinal tumors. Histologically, supratentorial tumors were transitional meningiomas and spinal tumors were neurinomas. It is well known that von Recklinghausen's disease is often associated with brain or spinal tumors. But, in the literature, only 22 cases of von Recklinghausen's disease combined with multiple brain tumors with different histological types and multiple spinal tumors have been reviewed. With our two cases, the average age of these 24 cases was 28.6 years old, nine cases were male and 15 cases were female. All patients had C-P angle tumors and 23 cases were combined with intracranial meningiomas. In this paper, the clinical features and diagnostic aspects were discussed. PMID- 1738427 TI - [Radiosensitive malignant meningioma presenting Garcin's syndrome: a case report]. AB - A 58-year-old woman with Garcin's syndrome caused by malignant meningioma is reported. She first noticed left facial hypesthesia followed by left visual disturbance with exophthalmos. CT scan showed an enhanced mass extending from the left cavernous sinus to the left orbit. Cranial x-ray revealed bone deformity around the orbit. The tumor was subtotally resected and its histological type was shown to be anaplastic meningioma. After the initial surgery the patient was left with hyposmia, mild ptosis and incomplete 6th cranial nerve palsy on the left side. After one and half years, not only palsy of those cranial nerves but also that of other unilateral cranial nerves became progressively apparent due to tumor regrowth. In total, 11 nerves (2nd-12th) were affected by the tumor, without long tract signs or symptoms of increased intracranial pressure. Radiation therapy carried out after the 2nd surgery was extremely effective and resulted in the recovery of lower cranial nerve function. The tumor was founded to have disappeared completely on the 2-year follow-up CT. PMID- 1738428 TI - [A case of hypothalamic astrocytoma with precocious puberty]. AB - A case of hypothalamic astrocytoma with precocious puberty is presented. In July 1989, a 2-year-old girl was admitted to our hospital because of vaginal bleeding and enlargement of breasts. Breast development was Tanner's stage 3 and no pubic hair was present. Endocrinological evaluation revealed a slightly high level of LH, but the responses of LH and FSH to LH-RH test resulted in exceedingly high values similar to those in adults. Plain CT scan showed an isodense mass in the suprasellar cistern which was not enhanced following administration of contrast medium. MR imaging revealed the precise location of the mass attached to the posterior hypothalamus between the pituitary stalk and the mamillary bodies in sagittal view. The signal intensity of the mass was homogenous and isointense relative to the gray matter on T1 weighted image. But on T2 weighted image, it showed high signal intensity compared with the normal brain parenchyma. A right fronto-temporal craniotomy was performed and the tumor was partially removed. Histological examination disclosed moderate hypercellularity of glial cells but no neurons were visible. This appeared to be astrocytoma grade II. In the literature, CT and MRI behaviour of hypothalamic hamartomas are almost similar to our case. Therefore we think it is not possible at the present time to differentiate a low grade astrocytoma from hamartoma when using CT and MRI alone. In this case, the mechanism of development of precocious puberty seemed to be due to hypothalamic compression by the tumor. PMID- 1738429 TI - [Two cases of lateral approach for thoraco-lumbar junctional lesions: experiment of Kaneda's device]. AB - Case 1: a 32-year-old woman was admitted to our hospital with major complaints of gait disturbance and urinary incontinence. The tendon reflex was markedly increased in the bilateral lower extremities, and both Babinski's reflex and clonus were strongly positive. Myelography revealed complete block in the 10th thoracic vertebral level. On April 15, 1989, a tumor in the vertebral region was exposed and excised via a right posterolateral approach. Kaneda's device was used for internal fixation. The tumor was diagnosed as myeloma histologically. The postoperative course was uneventful. Postoperatively, the patient became capable of walking by herself. Case 2: an 18-year-old woman was admitted because of burst fractures of the 1st and 2nd lumbar vertebrae due to a traffic accident in January of 1989. The fractured bones had been manually repositioned and fixed with plaster. However, the patient still had gait disturbance (intermittent claudication). Myelography revealed a complete block in the 2nd lumbar vertebral region. On May 7, the vertebral foramen was opened via a left anterolateral approach, and internal fixation was performed using Kaneda's device. Postoperatively, the patient recovered full ability to walk, and returned to normal social activity. From our experience, it is thought to be useful to employ a right posterolateral approach to the thoracic vertebrae, and a left anterolateral approach to the lumbar vertebrae. We used Kaneda's device for internal fixation, successfully. However, this device has the following disadvantages; (1) there are few plates designed for females, whose vertebrae are small, (2) it is difficult to preserve the arteries of Adamkiewicz and (3) postoperative MRI becomes impossible. PMID- 1738430 TI - [Postoperative intracranial hemorrhage due to vitamin K deficiency: report of two cases]. AB - Vitamin K deficient hemorrhagic diathesis is well known as a cause of infantile intracranial hemorrhage. Its occurrence, however, as a post-surgical complication is rare and has never been reported previously. Two cases are presented here which illustrate the existence of such a hazard. Case 1. A 73-year-old woman admitted with subarachnoid hemorrhage (WFNS IV) underwent microsurgical exploration of a left internal carotid aneurysm, and neck clipping of the aneurysm was performed. She had an uneventful postoperative course, but her neurological condition deteriorated suddenly on the fifth postoperative day. CT scan revealed a large epidural hematoma. Case 2. A 6-year-old boy was admitted due to the dysfunction of a ventriculo-peritoneal shunt system that had previously been placed for hydrocephalus. This dysfunction was thought to be caused by meningitis. Twelve days after ventricular drainage and antibiotic therapy, sudden intraventricular hemorrhage occurred. In both cases, PT and APTT were markedly prolonged, FDP slightly increased and fibrinogen slightly decreased. SFMC was positive in case 2. After the administration of vitamin K, PT and APTT were immediately normalized. Recent reports emphasize the adverse effect of antibiotics that leads to vitamin K deficient hemorrhagic diathesis, especially, in patients in a cachectic state. In these two cases, such a cachectic condition was not observed. We presume that the cause of vitamin K deficiency would be, along with the administration of antibiotics, a preliminary condition of disseminated intravascular coagulation which is encountered in some neurological disorders including subarachnoid hemorrhage. We conclude that attention should be paid for these pitfalls in perioperative neurosurgical care. PMID- 1738431 TI - [Histological diagnosis of brain tumors: (19). Medulloblastoma]. PMID- 1738432 TI - [CT findings in "fresh" cerebral paragonimiasis]. AB - There are few reports on CT findings in "fresh" cerebral paragonimiasis. We have experienced four cases of "fresh" cerebral paragonimiasis examined by CT scan. Three patients were children aged 7, 9, and 14 years, and one was an adult aged 25 years. Three patients were examined by CT scan 2 to 6 months after the onset of high grade fever, convulsion and focal deficit signs, and a patient was examined one month after his progressive visual disturbance. The unique CT findings are multilocular cystic lesions in temporo-occipital or in temporo parietal lobes with extensive brain edema. Two cases were also associated with "soap-bubble" calcifications. The cysts were more dense than CSF and enhanced by contrast media. The histopathological specimen showed that the eggs of paragonimus were in the abscess cavity, of which the wall was composed with highly vascular gliomesenchymal capsule and numerous cell infiltration. Three patients underwent craniotomy for removal of abscess and decompression. Bitionol were administered and all patients recovered well. We also discussed the differential diagnosis of cerebral parasitic granulomas. PMID- 1738433 TI - Thyroid hormones regulate the formation of inositol phosphate in response to thyrotropin-releasing hormone in rat anterior pituitaries. AB - The effects of thyroid hormones on TSH secretion and inositol phospholipid hydrolysis in response to thyrotropin-releasing hormone (TRH) in rat anterior pituitaries were examined. Experimental hypothyroidism caused a significant increase in [3H]inositol phosphate ([3H]IP) formation in response to TRH in rat anterior pituitaries with a concomitant elevation of blood TSH. In contrast, administration of thyroxine (T4) to hypothyroid rats resulted in a complete restoration of blood TSH and TRH-stimulated [3H]IP formation to the euthyroid control value. Furthermore, in vitro pre-treatment of anterior pituitaries with triiodothyronine (T3) produced a dose-dependent decrease in both TSH secretion and the formation of [3H]IP in response to TRH. These results indicate that thyroid hormones regulate TRH receptor-linked inositol phospholipid hydrolysis in the rat anterior pituitary, suggesting that negative feedback action of thyroid hormone occurs at post receptor event in the rat anterior pituitary, which may, to a certain extent, be responsible for the underlying mechanism of T3 inhibition of TSH secretion. PMID- 1738434 TI - Effect of diabetes on the levels of two forms of Met-enkephalin in plasma and peripheral tissues of the rat. AB - Levels of native and cryptic or peptidase-derivable (after being digested with trypsin and carboxypeptidase) Met-enkephalin were measured by a specific radioimmunoassay method in plasma, anterior and neurointermediate lobes of pituitary and various peripheral tissues of streptozotocin (STZ) diabetic rats. The results show that the highest concentration of native and cryptic Met enkephalin were found in the neurointermediate lobe of pituitary. Streptozotocine induced diabetes alters the concentration of either or both forms of Met enkephalin in plasma, the anterior and neurointermediate lobes of the pituitary, heart, lung, spleen, liver, seminal vesicle, vas deferens, kidney, bladder detrusor, and duodenum. One of the most pronounced effects of diabetes observed in this study is seen in the seminal vesicles where native Met-enkephalin was depleted to less than 10% of the control value. The uneven distribution of Met enkephalin in peripheral tissues may suggest that these tissues process and/or metabolize Met-enkephalin to different degrees. Our data also suggest that STZ induced diabetes alters the enkephalinergic activity in some of these tissues. It is suggested that some of the peripheral pathophysiological symptoms associated with diabetes may be attributed, in part, to altered activity of enkephalinergic systems. PMID- 1738435 TI - Cavernous sinus hemangiomas: a series, a review, and an hypothesis. AB - Cavernous sinus hemangiomas represent 3% of all benign cavernous sinus tumors. They are dangerous tumors because of the risk of excessive bleeding, but they are easier to dissect from surrounding structures than meningiomas because of the presence of a pseudocapsule. Three cases where total excision was achieved with minimal blood loss, without stroke, and with preservation of cranial nerve function in 2 cases are reported, and 50 cases from the literature are reviewed. Hemangiomas can be distinguished preoperatively from over one-half of meningiomas by their marked hyperintensity on T2-weighted magnetic resonance imaging. They arise within the cavernous sinus and extend laterally by dissecting between the two layers of dura lining the floor of the middle fossa. Cranial nerves III, IV, and V remained stretched over the tumor surface within the overlying dura, whereas cranial nerve VI is found within the tumor and is the most difficult cranial nerve to preserve. Principles for successful and safe excision include preoperative assessment of the safety of temporary or permanent carotid artery occlusion, obtaining early proximal carotid artery control, carefully developing the plane between the dura and the tumor pseudocapsule, early devascularization of the tumor, and avoiding "piecemeal" tumor resection. A few cases demonstrated tumor shrinkage with radiation therapy which should be considered for patients with incomplete tumor excision or who are too ill to undergo surgery. PMID- 1738436 TI - Spontaneous spinal epidural hematoma causing paraplegia: resolution and recovery without surgical decompression. AB - Spontaneous spinal epidural hematomas are well-recognized but rare entities. The standard treatment for these hematomas has been prompt surgical evacuation. The authors report a case of a 76-year-old man who precipitously became paraplegic secondary to a spontaneous spinal epidural hematoma and then experienced the complete resolution of his neurological deficit and the hematoma. We conclude that conservative (nonoperative) management of spontaneous spinal epidural hematomas may be appropriate in those instances in which there is early and sustained neurological recovery confirmed by radiological resolution of the lesion. PMID- 1738437 TI - Postlaminectomy lumbar pseudomeningocele: report of four cases. AB - Pseudomeningocele formation is unusual after a lumbar discectomy. Four patients who developed a pseudomeningocele after lumbar disc surgery are reported. The pseudomeningocele was symptomatic in three patients. The diagnosis of a pseudomeningocele was made by computed tomography in conjunction with myelography in three patients and magnetic resonance imaging in the fourth. All patients underwent surgery for the pseudomeningocele with primary closure of the dural defect (the patient whose meningocele was asymptomatic also had an excision of an extruded disc), and postoperative results were gratifying. PMID- 1738438 TI - Spinal intramedullary subependymomas: case report and review of the literature. AB - A cervical spinal intramedullary subependymoma in a 53-year-old man is reported, and the relevant literature is reviewed. Spinal cord subependymomas seem to follow a benign course. Radiotherapy should not be administered to these patients. Magnetic resonance imaging, even with enhancement, is not able to distinguish between a subependymoma and the more common ependymoma. PMID- 1738439 TI - Intramedullary epidermoid associated with an intramedullary spinal abscess secondary to a dermal sinus. AB - Intramedullary spinal abscesses are rare and potentially devastating lesions. A heightened clinical awareness of patients at risk is essential for an early diagnosis and intervention to improve the prognosis of these patients. The first case of spinal abscess was described in 1830, and only 63 cases have been reported subsequently. Intraspinal epidermoids also are unusual lesions. These tumors were reported first in 1829 and represent less than 1% of all intraspinal tumors. We present a case of a 2-year-old girl who had rapidly progressive paraplegia with urinary and bowel retention and was found to have an intramedullary epidermoid and an intramedullary abscess as a result of a dermal sinus. The association of an intramedullary abscess and epidermoid tumor, two rare lesions, has not been reported previously. We also review the literature related to both intramedullary epidermoids and intramedullary abscesses of the spinal cord. Advances in sectional imaging as described should help lead to an early and safe diagnosis of these rare but often debilitating lesions. This case illustrates the importance of a complete neurological assessment of all patients with a congenital dermal sinus because of the potential for intradural extension and the frequent association with other dysraphic abnormalities. Prophylactic surgery is indicated in many cases to prevent dangerous and recurrent infections of the central nervous system. PMID- 1738440 TI - Prophylactic hypervolemia without calcium channel blockers in early aneurysm surgery. AB - Delayed ischemic neurological deficit (DIND) remains a major unsolved problem in the management of aneurysmal subarachnoid hemorrhage (SAH). For many years, the complications reported with acute aneurysm surgery caused surgeons to operate late after SAH. In a 42-month-period, we managed 146 patients with aneurysm and/or SAH. Forty-seven patients were characterized by the following: Hunt and Hess Grades I through III after an aneurysmal SAH; 2) clipping of their aneurysm within 72 hours of their SAH; and (3) prophylactic hypervolemia with a pulmonary artery catheter to optimize their fluid management. Forty of 47 (85%) had an excellent or good outcome, and 3 of 47 (6%) died. All of those who died had DIND. Nine of 47 (19%) patients developed DIND. There were 20 complications, primarily pulmonary edema, in 16 patients and one death related to prophylactic hypervolemia. It is not clear from our experience, when compared with results from other series, that hypervolemia provides any additional benefit to the patient as measured by a reduction in the risk of DIND or improved outcome. Despite aggressive volume expansion to the point of cardiovascular compromise, as evidenced by our high rate of pulmonary edema, we had no appreciable decrease in neurological morbidity and mortality when compared with results from recent reports. PMID- 1738441 TI - Intramedullary abscess associated with a spinal cord ependymoma: case report. AB - Intramedullary spinal cord abscesses are relatively uncommon. We report the first case of an intramedullary spinal cord abscess in a preexisting spinal cord ependymoma. The clinical features and pathogenesis are discussed. Salient features of the management of intramedullary spinal cord abscesses are outlined. PMID- 1738442 TI - Traumatic spondylolisthesis of the lower cervical spine: case report. AB - A case of traumatic spondylolisthesis of C6 and C7 is presented. The mechanism of injury and the therapeutic implications are discussed. PMID- 1738443 TI - Spinal cord compression in Scheuermann's kyphosis: case report. AB - Compression of the spinal cord secondary to disc disorders in Scheuermann's kyphosis is rare. This review reports an unusual case emphasizing mechanisms of compression of the spinal cord from this disc disorder. Contrasts and comparisons with previously published cases are included. PMID- 1738444 TI - Video endoscopic sympathectomy using a fiberoptic CO2 laser to treat palmar hyperhidrosis. AB - Palmar hyperhidrosis is a common disorder among orientals. A new therapeutic technique for this disorder has been designed by combining a computer compact disc video endoscopic system with a fiberoptic CO2 surgical laser unit. The operation is performed under general anesthesia with alternating one-lung ventilation. There are three important aids in localizing the correct sympathetic segment: 1) direct visualization of its magnified image on the television monitor; 2) identification with an electrode probe palpation at its presumed location; and 3) monitoring the microvasomotor changes on the skin of the finger resulting from electrical stimulation of the sympathetic trunk. Subsequently, the confirmed sympathetic target is vaporized using a low power CO2 laser under direct vision on the television monitor. The laser is delivered to the target by a small optical fiber passing through a throacoscope, which is introduced into the thoracic cavity via the intercostal space between the second and third ribs at the midclavicular line. Fourteen palmar hyperhidrosis patients were successfully treated by this method. No complications, such as Horner's syndrome, bleeding, or intercostal neuralgia, were encountered. Although the number of cases treated was small, and the follow-up period was short, the evidence indicates that a definite sympathectomy on a confirmed segment under magnified vision is possible with this procedure, and could warrant a definite and long lasting therapeutic effect. Based on our experience, the method is considered a relatively minor and safe procedure, causing minimal discomfort and almost invisible scars. The operation time and hospital stay were remarkably shortened in comparison with other conventional sympathectomy procedures. PMID- 1738445 TI - Partial callosal resection for pericallosal aneurysms. AB - The surgical treatment of aneurysms that arise at the origin of the pericallosal artery is technically difficult. This report describes a technique that improves the exposure of the proximal vasculature during a craniotomy for pericallosal aneurysms. A portion of the corpus callosum was resected in two patients before the manipulation of their aneurysms. The resection provided excellent exposure of the A2 segment of the anterior cerebral artery, and both aneurysms were clipped safely. Neither patient exhibited signs of hemispheric disconnection. The authors conclude that partial callosal resection improves access to the proximal vessels during procedures for pericallosal aneurysms. PMID- 1738446 TI - A simple and reliable technique to monitor intracranial pressure in the rat: technical note. AB - A technique for intracranial pressure (ICP) monitoring in the rat that uses a permanent cisterna magna cannula is described. The cannula is placed into the subarachnoid space through the atlanto-occipital membrane with the operating microscope and is secured with cement. The distal end is connected to a pressure transducer and a polygraph recorder. To study the consistency of this technique, 12 anesthetized adult rats were subjected to baseline ICP measurements 2 days after placement of the cannula. Baseline pressures ranged between 1.0 and 10.0 cm H2O, with a mean of 5.6 cm H2O. Respiratory variations were detected in all tracings, and manual abdominal compressions (Valsalva maneuver) correlated with immediate transient rises in ICP in all rats. While CSF pressure was being continuously monitored, rats were subjected to subarachnoid hemorrhage induced by transclival basilar artery puncture. Of the 12 rats, 10 showed a moderate transient rise in cerebrospinal fluid pressure, which peaked approximately 2 minutes after subarachnoid hemorrhage (mean peak change, 10.5 cm H2O; range, 0 32.5 cm H2O). Reliable pressure tracings were obtained in three of five animals examined 3 days after subarachnoid hemorrhage (ICP range, 4.0-4.5 cm H2O; mean, 4.2 cm H2O). We conclude that this cannula is easy and inexpensive to construct and that it provides reliable ICP tracings during experimental procedures in the rat. PMID- 1738447 TI - Complete temporal lobectomy for surgical resuscitation of patients with transtentorial herniation secondary to unilateral hemisphearic swelling. PMID- 1738448 TI - Transplantation of adrenal medulla and omentum to the putamen by a transinsular pathway for Parkinson's disease. PMID- 1738449 TI - Prolonged lumbar spinal drainage after the resection of tumors of the skull base: a cautionary note. PMID- 1738450 TI - Role of prostaglandins in delayed cerebral ischemia after subarachnoid hemorrhage. AB - Prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha were assayed in blood and cerebrospinal fluid samples from patients after subarachnoid hemorrhage (SAH) and from a control population. The levels found in samples obtained from patients after SAH were compared with those found in controls and were also correlated with a number of clinical and radiological variables, many of which are either significantly associated with or represent evidence of cerebral ischemia. The levels of prostaglandin E2, thromboxane B2, and 6-oxo prostaglandin F1 alpha in blood samples from patients after SAH and from controls were below the level of sensitivity of the assays. Levels of prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha in cerebrospinal fluid from patients after SAH were significantly elevated when compared with those found in control samples. There was no significant correlation, however, between the level of each prostaglandin measured and the following variables: clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons grading system; the amount of subarachnoid blood seen on computed tomographic scan; the occurrence of ischemic deterioration; the occurrence of low density change on computed tomographic scan; the presence of vasospasm on angiography; clinical outcome as assessed by the Glasgow Coma Score 3 months after the ictus; and the incidence of ischemia as a cause of death or disability as assessed 3 months after the ictus. A primary role for prostaglandins in the etiology of delayed cerebral ischemia after SAH is not therefore confirmed. PMID- 1738451 TI - Neuropsychological assessment outcomes of nonacquired immunodeficiency syndrome patients with primary central nervous system lymphoma before and after blood brain barrier disruption chemotherapy. AB - The risk of neurotoxicity was evaluated in eight consecutive patients with non acquired immunodeficiency syndrome (AIDS) primary central nervous system lymphoma who had survived disease free for more than 1 year after completion of treatment with osmotic opening of the blood-brain barrier and chemotherapy (methotrexate, cytoxan, procarbazine, and decadron). Trends in neuropsychological assessment results between baseline and follow-up (1 to 7 years) were analyzed for all eight nonradiated survivors. This serial assessment design addressed the specific issue of neurotoxic risk potential of treatment, when confounding factors of tumor persistence/recurrence and cranial irradiation were ruled out. Follow-up results of an extensive battery of tests to assess higher cortical function provided evidence of the safety of chemotherapy protocol with the blood-brain barrier disruption. These findings stand in contrast to well-known cognitive risks associated with cranial radiotherapy. Long-term follow-up suggests that chemotherapy can be given in conjunction with osmotic opening of the blood-brain barrier in nonradiated patients without cognitive manifestations of neurotoxicity. PMID- 1738452 TI - Quantitative study of blood-brain barrier permeability changes after experimental whole-brain radiation. AB - Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation are not known precisely. We investigated the possibility of a change in blood-brain barrier (BBB) function as a causative factor for early delayed whole-brain radiation-induced cerebral dysfunction. Rats were exposed to conventional fractionation (200 cGy/d, 5 d/wk; total dose, 4000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha aminoisobutyric acid technique and electron microscopy. Studies of the passage of horseradish peroxidase across the BBB permitted comparative quantitative isotopical and qualitative morphological data. Experiments were carried out 2 to 3 weeks after the completion of the radiation exposure. The transport of 14C alpha-aminoisobutyric acid across the BBB increased significantly in cerebral cortex and cerebellar gray matter, averaging 1.3 to 1.5 times over the normal values. Electron microscopy disclosed an intense vesicular response of the cortical microvascular endothelium that occurred without the opening of the tight junctions and resulted in an intense transport of HRP across the intact endothelium. The present data indicate that moderate doses of whole-brain radiation induce well-defined changes in BBB function, which possibly are involved in the pathogenesis of radiation-induced cerebral dysfunction in humans. PMID- 1738453 TI - Intradural extramedullary cysts of the spinal canal: clinical presentation, radiographic diagnosis, and surgical management. AB - Fourteen patients with intradural extramedullary cysts of the spinal canal are described. Histological classification included 11 arachnoid, 2 epithelial, and 1 ependymal cyst. There were 9 thoracic, 3 cervical, and 2 lumbar cysts. The most common clinical presentation was a slowly progressive myelopathy. Twelve patients (85%) had objective neurological findings at the time of diagnosis. Radiographic diagnosis was made by a combination of myelography, computed tomographic scan with myelography, and magnetic resonance imaging. Complete surgical resection was accomplished for 8 dorsal cysts, and 6 ventral cysts were widely fenestrated into the subarachnoid space. Overall results were considered excellent or good in 9 patients, fair in 3, and poor in 2. There was one recurrence, which required a second operation. We conclude that the majority of intradural spinal cysts can be successfully managed surgically with a favorable clinical outcome. PMID- 1738454 TI - Myelographic and enhanced computed tomographic appearance of acute traumatic spinal cord avulsion. AB - The neuroradiological findings that revealed spinal cord transection/laceration in 6 patients with acute, blunt spinal trauma are described. Four patients suffered cervical spine injuries, and two had thoracic injuries. Initially, all patients had complete neurological deficit at the level of injury. The deficit improved in only 1 patient. On the basis of clinical history and spinal radiographs, spinal hyperflexion with distraction was the predominant mechanism of injury in our patients. Computed tomography with intrathecal contrast was performed on all patients and was always diagnostic. Visualization of intrathecal contrast material accumulating within the cord or the absence of cord shadow within the contrast column established the diagnosis in all cases. A dural tear was noted in 3 patients. Thoracic myelography was performed in 2 patients and, in both, demonstrated contrast pooling within the spinal cord at the level of the laceration. Magnetic resonance imaging was obtained in 1 patient and revealed an irregular, low-signal-intensity, intramedullary region extending to the cord surface on T1-weighted axial images. The myelographic and enhanced computed tomographic appearances of acute, traumatic spinal cord avulsion/laceration, which have been infrequently reported in the literature, are described. PMID- 1738455 TI - Microvascular decompression for hemifacial spasm: analyses of operative findings and results in 310 patients. AB - The operative findings and results of microvascular decompression (MVD) on 310 Chinese patients with hemifacial spasm are analyzed in this report. The operations were performed at the Neurological Institute of the Veterans General Hospital-Taipei between January 1983 and June 1990. The length of follow-up ranged from 6 months to 8 years (mean, 4.3 years); 273 patients (88%) had complete relief of spasm within 3 days after one MVD, and the remaining 37 patients (12%) showed no immediate postoperative improvement. Sixteen (5.2%) of these 37 initially unresponsive patients subsequently experienced complete relief, which occurred from 4 days to 22 months (median, 21 days) after one MVD; 13 others (4.2%) had complete relief immediately after the second MVD; another 3 (1%) had delayed complete relief 6, 9, and 11 months after the second MVD, respectively; and the remaining 5 (1.6%) only had delayed partial relief, which occurred 2 to 9 weeks after one MVD. Late recurrence occurred in three patients (1%). These immediate and long-term results lend support to the conclusion that the timing of reoperation can be postponed for a period of 3 to 4 weeks in the event of an initial failure to get improvement, and that a second MVD may be of value. PMID- 1738456 TI - Benign cerebellar astrocytomas of childhood. AB - Benign cerebellar astrocytomas of childhood are potentially surgically curable lesions. Histologically, these neoplasms can be divided into pilocytic and diffuse astrocytomas. Whether there is a difference in the recurrence rate between these two tumor types after a surgical resection is not clear. In addition, the role of immediate postoperative imaging in predicting a recurrence has not been established. To answer these questions, we have reviewed the charts of 23 patients with benign cerebellar astrocytomas treated at Childrens Hospital of Los Angeles over a 10-year period (1977-1987). Of the 23 tumors, 15 were pilocytic and 8 were diffuse. All patients underwent an attempted gross total surgical removal of the tumor, and all patients had a postoperative computed tomographic (CT) scan with and without intravenously administered contrast material performed within 72 hours of the operation. Based on the postoperative CT scan, 12 patients had residual tumors. Seven of the subtotally resected tumors were pilocytic (7 of 15), and 5 were diffuse (5 of 8). Interestingly, the surgeon believed that a gross total resection had been obtained in 9 of these patients. There have been 4 recurrences in these 23 patients, with a mean follow-up of 4.9 years. All recurrences were in patients with subtotal resections. Of the 11 patients with a total resection of the tumor, 7 developed a small rim of enhancement on subsequent scans an average of 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738457 TI - Dissemination of supratentorial malignant gliomas via the cerebrospinal fluid in children. AB - Of 100 children with supratentorial gliomas (excluding gliomas of the anterior visual pathways) treated at the Children's Hospital of Pittsburgh from 1980 to 1990, 34 had malignant gliomas. Follow-up was adequate in 33 of these patients, and an antemortem diagnosis of dissemination of the malignant glioma via the cerebrospinal fluid (CSF) was made in 11. Of these 11, 8 were boys and 3 were girls; they ranged in age from 17 months to 16 years at the time of diagnosis of the primary glioma. The distribution of histological types was as follows: glioblastoma multiforme, 4; malignant oligodendroglioma, 3; anaplastic astrocytoma, 2; malignant mixed glioma, 1; and malignant ependymoma, 1. The interval between diagnosis and CSF dissemination ranged from 1 week to 59 months (median, 8 months). Survival after dissemination ranged from 3 weeks to 11 months (median, 4 months). Two patients were alive 5 and 3 months after diagnosis of dissemination, respectively. These 11 patients were compared with the other 22 patients who did not have CSF dissemination. The risk factors for dissemination suggested by our data were male sex, ventricular operative entry, multiple resections, and malignant oligodendroglioma. Because of the high incidence (33%) of CSF dissemination, postoperative evaluation of the craniospinal axis with gadolinium-enhanced magnetic resonance imaging should be performed on all children with supratentorial malignant gliomas. Moreover, since the mortality is extremely high once dissemination has occurred, craniospinal irradiation should be considered in children with one or more of the above risk factors, even before symptoms or definite radiological evidence of CSF dissemination emerge. PMID- 1738458 TI - Minor leak before rupture of an intracranial aneurysm and subarachnoid hemorrhage of unknown etiology. AB - Of 312 consecutive patients who were admitted to an emergency hospital because of subarachnoid hemorrhage (SAH), data on premonitory minor leaks were available on 303. Patients with an aneurysmal SAH had significantly (P less than 0.05) more frequently (100 of 273, or 37%) a history of symptoms consistent with a previous minor leak than those with a hemorrhage of unknown etiology (4 of 30, or 13%). Aneurysmal SAH was associated with a poorer prognosis, more frequent occurrence of repeated bleeding and cerebral ischemia compared with SAH of unknown etiology, even in the good grade patients. The possible occurrence of a minor leak in poor grade patients may be even more frequent because the history obtained from family members was quite often uncertain. The outcome did not differ according to the evidence of previous minor leaks, but those who were admitted before a major rupture had a good outcome. The median time between a minor leak and major rupture was 14 days (range, 1 day to 4 mo). The correct diagnosis of a minor leak is important because early diagnosis and management can improve the overall outcome of this disastrous disease. PMID- 1738459 TI - Intraoperative monitoring of the dorsal sacral roots: minimizing the risk of iatrogenic micturition disorders. AB - In 31 children (age, 2-17 years) and 1 adult, individual dorsal root action potentials (DRAPs) from the S1-S3 roots were recorded intraoperatively after electrical stimulation of the dorsal penile or clitoral nerves, in preparation for surgery within the cauda equina. In most patients, pudendal afferent activity was present in S2 and S3 bilaterally; in some, the afferent activity was confined to a single root bilaterally, and in one, to a single root on one side. Dorsal root action potentials of small amplitude were recorded from S1 in 15 patients, although in no patient was S1 the primary carrier of these afferents. No lesion of the roots or rootlets carrying significant afferent activity was created during the rhizotomy, and no dysfunction in micturition resulted. We propose that the neurophysiological identification of roots and rootlets carrying afferent activity from the penile or clitoral nerves allows for rhizotomy of the S2 roots with the least possible risk of postoperative micturition and sexual dysfunction. PMID- 1738460 TI - The effect of graded spinal cord injury on the extrapyramidal and pyramidal motor evoked potentials of the rat. AB - This study investigated the differential effects of graded spinal cord injury on the rat extrapyramidal motor evoked potential (exp-MEP) and pyramidal motor evoked potential (pyr-MEP) and the prognostic value of these effects in predicting postinjury motor performance in the rat model. In 20 rats subjected to graded spinal injury (10-100 g-cm), there was a differential injury threshold for ablation of exp-MEP and pyr-MEP. All peaks of the pyr-MEP were extinguished in the animals subjected to impact forces of 50 g-cm and above (n = 12). In contrast, the exp-MEP was completely abolished in only two animals at injuries of 80 g-cm or above. A residual exp-MEP response persisted in the remaining 18 animals. Motor performance was monitored in 16 additional animals for up to 1 week after spinal injury. The pyr-MEP was abolished in 100% of the rats subjected to a 50-g cm injury (n = 7), whereas the exp-MEP persisted up to the highest impact forces (80 g-cm). Hind leg paralysis was present in the five rats where the pyr-MEP was extinguished but with persistence of the exp-MEP. An 80% reduction in the amplitude of the pyr-MEP in four animals resulted in mild ataxia with motor improvement at the end of a week. An increase or a 70% loss in pyr-MEP peak amplitude resulted in no clinical motor deficits (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738461 TI - Influence of some anesthetic agents on muscle responses to transcranial magnetic cortex stimulation: a pilot study in humans. AB - The effects of some commonly used intravenous and inhalational anesthetic agents on the motor evoked responses to transcranial magnetic cortex stimulation were assessed in 17 subjects. Compound motor action potentials (CMAPs) of the abductor digiti minimi muscle were recorded. Baseline values (12 stimulations/subject) were established before anesthesia was induced with a single agent administered in steps up to a maximal dose (MaxDose). Cortical stimulation was performed and depth of anesthesia was assessed according to Guedel after each dose. A common feature was the marked intra- and interindividual variability of baseline values of CMAPs in those patients not premedicated, those premedicated, and the anesthetized patients. The average amplitude of CMAPs was related to the depth of anesthesia in a given subject, whereas onset latencies of CMAPs did not systematically change. CMAPs were markedly reduced or abolished after administration of potent sedative drugs such as midazolam (MaxDose, 0.4 mg/kg body weight), pentothal (MaxDose, 8 mg/kg), propofol (MaxDose, 2 mg/kg), and isoflurane (MaxDose, 1.9 and 3.7 vol %), as soon as patients reached Stage II and Stage III anesthesia. When fentanyl (MaxDose, 8 micrograms/kg) or nitrous oxide (MaxDose, 79%) was used, the subjects reached Stages I and II, but not Stage III. With these drugs, reliable recording of CMAPs was possible even with the maximal administered dose. PMID- 1738463 TI - Intracerebral schwannoma: case report. AB - A case of intraparenchymal schwannoma is presented. The neuroradiological findings of reported intraparenchymal schwannomas, including the case reported here, are discussed. The specific tumor characteristics are emphasized. This report appears to be the only documentation as a result of magnetic resonance imaging of this specific tumor. PMID- 1738462 TI - Late manifestations of esthesioneuroblastomas in the central nervous system: report of two cases. AB - Two patients with esthesioneuroblastomas that disseminated in the central nervous system (CNS) and elsewhere are reported. The latest recurrences in the CNS were 19 years after the diagnosis in patient and 9 years after the diagnosis in the other. Because the treatment of patients with such late recurrences is complicated by previous surgical procedures and radiation therapy, we review therapeutic options for these patients. The literature has not previously stressed the occurrence of late metastases, including those to the CNS, after prolonged disease-free intervals. PMID- 1738464 TI - Cerebral blood flow correlates of word monitoring in sentences: influence of semantic incoherence. A spect study in normals. AB - The aim of this study was to assess the cerebral blood flow (CBF) changes induced by the semantic incoherence of sentences whose words were to be monitored by the subjects. According to Marslen-Wilson and Tyler, word processing would be parallel (global) in semantically coherent sentences, and serial (local) in semantically incoherent ones. We hypothesized that, in comparison with the parallel mode, the serial mode of word processing would result in a preponderant activation of the frontal lobes and/or of the left hemisphere, hence in a flow increase in these regions. In addition, one could assume that the increase in task complexity resulting from the breaking of semantic coherence would reinforce the functional links between hemispheres. Furthermore, as interactions between the processing of semantically coherent vs incoherent of verbal materials and the processing of imageable vs non-imageable stimuli was recently suspected, we designed a study combining coherent vs incoherent sentences and imageable vs non imageable words. The results we obtained in 12 normal volunteers by measuring regional cerebral blood flow by SPECT and IV injection of Xenon 133 during the four experimental conditions, did not allow us to firmly establish our hypotheses. Indeed, we failed to demonstrate any significant CBF changes across conditions and there was no interaction between coherent vs incoherent and imageable vs non-imageable conditions. However, the analysis of the inter regional correlations pointed to an increase in the functional links between the hemispheres in the incoherent conditions, whatever the imageability. PMID- 1738465 TI - Auditory attention in early Parkinson's disease: an impairment in focused attention. AB - Focused attention in the auditory modality was studied in a group of Parkinson patients and compared to matched controls using a Dichotic monitoring task. Parkinson patients detected more phonemic distractors on the unattended input than the normal controls, despite a high level of ipsilateral responses for target detection and target discrimination. This impairment in focused attention may be attributed to degenerative changes in the ascending monoamine pathways which have been implicated in the role of auditory attention. PMID- 1738466 TI - The measurement of handedness: a cross-cultural comparison of samples from England and Papua New Guinea. AB - Handedness was compared in 125 English children and 185 young people from Papua New Guinea (PNG). Many of the latter were unfamiliar with implements such as pencils and spoons. The PNG subjects showed strong hand preferences, usually for the right, and on some items were more consistent in hand use than the English subjects. However, they had smaller hand differences on peg-moving and tapping than the English children. A factor analysis identified one factor with high loadings from items involving precise motor control, and another with positive loadings from only card-dealing, block-building and threading. The first factor was impervious to cultural influences, whereas the second showed considerable cultural variation. PMID- 1738467 TI - Distributions of hand preference and hand skill asymmetry in preschool children: theoretical implications. AB - We describe the distributions of hand skill asymmetry for the Peg-moving task and the Graphic test among 765 preschool children. A single normal component was observed for the Peg-moving task, but two normal components for the Graphic test, which corresponded primarily to the right- and left-handed children. Hand Preference and Graphic test hand skill asymmetry were age-dependent, but there was no age effect on the PMT hand skill asymmetry. Results are discussed in relation to the Annett's Right Shift theory. PMID- 1738468 TI - Spatial ability as a predictor of math achievement: the importance of sex and handedness patterns. AB - In accordance with major theories of handedness and brain organization, differential predictors for math achievement were found as a function of sex and handedness subgroups among eighth graders. Although there was no difference in absolute levels of performance as a function of either sex or handedness, predictive structures did differ. Regression analyses showed that spatial ability predicts math achievement for: (1) girls with anomalous dominance (non-right handers and right-handers with non-right-handed relatives), and (2) all boys (independent of handedness group). In contrast, for the standard dominance girls who are right-handed with all right-handed relatives (considered strongly left hemisphere dominant for language), spatial ability did not predict for math achievement. These findings occurred, even when scholastic aptitude and verbal achievement factors were controlled. It was concluded that further studies of sex differences in math achievement should consider subgroup differences within the sexes, based on handedness patterns. PMID- 1738469 TI - Hemispheric specialization for skilled perceptual organization by chessmasters. AB - The right cerebral hemisphere may be relatively specialized for parsing simple visual stimuli according to default rules, such as the Gestalt laws of perceptual organization, whereas the left cerebral hemisphere may be relatively specialized for overriding such default rules. We extend this model to 'semantically rich domains' by performing a divided-visual-field experiment on 16 chessmasters. Such subjects are able to recall and recognize complex chess positions by chunking the basic elements of the stimuli--the chess pieces--into meaningful groupings according to certain rules that are specific to the semantic structure of the chess domain. We show that the right hemisphere is superior to the left at parsing according to the default rules of chess chunking, but that the left hemisphere is superior to the right at grouping pieces together in violation of those rules. These results suggest that the right hemisphere is better able to acquire and apply new sets of default parsing rules for specific contexts. We conclude, consistent with other neuropsychological evidence, that the right hemisphere is critical for chess skill. PMID- 1738470 TI - Spatial recognition and spatial order memory in patients with dementia of the Alzheimer's type. AB - Patients diagnosed as having mild or moderate primary degenerative dementia of the Alzheimer's type (PDDAT), and normal elderly subjects were tested for spatial order and a spatial recognition memory. Results for spatial order memory indicated that compared to normal elderly subjects, patients with mild PDDAT showed an impaired memory only for the last serial positions. In contrast, with respect to spatial recognition memory, patients with mild PDDAT showed an impaired memory only for the early serial positions. Patients with moderate PDDAT were impaired on all serial positions for both spatial order and spatial recognition memory. Based on comparable deficit patterns seen in animals and patients with hippocampal and parietal cortex lesions, it is suggested that memory deficits displayed by PDDAT patients might be a function of underlying pathology in the hippocampus and parietal cortex. PMID- 1738471 TI - Impulsivity, risk-taking, and the ability to synthesize fragmented information after frontal lobectomy. AB - Patients with unilateral frontal- or temporal-lobe excisions and control subjects performed a cognitive risk-taking task in which target items (line-drawings or words) had to be guessed on the basis of partial-information clues. For each item, subjects chose to guess with either one, two, three, or all four clues, for a possible reward of 30, 20, 10, or 5 points, respectively. Two clue-presentation conditions were used to allow the differentiation of risk-taking from impulsivity. Whereas no group obtained high risk-taking scores, patients with frontal-lobe lesions demonstrated impulsive behaviour when manual responses were required. Only the left frontal-lobe group was impaired at solving the clues. PMID- 1738472 TI - Reversed laterality of cerebral functions in a non-right-hander: neuropsychological and spect findings in a case of 'atypical' dominance. AB - A 54-year-old non-right-handed man with positive familial sinistrality showed a pure right hemisphere syndrome following a left hemisphere stroke. Severe right side hemineglect, transcortical motor dysprosodia, spatial dysgraphia and visuo constructive impairments were observed. At no time were the expected left hemisphere abnormalities such as aphasia, alexia, right-left disorientation or finger agnosia noted. A left fronto-temporal subcortical lesion was documented on CT scan. A Tc-99m HM-PAO SPECT study revealed no cerebral blood flow changes in the right hemisphere while in the left hemisphere a fronto-temporo-parietal cerebral blood flow reduction was evident. This case of a complete reversed laterality of cognitive functions argues for a distinction to be made between 'anomalous' cerebral dominance and 'atypical' cerebral dominance. PMID- 1738473 TI - The effects of intensity and irrelevant location of a tactile stimulation in a choice reaction time task. AB - Simon and his colleagues have demonstrated that the location of a stimulus in the sensory field, even if it is irrelevant for the task, may critically affect reaction time. This so-called 'Simon effect' is a general phenomenon that encompasses all sensory modalities. The experiment reported here showed that the tactile version of the Simon effect was additive on reaction time with the respective effects of stimulus intensity and of the within-hand/between-hand composition of the repertoire of fingers devoted to the task. In light of recent theoretical developments, the present data suggest that the locus of the Simon effect is stimulus identification, a perceptual stage which follows stimulus encoding and precedes stimulus-response translation. PMID- 1738474 TI - Clustering strategies on tasks of verbal fluency in Parkinson's disease. AB - The verbal output of patients with Parkinson's disease (PD) was analyzed for semantic and phonemic clusters on tasks of verbal fluency. One task required cued retrieval by semantic category (i.e. animals), and one required non-cued retrieval by initial letter (e.g. words beginning with 'F'). Nondemented PD patients (N = 25) produced significantly fewer words on the cued semantic retrieval task than age-, gender- and education-matched normal control subjects (N = 22), but were not impaired on the non-cued letter retrieval task. However, overall, PD patients were able to form more semantic clusters than phonemic clusters. These results are discussed in light of other studies of verbal fluency deficits in patients with PD. PMID- 1738475 TI - Working as an international nurse executive. PMID- 1738476 TI - Nursing administration that is international is broad and outward, not narrow and inward. PMID- 1738477 TI - Challenges to nursing from the World Health Organization and the International Council of Nurses. PMID- 1738478 TI - International nursing administration. PMID- 1738479 TI - Nursing in Malawi: challenges to nurses in leadership positions. PMID- 1738480 TI - King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. PMID- 1738481 TI - Saudi Arabian culture. PMID- 1738482 TI - International nursing recruitment: a personal perspective. PMID- 1738483 TI - Nurse development program. PMID- 1738485 TI - Quality assurance on a roller coaster. PMID- 1738484 TI - Toward effective intercultural teaching. PMID- 1738486 TI - Culturally responsive nursing management in an international health care setting. PMID- 1738487 TI - Educational strategies in a transcultural setting. PMID- 1738488 TI - After war: long-term effects on people, their health, and the health system. PMID- 1738489 TI - Initiating a volunteer program at KFSH. PMID- 1738490 TI - Patient classification in the Groote Schuur Hospital region, Republic of South Africa. PMID- 1738491 TI - Nursing administration trends in Brazil. PMID- 1738492 TI - Health and nursing services in Pakistan: problems and challenges for nurse leaders. PMID- 1738493 TI - Nursing and health services in Austria. PMID- 1738494 TI - Polish nursing in action. PMID- 1738495 TI - Development of nursing services in the Basque Autonomous Region, Spain. PMID- 1738497 TI - Nursing administration in Korea. PMID- 1738496 TI - Nursing in India. PMID- 1738498 TI - Health and nursing services in Cameroon: challenges and demands for nurses in leadership positions. PMID- 1738499 TI - Homing in. PMID- 1738500 TI - Quality of care. PMID- 1738501 TI - Ensuring quality for ostomists. PMID- 1738502 TI - Determining the standards. PMID- 1738503 TI - Accident and emergency audit. PMID- 1738504 TI - A nursing concern. PMID- 1738505 TI - There is a better way. PMID- 1738507 TI - CIS sponsor debate flawed. PMID- 1738506 TI - Publishitis. PMID- 1738508 TI - Renal unit nurses under pressure. PMID- 1738509 TI - Unqualified care. PMID- 1738510 TI - The quest for quality. PMID- 1738511 TI - The Bethesda classification for squamous intraepithelial lesions: histologic, cytologic, and viral correlates. AB - In applying the Bethesda System of classification to cervical squamous lesions, we evaluated the Papanicolaou smears, cervical biopsies, and human papillomavirus (HPV) DNA status of 76 clinic patients. The biopsy specimens and concurrent Papanicolaou smears were analyzed using criteria for low-grade and high-grade squamous intraepithelial lesions, and the biopsies were analyzed for HPV DNA by in situ hybridization. Two independent observers produced good agreement in both cytologic (kappa = 0.62) and histologic (kappa = 0.71) diagnoses. Predictive values of high-grade cytology (for high-grade histology) were high (0.95 for reviewer 1; 0.97 for reviewer 2), and both high-grade cytology and histology correlated strongly with certain "high-risk" HPV types. In contrast, the predictive value of low-grade cytology for either low-grade histology or HPV types other than "high risk" was poor. This study supports the use of certain histologic criteria for distinguishing squamous intraepithelial lesions into two grades. Limitations in cytologic-histologic correlation appear to reflect the absence of cytologic criteria for distinguishing well-differentiated precursor lesions associated with high-risk HPV types. PMID- 1738512 TI - Adenocarcinoma of the cervix treated with radiation alone: prognostic significance of S-100 protein and vimentin immunostaining. AB - Fifty-nine patients with adenocarcinoma of the cervix were treated with radiation alone (eight stage I, 15 stage II, 25 stage III, and 11 stage IV patients). The disease-free 5-year survival rates for each stage were 63, 58, 30, and 9%, respectively. The incidence of vimentin-positive cancer cells in 20 women with adenosquamous carcinoma was significantly higher than that in 34 with endocervical adenocarcinoma (25 versus 6%; P less than .05). The outcome of stage III patients with S-100 protein-positive dendritic cells (Langerhans cells) or without vimentin-positive cancer cells was significantly better than that of women negative for S-100 protein or positive for vimentin (P less than .025 and P less than .05, respectively). These findings indicate that, along with clinical stage, Langerhans cell infiltration and the vimentin negativity of cancer cells are favorable prognostic factors in stage III adenocarcinoma of the cervix treated with radiation alone. PMID- 1738513 TI - The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. AB - To evaluate the relationships between gestational age, neonatal outcome, and amniotic fluid (AF) bacteria, we obtained AF from women with intact membranes in idiopathic preterm labor. Positive cultures were obtained from 20 (19%) of 105 women. The frequency of positive cultures was inversely related to gestational age: 23-26 weeks, nine of 20; 27-30 weeks, four of 24; and 31-34 weeks, seven of 61 (chi2 for trend, P less than .001). Fusobacterium nucleatum, Bacteroides ureolyticus, and Ureaplasma urealyticum were the most common isolates. Facultative and anaerobic bacteria were more commonly isolated from women at less than 30 weeks' gestation, and Ureaplasma urealyticum was commonly isolated at greater than 30 weeks' gestation. Forty percent of the patients identified as having positive AF facultative and anaerobic cultures by the research laboratory had negative cultures in the clinical laboratory. Clinical characteristics and maternal white blood cell count and differential did not differ between women with and without positive cultures. Elevated C-reactive protein levels and a positive AF Gram stain were the two most sensitive and specific methods to predict positive AF cultures. Women with positive cultures delivered a median of 1.0 day after enrollment, compared with 28.5 days for women with negative cultures. The median gestational age at delivery for women with positive cultures was 27.5 weeks, and the median birth weight was 866 g. Positive AF cultures were associated with respiratory distress syndrome, bronchopulmonary dysplasia, and neonatal death. If occult AF infection among women in preterm labor is a treatable cause of preterm birth, then treatment could markedly reduce both perinatal morbidity and mortality. PMID- 1738514 TI - Assessment of a rapid latex agglutination test for group B streptococcal colonization of the genital tract. AB - OBJECTIVE: The purpose of this study was to determine the reliability of a rapid enzyme extraction-latex agglutination test in detecting intrapartum colonization of the maternal genital tract by group B streptococci. METHODS: Swabs of vaginal secretions were obtained from 314 patients in labor with either ruptured or intact membranes. Four tests were performed on each specimen: 1) qualitative culture on blood agar, 2) semiquantitative culture on blood agar, 3) culture in selective Todd-Hewitt broth, and 4) latex agglutination preceded by enzyme extraction. RESULTS: The prevalence of positive cultures was 29%. When compared with culture in Todd-Hewitt broth, the latex agglutination test had a sensitivity of 30%, specificity 93%, positive predictive value 64%, and negative predictive value 76%. In patients with heavy colonization the test had a sensitivity of 76%, compared with 17% in patients with light growth (P less than .001). The lower limit of sensitivity of the test was 4 x 10(5) cfu/mL. The performance of the test was not affected by rupture of the membranes. CONCLUSION: Although the latex agglutination test is reasonably sensitive in detecting heavy colonization, low overall performance combined with technical difficulties in assessment of particle agglutination make the test unsuitable for general screening. PMID- 1738515 TI - Human immunodeficiency virus infection in pregnant women under care at AIDS clinical trials centers in the United States. AB - The federal government supports a nationwide network of medical centers to evaluate promising therapies against the human immunodeficiency virus (HIV) and the opportunistic infections and cancers that characterize AIDS. Forty-five obstetricians from the 49 medical centers receiving federal research support for the conduct of AIDS-related clinical trials, in preparation for a meeting, provided summary information about the number and clinical status of the known HIV-infected pregnant women under their care and the prenatal screening policies for HIV infection at their institutions. In the 12-month period before December 1989, an estimated 1000-1801 HIV-infected women delivered at these centers. The majority (82%) were asymptomatic, 12% were symptomatic, and 6% had AIDS. Routine T-cell testing of infected women was done as part of prenatal care in only 30 of 45 centers. Pneumocystis carinii pneumonia was reported in 35 women. Zidovudine was administered during pregnancy in 29 women. Formal prenatal screening policies have been implemented at the majority (43 of 45) of the medical centers. Most of the infected women identified at these centers chose to continue the pregnancy. With the increasing incidence of HIV infection in women, information concerning the clinical and immunologic state of pregnant infected women and the present use of antiretroviral and other related therapeutics during pregnancy can guide the approach to women's health care and is crucial to the design and implementation of AIDS clinical trials. PMID- 1738516 TI - The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women. AB - Lactobacilli provide an important microbial defense against genital colonization by pathogens. The role of hydrogen peroxide (H2O2) in the control of genital microflora was explored in a cross-sectional study of 275 women in the second trimester of pregnancy. Vaginal cultures were obtained for detection of H2O2 positive and H2O2-negative lactobacilli and other members of the genital microflora. Compared with women with H2O2-negative lactobacilli, women colonized by H2O2-positive lactobacilli were less likely to have bacterial vaginosis, symptomatic candidiasis, and vaginal colonization by Gardnerella vaginalis, Bacteroides, Peptostreptococcus, Mycoplasma hominis, Ureaplasma urealyticum, and viridans streptococci (P less than or equal to .05 for each comparison). In addition to the above organisms, women without vaginal lactobacilli were more likely than those women with H2O2-positive lactobacilli to have Chlamydia trachomatis, and less likely to be colonized by Enterococcus or coagulase negative staphylococci (P less than .05 for each comparison). Vaginal colonization by group B streptococci or Escherichia coli was not related to the presence of H2O2-positive lactobacilli. These data suggest that the presence of H2O2-positive lactobacilli in the vagina is inversely correlated with infection by some genital pathogens in pregnant women. PMID- 1738517 TI - An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term. AB - The purpose of this randomized, double-blind study was to evaluate the efficacy and safety of a new controlled-release hydrogel pessary for ripening the cervix and initiating labor. Subjects had an entry Bishop score of 4 or less and gestational age of 37 or more weeks. One hundred fourteen women received a placebo pessary and 101 received the hydrogel pessary, containing 10 mg of prostaglandin (PG) E2. Compared with the placebo group, those given the PGE2 pessary were more likely to have an increase in Bishop score of 3 or more (60 or 59% versus 21 or 18%; P less than .0001), change to a Bishop score of 6 or higher (59 or 58% versus 18 or 16%; P less than .0001), and active labor (68 or 67% versus 15 or 13%; P less than .0001). Including the crossover study, uterine hyperstimulation (28 of 182, 15%) and fetal heart rate abnormalities (18 of 182, 10%) in PGE2-treated subjects were reversed on removal of the pessary with no apparent harm to the mother or fetus. These temporary adverse effects appeared while the pessary was in place and after the onset of active labor. Oxytocin was unnecessary in 89 of 182 (49%) of the PGE2-treated cases and was used more often to augment than to induce labor. We conclude that the described controlled release PGE2 vaginal pessary induces appreciable cervical ripening and frequently initiates active labor with little or no need for oxytocin. The pessary may cause uterine hyperstimulation or fetal heart rate abnormalities, but these would be expected to reverse on removal of the pessary. PMID- 1738518 TI - Maternal transport of patients with advanced cervical dilatation--to fly or not to fly? AB - Emergency maternal transport of women in advanced preterm labor often involves difficult decisions about whether to transport or not. A retrospective review of maternal transports performed in northern Arizona by Samaritan Air Evac covered a 21-month period. Of the 1080 patients transported for preterm labor, 54 calls for transport (5%) were received when the patient was 7 cm or more dilated. Five women were delivered at the referring hospital and 49 were transported, none of whom delivered en route. Only 21 (39%) of them delivered in the first hour after arrival at the tertiary center. The decision to transport patients in advanced preterm labor should be based on such factors as distance between hospitals, time required to cover that distance, personnel on the transport, facilities available at the transporting hospital, gestational age, and speed with which labor has progressed. PMID- 1738519 TI - Fetomaternal hemorrhage in threatened abortion. AB - In this study, we compared the incidence of fetomaternal hemorrhage between patients with threatened abortion and a control population of similar gestational age. The study population comprised pregnant patients at less than 20 weeks' gestation who presented to our emergency room with a history of vaginal bleeding without cervical dilatation or passage of tissue. The control population consisted of women presenting for elective pregnancy termination; they were excluded from the study if they gave a history of any antepartum bleeding. The amount of fetomaternal hemorrhage was evaluated using the Kleihauer-Betke acid elution assay. A positive result in our laboratory, as determined by a nonpregnant control group, was a value of 0.07% or more fetal cells. Using this criterion, 11% of the study population had a positive Kleihauer-Betke test, compared with 4% in the pregnant control group. Rho(D) immunoglobulin may be indicated in Rho(D)-negative patients who present with threatened abortion. PMID- 1738520 TI - Relation of mild idiopathic polyhydramnios to perinatal outcome. AB - The relation between clinically obvious polyhydramnios and poor perinatal outcome has been described. Much less is known about mild, unexplained polyhydramnios, which usually is initially suggested by sonographic examination late in gestation. The purpose of the present investigation was to relate mild idiopathic polyhydramnios to perinatal outcome. Mild polyhydramnios was defined sonographically as an amniotic fluid index of 24.1-39.9 during fetal biophysical testing. All subjects had singleton gestations not complicated by conditions known to predispose to polyhydramnios. We diagnosed mild polyhydramnios in 97 of 1177 patients (8.2%) undergoing fetal testing at 26-42 gestational weeks. Premature delivery, intrapartum complications, and neonatal depression were no more frequent in the pregnancies complicated by mild, unexplained polyhydramnios than in a comparable control group with normal fluid volume. The mild polyhydramnios group showed a significantly higher incidence of birth weight greater than 4000 g than did the control group (18.6 versus 8.6%; P less than .05). We conclude that mild idiopathic polyhydramnios in late gestation is relatively common. Except for a higher incidence of large for gestational age fetuses, this condition by itself is not associated with an increased risk of adverse perinatal outcomes. PMID- 1738521 TI - The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death. AB - Hydrops caused by isoimmune hemolytic anemia is frequently associated with fetal death following intrauterine intravascular transfusion. To identify possible predictors of procedure-related fetal death, we examined changes in fetal blood volume and hematocrit resulting from the initial transfusion performed on 19 severely anemic, hydropic fetuses. Seven fetuses (36.8%) died at 24-72 hours after transfusion, but in no case was the procedure associated with fetal distress. There were no significant differences between fetuses who died and those who survived in terms of total volume of blood transfused, volume transfused as a percentage of total fetoplacental blood volume, hematocrit of transfused blood, post-transfusion hematocrit, umbilical vein pH, or gestational age at transfusion. Significant differences were noted between hydropic fetuses who died compared with those who survived in the mean pretransfusion hematocrit, 6.7% (+/- 2.0) versus 8.7% (+/- 1.6) (P = .03), and the relative increase in post over pre-transfusion hematocrit, 5.5-fold (+/- 1.4) versus 3.5-fold (+/- 0.8) (P = .001). Stepwise logistic regression analysis confirmed that only the relative increase in hematocrit was predictive of fetal loss. Moreover, six of seven fetal deaths occurred when the relative increase in hematocrit was greater than fourfold, whereas ten of 12 surviving fetuses had relative increases of less than fourfold. We conclude that large, acute increases in fetal hematocrit following intrauterine transfusion are associated with substantial mortality in hydropic fetuses. PMID- 1738522 TI - Comparison of cord purine metabolites to maternal and neonatal variables of hypoxia. AB - Umbilical arterial concentrations of purine metabolites were evaluated prospectively as markers of hypoxia. The results suggest that hypoxanthine accumulates in association with fetal acidosis and reduced levels of buffer base (P less than .01). Acute hypoxemia defined by umbilical arterial oxygen pressure was accompanied by elevation of uric acid concentrations (P less than .01). Fetal heart rate tracings with characteristics classically associated with fetal stress correlated with increased concentrations of hypoxanthine and xanthine (P less than .01). Therefore, intrapartum events may occur that are not documented by standard markers of perinatal hypoxia at delivery. PMID- 1738523 TI - Placental compressibility: implications for indirect diagnosis of posterior placenta previa. AB - A number of problems beset the indirect diagnosis of posterior placenta previa using transabdominal ultrasound. We add a new potential complicating factor. In 128 pregnancies at or beyond 30 weeks' gestation, measurements were taken from the fetal skull to the maternal sacrum before and after compression. Up to 69% compressibility of the placenta was found in vivo and in vitro. Modified fetal skull to maternal sacrum measurement criteria were devised from the results. Placenta previa is highly unlikely if the measurement from the fetal skull to maternal sacrum is less than 10 mm before compression or less than 7 mm after compression. Placenta previa is probable if the measurement is greater than 20 mm before compression or greater than 15 mm after compression. In 40% of the cases, posterior placenta previa could not be excluded. We conclude that placental compressibility is an additional confounding problem for indirect ultrasound assessment of posterior placenta previa and that indirect assessment should be attempted only if maneuvers to image the lower uterine segment directly are unsuccessful. PMID- 1738524 TI - Endothelin transfer and endothelin effects on water transfer in human fetal membranes. AB - Although endothelin-1 is synthesized by human amnion, its physiologic role and its ability to be transferred to myometrium for oxytocic action remain unclear. We investigated the transfer of endothelin-1 itself and the effects of endothelin 1 on the transfer of tritiated water across human amnion or amnion/chorion/decidua in vitro with an Ussing chamber technique. Permeability coefficients (mean +/- standard error) for 3H2O across amnion/chorion/decidua in the fetal to maternal direction were 1.26 +/- 0.21 and 1.25 +/- 0.10 x 10(-4) cm/second (N = 6) and in the maternal to fetal direction 0.90 +/- 0.07 and 0.98 +/- 0.15 x 10(-4) cm/second (N = 5) in the absence or presence, respectively, of 10(-9) mol/L endothelin-1 in the fetal reservoir. Comparable values were found in either direction with 10(-9) mol/L endothelin-1 in the maternal reservoir. Apparent permeability coefficients for 125I endothelin-1 in the fetal to maternal direction were 3.34 +/- 0.79 and 2.43 +/- 0.68 x 10(-5) cm/second (N = 5) for amnion or amnion/chorion/decidua. However, appreciable trapping of 125I endothelin-1 by the fetal membranes was apparent. Endothelin-1 does not appear to affect water movement across the human fetal membranes, and only a small proportion of endothelin-1 itself is transferred across the membranes. PMID- 1738525 TI - Cerebral-umbilical Doppler ratio as a predictor of adverse perinatal outcome. AB - Using a 3.5-MHz duplex Doppler system, 45 normal-growth and 45 growth-retarded fetuses were studied between 30-41 weeks' gestation. Velocity recordings were obtained from the middle cerebral artery and umbilical artery to calculate the ratio between the two pulsatility indexes. The cerebral-umbilical Doppler ratio is usually constant during the last 10 weeks of gestation. Therefore, a single cutoff value (1.08) was used, above which velocimetry was considered normal and below which it was considered abnormal. The cerebral-umbilical Doppler ratio provided a better predictor of small for gestational age newborns and adverse perinatal outcome than either the middle cerebral artery or umbilical artery alone. In fact, in predicting those newborns who were small for gestational age, the cerebral-umbilical ratio had a 70% diagnostic accuracy [(true positive + true negative)/total number of cases], compared with 54.4% for the middle cerebral artery and 65.5% for the umbilical artery. The results were more encouraging for prediction of adverse perinatal outcome; diagnostic accuracy for the cerebral umbilical ratio was 90%, compared with 78.8% for the middle cerebral artery and 83.3% for the umbilical artery. PMID- 1738526 TI - Selected intrapartum external cephalic version of the second twin. AB - After delivery of twin A, external cephalic version was attempted on 30 malpositioned second twins (12 transverse and 18 breech). Version was successful and resulted in subsequent vertex vaginal delivery for 11 of the 12 transverse presentations and 16 of 18 breech presentations. Successful version was not associated with parity or with birth weight. Among the 30 attempted versions, only one infant had a 1-minute Apgar score below 7. There were not enough cases to determine an association of delivery interval between twins and poor neonatal outcome. External cephalic version in selected twin gestations is useful for management of the second twin with abnormal presentation. Technique refinement and greater experience may improve the overall success rate with external version of the second twin. Although external cephalic version cannot yet be recommended as the method of choice, the procedure seems safe, and routine cesarean delivery may not always be indicated. PMID- 1738527 TI - Factors that influence weight loss in the puerperium. AB - A study group of 795 women was followed with frequent weight measurements and questionnaires about their activities for 6 months postpartum. The mean (+/- SD) net weight gain from the first prenatal visit to 6 months postpartum was 1.4 +/- 4.8 kg. Weight gain during prenatal care was the variable most highly correlated to weight loss. Return to work outside the home, parity, and smoking also correlated significantly to weight loss. Breast-feeding, exercise, season of the year, age, and marital status were not correlated. Route of delivery was related to weight loss at 2 and 6 weeks, but not at 6 months. Counseling women about weight gain during pregnancy and weight loss requires an understanding of these variables with a long-term perspective of at least 6 months. PMID- 1738528 TI - Oral contraceptive use and risk of uterine fibroids. AB - The association between oral contraceptive (OC) use and the risk of uterine fibroids was analyzed in a case-control study conducted between 1986-1990. The subjects were 390 patients under 55 years of age with histologically confirmed fibroids and 1136 controls in hospitals for a spectrum of acute conditions (other than gynecologic, hormonal, or neoplastic) apparently unrelated to OC use. A total of 78 cases (20%) and 200 controls (18%) reported OC use. Compared with never-users, the multivariate relative risk for ever-users was 1.1 (95% confidence interval [CI] 0.8-1.5). No direct relationship emerged with duration of use, the estimated relative risk being 1.3 (95% CI 0.9-2.0) in users of OCs for less than 3 years and 0.8 (95% CI 0.5-1.3) in users for 3 years or more. The risk of fibroids was apparently (though not significantly) greater with longer recency of use: The estimated relative risks were 0.9 and 1.5, respectively, in women reporting last OC use less than 10 years before and 10 or more years before diagnosis of the disease. No relationship emerged with latency of use. There was no noteworthy interaction regarding risk of fibroids between OC use and potential covariates. These findings suggest that fibroids are unrelated to the use of OCs. PMID- 1738529 TI - Treatment options for human immunodeficiency virus-infected pregnant women. Obstetric-Gynecologic Working Group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. AB - The increasing seroprevalence of human immunodeficiency virus (HIV) among women of reproductive age and the risks of vertical transmission of HIV have led to recommendations for routine prenatal HIV counseling and testing. The incentive to undergo such testing is related not only to fetal concerns, but also to the potential benefit of early and comprehensive therapy for women. Treatments that should be considered for use during pregnancy include the antiretroviral agent zidovudine and prophylactic agents to prevent Pneumocystis carinii pneumonia, the most common opportunistic infection seen in patients progressing to AIDS. Assessment of the risks and benefits of these treatments during pregnancy is complex and requires discussions between physician and patient. This paper reviews current information and provides recommendations for incorporating therapies into obstetric practice. PMID- 1738530 TI - Transvaginal mobilization and utilization of the anterior bladder wall to repair vesicovaginal fistulas involving the urethra. AB - Repair of vesicovaginal fistulas resulting from obstetric trauma remains a major challenge to surgeons worldwide. Large defects that result in partial or total urethral loss are especially difficult to repair. Even when closure of such fistulas is accomplished, return of normal urogenital function is often impaired, underscoring the need to improve existing surgical procedures. Transvaginal urethral and bladder neck reconstruction using mobilized anterior bladder wall was helpful in closing 18 of 20 vesicovaginal fistulas with urethral involvement caused by obstetric trauma. This method involves advancement of an anterior bladder wall flap into the vagina, where it is rolled into a neo-urethra or connected to whatever remnant of urethral tissue exists. Complications included stress incontinence requiring further surgery (four), small bladder capacity with detrusor instability (two), urethral stenosis requiring dilatation (two), postoperative hemorrhage (one), and vaginal stenosis (one). Continued modification of this procedure holds promise for many patients considered inoperable in the past. PMID- 1738531 TI - The utility of the TDx test in the assessment of fetal lung maturity. AB - Accurate assessment of fetal lung maturity is essential in the management of high risk obstetric patients. New rapid techniques have been developed to supplement time-consuming chromatographic methods. We compared one of these newer methods, the TDx-FLM, to the standard tests for fetal pulmonary maturity. There was an excellent correlation between the TDx and the lecithin-sphingomyelin ratio (r = 0.78). Although a TDx value of 70 or greater is considered mature, we found a value of 50 or greater predictive of fetal lung maturity in 100% of cases, and have chosen to redefine a mature value as 50 or greater in our institution. This value has greatly enhanced the clinical applicability of the test, allowing use of a large number of specimens from the previously poorly understood and often disregarded borderline category. PMID- 1738532 TI - Continuous monitoring of fetal temperature by noninvasive probe and its relationship to maternal temperature, fetal heart rate, and cord arterial oxygen and pH. AB - The human fetus is normally warmer than its mother. The principal route of fetal heat dissipation is through the placental circulation. We developed a technique that is noninvasive to the fetus to record the fetal skin and maternal uterine wall temperatures, from which we derived the temperature difference. We have established a range of normal values (mean temperature difference 0.24C) and present some preliminary data. The results show a correlation between changing temperature and baseline fetal heart rate (r = 0.628, P less than .001) and the influence of contractions and epidural analgesia on these measurements. Measurement of the fetal-maternal temperature difference during labor may help detect abnormal umbilical-placental blood flow, resulting in fetal distress, and may help distinguish sinister from iatrogenic fetal tachycardias. Our technique provides the first simple means of recording this basic fetal variable. PMID- 1738533 TI - Diagnosis and management of chronic hypertension in pregnancy. PMID- 1738534 TI - Court-ordered treatment in obstetrics: the ethical views and legal framework. PMID- 1738535 TI - Court-ordered treatment in obstetrics: the ethical views and legal framework. PMID- 1738536 TI - [Burnout or daily motivation]. PMID- 1738537 TI - [Nursing: profession or calling? A transition from "nursing as a calling" to "nursing as a profession" is necessary and in the end it is up to us nurses to give to our profession a direction, satisfactory to ourselves]. PMID- 1738538 TI - [Expectations and reality in nursing]. PMID- 1738539 TI - [Strategies for the enhancement of motivation. Motivation--the key to success?]. PMID- 1738540 TI - [Nursing diploma--the beginning or the end?]. PMID- 1738541 TI - [Position of the Austrian Nurses Federation towards the article: Socialminister Hesoun is looking for 2500 nurses]. PMID- 1738542 TI - Prevalence of post-headshake nystagmus in patients with caloric deficits and vertigo. AB - Post-headshake nystagmus (PHN) has recently been described as a clinically useful physical sign implying uncompensated asymmetric input from the vestibular end organs. A rapid 20-second headshake and sudden stop produces a jerk nystagmus of 5- to 20-second duration in certain individuals with symptoms suggestive of a peripheral vestibulopathy. This retrospective review of 214 patient evaluations was undertaken to study the associations between post-headshake nystagmus, caloric deficits after bithermal binaural irrigation, and the presence of vertigo. Both clinical observation of the nystagmus with eyes open (PHN-OBS) and routine EOG recording with eyes closed (PHN-EOG) were used. In patients with unilateral caloric deficits, 42% (18 of 43) had PHN-EOG, compared with 18% (3 of 17) in patients with bilateral dysfunction and 15% (23 of 154) in patients with normal calorics (p less than 0.001). In similar fashion, 26% (32 of 124) of patients with vertigo (recent or past) had PHN-EOG compared to 13% (12 of 90) of patients without vertigo (p less than 0.03). Finally, of 110 cases with both PHN EOG and PHN-OBS performed, 45% (9 of 20) with PHN-EOG also had PHN-OBS, as opposed to only 4% (4 of 90) without PHN-EOG displaying PHN-OBS (p less than 0.0001). We conclude that the prevalence of post-headshake nystagmus is increased in patients with either a unilateral caloric deficit or a history of true vertigo, and is best detected in the absence of vision. PMID- 1738543 TI - Meningiomas of the jugular foramen. AB - Meningiomas of the jugular foramen manifest the same signs and symptoms as glomus jugulare tumors. They arise from arachnoid cells lining the jugular bulb and grow slowly, infiltrating the temporal bone and posterior fossa. These lesions, however, are more clinically treacherous than glomus tumors. Meningiomas infiltrate surrounding bone and nerve tissue and require wide margins of resection to prevent recurrence. Eight of these lesions have been managed in the past 5 years at the House Ear Clinic using modern imaging and skull base techniques. Two have recurred after "total" microsurgical removal. Presentation, radiologic evaluation, and management guidelines are reviewed. PMID- 1738544 TI - The efficacy of perioperative antibiotic therapy on recovery following tonsillectomy in adults: randomized double-blind placebo-controlled trial. AB - One hundred and one adult patients undergoing tonsillectomy for chronic/recurrent tonsillitis completed a prospective, randomized, double-blind, placebo-controlled study in which ticarcillin disodium and clavulanate potassium (Timentin) or placebo was administered intravenously at the time of surgery and for 12 hours postoperatively. The patients than received oral amoxicillin and clavulanate potassium (Augmentin) therapy or placebo for an additional seven days. Each patient kept a daily log to assess the incidence and severity of postoperative symptoms. Tonsillar core tissue at the time of surgery, as well as tonsillar fossa cultures after 7 days of treatment, were obtained. Those patients who received antibiotics fared consistently better in the immediate postoperative period compared with the placebo group. Specifically, patients in the antibiotic group experienced significantly less mouth odor, were able to tolerate a regular diet sooner, and resumed their normal activities earlier than did patients who received placebo. Patients who received antibiotics experienced fewer days with mouth odor (p = 0.004). In addition, on postoperative days 3 to 5, the antibiotic group was eating a regular diet (p = 0.05) and had returned to their routine activities earlier (p = 0.045) when compared with the placebo group. Perioperative antibiotic therapy was well tolerated and was effective in minimizing symptoms after tonsillectomy. PMID- 1738545 TI - Airway changes in relationship to mandibular posturing. AB - Comparison of posterior airway space was evaluated radiographically on patients with sleep apnea in a mandibular reposed position vs. a mandibular protruded position. This was performed at the Santa Barbara Sleep Disorders Medical Center to simulate the effect of anterior orthotic appliances on these patients. The overall effect of forward mandibular posturing was a mean increase of posterior airway space (PAS) by approximately 56%, but wide variations were seen. PMID- 1738546 TI - Head and neck squamous cell carcinoma cell line-induced suppression of in vitro lymphocyte proliferative responses. AB - Tumour-infiltrating lymphocytes (TILs) are often difficult to expand in vitro. In some cases this has been attributable to immunosuppression mediated by the elaboration of prostaglandins by either tumor cells or tumor-infiltrating monocytes. In this laboratory, freshly prepared TILs containing single-cell suspensions of head and neck tumors displayed both poor proliferation as well as minimal responsiveness to indomethacin-mediated reversal of immunosuppression. In order to investigate tumor-mediated immunosuppression further, a system was developed whereby a new cell line of head and neck squamous cell carcinoma was used to suppress allogeneic peripheral blood mononuclear cell proliferation in response to phytohemagglutinin (PHA) and Interleukin-2 (IL-2). Tumor cells were able to suppress peripheral blood mononuclear cell (PBMNC) proliferation up to 95%. This suppressive effect was dependent on tumor cell number and was reversible by the use of higher concentrations of PHA, but not by increased concentrations of IL-2. Suppression was immediate when IL-2 was used as the stimulus for proliferation, but required extended lymphocyte/tumor cell contact when PHA was used. Flow cytometric analysis of tumor-exposed and PHA-stimulated PBMNCs revealed a decrease in both the number of cells expressing IL-2 receptors as well as the density of IL-2 receptors per cell. This pattern of suppression, as well as the reversibility of suppression by indomethacin, implicates prostaglandins in the mechanisms by which these tumor cells mediate immunosuppression. PMID- 1738547 TI - Basaloid-squamous carcinoma of the palate. AB - Basaloid-squamous carcinoma is a rare, nonsquamous cell tumor presenting in the head and neck that has recently been described. The clinical and histopathologic features of basaloid-squamous carcinoma derived from the 12 reported cases in the literature, including our case resembling an arteriovenous malformation, are described. The important interaction of the operating surgeon with the surgical pathologist in guiding the extent of the resection is emphasized. PMID- 1738548 TI - Cricopharyngeal dysfunction. AB - The aim of the study was to determine the manometric patterns in dysphagic patients with radiologic evidence of upper esophageal sphincter (UES) dysfunction. Nineteen patients with radiographic abnormalities of the UES underwent measurement of several parameters of UES tonic pressure and pharyngoesophageal water swallow dynamics. At least two UES tonic pressures were elevated in six subjects, compared with a control group of 67 healthy volunteers. No patients had UES achalasia. The cricopharyngeal impression in the remaining patients may represent muscular hypertrophy or deficiency of UES opening, despite manometric relaxation, but its relationship to the patient's symptoms remains unknown. Cricopharyngeal myotomy appears to be a reasonable treatment for patients with manometric UES hypertonicity. PMID- 1738549 TI - The effects of bolus flow on vertical pharyngeal pressure measurement in the pharyngoesophageal segment: clinical significance. AB - Measurement of pressures in the pharyngeal esophageal segment (P-E segment) is complicated by the vertical motion and by the rapidly changing pressures in the segment. The sensors move superiorly and inferiorly with respect to the P-E segment during the swallow. This study examines the validity of manofluorographic measurements taken in the P-E segment by using a catheter with sensors spaced at 1 cm intervals. Seven normal volunteers were tested. Measurements were similar using one sensor and using an average of five sensors. During the time of bolus passage, the P-E segment is open and the bolus itself equalizes pressures measured within the bolus. PMID- 1738550 TI - Effects of vestibular rehabilitation on dizziness and imbalance. AB - Vestibular rehabilitation is a specific approach to physical therapy aimed at reducing dizziness and imbalance by facilitating central nervous system compensation for peripheral vestibular dysfunction. This article reports preliminary results of studies concerning the relative effectiveness of vestibular rehabilitation, general conditioning exercises, and vestibular suppressant medication on dizziness and imbalance in patients with chronic vestibular symptoms of at least 6 months duration. Patients with positional and/or movement-related dizziness and abnormal posturography were randomly assigned to the three treatment groups. Preliminary results suggest that although all three treatment approaches reduce dizziness, only vestibular rehabilitation also improves balance. This study takes the first step toward determining the efficacy of a specific exercise approach for reducing dizziness and imbalance in patients with chronic peripheral vestibular disorders. PMID- 1738551 TI - Characterization of the immune barrier in human olfactory mucosa. AB - Immunologic defense factors in the human olfactory mucosa were localized immunohistochemically. Olfactory epithelium was identified with an antiserum to olfactory marker protein, specific for olfactory receptor neurons. Constituents of the secretory immune system, including IgA, IgM, secretory component, and J chain, were localized in the acinar and duct cells of Bowman's glands and in the mucociliary complex. In addition, B lymphocytes in the lamina propria near Bowman's glands displayed immunoreactivity for IgA, IgM, and J chain. Immunostaining also localized other humoral factors. Immunoreactivity for IgG was present throughout the stroma and in B lymphocytes in the lamina propria. Antibody to IgD stained numerous B lymphocytes clustered below the basement membrane. Antibody to IgE stained similarly distributed cells; toluidine blue staining demonstrated that many were mast cells. In addition, antibodies to IgD and IgE stained occasional intraepithelial B lymphocytes or mast cells. Two antimicrobial proteins, lactoferrin and lysozyme, were localized in Bowman's glands and the mucociliary complex. Thus, the human olfactory mucosa, which provides a direct neural route for pathogens to the brain, is a site for synthesis and secretion of immune and other defense factors. PMID- 1738552 TI - Complications of secondary tracheoesophageal puncture: the Cleveland Clinic Foundation experience. AB - One hundred forty-six secondary tracheoesophageal puncture (TEP) procedures were performed on 132 patients at the Cleveland Clinic Foundation in the past 10 years. The complications of these procedures are reviewed, along with assessment of potential risk factors such as irradiation, esophageal/hypopharyngeal stricture, alcoholism, diabetes, or chronic obstructive pulmonary disease. Among the subgroups studied, only stricture dilation was associated with an increased incidence of postsurgical complications. The majority of these, however, were immediate, and were probably related to the esophagoscopy or dilation itself. The incidence of TEP-related complications in all groups of patients may be higher than previously suspected. PMID- 1738553 TI - Ventilation tubes and prophylactic antibiotic eardrops. AB - Insertion of ventilation tubes has successfully remedied chronic otitis media with effusion in millions of children, but the procedure has been complicated by secondary infections and otorrhea in as many as 34% of the cases. Because infection at the time of surgery was suspected as the primary cause of these postoperative complications, short-term prophylaxis with antibiotic eardrops was proposed for averting secondary infections. To evaluate this hypothesis, we conducted a 6-month prospective study in which 200 children had bilateral tube insertions. Antibiotic eardrops were administered to patients' right ears intraoperatively and for 3 days after surgery; left ears received no eardrops and served as controls. The prophylactic strategy did not significantly decrease the incidence of postoperative otorrhea in treated right ears compared with controls. PMID- 1738554 TI - Immunohistochemical analysis of otic capsule osteogenesis in the Palmerston North autoimmune mouse. AB - Autoimmunity and the immune complex disease associated with it have been hypothesized to be the cause of several idiopathic diseases of the inner ear- including the new bone formation associated with otic capsule osteogenesis and otosclerosis. The Palmerston North (PN) autoimmune mouse strain, which exhibits both spontaneous systemic autoimmune disease and otic capsule bone formation, has been proposed as a model relating these two disease processes. To investigate the potential role of immunopathologic processes in PN otic capsule lesion formation, inner ears from PN mice were immunostained for the presence of IgG and complement (C3), two immunologic markers involved in the development of the vascular and perivascular changes associated with immune complex deposition. Both systemic autoimmune disease and otic capsule bony lesions were confirmed in all animals. However, immunohistochemical analyses did not establish a direct relationship between the two conditions as complement was absent in all lesions and IgG stained positive in only one instance. These results suggest that immune complex deposition is not directly involved in the otic capsule lesions of the PN mouse, and alternate mechanisms relating autoimmune disease and otic capsule osteogenesis must be explored. PMID- 1738555 TI - Parosteal osteosarcoma. PMID- 1738556 TI - Neuroleptic malignant syndrome during perphenazine treatment in a patient with head and neck cancer: a case report. PMID- 1738557 TI - Two unusual locations of osteoradionecrosis. PMID- 1738558 TI - Pinnochio travels to Oz. PMID- 1738560 TI - RBRVS enactment prompts new E/M codes. PMID- 1738559 TI - Legislative grand rounds: 1991. PMID- 1738561 TI - An open letter to Magic Johnson. AB - The last installment in this series dealt with post-test counseling of a person whose HIV test was negative. The plan was to provide counseling for an HIV infected person in this installment. NBA basketball star Magic Johnson's surprise announcement on November 7, 1991, of his infection with HIV has provided an unexpected opportunity to counsel a well-known person through an "open letter." PMID- 1738562 TI - State Medical Board considering HIV/HBV policy. PMID- 1738563 TI - Recouping past-due charges. The Health Care Group. PMID- 1738564 TI - Grappling with managed care: where does medical education fit? AB - While the effects of managed care on access and quality have been extensively debated, the implications of these efforts on medical education have not been widely explored. Because managed care will increasingly impact upon medical education, now is an opportune time to examine its effect and to discuss the need for medical students to be aware of managed care principles. PMID- 1738565 TI - Learning generics. AB - The growing use of generic drug substitution may have important implications on quality of care. This study was conducted to determine resident physicians' knowledge of restrictive prescribing policies at the hospitals where they primarily practice. PMID- 1738567 TI - No quick-fix solutions for medicine. PMID- 1738566 TI - Update: Medicare patient records in physicians' offices. AB - We have become aware of a growing concern among physicians who are under the impression that review of Medicare patients' records in physicians' offices is imminent. Our current activity of reviewing care provided by health maintenance organizations (HMOs) may have caused some physicians to believe that such review had already started. HMO review may, at times, include a request for office records, but such requests are made to the HMO. The review does not take place at the physician's office. PMID- 1738568 TI - The primate dorsal spinothalamic tract: evidence for a specific termination in the posterior nuclei (Po/SG) of the thalamus. AB - The spinothalamic tract in primates and other mammals arises primarily from cells in lamina I of the dorsal horn, from lamina V cells and to a lesser extent from other laminae. Most of the neurons of lamina I respond only to noxious mechanical or thermal stimuli. Spinothalamic tract (STT) cells of lamina V tend to respond to both innocuous and noxious stimuli. Recent studies have suggested that the classical STT in the anterolateral quadrant (ALQ) contains primarily the axons of lamina V cells and that the axons of lamina I cells travel more dorsally in the dorsolateral quadrant (DLQ) to constitute the dorsal spinothalamic tract (DSTT). Using the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) injected into the spinal cord in conjunction with a contralateral anterolateral cordotomy, we have found there is a substantial projection of the DSTT to the posterior nuclei of the caudal-ventral thalamus, designated Po/SG. This projection is almost entirely abolished when the lesion includes the area of spinal cord white matter at the level of the denticulate ligament. Larger lesions that destroy the ALQ and much of the lateral column white matter, but that spare the dorsolateral column white matter in the region of the corticospinal tract, abolish all transport of WGA-HRP to the thalamus. We conclude that the spinothalamic pathway in the non-human primate encompasses a continuous fiber bundle that extends dorsally to include the region of lateral column white matter opposite the denticulate ligament and that the more dorsal aspect of this pathway projects primarily to Po/SG of thalamus. PMID- 1738569 TI - Morphine blocks descending pain inhibitory controls in humans. AB - In man, heterotopic painful thermal conditioning stimuli induce parallel decreases in the spinal nociceptive flexion (RIII) reflex and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve at the ankle. Such phenomena may be related to the diffuse noxious inhibitory controls (DNIC) which were initially described in the rat and subsequently documented in humans. In 9 subjects in the present study, a 2 min application of a moderately noxious temperature (46 degrees C) to the contralateral hand strongly depressed the RIII reflex elicited in the biceps femoris muscle by electrical stimulation of the sural nerve at 1.2 times the reflex threshold. These depressive effects were maximal during the second min of the conditioning period, showing a 80% inhibition of the RIII reflex which gradually recovered to its baseline value 7 min after the end of the conditioning period. Such inhibitory effects were completely blocked 15-26 min after administration of a low dose of morphine hydrochloride (0.05 mg/kg, i.v.). The lifting of the inhibitions was compatible with an action at the opioid receptors since the inhibitions were re-observed 5 16 min after naloxone injection (0.006 mg/kg, i.v.). During all the experimental sessions, heart and respiratory rates remained stable at their control levels. Since it has been shown previously that such a dose of morphine could not have a direct effect within the spinal cord (Willer 1985), it is concluded that this opiate blocks, in a naloxone-reversible fashion, those bulbo-spinal controls which are triggered by heterotopic nociceptive events. Possible implications for hypoalgesia based on the principles of counter-irritation are discussed. PMID- 1738570 TI - Calcitonin in phantom limb pain: a double-blind study. AB - Salmon calcitonin (s-CT) has been shown to be a valuable analgesic in phantom limb pain (PLP) in several case reports. To evaluate these findings a double blind crossover comparison of s-CT treatment versus placebo was initiated. Twenty one out of 161 patients who had undergone major amputations and developed severe PLP 0-7 days after surgery were included in the study. For each patient a matched pair of infusions was prepared containing either 200 IU of s-CT or placebo. Group I (n = 11) was first given s-CT and group II (n = 10) placebo. When PLP reached a level of more than 3 on a numeric analogue scale (NAS) the first infusion was administered. The second infusion (crossover) or more infusions were given when the pain level again exceeded more than 3 on NAS. Using s-CT infusion, PLP was eased from a median of 7 to 4 on NAS in both groups (P less than 0.001), regardless of whether s-CT or placebo was given first. Placebo, however, did not change pain scores (median 7 on NAS, P greater than 0.1). In the s-CT group, but not in the placebo group, 4 individuals remained pain free without a second infusion. Any further treatment was performed with s-CT. One week after the first PLP treatment 19 patients (90%) had pain relief of more than 50%, 16 (76%) were completely pain free, and 15 (71%) never experienced PLP again. One year later 8 out of the 13 surviving patients (62%) still had more than 75% PLP relief. After 2 years PLP exceeded 3 on NAS in 5 individuals (42%), and the remaining 12 patients presented the same PLP as after 1 year. In conclusion, s-CT is a valuable treatment for PLP in the early postoperative period. PMID- 1738571 TI - Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double blind, crossover trial. AB - Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails. PMID- 1738572 TI - Hyperalgesia and expanded receptive fields. PMID- 1738573 TI - Patterns of normal personality structure among chronic pain patients. AB - Fifty-nine chronic pain patients satisfying one of four previously identified pain group classifications were evaluated using the NEO Personality Inventory (NEO-PI), a standardized measure of normal adult personality structure. Minnesota Multiphasic Personality Inventory (MMPI) pain subgroups differed with respect to level of NEO-PI Neuroticism. In particular, emotionally overwhelmed pain patients as defined by multiple MMPI scale elevations had higher NEO-PI Neuroticism scores. Post hoc analyses revealed higher levels of depression, anxiety, vulnerability, and hostility in emotionally overwhelmed subjects. None of the remaining groups differed from each other on NEO-PI Neuroticism. Additionally, none of the other NEO-PI domains discriminated pain subgroups. NEO-PI profiles for pain patients (except for Neuroticism in emotionally overwhelmed patients) yielded t scores in the average range, suggesting that chronic pain patients present with a relatively normal underlying personality structure. PMID- 1738574 TI - Assessment of acute pediatric pain: do child self-report, parent ratings, and nurse ratings measure the same phenomenon? AB - The purpose of this study was to determine the factors that are associated with child, parent, and nurse ratings of acute pediatric pain and distress during venipuncture. The behavior of eighty-five pediatric cancer patients during venipuncture was recorded by trained raters, and their observations were compared with ratings of pain and distress obtained from parents, pediatric patients, and pediatric nurses. Regression analyses indicated that ratings made by the child, parent, and nurse reflect different perspectives. Nurses' ratings were based upon overt distress, parents' ratings reflected their subjective perception of the child's pain, and the child's self-report was associated with the child's chronologic age. PMID- 1738575 TI - Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brain-stem neurones. AB - Stimulation of small-diameter afferents supplying deep tissues has been shown to increase the excitability of spinal cord neurones responding to cutaneous afferent inputs. This facilitation has been implicated as integral central mechanisms of deep pain that may contribute to the tenderness and spread and/or referral of pain following injury of deep tissues. In view of the recent documentation of deep craniofacial afferent inputs, as well as cutaneous afferent inputs to the trigeminal (V) spinal tract nucleus, we wished to determine the effects of deep inputs excited by the small-fibre irritant mustard oil on trigeminal nociceptive neurones. The extracellular activity of single brain-stem neurones was recorded in subnuclei caudalis and oralis of the V spinal tract nucleus of anaesthetized rats. The neurones were classified as low-threshold mechanosensitive (LTM), wide dynamic range (WDR) and nociceptive specific (NS) on the basis of their cutaneous mechanoreceptive field properties and their responses evoked by electrical stimulation of their cutaneous afferent inputs. Injection of 5% mustard oil (2-5 microliters) into the deep masseter muscle produced a facilitatory effect in 12 of 27 nociceptive neurones tested in caudalis and in 5 of 12 nociceptive neurones in oralis. This effect was reflected in an expansion of the cutaneous mechanoreceptive field, an increase in spontaneous activity or an increase in responsivity to electrical stimulation of cutaneous afferent inputs to the neurones. The facilitation was reversible and typically became apparent within 3-5 min of the injection, reached its peak at 5 10 min, and lasted for 20-30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738576 TI - Benzodiazepines and pain: effects of midazolam on the activities of nociceptive non-specific dorsal horn neurons in the rat spinal cord. AB - The high density of GABA-benzodiazepine receptors in the superficial dorsal horn suggests a possible involvement of benzodiazepines (BZs) in the modulation of spinal pain processes. In this electrophysiological study we have examined the effects of midazolam (MZ), a water-soluble short-acting BZ, on the activities of 57 nociceptive non-specific dorsal horn cells, one in each animal. Recordings were performed at lumbar level in unanesthetized decerebrate spinal rats before and following intravenous injection of MZ (1, 2 or 5 mg/kg). The spontaneous activity was weakly and significantly but not dose dependently reduced by MZ. For the total neuronal population MZ induced no significant effect on C-fiber evoked responses, whatever the dose used. More precise analysis shows that for 45/55 neurons the responses were slightly depressed, but this effect was not dose dependent. In contrast, A delta-fiber evoked responses were markedly and dose dependently depressed. These effects of MZ were reversed by intravenous administration of the antagonist flumazenil (FZ). Despite the fact that MZ displays a very weak effect on responses due to C-fiber stimulation, the possible involvement of BZs in the modulation of nociceptive transmission at the level of the dorsal horn is discussed on the basis of clinical and experimental findings, taking into account the role of GABAergic mechanisms in sensory events. PMID- 1738577 TI - A limited arthritic model for chronic pain studies in the rat. AB - Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemic changes provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made. In this model, however, the process evolved to produce widespread polyarthritis if followed for the 6-plus-weeks necessary for chronic studies. Therefore, although it offers the researcher a reliable limited model of inflammation and nociception at the outset, for longer studies it may have all the disadvantages of the polyarthritic rat. The purpose of the present study was to produce a limited arthritic process in rats, stable over 6 weeks and suitable for behavioural and neurochemical studies of various chronic pain treatment methods. Injection (0.05 ml) of complete adjuvant containing 300 micrograms Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis, stable clinically and behaviourly from weeks 2 through 6 post injection. As revealed by clinical observations and X-ray examinations, the arthritis produced was limited anatomically, pronounced, prolonged and stable. A marked increase in sensitivity to paw pressure was seen in the affected limb. Animals gained weight and remained active, indicating little systemic disturbance as opposed to polyarthritic rats. We propose this limited model of arthritis as a suitable alternative to the polyarthritic rat for prolonged studies. PMID- 1738578 TI - Met-enkephalin and beta-endorphin are not involved in the analgesic action of transcutaneous vibratory stimulation. AB - Although the analgesic effects observed during the application of vibration may be attributable to neuronal inhibition of the pain pathways, this does not account for the fact that pain relief sometimes persists for a long time after the end of vibration treatment. Two experiments were carried out in order to determine whether pain relief might involve the release of endogenous opioids. In the first experiment, we studied the effects of injecting either a morphine antagonist, naloxone (0.4 mg), or a placebo, on the analgesia resulting from vibratory stimulation in 12 patients suffering from acute or chronic pain. In the second experiment, the Met-enkephalin and beta-endorphin levels were determined before and after 30 min vibratory stimulation in the cerebrospinal fluid of 8 patients suffering from chronic pain and 1 control subject, all of whom had been fitted with a ventriculo-peritoneal drain which made it possible to collect samples of cerebrospinal fluid painlessly. The results of these experiments show, on the one hand, that the effects of naloxone on the vibration-induced analgesia did not differ from those of the placebo and, on the other hand, that no increase in the Met-enkephalin or beta-endorphin levels occurred concomitantly with pain relief. It will therefore be necessary to investigate other mechanisms as possible means of explaining the post-vibratory analgesic effects. PMID- 1738579 TI - The representation of prolonged and intense, noxious somatic and visceral stimuli in the ventrolateral orbital cortex of the cat. AB - The responses of single neurones in the ventrolateral orbital (VLO) cortex to noxious pinch, heating of the skin, twisting of the joints and distension of the gall bladder were studied in cats anaesthetized with halothane. Of 60 neurones studied, 44 responded to prolonged (greater than 10 sec) stimuli that were well within the noxious range. Neurones were relatively unresponsive to innocuous stimuli or to the transient application of noxious stimuli. Many single neurones responded to a variety of modalities of noxious stimuli (e.g., skin heating and gall bladder distension). Many neurones studied showed a fluctuating level (5-15 Hz) of ongoing spontaneous activity. Neurones responded with either an increased frequency of spikes (excitation) or an inhibition of spontaneous discharge, irrespective of the source of noxious stimulation. Noxious stimuli delivered simultaneously to two different tissues (e.g., skin and visceral) sometimes produced excitation of the neurone under study, to levels above that produced by the application a noxious stimulus to only one of the tissues. Receptive fields were often large involving both contralateral and ipsilateral areas of the body, as well as both fore and hind limbs. No evidence of somatotopic organization was obtained. The responses of some neurones outlasted the application of the stimuli by many minutes. It is concluded that single neurones in the ventrolateral orbital cortex respond to the prolonged application of intensely noxious stimuli to a variety of body tissues, in a manner that is in keeping with the involvement of this cortical area in both the physiological, autonomic and experiential components of the affective-motivational aspect of pain. Furthermore, from the consequences of lesion studies in man and animals, it is proposed that the activation of cells in the orbital cortex by a variety of noxious stimuli reflects its more general role in the development and maintenance of behaviour in response to negative reinforcement of both social and physical origins. PMID- 1738580 TI - Trends in physiologic and pharmacologic interventions in pediatric nuclear medicine. PMID- 1738581 TI - Pediatric body CT. PMID- 1738582 TI - Magnetic resonance imaging in the pediatric patient. AB - Magnetic resonance imaging is an excellent technique for evaluation of pediatric pathology. When combined with other imaging modalities, MRI represents a powerful addition to the radiologist's diagnostic armamentarium. Magnetic resonance imaging has demonstrated great potential for noninvasively characterizing physical and chemical properties of various tissues and in some cases has provided information not available by any other technique. Future developments may result in much faster scan times, better biochemical characterization (magnetic resonance spectroscopy), and improved images. Certainly, the full potential of this extraordinary imaging technique has not been reached. As prospective studies of MRI evolve, this technique will play an increasing role in assessing pediatric disease. PMID- 1738583 TI - Pediatric diagnostic imaging: to see or not to see. PMID- 1738584 TI - Perspectives on pediatric imaging: 1992. PMID- 1738585 TI - Pediatric ultrasound in the 1990s. PMID- 1738586 TI - Diagnostic sonography of the fetus: a guide to the evaluation of the neonate. PMID- 1738587 TI - Inhibition of DNA synthesis at the hemimethylated pBR322 origin of replication by a cell membrane fraction. AB - The replication of both ColE1-type plasmids and plasmids bearing the origin of replication of the Escherichia coli chromosome (oriC) has been shown to be inhibited by hemimethylation of adenine residues within GATC sequences. In the case of oriC plasmids, this inhibition was previously shown to be mediated by the specific affinity of the hemimethylated origin DNA for an outer cell membrane fraction. Here, we suggest that a similar mechanism is operating in the case of the ColE1-like plasmid pBR322 as (i) a hemimethylated DNA fragment carrying the promoter for the RNA which primes DNA synthesis (RNAII) is specifically bound by the same membrane fraction and, (ii) the addition of the membrane fraction to a soluble assay of pBR322 replication results in preferential inhibition of initiation on the hemimethylated template. We suggest that membrane sequestration of hemimethylated origin DNA and/or associated replication genes following replication may be a common element restricting DNA replication to precise moments in the cell cycle. PMID- 1738588 TI - A CT promoter element binding protein: definition of a double-strand and a novel single-strand DNA binding motif. AB - Numerous genes contain promoter elements that are nuclease hypersensitive. These elements frequently possess polypurine/polypyrimidine stretches and are usually associated with altered chromatin structure. We have previously isolated a clone that binds a class of CT-rich promoter elements. We have further characterized this clone, termed the nuclease-sensitive element protein-1, or NSEP-1. NSEP-1 binds both duplex CT elements and the CT-rich strand of these elements in a 'generic' sequence specific manner and has overlapping but distinct single-and double-strand DNA binding domains. The minimal peptide region sufficient for both duplex and single-strand DNA binding includes two regions rich in basic amino acids flanking an RNP-CS-1 like octapeptide motif. Deletion analysis shows that the single-strand DNA binding activity is mediated by the RNP-CS-1 like octapeptide motif and is the key peptide region necessary for single-strand binding. NSEP-1's affinity for CT rich promoter elements with strand asymmetry in addition to its double- and single-strand DNA binding properties suggests that it may be a member of a class of DNA binding proteins that modulate gene expression by their ability to recognize DNA with unusual secondary structure. PMID- 1738589 TI - Human calcitonin gene regulation by helix-loop-helix recognition sequences. AB - Human calcitonin (CT) gene transcription is regulated by proximal 5' flanking sequences which mediate cAMP-induced expression, and by a distal basal enhancer region. Using transient expression of CT-CAT constructs, we showed that the basal enhancer is active in a CT-producing small cell lung cancer cell line (DMS53) and the thyroid C cell derived tumor line, TT, but is inactive in non-CT-producing cell lines. In deletional and direct mutational analyses of the distal enhancer region, disruption of two elements resembling recognition sequences for the helix loop-helix (HLH) family of transcriptional regulatory proteins resulted in a significant loss of basal transcriptional enhancer action. These results suggest that HLH recognition motifs may mediate a significant portion of constitutive CT gene transcriptional activity in these cells. Nuclear protein extracts from DMS53 cells formed specific binding complexes with oligonucleotides containing two of these candidate enhancer sequences. However, proteins capable of binding to these CT gene HLH consensus recognition sites were not restricted to CT-producing cells. We conclude that members of the HLH protein family, some expressed ubiquitously and some expressed or activated in a tissue-restricted fashion, may combine to enhance CT gene transcription in tumor cells of neuroendocrine derivation. PMID- 1738590 TI - EGF-induced jun B-expression in transfected P19 embryonal carcinoma cells expressing EGF-receptors is dependent on Jun D. AB - The TPA-inducible transcription factor AP-1, consisting of homo- or hetero-dimers of members of the Jun- and Fos-families, regulates transcription of a wide variety of genes containing the TPA response element (TRE). In P19 embryonal carcinoma (EC) cells, Jun D is the only component of AP-1 expressed, while in these cells until now none of the members of the jun- and fos-families have been found to be inducable by external stimuli. Here we demonstrate that Jun B is the only member of the Jun- and Fos-families that is induced by Epidermal Growth Factor (EGF) in transfected murine P19 EC cells, expressing functional human EGF receptors (hEGF-Rs). Induction of jun B can be mimicked in wild type P19 EC cells by the synergistic action of the phorbol ester TPA and the calcium ionophore A23187, through activation of signal transduction pathways, that are activated simultaneously by EGF. The EGF induced jun B expression in the hEGF-R expressing P19 EC cells is mediated by an inverted repeat (IR) sequence in the jun B promoter, previously shown to be responsive to both PKC and PKA signal transduction. Transactivation of the IR sequence by EGF can be blocked completely by prior expression of antisense Jun D, but not by antisense c-Jun. These studies therefore implicate Jun D in the regulation of immediate early gene expression by external stimuli. PMID- 1738591 TI - A simple method for global sequence comparison. AB - A simple method of sequence comparison, based on a correlation analysis of oligonucleotide frequency distributions, is here shown to be a reliable test of overall sequence similarity. The method does not involve sequence alignment procedures and permits the rapid screening of large amounts of sequence data. It identifies those sequences which deserve more careful analysis of sequence similarity at the level of resolution of the single nucleotide. It uses observed quantities only and does not involve the adoption of any theoretical model. PMID- 1738592 TI - Sequence and base modifications of two phenylalanine-tRNAs from Thermus thermophilus HB8. PMID- 1738593 TI - Differential detection of multiple DNA-binding complexes using dissimilar polyanion competitors. PMID- 1738594 TI - Characterization of (CA)n microsatellites with degenerate sequencing primers. PMID- 1738595 TI - Non-fusion proteins expressed in E. coli: detection by alpha-complementation (blue/white selection). PMID- 1738596 TI - PCR using a thermostable polymerase with 3' to 5' exonuclease activity generates blunt products suitable for direct cloning. PMID- 1738597 TI - Nonisotopic SSCP and competitive PCR for DNA quantification: p53 in breast cancer cells. PMID- 1738598 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1738599 TI - Structural features in TAR RNA of human and simian immunodeficiency viruses: a phylogenetic analysis. AB - A comparative analysis of TAR RNA structures in human and simian immunodeficiency viruses reveals the conservation of certain structural features despite the divergence in sequence. Both the TAR elements of HIV-1 and SIV-chimpanzee can be folded into relatively simple one-stem hairpin structures. Chemical and RNAase probes were used to analyze the more complex structure of HIV-2 TAR RNA, which folds into a branched hairpin structure. A surprisingly similar RNA conformation can be proposed for SIV-mandrill, despite considerable divergence in nucleotide sequence. A third structural presentation of TAR sequences is seen for SIV african green monkey. These results are generally consistent with the classification of HIV-SIV viruses in four subgroups based on sequence analyses (both nucleotide- and amino acid-sequences). However, some conserved TAR structures were detected for members of different virus subgroups. It is therefore proposed that RNA structure analysis might provide an additional tool for determining phylogenetic relationships among the HIV-SIV viruses. PMID- 1738601 TI - Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation. AB - Iron regulatory factor (IRF), also called iron responsive element-binding protein (IRE-BP), is a cytoplasmic RNA-binding protein which regulates post transcriptionally transferrin receptor mRNA stability and ferritin mRNA translation. By using the polymerase chain reaction (PCR) and the sequence published by Rouault et al. (1990) a probe was derived which permitted the isolation of three human IRF cDNA clones. Hybridization to genomic DNA and mRNA, as well as sequencing data indicated a single copy gene of about 40 kb specifying a 4.0 kb mRNA that translates into a protein of 98,400 dalton. By in vitro transcription of a assembled IRF cDNA coupled to in vitro translation in a wheat germ extract, we obtained full sized IRF that bound specifically to a human ferritin IRE. In vitro translated IRF retained sensitivity to sulfhydryl oxidation by diamide and could be reactivated by beta-mercaptoethanol in the same way as native placental IRF. An IRF deletion mutant shortened by 132 amino acids at the COOH-terminus was no longer able to bind to an IRE, indicating that this region of the protein plays a role in RNA recognition. Placental IRF has previously been shown to migrate as a doublet on SDS-polyacrylamide gels. After V8 protease digestion the heterogeneity was located in a 65/70 kDa NH2-terminal doublet. The liberated 31 kDa COOH-terminal polypeptide was found to be homogeneous by amino acid sequencing supporting the conclusion of a single IRF gene. PMID- 1738602 TI - In vitro cleavage of double- and single-stranded DNA by plasmid RSF1010-encoded mobilization proteins. AB - We have used purified RSF1010 mobilization proteins to reproduce in vitro a strand-specific nicking at the plasmid origin of transfer, oriT. In the presence of Mg2+, the proteins MobA (78-kDa form of RSF1010 DNA primase), MobB, and MobC and supercoiled or linear duplex oriT DNA form large amounts of a cleavage complex, which is characterized by its sensitivity to protein-denaturant treatment. Upon addition of SDS to such a complex, a single strand break is generated in the DNA, and MobA is found linked to the 5' nick terminus, presumably covalently. The double-strand nicking activity of MobA requires, in addition to Mg2+, the presence of MobC and is stimulated by the presence of MobB. The nick site has been shown by DNA sequencing to lie at the position cleaved in vivo during transfer, between nucleotides 3138/3139 in the r strand of RSF1010. We have found that MobA will also cleave DNA at sites other than oriT if the DNA is present in single-stranded form. Breakage in this case occurs in the absence of denaturing conditions, and after prolonged incubation, reclosure can be demonstrated. PMID- 1738603 TI - Retinoblastoma susceptibility genes contain 5' sequences with a high propensity to form guanine-tetrad structures. AB - Retinoblastoma susceptibility genes contain significant runs of oligoguanine at their 5' ends. Oligonucleotides having these sequences underwent complex formation in the presence of sodium ions, in which there was association of four strands. Formation of this structure was completely prevented if guanine was replaced by 7-deazaguanine, indicating the importance of guanine N7 in the formation of the complex. Complex formation lead to protection of guanine N7 against methylation by dimethyl sulphate, but thymine bases located between oligoguanine blocks were reactive to osmium tetroxide. There was also some sensitivity to S1 nuclease to the 5' side of the oligoguanine block. The results show that the G-rich regions of the mouse and human retinoblastoma susceptibility genes have a propensity to undergo tetraplex formation of the kind demonstrated in the immunoglobulin switch region. PMID- 1738604 TI - 7-Deazapurine containing DNA: efficiency of c7GdTP, c7AdTP and c7IdTP incorporation during PCR-amplification and protection from endodeoxyribonuclease hydrolysis. AB - The enzymatic synthesis of 7-deazapurine nucleoside containing DNA (501 bp) is performed by PCR-amplification (Taq polymerase) using a pUC18 plasmid DNA as template and the triphosphates of 7-deaza-2'-deoxyguanosine (c7Gd), -adenosine (c7Ad) and -inosine (c7Id). c7GdTP can fully replace dGTP resulting in a completely modified DNA-fragment of defined size and sequence. The other two 7 deazapurine triphosphates (c7AdTP) and (c7IdTP) require the presence of the parent purine 2'-deoxyribonucleotides. In purine/7-deazapurine nucleotide mixtures Taq polymerase prefers purine over 7-deazapurine nucleotides but accepts c7GdTP much better than c7AdTP or c7IdTP. As incorporation of 7-deazapurine nucleotides represents a modification of the major groove of DNA it can be used to probe DNA/protein interaction. Regioselective phosphodiester hydrolysis of the modified DNA-fragments was studied with 28 endodeoxyribonucleases. c7Gd is able to protect the DNA from the phosphodiester hydrolysis in more than 20 cases, only a few enzymes (Mae III, Rsa I, Hind III, Pvu II or Taq I) do still hydrolyze the modified DNA. c7Ad protects DNA less efficiently, as this DNA could only be modified in part. The absence of N-7 as potential binding position or a geometric distortion of the recognition duplex caused by the 7-deazapurine base can account for protection of hydrolysis. PMID- 1738600 TI - Compilation of vertebrate-encoded transcription factors. PMID- 1738605 TI - The expression of the amyloid precursor protein (APP) is regulated by two GC elements in the promoter. AB - The structure of the promoter of the human APP gene resembles that of housekeeping genes, with the presence of a GC-rich region and the lack of a canonical TATA box. Since analysis of the expression of the APP gene, especially at the transcriptional level, might reveal factors or elements, which influence amyloid formation in Alzheimer's disease, a 5' deletion analysis of the APP promoter was performed, leading to the identification of an activating DNA fragment (Ac), acting also on a heterologous promoter. DNaseI-footprint analysis revealed three protected regions on the Ac fragment. Further gene transfer experiments showed, that at least two elements, designated A and C, confer transcriptional activity in HeLa cells. Whereas the proximal element A is a 19bp long GC-rich DNA sequence, the distal element C is a GC-palindrome with the sequence 5'GCGGCGCCGC. PMID- 1738606 TI - Identification of the template binding polypeptide in the pea chloroplast transcriptional complex. AB - We have identified the template-binding polypeptide in the pea chloroplast transcriptional complex by photoaffinity labelling. This polypeptide has an apparent molecular weight of about 150 kDa and binds to both, chloroplast ribosomal (16S rRNA) and messenger (psbA) promoters. The 16S rRNA and psbA promoters were amplified from chloroplast DNA by the polymerase chain reaction and labelled with a photoactive analogue of TTP, 5-bromodeoxy UTP, as well as with alpha-32P-dCTP. Using the filter-binding assay, the conditions for binding of the RNA polymerase complex to chloroplast promoters were optimized. The polypeptide directly interacting with the template was photo-crosslinked to it and resolved by denaturing gel electrophoresis. The photoaffinity labelling of the 150 kDa polypeptide was dependent on photoactivation by UV irradiation, and the presence of chloroplast promoters. Competition experiments showed that the protein formed a strong interaction with the plastid promoters which could not be displaced by lambda-phage DNA or synthetic polynucleotides. The photo-crosslinked and nuclease-treated promoter-polypeptide complex was resistant to further digestion with DNase and RNase, but could be hydrolyzed by Proteinase K. Binding of the promoters by the 150 kDa polypeptide could not be surpressed by transcription inhibitors like rifampicin and alpha-amanitin. However, heparin (0.001%) inhibited the formation of the enzyme-promoter complex, and interfered with the photoaffinity labelling of the 150 kDa polypeptide. The extent of photoaffinity labelling of 150 kDa polypeptide exhibits some degree of correlation to total transcriptional activity under various salt concentrations. The results demonstrate that the 150 kDa polypeptide is a functional template binding polypeptide of the pea chloroplast transcription complex. PMID- 1738607 TI - Processing of chimeric introns in dicot plants: evidence for a close cooperation between 5' and 3' splice sites. AB - Splice sites of vertebrate introns are generally not recognized in plant cells. Several lines of evidences have led to the proposal that the mechanism of 3' splice site selection differs in plants and animals (K. Wiebauer, J.J. Herrero, and W. Filipowicz, Mol. Cell. Biol. 8:2042-2051, 1988). To gain a better insight into the mechanistic differences between plant and animal splicing, we constructed chimeric introns consisting partly of dicotyledonous plant and partly of animal intron sequences. Splicing of these chimeric introns was analyzed in transiently transfected tobacco protoplasts. The results show that there are no principal sequence or structural differences between the 3' splice regions of plants and animals. Furthermore, evidence is provided that cooperation between 5' and 3' splice sites takes place and influences their mutual selection. PMID- 1738609 TI - Chlamydomonas reinhardtii telomere repeats form unstable structures involving guanine-guanine base pairs. AB - Unusual DNA structures involving four guanines in a planar formation (guanine tetrads) are formed by guanine-rich (G-rich) telomere DNA and other G-rich sequences (reviewed in (1)) and may be important in the structure and function of telomeres. These structures result from intrastrand and/or interstrand Hoogsteen base pairs between the guanines. We used the telomeric repeat of Chlamydomonas reinhardtii, TTTTAGGG, which contains 3 guanines and has a long interguanine A + T tract, to determine whether these sequences can form intrastrand and interstrand guanine tetrads. We have found that ss (TTTTAGGG)4 can form intrastrand guanine tetrads that are less stable than those formed by more G-rich telomere sequences. They are not only more stable, but also more compact, they are more stable in the presence of K+ than they are in the presence of Na+. While ds oligonucleotides with ss 3' overhangs of (TTTTAGGG)2 can be observed to associate as dimers, formation of this interstrand guanine tetrad structure occurs to a very limited extent and requires very high G-strand concentration, high ionic strength, and at least 49 hours of incubation. Our results suggest that, if telomere dimerization occurs in vivo, it would require factors in addition to the TTTTAGGG telomere sequence. PMID- 1738608 TI - Sensitive detection of RNAs in single cells by flow cytometry. AB - A rapid and sensitive fluorescent in situ hybridization method has been developed to probe RNA contents of individual cells by flow cytometry. Fixed cells in suspension were hybridized with 5' end-fluorophore-labeled oligodeoxynucleotides complementary to defined regions of the RNA of interest and analyzed by flow cytometry. With this method, we monitored combinations of histone H4 mRNA, 18S rRNA and 28S rRNA levels in synchronized HeLa S3 cells by multicolor analysis. A fluorescence signal equivalent to 1800 copies of histone H4 mRNA per cell was detected with signal-to-background ratio of 5.4. If non-specific binding of the fluorophore-labeled probe can be reduced, as few as 100 copies of mRNA of the size of H4 could be detected in individual cells by flow cytometry. PMID- 1738610 TI - Caring in its "proper place": race and benevolence in Charleston, SC, 1813-1930. PMID- 1738611 TI - "Half a loaf is better than no bread": public health nurses and physicians in Ontario, 1920-1925. PMID- 1738612 TI - An historical perspective of Confederate nursing during the Civil War, 1861-1865. PMID- 1738613 TI - Nurses under attack: the Lewes Riot and the Society of St. Margaret. PMID- 1738614 TI - The nature of history: meditations on Clio's craft. PMID- 1738615 TI - The changing face of nursing. PMID- 1738616 TI - Aspirations unattained: the story of the Illinois Training School's search for university status. PMID- 1738617 TI - The spirituality of Florence Nightingale. PMID- 1738618 TI - Watchful vigilance: nursing care, technology, and the development of intensive care units. PMID- 1738619 TI - Research and reform: community nursing and the Framingham Tuberculosis Project, 1914-1923. PMID- 1738620 TI - A worry lifted. PMID- 1738621 TI - Stillbirth rites. PMID- 1738622 TI - Media watch. PMID- 1738624 TI - The value of nursing. Telling stories, telling moments. PMID- 1738623 TI - Two cheers for matron. PMID- 1738625 TI - Finding the right words. PMID- 1738626 TI - One from the heart. PMID- 1738627 TI - The value of nursing. Prove your worth. PMID- 1738628 TI - Encouraging research. PMID- 1738630 TI - The stigma of infertility. PMID- 1738629 TI - Making sense of surgical flaps. PMID- 1738631 TI - Grading practice. PMID- 1738632 TI - A very personal problem. PMID- 1738633 TI - General practice viewed from A&E. PMID- 1738634 TI - Visiting hours in intensive care units. PMID- 1738635 TI - Dressing ability after stroke. PMID- 1738636 TI - Primary nursing. Network for change. PMID- 1738637 TI - Primary nursing. Whose plan is it anyway? PMID- 1738638 TI - Allowing for loss. PMID- 1738639 TI - Birth of ill health. PMID- 1738640 TI - Pass the hat. PMID- 1738641 TI - No place to go. PMID- 1738642 TI - Road safety. PMID- 1738643 TI - Proceeding with caution. PMID- 1738644 TI - Foundation for success. PMID- 1738645 TI - Drugs update. Stopping the drugs trolley. PMID- 1738647 TI - Record recovery. PMID- 1738646 TI - Simon's nursing assessment. PMID- 1738648 TI - Hungarian research. PMID- 1738649 TI - Visiting time. PMID- 1738650 TI - Putting parents in the picture. PMID- 1738651 TI - Action replay? PMID- 1738652 TI - The value of nursing. Sound judgments. PMID- 1738653 TI - Systems of life. Bone and bones. 2. PMID- 1738654 TI - Changes in the year before death 1969-87. PMID- 1738655 TI - A support group for care providers. PMID- 1738656 TI - Diagnosing change in job structures. PMID- 1738657 TI - Practising research-based teaching. PMID- 1738658 TI - How to use questioning in the classroom. PMID- 1738659 TI - Nutrition, Dehydration before death. PMID- 1738661 TI - Open learning programme. P5: client assessment. Part (i): Assessment in context [continuing education credit]. PMID- 1738660 TI - Parenteral nutrition. PMID- 1738662 TI - Prejudiced treatment. Interview by Peter Mason. PMID- 1738663 TI - Homeless and healthless. PMID- 1738664 TI - Bedding down. PMID- 1738666 TI - Looking after junior. PMID- 1738665 TI - An end to glue ear? PMID- 1738667 TI - What price tranquillity? PMID- 1738668 TI - Death with dignity. Christianity. PMID- 1738669 TI - Infection control. Protecting the patient at risk. PMID- 1738670 TI - Open learning. Building a career. PMID- 1738671 TI - Safe as houses. PMID- 1738672 TI - The value of nursing. Professional demands. PMID- 1738673 TI - Evaluating syringe drivers. PMID- 1738674 TI - Training in the twenties. PMID- 1738675 TI - Compression healing of venous ulcers. PMID- 1738676 TI - Parents' responses to a child's hospitalisations. PMID- 1738677 TI - Does nose blowing help hearing in glue ear? PMID- 1738678 TI - Canadian competence. PMID- 1738679 TI - Elderly people in A&E. PMID- 1738680 TI - Computing in practice: information management & technology. Informed choice. PMID- 1738681 TI - Professional development module. P6: facilitating learning. Part (I): Learning and communication. PMID- 1738682 TI - Suggested shift changes threaten ability to provide patient care. PMID- 1738683 TI - Room service. PMID- 1738684 TI - Stoma care? PMID- 1738685 TI - Lost rights. PMID- 1738686 TI - Places for dying? PMID- 1738687 TI - Up to standard. PMID- 1738688 TI - Balancing acts. PMID- 1738689 TI - Body politic. Class struggle. PMID- 1738690 TI - Families and HIV. Rebels at risk. PMID- 1738691 TI - Families and HIV. United we stand. PMID- 1738692 TI - Health and social services. PMID- 1738693 TI - Companions in casualty. PMID- 1738694 TI - Mental health--blyth spirits. PMID- 1738695 TI - Death with dignity--Jehovah's Witnesses. PMID- 1738696 TI - Positive progress--care study. PMID- 1738697 TI - Where did you get that cap? PMID- 1738698 TI - Drinking safely. PMID- 1738699 TI - The role of the nurse on the consultant's ward round. PMID- 1738700 TI - Too many tests? PMID- 1738701 TI - Continence--breaking point. PMID- 1738702 TI - Continence--feeling off-colour. PMID- 1738703 TI - Anterior dislocations of the hip. Femoral head indentation fracture. PMID- 1738704 TI - Radiologic case study. Giant synovial cysts. PMID- 1738705 TI - Wu's bunionectomy. PMID- 1738707 TI - Gross polyethylene failure in total knee arthroplasty. AB - A total of 12 total knee replacements in nine patients with evidence of gross polyethylene failure at the time of revision surgery were identified. There were nine tibial and three patellar component failures. The average time from index to revision arthroplasty was 6 years (range: 0.75 to 9.63). A retrospective cohort group was identified based on date of operation. The average patient weight of the initial group was 89.6 kg (range: 76 to 104 kg), compared with 74.8 kg (range: 47 to 108 kg) (P = .045) in the control group. There was a male sex preponderance in the failure group (P = .045). The average height of the study group was 176 cm, compared to 161 cm for the control group (P = .003). Using the modified OASDI scale, the failure group had a higher activity level (P = .023). Pre-revision limb alignment in patients with failed TKA was statistically different from controls and served as an indication of polyethylene failure (P = .04). The selection of modular prosthetic component systems that allow for easy polyethylene revision is indicated in the high risk patient group identified. Close follow up is needed to minimize the sequela of polyethylene failure. PMID- 1738706 TI - Total hip arthroplasty for protrusio acetabuli: a 3- to 9-year follow up of the Heywood technique. AB - Thirty-five total joint arthroplasties (34 patients) were performed in patients who had protrusio acetabuli. Twenty-nine percent of the patients had acetabular protrusio of grade I, while 71% had grade II and grade III protrusio. The mean follow up was 4 years (range: 3 to 9). Cemented acetabular components were used in 11 hips; 24 hips received an uncemented porous coated acetabular component. The patient evaluations included preoperative and postoperative Harris Hip Ratings and standard radiographs. In all cases, the medial wall defect was reconstructed with the solid autogenous femoral head as described by Heywood. The mean preoperative Harris Hip Rating was 45 (range: 30 to 60 points), and the postoperative mean was 85 (range: 70 to 100 points). Radiographically, the preoperative protrusio measured a mean of 8.8 mm (range: 6 to 18 mm), and the mean postoperative placement of the femoral head was 10 mm lateral to Kohler's line (range: 6 to 13 mm). There were no acetabular component failures and no acetabular bone graft resorptions. All autogenous grafts were incorporated to the host radiographically by 1 year post-surgery. This study corroborates previous work which suggests that medial-placed bone grafting is not resorbed and consolidates with the host bone. We find this technique extremely useful in dealing with this technical problem. PMID- 1738708 TI - The meniscus. AB - Abnormalities and injuries of the meniscus have been studied for decades. An expanded knowledge of knee biomechanics and the advent of arthroscopy have changed the diagnosis and treatment of meniscal pathology over the past decade. This review highlights some of the relevant literature concerning the meniscus. PMID- 1738709 TI - Three-dimensional CT reconstruction for assessment of Pipkin fracture dislocations of the hip. PMID- 1738710 TI - Intraosseous lipoma of the humerus. PMID- 1738711 TI - Vascular injury during cementless total hip arthroplasty. PMID- 1738712 TI - Analysis of the discoid meniscus in Koreans. AB - Discoid meniscus is a relatively common disorder of the knee in Koreans. Its arthroscopic treatment is one of the most technically demanding procedures of this field. The purposes of this study were to define the clinical features of the discoid meniscus in Koreans and to suggest an adequate arthroscopic technique. We performed arthroscopic meniscectomy on 37 knees with a lateral discoid meniscus. The average length of follow up was 21 months. The presence of synovial hypertrophy in the knee with discoid was significantly higher than that with a non-discoid meniscal lesion. A medial midpatellar portal for the arthroscope is advisable for clean arthroscopic surgery in this situation. We obtained satisfactory results through the partial resection of the discoid meniscus, leaving the normal semilunar-shaped meniscus intact as much as possible. PMID- 1738713 TI - The relationship between the treatment of congenital dislocation of the hip and avascular necrosis. AB - The most important complication following the treatment of congenital dislocation of the hip is avascular necrosis. The potential sequelae that may arise after the onset of avascular necrosis are worse than if the hip remained dislocated. We evaluated 38 hips in which avascular necrosis developed after reduction. The average patient age at the time of reduction was 4.3 years, with a follow up of 6 to 15 years. Twelve hips had closed reduction and 26 had open reduction. Following reduction, 8 hips had Type I, 6 had Type II, 9 had Type III, and 15 had Type IV avascular necrosis. In this article, we evaluate our cases and review current literature on the subject. Close follow up and timely interventions can reduce potential sequelae to a minimum. PMID- 1738714 TI - Chronic lateral ankle instability--inversion sprains: Part I. PMID- 1738715 TI - Human immunodeficiency virus: occupational risk for surgeons. PMID- 1738716 TI - Prophylactic cerclage: a method of preventing femur fracture in uncemented total hip arthroplasty. AB - The incidence of femur fracture in non-cemented hip arthroplasty has been reported to be between 4.1% and 27.8%. To quantitate the hoop stress generated during insertion of a femoral broach in total hip arthroplasty and determine the effect of cerclage with both braided cable and wire, we harvested 14 pairs of embalmed cadaver femurs. These were reamed and broached to duplicate the surgical technique of inserting a straight non-cemented femoral component. Group one consisted of eight matched cadaver femurs which were tested using a single 2.0 mm chrome-cobalt cable placed around the calcar of one femur, with the other serving as a control. Group two consisted of five matched cadaver femurs which were tested using a single 18 gauge cerclage wire in the same manner. In group one, the femurs serving as controls were found to have a mean microstrain of (1425.00 +/- 1180.19). The eight femurs tested with a 2 mm cable were determined to have a mean microstrain of (4179 +/- 2853.89). In group two, the femurs serving as controls were found to have a mean microstrain of (962.60 +/- 956.78). The five femurs in group two tested with a cerclage wire were determined to have a mean microstrain of (1112.00 +/- 975.66). Using a paired t-test, statistical significance was achieved with a confidence level of P less than or equal to .01 in group one. Prophylactic wiring of the proximal femur with 2 mm cable increases the hoop stress resistance and, therefore, should decrease the incidence of intraoperative femur fractures in uncemented total hip arthroplasty. PMID- 1738717 TI - The usefulness of MRI in evaluating menisci after meniscus repair. AB - We reviewed magnetic resonance imaging (MRI) scans of 15 asymptomatic patients at 6 months to 1 year following meniscal repair procedures. All of the patients were found to have persistent MRI signals in the region of the repair. Nine of the 17 meniscal repairs in the 15 patients had persistent grade 3 signals. Arthrograms were performed on six patients (eight meniscal repairs). Seven of these postoperative menisci showed grade 3 signals on MRI. Only one meniscus was shown to have a complete tear by arthrogram. There were no false negative scans. The overall accuracy, defined as the percentage of postoperative menisci correctly diagnosed by MRI, was 38% (3/8). MRI is a useful preoperative diagnostic study following knee injury. This report demonstrates, however, that present MRI modalities are unable to distinguish between scar tissue of healed meniscal repairs and meniscal tears. Therefore, it is not a useful diagnostic tool in evaluating reinjury following successful meniscal repair. PMID- 1738718 TI - Operative treatment of bicondylar intraarticular fractures of the distal humerus. AB - Orthopedists' lack of consensus on treatment regimens for bicondylar fractures of the distal humerus warrants further review of this uncommon fracture. We present a series of 17 bicondylar fractures of the distal humerus that had a minimum follow up of 2 years. Of these fractures, the 13 that were treated exclusively with internal fixation had 92% excellent or good results. The operative technique we describe is modified from the technique recommended by the AO group. We have found it helpful to use the radial column as the site of primary fixation with a 3.5 mm dynamic compression plate in the sagittal plane. Additional fixation is provided by a reconstruction plate placed posteriorly on the ulnar column in the coronal plane. This system of dual plates in perpendicular planes provides rigidity for early motion which, when supervised, is beneficial to a satisfactory outcome. PMID- 1738719 TI - A comparison of epidural and non-epidural anesthesia and analgesia in total hip or knee arthroplasty patients. AB - This retrospective study explores a number of variables encountered with the use of either epidural or non-epidural anesthesia and analgesia. Postoperative mobility, amount of narcotic used, incidence of blood transfusion, length of stay, and presence of urinary retention, pruritus, nausea and vomiting, or respiratory depression were compared in a group of 101 consecutive patients scheduled for total hip or knee arthroplasty. Fifty-two patients received epidural anesthesia and analgesia; the remaining 49 received non-epidural anesthesia, followed by standard IM/IV postoperative analgesia. Epidural patients required significantly less narcotic than the non-epidural group. There were significantly fewer blood transfusions in the epidural group; however, epidural patients had significantly increased incidence of urinary retention and pruritus. The use of epidural anesthesia and analgesia for total hip and knee arthroplasty patients has definite merit, but is most safely administered in a monitored, skilled nursing unit. PMID- 1738720 TI - Evaluation of the cervical spine in the emergency setting: who does not need an X ray? PMID- 1738721 TI - Polymethylmethacrylate-antiblastic drug compounds: an in vitro study assessing the cytotoxic effect in cancer cell lines--a new method for local chemotherapy of bone metastasis. AB - An in vitro study was performed assessing the pharmacologic properties of polymethylmethacrylate (PMMA)-antiblastic agent (doxorubicin and cisplatinum) mixtures in normal and neoplastic cell lines cultures. The study's aim was to analyze the polymerization capacity of PMMA in the presence of doxorubicin and cisplatinum, the release of drug from the mixture, the kinetics of release, and the effect of the released drugs in normal and neoplastic cell cultures. Our data show that even at high concentrations neither doxorubicin nor cisplatinum inhibit the polymerization of PMMA. Moreover, mixtures in vitro can release the antiblastic drug which maintains its pharmacologic activity on sensitive neoplastic cells. Therefore, the PMMA-antiblastic drug mixtures, along with current anti-cancer therapy (systemic chemotherapy and radiation therapy), may provide better local control of the metastatic lesion and of some bone tumors. PMID- 1738722 TI - Isolated bilateral tarsal navicular fracture-dislocation. PMID- 1738723 TI - Complex dorsal dislocation of the interphalangeal joint of the great toe. PMID- 1738724 TI - Triceps avulsion fracture in a weightlifter. PMID- 1738725 TI - Fusobacterium nucleatum pyomyositis. PMID- 1738726 TI - Fixation screws of the acetabular component in hip replacement. PMID- 1738727 TI - Arthroscopic capsular suture for anterior instability of the shoulder. AB - We assessed the results of arthroscopic transglenoid capsular suture in eight recurrent traumatic unidirectional anterior dislocations. At an average follow up of 11 months, ranging from eight to 18 months, assessment by Rowe's scoring system were excellent or good in all shoulders. There were no redislocations and all patients achieved near full, painless range of motion. There were no complications. We propose a new classification of anterior capsular lesions (Bankart lesion) and we describe the details of the arthroscopic suture technique. We conclude that arthroscopic suture is an effective method with low surgical morbidity and low cost in the treatment of recurrent anterior dislocation of the shoulder. PMID- 1738728 TI - Salvage of infected total hip replacement: use of antibiotic/PMMA spacer. PMID- 1738729 TI - Total ankle joint replacement: a clinical follow up. AB - The TPR total ankle joint replacement system (Smith & Nephew Richards) was implanted in 30 ankles in 25 patients. Twenty-three ankles in 18 patients were followed; 21 had rheumatoid arthritis and two had osteoarthritis. The average age at surgery was 62 years (range: 37 to 77), and the average follow up was 59 months (range: 37 to 89). The improvement was especially obvious with respect to pain and function. The average walking distance improved from 260 m preoperatively to 975 m postoperatively. Even though there was some improvement with respect to pain and function, the results of the study are disappointing in comparison to studies of ankle arthrodesis. PMID- 1738730 TI - Chronic lateral ankle instability--inversion sprains: Part II. PMID- 1738731 TI - Radiologic case study. MRI and sports injuries. PMID- 1738732 TI - Giant cell arteritis and polymyalgia rheumatica. AB - The close relationship between giant cell arteritis and polymyalgia rheumatica has not been clearly explained. These disorders affect the same patient population and often coexist in the same person. Monitoring of the erythrocyte sedimentation rate is a useful tool in both diagnosis and treatment. Management with varying doses of prednisone has proved effective in resolving symptoms. PMID- 1738733 TI - Rational treatment of gout. Stopping an attack and preventing recurrence. AB - The most definitive method of diagnosis for acute gouty arthritis is aspiration of the affected joint and examination of the fluid for the characteristic needle shaped monosodium urate crystals. Treatment is aimed at promptly stopping the attack and reversing complications. Colchicine and various nonsteroidal anti inflammatory drugs are effective for both treatment and prophylaxis. Antihyperuricemic therapy may be indicated in patients who have had several attacks in a year. PMID- 1738734 TI - Exercise and the heart. Good, benign, or evil? AB - The risks and benefits of regular aerobic exercise have been studied extensively. Because of the potential risks, we believe that sedentary persons over age 40 who have cardiac risk factors, as well as patients with coronary artery disease (CAD), should have a complete physical examination and probably an exercise electrocardiogram before starting a vigorous exercise program. In general, however, regular exercise has proven to be extra-ordinarily safe and the theoretical and proven benefits appear to greatly outweigh the risks in most people, including those with CAD, those with severe left ventricular dysfunction, and the elderly. PMID- 1738736 TI - Father and son. PMID- 1738735 TI - Acute renal failure in a patient with prostatic carcinoma. A case of benign uropathy. AB - Obstructive uropathy and renal insufficiency are often associated with cancer. However, in the case described here, a patient with carcinoma of the prostate had acute renal failure due to benign obstructive uropathy. Precise, prompt diagnosis and treatment resulted in complete reversal of renal symptoms. PMID- 1738737 TI - Obsessive-compulsive disorder. Characteristic features, pharmacologic management. AB - Obsessive-compulsive disorder is a fascinating and troubling clinical problem that is now believed to be relatively common. New approaches to research are beginning to unlock its secrets and explore its biological underpinnings. Drugs such as fluoxetine hydrochloride (Prozac) and clomipramine hydrochloride (Anafranil) now offer hope for improvement in the lives of affected persons. PMID- 1738738 TI - Acute poisoning emergencies. Resolving the gastric decontamination controversy. AB - As in all medical emergencies, in acute poisoning the cornerstone of management is good supportive care. Aggressive support of the cardiovascular, respiratory, and central nervous systems, along with appropriate gastric decontamination, greatly reduces morbidity and mortality and improves patient outcome. Ipecac is generally reserved for home use, where it can be given to induce emesis immediately after ingestion of toxins, and it is given only in cases of mild or moderate toxicity. Activated charcoal should replace ipecac in the emergency department for cases of mild or moderate toxicity. Gastric lavage and administration of activated charcoal should be considered in cases with life threatening potential. A cathartic should be considered after activated charcoal has been administered, but only in cases where it will not have a detrimental effect. PMID- 1738739 TI - Travel to the Persian Gulf. Medical guidelines for visitors. AB - The disease, destruction, and destitution created by the recent conflicts in the Persian Gulf have resulted in increased international travel to affected countries for relief and reconstruction. Such travel involves more than minimal health risks, but effective preparation of travelers by primary care physicians can help, as discussed by the authors. PMID- 1738740 TI - Surgery in the elderly. Lowering risks by understanding special needs. AB - Elderly patients should be evaluated closely before surgery. Problems commonly found in these patients (ie, hypertension, diabetes, and cardiac and pulmonary disease) should be sought with special care and treated before surgery is undertaken. Also, wound healing may be compromised, drug clearance and metabolism impaired, and nutritional status abnormal. However, if these and other age related problems are anticipated, surgery is usually successful and recovery uneventful. PMID- 1738741 TI - Heart disease after mediastinal radiotherapy. AB - The greatest risk for most cancer patients is inadequate treatment of their disease. Although mediastinal radiotherapy is a safer procedure than it was 20 years ago, it still may damage the thoracic viscera, including the heart. Cardiovascular problems tend to present subtly years later, when the patient may not recall the prior radiation or may not deem it significant. An awareness of this long latency period and of the wide spectrum of heart disease that may result from radiotherapy is essential for management of these patients. PMID- 1738742 TI - Premalignant lesions of the gastrointestinal tract. Surveillance regimens for three treatable disorders. AB - Barrett's esophagus, ulcerative colitis, and adenomatous colorectal polyps have been proven to be precursors of cancer. Early treatment and appropriate esophagoscopic or colonoscopic surveillance for recurrence or disease progression in these patients can save lives. Dr Schuman discusses typical regimens and special considerations in follow-up of these disorders. PMID- 1738743 TI - Pernicious anemia. Early identification to prevent permanent sequelae. AB - Pernicious anemia can be confidently diagnosed in a patient who has megaloblastic hematopoiesis, low serum cobalamin level, and impaired vitamin B12 absorption correctable by administering intrinsic factor. Recent studies suggest that neurologic disorders in patients with pernicious anemia are less severe than in the past, highly responsive to therapy, and seen in the absence of anemia and macrocytosis. A low serum cobalamin level in the absence of anemia, particularly in a patient with a neurologic disorder, should not be ignored. PMID- 1738744 TI - Superficial fungal infections. Topical and oral treatment of common types. AB - Superficial fungal infections are common dermatologic conditions, and patients often visit primary care physicians for evaluation. Diagnosis can be established with direct microscopic examination, fungal culture, and Wood's light examination. Some infections (eg, tinea corporis, tinea cruris, tinea pedis, pityriasis versicolor) are often successfully treated with a topical antifungal alone. Others (eg, tinea capitis, onychomycosis) require use of a systemic antifungal. Physicians should be familiar with available agents and their adverse effects and closely follow patients receiving long-term antifungal therapy. PMID- 1738745 TI - Acute pyelonephritis. Preventing complications through prompt diagnosis and proper therapy. AB - The diagnosis of pyelonephritis is based on clinical and laboratory criteria that include fever, flank pain or tenderness, leukocytosis, pyuria, and confirmatory urine culture. A Gram stain of unspun urine can provide an important early clue regarding the etiologic agent. At least 85% of cases are caused by Escherichia coli, but clinicians need to be aware of other potentially aggressive organisms as well. Elderly, diabetic, or immunocompromised hospitalized patients and patients subject to instrumentation present a more complex diagnostic challenge and require more intense parenteral treatment. Prompt diagnosis and proper therapy decrease the risk of serious complications. PMID- 1738746 TI - Pericarditis and myocarditis. Which is benign and which isn't? AB - Pericarditis and myocarditis are inflammatory diseases that are often initiated by common viruses. Pericarditis rarely causes serious long-term disability, whereas myocarditis may lead to chronic congestive cardiomyopathy and permanent disability. The pathogenesis of both is proposed to be bimodal, with an early stage characterized by viral replication and a later stage by infiltration of lymphocytes and necrosis of cells secondary to an autoimmune process. Treatment of pericarditis is usually symptomatic. Myocarditis requires bed rest and conventional therapy for congestive heart failure. Efficacy of immunosuppressive therapy for myocarditis is currently being tested in an international multi center clinical trial. PMID- 1738747 TI - Oral anticoagulant therapy. Newer indications and an improved method of monitoring. AB - Oral anticoagulants remain time-tested therapeutic agents. A number of new indications for use of these drugs have recently emerged, especially nonvalvular atrial fibrillation. New information on the factors associated with adverse reactions to oral anticoagulants is available, along with improved knowledge on how to evaluate and treat such complications. A major advance in the safer use of these drugs in North America will accompany increased application of the International Normalized Ratio in reporting prothrombin time. PMID- 1738748 TI - $8,334 Concorde flights, bypass surgery, and MRIs. PMID- 1738749 TI - Sorting out the cephalosporins. AB - How can you choose the best cephalosporin to prescribe out of an array that is vast and quickly growing? Dr Brogan simplifies the process by describing the specific advantages as well as the shortcomings of individual agents. He also makes general recommendations based on his experience. PMID- 1738750 TI - Medical school loans. PMID- 1738751 TI - Rethinking the therapeutic pyramid for rheumatoid arthritis. When are NSAIDs alone not enough? AB - A large number of agents that compare quite favorably to nonsteroidal anti inflammatory drugs in terms of toxicity and efficacy are available to physicians for the treatment of rheumatoid arthritis. Primary care physicians need to familiarize themselves with the use of these drugs and consider prescribing them early in the course of the disease, when they may be of greatest benefit. PMID- 1738752 TI - Nonarticular pain syndromes. Differentiating generalized, regional, and localized disorders. AB - Nonarticular pain syndromes, although not inherently crippling, can have significant impact on patients' comfort, daily activities, and job performance. These syndromes include fibromyalgia, bursitis, tendinitis, and localized myofascial pain syndromes. Although differentiating these conditions from one another may be difficult, early diagnosis and follow-up are important for determining appropriate treatment. Depending on the diagnosis, treatment may include use of nonsteroidal anti-inflammatory drugs, analgesics, or corticosteroid injections; trigger-point desensitization therapy; physical therapy; and patient education. PMID- 1738753 TI - Prostanoids as local modulators of reflex micturition. AB - Surge of interest about the possible role of prostanoids in the regulation of urinary bladder function can be traced back to the early 1970s, after the demonstration that prostaglandin-like material is released in the circulation during or immediately after bladder distension. The discovery that even a mild form of tissue stimulation, such as stretch of smooth muscle cells, releases significant amounts of prostanoids prompted the speculation that locally generated prostaglandins (PGs) might aid the receptive functions of hollow organs, such as the stomach and the urinary bladder, thereby allowing accommodation of their physiological content. While the latter interpretation turned out to be incorrect for the urinary bladder, these earlier studies attracted the attention of many investigators on the possible role of prostanoids as local modulators of micturition. This topic has been the subject of some recent reviews addressing the effect of prostanoids in regulating motility, blood flow, defence against infection and carcinogenesis in the urinary bladder. The aim of this short review is to re-address the topic of prostanoid modulation of reflex micturition with particular emphasis on a target for prostanoid action in the urinary bladder (i.e. sensory nerves) which, until recently, has been somehow neglected. PMID- 1738754 TI - Fractal dimension in pharmacology. PMID- 1738755 TI - Membrane antiperoxidative activities of D-propranolol, L-propranolol and dimethyl quaternary propranolol (UM-272). AB - With the isolated sarcolemmal membrane model, the antiperoxidative activities of D-propranolol, L-propranolol and the non-beta-blocker analogue UM-272 (dimethyl quaternary propranolol) were compared. Membrane lipid peroxidation induced by the Fe-catalysed, hydroxyl radical producing system (dihydroxyfumarate + Fe3+) was assessed by MDA formation. In the range of 10-200 microM, both D- and L propranolol exhibited identical concentration-dependent inhibitory effects (20 70%), whereas UM-272 was about 2/3 as active as propranolol. In contrast, lignocaine (lidocaine), a well known membrane stabilizer, did not produce any effect. When purified rat hepatic microsomes were peroxidized by NADPH + Fe3+, comparable antiperoxidative effects were produced by the propranolol enantiomers and the dimethyl analogue. Thus, the antioxidant activities of these agents are related to their intrinsic chemical properties which might contribute to the reported beneficial effects of propranolol and UM-272 in models of ischaemia/reperfusion injury. PMID- 1738756 TI - Influence of cetiedil on erythrocyte membrane microviscosity and acetylcholinesterase activity. AB - Since one of the cellular targets of cetiedil, a vaso-erythroactive drug, is likely to be the erythrocyte membrane, we have studied the influence of this drug on erythrocyte membrane microviscosity and acetylcholinesterase activity. No effect was evidenced on microviscosity, as measured by fluorescence polarization of light emitted by DPH or TMA-DPH labelling of the lipid bilayer. Cetiedil, however, did lower acetylcholinesterase activity, but it did not directly inhibit this enzyme activity. It can therefore be considered as an amphiphilic drug that perturbs membrane properties without affecting the physical state of the erythrocyte membrane. PMID- 1738757 TI - Debrisoquine oxidation in an Italian population: a study in healthy subjects and in schizophrenic patients. AB - The debrisoquine oxidation phenotype was assessed in 137 healthy Italian volunteers and in 41 drug-free schizophrenic patients. A bimodal distribution of the urinary debrisoquine/4-hydroxydebrisoquine metabolic ratio was observed in healthy volunteers. Ten subjects were identified as poor metabolizers, yielding a frequency of 7.3% which is similar to that reported in other European countries. The prevalence of the poor metabolizer phenotype was 9.8% among schizophrenic patients. This indicates that there is no association between polymorphic drug oxidation and schizophrenic disorder. Treatment with chlorpromazine (100 or 150 mg daily) significantly increased the debrisoquine metabolic ratio in nine patients (P less than 0.01). These results confirm that neuroleptics of the phenothiazine class inhibit the oxidative metabolism of debrisoquine. PMID- 1738758 TI - Hepatic uptake and biliary secretion of bile acids in the perfused rat liver. AB - Hepatic uptake and biliary secretion have been evaluated in the isolated perfused rat liver for cholic, chenodeoxycholic, ursodeoxycholic acid, both free and taurine-conjugated; the physicochemical properties of the bile acids have also been calculated and related to these experimental parameters. Cholic acid disappearance rate from the perfusate was the fastest, followed by that of ursodeoxycholic and chenodeoxycholic; it was also faster for taurine-conjugated bile acids than for their respective unconjugated forms. The recovery in bile was higher for conjugated than for unconjugated bile acids, and among each class, was higher for cholic than for chenodeoxycholic and ursodeoxycholic. The hepatic uptake correlated negatively (r = -0.99) with the bile acid lipophilicity, while the biliary secretion correlated with the solubility of the molecules. These results show the effect of the physicochemical properties of BA on their hepatic handling, at the physiological concentration of BA in the portal blood. PMID- 1738759 TI - Treatment with low dose metformin in patients with peripheral vascular disease. AB - Low dose metformin (500 mg b.i.d.) was tested in 11 patients with symptomatic peripheral vascular disease (PVD) in an open design. At -1, 0, 1, 4, 7 months the major lipid and lipoprotein parameters, arterial function, and fibrinolytic activity were monitored. Arterial function changes were similar to those found with a high dose (850 mg t.i.d.) metformin but plasma lipids did not change to an appreciable extent. Post-ischaemic blood flow, by plethysmography, rose 30%; the exercise capacity, evaluated by treadmill test, also increased significantly by 105.7% for relative and 53.3% for absolute claudication. Total fibrinolytic activity did not change during the treatment but the antigens of two of the major components of the fibrinolytic system, i.e. t-PA and PAI-1, were significantly reduced at the end of the study. This study gave results quite consistent with those obtained with higher metformin doses, associated with a potentially higher risk of lactic acidosis. PMID- 1738760 TI - Electrophysiological actions of a new antiarrhythmic drug, bisaramil, on isolated heart preparations. AB - Electrophysiological effects of bisaramil--a new antiarrhythmic drug under clinical trial--were investigated on isolated heart preparations, at a concentration range of 2.3-23 x 10(-6) M. Bisaramil dose dependently decreased the maximum rate of depolarization (Vmax), action potential amplitude (APA) and overshoot (OS) both in auricle and in papillary muscle of guinea-pig heart. There was no significant and obvious effect on the duration of the action potential and the resting membrane potential was also unchanged. Bisaramil slowed the spontaneous frequency of pacemaker cells in rabbit sinus node preparation due to its inhibitory effect on slow diastolic depolarization (SDD). Bisaramil was able to inhibit slow Ca(2+)-action potentials induced by isoprenaline on K(+) depolarized papillary muscle. Results obtained with transmembrane current measurements revealed that bisaramil inhibited both fast Na(+)-current and slow Ca(2+)-current in frog sinoauricular fibres at the same concentration. Bisaramil with a mixed mode of the action seems to be a very promising drug. PMID- 1738761 TI - Reproducibility of Wolfe's classification of mammographic parenchymal patterns. AB - BACKGROUND: Inadequate reproducibility of Wolfe's classification of mammographic parenchymal patterns may explain its limited use in clinical and screening practice. If the misclassification of mammographic parenchymal pattern categories is substantial, inconsistencies in study results will occur, which could at least partially explain the frequent inability to replicate Wolfe's findings in studies of breast cancer. In this article, results of a study to determine whether consensus to resolve inconsistencies between raters would improve the level of concordance in mammographic parenchymal pattern categorization and thus help reduce misclassification are presented. METHODS. One hundred consecutive mammograms from a large screening clinic in New York City were classified independently by two expert mammographers on two separate occasions, 8 days apart. Coding was repeated in two consensus conferences several weeks later. Reliability was estimated by computing intraclass correlation coefficients. RESULTS: Initially, the average intraobserver reliability for the four patterns was 0.68 and the interobserver reliability was 0.65. After consensus, reliability improved markedly to 0.88. CONCLUSION: It is concluded that the added complication and cost of consensus ratings will be more than offset by a substantial increase in precision. PMID- 1738762 TI - Mental retardation associated with parental smoking and alcohol consumption before, during, and after pregnancy. AB - METHODS: In an epidemiologic study, parental alcohol consumption and smoking before, during, and after pregnancy were studied as possible risk factors for mental retardation in offspring. The parents of 306 mentally retarded children (cases) and 322 physically handicapped children (referents) were interviewed about their lifestyle habits from 3 months preconception to 6 months postnatal. RESULTS: Odds ratios with 95% confidence intervals were calculated as risk indicators. For fathers who smoked a pipe or cigars, an odds ratio of 2.4 (95% CI: 1.2-5.1) was observed. Maternal alcohol consumption was increased among the case mothers with risk ratios ranging from 1.7 (95% CI: 1.2-2.3) preconception to 1.4 (95% CI:1.0-2.0) during the fetal period. These risks were more pronounced for the mothers who consumed greater than or equal to 3 drinks/day once or twice a week. CONCLUSIONS: This study suggests that paternal smoking and maternal alcohol consumption are risk factors for mental retardation in offspring. PMID- 1738763 TI - Physical activity in Minnesota physicians. AB - METHODS: A survey inquiring about physical activity was mailed to a random sample of 500 physicians who were current members of the Minnesota Medical Association. RESULTS: Overall, 65.6% of the 393 respondents reported performing regular exercise, while 38.2% participated in exercise vigorous enough to be of cardiovascular benefit (at least three times per week, at least 15-30 min per session, and strenuous enough to cause sweating or shortness of breath). Men reported a significantly higher prevalence of regular exercise and cardiovascular exercise than did women. There was no significant relationship between the prevalence of either regular exercise or cardiovascular exercise and age, specialty, the percentage of primary care performed, the number of patients seen per day, or the number of hours worked per week. CONCLUSIONS: The prevalence of physical activity was higher among physicians in this survey compared with levels reported for the general population. PMID- 1738764 TI - Leisure time physical activity: are there black/white differences? AB - BACKGROUND: Behavioral risk factor surveillance survey data collected during 1984 and 1985 in South Carolina were analyzed. METHODS: This article is based on telephone interviews conducted with 2,005 individuals (431 black, 1574 white), mean age, 45.1 years, selected by random-digit dialing. Information on the type, frequency, and duration of leisure time physical activity was used to estimate leisure time energy expenditure (kcal/week) averaged over the previous month. The median level of leisure time energy expenditure differed significantly (all P less than 0.001) by gender (men = 741, women = 421), age (six categories; youngest, 18-29 years = 780; oldest, 70+ = 301), annual household income (four categories; lowest, less than or equal to $10,000 = 300; highest, greater than $35,000 = 870), body mass index (kg/m2, less than or equal to 24.1 = 601, greater than or equal to 30.1 = 180), and race (black = 301, white = 601). RESULTS: Leisure time energy expenditure generally decreased with increasing age and body mass index and increased with increasing levels of education and income among all race/gender groups. Logistic regression analyses revealed that after adjustment for gender (if applicable), age, income, and body mass index, the variable race made a statistically significant contribution to the model, in the total sample (P less than .03) and for women P less than .001), but not for men. CONCLUSIONS: Our results suggest that blacks living in the South, particularly black women, have lower levels of leisure time physical activity compared with their white counterparts after control for several important confounders. PMID- 1738765 TI - Social status and coronary heart disease: results from the Scottish Heart Health Study. AB - Social status has frequently been found to be associated with the prevalence of coronary heart disease. Currently, in developed countries, it seems that the least advantaged social groups are at the greatest risk. This article addresses this issue in the Scottish population, using a cross-sectional sample of 10,359 men and women. Four measures of social status are used: level of education, years of education, housing tenure, and the Office of Population Censuses and Surveys' definition of social class based on occupation. By each of these four criteria, and for both sexes, the least advantaged have a significantly higher coronary heart disease prevalence (P less than 0.01). The odds ratios for housing tenure are highest, being 1.63 and 1.55 for men and women, respectively, comparing those who live in rented accommodation with owner-occupiers. After adjustment for a number of coronary heart disease risk factors, which are possible confounding variables, most, if not all, of the significant effect of education and occupation on coronary heart disease is removed. Housing tenure is still highly significant (P less than 0.001), with odds ratios of 1.48 and 1.45 for men and women, respectively. Smoking and fibrinogen are the most important confounding variables for men, and body mass index, high-density lipoprotein cholesterol, and triglyceride levels, the most important for women. When relationships among the social factors themselves are investigated, housing tenure is found to remove the significant effects of education and occupation in men, and of education in women. No other social factor removes the significant effect of housing tenure (P less than 0.001). Housing tenure in Scotland is thus found to be the most discriminatory measure of social status in relation to coronary heart disease. PMID- 1738766 TI - The Heart Smart cardiovascular school health promotion: behavior correlates of risk factor change. AB - BACKGROUND: A growing awareness of health promotion and positive lifestyle change, coupled with the knowledge that cardiovascular risk has its origins in childhood, has led to the development of health promotion programs in the elementary school. While most school-based programs target specific behaviors or enlist singular intervention modalities, the Heart Smart cardiovascular school health promotion targeted the total school environment with a multidisciplinary approach to prompt the school's varied institutions to implement changes in curriculum, school lunch, and physical education. METHODS: Components of the Heart Smart environmental intervention included: (a) a school lunch program providing cardiovascular healthful food choices, reduced in fat by 30% and in sodium and sugar by 50%; (b) a physical education program promoting personal fitness and aerobic conditioning; and (c) cardiovascular risk factor screening, measuring fasting lipids and lipoproteins, anthropometrics, and blood pressure. Changes in cardiovascular risk factor status, school lunch selections, and exercise performance were compared. RESULTS: Screening participants showed greater improvement in health knowledge than nonparticipants. School lunch choices were successfully altered, and children whose lunch choices were cardiovascular healthful evidenced the greatest cholesterol reduction. Improvements in run/walk performance were related in predicted directions to the overall cardiovascular risk profile. Increases in high-density lipoprotein cholesterol were observed at intervention schools. CONCLUSION: Observations indicate a relationship between behavior change and physiologic changes achieved in a total school health promotion to reduce cardiovascular risk. PMID- 1738767 TI - Does a reduced fat diet cause retardation in child growth? AB - BACKGROUND: A diet low in saturated fat and cholesterol is strongly recommended by the American Heart Association and the National Cholesterol Education Program as a way to prevent coronary heart disease. In addition, the National Cancer Institute has suggested that dietary fat restriction may also prevent the development of some cancers. However, the American Academy of Pediatrics reviewed the same evidence in relation to children and concluded that that major dietary changes recommended for adults should not be prescribed for children. METHODS: In this article, we review the evidence for the detrimental consequences associated with dietary fat restriction for children. Evidence from studies on secular trends, migration, and vegetarian communities suggests minor effects of dietary fat restriction upon growth. In addition, there is some evidence indicating that children who are placed on severe dietary restriction during growth periods may experience growth stunting. Virtually all of the published studies have serious methodological limitations. CONCLUSION: We conclude that dietary fat restriction may have some small, but measurable, effects upon growth. PMID- 1738768 TI - Primary prevention of cardiovascular disease: 3-year intervention results in boys of 12 years of age. AB - BACKGROUND: The intervention group comprised 477 children at the age of 11.8 +/- 0.11 years. The reference group comprised 528 children aged 11.9 +/- 0.12 years. Both groups were drawn on the basis of the selected examination of children from two Moscow districts. The criteria for risk factors involved the upper 5% of the distribution curve for blood pressure, the upper 10% of the distribution curve for cholesterol and triglycerides, the upper 15% of the distribution curve for the Quetelet index, and a positive response to the question on smoking, "Smoke at least once per week or more frequently?" METHODS: The intervention was carried out both among the entire sample population and more intensively among persons with risk factors. It included counseling for children and their parents on rational diet, physical activity, and smoking hazards. Relevant material on health education was disseminated. Follow-up examinations were carried out at 1 and 3 years following baseline measures. RESULTS: The examination at 1 year showed that the children of the intervention district had attained a greater reduction in their levels of total cholesterol, triglycerides, and systolic blood pressure than those of the reference district. High-density lipoprotein cholesterol levels decreased equally in both districts. After 3 years, the effect was retained for cholesterol and systolic blood pressure; the level of high density lipoprotein cholesterol showed a greater reduction in district 2. After 1 year, the increase in the Quetelet index among the intervention sample (district 1) became less. After 3 years of intervention, the smoking accretion rate had decreased by 8.9% in district 1 (intervention) compared with that in district 2 (reference). PMID- 1738769 TI - Cotinine in an ultrafiltrate of saliva. AB - BACKGROUND: We have developed a device for the simplified collection of a prepurified sample of saliva in the mouth. METHOD: The device is based on the principle of an osmotic pump and accumulated about 1.2 ml of an ultrafiltrate of saliva within 8 min. We have investigated the ultrafiltrate for its utility as a biological medium in the evaluation of cigarette smoking status. RESULTS: (a) In 58 matched samples from 13 subjects, the correlation coefficient for the cotinine concentration in the saliva and the ultrafiltrate was 0.95; (b) in matched plasma and ultrafiltrate samples from 27 smokers, the correlation coefficient for the cotinine concentrations was 0.96 with plasma containing 1.2 times the ultrafiltrate mean; (c) in a nonsmoker, elevated cotinine levels could be detected in the ultrafiltrate more than 24 hr after smoking 2 cigarettes, and the pattern of rise and decrease reflected that in whole saliva; and (d) in a habitual smoker; the mean cotinine concentration in the ultrafiltrate was 157 ng/ml (SD +/- 25.7 ng/ml) during a period of smoking 15 cigarettes per day and dropped to a mean of 47 ng/ml (SD +/- 10.5) when smoking was reduced to 5 cigarettes per day; after cessation of smoking, detectable concentrations of cotinine persisted for up to 5 days. CONCLUSION: The device facilitated the aesthetic, noninvasive collection of a biological sample useful in the validation of smoking status. PMID- 1738770 TI - National TV smoking cessation program and contest in Finland. AB - BACKGROUND: In the fall of 1986 the North Karelia Project in cooperation with Finnish TV 2 arranged an eight-part nationwide smoking cessation TV program. The Project, also arranged a smoking cessation contest coinciding with the TV program in cooperation with four major voluntary public health organizations and the national health service. The TV program featured two studio groups of local volunteers: one from Turku (southwestern Finland) and the other from North Karelia, where there was more intensive community support for the activity. RESULTS: Based on a national survey of a representative population sample, the reported viewing rates (at least one part) of the working-age population (15-64 years, smokers and nonsmokers) were 64% in North Karelia, 45% in Turku, and 46% nationally (P less than 0.001). Among smokers who had watched at least one session of the TV program, 7.7% reported to have tried to quit smoking in North Karelia, 4.1% in Turku, and 7.5% nationally. Altogether, 16,089 smokers participated in the contest; again the highest participation rate was in North Karelia. The 6-month success rate among the smokers who participated in the contest was 22% in North Karelia, 18% in Turku, and 17% nationally (P less than 0.05). Men were more likely to succeed in quitting: among men the 6-month success rate was 22% and among women 15% (P less than 0.001). CONCLUSIONS: The results and experiences indicate high viewing and participation and a beneficial cost effect ratio. They also stress the importance of community support activities in enhancing the effects of a media-based health promotion program. PMID- 1738771 TI - Mammography knowledge and intentions among insured women. AB - METHOD. A survey was conducted among 1,113 randomly selected insured state university employees to evaluate knowledge of the American Cancer Society mammography guidelines, awareness of insurance coverage for screening mammograms, previous guideline adherence, and future mammography intentions. RESULTS: The survey, which included two mailings with follow-up phone cells of nonresponders, had a refusal rate of 6%. Respondents were relatively more likely to know the guideline for older age groups; 77% knew the guidelines for women 50+. Over one third of the responders were not aware that their insurance policy covered screening mammograms. For women who had never had a mammogram, insurance knowledge was significantly related to intentions to have a mammogram in the future. Previous screening adherence, as well as future intentions, was positively related to the age of the respondent. The results are contrasted with those of previous studies, and the implications for the content of future breast cancer screening campaigns are discussed. PMID- 1738772 TI - An iterative technique for identifying smoking deceivers with application to the Scottish Heart Health Study. AB - BACKGROUND: The study population consists of 3,977 self-declared nonsmokers for whom complete data on smoking biochemistry were available. Data were obtained from the Scottish Heart Health Study, a random cross-sectional population sample of 40- to 59-year-old men and women. METHODS: Three biochemical markers of smoking (expired-air carbon monoxide, serum thiocyanate, and serum cotinine) are used together to derive optimum cut-points for distinguishing true nonsmokers from self-declared nonsmokers who are smoking deceivers, using an iterative procedure via a computer program. RESULTS: The cut-points derived are, for carbon monoxide, 6 ppm (sensitivity, 0.81, and specificity, 0.94, when compared with the other two biochemical markers combined), for thiocyanate, 63.4 mumol/liter (sensitivity, 0.75; specificity, 0.92), and, for cotinine, 17.5 ng/ml (sensitivity, 0.77; specificity, 0.98). These cut-points are generally lower than those reported previously, primarily because other studies have taken self reported smoking status to be the truth. The presence of deceivers among declared nonsmokers would tend to raise the biochemical levels of this group and hence of the cut-points. CONCLUSION: The prevalence of smoking deception in the Scottish population is low: the frequency of those at or above all three cut-points is 1.2%, at or above two or more (the preferred definition of a smoking deceiver) is 2.2%, and at or above at least one is 16.4%. PMID- 1738773 TI - A comparison of risk assessment models for term and preterm low birthweight. AB - BACKGROUND: Most epidemiological research dealing with the assessment of risk for low birthweight has focused on all low birthweight births. Studies that have attempted to distinguish between term and preterm low birthweights have tended to examine preterm low birthweight, since the risk of perinatal mortality and morbidity is greatest for this group of infants. METHOD: This study uses data from 25,408 singleton births in a 20-county region in North Carolina to identify and compare risk factors for term and preterm low birthweights, and also examines the usefulness of separate multivariate risk assessment systems for term and preterm low birthweights that could be used in the clinical setting. RESULTS: Risk factors that overlap as significant predictors of both types of low birthweight include race, no previous live births, smoking, weight under 100 lb, and previous preterm or low birthweight birth. Age also is a significant predictor of both types of low birthweight, but in opposite directions. Younger age is associated with reduced risk of term low birthweight and increased risk of pattern low birthweight. CONCLUSION: Comparison of all risk factors indicates that different multivariate models are needed to understand the epidemiology of preterm and term low birthweights. In terms of clinical value, a general risk assessment model that combines all low birthweight births is as effective as the separate models. PMID- 1738774 TI - Prescriptions should come with full information. PMID- 1738775 TI - Setting up an 'EPO' system. Management of patients receiving recombinant human erythropoietin. AB - As more people with end stage renal disease are treated with erythropoietin for their anaemia, a well-coordinated system is essential to monitor their response to treatment. This is best achieved by keeping management of the system in the hands of one or two people. PMID- 1738776 TI - How am I doing and where am I going? Individual performance review in staff appraisal. PMID- 1738777 TI - Handwashing: a process of judgement and effective decision-making. AB - It is well-known that regular handwashing is an effective way of reducing cross infection. Healthcare professionals need to be encouraged to evaluate their practice in the light of research-based evidence of their patients' needs, so improvements can be made. PMID- 1738778 TI - A force to promote bonding and wellbeing. Therapeutic touch and massage. PMID- 1738779 TI - A dynamic role that improves the service. Combining triage and nurse practitioner roles in A&E. AB - Increasing attendance in A&E departments has many negative knock-on effects. These can be reduced by introducing a triage system combined with a nurse practitioner role. PMID- 1738780 TI - Sensitivity can break the taboo. Female sexual problems and treatment approaches. PMID- 1738781 TI - Professional development brings specialist knowledge. The role of the diabetes specialist nurse: the Manchester model. AB - People with diabetes are at risk of a range of complications, but this risk can be significantly reduced by effective management of their condition. A multidisciplinary team approach ensures all aspects of their care, management and education are covered. PMID- 1738782 TI - Data systems can boost nursing care. Nurse management information systems in resource management. AB - Resource management aims to improve patient care by matching resources with patient needs. Nurse management information systems provide data on skill mix, rostering requirements, ward costs and patient dependency levels, enabling a nursing strategy to be planned for the ward. PMID- 1738783 TI - An informed approach may prevent loss. New perspectives on cot death. AB - Cot death can be devastating for both parents and healthcare professionals, causing feelings of helplessness and loss. Recent research, however, has identified some contributory factors, which nurses and midwives can bring to parents' attention. PMID- 1738784 TI - Innovation encourages a broader view. District nurse involvement in student nurse training. AB - As Project 2000 becomes established, district nurses will need to expand their teaching role. Students on community placements can find it difficult to become involved in this one-to-one nursing role, but adequate planning and use of teaching aids can ensure they get valuable insights. PMID- 1738785 TI - A lost world within the shadows. PMID- 1738786 TI - Do autoreceptors mediate dopamine agonist--induced yawning and suppression of exploration? A critical review. AB - The hypothesis that stimulation of dopamine autoreceptors is the mechanism by which dopamine agonists induce yawning and suppression of exploration is critically examined. It is shown that the relation between reduced extracellular dopamine levels, assessed by microdialysis, and behavioural effects of dopamine agonists, a dopamine synthesis inhibitor and a granule storage blocker is highly inconsistent. The time-course and duration of the behavioural effects of dopamine agonists differ from the reduction of extracellular dopamine. Amphetamine cotreatment is shown to increase dopamine levels, while yawning and suppression of exploration can still be induced. The data strongly indicate that autoreceptors are not the mediators of these behavioural effects. It is proposed that postsynaptic receptors mediate dopamine agonist induced yawning and suppression of exploration. Evidence is also presented showing that yawning and suppression of exploration are not functionally equivalent. PMID- 1738787 TI - Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience. AB - Recent studies have shown that brief exposure to an elevated plus-maze (EPM) produces non-opioid antinociception in male mice. The present experiments were designed to assess the effects of diazepam on this phenomenon. When acutely administered, low doses (0.5-1.0 mg/kg) of diazepam failed to produce an anxiolytic profile and exerted rather inconsistent effects on EPM-induced elevations in tail-flick latencies. In EPM-experienced mice, chronic treatment with higher doses of diazepam (2-4 mg/kg, 8 days) produced a weak anxiolytic action and inhibited the early phase of EPM antinociception only. However, in EPM naive mice, 8-day diazepam pretreatment exerted a marked anxiolytic effect and completely eliminated the antinociceptive response to the maze. Together, these data support the view that anxiety is a key factor in certain forms of adaptive pain inhibition and suggest a possible mediational role for benzodiazepine receptors. Our findings also show that prior exposure to the EPM, rather than chronic handling/injection, greatly reduces the anti-anxiety effect of diazepam. Furthermore, since re-exposure to the maze, per se, decreased time spent on the open arms and central platform, a shift in behavioural baseline ("retest anxiogenesis") may have contributed to the weak behavioural effects of diazepam in test-experienced animals. Importantly, as chronic treatment with diazepam did not influence this anxiogenic-like retest profile, our data suggest that a single prior experience of the EPM may radically alter the nature of the anxiety reaction provoked by this test. PMID- 1738788 TI - Different effects of serotonin (5-HT) uptake blockers in caudate nucleus and hippocampus of the rabbit: role of monoamine oxidase in dopaminergic terminals. AB - Slices of rabbit hippocampus or caudate nucleus were incubated with [3H]-5-HT (0.1 microM, 60 min) or with [3H]-DA. In hippocampal tissue, the 5-HT uptake blockers chlorimipramine, fluvoxamine, and 6-nitroquipazine (0.1, 1, 10 microM) reduced the percentage content of [3H]-5-HT in a concentration dependent manner. The degree of inhibition of [3H]-5-HT content produced by the 5-HT uptake inhibitors was not affected by the MAO inhibitors pargyline or amezinium (which by themselves enhanced [3H] loading) or the catecholamine uptake inhibitor nomifensine (which by itself did not affect [3H] loading). In caudate nucleus tissue, however, the [3H]-5-HT accumulation was reduced only at the highest concentration of the 5-HT uptake blockers (10 microM). In the additional presence of the MAO inhibitors or nomifensine (which by themselves increased or diminished, respectively, the [3H] labelling) the 5-HT uptake inhibitors became more potent in reducing the percentage [3H]-5-HT accumulation of caudate nucleus slices. These results indicate (1) that a false labelling of [3H]-5-HT into dopaminergic terminals in the caudate nucleus can be prevented by nomifensine, (2) that the 5-HT uptake blockers seem to accumulate within the dopaminergic terminals, where they may display a MAO inhibitory property. The 5-HT uptake blockers were ineffective on the percentage tritium accumulation of caudate nucleus slices incubated with [3H]-DA, regardless of the presence of pargyline or nomifensine. Tritiated DA and deaminated [3H]-metabolites were separated in the superfusate of [3H]-DA-release experiments in caudate nucleus tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738789 TI - Effect of peripheral administration of cinnarizine and verapamil on the abstinence syndrome in diazepam-dependent rats. AB - The effects of two calcium channel blockers (verapamil and cinnarizine) were evaluated on diazepam withdrawal symptoms. Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg IP for 3 weeks. On abrupt termination of the drug, animals showed withdrawal hyperactivity that was assessed by autonomic, behavioural and motor signs. The peak effect was seen 3 days after the withdrawal of diazepam. On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity. Cinnarizine in higher doses (20 and 40 mg/kg) was found to be effective in suppressing the behavioural signs but verapamil did not show any protective effect against startle response and irritability. These results suggest that modulation of the calcium influx in the CNS might influence withdrawal. PMID- 1738790 TI - Noradrenergic receptor mechanisms in neophobia. AB - We have previously demonstrated that depletion of forebrain norepinephrine (NE) led to an attenuation of neophobia in a novel environment, as defined by a greater preference for novel food over familiar food. To study further the role of forebrain NE in neophobia we chronically infused noradrenergic receptor ligands or forskolin into the lateral ventricles of sham and 6-hydroxydopamine dorsal bundle lesioned rats. Chronic NE infusions into lesioned animals reversed the lesion-induced shift in relative food preference. The beta receptor agonist isoproterenol had moderate effects similar to those of NE in lesioned and sham animals. Phenylephrine, an alpha-1 agonist, was without effect. Forskolin, an adenylate cyclase activator, mimicked the effects of NE infusions. These data suggest a role for noradrenergic stimulation of adenylate cyclase in neophobia. PMID- 1738791 TI - Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats. AB - Amnesia can be induced in rats in the passive avoidance paradigm by administration of scopolamine, a central muscarinic receptor antagonist. Tacrine or galanthamine, inhibitors of acetylcholinesterase, given in conjunction with scopolamine partially reversed the scopolamine-induced deficit in passive avoidance performance. Four so-called cognitive enhancers, all widely used for the treatment of the symptoms associated with mental aging, cerebral insufficiency and senile memory disorder, were investigated in this paradigm. Piracetam, an extract of Ginkgo biloba, dihydroergocristine and a combination of raubasine with dihydroergocristine, all attenuated the amnesia induced by scopolamine. In contrast, nicergoline had no significant effect. Raubasine alone also failed to significantly attenuate scopolamine-induced amnesia, although some doses of raubasine had a non-significant tendency (P less than 0.10) to reduce the amnesia. PMID- 1738792 TI - Twenty-four-hour monitoring of heart rate, motor activity and smoking behavior including comparisons between smokers and nonsmokers. AB - The present study was an attempt to monitor continuously and in parallel cigarette consumption, heart rate, and physical activity under field conditions. In a first experiment the test-retest reliability of the recording devices was evaluated with a small number of nonsmoking students on days with similar schedules. The intraday development of heart rate and activity revealed a remarkable intraindividual stability, and the test-retest reliability coefficients calculated between the totals of heart rate and activity revealed values of 0.73 and higher for heart rate and 0.47 and higher for activity on comparable days. The second experiment was done with housewives as subjects to see whether heart rate and/or activity might differentiate smokers from nonsmokers in subjects who are less strictly bound to a fixed daily work program. The smoker/nonsmoker comparisons revealed significantly higher heart rates for smokers but almost identical activity readings. In a third experiment it was tested whether partial smoking abstinence in the morning might differentiate the morning and afternoon heart rates in smokers. Heart rate but not activity was significantly decreased during the abstinence period. Taken together, the simultaneous monitoring of heart rate and activity might be a valuable instrument in smoking research, since it is sensitive enough to detect manipulations of the smoking behavior under natural conditions. PMID- 1738793 TI - Effects of nicotine on hunger and eating in male and female smokers. AB - We tested whether the inverse relationship between smoking and body weight may be due in part to nicotine's acute effects on reducing hunger and eating. On four mornings, male and female smokers (n = 10 each), abstinent overnight from smoking and food, received one of three nicotine doses (7.5, 15, and 30 micrograms/kg) or placebo (0) via nasal spray every 30 min for 2 h. Self-reported hunger and satiety ("fullness") and craving for cigarettes were obtained after each dose presentation. Subjects subsequently ate ad lib from a large array of food items varying in sweet taste and fat content. For both males and females, nicotine had no effect on self-reported hunger, but cigarette craving was decreased. Rather than being decreased, caloric intake during the meal was unexpectedly increased following nicotine compared with placebo. Cigarette craving increased after the meal, and this increase was unaffected by nicotine dose. There were virtually no differences between males and females in any effects of nicotine. These results indicate that nicotine may not acutely suppress appetite in fasting smokers and suggest that other actions of nicotine or smoking may account for the lower body weights of smokers. PMID- 1738794 TI - Smokeless tobacco abstinence effects and nicotine gum dose. AB - There were two experiments on abstinence from smokeless tobacco. The purpose of the first experiment was to determine abstinence effects from smokeless tobacco. The purpose of the second experiment was to examine the effects of different doses of nicotine gum on smokeless tobacco abstinence effects. The subjects were male Copenhagen smokeless tobacco users who underwent 3 days of baseline measurement while continuing to use smokeless tobacco ad libitum, and 5 days of the experimental condition. In the first experiment, the subjects were assigned randomly to one of two groups and compared: continuous smokeless tobacco users (n = 10), and deprivation plus no nicotine gum (n = 10). In the second experiment, subjects were assigned randomly and in a double-blind fashion to one of three groups and compared: (1) deprivation plus 0 mg nicotine gum (n = 20); (2) deprivation plus 2 mg nicotine gum (n = 20); and (3) deprivation plus 4 mg nicotine gum (n = 20). The first experiment showed significant increases upon abstinence for the following variables: (1) craving; (2) difficulty concentrating; (3) restlessness; (4) excessive hunger; (5) eating; (6) reaction time; (7) variability of reaction time and (8) total withdrawal scores for both the self-rated and the observer-rated forms. The second experiment showed that nicotine gum failed to significantly reduce smokeless tobacco abstinence effects, although those with high cotinine levels may receive some benefit from nicotine gum. PMID- 1738795 TI - Low doses of oxytocin facilitate social recognition in rats. AB - Social recognition of juveniles by adult male residents has been shown to be modulated by neurohypophyseal hormones. The decrease of social investigation behavior during a second encounter with the same juvenile serves as index for social recognition. In the present study it was found that low doses (0.09-6.0 ng.kg-1) of oxytocin (OXT) given subcutaneously dose dependently facilitated social recognition. The effect of OXT appeared specific, since no change in social investigation was found when a novel juvenile was tested during the second encounter. No disturbances of social recognition by the low doses of OXT could be detected, in contrast to higher doses of this hormone. Other neurohypophyseal hormones, vasopressin and vasotocin, did not facilitate social recognition when tested in the same range of low doses. PMID- 1738796 TI - The McCollough effect as a measure of central cholinergic activity in man. AB - The McCollough Effect (ME) is an orientation contingent colour after-effect which has been proposed as an indicator of central neurotransmitter activity. Shute (1979) suggested that the ME could reflect a hippocampal "forgetting" mechanism which should be inhibited by GABAergic neurones and stimulated by cholinergic neurones. The purpose of the present study was to demonstrate that the ME is in fact sensitive to cholinergic and anticholinergic drugs and to compare its sensitivity to more conventional tests of psychomotor and cognitive function. Ten healthy subjects received single doses of physostigmine (0.75 mg SC), hyoscine (1.2 mg), temazepam (20 mg), flecainide (200 mg) or placebo in a double-blind double-dummy presentation. Subjects were tested on a battery of psychomotor and cognitive function tests at baseline and 1 h, and adapted to the ME at 1.5 h. Visual analogue rating scales and conventional tests of psychomotor function and saccadic eye movements indicated that both subjective and objective measures of arousal were impaired by temazepam. The subjective, but not the objective, measures of arousal were also impaired by both hyoscine and physostigmine, but not by flecainide. Initial strength and duration of the ME were decreased by physostigmine and increased by hyoscine and temazepam, relative to placebo (P less than 0.01). Thus, the ME is capable of detecting cholinergic, anticholinergic and GABA mimetic drug effects in man, in therapeutic doses. PMID- 1738797 TI - Effects of single and repeated doses of theophylline on aspects of performance, electrophysiology and subjective assessments in healthy human subjects. AB - The effects of both single and repeated doses of theophylline were evaluated on a battery of nine performance tests, the EEG, the EMG and on subjective assessments of mood and side-effects. The subjects were 20 healthy adults who participated in both phases of this randomized, double-blind, placebo controlled, crossover study. The single dose of 400 mg and the repeated doses of 300 mg b.d. for 4 weeks were intended to attain therapeutic serum concentrations. The Sternberg Additive Factors Method for assessing information processing revealed enhanced performance in both phases of this study, while the Horizontal Addition Test showed improved performance in the single dose phase only. The remaining seven performance tests failed to show significant differences between theophylline and placebo. Single doses of theophylline did not significantly alter mood, but marked adverse effects were encountered in the repeated dose phase, possibly related to unpleasant side-effects. Both EEG and EMG findings indicative of stimulation were associated with a single dose of theophylline, but substantial tolerance developed during 4 weeks of therapy. These findings demonstrate CNS stimulation by both single and repeated doses of theophylline with the occurrence of adverse side-effects during repeated administrations. PMID- 1738798 TI - Panic disorder--a national problem, a federal response. PMID- 1738799 TI - HIV-infected men's practices in notifying past sexual partners of infection risk. AB - The researchers studied the self-reported practices of men infected with the human immunodeficiency virus (HIV) in Los Angeles concerning notifying past sexual partners of their risk of infection. The sample of 111 men consisted of 87 Hispanics, 14 whites, 9 blacks, and 1 Asian. Ninety-three percent identified themselves as homosexual or bisexual, and 13 percent reported having injected a nonprescription drug. Seventy-five percent had tested HIV seropositive within the previous 8 months. Subjects were asked about notifying sexual partners with whom they had contact in the 12-months before the subject tested HIV seropositive. Of the 111 subjects, 39 (35 percent) reported that they had attempted to inform 1 or more past partners. Of those who attempted, 30 subjects (76.9 percent) reported notifying at least 1 partner. Overall, the 111 subjects reported a total of 926 individual sexual partners during the 12 months; 51 partners (5.5 percent) were informed of their risk by the subjects. A multivariate logistic regression analysis indicated that those with the most past sexual partners were least likely to attempt to notify any partner. The same inverse relationship was obtained for actual notification and may stem in part from the greater frequency of nonidentifiable partners among those reporting many encounters. The extent and quality of posttest counseling regarding partner notification was not assessed. However, rates of attempted notification were nonsignificantly higher among those who received private professional counseling, who belonged to a support group, or who received social support from family or friends. The data suggest that without concerted and culturally appropriate counseling, many HIV infected persons do not attempt to notify past sexual partners of their risk. PMID- 1738800 TI - Pilot study of AIDS risk in the general population. AB - This study evaluated a methodology for obtaining information on the prevalence of risk behaviors for human immunodeficiency virus infection (HIV) in the general population. From two census tracts in an upper midwestern urban community, 334 households were identified at random. One adult between the ages of 18 and 55 years in each household was asked to complete a confidential questionnaire about knowledge and attitudes toward acquired immunodeficiency syndrome (AIDS) and risk behaviors for HIV infection. Half the responders were also asked to provide a blood sample for HIV serotesting. Response rates to the behavior questionnaire were high (85 to 90 percent). However, only 72 percent of those asked to provide a blood sample agreed to do so. Survey results showed low rates of HIV risk behavior in this population sample. The median number of lifetime sexual partners was five for men and three for women, and most reported contacts exclusively with persons of the opposite sex. Eleven percent of the men and 5 percent of the women reported having had sexual partners of the same sex during their lifetime. Seven percent of men and 3 percent of women reported same sex partners in the last 12 months. Very few reported extremely high-risk behaviors (that is, only one man reported multiple sexual partners with anal intercourse in the previous year). About one in five survey respondents reported having changed his or her behavior because of the AIDS epidemic, usually by being more selective about and reducing the number of sexual partners. Success of the methodology employed in this survey gives reason for optimism that population-based surveys of behavioral risks for HIV infection are feasible. PMID- 1738801 TI - Public health week: marketing the concept of public health. AB - The Public Health Programs and Services (PHP&S) Branch of the Los Angeles County Department of Health Services began a strategic planning effort in January 1986 to meet new disease trends, curb rising health care costs, consolidate limited resources, and handle shifting demographics. A strategic plan was designed to assess the opportunities and challenges facing the agency over a 5-year horizon. Priority areas were recognized, and seven strategic directives were formulated to guide PHP&S in expanding public health services to a changing community. Health promotion was acknowledged as a critical target of the strategic planning process. Among the most significant results of the health promotion directive was the establishment of an annual Public Health Week in Los Angeles County. Beginning in 1988, 1 week per year was selected to enhance the community's awareness of public health programs and the leadership role PHP&S plays in providing these programs to nearly 9 million residents of Los Angeles County. Events in Public Health Week include a professional lecture series and the honoring of an outstanding public health activist and a media personality who has fostered health promotion. Other free community activities such as mobile clinics, screenings, and health fairs are held throughout the county. With intensive media coverage of Public Health Week, PHP&S has been aggressive in promoting its own services and accomplishments while also educating the community on vital wellness issues. The strategic methodology employed by PHP&S, with its emphasis on long-range proactive planning, is receiving national recognition and could be adopted by similar agencies wishing to enhance their image and develop unique health promotion projects in their communities. PMID- 1738802 TI - Use of restraint devices to prevent collision injuries and deaths among welfare supported children. AB - Evidence that death and injury rates for young children involved in automobile collisions could be reduced if children were restrained prompted the State of Tennessee to pass the nation's first child passenger law, a law that became effective in January 1978. Although similar laws have now been enacted throughout the United States, usually restraint devices are not provided to low-income groups who may have difficulty affording them. Few studies have examined the use of such devices by welfare recipients. A total of 56 black women, receiving Medicaid and residing in inner city Memphis, were interviewed about their use of passenger restraints during automobile travel for their children ages 0-3 years. About two-thirds of the mothers interviewed said they rarely or never used child passenger restraint devices when transporting their child. Children age 3 years were significantly less likely to be transported in child restraint devices than younger children. Women who had received welfare payments for 3 years or more or who made fewer than one automobile trip a week with their child were significantly less likely to use child passenger restraints. These results suggest that, in spite of child passenger laws, automobile restraint devices are not used for a high percentage of children ages 0-3 years receiving medical care under State and Federal Medicaid programs. Since treatment costs are paid under these programs when children are injured in collisions, program administrators may have strong incentives to increase the proportion of these children being restrained while traveling in motor vehicles. PMID- 1738803 TI - Developing cancer control capacity in state and local public health agencies. AB - In 1986, the National Cancer Institute began a major grant program to enhance the technical capabilities of public health departments in cancer prevention and control. This effort, commonly referred to as "capacity building" for cancer control, provided funding to support eight State and one local health department. The program focused on developing the knowledge and skills of health department personnel to implement intervention programs in such areas as smoking cessation, diet modification, and breast and cervical cancer screening. The grants ranged from 2 to 5 years in length, with funding of $125,000 to $1.6 million per grant. The total for the program was $7.4 million. While the priorities set for these grants were nominally similar, their capacity building activities in cancer prevention and control evolved into unique interventions reflecting the individual needs and priorities of each State or locality. Their experiences illustrate that technical development for planning, implementing, and evaluating cancer prevention and control programs is a complex process that must occur at multiple levels, regardless of overall approach. Factors found to contribute to successful implementation of technical development programs include* commitment of the organization's leadership to provide adequate support for staff and activities and to keep cancer prevention and control on the organizational agenda,* the existence of appropriate data to monitor and evaluate programs,* appropriately trained staff,* building linkages with State and community agencies and coalitions to guide community action,* an established plan or process for achieving cancer control objectives,* access to the advice of and participation of individual cancer and health experts,* an informed State legislature,* diffusion of cancer prevention and control efforts,and* the ability to obtain funds needed for future activities. PMID- 1738804 TI - A million dollar measles outbreak: epidemiology, risk factors, and a selective revaccination strategy. AB - Between February 8 and April 4, 1986, an outbreak of measles occurred in the State of Arkansas. A total of 489 suspected measles cases were reported from 53 counties; 86 schools statewide reported suspected measles cases. There were 284 cases confirmed in 18 counties; 23.6 percent among students in one university and 41.2 percent among students in kindergarten through 12th grade in 32 schools. An epidemiologic investigation was carried out to evaluate risk factors for vaccine failure and to assess the effectiveness of a selective revaccination strategy in the outbreak setting. A cohort study conducted at a junior high school showed that, compared with students vaccinated against measles at ages 15 months or older, those vaccinated at ages 12-14 months had a three-fold increased risk of measles (relative risk 3.2, 95 percent confidence interval 1.5, 6.9). For schools reporting measles, the Arkansas Department of Health and the Department of Education jointly required reimmunization of students vaccinated at ages younger than 15 months and the exclusion of students not vaccinated at ages 15 months or older until they were vaccinated or until 2 weeks after the last rash onset. To implement these recommendations, more than 100,000 doses of combined measles mumps-rubella vaccine were distributed at a cost greater than $1 million. PMID- 1738805 TI - Healthy children ready to learn: an essential collaboration between health and education. AB - The "Healthy Children Ready to Learn" initiative starts with the underlying concept that health is a critical partner to optimum education. All children have a right to be healthy. At a minimum, this right assumes promoting optimum use of available and effective preventive measures, such as ensuring compliance with immunization recommendations; promoting measures to prevent injuries; ensuring opportunities to identify disease and disabilities early; and providing prompt treatment when needed. Families must receive the support and assistance they need to raise healthy and educated children. Activities directed toward National Education Goals and the related National Health Promotion and Disease Prevention Objectives can advance progress toward school readiness, focus attention and available resources on needed programs and services, and thus help the nation in achieving its goal of having all children arriving at school each day healthy, well nourished, and ready to learn. To realize these goals and objectives, the two critical systems of greatest importance to children, those providing health services and education, need to collaborate, not only among themselves, but also with social services. A range of critical health problems will require our attention if the goals are to be met, such as availability of prenatal care, infant mortality, inadequate nutrition during pregnancy or early childhood, or both, disease prevention by immunization, infants who have been exposed to drugs, fetal alcohol syndrome, and the emotional and mental disorders of early childhood, to name a few. At any one time, any family may be in need of appropriate services. To address the health and well-being of their young children, a continuum of appropriate, accessible services must be available in the community. The first steps toward successful achievement of the readiness goal will require the identification of health, education, and social service programs that serve young children and their families, and the creation of a climate that fosters innovative and effective collaboration between programs at the Federal and State levels, especially as it pertains to the community. Policies and programs should be built around the needs of families. In this regard, the critical role that parents play in shaping a healthy environment conducive to school readiness must be recognized as a key element in shaping the strategies that should help in achieving the readiness goal. Similarly important is the need to engage professional organizations and other private sector groups involved with health, education, and other children's issues to work with government and families to achieve the school readiness goal and its related health objectives. PMID- 1738806 TI - The role of data-driven planning and coalition development in preventing cardiovascular disease. AB - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Effective programs for the prevention and control of CVD need to include data-based planning and evaluation at the State and local levels. The authors describe the development of data-driven planning and intervention strategies in Missouri. Statewide planning activities have resulted in the formation of an advisory committee and development of a State plan, a resource directory, and training courses. Analysis of mortality data revealed an unusual concentration of CVD deaths in the southeast portion of the State. Local coalitions are being developed in each of six counties in this region to reduce the prevalence of CVD risk factors. A regional behavioral risk factor survey of 1,006 adults identified key risk factors that will be addressed by the coalitions. These data suggested that physical inactivity, obesity, and hypertension are especially acute problems in the area. Key components of the local coalition development included providing localized data and obtaining the strong commitment of the local health departments. Expanded use of chronic disease surveillance data for planning and evaluation will increase the probability that localities, States, and the nation will achieve Year 2000 Health Objectives. The data-based planning process is described as a possible model for use by other States and localities. PMID- 1738807 TI - Geriatric education centers address medication issues affecting older adults. AB - Serious problems have been identified in the prescribing of medications for elderly patients and use of prescription and nonprescription drugs by older persons. Overuse, underuse, and inappropriate use of drugs by the elderly have been widely documented, and the harmful consequences have been described. This paper reviews information concerning the need for action to improve health professionals' knowledge and skills with respect to drugs and the elderly and activities being undertaken by geriatric education centers (GECs) to enhance these capacities. Grant support for the centers from the Health Resources and Services Administration, a Public Health Service component agency, began in 1983. In fiscal year 1992 there are 31 centers operating in 26 States. The centers are multi-institutional and conduct four types of educational activities. These include review of pharmacological issues for multidisciplinary groups, specialized training for pharmacists, discipline-specific programs focusing on medication issues, and activities aimed at educating the public. Examples of the GECs' educational activities are given. PMID- 1738808 TI - Some current factors influencing the prescribing and use of psychiatric drugs. AB - A reprise of selected known factors about the influences affecting the prescribing and use of drugs, and some new developments in the drug marketplace, are the basis for this summary and observations about future expectations regarding psychotherapeutic agents. This information can be used to assist in formulating or updating, or both, conceptualizations and hypotheses for future policy and research planning in this area. PMID- 1738809 TI - A comparison of low birth weight among Medicaid patients of public health departments and other providers of prenatal care in North Carolina and Kentucky. AB - Matching of Medicaid and health department patients' files to birth certificates was used as a means of evaluating the effect of prenatal care given by public health departments on the birth weights of babies of women in Medicaid. Three years of live birth data from North Carolina and 2 years of birth data from Kentucky were used in the analysis. After controlling for other low birth weight risk factors (including the quantity of prenatal care) with logistic regression, women in Medicaid who received prenatal care outside public health departments were found to be substantially more likely than those who received care at health departments to have low weight infants. This association was especially strong for births under 1,500 grams. The authors suggest that the comprehensive prenatal care that is provided by the public health departments, which includes various nonmedical support services, may be responsible for this difference. These findings have important implications for proposed expansions of the Medicaid Program to cover more pregnant women in poverty. PMID- 1738810 TI - Factors associated with rates of participation in WIC by eligible pregnant women. AB - The relationship between sociodemographic, biological, and prenatal care characteristics, and participation rates of pregnant women in the Special Supplemental Food Program For Women, Infants, and Children (WIC) was studied by interviewing 200 postpartum patients in a Buffalo, NY, hospital between October 1988 and January 1989. Among the 136 women eligible for the program, 94 (69 percent) participated during their index pregnancies. WIC participation was found to be highly associated with source of prenatal care and having made more frequent prenatal visits. WIC was related to having fewer children and earlier initiation of prenatal care. Multivariate analysis showed that program participation remained highly associated with the source of prenatal care and the number of prenatal visits, when combined with other factors considered, such as age, education, marital status, number of living children, and timing of initial prenatal visit. The results suggest the need for a WIC enrollment effort directed to providers of prenatal care, who would be urged to encourage women to seek early and adequate prenatal care through the program. PMID- 1738811 TI - Smoking during pregnancy among northwest Native Americans. AB - There is little available information on the smoking habits of Native Americans. The authors used data from the Washington State birth certificate to determine the prevalence of smoking during pregnancy among Native American mothers in Washington State. From 1984 through 1988, 39.8 percent of all Native Americans smoked during their pregnancy. Smoking patterns during pregnancy differed markedly between Native Americans and whites according to maternal age and marital status. The smoking prevalence in Native Americans, adjusted for maternal age and marital status, was 1.3 times higher than that found in Washington State white women. This is the first analysis of statewide smoking rates during pregnancy among Native Americans. The birth certificate can serve as a readily accessible and low cost surveillance system for populations such as Native Americans, who are otherwise difficult to study. Smoking intervention programs need to be targeted at Native Americans, and how their smoking patterns differ from those of the general population needs to be recognized. PMID- 1738812 TI - The multilingual videotape project: community involvement in a unique health education program. AB - The large number of Southeast Asian, Hispanic, and Portuguese immigrants in Rhode Island face formidable language and cultural barriers in gaining access to the health care that they need. As the funding for refugee-specific programs diminishes, the focus is on programs that encourage self-sufficiency, assist in gaining access to mainstream health care, and involve a collaboration among service agencies and the communities they serve. On behalf of a coalition of health care and community agencies, Women and Infants Hospital of Rhode Island received a private foundation grant to produce nine multilingual videotapes that would educate immigrants and refugees about health issues specific to them and help them access the health care system. The project was structured to maximize the involvement of the various communities and to "empower" community members in working with mainstream service agencies. Coalition and other community members provided input into topic selection, script content, and presentation methods for the videotapes that would be culturally appropriate. During the 2-year project, nine videotapes were produced with narration in seven languages. Copies of the videotapes were distributed free of charge to coalition members. PMID- 1738813 TI - Simulating smokers' acceptance of modifications in a cessation program. AB - Recent research has underscored the importance of assessing barriers to smokers' acceptance of cessation programs. This paper illustrates the use of computer simulations to gauge smokers' response to program modifications which may produce barriers to participation. It also highlights methodological issues encountered in conducting this work. Computer simulations were based on conjoint analysis, a consumer research method which enables measurement of smokers' relative preference for various modifications of cessation programs. Results from two studies are presented in this paper. The primary study used a randomly selected sample of 218 adult smokers who participated in a computer-assisted phone interview. Initially, the study assessed smokers' relative utility rating of 30 features of cessation programs. Utility data were used in computer-simulated comparisons of a low-cost, self-help oriented program under development and five other existing programs. A baseline version of the program under development and two modifications (for example, use of a support group with a higher level of cost) were simulated. Both the baseline version and modifications received a favorable response vis-a-vis comparison programs. Modifications requiring higher program costs were, however, associated with moderately reduced levels of favorable consumer response. The second study used a sample of 70 smokers who responded to an expanded set of smoking cessation program features focusing on program packaging. This secondary study incorporate in-person, computer-assisted interviews at a shopping mall, with smokers viewing an artist's mock-up of various program options on display. A similar pattern of responses to simulated program modifications emerged, with monetary cost apparently playing a key role. The significance of conjoint-based computer simulation as a tool in program development or dissemination, salient methodological issues, and implications for further research are discussed. PMID- 1738814 TI - Serum cholesterol concentrations among Navajo Indians. AB - Navajo Indians have been reported by earlier investigators to have low concentrations of serum lipids and a low prevalence of hyperlipidemia, as well as low rates of ischemic heart disease. However, no data on serum lipid concentrations among Navajos have been reported for more than two decades. The authors conducted a study to determine the distribution of concentrations of serum total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride among persons 25-74 years old living in a representative community on the Navajo Indian reservation. Data are reported for 255 subjects, 105 men and 150 women, ages 25-74 years. The authors compared these data to those for the general population as determined by the second National Health and Nutrition Examination Survey (NHANES II). TC concentrations among Navajo men were similar to those from NHANES II. TC concentrations among younger Navajo women were similar to those for women younger than 55 years from NHANES II, but were significantly lower among older Navajo women. While 27.6 percent of men ages 25-74 years studied in NHANES II had TC concentrations greater than 240 milligrams per deciliter, 33.8 percent of Navajo men had similarly elevated TC. However, the prevalence of serum TC concentrations greater than 240 milligrams per deciliter among Navajo women (17.5 percent) was about half that among women studied in NHANES II (32.9 percent). A similar pattern was found for low density lipoprotein cholesterol. The researchers concluded that Navajo Indians are no longer characterized by low serum lipid concentrations, that increased cholesterol concentrations may be a harbinger of increasing rates of atherosclerotic coronary heart disease among Navajos, and that attention should be directed to primary prevention of hyperlipidemia in Navajo Indian communities. PMID- 1738815 TI - Can B-cell signalling be understood? PMID- 1738816 TI - Effects of stress on the growth of a fibrosarcoma in nu/nu and conventional mice. AB - BALB/c mice subjected to water stress twice daily, between 3 and 7 min at each exposure 3 days before, 5 days after, or 3 days before and 5 days after intradermal Meth A tumour transplantation, showed an increase of tumour size and tumour growth rate compared with that of home cage control (HCC) mice. However, BALB/c mice subjected to water stress 3 days before and 6 days after tumour transplantation showed a decrease of tumour size and tumour growth rate compared with HCC mice. BALB/c mice subjected to 2 min of handling stress daily on days 1 through 5, but not BALB/c mice subjected to handling stress on days 1 through 7 or on days 6 through 7 of tumour growth, showed an increased in tumour size relative to HCC mice. On the other hand, BALB/cBy mice handling stressed on days 1 through 7, but not BALB/cBy mice handling stressed on days 1 through 5 or days 6 through 7 after tumour transplantation, showed a decreased tumour size compared with HCC mice. No effect of stress could be observed when nu/nu BALB/c mice were subjected to water stress 3 days before and 6 days after tumour transplantation. However, BALB/c nu/nu mice pre-injected intraperitoneally with spleen cells from conventional mice had a decreased tumour size and growth rate of the tumour when stressed 3 days before and 6 days after tumour transplantation. PMID- 1738817 TI - The complete amino acid sequence of bovine serum amyloid protein A (SAA) and of subspecies of the tissue-deposited amyloid fibril protein A. AB - Bovine serum amyloid A (SAA) was isolated from the acute phase high density lipoprotein (HDL) fraction of a cow suffering from acute mastitis. The elucidated primary structure revealed a protein consisting of 112 amino acid residues. Compared with SAA proteins from other species, the bovine protein was shown to have an insertion of nine amino acid residues between positions 69 and 70. No microheterogeneity could be observed in the protein. Amyloid fibrils extracted from the kidneys were found to contain at least three subspecies of protein AA, consisting of 68, 81 and about 110 amino acid residues. The amino acid sequences established for the protein AA subspecies revealed no microheterogeneity, and were identical to that elucidated for protein SAA. PMID- 1738818 TI - Interferon-gamma production by African swine fever virus-specific lymphocytes. AB - Peripheral blood mononuclear cells (PBMC) from inbred pigs that were immunized with autologous macrophages infected with the African swine fever (ASF) virus BA71V, a nonvirulent virus isolate, proliferated and produced interleukin-2 in response to homologous and heterologous isolates of the ASF virus. They produced, however, interferon (IFN) only when challenged in vitro with homologous or attenuated isolates of the ASF virus, but not with heterologous or virulent isolates. The IFN was pH 2 labile and was neutralized by specific serum to porcine recombinant IFN gamma. PMID- 1738819 TI - [Glucocorticoids and infection]. AB - Glucocorticosteroids are the most commonly used immunosuppressive agents. In the following review important mechanisms of action of glucocorticoids on the immunological network are summarized, the relationship between duration of therapy, daily dose and incidence of infections is analysed, and evidence is presented that in some infectious diseases glucocorticoids may even be beneficial. The association between corticosteroid therapy and subsequent infections was calculated by pooling the data from 73 controlled clinical trials (meta-analysis). The rate of infectious complications was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg prednisone. With increasing doses the occurrence rate of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding which suggests that not only the corticosteroid but also the underlying disease state accounts for the steroid-associated infectious complications observed in clinical practice. To analyze the effect of glucocorticoids prescribed as adjuvants in patients with infectious diseases, an analysis of the controlled trials was performed. Some patients with pulmonary tuberculosis or constrictive pericarditis have a better outcome when they are given prednisone. On the other hand, there is no evidence that patients with septic shock or ARDS derive advantage from glucocorticoid therapy. At present there is controversy as to whether patients with bacterial meningitis should be treated with glucocorticosteroids. Patients with hepatitis B should not be treated with glucocorticoids, whereas elderly patients less frequently show postherpetic neuralgia when given glucocorticosteroids. Patients with cerebral malaria should not be given glucocorticosteroids. Aids patients with pneumocystis carinii pneumonia have a higher survival rate when treated with glucocorticosteroids than with placebo. PMID- 1738820 TI - [Addison's disease in the framework of poly-glandular autoimmune syndromes: 3 case reports]. AB - Case reports of three patients with idiopathic Addison's disease combined with other associated autoimmune endocrine and non-endocrine disorders are presented. In the first patient, a young man with a long-standing history of mucocutaneous candidiasis, latent Addison's disease was discovered by diagnostic screening tests. In the two other patients, women aged 39 and 20 respectively, overt Addison's disease combined with primary hypothyroidism was diagnosed. One of them also had a pre-existing ovarian failure. The polyglandular autoimmune syndromes with Addison's disease are classified into two different subtypes, on the basis of characteristic patterns of disease combinations and on different modes of inheritance. Patients with autoimmune Addison's disease are at relatively high risk for other endocrine disorders or non-endocrine autoimmune diseases. Therefore, these patients--and in some instances also their relatives--need lifelong supervision and advice to ensure timely recognition of any associated diseases. PMID- 1738821 TI - [Toxic shock syndrome in infection due to Streptococcus pyogenes]. AB - Acute infections with group A beta-hemolytic streptococcus normally take a favourable course under therapy with penicillin. Only in a few cases has a completely different manifestation been described with multisystem failure similar to toxic shock syndrome induced by Staphylococcus aureus. We report on 4 patients (1990/91) who showed this manifestation in spite of immediate antibiotic therapy. In 3 patients the suspected portal of entry was the skin, in 1 patient it was unknown. Group A streptococci were grown from blood cultures from all 4 patients. Without an underlying immune deficiency all 4 patients (age 22, 24, 38 and 51) went into septic shock with high fever, hepatic and renal impairment, diarrhea, DIC and cerebral confusion. 2 patients died within a few days after developing acute respiratory distress syndrome and cerebral edema. All strains isolated from the patients were penicillin-sensitive, group A streptococci. 3 of them were M-type 1, which are known to be more invasive. The bacteremia by itself is not sufficient to explain all complications and the high mortality rate. It is probable that streptococcal toxins, such as pyrogenic exotoxin A, streptolysin O, or a new unknown one, play a decisive role. PMID- 1738822 TI - [Pericardectomy and acute infectious pericarditis]. AB - Between 1980 and 1990 12 patients (5 male, 7 female) were operated on for acute infectious pericarditis at a mean age of 42 years. The infections were 6 bacterial (purulent 4, abscess 2), 4 tuberculous, 1 viral and 1 Candida. Pericarditis resulted from contiguous spread of infection from bilateral pneumonia in 3 patients, from subphrenic abscess in 2 and followed bacteremia in 1. Clinical signs were: tamponade/shock in 9, elevated jugular venous pressure in 11, edema in 6, hepatomegaly in 6, ascites in 1, and pericardial friction rub in 3. A preoperative pericardiocentesis in 9 patients allowed only 4 positive microbiological diagnoses and was an insufficient drainage in all cases. The preoperative mean NYHA class was 3.3. The pericardectomy was total in 9 patients and partial in 3. Total mortality was 1/12 patients (8%) with one late death due to recurrent tuberculous pericarditis. No patient with purulent pericarditis died. Another recurrence occurred 6 months after acute viral pericarditis. Atrial fibrillation in one patient was the only postoperative complication. After a mean follow-up period of 48.5 months no cardiac constriction had occurred in 11 surviving patients Actuarial survival after pericardectomy is 100% after 1 month and remains 91% after 5 years. The mean NYHA class has significantly improved to 1.2 (p less than 0.05) at the end of the follow-up. We conclude that pericardectomy combined with a specific antimicrobial therapy is a safe treatment for acute infectious and especially purulent pericarditis with low mortality and excellent longterm results. Early pericardectomy allows rapid decompression of the heart, removal of intrapericardial adhesions and infected tissue and prevents late constriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738823 TI - [Severe accidental hypothermia with cardiopulmonary arrest: prolonged resuscitation without extracorporeal circulation]. AB - We describe a case of severe hypothermia in a 32-year-old patient who fell into a crevasse. Three hours later he was rescued and flown to a district hospital. On arrival he was apparently dead, with cadaveric skin, dilated and fixed pupils, pulseless and in respiratory arrest. His rectal temperature was 26 degrees C. On the ECG monitor there was first ventricular fibrillation, then, after several unsuccessful attempts at defibrillation, the heart became asystolic. Cardiopulmonary resuscitation was begun with orotracheal intubation and external cardiac compression, which eventually lasted 4 hours and continuously required a team of 6 persons. Only at a temperature of 32.5 degrees C could the patient be defibrillated with success. In the absence of extracorporeal circulation (ECC) the victim was rewarmed by warm-air breathing and by instillation of warm saline in peritoneum, stomach and bladder. In this way the rewarming velocity was 1.8 degrees C/hour. The postacute course was characterized by severe rhabdomyolysis (CK of 100,000 U/L) with non-oliguric renal failure, which necessitated several sessions of hemodialysis. Four months later the asymptomatic patient returned to work. Our case shows that a severely hypothermic patient can successfully be treated in a primary hospital not equipped with an ECC, provided that there is a sufficiently large team. Further, uninterrupted external cardiac compression guarantees efficient circulation even over several hours. Electric defibrillation in a hypothermic patient is ineffective unless normal body temperature has been reached. Lastly, every effort to continue resuscitation must be made in the still hypothermic patient whose absence of clinical response may obscure the real possibility of complete recovery. PMID- 1738824 TI - [Concerning "Trainee in internal medicine. Does the future general internist need participation in sciences?" by P.W. Straub (Schweiz. med. Wschr. 1991; 121: 1435 1438)]. PMID- 1738825 TI - [Medicine and animal experiments--some thoughts and facts]. PMID- 1738826 TI - [New procedures for resin-metal bonds. A comparative in-vitro study]. AB - Since 1984 it has been possible to create a chemical bond between dental alloys and composite resins resembling the metallo-ceramic bond. Modern systems based on silanization (Rocatec, Silicoater MD, and Spectralink), in connection with the specific resins used in these systems (VisioGem, Dentacolor, and SR-Isosit-N), were tested for their bond strength to 9 common dental alloys (of 7 different types) with regard to shear strength, the topography of the fracture surfaces, and metallographic microstructure transformations. No major structural transformations were observed for any of the systems tested. A notable degree of interdependence was seen in the Silicoater MD system whose bond strength to non precious alloys (among others) was the lowest in the test. The Rocatec system, on the other hand, showed a superior bond to all types of alloys, especially to pure titanium. PMID- 1738827 TI - Morphological and labeling evidence supporting and extending a modern theory of tooth eruption. AB - As the interest in biological mechanisms of tooth eruption has recently been revived by a new eruption theory, the present study was an attempt to contribute new data to this problem. Four male Macaca fascicularis monkeys, two infant (about 13 months old) and two juvenile (about 44 months old), were labeled either by sequential fluorochrome or by single 3H-proline injections and then served for studying the bone apposition patterns around erupting premolars and molars. About 100 microns thick ground sections cut either in the mesiodistal or bucco-oral direction and the corresponding micrographs, microradiographs and autoradiographs, as well as fluorescence micrographs were used. In the multirooted teeth studied, bone apposition was most prominent and fast in the inter-radicular region, while at the fundus of the alveoli, bone apposition was slight or negligible. Around maxillary premolars and molars, bone apposition pointed in the mesial as well as in the axial direction. This was true for the intraosseous and the supraosseous phase of tooth eruption. Using these observations in addition to preliminary data calculated for the rates of bone apposition in the inter-radicular, apical and crestal regions, and for the rate of root elongation, the new eruption hypothesis could be extended. It is suggested that eruption of multirooted teeth, in the presence of corresponding coronal resorption, is entirely explained by forces generated through inter radicular bone apposition and that their dental follicle is in a stimulating mode inter-radicularly but neutral apically at the bottom of the alveolar fundus. PMID- 1738828 TI - [The optimization of dentin bonding in mixed Class-V cavities]. AB - A new functional bonding agent was tested in the placement of mixed class V in vitro restorations. Variable insertion procedures of the composite material were also evaluated. One of the procedures was the direct filling technique, the other were direct immediate composite inlays, cemented with light, chemically or dual cured composite cements. The quantitative SEM marginal analysis results showed a significant superiority (p less than 0.05) of the adhesive inlay restorative procedure over the direct filling technique. Dye penetration confirmed these findings. Among the inlay groups, postcuring and the curing method of the composite cement were crucial for the success. PMID- 1738829 TI - [Bristle anchoring and bristle end-rounding in adults' toothbrushes]. AB - Scanning electron microscopic study of bristle heads of 8 toothbrush brands commercially available in the Federal Republic of Germany and Switzerland has shown qualitative variations in the rounding of bristle ends. The percentage of acceptable end rounding of the bristles was for 4 brands above 75% and for 2 brands 55-56%. For 2 products, the percentage was below 40%. The new method of welding bristle bundles at their base into the head of the toothbrush was used only by one producer. PMID- 1738830 TI - [Tooth-colored inlays/overlays. Tooth-colored adhesive inlays and overlays: materials, principles and classification]. PMID- 1738831 TI - [The discovery of accessory root canals]. PMID- 1738832 TI - [Formaldehyde and paraformaldehyde allergy. Allergic reactions to formaldehyde and paraformaldehyde after tooth root treatments]. PMID- 1738833 TI - Chronic fatigue syndrome. PMID- 1738834 TI - Alar: the aftermath. PMID- 1738835 TI - Alar: the aftermath. PMID- 1738836 TI - Science budget: selective growth. PMID- 1738837 TI - Sequencing venture sparks alarm. PMID- 1738838 TI - Stepping up the pressure on indirect costs. PMID- 1738839 TI - Sarin indicted. PMID- 1738840 TI - Zagury in the clear. PMID- 1738841 TI - Molecular design gets into a hole. PMID- 1738842 TI - "African Eve" backers beat a retreat. PMID- 1738843 TI - Boring in on beta-amyloid's role in Alzheimer's. PMID- 1738844 TI - On the probability of matching DNA fingerprints. AB - Forensic scientists commonly assume that DNA fingerprint patterns are infrequent in the general population and that genotypes are independent across loci. To test these assumptions, the number of matching DNA patterns in two large databases from the Federal Bureau of Investigation (FBI) and from Lifecodes was determined. No deviation from independence across loci in either database was apparent. For the Lifecodes database, the probability of a three-locus match ranges from 1 in 6,233 in Caucasians to 1 in 119,889 in Blacks. When considering all trios of five loci in the FBI database, there was only a single match observed out of more than 7.6 million comparisons. If independence is assumed, the probability of a five locus match ranged from 1.32 x 10(-12) in Southeast Hispanics to 5.59 x 10(-14) in Blacks, implying that the minimum number of possible patterns for each ethnic group is several orders of magnitude greater than their corresponding population sizes in the United States. The most common five-locus pattern can have a frequency no greater than about 10(-6). Hence, individual five-locus DNA profiles are extremely uncommon, if not unique. PMID- 1738845 TI - Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. AB - In retroviral integration, the viral integration protein (integrase) mediates a concerted DNA cleavage-ligation reaction in which the target DNA is cleaved and the resulting 5' ends of target DNA are joined to the 3' ends of viral DNA. Through an oligonucleotide substrate that mimics the recombination intermediate formed by this initial cleavage-ligation reaction, the purified integrase of human immunodeficiency virus was shown to promote the same reaction in reverse, a process called disintegration. Analysis of a set of structurally related substrates showed that integrase could promote a range of DNA cleavage-ligation reactions. When the viral DNA component of the disintegration substrate was single-stranded, integrase could mediate a DNA splicing reaction analogous to RNA splicing. PMID- 1738846 TI - Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor. AB - The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition. PMID- 1738847 TI - Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. AB - The approximately 120-kilodalton amyloid beta protein precursor (beta APP) is processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives that includes potentially amyloidogenic forms with the approximately 4-kilodalton amyloid beta protein (beta AP) at or near their amino terminus. In order to determine if these derivatives are processed in a secretory pathway or by the endosomal-lysosomal system, (i) deletion mutants that produce the normal set of carboxyl-terminal derivatives and shortened secreted derivatives were analyzed and (ii) the effect of inhibitors of endosomal-lysosomal processing was examined. In the secretory pathway, cleavage of the beta APP occurs at a single site within the beta AP to generate one secreted derivative and one nonamyloidogenic carboxyl terminal fragment, whereas, in the endosomal-lysosomal system, a complex set of carboxyl-terminal derivatives is produced that includes the potentially amyloidogenic forms. PMID- 1738848 TI - Chondroitin sulfate as a regulator of neuronal patterning in the retina. AB - Highly sulfated proteoglycans are correlated with axon boundaries in the developing central nervous system which suggests that these molecules affect neural pattern formation. In the developing mammalian retina, gradual regression of chondroitin sulfate may help control the onset of ganglion cell differentiation and initial direction of their axons. Changes induced by the removal of chondroitin sulfate from intact retinas in culture confirm the function of chondroitin sulfate in retinal histogenesis. PMID- 1738849 TI - Human origins and analysis of mitochondrial DNA sequences. PMID- 1738850 TI - Financing health services in Sub-Saharan Africa: options for decision makers during adjustment. AB - The financing of health services has become an increasingly critical and urgent issue in many developing countries particularly in Sub-Saharan Africa. This paper analyses options available to policy makers. The possible effects and side effects of strategies are described based on the experience from different countries. The dangers of simplistic solutions are discussed. A cautious approach is recommended taking into consideration the lessons learned in other regions accompanied by a careful ongoing evaluation especially regarding the ability to pay of the poorer sections of the population. Providing for equity in health care should be an important guiding principle. It therefore appears to be necessary to find an appropriate mix of public and private sector interventions with elements of cost-sharing for services and drugs, insurance schemes and more efficient use of available resources. PMID- 1738851 TI - Effect of the Holocaust on coping with cancer. AB - The aim of the study was to investigate whether surviving stressful life threatening situations influences coping with new stressful life threatening situations. The study group, therefore, was composed of 53 cancer patients (present life threatening situation) who had survived the Holocaust (past life threatening situation). They were compared to 53 cancer patients who had not gone through the Holocaust, matched for sociodemographic and medical background. The Holocaust survivors were unable to mobilize partial denial (had significantly higher scores on the Impact of Events Scale) and their psychological distress was much higher (significantly higher scores on the Brief Symptom Inventory). Their functioning however (as reported along the Psychosocial Adjustment to Physical Illness Scale) did not significantly differ from that of the comparison group. The possible mechanisms for these long term effects of past trauma are discussed as well as the need to regard traumatized persons as 'high risk' psychologically when they have to cope with new life threatening situations. PMID- 1738852 TI - Time and energy costs of distance in rural life space of Zimbabwe: case study in the Chiduku Communal Area. AB - Time cost of distance (TCD) and energy cost of distance (ECD) devoted to routine activities for supporting the basic human requirements of rural households have become a major source of concern because of the high proportion of the daylight TCDs and ECDs expended on such tasks in most rural areas of Sub-Saharan Africa. The high burden of TCDs and ECDs on members of the rural household has constrained daylight time available for food production and health maintenance. This case study in a Communal Area (CA) of Zimbabwe, examines the total and comparative magnitudes of TCDs and ECDs on trips for domestic chores, social services and tertiary functions (markets, central services, transport and communication), as well as the gender and age differences in the absorption of TCDs and ECDs for these activities. The findings indicate excessive uses of the time and energy budget on walking trips to accomplish basic household necessities in which domestic chores consume by far the largest portion of this budget with the highest burden falling on the female members of the household. PMID- 1738853 TI - Explanation of vigorous physical activity during two years using social learning variables. AB - This study examined determinants of vigorous physical activity in a community sample of adults over a 24-month period. Social learning theory predicts that causal relationships between determinants and behavior are bidirectional, and both the behavior and its influences are subject to change over time. Thus, dynamic variables were expected to account for more variance in exercise change than static baseline variables. Over 86% of respondents to the baseline mail survey completed follow-up surveys 24 months later, yielding a final sample of 1739. Two physical activity change indices were constructed that were adjusted for baseline exercise and demographic variables, so that the effects of social learning variables could be isolated. In a two-step hierarchical regression analysis, physical activity measures were regressed onto 21 static and six dynamic independent variables. Baseline self-efficacy was a significant predictor of exercise change for both dependent variables. Four dynamic social learning variables were significantly associated with both exercise change measures: self efficacy, perceived barriers, family support, and friend support. Social learning variables accounted for 12.3-15.5% of the variance in exercise change over 24 months. The results provide strong support for bidirectional causation between behavior and determinants and suggest hypotheses to be tested in experimental studies. PMID- 1738854 TI - Is magnitude of co-payment effect related to income? Using census data for health services research. AB - This study: (1) describes and evaluates a method for estimating household income using home addresses in conjunction with census data, and (2) uses this method in a study designed to determine if the introduction of copayments caused primary care office visit rates to decrease more for lower income enrollees than for higher income enrollees of a large health maintenance organization (HMO). Each step in the process of linking income estimates for small census units (block groups) to specific home addresses is described and the validity and precision of these estimates is assessed through comparisons of estimated income with self reported income for residents of the Puget Sound area of Washington state. Although subject to considerable measurement error, this approach provided valid income estimates. This method was then used to estimate the incomes of over 20,000 households of HMO enrollees in a controlled study of the relationship between copayment effect on visit rates and enrollee income. Copayments were found to have a similar effect on higher and lower income enrollees. PMID- 1738855 TI - Alcohol problems and sense of coherence among older adults. AB - The relation between alcohol problems and sense of coherence (SOC), a salutogenic model developed by Antonovsky, was assessed on a sample of 952 older members of a health maintenance organization. Data on alcohol problems (5-item index) and SOC (9-item scale) were obtained from mailed questionnaires. Multiple regression analyses indicated that SOC was a significant negative predictor of alcohol problems while controlling for alcohol consumption level, frequency of drunkenness and demographic characteristics. In addition, SOC scores were significantly higher for a subsample of lighter drinkers who reported no alcohol problems in the last year and had not been drunk in the last year (n = 419) as compared to heavier drinkers who reported at least one alcohol problem in the last year, and reported being drunk at least once in the last year (n = 107). These findings emphasize the importance of assessing factors which contribute to healthier behaviors as opposed to focusing exclusively on predictors of pathogenic outcomes. PMID- 1738856 TI - Prevalence of self-reported poor sleep in a healthy population aged 50-65. AB - Many population-based surveys have reported that the prevalence of poor sleep increases with age. Despite the uniformity of findings, it remains unclear to what extent age-related declines in overall physical health are related to those results. One approach to this problem has been to adjust for such confounding variables multivariately. Some prior studies using this approach have not shown the expected age-related increases in the prevalence of poor sleep. Another approach has been the study of sleep in carefully screened, healthy populations. The current study reports the prevalence of disturbed sleep in a population, ages 50-65, carefully screened for physical health as part of an ongoing study of exercise and cardiovascular function. The prevalence of self-reported trouble falling asleep every night or almost every night (1.1% M, 2.6% F), trouble awakening and returning back to sleep (4.4% M, 3.3% F), and use of hypnotic medication at least twice a week (1.6% M, 2.6% F) were consistently lower than in nearly all previous population-based studies of individuals of comparable age. This implies that when overall physical health factors are taken into account a decline in sleep quality is not necessarily an inevitable component of aging per se. As has been shown in other studies, there were small but statistically significant relationships between self-reported depression and poor sleep. Despite the low prevalence of poor sleep, about a third of the population reported feeling not well-rested and/or not getting the sleep they required. The individuals in this study also reported obtaining significantly less sleep relative to normative data from 30 years ago.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738857 TI - Medical specialists' choice of location: the role of geographical attachment in Norway. AB - The relation between current place of work (area of the country) and factors that might possibly represent doctors geographical attachments was studied in a sample of 322 Norwegian medical specialists. Location of hospital residency, age and geographical origin of spouse were associated with current location. Geographical attachment seems to influence doctors' locational choices from start of medical school until the end of their residency. The probability that a doctor shall locate in peripheral areas may increase from less than 10% to more than 50% if the doctor has the residency training in the periphery. Hence, favoring entrance to medical schools of students from the underserved areas, and location of graduate and postgraduate medical training in the underserved areas, as far as it is feasible while still maintaining medical standards, is suggested by the study. PMID- 1738858 TI - African women and AIDS: negotiating behavioral change. AB - Trends in the incidence of HIV/AIDS infection among women in Sub-Saharan Africa suggest this population is increasingly at risk. Many of the same factors that have predisposed rural African women to ill health in the past now increase their vulnerability to AIDS, including poverty and malnutrition, uncontrolled fertility, and complications of childbirth. As men travel out from rural communities to urban centers in search of employment, their sexual contacts multiply; many will acquire the HIV virus and carry it back to infect wives at home. Women, too, are leaving rural areas for the promise of a better life in cities and commercial centers along the way. Their struggle for economic survival and personal autonomy has led many to form relationships with new sexual partners, with a consequent increase in HIV seroprevalence among women once considered at low risk of infection. This paper argues that AIDS prevention campaigns have not yet taken into account the cultural, social, and economic constraints on most African women's ability to comply with advice to limit partners and use condoms. The author proposes a research agenda to explore the meaning of AIDS and AIDS prevention in the sociocultural context of women's lives. A better understanding of how women, themselves, perceive and respond to current attempts to prevent the transmission of AIDS is an increasingly critical factor in the intervention process. Most important, it is a necessary first step toward their effective participation with men in the development of culturally relevant strategies for protecting themselves and their families. PMID- 1738859 TI - Prostitutes and their clients: a Gambian survey. AB - The social backgrounds and working behaviour of 248 prostitutes in urban and rural areas of The Gambia were investigated. Prostitutes were found to be highly mobile, moving frequently between a number of working locations in The Gambia and neighbouring Senegal, from which most of them originated. The educational level of prostitutes and the standard of living of their natal families were above average. Prostitutes worked on average four days a week and had between two and three clients a night. Condoms were used in up to 80% of contacts. 795 clients of prostitutes were interviewed and found to be on average of low educational and occupational status. Half were non-Gambian and most were currently travelling or living away from home. PMID- 1738860 TI - Older widow mortality in rural Bangladesh. AB - Prospective data from rural Bangladesh are used to explore the adverse impact of widowhood on old age female mortality. The results indicate that widows aged 45 and above have significantly higher mortality than their currently married counterparts. Controlling for age and disability status, much of this excess mortality risk can be accounted for by patterns of living arrangements and household assets. An analysis of older widows suggests that the presence of adult male kin in the household (primarily sons), and to a lesser extent household headship (both of which may be interpreted as reflecting individual access to resources in this society) have a substantial impact on mortality risks for this group of women. PMID- 1738861 TI - Evaluation of a mobile branch surgery in a rural area. AB - Access to the family doctor at his or her surgery is a problem for many people living in rural Britain. The service provided by a caravan used as a general practice mobile branch surgery in a rural part of Norfolk was evaluated using a survey of residents and examination of practice records. In a village where the mobile surgery replaced a conventional branch surgery, consultation rates increased slightly during the first year of operation. In a village where the mobile surgery was a new facility, consultation rates increased substantially in the first year. Replies from residents indicated that although the limitations of the mobile surgery were recognised, the service reduced the problems of physical access in remote villages to the level of those in the village where the main surgery is situated. PMID- 1738862 TI - Forensic anthropology and the concept of race: if races don't exist, why are forensic anthropologists so good at identifying them? AB - Most anthropologists have abandoned the concept of race as a research tool and as a valid representation of human biological diversity. Yet, race identification continues to be one of the central foci of forensic anthropological casework and research. It is maintained in this paper that the successful assignment of race to a skeletal specimen is not a vindication of the race concept, but rather a prediction that an individual, while alive was assigned to a particular socially constructed 'racial' category. A specimen may display features that point to African ancestry. In this country that person is likely to have been labeled Black regardless of whether or not such a race actually exists in nature. PMID- 1738863 TI - Forensic archaeology as mortuary anthropology. AB - This paper argues that forensic anthropology is more than just physical anthropology, but should incorporate several subdisciplinary perspectives into a framework of mortuary anthropology. The advantage of this holistic approach is to provide context for the primary roles of physical anthropologists; identification of victims, and assessing manner of death. Mortuary anthropology provides information on processes of disposal and site formation, including the regularity, sequencing, and timing of events, which is complementary to the traditional roles of physical anthropologists. A call is made for more widespread application of this perspective. PMID- 1738864 TI - Racial identification in the context of prehistoric-historic biological continua: examples from South Asia. AB - The practice of 'racial palaeontology' disappeared 50 years ago with the fall of the biological race concept in systematics and population genetics. However, certain ethnic minorities claim close biological affinities with extinct (sometimes Pleistocene) populations. Forensic anthropologists may be involved in this issue through analyses of prehistoric and modern populations in circumstances where a biological continuum may exist. Skeletal evidence from South Asia is discussed. PMID- 1738865 TI - Forensic diagnosis of race--general race vs specific populations. AB - Commonly used methods of diagnosing racial affinity from the skull may give paradoxical results. This may be due to using single populations to represent large geographical areas, and to the use of measurements unduly subject to local variation. It is suggested that a more flexible approach, using appropriate local populations and selected measurements, would be entirely practical with the use of modern small computers. PMID- 1738866 TI - Physicians and the state in the U.S.A. and Israel. AB - The paper focuses on two patterns of policy-making: a professional pattern in which physicians dominate, and a political pattern in which state authorities take the lead. It looks into the causes of the emergence of each of these patterns and their consequences, in terms of the equity of the health services and their efficiency. The U.S.A. and Israel provide examples for the professional and political patterns of health policy making. The causes for the development of the political pattern in the U.S.A. are grounded in the social salience of medical care, in physicians' economic power, and in the individualistic political culture. The politicization of health services in Israel came about owing to the low placement of health on the social agenda, the proletarianization of physicians, and the hierarchical administrative culture. Analysis of the results indicates that Israel portrays more equity in health services. However, in terms of efficiency results are mixed. In both countries, changes are taking place in opposite directions: more politicization in the U.S.A.; less in Israel. PMID- 1738867 TI - Psychiatric diagnosis and racial bias: empirical and interpretative approaches. AB - Understanding of psychiatric illness among Britain's Black and ethnic minority population has shifted from an emphasis on cultural difference to one on racism within psychiatric theory and practice. In spite of this apparent turn, the explanations put forward remain within an empirical framework of methodological individualism, reflecting the background and training of British psychiatrists themselves. How racism may be actually demonstrated in individual clinical practice remains elusive. The standard hypotheses are examined here through a conventional clinical vignette study: this suggests medical education does not in itself now involve any specific racist psychiatric assumptions. Fuller understanding of the exercise of social power within this particular domain requires not only more complex interactive studies, preferably derived from a variety of clinical and social contexts, but a more developed interpretation of psychiatric practice and ideology within the social system. PMID- 1738868 TI - Ethnicity, morbidity and health service utilization in two Labrador communities. AB - This paper compares total outpatient health care utilization of residents of the Labrador community of Sheshatshit, a predominantly native Innu settlement, with those for the adjacent and predominantly caucasian community of Northwest River for 1986. In lieu of a community survey, these data provide an approximation of the morbidity patterns within the populations. Findings indicate that the native population experiences proportionately more infectious diseases (39.3% of all visits compared to 12.5% of all visits for the non-native community). While residents of the Innu community utilize health services primarily for curative care, residents of Northwest River sought services for both curative and preventive care. It is concluded that inequalities in material wellbeing may underlie the morbidity in Sheshatshit. While desirable in light of the WHO Ottawa Charter, any modification of the health services on account of these morbidity patterns will have only modest effect until policy-based initiatives to reduce material inequalities are implemented. PMID- 1738869 TI - Child health outcomes among Central American refugees and immigrants in Belize. AB - The purpose of this study was to investigate the effect of international migration, including refugee status, upon child health outcomes. Data were drawn from a survey conducted in 1989 in three settlements in Belize, Central America, that have a high proportion of refugees and economic immigrants living side-by side with the local population. In two of the settlements, the entire population of mothers with children under 6 was interviewed; in the third settlement a two thirds random sample was interviewed. Health history data were obtained for 255 children of 134 mothers, from whom sociodemographic data were also collected. The majority of children were born to Salvadoran or Guatemalan mothers, but native and naturalized Belizeans in the survey communities were included for comparison purposes. Migration, the exposure variable, was characterized by mother's residency/refugee legal status, nationality, and duration of time in country. Socioeconomic and proximate control variables were included as suggested by the Mosley-Chen framework. Despite normal birthweight averaging 3374 g, a large proportion of children are at the lowest percentiles of the weight-for-age curves (44% below the tenth percentile for the international reference population). A high incidence of diarrheal and respiratory illnesses (30% and 47% of children, respectively, having frequent episodes), and 50% of children with measles vaccination appropriate for age, indicate a population with high potential morbidity. Logistic regression was used to model the effects of migration on weight-for-age and frequency of diarrheal and respiratory tract episodes independent of socioeconomic and proximate factors, as suggested by the Mosley Chen framework.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1738870 TI - Pursuing health for all in Britain--an assessment. AB - In 1977 the World Health Organisation adopted the strategic goal "Health For All by the Year 2000". The Regional Office for Europe of the World Health Organisation has taken important steps toward the attainment of the goal, with the formulation in 1980 of a common health policy and the adoption by the Regional Committee in 1984 of 38 wide-ranging targets. The targets represent a common view of what could be Health For All in Europe and constitute a major challenge which the 33 member states in the European Region have set for themselves. Thus, the targets offer a different way or approach to the building of a local strategy. This paper reviews the extent to which Health For All and its associated targets constitute part of the planning process at district level. At the core of the paper is the results of a survey of health authorities and boards in the United Kingdom which sought details on the extent to which health planners and policy makers have embraced the concept of Health For All in applying it to a local setting. The findings of the survey are discussed within the context of whether or not Health For All should be a centrally driven or locally derived policy. And how the experience in Britain could be of value to others embarking on such a venture. PMID- 1738871 TI - Elasticity of demand for water in Khartoum, Sudan. AB - A survey of the quantities of water purchased from vendors in the squatter areas of Khartoum, Sudan, was used to assess the effect of the price charged for water and of household income on domestic water consumption. Households in two squatter communities--Meiyo and Karton Kassala--were studied by observation and by interview. In spite of the substantially higher charges, water consumption in Karton Kassala was as high as that in Meiyo. Households within these communities showed no tendency to use less water when paying a higher price for it, or when their income was below average. In other words, no price elasticity or income elasticity was detectable. This was all the more striking in view of the high proportion of income that was spent on water; 17% in Meiyo, and 56% in Karton Kassala. One consequence of this lack of elasticity is that the poorest households devote the greatest percentage of their income to the purchase of water, although the only major item in their household budget which can be sacrificed to make this possible is food. The high price of water in urban Sudan is probably a major cause of the malnutrition prevalent in the squatter areas. Another consequence is that a low-income household's consumer surplus for domestic water is very high, amounting to a substantial proportion of its total income. This has important consequences for the economic appraisal of urban water supply schemes. It also follows that wealthier households with private connections would be willing to pay at least as much for water as that currently paid by the poor. PMID- 1738872 TI - Preventive health behavior among black and white women in urban and rural areas. AB - The relationship of race to preventive health behavior among women is examined using data from the 1985 National Health Interview Survey. We find that black women are less likely to engage in primary prevention behaviors such as exercising, non-smoking and maintaining a favorable weight. However, black women are more likely to engage in secondary prevention behaviors such as receiving a Pap test or a breast exam. These findings are surprising as they indicate a change in secondary prevention behavior among black women. The racial differences in exercising, maintaining a favorable weight and receiving a Pap test or a breast exam cannot fully be explained by the differing levels of socio-economic status, measured by education and income. However, the higher percentage of smoking among black women is due to their lower levels of education. Urban/rural residence modifies the effect of race on smoking and receiving a Pap test. Black women in urban areas are most likely to be smokers. Almost no difference exists between white women in urban and rural areas concerning their likelihood of receiving a Pap test, we find that black women in urban areas are much more likely to be screened for cervical cancer than black women in rural areas. PMID- 1738873 TI - Eosinophilic meningitis beyond the Pacific Basin: the global dispersal of a peridomestic zoonosis caused by Angiostrongylus cantonensis, the nematode lungworm of rats. AB - The principal etiologic agent of human eosinophilic meningitis, Angiostrongylus cantonensis, was first detected in rats in Canton, China in 1933. The first human case was detected on Taiwan in 1944. Epidemic outbreaks were noted on Ponape (E. Caroline Is.) from 1944 to 1948. The disease may present as transient meningitis or a more severe disease involving the brain, spinal cord and nerve roots, with a characteristic eosinophilia of the peripheral blood and CSF. Since 1961 it has been known that human infections are usually acquired by purposeful or accidental ingestion of infective larvae in terrestrial mollusks, planaria and fresh-water crustacea. There is no effective specific treatment. The African land snail, Achatina fulica played an important role in the panpacific dispersal of the organism: it will be important in Africa in the future as well. Rats were, and will continue to be the principal agents of expansion of the parasite beyond the Indopacific area. During and just after WWII the parasite was introduced, and/or spread passively from South and Southeast Asia into the Western Pacific islands and eastward and southward through Micronesia, Melanesia, Australia and into Polynesia, sequestered in shipments of war material and facilitated by post-war commerce. In the 1950s numerous cases were identified for the first time on Sumatra, the Philippines, Taiwan, Saipan, New Caledonia, and as far east as Rarotonga and Tahiti. Then cases were detected in Vietnam, Thailand, Cambodia, Java, Sarawak, the New Hebrides, Guam and Hawaii during the 1960s. Subsequently in the Pacific Basin the disease has appeared on Okinawa, other Ryukyu islands, Honshu, Kyushu, New Britain, American Samoa and Western Samoa, Australia, Hong Kong, Bombay, India, Fiji and most recently in mainland China. The parasite in rats now occurs throughout the Indopacific Basin and littoral. Beyond the Indopacific region, the worm has been found in rodents in Madagascar (ca 1963), Cuba (1973), Egypt (1977), Puerto Rico (1984), New Orleans, Louisiana (1985) and Port Harcourt, Nigeria (1989). Human infections have now been detected in Cuba (1973), Reunion Island (1974) and Cote d'Ivoire (1979) and should be anticipated wherever infected rats of mollusks have been introduced. Caged primates became infected in zoos in Hong Kong (1978) and New Orleans and Nassau, Bahamas (1987). The use of mollusks and crustacea as famine foods, favored delicacies and medicines has resulted in numerous outbreaks and isolated infections. Economic and political instability, illicit trade, unsanitary peridomestic conditions and lack of health education promote the local occurrence and insidious global expansion of parasitic eosinophilic meningitis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1738874 TI - Why clinical trials fail: the hidden assumptions of clinical trials. PMID- 1738875 TI - First-order prevention and second-order treatment: health care in the developed world is too long on the latter. PMID- 1738876 TI - Psychologic sequelae of chronic toxic waste exposure. AB - Exposure to toxic industrial substances has been a topic of increasing concern to environmentalists, government agencies, industrial engineers, and medical specialists. Our study focuses on the psychologic symptom responses of a community to perceived long-term exposure to toxic waste products. We compared their symptom clusters, as shown by their responses to questions on the Hopkins Symptom Checklist-90 Item (SCL-90) and the Social Adjustment Scale (SAS), with symptom levels of normal and depressed subjects. Issues of media coverage, litigation, and potential for compensation complicate the psychiatric epidemiology of the subject. PMID- 1738877 TI - Drug therapy in the elderly. AB - The segment of the population older than 65 accounts for about 25% of the total drug expenditures in developed countries. This figure is predicted to reach 40% by the year 2030. Drug therapy in the elderly can be complicated by many factors. The pharmacokinetic processes of absorption, distribution, metabolism, and elimination are altered by the physiologic changes of aging involving body composition and organ function. While the extent of drug absorption is not affected by age, few drugs have delayed rates of absorption after oral administration. Changes in body composition, protein binding, and blood flow do affect the concentrations of free unbound drug, the volume of distribution, and elimination half-life of a number of drugs. The primary goal of drug therapy in the elderly is to improve the quality of life. When medical therapy is required, the physician must be aware of the potential effect of age and disease on pharmacokinetics and pharmacodynamics and of the possible ramifications for adverse drug reactions or interactions. By increasing our knowledge of the action and effects of drugs in the elderly, and by enhancing communication and understanding between physician and patient, we can significantly improve the overall quality of care for the elderly patient. PMID- 1738878 TI - Antineutrophil cytoplasmic antibodies: clinical characteristics of 10 patients with the perinuclear pattern of immunofluorescence on ANCA testing. AB - Antineutrophil cytoplasmic antibodies (ANCA) have recently been described in association with necrotizing glomerulonephritis, systemic vasculitis, and other autoimmune-mediated connective tissue diseases, including systemic lupus erythematosus (SLE) and polychondritis. At least two distinct classes of ANCA have been described, differentiated by characteristic immunofluorescence patterns using neutrophils as substrate for indirect immunofluorescence assay (IFA). A focal, centrally accentuated, finely granular cytoplasmic staining pattern (c ANCA) is both sensitive and specific for Wegener's granulomatosis (WG) and is thus a useful clinical adjunct in the diagnosis and monitoring of disease activity in WG. The second class of ANCA, defined by a perinuclear immunofluorescent staining pattern (p-ANCA) on standardized IFA, has not been studied as extensively. It appears to occur in a variety of connective tissue diseases, most often necrotizing glomerulonephritis other than WG, systemic vasculitis with renal involvement, and SLE. In screening more than 2000 serum samples received in our rheumatology laboratory for ANA testing, we found p-ANCA in 10 patients. All 10 had evidence of systemic autoimmune disease, though with wide variation in extent and severity of disease. All 10 had other autoantibodies, most frequently ANA (60%). Our studies suggest that p-ANCA define a heterogeneous patient population with a spectrum of autoimmune disease, most frequently necrotizing glomerulonephritis and systemic vasculitis. Future studies will establish the role of p-ANCA in clinical medicine and broaden our understanding of the origin and possible pathogenesis of ANCA and autoantibodies in general. PMID- 1738879 TI - Transplacentally transmitted autoimmune disorders of the fetus and newborn: pathogenic considerations. AB - Autoimmune diseases affect a significant number of women in their childbearing years. This group of disorders constitutes a heterogeneous spectrum with a common basis involving the presence of autoantibodies often of the IgG type. Transplacental transfer of autoantibodies is not uncommon, and autoantibodies can be readily demonstrated in newborn serum. Only a small proportion of infants with circulating autoantibodies exhibit clinical symptoms. The transient neonatal manifestations of maternal autoimmune disease disappear over a time course consistent with the catabolism of IgG, providing no permanent damage occurs. Thus the pathogenic role of transferred autoantibodies seems well established. However, maternal-autoantibody-mediated tissue damage appears to depend on factors other than the mere passage of the antibody to the fetal compartment. This review details putative factors that are likely to modulate the clinical expression of the fetal antigen-autoantibody reaction in offspring of mothers with autoimmune disorders. The importance of amount, type, and specificity of autoantibodies is described. The possible significance of fetal and maternal immunogenetics is briefly discussed, as well as the limited knowledge currently available on the fetal development of fetal antigenic sites at target organs. These and other as yet unidentified factors may help explain the rarity of clinical manifestations in infants exposed to potentially pathogenic maternal autoantibodies. PMID- 1738880 TI - Topical pharmacotherapy for allergic rhinitis: new agents. AB - The advantages of topical (as opposed to systemic) therapy for allergic rhinitis include the avoidance of undesirable systemic effects and the concentration of therapeutic effect on the target organ. Successful topical therapy requires establishment of a proper diagnosis, followed by effective delivery of the medication to the nasal mucosa. In addition to currently available preparations such as cromolyn sodium and various corticosteroids, several other topical nasal preparations for the treatment of allergic rhinitis are under investigation. These include antihistamines (eg, levocabastine), anti-inflammatory/mast cell stabilizing drugs (eg, nedocromil), new corticosteroids (eg, triamcinolone, budesonide, fluocortin, fluticasone), anticholinergics (eg, ipratropium), and miscellaneous agents (eg, HEPP [IgE pentapeptide]). PMID- 1738881 TI - Cone biopsy in premenopausal women: why was outpatient management abandoned? AB - In a 2-year retrospective study, I reviewed the records of 180 premenopausal patients who had had cone biopsy. The purpose of this study was to determine the indications for the procedure in the view of the practicing clinician and to determine whether these young women might have received better treatment as outpatients. In this series, positive findings on endocervical curettage (ECC) in patients with otherwise satisfactory results of colposcopy was by far the leading reason for cone biopsy, and positive findings on ECC did not correlate with occult disease in the canal when the cone specimen was examined. Also, a significant number of women had cone biopsy solely for severe dysplasia, though the literature clearly shows the effectiveness of outpatient management in these cases (eg, using proper cryotherapeutic methods). If ECC is done routinely despite satisfactory results of colposcopic examination and unexpectedly positive results are obtained, I recommend repeat colposcopy with aggressive use of an endocervical speculum and a careful, adequate ECC before abandoning outpatient management. Proper histologic interpretation of ECC in light of all clinical data is essential to avoid unnecessary morbidity. PMID- 1738882 TI - Automatic implantable cardioverter-defibrillator: early experience at Wilford Hall USAF Medical Center. AB - Fifteen patients with malignant ventricular arrhythmias were treated with the automatic implantable cardioverter-defibrillator (AICD) over a 22-month period. The cause of the arrhythmia was coronary artery disease in 13 of the patients (87%), sarcoid cardiomyopathy in one (7%), and a primary electrical abnormality in one (7%). The mean ejection fraction was 29%, with a range of 15% to 70%. Fourteen of the patients had inducible ventricular tachycardia using program stimulation. Defibrillating and rate-sensing leads were inserted through a lateral thoracotomy in 13 patients and through a median sternotomy in two patients in conjunction with other cardiac procedures. The generators were positioned in a subcutaneous pocket beneath the left costal cartilage. There was one early and one late death, both due to congestive heart failure. Neither was related to a ventricular tachyarrhythmia, and in each patient the AICD was functioning properly at the time of death. The mean follow-up period was 11.5 months, with five patients receiving a total of 17 shocks. We conclude that the AICD is a highly effective, low-risk treatment for malignant ventricular tachyarrhythmias. PMID- 1738883 TI - Lesions of the nasal radix in pediatric patients: diagnosis and management. AB - Lesions involving the nasal radix are not extremely uncommon in the pediatric population. Such lesions may represent inflammatory or infectious processes, neoplasia, traumatic sequelae, or developmental anomalies, but faulty embryogenesis is considered the most common cause. During my surgical experience, I have encountered nasal dermoids, nasal gliomas, and nasal encephaloceles resulting in lesions at the root of the nose. Each of these has unique features that will affect therapy. PMID- 1738884 TI - Theoretic orientations and folk medicine research in the Appalachian South. PMID- 1738885 TI - Antineutrophil cytoplasmic antibody associated with pulmonary hemorrhage: Wegener's granulomatosis? AB - Antineutrophil cytoplasmic antibodies have been described mainly in patients with Wegener's granulomatosis. It has proven useful for both diagnosis and follow-up in these patients. We have described a patient with diffuse pulmonary hemorrhage in whom the suspicion of Wegener's granulomatosis was raised by the identification of antineutrophil cytoplasmic antibodies. PMID- 1738886 TI - Miliary tuberculosis: unusual cause of abdominal pain in pregnancy. AB - We have described a case of miliary tuberculosis, with symptoms primarily due to hepatic involvement during pregnancy. Liver biopsy showed granulomatous hepatitis, and subsequent cultures of sputum, urine, and gastric aspirate were positive for Mycobacterium tuberculosis. Although this patient was seronegative for HIV, an increased incidence of extrapulmonary and disseminated tuberculous infection has recently been noted in patients with HIV infection. Given the increasing incidence of HIV in the general population, we may therefore anticipate a corresponding rise in the incidence of extrapulmonary tuberculosis. Since an increasing number of gravidas will be immunocompromised by HIV infection, renewal of knowledge regarding diagnosis of miliary tuberculosis in pregnancy is valuable. PMID- 1738887 TI - Lyme arthritis with subarticular cyst formation in metacarpal and metatarsal bones. AB - A young woman was treated for seronegative rheumatoid arthritis for more than 9 years, without clinical improvement, before the diagnosis of chronic Lyme arthritis of the metacarpal and metatarsal phalangeal joints was made. Roentgenograms showed subarticular cyst formation in the metacarpal and metatarsal bones. The patient's response to treatment with a 2-week course of ceftriaxone was dramatic. PMID- 1738888 TI - Listeria monocytogenes causing endovascular infection. AB - Listeria monocytogenes is an uncommon cause of mycotic aneurysms, endocarditis, and other endovascular infections. When they occur, these infections usually involve patients with relatively normal host defenses, but with abnormal vascular intima or cardiac valves. We have reported a Listeria monocytogenes infection at the site of a posttraumatic aortic aneurysm. PMID- 1738889 TI - Adrenal insufficiency and stage D carcinoma of the prostate. AB - A patient with stage D prostatic cancer but in reasonably good general health was discovered to have adrenal failure and tumor destruction of the adrenal glands. Because prostatic cancer is common and compatible with prolonged survival, we surveyed other patients with stage D prostatic cancer. On initial screening with the cosyntropin test, we found that 5 of 14 patients failed to respond with an increase in serum cortisol of 10 micrograms/dL, suggesting an adrenal failure incidence of 36%. Retesting, however, indicated that probably all of these were false-positive results. PMID- 1738890 TI - Azathioprine: effective steroid-sparing therapy for generalized lichen planus. PMID- 1738891 TI - Infantile gastrointestinal hemangioma as a cause of chronic anemia. AB - Gastrointestinal hemangiomas, though rare, can be an important source of GI bleeding in infants. In the past, diagnosis has been hampered by a lack of reliable methods. With the recent advent of selective mesenteric angiography, the suspected diagnosis can be readily confirmed. Surgical resection remains the definitive therapy; steroid therapy has produced conflicting results. PMID- 1738892 TI - Cushing's syndrome with cranial and pulmonary lesions: necessity for tissue diagnosis. AB - This report describes two cases of Cushing's syndrome associated with radiologic abnormalities in the lung and brain. In both cases, the pathologic diagnosis of the intracranial lesion was unsuspected and prompted changes in management. These cases illustrate that the etiology of pulmonary and central nervous system mass lesions in patients with Cushing's syndrome may not be predicted on clinical grounds or by conventional radiologic methods. A tissue diagnosis is essential as a guide to appropriate management, and biopsies of such lesions are indicated. PMID- 1738893 TI - Cholesterol microembolization and stable renal function with continued anticoagulation. AB - Cholesterol microembolization as a sequela of oral anticoagulant therapy has been reported to cause infarction of virtually any organ, often resulting in death. Until recently, discontinuance of anticoagulant therapy has been recommended, as this cessation has been shown to slow or halt further tissue infarction. I have described a patient with a prosthetic heart valve in whom the purple toes syndrome developed. Stable renal function followed the initiation of high-dose subcutaneous heparin therapy. PMID- 1738894 TI - EDTA-induced pseudothrombocytopenia. AB - A 45-year-old man was admitted to the hospital because of unstable angina pectoris. During the wait for coronary artery bypass surgery, the platelet count gradually decreased from 154,000 to 20,000/mm3, without hemorrhagic manifestations. Medications were discontinued and surgery was postponed. Direct blood smear revealed a normal number of platelets, establishing the diagnosis of pseudothrombocytopenia. The mechanism of the development of pseudothrombocytopenia is not clear. PMID- 1738895 TI - Pancytopenia caused by unsuspected pernicious anemia complicating sickle cell beta-thalassemia. AB - We have described a a 23-year-old black woman with sickle cell beta-thalassemia who had a urinary tract infection and who was incidentally found to be pancytopenic. Although her anemia was categorized as "normocytic, normochromic" by an electronic particle counter, evaluation of the pancytopenia confirmed unsuspected pernicious anemia. Greater vigilance and a higher index of suspicion are crucial for early diagnosis of pernicious anemia in patients with other known hemoglobinopathies. PMID- 1738896 TI - Transvaginal intra-abdominal impalement injury. AB - Impalement injuries due to sexual activity are highly unusual and variable. We have described a case of transvaginal impalement injury of the rectum, bladder, omentum, and mesentery manifested by vaginal bleeding. The patient could not recount how she had been injured. Management of such an injury requires extensive initial evaluation and a multidisciplinary approach to therapy. PMID- 1738897 TI - Drug interactions with oral contraceptives. PMID- 1738898 TI - The future of CME. PMID- 1738899 TI - Prolonged recrudescence of Plasmodium falciparum. PMID- 1738900 TI - Medicine--business or profession? PMID- 1738902 TI - Angiotensin-converting enzyme inhibitor therapy. PMID- 1738901 TI - Vitamin A, childhood mortality, foresight and epidemiology. PMID- 1738903 TI - Telling patients the truth. PMID- 1738904 TI - Listeria monocytogenes meningitis at King Edward VIII Hospital, Durban. A 10-year experience, 1981-1990. AB - Nine cases, 3 adults and 6 children, with Listeria monocytogenes meningitis were seen over a 10-year period at King Edward VIII Hospital, Durban. These cases accounted for 0.8% (3/374) and 0.6% (6/1,210) of all culture-positive cases of acute bacterial meningitis in adults and children, respectively, and represented 2.9% (4/136) of all culture-positive cases in the neonatal age group and 5.7% (3/53) of culture-positive cases in adults 50 years and older. The patients had positive blood and cerebrospinal fluid (CSF) cultures. All isolates were sensitive to ampicillin, chloramphenicol, sulphamethoxazole-trimethoprim combination and gentamicin. One isolate in an 11-month-old child was resistant to penicillin and 2 isolates in the adult patients displayed intermediate sensitivity to this antibiotic. The adults were over 50 years of age and presented with an abrupt onset of a pyrexial illness, meningitis and focal neurological signs; only 1 survived. Only 1 8-week-old infant of the paediatric cases survived. A polymorphonuclear leucocytosis, low serum glucose and elevated protein values were common findings in the CSF and the features in some patients mimicked tuberculous or viral meningitis. The fulminant course of the disease and the fact that penicillin and not ampicillin is the first-line antibiotic makes it essential to consider listeriosis as a possible diagnosis, particularly in the very ill patient. PMID- 1738905 TI - Information yield from routine pre-operative chest radiography and electrocardiography. AB - Studies in First-World settings suggest that routine pre-operative investigations are of minimal usefulness. A retrospective study of 797 case records determined the yield of significant information from routine chest radiography and ECG in a provincial general hospital serving a broad socio-economic sector. The results were in agreement with those of other studies, viz. that routine investigation may be worthwhile only in older patients. Routine chest radiographs showed an overall positive yield of 6%; 17% in those over 60 years but only 2% in those under 60 years. Routine ECGs showed a positive yield of 7% overall; 7.4% in those older than 40 years and 4.5% in those under 40 years. Investigations indicated by history or physical examination had a significantly greater yield: 34% for chest radiography and 31% for ECGs. Positive results of indicated investigations were more evenly spread across the age groups. The pre-eminence of clinical skills in determining which patients require special investigations is reaffirmed. PMID- 1738906 TI - Occupational diseases in South African mines--a neglected epidemic? AB - A major difficulty in assessing incidence and prevalence of occupational diseases among the workforce employed on South African mines is the lack of epidemiological data. Published and unpublished data were collated and analysed for the period 1915-1988 in order to provide insights into occupational disease trends. Using proxies for incidence rates, it was demonstrated that the rates of silicosis and tuberculosis were likely to be high. In the case of silicosis among black miners, disease was contracted in a relatively short period on average. The stabilisation of the black workforce on the mines, which started in 1975 and continues, is an important factor likely to lead to an increase in occupational disease rates. Recommendations for improved data reporting and research are made, in particular the need to identify occupational groups at high risk and the calculation of prevalences. PMID- 1738907 TI - Infant and child mortality in the Elim District, northern Transvaal, 1976-1986, and a comparison of trends. AB - Childhood mortality rates among rural blacks in South Africa are currently not based on a reliable registration system. National childhood mortality statistics rely on mortality extrapolations and population estimates. This study attempts to provide further information on infant and child mortality among rural blacks in the northern Transvaal, using a direct method. Currently available obstetric histories from hospital and clinic records of the Elim Hospital Health Ward were reviewed, covering the years 1976-1988 and approximately 28,000 pregnancies. The mean infant mortality rate was 88/1,000 live births, and did not change significantly over 10 years, in contrast to other populations in South Africa with documented decreases. Components of the infant mortality rate were also calculated. There was a 1 in 10 risk of death among children less than 5 years of age over this period, although the risk had declined slightly over 10 years. Mortality among boys was higher than that among girls in all age groups studied. Conclusions include that small but measurable changes have occurred in rural South African black childhood mortality rates, although there has been no discernible change in infant mortality, and that a simple direct method can illustrate levels as well as trends in mortality. This has implications for health policy. PMID- 1738908 TI - Vaccination status of children aged 12-23 months in the Northern Transvaal Health Region. AB - A vaccination coverage survey was done between October and December 1989 in the Northern Transvaal Health Region, as the first phase in the region's contribution to the National Measles Strategy. The aim of the study was to evaluate the vaccination status of children in this region aged 12-23 months. The study population was divided into four strata, a black and a white urban stratum and two rural black strata, one in the north-western and the other in the south eastern part of the region (self-governing and independent territories excluded). The Expanded Programme on Immunisation (EPI)-recommended cluster sampling technique was used in each stratum. The data were collected by nursing staff working in the area, after they had received special training. A questionnaire was used to obtain data from randomly selected households. The following conclusions can be made from the results: (i) in all strata percentages of fully vaccinated children were well below the EPI-recommended target of 60-70% to be reached by the developing countries by 1990; (ii) a danger of measles outbreaks exists in most communities, because the levels of measles vaccination were less than 70% in three out of the four strata; (iii) the children with the highest risk of developing measles complications were not being vaccinated early enough; and (iv) the very high drop-out rates for subsequent vaccinations in the rural areas warrant urgent attention. PMID- 1738909 TI - Protein energy malnutrition and its recognition in outpatient departments in Venda hospitals. AB - Between April and June 1988 the number of children under 5 years old attending outpatient departments of Venda hospitals who had protein energy malnutrition (PEM) was determined, the proportions at 3 Venda hospitals were compared, and what percentage of these children was detected by attendant health workers was determined. Approximately 6% had severe PEM; this finding was consistent for all 3 hospitals. The rates for mild PEM were 22% for Tshilidzini and Donald Fraser Hospitals and 33% for Siloam Hospital. This statistically significant difference has not been explained. Health workers failed to recognise about 25% of children with severe PEM and 50% of children with mild PEM. It is suggested that certain interventions and activities are essential if PEM is to be adequately managed: these are efficient monitoring; pre-employment and in-service education for health workers; a breast-feeding and weaning survey; and an investigation of the variation of malnutrition among Venda hospitals. PMID- 1738910 TI - Child health in farm workers' communities. AB - Black women who had borne one or more children in the 5 years preceding the study and who were resident on white-owned farms were sampled in a multistage cluster procedure from the population of two magisterial districts of the southern Transvaal, Ventersdorp and Balfour. The purpose of this study was to determine mothers' knowledge and behaviour regarding the health of their children, to correlate this with personal and social characteristics of the mothers, and to document aspects of their physical environment. Only 50% of mothers had completed 4 or more years of formal education. One in three had experienced the death of at least 1 of her children. Water and sanitation facilities were inadequate for most. Little was known about oral rehydration solution preparation or about growth monitoring. Most children were breast-fed. Between 50% and 63% of the children had vaccinations appropriate for their ages, depending on whether evidence from clinic cards or from mothers' memories was taken as valid. The single most important determinant of the appropriate knowledge and behaviour of mothers was education. Basic living and social conditions of farm workers require improvement and the health services must be re-orientated to deliver comprehensive primary care. PMID- 1738911 TI - Changes in penile skin blood flow following intracavernosal injection of papaverine. AB - Marked changes in penile skin blood flow following intracavernosal injection of papaverine were observed in 14 subjects. Increased flow was more pronounced in those patients who failed to achieve erection or had poor erection than in those who responded with adequate erection. This observation may explain in part why papaverine fails in subjects responding to prostaglandin E1. It raises the suspicion of a corporal cutaneous shunt, which may influence the choice between the use of an external vacuum device and venous surgery in certain cases of venogenic impotence. PMID- 1738912 TI - Weskoppies Hospital, founded 1892--the early years. AB - The Krankzinnigengesticht te Pretoria (Pretoria Lunatic Asylum) was established in 1892 as the first and only psychiatric institution in the Zuid-Afrikaansche Republiek (now the Transvaal). The asylum was later renamed Weskoppies Hospital. The first 10 years of the hospital's history, including the turbulent years of the Anglo-Boer War, are described. Attention is given to the institution's management, the diagnosis and treatment of patients and the effectiveness of such treatment. The hospital's medical director followed an enlightened approach to caring for the mentally ill, in line with the policies of psychiatric hospitals in contemporary Europe. However, his ideals of no restraint and minimal confinement of patients could not be maintained during the war years owing to insufficient accommodation and a lack of suitably trained attendants. It is concluded that the humane care of the institutionalised psychiatric patient was (and is) not guaranteed by enlightened policies, but depends on sufficient resources to put such policies into practice. PMID- 1738913 TI - A simple urinary screening test to differentiate between upper and lower urinary tract haematuria. PMID- 1738914 TI - Causes of perinatal death. PMID- 1738915 TI - Causes of perinatal death. PMID- 1738916 TI - Immunological status of children with Kawasaki syndrome. PMID- 1738917 TI - Inhibition of host-versus-graft and graft-versus-host responses after small bowel transplantation in rats by rapamycin. AB - The effect of rapamycin (RAPA) on both host-versus-graft (HVG) and graft-versus host (GVH) immune responses was examined in small bowel transplant models using strongly histoincompatible donor-recipient combinations. Normal Wistar Furth (WFu; RT-1u) recipients rejected Buffalo (BUF; RT-1b) small bowel allografts within a mean survival time (MST) of 10.5 +/- 0.5 days. Administration of RAPA (0.8 mg/kg) by continuous intravenous infusion for 14 days via an osmotic pump prolonged graft survival to 25.0 +/- 4.6 days (P = 0.01). In a second strain combination, the 12.5 +/- 2.2 day survival of Brown Norway (BN; RT-1n) small bowel allografts in Lewis (RT-1l) recipients was prolonged to 21.6 +/- 2.0 and 28.5 +/- 2.8 days by 14 days of i.v. RAPA at doses of 0.8 and 1.6 mg/kg, respectively. In this model RAPA is five times more effective than cyclosporine, which at 4.0 mg/kg prolongs BN small bowel allografts in Lewis recipients to 21.6 +/- 6.3. To isolate HVG and GVH immune responses, (BN x Lewis)F1 hybrid rats served as the graft donor or host, respectively. In the HVG model, (BN x Lewis)F1 small bowel allografts, which were rejected by normal Lewis recipients at 12.2 +/ 3.6 days, were prolonged to 40.8 +/- 5.8 days (P = 0.001) by RAPA (0.8 mg/kg x 14 days). In the GVH model, the ability of Lewis small bowel allografts to produce severe GVH disease in untreated (BN x Lewis)F1 recipients at 12.3 +/- 2.8 days was delayed to 21.3 +/- 5.2 days by 0.8 mg/kg RAPA (P = 0.025). Thus, RAPA protects small bowel allografts more effectively against HVG than GVH immune responses. PMID- 1738918 TI - Intestinal function following allogeneic small intestinal transplantation in the rat. AB - This study tests the hypothesis that small bowel transplantation alters the function of the intestine. The function of the small intestine was investigated after syngeneic (BN----BN or Lew----Lew) and fully allogeneic (BN----Lew) orthotopic total small intestinal transplantation (SIT) using a two-stage model. All animals were treated with cyclosporine A throughout the 60-day study period. Syngeneic transplantation reduced weight gain in the (BN----BN) rats, but not in the (Lew----Lew) animals. Allogeneic transplantation caused a reduction in weight gain for the first 30 days posttransplantation, which may have been associated with graft-versus-host disease. Thereafter, the rate of growth of allogeneic SIT animals was normal. Dietary fat absorption was reduced in all groups of transplanted animals. Intestinal permeability to mannitol and polyethylene glycol 400 (PEG-400) was increased by syngeneic transplantation in all groups, with further permeability increases to mannitol, lactulose, PEG-400, and 51Cr-EDTA after allogeneic SIT. The glucose-stimulated intestinal short circuit current was reduced by both syngeneic and allogeneic SIT, but the maximal active transport rate for glucose uptake was increased, as was the passive uptake of fatty acids. These functional alterations were not associated with changes in intestinal morphology or evidence of rejection. These findings demonstrate that: (1) SIT results in significant changes in the transport characteristics of the bowel, but these have a minimal impact on the well-being of the animal overall; (2) SIT induces an increase in intestinal permeability to mannitol and PEG-400, with a further increase in permeability to all markers following allogeneic SIT; (3) following SIT, and the immune events associated with allogeneic SIT, significant adaptation of the transplanted intestine occurs. We suggest that denervation of the small intestine after SIT is the underlying cause of the changes observed. PMID- 1738919 TI - Effects of cotransplanted fetal liver on fetal pancreas isografts. AB - Ricordi et al. described a hepatotrophic effect mediated by pancreatic islets on cotransplanted hepatocytes. We found a reciprocal salutary effect of fetal liver (FL) on fetal pancreas (FP) in the intramural small bowel (ISB) site. To further investigate this intriguing finding, composite FP/FL isografts were transplanted to the conventional renal subcapsular (RSC) site and the accessible but historically inhospitable intramuscular site in streptozotocin-diabetic Lewis rats. A comparison of recipients of FP/FL and FP alone found the proportion rendered normoglycemic was site dependent. All recipients of either composite FP/FL grafts or FP alone transplanted in the ISB site became normoglycemic. The proportion of normoglycemic recipients was lower in the RSC site (71% FP and 40% FP/FL) and the i.m. site (14% FP and 67% FP/FL). Importantly, regardless of site, normoglycemia was established with an accelerated time course in recipients of FP/FL versus FP alone (24 +/- 8 vs. 67 +/- 43 days; P = 0.001). Normal (or more rapid) glucose clearance after challenge was achieved in all normoglycemic recipients except those transplanted in the RSC site. On histological examination of excised FP/FL grafts, hepatocytes were present in association with islets. Cyclosporine-induced islet toxicity could not be overcome in 6 recipients of FP alone, but 6 of 8 recipients of FP/FL became normoglycemic (P less than 0.01). To assess the effect of FP on hepatocytes, allografts (Wistar donors) of FP or FP/FL were cotransplanted in the ISB of enzyme-deficient jaundiced Gunn rats. Immunosuppression consisted of rapamycin (0.8 mg/kg/day) infused intravenously for 4 weeks. In the FP/FL group (n = 4), the mean serum bilirubin level decreased from 8.6 to 4.9 mg/dl at 6 weeks after transplantation. This was a significant difference as compared with the increased mean serum bilirubin from 6.9 to 7.8 mg/dl (P less than 0.05; paired Student's t test) in recipients of FL alone (n = 4). In conclusion, we found a mutual paracrine effect on islets and hepatocytes transplanted as a composite FP/FL graft. FL hastened the establishment of normoglycemia following transplantation of FP in diabetic rats, and FP enhanced FL transplant function in Gunn rats. PMID- 1738920 TI - Long-term survival of donor-specific pancreatic islet xenografts in fully xenogeneic chimeras (WF rat----B10 mouse). AB - We recently reported that reconstitution of lethally irradiated B10 mouse recipients with 40 x 10(6) untreated WF rat bone marrow cells resulted in stable fully xenogeneic chimerism (WF rat----B10 mouse). In these animals, the tolerance induced for skin xenografts was highly MHC specific in that donor-specific WF rat skin grafts were significantly prolonged while MHC-disparate third-party xenografts were rapidly rejected (median survival time [MST] = 9 days). We have now examined whether islet cell xenografts placed under the renal capsule of chimeras rendered diabetic with streptozotocin would be accepted and remain functional to maintain euglycemia. Animals were prepared, typed for chimerism at 6 weeks, and diabetes induced with streptozotocin. Donor-specific WF (Rt1Au) islet cell xenografts were significantly prolonged (MST greater than 180 days) in WF----B10 chimeras, while MHC-disparate third-party F344 rat (Rt1A1) grafts were rejected with a time course similar to unmanipulated B10 mice (MST = 8 days). The transplanted donor-specific islet cells were functional to maintain euglycemia, since removal of the grafts at from 100 to 180 days in selected individual chimeras uniformly resulted in return of the diabetic state. These data suggest that donor-specific islet cell xenografts are accepted and remain functional in mice rendered tolerant to rat xenoantigens following bone marrow transplantation. PMID- 1738921 TI - Prolongation of cardiac allograft survival in rats by anti-TNF and cyclosporine combination therapy. AB - Cyclosporine is well known to have many adverse side effects. However, while decreasing the dosage of CsA can reduce its toxicity, this also lowers its immunosuppressive effectiveness. Additionally, anti-tumor necrosis factor has been demonstrated to have immunosuppressive activity and been shown to prolong cardiac allograft survival. This current study therefore investigated the efficacy of a combined therapy of anti-TNF with low-dose CsA in a rat heterotopic cardiac transplant model utilizing Brown-Norway donors and Lewis recipients. Control transplant recipients received no immunotherapy. Experimental animals received single-dose anti-TNF intraperitoneally on posttransplant days 0, 3, or 5 and/or low-dose CsA (1.5 mg/kg/day) intramuscularly from days 0 to 14 after transplantation. Rejection was determined by the lack of contractions in the transplanted heart. No animal received any other form of immunosuppression. Graft survival was significantly prolonged with combination CsA and anti-TNF therapy, suggesting a synergistic effect against acute cardiac allograft rejection, possibly from CsA and anti-TNF interacting at different levels of the recipient immune response. This form of combination therapy may hold promise for future immunosuppressive techniques. PMID- 1738922 TI - Limitations of heart preservation by cold storage. AB - Clinical heart preservation is currently limited to only 4-6 hr, while the kidney, liver, and pancreas can tolerate 24-48 hr of cold ischemia. A fundamental difference between these organs is that the heart is contractile, containing large quantities of actin and myosin, and is susceptible to contracture-induced injury caused by energy deprivation. We have quantified and correlated the onset of contracture with levels of ATP and glycogen during cold storage in rabbit hearts flushed with UW solution, with and without 1 mM calcium (Ca), or 3 mM iodoacetate (IAA). A fluid-filled left ventricular balloon was used to generate pressure-volume curves (compliance) at 1, 6, 12, 18, and 24 hr of cold storage. Onset of contracture occurred in UW stored hearts at 18 hr, contracture in hearts exposed to Ca occurred between 6 and 12 hr. Compliance was significantly less in hearts exposed to Ca at 12, 18, and 24 hr (P less than .01) than in hearts without Ca. ATP levels were well maintained for up to 18 hr in the hearts preserved in UW solution (78%), but fell more rapidly in the presence of Ca at 12 hr (P less than .005), 18 hr (P less than .005), and 24 hr (P less than .05). In comparison, the ATP supply of the liver and kidney was exhausted by only 4 hr of cold storage. Onset of myocardial contracture correlated with a decrease in ATP to less than 80% of control, and contracture accelerated ATP decline 3-6-fold. IAA caused nearly complete myocardial contracture and ATP depletion within 2 hr. Isolated heart function was 77% and 73% at 6 and 12 hr of storage, but fell to 54% and 42% at 18 and 24 hr, respectively, coinciding with development of contracture. We conclude that ischemic contracture in this model is a major cause of myocardial damage during cold storage, and is accelerated by the presence of Ca. Other organs can be successfully stored despite exhaustion of ATP reserves. Thus successful cold-storage of the heart is highly ATP-dependent. Since cold storage inevitably leads to ATP depletion, extension of myocardial ischemic tolerance will depend on either reversible inhibition of ATP hydrolysis during storage, reversible uncoupling of contracture development from ATP depletion, or maintaining ATP production by continuous hypothermic perfusion. PMID- 1738923 TI - Beneficial effects of cyclosporine on postischemic liver injury in rats. AB - The discovery of cyclosporine has had a significant impact on preventing the rejection of transplanted organs in humans. In this study, we present another positive aspect of cyclosporine. Rats were pretreated with cyclosporine (10 mg/kg, i.v.), or untreated. After 2-hr ischemia or 1 hr of reperfusion following 2-hr ischemia, livers were isolated and liver adenine nucleotide concentrations were determined. Liver mitochondria were prepared and their function was estimated polarographically. Leakage of AST, ALT, LDH, and adenine nucleotides into the hepatic vein just after reperfusion was also measured. Cyclosporine treatment did not affect ischemia-induced mitochondrial dysfunction, nor did it prevent the associated decrease in adenosine triphosphate concentration. However, treatment with cyclosporine accelerated the recovery of mitochondrial function and of tissue adenosine triphosphate concentrations. Cyclosporine treatment also mitigated leakage of AST, ALT, LDH, and adenine nucleotides after reperfusion. These results indicate that cyclosporine shows a potent protective effect on ischemia-reperfusion-related liver injury. PMID- 1738924 TI - Duodenal mucosal pH as a reperfusion indicator in pancreatic-duodenal transplantation in the pig. AB - We have studied differences in reperfusion between the pancreas and the duodenum after 6 hr of cold storage in a porcine whole-organ pancreaticoduodenal allograft transplantation model. Two different flush-out and storage solutions, Perfadex and EuroCollins, were compared. Graft duodenal mucosal pH (pHi) was measured as an indicator of duodenal mucosal reperfusion. Pancreatic reperfusion was estimated indirectly using a ratio between the release of immunoreactive cationic trypsin (irCT) to serum 10 and 60 min following reperfusion. Twelve pigs (Perfadex n = 6, EuroCollins n = 6) were transplanted and all showed preserved endocrine and exocrine function postoperatively. Our data support the concept that reperfusion of a pancreaticoduodenal graft can be estimated using duodenal pHi and that the ratio of irCT at 10 and 60 min gives an indirect estimate of pancreatic reperfusion. The results also show that grafts stored in EuroCollins reperfuse more slowly than grafts stored in Perfadex. PMID- 1738925 TI - Renal transplant function after ten years of cyclosporine. AB - Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity. PMID- 1738926 TI - The incidence and impact of early rejection episodes on graft outcome in recipients of first cadaver kidney transplants. AB - The objective of this study was to define the incidence and significance of acute rejection occurring in the first year following transplantation. The influence of contemporary induction immunosuppression on rejection, as well as the effect of rejection on graft and patient loss, renal function, and maintenance immunosuppression during the first year in 110 recipients of first cadaver renal transplants were analyzed. All patients received CsA, Aza, and prednisone for 30 days with withdrawal of Aza at 30 days and then prednisone at 105 days; 57 patients were prospectively randomized to receive ALG (Merieux) until serum creatinine was less than 300 mumol/L. Short-term ALG administration did not influence the incidence, severity, nature, or outcome of rejection episodes. Fifty-five (50%) patients had at least 1 rejection in the first 90 days. All patients with delayed graft function and 7/8 (88%) sensitized patients (current PRA greater than 50%) had at least 1 rejection episode; 71% (n = 35) of all rejection episodes occurred in the first 30 days posttransplant. Patients rejection free at 90 days remained rejection free the entire first year. Graft loss was 18% for rejections in the first month, 13% for rejections occurring later (P = NS); 20% (n = 11) of patients had a second rejection and 1% (n = 2) had a third rejection. The risk of graft loss was 9% with a first rejection, 38% with a second rejection, and 50% with a third rejection. Of 12 (22%) rejections that were steroid resistant, 10 (83%) were reversed with OKT3. One-year graft survival for patients without rejection, with steroid-sensitive rejection, and with steroid-resistant rejection was 96%, 88% (P = ns), and 58% (P less than 0.001), respectively; 1 year SCr was 168 +/- 93, 196 +/- 77 (P = ns), and 268 +/- 96 microMol/L (P less than 0.05), respectively. Patients free of rejection and with stable renal function continued to do well on maintenance CsA monotherapy, and they were more likely to be on CsA monotherapy than those with rejection episodes (P less than 0.01). PMID- 1738927 TI - Enisoprost in renal transplantation. The Enisoprost Renal Transplant Study Group. AB - Prostaglandins of the E-series (PGE) mediate a wide variety of physiologic processes and have been shown to have regulatory roles in cell immunity. Previous animal and human trials have shown lower incidence of acute rejection when prostaglandins are administered in conjunction with standard immunosuppressives. This study evaluated the effects of the PGE analogue, enisoprost (EP), in a multicenter (39 centers) prospective, randomized, double-blind trial in 374 patients undergoing renal transplantation. Groups were placebo, enisoprost 50 micrograms p.o. q.i.d. (EP-50 micrograms), and enisoprost 100 micrograms p.o. q.i.d. (EP-100 micrograms). Patients received cyclosporine, azathioprine, corticosteroids, and Minnesota antilymphocyte globulin or OKT3 according to each center's protocol. Prophylactic antibody therapy (MALG or OKT3) was not randomized. Two hundred fifty-five patients completed the 8-week study period. Of the 119 patients who were withdrawn, 73 did so because of an adverse event. Rejection episodes occurred in 98 of 374 patients (26%). There was no statistically significant difference in the incidence of rejection between placebo- and EP-treated patients (P = 0.782). There was no significant difference in episodes of cyclosporine nephrotoxicity between placebo- and EP-treatment groups (P = 0.883). There was also no difference between incidence of acute tubular necrosis, duration of initial hospitalization, or need for rehospitalization between placebo- and EP-treated groups. Administration of EP was associated with frequent adverse events including elevation of body temperature, dyspepsia, and diarrhea. Antibody-treated patients had a higher percentage of black recipients, higher mean body weight, greater cold ischemic times, fewer living-related donors, and higher panel reactivity. Patients not receiving antibody prophylaxis were better matched immunologically than those receiving either MALG or OKT3. Despite these immunologic differences, there was no significant difference in the incidence of rejection in patients who did or did not receive antibody prophylaxis. Cyclosporine toxicity was more common in MALG-treated patients (P = 0.02). Renal function was worse in antibody-treated patients. There was no detectable effect of enisoprost on the incidence of acute rejection, renal function, or hospitalization in a multicenter prospective, randomized, double-blind trial in 374 patients undergoing renal transplantation. PMID- 1738929 TI - The impact of HLA frequency differences in races on the access to optimally HLA matched cadaver renal transplants. The Medical Advisory Committee. AB - We examined the donor/recipient HLA match of 448 consecutive cadaver renal transplants to determine if donor race had an impact on the quality of HLA match that was achieved. Eighty (17.9%) kidneys from black donors and 368 (82.1%) from nonblack donors (87.8% caucasians) were distributed to the blood type compatible and crossmatch negative recipients on the basis of a local variance of the United Network for Organ Sharing (UNOS) point system. There were 278 (62%) nonblack and 170 (38%) black recipients, numbers close to those of nonblacks and blacks on the waiting list (59% and 41%, respectively). Kidneys from nonblack donors represented 86% (240/278) of transplants for nonblack and 75% (128/170) of transplants for black recipients. The best matches, i.e., zero-A,B,DR, zero-A,B, zero-B,DR, and 1-A,B,DR mismatches, for nonblack recipients were solely derived from the nonblack donors, and the few well-matched kidneys from black donors were distributed to black recipients. Black recipients with zero mismatches were few (3, 2%) compared with nonblacks (21, 8%). Kidneys received by black recipients were more likely to be poorly matched (5-6 mismatches) if coming from nonblack donors (57/128, 44%) than black donors (11/42, 26%), P = 0.035. It was also observed from HLA frequency comparisons that well-matched kidneys from nonblack donors were rarely distributed to black patients with HLA phenotypes unique to or more common in blacks who represented a sizeable portion of blacks on the waiting list. We conclude that better donor/recipient HLA matches are achieved when both donors and recipients are of the same race. Thus a larger number of black donors are needed to improve the quality of HLA matching for potential black kidney transplant recipients. PMID- 1738928 TI - The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation. AB - Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events. PMID- 1738930 TI - The large center variation in half-lives of kidney transplants. AB - Based on a log-linear model for analyzing multiple effects, center variation in the UCLA Transplant Registry is the most influential factor in early renal graft survival. Among 68 active centers accounting for 70% of all transplants between 1985 and 1989, the 1-year graft survival (adjusted for 15 covariates) varied from 60 to 90%. The long-term graft survival, as measured by the half-lives of the first cadaver donor transplants at these centers, based on a minimum of 4 years of follow-up data, varied from 3 to 26 years. Although there was some correlation (r = 0.24) of half-life with the 1-year graft survival rate at each center, in many instances, excellent centers had poor half-lives and average centers had excellent half-lives. From a Cox regression analysis on data from 6752 first cadaver-donor renal transplants surviving beyond 1 year (submitted to the UNOS data base), white female recipients of 0 HLA-AB-mismatched kidneys not requiring dialysis in the first week posttransplant had projected half-lives of 14.1 years, whereas black male recipients of 4 HLA-AB-mismatched kidneys requiring therapeutic dialysis had half-lives of 2.3 years. However, adjustment for these factors could only remove 17% of the total variability in the centers' half lives. Consequently, any algorithm intended to judge a center's renal transplant capabilities should include, even after adjustment for covariates, some function of both 1-year graft survival and half-life beyond 1 year. PMID- 1738931 TI - The effect of erythropoietin and blood transfusions on highly sensitized patients on a single cadaver renal allograft waiting list. AB - The effects of EPO on transfusion requirements and HLA allosensitization were studied in a group of 145 sensitized patients on a single cadaveric renal allograft waiting list. All patients included in the study had PRA levels greater than 40% and at least six months of follow-up after the general availability of EPO. A total of 108 (74%) of these patients received EPO during the study period while 37 (26%) did not. The EPO patients had a much higher incidence of prior transfusions than the non-EPO patients (64% vs. 39% P less than 0.05). During the follow-up period, there was a marked reduction in transfusion incidence in the patients who received EPO from 64% to 14% (P less than 0.05). A lesser and nonsignificant reduction in incidence of transfusions was seen in the non-EPO-EPO patients. Analysis of PRA levels in the EPO and non-EPO groups demonstrated a reduction in PRA levels over time but there was no difference between the two groups. When the patients were divided by the need for transfusions in the follow up period, a comparison of these two groups demonstrated significant differences. At the six-month follow-up point, patients in the nontransfused group had a significantly lower mean PRA than the transfused patients (49% vs. 62%, respectively, P less than 0.05). Furthermore, a greater number of patients in the nontransfused group had PRA declines greater than or equal to 15% compared with the nontransfused group (56/46% vs. 4/15%, respectively; P = .007). Stepwise logistic regression analysis of possible risk factors for persistent high PRA levels demonstrated that continued transfusion was the only significant factor. This study suggests that the institution of EPO therapy in sensitized patients on a single cadaveric waiting list can result in substantial reduction in the need for on-going transfusions. However, the decline in PRA levels appears to be more closely tied to the avoidance of transfusion rather than to the specific institution of EPO therapy. PMID- 1738932 TI - Cadaveric small bowel and small bowel-liver transplantation in humans. AB - Five patients had complete cadaveric small bowel transplants under FK506 immunosuppression, one as an isolated graft and the other 4 in continuity with a liver. Three were children and two were adults. The five patients are living 2-13 months posttransplantation with complete alimentation by the intestine. The typical postoperative course was stormy, with sluggish resumption of gastrointestinal function. The patient with small intestinal transplantation alone had the most difficult course of the five, including two severe rejections, bacterial and fungal translocation with bacteremia, renal failure with the rejections, and permanent consignment to renal dialysis. The first four patients (studies on the fifth were incomplete) had replacement of the lymphoreticular cells in the graft lamina propria by their own lymphoreticular cells. Although the surgical and after-care of these patients was difficult, the eventual uniform success suggests that intestinal transplantation has moved toward becoming a practical clinical service. PMID- 1738933 TI - The use of marginal donors for liver transplantation. A retrospective study of 365 liver donors. AB - A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from "marginal" donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donor's weight above 100 kg was the only variable found to be associated with both significantly increased 3 month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (greater than 15 micrograms/mg/min), but not each of these variables itself, was also associated with a significantly increase rate of hepatocellular damage (P less than 0.001). All other variables, including age greater than 50, ischemic time greater than 12 hr, combined liver-pancreas procurement, and liver function test abnormalities, did not affect the outcome. We conclude that extending our limits to accept donors of the higher age group and those who have moderately abnormal liver function tests or a prolonged ischemic time will not jeopardize our results. It is suggested to perform liver biopsy in overweight donors during the retrieval to prevent using grafts with severe fatty infiltration. It is hypothesized that hormonal changes, starvation, and increased risk to develop infection might jeopardize the outcome of grafts from donors with a prolonged ICU stay. Although 70% of the early hepatocellular injuries are reversible, the remaining 30% result in graft failure. PMID- 1738934 TI - Biliary complications in pediatric liver transplantation. A comparison of reduced size and whole grafts. AB - One of the major changes in liver transplantation has been the application of reduced-size liver transplants(RLT). RLT has the great advantage of expanding the donor pool up to ten times the weight of the recipient, thereby decreasing pretransplant mortality in the pediatric age group. It has been suggested that RLT is a risk factor for biliary complications. To analyze the role of RLT and biliary complications, the results of 213 consecutive liver transplants in 164 pediatric patients over a 6-year period will were reviewed. These included 113 whole-liver transplants and 100 reduced-size liver transplants (49 reduced cadaveric liver transplants (RCLT), 38 split-liver transplants (SLT) and 13 living-related liver transplants (LRLT). The average weight and age were significantly higher in recipients receiving whole-size grafts (average weight 18.4 mg, average age 4.9 years) than in those receiving reduced size grafts (average age 2.3 years, average weight 11.1 kg). Biliary reconstruction consisted of Roux-en-Y, cholangiojejunostomy (n = 203) or choledochocholedochostomy (n = 10). There were 29 total biliary complications, (13.6%) with no significant difference in the complication rate between the whole (n = 13, 11.5%) or reduced livers (n = 16, 16%). Biliary leakage was the most common complication (n = 20), and it occurred at the biliary enteric anastomoses (n = 10), the roux limb (n = 7), or at the cut edge (n = 3). Of the leaks occurring at the biliary enteric anastomoses, 50% were caused by hepatic artery thrombosis. Biliary obstruction accounted for their remaining complications (n = 9) or 4.2%. Actuarial survival from 6 years to a minimum of two months of follow-up was 73% in the whole-size and 70% in reduced-size liver transplants. This series demonstrates that the incidence of biliary complications is similar in reduced-size and full-size grafts. No grafts were lost to biliary complications in the absence of hepatic artery thrombosis. PMID- 1738935 TI - Hepatic artery thrombosis in infants. A comparison of whole livers, reduced-size grafts, and grafts from living-related donors. AB - Hepatic artery thrombosis (HAT) is a major cause of patient morbidity and graft loss in pediatric liver transplantation (OLT). Although some grafts may be salvaged by arterial thrombectomy and reconstruction, many patients require retransplantation. Patient survival is reduced by HAT. It has been suggested that the incidence of HAT may be altered by the use of reduced-size grafts (RSG). We analyzed our series of infants receiving OLT to determine the frequency of HAT in full-size OLT, cadaveric RSG, and living-related RSG. The role of arterial anastomotic technique in the development of HAT was also examined. Between 10/1/84 and 12/7/90 433 liver transplants were performed. During this period 100 patients between 3 months and 2 years of age (mean 13 months) received 134 liver grafts. The mean weight at the time of transplant was 7.9 kg. (range: 1.9-15 kg). Of the 134 grafts, 60 were whole livers, 61 were cadaveric RSGs, and 13 were living-related RSGs. The cadaveric RSGs were 9 right lobe grafts, 21 left lobe grafts, and 31 left lateral segment grafts. Twenty-seven of the cadaveric RSGs were from split livers, while the other 34 were simple reductions. All 13 living related RSGs were left lateral segments. HAT occurred in 15 of 60 (25%) whole livers, 9 of 61 (15%) cadaveric RSGs, and 3 of 13 (23%) of the living-related donor RSGs (P = NS). Subdividing the cadaveric RSGs revealed that HAT occurred in 3 of 9 (33%) right lobe grafts, 3 of 21 (14%) left lobe grafts, and 3 of 31 (10%) left lateral segment grafts (P = NS). The site of the arterial anastomosis in the recipient correlated with the incidence of HAT (hepatic artery 21/86 [24%], celiac axis 1/9 [11%], aorta 2/32 [6%], P = 0.06). In conclusion, it appears that use of a cadaveric left lobe or left lateral segment graft and an aortic arterial anastomosis reduces the risk of hepatic artery thrombosis in liver transplant recipients less than 2 years of age. PMID- 1738936 TI - Human islet isolation and allotransplantation in 22 consecutive cases. AB - This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patients had plasma C-peptide greater than 3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparation were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to greater than 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function. PMID- 1738937 TI - Whence the lungs? A study to assess suitability of donor lungs for transplantation. AB - Efforts at clinical lung transplantation have been hampered by an insufficient donor pool. To estimate the number of potential suitable lung donors, we conducted a UNOS-sponsored survey of organ procurement organizations and collected data with respect to possible lung donation from human cardiac donors. Contact with OPOs was made by telephone after cardiac donors were identified by UNOS. Of 150 cardiac donors, 7 were utilized for lung or heart-lung transplantation. By our criteria, however, 47 additional donors had lungs that may have been suitable for transplantation but were not utilized, and frequently were not offered for transplantation for a variety of reasons. This survey implies that approximately 25% of cardiac donors likely have lungs that may be suitable for transplantation. PMID- 1738938 TI - Social rehabilitation and return to work after cardiac transplantation--a multicenter survey. AB - As the medical results of heart transplantation steadily improve, the social rehabilitation of patients, in particular, their ability to return to some form of employment, is becoming increasingly important. Two-hundred fifty patients were therefore surveyed at 7 heart transplant centers (5 of which were Medicare certified) from different geographic regions in the U.S.A. Over all, 45% were employed, 36% were unemployed, 13% were medically disabled, and 6% were retired. Of those employed, 87% had returned to their previous employment, and only 13% had secured new employment. Of the unemployed, 16% had made job applications, and no fewer than 63% had no current plan to seek employment. Factors found to negatively influence a return to work included the following: (1) length of medical disability prior to transplantation; (2) a patient's self-perception of being physically unable to work; and (3) the potential loss of health insurance and/or disability income. At 2 centers, where there was a definite policy of not supporting a patient's claim for medical disability in the absence of an absolute indication, there were significantly increased numbers who (1) secured new employment and (2) planned to seek employment. More serious attention must be paid to aspects of employment if heart transplant recipients are to become fully productive members of the community. PMID- 1738939 TI - HLA in human serum--quantitation of class I by enzyme immunoassay. AB - A solid-phase, enzyme-linked immunoassay was used to quantitate the soluble fraction of HLA-class I. The sera of 318 individuals were studied, as well as the urine of six individuals with normal renal function. The stability of blood concentrations of the soluble HLA was also evaluated. The data justify the following six conclusions. (1) All normal people have circulating HLA (mean = 357 ng/ml). (2) The population can be divided into one group of low secretors (mean = 162.4 +/- 65.2 ng/ml) and another group of high secretors (mean = 540.7 +/- 185.9 ng/ml) (P less than 0.01). (3) Blood levels in each individual are reasonably consistent over short (days) and long (years) periods of time. (4) The mean concentration of soluble HLA-class I in all renal failure patients was 590 ng/ml, significantly higher than normal (P = less than 0.05); it was highest in patients on peritoneal dialysis (mean = 683 ng/ml) in spite of substantial chronic loss in peritoneal dialysate. (5) Renal allograft recipients with stable allograft function also had mean values greater than normal at 554 ng/ml (P less than 0.05). (6) Soluble HLA-class I was not detected in the urine of individuals with normal renal function. PMID- 1738940 TI - Intragraft cytokine profile during human liver allograft rejection. AB - Forty-three human liver allograft biopsies and normal liver were directly analyzed for inflammatory and immunoregulatory cytokine gene expression by polymerase chain reaction (PCR). IL-5 gene expression was predominantly present in biopsies from liver allografts with histopathological evidence of acute rejection. IL-2 gene expression was rarely observed in rejecting allografts or allografts without evidence of rejection. In contrast, IL-4 message was readily detectable in the majority of liver allografts regardless of clinical status. The inflammatory mediators IL-1 beta, TNF-alpha, and IL-6 were detected with similar frequency in rejecting allografts and allografts without evidence of rejection. These findings suggest that inflammatory and immunoregulatory cytokines are produced within the allograft. Moreover, IL-5 may play a role in the local mechanisms of liver allograft rejection. PMID- 1738941 TI - Assessment of the in vivo immunosuppressive activity of the major cyclosporine metabolite by leukemia allograft rejection. AB - AM1 (M17) is the major metabolite of cyclosporine found in the blood of human transplant recipients, and trough levels of this derivative exceed those of the parent compound approximately two-fold. Studies performed in vitro indicate that AM1 retains only 10-20% of the biological activity of the parent compound, but very little is known about its in vivo immunosuppressive effects. We therefore developed a rapid and sensitive method, based on the rejection of allogeneic L1210 (H-2d) leukemia cells by C57BL/6 (H-2b) mice, to assess the immunosuppressive activity of AM1 in vivo. Rejection of the leukemia allograft was determined by analyzing the spleens from mice injected intravenously with 10(5) L1210 cells for the presence of H-2Kd-positive cells by flow cytometry using an FITC-conjugated monoclonal anti-H-2Kd antibody. Nonimmunosuppressed mice rejected the allogeneic cells and survived indefinitely. Spleens from these mice were virtually free of H-2Kd-positive cells (0.51 +/- 0.21%) by day 7. In contrast, C57BL/6 mice treated with 10 mg/kg/day s.c. of CsA all died from the L1210 challenge (mean survival time of 9 +/- 1 days). Spleens from mice treated in this manner contained 11.02 +/- 3.31% H-2Kd-positive cells on day 7. There was a direct correlation between the dose of CsA administered (7.5-50 mg/kg/day) and the percentage of H-2Kd-positive cells in the spleen. We then compared the immunosuppressive activity of AM1 and CsA in this model. AM1 was purified from the urine of CsA-treated renal allograft recipients by a combination of preparative adsorption-desorption chromatography and preparative elution high performance liquid chromatography. AM1 at a dose of 10 mg/kg/day exhibited no demonstrable immunosuppressive effect, and trough levels of AM1 on day 7 were only 36 +/- 4 ng/ml. Increasing the dose of AM1 to 50 mg/kg/day resulted in only 1.05 +/- 0.16% H-2Kd-positive cells in the spleens (P = NS) and a mean trough level of 221 +/- 27 ng/ml. In contrast, mice treated with 50 mg/kg/day of CsA exhibited 17.7 +/- 2.9% H-2Kd-positive cells in their spleens and a mean trough CsA level of 3036 +/- 277 ng/ml. The half-life of a single subcutaneous dose of 10 mg/kg of AM1 (4.6 hr) was significantly shorter than that of CsA (9.7 hr) in mice. Compared with CsA, the lack of immunosuppressive effect of AM1 in vivo therefore appears to be due to a combination of decreased immunosuppressive activity and increased rate of clearance in mice. PMID- 1738942 TI - Skin xenograft rejection in Xenopus--immunohistology and effect of thymectomy. AB - Immunohistology, using the T-lineage-specific monoclonal antibody XT-1 and an anti-IgM mAb, illustrates differences in the cellular basis of skin allograft and xenograft destruction displayed by control froglets (X. laevis). Thus T cells predominate within allografts, whereas B-lineage cells accumulate under xenografts (from X. tropicalis). The possibility that T cells do not play a central role in mediating xenograft rejection is consistent with the finding that early thymectomy (at 7 days) has minimal effect on rejection end points of X. tropicalis transplants. However, rejection of skin from a "phylogenetically less distant" xenogeneic species (X. borealis) is shown here to be impaired in early thymectomized X. laevis. Differences in the extent to which the thymus has been shown to influence skin xenograft rejection in Xenopus are discussed. PMID- 1738943 TI - Comparison of UW and Euro-Collins solutions in paired cadaveric kidneys. PMID- 1738944 TI - Whole-organ transplant of an annular pancreas. PMID- 1738945 TI - Recurrent variceal bleeding after liver transplantation--persistent left-sided portal hypertension. PMID- 1738946 TI - A major difference in the mechanisms of neonatally induced tolerance and cyclophosphamide-induced tolerance. PMID- 1738947 TI - Hemostasis at the time of renal transplantation for bleeding following core biopsy. PMID- 1738948 TI - [Mandatory ambulatory labor]. PMID- 1738949 TI - [The main obstetrical problems]. AB - Development og antenatal care and obstetrics in Denmark during the past decades has been carried out by distribution of advisory guiding principles from the Ministry of the Interior (Ministry of Health) and the Board of Health, most recently in 1985. On the basis of a review of the current problems in obstetrics, reassessment of the guiding principles is suggested, particularly development of obstetrics on the basis of well controlled assessments of new possibilities. As possibilities for improving the results of obstetrics, the problems concerning preconceptional examination, alternative methods, mini-centre arrangements, care of sick pregnant women in their own homes, employment of ultrasound and cardiotocography are described. Modern furnishing of maternity departments, improved midwifery and better cooperation between the staff groups involved are considered necessary to ensure that maternity care in Denmark can become even better than it is at present. PMID- 1738950 TI - [The course of postpartum period after mandatory ambulatory labor]. AB - Mandatory early discharge for all normal multiparae was introduced as a trial arrangement in the County of Ringkobing from 1.1.1990. A total of 113 early discharged women and 90 patients who remained in hospital participated in a questionnaire investigation comprising 41 questions about problems and need for support during the first postpartum period and about satisfaction with the postpartum period. A total of 64% of all the multiparae were early discharged and were discharged 4.2 hours after the delivery. On the whole, the women were satisfied with the postpartum period and only few problems in infants or mothers occurred. The early discharged group, however, as compared with the control group, stated that they had received less satisfactory support concerning breast feeding (p less than 0.005) and that, in general, they had received less support from friends (p less than 0.01) and hospital staff (p = 0.04). The group of early discharged felt that they had received less satisfactory information (p less than 0.005) and, on the whole, they were less satisfied with the postpartum period (p less than 0.005). In addition, the group who were early discharged had 67% more telephone conversations with and 127% more visits from the midwife, health nurse or practitioner. PMID- 1738951 TI - [Strategy for delivery in breech presentations. A retrospective study]. AB - A six-year material of 236 singleton breech deliveries at term was evaluated retrospectively. Infants who were small for the gestational ages at birth were excluded. Vaginal delivery proved successful in 41.1% of the material. The vaginal success rate was 61.8. Low parity and age and high birth weight reduced the vaginal success rate. The route of delivery did not affect the outcome in terms of infantile morbidity or mortality. Nevertheless, an increased number of neonates with congenital disorders was observed. It is concluded that trial of vaginal delivery may be employed in a selected group of pregnant women with breech presentations without increasing the risk of adverse effects of the neonate. PMID- 1738952 TI - [Xerostomia caused by radiotherapy of patients with head and neck cancer]. AB - Xerostomia causes great inconvenience in patients treated with irradiation for cancer of the head and neck. For all practical purposes, salivary gland tissue becomes irreversibly incapable of functioning after doses of 40 Gy (standard fractioning). Curative doses are 60-70 Gy and, therefore, xerostomia can only be limited by attempting to involve as little as possible of salivary gland tissue in the irradiation fields. The limits of the tumour should be diagnosed as exactly as possible so that the irradiation fields are not made any larger than necessary "for safety". Therapeutic techniques which involve salivary gland tissue on only one side should be elected when this is justifiable. It is important to inform the patient about caries prohylaxis and the patient's own dentist should be involved in the problem as early as possible. Prophylatic fluorine treatment should be offered to alle of the patients. PMID- 1738953 TI - [Self assessment of the functional level in a group of psychiatric patients on admission and discharge. Aspects of the reliability of the Sickness Impact Profile]. AB - A comparison was undertaken between a method of personal assessment of the functional level and the health related quality of life, the Sickness Impact Profile (SIP) and a method based on observers, the Nurses' Observation Scale for Inpatient Evaluation, in a little group of mentally ill patients. This revealed good sensitivity as regards the registered effect of treatment and fairly good agreement between the results. SIP has gradually been demonstrated to be a well proved and widely employed method within many medical specialties with both internal and external validity. PMID- 1738954 TI - [Differential diagnosis in acute chest pain and suspected myocardial infarction. A pilot study]. AB - In half of the patients admitted with chest pain on suspicion of an acute myocardial infarction (AMI), this diagnosis is not confirmed (non-AMI). Both AMI and non-AMI patients have a mortality which exceeds the mortality of the background population in the years following discharge based on a high incidence of cardiac death. As a pilot investigation, a comprehensive investigation programme was tested in 32 consecutive non-AMI patients. The possible organic causes of acute chest pain were thus illustrated systematically in each individual patient. In ten of the patients, a definitive diagnosis was established within the first 24 hours of admission and no further investigation was thus performed. The remaining 22 patients participated in the planned investigation programme. In 30 of the patients (94%) a probable organic cause for the chest pain was found. This investigation demonstrates that the investigation programme is employable and it suggests that the cause of chest pain in non-AMI patients usually can be placed in one of the three main groups: 1) IHS, 2) oesophageal disease and 3) physiurgic conditions. PMID- 1738955 TI - [Formaldehyde in textiles as a possible cause of arthritis and angioedema]. AB - A case of arthritis and angioedema which developed on occupational exposure to formaldehyde in textiles is described. Possible pathological mechanisms are discussed. The suspicion that an unknown immunological reaction may be the cause is raised. PMID- 1738956 TI - [Pyomyositis]. AB - Pyomyositis (PM) is characterized by bacterial infection and suppuration of striated muscle. It is very rarely encountered in temperate climates. Only five cases have hitherto been reported in Denmark. Two cases of PM are presented. Both of these demonstrate the difficulty of establishing early diagnosis and the severe complications of PM. PMID- 1738957 TI - [Crisis intervention--a task for the district psychiatry?]. PMID- 1738958 TI - Coxarthrosis on the island of Gotland. Increased prevalence in a rural population. AB - On the island of Gotland and in the city of Malmo, the prevalence of coxarthrosis was calculated using the hip projections in colon roentgen examinations. The prevalence of coxarthrosis among the Gotland islanders was about twice that of the Malmo urbanites, and the condition became obvious earlier in life. The population of the local Gotland city of Visby did not contribute to this difference; the difference was entirely due to an increased incidence in the rural population of the island. Heavy labor in conjunction with farming is believed to be the cause of the deviation. PMID- 1738959 TI - Uptilting osteotomy of the lateral tibial plateau for a knee deformity. A case report. AB - A middle-aged woman had had anterior poliomyelitis at 11 years of age that had left her with residual weakness in both legs. She gradually developed a recurvatum and valgus deformity in both knees, which caused pain and instability. A technique to restore the top of the tibia by means of a rotational osteotomy of the lateral tibial plateau is presented. This operation resulted in painless, asymptomatic knees and improved function. PMID- 1738960 TI - Posttraumatic ulnar translation of the carpus. A case report. AB - A 24-year-old miner sustained wrist trauma in a car accident. The initial radiographs showed a dorsal rim fracture of the radius without any dislocation of the wrist. Fourteen days later, radiography revealed a total ulnar translation of the carpus. Open reduction was performed with a good clinical and radiographic result. PMID- 1738961 TI - Simultaneous occurrence of trapezium-scaphoid-trapezoid dislocation and multiple carpometacarpal fracture dislocations. A case report. PMID- 1738962 TI - Mixing does not improve mechanical properties of all bone cements. Manual and centrifugation-vacuum mixing compared for 10 cement brands. AB - Contemporary mixing methods--centrifugation, vacuum mixing with or without precompression--were compared with manual mixing by testing strength characteristics in accordance with a proposed revision of the international standard for bone cements as applied to 10 cement brands. Simplex brands and low viscosity cements were the strongest, and were not improved by any of the vacuum mixing procedures. Centrifuging was found unsuitable for low-viscosity cements. Without attaining the strength of the former, the cements best suited for auxiliary mixing methods were CMW-1 and Palacos brands, which improved 6-11 percent by either of the methods. The Sterivac system was generally found unacceptable, because about 20 percent of a cement package was retained in the mixing gear, and the application of precompression had no additional effect on compressive and bending strengths. PMID- 1738963 TI - Cefuroxime for prevention of postoperative coxitis. One versus three doses tested in a randomized multicenter study of 2,651 arthroplasties. AB - Infection prophylaxis in hip replacement with one perioperative dose of cefuroxime was evaluated in a randomized controlled multicenter study using a three-dose regimen as a control. All the operations were performed in conventionally ventilated operating theaters. Of the 2,796 hip replacements entered in the study, 145 replacements were excluded because of protocol violations. The remaining 2,651 hip replacements were analyzed: 1,327 and 1,324 in the one- and the three-dose group, respectively. There were no differences between the one-dose and the three-dose groups as regards the incidence of postoperative wound-healing problems, and urinary tract or other distant infections. The use of additional antibiotics after the perioperative prophylaxis did not differ between the treatment groups. After a mean follow-up period of 13 months, joint sepsis was diagnosed in 11 of the patients in the one-dose group (0.83 percent) and in 6 of the patients in the control group (0.45 percent). This difference was not significant. Because the estimated difference between the one dose and the three-dose group was 0.38 percent, we could not confirm that the efficacy of one dose was equal to three doses. An extended follow-up study, with more cases of joint sepsis, may provide more conclusive data. Until then, a three dose regimen is recommended. PMID- 1738964 TI - The irritable hip. Scintigraphy in 192 children. AB - Over a 4-year period, 192 patients with a typical transient synovitis syndrome underwent radionuclide scintigraphy shortly after presentation. Three different patterns were found suggesting that all the cases may not be of the same etiology. Fifteen patients had evidence of ischemia of the femoral head, but only 4 patients went on to develop the typical radiographic features of Perthes' disease. The other 11 patients are thought to represent a minor, radiographically silent form of Perthes' disease. PMID- 1738965 TI - Femoral anteversion in normal adults. Ultrasound measurements in 50 men and 50 women. AB - The femoral anteversion (AV) angles were measured by ultrasound in a normal group of 100 adult subjects to find the normal range of anteversion, to determine the normal left/right difference, to assess the interobserver variation, and to find the correlation between AV angle and clinical hip rotation. All the ultrasound measurements were performed independently by 2 observers. The mean AV angle was 18 degrees in the women and 14 degrees in the men. The mean left/right difference in AV was 3.8 degrees, and the upper normal limit of side difference (mean +/- 2 SD) was 9.8 degrees. The mean (SD) interobserver variation was only 1.9 degrees (1.3 degrees). The correlations between AV angles and internal and external hip rotation were significant, but not very high (r = 0.49 and -0.49, respectively). We conclude that ultrasound is appropriate for measurement of femoral anteversion. Our results could be used as a basis when evaluating patients with clinically suspected rotational disorders of the femur. PMID- 1738966 TI - The displacement of the femoral head by rotational acetabular osteotomy. A radiographic study of 97 subluxated hips. AB - To determine the limits of medial and inferior displacement of the subluxated femoral head by rotational acetabular osteotomy, we studied the acetabular coverage and position of the femoral head radiographically before and after surgery in 97 hips. The median age of the patients at the time of surgery was 33 (18-54) years. The position of the femoral head was represented by its center and medial and upper borders. The average increase and decrease in the CE and the AC angle were 39 degrees and 27 degrees, respectively. The average medial displacement of the head was 8 (-12 to +19) mm measured from its center, and 7 ( 10 to +21) mm measured from its medial border. The average inferior displacement was 5 (-6 to +19) mm from its center and 4 (-10 to +15) mm from the upper border. These results indicate that concentric reduction by rotational acetabular osteotomy is limited and that medial displacement of the subluxated femoral head is within similar ranges obtained by other conventional pelvic osteotomies. PMID- 1738967 TI - Osteonecrosis of the femoral head in spontaneously hypertensive rats. Relation to ossific nuclei during growth. AB - We observed the distribution of the ossific nuclei and the occurrence of osteonecrosis in the femoral capital epiphysis of spontaneously hypertensive rats. In 270 femoral heads, the ossific nuclei were seen in the following sites of the epiphysis: Type 1, the lateral portion in 150 femoral heads; Type 2, the central portion in 5 heads; Type 3, both lateral and central portions in 12 heads; and Type 4, throughout the epiphysis in 62 heads. The number of femoral heads with osteonecrosis in Types 1-4 was 61, 0, 5, and 17, respectively. PMID- 1738968 TI - Oral cefadroxil prophylaxis in hip fracture surgery. Serum concentrations studied in 17 patients. AB - Serum concentration-time curves were determined in seventeen 82 (60-90) year-old patients undergoing trochanteric hip fracture surgery after receiving 1 g of cefadroxil per os. All the patients attained a serum level of antibiotic high enough to inhibit the growth of Staphylococcus aureus and S. epidermidis. When orally administered, cefadroxil should be given within 2 hours before surgery. PMID- 1738969 TI - Uppsala screws or Hansson pins for internal fixation of femoral neck fractures? A prospective study of 180 cases. AB - In a prospective randomized trial, two methods of internal fixation of femoral neck fractures were compared. Totally, 179 patients with 180 fractures were treated with either two Uppsala screws (n 96) or two Hansson pins (n 84). In all, 130 fractures were primarily displaced (Garden stages III and IV), whereas 88 percent of the fractures in both groups were well reduced. The patients were followed clinically and radiographically for 1 year. Thirty-six patients died within 12 months after the operation. The functional results and the incidence of segmental collapse and nonunion did not differ between the groups. However, at the 4-month follow-up, 2 of 59 of the Garden's stages III and IV in the Uppsala screw group were found displaced, whereas the corresponding result in the Hansson pin group was 9 of 52 (P = 0.03). PMID- 1738970 TI - Implant holding power of the femoral head. A cadaver study of fracture screws. AB - The holding power against axial pull-out forces of eight different screws implanted in the femoral heads of cadavers was tested. The Olmed screw had the greatest resistance to pull-out forces followed by the recently designed Ullevaal screw with long threads, and the von Bahr screw. There were substantial differences in the holding power in the four sectors of the femoral head. The holding power was strongly correlated with the logarithm of the moment of inertia of the screw threads, which is a function of the area and number of the threads (r = 0.94, P = 0.0002). PMID- 1738971 TI - Fractures of the femoral shaft in children treated with an AO-compression plate. Report of 12 cases followed until adulthood. AB - Thirteen femoral shaft fractures in 12 children aged 0-15 years were each treated with an AO-compression plate. The mean age at operation was 11 (6-14) years, and all the patients were followed until closure of the growth plates. No deep infections occurred, and all the fractures healed without angulation of rotation. The mean overgrowth was 7 (-9-25) mm. All the patients had unrestricted movement in the hip and knee, and had no complaints at the follow-up examinations. We conclude that plate osteosynthesis of femoral shaft fractures in children is a safe and reliable method for internal fixation when use of traction is not possible. PMID- 1738972 TI - Retrofascial pyogenic iliac fossa abscess. 20 cases studied by ultrasonography. AB - Twenty patients with a pyogenic iliac fossa abscess were analyzed. The main clinical signs were fever, limp, pain, and flexion deformity of the hip. Ultrasonography was a reliable diagnostic test. PMID- 1738973 TI - Treatment of 84 cases of femoral nonunion. AB - Eighty-four femoral nonunions were treated with Kuntscher nailing, Grosse-Kempf locked nailing, plating, and Huckstep nailing, and were followed-up for a median of 34 months. Kuntscher nailing and locked nailing were superior, with fewer complications, less operation time, and less blood loss. A Kuntscher nail was preferred for the isthmic region when there was no shortening of the bone, and a locked nail was preferred above or below this region or when lengthening was indicated. PMID- 1738974 TI - Effects of intramedullary reaming and nailing on blood flow in rat femora. AB - The right femur in 40 rats was reamed, and in 40 others it was additionally nailed. Analysis of bone blood flow was performed by the distribution of radiolabeled microspheres at different postoperative time intervals. Blood-flow measurements were accompanied by analyses of hydroxyproline and calcium contents. Immediately after reaming, the blood flow of the diaphyseal part of the femur was reduced to approximately one third of that of the intact femur, whereas the contents of hydroxyproline and calcium were reduced by 10 percent. Within 1 week, the blood flow was normal. This study provides evidence that the presence of a nail does not interfere with the restoration of bone blood flow. Restoration of blood flow in bone apparently is a rapid process. The replacement of hydroxyproline and calcium contents seemed to be linked to flow, as no increase in these constituents were found until the blood flow had approximated the level of the intact femur. PMID- 1738975 TI - Biodegradable guide for bone regeneration. Polyurethane membranes tested in rabbit radius defects. AB - Segmental, 1-cm osteoperiosteal defects were produced in both radii of 10 rabbits. One defect was covered with a biodegradable polyurethane membrane formed as a tube. The contralateral defect served as an untreated control. Healing was analyzed by radiographic and histologic studies after 5 weeks. Nine out of 10 control defects displayed nonunion, whereas membrane-treated defects consistently healed by forming callus external to the membrane fusing the bone fragments. Loose connective tissue was predominant in the bone gap underneath the membrane. Presumably, the membrane has served as a scaffold for regenerating periosteum. PMID- 1738976 TI - Renal function not impaired by hip arthroplasty. A prospective study of 26 patients. AB - To evaluate the importance of various changes during major surgery, 26 patients, electively chosen for total hip replacement (THR), were investigated for renal function preoperatively and postoperatively. In most of the patients, surgery was performed ad modum Charnley (n 25), and anesthesia was given mainly by continuous administration of bupivacaine or mepivacaine through an epidural catheter. Postoperatively, there was an improvement in glomerular filtration rate (GFR) and a reduction in renal concentrating ability (RCA), but no change in diurnal albumin excretion. No correlation was found between the change in GFR and, e.g., the degree of peroperative hypotension, bleeding, transfusions, or volume of infusions. There was a correlation between the impairment of RCA and the lowering of serum albumin concentration. In 3 patients the GFR was slightly impaired. The risk of contracting severe, acute renal failure seems low in THR performed on patients with reduced or normal kidney function. PMID- 1738977 TI - Effects of function on rat femora. AB - We evaluated the mechanical effects of different degrees of function and weight bearing on intact rat femora. Thirty rats were allocated to either an exercising, a nonweight-bearing, or a control group. The exercising rats were trained on a treadmill with a 6 weeks' running program of progressive intensity and duration. In the nonweight-bearing group, the left achilles tendon was severed at its insertion. The control rats were allowed normal activity. After 6 weeks, the animals were killed. The maximum bending moment and bending rigidity were increased in the exercised rats, whereas no differences were found between the control and nonweight-bearing rats. Bone weight and bone dimensions did not differ in the three groups. In the nonweight-bearing group, the maximum bending moment and bending rigidity were higher in the nonoperated on limb, as well as the outer and inner bone dimensions and the area moment of inertia. Our results indicate that exercise improves the mechanical characteristics of bone. PMID- 1738978 TI - Patellar complications after knee arthroplasty. A prospective study of 56 cases using the Kinematic prosthesis. AB - A prospective study on 56 knees was performed to analyze the incidence and cause of patellar complications following total knee arthroplasty with the Kinematic prosthesis inserted with the Universal Instrumentation system. Patellar complications occurred in 23 cases: 15 had anterior knee pain. There was 1 case of patellar fracture. Subluxation of the patella occurred in 13 cases, of which 6 were painful. Although the mechanical alignment was correctly reconstructed to neutral in all but 2 cases, the instrumentation tended to allow malpositioning of the components into excessive femoral valgus and compensatory excessive tibial varus that predisposed to patellar subluxation. With this prosthesis and instrumentation, patellar stability is hindered by a very short anterior femoral flange, a shallow patellar groove, and insertion of the components at 3 degrees to the mechanical axis. It should be ensured that the components are correctly positioned, that patellar stability is carefully checked before closing the capsule, and that lateral release is performed more often. PMID- 1738979 TI - Laxity and graft fixation after reconstruction of the anterior cruciate ligament. A roentgen stereophotogrammetric analysis of 11 patients. AB - The sagittal laxity of the knee was measured in 11 consecutive patients with chronic anterior cruciate ligament deficiency before and 1 year after ligament reconstruction with a free bone-tendon-bone graft from the patellar tendon (modified Clancy technique). Tantalum markers were implanted in the femur, in the tibia, and in the graft for roentgen stereophotogrammetric analysis (RSA) of the sagittal laxity and the migration of the bony ends of the graft. The precision in measurements of total anterior-posterior displacement (+/- 2 SD of the differences between repeated measurements) was 2.2 mm. A decrease in total anterior-posterior displacement from 12 mm before reconstruction of 5 mm 1 year postoperatively using a stress load of 150 N was found. The bony ends of the free graft migrated maximally 0.7 mm, implying adequate fixation. PMID- 1738980 TI - Postoperative complications of distal humeral fractures. 27/96 adults followed up for 6 (2-10) years. AB - Of 96 adult patients with a distal intercondylar, intraarticular fracture of the humerus treated operatively during a 10-year period, 27 patients suffered a local complication, while the total number of individual complications were 34. There were six postoperative infections, 12 neural injuries, and 16 fixation failures. Because of the complication, a reoperation was performed in 12 of the 27 patients. The final outcome was assessed at a reexamination after a mean follow up period of 6 (2-10) years. Three patients had a permanent dysfunction of the ulnar nerve. In another 3 patients, failure of the fixation had resulted in an established nonunion of the distal humerus. It appeared that the possibilities of internal fixation in several cases had been overestimated. PMID- 1738981 TI - Sympathetically mediated anterior knee pain. Scintigraphy and anesthetic blockade in 19 patients. AB - Nineteen patients with anterior knee pain without the classical features of reflex sympathetic dystrophy (RSD) were investigated by local anesthetic sympathetic blockade. Scintigraphy was performed before the sympathetic blockade in all the cases, and the scintigraphic appearances were correlated with the clinical response. Eleven patients responded to the blockade (9 good and 2 fair). Only 1 out of 10 patients with increased scintigraphic uptake failed to respond, whereas 7 out of 9 patients with normal uptake failed to respond. Our study suggests that a sympathetically mediated component may exist in patients with anterior knee pain without RSD, and that scintigraphy is useful in identifying those patients for whom sympathetic blockade may be helpful. PMID- 1738982 TI - A case of multifocal liposarcoma? AB - A 53-year-old man presented with a grade 2 liposarcoma in his left thigh and grade III liposarcomas in the mediastinum and omentum. Later, a grade 2 tumor was discovered in the musculature of his right thigh. In addition to recurrences, he developed lesions that were considered metastatic. He died 3 years later of multiple lesions. The case may represent a multifocal liposarcoma, which has been previously reported in only 35 cases. PMID- 1738983 TI - Blunt upper abdominal trauma: evaluation by CT. AB - CT is the technique of choice for initial examination of hemodynamically stable patients after blunt abdominal trauma. It is highly sensitive, specific, and accurate for use in detecting the presence or absence of injury and defining its extent. Nonoperative management of many posttraumatic injuries, particularly in the liver, spleen, and kidney, is possible in part because of the diagnostic usefulness of CT. CT can be used effectively to visualize the progression of liver and spleen injuries in those patients chosen for conservative management. CT helps in treatment decisions in patients with renal injury by defining the character and extent and distinguishing minor from severe renal trauma. Posttraumatic injuries to the pancrease, bowel, and mesentery can be detected with CT. In these areas, however, signs may be subtle, and a significant injury may be missed on an initial examination. PMID- 1738984 TI - Acute adrenal injury after blunt abdominal trauma: CT findings. AB - During a 32-month period, adrenal injuries were diagnosed in 20 (2%) of 1120 patients who had abdominal CT for assessment of blunt force trauma. Injuries were unilateral in 17 patients (12 right-sided and five left-sided) and bilateral in three (23 total adrenal injuries) and were accompanied by concurrent ipsilateral thoracic or abdominal injuries in all but one patient. Nineteen (83%) of the adrenal injuries appeared as discrete round to oval hematomas expanding the adrenal gland, two (9%) appeared as diffuse irregular hemorrhage obliterating the gland, and two (9%) appeared as uniform swelling of the adrenal gland. Associated CT findings included "stranding" of the periadrenal fat caused by blood in 14 cases (61%) and posterior pararenal hemorrhage mimicking a thickened diaphragmatic crus in nine cases (39%). In general, these injuries had no significant medical sequelae, but acute adrenal insufficiency developed in one patient with bilateral lesions; in another patient with an adrenal hematoma compressing the inferior vena cava, caval thrombosis developed. The potential for delayed bleeding or infection within the hemorrhagic gland exists, but these did not occur in any of our patients. Our experience indicates that adrenal injury resulting from blunt trauma is more common than suggested by previous reports and emphasizes the importance of careful inspection of the adrenal glands in patients in whom lower thoracic or upper abdominal injuries are detected by CT. PMID- 1738985 TI - Efficacy of digital radiography for the detection of pneumothorax: comparison with conventional chest radiography. AB - As part of our continuing evaluation of the clinical applicability of digital radiography, we compared the abilities of radiologists to detect pneumothoraces on conventional chest radiographs with their performances when using three formats of digitally obtained images. Twenty-three frontal-view chest radiographs with pneumothoraces and 22 other chest radiographs, either normal or showing miscellaneous abnormalities, were interpreted by five experienced radiologists in each of four formats: conventional film-screen chest radiographs, small-format (17.8 x 21.6 cm) computed radiographs, large-format (35.6 x 43.1 cm) computed radiographs, and digital images viewed on an interactive electronic workstation. The receiver-operating-characteristic curve areas for each observer for the four types of images were compared by a z test on a critical ratio, and the mean sensitivity and specificity values were compared by the sign rank test. The mean areas under the receiver-operating-characteristic curves ranged from 0.869 for the digital workstation to 0.915 for film-screen images. The differences observed among formats were not statistically significant. Mean specificities also were not significantly different, ranging from 0.90 for large-format computed radiographs to 0.96 for the digital workstation. Mean sensitivity ranged from 0.65 for the digital workstation to 0.82 for film-screen images. Radiologists interpreting digital workstation images were significantly less sensitive in detecting pneumothoraces than with film-screen and small-format computed images (p = .06). In this study, radiologists detected pneumothoraces equally well on conventional film-screen radiographs and digital images printed on film; however, they detected pneumothoraces less well on electronic viewing consoles. This latter finding reflects an important practical difference in the working behavior of radiologists interacting with a digital workstation. PMID- 1738986 TI - Bronchiolitis obliterans organizing pneumonia with migratory pulmonary infiltrates. PMID- 1738987 TI - The art of learning medicine. PMID- 1738988 TI - Pulmonary hemorrhage complicating systemic lupus erythematosus: role of MR imaging in diagnosis. PMID- 1738989 TI - Economic issues in screening mammography. AB - The issues surrounding screening mammography present apparent conflicts: conflicting guidelines for screening; an oversupply of facilities, yet inadequate access to mammography for some groups of women; increased medicolegal vulnerability as participation in screening is promoted; disparate results from studies of cost-effectiveness; wide variations in delivery modes and practice patterns of facilities, yet an evolution toward a single set price for mammography by payers for screening. This review does not claim to offer solutions to these conflicts, rather it attempts to carry forward a discussion of the issues. With these conflicts, screening mammography may be only a microcosm of similar economic issues in general health care delivery. Our health care system has room for variety, if access and quality are improved at an affordable cost. Screening for breast cancer with mammography will not reach its full potential to reduce mortality until many of these issues can be resolved. PMID- 1738990 TI - The frequency and significance of small (less than or equal to 15 mm) hepatic lesions detected by CT. AB - The purpose of our study was to determine the frequency of detection of small hepatic lesions (less than or equal to 15 mm) in outpatients who had abdominal CT and to assess the significance of these lesions in the presence or absence of known malignant tumors. Contrast-enhanced abdominal CT scans in 1454 patients were reviewed. In 254 patients (17%), hepatic lesions 15 mm or smaller were detected. In 51% of these patients, lesions were judged benign on the basis of other imaging studies, biopsy results, or stability for at least 6 months as shown by CT. Lesions were judged malignant on the basis of progression seen on radiologic studies or biopsy in 22%. The other 27% of the patients had lesions that could not be classified. The majority of patients with small hepatic lesions (82%) were known to have a malignant tumor; in 51% of these patients, lesions were diagnosed as benign. No patient without a known malignant tumor had a small hepatic lesion that was determined to be malignant. Multiple small lesions were more likely to represent malignant disease than were single small lesions. We conclude that small hepatic lesions are common (seen in 17% of our patients), and that there is a high probability that hepatic lesions smaller than 15 mm are benign, even in patients known to have an extrahepatic malignant tumor. PMID- 1738991 TI - Massive upper gastrointestinal hemorrhage with normal findings on arteriography: value of prophylactic embolization of the left gastric artery. AB - During a 5-year period, 13 patients who presented with massive upper gastrointestinal hemorrhage had normal findings on arteriography. Seven had prophylactic embolization of the left gastric artery, and six had conservative therapy. Normal angiographic findings were associated with clinical cessation of bleeding in 12 of 13 patients. Lesions not treated by embolization or other invasive therapy had a high rate of massive recurrent hemorrhage (four of six). Of lesions subsequently found to be supplied by the left gastric artery, two of four cases not treated by embolization or surgery had clinically significant recurrent hemorrhage, whereas none of six cases treated by embolization had recurrent hemorrhage. Prophylactic embolization of the left gastric artery appears warranted when (1) there is definite prior identification of a lesion in the left gastric artery territory or (2) there is no prior localization of a lesion but the patient is at risk for multiorgan failure if bleeding recurs. PMID- 1738992 TI - Hemorrhagic colitis caused by Escherichia coli preceding hemolytic-uremic syndrome: radiologic features. PMID- 1738993 TI - Diagnosis of primary hyperaldosteronism: importance of correlating CT findings with endocrinologic studies. AB - Twenty patients with primary hyperaldosteronism had endocrinologic and radiologic studies to distinguish aldosterone-producing adenoma from idiopathic hyperaldosteronism due to bilateral micro- or macronodular hyperplasia of the adrenal cortex. In addition to examination for changes in the plasma level of aldosterone associated with postural changes and measurement of the plasma level of 18-hydroxycorticosterone, all 20 patients had CT examination of the adrenal glands. In three patients with normal adrenal glands on CT and three patients with CT evidence of two solitary nodules, one in each adrenal gland, a diagnosis of idiopathic hyperaldosteronism was confirmed by endocrinologic findings (five patients) or 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy (one patient). In nine patients with a solitary adrenal nodule on CT, a diagnosis of aldosterone-producing adenoma was confirmed by surgery (seven patients) or hormone sampling via the adrenal veins (two patients). However, in three patients with a solitary adrenal nodule on CT, a diagnosis of idiopathic hyperaldosteronism was suggested by endocrinologic findings (three patients) and confirmed by the results of NP-59 scintigraphy (two patients) or adrenal venous sampling (one patient). In addition, in two patients with CT evidence of three adrenal nodules (two in one gland, one in contralateral gland), a diagnosis of aldosterone-producing adenoma was suggested by endocrinologic findings in both patients and confirmed by surgery in one. Although high-resolution CT is highly accurate for the detection of aldosterone-producing adenoma, significant diagnostic errors can occur in patients with primary hyperaldosteronism if CT findings are not correlated with results of endocrinologic studies. PMID- 1738994 TI - MR imaging in adenocarcinoma of the prostate: interobserver variation and efficacy for determining stage C disease. AB - Patients with adenocarcinoma of the prostate confined to the gland (stage B) are candidates for a potentially curative surgical procedure (radical retropubic prostatectomy). However, patients with adenocarcinoma that penetrates the capsule or invades the seminal vesicles (stage C) are no longer considered good candidates for surgical cure of their disease. The purpose of this study was to compare the ability of four radiologists to detect stage C disease on MR images and to evaluate interobserver variability. One hundred consecutive MR studies of the prostate were reviewed independently by four radiologists to determine whether the cancer was stage C (capsule penetration or seminal vesicle invasion by tumor). A radical prostatectomy was performed in each case, and careful histologic assessment was made of the prostatic capsule and seminal vesicles for any evidence of stage C disease. The sensitivity, specificity, and accuracy (true positive + true-negative/100 patients) in detecting stage C disease were calculated for each of the four readers. Four receiver-operating-characteristic curves were generated and compared by means of the univariate z score. Percentage agreement was calculated for five specific areas of the prostate on MR images, and observations made by the best reader were compared with the other three to help determine interreader variability. The results showed that the sensitivity and specificity of MR imaging in detecting stage C disease ranged from .24 to .61 (mean, .48) and .49 to .79 (mean, .66), respectively. The accuracy of MR imaging ranged from .47 to .61 (mean, .55). The univariate z score test showed that one of the readers significantly differed from the other three. The average percentage agreement between that reader and the other three was 70% for the five separate anatomic regions. This study shows that considerable interobserver variation exists in the interpretation of MR images for staging cancer of the prostate. The average accuracy among four radiologists in determining the presence of stage C adenocarcinoma of the prostate from MR images was only slightly above a chance guess at .55. PMID- 1738995 TI - Myometrial invasion by endometrial carcinoma: assessment by MR imaging. AB - In patients with early-stage endometrial cancer, preoperative knowledge of myometrial tumor extension has important prognostic and therapeutic implications. The purpose of this prospective study was to determine the sensitivity and specificity of MR imaging for assessing the depth of myometrial invasion in patients with endometrial cancer that clinically was thought to be confined to the uterine corpus. Sixty-five consecutive patients were included in the study. All patients had MR imaging before radical surgery. MR imaging findings were compared with microscopic pathologic findings in all cases. On MR images and at histologic analysis, myometrial invasion was classified as absent (tumor confined to the endometrium), superficial (less than 50% of myometrial thickness), or deep (50% or more of myometrial thickness). At histologic examination, tumor limited to the endometrium was proved in 14 cases, superficial myometrial invasion by tumor was present in 34 cases, and deep tumor invasion was demonstrated in 17 cases. In determining the presence of tumor confined to the endometrium, MR imaging had a sensitivity of 57% and a specificity of 96%. In the assessment of tumor with superficial myometrial invasion, MR imaging had a sensitivity and a specificity of 74%, whereas in assessing deep myometrial penetration, the sensitivity and specificity of MR were 88% and 85%, respectively. Errors in MR interpretation when determining myometrial tumor spread were more frequently overestimations rather than underestimations. Our results indicate that MR imaging is useful for the preoperative assessment of myometrial invasion in patients with proved endometrial cancer. PMID- 1738996 TI - Renal lymphoma. PMID- 1738997 TI - Renal tuberculosis: diagnosis with sonographically guided aspiration cytology. AB - Sonographically guided fine-needle aspiration cytology was performed in 19 patients suspected to have renal tuberculosis. This procedure enabled a diagnosis of renal tuberculosis to be made in six of seven patients with urine cultures consistently negative for acid-fast bacilli and confirmed the diagnosis in nine patients with focal renal lesions on sonography and urine cultures positive for acid-fast bacilli. The fine-needle aspiration cytologic samples were positive for acid-fast bacilli in seven (44%) of the 16 confirmed cases, and acid-fast bacilli were present in 80% of the samples containing necrotic material. Epithelioid granulomas were present in 15 (94%) of 16 patients diagnosed with renal tuberculosis. One patient had no evidence of acid-fast bacilli or epithelioid granulomas, but seminal fluid ultimately grew acid-fast bacilli. Two patients (13%) with evidence of tuberculosis had minor self-limiting complications from the fine-needle aspiration: one perirenal hematoma and one abdominal wall intramuscular hematoma. Sonographically guided fine-needle aspiration cytology is useful as a means of diagnosing renal tuberculosis in patients with urine cultures negative for acid-fast bacilli, and is of value in defining the granulomatous nature of sonographically visible lesions in patients with positive urine cultures. PMID- 1738998 TI - CT findings in tuboovarian abscess. AB - Pelvic inflammatory disease with tuboovarian abscess can cause a wide range of radiologic abnormalities. Although the diagnosis of tuboovarian abscess is usually straightforward and is based on clinical and sonographic findings, unusual or unsuspected cases may be confused with other pelvic or abdominal diseases. The purpose of this essay is to illustrate the CT findings in tuboovarian abscess. PMID- 1738999 TI - MR imaging of extraabdominal desmoids: differentiation from other neoplasms. AB - A retrospective review of MR images of 36 patients with histologically proved extraabdominal desmoids was done to define the MR characteristics of these tumors and to determine if MR could be used to differentiate desmoids from other benign and malignant soft-tissue neoplasms. The desmoids evaluated included eight primary and 30 recurrent lesions. Our study was conducted in parallel with another study in which the MR appearance of 95 benign and malignant soft-tissue masses was evaluated, and the MR images of these masses were compared with our findings. The four desmoids from that study are included in our data. The signal intensity of the tumor on T1- and T2-weighted images was graded relative to the intensities of muscle and fat. Homogeneity, margin, neurovascular and bone involvement, and fibrosis (low-signal regions within the tumor on both T1- and T2 weighted images) were evaluated. On MR imaging, the desmoids showed inhomogeneous signal (97%), poor margination (89%), neurovascular involvement (58%), and bone involvement (37%). Fibrosis was present in 88% of primary desmoids and 90% of recurrent ones, and intermediate signal (greater than that of muscle and less than that of fat) was present in 75% and 50% of these, respectively. Our results show that the MR features of desmoids have characteristics that are commonly found in malignant tumors (inhomogeneous signal, poor margination, and neurovascular involvement). MR features of desmoids that distinguish them from malignant neoplasms are the presence of fibrosis and intermediate signal in the regions of the tumor. PMID- 1739000 TI - MR diagnosis of meniscal tears of the knee: value of axial three-dimensional Fourier transformation GRASS images. AB - Axial MR images of 40 knees in 37 patients with clinically suspected meniscal tears were obtained by using a three-dimensional (3-D) Fourier transform, gradient-refocused acquisition in the steady state (GRASS) pulse sequence. All knees also were examined in both coronal and sagittal planes with a two dimensional (2-D) Fourier transform, spin-echo pulse sequence for T1-weighted images and a multiplanar GRASS pulse sequence for T2*-weighted images (conventional 2-D pulse sequences). Arthroscopic confirmation was available in all cases and was used as the gold standard. In these 40 knees, 32 of 33 meniscal tears and 45 of 47 normal menisci were correctly identified with axial 3-D imaging, yielding a sensitivity of 97% and specificity of 96%. Conversely, the sensitivity was 82% and the specificity was 100% for the 2-D technique in the diagnosis of meniscal tears. A combination of both techniques yielded 100% sensitivity, 100% specificity, and 100% accuracy in the evaluation of the menisci. Seven discrepancies between the findings of the two techniques were found in the evaluation of 33 arthroscopically proved torn menisci; six of the seven represented false-negative 2-D images and one was a false-negative axial 3 D image. Of 47 normal menisci, only two false-positives occurred with axial 3-D imaging and none with 2-D imaging. Despite the lack of a statistically significant difference, these preliminary findings suggest that the sensitivity in the diagnosis of meniscal tears can be improved by adding thin-sliced axial images with the 3-D GRASS pulse sequence to conventional 2-D imaging. PMID- 1739001 TI - CT and MR evaluation of the labral capsular ligamentous complex of the shoulder. AB - Stability of the glenohumeral articulation is dependent on the integrity of the rotator cuff, labrum, glenohumeral ligaments, capsular elements, and bony glenoid. The importance of the soft-tissue elements in maintaining stability has been well documented in the surgical literature but has only recently been introduced into the radiologic literature. The purpose of this essay is to illustrate the normal labrum, capsular complex, and glenohumeral ligaments, including common congenital variations as depicted by CT arthrography and MR imaging, and to describe the pathologic findings leading to shoulder instability. PMID- 1739002 TI - Radiation-induced insufficiency fractures of the pelvis: evaluation with 99mTc methylene diphosphonate scintigraphy. AB - 99mTc-methylene diphosphonate (99mTc-MDP) bone scans in 80 patients, 30-80 years old (average, 62 years old) with uterine cancer who received high doses of radiation (10-60 Gy; average, 46 Gy) were reviewed retrospectively to evaluate the frequency of pelvic insufficiency fractures caused by radiotherapy and to study the appearance of the fractures on bone scans. Bone scans in 29 of 80 patients showed abnormalities in the pelvis: insufficiency fractures were identified in 27 patients (34%) and osseous metastases were found in two patients (3%). The fractures and metastases were diagnosed by CT and were confirmed by observing the patients' clinical courses. Fractures were identified in 27 (39%) of 69 postmenopausal women and in none of 11 premenopausal patients (p greater than .05). Fractures were found in 21 (84%) of 25 patients who had pelvic pain and in six (11%) of 55 patients who were asymptomatic (p greater than .001). Scintigrams in patients with fractures showed more than one fracture in most patients (85%), and fractures were often symmetric (67%). Scintigrams in two patients with osseous metastases showed increased activity in an iliac wing that was outside the radiation field. Our results suggest that a marked increase in insufficiency fractures occurs after radiation therapy, especially in postmenopausal patients. A symmetric area of increased uptake of radionuclide is a characteristic scintigraphic appearance of an insufficiency fracture. PMID- 1739003 TI - Musculoskeletal infections in patients with AIDS: CT findings. AB - The CT appearances of various musculoskeletal infections found in patients with AIDS are illustrated. Recognition of these infections is important for management of patients, but conventional laboratory tests may be inadequate in screening for infection or confirming the response of the host to therapy. As a screening examination for patients with AIDS, CT can suggest or confirm the presence of musculoskeletal infections even when infection has not been suspected. PMID- 1739004 TI - An unusual epiphyseal osteoid osteoma. PMID- 1739005 TI - The normal and abnormal scrotum in children: evaluation with color Doppler sonography. AB - The use of color Doppler sonography to evaluate the symptomatic testes in children with scrotal pain or swelling was prospectively studied with a fourth generation color sonographic unit with a 7-MHz linear transducer. The 32 patients were 1 day to 18 years old (mean age, 8.6 years). Results were correlated with scintigraphic findings in 23 patients, with the final diagnosis established by surgery in 12 patients, and with clinical follow-up in all patients. Eight cases of testicular torsion, including two of acute torsion and six of late torsion, were correctly detected by color Doppler sonography and confirmed surgically. In the remaining patients, perfusion of the testis was correctly detected by color Doppler examination. The final diagnoses in these patients included torsion of the appendix testis (15 patients), epididymitis (five patients), epididymo orchitis (one patient), yolk sac tumor of the testis (one patient), hydrocele (one patient), and local reaction to an insect bite (one patient). The ability to detect blood flow in the normal contralateral testis was also evaluated in 28 patients. Blood flow was demonstrated in normal testes larger than 1 cm3. Detection of flow in the very small normal prepubertal testis was often difficult, and no flow was identified in one testis. Flow was identified in central arteries in only six of 13 testes smaller than 1 cm3. We conclude that color Doppler sonography is helpful in the initial evaluation of pediatric testes, providing accurate evaluation of the involved hemi-scrotum in our patients and also providing the benefit of both structural and flow information. Until our sensitivity to low-velocity flow improves, we would not suggest the exclusive use of color Doppler sonography in the evaluation of testicular perfusion in the prepubertal patient. We advocate the addition of testicular scintigraphy to corroborate the presence of testicular perfusion when flow in intratesticular arteries cannot be established with certainty by color Doppler sonography. PMID- 1739006 TI - Plain film diagnosis of intussusception: prevalence of the target sign. AB - We describe a feature of intussusception seen on plain abdominal films that to our knowledge has not been previously described. The abnormality, termed the "target sign," consists of two concentric, circular, radiolucent lines to the right of the spine superimposed on the kidney. Four observers examined 280 plain abdominal films; 180 were of 94 patients who had had 100 episodes of intussusception and 100 films were of 80 control subjects. The target sign was observed by three or four observers on plain films in 24 (26%) of 94 patients with intussusception and on 4% of radiographs of control subjects. There was no concordance between observers on false-positive findings seen in the control subjects. Our experience suggests that circular radiolucent lines superimposed on the right kidney on plain abdominal radiographs (target sign) constitute a useful diagnostic feature of intussusception. PMID- 1739007 TI - Thoracic outlet syndrome: evaluation of the subclavian vessels by color duplex sonography. AB - Changes in flow in the subclavian artery and vein resulting from the use of a hyperabduction maneuver during Doppler sonography in 20 volunteers were compared with retrospective findings in 16 patients clinically suspected of having thoracic outlet syndrome. Significant compression of the subclavian artery showed in the Doppler waveform as at least a doubling of peak systolic velocity or complete cessation of flow with hyperabduction; significant compression of the subclavian vein was diagnosed by complete cessation of blood flow or loss of atrial and respiratory dynamics in the waveform of the subclavian vein with hyperabduction. In volunteers, asymptomatic compression of the subclavian vein with arm abduction was seen in two (10%) and asymptomatic compression of the subclavian artery was seen in four (20%). Of the 16 patients, thrombosis of the subclavian vein was found in seven, compression of the subclavian vein with hyperabduction was found in six, and diagnoses other than thoracic outlet syndrome were established as the cause of pain in three. When duplex sonography was compared with venography, which was performed in 10 patients, one false negative case was found because a subclavian vein thrombus had not been detected. The subclavian artery was examined in five of the six patients with positional compression of the subclavian vein; compression of the subclavian artery was found in three. The clinical significance of compression of the subclavian artery cannot be determined from our data because of the small number of patients involved. When the sonographic criteria of subclavian vein clot or compression resulting in a complete loss of normal venous phasicity with arm abduction and the clinical criterion of subsequent improvement in symptoms after curative surgery are used, color Doppler sonography is 92% sensitive and 95% specific for the diagnosis of thoracic outlet syndrome. This preliminary study shows that Doppler sonography has potential in the evaluation of thoracic outlet syndrome. PMID- 1739008 TI - Arterial injury from penetrating trauma: evaluation with single-acquisition fat suppressed MR imaging. PMID- 1739009 TI - Combined saccular aneurysm and proximal interruption of the inferior vena cava associated with Budd-Chiari syndrome. PMID- 1739010 TI - Catheter-induced pulmonary artery pseudoaneurysm: the halo sign on CT. PMID- 1739011 TI - Temno biopsy needle: evaluation of efficacy and safety in 165 biopsy procedures. PMID- 1739012 TI - Detection of residual or recurrent meningioma after surgery: value of enhanced vs unenhanced MR imaging. AB - The enhanced and unenhanced MR examinations obtained after surgery for meningioma in 38 patients were reviewed to determine the value of enhanced vs unenhanced MR imaging for the detection of residual or recurrent tumor. Enhanced images improved delineation of the extent of tumor in seven of 13 cases in which meningioma was identified on unenhanced images and allowed more definitive detection or exclusion of residual or recurrent meningioma in 18 of 21 cases with equivocal findings on unenhanced images. In addition, enhanced images were helpful for detecting small recurrences, identifying en plaque growth, and showing subtle progression on serial studies. Enhanced MR imaging also allowed detection of two morphologic patterns of dural enhancement adjacent to the surgical bed: (1) thin and smooth, which was seen in patients both with and without residual or recurrent tumor, and (2) thick and nodular, which was seen only in patients with findings indicative of, or at least suggestive of, residual or recurrent meningioma. Unenhanced images failed to detect, or poorly detected, these dural abnormalities. Unenhanced sequences were necessary for accurate interpretation of the enhanced images (e.g., identification or exclusion of hemorrhage). The combination of unenhanced and enhanced MR imaging is recommended for the detection of residual or recurrent meningioma after surgery. PMID- 1739013 TI - Sequence of enhancement of various portions of the pituitary gland on gadolinium enhanced MR images: correlation with regional blood supply. AB - In an effort to study the blood supply of the pituitary gland, we determined the sequence in which various portions of the gland enhanced on MR images obtained after administration of gadopentetate dimeglumine in seven healthy volunteers. The pituitary gland has a unique blood supply: the pars nervosa is supplied by the inferior hypophyseal arteries; the infundibular stem is supplied by the superior hypophyseal arteries, which are more distal than the inferior hypophyseal arteries; and the pars distalis is supplied indirectly by portal systems from the infundibular stem. Therefore, the expected sequence of contrast enhancement of the pituitary gland is: the pars nervosa first, the infundibular stem second, and the pars distalis last. However, it is difficult to evaluate the temporal sequence of contrast enhancement with "slow" conventional MR techniques, such as routine enhanced images acquired minutes after contrast administration. Accordingly, we used rapid enhanced gradient-echo sequences (14 sec/image) and the region-of-interest method to determine contrast enhancement for various portions of the gland. Enhancement-time curves were then plotted for each portion and compared to determine the sequence of enhancement. Our results show that the timing of contrast enhancement of various parts of the pituitary gland as demonstrated on MR imaging correlates closely with the expected perfusion sequence based on knowledge of regional vascular anatomy. Normal enhancement-time curves of different portions of the pituitary gland were established. This technique and baseline data can be used to evaluate patients with hypopituitarism caused by ischemia. PMID- 1739014 TI - MR imaging of the stellate ganglion: normal appearance. AB - The stellate ganglion has not previously been identified by imaging techniques. MR imaging shows the stellate ganglion at the thoracic inlet adjacent to the neck of the first rib, lateral to the longus colli muscle and posterior to the vertebral artery. Although its shape varies somewhat, it can be identified consistently in normal persons. PMID- 1739015 TI - MR appearance of osteogenic sarcoma of the calvaria. PMID- 1739016 TI - Monitoring heart rate and oxygen saturation with a fiber-optic pulse oximeter during MR imaging. PMID- 1739017 TI - Comparison of iohexol 300 and diatrizoate meglumine 60 for body CT: image quality, adverse reactions, and aborted/repeated examinations. AB - Six hundred patients were prospectively randomized and given either diatrizoate meglumine 60 or iohexol 300 during dynamic contrast-enhanced body CT in order to compare image quality, contrast reactions, and the number of aborted studies or studies in which images had to be repeated. Three hundred two patients received iohexol 300, and 298 patients received diatrizoate meglumine 60. Thirty-nine percent (119/302) of the patients given iohexol 300 and 63% (188/298) of the patients given diatrizoate meglumine 60 had at least one adverse reaction thought to be related to contrast material during, or within 24 hr of, the body CT scan. When reactions of discomfort (heat or warmth, flushing, bad taste) were excluded, 16% (48/302) of the patients who received iohexol and 33% (99/298) of the patients who were given diatrizoate meglumine 60 had at least one adverse reaction. The differences in both types of reactions between the two agents were significant (p less than .001). Among scans evaluated for study quality, 71% (214/302) of the iohexol 300 group and 62% (184/298) of the diatrizoate meglumine 60 group had optimal enhancement (p = .02). However, when the optimal and adequate categories were combined, 301 of 302 patients given iohexol 300 and 292 of 298 patients given diatrizoate meglumine 60 had diagnostic-quality studies (no statistical difference). Studies were not terminated nor were images repeated in 97% (292/302) of the patients given iohexol 300 and in 94% (280/298) of those given diatrizoate meglumine 60. The CT study was repeated because of movement during the contrast injection or aborted because of contrast-related reactions in 0.7% of the patients given iohexol 300 and in 3.0% of the patients given diatrizoate meglumine 60. This difference was statistically significant (p = .04). Our results suggest that the difference in image quality, number of adverse reactions, and number of aborted/repeated CT scans performed with iohexol 300 or diatrizoate meglumine 60 are not sufficiently different to warrant conversion to nonionic agents for body CT scans. PMID- 1739018 TI - Hypercard coding system for the ACR Index for Radiological Diagnoses. AB - We describe a computer version of the Index for Radiological Diagnoses of the American College of Radiology (ACR). This system combines a graphics interface with a search mechanism while preserving the hierarchical structure of the Index. The graphics interface allows easy selection of an anatomic part, while the search mechanism provides the code numbers associated with an entered term. The computer system and the paperback version of the ACR Index were compared by having 52 volunteers (21 radiology faculty members, 21 radiology residents, and 10 medical students) each code 30 cases with the book and a matched set of 30 cases with the computer. The average time to code cases was shorter when the computer was used (52.2 vs 64.5 sec; p less than .0001). Accuracy was higher when the computer was used (96.4% vs 90.4%; p less than .0001). The average confidence in the computer diagnosis was also higher (9.73 vs 9.51, on a scale of 1-10; p = .0016). This system demonstrates the ability of a computer program to outperform an analogous noncomputerized system. PMID- 1739019 TI - Radiologic application of a microcomputer-based three-dimensional imaging system. PMID- 1739020 TI - Radiology summit meeting--1991: Solutions through synectics. PMID- 1739021 TI - Western Neuroradiological Society, 23rd annual meeting: October 1991. PMID- 1739022 TI - Ruptured pulmonary hydatid cyst and folded membrane on CT. PMID- 1739023 TI - Pneumopyopericardium after penetrating chest injury. PMID- 1739024 TI - Positive predictive values for mammographically detected carcinomas. PMID- 1739025 TI - Mammographic appearance of coumadin-induced fat necrosis. PMID- 1739026 TI - Latex retention balloon for barium enemas. PMID- 1739027 TI - Visceral calcifications in AIDS. PMID- 1739028 TI - Ewing sarcoma manifested as acute abdomen. PMID- 1739029 TI - Sonography vs MR imaging in children who are candidates for liver transplantation. PMID- 1739030 TI - The looking-down view for pelvic MR imaging. PMID- 1739031 TI - Leiomyoma of the urethra: appearance on transvaginal sonography. PMID- 1739032 TI - Accessory occipital ventricle. PMID- 1739033 TI - Insomnia in the elderly. PMID- 1739034 TI - The term 'egg' and contraception. PMID- 1739035 TI - Nicardipine-induced hyperglycemia. PMID- 1739036 TI - Cracking down on 'neck cracking'. PMID- 1739037 TI - CPT coding changes: another progeny of Medicare reimbursement. PMID- 1739038 TI - Update on breast implants. PMID- 1739039 TI - Competency and the routine discussion of advance directives. PMID- 1739040 TI - Medicare hassles and family physicians. PMID- 1739041 TI - Diary from a week in practice. PMID- 1739042 TI - Osteoarthritis. AB - Osteoarthritis is a frequent cause of physical impairment in the elderly. The disease has a slow, progressive course that ends with joint failure and subsequent disability. The hands and the large weight-bearing joints are most commonly affected. The cause of osteoarthritis is unknown. The strongest risk factor is age, but age alone does not cause the disease. Clinically, osteoarthritis is manifested by joint pain and stiffness. Radiographs reveal joint space narrowing, subchondral sclerosis, osteophytes and, later, subchondral cysts and intra-articular osseous bodies. Biochemically, the cartilage in osteoarthritis differs from normal cartilage in elderly patients. The goals of treatment are to control pain, maintain function through strengthening and range of-motion exercises, protect the joint and limit iatrogenic injury by selecting treatment options that minimize complications. Even when cure is not possible, appropriate medical care can improve the patient's functioning and well-being. PMID- 1739043 TI - Infection of fetal scalp electrode monitoring sites. AB - Complications caused by placement of a fetal scalp electrode include trauma, hemorrhage and infection. Infections are usually localized and self-limited, but they can occasionally lead to serious complications, such as osteomyelitis, sepsis and death. The recommended treatment for a scalp abscess is incision and drainage, followed by appropriate antibiotic therapy. If a serious infection is suspected, the infant should be hospitalized, blood cultures obtained and intravenous antibiotic therapy initiated. PMID- 1739044 TI - Occupational repetitive strain injury. AB - Repetitive strain injuries include a group of disorders that most commonly develop in workers using excessive and repetitious motions of the neck and upper extremity. A careful occupational history, physical examination and specific diagnostic maneuvers can help distinguish these musculoskeletal injuries from rheumatologic diseases, psychologic disorders, acute joint or tendon inflammation from other causes and single-event traumatic sprains and strains. Repetitive strain injury may be manifested by cervical syndrome, tension neck syndrome, thoracic outlet syndrome and frozen shoulder syndrome. Common injuries involving the elbow, wrist and hand include epicondylitis, carpal tunnel syndrome and ulnar nerve entrapment. Conservative treatment consisting of rest, application of ice or heat and anti-inflammatory drugs is usually effective, but the injury may take weeks or months to resolve. Modifications in the workplace can prevent many of these injuries and may be required to prevent reinjury after the patient returns to work. PMID- 1739045 TI - An approach to nutrition screening for older Americans. AB - The Nutrition Screening Initiative suggests an adaptable, tiered approach to screening for poor nutritional status in older Americans. The first level of screening is a checklist to be completed by elderly individuals or their caregivers. This checklist, which will be widely disseminated, describes the warning signs of poor nutritional status. It is anticipated that individuals will approach their physicians on the basis of scores on this checklist. Also included are two screening tests designed to help clinicians more easily detect poor nutritional status, or risk factors for poor nutrition, in their patients. The level I screen is to be completed by a social service or health care professional, or by other trained personnel. The level II screen focuses on additional information to be obtained following referral to a physician or other qualified health care professional. PMID- 1739046 TI - Acute rheumatic fever: an update. AB - The incidence of acute rheumatic fever is increasing in the United States, but many physicians are now unfamiliar with the diagnosis and treatment of this disease. The revised Jones criteria provide guidance for the diagnosis of rheumatic fever; two major criteria or one major and two minor manifestations are required to make the diagnosis. Salicylates are usually the initial treatment of choice for the arthritis of rheumatic fever. Penicillin remains the recommended prophylactic agent for secondary prevention. PMID- 1739047 TI - Recognizing an index case of type 1 neurofibromatosis. AB - Neurofibromatosis is a relatively common autosomal dominant disorder with variable penetrance. The disorder usually presents in childhood. Hallmarks of type 1 neurofibromatosis are cafe-au-lait macules and neurofibromas. Neurologic complications include mental retardation, learning disabilities and seizures. Tumors of the eighth cranial nerve, as well as other intracranial and spinal neoplasms, are the typical lesions in type 2 neurofibromatosis. Both forms of neurofibromatosis have a highly variable course and may result in progressive neurologic deterioration, disfigurement and impingement syndromes. In the 50 percent of cases that represent new mutations, diagnosis may be delayed if the physician is not familiar with the salient features of the disorder. Thorough initial evaluation, genetic counseling and close follow-up are important aspects of management. PMID- 1739048 TI - Klippel-Feil syndrome. AB - The triad of short neck, low posterior hairline and severe restriction of cervical motion is a classic definition of Klippel-Feil syndrome. The anatomic and clinical expressions of this syndrome vary widely, ranging from mild cosmetic deformity to severe disability. The diagnosis is usually apparent on lateral cervical radiographs. PMID- 1739049 TI - Thrombolytic therapy in acute myocardial infarction. AB - Multiple clinical trials have demonstrated that thrombolytic treatment early in the course of acute myocardial infarction significantly reduces mortality. Patients under 75 years of age who have had chest pain for no longer than six hours and who demonstrate ST-segment elevation on electrocardiogram are the best candidates for this therapy. Recent studies suggest that there is little difference in effectiveness among streptokinase, alteplase and anistreplase. However, streptokinase is 10 times less expensive than the other agents and causes fewer intracranial bleeds, the major serious adverse effect of thrombolytic therapy. An advantage of anistreplase is that it can be given in a five-minute bolus injection, compared with a one-hour infusion for streptokinase and a three-hour infusion for alteplase. Thrombolytic therapy is contraindicated in patients with known pregnancy, active internal bleeding, uncontrolled hypertension, aortic dissection, intracranial neoplasm or a history of hemorrhagic stroke. Heparin should be administered with both alteplase and streptokinase. Aspirin, beta blockers, nitrates and lidocaine are useful adjunctive therapies in the setting of an acute myocardial infarction. PMID- 1739050 TI - Contrast sensitivity vision testing: new screening technology for family physicians. AB - Contrast sensitivity vision testing is the new technology in visual screening. Easy to administer and quick to perform, contrast sensitivity vision testing appears to be cost-effective for use by family physicians. It is a more sensitive indicator of ocular disease than traditional Snellen acuity testing and may detect ocular pathology at an early stage when Snellen acuity is still normal. PMID- 1739051 TI - Foreign-body granuloma due to an unsuspected wooden thorn. AB - Foreign bodies occasionally cause a chronic granulomatous reaction that may be mistaken for a plantar wart or even a skin malignancy. This possibility should be considered when lesions on the foot become progressively larger and more tender. Diagnosis may require surgical excision. PMID- 1739052 TI - Exercise stress testing for the family physician: Part II. Interpretation of the results. AB - Information gained from exercise stress testing includes the heart rate and blood pressure response, the presence of symptoms or dysrhythmias, functional aerobic capacity and evidence of myocardial ischemia. Certain ST-segment patterns correlate with various degrees of ischemia. Overall, stress testing has a sensitivity and a specificity of about 70 and 75 percent, respectively, but the results are even more useful than this when considered in light of the pre- and post-test probability of coronary artery disease. Use of the exercise test score and decision-tree algorithms is helpful in clinical decision making. PMID- 1739053 TI - Treatment of exacerbations of COPD. AB - Chronic obstructive pulmonary disease (COPD) affects approximately 14 million Americans. Treatment of COPD includes bronchodilators, corticosteroids and antibiotics. The most common bacterial isolates during exacerbations of COPD are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. PMID- 1739054 TI - A guide to the new office evaluation and management codes for 1992. AB - The new office evaluation and management codes require an understanding of definitions that have been recently created by the Current Procedural Terminology (CPT) Editorial Panel. Code selection is based on seven components; the three key components are the history, the physical examination and medical decision making. Office visit codes are divided into five levels of visits, based on service. New patient office visits require all three key components for any level visit; established-patient office visits require only two of the three components. The new office code descriptions were created to assist physicians in code selections. Only when counseling or coordination of care dominates the visit (e.g., more than 50 percent) is time to be considered a controlling factor. Physicians are urged not to code only from time descriptors. The 1992 CPT book will list only the new evaluation and management codes, deleting the old level-of service codes. Physicians are encouraged to contact local insurance carriers to ensure that they will also be using the new codes in 1992. PMID- 1739055 TI - Cosmetic breast surgery. AB - Appropriate follow-up care, including early postoperative serial mammography, is essential for women receiving cosmetic breast surgery. Common procedures include augmentation or reduction mammoplasty and breast reconstruction following mastectomy for cancer. Postoperative complications include infection, poor wound healing and pain. Hypertrophic scar formation, which may disrupt the normal breast contour, may be reduced by gentle and frequent massage of the scar. Avoiding sun exposure and using sun screens may prevent hyperpigmentation of the scar. Reduction mammoplasty is associated with sensory loss, which is occasionally permanent. Special complications associated with augmentation mammoplasty include diffusion of silicone through the implant and unfavorable breast appearance secondary to capsular contracture. Capsular contracture may be prevented by regular implant exercises. Preoperative and early postoperative serial mammograms are essential to differentiate surgical from malignant changes. PMID- 1739056 TI - Practical approach to the treatment of hypothyroidism. AB - Hypothyroidism most commonly is the result of primary thyroid failure due to autoimmune thyroiditis, but also may follow treated Graves' disease or may occur as transient hypothyroidism. Laboratory evaluation of thyroid function has been refined by the development of ultrasensitive thyroid-stimulating hormone determinations, allowing accurate diagnosis of primary hypothyroidism and assessment of treatment response. Determining whether therapy is appropriate for patients with subclinical hypothyroidism or euthyroid sick syndrome requires clinical judgment in addition to laboratory evaluation. Thyroid hormone replacement for hypothyroidism is best accomplished with levothyroxine. Factors that may affect serum thyroxine levels include thyroid binding globulin levels, drug interactions and variations in thyroxine absorption and clearance. PMID- 1739057 TI - Hydrocephalus in infancy and childhood. AB - Hydrocephalus is marked by the excessive accumulation of cerebrospinal fluid within the ventricles. The disorder is characterized by an imbalance in the production and reabsorption of cerebrospinal fluid. Congenital hydrocephalus is usually the result of an intrauterine infection or maldevelopment of the aqueduct of Sylvius. Acquired hydrocephalus can be caused by infection, neoplasm or hemorrhage. In infants, hydrocephalus usually presents as progressive head enlargement. The presenting symptoms in children are irritability, headache, nausea, vomiting and lethargy. Diagnosis is made with ultrasonography, computed tomography or magnetic resonance imaging. The majority of patients are treated with cerebrospinal fluid shunt procedures, most commonly the placement of ventriculoperitoneal or lumboperitoneal shunts. The outcome of hydrocephalus is determined by the etiology, the presence or absence of associated anomalies, and the timeliness of diagnosis and treatment. PMID- 1739058 TI - Assessing patient competence for medical decision making. AB - Competence frequently becomes an issue when a patient refuses a recommended surgical procedure or medication, refuses a placement option such as a nursing home or threatens to leave the hospital against medical advice. Physicians often struggle to balance the patient's right to self-determination and informed consent with their own mission to provide patients with optimal treatment. At present, few guidelines exist to assist physicians in making competence determinations. Legal precedents and conceptual issues in evaluating competence are reviewed. A protocol for assessing competence is presented. PMID- 1739059 TI - Alternatives to physical and pharmacologic restraints in long-term care. AB - The most effective programs for reducing the use of restraints involve facility policy initiatives that are strongly supported by the medical director, the administrator and the director of nursing. The physician and nursing home staff must recognize that physical and pharmacologic restraints have different purposes. Implementing alternatives to restraints requires a careful examination of the source of the problem behavior and an individualized approach. Alternatives to medication should be stressed. When a medication is necessary, it should be prescribed for a limited time, with a definite date for discontinuation. Family physicians can actively participate in restraint reduction programs, whether by initiating the process or by providing support and counseling to staff. PMID- 1739060 TI - Orofacial pain: diagnosis and treatment. AB - Orofacial pain can have an inflammatory, neurologic or musculoskeletal cause. Inflammatory diseases include dental abscess, sinusitis, temporal arteritis, sialolithiasis and infections of the parotid gland. Common neurologic diseases that cause facial pain are trigeminal neuralgia, glossopharyngeal neuralgia, paratrigeminal neuralgia and cluster headaches. Musculoskeletal causes include temporomandibular joint syndrome and myofascial pain dysfunction syndrome. A clear understanding of pertinent anatomy and an organized approach to diagnosis will facilitate the evaluation of patients with orofacial pain. PMID- 1739061 TI - Treatment of accidental hypothermia. AB - Hypothermia is an underreported cause of death in the United States. The clinical presentation of hypothermia may include neurologic, cardiovascular and metabolic abnormalities. In severely hypothermic patients, evaluation may reveal no signs of life until the patient is rewarmed. Treatment is directed at restoring normal body temperature and attending to fluid resuscitation, electrolyte disorders, cardiac arrhythmias and associated disease states or conditions. Groups at particular risk for hypothermia include outdoor workers, the homeless, trauma victims and the very young or very old. Also at risk are persons with preexisting serious illnesses and those who are taking medications or abusing drugs. Cardiac arrest, hypotension, unresponsiveness and severe hyperkalemia portend a poorer prognosis. PMID- 1739062 TI - Clozapine: a novel antipsychotic. AB - Clozapine is the first truly new antipsychotic drug introduced in the last 40 years. Compared to traditional neuroleptic agents, clozapine appears to have a stronger effect on most schizophrenic symptoms. Thus, it seems to be more effective than other agents in severely ill, treatment-resistant patients. Clozapine rarely causes extrapyramidal symptoms such as pseudoparkinsonism or akathisia. To date, no confirmed cases of tardive dyskinesia have been attributed to the drug. Despite these advantages, the usefulness of clozapine is limited by its potentially life-threatening side effects, which include agranulocytosis and respiratory depression. PMID- 1739063 TI - NIH releases statement on depression in the elderly. PMID- 1739064 TI - Clinical application of the ACCO appliance. Part 1. AB - Difficult Class II, Division 1 malocclusions can be successfully treated with a combination of fixed and removable appliances. The clinical application of the Margolis ACCO appliance is demonstrated in a variety of malocclusions through the use of before-treatment progress, and posttreatment records. PMID- 1739065 TI - Patterns of incisor root resorption before and after orthodontic correction in cases with anterior open bites. AB - External root resorption is a frequent iatrogenic consequence of orthodontic treatment, particularly in the maxillary anterior teeth. Since resorption also occurs is a normal function of aging and since altered behaviors such as bruxism and chronic nailbiting accelerate resorption even in the absence of treatment, it was hypothesized that the long-term orthopedic forces of tongue thrusting leading to anterior open bites would also enhance the rates of clastic activity. In a series of 32 adolescents with open bites, the roots of permanent maxillary central incisors were significantly shorter and exhibited higher modal grades of periapical resorption than a matched series with deep bites before treatment. The open bite group also had less facial bony support for these teeth. Both series experienced discernible resorption during full-banded treatment but to comparable extents so that, after active treatment, the open bite series continued to possess significantly greater degrees of resorption. Consequently, the oral forces leading to apertognathia are themselves destructive of root integrity and merit early recognition and interception. PMID- 1739066 TI - Controlled retraction of maxillary incisors. AB - The force characteristics inherent in the prefabricated PG retraction spring have been shown to be efficient for controlled movement of canines. In the present investigation, this spring was analyzed with regard to its applicability for controlled retraction of the maxillary incisors. A description of the required system of moments and horizontal and vertical forces, acting at both the active (alpha) and reactive (beta) units, is presented. The three-dimensional force system generated by specific modifications of the spring was registered in a bench testing device mounted with strain gauges, and the resultant data presented in a graphic. It is concluded that the PG retraction spring can be used as a module for controlled retraction of both canines and incisors. The magnitude of horizontal and vertical forces is kept within the anticipated physiologic limits and can be identified by the shape of the activated spring. Variability of the distance between the anterior and the posterior points of force attack has no significant influence on the horizontal and vertical forces produced. Only minor clinical adjustments are needed to modify the retraction spring from canine-to incisor retraction. PMID- 1739067 TI - Lower arch crowding in the young adult. PMID- 1739068 TI - Comparison of the shear bond strength of a light-cured glass ionomer and a chemically cured glass ionomer for use as an orthodontic bonding agent. AB - Light-cured glass ionomers with an initial set of 20 seconds may produce higher initial bond strengths, as well as decreased sensitivity to moisture contamination and desiccation, than chemically cured glass ionomers making them attractive for use as orthodontic bonding agents. The purpose of this study was to determine and compare the shear bond strength of stainless steel orthodontic attachments to enamel with a light-cured glass ionomer (Zionomer) tested at 60 minutes and 24 hours, and a rapidly setting chemically cured glass ionomer (Ketac Bond) tested at 60 minutes and 24 hours. Fifty-two recently extracted human premolars were randomly divided into four groups--1-hour and 24-hour light-cured glass ionomer groups and 1-hour and 24-hour chemically cured glass ionomer groups. Stainless steel lingual buttons were bonded to prepared enamel surfaces, and the samples were placed in a water bath at 37 degrees C until ready for testing. The shear bond strength of each sample was determined with a universal testing instrument. Results from the study conclude: (1) The mean shear bond strength of the light-cured glass ionomer is greater than that of the chemically cured glass ionomer at 1 and 24 hours. (2) The mean shear bond strength of both glass ionomers increases from 1 to 24 hours. (3) The mean shear bond strength of the light-cured glass ionomer is not significantly different from 1 to 24 hours, but the shear bond strength of the chemically cured glass ionomer cement is different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739069 TI - An example of regional variation in the tempos of tooth mineralization and hand wrist ossification. AB - Two groups of adolescent orthodontic patients, one from the Midwest and one from the Midsouth, were compared to test the clinical impression that the permanent teeth of southern children form and erupt at significantly later ages. Indeed, a marked difference is documented, with the Midsouth series achieving mineralization stages at least 1 1/2 years later on average. This suggests that regional differences are appreciably greater than previously suspected. Clinical consequences revolve on the use of conventional (generally Northeast-based) norms for tooth formation and eruption and predictive models of facial growth. In contrast, the analysis of rates of hand-wrist development (bone age) of these same subjects disclosed no difference; this further confirms the essential independence of development of the dental and osseous tissue systems. PMID- 1739070 TI - Impacted maxillary canines: a review. AB - An overview of the incidence and sequelae, as well as the surgical, periodontal, and orthodontic considerations in the management, of impacted canines is presented. The clinician needs to be familiar with the differences in the surgical management of the labially and palatally impacted canines, the best method of attachment to the canine for orthodontic force application, the advantages of one-arch versus two-arch treatment, and the implications of canine extraction. The various factors that influence all these decisions are discussed. PMID- 1739071 TI - The first direct bonding in orthodontia, revisited. PMID- 1739072 TI - First direct bonding in orthodontia. PMID- 1739073 TI - Risk preclusion. PMID- 1739074 TI - Comments on vertical growth patterns. PMID- 1739075 TI - Comments on increase in arch perimeter. PMID- 1739076 TI - Abnormal urate transport in patients with intracranial disease. AB - Based on our demonstration of a high incidence of hypouricemia, tubular urate transport abnormality, and cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS), we performed prospective renal clearance studies in 29 consecutive neurosurgical patients with intracranial diseases of multiple etiologies to test our hypothesis that patients with intracranial disorders had defective tubular urate transport. Similar studies were performed in 21 age-matched controls. None of the subjects had serum creatinine greater than 123.8 mumol/L (1.4 mg/dL), sickle cell or liver diseases, or received intravenous fluid or uricosuric drugs at the time of study. Seven patients had no surgical procedures, 12 were studied after a neurosurgical procedure, and 10 had preoperative and postoperative studies. Ten had more than one postoperative study. Twelve had 24-hour urine collections. We found that 18 of 29 patients had elevated fractional excretion (FE) of urate greater than 10%. There was no difference in preoperative and postoperative FE urate by nonpaired t test for all patients and by paired t test in the 10 patients who had preoperative and postoperative studies performed. Seven patients had hypouricemia, defined as serum urate less than or equal to 0.18 mmol/L (3 mg/dL). Only one had hyponatremia (serum sodium less than 130 mmol/L). Urate excretion averaged 3.6 +/ 0.32 mmol (603 +/- 52.7 mg)/24 h, suggesting that the hypouricemia was not due to decreased urate production. None of the medications or surgical procedures could be considered to have caused the urate transport abnormality, nor was it associated with any specific intracranial location or type of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739077 TI - Potassium homeostasis with indomethacin therapy in normal subjects. AB - In an attempt to delineate effects of prostaglandin (PG) synthesis inhibition on potassium metabolism in normal subjects, we challenged 13 young, healthy volunteers with a potassium chloride infusion before and after a 4-day course of indomethacin (25 mg orally, three times a day). The plasma potassium level was monitored at 10-minute intervals throughout the 50-minute infusion and for a total of 180 minutes. The maximal increment in plasma potassium level was 0.82 +/ 0.07 mmol/L (mEq/L) in the untreated state, and 0.86 +/- 0.08 mmol/L with indomethacin treatment. The basal potassium level before infusion was higher in the indomethacin-treated than the control state (3.83 +/- 0.07 v 3.68 +/- 0.07 mmol/L; P less than 0.01). Urinary potassium excretion over the 3-hour study period equalled the potassium load administered, and was unaffected by indomethacin therapy. Indomethacin did not alter insulin or aldosterone levels during the study. PGE2 excretion over the 3 hours was lower in the indomethacin than the control phase, although it was higher than normal in both phases. In an additional experiment, the comparative effects of a saline versus saline potassium infusion on PG excretion were studied. No differences were seen between the excretion patterns of PGE2 or 6-keto-PGF1a with the two infusions. We conclude that (1) although basal serum potassium level is slightly higher in healthy young people during indomethacin treatment, there is little effect on handling of an acute potassium load; (2) the aldosterone response to hyperkalemia is PG-independent; (3) urinary PG excretion increases in response to a saline based infusion, but the effect is not enhanced by acute potassium loading. PMID- 1739078 TI - Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma. AB - Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF) alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD. PMID- 1739079 TI - Solute clearances with high dialysate flow rates and glucose absorption from the dialysate in continuous arteriovenous hemodialysis. AB - The purpose of this study was to determine the effects of high inlet dialysate flow rates (IDFR) on the clearances of urea and creatinine and to measure the absorption of glucose through the dialyzer in continuous arteriovenous hemodialysis (CAVHD). Ten anuric acute renal failure patients in the intensive care unit were studied. Increasing the IDFR from 0 to 33.3 mL/min (0 to 2 L/h) produced linear increments in the clearances of urea and creatinine, whereas further increases in the IDFR from 33.3 to 66.7 mL/min (2 to 4 L/h) produced less important, but still significant, increases in the clearances. At 66.7 mL/min, the clearances for urea and creatinine were 48.5 +/- 3.4 and 42.2 +/- 2.5 mL/min, respectively. Using a dialysate with a glucose concentration of 25.3 mmol/L (0.5 g/dL), the net transfer of glucose through the dialyzer did not change significantly, from 16.7 to 66.7 mL/min of IDFR. Increasing the inlet dialysate glucose concentration from 25.3 to 75.8, 126.3, and 214.6 mmol/L (0.5 to 1.5, 2.5, and 4.25 g/dL) at a fixed IDFR of 16.7 mL/min produced linear increments in the net glucose transferred to the patient, from 0.12 +/- 0.02 to 0.67 +/- 0.05, 1.25 +/- 0.06 and 2.30 +/- 0.14 mmol/min, respectively (21.4, 121.0, 225.7, and 414.5 mg/min). No significant changes in the ultrafiltration and plasma flow rates through the dialyzer were recorded at these different IDFR or inlet dialysate glucose concentrations. Ten patients were treated for 4 days or more with 16.7 mL/min (1 L/h) IDFR CAVHD with excellent control over kidney function parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739080 TI - Outpatient vascular access surgery: impact of a dialysis unit-based surgical facility. AB - The present report describes a novel approach to vascular access surgery based on the philosophy that a readily available operating room, staffed by nurses familiar with the unique problems of dialysis patients and their therapy, would reduce dialysis delays and maintain the quality of surgical care. Based on a 28 month experience with more than 1,000 access cases, we conclude that a traditional surgical setting is not necessary for either quality access graft placement or the management of access complications. PMID- 1739081 TI - The Thomas shunt revisited. AB - During a 10-year period, 57 external Thomas femoral shunts (TS) were placed in 43 patients for chronic hemodialysis access. Median shunt survival was 28 months (range, 0.5 to 132). Sixty-three percent (36/57) of shunts are presently functional or functioned until the time of patient death from unrelated cause or removal after renal transplantation. The remaining 37% (21/57) failed after a mean duration of 18 months (range, 2 to 40). Causes of failure were thrombosis (57%), refractory infection (24%), and failure during surgical revision (19%). There were no shunt-related deaths. Race, sex, the presence of diabetes mellitus or hypertension, and prior surgical revision of access did not adversely affect shunt survival. These results support the TS as a viable means of chronic vascular access for hemodialysis patients who cannot receive further upper arm accesses. PMID- 1739082 TI - Clinical experience with short-time hemodialysis. AB - After at least 6 months on conventional hemodialysis (cellulosic dialyzers, acetate dialysate, and a 3- to 4-hour treatment time), 56 patients were changed to short-time hemodialysis (less than 180 minutes) using polysulfone dialyzers and bicarbonate-containing dialysate. Treatment time decreased (191 +/- 5 v 147 +/- 5 min; P = 0.001), while Kt/V (1.22 +/- 0.04 v 1.29 +/- 0.06; P = NS) and normalized protein catabolic rate (pcr) (1.10 +/- 0.05 v 1.10 +/- 0.07 g/kg/d; P = NS) remained constant. When compared with the conventional period, 30 months of short-time hemodialysis resulted in no changes in predialysis blood pressure (BP) (151 +/- 2/84 +/- 1 v 151 +/- 2/86 +/- 1 mm Hg), postdialysis BP (144 +/- 2/81 +/ 1 v 143 +/- 3/84 +/- 1 mm Hg), interdialytic weight gain (2.4 +/- 0.1 v 2.7 +/- 0.2 kg), or blood urea nitrogen (BUN) (26.1 +/- 0.71 v 25.3 +/- 1.07 mmol/L [73 +/- 2 v 71 +/- 3 mg/dL]). Shorter treatment times were not associated with an increase in intradialytic complications. Actually, the frequency (%) of dialysis treatments associated with nausea (5.94 +/- 1.33 v 2.21 +/- 0.52), vomiting (3.12 +/- 0.87 v 0.54 +/- 0.14; P less than 0.05), headaches (5.60 +/- 1.13 v 2.03 +/- 0.52; P less than 0.05), and back pain (0.91 +/- 0.25 v 0.05 +/- 0.05; P less than 0.05) was decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739083 TI - Comparisons of the effects of calcium carbonate and calcium acetate on zinc tolerance test in hemodialysis patients. AB - Because aluminum hydroxide, as a phosphate binder, lowered intestinal zinc absorption, we studied the effects of calcium carbonate (CaCO3) and calcium acetate (CaAc), two other phosphate binders, on intestinal Zn absorption in nine patients on hemodialysis and in 11 controls by measuring 1- and 2-hour serum Zn levels after oral administration of 50 mg of elemental Zn as Zn gluconate with or without concomitant administration of 2 g CaCO3 (800 mg elemental Ca) or 3 g CaAc (750 mg elemental Ca). Fasting serum Zn levels were not different between patients and controls (14.0 +/- 2.3 v 14.1 +/- 1.2 mumol/L [91.8 +/- 14.9 v 92.3 +/- 8.0 micrograms/dL]), but the area under the curve of serum Zn increment (AUC) 2 hours after an oral Zn challenge without or with either of two of phosphate binders used was significantly smaller in patients than in controls (P less than 0.05). The AUC after concomitant administration of Zn with CaCO3 did not differ from that of Zn alone in either patients or controls, but it was significantly less in Zn with CaAc than in Zn alone or in Zn with CaCO3 in both groups. The results demonstrate that intestinal Zn absorption after an oral Zn challenge decreased in patients on hemodialysis and concomitant administration of CaAc, but CaCO3 did not decrease intestinal Zn absorption in either group. PMID- 1739084 TI - Long-term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function. AB - Long-term follow-up data are provided for a previously reported study of patients with membranous glomerulonephritis (MGN), nephrotic syndrome, and renal function impairment. Nine patients were treated with cyclophosphamide (1 to 2 mg/kg) and six of these received concurrent prednisone; they are compared with 17 concurrent controls (14 of whom had received prednisone at some time). The mean follow-up is 83 +/- 13 months in the treated patients and 64 +/- 7 months in the controls. Of the nine treated patients, four achieved a complete remission from the nephrotic syndrome (proteinuria less than 0.5 g/d), and five a partial remission (proteinuria decreased by at least 50% and to less than 3.5 g/d). One of the nine treated patients and 10 of the 17 controls have reached end-stage renal disease (ESRD) (P less than 0.05). Nine of the controls reaching ESRD had persistent nephrotic syndrome, whereas of the seven controls who have not yet reached ESRD, only two have persistent nephrotic syndrome (chi 2, P less than 0.02). There have been four relapses in three treated patients, and three of the four have responded to repeat therapy. One patient refused full therapy and remains nephrotic. Life-table analysis demonstrates significantly increased survival from ESRD in treated patients as compared with controls (P = 0.04). PMID- 1739085 TI - Treatment of membranous glomerulonephropathy. PMID- 1739086 TI - Should the urine PCO2 or the rate of excretion of ammonium be the gold standard to diagnose distal renal tubular acidosis? AB - A high rate of excretion of ammonium (NH4+) during chronic metabolic acidosis should rule out the diagnosis of distal renal tubular acidosis (RTA). Bearing this in mind, the purpose of this report is to demonstrate that a low urine minus blood PCO2 difference in alkaline urine (U-B PCO2) is a less reliable indicator of the diagnosis of distal RTA. The patient who is the subject of this report sniffs glue on a chronic, but intermittent basis. He presented with metabolic acidosis (pH 7.20; bicarbonate, 10 mmol/L) and an anion gap in plasma of 20 mEq/L. The urine anion gap (-14 mEq/L) and osmolal gap (185 mmol/L [mOsm/kg] H2O) suggested that there was a high, rather than a low, rate of excretion of NH4+. This was confirmed by direct measurement of NH4+ in the urine (101 mumol/min). The high rate of excretion of NH4+ suggested that the metabolic acidosis was due, in large part, to an abnormally high rate of production of acid (hippuric acid, because the rate of excretion of hippurate was 76 mumol/min). The U-B PCO2 was low (10 mm Hg) on the second hospital day, after the acidosis was corrected. Potential reasons for the discrepancy between the high rate of excretion of NH4+ and the low U-B PCO2 are discussed. PMID- 1739087 TI - Acute renal failure in hepatitis B virus-related membranous nephropathy with mesangiocapillary transition and crescentic transformation. AB - We report the first case of hepatitis B virus (HBV)-related membranous nephropathy (MN) that progressed to crescentic transformation superimposed on a mixed membranous and mesangiocapillary glomerulonephritis. The patient developed acute renal failure, which partially responded to pulse methylprednisolone therapy, and subsequently recovered after plasma exchange. PMID- 1739088 TI - Fatal destructive cervical spondyloarthropathy in two patients on long-term dialysis. AB - Two patients with fatal cervical cord compressive myelopathy are described, both of whom had been on dialysis for more than 15 years. Destructive changes were noted in mid and upper cervical regions, with soft tissue mass in the atlanto occipital region in one patient. Clinical and radiographic findings suggest both amyloid and hyperparathyroidism as possible etiologies for these destructive spinal changes. Clinicians should be aware that the full picture of quadriparesis may be associated with destructive spondyloarthropathy (DSA) in long-term dialysis patients. PMID- 1739089 TI - An unusual case of renal failure after pregnancy. PMID- 1739090 TI - Surgery in the management of autosomal dominant polycystic kidney disease. PMID- 1739091 TI - Effect of androgen administration on the action of exogenous erythropoietin in hemodialysis patients. PMID- 1739092 TI - Pheochromocytoma in a renal failure patient treated by hemodialysis. PMID- 1739093 TI - Human mesangial cells are resistant to productive infection by multiple strains of human immunodeficiency virus types 1 and 2. AB - Human immunodeficiency virus-associated nephropathy (HIVAN) is a recognized clinical entity of unknown pathogenesis. A role for viral infection of renal cells in the initiation of this process at present is an intriguing but untested hypothesis. Studies in primate models of acquired immunodeficiency syndrome (AIDS) suggest that injury to the mesangial cell may be central to the sclerosing glomerular lesion characteristic of HIVAN. We therefore tested the infectibility of human mesangial cells (HMC) in vitro by a variety of strains of HIV chosen to include a spectrum of tropisms for different cell types. Productive infection of mesangial cells could not be demonstrated using any of the virus strains. Nonetheless, HIV infection of intrinsic renal cells remains an attractive area of inquiry for understanding the natural history of HIVAN. PMID- 1739094 TI - Effect of renal replacement therapy on viscosity in end-stage renal disease patients. AB - Viscosity, an important determinant of microcirculatory hemodynamics, is related to hematocrit (HCT), and may be altered by renal failure or its treatment. To assess these factors, we studied the effect of dialysis on the viscosity of whole blood, plasma, and reconstituted 70% HCT blood of eight continuous ambulatory peritoneal dialysis (CAPD) and nine hemodialysis (HD) patients under steady shear flow conditions at different shear rates, before and after dialysis, compared with nine normal subjects. The density of the red blood cells (RBCs), a marker of cell hydration, was measured in HD patients by a nonaqueous differential floatation technique. Whole blood viscosity was higher in controls than patients, and correlated with HCT before treatment (P less than 0.05) at shear rates of 11.5 to 230 s-1) in HD patients, and 23 to 230 s-1 in all end-stage renal disease (ESRD) patients. In contrast, whole blood viscosity correlated with HCT in CAPD patients only at the lowest shear rates (2.3 and 5.75 s-1, P less than 0.05). Plasma viscosity was higher in CAPD patients than both HD patients before treatment and controls (P less than 0.05, analysis of variance [ANOVA]), despite lower plasma total protein, albumin, and similar fibrinogen concentration compared with HD patients. When all samples were reconstituted to 70% HCT, CAPD patients had higher whole blood viscosity than control subjects'. The high HCT blood viscosity of the ESRD patients was higher than control subjects' at capillary shear rates, suggesting increased RBC aggregation and decreased RBC deformability in patients with renal disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739095 TI - Silicon accumulation in dialysis patients. AB - Plasma silicon measurements have been obtained in patients with end-stage renal disease on chronic dialysis therapy. The mean +/- SE values for normal plasma silicon concentrations are .15 +/- .02 mg/L. All dialysis groups showed marked elevations in their plasma silicon that correlated with the silicon content of their respective dialysis fluids. The values of two different hemodialysis groups and a peritoneal dialysis group were 4.6 +/- .4, 2.5 +/- .2, and 1.9 +/- 1.2 mg/L, respectively. The silicon content of their respective dialysis fluids were 4.0 +/- .7, 0.5 +/- .4, and 0 +/- .1 mg/L. The ultrafiltrability of plasma silicon through Cuprophane membranes was 79 +/- 2%. Hemodialysis patients drinking high-silicon well water showed significantly higher plasma silicon levels than patients drinking lower silicon municipal water. It is concluded that use of dialysis fluid with elevated silicon levels and the consumption of water containing high concentrations of silicon are two important determinants of silicon levels in a dialysis population. We observed no overt effects of silicon accumulation on the health status of our dialysis patients. PMID- 1739096 TI - Serum bactericidal activity for Yersinia enterocolitica in hemodialysis patients: effects of iron overload and deferoxamine. AB - Human serum has been shown to be bactericidal for most strains of Yersinia enterocolitica. Systemic Y enterocolitica infections have been reported in iron overloaded hemodialysis patients treated with deferoxamine. Both iron and deferoxamine are known to enhance the growth of Y enterocolitica. We inoculated sera from 12 hemodialysis patients whose serum ferritin levels ranged from 26 to 6,855 micrograms/mL (ng/mL), as well as three controls, with Yersinia organisms. After latencies of 0 to 24 hours, inoculated sera were then plated on blood agar. Bactericidal activity was demonstrated in all sera and the degree of activity did not correlate with ferritin levels. Bactericidal activity was also demonstrated in sera from three deferoxamine treated patients. We conclude that in vitro, sera of end-stage renal failure patients, with and without iron overload, are as bactericidal as control sera for Y enterocolitica and that deferoxamine therapy does not interfere with that bactericidal activity. PMID- 1739097 TI - Serum calcium increases the incidence of arrhythmias during acetate hemodialysis. AB - We investigated the occurrence of arrhythmias during maintenance acetate hemodialysis (HD) using a 24-hour continuous electrocardiogram recording system. Three of 22 patients showed augmented increases in both ventricular premature beats and supraventricular premature beats during HD. When we changed the dialysate from one with a Ca2+ concentration of 1.75 mmol/L (3.5 mEq/L), to one with a Ca2+ concentration of 1.25 mmol/L (2.5 mEq/L), the elevation of serum Ca2+ concentration during HD was abolished and the increases in both ventricular premature beats and supraventricular premature beats were significantly decreased. The elevation of serum Ca2+ concentration during HD might induce either extracellular or intracellular increase in Ca2+ concentration in the heart and elicit either reentry- or triggered-activity types of arrhythmias during HD. The present results indicate that the dialysate with a lower Ca2+ concentration is advisable to use in patients with underlying cardiac diseases. PMID- 1739098 TI - A comparison of reported sleep disorders in patients on chronic hemodialysis and continuous peritoneal dialysis. AB - There are few data about the prevalence and characteristics of reported sleep disorders in chronic dialysis patients and, although insomnia is often used as a marker of uremia, there are few data relating complaints of sleep to adequacy of dialysis. We therefore surveyed 48 hemodialysis (HD) patients, 22 continuous peritoneal dialysis (PD) patients, and 41 healthy control subjects about disordered sleep. The questionnaire included demographic data, questions characterizing the reported sleep problems, and linear analogue scales quantitating the severity of the sleep disturbance and feelings of anxiety, worry, and sadness. Kt/V determinations were also made for each dialysis patient. Fifty-two percent of the HD, 50% of the PD, and 12% of the control subjects reported problems sleeping (P less than 0.001, all dialysis patients v controls). No differences between HD and PD in characteristics of sleep problems were seen. Sleep severity scale results confirmed sleep disorders (7.2 in those with v 0.95 in those without sleep disorders, where 0 = sleep a little problem and 10 = a big problem, P less than 0.001). Caffeine intake (P less than 0.05) and worry (P less than 0.004) were the only factors associated with reported sleep disturbances. Kt/V values (1.4 +/- 0.3) did not predict reported sleep problems. Mean reported hours of sleep per night (5.5 +/- 2 v 5.8 +/- 1.4) and desired hours of sleep per night (8.3 +/- 2 v 7.6 +/- 1.3) were similar among dialysis patients and controls reporting sleep problems. Dialysis patients and controls without self-reported sleep disorders slept a mean of 7.1 +/- 2.4 and 7 +/- 1.1 h/night, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739099 TI - Polymicrobial peritonitis in patients on continuous peritoneal dialysis. AB - Little data are available about the characteristics, outcome, and risk factors for polymicrobial peritonitis in patients on continuous peritoneal dialysis. We therefore reviewed the 43 episodes of polymicrobial peritonitis that occurred in 39 of our patients over the 11.5 years of our program. Polymicrobial peritonitis represented 9% (43/492) of all peritonitis episodes. Only three episodes of polymicrobial peritonitis were associated with an enteric source. Sixteen percent (7/43) of the polymicrobial peritonitis episodes were associated with catheter infections. Staphylococcus aureus was one of the cultured organisms in 33% of the polymicrobial peritonitis episodes. Patients with polymicrobial peritonitis had higher rates of tunnel infection (0.28/yr v 0.18/yr) and overall peritonitis (1.23/yr v 0.81/yr) than patients with single-organism peritonitis. Black patients were more likely to have polymicrobial peritonitis (12/56 v 27/338 whites, chi 2 = 9.8, P less than 0.005). Patient age, gender, time on peritoneal dialysis, insulin dependence, and cause of end-stage renal disease had no influence on polymicrobial peritonitis. Significantly more catheters were removed for polymicrobial peritonitis than for single-organism peritonitis (17/42 v 89/420, chi 2 = 7.05, P less than 0.01), but in 60% of the episodes, the polymicrobial peritonitis was successfully treated without catheter removal. Polymicrobial peritonitis often occurs without gram-negative organisms and extension of catheter infection may be involved in some cases. For unclear reasons, black patients are at higher risk of polymicrobial peritonitis. PMID- 1739100 TI - Effect of pregnancy on long-term function of renal allografts. AB - Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension. PMID- 1739101 TI - Pregnancy in the renal transplant patient. PMID- 1739102 TI - Hyperlipidemia associated with alpha-mercaptopropionylglycine therapy for cystinuria. AB - Treatment of cystinuria with alpha-mercaptopropionylglycine has been associated with fewer side effects than traditional therapy with D-penicillamine. In this report, we describe a patient who developed hyperlipidemia secondary to alpha mercaptoproprionylglycine therapy. This abnormality resolved after the therapy was discontinued and did not recur with lower dose therapy. Patients treated with alpha-mercaptoproprionylglycine should be monitored closely for the development of lipid abnormalities. PMID- 1739103 TI - B-cell lymphoma presenting as infiltrative renal disease. AB - Acute renal failure is rarely the presenting manifestation of non-Hodgkin's lymphoma. Of the reported cases of renal insufficiency secondary to diffuse renal infiltration with lymphoma, few have presented with acute renal failure. We present a patient with acute renal failure secondary to diffuse bilateral renal infiltration by a B-cell non-Hodgkin's lymphoma. The findings of an elevated serum lactate dehydrogenase (LDH), lymphopenia, and homogenous bilateral renal enlargement on computed tomographic (CT) imaging were important in suggesting the diagnosis of primary renal lymphoma. Renal biopsy with immunohistochemical and ultrastructural analysis was instrumental in confirming this diagnosis. PMID- 1739104 TI - Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis? AB - Immunotactoid glomerulopathy (IT), or alternatively, microtubular glomerulopathy, is a term that has been used by some investigators to encompass those glomerulopathies characterized by the presence of fibrillar or microtubular deposits which are distinguished from amyloid principally by their larger size and lack of reactivity with the Congo red reagent. A case is presented here of IT as it was initially described. The present case, and a review of the literature, suggest that the diagnosis of IT be restricted to those glomerulopathies associated with large, at times organized, microtubular deposits. Terms such as fibrillary glomerulonephritis, or alternatively Congo red-negative amyloidosis like glomerulopathy, could then be used to describe those patients with smaller, fibrillar glomerular deposits having an appearance closely resembling amyloid. We believe it is possible to separate the entities fibrillary glomerulonephritis and IT on morphological grounds. This is a potentially useful distinction that identifies patients who are likely to have or develop clinical evidence of a lymphoplasmacytic disorder or dysproteinemia, which are associated with deposits of IT, and distinguishes them from patients with fibrillary glomerulonephritis, of whom only a single case has been linked to such clinical findings. PMID- 1739105 TI - Contribution of urinary titratable acid to acid-base homeostasis. PMID- 1739107 TI - Undercover nursing. PMID- 1739106 TI - Musculoskeletal complications after renal transplantation: pathogenesis and treatment. AB - Renal transplantation is associated with several abnormalities of function and structure of the musculoskeletal system. Some of these skeletal problems result from incomplete resolution of abnormalities of bone and mineral metabolism present at the time of transplantation. In this regard, persistent hyperparathyroidism, diabetes mellitus type 1, and accumulation of beta 2 microglobulin may lead to residual skeletal effects despite excellent function of the allograft. Persistent hyperparathyroidism may accelerate bone loss and increase the risk for osteonecrosis, as well as cause hypercalcemia and hypophosphatemia; some patients with severe hyperparathyroidism require parathyroid surgery. Osteonecrosis is the most debilitating skeletal complication after transplantation and frequently requires surgical therapy. Although osteomalacia associated with aluminum overload generally resolves after transplantation, bone complications due to dialysis amyloidosis and diabetes mellitus type 1 often fail to improve. Alternatively, skeletal abnormalities can be acquired after transplantation. Most of the new derangements of bone and mineral metabolism are due to the immunosuppressive medications. Toxic effects of glucocorticoids on bone contribute to the pathogenesis of osteonecrosis, increase the risk for fractures by decreasing cancellous bone mass and synthesis of bone matrix, and dampen the linear growth response in pediatric recipients. Whether cyclosporine independently causes appreciable toxic effects on bone metabolism is not yet clear, but use of this drug increases the prevalence of gout and dental problems. Osteonecrosis, osteopenia, and short stature remain important skeletal complications in recipients of renal allografts. Therapeutic efforts should be directed toward alleviating pretransplant bone disease and attenuating bone loss after transplantation. PMID- 1739108 TI - New roles for interferon-alpha? PMID- 1739109 TI - Healthy reform or exacerbated status quo? PMID- 1739110 TI - More on hospice six. PMID- 1739111 TI - Steroidphobia and the pulmonary patient. PMID- 1739112 TI - Why give corticosteroids for Pneumocystis carinii pneumonia? PMID- 1739113 TI - Use a decision tree to choose wound dressings. PMID- 1739114 TI - MRSA: Pandora's box for hospitals. PMID- 1739115 TI - Job focus. Rehab: 'primary nursing as it was meant to be.'. PMID- 1739116 TI - NMS: rare and dangerous drug reaction. PMID- 1739117 TI - Job focus. Your guide to nursing opportunities on the West Coast. PMID- 1739118 TI - The staph that eats hospitals. PMID- 1739119 TI - Pointing out medication errors. PMID- 1739120 TI - Eggs mean murder. PMID- 1739121 TI - Casein kinase II alteration precedes tau accumulation in tangle formation. AB - Previous studies have shown altered casein kinase II (CK-II) in Alzheimer's disease (AD). For the present study, the authors analyzed CK-II immunoreactivity at various stages of tangle formation using quantitative laser confocal microscopy and immunoelectron microscopy. AD hippocampal pyramidal cells without neurofibrillary tangles (NFTs) displayed 15% more anti-tau immunoreactivity (P less than 0.01) and 43% more anti-CKII immunolabeling than controls (P less than 0.001). In AD, tangle-bearing hippocampal neurons with strong anti-tau immunoreactivity (threefold increase from controls) showed a significant 22% increase in anti-CKII immunolabeling (P less than 0.01), compared with those without NFTs. Neurons with early neurofibrillary changes showed diffuse anti-CKII immunostaining in their cytoplasm and cell processes. In tangle-bearing neurons, in which a higher level of tau immunoreactivity was detected, anti-CKII immunolabeling was distributed along a fibrillar meshwork in cell bodies and processes. Linear regression analysis of anti-CKII and anti-tau immunoreactivity in AD showed a positive correlation (r = 0.53, P less than 0.001). At the ultrastructural level, anti-CKII was immunolocalized to the paired helical filaments (PHF) of the tangle-bearing neurons, as well as to PHF in neuropil threads and some dystrophic neurites in plaques. These results suggest a possible role for CK-II in tangle formation. PMID- 1739122 TI - Beta protein immunoreactivity is found in the majority of neurofibrillary tangles of Alzheimer's disease. AB - The presence of dystrophic neurites in most extracellular neurofibrillary tangles (E-NFT) suggests a factor promoting neurite growth in E-NFT. Although the beta protein detected in E-NFT may fill that role, reports that only 2-10% of E-NFT contain beta-protein whereas 80-100% contain dystrophic neurites suggested that beta-protein does not play an important role. In this study, the authors used two antisera and one monoclonal antibody to beta-protein to establish the effects of tissue preparation and formic acid enhancement on the detection of beta-protein in E-NFT. We found that beta-protein epitopes in E-NFT are sensitive to formaldehyde fixation and are best enhanced by 50% formic acid, whereas beta protein in senile plaques is best enhanced at higher formic acid concentrations. After treatment with 50% formic acid, beta-protein was found in all E-NFT. Interestingly, after treatment with 10% formic acid, half of intraneuronal-NFT (I NFT) also contained beta-protein immunoreactivity. The finding that beta-protein immunoreactivity in senile plaques, E-NFT and I-NFT is increased at different formic acid concentrations suggests that beta-protein in each location is in a different conformation. In contrast, no beta-protein immunoreactivity could be found in E-NFT of the brain stem, an area in which dystrophic neurites do not infiltrate E-NFT. These findings indicate a correlation between neuritic infiltration and presence of beta-protein in E-NFT and suggests the two are linked in Alzheimer's disease for E-NFT as well as senile plaques. PMID- 1739123 TI - Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. AB - In this study, the authors demonstrate the expression of mRNA and the presence of protein for macrophage colony-stimulating factor (MCSF) in atherosclerotic lesions from humans and rabbits. In situ hybridization of serial sections of human fatty streaks demonstrated expression of MCSF mRNA by cells dispersed throughout the lesions. Immunocytochemical staining with a panel of MCSF-specific antibodies showed extensive cell-associated staining of all of the cell types in the lesions. Immunocytochemical studies of atherosclerotic lesions from Watanabe heritable hyperlipidemic (WHHL) and cholesterol-fed rabbits demonstrated a similar cell-associated pattern of staining. There was no MCSF-specific staining of aortas from normal rabbits or of cultured aortic smooth muscle cells from either humans or rabbits. Macrophage-derived foam cells (MFC) were isolated from the aortas of ballooned, cholesterol-fed rabbits. A Northern blot demonstrated that RNA isolated from the MFC hybridized with a human cDNA probe for MCSF. RNA from alveolar macrophages isolated simultaneously from the same rabbits did not hybridize with the MCSF probe. Conditioned media from an 18- to 24-hour incubation of the MFC contained colony-stimulating activity as demonstrated in a mouse bone marrow culture assay. Most of this colony-stimulating activity was neutralized by preincubating the conditioned media with an MCSF-specific antibody. PMID- 1739124 TI - Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. AB - The infiltration of monocytes into the vascular wall and their transformation into lipid-laden foam cells characterizes early atherogenesis. Macrophages are also present in more advanced human atherosclerotic plaques and can produce many mediators that may contribute to lesion formation and progression. Macrophage colony-stimulating factor (MCSF) enhances the proliferation and differentiation of monocyte progenitors and is required for the survival and activation of mature monocytes and macrophages. The authors therefore examined the expression of the MCSF gene in cultured human vascular endothelial (EC) and smooth muscle cells (SMC) as well as in atheromatous lesions from rabbits and humans. Growth arrested EC and SMC contain a low level of MCSF mRNA. Bacterial lipopolysaccharide (LPS), recombinant human interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF alpha) induced MCSF mRNA accumulation in a concentration-dependent manner in both EC and SMC. These stimuli induced large increases in MCSF mRNA with peak induction between 4-8 hours after treatment. LPS, IL-1 alpha, and TNF alpha stimulated EC and SMC also showed increased fluorescent antibody staining for MCSF protein and released immunoreactive MCSF in a time-dependent manner. In contrast, phorbol 12-myristate 13-acetate (PMA) was a less potent inducer of MCSF gene expression and iron-oxidized low-density lipoproteins (ox-LDL) did not increase consistently MCSF mRNA or the synthesis and secretion of immunoreactive protein. Northern analysis of mRNA isolated from the atheromatous aorta of rabbits fed a 1% cholesterol diet for 10 weeks showed elevated MCSF mRNA compared with controls. Immunostaining of atheromatous arterial lesions of rabbits demonstrated MCSF protein in association with intimal SMC as well as macrophages. Furthermore, polymerase chain reaction (PCR) analysis of MCSF mRNA in human atheromata showed higher levels than found in nonatherosclerotic arteries and veins. Since the authors found no mRNA for the MCSF receptor, c-fms, in cultured EC or SMC macrophages are likely the primary target for MCSF within atheromatous vessels. The authors therefore investigated the effects of MCSF on monocyte functions related to foam cell development. Treatment of cultured human monocytes with recombinant human MCSF (10(3) U/ml, 72 hr) led to the accumulation of mRNA for the acetyl-LDL (scavenger) receptor and apolipoprotein E (apo E). These studies establish that vascular EC and SMC produce substantial MCSF in response to a variety of stimuli. The local production of MCSF during atherogenesis may contribute to macrophage survival and proliferation or activate specific macrophage functions such as expression of the scavenger receptor and secretion of apo E. PMID- 1739125 TI - Histologic findings after in vivo placement of small intestine submucosal vascular grafts and saphenous vein grafts in the carotid artery in dogs. AB - A small caliber vascular graft from porcine small intestine submucosa (SIS) was implanted in a canine carotid artery (n = 24) and compared with an autogenous saphenous vein graft that was implanted in the contralateral carotid artery. In this study, four grafts were evaluated at the following times after surgery: 2, 7, 14, 28, 90, and 180 days. One SIS graft thrombosed at 2 days, two SIS and two saphenous vein grafts were thrombosed at 90 days, and one SIS and one saphenous vein graft were thrombosed at 180 days. At 2 days after implant, the luminal surface of the SIS graft was covered by a thin (30 mu) fibrin meshwork. By 14 days after surgery, endothelial cells on the fibrin meshwork were staining for FVIII-related antigen. Smooth muscle cells were observed in the new intima (fibrin meshwork) by 28 days. At 90 days, both types of graft had arterialized with an intima covered by endothelium, a smooth muscle media, and marked adventitial fibrosis. Similar histology was observed at 180 days. These results indicate that this SIS graft was similar to saphenous vein graft in the dog. PMID- 1739126 TI - Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum. AB - Because Plasmodium berghei ANKA induces cerebral malaria and P. vinckei does not, the former has often been studied as a model for human falciparum malaria. It lacks, however, many of the systemic changes seen in the human disease. Because both of these murine models and the human disease have now been defined in terms of excess tumor necrosis factor (TNF) production, the authors have more closely examined the two murine models in this light to see which provides the better overall model for falciparum malaria. Administering TNF to malaria-infected mice did not cause cerebral symptoms nor breakdown of the blood-brain barrier, which is the hallmark of P. berghei ANKA cerebral malaria and is generally absent in human cerebral malaria. Tumor necrosis factor did, however, induce hypoglycemia and liver injury, pathology that is seen in terminal P. vinckei and falciparum malaria, but is absent in terminal P. berghei ANKA malaria. Plasma TNF and interleukin-6 (IL-6) also were found to be consistently higher in infections caused by P. vinckei than in those caused by P. berghei ANKA. The pathology of P. vinckei malaria is thus consistent with raised systemic levels of TNF and other cytokines, as is falciparum malaria. The authors therefore conclude that P. vinckei malaria, although lacking a cerebral component, is the better model for the human disease. PMID- 1739127 TI - Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation. AB - The expression of aromatase was evaluated in 38 breast carcinomas by an immunohistochemical method (ABC) using an specific polyclonal antibody against human placental aromatase. Fifteen tumors (40%) showed significant immunoreactivity, as defined by cytoplasmic positivity of moderate intensity present in at least 15% of the cells. The results were correlated with the estrogen and progesterone hormone receptor status and several clinicopathologic parameters such as age, tumor size, lymph node status, and stage of the disease. There was a significant, but inverse, correlation between the aromatase activity and the estrogen receptor status (P = 0.04), indicating the likelihood of negative estrogen if substantial aromatase activity was present. No statistically significant correlation was found between the presence of intratumoral aromatase and the rest of the parameters studied (P greater than 0.7). Nor was there a correlation between the aromatase content of the tumors and the menopausal status. The degree of intratumoral heterogeneity of the aromatase content was minimal in six cases where multiple samples from each tumor were analyzed. This is the first study reporting the detection of aromatase in archival material from breast carcinomas using immunohistochemical techniques. The lack of biologic significance of its presence in breast cancer reported here and by others using biochemical assays should be validated in larger series with longer follow-up. The method described can be readily used for that objective. PMID- 1739128 TI - Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions. AB - Alpha B-crystallin, a major protein of the vertebrate lens, is found in the central nervous system (CNS) and is a major protein component of Rosenthal fibers (RF), intracytoplasmic inclusions within astrocytes. Its level of expression in the normal CNS is low and appears to be confined to glial cells, both astrocytes and oligodendrocytes. A number of human brains displaying a variety of pathologic changes were examined by immunohistochemistry with an anti-alpha B-crystallin antiserum and increased immunoreactivity was found in astrocytes and oligodendrocytes without the formation of RFs. Furthermore, some neurons in neurodegenerative disorders were also immunolabeled with the anti-alpha B crystallin antiserum. Thus, the accumulation of alpha B-crystallin appears to be part of the repertoire of reactive processes of CNS glial cells and some neurons in pathologic conditions. PMID- 1739129 TI - Extracellular matrix protein gene expression in atherosclerotic hypertensive pulmonary arteries. AB - Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models. PMID- 1739130 TI - Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas. AB - Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms. PMID- 1739131 TI - Immunopathologic analysis of human urinary bladder cancer. Characterization of two new antigens associated with low-grade superficial bladder tumors. AB - The authors have further characterized the normal human tissue distribution and tumor expression of two highly restricted tumor-associated antigens, detected by mouse monoclonal antibodies M344 and 19A211, which are primarily expressed on low grade superficial urinary bladder tumors. This study was conducted using immunohistochemical staining of frozen and deparaffinized sections of human normal and tumor tissues. The antigens are stable and well preserved on deparaffinized tissue sections. M344 antibody identifies a high-molecular-weight determinant on a cytosolic protein component of over 300,000 Mr. This antigen was not detected on any normal tissue analyzed, including 14 specimens of normal urothelium and 22 cases of cystitis; however, M344 was positive in 74.5% of Ta-T1 tumors and 11% of T3-T4 tumors. 19A211 antibody identifies a sialylated epitope on a cytoplasmic protein complex of 100,000 to 200,000 Mr. This antigen also was expressed preferentially on low-grade superficial bladder tumors (77% Ta-T1) and less frequently on deeply infiltrating tumors (10% T3-4). 19A211 was negative on all normal cells tested, with the exception of umbrella cells, in approximately 25% of the normal urothelium and cystitis specimens studied. Either one or both of these tumor-associated antigens are detected in approximately 80% of low-grade papillary superficial tumors and carcinoma in situ of the urinary bladder. The expression of these antigens on a subset of low-grade bladder tumors, known to progress in only about 10% of cases, suggests that phenotypic differences may reflect biologic potential. Beyond their possible biologic significance, antibodies M344 and 19A211 may provide clinically useful probes for early detection and stratification of urinary bladder tumors. PMID- 1739132 TI - Expression and function of heterotypic adhesion molecules during differentiation of human skeletal muscle in culture. AB - The infiltration of skeletal muscle by leukocytes occurs in a variety of myopathies and frequently accompanies muscle degeneration and regeneration. The latter involves development of new myofibers from precursor myoblasts, and so infiltrating cells may interact with muscle at all stages of differentiation. The authors have investigated the surface expression of ligands for T-cell adhesion during the differentiation of human skeletal muscle in vitro. Myoblasts expressed low levels of ICAM-1 (CD54), which remained constant during muscle cell differentiation and could be induced by cytokines such as gamma-interferon. It is therefore likely that ICAM-1 is involved in the invasive accumulation of lymphocytes during skeletal muscle inflammation. In contrast, LFA-3 (CD58) was expressed at higher levels than ICAM-1 on myoblasts, decreased significantly during myogenesis, and was unaffected by immune mediators. Both ICAM-1 and LFA-3 were able to mediate T cell binding to myoblasts, whereas adhesion to myotubes was independent of the LFA-3 ligand. Although expressed throughout myogenesis, human leukocyte antigen class I and CD44 did not appear to mediate T cell binding. The expression of ligands that facilitate interaction of myogenic cells with lymphocytes may have important implications for myoblast transplantation. PMID- 1739133 TI - Porcine von Willebrand disease and atherosclerosis. Influence of polymorphism in apolipoprotein B100 genotype. AB - The relationship of apolipoprotein-B genotype (Lpb) to diet-induced hypercholesterolemia and atherosclerosis was studied in von Willebrand disease (vWD) and normal pigs. Von Willebrand and normal pigs developed comparable levels of hypercholesterolemia (respectively, 757.9 +/- 49.4 versus 772.8 +/- 47.9 mg/dl, P = 0.95). Pigs with Lpb1/5 and Lpb5/8 genotypes, however, developed significantly higher serum cholesterol levels than those with other Lpb genotypes (866.1 +/- 64.0 mg/dl, P = 0.0343). Coronary and aortic atherosclerosis, measured by computer-assisted automated image analyzer, were not significantly different between vWD and normal pigs. Pigs with an Lpb5 allele developed significantly more atherosclerosis than those with the Lpb3/8 or Lpb8/8 genotypes or the rare Lpb1 allele (r greater than or equal to 0.434, P less than or equal to 0.05). Polymorphism in apolipoprotein B100 genotype, then, significantly influenced the severity of diet-induced hypercholesterolemia and atherosclerotic plaque formation in vWD and normal swine without regard to the vWD genotype. PMID- 1739134 TI - Vascular expression of glucose transporter in experimental brain neoplasms. AB - Vascular abnormalities in brain neoplasms are important to tumor biology and therapy. Glucose transporter (GLUT1) expression is a differentiated property of normal cerebral microvessels typically associated with expression of the blood brain barrier. We investigated the relationship of GLUT1 expression to other vascular characteristics in F98, 9L, and C6 gliomas and Walker 256 carcinomas implanted into adult rat brains. The percentages of microvessels with immunohistochemically detectable GLUT1 were 95.5 +/- 3.9 in F98, 60.9 +/- 3.9 in 9L, 45.4 +/- 5.6 in C6, and 1.2 +/- 0.3 in Walker 256 (mean +/- SEM). The percentage of GLUT1-positive vessels in F98 was not statistically different from that in normal brain. GLUT1 expression was not dependent on restricted permeability as all tumors were highly permeable to Evans blue. GLUT1 expression was unrelated to vascular density, vascular morphology, and parenchymal GFAP expression. The expression of GLUT1, a marker of cerebral endothelial differentiation, is a newly described property of glial tumor vessels that may have diagnostic and prognostic significance. PMID- 1739135 TI - Characterization of uterine epithelium apoptotic cell death kinetics and regulation by progesterone and RU 486. AB - The authors show here that progesterone suppresses apoptosis, and its antagonist RU 486 induces it in rabbit uterine epithelium, as assessed by morphologic and biochemical studies. The authors' studies demonstrate that internucleosomal DNA fragments are identifiable as early as 24 hours after ovariectomy of pseudopregnant rabbits, and become undetectable 6 days after ovariectomy. Maximal levels of DNA fragmentation (about 74% of total isolated DNA) were observed 36 hours after ovariectomy. The number of apoptotic cells appeared to increase parallel to the increased DNA breakdown, and accounted for approximately 26% of the uterine epithelial cells at 48 hours after ovariectomy. Levels of progesterone in serum dropped precipitously 6 hours after ovariectomy and remained very low for several days. Administration of progesterone, more than any other steroid hormone, to pseudopregnant ovariectomized rabbits, prevented the increase in apoptotic cell death. By contrast, administration of the anti progestin RU 486 to pseudopregnant rabbits triggered apoptosis, which attained levels similar to those observed in ovariectomized animals. The authors' findings establish that uterine epithelium apoptosis occurs in a time-dependent fashion and provides strong evidence that the actions of progesterone in that tissue are not only to stimulate cell proliferation and differentiation, but also to suppress apoptosis. PMID- 1739136 TI - Protection of human umbilical vein endothelial cells by glycine and structurally similar amino acids against calcium and hydrogen peroxide-induced lethal cell injury. AB - Cultured human umbilical vein endothelial cells treated with either the calcium ionophore, ionomycin, or ionomycin plus cyanide-m-chlorophenylhydrazone had immediate severe depletion of adenosine triphosphate, (ATP) and increases of cytosolic free calcium (Caf) and then sustained lethal cell injury as manifested by release of lactate dehydrogenase and failure to exclude vital dyes within 15 minutes. Inclusion of glycine in the experimental medium prevented the enzyme leakage for at least 60 minutes without altering the ATP depletion or increases of Caf. The physiologic glycine concentration of 0.25 mmol/l gave 50% protection, and protection was complete at 1 mmol/l. Several other small neutral amino acids, L- and D-alanine, beta-alanine, 1-aminocyclopropane-1-carboxylate, alpha aminoisobutyrate, and L-serine, had effects similar to glycine, but other amino acids and metabolic substrates did not. The endothelial cells were relatively resistant to damage from hydrogen peroxide, but sensitivity could be increased by preloading with Fe2+. In both non-loaded and Fe(2+)-loaded cells, hydrogen peroxide-induced lactate dehydrogenase (LDH) release developing over 180 minutes was prevented by glycine in a fashion analogous to that seen with ionomycin damage. Mn2+ also partially protected against hydrogen peroxide injury but was not required for glycine's effects. These data demonstrate that striking modulatory effects of glycine and structurally similar amino acids that have previously been characterized in most detail using kidney tubule cells are strongly expressed in human umbilical vein endothelial cells and are involved in their response to Ca2+ and oxidant-mediated damage. These amino acid effects must be considered in the design of in vitro studies of endothelial cell injury and may contribute to endothelial cell pathophysiology in vivo. PMID- 1739137 TI - Establishment and characterization of five new human renal tumor xenografts. AB - Ten different human renal cell carcinoma (RCC) primary tumors were xenografted into BALB/c nu/nu mice. Five of the tumors (NU-10, NU-12, NU-20, NU-22, and NU 28) gave rise to serially transplantable tumors that were further characterized. Histology, DNA index, immunohistochemical characteristics, growth rate, and clonogenic potential were followed from primary tumor to the 5th to 15th transplant passage. Only one of the tumors (NU-20) showed remarkable instability for all tested parameters in the first five transplant passages. Histology of the other tumors was essentially the same to the histology of the primary tumors, although differences between human and host-derived vessels were apparent. DNA index values in general showed a trend toward an aneuploid character of the xenografts. Immunohistochemical analyses showed a loss of intensity of staining but a concomitant rise in the fraction of positively staining cells with antibodies against cytokeratins, vimentin, tumor-associated antigens, and human leukocyte antigen (HLA) class I antigens. Human leukocyte antigen class II antigen expression showed a loss of intensity as well as a decrease in the fraction of positive cells. Tumor doubling time was lowest in transplant passage number 0, and stable growth was noticed in transplant passages 1 through 4. Clonogenic potential of four of the lines was higher for the xenografts than for the primary tumors. The authors conclude that, on xenografting, histologic characteristics of the primary tumor are essentially conserved. Progression in the first transplant passages, however, results in tumors with a more aggressive character. PMID- 1739138 TI - Tissue eosinophilia and eosinophil degranulation in syndromes associated with fibrosis. AB - Eosinophilia has long been associated with endomyocardial fibrosis, but the involvement of the eosinophilia in fibrosis of other organs is unclear. To investigate this question, the authors tested whether tissue eosinophilia and eosinophil degranulation are present in syndromes associated with fibrosis. The authors used an indirect immunofluorescent technique to localize eosinophil granule major basic protein (MBP) in formalin-fixed, paraffin-embedded tissue specimens from 50 patients. Thirty-four specimens were obtained from patients with inflammatory fibrosis: 12 with idiopathic retroperitoneal fibrosis, seven with sclerosing mediastinitis, four with sclerosing cholangitis, and 11 with pulmonary fibrosis. The remaining 16 specimens were obtained from patients with noninflammatory fibrous proliferations: four with keloids, six with scars, three with Dupuytren's contracture and three with dense stromal fibrosis of the breast. Eosinophil infiltration and/or extracellular MBP deposition were observed in 28 of the 34 specimens (82%) from patients with inflammatory fibrosis, including 11 of the 12 cases of retroperitoneal fibrosis, five of the seven cases of sclerosing mediastinitis, all four cases of sclerosing cholangitis, and 8 of the 11 cases of pulmonary fibrosis. In contrast, eosinophil infiltration and MBP deposition were not observed in specimens from the 16 patients with noninflammatory fibrous proliferation (P less than 0.001). These results indicate that eosinophil infiltration and release of a granule protein, namely MBP, commonly occur in inflammatory fibrotic lesions. PMID- 1739139 TI - Women health workers: past and present. PMID- 1739140 TI - Men who have sex with men: continued challenges for preventing HIV infection and AIDS. PMID- 1739141 TI - Prevention: the cost-effectiveness of the California Diabetes and Pregnancy Program. AB - BACKGROUND: The California Diabetes and Pregnancy Program is a new preventive approach to improving pregnancy outcomes through intensive diabetes management preconception and early in pregnancy. METHODS: Hospital charges and length of stay data were collected on 102 program enrollees and 218 control cases. Ninety program enrollees and 90 control cases were matched on mother's age. White's classification, and race. Regression models controlled for these variables in addition to MediCal status, birth weight, and enrollment in the program. RESULTS: Hospital charges were about 30% less for program participants and days in the hospital were roughly 25% less. The program effects were larger for women that enrolled before 8 weeks gestation. More serious diabetics were also found to have larger reductions in charges and days. CONCLUSION: After adjusting for inflation and differences in charges across hospitals, $5.19 is saved for every dollar spent on the program. PMID- 1739142 TI - Maternal smoking and the risk of polyhydramnios. AB - BACKGROUND: Washington State birth certificates were used to conduct a population based case-control study to assess the possible association of maternal smoking with polyhydramnios. METHODS: All singleton births complicated by polyhydramnios (n = 557) were identified from the vital records for the years 1984 to 1987. For comparison, 1671 records were randomly selected for the same years from singleton births uncomplicated by polyhydramnios. RESULTS: Women who reportedly smoked prenatally were found to be at increased risk for polyhydramnios (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.5-2.1, adjusted for marital status, maternal age, and parity). When women with conditions known to be associated with polyhydramnios were excluded, the risk for those who smoked prenatally remained elevated (RR = 1.8, 95% CI = 1.1-2.3). CONCLUSION: Overdistention of the uterus from polyhydramnios may cause a variety of pregnancy complications. The observed association of smoking with polyhydramnios may be a further indication for public health interventions aimed at preventing smoking during pregnancy. PMID- 1739143 TI - A cost-effectiveness analysis of three staffing models for the delivery of low risk prenatal care. AB - BACKGROUND: Health care costs are increasing at more than twice the rate of inflation, thus, public officials are seeking safe and economic methods to deliver quality prenatal care to poor pregnant women. This study was undertaken to determine the relationship between the cost and effectiveness of three prenatal clinic staffing models: physician based, mixed staffing, and clinical nurse specialist with physicians available for consultation. METHODS: Maternal and neonatal physiological outcome data were obtained from the hospital clinical records of 156 women attending these clinics. The women were then interviewed concerning their satisfaction with their prenatal care clinic. The financial officer from each clinic provided data on the clinic staffing costs and hours of service. RESULTS: There were no differences in outcomes for the maternal-neonatal physiological variables, although newborn admission to the Neonatal Intensive Care Unit (NICU) approached significance among the clinics. The clinic staffed by clinical nurse specialists had the greatest client satisfaction and the lowest cost per visit. CONCLUSIONS: The use of clinical nurse specialists might substantially reduce the cost of providing prenatal care while maintaining quality, and might thereby save valuable resources. PMID- 1739144 TI - Medicaid prenatal care: a comparison of use and outcomes in fee-for-service and managed care. AB - BACKGROUND: To control rising costs, state Medicaid agencies are enrolling recipients in managed care health plans (MCPs). We performed this study to assess this policy's impact on accessibility and outcomes of Medicaid-funded prenatal care. METHODS: We performed a retrospective, controlled study with three cohorts: a study group of 1106 Medicaid recipients enrolled in three MCPs, a matched comparison group of 4830 recipients receiving care in the fee-for-service (FFS) system, and a second matched comparison group of 4434 non-Medicaid enrollees of the same MCPs. Data on prenatal care use and birth outcomes were obtained through linkage of claims and discharge files with birth certificate files. RESULTS: Medicaid recipients enrolled in MCPs used prenatal care similarly to those in the FFS system and showed equal or modestly improved birth-weight distributions. However, Medicaid MCP enrollees showed poorer use of prenatal care and birth outcomes compared with non-Medicaid enrollees of the same plans. CONCLUSIONS: Enrollment in MCPs has a neutral or small beneficial effect on the prenatal care received by the Medicaid population. However, providing financial access and modifying the system of care for this population did not result in parity with the general population. PMID- 1739145 TI - Attitudes about infertility interventions among fertile and infertile couples. AB - BACKGROUND: There has been marked progress in the development of infertility interventions. This paper reports attitudes about 11 interventions for infertility. METHODS: Face-to-face interviews were conducted with each member of 185 infertile and 90 presumed fertile couples in southeastern Michigan. RESULTS: Seven of these interventions were generally viewed favorably and four were generally viewed negatively, regardless of the couple's fertility status. Infertile couples viewed all interventions, except for adoption, more favorably than did fertile couples. Multidimensional scaling was used to cluster the interventions according to similarity in endorsement. These clusters form a continuum from interventions that allow only one member of the couple to be a biological parent to the most noninvasive techniques. All clusters remain roughly equidistant from adoption, in which neither member of the couple is a biological parent. CONCLUSIONS: Interventions that produce a child who is biologically related to only one member of the couple were viewed most negatively. Members of couples who were receiving fertility treatment made finer discriminations among infertility interventions than did individuals who had not received treatment. PMID- 1739146 TI - Nonclinical factors associated with surgery received for treatment of early-stage breast cancer. AB - BACKGROUND: Women diagnosed with early breast cancer have had the opportunity to receive breast-conserving surgical treatment, which reduces the physical and psychological morbidity heretofore associated with breast removal. METHODS: Nonclinical factors associated with women receiving partial mastectomies with radiation (P + R) compared with modified radical mastectomies without radiation (MOR) were examined in 2238 Black and White women diagnosed, in 1985 through 1987, with early-stage breast cancer in the metropolitan Detroit area. RESULTS: Age at diagnosis and size of hospital were the strongest predictors of type of surgery received, with younger women (less than 55 years of age) and women treated in larger hospitals (more than 500 beds) more than twice as likely to receive P + R. Stratifying on race, age at diagnosis remained the strongest predictor for White women, followed by hospital size. Among Black women, hospital size was more strongly associated with surgery received than was age. CONCLUSIONS: Younger women and women undergoing treatment at large hospitals are more likely to receive the breast-conserving P + R. Black women treated in small hospitals appear to be particularly unlikely to receive P + R. PMID- 1739147 TI - Breast cancer screening practices among users of county-funded health centers vs women in the entire community. AB - BACKGROUND: Breast cancer screening rates tend to be lower among women with lower income and/or education. METHODS: Telephone surveys of random samples of women aged 50 to 75 who had visited five health centers (n = 795) and women in the same age group residing in the entire community (n = 404) were conducted in 1988. RESULTS: Despite the significantly lower socioeconomic level, a higher proportion of minority women, and a poorer knowledge of mammography, screening rates in the health center group were not lower than in the community sample. About half or more of the health center respondents had ever had a mammogram regardless of income, education, age, and ethnic group. Of the community respondents, 49% had ever had a mammogram, but the proportion varied significantly by income and education. Within the subgroup of women having annual incomes below $15,000, mammography use was actually higher among health center women; that is, 50% of health center vs 35% of community women reported ever having a mammogram and 31% vs 14%, respectively, reported having a mammogram in the past year. CONCLUSION: The findings demonstrate the importance of publicly funded health centers in achieving screening rates among the socioeconomically disadvantaged that are comparable to (or even higher than) those in the general population. PMID- 1739149 TI - Vaginal douching among women of reproductive age in the United States: 1988. AB - BACKGROUND: Vaginal douching has been associated with pelvic inflammatory disease (PID) in several epidemiologic studies. METHODS: To determine the extent to which douching is practiced and to describe the population subgroups in which it is most prevalent, we analyzed data from the 1988 National Survey of Family Growth, which is based on a nationally representative sample of 8450 United States women between the ages of 15 and 44 years. RESULTS: Thirty-seven percent of the sample reported douching; 18% douched at least once a week. The variable most strongly and consistently associated with douching was race: two thirds of Black women, but only one third of White women, reported douching. The practice was least frequent among 15- to 19-year-olds (31%) and most frequent among 20- to 24-year olds (41%). Douching was more common among women who lived in poverty (50%) than among those who did not (28%). Seventy percent of Black women living in poverty reported douching. Women with less than a high school education were almost four times more likely to report douching as those with 16 or more years of schooling (56% vs 16%). Women with only 1 partner and those with 10 or more partners were less likely to douche than others. Sixteen percent of women who reported douching, compared with 10% of those who did not, also reported a history of PID. CONCLUSIONS: Douching may be a modifiable risk factor for PID, it should be a high priority for future etiologic research. PMID- 1739148 TI - Geographic and socioeconomic variation in the onset of decline of coronary heart disease mortality in white women. AB - BACKGROUND: Regional, metropolitan, and socioeconomic factors related to the onset of decline of coronary heart disease (CHD) mortality among White women are reported. Such studies are important for planning population-level interventions. METHODS: Mortality data for 1962 to 1978 were used, to estimate the year of onset of decline. Ecological analyses of socioeconomic data from the US census were used to emphasize structural and organizational aspects of changes in disease, rather than as a substitute for an individual-level design. RESULTS: Onset of decline of CHD mortality among White women was estimated to have occurred by 1962 in 53% of 507 state economic areas (SEAs), ranging from 79% in the Northeast to 39% in the South. Metropolitan areas experienced earlier onset of decline than did nonmetropolitan areas. Average income, education, and occupational levels were highest in early onset areas and declined across onset categories. CONCLUSIONS: The results provide additional evidence for previously observed geographic and social patterns of CHD decline. Emphasis on structural economic factors determining the shape of the CHD epidemic curve does not detract from the medical importance of risk factors, but underscores the importance of community development to public health improvements. The results are consistent with the idea that the course of the CHD epidemic in the United States has been strongly influenced by socioeconomic development. PMID- 1739150 TI - Employment status and heart disease risk factors in middle-aged women: the Rancho Bernardo Study. AB - BACKGROUND: In recent years, an increasing number of women have been entering the labor force. It is known that in men, employment is related to heart disease risk, but there are few studies examining this association among women. METHODS: The relation between employment status and heart disease risk factors including lipid and lipoprotein levels, systolic and diastolic blood pressure, fasting and postchallenge plasma glucose and insulin levels, was examined in 242 women aged 40 to 59 years, who were participants in the Rancho Bernardo Heart and Chronic Disease Survey. At the time of a follow-up clinic visit between 1984 and 1987, 46.7% were employed, primarily in managerial positions. RESULTS: Employed women smoked fewer cigarettes, drank less alcohol, and exercised more than unemployed women, but these differences were not statistically significant. After adjustment for covariates, employed women had significantly lower total cholesterol and fasting plasma glucose levels than unemployed women. Differences on other biological variables, although not statistically significant, also favored the employed women. CONCLUSIONS: Results of this study suggest that middle-aged women employed in managerial positions are healthier than unemployed women. PMID- 1739151 TI - AIDS in bisexual men in the United States: epidemiology and transmission to women. AB - BACKGROUND: Homosexual and bisexual men with acquired immunodeficiency syndrome (AIDS) differ, and bisexual men play an important role in the sexual transmission of human immunodeficiency virus (HIV) to women. METHODS: To describe AIDS in these groups, we examined AIDS cases reported nationally through June 1990. RESULTS: Among 65 389 men who reported having had sex with men since 1977, 26% were bisexual. More Black (41%) and Hispanic men (31%) than White men (21%) reported bisexual behavior. Bisexual men were twice as likely to report intravenous drug use (20%) as were homosexual men (9%), regardless of race or ethnicity. Among 3555 women with heterosexually acquired AIDS, 11% reported sexual contact with a bisexual man and no other risk factor, although in some states approximately half reported such contact. In 1989, the AIDS rate due to sex with a bisexual man was three and five times higher among Hispanic and Black women, respectively, than among White women. CONCLUSIONS: Differences between bisexual and homosexual men with AIDS and the relative importance of AIDS in women due to sexual contact with bisexual men should be considered in the development of HIV prevention programs. PMID- 1739152 TI - Knowledge and attitudes about AIDS among corporate and public service employees. AB - BACKGROUND: We examined the relationship between workplace AIDS education efforts and workers' knowledge about HIV transmission and their attitudes toward coworkers with AIDS. METHODS: Questionnaires were mailed to corporate and public service workers at 12 work sites to ascertain the extent of their knowledge about AIDS and their attitudes toward coworkers with AIDS. Each work site had offered an AIDS education program. The average response rate was 40%; 3460 workers returned questionnaires. RESULTS: Respondents' knowledge was largely consistent with available scientific evidence. However, a substantial minority still believe HIV infection can be transmitted through casual contact. Over 30% endorse the screening of new employees for AIDS, and 23% would fear contagion from an infected coworker. Thirty percent of the respondents expressed skepticism about the veracity of information from government sources and the scientific community. Work site comparisons show that where educational programs are minimal, employees know less about HIV transmission and hold more negative attitudes. CONCLUSION: Comprehensive workplace AIDS education programs can reinforce workers' knowledge about HIV transmission, thereby fostering more favorable views toward coworkers with AIDS. PMID- 1739153 TI - Workplace compliance with a no-smoking law: a randomized community intervention trial. AB - BACKGROUND: Compliance with state and local laws restricting smoking in public places and workplaces has not been systematically evaluated. METHODS: We assessed workplace compliance with a comprehensive no-smoking law adopted in Brookline, Mass, and tested whether mailing information to businesses increased awareness of and compliance with the law. We conducted a random sample telephone survey of 299 businesses (87% response rate). Self-reported compliance was validated by direct observations. RESULTS: One year after its adoption, the law was popular with businesses. The prevalence of smoking restrictions, smoking policies, and no smoking signs was 80%, 59%, and 40%, respectively. One third of businesses banned smoking. Full compliance with the law was low, however, because few businesses posted a copy of their smoking policy as required. The mailing increased employers' awareness of the law. Employers sent the mailing also reported better compliance, but this was not confirmed by direct observations. CONCLUSIONS: The law was popular and contributed to a high prevalence of workplace smoking restrictions. Different interpretations of the law by policymakers and businesses seemed to explain why formal compliance was low. The mailing increased awareness of, but not compliance with, the law. PMID- 1739154 TI - Attitudes toward genetic testing of Amish, Mennonite, and Hutterite families with cystic fibrosis. AB - BACKGROUND: We had the unique opportunity to study families with cystic fibrosis (CF) from an interrelated Amish-Mennonite kindred and from an isolated Hutterite kindred. METHODS: While obtaining blood for DNA linkage analysis to help find the CF gene, we asked family members to answer a questionnaire about attitudes and feelings toward genetic testing. The questionnaire was also administered to families receiving care at the University of Rochester. After DNA-based CF carrier testing was developed, we asked the families whether they wanted to know the results. RESULTS: Each cultural group felt differently about many issues. Between 31% and 78% approved of CF-carrier testing and 14% to 78% approved of prenatal diagnosis. The majority (59%) of Hutterite parents and siblings were opposed to carriers marrying carriers and most (82%) of the CF families wanted to know the results of carrier testing. CONCLUSIONS: Cultural differences need to be understood before genetic services are offered. Also, most CF mutations and their clinical correlates (phenotypes) will need to be defined. There are as few as three CF mutations in the Hutterite population. It will be possible to offer them the option to choose accurate genetic counseling. It will be difficult to offer genetic services to other populations with more heterogeneous attitudes and many more identified and yet-to-be-identified CF mutations. PMID- 1739155 TI - The accuracy of Medicare's hospital claims data: progress has been made, but problems remain. AB - BACKGROUND: Health care databases provide a widely used source of data for health care research, but their accuracy remains uncertain. We analyzed data from the 1985 National DRG Validation Study, which carefully reabstracted and reassigned ICD-9-CM diagnosis and procedure codes from a national sample of 7050 medical records, to determine whether coding accuracy had improved since the Institute of Medicine studies of the 1970s and to assess the current coding accuracy of specific diagnoses and procedures. METHODS: We defined agreement as the proportion of all reabstracted records that had the same principal diagnosis or procedure coded on both the original (hospital) record and on the reabstracted record. We also evaluated coding accuracy in 1985 using the concepts of diagnostic test evaluation. RESULTS: Overall, the percentage of agreement between the principal diagnosis on the reabstracted record and the original hospital record, when analyzed at the third digit, improved from 73.2% in 1977 to 78.2% in 1985. However, analysis of the 1985 data demonstrated that the accuracy of diagnosis and procedure coding varies substantially across conditions. CONCLUSIONS: Although some diagnoses and all major surgical procedures that we examined were accurately coded, the variability in the accuracy of diagnosis coding poses a problem that must be overcome if claims-based research is to achieve its full potential. PMID- 1739156 TI - Cancer anxiety and attitudes toward mammography among screening attenders, nonattenders, and women never invited. AB - A mailed questionnaire survey was conducted among the following groups: 179 women who screened false positive at a free mammography screening; a random sample of 250 women who screened negative; 670 nonattenders of the screening; and a random population sample of 250 women who lived in another city and were not invited, but were otherwise comparable. The most frequently reported reason for nonattendance was not having the opportunity. Furthermore, only 18% of the nonattenders reported anxiety about breast cancer compared with 33% of the population sample (P less than .05). Ninety-nine percent of the women who attended indicated a positive attitude toward mammography that had not been adversely affected by screening experiences. PMID- 1739157 TI - Medicaid coverage of screening tests for breast and cervical cancer. AB - Although most women receive periodic Papanicolaou smear (Pap) those who do not are more likely to be of lower socioeconomic status. Similarly, for the many women who do not receive periodic mammography for early diagnosis of breast cancer, cost has often been cited as a reason. Medicaid provides health benefits to roughly 9.4 million women of the appropriate ages for Pap tests and roughly 3.3 million women of the appropriate ages for mammography. The decision to provide such coverage is made on the state level. Of the 50 states and the District of Columbia, 49 provide some level of coverage for Pap smears, 39 for screening mammography. Knowing the extent of coverage allows public health professionals to take advantage of this funding source to provide services for lower-income women and may help initiate coverage in those states where it is not currently available. PMID- 1739158 TI - Distribution of HIV type 1 infection in childbearing women in California. AB - The incidence of acquired immunodeficiency syndrome (AIDS) is increasing among California heterosexuals and children. To assess human immunodeficiency virus (HIV)-1 infection in childbearing women, we conducted a blinded serosurvey of newborns. Dried blood specimens taken from 99% of California births during the third quarter of 1988 (n = 135,808) and linked only to maternal demographic categories were tested for HIV-1 antibody by enzyme immunoassay and confirmed by Western blot. Period prevalence of HIV-1 infection was 7.4 per 10,000 childbearing women. Prevalence was highest for Black women and was also elevated for Hispanic and San Francisco Bay Area women. Findings suggest that California Hispanic women will make up an increasing proportion of new AIDS cases. PMID- 1739159 TI - Cesarean section rates in Italy by hospital payment mode: an analysis based on birth certificates. AB - The study, based on birth certificate data from 1985 through 1987, investigated cesarean section (CS) rates in the Lazio region of Italy and their relationship with mode of hospital care payment. Use of abdominal delivery increased from 22.3% in 1985 to 24.3% in 1987. CS rates were highest (34.7%) in private hospitals. A marked variation in the use of CS was associated with mode of hospital care payment independently from other predictors of abdominal delivery. PMID- 1739160 TI - Professional relationships between midwives and physicians: collaboration or conflict? AB - This study examines the professional relationships between midwives and physicians providing obstetrical care in Washington State. Four hundred ninety six randomly sampled family physicians and obstetrician-gynecologists and 211 certified nurse, licensed, and lay midwives were surveyed to learn more about midwife/physician consulting relationships. Only certified nurse midwives have forged mutually satisfactory relationships with the physician community. Increased hospital-based training and practice opportunities are needed before licensed midwives can improve their professional relationships with physicians. PMID- 1739161 TI - Factors associated with artificial feeding in Shanghai. AB - Factors associated with artificial feeding were analyzed for 3285 infants in Shanghai. Boys, those from more highly educated families, and those born by assisted delivery or by cesarean section were more likely to be artificially fed than were girls, those from less educated families, and those born by spontaneous delivery. Infants whose birth weight was around 3750 g had the lowest probability of artificial feeding; higher and lower birth weights were positively associated with artificial feeding. PMID- 1739162 TI - Smoking-related behavior, beliefs, and social environment of young black women in subsidized public housing in Chicago. AB - Survey data indicate that young Black female smokers living in public housing are heavier smokers and have weaker motivation to quit, health beliefs and social environment less conducive to cessation, and less knowledge of where to get help to quit than other young Black female smokers in metropolitan Chicago. Compared with White women, the latter, other Black women smoke fewer cigarettes daily and have a stronger desire to quit and more concern about health reasons for quitting, but have a weaker belief in the risk of lung cancer from smoking, greater concern about quitting difficulties, and less knowledge of where to get help to quit. Low education, not race, is associated with higher smoking prevalence and less social pressure to quit or support for quitting. PMID- 1739163 TI - Smoking initiation and cessation in relation to body fat distribution based on data from a study of Swedish women. AB - In a representative sample of Swedish women, smokers were significantly less obese than nonsmokers. However, a smoker was likely to have significantly more upper-body fat than a nonsmoker of similar body mass index. Women who quit smoking experienced less upper-body fat deposition than would be expected by their accompanying weight gain, suggesting that weight gained as a consequence of smoking cessation is not preferentially deposited in the region associated with increased cardiovascular risk. PMID- 1739164 TI - Surveillance of occupational lead exposure in New Jersey: 1986 to 1989. AB - Between January 1986 and June 1989, 1916 New Jersey workers were identified through a surveillance system for occupational lead exposure. The average annual proportion of workers with a blood lead level above 2.42 mumol/L was 12%. Industries with the highest proportion of workers with blood lead levels above 2.42 mumol/L were special trade construction (35%) and industries dealing with scrap and waste materials (27%). PMID- 1739165 TI - Inaccuracies in certification of nonmelanoma skin cancer deaths. AB - Nonmelanoma skin cancer is the most common cancer site in the United States, yet mortality from this cause is poorly understood. We sought medical records of the 16 reported deaths during 1979 through 1987 from this cause (International Classification of Diseases, 9th version [ICD-9], code 173) among Rhode Island residents to evaluate the accuracy of the reported cause of death. Of the 110 cases for which the cause of death could be classified as correct or incorrect, 59 (54%) were misclassified, 49 (83%) of which were mucous-membrane, squamous cell carcinomas of the head and neck. For most of these, the written death certificate diagnosis was squamous-cell carcinoma of the head and neck, which was coded 173.4. Other problematic diagnoses were cancer of the head and neck and malignant fibrous histiocytoma. In response to a mailed survey, most health departments replied that squamous-cell carcinoma of the head and neck was coded under rubric 173 and malignant fibrous histiocytoma was coded under rubric 171, but there was no unanimity. The misclassification of other causes of death to ICD 9 rubric 173 is substantial. The vast majority were coded to rubric 173.4 and were due to a small number of diagnoses that are recognizable on examination of the death certificate. PMID- 1739166 TI - Provider compliance with recommended dietary fluoride supplement protocol. AB - Proper dosage of dietary fluoride supplements is important for children without access to optimally fluoridated water to balance dental caries prevention and risks of dental fluorosis. Subsequent to water fluoride assay, compliance by physicians and dentists with the recommended dietary fluoride supplement dosage schedule was determined for 446 children. Approximately one third of child patients and 42% of siblings did not receive the recommended supplement dosage. PMID- 1739167 TI - Condom use in multi-ethnic neighborhoods of San Francisco: the population-based AMEN (AIDS in Multi-Ethnic Neighborhoods) Study. AB - We examined the prevalence and correlates of condom use in a community-based sample of unmarried heterosexual and gay/bisexual Whites, Blacks, and Hispanics (aged 20 to 44 years) in San Francisco (n = 1229). Only 9% of heterosexual males reported always using condoms, and fewer of those with multiple sexual partners (6%) reported always using condoms compared with those in monogamous relationships (12%). Much higher proportions of gay/bisexual men reported always using condoms (48%). Racial differences in condom use were observed only among women. Sexual communication and the sexual enjoyment value of condoms were consistent correlates of condom use across gender and sexual orientation, while other condom-related beliefs were significant predictors of condom use only for men. In general, condom promotion programs should build sexual communication skills, teach people how to enhance enjoyment with condoms, and reduce psychological barriers to condom acquisition and use. PMID- 1739168 TI - Women healers of the middle ages: selected aspects of their history. AB - The stellar role of women as healers during the Middle Ages has received some attention from medical historians but remains little known or appreciated. In the three centuries preceding the Renaissance, this role was heightened by two roughly parallel developments. The first was the evolution of European universities and their professional schools that, for the most part, systematically excluded women as students, thereby creating a legal male monopoly of the practice of medicine. Ineligible as healers, women waged a lengthy battle to maintain their right to care for the sick and injured. The 1322 case of Jacqueline Felicie, one of many healers charged with illegally practicing medicine, raises serious questions about the motives of male physicians in discrediting these women as incompetent and dangerous. The second development was the campaign--promoted by the church and supported by both clerical and civil authorities--to brand women healers as witches. Perhaps the church perceived these women, with their special, often esoteric, healing skills, as a threat to its supremacy in the lives of its parishioners. The result was the brutal persecution of unknown numbers of mostly peasant women. PMID- 1739169 TI - Mum's the word: the Supreme Court and family planning. AB - On May 23, 1991, the US Supreme Court upheld federal regulations that prohibit federally funded family planning programs from counseling about or referring for abortion. As a result, government benefits may now entail substantial costs. The regulations changed the nature of government-assisted family planning from comprehensive care and counseling to limited services and government-prescribed information. The reasoning in Rust v Sullivan allows government to limit freedom of speech in federally funded programs. The decision may have been influenced by antiabortion sentiment, but it does not affect the legality of abortion. Instead, it sets a precedent for government control of whether and how health care can be discussed wherever government pays some of the bills. PMID- 1739170 TI - Mammography outreach program. PMID- 1739171 TI - A statewide early intervention program for HIV-infected people. PMID- 1739172 TI - A randomized prospective clinical trial to determine the efficacy of interferon gamma in severely injured patients. AB - Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted. Two hundred thirteen trauma patients who were at high risk of infection received either placebo or rIFN-gamma (100 micrograms) subcutaneously each day for 10 days after admission. One hundred ninety-three patients were evaluable with respect to primary end points. Patients treated with rIFN-gamma were older (p = 0.10) and had more severe modes of injury (p = 0.02). By the third day, both monocyte HLA-DR antigen expression and outcome predictive score were significantly better in the rIFN-gamma-treated group than in the placebo group (p = 0.0001 and p = 0.0006, respectively). Nine deaths occurred in patients treated with rIFN-gamma compared with 12 deaths in the placebo group (p = 0.46). Major infections requiring surgical drainage or debridement occurred in 17 patients treated with rIFN-gamma compared with 22 treated with placebo. No difference between treatment arms was noted in overall major or minor infection rates, but there were fewer severe infections that required reoperation or computer tomographic-guided drainage in patients receiving IFN-gamma. While these results suggest that rIFN-gamma may be useful in some aspects of infection in the patient with severe trauma, a larger trial with longer treatment will be needed to prove the comprehensive value of rIFN-gamma. PMID- 1739173 TI - Pelvic abscess or pseudoaneurysm: diagnostic and therapeutic dilemma following iliac arterial trauma. AB - Intra-abdominal abscesses often complicate operations for abdominal trauma and are particularly dangerous in patients whose injuries involve major vessels. We report our experience with 10 patients who developed pelvic abscesses among 75 survivors of iliac arterial injuries. Pseudoaneurysms of primarily repaired iliac arteries occurred in 8 of these 10 patients. Emergency operations were required for acute arterial thrombosis or hemorrhage in four patients; massive hemorrhage that complicated the drainage of pelvic abscesses led to the recognition of the pseudoaneurysms in the other four patients. Three of the eight patients with pseudoaneurysm died of postoperative complications; ischemic extremity sequelae occurred in all five survivors. The association of pelvic abscesses with the complications iliac arterial repairs has not been previously emphasized. The integrity of an arterial repair should be arteriographically confirmed before proceeding with drainage of a pelvic abscess that developed after iliac arterial trauma. PMID- 1739174 TI - Augmentation of the immune response of the murine liver by levamisole. AB - Murine hepatic nonparenchymal cells (NPC) were studied following in vivo treatment with levamisole. This agent was found to increase the cytolytic action of these cells against YAC-1 and P815 target cells. An increase in the cytostatic activity against liver-derived murine colon adenocarcinoma 38 tumor cells was also observed. Treatment with levamisole also augmented the proliferation of the hepatic NPC. Supernatants generated by these cells contained an agent capable of stimulating the proliferation of bone marrow cells from the same mice. The effect of levamisole on different subsets of NPC derived from the liver in this model is discussed. PMID- 1739175 TI - Postprandial augmentation of portal hepatic inflow after prosthetic H-graft portacaval shunt. AB - Encephalopathy after portasystemic shunting generally occurs after eating. After partial portal decompression, encephalopathy is uncommon, presumably because of associated portal hemodynamics. However, after partial shunting, the changes in portal venous hemodynamics that occur with eating are unknown. With this in mind, 11 nonencephalopathic adults were studied more than 1 year after 8-mm H-graft portacaval shunt (PCS). The studies utilized color flow duplex ultrasound to determine the changes in portal vein (PV) and inferior vena cava blood flow that occur with eating a standardized meal. Following H-graft PCS, there is increased blood flow in the inferior vena cava after eating, particularly cephalad to the H graft PCS, implying increased flow through the prosthetic shunt. Eating also increases hepatopedal blood flow in the PV distal to the H-graft PCS. Postprandial increases in hepatopedal portal blood flow may play an important role in avoiding encephalopathy after H-graft PCS. PMID- 1739176 TI - Internal pancreatic fistula. AB - Internal pancreatic fistulae are well-recognized complications of inflammatory pancreatic disease. From 1963 to 1990, 50 patients with either pancreatic ascites (34), pancreatic ascites and pleural effusion (7), or pancreatic pleural effusion (9) were treated. Initial therapy was conservative, consisting of gastrointestinal rest, serosal apposition with paracentesis or thoracentesis, with or without the administration of anti-secretagogues. This therapy was successful in 21 of 42 patients, but 5 deaths occurred. Operative therapy was performed in 24 patients. There was one surgical failure and two deaths early in the experience. Ten of our final 16 patients underwent liver biopsy, and all 10 were found to have cirrhosis. All patients, even those with documented cirrhosis, should have routine amylase and albumin determinations on ascitic or pleural fluid. Internal pancreatic fistulae should be treated initially nonoperatively; if this is ineffective, operative therapy has an acceptably low morbidity and mortality. PMID- 1739177 TI - Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration. AB - Thirty-four patients with suspected common bile duct stones were randomized to undergo endoscopic cholangiography and stone removal prior to open cholecystectomy or to have open cholecystectomy, operative cholangiography, and common bile duct exploration. Sixteen underwent the first protocol, and 18 the second. Analysis of the ability to clear stones from the common bile duct, morbidity, mortality, hospital stay, length of operation, and hospital cost showed no difference in outcome between patients treated by either method. These data suggest there is neither an advantage nor a disadvantage to treating patients with suspected duct stones by precholecystectomy endoscopic cholangiography and stone removal. PMID- 1739178 TI - Improvement in survival of mice with proximal small bowel obstruction treated with octreotide. AB - Small bowel obstruction is a common disorder in surgical practice. The major morbidity of bowel obstruction relates to intestinal distension and ischemia. We hypothesized that octreotide, a potent inhibitor of gut secretion, would reduce mortality in a mouse model of lethal small bowel obstruction. C57 mice were anesthetized with urethane and prepared with either proximal jejunal or distal ileal obstruction. After 8 hours, surviving mice were randomized to receive either octreotide (100 micrograms/kg) or saline subcutaneously every 8 hours. Octreotide significantly improved survival in mice with proximal obstruction by life table analysis. Mean survival increased from 31 +/- 3 to 41 +/- 4 hours. In distal obstruction, octreotide treatment resulted in a trend towards improved survival; however, this trend failed to reach statistical significance by life table analysis. The improvement in survival in this mouse model suggests that octreotide may be a valuable adjunct in the treatment of patients with small bowel obstruction. PMID- 1739179 TI - Comparative efficacy of topical hemostatic agents in a rat kidney model. AB - The efficacies of four topical hemostatic agents were compared in a rat model employing a standardized renal injury. The materials used to effect hemostasis were oxidized cellulose, microfibrillar collagen powder, positively charged modified collagen, and single donor heterologous fibrin glue. Animals that were treated only with surgical gauze served as controls. Hemostasis was achieved by application of one of the topical hemostatic agents plus moderate digital pressure. The time necessary to achieve complete hemostasis was recorded for each animal. Control animals bled profusely and suffered an increased postoperative mortality rate compared with the experimental animals. Microscopic studies demonstrated progressive healing of the injuries with varying degrees of inflammation and scar formation. Fibrin glue was by far the most effective agent in controlling hemostasis. The collagen materials, though effective, required a longer time to control bleeding and did not differ statistically in their activity from one another. PMID- 1739180 TI - Surgical treatment of primary carcinoma of the gallbladder based on the histologic analysis of 48 surgical specimens. AB - During the past 5 years, extended cholecystectomy and/or more radical procedures, including pancreatoduodenectomy and extended hepatic lobectomy, were performed on 48 patients with carcinoma of the gallbladder in an attempt to cure the disease. It was retrospectively proven from microscopic analysis of the surgical specimens taken from the 48 patients that 28 patients had received curative resections. The 28 consisted of all 4 patients with stage I carcinoma, all 9 with stage II, 6 of 8 with stage III, and 9 of 27 with stage IV. We reached the following conclusions: (1) extended cholecystectomy with resection of the bile duct in the hepatoduodenal ligament is the optimum procedure for patients with stage I and stage II carcinomas, and (2) for patients with stage III carcinoma, more radical procedures, including pancreatoduodenectomy and/or wider resection of the liver, might result in curative resection of the disease. For some patients with stage IV tumors, such as duodenal invasion or direct invasion of the liver, curative resection may be achieved by pancreatoduodenectomy or extended hepatic lobectomy. PMID- 1739181 TI - Hepatic resections for primary and metastatic tumors using the ultrasonic surgical dissector. AB - We have previously described the development of new hepatic surgical techniques using the ultrasonic surgical dissector. With 10 years' experience, we have found that major liver resections have been simplified and that the technique is repeatable in hands other than our own. Thirty-three patients had 37 tumors, averaging 5.65 cm in size, resected with an average blood loss of only 1,020 mL per case, which included 5 right trisegmentectomies, 12 lobectomies, 15 segmental resections, and 4 subsegmental resections. Twenty-two patients had metastatic colorectal cancer. Blood transfusion requirements averaged only 2.24 units in long-term survivors, which was significantly less than the 3.5 units received by patients who have since died (p = 0.092). There were no operative deaths. The median survival of these 22 patients was 56 months, and the 5-year actuarial survival rate was 35%. All of the early deaths occurred in patients with more than four tumors, and no patient with less than four tumors died before 42 months with recurrent disease. Six patients had bilateral tumors, and the fact that patients survived into the fourth and fifth post-resectional year indicates that resection was worthwhile. All these patients had Dukes' C primary tumors, but we found no statistical difference in survival between patients with Dukes' B and Dukes' C lesions. The results indicate that hepatic resection with the ultrasonic surgical dissector decreases blood loss, requires few transfusions, is safe to perform, and is associated with excellent long-term survival. PMID- 1739182 TI - Can general surgeons perform colonoscopy safely? AB - The purpose of the current study was to review the safety of colonoscopy performed by nonfellowship-trained general surgeons. To address this issue, we reviewed more than 1,000 consecutive diagnostic and therapeutic colonoscopies and recorded the complications. This was a multi-institutional study involving seven general surgeons, none of whom had had formal fellowship endoscopic training. Perforation was confirmed by laparotomy, bleeding was defined as that requiring hospitalization and/or transfusion, and cardiopulmonary arrest was self explanatory. There was one perforation in the diagnostic group and none in the therapeutic group, for a rate of 0.10% overall and 0.12% in diagnostic colonoscopy. There were no instances of bleeding or cardiac arrest. This complication rate of 1 per 1,025 colonoscopic procedures by general surgeons compares favorably with that previously reported by other specialties (p less than 0.001). We conclude that postgraduate endoscopy fellowship is not necessary for general surgeons to become safe colonoscopists. PMID- 1739183 TI - Biliary tract reconstruction after injury of the main hepatic duct. PMID- 1739184 TI - Risks of precut papillotomy and the management of patients with duodenal perforation. PMID- 1739185 TI - Intra-abdominal procedures in pregnant women. PMID- 1739186 TI - Management of exercise-induced asthma. PMID- 1739187 TI - Asthma during pregnancy: interrelationships and management. PMID- 1739188 TI - Adverse reactions to cocaine. PMID- 1739189 TI - Cat scratch disease and nontuberculous mycobacterial disease: diagnostic usefulness of PPD-Battey, PPD-T and cat scratch skin test antigens. PMID- 1739190 TI - Forced oscillation technique. Reference values for total respiratory resistance obtained with the Siemens Siregnost FD5. AB - Total respiratory resistance (Rrs) was measured by the application of a sine wave of airflow to the mouth at an oscillation frequency of 10 Hz. The instrument used was the Siemens Siregnost FD5. The Rrs data were correlated with height, age, sex, and weight in 73 patients and 29 healthy subjects. The patients took part in a rehabilitation program for restoration of their locomotion function. Both groups had normal lung function (VC, FEV1) and no signs of pulmonary disease. The only important determining factor for the value of the Rrs was height. The mean Rrs of 102 subjects was 0.29 +/- 0.08 kPa.1-1.s. Other studies gave values between 0.23 +/- 0.05 and 0.32 +/- 0.10 kPa.1-1.s. PMID- 1739191 TI - Superficial nasal mucosal blood flow and nasal patency following topical oxymetazoline hydrochloride. AB - The objective of this study was to evaluate the effect of 60 micrograms oxymetazoline on nasal mucosal blood flow (NMBF) measured by laser Doppler velocimetry. Nasal airflow (measured by anterior rhinomanometry) and subjectively perceived airflow (measured by visual analog scales) were also evaluated. A reduction of NMBF (mL/100 g tissue/min) was observed following local application of 60 micrograms oxymetazoline that was not observed after the vehicle was applied. For example, NMBF at baseline was measured at 78.8 +/- 10.3 mL/100 g tissue/min (mean +/- SEM). During the five minutes following vehicle application, mean values remained at 81.8 +/- 8.8 mL/100 g tissue/min. Five minutes after topical oxymetazoline treatment, NMBF was reduced 49% to 38.3 +/- 10.2 mL/100 g tissue/min. Nasal airflow (mL/sec), which was measured before and after LDV probe placement, was not significantly increased in either the ipsilateral (281.4 +/- 33.1 to 314.3 +/- 31.6) or contralateral nostril (335.7 +/- 26.9 to 262.1 +/- 36.4), probably due to the limited surface application of drug. Subjective assessments of congestion by both the investigator and the subject showed significant improvements in the ipsilateral nostril. We conclude that, under the conditions of our study, localized application of 60 micrograms oxymetazoline significantly reduces superficial nasal blood flow and provides subjectively perceived improvements in nasal stuffiness. PMID- 1739192 TI - Evaluation of a generic albuterol metered-dose inhaler: importance of priming the MDI. AB - Since the patent on albuterol metered-dose inhalers (MDI) expired in 1989, several manufacturers have developed generic products. In order to determine whether one generic albuterol MDI is equivalent to a reference product (Ventolin MDI), we compared the relative efficacy of two puffs (180 micrograms) of each inhaler in 17 intermittent or mild chronic adult asthmatics (FEV1 48% to 77% predicted) in a randomized, single-blind, crossover manner. The test dose was the first two puffs out of each canister. Pulmonary function was measured before each test dose and at frequent intervals over eight hours. Baseline FEV1 values on both study days were within 20%. The mean +/- SD peak effect was 80.5 +/- 15.5% of maximum achievable improvement in FEV1 after the generic compared with 92.2 +/ 8.8% after Ventolin (P = .006). The area under the curve (AUC) for this same measurement during the first four hours was 242 +/- 75%.hr-1 after the generic compared with 297 +/- 40%.hr-1 after Ventolin, a mean difference of 19% (P = .002). The study was then repeated with the MDI primed prior to the test dose (ie, two puffs were first discharged into a waste basket) in subjects willing to return for re-study (n = 11). There was no significant difference in AUC in the second study: 215 +/- 77%.hr-1 after generic and 228 +/- 82%.hr-1 after Ventolin (P = .65); however, there was only a 35% chance of detecting a 20% difference in AUC with this sample size. These data indicate that, without priming, an MDI may deliver less drug, and thereby less therapeutic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739193 TI - Combined effect of nifedipine and diltiazem on methacholine-induced bronchoconstriction in asthmatic patients. AB - Calcium blockers alter airway hyperreactivity. We studied the effect of either 60 mg diltiazem or 20 mg nifedipine and their combination on the airway response to methacholine-induced bronchoconstriction. Compared with placebo or diltiazem, nifedipine significantly raised the PC20. When diltiazem was given alone, it had no effect on the airway but, when given with nifedipine, it significantly raised the PC20 to methacholine. The effect was superior to any of the other treatments given. This study supports the concept of combining two different calcium blockers in the treatment of bronchial asthma. PMID- 1739194 TI - Increasing asthma mortality in Denmark 1969-88 not a result of a changed coding practice. AB - We have studied asthma mortality in Denmark from 1969 to 1988. Age standardized mortality rates calculated in three age groups, 10-34, 35-59, and greater than or equal to 60 years, disclosed similar trends. Increasing mortality from asthma in the mid-1970s to 1988 was seen in all three age groups with higher mortality in 1979-88 as compared with 1969-78 of 95%, 55%, and 69%, respectively. Since the eighth revision of the International Classification of Diseases (ICD8) was used in Denmark over the entire 20-year period, changes in coding practice due to change of classification system cannot explain the findings. PMID- 1739195 TI - Hemorrhagic infarct conversion in experimental stroke. AB - STUDY OBJECTIVE: This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion. DESIGN: Prospective, controlled laboratory investigation. TYPE OF PARTICIPANTS: One hundred six pentobarbital anesthetized cats. INTERVENTIONS: The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion. MEASUREMENTS AND MAIN RESULTS: Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage. CONCLUSION: Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation. PMID- 1739196 TI - Plasma catecholamine levels after intraosseous epinephrine administration in a cardiac arrest model. AB - STUDY OBJECTIVE: To measure plasma catecholamine levels and the cardiovascular response after administering epinephrine by the intraosseous (IO) route in an animal cardiac arrest model. MODEL: Eighteen anesthetized swine (weight, 12 to 15 kg) subjected to five minutes of electrically induced ventricular fibrillation followed by 25 minutes of chest compression and ventilation. INTERVENTIONS: Animals were anesthetized with 30 mg/kg IM ketamine and 75 mg/kg IV a-chloralose, intubated, placed on a respirator, and surgically instrumented. Ventricular fibrillation was induced. After five minutes of cardiac arrest, mechanical chest compressions were initiated and continued until the end of the experiment. Animals received 0.01 mg/kg IO epinephrine (five) or 0.1 mg/kg IO epinephrine (five) at ten and 20 minutes. The eight controls did not receive epinephrine. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine levels increased from 1.0 to approximately 40 to 85 ng/mL with the initiation of CPR. Epinephrine (0.01 mg/kg) increased plasma epinephrine levels to 222 +/- 72 ng/mL at 12 minutes after arrest but did not increase diastolic or mean blood pressure. Epinephrine (0.1 mg/kg) increased plasma epinephrine levels to 1,103 +/- 157 ng/mL at 12 minutes after arrest and increased diastolic and mean arterial blood pressures. CONCLUSION: IO epinephrine is rapidly transported to the central circulation but requires larger than currently recommended doses to produce a significant change in blood pressure. PMID- 1739197 TI - Failure of countershock-type pulses in vitro to adversely alter mitochondrial oxidative phosphorylation. AB - STUDY OBJECTIVE: The aim of the study was to investigate a potential mechanism of myocardial injury after DC countershock. The effect of countershock-type electrical discharges on rabbit heart mitochondrial oxygen consumption was measured in vitro using a novel respiration cell. MEASUREMENTS AND MAIN RESULTS: Mitochondria were isolated from the hearts of adult Dutch and New Zealand White rabbits. Single rectangular shocks (voltage gradients 20 to 80 V/cm; 5 ms duration) caused no significant changes in state 3 oxygen consumption in standard incubation medium. Single and multiple defibrillator shocks (critically damped sine waveform; 5 ms duration) with peak voltage gradients of 242 to 659 V/cm similarly had no significant effect on state 3 oxygen consumption. CONCLUSION: At voltage gradients similar to and greater than those causing myocardial cell injury and necrosis, electrical discharges do not directly depress mitochondrial function. Therefore, the reduction in mitochondrial oxygen consumption observed following transthoracic shocks in vivo may invoke other mechanisms (eg, intracellular calcium influx, high circulating noradrenaline, or free radical formation in the intact heart). PMID- 1739198 TI - Regional cerebral blood flow with manual internal cardiac massage versus direct mechanical ventricular assistance. AB - STUDY HYPOTHESIS: Previous studies have not discerned the best method for generating regional cerebral blood flow during internal cardiac massage. We hypothesized that regional cerebral blood flow generated by a mechanical method- direct mechanical ventricular assistance (DMVA)--would be superior to manual internal cardiac massage (MAN). STUDY POPULATION: Twelve adult Yucatan minipigs weighing more than 44 kg each were studied. METHODS: Swine were instrumented for regional cerebral blood flow measurements using tracer microspheres. After 15 minutes of ventricular fibrillation, swine were randomized to receive either MAN or DMVA. Regional cerebral blood flow was measured during normal sinus rhythm and at one minute (VF-1) and six minutes (VF-2) after initiation of circulatory support. Regional cerebral blood flow values were compared using a Wilcoxon rank sum test. RESULTS: During VF-1, there was a tendency for DMVA to produce greater regional cerebral blood flow than MAN, although these differences were not statistically significant (DMVA vs MAN as mL/min/100 g): cerebral cortex, 28 versus 11; cerebellum, 49 versus 22; midbrain, 43 versus 16; pons, 55 versus 18; medulla, 55 versus 19; and spinal cord, 33 versus 10. During VF-2, DMVA produced greater regional cerebral blood flows than were produced by MAN: cerebral cortex, 39 versus 12 (P less than .06); cerebellum, 58 versus 20 (P less than 0.5); midbrain, 50 versus 18 (P less than .05); pons, 52 versus 22 (P less than .06); medulla, 53 versus 20 (P less than .05); and spinal cord, 31 versus 12 (P less than .05). CONCLUSION: DMVA produces greater regional cerebral blood flow than is produced during MAN after 15 minutes of ventricular fibrillation. DMVA is effective at maintaining regional cerebral blood flow after a prolonged cardiac arrest. PMID- 1739199 TI - Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children. AB - STUDY OBJECTIVE: To examine the validity of a disposable, colorimetric end-tidal CO2 detector in verifying endotracheal tube (ETT) placement in infants and children. DESIGN: The detector was studied prospectively in 151 intubations. SETTING: Operating room, ICU, and emergency department of a children's hospital. PARTICIPANTS: One hundred thirty-seven children undergoing endotracheal intubation for anesthesia (52), respiratory support (76), or CPR (23). INTERVENTIONS: After endotracheal intubation, tube position was verified, the detector was attached, and readings were obtained. MEASUREMENTS AND RESULTS: The detector correctly identified tube position (trachea, 124; esophagus, four) in all 120 patients who were not in cardiac arrest (P less than .01). In the cardiac arrest setting, all six esophageal intubations were correctly identified, but two of the 17 tracheal intubations were incorrectly interpreted as esophageal intubations (P less than .01). CONCLUSION: The detector accurately identifies ETT position in children with spontaneous circulation who weigh more than 2 kg. During CPR, a positive test correctly indicates that the ETT is in the airway, but a negative result (suggesting esophageal placement) requires an alternate means of confirming ETT position. PMID- 1739200 TI - Pediatric bacterial meningitis: is prior antibiotic therapy associated with an altered clinical presentation? AB - STUDY HYPOTHESIS: The clinical features of children treated with oral antibiotics before the diagnosis of bacterial meningitis differ from those who receive no antibiotics. DESIGN: Retrospective case series. SETTING: University medical center. PARTICIPANTS: Two hundred fifty-eight children 24 months old or younger with bacterial meningitis hospitalized during a 12-year period. Eighty-three children were treated with oral antibiotics before the diagnosis of meningitis, and 175 children were not. INTERVENTIONS: None. METHODS: The emergency department chart and hospital records were reviewed for presenting demographic, historical, physical examination, and laboratory features. Clinical features of pretreated and untreated patients were compared. RESULTS: Pretreated children demonstrated less frequent temperature of 38.3 C or higher, altered mental status and a longer duration of symptoms before diagnosis, with more frequent vomiting; ear, nose, and throat infections; and physician visits in the week before detection of meningitis (P less than .05 for all comparisons). There was no difference in incidence of upper respiratory symptoms, seizures, nuchal rigidity, Kernig's and Brudzinski's signs, focal neurologic signs, mortality, and length of hospitalization between groups. CONCLUSION: Clinical features of children who have taken antibiotics before the detection of meningitis differ significantly from those who have not undergone antibiotic therapy. Physicians should be aware of these differences when evaluating young children on antibiotics for the possibility of meningitis. PMID- 1739201 TI - The relationship of poison center contact and injury in children 2 to 6 years old. AB - STUDY OBJECTIVE: To determine if children from households that call a poison center are at increased risk of nonpoisoning injury. DESIGN: A blinded and controlled telephone survey of two groups of households with children between 2 and 6 years old: case households identified by a poison center as having requested information regarding a possible poisoning in a child in this age group in 1989, and control households that did not contact the poison center. The control group was matched by telephone area code and prefix; the last four digits were chosen by random digit dialing. TYPES OF PARTICIPANTS: Children from 2 to 6 years old. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-nine households identified by the poison center and 136 control households completed the telephone interview. The number of children 2 to 6 years old in these households was 190 in the 129 poison control households and 209 in the 136 nonpoison control households. There were 45 injuries among the 190 children in the poison control group and 31 injuries among 209 children in the nonpoison control group. The annual rate of injuries per child was significantly greater in the poison control group (23.7%) than in the nonpoison control group (14.8%) (P less than .025; odds ratio, 1.6; 95% confidence interval, 1.1 to 2.4). CONCLUSION: Children 2 to 6 years old in households that contact a poison center for a possible poison exposure in a child in this age group are at increased risk of injury. PMID- 1739202 TI - Re-evaluation of the tympanic thermometer in the emergency department. AB - STUDY OBJECTIVE: A study was undertaken to re-evaluate tympanic temperatures using a commonly used portable infrared tympanic thermometer. DESIGN: Temperatures were recorded sequentially at two body sites using an electronic digital thermometer and an infrared tympanic thermometer. The tympanic thermometer was set to the core equivalency setting. SETTING: The emergency department of a Level 2 trauma center. TYPE OF PARTICIPANTS: Seventy-nine pediatric patients presenting to the ED. MEASUREMENTS AND MAIN RESULTS: Mean temperatures in the tympanic and rectal temperature groups were 38.5 +/- 1.08 C and 38.8 +/- 1.02 C, respectively (P greater than .05). The overall correlation of rectal and tympanic temperatures was 0.93 (P much less than .001). Stratifying the data by age resulted in a weakened correlation for patients 3 months of age and younger. For all strata, the sensitivity, specificity, positive predictive value, and negative predictive value of the tympanic thermometer for predicting fever were 96.6%, 100%, 100%, and 90.1%, respectively; for patients more than 3 months of age, the values were 100% in all categories. CONCLUSION: Our findings indicate that the First Temp infrared tympanic thermometer accurately detected fever in a pediatric population more than 3 months old. Results were inconclusive in patients less than 3 months old. PMID- 1739203 TI - Plasma cocaine and tetracaine levels following application of topical anesthesia in children. AB - STUDY OBJECTIVES: To measure plasma cocaine and tetracaine levels in children after standardized application of a solution of tetracaine 0.5%, epinephrine 0.05%, and cocaine 11.8% (TAC) to lacerations requiring suture repair. DESIGN: Nonrandomized, controlled trial over a five-month period. SETTING: University hospital emergency department. TYPE OF PARTICIPANTS: Stable children less than 16 years of age with uncomplicated lacerations. MEASUREMENTS AND MAIN RESULTS: Blood was obtained at either 15 or 20 minutes (early; 32) or 45 or 60 minutes (late; 45) for measurement of plasma cocaine and tetracaine levels. Analysis for cocaine and tetracaine concentrations was performed using gas chromatography-mass spectroscopy with a limit of detection for both assays of 0.5 ng/mL. Serum cocaine levels were low but measurable at both times in 75% of children. No tetracaine was measurable. Median cocaine levels were 1 ng/mL (range, 0 to 112 ng/mL) for the early group and 2 ng/mL (range, 0 to 274 ng/mL) for the late group (P = NS). Only two children had levels of more than 100 ng/mL. No significant correlation between patient or laceration characteristics and cocaine levels was detected. No significant change in heart rate or blood pressure was detected. Children who required additional local anesthesia had nonfacial lacerations and lower cocaine levels than children with facial lacerations. CONCLUSION: Application of 3 mL of standard TAC solution for 15 minutes results in low but measurable plasma cocaine levels in 75% of children. PMID- 1739204 TI - Emergency medicine & injury control. PMID- 1739205 TI - Trauma systems development. PMID- 1739206 TI - Emergency medicine, "where are ye?". PMID- 1739208 TI - Use of statistical tests. PMID- 1739207 TI - Opportunity knocks. What will we do? PMID- 1739209 TI - An academic status report for emergency medicine. PMID- 1739210 TI - The use of external, noninvasive pacing for the termination of ventricular tachycardia in the emergency department setting. AB - STUDY OBJECTIVE: To determine the potential usefulness of external cardiac pacing for the termination of sustained ventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Five men and one woman (mean age, 57 years) who presented to the ED with a wide-complex, hemodynamically stable tachycardia that was later proven to be ventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate of 200 pulses per minute. RESULTS: In all six patients, external cardiac pacing was able to successfully terminate tachycardia without complication. CONCLUSION: We conclude that external noninvasive pacing may be an effective means of terminating ventricular tachycardia in the ED setting. PMID- 1739211 TI - Pseudometabolic acidosis caused by underfill of Vacutainer tubes. AB - STUDY OBJECTIVES: To determine how serum bicarbonate and anion gap are affected by sample size in a 10-mL red-top (clot) Vacutainer tube at the fixed sample volumes of 10, 3, and 1 mL. DESIGN: Venous phlebotomy on consecutive emergency department patients; three tubes drawn in random order. The first 20 patients had unvented tubes, and the last ten had the tubes vented within one minute of the draw. SETTING: University hospital ED. PARTICIPANTS: Thirty ED patients. INTERVENTIONS: All blood samples had electrolytes determined within one hour of phlebotomy. To approximate the ED setting, the time to analysis was not controlled, but each triple draw had simultaneous analysis. MEASUREMENTS AND MAIN RESULTS: Mean bicarbonate in mmol/L (with sample size) was 21.7 (10 mL), 19.4 (3 mL), and 16.3 (1 mL) (r2 = .86, P = .0001). Anion gap in mmol/L was 16.7 (10 mL), 17.5 (3 mL), and 19.1 (1 mL) (r2 = .84, P = .0077). Venting of Vacutainer tubes did not significantly change these results. CONCLUSION: Underfill of 10-mL Vacutainer tubes causes a significant decline in bicarbonate and an increase in anion gap that may be mistaken for a metabolic acidosis. To correct for these effects, the bicarbonate should be increased by 0.5 to 0.6 mmol/L, and the anion gap should be decreased by 0.2 to 0.3 mmol/L for every milliliter of air above the sample in a 10-mL Vacutainer tube. Venting the tubes will not correct this effect. All tubes should be filled completely to avoid creating a pseudometabolic acidosis. PMID- 1739212 TI - A model research curriculum for emergency medicine. PMID- 1739213 TI - The place of emergency medicine in the academic community. PMID- 1739214 TI - Setting the national agenda for injury control in the 1990s. PMID- 1739215 TI - The antiphospholipid antibody syndrome in the emergency department setting- livedo reticularis and recurrent venous thrombosis. AB - We present the case of a 26-year-old man with an exacerbation of apparent chronic asthma with chronic peripheral vascular disease due to recurrent venous thrombosis. Localized livedo reticularis, new cutaneous infarctions, severe venous insufficiency, thrombocytopenia, renal failure, and cerebral supratentorial dysfunction were noted. During hospital admission, antibodies to phospholipids in high titer were present by three different testing methods. Renal biopsy demonstrated significant renal vasculature abnormalities characteristic of hemolytic endovasculopathy, and magnetic resonance imaging showed multiple cerebral infarctions. This case exemplifies the spectrum of presentations and management of the primary antiphospholipid antibody syndrome. The clue to its presence in this patient was the livedo reticularis rash, a cutaneous marker for this syndrome that was evident in the emergency department. PMID- 1739216 TI - The emergency management of moray eel bites. AB - As human encounters with hazardous marine life increase, emergency physicians are more frequently confronted with the management of resultant injuries. We present three cases involving hand injuries inflected by moray eels. Each was managed with local wound care and subsequent outpatient treatment with either oral ciprofloxacin or cefuroxime. One patient had mild residual hand dysfunction, and no patient developed wound infection. To better assess the bacteriology of such injuries, oral cultures were taken from captive moray eels and surrounding aquarium water. Culture and sensitivity analyses showed Vibrio and Pseudomonas to be the predominant species, both sensitive to ciprofloxacin, cefuroxime, tetracycline, and trimethoprim-sulfamethoxazole. We conclude that moray eel bites can be managed successfully with aggressive, local wound care and antibiotic coverage that targets Vibrio and Pseudomonas species. PMID- 1739217 TI - Ascariasis mimicking an acute abdomen. AB - Infection with the roundworm Ascaris lumbricoides is common in children and may mimic an acute abdomen. The cases of two pediatric patients who presented to the emergency department with signs and symptoms of a surgical abdomen are presented to highlight the presentation of this infection. Both cases were diagnosed by physical examination and radiographs and were treated successfully without surgical intervention. These cases illustrate the need for heightened awareness by the emergency physician of ascariasis in the differential diagnosis of acute abdomen. PMID- 1739218 TI - Retrograde intubation of the pharynx: an unusual complication of emergency cricothyrotomy. AB - Retrograde, translaryngeal intubation of the pharynx, a previously unreported and potentially fatal complication of emergency cricothyrotomy, is described. Methods of avoiding this complication are discussed. Reports in the literature of related technical errors following successful surgical incision of the cricothyroid membrane are discussed. PMID- 1739219 TI - Tonic status epilepticus: an unusual presentation of unresponsiveness. AB - We report an unusual cause of unresponsiveness in a 73-year-old woman seen in the emergency department. Extensive evaluation, including an emergency EEG that demonstrated rhythmic, high-voltage spike-and-wave discharges characteristic of convulsive activity, confirmed the diagnosis of generalized tonic status epilepticus. The patient's persistent subclinical seizures terminated after the IV administration of diazepam. Varying presentations of generalized tonic status epilepticus have been described in the neurology literature, with EEG confirmation of this diagnosis. Review of the emergency medicine literature does not describe a similar presentation of altered mental status in the adult population. This case illustrates one necessary role for ED EEG in the identification of occult status epilepticus causing altered mental status. PMID- 1739220 TI - Orthostatic vital signs. PMID- 1739221 TI - Pharmacotherapy of pregnancy--related SVT. PMID- 1739222 TI - Using ACE-inhibitors. PMID- 1739223 TI - The evolution of continence following total colectomy. PMID- 1739224 TI - How can general surgery survive? PMID- 1739225 TI - Acute limited normovolemic hemodilution can be safely used in a malnourished model. AB - This study investigates the effects of acute limited normovolemic hemodilution (ALNH) on intestinal healing in a malnourished animal model. Twenty rabbits were randomized into three Groups: Group 1 = control; Group 2 = ALNH (removal 35% blood volume and maintenance of normovolemia with 3:1 crystalloid infusion) followed by retransfusion (RT) after small bowel anastomosis (ANA). Group 3 had a restricted diet for 3 weeks preoperatively to cause a 15 percent to 20 percent weight loss. A six cm segment of small bowel (SB) was resected and anastomosed (ANA) in all animals. Blood pressure (BP), transserosal oxygen tension (TsPao2), hematocrit (Hct), colloid oncotic pressure (COP), wet-to-dry weight ratios (WW/DW), hydroxyproline (OH-Pro) content, and tensile strength (TS) of the ANA and a segment of adjacent SB were determined. BP did not change from baseline (BL) in Group 2 during ALNH; however, it rose significantly after RT (P less than 0.05). BP decreased significantly during ALNH in Group 3 (P less than 0.05) and did not rise above baseline after RT. There was no significant change in TsPao2 from BL within groups during the experiment. The Hct and COP decreased significantly after ALNH in Groups 2 and 3 after ALNH compared to BL (P less than 0.05). After RT the Hct and COP increased and by Day 8 the Hct had risen to BL values in Group 3 but not in Group 2 (P less than 0.05), whereas COP values were not significantly different from BL in either group. There was no difference in WW/DW or TS between or among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739226 TI - Peritoneal neutrophil chemotaxis is impaired in biliary obstruction. AB - Previous studies have shown impaired reticuloendothelial function in biliary obstruction. The chemotactic response of polymorphonuclear leukocytes from peripheral blood and peritoneal fluid of jaundiced rats (Group 1) was compared to that of sham operated controls (Group 2) and normal rats (Group 3). Male Sprague Dawley rats underwent bile duct ligation or sham celiotomy. Studies were performed from 1 to 3 weeks after surgery. Mean serum bilirubin was 6.8 mg percent in Group 1 and normal in Groups 2 and 3. Peritoneal neutrophils were induced by intraperitoneal injection of 10 ml of 10 percent peptone broth 16 hours before the study, harvested from peritoneal fluid and peripheral blood, and isolated on Ficoll-Hypaque. F-met-leu-phe (FMLP) chemoattractant (10(-7) M) was used to induce migration of neutrophils across 3 mu filters. The filters were removed, mounted on slides, stained, and counts averaged for five oil immersion fields for each of three wells. Data were expressed as number of neutrophils per oil immersion field. Peritoneal neutrophil chemotaxis was significantly decreased in Group 1 (10.3 +/- 8.1) compared with Groups 2 (17.0 +/- 7.3) and 3 (20.2 +/- 6.4). A similar trend was noted in polymorphonuclear leukocytes from peripheral blood (Group 1: 13.1 +/- 7.8, Group 2: 18.2 +/- 6.7, Group 3: 17.4 +/- 5.9; P = 0.1). This impairment in neutrophil chemotaxis may contribute to the high rate of septic complications observed in the jaundiced host. PMID- 1739227 TI - Pericardiotomy improves left ventricular compliance during sepsis-induced pulmonary artery hypertension. AB - Sepsis-induced pulmonary artery hypertension (SIPAH) causes an increase in right ventricular (RV) afterload, dilatation of the RV, leftward shift of the interventricular septum (IVS), and therefore decreases left ventricular compliance (LVC). This study was designed to evaluate the role of pericardiotomy during SIPAH as an alternative to vasodilators (which cause a detrimental increase in shunt fraction) to improve LVC. Systemic and pulmonary hemodynamics, pulmonary function, RV, and LVC were acquired at baseline (BL), during SIPAH with closed pericardium (PAHCP) and after opening the pericardium (PAHOP). Systemic hemodynamics and pulmonary function did not change significantly during the experiment. The infusion of live bacteria induced a significant rise in mean pulmonary artery pressure from 16 +/- 5.3 at BL to 36.8 +/- 3.3 and 35.0 +/- 6.4 mm Hg during PAHCP and PAHOP, respectively, (P less than 0.05). Pulmonary vascular resistance index and right ventricular stroke work index (RVSWI) displayed a similar rise in response to SIPAH (P less than 0.05 vs BL). Pericardiotomy did not affect pulmonary hemodynamics or RVSWI. Right ventricular contractility did not increase following pulmonary hypertension while the pericardium was closed (440 +/- 78 vs 410 +/- 125, P less than 0.05); however, it rose, although not significantly, to 615 +/- 326 after pericardiotomy. RV time tension index displayed a rise during SIPAH with the pericardium intact and returned to baseline values after pericardiotomy; however, these changes were not significant. RVC did not change significantly throughout the experiment. In contrast, LVC decreased significantly after SIPAH and significantly improved after pericardiotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739228 TI - Treatment priorities in patients with traumatic rupture of the thoracic aorta. AB - Autopsy studies reveal that 90 percent of patients with traumatic rupture of the thoracic aorta (TRTA) die at the scene of the accident and 25 percent of those reaching the hospital do not survive their injuries. Treatment priorities in patients with TRTA and associated life-threatening head and intra-abdominal injuries have not been adequately studied. The authors reviewed their experience with 57 consecutive patients sustaining TRTA to establish treatment priorities in these multiply injured patients. The mean age of the population was 35 years (43 men, 14 women). Hospital mortality was 24 percent; the most common cause of death was hemorrhage. Fully 95 percent of the patients had associated injuries requiring operative intervention. Abdominal injuries requiring laparotomy were present in 20 patients (35%): 14 splenic injuries, 8 liver injuries, 3 pancreatic injuries, and 3 mesenteric lacerations. Twenty-eight patients (49%) had orthopaedic injuries requiring operative fixation. Maxillofacial injuries requiring surgical repair occurred in 20 patients (35%). Fifteen patients (26%) sustained significant closed head injuries, but only 1 required craniotomy for hemorrhage. Nine hemodynamically unstable patients with intra-abdominal hemorrhage underwent immediate laparotomy for control of bleeding followed by aortography and aortic repair (2 deaths, 22%). Seven hemodynamically stable patients had aortography followed by laparotomy for control of intra-abdominal hemorrhage with subsequent thoracotomy (1 death, 14%). Thirty stable patients underwent aortography followed by immediate thoracotomy; 22 required no further procedures, while 8 required an additional operation (7 death, 23%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739229 TI - Computed tomography and diagnostic peritoneal lavage. Complementary roles in blunt trauma. AB - Viewpoints regarding the use of computed tomography (CT) and diagnostic peritoneal lavage (DPL) in the evaluation of stable blunt abdominal trauma patients remain polarized and their respective roles are ill-defined. To further clarify their independent and combined value, the authors report the results of a prospective study of their use in adult patients satisfying the entry criteria of major blunt torso trauma, hemodynamic stability, equivocal and unreliable abdominal examination, and absence of both before abdominal surgery and unstable pelvic fractures. The 116 patients admitted to the study over an 11-month period were first submitted to a CT scan using a 9800 series GE scanner (General Electric Medical Systems; Milwaukee, WI). After its review with the faculty CT radiologist, the surgeon recorded his decision as to the need for the laparotomy. All patients were then subjected to DPL and the results recorded as recommending laparotomy based on finding aspiration of greater than 10 cc of blood or greater than or equal to 100,000 RBC/mm3 greater than W 500 WBC/mm3, or positive gram stain. A final decision was then formulated based on information gained from both studies. Actual need for operation or observation was recorded based on ultimate outcome in observed patients or upon findings at laparotomy. Initial laparotomy was performed in 22 patients; yet only 17 had injuries requiring repair. Unnecessary laparotomy was recommended by DPL in 15.5 percent of patients vs 0.8 percent by CT (P greater than .01), while inappropriate observation was recommended by DPL in 1.7% vs 6.9% by CT (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739230 TI - Prostaglandin E2 in duodenal ulcer complications. AB - Prostaglandins are presumed to have cytoprotective properties and may play a role in the pathogenesis of duodenal ulcer and its complications. To evaluate this hypothesis, 35 patients with either duodenal ulcer bleeding (18 patients) or gastric outlet obstruction (17 patients) were investigated. Biopsies were taken from gastroduodenal tissues and secretions for prostaglandin E2 (PGE2) levels. These levels were compared to those taken from the same areas during a later endoscopy. A correlation was found between the severity of the clinical endoscopic findings and PGE2 levels. Increased levels of PGE2 were found in the quiescent phase and decreased levels found during the deteriorated phase. These differences of PGE2 levels were found to be of significant value (P less than 0.002). Furthermore, the patients in which the PGE2 levels were decreased at second endoscopy needed surgery. PGE2 may, thus, be a factor in duodenal ulcer pathogenesis and its complications, and be used as a prognostic marker and guide. PMID- 1739231 TI - Primary aortoenteric fistulas. AB - Aortoenteric fistulas were first reported in 1822. Primary aortoenteric fistulas are uncommon (less than 200 cases reported). Secondary aortoenteric fistulas are a well-recognized complication of prosthetic grafts (incidence from 0.4 to 2.4%). Atherosclerosis, gallstones, foreign bodies, carcinomas, and diverticular disease are the most common etiologies. Diagnosis is difficult with most studies being nondiagnostic. A high incidence of suspicion is required to successfully diagnosis preoperatively. Surgical repair is required for survival of the patients and should consist of the following: 1) primary closure of the intestinal defect, 2) either primary anatomical repair with a prosthetic graft or extra-anatomical vascular reconstruction, depending upon the presence or absence of infection, and 3) treatment with appropriate antibiotics. One of the largest series of primary aortoenteric fistulas from a single institution consisting of three cases secondary to aneurysmal and granulomatous disease is discussed. PMID- 1739232 TI - Phytobezoar obstruction of a Meckel's diverticulum. PMID- 1739233 TI - The carpal tunnel syndrome: Part I. AB - The carpal tunnel syndrome is a compression of the median nerve within the carpal tunnel with very specific signs and symptoms. Anatomical dissection of 156 wrists is presented and then the authors compare their findings with the findings of other investigators. The purpose of this article is not to present results but rather to discuss the anatomic entities involved with the syndrome and to present the open treatment modality. PMID- 1739234 TI - Increased sympathetic nervous activity and the effects of its inhibition with clonidine in alcoholic cirrhosis. AB - OBJECTIVE: To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. DESIGN: Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. PATIENTS: Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. INTERVENTIONS: Intravenous clonidine. MAIN OUTCOME MEASURES: Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. MAIN RESULTS: In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. CONCLUSIONS: The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis. PMID- 1739235 TI - The natural history of electrocardiographic preexcitation in men. The Manitoba Follow-up Study. AB - OBJECTIVE: To examine the natural history of preexcitation occurring on the routine electrocardiogram (ECG). DESIGN: A longitudinal cohort study of 3983 originally healthy men followed prospectively for 40 years. SETTING: Free-living (community-dwelling) study members residing predominantly in Canada. PARTICIPANTS: Nineteen male study members with preexcitation occurring during routine examination in the 40-year follow-up of the Manitoba Follow-up Study. MEASUREMENTS: Routinely requested clinical examinations and ECGs, supplemented by information supplied by the study member or his physician. MAIN RESULTS: Ten study members were found to have preexcitation at enrollment, for a prevalence of 2.5 per 1000 (95% CI, 1.2 to 4.6). A delta wave was first detected during follow up in an additional nine study members. Seventeen of 19 study members did not have the delta wave at some later time, and preexcitation was intermittently present in most of these members. Over time there was a loss of preexcitation, with 15 of 19 study members no longer exhibiting a delta wave by the end of follow-up. Five of 11 study members with symptoms had physician confirmation of an arrhythmia. Fourteen study members remain alive, and none of the five deaths was attributed to preexcitation. CONCLUSIONS: Preexcitation found on routine ECG in our originally healthy male study group did not confer excess morbidity or mortality, even in those study members who developed symptomatic arrhythmias. Most preexcitation was intermittent and disappeared over time. PMID- 1739236 TI - Acetazolamide in the treatment of acute mountain sickness: clinical efficacy and effect on gas exchange. AB - OBJECTIVE: To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness. DESIGN: A randomized, double-blind, placebo controlled trial. SETTING: The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska. PARTICIPANTS: Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness. INTERVENTION: Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study. MAIN OUTCOME MEASURES: An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours. MAIN RESULTS: After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045). CONCLUSION: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange. PMID- 1739237 TI - Treatment of Mycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. The California Collaborative Treatment Group. AB - OBJECTIVE: To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen. DESIGN: A phase II, multicenter clinical trial. SETTING: Four university-affiliated medical centers. PATIENTS: Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen. INTERVENTIONS: Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator. MEASUREMENTS: Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined. MAIN RESULTS: The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common. CONCLUSIONS: A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection. PMID- 1739238 TI - Conjugal Graves disease. PMID- 1739239 TI - Career differences between primary care and traditional trainees in internal medicine and pediatrics. AB - OBJECTIVE: To assess the relation of Primary Care Residency Training to career choice, board certification, and practice location of internists and pediatricians. DESIGN: Cohort study with up to 8 years of follow-up. SETTING: The United States. PARTICIPANTS: The 17,933 residents trained in all internal medicine (13,750) and pediatrics (4,183) residency programs between 1977 and 1982 were studied using information from the National Resident Matching Program, the AMA Physician Masterfile, the Area Resource File, and a telephone survey. MEASUREMENTS: Career choice, board certification, and practice location were studied in relation to five explanatory variables: type of residency (primary care or traditional track), gender, year of medical school graduation, educational orientation of the teaching hospital, and medical school prestige. MAIN RESULTS: Graduates of primary care residency training programs chose careers in generalist primary care significantly more often than did graduates of traditional tracks in both internal medicine (72% compared with 54%) and pediatrics (88% and 81%, respectively; P less than 0.001 for both values). Board certification rates in internal medicine were statistically higher for graduates of primary care training programs (80%) than for graduates of traditional programs (76%, P = 0.002) but were not statistically significant for both groups of pediatric graduates. Graduates of primary care programs in pediatrics and internal medicine practiced in medically less served communities more often than did graduates of traditional programs. CONCLUSION: Graduates of primary care residency training programs in internal medicine and pediatrics differ from graduates of traditional residency programs in career choices, board certification rates, and practice locations. PMID- 1739240 TI - Wegener granulomatosis: an analysis of 158 patients. AB - OBJECTIVE: To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. DESIGN: Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). MEASUREMENTS: Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. MAIN RESULTS: Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). CONCLUSIONS: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens. PMID- 1739241 TI - The health transition in developing countries: a role for internists from the developed world. AB - Demographic and epidemiologic changes that have occurred in the past five decades in many developing countries provide new opportunities for internists from developed countries to contribute to improvements in international health. These changes, called the "health transition," are characterized by major growth in the number and proportion of middle-aged and elderly persons and in the frequency of the chronic diseases that occur in these age groups. The health transition is the result of concentrated national and international efforts to improve maternal and child health by emphasizing primary care and community-organized outreach services. In many developing countries, such efforts have been responsible for a decrease in the birth rate; reduced maternal mortality; improved preventive services; and a vigorous therapeutic approach to infantile diarrhea and respiratory infection, which, in turn, have resulted in the reduced infant mortality and the increased life expectancy that defines the health transition. These changes, often accompanied by increasing urbanization and industrialization, are creating health problems similar to those seen in the "developed" world but are occurring in countries that have far fewer resources. Internists interested in working in developing countries can therefore bring their skills, experience, and perspective to bear on these problems, primarily by working within well-structured programs, the aim of which is to strengthen the capacity of the organizations and institutions within these countries to cope with the rising tide of chronic adult diseases. PMID- 1739242 TI - Increasing utilization of allogeneic bone marrow transplantation. Results of the 1988-1990 survey. AB - OBJECTIVE: To determine the pattern and frequency of allogeneic bone marrow transplantation from related and unrelated donors from 1988 to 1990. DESIGN AND SETTING: Survey of 342 institutions in 47 countries. MEASUREMENTS: Numbers of patients receiving bone marrow transplantation for specific disease categories at institutions with active allogeneic bone marrow transplant programs. MAIN RESULTS: Patients (14,745) received allogeneic bone marrow transplantation between 1988 and 1990; of these, 1153 (8%) were from unrelated donors. Reasons for transplantation were acute leukemia (47%), chronic myelogenous leukemia (27%), lymphoma and other malignancies (10%), severe aplastic anemia (9%), and other nonmalignant diseases (7%). The number of allogeneic bone marrow transplants per million persons differed among countries, averaging 7.7 per million in North America and 5.7 per million in western Europe. CONCLUSIONS: The use of allogeneic bone marrow transplantation continued to increase at a rate of more than 600 additional patients and 25 new transplant teams annually. This rise is due in part to increasing use of unrelated volunteers as donors. Resources allocated for transplants vary widely among countries. PMID- 1739243 TI - Training primary care physicians. PMID- 1739244 TI - Clonidine for portal hypertension: a sympathetic solution? PMID- 1739245 TI - Anemia of chronic disease: a misnomer? PMID- 1739246 TI - Anemia of chronic disease: a misnomer? PMID- 1739247 TI - Anemia of chronic disease: a misnomer? PMID- 1739248 TI - Regional variations in plasma fibrinogen. PMID- 1739249 TI - Hyperprolactinemia, galactorrhea, and atenolol. PMID- 1739250 TI - Cefotetan-induced singultus. PMID- 1739251 TI - Augmented Valsalva maneuver for supraventricular tachycardia in the young. PMID- 1739252 TI - Does low total creatine kinase rule out myocardial infarction? PMID- 1739253 TI - Does cerebral toxoplasmosis therapy protect against pneumocystitis in AIDS? PMID- 1739254 TI - Does radiation increase survival in nonresectable lung cancer? PMID- 1739255 TI - Laser surgery for the treatment of larynx carcinomas: indications, techniques, and preliminary results. AB - The authors have developed four different types of endolaryngeal laser resections for the treatment of larynx carcinomas. These new techniques are based on traditional concepts employed in partial larynx resections. From 1986 onward, 110 patients with laryngeal cancers were treated by endoscopic laser surgery. One hundred six patients were operated on for cure and 4 for palliation. In 9 cases of T3 tumor, complete removal of the tumor was not possible, requiring total laryngectomy. In all T2 cancers of the glottis and subglottis (n = 36), a total resection was possible. Additional staged neck dissection was performed in 16 cases, and postoperative radiotherapy in 10 cases. Follow-up investigations of the patients treated for cure (n = 106) cover a period of 3 to 42 months (mean, 22 months). These revealed 6 recurrences in the larynx, which were treated by laryngectomy. Recurrences in the cervical nodes were seen in 2 patients following resection of a supraglottic tumor and a subglottic tumor, respectively. Seven patients could not be followed up, 4 patients died of intercurrent disease, and 87 patients are alive and free of tumor. At present the number of recurrences and the rate of survival show no significant difference from those previously reported after conventional surgery. The phonatory function is not always predictable and still remains to be investigated. The authors believe that laser surgery may obviate the need for total laryngectomies in selected cases of laryngeal cancer, especially in T2 tumors. However, T3 tumors should not be treated by endolaryngeal laser surgery. PMID- 1739256 TI - Characteristics of late responses to superior laryngeal nerve stimulation in humans. AB - To characterize human thyroarytenoid and cricothyroid muscle responses to stimulation of the internal (sensory) and external (motor) branches of the superior laryngeal nerve (SLN), three awake subjects were studied at rest and during muscle activation with stimulation at different current levels. When only the external branch was stimulated, direct cricothyroid muscle responses were obtained without responses in either thyroarytenoid muscle. When only the internal branch was stimulated, no cricothyroid responses were obtained, but two late thyroarytenoid responses occurred (R1 and R2). The R1 response was usually ipsilateral and had a mean onset latency of 18 milliseconds, while the R2 response was bilateral and occurred between 66 and 70 milliseconds. Both responses tended to decrease in latency and increase in amplitude with increased stimulation level. The similarity of R1 to the adductor response and R2 to other late responses is discussed. PMID- 1739257 TI - Pediatric transbronchial lung biopsy. AB - A retrospective review of 25 transbronchial lung biopsies in 19 pediatric patients is reported. Nineteen of these procedures used a rigid ventilating bronchoscope and a small cup biopsy forceps. The indications included diffuse pulmonary infiltrates in the immunocompromised patient, severe hyaline membrane disease, tumor, and lung transplant. In 84% of the procedures, adequate tissue was obtained. There was a 12.5% incidence of pneumothorax and no significant pulmonary hemorrhage. PMID- 1739258 TI - Dysphagia following various degrees of surgical resection for oral cancer. AB - Postoperative swallowing problems were investigated in 20 patients who had undergone various degrees of surgical resection for oral cancer. The swallowing problems were evaluated on the basis of type of food, degree of aspiration, and duration of postoperative nasogastric tube feeding. Two patients with tongue cancer who had had hemiglossectomy without reconstruction ate normal food without aspiration within a week after operation. Eight patients who had undergone two- to three-quarter glossectomy for tongue cancer ate gruel with no or occasional liquid aspiration. Among 4 patients who had had near-total or total glossectomy for tongue cancer, 3 ate thin gruel or liquid with occasional aspiration. The other could not eat orally because of consistent severe aspiration. One patient with mouth floor cancer underwent resection of the mouth floor in combination with hemiglossectomy and she ate gruel without aspiration. Among 5 patients with mouth floor cancer who had had surgical removal accompanied by near-total or total glossectomy, 3 ate gruel with no or occasional liquid aspiration, 1 ate thin gruel with no aspiration, and the other could not eat orally. A diagnosis of T4 lesions, extensive removal of the tongue base, removal of the geniohyoid and mylohyoid muscles, and removal of the lateral pharyngeal wall were significantly related to poor swallowing function. PMID- 1739259 TI - Voice analysis of patients with endoscopically treated early laryngeal carcinoma. AB - Endoscopic laser resection of early (T1) laryngeal carcinoma has been advocated as an alternative to radiotherapy. Heretofore, the voice characteristics following this procedure have been addressed in only one review, which included patients treated by irradiation and laser resection. We present the first review of voice findings in 22 patients treated only by endoscopic laser resection of their vocal cord carcinomas. Laser resection of selected vocal cord carcinomas produced voice function results acceptable to the patients and was rated by them to be normal to almost normal. Speech pathologists rated the voices to be near normal to mildly abnormal. Voices after laser resection of vocal carcinoma exhibited a slightly higher fundamental frequency, a decrease in intensity and phonatory duration, and markedly higher laryngeal airway resistance. The percentage of voicing showed little deviation from normal, as did mean percentage of perturbations. PMID- 1739260 TI - Open tube versus flexible esophagoscopy in adult head and neck endoscopy. AB - Open tube esophagoscopy is the mainstay of otolaryngic esophageal examination. Over the last 30 years flexible endoscopes have become popular and are challenging the open tube esophagoscope for use in otolaryngic practice. This study examines all open tube esophagoscopies performed on adult patients at the University of Pennsylvania over an 8-year period for the diagnosis and treatment of foreign bodies, strictures, functional disorders, and carcinoma. Open tube esophagoscopy is most useful for foreign body extraction, examination of the cervical esophagus, and dilation of pliable strictures. For most other indications flexible esophagoscopy provides improved visualization with lower morbidity. For patients with squamous cell carcinoma of the head and neck we found a 1.4% incidence of secondary esophageal malignancies and a 28% incidence of false-negative barium swallow studies. We recommend esophagoscopy for all patients with carcinoma of the upper aerodigestive tract. The otolaryngologist should be adept at both flexible and open tube esophagoscopy in order to allow optimal examination of and therapeutic intervention in the upper aerodigestive tract. PMID- 1739261 TI - Histopathologic correlates of acute laryngeal allograft rejection in a rat model. AB - This study used both clinical and histopathologic criteria to define the sequence and time parameters of rejection in histoincompatible vascularized rat laryngeal allografts. Clinical onset of rejection was characterized at 1 week by graft edema. Pathologic examination at this time revealed arterial wall thickening and a diffuse lymphocytic and macrophage mucosal infiltrate. At 14 days, the graft was encased in an inflammatory exudate with no visible cartilaginous structure. This correlated microscopically with a lymphocytic infiltrate of the lamina propria, loss of minor salivary glands, and squamous metaplasia of the surface respiratory epithelium. Arterial thrombosis was always correlated with tissue necrosis, but venous occlusion, occurring more than 2 days after transplantation, was not an independent determinant of graft viability. Definition of the time sequence and histopathology of rejection will allow future determination of the efficacy of various immunosuppressive regimens. PMID- 1739262 TI - Herpes zoster oticus: treatment with acyclovir. AB - Herpes zoster oticus produces facial paralysis with a low recovery rate. Acyclovir, a specific virostatic drug, was given intravenously in five herpes zoster oticus patients, and in three of them was followed by oral therapy. In follow-ups of 1 to 24 months, one patient had grade I recovery, three patients grade II, and one grade III. These good results encourage the use of acyclovir in herpes zoster oticus patients. PMID- 1739263 TI - Elastin at the hinge portion of the eustachian tube cartilage in specimens from normal subjects and those with cleft palate. AB - The density of elastin in the intermediate portion between the lateral lamina and the medial lamina of human eustachian tube (ET) cartilage was examined in six normal adults, seven normal children, and six children with cleft palate (CP) in order to obtain information about how the physical properties of the ET cartilage differ as a function of age and presence of CP. Cross sections of the midcartilaginous portions of the ETs that had been stained with Weigert's elastin stain were photographed at uniform magnification, the area for study was projected, and the meshlike are of the ET cartilage that stained elastin-positive was represented on paper by lines. A digitizer was used to measure the total length of all the lines representing elastin in each photomicrograph, and the mean was determined for each of the three groups. The mean density of elastin was significantly greater in normal adults than in normal children (Student's t test, t = 2.781; p less than .02). It was also significantly greater in normal children than in CP children (Wilcoxon t = 24.0; p less than .05). These results appear to indicate that CP children have poorer elasticity in this area of the ET cartilage, which might cause functional obstruction (floppiness) of the ET in those children. PMID- 1739264 TI - Cochlear blood flow and microvascular resistance changes in response to hypertonic glycerol, urea, and mannitol infusions. AB - The effect of hyperosmotic agents on cochlear blood flow (CBF) was tested in normal guinea pigs and in guinea pigs having prior unilateral operations to ablate the endolymphatic duct. Laser-Doppler-measured CBF was normalized to remove apparent changes related directly to systemic blood pressure. Hyperosmotic fluids were given via venous infusion: glycerol (20% and 40% solutions), urea (10%, 30%, and 40% solutions), and mannitol (40% solution). All agents were dissolved in 0.9% saline and the mixtures were given at a rate of 0.3 to 0.6 mL/min for 5 minutes. Control infusions were of 0.9% saline and isotonic dextran 70 (Pharmacia). All hyperosmotic infusions resulted in similar increases in normalized cochlear blood flow (nCBF) that extended to a maximum of 300% of the baseline value in a dose-dependent way during the infusion time period. Within approximately 30 minutes following infusions, nCBF had returned to baseline levels. Saline infusion alone had little effect on nCBF, but isotonic dextran 70 gave a sustained increase to 122% of the baseline levels. There was no difference between the responses of nCBF in hydropic and normal cochleas for either control or hyperosmotic solutions. Measurements of systemic hematocrit at time intervals during and following the infusions showed that transient reductions of up to approximately 8% (for the maximum osmotic challenge) occurred during the infusion. It is concluded that the hyperosmotic treatments tested here are equally effective for short-term enhancements of nCBF in both normal and hydropic cochleas. The basis of the flow increase is partially rheologic and partially due to a local vasodilation. PMID- 1739265 TI - Chronic perilymph fistula in the guinea pig with implications in the human. AB - To improve understanding of the pathophysiology of perilymph fistulas, a predictable animal model of a chronic fistula was developed. Our findings suggest that guinea pig fistulas do not remain patent for prolonged periods. By extrapolating these findings to humans, we postulate that the symptoms and signs of perilymph fistula are possibly due not to one prolonged constant fistula, but rather a series of "blowouts" from an inherent congenital or posttraumatic weak spot in either the round or oval window. We feel that a diagnosis of perilymph fistula must be considered in any patient presenting with a Meniere's-like symptom set concomitant with a congenital inner ear deformity or a history of inner ear trauma. PMID- 1739266 TI - Chondrosarcoma of the larynx. PMID- 1739267 TI - Fine-needle aspiration of salivary glands: its utility and tissue effects. AB - Any diagnostic procedure requires a circumspect decision on its clinical utility. Otherwise, it risks being only an additional evaluation that is not cost effective. In the case of fine-needle aspiration biopsy of lesions of salivary glands, there are unquestioned clinical indications; none, however, merit its inclusion as part of a systematic evaluation. Attention is also called to the possible negation of a histopathologic diagnosis because of the tissue effects of the fine-needle aspiration. PMID- 1739268 TI - The three bellies of the canine cricothyroid muscle. AB - The cricothyroid muscle is capable of multiple functions, including vocal cord elongation and adduction. In addition, the cricothyroid can lengthen the glottis as well as provide posture to the cricothyroid joint. The purpose of the present study is to demonstrate that the many functional capabilities of the cricothyroid are a reflection of the existence of separate bellies within the muscle. Microdissection revealed three distinct muscle bellies within the cricothyroid: rectus, oblique, and horizontal. These differ in fiber orientation (rectus 79 degrees, oblique 48 degrees, horizontal 7 degrees) and are separated by fascial planes. Histochemistry showed that these three bellies are composed of different percentages of slow twitch fibers (rectus 31.3%, oblique 43.3%, horizontal 39.6%). Finally, electromyography demonstrated differences in the electrical activity patterns of the three bellies. It is concluded that the cricothyroid muscle is composed of three distinct muscle bellies that probably play separate roles in the complex function of this muscle. PMID- 1739269 TI - Hemoglobin and 2,3-diphosphoglycerate levels in transfused dialysis patients with myocardial infarction. AB - Thirty frequently transfused patients on long term hemodialysis were studied and a similar number of age and sex-matched patients who were infrequently transfused were used as a control group to ascertain the influence of a previous myocardial infarction (MI) on transfusion requirements. The frequency of previous MI on electrocardiogram (ECG) in the transfused and control groups was similar (40 percent and 37 percent, respectively). In frequently transfused dialysis patients with MI, the hemoglobin level (transfusion trigger) at which these patients were transfused was higher than that of frequently transfused patients without MI (8.3 +/- 1.5 g per dl vs. 6.9 +/- 1 g per dl, p less than 0.01) which indicated that patients without MI tolerated a greater degree of anemia than those with MI. The 2,3-diphosphoglycerate (2,3-DPG) levels were significantly elevated in all transfused patients when compared to matched controls. However, levels of 2,3-DPG were significantly higher in MI patients receiving frequent transfusions than in other transfused patients, suggesting oxygen demands may not have been fully met despite the frequent transfusions. The results suggest levels of 2,3-DPG deserve further study in relation to the adequacy of tissue oxygenation in anemic dialysis patients. PMID- 1739270 TI - Conversion of a qualitative screening test to a quantitative measurement of urinary cystine and homocystine. AB - Qualitative urinary screening procedures were converted to quantitative methods for urinary cystine and homocystine based on the reactions between these amino acids and cyanide-nitroprusside reagents. Cystine and homocystine are quantified by the measurement of absorbances at 521 and 524 nm, respectively. Cyanide nitroprusside reacts with both cystine and homocystine. However, in the presence of silver nitrate, only homocystine reacts to produce a magenta color. Following the cyanide-nitroprusside reaction, absorbance must be read within three minutes for cystine and immediately for homocystine. The stability of the absorption spectra has no apparent effect on these quantitative assays. Amino acid concentrations are expressed as ratios to creatinine, which tends to eliminate false negative results in dilute urine specimens. The normal urine value for cystine and homocystine combined is 66.8 +/- 52 (n = 50) mg per g creatinine. The normal value for homocystine alone is 29.9 +/- 16.8 (n = 24) mg per g creatinine. The simplicity of these procedures allows these quantitative methods to be used as screening tests for cystinuria and homocystinuria. PMID- 1739271 TI - Evaluation of the SonoClot Analyzer for the measurement of platelet function in whole blood. AB - A viscoelastometer, the SonoClot Coagulation Analyzer, has been proposed for use in the evaluation of platelet function. The purpose of this study was to evaluate systematically this instrument when used with whole blood. Under laboratory conditions, the coefficient of variation (cv) of determinations of whole blood activated clotting time (ACT) on the instrument was approximately 7.0 percent. In contrast, the cv of measurements on whole blood related to the graphic events associated with clot formation ranged from 9.2 to 41.7 percent. Because of the large and variable cvs associated with these measurements of clotting, the SonoClot Analyzer cannot presently be recommended for use in studies designed to examine quantitatively the clotting function in whole blood. PMID- 1739272 TI - Hypertension and vascular dementia. AB - Postmortem surveys on patients treated for chronic hypertension often fail to demonstrate significant vessel changes. Nevertheless, hypertensive alterations in the brain can include infarcts and hemorrhages. Autopsies in a primary care hospital have shown that hypertension can affect arteries, arterioles, and capillaries in various patterns and degrees in the brain. These vascular lesions may be associated with large and small infarcts and hemorrhages in isolated or diffuse patterns. Widespread cerebral edema can occur with rapidly progressive hypertension. Atherosclerosis, arterial and arteriolar fibrinoid necrosis, and micro-aneurysms may be observed. Chronic hypertensive encephalopathy causes vascular dementia and can be associated with subcortical arterial and arteriolar leukoencephalopathy, leukoaraiosis and/or Binswanger's disease. Epidemiologic evaluations based on complete autopsy studies need to be correlated with compliance of therapy, appropriate diagnosis of hypertension, and its long-term effects on the nervous system. Although persistent poorly controlled hypertension is known to damage the brain both acutely and chronically, the effects of intermittent hypertension remain to be defined. PMID- 1739273 TI - Ionized calcium buffering in the transfused anhepatic patient: Ab initio calculations of calcium ion concentrations. AB - Homeostatic control of ionized calcium can be volatile during liver transplantation, particularly during the anhepatic stage. Recently, an opportunity arose to evaluate an 11-year-old girl who developed persistent ionic hypocalcemia during a prolonged anhepatic period subsequent to the failure and removal of the graft. The patient was remarkable for having survived a 34-hour anhepatic interval before a second and successful orthotopic liver transplant. Ionic hypocalcemia (ionized calcium less than 1 mmol per L) coexisted with significant hypercalcemia (total calcium greater than 5 mmol per L) during this anhepatic interval. The discrepancy was due to high concentrations of citrate, which accumulated from the multiple transfusions of citrated blood, and the inability to metabolize citrate in the anhepatic state. Using a mathematical model to solve for free calcium ion concentration in the presence of multiple ligands, it is demonstrated that prolonged hypercitricemia markedly alters the calcium ion buffering properties of blood, and these changes must be recognized in order to prevent adverse clinical consequences of ionic hypocalcemia. PMID- 1739274 TI - The informative abstract. PMID- 1739275 TI - Alopecia by a different name. A matter of splitting hairs. PMID- 1739276 TI - Search for Streptococcus. PMID- 1739277 TI - Tender periungual nodules. Myrmecia (deep palmoplantar warts). PMID- 1739278 TI - Persistent painful plantar masses. Epithelioma cuniculatum. PMID- 1739279 TI - Pruritic pigmented papules posing permanent problems. Urticaria pigmentosa (UP) with secondary anetoderma. PMID- 1739280 TI - Acyclovir in the prevention of severe aphthous ulcers. PMID- 1739281 TI - Pseudocysts around the interphalangeal joints as a manifestation of calcinosis cutis in a patient with lupus nephritis undergoing hemodialysis. PMID- 1739282 TI - Complement-fixing activity to melanin-producing cells preceding the onset of vitiligo in a patient with type 1 polyglandular failure. PMID- 1739283 TI - Pharmacologic doses of lovastatin do not predictably affect the course of psoriasis. PMID- 1739284 TI - Radiation therapy as an alternate therapy for locally recurrent acral lentiginous malignant melanoma. PMID- 1739285 TI - The role of streptococcal infection in the initiation of guttate psoriasis. AB - BACKGROUND AND DESIGN: Although the association between streptococcal infection and guttate psoriasis is well known, to date there has been little information on whether only limited groups and/or serotypes of beta-hemolytic streptococci are involved. One hundred eleven patients with a sudden onset or deterioration of psoriasis were investigated for evidence of streptococcal infection. Of these patients, 34 had acute guttate psoriasis, 30 had a guttate flare of chronic psoriasis, 37 had chronic plaque psoriasis, and 10 had other types of psoriasis. RESULTS: Serologic evidence of recent streptococcal infection was present in 19 (58%) of 33 patients with acute guttate psoriasis compared with seven (26%) of 27 patients with guttate exacerbations of chronic psoriasis. Streptococcus pyogenes was isolated from 19 (17%) of all 111 patients (9 [26%] of 34 with acute guttate psoriasis, four [13%] of 30 with guttate exacerbations of chronic psoriasis, and five [14%] of 37 patients with chronic psoriasis) compared with seven (7%) of 101 of a control population of patients being seen for treatment of viral warts. Other beta-hemolytic streptococci were found with equal frequency in the study and control populations. Thirteen isolates of 10 different streptococcal serotypes were obtained from the 64 patients with guttate psoriasis. These serotypes were similar in distribution and prevalence to those present in the local community. CONCLUSIONS: This study confirms the strong association between prior infection with S pyogenes and guttate psoriasis but suggests that the ability to trigger guttate psoriasis is not serotype specific. PMID- 1739286 TI - Burn depth estimation using indocyanine green fluorescence. AB - Expedient primary excision of deep dermal and full-thickness burn wounds with subsequent skin grafting is the standard of care in most burn institutions, but differentiating full-thickness from partial-thickness burns is often difficult. Because accurate early assessment of burn depth may improve care, a variety of technical methods have attempted to measure burn depth but these methods have had limited success. We describe a new technique to determine burn depth that uses infrared (840- to 850-nm) fluorescence emission from intravenously administered indocyanine green following excitation with infrared (780 nm) and UV light (369 nm). Full-thickness and partial-thickness burns in hairless rat skin were distinguished based on the infrared-induced and UV-induced fluorescence intensity ratios relative to normal, unburned skin immediately after the burn and on post burn days 1 through 3 and 7. Dual-wavelength excitation of indocyanine green infrared fluorescence can delineate full-thickness from partial-thickness burns at an early date, allowing prognosis, surgical planning, and early primary excision and grafting. PMID- 1739287 TI - Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases. AB - BACKGROUND: Toxic epidermal necrolysis is a potentially severe mucocutaneous affliction whose cause is usually drug related. To further characterize the nature of the dermal mononuclear infiltrate as well as the epidermal alterations observed by standard microscopy, we studied five cases of toxic epidermal necrolysis using labeled monoclonal antibodies. RESULTS: On clinically involved areas of skin, the following occurs: (1) the dermal infiltrate is composed mainly of activated T lymphocytes, with a predominant helper phenotype; (2) the number of Langerhans cells is decreased; and (3) keratinocytes express HLA-DR molecules, normally absent on their surface. CONCLUSIONS: These findings, although not specific, are consistent with an immune cellular reaction, but they could also be linked to an inflammatory reaction initiated by epidermal damages whatever its primary mechanism. PMID- 1739288 TI - Identification of cicatricial pemphigoid antigens. AB - The nature of skin antigens defined by antibodies in patients with cicatricial pemphigoid was studied with use of the 1 mol/L of sodium chloride split skin technique and Western immunoblot analysis. Antibodies in the serum samples of three of seven patients with cicatricial pemphigoid reacted to the epidermal side of 1 mol/L of sodium chloride split skin, and antibodies in the serum sample of one patient reacted to the dermal side. With Western immunoblot analysis, three patients had antibodies to antigens in the epidermal extracts of skin. The antibodies reacted in all patients to a 160-kd antigen and in one patient to an additional 230-kd antigen. These two antigens are similar in molecular weight to the 230-kd major bullous pemphigoid antigen and to the 160-kd minor bullous pemphigoid antigen. However, while the basement membrane zone antibodies present in cicatricial pemphigoid were most often directed to the 160-kd antigen, those present in 38 patients with bullous pemphigoid reacted most often (in 34 patients [89%]) to the 230-kd antigen. None of the serum samples reacted to antigens in dermal extracts that contained the epidermolysis bullosa acquisita antigen. These results indicate that the basement zone membrane antibodies present in cicatricial pemphigoid are directed in part to epidermal antigens that are similar in molecular weight to bullous pemphigoid antigens. However, the frequency of reactions to different basement membrane zone antigens differs in the two diseases, which may account for the clinical differences between the two conditions. PMID- 1739289 TI - Role of excision repair in UVB-induced depletion and recovery of human epidermal Langerhans cells. AB - Skin exposure to UVB radiation deprives the antigen-presenting function and OKT6 monoclonal antibody-binding characteristics of Langerhans cells. Decrease of Langerhans cell population could be relevant to immune surveillance disturbance in the UV-exposed skin. Patients with xeroderma pigmentosum exhibit a thousandfold higher risk for sunlight-induced skin cancers than patients with normal skin, and also have various defects in cellular immunity. Therefore, studies of numerical and structural changes in epidermal Langerhans cells of patients with xeroderma pigmentosum after UVB irradiation compared with normal subjects may contribute to understanding the role of antigen-presenting cells in photocarcinogenesis. The effect of UVB radiation on OKT6+ Langerhans cells was studied in epidermal sheets obtained from irradiated normal subjects (36 and 49 years old) and subjects with xeroderma pigmentosum complementation group A (21 years old), complementation group D (32 years old), and variant (35 and 60 years old). Langerhans cell densities in chronically sunlight-exposed skin were remarkably reduced in patients with xeroderma pigmentosum group A but only slightly in those with xeroderma pigmentosum variant and in normal subjects compared with covered skin. Structural changes were substantial in Langerhans cells of chronically exposed patients with xeroderma pigmentosum group A but fewer in subjects with other xeroderma pigmentosum groups and in normal subjects. A single irradiation of three times the minimal erythema dose induced a large reduction of Langerhans cells from 3 to 7 days in all subjects. However, subsequent reappearance and return to preirradiated levels was delayed more in patients with xeroderma pigmentosum group A than in those with xeroderma pigmentosum variant and normal subjects. These results indicate (1) an essential role for excisional repair in the UVB-induced depletion, recovery, and maintenance of the epidermal Langerhans cell population, and (2) a possible, but not confirmed, relationship between depletion of Langerhans cells and earlier photocarcinogenesis in xeroderma pigmentosum. PMID- 1739290 TI - The follicular degeneration syndrome in black patients. 'Hot comb alopecia' revisited and revised. AB - BACKGROUND: The history, physical examination, and histologic findings in 10 black women with a common, distinctive form of scarring alopecia (formerly called hot comb alopecia) were retrospectively studied. A detailed history of hair care habits was obtained, and scalp biopsy specimens were examined after both vertical and transverse sectioning. OBSERVATIONS: Poor correlation is noted between the usage of a hot comb and the onset or progression of disease. The earliest observable histologic abnormality is the premature desquamation of the inner root sheath. In severely affected follicles this is followed by a chain of histologic events leading to complete follicular degeneration. CONCLUSIONS: The term follicular degeneration syndrome (FDS) is proposed for this clinically and histologically distinct form of scarring alopecia. Historical information is incompatible with the hypothesis that hot comb usage causes the alopecia. It remains unclear whether the use of any of a variety of hair care products and techniques plays a role in the pathogenesis of this condition. Premature desquamation of the inner root sheath serves as a histologic marker for FDS follicular degeneration syndrome, and may be an important pathogenetic factor. PMID- 1739291 TI - Cutaneous leishmaniasis acquired during military service in the Middle East. AB - BACKGROUND: Cutaneous leishmaniasis is endemic in much of the Middle East. Personnel from more than 55 nations are currently participating in Middle East peacekeeping and military activities. OBSERVATIONS: Twenty-three Fijian members of a military observational force in Sinai, Egypt, acquired cutaneous leishmaniasis. They were treated successfully with 1-month courses of ketoconazole. CONCLUSIONS: Soldiers who acquire cutaneous leishmaniasis may return home to nations where cutaneous leishmaniasis is unknown or rarely diagnosed. Cutaneous leishmaniasis, caused by Leishmania major, may be treated with ketoconazole rather than antimonials. PMID- 1739292 TI - Middermal elastolysis in an elderly man with evidence of elastic fiber phagocytosis. AB - BACKGROUND: Middermal elastolysis is a clinically and histologically distinct entity. This idiopathic loss of dermal elastic fibers has mostly been reported in younger adults. To our knowledge, the present case, which has been followed up for 4 years, is the first to occur in an elderly man. OBSERVATIONS: Two years after the onset of progressive wrinkling of the upper aspect of the thorax, the patient underwent a biopsy. Histologic examination of the specimens confirmed previous findings of middermal elastolysis. Examination of extracutaneous elastic tissue showed normal findings. Electron microscopy demonstrated elastic fibers embraced by macrophages, which is suggestive of elastic fiber phagocytosis. For the following 4 years, the patient has remained in stable clinical condition. CONCLUSIONS: Middermal elastolysis is probably more common than has been assumed so far. It does not affect nondermal elastic tissue. After progressive loss of dermal elasticity in a circumscribed area, a benign course follows, with a stable condition over several years. Electron microscopic findings indicate that elastic fiber phagocytosis is operative in the disappearance of the middermal elastic tissue. PMID- 1739293 TI - Disseminated histoplasmosis in patients receiving low-dose methotrexate therapy for psoriasis. AB - BACKGROUND: Low-dose methotrexate sodium therapy used for nonmalignant disease has been associated with a variety of opportunistic infections with pathogens occurring in patients with defective cellular immunity. This article describes the unusual development of disseminated histoplasmosis as a probable complication of immunosuppression resulting from use of methotrexate. OBSERVATIONS: We report the cases of three patients in whom disseminated histoplasmosis developed while receiving low-dose methotrexate therapy for psoriasis. Disease manifestations were unusually severe in two of the three patients. All three cases were disseminated, and two cases resulted in illnesses requiring intensive medical treatment. Each patient responded appropriately to antifungal treatment, although one patient has required long-term suppressive treatment because of persistent Histoplasma antigenuria. These cases illustrate the risk for opportunistic fungal infections in patients receiving low-dose methotrexate therapy for nonmalignant diseases. CONCLUSIONS: Histoplasma should be added to the list of pathogens to be suspected in patients receiving such therapy. PMID- 1739294 TI - Necrobiotic xanthogranuloma. AB - We reviewed 32 cases of necrobiotic xanthogranuloma and 16 cases from the world literature. Necrobiotic xanthogranuloma is a destructive dermal and subcutaneous xanthogranuloma that most frequently involves the face (periorbital region) and trunk. Monoclonal gammopathy is common (IgG-kappa in 23 cases and IgG-lambda in nine cases), and cryoglobulins have also been found. Low complement levels, anemia, and leukopenia are frequently present. Bone marrow examination shows plasma cell proliferation and, rarely, true myeloma. We describe mucosal, muscle, and systemic lesions, including xanthogranulomatous myocardial lesions. The clinical course is chronic and often progressive. Low-dose chlorambucil treatment is safe and effective, but individual patients have responded to treatment with corticosteroids, melphalan, local radiation, and plasma exchange. PMID- 1739295 TI - Basement membrane and fibroblast aberration in blisters at the donor, graft, and spontaneously healed sites in patients with burns. AB - BACKGROUND AND DESIGN: Blisters that developed on spontaneously healed wounds and grafts in 13 patients with burns were analyzed by light, fluorescence, and electron microscopy. RESULTS: Blisters developed on the dermal side of the dermoepidermal junction and occurred more frequently in donor site and healed mesh graft than in split-thickness sheet graft. The four major components of the basement membrane zone (bullous pemphigoid antigen, laminin, type IV collagen, and epidermolysis bullosa acquisita antigen) were reduced in quantity and irregularly deposited at blister sites. Immediately adjacent to the blisters, epidermolysis bullosa acquisita antigen appeared normal in quantity, while laminin, type IV collagen, and bullous pemphigoid antigen levels appeared slightly reduced. Mononuclear infiltrates and autoantibodies were not detected by light microscopy or direct-indirect immunofluorescence, respectively. Ultrastructurally, adjacent dermal fibroblasts demonstrated swollen rough endoplasmic reticulum and vacuolization. CONCLUSIONS: We speculate that blister development in patients with burns is related to defective reorganization of the basement membrane zone in association with dermal fibroblast aberration during wound healing. PMID- 1739296 TI - Natural history of sensitizations in atopic dermatitis. A 3-year follow-up in 250 children: food allergy and high risk of respiratory symptoms. AB - BACKGROUND AND DESIGN: The aim of the study was to define the natural history of sensitization in atopic dermatitis (AD) through cross-sectional (comparison of three age classes) and longitudinal study: 250 children with minor (32.5%), moderate (32.5%), and severe (35%) AD were examined for aeroallergen and food hypersensitivity (skin tests, clinical scoring after allergen elimination, and food challenges). RESULTS: The allergic screening was negative in minor AD and positive in 33% of cases of moderate AD that were concerned with aeroallergen sensitizations with only limited respiratory involvement. This suggests that nonspecific cutaneous hyperreactivity remains an almost exclusive precipitating factor in moderate or minor AD. Severe AD was characterized by a positive allergologic assessment in 100% of patients: food allergens were incriminated as flare factors in 96% of patients, with associated aeroallergen sensitization in 36%. Even at a young age (less than or equal to 2 years), the severe AD group is marked by an extreme frequency of food sensitization (93%) that persists in 73% of children younger than 7 years and 67% younger than 16 years. From the comparison of three age classes, the sequence of food and respiratory sensitization seems to be part of the natural course of AD. Prospective study in 29 children of group 1 (less than 2 years) with a 3-year follow-up confirms the data of the cross-sectional study since 27 had development of aeroallergen sensitization, with respiratory symptoms as early as age 3 years in 23 of these children. CONCLUSION: The detection of food allergy in a child presenting with AD is likely to indicate a prognosis of severe AD and should be considered by dermatologists as a potentially important predictor of further respiratory symptoms. PMID- 1739297 TI - Cutaneous histopathologic, immunohistochemical, and clinical manifestations in patients with hemophagocytic syndrome. Military Medical Consortium for Applied Retroviral Research (MMCARR). AB - BACKGROUND AND DESIGN: The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, beta F-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. RESULTS: The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for beta F-1 and UCHL-1, and a small percentage positive for L-26. CONCLUSION: In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes. PMID- 1739298 TI - Peripheral blood mononuclear cell subsets in patients with severe inherited forms of epidermolysis bullosa. AB - BACKGROUND AND DESIGN: Epidermolysis bullosa (EB) is a group of inherited disorders in which slight trauma to the skin results in blister formation. Patients with severe types of EB suffer cutaneous infections that sometimes progress to septicemia and cutaneous and gastrointestinal carcinomas that are locally aggressive and frequently metastasize. Previous studies have shown deficits in natural killer (NK) cell activity as well as in lymphokine and monokine production in patients with severe forms of EB. Alterations in peripheral blood mononuclear cells, however, which may reflect on immune functions in patients with EB, have received little attention. A prospective study was designed to ascertain if differences existed between subsets of peripheral blood mononuclear cells in patients with severe forms of EB vs healthy control subjects. Thirty patients with clinical and histologic diagnoses of EB and 30 healthy volunteers were studied. Flow cytometric analysis of labeled cells was performed. RESULTS: Absolute numbers of CD3+, CD2+, CD4+, CD19+, NK+, CD29+, and CD45R+ cells were lower in patients with severe types of EB in comparison with controls. The T cells showed decreased numbers of interleukin 2 receptors. An increase in numbers of CD20+, CD4+ CD8+, and CD4-CD8- cells was also observed in patients with severe types of EB. CONCLUSION: Alterations in monocyte and lymphocyte subsets known to affect host immune response were observed in patients with severe forms of EB. Quantitative changes relative to controls included decreased total numbers of T cells with greater decreases in helper cells, decreased NK cells, and a diminished number of interleukin 2 receptors. Such changes have been associated previously with a lower resistance to infections and to neoplasia. The changes in subsets correlated with the severity of the cutaneous and extracutaneous disease in the patients with EB. PMID- 1739299 TI - The protective effect of vitamin E on the hemolysis associated with dapsone treatment in patients with dermatitis herpetiformis. AB - OBJECTIVE: This study looked at whether oral vitamin C and vitamin E would protect the erythrocyte from oxidant damage caused by dapsone in patients with dermatitis herpetiformis. DESIGN: Fifteen consecutive patients with dermatitis herpetiformis taking dapsone therapy received, in addition, 800 U/d of vitamin E for 4 weeks; then 1000 mg of vitamin C per day for 4 weeks, and, finally, combined vitamin E and vitamin C therapy for 4 weeks. Hemolysis indexes were assessed at baseline and after each 4-week period. RESULTS: Statistical analysis of the results suggests that oral administration of 800 units of vitamin E daily for 4 weeks confers partial protective effect against dapsone-induced hemolysis in patients with dermatitis herpetiformis. CONCLUSION: Partial protection against dapsone-induced hemolysis by orally administered vitamin E, if confirmed as being clinically relevant by further trials, may allow clinicians to continue dapsone therapy orally in patients who develop significant hemolysis. Prophylactic vitamin E to minimize potential hemolysis at the initiation of dapsone therapy may also be appropriate. PMID- 1739300 TI - Immunofluorescence abnormalities in lichen planopilaris. AB - BACKGROUND: Lichen planopilaris is believed to be a variant of lichen planus because both diseases have similar histologic features. However, as the clinical features of the two diseases differ, we conducted immunofluorescence studies to examine the relation between the two conditions more closely. OBSERVATIONS: Direct immunofluorescence was performed on scalp lesions of seven patients with lichen planopilaris. All had abnormal linear deposits of Ig restricted to the basement membrane zone of hair follicles. The deposits consisted of only IgG or IgA in five patients (70%) and of IgG in combination with other Igs in two patients (30%). Basement membrane zone deposits of fibrin were present in only one patient (14%) and were linear in appearance. There was no staining of ovoid bodies. These immunofluorescence abnormalities differ from those associated with lichen planus where basement membrane zone deposits of fibrin are present in almost all patients, where the basement membrane zone deposits are fibrillar in appearance, and where the deposits of Ig over ovoid bodies are common. CONCLUSIONS: The different appearance and composition of abnormal deposits of immunoreactants in lichen planopilaris and lichen planus suggest that the two conditions are different diseases. PMID- 1739301 TI - Molluscum contagiosum. Ultrastructural evidence for its presence in skin adjacent to clinical lesions in patients infected with human immunodeficiency virus type 1. Military Medical Consortium for Applied Retroviral Research. AB - BACKGROUND AND DESIGN: Molluscum contagiosum in acquired immunodeficiency disease, although not life threatening, is often a marker of late-stage disease and may lead to disfiguring cutaneous lesions. Although most current therapy results in at least temporary clearing of individual lesions, lesions frequently recur and new lesions arise. Examination of hematoxylin-eosin-stained histologic sections in two patients showed changes suggestive of viral infection in the epidermis 0.5 cm and 1 cm lateral to obvious clinical lesions. These areas were clinically free of any lesions. Both routine histopathologic examination and ultrastructural examination were performed in two patients infected with human immunodeficiency virus type 1 (HIV-1) and three non-HIV-1-infected patients. RESULTS: All patients showed histologic changes diagnostic of molluscum contagiosum. In addition, the sections from HIV-1-infected patients showed areas of acanthosis, hyperkeratosis, and nuclear atypia. Electron microscopy of these areas revealed rare viral organisms in these areas. Similar acanthotic, hyperkeratotic areas were not seen in the biopsy specimens from the non-HIV-1 infected patients and no viral particles were found in the epidermis around the lesions. CONCLUSION: Viral structures consistent with molluscum contagiosum are present within the clinically normal epidermis around lesions of molluscum contagiosum in some HIV-1-infected patients. This may explain the large number of lesions seen in these patients and the difficulty in controlling the spread and recurrence of molluscum contagiosum in HIV-1-infected patients. PMID- 1739302 TI - Restrictive dermopathy. Report of two affected siblings and a review of the literature. AB - BACKGROUND: Restrictive dermopathy is a lethal genetic disorder consisting of abnormally tight skin, generalized joint contractures, distinctive facies, and pulmonary hypoplasia. Autosomal recessive inheritance has been suggested based on multiply affected siblings and some reports of parental consanguinity. This article describes two siblings with the restrictive dermopathy syndrome and reviews previously reported cases. OBSERVATIONS: Eight other cases have been reported in the literature as restrictive dermopathy. These cases have shared striking similarities in their clinical histories and phenotypes. The skin in these infants has been described as rigid and tense, with skin biopsy specimens showing a thick epidermis, thin dermis, abnormally arranged collagen bundles, and poorly developed appendages. Other prominent features are flexion contractures and craniofacial and pulmonary abnormalities. The genetic and/or developmental defects leading to the restrictive dermopathy syndrome are presently not known. CONCLUSIONS: The restrictive dermopathy syndrome is distinct and is easily differentiated from other congenital diseases such as the icthyoses and also from the clinical conditions of sclerema neonatorum and subcutaneous fat necrosis of the newborn. Recognition of this syndrome is important for determining the prognosis of affected infants and for recommending genetic counseling to affected families. PMID- 1739303 TI - Restrictive dermopathy in two brothers. AB - BACKGROUND: Restrictive dermopathy is an autosomal recessive phenotype characterized by universal tautness of skin resulting in fetal akinesia and death during the neonatal period. The clinical signs and symptoms of this uncommon disease are described in two brothers, and evidence is provided that fetal biopsy specimens obtained during the 20th week of gestational age are nondiagnostic. OBSERVATIONS: The first patient was a growth-retarded preterm boy suffering from generalized desquamation, marked joint contractures, and facial hypoplasia. Prominent light microscopic findings were hyperorthokeratosis intermingled with parakeratosis and absence of the elastic fibers in a thinned dermis. Electron microscopic examination of the epidermis revealed a lack of keratin filaments and an abnormal globular shape of the keratohyalin granules. The child died 4 days after birth. A following pregnancy resulted in birth of a preterm boy who died of the same disease within 2 hours. In the 20th week of gestational age, fetal biopsy specimens were obtained, but light and electron microscopy failed to reveal any abnormalities. CONCLUSIONS: Restrictive dermopathy is a genuine skin disease resulting in fetal akinesia that precludes a normal intrauterine development. The clinical features of this disorder are so distinctive that an on the-spot diagnosis can be established. In view of the data obtained in this case, the feasibility of prenatal diagnosis should be regarded with great caution. PMID- 1739304 TI - Perianal pseudoverrucous papules and nodules in children. AB - BACKGROUND: Pseudoverrucous papules and nodules were originally described as a reaction to irritation in association with urostomies. These changes have not been described as occurring on the perianal skin or around colostomies. OBSERVATIONS: Five children had remarkably similar-appearing papules and nodules of the perianal and suprapubic skin. The rash consisted of more than a dozen 2- to 8-mm shiny, smooth, red, moist, flat-topped, round lesions. This peculiar and striking reaction appears to be the result of encopresis or urinary incontinence. Biopsy specimens reveal reactive acanthosis or psoriasiform spongiotic dermatitis. The lesions regress when the irritating factor is removed. CONCLUSIONS: Recognition of this entity is important because pseudoverrucous papules and nodules may mimic more serious dermatoses and unnecessary workup may be initiated. Although this reaction involving perianal skin has not been reported previously, we believe it is not uncommon. PMID- 1739305 TI - The delayed postburn blister. A commonplace but commonly overlooked phenomenon. PMID- 1739306 TI - Immunodermatopathology. PMID- 1739307 TI - Spider bite with lymphangitic streaking. Brown or violin spider bite with atypical features. PMID- 1739308 TI - Indurated telangiectatic plaques. Malignant angioendotheliomatosis (MAE). PMID- 1739309 TI - Peristomal atrophic papules. Degos' disease (malignant atrophic papulosis). PMID- 1739310 TI - The incidence of malignant melanoma in New South Wales. PMID- 1739311 TI - Limitations of direct immunofluorescence. PMID- 1739312 TI - Delayed reaction to bed bug bites. PMID- 1739313 TI - Pseudomonas mesophilica cutaneous infection in an immunocompetent patient. PMID- 1739314 TI - Incidence of allergic reactions to hydrocortisone-17-butyrate in standard patch test series. PMID- 1739315 TI - Autofluorescence of clothing as an adjunct in the diagnosis of apocrine chromhidrosis. PMID- 1739316 TI - Cutis verticis gyrata and pachydermoperiostosis: demonstration with computed tomography. PMID- 1739317 TI - Lack of efficacy of the Q-switched ruby laser in the treatment of vitiligo. PMID- 1739318 TI - Parathyroid hormone-related protein in patients with malignant melanoma. PMID- 1739319 TI - Failure to prevent nicotine addition in young people with diabetes. AB - The habit of smoking is usually acquired at a young age and it is particularly undesirable in individuals with diabetes. A study was carried out to assess objectively the prevalence of smoking in young patients with diabetes and whether younger age at onset of diabetes (implying exposure to health education) reduced the incidence of smoking. Ninety nine young adults with diabetes attending the routine clinic were studied using a structured interview and assay of a urinary nicotine metabolite (cotinine). Forty eight percent of the cohort were smoking (raised urinary cotinine), although only 31% admitted to smoking. Thirty eight percent of the patients with childhood onset diabetes, 56% of the adolescent onset, and 47% of the young adult onset patients were smoking. Smoking was not related to glycaemic control or body mass index. In conclusion, smoking is common in young patients with diabetes and is often denied. Conventional health education does not appear to prevent children and adolescents with diabetes from starting to smoke. Anti-smoking policies and health education must therefore be reinforced and improved. PMID- 1739320 TI - Do doctors recognise eating disorders in children? AB - The aim of this study was to determine whether doctors recognise eating disorders in children, in particular anorexia nervosa. A group of paediatricians, general practitioners, and school medical officers was approached to participate in the study. Each was sent a questionnaire including two case vignettes of children with anorexia nervosa and questions about diagnosis and management. The response rate was 64.5%. Of 97 different diagnosis suggested, only one quarter were psychiatric or psychological. One third of the paediatricians mentioned anorexia nervosa within their differential diagnosis in both cases compared with 2% of primary care physicians. These results suggest that doctors' awareness of childhood onset eating disorders remains limited. A delay in appropriate treatment has potentially adverse consequences for prognosis. PMID- 1739321 TI - Trial of intensive compared with weekly speech therapy in preschool children. AB - Forty two preschool children referred to a speech therapy department were randomly allocated to receive intensive individual speech therapy or the more traditional once weekly approach. Boys and minority ethnic groups were referred most frequently. Speech therapy improved expression more than comprehension, as measured on Reynell scales. The mean improvements were 0.5 SDs (95% confidence intervals (CI) 0.3 to 0.7) and 0.3 (95% CI 0.1 to 0.5) respectively. There was a greater improvement in children receiving intensive compared with weekly therapy in the expression scores (0.8 SDs (95% CI 0.5 to 1.1) v 0.2 SDs (95% CI -0.1 to 0.5]. White and non-white children had similar improvements in comprehension scores but white children had greater improvement in expression scores (1.1 SDs v 0.3 SDs). This difference was seen in both therapy groups. Randomised trials are useful in the evaluation of speech therapy in children. PMID- 1739322 TI - Home parenteral nutrition in chronic intestinal failure. AB - In children with severe failure of intestinal function, intravenous nutrition is at present the only treatment able to maintain adequate nutrition for prolonged periods of time. Over the last five years we have discharged 10 patients home on parenteral nutrition for a total of 25 patient years and here the outcome of these children is presented. Of the 10 patients, one has discontinued home parenteral nutrition (HPN), seven patients remain well, one patient has recently moved to the USA, and one patient has died after major abdominal surgery. All children had either normal or an accelerated rate of growth on HPN and developmentally all have progressed well. All the children over 5 years attend normal schools. The major complication of treatment was line sepsis with an overall rate of one episode in 476 days and a total of nine central lines (five patients) have required replacement giving an average line life of 680 days. For those children unfortunate enough to suffer from severe intestinal failure, HPN is preferable to prolonged hospital treatment and offers the chance of a good quality of life with prolonged survival. PMID- 1739323 TI - A biotinidase Km variant causing late onset bilateral optic neuropathy. AB - A patient with a newly recognised variant of biotinidase deficiency presented with acute loss of vision at the age of 10 years. Progressive bilateral optic neuropathy, spastic paraparesis, and a predominantly motor type neuropathy developed over the next five years. Metabolic investigations revealed biotin depletion causing multiple carboxylase deficiency. The basic defect was a biotin recycling disorder due to a mutant biotinidase with residual activity of 4.4% assayed routinely. Biocytin excretion in urine was only slightly increased. Further investigations on plasma biotinidase revealed biphasic kinetics with two different reduced values for maximum reaction velocity (Vmax) and two for the Michaelis constant (Km), one being almost normal and the other considerably raised. In contrast to this patient, two age matched children with partial biotinidase deficiency (2.8% and 2.9% of normal), but with a normal Km for biocytin, remained asymptomatic. After six months of oral substitution with 10 mg biotin per day the coecocentral and peripheral scotomata regressed, the pyramidal signs in the lower limbs disappeared, and further progression of the motor neuropathy arrested. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease, should include biotinidase deficiency. PMID- 1739324 TI - Beta glucuronidase and hyperbilirubinaemia in breast fed infants of diabetic mothers. AB - A prospective study was performed comparing bilirubin concentrations in 10 breast fed term infants of diabetic mothers (IDM) to those of 10 breast fed normal term infants. The beta-glucuronidase concentrations in serum and breast milk were assayed in the respective mothers. Significantly higher bilirubin concentrations were noted in the IDM group. Serum and breast milk beta-glucuronidase concentrations were significantly higher in diabetic mothers as compared with those of non-diabetic mothers. We suggest that the high concentration of beta glucuronidase in breast milk of diabetic mothers is an additional important cause leading to hyperbilirubinaemia in their breast fed infants. PMID- 1739325 TI - Axillary and rectal temperature measurements in infants. AB - Rectal and axillary temperatures were measured during the daytime in 281 infants seen randomly at home and 656 at hospital under 6 months old, using mercury-in glass thermometers. The normal temperature range derived from the babies at home was 36.7-37.9 degrees C for rectal temperature and 35.6-37.2 degrees C for axillary temperature. Rectal temperature was higher than axillary in 98% of the measurements. The mean (SD) difference between rectal and axillary temperatures was 0.7 (0.5) degrees C, with a range of 3 degrees C. When used in hospital to detect high temperature, axillary temperature had a sensitivity of 73% compared with rectal temperature. This is too insensitive for accurate detection of an infant's high temperature. Rectal temperature measurement is safer than previously suggested: perforation has occurred in less than one in two million measurements. If an infant's temperature needs to be taken, rectal temperature should be used. PMID- 1739326 TI - Streptococcus associated toxic shock. AB - In the past few years, there appears to have been a change in the spectrum of disease caused by group A beta-haemolytic streptococcus (GABHS), and a toxic shock-like syndrome caused by this organism has recently been described in adults. We report four children with an acute illness characterised by rapid progression of shock, erythematous rash, multisystem organ involvement, electrolyte derangements, and desquamation who fulfil the previously established diagnostic criteria for toxic shock syndrome. Three of the children had extensive cutaneous and soft tissue infection and the fourth had peritonitis. All four developed bacteraemia. Treatment included aggressive cardiovascular resuscitation and antibiotic therapy. Although no patient died, they suffered multiple and severe complications requiring prolonged treatment and hospitalisation. Streptococcal toxic shock syndrome is a separate and clearly defined entity occurring in previously healthy children. PMID- 1739327 TI - Implantable intravenous access device. AB - The use of a fully implantable device for venous access is described in two infants with transfusion dependent haemolytic anaemia. This device is a possible improvement in the treatment of infants needing long term venous access, although doctors should be aware of the infrequent complications. PMID- 1739328 TI - Paediatric psychotherapy: a service in a general outpatient clinic. AB - The service of paediatric psychotherapy to a general paediatric outpatient clinic is described. Using techniques developed to suit paediatric patients a median of nine patients each clinic were treated. Referral symptoms resolved in a median time of four months after a median of seven sessions. This model for the management of paediatric patients with emotional and behavioural difficulties may allow an effective and efficient use of psychotherapy time. PMID- 1739329 TI - Coeliac disease and lymphangiectasia. AB - Two out of 74 children with coeliac disease demonstrated severe intestinal protein loss. In both children a serial small bowel biopsy specimen showed intestinal lymphangiectasia to be also present. Intestinal lymphangiectasia is another disorder that may be associated with coeliac disease. PMID- 1739330 TI - Positive end expiratory pressure via a portable system in thoracic dystrophy. AB - The provision of positive end expiratory pressure, via a unique portable system, in the long term management of a child with thoracic dystrophy is reported. The system uses low gas flow enabling a reduction in equipment and simplification of the circuit as compared with a standard continuous positive airways pressure system. PMID- 1739331 TI - HIV infection in children. PMID- 1739332 TI - Medium chain acyl-CoA dehydrogenase deficiency. AB - From 65 reported cases of medium chain acyl-CoA dehydrogenase deficiency, we found an average presenting age of 13.5 months and a mean age at death of 18.5 months. One quarter of patients died of a Reye-like syndrome and/or sudden infant death. In half the cases there had been at least one sibling death. Asymptomatic cases were not uncommon (12% of cases). The crises were generally induced by a prolonged fast and after a viral prodromal phase in three quarters of cases. The crises consisted of somnolence progressing to lethargy which could lead to coma. Vomiting was frequent (60% of cases). Seizures, which were found in 29% of cases, represented a bad prognosis. The physical examinations revealed frequently a variable and regressive anicteric hepatomegaly. Blood and urine analysis revealed in most instances hypoglycaemia (96% of cases) with hypoketonuria and sometimes metabolic acidosis. Hepatic and muscular cytolytic enzymes were frequently raised, as were plasma ammonia, urea, and uric acid. Plasma total or free carnitine concentrations, especially non-fasting, were diminished in most cases. Plasma saturated medium chain fatty acids and particularly unsaturated cis-4 decenoate were on the other hand raised during the crises or during fasting. Urinary organic acid analysis revealed a characteristic profile of medium chain aciduria: C6-C10 dicarboxylic acids, hydroxy acids, glycine conjugates, and carnitine conjugates. Oral loading tests with carnitine or phenylpropionate allow a precise diagnosis. The diagnosis is confirmed by specific assays in various tissues. Avoidance of prolonged fasting seems to be the mainstay of treatment. PMID- 1739333 TI - Lower oesophageal pH monitoring--a useful clinical tool. PMID- 1739334 TI - Statistics from the inside. 3. Estimation. PMID- 1739335 TI - Accidents on hospital wards. PMID- 1739336 TI - Hazard from the exposed terminals of a battery driven transport incubator. PMID- 1739337 TI - Antenatal diagnosis of inborn errors of metabolism. PMID- 1739338 TI - Parenteral lipids and free radicals in preterm infants. PMID- 1739339 TI - Treating neonatal jaundice with phenobarbitone: the inadvertant administration of significant doses of ethyl alcohol. PMID- 1739340 TI - Transient gluten intolerance. PMID- 1739341 TI - Psoriasis in childhood. PMID- 1739342 TI - Co-morbidity associated with fabricated illness (Munchausen syndrome by proxy). AB - Fifty six children who had been victims of fabricated illnesses and 82 of their 103 siblings were studied. In addition to the index fabrication, 64% of index children had had other illnesses fabricated by their mothers. Twenty nine per cent of the index children had a history of failure to thrive and 29% a history of non-accidental injury, inappropriate medication, or neglect. Seventy three per cent of the index children had been affected by at least one of these additional problems. Eleven per cent of the siblings had died in early childhood, the cause of death not being identified. Thirty nine per cent of siblings themselves had had illnesses fabricated by their mothers, and 17% had been affected by either failure to thrive, non-accidental injury, inappropriate medication, or neglect. PMID- 1739343 TI - Comparison of BCG vaccination at birth and at third month of life. AB - Tuberculosis is an important health problem in developing countries and the BCG vaccine plays an important part in preventing the disease. There are different reports about the preventive value of BCG. Some of them claim that it is satisfactory while others suggest that it provides little protection. There are also varying ideas about the optimum time to vaccinate babies, some studies suggesting that late vaccination confers a high degree of protection. This prospective controlled study has been undertaken to evaluate the value of BCG vaccine given to babies during their first three days of life versus its value when given in their third month of life. Evaluation was measured by the results of tests with purified protein derivative (PPD), by vaccine scars, that by the complications of the vaccine. It was found that BCG given at the end of the third month provides a higher rate of response and fewer complications than when given during the first three days of life. PMID- 1739344 TI - Conditions accounting for substantial time spent in hospital in children aged 1 14 years. AB - To identify the clinical conditions associated with substantial time spent in hospital by children aged 1-14 years, records of children admitted to hospital in 1975, 1979, and 1984 were studied. Analysis was by linkage of abstracts of routine records of hospital inpatient care in six districts in southern England covered by the Oxford record linkage study. The total time spend in hospital in the acute specialties each year was calculated by summing the lengths of stay of all episodes of care for each child in each year. First, admissions with long median times in hospital per child admitted were identified. These included, notably, fracture of femur and, in the later years, leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Second conditions were identified which accounted for large numbers of children with lengths of stay of five days or more. These included, in particular, congenital anomalies, asthma, and appendicitis. Third, conditions were identified which accounted for the largest numbers of bed days used. These included congenital anomalies, hypertrophy of tonsils and adenoids, asthma, otitis media, appendicitis, and head injury. Median time spent in hospital per child admitted declined for most conditions but increased for leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Admission rates for children who spent five days or more in hospital each year declined for all common conditions except asthma which increased. Total numbers of beds used increased for asthma and otitis media but declined for all other common conditions. PMID- 1739345 TI - Congenital hypothyroidism detected by neonatal screening: relationship between biochemical severity and early clinical features. AB - The relationships between biochemical severity of hypothyroidism (as judged by plasma thyroxine) and the clinical and radiographic findings at diagnosis were evaluated in 449 infants born in 1982-4 with congenital hypothyroidism identified by neonatal screening. Details of pregnancy, delivery, and the neonatal period were also examined and compared with the findings in a normal population of 36,727 infants born in 1988. Infants with plasma thyroxine values of 30 nmol/l or less had a significantly higher incidence of prolonged jaundice, feeding difficulties, lethargy, umbilical hernia and macroglossia, showed more severe delay of bone maturation on a knee radiograph, and had a higher proportion of thyroid agenesis on isotope scan. In contrast, an ectopic or hypoplastic gland was more common in infants with plasma thyroxine values above 30 nmol/l. Prevalence of illness in pregnancy and mode of delivery was not related to severity of hypothyroidism and were similar to figures for the normal population. Induction of labour, gestation over 40 weeks, and birth weight above 3500 g were significantly more common in the hypothyroid infants. Perinatal illness and congenital malformations were more common in the infants with low plasma thyroxine values at diagnosis. PMID- 1739346 TI - Relationship between urinary and serum growth hormone and pubertal status. AB - Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty. PMID- 1739347 TI - Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications. AB - Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model. PMID- 1739348 TI - Substandard monitoring of warfarin in North America. Time for change. PMID- 1739349 TI - Shepherding the patient's right to self-determination. The physician's dawning role. PMID- 1739350 TI - Who needs a preoperative electrocardiogram? PMID- 1739351 TI - A votre sante. PMID- 1739352 TI - Guidelines for medical practice and the future of medicine. PMID- 1739353 TI - Availability of primary care health personnel. The States speak out. AB - The adequacy of the supply of health personnel, and primary care personnel in particular, has been assessed at the aggregate national level and the disaggregate or regional/state perspective. While Federal programs have been successful in expanding the Nation's supply of health care practitioners and alleviating aggregate national shortages in some occupations and specialties, problems of geographic distribution remain. In an effort to obtain information on the adequacy of the supply of health care personnel within each state and jurisdiction, the chief executives were asked to assess their most pressing personnel supply concerns. The two occupations most often cited as being in short supply were primary care physicians and registered nurses. The state assessment of shortages of registered nurses is in concert with national assessments. In contrast, the supply of primary care physicians appears to be adequate if not in excess at the national level, implying that aggregate assessments may camouflage significant regional and state shortages. Disaggregate assessments are essential to derive an appropriate picture of national supply adequacy. PMID- 1739354 TI - Reliance on prothrombin time ratios causes significant errors in anticoagulation therapy. AB - BACKGROUND: The intensity of warfarin anticoagulation in the United States may be inappropriate if the international normalized ratio (INR) is not used, or if the international sensitivity index (ISI) of the thromboplastin is outside the range of 2.2 to 2.6. METHODS: Fifty-three hospital laboratories provided data on the sensitivity of their thromboplastin and whether they reported INR values. Additional data on thromboplastin sensitivity were obtained from 140 laboratories involved in the Stroke Prevention in Atrial Fibrillation study. The three major manufacturers of thromboplastin confirmed the range of thromboplastin sensitivity reported by the laboratories. RESULTS: Of 53 laboratories surveyed, 16 (30%) could not provide ISI data and only 11 (21%) reported INR results. Unlabeled thromboplastin was being used by 20% to 24% of laboratories, and only 8% to 20% were using thromboplastins with an ISI of 2.2 to 2.6. At the time the three manufacturers were contacted, they reported marketing thromboplastins with ISI values from 1.2 to 2.8, but none of the thromboplastins at that time had ISI values between 2.2 and 2.6. CONCLUSION: Warfarin therapy in the United States is managed inappropriately because most laboratories do not report INRs and the variability in thromboplastin sensitivity produces misleading prothrombin time ratio results. Additionally, recent research may require reexamination if INR or ISI data were not provided. PMID- 1739355 TI - A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. AB - BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer. PMID- 1739356 TI - Durable power of attorney for health care. A survey of senior center participants. AB - Fifty-nine healthy senior center participants were interviewed to determine how, when, and why the durable power of attorney for health care is being used. The 21 users of the durable power of attorney for health care executed a form for the expected reasons; however, a majority had not given a copy of the form to their physician and few had discussed details of their preferences with the proxy. Of the 38 nonusers, the most frequent reasons for not executing a durable power of attorney for health care were: lack of awareness of the form, procrastination, and difficulty choosing a proxy. The new Patient Self-Determination Act requiring hospitals to inform patients of advance directives will help to overcome some of the obstacles in use of the durable power of attorney for health care; however, community education must still be encouraged. PMID- 1739357 TI - Moderate and heavy alcohol consumption have no favorable effect on lipid values. AB - Moderate alcohol consumption has been reported to provide protection against coronary heart disease. We studied serum lipid values in 380 men, including 184 controls (37 teetotalers and 147 moderate drinkers), 90 heavy drinkers, and 106 alcoholics. Total cholesterol values were significantly lower among alcoholics than controls (mean +/- SEM, 5.43 +/- 0.15 mmol/L [210 +/- 5.8 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]), but their high-density lipoprotein (HDL) cholesterol values were higher (1.66 +/- 0.07 mmol/L [64 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). Accordingly, there was a highly significant difference in the HDL/total cholesterol ratio (0.32 +/- 0.13 vs 0.19 +/- 0.01). Heavy drinkers had significantly higher total cholesterol values than controls (6.30 +/- 0.13 mmol/L [244 +/- 5.0 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]); the same was true of HDL cholesterol values (1.25 +/- 0.07 mmol/L [48 +/ 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). No significant difference was found in the HDL/total cholesterol ratio between controls and heavy drinkers or between teetotalers and moderate drinkers. Therefore, moderate alcohol intake apparently does not change HDL/total cholesterol ratio; if moderate drinking is protective against coronary heart disease, the mechanism is probably not via lipids. PMID- 1739358 TI - The utility of preoperative electrocardiograms in the ambulatory surgical patient. AB - To determine the utility of preoperative screening electrocardiograms (ECGs) among ambulatory surgery patients, we reviewed the charts of 751 consecutive adult patients who underwent ambulatory surgery. Data were collected on demographic characteristics, coexisting medical problems, American Society of Anesthesiologists physical status score, preoperative ECG results, adverse intraoperative cardiovascular events, and postoperative cardiovascular complications. In our study population of relatively healthy outpatients, preoperative ECGs were abnormal in 42.7% of patients. Age, increased physical status score, and male gender were associated with a greater incidence of abnormal preoperative ECGs. There were 12 adverse cardiovascular perioperative events among the 751 patients (1.6%), and the preoperative ECG may have been clinically useful in six of these 12 patients. Neither preoperative ECGs nor results of preoperative screening questionnaires were predictive of adverse cardiovascular perioperative events. These findings question the utility of preoperative ECGs in the ambulatory surgery setting, especially among younger, relatively healthy patients. PMID- 1739359 TI - Identification of severe coronary artery disease using simple clinical parameters. AB - The purpose of our study was to examine the ability of clinical and resting electrocardiographic variables to provide useful estimates of the probability of three-vessel or left-main coronary artery disease. The study group consisted of 680 patients with symptomatic coronary artery disease who underwent exercise equilibrium radionuclide angiography and coronary angiography within 6 months. Sixteen clinical and electrocardiographic variables were examined by logistic regression analysis. The independently predictive variables were then used to develop convenient graphic estimates of the probability of three-vessel or left main disease and to classify patients into high-risk (greater than 35%), intermediate-risk (15-35%), or low-risk (less than 15%) groups. Five variables were independently predictive of left-main or three-vessel disease: age, typical angina, diabetes, gender, and both history and electrocardiographic evidence of a prior myocardial infarction. A single graph was constructed that displayed the probability of severe coronary artery disease as a function of a five-point cardiac risk scale, which incorporated these variables. Two hundred sixty-two patients (39% of the study group) were classified as high risk; 127 of these patients (48%) had three-vessel or left-main disease. An additional 96 patients were classified as low risk; nine of these patients (9%) had three-vessel or left main disease. Five clinical variables that were obtained on an initial patient assessment can provide useful estimates of the likelihood of severe coronary disease. PMID- 1739360 TI - Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. AB - Adjuvant therapy for breast cancer with tamoxifen is suggested to be of benefit to both women with negative and women with positive axillary nodes, and treatment lasting several years is currently being investigated. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible mechanisms of this effect, we evaluated changes in antithrombin III levels, fibrinogen levels, and platelet counts in 140 postmenopausal women with surgically resected breast cancer who were disease free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. Antithrombin III levels, elevated at baseline evaluation, decreased in tamoxifen-treated subjects at 6 months, but no subject exhibited a drop to clinically significant levels. Fibrinogen levels decreased 15% (0.4 g/L) in tamoxifen-treated subjects at 6 months. Platelet counts decreased 7% to 9% from baseline to evaluations at 3, 6, 12, 18, and 24 months in tamoxifen-treated subjects. While these changes do not explain the possible small thrombophlebitis promoting effect of tamoxifen, the decrease in fibrinogen levels might be expected to be associated with a decreased risk of arterial thrombosis. PMID- 1739361 TI - Severity of pulmonary asbestosis as classified by International Labour Organisation profusion of irregular opacities in 8749 asbestos-exposed American workers. Those who never smoked compared with those who ever smoked. AB - The profusion of irregular opacities on chest roentgenograms by International Labour Organisation pneumoconiosis criteria was used to assess the severity of asbestosis in 8749 asbestos-exposed active and retired American workers. Seventy eight percent had no asbestosis (category 0/0 or 0/1), 18.6% had slight asbestosis (1/0 to 1/2), 3% had moderate asbestosis (2/1 to 2/3), and 0.3% had advanced disease (3/2 or greater). Significantly more current smokers had asbestosis than did those who had never smoked, and their average profusion of opacities was higher. The mean age of current smokers with asbestosis was 60 years, whereas subjects with the disease who had never smoked had a mean age of 64 years, a significant difference. Cigarette smoking and asbestosis appear to act synergistically to produce irregular opacities on chest roentgenograms of asbestos-exposed American workers. PMID- 1739362 TI - Recently acquired syphilis in the elderly population. AB - Despite the dramatic rise in syphilis incidence in the United States, studies on recently acquired syphilis in persons more than 60 years of age remain rare. Thirty-five cases of primary, secondary, and early latent syphilis in individuals 60 years and older were identified in the city of Hartford, Conn, between 1985 and 1990. There were no cases of early syphilis in the elderly reported from 1985 to 1986, whereas there were 23 cases reported from 1989 to 1990. Thirty-three cases occurred in men and two cases occurred in women; 25 patients were black, five were white, and five were Hispanic. Ten men reported having more than one sexual partner within 2 months of their diagnosis; five of these 10 had sexual relations with a prostitute. Physicians who care for the elderly should perform a complete sexual history and counsel patients regarding high-risk sexual practices. PMID- 1739363 TI - Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients. AB - We evaluated the occurrence and persistence of delirium in 325 elderly patients admitted to a teaching hospital from either a defined community or a long-term care facility. Of the study participants, 34 (10.5%) had Diagnostic and Statistical Manual of Mental Disorders, Third Edition--defined delirium at initial evaluation; of the remaining patients, 91 (31.3%) developed new-onset delirium. An additional 110 patients also experienced individual symptoms of delirium without meeting full criteria. Preexisting cognitive impairment and advanced age were associated with increased risk of incident delirium in the community sample but not the institutional one. Delirium was not associated with an increased risk of mortality, but it was associated with a prolonged hospital stay and an increased risk of institutional placement among community-dwelling elderly. Only five patients (4%) experienced resolution of all new symptoms of delirium before hospital discharge, and only 20.8% and 17.7%, respectively, had resolution of all new symptoms by 3 and 6 months after hospital discharge. These data suggest that delirium is a common disorder that may be substantially less transient than currently believed and that incomplete manifestations of the syndrome may be frequent. PMID- 1739364 TI - Factors associated with veterans' decisions about living wills. AB - Most states have adopted legislation that allows patients to designate by advance directives the type of health care they would like to receive if they should become incompetent while suffering from a terminal illness. The living will is one of the most common of these legal instruments. Unlike most studies that have examined very sick or hospitalized patients' preferences regarding life sustaining treatments, our study explores the concerns of 70 ambulatory veterans from a general medical clinic regarding living wills. Before the interview, 43% of patients reported never having heard of living wills. At interview, 4% of the patients had a living will, 33% intended to sign a living will but had not done so (INTEND), 54% were undecided about living wills (UNDECIDED), and 9% did not want a living will. Compared with UNDECIDED patients, all other patients did not differ in the use of health care services during the previous year or in diagnoses. INTEND patients, however, were significantly more likely to be white, to express poorer health status, to know someone with a living will, and to have previously discussed the topic. UNDECIDED patients were more likely than INTEND patients to report that religious beliefs about living wills affected their decision. Virtually all (91%) of the respondents believed that signing a living will would not affect their treatment. These data suggest that many patients may not know that they can have a living will and that discussions with those who already have a living will may be helpful in educational programs designed to promote informed patient decision-making. PMID- 1739365 TI - Effect of buspirone on withdrawal symptoms associated with smoking cessation. AB - BACKGROUND: Preliminary information suggests that buspirone hydrochloride ameliorates symptoms of nicotine withdrawal. In a double-blind, randomized, placebo-controlled trial, we determined the effects of buspirone on the withdrawal symptoms associated with smoking cessation in 40 long-term cigarette smokers. METHODS: Subjects were randomized to 4 weeks of treatment with either buspirone (n = 20) or placebo (n = 20). Subjects were instructed to maintain their usual cigarette intake during the first 21 days of treatment and to cease smoking on day 22 of treatment. Withdrawal symptoms were subjectively rated before and during smoking cessation. RESULTS: Before smoking cessation, there were no significant differences in the intensity of any withdrawal symptom between the buspirone- and placebo-treated subjects, with the exception of a significantly higher rating for drowsiness in the buspirone group. During the smoking cessation period, the ratings for craving, anxiety, irritability, restlessness, and sadness were significantly lower in the buspirone group than the placebo group. There were no significant differences between the groups in their ratings for hunger, inability to concentrate, or drowsiness. Fifteen buspirone-treated subjects and nine placebo-treated subjects were able to abstain from cigarettes during the entire 7-day smoking cessation period. No subject dropped out of the study for perceived drug side effects. Eight buspirone-treated subjects and five placebo-treated subjects reported side effects, all of which were mild. CONCLUSIONS: Buspirone ameliorated most of the short-term withdrawal symptoms associated with smoking cessation. Further controlled studies will be needed to define the benefit in smoking cessation. PMID- 1739366 TI - Mupirocin treatment of nasal staphylococcal colonization. AB - The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study. Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus. Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains. Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains. At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized. Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates. None of the subjects had serious adverse effects. Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated. PMID- 1739367 TI - Borderline-low serum thyrotropin level is correlated with increased fasting urinary hydroxyproline excretion. AB - BACKGROUND: Recent studies suggest that even mildly supraphysiologic thyroid hormonal status accelerates bone loss. In hyperthyroidism, increased bone resorption is the predominant mechanism for bone loss. We postulated that the changes in thyroid hormone status as reflected by low-normal and minimally subnormal serum thyrotropin level would have an effect on bone turnover and could be detected by a simple, noninvasive marker of bone resorption, fasting urinary total hydroxyproline-creatinine excretion (THP/Cr). METHODS: We retrospectively identified ambulatory patients with a restricted range of diagnoses who had had measurements of thyrotropin and THP/Cr performed within +/- 21 days. RESULTS: Of the 86 patients, 47 had thyrotropin levels greater than 1.0 mU/L. In these patients, no correlation was evident for thyrotropin and THP/Cr. Of the other 39 patients, 11 had suppressed thyrotropin levels (less than 0.1 mU/L) and showed clearly elevated values for THP/Cr, as expected from previous studies of hyperthyroidism. For 28 patients with thyrotropin in the borderline and low normal range of 0.1 to 1.0 mU/L, a significant negative correlation with THP/Cr was found. The THP/Cr was positively correlated with serum alkaline phosphatase level, as expected with increased bone turnover. CONCLUSIONS: These results add further support to the hypothesis that even a minimal excess of thyroid hormones increases bone turnover and may contribute to accelerated bone loss. PMID- 1739368 TI - Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects. AB - BACKGROUND: Responding appropriately to hypotensive challenges is an important determinant of health and functional independence in elderly individuals. Cardiovascular responses to phlebotomy and postural change were evaluated using a large database developed in a study designed to establish the safety of blood donation by older individuals. METHODS: The groups studied included 464 subjects aged 65 years and younger (range, 52 to 65 years) and 532 subjects more than 65 years old (range, 66 to 78 years old). Blood pressure and pulse rate measurements were followed by the withdrawal of 500 mL of blood. These measurements were repeated, first in the supine and then in the sitting position. RESULTS: Nearly all individuals studied remained hemodynamically stable after these two challenges. Age was not an independent predictor of blood pressure change after either phlebotomy or postural change. Large decreases in diastolic blood pressure were equally rare in both age groups. However, more older subjects (15.2%) exhibited a decline of 20 mm Hg or more in systolic blood pressure following phlebotomy, compared with the middle-aged group (6.9%). These age-related differences did not persist after controlling for the higher initial systolic blood pressures observed in the older subjects. Postphlebotomy postural change to the sitting position had little additional effect. CONCLUSIONS: These results indicate that the ability to respond to hypovolemia and postural change remains relatively intact in healthy elderly individuals. The higher prevalence of a significant drop in systolic blood pressure after phlebotomy, orthostasis, and possibly other homeostatic challenges in older subjects is probably due to the presence of higher basal blood pressure readings, including hypertension. In spite of these differences, blood donation is appropriate and should be encouraged in healthy elderly individuals in this age group. PMID- 1739369 TI - Differences in urinary albumin excretion rate between normotensive and hypertensive, white and nonwhite subjects. AB - Eighty-one normotensive and 61 hypertensive white and nonwhite subjects were studied cross-sectionally to determine the prevalence and determinants of elevated urinary albumin levels. Twenty-four-hour urinary albumin excretion was determined by radioimmunoassay. The prevalence of elevated urinary albumin level (greater than or equal to 15 mg/24 h) was significantly greater in hypertensive than in normotensive subjects (31.1% and 8.6%). Among hypertensive subjects, a much greater proportion of whites than nonwhites had urinary albumin levels of 15 mg/24 h or greater (39.5% and 17.4%). The independent association of blood pressure with urinary albumin level was affirmed by logistic regression analyses for white normotensive and hypertensive subjects combined, and for hypertensive subjects alone. Furthermore, among hypertensive subjects, whites were five times as likely as nonwhites to have elevated urinary albumin levels. Thus, blood pressure and ethnicity were the important determinants of urinary albumin excretion among hypertensive subjects. PMID- 1739370 TI - Return to work after an initial myocardial infarction and subsequent emotional distress. AB - We examined how return to work predicted subsequent change in emotional distress in 143 patients who had been employed at the time of initial myocardial infarction. Ninety patients (63%) returned to work by 4 months and remained employed at 12 months. There were no differences in mental health at baseline between those who returned to work and those who did not, but emotional distress decreased significantly between 4 and 12 months only in the group who returned to work. Emotional distress declined after resuming work even when employees returned to jobs with which they reported dissatisfaction at the time of the myocardial infarction. The relationship between return to work and decreasing emotional distress remained after controlling for initial physical and psychological adjustment as well as sociodemographic and social support characteristics. The improvements in mental health associated with return to work should reassure clinicians who emphasize the emotional as well as economic value of work after an initial myocardial infarction. PMID- 1739371 TI - Amantadine-resistant influenza A in a nursing facility. AB - Rapid index case treatment and amantadine prophylaxis were implemented in two nursing homes exposed to influenza A. Facility A had no isolation of cases, and 18 of 22 cases occurred after amantadine hydrochloride therapy was initiated. Three patients exhibited amantadine-resistant virus. Facility B had day 1 isolation of the index case. A facility-wide outbreak did not occur. The experience of these facilities suggests that concurrent amantadine treatment and prophylaxis without adequate case isolation may promote further influenza A infection in a nursing facility. PMID- 1739372 TI - Multiple-dose charcoal and whole-bowel irrigation do not increase clearance of absorbed salicylate. AB - BACKGROUND: This study assesses whether oral multiple-dose charcoal therapy (MDC) or whole-bowel irrigation (WBI) enhances the excretion of previously absorbed salicylate. METHODS: A controlled, randomized, three-limbed crossover protocol was used in nine humans who ingested aspirin. Salicylate levels were measured in serial serum specimens and 32-hour urine collections and kinetic parameters were calculated. RESULTS: There were no differences among the control (CTL), MDC, or WBI groups for area under the serum concentration vs time curve (CTL, 2320 +/- 501 mg/L.h MDC, 2040 +/- 454 mg/L.h; WBI, 2093 +/- 418 mg/L.h) or for urinary salicylates (CTL, 54.9% +/- 9.4%; MDC, 50.9% +/- 8.0%, WBI, 52.4% +/- 13.7% of ingested dose). CONCLUSIONS: Our data do not support the use of either MDC or WBI to enhance the excretion of previously absorbed salicylate in poisoned patients. In patients with drug overdoses, a clear rectal effluent remains as the endpoint for WBI. PMID- 1739373 TI - HIV antibody testing in young, urban adults. AB - We surveyed men and women aged 21 to 34 years to determine the rates of human immunodeficiency virus (HIV) antibody testing in blacks and whites of diverse education levels in four US cities. Responses to the anonymous, mailed questionnaire were received from 90% of 777 white women, 64% of 734 black women, 79% of 677 white men, and 48% of 541 black men. The percentages reporting HIV testing for these four race-gender groups were 29%, 22%, 30%, and 38%, respectively. The percentages reporting testing that was voluntarily sought (ie, not in connection with blood donation, military service) were 16%, 14%, 18%, and 22%, respectively. In each race-gender group, roughly half of those who had not been tested said they "might have a blood test for the AIDS virus in the future". Education level was not correlated with HIV-testing frequency. Blacks were significantly less likely than whites to be aware of "a blood test that can detect the AIDS virus infection" (58% vs 77%), but blacks who knew of the test were more likely than whites to have been tested (47% vs 37%). Eleven percent of subjects reported at least one major risk factor for HIV infection. In these people, HIV testing was most common among homosexually active men (56% tested; 52% voluntarily sought), intermediate among injection drug users (40% tested; 31% voluntarily sought), and least common among the sexual partners of injection-drug users (21% tested; 11% voluntarily sought). Health education programs need to communicate the availability of, and need for, anonymous HIV testing. PMID- 1739374 TI - Fluconazole in the treatment of hepatosplenic candidiasis. AB - Hepatosplenic candidiasis has increased in frequency among immunocompromised hosts. Risk factors include hematologic malignancy, intensive chemotherapy, prolonged neutropenia, and treatment with broad-spectrum antibiotics. Patients most commonly present with abdominal pain, persistent fevers despite antibiotic therapy, and an elevated alkaline phosphatase level that is out of proportion to other hepatic enzyme levels. Gastrointestinal mucosal damage secondary to intensive chemotherapy may allow colonization with Candida species and subsequent seeding of the portal vein. Treatment has consisted of prolonged courses of amphotericin B, with mortality rates approaching 50%. We report a case of hepatosplenic candidiasis in a patient with acute myelogenous leukemia who had clinical and radiographic improvement during fluconazole therapy. Fluconazole may be an efficacious and less toxic alternative to amphotericin B. PMID- 1739375 TI - An acquired hemorrhagic disorder from long-acting rodenticide ingestion. AB - A 62-year-old man who presented with gross hematuria was found to have a severe and prolonged coagulopathy. The workup involved mixing studies, which suggested an acquired factor deficiency, and specific factor assays, which demonstrated isolated defects in vitamin K-dependent factors. With vitamin K deficiency excluded, and serum warfarin levels undetectable, so-called superwarfarin ingestion was suspected. This diagnosis was subsequently proved by biochemical evidence (an increase in the serum vitamin K epoxide-vitamin K ratio) and compatible history. This case illustrates how a logical workup can lead to a diagnosis of superwarfarin ingestion, even without a history of such an ingestion. New serum assays for specific superwarfarins are also mentioned. This case report should increase clinicians' awareness of long-acting rodenticide ingestions. PMID- 1739376 TI - Anxiety disorders and hyperventilation. PMID- 1739377 TI - Vancomycin-induced cytopenias. PMID- 1739378 TI - Lowering cholesterol and death due to accidents, suicides: unresolved issues. PMID- 1739379 TI - The intensive care unit--industrial complex. PMID- 1739380 TI - A proposed mechanism of the inflammatory attacks in familial Mediterranean fever. PMID- 1739381 TI - Availability of zirconium in topical antiperspirants. PMID- 1739382 TI - National health policy without rationing? PMID- 1739384 TI - Medical database finalized. PMID- 1739383 TI - Renal cell carcinoma following prolonged testosterone therapy. PMID- 1739385 TI - IgA nephropathy: preliminary results of low-antigen-content diet treatment. PMID- 1739386 TI - Morphological and contractile characteristics of rat aortae perfused for 3 or 6 days in vitro. AB - We studied the morphological and contractile characteristics of rat thoracic aortic segments perfused for 3 or 6 days under pulsatile conditions. Light microscopic examination of the segments revealed the presence of an unchanged tunica media. However, the intimal surface was mostly devoid of endothelial cells. The perfused aortic segments showed a dramatic increase in spontaneous tone when compared to fresh and sham-treated aortic segments. Maximum responses to potassium and norepinephrine were reduced after 3 days of perfusion (20-40% reduction), while maximum responses to 5-hydroxytryptamine and angiotensin II were not significantly different. After 6 days of perfusion, maximum responses to all agonist were reduced (50-60%). Sensitivity to norepinephrine was not affected by the treatment, while sensitivity to 5-hydroxytryptamine was reduced. The perfused aortic segments relaxed well in response to isoproterenol. Our system provides a useful experimental model for short-term studies of hypertension- and atherosclerosis-related vascular changes. Further refinement and characterization could improve the performance of the system for longer-term studies. PMID- 1739387 TI - Effects of diazepam (Valium) on aortic atherogenesis and plasma lecithin: cholesterol acyltransferase activity in cockerels fed an atherogenic diet. AB - Blood plasma LCAT (lecithin: cholesterol acyltransferase, EC 2.3.1.43) was studied in cockerels fed an atherogenic diet to determine if attenuation of aortic atherogenesis, as a result of simultaneous treatment of the birds with diazepam, might be related to modulation of enzyme activity by the drug. Administration of diazepam (0.6 mg/kg) did not influence LCAT. It was observed that no relationship could be established between enzyme activity and the extent of aortic atherogenesis. In contrast, addition of diazepam in vitro to cockerel plasma caused a concentration-dependent inhibition of LCAT activity. The effect was most pronounced when diazepam was present at a concentration of 50-200 microM, where inhibition of enzyme activity was 25-65%. Thus, pharmacologic doses of diazepam do not appear to affect LCAT in vivo. It is concluded that diazepam attenuates aortic atherogenesis in cockerels fed an atherogenic diet by a mechanism independent of LCAT. PMID- 1739388 TI - Treatment of diabetic ketoacidosis and non-ketotic hyperosmolar diabetic coma. AB - Although mortality of diabetic ketoacidosis (KA) has decreased during the past 20 yr to 1-2%, hyperosmolar non-ketotic coma (HNC) is still lethal in 20-30% of cases due to severe underlying conditions or to complications. The most frequent causes of death are infections and thromboembolic disorders. The strategies of initial treatment of KA and HNC are similar; in KA, insulin, fluid and electrolyte replacement have first priority. In HNC, rehydration and electrolyte administration are of primary importance. It is now generally recognized that insulin therapy is best performed using low doses (4-8 units/h); after institution of insulin treatment and rehydration there are rapid changes of fluid and electrolytes from the extra- into the intravascular space. In this situation it is a major therapeutic challenge to avoid complications due to hypokalaemia, hypophosphataemia, hypomagnesaemia and hypovolaemia. These complications should be avoided by adequate replacement, and particularly by regular clinical and laboratory monitoring. When blood glucose concentrations decrease below 14 mmols/l, blood glucose concentrations should initially be maintained at this level because rapid lowering below this level may increase the risk of brain oedema. Too-vigorous fluid replacement with crystalline solutions also increases the risk that brain oedema or complications like the adult respiratory distress syndrome will develop. If hypovolaemia persists in spite of adequate crystalloid solutions, colloid-containing fluids such as albumin should be administered. It is not established whether replacements of phosphate and magnesium have clinical benefits. Nevertheless, it is probably justified to administer phosphate and magnesium when their serum concentrations are below the normal range, particularly if the clinical situation is critical. Mortality from diabetic coma in industrialized countries may only be decreased by prophylaxis, i.e. by education of all diabetic patients and physicians to detect metabolic decompensation early. PMID- 1739389 TI - Endocrine emergencies. PMID- 1739390 TI - Disorders of water balance--hyponatraemia and hypernatraemia. AB - Plasma sodium concentration depends on water balance, and is normally maintained in a narrow range by an integrated system involving the precise regulation of water intake via thirst mechanism and control of water output via vasopressin secretion. Anything that interferes with the full expression of either osmoregulatory function exposes the patient to the hazards of abnormal decreases or increases in plasma sodium level. Hyponatraemia is almost always due to a defect in water excretion. Increased intake may contribute to the problem but is rarely, if ever, a sufficient cause. Hypernatraemia is almost always due to deficient water intake; excessive water losses may contribute to the problem, but they are never a sufficient cause. The most dangerous and usually the most blatant clinical effects of the disturbed water balance are those involving the central nervous system. Complex adaptive mechanisms have been developed to mitigate the impact of both hypo- and hypernatraemia on brain cells. However, the same protective changes render the brain more susceptible to severe neuropathology that may arise from inappropriate treatment of these disorders. PMID- 1739391 TI - Management of disorders of calcium homoeostasis. AB - Severe hypercalcaemia may be life-threatening and requires prompt management. Whatever the cause, the aim of therapy should obviously be to eradicate the source of hypercalcaemic factors. After rehydration, which is an essential first step in the management strategy, and after evaluation of the prevailing pathogenetic mechanism, the acute treatment will be aimed at increasing urinary Ca excretion and inhibiting bone resorption. Among the various pharmacological agents, bisphosphonates appear to be the drugs of first choice, because of their efficacy and their virtual absence of side-effects. The decision to treat hypocalcaemia is determined by the extent of the symptoms and the risk of complications. The treatment of acute hypocalcaemia comprises the parenteral administration of Ca or magnesium, when magnesium deficiency can be suspected. Then, chronic hypocalcaemia may require the use of 1,25-dihydroxyvitamin D, once the replenishments of vitamin D stores have been assured. PMID- 1739392 TI - Phaeochromocytoma: diagnosis and management. AB - The incidence, symptoms, signs and differential diagnosis of phaeochromocytoma have been discussed in detail. Current methods of biochemical diagnosis and anatomical localization of the tumour have been reviewed, the appropriate pharmacotherapy and other aspects of medical management have been outlined. Also detailed herein are anaesthetic management and surgical approach, the pitfalls of drug administration in known or suspected phaeochromocytoma, and particular considerations when phaeochromocytoma is malignant or when it coexists with pregnancy. Three decades ago, the diagnosis and management of phaeochromocytoma was succinctly summarized as follows: 'think of it, confirm it, find it and remove it' (Manger and Gifford, 1977; Ross, 1962). Despite the availability of sophisticated diagnostic tests and the significant progress in management, where phaeochromocytoma is concerned, a high index of suspicion ('thinking of it') remains the physician's most valuable tool. PMID- 1739393 TI - Endocrine emergencies in pregnancy. AB - A number of endocrine conditions and emergencies have unique characteristics when present in the pregnant woman. Often the abnormal endocrine state affects both mother and fetus and the various diagnostic and therapeutic approaches have to be altered to avoid harming the fetus. Furthermore, the pregnant state itself may alter the natural course of the underlying endocrine condition. Prolactinomas may enlarge due to the hormonal milieu of pregnancy, causing mass effects and even apoplexy. Anticipation of this possibility and prompt recognition may prevent disastrous consequences. This stimulatory state may extend to the normal pituitary, resulting in Sheehan's syndrome. An acute form of Sheehan's may go unrecognized, leading to unnecessary maternal deaths. Autoimmune endocrine disorders may sometimes be exacerbated and at other times be ameliorated during pregnancy. Witness the development of lymphocytic hypophysitis during pregnancy, a condition best left alone if it can be diagnosed without surgery. Graves's disease usually improves during pregnancy but it may occasionally flare, resulting in potentially lethal thyroid storm. The various therapeutic alternatives for hyperthyroidism are very much affected by effects on the fetus. Cushing's syndrome has very bad consequences for the fetus and must be diagnosed and treated urgently, if not emergently. Phaeochromocytomas are always endocrine emergencies requiring urgent and sometimes emergent treatment. Hyperparathyroidism is usually mild, but severe hypercalcaemia can be a true endocrine emergency. Recognition of the interactions of these endocrine conditions and their specific treatments with the complicated maternal-fetal unit makes their diagnosis and treatment simultaneously both difficult and extremely rewarding. PMID- 1739394 TI - Paediatric endocrine and metabolic emergencies. PMID- 1739395 TI - Endocrine emergencies. Hypoglycaemia. AB - Hypoglycaemia is possibly the most frequent metabolic emergency, in that insulin induced hypoglycaemia is a common side-effect of treatment of a common disease. The symptoms are partly sympathetic and related to the release of catecholamines. These symptoms include sweating, tremor, palpitations, sensation of hunger, restlessness and anxiety. Other symptoms are caused by an insufficient supply of glucose to the brain, resulting in neuroglucopenia with symptoms like blurred vision, weakness, slurred speech, vertigo and difficulties in concentration. Symptom recognition is the primary and most effective defence against cerebral dysfunction which is the ultimate consequence of hypoglycaemia. Even in insulin treated diabetic patients symptom failure might occur. Patients who experience severe episodes of hypoglycaemia do not constitute a special subgroup of patients. However, near-normalization of blood glucose levels have resulted in an increase in the incidence of severe hypoglycaemia. Moreover, the threshold for hormonal counter-regulatory responses in adrenaline, growth hormone and cortisol is lowered after a period of strict metabolic control in insulin-dependent diabetic patients. The glucose level at which the patients become subjectively aware of hypoglycaemia is correspondingly reduced. Other reasons for hypoglycaemia to occur are oral hypoglycaemic agents, especially sulfonylureas which may be potentiated by other drugs. Prolonged hypoglycaemia may be seen after first-order sulfonylureas, and may indicate glucose infusion as treatment. Next to insulin and sulfonylurea, ethanol is the most common cause of hypoglycaemia. In non-diabetics, hypoglycaemia will typically develop 6-24 h after a moderate or heavy intake of ethanol by a person who has had an insufficient intake of food for 1 or 2 days. Insulin-producing tumours, insulinomas and non-islet cell tumours may also be reasons for hypoglycaemia in non-diabetics. Treatment of mild episodes of hypoglycaemia is intake of fast absorbing carbohydrates. Severe episodes can be treated with either i.v. dextrose or glucagon injected i.m. or i.v. The glycaemic response and recovery of a normal level of consciousness is 1-2 min slower after glucagon than after glucose. PMID- 1739396 TI - Endocrine emergencies. Disorders of the adrenal cortex. AB - Adrenal crisis represents the major endocrine emergency with a fatal outcome if not properly recognized and correctly treated. It can present as the first manifestation of acute or chronic primary adrenal failure. Secondary adrenal insufficiency with usually less dramatic manifestations can cause mental disturbances, electrolyte or metabolic disorders severe enough to warrant prompt correction and therapeutic intervention. This is particularly true in cases of abrupt cessation of steroid treatment, pituitary apoplexy and Sheehan's syndrome. Hyperfunction of the adrenal cortex, be it hypercorticism or hypermineralocorticism, can also require rapid treatment of electrolyte disorders and hypertension. The symptoms and differential diagnosis of these entities are described as well as their proper treatment. In order to confirm later the diagnosis, the need to secure biological samples for hormone determination before starting treatment is emphasized. PMID- 1739397 TI - Pituitary gland emergencies. AB - Emergencies in pituitary disease are not common. They can result from the failure of the pituitary gland to secrete one or more pituitary hormones, or from neuro ophthalmological symptoms due to the mass effect of an expanding hypothalamic pituitary tumour. Loss of hormone secretion, particularly ACTH and, to a lesser extent, TSH, can rapidly become life-threatening and requires urgent replacement therapy. Acute severe hypopituitarism should be vigorously treated as an emergency with a glucocorticoid preparation. Neuro-ophthalmological symptoms such as visual impairment, sudden onset of severe headache and alteration of the level of consciousness should prompt appropriate radiological investigations, since this may well call for emergency surgery. PMID- 1739398 TI - Thyroid emergencies. AB - Thyroid storm is a rapid decompensation of severe hyperthyroidism which can best be described by the three criteria of hyperthermia, tachycardia and altered mental state with severe agitation. There has to be a precipitating factor such as infection, iodine contamination, surgery or even I-131 treatment. Severe hyperthyroidism not fulfilling the criteria of thyroid storm can also be an indication for emergency treatment, particularly in the elderly with heart disease. Suppressed serum TSH and elevated free T4 levels are essential to confirm the diagnosis. When rapidly available, radioiodine uptake of the thyroid can be useful. Therapy aims at rapidly reducing the active circulating hormone pool, hypermetabolic state, tachycardia, and finally hormone synthesis. Thyroid secretion can be blocked by ioipanoic acid or ipodate while hypermetabolic state can be reduced with beta-blockers or calcium channel-blockers. Treatment of hyperthyroidism in patients with iodine contamination is a real therapeutic challenge. Myxoedema coma, a complication of severe hypothyroidism, is defined by hypothermia (rectal temperature less than 36 degrees C), bradycardia, slow mentation, precipitating factor such as infection or drug overdose, and increased serum creatine phosphokinase levels. Diagnosis of severe hypothyroidism should be confirmed by serum measurements of TSH and free T4. Treatment consists of general supporting measures including rewarming, correction of serum electrolyte disturbances, and adequate alimentation. Thyroid hormone treatment should initially be aggressive using either 300-400 micrograms of T4 or 20-40 micrograms of T3 intravenously. Cortisone therapy may be added. Patients should be under close monitoring as arrhythmias and myocardial infarction are frequent complications of myxoedema coma and/or its treatment with thyroid hormones. PMID- 1739399 TI - Emergency treatment of Graves' ophthalmopathy. AB - The ocular emergencies encountered in Graves' ophthalmopathy, namely optic neuropathy, corneal ulceration, subluxation of the globe, and severe periorbital oedema with chemosis have been discussed. Evaluation of the clinical signs and symptoms of these conditions, as well as their treatment, have been outlined. Of particular concern is the complaint of 'blurry vision' that may indicate the presence of optic neuropathy. Early recognition of this entity, with prompt referral to an ophthalmologist is important because there is an inverse relationship between duration of visual loss and efficacy of treatment. The ophthalmological evaluation of a patient with optic neuropathy may demonstrate decreased visual acuity, impaired colour perception, or an afferent pupillary defect. In addition, a visual field examination may be a helpful adjunctive test. Available therapy for optic neuropathy includes high-dose corticosteroids, supervoltage X-irradiation and orbital decompressive surgery. We have reviewed the literature concerning these modalities and outlined our approach to the treatment of optic neuropathy. In general, we recommend orbital decompression at an early stage for this condition. Another worrisome complaint is of 'eye pain'. In this case, distinction must be made between the causes that include ocular inflammation, corneal keratitis and corneal ulceration. The corneal ulceration is characterized by extreme eye pain and erythema, and may require surgical intervention. Severe ocular inflammation may respond well to a course of high dose steroids. A combination of these ocular emergencies in a patient with Graves' ophthalmology necessitates careful consideration of the available treatment options. PMID- 1739400 TI - Studies on the activation of rat liver microsomal glutathione transferase in isolated hepatocytes. AB - The mechanism of activation of microsomal glutathione transferase in isolated liver cells by diisapropylidene acetone (phorone) was investigated. Phorone (1 mM) causes a time-dependent increase (up to 2.6-fold) in the glutathione transferase activity of microsomes isolated from treated hepatocytes. Since phorone reacts with sulfhydryl groups, the possibility that this compound activated microsomal glutathione transferase directly was studied. It was found that neither the activity of the purified enzyme nor that in isolated microsomes is affected by phorone. It has been suggested [Masukawa T and Iwata H, Biochem Pharmacol 35: 435-438, 1986] that activation of microsomal glutathione transferase by phorone in vivo is mediated through thiol-disulfide interchange involving oxidized glutathione (GSSG). It is shown here that the glutathione transferase activity of isolated microsomes, which was increased by the addition of 10 mM GSSG, can be decreased to the basal level with 0.1 M dithioerythritol. Dithioerythritol, on the other hand, only marginally decreases the glutathione transferase activity in microsomes isolated from phorone-treated hepatocytes. This finding argues against a role for thiol-disulfide interchange in the activation of the enzyme by phorone. Furthermore, the glutathione depletion caused by phorone does not seem to be responsible for activation per se, since other thiol depletors [e.g. diethylmaleate (DEM)] do not affect the activity of the enzyme. Immunoblot analysis of microsomes isolated from phorone-treated hepatocytes did not reveal any partial proteolysis which might have accounted for the activation. It is suggested that activation of microsomal glutathione transferase by phorone proceeds through a mechanism which might reflect an in vivo regulation of this enzyme. Additional compounds which have been shown to activate the microsomal glutathione transferase in vivo were also tested and significant activation was obtained with 1,2-dibromoethane (1.4-fold) but not with DEM or carbon tetrachloride. Activation was also obtained with 1-chloro-2,4 dinitrobenzene (CDNB) (1.6-fold) and to a small extent with t-butyl hydroperoxide (1.2-fold). The activation by 1,2-dibromoethane and CDNB is probably mediated through covalent binding, considering the known alkylating properties of these compounds. CDNB is the first substrate shown to activate the microsomal glutathione transferase implying that electrophilic compounds which are substrates can increase the rate of their own elimination by reacting with this enzyme. In addition, activation by t-butyl hydroperoxide indicates that oxidative stress can activate microsomal glutathione transferase. PMID- 1739401 TI - 1H NMR studies of reactions of copper complexes with human blood plasma and urine. AB - Reactions of the copper complexes Cu(II)Cl2, [Cu(II)(EDTA)]2-, [Cu(II)2(DIPS)4] and [Cu(I)(DMP)2]+ (where DIPS is 3,5-diisopropylsalicylate and DMP is 2,9 dimethylphenanthroline) with human blood plasma and urine have been studied by 500 MHz 1H NMR spectroscopy, and CD spectroscopy has been used to monitor the transfer of Cu(II) onto albumin in plasma. The rate of transfer of Cu(II) from [Cu(II)(EDTA)]2- onto albumin as measured by CD (T1/2 26 min, 0.5 mM Cu, 21 degrees), was similar to the rate of Cu(II) binding to amino acids and citrate, and to the rate of formation of [Ca(II)(EDTA)]2- in plasma. Reactions of Cu(II)Cl2 and [Cu(II)2(DIPS)4] in plasma followed a similar course, but were more rapid. The latter complex also appeared to give rise to the displacement of lactate from protein binding. Reactions of copper complexes in plasma therefore involve a range of low Mr ligands as well as albumin, and the ligands play a major role in determining the kinetics of the reactions. These factors, as well as the partitioning of both complexes and displaced ligands into lipoproteins, are likely to play important roles in the molecular pharmacology of copper containing drugs. In urine, His and formate were involved in EDTA and DIPS displacement from their respective copper complexes, and peaks for free DIPS and [Ca(II)(EDTA)]2- were observed. The complex (Cu(I)(DMP)2]+ appeared to be relatively stable in both plasma and urine. PMID- 1739402 TI - Protective action of seven natural phenolic compounds against peroxidative damage to biomembranes. AB - The effects of seven phenolic compounds isolated from Salvia miltiorrhiza on peroxidative damage to liver microsomes, hepatocytes and erythrocytes of rats were studied. The results show that the seven compounds inhibited lipid peroxidation of rat liver microsomes induced by iron/cysteine and Vitamin C/NADPH. The hemolysis of rat erythrocytes induced by hydrogen peroxide was also inhibited. The degree of inhibition varied with different compounds. Among the seven compounds, the action of salvianolic acid A (Sai A) was the most potent. Therefore, the protective action of Sai A against peroxidative damage to isolated rat hepatocytes and their plasma membranes was evaluated further. Malondialdehyde (MDA) production and bleb of the surfaces of rat hepatocytes induced by iron/cysteine were prevented by Sai A. The production of MDA and the consumption of NADPH of the plasma membrane during lipid peroxidation initiated by iron/cysteine and Vitamin C/NADPH were also inhibited. The results strongly suggest that several phenolic compounds like Sai A have a protective action against peroxidative damage to biomembranes. PMID- 1739403 TI - Lactational transfer of 3,3',4,4'-tetrachloro- and 2,2',4,4',5,5' hexachlorobiphenyl induces cytochrome P450IVA1 in neonates. Evidence for a potential synergistic mechanism. AB - On the first day of lactation, material rats were treated with a single low dose of 5 mg/kg body weight of 3,3',4,4'-tetrachlorobiphenyl (TCB) or 2,2',4,4',5,5' hexachlorobiphenyl (HCB) or with a combination of both congeners. Lactational transfer of these polychlorinated biphenyls (PCBs) was found in neonates and significant increases in microsomal cytochrome P450, cytochrome b5 and in glutathione-S-transferase activity were observed. Treatment with HCB did not increase neonatal ethoxyresorufin-O-de-ethylation (EROD) activities whereas a more than 26-fold increase in EROD activity was noted in response to exposure to TCB. However, EROD activities were increased more than 65-fold in response to the combined exposure to TCB and HCB. Exposure via milk to TCB caused a significant reduction in the N-demethylation of aminopyrine, but the combined exposure to TCB and HCB produced a significant reduction in the N-demethylation of dimethylnitrosamine. Lactational transfer of either TCB or HCB reduced marginally peroxisomal enzyme activities; however, exposure to a combination of TCB and HCB resulted in the highly significant reduction in KCN-insensitive palmitoyl-CoA oxidation and acetyl-CoA oxidation. Contrary to the reduction of these enzyme activities, the specific concentrations of CYP4A1 were significantly increased when neonates were exposed to either TCB or HCB. The largest induction, however, was observed in response to the combined exposure to both PCBs. Evidence is presented to suggest an induction of CYP4A1 which may be independent of the molecular substitution pattern of the two PCBs used in our studies but on a possible mode of synergistic interaction. PMID- 1739404 TI - Cytotoxicity of ortho-phenylphenol in isolated rat hepatocytes. AB - The effects of ortho-phenylphenol (OPP) and its metabolites, phenyl-hydroquinol (PHQ) and phenyl-benzoquinone (PBQ), on isolated rat hepatocytes were investigated. Addition of OPP (0.5-1.0 mM) to cells caused a dose-dependent cell death accompanied by the depletion of intracellular levels of ATP, glutathione (GSH) and protein thiols. GSH loss correlated with the formation of oxidized GSH. In addition, PHQ and especially PBQ (both at 0.5 mM) resulted in acute cell death with rapid depletion of ATP, GSH and protein thiols, and further low doses of PBQ (10-50 microM) elicited serious impairment of mitochondrial functions related to oxidative phosphorylation and Ca fluxes in isolated liver mitochondria. These results indicate that mitochondria are a target for these compounds and that OPP is itself toxic to hepatocytes even when metabolism is inhibited. The loss of cellular GSH and protein thiols accompanied by the impairment of mitochondrial function may be the main mechanisms of cytotoxicity induced by OPP and its metabolites. PMID- 1739405 TI - Enzymology of the reduction of the potent benzotriazine-di-N-oxide hypoxic cell cytotoxin SR 4233 (WIN 59075) by NAD(P)H: (quinone acceptor) oxidoreductase (EC 1.6.99.2) purified from Walker 256 rat tumour cells. AB - 3-Amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233; WIN 59075) is a highly selective hypoxic cell cytotoxin soon to enter phase I clinical trial. The compound is thought to exert its action through a toxic one-electron reduced free radical intermediate. Preliminary data have suggested that SR 4233 may be metabolized by DT-diaphorase [NAD(P)H: (quinone acceptor) oxidoreductase (EC 1.6.99.2)] to both two- and four-electron reduced products and that this route of biotransformation may represent a bioprotection pathway. In this study, a highly purified enzyme preparation was employed in order to investigate further the metabolism of SR 4233 by DT-diaphorase and to examine the mechanism of reduction in more detail. Spectrophotometric analysis showed that SR 4233 underwent reduction by DT-diaphorase with an apparent Km of 1.23 +/- 0.27 mM and Vmax of 8.55 +/- 1.67 nmol/min/microgram protein. This reaction was inhibited completely by dicoumarol (100 microM) and partially by an antiserum raised against the purified enzyme. Characterization of the products of SR 4233 reduction by reverse phase HPLC confirmed that both two- (SR 4317) and four- (SR 4330) electron reduction products were generated, the latter being the predominant metabolite, particularly in prolonged incubations. Further experiments showed that the four electron reduction product, but not the two-electron reduction product, was also a substrate for DT-diaphorase with an apparent Km of 1.14 mM and a Vmax of 57.12 nmol/min/micrograms protein. The results presented confirm that SR 4233 is indeed a substrate for DT-diaphorase and that a mixture of two-, four- and six-electron reduced products may be formed. The possible toxicological and pharmacodynamic significance of this metabolism is discussed. PMID- 1739406 TI - Medium chain length fatty acids stimulate triacylglycerol synthesis in tissue culture cells. AB - In the presence of undecanoic acid (C11) or lauric acid (C12) the synthesis of triacylglycerols was stimulated up to 10-fold both in tumor cell lines and in normal cell lines. Monocarboxylic acids of shorter or longer chain length either had no effect at all or were less effective. The increased triacylglycerol production was demonstrated, on the one hand, by the incorporation of radiolabeled glycerol into triacylglycerols and, on the other, by the incorporation of radiolabeled monocarboxylic acids, the incorporation of all (1 14C)-labeled monocarboxylic acids (C6, C12, C16, C18) regardless of their chain length, being preferentially enhanced by C11 and C12. C12 stimulated the de novo synthesis of triacylglycerols to such a degree that a 7-fold increase in the total amount of triacylglycerols per cell was observed during the first 10 hr of incubation. After removal of C12 from the tissue culture medium levels of triacylglycerols reach initial values again within 6 hr, indicating that the stimulatory effect of C12 is dependent on its continued presence. This led to the speculation that medium chain length monocarboxylic acids might be involved in the control of triacylglycerol synthesis. PMID- 1739407 TI - Inhibition of melanogenesis by BMY-28565, a novel compound depressing tyrosinase activity in B16 melanoma cells. AB - The mechanism of a novel melanin synthesis inhibitor, BMY-28565, was studied using mouse B16 melanoma cells. This compound was active in depressing the intracellular accumulation of melanin with an IC50 of 5 microM. At dose levels causing no cytotoxicity, the melanolytic effect of this compound was correlated strongly with depression of the enzymatic activity of tyrosinase (monophenol oxygenase, EC 1.14.18.1), the key enzyme in the melanin synthesis pathway. Transcription of the tyrosinase gene was not inhibited by BMY-28565, as determined by RNA blotting analysis. BMY-28565 and three other active derivatives of this compound caused increased glycosylation of proteins in B16 melanoma cells, as assessed by radioactive mannose incorporation. It is, thus, suggested that the mechanism of inhibition of tyrosinase might be related to modifications of the sugar moiety of this enzyme or of a protein(s) that is essential for the expression of its enzymatic activity. PMID- 1739408 TI - Substrate specificity of human deoxycytidine kinase toward antiviral 2',3' dideoxynucleoside analogs. AB - Deoxycytidine (dCyd) kinase has been purified to homogeneity from human leukemic spleen, and the capacity of the enzyme to phosphorylate 2',3'-dideoxynucleoside (ddN) analogs that are clinically effective inhibitors of human immunodeficiency virus (HIV) replication was evaluated. Cytosine-containing ddN analogs, such as 2',3'-dideoxycytidine, 2',3'-dideoxy-2',3'-dehydrocytidine, and cytallene, were efficiently phosphorylated by dCyd kinase, while no phosphorylation of purine containing ddN analogs was detected. dCyd kinase was completely inactive toward 2',3'-dideoxyadenosine (ddAdo), 2',3'-dideoxyinosine, 2',3'-dideoxyguanosine, and adenallene, although it was capable of phosphorylating both 2'-deoxyadenosine (dAdo) and 2'-deoxyguanosine (dGuo). The abilities of wild type and mutant human T lymphoblastoid CEM cells to accumulate ddAdo in situ and in vitro were also ascertained. Comparison of the abilities of intact wild type CEM cells and derivatives deficient in nucleoside transport, dCyd kinase, and/or adenosine (Ado) kinase to accumulate [3H]ddAdo-derived radioactivity revealed no significant differences among the wild type and mutant strains. However, ddAdo phosphorylating activity was decreased in extracts from Ado kinase-deficient cells but not in lysates prepared from cells genetically deficient in dCyd kinase activity. In comparative growth rate experiments, wild type, nucleoside transport deficient, and dCyd kinase-deficient CEM cells were equally sensitive to ddAdo toxicity, while, interestingly, a deficiency in Ado kinase correlated with a 5 fold decreased growth sensitivity to the purine ddN. Insertion of an adenine phosphoribosyltransferase deficiency into the CEM cell lines did not influence ddAdo toxicity or incorporation rate. These results imply that Ado kinase may be an important factor in ddAdo phosphorylation by CEM cells. Furthermore, these studies demonstrate that cytosine- and purine-containing ddNs are transported and activated by independent pathways and, therefore, have important implications for anti-HIV therapy in that pyrimidine and purine ddNs might be used in combination for the treatment of acquired immunodeficiency syndrome. PMID- 1739409 TI - Enzymic N-demethylation reaction catalysed by red blood cell cytosol. AB - Red blood cell cytosol promotes enzymic N-demethylation reactions which display typical Michaelis-Menten kinetics with respect to N-methylaniline as substrate. The demethylase activity is linked with hemoglobin (Hb) and is enhanced in the presence of NADH and the NADH-methemoglobin reductase system. It has been adduced that Hb in its oxygenated form is involved in the reaction. PMID- 1739410 TI - Interaction of phomopsin A with porcine brain tubulin. Inhibition of tubulin polymerization and binding at a rhizoxin binding site. AB - Phomopsin A is an antimitotic cyclic peptide containing a 13-member ring including an ether linkage. It was isolated from the fungus Phomopsis leptostromiformis as the causal agent of lupinosis. Phomopsin A strongly inhibited microtubule assembly (IC50: 2.4 microM). Our study using radiolabeled phomopsin A, prepared biosynthetically by feeding L-[U-14C]isoleucine to the culture of P. leptostromiformis, indicated that at least two binding sites of phomopsin A exist on tubulin on the basis of a Scatchard analysis; i.e. the dissociation constants of a high affinity site (Kd1) and a low affinity site (Kd2) at 37 degrees were determined to be 1 x 10(-8) and 3 x 10(-7) M, respectively. Phomopsin A inhibited the binding of radiolabeled rhizoxin to tubulin with an inhibition constant (Ki) of 0.8 x 10(-8) M. This showed that the high affinity site of phomopsin A is identical to the rhizoxin binding site. The binding of the radiolabeled phomopsin A was also inhibited by rhizoxin and ansamitocin P-3, with an inhibition constant of 10(-7) M, and to a lesser extent by vinblastine. Phomopsin A had no inhibitory effect on colchicine binding to tubulin. PMID- 1739411 TI - Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. AB - Primary steps in the metabolism of caffeine and theophylline are cleavage of methyl groups and/or hydroxylation at position 8, mediated by cytochromes P450. V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450IA1, P450IA2 and P450IIBI and human P450IA2 and rat liver epithelial cells expressing murine P450IA2 were used to overcome problems arising in the proper allocation of metabolic pathways to specific isoforms by conventional techniques. These cell lines were exposed to caffeine and/or theophylline, and concentrations of metabolites formed in the medium were determined by HPLC. Caffeine was metabolized by human, rat and murine P450IA2, resulting in the formation of four primary demethylated and hydroxylated metabolites. However, there were differences in the relative amounts of the metabolites. The human and the mouse P450IA2 isoforms predominantly mediated 3 demethylation of caffeine. The rat cytochrome P450IA2 mediated both 3 demethylation and 1-demethylation of caffeine to a similar extent. Theophylline was metabolized mainly via 8-hydroxylation. All cell lines tested were able to carry out this reaction, with highest activities in cell lines expressing rat or human P450IA2, or rat P450IA1. These results support the hypothesis that caffeine plasma clearance is a specific in vivo probe for determining human P450IA2 activity. PMID- 1739412 TI - Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake. AB - In order to investigate the effect of carbohydrate intake on ethanol-induced lipid peroxidation and cytotoxicity, rats were maintained on four different test diets, a medium-carbohydrate (carbohydrate intake, 8.4 g/day/rat on average), a low-carbohydrate (carbohydrate intake, 2.8 g/day/rat on average), an ethanol containing medium-carbohydrate (carbohydrate and an ethanol intake, 8.4 and 2.9 g/day/rat on average, respectively), and an ethanol-containing low-carbohydrate diet (2.8 and 2.9 g/day/rat on average, respectively). Ethanol and the low carbohydrate diet each increased the liver malondialdehyde content, but the combined effect of both (ethanol-containing low-carbohydrate diet) was much more prominent than either alone. The degree of increase in malondialdehyde content almost paralleled the activity of the microsomal ethanol oxidizing system. Both the low-carbohydrate and the ethanol-containing low-carbohydrate diets decreased the liver glutathione content, but ethanol combined with the medium-carbohydrate diet had no effect on the content. Ethanol treatment increased the liver triglyceride content only when combined with the low-carbohydrate diet. The rate of NADPH-dependent microsomal malondialdehyde formation was much higher in microsomes from rats maintained on the ethanol-containing low-carbohydrate diet than in those from rats on the ethanol-containing medium-carbohydrate diet, indicating that lowered carbohydrate intake augments ethanol-induced malondialdehyde accumulation in the liver by enhancing the rate of lipid peroxidation. In addition, when incubated with red blood cells in the presence of NADPH, microsomes from rats fed the ethanol-containing low-carbohydrate diet caused marked hemolysis, which was prevented by the addition of 5 mM glutathione to the incubation system. Furthermore, addition of 50 mM ethanol to the reaction system greatly accentuated the hemolysis. These results suggest that lowered carbohydrate intake at the time of ethanol consumption potentiates ethanol cytotoxicity by enhancing ethanol-induced lipid peroxidation. PMID- 1739413 TI - A comparative study on the contribution of cytochrome P450 isozymes to metabolism of benzene, toluene and trichloroethylene in rat liver. AB - The contribution of P450IIE1, P450IIC11/6, P450IIB1/2 and P450IA1/2 to the formation of chloral hydrate (CH) from trichloroethylene (TRI) was investigated in microsomes from control, ethanol-, phenobarbital (PB)- and 3 methylcholanthrene (MC)-treated rats using monoclonal antibodies (MAbs) to the respective P450 isozymes, and compared with their roles in benzene and toluene metabolism. Anti-P450IIE1 inhibited the formation of CH from TRI more strongly in microsomes from ethanol-treated rats than in microsomes from control rats at low concentration of TRI when net inhibition was compared. Anti-P450IIC11/6 inhibited CH formation in microsomes from control and PB-treated rats at high, not low, concentration of TRI, but the net inhibition in control microsomes was less than that due to anti-P450IIE1. Anti-P450IIB1/2 and anti-P450IA1/2 also inhibited CH formation from TRI in microsomes from PB- and MC-treated rats, respectively, stronger at high substrate concentration than at low concentration. These results indicate that P450IIE1, P450IIC11/6, P450IIB1/2 and P450IA1/2 are involved in the metabolic step from TRI to CH, and the first isozyme may be a low-Km TRI oxidase and the others high-Km one. Comparing the contributions of four isozymes to benzene, toluene and TRI metabolism, all four acted in the metabolism of these compounds, but P450IIE1 did not catalyse o-cresol formation nor P450IA1/2 benzyl alcohol formation from toluene, suggesting regioselectivity of toluene metabolism in the action of these two isozymes. The contribution of P450IIE1 in benzene and TRI oxidation was greater than that of P450IIC11/6, but the reverse was seen with respect to benzyl alcohol formation from toluene, indicating that P450IIC11/6 is relatively inactive towards benzene and TRI oxidation, but is primarily involved in toluene metabolism. P450IIB1/2 and P450IIC11/6 attacked all the metabolic positions studied, but only in the side-chain metabolism of toluene was their contribution significant, suggesting that these two isozymes are quite similar in function. PMID- 1739414 TI - Selective modulation of glutathione in mouse brain regions and its effect on acrylamide-induced neurotoxicity. AB - Selective modulation of brain glutathione (GSH) may assist the elucidation of the role of GSH in the central nervous system. Subcutaneous administration of diethyl maleate (DEM) depleted both cerebral and hepatic GSH in a dose- and time dependent manner. While hepatic GSH levels returned to control levels 6 hr after DEM administration, brain GSH levels remained significantly lowered for up to 12 hr after administration of DEM. However, intrathecal administration of DEM resulted in a selective lowering of brain GSH without altering hepatic levels. Intrathecal administration of L-buthionine sulfoximine (L-BSO; 1.0 mmol/kg body wt) also depleted the GSH content of the brain and the levels remained low 24 hr after L-BSO administration. The extent of GSH depletion varied in different regions of the brain; maximal depletion was observed in the brainstem, followed by the cerebellum, striatum, cortex and hippocampus. Intrathecal administration of L-2-oxothiazolidine 4-carboxylate (OTC) resulted in a marginal elevation of GSH levels in the brain. There was considerable regional variation. A maximal elevation of 134% was seen in the hippocampus, 6 hr following the intrathecal administration of 8.0 mmol of OTC/kg body wt. The effect of the modulation of brain GSH levels on acrylamide (ACR)-induced neurotoxicity was examined. Depletion of GSH by pretreatment of mice with L-BSO or DEM (administered intrathecally) enhanced the toxicity of ACR as measured by the inhibition of brain glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. The inhibition of GAPDH by ACR was attenuated by pretreatment of animals with OTC. Thus, brain GSH may play an important role in the detoxification of xenobiotics, in situ within the central nervous system. PMID- 1739415 TI - The effect of budesonide and triamcinolone acetonide on hepatic microsomal testosterone metabolism in the rat. AB - The hepatic microsomal metabolism of testosterone was studied in male rats after treatment with either budesonide or triamcinolone acetonide for 13 weeks. The in vitro metabolism was determined using a testosterone concentration of 35 nM which is comparable to the levels found in plasma. It was shown that the total microsomal testosterone metabolism was decreased in budesonide-treated rats and increased in rats treated with triamcinolone acetonide. The testosterone metabolites produced were measured and thus it was revealed that budesonide treatment brought about its effect through a 50% decrease in the activity of steroid 5 alpha-reductase, but did not affect other reductive enzymes, or the oxidation of testosterone. Triamcinolone acetonide treatment decreased steroid 5 alpha-reductase activity by 95% and also decreased the activities of steroid 3 alpha- and 3 beta-reductases by more than 90%. In addition, treatment with triamcinolone acetonide caused a 50% increase in the oxidative metabolism of testosterone, which resulted in the observed increase in total testosterone metabolism. The presence of 0.1 microM budesonide in the microsomal incubations was without effect on testosterone metabolism. However, 0.1 microM triamcinolone acetonide inhibited testosterone oxidation by 65%, without affecting the reductive pathway of testosterone metabolism. PMID- 1739416 TI - The mechanism of action and mode of inhibition of dihydroorotate dehydrogenase. A quantum chemical study. AB - Semiemperical quantum chemical calculations have been applied to study the reaction mechanism and mode of inhibition of dihydroorotate dehydrogenase. The structure of substrate, intermediate, product and various inhibitors of dihydroorotate dehydrogenase were optimized using MNDO method and the geometry, heat of formation and the net atomic partial charges of optimized molecules, as well as the energy of the reaction path were calculated. This study shows that the carbanion intermediate of this reaction is rather stable (heat of formation = -134.5 kcal) and readily forms upon nucleophilic attack by groups such as hydroxyl ion. There is good correlation between electronic properties and the biological activities of various inhibitors of this enzyme and the geometry of the most active inhibitor resembles closely that of the intermediate of the reaction. Therefore, it is concluded that the enzymatic oxidation of dihydroorotate dehydrogenase proceeds via formation of an intermediate and the inhibitors bind to the active site of this enzyme in the place of this intermediate. PMID- 1739417 TI - Effect of anthelmintics on the antioxidant system of Nippostrongylus brasiliensis. AB - To understand the mode of anthelmintic action of thiabendazole and methyl-[5-[[4 (2-pyridinyl)-l-piperazinyl]carbonyl]-1H-benzimidazole- 2-yl] carbamate (C.D.R.I. compound 81/470) against Nippostrongylus brasiliensis, their effect on the metabolism of reactive oxygen species in the parasite as well as in rat intestine was examined. Both drugs produced a significant depression in the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) of the parasite. Release of antioxidant enzymes by the drug-treated worms was also found to be appreciably lowered. Both thiabendazole and compound 81/470 induced a depression in the levels of all five constituents of the antioxidant system of rat intestine but significant alterations were detected only in the GSH content of infected and the SOD activity of normal intestine. The production of O2- by treated intestine was, on the other hand, markedly enhanced. Increased formation of O2- by the host intestine accompanied with the reduced level of SOD and GSH in N. brasiliensis appear to have a deleterious effect on the parasite. Consequently, the drug treated worms are unable to retain themselves in situ and are ultimately expelled. The greater effect produced on these parameters by thiabendazole compared to compound 81/470 is consistent with the relative efficacy of these anthelmintics. PMID- 1739418 TI - Irreversible inhibition of thromboxane (TX) A2 synthesis by Y-20811, a selective TX synthetase inhibitor. AB - As Y-20811, sodium (+-)-4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5 dimethylb+ ++ enzoic acid, has been reported to inhibit serum thromboxane (TX) A2 production with a long duration of action, its mechanism of action was investigated. When [3H]Y-20811 (3 mg/kg) was administered orally to rats, the peak platelet concentration of Y-20811 was obtained 1 hr after the administration, and the T1/2 was 43 hr. The peak plasma concentration of Y-20811 was also obtained 1 hr after administration, but the elimination of Y-20811 from plasma was faster (T1/2 alpha = 1.5 hr, T1/2 beta = 15 hr) than that observed in platelets. Serum TXA2 (estimated as TXB2) production was inhibited significantly from 1 to 72 hr after the oral administration of unlabeled Y-20811 (3 mg/kg), which temporally resembled the change of the platelet Y-20811 concentration. In platelet-rich plasma, [3H]Y-20811 completely inhibited TXA2 production at about 1500 pg/10(9) platelets, and the IC50 level was about 600 pg/10(9) platelets, which was similar to values obtained in ex vivo studies. In addition, inhibition of TXA2 production by Y-20811 still remained after washing the drug-pretreated microsomes, whereas that of dazoxiben completely disappeared. A similar irreversible inhibition of TXA2 production was observed with aspirin. These results suggest that Y-20811 may firmly combine with platelet TX synthetase and may irreversibly inhibit TXA2 production. PMID- 1739419 TI - Inhibition of a type B monoamine oxidase inhibitor, (E)-2-(4-fluorophenethyl)-3 fluoroallylamine (MDL-72974A), on semicarbazide-sensitive amine oxidases isolated from vascular tissues and sera of different species. AB - (E)-2-(4-Fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been discovered recently to be a very potent and highly selective type B monoamine oxidase inhibitor. We have found that this inhibitor is also capable of inhibiting semicarbazide-sensitive amine oxidases (SSAOs) obtained from vascular tissues and sera of different species. The inhibition of SSAO by MDL-72974A was irreversible and time dependent. It was competitive without preincubation of the enzyme with the inhibitor and demonstrated a mixed-type of inhibition when the enzyme was preincubated with the inhibitor. The IC50 values were estimated to be 2 x 10(-9) M, 5 x 10(-9) M, 8 x 10(-8) M and 2 x 10(-8) M for SSAO from dog aorta, rat aorta, bovine aorta and human umbilical artery, respectively. SSAO obtained from bovine serum was relatively insensitive to MDL-72974A (IC50 = 3 x 10(-7) M. Following intraperitoneal administration of MDL-72974A, rat brain MAO-B was inhibited with the ED50 value being about 0.2 mg/kg. Rat aorta SSAO was also inhibited and to a similar extent by the same dose. MDL-72974A is the most potent SSAO inhibitor that has been described thus far. PMID- 1739420 TI - Purification of the human blood platelet thromboxane A2/prostaglandin H2 receptor protein. AB - The human platelet thromboxane A2/prostaglandin H2 receptor has been purified 6100-fold to apparent homogeneity by a three-step chromatographic procedure with an overall yield of 6%. A 6-fold purification of the receptor was first achieved by chromatography of 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate (CHAPS)-solubilized membrane proteins from human platelets on a diethylaminoethyl (DEAE)-Sepharose column. The DEAE eluate fractions containing receptor activity were then applied to a newly developed affinity column using the cyclohexyl derivative of SQ30,741 (SQ31,491) as the immobilized ligand. Elution of the receptor from the affinity column with BM13.177 yielded a further purification of 1700-fold. An additional 4-fold receptor purification from the affinity column eluate was achieved by HPLC using GPC 500 and GPC 100 columns connected in tandem. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of the HPLC eluate containing purified receptor revealed a single, distinct band with a molecular weight of 55,000. The receptor binding activity was detected with [3H]SQ29,548 using a newly developed binding assay which involved immobilization of the receptor on polyethyleneimine-treated glass fiber filters. The binding of [3H]SQ29,548 to the purified receptor was time dependent, saturable, reversible and highly specific. Unlabeled SQ29,548, BM13.505, and U46619 (but not thromboxane B2 or 6-keto prostaglandin F1 alpha) competed for [3H]SQ29,548 binding to the purified receptor in a concentration-dependent manner. Scatchard analysis of [3H]SQ29,548 binding to the purified receptor revealed the presence of a single class of high-affinity binding sites, with a Kd of 4 nM and a Bmax of 17 nmol/mg protein. PMID- 1739421 TI - Effect of etomoxiryl-CoA on different carnitine acyltransferases. AB - The effects of etomoxiryl-CoA on purified carnitine acyltransferases and on carnitine acyl-transferases of rat heart mitochondria and rat liver microsomes were determined. At nanomolar concentrations, the data agreed with that of other investigators who have shown that etomoxiryl-CoA must be binding to a high affinity site with specific inhibition of mitochondrial carnitine palmitoyltransferase (CPTo). Micromolar amounts of etomoxiryl-CoA inhibited both short- and long-chain carnitine acyltransferases. The concentrations of etomoxiryl-CoA required for 50% inhibition of the different carnitine acetyltransferases and microsomal and peroxisomal carnitine octanoyltransferase were in the low micromolar range. Mixed-type and uncompetitive inhibition kinetics were obtained, depending on the source of purified enzyme. When purified rat heart CPT was incubated with etomoxiryl-CoA, it increased the K0.5 and decreased the Hill coefficient for acyl-CoA. Both proteins and phospholipids of mitochondria and microsomes formed covalent adducts of [3H]etomoxir, with the predominant labeling in phospholipids. None of the purified enzymes formed covalent adducts when incubated with [3H]etomoxiryl-CoA, in contrast to intact mitochondria or microsomes. The major 3H-labeled protein for rat heart mitochondria had a molecular weight of 81,000 +/- 4000, and the major proteins from microsomes had a molecular weight of 51,000-57,000. Malonyl-CoA prevented most of the tritum incorporation into the 81,000 Da protein of mitochondria, but it had little effect on incorporation of tritiated etomoxir into the 51,000 57,000 Da proteins of microsomes. When 50 microM etomoxiryl-CoA was added to microsomes and to mitochondria that had been incubated with radioactive etomoxiryl-CoA, much of the radioactive etomoxir disappeared from the major microsomal proteins, but virtually none was displaced from the mitochondrial protein. Thus, at least two different types of covalent etomoxir complexes were formed. This pulse-chase experiment showed that the mitochondrial protein etomoxir complex was not turned over, consistent with other data showing that etomoxir inhibited carnitine palmitoyltransferase. In contrast, the major protein etomoxir complex in microsomes was turned over during the pulse-chase experiment. PMID- 1739422 TI - Biochemical characterization of coumarin 7-hydroxylase activity in chick embryo liver microsomes. AB - Coumarin occurs naturally in the diet and can induce and inhibit cytochrome P450 enzymes. Hepatic coumarin 7-hydroxylase activity is the major pathway for coumarin metabolism in humans but not in rats, most strains of mice, or other laboratory animals. Coumarin 7-hydroxylase activity and the effects of chemical inhibitors and inducers on this activity were studied in 19-day-old chick embryo liver microsomes. Activity was between 35 and 75 nmol/mg protein/hr which is approximately 2-fold higher than reported for human liver microsomes. The pH optimum was 7.8 and the Km determined by both an ether extraction and a high performance liquid chromatography method was 7.3 +/- 0.9 (+/- SD) microM. Substrate inhibition was evident at coumarin concentrations above 250 microM (activities at 1000 and 4000 microM coumarin were 84 and 40% of Vmax, respectively). The Ki values (+/- SD) for inhibitors of microsomal coumarin 7 hydroxylase activity in vitro were: alpha-naphthoflavone, 46.9 +/- 19.8 nM; metyrapone, 0.8 +/- 0.9 microM; aniline, 12.3 +/- 8.2 microM; cimetidine, 70.9 +/ 27.9 microM; N-nitrosodimethylamine, 0.7 +/- 0.9 mM; and dimethyl sulfoxide, 7.9 +/- 1.9 mM. Treatment of chick embryos with pyrazole (40 mumol) increased coumarin 7-hydroxylase by 50% at 24 hr, but this activity was unaffected by treatment of embryos with 3-methylcholanthrene (2 mumol) or glutethimide (8 mumol). Thus, hepatic coumarin 7-hydroxylase activity in 19-day-old chick embryos is higher than in most laboratory animals and has similar biochemical properties as the enzyme in humans and mice. The chick embryo liver may be a useful system for studies on the biochemical effects of coumarin and the regulation of cytochrome P450-dependent coumarin 7-hydroxylase. PMID- 1739423 TI - Increased sterigmatocystin-induced mutation frequency in Saccharomyces cerevisiae expressing cytochrome P450 CYP2B1. PMID- 1739424 TI - In vitro inhibition studies of the glucuronidation of 3'-azido-3'-deoxythymidine catalysed by human liver UDP-glucuronosyl transferase. PMID- 1739425 TI - B-G: we know what it is, but what does it do? AB - B-G molecules are polymorphic cell surface proteins that are encoded by the chicken MHC. Here, Jim Kaufman and Jan Salomonsen briefly summarize developments in the molecular genetics, the structure and the tissue distribution of B-G molecules, and discuss possible functions of this intriguing multigene family. PMID- 1739426 TI - The immune system evolved to discriminate infectious nonself from noninfectious self. AB - Here, Charles Janeway argues that the requirement for two signals to initiate the adaptive immune response may reflect the evolutionary history of host defences. Early phases of host defence involve receptors and ligands that may have controlled immune responses prior to the development of clonally-distributed receptors encoded in rearranging genes. The former receptors persist in contemporary vertebrates both to trigger innate or nonclonal responses and to signal to lymphocytes that a particular antigen is associated with a microorganism. PMID- 1739427 TI - Germinal centres in T-cell-dependent antibody responses. AB - For more than a century follicles have been recognized as a site of intense cell proliferation and cell death. At last the significance of this activity is beginning to emerge: antigen-driven B-cell proliferation, somatic mutation, positive and negative selection, and memory and plasma cell development all appear to take place within the follicle. PMID- 1739428 TI - Helix-loop-helix proteins in the regulation of immunoglobulin gene transcription. AB - Transcriptional control of the Ig heavy chain and kappa light chain is dominated by single enhancers located within the body of each gene. These enhancers bind distinct, yet overlapping, sets of cell-type-specific and ubiquitous nuclear proteins. This review focuses on one particular subclass of enhancer-binding protein, termed helix-loop-helix (HLH) proteins, describing their role in the establishment of cell-type-specific transcription and suggesting how they may be regulated during B-cell maturation. PMID- 1739429 TI - Science training for European journalists. PMID- 1739430 TI - HIV and idiotypic T-cell regulation: another view. PMID- 1739431 TI - Progress in primary immunodeficiency. AB - Clinically, primary immunodeficiencies can be grouped into several well-defined syndromes. This consistent clinical picture, however, belies the enormous complexity of lymphocyte maturation and activation, and it has long been suspected that numerous distinct underlying defects give rise to primary immunodeficiencies. At a recent workshop, the molecular and genetic characterization of a handful of such defects provided tacit support for such suspicions. PMID- 1739432 TI - Primary structure and characterization of the precursor to human pituitary adenylate cyclase activating polypeptide. AB - Human cDNAs encoding the precursor to pituitary adenylate cyclase activating polypeptide (PACAP) were cloned from human testis and cerebral cortex cDNA libraries. Nucleotide sequencing revealed that cDNA from the testis library encoded the entire precursor for PACAP, while cDNA from the brain library represented only the carboxy-terminal half of the precursor. The predicted human PACAP precursor consisted of 176 amino acid residues and was very similar to the ovine one (82%). Both human and ovine precursors contained both PACAP and another peptide, PACAP-related peptide (PRP), having 29 amino acids. PACAP and PRP were preceded and followed by paired basic amino acids, recognized as important for post-translational processing. The PACAP precursor resembles the vasoactive intestinal peptide (VIP) precursor, which contains VIP and peptide histidine methionine/isoleucine amide (PHM/PHI). Structurally, PRP had some similarity to PHM/PHI, growth hormone-releasing hormone (GRH) and PACAP. Northern blot analysis indicated that a 3.0-kb transcript was expressed in the ovine hypothalamus. Tissue distribution of PACAP mRNA was also clarified in the rat. Southern blot analysis of human genomic DNA gives single bands with six restriction enzymes, indicating that a single copy of the PACAP gene is contained in a haploid genome. The cDNA for human PACAP precursor was expressed using COS-7 and Chinese hamster ovary (CHO) cells. Immunoreactive PACAP was secreted into the culture media of both transfected cell lines. PMID- 1739433 TI - The mouse intestinal fatty acid binding protein gene: nucleotide sequence, pattern of developmental and regional expression, and proposed structure of its protein product. AB - The rat intestinal fatty acid binding protein (I-FABP) gene has been used as a model to study temporal and spatial differentiation of the gut epithelium while its protein product has been used as a model for examining the atomic details of noncovalent fatty acid-protein interactions. We have isolated the mouse I-FABP gene (Fabpi) and determined its nucleotide sequence. Comparisons of the orthologous mouse, rat, and human I-FABP genes revealed three conserved domains in their otherwise divergent 5' nontranscribed sequences. RNA blot hybridization and multilabel immunocytochemical methods were used to compare the developmental stage-specific patterns of activation of the rat and mouse genes. In addition, Fabpi expression in enterocytes was examined as a function of their differentiation along the crypto-to-villus and duodenal-to-colonic axes of the small intestine. Based on the similar temporal and geographic patterns of mouse and rat I-FABP expression described here and the results of our earlier studies of transgenic mice containing rat Fabpi/human growth hormone fusion genes, we propose that one of the conserved domains, spanning nucleotides -500 to -419 in mouse Fabpi, and/or a 14-bp element, are necessary for establishing and maintaining its region-specific expression along the duodenal-to-colonic axis of the perpetually renewing gut epithelium. Finally, predictions of the structure of mouse I-FABP using the refined 2.0 A model of rat I-FABP, suggest that a proline found at position 69 of the mouse, but not rat, protein may affect its ligand binding properties. PMID- 1739434 TI - Primary structure of the ribosomal DNA intergenic spacer from the mosquito, Aedes albopictus. AB - We have determined the primary structure of a 4.7-kb portion of the ribosomal DNA intergenic spacer from cultured cells of the mosquito, Aedes albopictus. Immediately upstream from the 18S rRNA gene was a 753-bp sequence containing two regions similar to known RNA polymerase I promoters, each preceded by potential transcription termination signals. Upstream from this putative promoter region was a 3.15-kb tandem array of 17 direct repeats with a consensus sequence length of 201 bp. The 201-bp repeats contained imperfect antisense duplications of 11-bp core domain regions in the putative RNA polymerase I promoters, and sequences of possible significance in recombination. Farthest upstream of the 18S rRNA gene was an 803-bp region containing two copies each of 34-, 48-, and 64-bp elements separated by apparently unique sequence. This first detailed structural analysis of a ribosomal DNA intergenic spacer from a member of the lower Diptera has revealed features similar to those described for the higher Diptera as well as conserved motifs presumably critical to rRNA transcription. PMID- 1739435 TI - Isolation and characterization of eft-1, an elongation factor 2-like gene on chromosome III of Caenorhabditis elegans. AB - A gene (eft-1) encoding an elongation factor 2-like protein was isolated from a region adjacent to the polyubiquitin gene, ubq-1, of Caenorhabditis elegans. Sequence analysis of genomic and cDNA clones revealed that the deduced amino acid sequence of the protein (EFT-1) is 38% identical to that of mammalian and Drosophila elongation factor 2 (EF-2). The entire eft-1 gene is approximately 3.8 kb in length and contains 5 exons separated by short introns of 46-75 bp. The 2,547-bp open reading frame predicts a protein of 849 amino acid residues (calculated Mr, 96,151). Conserved sequences shared among a variety of GTP binding proteins including EF-2 are found in the amino-terminal third of EFT-1. The carboxy-terminal half contains regions with 40-57% similarity (including conservative changes) with segments characteristic of EF-2 and its prokaryotic homolog, EF-G. However, the histidyl residue target for ADP-ribosylation of EF-2 by diphtheria toxin is replaced by tyrosine in EFT-1. Southern and Northern blot analyses indicate that eft-1 is a single-copy gene that is expressed at all stages of nematode development. Amplification of fragments encoding highly conserved regions of EF-2 using the polymerase chain reaction led to the isolation of a fragment encoding the modifiable histidyl residue and which likely represents part of the C. elegans EF-2 gene (eft-2). This suggests that EFT-1 is not the C. elegans homolog of EF-2, but a closely related protein. PMID- 1739436 TI - An improved CAT assay for promoter analysis in either transgenic mice or tissue culture cells. AB - We have developed an improved method for determining CAT activity directed by stably (transgenic mice) or transiently (tissue culture cell lines) introduced CAT reporter gene constructs. The procedure is based on the use of a new buffer system which considerably increases the stability of the CAT enzyme during the preparation of the crude cell extracts. When compared to other procedures, our method enables an increase of up to 100-fold in the sensitivity of the assay, depending on the transgenic tissue tested. Furthermore, a strong increase (up to 23-fold) was also observed with various promoter/CAT constructs transiently transfected in established tissue culture cell lines. This increase in sensitivity provides a significant reduction in the time required to perform the CAT assay when strong promoters are studied (from 18 to 1 hr) and is also very useful for the analysis of CAT gene expression driven by weak promoters. PMID- 1739437 TI - Lymphedema 30 years after radical mastectomy. AB - Lymphedema is a common and often distressing consequence of the management of breast cancer. This is the first report of new onset lymphedema 30 yr after radical mastectomy for the management of breast cancer. The patient's swelling began 10 days after commencing daily finger sticks to follow blood sugar, stemming from a recent diagnosis of diabetes mellitus. If proper precautions had been observed, swelling may not have developed. The patient had marked reduction of her edema with appropriate use of graded compression garments and self administered massage therapy, after early recognition and prompt intervention into her problem. This case highlights efforts that need to be made to prevent the development of edema. PMID- 1739438 TI - A prospective study of the menstrual cycle and spinal cord injury. AB - Sixty seven menstrual cycles were studied prospectively in a nonclinical sample of 20 women who had suffered a traumatic spinal cord injury (quadriplegia n = 13; paraplegia n = 7) at least 1 yr before assessment. Level of injury did not influence cycle length (mean +/- SE = 28.7 +/- 3 days), duration of menses (4.6 +/- 1 days) or serum concentrations of gonadotropins and ovarian hormones. Midluteal phase serum progesterone values were consistent with ovulation (progesterone = greater than 5 ng/ml) in 93% of the cycles in which endocrine measures were obtained; but the ability of basal body temperature pattern to predict serum progesterone was low (43%). Cyclic dysmenorrhea was reported by 13 women with injuries ranging from C5 to T12. These findings suggest that ovulatory menstrual cycles are common in women after traumatic spinal cord injury and support the need for contraception by those wishing to avoid pregnancy. Basal body temperature charts revealed potential problems in applying the symptothermal method of natural family planning to a population of women at risk for oral contraceptives. PMID- 1739439 TI - Electromyographic and nerve conduction studies in the mdx mouse. AB - Electromyographic responses to needle-electrode insertion and repetitive indirect stimulation were recorded from gastrocnemius, soleus and cranial tibialis muscles of normal and dystrophic (mdx) mice at 20-154 days. Recordings from myotonic (ADRmto) mice served as controls for "true" myotonia. Complex repetitive discharges were observed in muscles of mdx mice but no complex repetitive discharges or other abnormalities were observed in muscles of normal control mice. Complex repetitive discharges in mdx muscles did not resemble the prolonged, abnormally repetitive discharges observed in myotonic mouse muscles. Neuromuscular blockade with tubocurarine and nerve transection had no effect on observed electromyographic abnormalities in the mdx mice. Nerve conduction and repetitive stimulation studies also revealed no abnormalities in mdx mice. These findings indicate that the mdx condition is a nonmyotonic, primary myopathy. No signs of myotonia or impaired neuromuscular transmission were found in mdx mice. PMID- 1739440 TI - Factor analysis. A methodology for data reduction in nerve conduction studies. AB - Analyzing multiple nerve conduction study parameters individually is statistically problematic. The goal of this study was to develop a useful factor analysis scheme for assessment of nerve conduction study abnormalities in diabetic neuropathy. Hypotheses were: (1) factor analysis produces a few physiologically meaningful factors, (2) there are associations between factors and markers of diabetic severity and (3) clinical impressions are related to factor scores. We studied 165 Japanese-American men: 52 nondiabetic, 66 diabetic and 47 with impaired glucose tolerance. One author (W.C.S.) obtained 28 nerve conduction study parameters in all subjects and factor analysis extracted five factors from these parameters. These factors were related to conduction velocities (factor 1), distal ulnar function (factor 2), sensory amplitudes (factor 3), distal median function (factor 4) and distal peroneal function (factor 5); together, they explain 57% of the variability in the total data. Diabetic factor scores were significantly (P less than 0.05) below that of the controls and correlations with fasting blood sugar were significant at the P less than or equal to 0.001 level. Use of this technique promises to permit sensible analysis of large amounts of data in clinical studies of diabetic and other types of polyneuropathy. PMID- 1739441 TI - Hypothyroidism producing reversible dementia. A challenge for medical rehabilitation. AB - The evaluation of dementia for reversible causes should not be overlooked. Hypothyroidism is a reversible cause for dementia. Mental status is one of the important factors to be assessed prospectively to determine whether a patient is likely to benefit from intensive inpatient rehabilitation. Because of the negative effect of dementia on the learning process during intensive inpatient medical rehabilitation, it alone may be a sufficient reason to consider alternatives to intensive inpatient rehabilitation. On our rehabilitation unit, hypothyroidism causing confusion was recognized and corrected in two patients. The thyroid-stimulating hormone test is suggested as a screening tool. PMID- 1739442 TI - Functional loading augments the initial tensile strength and energy absorption capacity of regenerating rabbit Achilles tendons. AB - The biomechanical effect of functional loading was studied in surgically tenotomized, repaired and immobilized right Achilles tendons of 34 rabbits. Beginning from the 5th day after surgery, loading was initiated by removing the immobilization casts of the animals to permit unrestricted weight-bearing to tolerance. At each of 12, 18 and 21 days after surgery, functionally loaded tendons and their corresponding nonloaded controls were excised and compared for differences in tensile strength, tensile stress and energy absorption capacity. Functional loading induced a twofold increase in the tensile strength (P less than 0.05) and energy absorption capacity (P less than 0.05) of the tendons, at both 12 and 18 days after surgery. No statistically significant differences were observed in the tensile strength and energy absorption capacity of the tendons at 21 days after surgery. Statistically significant differences in tensile stress were not observed at any time period throughout the study. These findings demonstrate that functional loading augments the tensile strength and energy absorption capacity of experimentally tenotomized tendons without promoting re rupture, but only during the very early stages of healing. Even though the healing process of rabbit tendons may differ from healing of human tendons, these results suggest that similar beneficial effects may be attained if repaired human Achilles tendon ruptures are carefully loaded during the very early rather than later stages of healing. PMID- 1739443 TI - Mechanism of unexpected death in a patient with C2 quadriplegia ventilated by aid of a phrenic nerve stimulator. Brief report. PMID- 1739444 TI - Clinical trial of a low-temperature plastic anterior ankle foot orthosis. AB - The modification of a new design in orthosis usually has its clinical indication. In this study, a low-temperature thermoplastic ankle foot orthosis (AFO) was designed in anterior leaf type, called anterior AFO, to meet the need of indoor barefoot walking in Taiwan. It could be easily molded and remolded to fit the foot, as well as to adjust the position of the foot and ankle. Sixty-eight patients with acute hemiplegia were fitted with this anterior AFO during ambulation training: 46 had good fitting (67.6%), 15 had fair fitting (22.1%) and 7 had poor fitting (10.3%). Two patients were observed to have ankle clonus, and four patients experienced breakage or tear of the AFO within 4 wk. The gait characteristics were measured in six chronic hemiplegia patients to compare the effect of anterior AFO with posterior AFO (Teufel style). Their gait pattern did improve by AFO fitting, especially from the foot pressure distribution, but no significant difference between the two types of AFO was found. PMID- 1739445 TI - Evaluation of somatic and autonomic small fibers neuropathy in diabetes. AB - The relationship between somatic and autonomic neuropathy was assessed in the feet of 30 diabetic patients. Somatic small fiber function was evaluated by the thermal threshold test for cold (A delta fibers) and warmth (C fibers). Telethermography and transcutaneous oxygen tension were used to investigate the autonomic control of peripheral circulation. Autonomic neuropathy caused the opening of arteriovenous anastomosis, which was revealed through an elevation of the feet's temperature and a low transcutaneous oxygen tension. The association of the opening of the arteriovenous anastomosis and the perturbation of the thermal threshold test established a relationship between the dysfunction of the autonomic and the somatic fibers. PMID- 1739446 TI - Intrathecal baclofen. Effects on nocturnal leg muscle spasticity. AB - Electromyographic activity was recorded from tibialis anterior during nocturnal polysomnography in six patients with severe spasticity of spinal origin. The patients had a baclofen reservoir system implanted subcutaneously into their lumbar subarachnoid space and were studied for two nights in a double-blind, placebo controlled, crossover design. Tibialis anterior electromyographic activity per hour of sleep was reduced on the night of baclofen infusion. In particular, less electromyographic activity occurred after arousal from sleep. PMID- 1739447 TI - Improving the efficiency of patient selection for continuing rehabilitation in a general hospital: the Stroke Option Rehabilitation Team. A commentary. PMID- 1739448 TI - Setting the national agenda for injury control in the 1990s: rehabilitation of persons with injuries. Special report from the Third National Injury Control Conference. PMID- 1739449 TI - Medical economics of PM&R. III. Categories of physician activities in the rehabilitation setting. PMID- 1739450 TI - Social competence: an important construct in mental retardation. PMID- 1739451 TI - Interpersonal cognitive problem-solving among children with mild mental retardation. AB - In this study we sought to determine whether interpersonal cognitive problem solving skills could distinguish adjusted from nonadjusted classroom behavior among children with mild mental retardation. Discriminant analyses indicated that, irrespective of age or IQ, adjusted children had a larger number of relevant solutions to common problems as well as a higher ratio of aggressive solutions. Findings suggest that cognitive interpersonal skills may be as important, if not even more important, for this population as for youngsters without mental retardation. PMID- 1739452 TI - Assessment of loneliness at school among children with mild mental retardation. AB - This study was designed to determine whether children with mild mental retardation understand the concept of loneliness, whether their feelings of loneliness at school can be reliably assessed, and whether there are differences in loneliness between children with and without mental retardation. Results from a sample of 62 students with mild mental retardation and 62 students without retardation, ages 8 through 13, indicated that (a) high percentages of both groups understood what loneliness means, (b) a loneliness questionnaire yielded satisfactory internal reliability with both groups, and (c) boys but not girls with mental retardation reported significantly more loneliness than did children without mental retardation. Suggestions were made for future research on loneliness in school settings. PMID- 1739453 TI - Differences in adolescents' self-concept as a function of academic level, ethnicity, and gender. AB - The relations of dimensions of self-concept of adolescents with their academic level, ethnicity, and gender were investigated. A self-concept inventory assessing 11 aspects of self-concept was administered to a sample of 1,140 eight grade students stratified with regard to academic level (regular class, educationally marginal, learning handicapped), ethnicity (white, black, and Hispanic), and gender. Results showed that regular class students had higher levels of self-concept on most scales than did students who were educationally marginal or learning handicapped; the latter two groups showed few differences. Black students had higher self-concept ratings than did white and Hispanic students on most scales. An interaction on two academically related dimensions of self-concept revealed that white students who were educationally marginal had the lowest level of academic and verbal self-concept. Implications of the results for theories of self-concept formation were discussed. PMID- 1739454 TI - Toward defining and measuring social skills in employment settings. AB - Although it is clear that appropriate social skills are related to job success, little agreement has been reached on how to define and measure social skills. In this article a definition of social skills was proposed that will begin to identify the components that need to be considered when teaching social skills to individuals with mental retardation in employment settings. In addition, three measurement approaches were discussed that further operationalize these components. Current social skills training research in employment settings was reviewed and discussed with respect to the measurement approaches proposed in this article. PMID- 1739455 TI - Social evaluation of behaviors comprising three social skills and a comparison of the performance of people with and without mental retardation. AB - We evaluated whether behaviors commonly taught to persons with mental retardation as part of three important social skills (following instructions, accepting criticism, and negotiating to resolve conflicts) were responded to favorably by other people. People with mental retardation who lived in the community and other people from the community participated in videotaped role plays involving each of the social skills. The performances of participants were scored according to behavioral checklists. Participants with mental retardation scored as well as other participants on following instructions and accepting criticism but lower on negotiating. Community members were asked to evaluate how well the participants did in the videotaped role-play situations. There were high positive correlations between the scores derived from the behavioral checklists and the evaluations of community members for both groups of participants. PMID- 1739456 TI - Social support networks of adults with mental retardation who live at home. AB - The social support networks of 418 adults with mental retardation who live at home were found to be large, durable, active, and diverse in their composition. Family members predominated as members of these support networks. Differences were found in many network characteristics based on the gender and level of mental retardation of the adults. Males and those with the most severe mental retardation were found to be at risk for social isolation. Contrasts with the social support networks of adults in nonfamily settings were discussed. PMID- 1739457 TI - Reconsidering the construct of mental retardation: implications of a model of social competence. AB - A historical overview of efforts to integrate social competence into a definition of mental retardation was provided. The existing AAMR definition was criticized for its incorporation of a muddled construct of adaptive behavior, which over emphasizes psychopathology and underemphasizes social intelligence. A model of general competence was presented, and mental retardation was reconceptualized as a condition characterized by deficits in social, practical, and conceptual intelligence. Although such a conceptualization would be an improvement on the current definition, we argued that a definition of mental retardation based on social competence outcomes (i.e., need for support in playing critical social roles) would be preferable to a definition that is still tied too closely to psychometric criteria. PMID- 1739458 TI - Signaling pathways in odorant detection. AB - The application of molecular genetic techniques has led to the identification of olfactory-specific proteins that represent each component in a second messenger cascade. Our current understanding of signaling in the olfactory system suggests that receptor proteins of a large family, responsible in part for the specificity of the system, converge on a relatively small number of second messenger systems. The ability to express these elements in heterologous systems should allow for the reconstitution of the signaling cascade and provide insight into the specificity of ligand binding, pathway activation, and signal termination. PMID- 1739459 TI - Neuronal precursor cells in the rat hippocampal formation contribute to more than one cytoarchitectonic area. AB - We have tested the hypothesis that cell lineage restriction boundaries define the borders between cytoarchitectonic areas in the cerebral cortex. Clonally related cells were identified using a retroviral marking technique, and the dispersion of neuronal clones was examined with respect to the transitions between cortical areas. We chose to study the hippocampal formation because we found that clones of hippocampal neurons, unlike those in neocortex, are compact and readily identifiable in the adult and that transitions between areas in the hippocampus are sharp relative to the spread of a typical clone. We conclude, contrary to the hypothesis, that clones of neurons transgress the boundaries between areas in the hippocampal formation, that border-crossing clones are observed as frequently as would be expected if clones spread freely over the hippocampus with no constraint imposed by area borders, and that different types of pyramidal neurons, characteristic of different areas, may appear to a single clone. different areas, may appear in a single clone. PMID- 1739460 TI - The role of interactions in determining cell fate of two identified motoneurons in the embryonic zebrafish. AB - The role of cellular interactions in determining the fates of two identified motoneurons in the embryonic zebrafish was investigated by transplanting individual motoneurons from labeled donor embryos to unlabeled hosts. The results suggest that although these cells normally adopt different fates, they form an equivalence group in which one fate is primary and the other is secondary. Both cells are able to adopt the primary fate. A cell that has adopted the secondary fate can be induced to switch to the primary fate by ablating the cell that has adopted the primary fate, even many hours after axogenesis. Although interactions between the two cells appear to regulate which cell adopts the secondary fate, these interactions seem to be independent of neuromuscular activity. PMID- 1739461 TI - Genes necessary for directed axonal elongation or fasciculation in C. elegans. AB - The outgrowth of single axons through different cellular environments requires distinct sets of genes in the nematode C. elegans. Three genes are required for the pioneering circumferential outgrowth of identified motor neuron axons between the lateral hypodermal cell membrane and the basal lamina. Three other genes are required for the longitudinal outgrowth of these axons along preexisting axon bundles as well as for the fasciculation of axons within these neuron bundles. Five additional genes are required for circumferential outgrowth, longitudinal outgrowth, and fasciculation; mutations in three of these genes disrupt axon ultrastructure, suggesting that they function in axon formation rather than in axon guidance. PMID- 1739462 TI - Molecular characterization of the Schwann cell myelin protein, SMP: structural similarities within the immunoglobulin superfamily. AB - The Schwann cell myelin protein (SMP), previously defined in quail and chick by a monoclonal antibody, is in vivo exclusively expressed by myelinating and nonmyelinating Schwann cells and oligodendrocytes. The isolation of the complete nucleotide sequence of SMP is reported here. The predicted polypeptide chain reveals that SMP is a transmembrane molecule of the immunoglobulin superfamily showing sequence similarities with several surface glycoproteins expressed in the nervous and immune systems. In spite of a 43.5% overall sequence identity between rat myelin-associated glycoprotein (MAG) and quail SMP, SMP does not seem to be the avian homolog of MAG, since their expression, regulation, and functions are significantly different. Unusual sequence arrangements shared by SMP, MAG, and two lymphoid antigens suggest the existence of a particular subgroup in the immunoglobulin superfamily. PMID- 1739463 TI - Interaction of free and synaptic vesicle-bound synapsin I with F-actin. AB - Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and F-actin in a phosphorylation-dependent fashion. We have found that dephosphorylated synapsin I induces a dose-dependent increase in the number of actin filaments, which at high ionic strength is abolished by synapsin I phosphorylation. The increase in filament number appears to be due to a nucleating effect of synapsin I and not to a barbed-end capping/severing activity. Synaptic vesicle-bound synapsin I was as effective as free synapsin I in increasing the number of filaments. These data support the view that synapsin I is involved in the regulation of the dynamics of the actin-based network during the exo-endocytotic cycle. PMID- 1739464 TI - The challenge of quality versus quantity in echocardiography. PMID- 1739465 TI - Diagnosis of aortic transection by transesophageal echocardiography. AB - Transesophageal echocardiography (TEE) offers spectacularly detailed images of thoracic aortic anatomy and blood flow; however, its utility for diagnosis of aortic trauma is unknown. Our case underscores the ability of TEE to diagnose aortic transection. The speed, mobility, and accuracy of TEE makes it an attractive means of diagnosing aortic trauma in the critically ill. PMID- 1739466 TI - Health Care Financing Administration release of final physician payment reform regulation. AB - The Health Care Financing Administration has released final regulations concerning physician payment reform. The new method will significantly affect global, technical, and professional reimbursement. The American Society of Echocardiography is preparing response to these regulations. PMID- 1739467 TI - Pseudocolor displays in B-mode imaging applied to echocardiography and vascular imaging: an update. AB - Cardiac and vascular ultrasound systems incorporting colorized gray-scale display options to supplement the standard B-mode gray-scale image have recently reappeared on the market from several manufacturers. As yet, the clinical benefit of this "new" technology is unknown, and recommendations and protocols for its best application are not available. This article reviews the limitations of the gray-scale displays currently used, the rationale of the color-supplemented B mode image, and some of the potential applications to cardiac and vascular ultrasound. PMID- 1739468 TI - A computer-aided approach for the quantitation of regional left ventricular function using two-dimensional echocardiography. AB - Quantitation of regional left ventricular function is becoming increasingly important in this era of interventional cardiology. In this article we describe a computer-assisted approach for the assessment of regional left ventricular function that integrates three features. First, it measures left ventricular wall thickening and endocardial motion and curvature during an entire systolic contraction sequence. Second, it allows us to easily define endocardial and epicardial borders without actually having to manually trace the entire border. Third, it displays complex data in a simple format for easy assimilation. We believe that this approach is practical and comprehensive and can be used to quantitate regional left ventricular function with two-dimensional echocardiography. PMID- 1739469 TI - Echocardiographic indexes of allograft rejection in pediatric cardiac transplant recipients. AB - To determine the usefulness of echocardiographic indexes of left ventricular (LV) function as possible predictors of cardiac rejection, 12 transplant recipients (ages 3 to 17 years) underwent a total of 52 serial echocardiographic examinations and cardiac biopsies. The results were compared to those of 12 normal children (ages 2 to 17 years). Biopsies were graded as no rejection (n = 23), mild rejection (cellular infiltrate, n = 13), and moderate rejection (myocyte necrosis, n = 16). LV dimensions, percent shortening fraction, indexed LV mass, and ejection fraction were measured from M-mode and two-dimensional echocardiography. From the mitral valve Doppler tracing, the following measurements were made: isovolumic relaxation time, peak E and peak A velocities, and the fraction of filling under the E and A waves as well as in the first third of diastole. Compared with normal subjects, transplant recipients with no rejection had higher heart rates (95 +/- 15 vs 80 +/- 17 beats/min), longer isovolumic relaxation time (68.8 +/- 11.2 vs 51.5 +/- 13.6 msec), decreased first third area fraction (0.48 +/- 0.10 vs 0.57 +/- 0.10), and similar shortening fraction, LV mass, and peak E and A velocities (p less than 0.03). Compared with transplant recipients with no rejection, patients in whom mild rejection developed also had decreased shortening fraction (31% +/- 10% vs 37% +/- 8%) and decreased peak E velocity (0.68 +/- 0.19 vs 0.88 +/- 0.15 m/s) (p less than 0.03). From mild to moderate rejection, no further changes were noted in any echocardiographic indexes measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739470 TI - Pulmonic valve endocarditis as an underdiagnosed disease: role of transesophageal echocardiography. AB - Pulmonic valve endocarditis is a rare clinical entity. In spite of an increase in the frequency of right-sided endocarditis, primarily it is the tricuspid valve that is involved. Two-dimensional transthoracic echocardiography has improved our ability to diagnose infective endocarditis but has not identified many cases of pulmonic valve endocarditis. With the use of transesophageal echocardiography, three recent cases of pulmonic valve endocarditis were diagnosed by our laboratory. Each of these patients had clinical evidence of right-sided endocarditis, yet routine transthoracic echocardiograms failed to identify any pulmonic valve abnormalities. The true incidence of pulmonic valve endocarditis may be higher than previously reported, and the transesophageal echocardiogram is the preferred method for identifying and evaluating pulmonic valve endocarditis in adults. PMID- 1739471 TI - Exclusion of atrial thrombus by transesophageal echocardiography. AB - To determine whether transesophageal echocardiography (TEE) is useful in ruling out the presence of atrial thrombus, we performed TEE in 20 patients immediately before valve replacement or valve repair and within 3 days of an autopsy in one patient. Mitral stenosis was the predominant lesion in three patients, mitral regurgitation was seen in 11 patients, five patients had mitral prosthesis malfunction, one patient had a tricuspid prosthesis malfunction, and one patient had aortic stenosis. Eight patients were in atrial fibrillation. Four patients demonstrated spontaneous contrast in the associated atria. Nine patients were receiving oral anticoagulation. Mean left atrial diameter was 5.3 +/- 1.3 mm. TEE revealed no evidence for atrial thrombus in 18 of the 21 patients; this finding was confirmed by careful inspection of the atria including the appendages. TEE demonstrated a left atrial thrombus in two patients and a right atrial thrombus in another (confirmed at the time of surgery or at autopsy). In all cases transthoracic echocardiography was negative. Our data suggest that TEE is useful in ruling out atrial thrombus, and therefore may be a useful test preceding interventions associated with an increased risk of embolism from the atria such as cardioversion, mitral valvuloplasty, or valve replacement. PMID- 1739472 TI - Comparison of transesophageal color flow Doppler imaging of normal mitral regurgitant jets in St. Jude Medical and Medtronic Hall cardiac prostheses. AB - Transesophageal color flow Doppler imaging of mitral mechanical prostheses is now widely used. This method eliminates the frequent problems of acoustic shadowing and flow masking that are commonly seen with a transthoracic Doppler study of mechanical mitral prostheses. Transesophageal color flow Doppler imaging was performed postoperatively in seven patients who had received St. Jude Medical mitral prostheses (St. Jude Medical, Inc., St. Jude, Minnesota) and in six patients who received Medtronic Hall mitral valves (Medtronic, Inc., Minneapolis, Minnesota). Maximal systolic regurgitant jet length and area determinations were obtained in all patients. A comparison of maximal jet lengths and areas for each type of mechanical prosthesis demonstrated that the Medtronic Hall prostheses produced longer maximal jet lengths (p = 0.0001) and larger jet areas (p = 0.0009) than those produced by the St. Jude Medical mitral valves. Medtronic Hall prostheses produce a large centrally directed jet, whereas St. Jude Medical prostheses typically generate three smaller jets. Recognition of these differences in transesophageal color flow Doppler images in these commonly used cardiac valve prostheses is necessary to avoid misinterpretation of the normally large systolic regurgitant jet of the Medtronic Hall prosthesis as representing prosthetic dysfunction. PMID- 1739473 TI - Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study. AB - The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults. PMID- 1739474 TI - Denver shunt causing abnormal right atrial mass: noninvasive determination of shunt patency by color-coded Doppler shuntography. AB - An unusual floating mass was detected in the right atrium of a 71-year-old man with liver cirrhosis and intractable ascites using two-dimensional echocardiography. The mass was caused by the venous tip of a Denver peritoneovenous shunt. Shunt patency could be assessed easily by compression of the pump body; this maneuver resulted in a laminar or turbulent flow that was recorded at the tip of the shunt in the right atrium by color-coded Doppler echocardiography. We are reporting the first case demonstrating the value of echocardiography in diagnosing a Denver shunt in the heart and shunt patency by color-coded Doppler shuntography. PMID- 1739475 TI - Right-to-left shunt through a patent foramen ovale caused by severe tricuspid regurgitation detected with color Doppler echocardiography. AB - We describe a 65-year-old patient with moderate combined mitral disease and severe tricuspid regurgitation, in whom the tricuspid regurgitant jet was oriented toward the interatrial septum. Color flow and pulsed Doppler demonstrated a late-systolic to mid-diastolic, right-to-left shunting of the tricuspid regurgitant jet through the foramen ovale. This finding was subsequently confirmed with transesophageal echocardiography. PMID- 1739476 TI - Two-dimensional and color Doppler echocardiographic diagnosis of penetrating missile wounds of the heart: chronic complications from intracardiac course of a bullet. AB - Two-dimensional echocardiography has gained a role in the management of the acute complications of penetrating cardiac trauma and in precisely localizing retained bullet fragments within the heart. We report the case of an 8-year-old boy with chronic symptoms after a bullet wound. In this case, traumatic mitral regurgitation caused by mitral leaflet perforation and retention of the bullet in the tricuspid annulus occurred because of an unusual intracardiac course of the projectile. The diagnosis was made by transthoracic echocardiography. The ability of two-dimensional echocardiography to delineate the true location of the foreign body within the heart and Doppler ultrasound to identify mitral valve perforation helped guide a prompt, efficient, and successful surgical procedure. PMID- 1739477 TI - Pulsed Doppler echocardiographic and color flow imaging detection of retrograde filling of anomalous left coronary artery from the pulmonary artery. AB - We report a case in which pulsed wave Doppler echocardiography and color flow imaging of blood flow direction in an anomalous coronary artery from the pulmonary artery assisted in the correct diagnosis and confirmed the adequacy of the surgical correction. Low-velocity color scales were used to show retrograde filling of the left coronary artery before surgery and antegrade filling of the left coronary artery after surgery. Detecting direction of blood flow in coronary arteries should increase the accuracy of the noninvasive diagnosis of anomalous left coronary artery from the pulmonary artery. PMID- 1739478 TI - Echocardiographic diagnosis of left ventricular outflow tract obstruction after mitral valvuloplasty with a flexible Duran ring. AB - We report on a patient in whom left ventricular outflow obstruction developed after mitral valve repair with a flexible Duran ring. This complication has been reported in 4.5% to 21% of patients when a rigid Carpentier ring was used but was thought to be eliminated with the use of flexible rings. PMID- 1739479 TI - Complementary role of two-dimensional and Doppler echocardiography in the diagnosis of left ventricular free-wall rupture. AB - We describe a case of left ventricular free-wall rupture of the heart in which the use of two-dimensional and Doppler echocardiography provided the diagnosis. The echocardiographic findings in this condition are discussed and a previously unreported finding is described. PMID- 1739480 TI - Identification of Chiari's network with transesophageal echocardiography. AB - A prominent Chiari's network may be difficult to distinguish from pathologic right atrial masses on transthoracic echocardiography. We report a 38-year-old woman who had a cerebrovascular accident. Transthoracic echocardiogram revealed an atrial septal aneurysm and a mobile right atrial mass. This mass was correctly identified as Chiari's network on the basis of the transesophageal echocardiographic findings of a broad base of attachment in the right atrium and filamentous nature of the mass. These findings were confirmed at surgery. PMID- 1739481 TI - Overseas dentists training scheme. PMID- 1739482 TI - Aspiration in dental local anaesthesia. AB - When injecting into a blood vessel (for example during intravenous sedation) it is essential to aspirate blood into the syringe prior to drug administration to ensure that the tip of the needle is lying within a vein. By the same token, when the injection is intended to be extravascular it would appear to be wise to ensure that no blood is aspirated into the syringe before drug delivery. This procedure is employed routinely by medical and nursing staff, but is not universally accepted by dentists prior to the administration of dental local anaesthetics. PMID- 1739483 TI - Recollected in tranquillity. A profile of Ernest Matthews. Interview by Colin Davis. AB - Emeritus Professor Ernest Matthews, living in happy retirement in a delightful, small nineteenth century house in Petersfield, looks about 70 years old, and is in fact 17 years older. He has made many contributions to the advancement of dentistry, and we asked him, as he looked back over the years, how he saw the dental world today compared with 60 years ago when he qualified. PMID- 1739485 TI - The education and training of personnel auxiliary to dentistry. PMID- 1739484 TI - Cause for concern. PMID- 1739486 TI - 'Orthodontic aspects of vocational training'. PMID- 1739487 TI - 'Orthodontic aspects of vocational training'. PMID- 1739488 TI - Meetings that matter. PMID- 1739489 TI - 'Equipment malfunction'. PMID- 1739490 TI - Recovery of transplanted tooth after root filling. PMID- 1739491 TI - 'A primary double molar tooth in a child with Russell-Silver syndrome'. PMID- 1739492 TI - 'After the contract ... which way now?'. PMID- 1739493 TI - 'Maxillofacial surgery should become a specialty of medicine'. PMID- 1739494 TI - 'Increased anterior crowding in the dentition'. PMID- 1739495 TI - 'Do you treat HIV positive patients?'. PMID- 1739496 TI - 'An urgent remedy needed'. PMID- 1739497 TI - 'Changes in the community periodontal index of treatment needs (CPITN) after periodontal treatment in a general dental practice'. PMID- 1739498 TI - 'Do you treat HIV positive patients?'. PMID- 1739499 TI - 'Is digit sucking of significance?'. PMID- 1739500 TI - Setting the record straight. PMID- 1739501 TI - A dental health education programme, including home visits, for nursery school children. AB - The aim of this study was to measure the effectiveness of three preventive programmes by measuring changes in oral hygiene, gingivitis and the uptake of dental care of nursery school and young primary school children living in areas of urban deprivation. The oral hygiene and gingivitis of a group of children who brushed their teeth daily at school improved during the study, but deteriorated during the summer holiday. A second group of children also brushed their teeth at school, and in addition their parents were given dental health education by a dental hygienist at home. Parents of a third group of children were given dental health education only at home. The oral hygiene and gingivitis of both the second and third groups improved and was maintained during the school holiday. The preventive programmes had little effect on the uptake of dental care in any of the study groups. PMID- 1739502 TI - The management of a plastic bullet injury to the mandible. AB - A patient hit by a plastic bullet sustained severe facial contusion and a comminuted fracture of the mandible with bone loss. There was a non-union of the fracture. The injury and the restoration of the defect are described and the use of plastic bullets is discussed. PMID- 1739503 TI - DNA fingerprinting of oral bacteria. AB - This elective study was conducted at the Dental School, University of Wales College of Medicine and at the University of Wales College of Cardiff School of Pure and Applied Biology. The student's interest in oral microbiology and desire to contribute to the work being performed in the field of oral microbiology, led him to concentrate his study on developing a DNA fingerprinting method to evaluate the putative new species of the genus Capnocytophaga. The genus Capnocytophaga, which contains Gram-negative, capnophilic fusiform-shaped bacteria, has been implicated in juvenile periodontitis and prepubertal gingivitis. However, the genus is also part of the normal oral flora. The student believed that there was an implication of the existence of both pathogenic and non-pathogenic strains of Capnocytophaga and developed a method of DNA fingerprinting to distinguish Capnocytophaga strains from clusters identified by Khwaja et al. The student felt that the study allowed insight into the tremendous potential of molecular techniques for furthering the understanding of dental disease and confirmed his ambition to pursue a career in academic oral microbiology. This area of study allows new associations to be made between specific bacteria and diseases, aiding the possibility of rapid and early diagnosis. PMID- 1739504 TI - Western Asia--a college visit. AB - The first newspaper for a fortnight is always read avidly by any homeward bound traveller. So it was for the passengers on Flight KL872 on Monday, November 4 after a Conference in Pakistan and India with the Royal College of Surgeons of England. It was not long before Guardian readers had found the article 'In the ruins of the Raj' by Mark Tully.* Uncannily, it recounted the splendour and majesty of the countries we had visited and yet, at the same time, expressed our fears for the future of these delightfully hospitable and intelligent people who had been our hosts in Pakistan and India for two weeks. PMID- 1739505 TI - Problems of the Pakistani dental education system. PMID- 1739506 TI - The clinical performance of a glass polyalkenoate (glass ionomer) cement used in a 'sandwich' technique with a composite resin to restore Class II cavities. AB - The use of glass polyalkenoate (GPA) cement in conjunction with composite resin using an acid etch technique is now well known and a 'sandwich' of tooth/GPA cement/composite resin has been recommended to form the cervical seal at the base of approximal boxes in Class II cavities. This paper reports on the 2-year results of a controlled clinical trial using a commercial GPA lining cement. The trial was designed to evaluate the efficacy of this 'sandwich' technique. Sixty four restorations in the mouths of 22 patients were evaluated during the 2.5 year period of the trial. The composite resin component of the restorations performed well. Five restorations failed, all in the region of the approximal box. Four failures were related to the exposed GPA cement component of the 'sandwich'. Failure was probably related to placement difficulties of the technique. The use of GPA cement laminated with composite resin when the GPA cement was enclosed within the final restoration appeared to be a successful technique. PMID- 1739507 TI - Permanent damage to inferior alveolar and lingual nerves during the removal of impacted mandibular third molars. Comparison of two methods of bone removal. AB - Injuries to the inferior alveolar or lingual nerve are recognised complications of third molar surgery. In a prospective study, permanent damage was found to be significantly related to bone removal using a surgical drill. The Howarth periosteal elevator may not provide adequate protection to the lingual nerve when a surgical drill is used. PMID- 1739508 TI - A practical gloving and handwashing regimen for dental practice. AB - The debate concerning the re-use of gloves in dental practice continues, despite the fact that recent guidelines on cross-infection control recommend that a new pair of gloves should be used for each patient. Whichever policy for glove use is adopted, it is important to take the maximum possible precautions in hand care. This paper presents a practical regimen for hand/glove washing which is simple, quick and effective. The importance of establishing a hand-care regimen in dental practice is emphasised. PMID- 1739509 TI - A unique natural tooth-supported partial denture. PMID- 1739510 TI - Tongue piercing: a new fad in body art. PMID- 1739511 TI - 'Computers in dentistry'. PMID- 1739512 TI - A severe case of amelogenesis imperfecta reported in a twin. PMID- 1739513 TI - Low-energy lasers in dentistry. PMID- 1739514 TI - Experience, skill and knowledge gained by newly qualified dentists during their first year of general practice. AB - This study was commissioned by the Department of Health in 1988 for the assessment of the preparation of newly qualified dentists for general practice and the effect of the Vocational Training Schemes on their development. Newly qualified dentists working either as VTS trainees or associates were assessed in three ways. During the third and the twelfth months of practice they were asked to keep a one-week clinical diary record. They were also asked to complete a questionnaire to give a subjective assessment of their skill and knowledge related to general practice. Similar questionnaires were completed by their trainers or principals in order to provide an objective assessment. An indication of the volume of treatment they provided was also obtained from DPB records. The results showed that associates saw more patients and provided more treatment than VTS trainees during their first year. The difference between the two groups was greater at 3 months than at 12 months; however, wide variations were found, especially in the VTS group. The results from the questionnaires suggest that, with the exception of practice administration, oral surgery, orthodontics, anaesthesia and sedation, the undergraduate course provides adequate preparation for the initial demands of general practice. However, initially both groups were judged to be unprepared for independent practice. The results suggest that during the first year of practice the support and guidance of a more experienced colleague is essential, together with the provision of adequate and varied clinical experience. PMID- 1739515 TI - Preventing moral distress: our ethical obligation. PMID- 1739516 TI - Quality of information and extent of the transformation within organizations. PMID- 1739517 TI - RBRVS: a primer for nurse executives. PMID- 1739518 TI - Torsade de pointes: chaos, sixteen years on? PMID- 1739519 TI - Provision of services for the diagnosis and treatment of heart disease. Fourth report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England. AB - The principal conclusions of the fourth report of the Joint Cardiology Committee are: 1 Cardiovascular disease remains a major cause of death and morbidity in the population and of utilisation of medical services. 2 Reduction in the risk of cardiovascular disease is feasible, and better co-ordination is required of strategies most likely to be effective. 3 Pre-hospital care of cardiac emergencies, in particular the provision of facilities for defibrillation, should continue to be developed. 4 There remains a large shortfall in provision of cardiological services with almost one in five district hospitals in England and Wales having no physician with the appropriate training. Few of the larger districts have two cardiologists to meet the recommendation for populations of over 250,000. One hundred and fifty extra consultant posts (in both district and regional centres) together with adequate supporting staff and facilities are urgently needed to provide modest cover for existing requirements. 5 The provision of coronary bypass grafting has expanded since 1985, but few regions have fulfilled the unambitious objectives stated in the Third Joint Cardiology Report. 6 The development of coronary angioplasty has been slow and haphazard. All regional centres should have at least two cardiologists trained in coronary angioplasty and there should be a designated budget. Surgical cover is still required for most procedures and is best provided on site. 7 Advances in the management of arrhythmias, including the use of specialised pacemakers, implantable defibrillators, and percutaneous or surgical ablation of parts of the cardiac conducting system have resulted in great benefit to patients. Planned development of the emerging sub-specialty of arrhythmology is required. 8 Strategies must be developed to limit the increased exposure of cardiologists to ionising radiation which will result from the expansion and increasing complexity of interventional procedures. 9 Supra-regional funding for infant cardiac surgery and transplantation has been successful and should be continued. 10 Despite advances in non-invasive diagnosis of congenital heart disease the amount of cardiac catheterisation of children has risen due to the increase in number of interventional procedures. Vacant consultant posts in paediatric cardiology and the need for an increase in the number of such posts cannot be filled from existing senior registrar posts. All paediatric cardiac units should have a senior registrar and in the meantime it may be necessary to make proleptic appointments to consultant posts with arrangements for the appointees to complete their training. 11 Provision of care for the increasing number of adolescent and adult survivors of complex congenital heart disease is urgently required. The management of these patients is specialised, and the committee recommends that it should ultimately be undertaken by either adult or pediatric cardiologists with appropriate additional training working in supra-regionally funded centers alongside specially trained surgeons. 12 Cardiac rehabilitation should be available to all patients in the United Kingdom. 13 New recommendations for training in cardiology are for a total of at least five years in the specialty after general professional training, plus a year as senior registrar in general medicine. An additional year may be required for those wishing to work in interventional cardiology and adequate provision must be made for those with an academic interest. 14 It is essential that both basic and clinical research is carried out in cardiac centres but these activities are becoming increasingly limited by the lack of properly funded posts in the basic sciences and restriction in the number of honorary posts for clinical research workers. 15 A joint audit committee of the Royal College of Physicians and the British Cardiac Society has been established to coordinate audit in the specialty. All district and regional cardiac centres should cooperate with the work of the committee, in addition to their participation in local audit activities. PMID- 1739520 TI - Vagaries of acceleration dependent aberration. PMID- 1739521 TI - Antiarrhythmic drug treatment: need for continuous vigilance. AB - Any physician treating cardiac arrhythmias should be aware of a possible worsening of the arrhythmia (so-called arrhythmogenesis) after the start of antiarrhythmic drug treatment. To facilitate the recognition of that complication the type and possible mechanisms of arrhythmogenesis are reviewed. Recognition also requires an understanding of (a) the time of appearance of arrhythmogenic effects after different drugs, (b) the value of non-invasive and invasive tests, and (c) the profile of the patient most likely to develop this problem. Guidelines are given to reduce the incidence of the arrhythmogenic effects of antiarrhythmic drugs and a plea is made that the physician should be always on the alert for this complication. PMID- 1739522 TI - Is there chaos in cardiology? PMID- 1739523 TI - Progress in familial hypertrophic cardiomyopathy: molecular genetic analyses in the original family studied by Teare. PMID- 1739524 TI - Electrical restitution in the endocardium of the intact human right ventricle. AB - OBJECTIVE: To characterise electrical restitution in the intact human heart. PATIENTS AND METHODS: A series of monophasic action potential electrical restitution curves were constructed from a single right ventricular endocardial site in eight patients (three men) without structural heart disease aged 52-68 (mean 55 years). A combination pacing/monophasic action potential electrode was used to pace and record monophasic action potentials at drive cycle lengths of from 350 ms to 1500 ms. Ventricular extrastimuli were delivered at 20 cycle intervals and decreased from the longest coupling interval attainable without escape beats. RESULTS: Restitution curves shifted downward and towards the left; steady state action potential duration shifted from the restitution plateau and descended the curve, the amount of shift being linearly related to drive cycle length in two patients in whom the relation could be assessed; the amount of monophasic action potential shortening was a function of the degree of prematurity and that relation was unaffected by drive rate; the magnitude of restitution and the time constant of the restitution curve were not changed significantly by altered drive cycle length. CONCLUSION: In the intact heart in vivo, electrical restitution (of the monophasic action potential) has similar characteristics to those (of the transmembrane action potential) in cellular preparations in vitro. Thus the alteration of action potential plateau currents by instantaneous rate change or drug effects, which can be directly observed by techniques available to the cellular electrophysiologist, may be indirectly assessed in vivo by characterisation of the effect of these on electrical restitution. PMID- 1739525 TI - Value of ambulatory ST segment monitoring in patients with chronic stable angina: does measurement of the "total ischaemic burden" assist with management? AB - OBJECTIVE: To assess the prognostic significance of transient ischaemic episodes during daily activities in patients with stable angina. PATIENTS AND METHODS: 172 patients with stable angina attending the cardiac outpatients departments of Hillingdon Hospital (n = 155) and the National Heart Hospital (n = 17) were prospectively studied by exercise testing and 48 hours of ambulatory ST segment monitoring, and followed for prognostic purposes for up to 39 months (mean 24.5 months). Patient inclusion depended on a clinical diagnosis of stable coronary artery disease which necessitated outpatient review (and antianginal treatment in 94% of patients). It was not dependent on objective evidence of reversible ischaemia. Events recorded during the follow up period included death, non-fatal myocardial infarction, unstable angina, and the requirement for revascularisation. RESULTS: 72 patients (42%) had transient ischaemic episodes during daily activities, and 104 patients (60.5%) had an ischaemic response to exercise. 63 patients (36%) had evidence of ischaemia on both investigations; with 59 (34%) having no documented ischaemia on either investigation. There were 27 patient events (15.7%) recorded over a mean 24.5 month follow up, including five deaths (2.9%) (three cardiac related (1.7%)), six non-fatal myocardial infarctions (3.5%), six admissions with unstable angina (3.5%), and 10 revascularisation procedures (5.8%). Of the nine "hard" or objective end points (cardiac death and non-fatal myocardial infarction), only two had evidence of transient ischaemia on ambulatory ST segment monitoring at initial investigation, with 10 of the 25 patients (38.5%) with any cardiac event having such episodes. CONCLUSIONS: The outcome in patients with chronic stable angina receiving standard medical treatment was good over a mean two year follow up period. For the purpose of assessing prognosis over this time scale, there was no advantage to performing ambulatory ST segment monitoring in such patients. PMID- 1739526 TI - Dr Dennis M Krikler: editor of the British Heart Journal 1981-91. PMID- 1739527 TI - Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic. AB - OBJECTIVE: To evaluate a clinic set up specifically to assess patients with recent onset chest pain, particularly those presenting with a normal resting electrocardiogram. DESIGN: Retrospective review of case notes. SETTING: Cardiac department of a tertiary referral cardiothoracic centre. PATIENTS: 250 consecutive patients with recent onset chest pain seen within 24 hours of general practitioner referral. OUTCOME MEASURES: Clinical diagnosis and management. RESULTS: 40% of patients were seen within seven days of the onset of symptoms. Twenty seven per cent had non-cardiac symptoms and could be discharged while 60% were considered to have cardiac pain. Sixty six patients (26%) were admitted directly from the clinic and 48 of these underwent coronary angiography within three weeks. Seventy patients (28%) have so far undergone intervention (angioplasty or coronary artery surgery), 22 within one month of presentation. One hundred and nine patients (44%) presented with a normal resting electrocardiogram, 21 of whom were considered to have unstable angina. Forty one of these patients were investigated of whom 37 were found to have significant coronary disease and 26 have undergone intervention. CONCLUSIONS: This experience highlights the inadequacy of a routine electrocardiogram reporting service in patients with recent onset of chest pain. An alternative facility offering immediate and complete cardiac assessment produced patient benefit with early diagnosis and intervention. Investigation of these patients, however, accounted for 5% of cardiac catheterisation laboratory throughput; this was a significant additional and unscheduled workload. PMID- 1739528 TI - "Subclinical" pacemaker syndrome: a randomised study of symptom free patients with ventricular demand (VVI) pacemakers upgraded to dual chamber devices. AB - OBJECTIVE: To determine whether symptom free patients with single chamber pacemakers benefit from dual chamber pacing. DESIGN: A randomised double blind crossover comparison of ventricular demand (VVI), dual chamber demand (DDI), and dual chamber universal (DDD) modes after upgrading from a VVI device. SETTING: Cardiology outpatient department. PATIENTS: Sixteen patients aged 41-84 years who were symptom free during VVI mode pacing for three or more years. INTERVENTION: Pacemaker upgrade during routine generator change. MAIN OUTCOME MEASURES: Change in subjective (general health perception, symptoms) and objective (clinical assessment, treadmill exercise, and radiological and echocardiographic indices) results between pacing modes before and after upgrading. RESULTS: 75% preferred DDD, 68% found VVI least acceptable with 12% expressing no preference. Perceived general well-being and exercise capacity (p less than 0.01) and treadmill times (p less than 0.05) were improved in DDD mode but VVI and DDI modes were similar. Clinical, echocardiographic, radiological, and electrophysiological indices confirmed the absence of overt pacemaker syndrome, although mitral and tricuspid regurgitation was greatest in VVI mode (p less than 0.01). CONCLUSIONS: Most patients who were satisfied with long term pacing in VVI mode benefited from upgrading to DDD mode pacing suggesting the existence of "subclinical" pacemaker syndrome in up to 75% of such patients. The DDI mode offered little subjective or objective benefit over VVI mode in this population and should be reserved for patients with paroxysmal atrial arrhythmias. VVI mode pacing should be used only for patients with very intermittent symptomatic bradycardia or atrial fibrillation with a good chronotropic response during exercise. PMID- 1739529 TI - Pacemaker electrode implantation in patients with persistent left superior vena cava. AB - Four out of 661 consecutive patients with permanent endocardial VVI pacing had the pacing lead introduced through a persistent left superior vena cava. It was difficult to introduce the lead from the right atrium into the right ventricle because the tip of the lead tended to be deflected away from the tricuspid orifice. This difficulty was overcome by shaping the lead into a pigtail with 3-4 cm wide loop. This avoided the risk of entering a branch of the coronary sinus in order to reach the right atrium. This technique made it easier to position the lead in the right ventricular apex. There were no complications in these four patients during a mean follow up of three years. PMID- 1739530 TI - Catheter ablation by low energy DC shocks for successful management of atrial flutter. AB - OBJECTIVE: To assess the effects of low energy ablation of the substrate for atrial flutter. DESIGN: Initial retrospective analysis of patients undergoing low energy ablation of the atrioventricular node for refractory atrial flutter (group 1) was followed by a prospective assessment of low energy ablation in the posterio-inferior right atrium for the same condition (group 2). SETTING: Tertiary referral centre for management of cardiac arrhythmias. PATIENTS: Seven men (aged 50-67 years) with refractory atrial flutter. INTERVENTIONS: Multiple (3 10) low energy DC shocks with a cumulative energy of 100-245 J in the region of the atrioventricular node in group 1 and 12-15 low energy DC shocks (cumulative energy 110-235 J) guided by the anatomical landmarks of the triangle of Koch and applied directly to the atrial wall. MAIN OUTCOME MEASURE: Freedom from recurrence of atrial flutter. RESULTS: In group 1 despite initial complete atrioventricular block in three patients, atrioventricular conduction had resumed in all by one month. All four, however, were in sinus rhythm at follow up six to 13 months later. Two of the three patients in group 2 were free of atrial flutter at follow up three to four months after ablation. CONCLUSION: Ablation of the atrial flutter substrate with low energy DC shocks is feasible. Precise electrophysiological mapping is not necessary. PMID- 1739531 TI - Early and late arrhythmias after the Fontan operation: predisposing factors and clinical consequences. AB - OBJECTIVE: To study the incidence, predisposing factors, and clinical significance of arrhythmias early and late after the Fontan operation for congenital heart disease. PATIENTS AND METHODS: All 104 consecutive patients undergoing Fontan repair from 1975 to 1988 were studied retrospectively. Hospital records were reviewed for perioperative arrhythmia. Clinical information and annual electrocardiograms were available for all 78 hospital survivors during a follow up of up to 13 years (mean 3.7 years). Ambulatory electrocardiographic monitoring was performed in 67 patients (81%). RESULTS: Eleven patients (10.6%) developed a perioperative tachycardia (eight, atrial flutter; three, His bundle tachycardia). Multivariate analysis showed that raised preoperative mean pulmonary artery pressure and low aortic saturation were significant risk factors for the development of atrial flutter (r2 = 0.32, p = 0.0001) but not for His bundle tachycardia. Despite intensive medical treatment 10 of these 11 patients died. At the last visit 72 (92%) of the 78 patients were in sinus rhythm on their standard 12 lead electrocardiogram. Junctional rhythm was present in three patients, two patients had atrial flutter, and one had a paced rhythm. Ambulatory monitoring did not show important bradycardia or ventricular arrhythmias. Actuarial survival free of supraventricular arrhythmia was 82% at eight years after operation. Multivariate analysis identified older age, increased right atrial size, and raised mean preoperative pulmonary artery pressure as risk factors for arrhythmia during intermediate follow-up (r2 = 0.46, p less than 0.001). Late tachycardias, in contrast to those occurring in the perioperative period, were not associated with an increased mortality. CONCLUSIONS: Except for his bundle tachycardia in the perioperative period, early and late arrhythmias after a Fontan operation seem to be a consequence of adverse preoperative and postoperative haemodynamic function. The perioperative outcome is therefore poor even when the patient can be restored to sinus rhythm. Medical and surgical modifications to improve the haemodynamic disturbances associated with arrhythmias are therefore indicated. PMID- 1739532 TI - Atrial flutter in the fetus and young infant: an association with accessory connections. AB - OBJECTIVE: To highlight the association between atrial flutter and accessory connections in the fetus and young infant. DESIGN: A retrospective review from January 1985 to January 1990. PATIENTS: Fetuses, neonates, and young infants with atrial flutter. RESULTS: Four fetuses and five infants presented with atrial flutter. In two fetuses and one infant sinus rhythm returned spontaneously. The other six required cardioversion. Three of them developed orthodromic atrioventricular re-entry tachycardia and each had evidence of an accessory connection. CONCLUSIONS: Because atrial flutter in the fetus and neonate is rare, the high incidence of accessory connections in this group points to a possible aetiology of "idiopathic" atrial flutter in this age group. PMID- 1739533 TI - Normal relation between heart rate and cardiac repolarisation in sudden infant death syndrome. AB - OBJECTIVE: To determine whether there was a difference in the relation between heart rate and RT intervals in infants who later died of sudden infant death syndrome (SIDS) and controls. DESIGN: A blinded, computer analysis of prospectively acquired physiological data on SIDS cases and controls. SETTING: Physiological data obtained from infants at home (collaborative analysis National Heart and Lung Institute and Exeter University). PARTICIPANTS: Nine fullterm infants who subsequently died of SIDS and 10 surviving controls matched for age and birth weight. INTERVENTIONS: 24 hour tape recordings of the electrocardiogram at home between three and 11 weeks of age. MAIN OUTCOME MEASURES: Mean value of the constant b, which relates by linear regression the log of each RT interval to the log of its proceeding RR interval, and any difference between SIDS cases and controls. RESULTS: The mean (2SEM) values for b were 0.20 (0.03) for the 10 controls and 0.19 (0.03) for the nine SIDS infants. Cyclical correlations between RT and RR intervals of varying strength were identified in both SIDS infants and controls. CONCLUSIONS: Infants who subsequently died of SIDS did not show an impaired ability to modify RT intervals in response to change in heart rate. PMID- 1739534 TI - Myocardial dysfunction in treated adult hypopituitarism: a possible explanation for increased cardiovascular mortality. AB - OBJECTIVE: To assess cardiac structure and function in patients with treated hypopituitarism and to determine their relation to the degree of growth hormone deficiency and body composition pattern. DESIGN: 26 patients with treated hypopituitarism were studied by cross sectional and Doppler echocardiography and by exercise testing. The results were analysed and their relation to the degree of growth hormone deficiency and body composition determined. SETTING: All tests were performed in the department of cardiology and the unit of metabolic medicine at a tertiary referral centre. PATIENTS: Patients with hypopituitarism referred for endocrine assessment. MAIN OUTCOME MEASURES: Left ventricular mass, left ventricular diastolic function, and exercise capacity in patients with hypopituitarism and their relation to growth hormone deficiency. RESULTS: Mean (SD) serum concentration of insulin-like growth factor 1 (IGE-1), a measure of growth hormone deficiency, was 82.4 (45) micrograms/l. Lean body mass calculated by measuring total body potassium was 50 (9) kg. All patients had a normal left ventricular mass index and a normal left ventricular ejection fraction. Eight patients had abnormal left ventricular diastolic function. There was a significant correlation between IGF-1 and left ventricular mass (r = 0.45, p less than 0.02). Lean body mass was also significantly correlated with left ventricular mass (r = 0.78, p less than 0.0001) and left ventricular diastolic function (r = -0.63, p less than 0.01). The mean exercise duration was 8.6 (3.6) minutes. There was a significant correlation between serum IGF-1 and the rate pressure product on exercise (r = 0.47, p less than 0.01). Seven patients had planar ST segment depression greater than 0.1 mV during exercise testing. In five of these patients there was rapid resolution of ST segment depression immediately after exercise. Two patients developed considerable ST segment depression, and subsequent coronary angiography showed normal coronary arteries. Exercise-induced ST segment depression was not related to the severity or duration of growth hormone deficiency or serum cholesterol concentration. CONCLUSIONS: This study suggests that left ventricular mass and the rate-pressure product are related to the degree of growth hormone deficiency, that left ventricular diastolic dysfunction is frequently seen in hypopituitarism, and that these patients may have ischaemic-like ST segment changes during exercise testing. These findings may explain the increased cardiovascular mortality in patients with hypopituitarism and may also have implications for growth hormone replacement therapy in adults. PMID- 1739535 TI - Recurrent ventricular arrhythmias complicating myocardial infarction in the presence of phaeochromocytoma. AB - After an acute myocardial infarction a 49 year old man developed late recurrent severe ventricular arrhythmias coincident with transient hypertensive episodes. A phaeochromocytoma was diagnosed on the basis of the urinary concentration of catecholamines and computerised tomography of the adrenal glands. After stabilisation of his cardiac rhythm and blood pressure with alpha and beta adrenergic blockade and anti-arrhythmic treatment the right adrenal gland, which contained the tumour, was successfully resected. The diagnosis of a phaeochromocytoma should be considered when recurrent ventricular arrhythmias are associated with intermittent hypertension after myocardial infarction. PMID- 1739536 TI - Impact of catheter and surgical ablation on arrhythmia treatment in a tertiary referral centre. AB - Invasive cardiac electrophysiology studies began as diagnostic studies. The past decade has seen the introduction of several new treatments which have broadened the scope of invasive electrophysiology studies. In particular, the development of catheter ablation techniques increasingly allows curative treatment to be delivered in the catheter laboratory. The workload of electrophysiological procedures has steadily increased in our tertiary referral centre. Over 1000 patients have been treated in the past 20 years and it is projected that 219 new patients will be treated in 1991 and 342 procedures will be carried out. Over 25% of patients now receive either catheter or surgical ablation and almost 80% of these are cured permanently without the need for further drug treatment. The development of safer techniques for catheter ablation has led to its increased use and a decline in surgical ablations. Because catheter ablation is a much simpler and less traumatic procedure than surgical ablation there are great advantages both for the patient and in terms of cost-effectiveness. Antitachycardia pacing, relatively common in 1985, has now largely been supplanted by ablation and implantation of defibrillators. As the tendency to non pharmacological treatment increases and evidence mounts that cost-effectiveness is greater for electrophysiological treatments, the implications for the funding of electrophysiology services grow. The initially high cost of curative treatment needs to be balanced against the longer term and potentially higher costs of palliative drug treatment. The potential to cure patients with catheter procedures may lead to a greater demand for this expertise and a need for an increase in training and facilities. PMID- 1739537 TI - A proactive resolution. PMID- 1739538 TI - Nursing assessment of the elderly for dermatologic procedures. AB - The fastest growing group of Americans are senior citizens. The elderly patient is more at risk due to age, general health, chronic disease, and drugs. A good nursing assessment will help the nurse identify health problems that may affect the surgical outcome. PMID- 1739539 TI - The role of the histotechnician in Mohs surgery. AB - Critical elements of Mohs micrographic surgery are performed by the histotechnician in the frozen section laboratory. This article provides an overview of the essential role of the histotechnician as a member of the micrographic surgical team. PMID- 1739540 TI - Assessment of the photosensitive patient. AB - Photosensitivity is an abnormal cutaneous response to photosensitizing substances and sunlight or artificial light. Proper assessment of the photosensitive patient is important in defining photosensitive diseases and reactions. PMID- 1739541 TI - Redefining identity when appearance is altered. AB - Alteration in appearance, impacting on identity, can occur when cancer or other chronic illness strikes. Patients and families need assistance in coping with changes and redefining a sense of self during treatment and beyond. This article examines some common effects of therapy and disease on appearance and outlines a nursing plan of care to assist the patient in regaining acceptance in the outer world. PMID- 1739542 TI - [Technology, the client, the nurse and her resources]. PMID- 1739543 TI - Retirement to renal failure: the management of the elderly dialysis patient. PMID- 1739544 TI - Patient assessment in acute hemodialysis. PMID- 1739545 TI - Early tracheal intubation with thiopentone in elective surgery. AB - We have studied tracheal intubating conditions within 30 s of administration of thiopentone in 24 patients and compared this with our usual method of tracheal intubation, which involves 3 min of manual ventilation in 29 patients. All patients received papaveretum 10 mg 3 min before induction and alcuronium at induction of anaesthesia. Satisfactory intubating conditions were observed in 83% of patients in both groups. There were no difficult or failed intubations and no patient had laryngospasm. The duration of laryngoscopy in the control group was 14.1 (SD 8.6) s (range 7-50 s), compared with 12.4 (3.1) s (range 6-20 s), in the early intubation group (ns). In the control group there was a significant decrease in systolic pressure before tracheal intubation and a significant increase in heart rate after intubation, compared with baseline values. The average systolic pressure in the early intubation group increased only minimally: from a pre-intubation value of 143.3 (21.2) mm Hg to 145.5 (25.1) mm Hg after intubation. Our results demonstrate that early tracheal intubation under thiopentone supplemented with an opioid and a non-depolarizing neuromuscular block is feasible, associated with minimal changes in arterial pressure and not accompanied by an increased incidence of side effects. PMID- 1739546 TI - Delayed presentation of an extradural abscess complicating thoracic extradural analgesia. AB - Extradural abscess is a rare but recognized complication of extradural anaesthesia. Previous reports have been associated with a short time interval between extradural catheterization and presentation. We report a patient with rheumatoid arthritis, receiving steroid therapy, in whom an extradural abscess did not present until 23 days after the insertion of a thoracic extradural catheter to provide postoperative analgesia. PMID- 1739547 TI - Clonidine in the treatment of alcohol withdrawal in the intensive care unit. AB - We present two cases of patients with a past history of alcohol abuse admitted to the Intensive Care Unit (ICU) for treatment of respiratory problems, after multiple trauma and after sub-total colectomy, respectively. In both patients, features of alcohol withdrawal were prominent after sedation had been discontinued. Both were treated successfully with an infusion of clonidine. PMID- 1739548 TI - Retrograde intubation using the subcricoid region. AB - The applied anatomy of the cricothyroid and cricotracheal region of the neck and a retrograde method of tracheal intubation using the subcricoid region are described. This approach has several advantages, including absence of bleeding complications, as there are no major blood vessels on the cricotracheal membrane, and reduction in the possible development of subglottic oedema and stenosis. PMID- 1739549 TI - Management of carboxyhaemoglobinaemia. PMID- 1739550 TI - Management of carboxyhaemoglobinaemia. PMID- 1739551 TI - Analysis of effects of drug combinations. PMID- 1739552 TI - Iatrogenic foreign body after laryngoscopy. PMID- 1739553 TI - Gastric emptying in pregnancy. PMID- 1739554 TI - Propofol sedation for outpatient upper gastrointestinal endoscopy. PMID- 1739555 TI - Extradural haematoma after continuous extradural anaesthesia. PMID- 1739556 TI - Difficult laryngoscopy. PMID- 1739557 TI - Extradurals and balanced analgesia. PMID- 1739558 TI - Failed tracheal intubation at caesarean section and the laryngeal mask. PMID- 1739559 TI - Reported significant observations during anaesthesia: a prospective analysis over an 18-month period. AB - We describe a prospective analysis, in one hospital, of reported significant observations involving unsafe practices and working conditions during anaesthesia. Of the 549 significant observations reported voluntarily during a period of 18 months, 82% involved occurrences which were considered preventable and 27% could have been fatal if they had not been recognized and corrected. Ninety-three percent of incidents did not lead to a negative outcome. Human error was responsible for 411 (75%) reports. Lack of vigilance and failure to check were the most frequently reported factors associated with human error. Significant observations involving errors in drugs administration were the most frequent. Forty-five percent of all reported significant observations were made during maintenance of anaesthesia. PMID- 1739560 TI - Effect of oxygen therapy on late postoperative episodic and constant hypoxaemia. AB - As constant hypoxaemia itself may trigger development of apnoea and periodic breathing, we have studied the effect of oxygen therapy on the occurrence of late postoperative episodic hypoxaemia. Thirty-five patients without cardiopulmonary disease and undergoing elective total hip replacement were monitored with a pulse oximeter on the second night after operation (23:00 to 07:00), receiving either 21% or 37% oxygen by face mask in a randomized double-blind design. Mean oxygen saturation was greater in the group receiving 37% oxygen than in those having 21% oxygen (96% vs 92%, P less than 0.01). There was a weak correlation between mean oxygen saturation and the total number of hypoxaemic episodes (rs = -0.62, P less than 0.001), explained partly by the calculated (non-mechanistic) reduction in mean saturation by the episodes of hypoxaemia. There was no significant difference between the groups in the total number of sudden decreases in oxygen saturation, the duration of the events or number of patients with events to more or less than 80% oxygen saturation, although there was a trend towards fewer patients having events to less than 80% in the 37% oxygen group (nine of 17 patients vs five of 18 patients (ns); 95% confidence limits of median difference: -6 to 56%). We conclude that postoperative oxygen therapy with 37% oxygen by face mask increases mean oxygen saturation, but does not influence the basic mechanism leading to episodic hypoxaemia. PMID- 1739561 TI - Postoperative hypoxaemia after major abdominal vascular surgery. AB - We have studied the severity and duration of nocturnal hypoxaemia before operation and for the first five nights after operation after elective major abdominal vascular surgery. Oxygen supplementation was almost 100% effective in keeping oxygen saturation greater than 90% during the early postoperative period; however, 50% of patients spent prolonged periods with an SpO2 less than 85% during at least one night after operation. The risk of severe hypoxaemia persists well beyond the current prescription of supplementary oxygen in these high risk patients. A significant association exists between the mean preoperative overnight saturation value and the nocturnal saturation observed subsequently in the later postoperative period. PMID- 1739562 TI - Effects of i.v. midazolam on upper airway resistance. AB - We have measured changes in supraglottic airway resistance (Rsg) produced by midazolam. Ten subjects were studied on two occasions, receiving in a random order either midazolam 0.1 mg kg-1 or placebo. Supraglottic pressures were measured using a balloon-tipped catheter and air flow with a pneumotachograph. Rsg were calculated at a flow rate of 0.3 litre s-1 during inspiration. No changes in Rsg and no apnoeic events were noted following placebo injection. Mean Rsg increased from 0.23 (SEM 0.07) kPa litre-1 s to 1.29 (0.38) kPa litre-1 s 5 min after injection of midazolam (P less than 0.01), and remained increased significantly for 20 min. Twenty-two apnoeic events were recorded in six subjects, including 11 obstructive events. We conclude that midazolam in sedative doses increases Rsg markedly and induces central apnoea during the first few minutes after i.v. administration and this is followed by obstructive apnoea. PMID- 1739563 TI - Paediatric day-case surgery. PMID- 1739564 TI - Effects of posture, phonation and observer on Mallampati classification. AB - We have studied the effects of phonation and posture on the Mallampati classification of view of the pharyngeal structures. Differences between observers were allowed for by the experimental design and log-linear modelling. Sixty-four patients were assessed on the ward, sitting upright, with and without phonation, by each of two observers. Another 64 patients were assessed without phonation, but both upright and supine, again by both observers. Phonation (the patient saying "Ah") produced a marked, systematic improvement of view; moving to the supine posture produced a small, systematic, non-significant worsening of the view. Differences between observers were non-systematic but substantial. About 25% of patients phonated spontaneously. It is recommended that anaesthetists make their own assessments of Mallampati classification, with the patient in either of the postures but always either with or without phonation, and thereby gradually "calibrate" their assessments against the degree of difficulty encountered in intubation. PMID- 1739565 TI - A high flow semi-open system for preoxygenation: an evaluation. AB - We have compared an alternative breathing system for preoxygenation comprising a Hudson face mask with high oxygen inflow (48 litre min-1) and a Mapleson A breathing system (100 ml kg-1 min-1). The study consisted of two parts: the first involved adult volunteers (10 male, seven female) and the second part used a lung model for spontaneous ventilation with a sinusoidal ventilatory wave pattern. In the volunteers, preoxygenation was achieved at mean times of 138 (SD 31.3) s and 164 (SD 36.7) s with the high flow semi-open and Mapleson A systems, respectively. In the lung model, at peak inspiratory flow rates of 30 and 40 litre min-1, the preoxygenation times were 139 and 120 s, respectively, with the semi-open system and 167 and 156 s with the Mapleson A system. The high flow semi open system may be an alternative for current techniques, provided peak inspiratory flows are not excessive. PMID- 1739566 TI - Fresh gas requirements of an enclosed afferent reservoir breathing system during controlled ventilation in children. AB - An enclosed afferent reservoir breathing system (EAR) designed by Ohmeda was evaluated during anaesthesia with controlled ventilation in 104 healthy children. Carbon dioxide production and arterial carbon dioxide tension were measured in 12 children in order to determine the proportion of fresh gas (VF) involved in gas exchange. When the ratio of minute volume ventilation to fresh gas flow (VE:VF) exceeded 1.5, fractional utilization of fresh gas with the EAR was 0.92. This value and values of carbon dioxide production obtained from 43 children were used to derive a simple formula relating fresh gas flow requirements to body weight. The formula, VF = 0.6 x weight 0.5, was assessed in 49 children weighing 10-70 kg. The mean end-tidal partial pressure of carbon dioxide in these patients was 4.5 kPa (range 3.8-5.2 kPa). We conclude that the EAR has an efficiency of 92% in the use of fresh gas during controlled ventilation in healthy children, provided the VE:VF ratio is greater than 1.5. Under these conditions, normocapnia to mild hypocapnia was produced accurately using the formula VF = 0.6 x weight 0.5. PMID- 1739567 TI - Sighs and their effect on the breathing of patients anaesthetized with infusions of propofol. AB - Twenty-one spontaneous sighs were analysed from records of the breathing of 10 patients anaesthetized for 22-42 (mean 28.7) min with propofol infusions. Sighs occurred in eight patients, the rate varying between once in 29 min and four times in 26 min. There was no pattern in breaths preceding sighs, but the succeeding breaths were altered. On the first succeeding breath, tidal volume was reduced by a mean of 32% (95% confidence limits 19-44%; P less than 0.01) and inspiratory time by a mean of 15% (95% confidence limits 8-22%; P less than 0.01) of the means of the preceding breaths. These effects lasted on average at least 10 breaths. Expiratory time was usually slightly prolonged after a sigh, but this effect was less clear, less consistent and less prolonged. Sighs in patients anaesthetized with propofol reduce the ventilatory drive (in terms of mean inspiratory flow), and alter the timing, of succeeding breaths. PMID- 1739568 TI - Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective caesarean section. AB - Serial haemodynamic investigations were performed in 32 women who were allocated randomly to receive either spinal or extradural anaesthesia for elective Caesarean section. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. Doppler flow velocity waveforms were recorded also from the umbilical artery. Preloading with Ringer lactate solution 1 litre increased cardiac output in both groups. After injection of bupivacaine, cardiac output remained increased in the extradural group, but decreased in the spinal group. This was associated with an increase in umbilical artery pulsatility index in the spinal group. Umbilical artery pH was less in the spinal group (7.22 vs 7.27), although no neonate was depressed at birth. The maximum percentage change in cardiac output and umbilical artery pulsatility index correlated with umbilical artery pH (r = 0.54, r = 0.72, respectively). There was no significant correlation with change in arterial pressure. PMID- 1739569 TI - First-time coronary artery bypass grafting: the anaesthetist as a risk factor. AB - We have investigated the contribution of the anaesthetist and surgeon to outcome after 1301 consecutive coronary artery bypass grafting operations (first operation). The mean + 1 SD aspartate amino transferase concentration on the day after surgery (AST-D1) was 134 u litre-1 (or, after logarithmic transformation, 94 u litre-1). Twenty patients were selected at random from each of three groups having AST-D1 less than 100 u litre-1, 100-134 u litre-1 or greater than 134 u litre-1; positive ECG diagnoses of perioperative myocardial infarction were significantly more frequent with AST-D1 values greater than 100 u litre-1 than with smaller values, but no more frequent with AST-D1 greater than 134 u litre-1. Because several deaths occurred before AST-D1 could be measured, an "adverse outcome" was defined as either hospital death or AST-D1 greater than 100 u litre 1. Univariate analysis implicated both anaesthetist and surgeon as significant predictors of adverse outcome but, after allowing for 12 patient-related factors, only cardiopulmonary bypass time (or ischaemic cross-clamp time) (P less than 0.01) and anaesthetist (P = 0.05) were associated significantly with outcome. PMID- 1739570 TI - Induction dose-response of propofol in unpremedicated children. AB - The induction dose requirements of propofol were compared in three age groups in 300 unpremedicated healthy Chinese children: group A, younger than 2 yr (n = 48); group B, 2-5 yr (n = 117); group C, 6-12 yr (n = 135). Patients in each group were allocated randomly to receive one of eight doses of propofol (1.2, 1.4, 1.6, 1.8, 2.0, 2.2, 2.4 and 2.6 mg kg-1). ED50 and ED95 for loss of eyelash reflex (LER) and acceptance of face mask (AFM) were determined using probit analysis. ED50 and ED95 for both LER and AFM were greatest in group A, less in B and smallest in C; ED95 (AFM) for groups A, B and C were 2.88 (2.55-3.36), 2.53 (2.31 2.86), and 2.20 (2.02-2.46) mg kg-1, respectively. This probably represented their effective induction dose. The incidence of apnoea was dose related, but not pain on injection. PMID- 1739571 TI - Effect of addition of hyaluronidase to bupivacaine during axillary brachial plexus block. AB - We have studied in 22 patients the effect of adding hyaluronidase to bupivacaine during axillary brachial plexus block (BPB) in a double-blind design. Patients received BPB using bupivacaine 2 mg kg-1 with adrenaline 1 in 200,000, either with or without hyaluronidase 3000 iu, in a volume of 0.5 ml per 2.54 cm of the patient's height. The use of hyaluronidase did not increase the speed of onset of anaesthesia or reduce the incidence of inadequate nerve block. Hyaluronidase produced a significant reduction in the duration of anaesthesia. Changes in grip strength and skin temperature were useful in assessing the onset and progress of BPB. PMID- 1739572 TI - In vitro contracture tests in patients with various neuromuscular diseases. AB - In order to investigate the relationship between neuromuscular disease and malignant hyperthermia (MH) susceptibility, the caffeine and halothane in vitro contracture test (European Malignant Hyperthermia Group Protocol) were performed in 60 patients who underwent muscle biopsy for investigation of a clinically suspected neuromuscular disorder. Two test results were classified as MH susceptible, 10 as MH equivocal and 48 MH negative. The large number of equivocal results is thought to indicate the lack of specificity of the individual components of this test in patients with clinical or histological evidence of neuromuscular disease. The increased in vitro sensitivity to the drugs tested may nevertheless provide some explanation for several in vivo "MH-like reactions" reported frequently in these patients. These reactions, however, are likely to be based on pathophysiological mechanisms different from those responsible for a true MH crisis. PMID- 1739573 TI - Treatment of postoperative pain with diclofenac in uvulopalatopharyngoplasty. AB - Diclofenac sodium suppositories 150-200 mg day-1 were compared with placebo in a double-blind study during the first 3 days after uvulopalatopharyngoplasty in 40 patients with habitual snoring or obstructive sleep apnoea syndrome. Consumption of rescue analgesics (paracetamol suppositories) and pain assessed by a visual analogue scale were significantly less in the diclofenac group. Bleeding time (modified Ivy's test) and reported side effects did not differ between the two groups. PMID- 1739574 TI - MAC-awake of isoflurane, enflurane and halothane evaluated by slow and fast alveolar washout. AB - End-tidal anaesthetic concentrations at first eye opening in response to a verbal command during recovery from anaesthesia (MAC-awake), were measured for isoflurane (n = 16), enflurane (n = 16) and halothane (n = 14). MAC-awake was measured during either slow or fast alveolar washout. Slow washout was obtained by decreasing anaesthetic concentrations in predetermined steps of 15 min, assuming equilibration between brain and alveolar partial pressures. Fast alveolar washout was obtained by discontinuation of the inhalation anaesthetic, which had been maintained at 1 MAC for at least 15 min. Mean MAC-awake obtained with slow alveolar washout was similar for isoflurane (0.25 (SD 0.03) MAC), and enflurane (0.27 (0.04) MAC) and significantly greater than values obtained by fast alveolar washout (isoflurane: 0.19 (0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isoflurane and enflurane was significantly less than that of halothane, which was 0.59 (0.10) MAC as evaluated by the slow and 0.50 (0.05) MAC as evaluated by the fast alveolar washout method. Recovery time from anaesthesia with fast alveolar washout was 8.8 (4.0) min for halothane, which was not different from isoflurane (15 (2.5) min), but significantly shorter than for enflurane (22 (10) min), reflecting differences in the anaesthetic concentration gradient between MAC and MAC-awake values. These data do not support the hypothesis of a uniform ratio between MAC and MAC-awake values. PMID- 1739575 TI - Recognition and management of difficult airway problems. PMID- 1739576 TI - Sedation after cardiac bypass surgery: comparison of propofol and midazolam in the presence of a computerized closed loop arterial pressure controller. AB - Forty patients who had undergone coronary artery graft surgery and who required vasodilator therapy for postoperative hypertension were given infusions of either propofol (2,6,di-isopropylphenol) or midazolam, together with an infusion of morphine for analgesia while ventilation was controlled artificially. Sodium nitroprusside was administered to patients in both groups using a computer controlled closed loop system. Both agents produced good quality of sedation. Overall times to spontaneous ventilation and tracheal extubation were shorter in the propofol group, but this was not statistically significant. Ease of control of arterial pressure was satisfactory clinically with both agents, although propofol appeared to be associated with a statistically greater incidence of hypotension. PMID- 1739577 TI - The specific dermatoses of pregnancy: the British perspective. PMID- 1739578 TI - Acoustic microscopy: can you hear the diagnosis? PMID- 1739579 TI - Advances in vulvar disease: lichen sclerosus et atrophicus et al. PMID- 1739580 TI - Prenatal diagnosis of severe dermatologic diseases. AB - It is obvious that the nature of prenatal diagnosis of severe or lethal skin conditions is rapidly evolving. New molecular, enzymatic, and ultrastructural markers will become available. The biochemical base of many of these disorders will become known and the accuracy and utility of in utero diagnosis will improve. We wish to make one point again. The field is rapidly outpacing the ability of review articles to keep current. We urge you to refer to a genetic center for information when you are dealing with a situation in which prenatal diagnosis may be an issue. PMID- 1739581 TI - Advances in alopecia areata and androgenetic alopecia. PMID- 1739582 TI - Topical product design and extemporaneous compounding in dermatology. PMID- 1739583 TI - Phototherapy and photochemotherapy. PMID- 1739584 TI - Update on chemical peels. AB - The area of chemical peeling has seen an explosion of growth and interest in the last 5 years. The use of peeling for the therapy of pigmentary dyschromias, actinic keratoses and rhytides, depressed scarring, and in selected cases, irradiation dermatitis, is amplified by the discovery of new wounding agents and new variations in technique. Appropriate growth in the objective evaluation of these agents and techniques is dependent on the demonstrative histology and the sharing of knowledge of both excellent results and significant complications in the dermatologic surgical literature. PMID- 1739585 TI - Superficial anatomy and cutaneous surgery of the hand. PMID- 1739586 TI - Keratinocyte cytokines. AB - It is now clear that keratinocytes produce a wide range of cytokines that can be regarded as important mediators of intercellular communication. A major emphasis has been placed on IL-1 because of its relationships with other cytokines and other differentiated tissues. Dysregulation of IL-1, IL-1 receptor, and inhibitory factors for IL-1 may cause imbalance of skin biology, leading to perpetuation of immune and inflammatory events. Interaction of IL-1 with other cytokines in vivo is also important in the understanding of the pathophysiology of skin diseases. More fundamental questions regarding the homeostatic significance of IL-1 in keratinocytes still remain to be answered. PMID- 1739587 TI - Imaging of the temporal bone. AB - High-resolution CT remains the imaging modality of choice for investigation of the temporal bone, especially if there is suspicion of bony involvement. The advances in two- and three-dimensional reconstruction are helpful for visualizing complex osseous structures. Nevertheless, the most exciting advances regarding imaging of the temporal bone were achieved in MR imaging. Improvement of surface coil technology, application of gadopentetate dimeglumine, and development of new imaging sequences led to an increasing importance for MR imaging, especially in inflammatory diseases. Soft tissue structures in neoplastic diseases in the temporal bone are better depicted on MR imaging. Therefore, in some cases, both modalities are used to detect soft tissue and bony abnormalities of the temporal bone, especially for cases using surgical management. PMID- 1739588 TI - Imaging of the nasal cavity and paranasal sinuses. AB - The CT examination in the coronal plane is the optimal imaging modality to evaluate the nasal cavity and the paranasal sinuses, especially for evaluating chronic inflammatory disease. This modality affords optimal display of the osteomeatal channels and best defines the extent of mucoperiosteal disease. Updated parameters for scanning afford a significant reduction of radiation. MR imaging supersedes CT in its ability to distinguish between inflammatory and neoplastic pathology and appears to be the optimal imaging modality for diagnosis of fungal sinusitis. PMID- 1739589 TI - Imaging of the salivary glands. AB - Salivary gland diseases are very common disorders and require radiologic evaluation. Several radiologic methods are used for assessment of these diseases. Conventional films of the parotid and submandibular glands demonstrate opaque stones in the duct system, whereas sialography depicts nonopaque stones, provides additional information on the position of the stones, and differentiates it from other calcific densities near the duct system, as well as providing information concerning ectasia of the ducts. CT has been used for evaluating mass lesions and extraglandular inflammatory disease, including abscesses. CT also depicts stones that may not be visible on conventional films. MR imaging has become an important modality in the diagnosis and definition of benign and malignant tumors and cysts and it will probably replace CT as the primary imaging modality for the assessment of these lesions. Gadolinium may be used in the examination, especially if a malignant tumor is suspected (because of irregularity and intraglandular extension). PMID- 1739590 TI - Imaging of the larynx. AB - In the past year, most of the new developments in imaging the larynx have concerned MR imaging. Some early results with the use of gadolinium are very promising. The superiority of new imaging techniques (CT and MR imaging) for the evaluation of deep structures of the larynx is now widely accepted and there is now enough background to assess the impact of new imaging methods on treatment. Also, prognostic factors are now emerging in laryngeal cancer. CT and MR imaging appear to be of great interest for evaluating recurrent diseases. Interest in plain film studies still remains especially for emergency situations. In pediatric patients, ultrasound and ultrafast CT of the larynx have been investigated. PMID- 1739591 TI - Diagnostic procedures in nasopharyngeal illness. AB - The nasopharynx contains a wide variety of different cell types. Therefore, many kinds of lesions can occur in this area, ranging from embryologic abnormalities to benign and malignant neoplasms. The challenge to the radiologist is to describe the extent and localization of inflammation, benign, and malignant tumors. The diagnostic procedures in these cases include flexible or rigid fiberoptic clinical examinations. Pantomography and plain film studies are usually done as part of the initial examination, and CT replaces pluridirectional tomography for all questions about compact bone. Soft tissue extent of lesions is better shown on MR imaging. New scientific experiences in diagnosing lesions of the area of the nasopharynx are presented. PMID- 1739592 TI - Magnetic resonance techniques and artifacts. AB - One area in which MR imaging can use improvement is the reduction of artifacts due to various physiologic motions during imaging. These artifacts degrade images and can cause misleading interpretations. This paper reviews some of the recent technical advances directed to remove these artifacts, as well as other techniques that improve MR imaging quality in general. PMID- 1739593 TI - Imaging of the thyroid and parathyroid. AB - The radiologic armamentarium for imaging of thyroid and parathyroid diseases includes scintigraphy, ultrasonography, CT, and MR imaging. Continued refinements of these diagnostic tools have been made during the past year. This paper reviews those recent advancements in the fields of parathyroid and thyroid imaging. PMID- 1739594 TI - Temporomandibular joint imaging. AB - Pain and discomfort caused by internal derangement of the temporomandibular joint are frequent in our society. Patients can present with very divergent complaints, not always clearly related to the temporomandibular joint. Good imaging studies of the temporomandibular joint that can show the presence or absence of a problem and give an idea as to type of disease and its seriousness are, therefore, necessary. The choice of which imaging study to use largely depends on whether MR imaging is easily available. Ongoing investigations show that MR imaging of the temporomandibular joint not only depicts the soft tissue derangements very well, but also shows the associated bony changes. However, the exact significance of disk displacement is not always clear because anterior displacement is also seen in asymptomatic volunteers and after clinically successful treatment. PMID- 1739595 TI - Neuroradiology. PMID- 1739596 TI - Head and neck. PMID- 1739597 TI - Imaging of normal anatomy and anomalies of the brain. AB - Magnetic resonance imaging permits better delineation of many anatomic structures not resolved with other imaging modalities and, by permitting the behavior of these structures to be observed at different pulse sequences, allows their tissues to be characterized. The literature of the year 1990 to 1991 includes many descriptive reports of normal anatomy, some of which are accompanied by explanations for the MR signal appearance. Familiarity with normal central nervous system structures and with normal MR signal characteristics is essential to avoid mistaking them for pathologic variants. PMID- 1739598 TI - Imaging of pediatric and congenital brain disease. AB - The etiology of hemiplegic cerebral palsy has been elucidated by surveys of affected children using CT. MR imaging has contributed to the more exact diagnosis of the nature and extent of hypoxic ischemic damage and allows the accurate estimation of the time of the insult. Serial MR imaging and MR spectroscopy may be useful for predicting the prognosis for cerebral palsy and neurodevelopmental delay. The damage caused by intrauterine infection is best appreciated on MR imaging, though CT is important in showing calcification. Similar considerations apply to tuberous sclerosis, and new observations may facilitate MR imaging diagnosis. Gadolinium-enhanced MR imaging is the most accurate modality for detection of tumor recurrence and metastatic spread. Enhancement due to reactions to and complications of surgery can usually be distinguished. The reliability of MR imaging in showing many congenital anomalies provides evidence of the incidence of these lesions and contributes to understanding the disordered embryology. Most of the changes described in inherited metabolic disorders are nonspecific, but they may suggest a particular diagnosis, and MR imaging is the most sensitive modality for monitoring progress. Lifesaving intervention for arteriovenous malformations involving the vein of Galen requires detailed noninvasive imaging for selecting the most effective approach. Technical developments in diffusion and in flow imaging promise to further increase our diagnostic capabilities and to limit the application of invasive techniques. PMID- 1739599 TI - Magnetic resonance imaging contrast agents. AB - Intravenous contrast enhancement has assumed a prominent position in clinical MR imaging, particularly for studies of the head and spine. New chelates such as gadoteridol are likely to be approved in the near future; gadopentetate dimeglumine is the only agent approved for clinical use in the United States. Clinical applications have rapidly expanded for the gadolinium chelates with extracellular distribution. Within the next decade, approval is anticipated for a variety of additional agents that may help assess tissue function. PMID- 1739600 TI - Imaging of metabolic diseases of the brain. AB - Increasing interest in metabolic diseases of the brain has revealed more specific patterns of disease, permitting us to make more accurate diagnoses or to suggest a more limited differential list of considerations. MR imaging is also useful in monitoring the course of the disease in processes for which treatment is available. PMID- 1739601 TI - Imaging of infections of the central nervous system. AB - Acquired immunodeficiency syndrome (AIDS) and AIDS-related infection of the brain constitute a large fraction of the most recent research into central nervous system infection. Two major areas of controversy discussed in the past year's literature were the neuroradiologic and neurologic manifestations of early human immunodeficiency virus infection in the central nervous system and differentiation of toxoplasmosis from lymphoma. Other non-AIDS related infections discussed included infectious aneurysms, bacterial abscesses, tuberculosis, cysticercosis, fungal infections, and zoster myelitis. PMID- 1739602 TI - Imaging of tumors of the central nervous system. AB - Research in diagnosing and understanding brain tumors in neuroradiology is influenced by the investigative tools available to neuroradiologists. CT has represented the gold standard for the past two decades. The role of angiography has become complementary; relevant in the therapeutic phase of embolization of meningiomas or base of the skull tumors or in intra-arterial chemotherapy for gliomas. In 1991, the MR imaging revolution continues to provide new insights in the diagnosis, classification, and understanding of the biology of brain tumors. Interest has been focused mainly on information provided by MR imaging and MR spectroscopy. Spectroscopy is being used in a more systematic way and in large series with different histologic tumor types. Spectra from tumors are definitely different from those of normal brain, although no specific patterns for histologic types were found, with the possible exception of meningiomas. Comparison with positron emission tomography is considered to be useful. Analysis of rare tumors using MR imaging allows better understanding, classification, diagnosis, and surgical therapy of lesions such as central neurocytomas, hamartomatous tumors, and lymphomas. An attempt at a better classification for brain tumors was proposed and may prove to be very useful for systematization and communication. PMID- 1739603 TI - Imaging of degenerative processes of the spine. AB - Because MR imaging provides accurate, clear, and noninvasive imaging for diseases of the spine and spinal cord, it has become the primary imaging modality in patients with spinal pathology. Degenerative processes of the spine are frequent, including disk degeneration and herniations, spondylosis, spinal canal stenoses, calcifications, and ossifications of the spinal ligaments. Several papers have been published recently on MR imaging in degenerative processes of the spine. PMID- 1739604 TI - Ischemic brain disease, vascular brain disease, and magnetic resonance angiography. AB - Rapid, accurate diagnosis and successful implementation of new stroke therapies will depend on the refinement and skilled use of neuroimaging. Because a variety of MR techniques offer information on local brain biochemistry, blood flow, perfusion, vascular integrity, ischemia, edema or free water, infarction, and hemorrhage, there is intense interest in their application to cerebrovascular disease. This review highlights recent advances in MR technology as they relate to conventional MR imaging, MR angiography, and basic MR research into the use of diffusion, perfusion, and spectroscopic techniques. PMID- 1739605 TI - Imaging of neurodegenerative diseases. AB - Neuroimaging of degenerative brain disorders has continued to advance, primarily with MR imaging, single-photon emission CT, and positron emission tomography. Information gained from these morphologic and functional imaging studies provides insight into the pathologic and pathophysiologic changes associated with these diseases. Recent papers relating to various neurodegenerative disorders such as Alzheimer's disease, vascular dementias, acquired immunodeficiency syndrome related dementia, Pick's disease, Huntington's disease, progressive supranuclear palsy, and others are reviewed and discussed. PMID- 1739606 TI - Physiologic imaging of the brain. AB - Advances in imaging hardware for positron emission tomography and single-photon emission CT, coupled with a wide variety of radiopharmaceutical agents, have allowed these techniques to be used in the evaluation of neoplasm, stroke, epilepsy, and dementia. Cerebral perfusion agents continue to be the mainstay of single-photon emission CT imaging but, in addition to the evaluation of ischemia, it has seen an increasing role in the study of dementia, neuropsychiatric disorders, and seizures. Positron emission tomography scanning has had similar applications but it is playing a greater part in the evaluation of neoplasms, including primary gliomas and pituitary adenomas. Stable-xenon CT has shown value in the study of ischemia associated with meningitis, sickle cell disease, chronic subdural hematomas, and cerebral arteriovenous malformations. MR diffusion imaging shows promise in the evaluation of white matter pathology and some tumors. PMID- 1739607 TI - Selectivity and potency; are we doing the right things to find anti-cancer agents with these properties? PMID- 1739608 TI - The management of locally advanced breast cancer. PMID- 1739609 TI - Lessons from 20 years of curative therapy of childhood acute leukaemia. AB - The past 20 years of curative therapeutics of childhood acute leukaemia has been largely a period of consolidation of gains, refinement of techniques and dissemination of expertise and technology. However, certain lessons have been learned. First, cure can be permanent but the complexity and cost of curative treatment currently restricts its accessibility; prevention or simple curative treatment is needed. Secondly, cure of the child demands that the risk of adverse sequelae of treatments be carefully balanced with known therapeutic benefits. Thirdly, preventive meningeal irradiation is no longer required. Fourth, treatment intensification is self-limiting. Adverse reactions can cancel out or exceed therapeutic benefits, resulting in a lower cure rate or a similar cure rate with lower quality of cure. Finally, morphology, immunophenotype and genotype of acute leukaemia are important criteria for selecting and scheduling drug therapy. Genotype may be the most important since leukaemia is a genetic disorder for which morphology and immunophenotype are mere reflections. However, none of these features, individually or together, are sufficient to explain all the difference in outcome among children on a given treatment plan or to completely fulfill the need of criteria for selection of treatment. Acute leukaemia remains an unsolved problem demanding considerably more basic and clinical research to meet the need for prevention and simple dependable curative treatment. PMID- 1739610 TI - Enhancement of transforming growth factor-alpha synthesis in multicellular tumour spheroids of A431 squamous carcinoma cells. AB - Multicellular tumour spheroids are cellular aggregates that can be prepared from many types of tumour cells. These three-dimensional structures provide a model for analysing the effects of cell-cell contact and intercellular microenvironments on phenomena such as autocrine regulation of growth factor synthesis. Autoregulation of the synthesis of transforming growth factor-alpha (TGF-alpha) was investigated at the message and protein levels in spheroid and monolayer cultures prepared from the A431 human squamous carcinoma cell line. The epidermal growth factor receptor (EGF-R) of these monolayer A431 cells had an average surface density of 2.2 x 10(6)/cell. Constitutive expression of TGF-alpha mRNA was an average of 3-fold greater in A431 spheroids than in monolayers, even for densely packed, confluent monolayers. This effect did not depend on hypoxic stress within the spheroids. TGF-alpha protein synthesis was enhanced in comparison with that in monolayer culture, reaching a value of up to 2-fold greater on a per cell basis. These results are discussed in the context of a TGF alpha/EGF-R autocrine loop operating within cells that produce high local concentrations of TGF-alpha in the three-dimensional architecture of a spheroid. PMID- 1739611 TI - Changes in tissue fatty acid composition in murine malignancy and following anticancer therapy. AB - We studied the mouse NC tumour, a subcutaneously transplanted adenocarcinoma originally of mammary origin. Measurements per g tissue were made of 17 fatty acids (FAs), the combined amounts of n-3, n-6, saturated, unsaturated, and total FAs, and of various FA ratios in the tumour, mammary tissue, spleen, liver and plasma. Compared with mammary tissue from normal mice, tumours of vehicle-treated controls had less of seven of the FAs and more of two FAs. Mice bearing the NC tumour often had changed (usually decreased) amounts of FAs in the 'normal' spleen, liver and plasma, but not in mammary tissue. Treatment with methotrexate (MTX) was studied alone and with indomethacin which can potentiate MTX cytotoxicity. Indomethacin 1.25 mg kg-1 (INDO) increased the amounts of 3/17 tumours FAs and the unsaturated FAs, but reduced 9/17 FAs, the saturated and the unsaturated FAs in 'normal' mammary tissue, and usually had no effect on the FAs of other tissues. MTX 2 or 4 mg kg-1 (MTX 2 or 4 mg) +/- INDO in general partly restored (increased) the amounts of tumour FAs, and reduced the saturated/unsaturated FA ratio. In the 'normal' spleen and plasma also, but not in the liver, MTX 2 mg generally somewhat restored the FA composition. However, as in the liver, the spleen 20:4 and 22:6 (which form prostaglandins and lipid peroxides) did not increase in the presence of INDO. With MTX 4 mg, some of the plasma and liver FAs decreased, in contrast to the tumour. There was generally no evidence of MTX potentiation by INDO. These results are discussed in relation to carcinogenesis, cachexia, and the response to treatment. PMID- 1739612 TI - The inhibition of DNA synthesis in chronic lymphocytic leukaemia cells by chlorambucil in vitro. AB - The inhibition of 3H-thymidine incorporation into the DNA of mitogen-stimulated lymphocytes from patients with chronic lymphocytic leukaemia by chlorambucil was measured in vitro and the results related to clinical drug resistance. The assay proved to be both sensitive and specific showing a clear separation of those patients with responsive disease from those with disease resistant to treatment. There was evidence of primary drug resistance in untreated patients. In almost all patients who received treatment this led to increasing resistance to chlorambucil in vitro. The assay is predictive of clinical responsiveness and provides a potential means whereby new therapeutic agents and treatment modifiers may be investigated. PMID- 1739613 TI - Divergent responses to epidermal growth factor in hormone sensitive and insensitive human prostate cancer cell lines. AB - The present study was undertaken to compare the relationship between response to exogenous epidermal growth factor (EGF) and the expression of the EGF-receptor (EGF-R) in an androgen sensitive (LNCaP) and insensitive (DU145) prostate cancer cell line. Although both cell lines demonstrated a single EGF-R binding site of similar high affinities (mean dissociation constant (Kd) +/- S.D. for DU145 = 1.0 +/- 0.6 nmol l-1; LNCaP = 2.8 +/- 2.2 nmol l-1) the number of binding sites (RT) for the hormone insensitive DU145 cells (mean +/- S.D. = 2.5 +/- 1.0 x 10(5) sites/cell) and 10-fold greater than that expressed in the androgen responsive LNCaP cell line (mean +/- S.D. = 2.0 +/- 1 x 10(4) sites/cell). Additionally exogenous EGF only minimally affected the growth and DNA synthesis of DU145 cells whereas LNCaP cells showed a significant response which was dose dependent. The autologous production of EGF-like molecules by DU145 cells is believed to reduce the cells needs for exogenous mitogens, thereby rendering the cells autostimulatory. Treatment of LNCaP cells with Mibolerone--a synthetic androgen- did not affect either the expression of the EGF receptor or the proliferative response observed with EGF. Western blot analysis, using monoclonal antibodies directed against the EGF receptor revealed a band of approximately 170 kD with DU145 cell lysates but the LNCaP EGF receptor was not detected using this technique. PMID- 1739614 TI - Novobiocin-induced anti-proliferative and differentiating effects in melanoma B16. AB - The antibiotic drug novobiocin was evaluated for its anti-tumour properties in B16 melanoma cells. Novobiocin is shown to inhibit melanoma B16 cell proliferation. The anti-proliferative effect was gradually reversible upon removal of novobiocin from the culture medium. Growth inhibition by novobiocin was accompanied by phenotypic alterations, that included morphological changes, lipid accumulation and marked increases in the activities of NADPH cytochrome c reductase and gamma glutamyl transpeptidase. In vivo administration of repeated i.p. doses of novobiocin, to mice implanted with B16 melanoma cells resulted in growth retardation. The combined treatment of the B16 melanoma cells with novobiocin and other chemical inducers of differentiation was examined in a cell growth assay. Novobiocin and sodium butyrate inhibited cell growth in a near additive manner, while combination of novobiocin with the GTP-depleting agents, tiazofurin or mycophenolic acid resulted in a synergistic decrease in cell growth. Our results support the contention further that novobiocin and other differentiating agents might be of potential value in melanoma therapy. PMID- 1739615 TI - Epidermal growth factor receptor levels are lower in carcinomatous than in normal colorectal tissue. AB - A series of 24 paired samples of colorectal carcinoma and the respective normal colorectal mucosa were analysed for Epidermal Growth Factor Receptor (EGFR) content by means of a standardised ligand binding assay. We, for the first time, found that EGFR levels are statistically significantly higher in normal colorectal mucosa biopsy samples than they are in colorectal carcinoma biopsy samples, the median EGFR levels being 77.5 fmol mg-1 of membrane protein (range 35-239), against 46 fmol mg-1 of membrane protein (range 22-81), respectively, P less than 0.001. In addition, we found that there are significant regional differences in EGFR expression in the normal human colon mucosa. The EGFR levels were significantly higher in samples from the proximal part of the colon than they were in samples from the distal part, the median EGFR levels being 124 fmol mg-1 of membrane protein (range 70-239) vs 55 fmol mg-1 membrane protein (range 35-156), P less than 0.05. The EGFR levels of the colorectal carcinoma samples did not show any regional variation. PMID- 1739616 TI - Type III collagen metabolism in soft tissue sarcomas. AB - Sera of 85 patients with benign soft tissue lesions or sarcomas of soft tissues were investigated for a collagen metabolite, the aminoterminal propeptide of type III procollagen (PIIINP). Patients were divided into three groups: benign soft tissue lesions (n = 39), localised (n = 29) and metastatic (n = 18) soft tissue sarcomas (STS). Values of PIIINP above the reference range were found in 15%, 28% and 50% of the respective groups. The difference in the concentration of PIIINP was statistically significant between the benign lesions and the localised sarcomas; P = 0.05, and between the benign lesions and the metastatic sarcomas; P less than 0.001. In localised sarcomas there was a correlation between PIIINP and bone-involvement (r = 0.61, P = 0.002) and in metastatic disease between PIIINP and liver metastases (r = 0.77, P less than 0.001). In localised sarcomas the overall survival for patients with a value of PIIINP above the reference range was significantly poorer (P = 0.03) than for patients with values within the reference range, even after stratification for the histological malignancy grade of the tumours (P = 0.04). PMID- 1739617 TI - Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA). AB - Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human/mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fc portion and/or CH1 or CL region of murine IgG, and (2) human/mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients. PMID- 1739618 TI - Production and characterisation of a monoclonal antibody (Cx-99) against cervical carcinoma. AB - An IgG1 monoclonal antibody (MAb Cx-99) has been established which recognises a surface antigen on epithelial cells, but not on fibroblastic or hematopoietic cells. Immunohistochemical studies showed that this antigen was present in all 37 squamous cell carcinomas (SCC) including 33 cervical SCC, and 30 of the 32 adenocarcinomas examined; most of the 33 cervical SCC were stained extensively. It was also detected in the culture medium of cervical cancer cell lines. In the normal cervix, this antigen was restricted to the undifferentiated basal cells. This observation suggests that the widespread expression of the antigen was triggered by oncogenesis. The MAb Cx-99 recognised an epitope on an asialyted glycoprotein which has an apparent molecular weight of 37 kilodaltons (kD) (and 2 minor proteins at 18 and 27 kD) and an isoelectric point (pI) of 5.3. It may have potential for studies on differentiation and oncogenesis and for diagnostic applications. PMID- 1739619 TI - Inactivation of p53 gene in human and murine osteosarcoma cells. AB - We examined structure and expression of the p53 and Rb genes in a C3HOS transplantable mouse model of osteosarcoma. The results were compared to analogous studies conducted with five human osteosarcoma cell lines. The p53 gene was found rearranged in the mouse tumour. The rearrangement mapped to the first intron region of the p53 gene and as a result, no p53 expression could be detected in C3HOS tumours. Using p53 genomic probes, we have detected the same rearrangement in the original radiation-induced tumour and the various clones that were isolated from it. Deletion and rearrangement of the p53 gene were also found in three out of five of the human osteosarcoma cell lines (MG-63, G-292, Saos-2). No p53 expression could be detected in these three cell lines. In the affected human osteosarcoma cell lines, the rearrangement involved the first intron region. In addition, the mouse tumor was analysed for structural and expression changes in the Rb and the c-myc genes. Normal expression of both genes were detected in the murine tumour. Only one (Saos-2) human osteosarcoma cell line exhibited gross structural alteration in the retinoblastoma gene. The results suggest that the inactivation of p53 may be an important step in the development of osteosarcomas, and that a rearrangement affecting the first intron is common in osteosarcomas. PMID- 1739620 TI - Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9. AB - A serological assay for the quantitative determination of the novel tumour associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer. PMID- 1739621 TI - Generation of adherent lymphokine activated killer (A-LAK) cells from patients with acute myelogenous leukaemia. AB - Successful generation of adherent lymphokine-activated killer (A-LAK) cells, highly-enriched in CD3-CD56+ antitumour effector cells, from the peripheral blood of ten patients with acute myelogenous leukaemia (AML) is described. The AML patients were either untreated or in remission. In vitro proliferation of A-LAK cells in patients with AML was generally poor, unless the cells were cocultured with irradiated concanavalin A (ConA)--prestimulated allogeneic PBL or selected lymphoblastoid cell lines (LCL) as feeder cells. Using this method, the median fold proliferation was 290 for A-LAK cells cultured with ConA-activated feeders and 291 for those grown with LCL, both significantly higher (both P less than 0.001) than the median of 2-fold expansion observed in cultures without feeders. A-LAK cultures generated in the presence of feeders consistently showed good enrichment (up to 90%) in CD3-CD56+ NK cells. Although NK activity was not significantly increased on a per cell basis in A-LAK cells grown with feeder cells, total lytic activities against both NK-sensitive target, K562, and NK resistant target, Daudi, were significantly greater (P less than 0.02 for ConA PBL feeders and P less than 0.005 for LCL feeders) as compared to those in paired cultures without feeders. In the presence of irradiated allogeneic feeder cells, 7/10 AML patients generated A-LAK cultures characterised by good proliferation and increased purity as well as cytotoxic activity. PMID- 1739622 TI - In vitro and in vivo studies on the combination of Brequinar sodium (DUP-785; NSC 368390) with 5-fluorouracil; effects of uridine. AB - Brequinar sodium (DUP-785; Brequinar) is a potent inhibitor of the pyrimidine de novo enzyme dihydroorotate dehydrogenase (DHO-DH), leading to a depletion of pyrimidine nucleotides, which could be reversed by uridine. In in vitro studies we investigated the effect of different physiological concentrations of uridine on the growth-inhibition by Brequinar, the effect of the nucleoside transport inhibitor, dipyridamole, and the combination of Brequinar and 5-fluorouracil (5FU). Uridine at 1 microM slightly reversed the growth inhibition by Brequinar, while the effect of 5-500 microM was greater. However, at Brequinar concentrations greater than 30 microM, uridine could not reverse the growth inhibitory effects. Addition of dipyridamole could only partially prevent the reversing effects of uridine. The combination of Brequinar and 5FU was more than additive in the absence of uridine in the culture medium, but not in the presence of uridine. The combination of Brequinar and 5FU was tested in vivo in two murine colon tumour models, Colon 26 and Colon 38. Scheduling of both compounds appeared to be very important. In Colon 38 no potentiating effect of Brequinar could be observed. In contrast in Colon 26 a more than additive effect could be observed. Since uridine concentrations are considerably different in these tumours (higher in Colon 38), it was concluded from both the in vitro and in vivo experiments that uridine is an important determinant in combinations of Brequinar and 5FU. PMID- 1739623 TI - Molecular and functional characterisation of a fusion protein suited for tumour specific prodrug activation. AB - A fusion protein consisting of the humanised Fab fragment of the anti CEA MAb BW 431 and the human beta-glucuronidase was expressed in BHK cells. Functional testing revealed that the specificity and avidity of the humanised V region was similar to the original murine MAb BW 431. Furthermore, the enzymatic activity, pH sensitivity and stability of the human beta-glucuronidase in the fusion protein was comparable to the activity of recombinant human beta-glucuronidase. Using anti-idiotype affinity chromatography, two molecules of a molecular weight of 125 kDa or 250 kDa could be visualized under nonreducing conditions in SDS PAGE. Reducing conditions revealed a 25 kDa light and 100 kDa heavy chain. Due to its suitable biological characteristics this fusion protein might be an appropriate molecule allowing a site specific antibody directed enzyme prodrug therapy (ADEPT) in vivo. PMID- 1739624 TI - Detection of bone marrow abnormalities in patients with Hodgkin's disease by T1 mapping of MR images of lumbar vertebral bone marrow. AB - Pixel by pixel T1 mapping of MR images has been used in conjunction with image analysis techniques to study the lumbar vertebral bone marrow of 20 patients with refractory or relapsed Hodgkin's disease prior to salvage chemotherapy, or high dose chemotherapy with autologous bone marrow rescue. Compared to 18 age matched controls, seven patients had significantly abnormal lumbar vertebral marrow T1 histograms with median, 5% and 95% centile T1 values that lay outside a three dimensional 95% probability region obtained for the normals. Six of these patients had increased areas of high T1 consistent with bone marrow involvement with lymphoma; although, only in two of them had Hodgkin's disease been detected by bilateral iliac crest bone marrow biopsy. Post-treatment studies were performed in four patients who had abnormal areas of high T1 in the lumbar vertebral bone marrow. All showed normalisation of the T1 histogram, with a reduction of T1 values to within the normal range as defined by the studies of age matched controls. T1 mapping of bone marrow offers potential for detecting bone marrow infiltrates in patients with lymphoma, and also for the assessment of treatment response. PMID- 1739625 TI - Adjuvant tamoxifen for male breast cancer (MBC). AB - A study was started in 1976 whereby patients with Stage II and operable Stage III MBC were given adjuvant Tamoxifen for 1 year, increasing to 2 years from 1988. All patients had axillary nodal involvement. Primary treatment consisted of a radical mastectomy or simple mastectomy with radiotherapy. The rarity of the disease precluded a randomised trial. Thirty-nine patients are available for analysis at a median follow-up of 49 months. The actuarial survival of the Tamoxifen treated patients is 61% (range 42-80%) at 5 years compared to 44% (range 35-53%) for historical controls (P = 0.006). Disease-free survival was 56% (37-75%) vs 28% (17-33%) at 5 years (P = 0.005). There were no serious side effects recorded. The conclusion from this, the first reported series on adjuvant Tamoxifen therapy for MBC, is that significant improvement in disease-free survival can be achieved with minimal upset to the patients. Recruitment to the study continues. PMID- 1739626 TI - Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. AB - Forty-two families with two or more cases of testicular cancer have been reported to the UK Register for Familial Testicular Cancer, comprising two pairs of identical twins, 27 sets of other brothers (25 pairs, two triples), nine father son pairs, two pairs of first cousins and two uncle-nephew pairs. In total 91 testicular tumours are described in 86 individuals (42 (46%) pure seminoma, 49 (54%) other germ cell tumours). The median age at diagnosis in these patients was significantly younger than that in a comparable series of non-familial patients (29 c.f. 32.5 years, P less than 0.01). In a case-control comparison of 794 testicular cancer patients, eight patients (1.0%) had a brother and four patients (0.5%) had a father with a previous diagnosis of testicular cancer at the time of their own diagnosis (and these families are all included in this report). Two out of 794 controls (0.3%) had a first degree relative with testicular cancer. The cumulative risk to a brother of a patient for developing testicular cancer by the age of 50 years was estimated to be 2.2% (95% C.I. 0.6-3.8%) which results in a relative risk of 9.8 (95% C.I. 2.8-16.7) in comparison with the general population. HLA Class I typing of 21 affected sib-pairs demonstrated four (19%) sharing two haplotypes, 13 pairs (62%) sharing one and four pairs (19%) sharing none. This did not differ significantly from the expected proportions of 25%/50%/25%. It is unlikely, therefore, that there is a major gene associated with testicular cancer predisposition within or closely linked to the major histocompatibility gene complex on chromosome 6. PMID- 1739627 TI - A case-control study of cancers of the gastric cardia in Italy. AB - In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7 fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries. PMID- 1739628 TI - A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide. AB - Multidrug resistance (MDR) is one of the mechanisms of resistance to multiple cytotoxic drugs and is mediated by the expression of a membrane pump called the P glycoprotein. Nifedipine is one of the calcium channel blocking agents which reverses MDR in vitro. Fifteen patients with various malignancies received nifedipine at three dose levels: 40 mg, 60 mg and 80 mg orally twice daily for 6 days. Etoposide was administered intravenously on day 2 in a dose of 150-250 mg m 2 and orally 150-300 mg twice daily on days 3 and 4. Cardiovascular effects of nifedipine were dose limiting and the maximum tolerated dose was 60 mg bid. Mean area under the plasma concentration curve (AUC0-00) and plasma half-life (beta) of nifedipine and its major metabolite MI at the highest dose level were 7.87 microM.h, 7.97 h and 4.97 microM.h, 14.0 h respectively. Nifedipine did not interfere with the pharmacokinetics of etoposide. PMID- 1739629 TI - A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer. AB - A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts. PMID- 1739630 TI - Prognostic impact of chromosome aberrations in ovarian cancer. AB - Clinico-cytogenetic correlations were assessed in 88 patients with malignant ovarian tumours. Cytogenetic analysis of the primary tumours yielded normal karyotype (N) in 33 patients and abnormal karyotypes (A) in 55 patients. Within the A group, seven tumours had simple abnormalities (AS), i.e., numerical changes only or a single structural aberration, and 48 had karyotypes with complex aberrations (AC). A correlation analysis between groups N and A revealed that cytogenetic abnormalities were more often found among seropapillary tumours, and that cases with abnormal karyotypes on average were of higher stage and more often had residual tumour mass after initial surgery (P less than 0.05 for all variables). When the three groups N, AS, and AC were compared, they were found to be significantly different with regard not only to the three parameters mentioned above, but now tumour grade also appeared to correlate with karyotypic pattern (P = 0.001), with poorly differentiated tumours having the most complex karyotypes. In a correlation analysis between karyotypic pattern and survival, group A patients had shorter survival than group N (P = 0.049). In the corresponding analysis between groups N, AS, and AC, the differences were also significant (P = 0.039), with shorter survival in group AC than in groups N and AS. Stage, grade, residual tumour after primary surgery, and performance status also correlated with survival time. A multivariate analysis identified abnormal karyotype as being independently associated with short survival in advanced clinical stages (P = 0.030) of ovarian carcinoma. We conclude that cytogenetic analysis of tumour cells may be of clinical value in the assessment of prognosis in patients with malignant ovarian tumours. PMID- 1739631 TI - Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). AB - Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide. PMID- 1739632 TI - Serum ceruloplasmin and the risk of cancer in Finland. AB - The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer. PMID- 1739633 TI - Neuron-specific enolase--a serum tumour marker in seminoma? AB - The clinical significance of neuron-specific enolase (NSE) as a tumour marker was evaluated in 54 patients with seminoma. Before orchiectomy NSE was elevated in six out of 21 patients with stage I seminoma and 11 out of 16 patients with metastases. After orchiectomy NSE normalised in all evaluated stage I cases, but was still elevated in six out of 12 patients with metastatic disease. NSE monitored the effect of cisplatin-based chemotherapy in patients with metastases. In some patients, increased serum NSE was found together with raised levels of human choriogonadotropin (HCG) and lactate dehydrogenase (LDH), while in others only NSE was elevated. No false positive NSE values were observed. NSE seems to be a clinically worthwhile serum tumour marker for monitoring seminoma patients, with a sensitivity and specificity of the same order as HCG. PMID- 1739634 TI - An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis. AB - Expression of alpha-1-antitrypsin (AAT) in tumour cells of 102 surgically resected lung adenocarcinomas was examined by immunohistochemical method using anti-AAT antiserum. While only 13 cases (13%) were negative for AAT expression, 89 cases (87%) contained AAT at varying degrees. The degree of AAT-positive tumour cells was significantly higher in advanced cases than in early cases. Clinical follow-up study of the patients, particularly in stage I, showed that strongly AAT-positive cases have poor prognosis than weak-to-moderately AAT positive or AAT-negative cases. Thus, AAT expression status in tumour cells of lung adenocarcinoma may be a biological marker of prognostic significance in regard to tumour growth. PMID- 1739635 TI - Dacarbazine (DTIC), human recombinant interferon alpha 2a (Roferon) and 5 fluorouracil for disseminated malignant melanoma. PMID- 1739636 TI - Beta-hCG expression by bladder cancers. PMID- 1739637 TI - School nursing: more than a mother substitute. Interview by Daniel Allen. PMID- 1739638 TI - Practice nursing--an auspicious future. PMID- 1739639 TI - Operation clean-up. Cleaning up our act. PMID- 1739640 TI - Operation clean-up. Cleaning up. PMID- 1739641 TI - Operation clean-up. The real cost. PMID- 1739642 TI - Operation clean-up. Hands up for cleanliness. PMID- 1739643 TI - Children with cancer: supporting the family. PMID- 1739644 TI - Psychiatry. Hospital closure: a personal experience. PMID- 1739645 TI - Cleaner hospitals. PMID- 1739646 TI - Psychiatry. Nurses' reactions to hospital closure. AB - The second article dealing with the effects of psychiatric hospital closure explores how the transition from the role of hospital nurse to community nurse occasioned by closure is proving an extremely difficult process. Some of the feelings evoked resemble the grief experienced after the death of a loved one. This article focuses on the reactions of 22 nurses to the closure of a large mental hospital. Nurses with many years' experience were found to be suffering a bereavement reaction which threatened their emotional and physical wellbeing. The author suggests that this 'institutional loss' has important implications for the successful rehabilitation of large numbers of mentally ill patients. PMID- 1739647 TI - Continuing education: who meets the cost? PMID- 1739648 TI - Linking students with ambulance teams. PMID- 1739650 TI - Attitude towards the care of elderly people. PMID- 1739649 TI - Time to end the violence. PMID- 1739651 TI - Professional conduct: left out in the Code? PMID- 1739652 TI - Ethics: upward accountability. PMID- 1739653 TI - A day in the life: a job at holidaymakers. PMID- 1739655 TI - Pleasure time? PMID- 1739654 TI - Spare us the yuppie nurse. PMID- 1739656 TI - Mental health: a nurse for all reasons. PMID- 1739657 TI - Ethics: grass on patients? PMID- 1739658 TI - Quality care: abusing drug users. PMID- 1739659 TI - Nurse leaders: Hunt at the helm. Interview by Norah Casey. PMID- 1739660 TI - Continuing education: leading from the front. Interview by Norah Casey. PMID- 1739661 TI - Operation clean-up. Sweeping changes. PMID- 1739662 TI - Absorption and function of iron. PMID- 1739663 TI - Operation clean-up. Urinary catheters: patient management. PMID- 1739664 TI - Educating nurses for practice in Europe. PMID- 1739665 TI - Implications of fetal cell transplantation. PMID- 1739666 TI - Supporting bereaved relatives in A&E. PMID- 1739667 TI - State of hospitals in the United Kingdom. PMID- 1739668 TI - Ethics: measuring life in pounds. PMID- 1739669 TI - Operation clean-up. Hygiene--your legal rights. PMID- 1739670 TI - Equal opportunities: artificial sexuality. PMID- 1739671 TI - Whistleblowing: the case for confidentiality. PMID- 1739672 TI - Shift patterns: a hard day's night. PMID- 1739673 TI - Practice: individual and unique? PMID- 1739674 TI - Inward rectification in Limulus ventral photoreceptors. AB - We examined inward rectification in Limulus ventral photoreceptors using the two microelectrode voltage clamp. Hyperpolarization in the dark induced an inward current whose magnitude was distinctly dependent on extracellular K+ concentration, [K+0]. The [K+0] dependence resembled the characteristic [K+0] dependence of other inward rectifiers. The inward current was not dependent on extracellular Ca2+ or Na+, and it was unaffected by intracellular injection of Cl . The hyperpolarization induced currents had two phases, an early nearly instantaneous phase and a slowly developing late phase. The currents were sensitive to extracellular barium and cesium. In voltage-pulse experiments, the magnitudes of the inwardly rectifying currents were variable from cell to cell, with some cells exhibiting negligible inward currents. Large hyperpolarizations (to membrane potentials more negative than about -140 mV) caused unstable inward current recordings, irreversible desensitization, and irreversible elevation of intracellular Ca2+ concentration. The inward rectifier provides negative feedback by tending to depolarize the cell (with inward current) in response to hyperpolarization. We suggest that the inward rectifier reduces the amount of hyperpolarization that would otherwise be generated by electrogenic processes. This feature would restrict the dynamic voltage range of the photoreceptors at very hyperpolarized potentials. PMID- 1739675 TI - Foveal dark adaptation, photopigment regeneration, and aging. AB - Foveal dark adaptation in 58 subjects and photopigment regeneration in 60 subjects from 10-78 years of age exhibit parallel slowing of recovery rate with increasing age, with significant correlation of the two functions among individuals. The data are suggestive of an initial slight decline in rate before age 50, followed by a greater decline occurring at different ages in different individuals. Longitudinal data for one subject from age 40-65 show an increase in pigment regeneration time constant consistent with this idea. Foveal sensitivity and photopigment density both decrease with increasing age and are significantly correlated among individuals, although sensitivity declines more with age than does photopigment density. In contrast to earlier proposals based upon the Rushton-Dowling equation, we found no universal constant of proportionality to relate log relative threshold to photopigment within our population. PMID- 1739676 TI - Development of lateral interactions in the infant visual system. AB - The development of lateral inhibitory interactions in the infant visual system, as reflected by the visual-evoked potential (VEP), was studied using a radial, asymmetrical windmill-dartboard stimulus. This contrast-reversing stimulus generates VEP responses with a strong fundamental frequency component and an attenuated second harmonic component (relative to that obtained using a symmetrical stimulus). These two harmonic components reflect distinct phenomena, and appear to be the result of short-range (the fundamental) and long-range (attenuated second harmonic) lateral inhibitory interactions elicited by differential luminance-modulation of contiguous spatial regions. We studied the development of the short- and long-range interactions at 100% and 30% contrast in human infants using both VEP amplitude and phase measures. Attenuation of the second harmonic (long-range interactions) was adult-like by 8 weeks of age while the strength of the fundamental (short-range interactions) was adult-like by 20 weeks suggesting a differential development of long-range and short-range interactions. In contrast, corresponding phase data indicated significant immaturities at 20 weeks of age for both the short- and long-range components. PMID- 1739677 TI - Localization of phototransduction in Limulus ventral photoreceptors: a demonstration using cell-free rhabdomeric vesicles. AB - Second messengers are involved in a number of cellular responses to a variety of stimuli. Diffusion of these second messengers likely will determine the speed and efficiency of such responses. Localization, particularly in large cells, would enhance the efficiency of such transduction systems by restricting the volume in which this diffusion takes place and thereby limiting the diffusion of soluble messengers. Phototransduction in Limulus ventral photoreceptors involves second messenger systems; the volume of this cell is quite large, but the effect of a single photoexcited rhodopsin molecule is exerted over light-dependent channels localized within a very small area of the plasma membrane. In order to investigate localization of phototransduction in these photoreceptors, we have compared the light responses of small vesicles (photoballs) excised from these cells with those of the intact photoreceptors. We found that the basic kinetics of excitation and adaptation of the photoballs are essentially identical to those of the intact cell. This indicates that all of the necessary machinery for phototransduction is present and intact in the photoball and that any diffusion of second messengers that affect the normal light response of the cell must occur within a region at least as small as our photoballs (on the order of 1 micron3). PMID- 1739678 TI - Transfer of contrast sensitivity in linear visual networks. AB - Contrast sensitivity is a useful measure of the ability of an observer to distinguish contrast signals from noise. Although usually applied to human observers, contrast sensitivity can also be defined operationally for individual visual neurons. In a model linear neuron consisting of a filter and noise source, this operational measure is a function of filter gain, noise power spectrum, signal duration, and a performance criterion. This definition allows one to relate the sensitivities of linear neurons at different levels in the visual pathway. Mathematical formulae describing these relationships are derived, and the general model is applied to the specific problem of relating the sensitivities of parvocellular LGN neurons and cortical simple cells in the primate. PMID- 1739679 TI - Acid phosphatase localization in endocytosed horizontal cell gap junctions. AB - Gap junction (GJ) endocytosis appears to be part of a cycle of GJ renewal in horizontal cells of the teleost fish retina. At least three stages of GJ endocytosis in these neurons have been identified using conventional electron microscopy (EM): invagination of GJ membranes (GJ blebs); free GJ vesicles; and GJ vesicle fusion with mature lysosomes (Vaughan & Lasater, 1990a). In the present study, EM-level acid phosphatase (AP) histochemistry of white bass retina was used to determine at what stage enzymatic degradation of endocytosed GJs begins. Electron-dense AP reaction product was observed within the trans face of the Golgi apparatus, mature lysosomes, and occasional, internal GJ vesicles. In contrast, GJ blebs, peripheral GJ vesicles, and most internal GJ vesicles lacked AP reaction product. These results support the idea that at least some of the GJ vesicles observed within these retinal neurons arise from endocytosis, are on a degradative pathway, and can be termed GJ "endosomes." Furthermore, GJ vesicles appear to be initially free of AP, but some later acquire it (presumably from transport vesicles bearing degradative enzymes). It is still unclear whether our previous report of GJ vesicle fusion with mature lysosomes is a subsequent step in GJ degradation or part of a different degradative pathway altogether. PMID- 1739680 TI - Light-dependent delay in the falling phase of the retinal rod photoresponse. AB - Using suction electrodes, photocurrent responses to 100-ms saturating flashes were recorded from isolated retinal rods of the larval-stage tiger salamander (Ambystoma tigrinum). The delay period (Tc) that preceded recovery of the dark current by a criterion amount (3 pA) was analyzed in relation to the flash intensity (If), and to the corresponding fractional bleach (R*0/Rtot) of the visual pigment; R*0/Rtot was compared with R*s/Rtot, the fractional bleach at which the peak level of activated transducin approaches saturation. Over an approximately 8 ln unit range of I(f) that included the predicted value of R*s/Rtot, Tc increased linearly with ln I(f). Within the linear range, the slope of the function yielded an apparent exponential time constant (tau c) of 1.7 +/- 0.2 s (mean +/- S.D.). Background light reduced the value of Tc measured at a given flash intensity but preserved a range over which Tc increased linearly with ln I(f); the linear-range slope was similar to that measured in the absence of background light. The intensity dependence of Tc resembles that of a delay (Td) seen in light-scattering experiments on bovine retinas, which describes the period of essentially complete activation of transducin following a bright flash; the slope of the function relating Td and ln flash intensity is thought to reflect the lifetime of photoactivated visual pigment (R*) (Pepperberg et al., 1988; Kahlert et al., 1990). The present data suggest that the electrophysiological delay has a similar basis in the deactivation kinetics of R*, and that tau c represents TR*, the lifetime of R* in the phototransduction process. The results furthermore suggest a preservation of the "dark-adapted" value of TR* within the investigated range of background intensity. PMID- 1739681 TI - American Society of Regional Anesthesia, annual meeting. Tampa, Florida, March 26 29, 1992. Abstracts. PMID- 1739682 TI - The vascular factor in low tension glaucoma: alchemists' gold? PMID- 1739683 TI - A primate model for age related macular drusen. AB - A closed colony of semi-free-ranging rhesus monkeys maintained in isolation since 1938 by the Caribbean Primate Research Center (CPRC) is being studied as a model for age related macular drusen. Of examined colony animals 57.7% of the monkeys and 47.3% of their eyes have drusen. The prevalence and severity of drusen are linearly related to increasing age and are significantly higher in specific maternal lineages (matrilines). An electrophysiological estimate indicates loss of function associated with drusen. Prevalence of drusen in CPRC females is almost twice that of males, while the prevalence among CPRC animals in general appears to be several times that of monkeys from continental US facilities. Evidence suggests that the frequency of endstage lesions is also similar to that in human populations. The CPRC matriline monkeys appear to provide the best model yet reported for human age related macular drusen. PMID- 1739684 TI - Surgically induced necrotising sclerokeratitis (SINS)--precipitating factors and response to treatment. AB - The clinical features, treatment, and visual outcome of 52 eyes from 43 patients who developed scleritis following surgery were reviewed. In all patients the scleral inflammation developed adjacent to a surgical wound. Ninety six per cent had necrotising disease and 23% also had evidence of secondary posterior scleritis. Many different types of ocular surgery were implicated and the majority (75%) of the patients had two or more surgical procedures before the onset of the scleritis. Although cataract extraction through a limbal incision resulted in the largest subgroup, scleritis also followed glaucoma, strabismus, and retinal detachment surgery. The latent period between surgery and the appearance of inflammation was short (mean 9 months) except for a small group in whom scleritis occurred many years after squint surgery. Sixty three per cent of patients had evidence of a systemic disease. Early diagnosis and aggressive medical treatment significantly improved the visual outcome. The precipitating factors, pathogenesis, and course of this condition are discussed. PMID- 1739685 TI - Finger blood flow in patients with low tension glaucoma and primary open-angle glaucoma. AB - Finger blood flow was studied by means of laser Doppler flowmetry in 12 patients with low tension glaucoma (LTG), 12 patients with primary open-angle glaucoma (POAG) and 12 normal subjects. Baseline flow, flow after immersion of the hand in warm water (+40 degrees C), and flow after exposure of the hand in cold water (+4 degrees C) were measured. Statistically significant differences were not found in each flow between the three groups of the patients (p greater than 0.05). Vasospastic response to warm and cold water was observed in 25% of LTG patients, 17% of POAG patients, and 25% of normal subjects. There was no significant difference between LTG, POAG, and normal subjects in finger blood flow. PMID- 1739686 TI - Is there a genetic basis for Fuchs' heterochromic uveitis? Discordance in monozygotic twins. AB - One pair, and probably two pairs, of monozygotic twins are reported with discordance for Fuchs' heterochromic uveitis (FHU). Regular Mendelian inheritance of this disease is now proved to be impossible. The heritability of FHU is low and may be zero. The possibility of any genetic predisposition to the disease and its association with 'simple' heterochromia are discussed. PMID- 1739687 TI - Autofluorescence of the crystalline lens in early and late onset diabetes. AB - Blue/green autofluorescence (excitation around 420 to 430 nm, emission around 520 nm) of the crystalline lens has been studied by an in vivo photographic method in two populations of diabetics and controls. The populations consisted of a geographically based survivor group of 161 mixed early and late onset diabetics (and 133 non-diabetic controls) and a second group of 104 early onset insulin dependent diabetics (and 138 non-diabetic controls), the latter all with non cataractous lenses. Powerful associations (p less than 10(-6) were found between the presence of diabetes and increased lenticular autofluorescence in both populations. Among the mixed diabetics diabetic type was a significant factor after accounting for the effects of age and diabetic duration. In the early onset group (clear lenses) a powerful association existed between autofluorescence and diabetic duration (p = 0.000011) after allowing for the effect of age, while in a subgroup of late onset diabetics with clear lenses this effect was modest (p = 0.015). In the early onset diabetic group diabetic retinopathy (p = 0.0064) was associated with increased lenticular autofluorescence after allowing for the effects of age and diabetic duration. In addition a powerful interaction between diabetic duration and the presence of diabetic retinopathy (p less than 10(-6) was found in this subgroup. Among the geographically based population of diabetics, increased nuclear brunescence was powerfully associated (p less than 10(-6) with increased autofluorescence after allowing for the effects of age, diabetic duration, and type of diabetes. This association was not found in the non-diabetic population. Non-enzymatic glycosylation of lens proteins should be considered as a possible mechanism of production of the fluorogen with emission around 520 nm. PMID- 1739688 TI - Modelling of changes in the corneal endothelium after cataract surgery and penetrating keratoplasty. AB - Long term changes in endothelial cell density were monitored in three groups of patients after surgery. One group underwent uncomplicated cataract surgery, one group complicated cataract surgery which eventually progressed to corneal decompensation, and one group penetrating keratoplasty. A mathematical model is presented which describes endothelial cell loss after surgery as an exponential decay process towards an asymptote with constant rate of cell loss over time. When fitted to the data from the three groups there is excellent agreement in each case. Discriminant analysis techniques were applied to model predictions to assess the likelihood of late corneal decompensation after surgery. From measurements of endothelial cell density before and after surgery we were able to correctly assign patients undergoing cataract surgery to decompensation or non decompensation groups in 85.7% and 92.7% of cases respectively. PMID- 1739689 TI - Survey of the contamination of eyedrops of hospital inpatients and recommendations for the changing of current practice in eyedrop dispensing. AB - Topical ophthalmic medications used on the ward and from the outpatient area have been taken and cultured for potential bacterial contamination in the laboratory. We examined 143 bottles used by patients who had had routine cataract surgery and trabeculectomy. We also examined for bacterial contamination 216 bottles of eyedrops used in the outpatient area of the hospital. No contamination was found in the postoperative eyedrops, but five bottles were contaminated from the outpatient area (2.3%). The bacterial growth from outpatient drops was of the same order of magnitude as in previous studies. The practice in the UK for postoperative eyedrops to be discarded and fresh, separate bottles to take home is discussed. We recommend that this practice be changed so that the postoperative drops used for 72 hours or less are taken home. PMID- 1739690 TI - Spontaneous congenital non-pigmented epithelial cysts of the iris stroma. AB - Histopathological and immunohistochemical findings in 11 patients with spontaneous congenital non-pigmented epithelial cysts of the iris stroma were studied. The cysts were lined by stratified squamous to unilayered cuboidal non pigmented epithelium. Goblet cells were present in nine cysts, indicating a similarity to conjunctival epithelium. The demonstration of higher-molecular weight keratins and absence of S-100 protein, by monoclonal and polyclonal antibodies, argues for surface ectodermal rather than neuroectodermal origin of the cysts. Theories of embryogenesis have been conflicting, but our results support the theory that they arise from surface ectoderm, displaced probably at the time of lens vesicle formation. The finding of normally sited subepithelial S 100 positive melanocytes may suggest that ectopic conjunctival epithelium can induce normal patterns of migration of neural crest cells. PMID- 1739691 TI - The optical spacer--a simple device which extends the scope of indirect ophthalmoscopy. AB - A simple device is described which both facilitates and significantly extends the scope of indirect ophthalmoscopy. PMID- 1739692 TI - Orbital lymphoproliferative disorders. PMID- 1739693 TI - Dedifferentiated chondrosarcoma arising in the orbit. AB - Orbital chondrosarcomas are extremely rare and are usually an extension of tumours involving the paranasal sinuses. A unique case of dedifferentiated chondrosarcoma arising solely within the orbit is presented. PMID- 1739694 TI - Periorbital necrobiosis lipoidica. AB - Necrobiosis lipoidica is a granulomatous skin condition typically occurring on the legs. A patient with this condition presented with gross bilateral induration of the eyelids sufficient to close both eyes. PMID- 1739695 TI - A clinicopathological study of ocular involvement in primary hyperoxaluria type I. AB - We performed a clinicopathological study on the eyes of a 3-year-old girl with primary hyperoxaluria type I. An examination one year before death disclosed a slightly diminished visual acuity in both eyes with black, geographic central macular, subretinal patches. Calcium oxalate was deposited predominantly in the retinal pigment epithelium of the posterior pole, where these cells were markedly hyperplastic and hypertrophied round foci of oxalate crystals. Oxalate crystals were exceedingly sparse in other ocular structures and when present were not associated with an apparent tissue reaction in these other locations. A collagenous layer was evident between parts of the retinal pigment epithelium and the neurosensory retina, which contained occasional perivascular clumps of melanin laden cells. The predominant deposition of oxalate in the retinal pigment epithelium, with the exuberant response of these cells around the crystals, gives a clue to the pathogenic mechanisms of primary hyperoxaluria. PMID- 1739696 TI - Vitelliform macular degeneration associated with mitochondrial myopathy. AB - A patient with mitochondrial myopathy is described. Examination of his fundus revealed bilateral vitelliform degeneration of the maculae. This lesion is a focal abnormality of the retinal pigment epithelium and may be a manifestation of the underlying mitochondrial disease. PMID- 1739697 TI - Penetrating keratoplasty for keratoconus. PMID- 1739698 TI - Trachoma still undefeated. PMID- 1739699 TI - Diabetic radiation morbidity. PMID- 1739700 TI - Hyperopic shift and the use of masking agents in excimer laser superficial keratectomy. PMID- 1739701 TI - Treatable blindness in temporal arteritis. PMID- 1739702 TI - Phenotypes of conjunctival inflammatory cells in sarcoidosis. AB - Phenotypes of the infiltrating mononuclear cells of the lower fornix conjunctiva of nine patients with sarcoidosis and six controls were studied using monoclonal antibodies and a modified immunoperoxidase method. Four patients had sarcoidosis of recent onset (duration of 2 years or less) and five patients had a chronic disease (duration of 3 or more years). The inflammatory cells in the sarcoid conjunctival specimens were predominantly T lymphocytes, the vast majority of which were of T helper/inducer subtype expressing Leu-3a + 3b positivity. The ratio of T helper/inducer cells to T suppressor/cytotoxic cells was 3.9 on average but only 0.9 in controls. Epithelioid cell granulomas were seen in three specimens in one case of recent onset and in two chronic cases comprising a marked amount (more than 15 cells/visual field) of cells bearing phenotypes of macrophages, T cells, T helper/inducer cells and HLA-DR antigen, and in smaller quantities of T suppressor/cytotoxic cells. The mean number of all immunocompetent cell subtypes of specimens from newly diagnosed patients exceeded that of specimens from chronic patients. We believe that the sarcoid immune reaction in the conjunctiva is a dynamic process in which proliferation of immunocompetent mononuclear cells precedes the stage of granuloma formation. PMID- 1739703 TI - Endothelin: a new vasoactive ocular peptide. PMID- 1739704 TI - Exudative retinal detachment and posterior scleritis associated with massive scleral thickening and calcification treated by scleral decompression. AB - A 66-year-old man presented with massive bilateral scleral thickening and calcification associated with a unilateral exudative retinal detachment which did not respond to systemic anti-inflammatory agents including steroids and cyclophosphamide but improved with scleral resection. This patient shows the features of both posterior scleritis and the uveal effusion syndrome, providing further evidence for the role of a thickened sclera and interference with the trans-scleral flow of fluid in the formation of such an exudative retinal detachment. PMID- 1739705 TI - Transient loss of peripheral vision as the presentation of left atrial myxoma. AB - A 42-year-old man developed transient loss of vision in both eyes. On echocardiography to investigate a systolic murmur and determine the potential source of emboli, a large left atrial myxoma was diagnosed. This was removed successfully leaving no visual or neurological deficit. PMID- 1739706 TI - Delleman syndrome: a case report and review. AB - A case of oculocerebrocutaneous syndrome is presented, to our knowledge the first to be reported in West Bank and Gaza. The child was of consanguinous parents. The clinical features of orbital cyst, periorbital cutaneous malformations, and cerebral malformations are described, together with a brief review of previous reports. The need for neurological follow-up of these cases is emphasised. PMID- 1739707 TI - Pituitary adenoma presenting as the Foster-Kennedy syndrome. AB - A 27-year-old man presented to the casualty department with visual failure. Clinically he demonstrated the Foster-Kennedy syndrome. Computed tomography revealed a large space-occupying lesion which was subsequently shown to be a pituitary adenoma. The literature is reviewed and possible mechanisms of the Foster-Kennedy syndrome are discussed. PMID- 1739708 TI - Premalignant melanosis of the conjunctiva and the cornea in xeroderma pigmentosum. AB - Xeroderma pigmentosum is a rare autosomal recessive dermatosis. The neoplastic changes in sunlight-exposed areas of the skin and eyes may be related to the impaired replication of ultraviolet radiation-damaged DNA. A 38-year-old Greek woman is reported with a mild form of xeroderma pigmentosum and primary acquired melanosis with atypia of her right limbal conjunctiva and cornea. The development of this precursor of conjunctival malignant melanoma in a xeroderma pigmentosum patient may support the putative role of sunlight exposure in malignant transformation of conjunctival melanocytes. PMID- 1739709 TI - Resection of intraocular squamous cell carcinoma. AB - A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva. PMID- 1739710 TI - Keratitis in Reiter's syndrome. PMID- 1739711 TI - Statistical standards. PMID- 1739712 TI - Amblyopia. PMID- 1739713 TI - Cataract surgery. PMID- 1739714 TI - Dominant cone dystrophy starting with blue cone involvement. PMID- 1739715 TI - Cause of blindness in the Central African Republic. PMID- 1739716 TI - Prospects for day-case vitreoretinal surgery. PMID- 1739717 TI - Cataracts in children with uveitis. PMID- 1739718 TI - Evaluation of outpatient experience with vitreoretinal surgery. AB - The experience of 55 consecutive individuals undergoing outpatient vitreoretinal surgery was evaluated. Objective variables, including preoperative and intraoperative information, subjective postoperative pain, and discomfort were measured with a previously validated 100 mm visual analogue scale. Patients also ranked the overall experience. Average pain and discomfort scores in the recovery room were 21.8 and 22.6 and overnight were 26.7 and 30.4 (scale 0 to 100), respectively. Eighty eight per cent of subjects were satisfied with the experience. Elevated pain and discomfort scores were statistically correlated with scleral buckling, prolonged surgical or recovery room time, requirement for parenteral pain medications, and high intraocular pressure on the first postoperative visit. None of the patients needed further hospital treatment. This study suggests that vitreoretinal surgery in an appropriately selected population does not require routine inpatient care. PMID- 1739719 TI - Lensectomy for complicated cataract in juvenile chronic iridocyclitis. AB - Experience with the removal of complicated cataract by lensectomy in patients with juvenile chronic iridocyclitis (JCI) has so far been limited. The results of lensectomy were reviewed retrospectively in 131 patients with JCI (187 eyes). The mean follow up period was 5 years 4 months. The main operative complication was accidental loss of lens material into the vitreous cavity. The postoperative complications were glaucoma (23 eyes, 15%), phthisis (14 eyes, 8%), secondary pupillary membranes (11 eyes, 6%), and retinal detachment (six eyes, 3%). The incidence of postoperative phthisis was related to the level of intraocular pressure (IOP) at the time of surgery. Twenty four per cent of hypotonous eyes and 4% of eyes with normal or elevated IOP became phthisical. Visual acuity was improved in 77%, was worse in 13%, and unchanged in 10% of eyes. The main causes of a postoperative visual acuity of 6/60 or less were glaucoma, amblyopia, and phthisis. Lensectomy did not appear to alter the course of uveitis. PMID- 1739720 TI - An experimental model of oculorespiratory reflex. AB - An experimental study of the oculorespiratory reflex (ORR) was conducted on 20 albino rabbits using a square wave (SW) type of stimulus. The ORR could be elicited in 100% of animals. The medial rectus was observed to be most reflexogenic for ORR. The frequency and pattern of ORR was not affected by bilateral vagotomy, intravenous atropine or glycopyrrolate, but could be completely abolished by retrobular block. PMID- 1739721 TI - Blood-ocular barrier permeability in monkeys. AB - The permeability of the blood-ocular barrier was investigated in five monkeys using vitreous fluorophotometry (VFP). Inward permeability (Pin) of the blood retinal barrier was calculated by a computer simulation method. Kinetic VFP was performed after intravitreal injection of fluorescein (F) or fluorescein monoglucuronide (FG). The estimated mean value of Pin (x10(-6) cm/min) was 4.8 (SD 1.2). The mean rates of loss (per hour) of F from the anterior chamber (Ka) and the vitreous (Kv) were 0.11 (SD 0.01) and 0.13 (SD 0.03), respectively, which were approximately three and four times greater than those of FG (0.04 (SD 0.01) and 0.03 (SD 0.01), respectively). Probenecid administered intraperitoneally decreased both the Ka and the Kv of F significantly but had no effect on the Ka or the Kv of FG, suggesting that F was excreted from the eye with the aid of the active transport mechanism. The results of comparative studies of the rates of loss of F from the anterior chamber (Ka) and from the vitreous (Kv) suggested that active transport was more predominant in the blood-retinal barrier than in the blood-aqueous barrier. PMID- 1739722 TI - A comparison of 141 polymacon (Iogel) and 140 poly(methyl methacrylate) intraocular lens implants. AB - In a prospective controlled trial 290 consecutive patients were randomly allocated a polymacon or a poly(methyl methacrylate) (PMMA) intraocular lens. Early Treatment of Diabetic Retinopathy Study (ETDRS) acuity charts gave similar results with both lenses. However Pelli-Robson contrast sensitivity charts gave a better result with PMMA lenses. Polymacon lenses appeared to remain free of any adhesions after implantation raising the question of long term stability. Four patients experienced problems related to this, three involved total lens dislocation. Seven patients developed early 'fibrin' membranes coating the polymacon lens, of which three were florid. PMID- 1739723 TI - Improved iodine-125 plaque design in the treatment of choroidal malignant melanoma. AB - The use and development of iodine-125 plaque therapy for choroidal malignant melanoma are described. Since 1975 experience has led to changes in plaque design and insertion techniques. Twenty-one patients were irradiated with local episcleral iodine-125 plaques. Three patients required a second plaque for tumour recurrence. Four eyes were enucleated because of continued tumour growth and a further eye was removed because of glaucoma secondary to radiation retinopathy. Two patients (9.5%) died of metastases. The remaining 19 patients are alive and clinically clear of metastases, with a mean follow up time of 73.1 months (range 43-142 months). PMID- 1739724 TI - Periocular migration of hard contact lenses. AB - Six cases are presented in which hard contact lenses have migrated into the periocular soft tissues, four into the eyelid, one into the orbit and one which spontaneously reappeared on the cornea 12 years after the patient had last worn contact lenses. Some possible mechanisms of this phenomenon and a review of the literature are presented. PMID- 1739725 TI - Occurrence of pseudoexfoliation following penetrating keratoplasty for keratoconus. AB - The occurrence of pseudoexfoliation (PSX) following penetrating keratoplasty for keratoconus is reported in three eyes of two patients. The patients' ages at keratoplasty were 37, 40, and 31 years, and PSX was first observed 5, 4, and 6 years following keratoplasty. The donor age was 76, 81, and 81 years. Possible explanations for the occurrence of PSX after keratoplasty include mere coincidence, some sort of non-specific reaction to surgery or to postoperative medication, an immunogenic reaction to transplanted foreign corneal tissue, and the hypothetical speculation that PSX might be a transmissible disease. PMID- 1739726 TI - Effects of NO2-modification of Tyr83 on the reactivity of spinach plastocyanin with cytochrome f. AB - We have investigated the electron transfer (ET) reactions between turnip cytochrome f, and the native and NO2-Tyr83-modified forms of spinach plastocyanin (PCu) at 10.0 degrees C and ionic strength 0.200 M(NaCl), in both directions as a function of pH. The PCu(II)/cytochrome f(II) rate constants in the pH-range 4-6.8 reflect active and remote binding site protonation. At higher pH, NO2-Tyr83 and positively charged residues on cytochrome f are deprotonated, and both native and NO2-modified PCu exhibit a composite rate constant variation in this pH range. When framed by ET theory this pattern is fully understandable in terms of variations in reduction potentials and electrostatic interactions, caused by the protonation equilibria. The rate constant ratio knitro/knative is, however, only 1.04 for the PCu(II)/cytochrome f(II) reactions in spite of a 18 mV higher reduction potential for NO2-Tyr83-modified PCu. This is much lower than the value of 1.42 expected from ET theory solely on the basis of such a reduction potential effect. A similar effect is seen for PCu(I)/cytochrome f(III) for which the low pH knitro/knative ratio is 0.51. Notable but smaller effects are also observed for the small reaction partners [Fe(CN)6]3-/4- and [Co(phen)3]3+/2+. The effect of NO2-modification in addition to the reduction potential effect can be resolved into a small reorganization energy increase around the copper atom and a smaller electronic transmission coefficient for ET through the Cu/Cys84/Tyr83 sequence. The former effect dominates in the reactions with the small reaction partners, while the electronic effects contribute significantly for PCu/cytochrome f, supporting the concept that the PCu/cytochrome f ET is at the remote PCu binding site. PMID- 1739727 TI - Differential permeability for lipophilic compounds in uncoupler-resistant cells of Escherichia coli. AB - The acrA strain AS-1 of Escherichia coli is more sensitive than its parent W3110 to growth inhibition by Methylene blue, sodium dodecyl sulfate and novobiocin. UR 3 is an uncoupler-resistant strain isolated from AS-1 which is resistant to growth inhibition by carbonylcyanide m-chlorophenylhydrazone (CCCP), 3,3',4',5 tetrachlorsalicylanilide (TCS) and tributyltin chloride, while remaining sensitive to the first group of compounds. A revertant of AS-1 acquired resistance to Methylene blue and sodium dodecyl sulfate but remained sensitive to uncouplers. In contrast to AS-1, proline uptake in UR-3 was resistant to uncouplers. Strain UR-3 grown in the presence of uncoupler incorporated elongation factor Tu to high levels in the outer membrane of the cell. A role for the outer membrane in the acquisition of uncoupler-resistance by UR-3 is suggested by the behaviour of the mutant to the fluorescence probe N-phenyl-1 naphthylamine. The fluorescence intensity of this probe was quenched by membrane energization in the wild-type strain W3110 but not in AS-1. UR-3 behaved like W3110, suggesting that an outer membrane barrier to neutral lipophilic compounds like N-phenyl-1-naphthylamine (NPN) and uncouplers had been restored in UR-3. By contrast, AS-1 and UR-3 both allowed energized uptake of the fluorescent lipophilic cation 2-(dimethylaminostyryl)-1-ethylpyridinium (DMP+). It is concluded that lipophilic materials must permeate the outer membrane of E. coli by at least two different routes. However, uncoupler-resistance in UR-3 appears to be more complex than the provision of an outer membrane barrier to uncouplers. Thus, uncouplers readily discharged a pH gradient established in both AS-1 and UR 3 by addition of HCl to cell suspensions. PMID- 1739728 TI - Mechanism of energization of uptake of the fluorescent dye 2-(4 dimethylaminostyryl)-1-ethylpyridinium cation [DMP+] into an acrA strain of Escherichia coli. AB - The mechanism of uptake of the fluorescent dye 2-(4-dimethylaminostyryl)-1 ethylpyridinium cation (DMP+) into cells and vesicles of the acrA strain AS-1 of Escherichia coli was examined. Uptake was energized by substrate oxidation and discharged by uncouplers. Uptake was enhanced by the presence of tetraphenylphosphonium cation, tetraphenylboron anion and tributyltin chloride, which may inhibit the efflux system for DMP+. Uptake was inhibited by 5 methoxyindole-2-carboxylic acid (MIC). By the use of ionophores with right-side out vesicles loaded with monovalent cations it was shown that DMP+ uptake could be driven both by the establishment of a membrane potential across the vesicle membrane and by a H+/DMP+ antiport system. Attempts to demonstrate the latter mechanism in everted membrane vesicles were unsuccessful. PMID- 1739729 TI - The fluorescence yield of Rhodopseudomonas viridis in relation to the redox state of the primary electron donor. AB - The fluorescence yield of bacteriochlorophyll (BChl) b in membranes of Rhodopseudomonas viridis was measured immediately and at a variable time-interval after a saturating laser flash to bring about charge separation. At 4 K a decrease of the yield by 28% was observed immediately after the flash. This yield recovered mono-exponentially with a time constant of 6.3 +/- 0.4 ms to approximately the original level. The same time constant was observed for the re reduction of the primary electron donor, indicating that the fluorescence quenching can be ascribed to the oxidation of the primary donor. The extent of quenching decreased with increasing temperature and reversed to a fluorescence increase at temperatures above 50 K. These results may be explained by the presence of long-wavelength absorbing BChls b in the antenna which at low temperature transfer their excitation energy more efficiently to the oxidized than to the reduced primary donor, in support of a similar hypothesis used to explain the quenching of fluorescence by 'oxidized' reaction centers in heliobacterium chlorum (Deinum, G., Kramer, H., Aartsma, T.J. Kleinherenbrink, F.A.M. and Amesz, J. (1991) Biochim. Biophys. Acta 1058, 339-344). PMID- 1739730 TI - Characterisation of photoinduced breakdown of the D1-polypeptide in isolated reaction centres of Photosystem II. AB - When the isolated reaction centre of Photosystem II, reconstituted with the quinone, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), is exposed to photoinhibitory illumination, a D1-polypeptide breakdown product of 24 kDa is detected by immunoblotting. In addition, weaker bands are also detected at 17, 13 and 10 kDa. It is suggested that the 24 kDa D1-polypeptide breakdown product is the same as that first observed in vivo by Greenberg et al. (1987) EMBO J. 6, 2865-2869. Its appearance in isolated Photosystem II reaction centres requires the presence of an electron acceptor, but occurs under both aerobic and anaerobic conditions. In our in vitro experimental system the photoinduced degradation of the D1-polypeptide to the 24 kDa fragment was related to the functional activity of the reaction centre and the enzymatic nature of the proteolysis was characterised by a pH optimum of about 8.0 and by inhibition with proteinase inhibitors, especially the serine-type soybean trypsin inhibitor. The results support our earlier findings (Shipton and Barber (1991) Proc. Natl. Acad. Sci. USA 88, 6691-6695) that the appearance of the light-induced D1-polypeptide breakdown pattern of fragments occurs as a consequence of donor side photoinhibition when highly oxidising species accumulate in the reaction centre and bring about pigment oxidation and degradation. We suggest that it is this selective loss of pigments that induces a conformational change in the D1 polypeptide which triggers its autoproteolytic cleavage. PMID- 1739731 TI - Mediation of glycosylated and partially-deglycosylated glucose oxidase of Aspergillus niger by a ferrocene-derivatised detergent. AB - A ferrocene-derivatised detergent, (11-ferrocenylundecyl) trimethylammonium bromide (FTMAB), when oxidised to the corresponding ferricinium ion, was found by electrochemical studies to be an effective electron acceptor for reduced glucose oxidase of Aspergillus niger (EC 1.13.4) and thus acts as a electron-transfer mediator between glucose oxidase and a working electrode held at a potential sufficiently positive to reoxidise reduced FTMAB. An increase in mediating activity was produced when FTMAB was present in concentrations above its critical micelle concentration. An 'enzyme electrode' was formed by adsorption of glucose oxidase and FTMAB surfactant on a graphite rod. The electrode functioned as an amperometric biosensor for glucose in phosphate-buffered saline solution. A mixed micelle of glucose oxidase and FTMAB, probably adsorbed on the electrode surface, appears to be advantageous for the amperometric determination of glucose. Additionally, glucose oxidase was treated with alpha-mannosidase. When this partially-deglycosylated glucose oxidase was incorporated in an enzyme electrode, a 100-fold increase in the second-order rate constant (k) for electron transfer between the enzyme and FTMAB was observed, together with increased current densities, with respect to the equivalent values for FTMAB and commercial glucose oxidase. The use of deglycosylated enzymes in biosensors is suggested. PMID- 1739732 TI - Beta-alanine transaminase activity in black and suppressor of black mutations of Drosophila melanogaster. AB - An assay for beta-alanine transaminase activity in extracts of Drosophila melanogaster has been developed. By use of this assay, the levels of beta-alanine transaminase activity in several strains of flies has been examined as a function of developmental age. The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type. PMID- 1739733 TI - Effect of oxygen tension and lactate concentration on keratan sulphate and chondroitin sulphate biosynthesis in bovine cornea. AB - Calf cornea slices were incubated with [U-14C]glucose, in varying pO2 or lactate concentrations. Acid glycosaminoglycans were separated by ion-exchange chromatography after papain digestion. The percentage radioactivity incorporated into keratan sulphate increased markedly with decreased oxygen tension, whereas a concomitant relative decrease of the biosynthesis of glycosaminoglycuronans occurred. Similar results were obtained with increased lactate concentration. Our findings support the idea that keratan sulphate is a functional substitute for chondroitin sulphate in conditions of oxygen lack (Scott, J.E. and Haigh, M. (1988) J. Anat. 158, 95-108). PMID- 1739734 TI - Photosensitization of aqueous model systems by hypericin. AB - Absorption and fluorescence measurements of purified hypericin (HY) were made in various media. Photosensitization of two aqueous systems was investigated: resealed red blood cell membranes (ghosts) and hen lysozyme (Lys). Solubilization of HY by ghost membranes was shown by means of diffuse reflectance spectroscopy. Visible light irradiation of the ghosts incorporating HY led to lipid peroxidation with evidence of singlet oxygen involvement. A binding model applicable for insoluble ligands is indicative of strong HY binding to HSA. The HY-HSA complex photosensitized inactivation of Lys. The pseudo-first-order reaction kinetics with protection by azide ion are consistent with a Type II mechanism mediated by singlet oxygen. The results are discussed in the context of the HY photodynamic and antiretroviral activities. PMID- 1739735 TI - Influence of glucogenic amino acids on the hepatic metabolism of threonine. AB - The supplementation of a low-protein diet with L-threonine leads to a marked accumulation of threonine in plasma and liver, whereas increasing dietary protein generally leads to an induction of threonine dehydratase in the liver, hence depressed availability for extrasplanchnic tissues. The aim of the present study was, thus, to further investigate the factors which control the utilization of threonine by the liver. Increasing the dietary supply of threonine led to parallel increases in the afferent and hepatic concentrations and in the rate of utilization by the liver; however, the fractional extraction tended to decrease. It appears that the addition of a mixture of glucogenic amino acids to the diet prevented the accumulation of threonine in plasma induced by exogenous threonine. The glucogenic amino acids increased the fractional hepatic uptake of threonine, and counteracted its accumulation in the liver. These effects reflect the fact that the glucogenic amino acids elicited a potent induction of the threonine dehydratase, whereas threonine alone was uneffective. Our results suggest that, besides the well-established effect of glucogenic conditions, the availability of some glucogenic amino acids is an important factor in the control of threonine catabolism. PMID- 1739736 TI - N3-haloacetyl derivatives of L-2,3-diaminopropanoic acid: novel inactivators of glucosamine-6-phosphate synthase. AB - N3-Haloacetyl derivatives of L-2,3-diaminopropanoic acid, novel glutamine analogs, were shown to be strong inhibitors of glucosamine-6-phosphate synthase from bacteria and Candida albicans. The inhibition was competitive with respect to glutamine and non-competitive with respect to D-fructose-6-phosphate. In the absence of glutamine, the tested compounds inactivated glucosamine-6-phosphate synthase from C. albicans with Kinact = 0.5 microM, 0.55 microM and 18.5 microM for bromoacetyl-, iodoacetyl- and chloroacetyl derivatives of L-2,3 diaminopropanoic acid, respectively. The inactivation obeyed the criteria for active site-directed modification. PMID- 1739737 TI - In vivo insulin responsiveness for glucose uptake and production at eu- and hyperglycemic levels in normal and diabetic rats. AB - Whole body glucose uptake (BGU) and hepatic glucose production (HGP) at maximal plasma insulin concentrations (+/- 5000 microU/ml) were determined by eu- (EC) (6 mM) and hyperglycemic (HC) (20 mM) clamps (120 min), combined with [3-3H]glucose infusion, in normal and streptozotocin-treated (65 mg/kg) 3-day diabetic, conscious rats. In normal rats, during EC, BGU was 12.4 +/- 0.4 mg/min and during HC, when urinary glucose loss was 0.54 +/- 0.09 mg/min, BGU was 25.5 +/- 1.6 mg/min. However, throughout the final 60 min of HC, glucose infusion rate (GIR) was not constant but a linear decline in time (r = -0.99) of 17%, P less than 0.0001, was observed indicating a hyperglycemia-induced desensitization process. In diabetic rats, during EC, BGU was 7.7 +/- 0.3 mg/min and during HC, BGU was 15.5 +/- 1.4 mg/min. Throughout the final 60 min of HC, GIR was constant, suggesting that the hyperglycemia-induced desensitization process was already completed. In normal and diabetic rats, HGP was similar: during EC 0.2 +/- 0.5 mg/min and 0.1 +/- 0.5 mg/min, and during HC 0.4 +/- 0.4 mg/min and 0.5 +/- 0.6 mg/min, respectively. In vitro adipocyte and muscle insulin receptor studies showed normal to increased receptor number and increased receptor autophosphorylation in diabetic compared to normal rats. IN CONCLUSION: (i) 3-day diabetic rats show, at maximal plasma insulin concentrations, insulin resistance to BGU, but not to HGP. The resistance to BGU is equally present (reduction of 38%) at eu- and hyperglycemic levels as compared to normal rats. (ii) 3-day diabetic rats reveal no defect in adipocyte and muscle insulin receptor function. These data indicate that the diabetes induced insulin resistance for BGU is at the post-receptor level and due to a decreased maximal capacity (Vmax) for glucose uptake, with no change in affinity, or Km. PMID- 1739738 TI - Parallel stranded DNA under the scanning tunnelling microscope. AB - Using scanning tunnelling microscopy, we have directly observed parallel stranded DNA helixes of 43 nucleotides in length. The double helix is right-handed and has an average spacing, 17.43 A (+/- 1 S.D.: 2.30 A), and an average apparent depth, 4.79 A (+/- 1 S.D.: 1.04 A) for each groove. The average pitch of the helical turn is 34 A (+/- 1 S.D.: 3.35 A) and consists of no more than ten base pairs. The diameter of the helix is approx. 17-20 A. Our results provide direct evidence for the existence of a parallel structure of DNA in vitro and some details of its fine structure. PMID- 1739739 TI - Differential and coordinate responses of the human genes encoding the heat stable alkaline phosphatases to cAMP and sodium butyrate in the choriocarcinoma line JEG 3. AB - Human heat stable alkaline phosphatases are encoded by two closely related genes: the PLAP-1, which specifies the term placental enzyme, and the PLAP-2, which is expressed primarily in germ cells. In the choriocarcioma line JEG-3, 8-Br-cAMP induced the accumulation of the mRNA of both genes, while sodium butyrate induced the accumulation of PLAP-2 transcripts only. Each agent increased the transcription rate of one or both of the genes, as assayed by run-on transcription. In transfection of JEG-3 cells with PLAP promoters fused to the firefly luciferase gene, the activity of the PLAP-2 promoter (but not PLAP-1) was induced with sodium butyrate, while both promoters were induced by 8-Br-cAMP. Inducibility of the PLAP-2 promoter by 8-Br-cAMP was still observed when the promoter was shortened to -103, leaving intact a sequence resembling a cAMP response element. The extent of transcriptional activation by either agent was not sufficient to explain the accumulation of PLAP mRNA. These studies suggest that both transcriptional and posttranscriptional processes are involved in the induction of the PLAP-1 and PLAP-2 gene in JEG-3 cells. PMID- 1739740 TI - TRH-related peptides in the rabbit prostate complex during development. AB - The novel peptide, pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2), has recently been isolated and characterized from the rabbit prostate complex. The tripeptide is present in high concentrations in the prostate complex and semen, together with a 40-50 residue polypeptide which contains a TRH-immunoreactive fragment at its C-terminus. The present study investigates changes in the levels of these TRH-related peptides in rabbits aged 11 weeks, 4 months, 7 months, 13 months and 2 years. For each age group the peptides were extracted from the prostate complex, separated by gel exclusion chromatography, and located by TRH radioimmunoassay. The TRH-immunoreactive fragment was released from the polypeptide by trypsin digestion prior to radioimmunoassay. Very low concentrations of TRH-immunoreactive peptides were present at 11 weeks of age, but considerable levels of both peptides were found in all the other age groups. Anion exchange chromatography, under conditions which resolve TRH and pGlu-Glu ProNH2, showed that the majority of the low molecular weight TRH immunoreactivity co-eluted with synthetic pGlu-Glu-ProNH2. The remaining TRH immunoreactivity, which had not bound to the anion resin, also failed to bind to a cation exchange column at pH 2.0, indicating that it was not authentic TRH. Dissection of the prostate complex into its four constitutive regions (vesicular gland, coagulating gland, prostate and bulbourethral gland) followed by extraction, chromatography and TRH radioimmunoassay of each region showed that the TRH-related peptides were located in the prostate. PMID- 1739741 TI - Identification of superoxide dismutase in rat liver peroxisomes. AB - In this paper we have investigated whether or not superoxide dismutase is localized in peroxisomes from rat liver. Using an improved method to prepare peroxisomes from clofibrate induced rat livers, we identified superoxide dismutase activity in peroxisomes. This activity was found to be predominantly of the copper-zinc type. The finding of superoxide dismutase activity in peroxisomes makes sense since peroxisomes also contain superoxide generating enzyme activities such as xanthine oxidase. PMID- 1739742 TI - Insect glycolipids. AB - Systematic elucidations of the chemical structures of glycosphingolipids from members of the phyla Arthropoda (class:insecta) of the Protostomia have shown several characteristic differences to those of the Deuterostomia, e.g., the Vertebrata. The ceramide constituents of the arthropod sphingolipids are C14:1- and C16:1-sphingoid and a majority of saturated C18-, C20-, C22- and C24-fatty acids. The GSL of the dipteran insects, L. caesar and C. vicina, consist of a series of homologous compounds of increasing sugar chain length. The carbohydrate moieties of these arthropod GSL are all derived from one unique neutral sugar core sequence, the arthro-series. The longest member known, an arthrononaosylceramide has the structure Gal beta,3GalNAc beta,3GlcNAc beta,3Gal beta,3GalNAc alpha,4GalNAc beta,4GlcNAc beta,3Man beta,4Glc beta Cer. Three pentahexosylceramides have been characterized that differ in their nonreducing terminus, i.e., IV4GalNAc alpha-Ap4Cer, IV3Gal alpha-Ap4Cer and IV3Gal beta Ap4Cer. A large repertoire of structural variations of the arthro-series GSL is created by two types of derivatisations of the neutral carbohydrate core: addition of a zwitterionic 2-aminoethylphosphate group in phosphodiester linkage to the 6-position of the III-N-acetylglucosamine of the arthrotriaosylceramide core and/or substitution of a terminal galactose in 3-position by a glucuronic acid residue. The latter acidic arthro-series GSL were given the name arthrosides. Preliminary results have indicated that the blowfly GSL component distribution is strongly organ specific. GSL of various larval organs are distinguished by the length of their neutral core carbohydrate chain, as well as, the degree of PEtn- and GlcA-substitutions. Normal human sera contain antibodies that recognize epitopes on arthro-series GSL. Thereby, sites of the neutral carbohydrate chain, as well as, the zwitterionic and acidic epitopes are involved in the immune recognition. In a pathological condition, a M-protein of patients with autoallergic demyelinating peripheral neuropathy was found to react strongly with a glucuronic acid-containing molecular structure on arthrosides. Some indication was obtained for a possible functional role of glucuronic acid in dipteran-cell adhesion by using a mouse monoclonal antibody, mAb CAF-I. This antibody, directed against an arthroside epitope involving glucuronic acid, could induce an in vitro detachment of insect cells from one another or from their substratum. Obviously, present research on the GSL of insects is only at an early stage. Nevertheless, from the results available so far it was become increasingly apparent that a new chapter in our knowledge of GSL structures has been opened.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1739743 TI - A defect in the sterol:steryl ester interconversion in a mutant of the yeast, Saccharomyces cerevisiae. AB - A culture cycle dependent interconversion of sterols and steryl esters is disturbed in a mutant of Saccharomyces cerevisiae. Independent extragenic suppressors to this mutant return the mutant's pleiotropic phenotype to that of the parental wild type. Concomitant with the alterations in interconversion, modifications were found in the yeast proteins that antigenically react with antibodies elicited against mammalian apolipoproteins. Suppressor mutations returned the aberrant immunoblot banding pattern of the mutant to that of the wild type in apolipoprotein B. PMID- 1739744 TI - Hepatic and nonhepatic sterol synthesis and tissue distribution following administration of a liver selective HMG-CoA reductase inhibitor, CI-981: comparison with selected HMG-CoA reductase inhibitors. AB - Since cholesterol biosynthesis is an integral part of cellular metabolism, several HMG-CoA reductase inhibitors were systematically analyzed in in vitro, ex vivo and in vivo sterol synthesis assays using [14C]acetate incorporation into digitonin precipitable sterols as a marker of cholesterol synthesis. Tissue distribution of radiolabeled CI-981 and lovastatin was also performed. In vitro, CI-981 and PD134967-15 were equipotent in liver, spleen, testis and adrenal, lovastatin was more potent in extrahepatic tissues than liver and BMY21950, pravastatin and PD135023-15 were more potent in liver than peripheral tissues. In ex vivo assays, all inhibitors except lovastatin preferentially inhibited liver sterol synthesis; however, pravastatin and BMY22089 were strikingly less potent in the liver. CI-981 inhibited sterol synthesis in vivo in the liver, spleen and adrenal while not affecting the testis, kidney, muscle and brain. Lovastatin inhibited sterol synthesis to a greater extent than CI-981 in the spleen, adrenal and kidney while pravastatin and BMY22089 primarily affected liver and kidney. The tissue distribution of radiolabeled CI-981 and lovastatin support the changes observed in tissue sterol synthesis. Thus, we conclude that a spectrum of liver selective HMG-CoA reductase inhibitors exist and that categorizing agents as liver selective is highly dependent upon method of analysis. PMID- 1739745 TI - Plasma lipid transport in the preruminant calf, Bos spp: primary structure of bovine apolipoprotein A-I. AB - The preruminant calf (Bos spp.) is a model of considerable interest with regard to hepatic and intestinal lipoprotein metabolism (Bauchart et al., J. Lipid Res. (1989) 30, 1499-1514 and Laplaud et al., J. Lipid Res. (1990) 31, 1781-1792). As a preliminary step towards future experiments dealing with HDL metabolism in the calf, we have purified apoA-I from this animal and determined its complete amino acid sequence. Thus, approx. 10% of calf apoA-I was shown to contain a propeptide, with the sequence Arg-His-Phe-Trp-Gln-Gln. Enzymatic cleavage of apoA I resulted in 10 proteolytic peptides. The complete apoA-I sequence was obtained after alignment of peptides on the basis of their homologies with those from rabbit apoA-I. Thus calf apoA-I consists of 241 amino acid residues, and exhibits high sequence homology with all mammalian apoA-I's studied to date. The bovine protein contained 10 hydrophobic amphipathic helical regions, occurring between residues 43-64, 65-86, 87-97, 98-119, 120-141, 142-163, 164-184, 185-206, 207-217 and 218-241. A computer-constructed phylogenetic tree showed that bovine apoA-I was more closely related to its dog counterpart, including the presence of a single methionine, than to the corresponding macaque and human proteins. Comparative predictions of the respective antigenic structures of human and bovine apoA-I's using the Hopp-Woods algorithm indicated similar positions for all 13 detectable antigenic sites, among which 7 were of identical, or closely related, amino acid composition. This finding was confirmed by demonstration of partial immunological identity between the two proteins upon immunodiffusion analysis, a result obtained using a monospecific rabbit antiserum against bovine apoA-I. Finally, comparison of sequence homology between bovine apoA-I and the lecithin:cholesterol acyl transferase (LCAT) activating region of human apoC-I suggests that several LCAT activating domains may be present in calf apoA-I. PMID- 1739746 TI - Effect of beta-lactoglobulin on the activity of pregastric lipase. A possible role for this protein in ruminant milk. AB - The interaction of bovine beta-lactoglobulin with palmitic and oleic acids has been studied by a partition equilibrium method. Bovine beta-lactoglobulin displays only one high affinity binding site for fatty acids whose association constants for palmitic and oleic acids are 4.2 x 10(6) and 2.3 x 10(6) M-1, respectively. However, other binding sites with low affinity are also present. The existence of one high affinity binding site is in accordance with the amount of fatty acids naturally bound to beta-lactoglobulin isolated from milk. The effect of beta-lactoglobulin on ruminant pregastric lipases from a pharyngeal extract has been assayed. The activity of pharyngeal lipase on a triglyceride emulsion is increased about 200%, 250% and 190% in the presence of 10 mg/ml, 20 mg/ml and 40 mg/ml of beta-lactoglobulin, respectively, the last concentration representing that found physiologically in colostrum. Albumin, another ligand binding protein, increases the activity of this enzyme to a lesser extent and high levels tend to inhibit enzyme action. These results indicate that beta lactoglobulin could participate in the digestion of milk lipids during the neonatal period by enhancing the activity of pregastric lipase through removal of the fatty acids that inhibit this enzyme. PMID- 1739747 TI - Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases. AB - A cytochrome P-450 (P-450), designated P-450HK omega, has been isolated and purified from human kidney microsomes to a specific content of 13 nmoles of P 450/mg of protein. P-450HK omega showed an apparent molecular weight of 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Absolute spectra of the oxidized form indicated that this P-450 was largely in the low spin state and partly in the high-spin state. It catalyzed the omega- and (omega 1)-hydroxylation of fatty acids such as laurate, myristate, and palmitate, with no activity toward prostaglandin A1, benzphetamine, 7-ethoxycoumarin, or 7 ethoxyresorufin. The first 35 NH2-terminal amino acid sequence of P-450HK omega had about 70% homology with those of rabbit kidney fatty acid omega-hydroxylases of the P-450 IVA gene subfamily, P-450ka-1, P-450ka-2, and P-450kd, except for four undetermined residues. Moreover, Western blot and immuno-inhibition studies showed that P-450HK omega reacted with an antibody against the rabbit kidney fatty acid omega-hydroxylase. The results suggest that P-450HK omega is a member of the same P-450 gene family (IVA subfamily) as the rabbit enzymes. In addition, the terminal sequence of P-450HK omega also showed 54% homology with that of P 450k-2, a fatty acid omega-hydroxylase from rat kidney microsomes. To our knowledge, this is the first time that a P-450 specific for fatty acid omega hydroxylase activity has been isolated to homogeneity from human tissues. PMID- 1739748 TI - Effects of clofibrate feeding on essential fatty acid desaturation and oxidation in isolated rat liver cells. AB - The effects of clofibrate feeding on the metabolism of polyunsaturated fatty acids were studied in isolated rat hepatocytes. Administration of clofibrate stimulated the oxidation and particularly the peroxisomal beta-oxidation of all the fatty acids used. The increase in oxidation products was markedly higher when n-3 fatty acids were used as substrate, indicating that peroxisomes contribute more to the oxidation of n-3 than n-6 fatty acids. The whole increase in oxidation could be accounted for by a corresponding decrease in acylation in triacylglycerol while the esterification in phospholipids remained unchanged. A marked stimulation of the amounts of newly synthesized C16 and C18 fatty acids recovered, was observed when 18:2(n-6), 20:3(n-6), 18:3 (n-3) and 20:5(n-3), but not when 20:4(n-6) and 22:4(n-6) were used as substrate. This agrees with the view that extra-mitochondrial acetyl-CoA produced from peroxisomal beta-oxidation is more easily used for fatty acid new synthesis than acetyl-CoA from mitochondrial beta-oxidation. The delta 6 and delta 5 desaturase activities were distinctly higher in cells from clofibrate fed rats indicating a stimulating effect. PMID- 1739749 TI - UV-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. 4. Calcium is involved in the cytotoxicity of UV-treated LDL on lymphoid cell lines. AB - In lymphoid cells pulsed with 'cytotoxic' concentrations of UV-treated LDL, the study of the variations of free cytosolic calcium concentration, of the influence of extracellular calcium and of the protective effect of calcium chelators suggests that both intra- and extracellular calcium could play a major role in the genesis of cell injury leading to cell death. (1) A dramatic sustained rise of cytosolic free calcium (the level of free cytosolic calcium was higher than 500 nmol/l for 6 h or more) occurred several hours after the beginning of the pulse with UV-treated LDL (lag period between 6 and 12 h). (2) The rise of the free cytosolic calcium and the 'cytotoxicity' induced by UV-treated LDL were largely dependent on the concentration of extracellular calcium which has an effect on the uptake of UV-treated LDL and on the expression of the 'cytotoxicity' at the cellular level. (3) The study of the sequence of intracellular events showed that the cellular oxidative stress generated by oxidized LDL was followed by the rise of free cytosolic calcium and later by the rise of 'cytotoxicity' indexes. (4) The intracellular calcium chelators, BAPTA/AM and EGTA/AM, were able to partially protect lymphoid cells against the 'cytotoxicity' of oxidized LDL. The supposed mechanisms of the free cytosolic calcium rise and the respective role of calcium or/and other factors (for instance direct lesions of the plasma membrane by the oxidative stress due to oxidized LDL) in the genesis of cellular lesions leading to cell death are discussed. PMID- 1739750 TI - Inhibition of prostaglandin synthesis in human endothelial cells treated with metabolic inhibitors. AB - Endothelial cell injury is often associated with increased synthesis of prostaglandin (PG)I2. We observed, however, that endothelial cells treated with metabolic inhibitors which reduce cellular ATP content develop an injury pattern characterized by reduced PGI2 synthesis. This study examined the relationship between cell injury, arachidonic acid metabolism and ATP content in human umbilical vein endothelial cells treated with 2-deoxyglucose (2DG), a glycolytic inhibitor, and oligomycin (OG), a respiratory chain inhibitor. Either inhibitor alone significantly reduced cellular ATP concentrations, but only OG reduced basal PG synthesis. The combination of 2DG and OG, however, was more effective than either agent alone in reducing cellular ATP content (greater than or equal to 50% of control) and inhibiting basal and agonist-stimulated PGI2 synthesis. This reduced PGI2 synthesis preceded 51chromium release, lactic dehydrogenase release and was not associated with a net release of arachidonic acid from cell membranes. Histamine, A23187 and bradykinin stimulated PGI2 synthesis in untreated but not in 2DG and OG treated cells. Exogenous arachidonic acid increased PGI2 synthesis to a similar extent in both 2DG and OG treated and untreated cells. Therefore, reduced PG synthesis in 2DG and OG treated endothelial cells is not due to inhibition of cyclooxygenase. Furthermore, reduced PG synthesis in these cells occurs prior to cell injury and is not strictly associated with cellular ATP depletion. PMID- 1739751 TI - Down-regulation of hepatic lipase gene expression and activity by fenofibrate. AB - The influence of the hypolipidemic drug, fenofibrate, on hepatic lipase (HL) gene expression and activity was investigated in the rat. Fenofibrate treatment provoked a dose-dependent decrease in HL mRNA levels. At a dose of 0.5% (w/w), HL mRNA levels were reduced to nearly 50% the levels in untreated controls. This decrease was parallelled by a comparable reduction in liver HL activity. The decrease in HL mRNA levels was already observed after 1 day of fenofibrate treatment. Whole liver perfusion experiments showed that the heparin-releasable HL activity in fenofibrate-treated livers dropped to 10% the activity in control livers. In conclusion, treatment with fenofibrate decreases HL gene expression, leading to a lowered activity of endothelium bound HL in fenofibrate-treated livers. PMID- 1739752 TI - 36th annual meeting of the GTH (German Thrombosis and Hematology Society). Heidelberg, 9-12 February 1992. Abstracts. PMID- 1739753 TI - Sensitivity of CFU-E to exogenous erythropoietin in benzene-treated mice. AB - Normal as well as hypertransfused BDF1 mice were exposed to 300 ppm of benzene, 6 h/day, 5 days per week for 2, 4, and 6 weeks respectively. Erythroid-committed hematopoietic progenitor cells CFU-E were determined in the bone marrow, and 59Fe incorporation was measured in the peripheral blood 48 h after its injection, as an indicator of active erythroid cell production. CFU-E numbers were reduced in benzene-exposed mice at all intervals, as was 59Fe incorporation in the peripheral blood after 2 weeks of exposure. In hypertransfused mice the CFU-E suppression, caused primarily by the hypertransfusion, was aggravated by benzene. After injection of 1 IU Ep 4 days before killing the CFU-E numbers and the 59Fe incorporation increased in controls as well as in benzene-exposed animals, but the difference persisted. After nine consecutive Ep injections the difference concerning the femur disappeared after 2 and 6 weeks of benzene exposure but was still present in the peripheral blood. These results suggest that chronic benzene exposure has a negative effect on early erythroid-committed, Ep-responsive hematopoietic cells. PMID- 1739754 TI - Recombinant human erythropoietin for the treatment of anemia in the myelodysplastic syndromes: a clinical and erythrokinetic assessment. AB - The clinical and ferrokinetic effects of escalating doses of subcutaneously administered recombinant human erythropoietin (rh-EPO) were studied in ten patients with myelodysplastic syndromes and severe transfusion-dependent anemia. Red blood cell transfusion requirements diminished in four patients, and one of the patients eventually became transfusion independent with an EPO-induced rise of Hb from 7.7 g/dl to 12.3 g/dl. Endogenous serum levels of EPO were significantly increased in all patients (100-5700 mU/ml), but three of four responders had a relatively low baseline level. The effective red cell iron turnover (RCIT) improved in two responding patients and even normalized in one patient. This increase in RCIT was accompanied with a decline in the ineffective red cell iron turnover (IIT). The other responding patients had a relatively preserved RCIT before EPO treatment. EPO therapy further increased the fraction of IIT in the latter patients. Red cell survival time did not increase during EPO therapy, even in the responding patients. One transient and one maintained increase in platelet count were observed. Disease progression with a sustained increase in blast cells in one patient and a transient elevation of blasts in another patient was seen. No other side effects of EPO therapy were observed. These results suggest that anemic MDS patients with low serum EPO levels and relatively spared effective erythropoiesis as measured by ferrokinetic studies may be the best candidates for treatment with recombinant human EPO. PMID- 1739755 TI - The contribution of DNA analysis to carrier detection and prenatal diagnosis of hemophilia A and B. AB - Developments in DNA technology have provided a novel means of carrier detection and prenatal diagnosis of hemophilia A and B. The collection of a large set of data has enabled us to evaluate the present feasibility and reliability of a diagnosis at the gene level and its contribution to methods already available. Since 1984, 533 potential and obligate carriers belonging to 170 families with hemophilia have been referred to us. By the combined use of pedigree analysis, coagulation assays, and DNA (RFLP) analysis, certainty about the carrier status has been markedly increased for the potential carriers. Although RFLP analysis revealed the possible origin of the mutation in many families with an isolated patient, uncertainty remained for quite a number of their female relatives because of the possible occurrence of germline mosaicism. Forty-one women requested prenatal diagnosis during one or more pregnancies. The short time interval between pregnancies, even after abortion of an affected fetus, proved that first-trimester prenatal diagnosis has become an acceptable option for women at risk. Recently, efficient methods for direct identification of mutations have been developed, and they may allow a definite diagnosis for all families with hemophilia in the near future. PMID- 1739756 TI - Iron stores in 1359, 30- to 60-year-old Danish women: evaluation by serum ferritin and hemoglobin. AB - Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38 micrograms/l, 5-95 percentile 6-135 micrograms/l; 17.2% had values less than 15 micrograms/l (i.e., depleted iron stores), 22.7% values from 15 to 30 micrograms/l (i.e., small iron stores), and 60.1% values greater than 30 micrograms/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54 micrograms/l, 5-95 percentile 10-164 micrograms/l; 10.3% had values less than 15 micrograms/l, 16.5% values from 15 to 30 micrograms/l, and 73.2% values greater than 30 micrograms/l. For the 60-year-old women, median S-ferritin was 84 micrograms/l, 5-95 percentile 25-249 micrograms/l; 1.6% had values less than 15 micrograms/l, 8.6% values from 15 to 30 micrograms/l, and 89.8% values greater than 30 micrograms/l. Blood donors (n = 180) had lower S ferritin than nondonors in all age-groups (p less than 0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 milligrams (8.5 mmol/l), 5-95 percentile 121-152 milligrams (7.5-9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 milligrams (8.7 mmol/l), 5-95 percentile 123-158 milligrams (7.6-9.8 mmol/l) (p less than 0.0001). Hb values less than 121 milligrams (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin less than 15 micrograms/l (n = 161) had lower Hb, median 134 milligrams (8.3 mmol/l), than those with S-ferritin greater than or equal to 15 micrograms/l, median 139 milligrams (8.6 mmol/l) (p less than 0.001). Iron deficiency anemia (S-ferritin less than 15 micrograms/l and Hb less than 121 milligrams) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women. PMID- 1739757 TI - The relevance of cultures of catheter-drawn blood and heparin-lock fluid to diagnose infection in hematologic patients. AB - The results of bacteriologic cultures of blood and heparin-lock fluid, both drawn from the central venous catheters of 54 consecutive oncohematologic patients, have been used to determine their value for the diagnosis of systemic and catheter-associated infection. In 30 patients with clinical signs of infection (bacteremia or septicemia), 74 of 1000 (7.4%) heparin-lock fluid cultures, 114 of 542 (21%) catheter-drawn blood cultures, and 36 of 134 (26%) venipuncture blood cultures became positive, whereas in 24 patients without clinical signs of infection the respective values were 5 of 700 (0.7%), one of 220 (0.4%), and none of ten cultures. Comparison of the results of cultures sampled on the same day reveals that the positive and negative predictive values for catheter-drawn blood cultures, with the venipuncture blood cultures taken as the standard for bacteremia, are 82% and 95% respectively. The results of heparin-lock fluid are indicative for clinically relevant colonization of the catheter. Three or more positive heparin-lock fluid cultures, sampled on subsequent days, were correlated with the occurrence of bacteremia or septicemia with a positive predictive value of 100%. The conclusions are supported by the results of scanning electron microscopy. PMID- 1739758 TI - Acute parvovirus B19 infection mimicking myelodysplastic syndrome of the bone marrow. AB - A 36-year-old, previously healthy woman was referred to our institution with pancytopenia and splenomegaly for suspected acute leukemia. Bone marrow aspiration showed marked dysplastic changes, excess of blasts, and only spurious red blood cell precursors. Action was taken to prepare allogeneic bone marrow transplantation from an HLA identical sibling for myelodysplastic syndrome. Repeat cytological examination of the bone marrow revealed striking hyperplasia of the red cell line with presence of abnormal giant proerythroblasts. Acute parvovirus B19 infection was suspected and confirmed by detection of anti-B19 IgM and B19 DNA. The underlying disease for this transient aplastic crisis was a formerly unknown hereditary spherocytosis. PMID- 1739759 TI - A 53-year-old man with shock and arthritis 1 month after consolidation chemotherapy for acute myeloid leukemia. PMID- 1739760 TI - Defining the cost of health care. PMID- 1739761 TI - Creatively speaking. PMID- 1739762 TI - Family violence Part I. Hidden secrets: elder abuse. PMID- 1739763 TI - Commission sends a clear message: no more business as usual. PMID- 1739764 TI - Watch your language. PMID- 1739765 TI - The price of integrity. PMID- 1739766 TI - [Experiences with digital luminescence radiography (DLR) in pediatric radiology]. AB - X-ray examinations represent a variety of indications with different demands on exposure latitude, spatial and contrast resolution of screen-film-system combinations in paediatric radiography. The value of digital luminescent radiography (DLR) was compared to conventional x-ray examinations carried out with screen-film-systems, speed class 200, by analysing matched digital and conventional exposures in 200 abdominal, 600 skeletal and 300 chest examinations. The exposure of DLR was reduced to 50% of conventional exposure. Analysing the results in abdominal and skeletal radiography, DLR proved to be diagnostically equivalent to conventional radiography despite the reduction in exposure dose. DLR of the newborn chest compared to conventional x-ray studies was not always sufficient due to lower digital spatial resolution. PMID- 1739767 TI - [MR angiography in neuropediatric problems: the technic and the clinical results]. AB - 31 children aged between 6 months and 14 years with various neurovascular abnormalities were examined by MR angiography in a prospective study. In order to test the sensitivity and specificity of the MR results, these were compared in 8 cases with the findings of digital subtraction angiography or conventional angiography. In 24 patients arterial MR angiography was performed; in 17 these showed anomalies or abnormalities of the intracranial vascular system. In 7 patients venous MR angiography was performed and demonstrated the presence of sinus thrombosis in 6 of these. Comparison between MR angiography and DSA showed agreement in 7 cases; in one patient the degree of a stenosis was exaggerated by MR. The results of this study indicate that arterial and venous MR is of great value as an additional study in paediatric neurovascular problems. PMID- 1739768 TI - [MR angiography of the vertebrobasilar circulatory area: the potential uses of the saturation technic to determine the direction of the flow]. AB - MR angiography (MRA) combined with selective saturation techniques has proved to be a reliable method for the determination of flow direction and vascular supply at the level of the circle of Willis. We describe its application to the vertebrobasilar system (VBS) in ten volunteers and five patients with abnormal findings. In one patient with postsurgical stenosis of the brachiocephalic artery, reverse flow of the vertebral artery (VA) was demonstrated. Collateral blood flow from the anterior circulation over the posterior communicating arteries was shown in three patients with bilateral vertebral or proximal basilar artery occlusion. Due to increase of pressure during contrast injection into the contralateral VA, DSA showed reverse flow of a dissected VA in one patient. MR flow determination as well as TCD proved antegrade flow. All results correlated with both DSA and transcranial Doppler (TCD). The technique is little time consuming and is a promising add-on examination to conventional and MRA imaging of the VBS. PMID- 1739769 TI - [Color-coded Doppler sonography of the thyroid: an advance in carcinoma diagnosis?]. AB - There are several papers suggesting that colour-coded Doppler sonography is a useful diagnostic tool for the differentiation of malignant and benign lesions of the thyroid gland. This hypothesis (hypervascularization of malignant nodules) is reconsidered by preoperative examination of 65 patients by using colour-coded Doppler sonography and scintigraphy. Among these patients 21 carcinomas and 2 malignant lymphomas of the thyroid gland were found histologically. Colour-coded Doppler sonography was true positive in 10 cases, true negative in 28 cases, false positive in 14 cases and false negative in 13 cases. Our conclusion is that colour-coded Doppler sonography cannot be used unconditionally for the detection of carcinoma of the thyroid gland. PMID- 1739770 TI - [The signal behavior of parathyroid adenomas in MRT--the contrast ratio of the thyroid and fatty tissue]. AB - A quantitative analysis of signal relationships using T1, proton and T2 weighted spin echo sequences was carried out using 20 parathyroid adenomas demonstrated by MRI. T1 weighted sequences from 15 adenomas were also examined following intravenous injection of Gd-DTPA. No typical signal relationship could be defined. In 4 cases the administration of contrast medium markedly increased the contrast between the adenoma and the thyroid gland. In 12 cases the tumour could be examined histologically following removal. In 2 cases there was oedema of the tumour and corresponding increased intensity of the T2 weighted sequences; in none of the other cases was there any clear correlation between the signals and the histology. PMID- 1739771 TI - [Cervical lymph node metastases. The sonographic demonstration of malignancy]. AB - The value of sonography for demonstrating cervical lymph node metastases has been studied, using longitudinal and transverse measurements as criteria for malignancy. A transverse/longitudinal quotient greater than 2 indicates the presence of metastases with a 96% assurance. Using only longitudinal measurements lymph node metastases can be excluded with only a 36% assurance. The sensitivity of both methods also differs (95% for the maximal transverse quotient as against 90% for longitudinal measurements). The use of the maximal transverse quotient increases specificity from 36 to 96%. This gives sonography an accuracy of 95%. PMID- 1739772 TI - [The findings of color Doppler sonography in breast tumors]. AB - 72 histologically confirmed tumours of the breast--37 carcinomas and 35 benign tumours--for which mammograms were also available were examined by colour Doppler sonography. Vascularisation of benign processes showed at most 2 vessels (with the exception of 3 sarcoma phylloides and one proliferative mastopathy). Vascularisation clearly in excess of benign processes was observed in only 15 of the 37 carcinomas. In 33 of the carcinomas there was no doubt concerning the diagnosis preoperatively, in the remaining 4 the high vascularity was taken as an indication for surgery. CONCLUSION: In rare cases colour Doppler sonography can provide additional information in the presence of 'vascular' tumours. It is not possible to differentiate between poorly vascularised carcinomas and benign tumours. PMID- 1739773 TI - [Intravascular ultrasound (IVUS): the assessment of tumor infiltration into the vascular wall]. AB - The demonstration or exclusion of tumour infiltration into a vessel wall is made possible by IVUS. This was performed 25 times in 23 patients using a 20 MHz probe where there was suspicion of tumour infiltration on the basis of CT, MRI or angiography. IVUS proved very suitable for clarifying the situation, making direct intravascular evaluation of the affected vessel possible. In 10 cases where surgery was performed, the demonstration or exclusion of tumour infiltration into a vein was confirmed operatively in every case. Further experience is necessary before the value of the method for diagnosing early arterial infiltration can be judged. PMID- 1739774 TI - [The extension of MR diagnosis in dissecting aortic aneurysms by means of FLASH and snapshot-FLASH sequences]. AB - Using a combination of T1 weighted snapshot-flash sequences and intravenous contrast bolus it was possible to demonstrate intraluminal signal differences in a period of seconds. 5 confirmed aortic lesions were studied; 2 old aortic dissections (with differentiation between the true and false lumen), 1 acute aortic dissection and a partially thrombosed thoracic aortic aneurysm were demonstrated. The advantage of this technique lies in its simplicity and reproducibility. Difficulties in interpreting the intraluminal phases arising from spin echo and flash techniques are made easier by interpreting the available signals from this method. PMID- 1739775 TI - [The diagnosis of spinal trauma: the indication for CT and myelo-CT on the day of the injury]. AB - During a period of 24 months, 211 patients were investigated in our radiological clinic by emergency CT of the spine on the day of the injury. In 128 (61%) a traumatic lesion could be demonstrated. Most frequently involved were the transitional zones of the spine (occipito-atlanto-axial segment, cervico-thoracic and thoracolumbar segments). In 68% of these patients, conventional radiographs of the spine of these critical zones proved to be inadequate. 20% of the lesions demonstrated by CT could not be seen on conventional radiographs and 41% were shown incompletely. In 61% of cases CT provided additional information when compared with conventional radiography. PMID- 1739776 TI - ["Surgical projection" in the gadolinium-DTPA (Gd-DTPA)-supported NMR tomographic diagnosis of lateral lumbar disk prolapse]. AB - In a group of 25 patients the coronal views of plain and Gd-DTPA-enhanced MRI studies were correlated with CT and operative findings. All series included sagittal, transverse and coronal FLASH sequences (GE 500/6, flip angle 70 degrees), sagittal proton density-(SE 2500/15) and T2-(SE 2500/70) weighted images. MR diagnosis proved to be correct in all cases. Compared to CT and axial MRI herniated disk material in the lateral intravertebral space and its relationship to nerve roots was demonstrated more clearly on coronal views. PMID- 1739777 TI - [A comparison of the value of magnetic resonance tomography and computed tomography in Nelson syndrome patients]. AB - The hypophyses of 13 patients with Nelson syndrome following bilateral adrenalectomy were examined by MRI and CT. Diffuse enlargement of the hypophysis was demonstrated in 8 patients by CT and in 9 by MRI. Compared with CT, MRI provides better demonstration of tumour development, such as abnormal convexity of the cranial margin of the hypophysis (MRI 4/13, CT 1/13), displacement of the infundibulum (MRI 4/13, CT 0/13) or optic chiasm (MRI 2/13, CT 0/13). MRI also provides diagnostically important differentiation between scar tissue and recurrence of tumour following hypophysectomy (MRI 1/3, CT 0/3) and more accurate demonstration of infiltration of the cavernous sinus (MRI 4/13, CT 2/13). CT is superior only in showing the floor of the sella. MRI is the method of choice for imaging in cases of Nelson syndrome. PMID- 1739778 TI - [Gas-forming infections of the extremities]. AB - A variety of cases of gas-forming infections has been collected and the radiological appearances due to the gas formation are described. In the context of the clinical situation the development of gas gangrene can be distinguished from other gas-forming infections which are mostly due to B. coli or cellulitis due to anaerobic streptococci. In addition to describing the pathology and clinical course, the possible forms of treatment are discussed. PMID- 1739779 TI - Diagnostic accuracy of ultrasound-guided fine-needle pancreatic biopsy. AB - We reviewed the results of 187 consecutive ultrasound-guided fine-needle biopsies of the pancreas in 171 patients to assess the diagnostic accuracy of the method. The final diagnosis obtained at operation, autopsy or follow-up were: adenocarcinoma (n = 83), metastatic cancer (n = 11), cystadenocarcinoma (n = 2), lymphoma (n = 2), malignant gastrinoma (n = 1), pseudocyst (n = 25), cyst (n = 13), chronic pancreatitis (n = 9), normal pancreas (n = 10), abscess (n = 7), benign islet-cell tumour (n = 5), cystadenoma (n = 3). Sufficient cytologic material was obtained in 95.3% of biopsies and the overall accuracy in distinguishing benign from malignant disease was 85.4%. False negative results were obtained in 12 patients (13.1%). Inconclusive results (CIII) were found in aspirates from one cyst and two islet cell tumours. There were no false-positive results. The only complication was a post-biopsy haematoma around the head of pancreas, which resolved spontaneously. Ultrasound-guided pancreatic fine-needle biopsy is a safe method and allows of a high degree of diagnostic accuracy. It has a high specificity. Its sensitivity in the detection of malignancy improves if biopsies are repeated in doubtful cases. It further permits tumours to be graded and allows complications of pancreatitis to be diagnosed. PMID- 1739780 TI - [Transcatheter embolization of tumors of the muscular and skeletal systems]. AB - The value of transcatheter embolisation of tumours of the musculoskeletal system is discussed on the basis of 26 cases. All procedures were performed following diagnostic angiography (DSA). By preoperative vascular occlusion it was possible to prevent major blood loss during surgery, provided the operation was carried out within three days of embolisation. Reduction in size of some large inoperable metastases before radio-iodine therapy is another indication for embolisation. As a palliative measure, vascular occlusion can be used for reducing otherwise untreatable skeletal pain and for the management of arteriovenous malformations. Bleeding from a tumour can be controlled by vascular occlusion. Our results indicate that transcatheter embolisation is an effective and reliable technique. PMID- 1739781 TI - [The radiation loading of the crystalline lens and thyroid during high-resolution computed tomography of the teeth]. AB - The radiation dose to the ocular lens and thyroid gland during high resolution CT of the jaw was measured in a head phantom and in 9 patients. The dose for the lens and thyroid gland resulting from 10 cuts was 0.7 and 0.9 mGy, respectively. By shielding the thyroid gland against scatter a reduction of 20% is possible. Radiation exposure is considerably higher than during conventional dental x-ray examinations. Compared with CT examinations of the head and neck region, radiation exposure of both organs is about the same. PMID- 1739782 TI - [The tracheal bronchus as the cause of chronic recurrent pneumonias]. PMID- 1739783 TI - [An unusual complication following the osteosynthesis care of a clavicular fracture]. PMID- 1739784 TI - Computed tomography of retroperitoneal ganglioneuroma. Case report. PMID- 1739785 TI - [Progressive kidney failure due to cholesterol embolization. A complication following arteriography]. PMID- 1739786 TI - [Myositis ossificans progressiva. A case report for the differential diagnosis of ectopic ossification of the cervical spine]. PMID- 1739787 TI - Medical abortion. PMID- 1739788 TI - Ocular injuries from boxing. PMID- 1739790 TI - Fiddling with medical negligence. PMID- 1739789 TI - Swimming and grommets. PMID- 1739791 TI - NHS reforms: the first six months. PMID- 1739792 TI - Aneurin Bevan on the NHS. PMID- 1739793 TI - AIDS now a health risk in Sri Lanka. PMID- 1739794 TI - Childhood mortality after a high dose of vitamin A in a high risk population. AB - OBJECTIVES: To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme. DESIGN: Opportunistic controlled trial. SETTING: Jumla district, Nepal. SUBJECTS: All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation. MAIN OUTCOME MEASURES: Mortality and cause of death in the five months after supplementation. RESULTS: Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0.74, 95% confidence interval 0.55 to 0.99) than in unsupplemented communities. The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133.8 in supplemented children and 260.8 in unsupplemented children (relative risk 0.51, 0.30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0.65, 0.44 to 0.95). The extra cost per death averted was about $11. CONCLUSION: The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost. PMID- 1739795 TI - Stability of essential drugs during shipment to the tropics. AB - OBJECTIVE: To determine whether present methods of international transport of essential drugs by sea adversely affect their quality. DESIGN: Controlled longitudinal study of drug shipments sent by sea from Unicef in Copenhagen to Lagos; to Mombasa and by land to Kampala; and to Bangkok. 11 essential drugs were stored in four locations on board the ships. SETTING: Main shipping routes from Unicef, Copenhagen, to tropical countries. MAIN OUTCOME MEASURES: Temperature and relative humidity in the test packs during the journey. Amount of active ingredient in the drugs before and after shipment. RESULTS: Temperatures recorded within the test packs range from -3.5 degrees C to 42.4 degrees C and were 3-12 degrees C higher than the ambient temperature. Relative humidity within the packs ranged from 20% to 88%. Differences between the locations on board were negligible. Ergometrine injection, methylergometrine injection, and retinol capsules lost 1.5-5.8% of their activity. Ampoules of ergometrine showed a large variation in the amount of active ingredient after shipment, with three of 80 samples having concentrations 60% below those stated. Ampicillin, benzylpenicillin, phenoxymethylpenicillin, and tetracycline were not affected by transport. CONCLUSIONS: Drugs were exposed to a much higher temperature and humidity than is recommended by the manufacturer, especially in tropical harbours and during inland transport. Except for ergometrine and methylergometrine the transport would not affect clinical effectiveness. PMID- 1739796 TI - Mortality and occupational exposure to radiation: first analysis of the National Registry for Radiation Workers. AB - OBJECTIVE: To study cause specific mortality of radiation workers with particular reference to associations between fatal neoplasms and level of exposure to radiation. DESIGN: Cohort study. SETTING: United Kingdom. SUBJECTS: 95,217 radiation workers at major sites of the nuclear industry. MAIN OUTCOME MEASURE: Cause of death. RESULTS: Most standardised mortality ratios were below 100: 83 unlagged, 85 with a 10 year lag for all causes; 84 unlagged, 86 lagged for all cancers; and 80 for all known other causes, indicating a "healthy worker effect." The deficit of lung cancer (75 unlagged, 76 lagged) was significant at the 0.1% level. Standardised mortality ratios were significantly raised (214 unlagged, 303 lagged) for thyroid cancer, but there was no evidence for any trend with external recorded radiation dose. Dose of external radiation and mortality from all cancers were weakly correlated (p = 0.10), and multiple myeloma was more strongly correlated (p = 0.06); for leukaemia, excluding chronic lymphatic, the trend was significant (p = 0.03; all tests one tailed). The central estimates of lifetime risk derived from these data were 10.0% per Sv (90% confidence interval less than 0 to 24%) for all cancers and 0.76% per Sv (0.07 to 2.4%) for leukaemia (excluding chronic lymphatic leukaemia). These are, respectively, 2.5 times and 1.9 times the risk estimates recommended by the International Commission on Radiological Protection, but 90% confidence intervals are large and the commission's risk factors fall well within the range. The positive trend with dose for all cancers, from which the risk estimate was derived, was not significant. The positive association between leukaemia (except chronic lymphatic leukaemia) was significant and robust in subsidiary analyses. This study showed no association between radiation exposure and prostatic cancer. CONCLUSION: There is evidence for an association between radiation exposure and mortality from cancer, in particular leukaemia (excluding chronic lymphatic leukaemia) and multiple myeloma, although mortality from these diseases in the study population overall was below that in the general population. The central estimates of risk from this study lie above the most recent estimates of the International Commission on Radiological Protection for leukaemia (excluding chronic lymphatic leukaemia) and for all malignancies. However, the commission's risk estimates are well within the 90% confidence intervals from this study. Analysis of combined cohorts of radiation workers in the United States indicated lower risk estimates than the commission recommends, and when the American data are combined with our analysis the overall risks are close to those estimated by the commission. This first analysis of the National Registry for Radiation Workers does not provide sufficient evidence to justify a revision in risk estimates for radiological protection purposes. PMID- 1739797 TI - Detection of functional iron deficiency during erythropoietin treatment: a new approach. PMID- 1739798 TI - Health promotion in the general practice consultation: a minute makes a difference. AB - OBJECTIVE: To see whether extending appointment length from seven and a half minutes or less to 10 minutes per patient would increase health promotion in general practice consultations. DESIGN: Controlled trial of 10 minute appointments. Consultations were compared with control surgeries in which the same doctors booked patients at their normal rate (median six minutes per patient). SETTING: 10 general practices in Nottinghamshire. SUBJECTS: 16 general practitioners were recruited. Entry criteria were a booking rate of eight or more patients an hour, a wish for longer consultations, and plans to increase appointment length. MAIN OUTCOME MEASURES: Duration of consultations; recording of blood pressure, weight, and cervical cytology in the medical record; recording of advice about smoking, alcohol, diet, exercise, and immunisation in the medical record; reporting of the above activities by patients. RESULTS: Mean consultation times were 8.25 minutes in the experimental sessions and 7.04 and 7.16 minutes in the control sessions. Recording of blood pressure, smoking, alcohol consumption, and advice about immunisation was significantly more frequent in the experimental sessions, and the proportion of consultations in which one or more items of health education were recorded in the medical notes increased by an average of over 6% in these sessions. Patients more often reported discussion of smoking and alcohol consumption and coverage of previous health problems in the experimental sessions. There was little change in discussion of exercise, diet, and weight or cervical cytology activity. CONCLUSIONS: Shortage of time is a major factor in general practitioners' failure to realise their potential in health promotion. General practice should be organised so that doctors can run 10 minute appointment sessions. PMID- 1739799 TI - Managing change in general practice: a step by step guide. PMID- 1739800 TI - Quality management in the NHS: the doctor's role--I. PMID- 1739801 TI - Prescribing in Europe--forces for change. PMID- 1739802 TI - Swimming--the hazards of taking a dip. PMID- 1739803 TI - ABC of vascular diseases. Late complications of arterial grafts. PMID- 1739804 TI - A patient's charter for laboratories. PMID- 1739805 TI - Prescribing at the hospital--general practice interface. PMID- 1739806 TI - Auditing necropsies. PMID- 1739807 TI - Communication of results of necropsies. PMID- 1739808 TI - Hormonal manipulation of prostatic cancer. PMID- 1739809 TI - Vision screening in preschool children. PMID- 1739810 TI - Vision screening in preschool children. PMID- 1739811 TI - Auditing audits. PMID- 1739812 TI - The EPIC study. PMID- 1739813 TI - Lessons of Chernobyl. PMID- 1739814 TI - Understanding Marfan's syndrome. PMID- 1739815 TI - Health of the nation: personality disorder. PMID- 1739816 TI - Nursing comes of age. PMID- 1739817 TI - Disposal of clinical waste. PMID- 1739818 TI - First among women. PMID- 1739819 TI - Randomized clinical trials in general practice. PMID- 1739820 TI - Reducing risks in the sudden infant death syndrome. PMID- 1739821 TI - Relabelling blood. PMID- 1739822 TI - What mentally ill offenders need. PMID- 1739823 TI - Airs, waters, places, and doctors. PMID- 1739824 TI - Systemic vasculitis. PMID- 1739825 TI - Junior doctors on the warpath. PMID- 1739826 TI - Thermal environment and sudden infant death syndrome: case-control study. AB - OBJECTIVE: To compare the thermal environment of infants who died of the sudden infant death syndrome with that of age matched control infants. DESIGN: Case control study. Infants who died were matched with two controls, one for age and one for age and birth weight. Thermal measurements were conducted at the death scene for cases and at the scene of last sleep for control infants, who were visited unexpectedly within four weeks of the index infant's death on a day of similar climatic conditions. A follow up questionnaire was administered to parents of cases and controls. SETTING: The geographical area served by the professional Tasmanian state ambulance service, which includes 94% of the Tasmanian population. SUBJECTS: 41 infants died of the sudden infant death syndrome at home; thermal observations at death scene were available for 28 (68%), parental questionnaire data were available for 40 (96%). 38 controls matched for age and 41 matched for age and birth weight. RESULTS: Cases had more excess thermal insulation for their given room temperature (2.3 togs) than matched controls (0.6 togs) (p = 0.009). For every excess thermal insulation unit (tog) the relative risk of the sudden infant death syndrome was 1.26 (95% confidence interval 1.05 to 1.52). The average thermal bedding value calculated from parental recall was similar to that observed by attendant ambulance officers (mean difference = 0.4 tog, p = 0.39). Cases were more likely to have been found prone (odds ratio 4.58; 1.48 to 14.11). Prone sleeping position was not a confounder or effect modifier of the relation between excess thermal insulation and the syndrome. CONCLUSIONS: Overheating and the prone sleeping position are independently associated with an increased risk of the sudden infant death syndrome. Further work on infant thermal balance and sudden infant death is required and guidelines for appropriate infant thermal care need to be developed. PMID- 1739827 TI - Can the fall in Avon's sudden infant death rate be explained by changes in sleeping position? AB - OBJECTIVE: To examine the impact of changing practice with regard to infant sleeping position on mortality from the sudden infant death syndrome. DESIGN: A population based study of all infants dying suddenly and unexpectedly during February 1990 to July 1991, and two groups of controls; one comprising every 125th baby born to Avon residents and the other comprising pairs of infants matched to each index case for age, neighbourhood, and date of study. Information about sleeping position was collected at home visits soon after the index baby's death or, for the population based controls, on several occasions in the first six months of life. The design was comparable to that of an earlier study of the same population. SETTING: County of Avon. SUBJECTS: 35 infants who died suddenly and unexpectedly (32 of the sudden infant death syndrome), 70 matched controls, and 152 population based controls. RESULTS: The prevalence of prone sleeping in the matched controls was much lower than that found in an earlier study in Avon (28% (18/64) 1990-1 v 58% (76/131) 1987-9; p less than 0.001) and was comparable with the prevalence in population based controls (29%). This would be expected to lead to a reduction in the incidence of the sudden infant death syndrome to 2.0/1000 live births (95% confidence interval 1.8/1000 to 2.5/1000). The actual mortality fell from 3.5/1000 in 1987-9 to 1.7/1000. CONCLUSION: The fall in mortality can be almost entirely accounted for by the reduction in prone sleeping, suggesting a causal relation exists between them. Side and supine positions confer protection but the side position is unstable and the infant may roll prone. We therefore recommend supine as the safest sleeping position for babies. PMID- 1739828 TI - Increased risk of death from measles in children with a sibling of opposite sex in Senegal. AB - OBJECTIVE: To examine whether contracting measles from a sibling of the opposite sex affects mortality. DESIGN: Prospective registration during 15-20 years of all births and deaths, including 243 measles related deaths. Measles infection was not registered; however, as in fatal cases measles was probably contracted from a maternal sibling the risk of dying during measles outbreaks was examined in families with two boys, two girls, or a boy and a girl. SETTING: 31 small villages in two rural areas of eastern Senegal. SUBJECTS: 766 children living in families with two children aged under 10 years during outbreaks of measles, 107 (14%) of whom died of measles. MAIN OUTCOME MEASURE: Deaths from measles, size of village, age and sex of maternal siblings. RESULTS: The interval between outbreaks in the same village was greater than 10 years. The risk of dying of measles was significantly related to age, increasing with the age difference between siblings and decreasing with the size of village. In a multiple logistic regression analysis adjusting for these background factors, children in families with a boy and a girl had a significantly higher mortality than children in families with two boys or two girls (odds ratio = 1.81, 95% confidence interval 1.17 to 2.82). The increase in risk was the same for boys and girls in families with two children one of whom was a boy and one a girl. CONCLUSION: Cross sexual transmission may be an important determinant of severity of measles infection. PMID- 1739829 TI - Geriatric visiting hours: lessons for the general wards? PMID- 1739830 TI - Establishment of pregnancy after removal of sperm antibodies in vitro. PMID- 1739831 TI - Uncomfortable prescribing decisions: a critical incident study. AB - OBJECTIVE: To explore the discomfort experienced by general practitioners in relation to decisions about whether or not to prescribe. DESIGN: Focused interviews of general practitioners about prescribing decisions that made them uncomfortable. Analysis based on the critical incident technique. SETTING: One family practitioner committee area in the north of England. RESPONDENTS: 69 principals and five trainee general practitioners. MAIN OUTCOME MEASURES: Drugs and clinical problems associated with prescribing discomfort. Reasons given by doctors for making the prescribing decisions they did and reasons for feeling uncomfortable. RESULTS: Antibiotics, tranquillisers, hypnotics, and symptomatic remedies were most often associated with discomfort, but any prescribable item could be associated with discomfort. Respiratory diseases, musculoskeletal problems, and anxiety were most often associated with discomfort, but again any condition could be associated. The main reasons given for the decisions made were patient expectation, clinical appropriateness, factors related to the doctor patient relationship, and precedents. The main reasons given for feeling uncomfortable were concern about drug toxicity, failure to live up to the general practitioner's own expectations, concern about the appropriateness of treatment, and ignorance or uncertainty. CONCLUSIONS: Many considerations, including medical, social, and logistic ones, influence the decision to prescribe in general practice. The final action taken depends on a complex interaction of these disparate influences. PMID- 1739832 TI - Re-examining the fundamental principles of the NHS. PMID- 1739833 TI - Environmental radiation: a cause for concern? PMID- 1739834 TI - Quality management in the NHS: the doctor's role--II. PMID- 1739835 TI - Occupational causes of disorders in the upper limb. PMID- 1739836 TI - Hazards of pharmacological tests of growth hormone secretion. PMID- 1739837 TI - Searching published reports. PMID- 1739838 TI - Hazards of pharmacological tests of growth hormone secretion. PMID- 1739839 TI - Failed hip replacements. PMID- 1739840 TI - Voice after laryngectomy. PMID- 1739841 TI - Voice after laryngectomy. PMID- 1739842 TI - Voice after laryngectomy. PMID- 1739843 TI - Overheads for clinical research. PMID- 1739844 TI - Deciding whether to be a doctor. PMID- 1739845 TI - High potency factor VIII concentrates. PMID- 1739846 TI - Impact resistance of drinking glasses. PMID- 1739847 TI - Diazoxide no longer marketed. PMID- 1739848 TI - Post-comatose unawareness? PMID- 1739849 TI - Developmental levels of social cognition in head-injury patients. AB - Ten adults, who had sustained a closed head injury, were interviewed regarding their self-understanding, concepts of persons, and interpersonal negotiation strategies. Responses were evaluated in terms of developmental levels of social cognition. Levels of interpersonal negotiation strategies were significantly lower than levels of self-understanding, descriptions of psychological characteristics of self were at a significantly higher level than descriptions of active and physical characteristics of self. Within interpersonal conflict situations, proposed solutions were at a significantly lower level than the justifications offered for the solutions. In general, developmental levels of social cognition were comparable to levels exhibited by non-clinical samples of adolescents. The two areas in which the head-injury patients appeared to perform at a significantly higher level than adolescents were their justifications for their proposed solutions to the interpersonal conflict situations and their ability to express the emotional consequences of interpersonal conflict. PMID- 1739850 TI - Premorbid emotional and behavioural adjustment in children with mild head injuries. AB - This study investigated the hypothesis that children sustaining a mild closed head injury have a higher prevalence of premorbid behavioural problems than children in the general community. The prevalence of emotional and behavioural problems among children with a mild closed head injury was compared with the prevalence of problems in children with a severe closed head injury, children in the general community, and children referred to a psychiatric outpatient clinic. The results showed that the children with a mild head injury did not have significantly more premorbid emotional and behavioural problems than other children in the community. The children with a mild head injury also had significantly fewer emotional and behavioural problems than children referred to a psychiatric outpatient clinic. The results suggest that the common assumption that children with a mild closed head injury have a higher prevalence of premorbid emotional and behavioural problems than other children in the general community may not be correct. PMID- 1739851 TI - Language abilities of mildly closed head injured (CHI) children 10 years post injury. AB - The language functioning of a group of 14 children who had sustained a mild closed head injury (CHI) at least 10 years previously was assessed. The subjects were administered a battery of language assessments including an overall language test, and specific language skills assessments. Performance of the head-injured group was compared with that of a group of non-neurologically impaired accident victims matched for age, sex and educational level. Overall language performance of the experimental group did not differ significantly from the controls. PMID- 1739852 TI - Long-term neuropsychological outcome after severe head injury with good recovery. AB - The quality of outcome after severe closed head injury has become of increasing concern to neurosurgeons. The assessment of residual deficits in patients who have recovered from closed head injury can be very difficult. Many patients are classified as having a good recovery according to the Glasgow Outcome Scale (GOS), but this may be insufficiently focused or sensitive to demonstrate mental deficits objectively. We investigated 33 patients with severe closed head injury who subsequently were diagnosed as having made a good recovery according to the GOS. The severity of the injury was determined by the Glasgow Coma Scale (GCS) and by the presence of a midline shift in the preoperative CT scans. There was a minimal interval of 15 months (means = 1080.5 days, SD = 491 days) between injury and time of neuropsychological testing. Their performance was compared with that of 15 orthopaedic cases. Residual neuropsychological deficits can be demonstrated on the majority of measures in a group of patients who have achieved good recovery on the GOS. Midline shift in preoperative CT scans is not of prognostic value for long-lasting neuropsychological deficits. PMID- 1739853 TI - Rehabilitation staff stress as it relates to patient acuity and diagnosis. AB - Significant concern exists regarding occupational stress among nurses; the present study explored the ways in which nurses' clinical symptoms and coping styles may relate to their working on a brain injury unit or a general rehabilitation unit within an acute physical rehabilitation hospital. A comparison of rehabilitation nurses' responses with those of physical therapists within the same setting was also completed. Staff members completed questionnaires related to job stress and satisfaction, coping (Ways of Coping Checklist) and adjustment (Symptom Checklist-90). Staff groups differed with regard to symptomatology. Brain injury nurses reported higher psychological distress than physical therapists on subscales including depression, interpersonal sensitivity and the global severity index. While brain injury nurses' distress in several areas was higher than other staff groups and than a normal non-patient sample, it did not approach the levels reported by a psychiatric outpatient normative group. Although the three staff groups did not differ notably with regard to most styles of coping, data suggest that work with brain injury patients may foster use of a problem-solving style. Lower physical and cognitive functioning of brain patients as compared with general rehabilitation patients may influence the greater psychological distress reported by brain injury nurses. Job stress appears to relate specifically to the perceived stressfulness of cognitive behavioural aspects of care for all staff groups. Implications of these findings, particularly with regard to support interventions, are discussed. PMID- 1739854 TI - Executive and compensatory memory retraining in traumatic brain injury. AB - A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre- and post test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented. PMID- 1739855 TI - Late improvement in closed head injury with a low-pressure valve shunt. PMID- 1739856 TI - Problems in magnetic resonance imaging of patients with severe brain injury and a solution to one of them. AB - A number of difficulties have been encountered in carrying out MRI scans with severely brain-injured subjects. One of the problems is maintenance of head position for the 30 minutes' duration of the scan. The use of a vacuum cushion has proved a low-cost solution to this problem. PMID- 1739857 TI - Use of AA and NA in the treatment of chemical dependencies of traumatic brain injury survivors. AB - Alcoholics Anonymous and Narcotics Anonymous have been under-utilized in the treatment of chemical dependency in traumatic brain injury survivors. Both offer a social support network and a self-help recovery programme. The fellowships can be viewed as three progressive levels focusing on behavioural, cognitive and gestalt issues. Finally observations and suggestions are offered which may help in incorporating this therapeutic modality which is the most widespread treatment of individuals with chemical dependencies. PMID- 1739858 TI - Coping strategies and locus of control following traumatic brain injury: relationship to long-term outcome. AB - Cluster-analytic techniques were used to categorize coping strategies (CS) measured by the Ways of Coping--Revised Scale, and locus of control (LOC) beliefs measured by the Multidimensional Health Locus of Control Scale in 53 male traumatically brain-injured (TBI) persons. A cluster characterized by comparatively higher use of self-controlling and positive reappraisal CS and lower external LOC was associated with significantly lower mood disturbance and physical difficulties and a trend to be less depressed. The age of the neurologically injured patient and Taylor's (1983) cognitive adaptation theory may be important aspects of recovery from TBI and other neurological conditions. PMID- 1739859 TI - Coma arousal intervention. PMID- 1739860 TI - British Society for Rheumatology, spring meeting. Southampton, 26-27 March 1992. Abstracts. PMID- 1739861 TI - Advances in innovative oncology: biomodulation, chemoimmunotherapy, and selected Phase II drugs. Proceedings of The Chemotherapy Foundation. November 7-8, 1991, New York City, USA. Abstracts. PMID- 1739862 TI - Physical and biochemical factors in bone metabolism. PMID- 1739863 TI - Effect of calcitonin on bone histomorphometry and bone metabolism in rheumatoid arthritis. AB - Twenty-four women (mean age +/- SD 49 +/- 13 years) with classical or definite rheumatoid arthritis (disease duration 15 +/- 8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P less than 0.001). There was also a significant increase (P less than 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA. PMID- 1739864 TI - Cross-cultural association between dietary animal protein and hip fracture: a hypothesis. AB - Age-adjusted female hip fracture incidence has been noted to be higher in industrialized countries than in nonindustrialized countries. A possible explanation that has received little attention is that elevated metabolic acid production associated with a high animal protein diet might lead to chronic bone buffering and bone dissolution. In an attempt to examine this hypothesis, cross cultural variations in animal protein consumption and hip fracture incidence were examined. When female fracture rates derived from 34 published studies in 16 countries were regressed against estimates of dietary animal protein, a strong, positive association was found. This association could not plausibly be explained by either dietary dietary calcium or total caloric intake. Recent studies suggest that the animal protein-hip fracture association could have a biologically tenable basis. We conclude that further study of the metabolic acid-osteoporosis hypothesis is warranted. PMID- 1739865 TI - Influence of body weight on rates of change in bone density of the spine, hip, and radius in postmenopausal women. AB - Interrelationships between percent of ideal body weight (%IBW), serum estrogen levels, and change in bone mineral density (delta BMD) and bone mineral content (delta BMC) were studied in 288 postmenopausal women aged 41-71 years who participated in a 2-year calcium supplement trial. The spine (L2-L4) and femoral neck were measured by dualphoton absorptiometry, and the radius was measured by single-photon absorptiometry. Years since menopause, calcium intake, and initial BMD or BMC were included as independent variables in two-phase regressions of delta BMD and delta BMD on %IBW. Increased %IBW protected against loss of spine BMD [regression slope estimate = 0.05, 95% C.I.: (0.03, 0.26)] and BMC in women up through about 106 %IBW but not in heavier women. Increased %IBW was not significantly related to delta BMD or delta BMC at the femoral neck or radius. Women above 106 %IBW had significant gains in spine and femoral neck area (P less than 0.05). Serum estrone and estradiol were positively correlated with delta BMD and delta BMC at the femoral neck only. PMID- 1739866 TI - Sex differences in geometry of the femoral neck with aging: a structural analysis of bone mineral data. AB - The greater hip fracture rate among elderly women is generally ascribed to differences in femoral neck strength between the sexes. Strength of a given bone is a function of both its material properties and the magnitudes of mechanical stresses within it. This study examined the hypothesis that these apparent strength differences between the sexes are due to dissimilarities in the restructuring of the femoral neck with age, which result in higher stresses in elderly women. Using Hip Strength Analysis, a computer program developed by the authors, femoral neck cross-sectional geometric properties for stress analyses were derived from bone mineral image data of 409 community living, white subjects ranging from 19 to 93 years of age. Though both sexes show declines in femoral neck bone mineral density (BMD) and cross-sectional area with age, only females show a decline in the cross-sectional moment of inertia (CSMI, a geometric index of bone rigidity). The lack of decline in male CSMI appears to be a result of a small but significant increase in femoral neck girth. Similar age-related changes have been observed in the femoral shaft by others. The net effect of these observed changes is that mechanical stresses in the femoral neck of females appear to increase at three times the rate per decade of those of males. These results lend support to the hypothesis that the higher fracture rate in elderly women is due, at least in part, to elevated levels of mechanical stress, resulting from a combination of greater bone loss and less compensatory geometric restructuring with age. PMID- 1739867 TI - Discriminatory ability of bone mass measurements (SPA and DEXA) for fractures in elderly postmenopausal women. AB - We investigated the discriminatory ability of forearm bone mineral content (BMCarm) measured by single photon absorptiometry (SPA) and spinal bone mineral density (BMDspine) measured by dual-energy X-ray absorptiometry (DEXA) in 387 elderly postmenopausal women. Of these, 22 had never sustained a fracture (normal), 91 had had less than three vertebral wedge fractures (mild), 51 had experienced a peripheral fracture (moderate), and 24 had had more than three vertebral wedge or compression fractures (severe). BMCarm exceeded BMDspine slightly in the ability to discriminate the mild and moderate groups (P less than 0.01-0.001), whether calculations were performed on raw values or the Z-scores compared with premenopausal women. Receiver operating (ROC) analysis showed that at every cutoff level BMCarm had a similar ability as BMDspine to discriminate between the vertebral fracture (mild and severe) groups and healthy premenopausal and nonfractured postmenopausal women (normal), whereas BMCarm had a significantly higher discriminatory ability of peripheral fractures (P less than 0.05) (moderate) group compared with premenopausal women. We conclude that SPA and DEXA are equally capable as diagnostic procedures in women with established osteoporosis. PMID- 1739868 TI - Osteogenesis imperfecta: a clinical study of the first ten years of life. AB - One hundred twenty-seven children with osteogenesis imperfecta (O.I.) were studied during the first 10 years of life. According to Sillence, 40 patients were assigned to type I, 39 to type III, and 48 to type IV O.I. Centiles for height, weight, and the annual number of fractures could be established for the different types of O.I. The development of the skeletal changes could be documented for the different forms of the disease. At birth, the skeletal changes were significantly more severe in type III than in type IV patients. During the first 10 years of life the number of fractures, extent of skeletal deformities, and growth retardation did not differ between types III and IV. Only fracture nonunion, dentinogenesis imperfecta, and congenital cardiac malformations were more frequent in type III than in type IV. Papillary calcifications of the kidney and kidney stones were diagnosed in 4 type III and 2 type IV patients. Hemihypertrophy of the body developed in 2 type I patients. Although types III and IV patients suffered from severe short stature, serum insulin-like growth factor (IGF) I was in the normal range. PMID- 1739869 TI - Characterization of very young mineral phases of bone by solid state 31phosphorus magic angle sample spinning nuclear magnetic resonance and X-ray diffraction. AB - The properties of bone mineral change with age and maturation. Several investigators have suggested the presence of an initial or "precursor" calcium phosphate phase to help explain these differences. We have used solid state 31P magic angle sample spinning (MASS) nuclear magnetic resonance (NMR) and X-ray radial distribution function (RDF) analyses to characterize 11- and 17-day-old embryonic chick bone and fractions obtained from them by density fractionation. Density fractionation provides samples of bone containing Ca-P solid-phase deposits even younger and more homogeneous with respect to the age of mineral than the calcium phosphate (Ca-P) deposits in the whole bone samples. The analytical techniques yield no evidence for any distinct phase other than the poorly crystalline hydroxyapatite phase characteristic of mature bone mineral. In particular, there is no detectable crystalline brushite [DCPD, CaHPO4 2H2O less than 1%] or amorphous calcium phosphate (less than 8-10%) in the most recently formed bone mineral. A sizeable portion of the phosphate groups exist as HPO4(2-) in a brushite (DCPD)-like configuration. These acid phosphate moieties are apparently incorporated into the apatitic lattice. The most likely site for the brushite-like configuration is probably on the surface of the crystals. PMID- 1739870 TI - Biphasic dose-response curves of cortisol effects on rat diaphyseal bone biomechanics. AB - Doses of 8, 16 (low), 32, 48, 64 (medium), and 150 (high) mg/kg/day of cortisol were administered to groups of 8 growing rats each during 16 days, and their femurs were then submitted to 3-point bending tests at low strain rate. Low doses had no effect. Medium doses, previously shown to improve calcium (Ca) balance and weight gain in the species, augmented diaphyseal elastic and ultimate strength, stiffness, and plastic-to-elastic deformation ratio with respect to untreated controls. This effect was achieved either by enhancing bone mass (volume, sectional moment of inertia, wall/lumen ration) without changes in material quality parameters (32 mg/kg/day) or, conversely, by increasing bone tissue mechanical properties (stress, modulus of elasticity) not affecting bone geometry (48 and 64 mg/kg/day). The highest dose, known to depress Ca balance and weight gain, impaired diaphyseal mechanical performance in controls by substantially reducing bone mass without major variation in bone material properties, that is, developing a true osteopenic state in mechanical terms. The energy elastically absorbed per unit volume (proportional to the risk of comminute fractures) was greater with the highest dose because of enhanced deformability and diminished bone mass. The biphasic dose-response curves obtained, grossly parallel to those previously demonstrated for metabolic actions of cortisol in the same species, showed that biomechanical repercussion of this treatment on bone depends on different, dose-dependent effects which vary independently in temporal course, intensity, and sign. PMID- 1739871 TI - Vertebral fracture or vertebral deformity. PMID- 1739872 TI - Effect of membrane cholesterol on calcium phosphate formation in aqueous suspensions of anionic liposomes. AB - The present study examined the effect of membrane cholesterol on liposome mediated calcium phosphate precipitation in metastable aqueous solutions (2.25 mM Ca2+ and 1.5 mM inorganic phosphate) at 22 degrees C, pH 7.4 and 240 mOsm. The liposomes were prepared from 7:2:X molar mixtures of phosphatidylcholine, dicetylphosphate, and cholesterol (x = 0, 1, 5, or 9) and contained either 0 or 50 mM encapsulated phosphate. The membranes were made permeable to Ca2+ by addition of the cationophore, X-537A. Changes in external Ca2+ concentration were used as the principal monitor of the course of precipitation. Without encapsulated phosphate, 7:2:X liposomes (with or without ionophore) induced no precipitation. With 50 mM encapsulated phosphate and in the presence of ionophore, precipitation significantly depended on the cholesterol level in the membrane. At 0 and 10 mole% cholesterol, precipitate developed rapidly both within and outside the liposomes. At 35 and 50 mole% cholesterol, no observable intraliposomal precipitation occurred, and extraliposomal precipitation started only after an induction period of 24 hours. Delayed extraliposomal precipitation also took place in PO4-containing liposomes without added ionophore. In this latter case, however, cholesterol was essential for this precipitation to occur with the optimum level being around 10 mole%. Suppression of ionophore-mediated intraliposomal precipitation at higher cholesterol levels could be related to the inflexible cholesterol molecules making the membrane more rigid, thereby restricting Ca-ionophore transport. This restriction could be reversed with ethanol. Delayed extraliposomal precipitation in the absence of added ionophore (or at higher cholesterol levels in its presence) could be explained by seeding from low, unobserved levels of intraliposomal precipitate formed during slow, unfacilitated Ca2+ leakage into the liposomal interior. PMID- 1739873 TI - Three-year calcitonin combination therapy for postmenopausal osteoporosis with crush fractures of the spine. AB - Forty-five postmenopausal osteoporotic women with at least one osteoporotic vertebral crush fracture were randomized into three treatment groups. Each patient was on calcitonin, 50 U, on alternate days for 2 weeks monthly (350 U/month), and 500 mg/day oral calcium supplementation. In group II, this therapy was supplemented with phosphate (750 mg/day), and in group III, norandrostenolone decanoate (50 mg/month) was added to the calcitonin+calcium therapy. Bone mineral content, by single photon absorptiometry, of the radius midshaft and distal site (3 cm), as well as the lumbar and metacarpal radiomorphometrical indices were estimated seminannually. The therapeutic trial lasted 36 months except in the phosphate supplementation group, where, due to unfavorable results, treatment was discontinued after 24 months. Calcitonin practically prevented further bone loss for 24 months even in this relatively small and intermittent dosage. Phosphate supplementation was without benefit; however, according to the majority of the examined parameters, combination of calcitonin with the anabolic steroid norandrostenolone decanoate extended efficacy up to 36 months. This latter combination seems to be a promising, relatively inexpensive therapeutic regimen in the treatment of established postmenopausal osteoporosis. PMID- 1739874 TI - Osteonal remodeling and mechanical properties of the femoral cortex in rabbits treated with 24R,25(OH)2D3. AB - The increase of bone mass by therapeutics does not always mean the enhancement of bone quality. The purpose of this study is to clarify the changes of osteonal remodeling and the mechanical properties of femoral cortex in rabbits treated with 24R,25(OH)2D3. Fifteen NZW rabbits (3 kg B.W.) were divided into three groups of 5 animals each. Groups 1, 2, and 3 were given vehicle, 10 micrograms/kg, and 100 micrograms/kg 24R,25(OH)2D3, respectively, daily for 8 weeks. At the end of the experiment, the left femur was removed and bone mineral content (BMC) was measured with single photon absorptiometry. Serum 24,25(OH)2D concentrations reached levels of approximately 15 and 200 times that of the controls in groups 2 and 3, respectively. Neither 25(OH)D nor 1,25(OH)2D level showed any significant change in either group. Group 3 showed significant increase in mineral content and density in the epimetaphyseal regions, but the increase at the diaphyseal region did not reach a statistically significant level. Mechanical test for torsion was conducted for mid-cortical regions. After the test, bone pieces were bonded together with adhesive to reconstruct the original form, and undecalcified cross-sectional sections were made at the diaphyses. Fluorescent microscopy disclosed a marked reduction of remodeling in secondary osteonal bone area. The numbers for double-labeled osteons for groups 1, 2, and 3 were 2.47 +/- 0.819, 1.14 +/- 1.02* and 0.137 +/- 0.307* N/mm2, respectively, and the numbers for osteons with resorption lacunae were 1.37 +/- 0.721, 0.412 +/- 0.370* and 0.268 +/- 0.339** N/mm2, respectively. However, neither structural stiffness nor strength correlated with the indices of osteonal remodeling; instead, they were significantly correlated with bone mineral contents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739876 TI - Effect of fluoride dosage on bone density, sonic velocity, and longitudinal modulus of rabbit femurs. AB - Relationships between the fluoride dosage administered to weanling New Zealand white male rabbits and some mechanical properties of the compact bone were investigated for a wide range of dosages. The measured quantities were density, longitudinal sonic velocity in the radial direction, and fluoride ion concentration in compact bone. The longitudinal elastic modulus was estimated from the product of the density and the square of the sonic velocity. The relative static load stress was estimated from the ratio of the final body weight to the cross-sectional area of the femur. These measurements and derived quantities provide quantitative measures of bone quality. A slight peak (2% greater than reference) was determined for the density and a slightly larger peak (5% above reference) for the longitudinal sonic velocity at a dosage of approximately 20 mg/kg/day. The longitudinal elastic modulus exhibited a substantial peak, 14% greater than reference. The relative static load stress showed a very slight peak as a function of dosage and also as a function of fluoride concentration in the bone. When plotted against the elastic modulus, a nonlinear monotonic increase was observed with modulus, showing that the cross sectional area of the bone is responsive to the stiffness of the tissue. Stiffer tissue produces a smaller cross section, whereas a more compliant tissue requires a marked increase in the area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1739875 TI - Production of new trabecular bone in osteopenic ovariectomized rats by prostaglandin E2. AB - Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of age-matched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the dose-response manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats. PMID- 1739877 TI - Characterization of osteoblast-like cells from normal adult rat femoral trabecular bone. AB - Osteoblast-like cell cultures have been established from the trabecular surfaces of normal adult rat femoral trabecular bone. The cultured cells responded to stimulation by parathyroid hormone (rPTH), with a rise in intracellular cAMP in excess of 25-fold while failing to respond to incubation with sCT. Furthermore, the osteoblast-like cells exhibited a high level of alkaline phosphatase expression, both histochemically and biochemically. Incubations with 1,25(OH)2 vitamin D3 increased the alkaline phosphatase activity by 50% and stimulated bone Gla-protein (BGP) synthesis. When the cell layers were supplemented with both 50 micrograms/ml ascorbic acid and 10 mM beta-glycerophosphate and allowed to grow past confluency for 3 weeks, they formed calcified ridges and multilayered nodules. Confirmation of the mineralization of an extracellular matrix was made by von Kossa staining. This simple isolation technique now facilitates the availability of normal adult rat osteoblastic cells for investigation of bone and mineral metabolism. PMID- 1739878 TI - Sodium fluoride does not increase human bone cell proliferation or protein synthesis in vitro. PMID- 1739879 TI - Compact bone and fracture risk. PMID- 1739880 TI - Management of xerostomia. AB - Xerostomia (dry mouth) is an unpleasant condition that is common after radiotherapy to the head and neck, although it may have other causes. A review of the management of xerostomia, as well as the prevention and management of the oral soft tissue and dental complications resulting from xerostomia, is provided. PMID- 1739881 TI - The base metal alloy question in removable partial dentures--a review of the literature and a survey of alloys in use in Alberta. AB - Base metal alloys have been used for over 60 years to cast removable partial denture frameworks. Among other elements, these alloys principally contain nickel, chromium and cobalt, and may be divided into the nickel-containing and nickel-free alloys. Because of the potential biocompatibility hazard created by these and other elements found in the alloys, this group of materials has come under ever increasing scrutiny in the literature. This paper reviews pertinent literature and reports on the findings of a survey on the base metal alloys used in Alberta for the casting of removable partial denture frameworks. PMID- 1739882 TI - Computerized databases: privacy issues in the development of the nursing minimum data set. AB - Nursing leaders promoting the development and use of computerized databases such as the Nursing Minimum Data Set (NMDS) have not adequately addressed the complex ethical issues involved with computerized information systems. The purpose of this article is to describe the privacy issues involved with the NMDS. Moral considerations and principles guiding resolution of ethical issues concerning violations of patient privacy are discussed. A paradigm case is used to demonstrate the significance of privacy violations in computerized databases. Two security systems currently being considered in other disciplines are included for their relevance to the development of the NMDS. The broader implications concerning the impact of technology on preservation of human dignity and the quality of life are addressed. PMID- 1739883 TI - Computer-supported versus manually-generated nursing care plans: a comparison of patient problems, nursing interventions, and AIDS patient outcomes. AB - The number and type of activated patient problems and the number of nursing interventions in computer-supported and manually-generated nursing care plans for Human Immunodeficiency Virus (HIV) infected patients hospitalized for Pneumocystis carinii pneumonia (PCP) were compared. There were significantly more activated patient problems (p = 0.005) and nursing interventions (p = 0.002) listed using the computer-supported care planning system. The top ranked problems in both systems were reflective of the clinical presentation of acute PCP. The problem, potential for increased risk of infection, was activated more frequently using the computer-supported care plan. There were no significant differences in patient outcome as measured by functional status and patients' self-ratings of physical condition at hospital discharge. PMID- 1739884 TI - A computer-based AIDS education program for nursing students. AB - A multidisciplinary team has developed a computer-based software program for educating nursing students and other college students about six sexually transmitted diseases (STDs). The program for educating about Acquired Immune Deficiency Syndrome (AIDS) is the first of the six "Smartbooks" to be completed, using the Hypercard Expert System shell on the Macintosh computer. Information is organized within a framework known as a concept map, and the student user progresses through the program in a self-directed way by "clicking" on the portion of the concept map that is of interest. Thus, the knowledge base can be accessed in many different ways, and is not restricted to a linear format. Comparative quantitative analysis using a control program shows consistently better student retention of information presented within the program that features concept maps. Qualitative results indicate that students find the conceptually-arranged knowledge base implicitly easy to understand, "fun" to use, and interesting to explore. Educational theory suggests that the success of such a format may be related to the schematic nature of memory. PMID- 1739885 TI - X. PMID- 1739886 TI - Noviceware: a model for learning the software development process. AB - Students and nursing faculty without formal computer science training can collaborate within an independent study structure to assist the student in gaining experience with the fundamentals of software development. The systems development life cycle approach provides an essential map to structure such independent studies. This article describes the development within an academic setting of a computerized research management system. The software builds a database of research case demographic data and data from a 65-item tool used in scoring videotapes of caregiver-infant interactions. For students and faculty contemplating similar projects, recommendations about planning software development experiences and securing hardware, software, and expert resources are provided. PMID- 1739887 TI - Implementing a computer system: issues for nurse administrators. AB - Because more and more health care agencies are becoming computerized, nursing administrators need to increase their knowledge about computer systems. Specifically, they must have at least some basic knowledge regarding the purchase, implementation, and maintenance of systems, because they and their staff are ultimately affected by them. This article describes how one agency managed the implementation of a new computer system and the issues that the nurse administrator faced during this process. PMID- 1739888 TI - Aortoenteric fistula 24 years after aortic endarterectomy. AB - Aortoenteric fistula is a well-recognized and potentially catastrophic complication of aortic surgery. It usually follows aortic graft placement and removal of the prosthesis. Extra-anatomic bypass is the treatment generally recommended. The authors report the case of a 74-year-old woman who presented with an aortoenteric fistula 24 years after aortic endarterectomy. The fistula was managed with an anatomically placed Dacron graft. The radiologic findings and approach to management of this uncommon problem are discussed. PMID- 1739889 TI - Spontaneous gastric decompression of pancreatic pseudocyst. AB - Spontaneous resolution of pancreatic pseudocysts is being reported with increasing frequency. Although many mechanisms have been proposed one that is not frequently recognized is spontaneous decompression into the gastrointestinal tract. This case report demonstrates the mechanism of spontaneous resolution of a traumatic pancreatic pseudocyst, several weeks after injury, through fistulization between the pseudocyst and the stomach. Spontaneous resolution of a pancreatic pseudocyst after a transient episode of diarrhea should suggest the mechanism of gastrointestinal decompression of the pseudocyst. PMID- 1739890 TI - The surgeon's dilemma: fibrocystic "dis" "ease" of the breast. PMID- 1739891 TI - Retention sutures: are they really necessary? PMID- 1739892 TI - Gauze roll padding for retention sutures. PMID- 1739893 TI - Field triage--help or hindrance? AB - Field triage protocols have potential benefits in urban trauma systems, but for optimal effect they must be tailored to local needs and tested in each system for sensitivity and specificity. They should be implemented only by experienced physicians and surgeons who can monitor and adjust the protocol when necessary. PMID- 1739894 TI - Air versus land transport of the critically injured patient. AB - Trauma patients frequently require transport from the hospital to which they are admitted initially to a trauma unit for further assessment and management. Canada's geography and demography provide unique challenges when transporting the severely injured patient by air or land. The author describes and compares air and land transport for the trauma patient. These complementary modes of transport are an integral part of a comprehensive trauma system. PMID- 1739895 TI - Airway management in the blunt trauma patient: how important is the cervical spine? AB - Emergency airway management in the patient with blunt trauma is a clinical dilemma. Many of these patients require immediate airway management, but each method carries its own set of risks and benefits. At the heart of the issue is the long-standing belief that oral intubation is hazardous in the presence of an unstable injury to the cervical spine. In this article, the issues surrounding selection of an appropriate technique for airway management are reviewed critically. Recommendations are made for management of the airway in this high risk group of patients with injury to the cervical spine. PMID- 1739896 TI - Small-volume resuscitation. AB - Small-volume resuscitation with hypertonic saline is an attractive modality but is still at an early stage of experimental and clinical investigation. Aggressive resuscitation from traumatic, hypovolemic shock could be facilitated during the prehospital phase, but hypotension remains a physiological and beneficial compensatory mechanism to minimize active bleeding until definitive care is provided. Despite encouraging results, the author concludes that, at present, hypertonic saline cannot be considered a truly "magic potion" for resuscitation of the trauma patient. PMID- 1739897 TI - Traumatic intracranial mass lesions: how soon for evacuation? AB - The purpose of this paper is to identify, by simple clinical parameters, those patients who are at particular risk for traumatic intracranial hematomas following accidental injury and to review the effects of delays in treatment on death from head injury. The findings indicate that vehicle occupants 30 years of age or younger are significantly (p less than 0.001) more likely to suffer from a "diffuse" head injury and serious truncal injury than they are to suffer a traumatic intracranial mass lesion. Conversely, older patients (60 years of age or older) injured in falls are more likely to have operable intracranial mass lesions without significant injury to the torso (p less than 0.001). Recommendations concerning early diagnosis and treatment of accident victims are made from these data. PMID- 1739898 TI - Age-related breast diagnosis. AB - Of the three commonest symptoms found in 3294 patients referred to a specialty breast clinic--mass, nodularity and pain--only nodularity was age related. Only 30% of the patients had a clinically localized abnormality, and only 19% of these abnormalities were suggestive of carcinoma. The majority of suggestive lesions were in women over 55 years of age. Of the patients seen because of a breast lump, 46% were found to have a significant mass. Most abnormalities were found in patients presenting with a mass or nipple discharge, and the significance was age related. Symptoms associated with the lowest rate of positive biopsies were nodularity, pain and skin or nipple changes. The biopsy and cancer rates were significantly age related. The cancer rate in women 40 years of age and under was 0.8%, between 41 and 55 the rate was 5%, and in those over 55 it was 21%. The predominant finding in young women was a fibroadenoma. In the middle age range fibrocystic change was most common, and in postmenopausal women most of the lesions were malignant. PMID- 1739899 TI - Tisseel in hypospadias repair. AB - Tisseel (Immuno AG, Vienna, Austria), a fibrin sealant, adhesive and hemostatic agent made up of sterilized human and bovine components, was used in hypospadias repairs. The incidence of fistula and significant edema and the duration of hospitalization were all reduced in 30 patients who underwent modified Mustarde repairs in which Tisseel was used when compared with a matched group of 30 repairs without Tisseel. In addition, the rate of complications in fistula repairs and complex revisions was reduced when Tisseel was used on urethral suture lines and under all skin flaps. PMID- 1739900 TI - [Heart-skin syndrome and cardiac myxoma: presentation of a case and clinical experience of 17 years]. AB - Between 1971 and 1988, cardiac myxoma was identified in 13 (0.003%) of 4000 patients who underwent open-heart surgery at the hopital du Sacre-Coeur in Montreal. One patient with multiple right atrial tumours also had abnormal cutaneous pigmentation compatible with the recently identified syndrome of "Carney's complex." This syndrome has also been associated with endocrine abnormalities such as primary nodular adrenal hyperplasia, with or without Cushing's syndrome. The authors review the literature and compare the findings with their experience in the surgical treatment of cardiac myxomas. PMID- 1739901 TI - Hemodynamic and temperature changes after aortocoronary bypass grafting. AB - Perioperative hemodynamic and temperature changes were reviewed in 58 patients who underwent aortocoronary bypass grafting. Core temperature showed an immediate decline postoperatively, secondary to core temperature cooling during bypass. Subsequent rewarming occurred over the next 8 to 12 hours, with the temperature often increasing above normal. The reason for this pyrexial response is discussed. The cardiac index was depressed immediately postoperatively, again with substantial recovery within 8 hours. This improvement over time occurred not only because of recovery of intrinsic function but also because of reduction in myocardial work due to falling systemic vascular resistance. The latter was high immediately postoperatively and then consistently fell during the rewarming phase. During the first 8 hours postoperatively there were significant changes in temperature and cardiac and systemic vascular resistance indices. The hemodynamic data correlated strongly with changes in temperature. Falling systemic vascular resistance required the institution of alpha-agonist therapy in 25% of patients. PMID- 1739902 TI - Subendocardial abscess as a complication of prolonged central venous access for parenteral nutrition. AB - Patients with chronic gastrointestinal diseases may require long-term parenteral nutrition. The authors describe a case in which a subendocardial abscess developed in the right atrium in association with staphylococcal septicemia. The patient, a 15-year-old boy, had a malpositioned Silastic catheter, the tip of which was in his right atrium. Staphylococcal abscess of the heart has been described previously after cardiac surgery, but the authors believe this is the first reported case related to a central venous catheter. PMID- 1739903 TI - Surgical management of perforated benign gastric ulcer in high-risk patients. AB - The authors compared the outcome in 40 high-risk patients who had a perforated benign gastric ulcer with respect to management by omental patch closure (OPC) or partial gastrectomy (PG). The patients were considered to be at high risk because of the presence of one or more of the following factors: age more than 70 years; initial hypotension; delay from presentation to operation of more than 12 hours; and significant premorbid illness. OPC was performed in 22 patients and PG in 10; the other 8 patients were initially managed nonoperatively (NonOp). Death rates were 40% overall--36% for patients in the OPC group, 30% for those in the PG group and 63% for those in the NonOp group. The hospital stay was more than 12 days for 57% of the OPC group, 86% of the PG group and 67% of the NonOp group. Sixty-eight percent of patients in the OPC group, 90% in the PG group and 89% in the NonOp group had complications. There was no significant difference in death rates between those treated with OPC and PG. There was a trend to lower death rates in patients over 70 years of age who underwent PG (1 of 6) compared with those who underwent OPC (7 of 12). The authors concluded that partial gastrectomy, a definitive surgical treatment for gastric ulcer disease, is not contraindicated in high-risk patients who have a perforated benign gastric ulcer. PMID- 1739904 TI - Causes of oral tongue cancer treatment failures. Analysis of autopsy cases. AB - Eighty-three autopsy cases of squamous cell carcinoma of the oral tongue were reviewed to identify retrospectively the causes of treatment failure. The cure rate for the primary cancers at autopsy was 48.2% (40 of 83). Regional lymph node metastases were found in 71.1% (59 of 83). Regional metastases and/or juxtaprimary recurrence frequently spread continuously and diffusely, forming bulky neck tumors in 38.6% (32 of 83). The incidence of distant lymph node metastasis (below the clavicle) and hematogenous metastasis was 35.4% (29 of 82) and 58.5% (48 of 82), respectively. The lung was the most common site of hematogenous metastases (52.4%, 43 of 82). Hematogenous metastasis occurred more frequently in the younger age group (less than 40 years of age; P = 0.03). Distant lymph node metastases were identified in the lung hilar, bifurcation, and paratracheal nodes in 89.7% (26 of 29) and had a statistically significant association with lung hematogenous metastasis. Univariate analysis revealed that gross appearance, tumor stage, clinical stage, presence of cervical lymph node metastasis, and interval from N0 to NX were significant predictors of survival time (duration from initial treatment to death). Rupture of the neck vessels was fatal in eight patients (9.6%), and hypercalcemia was seen in six (7.2%). Pulmonary infection was the direct cause of death in 33.7% of patients (28 of 83). Secondary malignant lesions occurred in 22.9% (19 of 83). PMID- 1739905 TI - Histopathologic characteristics of early stage esophageal carcinoma. A comparative study with gastric carcinoma. AB - Unlike the stomach, the esophageal mucosal layer has abundant vessels. To study the histopathologic character of cancer of the esophagus in comparison with that of stomach, the histologic findings (such as vascular or lymphatic permeation and lymph nodal involvement of cancer) were surveyed in 52 lesions of superficial esophageal carcinoma in which carcinoma invasion was limited to the submucosal layer, 448 cases of so-called early gastric carcinoma in which the carcinoma invasion was limited to the submucosal layer, and 109 cases of gastric carcinoma invading the proper muscle layer (PM-carcinoma). With respect to lymph node metastasis and lymphatic and vascular permeation, there was a particularly high incidence of carcinoma extending to the submucosal layer (SM-carcinoma) of the esophagus and a similar high incidence of PM-carcinoma of the stomach. Carcinoma limited to the mucosal epithelium and mucosal layer of the esophagus (MM carcinoma) has an incidence similar to carcinoma in the mucous membrane and SM carcinoma of the stomach, respectively. Thus, the cases in which carcinoma invasion was limited to the muscle layer of the mucosa of the esophagus were shown to have a prognosis similar to that of so-called early carcinoma of the stomach. PMID- 1739906 TI - Serial histologic investigation of squamous epithelial dysplasia associated with carcinoma of the esophagus. AB - Esophageal dysplasia and carcinoma were reviewed in the surgical specimens obtained from 37 patients with squamous cell carcinoma and 4 with adenocarcinoma; special attention was paid to the continuity of both lesions. Two hundred forty dysplasias and 113 carcinomas in situ (CIS) were recognized in the squamous cell carcinoma cases and 2 dysplasias and no CIS in the adenocarcinoma cases. The CIS often was accompanied continuously by severe dysplasia rather than mild or moderate dysplasia, suggesting some relationship between the CIS and the severity of dysplasia. However, many dysplastic lesions were located separately from the carcinoma. The frequency of appearance of the dysplasia near the CIS was low (11%), demonstrating a negative dysplasia-CIS sequence in many of the esophageal cancers. Lymphocytic infiltration was investigated further beneath the dysplasia or CIS. The degree of lymphocytic infiltration with lymphoid follicles correlated with the severity of dysplasia and was the highest in CIS. PMID- 1739907 TI - Low-dose rate telecobalt therapy as a boost against esophageal carcinomas. AB - The results of treating 54 esophageal carcinomas with low-dose rate telecobalt therapy (LDRT) as a boost were compared with those of treating 97 esophageal carcinomas with conventionally fractionated irradiation alone (CFI). The LDRT (100 cGy/hr, 500 to 700 cGy/day, a total dose of 1400 to 2000 cGy) was boosted at 10 days after 6000 cGy of the CFI dose. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rates in the former group were slightly better than in the latter group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose administered to this group was less than 8000 cGy. Using LDRT as a boost against esophageal carcinomas was found to be satisfactory therapeutically. PMID- 1739908 TI - HLA-DR antigen expression in intestinal-type and diffuse-type gastric carcinoma. AB - The expression of the HLA-DR antigen, a Class II HLA antigen, was analyzed in 41 cases of gastric carcinoma (23 intestinal-type and 18 diffuse-type according to a modified Lauren classification) using a monoclonal antibody that is reactive to this antigen in routinely formalin-fixed, paraffin-embedded tissue sections. Seventeen cases of intestinal-type gastric carcinoma and two cases of diffuse type gastric carcinoma were positive for the HLA-DR antigen. The staining in intestinal-type carcinoma generally was stronger and more extensive than in diffuse-type carcinoma, which showed only weak and focal staining. The difference in the frequency and pattern of staining between intestinal and diffuse-type gastric carcinoma supports the concept that these are two distinct subtypes of gastric carcinoma. PMID- 1739909 TI - Hereditary nonpolyposis colorectal cancer (Lynch syndrome II). Diploid malignancies with prolonged survival. AB - DNA flow cytometry was performed on 44 paraffin blocks from 16 specimens of 11 lesions in five patients from two families identified as probably having the dominant gene of the Lynch Type II syndrome. All but one specimen showed diploidy, although two such specimens were metastases and one a recurrence. The one aneuploid gastric biopsy was followed by a resection with diploidy in all 13 blocks from the malignancy and may represent a superficial change without clinical significance. The prolonged survival after discovery of malignancy in such families may be explained in part by diploidy of the lesions. PMID- 1739910 TI - High incidence of ras gene mutation in intrahepatic cholangiocarcinoma. AB - The DNA sequences around codons 12, 13, and 61 of the ras gene were analyzed by polymerase chain reaction and direct sequencing in 18 intrahepatic cholangiocarcinomas. The ras gene mutations were found in 9 of 18 (50%): 6 in K ras codon 12, 1 in K-ras codon 13, 1 in K-ras codon 61, and 1 in N-ras codon 12. The incidence of mutations was higher in the hilar type of intrahepatic cholangiocarcinomas, especially when these tumors were large. The incidence and spectrum of the mutations were almost the same as those reported in colon cancers, possibly indicating similar etiologic agent(s) in the carcinogenesis of both cancers. PMID- 1739911 TI - Lymphoma in inflammatory bowel disease. AB - Nine patients with lymphoma occurring in association with inflammatory bowel disease were admitted to The Mount Sinai Hospital between 1960 and 1983. Five (two men and three women) occurred among 1156 patients (0.43%) with ulcerative colitis (UC) and four (men), among 1480 patients (0.27%) with Crohn's disease (CD), a strong male preponderance in the latter group. In all four of the patients with CD and in four of the five patients with UC, the lymphomas were extraintestinal. The mean age of onset of UC in these patients was late (46 years, 19 years older than in our overall series), with lymphomas occurring a mean of only 12 years later. By contrast, patients with CD had bowel disease much younger (mean age, 26 years), and their lymphomas appeared after a longer disease duration (mean, 24 years). The risk factors for the one patient with colonic lymphoma were similar to those with colitis-associated colorectal carcinoma: extensive and long-standing colitis and relatively young age when malignant disease developed. Four of the patients with lymphoma had associated colonic carcinoma; in three of them, the carcinoma appeared within the first decade of colitis, an unusual occurrence. A second malignant lesion also occurred in three patients with UC. PMID- 1739912 TI - Primary biphasic lymphoplasmacytic lymphoma of the lung. A mucosa-associated lymphoid tissue lymphoma with compartmentalization of plasma cells in the lung and lymph nodes. AB - A primary mucosa-associated lymphoid tissue lymphoma of the lung in a 27-year-old man was found. The tumor was composed mainly of centrocyte-like cells and plasma cells. These two components were demarcated sharply from each other, resulting in a zoning or biphasic pattern. This characteristic pattern also was present in the involved regional lymph nodes. Monoclonality of tumor cells was shown immunohistochemically and by in situ hybridization techniques. This article also highlights the use of in situ hybridization in detecting light chain mRNA in paraffin sections. PMID- 1739913 TI - T-cell chronic lymphocytic leukemia. T-cell function and lymphokine secretion. AB - The leukemic T-cells of the six patients with T-cell chronic lymphocytic leukemia (T-CLL), four with CD4 and CD45R-positive (CD4+ CD45R*) T-CLL and two with CD8 and CD45R-positive (CD8+ CD45R+) T-CLL phenotype were studied for detailed immunologic phenotypic and functional characteristics. The levels of soluble interleukin-2 receptors were elevated significantly in the serum of all four patients with CD4+ CD45R+ T-CLL. Moreover, the CD4+ CD45R+ T-CLL patients' T cells, after in vitro stimulation with phytohemagglutinin and concanavalin A, expressed elevated percentages of interleukin-2 receptors on cells and secreted high interleukin-2 activity. The B-cell growth factor (BCGF) activity from three patients with CD4+ CD45R+ T-CLL was enhanced, but B-cell differentiation factor (BCDF) activity of the all T-CLL patients was decreased. Reduced BCGF and BCDF activity of the leukemic T-cells was one possible mechanism of hypogammaglobulinemia detected in two patients with T-CLL. All T-CLL patients' leukemic T-cells had diminished immunoregulatory functional activity in allogeneic mixed lymphocyte reactions. These observations suggest that leukemic T cells from T-CLL patients have many immunologic functional defects that may be important in their proliferative potential. PMID- 1739914 TI - Skin melanoma of the head and neck. Prognostic factors and recurrence-free survival in 512 patients. AB - The clinicopathologic and therapeutic data of 512 patients, with clinical Stage I invasive head and neck melanoma of the skin were retrospectively evaluated. There were 287 females and 225 males. Median age at primary surgery was 65 years (range, 18 to 96 years). Median observation period was 5 years (range, 1 month to 25 years). Site of first recurrence was local in 7% (38 of 512), regional in 13% (67 of 512) and distant in 6% (31 of 512). Sex, age, ulcerated tumor, and tumor thickness were found to act as independent risk factors to recurrence-free survival by Cox multivariate regression analysis. In addition, size of excision margin was found to be of no significance to survival without relapse when adjusting for the independent risk factors. PMID- 1739915 TI - Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma. AB - The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients. PMID- 1739916 TI - Expression of cell adhesion molecules in human melanoma cell lines and their role in cytotoxicity mediated by tumor-infiltrating lymphocytes. AB - The role of cell adhesion molecules (CAM) LFA1, ICAM-1, LFA3, VLA1, VLA4, CD29, CD44, and CD56 in tumor-infiltrating lymphocyte (TIL) and natural killer cell (NK)-mediated killing of target cells was studied. Melanoma cell lines and autologous TIL were derived from seven patients with metastatic melanoma, and cytotoxicity assays were done in the presence and absence of monoclonal antibodies (MoAb) to CAM expressed on melanoma cells or TIL. The melanoma cell lines analyzed were all positive for CD29 and LFA3 expression, negative for LFA1 expression, but showed variable expression of ICAM-1, VLA1, VLA4, CD44, and CD56. The effects of anti-CAM antibodies on TIL-mediated melanoma killing fell into three categories: (1) consistent inhibition of TIL-mediated killing was observed when melanoma cells were pretreated with anti-ICAM1 and anti-LFA-3 MoAb or when TIL were pretreated with anti-LFA1; (2) no effect was observed when melanoma cells were pretreated with anti-CD56; or (3) a discreet, but significant, inhibition was observed when target cells were pretreated with anti-CD29, anti VLA1, anti-VLA4, and anti-CD44. Cytotoxicity was significantly enhanced by pretreatment of target cells with gamma-interferon (gamma-IFN), although gamma IFN did not augment surface expression of the CAM studied. The NK-mediated killing of K562 cells was blocked by anti-LFA1, anti-CD18, and anti-ICAM, and partially inhibited by anti-CD44 MoAb. Together, these results suggest that several accessory CAM may play a role in regulating cellular cytotoxicity. Because cytotoxicity generally correlated with the level of expression of CAM in melanoma cells, weak CAM surface expression may provide a means for melanomas to escape immune surveillance. PMID- 1739917 TI - Estrogen receptor immunohistochemistry in carcinoma in situ of the breast. AB - Although estrogen receptor (ER) content and its clinical significance have been extensively evaluated in invasive breast cancer, ER expression in carcinoma in situ (CIS) of the breast and its correlates are less well understood. Thus, using an indirect immunoperoxidase technique and paraffin-embedded tissue, the authors studied ER expression in 100 breast tumors containing CIS with or without invasive carcinoma. The percentages of positive and of strongly positive nuclei were compared among histologic categories of CIS and between CIS and invasive carcinoma. The relationships between histologic features of CIS (cell size, nuclear pleomorphism, necrosis, extent of CIS) the patient's age, and the ER status of CIS also were evaluated. ER expression in pure CIS was compared with that of CIS with adjacent invasive carcinoma. Significant differences were observed between comedo CIS, which was frequently ER negative, and non-comedo and lobular CIS, which usually were positive. A predominance of large cells, independently from other features, was the best morphologic predictor of ER negative status in CIS. ER in CIS correlated with ER in invasive carcinoma in 98% of cases (r2 = 0.677). CIS without invasive carcinoma was more frequently ER weak or negative than CIS associated with invasive carcinoma. There was no difference in the overall percentage of nuclear staining in CIS of women of premenopausal versus postmenopausal age; however, a higher proportion of strongly positive cells occurred in the postmenopausal group. The authors conclude that the ER expression in CIS correlates with pathologic features of differentiation and is similar to that of invasive carcinoma. PMID- 1739918 TI - Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium. AB - To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells. PMID- 1739919 TI - Augmenting effect of sizofiran on the immunofunction of regional lymph nodes in cervical cancer. AB - The immunomodulating effect of sizofiran on regional lymph nodes (RLN) was studied in cervical cancer and benign gynecologic tumors comparatively between treated patients (sizofiran intramuscularly (1) 1 day (20 mg) before and (2) 8 days (20 mg) and 1 day (20 mg) before surgery; n = 34) and untreated patients (n = 21). The RLN (internal iliac lymph nodes) were dissected surgically, and freshly obtained mononuclear (MN) cells were studied to observe interleukin-2 (IL 2) production and lymphokine-activated killer cell and natural-killer cell activities. The infiltration of surface phenotype of MN cells into RLN was determined semiquantitatively by immunohistochemistry. Sizofiran augmented IL-2 production of RLN, which was accompanied by a marked increase in the number of cells stained with anti-Leu-3a and IL-2 receptor. This effect was found more often in Stage Ib disease than in Stage 0, and it was not observed in benign tumors. These results suggest that stimulation with some antigens (e.g., cancer antigen in the current study) is necessary to induce immunoaugmentation by sizofiran which has no antigenicity. The augmenting effect was seen even in lymph nodes involved by advanced cervical cancer. Therefore, sizofiran was found to be a potent biologic response modifier in patients with cervical cancer. PMID- 1739920 TI - Abrogation of the invasion of human bladder tumor cells by using protease inhibitor(s). AB - It was shown previously that invasive human transitional cell carcinoma cell line EJ, but not the noninvasive RT4 cells, can degrade basement membrane laminin and that the degradation of basement membrane laminin was a result of a redistribution of activated cysteine proteinase cathepsin B to the plasma membrane of the invasive EJ cells. Using a modified Boyden chamber and an artificial basement membrane, it was found first that cysteine proteinase inhibitor E-64 can abolish the ability of the EJ cells to invade through the artificial basement membrane to the underside of the filter. Second, E-64 can prevent the degradation of purified human basement membrane laminin by the plasma membrane fraction of invasive EJ cells. Third, E-64 does not affect the ability of the EJ cells to attach to the extracellular matrix nor is the inhibitory dose toxic to the cells when assayed with trypan-blue dye exclusion. However, E-64 does affect the ability of the EJ cells to respond to autocrine motility factor induced motility. Finally, in an in vivo model, E-64 was not toxic to the animals tested and may have limited the blood-borne metastatic ability of invasive EJ cells in the treated animals. It was concluded that proteinase cathepsin B may be involved in human bladder tumor invasion, in both extracellular matrix degradation and factor-induced cellular motility, and the authors suggested that the use of inhibitor(s) to cysteine proteinases may limit the invasive potential of human bladder cancer cells. PMID- 1739921 TI - Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases. AB - A multivariate analysis was carried out in 492 patients with metastatic neck disease from squamous cell carcinoma to determine the influence of clinical and therapeutic factors on survival, local and regional control, and distant metastases. After radiation treatment with radical intent, recurrence at the primary site was the most frequent site of treatment failure (20% of cases), followed by distant metastases (14% of the cases), whereas isolated neck recurrences occurred in only 7% of the patients. The most significant factors influencing survival were primary tumor site, node fixation, N-stage, T-stage, and number of lymphatic chains. The most significant factors influencing local control were primary site, T-stage, and node fixation. Significant factors influencing regional control were radiation therapy volume, primary tumor site, node fixation, and node location (upper and lower neck). Significant factors influencing distant control were N-stage, number of nodes, and number of involved lymphatic chains. PMID- 1739922 TI - Coronary artery disease mortality in patients treated for Hodgkin's disease. AB - The authors conducted a follow-up study of the association between mediastinal irradiation, chemotherapy, and mortality from coronary artery disease in 4665 patients treated for Hodgkin's disease. Study subjects were followed after the diagnosis of Hodgkin's disease until death or the closing date of the study. The average duration of follow-up was 7 years; 2415 patients died, and 124 cases of coronary artery disease were identified from death certificates, including 68 cases of acute myocardial infarction. The age-adjusted relative risks (RR) of death with any coronary artery disease after mediastinal irradiation and after chemotherapy were 1.87 (95% confidence interval [CI], 0.92 to 3.80) and 1.28 (CI, 0.77 to 2.15), respectively. A significantly increased risk of death in the subcategory myocardial infarction was observed after mediastinal irradiation (RR, 2.56; CI, 1.11 to 5.93) but not after chemotherapy (RR, 0.97; CI, 0.53 to 1.77). These results support the hypothesis that radiation therapy to the mediastinum increases the risk of coronary artery disease. PMID- 1739923 TI - Blood eosinophilia in Hodgkin's disease. A follow-up of 25 cases in Venezuela. AB - Twenty-five patients with Hodgkin's disease and high eosinophil counts were observed for an average of 90 months. Fluctuations in the levels of eosinophils were important in the course of observation. No relation with stages, histologic type, or evolution was noticed. Steroid-containing regimens and severe premortem conditions seemed to lower the counts. Relapse-free survival was shorter in our 25 patients than in a control group of 50 patients with Hodgkin's disease and no eosinophilia who had approximately the same stage, histologic type, and treatment of disease. However, the overall survival was somewhat better for the eosinophilic patients with stages IIIB and IV (0.1 greater than P greater than 0.05). PMID- 1739924 TI - Hodgkin's disease and non-Hodgkin's lymphoma containing Reed-Sternberg-like giant cells in Taiwan. A clinicopathologic analysis of 50 cases. AB - Hodgkin's disease (HD) is uncommon in Taiwan. In reviewing the clinicopathologic features of 50 cases, the authors found that the diagnosis of HD was complicated with non-Hodgkin's lymphoma (NHL). Fourteen cases were reclassified as NHL containing Reed-Sternberg (RS) giant cells, mostly peripheral T-cell lymphoma (PTL), and 34 cases as classic HD, which included 8 cases of lymphocyte predominance, 10 of nodular sclerosis, 12 of mixed cellularity, and 4 of lymphocyte depletion. For cases of HD, there was a bimodal age-incidence distribution with peaks at the third and fifth decades; 61.8% manifested Stage B symptoms and 80.6% had Stage III/IV disease. The group of patients with NHL, compared with those with classic HD, was found to be older (mean age, 41.4 years versus 33.1 years; P less than 0.05), to have more extranodal disease (35.7% versus 8.8%, P less than 0.05), less complete remission rate (25% versus 67.9%, P less than 0.05), and shorter median survival (29 months versus 90 months). Most of the NHL patients originally were diagnosed as having atypical or unclassified HD. Thus, the authors conclude that the previous observation of a predominance of mixed cellularity HD in Asian regions may be attributable to the inclusion of PTL, which may mimic HD in histology. Because there is a marked difference in clinical behavior and prognosis, it is important to distinguish between HD and NHL containing RS giant cells in an area with a high incidence of PTL. PMID- 1739925 TI - Clinicopathologic and therapeutic aspects of angioimmunoblastic lymphadenopathy related lesions. AB - The clinicopathologic features of 14 patients with angioimmunoblastic lymphadenopathy (AIL)-related lesions were analyzed. Lymph node biopsy specimens from all the patients showed a diffuse obliteration of lymph node architecture, prominent vascular proliferation, a polymorphous cellular infiltrate, including immunoblasts, and varying degrees of clear cell proliferation. The patients were eight males and six females, with a median age of 58.5 years. All but one were in an advanced stage at the time of diagnosis. Bone marrow involvement was observed in eight patients. Thirteen patients had a negative serologic reaction for antibody to human T-cell leukemia virus type I (HTLV-I), and one patient was considered to be a HTLV-I carrier. Polyclonal hypergamma-globulinemia was observed in 6 patients, and 6 of the 12 patients showed elevated IgE levels. Immunophenotyping of the involved lymph nodes revealed a preponderance of T-cells in all the patients. Eleven of these patients showed a predominance of CD4+ over CD8+ T-cells, and only one patient showed a predominance of CD8+ over CD4+ T cells. Two of five patients whose gene analysis was carried out showed clonal rearrangement of the T-cell receptor beta chain gene without rearrangement of the immunoglobulin heavy chain genes. Twelve patients received doxorubicin-containing combination chemotherapy; of these, 7 patients achieved complete response, and the other 5 had partial response. Nine patients are still alive with a median follow-up period of 21 months, and five patients died during the follow-up period. Progression to high-grade T-cell lymphoma with systemic infiltration was ascertained in two of three cases for which autopsy was performed. From our experience, we recommend doxorubicin-containing combination chemotherapy as initial therapy for AIL-related lesions. PMID- 1739926 TI - Megestrol acetate in cancer anorexia and weight loss. AB - High-dose megestrol acetate has been associated with increased appetite and weight. To examine the effects of high-dose megestrol acetate in the treatment of anorexia and weight loss in patients with advanced hormone-insensitive malignant lesions, a randomized double-blind placebo-controlled trial was conducted. Patients receiving megestrol acetate for 1 month reported a significant improvement in appetite and adequacy of food intake compared with those receiving placebo. A three-item scale measuring appetite, adequacy of food intake, and concern about weight revealed a higher improvement with megestrol acetate than with placebo. Patients who worsened while receiving placebo had similar favorable changes after the cross over to megestrol acetate. These data indicate that megestrol acetate may improve appetite and food intake in patients with advanced cancer. PMID- 1739927 TI - Patterns and risks of cancer in farmers in Alberta. AB - Data on occupations and life styles of patients with cancer have been collected since 1983. To investigate cancer patterns and risks in farmers in Alberta, all farmers were abstracted and compared with nonfarmers in the data base, using case control analysis. Controls were patients with cancer at any site except the index site. Significantly elevated odds ratio (OR), adjusted for age and smoking, were found among the farmers for cancers of the lip (OR = 3.22, 95% confidence interval [CI] = 2.14 to 4.84) and prostate (OR = 1.31, 95% CI = 1.11 to 1.55). Crude risk for lung cancer was significantly lower in farmers, but statistical significance disappeared when risk was adjusted for smoking (OR = 0.81, 95% CI = 0.65 to 1.02). Farmers were at considerably lower risk of malignant melanoma of the skin, compared with nonfarmers (OR = 0.57, 95% CI = 0.36 to 0.91). PMID- 1739928 TI - Familial occurrence of infantile myofibromatosis. AB - Two brothers with multicentric infantile myofibromatosis (IM) are reported. In both, tumors were present at birth; the tumors regressed spontaneously, but new lesions developed throughout the follow-up periods of 15 and 8 years. Immunohistochemically, the nodules were found to be positive for vimentin and actin, but negative for desmin and S-100 protein; these findings support the myofibroblastic nature of IM. A literature review revealed nine additional families with IM in more than one family member. Although the occurrence of IM in eight sets of siblings, with consanguinity in two of them, favors an autosomal recessive mode of inheritance, the disorder also has been well documented in half sisters and in successive generations, which makes autosomal dominant inheritance a more plausible explanation. PMID- 1739929 TI - Childhood cancer registry of the Province of Torino, Italy. Survival, incidence, and mortality over 20 years. AB - Incident childhood cancers in the Province of Torino, Italy (population aged 0 to 14 years averaging 0.5 million) have been registered since 1967. Four population based exhaustive surveys have been done to collect cases diagnosed during the periods 1967 to 1969, 1970 to 1975, 1976 to 1981, and 1982 to 1986. For each registered child, vital status on June 30, 1988 was assessed. This article reports incidence, mortality, and survival rates over a 20-year period. A statistically significant trend toward an increased incidence of soft tissue sarcomas was identified. Statistically insignificant trends included an increased incidence of brain tumors (probably reflecting improved diagnostic procedures) and a decreased incidence of thyroid tumors. Incidence rates of leukemias in the first year of life tended to decrease. As expected, survival rates of some childhood cancers dramatically improved throughout the 20-year period; this occurred in leukemias, brain tumors, soft tissue sarcomas, and renal tumors. Survival rates are compared with observations in comparable population-based series. PMID- 1739930 TI - DNA content and other prognostic features in childhood medulloblastoma. Proposal of a scoring system. AB - The authors reviewed clinical features, surgical extent of resection, histologic parameters, and DNA content in 55 children with medulloblastomas and found that complete or near total resection, absence of tumor dissemination, tumor DNA aneuploidy, and low proliferative index correlated with a favorable clinical outcome. A scoring system was developed based upon these features to identify patients who, in the future, may benefit from more aggressive or novel therapeutic regimens. Patient age and sex and adjuvant chemotherapy did not significantly correlate with long-term survival. The data also suggest that tumors that have been designated as cerebellar neuroblastomas may be a distinct group of posterior fossa tumors, which may have a better prognosis. PMID- 1739931 TI - Home care of HIV/AIDS. PMID- 1739932 TI - The "new" profession. PMID- 1739933 TI - The Manitoba nurses' strike--win, lose or draw? PMID- 1739934 TI - Strikes by nurses. PMID- 1739936 TI - The right place. PMID- 1739935 TI - The power of self-help. PMID- 1739937 TI - Monitoring the path of nursing. PMID- 1739938 TI - Creating your own conceptual framework. PMID- 1739939 TI - Checking the fit. PMID- 1739940 TI - Political action. Choice or obligation? PMID- 1739941 TI - [Hospital at home, a reality]. PMID- 1739942 TI - [Education, key to successful integration]. PMID- 1739943 TI - Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. AB - Piperine is known to modify the biotransformation of drugs. The effect of piperine on the metabolic activation and distribution of [3H]-aflatoxin B1 (AFB1) in rats has been described. Piperine markedly inhibited liver microsome-catalysed [3H]AFB1 binding to calf thymus DNA in vitro, in a dose dependent manner. Rats pretreated with piperine accumulated considerable [3H]AFB1 radioactivity in plasma and in the tissues examined as compared to the controls. However, piperine had no influence on hepatic [3H]AFB1-DNA binding in vivo, which could possibly be due to the null effect of piperine on liver cytosolic glutathione (GSH) 5 transferase activity. Piperine-treated rat liver microsomes demonstrated a tendency to enhance [3H]AFB1 binding to calf thymus DNA in vivo. The effect of piperine on AFB1 metabolism thus closely resembles the mode of action of SKF 525 A on biotransformation of foreign compounds. PMID- 1739944 TI - Immunoquantitation of von Willebrand factor (factor VIII-related antigen) in vinyl chloride exposed workers. AB - Angiosarcoma of the liver is a rare malignant tumor which has been associated with occupational exposure to vinyl chloride (VC). We have determined by ELISA the level of von Willebrand factor (vWf) in the serums of 107 VC-exposed workers, active or retired, and of 133 blood donors used as controls. The vWf level was slightly but significantly higher in the VC-exposed group than in the control group (P = 0.035). Seventeen VC-exposed workers exhibited a raised level of vWf, with no biochemical sign of hepatic disturbance, nor any evidence of illness; only one of them exhibited elevated alkaline phosphatase and gamma-glutamyl transpeptidase values. The vWf serum level of 3 patients with hepatic angiosarcoma associated to VC-exposure was markedly elevated. These increased levels of vWf in VC-exposed workers most likely reflect an increased activity of liver endothelial cells; whether an elevated level of vWf could be associated with increased risk of developing liver angiosarcoma remains to be determined. PMID- 1739945 TI - Differences in metabolic activation of dibenzo[a,e]fluoranthene characterized by 32P-postlabeling in two mouse fibroblast models. AB - The formation of DNA adducts was investigated in mouse fibroblasts from two different tissues--embryos and adult lung--after incubation with dibenzo[a,e]fluoranthene (DBF) or its major proximate metabolites. The nuclease P1 modification of the 32P-postlabeling method was adapted for detection of DBF DNA adducts. Quantitative and qualitative differences were observed in the metabolic activation mediated by the two cell types. DBF-DNA adducts generated three major spots reproducibly, and more than ten spots of medium or weak importance. The highest level of DNA binding occurred via the DBF-bay region vicinal dihydrodiol epoxide but with significant differences in the quantitative distribution of adducts. Striking qualitative differences were observed when lung fibroblasts were incubated with the DBF-pseudo bay region dihydrodiol (DBF-12,13 DHD). The spots representing adducts induced in embryo fibroblasts by DBF-3OH 12,13-DHD, a further metabolite of DBF-12,13-DHD, were totally absent from chromatograms of lung cells. These results show that both embryo and lung fibroblasts can activate DBF but that different cytochrome P-450 forms and substrate affinities are involved. The finding that different activation systems may be present in subcategories of the same tissue, may provide a partial explanation for the wide variations in sensitivity to carcinogens among species, organs and tissues. PMID- 1739946 TI - Gamma-interferon and retinoic acid synergize in inhibiting the growth of human neuroblastoma cells in nude mice. AB - We have investigated the effects of retinoic acid (RA), human recombinant gamma interferon (gamma-IFN), and the association of both agents on the growth of human neuroblastoma (NB) cells in [CD1(nu/nu)] nude mice. Two human NB cell lines, namely LAN-5 and GI-LI-N, were previously adapted to grow in syngeneic animals for 7 consecutive passages. At the eighth passage, only animals which developed 10-mm diameter tumors within 40 days from xenograft were admitted to the study. RA and/or gamma-IFN were administered subcutaneously 3-5 days per week for 3 consecutive weeks. The number of days necessary for each tumor mass to grow up to 20 mm diameter (in vivo doubling time, ivDT) was then evaluated. Tumor growth was significantly inhibited in gamma-IFN (P less than 0.005) and RA (P less than 0.05) treated mice grafted with GI-LI-N. The combination of the two agents did not further enhance ivDT. The tumor growth inhibition was not statistically significant in LAN-5 bearing mice treated with RA or gamma-IFN alone, while a synergistic effect between the two drugs was observed (P less than 0.05). We conclude that parenteral combined administration of RA and gamma-IFN may prove to be useful in inhibiting the growth of tumors derived from human NB cells resistant to single inducers. PMID- 1739947 TI - Changes in alanine transport in plasma membrane vesicles from rat liver during the early stages of diethylnitrosamine-induced hepatocarcinogenesis. AB - The transport of L-alanine, a natural substrate of system A, across liver plasma membrane vesicle preparations was modified during the early stages of rat DENA hepatocarcinogenesis. Kinetic studies indicated an increase of the Vmax, with normal Km values, at 30 h in rats undergoing a partial hepatectomy. Normal Vmax and drastically reduced Km values were present using membrane preparations from liver tissue showing enzyme-altered hyperplastic foci and/or preneoplastic nodules. The results suggest that alanine transport is differently affected by initiating and promoting stimuli during rat DENA hepatocarcinogenesis. The changes of the Vmax could be related to the promoting effect of partial hepatectomy on cell proliferation whereas the changes of the affinity constant (Km) could be the result of intrinsic modifications of the transporter in initiated cells. PMID- 1739948 TI - The enzymatic activities of branched-chain amino acid catabolism in tumour bearing rats. AB - Rats bearing the Walker-256 carcinosarcoma showed significant changes in branched chain amino acid metabolism as compared with their non-tumour-bearing controls. In vitro measurement of branched-chain amino acid transaminase and branched-chain 2-oxo acid dehydrogenase showed significant increases in the skeletal muscle of tumour-bearing animals. In addition, the circulating concentration of leucine was increased in the tumour-bearing group. It can be concluded that the metabolism of branched-chain amino acids in the host is profoundly altered by the presence of a tumour and this may well be one of the main factors contributing to the so-called cancer cachexia. PMID- 1739949 TI - Cystatins and stefins in ascites fluid from ovarian carcinoma. AB - Cysteine proteinase inhibitors (CpI) of all three families were found in ascites fluid from patients with ovarian carcinoma. CPIs were isolated by affinity chromatography on carboxymethylated papain Sepharose, followed by gel filtration, anti-stefin-Sepharose and ion exchange chromatography. The highest apparent inhibition against cathepsin B (Cat B) was found in the low molecular mass (LMM) CPI fraction. Immunochemical analysis of this fraction revealed the presence of cystatin C and both stefins A and B while the high molecular mass (HMM) CPI fraction contained kininogens. We demonstrated that CPIs were not completely associated with cysteine proteinases (CPs): about 20% of HMM CPIs and 50% of LMM CPIs were free in native ascites fluid. Affinity chromatography on anti-Cat B Sepharose revealed that the major LMM CPI, associated with Cat B in native ascites fluid, was the full length form of cystatin C, pI 9.3, and not its truncated form, pI 7.85. The latter was isolated and found to inhibit Cat B in vitro with apparent Ki 0.18 +/- 0.2 nM. Stefin A was isolated from alkaline activated ascites fluid in its two isoforms, pI 4.6 and 4.9. In native ascites, the pI 4.9 isoform was mostly associated with Cat B. Ki for Cat B was 3.55 +/- 1.7 nM, not significantly different from the Ki values measured for stefin A, isolated from other human tissues and biological fluids. PMID- 1739950 TI - Monitoring of urinary excretion of modified nucleosides in cancer patients using a set of six monoclonal antibodies. AB - Monoclonal antibodies were produced and characterized in order to allow the monitoring of the urinary excretion of six modified nucleosides. The specificity of each antibody was determined and competitive solid-phase enzyme-linked immunoassays were designed, the sensitivity of which lay in the pmol range. Detection and quantitation of 5-methylcytidine (5-MeCyd), 4-acetylcytidine (4 AcCyd), 1-methylinosine (1-MeIno), 1-methyladenosine (1-MeAdo), 7-methylguanosine (7-MeGuo) and pseudouridine (psi-Urd) can be performed in small volumes (70 microliters) of untreated urine. Results can be obtained from as many as 20 different samples, for one molecule, within 3 h. With this technique, values observed for three commonly measured nucleosides in urine from healthy subjects (psi-Urd, 1-MeAdo and 1-MeIno) are in good agreement with those reported by other authors after analysis by high performance liquid chromatography. Results obtained in urine from cancer patients show significantly increased levels of the six haptens quantitated by this immunoassay. PMID- 1739951 TI - Fractionated treatment of CaD2 tumors in mice sensitized with aluminium phthlocyanine tetrasulfonate. AB - CaD2 mammary carcinomas transplanted into the feet of mice were treated with tetrasulfonated phthalocyanine (AlPcS4) and laser light at 680 nm. A light dose of 135 J/cm2 was either given as continuous radiation (15 min) or fractionated with 15 s exposure, 15 s darkness, 15 s exposure and so on for 30 min. The CaD2 tumors were found to respond better to a fractionated exposure than to the same energy given in one exposure. The reason for this is assumed to be a relocalization of the dye upon illumination, seen as a rapid decrease in fluorescence. When the laser light was turned off, the fluorescence returned to almost the initial value. PMID- 1739952 TI - The right ventricle. PMID- 1739953 TI - Anatomy and pathology of the right ventricle (including acquired tricuspid and pulmonic valve disease). AB - With the increased availability of various imaging techniques to assess right ventricular structure and function, there has been a greater appreciation of the importance of right ventricular performance in the setting of left ventricular dysfunction as well as intrinsic ventricular diseases. This article discusses the pathology of the right ventricle, tricuspid valve, and pulmonic valve and concentrates on the major acquired and congenital conditions that manifest in an adult population. PMID- 1739954 TI - The right ventricle in pulmonary disease. AB - Abnormal pulmonary function that causes pulmonary artery hypertension increases right ventricular work. To compensate, the right ventricle enlarges, and cor pulmonale develops. Right ventricular failure occurs when these adaptive mechanisms cannot compensate for the hemodynamic burden. The various pulmonary diseases that are associated with right ventricular overload and the physiologic responses of the right ventricle to increased afterload are discussed in this article. PMID- 1739955 TI - Endovascular infections arising from right-sided heart structures. AB - Endovascular infections that involve the right side of the heart present their own unique etiologies, pathophysiologies, clinical manifestations, and therapeutic issues. The pathology of the vegetations of right-sided endocarditis is identical to that of left-sided endocarditis. These vegetations are irregular, friable masses of varying size the contain platelets, fibrin, RBCs, and microorganisms. These lesions serve as a nidus for deep-seated infection and produce sustained bacteremia. Right-sided endocarditis occurs in 5% to 10% of all cases of endocarditis. The most common predisposing factors are IV drug abuse and congenital heart disease. S. aureus is the most common pathogen. The clinical manifestations include fever, chills, rigor, dyspnea, pleuritic pain, productive cough, and hemoptysis. The cardiac manifestations can be notably absent early in the course of the disease, with only 20% of patients initially showing a significant murmur on physical examination. Peripheral embolic lesions can be seen. Echocardiography is helpful in identifying vegetations on the tricuspid valve in a significant proportion of patients. The chest radiograph is characteristic, showing features typical of multiple septic pulmonary emboli. The radiograph shows multiple, small, fuzzy, patchy, peripherally located densities that can change rapidly on serial films. Complications of right-sided endocarditis include pulmonary infarction, pulmonary abscess, progressive right sided heart failure, and renal abnormalities. The treatment of right-sided endocarditis includes prolonged therapy, with high doses of IV bactericidal antibiotics. Four weeks of antibiotic therapy is generally required, but newer regimens using combination antibiotic therapy can be successful in sensitive strains of viridans group streptococci and S. aureus. Surgical resection of the tricuspid valve is recommended for organisms that do not respond to initial antibiotic therapy, fungal endocarditis, resistant relapsing organisms, or coexistent infection with S. aureus and P. aeruginosa. The prognosis of right sided endocarditis is generally favorable when compared with left-sided endocarditis. The prognosis is especially favorable in IV drug abusers infected with S. aureus. Patients infected with fungal organisms, Pseudomonas or Serratia, have a worse prognosis. The presence of significant right-sided heart failure also imparts a worse prognosis. PMID- 1739956 TI - Tachycardias of right ventricular origin. AB - Ventricular tachycardia arising from the right ventricle usually has a left bundle branch morphology and occurs in a variety of disorders. Uhl's anomaly and right ventricular dysplasia may represent a spectrum of one disorder and are a cause of right heart dilatation, failure, and premature sudden death due to ventricular arrhythmias. Familial forms of the disorder may account for focal clustering in some geographic areas. Management should involve aggressive stratification of arrhythmia risk and may include medical, surgical, or device therapy. In contrast, the syndrome of right ventricular outflow tract tachycardia, including nonischemic exercise-induced and repetitive monomorphic ventricular tachycardia, is a more benign entity. Management often involves beta- and calcium channel blocking drugs or type IC antiarrhythmic drugs. Catheter ablation of the arrhythmia focus in the right ventricular outflow tract has been used in selected patients. In this syndrome the right ventricle is normal, and noninvasive testing as well as electrophysiologic studies can be helpful in distinguishing it from the more malignant right ventricular dysplasia. Ventricular arrhythmias may also be seen after right ventricular incision, as in surgical repair of tetralogy of Fallot and ventricular septal defects. Significant ventricular ectopy associated with an abnormal right ventricle (enlarged or depressed systolic function) is associated with an increased risk for sustained arrhythmia and sudden cardiac death in this group. The optimal indicator(s) of highest risk in these patients remains under investigation but will likely include electrophysiologic testing. Bifascicular block occurs commonly after repair of tetralogy of Fallot, but is usually benign. Isolated right ventricular infarction is rare. Most right ventricular arrhythmias associated with ischemia occur in the setting of iatrogenic catheter manipulation for pacing or hemodynamic monitoring. In conclusion, right ventricular arrhythmias involve an unusual and interesting group of clinical entities and appear to span the spectrum of arrhythmias mechanisms. A macroreentrant activation ring around the ventriculotomy scar may account for the arrhythmias following repair of tetralogy of Fallot. Microreentry at sites of morphologic abnormalities results in the arrhythmias associated with right ventricular dysplasia and ischemia. Triggered activity related to DADs or, less likely, abnormal automaticity, produce repetitive monomorphic ventricular tachycardia and nonischemic exercise-induced ventricular tachycardia, both of which usually originate from the right ventricular outflow tract. Iatrogenic ventricular tachycardia associated with catheter manipulation is especially likely to occur in the presence of right ventricular ischemia and infarction. It is important to recognize these clinical entities because treatment is specific.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1739957 TI - The right ventricle in disorders causing pulmonary venous hypertension. AB - The right ventricle is frequently affected by pulmonary arterial hypertension of postcapillary obstructive origin. The disorders that cause states of pulmonary venous hypertension arise in the left ventricle, left atrium, or pulmonary veins. Biochemical factors, the pericardium, interventricular septum, and pulmonary arterial system combine to communicate the effects of these disorders to the right ventricle. Although not ideally suited to pressure loading, the right ventricle undergoes a series of structural and hemodynamic adaptations that allow for chronic compensation until failure supervenes, with characteristic clinical findings. Exercise may serve to magnify the abnormalities of right ventricular function. Correction of left-sided heart lesions with improvement in pulmonary venous hypertension is associated with favorable effects on the right ventricle. In states of left-sided heart failure, the level of right ventricular function may provide important prognostic information. PMID- 1739958 TI - Right ventricular assist devices and the surgical treatment of right ventricular failure. AB - Treatment of patients with severe right ventricular dysfunction follows a continuum of progressive therapies. If optimization of volume status and inotropic support do not adequately improve right ventricular function, higher levels of mechanical circulatory support are required. A right-sided intraaortic balloon pump has been helpful in such circumstances. The centrifugal pump and the artificial ventricle provide the most effective long-term circulatory support for patients with right ventricular or biventricular failure after cardiopulmonary bypass, myocardial infarctions, or as a bridge to cardiac transplantation. All of these support measures still carry a high morbidity and mortality. Survival in approximately one third of these high-risk patients can be expected with the use of right ventricular assist devices. Cardiopulmonary bypass has also been effective for circulatory support of patients with massive pulmonary emboli. PMID- 1739959 TI - Assessment of right ventricular function. Role of nuclear imaging techniques. AB - Due to the complex geometry of the right ventricle, contrast angiography is not ideally suited for determining its volumes and for carrying out volume-based analyses. Nuclear cardiological techniques, being free from this limitation, have played an important role in understanding the right ventricular performance in various disease conditions. This technique is currently in clinical use and can be applied for assessing the role of right ventricular function in various cardiopulmonary diseases. PMID- 1739960 TI - Hemodynamics of the right ventricle in normal and disease states. AB - The physiology and hemodynamic functions of the right ventricle in normal and disease states differ considerably from those of the left ventricle. To illuminate these differences, the right ventricle's essential functions in the normal circulation are reviewed, its functional anatomy and blood supply are described, principles and methods of systolic function assessment are discussed, and hemodynamic adaptations to selected diseases causing chronic right-side volume and pressure overload are highlighted. PMID- 1739961 TI - Right ventricular infarction. AB - Right ventricular myocardial infarction, long unrecognized because of a lack of diagnostic methods and unsupported beliefs regarding the dispensability of the right ventricle, may now be diagnosed using well-accepted criteria. Right ventricular infarction is clearly associated with anterior left ventricular infarction as well as inferior infarction. It may occur in 30% to 40% of patients with inferior infarction, although a much smaller percentage experience hemodynamic instability on the basis of right ventricular infarction. Pathophysiologically, right ventricular systolic and diastolic dysfunction are exacerbated by pericardial restraint and concomitant left ventricular dysfunction, accounting for the characteristic findings of cardiogenic shock and marked preload dependence in many patients. Right ventricular infarction may be suspected on the grounds of clinical presentation, physical examination, and enzymatic findings, and is confirmed using well-defined electrocardiographic, radionuclide, echocardiographic, and hemodynamic criteria. Once diagnosed, right ventricular infarction requires specific hemodynamic and pharmacologic management, including the judicious use of volume expansion and inotropic support. Several forms of mechanical and surgical intervention are of therapeutic value in treating hemodynamic disturbances and recognized complications. With appropriate management, the prognosis for patients with right ventricular infarction is generally favorable. PMID- 1739962 TI - Facts about the National Center for Nursing Research. PMID- 1739963 TI - More is better: activators and repressors from the same gene. PMID- 1739964 TI - Multiple extracellular activities in Drosophila egg perivitelline fluid are required for establishment of embryonic dorsal-ventral polarity. AB - Twelve maternal effect genes (the dorsal group and cactus) are required for the establishment of the embryonic dorsal-ventral axis in the Drosophila embryo. Embryonic dorsal-ventral polarity is defined within the perivitelline compartment surrounding the embryo by the ventral formation of a ligand for the Toll receptor. Here, by transplantation of perivitelline fluid we demonstrate the presence of three separate activities present in the perivitelline fluid that can restore dorsal-ventral polarity to mutant easter, snake, and spatzle embryos, respectively. These activities are not capable of defining the polarity of the dorsal-ventral axis; instead they restore structures according to the intrinsic dorsal-ventral polarity of the mutant embryos. They appear to be involved in the ventral formation of a ligand for the Toll protein. This process requires serine proteolytic activity; the injection of serine protease inhibitors into the perivitelline space of wild-type embryos results in the formation of dorsalized embryos. PMID- 1739965 TI - The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin responsive adenylyl cyclase. AB - Four putative adenylyl cyclase genes from Drosophila melanogaster were identified by virtue of their extensive sequence homology with mammalian cyclases. One corresponds to the learning and memory gene rutabaga and is most similar to the mammalian brain Ca2+/calmodulin (CaM)-responsive cyclase. In a mammalian expression system, rutabaga cyclase activity was stimulated approximately 5-fold by the presence of Ca2+/CaM. A point mutation, identified at this locus in rut1 mutant flies, resulted in loss of detectable adenylyl cyclase activity. New P element insertion-induced rutabaga mutations mapped to within 200 nucleotides of the 5' end of the rutabaga cDNA. These data confirm the identity of the rutabaga locus as the structural gene for the Ca2+/CaM-responsive adenylyl cyclase and show that the inactivation of this cyclase leads to a learning and memory defect. PMID- 1739966 TI - L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein. AB - The intracellular pathogenic bacterium L. monocytogenes can spread directly from cell to cell without leaving the cytoplasm. The mechanism of this movement, generated through bacterially induced actin polymerization, is not understood. By analyzing an avirulent Tn917-lac mutant defective for actin polymerization, we have identified a bacterial component involved in this process. The transposon had inserted in actA, the second gene of an operon. Gene disruption of downstream genes and transformation of the mutant strain with actA showed that the actA gene encodes a surface protein necessary for bacterially induced actin assembly. Our results indicate that it is a 610 amino acid protein with an apparent molecular weight of 90 kd. PMID- 1739967 TI - The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. AB - We report the first intracellular characterization of an endogenous nontransmembrane protein tyrosine phosphatase (PTP). Using affinity-purified polyclonal antibodies, we have identified PTP-1B as a 50 kd serine phosphoprotein in immunoprecipitation and immunoblotting assays. Surprisingly, indirect immunofluorescence experiments indicate that PTP-1B is localized predominantly in the endoplasmic reticulum (ER). Subcellular fractionation is consistent with this localization and establishes that PTP-1B is tightly associated with microsomal membranes, with its phosphatase domain oriented towards the cytoplasm. The C terminal 35 amino acids of PTP-1B are both necessary and sufficient for targeting to the ER. The finding of a tyrosine phosphatase on the ER suggests new possibilities for cellular events controlled by tyrosine phosphorylation. PMID- 1739968 TI - Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene specific translational control of GCN4 in yeast. AB - We show that phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) by the protein kinase GCN2 mediates translational control of the yeast transcriptional activator GCN4. In vitro, GCN2 specifically phosphorylates the alpha subunit of rabbit or yeast eIF-2. In vivo, phosphorylation of eIF-2 alpha increases in response to amino acid starvation, which is dependent on GCN2. Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2 alpha by GCN2 in vivo and in vitro and abolishes increased expression of GCN4 and amino acid biosynthetic genes under its control in amino acid-starved cells. The Asp-51 substitution mimics the phosphorylated state and derepresses GCN4 in the absence of GCN2. Thus, an established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast. PMID- 1739969 TI - Short peptide domains target proteins to plant vacuoles. PMID- 1739970 TI - The leucine-Lrp regulon in E. coli: a global response in search of a raison d'etre. PMID- 1739971 TI - Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. AB - A novel mechanism for inhibition of T cell responses is described. Using the recognition of the influenza hemagglutinin (HA) 307-319 peptide in the context of DR1 class II major histocompatibility complex molecules, we have found that nonstimulatory analogs of the HA peptide preferentially inhibit HA-specific T cells in inhibition of antigen presentation assays. This antigen-specific effect could be generalized to another DR1-restricted peptide, Tetanus toxoid 830-843. Direct binding and cellular experiments indicated that the mechanism responsible was distinct from competition for binding to DR1 molecules. Likewise, negative signaling and induction of T cell tolerance could also be excluded as effector mechanisms. Thus, the most likely mechanism for this effect is engagement of antigen-specific T cell receptors by DR1-peptide analog complexes, which results in antigen-specific competitive blocking of T cell responses by virtue of their capacity to compete with DR1-antigen complexes for binding to the T cell receptor. PMID- 1739972 TI - Introduction of intersubunit disulfide bonds in the membrane-distal region of the influenza hemagglutinin abolishes membrane fusion activity. AB - Influenza virus hemagglutinin (HA) mediates viral entry into cells by a low pH induced membrane fusion event in endosomes. A number of structural changes occur throughout the length of HA at the pH of fusion. To probe their significance and their necessity for fusion activity, we have prepared a site-directed mutant HA containing novel intersubunit disulfide bonds designed to cross-link covalently the membrane-distal domains of the trimer. These mutations inhibited the low pH induced conformational changes and prevented HA-mediated membrane fusion; conditions that reduced the novel disulfide bonds restored membrane fusion activity. We conclude that structural rearrangements in the membrane distal region of the HA are required for membrane fusion activity. PMID- 1739973 TI - A two-component regulatory system for self/non-self recognition in Ustilago maydis. AB - In U. maydis the multiallelic b locus controls sexual and pathogenic development. In the b locus a gene coding for a regulatory protein had been identified, and it was suggested that the interaction of two b polypeptides specified by different alleles programs sexual development in this fungus. We now demonstrate the existence of a second regulatory gene in the b locus. We term this gene bW and refer to the former as the bE gene. Both genes exist in many alleles. Although unrelated in primary sequence, both genes are similar in their overall organization. The gene products display allele-specific variability in their N terminal domains, show a high degree of sequence conservation in the C-terminal domains, and contain a homeodomain-related motif. Genetic evidence is provided to show that the pair of bE and bW polypeptides encoded by different b alleles is the key regulatory species. PMID- 1739974 TI - Caveolin, a protein component of caveolae membrane coats. AB - Caveolae have been implicated in the transcytosis of macromolecules across endothelial cells and in the receptor-mediated uptake of 5 methyltetrahydrofolate. Structural studies indicate that caveolae are decorated on their cytoplasmic surface by a unique array of filaments or strands that form striated coatings. To understand how these nonclathrin-coated pits function, we performed structural analysis of the striated coat and searched for the molecular component(s) of the coat material. The coat cannot be removed by washing with high salt; however, exposure of membranes to cholesterol-binding drugs caused invaginated caveolae to flatten and the striated coat to disassemble. Antibodies directed against a 22 kd substrate for v-src tyrosine kinase in virus-transformed chick embryo fibroblasts decorated the filaments, suggesting that this molecule is a component of the coat. We have named the molecule caveolin. Caveolae represent a third type of coated membrane specialization that is involved in molecular transport. PMID- 1739975 TI - Mechanism of specificity in the Fos-Jun oncoprotein heterodimer. AB - Fos and Jun, the protein products of the nuclear proto-oncogenes c-fos and c-jun, associate preferentially to form a heterodimer that binds to DNA and modulates transcription of a wide variety of genes in response to mitogenic stimuli. Both Fos and Jun contain a single leucine zipper region. Previous studies have shown that the leucine zippers of Fos and Jun are necessary and sufficient to mediate preferential heterodimer formation. The leucine zipper regions from Fos and Jun are also known to fold autonomously, most likely as two-stranded, parallel coiled coils. We show here that 8 amino acids from Fos and from Jun are sufficient to mediate preferential heterodimer formation in a background of the GCN4 leucine zipper sequence. Using pH titration and amino acid replacements, we also show that destabilization of the Fos homodimer by acidic residues provides a major thermodynamic driving force for preferential heterodimer formation. PMID- 1739976 TI - Ssn6-Tup1 is a general repressor of transcription in yeast. AB - The homeodomain protein alpha 2 and the SRF-like protein Mcm1 are required to establish cell type in the yeast Saccharomyces cerevisiae. Together, these regulatory proteins recognize a specific DNA operator, marking a set of genes for transcriptional repression. In this paper, we show that occupancy of the operator by alpha 2-Mcm1 is not sufficient to bring about repression. Rather, repression is effected only when Ssn6 (a TPR protein) and Tup1 (a beta-transducin repeat protein) are also present in the cell. We show that Ssn6 represses transcription when brought to a promoter by a bacterial DNA-binding domain and that Tup1 is required for this repression. Based on these and other results, we propose that Ssn6-Tup1 is a general repressor of transcription in yeast, recruited to target promoters by a variety of sequence-specific DNA-binding proteins. PMID- 1739977 TI - Yeast and human TFIID with altered DNA-binding specificity for TATA elements. AB - TFIID is the highly conserved, but species-specific, component of the RNA polymerase II transcription machinery that binds specifically to the TATA element (consensus TATAAA). Using a genetic selection, we isolated an altered specificity derivative of yeast TFIID that permits transcription from promoters containing a mutated TATA element (TGTAAA). Biochemical analysis indicates that this TFIID derivative has specifically gained the ability to bind TGTAAA efficiently. The mutant protein contains three substitutions within a 12 amino acid region; two of these are necessary and primarily responsible for the altered specificity. An analogous version of human TFIID, generated by introducing the same amino acid substitutions in the corresponding region of the protein, can support basal and GCN4-activated transcription in yeast cells from a TGTAAA-containing promoter. These results define a surface of TFIID that directly interacts with the TATA element, and they indicate that human TFIID can respond to acidic activator proteins in conjunction with the other components of the yeast transcription machinery. PMID- 1739978 TI - A far upstream estrogen response element of the ovalbumin gene contains several half-palindromic 5'-TGACC-3' motifs acting synergistically. AB - We have identified an estrogen-responsive enhancer element (DH3 ERE) in the estrogen-induced DNAase I-hypersensitive region III of the chicken ovalbumin gene, which is located approximately 3.3 kb upstream from the mRNA start site and does not contain palindromic ERE. Four TGACC half-palindromic motifs, separated from each other by more than 100 bp, are responsible for conferring estrogen inducibility either to the proximal ovalbumin gene promoter or to heterologous promoters. Thus, widely spaced half-palindromic ERE motifs can act synergistically. Each half-palindromic motif was shown to bind the estrogen receptor (ER) with a low efficiency in vitro. However, two widely spaced half palindromic motifs bound the ER cooperatively, much more efficiently than expected from binding to isolated half-ERE motifs. The ovalbumin promoter half palindromic ERE motif located close to the TATA box was required for the activity of the distal DH3 ERE, but could be replaced by the binding sites of other transactivators. PMID- 1739979 TI - U5 snRNA interacts with exon sequences at 5' and 3' splice sites. AB - U5 snRNA is an essential pre-mRNA splicing factor whose function remains enigmatic. Specific mutations in a conserved single-stranded loop sequence in yeast U5 snRNA can activate cleavage of G1----A mutant pre-mRNAs at aberrant 5' splice sites and facilitate processing of dead-end lariat intermediates to mRNA. Activation of aberrant 5' cleavage sites involves base pairing between U5 snRNA and nucleotides upstream of the cleavage site. Processing of dead-end lariat intermediates to mRNA correlates with base pairing between U5 and the first two bases in exon 2. The loop sequence in U5 snRNA may therefore by intimately involved in the transesterification reactions at 5' and 3' splice sites. This pattern of interactions is strikingly reminiscent of exon recognition events in group II self-splicing introns and is consistent with the notion that U5 snRNA may be related to a specific functional domain from a group II-like self-splicing ancestral intron. PMID- 1739980 TI - Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. AB - The promoter specificity of transcriptional activators is generally thought to be conferred by the specificity of the DNA-binding domain, which brings the activation domain to the appropriate promoter sequence. We show here, however, that Oct-1 and Oct-2 can differentially activate transcription not through DNA binding specificity but instead through the use of promoter-selective activation domains. These distinct activation domains lead to stimulation of the U2 small nuclear RNA promoter by Oct-1 and an mRNA promoter by Oct-2. An Oct-2 variant, called Oct-2B, differs from Oct-2 by an Oct-1-related C-terminal extension that results from alternative splicing. This variant gains the ability to activate the U2 small nuclear RNA promoter. Thus, the promoter selectivity of a transcriptional activator can be changed, in this case by alternative splicing, without affecting its DNA binding specificity. PMID- 1739981 TI - Articular chondrocytes secrete IL-1, express membrane IL-1, and have IL-1 inhibitory activity. AB - Previous work from our laboratory has shown that rabbit articular chondrocytes, like macrophages, produce reactive oxygen intermediates, express Ia antigen, and can mediate immunologic functions such as antigen presentation and induction of mixed and autologous lymphocyte reactions. We were interested in seeing if these cells could secrete interleukin-1 (IL-1) or express membrane form of IL-1 (mIL 1). Using the standard C3H/HeJ thymocyte assay, neither secreted IL-1 nor mIL-1 activity was detected in untreated or LPS-treated chondrocytes. However, the D10.G4.1 proliferation assay showed that chondrocytes, stimulated with LPS, secrete IL-1 and express the mIL-1 in a dose- and time-dependent manner. The IL-1 activity in LPS-stimulated chondrocyte supernatant and on fixed cells could be inhibited by anti-IL-1 antibodies. Sephadex G-75 chromatography of pooled, concentrated LPS culture supernatant resolved into two peaks of IL-1 activity at 13-17 and at 45-70 kDa, respectively. The bioactivity of chromatographic fractions were similar using both the thymocyte and D10.G4.1 bioassays. Western blot analysis of chondrocyte supernatant detects 17-kDa IL-1 beta; no processed 17-kDa IL-1 alpha was seen but IL-1 alpha-specific reactivity was observed at 64 kDa. Immunoblot analysis of chondrocyte lysates shows that cell-associated IL-1 is IL-1 alpha and is 37 kDa in size. PCR analysis shows the presence of mRNA for IL-1 beta and IL-1 alpha in LPS-treated cells; IL-1 beta mRNA was detected in untreated chondrocytes. The inability to detect IL-1 by the thymocyte assay is due to the presence of a chondrocyte inhibitor of IL-1 that can be demonstrated in cell sonicates, supernatants, and on paraformaldehyde-fixed chondrocytes. Chromatography of LPS-stimulated supernatant showed a peak of IL-1 inhibitory activity at 21-45 kDa. Chondrocytes which secrete IL-1 and express mIL-1 could play a critical role in maintaining chronic inflammation in rheumatoid arthritis. Therefore, the ability of chondrocytes to produce both IL-1 and an inhibitor to IL-1 is important in interpreting the mechanism of cartilage matrix maintenance and degradation. PMID- 1739982 TI - Control of experimental autoimmune uveoretinitis by low dose T cell vaccination. AB - Autoimmune T lymphocytes can be used under appropriate conditions to induce resistance to the specific autoimmune disease that they usually produce. This practice, termed T cell vaccination, was found to be effective with the injection of a low (subpathogenic) number of autoaggressive T line lymphocytes. We report here that T cell vaccination produced marked resistance to the expression of experimental autoimmune uveoretinitis (EAU) in Lewis rats. In addition, vaccination led to the appearance of lymphoid cells in the vaccinated rats that demonstrated proliferative responses against idiotypic and ergotypic specificities of the injected T cells. This is the first report demonstrating the effector T lymphocytes specific for ocular antigens may be used as agents to modulate immunopathogenic responses responsible for EAU. PMID- 1739983 TI - Corticosteroids inhibit the delivery of short-term activational pulses of phorbol ester and calcium ionophore to human peripheral T cells. AB - Although there is evidence that corticosteroids inhibit receptor-ligand-induced phospholipid hydrolysis, the immunosuppressive effects of these agents downstream of protein kinase C (PK-C) activation and cytosolic Ca2+ mobilization is unclear. Previous studies indicated that T cell proliferative activation could be achieved with simultaneous short-term (e.g., 15-120 min) exposure to agents activating PK C and elevating cytosolic Ca2+. In the studies reported here, similar procedures were utilized for determining whether corticosteroids alter T cell activation signals downstream of second messenger events. Dexamethasone interfered with T cell activation induced by short-term exposure to phorbol 12,13-dibutyrate (PDBu) and the calcium ionophore, ionomycin. The inhibitory effect was evident with as little as 15 min of exposure to dexamethasone and T cell activating agents, making mechanisms involving de novo protein synthesis unlikely. Dexamethasone's effects in this system were blocked by the steroid receptor antagonist RU-486, indicating that the inhibition was mediated through the glucocorticoid receptor. The inclusion of recombinant interleukin-2 (IL-2) only partially overcame the dexamethasone inhibitory effect. Long-term (i.e., 48 hr) direct stimulation of PK C with either PDBu or the non-tumor-promoting PK-C activator, bryostatin 1, also substantially overcame dexamethasone's effects, resulting in a recovery of IL-2 production and significant restoration of the T-cell proliferative response. These observations suggest that treatment with a PK-C-activating agent such as bryostatin 1 could reduce glucocorticosteroid-induced immunosuppression. PMID- 1739984 TI - Differential regulation of IgA production by TGF-beta and IL-5: TGF-beta induces surface IgA-positive cells bearing IL-5 receptor, whereas IL-5 promotes their survival and maturation into IgA-secreting cells. AB - Transforming growth factor beta (TGF-beta) and IL-5 have been shown to augment IgA production by LPS-stimulated murine B cells. We investigated the effect of TGF-beta on the expression of surface Ig-isotype and IL-5 receptor on LPS stimulated B cells. TGF-beta increased the proportion of both surface IgA positive (sIgA+) B cells and sIgG2b+ B cells and enhanced IgA and IgG2b production by LPS-stimulated B cells. TGF-beta synergized with IL-5 only for IgA production of the seven Ig-isotypes and in combination with IL-5 caused a significant increase in the proportion of sIgA+ B cells up to 17.4%. In contrast, IL-5 decreased the proportion of sIgG2b+ B cells and sIgG3+ B cells and inhibited the production of IgG2b and IgG3 by LPS-stimulated B cells. About 50% of sIgA+ cells induced by TGF-beta expressed IL-5 receptor. They secreted peak levels of IgA and seemed to maintain long viability in the presence of IL-5; whereas TGF beta had the opposite effects on sIgA+ B cells and down-regulated the IL-5 receptor expression. These results indicate that TGF-beta increases the number of sIgA(+)- and IL-5 receptor-positive B cells which respond to IL-5 giving rise to IgA-secreting cells and also support the notions that TGF-beta preferentially induces switching to sIgA+ B cells and IL-5 induces the maturation of postswitch sIgA+ B cells into IgA-secreting cells in a stepwise fashion. PMID- 1739985 TI - Induction of macrophage interleukin-1 production by Listeria monocytogenes hemolysin. AB - Listeriolysin O produced by a hemolytic strain of Listeria monocytogenes was purified from the ammonium sulfate precipitate of a culture supernatant through the steps of ion-exchange chromatography and gel filtration. The purified hemolysin finally gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 58,000. When peritoneal exudate macrophages were stimulated with purified hemolysin, we found a high level of IL 1 activity as determined by thymocyte costimulator assay in the culture supernatant. Cell-associated and intracellular IL-1 activity was also detected. The activity in the supernatant or membrane was blocked by polyclonal antibody to murine IL-1 alpha. Moreover, IL-1-specific mRNA expression could be detected in the macrophages stimulated with listeriolysin O by Northern blot analysis. Possible contamination by LPS of the listeriolysin O preparation did not seem to contribute to the induction of macrophage IL-1 production. PMID- 1739986 TI - Mechanisms involved in NK resistance induced by interferon-gamma. AB - Human tumor cell lines were treated with interferon-gamma (IFN-gamma) and then used as target cells in NK assays to measure their ability to form conjugates and stimulate the production of NK cytotoxic factors (NKCF) and to determine their susceptibility to NKCF lysis. K562 and cell lines RS1, RS3, RS7, CAC, and CAP2, obtained from solid brain tumors, were used as targets, and peripheral blood lymphocytes (PBL) from normal donors were used as effector cells. IFN-gamma treated cell lines had a decreased susceptibility to NKCF lysis and a decreased ability to induce the release of these factors without affecting target-effector cell binding. These results were not due to changes in HLA class I antigen expression, given that the level of HLA class I antigens on the tumor cell lines was not affected, the only exception being K562. In an attempt to further clarify the possible influence of HLA class I expression on K562, IFN-gamma-pretreated K562 cells were separated into HLA class I positive and HLA class I negative subsets for the NK assays. The results showed that both populations behaved similarly upon target-effector conjugate formation, whereas the HLA class I positive population showed a reduced susceptibility to lysis by NK cells and NKCF. Thus, these results establish that NK resistance induced by IFN-gamma is mediated by blocking the target cell's ability to activate NK cell triggering and release of NKCF and by blocking its susceptibility to lysis by these factors. This analysis helps to clarify not only the NK process but also the controversial regulatory effect of IFN in NK lysis. PMID- 1739987 TI - Antigen recognition and IL-2 receptor gene expression as evidence against clonal deletion in mice with neonatally induced transplantation tolerance. AB - Neonatal transplantation tolerance was induced in B10.A mice by the injection of spleen and bone marrow cells from semiallogeneic [C57BL/10(B10) x B10.A] F1 donors. The neonatally treated mice accepted skin grafts from B10 donors. Spleen cells from tolerant animals did not respond by proliferation to tolerated B10 antigens in vitro. However, spleen cells from tolerant mice recognized specific (B10) antigens and synthesized mRNA for the inducible 55-kDa interleukin-2 receptor (IL-2R) as did cells from normal animals. Maintenance of this early phase of cell activation upon contact with tolerated antigens is direct evidence against clonal deletion as a mechanism, in this particular model of neonatally induced transplantation tolerance. PMID- 1739988 TI - Protective immunity and granulomatous inflammation is mediated in vivo by T cells reactive to epitopes common to avirulent and listeriolysin-negative mutants of Listeria monocytogenes. AB - The ability of several listeriolysin O-negative mutants of the EGD and NCTC 7973 strains of Listeria monocytogenes to activate specific T cell responses in vitro and in vivo was determined. T cell lines from different inbred mouse strains and derived T cell clones elicited by L. monocytogenes, strain EGD, which are able to adoptively transfer protection and granuloma formation were examined. Specificity testing revealed no differences between listeriolysin-positive and -negative strains to induce proliferation of the T cell lines and clones. Similar results were obtained when we examined CD4+ T cell-mediated granuloma formation in the livers of mice previously immunized with viable bacteria of the virulent strain. Granulomatous inflammation could be elicited by iv application of heat-killed bacteria of listeriolysin-positive and of -negative bacteria. Protective immunity to listerial infections and granulomatous inflammation therefore appears to be mediated by T cells recognizing epitopes on listerial antigens that are shared by both pathogenic and nonpathogenic Listeria strains. PMID- 1739989 TI - Inhibition of the anti-CD3-induced T cell proliferation by crosslinking of stimulatory antibodies in the presence of PMA and interleukin-2. AB - Anti-CD3 antibodies are directed to the nonpolymorphic part of the T cell receptor complex and may activate human peripheral T cells. Under some circumstances crosslinked anti-CD3 has been described to augment the proliferative response. Here we demonstrate that crosslinking of stimulatory anti CD3 antibodies by anti-IgG in cell suspension abolishes their effect on proliferation of human resting peripheral T cells in the presence of PMA and/or IL-2. This effect was observed within a wide range of anti-CD3 concentrations (1 ng/ml to 1 microgram/ml) independent of the presence of monocytes. The inhibition was not due to the induction of cell death, since cells remained propidium iodide negative after treatment. Protein-tyrosine phosphorylation after anti-CD3 crosslinking was more pronounced than in the presence of noncrosslinked anti-CD3. This indicates that the signal was transmitted after anti-CD3 crosslinking, however, it was unable to induce T cell proliferation. Reduced IL-2 receptor expression after anti-CD3 crosslinking and the inability of exogenous IL-2 to restore the proliferative response might indicate a reduced susceptibility to IL 2 as a reason for the described phenomenon. PMID- 1739990 TI - [Color vision in pseudophakia]. AB - The authors compare colour differentiation of 30 phakic and 30 pseudophakic eyes, using the Farnsworth-Munsell 100-hue test. No significant difference was found between the two groups as regards differentiation of colours although theoretically it could be expected that colour differentiation will be better in eyes with a synthetic intraocular lens. The factor which has the greatest influence on colour sense is the subject's age. PMID- 1739991 TI - [Changes in color differentiation using the 100-Hue Test. I. The total score on the test in relation to age]. AB - The authors investigated colour differentiation, using the FM 100-hue test in healthy subjects without hypertension and diabetes and with a normal ophthalmological finding and normal functions. They examined 120 subjects, i.e. 240 eyes--120 male eyes and 120 female eyes in six decades from 21-80 years. The examination revealed a significant diminution of colour differentiation with advancing age but no difference in colour differentiation between men and women. The tests can be considered at the same time a basic orientation standard for evaluation of colour differentiation. PMID- 1739992 TI - [Hamartomas of the optic disc and adjacent retina]. AB - The authors discuss some formations on the optic disk and close neighbourhood resembling tumours. They originate from various cellular elements in that area and are described as hamartomas. A progressive growth was recorded only in vascular hamartomas after unsuccessful therapeutic intervention, the remainder were stationary during observation periods of various lengths. PMID- 1739993 TI - [Changes in color differentiation using the 100-Hue Test. II. The score for basic colors of the spectrum in relation to age]. AB - The author investigated changes of colour sensitivity of red, green and blue, using the FM 100-hue test. For examination healthy subjects without hypertension and diabetes and with a normal ophthalmological finding and normal functions were selected. In six age groups (21-80 years) 240 male and female eyes were examined. In the youngest age group there was greatest proportion of errors in the blue area, less in the green area and the least in the red area. A more detailed analysis revealed that the greatest rate of errors was in the blue-green area. With advancing age the number of errors in the areas of the basic colours increase and at the same time differences between differentiation of red, green and blue decrease. In the age group above 71 years no differences were found in the score of errors in the area of basic colour. PMID- 1739994 TI - [Clinical index for prediction of visual acuity after cataract surgery--personal experience]. AB - The authors are giving an account of their own experience with the clinical index for prediction of the visual acuity after cataract surgery. The index uses the following data - age, visual acuity before operation, number of regularly taken drugs and frequency of reading before operation. In 171 eyes of patients operated on account of cataract by different techniques (the patients were not specially selected and some suffered from other eye diseases), the authors found a close agreement between the vision predicted by means of the clinical index and the final visual acuity after operation. Agreement was recorded in 68%. The authors recommend the clinical index for more extensive clinical tests. PMID- 1739995 TI - [Calculations for intraocular lenses]. AB - The authors deal with the postoperative dioptric deviation from the calculated optic potency of the emetropic intraocular lens, using formulae SRK II, SRK/T and Holladay's formula. Within the range +/- 1.5 D the deviation varied in 84% of the operated eyes where the intraocular lens was assessed according to formula SRK II; in 76% when formula SRK/T was used and in 74% when Holladay's formula was used. The authors give also an account of possible sources of errors during measurement, calculation and evaluation of results. PMID- 1739996 TI - [Objective evaluation of the success of treatment in exudative diabetic maculopathy]. AB - The effectiveness of pharmacological and laser treatment of diabetic maculopathy was evaluated so far according to the change of visual acuity and the ophthalmoscopic picture. Computer comparison of the size of the photographic picture of the circinata before treatment and in the course of treatment makes objective evaluation of treatment of exudative diabetic maculopathy possible. PMID- 1739997 TI - [Thrombolysis of arterial retinal occlusion using urokinase]. AB - The authors present an account on possible aimed thrombolytic treatment of occlusion of the retinal artery by urokinase. Aimed thrombolysis can be performed at ophthalmological departments with an available radiodiagnostic department, which performs angiographies of carotid arteries. The authors discuss the necessary dose of 200,000 to 300,000 i.u. of urokinase. One-hour infusion with an initial booster dose is best. Early administration of the preparation is considered most important by the authors. The authors present the case-history of a 34-year-old patient with complete occlusion of the central retinal artery with haemodynamically severe aortal stenosis with a congenital background. Urokinase was administered six hours after occlusion of the artery. Gradually reperfusion of the retina occurred and improvement of the visual acuity from 0.01 to 0.17 with a residual relative wedge-shaped loss of the visual field and paleness of the disc of the optic nerve. PMID- 1739998 TI - [Ocular changes in Alport's syndrome]. AB - In a group of 17 patients with Alport's syndrome changes on the ocular fundus were detected in 35.3% without influence on the central visual acuity. At the same time a statistically significant reduction of sensitivity to contrast was proved. ERG examination revealed statistically significant changes in the a and b wave as regards steepness and in the b wave also as regards amplitude. PMID- 1739999 TI - [Changes in the visual field after laser coagulation in type I diabetics]. AB - The authors examined 41 eyes of 22 compensated type I diabetics 1 - 2 years after laser photocoagulation, using an automatic static perimeter Peritest. One fifth of the investigated patients had marked changes - DR20. The patients are not aware of the diminution of the visual field. Even the most extensive diminution of the visual field in this group did not restrict the ability to drive motor vehicles. PMID- 1740000 TI - [Treatment of chronic uveitis with long-term administration of penicillin]. AB - The authors followed up a group of 20 patients with chronic uveitis (10 men and 10 women), mean age 36.5 years. Despite treatment of the foci, they suffered on average from seven relapses of the disease, frequently several times in the course of one year. From the anamnestic aspect there was a significantly high number of spells of tonsillitis, respiratory infections and arthralgia. Half the cases of uveitis, mainly anterior, were bilateral. The patients suffered from dysimmunoglobulinaemia with low values of FW, ASLO, Latex. HLA B 27 was positive in five subjects. After one-year of Pendepon or Penclen administration (in half the patients with NORG) 18 patients did not develop a relapse for a period of 2-3 years. The method is simple, cheap, easy to use in field practice, in particular in junior patients. The clinical effect of treatment justifies the use of this method as an alternative of intermittent immunosuppression. PMID- 1740001 TI - [Keratoplasty in children]. AB - The authors report anatomical and functional results of 24 keratoplasties in children aged 7 months to 15 years, incl. analysis of peroperative and postoperative complications. A total of 24 keratoplastics were performed on 20 eyes of 20 children. The mean follow up period was 2.1 years. Nineteen times the first operation was involved, three times the first, twice the second rekeratoplasty. The most frequent postoperative complication was an immunological reaction of the disk which occurred in 33%. It caused turbidity of five disks. After keratoplasty 11 disks remained transparent (45.8%), 10 disks became turbid (41.7%) and three disks semitransparent (12.5%). A visual acuity of 6/12 or better was recorded in 7 eyes (39%) and 6/60 and better in 6 eyes (30%). The cause of reduced visual acuity beneath 6/12 with a clear disk was in three instances amblyopia, in one case nystagmus. PMID- 1740002 TI - [Diseases of the pupil]. PMID- 1740003 TI - Transgeneration transmission of carcinogenic risk. PMID- 1740004 TI - 2-Aminofluorene-DNA adducts in mouse urinary bladder: effect of age, sex and acetylator phenotype. AB - Formation of urinary bladder DNA-2-aminofluorene adducts in inbred and acetylator congenic mice was measured 3 h after a 60 mg/kg dose of the arylamine carcinogen. The sensitivity of 32P-postlabeling with HPLC analysis permitted quantitation of adducts in individual mouse bladders. Acetylator phenotype was a significant determinant of DNA damage in female mice as slow acetylators had higher levels of bladder DNA adducts than rapids. This correlation is the reverse of that seen with hepatic DNA. Age was also a significant determinant of DNA damage as older mice (20-23 weeks) formed more bladder DNA adducts than young (7 week) mice. The age-related increase in bladder adduct formation was seen in both sexes of all mouse lines. Male B6 mice exposed to 2-aminofluorene at 20-23 weeks of age showed a 26-fold higher level of bladder DNA adducts than males exposed at 7 weeks. In addition to the large increase in total adduct level, the older male B6 mice produced significant amounts of an unidentified, early-eluting adduct peak that had chromatographic properties similar to an aminofluorene-DNA adduct produced through peroxidative activation. These results indicate that age, sex and acetylator phenotype are all important determinants of aromatic amine-bladder DNA adduct formation in mice. PMID- 1740005 TI - Cytochrome P450IA expression in adult and fetal human liver. AB - A monoclonal antibody has been produced that recognizes the cytochrome P450 form, cytochrome P450IA1, but not cytochrome P450IA2 in rats and recognizes a single protein band of similar mol. wt on immunoblots of human liver microsomes. Immunohistochemical studies have been carried out with this antibody to investigate the localization and distribution of cytochrome(s) P450 of the P450IA family in human liver. Cytochrome P450IA was identified in both adult and fetal liver and in each case it was localized predominantly to hepatocytes. In adult liver there was a heterogeneous distribution of cytochrome P450IA immunoreactivity with cytochrome P450IA mainly present in zone 3 hepatocytes of the liver acinus. Within fetal liver there was a uniform distribution of cytochrome P450IA immunoreactivity with no apparent zonal distribution. Bile duct epithelium did not show definite immunostaining for cytochrome P450IA in either adult or fetal liver. PMID- 1740006 TI - Enhanced induction of epidermal ornithine decarboxylase activity in C57BL/6 compared to DBA/2 mice by protein kinase C-activating skin tumor promoters: relevance to genetically mediated differences in promotion susceptibility. AB - Previous work from our laboratory demonstrated that 12-O-tetradecanoylphorbol-13 acetate (TPA) or a synthetic diacylglycerol induced significantly higher epidermal ornithine decarboxylase (ODC) activity in C57BL/6 than in DBA/2 mice. To understand further the genetic basis for this strain difference, two tumor promoters were evaluated for their effects on epidermal ODC activity: teleocidin, which activates protein kinase C (PKC); and 1,8-dihydroxyl-3-methyl-9-anthrone (chrysarobin), which does not. In addition, the ODC induction response in B6D2F1 offspring and BXD recombinant inbred (RI) strains was examined following multiple treatments with TPA. A single topical application of teleocidin to mouse dorsal skin led to the hyperinduction of epidermal ODC activity in C57BL/6 mice. In contrast, while chrysarobin induced epidermal ODC activity, no significant differences in the magnitude of this response were observed in SENCAR, DBA/2 or C57BL/6 mice. Consistent with our previous findings, the magnitude of ODC induction by teleocidin in these three mouse lines (C57BL/6 greater than SENCAR greater than DBA/2) did not correlate with their susceptibility to tumor promotion by TPA (SENCAR greater than DBA/2 greater than C57BL/6). ODC activity induced by multiple application of TPA in B6DF1 mice, whose susceptibility to phorbol ester tumor promotion is inherited as an incomplete dominant trait, was comparable to that induced in C57BL/6 mice at all the doses examined. Cluster analysis of TPA-induced ODC activity in BXD RI strains allowed us tentatively to group them into four or five phenotypes and to estimate a minimum of two genetic loci controlling TPA-induced ODC activity. Furthermore, in BXD RI strains, there was no apparent relationship between the magnitude of ODC induction and responsiveness to tumor promotion or sustained hyperplasia. Collectively, these results suggest that hyperinducibility of ODC in response to PKC-activating tumor promoters is inherited as an autosomal dominant trait, and that genetic determinants for ODC induction, at least in C57BL/6 and DBA/2 mice, appear completely independent of those controlling tumor promotion susceptibility. PMID- 1740007 TI - UVC modulation of epidermal growth factor receptor number in HeLa S3 cells. AB - Induction of transforming growth factor alpha (TGF alpha) in human cell lines by 254 nm ultraviolet radiation (UVC) suggests that TGF alpha may have an autocrine role in UV-induced tumorigenesis. Binding of TGF alpha to epidermal growth factor receptor (EGFR) is an important initial step in transducing the signal for cell division. Experiments reported herein were designed to determine whether, in addition to inducing TGF alpha, UVC might also induce changes in the levels of EGFR on HeLa S3 cells [125I]EGF binding to HeLa S3 cells was inhibited 8 h after exposure to 7 J/m2 UVC radiation followed by increased [125I]EGF binding 16-32 h after irradiation. Scatchard analysis of EGF binding at 28 h indicated that irradiated cells had 60% more receptors with no differences in apparent binding affinities (56,300 +/- 5494 receptors versus 34,900 +/- 1899 receptors in sham irradiated cells). Cell cycle analysis at 8 h post-UVC indicated that cells had slowed traverse of S-phase, but by 24 and 48 h, times at which increases in [125I]EGF were evident, cell cycle distributions were essentially back to normal. These results indicate that UVC modulates EGFR numbers in HeLa S3 cells and suggest that solar radiation may modulate EGFR numbers in keratinocytes or other cells in the skin. The presence of UV-induced growth factors such as TGF alpha and increased levels of EGFR may result in sustained cell proliferation by autocrine or paracrine mechanisms. These populations of cycling cells would then be at risk for subsequent mutational events that result in transformation to a tumorigenic state. PMID- 1740008 TI - JB6 murine epidermal cell lines sensitive and resistant to 12-O tetradecanoylphorbol-13-acetate (TPA)-induced transformation exhibit differential arachidonic acid metabolism in response to TPA and the calcium ionophore A23187. AB - In a study of arachidonic acid metabolism in murine epidermal JB6 cells, promoter sensitive (P+) and promoter-resistant (P-) variants, labeled with [3H]arachidonic acid, were treated successively with 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. Released radiolabel was separated by HPLC and identified by coelution of standards. Prostacyclin release was then quantified by radioimmunoassay for 6-keto prostaglandin (PG)F1 alpha. A23187 alone resulted in a small but significant enhanced release of radiolabel from both cell variants (0.7 +/- 0.2% for P- and 0.6 +/- 0.3% for P+ cells; mean +/- SD). Treatment with TPA and subsequent treatment with A23187 resulted in a synergistically enhanced release of radiolabel from both cell variants (4.1 +/- 0.8% for P- and 3.4 +/- 0.9% for P+ cells) relative to that with either agent alone. Although the predominant product for each treatment regimen was prostaglandin E2 (PGE2), the TPA-resistant cells (P-) released significantly more 6-keto PGF1 alpha, a stable breakdown product of PGI2, than did the TPA-sensitive (P+) cells. These results indicate differential arachidonic acid metabolism between JB6 cell variants resistant and sensitive to TPA-induced transformation. PMID- 1740009 TI - Investigation of the covalent binding of styrene-7,8-oxide to DNA in rat and mouse. AB - Styrene-7,8-oxide (SO), the main intermediate metabolite of styrene, induces hyperkeratosis and tumors in the forestomach of rats and mice upon chronic administration by gavage. The aim of this study was to investigate whether DNA binding could be responsible for the carcinogenic effect observed. [7-3H]SO was administered by oral gavage in corn oil to male CD rats at two dose levels (1.65 or 240 mg/kg). After 4 or 24 h, forestomach, glandular stomach and liver were excised, DNA was isolated and its radioactivity determined. At the 4 h time point, the DNA radioactivity was below the limit of detection in the forestomach and the liver. Expressed in the units of the covalent binding index, CBI = (mumol adduct/mol DNA nucleotide)/(mmol chemical administered/kg body wt), the DNA binding potency was below 2.6 and 2.0 respectively. In the glandular stomach at 4 h, and in most 24 h samples, DNA was slightly radiolabeled. Enzymatic degradation of the DNA and separation by HPLC of the normal nucleotides showed that the DNA radioactivity represented biosynthetic incorporation of radiolabel into newly synthesized DNA. The limit of detection of DNA adducts in the glandular stomach was 1.0. In a second experiment, [7-3H]SO was administered by i.p. injection to male B6C3F1 mice. Liver DNA was analyzed after 2 h. No radioactivity was detectable at a limit of detection of CBI less than 0.6. In agreement with the relatively long half-life of SO in animals, the chemical reactivity of SO appears to be too low to result in a detectable production of DNA adducts in an in vivo situation. Upon comparison with the DNA-binding of other carcinogens, a purely genotoxic mechanism of tumorigenic action of SO is unlikely. The observed tumorigenic potency in the forestomach could be the result of strong tumor promotion by high-dose cytotoxicity followed by regenerative hyperplasia. PMID- 1740010 TI - Contributions of human liver cytochrome P450 enzymes to the N-oxidation of 4,4' methylene-bis(2-chloroaniline). AB - 4,4'-Methylene-bis(2-chloroaniline) (MOCA) can produce tumors in rodents and dogs and an increased incidence of bladder tumors has been reported in exposed workers. It is therefore of interest to identify the human cytochrome P450 (P450) enzymes involved in MOCA N-oxidation, the primary reaction involved in the formation of an electrophilic product. Human liver microsomes were fractionated and MOCA N-oxidation activity was monitored through the procedure. The most active enzyme fraction corresponded to P450 3A4, as determined by immunochemical assays and N-terminal amino acid sequence analysis. Yeast recombinant P450 3A4 also had MOCA N-oxidation activity. Purified human liver P450 2A6 showed catalytic activity; however, anti-P450 2A6 inhibited less than 20% of the microsomal activity while anti-P450 3A4 inhibited up to 75%. Levels of marker activities of both P450 3A4 (nifedipine oxidation) and P450 2A6 (coumarin 7 hydroxylation) were measured in a set of human liver microsomes and both were correlated with MOCA N-oxidation rates. Gestodene and troleandomycin inhibited up to half of the microsomal MOCA N-hydroxylation activity but 7,8-benzoflavone showed only slight inhibition. Anti-P450 3A4 inhibited (up to 80% of) the microsomal transformation of MOCA to a product genotoxic as judged by bacterial SOS response. The work indicates that P450 3A4 makes a major contribution to human liver microsomal MOCA N-oxidation, and P450 2A6 has a minor role. P450 1A2, which catalyzes the hydroxylation of many arylamines, does not contribute to a great extent. PMID- 1740011 TI - Mutagenicity in V79 cells of N-nitrosobis(2-hydroxypropyl)amine and N nitrosobis(2-oxopropyl)amine activated by tissues from hamsters fed low and high fat diets. AB - Hepatocytes and pancreas duct tissues from male Syrian hamsters fed high-fat (HFD) and low-fat (LFD) diets were used to activate N-nitrosobis(2 hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP) in the V79 cell mutagenicity assay. V79 DNA alkylation by BHP and BOP was also measured. There was a 3.5-fold increase in BHP mutagenicity but only a 1.4-fold increase in BOP mutagenicity when hepatocytes from HFD-fed hamsters were used over the mutagenicity when hepatocytes from LFD-fed hamsters were used. When pancreas duct tissue was the activating system there was a 2-fold increase in BHP and BOP mutagenicity. O6-Methylguanine levels in V79 DNA rose 4-fold when hepatocytes from HFD-fed hamsters were used to activate BOP but they declined when BHP was the alkylating agent. PMID- 1740012 TI - Endogenous glutathione levels modulate both constitutive and UVA radiation/hydrogen peroxide inducible expression of the human heme oxygenase gene. AB - Induction of the expression of the mammalian heme oxygenase gene appears to be a general response to oxidant stress. In view of the role of glutathione in protecting cells against solar UVA radiation and other forms of oxidant stress, we have investigated the relationship between intracellular glutathione levels and the inducibility of the human heme oxygenase gene after treatment of populations of cultured skin fibroblasts with either UVA radiation or hydrogen peroxide. We observe a clear relationship between cellular glutathione status and both the constitutive and oxidant-inducible accumulation of heme oxygenase mRNA. Glutathione depletion may lead to enhanced gene expression either as a result of the potentiated accumulation of active oxygen intermediates or as a result of the direct influence of glutathione on a critical target involved in signal transduction. PMID- 1740013 TI - Investigation on the carcinogenic effects of coal tar pitch in rat respiratory tract by intratracheal instillations. AB - The effects of coal tar pitch (CTP) on the tracheobronchial mucosa of Wistar rats were studied. Three groups of animals received 10 weekly intratracheal instillations of CTP at the cumulative doses of 6.48, 136.56 and 200 mg respectively. The control group of rats received 10 weekly intratracheal instillations of charcoal powder at a cumulative dose of 20 mg. The study in which the animals were killed serially revealed that CTP had conspicuous damage on the respiratory system of rats, especially on the bronchiolo-alveolar areas. The lesions induced by CTP ranged from hyperplastic, metaplastic and dysplastic changes to extensive cancers. These lesions were usually multifocal, and were more severe in the rats receiving higher dosages of CTP. The deposition of CTP particles within or adjacent to these lesions could be readily identified. Lung cancers occurred in 12.5% (4/32) and 25% (10/40) of the rats treated with 136.56 and 200 mg of CTP, whereas no tumors were found in control rats and the rats that received 6.48 mg of CTP. The overall cancer incidence significantly related to the cumulative dose of CTP. The histological types of lung cancers consisted of squamous cell carcinomas (10 out of the 14 lung cancers), adenocarcinoma (1/14), and combined squamous and adenocarcinomas (3/14). The development of CTP-induced rat lung cancers appears to derive from the hyperplasias of bronchiolo-alveolar epithelium, and processing stages of squamous metaplasias and/or dysplasias to carcinomas. The present results confirmed the carcinogenic effects of CTP on the respiratory system of rats, and provided experimental evidence for human lung carcinogenesis, particularly in those occupationally exposed to coal tars or tar products. PMID- 1740014 TI - Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats. AB - Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O (2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides. PMID- 1740015 TI - Induction of 8-hydroxydeoxyguanosine in Ah-responsive mouse liver by iron and Aroclor 1254. AB - Treatment of Ah-responsive C57BL/10ScSn mice with iron greatly sensitizes them to induction of hepatic porphyria and tumour formation by the polychlorinated biphenyl mixture Aroclor 1254. In the present studies, male C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% Aroclor 1254 for 1, 3 and 5 weeks. By use of HPLC with electrochemical detection, 8-hydroxydeoxyguanosine (8-OHdG) was then measured in liver DNA as a marker for oxidative damage. Treatments with iron or Aroclor alone did not result in a significant increase in 8-OHdG except at 3 weeks following iron treatment. At 1 and 3 weeks 8-OHdG levels were induced approximately 3- and 5-fold above control groups respectively in iron- and Aroclor-treated animals. Although there was an apparent 5- to 10-fold increase in the level of 8-OHdG at 5 weeks, this was partially attributed to the in vitro effects of porphyrins, levels of which were massively elevated in liver at this time point. The iron/Aroclor-induced synergistic elevation of 8-OHdG at 1 and 3 weeks was concluded to be due to in vivo damage, thus suggesting the importance of DNA oxidation in the early events of carcinogenesis in this system. PMID- 1740016 TI - Differential sensitivities of transplacentally initiated newborn mouse epidermal cells to different tumor promoters. AB - Epidermal cells isolated from newborn mice and cultured in low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as monolayer. An increase in the medium Ca2+ concentration to normal level (1.8 mM) induced terminal differentiation of epidermal cells. Epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) produced a small number of rapidly growing cellular foci with epidermal morphology when the medium Ca2+ concentration was raised to normal level. The number of these Ca(2+)-induced differentiation-resistant colonies increased with increasing doses of DMBA, indicating that the differentiation-resistant colonies are the cells initiated by DMBA. Three differentiation-resistant colonies were cloned and designated as WY-1, WY-18 and WY-20 cells. All of these cell lines grew rapidly in the normal Ca2+ medium but not in the low Ca2+ medium. A potent skin tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and other TPA type second-stage tumor promoters such as mezerein and 12-O-retinoylphorbol-13 acetate, stimulated the growth of WY-18 and WY-20 cells in the low Ca2+ medium, but did not stimulate the growth of WY-1 cells. TPA stimulated DNA synthesis and ornithine decarboxylase induction in WY-18 and WY-20 cells but not in WY-1 cells. A non-TPA-type tumor promoter, okadaic acid, failed to stimulate the growth of these three cell lines. Another non-TPA-type tumor-promoting agent, 7-bromo methylbenz[a]anthracene, also failed to stimulate the growth of WY-1 and WY-20 cells but stimulated the growth of WY-18 cells. WY-18 and WY-20 cells formed colonies in soft agar but WY-1 cells did not form colonies. When these cell lines were injected s.c. into nude mice, WY-1 cells produced fast-growing tumors, whereas WY-18 and WY-20 cells produced relatively slow-growing tumors. Our present results indicate that each initiated cell has different sensitivities for different types of tumor promoters, and each type of promoter acts on corresponding types of initiated cells. PMID- 1740017 TI - Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. AB - We initiated this study to determine whether three structurally related bifunctional alkylating agents could induce the expression of a presumptive human DNA repair gene. The gene chosen for this study is known to encode the ribosomal phosphoprotein PO, but ironically may also share functions related to DNA repair. We now show by Northern analysis that PO is induced by L-phenylalanine mustard, 4 hydroperoxycyclophosphamide and mechlorethamine, which are DNA-damaging agents commonly used as chemotherapeutic antitumor agents. In further support of its involvement in DNA repair is the finding of a 30- to 50-fold constitutive overexpression of the PO gene in human tumor cell lines that are Mer-, cells which lack O6-methylguanine methyltransferase activity, when compared to Mer+ cell lines. This constitutively elevated level of PO in Mer- cell lines, which are thus DNA repair defective for O6-alkyguanine lesions, was not observed for other genes tested, including the human ribosomal gene S17 whose mRNA steady state levels were uniformly the same in both Mer- and Mer+ cells. Taking these data together, it appears that increased levels of PO are somehow linked to DNA repair, and increased expression of PO may compensate for the decreased O6 methylguanine DNA methyltransferase activity in Mer- cells. Furthermore, the PO gene has also been shown to be overexpressed in colorectal tumors and polyps and the sera of some systemic lupus erythematosus patients contain antibodies against PO. The titer of the anti-PO antibodies rises significantly during lupus psychosis. PMID- 1740018 TI - Loss of peroxisomal enzyme expression in preneoplastic and neoplastic lesions induced by peroxisome proliferators in rat livers. AB - Immunohistochemical staining of enoyl CoA hydratase (ECH), a key peroxisomal enzyme, revealed that the putative preneoplastic lesions induced in livers by administration of the peroxisome proliferator (PP) clofibrate (0.3% in diet) to rats for 60 weeks or more, lacked this enzyme so that they could be detected as ECH-negative foci. ECH and other peroxisomal enzymes such as acyl CoA oxidase, catalase and carnitine-dependent acetyltransferase were also either not or only weakly expressed in most hepatic hyperplastic nodules and hepatomas induced by ciprofibrate (0.025% in diet), Wy-14,643 (0.1%) or BR-931 (0.2%), while being strongly induced in surrounding hepatocytes. These results indicate that the expression of ECH and other peroxisomal enzymes is repressed in putative preneoplastic and neoplastic lesions induced by PPs in rat livers and that these peroxisomal enzymes might therefore be used as negative markers. PMID- 1740019 TI - Rat pituitary changes observed with magnetic resonance imaging following removal of estrogen stimulus: correlation with histopathology and immunohistology. AB - The effect of estrogen withdrawal on pituitary glands of rats treated with estradiol-17 beta for various lengths of time was monitored by magnetic resonance imaging (MRI) and histological examination. Estrogen pellets were removed at seven different time points ranging from 4 to 206 days after pellet implantation. High-resolution mid-sagittal MR images of the rat head were made 1 day before pellet implantation, immediately following pellet withdrawal, and 14 and 28 days after pellet withdrawal. Twenty-eight days after pellet withdrawal pituitary glands were fixed and processed for histological examination. Enlarged pituitaries were detected by MRI from 16 days after implantation and onwards. Twenty-eight days after estrogen withdrawal the typical triangular shape of the normal pituitary had returned and pituitary morphology was indistinguishable from that of normal pituitaries in all rats that had been treated with estrogen for up to 114 days. Pituitaries of rats that had received estrogen for 186 days had a normal MR image 28 days after estrogen withdrawal, but microscopic examination revealed multifocal hyperplasias of prolactin-positive cells throughout the pars distalis. MRI of rats treated for 206 days showed tumorously enlarged pituitaries. There was no evidence of tumor regression in these rats 28 days after pellet removal. It was concluded that hypertrophic pituitaries regained a normal size, shape and morphology after estrogen withdrawal, except for a remarkable type of hyperplasia following estrogen treatment for 186 days and a recovery period of 28 days. In tumorous pituitaries no regression of lesions was noticed. PMID- 1740020 TI - Enhancement by nickel(II) and L-histidine of 2'-deoxyguanosine oxidation with hydrogen peroxide. AB - Conversion of the 2'-deoxyguanosine (dG) residues in calf thymus DNA to 8-hydroxy 2'-deoxyguanosine (8-OH-dG) was achieved at physiological pH by treating the DNA with hydrogen peroxide (H2O2) in the presence of nickel(II) chloride (NiCl2). The effectiveness of this reaction was enhanced by L-histidine (His) which forms the Ni(II)-His2 complex. Similar effects of NiCl2 and His were observed on hydroxylation of pure dG with H2O2. The rate of pure dG conversion to 8-OH-dG at 37 degrees C (100 mM phosphate buffer) depended on combination and concentration of the reagents and on pH. Following 24 h incubation at pH 7.4 of 0.75 mM dG with 30 mM H2O2 and 1 mM NiCl2, dG was converted into 8-OH-dG to the extent of 0.05% in the absence of His and 0.45% in the presence of 2 mM His. After 24 h incubation at pH 7.4 of 0.5 mg/ml DNA with 7.5 mM H2O2 and 0.1 mM NiCl2, 0.18% of the dG moiety was converted into 8-OH-dG in the absence of His and 0.42% in the presence of 0.2 mM His. Interestingly, a mixture of H2O2 with His was also capable of oxidizing dG to 8-OH-dG even in the absence of NiCl2, albeit less effectively than in the presence of NiCl2. This effect was not suppressed after treatment of dG, His and the buffer with Chelex to remove divalent metal contaminants, if any. The exact chemistry of the observed phenomena remains to be determined. Since the Ni(II)-His2 complex is the major low mol. wt nickel carrier in mammalian organisms, the observed redox properties of this complex, reported here for the first time, may be crucial for the toxicity and carcinogenicity of nickel. PMID- 1740021 TI - The time-dependent increase in the binding of benzo[a]pyrene to DNA through (+) anti-benzo[a]pyrene-7,8-diol-9,10-epoxide in primary rat hepatocyte cultures results from induction of cytochrome P450IA1 by benzo[a]pyrene treatment. AB - The proportion and amount of benzo[a]pyrene (B[a]P) that binds to DNA through the carcinogenic (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide [(+)-anti-BPDE] increases with time of exposure to B[a]P in cell cultures derived from a number of species. Pretreatment of primary rat hepatocyte cultures for 12 h with 1 microgram B[a]P/ml medium increased the subsequent metabolism of [3H]B[a]P by 47% and [3H]B[a]P-DNA binding by 53% compared with acetone-pretreated hepatocytes. The amount of (+)-anti-BPDE bound to DNA in the B[a]P-pretreated hepatocytes increased 175%. B[a]P pretreatment also increased DNA-binding 2-fold in hepatocytes treated with [3H]7,8-dihydroxy-7,8-dihydro-B[a]P but had no effect on DNA binding in cells treated with anti-B[a]P-7,8-diol-9,10-epoxide. Western blotting showed that cytochrome P450IA1, which was not detectable prior to B[a]P treatment, was selectively increased by B[a]P treatment. A monoclonal antibody that specifically inhibits cytochrome P450IA1 reduced the binding of B[a]P to DNA by greater than 90% in microsomal preparations from B[a]P-pretreated hepatocytes. These results indicate that the time-dependent increase in the formation of (+) anti-BPDE-DNA adducts results from an increase in the amount and proportion of B[a]P metabolized to this ultimate carcinogen by P450IA1 that is induced by the B[a]P treatment. The importance of P450IA1 induction by the B[a]P for its activation to this ultimate carcinogenic metabolite suggests that long-term exposure of cells to B[a]P could result in activation of a higher proportion of the B[a]P to the carcinogenic (+)-anti-BPDE. PMID- 1740022 TI - Increased cytogenetic damage in smokers deficient in glutathione S-transferase isozyme mu. AB - Reduced expression of the mu-isozyme of glutathione S-transferase (GST; EC 2.5.1.18) has been associated with increased lung cancer risk. We studied the association between GST-mu expression and DNA damage as measured by sister chromatid exchanges (SCE) in healthy male smokers. SCE levels were higher in the 71 GST-mu-deficient smokers compared to the 83 non-deficient smokers (5.24 versus 4.97 SCE/lymphocyte; P = 0.09). In smokers having high plasma cotinine levels (greater than median of 315 ng/ml), this mu-related difference was more pronounced (5.50 versus 4.97; P = 0.01), whereas it was absent in smokers having low cotinine levels (4.95 versus 4.97; P = 0.92). Increased cytogenetic damage in GST-mu-deficient heavy smokers may thus explain the association between GST-mu expression and lung cancer. PMID- 1740023 TI - Defining conditions for the efficient in vitro cross-linking of proteins to DNA by chromium(III) compounds. AB - The formation of cross-links between bovine serum albumin and DNA in the presence of chromium(III) chloride was found to be highly pH dependent. In vitro, such lesions were only formed at acidic values of pH, but were not detected at neutral pH. Complexes of chromium(III) and GSH/GSSG similarly failed to induce DNA protein cross-links at physiological values of pH. Our findings indicate that the cross-links generated in vitro at acidic pH may not be directly relevant to the observed formation of such lesions in cultured cells and that a physiologically relevant in vitro model for the efficient cross-linking of proteins to DNA has yet to be devised. PMID- 1740024 TI - Repeated exposure to Opisthorchis viverrini and treatment with the antihelminthic Praziquantel lacks carcinogenic potential. AB - The effects of repeated Praziquantel administration, subsequent to infection and reinfection with Opisthorchis viverrini (OV), on lesion development in the Syrian hamster liver were investigated. Five applications of the antihelminthic drug were made (300 mg/kg body wt, i.g.), each time approximately 5 weeks after dosing with 60-80 OV metacercariae at weeks 0, 8, 16, 24 and 32. The animals were then maintained until week 40 when they were killed; histopathological investigation revealed no significant development of either hepatocellular of cholangiocellular preneoplastic/neoplastic lesions. The results indicate that repeated exposure to Praziquantel at levels sufficient for successful removal of parasite infestation does not itself carry carcinogenic risk. PMID- 1740025 TI - Changing the way we do business. PMID- 1740026 TI - Socializing nursing students into professional activities. PMID- 1740027 TI - Primary malignant localized fibrous tumours of the pleura: clinical, radiological and pathological features. AB - Localized fibrous tumours of the pleura are rare primary pleural tumours that may exhibit malignant behaviour in approximately 20% of cases. The clinical, radiological and pathological features of five patients with malignant localized fibrous tumours of the pleura are presented. Clinical symptoms included chest pain, breathlessness and cough. Hypertrophic pulmonary osteoarthropathy (HPOA) occurred in one patient. Chest radiographs and thoracic computed tomography (CT) demonstrated large necrotic masses, with focal calcification and compressive atelectasis of the underlying lung. Histological features were variable and resulted in designation of these tumours as localized fibrous tumours of the pleura of low or high grade malignancy. The grading of malignancy did not correlate with final outcome, adequacy of surgical excision being the most important factor. These tumours have been referred to as benign pleural fibromas or localized mesotheliomas, but these names are inaccurate and the term localized fibrous tumour of the pleura is to be preferred. This term should also include tumours such as malignant fibrous histiocytoma of the pleura. PMID- 1740028 TI - Complications attributable to the formation of the track in patients undergoing percutaneous nephrolithotomy. AB - Reported complication rates of percutaneous nephrolithotomy vary considerably. In our own experience of 110 percutaneous nephrolithotomies performed by an experienced interventional radiologist, the complication rate for the entire procedure was 3.6%, and for the formation of the nephrostomy track 0.9%. This compares favourably with the reports from the major centres. Radiation dose to the operator was monitored and our results confirm that with meticulous attention to technique, dosages may be kept very low. We conclude that prior training in interventional techniques is a major factor in reducing both the morbidity associated with percutaneous nephrolithotomy and the radiation dose to the operator. PMID- 1740029 TI - Intracranial extension of orbital pseudotumour. AB - Radiologically demonstrable intracranial extension of orbital pseudotumour is rare, and only four cases appear to have been reported previously in the literature. A review of the computed tomographic (CT) images of 90 biopsy proven cases of orbital pseudotumour seen over a 10 year period revealed eight cases with intracranial meningeal spread. PMID- 1740030 TI - Infratemporal pneumatocele arising from maxillary sinus. AB - Pneumatocele of the infratemporal fossa caused by herniation of air through a break in the wall of the aerated maxillary sinus is rare. Two cases are reported: one arising from a maxillary pneumocele with a defect in the wall of the zygomatic recess and one associated with maxillary radionecrosis with pathological fracture complicated by infection. Computed tomography can clearly demonstrate the extent of the pneumatocele, and can show the maxillary pathology and the causative bony defect in the sinus. Treatment depends on the clinical conditions of the patient, the pathology and the size of the bony defect. PMID- 1740031 TI - The involvement of the maxillary antrum by odontogenic keratocysts. AB - The involvement of the maxillary antrum by an odontogenic keratocyst is an unusual presentation of this important lesion which shows a tendency to recur following surgery when it arises in the mandible. The clinical presentation and radiological appearance in five patients are described. The differential diagnosis of this lesion is briefly reviewed. PMID- 1740032 TI - Technical report: interventional sialography--balloon dilatation of a Stensen's duct stricture using digital subtraction sialography. PMID- 1740033 TI - Technical report: a 'new' tube providing rapid insertion for the small bowel enema. AB - Small bowel enteroclysis (SBE) is considered to be diagnostically superior to the conventional barium follow through examination (Sanders and Ho 1976; Maglinte et al., 1982; Herlinger, 1982) and would be more generally acceptable if jejunal intubation could be undertaken rapidly with minimum fluoroscopy and patient discomfort. Using a modified Merck 'Coresafe' tube 75 out of 80 patients referred for SBE were intubated, with considerably reduced fluoroscopic and intubation times. No tube related difficulty was encountered and patient tolerance was good. PMID- 1740034 TI - Case report: multiple hepatic and pulmonary haemangioblastomas--a new manifestation of von Hippel-Lindau disease. AB - Capillary haemangioblastomas rarely occur outside the central nervous system and have not been described previously in the lung or liver. We describe such lesions developing in a patient with von Hippel-Lindau complex who previously had cerebellar and spinal haemangioblastomas resected. PMID- 1740035 TI - Pelvic radiation disease. PMID- 1740036 TI - Case report: the air crescent sign in pulmonary leukaemic infiltrate. AB - Localized pulmonary infiltrates in leukaemic patients were until recently almost synonymous with superinfection. This case illustrates that true leukaemic pulmonary involvement should always be considered in these patients when a high peripheral blast count is present. We believe this to be the first description of cavitation in a proven leukaemic infiltrate. PMID- 1740037 TI - Case report: replacement lipomatosis of the kidney--unusual CT features. AB - A case of replacement lipomatosis of the kidney (RLK) diagnosed on computed tomography (CT) is presented. CT demonstrated an infiltrating fatty mass surrounding a scarred kidney with a central staghorn calculus. Infiltration of the retroperitoneal muscles and an abscess within the erector spinae were also seen. The most important feature of this case is a mass effect causing displacement of the aorta and spleen, which is enlarged. This is usually only seen with malignant masses and has not been previously reported with RLK. The literature and radiological features of RLK are reviewed. PMID- 1740038 TI - Case report: deep venous thrombosis following iopamidol venography. AB - A case of deep venous thrombosis following iopamidol venography is presented. This complication has not previously been reported. PMID- 1740039 TI - Case report: broken intracholedochal stent. AB - Decompression of biliary obstruction by an internal stent is well accepted in patients with malignant strictures. Less frequent is the use of this technique for the management of benign disorders. In the latter situation the biliary stent may be left in place for a very long period. We report a rare complication of a broken intracholedochal stent which had been inserted for a benign post-operative stricture. PMID- 1740040 TI - Orbital pseudotumour. PMID- 1740041 TI - Hepatic and splenic calcification due to amyloidosis. PMID- 1740042 TI - The value of negative needle biopsy in suspected operable lung cancer. PMID- 1740043 TI - Polyamide--the evolution of a synthetic membrane for renal therapy. PMID- 1740044 TI - Basic features of the polyamide membranes. AB - Progress in membrane and membrane process development have contributed to the continuous improvement of the extracorporeal treatment of renal failure during the last 40 years. Today membranes can be adapted to the specific needs required by their clinical application. Synthetic structures like the polyamide membranes offer a wide range of possibilities in performance and hemocompatibility, due to: (1) the use of block polymers or polymer blends and mixtures, and (2) modification of membrane structure, pore size and porosity, due to changes of the preparation process. However, further improvements are still required to achieve the ultimate goal of matching the performance of biological membranes. PMID- 1740045 TI - High-flux hemodialysis with a polyamide dialyzer. PMID- 1740046 TI - Continuous renal replacement therapies of acute renal failure and the polyamide membrane. PMID- 1740047 TI - Dialysis-related amyloidosis and high-flux membranes. PMID- 1740048 TI - Removal of high-molecular-weight toxins. PMID- 1740049 TI - Biocompatibility of the polyamide membranes. PMID- 1740050 TI - Pyrogen retention by the polyamide membranes. PMID- 1740051 TI - Hemofiltration in the past and present. PMID- 1740052 TI - Hemofiltration: predilution versus postdilution. PMID- 1740053 TI - Hemodiafiltration: technical aspects. PMID- 1740054 TI - The polyamide membrane in hemodiafiltration. PMID- 1740055 TI - Mastitis: why is it so hard to cure? PMID- 1740056 TI - Bovine endometritis: the burden of proof. PMID- 1740057 TI - A comparison of end-tidal halothane concentrations measured at proximal and distal ends of the endotracheal tube in the horse. AB - Measurements (n = 126) of end-tidal halothane concentrations were taken from 21 horses anesthetized for routine and emergency surgery. One hundred five paired values allowed comparison of gas samples taken near the oral end of the endotracheal tube (Y1) to samples obtained at the cuffed end of the endotracheal tube (Y2). Twenty-one paired readings were assessed to compare samples taken 25 cm beyond the cuffed end of the tube (Y3) to samples from Y1. Measurements were made at all locations at 15-minute intervals starting 30 minutes after beginning halothane. All measurements were made in triplicate at end-expiration, and both sites were sampled within 1 minute of each other. Halothane concentration was measured by rapid infrared analysis with a gas sampling rate of 150 ml/min and displayed as a digital reading. Calibration of the machine was checked regularly. The difference between readings (Y1-Y2 or Y1-Y3 = Sdif) was tested using general linear models and a significance level of p less than 0.05 was used. The variable Sdif was analyzed with respect to time, mode of ventilation, and type of recumbency; no effects of these variables were detected. The mean values (+/- SD) of 105 readings for Y1 and Y2 were 2.41 vol% (+/- 0.49) and 2.39 vol% (+/- 0.49) respectively, and the Pearson's correlation coefficient (Y1 vs Y2) was 0.96. The mean values (+/- SD) of 21 measurements for Y1 and Y3 were 2.31 vol% (+/- 0.27) and 2.32 vol% (+/- 0.28) respectively and the Pearson's correlation coefficient (Y1 vs Y3) was 0.98. PMID- 1740058 TI - Mastitis due to Mycoplasma in the state of New York during the period 1972-1990. AB - Between January 1972 and December 1990, bulk-tank (n = 721) and cow (n = 9,163) milk samples from dairy herds in New York State were examined by bacteriologic procedures for Mycoplasma. The organism was found in 165 herds in 42 counties, and in 2.3 and 11.7% of the tank and cow samples, respectively. Mycoplasma bovis was isolated in 164 herds, M. californicum was isolated in 1. Highest incidence of mycoplasmal clinical mastitis occurred during the winter. The disease resulted in culling of 30-70% of the cows in several herds. Eighty-six of the positive herds were located in the western part of the state. This area had more large herds (greater than 200 cows) compared to the rest of the state; however, herd size was not a risk factor. Purchased animals added to herds without quarantine, poor hygiene during mastitis treatment, and personnel in contact with mastitic cows or infected milk were involved in outbreaks and disease transmission. PMID- 1740059 TI - Characterization of Sarcocystis neurona from a thoroughbred with equine protozoal myeloencephalitis. AB - Morphological information is presented for syntype material of the etiologic agent of equine protozoal myeloencephalitis, Sarcocystis neurona. A clinical description of the horse from which the organism was isolated and the methodology used to immunosuppress the horse in an attempt to increase parasite numbers are also given. The description includes microscopic details observed both with light and transmission electron microscopy. Mainly stages from tissue are illustrated, but information is also presented on the development of the organism after inoculation onto monolayers of bovine monocytes. It is believed that the large numbers of organisms observed in this horse were due to its having not received prior treatment with trimethoprimsulphonamide and the large amounts of corticosteroids that were administered in order to facilitate isolation of the pathogen. PMID- 1740060 TI - Nonsteroidal management of canine pruritus with amitriptyline. AB - Thirty-one dogs with nonlesional pruritus were treated with amitriptyline (1 mg/kg orally q12h) to determine its efficacy in the management of canine allergic pruritus. Seventeen dogs were known to be atopic, 8 were presumed to be atopic, and 6 had pruritus of undetermined etiology. Pruritus was virtually eliminated in 5 (16.1%) dogs, reduced by approximately 50% in another 5 (16.1%) dogs, and not changed in the remaining 21 dogs. Side effects were uncommon. PMID- 1740061 TI - Attempted reinnervation of the equine larynx using a muscle pedicle graft. AB - Laryngeal hemiplegia was induced in 4 ponies via a left recurrent laryngeal neurectomy. Reinnervation of the denervated left cricoarytenoideus dorsalis muscle was then attempted using a muscle pedicle graft from the right cricoarytenoideus dorsalis muscle. In 3 ponies there was no return of abductor function and failure of graft survival. In the fourth pony there was return of abductor function along with survival of the muscle bridge, however, there was evidence of reinnervation across the neurectomy site. Muscle-to-muscle neurotization of the paralyzed equine larynx, utilizing the cricoarytenoideus dorsalis muscle, does not appear to be a clinically useful technique. PMID- 1740062 TI - Serum concentrations of cefepime (BMY-28142), a broad-spectrum cephalosporin, in dogs. AB - Serum concentrations of cefepime (BMY-28142) were determined for four dosing regimes, 10 mg/kg or 20 mg/kg, given as single subcutaneous (SC) or intramuscular injections (IM) to dogs. Serial serum samples were analyzed for the presence of cefepime by high-performance liquid chromatography. In experiment 1, the overall mean (+/- SEM) serum concentration (for a 12-hour period) after a dose of 20 mg/kg for SC and IM routes (4.9 +/- 0.74 micrograms/ml and 5.5 +/- 0.63 micrograms/ml, respectively) was twice that for the 10 mg/kg dose given either SC or IM (2.2 +/- 0.31 micrograms/ml and 2.8 +/- 0.47 micrograms/ml, respectively). There was no significant difference (p greater than 0.05) in mean serum concentrations for SC and IM routes of administration at the same dosage. In subsequent experiments, 5 doses of cefepime (20 mg/kg) were administered IM at 12 hour (experiment 2) or 24-hour (experiment 3) intervals. The mean (+/- SEM) peak serum concentration was 12.1 +/- 1.59 micrograms/ml, 2 hours after the 2nd injection in experiment 2. In experiment 3, the mean (+/- SEM) peak serum concentration was 10.9 +/- 1.34 micrograms/ml, 4 hours after the 1st injection. Mean trough concentrations in experiment 2 were greater than or equal to 0.5 microgram/ml and less than or equal to 0.5 in experiment 3. Multiple IM doses produced transient edema at the injection site and mild lameness in all dogs. Cefepime was highly active against single canine isolates of Staphylococcus intermedius, Pseudomonas aeruginosa and Escherichia coli, with minimum inhibitory concentrations of 0.125 microgram/ml, 1 microgram/ml and 0.3 microgram/ml, respectively. PMID- 1740063 TI - Equine coxofemoral luxations: 17 cases (1975-1990). AB - The medical records of 17 horses with coxofemoral luxation were examined. Ponies and miniature horses were overrepresented. The mean age at the time of diagnosis was 7 years (range 1 month to 25 years). Seventy percent were female. Severe trauma, such as a fall or being kicked by another horse, was a common etiology. Thirty-five percent had other orthopedic injuries associated with the luxation. Closed reduction, with the use of a mechanically assisted calving device, was attained in 5 cases but reluxation occurred shortly afterward in 4 of these. Varying surgical techniques were used in 3 cases but none were successful in maintaining reduction. Ponies and miniature horses are better able to handle chronic lameness and therefore had a better long-term survival rate than horses with a chronically luxated coxofemoral joint. PMID- 1740064 TI - Hematuria and weight loss in a mare with pancreatic adenocarcinoma. AB - This clinical report describes an 11-yr-old Thoroughbred mare that presented with clinical signs of weight loss and hematuria. History and clinical findings suggested the mare had neoplasia of the urogenital system. Although ultrasound guided biopsy of the perirenal mass did not yield abnormal cells, large irregular cells were isolated from the thoracic and peritoneal fluid. At necropsy, multiple firm nodules were disseminated throughout the peritoneal cavity. Histological examination of the nodules revealed cells that were consistent with a pancreatic exocrine adenocarcinoma. This is the first report of pancreatic adenocarcinoma causing dysfunction of the urogenital system. PMID- 1740065 TI - Prospective, randomized trial of inpatient vs. outpatient bowel preparation for elective colorectal surgery. AB - A prospective, randomized trial of inpatient vs. outpatient bowel preparation for elective colorectal surgery was performed in 100 consecutive patients. Bowel preparation was standardized for both groups and consisted of 4 liters of Colyte (Reed & Carnrick, Piscataway, NJ) and oral neomycin and Flagyl (G. D. Searle & Co., Skokie, IL) the day before surgery. Patients were randomized into four subcategories: ileocolostomy, colocolostomy, abdominal perineal resection, and other. Tap water enemas were administered on the morning of surgery to ensure and adequate mechanical preparation. Ninety-six percent of the inpatient group and 97 percent of the outpatient group were able to drink three-fourths or more of the oral lavage preparation (P = 0.789, Fisher's exact text). A mean of 2.26 tap water enemas was required to achieve clear returns for the inpatient group, compared with 2.28 tap water enemas for the outpatient group (P = 0.221, Fisher's exact test). The adequacy of the bowel preparation as graded by the primary surgeon was good (84 percent), fair (12 percent), and poor (4 percent) in the outpatient group (P = 0.673, Fisher's exact test). Wound infection developed in 4 percent of the inpatient group and 4 percent of the outpatient group (P = 1.0, Fisher's exact test). Anastomotic leak of intra-abdominal abscess was seen in one patient in each group (P = 1.0, Fisher's exact test). We conclude that outpatient bowel preparation is as effective as inpatient bowel preparation for elective colorectal surgery and offers the advantage of cost savings and shorter hospitalization. PMID- 1740066 TI - Clinical conundrum of solitary rectal ulcer. AB - A retrospective study of 80 patients with biopsy-proven solitary rectal ulcer (SRU) was conducted to review its clinical spectrum. The median follow-up was 25 months. The female-to-male ratio was 1.4:1.0, and the mean age was 48.7 years (range, 14-76 years). Principal symptoms were bowel disturbances (74 percent) and rectal bleeding (56 percent). Twenty-one patients (26 percent) were asymptomatic and required no treatment. A previous "wrong" diagnosis was made in 25 percent. Rectal prolapse was identified in 28 percent (full-thickness, 15 percent; mucosal, 13 percent). The macroscopic appearance of the lesion seen in SRU varied widely and included polypoid lesions in 44 percent (the predominant finding in the asymptomatic group), ulcerated lesions in 29 percent (always symptomatic), and edematous, nonulcerated, hyperemic mucosa in 27 percent. Anorectal manometry provided little helpful information in the patients in whom it was performed. Management by bulk laxatives and bowel retraining led to symptomatic improvement in 19 percent of cases. In 29 percent of cases, symptoms persisted despite endoscopic healing of the lesion. Intractability of symptoms led to surgery in only 27 (34 percent) patients. Depending on the presence or absence of rectal prolapse, rectopexy or a conservative local procedure (such as local excision), respectively, appeared to be the optimal surgical treatment. The polypoid variety tended to respond to therapy more favorably than non-polypoid varieties. Thus, the macroscopic appearance of SRU has a significant bearing on the clinical course, and most cases do not require surgery. PMID- 1740067 TI - Videoproctography in selecting patients with constipation for colectomy. AB - The results of colectomy for constipation based only on evidence of delayed colonic markers have been disappointing. The operation may fail because these patients are unable to evacuate the rectum owing to outlet obstruction. In the present study, we have used a combination of videoproctography and transit marker studies in an attempt to predict patients who will have a favorable outcome after colectomy by excluding patients with outlet obstruction. Videoproctography was performed in 228 patients referred for consideration of surgery for constipation. Only 111 (38 percent) had a normal proctogram with complete evacuation of liquid barium. Of these 111 patients, 21 (19 percent) had delayed colonic marker studies. Colectomy and ileorectal anastomosis were performed in 18 of these 21 patients; two years later, 16 were symptom free, with a median daily bowel frequency of four (range, two to six). The remaining two patients failed to respond to surgery. These data suggest that true idiopathic, slow-transit constipation is uncommon, but, when identified on the basis of delayed markers and the ability to expel liquid on proctography, an excellent result can be anticipated from colectomy and ileorectal anastomosis. PMID- 1740068 TI - Malignant cells are collected on circular staplers. AB - Anastomotic recurrence after resection of colorectal carcinoma has been attributed to insufficient clearance, migration of tumor cells into lymphatics, or implantation of exfoliated malignant cells during anastomosis. We studied 10 patients submitting to low anterior resection for cancer 6 to 16 cm (mean, 12.6 cm) from the anal verge. The anastomosis was performed with a circular stapler introduced transanally into the rectum using the established technique. No lavage of the rectal stump with a cytotoxic agent was conducted before the anastomosis was performed. Having completed the anastomosis, the stapler and the doughnuts were washed with saline, which was collected for cytologic examination. The doughnuts were then examined histologically; all were tumor free. In 9 of the 10 cases, malignant cells were identified in the centrifuged saline. It may be that malignant cells collected by the stapler are implanted during anastomosis and cause subsequent anastomotic recurrence. PMID- 1740069 TI - Chronic constipation with encopresis persisting beyond 15 years of age. AB - Childhood constipation with encopresis is a common malady. Previous reports suggest that essentially all patients either respond to standard treatments or have spontaneous recovery before 16 years of age. In this paper, we describe the results of anorectal function studies and treatment outcome in four patients in whom constipation and encopresis persisted beyond 15 years of age. Abnormalities in the ability to defecate water-filled balloons, in external sphincter relaxation with straining, in rectal sensation and development of the urge to defecate, and in maximum anal resting pressure were seen in some or all of these patients. In addition, two patients had impaired voluntary squeeze strength. Two patients responded to standard therapy; a colostomy was needed in one; and one failed therapy and has become a recluse. PMID- 1740070 TI - Colorectal cancer risk after jejunoileal bypass: dysplasia and DNA content in longtime follow-up of patients operated on for morbid obesity. AB - Jejunoileal bypass (JIB) has been a widespread operation for treatment of morbid obesity. Bile acids are regarded as cofactors in the carcinogenesis of the colon, and, since intestinal bypass involves increased exposure of bile acids to the large intestinal mucosa, JIB has been postulated to increase the risk for colorectal carcinoma. In experimental studies on animals, the results have indicated an increased frequency of induced carcinomas, but in clinical series only one patient with colon carcinoma has been reported. Thirty women, operated on with JIB 11 to 17 years earlier, were examined by colonoscopy with multiple biopsies, systematically taken for histologic evaluation and flow cytometric DNA analysis. In only one patient, low-grade dysplasia was detected in an initial adenomatous lesion but was not visible macroscopically. No DNA aneuploidy was found. In a control group of 11 patients examined for non-neoplastic disease, neither dysplasia nor aneuploidy was diagnosed. Within 17 years postoperatively, we have, by these methods, not been able to verify any colorectal malignant transformation in patients operated on with JIB. However, since carcinogenesis is a long process, further surveillance will be demanded before an increased risk for colorectal carcinoma can be excluded. PMID- 1740071 TI - Fibrin glue improves the healing of irradiated bowel anastomoses. AB - Many surgeons are reluctant to construct a bowel anastomosis with irradiated intestine. Previous studies have demonstrated diminished tensile strength of rat small bowel anastomoses that have been irradiated intraoperatively. To determine whether fibrin glue, a known tissue adhesive, improves the healing of these anastomoses, 69 male Sprague-Dawley rats were randomized into three anastomotic groups: Group 1, sutured ileal anastomosis without radiation or fibrin glue; Group 2, irradiated sutured ileal anastomosis without fibrin glue; and Group 3, irradiated ileal anastomosis with fibrin glue added to the suture line. Groups 2 and 3 received a single dose of 2,000 R intraoperatively. At seven days, the rats were sacrificed and the anastomotic segment was tested for breaking (tensile) strength. Anastomotic collagen content was evaluated using a hydroxyproline assay. Tensile strength results demonstrated that Group 2 was significantly weaker than Groups 1 and 3 (P = 0.001) and that the hydroxyproline content of Group 3 was significantly greater than that of Group 2 (P = 0.015). These results show that the addition of fibrin glue to an intraoperatively irradiated small bowel anastomosis improves healing, as demonstrated by both tensile strength and hydroxyproline content studies. PMID- 1740072 TI - Can Hemoccult-II replace colonoscopy in surveillance after radical surgery for colorectal cancer and after polypectomy? AB - Surveillance after colorectal carcinoma and adenoma includes colonoscopy, which is a demanding procedure for the patient, doctor, and society. Therefore, it was investigated whether a simple fecal occult blood test could replace colonoscopy. Hemoccult-II (H-II) was performed before 1,244 colonoscopies in patients with previous cancer and before 328 colonoscopies in an adenoma surveillance program. The H-II test was positive in 3 of 9 patients with local recurrence, in 2 of 13 with metachronous cancer, and in 31 of 186 with adenomas. The test was positive more often in patients with large and multiple adenomas, sigmoid adenomas, and adenomas with villous elements and moderate-to-severe dysplasia, but the sensitivity did not reach more than 25 to 40 percent. It was concluded that markers more sensitive than H-II are needed to detect metachronous cancers and new adenomas. In the meantime, colonoscopy has to be used with intervals of several years, but not for detection of local recurrent cancer, which in most cases may be found by simpler means. PMID- 1740073 TI - Carcinoma of the rectal pouch following restorative proctocolectomy. Report of a case. AB - A case of adenocarcinoma developing in the pouch following restorative proctocolectomy is presented. This seems to be the third reported in the literature. The carcinoma developed from the remnants of precancerous rectal mucosa left in the muscular rectal cuff. The patient had been suffering from ulcerative colitis for 17 years prior to the development of the malignancy. He presented with features of subacute intestinal obstruction. Diagnosis was by sigmoidoscopic examination of the pouch and biopsy. He was treated with abdominoperineal resection of the pouch and rectum, followed by chemotherapy. PMID- 1740074 TI - Malignant histiocytosis of the intestine simulating Crohn's disease. Report of a case. AB - We report a case of malignant histiocytosis of the intestine (MHI) in which clinical and small bowel barium examination led to an initial diagnosis of Crohn's disease. The patient's symptoms and radiologic features improved dramatically with steroid therapy, and the patient remained free of severe symptoms for five years; at this stage, massive rectal bleeding occurred and segmental ileal resection was performed. Pathology findings of the resected specimen revealed nonspecific ulceration of the ileum. The correct diagnosis, MHI, became apparent six months after surgical intervention, on the appearance of multiple lymphadenopathy. PMID- 1740075 TI - Spontaneous perforating hematoma of the rectum. Report of a case. AB - Intramural hematomas of the intestine most often occur in the setting of blunt abdominal trauma. However, spontaneous hematomas can occur secondary to either hematologic disorders, or use of anticoagulant therapy. There has been no clearly documented report of a spontaneous rectal hematoma. We describe the novel treatment of a patient with a spontaneous intramural hematoma of the rectum which presented as an abdominal catastrophe. PMID- 1740076 TI - Leon Ginzburg 1899-1988. The road to regional enteritis. 1974. PMID- 1740077 TI - Practice parameters for antibiotic prophylaxis to prevent infective endocarditis or infected prosthesis during colon and rectal endoscopy. The American Society of Colon and Rectal Surgeons. PMID- 1740078 TI - Practice parameters for antibiotic prophylaxis--supporting documentation. The Standards Task Force. American Society of Colon and Rectal Surgeons. PMID- 1740079 TI - Data on hepatic metastases. PMID- 1740080 TI - Progress in the development of the Canadian Society of Colon and Rectal Surgeons. PMID- 1740081 TI - The prevalence of confusion in the definition of hemorrhoids. PMID- 1740082 TI - Common nursing diagnoses for pulmonary alveolar edema patients. AB - PAE can occur as a consequence of heart failure. Depending upon the extent of left ventricular failure, pulmonary edema can vary widely in severity. To anticipate potential health care needs and, ultimately, to treat PAE, the critical care nurse identifies common nursing diagnoses. Once the nurse understands the physiologic or psychological mechanisms for the particular nursing diagnoses, he or she can serve as a reference point to identify expected nursing outcomes. PMID- 1740083 TI - Effectiveness of coping strategies among critical care nurses. AB - Although research on job stress has focused on the extent or causes of stress in critical care, few studies have focused on the effects of stress reduction strategies by the critical care staff. The results of a study that examined the strategies critical care nurses used to manage job stress and the effectiveness of these techniques are described. PMID- 1740084 TI - The ethical case analysis: heroic measures for patients with chronic problems. Part I: The ethical case. PMID- 1740085 TI - The ethical case analysis: heroic measures for patients with chronic problems. Part II: Ethical analysis. PMID- 1740086 TI - Nursing outcomes: focusing on results. PMID- 1740087 TI - Durable power of attorney: nursing implications. AB - Written, witnessed advance directives such as Durable Powers of Attorney and Living Wills communicate patients' care preferences. The critical care nurse must be knowledgeable about these legal documents to be able to effectively uphold the specific care requests. The authors define advance directives and outline the role of the nurse in execution of these directives. PMID- 1740088 TI - Self-care assessment: key to teaching and discharge planning. AB - Patient education research supports the premise that the nurse must consider the patient's perspective before attempting to provide an educational program for implementing the therapeutic regimen. This article describes how a self-care assessment instrument can help the nurse to develop an individualized teaching plan for the cardiac patient. PMID- 1740089 TI - Imagery: helping ICU patients control pain and anxiety. AB - As healthcare providers strive for holistic approaches to modern problems, the use of imagery and relaxation is gaining popularity. Relaxation and imagery can be used effectively in critical care areas to help patients cope with their symptoms, treatments, and/or the critical care environment. PMID- 1740090 TI - Assessing congenital heart defects in the cocaine-exposed neonate. AB - An estimated 100,000 "crack babies" are born each year in the United States. Because in addition to a variety of other congenital anomalies, neonatal cardiac defects have recently been linked to maternal cocaine use, the critical care nurse needs to conduct a detailed cardiac status assessment on all cocaine exposed infants. PMID- 1740091 TI - Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. AB - Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects than in any comparison group except those with clinical SLE. The number of subjects with 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers greater than 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r2 = .0205 (p less than 0.036) in women and this correlation was almost statistically significant in men cc = .1282, r2 = .0253 (p less than 0.059). In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erythematosus as perceived by the ARA score and the increased FANA titers. PMID- 1740092 TI - Activation of cerebral dopaminergic systems by noise and whole-body vibration. AB - To clarify the involvement of the central nervous system in responses of organisms to noise and whole-body vibration, the activity of dopamine (DA) neuron systems was estimated by examining DA turnover rates in various discrete regions of the brains of rats exposed to noise (broad band, 102 dB) or whole-body vibration (20 Hz, 4G) for 90 min. Plasma corticosterone level (COR) was determined simultaneously as an index of stress-induced autonomic-nervous and endocrine functions. Noise and whole-body vibration increased both COR and DA turnover rates (shown by an increase of homovanillic acid (HVA) and/or HVA/DA ratio) in the frontal cortex (FC) and the nucleus accumbens (NAc). Only noise increased the DA turnover rate in the amygdala (AMY). Furthermore, strong positive correlations of the HVA/DA ratios in the FC and the NAc with COR were observed in rats exposed to noise or vibration. These results suggest that the responses of organisms to noise and whole-body vibration may be critically mediated by cerebral DA systems, in particular by the mesocortical DA system, indicating that change of DA in the AMY can be considered a specific response to noise. PMID- 1740093 TI - The reversibility of tributyltin-induced toxicity in vitro as a function of concentration and duration of exposure (C x T). AB - The toxicity exhibited by murine erythroleukemic cells (MELC) exposed to tributyltin (TBT) is a function of both concentration (C) and duration of exposure (T). At or above a critical C x T product value (CPV) (e.g., 0.5-1.0 microM TBT, 6 hr), exposed MELC exhibit severe, irreversible toxicity: decreased membrane integrity (viability, measured by propidium iodide [PI] exclusion), grossly perturbed cell-cycle distributions, and fixation of the plasma membrane/cytoplasm complex. Below the CPV, exposed cells exhibit retention of carboxyfluorescein (CF) fluorescence (indicative of decreased plasma membrane permeability) and decreased cell proliferation, a result of retardation of progression into, through, and out of the S (DNA synthetic) phase of the cell cycle. However, following washout and recovery, mean CF fluorescence, cell proliferative capacity, and cell-cycle kinetics return to control levels. These results suggest that the toxic changes induced by TBT exposure may be reversible if exposure conditions do not exceed the CPV. To assess whether the CPV has been exceeded, a multiparameter flow cytometric analysis of membrane integrity and cell-cycle kinetics is useful. PMID- 1740094 TI - Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse: long-term oral administration of several manganese compounds. AB - This work has identified the relative toxicity of four forms of manganese, using biogenic amine levels, tissue retention, weight gain, and activity scores as criteria. Male mice were chronically treated with four forms of manganese administered orally, mixed with the diet, for 12 months. The food intake for the control mice and the mice exposed to manganese was similar, but the manganese treatment reduced normal weight gain in the mice. The Mn levels were higher in some parts of brain after feeding insoluble salts than after the soluble salts. The concentration of manganese was significantly increased in the liver and spleen of the manganese carbonate-exposed group, compared with the concentration in the control group. Manganese dioxide feeding lowered dopamine and increased homovanilic acid. Since manganese dioxide is a powerful oxidizing agent in organic chemistry, it possibly enhanced the oxidative metabolite of dopamine. Accumulation of manganese in the brain correlated with reduced hypothalamic dopamine levels in the manganese acetate-exposed group; and the amount of manganese accumulated correlated with the intensity of suppression of motor activity. These findings indicate that manganese dioxide is more toxic than divalent manganese. Of the divalent manganese compounds, manganese acetate seemed to have the greatest toxic effect. PMID- 1740095 TI - Morphometric, structural, and ultrastructural studies of tench (Tinca tinca L.) hepatocytes after copper sulfate administration. AB - A structural, ultrastructural, and morphometric study was made of the liver parenchyma of 12 adult tench (Tinca tinca, L.) subjected to acute experimental copper sulfate poisoning. The lesions observed were characterized by the accumulation in the cytoplasm of large amounts of hemoglobinemic pigment produced by intense hemolysis, initially in Kupffer cells and by the last stage of the experiment in hepatocytes. This process became increasingly severe, and culminated in the massive necrosis of large areas of liver parenchyma, which led to the death of tench 12 days after the start of the experiment. PMID- 1740096 TI - Ultrastructural changes induced by benzo[a]pyrene in sea bass (Dicentrarchus labrax) liver and intestine: importance of the intoxication route. AB - The ultrastructural effects of benzo[a]pyrene (BaP) on sea bass (Dicentrarchus labrax) liver and intestine were studied after experimental intoxication by two different routes: intraperitoneal injection and force-feeding. In both hepatocytes and enterocytes, the main structural perturbations concerned a large development of both rough and smooth endoplasmic reticulum and a great increase in the number of vacuoles and lysosomes in BaP-treated fish. After 17 days of contamination, some nuclear changes were observed, indicating the high reactivity of BaP metabolites which form covalent adducts with DNA and the long-term toxicity of this compound. However, in the intestine, after force-feeding intoxication, more perturbations were seen, particularly concerning the mitochondria. Both organs were altered in a different way with respect to the intoxication route. In BaP intraperitoneal injected fish, the liver was the first injured organ and presented heavier injuries than intestine. In force-feeding treated fish, the intestinal epithelium was the first concerned tissue and it was highly modified after BaP intoxication. The importance of the intoxication pathway in the effects of BaP on liver and intestine was discussed with special reference to their role in BaP uptake, metabolism, and distribution in the organism. PMID- 1740097 TI - Interactions of plant zinc and plant species on the bioavailability of plant cadmium to Japanese quail fed lettuce and spinach. AB - Many cadmium-contaminated environments contain high levels of zinc. The effects of plant Zn and plant species on plant Cd bioavailability were tested in Japanese quail fed lettuce and spinach. Four groups of birds received 10% of their diets as lettuce or spinach leaves intrinsically labeled with 109Cd and containing low or high intrinsic Zn. Two other groups were fed control diets containing 109Cd as CdSO4 and low or high Zn as ZnCO3. Cadmium concentrations in diets ranged from 0.857 to 1.05 micrograms/g dry wt. Zinc concentrations in low-Zn diets ranged from 21.2 to 22.8, and in high-Zn diets from 56.0 to 63.3 micrograms/g dry wt. Increased lettuce and spinach Zn decreased plant Cd retention in kidney, liver, and jejunum-ileum of Japanese quail. Spinach Cd was less absorbed than lettuce Cd at both Zn levels. Inorganic Zn produced a lesser decrease in Cd retention in kidney, liver, and jejunum-ileum than did plant Zn. We conclude that (1) crops that transport Zn and Cd readily into edible tissues show lower Cd bioavailability when grown in Zn-Cd contaminated environments than in Cd-only polluted sites, (2) plant species differ in Cd bioavailability for identical concentrations of Zn and Cd in edible tissues, and (3) toxicological studies with animals exposed to Cd salts and Zn supplements do not assess Cd bioavailability of Zn-Cd contaminated crops. PMID- 1740098 TI - Characteristics of the inhibition of interferon-alpha/beta production after crystalline nickel sulfide exposure. AB - Murine L-929 cells were treated with crystalline nickel sulfide (NiS), washed, and then exposed to polyriboinosinic-polyribocytidylic acid (Poly I:C) to induce interferon-alpha/beta (IFN-alpha/beta). Addition of crystalline NiS at different time points, from 24 hr prior to IFN induction (pretreatment) up to 12 hr after IFN induction, resulted in significant inhibition of IFN-alpha/beta production. In addition, 24-hr pretreatment of L-929 cells with crystalline NiS resulted in significantly decreased production of IFN-alpha/beta even 120 hr after addition of IFN inducer. IFN-alpha/beta at a known concentration was titered by means of a viral plaque reduction assay in crystalline NiS-treated L-929 cell cultures. Crystalline NiS did not show a significant inhibitory effect on the antiviral activity of IFN on L-929 cells as compared to controls. The results described here suggest that NiS has a rapid and a long-lasting inhibitory activity on the production of IFN-alpha/beta. PMID- 1740099 TI - In vitro effect of mercury on enzyme activities and its accumulation in the first trimester human placenta. AB - The effect of incubating young placental explants with HgCl2 on the activities of aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme), quinone reductase (QR), catecholamine-O-methyltransferase (COMT) (both phase II enzymes), and glucose-6 phosphate dehydrogenase (G-6-PD) is described. Mercury (Hg) at low doses significantly elevated placental phase I and phase II enzyme activities, but decreased the activity of G-6-PD. The increase in activities, which was time- and dose-dependent, was higher in explants incubated for 24 hr than in those incubated for 6 hr. The decrease in placental G-6-PD activity was drastic at low Hg dose levels but at higher levels the inhibitory effect was milder for both incubation periods. Placental explants accumulated Hg in amounts proportional to its concentration in the incubation medium and this accumulation was greater in explants incubated for 24 hr. The data suggest that contamination with low Hg levels from the environment during pregnancy may affect placental enzymatic activity. The accumulation of Hg during short incubation indicates a strong placental cell affinity for Hg, which could affect its other metabolic functions. The system used in sensitive, as it shows alteration in enzyme activity even with relatively low concentrations of the metal and the response is dose-related. PMID- 1740100 TI - Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster. AB - Mutations in the disconnected (disco) gene act to disrupt neural cell patterning in the Drosophila visual system. These mutations also affect adult locomotor activity rhythms, as disco flies are arrhythmic under conditions of constant darkness (DD). To determine the state of the circadian pacemaker in disco mutants, we constructed with pers double mutants (a short period allele of the period gene) and assayed their behavioral rhythms in light-dark cycles (LD), and their biochemical rhythms of period gene expression under both LD and DD conditions. The results demonstrate that disco flies are rhythmic, indicating that they have an active circadian pacemaker that can be entrained by light. They also suggest that disco mutants block or interfere with elements of the circadian system located between the central pacemaker and its outputs that mediate overt rhythms. PMID- 1740101 TI - Coordinate genetic control of yeast fatty acid synthase genes FAS1 and FAS2 by an upstream activation site common to genes involved in membrane lipid biosynthesis. AB - A systematic search for upstream controlling elements necessary for efficient expression of the yeast fatty acid synthase genes FAS1 and FAS2 revealed identical activation sites, UASFAS, in front of both FAS genes. The individual element confers, in a heterologous yeast test system, an approximately 40-fold stimulation of basal gene expression. The UASFAS motifs identified have the consensus sequence TYTTCACATGY and function in either orientation. The same sequence motif is found in the upstream regions of all so far characterized yeast genes encoding enzymes of phospholipid biosynthesis. In gel retardation assays, a protein factor, Fbf1 (FAS binding factor), was identified which interacted with UASFAS. The UASFAS motif proved to be an inositol/choline responsive element (ICRE) conferring strict repression by exogenous inositol and choline on a heterologous reporter gene. Its core sequence perfectly matches the CANNTG motif typical of basic helix-loop-helix DNA-binding proteins. In contrast to the individual UASFAS element, the intact yeast FAS promoters are not significantly influenced by inositol and choline, and thus allow nearly constitutive fatty acid synthase production. Available evidence suggests that additional cis- and trans acting elements, other than UASFAS and Fbf1, are involved in this constitutive FAS gene expression. PMID- 1740102 TI - Regulation of transcription of immunoglobulin germ-line gamma 1 RNA: analysis of the promoter/enhancer. AB - Antibody class switching is achieved by recombinations between switch (S) regions which consist of tandemly repeated sequences located 5' to Ig heavy chain constant (CH) region genes. RNA transcripts from specific unrearranged or germ line Ig CH genes are induced in IgM+ B cells prior to their undergoing class switch recombination to the same CH genes. Thus, the antibody class switch appears to be directed by induction of accessibility, as assayed by transcription of germ line CH genes. For example, IL-4 induces transcripts from the mouse germ line C gamma 1 and C epsilon genes to which it also directs switch recombination. We report here that the 150 bp region upstream of the first initiation site of RNA transcribed from the murine germ-line C gamma 1 gene, contains promoter and enhancer elements responsible for basal level transcription and inducibility by anti-Ig phorbol myristate acetate (PMA) and for synergy of these inducers with IL 4 in a surface IgM+ B cell line, L10A6.2 and a surface IgG2a+ B cell line, A20.3. Linker-scanning mutations demonstrated that multiple interdependent elements are required for inducibility by PMA and also for synergy with IL-4. Within the 150 bp region are several consensus sequences that bind known or putative transcription factors, including a C/EBP binding site--IL-4 responsive element, four CACCC boxes, a PU box, a TGF beta inhibitory element (TIE), an alpha beta interferon response element (alpha beta-IRE) and an AP-3 site. The relationship between transcription regulated by these elements and the regulation of endogenous germ-line gamma 1 transcripts and switching to IgG1 is discussed. PMID- 1740103 TI - The TATA box promoter region of maize Adh1 affects its organ-specific expression. AB - We have isolated two lineage-related Mutator (Mu3) transposon-induced Adh1 promoter mutants in maize: Adh1-3F1124 carries a duplicated TATA box and its revertant, Adh1-3F1124r17, bears a deleted TATA box. Both alterations lead to unique patterns of organ-specific ADH1 enzyme expression. Enzyme activity in Adh1 3F1124 sporophytic organs (scutellum and roots) is greatly reduced, while activity levels remain normal in the male gametophyte (pollen). Conversely, enzyme activity in Adh1-3F1124r17 roots and scutellum is partially restored, but is concomitantly reduced in pollen. Transcript analysis suggests (i) that the TATA box region of the Adh1 gene influences post-transcriptional processes in the male gametophyte but not in roots and (ii) that organ-specific transcription signals in the promoter are distinct from the previously identified anaerobic environment-specific cis-acting transcription signals. Different organs appear to provide surrogate TATA function in different ways, leading to organ-specific differences in the length of the Adh1 message 5' leader. PMID- 1740104 TI - A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus. AB - Familial neurohypophyseal diabetes insipidus in humans is a rare disease transmitted as an autosomal dominant trait. Affected individuals have very low or undetectable levels of circulating vasopressin and suffer from polydipsia and polyuria. An obvious candidate gene for the disease is the vasopressin neurophysin (AVP-NP) precursor gene on human chromosome 20. The 2 kb gene with three exons encodes a composite precursor protein consisting of the neuropeptide vasopressin and two associated proteins, neurophysin and a glycopeptide. Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members. Comparison of the nucleotide sequences shows a G----T transversion within the neurophysin-encoding exon B. This missense mutation converts a highly conserved glycine (Gly17 of neurophysin) to a valine residue. RFLP analysis of six related family members indicates cosegregation of the mutant allele with the DI phenotype. The mutation is not present in 96 chromosomes of an unrelated control group. These data suggest that a single amino acid exchange within a highly conserved domain of the human vasopressin-associated neurophysin is the primary cause of one form of ADNDI. PMID- 1740105 TI - The characterization of the promoter of the gene encoding the p50 subunit of NF kappa B indicates that it participates in its own regulation. AB - In order to characterize the regulation of the gene encoding the p50 subunit of the transcription factor NF-kappa B, we have isolated a human genomic clone, and sequenced the promoter of this gene. By in situ hybridization we have mapped the gene encoding the p50 subunit of NF-kappa B to the 4q23-4q25 region of the human genome and the H1-H3 region of the murine chromosome 3. The p50 promoter lacks TATA and CAAT elements, but contains NF-kappa B, AP-1 and HIP-1 binding sequence. The kappa B motif binds NF-kappa B, KBF1, and heterodimers of p50 and c-rel, suggesting that the gene is regulated by members of this family. Co-transfection experiments demonstrate that the p50 promoter can be activated by either of the two subunits of NF-kappa B (p50 and p65), and more strongly by the combination of both. The promoter of p50 can be activated by phorbol esters and tumor necrosis factor alpha but not by forskolin and these responses are mediated through the NF kappa B binding sequence. The involvement of NF-kappa B in the regulation of the p50 gene is also supported by the inhibition of the PMA activation of the promoter by an NF-kappa B transdominant negative mutant, as well as the product of the v-rel oncogene. PMID- 1740106 TI - A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. AB - The NF-kappa B subunits, p50 and p65, have extensive sequence homology with the c rel proto-oncogene and the Drosophila morphogen dorsal. It has recently been shown that in vitro translated c-Rel can bind to DNA and form a complex with p50. However, the conditions for DNA binding of c-Rel in vivo and its DNA sequence specificity have not been established. Here we report the identification a novel heterodimeric complex that binds to a kappa B-like, phorbol ester (TPA) responsive DNA sequence, 5'-GGGAAAGTAC-3', in the 5' flanking region of the human urokinase (uPA) gene. This sequence was shown to bind two protein complexes, LC and UC. LC was indistinguishable from NF-kappa B as it reacted with antibodies recognizing the p50 subunit of NF-kappa B, and was shown by UV crosslinking to contain the p50 and p65 subunits of NF-kappa B. UC, on the other hand, strongly reacted with anti-v-Rel, but not with the anti-p50 antibodies, and was shown by crosslinking to contain 75 kDa and 85 kDa protein-DNA adducts. The 75 kDa and the 85 kDa adducts could be immunoprecipitated only by anti-p65 and anti-c-Rel antibodies, respectively, showing that c-Rel formed a heterodimer with p65. Both protein complexes were present in inactive forms in HeLa cell cytosol, and their nuclear translocation was induced by TPA. DNA binding of UC and LC could, furthermore, be inhibited by I kappa B-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740107 TI - Biochemical and genetic analysis of operator contacts made by residues within the beta-sheet DNA binding motif of Mnt repressor. AB - Residues 2, 6, 8 and 10 of Mnt repressor are the major determinants of operator DNA binding and recognition. Here, we investigate the interaction of wild-type Mnt and mutants bearing the Arg2----Lys, His6----Ala, Asn8----Ala and Arg10--- Lys mutations with operator DNA modified by methylation or by symmetric base substitutions. The wild-type pattern of methylation interference is altered in specific ways for each of the mutant proteins. In addition, some of the mutant proteins show a 'loss of contact' phenotype with specific mutant operators. Taken together, these and previous results predict the following contacts between side chains in the Mnt tetramer and operator DNA: Arg2 recognizes the guanines at operator positions 10 and 12; His6 contacts the guanines at operator positions 5 and 17; Asn8 contacts operator positions 4, 7, 15 and 18; Arg10 contacts the guanines at operator positions 8 and 14. The proposed contacts can be accommodated in a structural model in which the anti-parallel beta-sheet motifs of Mnt dimers lie in the major grooves of each operator half-site, centered over pseudo-symmetry axes that are 5.5 bp from the central dyad axis of the operator. PMID- 1740108 TI - Recombination of constant and variable modules alters DNA sequence recognition by type IC restriction-modification enzymes. AB - EcoR124 and EcoDXXI are allelic type I restriction-modification (R-M) systems whose specificity genes consist of common structural elements: two variable regions are separated by a constant, homologous region containing a number of repetitive sequence elements. In vitro recombination of variable and constant elements has led to fully active, hybrid R-M systems exhibiting new and predictable target site specificities. Methylation of synthetic DNA sequences with purified, hybrid modification methylases was used to confirm the proposed recognition sequences. The results clearly demonstrate the correlation between protein domains and target site specificity. Our data suggest that a bacterial population may switch the recognition sequences of its type I R-M system by single recombination events and thus is able to maintain a prokaryotic analogue of the immune system of variable specificity. PMID- 1740109 TI - Characterization of a zinc finger DNA-binding protein expressed specifically in Petunia petals and seedlings. AB - In Petunia, the expression of the 5-enolpyruvylshikimate-3-phosphate synthase gene (EPSPS) is tissue-specific and developmentally regulated. Nuclear extracts from Petunia petal contain a factor that interacts with the 5' upstream region of EPSPS. DNase I footprinting experiments revealed four strong binding sites (EP1 EP4) and several weaker sites that appear to bind the same factor. We have isolated a cDNA clone (EPF1) encoding a DNA-binding protein that has similar binding activity to that of the nuclear factor. The deduced amino acid sequence shows that the encoded protein, EPF1, contains two repeats of a Cys2/His2 zinc finger motif. EPF1 and the factor detected in nuclear extracts appear to differ in their molecular weight and Zn2+ requirements. Nevertheless, Northern blot analyses showed that the expression pattern of EPF1 is remarkably similar to that of EPSPS. In addition, as determined by translational fusion of the EPF1 upstream region to the beta-glucuronidase reporter gene, the cell specific expression pattern of EPF1 in flower and seedling is nearly identical to that of EPSPS. Taken together with the results of cis-element analyses, these observations suggest that EPF1 may be one of the factors involved in the activation of EPSPS. PMID- 1740110 TI - Targeted alterations of the Caenorhabditis elegans genome by transgene instructed DNA double strand break repair following Tc1 excision. AB - Excision of a Tc1 transposon of Caenorhabditis elegans is thought to leave a DNA double strand break. We report here that sequence polymorphisms in a transgenic DNA template are copied into the corresponding chromosomal gene upon excision of Tc1 from the chromosome. This shows that the double strand DNA break resulting from Tc1 excision is repaired with the extrachromosomal DNA as template and that sequences flanking the break can be replaced by sequences from the transgene. Transgene instructed break repair provides a method for the targeted introduction of precise alterations into the Caenorhabditis elegans genome. PMID- 1740111 TI - Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm. AB - In Xenopus, growth factors of the TGF-beta, FGF and Wnt oncogene families have been proposed to play a role in generating embryonic pattern. In this paper we examine potential interactions between the bFGF and Xwnt-8 signaling pathways in the induction and dorsal-ventral patterning of mesoderm. Injection of Xwnt-8 mRNA into 2-cell Xenopus embryos does not induce mesoderm formation in animal cap ectoderm isolated from these embryos at the blastula stage, but alters the response of this tissue to mesoderm induction by bFGF. While animal cap explants isolated from non-injected embryos differentiate to form ventral types of mesoderm and muscle in response to bFGF, explants from Xwnt-8 injected embryos form dorsal mesodermal and neural tissues in response to the same concentration of bFGF, even if the ectoderm is isolated from the prospective ventral sides of embryos or from UV-ventralized animals. Our results support a model whereby dorso ventral mesodermal patterning can be attained by a single mesoderm inducing agent, possibly bFGF, which is uniformly distributed across the prospective dorsal-ventral axis, and which acts in concert with a dorsally localized signal, possibly a Wnt protein, which either alters the response of ectoderm to induction or modifies the character of mesoderm after its induction. PMID- 1740112 TI - Roles of U4 and U6 snRNAs in the assembly of splicing complexes. AB - A series of U4 and U6 snRNA mutants was analysed in Xenopus oocytes to determine whether they block splicing complex assembly or splicing itself. All the U4 and U6 mutants found to be inactive in splicing complementation resulted in defects in assembly of either U4/U6 snRNP or of splicing complexes. No mutants were found to separate the entry of U5 and U6 snRNAs into splicing complexes and neither of these RNAs was able to associate with the pre-mRNA in the absence of U4. In the absence of U6 snRNA, however, U4 entered a complex containing pre-mRNA as well as the U1 and U2 snRNAs. U6 nucleotides whose mutation resulted in specific blockage of the second step of splicing in Saccharomyces cerevisiae are shown not to be essential for splicing in the oocyte assay. The results are discussed in terms of the roles of U4 and U6 in the assembly and catalytic steps of the splicing process. PMID- 1740113 TI - Reconstituted mammalian U4/U6 snRNP complements splicing: a mutational analysis. AB - We have developed an in vitro complementation assay to analyse the functions of U6 small nuclear RNA (snRNA) in splicing and in the assembly of small nuclear ribonucleoproteins (snRNPs) and spliceosomes. U6-specific, biotinylated 2'-OMe RNA oligonucleotides were used to deplete nuclear extract of the U4/U6 snRNP and to affinity purify functional U4 snRNP. The addition of affinity purified U4 snRNP together with U6 RNA efficiently restored splicing activity, spliceosome assembly and U4/U5/U6 multi-snRNP formation in the U4/U6-depleted extract. Through a mutational analysis we have obtained evidence for multiple sequence elements of U6 RNA functioning during U4/U5/U6 multi-snRNP formation, spliceosome assembly and splicing. Surprisingly, the entire 5' terminal domain of U6 RNA is dispensable for splicing function. In contrast, two regions in the central and 3' terminal domain are required for the assembly of a functional U4/U5/U6 multi snRNP. Another sequence in the 3' terminal domain plays an essential role in spliceosome assembly; a model is strongly supported whereby base pairing between this sequence and U2 RNA plays an important role during assembly of a functional spliceosome. PMID- 1740114 TI - The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. AB - Influenza virus neuraminidase catalyses the cleavage of terminal sialic acid, the viral receptor, from carbohydrate chains on glycoproteins and glycolipids. We present the crystal structure of the enzymatically active head of influenza B virus neuraminidase from the strain B/Beijing/1/87. The native structure has been refined to a crystallographic R-factor of 14.8% at 2.2 A resolution and its complex with sialic acid refined at 2.8 A resolution. The overall fold of the molecule is very similar to the already known structure of neuraminidase from influenza A virus, with which there is amino acid sequence homology of approximately 30%. Two calcium binding sites have been identified. One of them, previously undescribed, is located between the active site and a large surface antigenic loop. The calcium ion is octahedrally co-ordinated by five oxygen atoms from the protein and one water molecule. Sequence comparisons suggest that this calcium site should occur in all influenza A and B virus neuraminidases. Soaking of sialic acid into the crystals has enabled the mode of binding of the reaction product in the putative active site pocket to be revealed. All the large side groups of the sialic acid are equatorial and are specifically recognized by nine fully conserved active site residues. These in turn are stabilized by a second shell of 10 highly conserved residues principally by an extensive network of hydrogen bonds. PMID- 1740115 TI - Identification and characterization of an Escherichia coli gene required for the formation of correctly folded alkaline phosphatase, a periplasmic enzyme. AB - Tn5 insertion mutations of Escherichia coli were isolated that impaired the formation of correctly folded alkaline phosphatase (PhoA) in the periplasm. The PhoA polypeptide synthesized in the mutants was translocated across the cytoplasmic membrane but not released into the periplasmic space. It was susceptible to degradation by proteases in vivo and in vitro. The wild-type counterpart of this gene (named ppfA) has been sequenced and shown to encode a periplasmic protein with a pair of potentially redox-active cysteine residues. PhoA synthesized in the mutants indeed lacked disulfide bridges. These results indicate that the folding of PhoA in vivo is not spontaneous but catalyzed at least at the disulfide bond formation step. PMID- 1740116 TI - Interconversion of three differentially modified and assembled forms of BiP. AB - The immunoglobulin heavy chain binding protein BiP/GRP78 is post-translationally modified by phosphorylation and ADP ribosylation. In cells induced to synthesize higher levels of BiP, either due to the accumulation of nontransported proteins or to glucose starvation, both BiP phosphorylation and ADP ribosylation are reduced. BiP bound to other proteins is unmodified, suggesting that both phosphorylation and ADP ribosylation are restricted to the unbound BiP pool. In the present study, both modifications were further characterized in terms of their stability, the pool of BiP that harbored these modifications, and the relationship between the modified and unmodified forms of BiP. While levels of BiP synthesis vary according to the physiological state of a cell, we found that both induced and uninduced cells contain similar amounts of free BiP. However, free BiP in uninduced cells was found primarily in an aggregated state, whereas in cells that accumulate nontransported proteins, it was predominantly monomeric. Both phosphorylation and ADP ribosylation were restricted to the aggregated form of free BiP. These post-translational modifications occurred upon release of BiP from associated proteins, and could be reversed upon induction of BiP synthesis. Therefore, BiP exists either (1) complexed to other proteins, (2) as a free unmodified monomer, or (3) as free modified aggregates. Our data suggest that BiP can be interconverted from one state to another, and that the various forms are functionally distinct. PMID- 1740117 TI - Involvement of the chaperonin dnaK in the rapid degradation of a mutant protein in Escherichia coli. AB - The ability of Escherichia coli rapidly to degrade abnormal proteins is inhibited by mutations affecting any of several heat shock proteins (hsps). We therefore tested whether a short-lived mutant protein might become associated with hsps as part of its degradation. At 30 degrees C, the non-secreted mutant form of alkaline phosphatase, phoA61, is relatively stable, and very little phoA61 is found associated with the hsp dnaK. However, raising the temperature to 37 degrees C or 41 degrees C stimulated the degradation of this protein, and up to 30% of cellular phoA61 became associated with dnaK, as shown by immunoprecipitation and Western blot analysis. Also found in complexes with phoA61 were the hsps, protease La and grpE (but no groEL, or groES). The rapid degradation of phoA61 at 37 degrees C and 41 degrees C is in part by protease La, since it decreased by 50% in lon mutants. This process also requires dnaK, since deletion of this gene prevented phoA61 degradation almost completely (unless a wild-type dnaK gene was introduced). In contrast, the missense mutation, dnaK756, enhanced phoA61 degradation. The dnaK756 protein also was associated with phoA61, but this complex, unlike that containing wild-type dnaK could not be dissociated by ATP addition. Furthermore, in a grpE mutant, the degradation of phoA61 and the amount associated with dnaK increased, while in a dnaJ mutant, phoA61 degradation and its association with dnaK decreased. Thus, complex formation with dnaK appears essential for phoA61 degradation by protease La and some other cell proteases, and a failure of the dnaK to dissociate normally may accelerate proteolytic attack.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740118 TI - Insertion and assembly of the precursor of subunit II into the photosystem I complex may precede its processing. AB - The biogenesis and assembly of subunit II of photosystem I (PSI) (psaD gene product) were studied and characterized. The precursor and the mature form were produced in vitro and incubated with intact plastids or isolated thylakoids. Following import of the precursor into isolated plastids, mostly the mature form of subunit II was found in the thylakoids. However, when the processing activity was inhibited only the precursor form was present in the membranes. The precursor was processed by a stromal peptidase and processing could occur before or after insertion of the precursor into the thylakoids. Following insertion into isolated thylakoids, both the precursor and the mature form of subunit II were confined to the PSI complex. Insertion of the mature form of subunit II was much less efficient than that of the precursor. Kinetic studies showed that the precursor was inserted into the membrane. Only at a later stage, the mature form began to accumulate. These results suggest that in vivo the precursor of subunit II is inserted and embedded in the thylakoids, as part of the PSI complex. Only later, it is processed to the mature form through the action of a stromal peptidase. PMID- 1740119 TI - Casein kinase II phosphorylation increases the rate of serum response factor binding site exchange. AB - Recombinant baculoviruses were used to express wild-type serum response factor (SRF) and a mutant, SRF.CKIIA, which lacks all four serine residues in the major casein kinase II (CKII) site at residues 77-90. Purified recombinant SRF binds DNA with an affinity and specificity indistinguishable from that of HeLa cell SRF, and activates transcription in vitro. Comparative phosphopeptide analysis of the wild-type and mutant proteins demonstrated that the wild-type protein is phosphorylated at the major CKII site in insect cells. Dephosphorylation of recombinant SRF does not affect its affinity for the c-fos SRE, and results in only a 3-fold reduction in binding to the synthetic site ACT.L. However, dephosphorylation does cause a large decrease in the rates of association with and dissociation from either site. These effects are due solely to phosphorylation at the major CKII site: the binding properties of the SRF.CKIIA mutant are identical to those of dephosphorylated wild-type SRF, and CKII phosphorylation in vitro converts dephosphorylated wild-type SRF from a slow binding to a fast-binding form without significantly changing binding affinity. CKII phosphorylation thus acts to potentiate SRF-DNA exchange rates rather than alter equilibrium binding affinity. PMID- 1740120 TI - cis-diol dehydrogenases encoded by the TOL pWW0 plasmid xylL gene and the Acinetobacter calcoaceticus chromosomal benD gene are members of the short-chain alcohol dehydrogenase superfamily. AB - In the aerobic degradation of benzoate by bacteria, benzoate is first dihydroxylated by a ring-hydroxylating dioxygenase to form a cis-diol (1,2 dihydroxycyclohexa-3,4-diene carboxylate) which is subsequently transformed to a catechol by an NAD(+)-dependent cis-diol dehydrogenase. The structural gene for this dehydrogenase, encoded on TOL plasmid pWW0 of Pseudomonas putida (xylL) and that encoded on the chromosome of Acinetobacter calcoaceticus (benD), were sequenced. They encode polypeptides of about 28 kDa in size. These proteins are similar to each other, exhibiting 58% sequence identity. They are also similar to other proteins of at least 20 different functions, which are members of the short chain alcohol dehydrogenase family. The alignment of these proteins suggest two amino acids, lysine and tyrosine, as catalytically important residues. PMID- 1740121 TI - Expression of the Saccharomyces cerevisiae Kex2p endoprotease in inset cells. Evidence for a carboxy-terminal autoprocessing event. AB - The pheromone-processing Kex2p endoprotease of Saccharomyces cerevisiae has been difficult to characterize due to its low level of expression in yeast cells. To overcome this problem, we have overexpressed Kex2p using the baculovirus/insect cell expression system. Spodoptera frugiperda Sf9 insect cells infected with a recombinant baculovirus, containing the complete KEX2 gene which encodes the Kex2p protease (814 amino acids), accumulate an 120-kDa functional form of the enzyme. The inhibition profile of the insect-cell-derived endoprotease is similar to that of the yeast enzyme. The recombinant infected insect cells also secrete into the medium about half of the total Kex2p activity produced. Deleting the carboxyl-terminal tail and the transmembrane domain of Kex2p (Kex2 delta p, 666 amino acids) does not measurably interfere with the enzyme characteristics and results in the secretion of up to 90% of the total enzyme activity. The truncated form, Kex2 delta p, of the endoprotease accumulates in the cell supernatant to 6.7 x 10(5) U/l. The molecular mass of the secreted forms for both the wild-type Kex2p and Kex2 delta p is the same (70 kDa) and is 50-kDa lower than the intracellular form. This result implicates a processing event which gives rise to shorter extracellular forms of both the wild-type Kex2p and Kex2 delta p and which trims their carboxy termini upsteam of amino acid 666. This processing event requires the integrity of the Ser385 of the Kex2p active site. PMID- 1740122 TI - Interaction of Prodan with tubulin. A fluorescence spectroscopic study. AB - The compound 6-propionyl-2-(N,N-dimethyl)-aminonaphthalene (Prodan), an efficient fluorescent probe for proteins, is shown to bind to tubulin. Detailed experiments on fluorescence enhancement, anisotropy and energy transfer were carried out to unravel the nature of Prodan-tubulin interaction and the Prodan-binding site on tubulin. It was found that Prodan binds to tubulin at a rigid site, with a stoichiometry of 1:1 and a dissociation constant of 20 microM. Competition experiments using 1,8-[3H]anilinonaphthalenesulfonate ([3H]ANS) indicated that the three aminonaphthalenes, ANS, bis(1,8-anilinonaphthalenesulfonate) and Prodan probably bind to a common region on the tubulin molecule. PMID- 1740123 TI - Structure of the Clostridium thermocellum gene licB and the encoded beta-1,3-1,4 glucanase. A catalytic region homologous to Bacillus lichenases joined to the reiterated domain of clostridial cellulases. AB - The nucleotide sequence of the Clostridium thermocellum gene licB, coding for a thermoactive beta-1,3-1,4-glucanase, has been determined. The gene is located downstream, but in opposite orientation to the beta-glucosidase gene bglA. A coding region of 1002 bp is flanked by canonical promoter and transcription terminator sequences. The primary translation product of the licB gene has a predicted molecular mass of 37,896 Da. The protein sequence can be divided into several discrete segments: an N-terminal signal peptide, a catalytic region, a segment rich in Pro and Thr residues and a C-terminal reiterated domain. The catalytic region shows close similarity to lichenases of bacilli (52-58% identity) and Fibrobacter succinogenes (35% identity), but is unrelated to barley beta-1,3-1,4-glucanases. It consists of two domains, which in the case of the F. succinogenes lichenase are arranged in reversed order to that of C. thermocellum and Bacillus lichenases. The C-terminal reiterated domain of C. thermocellum lichenase is homologous to the duplicated non-catalytic domain of endo-beta-1,4 glucanases and xylanase Z from the same organism. This domain is considered a characteristic feature of clostridial cellulases organized as multienzyme complex (cellulosome). The beta-1,3-1,4-glucanase encoded by the licB gene might therefore be an additional enzyme component of the C. thermocellum cellulosome. PMID- 1740124 TI - Sequence-specific NMR assignments of the trp repressor from Escherichia coli using three-dimensional 15N/1H heteronuclear techniques. AB - Sequence-specific 15N and 1H assignments for the trp holorepressor from Escherichia coli are reported. The trp repressor consists of two identical 107 residue subunits which are highly helical in the crystal state [Schevitz, R., Otwinowski, Z., Joachimiak, A., Lawson, C. L. & Sigler, P. B. (1985) Nature 317, 782-786]. The high helical content and the relatively large size of the protein (Mr = 25,000) make it difficult to assign even the main-chain resonances by conventional homonuclear two-dimensional NMR methods. However, we have now assigned the main-chain resonances of 94% of the residues by using three dimensional 15N/1H heteronuclear experiments on a sample of protein uniformly labelled with 15N. The additional resolution obtained by spreading out the signals into three dimensions proved indispensable in making these assignments. In particular, we have been able to resolve signals from residues in the N terminal region of the A helix for the first time in solution. The observed NOE results confirm that the repressor is highly helical in solution, and contains no extended chain conformations. PMID- 1740125 TI - Isolation and structural determination of three peptides from the insect Locusta migratoria. Identification of a deoxyhexose-linked peptide. AB - We have isolated three novel peptides from the aqueous extract of the pars intercerebralis of male and female adults of the insect Locusta migratoria. After extensive HPLC purification, the peptides were characterised by automated Edman degradation and electrospray mass spectrometry: one is a 35-residue peptide (3752.3 +/- 1.1 Da) containing six cysteines involved in three intramolecular disulfide bridges, the second is a 36-residue peptide (3919.2 +/- 0.9 Da), also cross-linked by three intramolecular disulfide bridges. This second peptide is post-translationally modified by a single fucose moiety, which was identified by gas chromatography coupled to mass spectrometry. These two peptides show a strong sequence similarity. Additionally, they were also found in larger amounts in the fat body of Locusta; this finding raises the question of their exact site of synthesis. The third peptide (5776.3 +/- 0.9 Da), a 54-residue peptide cross linked by six intramolecular disulfide bridges, is structurally related to the two other peptides, but to a lesser extent. Mass spectrometry has shown that all the cysteines within these three peptides are involved in intramolecular disulfide bridges; however, the location of these bridges is not yet established and is currently being investigated. A computer search of sequence data banks did not reveal any significant similarity of these three peptides with other known proteins. PMID- 1740126 TI - Studies on the variants of the protein toxins ricin and abrin. AB - This study elucidates some structural and biological features of galactose binding variants of the cytotoxic proteins ricin and abrin. An isolation procedure is reported for ricin variants from Ricinus communis seeds by using lactamyl-Sepharose affinity matrix, similar to that reported previously for variants of abrin from Abrus precatorius seeds [Hegde, R., Maiti, T. K. & Podder, S. K. (1991) Anal. Biochem. 194, 101-109]. Ricin variants, subfractionated on carboxymethyl-Sepharose CL-6B ion-exchange chromatography, were characterized further by SDS/PAGE, IEF and a binding assay. Based on the immunological cross reactivity of antibody raised against a single variant of each of ricin and abrin, it was established that all the variants of the corresponding type are immunologically indistinguishable. Analysis of protein titration curves on an immobilized pH gradient indicated that variants of abrin I differ from other abrin variants, mainly in their acidic groups and that variance in ricin is a cause of charge substitution. Detection of subunit variants of proteins by two dimensional gel electrophoresis showed that there are twice as many subunit variants as there are variants of holoproteins, suggesting that each variant has a set of subunit variants, which, although homologous, are not identical to the subunits of any other variant with respect to pI. Seeds obtained from polymorphic species of R. communis showed no difference in the profile of toxin variants, as analyzed by isoelectric focussing. Toxin variants obtained from red and white varieties of A. precatorius, however, showed some difference in the number of variants as well as in their relative intensities. Furthermore, variants analyzed from several single seeds of A. precatorius red type revealed a controlled distribution of lectin variants in three specific groups, indicating an involvement of at least three genes in the production of Abrus lectins. The complete absence or presence of variants in each group suggested a post translational differential proteolytic processing, a secondary event in the production of abrin variants. PMID- 1740127 TI - 31P-NMR assignment and conformational study of NADPH bound to Lactobacillus casei dihydrofolate reductase based on two-dimensional 1H-31P-heteronuclear and 1H detected 1H-31P-shift-correlation experiments. AB - For any detailed NMR conformational study of a protein-ligand complex it is essential to have specific resonance assignments. We have now assigned the pyrophosphate 31P resonances in spectra of NADPH bound to Lactobacillus casei dihydrofolate reductase (DHFR) by using a combination of 1H-31P-heteronuclear shift-correlation (HETCOR), 1H-31P-heteronuclear multiple-quantum-coherence correlation spectroscopy (HMQC-COSY), 1H-1H COSY, homonuclear Hartmann-Hahn (HOHAHA) and NOE spectroscopy (NOESY) experiments. The nicotinamide pyrophosphate phosphorus, P(n), has been unequivocally assigned to a signal (-14.07 ppm) which shows a large 3JP-O-C-H coupling constant. Such a coupling constant when combined with the appropriate Karplus relationship provides conformational information about the P-O-C-H torsion angle. The torsion angle changes by 65 degrees +/- 10 degrees for the binary complex compared with the value in free NADPH. The observed coupling constants for the binary (DHFR--NADPH) and ternary (DHFR--NADPH -methotrexate) complexes (12.3 and 10.5 +/- 0.6 Hz, respectively) indicate that the pyrophosphate group has a similar conformation in the two complexes. PMID- 1740128 TI - Effects of ions on the intrinsic activities of c-H-ras protein p21. A comparison with elongation factor Tu. AB - The influence of the ionic environment on the intrinsic GTPase activity and the guanine-nucleotide interaction of Ha-ras protein p21 were studied in various experimental conditions and compared with the behaviour of elongation factor (EF) Tu. To this purpose, nucleotide-free p21 was prepared, which is much more stable than by any other reported method. Specific differences between p21 and EF-Tu were found in the action of divalent anions which strongly enhance the dissociation rate of p21.GDP without affecting that of EF-Tu. Unlike EF-Tu, the GTPase activity of p21 is only slightly dependent on the presence and concentration of monovalent cations. The concentrations of Mg2+ influencing the dissociation rate of the p21.GDP complex are much higher than for the intrinsic GTPase activity, an effect also observed for EF-Tu. These results point to two distinct roles of Mg2+: as a conformational regulator of the interaction with the substrate and as a key element for the hydrolysis of GTP. The GTPase activity of p21 is not affected by changes in pH over the range 6-9.2, different from that of EF-Tu. However, stabilization by kirromycin confers a pH independence to the GTPase of EF-Tu in the pH range 6.5-10, suggesting that the bell-shaped behaviour of this activity in the absence of the antibiotic is due to denaturation. This implies similar properties in the catalytic mechanism of these two guanine nucleotide-binding proteins. PMID- 1740129 TI - Action pattern of xylo-oligosaccharide hydrolysis by Schizophyllum commune xylanase A. AB - The endo-1,4-beta-xylanase of the basidiomycete Schizophyllum commune, designated xylanase A, was studied to determine its action pattern, rates of reaction and bond-cleavage frequencies on xylo-oligomer and xylo-alditol substrates ranging in degree of polymerization (Dp) from xylotriose (X3) to xyloheptaose (X7). An HPLC method using a Dionex HPLC and Carbopac PA1 ion-exchange column with pulsed amperometric detection was developed to quantify both substrate loss and increase of products. Xylanase A had no detectable activity on xylobiose (X2) and low activity on xylotriose and xylotetraose (X4) but cleaved X5-X7 rapidly with X2 and X3 as major products. Initial rate data from hydrolyses of individual oligomers at 25 degrees C and pH 5.81 indicated that the Michaelis constant (Km) decreased with increasing chain length (n) of oligomer. Turnover number (kcat) increased with chain length up to n = 7 suggesting that the specificity region of xylanase A spans about seven xylose units. Bond-cleavage frequencies obtained from xylanase A hydrolysis of xylo-alditols indicated a strong preference for internal linkages of the xylose chain. The action pattern of xylanase A on reduced substrates suggests that the catalytic site is located assymetrically within the binding cleft of the enzyme. PMID- 1740130 TI - Cytoplasmic high-level expression of a soluble, enzymatically active form of the Escherichia coli penicillin-binding protein 5 and purification by dye chromatography. AB - High-level expression of a soluble form of penicillin-binding protein 5 (PBP5), called PBP5s, and translocation across the cytoplasmic membrane results in lysis of Escherichia coli cells. The detrimental effect of increased amounts of this D,D-carboxypeptidase on the stability of murein polymer can be avoided by accumulation of the overexpressed protein in the cytoplasm. The signal peptide of the structural gene dacAs, coding for PBP5s was deleted by creating a BamHI site at the site of processing and the truncated gene dacAsc was cloned under the control of the lambda PR promoter. Temperature induction resulted in a 200-fold overproduction of the mature PBP5s in the cytosol (PBP5sc) which is no longer harmful to the cells. PBP5sc could quantitatively be recovered in the soluble fraction after disrupting the cells. The protein retained full enzymatic activity as measured by the release of D-alanine from bisacetyl-L-Lys-D-Ala-D-Ala and formation of [14C]penicillin-protein complex at a 1:1 stoichiometry. A one-step purification procedure using the immobilized dye Procion rubine MX-B resulted in homogeneous preparations of both wild-type and mutated forms of PBP5sc. PMID- 1740131 TI - Use of influenza C virus for detection of 9-O-acetylated sialic acids on immobilized glycoconjugates by esterase activity. AB - An overlay and a solid-phase assay are presented which allow the specific detection of 9-O-acetylated sialic acids on sialoglycoconjugates immobilized on microtiter plates, nitrocellulose or separated on thin-layer chromatograms. The assay takes advantage of two different biological properties of influenza C virus, its high-affinity binding to 9-O-acetylated sialic acids and its sialate 9 O-acetylesterase that is used for detection of bound virus with fluorogenic or chromogenic substrates. Though simple and rapid, the assay is highly sensitive with a detection limit of 65 fmol 9-O-acetylated sialic acid in 9-O-acetylated ganglioside GD1a. Influenza C virus is able to bind to a wide spectrum of sialoglycoconjugates like mucins, serum glycoproteins or gangliosides containing naturally or synthetically O-acetylated sialic acids. 9-O-Acetyl-N glycoloylneuraminic acid can also function as a high-affinity receptor determinant for influenza C virus. While the acetyl ester at the 9 position is essential for virus binding in all cases, a 4-O-acetyl group is not recognized. In addition to alpha(2.3) or alpha(2.6) bonds, 9-O-acetyl-N-acetylneuraminic acid in alpha(2.8) linkage to N-acetylneuraminic acid is also functionally active. PMID- 1740132 TI - Cross-species comparison of the sequence of the leukaemia inhibitory factor gene and its protein. AB - Leukaemia inhibitory factor (LIF) is a pleiotropic growth factor active in diverse cell systems in both the adult and the embryo. The LIF gene from a number of mammalian species is highly conserved. The ovine and porcine LIF genes were cloned, sequenced and compared to the previously published murine and human LIF gene sequences. While the coding regions of the LIF gene are highly conserved, the non-coding regions are largely non-conserved. In a region of approximately 340 bp, the 5' end of the translational initiation codon is highly conserved (84%). This region includes four conserved TATA boxes, two transcriptional start sites identified in the murine gene and the minimal region required to function as the LIF promoter. A sequence in the murine gene adjacent to this highly conserved region which appears to contain a negative control element is, however, poorly conserved between the four species compared, except for a sequence of 16 conserved nucleotides. Within the largely non-conserved first intron, there is a block of approximately 150 nucleotides which is highly conserved between all four species (approximately 72%). However, a sequence in intron 1 of the murine LIF gene which corresponds to an alternative exon of a putative variant LIF transcript is very poorly conserved between species, with only relics of this exon evident in the other three species. A comparison of the five LIF protein sequences available (murine, rat, human, ovine and porcine) revealed that the protein displays a high degree of similarity, ranging from 74% between mouse and sheep to 92% between rat and mouse. Several large blocks of absolutely conserved amino acid sequence were identified. The ovine LIF gene was modified to allow production of recombinant ovine LIF in yeast cells, which was shown to be biologically active on murine cells. PMID- 1740133 TI - Structure of the capsular polysaccharide of Actinobacillus pleuropneumoniae serotype 5b. AB - The capsular polysaccharide of Actinobacillus pleuropneumoniae serotype 5b (strain L20) was found to be a high molecular mass polymer composed of 2 acetamido-2-deoxy-D-glucose, D-glucose, and 3-deoxy-D-manno-octulosonic acid (KDO). Methylation analysis, partial hydrolysis and a combination of homonuclear and 1H-detected heteronuclear shift-correlated nuclear magnetic resonance experiments showed the polysaccharide to be a branched polymer of a trisaccharide repeating unit, having the structure: [formula; see text] PMID- 1740134 TI - Membrane protein acylation. Preference for exogenous myristic acid or endogenous saturated chains in Acholeplasma laidlawii. AB - Mycoplasmas are small bacteria without a cell wall, often found as surface parasites on eukaryotic cells. Of the more than 200 membrane proteins from Acholeplasma laidlawii resolved by two-dimensional PAGE, 23 were covalently modified with acyl chains. These acyl proteins had lower pI values than average and were all labelled by different exogenously supplied radioactive fatty acids attached by O-ester bonds. The fatty acids were selectively incorporated in the order myristic acid (14:0) greater than palmitic acid (16:0) greater than stearic acid (18:0) greater than oleic acid (18:1). However, endogenously synthesised saturated fatty acids, most of which were 16:0, were preferred over the supplied ones. A fraction of the exogenous 14:0 was elongated to 16:0. Absence of saturated fatty acids increased the incorporation of 18:1. The maximum extent of modification was one acyl chain for protein T2, on the exterior surface and two acyl chains for protein D12, spanning them membrane. Exogenously supplied fatty acids were incorporated into membrane lipids in proportion to their occurrence. However, the acylated proteins always contained 8-10 times more saturated chains than did the lipids. When exogenously supplied, all A. laidlawii polar membrane lipids could donate acyl chains to the acylated proteins but the neutral fraction (fatty acids and diacylglycerol) was most efficient. An incorporation into the acylated proteins of labelled cysteine, but not glucose or glycerol, was observed. Acylated proteins with different chains interacted similarly with a Triton X-114 detergent phase, and no full-size proteins (or acylated fragments) were released from cells by proteolytic enzymes. The results indicate an anchoring with peptide segments in addition to the acyl chains. Both 14:0 and 16:0 were attached at one end of both T2 and D12, but the N-terminal methionine of T2 was not acylated. The extent of modification and preference for saturated chains in the A. laidlawii membrane acylated proteins is more similar to eukaryotic than to eubacterial proteins. PMID- 1740135 TI - Characterization of a recombinant bifunctional enzyme, galactose dehydrogenase/bacterial luciferase, displaying an improved bioluminescence in a three-enzyme system. AB - The two structural genes encoding galactose dehydrogenase (Pseudomonas fluorescens) and the beta subunit of luciferase (Vibrio harveyi) were fused in frame in order to prepare and subsequently characterize an artificial bifunctional enzyme complex. This hybrid enzyme exhibited both galactose dehydrogenase activity and bioluminescence when expressed in Escherichia coli together with the alpha subunit of luciferase. The purified conjugate was used to study possible proximity effects in a sequential three-enzyme reaction with the bifunctional enzyme catalyzing the first and the last reaction. The intermediate enzyme, diaphorase, was added separately. The engineered enzyme system, comprising the galactose dehydrogenase/luciferase conjugate, could display a twofold higher bioluminescence in the overall enzyme reaction compared to a corresponding reference system with separate native enzymes. The increased bioluminescence obtained for the engineered enzyme system is proposed to be due to an improved organization of the enzyme in solution. PMID- 1740136 TI - Redox control of catalysis in ATP-citrate lysate from rat liver. AB - In thiol redox buffers at pH 8.0, rat liver ATP-citrate lyase is in equilibrium between an oxidised inactive form and a reduced active form. The reduced enzyme is inactivated by oxidised glutathione (GSSG) at a rate of 45 min-1.M-1 and the oxidised enzyme is activated by reduced glutathione (GSH) at a rate of 3.2 min 1.M-1. At redox equilibrium, the enzyme activity depends on the ratio [GSH]2/[GSSG]. The inactivation involves formation of a protein-protein disulphide rather than a protein-glutathione complex. This reaction has Keq = 78 +/- 7 mM for the oxidative reaction. Activity can therefore be controlled by the redox state of the cell, being more active in the fed state than in the oxidatively stressed state. This redox process is also important in the in vitro enzyme assay, where ATP-citrate lyase is in redox equilibrium with oxygen and either dithiothreitol or 2-mercaptoethanol. Reduction is a two-step process, requiring high concentrations of reductant for full activation (30 mM dithiothreitol or 200 mM 2-mercaptoethanol). The enzyme inhibitor, Medica-16 raises the redox equilibrium constant to greater than 400 mM. It binds more tightly to the oxidised form of the enzyme, with Ki less than 40 microM compared to 180 microM for the reduced form. PMID- 1740137 TI - Channelling can decrease pool size. AB - It is widely considered that a possible advantage of metabolite channelling, in which a product of an enzyme is transferred to the next enzyme in a metabolic pathway without being released to the 'bulk' solution, is that channelling can decrease the steady-state concentrations of 'pool' intermediates. This then spares the limited solvent capacity of the cell, and reduces the loss of pathway flux due to leakage or instability of the free intermediate. Recently, however, based on simulations of a particular model of a 'dynamic' channel, Cornish-Bowden ["Failure of channelling to maintain low concentrations of metabolic intermediates" (1991) Eur. J. Biochem. 195, 103-108] has argued that this is not in fact the case; his simulations indicated that the channel was rather ineffective at decreasing the concentration of the pool intermediate, and in some cases actually increased it. However, although his simulations were restricted to very specific thermodynamic and kinetic parameters, he generalised his conclusions, arguing that "channelling has no effect on the free concentration of a channelled intermediate in a pathway". By showing that, for a number of kinetic cases, the concentration of the pool intermediate did decrease substantially with increased channelling, we demonstrate here that the conclusion of Cornish-Bowden is not correct. In particular, if the reaction catalysed by the enzymes forming the channel has an equilibrium constant K higher than 1, and if the enzyme removing the product of the channel reaction is kinetically competent, channelling in the model system studied by Cornish-Bowden (1991) can decrease the steady-state concentration of the pool by a factor of 1000, independently of the mechanism of the terminal reaction and under conditions of essentially constant overall flux. If the channel is a 'static' channel, the decrease in the pool can be to arbitrarily low levels. This conclusion also holds for a system in which other reactions may consume the pool intermediate. Thus, channelling can maintain metabolite concentrations at low levels. PMID- 1740138 TI - Repair of transcriptionally active and inactive genes during S and G2 phases of the cell cycle. AB - To study the effect of ultraviolet irradiation on S and G2 phases of the cell cycle, BB88 mouse cells synchronized by a double thymidine block were exposed to ultraviolet light, and rates of DNA synthesis and mitotic indexes were determined at regular intervals. It was found that with increasing ultraviolet dose, semiconservative DNA synthesis decreased and the sharp mitotic wave observed in the unirradiated cells gradually degenerated. To study repair, semiconservative DNA replication was inhibited with hydroxyurea at different time intervals after releasing cells from the block and the DNA synthesized as a result of repair of the ultraviolet damage was labeled with 5'-bromodeoxyuridine (BrdU). The newly repaired DNA was separated from bulk DNA by immunoprecipitation with monoclonal anti-BrdU antibody, labeled with 32P and hybridized to nine different gene and oncogene probes dot-blotted in excess on nylon membranes to determine their abundance in the repaired DNA. The results showed that: (a) the most actively repaired segment was a 211-bp sequence adjacent to the promotor region of the beta-actin gene; (b) all transcriptionally active genes were repaired at similar and constant rates throughout S and G2 phases; (c) the nontranscribed genes were repaired at much lower rates in early S phase, but later in S phase and especially in G2 phase, their repair rates increased and approached those of the transcribed genes. PMID- 1740139 TI - Pharmacological and biochemical characterization of cholecystokinin/gastrin receptors in developing rat pancreas. Age-related expression of distinct receptor glycoforms. AB - Cholecystokinin/gastrin receptors in the pancreas of newborn (3-day-old) rats are of type A, as in control mature rats, revealed by pharmacological analysis of specific 125I-Bolton-Hunter-reagent-labelled [Thr34,Ahx37]cholecystokinin(31-39) (Ahx, aminohexanoic acid) binding. Also, by 1 day post-partum, pancreatic cholecystokinin receptors were shown to be coupled to guanine-nucleotide-binding regulatory (G) proteins. Scatchard analysis of 125I-Bolton-Hunter-reagent labelled [Thr34,Ahx37]cholecystokinin(31-39) binding to pancreatic membranes from rats at different times after birth showed a slight increase in the binding capacity of cholecystokinin receptors between days 3 and 14 and a sixfold increase in 21-day-old rats, with no change in receptor affinity during development. SDS/PAGE analysis of pancreatic membranes affinity labelled with the photoactivable ligand 125I-[2-(p-azidosalicylamido)-1,3'-dithiopropionate] labelled [Thr34,Ahx37]cholecystokinin-(31-39) identified cholecystokinin receptors of 100-135 kDa in 3-day-old rats, 96-130 kDa in 7-day-old rats, 90-125 kDa in 10-day-old rats and 85-100 kDa in 14-day-old and 21-day-old rats, as found in control adult rats. Endo-beta-N-acetylglucosaminidase F treatment yielded a core protein of 42 kDa in all developmental stages. These findings are consistent with an age-related postnatal expression of distinct glycoforms of pancreatic cholecystokinin receptors. Furthermore, it was observed that the period 2-3 weeks after birth, characterized by stabilization of the mass of the cholecystokinin receptor, precedes the dramatic increase in the receptor number. PMID- 1740140 TI - Role of the beta subunit of casein kinase-2 on the stability and specificity of the recombinant reconstituted holoenzyme. AB - Recombinant human alpha subunit from casein kinase-2 (CK-2) was subjected, either alone or in combination with recombinant human beta subunit, to high temperature, tryptic digestion and urea treatment. In all three cases, it was shown that the presence of the beta subunit could drastically reduce the loss of kinase activity, strongly suggesting a protective function for the beta subunit. Assaying different peptides for specificity toward the recombinant alpha subunit and the recombinant reconstituted enzyme, showed that the presence of the beta subunit could modify the specificity of the catalytic alpha subunit. Therefore, a dual function for the beta subunit is proposed which confers both specificity and stability to the catalytic alpha subunit within the CK-2 holoenzyme complex. The peptide DLEPDEELEDNPNQSDL, reproducing the highly acidic amino acid 55-71 segment of the human beta subunit, counteracts the stimulatory effect of the beta subunit on the alpha subunit activity and partially substitutes the beta subunit in conferring thermal stability to the alpha subunit. No such effect is induced by the peptide MSSSEEVSW, reproducing the N-terminal segment of the beta subunit including the autophosphorylation site. It is suggested that the acidic domain of the beta subunit, encompassing residues 55-71, plays a role in the interactions between the beta and alpha subunits. PMID- 1740142 TI - ADP-ribosylation of actins by arginine-specific ADP-ribosyltransferase purified from chicken heterophils. AB - We reported the purification and characterization of an arginine-specific ADP ribosyltransferase and acceptor protein p33 in granules of chicken peripheral polymorphonuclear leukocytes (heterophils) [Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K. & Shimoyama, M. (1991) J. Biochem. (Tokyo) 110, 388 394]. In the present study, we obtained evidence that chicken non-muscle beta/gamma-actin, skeletal muscle alpha-actin and smooth-muscle gamma-actin were ADP ribosylated by the heterophil ADP-ribosyltransferase. The stoichiometry of ADP-ribose incorporation into these actins was 1.2 mol, 1.0 mol and 2.0 mol ADP ribose/mol of beta/gamma-actin, alpha-actin and gamma-actin, respectively. The optimal pH for the ADP ribosylation was at pH 8.5, with the respective actin. Km values for NAD were calculated to be 30 microM with beta/gamma-actin, 35 microM with alpha-actin and 20 microM with gamma-actin. The Km values for the actin isoforms were 15 microM for beta/gamma-actin, 2.5 microM for alpha-actin and 10 microM for gamma-actin. ADP ribosylation of actin inhibited its capacity to polymerize, as determined by the increase in fluorescence intensity with N-(1 pyrenyl)iodoacetamide-labelled actin. Filamentous actin (F-actin) polymerized with the respective actin isoform was also ADP ribosylated, although the extent of the modification of F-actin was lower than that of globular actin (G-actin). In situ ADP ribosylation of beta/gamma-actin was evidenced with chicken peripheral heterophils permeabilized with saponin. Thus, the endogenous ADP ribosylation of actin in the heterophils may be involved in the cellular processes such as phagocytosis, secretion and migration. PMID- 1740141 TI - Purification and characterization of maize seedling casein kinase IIB, a monomeric enzyme immunologically related to the alpha subunit of animal casein kinase-2. AB - Casein kinase IIB (CKIIB), a protein kinase related to animal casein kinase-2 (CK2), has been purified to homogeneity. It appears to be a monomeric enzyme, composed by an individual 39 kDa subunit, homologous to the alpha/alpha' subunits of animal CK2 and devoid of the autophosphorylatable 25-kDa alpha subunit of animal CK2, which display an heterotetrameric alpha 2 beta 2/alpha alpha' beta 2 structure. Such a conclusion is supported by the following lines of evidence: (1) CKIIB displays an apparent 39,000 Mr by gel filtration on Ultrogel AcA 34 and it gives rise to a single prominent protein band of similar Mr (38,000) upon SDS/PAGE; (2) upon incubation of the enzyme with [32P]ATP, no radiolabeled bands are detectable which might be attributable to either canonical or atypical beta subunits; (3) the 39-kDa band immunoreacts with antisera that recognize the alpha subunit of rat and chicken CK2; (4) conversely, no component immunologically related with the beta subunit could be detected in CKIIB by Western-blot analyses with antisera that recognize animal beta subunits; (5) the recombinant beta subunit of human CK2 is readily phosphorylated by CKIIB, the reaction being prevented, rather than stimulated, by polylysine, a behaviour typical of animal CK2 autophosphorylation. While the responsiveness of CKIIB to either heparin inhibition or polylysine stimulation are reminiscent of those of animal CK2, its peptide substrate specificity is significantly different and its thermolability is increased. Altogether these data would indicate that maize seedling CKIIB represents a naturally occurring monomeric form of CK2 devoid of non-catalytic subunits. Its properties, compared to those of animal CK2, suggest that the beta subunits of animal CK2 may be responsible for structural modifications conferring an altered specificity and an increased stability to the catalytic subunit. PMID- 1740143 TI - H-NMR studies on d(GCTTAAGC)2 and its complex with berenil. AB - Two-dimensional (2D) 1H-NMR spectroscopy has been used to analyze the structure of d(GCTTAAGC)2 and its interaction with berenil in solution. Nuclear Overhauser enhancement connectivities enabled sequential assignments of nearly all proton resonances in the self-complementary octamer duplex and demonstrated that the oligonucleotide is primarily in a B-type conformation. No major conformational changes were observed by the addition of berenil, but proton resonances of the two adenosine nucleotides shifted substantially. Intermolecular nuclear Overhauser effects between berenil and the DNA duplex revealed that the drug binds via the minor groove of d(GCTTAAGC)2 in the A.T-base-pair region. At 18 degrees C the twofold symmetry of the duplex is preserved on berenil binding. However, strongly shifted proton resonances broadened significantly. A model is proposed for the berenil-d(GCTTAAGC)2 complex involving fast exchange of berenil between two equivalent symmetry-related binding sites, which span the 5'-TAA-3' region and are asymmetrically disposed with respect to the dyad axis of the duplex. These results are compared with previous studies on the berenil d(GCAATTGC)2 complex. PMID- 1740144 TI - 1H-NMR structural determination of the N-linked carbohydrate chains on glycopeptides obtained from the bean lectin phytohemagglutinin. AB - Phytohemagglutinin, the lectin of the common bean Phaseolus vulgaris, is a N linked glycoprotein with one high-mannose-type and one xylose-containing oligosaccharide side chain per polypeptide. The high-mannose-type glycan is attached to Asn12 and the complex-type glycan to Asn60 [Sturm, A. & Chrispeels, M. J. (1986) Plant Physiol. 81, 320-322]. The structures of the oligosaccharides were elucidated from two glycopeptides obtained from the lectin by Pronase digestion, affinity chromatography on concanavalin-A--Sepharose and gel filtration chromatography on a column of BioGel P-4. The N-linked glycan structures were investigated by 500-MHz 1H-NMR spectroscopy and were established to be: [formula; see text] PMID- 1740145 TI - A supramolecular light-harvesting complex from chloroplast photosystem-II membranes. AB - In this study, we report on the composition of a photosystem-II antenna preparation which contains three chlorophyll-a/b proteins (CP), CP29, CP24 and light-harvesting complex (LHC) II obtained from Zea mays grana membranes as previously described [Dainese, P. & Bassi, R. (1991) J. Biol. Chem. 266, 8136 8142]. We demonstrate that the three chlorophyll proteins are present in the preparation with a 3:3:9 molar ratio and that they form a supramolecular antenna complex which represents one third of the photosystem-II antenna system. Phosphorylation experiments show that this complex is involved in the mechanism of regulation of excitation-energy distribution between photosystems: phosphorylation of the membranes induces dissociation of the LHCII moiety from the CP29-CP24 moiety and changes in the aggregation state of LHCII components of the CP29-CP24-LHCII complex. The LHCII subpopulations of the complex are shown to be distinct from the total LHCII population by isoelectrofocusing analysis. On the basis of these data and in the light of the stoichiometry of photosystem-II chlorophyll-binding proteins, we propose a model for the organization of photosystem-II antenna system. PMID- 1740146 TI - Evidence for a selective destabilization of an integral membrane protein, the cytochrome b6/f complex, during gametogenesis in Chlamydomonas reinhardtii. AB - We studied the process of photosynthetic inactivation during gametogenesis of the unicellular green alga Chlamydomonas reinhardtii. We show that it is caused by the selective destabilization of a single transmembrane protein complex, the cytochrome b6/f complex, which is initially accumulated in the thylakoid membranes of vegetative cells. This protein destabilization is controlled by the intracellular energy sources available in the gametes, i.e. the coupled electron flow in the mitochondria and the amount of starch accumulated in the chloroplast. It nevertheless requires the expression of gamete-specific proteins. The loss of cytochrome b6/f complexes during gametogenesis is prevented by the addition of cycloheximide, but is chloramphenicol insensitive. Therefore, it is likely to involve some translation product of nuclear origin, specifically expressed during gametogenesis. Among the new polypeptides specifically found in the gametes, we detected a soluble polypeptide M alpha (approximate molecular mass of 63 kDa), which shared common epitopes with cytochrome f. Its synthesis displays an antibiotic sensitivity typical of a nuclear-encoded polypeptide and is controlled by the same intracellular signals which control the destabilization of the cytochrome b6/f complexes in the thylakoid membranes. PMID- 1740147 TI - Oxidoreduction of butanol in deermice (Peromyscus maniculatus) lacking hepatic cytosolic alcohol dehydrogenase. AB - In view of conflicting information in the literature regarding enzyme systems responsible for alcohol oxidation in deermice previously reported to lack hepatic alcohol dehydrogenase (ADH) activity, the reversibility of butanol oxidation was studied in vivo and in liver-perfusion systems. Mixtures of [1,1-2H2]ethanol and butanol were given intraperitoneally to deermice lacking (ADH-) or possessing (ADH+) ADH activity, followed by analysis of alcohols in blood by GC/MS. 2H exchange between the two alcohols was seen in all experiments. In ADH- deermice, the 2H excess of butanol increased steadily and reached 18 +/- 5% after 2.5 h. In ADH+ deermice, butanol was rapidly eliminated and the 2H excess was about 7% after 0.5 h. In similar experiments with rats, the 2H excess was about 40% for 2 h. Perfusions of livers from ADH- deermice with mixtures of unlabelled and 1 [2H]butanol showed significant but slow intermolecular hydrogen transfer at C1, indicating oxidoreduction catalyzed by a dehydrogenase. Slow reduction of butanal was observed in mitochondria from ADH- deermice. ADH activity with a pH optimum of 10 and Km for ethanol of 6 mM was detected in the inner mitochondrial membranes from rats and deermice. However, low rates of oxidation observed in experiments carried out with perfused livers and in vitro suggest that this enzyme system does not contribute significantly to alcohol oxidation in vivo. Thus, perfused liver from ADH- deermice appears to be a useful system for studies of ADH-independent oxidation of alcohols. The 2H exchange between the alcohols seen in vivo indicates that both ethanol and butanol are substrates for a common extrahepatic dehydrogenase in ADH- deermice. PMID- 1740148 TI - Mechanism of the stimulatory effect of a potassium-rich medium on the phosphorylation of glucose in isolated rat hepatocytes. AB - We have investigated the mechanism by which the replacement of a Na(+)-rich medium by a K(+)-rich medium causes an increase in the apparent affinity of glucokinase (hexokinase IV or D) for glucose in isolated hepatocytes [Bontemps, F., Hue, L. & Hers, H. G. (1978) Biochem. J. 174, 603-611]. The stimulatory effect of a K(+)-rich medium on the rate of glucose phosphorylation, as assessed by the release of tritium from [2-3H]glucose, was only partially additive with the effect of fructose, suggesting that it was also due to a decrease in the inhibition exerted on glucokinase by its regulatory protein. Measurements of metabolites indicated that the effect of the K(+)-rich medium was neither due to the formation of fructose 1-phosphate, nor to changes in the concentrations of fructose 6-phosphate or Pi, two other effectors of the regulatory protein. Replacement of Na+ by K+ in the medium resulted in a time-dependent and dose dependent increase in cell volume that paralleled the changes in the rate of detritiation observed at 5 mM glucose. The water and chloride contents, estimated using radiolabelled compounds, were threefold and tenfold higher, respectively, in K+ cells than in Na+ cells, and the intracellular Cl- concentration about threefold higher (94 versus 29 meq/l). The effects of the K(+)-rich medium on cell volume, Cl- concentration and rate of detritiation were greatly reduced by including 80 mM trehalose or sucrose in the medium at the start of the incubation. Addition of trehalose to cells incubated for 45-50 min in the K(+) rich medium caused an immediate decrease in cell volume whereas the rate of detritiation and the Cl- concentration underwent a transient increase followed by a decrease. Replacement of KCl by KBr, potassium acetate or potassium trichloroacetate in the K(+)-rich medium resulted in different relationships between cell volume and the rate of detritiation, in agreement with the differential effect of these salts on the activity of purified glucokinase assayed in the presence of regulatory protein. From these results we conclude that the increase in the activity of glucokinase induced by a KCl-rich medium is at least partly due to an increase in the concentration of Cl-, which relieves the inhibition exerted by the regulatory protein on purified glucokinase. PMID- 1740149 TI - Characterisation of a cysteine protease from bloodstream forms of Trypanosoma congolense. AB - A cysteine protease (trypanopain-Tc) with cathepsin-L-like properties has been purified from Trypanosoma congolense. The enzyme has an apparent molecular mass of 31-32 kDa by SDS/PAGE and 66 kDa by gel chromatography. It has a pI 7.4 and a high affinity for concanavalin A. Trypanopain-Tc catalyses the limited proteolysis of a variety of protein substrates such as fibrinogen, serum albumin and trypanosome variant-surface glycoprotein. It has minimal or no activity against casein or elastin. A variety of peptidyl amidomethylcoumarins and peptidyl diazomethanes were used to test the specificity of trypanopain-Tc. The better substrates had Arg or Lys in P1 and hydrophobic amino acids in P2 and P3. The best substrate found for trypanopain-Tc was Z-Phe-Arg-NHMec (Z, benzyloxycarbonyl; NHMec, 7-amido-4-methylcoumarin). The kinetic constants for the hydrolysis of Z-Phe-Arg-NHMec were kcat = 17.4 s-1, Km = 4.4 microM, kcat/Km = 4.0 microM-1.s-1, which are very similar to those of cathepsin L with this substrate. The specific substrates for cathepsin B (Z-Arg-Arg-NHMec) and cathepsin H (Arg-NHMec) were not hydrolysed by trypanopain-Tc under the conditions tested. The pH optimum of trypanopain-Tc against Z-Phe-Arg-NHMec was pH 6.0 but it showed a broad peak of activity extending well into the alkaline region. The enzyme was activated by low-molecular-mass thiol compounds and inhibited by cystatin, L-trans-epoxysuccinyl-4-guanidinobutane (E-64) and a variety of peptidyl diazomethanes. The most effective diazomethane inhibitors (Z Leu-Leu-Met-CHN2, Z-Leu-Met-CHN2 and Z-Leu-Lys-CHN2, were inhibitory at nanomolar concentrations and were trypanocidal in vitro after 24-48 h incubation in greater than or equal to 20 microM [inhibitor]. However, it is not clear whether the trypanocidal activity of these inhibitors is a consequence of the inhibition of trypanopains or of some other essential proteolytic activities within the parasites. PMID- 1740150 TI - Purification and characterization of cathepsin J from rat liver. AB - Cathepsin J has been partially purified [Liao, J. C. R. & Lenney, J. F. (1984) Biochem. Biophys. Res. Commun. 124, 909-916], but its detailed properties are still unknown. In this study, we have purified cathepsin J completely and characterized it. It was purified to homogeneity from the mitochondrial-lysosomal fraction of rat liver by acid treatment, followed by ammonium sulfate precipitation (20-65%), and chromatographies on S-Sepharose, ConA-Sepharose, Affi gel 501, HPLC DEAE-5PW and HPLC TSK G3000SW. Cathepsin J was found to be a lysosomal high-molecular-mass cysteine protease of about 160 kDa consisted of two different subunits. One subunit (alpha subunit) was a glycoprotein with a molecular mass of 19-24 kDa which was reduced to 19 kDa by treatment with endoglycosidase F. It has the amino acid sequence LPESWDWRNVR at its N-terminus, which was very similar to those at the N-termini of rat cathepsins B, H and L. The other subunit (beta subunit) was a glycoprotein with a molecular mass of 17 kDa, which was reduced to 14 kDa by treatment with endoglycosidase F. It had DTPANETYPDLLG at its N-terminus, which had no similarity with the N-terminal sequences of other cathepsins. Cathepsin J showed strong affinity for synthetic substrates such as N-benzyloxycarbonyl-phenylalanyl-arginine 4-methyl-coumaryl-7 amide and glycyl-arginine beta-naphthylamide. It was activated by thiol reagents and chloride ion and was inhibited by cysteine protease inhibitors. However, its initial inhibition constant Ki(initial) by N-(L-3-trans-carboxyoxirane-2 carbonyl)-L-leucine-3- methylbutylamide (E-64-c) was 1800 nM, which was 100-500 times those of cathepsins B and L. Many properties of cathepsin J were similar to those of cathepsin C (dipeptidylaminopeptidase I) reported as a lysosomal cysteine protease with dipeptidyl-aminopeptidase activity [McDonald, J. K., Reilly, T. J. & Ellis, S. (1964) Biochem. Biophys. Res. Commun. 16, 135-140]. Furthermore, antiserum against rat liver cathepsin C reacted with rat liver cathepsin J. These findings suggested that cathepsin J is identical with cathepsin C. PMID- 1740151 TI - 6-Deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme. AB - Sequencing of the eryA region of the erythromycin biosynthetic gene cluster from Saccharopolyspora erythraea has revealed another structural gene (ORF B), in addition to the previously characterised ORF A, which appears to encode a component of 6-deoxyerythronolide-B synthase, the enzyme that catalyses the first stage in the biosynthesis of the polyketide antibiotic erythromycin A. The nucleotide sequence of ORF B, which lies immediately adjacent to ORF A, has been determined. The predicted gene product of ORF B is a polypeptide of 374417 Da (3568 amino acids), which is highly similar to the product of ORF A and which likewise contains a number of separate domains, each with substantial amino acid sequence similarity to components of known fatty-acid synthases and polyketide synthases. The order of the predicted active sites along the chain from the N terminus is 3-oxoacyl-synthase--acyltransferase--acyl-carrier-protein-- 3-oxoacyl synthase--acyltransferase--dehydratase--enoylreductase-- oxoreductase--acyl carrier-protein. The position of the dehydratase active site has been pinpointed for the first time for any polyketide synthase or vertebrate fatty-acid synthase. The predicted domain structure of 6-deoxyerythronolide-B synthase is strikingly similar to that previously established for vertebrate fatty-acid synthases. This analysis of the sequence supports the view that the erythromycin-producing polyketide synthase contains three multienzyme polypeptides, each of which accomplishes two successive cycles of polyketide chain extension. In this scheme, the role of the ORF B gene product is to accomplish extension cycles 3 and 4. PMID- 1740152 TI - CecC, a cecropin gene expressed during metamorphosis in Drosophila pupae. AB - Cecropins are antibacterial peptides, induced in insects in response to bacterial infections. In Drosophila, three cecropin genes have previously been characterized, CecA1, CecA2, and CecB, in a dense cluster at 99E on the third chromosome. From the same locus, we now describe a fourth member of the cecropin gene family, CecC, which is mainly expressed at the early pupal stage. In situ hybridization to immunized pupae show that CecC is induced in the anterior end of the larval hindgut and in other larval tissues that are undergoing histolysis. Within these other tissues it is often expressed in distinct foci that may correspond to hemocytes. A similar pattern of expression in the metamorphosing pupa is also observed for the CecA and CecB genes. Comparing the DNA sequences of the cecropin genes, a conserved region is observed about 30 bp upstream of the TATA box. It consists of three shorter motifs, two of which are reminiscent of a putative promoter element in immune protein genes from the cecropia moth. PMID- 1740153 TI - The phosphorylated and/or sulfated structure of the carbohydrate-protein-linkage region isolated from chondroitin sulfate in the hybrid proteoglycans of Engelbreth-Holm-Swarm mouse tumor. AB - The structure of the linkage region of chondroitin sulfate chains attached to the hybrid proteoglycans of the Engelbreth-Holm-Swarm mouse tumor was investigated. The peptidoglycan fraction which contains oversulfated chondroitin sulfate rich in the GlcA beta 1-3GalNAc-4,6-diO-sulfate unit and undersulfated heparan sulfate rich in GlcA beta 1-4GlcNAc and GlcA beta 1-4GlcN-2N-sulfate units was isolated after exhaustive protease digestion of the acetone powder of the tumor tissue, (GlcA, glucuronic acid; GalNAc, 2-deoxy-2-N-acetylamino-D-galactose). Glycosaminoglycans were released by beta-elimination using NaB3H4 and digested with chondroitinase ABC. The linkage region fraction was separated from heparan sulfate by gel filtration and fractionated by HPLC on an amine-bound silica column. Six radiolabeled compounds (L1-L6) were obtained and structurally analyzed by cochromatography with authentic hexasaccharide alditols recently isolated by us from the linkage region, and by digestion using chondroitinase ACII, alkaline phosphatase and beta-galactosidase in conjugation with HPLC. These compounds shared the conventional hexasaccharide backbone structure: delta GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol, (delta GlcA, delta 4.5-GlcA or D-gluco-4-enepyranosyluronic acid). L1 was not sulfated or phosphorylated. L2 and L4 were monosulfated at C-6 and C-4 of the GalNAc residue, respectively. Upon alkaline phosphatase digestion, L3, L5 and L6 were converted to L1, L2 and L4, respectively. Analysis of the periodate oxidation products indicated that the phosphate group in L3, L5 and L6 is located at C-2 of Xyl-ol. These results suggest that Xyl-2-O-phosphate is associated with both 4-O-sulfated and 6-O-sulfated GalNAc units and does not directly determine the sulfation pattern of chondroitin sulfate. PMID- 1740154 TI - Zonation of cytochrome P450 isozyme expression and induction in rat liver. AB - The regional expression of six different cytochrome P450 (CYP) forms in rat liver under constitutive and induced conditions was compared using immunological techniques. Immunostaining of consecutive thin sections from control liver revealed that the same hepatocytes, forming a 6-8 cells thick layer surrounding the terminal hepatic venules, were stained for CYP2B1/2, CYP2E1 and CYP3A1. Staining of CYP2A1 extended further into the midzonal region, whereas all cells of the acinus stained for CYPEtOH2. These results were supported by Western blot analysis of cell lysates from the periportal or perivenous region obtained by zone-restricted digitonin treatment during in situ perfusion. The data suggest three distinct patterns of constitutive P450 expression: perivenous-restricted (CYP2B1/2, CYP2E1 and CYP3A1); perivenous-dominated (CYP2A1) and panacinar (CYPEtOH2). Chronic exposure to ethanol caused induction of CYP2E1 in the same cells already being constitutively expressed, whereas CYPEtOH2 was more induced in the periportal area. The relative induction of CYP2B1/2, CYP3A1 and CYPEtOH2 after treatment with phenobarbital was stronger in periportal hepatocytes, resulting in levelling out of the initial perivenous dominance of CYP2B1/2 and CYP3A1, whereas CYPEtOH2 became periportal-dominated. Acetone induced CYP2E1, CYP2C11 and CYP3A1 selectively in the perivenous area. These studies indicate that a particular P450 isozyme is generally induced in the same cells where it is constitutively expressed, and that this regional selectivity is independent of the kind of inducer. The data suggest that, during maturation, the hepatocytes acquire various phenotypes in the periportal and perivenous region, to respond differently to endogenous and exogenous signals in the control of P450 expression. PMID- 1740155 TI - The molecular and genetic analysis of mouse development. AB - This review describes some recent advances in the molecular-genetic analysis of mouse development. Reversed genetics and gene assignment have been used to isolate genes affected in developmental mutations. The establishment of a high density molecular-genetic map promises to facilitate cloning of additional genes with developmental functions. Based on molecular, biochemical or other biological criteria many mouse genes that code for transcriptional regulators, growth-factor like molecules and their receptors have been isolated. The role of these genes during development can be analysed in vivo after producing targeted mutations. Mutations can be generated by homologous recombination in the genome of embryonic stem cells and can then be introduced into the mouse germ line by means of germ line chimaeras. Additional approaches employing stem cells to identify and mutate putative developmental genes are coming into use. PMID- 1740156 TI - Analysis of genes involved in the biosynthesis of lantibiotic epidermin. AB - The structural gene of the lanthionine-containing peptide antibiotic epidermin is located on a 54-kb plasmid of Staphylococcus epidermidis [Schnell et al. (1988) Nature 333, 276-278]. A 13.5-kb DNA region neighbouring the epidermin structural gene (epiA) was subcloned and its sequencing revealed five additional open reading frames. Three of these reading frames, epiB, epiC and epiD shared no homology with previously described proteins stored in data bases. They were located 3' adjacent to epiA. Using epiB as a probe, a 5-kb mRNA was identified indicating that three or all four reading frames are transcribed as an operon. Additionally, a 0.3-kb mRNA specific for epiA was identified. Two open reading frames (epiP and epiQ) were located 3' to epiA, epiB, epiC and epiD, but in the reverse orientation. The epiQ gene product shows similarity to the positive regulatory factor PhoB. This might indicate a regulatory function of epiQ in epidermin biosynthesis. The epiP gene product shows striking similarity to several serine proteases which makes epiP a likely candidate for processing the epidermin prepeptide. Heterologous epidermin synthesis in the non-producing organism Staphylococcus carnosus finally proved that these reading frames are necessary for epidermin biosynthesis. PMID- 1740157 TI - Anthracycline binding to DNA. High-resolution structure of d(TGTACA) complexed with 4'-epiadriamycin. AB - Crystallographic methods have been applied to determine the high-resolution structure of the complex formed between the self-complementary oligonucleotide d(TGTACA) and the anthracycline antibiotic 4'-epiadriamycin. The complex crystallises in the tetragonal system, space group P4(1)2(1)2 with a = 2.802 nm and c = 5.293 nm, and an asymmetric unit consisting of a single DNA strand, one drug molecule and 34 solvent molecules. The refinement converged with an R factor of 0.17 for the 2381 reflections with F greater than or equal to 3 sigma F in the resolution range 0.70-0.14 nm. Two asymmetric units associate such that a distorted B-DNA-type hexanucleotide duplex is formed incorporating two drug molecules that are intercalated at the TpG steps. The amino sugar of 4' epiadriamycin binds in the minor groove of the duplex and displays different interactions from those observed in previously determined structures. Interactions between the hydrophilic groups of the amino sugar and the oligonucleotide are all mediated by solvent molecules. Ultraviolet melting measurements and comparison with other anthracycline-DNA complexes suggest that these indirect interactions have a powerful stabilising effect on the complex. PMID- 1740158 TI - The amino acid sequence of glutamate decarboxylase from Escherichia coli. Evolutionary relationship between mammalian and bacterial enzymes. AB - The amino acid sequence of glutamate decarboxylase from Escherichia coli was solved by a combination of automated Edman degradation of peptide fragments derived by proteolytic and chemical cleavage and sequencing of DNA. Correct alignment of three peptides, for which no peptide overlaps were available, was achieved by sequencing a 1.1-kbp fragment of DNA produced by a polymerase-chain reaction using primers corresponding to sequences known to be in amino-terminal and carboxy-terminal regions of the protein. Sequence similarity (24% identity) with mammalian glutamate decarboxylase was found to be limited to a 55-residue sequence around the lysine residue that binds the coenzyme. Stronger similarity (38% identity), again confined to the same region, is seen with bacterial pyridoxal-phosphate-dependent histidine decarboxylase. PMID- 1740159 TI - The piscine plasma retinol-binding protein. Purification, partial amino acid sequence and interaction with mammalian transthyretin of rainbow trout (Oncorhynchus mykiss) retinol-binding protein. AB - 1. Retinol-binding protein (RBP) has been isolated from the pooled plasma or rainbow trouts (Oncorhinchus mykiss) by gel filtration, hydrophobic interaction chromatography and ion-exchange chromatography. By this procedure two forms of the protein, both with a molecular mass (approximately 20 kDa) similar to that of mammalian RBP, were purified to homogeneity. Five amino acid substitutions have been found in the partial (about 60%) sequences of the two forms of trout RBP, which are presumably acetylated at their N terminus. The apparent participation of six conserved cysteines in the formation of disulphide bridges, as in human RBP, and the similarity (about 60%) of the amino acid sequence of trout and mammalian RBPs, indicate the existence of a similar overall structure organization in evolutionary distant RBPs. 2. Although the two forms of trout RBP are not physiologically involved in the formation of any protein--protein complex in plasma, they are capable of interacting with mammalian transthyretin, albeit with a binding affinity (K'd = 15-40 microM) considerably lower than that of mammalian RBP. Our data indicate that the two forms of trout RBP also possess the region that in mammalian RBP has the functional role of binding transthyretin. It is suggested that transthyretin (or a homologous protein) was modified, during phylogenetic development of the non mammalian vertebrates, to acquire a binding site for such a region of the RBP molecule. PMID- 1740160 TI - [Review: development of the spontaneously epileptic rat]. PMID- 1740161 TI - [Number of animals used in experiments in 1990--results of a survey--JALAS Working Group for Laboratory Animal Data Bank, Tokyo and Life Science Research Information Section, The Institute of Physical and Chemical Research, Saitama]. AB - A survey on the number of animals used in experiments including bioassay, diagnosis, education and preparation of biological agents such as vaccine between April 1990 and March 1991 was conducted. Out of 849 universities, institutes, testing laboratories and companies, 607 replies were received. The distribution of the number of animals is shown in the following tables. [tables; see text] PMID- 1740162 TI - [Changes in rhythmicity of ambulatory and drinking activities produced by presentation of short time lightings during dark period in rats]. AB - It is well known that the lighting conditions affect many physiological phenomenon of laboratory animals. However, lighting conditions are frequently disturbed by investigators themselves. In this study, behavioral (ambulation and drinking) rhythmicities of rats were investigated after irregular lighting; i. e. presentation of short time lighting at 21:00, 24:00 and 3:00 for 12 min during dark period (18:00-6:00). Vaginal smear was taken and sexual cycle was observed everyday. Ambulatory and drinking activities were measured by Gundai type Ambulo drinkometer. The irregular lighting produced the following changes in the rhythmicities: 1) increase in the ambulatory activity during 15:00-18:00 immediately before dark period 2) decrease in ambulatory activity before ovulation 3) disappearance of inhibitory phenomenon of drinking activity which was usually observed before ovulation 4) increase in the drinking activity during 6:00-9:00 immediately after dark period 5) the changes in rhythmicities of the behavioral activities lasted for more than 1 month after replacement to the regular lighting condition. PMID- 1740163 TI - Dotted white--a plumage color mutant in Japanese quail (Coturnix coturnix japonica). AB - A plumage color mutant, dotted white (DTW), of Japanese quail is described in this paper. The adult DTW mutant shows white plumage with a small colored spot on the head and/or back. The pigmented spots invariably appear on the dorsal region and never on the ventral region of the body. Some birds lack colored spots and show pure white plumage. The chick of the DTW mutant shows cream yellow plumules similar to those of the White Leghorn chick. Colored spots also exist as in adults, and its coloration is diluted light brown. The feathers on colored spots of the adult show diluted pigmentation as compared with wild-type feathers. In addition, the wheat-straw colored shaft streak is extremely narrow and the transversal bars are missing. The DTW mutant is thought to be genetically different from previously reported similar mutants, brown-splashed white, panda, and recessive white. Genetic analyses revealed that the DTW mutant plumage is controlled by an autosomal recessive gene. The gene symbol dtw is provisionally proposed, since there remains a possibility that the DTW character may be allelic to some of the similar mutant characters mentioned above. PMID- 1740164 TI - [Fertilizing ability in vitro of golden hamster spermatozoa after acute testicular X-irradiation]. AB - The present study is concerned with the effect of radiation to the testis on fertilizing ability in vitro using golden hamster spermatozoa. Male hamsters at 6 and 8 weeks of age were given acute testicular X-irradiation (200 kVp, 20 mA, 0.47-0.48 Gy/min). Spermatozoa were collected from the cauda epididymides at different times after irradiation and then they were suspended in fertilization medium. After preincubation for 4-5 hr, the spermatozoa were cultured with the eggs collected from mature hamsters treated with PMSG-hCG. Fertilized eggs were examined for incidence of sperm penetration and formation of pronuclei at 4-5 hr after insemination. The fertilization rate (47.7%) at the 6th week after irradiation with a dose of 2 Gy was much lower in comparison with the control value (92.6%). However, the fertilization rates at the 3rd and 9th weeks after irradiation were 97.7 and 90.6%, respectively. In these period, no difference was found between the irradiated groups and the control groups. From the changes in sperm concentration after irradiation with a dose of 2 Gy, it was found that the fertilization rate was the lowest at the 6th week. The sensitive stage to radiation during spermatogenesis with reference to the reduction of fertilizing ability after irradiation coincides with that of decrease in the sperm concentration and sperm motility. The results of fertilization rate at the 6th week after different doses of X-irradiation (0.25-6 Gy) indicated that the reduction of fertilization rate is nearly expressed as a dose-response relationship.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740165 TI - A method to eliminate odor from recirculating air in the animal house. AB - A new method to eliminate odors from air recirculating in an animal house is described. The new system consists of an ozonizer and titania silica ozone decomposition catalyst in the terminal of a recirculating ventilation system. The principle underlying the elimination of odors is the oxidative reaction of malodorous components on the surface of the catalyst caused by coupling with ozonolysis. This method appeared superior in terms of its durability, efficiency and lack of resistance to air flow. PMID- 1740166 TI - Turnover rates of hypothalamic dopamine associated with the two types of prolactin surges during pseudopregnancy in rats. AB - Two surges of prolactin (PRL) are observed daily during pseudopregnancy (PSP) in the rat: the nocturnal (N) surge at dawn and the diurnal (D) surge in the evening. In order to clarify differences in the controlling mechanisms of the two types of PRL surges, we attempted to examine the turnover rates of dopamine (DA) and norepinephrine (NE) in the preoptic-anterior hypothalamus (PAH) and mid posterior hypothalamus (MPH) on day 5-6 of PSP. The turnover rates of DA in the hypothalamus were inversely correlated with the serum PRL levels at the D surge when a significant increase in serum PRL was accompanied by not only a marked decrease in turnover rates of DA in the PAH, but also a slight decrease in turnover rates of the amine in the MPH. Contrarily, no significant decrease occurred in the turnover rates of DA in the hypothalamus at the N surge. There was no obvious correlation between the turnover rates of NE in the hypothalamus and the serum PRL levels at either PRL surge. These findings suggest that decreased turnover rates of DA in the hypothalamus are involved in the D surge, and it is most probable that the N PRL surge occurs under the control of another factor such as the hypothalamic PRL-releasing factor. PMID- 1740167 TI - Pathology and angiographical studies on urogenital organ system induced by idiopathic hemorrhage in male E1 mice. AB - Urogenital organ system induced by idiopathic hemorrhage in sudden died male E1 mice were investigated macro- and histopathologically and angiographically. The mortality of the male E1 mice with brief life span was 85% during observation period for 33 weeks, and about half of the male E1 mice died between 10-week-old and 20-week-old. In all dead mice, urine retention was prominent, and the seminal vesicle or the coagulating gland, especially the bulbocavernosus muscle had severe hemorrhage. There was coagulated blood mass in the urethral lumen and the lumen of the seminal vesicle and the coagulating gland. Further, in pars spongiosa, coagulated blood mass occupied the most area of the corpus spongiosum penis and corpus cavernosum penis with severe hemorrhage. Angiographically, the penile artery in not affected male E1 mice was thinner than that in control mice. PMID- 1740168 TI - [The application of industrial endoscope to observation of the ocular-fundus in small laboratory animals]. AB - Observation and recording methods of the ocular-fundus in small laboratory animals were studied using the industrial endoscope and VTR systems, respectively. The ocular-fundus was observed widely, brightly and clearly in the usual animal facility. In addition, the ocular-fundus was recorded easily and it was possible to examine the ocular-fundus recorded by the VTR systems. PMID- 1740169 TI - Effects of atherogenic diet on young farm pigs. AB - This study was designed to assess the usefulness of young farm pigs as an experimental model for hypercholesterolemia. In order to test this, we investigated both serologic and electrocardiographic effects of atherogenic diet. Four-week-old pigs were fed an atherogenic diet for 8 weeks. No arrhythmia was observed on ECG in all animals. There were no significant difference between control and atherogenic diet group on the values of ECG parameters. However, plasma lipids values of atherogenic diet group were significantly (p less than 0.05) higher than those of control diet group. Thus, hypercholesterolemia was induced in young farm pigs by feeding atherogenic diet in a relatively short time. This fact suggests that young farm pigs may be an useful model for further studies of the effect of hypercholesterolemia on cardiovascular function and the early pathogenesis of atherosclerosis. PMID- 1740170 TI - Effects of naloxone and naltrexone on receptive and proceptive behaviors in female rats. AB - The sexual receptive and proceptive behaviors induced by opiate antagonists, naloxone and naltrexone in estrogen-primed ovariectomized rats were observed under the presence of sexually active males. The females were treated intraperitoneally with naloxone or naltrexone at doses ranging from 0.5 to 4.0 mg/kg and the sexual behavior of females was tested before and after the injection of drug. The results obtained suggest that the opiate antagonists play a role in the regulation of lordosis behavior, but not proceptive behavior in female rats. PMID- 1740171 TI - [Spontaneous cleft palate in CF#1/Ohu mice]. AB - We found a spontaneous cleft palate in a mouse of CF#1/Ohu (Ohu University, Japan). Further, the frequency of the spontaneous cleft palate in strains of CF#1/Jms (Institute of Medical Science, University of Tokyo, Japan) and CF#1/Jah (National Institute of Animal Health, Japan) were about 3%, respectively. The frequency and the types of spontaneous cleft palate in CF#1 were clearly different from those in A/J and CL/Fr strains which were used as model animals of lip and cleft palate. We think that CF#1 is the new animal models to analyze a cleft palate genetically and biochemically. PMID- 1740172 TI - [Improvement of pituitary homograft under the kidney capsule in mice]. AB - The model of hyperprolactinemia induced by pituitary homografts under the kidney capsule has been used mainly in the field of reproductive physiology. The authors report an improved method for pituitary grafting in mice. The procedure was as follows: 1. The male pituitary glands with normal saline were aspirated into a polyethylene tube. 2. Two incisions were made in the kidney capsule. 3. The polyethylene tube with pituitary glands was inserted via a large incision. 4. Blowing air into the tube, the pituitary glands were left under the kidney capsule and normal saline streamed out of a small incision. Using this method, all pituitary grafted mice became pseudopregnant. PMID- 1740173 TI - Changes in rhythmicities of ambulatory and drinking activities after hypophysectomy in rats. AB - Effects of hypophysectomy on circadian rhythms of ambulatory and drinking activities in adult male rats were automatically recorded and investigated with a Gundai-type ambulodrinkometer. The rats were maintained under LL conditions following an LD condition. When free-running rhythms had stabilized, the rats were hypophysectomized. The rhythmicities of both activities became indistinct over the 2-4 weeks following surgery, and then gradually recovered. At this time phase shifts (phase advance) were observed in the hypophysectomized rats, while these changes were not observed in sham-operated rats. All rats entrained to lighting when kept under LD conditions again. These results suggest that the pituitary does not play an essential role in maintaining circadian rhythms, but does function as an important subordinal oscillator. PMID- 1740174 TI - Trypanosoma cruzi: stage expression of calmodulin-binding proteins. AB - The subcellular distribution of calmodulin-binding proteins in three life stages of Trypanosoma cruzi was analyzed by a [125I]calmodulin gel overlay procedure under conditions where proteolysis was kept to a minimum. It was found that T. cruzi contains a complex profile of calcium-dependent calmodulin-binding proteins and that several of these polypeptides were differentially expressed at specific stages of development. The majority of these stage-specific polypeptides was found in the particulate fractions of the replicative stages of the parasite, i.e., epimastigote and amastigote. These studies suggest that calcium and calmodulin may play an important central role in the growth and differentiation of this parasite. We have also assessed the calmodulin content of the various life stages by immunoblot analysis. These studies identified a 14-kDa immunoreactive peptide present at equivalent levels in epi-, trypo-, and amastigote stages (extracellular). PMID- 1740175 TI - Plasmodium chabaudi: association of reversal of chloroquine resistance with increased accumulation of chloroquine in resistant parasites. AB - The effects of tricyclic antidepressants, desipramine and imipramine, and phenothiazines, chlorpromazine and trifluoperazine, on chloroquine (CQ)-resistant and CQ-sensitive lines of P. chabaudi were examined in vivo. In mice that received daily injections of these drugs the growth of CQ-resistant and CQ sensitive parasites was unaffected or affected very slightly, if at all. A combination of CQ and each drug suppressed the growth of CQ-resistant parasites in a dose-dependent manner. In addition, in CQ-sensitive parasites each drug also increased the susceptibility to CQ. Measurements of CQ levels by high-performance liquid chromatography showed that CQ accumulated in sensitive parasites to more than twice the level in resistant parasites at 2 to 4 hr after an injection of CQ. Verapamil and desipramine substantially increased CQ levels in both CQ resistant and CQ-sensitive parasites. These results suggest that not only Ca2+ antagonists but tricyclic antidepressants reverse CQ resistance in CQ-resistant parasites and enhance the inhibitory effect in sensitive parasites by increasing CQ levels in those parasites. The effects of Ca2+ antagonists, tricyclic antidepressants, and phenothiazines on a pyrimethamine-resistant line of P. chabaudi were also studied. None of the Ca2+ antagonists (verapamil, nicardipine, and diltiazem) affected the growth of the parasite in combination with 20 mg/kg pyrimethamine. Tricyclic antidepressants and phenothiazines suppressed pyrimethamine-resistant parasites to some extent. However, the extent of this suppression was less pronounced as compared with that of suppression of CQ resistance by the same drugs. PMID- 1740176 TI - Schistosoma japonicum: excretory-secretory products of the eggs during miracidial development. AB - The release pattern of excretory-secretory (E-S) products of Schistosoma japonicum eggs was investigated using eggs cultured in a chemically defined medium (MEMSE-J) for 16 days. The amount of protein released in culture supernatants was greater in 0- to 4-day and 12- to 16-day cultures than in 4- to 12-day cultures. The protein composition of E-S products and soluble extracts of newly laid eggs (N-SEA) and in vitro matured eggs (M-SEA) was analyzed by SDS PAGE. Silver staining patterns of N-SEA and M-SEA were found to be similar except for the band at approximately 66 kDa, which appeared in highest concentrations in N-SEA. Western blot analysis with human infected sera showed antibody recognition of a 140- to 160-kDa antigen present in E-S products from mature eggs, while E-S products from immature eggs were unreactive. When either [35S]methionine or [3H]glucosamine was added to the culture medium, newly synthesized proteins or glycoproteins of the SEA and E-S products were labeled. Incorporation of both isotopes into SEA appears to correlate with developmental activity of the eggs. In contrast, release of E-S proteins and glycoproteins is more apparent as the miracidium matures. These results suggested that the source of E-S products from immature eggs is likely to be the collapsing vitelline cells and that of E-S products from mature eggs to be mainly miracidial secretions. PMID- 1740177 TI - Loss of Lyme disease spirochetes from Ixodes ricinus ticks feeding on European blackbirds. AB - To determine whether blackbirds (Turdus merula), the most abundant and most abundantly tick-infested ecotonal bird of Central Europe, may contribute to the transmission of the Lyme disease spirochete (Borrelia burgdorferi), we compared the infectivity to ticks of naturally as well as experimentally infected blackbirds and rodents. European blackbirds experience intense exposure to Ixodes ricinus ticks and to the pathogens that they transmit. In nature, subadult I. ricinus ticks found feeding on these birds generally contain no spirochetes, although infection is universal in those found on black-striped mice (Apodemus agrarius). Those found on yellow-necked mice (A. flavicollis) are less frequently infected. Ticks lose infection in the course of feeding on blackbirds and fail to infect them. Subadult I. ricinus ticks readily feed on blackbirds, black-striped mice, and jirds (Meriones unguiculatus), but engorge less fully on the bird than on the rodents. Although birds may burden human health by establishing new infestations of I. ricinus ticks, our observations indicate that particular birds may benefit health by locally diminishing transmission of the Lyme disease spirochete. PMID- 1740178 TI - Leishmania amazonensis infection: a comparison of in vivo leishmanicidal mechanisms between immunized and naive infected BALB/c mice. AB - In vitro studies have shown that both macrophage activation and destruction of parasitized macrophages lead to leishmania destruction. The relative role played by such mechanisms in vivo have not been properly evaluated. We took advantage of the model of intravenous immunization with solubilized leishmanial antigen which renders partially resistant the otherwise highly susceptible BALB/c mice to address this issue avoiding the interference of different genetic backgrounds. Leishmania destruction occurred in three situations: destruction of the parasitized macrophage, which were in close contact with lymphocytes or eosinophils; extracellular damage, always surrounded by small foci of granulocytes; and parasite damage inside activated macrophages. Destruction of the parasitized macrophages was frequently seen in immunized and protected animals. Our observations suggest that destruction of parasite-loaded macrophages is an important mechanism of host protection in experimental cutaneous leishmaniasis. PMID- 1740179 TI - Leishmania donovani: antagonistic effect of S-adenosyl methionine on ultrastructural changes and growth inhibition induced by sinefungin. AB - Sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent in vitro and in vivo (Bachrach et al. 1980, FEBS Letters 121, 287-291; Neal et al. 1985, Transactions of the Royal Society of Tropical Medicine and Hygiene 79, 85-122). It was previously shown that this molecule is a competitive inhibitor of AdoMet for transmethylases (Paolantonacci et al. 1986, Molecular and Biochemical Parasitology 21, 47-54; Avila et al. 1987, Molecular and Biochemical Parasitology 26, 69-76) and that it induces shape changes of Leishmania donovani promastigotes as observed by light microscopy (Lawrence and Robert-Gero 1990; Bulletin de la Societe Francaise de Parasitologie 8, 13-18). In the present work the effect of the antibiotic on the ultrastructure was analyzed by electron microscopy. The main changes induced at sublethal concentrations (0.26 microM sinefungin for 16 hr) were progressive rounding, decreased motility, enlargement of the flagellar pocket, and shortening and loss of the external part of the flagellum. The comparison with control cells showed shorter Golgi saccules and fragmentation of the trans-Golgi network into vesicles, indicating a stimulated Golgi apparatus activity. This result, associated with the enlarged flagellar pocket, suggests an unbalanced cytoplasmic exchange between exocytosis and endocytosis. These effects are quite different from those induced by tunicamycin (Dagger et al. 1984, Biology of the Cell 50; 173-180) or paromomycin. In addition, other nucleoside and nonnucleoside growth inhibitors failed to induce similar changes. AdoMet antagonized the sinefungin induced shape changes and ultrastructural modifications but had no effect with respect to other growth inhibitors. This suggests that the sinefungin activity at the cellular level is specifically related to competition with AdoMet. A comparative study of N-methylation and carboxylmethylation of proteins in sinefungin-treated promastigotes showed that the antibiotic preferentially inhibits the latter, catalyzed by protein-O-methyltransferases. These enzymes are known to regulate the function of various proteins involved in secretion. Overall the results suggest that one of the main targets of sinefungin in exponentially growing cells is the protein carboxylmethylation involved in membrane transport. PMID- 1740180 TI - Biochemical characterisation of the enzyme responsible for "activated L-serine sulphydrase" activity in nematodes. AB - The biochemical properties of the enzyme responsible for nematode "activated L serine sulphydrase" activity (L-cysteine + R-SH----cysteine thioether + H2S) have been investigated using primarily the gastro-intestinal nematodes Nippostrongylus brasiliensis and Haemonchus contortus. The activated L-serine sulphydrase enzyme was found to be cytosolic in origin and exhibited maximal activity at pH 9.0. Enzyme activity was widely distributed amongst the major tissues of adult female Ascaris suum but was particularly abundant in longitudinal muscle. The enzyme appeared to have a rigid specificity for L-cysteine as the primary thiol substrate, but was capable of utilising a number of sulphur amino acids (and derivatives) and nonphysiological thiols as second substrates. The best second thiol substrates were nonphysiological, hydroxyl-containing thiols that showed some structural similarity to the standard second substrate, 2-mercaptoethanol. Kinetic analyses revealed that the enzyme operates by a sequential catalytic mechanism, and the absolute Michaelis constants were: KL-cysteine = 0.21 +/- 0.02 mM and K2-mercaptoethanol = 5.58 +/- 0.59 mM. The enzyme was relatively insensitive to inhibition by a variety of substrate analogues and known inhibitors of pyridoxal 5'-phosphate dependent enzymes, whilst plant phenols caused significant levels of inhibition. The most potent inhibitors discovered were the anthelmintics bithionol, dichlorophene and hexachlorophene. Further characterisation revealed that hexachlorophene was a parabolic competitive inhibitor of the activated L-serine sulphydrase enzyme. PMID- 1740181 TI - Theileria annulata: alterations in phosphoprotein and protein kinase activity profiles of infected leukocytes of the bovine host, Bos taurus. AB - The phosphoprotein profiles of T. annulata-infected and uninfected leukocyte cell lines were compared by both in vivo and in vitro labeling assays. Three phosphoproteins were unique to T. annulata-infected cells, while a further two were quantitatively increased relative to uninfected cells. In addition, two proteins were present and phosphorylated only in the uninfected cell lines, suggesting either a repression of these proteins or their dephosphorylation upon infection of the host cell by the parasite. In order to determine if alterations in protein kinase activity may be responsible for these differences, as opposed to levels of available substrate, an in situ electrophoretic protein kinase assay was developed. This assay allowed a crude separation of protein kinases and revealed alterations in the protein kinase profile of Theileria-infected cells which reflected the differences observed in phosphoprotein profiles. Two protein kinases were unique to infected cells, a further two were more active in infected cells while one was more active in uninfected cells. PMID- 1740182 TI - Plasmodium fragile: cytoadherence of parasitized rhesus monkey erythrocytes to human endothelial cells under shear flow conditions. PMID- 1740183 TI - Molecular characterization of cDNA sequences encoding glutathione S-transferases of Fasciola hepatica. PMID- 1740184 TI - Proteases as biological regulators. Introductory remarks. PMID- 1740185 TI - Proteolysis in protein import and export: signal peptide processing in eu- and prokaryotes. AB - Numerous proteins in pro- and eukaryotes must cross cellular membranes in order to reach their site of function. Many of these proteins carry signal sequences that are removed by specific signal peptidases during, or shortly after, membrane transport. Signal peptidases have been identified in the rough endoplasmic reticulum, the matrix and inner membrane of mitochondria, the stroma and thylakoid membrane of chloroplasts, the bacterial plasma membrane and the thylakoid membrane of cyanobacteria. The composition of these peptidases varies between one and several subunits. No site-specific inhibitors are known for the majority of these enzymes. Accordingly, signal peptidases recognize structural motifs rather than linear amino acid sequences. Such motifs have become evident by employing extensive site-directed mutagenesis to investigate the anatomy of signal sequences. Analysis of the reaction specificities and the primary sequences of several signal peptidases suggests that the enzymes of the endoplasmic reticulum, the inner mitochondrial membrane and the thylakoid membrane of chloroplasts all have evolved from bacterial progenitors. PMID- 1740187 TI - Proteases and proteolysis in the lysosome. AB - Proteins sequestered by a non-selective bulk process within the lysosomes turn over with an apparent half-life of about 8 minutes and this rapid lysosomal proteolysis is initiated by endopeptidases, in particular by the cathepsins D and L. We describe also the cathepsins B and H which show mainly exopeptidase and only low endopeptidase activity. Especially cathepsin H is most probably the only lysosomal aminopeptidase in many cell types. Additionally, the properties of other mammalian lysosomal endo- and exopeptidases are compared. Finally, we discuss some of the conditions for the action of lysosomal proteases as the low intralysosomal pH, the high part of lysosomal thiol groups and the absence of intralysosomal proteinase inhibitors. PMID- 1740189 TI - Genetic analysis of ubiquitin-dependent protein degradation. AB - Selective degradation of cellular proteins serves to eliminate abnormal proteins and to mediate the turnover of certain short-lived proteins, many of which have regulatory functions. In eukaryotes a major pathway for selective protein degradation is ATP-dependent and is mediated by the ubiquitin system. This pathway involves substrate recognition by components of a ubiquitin-protein ligase system, covalent attachment of ubiquitin moieties to proteolytic substrates, and subsequent degradation of these conjugates by a multicatalytic protease complex. Recent genetic evidence suggests that the remarkable selectivity of this process is largely controlled at the level of substrate recognition by the ubiquitin ligase system. In Saccharomyces cerevisiae, ubiquitin-conjugating enzymes UBC1, UBC4 and UBC5 have been identified as key components of this highly conserved degradation pathway. Genetic analysis indicates that ubiquitin-dependent proteolysis is essential for cell viability and that UBC4 and UBC5 enzymes are essential components of the eukaryotic stress response. PMID- 1740186 TI - The early and late processing of lysosomal enzymes: proteolysis and compartmentation. AB - Lysosomal enzymes are subjected to a number of modifications including carbohydrate restructuring and proteolytic maturation. Some of these reactions support lysosomal targeting, others are necessary for activation or keeping the enzyme inactive before being segregated, while still others may be adventitious. The non-segregated fraction of the enzyme is secreted and can be isolated from the medium. It is considered that the secreted lysosomal enzymes fulfill certain physiological and pathophysiological roles. By comparing the secreted and the intracellular enzymes it is possible to distinguish between the reactions that occur before and after the segregation. In this review the reactions that may influence the segregation are referred to as the early processing and those characteristic for the enzymes isolated from lysosomal compartments as the late processing. The early processing is characterized mainly by modifications of carbohydrate side chains. In the late processing, proteolytic fragmentation represents the most conspicuous changes. The review focuses on the compartmentation of the reactions and the proteolytic fragmentation of lysosomal enzyme precursors. While a plethora of proteolytic reactions are involved, our knowledge of the proteinases responsible for the particular maturation reactions remains very limited. The review points also to work with cells from patients affected with lysosomal storage disorders, which contributed to our understanding of the lysosomal apparatus. PMID- 1740188 TI - Autophagy and other vacuolar protein degradation mechanisms. AB - Autophagic degradation of cytoplasm (including protein, RNA etc.) is a non selective bulk process, as indicated by ultrastructural evidence and by the similarity in autophagic sequestration rates of various cytosolic enzymes with different half-lives. The initial autophagic sequestration step, performed by a poorly-characterized organelle called a phagophore, is subject to feedback inhibition by purines and amino acids, the effect of the latter being potentiated by insulin and antagonized by glucagon. Epinephrine and other adrenergic agonists inhibit autophagic sequestration through a prazosin-sensitive alpha 1-adrenergic mechanism. The sequestration is also inhibited by cAMP and by protein phosphorylation as indicated by the effects of cyclic nucleotide analogues, phosphodiesterase inhibitors and okadaic acid. Asparagine specifically inhibits autophagic-lysosomal fusion without having any significant effects on autophagic sequestration, on intralysosomal degradation or on the endocytic pathway. Autophaged material that accumulates in prelysosomal vacuoles in the presence of asparagine is accessible to endocytosed enzymes, revealing the existence of an amphifunctional organelle, the amphisome. Evidence from several cell types suggests that endocytosis may be coupled to autophagy to a variable extent, and that the amphisome may play a central role as a collecting station for material destined for lysosomal degradation. Protein degradation can also take place in a 'salvage compartment' closely associated with the endoplasmic reticulum (ER). In this compartment unassembled protein chains are degraded by uncharacterized proteinases, while resident proteins return to the ER and assembled secretory and membrane proteins proceed through the Golgi apparatus. In the trans-Golgi network some proteins are proteolytically processed by Ca(2+)-dependent proteinases; furthermore, this compartment sorts proteins to lysosomes, various membrane domains, endosomes or secretory vesicles/granules. Processing of both endogenous and exogenous proteins can occur in endosomes, which may play a particularly important role in antigen processing and presentation. Proteins in endosomes or secretory compartments can either be exocytosed, or channeled to lysosomes for degradation. The switch mechanisms which decide between these options are subject to bioregulation by external agents (hormones and growth factors), and may play an important role in the control of protein uptake and secretion. PMID- 1740193 TI - Progestins, breast cancer, and the limitations of epidemiology. PMID- 1740192 TI - Progestins and breast cancer: an epidemiologic review. AB - OBJECTIVE: To provide a worldwide review of all studies that have examined the relationship between progestins, as contained in both contraceptive and postmenopausal replacement therapies, and breast cancer risk. An overview of utilization patterns for progestins, as well as a review of possible biological mechanisms for progestins' action on breast tissue, are also presented. DATA IDENTIFICATION: All major epidemiologic studies conducted since 1980 have been identified through MEDLINE searches through the published literature and personal communications with prominent researchers in the area. STUDY SELECTION: Only studies that specifically examined the effects of progestin use are discussed here; these include investigations of progestins, in combination or singularly, as the main hypothesis or a subgroup analysis. RESULTS: The majority of studies have examined combination estrogen and progestin products (oral contraceptives), and subgroup analyses of progestins have been impeded by low statistical power and the fact that each progestin possesses different types of pharmacological activity. Only a few studies of long-acting injectable progestins exist, confirming a general lack of specific information on the progesterone-breast cancer relationship. Investigations of the effect on breast cancer of the addition of progestins to postmenopausal replacement therapy have also produced inconsistent results. CONCLUSIONS: To date, there is no consistent evidence of an association between progestins and breast cancer. There is need for further study, particularly of patients in potentially high-risk groups, including those with (1) extended hormone exposure before age 25 and/or first full term pregnancy and (2) exposure in the postmenopausal period. PMID- 1740190 TI - Proteases and protein degradation in Escherichia coli. AB - In E. coli, protein degradation plays important roles in regulating the levels of specific proteins and in eliminating damaged or abnormal proteins. E. coli possess a very large number of proteolytic enzymes distributed in the cytoplasm, the inner membrane, and the periplasm, but, with few exceptions, the physiological functions of these proteases are not known. More than 90% of the protein degradation occurring in the cytoplasm is energy-dependent, but the activities of most E. coli proteases in vitro are not energy-dependent. Two ATP dependent proteases, Lon and Clp, are responsible for 70-80% of the energy dependent degradation of proteins in vivo. In vitro studies with Lon and Clp indicate that both proteases directly interact with substrates for degradation. ATP functions as an allosteric effector promoting an active conformation of the proteases, and ATP hydrolysis is required for rapid catalytic turnover of peptide bond cleavage in proteins. Lon and Clp show virtually no homology at the amino acid level, and thus it appears that at least two families of ATP-dependent proteases have evolved independently. PMID- 1740194 TI - Cytokine levels in follicular fluid of polycystic ovaries in patients treated with dexamethasone. AB - OBJECTIVE: To assess the levels of cytokines in the follicular fluid of stimulated ovaries. DESIGN: The study included two groups of four patients with polycystic ovarian disease. These were diagnosed by clinical and ultrasonic features and characteristic hormonal profiles, treated with gonadotropin releasing hormone-analogue and human menopausal gonadotropin. One group received dexamethasone (DEX). MAIN OUTCOME: Dexamethasone is capable of directly affecting granulosa and immune cells. It was also expected to affect cytokine production of granulosa and immune cells of the ovary. RESULTS: This study demonstrates that FF from patients treated with DEX has reduced tumor necrosis factor (TNF) activity and elevated colony-stimulating factor levels. Regardless of the treatment with DEX, the follicles with high levels of TNF contained minimal concentrations of estradiol. Interleukin-6 did not differ between the FF samples. CONCLUSIONS: These results suggest a role for cytokines in the process of folliculogenesis and ovarian maturation. Modification of cytokines by DEX might explain the beneficial effect of fertility. PMID- 1740191 TI - The role of proteolytic processing in the morphogenesis of virus particles. AB - Proteinases are encoded by many RNA viruses, all retroviruses and several DNA viruses. They play essential roles at various stages in viral replication, including the coordinated assembly and maturation of virions. Most of these enzymes belong to one of three (Ser, Cys or Asp) of the four major classes of proteinases, and have highly substrate-selective and cleavage specific activities. They can be thought of as playing one of two general roles in viral morphogenesis. Structural proteins are encoded by retroviruses and many RNA viruses as part of large polyproteins. Their proteolytic release is a prerequisite to particle assembly; consequent structural rearrangement of the capsid domains serves to regulate and direct association and assembly of capsid subunits. The second general role of proteolysis is in assembly-dependent maturation of virus particles, which is accompanied by the acquisition of infectivity. PMID- 1740195 TI - Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. AB - OBJECTIVE: To determine if the hormonal imbalance in women with polycystic ovary syndrome (PCOS) continues into and after menopause and to analyze factors constituting an increased risk for developing metabolic disorders. DESIGN: The study was a transectional retrospective cohort follow-up of patients with PCOS. SETTING: The women with PCOS were recruited from hospital clinics, and referents were randomized from a population study of women. PARTICIPANTS: Thirty-three women ages 40 to 59 years with ovarian histopathology typical of PCOS at wedge resection 22 to 31 years previously; 132 age-matched referents were analyzed. MAIN OUTCOME MEASURES: Clinical data were collected via a questionnaire supplemented with an interview in connection to a clinical examination that also included fasting venous sampling. RESULTS: Infertility, hirsutism, and oligomenorrhea were more common among the subjects with PCOS, but there was a considerable spontaneous restitution of cyclic regularity with time. Women with PCOS were more often hysterectomized and entered menopause later compared with referents. The hormone data show a typical profile for PCOS. Compared with referents women with PCOS showed marked increase in prevalence of central obesity, higher basal serum insulin concentrations, and a higher prevalence of diabetes mellitus and hypertension. CONCLUSION: Perimenopausal women with PCOS have an increased morbidity in hypertension and diabetes mellitus that adds to the classic symptoms, such as anovulation, hirsutism, and infertility. PMID- 1740196 TI - CA-125 levels in human uterine fluid. AB - OBJECTIVE: To measure uterine fluid CA-125 concentration and to determine if any menstrual cycle phase dependent changes exist in its level. Serum levels are measured for comparison. DESIGN: CA-125 levels in uterine fluid were measured during the follicular and luteal phases of the menstrual cycle. In a sequential study, paired uterine fluid and serum samples were obtained once in both midfollicular and midluteal phases of the same menstrual cycle. RESULTS: CA-125 in uterine fluid during the follicular phase (n = 14) ranged from 16.4 x 10(3) to 616.5 x 10(3) U/mL, and from 6.2 x 10(3) to 567.3 x 10(3) U/mL in the luteal phase (n = 11). In the paired sequential uterine fluid and serum samples, (1) the means (+/- SEM) CA-125 in uterine fluid were 81.5 x 10(3) +/- 37.9 x 10(3) U/mL and 91.4 x 10(3) +/- 56.8 x 10(3) U/mL in the midfollicular and midluteal phases, respectively (P = 0.75); (2) the CA-125 levels in serum increased in the midluteal phase (P less than 0.05); and (3) compared with serum, uterine fluid levels were greater with a wider range. CONCLUSIONS: When compared with serum CA 125, uterine fluid contains high concentrations varying over a wide range without fluctuation between the follicular and luteal phases of the menstrual cycle. PMID- 1740197 TI - Hysterosalpingography and selective salpingography in the differential diagnosis of chemical intrauterine versus tubal pregnancy. AB - OBJECTIVE: To determine the validity of hystersalpingography (HSG) and/or bilateral selective salpingography in the differential diagnosis of early (biochemical) intrauterine versus intratubal abortions. DESIGN: The study design involved the performance of HSG and selective salpingography in sequential patients with low declining beta-human chorionic gonadotropin (beta-hCG) values. SETTING: Medical School-affiliated Infertility Center. PARTICIPANTS: Four sequential pregnant infertility patients who demonstrated declining beta-hCG levels before pregnancy could be confirmed by ultrasound (chemical pregnancies). RESULTS: Three of four patients demonstrated a characteristic tubal opacification pattern in conjunction with a normally appearing endometrial cavity, considered diagnostic of an early tubal pregnancy. In contrast, a missed intrauterine pregnancy (IUP) demonstrated a characteristically abnormal endometrial cavity. CONCLUSIONS: Some early (chemical) pregnancy losses are intratubal rather than intrauterine. The correct differential diagnosis of early missed IUPs versus intratubal pregnancies is important because of its prognostic significance. PMID- 1740198 TI - Intrauterine insemination outperforms intracervical insemination in a randomized, controlled study with frozen, donor semen. AB - OBJECTIVE: To assess the efficacy of intrauterine insemination (IUI) in a donor insemination program. DESIGN: Prospective randomized clinical trial. SETTING: Donor insemination program. PATIENTS, PARTICIPANTS: Women undergoing insemination were randomly assigned to receive either IUI or intracervical insemination for a maximum of six cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Cycle fecundity rates between the two routes were compared. RESULTS: The monthly fecundity rate for intracervical insemination was 5.1% compared with 23% by IUI. By life table analysis, pregnancy rates for IUI were significantly higher than intracervical insemination (P = 0.02). CONCLUSIONS: Intrauterine insemination with quarantined donor sperm is superior to intracervical insemination. PMID- 1740199 TI - An epidemiologic study of smoking and primary infertility in women. AB - OBJECTIVE: To determine the relationship between cigarette smoking and primary female infertility. DESIGN: Retrospective, case-control study. SETTING: Population-based and randomly selected from eight geographic areas in the United States. PARTICIPANTS: Women, 20 to 54 years of age, who were randomly selected to serve as the control group of the Cancer and Steroid Hormone Study were used for this study. Within this group, there were 483 women who were classified as having experienced primary infertility and 2,231 women eligible to serve as controls. Primary infertility, defined as 24 consecutive months of unprotected intercourse without conception, was documented from a calendar of each women's reproductive and contraceptive history. RESULTS: Smoking one pack of cigarettes per day (odds ratio = 1.36) and starting to smoke before 18 years of age (odds ratio = 1.30) were significantly associated with increased risk of infertility. Life table and proportional hazards analysis indicated that smoking did not significantly increase the time required to conceive among infertile women. CONCLUSIONS: Number of cigarettes smoked and age when the women began smoking contributed to infertility in this study. It is reasonable, therefore, to recommend that women stop smoking when they are attempting to become pregnant. PMID- 1740200 TI - Cyclic changes in the concentration of glucose and fructose in human cervical mucus. AB - OBJECTIVE: To determine a possible cyclic change in the concentration of glucose and fructose in the aqueous phase of human cervical mucus (CM). DESIGN: Concentrations of glucose and fructose were longitudinally determined in the aqueous phase of CM of normal cycling women using enzymatic techniques, modified for small quantities. SETTING: Patients visiting a fertility clinic were selected. PATIENTS: Nine healthy women with regular menstrual cycles of 28 +/- 3 days that appeared to be ovulatory, demonstrated by sonographic follicle immaging and serum progesterone (P) measurements. INTERVENTIONS: Cervical mucus samples were longitudinally collected preovulatory, postovulatory, and premenstrual in ovulatory cycles, monitored by ultrasound and blood estradiol and P measurements. MAIN OUTCOME MEASURES: The study was designed to measure glucose and fructose longitudinally on three different points during one cycle. RESULTS: The preovulatory glucose concentrations in CM were lower than postovulatory and premenstrual. The preovulatory fructose concentrations were lower than premenstrual. The glucose concentration correlated with the blood P level. CONCLUSION: There is a consistent change in the glucose concentration measured in human CM in three phases of the menstrual cycle. The preovulatory and premenstrual fructose concentrations differ significantly. Knowledge of the carbohydrate metabolism in human cervical mucus may contribute in illuminating the possible role of the carbohydrate metabolism in sperm migration at midcycle and implantation in the luteal phase. PMID- 1740201 TI - Chlamydial antibodies and deoxyribonucleic acid in patients with ectopic pregnancy. AB - OBJECTIVE: To evaluate the importance of previous and persisting chlamydial infection for ectopic pregnancy (EP). DESIGN: A prospective study of women with EP. SETTING: Hospitalized patients. PATIENTS AND CONTROLS: Eighty-six women with EP with (group I; n = 35) or without (group II; n = 51) risk factors for EP and chlamydial infection. Age-matched normally pregnant women served as controls. INTERVENTIONS: Blood samples were drawn from patients and controls for antibody determination. MAIN OUTCOME MEASURES: The frequency of immunoglobulin G antibodies was compared between patients and controls, and the polymerase chain reaction (PCR) was used to detect chlamydial deoxyribonucleic acid (DNA) in tubal tissue from 33 patients (70 specimens). RESULTS: Immunoglobulin G antibodies (titer greater than or equal to 32) were significantly more common among patients than in controls (51% versus 31%, P less than 0.025). The difference was more pronounced between group I and controls (69% versus 31%, P less than 0.005). Chlamydial DNA was not detected in any tubal specimen. CONCLUSIONS: An association was found between previous chlamydial infection (serologically) and EP, especially in women with risk factors, but no evidence of persisting chlamydial infection in the tubes could be demonstrated using PCR. PMID- 1740202 TI - Psychological aspects of donor insemination: evaluation and follow-up of recipient couples. AB - OBJECTIVE: To evaluate the utility of psychological screening for couples entering a donor insemination program. DESIGN: Each spouse completed questionnaires. A psychologist reviewed them and rated the psychological fitness of the couple for participation in the program. Follow-up questionnaires were sent to each couple at a mean of 11 months after entry into the program. SETTING: Applicants for donor insemination were studied in an infertility program in a large, tertiary referral center. PATIENTS, PARTICIPANTS: Consecutive applicants to enter the donor insemination program were required to participate in the initial evaluation. INTERVENTIONS: Couples judged by the psychologist to be at risk for a poor psychological outcome had an assessment and counseling interview with the psychologist before proceeding with insemination. MAIN OUTCOME MEASURES: Initially, the Stress and Infertility Questionnaire measured specific anxieties related to donor insemination, marital and sexual impact, and attitudes about confidentiality; the Brief Symptom Inventory measured psychological distress; and the Dyadic Adjustment Inventory assessed marital satisfaction. At follow-up, 48% of couples returned a modified version of the Stress and Infertility Questionnaire and the other two questionnaires. RESULTS: The psychologist's rating was predictive of pregnancy rates (59% for excellent candidates, 41% for acceptable couples, and 14% for couples psychologically at risk). At-risk couples were more likely to drop out of the program (50% versus only 20% of other couples). Sexual problems were reported by 59% of women and 53% of men. Couples believed that a child should not be told of the donor insemination (74% of wives and 80% of husbands). Initially, 64% of wives and 70% of husbands chose total secrecy with families or friends, and these attitudes shifted little over time. CONCLUSION: This screening procedure is cost-effective and suggests that psychological intervention should be attempted with at-risk couples. PMID- 1740203 TI - Utility of zona pellucida drilling in cases of severe semen alterations in man. AB - OBJECTIVE: To evaluate the utility of zona drilling for human severe sperm alterations in in vitro fertilization (IVF). DESIGN: A prospective randomized study was conducted according to random assignment of collected oocytes to a control or zona drilling procedure. SETTING: Reproductive Biology Laboratory, University Hospital of Nantes, France. PATIENTS: Twenty infertile couples with severe semen defects and previous IVF failure. INTERVENTIONS: Ultrasound-guided transvaginal follicular aspiration. RESULTS: Fertilization rates were compared to assess the advantages of zona drilling: 93% (80/86) drilled oocytes survived and 18.75% (15) were fertilized, whereas only 3% (3/100) control oocytes were fertilized. The polyspermy rate for fertilized drilled oocytes was high (10/15; 66.6%). The normal fertilization rate after zona drilling remained very low (5/86; 5.8%) and was not statistically different from that of control oocytes (3/100; 3%). One implantation occurred after replacement of five drilled embryos in three patients but resulted in early miscarriage. Replacement of the single control embryo led to a progressive pregnancy and normal male birth. CONCLUSIONS: This study indicates that zona drilling does not improve IVF results in cases of severe semen alterations. PMID- 1740204 TI - The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer. AB - OBJECTIVE: To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies. DESIGN AND PATIENTS: Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6 month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score. SETTING: All patients were treated in our IVF Unit. MAIN OUTCOME MEASURE: Clinical pregnancy was used as our main outcome measure of success. RESULTS: A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001). CONCLUSIONS: It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis. PMID- 1740205 TI - Leuprolide acetate-prepared in vitro fertilization-gamete intrafallopian transfer cycles: efficacy versus controls and cost analysis. AB - OBJECTIVE: To evaluate the effect of gonadotropin-releasing hormone agonist (GnRH a) when given through stimulation with gonadotropins versus stopping it as stimulation was initiated versus a control group unprepared in this manner. Also, to construct a cost analysis for this type of therapy in an in vitro fertilization-gamete intrafallopian transfer program (IVF-GIFT). DESIGN: Prospective, consecutive, randomized, with a control group. SETTING: An out patient IVF-GIFT program. PATIENTS: One hundred new patients entering an IVF-GIFT program. INTERVENTIONS: In vitro fertilization or GIFT cycles with or without preparation (pituitary suppression) by GnRH-a administration in which suppression was continued or halted as gonadotropins were begun. MAIN OUTCOME MEASURES: Cancellation rates, ampules, and days of gonadotropin use, costs, estradiol (E2) level, egg numbers and quality, and pregnancy rates. RESULTS: Stopping GnRH-a (leuprolide acetate) therapy as stimulation was begun did not lessen the suppressive effect in reduction of spontaneous luteinizing hormone surge as seen with continued use of agonist. In contrast, the control group had a 30.3% cancellation rate before ovum retrieval. The E2 and egg data among the groups were similar, but as expected, agonist use led to the need for more and longer duration of gonadotropin stimulation. Pregnancy rates were not different by group. Costs were approximately even by the third initiated cycle. PMID- 1740206 TI - After superovulation-intrauterine insemination fails: the prognosis for treatment by gamete intrafallopian transfer/pronuclear stage transfer. AB - OBJECTIVE: To determine the prognosis for gamete intrafallopian transfer (GIFT)/pronuclear stage transfer (PROST) treatment after prior superovulation intrauterine insemination (IUI). DESIGN: Matched, retrospective. SETTING: Outpatient university endocrine-infertility program. PATIENTS, PARTICIPANTS: One hundred forty-four women matched for infertility factors and age were studied according to the following three treatment groups: superovulation-IUI only, GIFT/PROST only, or GIFT/PROST after superovulation-IUI. MAIN OUTCOME MEASURES: Per cycle and cumulative pregnancy rates (PRs) were compared utilizing life table analysis. RESULTS: Cumulative PRs (0.408) for superovulation-IUI only were lower than initial (0.469) and cumulative (0.802) cycle fecundity of GIFT/PROST (P = 0.002). Per cycle and cumulative PRs did not differ between GIFT/PROST only versus GIFT/PROST after superovulation-IUI. CONCLUSIONS: Gamete intrafallopian transfer/PROST may be cost-effective when compared with superovulation-IUI. The prognosis for GIFT/PROST success is not negatively affected by earlier superovulation-IUI treatment failure. PMID- 1740207 TI - Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles. AB - OBJECTIVE: To determine characteristics associated with pregnancy and multiple gestation after clomiphene citrate (CC)-intrauterine insemination (IUI). DESIGN: Prospective study of all patients undergoing CC-IUI between January 1, 1983 and December 31, 1989. SETTING: Private fertility clinic. PATIENTS: Eight hundred forty-nine patients undergoing 1,974 cycles of CC-IUI. MAIN OUTCOME MEASURES: Relationship between number and size of preovulatory follicles, age, additional infertility diagnosis, medication, and initial semen quality to fecundity, birth, and multiple gestation. RESULTS: Uncorrected, per cycle fecundity was 7.2%. The number of follicles greater than or equal to 12 mm (r = 0.055, P less than 0.05) was and the number greater than or equal to 15, 18, and 21 mm was not correlated with fecundity. Endometriosis with (P = 0.013) or without (P less than 0.0005) tubal adhesions and tubal adhesions alone (P = 0.005), decreased fecundability by 50%. Initial semen quality did not affect fecundity, unless semen concentration was less than 5 x 10(6)/mL or motility was less than 20%. Multiple pregnancy was not associated with the dose of CC, use of human chorionic gonadotropin, or number of follicles. CONCLUSIONS: Multiple pregnancy was unrelated to follicle numbers or to CC dose. The highest birth rates after CC-IUI occurred when initial sperm concentration was greater than or equal to 5 x 10(6)/mL, motility was greater than or equal to 20%, and no endometriosis or adhesions were present. PMID- 1740208 TI - Performance of cryopreserved pre-embryos obtained in in vitro fertilization cycles with or without a gonadotropin-releasing hormone agonist. AB - OBJECTIVE: To evaluate the viability and potential for pregnancy of cryopreserved/thawed pre-embryos obtained after ovarian stimulation using gonadotropin-releasing hormone agonist (GnRH-a) adjunct therapy. DESIGN: Retrospective clinical evaluation of all patients receiving a gonadotropin ovarian stimulation protocol (follicle-stimulating hormone/human menopausal gonadotropin [FSH/hMG]) with/without GnRH-a. SETTING: Academic tertiary clinical care unit. PATIENTS: Patients receiving leuprolide acetate (LA)/FSH/hMG (n = 136: LA in the luteal phase; long protocol) were compared with patients receiving FSH/hMG alone (n = 130) within the same time-frame in our program (April 1987 through October 1989). INTERVENTIONS: All patients had both a cycle in which pre embryos were transferred fresh and a cycle of thaw of cryopreserved pre-embryos (frozen at the pronuclear stage in a slow freeze-thaw protocol using 1,2 propanediol) transferred in monitored natural cycles. MAIN OUTCOME MEASURES: Groups were similar in age, etiology of infertility, and cycle day 3 serum FSH levels; a significantly higher (P less than 0.001) number of preovulatory oocytes was recovered in the GnRH-a group. Both groups of patients were transferred an equal number of pre-embryos at the time of IVF. Cycles with frozen/thawed pre embryos were evaluated based on the analysis of the three main variables that demonstrate cryopreservation efficiency: survival rate, implantation rate, and term pregnancy rate (PR). RESULTS: Non-GnRH-a group (113 transfers): pre-embryo survival, 71.5%; PR/transfer, 24.7%; implantation rate, 16.0%; GnRH-a group (125 transfers): pre-embryo survival 71.6%; PR/transfer, 32.8%; implantation rate, 12.0% (no significant differences). CONCLUSIONS: The use of GnRH-a produced pre embryos of equal aptitude for development after cryopreservation at the pronuclear stage when compared with a similar gonadotropin stimulation treatment without GnRH-a. PMID- 1740209 TI - The relationship between embryo quality and the occurrence of multiple pregnancies. AB - OBJECTIVE: To study the relationship between the quality of the transferred embryos and the occurrence of multiple pregnancies. Embryo quality was defined by the cleavage rate and by morphological parameters such as blastomere size and the presence or absence of anucleate fragments. DESIGN: A retrospective analysis of 1,915 consecutive transfers of fresh embryos between January 1986 and December 1989. SETTING: All the embryo transfers (ETs) were performed in patients from the in vitro fertilization program of the Center for Reproductive Medicine, Vrije Universiteit Brussel, Brussels, Belgium. RESULTS: We confirmed the relationship between the number of embryos transferred and the pregnancy rate (PR): 11.9% of the single, 19.0% of the double, and 34.1% of the triple ETs were successful. Thirty-one percent of these triple embryo replacements resulted in a multiple gestation. At the time of transfer (44 to 48 hours after insemination), we observed that embryos that had undergone at least two mitotic divisions implanted better than two-cell embryos of comparable morphological appearance (implantation rate per transferred embryo: 21.3% versus 12.3%, P less than 0.001) and that heavily fragmented embryos did not implant as well as embryos without or with fewer anucleate fragments (1.5% versus 14.1%, P less than 0.001). The PR, implantation rate, and the incidence of multiple pregnancies increased significantly with the number of good quality embryos that were transferred. CONCLUSIONS: Our study indicated that embryo quality based on morphological observations could predict the occurrence of multiple pregnancies. PMID- 1740210 TI - Discordant secretion of pregnancy specific beta 1-glycoprotein and human chorionic gonadotropin by human pre-embryos cultured in vitro. AB - OBJECTIVE: To study and compare the secretion of pregnancy specific beta 1 glycoprotein (SP1) and human chorionic gonadotropin (hCG) by human pre-embryos, cultured in vitro, with their respective morphological development. DESIGN: Spare human pre-embryos from randomly selected women participating in a program of in vitro fertilization (IVF) were studied prospectively. SETTING: Pre-embryos were cultured, and hormone release was determined in academic research laboratories. PATIENTS, PARTICIPANTS: Pre-embryos (n = 108) cultured for 14 days after fertilization in Ham's F-10 medium (GIBCO Ltd., Paisley, Scotland) were observed, and hCG and SP1 were measured in the culture media at regular intervals. MAIN OUTCOME MEASURES: Discordant secretion of SP1 and hCG. RESULTS: Of the 98 bipronucleate pre-embryos, 53.6% formed blastocysts, 17.3% of which hatched. Human chorionic gonadotropin was detected from day 7 after fertilization concomitantly with blastocyst formation, thereafter showing a logarithmic increase (maximum 10,650 mIU) until the first signs of embryonic disintegration. Pregnancy-specific beta 1-glycoprotein release started 3 to 4 days after fertilization independently of the morphological development and the future production of hCG, thereafter displaying a nonlogarithmic increase (maximum 41 ng). CONCLUSIONS: Hormone secretion and morphological development are unique for each pre-embryo. Human chorionic gonadotropin and SP1 seem to have different biochemical and physiological regulation. PMID- 1740211 TI - Immunosuppressive activity and alpha interferon concentrations in human embryo culture media as an index of potential for successful implantation. AB - OBJECTIVE: To evaluate potential correlations between establishment of pregnancy and immunosuppressive activity secreted by the preimplantation embryo. DESIGN: To evaluate immunosuppressive activity, supernatants from preimplantation embryos were assessed for their ability to inhibit lymphocyte proliferation. Additionally, alpha interferon concentrations were also measured in these supernatants. We compared these parameters from embryo culture supernatants of women who did and did not achieve pregnancy after in vitro fertilization (IVF). Immunosuppression was assessed using a lymphocyte proliferation assay with concanavalin A (Con A) and phytohemagglutinin (PHA) as mitogens. SETTING: In vitro fertilization program at the University of Utah Medical Center. PARTICIPANTS: Couples less than 40 years of age, with normal semen quality and bilateral tubal obstruction. RESULTS: Immunosuppression calculated using the stimulation index (mean +/- SEM) in pregnant and nonpregnant women, respectively, were: Con A: 43.9 +/- 3.9 versus 19.1 +/- 10.1, P less than 0.04. PHA: 23.6 +/- 5.6 versus 12.5 +/- 12.8, P less than 0.02. Alpha interferon levels (mean +/- SD) in pregnant and nonpregnant women were not significantly different: 23.98 +/- 9.6 U/mL versus 24.79 +/- 2.5 U/mL. CONCLUSIONS: We conclude that pre-embryos with the capacity for successful implantation secrete greater amounts of immunosuppressive factors than those destined not to implant, as measured by Con A and PHA lymphocyte proliferation assays. Refinement of assay techniques and identification of the substances involved could have significant impact on IVF programs. PMID- 1740212 TI - An improved medium for long-term culture of human embryos overcomes the in vitro developmental block and increases blastocyst formation. AB - OBJECTIVE: To determine if a culture medium, designated CZB after the authors who first described it, which is supplemented with 0.11 mM ethylenediaminetetraacetic acid, 1.0 mM glutamine, 31.30 mM lactate, and 0.27 mM pyruvate and is lacking glucose for the initial stages of culture that overcomes the in vitro two-cell block of mouse embryos, can improve the rate of blastocyst formation of human embryos in long-term cultures and increase the pregnancy rate (PR) when used in a clinical in vitro fertilization (IVF) program. DESIGN: The study is in two parts. Initially, excess oocytes from IVF and gamete intrafallopian transfer patients were fertilized in vitro and then placed in long-term culture of either CZB plus 10% heat-inactivated human serum (32 zygotes) or Earle's balanced salt solution (EBSS) supplemented with 0.45 mM pyruvate plus 10% human serum (28 zygotes) to determine if CZB medium could enhance in vitro development and increase blastocyst formation when compared with EBSS. Subsequently, CZB or EBSS medium was used for short-term cultures of embryos in a clinical IVF program to determine if the use of CZB could increase the clinical IVF PR. SETTING: Private practice of one author (M.D.). PATIENTS: The excess oocytes were donated by couples not wishing to have cryopreservation. In the clinical trial, 49 couples presenting with tubal or male factor infertility and who had three or more fertilized zygotes were randomly assigned to one of the culture media being used. RESULTS: In long-term cultures, embryos were observed at 42, 66, 90, 114, and 138 hours after fertilization and scored for blastomere number, degree of fragmentation, and developmental arrest. When CZB- and EBSS-cultured embryos were evaluated over 138 hours, there was a significant increase in the number of CZB cultured embryos reaching the blastocyst stage (56% versus 20%; P less than 0.009) and less fragmentation of CZB-cultured embryos (18.8% versus 50%; P less than 0.01). In short-term cultures, pronuclear stage embryos from patients undergoing IVF were cultured in CZB or EBSS for 24 hours, graded, and then used in embryo transfers. Of the 28 patients assigned to EBSS, 6 became pregnant (21.4%), and of the 21 assigned to CZB, 5 attained pregnancy (23.8%). These results were not significantly different. CONCLUSIONS: The use of CZB for the long-term culture of human embryos is highly beneficial and increases the rate of blastocyst formation, but its use in an IVF program does not increase the clinical PR. PMID- 1740213 TI - Accuracy and precision of computer-aided sperm analysis in multicenter studies. AB - STUDY OBJECTIVES: To develop methods of instrument calibration and standardization that enable the use of computer-aided sperm analysis (CASA) technology in multicenter studies of sperm motility. SETTING: Clinical semen evaluation for the andrology laboratory and in vitro fertilization programs. PATIENTS: Semen specimens were selected from the videotape archives of the University of California at Davis Andrology Laboratory and used to produce a videotape reference standard for CASA instrument testing and calibration. Four identical CASA instruments, two each at two sites, were used to analyze the videotape. Machine accuracy was verified by manual analysis of the videotape. RESULTS: The coefficient of variation (CV) for repeated measures was between 1% and 8% for each variable on all CASA instruments. Mean values for CASA parameters varied as a function of the digitization threshold. A minimum CV was obtained at a particular threshold setting, suggesting an optimum for each machine. Because of high within-machine precision, slight differences in mean values between machines were statistically significant for some variables and some specimens; such differences are probably not biologically significant. CONCLUSION: Multicenter standardization of CASA instrumentation is possible, but threshold settings are one source of variation that must be controlled using CVs or another means of objective calibration. One method is to adjust the threshold of each instrument until the count obtained by CASA equals the count obtained by the manual method used to determine the dilution requirements for neat semen. PMID- 1740214 TI - Effect of volumetric mixtures of peritoneal and follicular fluid from the same woman on sperm motility and acrosomal reactivity in vitro. AB - OBJECTIVE: To study the effect of peritoneal (PF) and follicular fluids (FF from the same woman) as well as of given volumetric combinations thereof on sperm motility and acrosomal reactivity. DESIGN: Prospective. Peritoneal fluid and FF were incubated separately or in given volumetric combinations (PF/FF = 100/0, 75/25, 50/50, 25/75, 0/100; vol/vol) with swim-up sperm suspensions. SETTING: In vitro fertilization and general infertility clinic and laboratories. PATIENTS, PARTICIPANTS: Women participants of the gamete intrafallopian transfer program (motility study, n = 20; acrosomal reaction study, n = 14). Sperm donors of the artificial insemination program and men with given sperm parameters. INTERVENTIONS: Hormonal stimulation. Laparoscopy. MAIN OUTCOME MEASURES: Progressive velocity and percentage of motile gametes measured with multiple exposure photography. Acrosomal reactivity measured by an immunofluorescent technique. RESULTS: Follicular fluid always influenced progressive motility and also sustained the number of motile gametes, as function of time, better than PF or the PF/FF mixtures (P less than 0.05). The acrosomal reactivity of sperm incubated in the various PF/FF combinations was low; after 5 hours only the FF sperm suspensions showed a significant enhancement of acrosomally reacted gametes. CONCLUSION: At ovulation, FF transmit positive (motility- and acrosomal reactivity-enhancing) signals to sperm, whereas PF may transmit positive, neutral, or negative signals (noise signals). The volumetric combination of FF and PF in the tubal environment, which may differ from cycle to cycle and from woman to woman, could therefore result in synergic (or antagonistic) effects on the sperm fertility potential. PMID- 1740215 TI - The axonemal ultrastructure of spermatozoa from men with asthenospermia. AB - OBJECTIVE: To determine with the use of transmission electron microscopy (TEM) the proportion of patients with the semen pattern of severe asthenospermia (less than 20% motility) that have an abnormality of sperm axonemal structure as the basis for this disorder. DESIGN: Transverse sections of sperm tail axonemes were quantitatively analyzed, and the mean frequency per axoneme of the doublet microtubules, central pair, outer dynein arms, inner dynein arms, and radial spokes were determined. SETTING: Patients were being investigated for male infertility at the Reproductive Medicine Clinic at Monash Medical Centre (Melbourne). Semen samples were processed for and analyzed by TEM in the university laboratory. PATIENTS: Ten asthenospermic patients in whom repeated semen analysis demonstrated a percentage of sperm motility less than 20% were selected. MAIN OUTCOME MEASURE(S): The main measure was the quantitative analysis of sperm axonemes. The hypothesis that a reduction of axonemal components causes lowered motility derived from the results. RESULTS: Individual asthenospermic patients demonstrated significant reductions in at least three axonemal structures when compared with the normal mean. Statistical analysis of the grouped data showed that all axonemal components were significantly lower than the normal mean. CONCLUSIONS: The consistent reduction of axonemal components strongly suggests that axonemal deficiencies are the cause of lowered motility in asthenospermic patients. PMID- 1740216 TI - Chronic suppression of testicular function by constant infusion of gonadotropin releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata). AB - OBJECTIVE: To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). ANIMALS: Proven fertile male monkeys exhibiting normal testicular function. PROTOCOL: Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. RESULTS: (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. CONCLUSION: Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T. PMID- 1740217 TI - An intact zona pellucida is not necessary for successful mouse embryo cryopreservation. AB - OBJECTIVE: To determine the developmental potential of mouse embryos that underwent cryopreservation after micromanipulation of the zona pellucida. DESIGN: Gaps were produced in the zona pellucida of mouse oocytes or two-cell embryos by zona drilling with acid Tyrode's solution. Zona-drilled oocytes were fertilized in vitro and cultured to the two-cell stage. Two-cell embryos were frozen, thawed, and cultured to the expanded blastocyst stage. RESULTS: There was no difference in the rate of embryo survival post-thaw (248/318, 77% versus 288/345, 83.4%), or in the rate of development to the expanded blastocyst stage (91/248, 36.7% versus 88/288, 30.6%), between embryos that were zona drilled as oocytes and unmanipulated controls. Similarly, there was no difference in the rate of cryosurvival (206/217, 94.9% versus 168/187, 89.8%) or development to the blastocyst stage (154/206, 74.7% versus 132/168, 78.6%) between embryos that were fertilized in vivo and zona drilled at the two-cell stage and embryos that were unmanipulated. CONCLUSIONS: These findings indicate that small gaps in the zona pellucida, such as those that result from micromanipulation, do not significantly alter the ability of embryos to withstand cryopreservation. PMID- 1740218 TI - Pharmacokinetics of methotrexate after local tubal injection for conservative treatment of ectopic pregnancy. AB - Methotrexate peak level after intratubal injection was found to be significantly lower than the accepted toxic level. After IM injection, MTX peak level and the AUC were found to be similar to the levels observed after intratubal injection. The advantage of tubal injection over IM injection is challenged. PMID- 1740219 TI - Incidence of bilateral adnexal disease in severe endometriosis (revised American Fertility Society [AFS], stage IV): should a stage V be included in the AFS classification? AB - Studying the incidence of bilateral adnexal disease and dense adhesions, two groups of patients with severe endometriosis were distinguished, suggesting that a stage V needs to be considered in the AFS classification. PMID- 1740220 TI - Contralateral tubal pregnancy after gamete intrafallopian transfer. AB - A case of EP after GIFT into the contralateral tube is presented. Hydrotubation with Earle's medium immediately before the GIFT cannot be excluded as a possible cause of gamete migration. The complete demise of the CL also demonstrates that trophoblast can implant and develop without steroidal support. PMID- 1740221 TI - Controlled micromanipulation of human sperm in three dimensions with an infrared laser optical trap: effect on sperm velocity. AB - Individual human sperm can be micromanipulated in three dimensions using a 1.06 microns Nd:YAG laser trap. Single sperm swimming with velocities in the range of 65 to 85 microns/sec can be trapped with 40 mW of power through 120 seconds without a deleterious effect on velocity. Even though it will be necessary to further evaluate the effects of laser light on specific functions of sperm, our data suggest that decreasing the time of manipulation to a minimum will increase the safety of the micromanipulation procedures. Laser traps may play a role in assisted reproductive technology by facilitating the selective transport of individual sperm. PMID- 1740222 TI - Ultrastructure sperm defects in addicts. AB - Addiction is a major problem confronting the whole world today. Disruption of interpersonal relationships, economic loss, and crimes against property are frequent consequences. Harm to the individual himself extends to all physiological systems. In the present study, we examined semen samples of six addicts by light and electron microscopy. Oligoasthenospermia was demonstrated in five patients, and necrospermia was observed in one patient. Severe degenerative changes of the sperm heads were noted. Granular condensation of the chromatin with nuclear vacuoles was demonstrated. Persistent cytoplasmic droplets were frequently observed. Degenerated tails showing fragmentation of the plasma membranes and numerical aberrations of the 9 + 2 configuration were also present, together with thickened and disorganized fibrous sheaths. These results confirm the deleterious effects of addiction on the entire sperm structure. PMID- 1740223 TI - Smoking and corpus luteum function. PMID- 1740224 TI - Tumor necrosis factor-alpha and sperm function? PMID- 1740225 TI - Clomiphene citrate and cervical mucus. PMID- 1740226 TI - Pre- and postweaning excretion of puberty-influencing chemosignals in house mice. AB - Pre- and postweaning excretion of urinary chemosignals that influence puberty in female house mice were tested. The dependent variable used to assess the effectiveness of urine samples collected from donor mice was the age of first vaginal estrus in young female mice. Preweaning excretion of the puberty-delaying chemosignal by females was affected by litter sex composition; this effect interacted with the age of the young donor females. In litters of all females, the substance occurred from about the age of 9 days and in litters with 6 females and 2 males the delay substance was released from about the age of 17 days. Grouping dams during gestation but not prior to conception resulted in excretion of the puberty-delaying substance in the female progeny from the age of 17 days or possibly earlier. Young male mice do not excrete the puberty-accelerating chemosignal prior to the age of puberty. However, giving young males injections of testosterone resulted in an earlier first excretion of the acceleratory signal, suggesting that the machinery for chemosignal production is operative prior to the time of sexual maturity. Caging young males with an adult female prior to puberty resulted in earlier excretion of the puberty-accelerating substance, while caging young males with adult males retarded excretion of the substance. The findings are discussed in terms of early hormone effects on behavior and with regard to consequences for the chemosignal systems in house mice. PMID- 1740227 TI - Contextual determinants of auditory learning in bobwhite quail embryos and hatchlings. AB - This study examined the ability of bobwhite quail embryos and hatchlings to learn an individual bobwhite maternal call. Results revealed that embryos could learn an individual maternal call and remember that call for at least 24 hr following exposure. In contrast, hatchlings reared socially in groups of same-age chicks during postnatal exposure to a maternal call did not demonstrate a preference for that familiar call at 24 hr following exposure. However, individual auditory recognition was exhibited by hatchlings reared in social isolation, suggesting that the perceptual and social complexity of the postnatal situation can disrupt or interfere with early auditory learning. Additional support for this view was the finding that embryos exposed to unusually early visual stimulation during prenatal exposure to a maternal call also failed to prefer that familiar maternal call in subsequent choice tests. The idea that early auditory learning capacity is determined more by context and experience rather than the organism's specific age or stage of development is discussed. PMID- 1740228 TI - Organization of the stretch response to milk in the rat fetus. AB - Intraoral infusion of milk reliably elicits a stretch response in the rat fetus. The fetal stretch response appears isomorphic to the stereotypic behavior exhibited postnatally by suckling rat pups during milk ejection. Using a procedure that permits direct fetal observation, milk infusions were delivered to rat fetuses on Day 20 or 21 of gestation. Infusion of milk promoted systematic changes in fetal behavior that culminated in expression of the stretch response nearly 3 min later. Interruption of this behavioral sequence prevented stretching, suggesting that a period of behavioral reorganization after milk infusion is necessary but not sufficient for the stretch response to occur. The behavioral sequence initiated by the fetal rat's first exposure to milk is remarkably similar to the behavior exhibited by experienced infant rats at the nipple. PMID- 1740229 TI - Developmental constraints on the expression of behavioral and heart-rate orienting responses: II. The role of ambient temperature. AB - The effect of ambient temperature on the expression of behavioral and heart-rate orienting responses to a novel olfactory stimulus was examined in rats 1-18 days of age. There was no effect of ambient temperature on the behavioral orienting responses at any age. Ambient temperature did influence the expression of the heart-rate orienting response and did so differentially as a function of age. The implications of these findings for developmental models of attention and cognition are discussed. PMID- 1740230 TI - Consensus conference on research funding. PMID- 1740231 TI - Does it make you see red?: on the use of color in slides. PMID- 1740232 TI - Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. AB - Gastric ulcer is a multifaceted, pluricausal illness. Knowledge of the pathophysiology of gastric ulcer disease remains incomplete. Current pharmacological management of gastric ulceration is directed primarily at the reduction or neutralization of gastric acid secretion despite evidence that patients with this disease often exhibit normal gastric secretory activity. Attempts have been made to prevent or reduce gastric mucosal injury by cytoprotective agents without diminishing gastric acidity. We review several alternate explanations for the cause of gastric ulcers by examining various experimental models of gastric mucosal damage, including ethanol-, stress-, and nonsteroidal antiinflammatory drug-induced gastric lesions. We also discuss possible new strategies for the treatment of ulcer disease, particularly novel pharmacological targets arising from research conducted with these models. Growing realization that factors other than gastric secretion contribute significantly to the development of gastric ulcer disease prompts the conclusion that these same factors represent viable treatment alternatives. PMID- 1740233 TI - Molecular mimicry: a mechanism for autoimmune injury. AB - Many mechanisms may account for immune-mediated pathology after viral infections. Although several means have been hypothesized to play a role in disease, a widely accepted mechanism for viral-induced autoimmunity is molecular mimicry. It is thought that damage could result from an immune response to similar regions shared between virus and the host. Using computer-aided analysis, many sequence homologies have been identified between virus and host antigens. Using peptides corresponding to these regions, immunologic cross-reactivity has been found. In some cases, monoclonal antibodies to peptides of these regions have been shown to directly induce or augment disease in animal models. Using this approach to identify similar regions, it is possible to associate a known autoantigen with an infectious agent in autoimmune diseases in which there is no known etiologic agent. Conversely, it would also be possible to associate a known viral constituent with an unknown host antigen. Furthermore, identification of disease inducing regions of autoantigens or viral proteins may lead to immunotherapeutic approaches to establish tolerance or anergy to such disease-inducing regions. PMID- 1740234 TI - Diversity of structure, signaling and regulation within the family of muscarinic cholinergic receptors. AB - Acetylcholine signals through two types of unrelated membrane receptors referred to as nicotinic (nAChR) and muscarinic (mAChR) acetylcholine receptors. Nicotinic acetylcholine receptors were the first neurotransmitter receptors to be purified, cloned, and sequenced, and much is known about these proteins. In contrast, until 5 years ago relatively little was known about the muscarinic receptors. Since then there has been an explosion of information concerning the structure, signaling, and regulation of what is now known to be a family of muscarinic receptors. This review discusses the five identified members of the mAChR family and their coupling to the multiple G proteins that allow mAChRs to modulate many different types of signal transduction pathways. The five members of this family that have been identified so far have striking homology in their hydrophobic membrane domains but possess distinct cytoplasmic domains between the fifth and sixth membrane-spanning regions. These cytoplasmic domains appear to contain important determinants for receptor/G protein interaction and are likely to contain phosphorylation sites that regulate these interactions. mAChR agonists have been shown to induce phosphorylation of mAChR in intact cells, and the evidence that suggests that receptor phosphorylation may play a role in the regulation of receptor function is discussed. PMID- 1740235 TI - Electric power, pineal function, and the risk of breast cancer. AB - Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it is low in nonindustrialized areas. The search for the causes of breast cancer has not yet yielded a convincing explanation for the geographic and temporal patterns in the occurrence of breast cancer. Generation of electric power is a hallmark of industrialization, and two products of electric power, light-at-night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk. Exposure to either LAN or EMF can decrease production of melatonin by the pineal gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in experimental animals. Moreover, recent epidemiological findings indicate an increased risk of breast cancer in workers occupationally exposed to EMF. On the basis of these considerations, it is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies. PMID- 1740236 TI - Proteoglycans: many forms and many functions. AB - Proteoglycans are produced by most eukaryotic cells and are versatile components of pericellular and extracellular matrices. They belong to many different protein families. Their functions vary from the physical effects of the proteoglycan aggrecan, which binds with link protein to hyaluronan to form multimolecular aggregates in cartilage; to the intercalated membrane protein CD44 that has a proteoglycan form and is a receptor and a cell-binding site for hyaluronan; to heparan sulfate proteoglycans of the syndecan and other families that provide matrix binding sites and cell-surface receptors for growth factors such as fibroblast growth factor (FGF). One feature that recurs in proteoglycan biology is that their structure is open to extensive modulation during cellular expression. Examples of protein changes are known, but a major source of structural variation is in the glycosaminoglycan chains. The number of chains and their length can vary, as well as their pattern of sulfation. This may result in the switching of different chain types with different properties, e.g., chondroitin sulfate and heparan sulfate, and it may also result in the selective expression of sulfated chain sequences that have specific functions. The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs. Proteoglycan forms of proteins are thus important modifiers of the organization of the pericellular and extracellular matrices and modulators of the processes that occur there. PMID- 1740237 TI - Bone structure: from angstroms to microns. AB - Bone has a complex hierarchical structure, which despite much investigation, is still not well understood. Here we bring together pieces of this complicated puzzle, albeit from different sources, to present a tentative overview of bone structure. The basic building blocks are the extremely small plate-shaped crystals of carbonate apatite, just hundreds of angstroms long and wide and some 20-30 A thick. They are arranged in parallel layers within the collagenous framework. At the next hierarchical level these mineral-filled collagen fibrils are ordered into arrays in which the fibril axes and the crystal layers are all organized into a 3-dimensional structure that makes up a single layer or lamella of bone a few microns thick. The orientations of the collagen fibrils and the crystal layers in alternating lamellae of rat bone differ such that in the thinner lamellae, the fibrils and the crystal layers are parallel to the lamellar boundaries. In the thicker lamellae the fibrils are parallel to the boundary, but the crystal layers are rotated out of the plane of the boundary. In many bones these alternating lamellae are organized into even larger ordered structures to produce what is truly a remarkably ordered material, all the way from the molecular scale to the macroscopic product. PMID- 1740238 TI - Relationship of resistance to oxygen free radicals to CuZn-superoxide dismutase activity in transgenic, transfected, and trisomic cells. AB - Although CuZn-superoxide dismutase (CuZnSOD) has been shown to reduce oxidative damage in several systems, the quantitative relationship between the degree of protection and CuZnSOD activity has not been well investigated. Therefore, the ability of cells to tolerate superoxide toxicity was assessed as a function of endogenous CuZnSOD activity in several mouse and human cell lines with progressively higher levels of CuZnSOD activity. In five lines of fetal fibroblasts derived from SOD1-transgenic mice, with CuZnSOD activities of 1.7- to 7.1-fold the nontransgenic level and no changes in the cellular glutathione peroxidase (GSHPx) activity, a direct relationship (r = 0.97) between the LD50 to paraquat and enzyme activity was observed, suggesting that CuZnSOD activity is the single most important factor in determining the paraquat LD50. Mouse trisomy 16 fetal fibroblasts and human trisomy 21 lung fibroblasts, both expressing a 1.5 fold increase in CuZnSOD activity, were 1.5-fold more tolerant to paraquat than were their diploid counterparts. Furthermore, the protective effect of CuZnSOD at the DNA level, as shown by reduced thymine glycol generation, was demonstrated in paraquat-treated transgenic fibroblasts. A direct relationship (r = 0.78) of paraquat LD50 and CuZnSOD activity was also observed with a panel of six lines of SOD1- transfected HeLa cells with 1.6- to 7.3-fold the basal CuZnSOD activity. Moreover, there was no correlation between resistance to paraquat toxicity and the cellular GSHPx and/or catalase activity. Taken together, these results demonstrate a consistently protective effect of endogenous CuZnSOD against superoxide toxicity in both primary and transformed cell lines. PMID- 1740239 TI - Interleukin 1 protects hair follicles from cytarabine (ARA-C)-induced toxicity in vivo and in vitro. AB - ImuVert, a biologic response modifier, and interleukin 1 (IL 1) have been shown to protect the young rat from alopecia induced by cytarabine (ARA-C). In the present study the inhibition by ARA-C of DNA synthesis in hair follicles (HFs) and the protective effect of ImuVert and IL 1 were investigated in vivo and in vitro. Both ImuVert and IL 1 were equally effective in protecting rats from ARA-C induced alopecia. DNA synthesis in HFs isolated from ARA-C-treated animals was 10 20% of untreated controls. Follicles isolated from animals given either ImuVert or IL 1 before ARA-C exhibited normal DNA synthesis. In vitro, the incubation of normal rat HF with ARA-C resulted in 80% inhibition of [3H]-thymidine uptake. Preincubation of the follicles for 1 hr with IL 1 before the addition of ARA-C completely blocked the inhibition. Preincubation with imuVert, however, was less effective in blocking the inhibition from ARA-C. PMID- 1740240 TI - Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons. AB - A volatile anesthetic-gated current was characterized in patch-clamped cultured postnatal rat hippocampal neurons. In this preparation, the major volatile anesthetics, isoflurane, halothane, and enflurane, open an anion-selective conductance. This volatile anesthetic-gated current exhibits anion selectivity with a chloride-to-acetate permeability ratio of 15, shows outward rectification well described by the constant field equation, and is activated in a dose dependent fashion with half-maximal response to isoflurane at 0.8 mM (0.032 atm). The current persists in the absence of external Ca2+ and is not blocked by strychnine, a glycine antagonist. However, the gamma-aminobutyric acidA (GABAA) antagonists, bicuculline and picrotoxinin, and the nonspecific anion channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), completely block the response. These observations suggest that volatile anesthetics, like several other general anesthetics such as barbiturates, steroids, and etomidate, have a GABA-mimetic effect on vertebrate central neurons in culture. It is not clear whether this GABAA-gating property is a prerequisite for all general anesthetics. However, under normal physiological conditions of low intracellular Cl-, it is likely that drugs with both direct GABA agonist and GABA modulatory properties will produce overall depression of the central nervous system by increasing the normal inhibitory synaptic influence and by directly hyperpolarizing neurons. PMID- 1740241 TI - Role of [Ca2+]i in induction of c-fos, c-jun, and c-myc mRNA in rat PTE after oxidative stress. AB - Oxidative stress plays an important role in various types of cell injury and tumor promotion. Cells respond to oxidative stress in many ways including changes in membrane organization, ion movements, and altered gene expression, all of which contribute to the subsequent fate of affected cells. In this study, we investigated the expression of the proto-oncogenes c-fos, c-myc, and c-jun, which play a key role in proliferation and differentiation, using primary cultures of rat proximal tubular epithelium exposed to oxidative stress generated by the xanthine/xanthine oxidase system. This system generates superoxide and H2O2 in the extracellular space stimulating the release of active oxygen species from inflammatory cells. c-fos mRNA was expressed within 15 min, peaked at 30 min, and returned to constitutive levels by 3 h. c-jun mRNA began to rise after 30 min, peaked at 120 min, and remained above the constitutive levels up to 180 min. c myc mRNA expression was less affected by the treatment, with levels increasing gradually over the 180 min period. The expression of c-fos was inhibited by superoxide dismutase but not by catalase and was super-induced by cycloheximide. H2O2 alone did not induce any c-fos mRNA in this system. Chelation of extracellular ionized calcium by EGTA or of intracellular ionized calcium by Quin 2/AM resulted in a marked decrease of c-fos expression. Two protein kinase C inhibitors, H-7 and staurosporine, partly diminished the expression of c-fos, whereas a third, 2-aminopurine, which has a broader spectrum of inhibiting protein kinases, almost completely abolished it. A poly ADP-ribosylation inhibitor, 3-aminobenzamide, had no effect on c-fos expression in this system. Our results show that oxidative stress provokes sequential expression of c-fos, c jun, and c-myc, mRNA in this order. This c-fos expression appears to be largely controlled by calcium ion movement, which could include protein kinase C activation. Another protein kinase or kinases also appear to play an important role. PMID- 1740242 TI - Advances and controversies in blood coagulation: a 50-year retrospective. PMID- 1740243 TI - Federation of American Societies for Experimental Biology. 1992 FASEB meeting. Anaheim, California, April 5-9, 1992. Abstracts. Part I. PMID- 1740244 TI - 1992 FASEB meeting. Anaheim, California, April 5-9, 1992. Abstracts. PMID- 1740245 TI - Oral status and resident well-being in a skilled nursing facility population. AB - We studied the relationship between oral status and well-being in dentate and edentulous institutionalized residents through interviews with and dental examinations on 58 men and women. Oral status (measured by oral function, dental problem self report, soft tissue anomalies, and dry mouth) and well-being (measured by affect balance, self-esteem, health status, and nurse's ratings) were similar for dentate and edentulous subjects. Multiple regression analyses indicated oral status was significantly related to well-being. Unexpectedly, the extent of caries and plaque was also positively related to well-being, suggesting complex relationships between oral status markers and well-being in institutional settings. PMID- 1740246 TI - Psychosocial needs and care in nursing homes: comparison of views of social workers and home administrators. AB - Nursing home social workers (n = 152) and administrators (n = 231) were asked to rate the relative importance of resident and family psychosocial needs and the frequency of functions performed by or expected to be performed by social workers to meet these needs. Overall, administrators rated 19 of 28 psychosocial needs higher in importance than did social workers. The two groups both rated as very important the needs of support during the transition to the nursing home, help in dealing with loss, and help with relatedness and intimacy issues, though the groups rated high-frequency functions somewhat differently. PMID- 1740247 TI - Reconsidering the life review: the social construction of talk about the past. AB - The ostensible natural propensity of the elderly to talk about the past is reconsidered from a social constructionist perspective, offering a sociological alternative to Robert Butler's life review interpretation. Data from life narrative interviews with 30 near-centenarians are used to illustrate the importance of situated narrative challenges for initiating the construction and communication of life stories. Life stories are presented as social constructions made necessary and shaped by the demands of specific social situations. PMID- 1740248 TI - Psychiatric consultation to a continuing care retirement community. AB - Life care communities provide a continuum of residential services to the elderly. This report describes the provision of on-site psychiatric consultations to 82 individuals residing in one such community. Dementia and major depression were the most common diagnoses made. PMID- 1740249 TI - "Ideal" SCU not so ideal. PMID- 1740250 TI - Unblocking hospital beds. PMID- 1740251 TI - Aged heterogeneity: fact or fiction? The fate of diversity in gerontological research. AB - Studies examining age-related changes typically report findings as age-based generalizations that neglect the phenomenon of variability in gerontological research. This paper examines the degree of attention given in 185 studies to individual differences and the empirical patterns of variability reported in those studies that present measures of dispersion. Measures of dispersion were reported in 43% of the gerontological studies reviewed and in 24% of the developmental studies. Overall, a majority of all gerontological studies presenting data reported increases in variability with increasing age (65%). This pattern was more pronounced in longitudinal studies than in cross-sectional ones. PMID- 1740252 TI - Service use among low-income minority elderly: strategies for overcoming barriers. AB - The 1987 amendments to the Older Americans Act mandate a special effort to serve low-income minority elderly persons. A literature review showed that "practice oriented" research on service use has focused primarily on identifying barriers with much less attention to identification of strategies for overcoming the barriers. This paper identifies and describes strategies used throughout Texas. Strategies addressing the "lack of knowledge" barrier included use of influential groups, working with significant individuals, and the media. Strategies addressing the "lack of access" barrier included transportation, affordability, and availability. Strategies addressing the "lack of intent" barrier focused on cultural differences, making services attractive, and overcoming negative attitudes toward service use. PMID- 1740253 TI - Predicting the volume of health and social services: integrating cognitive impairment into the modified Andersen framework. AB - This investigation examined cognitive impairment as a predictor of the volume of community services used by older adults. Predictors of service volume were selected according to the modified Andersen framework and tested with 97 health care and 246 social service clients of a large multiservice agency. Results for health care clients showed that the effects of four predictors differ depending on clients' level of cognitive impairment; living arrangement, presence of secondary caregivers, client depression and task burden of the primary caregiver. No differences in predictor of social service use were observed for cognitively impaired and lucid clients. PMID- 1740254 TI - Veteran interstate migration and VA health service use. AB - Resource allocations within the VA health care system are based in part on the number of veterans in an area plus the number of veterans expected to move into the area. This paper examines the relative importance of geographic mobility as a factor affecting the use of VA health services by the older veteran population in the U.S. Using a variety of secondary data sources, we found that the variation in state VA health service admission rates is better explained primarily by the characteristics of the resident nonmobile veteran population and the characteristics of veterans migrating to the state, not just by their numbers. Health care demand projections should take these findings into account. PMID- 1740255 TI - Efficacy of nursing home preadmission screening. AB - This study evaluates the efficacy of four state nursing home preadmission screening instruments. Using data from three community-based services demonstration experiments, the screens were compared on measures of sensitivity, specificity, and proportions of false negatives and false positives. Results indicate that the more restrictive screens tended to have lower sensitivity but higher specificity, and to generate a higher proportion of false negative decisions than the more liberal screens. Overall rates of correct prediction were higher for the more restrictive screens. Results highlight differences in eligibility restrictiveness across states as well as possible tradeoffs of cost containment and access in designing a preadmission screen. PMID- 1740256 TI - Differential effects of daughters' marital status on their parent care experiences. AB - This study compared the parent care experiences of five groups of daughters (N = 492) (married, remarried, separated/divorced, widowed, and never married). Data include demographic characteristics and measures of depression, positive affect, personality strength, health, social support, relationship quality, caregiving burden, caregiving mastery, and caregiving satisfaction. Women with husbands had more socio-emotional and instrumental support, much higher incomes, less financial strain from caregiving, and less depression. They felt their own particular marital status made caregiving easier than did the three groups of not married women. PMID- 1740257 TI - Status transitions and future outlook as determinants of conflict: the caregiver's and care receiver's perspective. AB - This study examined the effects of status transitions and future outlook on conflict from the perspective of both caregiver and care receiver. As predicted, future outlook had a powerful association with dyadic conflict. Other strong predictors of conflict for care receivers were current state of happiness and changes in the relationship over a 3-year period. For caregivers, conflict was associated with care receivers' lack of social participation with family and friends, and changes in dyadic relationship. PMID- 1740258 TI - Retirement intentions among black professionals: implications for practice with older black adults. AB - This study examined the preretirement intentions of black professionals. The sample consisted of 234 blacks and was stratified by gender, age, and professional status. Based on a model developed for predicting the retirement intentions and attitudes of a sample of white professionals, six categories of independent variables (sociocultural, work history, alienation, leisure and social activities, financial planning, and plans for retirement life) were included in the analysis. Professionals who were highly committed to their work, had few financial investments, and socialized primarily with co-workers tended to avoid planning for retirement. These results have important implications for practitioners concerned with more effectively meeting the preretirement and retirement needs of older black adults. PMID- 1740259 TI - Availability of personal transportation in households of elders: age, gender, and residence differences. AB - Using data from the 1% Public Use Microdata Sample of the 1980 Census of Population and Housing, we examined correlates of the availability of personal transportation in the households of elders. Results indicate that the availability of vehicles decreases with age, is highest for rural farm and lowest for central city residents, and is lower for women. Only 1.3% of rural farm men 65-74 lack access to a vehicle, but 57.8% of central city women 85 + are without personal transportation in their households. PMID- 1740260 TI - Age differences and correlates of worrying in young and elderly adults. AB - A cross-sectional investigation compared worry and its correlates in elderly people (N = 89) and in college students (N = 74). Consistent with prediction, the elderly adults expressed significantly fewer worries than the college students about finances and social events. Both groups were equally worried about health issues. The elderly scored higher on the Bradburn Affect Balance Scale, scored in the external direction on the Nowicki-Strickland Locus of Control Scale, and were more oriented toward the past and present than the future. Worry in the elderly was related to less favorable attitudes toward the future, and among college students worry was related to negative attitudes toward the present. For both age groups, an external locus of control was associated with higher worry scores. PMID- 1740261 TI - Factors influencing hospital patients' preferences in the utilization of life sustaining treatments. AB - Ninety-seven elderly hospitalized patients were asked about their preferences for several treatments under three hypothetical levels of future cognitive functioning: intact, confused, and unconscious. Levels of cognitive functioning and depression were also assessed. Sixty-six percent of the patients were more likely to want treatment if they expected to be cognitively intact than when a future condition involved impaired cognition; 36% did not want any treatment in at least 75% of the conditions; and 16% wanted treatment in at least 75% of the conditions studied. A minority (12%) did not show any pattern in their preferences. The absence of a definite pattern was related to lower levels of education and to higher levels of depressive symptoms. Patients self-reported their preferences for treatments being influenced most by their personal values, religion, and by experiences with illnesses of others. PMID- 1740262 TI - Decisional control in moving to a nursing home: postadmission adjustment and well being. AB - Five hundred and two skilled nursing facility residents were measured with a multidimensional assessment instrument within 4 weeks of admission, and then at 3 and 12 months following baseline, to determine the impact of deciding and wanting to make the move on well-being and adjustment. Dependent variables included measures of physical, social, and psychological functioning, social interaction, activity, satisfaction with services, and discharge. Regression analyses suggest an interactive effect on ADL change at 3 months. PMID- 1740263 TI - The molecular revolution--coming your way soon. PMID- 1740264 TI - Longitudinal study of gall stone prevalence at necropsy. AB - A prospective study of the prevalence of gall stone disease at necropsy in a stable population has been undertaken over a 10 year period up to June 1988. In women, the prevalence of gall stone disease remained static but in men aged 50-59 years it rose from 7% (n = 148) in the first three years to 18% (n = 138) in the last three years (p less than 0.01) and in men aged 60-69 it rose from 12% (n = 370) to 20% (n = 366, p less than 0.01). In the latter age group the female: male ratio fell from 2:1 to 0.8:1. The proportion of deaths from coronary heart disease in men fell slightly in those over 70 during the study period. There was a fall in deaths from coronary heart disease in all age groups in women. Men with gall stones were less likely to have had a cholecystectomy than women, and overall 88% of gall stones remained in situ. In a parallel clinical study, the number of cholecystectomies carried out in the same district fell by 18% over the 10 years without any apparent change in the provision of resources. Cholecystectomy remained almost three times more frequent in women. National data indicate that there have been major changes in the average diet before and during the period of study in favour of reducing coronary heart disease. There has been no change in mortality from coronary heart disease in young men but if the observed increase in the prevalence of gall stones in men and the decrease in deaths from coronary heart disease in women are real phenomena, it seems likely that they are diet related. PMID- 1740265 TI - High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits. AB - Over a three year period (1 July 1986 to 30 June 1989) all newly diagnosed and histologically proved cases of oesophageal and gastric cancer were recorded prospectively. Some 1515 cases of oesophageal cancer (1050 men and 465 women) and 966 cases of gastric cancer (789 men and 177 women) were registered. Seven patients had simultaneous oesophageal and gastric cancer. Age standardised incidence rates for oesophageal cancer were: men 43.6/100,000 per year; women 27.9/100,000 per year. The rates for gastric cancer were: men 36.7/100,000 per year, women 9.9/100,000 per annum. These figures were three to six times higher than those recorded by cancer registries in Banglore, Madras, and Bombay. The incidence rates for oesophageal and gastric cancer in Islamabad (southern district of Kashmir) were 4.1 to 5.4 times higher in men and 1.5 to 2.0 times higher in women than those for Kupwara (northern district of Kashmir). The incidence rates for oesophageal and gastric cancer in Muslims, Hindus, and Sikhs were different. The epidemiology of oesophageal cancer in Kashmir was similar to that found in the 'Asian oesophageal cancer belt'. At the same time Kashmir also had an unprecedented high incidence of gastric cancer. Kashmiries have special personal and dietary habits. Further studies are needed to define the relation between these habits and the occurrence of oesophageal and gastric cancer. PMID- 1740266 TI - Alternative method of positioning the pH probe for oesophageal pH monitoring. AB - The most reliable method of positioning a pH probe for oesophageal pH monitoring is to use manometry to determine the upper margin of the lower oesophageal sphincter and to place the probe 5 cm above this point. Manometry is expensive, however, requires special equipment and training, and is not widely available. An alternative cheaper way of determining the site of the lower oesophageal sphincter has been evaluated. A fine bore nasogastric tube with a latex balloon at its tip was inserted transnasally into the stomach. The balloon was inflated with 10 ml of water and the tube withdrawn until resistance was met. The distance from the nose (in cm) was noted and compared with the upper margin of the lower oesophageal sphincter as determined by oesophageal manometry. The manometric distance agreed closely with the balloon distance minus 1 cm (bias 0.29 cm; 95% CI of bias, 0.03 to 0.55 cm; 2 SD, limits of agreement, 1.58 cm). We conclude that where oesophageal manometry is not available, balloon localisation is a suitably accurate way of identifying the lower oesophageal sphincter. PMID- 1740267 TI - Comparison of aspiration and scintigraphic techniques for the measurement of gastric emptying rates of liquids in humans. AB - A comparison was made of two techniques to measure the rate of gastric emptying. A noninvasive scintigraphic technique using a gammacamera and an invasive aspiration technique based on dye dilution were performed simultaneously. Seven healthy male volunteers each consumed two different liquid meals on two separate occasions. Scintigraphic measurements were performed continuously with aspiration every 10 minutes for a total of one hour. Gastric emptying rates were expressed as slope values after semilog linearisation of the emptying curves. Agreement between the two methods was assessed from the individual differences and mean of the two techniques, as well as from the geometric mean, including 95% limits of agreement. The scintigraphic technique gave a 70% slower emptying rate than the dye dilution technique. However, the 95% limits of agreement are large (1.56 to 0.30), reflecting the small sample size and the large coefficient of variation in the techniques used. PMID- 1740268 TI - Intestinal lymphangiectasia associated with angiofollicular lymph node hyperplasia (Castleman's disease). AB - A patient presenting with predominantly gastrointestinal symptoms and a history of myocardial infarction was found to have ascites, hepatosplenomegaly, para aortic lymphadenopathy, thrombocytosis, and a paraproteinaemia. A jejunal biopsy specimen showed lymphangiectasia and histology of the spleen and lymph nodes showed angiofollicular hyperplasia or Castleman's disease of the hyaline vascular type. This association has not previously been described and, moreover, systemic symptoms are unusual in this variant of Castleman's disease. PMID- 1740269 TI - Rectal lymphoma after colectomy for ulcerative colitis. AB - Primary colonic lymphoma is an increasingly recognised complication of ulcerative colitis. We report the first known case of rectal lymphoma occurring after colectomy and ileorectal anastomosis in ulcerative colitis. PMID- 1740270 TI - Can Crohn's disease be diagnosed at laparotomy? AB - The typical macroscopic features of Crohn's disease have been well described and are widely regarded as sufficient to diagnose the disease at laparotomy. We report six patients undergoing laparotomy for symptomatic Crohn's disease, shown radiologically, who were found to have macroscopically normal small bowel despite careful examination of the bowel by an experienced surgeon. In four cases resection was deferred, but all subsequently deteriorated and required further surgery. Minor abnormalities found by balloon examination of the terminal ileum prompted resection in two further patients. Histology showed an unusually superficial distribution of inflammation, which could explain the negative findings at laparotomy. We conclude that normal laparotomy findings alone do not exclude a diagnosis of clinically important small bowel Crohn's disease. Crohn's disease should be considered in patients with persisting symptoms after negative laparotomy. PMID- 1740271 TI - Intestinal metaplasia and Helicobacter pylori: an endoscopic bioptic study of the gastric antrum. AB - To study the relationship between intestinal metaplasia and Helicobacter pylori infection, 2274 gastroscopic antral biopsies taken from 533 patients were examined. Overall, intestinal metaplasia was found in 135 patients (25.3%) and H pylori in 289 patients (54.2%). The prevalence of intestinal metaplasia and H pylori was age related, being more common in patients greater than or equal to 50 years compared with patients less than 50 years (intestinal metaplasia, p less than 0.001 and H pylori, p less than 0.05). Intestinal metaplasia was found more often in H pylori positive patients compared with H pylori negative patients (33.9% v 15.2%, p less than 0.001). The mean age of intestinal metaplasia positive patients who were also H pylori positive was 64 (13.3) years, whereas the mean age of intestinal metaplasia positive patients who were H pylori negative was 72 (14.7) years (p less than 0.005). The extent of intestinal metaplasia was not statistically different in the latter two groups. Although our data do not prove a causal relationship between H pylori infection and the histogenesis of intestinal metaplasia it is suggested that H pylori infection is an important factor in the development of intestinal metaplasia, which is generally recognised as a precursor lesion of intestinal type gastric carcinoma. PMID- 1740272 TI - Gastric emptying of liquid in children suffering from acute rotaviral gastroenteritis. AB - Nausea and vomiting commonly occur in children suffering from rotaviral diarrhoea. Gastric emptying was studied in 10 children (age six to 12 months) suffering from acute diarrhoea caused by rotavirus using a dye dilution double sampling technique. The test meal was 5% dextrose in water and this test was repeated 12 weeks after recovery. The median (range) of the percentages of the liquid meal remaining in the stomach at 5, 10, 20, 40, and 60 minutes after instillation of the meal were 82 (79-90), 70 (61-86), 51 (38-76), 26 (14-53), and 13 (2-35) respectively in the acute stage, whereas after the recovery period the values were 76 (70-79), 58 (49-63), 33 (24-40), 11 (2-26), and 3 (0-7). The differences were statistically significant. The half time of gastric emptying (t1/2) was 19.5 (14-30) minutes in acute stage, and 13.1 (10-15) minutes during follow up (p less than 0.01). Rotaviral gastroenteritis is accompanied by abnormal gastric motor function, as manifested by delayed emptying of a liquid meal. PMID- 1740273 TI - Cysteamine protects gastric epithelial cell monolayers against drug induced damage: evidence for direct cellular protection by sulphydryl compounds. AB - The sulphydryl containing drug cysteamine protects gastric mucosa in vivo against acute injury. It is not known whether this protection includes a direct effect on gastric cells. Using gastric epithelial cell monolayers derived from a well differentiated human cell line, we evaluated whether cysteamine protects against taurocholate or indomethacin induced damage in conditions which completely exclude the influence of vascular, hormonal, and neural factors. The effect of cysteamine on prostaglandin production by monolayer cells in vitro was also assessed. Cysteamine decreased damage brought about by sodium taurocholate and indomethacin by 40% (p less than 0.01) and 50% (p less than 0.01) respectively. The sulphydryl blocker iodoacetamide prevented the protective effect of cysteamine. Pretreatment with indomethacin, which inhibited prostaglandin E2 output by 60%, did not prevent protection by cysteamine; incubation with cysteamine decreased prostaglandin E2 production by cultured cells. We conclude that (i) cysteamine directly protected gastric epithelial cells in vitro (ii) this protection occurred with indomethacin, which interferes with cellular metabolism of prostaglandins, and taurocholate, whose damaging action at neutral pH is unrelated to interference with prostanoid metabolism, (iii) cysteamine protection in vitro is unrelated to endogenous prostaglandins and is probably mediated by endogenous sulphydryl compounds. PMID- 1740274 TI - Production of epithelial cell growth factors by lamina propria mononuclear cells. AB - The effects of lamina propria mononuclear cell culture supernatant on epithelial cell DNA synthesis were studied using cells isolated from patients with inflammatory bowel disease and normal controls. Supernatants from resting and phytohaemagglutinin stimulated cells were studied and supernatants that strongly promoted DNA synthesis were pooled, and growth factor activity partially characterised. The effects of recombinant interleukins-1 beta,2,3,interferon gamma, and granulocyte macrophage colony stimulating factor were tested in the same system. Resting lamina propria mononuclear cells produce factors that increase DNA synthesis. Production of these factors is increased by phytohaemagglutinin stimulation. No significant differences were found in production of these factors between patients with inflammatory bowel disease and normal controls. The molecular weight of the active factor(s) lies in the region 31-48 kD. Chromatofocusing produced two peaks of activity, one in the region pk 5.5 and one around pk 6.4. The activity was heat and acid pH labile. Activity was not destroyed, however, by 0.05% trypsin. Recombinant granulocyte macrophage colony stimulating factor was a weak stimulus to epithelial DNA synthesis, interleukin-1 beta was weakly inhibitory but other cytokines tested did not have any effect. Granulocyte macrophage colony stimulating factor is probably important in controlling epithelial cell growth. PMID- 1740275 TI - Oral submucosal fibrosis--a preventable disease. PMID- 1740276 TI - Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man. AB - The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment. PMID- 1740277 TI - Mr 40,000 human colonic epithelial protein expression in colonic mucosa and presence of circulating anti-Mr 40,000 antibodies in cotton top tamarins with spontaneous colitis. AB - Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon. PMID- 1740278 TI - Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease. AB - Concentrations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and soluble IL-2 receptors (sIL-2R) were determined by enzyme linked immunosorbent assays (ELISA) in supernatants of sonicated endoscopical mucosal biopsy specimens from 31 patients with inflammatory bowel disease and 19 controls. IL-1 beta was detected in 53% of the patient supernatants (p = 0.0001), IL-2 in 35% (p = 0.0031), compared with none of the controls. Soluble IL-2R was present in 55% and 26% of the specimens, respectively (p = 0.07). The concentrations of IL-1 beta (p = 0.00015), IL-2 (p = 0.0019), and sIL-2R (p = 0.0073) were highest in the most inflamed biopsy specimens, compared with less inflamed specimens and controls. There were no significant differences in IL-1 beta, IL-2, and sIL-2R concentrations between ulcerative colitis (16) and Crohn's disease patients (15). The results suggest that enhanced cellular immunity operates in vivo at the mucosal level in active inflammatory bowel disease. PMID- 1740280 TI - Distribution of collagenous colitis: utility of flexible sigmoidoscopy. AB - We investigated the distribution of the collagen band in 33 patients with collagenous colitis to estimate the likelihood of the disease being diagnosed in biopsy specimens from the left side of the colon, such as those obtained using flexible sigmoidoscopy. To be included in this study patients had a subepithelial collagen band greater than or equal to 10 microns, an increase in chronic inflammatory cells in the same specimen, and diarrhoea for which there was no other apparent cause. In 17 patients undergoing full colonoscopy with a thickened collagen band, collagenous colitis was frequently patchy, even though overall the thickened collagen band was almost equally distributed throughout the colon. Rectal biopsy specimens showed a normal collagen band in 73% of patients, while a thickened collagen band was found in 82% of patients in at least one specimen from the left side of the colon. Three patients had a thickened collagen band only in the caecum. In three of eight rectal biopsy specimens with a normal collagen band there was no mucosal inflammation to raise the possibility of proximal disease, although all but one specimen with a normal collagen band from the sigmoid and descending colon were inflamed. Rectal biopsy alone is therefore a relatively poor method of making the diagnosis. Flexible sigmoidoscopy with multiple biopsy specimens from several sites is a reasonable initial investigation but not sufficient to exclude collagenous colitis when based on the presence of a thickened collagen band alone. Should left sided biopsy specimens show a normal collagen band but an inflamed mucosa, total colonoscopy with multiple specimens including the caecum may be required to establish the diagnosis. PMID- 1740279 TI - Salicylates used in inflammatory bowel disease and colchicine impair interferon gamma induced HLA-DR expression. AB - Colonic epithelial cells express HLA-DR in inflammatory bowel disease. The effect of drugs used in the treatment of inflammatory bowel disease and colchicine on interferon-gamma (IFN-gamma) induced DR expression has been investigated. HT-29 cells were cultured in 25 cm2 flasks. At 48 hours interferon-gamma (0, 50, or 100 U/ml) +/- drug were added. At 120 hours the cells were stained for HLA-DR and analysed by flow cytometry. 10(-2) M 5ASA reduced DR expression induced by 50 U/ml interferon-gamma from 62 (12)% of cells (mean SD) to 29 (20)% (p less than 0.005). Corresponding figures for 10(-2) M N-acetyl 5ASA were 68 (16)% to 39 (17)% (p less than 0.05); for 10(-2) M 4ASA, 61 (4)% to 57 (4)% (p = 0.6); for 10(-2) M N-acetyl 4ASA, 60 (12)% to 35 (13)% (p less than 0.05); for 10(-2) M olsalazine, 72 (9)% to 3 (1)% (p less than 0.001); for 10(-3) M olsalazine, 72 (9)% to 16 (10)% (p less than 0.001); for 10(-6) M colchicine, 62 (13)% to 5 (3)% (p less than 0.001); and for 10(-7) M colchicine, 62 (13)% to 10 (3)%. Similar results were obtained when DR was induced by 100 U/ml of interferon-gamma except with 10(-2) M 4ASA which reduced expression from 77 (4)% to 68 (3)% (p less than 0.05). Sulphapyridine, prednisolone, indomethacin and cyclosporin A had no effect. Concurrent staining with propidium iodide showed that these results were unchanged when viable cells alone were analysed. Prior incubation of cells with drug, followed by washing, had no effect on interferon-gamma induced DR expression. 5ASA, N-acetyl 5ASA, 4ASA, N-acetyl 4ASA, olsalazine and colchicine reduce interferon-gamma induced HLA-DR expression. In inflammatory bowel disease these compounds may impair antigen presentation by the colonic epithelium. PMID- 1740281 TI - Oesophageal clearance of small amounts of equal or less than one millilitre of acid. AB - The oesophageal acid clearance time was evaluated in 10 healthy volunteers of 'small' boluses of 0.5 and 1 ml and 'minute' boluses of 0.05 and 0.1 ml 0.1 N HCl, as well as 0.1 and 1 ml 0.01 and 0.001 N HCl. Swallow rate was normalised at q 60 seconds. For 0.1 ml 0.1 N HCl, acid clearance time was also measured for swallow intervals of q 30 and 120 seconds. Acid clearance time to restore pH to 4.0 was significantly longer (p less than 0.01) for the 0.5 and 1 ml 0.1 N HCl (210 and 273 seconds, respectively) than for the 0.05 and 0.01 ml acid boluses (83 and 94 seconds, respectively). The minimum acid clearance time was 18 seconds (0.05 ml 0.1 N HCl). Acid clearance time for 0.1 N HCl was less than one minute on only two occasions. The acid clearance times were comparable when the subjects sat upright. A longer interswallow interval--that is, 120 seconds, resulted in a significantly longer acid clearance time than shorter swallow intervals (p less than 0.05). Oesophageal acid clearance time for small acid volumes averaged more than three minutes and for minute acid volumes was generally more than one minute; and acid clearance times were comparable for the supine and upright postures, while gastrooesophageal reflux episodes causing pH drops to 3-4 may last for less than 15 seconds, substantial oesophageal pH drops to less than or equal to 1.5 that persists less than 15 seconds are difficult to be attributed to true gastrooesophageal reflux. PMID- 1740282 TI - Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine. AB - In vivo bromodeoxyuridine (BrdUrd) labelling of the human large bowel was performed and a detailed histochemical localisation of label in sections of crypts was undertaken using a monoclonal antibody to BrdUrd containing DNA. Flow cytometric studies on extracted nuclei were also performed (data presented elsewhere). The average crypt in the human large bowel (excluding the rectum) was 82 cells in height and 41 cells in circumference, with a total of about 2000 cells (assuming a topographical correction factor of 0.6). Ten per cent of the cells were replicating their DNA--that is, were in the S phase of the cell cycle- and 0.4% were in mitosis. The median position for the labelling index versus cell position frequency plot is at the 20th cell position--at a quarter of the crypt height. The lower and upper limits of the cell proliferation are given by the 5th and 95th percentiles at cell positions 4 and 43 respectively. The peak labelling index is about 30% and it occurs at cell position 15. The labelling index at the crypt base, the probable stem cell zone, is about 14%, suggesting that these cells have a longer cell cycle. Taking a value of 8.6 hours for the duration of the S phase (deduced from the flow cytometric data) and assuming a growth fraction of 1.0 for the mid-crypt, these data provide an estimate of about 30 hours for the cell cycle time. The rectal crypts are about the same size but contain about 30% fewer S phase cells. The data also yielded a per cent BrdUrd labelled mitosis curve. PMID- 1740283 TI - Oesophageal motility, luminal pH, and electrocardiographic-ST segment analysis during spontaneous episodes of angina like chest pain. AB - The relation between oesophageal motility, luminal pH, and spontaneous pain events in 47 patients with recurrent angina like pain and normal coronary arteries was investigated. Preliminary investigation by conventional station pull through manometry (SPTM), was followed by a 24 hour period of ambulatory oesophageal motility and luminal pH monitoring. Computerised analysis of motility and pH data recorded during chest pain was then compared with pre-elected control samples taken before and after symptoms. Concurrent real time electrocardiographic (ECG)-ST segment analysis was performed to catalogue any ECG STT wave changes indicative of myocardial ischaemia. SPTM showed a high group percentage incidence of simultaneous contractions (mean (SD) 11.1 (2.3)%) and a raised lower oesophageal sphincter tone (57.4 (15.2) mm Hg). During ambulatory monitoring, 35 patients experienced one or more episode of angina, providing a total of 59 pain events, although no significant change in group motility and reflux parameters peculiar to episodes of chest pain were found. Ischaemic ECG changes were detected in 10 (21%) patients, but were accompanied by pain in only two. Independent analysis of the ECG traces corresponding to these purported ischaemic ECG events determined them unequivocal in three patients and probable in a further two. No apparent correlation was noted, however, between these ECG events and corresponding patterns of motility or reflux. PMID- 1740284 TI - Estimation of total hepatic blood flow by duplex ultrasound. AB - The volume flow rate of blood in the portal vein and the hepatic artery was measured using a duplex ultrasound system. Two sections of the hepatic artery were studied; the common hepatic artery where measurements were made just after the bifurcation of the coeliac axis to splenic and hepatic arteries and the hepatic artery itself, where measurements were made just proximal to the porta hepatis in a straight stretch of artery overlying the portal vein. Total hepatic blood flow was taken as the sum of hepatic artery and portal vein flows. A group of 10 normal healthy volunteers in the fasting state was studied. The mean (SD) volume blood flow in the vessels was measured to be: hepatic artery 3.5 (45%) ml/min/kg, common hepatic artery 6.9 (30%) ml/min+/kg, portal vein 13.5 (21%) ml/min/kg, total hepatic flow 17.0 (16%) ml/min/kg. PMID- 1740285 TI - Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure: relation to other prognostic indicators. AB - The value of coagulation factor V and VIII/V levels as prognostic indicators was assessed in 27 patients with fulminant hepatic failure and compared with other predictive indices. Admission factor V levels were significantly reduced in 22 patients with paracetamol induced hepatic failure compared with a healthy control group (median 9.5% v 103%, respectively; p less than 0.001) and with lower values in non-A non-B hepatitis (median 2.7%). Values in the seven patients who died after paracetamol overdose, considered together with the four who underwent liver transplantation (group median 5.1%), were significantly lower than in the 11 who survived (median 11.8%; p less than 0.01). Median admission factor VIII was higher in those who died or received a transplant than in those who survived (298% v 162%; p less than 0.05), with both results higher than in healthy volunteers (median 104%; p less than 0.01) but lower than in non-A non-B hepatitis (median 340%). The ratio of factor VIII/V on admission was less than 30 in all patients who survived paracetamol overdose (median 17) with corresponding values greater than 30 in 10 of 11 of those who died (median 39). A factor V result less than or equal to 10% on admission predicted an adverse outcome in 10 of 11 fatal cases, a 91% sensitivity which was greater than for the previously defined indicator of an arterial blood pH less than 7.30 on admission (sensitivity 82%). Prothrombin time at admission or on day 4 did not usefully predict outcome in our series. Predictive accuracy was 73% and 82% for factor V and admission acidosis respectively and 95% for factor V in conjunction with admission coma grade III or IV and factor VIII (ratio > 30). These criteria may be useful in selecting patients with paracetamol induced fulminant hepatic failure for transplantation. PMID- 1740286 TI - Tracking personal spending on health care. PMID- 1740287 TI - Clinical quality initiatives: the search for meaningful--and accurate--measures. AB - At times, it seems as though every hospital, hospital association, philanthropic foundation and major corporation in the United States is involved in the quality movement in health care. The explosion of quality measurement initiatives that began in the 1980s is continuing apace, with earlier programs being expanded, enhanced, modified and replicated throughout the country in a variety of settings. This cover story looks at the broad efforts to develop clinical quality measurement tools from four different perspectives. First, we provide an update on the Maryland Quality Indicator Project and its ongoing use as a role model for many of the newer clinical indicator projects now being developed. Part two looks at the Joint Commission on Accreditation of Healthcare Organizations and its Agenda for Change project, as well as other large-scale quality measurement programs under way in the private sector that are attempting to determine what indicators are meaningful to use. Part three examines the growing role of corporate payers in pushing hospital-comparison and other assessment programs forward. And in the final section, we look at the federal government's role in developing practice guidelines and outcomes research. PMID- 1740288 TI - Two largest national alliances fine-tune strategies as health care environment changes. Interview by Howard J. Anderson. AB - The nation's two largest alliances of not-for-profit hospitals and systems are refining their roles for the 1990s. American Health Care Systems (AmHS) and Voluntary Hospitals of America (VHA) are moving away from strategies designed for competition in the marketplace of the 1980s, and toward helping their members change the way they deliver health care in their communities. While AmHS is promoting its health care reform proposal, VHA sees its existing 29 regional organizations of hospitals as a potential infrastructure for the development of community-based, integrated networks of care as envisioned in the AHA's reform plan. Experts add that the alliances clearly have to go beyond group purchasing to serve the changing needs of their members. PMID- 1740289 TI - Pharmaceutical prices continue to drive up supply costs. AB - The 1992 purchasing outlook from the Joint Purchasing Corp. (JPC), New York City, forecasts a difficult winter followed by a mild economic recovery beginning in the spring or early summer. Pharmaceuticals, however, are forecast to undergo significant price increases, due in part to hospital pharmaceutical price hikes associated with the ramifications of the 1990 Medicaid drug rebate legislation passed by Congress. PMID- 1740290 TI - Survey: CEOs cite flaws in departmental IS. PMID- 1740291 TI - Hospitals use research to build physician links. PMID- 1740292 TI - Home care PPS demonstration edges forward. PMID- 1740293 TI - Hospitals face few problems with new OSHA vaccine rule. PMID- 1740294 TI - TQM: best antidote for MD practice problems. PMID- 1740295 TI - Pathology trainee attrition: a new variable in the manpower equation. PMID- 1740296 TI - Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. PMID- 1740297 TI - Myxoid heart disease: an assessment of extravalvular cardiac pathology in severe mitral valve prolapse. AB - Because of the microscopic features of the affected leaflets in mitral valve prolapse (MVP), myxoid degeneration of the valve is a common pathologic designation applied to this condition. We undertook this study as a means of gaining an insight into the occurrence and prevalence of extravalvular cardiac alterations in hearts with severe MVP. Tissues of 24 hearts with severe myxomatous transformation of the mitral valve as the sole cardiac abnormality were examined. Eighteen of the 24 subjects with severe MVP died suddenly. Only two of these had pathologic evidence of severe mitral insufficiency. Twenty-four normal hearts served as controls. The two groups of hearts came from victims of homicide, suicide, accident, or natural death. Sections of the mitral valve, working myocardium, conduction system, and cardiac nerves and ganglia were studied by routine and special connective tissue and proteoglycan stains. Similar to the findings in severely affected mitral valves, prominent deposits of proteoglycans in neural and conduction tissue readily distinguished hearts with myxomatous valve changes from the control hearts. We conclude that the commonly recognized local derangement of valvular tissue in MVP is but one specific reflection of a more general myxomatous alteration in cardiac connective tissue. PMID- 1740298 TI - Incidental myocarditis with intravenous drug abuse: the pathology, immunopathology, and potential implications for human immunodeficiency virus associated myocarditis. AB - Human immunodeficiency virus (HIV)-associated myocarditis is well reported. Many of these patients are also intravenous (IV) drug abusers. This study examined sudden death victims from the Office of the Chief Medical Examiner, State of Maryland, for active myocarditis. A group of HIV-negative drug abusers is compared with a group of HIV-negative victims without any known risk factors for the acquired immunodeficiency syndrome. Using modified Dallas criteria combined with an avidin-biotin-labeled immunoperoxidase procedure, the cases were classified as active, borderline, or absent myocarditis. Serologic analysis for circulating antimyocardial antibody was performed along with phenotypic analysis of the infiltrate. Of the 15 IV drug abuse cases examined, none were positive for HIV (enzyme-linked immunosorbent assay and Western blot). With IV drug abuse as the primary risk factor, five cases demonstrated active myocarditis, while five others had borderline myocarditis. Only one of 10 low-risk patients had a lymphocytic infiltrate consistent with borderline myocarditis. Drug abuse-related myocarditis was associated with cardiac pathology resulting in sudden death in only one case. Antimyocardial antibodies were positive in four of the 15 IV drug abuse cases, including patients with active, borderline, and absent myocarditis. The phenotypic expression of the lymphocytic infiltrates was similar to the findings reported for idiopathic and HIV-related myocarditis (Am J Pathol 137:1365-1371, 1990). Toxicology studies did not implicate any particular drug of abuse, but the increased frequency of myocarditis observed may reflect complications of cocaine or the combined effects of opiates and cocaine. Intravenous drug abuse is an independent risk factor for myocarditis and must be taken into consideration in studies of HIV-associated myocarditis. PMID- 1740299 TI - Infrequent detection of Toxoplasma gondii genome in toxoplasmic lymphadenitis: a polymerase chain reaction study. AB - The diagnosis of toxoplasmic lymphadenitis is currently established by histologic evaluation with confirmation by serologic studies. We used a sensitive and specific polymerase chain reaction methodology for the identification of toxoplasmic genomes previously reported by others to investigate whether this technology could contribute to the diagnosis. We were able to reliably detect toxoplasmic genomes in paraffin-embedded tissues of toxoplasmic encephalitis and myocarditis, and serial dilution studies indicated a high degree of sensitivity. Nonetheless, we identified toxoplasmic genomes in frozen tissue from only one of nine cases of toxoplasmic lymphadenitis. In the one positive case, only one of three frozen samples from the lymph node biopsy was positive, indicating a focal infection within the lymph node. It is concluded that polymerase chain reaction studies, at their current level of sensitivity, are not of great use in contributing to the evaluation of cases of suspected toxoplasmic lymphadenitis, which continues to be best diagnosed by accurate histopathologic examination. PMID- 1740300 TI - Primary (granulomatous) angiitis of the central nervous system: a clinicopathologic analysis of 15 new cases and a review of the literature. AB - The clinical and pathologic features of 15 new cases of the uncommon primary or granulomatous angiitis of the central nervous system (PACNS) are described. To date, only 108 such cases have been reported in the English literature. Clinically, most PACNS patients have been young or middle-aged (mean age, 45 years; range, 3 to 96 years), with men outnumbering women slightly by a ratio of 4 to 3. The most frequent presenting complaints are headache, weakness, and confusion; less common complaints are aphasia, dysphasia, nausea or vomiting, loss of memory, and seizure disorder. There is usually no evidence of a systemic disease; the erythrocyte sedimentation rate is almost invariably normal, and there are no diagnostic laboratory tests. The cerebral angiogram usually shows multifocal, segmental stenosis or irregularity of small and medium-sized leptomeningeal and intracranial blood vessels, often with a beading or aneurysmal appearance, and alterations in blood flow in the affected regions. Anatomically, the angiitis is focal and segmental in distribution. An isolated negative biopsy, therefore, does not rule out the disease. Histologically, PACNS may be granulomatous, necrotizing, or lymphocytic in character, and mixed morphologic types often occur. Large- and small-vessel thrombosis is common. Acute lesions frequently coexist with healing or healed lesions. Involvement of extracranial blood vessels occurs only rarely. Past or current herpes zoster infection and Hodgkin's lymphoma are the most noteworthy clinical associations of PACNS, but whether they are causally related remains uncertain. PMID- 1740301 TI - Antigenic phenotypes of hairy cell leukemia and monocytoid B-cell lymphoma: an immunohistochemical evaluation of 66 cases. AB - Using a large panel of antibodies on multi-tumor block sections of routinely processed, paraffin-embedded fixed tissue, we compared the antigenic phenotype of 42 clinically, morphologically, and immunologically well-characterized cases of hairy cell leukemia (HCL) with 24 cases of monocytoid B-cell lymphoma (MBCL) selected from the Monocytoid B-Cell Lymphoma Registry at the City of Hope National Medical Center. The predominant antigenic phenotype of hairy cells was CD45 (leukocyte common antigen)+, CD45Ra (4KB5, MB1, MT2)+, L26+, CDw75 (LN1)+, CD74 (LN2)+, LN3+, MB2+, CD45RO (UCHL1)-, MT1-, CD15 (Leu-M1)-, neuron-specific enolase (NSE)-, epithelial membrane antigen-, and CD30 (Ber-H2)-. The immunophenotype of neoplastic monocytoid B lymphocytes was essentially identical to that of the hairy cells, with one exception: the neoplastic monocytoid B lymphocytes were stained by epithelial membrane antigen in seven cases. An interesting observation was the staining by anti-muscle-specific actin of the neoplastic cells of MBCL in 53% of cases, but of none of the cases of HCL. The results of our study (1) indicate that HCL and MBCL can be immunophenotyped reliably on fixed tissue samples, (2) further confirm the proposed lineage relationship between these two lymphoproliferative disorders, and (3) indicate that decalcification of bone marrow biopsies does not adversely affect the immunoreactivity of hematopoietic-associated antigens. PMID- 1740302 TI - Autopsy analysis in patients with vascular diseases. AB - An analysis of autopsy findings in 68 patients who died with vascular surgical disorders was performed. Incorrect diagnoses and therapy were evaluated. It was found that complications of the primary disease or its treatment were frequently missed clinically (41%). Septic complications and severe hemorrhage were common in examinations of morbidity and mortality. In 13% of cases a treatment error with adverse impact on survival was detected. It is concluded that postmortem examination is a valuable tool in the final evaluation of patient care in a vascular surgical unit. A repeated plea for the autopsy is supported by this study. PMID- 1740303 TI - Herpes simplex virus hepatitis in pregnancy: a clinicopathologic study of three cases. AB - Herpes simplex virus (HSV) hepatitis is rare in adults, usually occurring in immunocompromised individuals and in otherwise healthy women in the third trimester of pregnancy. Three cases of HSV hepatitis occurring in pregnant women were diagnosed at our institution between 1981 and 1990. This diagnosis was not suspected clinically, and in each case was made on the basis of histology, immunoperoxidase studies, and viral cultures of liver tissue. Clinically, the patients had severe anicteric liver failure with markedly elevated serum aspartate aminotransferase and alanine aminotransferase levels; two of the three patients died. None had mucocutaneous lesions at the time of diagnosis. Histologically, two distinct patterns of necrosis and inflammation were seen. Two of the cases had well-demarcated foci of necrosis scattered randomly throughout the lobules with neutrophilic infiltration, giving the impression of abscess formation. Hepatocytes at the periphery of these areas of necrosis had enlarged nuclei with "ground-glass" inclusions; however, no Cowdry type A inclusions were seen. Rare multinucleated cells were present. Immunoperoxidase staining using antibodies to HSV was positive primarily in the hepatocytes with inclusions. The third case had diffuse, almost total hepatic necrosis with no viral inclusions and virtually no inflammatory response. This histologic pattern is similar to that seen in neonates with HSV infection. Immunoperoxidase studies in this case were negative; however, viral cultures were positive. While HSV hepatitis may be suspected or diagnosed on the basis of histology alone, viral cultures are an important adjunct since viral inclusions may be absent. Prompt diagnosis is important since antiviral therapy is now available. PMID- 1740304 TI - Primary pulmonary hypertension and human immunodeficiency virus infection in a non-hemophiliac man. AB - We describe clinical and postmortem findings in a 44-year-old man with pulmonary hypertension and infection with the human immunodeficiency virus (HIV-1). Plexogenic angiopathy and veno-occlusive lesions were present, in addition to a mild, patchy pulmonary interstitial lymphoid infiltrate. The clinical data for 14 previously reported cases of HIV-associated primary pulmonary hypertension are summarized. We speculate that these vascular changes may be due to damage from a specific immune response to HIV. PMID- 1740305 TI - Necrobiotic xanthogranuloma with myocardial lesions and nodular transformation of the liver. AB - A 73-year-old woman with a history of necrobiotic xanthogranuloma (NXG) with paraproteinemia died suddenly while hospitalized for bronchitis and congestive heart failure. At postmortem examination, myocardial lesions histologically typical of NXG were found. This is the fifth reported autopsy of a patient with NXG. In all five autopsied cases, and in two additional surgical cases, necrobiotic granulomas of internal viscera were present, and in three cases the myocardium was involved. In addition, our patient had nodular transformation of the liver, a rare lesion that was also reported in one of the previous autopsy cases with NXG. PMID- 1740306 TI - Peripheral biphasic adenocarcinoma of the lung: light microscopic and immunohistochemical findings. AB - We report two cases of peripheral biphasic adenocarcinoma primary in the lung. To our knowledge, peripheral adenocarcinoma of the lung with a spindle-cell component has not been described previously. Diffuse positive cytokeratin and negative vimentin immunostaining of the spindle-cell components support an epithelial differentiation of the malignant spindle cells. Although study of additional cases is needed, our initial findings suggest that immunohistochemical staining pattern may help distinguish these neoplasms from other biphasic neoplasms primary or secondary to the lung, such as carcinosarcoma or malignant mesothelioma. PMID- 1740308 TI - Identification of titanium in human tissues. PMID- 1740307 TI - Ossifying fibromyxoid tumor of soft parts: evidence supporting Schwann cell origin. AB - Immunohistochemical and ultrastructural studies of an ossifying fibromyxoid tumor of soft parts have been performed. Immunoreactivity of neoplastic cells for S-100 protein and glial fibrillary acidic protein, lack of immunoreactivity for type II collagen, and presence of basal lamina indicate that the tumor is of Schwann cell and not cartilaginous origin. PMID- 1740309 TI - Identification of titanium in human tissues. PMID- 1740310 TI - The fates of the new properties: intellectual workproducts. PMID- 1740311 TI - Quality control methods for data entry in pathology using a computerized data management system based on an extended data dictionary. AB - In pathology, computerized data management systems have been used increasingly to facilitate a more efficient supply of information. Since data entry precedes data utilization, the reliability of the information stored strongly depends on the quality of data input. Despite its potential capability, most personal computer based database software does not provide versatile and user-friendly data validation procedures. Therefore, we developed a data dictionary-driven data management system that enables the user to perform extensive validation routines without the need for hard programming. Using examples from an existing database for endometrial carcinomas, different types of data errors and their error traps are explained. It is pointed out that data type definitions, defaults, templates, or picture clauses are suitable means to avoid formal errors. Validations on data domains and ranges test whether data fall into a predefined scope. Relational checks control data validity within a context of different data items, whereas process routines provide automatic data computation, thereby circumventing user input. By exploiting the facilities of an extended data dictionary, a powerful tool is made available to secure various aspects of data integrity simultaneously with input. In this way, computerized data quality control can improve the efficiency and reliability of data management tasks in pathology. PMID- 1740312 TI - Cytogenetics of human oocytes, zygotes, and embryos after in vitro fertilization. AB - Chromosome errors, inherited or arising de novo during gametogenesis and transmitted at fertilization to the conceptus, may be a major cause of embryonic mortality. The in vitro fertilization and embryo transfer (IVF/ET) procedure provides extra material--oocytes, zygotes, and embryos--to investigate the contribution of chromosomal abnormality to implantation failure. This paper reviews the results of cytogenetic studies on such material. Estimates from a total of 1120 oocytes from 11 studies give an overall proportion of chromosomal abnormality of 35%. Single and multiple nullisomies and disomies are found, involving nonrandom chromosome gain or loss. Hypohaploid complements are more frequent than hyperhaploid complements. The higher rate of chromosome loss of hypohaploid karyotypes was found to be largely artifactual. The estimated overall frequency of aneuploidy is 13%. In embryos the level of chromosomal abnormality is 23%-40%. Errors of fertilization are responsible for a substantial number of triploid embryos, many of which develop into mosaics. Factors extrinsic to the conceptus, such as infertility, advanced maternal age, and ovarian hyperstimulation, may increase the level of chromosomal abnormality. More refined methods for accurately recognizing and selecting chromosomally normal embryos for transfer are needed to improve the success rate of this reproductive technology. PMID- 1740313 TI - Maternal origin of deletion 15q11-13 in 25/25 cases of Angelman syndrome. AB - About half of the cases of Angelman syndrome arise from deletions of chromosome band 15q12. In 25 cases we have been able to determine the parental origin of the deletion and, in line with other reported cases, we have found the deletion to be of maternal origin. There were no exceptions. The parental origin was determined using cytogenetic markers in 13 of the cases, in nine by using the pattern of inheritance of restriction fragment length polymorphisms, and in three using both techniques. PMID- 1740314 TI - Molecular analysis of aberrations of Xp and Yq. AB - Three cases of Y chromosomal aberrations were studied using a panel of Y-specific DNA sequences from both Yp and euchromatic Yq. One case was a phenotypic male fetus with a Y-derived marker chromosome. The short arm of this chromosome was intact, but most of its long arm was missing. The second case had a 46,XYq- karyotype with portions of euchromatic Yq, including the spermatogenesis region, missing. The third case was a phenotypic female with a 46,XXp+ karyotype. The extra material on the Xp+ chromosome was derived from the heterochromatic, and part of the euchromatic, portion of Yq. Application of X-specific DNA sequences demonstrated that the distal portion of the short arm of the translocation X chromosome was deleted (Xpter-p22.3). The three examples demonstrate the importance of diagnostic DNA analysis in cases of marker chromosomes, and X and Y chromosomal aberrations. In addition, the findings in the patients facilitate further deletion mapping of euchromatic Yq. PMID- 1740315 TI - Influence of HLA genotype on birth weight of patients with Turner syndrome. AB - Growth failure starting before birth is a common characteristic in Turner syndrome, and its pathogenesis is still not completely explained. Experiments performed in mice and rats to test whether a genetic disparity between mothers and offspring and maternal immunological status have any influence on litter size have demonstrated that allogenic litters are significantly larger in size than genetically compatible ones. Studies in humans have given contrasting results, but some authors have found that heterozygosity at enzyme loci and in blood groups is positively correlated with intrauterine growth. HLA class I and II polymorphisms were defined in 53 patients with Turner syndrome and in their parents, and lymphocytotoxic antibody detection was performed in 36 mothers. These data were related to the patients' birth weight. The frequency of the HLA B16 allele in patients with a birth weight greater than 10th centile was significantly higher in comparison with those less than 10th centile. HLA antigen sharing was present in 43 couples (81.1%). Mean birth weight was 2934 +/- 472 g in patients without HLA antigen parental sharing and 2721 +/- 529 g in those whose parents shared HLA antigens. The mean birth weight of the 10 patients whose parents do not share HLA antigens was significantly higher than that of the patients with parental HLA-B+ DR sharing (P less than 0.05) and not significantly highe than in those patients with parental HLA sharing at other HLA loci. Patients whose parents shared B+DR antigens also had significantly smaller birth weights than those with B and A+B+DR sharing (P less than 0.025 and P less than 0.025). No significant difference in mean birth weight was found in relation to other parameters, such as mother-child histocompatibility, HLA homozygosity and lymphocytotoxic production in the mothers. PMID- 1740316 TI - Cytogenetic and molecular characterization of marker chromosomes in patients with mosaic 45,X karyotypes. AB - Cytogenetic and molecular techniques were employed to determine the origin of marker chromosomes in five patients with mosaic 45,X karyotypes. The markers were shown to be derived from the X chromosome in three female patients and from the Y chromosome in one female and one male. One of the female patients, with a very small, X-derived ring chromosome, had additional phenotypic abnormalities not typically associated with Turner syndrome. In this patient, both the ring and the normal X chromosomes replicated early; perhaps the unusual phenotype is the result of both chromosomes remaining transcriptionally active. These studies illustrate the power of resolution and utility of combined cytogenetic and molecular approaches to some clinical cases. PMID- 1740317 TI - Molecular characterization of beta-thalassemia in Czechoslovakia. AB - We have identified different beta-thalassemia mutations in 93 members of 34 families of Czech or Slovakian descent using gene amplification, hybridization with specific 32P-labeled oligonucleotide probes, sequencing of amplified DNA, and gene mapping. The G----A mutation at IVS-I-1 was found in 18 families; other Mediterranean mutations were IVS-II-1 (G----A), IVS-II-745 (C----G), IVS-I-110 (G ---A), and codon 39 (C----T); these were present in 9 additional families. The G- --T mutation at codon 121, known to cause Heinz-body beta-thalassemia, was present in 3 families, and the frameshift at codons 82/83 (-G), first described in the Azerbaijanian population, in 2 families. A newly discovered allele was a frameshift at codons 38/39 (-C). One beta-thalassemia allele was incompletely characterized. We observed in 2 families a T----C mutation at position +96 UTR (untranslated region) relative to the termination codon; this mutation likely is a rare polymorphism. alpha-Thalassemia was rare; only one person carried the alpha 3.7 heterozygosity, and one other had a yet to be identified alpha thalassemia-1, while seven had the alpha alpha alpha anti 3.7 triplication. PMID- 1740318 TI - The role of the sex-determining region of the Y chromosome (SRY) in the etiology of 46,XX true hermaphroditism. AB - The syndrome of 46,XX true hermaphroditism is a clinical condition in which both ovarian and testicular tissue are found in one individual. Both Mullerian and Wolffian structures are usually present, and external genitalia are often ambiguous. Two alternative mechanisms have been proposed to explain the development of testicular tissue in these subjects: (1) translocation of chromosomal material encoding the testicular determination factor (TDF) from the Y to the X chromosome or to an autosome, or (2) an autosomal dominant mutation that permits testicular determination in the absence of TDF. We have investigated five subjects with 46,XX true hermaphroditism. Four individuals had a normal 46,XX karyotype; one subject (307) had an apparent terminal deletion of the short arm of one X chromosome. Genomic DNA was isolated from these individuals and subjected to Southern blot analysis. Only subject 307 had Y chromosomal sequences that included the pseudoautosomal boundary, SRY (sex-determining region of Y), ZFY (Y gene encoding a zinc finger protein), and DXYS5 (an anonymous locus on the distal short arm of Y) but lacked sequences for DYZ5 (proximal short arm of Y) and for the long arm probes DYZ1 and DYZ2. The genomic DNA of the other four subjects lacked detectable Y chromosomal sequences when assayed either by Southern blotting or after polymerase chain reaction amplification. Our data demonstrate that 46,XX true hermaphroditism is a genetically heterogeneous condition, some subjects having TDF sequences but most not. The 46,XX subjects without SRY may have a mutation of an autosomal gene that permits testicular determination in the absence of TDF. PMID- 1740319 TI - Identification of factor IX mutations in haemophilia B: application of polymerase chain reaction and single strand conformation analysis. AB - The molecular characterization of two haemophilia B defects, Calgary 1 and Calgary 2, was carried out using polymerase chain reaction (PCR) amplification and direct dideoxy sequencing. It had been previously shown that the Calgary 1 mutation affects the 5' TaqI restriction site of exon VIII, whereas Calgary 2 involves the loss of the 3' TaqI site of exon VIII of the factor IX gene. Sequencing data has now revealed that each of these alterations involves a C-to-T transition within a CpG dinucleotide. In each instance an arginine residue is replaced by a stop codon. These cases represent the recurrence of each particular alteration, both of which are predicted to result in the production of a truncated protein lacking a significant part of the catalytic region. A recently developed technique that reveals base substitutions as single-strand conformation polymorphisms (SSCP) was adapted for modelling in the detection of point mutations. Referred to here as single-strand conformation (SSC) analysis, this procedure, used in association with PCR, provided a reliable and sensitive system for molecular diagnosis in each of the cases presented. Computer-generated secondary structure predictions demonstrated a strong correlation with experimental results and the technique was used to screen 11 additional patients in the same region. A change detected by SSC analysis in one patient was localized to 55 base pairs, sequenced, and identified as a conservative amino acid substitution. This patient is now referred to as Calgary 3. PMID- 1740320 TI - Chromosome 1 in human colorectal tumors. Cytogenetic research on structural changes and their significance. AB - The significance of short and long arm anomalies of chromosome 1 was investigated in 55 colorectal tumors comprising 41 carcinomas and 14 adenomas. The tumors were at various stages of transformation from adenoma to carcinoma. Our investigation was prompted by the observation of a p32-pter deletion on the short arm of chromosome 1 in a case of benign tubulovillous adenoma with mild dysplasia, as well as by frequent reports that chromosome 1 is involved in many neoplastic processes. Long arm anomalies were found in seven of the 41 carcinomas, six of which were in stage B2, and short arm anomalies in ten carcinomas at various stages. Three of the adenomas exhibited chromosome 1 anomalies, which in one case comprised a 1p32-pter deletion only. Overall, short arm anomalies especially concerned the p32-36 region. These results suggest that the cytogenetic anomalies respectively located on the short and long arms of chromosome 1 should be considered separately. Damage to the long arm might constitute a late non specific event, whereas damage to the p32-pter region of the short arm might be involved in triggering colorectal tumor development. PMID- 1740321 TI - Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations. AB - We have examined the associations between levels of plasma apolipoprotein (apo) AI, apo CIII and apo AIV and genetic variation in the apo AI-CIII-AIV gene cluster in 162 boys and young men from Belgium aged from 7 to 23 years. Genotypes were determined for six restriction enzymes XmnI, PstI, SstI, PvuIIA-CIII, PvuIIB AIV and XbaI, and for the G to A substitution at -75 bp in the 5' region of the apo AI gene. The polymorphism most strongly associated with apo AI levels was the G to A substitution (P = 0.025, R2 x 100 = 3.6%) confirming previous observations. The polymorphism most strongly associated with apo CIII levels was that of PvuIIA-CIII (P = 0.023, R2 x 100 = 2.9%) in the apo CIII gene. This novel association must be interpreted with caution until it has been confirmed in an independent sample. The polymorphism associated with the largest effect on apo AIV levels was that detected with XbaI in the apo AIV gene, but this association was not statistically significant. Previously reported associations between the SstI polymorphism and triglyceride levels, and between the PstI polymorphism and apo AI levels, were weakly detected in the present sample. Our results show that variation associated with some of the polymorphisms in the apo AI-CIII-AIV cluster makes a small, but statistically significant, contribution to the determination of apo AI and apo CIII levels in this sample of young men and boys. These observations may, in part, explain reported associations between polymorphisms in this gene cluster, differences in plasma lipid and lipoprotein levels, and prevalence of coronary artery disease. PMID- 1740322 TI - Sperm chromosome complements from two human reciprocal translocation heterozygotes. AB - Using the hamster oocyte/human sperm fusion technique, we studied sperm chromosome complements in two male reciprocal translocation heterozygotes, 46,XY,t(11;17)(p11.2;q12.3) and 46,XY,t(1;11) (p36.3;q13.1). For the t(11;17) carrier, 202 sperm chromosome complements were obtained, but 18 karyotypes were not included in the segregation data because of multiple breaks and rearrangements. The alternate and adjacent I types, adjacent II, and 3:1 segregations accounted for 38.6%, 32.1%, 26.6%, and 2.7% of the sperm analyzed from the t(11;17) carrier. A total of 575 sperm chromosome complements was obtained using sperm from the t(1;11) heterozygote, and 27 karyotypes were excluded from the segregation data because of multiple breaks and rearrangements. For the t(1;11) carrier, the alternate and adjacent I types, adjacent II, and 3:1 segregations were responsible for 31.4%, 42.9%, 15.9%, and 8.0% of the analyzed sperm chromosome complements. Chromosomal abnormalities unrelated to the translocation, particularly the conservative estimate of aneuploidy frequency, were within the range observed in normal men. Hence, there was no evidence for an interchromosomal effect causing meiotic nondisjunction, despite the large sample sizes studied. PMID- 1740323 TI - Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction. AB - Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA. PMID- 1740324 TI - Transferrin subtypes in 51 Danish patients with hereditary haemochromatosis and in 847 normal subjects. AB - Transferrin (TF) subtypes were determined by isoelectric focusing in 51 unrelated Danish patients with hereditary haemochromatosis (HH) and in 847 normal subjects. The following TF phenotype frequencies were observed in HH patients and controls, respectively: TF*C1, 70.6% vs. 58.8%; TF*C2, 5.9% vs. 2.4%; TF*C3, 0% vs. 0.4%; TF*C1-2, 11.8% vs. 24.7%; TF*C1-3, 5.9% vs. 9.7%; TF*C2-3, 3.9% vs. 2.2%; TF*B C1, 2.0% vs. 1.5%; TF*B-C2, 0% vs. 0.4%. None of these differences were statistically significant. There was no relationship between the TF subtypes and the clinical or paraclinical expression of disease in HH patients. PMID- 1740325 TI - A possible mosaic form of delayed centromere separation and aneuploidy. AB - On average, a "normal" centromere separation sequence was seen in 3 neonates with trisomy 18 and in their parents. When evaluating individual mitoses, unusually late separating chromosomes 18 were found in a few cells of one of the parents in each family. A possible germline mosaicism of delayed separation in the parent may account for trisomy in the offspring. PMID- 1740326 TI - The unbalanced offspring of the male carriers of the 11q;22q translocation: nondisjunction at meiosis II in a balanced spermatocyte. AB - Carriers of the standard translocation t(11;22) (q23.3;q11.2) produce only one type of unbalanced offspring, a tertiary trisomy resulting into the karyotype 47,XX or XY, +der(22)t(11;22)(q23.3;q11.2), usually derived from the mother. The exception is one single patient 47,XY,t(11;22)(q23.3;q11.2), +der(22)t(11;22) (q23.3;q11.2)pat. We report a second case with the same karyotype, also of paternal origin. Thus, the rare unbalanced offspring of a carrier father (only 5 cases known) may receive a supernumerary der(22), as a consequence of tertiary trisomy, but also as a consequence of nondisjunction at meiosis II of a balanced spermatocyte. PMID- 1740327 TI - Further characterization of the new marker at DXS115 with regard to carrier detection in hemophilia A. PMID- 1740328 TI - A genetic linkage map of human chromosome 20 composed entirely of microsatellite markers. AB - Twenty-six (CA)n polymorphic microsatellites were isolated from a flow-sorted chromosome 20 library. To reduce the number of sequencing gels, these microsatellites were genotyped on 15 CEPH families using a procedure derived from the multiplex sequencing technique of G. M. Church and S. Kieffer-Higgins (1988, Science 240:185-188). A primary map with a strongly supported order was constructed with 15 (CA)n markers. Regional localizations for the 11 other microsatellites were obtained with regard to the primary map. The 26 loci span approximately 160 cM. Regional localizations for a set of index markers (D20S4, D20S6, D20S16, and D20S19) and for other markers from the CEPH Public Database (D20S5, D20S15, D20S17, and D20S18) have also been determined. The total map spans a genetic distance of approximately 195 cM extending from the (CA)n marker IP20M7 on 20p to D20S19 on 20q. The density of microsatellite markers is markedly higher in the pericentromeric region, with an average distance of 3 to 4 cM between adjacent markers over a distance of 43 cM. Two-thirds of these randomly isolated microsatellites are clustered in that region between D20S5 and D20S16 representing approximately one-fourth of the linkage map. This might suggest a nonrandom distribution of (CA)n simple sequence repeats on this chromosome. PMID- 1740329 TI - Genomic organization, nucleotide sequence, and cellular distribution of a Shaw related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. AB - Genomic and cDNA clones encoding a novel Shaw-related potassium channel gene have been isolated from mice and humans. The mouse-Kv3.3 gene encodes a protein of 679 amino acids. Unlike the vertebrate Shaker-related genes that have intronless coding regions, mouse Kv3.3 is encoded by at least two exons separated by 3 kb of intervening sequence. The amino-terminal 212 amino acids are encoded by a single exon, and the hydrophobic core of the protein beginning at the S1 transmembrane segment is contained in a separate exon. Multiple Kv3.3-hybridizing transcripts are visible in the mouse brain, liver, thymus, and heart. Using probes derived from a human genomic clone containing the 3' exon of human Kv3.3 (KCNC3), we have localized the gene to human chromosome 19. The related gene, human Kv3.4 (KCNC4), was localized to human chromosome 1. PMID- 1740330 TI - Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1). AB - Acid sphingomyelinase (ASM; HGMW-approved symbol, SMPD1) is the lysosomal phosphodiesterase that hydrolyzes sphingomyelin to ceramide and phosphocholine. The deficient activity of this enzyme results in Types A and B Niemann-Pick disease (NPD). The full-length cDNA encoding human ASM has been isolated and characterized (E. H. Schuchman, M. Suchi, T. Takahashi, K. Sandhoff, and R. J. Desnick (1991) J. Biol. Chem. 66:8531-8539), and the ASM gene has been localized to chromosomal region 11p15.1-p15.4 (L. V. Pereira, R. J. Desnick, D. Adler, C. M. Disteche, and E. H. Schuchman (1991) Genomics 9:229-234). Using the cDNA as a probe, a genomic clone containing the ASM genomic region was isolated and the complete nucleotide sequence of the human ASM gene, including 1116 and 468 nucleotides upstream and downstream from the ASM coding region, respectively, was determined. This housekeeping gene contained six exons ranging in size from 77 to 773 bp and five introns ranging in size from 153 to 1059 bp. Exon 2 was unusually large and encoded 258 amino acids, or about 44% of the mature ASM polypeptide. The alternatively spliced 172-bp type 1-specific sequence was encoded by exon 3, whereas the type 2-specific sequence was located at the 5' end of intron 2. An analysis of the intron/exon junctions revealed that there was a weak donor splice site (AAA gtgagg) at the exon 3/intron 3 junction which occasionally leads to alternative splicing of exon 3 and the occurrence of the type 2 and 3 ASM transcripts. A single Alu1 element in the reverse orientation was in intron 2, immediately downstream from the type 2-specific sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740331 TI - Generation of a panel of somatic cell hybrids containing fragments of human chromosome 12P by X-ray irradiation and cell fusion. AB - We have employed an irradiation and fusion procedure to generate somatic cell hybrids containing various fragments of the short arm of human chromosome 12 using a 12p-only hybrid (M28) as starting material. For the initial identification of hybrids retaining human DNA, nonradioactive in situ hybridization was performed. Seventeen cell lines appeared to contain detectable amounts of human material. Detailed characterization of these hybrids by Southern blot analysis and chromosomal in situ suppression hybridization (chromosome painting), using hybrid DNAs as probes after Alu element-mediated PCR, resulted in a hybrid panel encompassing the entire chromosome 12p arm. This panel will provide a valuable resource for the rapid isolation of region-specific DNA markers. In addition, this panel may be useful for the characterization of chromosome 12 aberrations in, e.g., human germ cell tumors. PMID- 1740332 TI - Mapping of the gene family for human heat-shock protein 90 alpha to chromosomes 1, 4, 11, and 14. AB - The HSP90 family of heat-shock proteins (encoded by genes for HSP90 alpha and beta) constitutes one of the major groups of proteins that are synthesized at increased rates in response to heat and other forms of stress. We previously isolated two distinct cDNA clones for HSP90 alpha from human peripheral blood lymphocytes and from HeLa cells transfected with the adenovirus E1A gene, respectively. To determine the organization of this complex multigene family in the human genome, we used three complementary approaches: Southern analysis of a panel of human/hamster somatic cell hybrids, molecular cloning of the cosmid HSP90 alpha clones from libraries prepared with DNAs from human lymphoblastoid cells, and in situ hybridization to human chromosomes. We demonstrate here that nucleotide sequences that encode HSP90 alpha map to human chromosomes 1q21.2-q22, 4q35, 11p14.1-p14.2, and 14q32.3. The chromosomal mapping of the loci, HSPCAL1, HSPCAL2, HSPCAL3, HSPCAL4, and the characterization of the respective genes should facilitate clarification of the organization of this gene family and lead to a better understanding of the biological functions of the gene product. PMID- 1740333 TI - Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. AB - Trimeric and tetrameric short tandem repeats (STRs) represent a rich source of highly polymorphic markers in the human genome that may be studied with the polymerase chain reaction (PCR). We report the analysis of a multilocus genotype survey of 97-380 chromosomes in U.S. Black, White, Mexican-American, and Asian populations at five STR loci located on chromosomes 1, 4, 11, and X. The heterozygote frequencies of the loci ranged from 0.36 to 0.91 and the number of alleles from 6 to 20 for the 20 population and locus combinations. Relative allele frequencies exhibited differences between populations and unimodal, bimodal, and complex distributions. Although deviations were noted at some locus population test combinations, genotype data from the loci were consistent overall with Hardy-Weinberg equilibrium by three tests. Population subheterogeneity within each ethnic group was not detected by two additional tests. No mutations were detected in a total of 860 meioses for two loci studied in the CEPH kindreds and five loci studied in other families. An indirect estimate of the mutation rates gave values from 2.3 x 10(-5) to 15.9 x 10(-5) for the five loci. Higher mutation rates appear to be associated with greater numbers of tandem repeats in the core motif. The most frequent genotype for all five loci combined appears to have a frequency of 7.59 x 10(-4). Together, these results suggest that trimeric and tetrameric STR loci are useful markers for the study of new mutations and genetic linkage analysis and for application to personal identification in the medical and forensic sciences. PMID- 1740334 TI - High-resolution localization of 69 potential human zinc finger protein genes: a number are clustered. AB - In this study, we describe the identification and partial characterization of 101 potential human zinc finger protein genes (ZnFPs). These sequences were isolated by hybridization of cosmids, obtained from mouse-human cell lines enriched for chromosome 11p, with an oligonucleotide specific for the "link" sequence between contiguous zinc fingers. Sixty-nine of these cosmids were regionally localized to human prometaphase chromosomes by in situ hybridization. The localization of these cosmids suggests that a number of finger protein genes occur in linked clusters. Their assignment to chromosomes 3p, 11p, 19p, 19qter, 20p, and 21q makes them valuable as markers or "candidate" genes for diseases associated with these chromosome regions. PMID- 1740335 TI - Distribution of moderately repetitive sequences pTR5 and LF1 in Xq24-q28 human DNA and their use in assembling YAC contigs. AB - Xq24-q28 DNA, from a hamster/human hybrid cell containing only that portion of the human X chromosome, was found to contain 56 TaqI restriction fragments that hybridized to the moderately repetitive sequence pTR5. Using the pTR5 sequence as a probe in colony hybridization, 136 cognate yeast artificial chromosome (YAC) clones were detected among a collection of 820 containing about three genomic equivalents of the Xq24-q28 DNA. The YACs were then grouped into 48 contigs and single clones containing one or more of the TaqI fragments. Overlaps were confirmed both by fingerprinting YACs with AluI and L1 probes and by additional information. A less complete analysis was also carried out with a second moderately repetitive sequence, LF1, and some smaller contigs were merged into larger ones. Moderately repetitive sequences can thus be used as probes for multiple loci in single hybridization experiments and can help to organize and confirm YAC overlaps during the development of maps with long-range contiguity. PMID- 1740336 TI - Structure and sequence of the human alpha-L-fucosidase gene and pseudogene. AB - Fucosidosis is a rare lysosomal storage disease resulting from a nearly complete deficiency of alpha-L-fucosidase enzyme activity. Previously, cDNA encoding human fucosidase was cloned and sequenced. Here we report the determination of the human fucosidase gene structure and sequence as well as the sequence of the fucosidase pseudogene. The gene encoding fucosidase is composed of eight exons spanning 23 kb of DNA. Analysis of the sequence 5' of the open reading frame indicates the presence of multiple transcription factor binding sites but no TATA box. Northern blot analysis has confirmed an mRNA size of 2.3 kb in human lymphoblasts, testis, and epithelial cells. We have also sequenced the processed pseudogene of fucosidase. The sequence of the pseudogene is 80% identical to that of fucosidase cDNA but does not contain an open reading frame. PMID- 1740337 TI - Variable (dG-dT)n.(dC-dA)n sequences in the porcine genome. AB - One of the more widely studied simple repeat sequences in the mammalian genome is the (dG-dT)n.(dC-dA)n dinucleotide repeat sequence. As these repeats are highly polymorphic and fairly evenly distributed in diverse mammalian genomes, they constitute a very powerful tool for genetic mapping in a wide variety of species. So far, the knowledge about repeat sequences in the porcine genome is sparse and only a few areas of this genome have been sequenced. We have isolated and characterized 108 porcine (dG-dT)n.(dC-dA)n sequences and studied the distribution of these, both by investigating random clones and by performing in situ hybridization. A remarkable correlation between humans and pigs was found with respect to the structure, to the number of repeat blocks, and to the chromosomal distribution. PMID- 1740338 TI - Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). AB - The human regulators of complement activation gene cluster (RCA cluster) have been partially characterized with yeast artificial chromosomes (YACs). While the data confirm many points previously elucidated, the finer resolution of YAC mapping has allowed the discovery and/or localization of partial gene duplications, the determination of gene orientations, and the measurement of gaps between known genes. Here nine overlapping YACs that encompass a genomic region of 800 kb, encoding four RCA genes and three gene-like elements, are described. The encoded genes and two of the gene-like elements share the same orientation and are ordered (5' to 3') DAF, CR2, CR1, MCP-like, CR1-like, and MCP. A C4bp like region lies upstream from DAF and is likely to correspond to one recently observed by F. Pardo-Manuel, J. Rey-Campos, A. Hillarp, B. Dahlback, and S. Rodriguez de Cordoba (1990, Proc. Natl. Acad. Sci. USA 87: 4529-4533). MCP-like, a new genetic element, was discovered and found to be homologous to the 5' portion of the MCP gene. Two large gaps of 85 kb (between CR2 and DAF) and 110 kb (between DAF and the C4bp-like element) could carry additional RCA genes. The arrangement of CR1, MCP-like, CR1-like, and MCP, in that order, strongly suggests that this region was generated by a single duplication of neighboring CR1/CR1 like and MCP/MCP-like forerunners. The RCA YACs will now serve as convenient DNA sources for the subcloning and further characterization of this region. PMID- 1740339 TI - Detecting single base substitutions as heteroduplex polymorphisms. AB - We have developed a sensitive technique for detecting single base substitutions in polymerase chain reaction (PCR) products from individuals heterozygous for polymorphisms or new mutations. This technique takes advantage of the formation of heteroduplexes in the PCR between different alleles from heterozygous individuals. These heteroduplexes can be detected on polyacrylamide gels because they migrate slower than their corresponding homoduplexes. Using PCR, we have generated a series of point mutations in a defined region of DNA in the equine infectious anemia virus (EIAV). Each mutation is the result of a single base substitution. By mixing the PCR products amplified from these mutations with one another, as well as with wildtype PCR products, we can generate heteroduplexes in which the identity of the mismatched bases is known. We detected eight of nine point mutations using this technique. We have also modified the electrophoretic conditions to optimize the detection of these heteroduplexes. In addition, the usefulness of this technique is demonstrated by its ability to detect a mutation in the cystic fibrosis gene that is the result of a single base substitution. This technique should prove useful for rapidly screening large numbers of individuals for new mutations or polymorphisms. PMID- 1740340 TI - PCR amplification of chromosome-specific DNA isolated from flow cytometry-sorted chromosomes. AB - We have established a method for amplifying and obtaining large quantities of chromosome-specific DNA by linker/adaptor ligation and polymerase chain reaction (PCR). Small quantities of DNA isolated from flow cytometry-sorted chromosomes 17 and 21 were digested with MboI, ligated to a linker/adaptor, and then subjected to 35 cycles of PCR. Using this procedure, 20 micrograms of chromosome-specific DNA can be obtained. Southern blot analysis using several DNA probes previously localized to chromosomes 17 and 21 indicated that these gene sequences were present in the amplified chromosome-specific DNA. A small quantity of the chromosome-specific DNA obtained from the first round of PCR amplification was used to amplify DNA for a second, third, and fourth round of PCR (30 cycles), and specific DNA sequences were still detectable. Fluorescence in situ hybridization using these chromosome-specific DNA probes clearly indicated the hybridization signals to the designated chromosomes. We showed that PCR-amplified chromosome 17 specific DNA can be used to detect nonrandom chromosomal translocation of t(15;17) in acute promyelocytic leukemia by fluorescence in situ hybridization. PMID- 1740341 TI - A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p. AB - A compound imperfect dinucleotide repeat element, [CA]4TTTGT[CT]7[CA]9AA[CA]4CCACATA[CA]3, was found approximately 10 kb 3' to the human glucokinase gene (GCK) from analysis of contiguous genomic DNA obtained from a bacteriophage lambda chromosome walk. Direct human genomic sequencing revealed the source of polymorphism to be variable numbers of CT and CA repeats. Altogether six alleles that range in length from +10 to -15 nucleotides compared to the most common (Z) allele have been identified. Alleles Z, Z + 2, and Z + 4 were present in American Blacks, Pima Indians, and Caucasians, with somewhat varied frequencies among the groups. Two alleles, Z + 10 and Z - 15, appear to be unique to American Blacks, while a Z + 6 allele was observed only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the CEPH reference pedigree collection is 44% and the PIC 0.44. The polymorphism is assayed by PCR amplification and resolution of 32P-end-labeled products (ranging in length from 180 to 205 bp) on denaturing polyacrylamide sequencing gels. Using the PCR assay, the human glucokinase gene was physically localized to chromosome 7 in a panel of rodent/human somatic cell lines. Genetic analysis in CEPH pedigrees placed the dinucleotide repeat element, and thereby the human glucokinase gene, on chromosome 7p between TCRG and a RFLP locus D7S57. The glucokinase dinucleotide repeat genetic marker can now be used to assess the role of the glucokinase gene in diabetes by population association studies. In addition, this repeat marker and others flanking it on chromosome 7 can be used in linkage studies with families segregating the disorder. PMID- 1740342 TI - A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci. AB - A new high-resolution genetic linkage map for human chromosome 7p has been constructed. The map is composed of 47 loci (54 polymorphic systems), 19 of which are uniquely placed with odds of at least 1000:1. Four genes are represented, including glucokinase (GCK, ATP:D-hexose-6-phosphotransferase, EC 2.7.1.2) which was mapped via a (CA)n dinucleotide repeat polymorphism. The sex-average map measures 94.4 cM and the male and female maps measure 73.2 and 116.1 cM, respectively. We believe that the genetic map extends nearly the full length of the short arm of chromosome 7 since a centromere marker has been incorporated, and the most distal marker, D7S21, has been cytogenetically localized by in situ hybridization to 7p22-pter. The average marker spacing is 2 cM, and the largest interval between uniquely placed markers is 13 cM (sex-average map). Overall, female recombination was observed to be about 1.5 times that of males, and a statistically significant sex-specific recombination frequency was found for a single interval. The map is based on genotypic data gathered from 40 CEPH reference pedigrees and was constructed using the CRI-MAP program package. The map presented here represents a combined and substantially expanded dataset compared to previously published chromosome 7 maps, and it will serve as a "baseline" genetic map that should prove useful for future efforts to develop a 1 cM map and for construction of a contiguous clone-based physical map for this chromosome. PMID- 1740343 TI - Genetic variability of the murine creatine kinase B gene locus and related pseudogenes in different inbred strains of mice. AB - The role of genetic variation in isoenzyme gene families is often poorly appreciated. We report here on the determination of DNA sequences and typing of genetic variability in four creatine kinase B (CKB) gene loci in different inbred strains of mice. The unique functional murine CKB gene was found to be nearly identical to the previously characterised rat and human sequences in both size and exon-intron structure. In this gene, approximately 0.5% allelic nucleotide positions as well as the lengths of simple A-rich and [TG]n repetitive elements located at the 5' and 3' sides of the transcribed segment, differed between inbred strains of mice. Preliminary experiments suggest that this sequence divergence is of importance for design of gene targeting strategies involving homologous DNA recombination. The three additional CKB-like gene loci in mice all had the characteristics of processed pseudogenes. By Southern blot analysis we could demonstrate that both the type and number of pseudogenes differed between inbred strains. Analysis of the CKB gene sequences enabled us to speculate about the evolutionary history of this highly polymorphic subfamily of genes. PMID- 1740344 TI - Assignment of rat linkage group V to chromosome 19 by single-strand conformation polymorphism analysis of somatic cell hybrids. AB - The rat provides a number of important models of human genetic disease; however, the rat genetic map has not been extensively developed. Although most rat chromosomes carry several gene assignments, some major linkage groups (LG) remain to be mapped. To determine the chromosome location of the largest unmapped linkage group in the rat (LG V containing multiple carboxylesterase loci), we used single-strand conformation polymorphism analysis to identify the rat esterase-10 gene in a panel of rat x mouse somatic cell hybrids. We found that the carboxylesterase gene family and hence LG V are located on rat chromosome 19. We have also confirmed the assignment of the angiotensinogen gene to rat chromosome 19 and have used a large set of recombinant inbred strains to map two anonymous variable number of tandem repeat (VNTR) markers to this chromosome. The current findings bring the total number of genes assigned to rat chromosome 19 from 3 to 19 and provide further evidence of substantial homology between this chromosome and chromosome 8 in the mouse. PMID- 1740345 TI - Rps4 maps near the inactivation center on the mouse X chromosome. AB - RPS4Y, a Y-linked gene in humans, appears to encode an isoform of ribosomal protein S4. A homologous locus on the human X chromosome, RPS4X, lies close to the X-inactivation center but fails to undergo X-inactivation. We have isolated a genomic clone from the mouse Rps4 locus, the homolog of human RPS4X. We derived an intron probe that hybridizes to the functional Rps4 locus but does not cross hybridize to related sequences elsewhere in the mouse genome. Genetic mapping utilizing interspecific mouse backcrosses and the intron-specific probe demonstrates that Rps4 maps close to the Phka locus on the mouse X chromosome and in the vicinity of the X-inactivation center. The gene order Ccg-1-Rps4/Phka-Xist Pgk-1 is conserved between mouse and human. PMID- 1740346 TI - Use of Alu-PCR to characterize hybrids containing multiple fragments and to generate new Xp21.3-p22.2 markers. AB - Irradiation fragment hybrids potentially provide highly enriched sources of region-specific human DNA. However, such hybrids often contain multiple human pieces, not all of which can be easily detected. To develop specific resources for rapidly generating markers from Xp21.3-p22.2, we have single cell cloned two previously constructed irradiation hybrids that contain markers in this region and have achieved segregation of the different known fragments originally retained. Alu-PCR products were generated from subclones positive or negative for Xp21.3-p22.2 markers, and comparison of the ethidium bromide patterns between sister subclones facilitated identification of bands likely to map to particular regions; in contrast, subclones that shared markers but were derived from independent lines showed no overlap in ethidium bromide pattern. All Alu-PCR products from one subclone, 50K-19E, in which only three closely linked markers were detected (DXS41, DXS208, DXS274) were mapped back to their region of origin. Of 28 products, 15 mapped to Xp21.2-p22.2, and these make up a new set of regionally assigned markers. However, the mapping data identified four separate Xp fragments in 50K-19E, only one of which had been picked up by marker analysis. Mapping back gel-isolated Alu-PCR products from an irradiation hybrid prior to any cloning or screening generates a comprehensive profile of the human DNA retained and permits rapid selection of sequences derived only from the region of interest. PMID- 1740347 TI - Mapping of locus for X-linked congenital stationary night blindness (CSNB1) proximal to DXS7. AB - A recombinant chromosome in a male affected with X-linked congenital stationary night blindness (CSNB1) provides new information on the location of the CSNB1 locus. A four-generation family with five males affected with X-linked CSNB was analyzed with five polymorphic markers for four X-chromosome loci spanning the region OTC (Xp21.1) to DXS255 (Xp11.22). Four of the males inherited the same X chromosome; one male inherited a chromosome that from OTC to DXS7, inclusive, was derived from the normal X chromosome of his unaffected grandfather and that from a location between DXS7 and DXS426 proximally was derived from the chromosome carrying the CSNB1 locus. This recombinant maps the CSNB1 locus in this family to a region on the short arm of the X chromosome proximal to the DXS7 locus. PMID- 1740348 TI - Alkaline phosphatase activity is expressed only in B lymphocytes committed to proliferation. AB - Alkaline phosphatase (APase) activity was measured in murine splenic lymphocytes stimulated with the T lymphocyte mitogens phytohemagglutinin (PHA) and Concanavalin A (Con A) and the B lymphocyte mitogens lipopolysaccharide (LPS) and anti-immunoglobulin (anti-Ig). APase activity was found to be enhanced specifically in mitogen-stimulated B lymphocytes, but not in T lymphocytes. This enhancement starts around 8 h after stimulation with a mitogen. With soluble anti Ig it was observed that the B cells enter G1 phase as assessed by RNA synthesis and blast transformation. However, these cells fail to synthesize DNA and also do not show any increase in APase activity. When the same anti-Ig coupled to Sepharose was used as a stimulator, cells synthesized DNA and also showed significant increase in APase activity. When hydroxyurea was added, the enhancement in APase activity by the mitogen was not diminished although the cells failed to synthesize DNA. These observations indicate that APase activity is enhanced only in activated B cells committed to proliferation. PMID- 1740349 TI - Development of an antibody that binds sulfur mustard. AB - An antibody that binds bis(2-chloroethyl) sulfide (sulfur mustard) was developed. The immunizing antigen was prepared from the hapten 4-(2-chloroethyl)benzoic acid covalently bound to keyhole limpet hemocyanin (KLH). The antibody was monitored by a solid phase enzyme-linked immunosorbent assay (ELISA). The test antigen consisted of a second hapten, 8-chlorocaprylic acid, covalently bound to bovine serum albumin (BSA). The test antigen was absorbed to the wells of 96-well plates. The immunizing and test antigens contain a common chloroethyl moiety. Thiodiglycol, the principal hydrolysis product of sulfur mustard, does not react with the antibody. This antibody, because of its specificity, has the potential to be a valuable tool for mustard research and forensic detection. PMID- 1740350 TI - Association of recombinant soluble IL-6-signal transducer, gp130, with a complex of IL 6 and soluble IL-6 receptor, and establishment of an ELISA for soluble gp130. AB - IL-6 mediates its pleiotropic functions through two membrane proteins, a ligand binding molecule (IL-6 receptor, IL-6R) and a non-ligand-binding signal transducer (gp130). Starting with a previously isolated cDNA clone encoding human gp130, recombinant soluble gp130 (sgp130) lacking the transmembrane and cytoplasmic regions was expressed in COS7 cells or CHO cells. sgp130 could associate with a complex of IL-6 and soluble IL-6R (sIL-6R), also lacking transmembrane and cytoplasmic regions. This indicated that extracellular region of gp130 was responsible for the association with IL-6R which was occupied by IL 6. An enzyme-linked immunosorbent assay (ELISA) for the quantitation of sgp130 was established, which was based on the interaction of sgp130 with the complex of IL-6 and sIL-6R and could detect sgp130 as low as 1 ng/ml. PMID- 1740351 TI - Monoclonal antibodies against soman: characterization of soman stereoisomers. AB - Hybridomas were produced which expressed monoclonal anti-soman antibodies as determined by microtiter enzyme-linked-antibody immunoassay (EIA). Each of these antibodies was titrated using a competitive inhibition enzyme immunoassay (CIEIA) with a variety of test ligands. The ligands used included soman (a racemic mixture), sarin, tabun, and each of the four stereoisomers of soman (C+ P+, C+ P , C-P+ and C-P-). In all cases the antibodies tested exhibited IC50 values of 10( 4)-5 x 10(-6) M for soman. When sarin or tabun was used as a ligand, the antibodies exhibited no cross reactivity. All of the antibodies cross reacted with the four soman stereoisomers. A second group of hybridomas were produced which expressed monoclonal antibodies against CsPs-soman. These antibodies were used to make preliminary absolute chiral assignments to the four soman stereoisomers. PMID- 1740352 TI - Potentiation of the humoral response of intravenous antigen by splenotropic liposomes. AB - We have recently described that large liposomes composed of egg phosphatidylcholine (PC), cholesterol (chol) and monosialoganglioside GM1 show elevated accumulation in the red pulp of the spleen when they are i.v. administered into mice. Up to 50% of the injected dose was found in spleen at 4 h post injection. In this report, we have investigated the potential application of such liposomes in the stimulation of anti-lysozyme response in mice. Lysozyme entrapped in the splenotropic liposomes composed of PC/chol/GM1 showed higher efficiency in potentiating the humoral response than that of either free lysozyme or lysozyme entrapped in hepatotropic liposomes composed of PC/chol. The results demonstrate that high levels of i.v. antigen delivery by liposomes to the splenic macrophage instead of the liver Kupffer cells is important in the liposomal adjuvanticity. The antibody elicited by the liposome entrapped antigen was mainly IgG1 subtype. PMID- 1740353 TI - Perforin is expressed in CTL populations generated in vivo. AB - Immunization of C57BL/6 mice with syngeneic tumor cells, MBL-2, resulted in the generation of antitumor effector cells in vivo. The immunized C57BL/6 mice permanently rejected viable MBL-2 lymphoma cells, but not B16 melanoma cells. Cytotoxic T cells obtained from MBL-2-immunized mouse peritoneal cells (PEC) showed specific cytotoxicity against MBL-2, but not to YAC-1, RDM-4 and Meth A cells. By sorting with FACStar, the specific CTL were characterized as TCR alpha beta+ CD8+ T cells. Moreover, the cytoplasm of in vivo-induced CTL was stained with a monoclonal antibody against perforin. The localization of perforin in cytoplasmic granules of CTL was demonstrated by electron microscope analysis. This experiment presented the first evidence that in vivo-induced CD8+ CTL against syngeneic tumor cells expressed significant amounts of perforin. PMID- 1740354 TI - Specific functions of human NK cells. AB - Since natural killer (NK) cells lack both CD3/TCR molecules and surface Ig, it is generally thought that they are unable to recognize antigens. However, CD3-CD16+ cells were found to respond in MLC against irradiated allogeneic mononuclear cells and to lyse normal PHA blasts derived from the stimulating donor, but not autologous cells or cells derived from most allogeneic donors. A similar pattern was obtained with cloned NK cells, thus indicating that the ability to specifically recognize given normal allogeneic cells is a clonally distributed function. Moreover, analysis of NK clones for their ability to lyse either tumor cells or normal PHA blasts (both derived from individual cancer patients) indicated that the two phenomena are distinct. Analysis of a large number of NK clones derived from a given individual for their ability to lyse a panel of allogeneic donors allowed the identification of at least four groups of clones characterized by unique patterns of reactivity ("specificities"). We further studied the mode of inheritance of the various NK-defined specificities: all the characters "susceptibility to lysis" by NK clones (displaying one or another specificity) segregated independently, were inherited in an autosomic recessive manner and were carried by chromosome 6. The finding of clonally distributed specific functions in NK cells suggested the existence of clonally distributed receptor molecules. Along this line mAbs were raised against NK clones, and screened for their ability to trigger the immunizing clones: two mAbs (termed GL183 and EB6) were directed against a novel family of 58-kDa surface molecules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740355 TI - The effects of complement depletion on corneal inflammation in rats. AB - There are indications that complement activation may be involved in inflammatory processes of the cornea. To investigate the role of the complement system in experimental keratitis, rats were depleted of their plasma complement by treatment with cobra venom factor (CVF). intraperitoneal injection of CVF resulted in undetectable complement serum activity for 6 days when measured by a hemolytic assay. The corneal inflammatory response, induced by a single intracorneal injection of heterologous serum into nonsensitized CVF-treated rats, was suppressed significantly. The onset of the clinical symptoms of keratitis was delayed, and the severity was reduced. In addition, analysis of the serum antibody titers showed impaired antibody synthesis in the CVF-treated group. When keratitis was induced by an intracorneal antigen challenge in sensitized rats, no difference was observed when comparing the clinical signs of keratitis of CVF treated animals with sham-treated animals. In addition, CVF treatment did not alter the course of lipopolysaccharide (LPS)-induced corneal inflammation. These findings suggest that the role of plasma complement activation in antigen- and LPS-induced keratitis appears to be limited. The implications for the immunopathologic mechanisms underlying keratitis are discussed. PMID- 1740356 TI - Distributional change of fodrin in the wound healing process of the corneal epithelium. AB - Distribution of fodrin, F-actin, and E-cadherin in the wound healing process of the mouse corneal epithelium was examined by immunolabeling techniques. In the normal epithelium, fodrin, F-actin, and E-cadherin were observed only in the cell periphery. After wounding, however, fodrin was observed diffusely in the basal cell cytoplasm. Distribution of the other two proteins was not changed. Fodrin in the upper cell layers did not show cytoplasmic labeling. The distributional change of fodrin in the basal cell was seen not less than 1 mm apart from the wound edge and as early as 5 min after the wounding, lasted for about 12 hr, and then gradually disappeared. The change in fodrin localization is one of the earliest phenomena which occur in the corneal epithelium after wounding. Because fodrin is an actin-binding protein and is believed to interact with E-cadherin, this change may be important in modulating the cytoskeleton and the intercellular junction before cell migration occurs. PMID- 1740357 TI - The large-conductance potassium ion channel of rabbit corneal epithelium is blocked by quinidine. AB - Basal layers of the rabbit corneal epithelium contain a large-conductance potassium ion (K+) selective channel (160-170 pS in 150 mM KCl). This channel previously was shown to be blocked by cesium and barium ions applied to its outer surface. By direct patch clamp experiments, it is shown that the channel also is blocked by quinidine in the 0.1-1 mM range when applied either to the outside or inside of membrane patches containing these channels. This additional pharmacologic tool should aid in identifying the individual currents that compose the macroscopic currents from corneal epithelial cells and eventually should help to provide a detailed assessment of their function. PMID- 1740358 TI - Induction of corneal epithelial cytochrome P-450 arachidonate metabolism by contact lens wear. AB - Two biologically active cytochrome P-450 arachidonate metabolites previously were characterized: 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) and 12(R)-hydroxy-5,8,14-eicosatrienoic acid (12(R)-DH-HETE), which are endogenously formed in the corneal epithelium. The functional activity of these novel metabolites mimics changes observed in hypoxic corneas. Therefore, the effect of hypoxic stress was examined on metabolite formation in rabbits fitted with polymethylmethacrylate contact lenses. Although applied lenses fit tightly to the rabbit cornea, mechanical irritation also may contribute to the ocular response. Contact lens-induced hypoxic stress stimulated endogenous formation of both 12(R) HETE (a sodium, potassium adenosine triphosphatase inhibitor) and 12(R)-DH-HETE (a vasodilatory, chemotactic, and angiogenic factor) in a time-dependent manner. After 4 hr of contact lens wear, a 21-fold increase in endogenous 12(R)-HETE formation concomitant with an increase in corneal thickness was observed. After prolonged contact lens wear (144 hr), a 23-fold increase in endogenous 12(R)-DH HETE formation was found, corresponding with the appearance of a marked conjunctival inflammation characterized by corneal neovascularization. The increased formation of these compounds was associated with time-dependent changes in corneal endothelial morphology. The ability of 12(R)-HETE and 12(R)-DH-HETE to mediate the clinical signs of corneal hypoxia suggest these metabolites may be potential mediators of contact lens complications that followed conditions of hypoxic stress and possibly mechanical irritation in this model. PMID- 1740359 TI - Collagen shields as a vehicle for collecting and studying migratory cells on human corneas. AB - Collagen shields have been studied in the enhancement of the initial healing of epithelial defects, as an adjunct in the treatment of dry eye, and as a reservoir and delivery system for topical ocular medications. The authors used collagen shields to collect information on the numbers and types of free cells populating the normal and postoperative ocular surface. In addition, correlative microscopic techniques were used to study details of the mechanisms responsible for the dissolution of the shields when applied to the human eye. Collagen shields were applied as a bandage lens on the eyes of patients who underwent extracapsular cataract extraction (n = 10) or penetrating keratoplasty (n = 10) and on normal volunteers (n = 10). The shields were collected at the 1-day postoperative examination and fixed in aldehyde mixtures. Specimens then were processed for correlative light (LM), transmission (TEM), and scanning (SEM) microscopy. Cell accumulation was shown by SEM on both anterior and posterior shield surfaces. Cell adherence occurred primarily on the posterior shield periphery for approximately 2 mm, with the central zone relatively clean. Both LM and TEM evaluation revealed cell counts ranging from 0.066 cells/10(4) microns2 (standard deviation, +/- 0.256) in healthy eyes compared with shields placed on postoperative eyes (194.25 +/- 7.32 cells/10(4) microns2). Various correlative microscopy techniques revealed that most cells were polymorphonuclear leukocytes with a low number of other hematogenous (lymphocytes and monocytes) and exfoliated epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740360 TI - Adhesion complex formation after small keratectomy wounds in the cornea. AB - The adhesion complex of the corneal epithelium consists of the hemidesmosome and its associated structures, such as anchoring filaments, lamina densa of the basement membrane, and anchoring fibrils. It contributes to the adhesion of the corneal epithelium to Bowman's layer. To understand the adhesion complex better, an electron microscopic and immunofluorescence analysis was done of the reformation of the adhesion complex in small (1 mm) keratectomy wounds in the guinea pig cornea. In these wounds, the epithelium, hemidesmosomes, basal lamina, anchoring fibrils, and anterior stroma were removed. The wound bed was epithelialized completely by 24 hr after wounding. Immunofluorescence analyses involved the use of antibodies against plaque components of the hemidesmosome, an antibody against laminin, and an antibody against the collagen VII component of anchoring fibrils. At 18 hr after wounding, there was no morphologic evidence of hemidesmosomes at the epithelial-stromal interface. At 24 hr, hemidesmosomes were observed, with or without subjacent lamina densa. Furthermore, plaque components were detected by immunofluorescence in those cells in contact with the wound bed. In contrast, no type VII collagen was detected. On day 7, collagen VII, laminin, and bullous pemphigoid autoantibody markers colocalized along the wound bed as determined by immunofluorescence. However, at the ultrastructural level, even though the lamina densa of the basal lamina was observed primarily where hemidesmosomes were present, it remained incomplete. In this study, the precise temporal sequence in which components are incorporated into the assembling adhesion complex was described during wound healing. Furthermore, the possibility that the hemidesmosomal plaque nucleates the formation of the underlying basal lamina was discussed. PMID- 1740361 TI - Reduced epithelial adhesion after extended contact lens wear correlates with reduced hemidesmosome density in cat cornea. AB - Reduced epithelial adhesion in cat corneas after continuous wear of thick hydrogel contact lenses has been reported previously. To investigate the mechanism(s) underlying this observed loss of epithelial adhesion further, the corneas of both eyes of cats that had worn low-oxygen-transmissible thick parallel-design hydrogel contact lenses only in one eye for 8-121 days were examined using both light and transmission electron microscopy (TEM). Contact lens wear induced many changes in the epithelium, including a decrease in the number of cell layers and appearance of cuboidal rather than columnar basal cell shapes. In addition, TEM revealed that the number of hemidesmosomes (HDs) per micrometer of basement membrane was reduced significantly after contact lens wear. Anchoring fibrils in lens-wearing corneas appeared normal, and the reduction in epithelial adhesion occurred without obvious epithelial edema. Decreased epithelial adhesion after contact lens wear appears to be directly related to the reduced numbers of HDs. Possible reasons for decreased HD density, such as loss of basal cell shape and chronic epithelial hypoxia after contact lens wear, are discussed. PMID- 1740362 TI - Embryonic corneal epithelial actin alters distribution in response to laminin. AB - In the current study, laser scanning confocal image analysis was used to investigate the actin distribution in whole-mount preparations of freshly isolated and cultured corneal epithelia. Actin staining defined the cell borders and microvilli of the periderm cells. The actin was prominent as an organized network at the interface between the basal and periderm cells and in the basal compartment of the basal cells (actin cortical mat) when isolated with the basal lamina (BL). In epithelia isolated without BL, the actin in the periderm cells and the network at the periderm-basal cell interface was the same as in epithelia isolated with BL. However, the actin in the basal compartment of the basal cells was localized in the cellular blebs that projected from the basal cell surface. Epithelia isolated without BL and cultured in the presence of laminin reorganized the actin cortical mat within 2 hours. However, epithelia isolated without BL and cultured without BL proteins continued to have basal cell projections, sometimes into the pores of the filter. Treatment of epithelia with 2 microM cytochalasin D prevented the reorganization of the actin by laminin. In conclusion, the use of confocal analysis increased our understanding of actin distribution in the epithelial sheets. These results confirmed and extended previous studies using electron microscopy to determine that corneal epithelial cells respond to extracellular matrix molecules by an actin-dependent mechanism. PMID- 1740363 TI - Functional loss in age-related Bruch's membrane change with choroidal perfusion defect. AB - During a prospective study of age-related macular degeneration, evidence of diffuse Bruch's membrane disease was sought using fluorescein angiographic evidence of a prolonged choroidal filling phase. Dark-adapted static perimetry was done on eight eyes with this angiographic sign and on six eyes with a similar number of drusen but no manifest choroidal perfusion abnormality. Scotopic threshold was measured using the Humphrey automated perimeter and fine matrix mapping. In eyes without delayed choroidal perfusion, no discrete areas of increased threshold were found compared with the background sensitivity. By contrast, in seven of the eight eyes with fluorescein angiographic evidence of prolonged choroidal filling, discrete areas of scotopic threshold elevation (up to 3.4 log units) were recorded; these corresponded closely to regions of choroidal perfusion abnormality. It was postulated that diffuse deposits of abnormal material might account for both the perfusion abnormality and functional loss by acting as a diffusion barrier between the choriocapillaris and the retinal pigment epithelium. PMID- 1740364 TI - Temporal expression of the transthyretin gene in the developing rat eye. AB - Transthyretin (TTR) is a 55-kilodalton tetrameric protein that plays an important role in the plasma transport of thyroxine and retinol. Plasma TTR is synthesized in the liver, but major sites of synthesis also have been described in the choroid plexus (CP) epithelium, the visceral yolk sac, and the eye. Recently, the retinal pigment epithelium (RPE) was identified as the specific site of TTR synthesis in the rat eye, and it was suggested that this established a functional homology between the RPE and the CP epithelium. In this study, the temporal pattern of TTR mRNA expression was investigated in the rat eye and brain during development (embryonic day 10 [e10]-postnatal day 7 [P7]) by in situ hybridization and quantitative densitometry. The TTR mRNA was present in abundance in the primordial CP before organogenesis (e10-12), but in the eye, TTR mRNA first was detected at considerably lower levels after organogenesis (e16) and only in a subset of RPE cells in the equatorial region. The relative abundance of TTR mRNA in RPE rose gradually until e21, but on the first day of life a surge was seen, followed by stabilization at adult levels by P7. These findings suggest that the requirement for TTR in CP and RPE, and possibly its function, may differ during development. The postnatal surge in RPE TTR message levels raises the possibility that transcription of the TTR gene in the newborn animal may be responsive to newly encountered environmental stimuli in the perinatal period, such as incident light. PMID- 1740365 TI - Interocular differences in macular pigment density. AB - Interocular differences in the optical density of macular pigment were examined. Foveal and parafoveal sensitivities to lights of 460 and 530 nm were measured by heterochromatic flicker photometry for both eyes of ten subjects. These two wavelengths represent the maximum and minimum absorbance for macular pigment. Taking the difference in log sensitivity to the 460 nm light for the fovea and parafovea, after normalizing with respect to 530 nm, yields a measurement of the optical density of the macular pigment. Consistent interocular differences in macular pigment density were found for only two subjects, and these differences were less than 0.1. Other subjects frequently showed significant interocular differences on a given day but showed no consistent differences over the course of many days. In general, the amount of macular pigment measured for one eye was found to be essentially the same as that for the other eye. When measurements were averaged for the two eyes of each subject, significant differences in macular pigment density among subjects were found. PMID- 1740366 TI - Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control. AB - Total retinal volumetric blood flow rate was measured in 12 normal subjects and 18 poorly controlled diabetic patients with background diabetic retinopathy. Maximum or center-line erythrocyte velocity (Vmax) was assessed by bidirectional laser Doppler velocimetry in four to five major retinal veins of one eye of each subject. Venous diameter (D) was measured from monochromatic fundus photographs. Total venous cross-section and measured total retinal volumetric blood flow in the diabetic patients were significantly larger than normal (P = 0.001 and P = 0.02, respectively). A positive linear correlation was found between Vmax and D in normal and diabetic eyes. Volumetric blood flow rate, Q, varied with D at a power of 2.87 in normal eyes. Total volumetric blood flow correlated with total venous cross-section. It was found that Q in the temporal retina was significantly larger than in the nasal retina in normal subjects (P = 0.0008) and diabetic patients (P = 0.0002). A significant difference in Q was observed between the superior and inferior retina in diabetic patients (P = 0.03) but not in normal subjects. The retinal vascular regulatory response to 100% oxygen breathing was reduced (P = 0.019) in diabetic patients and correlated with the level of background diabetic retinopathy. A close estimate of total volumetric blood flow may be obtained from blood flow measurement in one major retinal vein and the determination of total venous cross-section. This may be important for clinical studies in which measurements of all individual retinal veins may not be feasible. PMID- 1740367 TI - Xyloside-induced disruption of interphotoreceptor matrix proteoglycans results in retinal detachment. AB - Unique domains of the retinal interphotoreceptor matrix (IPM), termed cone matrix sheaths, are composed largely of chondroitin 6-sulfate proteoglycan in most higher mammalian species. Recent investigations suggest that cone matrix sheaths participate in the maintenance of normal retinal attachment. To investigate the potential functional roles of IPM proteoglycans further, the synthesis of cone matrix sheath chondroitin 6-sulfate proteoglycan was perturbed in vivo. Intravitreal injections of p-nitrophenyl-beta-D-xylopyranoside (xyloside), a sugar that inhibits chondroitin sulfate proteoglycan synthesis, were administered to Yucatan micropigs. Their eyes were examined funduscopically and electroretinographically. At selected times, the eyes were enucleated and examined histochemically and immunohistochemically with various probes directed against cone photoreceptor cells and cone matrix sheaths. The IPM was affected selectively after xyloside administration; no inner retinal pathology or dysfunction was detected morphologically or electroretinographically. The degree of xyloside-induced perturbation was dependent on the duration of xyloside exposure and dose. It was classified into three stages, based on morphologic and histochemical criteria. Although all three stages could be observed in a given retina, a single stage typically predominated, depending on the particular dosage regimen. The early stage was characterized by IPM disruption, as evidenced by disorganization of chondroitin 6-sulfate and peanut agglutinin (PNA)-binding glycoconjugates. Cone photoreceptor cell outer segment degeneration and markedly decreased chondroitin 6-sulfate immunoreactivity distinguished the middle stage. During the late stage, there was a near complete absence of both immunoreactive chondroitin 6-sulfate and PNA-binding glycoconjugates in the IPM. Shallow retinal detachments that appeared funduscopically as patches of retinal whitening frequently were observed after moderate durations of xyloside exposure; these progressed peripherally with continued xyloside exposure. Histologically, the areas of retinal whitening corresponded to regions in which cone matrix sheaths were split transversely (ie, in a plane perpendicular to the longitudinal axes of the photoreceptor cell outer segments) or were separated completely from cone outer segments. Similar effects were not observed in control eyes. These results suggest that adhesion between the neural retina and retinal pigmented epithelium may be dependent, in part, on continuous synthesis of cone matrix sheath associated proteoglycans and, potentially, other IPM proteoglycans. In addition, these proteoglycans appear to be necessary for the maintenance of cone photoreceptor cell outer segment integrity. PMID- 1740368 TI - Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat. AB - The blood-retinal barrier is part of the blood-ocular barrier. Retinal pigment epithelial cells connected by tight junctions serve as an outer blood-retinal barrier, and the nonfenestrated endothelial cells of blood vessels sealed by tight junctions serve as an inner blood-retinal barrier. Using antibodies specific for the erythrocyte/HepG2-type glucose transporter (GLUT1), one isoform of facilitated-diffusion glucose transporters, it was found, by ultrastructural cytochemical examination, that GLUT1 in the rat was localized at both the apical and basolateral plasma membranes of retinal pigment epithelial cells. The fenestrated endothelial cells of the underlying choriocapillaries were negative for GLUT1. In the inner retina, GLUT1 was found at both the luminal and contraluminal plasma membranes of endothelial cells. These observations show that GLUT1 is concentrated at the critical plasma membranes of the blood-retinal barrier and may serve as the machinery for glucose transport across the barrier. PMID- 1740369 TI - Ocular infection with a murine neurovirulent retrovirus does not cause retinal degeneration. AB - The developing eyes of CFW/D mice inoculated at birth with a neurovirulent mutant (ts1) of Moloney murine leukemia virus (MoMuLV), nonneurovirulent wild type (wt) MoMuLV, and conditioned virus-free medium were studied comparatively by immunohistochemistry, lectin histochemistry and light microscopy. Cellular targets for viral antigen expression in the eye were identical in both ts1 and wt MoMuLV-infected mice. Viral antigen first was observed in endothelial cells of the retina and subsequently spread in a spatial and temporal pattern consistent with normal vascularization of the developing retina. The virus also was observed in (1) epithelial cells of the bulbar and palpebral conjunctiva, ora ciliaris retinae, and lacrimal gland; (2) endothelial cells of the ciliary body, iris, choroid, and sclera; (3) amacrine cells of the retina; and (4) smooth muscle cells and endothelia of the periocular muscle. Although ts1 MoMuLV induced a spongiform encephalopathy in the brain and spinal cord, structural lesions were not observed in the retina or other ts1 MoMuLV-infected ocular structures; differentiation of the retina was normal. The lectin Ricinus communis agglutinin I (RCA-I) labeled (1) endothelial cells of the hyaloid vessels, tunica vasculosa lentis, retina, ciliary body, iris, choroid, and sclera; (2) epithelial cells of the cornea, bulbar and palpebral conjunctiva, ora ciliaris retinae, and lacrimal gland; (3) smooth muscle cells and endothelia of the periocular muscle; (4) inner segments of the photoreceptor layer; and (5) amacrine cells of the retina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740370 TI - Electrode comparison in pattern electroretinography. AB - In recent years, there has been great interest in recording the pattern electroretinogram (PERG) in glaucomatous and diabetic populations. The Dawson, Trick, and Litzkow thread electrode (DTLTE) and the gold foil electrode (GFE), commonly used for recording PERGs, were compared for variations in amplitude of response, test-retest variability, and patient comfort. Two study centers collected data on a total of 32 normal subjects. The subjects from the London center showed a slight (but not significant) preference for the DTLTE, and the Houston subjects also found the DTLTE to be significantly more comfortable (chi square = 39, P less than 0.001). In both study groups, the GFE was found to produce a statistically larger amplitude of response than that obtained with the DTLTE. Significant differences were found regardless of the slow (transient, 3.1 Hz; F = 6.24; P = 0.0192) or fast (steady state, 8.3 Hz; F = 18.38; P = 0.0001) stimulus-presentation rate. Larger differences between the two electrodes occurred under steady-state conditions. Although there is no consensus as to the optimum recording conditions to obtain the subtle PERG, it appears the the GFE records larger responses than the DTLTE. However, test-retest data confirmed that the GFE records twice the amplitude of the DTLTE, and it also produced twice the variability (average percent difference over time for GFE, 15%; for DTLTE, 8%). PMID- 1740371 TI - Boron neutron capture therapy of anterior chamber melanoma with p boronophenylalanine. AB - Boron neutron capture therapy (BNCT) is a form of radiation therapy that requires selective uptake of boron by the tumor and irradiation with thermal neutrons. Phenylalanine is an amino acid precursor of melanin and when boronated (p boronophenylalanine [BPA]) was found to be selectively taken up by Greene melanoma cells in the anterior chamber of rabbits. This tumor model was irradiated 24 hr after oral administration of BPA and was used for biodistribution studies that compared BPA and sodium pentaborate. Three groups were irradiated: group 1 (11 rabbits) received BPA followed by thermal neutron irradiation, group 2 (9 rabbits) received thermal neutron irradiation only, and group 3 (9 rabbits) served as unirradiated, undrugged control animals. Eight of the 11 tumors in group 1 were treated successfully; all tumors in groups 2 and 3 grew. Histopathologic examination did not reveal vascular or retina damage in group 1. These preliminary experiments confirm that newer boronated compounds, such as BPA, used in BNCT and improved neutron beams can provide selective irradiation of ocular melanomas. PMID- 1740372 TI - Hyperthermia reduces the occurrence of proliferative vitreoretinopathy in a rabbit model. AB - The effects of hyperthermia on experimental proliferative vitreoretinopathy (PVR) in rabbits were studied. Heat treatment (42.4 degrees C for 30 min) of the retinal surface (as estimated from temperature measurement of the retrobulbar space) 2 to 3 hr after fibroblast injection reduced the occurrence of traction retinal detachment compared with control rabbits (P less than 0.02), but the incidence of pucker formation plus traction detachment was not significantly different between the two groups. In a separate experiment, heat treatment applied to normal rabbit eyes showed only reversible elongation in the latency of the electroretinographic b-wave without affecting the amplitude. Histologic examination revealed no significant changes in the heat-treated normal rabbit retina. Hyperthermia may be used as a new therapeutic tool for PVR. PMID- 1740373 TI - In situ measurements of lens fluorescence and its interference with visual function. AB - Irradiation of the primate lens by near-ultraviolet wavelengths results in a blue fluorescence, which can be an intraocular source of veiling glare. This study quantitated the fluorescence intensity as a function of exciting intensity and wavelength. As the exciting wavelength was increased from 360 to 430 nm, the decreasing fluorescence intensity (for equal radiant exposures) was partially offset by a shift in the fluorescence spectrum to wavelengths of greater luminous efficiency so the luminance of the lens fluorescence remained approximately constant. The measured luminance of the lens fluorescence was high enough to imply degradation of visual function as a result of reduced contrast of the retinal image. To obtain an objective measure of visual deficit associated with the fluorescent glare, the visual evoked potential (VEP) elicited by counterphased sine-wave gratings was recorded while the subject eye was continuously exposed to the 413 nm emission from a krypton laser. The VEP amplitude was reduced in the presence of the exciting laser even at levels defined as "safe" (ie, where exposure levels are insufficient to induce an acute ocular lesion). Because the direct glare effect of the exciting radiation was negligible in this experiment, the VEP response loss is attributed to the effect of the lens fluorescent glare. PMID- 1740374 TI - Effects of pilocarpine and tropicamide on blood-aqueous barrier permeability in man. AB - The time courses of changes in the effects of topical pilocarpine and tropicamide on the index of the blood-aqueous barrier permeability to plasma protein (Pin) were determined in normal volunteers. Before and after drug instillation in one eye, protein concentration in the anterior chamber (Ca) was determined from aqueous flare intensity with a laser flare-cell meter and from aqueous flow by fluorophotometry. The Pin was calculated from the Ca, plasma protein concentration, and aqueous flow. One percent pilocarpine produced a maximum increase of 21 +/- 10% in the Ca (mean +/- SEM, n = 10), no significant change in the aqueous flow (n = 5), and a maximum increase of 29 +/- 10% in the Pin (n = 10). Three percent pilocarpine produced a maximum increase of 55 +/- 11% in the Ca (n = 8), a maximum increase of 34 +/- 13% in the aqueous flow (n = 5), and a maximum increase of 74 +/- 18% in the Pin (n = 8). Tropicamide (0.4%) produced a maximum decrease of 17 +/- 7% in the Ca (n = 8), a maximum decrease of 15 +/- 11% in the aqueous flow (n = 8), and a maximum decrease of 24 +/- 13% in the Pin (n = 8). The results indicated that pilocarpine increased the blood-aqueous barrier permeability to plasma protein in a dose-dependent manner and that tropicamide reduced it. PMID- 1740375 TI - Localization of smooth muscle and nonmuscle actin isoforms in the human aqueous outflow pathway. AB - alpha-Smooth muscle actin is the isoform of actin restricted to vascular smooth muscle, pericytes, myofibroblasts and, certain other cells that are of myoid origin. We investigated the distribution of alpha-smooth muscle actin and nonmuscle specific filamentous actin in the human aqueous outflow system by immunohistochemical methods. Filamentous actin was observed in all cellular constituents of the outflow pathway, while distribution of alpha-smooth muscle actin was restricted to the ciliary muscle, to specific cells throughout the trabecular meshwork, and to cells adjacent to the outer wall and the collector channels. The ciliary muscle extended deep into the corneoscleral meshwork, far anterior to the scleral spur. These findings agree with our previous study localizing the distribution of smooth muscle myosin in the human aqueous outflow pathway. Although functionality of the immunoreactive cells needs to be demonstrated, our data show that a potentially contractile apparatus exists in a subpopulation of trabecular meshwork cells and in certain cells of the more distal components of the outflow system. PMID- 1740376 TI - Visual evoked potentials after photostress in patients with primary open-angle glaucoma and ocular hypertension. AB - Visual evoked potentials (VEPs) were assessed in basal condition and after photostress in normal subjects, in subjects with ocular hypertension (OHT), and in subjects with primary open-angle glaucoma (POAG). The VEPs recorded in basal condition showed that in patients with OHT and POAG a latency of the P100 peak was higher than in controls. The amplitudes were reduced in POAG patients but not in OHT patients. In all eyes, the VEPs recorded 20 s after photostress showed an increase in latency and a decrease in amplitude. In the control eyes, the functional recovery was complete after 80 s. In the eyes with OHP and in the eyes with POAG, the parameters of VEP after photostress underwent greater changes than in the control eyes. VEPs were superimposable on the basal condition (recovery time) at 73.2 s in OHT patients and at 113.2 s in POAG patients. The longer VEP recovery time after photostress observed in OHT and POAG patients could be attributed to the reduced functionality of the outer layers or the inner retinal layers of the central retina, or both. This test may be useful in the clinical evaluation for early diagnosis of glaucoma. PMID- 1740377 TI - Apparent accommodation in pseudophakic eyes as measured with visually evoked potentials. AB - We measured apparent accommodation with pattern reversal visually evoked cortical potentials in 27 pseudophakic eyes after the implantation of posterior chamber intraocular lenses. The patients ranged in age from 47-83 years. The amplitude of accommodation was not significantly different between pseudophakic eyes and normal phakic eyes. Apparent accommodation was inversely proportional to the pupillary diameter and was significantly correlated with corneal astigmatism. No significant relationship was noted between apparent accommodation and age of patients, corrected visual acuity, or refractive error. PMID- 1740378 TI - Partially deficient glutamate dehydrogenase activity and attenuated oscillatory potentials in patients with spinocerebellar degeneration. AB - Glutamate dehydrogenase (GDH, EC 1.4.1.2) catalyzes the synthesis and degradation of glutamate, an excitatory neurotransmitter in the retina. Recently, two forms of GDH, a soluble heat-stable form and a particulate heat-labile form, have been demonstrated to be deficient in some types of spinocerebellar degeneration (SCD). We measured these forms of GDH activity in leukocyte homogenate from patients with SCD (n = 22) and normal subjects (n = 20) who were examined ophthalmoscopically and electrophysiologically. Seven patients with SCD showed attenuated oscillatory potentials (OPs) on electroretinography. The heat-labile GDH activity in these seven patients (78 +/- 51 nmol/mg protein/h) was significantly lower than that of 15 patients with normal OPs (367 +/- 189) and the normal subjects (397 +/- 1720 (P less than 0.001). Our results indicated that patients with SCD could be separated into two groups electrophysiologically, one with normal OPs and one with attenuated OPs. Also indicated was that a deficiency of heat-labile GDH might affect some functions of neural elements in the retina that are responsible for the generation of OPs. PMID- 1740379 TI - Comparison of prednisolone and RMI-1068 in the ocular irritative response in dogs. AB - Ocular inflammation was induced in 36 dogs by performing an anterior capsulotomy with a Nd:YAG laser. All dogs were pretreated with topical atropine. Dogs were then divided into three groups: (1) control, with no other pretreatment; (2) pretreatment with the topical dual cyclooxygenase/lipoxygenase inhibitor RMI 1068; and (3) pretreatment with topical prednisolone acetate. Dogs were studied 1 3 hours after lasering. RMI-1068 maintained mydriasis and raised intraocular pressure compared to the control and prednisolone groups. An ocular fluorophotometer used to measure anterior chamber fluorescence after IV injection of sodium fluorescein showed that RMI-1068 decreased anterior chamber fluorescein concentration compared to the control and prednisolone groups. RMI-1068 decreased PGF2 alpha concentrations in the aqueous at 1 and 3 hours compared to the control and prednisolone groups. Prednisolone decreased PGF2 alpha concentrations compared to the control group at 1 h. Concentrations of LTB4 in the aqueous at 1 hour were lower in the RMI-1068 group than in the control and prednisolone groups. PMID- 1740380 TI - Enhanced induction of a 72 kDa heat shock protein in cultured retroocular fibroblasts. AB - Fibroblasts in the retroocular connective tissue appear to play a central role in the pathogenesis of Graves' ophthalmopathy (GO). We hypothesize that specific attributes, differentiating normal from GO retroocular fibroblasts, may render the latter more vulnerable to the ongoing immunopathological process in GO. We investigated whether GO fibroblasts differ from normal fibroblasts with respect to their sensitivity and capacity to express the inducible 72 kDa heat shock protein (HSP) in response to stressful environmental stimuli. Cultured retroocular fibroblasts derived from patients with GO and normal individuals were exposed to various changes in the culture medium that may simulate conditions in the affected retroocular space in vivo. HSP 72 reactivity was determined using sodium dodecyl sulfate polyacrylamide-gel electrophoresis of cellular extracts, followed by immunoblotting with a mouse monoclonal anti-HSP 72 antibody and quantitative scanning densitometry. In addition, indirect immunofluorescence was performed on parallel fibroblast monolayers. Following exposure to heat and acidic pH, deprivation from nutrients, and high monolayer density, GO fibroblasts expressed HSP 72 with significantly greater sensitivity and in significantly higher abundance than did normal fibroblasts. These results demonstrate that changes in the physiological environment induce HSP 72 expression in cultured fibroblasts. The enhanced sensitivity and capacity of GO retroocular fibroblasts to express the inducible HSP 72 in response to stressful stimuli may play a role in the autoimmune process affecting the retroocular space in GO. PMID- 1740381 TI - Monoclonal antibody specific for the cellular receptor of echoviruses. AB - Cell lines of primate origin carry membrane receptors which are specific for echoviruses (EV). The present report describes isolation and characterization of a monoclonal antibody (Mab 143) reacting with the membrane of KB cells. The Mab was selected for its protection of different cell lines from primate origin against the CPE of EV-11. This protection was found to extend to most EV serotypes and to coxsackievirus A9, while the replication of several other picornaviruses was not affected. The fluorecein isothiocyanate labelled Mab did not react with cell lines from bovine, canine, or rabbit origin, but bound specifically to the cell lines from human or simian origin. These results suggest that a unique receptor site is used by most EV serotypes for binding onto and penetration into susceptible cells. PMID- 1740382 TI - Properties of the Mentha strain of lychnis ringspot virus. AB - A hordeivirus isolated from horsemint (Mentha longifolia Huds.) was designated as the mentha strain of lychnis ringspot virus (LRSV-M) on the basis of serological relationship with the type strain (LRSV-T) and similarities in nucleotide sequence and properties of genomic and replicative RNAs of the two strains. Four ssRNAs in addition to the three genomic RNAs were encapsidated by LRSV-M coat protein. No genomic sequence similarity was detected between LRSV-M and either barley stripe mosaic or poa semilatent viruses under high stringency conditions, confirming that the hordeiviruses are a group of morphologically similar, but genomically distinct viruses. PMID- 1740383 TI - Isolation and characterization of the measles virus strains with low hemagglutination activity. AB - Six measles virus strains were isolated from clinical specimens. They differed from a prototype strain in being incapable to grow in cell lines derived from monkey kidney and having a slower electrophoretic mobility of the hemagglutinin protein and a very low hemagglutination activity. PMID- 1740384 TI - Isolation and characterization of a portal protein-DNA complex from dsDNA bacteriophage. AB - A portal protein-DNA complex was isolated from bacteriophage disrupted in 70% acetic acid. This treatment dissociated most of the phage structural proteins, while the portal protein ring remained attached to the highly condensed naked DNA. In the absence of a headful of DNA, the portal ring was not protected. Purification of the portal ring-DNA complex by density gradient centrifugation showed that a dsDNA fragment of about 40 bp was protected from DNase digestion by this association, suggesting it was internalized within the 140 A long, 20-40 A in diameter T4 apical channel of the ring dodecamer. A portal ring-DNA complex could be isolated from a number of phages (T4, T7, Phi29), and the end(s) of phage T7 DNA was (were) found to be preferentially associated with the ring complex. PMID- 1740385 TI - Absence of a gene dosage effect during bacteriophage T3- and T7-coded RNA polymerase synthesis. AB - The rates of synthesis of phage-coded RNA polymerase upon infection of Escherichia coli by bacteriophages T3 or T7 were measured at different MOIs under permissive and non-permissive conditions. At MOIs from 1 to 15, these rates did not vary appreciably, at MOIs of about 20 there was a slight depression in the synthesis rate. The reason for this absence of a positive gene dosage effect is unknown. PMID- 1740386 TI - Comparison of health expenditures in U.S. and Hawaii economies. PMID- 1740387 TI - America's pharmaceutical research companies: keeping the cost of health care down. Pharmaceutical Manufacturers Association. PMID- 1740388 TI - Hereditary anemias in Hawaii: an update. PMID- 1740389 TI - Maintaining the supply and monitoring the quality of the blood bank. PMID- 1740390 TI - Does improved depth dose characteristics and treatment planning correlate with a gain in therapeutic results? Evidence from past clinical experience using conventional radiation sources. AB - Experience with the use of external beam conventional radiation over a period of several decades has shown that in every instance where there has been a major advance in the physical delivery of radiation to the tumor (beam energy and characteristics and precise tumor dose delivery) there has been a corresponding major improvement in the treatment results. The advent of megavoltage sources following the invention and use of Cobalt 60 and medical linear accelerator units during the late 1940's and early 1950's and their major impact on tumor control and patient survival in solid tumors such as carcinoma of the prostate, Hodgkin's Disease, head and neck tumors and cancer of the cervix are being discussed. Most recently, the use of computerized tomography and computer systems for treatment planning is likely to show a further improvement in the therapeutic results. PMID- 1740391 TI - Normal tissue complication probabilities: variable dose per fraction. AB - Because of the large amount of data generated by 3D treatment planning, new tools are being developed for the evaluation and optimization of the plans. Estimates of the probability of local control of the tumor and for the probability of specific normal tissue complications are among the new tools. The normal tissue complication probability (NTCP) is based on clinical estimates of the tolerance doses for specific tissues/organs. These tolerance doses are assumed to apply for uniform partial and full volume irradiations delivered at 2 Gy per fraction and 5 fractions per week. A different tolerance dose may apply when the dose is delivered at a different dose per fraction and over a different period of time. This study evaluates the maximum change expected in the NTCP when the normal structure receives the dose at a different dose per fraction than the target volume due to different choices in the delivery of the daily fraction. PMID- 1740392 TI - New imaging technologies: prospects for target definition. AB - Developments in medical imaging over the past 2 decades are providing significant improvement in tumor definition. Improvements in soft tissue visualization with tumor specific contrast combined with direct 3D data acquisition and millimetre spatial resolution set new standards in tumor definition. Such precision in tumor imaging provides a new level of challenge for precision radiation treatment. Significant further improvement over the next decade in geographic definition is unlikely. The challenge for imaging research is that of extracting tissue specific information about tumors such as perfusion and response to therapy rather than simply anatomical clarity. PMID- 1740393 TI - Charged particle radiotherapy of paraspinal tumors. AB - Between 1976 and 1987, 52 patients with tumors adjacent to and/or involving the cervical, thoracic, or lumbar spinal cord were treated with charged particles at the University of California Lawrence Berkeley Laboratory. The histologies included chordoma and chondrosarcoma (24 pts), other bone and soft tissue sarcoma (14 pts), and metastatic or unusual histology tumors (14 pts). Radiation doses ranged from 29 to 80 Gray-equivalent (GyE), with a median dose of 70 GyE. Twenty one patients received a portion of their treatment with photons. Median followup was 28 months. For 36 previously untreated patients, local control was achieved in 21/36 patients and the 3-year actuarial survival was 61%. Of 16 patients treated for recurrent disease, 7/16 were locally controlled and the 3-year actuarial survival was 51%. For patients treated for chordoma and chondrosarcoma, probability of local control was influenced by tumor volume (less than 100 cc or greater than 150 cc) and whether disease was recurrent or previously untreated. Complications occurred in 6/52 patients, including one spinal cord injury, one cauda equina and one brachial plexus injury, and three instances of skin or subcutaneous fibrosis. Charged particle radiotherapy can safely deliver high tumor doses to paraspinal tumors with good local control. PMID- 1740394 TI - Conformal radiotherapy for unresectable retroperitoneal soft tissue sarcoma. AB - Local tumor control remains a continuing challenge in the treatment of retroperitoneal soft tissue sarcoma. Though complete resection by means of wide excision or excisional biopsy can be performed in a minority of patients only, aggressive surgical approach remains the treatment of choice. Unresectable sarcoma can rarely be controlled by conventionally applied radiotherapy--only a few percent of patients survive. A superior dose distribution of external radiation is demanded in order to spare healthy tissue. The presumably greatest advantage will occur when radiotherapy is used preoperatively. The possible clinical gain of superior dose distribution is demonstrated by results of the dynamic, 3-D conformal pion radiotherapy at PSI. Between April 1983 and June 1988 a total of 21 patients were treated with high doses (greater than or equal to 30 Gy) for unresectable retroperitoneal soft tissue sarcoma. The follow-up time is 13-74 months, median 24. Fifteen patients were treated with 20 fx, and 19 patients were treated with fraction sizes of 150 or 165 cGy. Except for one patient with thrombocytopenia after chemotherapy, no treatment interruption was necessary. Five patients developed late reactions, caused also by surgery and chemotherapy: two intestinal obstructions, one liver abscess, one leg edema, and one superficial skin necrosis. Nine patients had laparotomy after pion irradiation, five for resection of the previous unresectable tumor; 3/5 sarcoma were completely resected. Morbidity rate after post-pion laparotomy did not increase. Three patients had local tumor progression, 1/3 inside the treatment volume. The actuarial five-year local tumor control rate of these unresectable retroperitoneal sarcoma is 60%, the actuarial five-year survival rate is 33%. Out of the 21 patients, 15 are alive, two have died from local progression, one from peritoneal progression, and three from metastases. PMID- 1740395 TI - Potential improvement in the results of irradiation for prostate carcinoma using improved dose distribution. AB - Results for radiation treatment of prostate carcinoma indicate that nearly one third of Stage C patients fail locally. This number will likely increase as occult failures are discovered by monitoring serum prostate specific antigen levels. Thus, there is need for techniques that would increase the local control of prostatic carcinoma. Using cross-sectional imaging and 3-dimensional treatment planning, dose distributions for photon irradiation can be created that conform more closely to the shape of the prostate and seminal vesicles, sparing additional dose to portions of bladder and rectum. A dose escalation trial is underway to investigate whether these techniques will lead to increased local control without unacceptable increases in bladder and rectal complications. While zero local failures is probably an unattainable goal, reduction in local failure in prostate cancer would likely increase the overall cure rate in this disease. PMID- 1740396 TI - The proton treatment center at Loma Linda University Medical Center: rationale for and description of its development. AB - Proton radiation, a continuation of radiation oncology's historic search for an optimum dose distribution, offers superior characteristics for clinical radiation therapy. A complete facility for clinical proton radiation therapy has been designed for and constructed at Loma Linda University Medical Center. To bring about this achievement, a consortium of engineers, physicists, and physicians interested in the clinical applications of protons was necessary. The accelerator, the beam transport and delivery systems, the building, and the personnel who operate the system were all brought together to fully exploit the properties of protons for patient treatments, which are now underway. PMID- 1740397 TI - Three dimensional vector analysis of the spatial components and voltage magnitudes of the P300 response during different attentional states and stimulus modalities. AB - The spatial orientation and vector magnitude of the P300 event related potential (ERP) were investigated under both passive and active attentional states using stimuli presented to two sensory modalities. Three orthogonal electrode pairs were used to establish a tri-axial reference frame. By combining the separate single channel data recordings into a Cartisian coordinate system, both the spatial orientation and the vector magnitude of the P300 response could be derived and described as a hypothetical dipole. Results suggested that changes in amplitudes, recorded with individual electrode pairs, can be attributed largely to changes in the spatial orientation of a rotating P300 response dipole, and not simply to the altered magnitude of the response. The combined-axes P300 response occurs in two separate spatial domains, depending on stimulus modality and attentional state. PMID- 1740398 TI - The influence of monocular viewing on heart period variability. AB - Monocular viewing seems to differentially activate the cerebral hemispheres. Viewing with only one eye is accompanied by a relatively greater activation of the contralateral hemisphere. In this study heart periods were measured during binocular, left and right monocular viewing in 29 right-handed males. Power spectral analysis of heart period variability showed that the amount of heart rate fluctuations in the 0.07-0.13 Hz frequency range (the mid-frequency peak of the spectrum) depends on the viewing eye. Only viewing with the left eye produced a significant increase of the mid-frequency peak. It is known that sympathetic activity contributes strongly to the mid-frequency component of the heart rate. Therefore, it is concluded that the effects of left monocular viewing result in an increased sympathetic influence on the sinoatrial node. PMID- 1740399 TI - Psychophysiological indices of cerebral maturation. AB - Maturation (1-21 yr) trajectories for quantitative electroencephalographic (QEEG) frequency spectra are presented for four regions of the human brain. The results show that all four regions exhibited discontinuous maturation rates: five stages were identified. The stages were synchronous across regions during the first 10 1/2 years of life. Thereafter, the four maturation trajectories became independent of one another. Interestingly, a major maturational advance was recorded from the frontal regions, during late adolescence. The relationships between these findings to maturation rates in skull volume, cortical thickness, cortical volume and nerve cell density measurements was discussed. These converging results indicate that the observed QEEG stages can reliably be interpreted as landmarks in cerebral maturation. PMID- 1740400 TI - Thinking with images or thinking with language: a pilot EEG probability mapping study. AB - This pilot EEG mapping study was designed to explore thinking processes using complex mental imagery and thought processes. EEG was recorded with 19 electrodes (10/20 system against averaged ear lobe signals) while volunteers (n = 42) performed two separate tasks: visualization of an abstract concept and interpretation of a painting. Average spectral parameters such as amplitude, local and interhemispheric coherences were computed for five frequency bands (theta, alpha, beta 1, 2 and 3). Results indicate that the frontal regions are strongly involved during these tasks as evidenced by coherence changes. Changes are also present in temporal, parietal and occipital regions and are discussed in relation to information processing with the frontal regions considering the different cognitive functions required by the tasks. PMID- 1740401 TI - Stimulus rise time, intensity and the elicitation of unconditioned cardiac and electrodermal responses. AB - In recent discussions on the differentiation of orienting, startle and defense responses, the importance of stimulus rise time for the elicitation of different cardiac response patterns was re-emphasized. Especially, it has been claimed that phasic accelerative heart rate (HR) responses-interpreted as indicators of startle-might not only be evoked by auditory stimuli with instantaneous rise times and high intensities, but also by low to moderate stimulus intensities with sudden onsets. The present study examined this question by manipulating rise time (instantaneous vs. 50 ms) and intensity (60 vs. 95 dB). Subjects (N = 120) were randomly assigned to one of the four independent groups. They performed a habituation experiment in which 12 tones of 1000 Hz with a constant interstimulus interval of 90 s were presented. On trial 13, a change in rise time was introduced by reversing the rise time condition in each group (i.e., from instantaneous to 50 ms and vice versa). Examination of HR changes across 4 poststimulus seconds, of maximal HR deceleration and acceleration, as well as examination of magnitude of skin conductance responses (SCRs) indicated clear intensity effects. Rise time, on the other hand, had no effects on HR and SC that could be interpreted as indicative of startle. Thus, it could neither be observed that instantaneous rise time led to stronger accelerative HR responses nor that the combination of instantaneous rise time and high intensity elicited anything but a dominant accelerative response pattern. These findings were also obtained when the first four trials were analyzed separately. As a consequence of stimulus change, larger SCRs as well as larger decelerative HR responses were observed without, however, being affected by the direction of the change in rise time. In sum, the present study suggests that the role attributed to rise time with respect to eliciting qualitatively different cardiac response patterns has been exaggerated. The consequences for the differentiation of different unconditioned responses are briefly addressed. PMID- 1740402 TI - The law of initial values: a four factor theory. AB - The effects of four factors, measurement error, skewness, floor/ceiling effects, and reactivity, on the correlation between change and initial level were studied using computer simulations. A total of 24 conditions were simulated: the four factors being examined together with variations in the direction of change, level of measurement error and/or strength of effect. In each condition ten random samples of 50 cases were generated by SPSSX, and compute functions were used to model the effects of interest. Three factors were capable of producing a negative correlation (the Law of Initial Values, LIV): measurement error, skewness, and floor/ceiling effects. Two factors yielded a positive correlation (anti-LIV effect): reactivity and skewness. The issue of how to determine which factor is operating in a given situation is discussed. PMID- 1740403 TI - Identification and standardization of bilateral electrodermal parameters of learning abilities and disabilities. AB - Data are presented for identified and standardized bilateral electrodermal parameters of normal subjects with learning abilities and those with learning disabilities during cognitive workload in three different sessions. The electrodermal parameters are presented in terms of specific mumhos and represent the first identification and standardization of human abilities and disabilities. It was found that normal subjects had an electrodermal activity level which ranged between 6.5-8.5 mumhos bilaterally. Furthermore, 15 sub-groups of subjects with learning disabilities were identified based on their Left and Right electrodermal activity levels. They could be grouped under three main categories: (1) those subjects with lower than 5.01 mumhos Left and/or Right electrodermal activity level; (2) those with higher than 10.1 mumhos Left and/or Right activity level; and (3) those with mixed electrodermal activity having lower than 5.01 mumhos Left and/or Right activity in one session and higher than 10.1 mumhos activity in another session. These identified and standardized parameters have clinical implications and applications for the electrophysiological evaluation and psychophysiological treatment of learning disabilities. PMID- 1740404 TI - Responsiveness patterns and handedness differences in bilateral electrodermal asymmetry. AB - The aim of the present study was to examine the relationship between subjects' handedness and electrodermal asymmetry when subjects were divided according to their electrodermal Responsiveness Patterns, obtained during a stimulus-free period. Skin conductance was bilaterally recorded in a sample of 48 subjects (24 dextrals and 24 sinistrals) during the performance of two tasks (watching a film and listening to neutral tones). Subjects were divided into four groups of 12 subjects each (dextral right-hand responders, dextral left-hand responders, sinistral right-hand responders and sinistral left-hand responders). No differences were found between dextral and sinistral subjects. Orientation of electrodermal asymmetry in each Responsiveness Patterns remained constant throughout the two conditions: right-hand responders showed higher electrodermal activity on their right hand, while left-hand responders showed higher electrodermal activity on their left hand. In addition, left-hand responders showed a slower habituation rate on their left hand than on their right hand, whereas right-hand responders showed no significant differences between hands. PMID- 1740405 TI - The effects of stress-anxiety and coping styles on heart rate variability. AB - This study explored the effects of a naturally occurring stressor on the amplitudes of the respiratory sinus arrhythmia and Traube-Hering-Mayer bands of the power spectra of cardiac interbeat intervals of 15 Highly Anxious, 15 Truly Low Anxious and 15 Repressor women. Interbeat interval samples were obtained from 4.5 min tachygraph records while the subjects sat quietly 2 weeks before (2W), the day before (DB) and 1 week following (WA) their oral comprehensive examinations. Subjects also reported their state anxiety on each occasion. Repeated measures ANOVA indicated that subjects' state anxiety was greater on the DB than on the other two occasions. Heart rates were faster for the DB than for the 2W and WA occasions. Truly Low Anxious women had slower heart rates, across all occasions, than did Repressors or Highly Anxious women. Although respiratory sinus arrhythmia amplitudes did not differ across occasions, RSA amplitudes were smaller for individuals with high trait anxiety (Repressors and Highly Anxious) than for subjects with low trait anxiety (Truly Low Anxious). Traube-Hering-Mayer amplitudes were smaller on the DB than the 2W or WA occasions for all subjects and were smaller for Repressors or Highly Anxious women than for Truly Low Anxious women across occasions. PMID- 1740406 TI - Cardiovascular reactivity assessment: effects of choice of difficulty on laboratory task responses. AB - This laboratory study of cardiovascular reactivity was designed to examine how a choice of difficulty element in a mental arithmetic task would affect cardiovascular responses. 20 healthy male subjects were tested on a computer controlled mental arithmetic task, designed to standardize performance across subjects by keeping constant the proportion of correct responses. This was achieved by automatic adjustment of problem difficulty according to ongoing performance. Subjects were led to believe that they could take either a 'difficult' or an 'easy' version of the mental arithmetic task and were asked to make a choice; in fact, all subjects were given the same task. Subjects who chose the 'difficult' mental arithmetic task (N = 10) showed significantly greater increases in myocardial contractility, cardiac output and systolic blood pressure during task performance than those who chose 'easy' (N = 10). However, subjects who chose 'difficult' were presented with more difficult problems presumably due to their exerting greater levels of effort during the task. The differences in cardiovascular responses associated with choice of difficulty were absent during testing on four subsequent tasks which did not incorporate any choice options (reaction-time, speech, mirror trace, cold pressor). These findings are interpreted as being provocative, rather than in any way conclusive. Nevertheless, they are suggestive of the possibility that choice of difficulty in laboratory tasks may be one strategy for improving the ecological validity of laboratory reactivity assessment procedures. PMID- 1740407 TI - Protein disulfide isomerase. A multifunctional protein resident in the lumen of the endoplasmic reticulum. PMID- 1740408 TI - Cloning and functional expression of a mammalian Na+/nucleoside cotransporter. A member of the SGLT family. AB - Complementary DNAs encoding seven different proteins related to the rabbit intestinal Na+/glucose cotransporter, SGLT1, were isolated from a rabbit renal cDNA library at relatively high stringency. The messages for RK-B to RK-F were single mRNA species at 2.3 kilobases (kb) in heart and kidney. The message for RK A was 4 kb and was found in brain, lung, intestine, liver, and kidney. RK-I mRNA was approximately 3 kb and was found in all tissues tested. The most abundant clone, RK-C, constituted nucleotides 66-2150 of the sodium-nucleoside cotransporter, SNST1. The 672-amino acid protein encoded by SNST1 is 61% identical and 80% similar in sequence to SGLT1. Expression of SNST1c in Xenopus oocytes resulted in nucleoside-stimulated 22Na uptake and sodium-dependent [3H]uridine uptake. The uptake of [3H]uridine was inhibited by a range of nucleosides, including the anti-human immunodeficiency virus drug, dideoxycytidine. The results of this study show that there is a family of SGLT1 related proteins found in a wide variety of tissues and that one of these is a Na+/nucleoside cotransporter. PMID- 1740409 TI - The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C dependent mechanism. AB - Tissue factor (TF) is an integral membrane glycoprotein that serves as a cellular receptor and cofactor for the activation of the plasma protease factor VII. TF activity in both monocytes and endothelial cells is regulated by various cytokines and mitogens, including the protein kinase C (PKC) activator phorbol 12 myristate 13-acetate (PMA). Three TF constructs (full-length human, a cytoplasmic domain deletion mutant, and a human-rat TF chimera), expressed in a human kidney cell line, were used to examine the in vivo phosphorylation state of TF after PMA treatment. The cytoplasmic domains of both rat and human TF were rapidly phosphorylated after cells were treated with 10-100 nM PMA. This response was completely abolished by preincubating cells with staurosporine, the potent PKC inhibitor, prior to PMA treatment. Localization of the phosphorylation site(s) to the cytoplasmic domain was demonstrated using a deletion mutant of TF and by CNBr digestion at the single methionine residue (Met-210) in the TF sequence. The rat TF cytoplasmic domain was phosphorylated to a higher specific activity than the human TF cytoplasmic domain. Phosphoamino acid analysis of the chimeric TF revealed both phosphothreonine and phosphoserine, whereas human TF contained only phosphoserine. Thus both potential phosphoacceptor sites are phosphorylated in the rat TF cytoplasmic domain. Alignment of TF cDNA sequences of mouse, rat, rabbit, and man revealed that the phosphoacceptor site (X-S*/T*-P-X, where asterisk indicates the phosphorylated residue) in the cytoplasmic domain has been conserved through evolution. PMID- 1740410 TI - Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers. AB - Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand. PMID- 1740411 TI - Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture. AB - Elevated fibronectin (Fn) and Fn fragment concentrations are found in the synovial fluid of osteoarthritic and rheumatoid arthritic patients. Fn has been shown to affect expression of chondrocytic matrix proteins, and Fn fragments have been shown to elevate gene expression of neutral proteinases in synoviocytes. For these reasons, we tested the effects of Fn fragments on protease release and resultant proteoglycan release from cartilage in serum-free bovine articular cartilage explant cultures. We have found that 1 microM amino-terminal 29- and 50 kDa gelatin-binding Fn fragments caused over a 50-fold enhancement of gelatinolytic and collagenolytic proteinase release with a 23-fold enhancement of proteoglycan (PG) release. Release was significant at fragment concentrations as low as 20 nM. An integrin-binding 140-kDa fragment mixture was the least active fragment, whereas native Fn had little activity. The relative activities of the fragments correlated with their relative abilities to bind to cartilage. The RGDS integrin-recognition peptide also caused release, although sequence mutants did not. PG release was blocked by actinomycin D, cycloheximide, and deoxyglucose. Fn fragment-mediated PG release was decreased in 10% serum by over 10-fold but was still 2-fold greater than in controls. In the presence of insulin-like growth factor-1, PG release was as great as without serum. We suggest that Fn fragments, as found in diseased synovial fluid, may contribute to protease-mediated damage to cartilage. PMID- 1740412 TI - Activation of protein kinase C by oleic acid. Determination and analysis of inhibition by detergent micelles and physiologic membranes: requirement for free oleate. AB - Sodium oleate is able to activate soluble protein kinase C (Murakami, K., Chan, S. Y., and Routtenberg, A. (1986) J. Biol. Chem. 261, 15424-15429) but is unable to activate membrane-bound enzyme (El Touny, S., Khan, W., and Hannun, Y. (1990) J. Biol. Chem. 265, 16437-16443). Because physiologic interactions of fatty acids with protein kinase C occur in the presence of membranes, the following studies were conducted to evaluate the effects of surfaces (detergent micelles or platelet membranes) on the activation of protein kinase C by oleate. At concentrations at or above the critical micellar concentration (CMC) of Triton X 100, oleate was present primarily in Triton X-100/oleate-mixed micelles, as determined by gel permeation chromatography and equilibrium dialysis binding studies. At concentrations slightly below the CMC for Triton X-100, the presence of oleate caused the formation of a limited number of mixed micelles. Studies of the dose-dependent activation of purified platelet protein kinase C by sodium oleate in the presence of different concentrations of Triton X-100 indicated that only unbound oleate was able to activate protein kinase C. Platelet protein kinase C was resolved into two major isoenzymes (types II (beta) and III (alpha)) which displayed nearly identical interaction with oleate. Activation of protein kinase C by oleate in a physiologic setting employing platelet substrates and endogenous platelet protein kinase C was investigated. Oleate potently activated protein kinase C in the cytosolic compartment. In platelet homogenates as well as in a reconstituted platelet cytosol and membrane system, the dose dependence of protein kinase C on oleate showed a significant shift to the right. Approximately 30% of oleate was associated with platelet cytosol and 70% was associated with platelet membranes. Partitioning of oleate into the two platelet compartments showed little change with pH, temperature, or duration of incubation. When corrected for free oleate concentration, activation of protein kinase C by oleate showed identical dose dependence in cytosol and homogenate. Arachidonate, a potential physiologic activator of protein kinase C, showed similar behavior as oleate although only 30% of arachidonate partitioned into platelet membranes with the majority of arachidonate (70%) remaining in the cytosolic fraction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1740413 TI - Role of thrombin exosites in inhibition by heparin cofactor II. AB - We determined the role of specific thrombin "exosites" in the mechanism of inhibition by the plasma serine proteinase inhibitors heparin cofactor II (HC) and antithrombin (AT) in the absence and presence of a glycosaminoglycan by comparing the inhibition of alpha-thrombin to epsilon- and gamma T-thrombin (produced by partial proteolysis of alpha-thrombin by elastase and trypsin, respectively). All of the thrombin derivatives were inhibited in a similar manner by AT, either in the absence or presence of heparin, which confirmed the integrity of both heparin binding abilities and serpin reactivities of epsilon- and gamma T-thrombin compared to alpha-thrombin. Antithrombin activities of HC in the absence of a glycosaminoglycan with alpha-, epsilon, and gamma T-thrombin were similar with rate constants of 3.5, 2.4, and 1.2 x 10(4) M-1 min-1, respectively. Interestingly, in the presence of glycosaminoglycans the maximal inhibition rate constants by HC with heparin and dermatan sulfate, respectively, were as follows: 30.0 x 10(7) and 60.5 x 10(7) for alpha-thrombin, 14.6 x 10(7) and 24.3 x 10(7) for epsilon-thrombin, and 0.017 x 10(7) and 0.034 x 10(7) M-1 min-1 for gamma T-thrombin. A hirudin carboxyl-terminal peptide, which binds to anion-binding exosite-I of alpha-thrombin, dramatically reduced alpha-thrombin inhibition by HC in the presence of heparin but not in its absence. We analyzed our results in relation to the recently determined x-ray structure of D-Phe-Pro Arg-chloromethyl ketone-alpha-thrombin (Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R., and Hofsteenge, J. (1989) EMBO J. 8, 3467-3475). Our results suggest that the beta-loop region of anion-binding exosite-I in alpha-thrombin, which is not present in gamma T-thrombin, is essential for the rapid inhibition reaction by HC in the presence of a glycosaminoglycan. Therefore, alpha-thrombin and its derivatives would be recognized and inhibited differently by HC and AT in the presence of a glycosaminoglycan. PMID- 1740414 TI - Incorporation of [32P]orthophosphate into long chains of inorganic polyphosphate within lysosomes of human fibroblasts. AB - When isolated human fibroblast lysosomes are incubated with 4 microM [32P]phosphate at pH 7.0, orthophosphate is transported into lysosomes and is rapidly incorporated into low and high molecular weight products. We have characterized the high molecular weight (HMW) lysosomal material into which [32P]phosphate is incorporated and have found it to consist of long chains of inorganic polyphosphate based on the following observations. 1) greater than 97% of HMW 32P-lysosomal material is converted to [32P]orthophosphate when incubated with 1 N HCl for 20 min at 100 degrees C. 2) Incubation of HMW 32P-lysosomal material at pH 7.0 and 65 degrees C for 96 h results in the formation of [32P]trimetaphosphate, which is known to be produced only from linear chains of polyphosphate under these conditions. 3) HMW 32P-lysosomal material is resistant to degradation by proteinase K, ribonuclease, and deoxyribonuclease and extracts into the aqueous phase during phenol/chloroform extractions. 4) HMW 32P-lysosomal material displays heterogeneous mobility on polyacrylamide gels with most chains ranging in length from 100 to at least 600 phosphate residues. 5) HMW 32P lysosomal material is partially hydrolyzed under alkaline conditions to yield a continuous ladder of polyphosphate species differing by one or several residues in length on polyacrylamide gels. PMID- 1740415 TI - Distinct oxidoresistance phenotype of human T47D cells transfected by rat glutathione S-transferase Yc expression vectors. AB - We have investigated the role of a glutathione S-transferase (GST) with inherent peroxidase activity in the cellular defense against lipid peroxidation and free radical-mediated oxidative damage. Stable transfectants of human T47D cells were generated which express recombinant rat GST-Yc from a human cytomegalovirus promoter-based expression vector. Among several GST-Yc transfectants characterized, two of them contained, respectively, 2- and 3-fold higher GST activity than parental cells or control transfectants and, respectively, 4-5- and 8-10-fold higher selenium-independent glutathione peroxidase activity. Cellular growth kinetics and rates of [3H]thymidine incorporation showed that both transfectants were more resistant to oxidative shocks mediated by cumene hydroperoxide or singlet oxygen generated by photosensitized rose bengal than were T47D cells and control transfectants. In contrast, a T47D transfectant, which expressed high levels of recombinant selenoglutathione peroxidase and showed enhanced resistance to cumene hydroperoxide (Mirault, M.-E., Tremblay, A., Beaudoin, N., and Tremblay, M. J. (1991) J. Biol. Chem. 266, 20752-20760), was as sensitive as parental cells to singlet oxygen. No difference was found in growth sensitivity to 1-h shock treatments with the quinonoid drug daunomycin, irrespective of GST-Yc or selenoglutathione peroxidase overexpression in these cells. PMID- 1740416 TI - Multinuclear NMR studies of intracellular cations in perfused hypertensive rat kidney. AB - We have investigated hypertension-associated alterations in intracellular cations in the kidney by measuring intracellular pH, free Mg2+, free Ca2+, and Na+ concentrations in perfused normotensive and hypertensive rat (8-14 weeks old) kidneys using 31P, 19F, and double quantum-filtered (DQ) 23Na NMR. The effects of both anoxia and ischemia on the 23Na DQ signal confirmed its ability to detect changes in intracellular Na+. However, there was a sizable contribution of the extracellular Na+ to the 23Na DQ signal of the kidney. The intracellular free Ca2+ concentration, measured using 19F NMR and 5,5'difluoro-1,2-bis(2 aminophenoxy)ethane N,N,N',N'-tetraacetic acid, also increased dramatically during ischemia; the increase could be partly reversed by reperfusion. No significant differences were found between normotensive and hypertensive kidneys in the ATP level, intracellular pH, intracellular free Mg2+, and the 23Na DQ signal or in the extent of the extracellular contribution to the 23Na DQ signal. Oxygen consumption rates were also similar for the normotensive (5.02 +/- 0.46 mumol of O2/min/g) and hypertensive (5.47 +/- 0.42 mumol O2/min/g) rat kidneys. The absence of a significant difference in intracellular pH, Na+ concentration, and oxygen consumption between normotensive and hypertensive rat kidneys suggests that an alteration in the luminal Na+/H+ antiport activity in hypertension is unlikely. However, a highly significant increase (64%, p less than 0.01) in free Ca2+ concentration was found in perfused kidneys from hypertensive rats (557 +/- 48 nM, blood pressure = 199 +/- 5 mmHg, n = 6) compared with normotensive rats (339 +/- 21 nM, blood pressure = 134 +/- 6, n = 4) indicating altered renal calcium homeostasis in essential hypertension. An increase in intracellular free Ca2+ concentration without an accompanying change in the intracellular Na+ suggests, among many possibilities, that the Ca2+/Mg(2+)-ATPase may be inhibited in the hypertensive renal tissue. PMID- 1740417 TI - Point mutational analysis of the hamster dihydrofolate reductase minimum promoter. AB - We have shown previously that 48 base pairs (bp) of 5'-flanking sequence are necessary for correct initiation at the major transcriptional start site of the Chinese hamster dihydrofolate reductase (dhfr) gene (Ciudad et al., 1988). As an upstream element, this sequence alone confers 25% of maximum promoter activity. The 5' half of this sequence is particularly well conserved among mammalian species; it contains one Sp1 binding site (GC box) and one CAA element. In the present work, we have analyzed the role of this region by extensive point mutational analysis. Twenty-three dhfr minigene constructs containing 1- or 2 base substitutions in this region of the promoter were tested by measuring their ability to transfect DHFR-deficient Chinese hamster ovary cells to a DHFR+ growth phenotype. Eight mutants, all in or near the GC box, exhibited reduced transfection efficiency. Promoter disfunction in these mutants was confirmed by RNase protection analysis of stable transfectants. Gel retardation experiments showed that mutants affected in the consensus sequence for Sp1 binding were deficient in binding a protein found in nuclear extracts of Chinese hamster ovary cells. Purified human transcription factor Sp1 was also unable to bind a promoter sequence bearing one of these single base substitutions, suggesting that Sp1 itself is involved in dhfr transcription in vivo. We conclude that most single base mutations in the GC box severely cripple or eliminate promoter function by inhibiting binding of transcription factors to this regulatory sequence and that Sp1 is likely to be involved in dhfr transcription in vivo. We also found that the well conserved CAA element is not absolutely necessary for transcription. PMID- 1740418 TI - Epidermal growth factor enhances a microsomal 12-lipoxygenase activity in A431 cells. AB - 12-Hydroxyeicosatetraenoic acid (12-HETE) is formed from arachidonic acid either by 12-lipoxygenase or by a cytochrome P450 monooxygenase. 12-Lipoxygenase is generally localized in the soluble cytosolic fraction, and the cytochrome P450 monooxygenase is a microsomal enzyme. In this study, 12-HETE biosynthesis and the regulation of 12-HETE biosynthesis by epidermal growth factor (EGF) in A431 cells were investigated. 12-HETE was biosynthesized from arachidonic acid by the microsomal fraction of A431 cells, but not by the cytosolic fraction. The formation of 12-HETE was inhibited by 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and caffeic acid. Nordihydroguaiaretic acid at 10(-4) M and 5,8,11,14-eicosatetraynoic acid at 10(-5) M almost completely inhibited its formation. However, the formation of 12-HETE was not affected by the presence of an NADPH-generating system, carbon monoxide, or SKF 525A. The biosynthetic 12 HETE was analyzed by chiral stationary phase high performance liquid chromatography and was highly enriched in (12S)-HETE. We therefore concluded that the enzyme responsible for the formation of (12S)-HETE in the microsomes of A431 cells is a 12-lipoxygenase. The microsomal 12-lipoxygenase of A431 cells belongs to the "leukocyte-type" enzyme as determined by substrate specificity and enzyme kinetics studies. The microsomal 12-lipoxygenase oxygenated linoleic acid much faster than the cytosolic platelet 12-lipoxygenase and is a "self-catalyzed inactivation" enzyme. Treatment of cells with 50 ng/ml EGF significantly induced microsomal 12-lipoxygenase activity. The lag period for the expression of the stimulatory effect of EGF on 12-lipoxygenase activity was approximately 10 h. The stimulatory effect of EGF on 12-lipoxygenase activity was completely blocked by treatment with 35 microM cycloheximide, indicating a requirement for de novo protein biosynthesis. Furthermore, the presence of the endogenous inhibitor of 12 lipoxygenase (which masked (12S)-HETE biosynthesis in intact cells) was identified in the cytosolic fraction of A431 cells. The putative inhibitor was enzyme-selective. It inhibited the leukocyte-type 12-lipoxygenase, but not the "platelet-type" enzyme. PMID- 1740419 TI - Ionic interactions in the nitrogenase complex. Properties of Fe-protein containing substitutions for Arg-100. AB - A series of Azotobacter vinelandii strains have been constructed in which the nitrogenase Fe-protein (Av2) was altered by substitutions for Arg-100. This invariant residue is a likely partner in a salt bridge with the MoFe-protein and, in some species, is the site of reversible regulation by ADP-ribosylation (Pope, M. R., Murrell, S. A., and Ludden, P. W. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3173-3177). Although we find that arginine is the optimum amino acid, other residues in this position could support diazotrophic growth. These results were surprising because Klebsiella pneumoniae Fe-protein substituted by His-100 had been reported to be inactive (Lowery, R. G., Chang, C. L., Davis, L. C., McKenna, M.-C., Stevens, P. J., and Ludden, P. W. (1989) Biochemistry 28, 1206-1212). Two altered Fe-proteins (Av2-R100Y, the tyrosyl form, and Av2-R100H, the histidyl form) were isolated and, in contrast to this earlier report, we found that both had some activity in acetylene reduction. However, both altered proteins exhibited a decreased maximum velocity (35 and 3% of wild type, respectively) and were strongly inhibited by excess MoFe-protein. These adverse activity parameters were also manifest in the increased sensitivity of the altered proteins to inhibition by salts. Indeed, the salt sensitivity of Av2-R100H is so significant that its activity is masked in the normal assay and is easily missed. In addition, for Av2-R100H, substrate reduction is substantially uncoupled from MgATP hydrolysis. These results suggest that substitutions for Arg-100 may decrease the affinity of the Fe-protein for the MoFe-protein prior to electron transfer but increase affinity after electron transfer. Hence, the role of Arg 100 may be to provide the optimum balance in stabilities of these two complexes for maximum efficiency in substrate reduction. PMID- 1740420 TI - Incorporation and distribution of epoxyeicosatrienoic acids into cellular phospholipids. AB - The different regioisomers of epoxyeicosatrienoic acids derived from cytochrome P 450 monooxygenase are readily esterified into phospholipids of mastocytoma cells. Incorporation of 14,15-epoxyeicosatrienoic acid was concentration-dependent, with Km = 1.1 microM and Vmax = 36 pmol/min/10(7) cells. Half-maximal incorporation occurred in 30 min, reaching a steady-state concentration of 470 pmol/10(6) cells. This was slightly lower than the values for arachidonic acid (665 pmol/10(6) cells) or 5-hydroxyeicosatetraenoic acid (554 pmol/10(6) cells). The distribution of 14,15-epoxyeicosatrienoic acid was preferential in the order phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylinositol greater than phosphatidyl serine much greater than neutral lipids plus fatty acids. This contrasted with 5(S)-hydroxyeicosatetraenoic acid, which was distributed primarily into phosphatidylcholine. Fast atom bombardment/tandem mass spectrometry facilitated identification of molecular species containing epoxyeicosatrienoic acids without relying on radioisotopes. Phosphatidylethanolamine plasmalogens with 16:1 or 18:2 at the sn-1 position, or an 18:0 acyl group, and phosphatidylcholine with 16:0 alkyl ether or an acyl group at the sn-1 position incorporated all possible epoxyeicosatrienoic acid regioisomers. Under basal conditions, cells eliminated 14,15-cis epoxyeicosatrienoic acid slowly with a half-life of 34.9 +/- 7 h. Cells stimulated with calcium ionophore A23187 eliminated 14,15-epoxyeicosatrienoic acid rapidly. It was notable that its rate of release from phosphatidylcholine and phosphatidylinositol exceeded that for arachidonic acid. A coenzyme A independent transacylase also catalyzed the transfer of epoxyeicosatrienoic acids from mastocytoma cell membranes into 1-palmitoyl-2-lysophosphatidylcholine. The cellular incorporation, release, and distribution of epoxyeicosatrienoic acids is distinctive and contrasts with most other eicosanoids, suggesting that these compounds may have both autocoid and nonautocoid functions. PMID- 1740421 TI - Natural bovine osteogenin and recombinant human bone morphogenetic protein-2B are equipotent in the maintenance of proteoglycans in bovine articular cartilage explant cultures. AB - Osteogenin and related bone morphogenetic proteins are members of the transforming growth factor-beta superfamily, and were isolated by their ability to induce cartilage and bone formation in vivo. The influence of osteogenin, purified from bovine bone, and of recombinant human bone morphogenetic protein-2B (BMP-2B) has been examined in bovine articular cartilage explants. Both differentiation factors stimulated in a dose-dependent manner the synthesis of proteoglycans and decreased their rate of degradation. At a dose of 30 ng/ml, proteoglycan synthesis was increased to levels observed with either 20 ng/ml insulin-like growth factor I, 10 ng/ml transforming growth factor-beta, or 20% fetal bovine serum. This increase of biosynthetic rates above basal medium levels was observed in young, adolescent, and adult tissues. Analysis of the size of the newly synthesized proteoglycans, the glycosaminoglycan chain size, and the glycosaminoglycan type of explants treated with osteogenin or BMP-2B were very comparable to each other, and to proteoglycans isolated from cartilage treated with either insulin-like growth factor I or fetal bovine serum. These results demonstrate that osteogenin and BMP-2B alone are capable of stimulating and maintaining the chondrocyte phenotype in vitro. PMID- 1740422 TI - Domain 3 of kininogens contains a cell-binding site and a site that modifies thrombin activation of platelets. AB - High and low molecular weight kininogens (HK and LK) are able to bind to platelets to inhibit thrombin binding to and activation of platelets. The heavy chain domain on the kininogens that contains these functions has been determined. Domain 3 (D3) but not domains 1 or 2, completely inhibited 125I-HK binding to platelets (Ki = 24 +/- 7 nM, n = 4). 125I-D3 specifically bound to unstimulated platelets and human umbilical vein endothelial cells. On platelets, it was blocked by unlabeled D3 and HK but not prekallikrein, factor XII, C1s, or C1 inhibitor. Further, one monoclonal antibody (HKH13) directed to kininogens' D3 blocked 125I-HK and 125I-D3 binding to platelets. The binding of 125I-D3 to platelets was fully reversible by addition of 35 molar excess of unlabeled D3. D3 binding to platelets was saturable with an apparent Kd of 39 +/- 8 nM (n = 4) and 1227 +/- 404 binding sites/platelet. D3, like HK and LK, inhibited thrombin induced platelet activation by preventing thrombin binding to platelets. Another monoclonal antibody (HKH12), directed to D3, which did not block HK binding to platelets, reduced HK's ability to inhibit 125I-alpha-thrombin binding. This result suggests that the region on D3 that inhibits 125I-alpha-thrombin binding to platelets is different from that which directly binds to platelets. These studies indicate that D3 of the kininogens contains both a binding region for platelets and endothelial cells and another region that inhibits thrombin-induced platelet activation. PMID- 1740423 TI - In vivo mutational analysis of the NGFI-A zinc fingers. AB - NGFI-A is a mammalian transcription factor that contains zinc fingers similar to those observed in several other proteins, including NGFI-C and Krox-20. To define precisely the DNA binding domain of NGFI-A, we selected mutants using a chimeric transcriptional activator that contains the NGFI-A zinc finger domain sandwiched between the lexA DNA binding domain and the GAL4 transcriptional activating domain. Expression of this lexA-NGFI-A-GAL4 (LAG) trimeric protein in yeast significantly retarded their growth, unlike an activator containing only the lexA and GAL4 components. This suggested that LAG inappropriately regulates genes in yeast that contain NGFI-A binding sites. Yeast that contained LAG reverted to wild-type growth at high frequency by inactivation of LAG. The mutations recovered from these revertants were specifically limited to the 83-residue NGFI A zinc finger domain by requiring that the lexA and GAL4 portions of the LAG chimera remain functional. Nearly all of the 93 mutants obtained contained single missense mutations that mapped within the zinc fingers to residues thought to be important for zinc finger function. Deletion analysis of native NGFI-A verified that residues distant from the zinc fingers do not influence DNA binding, thus establishing the minimal functional DNA binding domain. Interestingly, many zinc finger residues ascribed specific functions by x-ray crystallography were never mutated in yeast, implying that the identity of these residues is not critical. Surprisingly, not all of the mutations tested significantly impaired NGFI-A specific DNA binding, suggesting that the function of these zinc fingers is more diverse than previously recognized. PMID- 1740424 TI - Factor IXa enhances reconstitution of factor VIIIa from isolated A2 subunit and A1/A3-C1-C2 dimer. AB - Heterotrimeric factor VIIIa was reconstituted from isolated A2 subunit and A1/A3 C1-C2 dimer of thrombin-activated human factor VIII in a reaction that was sensitive to pH. Maximal levels of reconstituted factor VIIIa at pH 6.0 were as much as 20-fold greater than were values observed at pH 7.5. The presence of factor IXa and phospholipid resulted in a marked increase in factor VIIIa reconstituted at physiologic pH. However, the resultant factor VIIIa was unstable due to slow proteolysis of the A1 subunit. Factor IXa modified by the active site specific reagent dansyl-glutamyl-glycyl-arginyl-chloromethyl ketone (DEGR-IXa) increased the level of factor VIIIa reconstituted from subunits to a similar extent as was observed for unmodified factor IXa and yielded stable factor VIIIa. This enhancement was saturated above a 1:1 molar ratio of DEGR-IXa to factor VIIIa subunits and could be blocked by an anti-factor IX antibody, suggesting that the DEGR-IXa-dependent increase in factor VIIIa reconstitution correlated with assembly of the factor X-ase complex. At a saturating amount of DEGR-IXa, the level of factor VIIIa reconstitution at pH 7.5 approached values obtained at pH 6.0. Fluorescence polarization measurements indicated that factor VIIIa altered binding of DEGR-IXa to phospholipid. However, neither the A2 subunit nor the A1/A3-C1-C2 dimer alone produced this effect. This result suggested that both A2 and A1/A3-C1-C2 were necessary for association of the cofactor with factor IXa. These results suggest a model in which assembly of the intrinsic factor X ase complex stabilizes factor VIIIa through inhibition of subunit dissociation. PMID- 1740425 TI - Carbonic anhydrase in Escherichia coli. A product of the cyn operon. AB - The product of the cynT gene of the cyn operon in Escherichia coli has been identified as a carbonic anhydrase. The cyn operon also includes the gene cynS, encoding the enzyme cyanase. Cyanase catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. The carbonic anhydrase was isolated from an Escherichia coli strain overexpressing the cynT gene and characterized. The purified enzyme was shown to contain 1 Zn2+/subunit (24 kDa) and was found to behave as an oligomer in solution; the presence of bicarbonate resulted in partial dissociation of the oligomeric enzyme. The kinetic properties of the enzyme are similar to those of carbonic anhydrases from other species, including inhibition by sulfonamides and cyanate. The amino acid sequence shows a high degree of identity with the sequences of two plant carbonic anhydrases. but not with animal and algal carbonic anhydrases. Since carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate diffuses out of the cell faster than it would be hydrated to bicarbonate, the apparent function of the induced carbonic anhydrase is to catalyze hydration of carbon dioxide and thus prevent depletion of cellular bicarbonate. PMID- 1740426 TI - Shuffling of amino acid sequence: an important control in synthetic peptide studies of nucleic acid-binding domains. Binding properties of fragments of a conserved eukaryotic RNA binding motif. AB - We have used synthetic peptides to study a conserved RNA binding motif in yeast poly(A)-binding protein. Two peptides, 45 and 44 amino acids in length, corresponding to amino and carboxyl halves of a 90-amino acid RNA-binding domain in the protein were synthesized. While the amino-terminal peptide had no significant affinity for nucleic acids, the carboxyl-terminal peptide-bound nucleic acids with similar characteristics to that for the entire 577 residue yeast poly(A)-binding protein. In 100 mM NaCl, the latter peptide retained over 50% of the intrinsic binding free energy of the protein, as well as, similar RNA versus DNA binding specificity. However, shuffling of the sequence of this 44 residue peptide had surprisingly little effect on its nucleic acid binding properties suggesting the overriding importance of amino acid composition as opposed to primary sequence. Deletion studies on the 44 residue peptide with the "correct" sequence succeeded in identifying amino acids important for conferring RNA specificity and for increasing our understanding of the molecular basis for nucleic acid binding by synthetic peptides. The shuffled peptide study, however, clearly indicates that considerable caution must be exercised before extrapolating results of structure/function studies on synthetic peptide analogues to the parent protein. PMID- 1740427 TI - Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart. AB - The effects of L-carnitine on myocardial glycolysis, glucose oxidation, and palmitate oxidation were determined in isolated working rat hearts. Hearts were perfused under aerobic conditions with perfusate containing either 11 mM [2-3H/U 14C]glucose in the presence or absence of 1.2 mM palmitate or 11 mM glucose and 1.2 mM [1-14C]palmitate. Myocardial carnitine levels were elevated by perfusing hearts with 10 mM L-carnitine. A 60-min perfusion period resulted in significant increases in total myocardial carnitine from 4376 +/- 211 to 9496 +/- 473 nmol/g dry weight. Glycolysis (measured as 3H2O production) was unchanged in carnitine treated hearts perfused in the absence of fatty acids (4418 +/- 300 versus 4547 +/- 600 nmol glucose/g dry weight.min). If 1.2 mM palmitate was present in the perfusate, glycolysis decreased almost 2-fold compared with hearts perfused in the absence of fatty acids. In carnitine-treated hearts this drop in glycolysis did not occur (glycolytic rates were 2911 +/- 231 to 4629 +/- 460 nmol glucose/g dry weight.min, in control and carnitine-treated hearts, respectively. Compared with control hearts, glucose oxidation rates (measured as 14CO2 production from [U-14C]glucose) were unaltered in carnitine-treated hearts perfused in the absence of fatty acids (1819 +/- 169 versus 2026 +/- 171 nmol glucose/g dry weight.min, respectively). In the presence of 1.2 mM palmitate, glucose oxidation decreased dramatically in control hearts (11-fold). In carnitine-treated hearts, however, glucose oxidation was significantly greater than control hearts under these conditions (158 +/- 21 to 454 +/- 85 nmol glucose/g dry weight.min, in control and carnitine-treated hearts, respectively). Palmitate oxidation rates (measured as 14CO2 production from [1-14C]palmitate) decreased in the carnitine treated hearts from 728 +/- 61 to 572 +/- 111 nmol palmitate/g dry weight.min. This probably occurred secondary to an increase in overall ATP production from glucose oxidation (from 5.4 to 14.5% of steady state myocardial ATP production). The results reported in this study provide direct evidence that carnitine can stimulate glucose oxidation in the intact fatty acid perfused heart. This probably occurs secondary to facilitating the intramitochondrial transfer of acetyl groups from acetyl-CoA to acetylcarnitine, thereby relieving inhibition of the pyruvate dehydrogenase complex. PMID- 1740428 TI - Analysis of a kinetic model for melanin biosynthesis pathway. AB - The kinetic behavior of the melanin biosynthesis pathway from L-tyrosine up to dopachrome has been studied from experimental and simulation assays. The reaction mechanism proposed is based on a single active site of tyrosinase. The diphenolase and monophenolase activities of tyrosinase involve one single (oxidase) and two overlapped (hydroxylase and oxidase) catalytic cycles, respectively. The stoichiometry of the pathway implies that one molecule of tyrosinase must accomplish two turnovers in the hydroxylase cycle for each one in the oxidase cycle. Furthermore, the steady-state rates of dopachrome production and O2 consumption from tyrosine and L-dopa, also fulfill the stoichiometry of the pathway: VO2T/VDCT = 1.5 and VO2T/VDCD = 1.0, where T represents L-tyrosine, DC represents dopachrome, and D represents L-dopa. It has been ascertained by high performance liquid chromatography that in the steady-state, a quantity of dopa is accumulated ([D]ss) which fulfills the constant ratio [D]ss = R[T]0. Taking this ratio into account, an analytical expression has been deduced for the monophenolase activity of tyrosinase. In this expression kcatT congruent to (2/3)k3(K1/K2)R, revealing that kcatT is not a true catalytic constant, since it also depends on equilibrium constants and on the experimental R = 0.057. This low value explains the lower catalytic efficiency of tyrosinase on tyrosine than on dopa, (VmaxT/KmT)/(VmaxD/KmD) congruent to (2/3)R, since a significant portion of tyrosinase is scavenged from the catalytic turnover as dead-end complex EmetT in the steady-state of the monophenolase activity of tyrosinase. PMID- 1740429 TI - Acylpeptide hydrolase: inhibitors and some active site residues of the human enzyme. AB - Acylpeptide hydrolase may be involved in N-terminal deacetylation of nascent polypeptide chains and of bioactive peptides. The activity of this enzyme from human erythrocytes is sensitive to anions such as chloride, nitrate, and fluoride. Furthermore, blocked amino acids act as competitive inhibitors of the enzyme. Acetyl leucine chloromethyl ketone has been employed to identify one active site residue as His-707. Diisopropylfluorophosphate has been used to identify a second active site residue as Ser-587. Chemical modification studies with a water-soluble carbodiimide implicate a carboxyl group in catalytic activity. These results and the sequence around these active site residues, especially near Ser-587, suggest that acylpeptide hydrolase contains a catalytic triad. The presence of a cysteine residue in the vicinity of the active site is suggested by the inactivation of the enzyme by sulfhydryl-modifying agents and also by a low amount of modification by the peptide chloromethyl ketone inhibitor. Ebelactone A, an inhibitor of the formyl aminopeptidase, the bacterial counterpart of eukaryotic acylpeptide hydrolase, was found to be an effective inhibitor of this enzyme. These findings suggest that acylpeptidase hydrolase is a member of a family of enzymes with extremely diverse functions. PMID- 1740430 TI - Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia. AB - Triglyceride turnover in reperfused/ischemic rat hearts was investigated. Hearts were initially perfused under aerobic conditions for a 1-h "pulse" perfusion with 1.2 mM [1-14C]palmitate to label the endogenous lipid pools, followed by a 30-min period of no-flow ischemia or a 10-min period of retrograde perfusion (control). Hearts were then reperfused under aerobic conditions with buffer containing 1.2 mM [9,10-3H]palmitate. All buffers contained 11 mM glucose and 500 microunits/ml insulin. Rates of endogenous triglyceride lipolysis and synthesis were measured during reperfusion, whereas rates of exogenous palmitate oxidation were measured both prior to ischemia and during reperfusion following ischemia. During reperfusion of ischemic hearts, a 20% increase in exogenous fatty acid oxidation rates was seen compared with pre-ischemic rates. Despite an initial burst of endogenous fatty acid oxidation, no acceleration of steady state endogenous triglyceride lipolysis was seen compared with their nonischemic hearts. In contrast, a significant increase in triglyceride synthesis was observed. Triglyceride turnover was also measured in a series of hearts reperfused following ischemia in the absence of exogenous fatty acids. A significant enhancement of functional recovery was seen compared with hearts reperfused with 1.2 mM palmitate. In addition, a significant increase in fatty acid oxidation from endogenous triglyceride lipolysis was observed. We conclude that the heart quickly recovers its ability to oxidize exogenous fatty acids during reperfusion and that although triglyceride lipolysis is not accelerated during reperfusion of ischemic hearts in the presence of 1.2 mM palmitate, a significant increase in triglyceride synthesis does occur. PMID- 1740431 TI - Active-site structural comparison of streptococcal NADH peroxidase and NADH oxidase. Reconstitution with artificial flavins. AB - The apoproteins of the streptococcal NADH peroxidase (H2O2----2H2O) and NADH oxidase (O2----2H2O) stabilize the neutral forms of 6-hydroxy- and 6-mercapto FAD, respectively. The redox behavior of the 6-hydroxy-FAD peroxidase closely mimics that of the native enzyme with both dithionite and NADH. Both oxidase and peroxidase preferentially stabilize the N(1)-protonated p-quinonoid species of 8 mercapto-FAD, and the 8-position of the bound flavin is accessible to solvent in both proteins. The 8-mercapto-FAD peroxidase yields an EH2 spectrum on reduction virtually identical to that seen with 8-mercapto-FAD glutathione reductase, but no distinct EH2.NADH form appears. The dramatic decreases in reactivity at the flavin 2- and 4-positions for both the peroxidase and the oxidase, assessed with the reconstituted 2- and 4-thio-FAD enzymes, suggest that these positions are buried by elements of both protein structures. Furthermore, reconstitution of the peroxidase with the higher potential 2- and 4-thioflavins yields enzyme forms which are fully reducible with 1.4 eq of NADH/FAD, giving rise to stable thio FADH2.NAD+ complexes. This behavior closely mimics that of the native NADH oxidase and provides further evidence supporting the hypothesis that a major functional distinction between the two structurally related proteins is determined by the redox potential and/or NADH reactivity of the bound flavin coenzyme. PMID- 1740432 TI - An analysis of the side chain requirement at position 177 within the lactose permease which confers the ability to recognize maltose. AB - In previous work (Brooker, R. J., and Wilson, T. H. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 3959-3963), lactose permease mutants were isolated which possessed an enhanced recognition for maltose. In some of these mutants, the wild-type alanine residue at position 177 was changed to valine or threonine. To gain further insight into the side chain requirement at position 177 that confers maltose recognition, further substitutions of isoleucine, leucine, phenylalanine, proline, and serine have been made via site-directed mutagenesis. Permeases containing alanine or serine exhibited poor maltose recognition whereas those containing isoleucine, leucine, phenylalanine, proline, or valine showed moderate or good recognition. As far as galactosides are concerned, the Val-177, Pro-177, and Ser-177 mutants were able to transport lactose as well as, or slightly better than, the wild-type strain. The other mutants displayed moderately reduced levels of lactose transport. For example, the Phe-177 mutant, which was the most defective, showed a level of downhill transport which was approximately 20% that of the wild-type strain. In uphill transport assays, all of the position 177 mutants were markedly defective in their ability to accumulate beta-D thiomethylgalactopyranoside against a concentration gradient. Finally, the position 177 mutants were analyzed for their ability to catalyze an H+ leak. Interestingly, even though the wild-type permease does not leak H+ across the bacterial membrane, all of the position 177 mutants were shown to transport H+ in the absence of sugars. For most of the mutants, this H+ leak was blocked by the addition of beta-D-thiodigalactoside. Overall, these results are discussed with regard to the effects of position 177 substitutions on the sugar recognition site and H+ transport. PMID- 1740433 TI - Identification of novel members of the serum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein. AB - A novel serum amyloid A protein (SAA) has been identified as a normal apolipoprotein component of non-acute phase high density lipoprotein. This novel SAA has been designated "constitutive" SAA (C-SAA) to distinguish it from "acute phase" SAA (A-SAA). C-SAA was partially sequenced, and immunochemical analyses indicated that it constitutes a distinct subclass of apolipoproteins within the SAA superfamily. A C-SAA cDNA clone was isolated from a human liver library and sequenced. The clone predicts a pre-C-SAA molecule of 130 residues from which an 18-residue leader peptide is cleaved. The 112-residue mature molecule is 8 residues longer than human A-SAA; the size difference is due to the presence of an octapeptide between positions 70 and 77 that is not found in the corresponding region of human A-SAA. Paradoxically, octapeptides of similar composition are found at similar positions in the A-SAAs of a number of other species. The C-SAA octapeptide specifies the first two residues of a NSS tripeptide, the only potential N-linked glycosylation site in the molecule. Studies indicate that approximately 50% of these sites are glycosylated, thereby giving rise to two size classes, 14 and 19 kDa, of C-SAA in vivo. Human acute phase liver contains little C-SAA mRNA relative to the levels of A-SAA mRNA, and the treatment of PLC/PRF/5 hepatoma cells with monocyte-conditioned medium does not induce C-SAA mRNA concentrations to detectable levels, in contrast to the massive induction of A-SAA mRNA observed. C-SAA is therefore not a major acute phase reactant. PMID- 1740434 TI - Multiple endoglycosidase (Endo) F activities expressed by Flavobacterium meningosepticum. Endo F1: molecular cloning, primary sequence, and structural relationship to Endo H. AB - A full-length insert for the endo-beta-N-acetylglucosaminidase (Endo) F1 gene was located on a 2,200-base pair EcoRI fragment of genomic DNA and cloned into the plasmid vector Bluescript. Transformed Escherichia coli cells expressed Endo F1 activity very well, but the enzyme apparently was not processed and secreted into the medium as it normally is in Flavobacterium meningosepticum. DNA sequencing revealed an open reading frame of 1,017 nucleotides encoding a putative 50-amino acid signal sequence, and a mature protein (31,667 Da) of 289 amino acids. The deduced amino acid sequence was verified by direct Edman microsequencing of 88% of the purified protein as tryptic and V8 protease peptides. Alignment of Endo F1 (289 amino acids) with the established amino acid sequence of Streptomyces plicatus Endo H (271 amino acids) revealed a 32% structural identity over the entire sequence and a high degree of conservative replacements. Potential catalytic domains identified in other proteins that hydrolyze the beta 1,4 glycosidic linkage between N-acetylglucosamine residues are also conserved for amino acid identity and relative spacing in Endo F1. PMID- 1740435 TI - Expression of rat liver glutamine transporters in Xenopus laevis oocytes. AB - As a first step in attempting to isolate the Na(+)-dependent System N transporter from rat liver we have investigated the use of prophase-arrested oocytes from Xenopus laevis for the functional expression of rat liver glutamine transporters. Individual oocytes, defolliculated by collagenase treatment, were injected with 50 nl of a 1 mg.ml-1 solution of poly(A)+ RNA (mRNA) isolated from rat liver. 50 microM L-[3H]glutamine uptake was measured 1-5 days post-injection: after 48 h, poly(A)+ RNA-injected oocytes showed a 60 +/- 12% increase in Na(+)-dependent glutamine uptake compared to controls. This increased uptake showed characteristic features of hepatic System N: that is, it tolerated Li(+)-for-Na+ substitution and was inhibited by the System N substrate L-histidine (5 mM) in Li medium, unlike endogenous Na(+)-dependent glutamine transport. In subsequent experiments rat liver poly(A)+ RNA, size-fractionated by density gradient fractionation, was injected into oocytes. Injection of poly(A)+ RNA of 1.9-2.8 kilobases (kb) in size resulted in a significant stimulation of Na(+)-dependent glutamine transport to 0.362 +/- 0.080 pmol.min-1/oocyte from 0.178 +/- 0.060 pmol.min-1/oocyte in vehicle-injected oocytes (p less than 0.01). A lighter fraction, with poly(A)+ RNA of less than 1.9 kilobases size resulted in a similar increase in Na(+)-dependent glutamine uptake which was largely Li(+)-tolerant: Li(+)-stimulated glutamine uptake in oocytes injected with this fraction increased to 0.230 +/- 0.070 pmol.min-1/oocyte from 0.098 +/- 0.029 pmol.min 1/oocyte in controls (p less than 0.05). This enhanced rate of Li(+)-stimulated glutamine uptake was inhibited 28 and 70%, respectively, by 1 and 5 mM L histidine. Na(+)-independent uptake of glutamine rose by 72 +/- 12% in oocytes injected with poly(A)+ RNA of 2.8-3.6 kb (p less than 0.001). These results demonstrate that glutamine transporters, with characteristics associated with hepatic Systems N, L, and A (or ASC), can be expressed in X. laevis oocytes injected with specific size fractions of rat liver mRNA. PMID- 1740436 TI - Identification of an essential tyrosine residue in the catalytic site of a chitinase isolated from Zea mays that is selectively modified during inactivation with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. AB - Chitinase isolated from Zea mays seeds is inactivated by 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDC) in the absence of exogenous nucleophiles. Oligomers of N-acetylglucosamine,N,N',N",N"'-tetra-N-acetylchitotetraose (GlcNAc4), and to a lesser extent, N,N',N"-tri-N-acetylchitotriose (GlcNAc3) and N,N'-di-N-acetylchitobiose (GlcNAc2) provide partial protection against inactivation by the reagent. An examination of the concentration dependence of the protection afforded by GlcNAc4 revealed direct competition between the substrate analog and the reagent for the same binding sites on the enzyme. Isolation and Edman degradation of a "new" tryptic fragment, observed after inactivation of chitinase with EDC, revealed the sequence G-P-L-Q-I-S-W-N-*-N-Y-G P-A-G-R, where the asterisk represents a cycle in which no amino acid was detected, presumably as a consequence of derivatization with EDC. In basic chitinases from dicotyledonous plants such as Arabidopsis thaliana, Phaseolis vulgaris (bean), Nicotiana tabacum (tobacco), and Solanum tuberosum (potato), as well as in the chitinase isolated from the monocotyledonous plant Hordeum vulgare (barley), this position is invariably occupied by a tyrosine. However, in the Oryza sativa (rice) basic chitinase, this position is occupied by a phenylalanine. The following additional evidence supports identification of this residue as tyrosine in Z. mays chitinase. (a) Inactivation of chitinase with EDC is reversible by treatment with hydroxylamine. (b) Liquid secondary ion mass spectrometric analysis of the isolated derivatized peptide revealed the presence of a molecular ion with a mass to charge ratio consistent with the peptide containing a derivatized tyrosine residue. These results provide evidence for an essential tyrosine residue at or near the catalytic site of chitinase that is selectively modified during inactivation with EDC. PMID- 1740437 TI - Molecular cloning of the major cell surface heparan sulfate proteoglycan from rat liver. AB - We have used an antiserum raised against a purified heparan sulfate proteoglycan (HSPG) preparation isolated from rat liver to screen a lambda gt11 expression library and have obtained overlapping cDNA clones that contain the full-length coding sequence of an HSPG core protein capable of spanning the plasma membrane. The open reading frame of the rat cDNA encodes a protein of 211 amino acids. The predicted protein sequence (23 kDa) has a high degree of homology with the published partial sequence of the human lung fibroblast HSPG, fibroglycan. The deduced protein sequence contains a 24-amino acid transmembrane domain and a 33 amino acid cytoplasmic domain, both of which are identical with the corresponding regions of human fibroglycan and are highly homologous to the human, hamster, and mouse epithelial HSPG, syndecan. The putative ectodomain, which has 85% homology to fibroglycan, contains three possible glycosaminoglycan attachment sites that may be occupied by heparan sulfate chains. The major 49-kDa core protein in the liver HSPG preparation was found to be reactive to an antibody that specifically recognizes the cytoplasmic domain of fibroglycan. We have used the full-length cDNA clone to analyze the expression of this transmembrane core protein gene in whole tissues and several epithelial and fibroblastoid cell lines. It hybridizes to three mRNA species in all cell and tissue types examined, but in liver, isolated hepatocytes, and kidney, an additional 0.8-kilobase mRNA was detected. The three common messages arise from differential use of alternative polyadenylation sites, whereas the fourth tissue-restricted RNA species represents a related gene transcript. The rat equivalent of human fibroglycan therefore appears to be the major transmembrane proteoglycan in liver, and its widespread expression in many diverse tissues and cells suggests that it plays an important role in cellular interactions. PMID- 1740438 TI - Sex-specific, growth hormone-regulated transcription of the cytochrome P450 2C11 and 2C12 genes. AB - Growth hormone (GH) differentially regulates the expression of several male specific and female-specific liver cytochrome P450 mRNAs as a function of its sex dependent ultradian secretory pattern. Pulsatile GH release stimulates expression of the male-specific P450 2C11, while a continuous GH secretion pattern suppresses expression of 2C11 and stimulates the expression of the female specific P450 2C12. To help define the level at which GH regulates the expression of 2C11 and 2C12 mRNA, liver nuclear RNA samples isolated from rats differing in GH status were analyzed for 2C11 and 2C12 hnRNAs by hybridization to 2C11 and 2C12 gene-specific exonic oligonucleotide probes, as well as exon/intron junction probes. The 2C11 and 2C12 hnRNAs were found to be responsive to circulating GH profiles in a manner indistinguishable from the corresponding mature, cytoplasmic mRNAs, with no 2C12 mRNA precursors found in untreated male or hypophysectomized female liver nuclei, and no 2C11 mRNA precursors in untreated female or hypophysectomized male liver nuclei. Thus, transport of 2C11 and 2C12 RNA to the cytoplasm and cytoplasmic mRNA stability are unlikely to be important GH regulated control points for sex-specific P450 RNA expression. Run-on transcription analysis further established that GH regulates the sex-specific expression of the 2C11 and 2C12 genes at the level of transcript initiation. Transcription was also shown to be the major step for regulation of the male specific P450 2A2 RNA, whose expression, unlike 2C11, is not obligatorily dependent on pulsatile GH release. In vitro footprinting analysis of 2C11 and 2C12 promoter fragments incubated with liver nuclear proteins isolated from rats differing in GH status revealed several sex- and GH-dependent differences in DNase cleavage patterns ("hypersensitivity sites"), demonstrating that GH can regulate specific protein-DNA interactions in the 5'-flanking sequences of these two genes. In vitro transcription assays driven by 2C11 and 2C12 5'-flanking DNA sequences fused to TATAA box-G-less cassette template constructs did not, however, faithfully mimic the sex-specific transcription of the 2C11 and 2C12 genes, indicating that additional cis-elements or trans-acting factors may be required to achieve the transcriptional regulation of these genes that occurs in vivo. PMID- 1740439 TI - Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Male specificity of liver and kidney CYP4A2 mRNA and tissue-specific regulation by growth hormone and testosterone. AB - The induction of liver cytochrome P450 4A-catalyzed fatty acid omega-hydroxylase activity by clofibrate and other peroxisome proliferators has been proposed to be causally linked to the ensuing proliferation of peroxisomes in rat liver. Since female rats are less responsive than males to peroxisome proliferation induced by clofibrate, the influence of gender and hormonal status on the basal and clofibrate-inducible expression of the 4A P450s was examined. Northern blot analysis using gene-specific oligonucleotide probes revealed that in the liver, P450 4A1 and 4A3 mRNAs are induced to a much greater extent in male as compared to female rats following clofibrate treatment, whereas P450 4A2 mRNA is altogether absent from female rat liver. Male-specific expression of P450 4A2 mRNA was also observed in kidney. Western blot analysis indicated that a similar sex dependence characterizes both the basal expression and the clofibrate inducibility of the corresponding P450 4A proteins. This suggests that the lower responsiveness of female rats to clofibrate-induced peroxisome proliferation may reflect the lower inducibility of the P450 4A fatty acid hydroxylase enzymes in this sex. Investigation of the contribution of pituitary-dependent hormones to the male-specific expression of 4A2 revealed that this P450 mRNA is fully suppressed in liver following exposure to the continuous plasma growth hormone profile that characterizes adult female rats; in this and other regards liver P450 4A2 is regulated in a manner that is similar, but not identical to, P450 3A2, a male-specific testosterone 6 beta-hydroxylase. In contrast, kidney 4A2 expression, although also male-specific, was not suppressed by continuous growth hormone treatment, but was regulated by pathways that, in part, involve testosterone as a positive regulator. The male-specific expression of liver and kidney P450 4A2 is thus under the control of distinct pituitary-dependent hormones acting in a tissue-specific manner. PMID- 1740440 TI - Myristoylation of proteins in the yeast secretory pathway. AB - Protein myristoylation was investigated in the yeast secretory pathway. Conditional secretory mutations were used to accumulate inteRmediaries in the pathway between the endoplasmic reticulum and Golgi (sec 18, 20), within the Golgi (sec 7), and between the Golgi and plasma membrane (sec 1, 3, 4, 5, 6, 8, 9). The accumulation of vesicles was paralleled by the enrichment of a defined subset of proteins modified either via ester or amide linkages to myristic acid: Myristoylated proteins of 21, 32, 49, 56, 75, and 136 kDa were enriched between the endoplasmic reticulum and Golgi; proteins of 21, 32, 45, 56, 75, 136 kDa were enriched by blocks within the Golgi; and proteins of 18, 21, 32, 36, 49, 68, and 136 kDa were trapped in a myristoylated form by blocks between the Golgi and plasma membrane. This enrichment of myristoylated proteins was reversed upon returning the cells to the permissive temperature for secretion. The fatty acid was linked to the 21-kDa protein via a hydroxylamine-resistant amide linkage (N myristoylation) and to the proteins of 24, 32, 49, 56, 68, 136 kDa via hydroxylamine-labile ester linkage (E-myristoylation). In addition, myristoylated proteins of 21, 56, and 136 kDa were glycosylated via amino linkages to asparagine. This suggests they are exposed to the lumen of the secretory pathway. Three proteins (24, 32, and 56) were E-myristoylated in the presence of protein synthesis inhibitors, indicating this modification can occur posttranslationally. After using cycloheximide to clear protein passengers from the secretory pathway the 21-, 32-, and 56-kDa proteins continued to accumulate in a myristoylated form when vesicular transport was blocked between the Golgi and plasma membrane. These data suggest that myristoylation occurs on a component of the secretory machinery rather than on a passenger protein. PMID- 1740441 TI - Demonstration of a calcium requirement for secretory protein processing and export. Differential effects of calcium and dithiothreitol. AB - HepG2 cells were employed as model system to investigate potential relationships between early protein processing and Ca2+ storage by the endoplasmic reticulum. Ca2+ was required for glycoprotein processing and export by intact cells. The processing and export of alpha 1-antitrypsin and the secretion of complement factor 3, which are glycosylated proteins, were inhibited by the Ca2+ ionophore ionomycin whereas the export of albumin, a non-glycoprotein, was little affected. Ionomycin blocked processing of alpha 1-antitrypsin at the conversion from the high mannose to the complex glycosylated form without affecting ATP or GTP contents. Pre-existing inhibition of intracellular processing of alpha 1 antitrypsin by ionomycin was fully reversible upon removal of the ionophore with fatty acid-free bovine serum albumin. This reversal required Ca2+. After reversal the arrested form of alpha 1-antitrypsin was fully converted to the mature form and exported to the medium. Inhibitions of alpha 1-antitrypsin processing and complement factor 3 secretion by the metalloendoprotease antagonist Cbz-Gly-Phe NH2 (where Cbz is benzyloxycarbonyl) were strongest at low extracellular Ca2+ but were reduced or prevented by high extracellular Ca2+. Processing and secretion of alpha 1-antitrypsin were reduced upon incubation in low Ca2+ medium. Exposure to dithiothreitol reduced albumin export while affecting alpha 1-antitrypsin export minimally. Suppression of amino acid incorporation into total cellular proteins of HepG2 cells accompanied inhibitions of protein processing by agents depleting sequestered Ca2+ stores or by dithiothreitol. Putative control of rates of translational initiation by the endoplasmic reticulum through linkage to rates of early protein processing is discussed. PMID- 1740442 TI - rab GTP-binding proteins with three different carboxyl-terminal cysteine motifs are modified in vivo by 20-carbon isoprenoids. AB - p21ras and several other ras-related GTP-binding proteins are modified post translationally by addition of 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenoids to cysteines within a conserved carboxyl-terminal sequence motif, Caa(M/S/L), where a is an aliphatic amino acid. Proteins ending with M or S are substrates for farnesyltransferase, whereas those ending with L are modified preferentially by geranylgeranyltransferase. We recently reported that GTP binding proteins encoded by rab1B (GGCC), rab2 (GGCC), and rab5 (CCSN) are modified by 20-carbon isoprenyl derivatives of [3H]mevalonate when translated in vitro, despite having carboxyl-terminal sequences distinct from the Caa(M/S/L) motif. We now show that these proteins function as specific acceptors for geranylgeranyl in vitro and are modified by 20-carbon isoprenyl groups in COS cells metabolically labeled with [3H]mevalonate. Proteins encoded by rab4 and rab6, with yet another distinct carboxyl-terminal motif (xCxC), are similarly modified by 20-carbon isoprenoids in vitro and in vivo. The geranylgeranyl modification of rab5 protein (CCSN) is catalyzed by an enzyme in brain cytosol but not by a purified geranylgeranyltransferase that modifies GTP-binding proteins with the CaaL motif. Unlike the prenylation of proteins with Caa(M/S/L) termini, the prenylation of rab5 protein is not inhibited by a synthetic peptide based on its carboxyl-terminal sequence (TRNQCCSN). When cellular isoprenoid synthesis is blocked by treatment of cells with lovastatin, rab proteins that are normally localized in membranes of the endoplasmic reticulum, Golgi apparatus, and endosomes accumulate in the cytosol. This change in rab protein localization is reversed by providing cells with mevalonate. These findings suggest that geranylgeranyl modification underlies the ability of rab GTP-binding proteins to associate with intracellular membranes, where they are postulated to function as mediators of vesicular traffic. PMID- 1740443 TI - Extracellular autoprocessing of a metalloprotease from Streptomyces cacaoi. AB - We have previously demonstrated that the extracellular neutral metalloprotease (Npr) of Streptomyces cacaoi is synthesized as a 60-kDa preproenzyme (P60), then processed to the 35-kDa mature form (P35) (Chang, P. C., Kuo, T.-C., Tsugita, A., and Lee, Y.-H. W. (1990) Gene (Amst.) 88, 87-95). In this study, we investigated the active site and the mechanism involved in the maturation of the protease. Site-specific mutations at the putative zinc-binding ligands and active site of Npr at His202, Glu203, His206, and Glu240 led to complete abolishment of Npr activity and concomitant accumulation of a 57-kDa inactive protein (P57) which was secreted. Sequence analysis of the NH2 terminus indicated that P57 was derived from P60 after removal of the signal peptide and represented the proenzyme form of Npr (pro-Npr). Analysis of the zinc content of purified mutant P57 proteins revealed a dramatic loss of zinc atom as compared with the wild-type P35 protein. In vitro with the aid of exogenous active Npr, the mutant P57 protein could be converted to the mature inactive P35 with an identical NH2 terminal sequence and a molecular mass the same as that of the wild-type P35. From these studies, we conclude that these highly conserved residues (His202, Glu203, His206, and Glu240) are indispensable for zinc binding and protease activity, as well as processing of Npr. In addition, we have clearly demonstrated that maturation of Npr occurs extracellularly via an autocatalytic cleavage of the pro-Npr propeptide. This is the first report of such a maturation mechanism for an extracellular protease in streptomycetes which can serve as a model for further studies on the mechanism of secretion and processing of proteases from Gram-positive bacteria. PMID- 1740444 TI - Alternative splicing of fructose 1,6-bisphosphate aldolase transcripts in Drosophila melanogaster predicts three isozymes. AB - The genes that encode fructose 1,6-bisphosphate aldolase of Drosophila melanogaster have been isolated and characterized. These genes exist in a single copy 8-kilobase pair locus in the Drosophila genome which is located at cytogenetic position 97A-B. The nucleotide sequence and transcript mapping suggest that three overlapping protein isozyme genes may be encoded at this locus. These isozyme genes all share a single promoter, a 5'-untranslated first exon, and two other protein coding exons. The isozyme-specific carboxyl-terminal amino acids are encoded by one of three alternatively utilized fourth exons: 4A, 4B, or 4C by alternative splicing. The transcript containing exon 4C, whose sequence has been reported previously, is abundant throughout development and has a developmental profile similar to other glycolytic gene transcripts; however, it shows developmental specificity in the alternative use of two polyadenylation signals which result in a 2.4-kilobase and a 1.9-kilobase transcript. The transcript containing exon 4B is 1.6 kilobases in size and is most abundant during the larval stages and during the time of eclosion. The transcript containing exon 4A is in low abundance and found only during the adult stage. Sequence comparisons of the alternative fourth exons indicate that the duplication leading to the multiple exons is quite old and preceded the origin of the genus Drosophila. PMID- 1740445 TI - A novel 40-kDa membrane-associated EF-hand calcium-binding protein in Plasmodium falciparum. AB - A 40-kDa sexual stage radiolabeled surface protein of Plasmodium falciparum, Pfs40, was previously identified as a potential target antigen of transmission blocking immunity by an immunogenetic approach. Synthetic oligonucleotide "guessmers," based on microsequenced tryptic peptides of Pfs40 purified by two dimensional gel electrophoresis, were used to clone the full length cDNA and genomic DNA encoding Pfs40. The deduced amino acid sequence predicted an integral membrane protein containing five EF-hand calcium-binding domains. The biological activity of one or more of these domains was confirmed by binding of 45Ca to both native and recombinant Pfs40. Antisera to recombinant Pfs40 immunoprecipitated the native radiolabeled 40-kDa surface protein. The predicted noncytosolic membrane-associated localization of Pfs40 is unique within the EF-hand calcium binding protein superfamily. PMID- 1740446 TI - Translocation of ATP into the lumen of rough endoplasmic reticulum-derived vesicles and its binding to luminal proteins including BiP (GRP 78) and GRP 94. AB - Rat liver and canine pancreas rough endoplasmic reticulum-derived vesicles, which were sealed and of the same topographical orientation as in vivo, were used in a system in vitro to demonstrate translocation of ATP into their lumen. Translocation of ATP is saturable (apparent Km: 3-4 microM and Vmax: 3-7 pmol/min/mg of protein) and protein mediated because treatment of intact vesicles with Pronase, N-ethylmaleimide, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibit transport. The entire ATP molecule is being translocated; this was shown by high performance liquid chromatography analysis and the use of a nonhydrolyzable analog. Control experiments rule out that translocation of ATP attributed to rough endoplasmic reticulum-derived vesicles is due to contamination by mitochondria and Golgi vesicles. Following translocation of ATP into the lumen of the vesicles, binding to luminal proteins including BiP (immunoglobulin heavy chain-binding protein-glucose-regulated protein 78) and glucose-regulated protein 94 was observed. This binding appeared to be specific because similar experiments with GTP were negative. These studies strongly suggest that translocation of ATP into the rough endoplasmic reticulum lumen may serve as a mechanism for making ATP available in proposed energy requiring reactions within the lumen. PMID- 1740447 TI - Structural relationships between two forms of DNA polymerase epsilon from calf thymus. AB - We previously reported purification of two forms of DNA polymerase epsilon from calf thymus (Crute, J. J., Wahl, A. F., and Bambara, R. A. (1986) Biochemistry 25, 26-36). We have now used the "polymerase trap" photolabeling method to identify the polypeptides containing the polymerase active site in each enzyme preparation. The molecular mass of these polypeptides are 210 and 145 kDa for the polymerases now designated epsilon and epsilon*, respectively. Renaturation of polymerase activity from denaturing gel electrophoresis corroborates the polymerase trap results. Photolabeling of polymerase fractions suggests that the smaller subunit is derived by proteolysis of the larger subunit during purification. Native sedimentation coefficient measurements of polymerase containing column fractions further suggest a precursor/product relationship between the two polymerases. Response of polymerization activity to a battery of inhibitors normally used to distinguish mammalian nuclear DNA polymerases was found to be essentially identical for polymerases epsilon, epsilon*, and the epsilon* generated in fractions initially containing epsilon. These latter results demonstrate that the loss of the protease-sensitive domain of the active site subunit does not affect catalytic function as measured in a standard DNA polymerase assay. The sole apparent functional difference observed here between the epsilon and epsilon* forms is evidence that only the full-length epsilon form can be directly photocrosslinked to dATP, independent of DNA synthesis. Photolabeling of the post-microsomal supernatant fraction from thymus glands obtained from fetal calves reveals the presence of both the epsilon and epsilon* polypeptide. PMID- 1740448 TI - Molecular cloning and characterization of the structural gene coding for the developmentally regulated lysosomal enzyme, alpha-mannosidase, in Dictyostelium discoideum. AB - The gene coding for the Dictyostelium discoideum lysosomal enzyme, alpha mannosidase, has been cloned and sequenced. To accomplish this, the mature 60- and 58-kDa subunits of the enzyme were purified and subjected to liquid-phase N terminal amino acid sequencing. Sequence information was obtained for both of the mature subunits, and a 48-mer oligonucleotide was synthesized based on the determined amino acid sequence of the 58-kDa subunit. Using this oligonucleotide as a probe, an 8-kilobase HindIII fragment of genomic DNA was isolated and subjected to Sanger dideoxy DNA sequencing. The first 4400 nucleotides contained the complete alpha-mannosidase gene and 1100 nucleotides of 5'-flanking DNA. Primer extension analysis indicated that transcription begins at multiple sites 48 to -64 nucleotides upstream of the first nucleotide of the predicted translation initiation codon. A single open reading frame (ORF) of 3015 nucleotides was found that was interrupted by a single intron and that contained the amino acid sequences of the N termini of the two mature alpha-mannosidase subunits; a polyadenylation signal was also found just downstream of the termination codon. A potential cleavable signal sequence was identified in the first 22 amino acids of the predicted precursor protein, and two propeptide regions (Pro I and II) were identified that were immediately upstream of the N termini of the 60- and 58-kDa mature subunits, respectively. These propeptide regions are not present in the mature protein and are therefore predicted to be proteolytically removed as the membrane associated 140-kDa precursor is transported to lysosomes and processed to the soluble 60- and 58-kDa mature forms of the enzyme. In fact, potential proteolytic cleavage sites were identified flanking the Pro I and Pro II regions. Pro I, which immediately follows the signal sequence, consists of 18 amino acids, most of which are highly charged and hydrophilic residues, while Pro II, found in the central portion of the precursor, is very hydrophobic. While no obvious transmembrane regions were identified, several short hydrophobic amino acid stretches were found to be localized in and around the Pro II region, and these may be responsible for attachment of precursors to membranes. PMID- 1740449 TI - Alternative splicing and endoproteolytic processing generate tissue-specific forms of pituitary peptidylglycine alpha-amidating monooxygenase (PAM). AB - The pituitary is a rich source of peptidylglycine alpha-amidating monooxygenase (PAM). This bifunctional protein contains peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalytic domains necessary for the two-step formation of alpha-amidated peptides from their peptidylglycine precursors. In addition to the four forms of PAM mRNA identified previously, three novel forms of PAM mRNA were identified by examining anterior and neurointermediate pituitary cDNA libraries. None of the PAM cDNAs found in pituitary cDNA libraries contained exon A, the 315-nucleotide (nt) segment situated between the PHM and PAL domains and present in rPAM-1 but absent from rPAM-2. Although mRNAs of the rPAM-3a and -3b type encode bifunctional PAM precursors, the proteins differ significantly. rPAM-3b lacks a 54-nt segment encoding an 18-amino acid peptide predicted to occur in the cytoplasmic domain of this integral membrane protein; rPAM-3a lacks a 204-nt segment including the transmembrane domain and encodes a soluble protein. rPAM-5 is identical to rPAM-1 through nt 1217 in the PHM domain; alternative splicing generates a novel 3' region encoding a COOH-terminal pentapeptide followed by 1.1 kb of 3' untranslated region. The soluble rPAM-5 protein lacks PAL, transmembrane, and cytoplasmic domains. These three forms of PAM mRNA can be generated by alternative splicing. The major forms of PAM mRNA in both lobes of the pituitary are rPAM-3b and rPAM-2. Despite the fact that anterior and neurointermediate pituitary contain a similar distribution of forms of PAM mRNA, the distribution of PAM proteins in the two lobes of the pituitary is quite different. Although integral membrane proteins similar to rPAM-2 and rPAM-3b are major components of anterior pituitary granules, the PAM proteins in the neurointermediate lobe have undergone more extensive endoproteolytic processing, and a 75-kDa protein containing both PHM and PAL domains predominates. The bifunctional PAM precursor undergoes tissue-specific endoproteolytic cleavage reminiscent of the processing of prohormones. PMID- 1740450 TI - Genomic organization of mouse J kappa recombination signal binding protein (RBP-J kappa) gene. AB - We have isolated a cDNA clone (RBP-2) for the protein (RBP-J kappa) which binds to immunoglobulin recombination signals with 23-base pair spacers (Matsunami, N., Hamaguchi, Y., Yamamoto, Y., Kuze, K., Kangawa, K., Matsuo, H., Kawaichi, M., and Honjo, T. (1989) Nature 342, 934-937). During further screening of a cDNA library from the same mouse pre-B cell line (38B9), we have isolated a second cDNA clone (RBP-2N) which differs from RBP-2 in its 5' sequence. RNase protection assays indicated that the RBP-2N type mRNA was produced in 10-20 times the quantity as RBP-2 mRNA. To elucidate the relationship between these two mRNAs, we analyzed the genomic organization of the RBP-J kappa gene. Southern hybridization of mouse genomic DNA detected at least 7 EcoRI fragments hybridizing to an RBP-2 cDNA probe, suggesting a complex structure for the RBP-J kappa gene. Cloning of each EcoRI fragment revealed one functional RBP-J kappa gene and three related genes. The functional gene was composed of 11 exons and spanned at least 50 kilobase pairs. The sequence of exon 1 and its 5'-flanking region contained a GC-rich promoter-like region but no apparent TATA box. The initiation site of transcription was heterogeneous, and the two types of mRNA are produced from the same exon by transcription initiation at different sites and by different usage of splice signals. Two of the three related genes were processed pseudogenes with scattered stop codons. The other was also a processed gene with a sequence exactly the same as that of RBP-2, except that this gene lacked the sequence corresponding to the first exon of the functional gene. PMID- 1740451 TI - Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA replication fork. I. Multiple effectors act to modulate Okazaki fragment size. AB - The coordinated action of many enzymatic activities is required at the DNA replication fork to ensure the error-free, efficient, and simultaneous synthesis of the leading and lagging strands of DNA. In order to define the essential protein-protein interactions and model the regulatory pathways that control Okazaki fragment synthesis, we have reconstituted the replication fork of Escherichia coli in vitro in a rolling circle-type DNA replication system. In this system, in the presence of the single-stranded DNA binding protein, the helicase/primase function on the lagging-strand template is provided by the primosome, and the synthesis of DNA strands is catalyzed by the DNA polymerase III holoenzyme. These reconstituted replication forks synthesize equivalent amounts of leading- and lagging-strand DNA, move at rates comparable to those measured in vivo (600-800 nucleotides/s at 30 degrees C), and can synthesize leading strands in the range of 150-500 kilobases in length. Using this system, we have studied the cycle of Okazaki fragment synthesis at the replication fork. This cycle is likely to have several well defined decision points, steps in the cycle where incorrect execution by the enzymatic machinery will result in an alteration in the product of the reaction, i.e. in the size of the Okazaki fragments. Since identification of these decision points should aid in the determination of which of the enzymes acting at the replication fork control the cycle, we have endeavored to identify those reaction parameters that, when varied, alter the size of the Okazaki fragments synthesized. Here we demonstrate that some enzymes, such as the DnaB helicase, remain associated continuously with the fork while others, such as the primase, must be recruited from solution each time synthesis of an Okazaki fragment is initiated. We also show that variation of the concentration of the ribonucleoside triphosphates and the deoxyribonucleoside triphosphates affects Okazaki fragment size, that the control mechanisms acting at the fork to control Okazaki fragment size are not fixed at the time the fork is assembled but can be varied during the lifetime of the fork, and that alteration in the rate of the leading-strand DNA polymerase cannot account for the effect of the deoxyribonucleoside triphosphates. PMID- 1740452 TI - Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA replication fork. II. Frequency of primer synthesis and efficiency of primer utilization control Okazaki fragment size. AB - To investigate the role of the priming apparatus at the replication fork in determining Okazaki fragment size, the products of primer synthesis generated in vitro during rolling-circle DNA replication catalyzed by the DNA polymerase III holoenzyme, the single-stranded DNA binding protein, and the primosome on a tailed form II DNA template were isolated and characterized. The abundance of oligoribonucleotide primers and the incidence of covalent DNA chain extension of the primer population was measured under different reaction conditions known to affect the size of the products of lagging-strand DNA synthesis. These analyses demonstrated that the factors affecting Okazaki fragment length could be distinguished by either their effect on the frequency of primer synthesis or by their influence on the efficiency of initiation of DNA synthesis from primer termini. Primase and the ribonucleoside triphosphates were found to stimulate primer synthesis. The observed trend toward smaller fragment size as the concentration of these effectors was raised was apparently a direct consequence of the increased frequency of primer synthesis. The beta subunit of the DNA polymerase III holoenzyme and the deoxyribonucleoside triphosphates did not alter the priming frequency; instead, the concentration of these factors influenced the ability of the lagging-strand DNA polymerase to efficiently utilize primers to initiate DNA synthesis. Maximum utilization of the available primers correlated with the lowest mean value of Okazaki fragment length. These data were used to draw general conclusions concerning the temporal order of enzymatic steps that operate during a cycle of Okazaki fragment synthesis on the lagging-strand DNA template. PMID- 1740453 TI - Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA replication fork. V. Primase action regulates the cycle of Okazaki fragment synthesis. AB - Replication forks formed during rolling-circle DNA synthesis supported by a tailed form II DNA substrate in the presence of the primosome, the single stranded DNA binding protein, and the DNA polymerase III holoenzyme (Pol III HE) that had been reconstituted from the purified subunits, beta, tau, and the gamma.delta complex, at limiting (with respect to nucleotide incorporation) concentrations of the Pol III core (alpha, epsilon, and theta) produced aberrantly small Okazaki fragments, while the synthesis of the leading strand was unperturbed. These small Okazaki fragments were not arrayed in tandem along the lagging-strand DNA template, but were separated by large gaps. Similarly structured synthetic products were not manufactured by replication forks reconstituted with higher, saturating concentrations of the Pol III core. Replication forks producing these small fragments could respond, by modulating the size of the Okazaki fragments produced, to variations in the concentration of NTPs or the primase, conditions that affect the frequency of priming on the lagging strand, but not to variation in the concentration of dNTPs, conditions that affect the frequency of utilization of the primers. Significantly longer Okazaki fragments (greater than 7 kilobases) could be produced in the presence of a limiting amount of Pol III core at low concentrations of the primase. These observations indicated that the production of small Okazaki fragments was not a result of a debilitated lagging-strand Pol III core, but rather a function of the time available for nascent strand synthesis during the cycle of events that are required for the manufacture of an Okazaki fragment and that it was the association of primase with the replication fork that keyed this cycle. PMID- 1740454 TI - Chromogranin B (secretogranin I), a secretory protein of the regulated pathway, is also present in a tightly membrane-associated form in PC12 cells. AB - Chromogranin B (CgB, also called secretogranin I) is a secretory protein sorted to secretory granules in a wide variety of endocrine cells and neurons. Unexpectedly, after stimulation of regulated secretion in the neuroendocrine cell line PC12, a fraction of the exocytosed CgB was not released into the medium but remained associated with the plasma membrane. The addition of exogenous CgB to unstimulated cells did not result in the appearance of cell surface CgB, suggesting that the presence of cell surface CgB could not be accounted for by adsorption of released CgB to the cell surface. Upon further incubation of stimulated PC12 cells, the surface CgB was internalized by the cells and largely degraded. The surface CgB was not released by exposure to pH 11, yet it partitioned in the aqueous phase upon Triton X-114 phase separation. Subcellular fractionation and differential extraction studies showed that the membrane associated CgB constituted at least 10% of the total cellular CgB. These observations suggest that (a) the appearance of CgB at the cell surface is due to fusion of secretory granules with the plasma membrane and (b) a fraction of CgB is present in tight association with the secretory granule membrane. We propose a model in which membrane-associated CgB, by virtue of its ability to interact in a homophilic manner with soluble CgB, plays a key role in the sorting and targeting of CgB to the regulated pathway. PMID- 1740455 TI - COQ2 is a candidate for the structural gene encoding para hydroxybenzoate:polyprenyltransferase. AB - Coenzyme Q functions as a lipid-soluble electron carrier in eukaryotes. In Saccharomyces cerevisiae, the enzymes responsible for the assembly of the polyisoprenoid side chain and subsequent transfer to para-hydroxybenzoate (PHB) are encoded by the nuclear genes COQ1 and COQ2, respectively. Yeast mutants defective in coenzyme Q biosynthesis are respiratory defective and provide a useful tool to study this non-sterol branch of the isoprenoid biosynthetic pathway. We isolated a 5.5-kilobase genomic DNA fragment that was able to functionally complement a coq2 strain. Additional complementation analyses located the COQ2 gene within a 2.1-kilobase HindIII-BglII restriction fragment. Sequence analyses revealed the presence of a 1,116-base pair open reading frame coding for a predicted protein of 372 amino acids and a molecular mass of 41,001 daltons. The amino acid sequence exhibits a typical amino-terminal mitochondrial leader sequence and six potential membrane-spanning domains. Primer extension and Northern analyses indicate the gene is transcriptionally active. Transformation of a coq2 strain with the 2.1-kilobase HindIII-BglII genomic restriction fragment on a multicopy plasmid restores PHB:polyprenyltransferase activity to wild-type levels. Disruption of the chromosomal COQ2 gene indicates the gene is not essential for viability, yet is required for PHB:polyprenyltransferase activity and respiratory function. In addition, the deduced amino acid sequence of PHB:polyprenyltransferase contains a putative allylic polyprenyl diphosphate binding site. The presence of this aspartate-rich domain in a number of functionally distinct proteins which utilize polyprenyl diphosphate substrates is reported. PMID- 1740456 TI - Evidence for separate networks of classical and novel basement membrane collagen. Characterization of alpha 3(IV)-alport antigen heterodimer. AB - The COOH-terminal non-collagenous domains (NC1) of type IV collagen from glomerular basement membranes (GBM), lens capsule basement membranes, and Descemet's membrane varied in the distribution of their NC1 subunits. All of these basement membranes (BMs) contained both classical (alpha 1(IV) and alpha 2(IV)) and novel collagen chains (alpha 3(IV), alpha 4(IV) and the Alport antigen). Whereas GBM had a predominance of disulfide-bonded subunits, the lens capsule and Descemet's membrane were primarily monomeric, differences that are likely related to the functional and structural diversity of collagen in various tissues. A heterodimer formed from monomeric subunits of alpha 3(IV) and the Alport antigen exists in human and bovine GBM. This dimer represents an important cross-link of the NC1 domain of novel collagen. Additionally, immunoaffinity methodology showed that the novel BM collagen hexamers segregate into populations containing only novel BM subunits without the participation of the classical subunits (alpha 1(IV) and alpha 2(IV)). These data provided evidence for the presence of two separate networks of BM collagen: one containing alpha 1(IV) and alpha 2(IV), and the other consisting of the novel collagen chains. PMID- 1740457 TI - Isolation of a novel human alpha (1,3)fucosyltransferase gene and molecular comparison to the human Lewis blood group alpha (1,3/1,4)fucosyltransferase gene. Syntenic, homologous, nonallelic genes encoding enzymes with distinct acceptor substrate specificities. AB - Biochemical and genetic evidence indicates that the human genome may encode four or more distinct GDP-fucose:beta-D-N-acetylglucosaminide 3-alpha-L fucosyltransferase (alpha(1,3)fucosyltransferase) activities. Genes encoding two of these activities have been previously isolated. These correspond to an alpha(1,3/1,4)fucosyltransferase thought to represent the human Lewis blood group locus and an alpha(1,3)fucosyltransferase expressed in the myeloid lineage. We report here the molecular cloning and expression of a third human alpha(1,3)fucosyltransferase gene, homologous to but distinct from the two previously reported human fucosyltransferase genes. When expressed in transfected mammalian cells, this gene determines expression of a fucosyltransferase capable of using N-acetyllactosamine to form the Lewis x epitope, and alpha(2,3)sialyl-N acetyllactosamine to construct the sialyl Lewis x moiety. This enzyme shares 91% amino acid sequence identity with the human Lewis blood group alpha(1,3/1,4)fucosyltransferase, yet exhibits only trace amounts of alpha(1,4)fucosyltransferase activity. Polymerase chain reaction analyses were used to demonstrate that the gene is syntenic to the Lewis locus on chromosome 19. These analyses also excluded the possibility that this DNA segment represents an allele of the Lewis locus that encodes alpha(1,3)fucosyltransferase but not alpha(1,4)fucosyltransferase activity. These results are consistent with the hypothesis that this gene encodes the human "plasma type" alpha(1,3)fucosyltransferase, and suggest a molecular basis for a family of human alpha(1,3)fucosyltransferase genes. PMID- 1740458 TI - Covalent binding of C3b to C4b within the classical complement pathway C5 convertase. Determination of amino acid residues involved in ester linkage formation. AB - C5 convertase of the classical complement pathway is a protein complex consisting of C4b, C2a, and C3b. Within this complex C3b binds to C4b via an ester linkage. We now present evidence that the covalent C3b-binding site on human C4b is Ser at position 1217 of C4. We also show that formation of the covalently linked C4b.C3b complex occurs in the mouse complement system and that the C3b-binding site on mouse C4b is Ser at position 1213 which is homologous to Ser-1217 of human C4. Therefore, covalent binding of C3b to a single specific site on C4b within the classical pathway C5 convertase is likely a common phenomenon in the mammalian complement system. Specific noncovalent association of metastable C3b with C4b would occur first, leading to reaction of the thioester with a specific hydroxy group. This is supported by two lines of experimental evidence, one which shows that a mutant C4 that does not make a covalent linkage with C3b is still capable of forming C5 convertase and a second in which the C4b.C3b complex has been demonstrated by cross-linking erythrocytes bearing this C5 convertase. PMID- 1740459 TI - C1 repressor of phage P1 is inactivated by noncovalent binding of P1 Coi protein. AB - The temperate phage P1 encodes two genes whose products antagonize the action of the phage's C1 repressor of lytic functions, namely a distantly linked antirepressor gene, ant, and a closely linked c1 inactivator gene, coi. Starting with an inducible coi-recombinant plasmid, Coi protein was overproduced and purified to near homogeneity. By using a DNA mobility shift assay we demonstrate that Coi protein inhibits the operator binding of the C1 repressors of the closely related P1 and P7 phages. Coi protein (Mr = 7,600) exerts its C1 inactivating function by forming a complex with the C1 repressor (Mr = 32,500) at a molar ratio of about 1:1, as shown by density gradient centrifugation and gel filtration. C1 repressor and Coi protein are recovered in active form from the complex, suggesting that noncovalent interactions are the sole requirements for complex formation. The interplay of repressor and antagonists operating in the life cycle of P1 is discussed. PMID- 1740460 TI - Deletion analysis of recombinant human factor V. Evidence for a phosphatidylserine binding site in the second C-type domain. AB - Human coagulation factor V is an integral component of the prothrombinase complex. Rapid activation of prothrombin is dependent on the interactions of this nonenzymatic cofactor with factor Xa and prothrombin in the presence of calcium ions and a phospholipid or platelet surface. Factor V is similar structurally and functionally to the homologous cofactor, factor VIII, which interacts with factor IXa to accelerate factor X activation in the presence of calcium and phospholipids. Both of these cofactors, when activated, possess homologous heavy and light chains. Binding to anionic phospholipids is mediated by the light chains of these two cofactors. In bovine factor Va, a phosphatidylserine-specific binding site has been localized to the amino-terminal A3 domain of the light chain. In human factor VIII, on the other hand, a region within the carboxyl terminal C2 domain of the light chain has been shown to interact with anionic phospholipids. We have constructed a series of recombinant deletion mutants lacking domain-size fragments of the light chain of human factor V (rHFV). These mutants are expressed and secreted as single-chain proteins by COS cells. Thrombin and the factor V activator from Russell's viper venom process these deletion mutants as expected. The light chain deletion mutants possess essentially no procoagulant activity, nor are they activated by treatment with factor V activator from Russell's viper venom. Deletion of the second C-type domain results in essentially complete loss of phosphatidylserine-specific binding whereas the presence of the C2 domain alone (rHFV des-A3C1, which lacks the A3 and C1 domains of the light chain) results in significant phosphatidylserine-specific binding. The presence of the A3 domain alone (rHFV des-C1C2) does not mediate binding to immobilized phosphatidylserine. Increasing calcium ion concentrations result in decreased binding of recombinant human factor V and the mutant rHFV des-A3C1 to phosphatidylserine, similar to previous studies with purified plasma factor V and phospholipid vesicles. These results indicate that human factor V, similar to human factor VIII, possesses a phosphatidylserine-specific binding site within the C2 domain of the light chain. PMID- 1740461 TI - Putative three-stranded DNA pairing intermediate in recA protein-mediated DNA strand exchange: no role for guanine N-7. AB - As an early step in DNA strand exchange reactions, the recA protein aligns homologous sequences within two DNA molecules to form a putative triple-stranded intermediate. In virtually all models for three-stranded DNA proposed to date, hydrogen bonds involving the N-7 position of guanine have played a prominent structural role. To determine whether the N-7 position of guanine is required for triple helix and heteroduplex formation in the recA protein-mediated DNA pairing reaction, guanine was completely replaced by the base analog 7-deazaguanine in both strands of the duplex DNA substrate using polymerase chain reaction. This modified double-strand DNA was reacted with unmodified single-strand DNA in vitro. The 7-deazaguanine-substituted DNA functioned as well as the unsubstituted DNA in recA protein-mediated DNA three-strand exchange reactions. Strand exchange reactions involving four strands also proceeded normally when three of the four strands contained 7-deazaguanine rather than guanine. In fact, the rate of strand exchange improved somewhat when the modified DNA substrates were used. This indicates either that the N-7 position of guanine is not essential for the formation of the putative triple-stranded DNA pairing intermediate, or that a three-stranded (or four-stranded) structure is not an obligate intermediate in recA protein-mediated DNA strand exchange. PMID- 1740462 TI - The intracellular targeting and membrane topology of 3-hydroxy-3-methylglutaryl CoA reductase. AB - We present evidence that the amino-terminal 39 residue region of 3-hydroxy-3 methylglutaryl- (HMG) CoA reductase, which includes the putative first transmembrane span, is a signal sequence for targeting HMG-CoA reductase to the endoplasmic reticulum. This evidence is based upon fractionation, endoglycosidase H sensitivity and protease protection assays on an in vitro transcription/translocation system programmed with a mutant cDNA of HMG-CoA reductase that is deleted for sequences coding for all of the putative transmembrane spans except the first. We show that the protein product of this mutant cDNA is associated with microsomes, glycosylated, or protected from proteolysis only in the presence of Signal Recognition Particle. Also, we present evidence for a topological model of HMG-CoA reductase that consists of eight transmembrane spans. This evidence is based upon a concanavalin A binding assay for in vivo glycosylation of an engineered glycosylation site in each of a series of mutants of the fusion protein, HMGal (Skalnik, D. G., Narita, H., Kent, C., and Simoni, R. D. (1988) J. Biol. Chem. 263, 6836-6841). This series of mutants was designed such that for each linker segment between transmembrane spans, a mutant was constructed with an engineered glycosylation site introduced into that linker segment. We show that only the mutants with glycosylation sites in the linker segments between transmembrane spans 1 and 2, 3 and 4, and 5 and 6 are glycosylated. These results support an eight transmembrane span model for the topology of HMG-CoA reductase and are inconsistent with a seven-transmembrane span model. PMID- 1740463 TI - The role of the membrane domain in the regulated degradation of 3-hydroxy-3 methylglutaryl coenzyme A reductase. AB - We have constructed a series of mutations in the membrane and linker domains of Syrian hamster 3-hydroxy-3-methylglutaryl-(HMG) CoA reductase in order to determine the regions critical for the regulated degradation of the enzyme. In transfected Chinese hamster ovary cells, we have expressed a fusion protein, HMGal, which consists of the membrane and linker domains of the Syrian hamster HMG-CoA reductase fused to beta-galactosidase. Using this fusion protein, we have determined that a deletion of 64 amino acids from the central region of the membrane domain causes the protein to be degraded extremely rapidly. In addition, deletion of PEST sequences has little effect on degradation, but deletion of the linker domain makes the protein's degradation insensitive to sterols and mevalonate. In addition to deletion mutations, we have systematically replaced each hydrophobic, putative membrane spanning region of the membrane domain with the first transmembrane sequence from bacteriorhodopsin. Replacement of span 4 has no effect on degradation. Replacements of spans 5 or 6 result in a protein which has a normal basal rate of degradation, but this rate of degradation is not accelerated by mevalonate, low density lipoprotein, or 25-hydroxycholesterol. Replacement of span 3 results in a protein whose degradation is similarly not accelerated by sterols or mevalonate, but since this protein might be mislocalized, these results are inconclusive. Replacement of span 7 yields a short-lived protein which is degraded more rapidly in response to mevalonate but not in response to exogenous sterols. Replacement of span 8 extends both the basal and mevalonate-accelerated half-life about 5-fold. This work begins to define the critical regions for regulated degradation within the membrane domain of HMG-CoA reductase. PMID- 1740464 TI - Fine mapping of the high molecular weight kininogen binding site on blood coagulation factor XI through the use of rationally designed synthetic analogs. AB - Using immunological and chemical cleavage techniques, we have previously identified a domain contained within residues Phe56-Ser86 in the first tandem repeat (A1) of the heavy chain of factor XI which binds high Mr kininogen (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1990) J. Biol. Chem. 265, 4149 4154). We have now chemically synthesized peptides from corresponding homologous regions in the second (A2), third (A3), and fourth (A4) tandem repeats of the heavy chain (A2: Asn145-Ala176; A3: Asn235-Arg266; and A4: Gly326-Lys357). These peptides had no effect on the binding of factor XI to high Mr kininogen. Because of a lack of detailed structural information for the A1 domain, a molecular model of this region was constructed. This hypothetical model made distinct and testable predictions regarding potential surfaces and concomitant secondary structure. Specifically, the resulting structure depicted two juxtaposed beta stranded stem-loops that, in conjunction with biological information, constitute a candidate surface for contact with high Mr kininogen. The hypothetical A1 model was, consequently, used as a predictive template in the rational design of two synthetic peptides (Val59-Arg70 and Asn72-Lys83). When both these peptides were added together and the binding of factor XI to high Mr kininogen was examined, a synergistic inhibitory effect was observed compared with each peptide added individually. Our data are consistent with the notion that the sequence of amino acids from Val59-Lys83 of the heavy chain of factor XI contains two antiparallel beta-strands connected by beta-turns that together comprise a continuous surface utilized for the binding of high Mr kininogen. PMID- 1740465 TI - Refinement of the structure of recombinant rat intestinal fatty acid-binding apoprotein at 1.2-A resolution. AB - The three-dimensional structure of the 131-residue rat intestinal fatty acid binding protein, without bound ligand (apoI-FABP), has been refined with x-ray diffraction data to a nominal resolution of 1.19 A. The final model has a conventional crystallographic R-factor of 16.9% for 34,290 unique reflections [a root mean square (r.m.s.) deviation for bond length of 0.012 A and a r.m.s. deviation of 2.368 degrees for bond angles]. Ninety-two residues are present as components of the protein's 10 anti-parallel beta-strands while 14 residues are part of its two short alpha-helices. The beta-strands and alpha-helices are organized into two nearly orthogonal beta-sheets. Particular attention has been placed in defining solvent structure and the structures of discretely disordered groups in this protein. Two hundred thirty-seven solvent molecules have been identified; 24 are located within apoI-FABP. The refined model includes alternate conformers for 228 protein atoms (109 main-chain, 119 side-chain) and 63 solvent molecules. We have found several aromatic side-chains with multiple conformations located near, or in, the protein's ligand binding site. This observation, along with the fact that these side-chains have a temperature factor that is relatively higher than that of other aromatic residues, suggests that they may be involved in the process of noncovalent binding of fatty acid. The absence of a true hydrophobic core in I-FABP suggests that its structural integrity may be maintained primarily by a hydrogen bonding network involving protein and solvent atoms. PMID- 1740466 TI - Brefeldin A: insights into the control of membrane traffic and organelle structure. PMID- 1740467 TI - Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere. AB - We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha-satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres. PMID- 1740468 TI - Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. AB - Five distinct patterns of DNA replication have been identified during S-phase in asynchronous and synchronous cultures of mammalian cells by conventional fluorescence microscopy, confocal laser scanning microscopy, and immunoelectron microscopy. During early S-phase, replicating DNA (as identified by 5 bromodeoxyuridine incorporation) appears to be distributed at sites throughout the nucleoplasm, excluding the nucleolus. In CHO cells, this pattern of replication peaks at 30 min into S-phase and is consistent with the localization of euchromatin. As S-phase continues, replication of euchromatin decreases and the peripheral regions of heterochromatin begin to replicate. This pattern of replication peaks at 2 h into S-phase. At 5 h, perinucleolar chromatin as well as peripheral areas of heterochromatin peak in replication. 7 h into S-phase interconnecting patches of electron-dense chromatin replicate. At the end of S phase (9 h), replication occurs at a few large regions of electron-dense chromatin. Similar or identical patterns have been identified in a variety of mammalian cell types. The replication of specific chromosomal regions within the context of the BrdU-labeling patterns has been examined on an hourly basis in synchronized HeLa cells. Double labeling of DNA replication sites and chromosome specific alpha-satellite DNA sequences indicates that the alpha-satellite DNA replicates during mid S-phase (characterized by the third pattern of replication) in a variety of human cell types. Our data demonstrates that specific DNA sequences replicate at spatially and temporally defined points during the cell cycle and supports a spatially dynamic model of DNA replication. PMID- 1740469 TI - Mechanisms responsible for F-actin stabilization after lysis of polymorphonuclear leukocytes. AB - While actin polymerization and depolymerization are both essential for cell movement, few studies have focused on actin depolymerization. In vivo, depolymerization can occur exceedingly rapidly and in a spatially defined manner: the F-actin in the lamellipodia depolymerizes in 30 s after chemoattractant removal (Cassimeris, L., H. McNeill, and S. H. Zigmond. 1990. J. Cell Biol. 110:1067-1075). To begin to understand the regulation of F-actin depolymerization, we have examined F-actin depolymerization in lysates of polymorphonuclear leukocytes (PMNs). Surprisingly, much of the cell F-actin, measured with a TRITC-phalloidin-binding assay, was stable after lysis in a physiological salt buffer (0.15 M KCl): approximately 50% of the F-actin did not depolymerize even after 18 h. This stable F-actin included lamellar F-actin which could still be visualized one hour after lysis by staining with TRITC-phalloidin and by EM. We investigated the basis for this stability. In lysates with cell concentrations greater than 10(7) cells/ml, sufficient globular actin (G-actin) was present to result in a net increase in F-actin. However, the F-actin stability was not solely because of the presence of free G-actin since addition of DNase I to the lysate did not increase the F-actin loss. Nor did it appear to be because of barbed end capping factors since cell lysates provided sites for barbed end polymerization of exogenous added actin. The stable F-actin existed in a macromolecular complex that pelleted at low gravitational forces. Increasing the salt concentration of the lysis buffer decreased the amount of F-actin that pelleted at low gravitational forces and increased the amount of F-actin that depolymerized. Various actin-binding and cross-linking proteins such as tropomyosin, alpha-actinin, and actin-binding protein pelleted with the stable F actin. In addition, we found that alpha-actinin, a filament cross-linking protein, inhibited the rate of pyrenyl F-actin depolymerization. These results suggested that actin cross-linking proteins may contribute to the stability of cellular actin after lysis. The activity of crosslinkers may be regulated in vivo to allow rapid turnover of lamellipodia F-actin. PMID- 1740470 TI - Mechanism of centrosome positioning during the wound response in BSC-1 cells. AB - Locomoting cells are characterized by a pronounced external and internal anterior posterior polarity. One of the events associated with cell polarization at the onset of locomotion is a shift of the centrosome, or MTOC, ahead of the nucleus. This position is believed to be of strategic importance for directional cell movement and cell polarity. We have used BSC-1 cells at the edge of an in vitro wound to clarify the causal relationship between MTOC position and the initiation of cell polarization. We find that pronounced cell polarization (the extension of a lamellipod) can take place in the absence of MTOC repositioning or microtubules. Conversely, MTOCs will reposition even after lamellar extension and cell polarization have occurred. Repositioning requires microtubules that extend to the cell periphery and is independent of selective detyrosination of microtubules extending towards the cell front. Significantly, MTOCs maintain, or at least attempt to maintain, a position at the cell's centroid. This is most clearly demonstrated in wounded monolayers of enucleated cells where the MTOC closely follows the centroid position. We suggest that the primary response to the would is the biased extension of a lamellipod, which can occur in the absence of microtubules and MTOC repositioning. Lamellipod extension leads to a shift of the cell's centroid towards the wound. The MTOC, in an attempt to maintain a position near the cell center, will follow. This will automatically put the MTOC ahead of the nucleus in the vast majority of cells. The nucleus as a reference for MTOC position may not be as meaningful as previously thought. PMID- 1740471 TI - Meiotic spindle assembly in Drosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like protein. AB - Mature Drosophila oocytes are arrested in metaphase of the first meiotic division. We have examined microtubule and chromatin reorganization as the meiosis I spindle assembles on maturation using indirect immunofluorescence and laser scanning confocal microscopy. The results suggest that chromatin captures or nucleates microtubules, and that these subsequently form a highly tapered spindle in which the majority of microtubules do not terminate at the poles. Nonexchange homologs separate from each other and move toward opposite poles during spindle assembly. By the time of metaphase arrest, these chromosomes are positioned on opposite half spindles, between the metaphase plate and the spindle poles, with the large nonexchange X chromosomes always closer to the metaphase plate than the smaller nonexchange fourth chromosomes. Nonexchange homologs are therefore oriented on the spindle in the absence of a direct physical linkage, and the spindle position of these chromosomes appears to be determined by size. Loss-of-function mutations at the nod locus, which encodes a kinesin-like protein, cause meiotic loss and nondisjunction of nonexchange chromosomes, but have little or no effect on exchange chromosome segregation. In oocytes lacking functional nod protein, most of the nonexchange chromosomes are ejected from the main chromosomal mass shortly after the nuclear envelope breaks down and microtubules interact with the chromatin. In addition, the nonexchange chromosomes that are associated with spindles in nod/nod oocytes show excessive poleward migration. Based on these observations, and the structural similarity of the nod protein and kinesin, we propose that nonexchange chromosomes are maintained on the half spindle by opposing poleward and anti-poleward forces, and that the nod protein provides the anti-poleward force. PMID- 1740472 TI - The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. AB - Specific interactions between desmoplakins I and II (DP I and II) and other desmosomal or cytoskeletal molecules have been difficult to determine in part because of the complexity and insolubility of the desmosome and its constituents. We have used a molecular genetic approach to investigate the role that DP I and II may play in the association of the desmosomal plaque with cytoplasmic intermediate filaments (IF). A series of mammalian expression vectors encoding specific predicted domains of DP I were transiently expressed in cultured cells that form (COS-7) and do not form (NIH-3T3) desmosomes. Sequence encoding a small antigenic peptide was added to the 3' end of each mutant DP cDNA to facilitate immunolocalization of mutant DP protein. Light and electron microscopical observations revealed that DP polypeptides including the 90-kD carboxy-terminal globular domain of DP I specifically colocalized with and ultimately resulted in the complete disruption of IF in both cell lines. This effect was specific for IF as microtubule and microfilament networks were unaltered. This effect was also specific for the carboxyl terminus of DP, as the expression of the 95-kD rod domain of DP I did not visibly alter IF networks. Immunogold localization of COS 7 cells transfected with constructs including the carboxyl terminus of DP demonstrated an accumulation of mutant protein in perinuclear aggregates within which IF subunits were sequestered. These results suggest a role for the DP carboxyl terminus in the attachment of IF to the desmosome in either a direct or indirect manner. PMID- 1740473 TI - Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect. AB - The PKC1 gene of Saccharomyces cerevisiae encodes a homologue of the Ca(2+) dependent isozymes of mammalian protein kinase C (Levin, D.cE., F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner. 1990. Cell. 62:213-224). Cells depleted of the PKC1 gene product display a uniform phenotype, a behavior indicating a defect in the cell division cycle (cdc). These cells arrest division after DNA replication, but before mitosis. Unlike most cdc mutants, which continue to grow in the absence of cell division, PKC1-depleted cells arrest growth with small buds. We created conditional alleles of PKC1 to explore the nature of this unusual cdc defect. In contrast to PKC1-depleted cells, all of the conditional pkc1 mutants isolated were suppressed by the addition of CaCl2 to the medium, suggesting that the mutant enzymes could be activated by Ca2+. Arrest of growth and cell division in the conditional mutants was accompanied by cessation of protein synthesis, rapid loss of viability, and release of cellular material into the medium, suggesting cell lysis. This conclusion was supported by the observation that a pkc1 deletion mutant was capable of proliferation in osmotically stabilized medium, but underwent rapid cell lysis when shifted to hypo-osmotic medium. We have incorporated these observations into a model to explain the cdc-specific arrest of pkc1 mutants. PMID- 1740474 TI - The plus ends of stable microtubules are the exclusive nucleating structures for microtubules in the axon. AB - Microtubules (MTs) in the axon have a uniform polarity orientation that is recapitulated during recovery from episodes of MT depolymerization (Heidemann, S. R., M. A. Hamborg, S. J. Thomas, B. Song, S. Lindley, and D. Chu. 1984. J. Cell Biol. 99:1289-1295). This tight regulation of their organization indicates that axonal MTs are spatially regulated by discrete nucleating structures comparable in function to the centrosome. Several authors have proposed that an especially stable class of MTs in the axon may serve as these nucleating structures. In a previous report (Baas, P. W., and M. M. Black. 1990. J. Cell Biol. 111:495-509), we determined that the axons of cultured sympathetic neurons contain two classes of MT polymer, stable and labile, that differ in their sensitivity to nocodazole by roughly 35-fold. The stable and labile polymer represent long-lived and recently assembled polymer, respectively. We also determined that these two classes of polymer can be visually distinguished at the immunoelectron microscopic level based on their content of tyrosinated alpha-tubulin: the labile polymer stains densely, while the stable polymer does not stain. In the present study, we have taken advantage of these observations to directly identify MT nucleating structures in the axon. Neuron cultures were treated with nocodazole for 6 h to completely depolymerize the labile polymer in the axon, and substantially shorten the stable polymer. The cultures were then rinsed free of the drug, permitted to reassemble polymer for various periods of time, and prepared for immunoelectron microscopic localization of tyrosinated alpha tubulin. Serial reconstruction of consecutive thin sections was undertaken to determine the spatial relationship between the stable MTs and the newly assembled polymer. All of the new polymer assembled in direct continuity with the plus ends of stable MTs, indicating that these ends are assembly competent, and hence capable of acting as nucleating structures. Our results further indicate that no self-assembly of MTs occurs in the axon, nor do any MT nucleating structures exist in the axon other than the plus ends of stable MTs. Thus the plus ends of stable MTs are the exclusive nucleating structures for MTs in the axon. PMID- 1740475 TI - Incorporation of protein into spore coats is not cell autonomous in Dictyostelium. AB - At maturity, the spores of Dictyostelium are suspended in a viscous fluid droplet, with each spore being surrounded by its own spore coat. Certain glycoproteins characteristic of the spore coat are also dissolved in this fluid matrix after the spore coat is formed. To determine whether any proteins of the coat reside in this fluid phase earlier during the process of spore coat assembly, pairs of strains which differed in a spore coat protein carbohydrate marker were mixed and allowed to form spore coats in each other's presence. We reasoned that proteins belonging to an early, soluble, extracellular pool would be incorporated into the spore coats of both strains. To detect trans incorporation, spores were labeled with a fluorescent antibody against the carbohydrate marker and each spore's fluorescence was analyzed by flow cytometry. Several proteins of both the outer and inner protein layers of the coat appeared to be faithfully and reciprocally trans-incorporated and hence judged to belong to a soluble, assembly-phase pool. Western blot analysis of sorted spores, and EM localization, confirmed this conclusion. In contrast, one outer-layer protein was not trans-incorporated, and was concluded to be insoluble at the time of secretion. Three classes of spore coat proteins can be described: (a) Insoluble from the time of secretion; (b) present in the early, soluble pool but not the late pool after spore coat formation; and (c) present in the soluble pool throughout spore coat assembly. These classes may, respectively: (a) Nucleate spore coat assembly; (b) comprise a scaffold defining the dimensions of the nascent spore coat; and (c) complete the assembly process by intercalation into the scaffold. PMID- 1740476 TI - Clinical review 31: Anabolic-androgenic steroids and athletes: what are the issues? PMID- 1740477 TI - New biomarkers of bone resorption. PMID- 1740478 TI - Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. AB - Osteoclastic activity is increased in tumor-associated hypercalcemia, which, thus, constitutes an excellent opportunity to assess new markers of the bone resorption rate. We have measured the fasting urinary excretion of the pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) in 36 hypercalcemic cancer patients (mean +/- SD, 3.2 +/- 0.4 mmol/L for total serum Ca and 1.66 +/- 0.24 mmol/L for Ca2+). Thirty-two of them were reevaluated after treatment with iv bisphosphonates. Urinary Pyr and D-Pyr levels were higher than those in healthy controls (130 +/- 62 vs. 40 +/- 19 nmol/mmol creatinine for Pyr and 20 +/ 15 vs. 6 +/- 3 nmol/mmol creatinine for D-Pyr; P less than 0.001 for both). This represented a mean 3.3-fold increase over the normal mean compared to 5.8- and 3.4-fold increases for fasting urinary Ca and hydroxyproline, respectively. Individual values were elevated in 83% and 75% of the cases for Pyr and D-Pyr compared to 97% and 83% for urinary Ca and hydroxyproline, respectively. The levels of Pyr and D-Pyr tended to be higher in patients with head and neck tumors than in patients with breast cancer. Urinary Pyr and D-Pyr correlated with each other (r = 0.72; P less than 0.001) and were highly correlated with hydroxyproline (r = 0.68 and 0.83, respectively; P less than 0.001 for both), but poorly correlated with urinary Ca (r = 0.21; P = NS and r = 0.42; P = 0.01, respectively), suggesting that these markers reflect different events of bone resorption. Similarly, after bisphosphonate therapy, urinary Pyr and D-Pyr levels fell by 31% and 50%, respectively, compared to 38% for hydroxyproline and 76% for urinary Ca. There was a significant correlation between posttreatment D-Pyr and serum Ca levels (r = 0.43; P less than 0.05). In summary, we found that the urinary excretion of Pyr and D-Pyr was markedly increased in hypercalcemic cancer patients and was adequately lowered by bisphosphonate therapy. The urinary excretion of the pyridinium cross-links, especially D-Pyr, should be helpful to specifically quantitate bone matrix resorption and monitor the inhibition of bone resorption in cancer patients receiving antiosteolytic drugs. PMID- 1740479 TI - Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women. AB - To investigate whether bone resorption exhibits a diurnal variation in healthy premenopausal women, we measured urinary excretion of pyridinoline and deoxypyridinoline cross-links (U-Pyr/Cr and U-D-Pyr/Cr) every 3 h over a 24-h period in 12 healthy premenopausal women (mean +/- 1 SD age, 32 +/- 5 yr). To study diurnal variation, U-Pyr/Cr and U-D-Pyr/Cr are the best available markers of bone resorption for a diurnal variation study, as they are not influenced by diet. Plasma osteocalcin and serum alkaline phosphatase (markers of bone formation) were also measured. A marked diurnal rhythm was observed in U-Pyr/Cr and U-D-Pyr/Cr, with the peak between 0500-0800 h and the nadir between 1400-2300 h. The fluctuation was 2-fold over the 24-h period, with a mean fall of 25-35% between 0800-1100 h. This study demonstrates a marked diurnal variation in the new biochemical markers of bone resorption, U-Pyr/Cr and U-D-Pyr/Cr, in premenopausal women. Furthermore, this study emphasizes the importance of regulating the time of the urine sample taken for measuring urinary pyridinium cross-links for clinical investigations as well as in clinical practice. PMID- 1740480 TI - Urinary hydroxypyridinium cross-links of collagen in primary hyperparathyroidism. AB - Urinary concentrations of the collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were determined in 87 patients with untreated or surgically treated primary hyperparathyroidism (PHPT). Eighty-four healthy individuals, matched for age and sex, constituted the control group for the excretion of pyridinium cross-links. In addition, a subgroup of 25 patients with PHPT was followed longitudinally for up to 2 yr after successful parathyroidectomy. Mean urinary excretion of PYD (46.8 +/- 2.7 nmol/mmol creatinine) and DPD (17.6 +/- 1.3 nmol/mmol creatinine) was significantly higher in patients with untreated PHPT than in normal subjects (P less than 0.001). In the group undergoing successful parathyroidectomy, mean urinary concentrations of PYD (34 +/- 2.5) and DPD (9.4 +/- 0.8) were similar to those in normal controls and significantly lower than those in the untreated patient population (P less than 0.001). The urinary concentration of both cross-links was significantly correlated with serum levels of both alkaline phosphatase and PTH. Mean urinary concentrations of both cross-link compounds decreased significantly within 6 months in patients followed longitudinally and as early as 2 weeks after surgery in individual patients compared to presurgical baseline values. These changes preceded the reduction in serum alkaline phosphatase and hydroxyproline by approximately 6 months. The results demonstrate that urinary hydroxypyridinium cross-links of collagen are useful indices in the clinical assessment of bone involvement in PHPT. PMID- 1740481 TI - Abnormalities in circadian patterns of bone resorption and renal calcium conservation in type I osteoporosis. AB - We compared changes over 24 h in 15 postmenopausal normal women (mean [+/- SD] age, 64 +/- 7 yr) with those in 15 postmenopausal women with type I osteoporosis and vertebral fractures (mean age, 64 +/- 5 yr). The serum osteocalcin concentration, a sensitive index of bone formation, increased by about 5% at night in both groups. Urinary deoxypyridinoline excretion, a sensitive index of bone resorption, increased by 48% at night (P less than 0.01) in the normal women, whereas in the osteoporotic women it was 62% higher overall (P less than 0.05), and the increase persisted into the morning. At night, urinary fractional excretion of calcium decreased by 20% (P less than 0.001) in the normal women, but was unchanged in the osteoporotic women; this circadian pattern differed between groups (P less than 0.05). The serum ionized calcium concentration did not change at night in either group. There was a trend (P = 0.07) for blunting of the nocturnal increase in the serum intact PTH level in osteoporotic women. Thus, the nocturnal serum ionized calcium level is maintained by decreased urinary calcium excretion and increased bone resorption in postmenopausal normal women, but almost entirely by increased resorption in postmenopausal osteoporotic women. This greater dependence on bone resorption during the nocturnal fast may account in part for the greater bone loss in osteoporotic women. PMID- 1740482 TI - Understanding the genetics of autoimmune thyroid disease--still an illusive goal! PMID- 1740483 TI - Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within families. AB - Clinical and epidemiologic observations, including the association of Graves' disease (GD) and Hashimoto's thyroiditis (HT) with the HLA gene complex, support a role for specific disease-related genes in the development of autoimmune thyroid disease (AITD). The combination of HLA and immunoglobulin heavy chain allotypes (Gm) has previously been reported to be predictive of AITD in multiply affected Japanese families. We have investigated the immunogenetics of AITD in families in the United States. Twenty-seven pedigrees including 15 with GD, 8 with HT, and 4 with both HT and GD were immunogenetically typed and analyzed for population and within family disease associations. The majority of families (63%) were multiplex for AITD. HLA-DR3 was increased in affected family members with GD and HLA-DR5 was increased in affected family members with HT. Formal linkage analysis was applied to test for coinheritance of disease with the HLA locus within families. The LIPED computer program was used to calculate the probability of linkage in terms of the lod score. Evidence from linkage analysis was consistently against linkage of either GD or HT to the HLA region under various penetrances and different modes of inheritance. The combination of HLA and Gm was not found to be predictive of disease in 7 selected multiplex families with multigenerational instances of AITD. T cell function was also examined in 3 pairs of siblings genetically identical for HLA and Gm but discordant for disease expression. We found no evidence of a global T cell defect in the small number of patients examined. We conclude that whereas there is an association of AITD with the HLA region, our linkage analysis demonstrates that alleles of the HLA region are not cosegregating with either GD or HT within these families. Thus, whereas HLA may increase susceptibility to AITD, as shown by the existence of an HLA association, the major genetic influence on the inheritance of AITD must be at another locus. PMID- 1740484 TI - Analysis of the preproPTH gene by denaturing gradient gel electrophoresis in familial isolated hypoparathyroidism. AB - Familial isolated hypoparathyroidism (FIH) is an inherited metabolic disorder characterized by hypocalcemia and hyperphosphatemia due to deficient secretion of biologically active PTH. We used denaturing gradient gel electrophoresis to screen for mutations in exon 1 and the coding region of the preproPTH gene. Exons 1, 2, and 3 of the preproPTH gene and flanking intronic regions were amplified by polymerase chain reaction using primers that were designed employing the MELT-MAP program. One oligonucleotide from each primer pair was synthesized with a 5'-GC clamp. Screening of amplified DNA from normal subjects and patients with FIH revealed two single base changes that altered migration of amplified preproPTH gene fragments through denaturing gels: 1) an A----G transition in intron 1; 10 nucleotides upstream of exon 2; and 2) a C----A transversion in exon 3 that conserves the arginine residue at codon 52 (CGA----AGA). By contrast, we did not detect pathogenic mutations in amplified regions of the preproPTH genes of 18 affected members of 5 FIH kindreds. The two polymorphisms occur frequently, and were therefore used to perform linkage analysis in 5 multiplex FIH families. Linkage analysis was inconclusive in 2 families and showed discordance between hypoparathyroidism and any of the preproPTH gene alleles in 2 other families. In another family, analysis was suggestive of linkage between hypoparathyroidism and inheritance of a specific preproPTH gene allele. These results indicate that denaturing gradient gel electrophoresis can be used to identify mutations in defined regions of the preproPTH gene, and to examine linkage of specific preproPTH alleles and inherited disorders of mineral metabolism. PMID- 1740485 TI - Hypothalamo-hypophyseal thyroid and gonadal function before and after erythropoietin therapy in dialysis patients. AB - We examined the effects of administration of two hypothalamic neurohormones, TRH and GnRH, for 3 days in five anemic male dialysis patients and five age-matched normal male volunteers. Patients on chronic hemodialysis have abnormal hypothalamo-hypophyseal thyroid and gonadal functions, including blunted TSH response to TRH, hyperprolactinemia, elevated basal levels of LH with exaggerated response to GnRH, and depressed FSH secretory response to GnRH. After correction of anemia with exogenous erythropoietin, these dialysis patients were given a single injection of the same hypothalamic hormones. The repeat studies after the correction of anemia showed normalization of 1) the TSH response to TRH, 2) basal GH and PRL levels, and 3) the FSH response to GnRH. Although these patients appear to have biochemical evidence of testicular failure, the gonadotropin response (FSH) to GnRH was not exaggerated. In addition, there was no increase in total T4 and free T4 after TRH administration. Although a free T3 response to TRH was present, it was remarkably blunted compared to that of controls. At the present time, it is not known whether these hormonal responses after the correction of anemia are due to better oxygenation or a trophic action of the erythropoietin. PMID- 1740486 TI - The modulation of circulating parathyroid hormone immunoheterogeneity in man by ionized calcium concentration. AB - Twenty normal individuals received 2-h iv infusions of CaCl2 and Na2 ethylenediamine tetra-acetate, with sampling every 15 min. PTH was measured by means of an intact hormone assay (I) and two carboxylterminal assays structured to react mostly with mid (M) or late (L) carboxylterminal fragments. A mathematical model was used to fit the sigmoidal relationship between ionized calcium (CA++) and PTH values. The influence of Ca++ on circulating PTH immunoheterogeneity was assessed via changes in L/I, M/I, and M/L ratios. Results are reported as means +/- SD. Response to hypocalcemia was highest with M (57.8 +/- 26.4 pmol/L, P less than 0.005 vs. L or I) and higher with L (20.1 +/- 5.6 pmol/L; P less than 0.0005 vs. I) than with I (14.1 +/- 6.4 pmol/L). L/I, M/I, and M/L decreased from 2.43 +/- 0.56 to 1.54 +/- 0.19 (P less than 0.0005), 8.44 +/- 2.38 to 4.36 +/- 4.07 (P less than 0.0005), and 3.49 +/- 0.71 to 2.86 +/- 0.76 (P less than 0.005), respectively, during Na2 ethylenediamine tetra-acetate infusion. Nonsuppressible PTH was again higher with M (13.7 +/- 4.8 pmol/L; P less than 0.0005 vs. L or I) and higher with L (2.8 +/- 0.7 pmol/L, P less than 0.0005 vs. I) than with I (0.5 +/- 0.3 pmol/L). L/I, M/I, and M/L ratios increased from 2.47 +/- 0.97 to 5.35 +/- 2.09 (P less than 0.0005), 8.90 +/- 3.10 to 29.56 +/- 14.89 (P less than 0.0005), and 3.62 +/- 0.90 to 5.30 +/- 1.91 (P less than 0.005) during CaCl2 infusion. The set-point for PTH stimulation by calcium was similar for M (1.15 +/- 0.035 mmol/L) and L (1.175 +/- 0.041 mmol/L) but significantly higher with the I assay (1.184 +/- 0.31 mmol/L; P less than 0.0005 vs. M). The M/I, L/I, and M/L ratio set-points were similar at 1.28 +/- 0.01, 1.27 +/- 0.01, and 1.29 +/- 0.02 mmol/L. Thus, even if proportionately more intact PTH and less carboxylterminal fragments are produced and secreted during hypocalcemia, the latter still predominate in the circulation. Furthermore, at high calcium values, secretion of fragments is less well inhibited than that of intact hormone. The lower secretion and higher ratio set-points suggest that the secretion and intracellular degradation of PTH have different sensitivities to inhibition by calcium. PMID- 1740487 TI - Identification of a 27-kilodalton protein with the properties of type I iodothyronine 5'-deiodinase in human thyroid gland. AB - N-Bromoacetyl-[125I]T4(BrAc[125I]T4) was used as affinity label to identify type I 5'-deiodinase (5'-D) in human thyroid glands. Affinity labeled proteins were analyzed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human thyroid microsomes labeled with BrAc[125I]T4 showed the most prominent radiolabeled band of protein at a mol wt of approximately 27,000 (p27). BrAc[125I]T4 incorporations into p27 were significantly higher in both Graves' and follicular adenomas than in normal thyroids. On the other hand, four cases out of five carcinomas were lower than the least value of normal thyroids. Furthermore, an excellent correlation was observed between 5'-D activities and quantities of p27 in all cases (r = 0.96; P less than 0.001). Labeling of p27 was strongly inhibited by preferred type I 5'-D substrate rT3, but to a lesser extent by poor substrate T4 or T3, and the type I 5'-D inhibitor, propylthiouracil and iopanoic acid, also inhibited the p27 labeling in normal and various diseases. In addition, the rate of enzyme inactivation by BrAcT4 equaled the rate of p27 labeling. These data suggest that p27 may be a type I 5'-D itself or at These data suggest that p27 may be a type I 5'-D itself or at least the substrate binding subunit of this enzyme in human thyroid, and that both Graves' and follicular adenoma thyroids contain larger amounts of it, and papillary adenocarcinoma thyroids smaller than normal amounts. PMID- 1740488 TI - Insulin-like growth factor-I (IGF-I) may not be essential for ovarian follicular development: evidence from IGF-I deficiency. AB - Insulin-like growth factor-I (IGF-I) stimulates growth and differentiation in follicular granulosa cells (GC). To examine whether this effect is prerequisite to human folliculogenesis, a patient with Laron-type dwarfism (IGF-I deficiency secondary to GH receptor abnormality) was examined while undergoing in vitro fertilization treatment. Despite low levels of IGF-I in serum and follicular fluid (less than 3 and less than 2 nmol/L) and very high levels of IGF-I-binding protein, the patient developed normal ovarian follicles. After the administration of GnRH analog (GnRHa) and human menopausal gonadotropin in a dose similar to that used in normovulatory women, estradiol (E2) levels reached above 5000 pmol/L on the day of hCG administration, and mature fertilizable oocytes were retrieved during ovum pickup. The patient's GC E2 production, tested in a primary culture, did not respond to IGF-I after 4 days of incubation, while control cultures showed a significant increase. Only after a priming period of 7 days did IGF-I have a significant effect on E2 production, as observed in the patient's GC culture. This delayed response suggests that the patient's GC were not exposed in vivo to IGF-I. Our data support the view that IGF-I is not required for normal follicular development, but is, rather, a nonessential modulator of FSH action. PMID- 1740489 TI - Salt-wasting congenital adrenal hyperplasia: detection and characterization of mutations in the steroid 21-hydroxylase gene, CYP21, using the polymerase chain reaction. AB - We have characterized mutations in the steroid 21-hydroxylase gene (CYP21) in salt-wasting congenital adrenal hyperplasia (SW-CAH) subjects, healthy control subjects, and affected sibling pairs with SW-CAH. To identify point mutations in CYP21, we have used an improved polymerase chain reaction methodology that allows analysis of the entire CYP21 gene. In addition, we have used polymerase chain reaction to search for abnormally spliced mRNAs resulting from putatively abnormal CYP21 genes transfected into COS1 cells. We found that all 26 SW-CAH subjects from whom DNA could be completely analyzed, had mutations that could account for the 21-hydroxylase enzyme deficiency. These mutations included CYP21 gene deletion, conversion to the inactive CYP21P form, point mutations leading to amino acid substitutions or stop codons, small gene deletions, and a point mutation in intron-2 that leads to an abnormally spliced mRNA. The point mutation in intron-2 was directly shown to activate a cryptic splice site 19 basepairs from exon-3 of CYP21 and thereby cause a reading frame mutation. This CYP21 mutation was frequently found in our white SW-CAH subjects, while the frequency of this mutation was extremely low in a racially matched control population. Furthermore, affected sibling pairs shared this mutation in all cases examined. The results presented should have important applications for the prenatal diagnosis of CAH. PMID- 1740490 TI - Robustness of the male lactotropic axis to the hyperprolactinemic stimulus of primary thyroidal failure. AB - Primary hypothyroidism is a presumptive proximate basis for increased serum PRL concentrations. However, most studies to date have been performed in females and do not address the possible effect of sex differences. In the present study we investigated the 24-h patterns of pulsatile PRL release in 10 hypothyroid men (24 h mean +/- SEM: total T4, 35 +/- 8 nmol/L; TSH, 55 +/- 10 mU/L) by sampling blood at 10-min intervals for 24 h. The study was repeated in 5 men, 5-7 months and again 14-36 months after treatment with levothyroxine. The control group consisted of 7 normal age-matched euthyroid men. The mean 24-h serum PRL concentration of 4.9 +/- 0.6 micrograms/L in 10 hypothyroid men was not significantly different from the value of 4.9 +/- 0.5 micrograms/L found in the normal group (P greater than 0.5). Pulsatile features of PRL release were evaluated by Cluster analysis, which revealed normal mean PRL peak frequency (12.6 +/- 0.7 vs 13.4 +/- 0.6 pulses/24 h; P greater than 0.5), maximal peak amplitude (6.1 +/- 0.7 vs. 6.7 +/- 0.6 micrograms/L; P greater than 0.5), peak increment (2.2 +/- 0.3 vs. 2.6 +/- 0.3 micrograms/L; P = 0.3), mean valley (4.2 +/- 0.6 vs. 4.4 +/- 0.4 micrograms/L; P greater than 0.5), and prepeak nadir (3.6 +/- 0.5 vs. 3.6 +/- 0.4 micrograms/L; P greater than 0.5) PRL concentrations. Five to 7 months of T4 therapy in 5 hypothyroid men caused significant decreases in the mean 24-h (2.9 +/- 0.5 vs. 6.1 +/- 1.2 micrograms/L; P less than 0.05), interpulse valley (2.5 +/- 0.4 vs. 5.2 +/- 1.1 micrograms/L; P less than 0.05), and prepeak nadir (2.3 +/- 0.3 vs. 4.6 +/- 1.0 micrograms/L; P less than 0.05) PRL concentrations. These values returned to normal after 14-36 months of treatment. Cosinor analysis revealed preserved circadian PRL rhythmicity during hypothyroidism, with a normal circadian mesor (mean), amplitude, and acrophase. In summary, we have demonstrated normal mean 24-h serum PRL concentrations as well as normal pulsatile and circadian patterns of PRL release in men with primary hypothyroidism. These results stand in contrast to previous reports of increased serum PRL concentrations observed predominantly in hypothyroid premenopausal women. The foregoing disparity suggests the possibility of a role for estrogen in enhancing the effect of hypothyroidism on PRL release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1740491 TI - Evidence for a critical role of progesterone in the regulation of the midcycle gonadotropin surge and ovulation. AB - Serum concentrations of progesterone begin to rise just before the midcycle gonadotropin surge that leads to ovulation. To examine the role of progesterone in the regulation of these events, we evaluated the effects of a low dose (1 mg/day, orally) of the antiprogesterone RU 486 on the timing of the gonadotropin surge and ovulation in normally cycling women. The drug or a placebo was given for 5 or 15 days, starting when the dominant follicle reached 14-16 mm. RU 486 consistently delayed the timing of the midcycle gonadotropin surge and the subsequent collapse of the dominant follicle, despite rising estradiol concentrations and normal follicular development. Unexpectedly, RU 486 also delayed the emergence of the periovulatory progesterone rise. The addition of progesterone (5-10 mg/day, im, for 2 days) to a 5-day course of RU 486 after the emergence of a mature follicle readily induced LH and FSH surges and completely reversed the effects of RU 486 at midcycle. Our results suggest that RU 486 delays the midcycle gonadotropin surge and ovulation by suppressing or antagonizing an ovarian progestational signal. Progesterone may, thus, represent the ultimate ovarian signal to the estrogen-primed hypothalamic-pituitary unit to trigger the gonadotropin surge that leads to ovulation. PMID- 1740492 TI - Defective ring A reduction of cortisol as the major metabolic error in the syndrome of apparent mineralocorticoid excess. AB - Impaired peripheral metabolism of cortisol in the syndrome of apparent mineralocorticoid excess is currently understood to be causally related to the severe but otherwise unexplained manifestations of mineralocorticoid excess. A normally ambivalent mineralocorticoid receptor responding equally well to glucocorticoids and mineralocorticoids requires prereceptor inactivation of glucocorticoids to elicit a specific mineralocorticoid effect. The failed inactivation step in the form of the syndrome of apparent mineralocorticoid excess first described (type 1) involves the 11 beta-hydroxydehydrogenation of cortisol to cortisone. In another form of the syndrome (type 2) this conversion occurs normally in the face of otherwise similar clinical and biochemical features. Markedly decreased cortisol metabolic clearance in the type 2 form suggested impairment of a major component of that clearance, ring A reduction. A noninvasive method was developed for measuring the conversion of cortisol to tetrahydrocortisol and allotetrahydrocortisol, and this step was found to be profoundly decreased in both type 1 and type 2 forms. Thus, the major abnormality in the peripheral metabolism of cortisol common to both forms involved ring A reduction, not 11 beta-hydroxydehydrogenation. Since ring A reduction was better correlated with the manifestation of mineralocorticoid excess in both forms of the syndrome, this step might also be a normal major prereceptor mechanism conferring mineralocorticoid specificity. PMID- 1740493 TI - Hypothalamic gonadotropin-releasing hormone secretion and follicle-stimulating hormone dynamics during the luteal-follicular transition. AB - To define the precise neuroendocrine characteristics of the luteal-follicular transition, 11 normal women underwent 12 frequent sampling studies at 10-min intervals for 48 h at various points during the transition from one cycle to the next. Daily blood samples captured both the preceding and subsequent LH surges, so that studies could be characterized in relation to the preceding LH peak (LH+), the subsequent LH peak (LH-), and menses (M). In the frequent sampling study, LH and FSH were measured in all samples, and estradiol (E2) and progesterone (P) were measured in 2-h pools. The frequency of pulsatile LH secretion increased 4.5-fold over an 8-day period spanning the luteal-follicular transition. This increase in LH pulse frequency was strongly related to the preceding LH peak (r = 0.82; P less than 0.00001), but was not at all related to the onset of menses. When the temporal markers (i.e. LH+, LH-, and M) were removed from the analysis, LH pulse frequency was inversely related to the log of serum P (r = 0.50; P less than 0.005), but not E2. FSH levels increased both within the individual studies (P less than 0.005) and in the group as a whole over the duration of the luteal-follicular transition. Mean FSH rose 3.5-fold compared to less than a 2-fold increase in mean LH. As with LH pulse frequency, the increase in FSH was most strongly related to the preceding LH peak, but was also significantly associated with the subsequent LH peak and the onset of menses. The relationship between FSH and the number of days from the preceding LH peak is even better fit by a second degree polynomial, which revealed an abrupt increase in LH beginning at LH+11. With the temporal markers excluded, the increase in FSH related only to LH pulse frequency (r = 0.62; P less than 0.001). FSH was not statistically related to the decreases in P or E2, which are also key variables at this stage of the menstrual cycle. We reached the following conclusions. 1) A dramatic increase in LH pulse frequency, and by inference GnRH pulse frequency, accompanies the selective rise in FSH levels during the luteal follicular transition of the normal menstrual cycle. 2) Both the increase in GnRH pulse frequency and the rise in FSH levels during this transition are strongly related to the preceding LH peak, while the clinical marker of menses is a relatively poor indicator of these events.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1740494 TI - Cortisol resistance in acquired immunodeficiency syndrome. AB - This study concerns 9 iv drug abusers with acquired immunodeficiency syndrome (AIDS) who developed hypercortisolism without the clinical signs or metabolic consequences of hypercortisolism. All patients were characterized by an Addisonian picture (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis). An acquired form of peripheral resistance to glucocorticoids was suspected. We, therefore, examined glucocorticoid receptor characteristics on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which is one of the effects of glucocorticoid receptor activation. Glucocorticoid receptor density was increased in AIDS patients with an Addisonian picture (group 1; 16.2 +/- 9.4 fmol/million cells) compared to values in 12 AIDS patients without an Addisonian picture (group 2; 6.05 +/- 2.6 fmol/million cells; P less than 0.01) and sex- and age-matched controls (3.15 +/- 2.3 fmol/million cells; P less than 0.01). The affinity of glucocorticoid receptors (Kd) was strikingly decreased (9.36 +/- 3.44 nM in group 1; 3.2 +/- 1.5 nM in group 2; 2.0 +/- 0.8 nM in controls; P less than 0.01). [3H]Thymidine incorporation was decreased dose dependently by dexamethasone in controls and patients; the effect was significantly blunted (P less than 0.05) in group 1 patients, which suggests that activation of glucocorticoid receptor is impaired as a result of the glucocorticoid receptor abnormality. In conclusion, AIDS patients with hypercortisolism and clinical features of peripheral resistance to glucocorticoids are characterized by abnormal glucocorticoid receptors on lymphocytes. Resistance to glucocorticoids implies a complex change in immune endocrine function, which may be important in the course of immunodeficiency syndrome. PMID- 1740495 TI - Function of DR-positive thyrocytes from patients with Graves' disease: quantitative analysis of thyroid peroxidase content by fluorescent photometry. AB - A considerable number of thyrocytes in patients with autoimmune thyroiditis ectopically express HLA-DR antigen. Furthermore, it has been reported that interferon-gamma-induced DR-positive thyrocytes in vitro secrete less thyroid hormone in response to TSH stimulation compared with DR-negative ones. However, the function of the intrinsically DR-positive thyrocytes is unknown. To evaluate their function, we stained by immunofluorescence for both DR antigen and thyroid peroxidase (TPO) in thyroid epithelial cells from patients with Graves' disease. We also measured the quantity of DR antigen and TPO using fluorescent photometry. The content of TPO was not significantly reduced in DR-positive thyrocytes compared with that in DR-negative thyrocytes. The TPO content is one measure of thyrocyte function. There was no significant difference between DR-positive and DR-negative thyrocytes. In conclusion, the function of DR-positive thyrocytes in vivo was not suppressed compared with that of DR-negative thyrocytes. PMID- 1740496 TI - Low urinary growth hormone values in patients with Turner's syndrome. AB - Short stature is one of the major symptoms in Turner's syndrome (TS). The cause of short stature is not clearly known at present. In this study we initially assessed GH secretory status in TS by determinations of urinary human (h) GH excretion for 2 consecutive days. Secondly, the therapeutic dose of hGH used for treatment of short stature in TS was evaluated by measurements of urinary hGH after recombinant hGH (r-hGH) injections. Twenty-four-hour urinary hGH excretion for the 2 days combined was significantly lower in patients with TS than in normal children [2.3 +/- 1.8 ng/day (n = 7) vs. 13.4 +/- 3.2 (n = 16); P less than 0.001], although four of seven patients with TS had normal GH responses to the provocative tests. The mean level of urinary hGH in TS after 2 days was comparable to that in complete GH deficiency (1.9 +/- 0.9 ng/day; n = 14) that we previously reported. Treatment with daily sc injections of 1.0 IU (0.37 mg)/kg.week r-hGH, given in seven divided doses, normalized urinary hGH excretion and induced remarkable catch-up growth in all patients with TS. These results indicate that the 24-h endogenous GH secretion in seven patients with TS is impaired. The measurement of 24-h urinary hGH excretion may prove to be useful as a marker to assess the abnormal GH secretion and the adequacy of treatment with hGH in patients with TS. The therapeutic dose of hGH in TS is approximately 0.37 mg/kg.week, given in seven divided doses. To convert international units of r-hGH to milligrams, divide by 2.7. PMID- 1740497 TI - Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. AB - None of the current or experimental androgen treatment modalities for male hypogonadism has been reported to produce physiological concentrations or circadian variations in testosterone (T) and its metabolites, dihydrotestosterone (DHT) and estradiol (E2). This investigation describes a novel transdermal dosage form designed to enhance the delivery of native T across nonscrotal skin. The main objective was to determine whether the nightly application of two experimental transdermal patches to different sites on the body (e.g. back, chest, arms, etc.) would result in normal plasma levels of T, DHT, and E2 for men and mimic the normal circadian variation. Six hypogonadal males (aged 24-66 yr) were studied 4 weeks after stopping T ester treatment. After single application of two patches, T levels increased from a pretreatment baseline of 5.8 +/- 0.94 nmol/L (mean +/- SE; 167 +/- 27 ng/dL) to an average peak concentration of 44.1 +/- 4.8 nmol/L (1273 +/- 138 ng/dL) 5.7 +/- 0.6 h after application and reached a 24-h level of 16.9 +/- 2.9 nmol/L (488 +/- 85 ng/dL). DHT and E2 levels exhibited parallel variations within the normal reference ranges. During 4 weeks of daily evening application to various sites on the torso, the mean delivery of T from two patches was 5.2 +/- 0.1 mg/day (approximately 20% of the patch content), and morning T levels were within the normal limits. On day 28 of treatment, the 24-h plasma profiles of T, DHT, and E2 (obtained with two patches on the back) approximately mimicked the normal circadian variations reported in healthy young men. The time-averaged T level was 21.8 +/- 2.9 nmol/L (629 +/- 84 ng/dL), and the plasma concentration ratios of DHT/T (0.07 +/- 0.01) and E2/T (0.005 +/- 0.001) were within the normal range. SHBG concentrations were not significantly altered over the 4 weeks of treatment. The patches were well tolerated, except for one patient who developed a local reaction to an excipient during the third week of treatment. Two of the patients (one with Klinefelter's syndrome) completed several months of continuous therapy. T, DHT, and E2 have remained in the range of normal, and plasma LH levels in the patient with Klinefelter's syndrome became normal. Subjective improvement in symptoms has continued, and tolerability has been good in both patients. These results indicate that the enhanced transdermal delivery of T across nonscrotal skin is a patient-friendly androgen replacement modality and produces physiological concentrations of T and its metabolites, which are unattainable with other treatment modalities. PMID- 1740498 TI - Induction and superinduction of messenger ribonucleic acid specific for aromatase cytochrome P-450 in cultured human skin fibroblasts. AB - Aromatase cytochrome P-450 (cytochrome P-450AROM) catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. Several studies indicate that cytochrome P-450AROM activity is induced by glucocorticoids such as dexamethasone (DEX) and superinduced by DEX plus cycloheximide (CHX). We have used cultured human skin fibroblasts as a model system to investigate the regulation of aromatase gene expression. Whereas Northern blot analysis of total cellular RNA or poly (A)+ RNA from untreated strains of normal human skin fibroblasts failed to demonstrate any hybridization with a specific human placental cytochrome P-450AROM complementary DNA, analysis of RNA from cells treated with DEX demonstrated hybridization of the cytochrome P-450AROM complementary DNA to two transcripts of about 2.5 and 3.0 kilobases. Incubation of cells with DEX plus CHX resulted in a further increase in levels of cytochrome P-450AROM messenger RNA (mRNA) when compared to cells treated with DEX alone, suggesting that inhibition of protein synthesis superinduces transcription of the cytochrome P-450AROM gene. By contrast, levels of beta-actin mRNA were not affected by treatment with DEX and CHX. Treatment of cells with CHX alone did not produce a change in either aromatase activity or levels of cytochrome P-450AROM mRNA transcripts. These results indicate that aromatase activity is regulated by changes in the concentration of cytochrome P-450AROM mRNA, and imply that control of cytochrome P-450AROM gene expression is at the level of gene transcription. We conclude that the cytochrome P-450AROM gene is regulated by a complex mechanism that includes both positive and negative transcription factors. PMID- 1740499 TI - Effect of glycemic control on the overnight dexamethasone suppression test in patients with diabetes mellitus. AB - Because many of the clinical features associated with Cushing's syndrome are frequently found in patients with diabetes mellitus, diabetic patients are often evaluated for Cushing's syndrome. The initial test for Cushing's syndrome is the 1 mg overnight dexamethasone suppression test (DST), but its value as a screening test in diabetic subjects, especially those with poor glycemic control, has been questioned. To address this issue, an overnight DST was administered to 100 subjects with diabetes. Only 7 patients failed to suppress their plasma cortisol to less than 140 nmol/L (5.0 micrograms/dL), achieving a specificity of 93%. There was no relation between acute glycemic control (as measured by the mean of 4 serum glucose values obtained before receiving dexamethasone) or chronic glycemic control (as measured by glycohemoglobin) and false positive responses to the 1 mg overnight DST. The mean of the measures of acute glycemic control of the 7 subjects who had false positive results, 14.4 +/- 2.8 mmol/L, was not significantly different than that of the 93 subjects with normal responses, 13.2 +/- 3.3 mmol/L. Similarly, the mean glycohemoglobin of the subjects with false positive results, 12.8 +/- 2.4%, was not significantly different than that of the subjects with normal responses, 12.9 +/- 2.5%. There was no correlation between plasma cortisol after dexamethasone and glycohemoglobin (r = 0.05), and only a weak correlation with the mean serum glucose (r = 0.21). We conclude that the 1 mg overnight DST is a valid screening test for Cushing's syndrome in patients with diabetes, regardless of glycemic control. PMID- 1740500 TI - A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction. AB - Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD. PMID- 1740501 TI - Hypothalamo-pituitary axis by magnetic resonance imaging in isolated growth hormone deficiency patients born by normal delivery. AB - Magnetic resonance imaging was performed using a 1.5 Tesla magnet in 22 children (14 boys and 8 girls) between 5-20 yr of age with isolated GH deficiency (IGHD), born by normal vaginal delivery without any birth asphyxia or trauma. A total of 22 children (10 boys and 12 girls) without short stature and endocrine disease were evaluated as controls. The IGHD group had a height velocity less than 4 cm/yr and delayed bone age. The peak GH levels were less than 10 micrograms/L (mean, 2.4 micrograms/L). The height of the pituitary gland ranged from 3-7.5 mm in controls. An intact stalk was observed in 21 children with IGHD, with nonvisualization in 1. An apparently thin stalk was seen in 6. The posterior lobe identified by the hyperintensity signal, had a mean diameter of 1.84 mm and was located in a normal position in 21 children. An ectopic posterior pituitary hyperintensity was present in 1 patient. The anterior pituitary was hypoplastic in 17 children, with partial empty sella in 13. A total of 5 children had associated brain anomalies, such as Arnold Chiari malformation, craniovertebral malformation with basilar impression, degenerative plaques around posterior horn of lateral ventricle and parietal area, and infarcts in caudate nucleus and putamen. These findings suggest that IGHD was not related to transection or compression of the stalk. PMID- 1740502 TI - Evidence for increased liver glycogen in patients with noninsulin-dependent diabetes mellitus after a 3-day fast. AB - In order to assess hepatic glycogen stores in patients with noninsulin dependent diabetes mellitus (NIDDM) after a 3-day fast, the incremental glucose response to 1.0 mg iv glucagon (glucose area under the curve, glucoseAUC) was assessed in 19 obese diabetic subjects after an overnight (14 h) fast and again after a 3-day (64 h) fast. Results were compared to those of lean (n = 6) and obese (n = 15) nondiabetic subjects. During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. However, in contrast to the fall in glucoseAUC observed in the lean (92.4 +/- 15.4 to 39.9 +/ 8.1 mmol min-1 L-1, P less than 0.02) and obese (64.4 +/- 11.1 to 48.4 +/- 9.4 mmol min-1 L-1) subjects, the glucoseAUC increased in diabetic subjects from 81.6 +/- 8.6 to 103.9 +/- 8.8 mmol min-1 L-1 during the fast, and was significantly greater than that of either the lean (P less than 0.001) or obese (P less than 0.001) nondiabetic subjects after the 64-h fast. Evidence that the glucose response to glucagon after a 64-h fast represents glycogenolysis and not gluconeogenesis was provided by studies in 10 additional subjects (5 obese nondiabetic subjects and 5 patients with NIDDM). Overall hepatic glucose output calculated from glucose kinetic data [( 3-3H]glucose) increased in diabetic and nondiabetic subjects during the first 30 min after glucagon administration and fell progressively thereafter. However, no increase in alanine gluconeogenesis (14C-alanine incorporation into glucose) was observed after glucagon administration in either subject group. The paradoxical accumulation of glycogen in the patients with NIDDM during the fast occurred despite basal rates of hepatic glucose output on the third day of the fast which were greater than those of obese nondiabetic subjects (9.0 +/- 1.2 vs. 5.6 +/- 0.5 mumol kg-1 min-1, P less than 0.05). A glycogen sparing action of increased gluconeogenesis is proposed as the explanation for the preservation of liver glycogen in patients with NIDDM. PMID- 1740503 TI - Compound heterozygous mutations (Arg 239----stop, Pro 342----Thr) in the CYP17 (P45017 alpha) gene lead to ambiguous external genitalia in a male patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency. AB - 17 alpha-Hydroxylase deficiency is characterized by defects in either or both the 17 alpha-hydroxylase/17,20-lyase activities. We have, for the first time, elucidated the molecular basis of the deficiency in a male pseudohermaphrodite with ambiguous external genitalia resulting from partial combined deficiency of both activities. The patient is found to be a compound heterozygote, carrying two different inherited mutant alleles in the cytochrome P45017 alpha (CYP17) gene. One allele, from his mother, contains a stop codon (TGA) in place of arginine (CGA) at amino acid position 239 in exon 4. Because this occurs at the N-terminal side of the heme binding sequence, the putative resultant truncated protein is nonfunctional. The second allele, from his father, contains a missense mutation encoding the substitution of proline (CCA) by threonine (ACA) at position 342 in exon 6. Reconstruction of this mutation by site-directed mutagenesis into human P45017 alpha cDNA followed by expression in COS 1 cells leads to the same amount of immunodetectable P45017 alpha protein as found with expression of the normal P45017 alpha cDNA, although both the 17 alpha-hydroxylase and 17,20-lyase activities are found to be reduced to 40-45% of those of the normal enzyme. The presence of ambiguous external genitalia in this 46 XY individual indicates that greater than 20% of the total normal 17,20-lyase activity is required for complete virilization in the male. PMID- 1740504 TI - Mechanisms of hepatic and peripheral insulin resistance during acute infections in humans. AB - To examine mechanisms of insulin resistance, nine patients (age 33 +/- 4 yr, body mass index 22 +/- 1 kg/m2) with acute bacterial or viral infections and in six matched normal subjects were studied. Endogenous glucose appearance (Ra), glucose disappearance (Rd), and recycling, the percentage of plasma lactate originating from plasma glucose, total glucose oxidation, and whole body and forearm muscle Rd were measured after an overnight fast in the basal state and during physiological hyperinsulinemia (serum insulin approximately 215 pmol/L). Basally Ra, Rd, glucose recycling, and oxidation were similar in both groups. During hyperinsulinemia, insulin stimulated plasma Rd approximately 35% less (17.6 +/- 1.3 vs. 26.8 +/- 3.6 mumol/kg.min, P less than 0.01, patients vs. normal subjects), and inhibited endogenous Ra less in the patients (from 13.3 +/- 0.8 to 5.3 +/- 0.8 mumol/kg.min) than in the normal subjects (from 12.8 +/- 1.0 to 2.1 +/- 1.2 mumol/kg.min, P less than 0.01). The decrease in whole body Rd was largely explained by a approximately 75% reduction in muscle Rd (5.6 +/- 1.5 vs. 20.8 +/- 3.3 mumol/kg muscle.min, P less than 0.01, patients vs. normal subjects). The defect in Rd was confined to nonoxidative (4.8 +/- 1.1 vs. 11.0 +/ 3.0 mumol/kg.min, P less than 0.01, patients vs. normal subjects) but not to oxidative glucose metabolism. The percentage of plasma lactate derived from plasma glucose during hyperinsulinemia averaged 63 +/- 6% in the patients and 79 +/- 5% in the normal subjects, indicating that glycogenolysis did not excessively dilute glycolytic carbons in the patients. We conclude that during natural infections in humans, abnormal glucose metabolism is confined to the insulin stimulated state and involves a marked defect in muscle glucose uptake and glycogen synthesis, as well as a less marked hepatic defect. PMID- 1740505 TI - Evidence for the presence of differently glycosylated forms of prorenin in the plasma of anephric man. AB - Previously, we unexpectedly observed that plasma inactive renin (trypsin activatable renin) in bilaterally nephrectomized rats is not prorenin. To determine whether plasma inactive renin in anephric man is prorenin, we examined the immunological and biochemical properties of plasma inactive renin from five anephric patients. There were significant concentrations of inactive renin (5.33 +/- 2.08 ng/L.s) in plasma of anephric patients, while active renin was negligible (0.06 +/- 0.01 ng/L.s). The inactive renin from anephric patients could be immunoprecipitated 97 +/- 1% by specific antiserum against the prosegment portion of prorenin. Specific antimature renin serum completely inhibited the angiotensin-I-generating activity of inactive renin induced by trypsin treatment. The molecular mass of inactive renin from anephric patients (49.0 +/- 0 kDa), estimated by gel permeation high performance liquid chromatography, was similar to that of normal human plasma prorenin (48.2 +/- 0.8 kDa). These results indicate that plasma inactive renin in anephric man is prorenin, findings different from our previous observations obtained in anephric rats. Concanavalin-A chromatography separated inactive renin from anephric patients into three forms, including the column-unbound form, the loosely bound form, and the tightly bound form. Thus, in anephric man, differently glycosylated multiple forms of prorenin are released into the circulation from an extrarenal organ(s). PMID- 1740506 TI - Reduction in size of a thyrotropin- and gonadotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog). AB - TSH as well as alpha-subunit, secretion has been shown to decrease after the administration of the somatostatin analog octreotide acetate (SMS 201-995). We have studied a 59-yr-old, male patient with a TSH- and gonadotropin-secreting tumor who, because of severe cardiomyopathy, was treated with long-term somatostatin analog rather than surgical resection of the pituitary tumor. Thirteen weeks of treatment with thrice daily sc injection of 100 micrograms octreotide acetate resulted in decreased TSH and alpha-subunit secretion, normal serum thyroid hormone levels, reduction in LH and testosterone level, and significant tumor size reduction. Long-term treatment for 51 weeks has not been associated with any significant side effects. We have shown that octreotide acetate may be a therapeutically valuable modality for certain patients with neoplastic inappropriate secretion of TSH (NIST). A probable effect of octreotide acetate on neoplastic gonadotropes, as evidenced by the reduction of the LH level with a concomitant decrease in testosterone level, is, likewise, suggested. PMID- 1740507 TI - Utility of an oral diffusion sink (ODS) device for quantification of saliva corticosteroids in human subjects. AB - Measurement of cortisol by assay of single blood or saliva samples is inherently imprecise due to the episodic secretion of cortisol. In addition, assay of blood usually quantifies total cortisol, rather than separating free hormone, which is proportionately the much smaller fraction. Furthermore, the free fraction may be disproportionately higher in hypercortisolism. Urinary free cortisol is one measure that provides both a time integral and a focus on the free fraction, but it is inconvenient and prone to collection error in unsupervised ambulatory subjects. The Oral Diffusion Sink (ODS) apparatus takes up corticosteroids from saliva according to first-order kinetics and may provide a practical alternative. We assessed the utility of the ODS in a study of seven healthy volunteers admitted to the CRC for three days. Data on day two from 0700-1100 h and 1100 1500 h were compared between the ODS and three other means of assessing cortisol: urinary free cortisol (UFC), blood, and saliva. The subjects all tolerated wearing the ODS device without any complaint. High correlations were observed between ODS values vs. data for UFC, plasma, and saliva determinations. In summary, the ODS device was well tolerated and collected reliable corticosteroid data, and thus provides a new, non-invasive methodology for studies of HPA function in health and disease. PMID- 1740508 TI - Diagnosing fungal infections in immunocompromised hosts. PMID- 1740509 TI - Parenchymatous thyroid nodules: a histocytological study of 31 cases from a goitrous area. AB - AIMS: To analyse the benefits and limitations of fine needle aspiration in the cytological differentiation of parenchymatous nodular goitres from follicular tumours in an endemic area. METHODS: Cytological smears of fine needle aspirates from 31 parenchymatous nodular goitres were studied. A sample from the punctured nodules was fixed in formalin and stained with haematoxylin and eosin for histological analysis. RESULTS: All nodules occurred in a multinodular gland, were well circumscribed, did not compress surrounding thyroid tissue, and for the most part, were unencapsulated. Two cases showed cytological features of nodular goitre, two of colloid cysts; the remaining 27 were cytologically indistinguishable from follicular lesions. CONCLUSIONS: Most of the parenchymatous nodules studied had features suggestive of follicular lesions or neoplasia, but surgical treatment should only be considered after hormone treatment has proved unsuccessful, and when they are not suspected as malignant clinically. Fine needle aspiration is useful as a diagnostic and screening aid, but the results should be interpreted with caution to prevent unnecessary surgery. PMID- 1740510 TI - Association of Helicobacter pylori with HLA-DR antigen expression in gastritis. AB - AIMS: To assess the association between Helicobacter pylori-associated gastritis and HLA-DR antigen (class II antigen) expression. METHODS: Fifty endoscopic gastric biopsy specimens were studied for the presence of H pylori, degree and type of inflammation, and for HLA-DR antigen expression in the epithelium. The cases were chosen to represent different categories: inflamed gastric mucosa with (n = 13) and without (n = 20) H pylori, and non-inflamed mucosa (n = 17). RESULTS: The antigen was aberrantly expressed in the antral mucosal epithelium in 11 of 12 cases (92%) with acute-on-chronic gastritis when H pylori was also present. It was present in the antrum in only seven of 18 H pylori negative cases (39%) with acute-on-chronic/chronic gastritis. One of three cases of acute gastritis and three of seven cases of chronic gastric erosions (non-inflamed category) showed positive staining. Generally, there was more staining in the antral than body mucosa and in the surface/foveolar epithelium than in the glands. No aberrant HLA-DR antigen expression was found in the 10 cases of normal gastric mucosa examined. CONCLUSIONS: These findings suggest that H pylori may have a role in the induction of class II HLA antigen expression in chronic gastritis and lend support to the view that these organisms may be responsible for part of the inflammatory response. PMID- 1740511 TI - Salmonella bacteraemia in England and Wales, 1981-1990. AB - AIMS: To report the incidence of nontyphoidal salmonellas in England and Wales and identified in the Division of Enteric Pathogens, London between 1981 and 1990. METHODS: Strains were serotyped and phage typed for Salmonella typhimurium, S enteritidis, and S virchow, using established methods. RESULTS: Overall, less than 2% of nontyphoidal salmonellas isolated from humans were from blood culture. The highest numbers of bloodstream isolates were from infections caused by S enteritidis and S typhimurium, but the highest incidence of septicaemias was attributable to infections with S cholerae-suis, S dublin, and S virchow. 2.2% of S typhimurium isolates phage type 204C were from blood culture; likewise, 5.5% of S virchow phage type 19. This could be a cause for concern as most isolates of both these phage types are multiresistant to antimicrobial drugs. CONCLUSIONS: Salmonella septicaemia is rare in England and Wales in other than a few serotypes of limited epidemiological importance. PMID- 1740512 TI - Enzyme immunoassay for anti-treponemal IgG: screening or confirmatory test? AB - AIMS: To review the performance of the Venereal Diseases Research Laboratory (VDRL) test and the Treponema pallidum haemagglutination assay (TPHA) as a combined screen for syphilis to provide a baseline for assessing screening by anti-treponemal IGG EIA. METHODS: Between 1980 and 1987 all serum samples were screened by both VDRL and TPHA tests. The FTA-ABS test was also used in suspected early primary syphilis, or when one of the other tests was positive. A positive result in a screening test was confirmed by quantitative testing. From 1988 all specimens were screened with an enzyme immunoassay (Captia Syph G) as a single screening test. RESULTS: Of the 44 primary, 47 secondary, and 38 early latent cases of syphilis, the VDRL and TPHA detected 32 (73%) and 31 (71%) of the primary cases; the combination detected 37 (84%). All 85 cases of cases of secondary and early latent infection were reactive in the TPHA test, whereas the VDRL was reactive in only 68 (80%). EIA had a reported sensitivity of 82% for primary infection. CONCLUSIONS: EIA can be used as a single screening test for detecting early syphilis because its results are comparable with those of the combined VDRL and TPHA tests. The conventional VDRL test should not be used as a single screening test. PMID- 1740513 TI - Evaluation of enzyme linked immunosorbent assay for screening urinary tract infection in elderly people. AB - AIMS: To evaluate the Uristat test, an indirect enzyme linked immunosorbent assay for the qualitative detection of antibodies in urine, as a screening, and in the diagnosis of urinary tract infection in the elderly. METHODS: Semiquantitative culture was compared with conventional microscopy, dipstick analysis and the ELISA. In the ELISA, 371 urine samples were examined for antibodies to an antigen mixture of six common urinary pathogens. RESULTS: The sensitivity was 91% and the specificity 25% for the ELISA. The negative predictive value was 81% and the positive predictive value was 43%. CONCLUSIONS: In its present form the Uristat test has no clear advantages over conventional bacteriological techniques for screening urine samples for infection in an elderly population. PMID- 1740514 TI - Screening tests for pathogenic corynebacteria. AB - AIM: To provide simple tests that would help in the identification of corynebacteria that produce diphtheria toxin. METHODS: A collection of 99 freshly isolated corynebacteria was assembled and the cultures identified by conventional tests confirmed by an identification kit. Modifications were made to procedures for preparation of the culture medium for the Elek test and to the test for detection of pyrazinamidase (pyrazine carboxylamidase) activity. These two together with an indicator medium for cystinase activity were applied to the collection of organisms. RESULTS: Cystinase was detected in all 61 members of the toxigenic species and none produced pyrazinamidase. In contrast, all but two of the 38 representatives of non-toxigenic species yielded pyrazinamidase and none formed cystinase. Of the 61 cystinase producing cultures (which were also pyrazinamidase negative), 21 gave a positive Elek test with the modified culture medium. A total of 30 of these 61 were tested for toxigenicity in guinea pigs and the results of the animal and plate tests concorded. At least seven cultures could have been reported as non-toxigenic if Elek tests based on media prepared in the conventional way had been the only test available. CONCLUSION: The three procedures described go some way towards meeting the needs of diagnostic laboratories for efficient procedures for distinguishing pathogenic corynebacteria. PMID- 1740515 TI - Bacterial toxins: a possible cause of cot death. AB - AIM: To test the hypothesis that sudden infant death syndrome (SIDS) may be caused by toxins of commonly occurring bacteria in infants lacking developed immunity. METHODS: Nasopharyngeal microbial isolates from 22 pairs of SIDS cases and healthy infants matched for age (by month), sex, and sampling time (by month) were compared for lethal toxigenicity. Crude toxin preparations were made from isolates cultured on dialysis membrane overlaid on agar, and these preparations were then tested for lethality by intravenous injection into 11 day old chick embryos. RESULTS: Fifteen (68%) of the SIDS cases were each found to have at least one lethally toxigenic organism in their nasopharyngeal flora; only eight (36%) of the flora of normal infants included a lethally toxigenic species. CONCLUSION: Infants who have died of SIDS have a significantly higher (p less than 0.05) probability than matched healthy infants of having a lethally toxigenic bacterial species in their nasopharyngeal flora. PMID- 1740516 TI - Plasma viscosity in inflammatory bowel disease. AB - AIMS: To assess the relation of plasma viscosity to disease activity in patients with inflammatory bowel disease. METHODS: Crohn's disease (n = 60) and ulcerative colitis (n = 71) were diagnosed on the basis of typical histological or radiological features. Active Crohn's disease was defined as a Crohn's disease activity index of 150 or over. Active ulcerative colitis was defined as a liquid stool passed three times a day or more with blood. Blood samples were assessed for haemoglobin concentration, total white cell count, platelets, plasma viscosity, erythrocyte sedimentation rate, serum albumin, and C-reactive protein. RESULTS: Plasma viscosity was higher in those with active Crohn's disease compared with those with inactive Crohn's disease or active ulcerative colitis. Plasma viscosity correlated significantly with erythrocyte sedimentation rate, C reactive protein, and platelet count in patients with Crohn's disease. In ulcerative colitis plasma viscosity correlated only with serum C-reactive protein. Plasma viscosity showed a low sensitivity for detecting active Crohn's disease, with 48% of those with active disease having a plasma viscosity within the laboratory reference range. CONCLUSIONS: Plasma viscosity is related to disease activity in Crohn's disease, but is insufficiently sensitive for it to replace erythrocyte sedimentation rate as a measure of the acute phase response in Crohn's disease. PMID- 1740517 TI - Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers. AB - An attempt was made to correct for the effects of coagulometers on the International Sensitivity Index (ISI) in a series of collaborative studies. Modified ISI were derived from the prothrombin time results with coagulometer systems using a range of calibrated plasmas. Two alternative approaches to correction of the ISI were evaluated. The first relied on the consensus orthogonal regression slopes of the prothrombin times for each coagulometer system plotted against the consensus manual results; the second depended on the local individual slope of the prothrombin times for each instrument. The two procedures were compared with the currently recommended method where International Normalised Ratios (INR) are derived from the manual ISI of the thromboplastin. The recommended method gave a significant bias from the manual results with most coagulometers. In contrast, the local correction procedure gave no significant biases, whereas the consensus method did so in a few instances. Both these correction procedures seem more reliable than the recommended method of INR derivation, but the local correction is more accurate and offers a more practical solution by allowing laboratories to determine their own corrected ISI on a range of calibrated plasmas. PMID- 1740518 TI - Early clinical pathologists 4: Rudolf Virchow (1821-1902). PMID- 1740519 TI - Increased serum concentrations of tumour necrosis factor in beta thalassaemia: effect of bone marrow transplantation. AB - AIMS: Serum concentrations of tumour necrosis factor-alpha (TNF) were determined in beta thalassemic patients before and after bone marrow transplantation (BMT) to evaluate whether changes in TNF concentrations after BMT were related to immune mediated complications. METHODS: Serum TNF concentrations were determined by enzyme linked immunoassay (EIA) in paired samples from 71 patients with beta thalassemia before and after BMT. Serial samples from 13 patients were also studied for up to six months after BMT. Forty one normal healthy children matched for sex and age were studied as controls. RESULTS: beta thalassemic patients had high serum TNF concentrations before transplantation compared with controls. These were not related to sex, age, duration of disease, number of blood transfusions, transferrin concentrations or splenectomy. DQw1 positive patients showed significantly lower TNF concentrations than non-DQw1 cases. Patients with severe liver fibrosis had significantly higher TNF concentrations. No correlation was found between TNF values and BMT outcome before transplantation but TNF alpha values fell significantly after BMT. The decrease persisted only in patients with successful engraftment. In serial samples studied for up to six months after BMT, TNF values decreased but in four out of five patients with graft rejection and in all five with acute graft versus host disease (GVHD) sharp increases occurred at the time of clinical symptoms. No correlation was found between the degree of GVHD and serum TNF-alpha concentrations nor between TNF-alpha concentrations after BMT and the presence of bacterial, viral, and fungal infections. CONCLUSIONS: About 50% of beta thalassemic patients have increased serum TNF, and the changes after BMT are related to the occurrence of immune mediate complications. The persistence of low TNF concentrations after successful engraftment may be due to the preparative regimen and the lack of adverse immune reactions. PMID- 1740520 TI - Classical complement activation induced by pregnancy: implications for management of connective tissue diseases. AB - AIMS: To determine the effect of pregnancy on C4d concentrations and to assess whether C4d remains a useful disease activity marker in the management of connective tissue diseases during pregnancy. METHODS: Plasma C3, C4, and C4d concentrations were measured in 83 women at various stages of normal pregnancy and compared with those in 80 non-pregnant controls. RESULTS: C3 concentrations in the pregnant women were significantly raised (p = 0.0001) and the C4 concentrations were reduced (p = 0.0007), and accompanied by a significant increase in C4d (p = 0.0001). The C4d:C4 ratio was higher in the pregnant women (p = 0.0001). CONCLUSIONS: Pregnancy induces activation of the classical complement pathway. C4d concentrations cannot be used to monitor disease activity in patients with connective tissue diseases during pregnancy. PMID- 1740521 TI - Evaluation of two new methods for routine measurement of alkaline phosphatase isoenzymes. AB - AIMS: To evaluate the performance of two new methods for the analysis of alkaline phosphatase (ALP) isoenzymes designed for use in the routine chemical pathology laboratory: pre-incubation with neuraminidase before agarose electrophoresis; and selective precipitation of the bone isoenzyme with wheat germ agglutinin (WGA). METHODS: Serum samples from 39 patients were analysed. Seventeen were from patients with liver disease, eight from patients with bone disease, and 14 from patients with normal ALP activity and no evidence of liver or bone disease. The two new methods were compared with the established method, wheat germ agglutinin affinity electrophoresis. RESULTS: There was good correlation between the neuraminidase and WGA electrophoretic methods. The WGA precipitation method showed negative interference in the measurement of bone isoenzyme activity in samples containing biliary alkaline phosphatase. Both the new methods had advantages of speed and simplicity over the existing method, but cost per test was considerably higher. CONCLUSIONS: The neuraminidase electrophoretic method is a satisfactory alternative to the WGA affinity electrophoretic method, although it is more expensive. The WGA precipitation method cannot be recommended for use with serum samples from patients with suspected liver disease. PMID- 1740522 TI - Experience of a quality assessment scheme for non-laboratory glucose meters. AB - In late 1989 a quality assessment scheme was introduced for glucose meters at 12 non-laboratory sites in a unit of management. The overall monthly imprecision of the meters varied from 3.4% to 17.1%, the highest coefficients of variation being recorded for glucose concentrations outside the range 3-20 mmol/l. In the same period 37% of results fell outside +/- 10% of laboratory set target limits; 13% fell outside +/- 20% of these limits. Participants have been advised of the unreliability of results outside the range 3-20 mmol/l. The main benefit of the scheme has been the improved confidence of users in the results obtained. PMID- 1740523 TI - Audit of catheter urine culture requests. AB - An audit to assess the appropriateness of catheter urine culture requests was carried out for a period of one month. The requests were followed up by members of the Infection Control Team at ward level. The laboratory report had no impact on the removal of the catheter in asymptomatic or symptomatic patients, although the reports did aid antibiotic prescribing in symptomatic patients. PMID- 1740524 TI - Transitional cell carcinoma: a case for collaboration. AB - Urine samples from the greatest proportion of the numerical workload of most clinical microbiology laboratories. During the screening by microscopy, atypical cells were detected which did not conform to the normal cellular morphology found in urinary deposits. These specimens were referred to the Department of Cytopathology for a second opinion. From these referrals a small but significant number of previously undiagnosed transitional cell carcinomas were detected. PMID- 1740525 TI - Symptomatic zinc deficiency in experimental zinc deprivation. AB - An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkaline phosphatase activity. Alcohol induced hepatitis, which was suspected in this subject, may have caused a predisposition to altered zinc metabolism and possible zinc deficiency which was exacerbated by subsequent zinc deprivation. The report supports the value of neutrophil zinc concentration as an indicator of poor zinc status. PMID- 1740526 TI - Notes on necropsy. AB - From the above it can be seen that autopsy is not a grotesque, macabre procedure performed for peculiar and disreputable reasons in a remote corner of the hospital. On the contrary, it is a scientific study designed to forward our knowledge of health and disease by the three primary methods of service, teaching and research. The examination of a dead body is always an emotional procedure. The pathologist and those concerned with frequent performance of autopsies become accustomed to it. To witness an autopsy may cause considerable emotional reaction in inexperienced people. As part of the learning experience, it can be very useful and appropriate staff are welcome to attend by arrangement. As proper protection garments are required and the suitability of viewing certain autopsies may arise, a formal request to the responsible pathologist is necessary. Whatever one's religious beliefs, it may be helpful to think of the deceased person's body as something which he or she has used during life, but which is no longer in any real way the persons once life has departed. The decreased body must be treated with dignity and respect as representing the remains of what was a human being and because of the natural desire of the next of kin that the remains of their relative should so be treated; it is not the person who used the body during life. PMID- 1740527 TI - Comparison of two simple microaerobic atmospheres for cultivation of thermophilic campylobacters. AB - A comparison of a modification of the spirit burn method and one based on the Fortner principle was carried out on 3474 faecal samples from patients with diarrhoea. Of the 96 isolates of Campylobacter, 47 showed equal abundance of growth, regardless of the method used. By using the spirit burn method, however, growth of 33 isolates was significantly increased, and 18 out of those 33 isolates grew only in the spirit burn method atmosphere. The spirit burn method is more effective than the one based on the Fortner principle, it is easy to perform, quick, and cheap. PMID- 1740528 TI - Association between mast cells and myelomonocytes. PMID- 1740529 TI - Distribution of type IV collagen immunoreactivity to assess questionable early stromal invasion. AB - AIMS: To determine if the immunocytochemical delineation of subepithelial basement membrane can be used in the assessment of questionable early invasive cervical carcinoma. METHODS: The distribution of immunoreactive type IV collagen was examined in 15 cervical biopsy specimens in which the reporting pathologist had specifically described difficulty in assessing or excluding early invasion of subepithelial stroma associated with cervical intraepithelial neoplasia (CIN). The results were compared with those from biopsy specimens showing CIN III (N = 8), carcinoma with definite early stromal infiltration (FIGO stage 1a1) (n = 6), and more advanced invasive squamous tumours (FIGO stages 1a2 to 3) (n = 8). In all cases the immunocytochemical findings were assessed in relation to serial sections stained with haematoxylin and eosin. RESULTS: Six of the 15 diagnostically problematic biopsy specimens were considered, on review, to show early infiltration of subepithelial tissue and putative invasive foci were consistently absent in basement membrane. A similar pattern was observed in the "definite" early invasive cases. Eight problematic biopsy specimens were considered to show only in situ neoplasia; five of these had intact though occasionally attenuated basement membrane, three showed focal type IV collagen defects. In the remaining case biopsy trauma precluded further assessment. Basement membrane defects were identified in five of eight cases of CIN III, while three of eight squamous carcinomas showed partial retention of type IV collagen immunoreactivity around invasive tumour cell nests. CONCLUSIONS: Defects in subepithelial basement membrane occur in in situ and invasive neoplasia in the uterine cervix. Immunocytochemical staining for type IV collagen is of limited diagnostic value in the assessment of biopsy specimens with questionable early stromal invasion. PMID- 1740530 TI - Reconstruction of fetuses after dissection. PMID- 1740531 TI - MacPharmacology: a series of computerized study and review programs. PMID- 1740532 TI - Excess synthroid ingestion presenting as congestive heart failure. PMID- 1740533 TI - Effects of chronic amantadine hydrochloride ingestion on its and acetaminophen pharmacokinetics in young adults. AB - The authors studied the effect of chronic amantadine ingestion on its own disposition and that of acetaminophen in five healthy young adults. The half-life of amantadine after 42 days ingestion was 15.1 +/- 2.3 hours and was not different from 14.8 +/- 4.4 hours after an acute ingestion (mean +/- SD). However, chronic amantadine ingestion was associated with an increased apparent volume of distribution for acetaminophen, 1.1 +/- 0.1 L/kg compared with 0.9 +/- 0.1 L/kg, when the two drugs were concurrently ingested after a 2-week washout period. This difference in kinetic distribution was not reflected in terminal acetaminophen half-life, 149 +/- 54 versus 151 +/- 55 minutes for chronic and acute amantadine ingestion, respectively. Plasma acetaminophen clearance with chronic amantadine ingestion (5.8 +/- 2.6 mL/min/kg) was not different from that determined after acute coingestion of both drugs (4.3 +/- 1.1 mL/min/kg). Thus, no change in recommended dose is necessary when these two drugs are coingested. PMID- 1740534 TI - Clinical pharmacokinetics of albendazole in patients with brain cysticercosis. AB - Albendazole pharmacokinetics were studied in eight patients who were receiving albendazole in doses of 15 mg/kg per day for 8 days as treatment of brain cysticercosis. Albendazole was not detected in plasma, but its main metabolite albendazole sulphoxide could be measured. Maximum plasma levels for albendazole sulphoxide ranged from 0.45 to 2.96 micrograms/mL. The half-life of albendazole sulphoxide was between 10 and 15 hours. A double peak was found in three patients. Mean residence time values were from 14 to 20 hours. Plasma levels of albendazole sulphoxide at the steady state showed great intraindividual variability. The results suggest that albendazole can be administered twice daily rather than three times as is currently done. PMID- 1740535 TI - Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A. AB - A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone. PMID- 1740536 TI - The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis. AB - The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups. PMID- 1740537 TI - Pharmacokinetics of tranexamic acid in patients with ulcerative colitis and in healthy volunteers after the single instillation of 2 g rectally. AB - Topically applied antifibrinolytic drugs may be of value in the control of bleeding in active ulcerative colitis. Any impairment of systemic fibrinolysis in this condition, however, is potentially harmful. Since pharmacokinetic data after the rectal administration of tranexamic acid are non-existent, plasma concentration and recovery in the urine were recorded after a single dose of 2 g tranexamic acid given rectally to five patients with ulcerative colitis and to five healthy volunteers. The median area under the curve was, for the volunteers, 7.64 mg/L x hr (range: 4.43-11.56) and, for the patients, 13.84 mg/L x hr (range: 9.32-50.22) (P less than .05). The median 24-hour recovery in the urine was 0.8% (0.3-1.1) and 2.7% (1.1-4.0), respectively (P less than .05). The median peak plasma concentration was, for the volunteers, 0.40 mg/L (range: 0.20-0.69) 6 hours after administration and, for the patients, 1.10 mg/L (range: 0.53-2.90) 5 hours after administration (P less than .05). The plasma concentrations and recovery in the urine that were observed in the patients and volunteers were low compared with those seen after oral intake of the same dose. The plasma concentrations did not reach levels that were considered liable to impair systemic fibrinolysis. PMID- 1740538 TI - Antihypertensive and metabolic effects of single and combined atenolol regimens. AB - The antihypertensive and metabolic effects of placebo (PL), a fixed combination of hydrochlorothiazide (25 mg) and triamterene (50 mg) (HCTZ/TRI), atenolol (25 mg) (Atc-25), atenolol (50 mg) (Ate-50) and their combination with HCTZ/TRI given once daily, were tested on 256 patients with mild-to-moderate essential hypertension. After 3 weeks of PL monotherapy, 43 patients were randomized to PL (group 1), 41 patients to HCTZ/TRI (group 2), 44 patients to Ate-25 (group 3), 42 patients to Ate-50 (group 4), 43 patients to Ate-25/HCTZ/TRI (group 5), and 43 patients to Ate-50/HCTZ/TRI (group 6) in a double-blind parallel design study and were followed for 4 weeks. At the end of week 7, those patients who were randomized to groups 5 and 6 were allowed to continue for an additional 12 weeks, if their arterial pressure was satisfactorily controlled. Complete blood counts, blood chemistries, urinalyses, and electrocardiograms were done initially and during the study. Monotherapy with HCTZ/TRI, Ate-25, and Ate-50 had significant and equal antihypertensive effects compared with placebo. (P less than .01). However, the combination of Ate-25/HCTZ/TRI and Ate-50/HCTZ/TRI resulted in further reduction of arterial pressure with the effect being greatest with Ate 50/HCTZ/TRI (P less than .001). Patient groups 3 through 6 had also slower heart rates compared with groups 1 and 2 (P less than .01). Mild, but statistically significant, increases in BUN, glucose, triglycerides, and uric acid were noted in groups 2, 5, and 6 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740539 TI - Transcranial Doppler to evaluate the effects of antihypertensive medication on cerebral blood flow velocity. AB - The effect of oral nifedipine on cerebral blood flow velocity was studied in six elderly hypertensive patients using transcranial Doppler. Serial measurements of blood pressure (BP), middle cerebral artery (MCA) flow velocity and nifedipine serum concentrations were obtained over an 8-hour period. The authors found a significant inverse relationship between MCA velocities and nifedipine concentrations, independent of BP changes. These results are consistent with a direct vasodilatory effect of nifedipine on cerebral vessels and support the use of TCD in pharmacodynamic investigations of the cerebral vasculature. PMID- 1740540 TI - Evaluation of quinapril on regional blood flow and cardiac function in patients with congestive heart failure. AB - Quinapril, a nonsulfhydryl ACE inhibitor, was evaluated in ten New York Heart Association (NYHA) functional class (FC) II-III CHF patients to determine its effects on regional blood flow [effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), hepatic blood flow (HBF), hepatic vascular resistance (HVR), segmental limb pressure (SLP), creatinine clearance (CRCL)] and cardiac function [left ventricular ejection fraction (LVEF)]. Previous vasodilator therapy was withdrawn 2 weeks before baseline measurements. Stable regimens of digoxin and diuretics were continued throughout the study. ERPF was assessed using p-aminohippurate (PAH), HBF by indocyanine green (ICG) clearance, and LVEF by radionuclide scintography. Segmental limb pressures were measured by Doppler flow detection. Measurements were performed at baseline (B) and after 4 weeks of quinapril therapy (10 mg BID). Quinapril increased renal (P less than 0.05) and hepatic blood flow (P = 0.06) and significantly reduced renal and hepatic vascular resistance. Glomerular filtration rate and left ventricular ejection fraction were unchanged. Mean arterial pressure and brachial segmental pressures decreased without change in heart rate. Noninvasive cardiovascular assessments indicate that quinapril improves regional blood flow while exhibiting no change in left ventricular ejection fraction, in patients with NYHA FC II-III CHF. PMID- 1740541 TI - Pharmacodynamic and pharmacokinetic evaluation of a new transdermal delivery system with a time-dependent release of glyceryl trinitrate. AB - The pharmacokinetics of glyceryl trinitrate (GTN) and its main metabolites as well as the hemodynamic effects of a new transdermal delivery system (TDS) were investigated in ten healthy male volunteers using a single blind, placebo controlled study design with an application period of active drug of 4 successive days. The adhesive-type matrix system contains 20-mg GTN and released about 75% in a time-dependent manner. The plasma concentrations of GTN and its metabolites 1-2- and 1-3 glyceryl dinitrate reflected the time-dependent release with higher plasma concentrations during the first 12 hours than during the second 12 hours. Continuous administration of the TDS, which released 15 mg GTN/day, caused an accumulation of GTN in the plasma (about 70% greater AUC at the fourth day in comparison with the first day). The total effect per dose on the a/b-ratio of the digital pulse (height of the peak of the systolic wave divided by height of the peak of the dicrotic wave) and the reflex tachycardia were diminished by about 50% and 37%, respectively, at the fourth treatment day. The effect on systolic blood pressure measured under orthostatic conditions was blunted already 8 hours after the first application. The effect of sublingually administered GTN on digital pulse was attenuated during administration and also 1 hour after removal of the last TDS. The effect was restored 8 to 12 hours after removal of the TDS. Thus, the discontinuous release of GTN from the new system does not prevent the decline of hemodynamic efficacy during continuous therapy. PMID- 1740542 TI - Effect of cimetidine administration on the pharmacokinetics of pirmenol. AB - The potential for a drug-drug interaction between pirmenol, an extensively metabolized antiarrhythmic agent, and cimetidine, an inhibitor of hepatic drug metabolizing enzymes, was evaluated in eight healthy adults. A single 150-mg oral dose of pirmenol was administered on study days 1 and 8 and oral cimetidine, 300 mg QID, was administered on study days 4 through 11. Plasma and urine samples were collected after each pirmenol dose for determination of pirmenol concentration. Mean pirmenol concentration-time curves and pharmacokinetic parameters, including elimination rate constant, were not significantly altered by concomitant administration of cimetidine. PMID- 1740543 TI - Development of the olfactory nerve in the clawed frog, Xenopus laevis: II. Effects of hypothyroidism. AB - Quantitative and morphological data were obtained on developing olfactory axons in normal and hypothyroid larvae of the African clawed frog Xenopus laevis. Hypothyroid larvae were produced by rearing the animals, beginning at stage 48, in a 0.01% solution of propylthiouracil (PTU), a treatment that blocks synthesis of thyroid hormone. These PTU-treated larvae were compared to their age-matched siblings when these siblings reached stage 52 (premetamorphic larvae; prior to synthesis of thyroid hormone), stage 57 (late premetamorphic larvae; after the onset of thyroid hormone synthesis), or stage 58 (larvae at the onset of metamorphic climax; thyroid hormone levels continue to rise). The number of olfactory axons did not differ between stage 52 control animals and the age matched, PTU-treated animals, but there were only about half the number of axons in the PTU-treated animals that were age-matched to the stage 57 or 58 controls. Thus, PTU had no effect on olfactory axon number prior to the normal rise in thyroid hormone levels. But PTU significantly reduced the normal increase in olfactory axon number compared to stage 58 control larvae, whose thyroid hormone levels are high. While PTU also produced some changes in several other body measurements, the effect on the olfactory axons was the most consistent and prominent. The results presented here support our previous findings that thyroid hormone plays a significant role in the development of the olfactory system in Xenopus. PMID- 1740544 TI - Spatio-temporal patterns of retinal ganglion cell death during Xenopus development. AB - During development of the retina in mammals and birds, most retinal ganglion cells (RGC) that are produced are eliminated later in development by cell death. In lower vertebrates, however, such massive cell death has not been observed; total ganglion cell number increases linearly during most of development. Using 3H-thymidine or 5-bromodeoxyuridine labeling of retinal cell nuclei, we have been able to identify postmitotic RGC populations in Xenopus central retina at different developmental stages and follow their fate during development to postmetamorphic stages. RGC populations that become postmitotic between embryonic stages 32 and 49, during the initial stages of retinal growth, lose 40-77% of their cells during metamorphosis (approximately 4,000-5,000 cells). Twenty percent of the RGC present at stage 54, which later disappear, represent the same population of dying RGC that were present at stage 49. This suggests that the ganglion cells that became postmitotic between stage 49 and 53/54 show no apparent decline in numbers during metamorphosis. Since thyroxine is known to stimulate an increase in RGC number as well as the extent of fiber projection on the tectum, we suggest that this reduction in RGC numbers is not due to thyroxine induced neuronal cell death. After stage 54, however, binocular vision develops in Xenopus (Keating, '74) and ipsilateral fibers begin to grow into thalamic visual neuropils (Hoskins and Grobstein, '85). We suggest, therefore, that as in mammals, in which RGC elimination correlates with binocular segregation of contralateral and ipsilateral retinal axons in visual centers, a similar process may occur in the frog among those RGC projecting to thalamic visual neuropils. PMID- 1740545 TI - Immunohistochemical evidence for transient expression of fibronectin in the developing dorsal lateral geniculate nucleus of the ferret. AB - In recent years, the important role of the extracellular matrix in neural development has been increasingly recognized. In order to begin to examine what role might be played by the extracellular matrix in the developing dorsal lateral geniculate nucleus (dLGN), the present study used immunocytochemistry to assess the distribution of a recognized extracellular matrix molecule, fibronectin (FN), during postnatal development of the ferret dLGN. Prior to the segregation of cell layers, no clear pattern of FN distribution can be distinguished within the dLGN. By P16, when layers A and A1 are separated by an interlaminar space, FN is localized in that space. By P24, FN is present not only between layers A and A1, but also within layers A and A1 as bands parallel to the laminar borders. These bands appear to correspond spatially and temporally to the development of sublaminar boundaries in the ferret (Hahm and Sur, Neurosci Abstr 14:460, 1988). By the end of the first postnatal month, immunoreactivity is diminished but still present. FN is no longer present at P44 or in the adult. Adjacent sections were incubated with antiserum to glial fibrillary acid protein (GFAP). When a laminar pattern of GFAP can be distinguished, it coincides with the interlaminar distribution of FN. The findings described here are consistent with a role for FN in the development of a laminar organization in the dLGN. PMID- 1740546 TI - Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area: I. Descending projections. AB - The present study describes the anatomical organization of projections from functionally defined cell groups of the lateral hypothalamic area. Cardiovascular pressor and depressor sites were identified following microinjection (5-50 nl) of 0.01-1.0 M L-glutamate or D,L-homocysteate into the anesthetized rat. Subsequent injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or wheat germ agglutinin horseradish peroxidase (WGA-HRP) were made into pressor or depressor sites and their connections with the brainstem and spinal cord were traced. Decreases in blood pressure (10-45 mmHg) and heart rate (20-70 bpm) were elicited from tuberal (LHAt) and posterior (LHAp) regions of the lateral hypothalamic area (LHA). Depressor neurons in the LHAt have descending projections to the central gray, dorsal and median raphe nuclei, pedunculopontine tegmental nucleus, pontine reticular formation, medial and lateral parabrachial nuclei, laterodorsal tegmental region, and medullary reticular formation including the region of the lateral tegmental field, nucleus ambigous, and rostrocaudal ventral lateral medulla. In contrast, descending projections from depressor neurons in the LHAp have dense terminal fields in the rostral, middle, and commissural portions of the nucleus of the solitary tract and the lateral tegmental field as well as the ventrolateral central gray, pedunculopontine tegmental nucleus, and medial and lateral parabrachial nuclei. Both the LHAt and LHAp have light projections to the intermediate region of the cervical and thoracic spinal cord. Increases in blood pressure (10-40 mmHg) and heart rate (20-70 bpm) were elicited almost exclusively from neurons located medial to the LHAt and LHAp in a region surrounding the fornix, termed the perifornical area (PFA). Pressor cells in the PFA have descending projections to the central gray, dorsal and median raphe nuclei, laterodorsal tegmental nucleus, and Barrington's nucleus as well as a light projection to the commissural portion of the nucleus of the solitary tract and the intermediate region of the cervical and thoracic spinal cord. The retrograde labeling observed in the WGA-HRP studies indicates that cells in most terminal fields have reciprocal projections to the pressor and depressor regions of the LHA. The results demonstrate that groups of neurons in the lateral hypothalamus with specific cardiovascular function have differential projections to the brain stem. PMID- 1740547 TI - Response of retinal terminals to loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat. AB - We have used the neurotoxin kainic acid to produce rapid degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN) of the adult cat. This degeneration mimics the rapid loss of geniculate neurons seen after visual cortex ablation in the neonate. Subsequent anterograde transport of horseradish peroxidase injected into the eye was used to reveal the projection patterns of retinal ganglion cell axons at different survival periods after the kainic acid injection. The density of retinal projections to the degenerated regions of the geniculate was reduced considerably at 4 and 6 months survival, but at 2 months was not significantly different from normal. The laminar pattern of projections to degenerated regions of the geniculate did not change in any animals studied, even when an adjacent lamina contained surviving cells. Electron microscopic examination of degenerated dLGN revealed intact retinal (RLP) and RSD terminals at all survival times, although the density of terminals appeared much reduced when compared to controls. Some RLP terminals exhibited the "dark reaction" of degeneration and these degenerating terminals were most numerous at 2 months survival. These findings demonstrate that, in response to degeneration of their usual target cells, mature retinal ganglion cells with withdraw their axon terminals from these regions of degeneration. We conclude that mature retinal ganglion cells continue to be dependent on target integrity for the maintenance of a normal axonal arborization. PMID- 1740548 TI - Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis and brain of the big brown bat, Eptesicus fuscus. AB - Little is known about the immunohistochemistry of the nervous system in bats. This is particularly true of the nervus terminalis, which exerts strong influence on the reproductive system during ontogeny and in the adult. Luteinizing hormone releasing hormone (LHRH) was visualized immunocytochemically in the nervus terminalis and brain of juvenile and adult big brown bats (Eptesicus fuscus). The peripheral LHRH-immunoreactive (ir) cells and fibers (nervus terminalis) are dispersed along the basal surface of the forebrain from the olfactory bulbs to the prepiriform cortex and the interpeduncular fossa. A concentration of peripheral LHRH-ir perikarya and fibers was found at the caudalmost part of the olfactory bulbs, near the medioventral forebrain sulcus; obviously these cells mediate between the bulbs and the remaining forebrain. Within the central nervous system (CNS), LHRH-ir perikarya and fibers were distributed throughout the olfactory tubercle, diagonal band, preoptic area, suprachiasmatic and supraoptic nuclei, the bed nuclei of stria terminalis and stria medullaris, the anterior lateral and posterior hypothalamus, and the tuber cinereum. The highest concentration of cells was found within the arcuate nucleus. Fibers were most concentrated within the median eminence, infundibular stalk, and the medial habenula. The data obtained suggest that this distribution of LHRH immunoreactivity may be characteristic for microchiropteran (insectivorous) bats. The strong projections of LHRH-containing nuclei in the basal forebrain (including the arcuate nucleus) to the habenula, may indicate close functional contact between these brain areas via feedback loops, which could be important for the processing of thermal and other environmental stimuli correlated with hibernation. PMID- 1740549 TI - A morphological correlate of target recognition by regenerating motor axons in the cockroach. AB - A specific cell recognition process during regeneration of severed axons of identified cockroach motor neurons eventually leads to the reformation of the original innervation pattern of target muscles in the leg. This occurs even though, at early times after nerve crush, the multiple branches of each regenerating axon grow into both appropriate and inappropriate muscles. In this study, we sought to examine whether there are any structural differences between regenerating axon branches in appropriate and inappropriate muscles that could lead to an understanding of why only those in inappropriate muscles are eliminated. A neuron subset-specific monoclonal antibody, NSS-2A, which labels the inhibitory motor neurons, was used to make their axon branches visible at various times after nerve crush. In inappropriate muscles, these axons grow primarily parallel to the muscle fibers and are later eliminated. In the appropriate muscles, these axon branches initially also grow parallel to the muscle fibers, but subsequently grow many interstitial collaterals. The formation of the collateral branches is a morphological correlate of the specific interaction of a neuron with its appropriate muscle. The simultaneous occurrence of axonal elimination and collateral sprouting supports the idea that the two processes are causally related, as suggested by the sibling neurite bias hypothesis. PMID- 1740550 TI - Radiopacity and physical properties of titanium-polymethacrylate composite. AB - Titanium-polymethacrylate composite was prepared as an x-ray-opaque filler for composite core materials. The base monomers of the composite were 2,2-bis [4-(3 methacryloyloxy-2-hydroxypropoxy) phenyl] propane (Bis-GMA) and triethyleneglycol dimethacrylate (TEGDMA). Pure titanium powder was used as a radiopaque element. Two functional methacrylates--isopropyl dimethacryloyl isostearoyl titanate (KR 7) and 4-methacryloyloxyethyl trimellitate anhydride (4-META)--were adopted as couplers of titanium powder. The radiopacity of composites was determined in terms of their equivalent thickness of aluminum per unit thickness of material. Compressive and transverse strengths of the composites were measured by use of coupled and untreated titanium fillers. The composites that contained 70% and 80% titanium by weight showed more radiopacity than enamel and less than amalgam. Radiopacity was controlled by the content of titanium filler in the composite. The decrease in compressive and transverse strengths of the composites was 0.7 to 15.9% and 43.7 to 52.9%, respectively, after one year's immersion in water. The decrease in transverse strength was remarkable; however, this deterioration was diminished by use of both KR-7 and 4-META as couplers for titanium. Thus, prepared titanium-polymethacrylate composite may be used as a radiopaque composite filler for self-curing composite core materials. PMID- 1740551 TI - The effect of carbamide-peroxide gel on the shear bond strength of a microfil resin to bovine enamel. AB - Cylinders of a visible-light-cured microfil resin were formed on, and bonded to, the flattened labial enamel surfaces of young bovine incisor teeth which had previously been subjected to four different treatments: (1) immersion in 10% carbamide-peroxide gel, pH 4.7, for three h; (2) immersion in 10% carbamide peroxide gel, pH 4.7, for six h; (3) immersion in 10% carbamide-peroxide gel, pH 7.2, for three h; and (4) immersion in 10% carbamide-peroxide gel, pH 7.2, for six h. For each experimental group, a control group of resin-bonded to saline immersed teeth was prepared. In addition, two groups, prepared according to treatment 4, were leached in distilled water for one and seven d, respectively, prior to resin application. Specimens were stored in distilled water at 37 degrees C for seven d prior to shear-bond-strength testing. A total of 90 teeth was tested. Statistical analysis of the results indicated that there was a highly significant reduction in the shear bond strength to carbamide-peroxide-treated enamel as compared with that to saline-treated enamel. The effects of duration of peroxide treatment and pH, as well as the interaction term, were not statistically significant. Leaching of the peroxide-treated enamel in water for either one or seven d prior to resin application restored the adhesiveness of the enamel. Scanning electron microscopic examination of randomly selected, fractured test specimens indicated that the peroxide-induced reduction in enamel adhesiveness was related to alterations in both attachment-surface area at the resin-enamel interface and resin quality. PMID- 1740552 TI - The effect of sucrose on plaque pH in the primary and permanent dentition of caries-inactive and -active Kenyan children. AB - The hypothesis that the Stephan pH responses of dental plaque would be different in caries-active and -inactive individuals was tested in 20 seven-year-old and 19 14-year-old Kenyan children. In each age group, half the children had greater than or equal to 2 dentin cavities; the other half had no such lesions. With a palladium-touch microelectrode, interdental plaque pH was monitored between m1/m2 in each quadrant in the primary dentition and in the four molar/premolar regions in the permanent dentition. pH was also monitored in caries cavities in the occlusal surfaces of lower first molars and on the tongue. pH was measured before and up to 60 min after the children rinsed with 10 mL of 10% sucrose. Caries status of the individual was unrelated to plaque pH in comparable non-carious sites in both of the age groups. The pH minimum in the maxilla was about 0.5 pH units lower than that in the mandible. Active occlusal caries lesions had a resting pH value of about 5.5, about 1 pH unit lower than that of sound surfaces. The pH dropped to about 4.5 in caries lesions and recovered slowly. In sound occlusal sites, a pH drop to about 6.0 was followed by a relatively rapid return to the resting value. Thus, when the mean values were considered, the classic Stephan curve response was evident. However, when the pH changes at single sites were considered at various time intervals, a substantial, erratic fluctuation was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740553 TI - The effect of chlorhexidine varnish treatment on salivary mutans streptococcal levels in child orthodontic patients. AB - A chlorhexidine dental varnish was applied to the teeth of 26 children, ten to 17 years of age, in an attempt to limit the increase in colonization by mutans streptococci that normally accompanies the placement of fixed orthodontic appliances and to assess the acceptance of the application procedure. Despite the insertion of the appliances in the month following the varnish application, the numbers of detectable salivary mutans streptococci in the children were found to remain significantly lower than baseline values for seven months (p less than 0.01). Among the 26 children, 16 exhibited high counts (greater than 2.5 x 10(5) cfu/mL saliva) at baseline, but none exhibited such counts until three months post-treatment, when one child did. By seven months, eight children had high counts. No significant difference in effectiveness was observed between varnish formulations containing 10% or 20% chlorhexidine acetate, or between children of different ages or past caries experience. The lack of drop-outs and the results of a questionnaire indicated that acceptance of the treatment by the children was excellent. The study indicates that chlorhexidine varnish therapy was acceptable to the children and was effective in suppressing oral mutans streptococcal levels for long periods, even when used prior to the placement of fixed orthodontic appliances. PMID- 1740554 TI - Expression of type I collagen pro-alpha 2 chain mRNA in adult human permanent teeth as revealed by in situ hybridization. AB - The expression of the gene COL1A2, coding for the pro-alpha 2 chain of type I pro collagen, was analyzed in fully developed human permanent teeth. The teeth were fixed with formalin, demineralized with EDTA for about ten weeks, and embedded in paraffin. Pro-alpha 2(I) mRNA was localized in the sections by in situ hybridization, with use of [35S)]-labeled single-stranded RNA probes. The amount of mRNA for pro-alpha 2(I) collagen chain, as indicated by the relative densities of silver grains and the grain counts per cell in autoradiography, was high in odontoblasts, whereas in pulpal fibroblasts it was low. High levels of pro-alpha 2(I)mRNA expression were also present in those odontoblasts which had elaborated new dentin matrix in response to dental caries. Expression in the periodontal ligament, including the cementoblast layer, was slightly stronger than that in odontoblasts. The intense expression of pro-alpha 2(I) mRNA in odontoblasts of adult teeth suggests that even after the completion of primary dentin formation, they continue to synthesize heterotrimeric type I collagen molecules. Cell type specific differences in the expression of pro-alpha 2(I) mRNA imply that type I collagen probably plays a major role in the regulation of the structure and function of dental tissues. Finally, in situ hybridization enabled pro-alpha 2(I) collagen mRNA to be detected in tissue sections even after prolonged demineralization, and thus it proved to be a valuable technique for analysis of gene expression in adult dental tissues, as shown here for COL1A2. PMID- 1740555 TI - Fatty acids of healthy and periodontally diseased root substance in human teeth. AB - In this comparative study, samples of root substance from healthy and periodontally diseased human teeth were analyzed for fatty acids by means of a gas-chromatographic technique. The sample preparation procedure allowed specimens from individual teeth to be analyzed. The content of the fatty acids C16:0, C16:1, C18:0, and C18:1 in the superficial layer of the periodontally diseased teeth was significantly higher than that of healthy teeth. In the inner layer, there was no such difference. Four different 3-hydroxy fatty acids (3-OH C14:0, 3 OH C15:0, 3-OH C16:0, and 3-OH C17:0) were identified by combined gas chromatography/mass-spectrometry in the tooth substance of periodontally diseased teeth. This indicates the presence of lipid A, which is the toxic component of bacterial lipopolysaccharides. PMID- 1740556 TI - Electromyographic heterogeneity in the human masseter muscle. AB - The complex, pennate architecture of the human masseter muscle points to a functional division into more than the commonly distinguished deep and superficial parts. In this study, the possible existence of regional differences in activation was examined. EMG activity was registered in three deep and three superficial regions with the use of bipolar fine-wire electrodes. Recordings were made during different static bite tasks, in specified directions, and with a specified bite-force magnitude. A linear bite-force/EMG relationship was observed. Furthermore, it appeared that muscle regions showed a different pattern of change in activity as a function of bite-force direction. Heterogeneity was nearly absent in anteriorly-, anteriomedially-, and medially-directed bites, but became increasingly obvious in the other bite-force directions. The posterior deep region showed the most aberrant activation pattern, which was almost opposite that from the other regions. This part was fully active in posterolaterally-directed bites. The posterior superficial region showed the largest variability in activity as a function of bite-force direction. The results point to a functional partition of the masseter muscle in at least three parts: anterior deep, posterior deep, and superficial. A further subdivision of the superficial portion might be present, but was not as obvious as the division of the deep masseter. PMID- 1740557 TI - A light and electron microscopic anterograde WGA-HRP tracing study on the sensory innervation of junctional and sulcular epithelium in the rat molar. AB - The sensory innervation of junctional and oral sulcular epithelium was investigated by use of anterograde transport of wheat-germ agglutinin-horseradish peroxidase from the trigeminal ganglion. By light microscopy, labeled intra epithelial nerve fibers were observed forming a dense plexus in the apical two thirds of the junctional epithelium, with some fibers located near the enamel space. Occasional fibers extended coronally to the sulcus bottom. By electron microscopy, labeled intra-epithelial axon terminals or varicosities were demonstrated to be in close contact with both junctional epithelial cells and neutrophils. These varicosities, which were occasionally surrounded by the cytoplasmic processes of epithelial cells or neutrophils, frequently contained large granular and small clear vesicles. In contrast to the junctional epithelium, the oral sulcular epithelium was sparsely innervated, except for the transition region between the oral sulcular epithelium and the junctional epithelium, where a dense innervation by labeled intraepithelial fibers was found. These fibers extended as far as the stratum spinosum. Electron microscopy revealed mitochondria-filled profiles of varicosities between epithelial cells. This study shows differences in the distribution and ultrastructure of sensory nerves between the junctional and oral sulcular epithelia, and further provides morphological evidence that sensory nerves in the junctional epithelium come into contact not only with epithelial cells but also with neutrophils. PMID- 1740558 TI - Factors affecting blood mercury concentrations in practicing dentists. AB - It has been suggested that mercury vapor may be transformed into highly toxic organomercury compounds by micro-organisms in the oral cavity and gastrointestinal tract. If this hypothesis is correct, practicing dentists might be expected to have concentrations of organic mercury in their blood higher than that found in non-dentists. Blood mercury concentrations of practicing dentists and non-dentists were determined by means of cold-vapor atomic absorption spectrophotometry. Potential sources of mercury exposure were identified in both dentists and non-dentists through a questionnaire completed at the time of sampling. Concentrations of total and inorganic blood mercury were significantly higher in dentists than in non-dentists. The organomercury concentrations of the two groups were not statistically different (p greater than or equal to 0.05). The high concentration of inorganic mercury in the blood of dentists was not related to the organomercury level, suggesting that biotransformation of inorganic mercury to organomercury does not occur in vivo. However, the concentration of blood organomercury was positively correlated with the frequency of fish consumption. There was no correlation between the number of amalgam restorations and the concentration of inorganic blood mercury for both groups. Accidental mercury spills in the dental operatory may contribute most to the concentration of inorganic blood mercury in the blood of dentists. PMID- 1740559 TI - An in vitro model for assessment of fluoride uptake from glass-ionomer cements by dentin and its effect on acid resistance. AB - This investigation presents an experimental model for studying interactions of glass-ionomer cements (GICs) with bovine dentin slabs. Fluoride incorporation was studied with five serial abrasion biopsies, each being approximately 10 microns thick. The time of interaction was a very important parameter, indicating continuous fluoride release from the GIC and diffusion into dentin over a 30-day period. Expressed in mass per volume (mg F/cm3), the fluoride incorporation reached 12.0 mg at the first and 2.5 mg at the fifth layer, several times greater than the baseline of 0.27 mg/cm3 in bovine dentin. A subsequent test of acid resistance in a lactic acid buffer (pH 4.0), followed by microradiography of lesions, showed a characteristic 40-microns-wide acid-resistant zone on surfaces exposed to the GICs. In contrast, the untreated control surfaces had lesions demineralized evenly from the surface to the intact tissue, without the higher density zone at the surface of the lesion. The model seems promising for screening fluoride incorporation into dentin from fluoride-releasing dental materials. PMID- 1740560 TI - Dental school admission and graduation requirements. PMID- 1740561 TI - Educational goals and research directions in endodontics. PMID- 1740562 TI - Treatment of glabellar frown lines with C. botulinum-A exotoxin. AB - Eighteen patients with glabellar frown lines were treated with C. botulinum-A exotoxin. Sixteen of the 17 patients followed showed improvement for periods ranging from 3 months to 11 months. Side-effects were minimal and transient. Because C. botulinum-A exotoxin therapy of glabellar frown lines treats the underlying cause of these lines, it is more effective than soft tissue augmentation although this improvement is temporary. Treatment with C. botulinum A exotoxin is a simple, safe procedure. PMID- 1740563 TI - Clinical predictors of malignant pigmented lesions. A comparison of the Glasgow seven-point checklist and the American Cancer Society's ABCDs of pigmented lesions. AB - Reducing morbidity and mortality from malignant melanoma is the greatest challenge facing dermatology today. We present a comparison of the Glasgow seven point checklist and the American Cancer Society's ABCDs of pigmented lesions for detecting early melanomas. Logistic regression analysis showed that the Glasgow checklist (N = 205 lesions) contained two significant variables (irregular outline, P = .001, relative odds = 10.9; diameter greater than 1 cm, P = .005, relative odds = 6.7) for differentiating benign from malignant pigmented lesions whereas a three-point version of the ABCDs (N = 192 lesions) had three significant variables (irregular outline, P = .001, relative odds = 9.3; diameter greater than 6 mm, P = .008, relative odds = 5.5; variegation, P = .05, relative odds = 3.7). All six melanomas scored 3 out of 3 on the ABCD scale for a sensitivity of 1.00 and specificity of 0.98 at a threshold of 3 out of 3. Patients rarely sought dermatologic consultation because of these predictors but often sought help for nonsignificant reasons such as inflammation (P = .93), color change (P = .84), itch (P = .72), and increasing size (P = .38). The simpler three-point scale at a threshold of two had equal specificity (0.88 versus 0.94) and better sensitivity (0.73 versus 0.44) than the Glasgow seven point checklist at the recommended threshold of three out of seven. We therefore recommend that the American public be better educated about the ABCDs to help increase self-referral so that early melanomas can be found and eradicated. PMID- 1740564 TI - The ice-saline-Xylocaine technique. A simple method for minimizing pain in obtaining local anesthesia. AB - Prior to skin surgery, localized cryoanesthesia is initially obtained utilizing Cryogel packs before local anesthesia injection, minimizing or abolishing pain from the piercing of the skin by the injection needle. The surgical field is then infiltrated with benzyl alcohol-containing normal saline, a painless solution producing moderate local anesthesia. Subsequently, a stronger anesthetic containing a vasoconstrictor or other desired additives can be infiltrated without significant patient discomfort. This simple three-step method has resulted in excellent patient acceptance, and is potentially useful for a wide range of surgical procedures and medical specialties. PMID- 1740565 TI - Microsurgical treatment of nasolabial and glabellar wrinkles. AB - Nasolabial and glabellar wrinkles have been treated using a new microsurgical technique. This technique consists of two steps, both performed under a microscope: 1) microsurgical peeling of tissue surrounding the wrinkle, and 2) direct excision of the wrinkle. This procedure was performed on approximately 30 patients. All results showed effective diminishing of the treated wrinkle with almost no conspicuous scarring. PMID- 1740566 TI - Varicose veins--primary treatment with sclerotherapy. A personal appraisal. AB - Varicose veins are a very common condition that presents in a variety of forms. Treatment modalities are variant and beneficial. The author reports on an experience of 25 years treating 20,000 patients using surgery and sclerotherapy with particular results using morrhuate sodium. PMID- 1740567 TI - Postsclerotherapy hyperpigmentation. The role of serum ferritin levels and the effectiveness of treatment with the copper vapor laser. AB - Cutaneous pigmentation is a common complication of sclerotherapy of dilated lower limb veins. Histologic examination has shown that the pigment is due to hemosiderin deposition predominantly in the superficial dermis. Optimal technique will reduce the incidence of pigmentation but it is likely that patient factors such as total body iron storage may explain why some patients are more prone to develop pigmentation. Traditional exfoliation therapies have not given reliable reproducible results and there is need to develop an effective treatment without adverse sequelae. In this study 16 patients with refractory postsclerotherapy pigmentation were treated with the copper vapor laser. Within 3 months of treatment 11 (69%) had significant clearing of the pigmentation. Four (25%) had slight improvement and one patient had no discernible improvement. No adverse sequelae were reported or observed. The treated patients and 16 matched control patients who had not developed pigmentation were investigated with serum iron, ferritin and transferrin levels. There was a trend towards higher serum iron and ferritin levels and lower transferrin levels in the patients who developed pigmentation compared with those who did not develop this sequela. This trend was statistically significant for ferritin levels in patients 50 years of age and younger. The results indicate that serum ferritin may be a good indicator of susceptibility to postsclerotherapy pigmentation. PMID- 1740568 TI - Ambulant minisurgical phlebectomy. PMID- 1740569 TI - Office varicose vein surgery under local anesthesia. AB - Varicose veins of any size (except telangiectasia) and in any site of the lower limb (except the saphenofemoral junction) can be avulsed through multiple 0.5-mm (or larger) incisions under local infiltration anesthesia (Muller's technique). When necessary, high ligation, division, and stripping of the proximal long saphenous vein can also be performed under local anesthesia. It is thus possible to treat even the most complex varicose cases with outpatient office-based surgery. PMID- 1740570 TI - Posterior composite restorations. PMID- 1740571 TI - Air-driven handpieces and air emphysema. Council on Dental Materials, Instruments and Equipment; American Association of Oral and Maxillofacial Surgeons. PMID- 1740572 TI - Oral candidal infection and denture stomatitis: a comprehensive review. AB - Denture stomatitis rarely occurs without at least one predisposing factor that lowers patient resistance. A new disinfection technique for dentures and oral tissue may eliminate topical or anti-fungal drug use. PMID- 1740573 TI - Oral health of patients with Alzheimer's disease. AB - Generally healthy, unmedicated patients with Alzheimer's disease have few but significant changes in their oral health. Study results reinforce preventive oral hygiene for these patients. PMID- 1740574 TI - Patient maintenance of esthetic restorations. AB - There are probably as many ways to maintain esthetic restorations as there are restorations. After esthetic treatment is completed, schedule a mandatory postoperative appointment to make certain that whatever technique the patient uses is effective. At the postoperative visit, it should be apparent that the patient's tissue is healthy. If the tissue has not healed, some change in home care or additional periodontal or restorative treatment may be necessary. There are virtually hundreds, perhaps even thousands of home plaque removal devices. The ones mentioned here have worked for us and are therefore discussed. It isn't the type of device that is critical, however, but patient compliance. The described regimens have worked effectively for us in overcoming this obstacle of compliance. Appropriate recall visits with the hygienist should be made at one- to six-month intervals. In the final analysis, your success with esthetic restorations may well depend on your patients' success with esthetic maintenance. PMID- 1740575 TI - Reasons for local anesthesia failures. AB - U.S. dental practitioners administer about 4,000,000 local anesthetic blocks and infiltrations annually. The failure rate to achieve adequate anesthesia for the procedure is estimated to be 5 percent to 15 percent. This article describes five different categories of failures and suggest ways to troubleshoot them. PMID- 1740576 TI - Why do most GPs shun periodontics? PMID- 1740577 TI - Diagnosing and managing oral candidiasis. AB - The red to white lesions of oral candidiasis are easily treated with any of several antifungal medications. But predisposing systemic conditions, such as diabetes mellitus or human immunodeficiency virus infection, should be ruled out as contributing factors. PMID- 1740578 TI - It's time for action on licensure. PMID- 1740579 TI - Firing an employee, how to make the process easier and stay out of court. PMID- 1740580 TI - Dental fees and inflation: good news or bad news? PMID- 1740581 TI - The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma. AB - It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (approximately 60 L/min) versus low (approximately 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, greater than 1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (+/- SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 +/- 0.51 and 1.84 +/- 0.30, respectively (p less than 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 +/- 0.35 and 3.86 +/- 1.25, respectively, compared to 0.74 +/- 0.36 and 2.64 +/- 0.77 after slow inhalation (p less than 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740582 TI - Quantitative IgE- and IgG-subclass responses during and after long-term ragweed immunotherapy. AB - We studied the quantitative responses of short ragweed (RW)-pollen-specific serum antibodies in 22 patients with RW immunotherapy (IT) and in a different set of 31 patients, 16 of whom stopped RW IT after more than 5 years of treatment. Serum was assayed before and after season, 1 year before and 1 and 2 years after starting IT, and 1 year and 2 years after stopping IT. RW pan-IgG, RW IgG1, and RW IgG4 were measured by ELISA, and RW IgE by RAST. Absolute quantities of RW IgG1 and RW IgG4 in reference sera were estimated by least-squares multiple regression analysis of 223 sera with the equation RW pan-IgG = RW IgG1 + RW IgG4. IgG1 is dominant in the early immune response of IT and disappears relatively slowly when IT is stopped. In contrast, IgG4 appears in significant quantities only after prolonged IT and disappears rapidly when IT is stopped. The apparent average half-life of RW IgG4 (9 months) was significantly shorter than that of RW IgG1 (29 months) (p less than 0.001). Before IT, mean RW IgE rose 180% (p less than 0.01) during the RW pollination season (August to November). This seasonal rise in RW IgE was ablated after IT from 1 year up to 8 years, but returned the year after IT was stopped. After 2 years of IT, the RW IgG1 and IgG4 levels were significantly correlated with RW IgE (r = 0.94 and 0.81; p = 0.0001 and 0.005). PMID- 1740583 TI - Immunotherapy with honeybee venom and yellow jacket venom is different regarding efficacy and safety. AB - Venom immunotherapy (VIT) for Hymenoptera allergy is accepted as safe and effective. However, widely varying success rates and frequencies of side effects are reported. Differences between various Hymenoptera species could account for these diverging results. We therefore analyzed 205 patients with a history of systemic allergic reactions to either honeybee (148 patients) or yellow jacket stings (57 patients) during VIT. All patients had a positive skin test to the respective venom before VIT, were monitored for side effects of VIT, and submitted to a sting challenge while they were receiving VIT. Patients with honeybee-venom allergy had a higher sensitivity in both skin tests (p less than 0.05) and RAST (p less than 0.001) than patients with yellow jacket-venom allergy. They developed systemic side effects to VIT injections significantly more often (41% versus 25%; p less than 0.01) and also reacted more frequently to the sting challenge (23% versus 9%; p less than 0.01) than patients with yellow jacket-venom allergy. We conclude that results obtained from studies on the allergy to one Hymenoptera venom cannot be extrapolated to allergies to other Hymenoptera venoms. PMID- 1740584 TI - Benzyl benzoate moist powder: investigation of acaricidal [correction of acarical] activity in cultures and reduction of dust mite allergens in carpets. AB - Despite advances in the understanding of dust mites, it remains difficult to control exposure to mite allergens, and it is particularly difficult to reduce mites in fitted carpets or sofas. Several chemicals have been demonstrated to kill mites or denature mite allergens, and some of these chemicals have been investigated in carpets. Benzyl benzoate (BB), which has been widely used to kill scabies mites and is known to kill mites of the genus Dermatophagoides, has been used as a method of treating carpets. The present article describes experiments in the laboratory and in houses in testing two preparations of BB, a moist powder and a foam. The moist powder is composed of two ingredients, a wetted "inert" cellulose, which is designed to act as a cleaning agent, and the active BB adsorbed onto silicates. The active powder kills 90% of mites in culture within 12 hours and 100% in 24 hours, whereas the cellulose is not acaricidal. The moist powder preparation was highly effective at killing D. farinae and D. pteronyssinus mites in the laboratory. In carpets the moist powder, applied for 12 hours with repeated brushing, was demonstrated to reduce the concentrations of group I and group II dust mite allergens in dust recovered at 1 month. This decrease in concentration could, in part, be explained by a persistent increased recovery of dust caused by residual white powder. However, when the recovery of group II allergens was calculated as the total allergen recovered, the decrease was highly significant at 2 weeks and 4 weeks after treatment (p less than 0.001). Application of the powder to carpets for 4 hours or of the foam to sofas was less effective. After 2 months the effect on mite antigen in carpets was still present, but some increase was apparent, suggesting that repeat application after 2 or 3 months would be necessary to control mite-allergen levels. PMID- 1740585 TI - Activation of the coagulation pathway during ongoing allergic cutaneous reactions in humans. AB - The levels of histamine, fibrinopeptide A (FPA), and IgG were determined in chamber fluids overlying sites of antigen versus buffer incubation for up to 7 hours in seven atopic and four antigen-nonreactive subjects. Significant increases in histamine were observed at antigen versus buffer sites in the atopic subjects throughout the 7-hour period. FPA and IgG levels were higher in antigen than in buffer sites from 0 to 5 hours in the atopic subjects. Furthermore, FPA levels correlated with the magnitude of induration at 6 hours after antigen injection in atopic subjects. There were no differences in the levels of histamine, FPA, or IgG at antigen versus buffer sites in the skin test-negative subjects. We suggest that the combination of vascular leakage of proteins, induced by vasoactive mediator release, and activation of these proteins during ongoing cutaneous reactions is responsible for fibrin formation that contributes to the pathophysiology of late-phase allergic responses in the skin. PMID- 1740586 TI - Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity. AB - Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS. PMID- 1740587 TI - Comparison of human nasal mucosal secretion in vivo and in vitro. AB - The secretion of proteins from the human nasal mucosa induced by histamine, alpha adrenergic, beta-adrenergic, and cholinergic agonists was studied in vivo and in vitro. Glandular secretion of lactoferrin, lysozyme (in vivo only), and respiratory glycoconjugates (RGCs) was measured. Vascular permeability was determined in vivo by albumin secretion in relationship to the other proteins. Muscarinic stimulation by methacholine induced significant glandular secretion (lactoferrin, lysozyme and/or RCGs) both in vivo and in vitro, confirming that muscarinic receptors are stimulated directly. Histamine induced predominantly vascular permeability in vivo but caused some glandular secretion as well. However, in vitro, histamine had no effect on glandular secretion, suggesting that histamine acts predominantly on the nasal vascular bed and only affects glandular secretion through reflex actions. Phenylephrine, an alpha-adrenergic agonist, selectively stimulated lysozyme release in vivo, and both RGCs and lactoferrin release in vitro. Thus, alpha-adrenergic stimulation has some direct, albeit minimal, capacity to stimulate mucosal glands. beta-Adrenergic agonists had no effect on glandular secretion or vascular permeability either in vivo or in vitro. Therefore, glandular secretion is directly stimulated by alpha adrenergic and cholinergic agonists, but not by beta-adrenergic agonists. The stimulation of glandular secretion by histamine is indirect and mediated through the action of neural reflexes. PMID- 1740588 TI - HLA-DR4-associated nonresponsiveness to mountain-cedar allergen. AB - We did human lymphocyte antigen (HLA)-DR and DQ typing on 37 subjects with mountain-cedar (MC) pollinosis as defined by history and a positive skin test. Of these 37 subjects, 31 were subdivided into 18 subjects with a single positive skin test (SPST) and 13 subjects with multiple positive skin tests (MPSTs). We also typed 51 subjects without MC sensitivity or atopy as defined by history and negative skin tests to a battery of aeroallergens. We also typed 116 subjects in whom MC sensitivity had not been determined. Total IgE, Mc-specific immunoglobulin E (sIgE), and MC-sIgE binding bands by immunoblot were also determined on the subjects with SPSTs and MPSTs. No significant differences were found between the subjects with SPSTs and MPSTs for HLA type, total IgE, MC sIgE, or bands bound by MC sIgE by immunoblot. There was a strong negative relationship between HLA-DR4 and subjects with MC pollinosis; chi-square, 14.857; p = 0.0096; and odds ratio, 0.139. These findings suggest that there is no difference in genetic immunoregulation between subjects with SPSTs and MPSTs but that the presence of the DR4 gene product is associated with a decreased risk of an IgE response to MC and protection from MC pollenosis. PMID- 1740589 TI - Changes in bronchial responsiveness following nasal provocation with allergen. AB - The relationship between upper airway inflammation and asthma is controversial. In the current study, we sought to investigate the relationship between allergic rhinitis and lower airway dysfunction by performing double-blind, randomized nasal challenges with allergen or placebo. Subjects were selected for a prior history of asthma exacerbations after the onset of seasonal allergic rhinitis symptoms. After the induction of a marked nasal-allergic reaction (with a technique of nasal provocation that limited allergen delivery to the nose), there were no changes in FEV1, specific conductance, or lung volumes either 30 minutes or 4 1/2 hours after nasal allergen challenge, nor any changes in peak flow rates followed hourly until the next day. However, nasal provocation with allergen resulted in a relative increase in bronchial responsiveness to methacholine compared with that to placebo (p = 0.011 at 30 minutes and p = 0.0009 at 4 1/2 hours after challenge). Our study suggests that, although a nasal-allergic response does not induce airflow limitation of the lower airways, it can alter bronchial responsiveness. PMID- 1740590 TI - Is there a role for cyclosporine in asthma? PMID- 1740591 TI - Suffocating odor and asthma after Acarosan-powder carpet treatment. PMID- 1740592 TI - Evidence of mast cell involvement in a clinical syndrome mimicking toxic shock syndrome. PMID- 1740593 TI - Ambulatory monitoring of sleep-wakefulness patterns in healthy elderly males and females (greater than 88 years): the "Senieur" protocol. AB - OBJECTIVE: The study was designed to investigate sleep-wake patterns in healthy elderly men and women (greater than 88 years) using ambulatory recording techniques. DESIGN: Cross-sectional observations on 2 consecutive days. METHODS: Two consecutive 24-hour recordings were made. Each 30-second period of the recording was scored as characteristic of wakefulness, REM, and non-REM sleep (stages 1-4). SETTING: Interviews and recordings were done in the home of the elderly, not interfering with the habitual routine. PARTICIPANTS: Among eligible members of the "Senieur" protocol, screened for wellness, seven females (88-102 years) and seven males (88-98 years) volunteered to participate. MAIN OUTCOME MEASURES: Organization of sleep, sleep structure, and daytime mapping. RESULTS: There was no difference between the first and second night recording. Important gender differences were observed: males had significantly less total sleep, shorter REM latency, more transitions to wake from REM, less NREM 3 sleep, and virtually no NREM 4. Daytime napping, REM amount, and distribution did not show sex differences. Although the variability in the amount of napping was considerable, it occupied less than 10 percent of the total sleep time in both women and men. Daytime napping was unrelated to sleep characteristics. CONCLUSIONS: Ambulatory sleep-wake recordings allow an objective and critical evaluation of sleep function in normal aging. Interesting findings include a shift of REM sleep to the first part of the sleep period an increased cycle variability, and non-correlation of night-time sleep with daytime napping. In contrast to earlier findings in elderly persons, a polygraphic and subjective first-night effect was lacking. PMID- 1740594 TI - Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings. AB - OBJECTIVE: To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season. DESIGN: Prospective descriptive study, without intervention. METHOD: Patients with respiratory illnesses were evaluated by a directed history and physical examination. Nasopharyngeal secretions for viral culture were obtained, and acute and convalescent serum samples were obtained for analysis. Serologic evidence of infection with respiratory syncytial virus (RSV) and parainfluenza were determined by enzyme immunoassay (EIA), and influenza by hemagglutination inhibition assay and EIA. SETTING: A 591-bed nursing home. PARTICIPANTS: Residents with signs or symptoms of acute respiratory illness (nasal congestion, pharyngitis, cough, wheezing, or respiratory difficulty) were eligible for study. RESULTS: A viral etiology was documented in 62 out of 149 illnesses (42%). RSV was the most common virus associated with illness; it was documented in 27% of respiratory illnesses, followed by rhinovirus (9%), parainfluenza (6%), and influenza (1%). RSV was associated with significantly more severe disease when compared with rhinovirus. Clustering of specific viral infections occurred, suggesting nosocomial transmission. CONCLUSIONS: Viruses are an important cause of acute respiratory infections in the institutionalized elderly during the winter months. PMID- 1740595 TI - Positron emission tomography and familial Alzheimer's disease: a pilot study. AB - OBJECTIVE: Local cerebral metabolic rates for glucose were compared between patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's Disease (SAD), and normal controls (NC) to determine if FAD is associated with a unique pattern of brain metabolism. DESIGN: Case-control study matched to convenience sample of FAD. METHODS: Subjects in the three diagnostic groups were scanned using fluorodeoxyglucose and the Positron Emission Tomographic (PET) technique. The criterion standard of a detailed clinical history and examination were compared to scan results. SETTING: Patients in a university hospital. SUBJECTS: Ambulatory controls and Alzheimer's patients, both sporadic (n = 8) and familial (n = 7). The two groups were similar in severity of cognitive dysfunction. RESULTS: FAD and SAD patients did not significantly differ in terms of local cerebral metabolic rates for glucose. PMID- 1740596 TI - Hearing loss prevalence and management in nursing home residents. AB - OBJECTIVES: To determine the prevalence and management of hearing loss and hearing handicap among non-demented nursing home residents. DESIGN: Descriptive study of total population of two nursing homes. PARTICIPANTS: All 121 eligible residents. SETTINGS: Two nursing homes. MINI OUTCOME MEASURES: Audiometry, questionnaires of nurses and subjects regarding perceived hearing handicap, and documentation in medical records of hearing loss. RESULTS: 77% had at least a mild (greater than or equal to 26 dB Hearing Level) hearing loss in the better ear, and 51% had a moderate to severe loss (greater than or equal to 41 dB HL). Self-assessments of hearing handicap by residents, together with audiometric findings and expressed interest in a hearing aid, were more useful guides for aural rehabilitation needs than were nurses' assessments of residents' handicaps. Medical records failed to identify 48% of residents with moderate to severe hearing losses. Fifty-eight percent of residents with severe hearing loss currently had hearing aids, and 38% more would like to have an aid. CONCLUSIONS: Residents should have hearing evaluations with documentation of results on admission and periodically under the direction of a nurse trained as a hearing specialist. Environmental modifications of the NH plus use of hearing aids can improve hearing. PMID- 1740597 TI - The effects of patterned urge-response toileting (PURT) on urinary incontinence among nursing home residents. AB - OBJECTIVE: To test an individualized form of habit training for urinary incontinence (UI) among long-stay cognitively and/or physically impaired elderly nursing home residents over time. DESIGN: Randomization of subjects occurred by nursing home unit. Baseline wet checks were done hourly for one 24-hour period at 3-week intervals over 12 weeks followed by 72 hours of continuous electronic monitoring to establish precise voiding patterns for each subject. The 12-week intervention period was administered by indigenous staff after they attended a 4 hour UI educational program. Subjects were followed an additional 12 weeks to determine the extent of maintenance of the intervention among staff and subjects. SETTING: Four non-profit nursing homes; west, mid-west, east coast. PATIENTS: Consent was obtained from 154 (71%) who met primary inclusion criteria. Forty-one failed the secondary inclusion criteria leaving 113 who entered the 37-week study. Eighty-eight completed the study (experimental = 51, control = 37); all were physically and/or mentally impaired, averaged age 85, and had either urge or urge/stress UI. RESULTS: UI was significantly decreased during the 3-month period (P less than 0.001). Eighty-six percent showed improvement over baseline while one-third improved 25% or more over their baseline UI rate. The control group's UI increased during the same period of time. The volume of UI among the experimental group also decreased (P less than 0.005) while the control group's UI volume increased. CONCLUSIONS: The training program was effective in reducing UI though compliance among nursing staff averaged only 70% of the prescribed toileting times. The success of this approach is similar to other recently described behavioral programs but achieved the reduction using only regular nursing staff. This individualized approach supports the recent regulatory thrust to individualize care to promote and maintain functional abilities and autonomy. PMID- 1740598 TI - The impact of pacemaker implantation on cognitive functioning in elderly patients. AB - OBJECTIVE: To describe and quantify the impact of pacemaker implantation on cognitive functioning in the elderly. DESIGN: Prospective case-control, non randomized trial. Data were collected from clinical and family interviews and from a psychological test battery. SETTING: Pacemaker clinic in a tertiary care hospital. PARTICIPANTS: Nineteen elderly (65+ years) patients undergoing new or replacement pacemaker implantation for dysrhythmias and volunteer controls matched for age, sex, and short Mental Status Questionnaire test results, without dysrhythmia or intervention. MAIN OUTCOME MEASURES: Subjective and clinical impressions based on family interviews; results of psychological test battery before and 6-12 months after pacemaker implantation. RESULTS: Prior to pacemaker implantation, three patients met DSM-III criteria for dementia and two for delirium. Paced patients demonstrated deficiency in immediate memory, language, memory for less structured information, and learning of abstract materials. These deficits were due primarily to the poor performance of patients with complete heart block. Despite clinical and subjective impressions of improvement, there was no change in psychologic test performance subsequent to pacemaker implantation. CONCLUSIONS: Impaired cognitive functioning is not always clinically apparent but appears common in patients with cardiac dysrhythmias; it is not altered 6-12 months after pacemaker implantation. PMID- 1740599 TI - Diabetes support groups improve health care of older diabetic patients. AB - OBJECTIVE: To assess whether knowledge or psychosocial and glycemic benefits of a diabetes education program are enhanced by a support group for older patients. DESIGN: A partially randomized controlled trial involving two groups of patients: Group A, subjects who received an education program followed by 18 months of support group sessions; Group B, only the diabetes education program. A third convenience sample, Group C, received neither intervention. Groups A and B were assessed before and immediately after the education program, and all groups were assessed 2 years after the education program. SETTING: Diabetes clinic at a Veterans Affairs Medical Center. PATIENTS: All subjects were male (mean age = 68 +/- 1.3 years, range = 57-82 years; duration of diabetes = 10 +/- 2 years, range 3-16). Sample sizes were 11 in Group A, 13 in Group B, and 8 in Group C. INTERVENTION: The education program consisted of six weekly sessions covering aspects of diabetes self-care. The support group consisted of 18 monthly sessions for continuing education, discussion, and structured social activities. OUTCOME MEASURES: Diabetes knowledge, psychosocial factors (self-care-related quality of life, stress, family involvement in care, and social involvement), depression, and glycemic control. RESULTS: Group A scored better (at least P less than 0.05) on knowledge, quality of life, and depression than the other groups. Groups A and B showed less stress, greater family involvement, better glycemic control, but less involvement in social activities than Group C. CONCLUSION: Diabetes education programs can have long term benefits on knowledge, psychosocial functioning, and glycemic control for older diabetic patients. The addition of support groups enhances diabetes knowledge and psychosocial functioning. PMID- 1740600 TI - Body composition in elderly men: effect of dietary modification during strength training. AB - OBJECTIVE: To assess how dietary change affects gain in strength and muscle mass during heavy resistance training of elderly men. DESIGN: Randomized controlled trial. INTERVENTION: During 12 weeks of resistance training of knee extensors and flexors, a daily supplement of 560 +/- 16 kcal/day (17% energy from protein, 43% from carbohydrate, 40% from fat) was randomly assigned to six men (S) while five men (U) received no supplement. Food intake, strength, whole body composition, and midthigh composition by CT scan were assessed before training and at 6 and 12 weeks. SETTING: The men were outpatients but lived in a Metabolic Research Unit during the three assessments. PARTICIPANTS: Eleven healthy men aged 61 to 72 years. RESULTS: Densitometry showed no change over time in fat or fat-free mass. However, the S men increased (P less than 0.05) weight, skinfold thickness at six sites, subcutaneous midthigh fat, and creatinine excretion; in all men, changes in these values and in midthigh muscle were proportional to changes in reported energy intake (P less than 0.05). There was midthigh muscle hypertrophy in both groups, but it was greater in S than U (P less than 0.01). Both groups gained strength (P less than 0.001) with no effect of diet. CONCLUSIONS: During physical rehabilitation of the elderly, dietary intake may influence the increase in lean as well as adipose tissue without altering strength gain. These preliminary findings should be confirmed by a larger study with sedentary controls. PMID- 1740601 TI - Reduced infectivity of cold-adapted influenza A H1N1 viruses in the elderly: correlation with serum and local antibodies. AB - OBJECTIVE: To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus. DESIGN: Time series, comparing outcomes in young and elderly convenience sample. METHOD: Retrospective laboratory analysis of serum and nasal wash specimens collected during prior studies in which young or elderly volunteers had been inoculated with cold-adapted influenza A/Kawasaki/86 (H1N1) reassortant virus. SETTING: Johns Hopkins Center for Immunization Research. PARTICIPANTS: Healthy young and elderly adults with pre-vaccination serum hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8. OUTCOME MEASUREMENTS: Antibody responses in serum and nasal washes. MAIN RESULTS: The proportion of vaccinees who developed any serum or local antibody response was higher in young compared with elderly subjects (20/20 vs 5/14, P less than 0.0005). Resistance to infection with cold-adapted virus correlated with pre vaccination levels of serum immunoglobulin G (IgG), serum IgA, and nasal wash IgA antibody to whole virus antigen. Age was highly correlated with a lack of response to vaccine by simple regression, but not when data were adjusted for pre existing antibody levels. CONCLUSIONS: Cold-adapted reassortant influenza A H1N1 viruses achieve lower rates of infection in elderly than young adults, primarily due to age-related differences in preexisting levels of immunity which may not be reflected by HAI titer. PMID- 1740602 TI - Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. AB - OBJECTIVE: To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction. DESIGN: Time series data collected in an open trial of parenteral cobalamin therapy. SETTINGS: Outpatient geriatric assessment centers, inpatient geropsychiatry unit, and tertiary care university hospital. PARTICIPANTS: Twenty-two subjects with low serum cobalamin (less than 150 pmol/L) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time. Eighteen subjects completed the study. INTERVENTIONS: Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week, then weekly for 1 month, then monthly thereafter for a minimum of six months. OUTPATIENT MEASURE: The Mattis Dementia Rating Scale (DRS) was administered both before and at least 6 months after full cobalamin replacement therapy. The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori. RESULTS: After a minimum of 6 months of cobalamin therapy, 11 of 18 patients showed cognitive improvement. There was a striking correlation between duration of cognitive symptoms and response to therapy. Patients symptomatic for less than 12 months gained an average of twenty points on the DRS (paired t test P = 0.0076), whereas patients symptomatic greater than 12 months lost an average of three points (paired t test P = .34). Two patients symptomatic for only 3 months normalized their DRS scores, gaining 31 and 28 points, respectively. CONCLUSION: There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin. PMID- 1740603 TI - Study of strategies for the recruitment of elders including the use of community volunteers. AB - OBJECTIVES: The primary objective was to compare study participation when first contact was made by telephone versus an unscheduled visit to the household. The secondary objective was to compare study participation when three differing modes of questionnaire presentation were used. DESIGN: The residents of 300 randomly selected households were contacted by community volunteers and asked to participate in a study of the etiology of cancer and other chronic diseases. Two methods of first contact were used, a telephone call to schedule a home visit and an unscheduled visit to the household. Three modes of questionnaire presentation were used. PARTICIPANTS: Residents of a retirement community in Arizona who were aged 50 or over. MAIN OUTCOME MEASURES: Agreement to participate, defined as acceptance of and agreement to complete the study questionnaires. Participation in the study, defined as acceptance and completion of the study questionnaires. RESULTS: No difference was observed in participation when first contact was made by telephone (46%) as compared with an unscheduled visit to the household (45%) (P = 0.83). Similarly, no difference in the participation was observed between three modes of presentation of the questionnaire to the householders (P = 0.13). Agreement to participate was, however, significantly higher when first contact was made by visiting the home (81% vs 55%) (P less than 0.001). CONCLUSIONS: Neither the strategy used for first contact nor mode of questionnaire presentation affected participation. PMID- 1740604 TI - Tuberculosis in aging adults. PMID- 1740605 TI - Advances in Alzheimer's disease. PMID- 1740606 TI - Oral cancer: to screen or not to screen? PMID- 1740607 TI - Effects of strength training in elderly women. PMID- 1740608 TI - Alarm devices instead of restraints? PMID- 1740609 TI - The clinical importance of environmental lighting to the elderly. AB - 1. Nurses need to be aware of the effects of artificial lights on the aged because the aged spend a greater amount of time under these lights than do younger people. 2. Although the aged require more light than younger people to see, bright lights may cause glare. The use of indirect lighting is recommended to reduce problems with glare. 3. The aged see best under artificial lighting that simulates natural sunlight. 4. Nurses who work in institutional settings should be sensitive to the need for individualized light-dark cycles. PMID- 1740610 TI - Education in the elderly. Adapting and evaluating teaching tools. AB - 1. The patient's Bill of Rights documents the rights of patients to be informed of their illness, health, and treatment. 2. The use of appropriate teaching tools can significantly increase learning, especially if the tools are modified to accommodate normal aging changes. 3. An appropriate teaching tool is a critical component to the learning success of the elderly. 4. With aging changes that result in loss of short-term memory, a teaching tool may make the difference between short-term learning and long-term success. PMID- 1740611 TI - Releasing restraints in the nursing home: it can be done. AB - 1. The value of physical restraints for nursing home residents has not been documented, yet they have been used almost universally for at least 50 years. 2. The use of physical restraints for confused patients produces numerous negative outcomes. 3. Nursing homes can create environments that are restraint-free for all residents, and demonstration trials have proven the feasibility of restraint free care. 4. A restraint-free environment produces a dramatic decrease in agitation and mobility problems. PMID- 1740612 TI - The relationship of anxiety to development of postoperative delirium. AB - 1. Although patients who experience unplanned, unanticipated surgery were not more anxiety prone than patients undergoing planned surgery, they did experience higher levels of state anxiety and a higher incidence of delirium postoperatively. 2. Nurses should be alert to an increased risk of negative outcomes among patients with little or no opportunity for psychological preparation prior to surgery, and especially among patients undergoing unanticipated orthopedic surgery. 3. State anxiety scores among patients undergoing unplanned surgery declined postoperatively rather than rose. This indicates that the critical period for nursing intervention may be in the preoperative period. 4. Delirium is not associated with anxiety in a direct or linear way. Patients who experience delirium postoperatively do not experience greater state anxiety, nor are they more anxiety prone than patients who do not exhibit delirium. PMID- 1740613 TI - The music therapy assessment tool in Alzheimer's patients. AB - 1. Empirical research is needed to evaluate immediate and sustained physiological, psychological, and psychosocial therapeutic effects, if any, of music therapy on behavioral patterns of elderly institutionalized Alzheimer's patients. 2. The Music Therapy Assessment Tool (MTAT) was specifically designed and developed to assess the effects of music therapy on behavioral patterns of Alzheimer's disease patients. 3. Preliminary testing of the MTAT suggests that it has fairly high internal consistency and inter-rater reliability and warrants consideration as a research tool. 4. Musical intervention included familiar music to facilitate communication and socialization, ethnic and nostalgic music to stimulate reminiscence, and melodies with distinctive rhythmic patterns to enhance movement and behavioral repatterning. PMID- 1740614 TI - Implementation of a urinary continence program. AB - 1. Meaningful involvement of staff supports the tenet that staff must not only participate in making decisions that they perceive as being important to them, but that they also perceive that their participation has an impact. 2. Urinary incontinence accompanies dementia of the Alzheimer's type because the person forgets how to locate the bathroom, is unable to communicate the need to void, and has an impaired central inhibition of elimination. Regular toileting schedules help promote continence. 3. Strategies that encourage staff participation in a new program include the deliberate use of wording, anonymous written input on select forms, and ongoing support and recognition. Staff members must feel respected for their knowledge, ideas, and experience. PMID- 1740615 TI - The challenge of caring: behavioral management. PMID- 1740616 TI - Blood shortage. PMID- 1740617 TI - Health policy commission sees no easy answers. Interview by Bob Carlson. PMID- 1740618 TI - New Medicare formula: RVU x GAF x CF = ? PMID- 1740620 TI - ISMA lobbying team plays offense, defense. PMID- 1740619 TI - Gallup Poll reflects Indiana attitudes on health care. PMID- 1740621 TI - New alternatives in gallstone treatment. AB - Within the past few years, a number of new treatment modalities for gallbladder stones have become available. Laparoscopic cholecystectomy has proved as safe as traditional surgical cholecystectomy, without the discomfort and lengthy recuperation associated with a large abdominal incision. Several other new treatments also have been investigated, including percutaneous cholecystolithotomy, peroral drug chemolysis, extracorporeal shock wave lithotripsy, and methyl-tert-butyl ether lavage. The relative merits and disadvantages of these treatments, compared to each other and to standard cholecystectomy, are described herein. PMID- 1740622 TI - Echoes in the halls: thoughts on double publication. PMID- 1740623 TI - What molecular biology has taught us about fibrinolysis. PMID- 1740624 TI - Fibrinogen deposition and macrophage-associated fibrin formation in malignant and nonmalignant lymphoid tissue. AB - Nonmalignant lymphoid tissue and tissue from patients with nodular sclerosis, Hodgkin's disease, and large cell lymphocytic lymphoma was examined by immunohistochemical techniques for the occurrence in situ of components of coagulation and fibrinolysis reaction pathways. Staining for material interpreted as fibrinogen was observed in abundance in both malignant and reactive lymphoid tissue. Fibrin also occurred to a variable extent but focally in all tissues. Components of coagulation pathways, including tissue factor, factor VII, factor X, and factor XIII ("a" subunit), were restricted to tissue macrophages. Double labeling techniques revealed fibrin in direct apposition to tissue macrophages. We conclude that fibrinogen and fibrin occur in both benign and malignant lymphoid tissue and that the transformation of fibrinogen to fibrin is attributable to macrophage-initiated thrombin formation. We postulate that both systemic and local hypercoagulability associated with these disorders may be attributable to macrophage activation resulting in expression of procoagulant activity. PMID- 1740625 TI - Fibrin coating of bladder tumor cells (T24) is not protective against LAK cell cytotoxicity. AB - Certain evidence indicates that tumor cells in the circulation may be enshrouded with a coat of fibrin. It has been suggested that this fibrin coat protects tumor cells from attack by the immune system. This study compared the interaction of lymphokine activated killer (LAK) cells with tumor cells alone and with fibrin coating. LAK cell killing of cultured human bladder tumor cells (T24) was measured by a 4-hour chromium release assay. Tumor cells (3 x 10(6] were incubated with Na51CrO4 for 2 hours at 37 degrees C and 5% CO2 in serum-free medium. After washing, one half of the cells were coated with fibrin by exposure to recalcified platelet-poor plasma. Fibrin coating was confirmed by immunofluorescence with anti-human-fibrinogen-fluorescein-conjugated antibodies. LAK cells were prepared from peripheral blood lymphocytes by incubation with interleukin-2 at a concentration of 1000 units of interleukin-2/1 ml serum-free medium/1 million cells for 5 days at 37 degrees C, 5% CO2. Five thousand tumor cells with or without fibrin were incubated with varying concentrations of either LAK or peripheral blood lymphocytes (10,000 to 100,000 cells). After 4 hours the supernatants were harvested and counted in a gamma counter for 1 minute. Over a range of effector-to-target cell ratios of 10:1 to 100:1 (LAK to T24), no difference was seen in percentage of specific lysis for T24 alone versus fibrin coated T24 cells. At a ratio of 100:1 (LAK to T24), percentage of specific lysis was 83.3% versus 87.7% for uncoated and coated T24 cells, respectively. This suggests that fibrin coating of tumor cells is insufficient to provide protection from LAK cell killing. PMID- 1740626 TI - Stimulation of growth of neuroblastoma cells by ferritin in vitro. AB - Among children with advanced neuroblastoma, serum concentrations of the iron storage protein ferritin correlate inversely with prognosis. To determine whether ferritin stimulates tumor cell growth, the effects of graded concentrations on cell number were studied for each of three neuroblastoma cell lines (CHP-126, CHP 100, IMR-32) plated in serum-free tissue culture medium. Ferritin extracted from human liver, spleen, or CHP-126 cells (150 ng/ml, final concentration) but not from human heart (150-300 ng/ml) resulted in 1.4-fold +/- 0.2-fold increases in cell numbers over 72 hours as measured spectrophotometrically after reduction of a tetrazolium dye. Higher concentrations of isoferritins (up to 1000 ng/ml) did not further increase cell number, but stimulation was abrogated by rabbit immunoglobulin G antiferritin. Although specific receptors for iodine 125-labeled ferritin could not be demonstrated on the two cell lines tested, deoxyribonucleic acid (DNA) synthesis, measured by incorporation of 3H-thymidine, also increased after addition of ferritin, by approximately 25%. We conclude that ferritin has mitogenic activity for human neuroblastoma cells in vitro which may explain the clinical correlation between levels of that protein and prognosis. Possible implications for therapy are discussed. PMID- 1740627 TI - Improved maintenance of platelet in vivo viability during storage when using a synthetic medium with inhibitors. AB - We report on the storage of platelet concentrates and the effects on in vivo and in vitro platelet function tests of adding the platelet inhibitors prostaglandin E1 and theophylline to a plasma-free synthetic medium and storage in containers with reduced surface-to-volume ratio. Paired in vivo studies on platelets labeled with indium 111 after 14-day storage demonstrated higher recoveries (mean +/- SD) of 23% +/- 9% and longer survivals of 109 +/- 59 hours for the test group versus 8% +/- 10% and 19 +/- 22 hours, respectively (p less than 0.01), for the control group (synthetic medium with no inhibitors and use of standard containers). The improved viability was associated with a significantly lower glycolytic rate; better maintenance of other in vitro parameters including respiratory activity, adenosine triphosphate levels, hypotonic shock response, surface glycoprotein Ib (by flow cytometry); and improved preservation of morphologic integrity (p less than 0.05). In particular, a strong inverse correlation (r = -0.91) was observed between in vivo recoveries and the fraction of platelets negative for glycoprotein Ib. We conclude that avoidance of platelet activation by a combination of inhibitors, plasma removal, and reduced container surface improves platelet respiratory activity, adenosine triphosphate and glycoprotein Ib levels, and posttransfusion viability of platelet concentrates stored for 14 days. PMID- 1740628 TI - Modification of platelet and lymphocyte calcium handling and blood pressure by dietary sodium and calcium in genetically hypertensive rats. AB - Abnormal cellular calcium handling has been postulated to be involved in the pathogenesis of hypertension. To determine whether the blood pressure response to dietary manipulation of sodium level (as the chloride salt) and calcium level is associated with changes in cellular cation metabolism, the interactive effects of both dietary components on blood pressure and intracellular free calcium concentration [( Ca2+]i) in blood platelets and thymic lymphocytes, erythrocyte sodium content, and blood ionized calcium were examined in stroke-prone spontaneously hypertensive rats. Rats were fed low (0.3%) or high (3.1%) sodium and low (0.2%) or high (2.0%) calcium diet for 6 weeks. With the rats receiving the high sodium-low calcium diet, systolic blood pressure was higher than with other diets, among which no difference was detected. Both basal [Ca2+]i and ionomycin (50 and 150 nmol/L) stimulated [Ca2+]i in platelets, and in lymphocytes, were higher with the high sodium-low calcium diet than with the others. Thus the high sodium diet elevated blood pressure and increased [Ca2+]i in the resting and stimulated state in both cell lines with the low-calcium but not the high-calcium diet. The high-sodium diet was associated with increased sodium content of erythrocytes, whereas manipulations of dietary calcium level had no effect on erythrocyte sodium content. Dietary calcium level had more of an effect on blood ionized calcium than did dietary sodium level. In combined diet groups, blood pressure was positively, significantly correlated with basal and ionomycin-induced [Ca2+]i in platelets (r = 0.64 and 0.67, respectively) and in lymphocytes (r = 0.53 and 0.60, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740629 TI - Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. AB - Increased vasopermeability and vasodilation, presumably the result of endothelial perturbation, are considered among the basic pathogenetic mechanisms in septic shock. Neutrophils have been implicated as a source for mediators in endothelial injury. We measured elastase-alpha 1-antitrypsin (alpha 1AT) complexes and lactoferrin as markers for release of neutrophil granule contents in plasma from patients with sepsis on admission to the Intensive Care Unit, and we delineated the relationship of neutrophil activation to other inflammatory parameters and to hemodynamic and biochemical parameters. Levels of elastase-alpha 1AT and lactoferrin significantly correlated with each other (r = 0.58; p less than 0.008), and were increased (greater than 3.33 and 5 nmol/L, respectively) in 96% and 71% of the patients, respectively. Lactoferrin, but not elastase-alpha 1AT, correlated with the number of white blood cells (r = 0.38; p = 0.008). Elastase alpha 1 AT levels were significantly higher (p = 0.008), whereas white blood cell counts were lower (p = 0.015) in patients with shock when compared with patients without abnormal blood pressure. Both elastase-alpha 1AT and lactoferrin levels correlated with lactate levels (r = 0.33; p = 0.024 and r = 0.30; p = 0.04), suggesting a role for neutrophil activation in the pathogenesis of hypoxygenation. In addition, elastase-alpha 1AT correlated with the concentrations of interleukin 6 (IL-6) (r = 0.46; p = 0.001) and C3a (r = 0.38; p = 0.009), suggesting that cytokines and complement may contribute to the degranulation of neutrophils in sepsis. Elastase-alpha 1AT complexes were inversely related to C1-inhibitor (r = -0.33; p = 0.028) and to platelet numbers (r = -0.42; p = 0.003). Levels of elastase-alpha 1AT complexes in plasma appeared to be of prognostic significance; levels were higher in 27 patients who died than in 21 patients who survived (p = 0.01). The mortality in 27 patients with concentrations below 10 nM was 37%, whereas it was 81% in 21 patients with higher levels. The overall mortality in this study was 56%. These results provide further evidence that activation and degranulation of neutrophils, induced by multiple agonists, are involved in the development of fatal complications in patients with sepsis. PMID- 1740630 TI - Degradation of rat lung collagens by cathepsin B. AB - The lysosomal proteinase cathepsin B degrades purified insoluble collagen in vitro. To determine whether the enzyme degrades collagens present in normal extracellular matrices, we quantitated release of hydroxyproline-containing peptides during incubation of rat lung explants with bovine spleen cathepsin B. Incubation of explants with cathepsin B at pH 5.9 caused significant release of hydroxyproline, indicating collagen degradation, without apparent injury to lung parenchymal cells, as determined by release of lactate dehydrogenase. Release of hydroxyproline was completely inhibited by E-64, a specific inhibitor of cysteine proteinases. Cathepsin B demonstrated significant collagenolytic activity over a range of pH values from 4.0 to 6.5. Little activity was present at pH 7.0 or above. The findings indicate that cathepsin B is capable of degrading collagens embedded in the complex extracellular matrix of the lung and suggest that the enzyme may contribute to collagen degradation in vivo. PMID- 1740631 TI - Effects of extraerythrocytic hemoglobin and its components on mononuclear cell procoagulant activity. AB - Earlier studies performed in rabbits in this laboratory showed that human hemoglobin causes leukocyte infiltration into heart and lung tissues and coagulation abnormalities including thrombosis. Since stimulation of peripheral blood mononuclear cells induces procoagulant activity, we investigated the possibility that isolated peripheral blood mononuclear cells from humans and rabbits were stimulated by hemoglobin to produce a procoagulant activity response. Stroma-free hemoglobin and its purified components were assayed for their stimulatory effect on peripheral blood mononuclear cells. The added effect of endotoxin contamination was also explored. A significant dose-dependent effect of stroma-free hemoglobin on procoagulant activity was found with both human and rabbit peripheral blood mononuclear cells, but rabbit cells were found to be 50 fold more sensitive than human cells. Hematin, methemoglobin, and purified hemoglobin Ao elicited procoagulant activity effects with human peripheral blood mononuclear cells, but isolated globin did not. We also studied the effects of these compounds on activation of complement, a known mediator of the procoagulant activity response. Stroma-free hemoglobin, hematin, purified hemoglobin Ao, and methemoglobin were all found to cleave complement fraction C3 to C3a but at concentrations much higher than those required for procoagulant activity. The data suggest that heme itself may be responsible for the procoagulant effect of stroma-free hemoglobin solutions. PMID- 1740632 TI - Time course of serum protein changes after strenuous exercise of the forearm flexors. AB - The time course of changes in serum proteins and other blood constituents after eccentric exercise of the forearm flexors by six nonweight-trained female subjects (age, 19.7 +/- 1.9 years) was investigated. Eccentric muscle actions are those in which the muscle lengthens as it exerts force, as when a person lowers a weight. Serum levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, myoglobin, as well as urea nitrogen, uric acid, creatinine, calcium, and phosphorus were examined before and for 6 days after exercise. Creatine kinase increased dramatically (peak value ranged from 6740 to 24,200 U/L) and aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and myoglobin followed the same time course as creatine kinase, but their peak values were lower. These proteins did not increase significantly until 48 hours after exercise and reached peak values 3 to 5 days after exercise. Alkaline phosphatase, gamma-glutamyl transpeptidase, uric acid, urea nitrogen, creatinine, calcium, and phosphorus showed no change. There is either a delay in muscle protein release by damaged muscle fibers, or the proteins are unable to leave the interstitial area for the 24 to 48 hour period after exercise. Because of the long delay, care should be taken when blood protein levels are interpreted in persons who have exercised strenuously (even if only for a short period of intense effort) several days before any diagnostic tests are performed. PMID- 1740633 TI - Pharmacologic properties of an unfractionated heparin butyryl derivative with long-lasting effects. AB - This article reports on the pharmacologic properties of an O-acylated butyryl derivative (C4-UH) of unfractionated heparin (UH). In a purified system, the ability of C4-UH to catalyze the inhibition of thrombin and of factor Xa in the presence of antithrombin III was similar to that of UH. Addition of albumin (10 mg/ml) to the reagents reduced the antithrombin and antifactor Xa catalytic potency of C4-UH 68-fold and 20-fold, respectively, and did not alter those of UH. As judged from the prolongation of the activated partial thromboplastin time and the thrombin clotting time, the anticoagulant activities of C4-UH were two times weaker than those of UH. After calibration against UH, the antifactor Xa specific and antithrombin-specific activities were two and 6.6 times lower, respectively. After bolus intravenous injection into rabbits, the apparent clearances of C4-UH were reduced 2.4 (antifactor Xa activity) and 3.2 times (antithrombin activity) in comparison with those of UH. This property accounted for the higher plasma concentrations generated during a constant infusion of the same dose. In the Wessler thromboplastin model, the minimum doses providing the maximum antithrombotic effect after bolus injection were equivalent for both compounds when expressed as antifactor Xa units; the duration of the antithrombotic effect of this derivative was prolonged, whereas the hemorrhagic potential was unaffected. This study opens a new concept for heparin derivatives having lower clearances and long-lasting effects. These properties could be linked to nonspecific binding of C4-UH to plasma proteins, thereby reducing the amount of free compound available to interact with antithrombin III. PMID- 1740634 TI - LD: the next 25 years. PMID- 1740635 TI - Reflections on Barsch's perspectives, and a few of my own. PMID- 1740636 TI - Learning disabilities: the changing landscape. PMID- 1740637 TI - Historical perspectives on dyslexia. AB - This article begins with an historical overview of the neurological aspects of dyslexia, which was originally seen as a member of the family of aphasias. That overview is followed by a brief review of familial and genetic factors in developmental dyslexia. The article then presents psycholinguistic models of dyslexia as they relate to the neurological concepts. Finally, the author reviews briefly the evolution of methods that have been successful in the remediation of dyslexia. PMID- 1740638 TI - Children with language disorders: natural history and academic success. AB - Children with developmental language disorders pose specific and unique problems for educators. This article addresses the continuing academic vulnerability of these children during the school years. We advance the position that their academic vulnerability results from the lifelong need to acquire language, to learn with language, and to apply language knowledge for academic learning and social development. Issues are addressed that relate to persistence of language deficits and learning in school. PMID- 1740639 TI - Perspectives on learning disabilities: the vectors of a new convergence. PMID- 1740640 TI - Predictors of self-esteem: the roles of parent-child perceptions, achievement, and class placement. AB - This study examined the relative influence on children's self-esteem of academic achievement, maternal self-esteem, maternal acceptance, and children's perception of their parents' acceptance of them. Subjects were students with learning disabilities in a self-contained class (n=31), similarly diagnosed students in resource room (n=35), students in compensatory education (n=30), and nondisabled students (n=30) from Grades 3 through 6. Results showed that for the self contained group, a child's perception of maternal and paternal acceptance plus the child's academic achievement score accounted for 58% of the variance in the child's self-esteem. None of the independent variables accounted for a significant proportion of the variance in the compensatory education and regular class groups. The self-esteem of the regular class students was significantly higher than that of the resource room students and the compensatory education students, but not significantly higher than that of the self-contained students. PMID- 1740641 TI - Neutrophil-induced immunoglobulin binding to erythrocytes involves proteolytic and oxidative injury. AB - Neutrophil-induced alterations in feline erythrocytes were studied to better understand the pathogenesis of erythrocyte destruction associated with inflammatory diseases. As in previous studies, addition of superoxide dismutase/catalase to a coculture of erythrocytes and activated neutrophils attenuated neutrophil-induced immunoglobulin G (IgG) binding. However, incubation of erythrocytes with hydrogen peroxide or neutrophil-derived anuclear cytoplasts (neutroplasts) failed to induce IgG binding. Addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to the erythrocyte-neutrophil coculture attenuated IgG binding. These observations suggest that neutrophil-derived serine protease activity is involved in IgG binding to erythrocytes. Further, incubation of erythrocytes with serine proteases, but not metalloproteases or sulfhydryl proteases, induced immunoglobulin binding. Freeze-fracture replicas of the erythrocyte membrane failed to demonstrate clustering of band 3 protein, suggesting that spatial rearrangement of band 3 protein was not the cause of the IgG binding. Neutrophil-induced IgG binding due to the combined action of proteases and oxidants may explain the accelerated destruction of erythrocytes in inflammatory diseases. PMID- 1740642 TI - Characterization of bilirubin transport system by human peripheral blood mononuclear cells. AB - Decreased immune responses have been observed in hyperbilirubinemic patients. This study investigates bilirubin transport into human peripheral blood mononuclear cells (PBMNCs). In vitro incubation of PBMNCs at 37 degrees C with 0 12 mg/dl bilirubin in solution with a fixed bovine serum albumin (BSA) concentration (3.0 g/dl) resulted in a dose-dependent increase of intracellular bilirubin in both monocytes and lymphocytes. Bilirubin uptake in monocytes was significantly higher (up to 2.7 times) than in lymphocytes under the same culture conditions. When PBMNCs were incubated with varying concentrations of bilirubin (0-16 mg/dl) in fixed BSA (3.0 g/dl) solution or at a fixed bilirubin/albumin molar ratio (0.4), the initial velocity of uptake in both cell fractions was proportional to the free (unbound to albumin) bilirubin concentration rather than the total bilirubin concentration. Bilirubin uptake by both cell fractions was significantly inhibited by treatment with metabolic inhibitors. Bilirubin uptake by monocytes continued to increase in parallel with incubation temperature from 0 degrees C to 40 degrees C, whereas uptake by lymphocytes reached a maximal level at 20 degrees C and remained constant thereafter. These results suggest that monocytes and lymphocytes incorporate bilirubin in proportion to the free bilirubin concentration and this function may rely on different energy-dependent mechanisms. PMID- 1740643 TI - Characterization of immunosuppressive functions of murine peritoneal macrophages induced with various agents. AB - Murine peritoneal macrophages (M phi s), induced with stimuli such as thioglycollate, zymosan A, OK-432, bacille Calmette-Guerin (BCG), or live Mycobacterium intracellulare, showed varying levels of inhibitory activity against the concanavalin A (Con A) blastogenic response of splenic T cells. All test M phi s significantly inhibited the interleukin 2 (IL-2)-producing ability of T cells but this inhibition was not enough to explain the observed reduction in T cell Con A mitogenesis. In contrast, they markedly inhibited IL-2-reactive T cell generation, and the inhibition was sufficient to cause the reduction in T cell mitogenesis. A general relationship was observed between immunosuppressive activity of a given M phi and its active oxygen-producing ability (measured in terms of chemiluminescence) in response to phorbol myristate acetate triggering (r = .84, P less than .005). However, the suppressor activity of test M phi s was not reduced by superoxide dismutase and catalase, indicating that active oxygen radicals themselves did not mediate the expression of the immunosuppressive activity of these M phi s. On the other ahnd, indomethacin (an inhibitor of prostaglandin synthesis) caused a partial reduction in their immunosuppressive activity. The suppressor activity of M phi s induced with intraperitoneal injection of recombinant interferon gamma (IFN-gamma) was markedly reduced in the presence of myoglobin, a scavenger for nitric oxide radical (NO.). Tumor necrosis factor alpha (TNF alpha) failed to affect Con A mitogenesis of splenic T cells, even in combination with IFN-gamma. On the other hand, unsaturated long-chain fatty acids including oleic, linoleic, linolenic, and arachidonic acids markedly reduced the T cell function. These findings suggest some important roles of prostaglandins, NO., and long-chain unsaturated fatty acids as mediators of the expression of immunosuppressive function of the peritoneal M phi s. PMID- 1740644 TI - Absence of interleukin 1 alpha radioprotection in tumor-bearing animals: elevated plasma levels of prostaglandin E versus a preexisting primed marrow. AB - Recombinant human interleukin 1 (IL-1) administered as a "priming" agent 24 h prior to hematopoietically lethal doses of total body irradiation (TBI) confers radioprotection to normal C57B1/6 (B6) mice, but not to B6 tumor-bearing animals (TBAs) known to have altered hematopoietic steady states. Using the Lewis lung tumor (LLca) in the B6 mouse, studies were carried out to determine whether the failure of IL-1 to radioprotect the LLca TBA was related to a preexisting "primed" hematopoietic state in the TBA or resulted from inhibition of myelopoietic activity associated with the production of prostaglandin E (PGE) by, or in response to, the tumor. Both normal B6 and LLca B6 TBAs were injected (every 24 h x 1-5) with 100 micrograms of indomethacin (IND) prior to the administration of IL-1. A single treatment with IND was sufficient to reduce the elevated levels of PGE found in the plasma of the TBAs. After five treatments, IND reduced the PGE level to below that of controls. Neither the acute nor the protracted IND treatment, however, affected the expansion of the stem and progenitor cell compartments of the marrow in the LLca TBA. Furthermore, no evidence of restoration of the radioprotective properties of IL-1 was observed in TBAs pretreated with IND. Collectively, these data suggest that the failure of IL 1 to provide radioprotection to the LLca TBA is not a direct result of the elevated plasma PGE levels associated with growth of the LLca tumor. In addition, these studies provide insight into the importance of examining in vivo effects of biological molecules in altered, as well as normal, physiological states. PMID- 1740645 TI - Fibronectin fragments stimulate tumor necrosis factor secretion by human monocytes. AB - Fibronectin (Fn) is a high molecular-weight glycoprotein that can influence many aspects of monocyte function. The purpose of this study was to determine whether Fn could stimulate monocyte tumor necrosis factor (TNF) secretion. Monocytes were isolated from the peripheral blood of healthy volunteers by density gradient centrifugation and adherence to plastic (2 h). Plasma Fn was purified from the blood by gelatin-Sepharose affinity chromatography. Monocytes were stimulated with Fn for 18 h and the supernatants were assayed for TNF activity using the L929 bioassay. Intact Fn stimulated the secretion of TNF in a dose-dependent manner. Intact Fn-induced TNF secretion by monocytes was inhibited (50%) but not eliminated by the addition of the R-G-D-containing peptide GRGDSP. Limited proteolysis of the Fn molecule using insoluble chymotrypsin resulted in a fragment preparation that was dramatically more stimulatory than the intact Fn preparation. High-performance liquid chromatographic (HPLC) purification of the fragments demonstrated that at least two fragments were capable of stimulating TNF secretion. Further purification by affinity chromatography and HPLC localized the stimulatory activity to the 120-kd cell-binding fragment. The possibility that the stimulatory activity was the result of endotoxin contamination was ruled out using macrophages from C3H/Hej mice. These results suggest that Fn fragments are potentially important molecules for activation of monocytes and may stimulate monocyte cytotoxic activity. PMID- 1740646 TI - Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor. AB - Macrophages derived in vitro from bone marrow progenitors (bone marrow-derived macrophages, BMDMs) using either macrophage colony-stimulating factor (CSF-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as the myelopoietic stimulus display differential functional, morphological, and mRNA phenotypes. The data presented here demonstrate further that CSF-1- and GM-CSF-derived BMDMs differ in immunologic capacity. GM-CSF-derived BMDMs, when compared to CSF-1 derived BMDMs, showed greater cytolytic activity against tumor necrosis factor alpha (TNF-alpha)-resistant, but not TNF-alpha-sensitive, tumor targets. In contrast, CSF-1-derived BMDMs produced nitrite in response to lipopolysaccharide (LPS) alone, whereas GM-CSF-derived BMDMs required interferon gamma plus LPS treatment. The two BMDM populations also showed differential sensitivities to LPS for secretion of TNF-alpha and nitrite, but the maximal inducible amounts of these factors and prostaglandin E2 were similar between the BMDM populations. Lastly, GM-CSF-derived but not CSF-1-derived BMDMs showed an L-arginine-dependent listeriacidal activity. These results show that the functional heterogeneity of CSF-1- and GM-CSF-derived macrophages is limited and appears to result largely from differences in the activational signals required by each BMDM population to elicit a given function. PMID- 1740647 TI - Mouse T cell clones against Mycobacterium avium: identification of clones that modify resistance against atypical mycobacteria infection. AB - Mouse T cell clones against live Mycobacterium avium were generated from the spleens of BALB/c mice infected with M. avium TMC 702. Eighth clones were of the L3T4+ subset, whereas two were of Lyt2+ subset. Six of the L3T4+ T cell clones were of the TH1 subset whereas two were of the TH2 subset, judged on the profile of cytokine release. One of the Lyt2+ clones exhibited significant cytotoxicity against M. avium-infected mouse macrophages. Transfer of clones to nude BALB/c mice infected with M. avium was associated with insignificant changes in resistance for seven clones. One clone, of the L3T4+/TH2 subset, transferred significant resistance to the infection, also associated with infusion of supernatants from the clone, which was fully inhibited by neutralizing with anti interleukin 4. By contrast, infusion of one TH1 clone and the cytolytic Lyt2+ led to increased microbial growth in the spleens and livers of infected mice, which was not apparent on infusion with supernatants. Application of clones' supernatants on infected macrophages had marginal effects on M. avium growth and was not correlated with protective or suppressive activity. Overall, these results suggest that T cells may influence M. avium growth in vivo in a bidirectional manner and also suggest that interleukin 4 may be an important factor in host resistance to M. avium. PMID- 1740648 TI - Heterogeneity in the mobilization of cytoplasmic calcium by human polymorphonuclear leukocytes in response to fMLP, C5a and IL-8/NAP-1. AB - The visible excitation and emission wave-lengths of the recently developed fluorescent Ca2+ indicator fluo-3 permit analysis of the intracellular Ca2+ concentration, [Ca2+]i, in flow cytometry with a 488-nm argon laser. The role of [Ca2+]i in human polymorphonuclear leukocyte heterogeneity was investigated in response to formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and interleukin 8/neutrophil attractant/activation protein 1 (IL-8/NAP-1) by flow cytometry. The [Ca2+]i changes in different subpopulations within a heterogeneous cell suspension were resolved upon stimulation with fMLP. Using an anti-CD16 phycoerythrin-conjugated antibody and fluo-3 simultaneously, neutrophils affected and nonaffected in Ca2+ mobilization were distinguished in two patients suffering from glycogen storage disease type 1b. In normal neutrophils, a different time course of Ca2+ mobilization of neutrophil subpopulations immediately after stimulation with fMLP was detected. In addition, after stimulation with a low concentration of IL-8/NAP-1 (10(-10) M) two subsets of neutrophils appeared; one of them showed an increase in [Ca2+]i, while the other did not. These results indicate heterogeneity in the neutrophil signal transduction process involved in Ca2+ mobilization. Therefore, flow cytometric analyses can resolve changes in single-cell [Ca2+]i distribution patterns, which is important for the understanding of [Ca2+]i in neutrophil heterogeneous activation processes. PMID- 1740649 TI - Role for the cervical sympathetic trunk in regulating anaphylactic and endotoxic shock. AB - This study tests the hypothesis that spinal nerves projecting down the cervical sympathetic trunk contribute to the regulation of systemic immune responses. Decentralization or ablation (ganglionectomy) of the superior cervical ganglia (SCG), which receive innervation from spinal segments C8-T8, were found to reduce the pulmonary inflammatory response consequent to induction of anaphylaxis in rats sensitized to the nematode Nippostrongylus brasiliensis. Furthermore, the hypotensive responses to IV endotoxin were attenuated in sensitized rats by these operations, whereas decentralization without ganglionectomy protected against endotoxic shock in normal (unsensitized) rats. These results suggest that systemic inflammatory events are regulated by the cervical sympathetic nervous system at a level superior to the superior cervical ganglia. Further studies are warranted to investigate the role of the cervical and thoracic sympathetic nerves in the regulation of systemic immunological function. PMID- 1740650 TI - Differences in treatment history with manipulation for acute, subacute, chronic and recurrent spine pain. AB - Preference for treatment protocols used in the care of spine disorders are based more upon clinical impressions than upon systematic study of the pathology or treatment efficacy. As social emphasis moves to cost containment strategies, quantitative data is necessary to give guidance for rational policy decisions. This study sets a description of the clinical experience obtained in a group practice, teaching clinic engaged in management of spine disorders. The same subjects were separately reported as being broadly representative of those seen in private using a cash payment policy. Clinical characteristics were quantified on 241 patients. A total of 149 volunteered to complete follow up evaluations. The total number of treatment sessions were tallied to case resolution on all 241 patients and were evaluated by stratifying them according to chronicity of the chief complaint. The range of treatment for all cases was 1-22. Chronic complaints required the most care, with a mean of 8.2 sessions (F = 2.833, p = .014). Thoracic disorders required approximately half the care as lordotic spine regions (F = 2.372, p = .04). No differences were observed based upon descriptive classifications of entrapment, mechanical or muscular pain. All but 25 cases reached resolution well within 6 wk, requiring a mean of 3.8 (range 1-11) additional treatment sessions. PMID- 1740651 TI - The evolution and importance of spinal and chiropractic research. AB - From its discovery in 1895 to its current status, in which the World Federation of Chiropractic Meeting may be considered a prestigious international scientific conference, the evaluation of chiropractic can be viewed as a compression of the phases which medical and scientific evolution have followed over a much longer period. Chiropractic theory started primarily as a vitalistic philosophy justifying its treatment while the medical scientific community was rejecting vitalism. Both chiropractic and medical spine specialists went through a period of speculative theory in the first half of this century based upon either perceived neurological or pathological observations. There was a period of single theory preoccupation by chiropractors (the subluxation) and medical specialists (disc herniation) which brought these professions into conflict. The past decade has led to greater scientific exploration by both professions, with more national scientific discussion of the causes and treatment of spinal problems. The next decade, however, appears likely to require greater emphasis on social research into clinical effectiveness of treatments, prevention of back pain, patient satisfaction and quality assurance. This evolution should be considered the normal maturation of a health care profession. PMID- 1740652 TI - Pathoanatomic studies and clinical significance of lumbosacral zygapophyseal (facet) joints. AB - Low back pain, with or without pain referred to the leg, affects up to 85% of the population at some time during their lives, which places an enormous economic burden upon many world communities and costs the United States in excess of $13 billion per year. The role of the lumbosacral zygapophyseal (facet, interlamina) joints in the low back "facet" syndrome is briefly discussed, including the clinical symptomatology. The main purpose of this article is to provide preliminary morphological findings of histological studies of human cadaveric lower lumbosacral spines, which show some examples of how the zygapophyseal joints may be involved in dysfunction of mechanical origin. Statistical analysis of the frequency of these findings will be published when the histological study currently under way is completed. While it is not possible to correlate morphological changes in cadavers with pain, it appears that the zygapophyseal joints and their associated soft tissues could be a source of low back pain of mechanical origin, with or without referred pain to the leg. PMID- 1740653 TI - The reflex effects of spinal somatic nerve stimulation on visceral function. AB - This paper studies somatovisceral reflex responses in the cardiovascular organ, gastrointestinal tract, urinary bladder and adrenal medulla in anesthetized animals after eliminating emotional factors following somatic sensory stimulations. Various somatic sensory stimulations, including cutaneous, muscle and articular sensory stimulations, can produce differing autonomic reflex responses, depending on which visceral organs and somatic afferents are stimulated. Some responses have dominant sympathetic efferent involvement, whereas others have dominant parasympathetic efferent involvement. Some responses have propriospinal and segmental characteristics, while others have supraspinal and generalized characteristics in their reflex nature. These somatovisceral reflex responses may be functioning during spinal manipulative therapy in conscious humans. PMID- 1740654 TI - The effects of compression on the physiology of nerve roots. AB - The spinal roots connect the central and peripheral nervous systems. In doing so, the nerve roots pass through the spinal column, where they are located in narrow spaces, close to vertebrae and intervertebral discs. At these locations, nerve roots can be subjected to mechanical compression in association with, for example, disc herniation, spinal stenosis and spine trauma. In this article, basic aspects of the anatomy and physiology of nerve roots are reviewed. Nerve fiber arrangements, connective tissue layers and blood supply are described. The effects of compression on nerve root structure and function are summarized, based on experimental studies involving analyses of nerve function, nutrition, including blood flow, and edema formation in the nerve root. Pain mechanisms in nerve root compression are reviewed in relation to various clinical conditions. PMID- 1740655 TI - The anatomical basis for cervicogenic headache. AB - The neuroanatomical basis for cervicogenic headache is convergence in the trigeminocervical nucleus between nociceptive afferents from the field of the trigeminal nerve and the receptive fields of the first three cervical nerves. Only structures innervated by C1-C3 have been shown to be capable of causing headache. These are the muscles, joints and ligaments of the upper three cervical segments, but also include the dura mater of the spinal cord and posterior cranial fossa and the vertebral artery. PMID- 1740656 TI - Studies on the biomechanical effect of a spinal adjustment. AB - Manual treatment of spinal disorders is perhaps the most well-studied remedy for spine-related disorders. Clinical description and controlled studies provide only limited advances in knowledge because so little is known scientifically about manual treatment methods or the disorders to which they are directed. The common factor for all manual methods is that they apply an external load to the spine and its surrounding tissues. Merging of efforts by basic scientists, engineers and clinician-scientists can resolve some of the underlying scientific ambiguity surrounding these issues. This report reviews the seminal efforts in biomechanics that are emerging to describe and understand the treatment, the spinal disorder for which it is used and the physiological effects of the treatment. PMID- 1740657 TI - A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection. AB - Antibodies directed against antigens present on renal epithelial cells can cause membranous glomerulonephritis in experimental animals, which closely resembles the human form of this disease. However, most antibodies produced so far fail to cause the persistent and severe proteinuria that is seen in humans. In our search for new antibodies of this kind, we have now produced a monoclonal antibody (mAb) against mouse aminopeptidase A, a hydrolase that is present in the mouse kidney. The mAb (ASD-4) was prepared by fusion of mouse myeloma cells with splenocytes of Lou rats immunized with brush border (BB) membranes from mouse kidneys. ASD-4 is of the IgG1 subclass and reacts with a 140-kD protein as demonstrated by immunoprecipitation on radiolabeled BB membranes. In indirect immunofluorescence and immunoelectronmicroscopy of normal mouse kidneys, ASD-4 was diffusely present on the BB of the S1 and S2 segments of the proximal tubules, and on the cell membranes of the glomerular visceral epithelia. It also bound to cell membranes of nonglomerular endothelia, smooth muscle cells of arteries, and juxtaglomerular cells. After injection of ASD-4 into normal mice, an immediate homogeneous binding to the capillary wall was seen that gradually changed into a fine granular pattern after 1 d. This glomerular binding was followed by binding to the BB and basolateral membranes of the convoluted proximal tubules. Immediately after injection of ASD-4, a dose-dependent albuminuria occurred that lasted for at least 16 d. ASD-4 is thus a new rat mAb against a well-defined renal epithelial antigen that causes not only membranous glomerulonephritis after a single injection in the mouse, but also severe albuminuria. PMID- 1740658 TI - Glucocorticoid receptor-mediated suppression of the interleukin 2 gene expression through impairment of the cooperativity between nuclear factor of activated T cells and AP-1 enhancer elements. AB - The immunosuppressant hormone dexamethasone (Dex) interferes with T cell-specific signals activating the enhancer sequences directing interleukin 2 (IL-2) transcription. We report that the Dex-dependent downregulation of 12-O tetradecanoyl-phorbol-13-acetate (TPA) and calcium ionophore-induced activity of the IL-2 enhancer are mediated by glucocorticoid receptor (GR) via a process that requires intact NH2- and COOH-terminal and DNA-binding domains. Functional analysis of chloramphenicol acetyltransferase (CAT) vectors containing internal deletions of the -317 to +47 bp IL-2 enhancer showed that the GR-responsive elements mapped to regions containing nuclear factor of activated T cells protein (NFAT) (-279 to -263 bp) and AP-1 (-160 to -150 bp) motifs. The AP-1 motif binds TPA and calcium ionophore-induced nuclear factor(s) containing fos protein. TPA and calcium ionophore-induced transcriptional activation of homo-oligomers of the NFAT element were not inhibited by Dex, while AP-1 motif concatemers were not stimulated by TPA and calcium ionophore. When combined, NFAT and AP-1 motifs significantly synergized in directing CAT transcription. Such a synergism was impaired by specific mutations affecting the trans-acting factor binding to either NFAT or AP-1 motifs. In spite of the lack of hormone regulation of isolated cis elements, TPA/calcium ionophore-mediated activation of CAT vectors containing a combination of the NFAT and the AP-1 motifs became suppressible by Dex. Our results show that the IL-2-AP-1 motif confers GR sensitivity to a flanking region containing a NFAT element and suggest that synergistic cooperativity between the NFAT and AP-1 sites allows GR to mediate the Dex inhibition of IL-2 gene transcription. Therefore, a Dex-modulated second level of IL-2 enhancer regulation, based on a combinatorial modular interplay, appears to be present. PMID- 1740659 TI - Expression of the Qa-2k phenotype encoded by the Q5k gene on the surface of tumor cells derived from H-2k mice. AB - Immunological and biochemical characteristics of the Qa-2 murine nonclassical histocompatibility class 1 antigen expressed on tumor cells derived from H-2k (Qa 2-) mice were studied. It was found that the Qa-2 antigen on normal H-2b lymphocytes reacted with Qa-2-specific monoclonal antibodies (mAbs) 34-1.2, 59 (both specific to the alpha 1/alpha 2 region) and 141-15.8 (specific to the alpha 3 domain), and the Qa-2 antigen on H-2k tumor cells (Qa-2k antigen) reacted with mAbs 59 and 141-15.8, but not with 34-1.2. The normal Qa-2 antigen was susceptible to treatment with phosphatidylinositol-specific phospholipase C, but the Qa-2k antigen was insensitive to it. By Northern hybridization, polymerase chain reaction (PCR) studies on cDNA, Southern hybridization, Western blotting, and nucleotide sequence analysis, the Q5k gene was identified as the gene encoding the Qa-2k antigen expressed on BW5147 lymphoma cells derived from a mouse of AKR strain (H-2k, Qa-2-). The nucleotide sequence of PCR-amplified BW5147 Q5k cDNA showed complete agreement with the reported sequence of exons 1-5 of the Q5k gene of C3H/He. It also showed complete deletion of the region corresponding to exons 6 and 7, and a very short coding region in exon 8, resulting in very short cytoplasmic domain of the product compared with regular class 1 antigens. These characteristics were expected from the reported Q5k genomic sequence. These results revealed that the Qa-2k antigen was distinct from the normal Qa-2 antigen expressed on H-2b lymphocytes although it cross-reacted with some Qa-2-specific mAbs. PMID- 1740660 TI - Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats. AB - Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell mediated in type. PMID- 1740661 TI - Polymorphisms in the tumor necrosis factor alpha (TNF-alpha) gene correlate with murine resistance to development of toxoplasmic encephalitis and with levels of TNF-alpha mRNA in infected brain tissue. AB - Murine resistance to development of toxoplasmic encephalitis (TE) has recently been mapped to the D region of the major histocompatibility complex (H-2). Since the gene for tumor necrosis factor alpha (TNF-alpha) is located 5' of the D region and TNF-alpha has been implicated as playing a role in neurological diseases, we were interested in determining the relationship of TNF-alpha production to TE resistance. We have demonstrated that resistance to TE in inbred mice can be correlated with specific restriction fragment length polymorphisms and microsatellite variants in the TNF-alpha gene. Mice that are susceptible to TE express elevated levels of TNF-alpha mRNA in brain tissue 6 wk after infection with the ME49 strain of Toxoplasma gondii. Resistant mice and all mice that are uninfected show no detectable TNF-alpha mRNA expression in brain tissue. Differences in the TNF-alpha gene between susceptible and resistant mice have been localized to the first intron, the promoter, and the 3' end of the TNF-alpha gene. These data implicate differences in regulation of TNF-alpha production in brain tissue as contributing to differences in susceptibility to development of TE. PMID- 1740662 TI - Activation events during thymic selection. AB - During their differentiation in the mouse thymus, CD4+8- cells undergo several of the sequential changes observed upon normal activation of mature, peripheral CD4+ lymphocytes. Expression of CD69, an early activation marker, is first observed on a minority of cells at the T cell receptor (TCR)lo/med double-positive stage, is maximal (50-90%) on heat-stable antigen (HSA)hi TCRhi double-positive, HSAhi TCRmed CD4+8lo, and HSAhi TCRhi CD4+8- cells, and is downmodulated at the mature HSAlo CD4+8- stage. In contrast, CD44, a late activation marker, is selectively expressed at the HSAlo stage. The set of lymphokines that CD4+8- thymocytes can produce upon stimulation also characteristically expands from mainly interleukin 2 (IL-2) at the HSAhi stage, to IL-2 and very large amounts of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) at the HSAlo stage. 1 in 30 HSAlo CD4+8- adult thymocytes secrete IL-4 upon stimulation through their TCR. This frequency is 25% of the frequency of IL-2 producers, about 100-fold above that of peripheral (mainly resting) CD4+ T cells. With time after their generation in organ culture, CD4+8- thymocytes lose their capacity to secrete IL-4, IL-5, and IFN-gamma, but not IL-2. Similarly, the frequency of IL-4, but not of IL-2, producers progressively decreases after emigration to the periphery as judged by direct comparison between thymic and splenic CD4+ cells in newborns, or by following the fate of intrathymically labeled CD4+8- cells in adults after their migration to the spleen. This sequence suggests that thymic selection results from an activation process rather than a simple rescue from death at the double-positive stage, and shows that the functional changes induced after intrathymic activation, although transient, are still evident after export to the periphery. PMID- 1740663 TI - Induction of monocytic differentiation and NF-kappa B-like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells. AB - The effects of human immunodeficiency virus 1 (HIV-1) infection on cellular differentiation and NF-kappa B DNA binding activity have been investigated in a new model of myeloid differentiation. PLB-985 cells represent a bipotential myelomonoblastic cell population capable of either granulocytic or monocytic differentiation after induction with appropriate inducers. By virtue of the presence of CD4 on the cell surface, PLB-985 cells were chronically infected with HIV-1 strain IIIB. PLB-IIIB cells clearly possessed a more monocytic phenotype than the parental myeloblasts, as determined by differential staining, increased expression of the myeloid-specific surface markers, and transcription of the c fms proto-oncogene. NF-kappa B binding activity was inducible by tumor necrosis factor and phorbol myristate acetate in PLB-985. However, in PLB-IIIB cells, constitutive expression of a novel NF-kappa B complex was detected, composed of proteins ranging between 70 and 110 kD. These proteins interacted specifically with the symmetric NF-kappa B site from the interferon beta (IFN-beta) promoter. Mutations affecting the 5' guanine residues of the kappa B site were unable to compete for these NF-kappa B-related proteins. Inducibility of endogenous IFN beta and IFN-alpha RNA was also increased in PLB-IIIB cells. These studies indicate that HIV-1 infection of myelomonoblastic cells may select for a more mature monocytic phenotype and that unique subunit associations of NF-kappa B DNA binding proteins may contribute to differential NF-kappa B-mediated gene expression. PMID- 1740664 TI - Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection. AB - Dendritic cells (DC), in general, and pulmonary DC, in particular, are a heterogeneous population of cells, their phenotype and function being dependent on their anatomic location, their state of activation, and the regulatory effect of locally secreted cytokines. Using a novel microdissection technique, the epithelium from the trachea and entire airway system was harvested, and the contained DC isolated at greater than 90% purity. The phenotype and function of these airway DC (ADC) was compared to DC isolated, at greater than 90% purity, from the parenchyma of the same lung. In contrast to lung DC (LDC), ADC did not express intercellular adhesion molecule 1 (ICAM-1) in situ, the amount of immune associated antigen (Ia) expressed was less (as determined by immunoperoxidase staining and immunopanning), and greater than 50% of ADC displayed Fc receptors (FcR). The majority of LDC were ICAM-1+, less than 5% expressed FcR, and all were intensely Ia+. Airway DC were most numerous in tracheal epithelium, but they were also present in small numbers in the epithelium of the most distal airways. Their numbers increased in all segments of the tracheobronchial epithelium in response to the administration of IFN-gamma. ADC were consistently more effective than LDC in presenting soluble (hen egg lysozyme) and particulate (heat-killed Listeria monocytogenes) antigens to antigen-sensitized T cells. By contrast, LDC were significantly more efficient in stimulating the proliferation of nonsensitized T cells in an autologous mixed leukocyte reaction. These data suggest that in normal animals, intraepithelial DC of airways share many attributes with Langerhans cells of the skin. Interstitial LDC, by contrast, reside in an environment where they may be exposed to a different set of regulatory factors and where they have progressed to a more advanced stage of differentiation than ADC. Both groups of DC are, however, heterogeneous, reflecting the continuous turnover that these cells undergo in the lung. PMID- 1740665 TI - Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response. AB - Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen. PMID- 1740666 TI - Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL 4 mutant cells. AB - It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo. PMID- 1740667 TI - The AP-1 site at -150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter. AB - Stimulation of T cells with antigen results in activation of several kinases, including protein kinase C (PKC), that may mediate the later induction of activation-related genes. We have examined the potential role of PKC in induction of the interleukin 2 (IL-2) gene in T cells stimulated through the T cell receptor/CD3 complex. We have previously shown that prolonged treatment of the untransformed T cell clone Ar-5 with phorbol esters results in downmodulation of the alpha and beta isozymes of PKC, and abrogates induction of IL-2 mRNA and protein. Here we show that phorbol ester treatment also abolishes induction of chloramphenicol acetyltransferase activity in Ar-5 cells transfected with a plasmid containing the IL-2 promoter linked to this reporter gene. The IL-2 promoter contains binding sites for nuclear factors including NFAT-1, Oct, NF kappa B, and AP-1, which are all potentially sensitive to activation of PKC. We show that induction of a trimer of the NFAT and Oct sites is not sensitive to phorbol ester treatment, and that mutations in the NF-kappa B site have no effect on inducibility of the IL-2 promoter. In contrast, mutations in the AP-1 site located at -150 bp almost completely abrogate induction of the IL-2 promoter, and appearance of an inducible nuclear factor binding to this site is sensitive to PKC depletion. Moreover, cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the IL-2 promoter in minimally stimulated T cells. Our results indicate that the AP-1 site at -150 bp represents a major, if not the only, site of PKC responsiveness in the IL-2 promoter. PMID- 1740668 TI - A thyroxine-containing peptide can induce murine experimental autoimmune thyroiditis. AB - A synthetic peptide based on a sequence containing thyroxine at position 2553 in thyroglobulin (Tg), and already shown to be recognized by two clonotypically distinct murine Tg autoreactive T cell hybridomas, can trigger primed lymph node cells to transfer thyroiditis to naive recipients. Donor lymph node cells could be prepared from mice immunized either with intact mouse Tg or with this peptide itself. After a second exposure to the priming antigen in vitro, both these populations induced 100% thyroiditis in recipient animals. The importance of the T4 residue in the development of disease was demonstrated by the failure of Tg tryptic peptides depleted of T4 to stimulate pathogenic effectors in vitro, even when the lymph node cells had been taken from mice primed with whole Tg. We conclude that this T4-containing 12mer sequence is a major thyroiditogenic epitope in CBA/J mice although we cannot exclude the possibility that there are other pathogenic epitopes present in the whole Tg molecule. PMID- 1740669 TI - Modification of potassium channel kinetics by amino group reagents. AB - We have examined the actions of several amino group reagents on delayed rectifier potassium channels in squid giant axons. Three general classes of reagents were used: (1) those that preserved the positive charge of amino groups; (2) those that neutralize the charge; and (3) those that replace the positive with a negative charge. All three types of reagents produced qualitatively similar effects on K channel properties. Trinitrobenzene sulfonic acid (TNBS) neutralizes the peptide terminal amino groups and the epsilon-amino group of lysine groups. TNBS (a) slowed the kinetics of macroscopic ionic currents; (b) increased the size of ionic currents at large positive voltages; (c) shifted the voltage dependent probability of channel opening to more positive potentials but had no effect on the voltage sensitivity; and (d) altered several properties of K channel gating currents. The actions of TNBS on gating currents suggest the presence of multiple gating current components. These effects are not all coupled, suggesting that several amino groups on the external surface of K channels are important for channel gating. A simple kinetic model that considers the channel to be composed of independent heterologous subunits is consistent with most of the modifications produced by amino group reagents. PMID- 1740670 TI - Virus-induced obesity in mice: association with a hypothalamic lesion. AB - In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre-obese animals shortly after intracerebral infection was mapped using immunocytochemical procedures. A distinctive pattern of cell labeling was found, extending from the anterior periventricular hypothalamus ventrally and caudally toward the posterior hypothalamus. The heaviest concentration of labeled cells was found in the arcuate-ventromedial area. Viral antigen-containing cells were not found in obese brain specimens. However, the latter revealed, by glial fibrillary acidic protein immunostaining, a gliotic lesion of the hypothalamus that approximated topographically the pattern of virus tropism. Examination of the arcuate area revealed a significant reduction in tyrosine hydroxylase immunoreactive and pro-opiomelanocortin mRNA positive perikarya. We suggest that the loss of critical populations of hypothalamic neurons as a result of an antecedent viral infection led ultimately to the development of morbid obesity. PMID- 1740671 TI - Expression of various NCAM isoforms in human embryonic muscles: correlation with myosin heavy chain phenotypes. AB - Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development. PMID- 1740672 TI - Pathology of HIV-1 infection of the central nervous system. A review. PMID- 1740673 TI - Occurrence of oligodendrocytes within astrocytes in demyelinating lesions. AB - We investigated the fine structural details of the presence of apparently newly formed oligodendrocytes within reactive astrocytes in white matter lesions obtained by biopsy from seven cases (3 multiple sclerosis (MS); 3 progressive multifocal leukoencephalopathy (PML); 1 with nonspecific reactive changes next to a sarcoid granuloma). Intact oligodendrocytes were found within astrocytic cytoplasm in two acute MS lesions and also in the reactive white matter lesion. The internalized cells appeared to lie within membrane-bound vacuoles. Formation of rudimentary junctions was observed between the internalized cells and host astrocytes. Sometimes more than one oligodendrocyte was seen in the same astrocyte. Our study suggests that this newly recognized interaction between astrocytes and oligodendrocytes is not restricted to acute MS lesions and probably represents emperipolesis rather than phagocytosis. This apparently nonspecific finding may be expected in any lesion with a proliferation of astrocytes and oligodendrocytes. The precise mechanism of this phenomenon or its functional significance is not entirely clear. PMID- 1740674 TI - The twitcher mouse: immunocytochemical study of Ia expression in macrophages. AB - The cells expressing immune response associated antigen (Ia) were investigated in the nervous system of the twitcher mouse (an authentic murine model of globoid cell leukodystrophy in humans). With immunocytochemistry using a monoclonal antibody against Mac-1 antigen, many Mac-1 immunoreactive cells (Mac-1 positive cells) were detected in the central as well as the peripheral nervous systems (CNS and PNS). In the CNS, Mac-1 positive cells in the gray matter showed cellular morphology of ramified microglia with delicate cellular processes, while in the white matter Mac-1 positive cells were more plump in shape. Ia expressing cells (Ia positive cells) were also largely confined to the white matter. About 10% of the Mac-1 positive cells were Ia positive. The Ia and Mac-1 positive cells were slender and spindle shaped, and morphologically similar to Ia positive cells in the peripheral nerves while the cells expressing Mac-1 only were more plump in shape. With immunoelectron microscopy, however, both slender Ia positive and plump Ia negative and Mac-1 positive cells revealed electron lucent cytoplasmic vacuoles containing characteristic tubular inclusions of globoid cell leukodystrophy. The results suggest that Ia positive cells are a subset of macrophages in the CNS. Whether Ia expression was induced to "endogenous" microglia or whether Ia expressing cells were exogenous cells infiltrated in the CNS in response to pathological lesions is yet to be determined. PMID- 1740675 TI - Kunitz protease inhibitor-containing amyloid beta protein precursor immunoreactivity in Alzheimer's disease. AB - The amyloid beta protein (beta/A4) that is deposited in senile plaques and in cerebral vessels in Alzheimer's disease (AD) is derived from a larger membrane associated glycoprotein, the amyloid beta protein precursor (APP). The gene encoding APP produces at least four major transcripts. Three of the four transcripts contain an alternatively-spliced exon encoding a Kunitz protease inhibitor domain (KPI). We now report the results of a series of experiments using novel immunohistochemical reagents to anatomically localize beta/A4, APP, and KPI-containing forms of APP (APP-KPI) in the hippocampal formation and temporal neocortex. A new monoclonal antibody against beta/A4 recognized senile plaques and vascular amyloid, but no cellular elements. Anti-APP and anti-KPI monoclonal antibodies stained neurons, including proximal axons and dendrites. The neuritic component of some plaques in patients with AD and in elderly control individuals were also immunoreactive for both APP and APP-KPI. Quantitative assessment of senile plaques in temporal neocortex showed that, on average, about one-third of beta/A4 immunoreactive plaques stained with either anti-APP or anti KPI. Amyloid beta protein precursor and APP-KPI immunoreactivity were also found in the white and grey matter vessels of both AD patients and control individuals. These results suggest that KPI-containing forms of APP are present in dystrophic neurites of senile plaques, and normally in neurons, neuronal processes, and in the vascular compartment in the brain. Thus, APP-KPI is in a position to be intimately associated with beta/A4 deposition in the neuropil, in plaques and in amyloid angiopathy. PMID- 1740676 TI - Lumpectomy and radiation: improving the outcome. PMID- 1740677 TI - Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study. AB - PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors. PMID- 1740678 TI - Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients with Hodgkin's disease: a phase I/II study. AB - PURPOSE: As bone marrow toxicity is the major limitation of the optimal administration of chemotherapy, we investigated whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) could prevent myelotoxicity or accelerate hematopoietic recovery after mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy. PATIENTS AND METHODS: Twenty-four previously untreated patients with Hodgkin's disease were included in a phase I/II study in which standard MOPP chemotherapy was followed by 5 days of GM-CSF at every other cycle. Patients were entered sequentially to receive one of four dosc levels (2, 4, 8, and 16 micrograms/kg of glycoprotein; 1.4, 2.8, 5.5, and 11.0 micrograms/kg of protein) and were randomly allocated to either 24-hour continuous intravenous (IV) infusion or twice daily subcutaneous (SC) injection of rhGM-CSF. RESULTS: WBC counts (mainly neutrophils, eosinophils, and monocytes) were significantly higher in cycles with rhGM-CSF than in cycles with MOPP alone. The total number of days of leukopenia (WBC count less than or equal to 2.0 x 10(9)/L) and neutropenia (absolute neutrophil count [ANC] less than or equal to 1.0 x 10(9)/L) was reduced in cycles with rhGM-CSF from 6.3 to 0.8 days and from 5.4 to 1.0 days, respectively. All dose levels of rhGM-CSF were effective in increasing the ANC, but only at the dose levels of 8 and 16 micrograms/kg did this significantly affect the scheduling of chemotherapy. Mild and reversible adverse reactions included low-grade fever, chest/bone pain, myalgias, erythemia, headache, fatigue, and periorbital edema. CONCLUSIONS: rhGM CSF can be administered safely to patients with Hodgkin's disease and results in improved hematologic recovery after MOPP. Full-dose chemotherapy can be administered on time, resulting in an increase in the overall tolerated dose of myelosuppressive drugs when compared with historical controls. SC administration proved to be at least as effective as continuous IV infusion and should be preferred. PMID- 1740679 TI - Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor. AB - PURPOSE: The study was undertaken to improve the results of intensive chemotherapy in chronic myelogenous leukemia (CML) in accelerated (CML-AP) and blastic phases (CML-BP) by the addition of granulocyte-macrophage colony stimulating factor (GM-CSF) as supportive therapy. PATIENTS AND METHODS: Forty eight patients were treated with daunorubicin 120 mg/m2 intravenously on day 1, cytarabine (ara-C) 1.5 g/m2/d by continuous infusion over 24 hours for 4 days, and Solu-Medrol (methylprednisolone; The Upjohn Co, Kalamazoo, MI) 100 mg/d for 5 days, followed on day 5 by GM-CSF 125 micrograms/m2/d over 6 hours until recovery of granulocyte count above 2.0 x 10(3)/microliters. Twenty-four patients had CML BP, and 24 had CML-AP. RESULTS: During remission induction, 45 patients (94%) developed febrile episodes (fever of unknown origin, 23 patients [48%]; documented infections, 22 patients [46%]). The median time to recovery of granulocyte count above 0.5 x 10(3)/microliters was 29 days and to platelet count above 30 x 10(3)/microliters, 28 days. Overall, 14 of 48 patients (29%) achieved a complete hematologic remission (CHR), and seven (15%) reverted to a second chronic phase. CHR was noted in eight of 24 patients with CML-BP (33%), and in six of 24 patients with CML-AP (25%). Cytogenetic responses were observed in 11 patients (23%), but were transient. Sixteen patients developed either fluid retention, hypotension, pleuropericardial effusions, or pericarditis, or a combination of these side effects. These side effects were severe in four patients and are likely to be disease-associated, as a similar regimen of intensive chemotherapy and GM-CSF at the same dose and schedule in acute lymphocytic leukemia was not associated with these side effects. CONCLUSIONS: The results pertinent to remission rates, induction mortality, myelosuppression profile and related complications, and overall survival were not significantly improved compared with previous experience. In summary, the results of intensive chemotherapy in CML-transformed phases remain poor, despite the addition of GM CSF as a supportive measure. PMID- 1740680 TI - Gemcitabine in leukemia: a phase I clinical, plasma, and cellular pharmacology study. AB - PURPOSE: Phase I clinical and in vitro studies of gemcitabine (2',2' difluorodeoxycytidine; dFdC) have demonstrated that the accumulation rate of dFdC 5'-triphosphate (dFdCTP) in mononuclear and leukemia cells is saturated when plasma or extracellular dFdC levels exceed 15 to 20 mumol/L. Thus, we designed a phase I study to maximize the accumulation of dFdCTP by leukemia cells by administering dFdC at 10 mg/m2/min, a dose rate calculated to produce steady state plasma dFdC levels that exceed 15 to 20 mumol/L. PATIENTS AND METHODS: The treatment intensity was increased in patients (n = 22) with relapsed or refractory acute leukemia or chronic myelogenous leukemia (CML) in blast crisis by prolonging the infusion duration but maintaining the same rate. Doses of dFdC between 1,200 mg/m2 and 6,400 mg/m2 were administered weekly for 3 weeks. RESULTS: The maximum-tolerated dose was 4,800 mg/m2 infused over 480 minutes. The mean steady-state dFdC level in plasma of all infusions was 26.5 +/- 9 mumol/L (n = 19). The accumulation rates of dFdCTP in circulating leukemia cells varied greatly among patients but remained linear in eight patients infused for 120 to 240 minutes, and up to or beyond 360 minutes in five of eight additional patients. Elimination of dFdCTP was significantly related to its cellular concentration: blasts with greater than 450 mumol/L dFdCTP exhibited biphasic elimination, whereas blasts with lower dFdCTP concentrations exhibited linear kinetics. Biphasic elimination was associated with higher dFdCTP areas under the concentration-times-time curve (AUCs) and greater inhibition of DNA synthesis. CONCLUSION: Studies of the cellular pharmacology and pharmacodynamics of dFdC may be useful in optimizing protocol designs for leukemia. PMID- 1740681 TI - Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients. AB - PURPOSE: Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF). PATIENTS AND METHODS: All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years. RESULTS: Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012). CONCLUSION: S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node negative breast cancer patients with small, ER-positive tumors. PMID- 1740682 TI - Carboplatin: an active drug in metastatic breast cancer. AB - PURPOSE: The study was undertaken to assess the antitumor activity of carboplatin 400 mg/m2 intravenously every 4 weeks in metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-four MBC patients without any prior exposure to chemotherapy entered the study. All patients had measurable disease in at least one site and were assessable for response and toxicity. RESULTS: Of 34 assessable patients, 12 obtained a complete (one) or partial (11) response to carboplatin, resulting in an overall response rate of 35% (95% confidence interval, 19.8% to 53.5%). The median duration of response was 8 months (range, 2+ to 12 months). Responses were seen in lymph nodes (four of six), lung (five of nine), skin and soft tissues (four of nine), breast (two of eight), and liver (three of 11), but not in measurable lytic lesions of the bone. Toxicity was mild, mainly consisting of emesis (81% of the patients; 66% of the courses), leukopenia of World Health Organization (WHO) grade 1 to 2 (47% of the patients; 18% of the courses), and thrombocytopenia (12% of the patients; 3% of the courses). There were no cases of life-threatening toxicity, although one patient developed grade 4 thrombocytopenia without bleeding. Of 22 patients who did not respond to carboplatin, 18 received salvage therapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF; 15 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; one patient); or hormones (two patients). Objective responses to CAF and hormonal therapy were seen in 11 of 15 and two of two patients, respectively. The remaining patient did not respond to CMF salvage chemotherapy. Overall, the response rate to either first-line carboplatin or second-line salvage therapy was 73.5% (25 of 34 patients). After a median follow-up time of 22 months, the median survival was 19 months. CONCLUSIONS: Carboplatin is an active drug in MBC patients without previous exposure to chemotherapy. In our study, the use of an experimental drug as first-line single-agent treatment in MBC did not have a negative influence on patient survival, as the majority of the carboplatin nonresponding patients could be salvaged with a conventional therapeutic regimen. PMID- 1740683 TI - Aromatase activity and estradiol in human breast cancer: its relationship to estradiol and epidermal growth factor receptors and to tumor-node-metastasis staging. AB - PURPOSE: The present report attempts to clarify whether there is a relationship between aromatase activity (ARAC) and estradiol (E2), hormonal receptors, E2 receptor (ER), and epidermal growth factor receptor (EGFR), as well as with tumor stage and histopathology in human breast cancers. MATERIALS AND METHODS: We studied 225 breast carcinomas, 67 of which were premenopausal and 158 postmenopausal. In each sample, ARAC, EGFR, ER, and E2 were quantified. ARAC was quantified by Thompson and Siiterii's method, EGFR was quantified with a two point assay method using radioactive iodine (125I)-EGF as ligand, and ER was measured by the Scatchard method using 3H-E2. E2 was quantified by radioimmunoassay in the diethylether tumor extract. RESULTS: ARAC was found in 64% of the cancers studied. There is a strong direct association between ARAC and tumor size in postmenopausal patients (P = .001). In the postmenopausal group, the proportion of ARAC-positive (ARAC+) tumors is significantly higher among ER positive (ER+) than ER-negative (ER-) ones (P less than .001). ER+ tumors also have significantly higher levels of E2 than do ER- ones (P less than .0001); similarly, ARAC+ tumors have significantly higher levels of E2 than do ARAC- ones (P less than .0001). There is a significant multiple linear correlation between the log of the levels of ARAC, ER, and EGFR and the log of tumor E2 (P less than .0001). The correlation coefficients obtained show that ARAC and ER have a positive effect on tumor E2. CONCLUSION: The results obtained suggest the importance of tumor ARAC in the tumoral levels of E2 and reinforce the possible biologic significance of tumor ARAC, especially in postmenopausal breast carcinoma patients. PMID- 1740684 TI - Pulmonary function tests after whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. AB - PURPOSE: Because of the scarcity of information regarding long-term follow-up of pulmonary function after whole-lung irradiation, a prospective study was started at the University of Florida in 1979 to evaluate pulmonary function after treatment with whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. PATIENTS AND METHODS: Between 1979 and 1984, 57 osteogenic sarcoma patients with no evidence of metastatic disease at diagnosis received adjuvant therapy consisting of whole-lung irradiation (with the heart shielded) followed by Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). The whole-lung irradiation schema was 1,600 cGy in 10 fractions with 8-MV x-rays via anterior and posterior fields. This was followed by five cycles of Adriamycin for a total dose of 450 mg/m2. Pulmonary function tests (PFTs) consisting of spirometry, lung volumes, and diffusing capacity were obtained before the whole-lung irradiation, at 6 and 12 months after irradiation, and at yearly intervals thereafter. RESULTS: At the time of analysis, 28 of the 57 patients were available for study, with a mean follow-up of 42 months (range, 6 to 77 months). Follow-up pulmonary function testing revealed decreased forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) during the first 6 to 12 months after whole lung irradiation. These values returned to baseline during the second-year posttherapy and remained at baseline throughout the remainder of the follow-up period. Changes in lung volumes demonstrated a similar early trend, with significant decreases in total lung capacity (TLC) and functional residual capacity (FRC) at 6 to 12 months. These changes, however, did not improve significantly during the remainder of the follow-up period. Diffusing capacity of the lungs for carbon monoxide (DLCO) also reached a nadir at 6 to 12 months after whole-lung irradiation, with resolution by 2 years and maintenance of at least baseline values for the remainder of the follow-up period. CONCLUSIONS: Treatment with whole-lung irradiation and Adriamycin, as given in this study, caused no significant sequelae, as demonstrated by pulmonary function testing during the mean follow-up period of 42 months, although a mild, transient restrictive ventilatory defect occurred at 6 to 12 months after treatment. PMID- 1740685 TI - Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy. AB - PURPOSE: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials. PMID- 1740686 TI - Irradiated blood products to prevent graft-versus-host disease. PMID- 1740687 TI - The dissonance mutation at the no-on-transient-A locus of D. melanogaster: genetic control of courtship song and visual behaviors by a protein with putative RNA-binding motifs. AB - Genetic and molecular results are here presented revealing that the dissonance (diss) courtship song mutation is an allele of the no-on-transient-A (nonA) locus of Drosophila melanogaster. diss (now called nonAdiss) was originally isolated as a mutant with aberrant pulse song, although it was then noted to exhibit defects in responses to visual stimuli as well. The lack of transient spikes in the electroretinogram (ERG) and optomotor blindness associated with nonAdiss are shown to be similar to the visual abnormalities caused by the original nonA mutations. nonAdiss failed to complement either the ERG or optomotor defects associated with four other nonA mutations. However, all four of these nonA mutants--which were isolated on visual criteria alone--sang a normal courtship song. nonAdiss complemented at least three of the nonA mutations with regard to the singing phenotype, as assessed by a new method for temporal analysis of the male's pulse song. Both visual and song abnormalities caused by nonAdiss were rescued by P-element-mediated transformation with overlapping 11 and 16 kilobase (kb) fragments of genomic DNA (originally cloned from the nonA locus by Jones and Rubin, 1990). Analysis of behavioral phenotypes in transformed flies carrying mutagenized versions of the 11 kb genomic fragment (in a nonAdiss genomic background) localized the rescuing DNA to a region containing an open reading frame that encodes a polypeptide (NONA) with similarity to a family of RNA binding proteins. Immunohistochemical determination of NONA's spatial and temporal expression revealed that it is localized to the nuclei of cells in many neural and non-neural tissues, at all stages of the life cycle after very early in development. Genetic connections between the control of two quite different behaviors--reproductive and visual--are discussed, along with precedences for generally expressed gene products playing roles in specific behaviors. PMID- 1740688 TI - Color selectivity of neurons in the inferior temporal cortex of the awake macaque monkey. AB - We tested the color selectivity of neurons in the inferior temporal (IT) cortex of two awake macaque monkeys. A color stimulus was presented at the center of the visual field while the animal performed a fixation task. The responses of single units to various colors were recorded and were plotted in a color space. The color space was based on the CIE (Commission Internationale de l'Eclairage) chromaticity diagram. Quantitative analysis of the color selectivity was performed using a standard set of colors that were evenly distributed in the color space. Sixty-five neurons recorded from eight guide tubes implanted in anterior part of IT cortex were tested quantitatively, and their color selectivity was statistically evaluated. Forty-six of them (71%) were classified as color selective. Color-selective cells responded to some colors but not to others, and we called the responsive region in the color space the "color field." The location and the size of a cell's color field were largely independent of the luminance of the stimulus. About 80% of the color-selective neurons had color fields consisting of a single responsive region that were restricted in some part of the color space, and the remaining cells had more than one responsive region within the color space. Preferred hues of the color-selective neurons differed from cell to cell. The population of cells together covered nearly all of the color space. There was a tendency for more color-selective cells to be less sensitive to white and desaturated cyans. Some of the cells with color fields that consisted of more than one responsive region were more sensitive to saturation of the stimulus than to its hue. Although previous electrophysiological studies in IT cortex emphasized the pattern selectivity of the neurons, our results suggest that color is an important factor in the role that IT cortex plays in the object recognition. PMID- 1740689 TI - Cooperative regulation of calcitonin gene-related peptide levels in rat sensory neurons via their central and peripheral processes. AB - Calcitonin gene-related peptide (CGRP) is present in both motor and sensory neurons and transported in the somatofugal direction. CGRP levels in sensory neurons are assumed to be regulated by NGF supplied from their peripheral targets. In cultured sensory neurons, however, a basal level of CGRP persists even without NGF. This suggests that some additional factors may be involved in regulation of CGRP levels of sensory neurons. The present study shows that chronic section of the sciatic nerve in the rat reduces CGRP levels in the lumbar dorsal root ganglia (DRG), whereas section of dorsal roots increases CGRP levels in the DRG. This increased CGRP level by dorsal rhizotomy was associated with enhancement of the CGRP mRNA expression in the DRG. Thus, CGRP expression in DRG appears to be regulated reciprocally via their central and peripheral processes. When the sciatic nerve had been cut 1 week previously, however, dorsal rhizotomy no longer increased CGRP levels in the lumbar DRG. Therefore, stimulation of CGRP synthesis in the DRG by dorsal rhizotomy may require the integrity of the peripheral processes. When NGF had been infused into the central stump of the cut sciatic nerve, dorsal rhizotomy again increased CGRP levels in the DRG, despite prior section of the peripheral processes. We conclude that CGRP expression in sensory neurons may be regulated by cooperative action of some factors derived via their central processes and NGF supplied from the peripheral targets. PMID- 1740690 TI - Distinct spatial and temporal expression patterns of K+ channel mRNAs from different subfamilies. AB - Different types of K+ channels play important roles in many aspects of excitability. The isolation of cDNA clones from Drosophila, Aplysia, Xenopus, and mammals points to a large multigene family with several distinct members encoding K+ channels with unique electrophysiological and pharmacological properties. Given the pivotal role K+ channels play in the fine tuning of electrical properties of excitable tissues, we studied the spatial and temporal basis of K+ channel diversity. We report the isolation of two putative K+ channels that define two new subfamilies based upon amino acid sequence similarities with other known K+ channels. Northern blot and in situ hybridization studies revealed differences in the spatial and temporal expression patterns for these two new clones along with mRNAs from other K+ channel subfamilies. Two of the K+ channels studied are predominantly expressed in the brain. One of the "brain-specific" K+ channels is first expressed after about 2 weeks of postnatal cerebellar development and remains at levels about 10-fold higher in the cerebellum than in the rest of the brain. PMID- 1740691 TI - Changes in the activity of units of the cat motor cortex with rapid conditioning and extinction of a compound eye blink movement. AB - Patterns of spike activity were measured in the pericruciate cortex of conscious cats before and after development of a Pavlovian conditioned eye blink response. Unit activity was tested with presentations of a click conditioned stimulus (CS) and a hiss discriminative stimulus (DS) of similar intensity to the click. Unit discharge in response to the CS increased after conditioning, but not after backward conditioning when conditioned reflexes (CRs) were not performed. Rates of spontaneous, baseline discharge were not increased after conditioning with respect to rates of discharge measured in the naive state. It appeared that an increase in the ratio of CS-elicited discharge to background activity, together with an increase in the number of units responding to the CS after conditioning, supported discrimination of the CS from the DS and performance of the conditioned blink response. This is the first detailed characterization of patterns of a rapidly conditioned Pavlovian response. Activation of units by the CS preceded the onset of the CR, supporting the hypothesis that the activity played a role in initiating the conditioned eye blink movement. Extinction with retention of performance of the CR was associated with perseverance of the increased unit discharge in response to the CS. Extinction with substantially reduced performance of the CR was associated with diminution of the unit response to the CS below levels found with conditioning. Averages of patterns of spike activity elicited by the CS after conditioning showed components of discharge with onsets of 8-40 msec (alpha 1), 40-72 msec (alpha 2), 72-112 msec (beta), and greater than 112 msec (gamma), corresponding to each of four separate excitatory EMG components of the compound blink CR. Each component increased in magnitude after conditioning, relative to levels found in the naive state. The finding that long- as well as short-latency components of unit activation increased after conditioning supported the hypothesis that generation of both long- and short latency blink CRs in normal animals may depend significantly on neural circuitry and mechanisms within the motor cortex. PMID- 1740692 TI - Increases in excitability of neurons of the motor cortex of cats after rapid acquisition of eye blink conditioning. AB - Measurements were made of resting potentials, input resistance, and excitability to intracellularly applied, depolarizing current pulses in neurons of the pericruciate cortex of conscious cats before and after acquisition of a rapidly conditioned eye blink reflex (CR). Neuronal excitability increased after conditioning, and an increased input resistance was found to be correlated with the increased level of excitability. No associated changes were found in resting potentials as a consequence of conditioning. When cells were divided into groups according to the latency of spike activity elicited by a click conditioned stimulus (CS) in relation to four separate excitatory EMG components of the compound blink CR, excitability increases were found in cells with increased spike activity at alpha 1 (8-40 msec), alpha 2 (40-72 msec), beta (72-112 msec), and gamma (112-160 msec) latencies after delivery of the CS. Also, the proportion of cells with high excitability (less than 0.7 nA required for spike elicitation) was increased at each latency period after conditioning. Increases in later components of spike discharge could also be found in the cells with increases in earlier components of discharge and increased excitability. The findings suggested that excitability increases facilitated a responsiveness to the CS that supported production of long- as well as short-latency components of the blink CR. Many of the changes in neuronal properties found after rapid eye blink conditioning, such as the increases in excitability and resistance and in the proportion of CS-excitable cells, resembled changes found earlier after acquisition of a slowly developing Pavlovian blink CR, using the same click CS and tap unconditioned stimulus without addition of a hypothalamic stimulus. The possibility should be considered that the (10-100 times) more rapidly acquired form of eye blink conditioning does not represent a different form of conditioning, but instead a change in the rate of conditioning supported by the more rapid production of increases in neural excitability. PMID- 1740693 TI - Transforming growth factor alpha, but not epidermal growth factor, promotes the survival of sensory neurons in vitro. AB - Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide that is structurally homologous to epidermal growth factor (EGF) and appears to bind to the same receptor in all systems tested previously. In the present study, TGF alpha was found to enhance survival and neurite outgrowth of cultured neonatal rat dorsal root ganglion (DRG) neurons in a dose-dependent manner. This effect was observed with TGF alpha concentrations as low as 17.8 pM. By contrast, EGF at concentrations up to 83 nM was ineffective. Moreover, EGF did not antagonize the TGF alpha survival-promoting effect unless present in large excess (500-fold the concentration for which TGF alpha is effective); even in this case, only partial antagonism was achieved. Survival of neurons from nodose, trigeminal, and sympathetic ganglia was not increased by TGF alpha. Both a subpopulation of DRG neurons and of macrophages in the cultures bound iodinated TGF alpha. This binding was inhibited by excess unlabeled TGF alpha but not EGF. Our data are consistent with the possibilities that the actions of TGF alpha on DRG neurons occur indirectly via unidentified neurotrophic molecules other than NGF as well as directly on the neurons themselves. Thus, TGF alpha, in contrast to EGF, may act as a survival or maintenance factor for a subset of rat sensory neurons. Mediation of this neurotrophic effect appears to occur via a new form of TGF alpha receptor. PMID- 1740694 TI - Cerebellar target neurons provide a stop signal for afferent neurite extension in vitro. AB - The contributions of cell-cell interactions to the establishment of specific patterns of innervation within target brain regions are not known. To provide an experimental analysis of the regulation of afferent axonal growth, we have developed an in vitro assay system, based on the developing mouse cerebellum, in which afferent axons from a brainstem source of mossy fiber afferents, the basilar pontine nuclei, were cocultured with astroglia or granule neurons purified from the cerebellum. In the absence of cells from the cerebellum, pontine explants produced axons that fasciculated and extended rapidly on a culture surface treated with poly-lysine or laminin. When pontine neurites grew onto cerebellar astroglial cells, outgrowth was more abundant than on substrates alone, suggesting that glial cells provide a positive signal for axon extension. Time-lapse video microscopy indicated that the rate of neurite extension increased from less than 50 microns/hr to more than 100 microns/hr when axonal growth cones moved from the culture substratum onto an astroglial-cell surface. Acceleration of neurite extension was also observed as pontine neurites grew onto other pontine neurites. By contrast, when pontine neurites grew on granule neurons, the appropriate targets of mossy fibers, the length of pontine neurites was greatly reduced. As growing axons terminated on granule neurons, the target cells appeared to provide a "stop-growing signal" for axon extension. The length of pontine neurites decreased with increasing granule neuron density. Two lines of evidence suggested that the stop signal was contact mediated. First, video microscopy showed that pontine growth cones stopped extending after contacting a granule neuron. Second, the length of afferent axons was not reduced when pontine neurites grew at a distance from granule neurons. Competition experiments where both astroglia and granule neurons were plated together suggested that the growth arrest signal provided by granule neurons could override the growth-promoting signal provided by astroglial cells. These results suggest that specific cell cell interactions regulate the growth of pontine afferent axons within their cerebellar target, with axoaxonal and axoglial interactions promoting axon extension and axon-target cell interactions interrupting axon extension. PMID- 1740695 TI - Transient calbindin-D28k-positive systems in the telencephalon: ganglionic eminence, developing striatum and cerebral cortex. AB - Calbindin-D28k (calbindin) is a member of the superfamily of calcium-binding proteins implicated in the regulation of intracellular calcium. In the mature brain, calbindin is widely expressed in neurons of the forebrain and the hindbrain, and in the telencephalon calbindin-like immunoreactivity is particularly strongly expressed by medium-sized neurons of the striatum and by certain other neurons in the cortex and subcortex. We have traced the development of calbindin expression in the forebrain of the rat, and report here that in addition to the steady development of these calbindin-positive neuronal systems, transient waves of calbindin expression occur in cells of the ventricular zones of the basal ganglia and cortex and in cells of the telencephalic regions derived from these ventricular zones including radial glia of the developing striatum. In the striatum and its ventricular zone (the ganglionic eminence, or GE) we identified four transient calbindin-positive systems in the perinatal period. First, calbindin-immunoreactive cells began to appear in the GE by embryonic day (E)18, and by E20 an extensive dorsal and lateral part of the GE was marked by dense calbindin-like immunoreactivity in the ventricular zone. This calbindin system peaked at postnatal day (P)0-P3 and disappeared by P15. Its presence suggests that the GE is divisible on a molecular basis into lateral and medial districts that may correspond to derivatives of the lateral and medial ventricular ridges. Second, a system of calbindin-positive processes appeared in the dorsal and lateral caudoputamen with temporal and spatial distributions matching the germinal zone system. Many of these processes could be traced from calbindin-positive cells in the ventricular zone of the GE, including processes stretching across the full width of the dorsal caudoputamen. Double-staining experiments demonstrated that these radial processes were Rat.401-positive, suggesting that they form a subset of radial glia in the developing telencephalon. These findings demonstrate that during development calbindin is expressed in glial as well as neural cells. They further suggest that the radial glia associated with the GE form heterogeneous populations, the transient calbindin-positive radial glia being associated with the lateral ridge of the GE and its derivatives. Third, a scattered population of calbindin-positive cells with morphologies different from the common medium-sized calbindin-immunoreactive neurons of the striatum appeared in the dorsal and lateral striatum from about E20 to P15. Some of these cells were close to the transient calbindin-positive radial processes in the same region, but others were not.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1740696 TI - Agreement states still chafing under NRC compatibility. PMID- 1740697 TI - Positron emission tomography using fluorine-18-fluorodeoxyglucose in malignant lymphoma: a comparison with proliferative activity. AB - To evaluate the relationship between PET using 18F-fluorodeoxyglucose (FDG) and pathological findings and to compare indices obtained by FDG-PET, FDG-PET was performed in 23 patients with untreated malignant lymphoma. Three indices obtained by FDG-PET, tumor-to-normal contrast ratio (TCR), distribution absorption ratio (DAR), k1k2/(k2 + k3), correlated with proliferative activity which was pathologically estimated both by mitotic count and by proportion of cells in all phases of the cell cycle. The relationship did not significantly change according to which of the three indices was chosen. FDG-PET, which shows the proliferative activity of tumors, is considered to be a useful method for managing tumors. PMID- 1740698 TI - Clinical applications of positron emission tomography in cancer: the good, the bad and the ugly. PMID- 1740699 TI - Quantitating tumor glucose metabolism with FDG and PET. PMID- 1740700 TI - Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum. AB - In a retrospective study of a series of 30 adult patients during restaging of Hodgkin's disease after therapy, computed tomography (CT) and biopsy results were correlated with 67Ga SPECT in order to determine the value of SPECT imaging in monitoring recurrent mediastinal Hodgkin's disease. SPECT had an overall accuracy of 93% (28/30) and correctly identified active disease in 24 of 25, 96% of histopathologically proven recurrent Hodgkin's disease. Thus in this post-therapy setting, we have confirmed the high sensitivity of 67GA SPECT scans in patients selected for biopsy. Gallium-67 may prove particularly useful in detecting residual disease activity in patients in whom biopsy was positive but the interpretations of the CT scans were uncertain in regard to presence of tumors [8/30 (27%)]. In this group of patients, we found SPECT particularly helpful. A larger prospective series is under way to assess this possibility. PMID- 1740701 TI - Bone scintigraphy in preschool children with lower extremity pain of unknown origin. AB - Small children often cannot describe the location of bone pain for parents or physicians. Bone scans were performed in 56 children under five years of age with lower extremity pain and/or gait abnormalities of unknown etiology. Patients with fever, and those known to have infection, child abuse, malignancy, and/or radiographic abnormalities were excluded. Thirty patients had abnormal bone scans. Abnormalities included evidence of hip synovitis (4), femoral head avascularity (2), various proximal femoral abnormalities (3), knee synovitis (3), toddler's fracture (1), various tibial or fibular abnormalities (4), and various abnormalities of the tarsal bones (16). Tarsal bone abnormalities included four with abnormal calcaneal uptake and nine with abnormal uptake in or adjacent to the cuboid bone. Correlative imaging studies were available for 26 sites, and focal bone findings were noted at only five locations. Tarsal bone abnormalities accounted for over half of the scintigraphic abnormalities in these preschool children with gait abnormalities. Abnormal uptake in/or adjacent to the cuboid bone was common and probably represented stress injury. PMID- 1740702 TI - Effects of dipyridamole infusion on human renal function observed using technetium-99m-DTPA. AB - Our observation that a prolonged dipyridamole infusion reduced or eliminated blood clearance of Gd-DTPA in dogs led us to investigate if dipyridamole, infused intravenously at rates comparable to those used in thallium myocardial perfusion tests, would alter renal filtration in humans. Renal filtration was assessed using a bolus injection of 10 mCi of 99mTc-DTPA in five males (19-63 yr old) with normal serum urea and creatinine. Twenty minutes following the bolus injection a 10-min intravenous infusion of either dipyridamole (0.14 mg/kg/min) or saline sham was given. Four to 10 min following the start of the dipyridamole infusion, a paradoxical rise in counts in the kidney region of interest was observed and persisted for 10 to 27 min. During this time, a 13% to 52% (mean +/- s.d., 40% +/ 16%, p less than 0.007) reduction in the exponential slope defining the clearance of counts from the cardiac region of interest occurred (implying a reduction of glomerular filtration rate), mean heart rate increased 27 +/- 5 bpm, p less than 0.002 and mean diastolic pressure decreased 12.9 +/- 6.4 mmHg, p less than 0.028. This finding indicates that renal clearance of tracers such as thallium or contrast agents such as Gd-DTPA is reduced during dipyridamole infusion. PMID- 1740703 TI - The frequency of asymptomatic and electrically silent exercise-induced regional myocardial ischemia during first-pass radionuclide angiography with upright bicycle ergometry. AB - The presence of asymptomatic (silent) myocardial ischemia during provocative testing may limit the detection of ischemic heart disease, unless sensitive indicators of ischemia are utilized. Exercise ventricular function studies are well suited for ischemia detection since segmental dysfunction is an early pathophysiologic event in the ischemic cascade. In this study, we examined the rest and stress first-pass radionuclide angiographic studies of 104 patients with coronary artery disease and exercise-induced regional wall motion abnormalities. Asymptomatic ischemia was observed in 83 patients, while only 21 patients were symptomatic. Clinical variables were not different between the two groups, except for a higher frequency of a prior anginal history in the symptomatic group. The peak heart rate and pressure-rate product were significantly higher in the silent ischemia group, as these patients are not limited by symptoms. Wall motion scores, resting and exercise ejection fractions were similar in the two groups. The frequency of an ischemic electrocardiographic ST-segment response was low, and was not significantly different between groups. These data indicate that electrically and symptomatically silent myocardial ischemia are frequent occurrences with upright bicycle ergometry. Without adjunctive cardiac imaging, this mode of exercise may not be appropriate for the evaluation of ischemic heart disease. PMID- 1740704 TI - Diagnostic value of technetium-99m radionuclide angiography for detecting thrombosis in left atrial appendage. AB - In mitral valve disease, it is important to know whether thrombi are present in the left atrium when deciding upon a course of treatment. The left atrial thrombus usually locates in the left atrial appendage. In most cases of mitral valve disease, the left atrial appendage is clearly demonstrated by radionuclide angiography using 99mTc-labeled red blood cells and it can be speculated that the cases in which left atrial appendage are not demonstrated by RNA have left atrial thrombi. On the basis of this hypothesis, the diagnostic accuracy of radionuclide angiography to detect left atrial thrombi was evaluated retrospectively in 60 patients with mitral valve disease who had undergone surgery. The sensitivity of first-pass and equilibrium radionuclide angiography to detect left atrial thrombi was 83% and 67%, the specificity 79% and 54%, and the accuracy 80% and 57%, respectively. Although there were two false-negative cases in which the left atrial thrombi did not locate in the appendage and 10 false-positive cases in which left atrial appendages were not dilated, the negative predictive value was so high that a clearly demonstrated left atrial appendage can be translated into the absence of left atrial thrombi. PMID- 1740705 TI - Radiation-induced inhibition of tumor growth as monitored by PET using L-[1 11C]tyrosine and fluorine-18-fluorodeoxyglucose. AB - The potential use of PET to monitor radiotherapeutic effects on tumors has been evaluated with L-[1-11C]tyrosine and 18FDG. Single x-ray doses of 10, 30, or 50 Gy have been applied to rhabdomyosarcoma tumors growing in the flank of rats. Dose-dependent reductions of tracer uptake were registered by PET 4 and 12 days after treatment. These later effects on tracer uptake appeared to correlate with changes in tumor volume. Therefore, PET using L-[1-11C]tyrosine and 18FDG is suitable to monitor kinetics of tumor growth and tumor regression after radiotherapy. Direct effect on tracer uptake was not observed within 8 hr after irradiation. This indicates that, using PET, early predictions on the outcome of radiotherapy are not possible. When combining a radiation treatment with hyperthermia, radiation-induced inhibition of tumor growth was clearly enhanced. Tracer uptake remained at the pretreatment value, possibly due to invasion of host cells. From these experiments, it can be concluded that it is difficult to monitor a combined treatment of radiation and hyperthermia by PET. PMID- 1740706 TI - Dosimetry at the cellular level of Kupffer cells after technetium-99m-sulphur colloid injection. AB - The radiation dose to Kupffer cells was estimated at the cellular level after intravenous injection of 99mTc labeled sulphur colloids in rats. The results were then compared with those obtained using macroscopic dosimetry. From the microscopy appearance observed using a "track" microautoradiographic method (MAR), it was shown that only 0.2% of the Kupffer cells were actually involved in the pinocytosis of radioactive colloids. For each electronic emission from 99mTc (Auger and internal conversion), the fraction of the emitted energy actually absorbed within the Kupffer cell was calculated using the values provided by Berger. About 15% of the total energy emitted by electrons was absorbed in 0.2% of the Kupffer cells. If these results are extrapolated to humans, the dose absorbed by the labeled cells can be estimated to be between 0.5 and 0.9 Gy/MBq. This represents about 15,000 times the average electron dose to the liver as estimated from macrodosimetric methods. In cases such as this one where an important distribution heterogeneity is expected, dosimetric estimations at a cellular level may be particularly useful. PMID- 1740707 TI - Does nonuniformity of dose have implications for radiation protection? PMID- 1740708 TI - Biodistribution and kinetics of radiolabeled proteins in rats with focal infection. AB - The purpose of this study was to evaluate the role of both protein and radionuclide in the accumulation of 111In-labeled human immunoglobulin G (IgG) in infectious foci. In rats with a calf muscle infection, biodistribution was determined 2, 6, 24, and 48 hr after injection of a radiopharmaceutical. For IgG, human serum albumin (HSA) and human immunoglobulin A (IgA), all labeled with 111In, target-to-background (T/B) ratios were similar throughout the study. However, absolute abscess uptake of 111In-IgA was significantly lower. For IgG labeled with 111In, 123I, or 99mTc, similar T/B ratios were found up to 24 hr. After 48 hr, the T/B ratio of 111In-IgG was significantly higher than the T/B ratio of 123I-IgG. The absolute abscess uptake of 111In-IgG was higher than that of 99mTc-IgG at 24 hr and 123I-IgG at 48 hr. In conclusion, the radionuclide appears to be of major importance in the accumulation of radiolabeled proteins in infectious foci. Protein mainly influences blood clearance and distribution in organs. The Fc-gamma receptor is not crucial for accumulation in infectious foci. PMID- 1740709 TI - Targeted proteins for diagnostic imaging: does chemistry make a difference? AB - The Oyen et al. study is valuable in that it systematically evaluates several of the factors involved in radiolabeled protein uptake and retention in infectious foci. The role of particular proteins and their receptor specific interactions seems to be inconsequential in agreement with the findings of other. However, the role of the radiolabel was shown to be important and significant differences were delineated from comparisons of the radionuclides and their associated chemistries. The conclusion implicating radionuclide chemistry and associated linkages underscores the need to optimize the attachment and labeling chemical modifications of protein carriers. Evaluation criteria should include serum stability, determination and assessment of the effect of molar substitution ratio, and potential for improving blood clearance without reducing the target-to non-target ratio. Important areas for future study include characterization of radioactive metabolites and the design and synthesis of new ligands which direct the disposition of metabolites reducing retention in normal organs or accelerating renal excretion. Additionally, intracellular processing of radiolabel, compartmental distribution and strategies for augmenting internalization and retention within the target cell merit detailed exploration. For each radionuclide of interest, 111In, radioiodines, 99mTc and others, improved chemical moieties exist for controlling radiolabel fate. When carrying out mechanistic and evaluative studies, clear-cut conclusions will only be reached when defined and controlled chemistry is used. Having established a "gold standard," simplifications in radiolabeling and other chemical refinements can then be pursued with a quantitative understanding of the trade-offs in targeting agent performance versus other considerations such as cost reduction, simplicity, and convenience. PMID- 1740710 TI - Polymeric microspheres for radionuclide synovectomy containing neutron-activated holmium-166. AB - Poly-L-lactic acid (PLA) microspheres containing neutron-activated 166Ho were investigated as potential agents for radionuclide synovectomy. Stable 165Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 microns (range 2-13 microns) containing 25.4% 165Ho-AcAc (9.1% 165Ho) were irradiated in a high neutron flux to produce 31.1-36.0 mCi 166Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 +/- 0.01% of the 166Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257-591 microCi 166Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed 166Ho retention in the joint space after 120 hr of 97.7% +/- 0.8% and 98.2% +/- 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the 166Ho make them attractive agents for radionuclide synovectomy. PMID- 1740711 TI - Experimental study on radioactive pathways of hypodermically injected technetium 99m. AB - The objective of this study was to investigate the biological substrate of radioactive pathways of migration of hypodermically injected 99mTc into points of low electrical resistance. Sixteen anesthetized adult male beagles were used. Control and test points were defined by comparing their electrical resistance to that of the pinna. Seventy-three experiments of three different types were performed: (1) separate hypodermic injections of [99mTc] sodium pertechnetate, 201Tl-chloride, 131INa and 99mTc-rhenium sulfide into control and test points; (2) simultaneous injections of [99mTc]sodium pertechnetate and 201Tl chloride into control and test points; and (3) intravascular injections of 99mTcO4 into blood vessels underlying test points. Only the hypodermic injection of 99mTc into points of low electrical resistance gave rise to a specific radioactive pathway characterized by rapid and longitudinal migration, clearly independent of background activity. The specific radioactive pathway detected is not the result of diffusion of the radiotracer through nerves, veins or lymphatic vessels, but its trajectory coincides with that described for one of the acupuncture meridians in the dog. PMID- 1740712 TI - Anatomic divisions. PMID- 1740713 TI - Synthesis, rodent biodistribution, dosimetry, metabolism, and monkey images of carbon-11-labeled (+)-2 alpha-tropanyl benzilate: a central muscarinic receptor imaging agent. AB - Muscarinic cholinergic receptors (mAChR) are abundant in the brain, and the mAChR system mediates many aspects of brain function. There is evidence of alterations in muscarinic binding in degenerative brain disorders. A muscarinic receptor radioligand, carbon-11-(+)-2 alpha-tropanyl benzilate ([11C]TRB), has been prepared through N-[11C]methylation of N-desmethyl TRB, and evaluated in rodents and primates. Full body biodistribution in rats has been determined and the expected human dosimetry calculated. Comparisons with [11C]scopolamine in rats showed 2-6 times greater brain uptake of [11C] TRB. Highly specific and saturable binding of [11C]TRB in the striatum and cortex was demonstrated by greater than 85% blockade of uptake following QNB or scopolamine pretreatment. Striatum/cerebellum ratios in mice at 60 min exceeded 12.6. TLC analysis of rat tissues showed the absence of 11C-metabolites in brain and heart, and a rapid solid phase C-18 Sep-Pak method found that unmetabolized plasma [11C]TRB in monkeys fell from 81% at 5 min to 48% at 80 min. Finally, brains of living primates have been imaged using PET and [11C]TRB; regional localization was consistent with muscarinic receptor distribution. These results represent intermediate steps in the development of [11C]TRB for quantification of central muscarinic receptors in man. PMID- 1740714 TI - Identification and differentiation of congenital gallbladder abnormality by quantitative technetium-99m IDA cholescintigraphy. AB - Failure to visualize the gallbladder in its usual location along the right inferior hepatic border suggests many possibilities including acute cholecystitis. The case described here reveals the importance of proper protocol for hepatobiliary imaging with 99mTC-IDA agents, the necessity of quantification of function as an integral part of imaging to enable proper differential diagnosis. A case of bilobed gallbladder presenting as a Valentine heart in an unusual location in the liver is described. The measurement of the CCK-8 induced gallbladder ejection fraction for each lobe facilitated proper diagnosis. PMID- 1740715 TI - Radiographic and neuro-SPECT imaging in an immature third ventricle teratoma: case report. AB - We report a case of an immature teratoma of the third ventricle, which was preoperatively thought to be a choroid plexus papilloma. The diagnosis was made by biopsy since the radiographic (CT, MRI), angiographic and scintigraphic findings ([99mTc]pertechnetate, 99mTc-DTPA, 99mTc-HMPAO brain SPECT) were nonspecific. Disruption of the blood-brain barrier is the mechanism for radionuclidic and contrast tumoral uptake and is demonstrated by marked contrast enhancement on CT and focal concentration on [99mTc]pertechnetate and 99mTc-DTPA images. No suppression of [99mTc]pertechnetate tumor uptake was observed following the administration of potassium perchlorate. Increased concentration of tumor protein is suggested by the increased signal on the T1-weighted magnetic resonance images and high [99mTc]pertechnetate uptake. The tumor's detection on the 99mTc-HMPAO brain SPECT was due to its intraventricular location. A number of potential mechanisms for brain tumor localization of 99mTc-HMPAO are discussed. PMID- 1740716 TI - Comparison of independent aura, ictal and interictal cerebral perfusion. AB - Technetium-HMPAO cerebral SPECT was performed interictally, immediately after an independent aura and ictally in a patient with complex partial seizures. Interictally there was a left inferior frontoparietal region of decreased perfusion. Ictally there were a number of foci of increased perfusion. The aura study showed focal hyperperfusion in the left frontal region and decreased perfusion in the adjacent cortex posteriorly, suggesting a zone of suppression. This may be the cause or effect of the nonprogression of the aura. The case raises the possibility that cerebral perfusion studies performed immediately after independent auras may localize seizure foci if ictal studies are nonfocal. PMID- 1740717 TI - Application of a continuous ventricular function monitor with miniature cadmium telluride detector to patients with coronary artery bypass grafting. AB - A continuous ventricular function monitor with a miniature cadmium telluride detector was evaluated and applied to patients with coronary bypass surgery (CABG). Ejection fraction (EF) at rest and change in EF from rest to exercise and postexercise (Y) measured with the device correlated with that of the gamma camera (X) (Y = 0.86x + 6.8(%), r = 0.87, n = 110, p less than 0.001, and Y = 0.96x + 0.4(%), r = 0.90, n = 37, p less than 0.001 respectively). Left ventricular function during and after supine ergometer exercise was monitored in 54 patients before and after CABG. The EF change from baseline to peak exercise improved from -5.9% +/- 8.9% before CABG to 7.2% +/- 7.9% after CABG (p less than 0.001). In all patients but two, a rapid EF increase just after exercise over baseline EF was observed. This EF "overshoot" during recovery increased from 11.5% +/- 6.5% to 16.4% +/- 6.0% (p less than 0.001) after CABG. The time from the cessation of exercise to EF overshoot decreased from 153 +/- 80 sec to 76 +/- 49 sec (p less than 0.001) after CABG. The continuous ventricular function monitor with a miniature cadmium telluride detector is able to measure EF reliably. Following successful aortocoronary bypass, EF response during exercise improved and the EF overshoot in the recovery phase became faster and higher. PMID- 1740718 TI - Nuclear probes in cardiology. PMID- 1740719 TI - An evaluation of maximum likelihood-expectation maximization reconstruction for SPECT by ROC analysis. AB - A ROC study was performed in order to evaluate whether the maximum likelihood expectation maximization (ML-EM) reconstruction algorithm improves diagnostic performance compared to the conventional filtered backprojection method in SPECT. Several implementations of the algorithm were tested including 25 and 50 iteration stopping points, with and without nonuniform attenuation compensation, and with and without Metz filtering. Filtered backprojection was with Metz filter and without attenuation compensation. The test data were computer simulated to model cardiac 201Tl SPECT. The data incorporated the effects of nonuniform attenuation, distance-dependent collimator response, and scatter. Patient CT images provided realistic anatomy and attenuation information for the data simulation. Four observers each viewed 120 images for each of the reconstruction methods. Lesion detectability with ML-EM increased with Metz filtering and decreased with nonuniform attenuation compensation. The best MIL-EM implementation, 50 iterations with Metz filtering and without attenuation compensation, was not statistically better than filtered backprojection. PMID- 1740720 TI - Three-dimensional presentation of the Fourier amplitude and phase: a fast display method for gated cardiac blood-pool SPECT. AB - The routine clinical use of gated SPECT is inhibited by sophisticated, time consuming processing techniques. The present paper describes a new technique for the simultaneous three-dimensional presentation of the amplitude and phase of the first Fourier harmonics, with the aim of obtaining detailed information about the ventricular motion in a relatively short time, from each angle of view of three dimensional space. The method is simple and robust, and processing is automatic. It does not need carefully elaborated techniques for surface determination, because the cardiac surface is merely used as a reference skeleton onto which the functional information of amplitude and phase is mapped. The Fourier analysis before reconstruction results in running times shorter than 15 min and may further open the way for the routine use of gated SPECT. PMID- 1740721 TI - The importance of a delayed scan in thallium imaging. PMID- 1740722 TI - Incorrect naming of a carbon-11-labeled reagent. PMID- 1740723 TI - Providing support for preceptors in a community hospital. AB - An inexpensive support system for preceptors centered around monthly inservice programs is described. This approach has resulted in improved documentation of the preceptee's progress and greater consistency in how preceptors implement their role. In addition, preceptors believe their concerns are heard. During a nursing shortage, many hospitals may benefit from implementing a similar support system for their preceptors. PMID- 1740724 TI - Partnership between education and service for psychiatric staff education. AB - Economic restraints and limited resources have made partnerships between nursing service and nursing education a growing imperative. Although economics are a major consideration in establishing partnerships, there can be other professional advantages to the institution and the community. PMID- 1740725 TI - A study of nurses who completed a hospital-based reentry program. AB - This article describes a survey of nurses who completed a reentry program. The study resulted in information about demographics, job history, career development, and career satisfaction. Findings reveal that the reentry program was successful in assisting inactive nurses to return to the work force. PMID- 1740726 TI - A model combining centralized and decentralized staff development. AB - Traditionally, most nursing staff development departments are either decentralized or centralized. This article presents the advantages and disadvantages of each of these organizational systems and describes a model used at the National Institutes of Health that combines elements of both. Strategies to control for the disadvantages are outlined. This organizational structure may enable staff development educators to better meet the educational needs of nurses in today's health care settings. PMID- 1740727 TI - A comparison of four nursing documentation systems. AB - Nurses must be able to keep charts effectively and efficiently while providing high-quality care. Often, nurse educators are responsible for finding a workable system for a particular institution. This article reviews four nursing documentation systems that can be used in a variety of health care settings: Problem Centered, PIE (Problem Intervention Evaluation), Focus, and Charting by Exception. PMID- 1740728 TI - Implementing a neonatal resuscitation program. AB - This experience with the implementation of the neonatal resuscitation program has been positive. Collaborative planning between nursing staff education and nursing management has resulted in an efficient and rewarding certification process. PMID- 1740729 TI - Mandatory nurse assistant training for more competent caregivers. PMID- 1740730 TI - Designing quality brochures. AB - Many formulas may be used to create a brochure. The main goal is to entice people to read the material. Designing and preparing brochures in house offers a great deal of flexibility and is generally less expensive than having them designed outside. Brochures can be produced very creatively, and they give the education department yet another opportunity to develop professionally. PMID- 1740731 TI - Getting started--overview of the educational design series. PMID- 1740732 TI - Knowledge retention and clinical application after continuing education. AB - The authors investigate the knowledge retention and clinical application of physical assessment skills by nurses who participated in a required continuing education workshop. Tools were developed to measure the specific application of workshop concepts. Results support the underlying objectives of nursing staff development, which are to increase knowledge and improve skills. PMID- 1740733 TI - The early effects of joint immobilization on medial collateral ligament healing in an ACL-deficient knee: a gross anatomic and biomechanical investigation in the adult rabbit model. AB - In this study, the short-term effects of immobilization on joint damage and medial collateral ligament (MCL) healing were investigated in unstable, anterior cruciate ligament (ACL)-deficient knees in rabbits. Forty-six 12-month-old female New Zealand white rabbits were separated into three groups. Animals from each group had surgery on their right knees: group I, sham controls (n = 9); group II, complete transection of the ACL and removal of a 4 mm segment (gap injury) of MCL midsubstance with no immobilization of the limb (n = 19); and group III, same injuries to the ACL and MCL (as group II) but with immobilization of the limb (n = 18). No surgical repair of disrupted ligaments was performed. Left knees served as unoperated contralateral controls. All animals were allowed unrestricted cage activity until sacrifice in subgroups at 3, 6, and 14 weeks of healing when biomechanical properties of all MCLs were measured. All knee joints were systematically examined for gross evidence of damage to articular cartilage, menisci, and periarticular soft tissues. To monitor relative in vivo loads on injured limbs during healing, hindlimb weight bearing was assessed at biweekly intervals. Results indicated that animals in both groups II and III bore relatively lower loads (compared to preinjury values) on their injured hindlimbs. Mechanical testing of MCLs showed only minor changes in sham controls, while group II and III healing MCLs demonstrated significantly lower force and stress at MCL complex failure compared to contralateral controls. In specific comparisons of group III to group II animals, we noted that immobilization prevented joint damage over the early intervals studied. In addition, immobilization resulted in MCL laxity similar to contralateral control values but inhibited development of structural strength and stiffness in healing MCLs. These results suggest that in the rabbit, short-term immobilization of an ACL-deficient knee offers some advantages to the joint and to certain low load behaviors of the healing MCL, but it also results in a smaller quantity of scar tissue that is less able to resist higher loads. Longer-term studies involving remobilization are necessary before the effects of brief immobilization on joint damage and MCL healing in this ACL-deficient model can be fully defined. PMID- 1740734 TI - Strain in the anteromedial bundle of the anterior cruciate ligament under combination loading. AB - Strain within the anteromedial bundle (AMB) of the anterior cruciate ligament (ACL) was measured in 13 human knee specimens in order to determine the combination of external loads most likely to cause injury. Using a load application system that allowed 5 df with the flexion angle being fixed, pure loads of anterior/posterior force, medial/lateral force, varus/valgus torque, and internal/external axial torque were applied at three flexion angles: 0 degrees, 15 degrees, 30 degrees. Combined loads were applied in pairs at two flexion angles: 0 degrees and 30 degrees. Liquid mercury strain gauges were used to measure strain in the ACL. Anterior tibial force was the primary determinant of strain in the anteromedial bundle. This strain was significantly larger at 30 degrees flexion than at 0 degrees. The strain sensitivity of the AMB to medial force was approximately one-half that to pure anterior force. The effect of anterior and medial forces was additive when applied in combination. Neither pure axial torque nor pure varus/valgus torque was observed to strain significantly the AMB at any of the flexion angles investigated. However, valgus torque in combination with anterior force resulted in a significantly larger strain than pure anterior force. Internal axial torque in combination with anterior force also resulted in a larger strain than pure anterior force. PMID- 1740735 TI - Effect of tension and placement of a prosthetic anterior cruciate ligament on the anteroposterior laxity of the knee. AB - We wished to determine the optimal tension required to restore normal joint laxity to anterior cruciate ligament (ACL)-deficient knees using a braided polyethylene ACL prosthesis (PACL). In 10 cadaveric specimens, we measured the anteroposterior (AP) laxity of the intact knee at 10 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. The ACL was then removed and replaced with the PACL using tunnel-tunnel (T-T) and "over-the-top" (OTT) placement techniques. In both positions, the PACL was initially tensioned to 0, 9, 18, and 27 N with the knee flexed to 30 degrees. AP joint laxity was then measured at each flexion angle. With an increase in initial tension, there was a corresponding decrease in AP laxity. At 30 degrees and 90 degrees of flexion, AP laxity was not significantly different from normal using T-T placement and an initial tension of 0 N. At 90 degrees of flexion, AP laxity was not significantly different from normal using OTT placement at 0 or 9 N of initial tension. For both positions, all other tension levels and flexion angles constrained AP laxity. No laxity differences were detected between the OTT and T-T positions at any flexion angle. The variability in AP laxity of the T-T position was significantly greater than OTT. With a 150-N anterior shear force applied to the proximal tibia, the maximum tensions developed in the PACL were not significantly different between the two positions except at 90 degrees. The results suggest that implantation of the PACL is best performed using OTT positioning with an initial tension of 0 N applied at 30 degrees of knee flexion. PMID- 1740736 TI - Tensile properties of the inferior glenohumeral ligament. AB - The tensile properties of the inferior glenohumeral ligament have been determined in 16 freshly frozen cadaver shoulders. The inferior glenohumeral ligament was divided into three anatomical regions: a superior band, an anterior axillary pouch, and a posterior axillary pouch. This yielded 48 bone-ligament-bone specimens, which were tested to failure in uniaxial tension. The superior band was consistently the thickest region, averaging 2.79 mm. The thickness of the inferior glenohumeral ligament decreased from antero-superiorly to postero inferiorly. The resting length of all three anatomical regions was not statistically different. Total specimen strain to failure for all bone-ligament bone specimens averaged 27%. Variations occurred between the three regions, with the anterior pouch specimens failing at a higher strain (34%) than those from the superior band (24%) or the posterior pouch (23%). Strain to failure for the ligament midsubstance (11%) was found to be significantly less than that for the entire specimen (27%). Thus, larger strain must occur near the insertion sites of the inferior glenohumeral ligament. Stress at failure was found to be nearly identical for the three regions of the ligament, averaging 5.5 MPa. These values are lower than those reported for other soft tissues, such as the anterior cruciate ligament and patellar tendon. The anterior pouch was found to be less stiff than the other two regions, perhaps suggesting that it is composed of more highly crimped collagen fibers. Three failure sites were seen for the inferior glenohumeral ligament: the glenoid insertion (40%), the ligament substance (35%), and the humeral insertion (25%). In addition, significant capsular stretching occurred before failure, regardless of the failure mode. PMID- 1740737 TI - Biochemically discrete zones of canine flexor tendon: evaluation of properties with a new photographic method. AB - We describe a photographic method that we have found useful for studying small strain fields within a larger zone of interest. We have used this method to document differences in material properties which correlate with zones of different biochemical makeup in the canine flexor digitorum profundus tendon. This method may be useful in analysis of experimental injury and wound healing in this model and may have application in evaluating material properties of soft tissue in other models as well. PMID- 1740738 TI - Physicochemical properties of the aging and diabetic sand rat intervertebral disc. AB - Hydration, fixed charge density, (FCD) and hydration under various osmotic pressures were compared in young, old, and young diabetic sand rats. This rat is a desert animal that may develop diabetes when fed a regular diet; it is also known to have radiographic and histologic evidence of intervertebral disc (IVD) disease. Forty-five rats and 180 IVD were used in this study; they were divided into three equal groups: young healthy, old healthy, and young diabetics. IVD, cancellous bone, and muscle were sampled from distal lumbar spines. The young diabetic rats (YD) were considerably heavier than the age-matched controls, had higher insulin and glucose levels, and all YD had cataracts. The discs of the young diabetic animals demonstrated decreased hydration, FCD and ability to resist compression under osmotic pressures as compared with the young and healthy discs and were more similar to the discs from old rats. The IVD is the most affected musculoskeletal connective tissue in sand rats with aging and diabetes. The aged and diabetic discs in the sand rat demonstrated changes similar to human changes with regard to lower hydration, FCD, and ability to resist osmotic pressure. Therefore, the sand rat may be a suitable animal model for studying the pathogenesis of disc degeneration. PMID- 1740739 TI - Spinal mobility and posture in 8- to 16-year-old children. AB - Spinal mobility and posture were measured in 294 8-16-year-old boys and girls, divided into five age groups. The upper thoracic sagittal alignment was more vertical among girls, but the postural curves showed no significant age-related differences for either sex. Among both boys and girls thoracic extension, lateral flexion, and rotation decreased significantly between the ages of 12 and 13, but with the exception of extension they returned to the previous level by age 16. Girls were significantly different from boys at 13 years of age. In the thoracic spine, girls had less kyphosis, and were stiffer in forward and lateral flexion, with more rotation to the right than to the left. In the lumbar spine, lateral flexion increased after the age of 10 in both sexes. Between the ages of 8 and 14 lumbar lateral flexion was significantly greater among girls than among boys, whereas extension and rotation was greater only at the ages of 8 and 10 years. With increasing age, a shift from left to right dominance in lumbar lateral flexion was found in girls only. PMID- 1740740 TI - Trunk positioning accuracy in children 7-18 years old. AB - Trunk proprioception was measured in 253 healthy children 7-18 years of age using infrared markers placed on the back of the head and on the skin over the T1, T8, and S1 spinous processes. The children were tested for their accuracy in sensing return of the head and trunk to a centered, neutral position in the frontal plane. Whole-body sway was also quantified during 10 s of relaxed standing by measuring mean amplitudes of trunk marker and foot center of pressure (CP) movements. The results show that trunk positioning accuracy improved significantly with age (p = 0.000). Subjects could position their trunk in the frontal plane to within a mean (+/- SD) of 2.5 (+/- 1.1) and 0.9 (+/- 0.6) degrees of the neutral position at ages 7 and 18 years, respectively. No statistically significant gender differences were found. At every age trunk positioning accuracy was diminished in the presence of a continuous external trunk moment (equivalent to 0.01 x body weight x height), although not significantly so. Neither mean trunk sway nor CP amplitudes were significantly correlated with age or sex. The overall results suggest that spine decompensation is only abnormal when it exceeds 20 mm in healthy children and adolescents. PMID- 1740741 TI - Pattern analysis of electromyographic linear envelopes exhibited by subjects with uninjured and injured knees during free and fast speed walking. AB - We wished to determine whether anterior cruciate ligament (ACL) injury caused changes in patterns of activity of individual or groups of muscles that control the knee joint. The electromyographic (EMG) patterns of six muscles in 26 individuals with uninjured knees and 20 individuals with ruptured ACL were studied during free and fast speed walking. A previously developed clustering technique was used for analysis. This technique involves making the Fourier transform of the average linear envelope (LE) of each muscle for each subject and using the amplitude and phase angles of the lower frequency harmonics as features to describe a pattern. These features are then grouped to subdivide the population of EMG patterns into different types. The results of analyses on single muscles showed that there exists a typical or "normal" pattern for each muscle which most uninjured and some injured subjects exhibit as well as several atypical patterns which mostly injured subjects exhibit, and that the atypical patterns are much more evident at fast walking speed. The characteristics of atypical patterns with respect to normal include time shifts in the peak of major phases of activity, the absence of a second phase of activity, and the existence of additional phases of activity. Synergy analysis showed that if one muscle has an atypical pattern, then several do; i.e., ACL injury induces major changes in the control strategy of the knee. The implications are that for rehabilitation programs one must focus on the training and strengthening of more than one muscle, and that for reconstructive procedures the changes in mechanics of the joint can possibly induce a significant change in its control strategy. PMID- 1740742 TI - Mechanical properties of microcallus in human cancellous bone. AB - Until now, the mechanical properties of the microcalluses that form in human cancellous bone have been unexplained. We measured the microhardnesses of microcalluses in cancellous bone, of the trabeculae within the microcalluses, of the trabeculae adjacent to microcalluses, and of trabeculae lacking microcalluses in a human tibia and femur. We observed no important differences between materials at the four different sites. Because the microhardness of bone is very closely related to its stiffness, this finding indicates that microcalluses are likely to stiffen the trabeculae in which they are formed, even though they may surround unhealed fractures of the cancellous trabeculae. PMID- 1740743 TI - Comparison of asymmetrical and symmetrical pulse waveforms in electromagnetic stimulation. AB - Pulsing electromagnetic field (PEMF) stimulation is a noninvasive therapeutic modality that has been successfully used to stimulate healing of surgically resistant human bone fracture nonunions. Asymmetry of the stimulus pulse waveform was thought to be necessary for therapeutic effectiveness, but asymmetrical pulses require significant electrical energy that constrains clinical delivery systems to suboptimal designs. Development of low-energy consuming stimuli will enable clinical device improvements and may provide additional information about the interaction of electromagnetic fields with tissues. The objectives of this study were (a) to determine if asymmetry of the stimulus pulse waveform is needed for efficacy and (b) to determine if symmetrical pulse waveform stimuli also can produce a beneficial therapeutic response. The rabbit fibular osteotomy model was used to answer these questions and to identify which components of the clinically used asymmetrical PEMF produce the therapeutic response. The results suggest that asymmetry is not necessary and that a narrow pulse width, symmetrical square wave signal can also stimulate stiffness increases in this model. The data also suggest that the high-amplitude, narrow-pulse portion of the asymmetrical PEMF is the principal component of the signal pulse that is responsible for the clinical therapeutic effect. PMID- 1740744 TI - The microstructural tensile properties and biochemical composition of the bovine distal femoral growth plate. AB - The tensile properties of distal femoral growth plates from 12-month-old cows were determined on uniformly prepared straight bone-growth plate-bone specimens (7 x 7 mm2 in cross-section) from predetermined anatomical sites on the physis. Each specimen was distracted to failure using a computer-controlled servo hydraulic testing machine at a strain rate of 0.004 s-1. It was found that the exponential constitutive law, using finite deformation formulation for strain, provides an excellent description of the stress-strain behavior of all the specimens up to the point of failure. The ultimate stress and both tangent moduli (i.e., the toe region tangent modulus and the tangent modulus calculated at 75% of ultimate strain) varied with anatomical site. The anterior region was the strongest, followed by the posterior/lateral. The anterior and posterior/lateral regions were also the stiffest, whereas the posterior/medial and center regions were the weakest and most compliant. The bone-growth plate-bone specimen exhibited a low ultimate strain (13.8% +/- 6%) that did not vary significantly throughout the growth plate. This result suggests that disruption of the physis may occur in vivo even at the lower distractions currently recommended for the clinical chondrodiatasis procedure for leg lengthening. The biochemical composition of the growth plate in the anatomical regions correlated well with the tensile properties. There was a greater collagen content in the regions that were the stiffest and strongest. The gross morphology of the growth plate of the bovine distal femur is also described in this study. There is a regular pattern to the undulations of the physis at several dimensional levels. Histologic findings showed that orientation of the hypertrophic cell columns and transphyseal septa are aligned nearly parallel to the longitudinal axis of the diaphyseal shaft. This column orientation is not affected by the undulation of the primary contour of the physis, which at certain locations may be inclined as much as 60 degrees relative to the diaphyseal axis. The orientation of the hypertrophic cell columns appears to be one of the dominant microstructural features influencing the tensile behavior of the bone-growth plate-bone specimens. PMID- 1740745 TI - Influence of continuous infusion of interleukin-1 alpha on the core protein and the core protein fragments of the small proteoglycan decorin in cartilage. AB - Decorin, a collagen-binding small proteoglycan, is considered to have a specific function in the organization or stability of the collagen network. Therefore, alteration of its molecular properties may be of pathophysiological relevance during the development of cartilage damage. It is shown here that normal cartilage from rabbit knee-joint contains glycosaminoglycan chain-bearing core protein fragments of 39, 23, and 18 kDa, each one amounting to approximately 5-6% of the intact decorin core protein. Continuous infusion of human recombinant interleukin-1 alpha for 14 days (200 ng/day) into a knee-joint led in condylar cartilage to a reduction in the amount of intact core protein from 2 micrograms/mg wet tissue to about 1.1 micrograms/mg. The increase in its quantity found after infusion of heat-inactivated interleukin-1 was not statistically significant. The concentration of all three core protein fragments became reduced to a similar extent as the intact core protein under the influence of the cytokine, and additional fragments were not found. Surprisingly, there was a much smaller response to interleukin-1-treatment in patellar cartilage. PMID- 1740746 TI - Fixation stability of femoral components in a canine hip replacement model. AB - A canine hip replacement model was used to compare fixation stability in cemented and cementless femoral components. Parameters of comparison were the load-induced positional changes of each prosthesis relative to its proximal femoral cortex, hereafter called relative displacements. Identical femoral components, with the proximal third of their stem porous-coated, were implanted in the right femurs of 10 large, mixed-breed dogs. Five were tightly fit to allow porous ingrowth, and five were cemented into the medullary canal. Four months after implantation, all femurs were harvested. A prosthesis was implanted in the left (normal) femur of each dog ex vivo with fixation identical to the contralateral limb to simulate acute postoperative fixation. Eddy current transducers measured relative displacements under application of static loads, serially applied in the axial, mediolateral, and craniocaudal directions. Thereafter, the femurs were transversely sectioned and morphologically analyzed to correlate bony apposition at the implant surface with relative displacements. We observed no difference in relative displacements between acute and 4-month-cemented groups (e.g., 0.0059 +/ 0.0021 vs. 0.0060 +/- 0.0048 mm, respectively, for 100-N axial loading measured at midstem). With cementless implantation, relative displacements of the acute group were significantly larger (p = 0.007) than those of the 4-month group (e.g., 0.236 +/- 0.257 vs. 0.097 +/- 0.129 mm, respectively, for 100-N axial loading measured at midstem). Cementless components implanted for 4 months were not significantly different than cemented components, but a trend suggested that they were still not as stable as cemented components, particularly for craniocaudal loads. Relative displacements of the 4-month, porous ingrowth group were approximately proportional to the percentage of bony apposition raised to the -1.44 power (r = 0.94). PMID- 1740747 TI - Comparative study of factors relating to HIV risk level of black homeless women. AB - A comparative study was conducted to assess factors that relate to level of HIV risk of black homeless women. The study examined whether 460 black women categorized as high, moderate, or low risk for HIV infection differed in environmental, demographic, and personal factors; appraisal of threat; resources; coping responses; and health outcome. Multivariate analyses of variance revealed high-risk homeless women reported statistically significant and greater concerns, appraisal of threat, emotion-focused coping, depression, and emotional distress, as well as less self-esteem and sense of coherence than moderate- and low-risk homeless women. Discriminant analyses revealed that women at high risk for HIV infection were best differentiated from moderate- and low-risk women by greater use of emotion-focused coping, greater severity of concerns, greater depression, and less self-esteem. An understanding of psychosocial factors most predictive of groups at highest risk for HIV infection provides impetus for interventional programs focused on altering the course of the disease in this population. PMID- 1740748 TI - Central nervous system manifestations in human immunodeficiency virus infection without AIDS. AB - To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominantly mild hearing impairment. Mean performance scores for a 15 test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of less than 5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon. PMID- 1740749 TI - Pharmacokinetics of single and chronic dose zidovudine in two HIV positive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). AB - The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay. ZDV serum half-lives on day 1 were 7.9 h (patient 1) and 2.6 h (patient 2). The apparent GZDV half-lives on day 1 were 19.9 h (patient 1) and 7.1 h (patient 2), with resultant accumulation of metabolite (up to 36 micrograms/ml) during chronic therapy. At 14 h following single dose, 8.2 +/- 0.4% of dose was recovered in dialysate as GZDV; ZDV accounted for less than 0.6% of dose recovered in dialysate after both single and multiple dose. After the initial dwell (tau) following single dose, peritoneal clearances of ZDV were 4.3 ml/min (tau = 4 h, patient 1) and 5.9 ml/min (tau = 5 h, patient 2), and GZDV clearances were 6.7 and 5.1 ml/min, respectively. ZDV serum protein binding was less than 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD. PMID- 1740750 TI - Identification of HIV-1 envelope glycoprotein in the serum of AIDS and ARC patients. AB - Binding of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein (gp120) has been reported to alter the function and surface antigen expression of lymphocytes and monocytes in vitro. To determine whether these in vitro findings could be relevant in vivo, we searched for the presence of this antigen in the serum of patients with AIDS and the AIDS-related complex (ARC). Using an antigen capture enzyme-linked immunosorbent assay (ELISA) with polyclonal anti-gp120 antibody, we detected envelope antigens (gp160/120) in serum of 22 of 32 AIDS patients. In contrast, an ELISA using solid-phase recombinant CD4 to capture gp160/120 failed to detect any positives. A modification of the anti-gp120-based ELISA identified gp160/120-IgG immune complexes in all of 11 AIDS patients tested and in 4 ARC patients who were negative for gp160/120 antigen. We conclude that gp160/120, predominantly in the form of immune complexes, can be identified as circulating antigen in patients with AIDS. The potential pathogenic consequences of this antigenemia, its relation to soluble CD4 therapy, and its application as a clinical marker of disease merit further study. PMID- 1740751 TI - The completeness of AIDS surveillance. AB - AIDS surveillance data are widely used in setting HIV intervention policies, and the effectiveness of these data depend on their completeness. We reviewed studies conducted by state and local health departments on the completeness of AIDS reporting. These studies identified AIDS cases through alternate data sources, such as death certificates, hospital discharge records, disease registries, or medication records. In most instances greater than 80% of AIDS cases detected through these studies had been reported, although lower levels of reporting were found in some outpatient settings. A comparison of vital records and AIDS surveillance confirmed that AIDS surveillance is identifying 70-90% of all HIV related deaths in men 25-44 years of age. Historically, AIDS surveillance has emphasized reporting from hospitals. Efforts to maintain current levels of reporting, or to improve reporting, are challenged by the growth of the epidemic and by the increasing role of outpatient diagnosis of AIDS. PMID- 1740752 TI - A model for the AIDS epidemic in Mexico: short-term projections. AB - As in many developing countries, the AIDS epidemic in Mexico has become a major public health problem. Given the competition for scarce health resources in Mexico, where hospitals are overcrowded and care for AIDS patients is often unavailable, planning depends on accurate estimates of the incidence of AIDS and the prevalence of HIV-1 infection. This article presents estimates of AIDS incidence in Mexico corrected for delays in reporting and short-term projections based on the corrected AIDS incidence. Trends in incidence cannot be assessed without such correction because only about 50% of AIDS cases are reported within 4 months of diagnosis. In addition to information on AIDS incidence, short-term projections also require estimates of the latency distribution between infection with HIV-1 and onset of AIDS. Latency periods with medians of 8 and 10 years lead to estimates that 22,000 and 24,000 new AIDS cases infected before June 1989 will be diagnosed between 1989 and 1994. PMID- 1740753 TI - Polymerase chain reaction in detecting HIV infection among seropositive infants: relation to clinical status and age and to results of other assays. AB - The polymerase chain reaction (PCR) for human immunodeficiency virus (HIV) was evaluated using coded blood specimens from infants whose clinical status is now known. A micromethod for the efficient isolation of mononuclear cells from small volumes of blood, and definitions of PCR positivity that took into account the number and purity of these mononuclear cells, were established in an attempt to define parameters for quality assurance. Results of HIV culture, p-24 antigen, and HIV-specific IgA obtained on the same specimens were compared to PCR results. PCR had a specificity of 100% among 83 specimens from 50 babies known to be uninfected. Sensitivity among 26 HIV-infected infants older than 3 months was 98% (44 of 45 specimens); the one negative specimen, which had also been culture negative, gave a positive PCR result on the remaining aliquot when tested after decoding. Among infected infants less than 3 months old, which is an age when diagnosis by other assays is most problematic, PCR identified 10 of 10 patients (10 of 11 specimens) including two younger than one month. Viral culture showed the best concordance with PCR; however, in three infants, positive PCR results were observed several months before positive results were observed by viral culture. PMID- 1740754 TI - Characteristics associated with HIV-1 infection in pregnant women in Brazzaville, Congo. AB - Maternal human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan Africa is a major public health concern because of the high prevalence among women of childbearing age and the poor prognosis for perinatally infected children. Characteristics associated with HIV seroprevalence were studied in a population of 1,833 pregnant women seen in two large mother-child clinics in Brazzaville, Congo. The prevalence of HIV infection was 3.9% (95% confidence interval, 3.0-4.9%) and differed significantly according to the district of residence, marital status, duration of the relationship with the current partner, number of sexual partners in the year prior to pregnancy, number of living and dead children, and history of blood transfusion and/or hospitalization. Logistic regression analysis identified six significant factors independently associated with seropositivity; age, history of blood transfusion and/or hospitalization, district of residence, duration of the relationship, number of living children, and number of decreased children. However, the predictive value of the model was poor: while 80% of the truly positive women were correctly predicted positive by the model, 50% of the truly negative women were misclassified. Among pregnant women attending these clinics it is therefore difficult to identify a subgroup at risk toward which specific actions could be targeted. PMID- 1740755 TI - Improved detection of HIV-2 DNA in clinical samples using a nested primer-based polymerase chain reaction. AB - A two-step polymerase chain reaction (PCR), with four double (nested) primer pairs, used for the detection of HIV-2 in clinical samples is described. With these four nested primer pairs we could detect HIV-2 DNA in 17 of 17 virus isolates and in blood mononuclear cell samples from 31 of 37 (83.7%) seropositive individuals after ethidium bromide staining of the amplified DNA. The nested primer PCR was also compared with a single primer pair-based PCR followed by hybridization. The sensitivities of the two methods were almost equal, but the nested primer PCR offered obvious technical advantages. PMID- 1740756 TI - Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies. AB - The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48 164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection. PMID- 1740757 TI - An amino-terminal amino acid affects the electrophoretic mobility of the HIV-1 nef protein. AB - The nef protein of the BH8 clone derived from the IIIB isolate of human immunodeficiency virus 1 (HIV-1) has a molecular weight of 27,000, whereas that produced by a clone of the BRU strain of HIV-1 appears to have a molecular weight of 24,800. To determine the basis for this difference in molecular weight, a series of recombinant nef genes were made in which segments of the BH8 and BRU nef coding sequences were exchanged. The region of amino acids 35-74 caused mobility shift. In this region, the BH8 and BRU proteins differ by a single amino acid at position 54. Residue 54 of BH8 nef is an aspartic acid, whereas that of BRU is alanine. Reciprocal changes in the sequences of BH8 and BRU nef were made by site-directed mutagenesis. The results show that substitution of aspartic acid at residue 54 of BH8 to alanine results in a protein that has a molecular weight of 25,000, and substitution of the alanine at position 54 of BRU to aspartic acid results in synthesis of a 27-kDa protein. These results show that a change in amino acid 54 of the HIV-1 nef protein dramatically affects the electrophoretic mobility of the protein. Nef proteins that contain an aspartic acid at residue 54 migrate as 27-kDa proteins, whereas those that contain alanine at residue 54 migrate as 25-kDa proteins. PMID- 1740758 TI - Instability of HIV sequences in high copy number plasmids. AB - Plasmid proviral molecular clones of the LAI isolate of HIV-1 and the ROD isolate of HIV-2 were originally prepared in moderate copy number plasmids derived from pBR322, which contains the colE1 origin of replication. In these plasmid vectors, the HIV sequences are stable to continuous passage in bacteria. However, when the colE1 origin was replaced by the mutant origin from pUC18, pGEM, or pBluescript plasmids, which replicates to much higher copy numbers in bacteria, then deletions of HIV sequences occurred even in RecA defective strains. Deletions occurred in two different media, at room temperature and 37 degrees C, and with or without plasmid amplification in the presence of chloramphenicol. These results raise a cautionary note when cloning immunodeficiency viral sequences into plasmid vectors containing a high copy number origin of replication. PMID- 1740759 TI - Prevalence of HIV infection among prostitutes in Benin (West Africa) PMID- 1740760 TI - HIV-2 infection in Cameroon: no evidence of indigenous cases. PMID- 1740761 TI - Natural disease--unnatural cause. PMID- 1740762 TI - A health hazard assessment in school arts and crafts. AB - Unlike the cautious attitude being exercised toward generic chemicals, an off guard behavior is often observed toward the same chemicals once they are recognized as a "common daily item." Students and instructors of arts and crafts classes alike are often unaware of the potential risks from exposure to some of the arts and crafts materials they use due to either the false security of "common daily item" or the lack of specific knowledge of the hazardous ingredients in those products. This unawareness of potential health hazards could lead to improper handling of these materials and result in unnecessary health risk during their use. A three-year study of college arts and crafts class students indicates a high incidence of allergic reactions among attending students for exposure of less than 70 hours within a period of 7 weeks. A self evaluation method is developed to identify and minimize these health hazards associated with arts and crafts classes. This checklist of 15 pertinent parameters covers identifiable hazardous areas and situations in arts and crafts classrooms. Record keeping and promotion of student awareness are also addressed, so that instructors and students in an arts and crafts class can more readily recognize actual or potential hazards and act to prevent them. PMID- 1740763 TI - Health hazards associated with the cyanotype printing process. PMID- 1740764 TI - Industrial hygiene survey in a university art department. AB - Analysis of air samples indicated that concentrations of respirable free silica from sandblasting equipment used inside an unventilated painting room greatly exceeded the current OSHA standard and NIOSH recommended criteria. Lack of ventilation in the design materials studio resulted in excessive wood dust concentrations; levels averaged 29 mg/m3 which was well above the evaluation criteria of 5 mg/m3. Noise levels measured in the woodworking area of the design materials studio, and near the melting furnace located in the foundry of the ceramics studio, exceeded the 100-dBA limit recommended by NIOSH for a 2 hr continuous exposure. Lack of proper ventilation in the design materials painting room and in the printmaking darkroom resulted in exposures to toxic concentrations of toluene (from spray painting) and methyl cellosolve acetate (from KPR photo etching chemicals). Results of atmospheric sampling indicate that exposure to wood dust, crystalline silica, methyl cellosolve acetate, and toluene were excessive, and capable of producing both acute and long term health effects. PMID- 1740765 TI - The first art hazards course. PMID- 1740766 TI - A waste disposal program for a university art department. AB - With the introduction of hazardous waste regulations on May 19, 1980, many of the wastes generated and disposed of by university art departments are now considered hazardous wastes by law. Pollution Control, an operational department within Southern Illinois University, Carbondale, charged with the environmental compliance of the University, has developed a hazardous waste management program for the safe and proper disposal of these wastes. Wastes that can pose a threat not only to the artist, but also to the disposer of the wastes and the environment, are included in this program to prevent haphazard or indiscriminate disposal. Major functions of the program include identification of such wastes, collection, storage, treatment, and, finally, environmentally safe disposal of the waste. PMID- 1740767 TI - Hepatocellular injury induced by chronic low-dose CCl4 in spontaneous and renal hypertensive rats: a correlation to the reversal of experimental rat hypertensive models. AB - Renal hypertension has been reduced to normal levels in the rat with subcutaneous injections of carbon tetrachloride (CCl4). Previous light microscopic evaluation of liver sections demonstrated varying degrees of hepatocellular and hepatic parenchymal injury secondary to CCl4 administration. In normotensive rat populations, saline injections have been shown not to cause hypertension, and the treatment of normal rats with subcutaneous CCl4 did not change their blood pressure over that of noninjected controls. In this study we compare the extent of blood pressure reduction with the degree of CCl4-induced liver injury in the renal-induced, spontaneous hypertensive rat (SHR), and normotensive rat. Statistically significant blood pressure reduction followed CCl4 injection of renal (p less than .01) and SHR (p less than .001) hypertensive animals. The morphological liver injury appeared most sensitively reflected in hepatocellular nuclear atypia. The SHR animals were the most resistant to CCl4 liver damage by chronic CCl4 treatment. There was no measurable effect of CCl4 treatment on the animals as assessed by their activity, rate of development and weight gain. The degree of blood pressure reduction due to CCl4 treatment in the SHR animals was similar to that previously reported in DOCA and renal-induced hypertensive animals. PMID- 1740768 TI - Protective and therapeutic efficacies of protein A on 7,12 dimethylbenz(alpha)anthracene-induced rat mammary adenocarcinoma. AB - Protein A of Staphylococcus aureus Cowan I is a powerful immunostimulating agent. Female Swiss Portan rats fed 7,12-dimethylbenz(alpha)anthrancene (DMBA) exhibited increased serum alkaline phosphatase activity, which returned to normal levels following eight weeks of treatment with 12 micrograms protein A subcutaneously. Protein A reduced the potential of tumor induction by DMBA as observed by the noninduction of tumors until three months after discontinuation of protein A administration. The total leukocyte count was not affected. Protein A treatment for six weeks of DMBA-induced mammary adenocarcinoma-bearing rats caused the increased serum alkaline phosphatase activity to decrease but not to normal levels, indicating regression but no disappearance of the tumors. The total leukocyte count of the tumor bearers was stimulated by protein A and increased 24 hours after protein A administration; however, in the fourth week of treatment it returned to normal levels. The leukocytosis suggests that protein A could cause tumor necrosis by an inflammatory reaction, edema, and cell destruction and thus tumor regression. PMID- 1740769 TI - The biosynthesis of polyketide-derived mycotoxins. AB - The biosynthesis of a few representative polyketide-derived mycotoxins is reviewed: patulin, citrinin, diplosporin, ochratoxin A, maltoryzine, xanthomegnin, cytochalasans, ergochromes, zearalenone, citreoviridin, and the aflatoxins. Particular attention is given to the biosynthetic sequence: acetate-- -averufin----versiconal acetate----versicolorin A----sterigmatocystin--- aflatoxin B1. PMID- 1740770 TI - Detoxification of aflatoxin-polluted peanut cakes with monomethylamine/Ca(OH)2: pilot industrial application, nutrition experiments, toxicity evaluation. AB - The process described has been studied up to an industrial pilot scale. In this article this article we summarize the basic knowledge on the process and the technological conditions of pilot application for detoxifying peanut cakes polluted by up to 3,500 ppb Aflatoxine (2,300 ppb B1). The nutritional experiments carried out on rats and other mammals are described, and the toxicological and biochemical evaluation of the cakes on Bacillacea are reported and discussed. The data collected show that the MMA/Ca(OH)2 process offers promising possibilities for industrial application on the basis of technological and economic criteria, as well as from the point of view of efficiency and safety. PMID- 1740772 TI - Desert Storm 1991: orthopaedic related surgical injuries. PMID- 1740771 TI - Lead poisoning from art restoration and pottery work: unusual exposure source and household risk. AB - Two cases of lead poisoning following exposures in the arts and crafts environment are presented. The first illustrates the impact of an unusual exposure source experienced by a female art conservator while restoring an antique Peruvian tapestry from the Chancay Period (A.D. 1000-1500). The second demonstrates the extension to the artist's family members of a lead hazard associated with pottery work. Noted were a wide spectrum of clinical and biochemical abnormalities, ranging from severe neurological and gastrointestinal symptoms to subtle alterations in the biosynthetic pathway of heme. Marked elevation of the blood lead level (up to 130 mcg/100 mL) was found in the most severe case of lead poisoning. The cases illustrate the need for industrial hygiene measures in this type of work in order to prevent lead intoxication, both in the adult artist and children in the household. However, in some instances of increased lead absorption in persons with lead-related hobbies, sources other than those associated with arts and crafts should be investigated. This alternative is illustrated by a third case, in which firearms training was the more likely source of excessive exposure. Multiple occupational factors must occasionally be considered in evaluating increased lead absorption. PMID- 1740773 TI - Re: Below-knee amputee gait with dynamic elastic response prosthetic feet: a pilot study. PMID- 1740774 TI - Design and evaluation of a sensory feedback system that provides grasping pressure in a myoelectric hand. AB - Providing accurate sensory information to the individual with a myoelectric limb is of great importance for improving device use in a wide variety of tasks. A number of feedback systems presently being investigated rely on either vibrotactile or electrotactile skin stimulation, which does not provide sensory patterns similar to those in a natural grasping hand. A prototype system was developed to enhance sensory information transfer by using a technique in which the feedback modality (pressure) was the same as the grasping pressure. The present study compared the developed system (pressure) with vibrotactile feedback, vision, and compounds of these three modes. It was found that the pressure-pressure concept reduced grasping pressure replication errors and error variability. PMID- 1740775 TI - A portable insole plantar pressure measurement system. AB - To analyze plantar pressures during activities of daily living, one needs a fully portable system capable of measuring many steps over extended periods. This paper presents an inexpensive, reliable, portable plantar pressure acquisition system which we have developed. It allows the long-term recording (up to 2 hours) of pressure-time data from 14 pressure sensors within insoles. The sensor chosen is an inexpensive, conductive polymer sensor that is only 0.25 mm thick yet able to withstand sudden overloads. The portable, battery-powered, microprocessor-based data acquisition system has a memory space of 480 kbytes for data storage. It can collect pressure data from 14 insole sensors at a 20 Hz sample frequency for 5 seconds every minute over a 2-hour period. It enables the long-term measurement of plantar pressures during normal activities in a natural unrestricted environment. The design and development of this portable insole plantar pressure measurement system is described. PMID- 1740776 TI - Development of an automated wheelchair guided by a magnetic ferrite marker lane. AB - An automated wheelchair with a guide sensor, guided by a magnetic ferrite marker that is resistant to the presence of dirt, is described. The wheelchair permits the severely disabled, as well as the older population, to move about freely, both indoors and outdoors. This is due to the simple operation involved (pushing a button), and a magnetic ferrite marker lane which is minimally influenced by dirt or other nonmagnetic materials. For increased comfort, a nonlinear signal processing circuit and pulse-steering drive method have been developed to provide a smooth running operation. In addition, a function that provides for stopping at desired destinations has been added for convenience, and a collision prevention function using infrared sensors has been added for safety. PMID- 1740777 TI - Safety studies with the University of Melbourne multichannel electrotactile speech processor. AB - Results of safety investigations conducted as an integral part of the development of a multichannel electrotactile speech processor (Tickle Talker) are reported. Electrical parameters of the stimulus waveform, design of the electrode handset and cabling, and the electrical circuitry of the speech processor/stimulator and programming interface have been analyzed for potential risks. Constant current biphasic square pulses delivered to electrodes positioned on the skin surface over the digital nerve bundles were chosen to optimize the safety, comfort, and function of the electrotactile stimulus. The device was battery-powered, and the user circuit was isolated from earth-referenced sources. Each electrode was isolated by capacitive coupling, preventing DC leakage of current to the user circuit. Studies of finger temperature showed slight cooling of the skin on the fingers of both stimulated and unstimulated hands for individual subjects following electrotactile stimulation through the Tickle Talker. Subsequent analysis of finger and hand vascular circulation in five subjects showed slight reductions in hand blood flow in some individuals. The results did not demonstrate a significant mean decrease in hand or finger blood flow following electrotactile stimulation. No evidence of sympathetic involvement was found, nor were any changes in vascular structure of the hand such as those associated with Raynaud's disease found. Evidence suggests that the decrease in temperature found in the initial study may be due to a change in the ratio of blood flow between arteriovenous anastomoses and nutritive capillary beds. Studies of: 1) changes in mean threshold and comfortable pulse widths over time; and, 2) changes in tactual sensitivity as measured by hot/cold, sharp/dull, and two-point difference limen discrimination, did not detect any systematic change in peripheral nervous system function following electrotactile stimulation. Analysis of electroencephalogram (EEG) recordings taken during electrotactile stimulation, and after relatively long periods of experience with the device did not show any pathological changes which might be associated with epileptic foci. In summary, no contraindications to long-term use of the Tickle Talker were detected in the studies performed. PMID- 1740778 TI - Speech recognition performance on a modified nonsense syllable test. AB - A modification of the City University of New York nonsense syllable test (CUNY NST) has been developed in which (a) the several subtests of the original test are replaced with a 22-item consonant-vowel (CV) subtest and a 16-item vowel consonant (VC) subtest; and, (b) the response choices for each target syllable include all 22 initial and all 16 final consonants, respectively. In addition, the test tokens are presented as isolated syllables without a carrier phrase. These changes enable the resolution of confusions not possible on the original NST, and also the construction of a single confusion matrix each for CVs and VCs, respectively. The modified nonsense syllable test (MNST) provides results that compare favorably to those of the original NST. PMID- 1740779 TI - Effect of functional bracing, quadriceps and hamstrings on anterior tibial translation in anterior cruciate ligament insufficiency: a preliminary study. AB - Anterior tibial translation was measured in six patients with anterior cruciate ligament insufficiency. The tests were done in 15, 45, and 90 degrees of knee flexion, partly with activated quadriceps or hamstrings, and partly with subjects wearing a 4-point functional DonJoy brace. The translation was evaluated with a computerized electrogoniometer (Acufex KSS). The anterior tibial translation was significantly reduced by use of the hamstrings in all three degrees of knee flexion. The effect of the 4-point brace was only significant in 15 and 45 degrees of flexion. The quadriceps did not reduce the anterior tibial translation. PMID- 1740780 TI - Epithelial respiratory cells from cystic fibrosis patients do not possess specific Pseudomonas aeruginosa-adhesive properties. AB - Nasal polyp cells in primary culture from cystic fibrosis (CF) and non-CF patients were compared for the ability to bind Pseudomonas aeruginosa cells and for the presence of sulphated glycoconjugates at the epithelial cell surface. Quantitation of bacterial adhesion, by scanning electronmicroscopy, showed no significant difference between the cells cultured from CF and non-CF patients. Micro-organisms associated with ciliated cells were mainly aggregated, in contrast with those from non-ciliated cells. Sulphated glycoconjugates were identified on cells cultured from both CF and non-CF patients, regardless of whether or not these cells had attached bacteria. A matrix-like material that surrounded the aggregated bacteria was more prominent on cells cultured from CF patients than on those from non-CF patients. The interaction of aggregated P aeruginosa cells with polyp cells cultured from both CF and non-CF patients appeared to occur by means of this matrix material. Our findings suggest that chronic colonisation of the airways of CF patients cannot be explained by an increased affinity between the P. aeruginosa cells and the respiratory cell surface receptors in the CF patient. Nevertheless, the in-vitro observation that the matrix surrounding the bacteria reacted with a monoclonal antibody against respiratory mucins allows us to speculate that increased mucin secretion by cells from CF patients might, in vivo, play a decisive role in the interaction between P. aeruginosa and the respiratory epithelium. PMID- 1740781 TI - The protective activity of immunostimulants against Listeria monocytogenes infection in mice. AB - The function of peritoneal macrophages induced by intraperitoneal (i.p.) injection of attenuated Streptococcus pyogenes (OK-432), Bacillus Calmette Guerin (BCG), protein-bound polysaccharide preparation isolated from Coriolus vesicolor (PSK) or Lactobacillus casei was examined. The PMA-triggered respiratory burst (production of O2- and H2O2) of macrophages induced by OK-432, BCG or Lac. casei was greater than that of resident or thioglycollate-stimulated macrophages and was similar to that of BCG-activated macrophages. PSK failed to enhance the production of O2- or H2O2 by macrophages. Alkaline phosphodiesterase (APD) activity was reduced in macrophages induced by OK-432, BCG or Lac. casei injection and in BCG-activated macrophages. The APD activity of macrophages obtained 7 and 13 days after i.p. injection of PSK was elevated, as with thioglycollate-stimulated macrophages. Listericidal activity in vitro was enhanced in macrophages obtained in 13 and 7 days, but suppressed in macrophages obtained 2 days after OK-432, BCG or Lac. casei injection. Lac. casei administered either 2 or 13 days before infection with Listeria monocytogenes was protective but OK-432, BCG (0.1 mg) and PSK were not, even though they were able to stimulate macrophage function. PMID- 1740782 TI - Congenital bacterial sepsis in very preterm infants. AB - The results of body fluid and surface cultures from 148 preterm infants less than 33 weeks gestational age obtained routinely on admission to a neonatal intensive care unit were reviewed. The aim was to determine the occurrence of congenital bacterial sepsis in this population and to examine whether surface cultures yielded information helpful in management. Gastric aspirate and umbilical, nasal and ear swabs were cultured and the results were compared to those of blood cultures. Nine infants (5.4%) had congenital bacterial sepsis diagnosed by positive blood cultures. Only the results of microscopy of gastric aspirate were available within hours of birth and before the results of blood culture. Microscopy of gastric aspirate, demonstrating pus cells, alone had a sensitivity of 0.86 in predicting congenital sepsis but a specificity of 0.49; the specificity, however, rose to 0.80 if both organisms and pus cells were observed on microscopy. Thus, only this combination was a useful pre-indicator of congenital sepsis. In infants who did not develop septicaemia, treatment was modified only if Streptococcus agalactiae was cultured from surface sites; in all such cases, the organism was grown from the ear swab. Our results demonstrate that congenital bacterial sepsis is common amongst very preterm infants admitted for neonatal intensive care but routine screening of surface cultures should be restricted to an ear swab only. PMID- 1740783 TI - Diagnostic significance of circulating immune complexes in patients with pulmonary tuberculosis. AB - A polyethylene glycol (PEG) precipitation method was used to examine sera of patients with active pulmonary tuberculosis (PT), leprosy and non-tuberculous pulmonary diseases and of healthy control subjects for immune complexes (ICs). Mycobacterium tuberculosis antigen 5 was detected in the ICs in 80% of patients with PT by the indirect (sandwich) enzyme-linked immunosorbent assay (ELISA). Detection of mycobacterial antigen in ICs has diagnostic potential as an adjunct in the laboratory diagnosis of PT, particularly when repeated bacteriological investigations for M. tuberculosis in clinical specimens are negative. Levels of ICs tend to decrease with the duration of anti-tuberculosis chemotherapy and their detection can also be used to assess the clinical response to therapy in patients with PT. PMID- 1740784 TI - Factors affecting production of the group A streptococcus bacteriocin SA-FF22. AB - Factors influencing the production of streptococcin A-FF22 (SA-FF22) in liquid media were examined. Despite good growth of the producer strain, no SA-FF22 was detected during incubation at 40 degrees C, at pH 7, in Brain Heart Infusion Broth or in Mg(2+)-supplemented media. Optimal SA-FF22 production occurred at 32 degrees C, at pH 6.7, in cultures in Tryptic Soy Broth supplemented with glucose 2.25% and yeast extract 1%. Under these conditions SA-FF22 remained cell associated but could be extracted with acid. PMID- 1740785 TI - Use of antibiotics in veterinary practice. PMID- 1740786 TI - An experimental evaluation of the pharmacokinetics of fusidic acid in peritoneal dialysis. AB - Fusidic acid, an antimicrobial agent with activity against coagulase-positive and coagulase-negative staphylococci, has considerable potential for the management of staphylococcal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Whether fusidic acid reaches therapeutic levels in the dialysate once therapeutic serum levels have been achieved is not known. An animal model of CAPD that reproduced essential features of the clinical procedure was used to investigate this issue. Although oral administration was the preferred route, fusidic acid is not absorbed from the gastrointestinal tract of laboratory rats, and a subcutaneous injection of diethanolamine fusidate was used to achieve serum levels of the agent equivalent to those achieved clinically in man. In this model, fusidic acid concentrations up to 28 times the MIC for staphylococci were found in the dialysate when therapeutic levels of the agent were reached in the serum. The data provide support for continued experimental and clinical evaluation of the role of fusidic acid in CAPD-associated peritonitis. PMID- 1740787 TI - Induction of the SOS gene (umuC) by 4-quinolone antibacterial drugs. AB - Induction by the 4-quinolone group of antibacterial drugs of the umuC gene, the SOS function most involved in error-prone DNA repair (together with umuD), was assessed in a strain of Escherichia coli harbouring a umuC::lacZ gene fusion. All 4-quinolones tested induced this umuC::lacZ fusion, with maximum induction at 4 quinolone concentrations close to their minimum inhibitory concentrations for this strain, and the SOS Inducing Potential (SOSIP) was closely related to antibacterial activity. Mitomycin C, a known mutagen, was a slightly better inducer (in terms of SOSIP) than any of the quinolones. In contrast, induction by 4-quinolones of the sfiA (sulA) gene, an SOS function involved in cell division inhibition, was better than induction by mitomycin C in an E. coli strain harbouring an sfiA::lacZ gene fusion. The umuC gene fusion was induced at lower concentrations of 4-quinolone than was the sfiA gene fusion. PMID- 1740788 TI - Incidence of an aminoglycoside 6'-N-acetyltransferase, ACC(6')-1b, in amikacin resistant clinical isolates of gram-negative bacilli, as determined by DNA-DNA hybridisation and immunoblotting. AB - Seventy amikacin-resistant clinical isolates of gram-negative bacteria belonging to nine genera were examined by immunoblotting and by DNA-DNA hybridisation for the presence of ACC(6')1b enzyme, previously called AAC(6')-4, or its encoding gene aacA1b. The organisms mostly had resistance profiles compatible with AAC(6') production and were from South and North America, the Far East and Europe. Polyclonal (rabbit) anti-AAC(6')-1b antisera and an intragenic aacA1b (aacA4) probe derived from the multiresistance plasmid pAZ007 were used. The aacA1b gene was found to be widespread. Positive hybridisation, and immunologically cross reactive proteins, were observed in 44% of the isolates examined. They were present most frequently (greater than or equal to 70%) in isolates of Klebsiella, Escherichia and Enterobacter spp., but less often (less than or equal to 25%) in Serratia, Citrobacter, Acinetobacter and Pseudomonas spp. The strains that reacted with the probe produced enzymes that varied in their apparent mol. wts between c. 24,000 and 26,000. The existence of multiple electrophoretic forms of amikacin-acetylating enzymes of the ACC(6')-1b type may be useful in epidemiological surveys of AAC(6')-mediated amikacin resistance. PMID- 1740789 TI - An investigation of beta-lactamases from clinical isolates of Bacteroides species. AB - Among a group of 116 clinically significant isolates of Bacteroides spp., 24 exhibited beta-lactamase activity greater than the basal level characteristic of most Bacteroides strains. Investigation of specific enzyme activity, iso-electric point and enzyme inhibition profiles revealed that the beta-lactamases involved could be divided into four groups, some showing similarity to those described in previous studies. Seven of the enzymes were able to hydrolyse cefoxitin, latamoxef or imipenem, and eight enzymes degraded penicillin in the presence of clavulanic acid. Five strains showed reduced susceptibility to cefoxitin, latamoxef or imipenem which was not associated with beta-lactamase activity. PMID- 1740790 TI - The rectal mucosa-associated microflora in patients with ulcerative colitis. AB - The rectal mucosa-associated flora (MAF) of patients with ulcerative colitis has been studied in 25 patients with newly diagnosed disease, 20 with relapse of existing disease, and 44 who were in remission. Patients with active disease were re-examined twice during treatment. The MAF was simpler and less dense than the microflora of faeces. Obligate anaerobes usually predominated in the MAF although the ratio of obligate anaerobes to facultative species was lower than that found in faeces. Viable counts of the total flora and of its constituent genera varied considerably between patients. Counts of the total flora, of obligate anaerobes (including bifidobacteria, eubacteria and clostridia), and facultative organisms and micro-aerobes (enterobacteria and lactobacilli) were reduced in patients with active disease compared with those with inactive disease; corresponding carriage rates were also lower. Counts and carriage rates increased during treatment and approached those found in quiescent disease. The alterations in the MAF were especially marked in patients experiencing their first attack of ulcerative colitis. The relationship between these alterations and the aetiology and pathogenesis of this disease remains unclear. PMID- 1740791 TI - Percutaneous tracheostomy after trauma and critical illness. AB - A method of percutaneous tracheostomy (PT) using a tracheostome, which permits insertion of a full-sized cuffed tracheostomy tube, was evaluated in 61 critically ill or injured patients (89% had trauma). Of the 54 trauma patients, 65% had brain injuries, 14% had injuries to the cervical spinal cord, 33% had face or jaw injuries, and 15% had lung injuries. The indications for PT were coma (46%), acute airway obstruction (5%), face or jaw injury (20%), pneumonitis (39%), adult respiratory distress syndrome (12%), and sepsis (21%). Tracheostomy was done in 51% of all cases specifically for managing pulmonary secretions, in 37% for prolonged intubation, and in 25% for neurologic lesions. The tracheostomy was done as an emergency in 5%, as urgent in 28%, and electively in 77%. Percutaneous tracheostomy was successful in 90% of the cases, and in 8% it was converted to a surgical tracheostomy after an initial percutaneous attempt. In 46% it was performed at the bedside, in 46% in the operating room, and in 7% in the emergency suite. A full-sized tracheostomy tube (#6 to #8) was used in all cases and was considered optimal or larger than needed in 87% of cases. With three exceptions the complications of PT were minor, but 30% of the patients died of their primary disease. In one case death occurred because of bronchospasm and cardiac arrest during the PT, but appeared to be independent of the type of tracheostomy. Healing after in-hospital removal (37%) was excellent in 95% of cases and 97% of physicians indicated that they would use the device again. PMID- 1740792 TI - A study of the relationship among survival, gut-origin sepsis, and bacterial translocation in a model of systemic inflammation. AB - Several factors, including uncontrolled inflammation, gut barrier failure, and sepsis, have been implicated in the development of multiple organ failure. To investigate the relative importance and interrelationships among some of these factors, increasing doses of the inflammatory agent zymosan were used to induce a systemic inflammatory state in mice. At nonlethal doses (0.1 and 0.5 mg/g body weight), zymosan caused injury to the intestinal mucosa, increased intestinal xanthine oxidase activity, and promoted bacterial translocation in a dose dependent fashion. Inhibition or inactivation of xanthine oxidase activity was effective in reducing mucosal injury and bacterial translocation when zymosan was injected at 0.1 mg/g but not at 0.5 mg/g body weight. At a dose of 1 mg/g, the lethal effects of zymosan appeared to be related to gut-origin sepsis, since cefoxitin (1 mg/g) reduced the seven-day mortality rate from 100% to 20% (p less than 0.01). However, at a zymosan dose of 2 mg/g, antibiotics did not improve survival. Zymosan thus induced gut barrier failure and systemic infection in a dose-dependent fashion. Additionally, the mechanism of zymosan-induced bacterial translocation and the relationship of gut-origin sepsis to survival appeared to be related to the magnitude of the inflammatory insult (the dose of zymosan). PMID- 1740793 TI - Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion. AB - Forty dogs were divided randomly into four groups. The portal circulation was reduced to 50%-60% for one hour by partially occluding the superior mesenteric artery (SMA) for the purpose of determining the relationship between the reperfusion injury, bacterial translocation, and multiple system organ failure. Escherichia coli 0111 B4 (1 x 10(10)/kg) was fed to each animal 12 hours before operation. Group I constituted the controls, in which a sham operation was done. The experimental procedure was completed in all the animals of the other three groups. The group-II animals received no further manipulation. Rubia yunnanensis, an antioxidant, was given to the animals in group III. Amikacin was given to the animals in group IV. The results showed that the animals in group II developed bacteremia, hypoxemia, and hypotension compared with the animals in group I. The levels of superoxide dismutase (SOD) in whole blood were markedly lowered in group-II animals, with malondialdehyde (MDA) values significantly elevated after reperfusion when compared with group I. Plasma levels of anaphylatoxin C5a and thromboxane B2 (TXB2) were significantly raised in group-II animals beginning from reperfusion when compared with the animals in group I, group III, and group IV. Pathologic changes in the intestine, liver, and lung were marked only in the group-II animals, including acute necrosis of the intestinal mucosa, granulocyte infiltration, and bacterial invasion of the liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development of MSOF by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations, where it fuels the septic process. Oxygen free radicals, anaphylatoxin, and thromboxane may be potential factors in the development of gut barrier failure and MSOF. PMID- 1740794 TI - Ibuprofen lowers body temperature and metabolic rate of humans with burn injury. AB - A group of 15 burned children and young adults with large burns (mean, 41% +/- 15% BSA) were administered ibuprofen (40 mg/kg for 3 days). Each patient served as his or her own control in this crossover study (with and without ibuprofen). Paired calorimetric and temperature studies and urinary nitrogen measurements were performed. No nitrogen-sparing effect was identified for this dose of ibuprofen. However, patients demonstrated a statistically significant reduction in average rectal temperature (0.67 degrees C decreases) (p less than 0.01) and in metabolic rate (11.4% decreases) (p less than 0.01) while taking ibuprofen. Linear regression analysis of the reduction in temperature versus the reduction in metabolic rate yielded a statistically significant correlation (p less than 0.01) with a slope of 13.6% reduction in metabolic rate per degree centigrade reduction in the 72-hour average rectal temperature. These results support the hypothesis that ibuprofen attenuates the hypermetabolic response to thermal injury by blunting the temperature elevation that is usually seen. PMID- 1740795 TI - Left ventricular performance in patients with thermal injury or multiple trauma: a clinical study with echocardiography. AB - Left ventricular (LV) contractile and diastolic performance was evaluated in patients with thermal injury or multiple trauma using precordial and transesophageal echocardiography. Thirty-nine patients were divided into four groups: group B1 (within 24 hours after thermal injury); group B2 (from 24 to 72 hours after thermal injury); group M (multiple trauma); and a control group (outpatients). Left ventricular contractile indices, including ejection fraction, mean velocity of circumferential fiber shortening, and the ratio of systolic blood pressure to LV end-systolic dimension, were not impaired in any of the experimental groups. The ratio of LV filling volume during rapid filling to stroke volume, obtained from M-mode echocardiography as an index of LV distensibility, was significantly decreased in groups B1 (44.5% +/- 8.8%) and B2 (46.8% +/- 8.5%) compared with controls (61.9% +/- 7.4%) (p less than 0.05). The ratio of the peak velocity in the atrial contraction phase to that in the rapid filling phase, obtained using pulsed Doppler echocardiography, also showed significant impairment of LV distensibility in groups B1 (1.08 +/- 0.12) and B2 (1.09 +/- 0.07) compared with controls (0.71 +/- 0.12) (p less than 0.01). Group M showed no significant impairment of these diastolic indices. A profound depression of LV diastolic function thus occurs following thermal injury but not following multiple trauma. PMID- 1740796 TI - External fixation of fractures with a new frame in managing patients with multiple trauma. AB - The use of a new modular frame with the AO tubular fixator in managing the cases of severely injured patients is reported. The simplicity in design, the versatility, and the ease of insertion make this frame very useful in managing a patient with multiple injuries in the emergency department when stable fixation of a variety of fractures is needed. Our clinical experience with 23 patients, all with an ISS of 16 or greater, is reported and four representative cases are described. PMID- 1740797 TI - Blade-plating of closed displaced supracondylar fractures of the distal femur with the AO system. AB - We reviewed a series of 42 closed and displaced supracondylar and intercondylar fractures of the distal end of the femur that were treated over a 7-year period by open reduction and internal fixation using the AO system (blade-plate). A strict rating scale incorporating subjective data and objective motion of the involved knee was used for the results. At a mean follow-up of 5 years, the results in eight patients were rated excellent, the results in 14 were rated as good, the results in 11 as fair, and the results in nine as poor. Complications were found in 15 patients (37.5%). Complications included postoperative osteomyelitis in two; nonunions in three; malunions in two; delayed unions in two; marked loss of knee motion in four; and superficial infection and wound hematoma in one patient each. PMID- 1740798 TI - Necrotizing fasciitis of the extremities. AB - Necrotizing fasciitis is a limb- and life-threatening soft-tissue infection. Eighteen patients with necrotizing fasciitis of the extremities were reviewed. These infections occurred most commonly after minor trauma. Associated chronic debilitating diseases were present in 13 patients. All but two infections were polymicrobial. The overall mortality rate was 33%. Death was caused by persistent wound sepsis in three and systemic septic complications in spite of apparent local infection control in three. At the admission physical examination the condition may resemble a benign, low-grade cellulitis. Three of four patients died because of a delay in surgical debridement for more than 24 hours after admission. Multiple radial debridements of the involved skin, fat, and fascia are essential to control progressive necrosis. Our results suggest that early diagnosis and prompt surgical debridement of necrotizing fasciitis are essential for survival. PMID- 1740799 TI - Anterior compartment syndrome of the thigh in athletes--indications for conservative treatment. AB - Anterior compartment syndrome of the thigh resulting from blunt contusion without an accompanying fracture is rare. The treatment advocated for it by most authors has been surgical. However, because wound infection rates are high and loss of knee range of motion is frequent, we considered conservative treatment in selected patients. Six athletes who developed an anterior thigh compartment syndrome shortly after sustaining a blunt contusion to the quadriceps with an accompanying massive hematoma were studied prospectively. Tissue pressure, renal function, and creatinine phosphokinase (CPK) levels were closely monitored. Fasciotomy was not performed, despite sustained pressure elevations above 50 mm Hg. Neurologic function was not affected. At follow-up examination 1 year later, no limitation of joint motion nor weakness of the quadriceps were observed. Thus in selected young patients in whom an isolated anterior compartment syndrome of the thigh occurs, conservative treatment yielded results superior to fasciotomy. PMID- 1740800 TI - Emergency department record keeping and the potential for injury surveillance. AB - Successful design of injury prevention measures relies on understanding the occurrence and circumstances of injuries, which, in turn, necessitates that good quality data be collected about injured persons. The emergency department (ED) is an important source of injury information. This paper reports the results of a survey of all 129 hospital emergency departments in North Carolina to examine record-keeping practices and determine what information is collected and stored in the EDs. The findings demonstrate that there is considerable variability in the types of data that would be available to a researcher attempting to use ED records. Of special note is the absence of information about the external cause of injury. PMID- 1740801 TI - The effect of hypothermia on liver adenosine triphosphate (ATP) recovery following combined shock and ischemia. AB - During both hemorrhagic shock and ischemia, adenosine triphosphate (ATP) concentrations fall in liver tissue. Incomplete recovery of ATP correlates with cell death and subsequent organ dysfunction. Changes in liver ATP levels were evaluated in paired groups of rats subjected to combined hemorrhagic shock and ischemia. A second set of paired animals was studied over time with shock alone. One animal in each pair was maintained at 28 degrees C and the other at 37 degrees C. Ischemia was produced by occluding inflow to the left half of the liver, and tissue was obtained from this area in all animals studied. Adenosine triphosphate levels fell in warm and cold animals subjected to both shock and 60 minutes of ischemia but recovered more completely during reperfusion in the cold animals. Shock alone caused a steady fall in ATP levels in the warm, but not the cold rats. These biochemical changes may indicate a beneficial effect of moderate hypothermia in the management of severe liver hemorrhage requiring temporary occlusion of blood flow. PMID- 1740802 TI - Results of a multi-institutional outcome assessment: results of a structured peer review of TRISS-designated unexpected outcomes. AB - The utility of TRISS as a component of trauma center quality assurance (QA) was evaluated. TRISS survival probabilities were estimated for a total of 2,023 consecutive trauma patients admitted to three level-I trauma centers during a 6 month period. A structured peer review was performed of the 50 patients (2.1%) having statistically unexpected outcomes. For 23 (18 survivors, five deaths) TRISS-designated outcomes were sustained in peer review. In 27 cases (one survivor, 26 deaths) TRISS-designated outcomes were not sustained by peer review and TRISS. Limitations were identified in each case. Peer review of unexpected outcomes identified by TRISS provided a consistent and objective QA methodology. An understanding of TRISS as an objective component of the trauma center QA process is essential in blending it with what is, at present, a largely subjective process in many hospitals. Use of TRISS standardizes the peer review process, resulting in a more reliable base for development and improvement of trauma center QA programs. PMID- 1740803 TI - Use of skin staplers in experimental gastrointestinal injuries. AB - Undocumented reports exist concerning use of skin staplers to close small perforations of the gut. This study examined use of this device in experimental gastrointestinal injuries in dogs. In 18 anesthetized mongrel dogs, matching uniform perforations were made with a sterile leather punch; one perforation of each pair was closed with 3-0 silk and the other with a skin stapler. A total of 80 stomach, 238 small intestine, and 140 colon perforations were created. Hole sizes progressed from 1.9 to 5.0 mm. Unrepaired intestinal wounds leaked and were lethal. No leaks were identified in wounds closed with either sutures or staples provided that closure was complete. Speed of staple closure was faster than that of suture closure (1.2 vs. 16.0 seconds), but ease of closure was similar. It is concluded that skin staplers are safe for repair of small wounds, created under ideal conditions, in canine gastrointestinal tracts. Similar injuries in traumatized humans deserve study, but existing skin staplers may be ineffective for human intestine since gut wall thickness in humans is less than that in dogs. PMID- 1740804 TI - Guaiac testing in the diagnosis of rectal trauma: what is its value? AB - Rectal examination with guaiac testing is a standard part of the emergency department evaluation of acutely traumatized patients. Its major role is in the recognition of occult bowel injury. We questioned its efficacy in detecting occult rectal injury in patients with penetrating trauma. We reviewed the charts of 19 patients with suspected rectal injury. Ten injuries were to the abdomen, nine to the buttock, and three to the thigh. Guaiac testing was 69% (11/16) sensitive and 33% (1/3) specific. Rigid sigmoidoscopy was 100% (12/12) sensitive and 67% (2/3) specific. Sensitivity was 100% (8/8) when the two were combined. Our findings suggest that guaiac testing is not accurate enough to rule out the presence of occult rectal injury. The result of guaiac testing must not influence the decision to further evaluate patients with high-risk injuries. PMID- 1740805 TI - Blunt trauma during pregnancy: factors affecting fetal outcome. AB - During a 9 1/2-year period, 76 pregnant women who sustained blunt trauma were admitted to a level-I trauma center. Fetal outcome was ascertained in 59 patients (78%). Successful delivery was noted in 35 patients (46%). Eight patients (11%) elected to undergo abortion for nonmedical reasons. Sixteen patients (21%) sustained fetal loss, and 17 patients (22%) were lost to follow-up. The 51 patients who either delivered successfully or experienced a fetal loss were studied to determine the factors that affected fetal outcome. Variables analyzed included gestational age and maternal age, Glasgow Coma Scale score, serum bicarbonate level, pH, PCO2, PO2, blood pressure, heart rate, Injury Severity Score, and performance of surgery or diagnostic peritoneal lavage. Logistic regression analysis revealed that ISS (p less than 0.01) and admission serum bicarbonate level (p less than 0.02) have the most significant correlation with fetal outcome. No other variable exhibited a statistically significant influence on fetal outcome. This information documents that fetal demise is related to severity of maternal injury as characterized by ISS. A low serum bicarbonate level corresponds to maternal hypoperfusion and hypoxia, which may be otherwise unrecognized because of the normal physiologic changes occurring during pregnancy. Based on these findings, routine serum bicarbonate determination in all pregnant patients being evaluated for trauma is advocated. Performance of DPL and surgery do not have a significant association with fetal loss and therefore should not be withheld when indicated in a pregnant patient. PMID- 1740806 TI - The pre-Medicare role of city/county hospitals in education and health care. PMID- 1740807 TI - Will future surgeons be interested in trauma care? Results of a resident survey. AB - Advanced-level general surgery residents were surveyed about their interest in providing trauma care upon completion of their residency training. Questionnaires were sent to 1,795 residents and 886 (49%) replied. Two thirds of the residents stated that trauma was a rewarding field, but only 18% wanted it as a career or as a major part of their practice. The interest in trauma fellowships was also very low. Disaffection with trauma care was predominant in the survey. Primary reasons for these negative feelings were the large amount of nonoperative care rendered in treating blunt trauma patients and the unsavory type of patients encountered with most penetrating trauma injuries. Lifestyle issues were important but were not rated as high as other factors. Complaints about the structure of current trauma rotations in many institutions and the negative impact of many trauma surgeons as role models were frequently cited as reasons for respondents not pursuing trauma care as a career interest. PMID- 1740808 TI - Pre-existing disease in trauma patients: a predictor of fate independent of age and injury severity score. AB - Improvement in trauma management requires a better understanding of the effect of a patient's preinjury health status on outcome. Specific historical findings and laboratory criteria were used to define pre-existing disease (PED) states and determine if they were independent predictors of fate in trauma victims. Of 7,798 adult patients admitted to a level I trauma center from July 1986 through June 1990, 16.0% (1,246) had greater than or equal to 1 PED. The PED+ and PED- patients had no significant difference in Injury Severity Scores (ISSs) (15.7 versus 15.6) and admission Glasgow Coma Scale (GCS) scores (13.9 versus 13.8). The PED+ patients were older (49.2 versus 30.6 years) (p less than 0.001) and had a higher mortality rate (9.2% versus 3.2%) (p less than 0.001) than PED- patients. Mortality rates were also elevated for patients with greater than or equal to 2 PEDs (18%) and for those with renal disease (38%), malignancy (20%), and cardiac disease (18%) (p less than 0.001) compared with PED- patients. Controlling for age and ISS, there was an association between PED and mortality (Mantel-Haenszel p less than 0.03). Multivariate regression showed that PED is an independent predictor of mortality (R2 = 0.1918; p less than 0.0001). The greatest increases in mortality were found among patients less than 55 years and with ISS less than 20. Changes in prehospital triage criteria and outcome scoring are needed. Improvements in the management of trauma victims with chronic disease may decrease their mortality rate. PMID- 1740809 TI - Splint appliance for the management of posttrauma lip deformities: technical note and case reports. AB - Trauma sustained to the commissures of the lips will result in perioral tissue deficits. Without intervention, this will lead to functional and esthetic deformities. Splinting devices have proven to be an effective and economical means of treatment. Reviews have appeared in the literature describing techniques and treatment regimens for the use of such oral commissure splints. Each has specific advantages and disadvantages in application. A variation of these previously described splints now in use at the University of Chicago Hospitals is presented. Three case histories are presented with discussion of the uses and advantages of this appliance. PMID- 1740810 TI - Parasymphyseal fracture with an associated temporomandibular joint dislocation: case report. AB - A case of traumatic mandibular fracture with associated unilateral anterior dislocation of the temporomandibular joint in a child is described. Although anterior dislocation is common, this combination of fracture and separate dislocation to our knowledge has not been reported in a young child. The unusual management required in this case is discussed. PMID- 1740811 TI - Traumatic bilateral renal artery thrombosis diagnosed by computed tomography with successful revascularization: case report. AB - Traumatic bilateral renal artery thrombosis is a rare injury. We found 15 cases previously reported. An additional case report of a 54-year-old man is presented with a review of the literature. The diagnosis was made by computed tomography and confirmed by angiography. Successful revascularization was performed. A high index of suspicion, early diagnosis, and prompt revascularization are essential in obtaining optimal results without hypertension or permanent impairment of renal function. PMID- 1740812 TI - Pathologic consequences of bilateral pulmonary lower lobectomies: case report. AB - Most injuries to the lung can be managed nonoperatively and rarely require resection. A case of bilateral hilar injuries requiring bilateral pulmonary lower lobectomies is presented. The resulting pulmonary hypertension, right ventricular failure, and cardiogenic shock explain the high mortality following extensive pulmonary resection in thoracic trauma and support the concept of a conservative approach. PMID- 1740813 TI - Intensity and efficiency of transmission and the development of microfilaraemia and disease: their relationship in lymphatic filariasis. AB - Currently available methods for measuring the intensity of transmission in the lymphatic filariases are all to some extent unsatisfactory. Clinical methods for defining the presence of filarial disease are also less than perfect, and many infected persons remain free of symptoms and signs for very long periods. Incidence rates of microfilaraemia calculated from prevalence rate data are combined with 'entomological inoculation rates' obtained by direct observations of vector landing rates, infective larval rates and infective larval densities in field studies to determine efficiencies of transmission, and to relate transmission parameters to observed microfilarial and disease prevalence rates. Published studies from various endemic areas of the world which provide sufficient data have been analysed, using reversible catalytic models. In general, it seems that much less intense levels of transmission are needed in sub Saharan Africa to produce given rates of microfilaraemia and disease than in Asia and Oceania, in the case of Wuchereria bancrofti infections; similarly, the genus Anopheles appears to produce infection and disease much more efficiently than the genera Culex and Aedes when transmitting W. bancrofti. The only example of Brugia malayi transmitted by Mansonia spp. analysed provided the highest level of transmission efficiency found. Tolerable levels of transmission analogous to those used in onchocerciasis cannot at present be defined for the lymphatic filariases; it seems that the intensity of transmission required to produce new cases of disease is probably below that required to produce new cases or episodes of readily detectable microfilaraemia. PMID- 1740814 TI - An investigation of some risk factors for severe leptospirosis on Barbados. AB - Between November 1979 and the end of December 1986 (7.17 years), 248 cases of leptospirosis were confirmed among hospital patients on Barbados (mean 35 per year; range 25-57). Considering the 235 who were greater than or equal to 15 years of age, the annual incidence of leptospirosis was 19.2/100,000 population (14.0 for all age groups). There were 173 males and 62 females, and for cases aged 15-34 leptospirosis was 9.6 times more common in men than women. Among men, incidence increased fairly steadily with age, and an even steadier increase was apparent in women up to age 64, with some decline in later years. The incidence of disease was much higher among agricultural than other workers and the non employed. Highest case numbers were recorded in the parishes of St Michael (65 or 28%) and Christ Church (36 or 15%), though the incidence was lowest in these two parishes (13.1/100,000 and 17.4/100,000, respectively). The highest incidence rates were in St Andrew and St Joseph (50.2 and 36.1/100,000, respectively). The incidence in areas with rainfall greater than or equal to 1600 mm (32.6/100,000) was nearly twice that in areas with rainfall less than 1600 mm (17.3/100,000). There is a clear link between cases of severe disease and recent rainfall. Using 134 patients greater than or equal to 15 years of age with fever due to other illnesses as controls, a higher proportion of cases than controls came from rural areas. The risk of contracting leptospirosis was increased for all categories of manual workers relative to the group at lowest risk (non-manual indoor workers). Sugar-cane workers were five times more likely to contract leptospirosis than were non-manual indoor workers, while those whose families minded livestock were 2.5 times more likely, and those with rodents in their garden/yard were 1.8 times more likely to do so. Other risk factors examined did not show significant associations with the disease. Despite increasing mechanization and the use of more protective clothing, agricultural workers are still at high risk from leptospirosis. The annual range of cases is likely to stay much as it is in the foreseeable future. PMID- 1740815 TI - Pattern of road traffic accident cases in a Nigerian university teaching hospital between 1987 and 1990. AB - This retrospective study was undertaken to obtain recent information on the pattern of road traffic accidents (RTA) and the associated disabilities in Nigeria. We reviewed the medical records of RTA related cases recorded between 1987 and 1990 at Obafemi Awolowo University Teaching Hospital, Ile-Ife. Over the 4-year period, 2667 cases of RTA were recorded and this constitutes 5.3% of the total medical and surgical emergencies seen at the hospital. Furthermore, RTA cases accounted for 8.1% (range = 1.3-29.30%) of the total medical and surgical emergency deaths. Only 353 (13.2%) of the total number of RTA cases required hospitalization. About 12.7% of the patients spent less than 2 days in the hospital while 24.6% of the patients were hospitalized for more than 2 months. The 20-40 years age group recorded the highest incidence of RTA requiring hospitalization and males were twice as prone to RTA as females. Pedestrian casualties accounted for 28.3% of the RTA cases. The majority (67.4%) of the hospitalized RTA patients sustained a fracture and 12.2% died during admission. Our findings if extrapolated to all the hospitals in Nigeria confirm the speculation that RTA is one of the leading causes of death in Nigeria. PMID- 1740816 TI - Role of atropine in management of cardiovascular manifestations of scorpion envenoming in humans. AB - We undertook a retrospective analysis of 35 victims of red scorpion (Mesobuthus tamulus) sting, admitted to our hospital in Mahad, Maharashtra State, India. Increase in duration as well as severity of clinical signs, including myocardial injury and poor response to conventional treatment, were observed in 17 victims treated with atropine compared to another 18 victims who were not so treated. We do not advocate routine use of atropine to block transient cholinergic effects of scorpion envenoming. PMID- 1740817 TI - The prevalence and environmental risk factors for moderate and severe trachoma in southern Ethiopia. AB - Inflammatory eye disease is a leading cause of reported morbidity throughout rural Ethiopia. The purpose of this investigation was to document the prevalence of trachoma at all stages and to identify environmental risk factors for moderate to severe cases among rural inhabitants of Sidamo Region in southern Ethiopia. An ophthalmic examination followed by a blind household interview were completed on 1222 randomly selected subjects. Those with moderate or severe trachoma were compared with normal subjects for rates of exposure to potential environmental risk factors. The results of the eye examinations are as follows; normal 59.5%, trivial 8.4%, mild 10.3%, moderate 8.5%, severe 8.0%, cicatricial 3.0%, and other eye diseases without trachoma 2.3%. Highest prevalence rates for moderate to severe trachoma were found in those under 10 and over 45 years of age. Increased adjusted odds ratios were found for exposure to garbage disposal near home, crowded sleeping arrangements, animals inside the home, cooking in a separate room, and living at lower altitudes. The identification of several modifiable environmental risk factors for trachoma will be of use in the further development of preventive programmes. PMID- 1740818 TI - Tropical pyomyositis in India: a clinico-histopathological study. AB - Eighteen cases of tropical pyomyositis, aged 12-45 years, were seen over a 3-year period. There was clustering of cases in January, February and July to October. Male:female ratio was 14:4. Multiple muscular lesions (greater than 2) were common (67%). Extramuscular complications were present in 50% of the cases. Cardio-pulmonary involvement was most frequent. Muscle biopsies, done in 16 cases, showed suppurative changes (pus) in 15 cases and one case of non suppurative myositis. Muscle necrosis, cellular infiltration with polymorphs and haemorrhage in-between muscle fibres were common. PMID- 1740819 TI - Evaluation of fractionated circulating filarial antigen in diagnosis of bancroftian filariasis. AB - Circulating filarial antigen (CFA) isolated from the plasma of microfilaraemic patients was fractionated on an Ultrogel ACA 34 column. The second protein peak (CFA2) showing filarial antigen was further fractionated by DEAE-cellulose column chromatography into two fractions (CFA2 DE1 and DE2). CFA2 DE1 fraction, showing antigenic activity, was further evaluated in an ELISA for its diagnostic use in bancroftian filariasis. Studies with CFA2 DE1 and anti-CFA2 DE1 antibody showed that they were highly active in the detection of filarial antibody and antigen in asymptomatic microfilaraemia sera and thus obviate the need for the tedious night blood collection and examination. Fractionated filarial plasma can be another candidate antigen for immunodiagnosis of bancroftian filariasis. PMID- 1740820 TI - Evaluation of an enzyme linked immunosorbent assay (ELISA) using Schistosoma mansoni soluble egg antigen as a diagnostic tool for Schistosoma mansoni infection in Ethiopian schoolchildren. AB - Evaluation of the performance of an ELISA test using S. mansoni soluble egg antigens (SEA) in relation to the standard parasitological diagnostic procedure (Kato) was conducted in a specially set up study on 400 Ethiopian schoolchildren. Faecal samples were collected on 3 successive days for preparation of Kato thick smears and two finger prick blood samples were collected onto filter paper from all the children on day 1. All helminth ova present in the triplicate Kato slides were counted and the ELISA test was carried out on both eluted serum samples. Prevalence of infection by Kato was 83.5% in the endemic area and the sensitivity and specificity of the ELISA test were 97.6% and 30.3% respectively, whereas the specificity of the ELISA in the non-endemic area was 95.5%. The main cause of 'false positivity' in the endemic area appeared to be inapparent S. mansoni infection. Because of its high sensitivity, this ELISA test will clearly be of value for seroepidemiological surveys. PMID- 1740821 TI - Hospital-based study on neonatal tetanus, Buluba Hospital, 1985-1989. AB - Neonatal tetanus is a major cause of morbidity and mortality among neonates in Uganda. A retrospective study has been made of 228 cases of neonatal tetanus seen in Buluba Hospital over the 5-year period of 1985-1989. The number of cases of neonatal tetanus admitted per year to the hospital did not decrease significantly during that period suggesting that the immunization programme aimed at immunization of pregnant women with tetanus toxoid has not had a clear impact. Over 40% of neonatal tetanus cases came from the two nearest subcounties: Waina and Imanyiro. Over 75% of admitted cases of neonatal tetanus accounted for 23% of all deaths among child admissions. More than 90% of neonatal tetanus cases showed the first symptoms of the illness within the first 14 days of life; the shortest incubation period was 2 days. The average age at onset was 5.6 days and the average age at death was 9.9 days. The need for a more effective immunization programme and more intensified activities to increase the proportion of deliveries attended by trained personnel and improve hygienic conditions during and after deliveries is emphasized. PMID- 1740822 TI - False positive serology for visceral leishmanias (kala-azar) using the indirect haemagglutination (IHA) method. AB - Persistent false serology for kala-azar using the indirect haemagglutination technique is described in two patients. One patient had Behcet's disease and the other infective endocarditis. PMID- 1740823 TI - Cytodiagnosis of rhinosporidiosis. AB - Two clinically suspected cases of nasal rhinosporidiosis were studied cytologically using a wipe out technique. The smears showed the typical spores of the fungus and the cytological diagnosis of rhinosporidiosis was confirmed by excisional biopsy. The smear is recommended as a routine preliminary screening technique in the diagnosis of suspected cases of rhinosporidiosis. PMID- 1740824 TI - Gangrenous cholecystitis due to hepatitis A infection. AB - A 6-year-old boy was admitted to hospital with acute gangrenous cholecystitis requiring emergency cholecystectomy. Examination of the gall-bladder revealed severe inflammation with areas of necrosis and mucosal sloughing; serology confirmed hepatitis A infection. Acute cholecystitis due to hepatitis A infection has very rarely been reported. PMID- 1740825 TI - Health and population data for developing countries available through USAID project. PMID- 1740826 TI - The efficacy of Doppler umbilical artery velocimetry in identifying fetal acidosis. A comparison with fetal biophysical profile. AB - In 105 singleton pregnancies in which cesarean section was performed before the onset of labor, the efficacy of Doppler umbilical velocimetry in identifying fetal acidosis was determined and compared with fetal biophysical profile. Doppler velocimetry showed a significant correlation with the umbilical artery pH and was also a sensitive indicator of fetal acidosis, comparable to the biophysical profile score. Patients were classified into four groups. Groups with abnormal Doppler results showed a significantly higher prevalence of fetal acidosis, and all the fetuses with abnormal Doppler results were either in acidosis or in a growth-retarded state. Our data lend further support to the clinical validity of Doppler umbilical velocimetry in identifying fetal acidosis or compromise. PMID- 1740827 TI - Method for determining the SATA and SAPA intensities for real-time ultrasonographic scanning modes. AB - Determination of a complete set of sonographic exposure parameters is desirable for any clinical ultrasound unit and is particularly important in controlled studies of biologic effects. When the exposure system is a diagnostic real-time scanner operating in autoscan mode, the determination of two of these parameters, the spatial average-temporal average (SATA) and the spatial average-pulse average (SAPA) intensities, is not straightforward because of the spatial overlap of successive propagating pulses. A method is described for determining these intensities for autoscan operation. The primary tool in the method is a digital oscilloscope, which supports pretrigger recording and configuring of the oscilloscope's memory into segments that can record rapidly occurring successive pulses, each segment recording one pulse. Results for a few commercially available real-time scanning systems are presented. PMID- 1740828 TI - The fetal thyroid: normal and abnormal sonographic measurements. AB - The thyroid of 31 fetuses at low risk for perinatal thyroid disease were evaluated sonographically. The transverse width and circumference of the fetal thyroid was measured prospectively to provide normative values for each gestational age. In addition, the thyroid of 23 fetuses at risk for thyroid disease were examined sonographically and compared to the control group. At birth, 18 of the neonates had no evidence of thyroid dysfunction, whereas 5 newborns had goiters and abnormal thyroid function. The fetal thyroid measurements for these 5 neonates were above the upper limit of the 95% confidence interval compared to the control group. The other 18 fetuses in the group at risk for thyroid disease but without evidence of thyroid dysfunction at birth had fetal thyroid measurement within the normal range. PMID- 1740829 TI - Placenta accreta. Additional sonographic observations. AB - Recent reports describe the antenatal sonographic diagnosis of placenta accreta based on failure to visualize a hypoechoic zone at the placental margin. This finding was confirmed in our series of seven cases. New observations in this series include prominent large or multiple placental venous lakes and periuterine vascularity in six of seven cases, and progressive thinning and disappearance of the retroplacental hypoechoic zone on sequential examinations in two of seven cases. Loss of normal venous flow pattern on Doppler interrogation of the peripheral placental margin also appeared to be of value in two patients. Histologic correlates for these findings are suggested on the basis of the primary histopathologic feature of placenta accreta: deficiency of the decidua basalis. Differential diagnostic considerations, including abdominal pregnancy and trophoblastic disease, also are discussed. PMID- 1740830 TI - Ultrasonography of cystic parotid lesions in HIV infection. Similarity of sonographic appearance with Sjogren's syndrome. AB - Bilateral cystic parotid glands occur in some cases of human immunodeficiency virus (HIV) infection. This abnormality, which is associated with cervical adenopathy, can be defined by sonography in the superficial gland, as noted in three men. In retrospect, this parotid disease has similarity to the sonographic finding of Sjogren's syndrome, except for the finding of cervical adenopathy, an observation not previously appreciated. PMID- 1740831 TI - Color Doppler imaging in the assessment of uteroplacental blood flow in abnormal first trimester intrauterine pregnancies. An attempt to define etiologic mechanisms. AB - The addition of color Doppler imaging (CDI) to the vaginal probe now enables sonographers to study more accurately the maternal-fetal circulation at the early stages of the gestation. Doppler studies of normal intrauterine first trimester gestations have been published, and our investigation was an attempt to study uteroplacental blood flow in abnormal intrauterine first trimester gestations. Although the calculated indices did not differ significantly from those found in normal gestations, we did find a higher rate of color detection in gestations defined as anembryonic as compared to those defined as missed abortions. Circulation abnormalities probably play a significant role in early pregnancy failures, and we believe CDI will help define the different etiologic mechanisms causing these early complications. PMID- 1740832 TI - Duplex and color Doppler appearance of isolated internal iliac aneurysm. PMID- 1740833 TI - Congenital syphilis associated with dilation of fetal small bowel. A case report. PMID- 1740834 TI - Prenatal diagnosis of vestigial tail. PMID- 1740835 TI - Early diagnosis of holoprosencephaly. PMID- 1740836 TI - Endosonographic diagnosis of a submucosal gastric cyst. PMID- 1740838 TI - When sports and HIV share the bill, smart money goes on common sense. PMID- 1740837 TI - Sonographic demonstration of air in the myometrium. A complication of culdocentesis. AB - Six cases are presented in which air was seen in the myometrium in the distribution of the arcuate vessels during sonography performed after culdocentesis to exclude ectopic pregnancy. Three of these patients had viable intrauterine pregnancies; the others had an incomplete abortion, a complete abortion, and a right ectopic pregnancy. This relatively rare complication of culdocentesis should be kept in mind, especially when scanning patients with suspected inflammatory process of the uterus, so as not to confuse air in the arcuate vessels with a uterine abscess. PMID- 1740839 TI - World Health Organization consensus statement--consultation on AIDS and sports. PMID- 1740840 TI - Like attacker probing defenses, cholera threatens US population from elsewhere in this hemisphere. PMID- 1740841 TI - From the National Institutes of Health. PMID- 1740842 TI - From the Centers for Disease Control. Cholera associated with imported coconut milk. PMID- 1740844 TI - From the Centers for Disease Control. Eastern equine encephalitis virus--Florida, 1991. PMID- 1740843 TI - From the Centers for Disease Control. Public health assessment--Russian Federation. PMID- 1740845 TI - A piece of my mind. What we fail to see. PMID- 1740846 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1740847 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1740848 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1740849 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1740850 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1740851 TI - Turning the tables on probe pressures--go with the flow, abandon the scan? PMID- 1740852 TI - Turning the tables on probe pressures--go with the flow, abandon the scan? PMID- 1740853 TI - Gender rears its ugly head again. PMID- 1740854 TI - Left-handedness in male-to-female transsexuals. PMID- 1740855 TI - Pedestrian and hypothermia deaths among Native Americans in New Mexico. Between bar and home. AB - OBJECTIVE: To determine the nature of excess injury mortality among Native Americans in New Mexico. DESIGN: Retrospective review of death certificates for deaths from unintentional injuries. SETTING: The state of New Mexico. SUBJECTS: New Mexico residents who died of unintentional injuries between January 1, 1980, and December 31, 1989. MAIN OUTCOME MEASURE: Cause-specific mortality rates. RESULTS: Over half of the excess mortality from all unintentional injuries among Native Americans resulted from hypothermia and from pedestrian-motor vehicle crashes. New Mexico Native Americans were nearly eight times more likely to die in pedestrian--motor vehicle crashes and were 30 times more likely to die of hypothermia compared with other New Mexico residents. At death, 90% of those Native Americans tested were highly intoxicated (median blood alcohol concentrations of 0.24 and 0.18 g/dL [corrected] for pedestrian and hypothermia deaths, respectively). Despite the fact that most Native Americans in New Mexico live on reservations, most deaths occurred at off-reservation sites in border towns and on roads leading back to the reservation. CONCLUSIONS: The possession and sale of alcohol is illegal on many Native American reservations. This policy forces Native Americans who want to drink to travel long distances to obtain alcohol. These data suggest that this policy is also the likely explanation for the markedly increased risk of death from hypothermia and pedestrian-motor vehicle crashes in this population. PMID- 1740856 TI - Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute. AB - OBJECTIVE: After an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (LCMV) infections among the institute's employees and to identify risk factors for infection. DESIGN: Retrospective cohort study. SETTING: A US cancer research institute. PARTICIPANTS: Eighty-two of 90 institute employees. MAIN OUTCOME MEASURES: Serum LCMV antibodies. RESULTS: Seven workers (9%) with definite LCMV infection (LCMV IgG antibody titer greater than or equal to 16) and one worker (1%) with probable infection (IgG titer = 8) were identified (10% overall seroprevalence). All infected employees handled animals or animal tissues and were more likely than other animal handlers to have worked with nude mice (Mus musculus) (P less than .02). Among the 31 employees who worked with nude mice at the institute, infected workers were more likely to clean the cages of nude mice (P much less than .001), change their bedding (P less than .01), and change their water (P less than .001). The institute had been injecting nude mice with LCMV-infected tumor cell lines and had recently increased the nude mouse population and the duration of experiments. These changes would have increased the LCMV burden at the facility and were temporally associated with the cluster of LCMV infections in employees. CONCLUSIONS: This LCMV outbreak, the first reported since 1974, is the first associated with nude mice. It illustrates the ongoing hazard LCMV poses in research laboratories. Since the symptoms of LCMV infection can be nonspecific, clinicians should consider this diagnosis in ill patients who report laboratory rodent exposure. PMID- 1740857 TI - Infections complicating mycosis fungoides and Sezary syndrome. AB - OBJECTIVE: To determine, in patients with mycosis fungoides and Sezary syndrome, the incidence of infections, the importance of nosocomial infections, and the epidemiologic factors associated with cutaneous and visceral infections. DESIGN AND SETTING: Retrospective inception cohort study at a university medical center referral clinic. PATIENTS: Three hundred fifty-six patients with mycosis fungoides or Sezary syndrome. MAIN OUTCOME MEASURES: Incidence rates for specific infections, and multivariate risk ratios for demographic and clinical factors associated with infection. RESULTS: Cutaneous bacterial infection was most common (17.0 infections per 100 patient-years), followed by cutaneous herpes simplex virus and herpes zoster virus infection (3.8 infections per 100 patient-years), bacteremia (2.1 infections per 100 patient-years), bacterial pneumonia (1.7 infections per 100 patient-years), and urinary tract infection (1.4 infections per 100 patient-years). Twenty-seven percent of herpesvirus infections disseminated on the skin but none disseminated to internal organs. Pneumonia or bacteremia was present in 88% of patients who died of infection. Only three patients had invasive fungal or protozoal infection. Nosocomial infections accounted for 19% of cutaneous bacterial infections, 59% of bacteremias, 62% of pneumonias, and 88% of infections leading to death. By logistic and Cox regression, the presence of extracutaneous involvement with lymphoma was the most important independent risk factor for recurrent bacterial skin infection (risk ratio [RR], 12; 95% confidence interval [CI], 1.2 to 120), disseminated herpesvirus infection (RR, 28; 95% CI, 2.7 to 290), bloodstream infection (RR, 5.5; 95% CI, 1.7 to 18), and death from infection (RR, 15; 95% CI, 3.6 to 64). CONCLUSIONS: Community-acquired bacterial skin infections are a common cause of morbidity in patients with mycosis fungoides and Sezary syndrome but are usually treated without hospital admission. Bacteremia and pneumonia, which are usually nosocomial, are the major infectious causes of death. Advanced disease stage, independent of corticosteroids and other therapies, is the most important risk factor for both cutaneous and systemic infections. PMID- 1740858 TI - Factors that prompted families to file medical malpractice claims following perinatal injuries. AB - OBJECTIVE: To identify self-reported reasons that prompt families to file malpractice claims following perinatal injuries. DESIGN: Families were interviewed by telephone using a questionnaire that contained structured and open ended questions. PARTICIPANTS: Mothers of infants who had experienced permanent injuries or deaths and had closed malpractice claims in Florida between 1986 and August 1989 were interviewed. Questionnaires were completed by 127 (35%) of a total of 368 such families. OUTCOME MEASURES: Reasons prompting families to file and families' descriptions of medical events, advice from acquaintances, and the quality of physician-family communication. RESULTS: Families volunteered numerous reasons for filing: advised by knowledgeable acquaintances (33% of respondents), recognized cover-up (24%), needed money (24%), recognized that their child would have no future (23%), needed information (20%), and decided to seek revenge or protect others from harm (19%). Over one third of all families indicated that they were told by medical personnel prior to filing that the care provided had caused their children's injuries. Families expressed dissatisfaction with physician-patient communication. Families believed that physicians would not listen (13% of sample), would not talk openly (32%), attempted to mislead them (48%), or did not warn about long-term neurodevelopmental problems (70%). CONCLUSION: Families give many reasons for filing a claim. Obtaining money may not be the only goal for some families who file suit. PMID- 1740859 TI - Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. AB - OBJECTIVE: To determine central nervous system (CNS) involvement in acutely disseminated Borrelia burgdorferi infection by measurement of borrelia-specific DNA using the polymerase chain-reaction (PCR) assay and to compare the results of this with standard serological tests. DESIGN: Prospective study with laboratory investigators blinded to clinical data. SETTING: Multicenter office practice with a central reference laboratory. PATIENTS: Cerebrospinal fluid (CSF) was collected from 12 patients with acute disseminated Lyme borreliosis with less than 2 weeks of active disease. The normal control specimens came from 16 patients whose CSF samples had been sent to the clinical laboratory for tests unrelated to the present study. MAIN OUTCOME MEASURES: Clinical evidence of disease and laboratory abnormalities. RESULTS: Eight of the 12 patients (four of six with multiple areas of erythema migrans and four of six with cranial neuritis without erythema migrans) had B burgdorferi-specific DNA in their CSF. Among the 12 patients studied, nine had acute cranial neuritis and six had multiple erythema migrans lesions. Just four of the eight who were found to have spirochetal DNA in their CSF had complaints suggestive of CNS infection. In three of the PCR-positive CSF samples, no other abnormalities were noted. None of 16 samples from controls were positive in the PCR assay. CONCLUSION: B burgdorferi can invade the CNS early in the course of infection. Careful consideration should be given to choosing antibiotics that achieve adequate CSF levels in patients with disseminated infection. PMID- 1740860 TI - Early predictors of career achievement in academic medicine. AB - OBJECTIVE: To identify early personal and scholastic factors that predict academic career choice and long-term career achievement among academic physicians. DESIGN: A longitudinal cohort study. PARTICIPANTS: Nine hundred forty four male physicians who graduated from The Johns Hopkins University School of Medicine, Baltimore, MD, from 1948 through 1964. OUTCOME MEASURES: Career achievement outcomes included attained faculty rank in 1990 and the number of citations (20 to 24 years after graduation) to published work. RESULTS: Of the 944 physicians, 424 (45%) had chosen academic careers. Scholastic performance and research experience in medical school were independently associated with having chosen an academic career (P less than .001). Among academicians, higher attained rank in 1990 was independently associated with the following: (1) membership in Alpha Omega Alpha (relative risk [RR] = 4.94, P = .0001); (2) rank in the top third of the graduating class (RR = 2.68, P = .01); and (3) research experience in medical school (RR = 3.11, P = .0001). These three factors were also independently associated with more citations to participants' published work (P less than .05). CONCLUSION: These data suggest that scholastic performance and research experience during medical school predict career achievement in academic medicine over 20 years in the future. PMID- 1740861 TI - Achieving compliance with influenza immunization of medical house staff and students. A randomized controlled trial. AB - OBJECTIVE: To determine the optimal method to increase influenza immunization rates of medical house staff and students. DESIGN: Prospective randomized trial and cross-sectional survey. STUDY GROUP: Four hundred forty-two internal medicine, obstetrics-gynecology, and general surgery residents and junior medical students. MEASUREMENTS: The four interventions employed were (1) an educational memorandum outlining vaccine indications sent to all study group members, (2) a personal letter mailed to a random sample of half of the remaining unimmunized persons, (3) a telephone call to half of the unimmunized letter recipients, and (4) vaccine offered directly to the remaining unimmunized persons in clinics and conferences. In addition, a questionnaire was administered to all persons requesting or offered vaccine. MAIN RESULTS: During the 3 weeks after the memorandum, 87 (20%) of 442 persons were immunized. Five weeks after the letter, 61 (34%) of persons receiving a letter and 30 (17%) of the no-letter controls (P = .0005) had been immunized. After the telephone call, there was a statistically insignificant trend toward increased compliance. In clinics and conferences, 90% of persons reached were immunized and 10% refused, largely extinguishing the effect of prior interventions. At completion of the study, 275 (62%) of 442 participants were immunized, 29 (7%) refused, and 138 (31%) were not reached. Questionnaire results revealed that only 32% had ever been previously immunized against influenza, yet 70% stated that they had worked despite having influenzalike symptoms. CONCLUSION: A high rate of immunization of house staff and medical students can be achieved most effectively by offering vaccine in clinics and conferences. Continued education about influenza immunization is necessary for physicians and medical students. PMID- 1740862 TI - Current perspective on Lyme borreliosis. PMID- 1740863 TI - Alcohol-related deaths of American Indians. Stereotypes and strategies. PMID- 1740864 TI - Epidemic cholera in Latin America. PMID- 1740865 TI - Unilateral vocal cord paralysis. PMID- 1740866 TI - A 38-year-old female trauma victim of a car bomb. AB - This case profoundly affected prehospital and hospital care providers alike. Most Midwestern areas have small cities and towns, and most of our trauma results from accidents, not deliberate, senseless human acts. There is a quality of life in our community that does not involve doing things like this to others. If our staff was this affected, it is sobering to think of the profound adjustment required of the victim. PMID- 1740867 TI - Working with battered women in the emergency department: a model program. AB - WomanKind, Inc., can be a prototype for every emergency department in every hospital across the country. Program services and delivery can be modified to fit the needs and resources of any facility. The mandate is to begin to address the underlying causes of ED visits by battered women. PMID- 1740869 TI - The Hennepin County Medical Center's Women's Advocacy Program--sixteen years of service. PMID- 1740868 TI - Attitudes of emergency nurses before and after a 60-minute educational presentation on partner abuse. PMID- 1740871 TI - Guidelines for intervention by ED nurses in cases of domestic abuse. PMID- 1740870 TI - Initial nursing impression in patients with chest discomfort. PMID- 1740873 TI - Introducing ENF: a foundation for our profession. PMID- 1740872 TI - A 2-year-old with an altered level of consciousness: case review and differential diagnosis. PMID- 1740874 TI - An assessment of categories of illness and injury among patients seen at and admitted to an Australian city hospital. PMID- 1740875 TI - Development of the ENA National Standard Guidelines for Prehospital Nursing Curriculum. PMID- 1740876 TI - The National Standards Guidelines for Prehospital Nursing Curriculum: a job well done. PMID- 1740877 TI - The emotional trauma of miscarriage in the emergency department: a first-person account. PMID- 1740878 TI - Recollections of an American nurse in Riyadh during the Persian Gulf War. PMID- 1740879 TI - Respiratory syncytial virus (RSV): a common health problem. AB - RSV infections pose a variety of considerations for emergency personnel. Nurses should be suspicious of this cause of illness during the winter months because of its prevalence, should be able to recognize and treat those who are experiencing or are at risk for acquiring lower respiratory tract complications, and should be aware of the need to reduce the spread of the virus by using isolation techniques, vigorous hand-washing protocol, and other protective measures to reduce contact with the organism. Patients who are at high risk for respiratory distress should be admitted for observation and supportive therapy. PMID- 1740880 TI - ED visitor policies sought. PMID- 1740881 TI - School of nursing seeks ideas for developing ED clinical nurse specialist program. PMID- 1740882 TI - A successful bimonthly series of trauma case presentations conducted by primary nurses. PMID- 1740883 TI - Tips on nursing care of the pediatric organ recipient in the emergency department. PMID- 1740884 TI - Clinical clearance of the cervical spine. PMID- 1740885 TI - Announcing the trauma nursing resource document. Emergency Nurses Association. PMID- 1740886 TI - An 11-month-old with unexplained respiratory distress. PMID- 1740888 TI - The right time to share. PMID- 1740887 TI - HIV positive: the story of one "ordinary" emergency nurse. PMID- 1740889 TI - Correction to triage decisions column on Lyme carditis. PMID- 1740890 TI - More on pediatric nursing continuing education. PMID- 1740891 TI - Death washed by me. PMID- 1740892 TI - Leadership in nursing. PMID- 1740893 TI - Learning leadership through a community program. PMID- 1740894 TI - Classic leadership theories and roles. PMID- 1740895 TI - Leadership is changing, are you? PMID- 1740896 TI - The Zimmermann-Laband syndrome. AB - We report on two patients who exhibit the typical features of the rare Zimmermann Laband syndrome such as gingival fibromatosis, swelling of perioral tissues, nail hypo/aplasia, and abnormalities of terminal phalanges. The older patient suffers from epileptic seizures and shows osseous mandibular hypertrophy, two maxillary mesiodentes and lumbar spondylodysplasia. In the 2nd patient, a 3 year old male, the characteristic morphological features are already present. PMID- 1740897 TI - [Necrotizing enterocolitis--analysis of a case cohort]. AB - During a period of 25 months 11 newborns treated at the children's university hospital of Munster (0.8%) underwent laparotomy for necrotizing enterocolitis (NEC). The cases appeared sporadically without forming "clusters" typical of infectious etiology. 10 of 11 cases were premature infants (median birth weight 1280 g) stressing the predisposing role of immaturity. Ischemic events occurred in all patients prior to the onset of symptoms. The introduction of surfactant therapy during the study period did not influence the incidence apparently. Ultrasonography was superior to radiology with regard to detection of extraluminal gas. We differentiated two types of clinical courses (3 acute and 8 protracted). In 5 cases we noticed a relapse of clinical symptoms after uptake of oral feeding. 3 newborns died with septic shock. The median hospitalisation time was 88.5 days in the 8 survivors. Enterostomy was replaced by definite anastomosis after 67.5 days (median). Median daily weight gain was 16.6 g. Late complications like permanent stenoses of short bowel syndrome were not observed. Early surgical intervention according to the general rules of abdominal surgery seems important even in very low birth weight infants. PMID- 1740898 TI - [Retrospective study of 160 children with febrile convulsions]. AB - In a retrospective study of 411 children with cerebral convulsions over a period of 4 years, 160 patients with febrile seizures were found. This group consisted of 94 boys and 66 girls. The main purpose of this study was to establish the age of the first convulsive fit in each child. Febrile convulsions started in the first half year, increased in the second half year and culminated in the second year of life. This age dependent appearance was explained with passive immunization by maternal antibodies so that febrile convulsions appear when these antibodies decrease. The first occurrence of febrile convulsions appeared on an average of 22.9 months, in children with recurrent febrile convulsions a little earlier with 18.2 months. The most interesting fact was that children with a family history of febrile seizures showed an even earlier occurrence of the first seizure with 14.5 months. This tendency of early incidence of febrile convulsion in the group with family history and in the group of recurrent febrile convulsions could be shown as statistically significant respectively nearly significant in comparing with the group of retarded patients. A peculiar tendency for febrile convulsions seems to be documented by recurrent seizures in the patient himself, but also by a history of febrile convulsions in other family members. Both facts may lead to a very early incidence of febrile convulsions. PMID- 1740899 TI - [Psychomotor development of newborn infants at risk with reference to the neuron specific enolase]. AB - In a prospective study the psychomotor development of an unselected collective of risk newborn infants up to the end of the second year of life was examined. 199 children have developed normal, 21 showed developmental abnormalities, 84 light to moderate disturbances, and 30 severe disabilities. Already in the newborn period the concentration of neuron-specific enolase in the serum was evaluated. The NSE could be an indicator of brain damage. The determined values of NSE showed a log-normal-distribution at the three times (cord-blood, first or second day of life, third or fourth day of life, and ninth to eleventh day of life). Significant relationship between the psychomotor development during the first two years of life and of NSE-concentration was not found. Nevertheless the diagnostic value of the NSE is better with a specificity of 47.7% and a sensitivity of 80.0% than those of the results of intracranial ultrasound examination or of the erythrocytic-density-test. In contrast to these results the use of the neuron specific enolase alone for the prediction of individual prognosis of children is not be recommended. PMID- 1740900 TI - [Elimination of fat emulsions of various concentrations from the blood. Observational study in the intravenous administration of Lipovenos 10% and 20% in premature infants with very low birth weight]. AB - Within the scope of an observation study 40 premature low birth weight infants requiring parenteral nutrition received either 10% or 20% lipid emulsions (Lipovenos) for 7 days. The 10% lipid emulsion differs from the 20% lipid emulsion in the higher phospholipid/triglyceride-ratio (0.06 resp. 0.12). Lipid infusion was commenced at 0.5 g triglyceride/kg/24 hours and increased steadily to 2 g triglyceride/kg/24 hours. The aim of the study was to compare the effects of the two intravenously administered lipid emulsions on serum clearance. The serum concentrations of triglyceride and cholesterol did not change significantly during the infusion with 20% Lipovenos. Significant increases in the triglyceride and cholesterol content were observed only in the serum of the patients who were given the 10% Lipovenos. The reduced lipid serum clearance is attributable to the higher content of phospholipids in the 10% lipid emulsion. With regard to the risk of high cholesterol concentrations and an abnormal LPX serum accumulation, administration of 20% lipid emulsion is preferable to 10% lipid emulsion, also during the neonatal period. PMID- 1740901 TI - [Reference values for the concentration of free triiodothyronine (FT3), triiodothyronine (TT3), free thyroxine (FT4), thyroxine (TT4), thyrotropin (TSH) and thyroxine-binding globulin (TBG) in umbilical cord blood. Method: luminescence-enhanced enzyme immunoassay]. AB - Physiological concentrations of FT3, TT3, FT4, TT4, TSH and TBG were determined using the luminescence enhanced enzyme immunoassay method in cord blood serum (n = 100). The results are presented in Table 1. PMID- 1740902 TI - Spondylo-costal dysostosis in two siblings. AB - Two new cases of Spondylo-Costal Dysostosis (SCD) are reported in two siblings with strikingly similar skeletal abnormalities. Parental consanguinity documents in this family an autosomal recessive inheritance of trait. Clinical variability of SCD is discussed on the basis of clinical and radiological features. Its genetic heterogeneity is pointed out even considering the occurrence of cases with autosomal dominant as well as recessive inheritance. PMID- 1740903 TI - [Ultrasonically-guided percutaneous puncture and drainage of a splenic abscess caused by Salmonella heidelberg in a child]. AB - In a boy aged 9 years and 11 months pain developed in the left upper abdomen following Salmonella enteritis infection. Purulent splenitis was diagnosed by sonography. Ultrasonically guided percutaneous puncture and drainage, and appropriate chemotherapy led to a marked improvement in the clinical picture and finally to complication-free remission. In a review of the literature the problems associated with purulent splenitis and the possibility of treating it by percutaneous puncture are pointed out. Purulent splenitis should be considered in all patients with temperatures and unexplained abdominal pain. PMID- 1740904 TI - [Anamnestic factors in at-risk SID children with peculiar breathing pattern]. AB - 436 out of about 9000 infants who were born between April 1987 and November 1990 in Jena were selected by means of a risk score for a polygraphy monitoring. This score contains anamnestic factors of the mother and the infant which are characteristic of an enhanced risk for the sudden infant death syndrome (SIDS). We performed a day-time polysomnography (ECG, heart rate, respiration, EEG, EOG, EMG) with a sleep duration of at least one hour. 23 of the infants investigated demonstrated abnormal breathing patterns (increased mean apnea duration, apneas longer than 15 s, apneas with bradycardia) and were treated with aminophylline to prevent a possible SIDS event. Now we investigated the statistical relation between 26 anamnestic factors of our risk score and the need for treatment. In univariate statistical comparisons treated infants differed from untreated infants concerning the occurrence of intraventricular haemorrhages (IVH), the gestational age (GA) (preterm of fullterm) and the occurrence of hyperbilirubinemia (HB) in their anamnesis. In a multivariate analysis with all 26 factors the birth weight was the third important factor beside IVH and GA, but only factor IVH was statistically significant. A cluster analysis of the variables with respect to the separation of the two groups of infants indicates that the variables IVH, GA and HB strongly correlate. In the light of these results we can underline that abnormal breathing patterns can be expected especially in infants with IVH, short GA and low birth weight. PMID- 1740905 TI - [Agnes Karll Institute for Nursing Research]. PMID- 1740906 TI - [The future of the formation of teachers for the health professions]. PMID- 1740907 TI - [Talk among patients]. PMID- 1740908 TI - [Dying--a time of life]. PMID- 1740909 TI - [Occupational diseases]. PMID- 1740910 TI - [Honey on the wound]. PMID- 1740911 TI - [When costs point steeply upward]. PMID- 1740912 TI - [Method of documentation in decubitus. Decubitus protocol allows for more effective treatment]. PMID- 1740913 TI - [What to do about dependency, caused by the hospital]. PMID- 1740915 TI - [Only a favorable learning climate can promote education. Interview by Fred Arm]. PMID- 1740914 TI - [How seriously do you take hygiene regulations?]. PMID- 1740916 TI - [Good bye, thank you, no more room]. PMID- 1740917 TI - [The health care system in upheaval. Let us seize the opportunity]. PMID- 1740918 TI - [Explanations by the Swiss Nursing Association of the public initiative for financially acceptable health insurance (poll of February 16, 1992): no contribution to the solution of the problem]. PMID- 1740919 TI - [Many family members push us into an unfortunate role]. PMID- 1740920 TI - [Nurses between medicine and society. History, to help us understand]. PMID- 1740921 TI - [Intensive care in the Valais. Ecology of past-diploma nursing education]. PMID- 1740923 TI - [Home care aide: Geneva should speak out]. PMID- 1740922 TI - [Home care in the canton of Neuchatel. A new agreement on fees]. PMID- 1740924 TI - [From exhaustion to dynamic research]. PMID- 1740925 TI - [Nursing and computers: Melbourne congress 1991. Nurses are more and more involved]. PMID- 1740926 TI - [Running an interdisciplinary team in community health care: a must for those responsible for the team]. PMID- 1740927 TI - [Vote on 16 February 1992 on the popular initiative for a financially affordable health insurance]. PMID- 1740928 TI - [Clinical cancer research and the nurse's role. Cancer research requires competence]. PMID- 1740929 TI - Improved sterile technique diminishes the incidence of positive line cultures in cardiovascular patients. AB - In order to determine the incidence of positive line cultures, especially as affected by differing protocols for line insertion, cultures were obtained from lines in residence for up to 4 days from cardiac patients (who received Cefuroxime) and vascular patients (who received Cefazolin) as prophylaxis perioperatively. Positive cultures were obtained from 95 (19%) of 496 lines in cardiac patients and 83 (31%) of 261 lines in vascular patients. There was a linear relationship between duration of line residence and the incidence of positive line cultures, increasing from 14% on Day 1 to 33% on Day 4. The use of full sterile technique at the time of insertion halved the incidence of subsequent positive line cultures. Four of the 403 (1%) patients each had a single episode of postoperative line sepsis. Another four patients developed wound infections with the same organisms as cultured from their lines. One patient has had a vascular graft infection with the same organism cultured as was isolated from a Swan-Ganz line 1 year previously. These data suggest that monitoring lines should be inserted using full sterile technique and removed as soon as the patient is hemodynamically stable. PMID- 1740930 TI - Post-herniorrhaphy urinary retention: a randomized prospective study. AB - Urinary retention is a known complication of inguinal herniorrhaphy. Bladder distension due to vigorous fluid administration is believed to contribute to this problem. Our hypothesis is that fluid restriction will lower the incidence of urinary retention, post-herniorrhaphy. From January 1989 through March 1991, 113 male patients entered the study. Sixty patients (Group I) received unlimited iv fluids (1294 +/- 58 ml) and 9 patients (15%) developed urinary retention. Fifty three patients (Group II) received 500 ml or less by protocol (485 +/- 2 ml) and 5 of these patients developed retention (9%). Thus, fluid restriction lowered the incidence of urinary retention post-herniorrhaphy but the difference did not reach statistical significance. In addition age over 60 years approached significance as a risk factor for postoperative urinary retention. PMID- 1740931 TI - Management of local recurrence in well-differentiated thyroid carcinoma. AB - Local recurrence of well-differentiated thyroid carcinoma has a reported mortality approaching 50%. The University of Kentucky experience was reviewed to determine whether aggressive surveillance and treatment with reoperation and/or I 131 ablation increased survival following recurrence. Records of 66 consecutive patients with well-differentiated thyroid carcinoma treated at the University of Kentucky Medical Center (1980-1989) were reviewed. Forty-nine cases of papillary carcinoma and 17 cases of follicular carcinoma were studied; median follow-up was 68 months. At presentation, patients with follicular carcinoma were older (48 versus 35 years; P less than 0.05) and more frequently had metastatic disease (17% versus 2%, P less than 0.05). Fifty-eight (88%) patients were alive and disease-free at last follow-up. Fifteen patients (24%) had developed recurrent disease; median time to recurrence was 24 months. Multivariate regression examined the variables of age, sex, histology, tumor size, cervical adenopathy, capsular and vascular invasion, multicentricity, and surgical procedure. While distant metastases affected actuarial survival, no factor independently predicted local recurrence. In six patients with local recurrence, nonpalpable disease was detected by I-131 scan. All were treated with ablation and remain disease-free (mean follow-up 42 months). Eight patients with local recurrence presented with palpable lesions; seven underwent surgery. While two patients developed repeated local recurrences, the other five remain disease-free (mean follow-up 52 months). Early detection and aggressive treatment of local recurrence improve survival in patients with well-differentiated thyroid carcinoma. To facilitate use of I-131, we advise total thyroidectomy for patients with well-differentiated thyroid carcinoma. PMID- 1740932 TI - Serosal patching impairs intestinal adaptation following enterectomy. AB - Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740933 TI - The effect of fibrin glue on intraperitoneal contamination in rats treated with systemic antibiotics. AB - Intraperitoneal fibrin sealant lowers septic mortality in a rat model of peritoneal contamination (2 x 10(6) organism inoculum) at the cost of increased late intraabdominal abscesses. This study utilized parenteral antimicrobials to determine if the protective effect of intraperitoneal fibrin could be achieved without increasing the late abscess formation rate. One hundred and fifty-five rats were divided into four groups. Gelatin capsules containing various dilutions of feces (10(10) CFU/ml) and barium sulfate were placed into the abdomen in all groups. Group I controls had no antibiotics or fibrin. In group II, the capsule was surrounded by a solution of cryoprecipitate, thrombin, and calcium (fibrin "glue"). Groups III (no fibrin, antibiotics) and IV (fibrin, antibiotics) received a broad-spectrum cephalosporin intramuscularly postoperatively and then daily. Surviving rats were sacrificed on the tenth postoperative day. At a moderate volume of fecal inoculum (0.3 ml), fibrin reduced mortality from 100% in the control group to 0% in treated animals (P less than 0.001) that did not receive antibiotics. Abscesses formed in 10% of the surviving fibrin-treated rats which were implanted with 0.1 ml of inoculum. In the 0.2 and 0.3 ml inoculum groups substantially more abscesses occurred (75 and 70%, respectively). The protective effect of fibrin was not manifested in the antibiotic-treated rats since no deaths occurred in either group. At higher and lower inoculum doses, no significant differences between fibrin and control groups were observed in mortality or abscess formation, whether or not antibiotics were given.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740934 TI - The critical relationship of antibiotic dose and bacterial contamination in experimental infection. AB - Even though the usefulness of prophylactic antimicrobial administration for potentially contaminated operations is widely accepted, infection continues to occur in a finite number of cases. This study examined whether potential infection due to an increasing bacterial inoculum can be prevented or controlled by increasing antimicrobial doses. In an initial set of experiments, Sprague Dawley rats were given various doses of cefazolin (15, 30, 60, 120 mg/kg) intraperitoneally, then serum and tissue levels were quantified. Serum and tissue drug concentrations correlated with the dose given. In another set of experiments, rats were given doses of either 0, 30 (standard dose), 60, or 120 mg/kg of cefazolin 30 min prior to subcutaneous inoculation of various doses of Staphylococcus aureus. After 6 days, inoculum sites were examined for abscess formation and size. At low levels of contamination, increasing in antibiotic dose to 30, 60, and 120 mg/kg, abscess formation was eliminated at 50, 80, and 92% of inoculum sites, respectively. At moderate levels of contamination, abscesses formed at all inoculum sites, but abscess size was significantly smaller as the dose increased. When a high inoculum of S. aureus was given, large doses of antibiotics provided no additional benefit. These data suggest that the risk of infection in this model of experimental infection is significantly related to the size of the bacterial inoculum. Increasing the dose of an effective antimicrobial increases drug concentration at the site of contamination and reduces the risk of infection. Administration of higher doses of prophylactic antimicrobials may be more effective when larger amounts of bacterial contamination are anticipated. PMID- 1740935 TI - Protein and energy tolerance by stressed geriatric patients. AB - Nutritional support of stressed geriatric patients remains empiric and has classically been limited by tolerance. Although the hypermetabolic response is known to increase protein and calorie demands, tolerance to increased loads of delivered nutrients in older patients has been questioned. We compared tolerance to nutrient delivery and nitrogen metabolism in 38 stressed surgical patients over age 65 to 38 Injury Severity Score or disease matched younger controls. Twenty-seven of the 31 geriatric patients (87%) who maintained normal renal function (serum creatinine less than 2.0 mg/dl) became azotemic (BUN greater than 30) while receiving 1.5 to 2.0 g of protein per kilogram of ideal body weight compared to only 21% of controls. This phenomenon led to inaccuracies in 17% of geriatric nitrogen balance studies because of unaccounted for serum accumulation of urea nitrogen (compared to only 6% in the control group). When calculated protein requirements were administered to the geriatric group, the mean nitrogen balance was -1.6. Resting energy expenditure as measured by indirect calorimetry demonstrated a strong correlation between actual calorie expenditures and calculated needs based on the Harris-Benedict basal energy expenditure (BEE) multiplied by an activity factor of 1.2 and a stress factor of 1.75 for trauma (r = 0.86, P less than 0.05) or 1.5 for general surgery patients (r = 0.72, P less than 0.05). In summary, energy requirements by stressed geriatric patients can be closely defined by calculation of the Harris-Benedict BEE in conjunction with appropriate activity and stress factors. However, attempts to deliver traditional levels of protein lead to azotemia and are frequently unsuccessful in achieving positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740936 TI - Use of stress thallium imaging to stratify cardiac risk in patients undergoing vascular surgery. AB - Reduction of the cardiac morbidity associated with major vascular procedures requires identification of high risk patients prior to operation. This retrospective study reviews the records of 126 consecutive patients who underwent 141 major vascular procedures to determine the accuracy of preoperative clinical, laboratory (ECG), and cardiac function testing (stress thallium-201 scintigraphy, left ventricular ejection fraction scan) in predicting perioperative cardiac complications. An abnormality on oral dipyridamole or treadmill thallium imaging was demonstrated prior to 71 (61%) of 116 procedures and included 20 fixed and 51 reperfusion (reversible) defects. No patient died within 30 days of operation, but 11 minor (ventricular arrhythmia) and 15 major (myocardial infarction, ischemic congestive heart failure) cardiac complications occurred. A reperfusion defect on stress thallium imaging accurately (94% sensitivity, 56% specificity, 98% negative predictive value) identified high-risk patients while accepted clinical rating systems (Goldman, Cooperman, Eagle) and preoperative level of left ventricular ejection fraction were less predictive of adverse cardiac events. Patients without myocardium at risk by coronary angiography, but a reperfusion defect on stress thallium imaging were found to be at high risk for a cardiac complication. The study data support the use of stress thallium imaging to stratify cardiac risk prior to major arterial surgery. PMID- 1740937 TI - Neutrophil (PMN) phagocytosis and chemotaxis after reperfusion injury. AB - Neutrophils (PMN) have been implicated as mediators of the reperfusion injury which occurs in skeletal muscle after ischemia. This study was performed to measure PMN phagocytosis and chemotaxis after 3 hr of ischemia followed by 1 hr of reperfusion in a model where a significant reperfusion injury occurred. Baseline blood samples were drawn from an ear artery from New Zealand white rabbits for PMN and serum. The right iliac and femoral arteries were clamped for 3 hr which resulted in a severe clinical reperfusion injury. Just prior to clamp release, blood was harvested from the right iliac vein. After 1 hr of reperfusion, blood was again harvested from the right iliac vein. Phagocytosis was measured by the percentage ingestion of zymosan beads by the PMN. The zymosan beads had been opsonized with baseline (b), ischemia (i), or reperfusion (r) serum. Results for phagocytosis revealed no difference for (b) PMN when opsonized by (b), (i), or (r) serum. A significant increase was seen in (i) PMN phagocytosis when (i) or (r) serum was present. Also, a significant increase in (r) PMN phagocytosis was seen when (i) serum was present (ANOVA: F = 14.47; P = 0.0002). Chemotaxis was evaluated by the number of PMN migrating across a filter. Serum obtained from (b), (i), and (r) blood samples served as the chemoattractants. Significant increases in chemotaxis were observed for (b), (i), and (r) PMN when (i) serum was used as the chemoattractant (ANOVA: F = 7.11; P = 0.0025). We conclude: (1) Rabbit PMN harvested after ischemia and reperfusion demonstrated increased phagocytosis when (i) serum was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740938 TI - Hepatic function after porto-systemic shunt. AB - Advanced hepatic injury can be identified by the appearance of jaundice, coagulopathy, or encephalopathy but these conditions are late, irreversible findings and represent the end stage of a long insidious process. Currently available methods for assessing "liver function" (SGOT, SGPT, GGT, LDH, etc.) do not actually measure liver function. In this study we prospectively evaluated "true" liver function in patients undergoing porto-systemic shunt. Effective hepatic blood flow [low dose galactose clearance (EHBF)], hepatocyte transport (theophylline levels at 24 hr), and hepatic conjugation ability [acetaminophen metabolism to its glucuronide and sulfate conjugates ( (S + G)/A) and acetaminophen remaining at 24 hr (A24)] were measured in normal males (NL) and in patients pre- and post-8-mm H-graft portacaval shunt (PCS). All data are means +/ SEM, analyzed by Student's t test, and significance was accepted if P less than 0.05. There were no significant differences in EHBF even after PCS. Hepatocyte transport was decreased in pre-op (1.43 +/- 0.16 vs 0.74 +/- 0.08) and post-op (1.79 +/- 0.34) PCS patients. Hepatic conjugating ability was also decreased in pre-op PCS patients [A24 was increased (0.24 +/- 0.11 vs 0.01 +/- 0.01) while the ratio of conjugation products to acetaminophen remained the same]. The ability of the liver to conjugate substrate was severely compromised postoperatively [A24 - 1.27 +/- 0.67, (S + G)/A - 1.19 +/- 0.34]. We believe that changes in liver function can be accurately measured using these noninvasive methods, and in using these methods we have identified altered hepatocyte transport and conjugating ability in patients undergoing porto-systemic shunt surgery. PMID- 1740939 TI - The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury. AB - Burn injury induces immune suppression and increases susceptibility to infection. Hypoalbuminemia is an early and consistent finding following thermal injury and is independently associated with gastrointestinal dysfunction and increased rates of infectious morbidity. This study assessed the effects of albumin resuscitation on burn-induced immunosuppression, bacterial translocation, and absorption of gut endotoxin. Male Sprague-Dawley rats, presensitized to keyhole limpet hemocyanin (KLH), underwent a 20% dorsal scald burn injury, followed by laparotomy and IVC catheterization for fluid resuscitation. Animals were randomized to one of three resuscitative regimens: Ringer's lactate 3 ml/kg/% burn, Ringer's lactate 9 ml/kg/% burn, or 5% human albumin 3 ml/kg/% burn. Delayed hypersensitivity (DTH) responses to KLH were depressed 24 hr following injury (preburn 8.9 +/- 0.2 mm, post-burn 3.1 +/- 0.3 mm, P less than 0.001) and were significantly lower in animals in whom gram-negative bacterial translocation had occurred (2.3 +/- 0.4 vs 3.6 +/- 0.2 mm, P less than 0.005). Serum albumin levels were lower and rates of gram-negative bacterial translocation higher for those animals receiving low volume crystalloid resuscitation; animals resuscitated with albumin or high volume crystalloid experienced similar degrees of postinjury hypoalbuminemia and bacterial translocation. Uptake of radiolabeled endotoxin was maximal in animals resuscitated with albumin. Bacterial translocation is believed to be responsible for a significant number of late nosocomial infections following trauma. These data suggest that the adequacy of early resuscitation rather than the type of resuscitative solution is the more important factor in minimizing translocation. PMID- 1740940 TI - The effect of fuel source on amino acid metabolism in critically ill patients. AB - The ideal energy substrate for critically ill patients receiving total parenteral nutrition (TPN) remains controversial. While glucose has been proved to have nitrogen sparing properties in postoperative patients, critically ill patients tolerate glucose loads poorly and fat appears to be an obligatory fuel in sepsis. Furthermore, it is not yet certain whether the changes in whole body protein metabolism induced by critical illness are influenced by the nature of the TPN provided. This study was conducted on patients admitted to a surgical intensive care unit (SICU) who fulfilled the criteria of requiring TPN and mechanical ventilation for at least four days. Patients were randomized to receive either glucose (G) or equicaloric proportions of glucose and lipid (GF) as an intravenous energy source. TPN was commenced early, within 24-48 hr of trauma or surgery and admission to the ICU. Nonprotein calorie intake was 125% of calculated basal energy expenditure. Nitrogen balance was calculated from 24-hr urinary urea excretion. Protein synthesis, turnover, and catabolism were measured on Day 4 of the study using an established radiolabeled C14-leucine technique. Degree of sepsis and illness were calculated using published scores. Fifty patients entered the trial but 32 were excluded by Day 4. Of the 18 patients completing an initial four day study, eight went on to complete a second study on the alternative regimen--a total of 26 studies (14 G, 12 GF). Net protein synthesis was achieved in 18 studies (12 G, 6 FG) and positive nitrogen balance by Day 4 in 22 studies. Four patients on the G regimen were withdrawn due to glucose intolerance while none of the patients on GF developed glucose intolerance or hyperlipidaemia. Both whole body protein synthesis and catabolism correlated significantly with degree of sepsis. The type of TPN fuel used, G and GF, did not appear to influence whole body protein dynamics, both regimens achieving greatly improved whole body protein kinetics. PMID- 1740941 TI - Augmentation of acute random pattern skin flap viability in the pig. AB - Three experiments were conducted to study the effect of ketanserin and LY53857, S2-serotonergic receptor antagonists, on skin blood flow and viability in acute random pattern skin flaps (4 x 10 cm) in the pig. In experiment 1, the dose response effect of intravenous ketanserin (0, 0.15, 0.25, 0.35, and 0.50 mg/kg) on skin flap capillary blood flow was studied 6 hr after skin flap surgery, using the radioactive microsphere (15 microns) technique and under pentobarbital anesthesia. Significant (P less than 0.05) increase in skin flap blood flow was seen at the dosages of 0.25 and 0.35 mg/kg compared with the saline-treated control. In experiment 2, the effect of five-day intramuscular ketanserin and LY53857 treatment (0.30 mg/kg/day; in divided doses) on skin flap viability was studied. The drug treatments were started two days preoperatively. It was observed that the length of skin flap viability in ketanserin (6.6 +/- 0.2 cm; n = 40 flaps) and LY53857 (6.8 +/- 0.3 cm; n = 40 flaps) treated flaps were significantly (P less than 0.05) higher than the saline-treated control (5.5 +/- 0.1 cm; n = 48 flaps). Ketanserin treatment started 30 min after flap surgery also significantly (P less than 0.05) increased the length of skin flap viability (6.1 +/- 0.1 cm) compared with the control. There was no significant difference in skin viability between ketanserin and LY53857 treated skin flaps. The preceding study on the effect of ketanserin treatment on random pattern skin flap viability was repeated in experiment 3. Again, it was observed that intramuscular ketanserin treatment significantly (P less than 0.05) increased the skin flap viability. It was concluded that ketanserin and LY53857 treatment resulted in significant augmentation of porcine acute random pattern skin flap viability. This is the first experimental evidence to indicate that S2-serotonergic receptors participate in the pathogenesis of skin flap ischemia. PMID- 1740942 TI - Impaired energy metabolism of lymphocytes in cirrhotics after hepatectomy. AB - To clarify the mechanism of high susceptibility to infection in cirrhotics, the changes in adenylate energy charge and MTT assay in peripheral blood lymphocytes were studied in cirrhotic and noncirrhotic patients in the early postoperative period after hepatectomy. The adenylate energy charge measured by radioactive labeling of the lymphocyte adenine nucleotide pool showed no significant difference preoperatively between cirrhotics and noncirrhotics, but a significant difference was observed in the pre- and postoperative distribution of adenine nucleotide metabolites (P less than 0.01). In the cirrhotic group, the adenylate energy charge of lymphocytes decreased significantly to 0.807 +/- 0.011 on the third postoperative day compared with preoperative value (0.891 +/- 0.006, P less than 0.01) and was restored to the normal range on the fifth and tenth postoperative days (0.886 +/- 0.006, 0.899 +/- 0.014), while no significant decrease was observed in the noncirrhotic group. MTT assay revealed that lymphocyte cell function decreased significantly in cirrhotics after hepatectomy. These results indicate that, in cirrhotic patients, the energy metabolism of lymphocytes is already impaired to some extent preoperatively, and that it undergoes further deterioration when surgical stress is applied. It is suggested that the decreased energy metabolism in the lymphocyte may be responsible for the increased susceptibility to infection in postoperative cirrhotics. PMID- 1740943 TI - Quality assurance and morbidity and mortality conference. AB - Many surgeons assert that Morbidity and Mortality (M & M) conference in itself assures an effective quality assurance (QA) program. Recent emphasis on QA in other sectors has resulted in other processes for evaluating quality of care. The goals of QA programs are to identify adverse patient care events, relate these to specific physicians and use this information to improve patient care, and for credentialing and privileging physicians. Our aim was to determine the role of surgical M & M conference in a QA program which also includes occurrence screening, wound infection surveillance, and surgical case review. The weekly M & M conference is a discussion of identified complications and deaths submitted voluntarily by surgeons. During a 2-year period 5755 procedures were associated with 255 complications and 82 deaths. Only 74% of events identified by occurrence screening, 35% of cases identified by surgical case review, and 54% of wound infections had been submitted to M & M conference. Seventy-four percent of surgical residents and 33% of staff surgeons were present at M & M conference when their complications were discussed. Level of care (I, accepted practice; II, may have managed differently; and III, would have managed differently) was assessed for each complication at M & M conference and by peer review of the medical record for occurrence screening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1740944 TI - [The American FDA recommends suspension of the use of silicone breast implants]. PMID- 1740945 TI - [How to simplify complicated randomization]. PMID- 1740946 TI - [Flumazenil--a valuable diagnostic agent in coma but only with clear indications]. PMID- 1740947 TI - [Quality and safety are more important than price when buying radiologic equipment]. PMID- 1740948 TI - [Disposable insulin pen can relieve pressure on home care services]. PMID- 1740949 TI - [Autism and mental retardation. More attention should be paid to sibling relations when helping families with severely handicapped children in the future]. PMID- 1740950 TI - [Actinomycosis, an infection difficult to diagnose and requiring extremely prolonged antibiotic therapy]. PMID- 1740951 TI - [The man behind the syndrome. Nicholas A. Halasz--the man behind a rare abnormality. The scimitar syndrome--a condition with the scimitar formed shadow]. PMID- 1740952 TI - [Hydatid cyst of the spleen is an unusual diagnosis in Sweden]. PMID- 1740953 TI - [Kidney failure and severe gastrointestinal symptoms were diagnosed as amyloidosis]. PMID- 1740954 TI - [Repeated coagulation analyses were crucial in a case of hepatorenal syndrome]. PMID- 1740955 TI - [Flupenthixol poisoning. The patient drank a depot preparation intended for intramuscular injection]. PMID- 1740956 TI - [A patient inquiry on the quality assurance work at an oncologic clinic. Patients' communication needs are not sufficiently cared for at present]. PMID- 1740957 TI - [Is the patient feeling as well as expected? New measurement methods can answer questions on quality of life of patients with heart surgery]. PMID- 1740958 TI - [The committees on medical research ethics should change their practice. Focus on projects difficult to evaluate, justify decisions]. PMID- 1740959 TI - Effect of sodium ascorbate on the chemiluminescent response of murine peritoneal exudate cells. AB - Vitamin C is an effective antioxidant that neutralizes reactive oxygen radicals. The purpose of this study was to determine if sodium ascorbate would neutralize the reactive oxygen products generated during the respiratory burst of thioglycollate-elicited murine peritoneal exudate cells (PEC). In vitro and in vivo studies were done. Cells treated in vitro showed a significant, dose dependent reduction in chemiluminescence (CL) after activation with opsonized zymosan. Higher concentrations of sodium ascorbate (24.2 mM) produced a significantly greater reduction in CL than did lower concentrations (0.242 mM). This range of sodium ascorbate concentrations overlaps those found in normal leukocytes (1-4 mM). Sodium ascorbate at physiological plasma concentrations (0.09 mM) did not reduce CL. Cells incubated with 500 mM sodium ascorbate in vitro and then washed once prior to zymosan activation also showed a significant reduction in CL. In contrast, PEC harvested from mice treated in vivo with sodium ascorbate (one or five daily doses of 1.0 M sodium ascorbate, 0.01 ml/g body weight) did not show a reduction in CL. This concentration of sodium ascorbate represents a dose that is 2310 times greater than the Recommended Dietary Allowance (RDA). These studies show that physiological doses of sodium ascorbate can quench CL in vitro, but even large doses of sodium ascorbate administered in vivo do not affect the CL of harvested murine PEC. PMID- 1740960 TI - Insulin secretion and protein phosphorylation in PKC-depleted islets of Langerhans. AB - Protein kinase C (PKC)-dependent phosphorylation of endogenous substrates was measured in electrically permeabilised rat islets of Langerhans. The PKC activating phorbol ester, 4 beta-phorbol myristate acetate (PMA), caused a slow but prolonged increase in insulin secretion from permeabilised islets, which was accompanied by increased 32P incorporation into several islet proteins of apparent M.W. 30-50 kDa. Depletion of islet PKC by prolonged exposure to PMA abolished subsequent secretory and phosphorylating responses to the phorbol ester. However, PKC-depleted islets did not show diminished responses to glucose, suggesting that PKC-mediated phosphorylation of these proteins is not essential for nutrient-induced insulin secretion. PMID- 1740961 TI - Islet hormone pulse intervals are dependent upon sampling frequency. AB - Pulsatile insulin secretion has been reported from a variety of in vivo and in vitro systems. While it is agreed that insulin pulses exist, there is little agreement concerning the basal frequency or interpulse interval either within the same species in vivo, as both long and short term pulses have been reported, or between in vivo and in vitro preparations. We propose that the frequency of sampling may have profound effects upon the calculated pulse interval. Three systems were used to test this hypothesis: 1) artificial test data were designed to produce regular pulses with an exact 11 min period, 2) perfusate insulin concentration from isolated canine pancreata sampled at 1 min intervals and 3) peripheral blood insulin concentrations from human volunteers sampled every 2 and 5 min. Pulse parameters were determined at 1, 2, 5, 20, 15, 30 and 60 min sampling intervals for each data set by the use of the computer algorithms Pulsar and Cycle Detector. The results indicate that for insulin secretory pulses, sampling frequencies longer than 2 min may result in the production of spurious pulse trains with multiple longer term pulse periods. It is concluded that islet hormone secretory pulse period calculations are dependent upon the sampling frequency. PMID- 1740962 TI - Negative regulation by dexamethasone of the potentiation of neuromedin C-induced growth hormone and prolactin release by estradiol in anterior pituitary cell aggregates. AB - The bombesin-like peptide neuromedin C (NMC) stimulated the release of growth hormone (GH) and prolactin (PRL) from adult male rat anterior pituitary cell aggregates cultured in serum-free medium. This effect, particularly on GH release, was significantly increased when the cells were cultured in the presence of estradiol (E2). The GH response to NMC was not affected by 4 nM dexamethasone (Dex) but was enhanced in the presence of 80 nM Dex. However, the strong stimulatory action of E2 on the GH response to NMC was completely abolished by 4 nM Dex. In contrast, the PRL response to NMC was reduced by 4 nM Dex and this to a proportionally similar extent in the presence or absence of E2. The present data show that glucocorticoids can be both positive and negative regulators of the same response system. PMID- 1740963 TI - Involvement of the muscarinic receptors in the postsynaptic potentiation of neurogenic twitch contraction in the mouse vas deferens. AB - Muscarinic agonists and three selective antagonists were used in an attempt to characterize the muscarinic receptor subtypes which regulate the electrically evoked, neurogenic twitch contraction of the mouse vas deferens. The neurogenic contraction was concentration-dependently potentiated by both carbachol and oxotremorine, but not McN-A-343. These agonists also potentiated the contraction of unstimulated preparations elicited by exogenous ATP. However, potentiation of the neurogenic twitch contraction was strongly antagonized by pretreatment with 4 DAMP (IC50 = 1.38 nM for carbachol, and 4.79 nM for oxotremorine). The inhibitory effects of methoctramine and pirenzepine (PRZ) were about 100 times lower than those of 4-DAMP; the descending order of antagonistic potencies was: 4-DAMP much greater than methoctramine approximately equal to PRZ. These results suggest that muscarinic receptors are involved in the postsynaptic potentiation of the neurogenic twitch contraction in the mouse vas deferens. Classifications for the muscarinic receptor subtypes were discussed. PMID- 1740964 TI - Serum phospholipase A2 enzyme activity and immunoreactivity in a prospective analysis of patients with septic shock. AB - Massive elevations of serum phospholipase A2 activity have been documented in patients with septic shock. Serum PLA2 activity correlated to the degree and duration of circulatory collapse, while purified native PLA2 reproduced hypotension in experimental animals. In a prospective study of patients with septic shock, we have determined the relationship of PLA2 enzyme activity to PLA2 immunoreactivity using radiolabelled E. coli phospholipid substrate and an ELISA specific for group II human nonpancreatic PLA2. In all patients, there was a clear concordance of the two assays. Maximal PLA2 concentration was increased a mean of 554-fold over normal levels. We found no evidence to support the presence of activating or inhibitory proteins. These data confirm that the observed increase in serum PLA2 activity in septic shock is due to intravascular release of group II nonpancreatic PLA2. PMID- 1740965 TI - Effect of serotonergic agonists in the nucleus accumbens on d-amphetamine stimulated locomotion. AB - Serotonergic projections from the raphe nuclei are thought to modulate locomotor activity in the rat, and serotonin injection into the nucleus accumbens attenuates the hypermotility elicited by amphetamine. The purpose of the present study was to characterize the effects of various classes of serotonergic agonists administered into the nucleus accumbens on d-amphetamine-stimulated locomotor activity in order to determine which serotonin receptor subtypes are involved. Administration of the nonselective 5-HT agonist quipazine, the 5-HT-1 agonist mCPP, the 5-HT-1a agonist 8-OH-DPAT, the 5-HT-1b agonist CGS-12066B, and the 5HT 1c/2 agonist DOI did not inhibit d-amphetamine-stimulated locomotor activity. Pronounced lateral head weaving was noted after 8-OH-DPAT administration. The combination of the 5-HT-1a agonist 8-OH-DPAT and the 5-HT-1b agonist CGS-12066B, however, did inhibit d-amphetamine-stimulated locomotor activity. In contrast, the 5-HT-3 agonist 1-phenylbiguanide enhanced the locomotor effect of d amphetamine. This effect was partially reversed by the 5-HT-3 antagonist MDL 7222. These studies suggest that serotonin has complex and multiple effects on the regulation of locomotor activity within the nucleus accumbens. PMID- 1740966 TI - Subacute reserpine treatment reveals preferential coupling between the M3 muscarinic receptor subtype and phosphatidylinositol turnover. AB - Muscarinic receptors in the rat cerebral cortex, cardiac atria and vas deferens were identified, quantitated, and characterized relative to phosphatidylinositol (PI) turnover as the functional response to stimulation of specific receptor subtypes. Receptor densities as determined by 3H-QNB binding were ranked: cerebral cortex greater than vas deferens greater than heart. Using displacement of 3H-QNB binding by the selective M1 and M2 muscarinic receptor antagonists pirenzepine and 11[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido [2,3-b] [1,4] benzodiazepine-6-one (AF-DX 116) respectively, heterogeneous populations were found in the cerebral cortex and vas deferens. The M1 receptor subtype predominated in the former and the M2 predominated in the latter. An homogeneous M2 receptor population was present in the heart. Methacholine-stimulated accumulation of 3H inositol-1-phosphate was greater in the vas deferens than in the cerebral cortex, whereas PI turnover was not enhanced in cardiac atria. Reserpine treatment of rats (0.5 mg kg-1 day-1 for 7 days) increased muscarinic receptor density in the vas deferens coincident with a shift in the low affinity pKi for AF-DX 116 to a value comparable to high affinity binding, and abolished the enhanced PI hydrolysis. In the cerebral cortex, reserpine treatment shifted only the early portion of the methacholine dose-response curve to the right. These results are judged to be supportive of preferential coupling between the M3 muscarinic receptor subtype and PI turnover. PMID- 1740967 TI - Muscarinic antagonists attenuate dizocilpine-induced hypermotility in mice. AB - Pretreatment of mice with the muscarinic receptor antagonists scopolamine and atropine attenuated the hypermotility (but not the depression of rearing) induced by a low dose of dizocilpine maleate [(+)-MK-801; 0.1 mg/kg, i.p.], a non competitive NMDA antagonist. In contrast, the muscarinic blockers failed to affect hypermotility induced by equieffective doses of phencyclidine (1 mg/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). These results suggest differences between the mechanism of behavioral activation produced by dizocilpine and phencyclidine, and demonstrate the potential of muscarinic blockade for diminishing the behavioral toxicity of NMDA antagonists. PMID- 1740968 TI - Degradation of human pancreastatin-52 by human kidney extract. AB - We examined the in vitro degradation of human pancreastatin-52 (hPST-52) and a larger molecular form (approximate 15 kDa) of human PST by an enzyme extract from human kidney. The PST-degrading activity was determined from the amount of immunoreactive PST remaining after incubation of hPST-52 or the larger molecular form with the enzyme extract. Human PST-52 was degraded to smaller molecular forms within 30 min, but the larger molecule was not degraded within 90 min. Phosphoramidon, an inhibitor of endopeptidase, metal ion chelators (EDTA and 1, 10-phenanthroline) and Cu2+ prevented the degradation of hPST-52. These results indicated that the enzyme in the kidney extract degraded hPST-52 and smaller forms of the peptide, but had no effect on the 15 kDa form. PMID- 1740969 TI - Identification of somatogenic binding sites in liver microsomes from normal mice and transgenic mice expressing human growth hormone gene. AB - Somatogenic binding sites were detected and characterized in microsomal preparations from livers of normal mice and mice expressing metallothionein-I/hGH (mMT/hGH) hybrid gene, using 125I-labelled bovine or human GH, or a photoreactive derivative of hGH (125I-AP-hGH1). Specific binding of 125I-bGH was detected in liver microsomes from both normal and transgenic mice with an apparent Kd of 2 nM. 125I-hGH was partially displaced by bGH. 125I-AP-hGH1 was covalently bound to the microsomal preparations, and bGH prevented the formation of the 130 kDa species with no appreciable effect on 63 kDa and 70 kDa lactogenic complexes. PMID- 1740970 TI - Effects of prenatal administration of testosterone and cortisone on the reproductive system of the female rat. AB - Testosterone propionate, cortisone, or sesame oil vehicle were given to rats during the last week of pregnancy so that effects of the hormones on anogenital distance, breeding capacity and vaginal opening of the female progeny could be contrasted. Testosterone significantly increased anogenital distance and delayed vaginal opening of progeny. When females that had been exposed to testosterone in utero were tested for breeding capacity, a significantly smaller number mated than in the control group. Female rats that had been exposed to cortisone in utero exhibited premature vaginal opening but did not differ from controls in anogenital distance, and, unlike the testosterone-exposed rats, mated. Cortisone exposed rats carried litters to term and the litters did not differ from those of controls in numbers of pups or numbers of living pups at birth. The pups born to cortisone-exposed rats had greater birth weights and a higher survival rate to 20 days of age than pups of controls. Results indicate that testosterone administration to rats during pregnancy is far more detrimental to the development and subsequent function of the reproductive system of female progeny than cortisone and suggest that similar changes which occur in response to maternal stress or to administration of ACTH during pregnancy are more likely to result from increases in testosterone than from increases in glucocorticoid secretion. PMID- 1740971 TI - The in vitro dissociation kinetics of (R,R)-[125I]4IQNB is reflected in the in vivo washout of the radioligand from rat brain. AB - We have determined the kinetics of dissociation of (R)-3-Quinuclidinyl (R)-4 [125I]Iodobenzilate ((R,R)-[125I]4IQNB) from muscarinic acetylcholine receptor preparations from the cortex, hippocampus, caudate/putamen, thalamus, pons and colliculate bodies. The dissociation curves are well described by a biexponential function and are consistent with subtype selectivity favoring slow dissociation from the M1, M3, and M4 receptors with a 20-fold faster dissociation rate for the M2 receptor. Following intravenous injection, (R,R)-[125I]4IQNB binds to receptor in the rat brain in concentrations which reflect the receptor concentration present in a structure. We determined the extent of radioligand present at two times, 2 and 24 hrs, as an indication of the relative proportions of m-AChR which exhibits rapid vs. slow dissociation of (R,R)-[125I]4IQNB. A good correlation between in vitro and in vivo results suggests that the relative populations of receptor subtypes can be imaged using in vivo pharmacokinetics of (R,R) [125I]4IQNB. PMID- 1740972 TI - Thyroxine attenuates hippocampal neuronal damage caused by ischemia in the rat. AB - We investigated the effect of thyroxine against neuronal damage caused by ischemia in the rat. Neuronal damage was evaluated in the hippocampal CA1 subfield 7 days after a 10 min forebrain ischemia. Thyroxine was administered to animals divided in three groups: 15 min prior to ischemia (group 1), immediately after ischemia (group 2), and both before and after ischemia (group 3). The treatment of rats with a single dose of thyroxine given pre- or postischemia failed to prevent the loss of CA1 pyramidal cells. In contrast, repetitive administration of thyroxine before and after ischemia reduced the damage of the CA1 pyramidal cells. The mechanisms possibly underlying this neuroprotective effect are discussed. PMID- 1740973 TI - A sensitive fluorometric assay for reducing sugars. AB - A simple and rapid fluorometric assay for reducing sugars that is sensitive to the nanomolar range has been developed. The assay involves the derivatization of a given sugar with hydrazine at pH 3 to form a hydrazone, which is reacted with fluorescamine following adjustment of pH to first 9.4 and then 7.4. The amount of sugar in a sample is quantitated by measuring the fluorescence intensity at an excitation wavelength of 400 nm and an emission wavelength of 490 nm. The assay is precise and reproducible, as indicated by intra- and inter-run variations of at most 3% and 4%, respectively. In addition to reducing sugars, the assay can also be used to measure aliphatic and aromatic aldehydes, but not acetone. Compared with an existing fluorometric sugar assay, the assay reported here does not require chromatographic separation of the fluorescent derivative from unreacted fluorescamine. The assay can, however, be potentially adapted for postcolumn detection of aldehydes, reducing sugars, and hydrazones in HPLC. PMID- 1740975 TI - Embryo research: an Islamic response. PMID- 1740974 TI - Inhibitory effect of 4-methylpyrazole on antipyrine clearance in rats. AB - Pyrazole and 4-methylpyrazole (4-MP) are potent, effective inhibitors of alcohol dehydrogenase. Pyrazole and its derivatives also have been shown to affect the cytochrome P-450 dependent monooxygenase system. This study was performed to investigate the effect of 4-MP on the disposition kinetics of antipyrine (AP). Groups of male Fisher 344 rats were given an ip injection of 4-MP (100 mg/kg) or 4-MP HCl (equivalent to 4-MP 100 mg/kg) or an equivalent volume of saline. AP (20 mg/kg) was injected intravenously via the jugular vein catheter 30 minutes later. Blood samples were collected upto 24 hours and assayed by HPLC. 4-MP pretreatment significantly decreased AP clearance from 0.490 +/- 0.032 to 0.095 +/- 0.014 (4 MP HCl) and 0.076 +/- 0.008 (4-MP) L/hr.kg (p less than 0.01). The volume of distribution of AP decreased from 0.82 +/- 0.07 to 0.65 +/- 0.06 (4-MP HCl) and 0.56 +/- 0.04 (4-MP) L/kg (p less than 0.05). Mean residence time increased from 1.68 +/- 0.09 to 6.91 +/- 0.58 (4-MP HCl) and 7.39 +/- 0.56 (4-MP) hr (p less than 0.01). These results demonstrate a significant inhibitory effect of 4-MP on the cytochrome P-450 isozyme(s) which is responsible for AP metabolism in intact animals. PMID- 1740976 TI - Submersion cases: a retrospective study--1988-1990. AB - According to the studied material the majority of the bodies found submersed in water (in the area covered by this report) were predominantly those of Caucasian males between 20 and 40 years of age, probably sober and without drug consumption when they entered the water. The majority of the cases were recovered from the water in the late spring and early summer and many of them were in different stages of decomposition which made the diagnosis of drowning impossible. The diagnosis of the cause and manner of death in such cases requires a complex interpretation of all investigative evidence and a logical approach in each case in particular. PMID- 1740977 TI - Acute pancreatitis: a comparison of the severity of illness in cases first diagnosed before and after death, using a modified prognostic index. AB - The severity of disease in a series of patients in whom acute pancreatitis was diagnosed at autopsy was assessed by the retrospective application of a standard prognostic index modified for post-mortem use. The results were compared with cases dying of acute pancreatitis which was recognized during life and appropriately treated. No difference in disease severity could be identified between the two groups. This suggests that patients dying of acute pancreatitis unrecognized during life have a severe form of the disease and do not die because a mild attack is treated inappropriately. The condition appears to be unrecognized in such patients because it presents with atypical features. PMID- 1740978 TI - About death. PMID- 1740979 TI - Insurance, reinsurance and underwriting names' liability for asbestos-related diseases. PMID- 1740980 TI - The medico-legal organization of a mass disaster--the Air India crash 1985. PMID- 1740981 TI - Criminal liability for the unauthorized use of corpses for medical education and research. PMID- 1740982 TI - Suicidal strangulation. AB - Self-strangulation for committing suicide by the use of ligature is admittedly rare. A suicidal strangulation case from Haryana State, India is discussed in the light of scene of occurrence, investigations of the ligature and its knot. Initially the case was suspected by the police to be a murder, but proved to be of suicidal strangulation. PMID- 1740983 TI - An unusual case of comingled remains. AB - Two motor cyclists were involved in a head-on collision. One of the motor cyclists sustained a stab wound to the chest by a portion of long bone derived from the other motor cyclist. This case is reported because of its unusual nature. PMID- 1740984 TI - An unusual injury. AB - The case of a young man who died unexpectedly from myocarditis is presented. The body was partially embalmed before autopsy at the Victorian Institute of Forensic Pathology. Although the cause of death was not a problem to diagnose, this case highlights artefacts that embalming may cause and the difficulties it may create with interpretation of injury. This is of particular relevance to those forensic pathologists who only uncommonly see injuries which are due to embalming. PMID- 1740985 TI - Tuberous sclerosis presenting as a suspicious sudden death--a case report and review of sudden deaths in epilepsy. AB - A case of a suspicious sudden death in a 19-year-old Caucasian female epileptic is presented. The brain showed characteristic lesions of tuberous sclerosis. In most sudden deaths in idiopathic epilepsy no causative lesion is found in the brain. A review of the past five years' cases attributed to sudden deaths in epilepsy from our department is presented, with particular reference to findings which might be construed as suspicious, e.g., signs of asphyxia and bruising in neck muscles, and to findings which support the diagnosis, e.g. biting of the tongue, voiding of urine, low levels of medication. PMID- 1740986 TI - A case of homicidal choking mistaken for suicide. AB - This report presents an autopsy case of the homicidal choking of an adult, who died as a result of tissue paper being thrust into his mouth. An in-patient (a 29 year-old Japanese man) at a mental hospital was choked to death by another male in-patient, his roommate, who thrust a large amount of tissue paper into his mouth after rendering him slightly unconscious by cervical compression. At the time of discovery, this mental patient was believed to have committed suicide by inserting tissue paper into his own mouth. Autopsy findings and re-investigation of the case revealed that the subject had been murdered. This is a very rare case of choking used as a method of homicide. PMID- 1740987 TI - An unusual case of accidental smothering. AB - A rare accidental death case is presented in which four pieces of packing tape adhered tightly over the nose and mouth. The notes for his experimental report, left in his room, suggested that the accident happened during his trial to prove his theory on respiration to improve physical exercise. PMID- 1740988 TI - Sub-lethal poisoning by self-injection with ricin. AB - Ricin, one of the most potent toxins known, has a lethal dose range of 1-10 mg per kilogram (Crompton and Gall, 1980) when injected. There is no effective treatment. We report a case of sub-lethal poisoning by self-injection. PMID- 1740989 TI - Dr Hunter and the hunted. PMID- 1740990 TI - Sleepwalking and indecent exposure. PMID- 1740991 TI - The certification and disposal of the dead in major disasters. AB - When a major disaster occurs in which there are a large number of fatalities, many tasks have to be undertaken in a very short time and under great pressure. By considering in advance the potential difficulties which may be encountered it is possible to plan ways of overcoming, or at least minimizing, some of these problems. In this paper we have ventilated some of the problems concerning the certification and disposal of the victims of a major disaster, as seen from the pathologist's point of view. PMID- 1740992 TI - Case in point: qualifications for job promotion. PMID- 1740994 TI - Women's health: a call for nursing action. PMID- 1740993 TI - Nursing needs in Mississippi: supply and demand. PMID- 1740995 TI - A comparison of infection rates in a newborn intensive care unit before and after adoption of open visitation. PMID- 1740996 TI - Frequency of hand washing by registered nurses caring for infants on radiant warmers and in incubators. PMID- 1740998 TI - Demonstration day: a unique way to learn. PMID- 1740997 TI - Factors that influence the use of universal precautions by neonatal nurses. PMID- 1740999 TI - Basic proficiency in medication administration. PMID- 1741000 TI - Pneumothorax in the newborn. PMID- 1741001 TI - U.S. maternal and child health services. PMID- 1741002 TI - Clinical trials. PMID- 1741003 TI - Education in the NICU. Special teaching needs of teen parents. PMID- 1741004 TI - Chloral hydrate. PMID- 1741005 TI - Beyond survival: strategies for establishing a follow-up program for infants treated with extracorporeal membrane oxygenation. PMID- 1741006 TI - HIV-risk behaviors of sterilized and nonsterilized women in drug-treatment programs--Philadelphia, 1989-1991. AB - From June 1981 through December 1991, 34% of all reported cases of acquired immunodeficiency syndrome (AIDS) among women in the United States were attributed to heterosexual transmission, and that proportion has been increasing steadily (1). Factors associated with an increased risk for heterosexual transmission include unprotected sexual intercourse (2), multiple sex partners, and the presence of other sexually transmitted diseases (STDs) (1). Women who have been surgically sterilized and who are sexually active and/or use injecting drugs may need the same prevention services for human immunodeficiency virus (HIV) and other STDs as similar nonsterilized women; however, the specific needs of sterilized women have not been well characterized. This report compares findings from surveys of surgically sterilized and nonsterilized women in drug-treatment programs in Philadelphia on their drug use and HIV/STD-risk behaviors and assesses changes in risk behaviors among these women after a 9-month period during which family-planning counseling and/or gynecologic services were offered. PMID- 1741007 TI - Medicare influenza vaccine demonstration--selected states, 1988-1992. AB - Influenza and its complications remain a major cause of premature death and debilitating illness in the United States, particularly among older persons and those with chronic medical conditions. However, only 30% of persons greater than or equal to 65 years of age responding to the 1989 National Health Interview Survey reported having received influenza vaccine during the previous year (CDC, unpublished data, 1991). In 1988, the Health Care Financing Administration (HCFA) and CDC began a congressionally mandated 4-year demonstration project to evaluate the cost-effectiveness of providing influenza vaccine under Medicare. This report reviews preliminary results of the Medicare Influenza Vaccine Demonstration during 1988-1992. PMID- 1741008 TI - Hepatitis A among homosexual men--United States, Canada, and Australia. AB - Although male homosexual activity has been reported as a risk factor for hepatitis A, the frequency with which homosexual activity was reported by persons with hepatitis A was less than 10% during 1982-1989 (CDC unpublished data, 1990). However, in June of 1991, CDC received reports from several cities in the United States, Canada, and Australia of an increase in hepatitis A among homosexual men during the first 6 months of 1991. This report summarizes data from each of these cities. PMID- 1741009 TI - Pertussis vaccination: acellular pertussis vaccine for reinforcing and booster use--supplementary ACIP statement. Recommendations of the Immunization Practices Advisory Committee (ACIP). AB - This supplementary statement provides information on and recommendations for the use of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP). One such vaccine was recently licensed, ACEL-IMMUNE.* This vaccine is licensed for use only as the fourth and fifth doses of diphtheria, tetanus, and pertussis vaccination; it is not licensed for the initial three-dose series in infants and children, regardless of age. At least one other DTaP product is anticipated to be licensed in the future for use as the fourth and fifth doses. The current Immunization Practices Advisory Committee (ACIP) statement on diphtheria, tetanus, and pertussis issued August 8, 1991, gives general recommendations on pertussis prevention, including the use of whole-cell pertussis vaccines for primary and booster vaccination (1). PMID- 1741010 TI - Effects of hypoxia and acute osmotic stress on intermediary metabolism in Leishmania promastigotes. AB - This study further explores the effects of hypoxia and acute osmotic stress on intermediary metabolism of Leishmania major and Leishmania donovani. Late log phase promastigotes were washed and incubated with glucose as the sole exogenous carbon source, and rates of glucose consumption and product formation were measured as a function of osmotic strength (610, 305, and 167 mOsm kg-1) and pO2 (95, 10, and 0% O2) in the presence of 5% CO2. Very mild hypoxia dramatically altered flux through the pathways of intermediary metabolism and increased the rates of production of the major metabolites, thus confirming the presence of a low-affinity O2 sensor which was active under all osmolalities tested. The data also require that as pO2 is lowered towards anoxia an endogenous carbohydrate source is mobilized. Under aerobic conditions, acute hypo-osmotic stress had little effect on product formation, whereas acute hyperosmotic stress altered metabolism in a manner similar to mild hypoxia, with the exception of decreasing the rates of acetate and succinate production. It was also shown in L. donovani promastigotes that the effects of anoxia and hyperosmolality were not additive. Thus, separate sensors with partially overlapping actions are involved in the metabolic responses to hypoxia and hyperosmolality. There was no apparent species specificity for the responses to pO2 and osmotic stress. Uncoupling with carbonyl cyanide p-trifluoromethoxyphenylhydrazone caused changes in metabolite flux patterns which differed from the changes caused by either hypoxia or acute osmotic stress, while rotenone and calcium ionophore A23187 had no significant effects. The identity of the sensors responsive to pO2 and osmolality, and the mechanisms by which they regulate flux through the pathways of intermediary metabolism, require further study. PMID- 1741011 TI - Ferritins of Schistosoma mansoni: sequence comparison and expression in female and male worms. AB - Recombinant clones of Schistosoma mansoni cDNA libraries containing the complete coding regions of 2 different ferritin subunits have been isolated and sequenced. This allows for the first time a comparison of ferritin sequences from an invertebrate with those of vertebrates. The deduced amino acid sequences of both Schistosoma ferritin subunit clones show significant homology to vertebrate ferritin H chains. Similarity exceeds 50% identity and includes the recently identified ferroxidase center which is present only in H chains. However, non conservative substitutions of amino acid residues lining the 3-fold symmetry channel were found, and a gap of 3 successive amino acids unique to the 2 Schistosoma ferritin sequences was identified. Remarkably, for each of the 2 genes, we found a conspicuous difference in the amount of ferritin transcripts between females and males: one of the genes is preferentially expressed in females, the other in males. PMID- 1741012 TI - Comparison of the body wall myosin heavy chain sequences from Onchocerca volvulus and Brugia malayi. AB - The complete coding sequence of Onchocerca volvulus myosin heavy chain has been determined from a series of overlapping cDNAs. The protein sequences from the 2 filarids, one responsible for subcutaneous filariasis, the other for lymphatic filariasis, show 92% identity, and are 1957 amino acids long. Each protein sequence is also equally related, with 75% identity, to MHC-B, the protein encoded by the unc-54 gene of the free-living nematode C.elegans. Such analysis is useful in phylogenetic studies among nematodes, as well as in structure function relationships among myosin isolates. PMID- 1741013 TI - Characterization of a myosin heavy chain gene from Brugia malayi. AB - We have previously shown that an antigen recognized by antibodies in sera of several microfilaremic individuals from a Wuchereria bancrofti endemic area bears strong homology to an invertebrate muscle protein. We have cloned and sequenced the entire gene containing this antigen encoding fragment and present data that confirms that the antigen is myosin heavy chain (MHC). This gene, which we have named Bmmyo-1 extends over 11 kb and has the potential to encode a protein of 1957 amino acids. The coding sequence is interrupted by 14 introns, most of which are larger than those in the myosin gene of the free-living nematode, Caenorhabditis elegans. The protein encoded by this gene bears greatest homology (75.1% identity) to the C. elegans myosin isoform MHC-B, encoded by the unc-54 gene. MHC-B is the major body wall myosin in C. elegans. PMID- 1741014 TI - Cysteine is an essential growth factor for Trypanosoma brucei bloodstream forms. AB - A modified cystine-free minimum essential medium has been used to address the question whether cysteine is an essential growth factor for bloodstream form trypanosomes or if its reducing power is sufficient to support parasite growth in axenic culture. Bloodstream-form trypanosomes, taken either from freshly isolated infected mouse blood or from logarithmically growing axenic cultures were transferred to a medium containing 20% dialysed foetal calf serum, 10 microM bathocuproine sulphonate and 250 microM cysteine. Growth curves of these cultures have been compared to those obtained in identical cultures containing no cysteine but cystine and reducing agents (beta-mercaptoethanol, monothioglycerol), or reducing agents alone. The results clearly show that cell growth was only obtained if cysteine was either directly added to the medium or was reduced from cystine by the action of reducing agents. However, neither reducing agents alone, nor D-cysteine, supported cell growth. Since cystine is not taken up by bloodstream form trypanosomes, and methionine is a regular constituent of the medium, we conclude from our results that cysteine is an essential growth factor for Trypanosoma brucei. PMID- 1741015 TI - Identification of a novel Brugia pahangi beta-tubulin gene (beta 2) and a 22 nucleotide spliced leader sequence on beta 1-tubulin mRNA. AB - We have examined the expression of beta-tubulin genes in the parasitic nematode, Brugia pahangi. A genomic library was constructed and screened by hybridization with a Haemonchus contortus beta-tubulin cDNA fragment which recognizes several B. pahangi beta-tubulin sequences, including sequences which correspond to the previously characterized beta 1-tubulin gene. The B. pahangi beta 2-tubulin gene was isolated by selecting clones which hybridize to the H. contortus beta-tubulin gene but which do not hybridize to the beta 1-tubulin gene. A partial sequence of the beta 2-tubulin gene confirms that it codes for a distinct beta-tubulin. Southern hybridization analyses show that the beta 2-tubulin sequence exists as a single copy gene within the B. pahangi genome. Expression of the beta 2-tubulin gene is developmentally regulated and the message is found predominantly in adult male worms, whereas the beta 1-tubulin gene is expressed in microfilariae and approximately equal levels of the transcript are found in male and female adult worms. During mRNA maturation the beta 1-tubulin mRNA of microfilariae and adult worms acquires a trans-spliced leader identical to the SL1 of Caenorhabditis elegans. PMID- 1741016 TI - Cloning of a cDNA encoding phosphoenolpyruvate carboxykinase from Haemonchus contortus. AB - Biochemical and metabolic data have led to the conclusion that the enzyme phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) contributes to a critical point of divergence in energy conservation pathways between mammals and nematodes. To facilitate the determination of the molecular basis for host vs parasite differences in PEPCK, we have cloned a cDNA encoding this enzyme from a parasitic nematode of ruminants, Haemonchus contortus. H. contortus PEPCK was cloned by functional complementation of a PEPCK-, malic enzyme- strain of Escherichia coli (E1786) using an egg stage H. contortus cDNA library in lambda ZAPII. Selection was for growth on malate as the sole carbon source (malate+ phenotype). We isolated a plasmid, pPEPCK, which reproducibly confers a malate+ phenotype in E1786. The sequence of the 2.0-kb EcoRI insert of pPEPCK predicts a 612-amino acid protein which shows about 74% similarity to Drosophila melanogaster and chicken PEPCK. Extracts of E1786[pPEPCK], but not E1786, contain IDP- or GDP-dependent PEPCK enzyme activity. Sequence analysis revealed that the open reading frame (ORF) in pPEPCK lacked a 5' initiation codon and was probably expressed as an in-frame fusion protein with beta-galactosidase. A strategy combining library screening with PCR analysis of positive clones led to the identification of a clone encoding 6 additional NH2-terminal amino acids, including a Met, which, by comparison with known PEPCK amino acid sequences, is likely to be the translation initiation site. PMID- 1741017 TI - Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. AB - Experimental evidence indicates that tubulin is the site of action of the anthelmintic benzimidazoles. Furthermore, certain residues of beta-tubulin seem to be critical for this mechanism. Although the benzimidazoles selectively affect nematode vs. mammalian beta-tubulin, the molecular basis for this differential action is not known. To enhance our understanding of this phenomenon, and to provide the basis for investigating benzimidazole resistance in parasitic nematodes, we undertook the cloning of beta-tubulin cDNAs from the ruminant parasite, Haemonchus contortus. We have cloned and sequenced three beta-tubulin cDNAs from this organism, beta 12-16, beta 12-164, and beta 8-9. The first 2 differ at only 23 nucleotides, which give rise to 4 amino acid changes. beta 8-9 represents a different isotype class from the other two, since it differs extensively in the carboxyterminus. By comparing the sequences of these and other nematode beta-tubulins with mammalian beta-tubulins, several regions of consistent difference can be recognized; the functional significance of these regional differences has not been defined. Sequences very similar or identical to beta 8-9 and beta 12-16 are present in both benzimidazole-sensitive and benzimidazole-resistant populations of H. contortus. However, it appears that drug-resistant organisms may differ in the presence of a gene product which is closely related to beta 8-9. PMID- 1741018 TI - Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. AB - Merozoites of the malaria parasite Plasmodium falciparum possess on their surface proteolytically processed fragments of the merozoite surface protein-1 (MSP1). Secondary processing of one of these fragments, MSP1(42), always occurs prior to, or at the point of successful erythrocyte reinvasion. It is shown that a product of this secondary processing, MSP1(33), is shed in the form of a noncovalently associated complex with a number of other proteins, including the MSP1-derived species MSP1(38) and MSP1(83). Secondary processing of MSP1(42) is inhibited by the chelating agents ethylenediaminetetraacetic acid (EDTA) and ethyleneglycol bis-(beta-aminoethyl ether)-tetraacetic acid (EGTA), and this inhibition is reversible by addition of excess calcium. Secondary processing occurs in preparations of washed, disrupted merozoites, and is inhibited by the protease inhibitors phenylmethylsulphonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP), indicating that the protease responsible is a membrane-associated serine protease. PMID- 1741019 TI - The role of calcium in the invasion of human erythrocytes by Plasmodium falciparum. AB - The role of calcium in the invasion of human erythrocytes by Plasmodium falciparum merozoites has been investigated using a variety of techniques. It has been demonstrated using calcium-depleted medium that invasion is dependent upon the presence of calcium and that neither magnesium, manganese or zinc may substitute for it, suggesting that the effect is calcium specific and not dependent upon a non-specific, charge-based mechanism. Using resealed erythrocyte ghosts and altering the internal and external concentrations of calcium and the chelator EGTA, it has been shown that the role of calcium in invasion, at least as far as the target cell is concerned, is in the extracellular environment. Similarly, loading either the schizont-infected, or target erythrocyte with the membrane permeant calcium chelator Indo-1, at concentrations sufficient to chelate approximately 100 times the concentration of resting cell calcium, produced no change in the parasite invasion rate. Consequently we conclude that calcium plays an extra-cellular role in merozoite invasion of the human erythrocyte. PMID- 1741020 TI - Repeat structures in a Plasmodium falciparum protein (MESA) that binds human erythrocyte protein 4.1. AB - The mature-parasite-infected erythrocyte surface antigen (MESA, also known as PfEMP-2 and pp300) of Plasmodium falciparum is a phosphoprotein of approx. 250 300 kDa that is exported from the parasite to the erythrocyte membrane skeleton where it binds to protein 4.1. Determination of the primary sequence of MESA reveals that it is encoded by 2 exons, a structure common to other exported proteins of P. falciparum. The MESA protein is heavily charged and contains 7 distinct repeat regions that compose over 60% of the protein. The predicted secondary structure suggests that MESA is a fibrillar protein and it shows similarity to a number of cytoskeletal and neurofilament proteins, including myosin, a protein that itself binds to protein 4.1. PMID- 1741021 TI - Sequence of a 16-kilodalton sexual stage and sporozoite surface antigen of Plasmodium reichenowi and comparison with Pfs16 of Plasmodium falciparum. PMID- 1741022 TI - DNA recombination associated with short direct repeats in Leishmania mexicana M379. PMID- 1741023 TI - Isolation and characterization of genomic clones encoding a serine-rich Entamoeba histolytica protein. PMID- 1741024 TI - Genome project faces commercialization test. PMID- 1741025 TI - Indirect costs. Dingell probe expands. PMID- 1741026 TI - US science budget. Seven percent solution: too good to be true? PMID- 1741027 TI - Transmembrane signalling. Pivots or pistons? PMID- 1741028 TI - Eye development. Function for Ras in sight. PMID- 1741029 TI - Prune function? PMID- 1741030 TI - Genetics and speciation. AB - Called the "mystery of mysteries" by Darwin, speciation is still a little understood area of evolution. Genetic analysis, however, has yielded new generalizations about speciation and suggests promising avenues of research. PMID- 1741031 TI - Evolution of king crabs from hermit crab ancestors. AB - King crabs (Family Lithodidae) are among the world's largest arthropods, having a crab-like morphology and a strongly calcified exoskeleton. The hermit crabs, by contrast, have depended on gastropod shells for protection for over 150 million years. Shell-living has constrained the morphological evolution of hermit crabs by requiring a decalcified asymmetrical abdomen capable of coiling into gastropod shells and by preventing crabs from growing past the size of the largest available shells. Whereas reduction in shell-living and acquisition of a crab like morphology (carcinization) has taken place independently in several hermit crab lineages, and most dramatically in king crabs, the rate at which this process has occurred was entirely unknown. We present molecular evidence that king crabs are not only descended from hermit crabs, but are nested within the hermit crab genus Pagurus. We estimate that loss of the shell-living habit and the complete carcinization of king crabs has taken between 13 and 25 million years. PMID- 1741032 TI - Movement selection in advance of action in the superior colliculus. AB - The primate superior colliculus contains a map of saccadic eye movements. Saccades are high-velocity eye movements to selected targets in the visual field, but little is known about the neural mechanisms responsible for target selection or the related problem of choosing a particular movement from the oculomotor repertoire. Two classes of neurons have been described in the superior colliculus which show bursts of activity before the saccade: discrete bursters display a vigorous pre-saccadic burst and prelude bursters show low-frequency activity as a prelude to burst onset. We have designed experiments to test whether prelude activity is related to saccade selection. Our tasks use a cue to specify which of two physically identical visual stimuli is the goal of an impending saccade. This cue is spatially and temporally isolated from the potential targets as well as from visual cues signalling movement initiation. Our results show that prelude activity occurs shortly after information is available for correct saccade selection and, more importantly, the activity is predictive of saccade choice. The results thus suggest that the superior colliculus participates in the process of saccade selection. PMID- 1741033 TI - Evidence from mosaic analysis of the masculinizing gene her-1 for cell interactions in C. elegans sex determination. AB - Sex in Caenorhabditis elegans is determined by a regulatory cascade of seven interacting autosomal genes controlled by three X-linked genes in response to the X chromosome-to-autosome (X/A) ratio. XX animals (high X/A) develop as self fertile hermaphrodites, and XO animals (low X/A) develop as males. The activity of the first gene in the sex-determining cascade, her-1, is required for male sexual development. XO her-1 loss-of-function mutants develop as self-fertile hermaphrodites, whereas XX her-1 gain-of-function mutants develop as masculinized intersexes. By genetic mosaic analysis using a fused free duplication linking her 1 to a cell-autonomous marker gene, we show here that her-1 expression in a sexually dimorphic cell is neither necessary nor sufficient for that cell to adopt a male fate. Our results suggest that her-1 is expressed in many, possibly all, cells and that its gene product can function non-autonomously through cell interactions to determine male sexual development. PMID- 1741034 TI - Yeast RAD14 and human xeroderma pigmentosum group A DNA-repair genes encode homologous proteins. AB - Xeroderma pigmentosum (XP), a human autosomal recessive disorder, is characterized by extreme sensitivity to sunlight and high incidence of skin cancers. XP cells are defective in the incision step of excision repair of DNA damaged by ultraviolet light. Cell fusion studies have defined seven XP complementation groups, XP-A to XP-G. Similar genetic complexity of excision repair is observed in the yeast Saccharomyces cerevisiae. Mutations in any one of five yeast genes, RAD1, RAD2, RAD3, RAD4, and RAD10, cause a total defect in incision and an extreme sensitivity to ultraviolet light. Here we report the characterization of the yeast RAD14 gene. The available rad14 point mutant is only moderately ultraviolet-sensitive, and it performs a substantial amount of incision of damaged DNA. Our studies with the rad14 deletion (delta) mutation indicate an absolute requirement of RAD14 in incision. RAD14 encodes a highly hydrophilic protein of 247 amino acids containing zinc-finger motifs, and it is similar to the protein encoded by the human XPAC gene that complements XP group A cell lines. PMID- 1741035 TI - Lactose binding to heat-labile enterotoxin revealed by X-ray crystallography. AB - Recognition of the oligosaccharide portion of ganglioside GM1 in membranes of target cells by the heat-labile enterotoxin from Escherichia coli is the crucial first step in its pathogenesis, as it is for the closely related cholera toxin. These toxins have five B subunits, which are essential for GM1 binding, and a single A subunit, which needs to be nicked by proteolysis and reduced, yielding an A1-'enzyme' and an A2-'linker' peptide. A1 is translocated across the membrane of intestinal epithelial cells, possibly after endocytosis, upon which it ADP ribosylates the G protein Gs alpha. The mechanism of binding and translocation of these toxins has been extensively investigated, but how the protein is orientated on binding is still not clear. Knowing the precise arrangement of the ganglioside binding sites of the toxins will be useful for designing drugs against the diarrhoeal diseases caused by organisms secreting these toxins and in the development of oral vaccines against them. We present here the three-dimensional structure of the E. coli heat-labile enterotoxin complexed with lactose. This reveals the location of the binding site of the terminal galactose of GM1, which is consistent with toxin binding to the target cell with its A1 fragment pointing away from the membrane. A small helix is identified at the carboxy terminus of A2 which emerges through the central pore of the B subunits and probably comes into contact with the membrane upon binding, whereas the A1 subunit is flexible with respect to the B pentamer. PMID- 1741037 TI - CLONTECH now offers glyceraldehyde 3-phosphate dehydrogenase (G3PDH) and transferrin receptor PCR amplimers and cDNA probes. PMID- 1741036 TI - Selection of single-stranded DNA molecules that bind and inhibit human thrombin. AB - Aptamers are double-stranded DNA or single-stranded RNA molecules that bind specific molecular targets. Large randomly generated populations can be enriched in aptamers by in vitro selection and polymerase chain reaction. But so far single-stranded DNA has not been investigated for aptamer properties, nor has a target protein been considered that does not interact physiologically with nucleic acid. Here we describe the isolation of single-stranded DNA aptamers to the protease thrombin of the blood coagulation cascade and report binding affinities in the range 25-200 nM. Sequence data from 32 thrombin aptamers, selected from a pool of DNA containing 60 nucleotides of random sequence, displayed a highly conserved 14-17-base region. Several of these aptamers at nanomolar concentrations inhibited thrombin-catalysed fibrin-clot formation in vitro using either purified fibrinogen or human plasma. PMID- 1741038 TI - Ideas for the immunologist. PMID- 1741039 TI - Ideas for the immunologist. PMID- 1741040 TI - DNA fingerprinting. FBI gives in on genetics. PMID- 1741041 TI - Animal experimentation. Swiss public backs research. PMID- 1741042 TI - Animal research. Airlines vs activists. PMID- 1741043 TI - Gene therapy panel. NIH merger to shorten review. PMID- 1741044 TI - Genome project. Patents, round two. PMID- 1741045 TI - Pharmaceutical industry. Glaxo benches top manager. PMID- 1741046 TI - Patent protection. Canadian drug firms boost R&D spending. PMID- 1741047 TI - UK fund created. HIV compensation. PMID- 1741048 TI - DNA profiling and the police. PMID- 1741049 TI - Gene therapy. PMID- 1741050 TI - Disallowing direct costs. PMID- 1741051 TI - Radiation biology. Alpha-particle after effects. PMID- 1741052 TI - Palaeoanthropology. Old bones match old stones. PMID- 1741053 TI - AIDS vaccine developments. PMID- 1741054 TI - AIDS vaccine developments. PMID- 1741055 TI - AIDS vaccine developments. PMID- 1741056 TI - Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. AB - The primary sequence of two components of the dystrophin-glycoprotein complex has been established by complementary, DNA cloning. The transmembrane 43K and extracellular 156K dystrophin-associated glycoproteins (DAGs) are encoded by a single messenger RNA and the extracellular 156K DAG binds laminin. Thus, the 156K DAG is a new laminin-binding glycoprotein which may provide a linkage between the sarcolemma and extracellular matrix. These results support the hypothesis that the dramatic reduction in the 156K DAG in Duchenne muscular dystrophy leads to a loss of a linkage between the sarcolemma and extracellular matrix and that this may render muscle fibres more susceptible to necrosis. PMID- 1741057 TI - Earliest Homo. AB - The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far. PMID- 1741058 TI - Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene. AB - Glucocorticoids, in conjunction with their cognate receptors, exert negative feedback effects on the hypothalamus-pituitary-adrenal axis, suppressing adrenal steroid secretions. Two types of corticosteroid receptor, distinguishable by their ability to bind corticosterone, have been identified as classical mineralocorticoid (type I) and glucocorticoid (type II) receptors by cloning their complementary DNAs. The type I receptor controls the basal circadian rhythm of corticosteroid secretion. Both receptor types are involved in negative feedback, but the type II receptor may be more important for terminating the stress response as it is the only one to be increased in animals rendered more sensitive to corticosteroid negative-feedback effects. Here we create a transgenic mouse with impaired corticosteroid-receptor function by partially knocking out gene expression with type II glucocorticoid receptor antisense RNA. We use this animal to study the glucocorticoid feedback effect on the hypothalamus-pituitary-adrenal axis. PMID- 1741059 TI - Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. AB - The acquired immunodeficiency syndrome (AIDS) is the late-stage clinical manifestation of long-term persistent infection with the human immunodeficiency virus type 1 (HIV-1). Immune responses directed against the virus and against virus-infected cells during the persistent infection fail to mediate resolution of the infection. As a result, a successful AIDS vaccine must elicit an immune state that will prevent the establishment of the persistent infection following introduction of the virus into the host. The third hypervariable (V3) domain of the HIV-1 gp120 envelope glycoprotein is a disulphide-linked closed loop of about 30 amino acids which binds and elicits anti-HIV-1 type-specific virus neutralizing antibodies. The in vitro characteristics of anti-V3 domain antibody suggest that this antibody could by itself prevent HIV-1 infection in vivo, an idea supported by chimpanzee challenge studies in which protection against the HIV-1 persistent infection seemed to correlate with the presence of anti-V3 domain antibody. Here we directly demonstrate the protective efficacy of anti-V3 domain antibody in vivo and propose that this antibody is potentially useful as both a pre- and post-exposure prophylactic agent. PMID- 1741060 TI - Genetic linkage of Werner's syndrome to five markers on chromosome 8. AB - Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, and patients and their cells show many differences compared with normals. Despite extensive study of the clinical and biochemical features of this disorder, the primary genetic defect remains unknown. We have undertaken a genetic linkage study in an effort to identify the locus of the primary defect. Here we report close genetic linkage of the WS mutation to a group of markers on chromosome 8. PMID- 1741061 TI - Transmission of chromosomal instability after plutonium alpha-particle irradiation. AB - When investigating the biological effects of ionizing radiation on the haemopoietic system, a confounding problem lies in possible differences between the biological effects of sparsely ionizing, low linear energy transfer radiation such as X-, beta- or gamma-rays, and densely ionizing, high linear energy transfer radiation such as alpha-particles. To address this problem we have developed novel techniques for studying haemopoietic cells irradiated with environmentally relevant doses of alpha-particles from a plutonium-238 source. Using a clonogenic culture system, cytogenetic aberrations in individual colonies of haemopoietic cells derived from irradiated stem cells have been studied. Exposure to alpha-particles (but not X-rays) produced a high frequency of non clonal aberrations in the clonal descendants, compatible with alpha-emitters inducing lesions in stem cells that result in the transmission of chromosomal instability to their progeny. Such unexpected instability may have important implications for radiation leukaemogenesis. PMID- 1741062 TI - Renaturation of DNA catalysed by yeast DNA repair and recombination protein RAD10. AB - The RAD10 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of ultraviolet-damaged DNA, and it functions in mitotic recombination. RAD10 has homology to the human excision repair gene ERCC-1. Here we describe the purification of the protein encoded by RAD10 and show that it is a DNA-binding protein with a strong preference for single-stranded DNA. We also show that RAD10 promotes the renaturation of complementary DNA strands. PMID- 1741063 TI - Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli. AB - The Shiga toxin family, a group of cytotoxins associated with diarrhoeal diseases and the haemolytic uraemic syndrome, includes Shiga toxin from Shigella dysenteriae type 1 and verotoxins produced by enteropathogenic Escherichia coli. The family belongs to the A-B class of bacterial toxins, which includes the cholera toxin family, pertussis and diphtheria toxins. These toxins all have bipartite structures consisting of an enzymatic A subunit associated with a B oligomer which binds to specific cell-surface receptors, but their amino-acid sequences and pathogenic mechanisms differ. We have determined the crystal structure of the B oligomer of verotoxin-1 from E. coli. The structure unexpectedly resembles that of the B oligomer of the cholera toxin-like heat labile enterotoxin from E. coli, despite the absence of detectable sequence similarity between these two proteins. This result implies a distant evolutionary relationship between the Shiga toxin and cholera toxin families. We suggest that the cell surface receptor-binding site lies in a cleft between adjacent subunits of the B pentamer, providing a potential target for drugs and vaccines to prevent toxin binding and effect. PMID- 1741064 TI - [The hazard of asplenia: a fulminant sepsis]. PMID- 1741065 TI - [Protocols and standards for family practice]. PMID- 1741066 TI - [Prevention of fulminant septicemia following splenectomy]. PMID- 1741067 TI - [Moerman therapy; evaluation of a 50-year effort]. PMID- 1741068 TI - [Family practice management in urethritis. I. Protocol development]. PMID- 1741069 TI - [Current viewpoints in the development of cystic kidneys in adults]. PMID- 1741070 TI - [3 children with a melanoma of the skin]. AB - Melanoma rarely occurs in children not over 14 years of age. We report on the clinical and pathological features of three patients (two girls and one boy aged 6, 12 and 11 years respectively) from the St Laurentius hospital (Roermond, Netherlands) with melanoma of the skin, in whom the lesions histologically resembled the more frequently occurring spindle and epithelioid cell naevus (SE naevus). In all three cases, metastases were found in the regional lymph nodes. Further metastases were found in the last patient only, after follow-up periods of 29, 8 and 3 years respectively. The problems in distinguishing between melanoma and SE naevus are discussed, on the basis of a literature study and a retrospective analysis of 40 cases retrieved from PALGA (the nationwide computerized pathological archive in the Netherlands) up to and including 1990. As the diagnosis in such cases has important therapeutic consequences, we advise to submit the slides to experienced pathologists in the field, such as the Pathology Panel of the Dutch Melanoma Committee (Nederlandse Melanoom Werkgroep). PMID- 1741071 TI - [Family practice management in urethritis. II. Comparison of clinical management to the protocol]. AB - OBJECTIVE: To describe general practitioners' approach to and management of urethritis in men, and to compare this with a general practice protocol for urethritis. DESIGN: Descriptive. SETTING: General practices in Amsterdam. PATIENTS AND METHODS: In 13 general practices in Amsterdam (23,510 patients, of whom 11,627 men) all episodes of urethritis in men (n = 55) were recorded during one year (complaints, medical management, diagnosis, medication, follow-up). OUTCOME MEASURES: Description of the diagnostic and therapeutic approach and the course of episodes; rough comparison with the urethritis protocol. RESULTS: In 25% the urine sediment was examined; other office tests were rarely performed. In 30 to 40% out of office microbiological tests were performed. In 50% of new diagnoses medication was underdosed, in some cases medication was wrong or not broad enough. In 25% explicit education was offered. In 22% new medication was given in the follow-up encounter. CONCLUSIONS: (Comparison with protocol.) Urine sediment examination as an effective test is performed insufficiently often. Other office tests are rarely performed, in accordance with the protocol. Out of office microbiological tests are performed too often, judged by the few changes of diagnosis and the character of new medication in the follow-up. First treatment is often underdosed and sometimes wrong. First treatment should preferably be broad, adequately dosed and independent of out of office microbiology. Too little education is given concerning the risks of ascending infections in female partners and of HIV infection. The referral rate is very low. It is important to pay attention to the outcome of this study in (postgraduate) education for general practitioners, as they treat the vast majority of urethritis patients. PMID- 1741072 TI - [A newborn infant with an adult-type kidney disease]. AB - Autosomal dominant polycystic kidney disease is described in a premature infant. A review is given of recent diagnostic procedures and consequences of early diagnosis. PMID- 1741073 TI - [Medical activities under adverse conditions. Stimezo Internationaal]. PMID- 1741074 TI - [Exercise-induced anaphylaxis]. PMID- 1741075 TI - [Characterization of the specialty gastroenterology necessary]. PMID- 1741076 TI - [Asthma in children; consensus by pediatric pneumologists on long-term treatment. I. Diagnosis]. PMID- 1741077 TI - [Physician and pharmaceutical industry. II. Postmarketing surveillance]. PMID- 1741078 TI - Learning the art of verbal self-defense. PMID- 1741079 TI - National study. Contrasts in A.I.D.S. care. PMID- 1741080 TI - Don't let doctors intimidate you. PMID- 1741081 TI - Myths & facts ... about fluid imbalance. PMID- 1741082 TI - Treating carbon monoxide poisoning. PMID- 1741083 TI - Managing patients with T.I.A.s. AB - Transient ischemic attacks usually pass quickly, without being diagnosed, but they can be extremely dangerous, even fatal. Here's a guide on how to assess, treat, and educate your TIA patients. PMID- 1741084 TI - "Dr. Dave". PMID- 1741086 TI - More than a number. PMID- 1741085 TI - How vital are vital signs? PMID- 1741087 TI - 25 predictions for perioperative nursing. PMID- 1741088 TI - We couldn't come to terms with Hank ... until he signed a contract. PMID- 1741089 TI - Artificial airways. Resuscitation guidelines you can follow. PMID- 1741090 TI - Avoiding the hazards of look-alike drug names. PMID- 1741091 TI - Laser angioplasty. PMID- 1741092 TI - How to irrigate the ear. PMID- 1741093 TI - Caring for the patient with a C.V.A. PMID- 1741094 TI - The chance to care. PMID- 1741096 TI - Stillborn--and still in my heart. PMID- 1741095 TI - Assessing albumin values. PMID- 1741097 TI - Is certification for you? PMID- 1741098 TI - Gaining recognition. PMID- 1741099 TI - Delayed interval delivery in multiple pregnancies: report of three cases and review of the literature. PMID- 1741100 TI - Inhibin and activin in reproductive biology. PMID- 1741101 TI - A key moment on OH history. PMID- 1741102 TI - Smoking--kiss it goodbye. PMID- 1741104 TI - Guide to EC Directives. Part 4. European Economic Community Commission. PMID- 1741103 TI - Winter blues--seasonal affective disorder. PMID- 1741105 TI - The use of work equipment directive. PMID- 1741106 TI - Duty to inform staff about their rights. PMID- 1741107 TI - History rewritten. PMID- 1741108 TI - Inherent problems of attempts to apply sonar and vibrotactile sensory aid technology to the perceptual needs of the blind. AB - A program of research dealing with two types of sensory aids for the blind--sonar and vibrotactile--is described. Rather than immediately assessing the aids in the mobility context, which has customarily been the case, the aids' capabilities are considered in terms of the major functions of vision, that is, the exteroceptive perception of objects, surfaces, and events of the environment, and the proprioceptive perception of the self, especially the self in relation to the environment. Although sonar aids function very well for localizing objects and for providing acoustic flow specifying self-movement, they do not provide high acuity pattern and shape information due to the long wavelength of ultrasound relative to light. This limitation is considered specifically with respect to the visual accomplishment of recovery of three-dimensional structure/motion from dynamic two-dimensional images. Vibrotactile sensory aids using optical imaging can deliver detailed pattern information to the skin and thus permit assessment of the extent to which a nonvisual system can mediate the recovery of structure problem. However, in even moderately cluttered or complicated environments the skin proves unable to resolve the amount of stimulation it receives vibrotactually. The limitations of sonar and vibrotactile sensory aids are discussed with respect to future sensory substitution efforts as well as their implications for understanding differences and similarities among the senses. PMID- 1741109 TI - Problems to be overcome in high-tech devices for the visually impaired. AB - Many useful applications of technology have been developed for the visually impaired. Many other devices have been developed but remain on laboratory shelves; others again have experienced problems in achieving widespread acceptability due to such problems as training, maintenance, cost, human factors considerations, difficulty in production, and other factors. The present paper examines some of these factors in order to shed light on how such problems might be avoided or solved in the future. To date, more effort in high technology has been brought to bear on problems of the blind than those of the partially sighted, so examples are drawn from the former as well as the latter to illustrate the points made here. PMID- 1741110 TI - Optimal illumination for reading in patients with age-related maculopathy. AB - This study was designed to determine optimal levels of illumination for reading for patients with age-related maculopathy. These patients comprise a large percentage of the low vision population, and illumination has a great impact on their reading ability. For many patients in this study, increased illumination levels improved their performance. Eleven of the 18 patients preferred illumination levels as high as 5920 to 7534 lux (550 to 770 ft-c). This information suggests that illumination levels higher than previously recommended will improve reading speed in most patients with age-related macular degeneration (ARMD). PMID- 1741111 TI - Clinical comparison of corneal diameter and curvature in Asian eyes with those of Caucasian eyes. AB - Anatomical comparisons of the horizontal visible iris diameter (HVID) and the average keratometry (Kav) measurements were made between Asians and Caucasians and also between males and females. It was found that the HVID was significantly different as a function of both culture and gender. Also found was a significant difference in the Kav between males and females but not between Asians and Caucasians. PMID- 1741112 TI - Instrument myopia and the resting state of accommodation. AB - I measured the refractive errors of 210 eyes of 105 subjects by means of the Canon Autoref R-1 and by the Nikon autorefractometer NR7000. I also measured their dark focus of accommodation (DF) with the Canon instrument. Refractive errors had similar effects on the differences between the results produced by the two autorefractometers and on the changes in DF. The differences were statistically significant. Differences between the results produced by the two autorefractometers are thought to be mainly due to instrument myopia, which itself is strongly related to the resting state of accommodation. My results indicate a hyperopic shift in high hyperopes when they are observing through an instrument. PMID- 1741113 TI - Influence of rigid contact lens base curve radius on tear pump efficiency. AB - The effects of rigid contact lens base curve radius changes on tear pump efficiency were determined by measuring oxygen uptake on six with-the-rule corneas (with toricities between 0.37 and 1.00 D) under three conditions: (1) normal open eye, (2) after 5 min of static (without blinking) wear of polymethyl methacrylate (non-gas permeable) contact lenses, and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lenses. The difference between the oxygen uptake rates measured under static and dynamic conditions provides an index of tear pump efficiency. Each subject wore a series of five lenses: fitted on K and 0.05 or 0.10 mm steeper and flatter than the flattest corneal meridian. The overall diameter of all lenses was 8.8 mm, the optic zone was 7.4 mm, the axial edge lift was 0.09 mm, and all other parameters were constant. The contact lens fitted on K was associated with the greatest central corneal oxygen debt under static conditions, whereas the same lens also provided for the best tear exchange with the blink. In addition, better tear exchange was found to be associated with larger palpebral aperture sizes. PMID- 1741114 TI - Mascara pigmentation of the bulbar conjunctiva associated with rigid gas permeable lens wear. AB - We present three patients who were found to have unusual pigmentation of the bulbar conjunctiva. The areas, 1 to 2 mm in size, were translucent with dark black dust-like particles randomly placed within well defined borders. These specks were usually elevated, had a granular texture, and appeared to be overlying pingueculae. All three patients wore rigid gas permeable contact lenses, were found to have either a short tear break-up time or deficient tear aqueous layer, had associated 3:00 and 9:00 o'clock staining, and routinely used heavy mascara and/or eyeliner. In one patient, the areas resolved on discontinuing contact lens wear. The elevated areas may be associated with minor discomfort. We propose that a deficient tear layer and drying adjacent to the lens edge may compromise the conjunctival epithelium and prevent efficient washing of the pigment particles from the conjunctiva, allowing these granules to become embedded in the epithelium. Additional causes of conjunctival pigmentation are discussed. PMID- 1741115 TI - Hypotony and corneal edema secondary to patching in normal eyes. AB - Over the past decade investigators have used patching when studying corneal response to eye lid closure. In these studies, corneal edema was thought to be secondary to hypoxia, and the results were used to predict corneal response to contact lens wear. None of these studies have measured or controlled the intraocular pressure (IOP) during eye patching. Reports in the literature indicate that hypotonous and hypertensive events may induce corneal edema. In order to evaluate the IOP and corresponding corneal changes, measurements were made on subjects with patched eyes. Thirty subjects were unilaterally patched and randomized into tight and light patch groups to maintain complete lid closure for 4 h. Measurements of IOP and corneal thickness (CT) were made at baseline and at hourly intervals. The contralateral eye served as the control for each subject. Our results indicate a significant decrease in IOP and a corresponding increase in CT in the tight patched group as compared to the light patch group, and baseline controls. These results suggest that the corneal edema which results from patching of the eye may be due to hypotony, or a combination of factors affecting corneal function, rather than hypoxia. PMID- 1741117 TI - Report of the section on binocular vision and perception at the American Academy of Optometry. PMID- 1741116 TI - Fourth century visual science. PMID- 1741118 TI - Statistics Notebook: entry III.E: statistical significance and significance level, and entry III.F: P value. PMID- 1741119 TI - Field defects in diabetic patients. PMID- 1741120 TI - Varied clinical spectrum of necrobiotic xanthogranuloma. AB - Four cases are presented that illustrate a wide spectrum of ophthalmologic and systemic features of necrobiotic xanthogranuloma (NXG). Case 1 initially had signs of Cogan syndrome, and then developed chronic lymphocytic leukemia. Case 2, the first case of NXG to undergo autopsy, had progressive cicatricial lid retraction and corneal perforation. Case 3 had a more typical presentation of diplopia and blepharoptosis caused by orbital and periorbital infiltrative masses. Case 4 had nondeforming periocular skin lesions over a 6-year period. In all four cases, the diagnosis was made on the basis of characteristic histopathologic and laboratory findings. Although the cause of NXG is still obscure, in many cases it appears to be a forerunner of lymphoproliferative diseases. PMID- 1741121 TI - Paraneoplastic pemphigus, cicatricial conjunctivitis, and acanthosis nigricans with pachydermatoglyphy in a patient with bronchogenic squamous cell carcinoma. AB - A 77-year-old man with chronic conjunctivitis, acanthosis nigricans with pachydermatoglyphy, and pemphigus-like mucocutaneous lesions was found to have a well-differentiated bronchogenic squamous cell carcinoma. Histopathologic and immunofluorescence studies confirmed the diagnosis of paraneoplastic pemphigus. Skin lesions resolved with oral prednisone and azathioprine therapy, but the conjunctivitis and mucous membrane erosions persisted. The conjunctiva later became scarred with foreshortening of the fornices and development of symblepharon. External beam irradiation arrested the growth of the tumor but did not have any effect on the diseased conjunctiva and other mucous membranes. This case demonstrates that cicatrizing conjunctivitis with bullous mucocutaneous lesions may be a clinical sign associated with an occult neoplasm. PMID- 1741122 TI - Ocular and adnexal findings in patients with facial microsomias. AB - The authors reviewed the ocular findings in 49 patients with facial microsomias not considered part of a known syndrome. Five patients had bifacial microsomia, and 44 patients had hemifacial microsomia. These patients were evaluated in the Craniofacial Clinic in the Division of Pediatric Ophthalmology at Children's Hospital of Philadelphia between the years 1979 and 1989. Ocular or adnexal abnormalities were present in 67% of patients. Visual loss was present in 8% of eyes. Amblyopia was present in 16% of patients. Significant refractive errors were present in 27% of patients, and anisometropia was documented in 8%. Strabismus was present in 22% of patients, and significant lid and adnexal abnormalities were seen in 41%. Because ocular or adnexal findings present in a significant percentage of patients with more mild forms of facial microsomias, regular examinations to uncover and treat these abnormalities are recommended. PMID- 1741123 TI - Diagnostic value and limitations of orbital biopsy in Wegener's granulomatosis. AB - Patients with Wegener's granulomatosis may present with ophthalmic involvement in either the classic or limited forms. Although the overall clinical picture and serologic testing for antineutrophil cytoplasmic antibody (ANCA) are important, biopsy is often necessary for a definitive diagnosis. Accurate interpretation of these orbital biopsies is essential. The authors reviewed the histopathologic features of 13 orbital biopsies in patients with well-documented Wegener's granulomatosis. The classic triad of vasculitis, tissue necrosis, and granulomatous inflammation was seen in 7 of 13 biopsies (54%). Vasculitis in combination with other microscopic findings was seen in 4 of 13 (31%) biopsies. Giant cells were seldom seen. Two biopsies showed only perivascular infiltrates. Based on this study, it appears that a spectrum of histopathologic features can be seen in orbital biopsies in Wegener's granulomatosis. This study underscores the importance of clinical correlation, the application of the ANCA test, and comparison with extraorbital biopsies, if available, when interpreting orbital biopsies in the diagnosis of Wegener's granulomatosis. PMID- 1741124 TI - Diagnostic value of anti-neutrophil cytoplasmic antibodies in scleritis associated with Wegener's granulomatosis. AB - Serum antineutrophil cytoplasmic antibodies (ANCAs) are a sensitive and specific marker for generalized Wegener's granulomatosis. However, ANCA sensitivity and specificity in identifying patients in whom ophthalmic signs constitute the presenting or only definitive manifestation of Wegener's granulomatosis have not been tested. The authors report on 7 patients in whom scleritis was the initial manifestation leading to the diagnosis of Wegener's granulomatosis. Six had the limited form of Wegener's granulomatosis. Results of serum ANCA tests were positive in all these patients. In contrast, the serum ANCA was negative in 54 patients with ocular inflammation due to other disorders; 16 of these patients had scleritis. Serial ANCA titers reverted to normal in only two of the four patients with Wegener's granulomatosis who attained clinical remission. One of the patients who did not revert to normal experienced relapse 2 months after discontinuation of therapy. Antineutrophil cytoplasmic antibodies appear to be both sensitive and specific for Wegener's granulomatosis-associated scleritis, and testing is useful in the evaluation of patients with scleritis. PMID- 1741125 TI - Surgical management of nasolacrimal duct obstruction in patients with Wegener's granulomatosis. AB - The treatment of symptomatic nasolacrimal duct obstruction in patients with Wegener's granulomatosis is controversial. Dacryocystorhinostomy has been effective in patients with long-standing quiescent disease but has been complicated by the formation of nasal-cutaneous fistulas in others. Dacryocystectomy may be an alternative if epiphora is absent. The authors report 13 lacrimal bypass surgeries in 9 patients with Wegener's granulomatosis; there were 10 operations with adequate follow-up and 6 surgical successes. Failure was related to a history of dacryopyocele, localized disease activity in the nose and upper airway, extensive periorbital disease, the use of non-maintenance therapy to contain disease activity, and prior surgical failure. The authors' experience suggests that dacryocystorhinostomy is therapeutically viable in patients with Wegener's granulomatosis; intervention is optimal when the disease is quiescent without medication and is probably reasonable if activity is controlled with maintenance therapy. Anticytoplasmic antibody titers are useful to guide the timing of elective surgery. PMID- 1741126 TI - Effect of topical mitomycin C on glaucoma filtration surgery in monkeys. AB - In this study, an experimental model of glaucoma filtration surgery was used to evaluate the clinical and histologic effects of a single intraoperative topical application of mitomycin C. Argon laser treatment to the trabecular meshwork produced sustained elevation of intraocular pressure in monkeys. Eight eyes of four animals were randomly assigned to receive topical mitomycin C or balanced salt solution at the time of full-thickness sclerostomy. Surgical success was substantially increased in four of five eyes that received mitomycin C when compared with three eyes that received topical balanced salt solution. Mitomycin C was also effective in prolonging surgical success in two eyes that had previously undergone surgery and failed. No significant ocular toxicity was observed in eyes treated with mitomycin C. Histologic examination of mitomycin C treated eyes showed patent sclerostomies and hypocellular, well-formed bleb cavities. A single intraoperative application of mitomycin C has a marked effect on postoperative wound healing after filtration surgery in monkeys. PMID- 1741127 TI - Retinal hemangioblastoma. A histologic, immunohistochemical, and ultrastructural evaluation. AB - The authors evaluated the histologic, immunohistochemical, and ultrastructural characteristics of two eyes with retinal hemangioblastoma from patients with von Hippel-Lindau and von Hippel disease. Results of histologic evaluation showed the eyes to have degenerative changes and residual retinal hemangioblastoma. Immunohistochemical stains performed for MAC-387, factor XIIIa, lysozyme, alpha 1 anti-chymotrypsin (histiocyte markers), factor VIII-associated antigen, ulex europeaus (endothelial markers), neuron-specific enolase, chromogranin, neurofilament (neuroectodermal/neural/neuroendocrine markers) and glial fibrillary acid protein (glial marker) showed normal retinal vascular endothelium, neurons, and glial cells to stain where expected. Vascular endothelium in the retinal hemangioblastomas stained for factor VIII and ulex europeaus. Interstitial cells in the stroma of the tumors failed to stain for the histiocyte markers, chromogranin, and neurofilament. The stromal cells stained for glial fibrillary acid protein and neuron specific enolase. Ultrastructural findings in both eyes included endothelial/pericyte-lined vascular channels, elongated stromal cells, and plump, vacuolated stromal cells with ultrastructural features consistent with glial cells. This study supports the concept that retinal hemangioblastoma is composed of a proliferation of capillaries and glial cells. PMID- 1741128 TI - Immunohistochemical evidence for IgA1 involvement in Graves ophthalmopathy. AB - Orbital muscle, adipose tissues, and periorbital muscle from 11 patients with Graves ophthalmopathy were studied with in situ assays using monoclonal antibodies for IgA1, IgA2, IgM, and IgG. Tissue biopsies were taken from varied extraocular muscles and orbital sites. All cases were from patients with severe disease or disease of long duration. Control specimens of extraocular muscle tissues were obtained from nine patients treated for unrelated orbital disorders. Only connective tissue associated with the extraorbital muscles and periorbital muscles showed any reactivity. Of the muscle tissue obtained from patients with Graves disease all exhibited IgA1 positive staining of the endomysium and perimysium, without staining of the muscle fibers themselves. Parallel sections of orbital muscles reacted with anti-IgA2 or anti-IgM antibody failed to demonstrate staining. Control extraocular muscle tissue did not stain with anti IgM and one control muscle of seven reacted minimally with anti-IgA2. Some reactivity with anti-IgA1 was seen in four of the seven control muscles but this was qualitatively much less than that of muscle tissue from patients with Graves disease. Monoclonal anti-IgG did not stain tissue from the six Graves specimens and three control specimens tested. PMID- 1741129 TI - Inadequate inferior cul-de-sac in the anophthalmic socket. AB - A retrospective review of preoperative findings and postoperative results of conjunctival cul-de-sac fixation surgery performed on 12 patients with acquired anophthalmos and an inadequate inferior conjunctival cul-de-sac was performed. Patients with inadequate conjunctiva or other subconjunctival cicatricial shortening of the inferior cul-de-sac were not suitable candidates for conjunctival cul-de-sac fixation surgery and therefore were excluded from this retrospective study. Only those patients with adequate conjunctiva and loss of inferior cul-de-sac fixation to the lower eyelid retractor complex were selected. Clinical evaluation and theoretical anatomical analysis of this group preoperatively suggested that the absent inferior conjunctival cul-de-sac fixation could allow the intraconal orbital fat to migrate anteriorly, compromising the inferior fornix and prolapsing the conjunctiva of the cul-de-sac superiorly. Surgical correction required direct fixation of the conjunctival cul de-sac to the periosteum immediately posterior to the inferior orbital rim. No externalized sutures or stents were needed to recreate the inferior conjunctival cul-de-sac. All 12 patients had improved ability to retain a prosthetic eye postoperatively. However, two patients had minimal postoperative lower eyelid retraction and an additional two patients had minimal lower eyelid entropion after surgery. Secondary surgery was not required in any patient. PMID- 1741130 TI - American Academy of Ophthalmology 1991 presidential address. PMID- 1741131 TI - Pan-American Association of Ophthalmology 1991 presidential address. PMID- 1741132 TI - Joint meeting American Academy of Ophthalmology and Pan-American Association of Ophthalmology: 1991 keynote address. Barbarians at the gates: medicine, money, and morality. PMID- 1741133 TI - An evaluation of optic disc and nerve fiber layer examinations in monitoring progression of early glaucoma damage. AB - From annual examinations of 813 ocular hypertensive eyes, the authors compared optic disc and nerve fiber layer photographs in 2 age-matched subgroups: 37 eyes that converted to abnormal visual field tests at the end of a 5-year period and 37 control eyes that retained normal field tests. Disc change was detected in only 7 of 37 (19%) converters to field loss and in 1 of 37 (3%) controls. Progressive nerve fiber layer atrophy was observed in 18 of 37 (49%) converters and in 3 of 37 (8%) controls. Serial nerve fiber layer examination was more sensitive than color disc evaluation in the detection of progressive glaucoma damage at this early stage of glaucoma. The evaluation of cup-to-disc ratio or of the nerve fiber layer appearance in the initial photograph taken 5 years before field loss were equally predictive of future field damage. The position of nerve fiber layer defects was highly correlated with the location of subsequent visual field loss. PMID- 1741134 TI - Age-related decline of disc rim area in visually normal subjects. AB - Optic disc parameters and axial lengths were measured in 81 visually normal young and elderly white adults (young [n = 41]: 27.2 +/- 5.7 years versus elderly [n = 40]: 68.8 +/- 8.4 years) using Rodenstock Optic Disc Analyzer and A-scan sonography. Axial lengths correlated positively with optic disc parameters (Spearman correlation analysis: rim area: P = 0.042, disc area: P = 0.052, and cup volume: P = 0.010). Older subjects had a shorter axial length (23.09 +/- 1.02 mm) and smaller disc rim area (1.171 +/- 0.338 mm2) than younger subjects (23.60 +/- 1.15 mm and 1.325 +/- 0.314 mm2; Mann-Whitney U test: P = 0.011 and P = 0.013, respectively). While both axial length and disc rim area declined with age (0.011 mm and 0.003 mm2 per year; Spearman correlation analysis: P = 0.032 and P = 0.020, respectively), the cup-to-disc and rim area-to-disc area ratios appeared to remain relatively constant throughout adult life. The age-related decline of disc rim area is consistent with histologic evidence of age-related decline of ganglion cell axons. The rim area-to-disc area ratio seems less affected by age, and is thus a better parameter to isolate age-related change from disease-related change of optic nerve in a longitudinal follow-up of diseases involving the optic nerve head. PMID- 1741135 TI - 5-FU trabeculectomy. PMID- 1741136 TI - Intraocular pressure-dependent dynamic changes of optic disc cupping in adult glaucoma patients. AB - The authors performed a study of intraocular pressure-dependent changes in optic disc cupping in 17 adults with chronic open-angle glaucoma. Analyses with the Rodenstock Optic Nerve Head Analyzer were performed at baseline low intraocular pressure during therapy, after elevation of intraocular pressure (from therapeutic failure or noncompliance), and after reduction of intraocular pressure with successful therapy. Optic disc cupping increased significantly upon short-term increase of intraocular pressure from baseline of 20.4 +/- 2.5 mmHg to 31.1 +/- 5.9 mmHg. Optic disc cupping reverted to baseline after persistent intraocular pressure reduction to 19.3 +/- 4.8 mmHg. These data demonstrate intraocular pressure-dependent dynamic changes of optic disc cupping in patients with demonstrable glaucomatous optic nerve damage. They underscore the detrimental effect of elevated intraocular pressure and the beneficial effect of intraocular pressure reduction on optic disc cup changes. PMID- 1741137 TI - Retained nuclei after cataract surgery. AB - The authors reviewed the medical records of 36 patients in whom the nucleus or nuclear fragments were retained in the eye after cataract surgery. In 4 patients, there was no further surgery, and visual acuity deteriorated to counting fingers or worse (mean follow-up time, 14 months). Thirty-two patients underwent vitrectomy to remove the retained, unencapsulated nuclear material. Sixty percent (6 of 10) of patients in whom vitrectomy was performed after 3 weeks had chronic glaucoma on long-term follow-up, whereas this complication developed in only 18% (4 of 22) of patients in whom vitrectomy was performed in less than 3 weeks. Sixty-three percent (21 of 32) of vitrectomy patients had final visual acuity of 20/200 or better after removal of the retained nuclear fragments. The causes of the poorest visual outcome (less than 20/200) included 1 or more of the following: corneal decompensation, chronic inflammation, chronic glaucoma with optic atrophy, and retinal detachment. PMID- 1741138 TI - Posterior continuous curvilinear capsulorhexis. An experimental study with clinical applications. AB - The posterior continuous curvilinear capsulorhexis technique has been advocated in cases of posterior capsule rupture during extracapsular cataract extraction. The authors compared posterior continuous curvilinear capsulorhexis with posterior capsular sharp-edged tears. Two different types of forces were experimentally created on the posterior capsule of 30 human eyes obtained after death: (1) implantation and dialing of posterior chamber intraocular lenses (PC IOLs) and (2) increased intravitreal pressure by injection of balanced salt solution. All posterior capsular tears extended toward the equator, causing major capsular defects. In contrast, the posterior continuous curvilinear capsulorhexis remained intact in all cases. This experimental study proves that in cases where an inadvertent posterior capsular tear occurs, a posterior continuous curvilinear capsulorhexis is useful in preventing further capsular damage. Also, in cases where a posterior capsulotomy is indicated, a smooth edge created by a posterior continuous curvilinear capsulorhexis may be useful to maintain the integrity of the capsular bag for PC IOL capsular implantation. PMID- 1741139 TI - Paraneoplastic pemphigus and ophthalmology. PMID- 1741140 TI - An improved technique for management of dislocated posterior chamber implants. AB - Many techniques for repositioning dislocated posterior chamber implants described in the recent literature involve intricate intraocular manipulation of a needle or other sharp instrument. The author describes an improved sulcus fixation technique, which combines the best features of external and internal approaches. Its main features involve temporary externalization of the haptics for easy and secured placement of suture knots, and subsequent reinternalization of the same haptics through horizontal sclerotomies directly external to the ciliary sulcus for precise fixation of the dislocated posterior chamber implant with consistency. Between May 1989 and December 1990, this technique was successfully used for posterior chamber intraocular lens repositioning in 12 cases. The main advantages of this technique include: (1) easy suture placement, (2) less chance of suture slippage with the secured knots, and (3) avoidance of difficult intraocular maneuvers and possible tissue injury. This improved technique expedites the process of posterior chamber implant repositioning. PMID- 1741141 TI - The Beaver Dam Eye Study. Retinopathy in adults with newly discovered and previously diagnosed diabetes mellitus. AB - The prevalence of diabetic retinopathy was examined in people with newly discovered noninsulin-dependent diabetes mellitus (NIDDM) (n = 50) and in those with previously diagnosed diabetes (n = 395) in a population-based study of people between the ages of 43 and 86 years who lived in Beaver Dam, Wisconsin between 1988 and 1990. Retinopathy was determined from stereoscopic fundus photographs. The prevalence of any retinopathy was 10.2% in those with newly diagnosed NIDDM, none had proliferative retinopathy, and 2.0% had macular edema. These data suggest that asymptomatic people discovered to have NIDDM during epidemiologic studies may not need immediate ophthalmoscopic examination at the time of their diagnosis because they have a relatively low risk of danger of visual loss due to diabetic retinopathy at that time. PMID- 1741142 TI - Central serous chorioretinopathy occurring in patients 60 years of age and older. AB - The authors report on 13 eyes in 13 patients, 60 years of age or older, with idiopathic central serous chorioretinopathy, a condition that typically presents in adults between the ages of 30 and 50 years. In older patients, this condition can easily be mistaken for macular degeneration with subretinal neovascularization. None of the patients in this series had soft drusen, geographic atrophy, or subretinal neovascularization, signs of age-related macular degeneration or other retinal or macular disease. Subretinal neovascularization was not seen either at the time of initial diagnosis or during follow-up. The clinical, biomicroscopic, and fluorescein angiographic characteristics of this entity are described. The clinical course of 7 of these 13 eyes that underwent laser photocoagulation treatment is also described. PMID- 1741143 TI - Visual recovery in two patients after intravenous methylprednisolone treatment of central retinal artery occlusion secondary to giant-cell arteritis. AB - Two patients with central retinal artery occlusions secondary to biopsy-proven giant-cell arteritis lost visual acuity to no light perception but recovered to baseline acuity after treatment with intravenous methylprednisolone at a dose of 15 to 30 mg/kg/day. The potential advantages and theoretical basis of early and aggressive treatment with large-dose intravenous corticosteroids in arteritic central retinal artery occlusion are discussed. PMID- 1741144 TI - Initial 5-fluorouracil trabeculectomy in young patients. AB - The effectiveness of initial trabeculectomy with adjunctive 5-fluorouracil (5-FU) for uncomplicated glaucoma in patients age 40 years or younger at the time of surgery was evaluated retrospectively in a consecutive series of 20 eyes of 20 patients. Fifteen patients had juvenile primary open-angle glaucoma, 4 had pigmentary glaucoma, and 1 had glaucoma associated with angle recession. Mean patient age was 26.8 +/- 9.7 years (range, 13 to 40 years) at the time of surgery. The mean total 5-FU dose administered was 27.8 +/- 8.8 mg (range, 15 to 45 mg). The intraocular pressure (IOP) decreased from 34.4 +/- 11.5 mmHg preoperatively to 10.5 +/- 4.0 mmHg postoperatively after a mean follow-up of 31.1 +/- 17.3 months (range, 11.5 to 70 months). Nineteen eyes (95%) had a postoperative IOP of 20 mmHg or less without pressure-lowering medications. One patient required additional medical therapy to control the IOP. Complications included bleb-related endophthalmitis (2 eyes) and hypotony maculopathy (1 eye). PMID- 1741145 TI - Laser-triggered repetitive fluorescein angiography. AB - Liposome-encapsulated fluorescent dye has been altered to allow full fundus angiography after a single laser shot. By exposing the retinal arteries to laser energy where they emerge at the optic disc nerve head, dye release is elicited simultaneously in all four quadrants of the retina, without choroidal fluorescence, allowing visualization of the retinal microcirculation. Because the quantity of dye release is limited, recirculation does not increase background fluorescence. The procedure can be repeated many times without delay with consistent results. Increasing the laser spot size to 1.5 mm allows consistent dye release at energy densities from 0.5 J/cm2 to 3.4 J/cm2. This refinement will allow direct comparison in primates of this technique and conventional fluorescein angiography. The laser energy delivered to the retina is below suggested levels that may be tolerated by the optic nerve. PMID- 1741146 TI - Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporine therapy. AB - Six patients with rheumatoid arthritis (eight eyes) presented with small paracentral perforating corneal ulcers in otherwise quiet eyes. Initial management in five patients (seven eyes) consisted of systemic immunosuppression and therapeutic tissue adhesive with a bandage contact lens or tectonic keratoplasty. Ulceration recurred in all of these eyes, and recurrent ulcers treated with repeat tectonic keratoplasty or therapeutic tissue adhesive and a bandage contact lens all developed recurrent ulceration. The introduction of topical cyclosporine therapy in five eyes with recurrent corneal ulceration was associated with arrest of keratolysis and rapid re-epithelialization of the ulcer in all cases. One corneal ulcer was successfully treated initially with topical cyclosporine, tissue adhesive, and a bandage contact lens. In patients with rheumatoid arthritis and small paracentral corneal ulcerations or perforations, application of tissue adhesive and a bandage contact lens and introduction of topical cyclosporine may be the preferred initial treatment. PMID- 1741147 TI - Specular microscopic observation of normal human corneal epithelium. AB - The authors analyzed the specular microscopic appearance of normal corneal epithelium, with particular regard to four cell patterns previously identified in pathologic corneas. Corneal epithelia of 75 normal eyes were examined by specular microscopy using a special compound contact lens. There were no elongated or extra large cells, whereas 44.0% and 35.7% of the corneas showed central epithelial nuclei and irregular patterns, respectively. The mean epithelial cell area and corresponding mean coefficient of variation (CV) for each of the corneas were 595.6 +/- 98.8 microns 2 and 30.3 +/- 15.3%, respectively. The values for the endothelium were 325.7 +/- 48.4 microns 2 and 33.6 +/- 6.3%, respectively. Although there was a significant Pearson correlation (r = 0.50, P less than 0.01) between mean endothelial cell area and age, none existed (r = 0.19, P greater than 0.05) between mean epithelial cell area and age, even though there was a relationship (r = 0.35, P less than 0.01) between the mean cell areas themselves. There were no significant relationships among the CV of the epithelium, that of the endothelium, and age. This study presents a powerful new technique and baseline data by which to assess normal corneal epithelium and any aberration. PMID- 1741148 TI - Superficial juvenile granular dystrophy. AB - Seventeen cases of a superficial corneal dystrophy are presented. The lesions are subepithelial, limited mainly to Bowman's layer. This dystrophy, although clinically different from classic granular dystrophy, is pathologically similar to it. Treatment, consisting of superficial keratectomy to 15% to 20% of corneal thickness, did not require lamellar grafting and produced good visual results. A new classification of granular dystrophy is proposed. PMID- 1741149 TI - [The role of combined SPECT studies of regional cerebral blood flow and volume in the detection of intracranial vascular malformations]. AB - Brain perfusion (rCBF) (99mTc--HMPAO) and blood volume (rCBV) (99mTc--RBC) investigations were performed by SPECT on 13 patients with intracranial AVM. In each cases the rCBF revealed a decreased tracer uptake at the site of the AVM. In the rCBV SPECT, abnormal AVM structures with increased radioactivity were detected in 92% of cases. In all of the patients surgical resection of the AVM was also carried out. In the cases where the rCBF disturbance was equal or larger than the rCBV abnormality the surgical complications were more frequent it was concluded that combined rCBF--rCBV method is suitable to detect the AVM-s, and to clarify their haemodynamic effects. It is helpful in planning the surgical intervention, and in the follow-up. PMID- 1741150 TI - [Changes in serum levels of lipid and lipoprotein fractions during breast feeding under the effect of hormonal contraceptives]. AB - During the first 3 months of the full-time lactation the level of the lipid and lipoprotein fractions does not change in the mother's blood. The levonorgestrel contraceptive pills taken during the lactation do not influence considerably the lipid-metabolism either. There is only one minute deviation in the levonorgestrel group, which is the decreasing though not significant change of the HDL level. The contraceptive pills containing levonorgestrel can be given during the lactation without any danger from the point of view of mother's lipid-metabolism, too. PMID- 1741151 TI - [Preparation for elective colon surgery using the mannitol-ceftriaxone method]. AB - The study includes 450 patients undergoing elective colorectal surgery. Patients were divided in three groups. 140 patients were prepared with conventional enema and purgatives and a Neomycin-metronidazole prophylaxis. 160 patients of the second group were prepared with mannitol (10%) oral 12 hours before the operation and a single dose of ceftriaxone (Rocephin) 2 g intravenously 2 hours before surgery. 150 patients of the third group were prepared with mannitol by the same way described above, and a combination of ceftriaxone 2 g i. v. and metronidazole 500 mg. i. v. two hours before the operation. The study proved that the mannitol combined with ceftriaxone provides a sufficient preparation for colorectal surgery within 12 hours prior the operation. The rate of septic complications and septic deaths was higher in the first group then in the two others. The combination of metronidazole used in the third group showed no advantage versus single dose ceftriaxone alone. PMID- 1741152 TI - [Current problems of nursing I]. AB - Doctors don't deal enough with the questions of nursing, in Hungary many of them don't know the current problems, the tendency of developing. It was too late and only the involved crisis called the international medical public opinion's attention to the importance of this question. The elements of activity, which are took for up-to-date at present, were already found at the historical periods of nursing, but these mostly sank into oblivion or came to nought in the stormy periods of history. This happened also in Europe, where was prosperity in the time of century's turn and great regression after the Second World War. The researches of international corporations connected with nursing tried to uncover the causes, make proposals for remending of the troubles so that nursing also can reach the level of medicine. The permanent staff came diluted because losses were retrieved with unskilled labours; countries concentrated on reconstruction of economy, public health was pushed into the background; later during the period of prosperity the development of medical technics made technical assistance from a lot of nurses, who became the doctor's assistant and not the patient's, whose personal necessities were slowly pushed into the background. Nurses massive career-leaving and other portents indicated the unfavourable tendency of changes, and a new conception was prepared on the basis of detailed analysis to solve this problem. PMID- 1741153 TI - [Helicobacter pylori allergy]. AB - A case of a 44 year old woman with antrum gastritis and H. pylori infection was reported. After unsuccessful treatment of the disorder with bismuth and tinidazole, an auto-vaccine was prepared from the bacterium in order to eliminate the infection. After the first injection of the vaccine a generalised urticaria was observed. In the development of the skin eruptions a type I, and a type IV allergic reaction could be demonstrated using the H. pylori specific RAST-test and leukocyte migration inhibition respectively. After eradication of the bacterium by amoxycillin treatment, the clinical signs of both the gastrointestinal and allergic diseases disappeared. PMID- 1741154 TI - [Gallstone ileus after endoscopic sphincterotomy]. AB - The authors report on a case of gallstone ileus developed after endoscopic sphincterotomy (EST). The patient had to be operated and recovered uneventfully after enterotomy. Emphasis is placed on the importance of patient's observation after EST so this rare complication could be revealed in time. PMID- 1741155 TI - [Attempt at reducing the "biographical hiatus" in the life of Samuel Decsy]. PMID- 1741156 TI - [Homeopathy in Hungary]. PMID- 1741157 TI - Cellular localization and T antigen binding of the retinoblastoma protein. AB - Mutation of the retinoblastoma (Rb) gene is found frequently in human sarcomas, lung, bladder and breast carcinomas and is the molecular basis for hereditary predisposition to retinoblastoma. The Rb protein is a nuclear phosphoprotein that is differentially phosphorylated during the cell cycle. Its precise function is unknown but it has been suggested that it may act as a transcriptional regulator or as a regulator of cellular DNA synthesis. The Rb protein forms specific complexes with the oncogenes of three different groups of DNA tumour viruses. We have prepared a new monoclonal antibody to the Rb protein and used it to establish sensitive immunoassays for Rb complexed to T antigen. In SV40-infected and transformed cells these assays showed that Rb enters a trimolecular complex containing p53, Rb and T. A large panel of human tumour cell lines was tested for expression, cellular localization and T-binding activity of Rb using the new antibody. PMID- 1741158 TI - Transformation of normal rat kidney cells by v-K-ras enhances expression of transin 2 and an S-100-related calcium-binding protein. AB - v-K-ras transformants of normal rat kidney cells (KNRK) exhibit cell surface related, transformation-specific properties, including cell-surface fibronectin depletion, induction of anchorage- and density-independent growth, and increased synthesis of transforming growth factors alpha and beta. To search for potential distal effectors of v-K-ras-mediated transformation, we prepared a rabbit antiserum directed against intact KNRK cells to immunoprecipitate and compare proteins from detergent lysates and conditioned media of labeled NRK, KNRK, B77 NRK (a v-src transformant) and ts-371-NRK cells (a Ki-MSV encoding a temperature sensitive p21v-K-ras). Proteins with enhanced expression in both wild-type v-K ras and v-src transformants included a cell-surface phosphoglycoprotein with apparent Mr of 79,000 (79K) modified from an 85K protein observed in NRK cell lysates, a cytoplasmic 47K and a 10K protein, and a 57K secreted glycoprotein. A KNRK-specific 21K membrane-associated protein and secreted 59K and 36K secreted glycoproteins were also detected. The expression of the 36K and 59K proteins best correlated with temperature-dependent activation of the ts-371-NRK p21v-K-ras. Immunoselection of recombinant clones from a KNRK-specific lambda gt11 cDNA library allowed identification of the 59K and 10K proteins as transin 2 and an S 100-related calcium-binding protein identified as p9Ka/42A but not previously associated with oncogenic transformation of rat cells. Transin 2 detection by a cell-derived antiserum may also suggest the presence of specific cell-surface binding sites for this enzyme. PMID- 1741159 TI - Sustained induction of egr-1 by v-src correlates with a lack of fos-mediated repression of the egr-1 promoter. AB - Serum stimulation of quiescent fibroblasts leads to a transient induction of the transcription factor egr-1. However, the induction of egr-1 by v-src was found to be sustained rather than transient. The proto-oncogene fos has been reported to be co-regulated with egr-1 and to repress serum-induced egr-1 expression. We found that c-fos prevents v-src-induced gene expression regulated by the egr-1 promoter. Thus, the sustained induction of egr-1 by v-src could be explained by a lack of c-fos induction by v-src. Consistent with this hypothesis, egr-1 and c fos were co-induced by serum, but not by v-src, in Balb/c 3T3 cells; v-src did not induce c-fos expression in these cells. We propose that sustained expression of egr-1 induced by v-src in Balb/c 3T3 cells is due to a lack of c-fos down regulation of egr-1. PMID- 1741160 TI - Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines. AB - Overexpression of the nuclear phosphoprotein p53 has been detected in many different transformed human cell lines and primary adult tumors. Elevated steady state levels of p53 appear to be the result of an increase in the stability of the protein and, in adult cancers, high levels of the protein are associated with mutation of the p53 gene. In this study, overexpression of p53 was detected in 4 out of 5 human neuroblastoma-derived cell lines. The protein expressed by each of these four lines had a significantly prolonged half-life relative to the p53 protein in immortalized rodent fibroblasts and normal bovine adrenal medullary cells. However, no mutations were detected in the highly conserved regions of the p53 gene in these four neuroblastoma lines and the protein being expressed was not recognized by the mutant-specific anti-p53 monoclonal antibody, PAb 240. Upon retinoic acid-induced differentiation of the LA-N-5 neuroblastoma cell line, the level of p53 protein declined, as did the level of p53 mRNA, but the half-life of the protein remained unchanged. The high level of protein observed in the undifferentiated cell lines appears to result from expression of a stable wild type p53 protein and increased transcription. In contrast, p53 protein was undetectable in two neuroepithelioma-derived cell lines; the p53 gene in one of these lines contained a nonsense mutation, while the other transcribed truncated p53 mRNA. PMID- 1741161 TI - Transcriptional activity of rel family proteins. AB - Our studies originally demonstrated that the v-rel oncoprotein repressed gene expression in chicken lymphoid cells, while it activated transcription in rodent fibroblasts. Here we report that the c-rel protein can activate expression of genes linked to kappa B motifs when low levels of endogenous kappa B-binding activity are present. In contrast v-rel, and to a lesser extent c-rel, inhibit NF kappa B-mediated activation of the human immunodeficiency virus long terminal repeat (HIV LTR) in phorbol ester-stimulated HeLa cells. Competition assays show that v-rel competitively inhibits both NF-kappa B and c-rel-mediated transcriptional activation. Analysis of mutant HIV LTR-chloramphenicol acetyltransferase (CAT) constructs in which all Sp1 or both NF-kappa B elements have been deleted shows that NF-kappa B motifs are required for rel-mediated effects on gene expression. Transforming v-rel mutants compete efficiently with phorbol ester-activated kappa B factors, whereas a transformation-defective mutant of v-rel is impaired in this activity. Taken together, these results strengthen the hypothesis that v-rel functions as a dominant interfering member of rel family proteins. These results also suggest that the ability of v- and c rel to activate or repress gene expression in specific cells may result from their capacity to compete with endogenous rel family proteins whose expression and/or activity are cell-specific. PMID- 1741162 TI - Overexpression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas. AB - The epidermal growth factor receptor (EGFR) and the protein products of c-erbB-2 and c-met proto-oncogenes belong to a family of growth factor receptors with tyrosine kinase activity. In human colonic carcinomas, the expression of the EGFR and c-erbB-2 have been studied at the protein level only, while c-met expression has not been reported. We have examined the mRNA expression of these genes in human normal colorectal mucosa and primary carcinomas. The results demonstrate that the normal mucosa shows highly variable levels of EGFR and c-erbB-2 mRNAs, but expresses consistently low amounts of c-met mRNA. Colorectal carcinomas did not express significantly higher levels of the EGFR and c-erbB-2 mRNAs than the normal mucosa. In contrast, c-met was consistently and significantly overexpressed (mean sixfold) in carcinomas as compared with normal mucosa. Seventy percent of paired normal-tumor specimens showed a tumor to normal c-met mRNA ratio of greater than 4. The expression of c-met mRNA was also enhanced in the adenomas, suggesting that over-expression of this proto-oncogene may have mechanistic significance in the early stages of human colorectal carcinogenesis. PMID- 1741163 TI - cDNA sequence of a growth factor-inducible immediate early gene and characterization of its encoded protein. AB - We report the cDNA sequence of 3CH134, an immediate early gene whose transcription is rapidly and transiently stimulated by serum growth factors. 3CH134 encodes a 367 amino acid protein that does not share significant sequence similarity with any known protein. 3CH134 is inducible through multiple signal transduction pathways, and in the adult mouse is expressed predominantly in the lung. Using affinity-purified antibodies, we have identified the 3CH134 protein in serum-stimulated Balb/c 3T3 cells and determined that it has a short half life. PMID- 1741164 TI - Phosphorylation occurs in the amino terminus of the Raf-1 protein. AB - The ability of the Raf-1 protein to morphologically transform murine fibroblasts can be activated by amino-terminal deletions or substitutions. We have compared the phosphorylation states of full-length and representative transforming and non transforming amino-terminal deletion mutants of the Raf-1 protein using phosphoamino acid analysis and tryptic phosphopeptide mapping. Several [32P]orthophosphate-labeled tryptic phosphopeptides that were present in the full length Raf-1 protein were absent from the highly transforming 22W Raf-1 mutant (lacking 305 amino-terminal residues). Peptide-specific antisera localized Raf-1 phosphorylation sites to several amino-terminal cyanogen bromide and tryptic peptides that are deleted from the 22W protein. A major phosphorylated tryptic peptide of the Raf-1 protein was immunoprecipitated by antiserum directed against amino acid residues 257-275, a highly conserved region of the raf family. This tryptic peptide is entirely deleted from the highly transforming 22W protein. Subtractive Edman degradation and electrophoretic analysis of the immunoprecipitated tryptic peptide indicated that phosphorylation of the Raf-1 protein occurs at serine 259. Multiple phosphorylated tryptic peptide forms were immunoprecipitated by antiserum directed against Raf-1 residues 283-309. The majority of this tryptic peptide is also deleted from the highly transforming Raf 1 mutant 22W. PMID- 1741165 TI - Isolation of azatyrosine-induced revertants from ras-transformed human mammary epithelial cells. AB - Non-transformed revertant clones were isolated from the ras-transformed MTSV1-7 (ras) cell line, after treatment with the antibiotic azatyrosine. Azatyrosine significantly inhibited the growth of the ras-transformed cells but not of the normal MTSV1-7. After 7 days of azatyrosine treatment, approximately 30% of MTSV1 7 (ras) cells survived, and revertant cell lines were selected by random cloning. The azatyrosine-induced revertants (six clones) were considered non-transformed on the basis of (a) their substantially reduced ability to form colonies in soft agar, and (b) their inability to produce tumours in nude mice. Molecular analysis of the revertants revealed that each contains multiple copies of the v-H-ras gene and expresses high levels of v-H-ras mRNA, and all revertants sustain elevated levels of p21ras protein. Thus, the revertant phenotype induced by azatyrosine does not result from inactivation of v-H-ras oncogene or inhibition of its expression. In vivo guanine nucleotide binding to p21ras in the revertant cell lines demonstrated binding of both GTP and GDP, indicating that reversion to the non-transformed phenotype was not due to inability of p21ras to bind GTP. The expression of the human K-rev-1 gene, a known tumour-suppressor gene in ras transformed NIH3T3 cells, was studied in the isolated azatyrosine revertants. All six revertants showed a significant increase in the K-rev-1 transcript levels compared with the ras-transformed MTSV1-7 cells. These results suggest that tumorigenic transformation of human mammary epithelial cells by v-H-ras may be influenced by the level of expression of the tumour-suppressor gene, K-rev-1. PMID- 1741166 TI - A divergent ets-related protein, elk-1, recognizes similar c-ets-1 proto-oncogene target sequences and acts as a transcriptional activator. AB - The ets oncogene superfamily consists of a family of sequence-specific DNA binding proteins that activate transcription. We have previously identified two new members of the ets oncogene superfamily, namely elk-1 and elk-2. In this report we show that the recombinant elk-1 protein expressed in bacteria, like the c-ets-1 proto-oncogene, binds in a sequence-specific manner to Moloney murine sarcoma virus long terminal repeat, E74 target sequences and the PEA3 motif (polyoma enhancer), but does not bind to PU box sequences. Thus analysis of the DNA-binding specificity of ets-related proteins supports the view that different members show similar DNA-binding specificity, which is a general feature of the homeobox proteins. Our data using the chloramphenicol acetyltransferase gene linked to a thymidine kinase promoter containing multimers of the elk-1 target sequence indicates that elk-1 functions as a transcriptional activator. Interestingly, although elk-1 is the most divergent of all the members of the ets gene family, it shows very close similarities with c-ets-1 in some of its sequence-specific DNA-binding specificities. Here, we propose a new function for the elk-1 gene to act as a transcriptional activator of retroviruses and DNA tumor viruses. PMID- 1741167 TI - Temperature-sensitive mutants of p53 associated with human carcinoma of the lung. AB - We have compared the effects of specific point mutations on the tertiary and quaternary structure of the human p53 protein. Eight mutants, each derived from primary resected tissues of lung carcinomas, were expressed in vitro under strictly defined conditions, such that the only known variant was the point mutation present in each p53 mRNA. All the mutations were located in highly conserved domains. The tertiary structure of each mutant protein was investigated by reactivity with anti-p53 monoclonal antibodies directed against conformation dependent epitopes. Quaternary structure was examined by gel filtration. Although all the mutant proteins exhibited abnormal tertiary structures, their quaternary structures appeared similar to wild type, the one exception being p53-tyr135, which contains tyrosine in place of cysteine at residue 135. The conformational phenotype of mutant human p53 was found to be dependent upon (i) the locus of the mutation and (ii) the nature of the amino acid substitution: two different substitutions at residue 273 yielded two mutants with differing structural properties. We have discovered three mutants of human p53 that are temperature sensitive for conformation; one is mutated at codon 273, a 'hotspot' for p53 mutation in human cancer. PMID- 1741168 TI - c-ets-1 DNA binding to the PEA3 motif is differentially inhibited by all the mutations found in v-ets. AB - The proto-oncogene c-ets-1, one of the two cellular sequences transduced by the avian retrovirus E26, encodes for two transcription factors that activate through a purine-rich motif. The v-ets oncogene differs from its cellular progenitor p68c ets-1 (i) by its fusion to gag- and myb-derived sequences in the E26 P135gag-myb ets fusion protein, (ii) by two point mutations, and (iii) by the replacement of the 13 C-terminal amino acids present in c-ets-1 by 16 unrelated residues in v ets. A 35 kDa protein which binds to the purine-rich PEA3 motif in a sequence specific manner has been obtained by expression in Escherichia coli of the 311 carboxy-terminal amino acids of c-ets-1. Using various v-/c-ets-1 chimeric 35 kDa proteins expressed in bacteria, we have shown that all the mutations found in v ets, when introduced into this c-ets-1 protein, diminish or even abolish its sequence-specific DNA binding. These results demonstrate that, in addition to the previously defined 85 amino acids located near the carboxy terminus of the c-ets 1 protein (the ETS domain), other sequences are required for sequence-specific DNA binding. In addition, the c-ets-1 35 kDa polypeptide carrying the two point mutations and the viral-specific carboxy terminus, and thus similar to the v-ets encoded domain of the E26 P135gag-myb-ets, does not bind to the PEA3 motif. PMID- 1741169 TI - Cell type and developmental regulation of the fyn proto-oncogene in neural retina. AB - The product of the proto-oncogene c-fyn (p59fyn) is a non-receptor tyrosine kinase of unknown function. The expression of the p59fyn tyrosine kinase was analysed by immunoperoxidase staining of the different neuronal cell types in the developing chick neural retina. p59fyn was primarily localized in the cell bodies of mature retinal neurons. p59fyn immunoreactivity was most abundant in cell bodies of differentiated ganglion, amacrine and photoreceptor cells. The onset of p59fyn expression in developing photoreceptors occurred coordinately with terminal neuronal differentiation. p59fyn was also found within the outer plexiform layer, which contains synaptic terminals of the photoreceptors. At embryonic stages prior to photoreceptor differentiation, p59fyn was most highly concentrated in the cell bodies of differentiating ganglion and amacrine cells. p59fyn autokinase activity in retinal extracts decreased concomitant with the final stages of maturation of retinal neurons, suggesting that the p59fyn kinase is developmentally regulated. Thus, the expression of p59fyn is regulated in both a developmental and cell type-specific manner. The existence of p59fyn in some of the same neuronal cells as p60c-src suggests the possibility of functional redundancy of these non-receptor tyrosine kinases. PMID- 1741170 TI - The use of local anesthetics in the treatment of chronic pain. AB - Local anesthetics are an important and effective tool in the treatment of patients with chronic pain syndromes. Orthopaedic nurses are in a pivotal position to assess potential problems and intervene where appropriate. This article addresses the pharmacology of local anesthesia, indications for nerve blocks with local anesthetics, and nursing management. PMID- 1741171 TI - Pharmacologic strategies for managing pain in children. AB - Erroneous presumptions about children's reactions to pain have misguided professionals' management of this issue. Recent recognition and understanding of the pain experience in children have prompted research and clinical advances in treatment and care. Considerable study is still needed to further comprehend the difference between the perception and reaction to pain in the pediatric population. PMID- 1741172 TI - Caring for the orthopaedic patient with sickle cell disease. AB - Sickle cell disease (SCD) is an inherited, chronic, painful condition seen primarily in blacks and populations from the Mediterranean and Caribbean areas. The crescent or sickle shaped red blood cells have a shorter lifespan causing severe anemia; they are sticky and easily clump together causing intravascular occlusions which eventually damage vital organs. Providing nursing care for patients with sickle cell disease can be very challenging because of the chronic nature of the illness. Understanding the disease phenomena can facilitate nursing assessments and help nurses individualize care for these clients. PMID- 1741173 TI - Demystifying ethical decision making. AB - Ethical dilemmas frequently occur in the practice of orthopaedic nursing. Nurses, however, are often unsure about how to resolve these dilemmas. The language of ethics remains elusive. Yet, because nurses have a central role in patient care, they need to become more comfortable making ethical decisions related to their practice. This article briefly describes the dialectical process of ethical decision making and demonstrates this process by using a case presentation. Readers are encouraged to put themselves into the role of the bedside nurse in the case, determine what they believe to be the right action, and provide a well grounded rationale for that decision. PMID- 1741174 TI - Development of a nursing automated documentation system. AB - As hospital length of stay has decreased and patient acuity has increased, the nurse is confronted daily with the challenge of managing time between patient care and documentation. Documentation of care has consistently been a time consuming and frustrating part of nursing practice. The nursing shortage has only compounded this problem. St. Joseph's Hospital has creatively begun to facilitate documentation by developing a Nursing Automated Documentation System (NADS) in collaboration with CliniCom, Inc. of Boulder, Colorado. This article documents the development and implementation of the system. PMID- 1741175 TI - Real time ultrasonographic evaluation of the infant hip. AB - Although the technique for ultrasonographic evaluation of the infant hip is difficult to learn, it is a valuable diagnostic tool. In many institutions, hip ultrasonography expands upon and complements the clinical examination and minimizes radiographs. PMID- 1741176 TI - Initial assessment and management of a patient with a gun shot wound of the femur. PMID- 1741177 TI - Problem with the Abbott Lifecare 4100 PC plus infuser. PMID- 1741178 TI - The bones of the midfoot. PMID- 1741179 TI - Lack of evidence of efficacy of cohorting nursing personnel in a neonatal intensive care unit to prevent contact spread of bacteria: an experimental study. AB - Nurse cohorting was investigated in a modern neonatal intensive care unit (NICU). During 99 days bacterial infection and colonization rates were determined in 100 infants experimentally assigned cohort or noncohorted care. Colonizing isolate identity was determined by plasmid profile analyses and biotyping in weekly surveillance cultures. Between Days 2 and 7, 3 infections occurred in cohorted infants but none in noncohorted ones. No secondary spread of infection or definitive colonization cluster occurred. The first colonization rate, at any site, was 0.53/patient-week in the noncohorted and 0.3 to 0.4 in the cohorted units (P greater than 0.05). Colonization ratios with species other than usual skin bacteria in the respiratory tract and with species other than Escherichia coli in the rectum were lower for noncohorted infants. Effective infection control practices in a modern NICU, including alcohol hand antisepsis, should obviate a need for cohorting. PMID- 1741180 TI - Tuberculosis in children infected with human immunodeficiency virus: a report of five cases. PMID- 1741181 TI - Fatal influenza B virus pneumonia in pediatric patients. PMID- 1741182 TI - Transfusion-acquired hepatitis A outbreak from fresh frozen plasma in a neonatal intensive care unit. PMID- 1741183 TI - Pediatric blood culture: comparison of yields using aerobic, anaerobic and hypertonic media. PMID- 1741184 TI - The role of syphilis serology in the evaluation of suspected sexual abuse. PMID- 1741185 TI - Disseminated histoplasmosis as the acquired immunodeficiency syndrome-defining illness in an infant. PMID- 1741186 TI - Fever and spastic quadriparesis caused by Mycoplasma pneumoniae. PMID- 1741187 TI - Antimicrobial therapy for Parinaud's oculoglandular syndrome. PMID- 1741188 TI - Amoxicillin therapy for strep throat. PMID- 1741189 TI - Intraperitoneal and intravenous fluconazole pharmokinetics in a pediatric patient with end stage renal disease. PMID- 1741190 TI - Management of unimmunized contacts of patients with invasive Haemophilus disease. PMID- 1741191 TI - Demographics of community-acquired bacterial infections in hospitalized children. PMID- 1741192 TI - Antimicrobial therapy for suspected sepsis in infants less than three months of age. PMID- 1741193 TI - Fever without source: management of children 3 to 36 months of age. PMID- 1741194 TI - Treatment of skin and skin structure infections. PMID- 1741195 TI - Current antibiotic therapy of community-acquired bacterial infections in hospitalized children: bone and joint infections. PMID- 1741196 TI - Management of community-acquired bacterial pneumonia in hospitalized children. PMID- 1741197 TI - Infections of the urinary tract. AB - There are many options for the treatment of the child with pyelonephritis. Many children can be successfully treated without hospitalization. Appropriate use of studies to image the urinary tract to detect renal damage and treatable anatomical and functional abnormalities is a key aspect of the management of such patients. With appropriate interventions (such as antimicrobial prophylaxis for vesicoureteral reflux or surgery for obstructive lesions), subsequent renal damage can be averted and the morbidity of recurrent infections often can be eliminated. PMID- 1741198 TI - Current management of bacterial meningitis in infants and children. PMID- 1741199 TI - Options for outpatient management of serious infections. PMID- 1741200 TI - Effectiveness of continuous vs. intermittent amoxicillin to prevent episodes of otitis media. AB - The effectiveness of continuous compared with intermittent amoxicillin prophylaxis administered to subjects with a history of recurrent otitis media enrolled during the winter respiratory infection season was assessed in a prospective single blinded clinical trial. Patients with three or more chart documented episodes of otitis media (OM) in the preceding 6 months were enrolled and randomly assigned to each treatment group. Patients in the continuous group received amoxicillin twice a day every day for up to 4 months. During the same period patients in the intermittent group received amoxicillin twice a day only when they developed respiratory symptoms of congestion, runny nose or cough. Among the 30 patients receiving continuous amoxicillin who were followed for at least 3 months, 22 (73%) had no OM episodes and 8 (28%) had one OM episode. Among the 25 patients receiving intermittent amoxicillin for at least 3 months, 13 (52%) had no OM episodes, 8 (32%) had 1 episode and 4 (16%) had 2 episodes. Significantly fewer patients had fewer than 2 OM episodes on continuous compared with intermittent amoxicillin (P less than 0.04). The incidence density was 0.46 episode/120 days at risk in the continuous treatment group compared with 1.10 episodes/120 days at risk for intermittent treatment (P less than 0.03). Among patients 12 months or older the incidence density of OM episodes per 120 days was 3.5 times higher in the intermittent amoxicillin group (0.80) compared with the continuous amoxicillin group (0.23) (P = 0.05). The incidence densities of the continuous vs. intermittent therapy groups did not differ significantly for patients younger than 12 months of age. The findings suggest that continuous amoxicillin prophylaxis may be more effective than intermittent treatment in preventing OM episodes in patients 12 months or older with a history of recurrent otitis media. PMID- 1741201 TI - Chlamydial antibodies in children with lower respiratory disease. AB - Forty-nine of 255 (19.2%) Argentinean children between the ages of 1 and 18 months without evidence of viral or bacterial infections, but with clinical and radiologic evidence of acute lower respiratory distress, had serologic evidence of recent Chlamydia trachomatis infection by the demonstration of specific IgM, seroconversion or 4-fold rise in titer or elevated titers by enzyme immunoassay and the microimmunofluorescence test. Recent C. trachomatis infection was detected in 28 of 166 (16.9%) of children with bronchiolitis and 18 of 89 (20.2%) with pneumonia. Three additional children with bronchiolitis had Chlamydia pneumoniae-specific antibody. There was a significantly higher prevalence of C. trachomatis infection in children living in La Plata city orphanage (26 of 74, 35.1%) than in those attending 2 pediatric hospitals in Buenos Aires (23 of 181, 12.7%) (P less than 0.001). C. trachomatis infection was detected in all age groups up to 18 months. Thirty of 49 infections were in children older than 3 months of age and 16 were in children older than 6 months. These results suggest that C. trachomatis infection may be associated with bronchiolitis and pneumonia in children between the ages of 1 and 18 months of age in Argentina and that a proportion may be horizontally transmitted. PMID- 1741202 TI - Standardized diagnosis of pneumonia in developing countries. AB - The World Health Organization recommends the use of raised respiratory rate and chest wall indrawing to enable health workers in developing countries to diagnose pneumonia. We evaluated the current World Health Organization guidelines for management of the child with cough or difficult breathing in Manila, Philippines and Mbabane, Swaziland using an identical protocol in both countries. Raised respiratory rate was defined as greater than or equal to 50/minute for children ages 2 to 12 months and greater than or equal to 40/minute for children 12 months to 5 years. Chest wall indrawing was defined as inward movement of the bony structures of the lower chest wall with inspiration. In the Philippines raised respiratory rate or chest wall indrawing, when applied by a pediatrician, was found to have a sensitivity of 0.81 and specificity of 0.77 for predicting pneumonia as determined by a pediatrician with the aid of a chest roentgenogram. In Swaziland the sensitivity was 0.77 and the specificity was 0.80. When applied by health workers the sensitivity was similar but the specificity was lower. The current World Health Organization ARI case management guidelines predicted pneumonia with similar sensitivity and specificity in two very different developing countries, the Philippines and Swaziland. PMID- 1741203 TI - Bone and joint infections caused by multiply resistant Staphylococcus aureus in a neonatal intensive care unit. AB - Twenty cases of osteomyelitis and/or septic arthritis caused by multiply resistant Staphylococcus aureus were documented in an Australian tertiary neonatal unit between 1981 and 1987. Eighteen (90%) occurred in the 3 years 1985 to 1987, an incidence of 9.6/1000 admissions in that period. All osteomyelitis and/or septic arthritis occurred in sick premature infants requiring intensive support. Eleven (55%) had a birth weight of less than 1500 g. An intravascular device was the most common portal of entry (14 of 20, 70%). Systemic symptoms were prominent at presentation, with local signs developing later in 18 (90%), usually within a week. Radiologic changes were almost always present by 10 days; radionuclide bone scanning was insensitive and did not hasten diagnosis. Osteomyelitis was multifocal in 11 cases (55%), with the long bones, particularly of the upper limb, most commonly affected. Large joint involvement was uncommon (15%). Intravenous vancomycin for a mean of 32 days was associated with low mortality (1 of 20) and toxicity; surgical drainage was not performed. Follow-up at a minimum of 4 months (mean, 25.5 months) showed residual signs in the affected limb in 30%, none with significantly impaired function. Skeletal infection should be searched for rigorously in neonatal multiply resistant S. aureus sepsis. In the absence of large joint disease, vancomycin therapy alone for a minimum of 3 weeks gives good short term results with minimal toxicity. PMID- 1741204 TI - Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection. AB - Severe infections caused by non-albicans Candida species are being increasingly reported among infants in neonatal intensive care units. To assess relative severity, mortality rates for C. albicans (CA) and C. parapsilosis (CP) infections in one neonatal intensive care unit from 1980 to 1990 were compared. Invasive candidiasis was defined as Candida recovery from a normally sterile body fluid or site with clinical signs of infection. Invasive candidiasis was diagnosed and systemic antifungal therapy initiated in 45 infants, 29 with CA and 16 with CP. No differences were found between CA and CP for birth weight, gestational age, age or weight at onset, presence of necrotizing enterocolitis, gastrointestinal or genitourinary anomalies, death (all causes), prior incidence or duration of antibiotics, parenteral nutrition, steroids or endotracheal intubation. Candida infection as the cause of death was more frequent with CA than CP (7 of 29 vs. 0 of 16; P = 0.034). Infants with CA were more likely to have antecedent thrush (P = 0.007) and perineal Candida dermatitis (P less than 0.02); those with CP were more likely to have vascular catheters at the time of positive culture (P less than 0.02). Though both pathogens occur in similar neonatal intensive care unit infants and can cause severe disease, CA appears more likely to result in death than CP. PMID- 1741205 TI - Long term epidemiological analysis of Citrobacter diversus in a neonatal intensive care unit. AB - A prolonged outbreak of Citrobacter diversus central nervous system infection among hospitalized term infants, peaking in 1979, ceased with establishment of nurse-patient cohorting. The outbreak was attributed to dissemination of an epidemic strain among infants in an antiquated neonatal intensive care unit. When C. diversus colonization recurred within the new neonatal intensive care unit in 1984, cohorting and bacteriologic surveillance were reinstituted. By utilizing biotypes, plasmid profiles and antibiograms, four different C. diversus strains were identified circulating during 1979. Strains recovered between 1984 and 1988 from neonatal intensive care unit infants were similar to those from community acquired sources. A strain considered avirulent in 1979 was found causing bacteremia in two infants (one with central nervous system disease) in 1984 to 1988. During cohorting C. diversus acquisition was 0.019/patient-month; after cohorting ceased it was 0.017/patient-month. Multiple source introductions appeared to occur with different C. diversus strains, some causing infant disease. No efficacy of cohorting was evident. PMID- 1741206 TI - Eight-year school performance, neurodevelopmental, and growth outcome of neonates with bronchopulmonary dysplasia: a comparative study. AB - Eight-year outcome is reported for three groups of preterm infants with bronchopulmonary dysplasia--group 1 with a birth gestation of less than or equal to 31 weeks receiving supplemental oxygen until the equivalent of 36 weeks' gestation, group 2 of the same gestation receiving supplemental oxygen to 28 days postnatal age but not to 36 weeks gestational age, and group 3 with a gestation of greater than or equal to 32 weeks requiring supplemental oxygen for greater than 28 days--and for an individually matched preterm neonatal comparison group and a term peer comparison group for each bronchopulmonary dysplasia group. The subjects all had parents whose mother tongue was English and were matched for gender, mother's education, and father's socioeconomic status, and in the case of the neonatal comparison groups they also were matched for birth gestation and birth weight. Physical growth and psychoeducational and school performance test scores were similar for the three bronchopulmonary dysplasia study groups with the exception of lower intelligence quotient for those receiving supplemental oxygen for the longest time. Children in groups 1 and 2 had outcome scores similar to those of the neonatal comparison group and significantly below those of their peer comparison groups. On multivariate analysis for group 1 children, 61% of the variance of academic achievement was related to lowest recorded pH, father's socioeconomic status, and lowest recorded PaO2. Compared with the peer groups, the study groups continued to show academic delay when the disabled children were excluded from analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741207 TI - Educational outcome of neonatal intensive care graduates. AB - Studies of developmental outcome of neonatal intensive care unit graduates have generally been limited to the first 2 to 3 years of life, with outcome determined by psychometric tests. This study followed neonatal intensive care unit graduates born 1975 through 1983 (n = 457) into the public school system and compared their educational outcomes with those of newborn nursery graduates (n = 656). Outcomes were evaluated by placement in four academic categories: regular classroom, academic problems, speech/language impairment, and major impairment. Educational outcomes for children of both groups were essentially the same. Their placement in the four academic categories were equally affected by nonmedical variables, primarily income (below/above poverty level), race, and sex. Seventy percent of poverty-level children were in one of the three problem categories, compared with 40% of children above poverty level. Neither neonatal intensive care unit treatment nor low birth weight were major predictors of educational outcome. The only clear-cut neonatal intensive care unit effect occurred among children born with sensory or physical impairments. Therefore, in order to reduce poor educational outcomes, follow-up and intervention programs should be targeted primarily to children with diagnosable handicaps and from minority, low-income families. PMID- 1741208 TI - Lack of agreement of tympanic membrane temperature assessments with conventional methods in a private practice setting. AB - An infrared tympanic membrane thermometer (FIRST temp) said to approximate core temperature accurately is being marketed as a noninvasive, quick, and easy-to-use clinical instrument. The determination of tympanic membrane temperatures by this device was compared with the determination of oral, rectal, or axillary temperatures by a conventional glass thermometer. Subjects were patients of a pediatric group practice in Houston, Texas. FIRST temp and conventional temperature determinations on individual patients were completed within 5 minutes of each other. The presence or absence of otitis media was noted by the examining physician. Agreement between the two methods of temperature determination was assessed by calculating limits of agreement within which 95% (+/- 2 standard deviations) of individual differences would fall. The location of conventional thermometer (oral, rectal, axillary), time interval between the two separate measures, and the presence or absence of otitis media were entered into a multiple regression analysis to determine whether these factors influenced the observed differences between the two methods. A total of 144 patients were enrolled in the study; oral comparisons were obtained in 92 (57%) patients, rectal in 35 (24%), and axillary in 29 (19%). The upper and lower limits of agreement between temperature methods were 1.12 degrees C and 0.89 degrees C and the mean difference was -0.12 degrees C. Regression analysis revealed that only the site of conventional thermometer location (oral, rectal, axillary) was a significant predictor of FIRST temp/conventional differences. Each site had a range of agreement greater than 1.65% degrees C; axillary temperatures had the greatest range (-0.94 degree C to +1.30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741209 TI - Appearance of the hymen in prepubertal girls. AB - The recent increase in requests for genital examinations in girls who may have been sexually abused has necessitated detailed information not previously available on normal anatomy of the prepubertal girl. This study was undertaken to document the genital anatomy of 211 girls between the ages of 1 month and 7 years who presented for well child care or nongynecologic complaints and who had no history of sexual abuse. Each child's genitalia was examined and photographed, with findings reported reflecting those observed photographically. The study population consisted of 36% blacks, 33.6% white non-Hispanics, 29.9% Hispanics, and 0.5% Asians. Subjects had a mean age of 21 +/- 20.6 (SD) months. Extensive labial agglutination sufficient to obscure the hymen was noted in 5% (10/211) and partial agglutination in an additional 17% (35/211). A significant difference was noted in hymenal configuration by age, with a fimbriated hymen the most common type (46%) in infants aged 12 months or younger and a crescentic hymen the most common (51%) in girls older than 24 months (P less than or equal to .001). No significant difference was noted in hymen configuration by race. Hymenal bumps (mounds) were observed in 7%, hymenal tags in 3%, vestibular bands in 98%, longitudinal intravaginal ridges in 25%, and external ridges in 15% of subjects in whom the anatomy under study could be visualized. Hymenal notches (clefts) occurred superiorly and laterally on the hymenal rim but none were found inferiorly on the lower half of the hymen. A narrow rounded hymenal ring with a transection was observed in only 1 (0.5%) of 201 subjects and was not considered a normal finding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741210 TI - Girls with fragile X syndrome: physical and neurocognitive status and outcome. AB - The fragile X syndrome, a common X-linked form of mental retardation and autism, affects females as well as males. Previous work has shown that approximately 35% of heterozygotes (women who carry the fragile X gene) demonstrate cognitive impairment. Thirty-two girls, 18 years or younger, who demonstrate the fragile X chromosome were evaluated and compared with 19 sisters who do not demonstrate the fragile X chromosome. Evaluations included a physical examination, behavioral assessment, and intelligence testing. Significant differences (in intellectual, behavioral, and physical features) were seen between the two groups. Twenty-five percent of fragile X-positive girls had an IQ in the mentally retarded range (IQ less than 70) and 28% had an IQ in the borderline range (70 to 84). Prominent ears, shyness, and poor eye contact were significant findings in fragile X positive girls compared with fragile X-negative girls. Thirty-one percent of the fragile X-positive girls had significant attentional difficulties and most of these girls were successfully treated with stimulant medication. The majority of fragile X-positive girls in this study demonstrated significant behavioral and developmental problems which required identification and appropriate treatment. Pediatricians and health care providers should be aware of the frequency and manner with which fragile X affects females in order to initiate cytogenetic studies and treatment when indicated. PMID- 1741211 TI - Early expression of the apolipoprotein (a) gene: relationships between infants' and their parents' serum apolipoprotein (a) levels. AB - The serum concentration of apo(a), the unique apolipoprotein of lipoprotein (a), reflects serum lipoprotein (a) levels. High concentrations are associated with increased cardiovascular risk. Inasmuch as atherogenesis may begin in childhood, the early expression of the apo(a) gene and relationships between serum levels in infants and their parents were explored. Serum apo(a) and lipid profiles were measured in 51 infants when aged 8.5 +/- 2 months. They were from among 1032 consecutively born babies in whom apo(a) levels had been measured on day 2 to 5. Levels in 18 infants were in the top 5% of the neonatal apo(a) distribution and in 33 from below the 95th percentile. Parental values were also assessed. Infants' apo(a) levels (n = 51) at the ages of 2 to 5 days and 8.5 +/- 2.3 months were highly correlated (r = .73, P less than .0001) and increased from an initial median value of 48 U/L (range 1 to 462 U/L) to 100 U/L (5 to 969 U/L) at 8.5 months, and they were then not different from parental levels. Measurements at both times were closely correlated with parental levels. Regression coefficients between 8.5-month levels, and the levels of fathers, of mothers, and the average level of both parents were 0.439, 0.521 and 0.93, respectively (P less than .0001 for each). It is concluded that the gene for the regulation of apo(a) is fully expressed before the age of 1 year. The apo(a) levels in infants during this time track closely and are predictive of parental values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741212 TI - Whole-body cesium 137 activity up to 4 years after the Chernobyl reactor accident in premature newborns, newborns, infants, and children. AB - Cesium 137 activity was measured after the Chernobyl incident in a whole-body radiation counter (4-pi-scintillation counter) in 85 premature and mature newborns (group 1), 174 infants and young children up to 2 11/12 years (group 2), and 48 children between 3 and 8 years (group 3) from Bonn (Germany) and surroundings. In 1987 the mean level of radioactivity in group 2, at 3.7 Bq/kg body weight corresponding to a mean radiation exposure of 11 muSv/y, was lower than that of group 1 (5.8 Bq/kg, 17 muSv/y) and 3 (9.4 Bq/kg, 28 muSv/y). Up to 1990 the values of all groups revealed a continuous decrease. The latest measurements showed mean values of 0.5 Bq/kg (1.5 muSv/y) in group 1, 0.6 Bq/kg (1.8 muSv/y) in group 2, and 0.8 Bq/kg (2.4 muSv/y) in group 3. A comparison with present cesium 137 values and determinations of the end of the 1950s and beginning of 1960s, both in adults, showed good agreement. The effective dose equivalent rates amounted to less than 1% of that from natural radiation exposure. These levels should present no teratogenic risks to the population studied and, while there are theoretical mutagenic risks, the dose is so low that no increase in measurable mutagenic effects should be observed. PMID- 1741213 TI - Pediatric organ donation: the paradox of organ shortage despite the remarkable willingness of families to donate. AB - The 105 pediatric deaths (ages 1 to 16 years) that occurred at Vanderbilt University Medical Center during a 31-month period were reviewed to define the size of the donor pool in the pediatric population and to assess the role of physicians in the procurement of these much-needed organs. Computerized discharge abstracts showed that 57 pediatric patients died without contraindications to organ donation. Manual review of these 57 medical records yielded 46 records suitable for review by Tennessee Donor Services. From this group, 19 eligible donors were identified. All eligible donors died from trauma, intracerebral hemorrhage, anoxic events, or hydrocephalus. Physicians failed to ask one family for permission to donate. All 18 of the families who were asked agreed to donate and organs were successfully procured from all 18 patients. These data suggest that families of pediatric patients are much more willing to agree to donation than the families of adult patients. As a result of this study, a simplified audit process has been developed for hospitals to use in evaluating compliance with required-request legislation. PMID- 1741214 TI - Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children. AB - Impaired linear growth and skeletal maturation associated with chronic glucocorticoid therapy may result from (1) inhibited insulin-like growth factor 1 (IGF-1) activity; (2) impaired type 1 collagen synthesis; or (3) suppressed growth hormone (GH) secretory response to growth hormone-releasing hormone. Each mechanism could potentially be improved by exogenous GH treatment. Seven slowly growing glucocorticoid-treated children received recombinant DNA human GH (0.3 mg/kg/per week) for 6 to 21 (mean 13.1 +/- 4.9) months. Height, weight, IGF-1 activity, glycosylated hemoglobin level, and C-terminal type 1 procollagen level were measured every 3 months and growth velocity was calculated. Skeletal maturation and 2-hour postprandial serum glucose and insulin levels were assessed every 6 months. All patients showed increased growth velocity during treatment with GH. Mean growth velocity increased from 3.43 +/- 0.65 cm/y to 6.72 +/- 0.84 cm/y with GH therapy (P less than .005). Growth velocity standard deviation scores corrected for bone age (P less than .005), IGF-1 levels (P less than .05), and C-terminal type 1 procollagen levels (P less than .005) also increased with GH therapy. C-terminal type 1 procollagen levels correlated well with growth velocity (r = .652) while IGF-1 levels did not (r = .17). Glycosylated hemoglobin levels remained unchanged, but 2-hour postprandial glucose levels rose during GH treatment. Slowly growing glucocorticoid-treated children receiving GH therapy increased growth velocity for 6 to 21 months. Initially diminished C-terminal type 1 procollagen levels rose with GH therapy, a change which corresponded with growth acceleration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741215 TI - Health-risk behaviors and health concerns among young adolescents. AB - This study examined the health concerns and behaviors of 563 adolescents (aged 11 through 14) from a variety of social, racial, and ethnic backgrounds. Behaviors associated with adolescent morbidity and mortality were examined, including sexual behavior, substance use, and injury-related behaviors. Although young adolescents are often viewed as unlikely participants in these risk behaviors, the results of this study suggest that greater attention should be paid to this younger group and their health-risk behaviors. A majority of the sample had tried alcohol and tobacco, and almost a third had used marijuana. Twenty-one percent were sexually active. Prevalence rates varied by social class, race-ethnicity, gender, and age. More than 75% of the sample had visited a physician during the prior year, suggesting an important role physicians may serve as sources of information and positive role models for these young adolescents. The results suggest that we stop viewing young adolescents as naive children and begin to view them as observers of and participants in a changing social environment that has important implications for their current and future health status. Without a realistic appraisal of the young adolescent, we can expect to have little overall effect on the status of adolescent health in the United States. PMID- 1741216 TI - Unusual manifestation of Stevens-Johnson syndrome involving the respiratory and gastrointestinal tract. AB - There are many recognized acute complications of Stevens-Johnson syndrome: however, long-term sequelae involving the respiratory and gastrointestinal tracts are exceedingly rare. We present an 8-year-old girl who developed esophageal stricture and chronic lung disease while recovering from Stevens-Johnson syndrome and discuss these complications with possible mechanisms for their occurrence. PMID- 1741217 TI - Self-administered questionnaire for structured psychosocial screening in pediatrics. AB - Screening for psychosocial risk factors has been limited by lack of a structured approach. The purpose of this study was to assess the utility of a self administered questionnaire compared with routine history as recorded in the medical record in screening for risk factors for dysfunctional parenting in an urban pediatric clinic. English-speaking parents were offered questionnaires in the waiting room. In addition to routine demographic and medical questions, the questionnaires contained standard screening instruments for substance abuse, depression, self-esteem, and social support, as well as questions about domestic violence, homelessness, and parental history of abuse as a child. Medical records were reviewed separately. Of the 114 mothers who returned questionnaires, the response rate for sensitive questions such as income was greater than or equal to 85%. Compared with the medical record, the questionnaire identified significantly more mothers with possible substance abuse, depression, low self-esteem, and/or history of abuse as a child (P less than .01 for each). Compared with what is usually recorded in the medical record, self-administered questionnaires yield substantial additional information regarding psychosocial risk factors for dysfunctional parenting. Such questionnaires should be considered for routine psychosocial screening in clinics serving high-risk populations. PMID- 1741218 TI - Acute prolactin and oxytocin responses and milk yield to infant suckling and artificial methods of expression in lactating women. AB - Breast-feeding is today the major form of infant nutrition in the immediate postpartum period. Despite this, recent trends in modern life-styles have raised obstacles to successful lactation. These include infant illness and maternal responsibilities outside the home, both requiring separation from the mother. While the hormonal dynamics of infant suckling are understood, little is known about the effects of artificial methods of milk expression. A variety of breast pumps exist in the current US market which vary considerably in price and effectiveness. To understand better the ability of these pumps to assist women in the maintenance of lactation, the current study was undertaken to evaluate their effects on milk yield and prolactin and oxytocin release when compared to natural infant suckling. Twenty-three women who were exclusively breast-feeding their infants were randomly assigned to serially use several pumping methods, as well as infant suckling, with blood being taken at 10-minute intervals to determine the hormonal responses. The results reveal variability in the prolactin responses to the artificial pumping methods, with the greatest responses found with an electric pulsatile pump; these responses compare favorably with those of natural infant suckling. Other methods were less successful in causing prolactin elevations. No differences were seen among the methods in the oxytocin response. The results of this study demonstrate striking differences in the ability of breast-pumping methods to produce an acute and sustained prolactin rise in breast feeding mothers. The large discrepancies found suggest the need for further studies in to enable women and health care providers to choose the most appropriate method for milk expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741219 TI - Persistent antinuclear antibodies in children without identifiable inflammatory rheumatic or autoimmune disease. AB - One hundred eight children with musculoskeletal pain considered not to be due to an autoimmune or inflammatory disease had an antinuclear antibody (ANA) test performed. Twenty-four of these children were ANA positive on HEp-2 cell substrate at a screening serum dilution of 1:20. A positive ANA test persisted in 21 of 24 of the patients over a mean time period of 38 months (range 1 to 103 months). No sera from any patient at initial evaluation had anti-DNA antibodies by radioimmunoassay or by indirect immunofluorescence on Crithidia luciliae. One patient recently developed elevated anti-DNA (radioimmunoassay) antibodies but still has a negative assay on C luciliae. Four patients had antibodies to core histones by immunoblotting. None had antibodies to Sm, RNP, Ro (SS-A), or La (SS B) by counterimmunoelectrophoresis. No patient developed an overt inflammatory or autoimmune disease during a mean follow-up period of 61 months (range 13 to 138 months). A child with musculoskeletal pain and a positive test for ANA, but with no clinical evidence at presentation of inflammatory or autoimmune disease, is at low risk of imminently developing such a disease. PMID- 1741220 TI - Chronic illness and mental health problems in pediatric practice: results from a survey of primary care providers. AB - The prevalence of chronic physical illnesses and their association with mental disorders was assessed using data collected by primary care pediatricians. A chronic illness was diagnosed in 1573 (15.6%) of 10,058 children aged 4 to 16 years, 945 (9.4%) of whom had a "serious" disorder, 535 (5.3%) had a minor disorder (hay fever or dermatitis), and 121 (1.2%) had a speech or language disorder. Behavioral problems were identified more often among patients with "serious" disorders than among those without chronic illnesses (2.4% vs 1.7%), as were emotional problems (5.0% vs 3.1%). Among those with "serious" conditions involving the central nervous system, the prevalence of behavioral (5.2%) and emotional (10.4%) disorders was still higher. Although children with "serious" disorders not involving the central nervous system also showed elevated prevalence rates of behavioral (2.1%) and emotional (4.5%) disturbances, this increase did not reach statistical significance. No association with "minor" chronic disorders was found. The negative impact of these mental health problems on the child was more severe when a chronic illness was also present, but referrals for mental health services did not reflect his association. PMID- 1741221 TI - Prolonged periodic breathing: significance in sleep studies. AB - Periodic breathing (PB) is a pattern of breathing that is frequently recognized in infants being studied for possible sleep apnea. Infants presenting to a sleep laboratory over a 3 1/2-year period who had evidence on their initial study of prolonged (greater than 15% of total sleep time) PB were prospectively studied in an effort to determine the significance of this pattern of breathing. Of the 331 infants studied, 40 demonstrated prolonged PB. Sixteen of these infants, who were of 37 weeks' gestation or greater at birth and did not receive pharmacologic therapy, were studied on at least two occasions (group 1). Of the remaining 24 infants, 11 were treated with methylxanthines by their attending physician (group 2), and 13 did not return for sequential studies (group 3). All infants who were of less than 37 weeks' gestation at birth were separately evaluated (group 4). For group 1, who were studied at a mean age of 15 postnatal weeks, there was a mean of 36.4% periodicity which decreased on the second study to 18.0%. By the fourth study, this had decreased to 9.2%. In group 2, there was a mean of 41.3% periodicity during the first study which decreased to 6.4% on the second study. Infants of group 3 had a mean of 31.4% PB on their initial study and the premature infants, group 4, had 30.1% PB. All infants showed a decrease in PB with sequential studies and no infant was known to have died of sudden infant death syndrome or any other disorder in the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741222 TI - Lung involvement in Langerhans' cell histiocytosis: prevalence, clinical features, and outcome. AB - In Langerhans' cell histiocytosis, the prognostic significance of pulmonary disease is controversial. The clinical and radiological features and lung function tests of Langerhans' cell histiocytosis patients presenting to a single tertiary referral center between 1981 and 1987 were reviewed. Age at diagnosis ranged from 2 weeks to 16 years (median 1.7 years) and the male-female ratio was 2.4:1. No child presented with lung involvement alone. In 18 (40%) of 45 patients with multisystem disease there was clinical and/or radiological evidence of lung pathology. Another 6 children (13%) with normal chest roentgenograms had abnormal lung function tests, suggesting subclinical ("occult") involvement. Those with overt lung disease tended to present at a younger than average age (median 0.6 years). The most common functional disturbance was reduced lung or respiratory compliance with reduced lung volumes. Patients with and without lung involvement showed a similar pattern of involvement of other organs, with skin and bone most commonly affected. Of the 45 children with multisystem disease, 38 (84%) survived 2 to 7 years after diagnosis; there was a similar proportion of deaths in children with and without lung involvement. It is concluded that lung involvement occurs in nearly half of young children with multisystem Langerhans' cell histiocytosis but does not adversely affect outcome. PMID- 1741223 TI - Physical examination of patients with cerebrospinal fluid shunts: is there useful information in pumping the shunt? AB - To assess the value of the information derived from pumping the shunt valve in hydrocephalic patients with cerebrospinal fluid shunts, the findings on examination of 200 consecutive patients were recorded prospectively. The status of each shunt was determined on the basis of all available clinical data, and the results of the shunt pumping test were compared to the final status of each shunt for various subsets of the study group. In the most clinically pertinent subsets, the sensitivity of the shunt pumping test in the detection of shunt obstruction was 18% to 20%, and the predictive value of a negative shunt pumping test, indicating shunt patency, was only 65% to 81%. For the hydrocephalic patient with symptoms of shunt malfunction, definitive imaging studies must not be deferred because of reassuring findings on examination of the shunt valve. PMID- 1741224 TI - Maternal Type A behavior during pregnancy, neonatal crying, and early infant temperament: do type A women have type A babies? AB - It was hypothesized that type A behavior in pregnant women would be associated with increased neonatal crying and differential reports of infant temperament at 3 months. Type A behaviors during pregnancy were measured in a self-selected cohort of 72 healthy, primiparous, middle-class women. Their newborns were assessed at 48 hours of age and the women completed an infant temperament questionnaire at 3 months. Women who were classified as type A on the Job Involvement scale of the Jenkins Activity Survey had infants who cried more during a standardized neurobehavioral assessment compared with infants of women who were type B on the same scale. Women who were type A for Job Involvement rated their 3-month-old infants as more intense and less predictable in their responses to the environment. They were also more likely to be breast-feeding their infants at 3 months. This is the first study to examine the prevalence and nature of maternal type A behaviors during pregnancy and to show their relationship to neonatal crying behavior, to maternal report of early infant temperament, and to maternal breast-feeding. PMID- 1741225 TI - Behavior and parental expectations of child pedestrians. AB - Pedestrian injuries remain the most common cause of death from trauma for young school-age children. This study was based on the hypothesis that parents' abilities to accurately assess their children's street-crossing skills vary with the crossing test and age of the children, being less accurate for younger children. Children at three developmental levels (aged 5 through 6, 7 through 8, and 9 through 10 years) and their parents were evaluated on four street-crossing tests and a control vocabulary test. For each test, children's answers were compared to parents' estimates of their children's performance. Parents overestimated the abilities of their 5-through 6-year-olds on all four tests (P less than .01). Parents overestimated the abilities of 7- through 8-year-olds on two of the tests (P less than .05) and parents accurately assessed the abilities of the 9- through 10-year-olds. On the vocabulary test, parents overestimated their children's performance at all age levels (P less than .01). The results support the hypothesis and indicate that parents' expectations for their children's pedestrian skills are least accurate for 5- and 6-year-olds, with the mismatch decreasing as children get older. Inaccurate expectations of children's pedestrian skills may be fruitful target for injury prevention programs. PMID- 1741226 TI - Diagnosis-related criteria in the consideration of extracorporeal membrane oxygenation in neonates previously treated with high-frequency jet ventilation. AB - High-frequency jet ventilation (HFJV) is one of several high-frequency techniques that are particularly valuable for treating the neonate with lung disease refractory to conventional ventilation or with pulmonary air leak. Extracorporeal membrane oxygenation (ECMO) has also emerged as a valuable rescue therapy for neonates of more than 2000 g birth weight and 34 weeks' gestation with intractable respiratory failure. With the concurrent introduction of HFJV and ECMO, the authors sought to evaluate the role of HFJV prior to the institution of ECMO therapy. The data base for 2856 neonates receiving mechanical ventilation in one unit was used to identify 73 (of 298 total) neonates treated with HFJV, who were eligible by age and weight criteria for ECMO. Patients were grouped by diagnosis, and the oxygenation index (OI) was calculated during therapy. Outcome was evaluated for mortality, and the sensitivity of the OI for predicting mortality was calculated. Neonates who survived with HFJV alone presented with an OI of 0.30 +/- 0.03 (SEM), significantly less than nonsurvivors (0.42 +/- 0.04, P = .016). Survivors responded to HFJV with a rapid decrease in OI at 1 hour (0.19 +/- 0.02, P less than .001) and 6 hours (0.15 +/- 0.01, P less than .001). Nonsurvivors did not respond significantly at 1 hour (OI = 0.33 +/- 0.04, P = not significant [NS]) or at 6 hours (OI = 0.40 +/- 0.06, P = NS). By diagnosis, neonates with respiratory distress syndrome survived more often with HFJV (28/34, 82%) than neonates with meconium aspiration (10/26, 38%) or diaphragmatic hernia (3/9, 33%). Neonates with respiratory distress syndrome seldom presented with high OI values, but the majority of those who did survived (5/7 survived with initial OI greater than or equal to 0.40).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741227 TI - National Cholesterol Education Program (NCEP): highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. PMID- 1741228 TI - Cholesterol screening by primary care pediatricians: a study of attitudes and practices in the Minneapolis-St Paul metropolitan area. AB - A telephone survey of the 197 board-certified pediatricians actively engaged in primary care in the Minneapolis-St Paul metropolitan area was conducted to assess their cholesterol screening practices and hypercholesterolemia management. The response rate was 95%. Nearly all the pediatricians (90%) do some cholesterol screening, with the majority (58%) screening only children with a strong family history of coronary heart disease. Though only 33% screen all their patients, 66% advocate universal pediatric screening. Most of the pediatricians indicated they would manage hypercholesterolemia patients themselves, nearly always with dietary means. Despite their strong support for screening, the pediatricians expressed skepticism about the significance of childhood cholesterol level as a predictor of adult cardiovascular disease and doubted their effectiveness in getting patients to adopt a cholesterol-reducing diet. Their definition of elevated total cholesterol level in childhood was consistent with published recommendations, but only 29% could define elevated low-density lipoprotein cholesterol level. The pediatricians expressed strong opposition to pediatric cholesterol screening in schools or in any setting other than clinics and hospitals. PMID- 1741229 TI - Accuracy of central venous pressure measurement from the abdominal inferior vena cava. AB - Central venous pressure measurements in the abdominal inferior vena cava were compared with measurements in the right atrium in 10 infants and 10 children during cardiac catheterization. At end expiration, the mean pressures at these two sites were within 1 mm Hg of each other in all 20 patients, with a mean difference of 0.0 +/- 0.36 mm Hg. The abdominal inferior vena cava is a safe and convenient site for measurement of central venous pressure, and our study confirms that such measurements are accurate. PMID- 1741230 TI - Should children, parents, and pediatricians worry about cholesterol? PMID- 1741231 TI - American Academy of Pediatrics Committee on Sports Medicine and Fitness: Horseback riding and head injuries. PMID- 1741232 TI - American Academy of Pediatrics Committee on Psychosocial Aspects of Child and Family Health: The child as a witness. AB - 1. Children are often involved with the courts in cases of abuse and custody dispute and may be required to be witnesses. 2. Pediatricians have important roles in assisting children by providing psychosocial support for the precipitant life event and the event of subsequent appearance in court. 3. A pediatrician also may be able to contribute to a child's adaptation by advocating for accommodations in the legal process that are in the child's best interest. PMID- 1741233 TI - American Academy of Pediatrics Committee on Psychosocial Aspects of Child and Family Health: The pediatrician and childhood bereavement. PMID- 1741234 TI - Role of the pediatrician in the multidisciplinary team. PMID- 1741235 TI - Little League baseball and head injury. PMID- 1741236 TI - Infirmary-style sick child day care. PMID- 1741237 TI - Disposable diapers vs the environment. PMID- 1741238 TI - Definition of bronchopulmonary dysplasia. PMID- 1741239 TI - Do pediatricians like childish ads? PMID- 1741240 TI - Pharmaceutical and Biomedical Analysis Meeting. Leiden, The Netherlands, 22, November 1991. Abstracts. PMID- 1741241 TI - Enzyme inhibition in Cardiovascular disease, Weesp, The Netherlands, 13 December 1991. Abstracts. PMID- 1741242 TI - Impairment: "It's not just drugs". PMID- 1741243 TI - HIV and tuberculosis: implications for NJ nurses. PMID- 1741244 TI - Purification and biochemical characterisation of the EcoR124 type I modification methylase. AB - Large scale purification of the type I modification methylase EcoR124 has been achieved from an over-expressing strain by a two step procedure using ion exchange and heparin chromatography. Pure methylase is obtained at a yield of 30 mg per gm of cell paste. Measurements of the molecular weight and subunit stoichiometry show that the enzyme is a trimeric complex of 162 kDa consisting of two subunits of HsdM (58 kDa) and one subunit of HsdS (46 kDa). The purified enzyme can methylate a DNA fragment bearing its cognate recognition sequence. Binding of the methylase to synthetic DNA fragments containing either the EcoR124 recognition sequence GAAN6RTCG, or the recognition sequence GAAN7RTCG of the related enzyme EcoR124/3, was followed by fluorescence competition assays and by gel retardation analysis. The results show that the methylase binds to its correct sequence with an affinity of the order 10(8) M-1 forming a 1:1 complex with the DNA. The affinity for the incorrect sequence, differing by an additional base pair in the non-specific spacer, is almost two orders of magnitude lower. PMID- 1741245 TI - Cooperative binding of the globular domains of histones H1 and H5 to DNA. AB - In view of the likely role of H1-H1 interactions in the stabilization of chromatin higher order structure, we have asked whether interactions can occur between the globular domains of the histone molecules. We have studied the properties of the isolated globular domains of H1 and the variant H5 (GH1 and GH5) and we have shown (by sedimentation analysis, electron microscopy, chemical cross-linking and nucleoprotein gel electrophoresis) that although GH1 shows no, and GH5 little if any, tendency to self-associate in dilute solution, they bind highly cooperatively to DNA. The resulting complexes appear to contain essentially continuous arrays of globular domains bridging 'tramlines' of DNA, similar to those formed with intact H1, presumably reflecting the ability of the globular domain to bind more than one DNA segment, as it is likely to do in the nucleosome. Additional (thicker) complexes are also formed with GH5, probably resulting from association of the primary complexes, possibly with binding of additional GH5. The highly cooperative nature of the binding, in close apposition, of GH1 and GH5 to DNA is fully compatible with the involvement of interactions between the globular domains of H1 and its variants in chromatin folding. PMID- 1741246 TI - Slippage synthesis of simple sequence DNA. AB - The analysis of slippage synthesis of simple sequence DNA in vitro sheds some light on the question of how simple sequences arise in vivo. We show that it is possible to synthesize all types of repetitious di- and trinucleotide motifs starting from short primers and a polymerase in vitro. The rate of this synthesis depends on a sequence specific slippage rate, but is independent of the length of the fragments being synthesized. This indicates that only the ends of the DNA fragments are involved in determining this rate and that slippage is accordingly a short range effect. Slippage synthesis occurs also on a fixed template where only one strand is free to move, a situation which resembles chromosome replication in vivo. It seems therefore likely that slippage during replication is the cause of the observed length polymorphism of simple sequence stretches between individuals of a population. PMID- 1741247 TI - Molecular and functional analysis of the XPBC/ERCC-3 promoter: transcription activity is dependent on the integrity of an Sp1-binding site. AB - The human XPBC/ERCC-3 gene, which corrects the excision-repair defect in xeroderma pigmentosum group B cells and the UV-sensitive CHO mutant 27-1 cells, appears to be expressed constitutively in various cell types and tissues. We have analysed the structure and functionality of the XPBC/ERCC-3 promoter. Transcription of the XPBC/ERCC-3 gene is initiated from heterogeneous sites, with a major startpoint mapped at position -54 (relative to the translation start codon ATG). The promoter region does not possess classical TATA and CAAT elements, but it is GC-rich and contains three putative Sp1-binding sites. In addition, there are two elements related to the cyclic AMP (cAMP)-response element (CRE) and the 12-O-tetradecanoyl phorbol-13-acetate-response element (TRE) in the 5'-flanking region. Transient expression analysis of XPBC/ERCC-3 promoter-CAT chimeric plasmids revealed that a 127-bp fragment, spanning position -129 to -3, is minimally required for the promoter activity. Transcription of the XPBC/ERCC-3 promoter depends on the integrity of a putative Sp1-binding site in close proximity to the major cap site. Band shift assays showed that this putative Sp1-binding site can interact specifically with a nuclear factor, most likely transcription factor Sp1 (or an Sp1-like factor) in vitro. PMID- 1741248 TI - The human insulin gene linked polymorphic region exhibits an altered DNA structure. AB - Regulation of transcription of the human insulin gene appears to involve a series of DNA sequences in the 5' region. Hypersensitivity to DNA structural probes has previously been demonstrated in regulatory regions of cloned genomic DNA fragments, and been correlated with gene activity. To investigate the structure of the DNA in the human insulin gene, bromoacetaldehyde and S1 nuclease were reacted with a supercoiled plasmid containing a 5kb genomic insulin fragment. Both probes revealed the human insulin gene linked polymorphic region (ILPR), a region (-363) upstream of the transcriptional start site which contains multiple repeats of a 14-15mer oligonucleotide with the consensus sequence ACAGGGGT(G/C)(T/C)GGGG, as the major hypersensitive site. Fine mapping and electron microscopic analysis both show a very different behaviour of the two DNA strands in the region of the ILPR and suggest the G-rich strand may be adopting a highly structured conformation with the complementary strand remaining largely single stranded. PMID- 1741249 TI - The LCR-like alpha-globin positive regulatory element functions as an enhancer in transiently transfected cells during erythroid differentiation. AB - A positive regulatory element (PRE) similar to the locus control region (LCR) of the human beta-globin gene cluster has recently been identified 40 kb upstream of the human zeta-globin mRNA cap site (Higgs D.R. W.G. Wood, A.P. Jarman, J. Sharpe, J. Lida, I.M. Pretorius, and H. Ayyub. 1990). We investigated the influence of the alpha PRE on human alpha-globin promoter activity in transiently transfected cells. The introduction of the alpha PRE into alpha-globin promoter/CAT expression constructs increased alpha-globin promoter activity by 15 30 fold in a human erythroid cell line (Putko) as well as in mouse erythroleukemia cells (MELCs) induced with hexamethylene bisacetamide (HMBA). When these constructs were introduced into uninduced MELCs or HeLa cells, only a 2-3 fold increase in alpha-globin promoter activity was observed. Deletion of 600 bp of alpha-globin 5' flanking sequences containing six putative SP1-binding sites had no significant effect on levels of alpha-globin promoter enhancement by the alpha PRE. We further demonstrated that the alpha PRE and HS2 of the beta-LCR could similarly enhance transcriptional activity of the SV40 early promoter in HMBA induced MELCs. Finally, we showed that alpha-globin promoter activity in the presence of the alpha PRE increased with continued HMBA exposure and was coincident with transcriptional activation of endogenous globin genes. PMID- 1741250 TI - Promoter selectivity of the stationary-phase forms of Escherichia coli RNA polymerase and conversion in vitro of the S1 form enzyme into a log-phase enzyme like form. AB - Upon growth transition of Escherichia coli cells from exponential to stationary phase, RNA polymerase is converted into at least three different forms (S1, S2 and S3), which could be separately isolated by phosphocellulose column chromatography (Ozaki et al., 1991 (2)). Here, the promoter selectivity of these three stationary-phase enzymes was examined using an in vitro mixed transcription system and an E. coli promoter collection. These altered forms of RNA polymerase showed different recognition properties of promoters from that by the log-phase holoenzyme (L1). One of the stationary-phase RNA polymerases, S1, was found to be converted in vitro into an enzyme like the log-phase form following incubation with nucleotides or pyrophosphate. The conversion was indicated by not only the shift of elution position from a phosphocellulose column but also the change in the promoter selectivity. These results may suggest that RNA polymerase is interconvertible between different forms with different promoter selectivity by interaction with a phosphorylated compound(s). PMID- 1741251 TI - S1 nuclease hypersensitive sites in an oligopurine/oligopyrimidine DNA from the t(10;14) breakpoint cluster region. AB - Recurring chromosomal translocations are frequently seen in cancers, especially in leukemias and lymphomas. The genes affected by these chromosomal translocations appear to play an important role in oncogenesis. The mechanism underlying the formation of chromosomal translocation is a subject under extensive study. In chromosomal translocations involving the Ig and TCR loci, complete heptamer-spacer-nonamer signal motifs are usually present at the break of the Ig and TCR genes, indicating the involvement of V-D-J recombinase(s). On the other hand, in only about 50% of the cases signal motif sequences have been found at the break in the other participating chromosome, suggesting that different mechanisms may be involved in the scission of the corresponding chromosome. Here we report the identification of an oligopurine/oligopyrimidine DNA in the t(10;14) breakpoint cluster region associated with T-cell acute lymphoblastic leukemia. S1 nuclease mapping revealed multiple S1 hypersensitive sites in the oligopurine/oligopyrimidine DNA. These data suggest a role for oligopurine/oligopyrimidine sequences (non-B DNA) in the formation of chromosomal translocation. PMID- 1741252 TI - Biophysical analysis of DNA modified by 1,2-diaminocyclohexane platinum(II) complexes. AB - Modification of DNA and double-stranded deoxyoligonucleotides with antitumour 1,2 diamino-cyclohexanedinitroplatinum(II) (Pt-dach) complexes was investigated with the aid of physico-chemical methods and chemical probes of nucleic acid conformation. The three Pt-dach complexes were used which differed in isomeric forms of the dach nonleaving ligand-Pt(1R,2R-dach), Pt(1S,2S-dach) and Pt(1R,2S dach) complexes. The latter complex has lower antitumour activity than the other two Pt-dach complexes. Pt(1R,2S-dach) complex exhibits the slowest kinetics of its binding to DNA and of the conversion of monofunctional binding to bifunctional lesions. The anomalously slow electrophoretic mobility of multimers of the platinated and ligated oligomers suggests that bifunctional binding of Pt dach complexes to a d(GG) site within double-stranded oligonucleotides induces bending of the oligomer. In addition, chemical probing of double-helical deoxyoligonucleotides modified by the Pt-dach complexes at the d(GG) sites reveals that Pt(1R,2S-dach) complex induces more extensive conformational changes in the oligomer than Pt(1R,2R-dach) and Pt(1S,2S-dach) complexes. It is proposed that different effects of the Pt-dach complexes on DNA observed in this work arise mainly from a steric crowding of the axially oriented cyclohexane ring in the DNA adduct of Pt(1R,2S-dach) complex. PMID- 1741253 TI - In vitro definition of the yeast RNA polymerase I promoter. AB - The structure of the ribosomal gene promoter from Saccharomyces cerevisiae has been analyzed in a whole cell in vitro extract. The promoter contains at least two essential domains, an upstream domain located at the 5' boundary near position -150 and a core promoter domain around the site of transcription initiation at +1. The upstream domain augments transcription in vitro but is not absolutely required. Maintenance of correct spacing between the two domains is critical. The in vitro analysis agrees well with prior in vivo analysis and it appears that the yeast promoter has a structure very similar to that of vertebrate ribosomal gene promoters. PMID- 1741254 TI - Identification of USF as the ubiquitous murine factor that binds to and stimulates transcription from the immunoglobulin lambda 2-chain promoter. AB - To study the specificity and identity of NF-lambda 2, a ubiquitous murine nuclear factor that interacts specifically with the promoter of the lambda 2-chain gene and stimulates its transcription, competition experiments were carried out using DNA fragments from various immunoglobulin regulatory elements. The results showed that a fragment containing the H-chain enhancer competed efficiently for the binding of NF-lambda 2. Dissection of the H-chain enhancer revealed that the microE3 motif contributed the competing ability. Additionally, a regulatory region found in the adenovirus major late promoter, which interacts with the human general transcription factor USF, competed very efficiently for binding to NF-lambda 2. This region contains a sequence, CACGTGAC, which is identical to a region within the NF-lambda 2 motif. The pattern of complexes formation using oligonucleotide probes corresponding to the NF-lambda 2 and USF motifs were identical, and they both differed from that displayed by the E3 probes. Antisera against different domains of USF also react specifically with NF-lambda 2 showing that this factor is antigenically related, if not identical, to USF. Furthermore, the activity of the lambda 2 promoter in an in vitro transcription assay was significantly reduced when the nuclear extract used was USF-depleted. Addition of exogenous USF to this extract restored the transcription activity. Therefore, we conclude that NF-lambda 2 is the murine homologue of USF. PMID- 1741255 TI - A new rRNA processing mutant of Saccharomyces cerevisiae. AB - We have identified from a collection of temperature sensitive yeast mutants strains which fail to process rRNA normally. Characterization of one such mutant is reported here. This strain accumulates increased amounts of the 35S primary transcript, '24S' molecules extending from the transcription start site to the 5.8S region, and two classes of 5.8S rRNA with 5' extensions of 7 and 149 bases, respectively. We show that this pleiotropic change in the rRNA processing pattern is due to a single mutation. Possible models for the function of the mutated gene are discussed. PMID- 1741256 TI - In vivo stability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides. AB - Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO 1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbed into circulation from the peritoneal cavity. All tissues examined except brain accumulated the compound reaching concentrations calculated to be in the micromolar range. TFO-1 was found to be stable in circulation and in tissues in that a large fraction of intact material was detected 8 hours after injection, as assessed by gel electrophoresis. Approximately 20-30% of the injected dose was excreted in the urine over an 8 hour period. These results suggest that G-rich oligonucleotides, minimally modified at the 3' end, are relatively stable in vivo and have distribution kinetics favorable to use as therapeutic agents. PMID- 1741257 TI - Poly(rA) binds poly(rG).poly(rC) to form a triple helix. AB - Poly(rA) binds poly(rG).poly(rC) to form a triple helix. Evidence for this structure includes ultraviolet absorbance mixing curves and melting curves, and circular dichroism spectroscopy. The formation of the triple helix depends on the length of the poly(rC) strand. Triple helix forms when the average length is around 100 nucleotides but does not form when the average length is about 500 nucleotides. PMID- 1741258 TI - Autonomous activity of the alternate aldolase A muscle promoter is maintained by a sequestering mechanism. AB - The mouse aldolase A gene contains two closely-spaced alternate promoter/first exons. The more distal of the two, the M promoter, is muscle-specific while the 3' promoter, the H promoter, is expressed constitutively. Various segments from these promoter regions were linked to a reporter gene and used to transfect the myogenic cell line C2C12 and the hepatoma cell line BWTG3. A muscle-specific enhancer, MEN1, responsible for 80% of promoter M activity and containing 4 consensus MyoD binding sites was localized between -2578 to -2723 of the M promoter. Another muscle-specific enhancer and a restrictive element, MEN2/MSE, were found in the interval -1100 to -350. The MSE restrictive element was found to prohibit inappropriate up-regulation of the M promoter by selectively sequestering it from H promoter elements in both myoblasts and myotubes. Among the H promoter elements was found an enhancer, HEN, situated between -533 and 200 which did not function in myotubes. These studies also show that H promoter elements can act synergistically with a non-specific element, MAE, located between -350 and -130 of the M cap site greatly stimulating M promoter transcription in all cell types when the MSE restrictive element was absent. Through the analysis of interactions between these elements and the aldolase A and HSV-TK promoters we showed that neither the enhancers nor the promoter proximal sequences by themselves contain adequate information to reproduce the native pattern of aldolase A promoter modulation. Rather, the sequestering of the M promoter by the MSE restrictive element and the relative positioning and context of promoters M and H appear critical to the regulated expression of aldolase A. PMID- 1741259 TI - The NH2-terminal arms of trp repressor participate in repressor/operator association. AB - The 3-dimensional structure of the trp repressor, aporepressor, and repressor/operator complex have been described. The NH2-terminal arms of the protein, comprising approximately 12-14 residues, were not well resolved in any of these structures. Previous studies by Carey showed that the arms are required for full in vitro repressor activity. To examine the roles of the arms more fully we have removed codons 2-5 and 2-8 of the trpR gene and analyzed the resulting truncated repressors in vivo and in vitro. The delta 2-5 trp repressor was found to be approximately 25% as active as the wild type repressor in vivo. In in vitro equilibrium binding experiments, the delta 2-5 trp repressor was shown to be five fold less active in operator binding. The rate of dissociation of the complex formed between the delta 2-5 trp repressor and operator was essentially the same as the rate of dissociation of the wild type trp repressor/operator complex. However association of the delta 2-5 trp repressor with operator was clearly defective. Since the NH2-terminal arms of the trp repressor appear to affect association predominantly they may play a role in facilitating non-specific association of repressor with DNA as repressor seeks its cognate operators. The delta 2-8 trp repressor was unstable in vivo and in vitro, suggesting that some portion of the NH2-terminal arm is required for proper folding of the remainder of the molecule. PMID- 1741260 TI - Structure and mapping of the fosB gene. FosB downregulates the activity of the fosB promoter. AB - We have determined the genomic structure of the fosB gene and shown that it consists of 4 exons and 3 introns at positions also found in the c-fos gene. By deletion analysis we have characterized a region upstream of the TATA box which is the promoter region of the gene. Several consensus sequences have been identified, including an SRE and AP-1 binding site whose relative positions are identical to those in the 5' upstream region of the c-fos gene. We have also shown that FosB and c-Fos can downregulate the activity of the fosB promoter to a similar extent. The fosB gene is located in the [A1-B1] region of mouse chromosome 7. PMID- 1741261 TI - A conserved region in the sea urchin U1 snRNA promoter interacts with a developmentally regulated factor. AB - The expression of the sea urchin L. variegatus U1 snRNA gene is temporally regulated during embryogenesis. Using a microinjection assay we show that a region between 203 and 345 nts 5' of the gene is required for expression. There are four conserved regions between two sea urchin species in the 345 nts 5' to the U1 gene. One region, located at about -300, binds a protein factor which is present in blastula but not gastrula nuclei. Three other potential protein binding sites within the first 200 nts 5' to the gene have been identified using a mobility shift assay and/or DNase I footprinting. Two of these regions bind factors which are not developmentally regulated and one binds a factor which is developmentally regulated. It is likely that the factor which binds at -300 is involved in expression and developmental regulation of the sea urchin U1 snRNA gene. PMID- 1741262 TI - Isolation and identification of restriction endonuclease Aor51HI from Acidiphilium organovorum 51H. PMID- 1741263 TI - Identification of the radC102 mutation. Order of the genes in the 81.5-82.0 min region of the Escherichia coli chromosome. PMID- 1741265 TI - Sequence and genomic locus of a Leishmania protein homologous to rat ribosomal protein S8. PMID- 1741264 TI - Molecular cloning of the chicken SCL cDNA. PMID- 1741266 TI - Characterization of the cDNA sequences of two Xenopus ets-2 proto-oncogenes. PMID- 1741267 TI - Nucleotide and deduced amino acid sequence of the recA gene of Vibrio cholerae. PMID- 1741268 TI - cDNA nucleotide sequence of Sn, a regulatory gene in maize. PMID- 1741269 TI - Nucleotide sequence of the sheep MyoD1 gene. PMID- 1741270 TI - Nucleotide sequence of the POL3 gene encoding DNA polymerase III (delta) of Saccharomyces cerevisiae. PMID- 1741271 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1741272 TI - DNA containing a chemically reduced apurinic site is a high affinity ligand for the E. coli formamidopyrimidine-DNA glycosylase. AB - The E. coli Formamidopyrimidine-DNA Glycosylase (FPG protein), a monomeric DNA repair enzyme of 30.2 kDa, was purified to homogeneity in large quantities. The FPG protein excises imidazole ring-opened purines and 8-hydroxyguanine residues from DNA. Besides DNA glycosylase activity, the FPG protein is endowed with an EDTA-resistant activity which nicks DNA at apurinic/apyrimidic sites (AP sites). In contrast, DNAs containing chemically reduced AP sites are not incised by the FPG protein. However, the DNA glycosylase activity of the FPG protein is strongly inhibited in the presence of a purified synthetic 24 base-pair double-stranded oligonucleotide which contains a single apurinic site transformed chemically through borohydride reduction into a ring-opened deoxyribose derivative. The ability of the FPG protein to form a complex with this synthetically modified DNA was studied by electrophoresis in non-denaturing polyacrylamide gels. The FPG protein specifically binds the double-stranded oligonucleotide containing an apurinic site previously reduced in the presence of sodium borohydride. The complex was identified as a single retardation band on non-denaturing polyacrylamide gel electrophoresis. Complex formation is reversible and an apparent dissociation constant, KDapp, of 2.6 x 10(-10) M was determined. In contrast, no such retardation band was obtained between the FPG protein and double-stranded DNA containing an intact apurinic site or single-stranded DNA containing either an intact or a reduced apurinic site. PMID- 1741273 TI - Copy number control of the streptococcal plasmid pIP501 occurs at three levels. AB - Transcriptional analysis of the replication region of plasmid pIP501 has revealed three active promoters. The repR gene which is essential for pIP501 replication was transcribed from promoter pII. A small antisense RNA (136 nt, RNAIII) generated from promoter pIII was complementary to the leader region of the repR mRNA. Introduction of either point mutations or deletions into promoter pIII or RNAIII resulted in a 5-20fold increased plasmid copy number suggesting a negative regulatory function for RNAIII. The copR gene, the complete DNA and amino acid sequence of which is reported, was dispensable for pIP501 replication. However, deletion of the copR promoter pI and/or the copR coding sequence led to a 10 20fold increase in plasmid copy number. This effect was also observed when a -1 frameshift mutation was introduced into the CopR coding region. Mutations in copR and pIII/RNAIII were not additive. It is, therefore, proposed that both components act at the same level of copy number control most likely in a sequential way. A second level of copy number control was found to involve an inverted repeat structure upstream of and overlapping with promoter pII. Destruction of this repeat sequence by deletion caused an increase in copy number 2-3fold higher than that observed for either RNAIII or copR mutations. A working model is proposed how different components of pIP501 interact to regulate its copy number. PMID- 1741274 TI - Binding of a nuclear protein to the rat growth hormone silencer element. AB - The rat growth hormone (rGH) gene is uniquely expressed in a subset of cells from the anterior pituitary. This strongly cell type specific expression is controlled by both cis-acting positive sequences that bind the pituitary specific transcription factor Pit-1 and cis-acting negative regulatory elements that lie upstream of the Pit-1 sites. The negative elements act to prevent expression of the gene in inappropriate cell types. Here we report that the most proximal rGH silencer element is specifically bound by a protein found in a number of rGH non expressing cell types and which exerts a negative regulatory effect through the recognition of this rGH element in transient transfection assays. The sequence recognized by this protein is similar to sequences of several other negative regulatory elements as well as to the consensus binding site for the transcription factor NF1. However, the 45 KDa molecular weight identified for this protein does not correspond to any of the sizes previously reported for NF1 suggesting that it is likely to represent a new member amongst this family of transcription factors. PMID- 1741275 TI - The role of a minor groove spine of hydration in stabilizing poly(dA).poly(dT) against fluctuational interbase H-bond disruption in the premelting temperature regime. AB - Experimental estimates of the premelting Adenine-Thymine base pair opening probability for some B-DNA sequences are two orders of magnitude smaller than those of other B-DNA sequences. The AT pairs in the sequence with smaller open probability seem to be those that have a well defined spine of hydration in the minor groove. We show that this spine of hydration can significantly enhance the thermal stability of the base pairs to which they are attached. The effect of this spine of hydration coupled with the possible stabilization effect contributed from neighboring GC pairs can explain the differences in the observed AT pair opening probability for different AT containing B-DNA sequences. PMID- 1741276 TI - Purification and properties of the MboII, a class-IIS restriction endonuclease. AB - After five purification steps a homogeneous preparation of endonuclease MboII was obtained, and several properties of the enzyme were determined. MboII is a monomer, with Mr under native and denaturing conditions being 47-49 x 10(3) Da. Endonuclease MboII is a basic protein (pI 8.3) which remains active when Mg2+ is replaced by Mn2+, Co2+, Ca2+, or Fe2+. MboII exhibits a star activity in the presence of some of the following reagents or ions: DMSO, glycerol, ethanol (and Co2+ or Mn2+ at pH 6). MboII does not bend DNA and is heat sensitive, losing activity after 15 min at 50 degrees C. PMID- 1741277 TI - The long repetitive polypurine/polypyrimidine sequence (TTCCC)48 forms DNA triplex with PU-PU-PY base triplets in vivo. AB - Polypurine/polypyrimidine repetitive sequences occur with high frequency in eucaryotic genomes, particularly around transcription units. Since such sequences are known to adopt triple stranded-structures under appropriate conditions in vitro, it is of major interest to know if they occur in vivo, and thus if they can have some biological importance by inducing structural constraints in the genomic DNA. To this end, we have isolated a (TTCCC)48 sequence, present in the promoter of an avian gene, and tested its ability to form PU-PY-PY and PU-PU-PY triple helices in vitro, through the oligonucleotide gel shift technique and single strand-specific nuclease footprinting. We have then developed an oligonucleotide protection assay, which can be adapted to in vivo investigations. This strategy leads us to conclude that in vivo conditions allow preponderant formation of triplex of the PU-PU-PY class. PMID- 1741278 TI - Imaging and nanodissection of individual supercoiled plasmids by atomic force microscopy. AB - The atomic force microscope (AFM) was used to image supercoiled plasmid DNA deposited on a mica surface in either a hydrated or desiccated state. Hydrated plasmid was precisely cut by the scanning tip at a location determined by the instrument operator. Small pieces of DNA (100-150 nm in length) were excised and deposited adjacent to the dissected plasmid, demonstrating that it is possible to remove and manipulate genomic DNA fragments, unresolvable by light microscopy, from defined chromosomal locations by AFM. PMID- 1741279 TI - The MRE4 gene encodes a novel protein kinase homologue required for meiotic recombination in Saccharomyces cerevisiae. AB - The MRE4 gene was cloned by complementation of the defects of meiotic recombination and haploidization in an mre4-1 mutant. Disruption of MRE4 resulted in reduced meiotic recombination and spore inviability. The mre4 spore lethality can be suppressed by spo13, a mutation that causes cells to bypass the reductional division. Analysis of meiotic DNA extracted from the mre4 mutant cells revealed that double-strand breaks occurred at the two sites of the HIS4 LEU2 recombination hot spot, but at a frequency of about 10-20% of the wild type. Northern blot analysis indicated that the MRE4 gene produces four transcripts of 1.63, 3.2, 4.0 and 6.2 kb. All of these transcripts are absent from mitotic cells and are meiotically induced. The DNA sequence of the MRE4 open reading frame predicts a 497-amino acids protein with a molecular mass of 56.8 kDa. The Mre4 protein contains highly conserved amino acid sequences found specifically in serine-threonine protein kinases. These results suggest that protein phosphorylation is required directly or indirectly for meiotic recombination. PMID- 1741280 TI - Molecular structures of two new anti-HIV nucleoside analogs: 9-(2,3-dideoxy-2 fluoro-beta-D-threo-pentofuranosyl)adenine and 9-(2,3-dideoxy-2-fluoro-beta-D threo-pentofuranosyl)hypoxanthine. AB - The x-ray crystal structures of two new anti-HIV compounds, 9-(2,3-dideoxy-2 fluoro-beta-D-threo-pentofuranosyl)adenine (2'-F-dd-araA) and 9-(2,3-dideoxy-2 fluoro-beta-D-threo- pentofuranosyl)hypoxanthine (2'-F-dd-aral), have been determined at two temperatures. Both crystals are in the space group P2(1)2(1)2(1), and their structures were solved by direct methods. Least-squares refinement produced final R-factors of 0.027 for the 2'-F-dd-araA structure and of 0.044 for the 2'-F-dd-aral structure, respectively. The latter structure contains a two-fold disordered conformation of the sugar moiety. All three conformers (one for 2'-F-dd-araA and two for 2'-F-dd-aral) adopt an anti chi CN glycosyl torsion angle. The sugar in the 2'-F-dd-araA structure has a C2'-endo pucker conformation, whereas the sugar in the 2'-F-dd-aral structure has a mixture of C2'-endo and C3'-endo pucker conformations. When the sugar adopts the C2'-endo conformation, the torsion angle about the C4'-C5' bond is in a transgauche+ conformation. In contrast, when the sugar adopts the C3'-endo conformation, the torsion angle about the C4'-C5' bond is in a gauche(+)-gauche- conformation. The C2'-F bond distance is 1.406(3) A, similar to that found in other aliphatic C-F bonds. The results suggest that the 2'-fluoro-2',3' dideoxyarabinosyl nucleosides do not have a strong preference for either C2'-endo or C3'-endo sugar pucker. PMID- 1741281 TI - Recognition nucleotides for human phenylalanyl-tRNA synthetase. AB - The specificity of the interaction between tRNAPhe and phenylalanyl-tRNA synthetase isolated from human placenta was investigated. Using yeast tRNAPhe transcripts with different point mutations it was shown that all the five recognition points for the yeast phenylalanyl-tRNA synthetase (G20, G34, A35, A36 and A73) are also important for the reaction catalyzed by the human enzyme. A set of mutations in nucleotides involved in tertiary interactions of tRNAPhe revealed that mutations which maintained the proper folding of the molecule had almost no influence on the efficiency of aminoacylation. The most striking difference between the yeast and human phenylalanyl-tRNA synthetases involved a mutation in the lower two base pairs of the anticodon stem. This mutation did not affect aminoacylation with the yeast enzyme, but greatly reduced activity with human phenylalanyl-tRNA synthetase. PMID- 1741282 TI - Human and human-yeast chimeric U6 snRNA genes identify structural elements required for expression in yeast. AB - U6 is the most highly conserved spliceosomal snRNA. Previous mutational studies have shown that the majority of essential residues in U6 are located in a region of 35 nucleotides encompassing a conserved hexanucleotide and stem I and stem II of the U4-interaction domain. Although the yeast and human U6 RNAs are 80% identical in this region, the human U6 gene cannot functionally replace the yeast gene in vivo. The human gene is not transcribed when placed in the context of yeast flanking sequences. Transcription of the human gene, but not its function, can be stimulated by the introduction of an A block promoter element in the U6 coding region. Using a set of human-yeast chimeras, we show that the 5' domain and the 3' terminal region of the human U6 gene can each functionally replace the corresponding yeast domains. However, a combination of both domains in a single molecule is lethal. The basis of the inability of the human U6 snRNA to function in yeast cells is discussed. PMID- 1741283 TI - Fusion of a free left Alu monomer and a free right Alu monomer at the origin of the Alu family in the primate genomes. AB - In the primate genome, a typical Alu element corresponds to a dimeric structure composed of two different but related monomeric sequences arranged in tandem. However, the analysis of primate sequences found in GenBank reveals the presence of free left and free right Alu elements. Here, we report the statistical study of those monomeric elements. We found that only a small fraction of them results from a deletion of a dimeric Alu sequence. The majority derives from the amplification of monomeric progenitor sequences and constitutes two families of monomeric elements: a family of free left Alu monomers that is composed of two subfamilies and a small family of free right Alu monomers. Both families predated the dimeric Alu elements, and a phylogenetic analysis strongly suggests that the first progenitor of the dimeric Alu family arose through the fusion of a free left monomer with a free right monomer. PMID- 1741284 TI - Highly efficient generation of recombinant baculoviruses by enzymatically medicated site-specific in vitro recombination. AB - We have used the Cre-lox system of bacteriophage P1 to develop a highly efficient in vitrosystem for construction of recombinant baculoviruses. A positive visual selection has been included to make identification of recombinant viral progeny rapid and straightforward. We report recombination frequencies as high as 5 x 10(7) recombinants/micrograms starting plasmid DNA and under certain conditions, up to 50% of the viral progeny are recombinants. Genes inserted into the baculovirus genome can be readily recovered in a simple one step process and re inserted after manipulation if required. We have confirmed the structure of recovered plasmids by diagnostic restriction endonuclease digestion and the structure of recombinant viral genomes by Southern analysis. Possible uses and the significance of the system are discussed and experiments currently being done to improve it are described. PMID- 1741285 TI - Formation of novel hairpin structures by telomeric C-strand oligonucleotides. AB - Telomeres are specialized structures at the ends of chromosomes that are required for long term chromosome stability and replication of the chromosomal terminus. Telomeric DNA consists of simple repetitive sequences with one strand G-rich relative to the other, C-rich, strand. Evolutionary conservation of this feature of telomeric repeat sequences suggests that they have specific structural characteristics involved in telomere function. Absorbance thermal denaturation, chemical modification and non-denaturing gel electrophoretic analyses showed that telomeric C-strand oligonucleotides form stable non-Watson-Crick hairpin structures containing C.C+ base pairs. Formation of such hairpins may facilitate previously reported G-strand exclusive interactions. PMID- 1741286 TI - Strand specific PCR amplification of low copy number DNA. AB - A method for the amplification of a single DNA strand at low copy number is described. It is a wholly PCR based approach which involves an initial linear amplification of the target using a tagged strand specific primer. This is followed by classical PCR amplification of the progeny using a pair of primers, one specific for the sequence tagged onto the 5' end of the first round primer, the second specific for the target sequence. Given the protocol used the ratio of the two strands in the final amplification product was 50:1. PMID- 1741287 TI - Effective incorporation of 2'-O-methyl-oligoribonucleotides into liposomes and enhanced cell association through modification with thiocholesterol. AB - Cholesterol was linked to 2'-O-methyl-oligoribonucleotides (2'-OMe-RNA) via a disulfide bond by reacting the 3'-(pyridyldithio)-modified 2'-OMe-RNA with thiocholesterol in dichloromethane-methanol solution. This ligation reaction was made possible by a novel strategy in which the highly charged oligonucleotide was rendered soluble in nonaqueous solvent through conversion to a lipophilic amidinium salt. The biodegradable lipophilic modification of 2'-OMe-RNA resulted in a large increase in incorporation of such oligonucleotides into liposomes prepared by reversephase evaporation. Furthermore, association of these modified oligonucleotides with cultured TIB 73 cells was 100-fold higher than that seen with unmodified 2'-OMe-RNA in serum-free medium and about 10 to 30-fold higher in the presence of 10% calf serum. During incubation with cells, release of the internalized oligonucleotide from the thiocholesteryl moiety can be demonstrated. PMID- 1741289 TI - Enrichment of oligonucleotide sets with transcription control signals. II: Mammalian DNA. AB - We studied the frequency distribution of oligonucleotides 10 bp long in a sample of 1.6 Mb of mammalian genes, containing 579 sequences from GenBank(R) 55.0, with the aim of detecting transcription control signals. 2216 decamers had a frequency higher than 10 times the mean and were subjected to further statistical analysis. For each of the 2216 decamers (parents), we counted the individual frequencies of the 30 decamers differing from the parent by one base mutation (progeny) and then calculated two variance/mean chi squares for the progeny, with and without the parent. We then studied the distribution of the ratio between the two chi squares. Out of 2216 decamers, 346 had a chi square ratio of 1.9 or larger. In this final set, which corresponds to less than 0.033 per cent of all possible decamers, 18 were found to contain 23 eukaryotic transcription control elements 5 10 bp of length, such as Sp1 and others. Furthermore, when compared to 210 random sets containing 346 decamers, this set contains a highly significant excess of the longer signals. PMID- 1741288 TI - The MyoD family of myogenic factors is regulated by electrical activity: isolation and characterization of a mouse Myf-5 cDNA. AB - A full-length cDNA coding for a homolog of the human Myf-5 was isolated from a BC3H-1 mouse library and characterized. The clone codes for a protein of 255 amino acids that is 89%, 88% and 68% identical to the human, bovine and Xenopus myf-5, respectively. The mouse Myf-5 cDNA (mmyf-5), as well as sequences coding for MyoD, myogenin and Mrf-4, were used to probe Northern blots to analyze the effects of innervation on the expression of the MyoD family of myogenic factors. Mouse myf-5, MyoD and myogenin mRNAs levels were found to decline in hind limb muscles of mice between embryonic day 15 (E15) and the first postnatal week, a period that coincides with innervation. In contrast, Mrf-4 transcripts increase during this period and reach steady-state levels by 1-week after birth. To distinguish if the changes in myogenic factor expression are due to a developmental program or to innervation, mRNA levels were analyzed at different times after muscle denervation. Mmyf-5 transcripts begin to accumulate 2 days postdenervation; after 1 week levels are 7-fold higher than in innervated muscle. Mrf-4, MyoD and myogenin transcripts begin to accumulate as soon as 8h after denervation, and attain levels that are 8-, 15- and 40-fold higher than found in innervated skeletal muscle, respectively. The accumulation of these three mRNAs precedes the increase of nicotinic acetylcholine receptor alpha subunit transcripts, a gene that is transcriptionally regulated by MyoD-related factors in vitro. Using extracellular electrodes to directly stimulate in situ the soleus muscle of rats, we found that 'electrical activity' per se, in absence of the nerve, represses the increases of myogenic factor mRNAs associated with denervation. PMID- 1741290 TI - Identification and functional characterization of a cis-acting positive DNA element regulating CYP 2B1/B2 gene transcription in rat liver. AB - A positive cis-acting DNA element in the near 5'-upstream region of the CYP2B1/B2 genes in rat liver was found to play an important role in the transcription of these genes. An oligonucleotide covering -69 to -98 nt mimicked the gel mobility shift pattern given by the fragment -179 to +29 nt, which was earlier found adequate to confer the regulatory features of this gene. Two major complexes were seen, of which the slower and faster moving complexes became intense under uninduced and Phenobarbitone-induced conditions respectively. Minigene cloned DNA plasmid covering -179 to +181 nt in pUC 19 and Bal 31 mutants derived from this parent were transcribed in whole nuclei and cell free transcription extracts and mutants containing only upto -75 nt of the upstream were poorly transcribed. Transcription extracts from phenobarbitone-injected rat liver nuclei were significantly more active than extracts from uninduced rats in transcribing the minigene constructs. Addition of the oligonucleotide (-69 to -98nt) specifically inhibited the transcription of the minigene construct (-179 to +181 nt) in the cell free transcription system. It is therefore, concluded that the region -69 to -98 nt acts as a positive cis-acting element in the transcription of the CYP2B1/B2 genes and in mediating the inductive effects of phenobarbitone. PMID- 1741291 TI - Chromosome translocation in Plasmodium berghei. AB - We describe a chromosome translocation in a karyotype mutant of the rodent malarial parasite Plasmodium berghei. In this mutant (named EP) a small chromosome (chromosome 7), which has exhibited a size range between 0.9 and 1.4 Mb in other clones of P. berghei, is translocated to chromosome 13 or 14 with a size of about 3 Mb. By comparison of Apa-I restriction fragments of the chromosomes from mutant EP and from a reference clone (named HP) of P. berghei, we found evidence for a junction of subtelomeric chromosome 7 sequences and internal chromosome 13/14 sequences. In addition, a new chromosome of 1.4 Mb (named EP7) is present in mutant EP, which is (mainly) composed of sequences of chromosome 13/14. EP7 contains one telomeric region derived from chromosome 13/14. We found evidence that internal sequences of chromosome 13/14 are joined to telomeric sequences in the other telomeric region of EP7. The karyotype of mutant EP was stable during asexual and sexual multiplication and we found no indications for phenotypic changes. PMID- 1741292 TI - In vitro DNA replication implicates O2-ethyldeoxythymidine in transversion mutagenesis by ethylating agents. AB - A 36-nucleotide oligomer containing a single O2-ethyldeoxythymidine (O2-Et-dT) adduct at a specific site was synthesized. The oligomer, which corresponds to a specific DNA sequence in gene G of bacteriophage phi X174, was used as a template by T7 DNA polymerase to investigate the in vitro mutagenic specificity of O2-Et dT. At 10 microM dNTP and 5 mM Mg++, the progress of T7 DNA polymerase was interrupted by O2-Et-dT: 80% 3' to O2-Et-dT and 14% after incorporating a nucleotide opposite O2-Et-dT (incorporation-dependent blocked product). DNA synthesis past the lesion was low (6%). Incorporation of a nucleotide opposite O2 Et-dT and subsequent postlesion synthesis were enhanced by increasing the dNTP concentration, with postlesion synthesis reaching 30% at 200 microM. Postlesion synthesis was further increased to 45% by addition of 10 mM dAMP to the polymerization reactions. DNA sequencing revealed that both dA and dT were incorporated opposite O2-Et-dT with dA incorporation impeding the progress of DNA synthesis. dT incorporation was efficiently extended implicating O2-Et-dT in transversion mutagenesis in vivo. These studies provide a basis for understanding the molecular mechanisms by which ethylating agents contribute to cytotoxicity, A.T transversion mutagenesis and activation of the oncogene neu by an A.T----T.A transversion event in rat neuroblastomas. PMID- 1741293 TI - Unusual DNA binding characteristics of an in vitro translation product of the CCAAT binding protein mYB-1. AB - We have isolated a cDNA that encodes the murine CCAAT-binding protein mYB-1. The deduced amino acid sequence shows 95% identity with its presumed human homologue (hYB-1A) which was originally isolated as a protein that binds to the Y box of MHC class II genes. In vitro translated mYB-1 binds to CCAAT boxes of the MHCIIE alpha, HSVTK and mouse PCNA promoters but not to alpha-globin or human thymidine kinase CCAAT boxes. Interestingly, complexes formed between the in vitro translated protein and the various CCAAT boxes display the property of being competed more efficiently with self competitor DNA, regardless of the CCAAT box initially used as a probe. A similar phenomenon was observed in a cell extract of Con-A stimulated murine splenocytes when the same competition assays were performed. These results may reflect the generation of multiple forms of a particular CCAAT-binding protein, such as mYB-1, that display distinct, yet overlapping, DNA binding specificities. PMID- 1741294 TI - Sequence of rat RL/IF-1 encoding an IkappaB, and comparison with related proteins containing notch-like repeats [corrected]. PMID- 1741295 TI - A new 3'-terminus for Xenopus laevis 28S ribosomal RNA. PMID- 1741296 TI - Nucleotide sequence of the protamine P1 gene from the whale Orcinus orca predicts a unique N-terminal amino-acid motif. PMID- 1741297 TI - Nucleotide sequence of the 5.8S ribosomal RNA gene of Lentinula edodes. PMID- 1741298 TI - A gene family of HMG-box transcription factors with homology to TCF-1. PMID- 1741299 TI - The DNA sequences of the human and hamster secretory ribonucleases determined with the polymerase chain reaction (PCR). PMID- 1741300 TI - recF in Actinobacillus pleuropneumoniae. PMID- 1741301 TI - Nucleotide sequence of the phosphoprotein (P) gene of Newcastle disease virus (strain Beaudette C). PMID- 1741302 TI - PCR cloning of a nucleotidic sequence coding for the mature part of Chlamydomonas reinhardtii thioredoxin Ch2. PMID- 1741303 TI - StsI, a new FokI isoschizomer from Streptococcus sanguis 54, cleaves 5' GGATG(N)10/14 3'. PMID- 1741304 TI - PamI and PamII restriction endonucleases from Phormidium ambiguum. PMID- 1741305 TI - High efficiency transformation of Schizosaccharomyces pombe by electroporation. PMID- 1741306 TI - Analysis of DNA curvature using circular permutation of 5' end labelled fragments. PMID- 1741307 TI - PCR amplification of long DNA fragments. PMID- 1741308 TI - Phase Lock Gel plasmid micropreps: direct insert screening, probe synthesis and sequencing within one day. PMID- 1741309 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1741310 TI - Professional development module. P5: client assessment. Part (ii): Client assessment in practice [continuing education credit]. PMID- 1741311 TI - A sobering issue. PMID- 1741312 TI - Money matters. PMID- 1741313 TI - Trusts. PMID- 1741314 TI - Trusts--how are they shaping up? PMID- 1741315 TI - Safe practices. PMID- 1741316 TI - A burning question. PMID- 1741317 TI - Profile of a profession. PMID- 1741318 TI - Running to stand still. PMID- 1741319 TI - Death with dignity. Christian Science. PMID- 1741320 TI - Wise counsel. PMID- 1741321 TI - Infection control. A risk to others. PMID- 1741322 TI - Everybody's business. PMID- 1741324 TI - High dependency nurse-patient interaction. PMID- 1741323 TI - CPNs and adults sexually abused in childhood. PMID- 1741325 TI - Opposing views on health care assistants. PMID- 1741326 TI - Friends in high places. PMID- 1741327 TI - Journal of Wound Care Nursing. Dressings for deep wounds. PMID- 1741328 TI - Journal of Wound Care Nursing. Treating Mary's foot ulcer. PMID- 1741329 TI - Journal of Wound Care Nursing. Evaluating a dressing. PMID- 1741331 TI - Moores to the point. Interview by Linda Davidson. PMID- 1741330 TI - Professional development module. P6: Facilitating learning. Part (ii): The process of facilitation. PMID- 1741332 TI - Split decisions. PMID- 1741333 TI - Women's movement? PMID- 1741334 TI - Honest PREP-aration. PMID- 1741335 TI - Smoked out. PMID- 1741336 TI - Care after death. PMID- 1741337 TI - Sexual abuse--the ultimate betrayal. PMID- 1741338 TI - Sexual abuse--treating the adult survivor. PMID- 1741339 TI - Sexual abuse--turning point. PMID- 1741340 TI - Mental health--an enviable system. PMID- 1741341 TI - Making sense of cataract surgery. PMID- 1741342 TI - Nursing narratives--dances with pigs. PMID- 1741343 TI - Nursing narratives--gentle persuasion. PMID- 1741344 TI - Nursing narratives--'them and us'. PMID- 1741345 TI - Give us a break. PMID- 1741346 TI - Death with dignity--the Mormon Church. PMID- 1741347 TI - Girls will be women. PMID- 1741348 TI - Reasons for readmission to hospital. PMID- 1741349 TI - Satisfaction with community midwifery. PMID- 1741350 TI - The quality of nursing documentation. PMID- 1741351 TI - Computing in practice. Information management & technology. Systems of care. PMID- 1741352 TI - Infection control--the hazards of communal razors. PMID- 1741353 TI - Infection control. Urine collection--in search of a fine specimen. PMID- 1741354 TI - Infection control. Urine collection--choosing the right container. PMID- 1741355 TI - More nurses doing HIV tests for insurance. PMID- 1741356 TI - Hepatitis A, B, C, D, and E. Update on testing and treatment. AB - Five major types of viral hepatitis have been identified. Hepatitis A is an acute, usually self-limited illness. Prophylaxis with immune globulin (Gamastan, Gammar) is effective in household and sexual contacts of infected patients. Hepatitis B has both acute and chronic forms. Treatment trials for chronic hepatitis B with interferon alfa-2b have shown promise. Hepatitis C is the name now given to non-A non-B hepatitis. Interferon alfa-2b (Intron A) has been approved for treatment of chronic hepatitis C. Hepatitis D occurs only in patients with hepatitis B. The only treatment for hepatitis D is prevention of hepatitis B. Hepatitis E is seen after natural disasters in developing regions of the world. Further advances in serologic testing and treatment of viral hepatitis can be expected. PMID- 1741357 TI - Hypercoagulable states. Their causes and management. AB - Recognition of patients who should be evaluated for either hereditary or acquired hypercoagulable states is important so that treatment may be instituted if necessary to prevent thrombosis. Close attention to the medical history, medications, family history, and circumstantial risk factors can help identify patients at risk so that morbidity and mortality may be reduced. Patients with hereditary thrombosis should receive lifelong anticoagulation. PMID- 1741358 TI - Diminutive polyps found on flexible sigmoidoscopy. Management and follow-up. AB - Diminutive polyps found on flexible sigmoidoscopy are predominantly hyperplastic, but it is impossible to rely on endoscopic appearance to make an accurate diagnosis. Colonoscopy, polypectomy, and full pathologic evaluation are recommended for all such polyps. Follow-up care varies depending on the nature of the lesion. PMID- 1741359 TI - Safe use of glucocorticoids. How to monitor patients taking these potent agents. AB - Glucocorticoids reduce inflammation and combat stress. However, they are very powerful, and guidelines for their use must be followed to avoid such adverse effects as Cushing's syndrome and adrenal insufficiency. Whenever possible, physicians should consider alternative treatment strategies, because the consequences of steroid therapy may be worse than those of the disease being treated. PMID- 1741360 TI - Exercise-induced bronchospasm. Achieving control in asthmatic patients. AB - Exercise-induced bronchospasm is a common complication of asthma. Aggressive treatment of this conditions permits patients to maintain full activity despite their illness. Since most asthmatic patients are healthy except for an intermittent respiratory problem, providing them the opportunity to exercise in all weather conditions affords a clear improvement in their quality of life. Conceptualizing exercise-induced bronchospasm as a hyperreactive airway response to rapid inhalation of cool, dry air leads logically to the primary methods used to treat this disorder. PMID- 1741361 TI - Postoperative pulmonary complications. When are preventive and therapeutic measures necessary? AB - Relevant clinical and physiologic data are available to help guide decision making in the management of patients who are at risk for or already have postoperative pulmonary complications. Prophylactic measures should be simple and focused. Inexpensive treatment methods should be tried before resorting to more individual-intensive and expensive measures. Proper treatment of postoperative atelectasis requires adequate patient assessment and knowledge of the therapeutic options. Costs, measured in dollars as well as in patient morbidity and mortality, are substantially greater when physicians fail to recognize and treat reversible disease before elective surgery and when effective postoperative therapy is not provided in accordance with individual needs. PMID- 1741362 TI - Coronary artery disease. The latest on prevention. AB - Because coronary artery disease is the most common cause of death in the United States, much effort is being focused on research into prevention of this killer. Dr. Lush reviews positive and negative aspects of recent trends and summarizes the results of studies on the prophylactic potential of maintenance of normal body weight, exercise, aspirin, fish oils, estrogens, and antioxidants. PMID- 1741363 TI - Can a market economy fix a broken healthcare system? PMID- 1741364 TI - A memorable lesson in orthopedics. PMID- 1741365 TI - Solutions to spiraling healthcare costs. PMID- 1741366 TI - Solutions to spiraling healthcare costs. PMID- 1741367 TI - New treatments for septic shock. PMID- 1741368 TI - Risk for renal injury in diabetic hypertensive patients. The physiologic basis for blood pressure control. AB - In determining a therapeutic approach to coexistent adult-onset (type II) diabetes and hypertension in patients who are middle-aged, special attention must be given to the pathophysiology of the hypertensive disease and how it affects the kidneys. Diabetes and hypertension potentiate renal damage, which clearly leads to a reduced life span and increased morbidity. Nonpharmacologic measures (eg, exercise, weight control, glycemic control, protein-restricted diet) and pharmacologic approaches need to be combined so as to control systemic blood pressure yet maintain adequate renal perfusion. Clearly, preexisting accentuated vascular reactivity to vasoconstrictive growth factors in diabetic patients stimulates maladaptive compensatory responses in the kidney. This precipitates greater renal injury superimposed on the relative risk of the hypertension diabetes combination itself. PMID- 1741369 TI - Risk for renal injury in diabetic hypertensive patients. Pharmacologic approaches. AB - In the first article of this pair (page 77), Drs Weir and Bakris discussed a physiologic approach to management of diabetic hypertensive patients. In this article, they discuss the latest findings regarding use of angiotensin-converting enzyme inhibitors and calcium channel blockers along with glycemic control and reduced protein intake. PMID- 1741370 TI - Cluster headache syndrome. Ways to abort or ward off attacks. AB - Cluster headache is a syndrome of severe head and facial pain accompanied by autonomic abnormalities. Men are affected more frequently than women. Headaches occur daily during periods of susceptibility, which may be followed by periods of remission. The etiology of cluster headache is uncertain. Recent work suggests that hypothalamic dysfunction and/or oxyhemoglobin desaturation may be involved in its pathogenesis. Effective medical regimens are available for aborting acute attacks and for preventing attacks. Surgical ablation of the trigeminal ganglion has been effective in some patients when conventional medical therapy has failed. PMID- 1741371 TI - Isolation and characterization of the epsilon subspecies of protein kinase C from rat brain. AB - The epsilon subspecies of protein kinase C (epsilon PKC) was purified to near homogeneity from the soluble fraction of rat brain by successive chromatographies on DEAE-cellulose, threonine-Sepharose, phenyl-5PW, Mono Q, heparin-5PW, and hydroxyapatite columns. The enzyme from COS-7 cells that were transfected with an epsilon PKC cDNA expression plasmid showed the same elution profile. The purified enzyme from the brain was a double (96 and 93 kDa) on SDS/PAGE. Both the doublet proteins were recognized by antibodies raised against several oligopeptides that were parts of the deduced amino acid sequence of the rat brain epsilon PKC. When treated with potato acid phosphatase, both doublet proteins disappeared with the concomitant appearance of a single protein at 90 kDa, suggesting that epsilon PKC exists in the tissue as phosphorylated forms. The physiological significance of this phosphorylation is unknown. The enzymes from the rat brain and COS-7 cells were indistinguishable from each other in their kinetic and catalytic properties. Unlike alpha-, beta I-, beta II-, and gamma PKC, epsilon PKC was independent of Ca2+ but absolutely required phosphatidylserine and diacylglycerol for its activation; a tumor-promoting phorbol ester could replace diacylglycerol. epsilon PKC showed enzymological properties similar to those of delta PKC, except that epsilon PKC but not delta PKC was greatly activated by free arachidonic acid. Immunoblot analysis revealed that, in marked contrast to delta PKC, epsilon PKC is expressed predominantly in the brain tissue and only in trace amounts in heart, lung, spleen, thymus, and testis. PMID- 1741372 TI - Mechanism of SOS mutagenesis of UV-irradiated DNA: mostly error-free processing of deaminated cytosine. AB - We measured the kinetics of growth and mutagenesis of UV-irradiated DNA of phages S13 and lambda that were undergoing SOS repair; the kinetics strongly suggest that most of SOS mutagenesis arises from the deamination of cytosine in cyclobutane pyrimidine dimers, producing C----T transitions. This occurs because the SOS mechanism bypasses T--T dimers promptly, while bypass of cytosine containing dimers is delayed long enough for deamination to occur. The mutations are thus primarily the product of a faithful mechanism of lesion bypass by a DNA polymerase and are not, as had been generally thought, the product of an error prone mechanism. All of these observations are explained by the A-rule, which is that adenine nucleotides are inserted noninstructionally opposite DNA lesions. PMID- 1741373 TI - Structure of clonal and polyclonal cell arrays in chimeric mouse retina. AB - One of the most striking results of recent cell-lineage studies of vertebrate retina is the marked variability in the size and types of clones marked by retroviral transfection and dye injection of embryonic progenitor cells. Is this variability due to microenvironmental modulation of cell determination, to lineage restriction, or to experimental perturbation of the progenitor cells? We have taken advantage of species-specific DNA probes to mark groups of lineage related cells in experimental mouse chimeras. This method of marking cells has two distinct advantages over previous methods: direct manipulation of progenitor cells is avoided, and clones are established at an earlier stage of retinal development. The most notable feature of retinal cohorts in chimeras is their structural uniformity--each is a solid radial array that contains the same ratio of major cell types as the retina itself. This is true even of the smallest monoclonal cohorts, which contain fewer than 200 cells. Our results provides compelling empirical support for the hypothesis that the murine retina is made up of hundreds of relatively homogeneous radial units, each derived from single retinal precursor cells. This finding is inconsistent with micro-environmental modulation of clone structure early in development. We raise the possibility that the heterogeneity among clones marked by dye injection and transfection is due to progressive lineage restriction or to experimental perturbation of the retinal progenitor cells. PMID- 1741374 TI - The lethal(1)optomotor-blind gene of Drosophila melanogaster is a major organizer of optic lobe development: isolation and characterization of the gene. AB - The X-chromosomal complementation unit lethal(1)optomotor-blind [l(1)omb] is defined by lack of complementation among over a dozen recessive lethal mutations that map to the omb gene locus. Mutations in l(1)omb also fail to complement viable mutations of three seemingly unrelated functions in this region: bifid (bi), manifesting defective wings, Quadroon (Qd), a semi-dominant mutation expressing abnormal tergite pigmentation, and In(1)ombH31, giving rise to a normal external morphology but with discrete defects in the optic lobes and behavior. The locus encodes a 70-kilobase primary transcript that is spliced into a 6-kilobase mature RNA. cDNAs for this transcript were isolated and sequenced and the derived amino acid sequence was analyzed. Certain features of this sequence suggest that the l(1)omb gene product is a nuclear regulatory protein. The lethal phase of various apparent null mutants was determined and found to occur mainly in the pupal stage. A large proportion of all hemizygous mutant males develop to pharate adults that eclose only rarely but can be rescued from the pupal case. These animals show a severe maldevelopment of the optic lobes. In addition they have only rudimentary wings as well as a Quadroon-like abdominal pigmentation. Thus, in the lethal mutants those parts of the body are affected for which independent viable mutations have been previously described in the omb locus, such as optomotor-blind, bifid, and Quadroon. PMID- 1741375 TI - Solid-liquid phase boundaries of lens protein solutions. AB - We report measurement of the solid-liquid phase boundary, or liquidus line, for aqueous solutions of three pure calf gamma-crystallin proteins: gamma II, gamma IIIa, and gamma IIIb. We also studied the liquidus line for solutions of native gamma IV-crystallin calf lens protein, which consists of 85% gamma IVa/15% gamma IVb. In all four proteins the liquidus phase boundaries lie higher in temperature than the previously determined liquid-liquid coexistence curves. Thus, over the range of concentration and temperature for which liquid-liquid phase separation occurs, the coexistence of a protein crystal phase with a protein liquid solution phase is thermodynamically stable relative to the metastable separated liquid phases. The location of the liquidus lines clearly divides these four crystallin proteins into two groups: those in which liquidus lines flatten at temperatures greater than 70 degrees C: gamma IIIa and gamma IV, and those in which liquidus lines flatten at temperatures less than 50 degrees C: gamma II and gamma IIIb. We have analyzed the form of the liquidus lines by using specific choices for the structures of the Gibbs free energy in solution and solid phases. By applying the thermodynamic conditions for equilibrium between the two phases to the resulting chemical potentials, we can estimate the temperature-dependent free energy change upon binding of protein and water into the solid phase. PMID- 1741376 TI - Histones H2A/H2B inhibit the interaction of transcription factor IIIA with the Xenopus borealis somatic 5S RNA gene in a nucleosome. AB - A Xenopus borealis somatic 5S RNA gene was assembled with either the complete octamer of histones, (H2A/H2B/H3/H4)2, or the (H3/H4)2 tetramer of histones that comprises the central protein kernel of the nucleosome. Gel-mobility shifts, DNase I protection, and immunoblotting assays demonstrate that the class III transcription factor IIIA (TFIIIA) readily interacts with 5S DNA associated with the tetramer but that little or no binding is detected when 5S DNA is associated with the full octamer of histones. Thus, the presence of histones H2A and H2B in the 5S nucleosome significantly inhibits the interaction of TFIIIA with its cognate binding site within the 5S RNA gene. We propose that either the depletion of histones H2A and H2B from preexisting nucleosomes or the staged assembly of chromatin after replication in which a tetramer of histones H3/H4 associates with DNA before histones H2A/H2B will facilitate the binding of transcription factors to their cognate DNA sequences. PMID- 1741377 TI - Coexpression of mu and gamma 1 heavy chains can occur by a discontinuous transcription mechanism from the same unrearranged chromosome. AB - We previously documented that a single BCL1 leukemia cell can produce mu and gamma 1 immunoglobulin heavy chains with identical variable segments in an allelically excluded fashion without heavy chain constant region gene rearrangement. To understand the mechanism of dual mu/gamma 1 synthesis in BCL1 subclones, we have analyzed mature and pre-RNA at the nascent and steady-state levels. We find mu and gamma 1 sequences linked in pre-RNA. However, the primary mu and gamma 1 transcription units are about the same length (approximately 15 kilobases). Initiation of gamma 1 pre-RNA occurs upstream of C gamma 1 at sites identical to those seen in lipopolysaccharide/interleukin-4-induced normal B cells. We propose that dual mu/gamma 1 RNA synthesis occurs by a discontinuous transcription mechanism involving either trans-splicing or ligation of mu pre-RNA initiated 5' of the variable-diversity-joining region to gamma 1 pre-RNA initiated 5' of C gamma 1. PMID- 1741378 TI - Unconventional pharmacology of a neuronal nicotinic receptor mutated in the channel domain. AB - The putative channel-forming MII domains of the nicotinic, gamma-aminobutyric acid type A, and glycine receptors contain a highly conserved leucine residue. Mutation of this hydrophobic amino acid in the neuronal nicotinic receptor alpha 7 (Leu-247), reconstituted in Xenopus oocytes, modifies the ionic response to acetylcholine and alters desensitization. Furthermore, the Leu----Thr (L247T) mutant has two conducting states (46 pS and 80 pS), in contrast with the wild type (WT) receptor, which has only one (45 pS). We now show that this mutant possesses a rather paradoxical pharmacology: antagonists of the WT receptor such as dihydro-beta-erythroidin, hexamethonium, or (+)-tubocurarine elicit ionic currents when applied to the L247T alpha 7 mutant and these responses are blocked by alpha-bungarotoxin. Furthermore, prolonged application of acetylcholine causes desensitization in the WT but leads to a potentiation of the responses to acetylcholine or dihydro-beta-erythroidin in the mutant. These data are consistent with a scheme in which mutation of Leu-247 renders a desensitized state in the WT channel a conducting state. They also strengthen the proposal that, in the WT, some competitive antagonists may stabilize desensitized states. Finally, these observations may shed light on properties of other ion channels, in particular the glutamate receptors, which display multiple conductance levels associated with various pharmacological agents. PMID- 1741379 TI - Reconstitution of enzymatic activity from fragments of M1 RNA. AB - Certain fragments of M1 RNA, the catalytic subunit of RNase P from Escherichia coli, either have no enzymatic activity at all or have altered substrate specificity compared with that of the intact catalytic RNA. After simple mixing in vitro, many of these fragments of M1 RNA can reassociate with other fragments to form complexes that have enzymatic activity typical of wild-type M1 RNA. Furthermore, inactive M1 RNA molecules with internal deletions can be complemented in vitro by other inactive derivatives of M1 RNA that have nonoverlapping deletions. Thus, two inactive molecules of M1 RNA can interact to form an active RNA enzyme. Functional attributes can be assigned to various regions of M1 RNA when the reconstitution process is combined with assays for activity with different substrates. PMID- 1741380 TI - Fluorescence lifetime imaging of free and protein-bound NADH. AB - We introduce a methodology, fluorescence lifetime imaging (FLIM), in which the contrast depends on the fluorescence lifetime at each point in a two-dimensional image and not on the local concentration and/or intensity of the fluorophore. We used FLIM to create lifetime images of NADH when free in solution and when bound to malate dehydrogenase. This represents a challenging case for lifetime imaging because the NADH decay times are just 0.4 and 1.0 ns in the free and bound states, respectively. In the present apparatus, lifetime images are created from a series of phase-sensitive images obtained with a gain-modulated image intensifier and recorded with a charge-coupled device (CCD) camera. The intensifier gain is modulated at the light-modulation frequency or a harmonic thereof. A series of stationary phase-sensitive images each obtained with various phase shifts of the gain-modulation signal, is used to determine the phase angle or modulation of the emission at each pixel, which is in essence the lifetime image. We also describe am imaging procedure that allows specific decay times to be suppressed, allowing in this case suppression of the emission from either free or bound NADH. Since the fluorescence lifetimes of probes are known to be sensitive to numerous chemical and physical factors such as pH, oxygen, temperature, cations, polarity, and binding to macromolecules, this method allows imaging of the chemical or property of interest in macroscopic and microscopic samples. The concept of FLIM appears to have numerous potential applications in the biosciences. PMID- 1741381 TI - Protein affinity chromatography with purified yeast DNA polymerase alpha detects proteins that bind to DNA polymerase. AB - We have overexpressed the POL1 gene of the yeast Saccharomyces cerevisiae and purified the resulting DNA polymerase alpha polypeptide in an apparently intact form. We attached the purified DNA polymerase covalently to an agarose matrix and used this matrix to chromatograph extracts prepared from yeast cells. At least six proteins bound to the yeast DNA polymerase alpha matrix that did not bind to a control matrix. We speculate that these proteins might be DNA polymerase alpha accessory proteins. Consistent with this interpretation, one of the binding proteins, which we have named POB1 (polymerase one binding), is required for normal chromosome transmission. Mutations in this gene cause increased chromosome loss and an abnormal cell morphology, phenotypes that also occur in the presence of mutations in the yeast alpha or delta polymerase genes. These results suggest that the interactions detected by polymerase affinity chromatography are biologically relevant and may help to illuminate the architecture of the eukaryotic DNA replication machinery. PMID- 1741382 TI - Molecular characterization of two plant flavonol sulfotransferases. AB - cDNA clones coding for flavonol 3- and 4'-sulfotransferases (STs) were isolated by antibody screening of a cDNA expression library produced from poly(A)+ RNA extracted from terminal buds of Flaveria chloraefolia. Sequence analysis revealed full-length cDNA clones with open reading frames of 933 and 960 base pairs, which encode polypeptides containing 311 and 320 amino acids, respectively. This corresponds to a molecular mass of 36,442 Da for the 3-ST and 37,212 Da for the 4'-ST. Expression of these clones in Escherichia coli led to the synthesis of beta-galactosidase-ST fusion proteins having the same substrate and position specificities as those for the 3- and 4'-flavonol ST enzymes isolated from the plant. Comparison of the deduced amino acid sequence of the two clones revealed an overall identity of 69% in 311 amino acid residues. The two flavonol STs of F. chloraefolia also shared significant sequence similarities with steroid and aryl STs found in animal tissues and with the senescence marker protein 2 isolated from rat liver, suggesting an evolutionary link between plant and animal STs. PMID- 1741383 TI - Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter. AB - In the generation of the acutely transforming avian retrovirus E26, both myb and ets genes have been transduced, leading to the production of a Gag-Myb-Ets fusion protein. This co-occurrence of v-myb and v-ets oncogenes suggests that the two might have a functional relationship. To look for such a relationship, we tested the transcriptional activation activity of Myb alone or with coexpressed Ets-1 or Ets-2. Using the promoter of the v-Myb-inducible mim-1 gene as a target, we found that full-length c-Myb gene products were poor activators of transcription, while an oncogenic (truncated) form of this protein was a strong trans-activator. However, coexpression of Ets-2 with full-length or truncated forms of Myb greatly increased trans-activation. Coexpression of Ets-1, Fos, Jun, or Myc with Myb did not increase trans-activation of the mim-1 promoter. The ability of Myb and Ets-2 to transactivate was cooperative, since Ets-2 alone gave little or no activation. Bacterially synthesized Ets-2 protein was found to bind specifically to the mim-1 promoter, suggesting that it may be a target for both Myb and Ets proteins. Thus, Myb and Ets proteins can cooperate in transcriptional activation, and their co occurrence in the E26 virus may reflect a functional relationship between these two oncoproteins. Truncated forms of Myb may have a reduced need for cooperating factors such as Ets-2, and this might constitute an important mechanism associated with oncogenic activation. PMID- 1741384 TI - Two members of a conserved family of nuclear phosphoproteins are involved in pre mRNA splicing. AB - Monoclonal antibody 104 recognizes a subset of amphibian nuclear granules (B snurposomes) and active sites of RNA polymerase II transcription in vertebrates and invertebrates. Monoclonal antibody 104 reacts with a set of nuclear serine- and arginine-rich phosphoproteins (SR family) with strikingly conserved apparent molecular masses. The most abundant family members in human (SRp33) and Drosophila (SRp55) cell lines can replace one another as essential splicing factors in a human cell-free system. Each of these polypeptides can functionally replace human SF2, an essential splicing factor that also regulates 5' splice site selection of alternatively spliced pre-mRNAs in vitro. Drosophila SRp55 also functions as an alternative splicing factor in the human cell-free system. Analysis of cloned cDNAs shows that SRp55 and SF2 are highly related and reveals regions of similarity to genetically defined regulators of alternative splicing in Drosophila. These results suggest that the conserved SR family of phosphoproteins, which includes SRp55 and SF2, is involved in constitutive pre mRNA splicing and in the specificity of alternative splice site selection. PMID- 1741385 TI - Carcinogen-induced frameshift mutagenesis in repetitive sequences. AB - We have constructed plasmids pS3G-1 and pSG4 that contain single acetylaminofluorene adducts within contiguous runs of three (5'-CCCG1G2G3-3') and four (5'-CG1GGG4T-3') guanine residues, respectively. In Escherichia coli, the frequency of induced -1 frameshift mutations was strongly dependent on the position of modification: pS3G-G3 was approximately 100-fold and 10-fold more mutagenic than pS3G-G1 and pS3G-G2, respectively; pSG4-G4 was approximately 600 fold more mutagenic than pSG4-G1. Mutagenesis was SOS-dependent and was markedly reduced in bacteria that were proficient in nucleotide excision repair as compared to a repair-deficient uvrA6 mutant. DNA sequencing showed that -1 frameshift events in pS3G-1 consisted of either targeted mutations (greater than 90% of induced mutations) within the guanine sequence or semitargeted mutations (greater than 10%) in the 5' flanking repetitive cytosine sequence. Semitargeted events, which were observed when acetylaminofluorene modification was at G1 and G2, show that a lesion can reduce the fidelity of replication at positions 5' to its location on the template strand. No semitargeted frameshifts were observed in plasmid pSG4, which lacks a repetitive sequence 5' to the adduct. Our results are consistent with a model for frameshift mutagenesis in which the acetylaminofluorene adduct (i) allows accurate incorporation of cytosine opposite the bulky lesion during DNA synthesis and (ii) impedes elongation of primer/template termini formed opposite the adduct or 5' to the adduct on the template strand, providing increased opportunity for the formation of slipped frameshift intermediates. PMID- 1741386 TI - Resistance of primary isolates of human immunodeficiency virus type 1 to neutralization by soluble CD4 is not due to lower affinity with the viral envelope glycoprotein gp120. AB - Recombinant soluble CD4 (rsCD4) has potent antiviral activity against cell line adapted isolates of the human immunodeficiency virus type 1 (HIV-1) but low activity toward HIV-1 primary isolates from patients. A simple hypothesis proposed to explain this discrepancy, which questions the therapeutic utility of soluble CD4-based approaches, is that the major envelope glycoprotein, gp120, of patient virus has lower affinity for CD4 than does gp120 from laboratory viruses. To test this hypothesis, we have produced pairs of low- and high-passage HIV-1 isolates which, depending on culture passage history, display dramatically different sensitivities to neutralization by rsCD4. Here, we present evidence that the HIV-1 major envelope glycoprotein cDNAs cloned from one such isolate pair show only minor differences in their deduced gp120 primary structures, and these occur outside regions previously shown to be involved in CD4 interactions. In addition, recombinant gp120 from a low-passage rsCD4-resistant patient virus binds rsCD4 with high affinity, equal to that previously measured for recombinant gp120 from high-passage cell line-adapted virus isolates. These data indicate that differences in CD4-gp120 affinity do not account for rsCD4 resistance in HIV 1 recently isolated from patients. PMID- 1741387 TI - Telomeric arrays display high levels of heritable polymorphism among closely related plant varieties. AB - Tomato telomeres are composed of a terminal 7-base-pair tandem repeat and a closely liked 162-base-pair subtelomeric repeat (TGRI). Together, these repeats account for 2% of the total chromosomal DNA. Pulsed-field gel electrophoresis has been used to examine the long-range physical structure of these arrays in closely related varieties, and we report here that these arrays are undergoing heritable changes at a frequency as great as 2% per generation. Moreover, comparisons with other known hypervariable probes (e.g., human minisatellites and M13 sequences) revealed that telomeric sites are more variable than any other known region of the plant genome and can be used to distinguish closely related plant varieties (tomato and melon) that are otherwise very similar at the DNA level. The fact that the polymorphisms are inherited in a mendelian fashion suggests applications in genetic mapping of telomeres and identification of varieties. PMID- 1741388 TI - Over- and under-representation of short oligonucleotides in DNA sequences. AB - Strand-symmetric relative abundance functionals for di-, tri-, and tetranucleotides are introduced and applied to sequences encompassing a broad phylogenetic range to discern tendencies and anomalies in the occurrences of these short oligonucleotides within and between genomic sequences. For dinucleotides, TA is almost universally under-represented, with the exception of vertebrate mitochondrial genomes, and CG is strongly under-represented in vertebrates and in mitochondrial genomes. The traditional methylation/deamination/mutation hypothesis for the rarity of CG does not adequately account for the observed deficiencies in certain sequences, notably the mitochondrial genomes, yeast, and Neurospora crassa, which lack the standard CpG methylase. Homodinucleotides (AA.TT, CC.GG) and larger homooligonucleotides are over-represented in many organisms, perhaps due to polymerase slippage events. For trinucleotides, GCA.TGC tends to be under-represented in phage, human viral, and eukaryotic sequences, and CTA.TAG is strongly under-represented in many prokaryotic, eukaryotic, and viral sequences. The CCA.TGG triplet is ubiquitously over-represented in human viral and eukaryotic sequences. Among the tetranucleotides, several four-base-pair palindromes tend to be under-represented in phage sequences, probably as a means of restriction avoidance. The tetranucleotide CTAG is observed to be rare in virtually all bacterial genomes and some phage genomes. Explanations for these over- and under-representations in terms of DNA/RNA structures and regulatory mechanisms are considered. PMID- 1741389 TI - Murine fumarylacetoacetate hydrolase (Fah) gene is disrupted by a neonatally lethal albino deletion that defines the hepatocyte-specific developmental regulation 1 (hsdr-1) locus. AB - Homozygous deletion of the hepatocyte-specific developmental regulation 1 (hsdr 1) locus in mouse chromosome 7 results in perinatal death and a pleiotropic syndrome characterized by ultrastructural abnormalities of the liver and kidney, failure of induction of a number of specific transcription units in the liver and kidney during late gestation, and marked overexpression of an enzyme that defends against oxidative stress. Previously, the breakpoints of two albino (c) deletions (c14CoS and c1FAFyh) that genetically define hsdr-1 were localized, on a long range map, in the vicinity of the distal breakpoint of a viable albino deletion (c24R75M) that breaks proximally within the c locus. Here we report the use of a probe derived from a deletion breakpoint fusion fragment cloned from c24R75M/c24R75M DNA to clone a breakpoint fusion fragment caused by the c14CoS deletion. The proximal breakpoint of the c14CoS deletion was discovered to disrupt a gene (Fah) encoding fumarylacetoacetate hydrolase, the last enzyme in the tyrosine degradation pathway. All of the extant c deletions eliciting the hsdr-1 phenotype prevent expression of the Fah gene in the liver, and all but one disrupt the coding segment of the gene. Therefore, the Fah gene maps within or proximal to the hsdr-1 locus, as defined by deletion breakpoints, and disruption of this gene may be partially or completely responsible for the phenotypes associated with the hsdr-1 deletion syndrome. These mouse mutants may also provide models for the human genetic disorder hereditary tyrosinemia, which is associated with fumarylacetoacetate hydrolase deficiency and liver and kidney dysfunction. PMID- 1741390 TI - Role of gender, season, and familiarity in discrimination of conspecific song by zebra finches (Taeniopygia guttata). AB - Operant conditioning techniques were used to assess how gender and song familiarity affect song discrimination in adult zebra finches (Taeniopygia guttata). Twenty-five males and females, divided into five cohorts, were trained to discriminate between conspecific songs at different times of year. Males discriminating between their own and another song from their own aviary reached criterion in the fewest number of trials, followed by males discriminating between two songs from their own aviary, then by males discriminating between songs they had not heard before. Females discriminating between two songs from their own aviary required more trials than males to reach criterion, but, unlike in males, song familiarity did not have a significant effect on song discrimination by females. The number of trials required to reach criterion was greater in winter than in summer, suggesting a photoperiodic effect in what has been regarded as a nonphotoperiodic species. Gender, season, and familiarity appear to affect how zebra finches discriminate between conspecific songs. PMID- 1741391 TI - Hemispheric differences in avian song discrimination. AB - Auditory input to the right or left forebrain of adult male zebra finches (Taeniopygia guttata) was disrupted by lesioning the ipsilateral auditory relay nucleus of the thalamus. These birds were then presented with two kinds of auditory discriminations: (i) between their own song and the song of a cage mate; (ii) between two versions of an unfamiliar zebra finch song that differed only in the harmonic profile of one of the syllables. Right-side lesion birds did better than left-side lesion ones at discriminating between their own song and the song of a cage mate; left-side lesion birds did better on the harmonic profile task. We suggest that the two halves of the zebra finch brain process conspecific sounds differently, as seems to be the case for humans. PMID- 1741392 TI - Testosterone facilitates some conspecific song discriminations in castrated zebra finches (Taeniopygia guttata). AB - An experiment was designed to test for the influence of testosterone on song discriminations. We found that testosterone did have an effect, which interacted with practice and the nature of the stimuli. Fourteen adult castrated zebra finches (Taeniopygia guttata) were grouped into seven pairs. In each pair, one bird was implanted with a testosterone-filled silastic tube and the other was implanted with an empty silastic tube. They were then trained on a go/no-go operant task to discriminate between bird songs in six consecutive experiments. The songs to be discriminated were as follows: experiment 1, two canary song segments; experiment 2, the bird's own song and that of the other member of the pair; experiment 3, the same two songs as in experiment 2 but with reversed stimulus-response contingencies; experiment 4, two other zebra finch songs; experiment 5, another two zebra finch songs; and experiment 6, another two canary song segments. There were no reliable learning differences between birds treated with testosterone or with an empty silastic in experiments 1 and 3-6. However, in experiment 2, testosterone-treated birds mastered the discrimination between their own song and the song of the other member of the pair in fewer trials than birds treated with empty silastics. We suggest that a song's ability to control the behavior of male zebra finches is influenced by the nature of the song, prior experience with the training paradigm, and hormone levels. PMID- 1741393 TI - Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants. AB - Vulnerability of specific brain regions and neuronal populations is a characteristic feature of Alzheimer disease and Down syndrome. Cholinergic neurons of the basal forebrain degenerate in both disorders. The basis for neuronal degeneration is unknown. Mouse trisomy 16 (Ts 16) is an animal model of Down syndrome. We sought an experimental system in which the survival and development of Ts 16 basal forebrain cholinergic neurons could be examined beyond the fetal period. As Ts 16 mice do not survive birth, we transplanted fetal Ts 16 and control basal forebrain into the hippocampus of young adult mice. Transplanted neurons survived and grew neurites in all grafts. Over time, we observed selective atrophy of cholinergic neurons in Ts 16 grafts. Denervation of the hippocampus produced a significant increase in the size of Ts 16 cholinergic neurons. This suggests that hippocampal-derived neurotrophic factors acted to prevent degeneration. beta/A4-amyloid-containing plaques were not seen. Ts 16 provides a model of spontaneous, genetically determined neurodegeneration that may be used to understand better the molecular pathogenesis of neuronal dysfunction in Alzheimer disease and Down syndrome. PMID- 1741394 TI - Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. AB - Combinatorial labeling of probes (i.e., with two or more different reporters) increases the number of target sequences that can be detected simultaneously by fluorescence in situ hybridization. We have used an epifluorescence microscope equipped with a digital imaging camera and computer software for pseudocoloring and merging images to distinguish up to seven different probes using only three fluorochromes. Chromosome-specific centromere repeat clones and chromosome specific "composite" probe sets were generated by PCR in which different mixtures of modified nucleotides, including fluorescein-conjugated dUTP, were incorporated. Cosmid clones were labeled similarly by nick-translation. The technique has been used to delineate the centromeres of seven different human chromosomes, on both 4',6-diamidino-2-phenylindole-stained metaphase spreads and interphase nuclei, to map six cosmid clones in a single hybridization experiment and to detect chromosome translocations by chromosome painting. Multiparameter hybridization analysis should facilitate molecular cytogenetics, probe-based pathogen diagnosis, and gene mapping studies. PMID- 1741395 TI - Early molecular events in the induction phase of contact sensitivity. AB - To assess changes in epidermis-derived cytokine mRNA levels early in the afferent phase of allergic contact sensitivity, total epidermal mRNA was analyzed at various times after painting skin with haptens. We used a sensitive reverse transcriptase-polymerase chain reaction technique to quantitatively compare the regulation patterns of the following mRNAs: class II major histocompatibility complex I-A alpha, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1 alpha, IL-1 beta, interferon (IFN) gamma, granulocyte/macrophage colony stimulating factor, IFN-induced protein 10, and macrophage inflammatory protein 2. Enhanced Langerhans cell-derived IL-1 beta mRNA signals were detected as early as 15 min after skin painting with allergens. TNF-alpha, IFN-gamma, and granulocyte/macrophage colony-stimulating factor mRNAs were found to be upregulated after application of allergens, irritant, and tolerogens, but class II major histocompatibility complex I-A alpha, IL-1 alpha, IL-1 beta, IFN-induced protein 10, and macrophage inflammatory protein 2 mRNAs were upregulated only after allergen painting. Depletion of specific cell populations demonstrated that Langerhans cells were the primary source of the IL-1 beta and class II major histocompatibility complex I-A alpha mRNAs, keratinocytes were the primary source of TNF-alpha, IL-1 alpha, IFN-induced protein 10, and macrophage inflammatory protein 2, and infiltrating T lymphocytes were the source of IFN-gamma. Relevance of the molecular findings was demonstrated by the identification of biologically active IL-1 alpha and immunoreactive TNF-alpha in culture supernatants. These studies demonstrate that Langerhans cell-derived and certain keratinocyte-derived cytokine mRNAs are selectively upregulated by allergens in the very early afferent phase of contact sensitivity. PMID- 1741396 TI - The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs. AB - Cleavage stimulation factor is one of the multiple factors required for 3'-end cleavage of mammalian pre-mRNAs. We have shown previously that this factor is composed of three subunits with estimated molecular masses of 77, 64, and 50 kDa and that the 64-kDa subunit can be UV-crosslinked to RNA in a polyadenylylation signal (AAUAAA)-dependent manner. We have now isolated cDNAs encoding the 64-kDa subunit of human cleavage stimulation factor. The 64-kDa subunit contains a ribonucleoprotein-type RNA binding domain in the N-terminal region and a repeat structure in the C-terminal region in which a pentapeptide sequence (consensus MEARA/G) is repeated 12 times and the formation of a long alpha-helix stabilized by salt bridges is predicted. An approximately 270-amino acid segment surrounding this repeat structure is highly enriched in proline and glycine residues (approximately 20% for each). When cloned 64-kDa subunit was expressed in Escherichia coli, an N-terminal fragment containing the RNA binding domain bound to RNAs in a polyadenylylation-signal-independent manner, suggesting that the RNA binding domain is directly involved in the binding of the 64-kDa subunit to pre mRNAs. PMID- 1741397 TI - Ontogeny of a biological clock in Drosophila melanogaster. AB - Drosophila melanogaster born and reared in constant darkness exhibit circadian locomotor activity rhythms as adults. However, the rhythms of the individual flies composing these populations are not synchronized with one another. This lack of synchrony is evident in populations of flies commencing development at the same time, indicating that a biological clock controlling circadian rhythmicity in Drosophila begins to function without a requirement for light and without a developmentally imparted phase. It is possible to synchronize the phases of rhythms produced by dark-reared flies with light treatments ending as early as the developmental transition from embryo to first-instar larva: Light treatments occurring at developmental times preceding hatching of the first instar larva fail to synchronize adult locomotor activity rhythms, while treatments ending at completion of larval hatching entrain these rhythms. The synchronized rhythmic behavior of adult flies receiving such light treatments suggests that a clock controlling circadian rhythms may function continuously from the time of larval hatching to adulthood. PMID- 1741398 TI - Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells. AB - A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2 positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction. PMID- 1741399 TI - Termination efficiency at rho-dependent terminators depends on kinetic coupling between RNA polymerase and rho. AB - Rho-dependent terminators constitute one of two major classes of terminators in Escherichia coli. Termination at these sites requires the concerted action of RNA polymerase and rho protein. We present evidence that the efficiency of termination at these sites is governed by kinetic coupling of the rate of transcription of RNA polymerase and the rate of action of rho protein. Termination experiments in vitro indicate that termination efficiency at a rho dependent terminator is an inverse function of the rate of elongation of RNA polymerase, and each of the mutant phenotypes can be accounted for by the altered rate of elongation of the mutant RNA polymerase. Experiments in vivo show that fast-moving mutant RNA polymerases are termination deficient, while slow-moving mutant RNA polymerases are termination proficient and can suppress the termination deficiency of a slow-acting mutant rho protein. Because of the close coupling of rho action with RNA polymerase, small changes in the elongation rate of RNA polymerase can have very large effects on termination efficiency, providing the cell with a powerful way to modulate termination at rho-dependent terminators. PMID- 1741400 TI - Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. AB - A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans. PMID- 1741401 TI - Polymorphism in a second ABC transporter gene located within the class II region of the human major histocompatibility complex. AB - Recent studies have identified genes within the major histocompatibility complex (MHC) that may play a role in presentation of antigenic peptides to T cells. We have previously described RING4, a gene within the human MHC class II region that has sequence homology with members of the ABC ("ATP-binding cassette") transporter superfamily. We now report the nucleotide sequence of RING11, a second ABC transporter gene located approximately 7 kilobases telomeric to RING4, RING11 is gamma-interferon inducible, a property shared with other genes involved in antigen presentation. Comparison between the amino acid sequences of RING11 and RING4 reveals strong homology. We propose that they form a heterodimer that transports peptides from the cytoplasm into the endoplasmic reticulum. We have identified two RING11 alleles, which differ in the length of their derived protein sequence by 17 amino acids. The more common of these alleles is present in a Caucasoid population at a frequency of 79%. PMID- 1741402 TI - A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. AB - Using a DNA probe from the DNA-binding portion of the NF-IL6 gene and an antibody against the DNA-binding domain of NF-IL6, we isolated a gene homologous to NF-IL6 in the DNA-binding and leucine zipper domains. This intronless gene, termed NF IL6 beta encodes a 269-amino acid protein with a potential leucine zipper structure, and the gene product can bind to the CCAAT homology as well as the viral enhancer core sequence, as in the cases of NF-IL6 and C/EBP. This gene is expressed at an undetectable or a minor level in normal tissues but is induced by lipopolysaccharide or inflammatory cytokines, as in the case of NF-IL6. NF-IL6 beta easily forms a heterodimer with NF-IL6 in vitro and the heterodimeric complex binds to the same DNA sequence as the respective homodimers. When examined by transient luciferase assays, NF-IL6 beta is consistently a stronger transactivator than NF-IL6. Furthermore, NF-IL6 beta shows a synergistic transcriptional effect with NF-IL6. These data suggest that NF-IL6 beta is an important transcriptional activator in addition to NF-IL6 in regulation of the genes involved in the immune and inflammatory responses. PMID- 1741403 TI - Suppression of deregulated c-MYC expression in human colon carcinoma cells by chromosome 5 transfer. AB - Two-thirds of sporadic colon carcinomas express elevated levels of the c-MYC protooncogene. In addition, most colon carcinoma cell lines show constitutive elevated expression (10- to 40-fold over normal) of MYC RNA and protein that is not modulated in response to a mitogenic stimulus. Indirect immunofluorescence has been used to detect c-MYC protein in such cell lines, in hybrid cells resulting from fusions of such lines with cells that regulate MYC normally, and in carcinoma cells to which a normal copy of chromosome 5 has been transferred by microcell fusion. The deregulated expression of c-MYC is suppressed by fusion with a cell that regulates MYC normally. In addition, transfer of chromosome 5 by microcell fusion results in suppression of deregulated expression. Suppressed cells are no longer tumorigenic in nude mice. Loss of the transferred chromosome results in reexpression of the tumorigenic phenotype and in constitutive elevated expression of MYC. These data indicate that function of a tumor-suppressor gene on chromosome 5 is necessary for the regulated expression of MYC in at least some colon cells. Loss of this suppressor results in deregulated MYC expression and is a necessary, but most likely not sufficient, event for the expression of the tumorigenic phenotype in a subset of colon carcinomas. PMID- 1741404 TI - Internal-image anti-idiotype HIV-1gp120 antibody in human immunodeficiency virus 1 (HIV-1)-seropositive individuals with thrombocytopenia. AB - Anti-CD4 antibody was found in 30% of human immunodeficiency virus (HIV-1) seropositive thrombocytopenic patients compared with 5% of nonthrombocytopenic seropositive patients (chi 2 = 21.7, P less than 0.001) and was shown by the following observations to contain internal-image anti-idiotype antibody (Ab2) directed against the antibody (Ab1) to gp120, the HIV-1 envelope glycoprotein that binds to CD4: (i) affinity-purified anti-CD4 (Ab2) bound to affinity purified anti-HIV-1gp120 (Ab1) on solid-phase radioimmunoassay, and binding could be blocked by recombinant CD4 (rCD4) as well as recombinant gp120 (rgp120); (ii) F(ab')2 fragments of Ab1 inhibited the binding of Ab2 to rCD4; (iii) Ab2 inhibited the binding of Ab1 to HIV-1 beads; (iv) Ab2 inhibited the binding of Ab1 to gp120 on immunoblot; (v) Ab2 bound to the CD4 receptor on a CD4-bearing T cell line, H9; (vi) Ab3 (anti-rgp120) could be produced in vivo by immunizing mice with Ab2, and binding of Ab3 to rgp120 could be blocked with rCD4; and (vii) three different Ab2 preparations bound to two different homologous Ab1 preparations. Ab1 or Ab2 alone did not bind to platelets, whereas the idiotype anti-idiotype complex did bind to platelets in a concentration-dependent manner. Binding of the internal-image complex was 10-fold greater than that of a non internal-image Ab1-Ab2 complex composed of anti-HIV-1gp120 and anti-anti-HIV 1gp120. Thus, patients with HIV-1 thrombocytopenia contain internal-image idiotype-anti-idiotype complexes that could be affecting CD4 cell number or function, inhibiting HIV-1 binding to CD4 cells or contributing to HIV-1 thrombocytopenia. PMID- 1741405 TI - Phenotypic plasticity in adult sympathetic neurons: changes in neuropeptide expression in organ culture. AB - Vasoactive intestinal peptide (VIP)-like immunoreactivity is present at low levels in the superior cervical ganglion of the adult rat, where immunostained neural processes, but only an occasional immunostained cell body, are found. However, when ganglia are maintained for 24 or 48 hr in organ culture, their content of VIP-like immunoreactivity increases 6- or 31-fold, respectively. When examined at 24 hr, the increase in VIP-like immunoreactivity is totally blocked by an inhibitor of RNA or protein synthesis. Many neuronal cell bodies and processes with immunoreactivity for VIP and the related peptide histidine isoleucine amide (PHI) are seen in cultured ganglia. In addition, VIP/PHI mRNA is abundant in cultured ganglia but only barely detectable in ganglia prior to culture. Under the same culture conditions, neuropeptide Y-like immunoreactivity increases to a small extent, and tyrosine hydroxylase activity and total ganglion protein remain unchanged. These results support the idea that adult sympathetic neurons exhibit plasticity in neuropeptide expression and that this plasticity, in the case of VIP, depends on changes in gene expression. PMID- 1741406 TI - A human Id-like helix-loop-helix protein expressed during early development. AB - The interaction of helix-loop-helix (HLH) proteins is known to regulate the differentiation of several different tissues, including mammalian muscle and the insect peripheral nervous system. In myoblasts, the products of myogenic HLH genes such as MyoD and ubiquitous HLH proteins such as E12 are present at constant levels throughout development. An E12 monomer and a MyoD monomer form a DNA binding heterodimer that activates muscle-specific genes. These two proteins are unable to dimerize in proliferating myoblasts because a negative regulator HLH protein, Id, is present. We now report the sequence and structure of a human HLH gene related to Id, which has been designated Id-2. Two prominent Id-2 RNA molecules of 2.5 and 1.3 kilobases were found in a number of different human normal and neoplastic tissues. We believe the larger RNA is a precursor of the 1.3-kilobase mRNA that encodes an Id-2 protein of 134 amino acids. The HLH region of the Id-2 protein is 90% homologous to that of myogenic Id, but the homology is much less extensive outside the HLH region. The Id-2 gene is highly expressed during early fetal development in several tissues, including those of the central nervous system, but is not expressed in the corresponding mature tissues. Id-2 expression is modulated in association with retinoic acid-induced ganglionic differentiation of the neuroblastoma cell line SMS-KCNR. These findings suggest that Id-2 is an inhibitor of tissue-specific gene expression, although its distinctive pattern of expression during development suggests a role different from that of Id. PMID- 1741407 TI - Seasonal changes in the function of the hypothalamic-pituitary-testicular axis in the Syrian hamster. PMID- 1741408 TI - Endothelin 1: mitogenic activity on pulmonary artery smooth muscle cells and release from hypoxic endothelial cells. AB - Endothelin, a recently described vasoconstrictor, has been shown to be a mitogen for vascular smooth muscle cells from systemic arteries and might play a role in pulmonary vascular remodeling produced by chronic exposure to hypoxia. We examined the effects of endothelin on proliferation of pulmonary artery smooth muscle cells and the effects of hypoxia and normoxia on the synthesis and secretion of endothelin by endothelial cells. Our results indicate that endothelin significantly increased the incorporation of [3H]thymidine by porcine pulmonary artery smooth muscle cells (122 +/- 4% to 168 +/- 13% of controls, with concentrations of endothelin from 1 to 1000 ng/ml). When tested on bovine pulmonary artery smooth muscle cells, endothelin increased [3H]thymidine incorporation over controls by approximately 140%; cell counts were increased by 107 +/- 4% and 122 +/- 7% at doses of 100 ng/ml and 1000 ng/ml, respectively. The secretion of endothelin by porcine endothelial cells was not affected by hypoxia (3520 +/- 138 pg/ml/10(6) cells in hypoxia vs 3770 +/- 326 pg/ml/10(6) cells in normoxia). Transforming growth factor-beta 1 stimulated the release by normoxic, and to a lesser degree by hypoxic, porcine endothelial cells of endothelin (4716 +/- 43 pg/ml/10(6) cells vs 4074 +/- 106 pg/ml/10(6) cells). Taken together, our results indicate that endothelin is weakly mitogenic for pulmonary artery smooth muscle cells, but may not significantly contribute to the remodeling seen in hypoxic pulmonary hypertension. PMID- 1741409 TI - A chemical method for intracellular loading of the calcium indicator aequorin in mammalian skeletal muscle. AB - The bioluminescent calcium indicator aequorin was loaded into bundles of skeletal muscle fibers from the rat extensor digitorum longus by macroinjection, a technique previously applied only to cardiac muscle. After loading, the amplitude and time course of the twitch returned to control values, indicating lack of damage to the fibers. Individual light signals (i.e., calcium transients) were recorded during each twitch or tetanus without the need for signal averaging. The calcium transients obtained were qualitatively and quantitatively similar to those reported previously with microinjection of aequorin. Our data suggest that macroinjection may be the method of choice for loading aequorin into mammalian skeletal muscle. PMID- 1741410 TI - Human retinal vascular cells differ from umbilical cells in synthetic functions and their response to glucose. AB - Cell culture systems have commonly been used to study mechanisms implicated in the pathogenesis of diabetic retinopathy, but the great majority of cell preparations used have been either of nonhuman retinal origin or nonretinal human origin. Because of questions of species and organ specificity in the function of cells of vascular origin, in this study, cultured microvascular endothelial cells (HREC), pericytes (HRPC), and pigment epithelial cells from the postmortem human retina, and endothelial cells from human umbilical vein (HUVEC) were evaluated with respect to cell proliferation, and secretory products potentially important in diabetic retinopathy, i.e., prostaglandins (PG) and plasminogen activators (PA), normalized to DNA content/well, under both basal (5 mM) and high (25 mM) glucose conditions. Glucose (25 mM) reduced DNA content similarly in both types of endothelial cells, had a lesser effect on HRPC, and did not significantly alter the proliferation of pigment epithelial cells. Basal secretion of PGI2 (measured as 6-keto-PGF1 alpha) was in the order HRPC much greater than HREC greater than HUVEC, whereas PGE2 secretion was in the order HREC much greater than HRPC greater than HUVEC. Glucose (25 mM) stimulated PGI2 secretion by HRPC, but not by either type of endothelial cell, and enhanced PGE2 secretion by HREC, but not by HUVEC or HRPC. Release of plasminogen activator activity differed between HUVEC and HREC under basal conditions and addition of 25 mM glucose stimulated release only from HREC. Glucose (25 mM) stimulated PA secretion by HREC, but not by HUVEC. These findings provide evidence that human retinal pericytes are an important source of prostacyclin, and that there are differences between HREC and HUVEC with respect to secretory functions and their modulation by glucose, indicating regional specificity of these functions. Extrapolation to human retinal vascular cells from experiments using cells from heterologous vascular beds to draw inferences about the pathophysiology of diabetic retinopathy are not valid for these cellular functions. PMID- 1741411 TI - Developmental delay of lingual lipase expression after guanethidine-induced sympathectomy. AB - Rat lingual lipase increases during postnatal development. To evaluate the role of the sympathetic nervous system in the control of lingual lipase during development, suckling rats were chemically sympathectomized by chronic treatment with guanethidine. This treatment was found to be effective in suppressing the developmental increase of lingual lipase. The effect was age dependent and also related to the dose of guanethidine given (i.e., the higher the dose, the more effective the suppression is, up to 40 micrograms/g body wt). The effect of guanethidine on lingual lipase suppression was not a result of induced stress, since simultaneous treatment with RU-38486, a known glucocorticoid receptor antagonist, did not prevent the decrease in lingual lipase activity. Ephedrine, a known sympathomimetic agent, restored the lingual lipase to a near normal level in guanethidine-treated animals, confirming that guanethidine acts through the sympathetic nerves. Furthermore, histochemical studies showed that guanethidine treatment resulted in the reduction or elimination of catecholaminergic fibers in the von Ebner's glands. The effect of guanethidine was found to be transient, in that the lingual lipase activity showed complete recovery upon withdrawal of the treatment for 1 week. Together, the results indicated that sympathetic nerves have an important regulatory role in lingual lipase in rat pups during development. PMID- 1741412 TI - A simple, single, trial-learning paradigm for conditioned increase in natural killer cell activity. AB - A change in natural killer (NK) cell activity can be conditioned with one trial learning when conditioned stimulus (CS) precedes the unconditioned stimulus (US). To avoid the problems associated with two reexposures in our earlier studies, we have developed a reliable and simple conditioning protocol utilizing the one trial learning and one reexposure to the odor CS. The conditioned change in NK cell activity was significantly different (P less than 0.05) from the control groups of mice. The paradigm is short and simple in that the conditioned change could be demonstrated within 3 days. We have also compared the effects of temporal association of CS and US on conditioned increase in NK cell activity. Forward conditioning (CS preceded the US) demonstrated a conditioned change, but the backward conditioning protocol did not. The paradigm provides a reliable approach to the study of mechanisms of the phenomenon of odor-NK conditioning. PMID- 1741413 TI - Inhibition of cell metabolism by a smokeless tobacco extract: tissue and species specificity. AB - Smokeless tobacco contains a nonnicotine inhibitor of posttranslational modification of collagen (hydroxylation of [3H]proline) by cultured chick embryo tibias and osteoblasts. This study was undertaken to determine whether a methanol extract of smokeless tobacco (STE) containing the inhibitor has similar effects on collagen-producing cells and tissues other than bone. Its effects on DNA synthesis and cell proliferation (incorporation of [3H]thymidine) were also determined. Frontal bone, aorta, and cartilage were incubated for 2 days in medium containing STE. Glycolysis (lactate production) was stimulated by 80% in cartilage, but was not affected in the other tissues; medium alkaline phosphatase activity was unaffected. In frontal bone and cartilage, [3H] hydroxyproline content was decreased 88% and 57%, respectively, and [3H]proline content was decreased 68% and 37%, respectively; neither was affected in the aorta. Confluent cultures of collagen-producing mouse fibroblasts or primary osteoblasts obtained from chick embryo calvarias were incubated for 2 days in medium containing increasing concentrations of STE. Glycolysis and DNA synthesis were not affected. Cell proliferation was unaffected in fibroblasts, but was inhibited (34%) at the highest STE concentration in osteoblasts. AIPase activity was not detectable in fibroblast medium, but was decreased up to 72% in osteoblast medium. Inhibition of collagen synthesis by STE was concentration related in both cell types. At the highest concentration, [3H] hydroxyproline and [3H]proline contents in the cell layers were decreased to the following respective values: fibroblasts 56% and 45% and osteoblasts 50% and 29%, respectively. When incubation with STE was discontinued for 1 day, recovery did not occur. These findings suggest that inhibition of collagen synthesis by STE is not specific for bone, that collagen producing cells are directly affected, and that recovery is not immediate. This inhibitor could contribute to the periodontal disease often seen in users of smokeless tobacco. Its identification and removal would produce a safer product. PMID- 1741414 TI - Serum zinc in aging germ-free and conventional rats. AB - Zinc nutritional status appears to decline with age in humans and rodents. Since germ-free rats outlive their conventional counterparts in better health, serum Zn levels were determined in male germ-free and conventional Lobund Wistar rats in samples originating from the Lobund Aging Study. Starting at 5 months of age, germ-free rats showed significantly higher serum Zn levels than did their conventional counterparts. In conventional rats sacrificed up to 30 months of age in apparently good health, serum Zn levels showed no effect of age, while a slight but significant increase with age was observed in the germ-free rats. In healthy germ-free adults (6-24 months of age), serum Zn concentrations were approximately 25% higher than those in comparable conventional animals. In conventional rats 18-30 months of age (average, 24.5 months), sacrificed because of an obvious moribund condition, serum Zn levels were significantly lower than those in rats of the same age range (average, 24.9 months) that were obviously healthy. Results suggest that the often observed higher absorptive capacity of the germ-free gut might have contributed to higher serum Zn levels, and that a decline in serum Zn concentration with age may be a consequence, rather than a causative factor, of declining health. PMID- 1741415 TI - Octopamine and phenylethylamine inhibit prolactin secretion both in vivo and in vitro. AB - Trace amines are a group of biogenic amines that are present in neural tissue in concentrations ranging from 0.1 to 100 ng/g. In the present work, we examined the action of two trace amines, octopamine and phenylethylamine, which are found in the hypothalamus, on pituitary hormone secretion in different experimental situations in vivo and in dispersed anterior pituitary cells. Both octopamine and phenylethylamine decreased high prolactin levels due to swimming or immobilization stress without affecting other adenohypophysial hormones. With regard to the hypoprolactinemic potencies in the immobilization stress model, it was observed that p-tyramine, another trace amine, was as potent as octopamine. Phenylethylamine was the least effective. To evaluate the site of action of the effect described, the three trace amines were tested in dispersed anterior pituitary cell cultures in vitro. Tyramine and octopamine reduced prolactin secretion in a concentration-dependent manner, at concentrations of 10(-8) to 10( 5) M, whereas the hypoprolactinemic effect observed for phenylethylamine was very weak. In pharmacologic experiments, neither octopamine nor phenylethylamine reduced prolactin release when dopaminergic receptors were blocked. This could mean that their hypoprolactinemic action was mediated through the release of dopamine, or it could be a direct action at a dopaminergic receptor. This is the first description of a specific endocrine action both in vivo and in vitro for octopamine and phenylethylamine. Further studies are needed to ascertain the physiologic or pathologic implication of these findings. PMID- 1741416 TI - Selective regulation of eosinophil degranulation by interleukin 1 beta. AB - Recent evidence confirms that cytokines such as IL-1, IL-4, IL-5, and GM-CSF may enhance or inhibit eosinophil function. Functions that are susceptible to modulation include eosinophil-mediated antibody-dependent damage of helminthic parasites, oxidative metabolism and degranulation. We have employed IgG and IgE coated Sepharose beads to investigate selective modulation of IgG and IgE mediated enzyme release by IL-1 beta. Both IgG and IgE-coated beads induced release of granular enzymes beta-glucuronidase and arylsulfatase. Enzyme release from IgG-stimulated eosinophils was inhibited by preincubation with IL-1 beta (100 pg/ml, P less than or equal to 0.05). In contrast, enzyme release by IgE stimulated eosinophils was enhanced by IL-1 beta (100 pg/ml, P less than or equal to 0.05). These studies support the hypothesis that IL-1 beta has specific selective actions on eosinophil function. Furthermore, these actions on particle stimulated enzyme release suggest that IgG and IgE mediated processes in eosinophils are differentially regulated. PMID- 1741417 TI - Ultraviolet radiation in the treatment of skin disease. PMID- 1741418 TI - Dosimetric evaluation of a two-dimensional, arc electron, pencil-beam algorithm in water and PMMA. AB - The accuracy of dose calculations from a pencil-beam algorithm developed specifically for arc electron beam therapy was evaluated at 10 and 15 MeV. Mid arc depth-doses were measured for 0 degrees and 90 degrees arcs using 12 and 15 cm radius cylindrical water phantoms. Calculated depth-doses for the 90 degrees arced beams in the build-up region were as much as 3% less than measured values; the maximum dose was similar in magnitude but at a greater depth; and the therapeutic depth, R80, was 2-4 mm deeper. Calculated values of output (dose per monitor unit) at the depth of the maximum calculated dose were compared with measured values; for arcs ranging from 0-90 degrees, 12 and 15 cm radius water phantoms, and collimator widths of 4, 5 and 6 cm, results showed differences as great as 7%. Isodose countours for a 90 degrees arc were also measured in a 15 cm radius PMMA phantom. At the depth of maximum dose the algorithm predicted doses in the penumbral regions, both with and without collimation, which agreed within a few per cent of measured values. The largest discrepancies were 5%, which occurred in the penumbral portion of the depth-dose fall-off region. Differences between measurement and calculation are not believed to be clinically significant and are believed to be primarily due to the fact that the algorithm models neither large-angle scattering nor the effects of range straggling on the pencil beam dose distribution. PMID- 1741419 TI - Field matching of electron beams using plastic wedge penumbra generators. AB - We describe the use of polystyrene wedges to match adjacent electron beams with improved dose uniformity. These wedges were designed to increase the penumbra width at the field junction from about 1.5 to about 3.5 cm, to achieve dose uniformity. Measurements using thermoluminescent dosimeters (TLD) and therapy localization film showed that the use of polystyrene wedges (penumbra generators) produced only a small increase (less than 3%) in the surface dose and a small increase (less than 1%) in the x-ray contamination. Without wedges at the field junction, lateral mismatching of beam edges by 2 or 3 mm may introduce high dose variations (120% or more or 50% or less). Similar 2-3 mm set-up errors did not cause more than +/- 5% dose variations when plastic wedges were used to match the fields. These wedges are particularly useful when matching fields of different beam energies or matching fields on curved surfaces, such as the chest wall. PMID- 1741420 TI - Transport calculations of depth-dose distributions for gadolinium neutron capture therapy. AB - Depth-dose distributions were calculated for thermal and epithermal neutron fluence and capture gamma ray dose rates using a two-dimensional neutron-coupled gamma-ray transport code (DOT 3.5) for gadolinium neutron capture therapy. The results show that (i) a capture gamma-ray dose rate of 10 Gy h-1 was obtained with a thermal neutron fluence rate of 1.5 x 10(9) cm-2 s-1 in a simulated tumour containing 5000 PPM gadolinium placed near the surface of a water phantom, (ii) deep-seated tumours may be treated with epithermal neutrons, and (iii) gadolinium neutron capture therapy appears to achieve comparable dose distributions to those of boron neutron capture therapy. PMID- 1741421 TI - Dose distributions of x-ray fields as shaped with multileaf collimators. AB - Multileaf collimators (MLC) with various blade widths were simulated using standard cerrobend blocks, and three-dimensional dose computations were carried out to study the resultant radiation field edges. Film measurements made with 6 and 18 MV x-ray beams were compared with calculations that employed a three dimensional Fourier convolution. A spatial accuracy of better than 3 mm was found in the 50% isodose line of the penumbral region with a calculation voxel size of 5 mm x 5 mm x 5 mm. The computer simulation was used to study the deviation of the calculated 50% isodose line from the desired geometric field edge using various MLC blade positions. The study suggests that multileaf collimation to the outside of the desired field edge will lead to overdose outside the field, whereas multileaf collimation to the inside of the desired field edge will lead to underdose inside the field. When the direction of travel of the leaves with respect to the field edge is near 45 degrees, the 50% isodose of a multileaf collimated beam will fall close to the desired edge with no underdose when the leaf corners are allowed to insert into the desired field edge by 1.2 mm for 6 MV x-rays and 1.4 mm for 18 MV x-rays using a 1 cm wide leaf. These blade offsets account for the scattering of photons and electrons in the medium within the penumbral region. PMID- 1741422 TI - Dielectric properties of the system bovine albumin: urea: betaine in aqueous solution. AB - Urea (about 5 mol l-1) causes an approximately five-fold increase of the dielectric increment of bovine serum albumin at 20 degrees C. The increase is reversed by betaine (about 2.5 mol l-1), or prevented if urea and betaine are added together. This result can be seen as an electric counterpart to the protective role of osmolytes which are secreted by cells and tissues subjected to various types of internal or environmental stress. PMID- 1741423 TI - A quick accurate method for measuring the microwave dielectric properties of small tissue samples. AB - A resonant cavity perturbation technique has been developed which provides a quick, simple and accurate method of measuring the microwave dielectric properties of small, easily prepared samples of tissues, tissue-simulating materials and biological fluids. The method gives dielectric properties averaged over the sample volume. The measurement accuracy with the apparatus used is +/- 2.2% for relative permittivity and +/- 3.5% for the loss factor for most tissue and biological material samples. With appropriate basic microwave equipment the method can be applied over the 1.5-6 GHz range of frequencies of interest for active and radiometric tissue microwave imaging. PMID- 1741424 TI - Dielectric properties of female human breast tissue measured in vitro at 3.2 GHz. AB - Complex permittivities of in vitro diseased and undiseased human female breast tissues have been measured at 3.2 GHz using a resonant cavity technique. Ranges of dielectric properties and water contents of these tissues are presented. Experimental data are compared with models predicted from mixture equations. Measured permittivity data lie within limits set by two-phase mixture theory, but some conductivity data are in excess of those expected for a mixture of saline and protein. At any particular microwave frequency in all tissue of a given type, the relationship between permittivity and conductivity may be parametrized using the Debye relaxation equations. For each breast tissue type a characteristic relaxation frequency was calculated and found to be lower than that of physiological saline at the same temperature. It is concluded that the dielectric relaxation of tissue water is not the only dispersive process occurring at this frequency: dielectric relaxation of bound water and the tail end of a beta dispersion may also contribute to the dielectric properties. The similarity of the dielectric properties of benign and malignant breast tumours measured in this work suggest that in vivo dielectric imaging methods will not be capable of distinguishing them. PMID- 1741425 TI - Measurement of the thermal diffusivity of human epidermis by studying thermal wave propagation. AB - The thermal diffusivity of dry human epidermis was determined in vitro by studying thermal wave propagation in thin epidermal layers at frequencies between 10 and 200 Hz. Transmission measurements were performed on samples applied to a plane copper support at the underside of which thermal waves were generated by means of a square voltage controlled power transistor. Additionally, measurements were performed on epidermal layers with metal and air backing, in which thermal waves were generated by the absorption of intensity modulated light in a thin, superficially applied graphite layer (short and open circuit measurements). Thermal waves were detected by means of the laser beam deflection technique which allows the contactless measurement of the oscillatory surface temperature of a sample with respect to amplitude and phase. A critical discussion of methods shows that the thermal diffusivity is most reliably determined by transmission experiments. From experimental data obtained by this method a mean value alpha = (2.8 +/- 0.9) x 10(-4) cm2 s-1 was evaluated for the thermal diffusivity of dry epidermis. PMID- 1741426 TI - Concentration dependence of fluorine impurity spin-lattice relaxation rate in bone mineral. AB - The concentration dependence of the fluoride ion spin-lattice relaxation rate has been observed by nuclear magnetic resonance experiments on samples of defatted and dried bone. The 19F spin-lattice relaxation rates increased linearly with the bone fluoride concentration. Different results were obtained from trabecular than from cortical bone. For the same macroscopic fluoride content per gram of bone calcium, the relaxation rate is significantly faster in cortical bone. Relaxation rates in cortical bone samples prepared from both rats and dogs were apparently controlled by the same species-independent processes. For samples from beagle dogs, the bulk fluoride concentrations measured by neutron activation analysis were 3.1 +/- 0.3 times greater in trabecular bone than in the corresponding cortical bone. The beagle spin-lattice relaxation data suggest that the microscopic fluoride concentrations in bone mineral were 1.8 +/- 0.4 times greater in trabecular bone than in cortical bone. It is concluded that the accumulation of fluoride impurities in bone mineral is non-uniform. PMID- 1741427 TI - Calculation of dose and contrast for two mammographic grids. AB - To aid in selecting optimal conditions for screening mammography practice in Sweden, the performance of two mammographic grids (one moving and one stationary) has been investigated. Monte Carlo techniques were used to simulate photon transport in the breast. Transport through the breast support, grid covers, grid and image receptor (33.9 mg cm-2 Gd2O2S) was treated analytically. The contrast of a 100 microns calcification has been evaluated for three tissue compositions (adipose, glandular, 50:50 fractions by weight of adipose and glandular tissue) as a function of breast thickness (2-8 cm) and potential difference (25-30 kV, Mo anode). Contrast for a 5 cm 'average' breast at 28 kV was improved by 40% using the moving grid and by 30% using the stationary one; the corresponding increases in breast absorbed dose, keeping the energy imparted to the image receptor constant, were 90% and 150%, respectively. The superior properties of the moving grid were due to (i) equal scatter rejection ability and higher transmission of primary photons yielding lower scatter-to-primary ratios behind the grid, and (ii) less attenuation and filtering of the primary photons in the interspace material yielding lower degradation of primary contrast. PMID- 1741428 TI - Optimization and evaluation of landmark-based image correlation. AB - Image correlation methods enable the complementary use of information from different medical images of a patient. These images can be obtained from different imaging devices (CT, MR, PET), or, from one imaging device taken at different times. Unfortunately, there are few cases in which the requirements for later image correlation are taken into account at the time of image acquisition. There is therefore a need for correlation techniques requiring no preparation in advance. We have developed two correlation methods, both based on three or more anatomical or artificial landmarks, to be defined in corresponding image data sets. These methods have been evaluated with phantom data as well as with patient data. We have improved these correlation methods by using more landmarks and special selection criteria. They are applicable to all medical tomograms and to x ray pictures taken under stereotactical conditions. The results obtained have error ranges in the order of the three-dimensional image resolution. PMID- 1741429 TI - Evaluation of imaging properties of a laser film digitizer. AB - In this paper we provide a quantitative assessment of the basic imaging properties of a laser film digitizer. The characteristic curve of the digitizer was determined in terms of the relationship between input optical density and output pixel value. Spatial resolution of the laser digitizer was characterized using the presampling modulation transfer function (MTF), which was measured using a curve fitting technique with an angulated slit. For the noise analysis, we compared the Wiener spectra of uniformly exposed film samples before and after digitization. The effects of different sampling distances and scanning directions were investigated. Our results show that the characteristic curve of the laser digitizer was linear. The presampling MTFs of the digitizer were similar at different sampling distances and were substantially greater in the vertical scanning direction than in the horizontal direction. The noise of the digitized film sample was mainly affected by the presampling MTF and structure noise of the digitizer. PMID- 1741430 TI - A single-shot shimming sequence using low-power RF noise pulses for localized in vivo NMR spectroscopy. PMID- 1741431 TI - Evaluation of ferromagnetic materials for low-frequency hysteresis heating of tumours. PMID- 1741432 TI - Constrained least-squares restoration and renogram deconvolution: a comparison by simulation. AB - Before deconvolution can be used in renography, it is necessary to decide whether the renal function is sufficiently good to allow it. To see if this decision can be circumvented, an iterative constrained least-squares restoration (CLSR) method was implemented in which the point of termination of the iteration occurs when a residual vector has a value less than an estimate of the noise in the original renogram curve. The technique was compared with the matrix algorithm and with direct FFT division. The comparison was achieved by deconvolving simulated renogram data with differing transit time spectra and statistics. As expected, the FFT technique produced results of little value whereas the CLSR and matrix methods produced values of mean transit time (MTT) that differed slightly from the expected results. Analysis indicated that the matrix approach was superior when the percentage noise component was less than 6% and vice versa. No technique produced useful transit time spectra. As the CLSR technique produced better results than the matrix method in simulations with relatively long MTTs and high noise, it seems reasonable to suggest that it might be used for renogram deconvolution without the need for previous inspection of the curves. PMID- 1741433 TI - Early-onset repeated dieting reduces food intake and body weight but not adiposity in dietary-obese female rats. AB - As dieting behavior and attempts at weight loss are becoming increasingly common in adolescent girls, we wished to determine whether early-onset repeated dieting influenced the development of obesity and its metabolic correlates. Female rats were fed a high-fat diet and subjected to six cycles of dieting and regain, beginning in the peripubertal period. Although dieted rats weighted less than nondieted high-fat fed controls at the completion of the sixth cycle, body composition analysis revealed that the two groups were equally obese. Cumulative caloric intake was less in dieted rats, suggesting that the pattern of consumption promoted by dieting helped to establish the obesity. Resting metabolic rate did not differ between the two groups. These data suggest that although early-onset repeated dieting may result in reduced body weight, the eventual level of adiposity may be unknowingly elevated, potentially leading to long-term health risks. PMID- 1741434 TI - Effects of prenatal testosterone and ATD on reproductive behavior in guinea pigs. AB - Most sexual dimorphisms in reproductive behavior are hormonally organized in the guinea pig. The study sought to determine whether the sexually dimorphic requirement for the aromatization of testosterone in the activation of mounting is organized by testosterone prenatally and whether aromatization of testosterone contributes to the organization of mounting behavior. Pregnant females were treated with testosterone, the aromatase inhibitor ATD, or vehicle from days 28 65 of gestation. The offspring were gonadectomized and tested as adults for lordosis and androgen-activated mounting behavior. Prenatal testosterone treatments altered the hormonal requirements for androgen-activated mounting in females such that they resembled normal males, and did not require aromatization as adults. Prenatal inhibition of aromatase activity decreased mounting activity in females but not in males. This treatment had no influence on lordosis in either sex. The results support the hypothesis that the same hormones that activate mounting behavior in the adult guinea pig are responsible for the organization of mounting behavior. PMID- 1741435 TI - Seminal vesicle and preputial gland response to steroids in adult male mice is influenced by prior intrauterine position. AB - There are differences in serum steroid concentrations during fetal life between male mice that develop between two male fetuses (2M males, with elevated testosterone) and between two female fetuses (0M males, with elevated estradiol). The present studies were undertaken to determine whether prior intrauterine position would influence the weight of seminal vesicles and preputial glands in adult male mice. To eliminate any potential differences between 2M and 0M males in circulating gonadal steroids, all males were castrated in adulthood and implanted with silastic capsules containing testosterone (T), dihydrotestosterone (DHT) or a combination of T and estradiol-17 beta (E2) or DHT and E2. Three weeks later, preputial glands were significantly heavier in 2M than 0M males after treatment with T but not DHT. Seminal vesicles were also significantly heavier (blotted wet weight) in 2M than 0M males after treatment with T. For 2M males, seminal vesicles weighed the same in response to treatment with T or DHT. However, relative to the effect of T, DHT significantly increased seminal vesicle weight in 0M males such that they were equivalent to weights in 2M males treated with T or DHT. This finding suggests that seminal vesicles in 0M males have lower concentrations of 5 alpha-reductase and, thus, a lower capacity to metabolize T to DHT which is required for normal seminal vesicle function. There were no significant effects of E2 (in combination with T or DHT) on seminal vesicle or preputial gland weight. PMID- 1741436 TI - Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations. AB - A discrete-trial current-threshold intracranial self-stimulation (ICSS) paradigm has been used extensively to examine the effects of drugs on reward thresholds. However, there is little work to date validating that this specific procedure measures reward. The purpose of the present study was to establish the construct validity of this procedure by testing the procedure's ability to measure reward effects and to discriminate these reward effects from performance effects. The discrete-trial ICSS procedure provides four measures: current thresholds, response latency, extra responses and time-out responses. The effects of a performance manipulation (variations in the force required to operate the manipulandum) and of a reward manipulation (variations in the train duration of the electrical stimulation) were evaluated on the four measures. Reward effects were reflected primarily in changes in thresholds, with no effect on any of the other three measures. Conversely, performance effects were reflected primarily in changes in response latency, extra responses and time-out responses, with only a small effect on thresholds. Finally, the paradigm's potential as a useful tool in the elucidation of the neurobiological basis of reward was demonstrated by investigating the effects of two pharmacological agents, cocaine and curare, on the four measures derived from the discrete-trial current-threshold ICSS procedure. The results suggest that the discrete-trial current-threshold procedure can readily discriminate reward from performance treatments. PMID- 1741437 TI - The amount eaten in meals by humans is a power function of the number of people present. AB - The influence of social factors on the eating behaviors of humans was investigated by paying 153 adults to maintain 7-day diaries of everything they ingested and the number of other people present. Over 3800 meals were separated according to the number of other people present at the meal. Meal size, macronutrient composition, and the deprivation ratio was found to increase while the satiety ratio decreased as a function of the number of people present in a fashion best described by a power function. Meal duration and the rate of intake were best described as linear functions of the number of people present. Meals eaten in large groups were over 75% larger than when eaten alone. The findings suggest that social facilitation of naturally occurring meal intake by humans is an extremely potent influence on intake that is an instance of a very general phenomenon governing many forms of behavior. PMID- 1741438 TI - The involvement of glucocorticoids in the acquired immobility response is dependent on the water temperature. AB - The Porsolt swim test was used to study the role of glucocorticoids in a simple learning paradigm. Two experiments were performed. In the first experiment, the stressfulness of the situation was manipulated by testing control, sham-operated and adrenalectomized mice at different water temperatures (20 degrees C, 25 degrees C, 30 degrees C and 35 degrees C). In the second experiment, control mice were injected with the glucocorticoid antagonist RU38486 (3.2 mg/kg, 10 mg/kg, 32 mg/kg); adrenalectomized mice were injected with the glucocorticoid agonists corticosterone (0.46 mg/kg, 1.0 mg/kg, 2.2 mg/kg) and dexamethasone (0.005 mg/kg, 0.05 mg/kg, 0.1 mg/kg). The results show that water temperature is a very important factor in the Porsolt swim test. It influences the overall behaviour of the animals and changes the involvement of glucocorticoids. At a water temperature of 25 degrees C, glucocorticoids play an important role in the retention of the immobility response; ADX mice are impaired, and this impairment can be ameliorated by corticosterone and dexamethasone injection. Furthermore, the impairment can be induced in control mice by RU38486. The effects observed at 25 degrees C were, however, not observable at 20 degrees C, 30 degrees C and 35 degrees C, which suggests, contrary to previous reports, that glucocorticoids do not play a universal role in retention processes. PMID- 1741439 TI - Effects of habitual caffeine use and acute ingestion: testing a biobehavioral model. AB - A recently proposed model of the biobehavioral effects of caffeine suggests that acute ingestion impacts physiology and behavior differentially depending on the level of habitual usage of the drug. Acute ingestion and habitual usage are particularly expected to affect arousal and attentional processes. Subjects in the present study were preselected for high and low habitual caffeine use, given caffeine or a placebo, exposed to white noise or no white noise, and asked to perform on several tasks. Included were an arousal/habituation task (pure tones), reaction time, paired associates, anagrams, and vigilance. Electrodermal activity and performance were recorded. As predicted, virtually all effects were on the arousal/habituation and attentional (vigilance) tasks. Both acute ingestion and habitual use increased tonic EDA, and chronic use also reduced phasic responding, especially in the presence of a strong habituating stimulus. Both acute and habitual use also liberalized the vigilance response criterion, in that subjects risked more false alarms in order to attain more hits. In addition, habitual use increased sensitivity and reduced accuracy, and acute ingestion increased vigilance response time in the presence of white noise. Overall, the model was partially supported by these early results, though considerable further research is needed. PMID- 1741440 TI - Ingestive/aversive response of rats to sweet stimuli. Influence of glucose, oil, and casein hydrolyzate gastric loads. AB - Facial consummatory responses reflecting ingestive and aversive perceptions were studied and quantified in rats chronically implanted with gastric and oral catheters. A gustatory stimulus of 50 microliters of 0.6 mol.l-1 sucrose was injected into the mouth every 5 min during 90 min. At time zero, one of seven loads was injected into the stomach. These consisted of, 5 ml of water, or 5 ml solution containing 1 g glucose, 3 g glucose, 1 g casein hydrolyzate, 3 g casein hydrolyzate, or of oil 0.6 ml, or 1.4 ml. The typical ingestive facial consummatory responses in response to sweet stimuli were observed prior to all gastric loads, and also after the water load. On the other hand, the consummatory responses to sweet stimuli turned aversive after all three high-calorie gastric loads. The magnitude of this decrease in palatability (negative alliesthesia) was similar after glucose, casein hydrolyzate, and oil. The reversal of the consummatory responses from ingestive to aversive did not reach the threshold of statistical significance after the three low-calorie gastric loads. These results would tend to show that the intestinal signal for alimentary alliesthesia is nonspecific. PMID- 1741441 TI - Reinforced variability in rats: effects of gender, age and contingency. AB - Operant variability was compared in four groups of Long-Evans rats (young males, young females, mature males and mature females) under two different conditions. Under VAR contingencies, where response variability was required for reinforcement, a sequence of four responses on left (L) and right (R) levers had to differ from each of the preceding four sequences. If LLLL, LRLL, RRRR, and RRLL had just occurred, then a RLRL sequence, for example, would be reinforced in the next trial, but LRLL would not. Sequence variability was compared to that under YOKE contingencies, where reinforcement was provided whether or not the rats varied their responses. We found that young rats behaved more variably than mature rats, this effect most pronounced under the YOKE contingencies, where variability was not required. On the other hand, variability was not related to gender under either VAR or YOKE conditions. Thirdly, all groups were sensitive to the schedule contingencies, behaving more variably under VAR than under YOKE. Thus age and schedule requirements influenced operant variability, but gender did not. PMID- 1741442 TI - Physiological effects of dieting and bingeing in rats. AB - Female rats were assigned to dietary conditions as follows for 3.5 months: 1) Low fat control (LFC); 2) Moderately high-fat control (HFC); 3) Alternation between restricted access to a low-fat diet and ad lib access to a very high fat diet (RA); 4) Unrestricted access to the same diets as RA (URA). Results indicate that: 1) HFC consumed the same energy as LFC, but showed a tendency to become heavier and fatter through greater food efficiency. 2) URA and LFC did not differ in body weight, food intake, body composition or energy efficiency. 3) Intake of the very high fat diet declined over time in the RA. 4) RA ate less total calories, weighed less than all other groups, and showed a tendency for decreased percentage body fat and increased percentage of weight gained due to FFM gained. Results provide no evidence that dieting and bingeing promote obesity or increased preference for dietary fat, and suggest that dietary restriction has greater impact on energy balance and body composition than does alternation of diet composition. PMID- 1741443 TI - Restricted feeding: a nonphotic zeitgeber in the rabbit. AB - The free-running circadian rhythms of five behavioral functions of the rabbit were masked by unsignalled restricted food access (RF). The rhythms were reorganized immediately, a large part of events being assembled around the end of food availability. In addition to masking a slower process of entrainment was running: a component of anticipatory activity (AA) was established 1-3 h before food access. AA consolidated in continuation of the camouflaged free-running rhythm. The time of AA establishment correlated significantly with the phase angle difference (PAD) between free-running rhythm and RF: it decreased with decreasing positive PAD. With the consolidation of AA, the rhythms had attained a stable phase relation to RF. At the termination of RF, the circadian rhythms started to free-run again, the phase being dependent from that of the preceding RF schedule. The period length of the RF zeitgeber (TRF) had some impact on tau of the circadian rhythm. This aftereffect was most evident after termination of TRF less than 24 h: the free-running rhythm continued for up to 49 days with a tau less than 24 h and turned longer thereafter. The results demonstrate the entrainment of circadian rhythms of the rabbit by RF in addition to masking. PMID- 1741444 TI - Circadian effects of escapable and inescapable shock on the food intake and wheelrunning of rats. AB - The feeding and running activities of rats were used to characterize the stressful effects of footshock. A 12-hour light/dark cycle was continuously in effect. During the preshock stage, all rats lived in individual cages where they could drink water, press a lever once for each 45 mg food pellet or run in an attached running wheel. During the shock stage, rats were moved to cages where they could drink and eat, but not run. Five s of light followed by 5 s of a light + tone compound preceded five progressively more intense shock levels. Rats in group AE were trained to pull a ceiling chain to avoid/escape from footshocks that were scheduled 24 hours per day. In group YS, the frequency, intensity and pattern of shocks for a rat were yoked to a rat in group AE. Rats in group CN were not shocked. During recovery, rats were allowed to resume running. During the dark, but not the light of the first day of shock, the intake of groups AE and YS was less than the intake of group CN. By the third day of shock, the food intake of group AE recovered and was no longer different from the intake of group CN. Intake of group YS remained less than the intakes of groups AE and CN during the remainder of the shock stage. When shock was terminated, the intake of the YS group recovered, but neither running nor food intake differed among groups. These results suggest that although inescapable shock disrupts food intake more than escapable shock, this disruption is specific to the duration of the shock stage and depends on rat's circadian pattern of intake. PMID- 1741445 TI - Lesions of the central nucleus of the amygdala block the excitatory effects of septal ablation on the acoustic startle reflex. AB - Many studies have investigated the role of the septum and the amygdala in emotional behavior. While the literature is somewhat inconsistent, most studies suggest a role for the septal nuclei in the inhibition of fear and stress responses (at the behavioral, autonomic and hormonal levels) while the central nucleus of the amygdala is involved in the production of such responses. The present study examined the ability of lesions of the central nucleus of the amygdala to block the excitatory effects of complete septal ablation on the acoustic startle reflex. Septal ablation produced a significant increase in startle amplitude which was blocked by concomitant lesions of the central nucleus of the amygdala. These results suggest that the increase in startle amplitude resulting from septal damage might be due to a disinhibition of neuronal activity in the central nucleus of the amygdala, a structure known to mediate the increase in startle associated with conditioned and unconditioned fear, or from antagonistic interactions at other target sites which themselves modulate startle. PMID- 1741446 TI - Lordosis in male rats: the facilitatory effect of mesencephalic dorsal raphe nucleus lesion. AB - The dorsal raphe nucleus was destroyed (DRL) by a radiofrequency lesion generator in castrated male rats, and lordosis behavior was observed. Five weeks after the surgery, all animals were implanted with two Silastic tubes containing estradiol (E2). Behavioral tests were started 2 days after implantation of E2 and carried out every other day for 16 days. Castrated control and sham-operated control males showed low incidence of lordosis and low lordosis quotient (LQ) throughout the tests, whereas all the DRL males displayed lordosis and the mean LQ of the group was significantly higher than that of control groups, but lower than that of an ovariectomized female group. These results suggested that the dorsal raphe nucleus plays an important role in inhibiting lordosis in male rat brain. PMID- 1741447 TI - Rat circadian rhythms entrain to a descending saw-tooth light intensity cycle. AB - We reexamined whether rat circadian rhythms entrained to the light intensity cycle of a descending saw-tooth (ST-d) form, in which illuminance decreased rectilinearly from 300 lx to 0 lx in 24 h, and abruptly returned to 300 lx (lights-on time). Ambulation, drinking and subcutaneous body temperature were simultaneously monitored in 5 intact, 5 pinealectomized and 5 orchiectomized rats. Additionally, sleep was monitored in the intact rats. In all the rats, entrainment was confirmed during 65 days' exposure to the ST-d cycle. The waveforms of the entrained rhythms were much modified compared with those during LD 12:12. The estimated activity periods of the entrained rhythms straddled the lights-on time of the ST-d cycle. In all the groups of rats, administration of a single ST-d cycle in constant dim red light produced only delay shifts irrespective of its circadian phase, and there was no significant circadian variation in the magnitude of phase shifts. The results indicate that rat circadian rhythms entrain to the ST-d cycle with an unexpected phase position, which cannot be explained by the phase-response curve. PMID- 1741448 TI - Air puff versus shock unconditioned stimuli in rabbit heart rate conditioning. AB - The present study examined whether corneal air puff can be used as an unconditioned stimulus to elicit reliable classically conditioned heart rate (HR) responses in rabbits. The conditioned and unconditioned HR responses were assessed during Pavlovian conditioning with different intensities of paraorbital shock (2.7, 1.2, or 0.5 mA) or corneal air puff (18.3, 5.9, or 2.2 N/cm2) unconditioned stimuli (UCSs). Each experimental group was given one acquisition session during which an acoustic conditioned stimulus was paired with either the high, medium, or low intensity of a shock or air puff UCS. The results suggest that: a) HR is reliably conditioned with a high-intensity air puff UCS, and with medium- or high-intensity paraorbital shock stimuli; and b) only UCSs that elicit a tachycardiac unconditioned HR response reliably support HR conditioning. It was concluded that either air puff or paraorbital shock can serve as an effective UCS for HR conditioned responses. PMID- 1741449 TI - Thirst and salt appetite induced by hypovolemia in rats: analysis of drinking behavior. AB - A detailed description of the increased intake of water and 0.5 M NaCl solution by rats after colloid-induced hypovolemia was obtained by measuring drinking activity every 6 s for 23 h. After an initial phase of largely single-bout water drinking that reflected hypovolemic thirst, there was a marked increase in saline drinking in multiple-bout episodes. This salt appetite developed while rats were volume depleted but persisted for hours even after the plasma volume deficits were repaired. Their drinking episodes then seemed to reflect osmoregulation, since cumulative intakes of water and saline were in appropriate proportions to produce a near-isotonic NaCl solution. Remarkably, rats concocted a 1% NaCl solution within 29% of the drinking episodes, by alternating intakes of water and saline every 30-90 s. This alternation was too rapid to allow significant absorption of ingested fluids from the intestines and changes in plasma osmolality, and thereby to permit central osmoreceptors to influence ongoing consumption. Instead, we propose that, in these episodes, rats are guided by gustatory receptors to obtain the desired NaCl in a palatable solution. PMID- 1741450 TI - Clozapine: strong antiaggressive effects with minimal motor impairment. AB - Clinical studies have shown clozapine to be effective in the treatment of schizophrenia and associated with an extremely low incidence of extrapiramidal side effects. Diverse studies indicate that clozapine is an atypical neuroleptic with a preferential activity on the mesolimbic structures and a lower affinity for striatal D2 receptors than the classical antipsychotics. The purpose of this study was to assess the behavioral properties of clozapine, especially its effects on aggressive and motor behaviors. Individually housed male mice of the OF1 strain were exposed to anosmic "standard opponents" 30 minutes after the last drug administration. One category of animals received a single IP dose of the compound (0.2, 0.5, 1 or 1.5 mg/kg). Another category received daily doses (0.5, 1 or 1.5 mg/kg) for 21 days. Encounters were videotaped and behavior evaluated using an ethologically based analysis. Clozapine, in the acute treatment condition, produced a significant decrease in "attack" and "threat" behaviors without "immobility" being significantly increased. These results suggest a rather specific antiaggressive action of the compound with little motor impairment. In the chronic administration, no significant change in aggressive behavior was observed which may be attributed to the development of some degree of tolerance. PMID- 1741451 TI - Chorda tympani and lingual nerve responses to astringent compounds in rodents. AB - A wide variety of compounds in foods and beverages produce astringent sensations when introduced into the oral cavity. There is controversy, however, whether "astringency," with its associated puckering and drying sensations, is a fundamental taste quality or is a tactile sensation. To address this issue, electrophysiological recordings were made from the gerbil chorda tympani nerve and the rat lingual nerve. The chorda tympani nerve transmits taste information from the anterior 2/3 of the tongue, whereas the lingual nerve transmits tactile, thermal and pain sensations from the anterior 2/3 of the tongue. The astringent compounds tested were: tannic acid, tartaric acid, gallic acid, aluminum ammonium sulfate and aluminum potassium sulfate. Tannic acid, tartaric acid, and gallic acids were tested at concentrations up to 120 mM over a pH range from approximately 2 to 6. The aluminum salts were tested at concentrations up to 160 mM only at low pH's. All compounds rapidly (and at lower concentrations, reversibly) stimulate the chorda tympani nerve in a concentration-dependent manner at all pH's tested. The rapidity and reversibility of the chorda tympani responses suggest that astringent-tasting compounds interact directly with taste cells rather than indirectly by precipitating salivary proteins. At pH 6, tannic acid, tartaric acid, and gallic acid all elicit robust chorda tympani responses, implying that the ionized forms of these compounds produce taste sensations. None of these compounds stimulate lingual nerves over the same concentration and pH ranges used in the chorda tympani experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741452 TI - Differential effects of neonatal testosterone treatment on aggression in two selection lines of mice. AB - Selection lines of mice, artificially selected for aggression based upon the attack latency score (ALS), were used. In order to determine the relative contribution of neonatal testosterone (T) in the development of aggression, we vary the plasma-T level in males of both selection lines on the day of birth. At 14 weeks the ALS was measured. Neonatal T treatment results in a reduction of aggression in the long attack latency (LAL) line, whereas aggressive behaviour of the short attack latency (SAL) line is not affected. Both selection lines show reduction in testicular weight, although the total amount of T-producing Leydig cells was not affected. Neonatal T may cause a permanent reduction in aggressive behaviour in in the LAL line only, probably due to differential appearance of critical periods. It is suggested that the difference in aggressive behaviour between SAL and LAL selection lines is due to a prenatally determined difference in neonatal T sensitivity of the brain. PMID- 1741453 TI - Age-related changes in spontaneous behavior and learning in NMRI mice from middle to old age. AB - Spontaneous behavior, sensorimotor reflexes and learning of 3-, 11-, 17- and 22 month-old virgin female NMRI mice were compared. Sensorimotor abilities decreased significantly from the age of 17 months in proportion to the muscular and equilibrium demand of the test. Open-field activity, hole board exploration as well as activity in the Y maze and plus maze decreased from the age of 11 months. However, in the open-field and Y maze, it was not possible to distinguish between 11-, 17- and 22-month-old mice, whereas in the plus maze, activity was drastically decreased in 17- and 22-month-old mice. In the plus maze, indices of fear-motivated behavior suggest a greater sensitivity to the situation in the age groups of 17 and 22 months. Spontaneous alternation also decreased from the age of 11 months, but at the age of 22 months, a rotational behavior emerged. Spatial learning was markedly impaired from middle age, i.e., 11 months, as indicated by longer latencies and absence of spatial bias in place learning. In cued learning, the 11- and 17-month groups eventually reached the level of the 3-month-old mice, while the 22-month age group remained impaired. Changes in swimming ability or speed did not appear to account for the swimming maze deficits. In contrast, a sensory or perceptual deficit cannot be excluded for the oldest mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741454 TI - The threshold for satiating effectiveness of psyllium in a nutrient base. AB - A combination of psyllium fiber with nutrients in a commercially available wafer (Fiberall-Ciba Consumer Pharmaceutical) was evaluated for its effectiveness in reducing food intake and appetite. Each of 15 nonobese healthy women received no wafers and four different amounts (39, 104, 169, and 234 kcal) of the fiber wafer with water, in a ratio of 13 kcal (and 0.565 g psyllium) wafer per 41.67 g water, 30 minutes prior to a test meal of macaroni and beef, on nonconsecutive days. Intake of the test meal and hunger ratings were both significantly reduced after intake of the two largest wafer amounts (169 and 234 kcal, respectively), in comparison with the two smaller amounts and none at all. The reduction produced by the largest amount compared to none at all was 122 kcal (about half the energy of the amount given). There were no significant differences in intake and hunger ratings among the two smaller amounts and none at all. Thus the threshold for intake reduction by this product with water lies between 104 and 169 kcal. Methodologically, this work underscores the importance of testing the satiating effects of foods at multiple levels before conclusions are drawn about their satiating effectiveness, and suggests that the threshold for significant reduction should be considered as a measure of the product's satiating effectiveness. The relative contributions of the nutrients, the fiber, and the water to the satiating effect still need to be determined. PMID- 1741455 TI - Handling elevates the colonic temperature of mice. AB - Handling mice for repeatedly measuring their colonic temperature (Tc) resulted in a significant rise in their Tc. When the procedure was repeated day after day, this response diminished by habituation, showing the emotional origin of Tc rise. Salicylate lowered both the maximal Tc reached during handling and the Tc before handling without affecting the difference between the initial and the maximal Tc. During the first Tc measurement in a session, concomitant to the Tc rise, ear pinna temperature decreased. When Tc reached a plateau during the last measurements, ear temperature increased. This vasomotor response suggests that stress Tc rise is a regulated Tc change. However, since, contrary to what was reported in the rat, the salicylate did not diminish the magnitude of the Tc rise, it is doubtful that the emotional Tc rise in mice is a true fever. PMID- 1741456 TI - Mechanism of reproductive deficiency in spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) show multiple endocrine disorders. In the present work, specific reproductive modifications were analysed using normotensive Wistar-Kyoto rats (WKY) as controls. SHR showed delayed vaginal opening and first estrus presentation, regular vaginal cycles and released a normal number of ova each cycle. When compared with controls, SHR showed a decrease in the percentage of successful pregnancies (69% vs. 86% in WKY) and in the litter size (7.83 +/- 0.5 vs. 10.41 +/- 0.5). In SHR, progesterone plasma levels were significantly increased during the days 1-14 of pregnancy, and on the 5th day of pregnancy the plasma concentrations of LH but not of FSH were enhanced. Mortality during the first month of life was higher in SH (50%) than in control (24%) strain. When the SH females were mated with Wistar or WKY males, the percentage of pregnancies rose up to 95%. On the contrary, Wistar or WKY females mated with SH males showed a decrease in the percentage of pregnancies (62.5% and 50%, respectively). Besides, the litter sizes were significantly reduced in Wistar females mated with SH males. Newborn SH suckled immediately after birth from a WKY mother showed a significant reduction in the mortality during the first month of life (8% vs. 50%). In conclusion, our results suggest that changes in fertilization and/or implantation processes of SH rats were responsible for the reduced pregnancy rate, whereas the increased neonatal mortality could be due to lactation activity of SH mothers. PMID- 1741457 TI - Plasmid-determined metal resistance mechanisms: range and overview. PMID- 1741458 TI - Resistance to cadmium, cobalt, zinc, and nickel in microbes. AB - The divalent cations of cobalt, zinc, and nickel are essential nutrients for bacteria, required as trace elements at nanomolar concentrations. However, at micro- or millimolar concentrations, Co2+, Zn2+, and Ni2+ (and "bad ions" without nutritional roles such as Cd2+) are toxic. These cations are transported into the cell by constitutively expressed divalent cation uptake systems of broad specificity, i.e., basically Mg2+ transport systems. Therefore, in case of a heavy metal stress, uptake of the toxic ions cannot be reduced by a simple down regulation of the transport activity. As a response to the resulting metal toxicity, metal resistance determinants evolved which are mostly plasmid-encoded in bacteria. In contrast to that of the cation Hg2+, chemical reduction of Co2+, Zn2+, Ni2+, and Cd2+ by the cell is not possible or sensible. Therefore, other than mutations limiting the ion range of the uptake system, only two basic mechanisms of resistance to these ions are possible (and were developed by evolution): intracellular complexation of the toxic metal ion is mainly used in eucaryotes; the cadmium-binding components are phytochelatins in plant and yeast cells and metallothioneins in animals, plants, and yeasts. In contrast, reduced accumulation based on an active efflux of the cation is the primary mechanism developed in procaryotes and perhaps in Saccharomyces cerevisiae. All bacterial cation efflux systems characterized to date are plasmid-encoded and inducible but differ in energy-coupling and in the number and types of proteins involved in metal transport and in regulation. In the gram-positive multiple-metal-resistant bacterium Staphylococcus aureus, Cd2+ (and probably Zn2+) efflux is catalyzed by the membrane-bound CadA protein, a P-type ATPase. However, a second protein (CadC) is required for full resistance and a third one (CadR) is hypothesized for regulation of the resistance determinant. The czc determinant from the gram negative multiple-metal-resistant bacterium Alcaligenes eutrophus encodes proteins required for Co2+, Zn2+, and Cd2+ efflux (CzcA, CzcB, and CzcC) and regulation of the czc determinant (CzcD). In the current working model CzcA works as a cation-proton antiporter, CzcB as a cation-binding subunit, and CzcC as a modifier protein required to change the substrate specificity of the system from Zn2+ only to Co2+, Zn2+, and Cd2+. PMID- 1741459 TI - Copper resistance determinants in bacteria. AB - Copper is an essential trace element that is utilized in a number of oxygenases and electron transport proteins, but it is also a highly toxic heavy metal, against which all organisms must protect themselves. Known bacterial determinants of copper resistance are plasmid-encoded. The mechanisms which confer resistance must be integrated with the normal metabolism of copper. Different bacteria have adopted diverse strategies for copper resistance, and this review outlines what is known about bacterial copper resistance mechanisms and their genetic regulation. PMID- 1741460 TI - Plasmid-mediated resistance to tellurite: expressed and cryptic. AB - The ability of some bacteria to grow in the presence of high concentrations of tellurium compounds has been recognized for almost 100 years. Since then, interest in this phenomenon has generated a slow but steady trickle of literature. In the past few years, the use of modern techniques in molecular biology has led to a dramatic increase in our understanding of the genetics of several bacterial determinants for resistance to tellurium compounds. These determinants are frequently found to be encoded by plasmids which carry multiple antibiotic resistance determinants. Our understanding of the biochemistry of these systems remains limited. In this article, the history of the study of bacterial resistance to tellurium compounds is briefly reviewed. This is followed by an analysis of the recent developments in the study of plasmid-mediated resistance determinants. Finally, preliminary investigations on the possible mechanisms of bacterial resistance to tellurium compounds are presented. PMID- 1741461 TI - Plasmid chromate resistance and chromate reduction. AB - Compounds of hexavalent chromium (chromates and dichromates) are highly toxic. Plasmid genetic determinants for chromate resistance have been described in several bacterial genera, most notably in Pseudomonas. Resistance to chromate is associated with decreased chromate transport by the resistant cells. The genes for a hydrophobic polypeptide, ChrA, were identified in chromate resistance plasmids of Pseudomonas aeruginosa and Alcaligenes eutrophus. ChrA is postulated to be responsible for the outward membrane translocation of chromate anions. Widespread bacterial reduction of hexavalent chromate to the less toxic trivalent chromic ions is also known. Chromate reduction determinants have not, however, been found on bacterial plasmids or transposons. In different bacteria, chromate reduction is either an aerobic or an anaerobic process (but not both) and is carried out either by soluble proteins or by cell membranes. Chromate reduction may also be a mechanism of resistance to chromate, but this has not been unequivocally shown. PMID- 1741462 TI - Germanium and silver resistance, accumulation, and toxicity in microorganisms. AB - Germanium is an inert metal with no known biological function in prokaryotic or eukaryotic organisms. Its toxicity is low compared to that of silver. Germanium is accumulated in certain bacterial strains by either energy-independent passive binding or an energy-dependent mechanism. Little is known about the molecular aspects of silver resistance, toxicity, and accumulation in bacterial strains. This is surprising because silver has been used as an antimicrobial agent in the medical field for centuries. It is likely that silver ions are excluded (resulting in decreased silver accumulation) from certain bacterial strains or immobilized intracellularly to prevent toxic effects from being exerted. These mechanisms of silver resistance have not been fully elucidated. This review examines the toxicity and accumulation of germanium and silver in selected microbial species. In addition, resistance mechanisms to these biologically nonessential metals is discussed, with more emphasis placed on silver-resistant bacteria due to the knowledge available. PMID- 1741463 TI - An anatomic review of the delay phenomenon: I. Experimental studies. AB - A number of experiments were conducted to study the anatomic changes in a flap following a surgical delay using the Doppler probe to add precision to the technique. After scanning the integument of a series of anesthetized animals with the probe, each was sacrificed; a total-body arterial injection was performed with a lead oxide mixture, the integument and deep tissues were radiographed separately, and the results were correlated and compared with our previous human studies. The dog was selected from the range of animals examined, and the arterial networks of a number of skin and muscle flaps were studied with and without a surgical delay. The study included the use of a tissue expander. Results revealed that an adjacent cutaneous perforator could be captured with safety on the artery at the base of an undelayed flap; that the survival length of that flap was related to the distance between perforators; that the necrosis line of the flap usually appeared in the zone of choke vessels connecting adjacent territories; that a surgical delay results in a dilatation of existing vessels with maximal effect in the zone of choke arteries; that the most effective delay was obtained by elevating the flap in stages from the base, leaving detachment of the tip until last; that tissue expansion is a form of surgical delay, with particular emphasis on vessel hypertrophy; and that similar changes occur when a muscle is delayed. The clinical applications of this investigation are presented in Part II of this anatomic review of the delay phenomenon. PMID- 1741464 TI - An anatomic review of the delay phenomenon: II. Clinical applications. AB - This paper applies the anatomic concepts and data obtained from our animal experimental studies of the delay phenomenon to a series of clinical cases. Similar clinical results were obtained to those seen in Part I of our study when skin flaps were raised with and without a delay, when a tissue expander was used, and when the delay technique was extended to musculocutaneous flaps. In each instance, the cutaneous perforators were identified with the Doppler probe to facilitate the delay of specific vessels rather than dividing those at random. Intraoperative arteriograms and venograms reveal that the choke arteries dilate and the anatomically unfavorable valved vein segments become regurgitant. The end result is the observation that at least one additional anatomic vascular territory can be added to the length of a flap with safety following a surgical delay. PMID- 1741465 TI - Results of multidisciplinary management of bilateral cleft lip and palate at the Iowa Cleft Palate Center. AB - Bilateral cleft of the lip and palate is by many standards the most complex and severe form of the defect. The complexity and severity of the defect require an unusual degree of cooperation among all specialists and especially between the surgeon and the orthodontist. There are no published findings that we know about in which comprehensive data from a number of disciplines are reported for the same group of bilateral cleft patients. Fifty randomly selected patients with bilateral complete clefts were examined by the Iowa team and two orthodontists from other institutions. The evaluations revealed that a large number of patients over the age of 10 have multiple residual problems requiring further treatment. Only 23 percent of the older patients studied were judged to have had treatment completed by the surgeon, speech pathologist, and orthodontist. It is very difficult to state whether the results obtained by our team can be considered satisfactory because there are no comparable studies that have attempted to evaluate the same parameters in multidisciplinary management. PMID- 1741466 TI - Gold eyelid weights in patients with facial palsy: a patient review. AB - Lid loading with gold weights inserted into a submuscular pocket in the upper eyelid is a useful, simple, and effective method for the treatment of lagophthalmos in patients with temporary or permanent facial nerve palsy. The incidence of complications in our series was high. The reason for this are discussed, and methods of reducing the rate of complications are suggested. PMID- 1741467 TI - The relationship of the superficial and deep facial fascias: relevance to rhytidectomy and aging. AB - Controversy persists regarding the relationship of the superficial facial fascia (SMAS) to the mimetic muscles, deep facial fascia, and underlying facial nerve branches. Using fresh cadaver dissection, and supplemented by several hundred intraoperative dissections, we studied facial soft-tissue anatomy. The facial soft-tissue architecture can be described as being arranged in a series of concentric layers: skin, subcutaneous fat, superficial fascia, mimetic muscle, deep facial fascia (parotidomasseteric fascia), and the plane containing the facial nerve, parotid duct, and buccal fat pad. The anatomic relationships existing within the facial soft-tissue layers are (1) the superficial facial fascia invests the superficially situated mimetic muscles (platysma, orbicularis oculi, and zygomaticus major and minor); (2) the deep facial fascia represents a continuation of the deep cervical fascia cephalad into the face, the importance of which lies in the fact that the facial nerve branches within the cheek lie deep to this deep fascial layer; and (3) two types of relationships exist between the superficial and deep facial fascias: In some regions of the face, these fascial planes are separated by an areolar plane, and in other regions of the face, the superficial and deep fascia are intimately adherent to one another through a series of dense fibrous attachments. The layers of the facial soft tissue are supported in normal anatomic position by a series of retaining ligaments that run from deep, fixed facial structures to the overlying dermis. Two types of retaining ligaments are noted as defined by their origin, either from bone or from other fixed structures within the face.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741468 TI - Frey's syndrome: a preventable phenomenon. AB - Gustatory sweating, or Frey's syndrome, is a fairly common sequela of partial or radical parotidectomy, submaxillary gland surgery, or radical neck dissection. It is caused by an anastomotic communication with facial sweat glands by parasympathetic secretomotor nerve fibers intended for the excised parotid gland; treatments, whether surgical or topical, generally have been less than satisfactory. We present the first documented prophylactic approach to Frey's syndrome that is performed during and as part of parotidectomy. The surgery involves use of the superficial aponeurotic system (SMAS) as an interposing flap to interrupt the anastomotic nerve communication with the sweat glands. The SMAS is derived from the fascia in the periauricular cheek and neck area that is continuous with the platysma muscle. In a prospective study in 55 patients undergoing elective parotidectomy, the SMAS flap was elevated during the beginning of the operative procedure once it had been determined that fashioning of the flap would in no way compromise tumor excision. In all cases, at follow up, there has been no clinical evidence of development of Frey's syndrome. We have shown that the development of the SMAS flap in parotid gland resections is an effective new approach both as a preventative measure against Frey's syndrome and as an aesthetic improvement over the usual defect typical of parotidectomies. PMID- 1741469 TI - Elimination of the vertical scar in reduction mammaplasty. AB - We describe a technique to eliminate the vertical portion of the inverted-T incision in patients who have combined enlargement of the breasts and moderate to severe ptosis. Initial preoperative markings are made, placing the new nipple site at the level of the transposed inframammary crease. The nipple-areola complex is then retained on a vascularized pedicle, with major reduction of the breast tissue being done in the medial and lateral quadrants. The nipple and breast tissue are then tucked underneath the superior skin segment and placed in this new position as one would do with the umbilicus in an abdominoplasty. Excess vertical skin is removed, and horizontal excess is collected at the midline as a small dog-ear. We have found that this dog-ear reduces markedly with time, rounding out the inferior portion of the breasts. The remaining small amount of excess skin can then be removed under local anesthetic at a later date. We have performed this procedure on 20 patients, with follow-up from 6 to 24 months. PMID- 1741470 TI - The free vastus lateralis flap: an anatomic study with case reports. AB - The suitability of the thigh as a donor site for a new free flap was examined in 100 cadavers. It was found that the vastus lateralis muscle can be used to form a myocutaneous or fasciomuscular flap, the raising of which causes no technical problems and leads to no functional and only minor aesthetic impairments. Depending on the muscle segment from which the flap is raised, a neurovascular pedicle measuring between 8 and 20 cm with a diameter of 2 to 2.5 mm (artery) or 2.5 to 4 mm (vein) can be formed. The skin island in the myocutaneous flap measures on average 8 x 16 cm and is located above the middle portion of the muscle. The diameter of the supplying perforator vessel is between 0.7 and 1.2 mm. The flap can be raised parallel to head and neck surgery and applied as a myocutaneous flap for coverage of extensive or perforating defects or intraorally as a fasciomuscular flap. PMID- 1741471 TI - Microvascular soft-tissue transplantation for reconstruction of acute open tibial fractures: timing of coverage and long-term functional results. AB - Seventy-two patients with Gustilo grade IIIB open tibial fractures were treated with free-tissue transfers. If successful free-tissue transfer for soft-tissue reconstruction is performed within 15 days of injury, the risk of major complications is 3.6 percent. Long-term retrospective follow-up (mean 42 months) revealed successful limb salvage in 93 percent, good aesthetic results in 80 percent, and patient satisfaction in 96 percent. However, 66 percent of patients exhibited significantly decreased range of motion of the ankle, 44 percent experienced swelling and edema requiring elastic support and activity modification, and 50 percent occasionally required an assistance device for ambulation. The long-term employment rate was 28 percent, and no patient returned to work after 2 years of unemployment. In contrast, 68 percent of amputees after lower extremity trauma over the same period returned to work within 2 years. Patients need to realize the disruptive nature of this injury on their family, job, and future. PMID- 1741472 TI - Tobacco smoking and complications in elective microsurgery. AB - This study assesses the risk for complications in patients who chronically smoke but who have quit in the perioperative period of an elective free-tissue transfer as compared with patients who do not smoke. A retrospective review identified 104 free-tissue transfers in 93 smokers and 58 transfers in 51 nonsmokers. The demographics, wound etiology, and recipient sites were similar in the two populations. With the exception of a higher incidence of chronic obstructive pulmonary disease (COPD) among smokers, preexisting comorbid factors also were similar. Postoperative medical complications were comparable between populations. When comparing smokers with nonsmokers, we found that anastomotic patency and flap survival were not different (95 versus 94 percent, respectively), that delayed wound healing at the recipient site was different (35 versus 24 percent), and that smokers require an additional procedure to achieve final wound closure more frequently (27 versus 12 percent, p = 0.03). These findings suggest that cigarette smokers are at increased risk for complications, not at the site of the anastomosis in free-tissue transfer, but rather at the flap's interface with the wound or overlying skin graft. PMID- 1741473 TI - Monitoring of free flaps with surface-temperature recordings: is it reliable? AB - Surface-temperature recording (STR) is one of the oldest and simplest methods of postoperative monitoring of free flaps. Its usefulness, however, remains poorly documented, and its problems, not well understood. To assess its value, we reviewed our series of 600 consecutive free flaps where surface-temperature recording was the main method of monitoring used and a detailed temperature record was kept. Seventy flaps suffered a postoperative microvascular compromise necessitating a surgical reexploration. Of these, 62 charts were satisfactory for review and were matched with 62 charts from similar but uncomplicated flaps. The derived value C delta T, which represents the change in temperature difference (delta T) between flap and control sites over a specified time period, was calculated at each time point. Of 10,000 derivations, only once did C delta T greater than 1.8 degrees C fail to identify a microvascular thrombosis, and 17 times a false alarm was given. Therefore, when properly applied and interpreted, the sensitivity of surface-temperature recording is 98 percent, and its predictive value is 75 percent, making it a simple, inexpensive, and highly reliable technique of free-flap monitoring. The thermodynamics behind surface temperature recording is reviewed, pointing out the pitfalls that have to be avoided in order to improve the reliability of this technique. PMID- 1741474 TI - Simultaneous rupture of the ligamentum patellae, medial collateral, and anterior cruciate ligaments. A case report. AB - We report a case of simultaneous rupture of the ligamentum patellae, medial collateral, and anterior cruciate ligaments. The full extent of the injury was not recognized on clinical examination. Although this is a rare combination of injuries, the integrity of the extensor mechanism should always be confirmed in knee injuries. PMID- 1741475 TI - Stress fractures of the sacrum in runners. Two case reports. PMID- 1741476 TI - Morphological patterns in the developing vertebrate retina. AB - Changes in the morphology of the early optic cup were observed in embryos of two distantly-related vertebrate species, a teleost fish, northern pike (Esox lucius), and chicken (Gallus gallus). A similar morphological pattern was noted to appear in both species shortly after the involution of the optic vesicle and the formation of the inner retinal layer. At a gross level, three notches were observed in the retinal margin at approximately nasal, dorsal, and temporal positions, while in histological sections a sharp constriction was found in the thickness of the dorsal retinal layer. In both species, this dorsal constriction appeared to be continuous with the central or dorsal notch. The time of appearance and configuration of this morphological pattern is intriguingly similar to the specification and polarity of retinal positional markers, and suggest a segmentation hypothesis for the origin of retinal polarity. PMID- 1741477 TI - Structural arrangement of the extracellular matrix network during myocardial development in the chick embryo heart. AB - We analyzed the extracellular matrix and the connective tissue of the developing chick myocardium ("myocardial interstitium"). The importance of this myocardial element for heart function has been well documented both for the normal and pathologic adult hearts. However, little information is available on the organization of the embryonic myocardial interstitium and its modifications during development and increasing intracardiac pressure. In the present study we used light and scanning electron microscopic techniques, and lectin probes to study the interstitium of the ventricular myocardium of chick embryos from stage 29 (day 6 of development) until hatching. Our observations trace the progressive appearance and organization of the elements of the extracellular matrix, comprising the epimysium, perimysium and endomysium, which form a well-defined architectural network. Finally, we discuss the role of these elements of the extracellular matrix and their possible relation with the biomechanical properties of developing heart. PMID- 1741478 TI - Distribution of acetylcholinesterase and zinc in the visual cortex of the mouse. AB - The distributions of acetylcholinesterase (AChE) and zinc-containing boutons and their cells of origin in the visual cortex of the house mouse (Mus musculus domesticus) are described. The primary visual area is defined by both acetylcholinesterase and zinc staining. The AChE staining pattern is dark in upper layer I and layers IV and VI. It is light in layers II/III and V. The lack of a densely stained layer IV in the secondary visual cortices defines the borders between primary and secondary areas. Large, multipolar AChE-positive neurons are located throughout the cortical layers, but preferentially in layer VI. Dense zinc-positive neuropil in the primary visual cortex is apparent in layer Ib, upper layer II/III, and layers V and VI. Neurons that give rise to zinc containing boutons are situated in layers II/III and VI. The medial and lateral borders can be distinguished by a bold contrast of staining in lower layer II/III; the secondary areas have more zinc-positive neurons, and the neuropil stains darker. A surprising observation of this study is the disparity between the mouse and rat visual cortex of the AChE staining pattern. Layer V is very light in the mouse, whereas a dark stain has been described in layer V of the rat. Layer VI stains heavily in the mouse while less AChE activity has been observed in layer VI of the rat. PMID- 1741479 TI - Lectin binding sites in developing mouse limb buds. AB - The binding sites of the following biotinylated lectins were demonstrated in serial paraffin sections of fore- and hindlimb buds from day-9 to day-16 mouse embryos with the Avidin-Biotin-Peroxidase Complex (ABC) procedure: Concanavalin A (Con A), Soybean Agglutinin (SBA), Wheat Germ Agglutinin (WGA), Peanut Agglutinin (PNA), Ricinus Communis Agglutinin I (RCA), Ulex Europaeus I Agglutinin (UEA), and Dolichos Biflorus Agglutinin (DBA). Alternating neighbouring sections were used to compare the distribution of PNA staining, PNA staining after neuraminidase treatment (N-PNA) and the autoradiographic sites of [35S]-sulphate uptake. Unspecific binding sites common to all lectins tested were observed in periderm and chondrocytes. Several lectin affinities were seen in the undifferentiated mesoderm (Con A, WGA, RCA), blood vessels (WGA, PNA, N-PNA, RCA, UEA, DBA) and macrophages (Con A, WGA, N-PNA, RCA). A very selective and mainly extracellular affinity to N-PNA was demonstrated in the condensed preskeletal mesoderm, where it characterizes indistinct prospective chondrogenic, perichondral and pre-articular areas. Comparison with the distribution pattern of [35S]-sulphate uptake and other previously published histochemical data suggests that N-PNA staining occurs at the late blastema stage, i.e. after the stage of cell condensation and before the earliest deposit of stainable matrix in chondrogenic areas. This property later disappears from the chondrifying rudiments, and is maintained in perichondral and pre-articular tissues. Surprisingly, only the pre-articular areas bind PNA without pretreatment with neuraminidase. A transient RCA binding probably related to terminal morphogenesis was detected in the undifferentiated distal part of the predigital columns of day 12 and day-13 limb buds. From the day-13 stage onwards, diverse new lectin affinities appeared in differentiating tissues, such as pretendinous rudiments, perichondrium and prospective periosteum, muscular connective tissue, myotubes, superficial fasciae and prospective dermis. A strong SBA and PNA staining was also detected in the extracellular matrix associated with the epithelial septa separating the roots of the digits in day-15 and day-16 limb buds. PMID- 1741480 TI - Axon contacts and acetylcholinesterase activity on chicken intrafusal muscle fiber types identified by their myosin heavy chain composition. AB - Muscle spindles of 8-week old chicken tibialis anterior muscles were examined to determine if specific intrafusal fiber types were also characterized by differences in motor innervation. Incubation with a monoclonal antibody against myosin heavy chains permitted the identification of strongly reactive, moderately reactive and unreactive intrafusal fibers. The innervation of each fiber type was evaluated in silver-impregnated sections, and in sections incubated with a monoclonal antibody against acetylcholinesterase. There was no acetylcholinesterase activity at the midequator of any fiber. At the juxtaequator and at the pole strongly reactive fibers typically exhibited fewer axon contacts and less acetylcholinesterase activity than unreactive and moderately reactive fibers. Differences were also recognized at neuromuscular junctions in the size and shape of acetylcholinesterase-positive sites. At the juxtaequator and at the pole strongly reactive fibers and moderately reactive fibers displayed significantly more small, dot-like acetylcholinesterase sites than unreactive fibers. On the contrary, the greatest number of larger, stout sites was found on unreactive fibers and the least number on strongly reactive fibers. Moderately reactive fibers took an intermediate position. The results indicate that myosin heavy chain-based chicken intrafusal fiber types are also set apart by differences in innervation. PMID- 1741481 TI - Vascular anatomy of a dicephalic cat. AB - The arterial and venous systems of the neck and heads of a dicephalic iniodymic monosomic cat are described. In the arterial system, an anomalous lingual branch of the right external carotid formed a large subhyoid arch, extending to the midline between both heads, giving off branches supplying the medial aspect of both heads and terminating in two medial internal carotid arteries each for the right or left head. This vessel was considered as an anomalous supernumerary common carotid artery. In the venous system, each lingual branch of linguofacial veins united and formed an anomalous venous arch. It received rostrally a long midline vein running between both heads and connecting with the medial internal jugular system. This vein received tributaries from the left and right heads and was considered as a supernumerary jugular vein. From these observations, and those of others in the literature, it can tentatively be suggested that, in congenital cephalic duplications in domestic mammals, the arterial blood supply for the medial aspect of both heads tends to come from the lingual branch of the external carotid artery, with an unexplained prevailing contribution of the right external carotid system. Two different venous patterns have been observed. In animal especies exhibiting a hyoid venous arch, such as carnivores, a midline supernumerary external jugular vein draining at the anomalous junction between lingual veins of both heads is formed, whilst in animals lacking a constant hyoid venous arch, such as ruminants, an asymmetrical supernumerary external jugular vein draining into the right "normal" external jugular vein has been repeatedly described. PMID- 1741482 TI - Unlayered polymicrogyria: structural and developmental aspects. AB - Unlayered polymicrogyria was analyzed in four patients with established lesions and in one 19- to 20-week-old fetus with lesions in a formative stage whose mother had suffered a serious accident two weeks before. Polymicrogyria occurred at the banks of porencephalic, sylvian clefts in three cases, and bilaterally in the watershed areas of the parieto-occipital lobes in a fourth case. Periventricular neuronal heteropias were found in these cases. Cortical lesions in the fetus were distributed along the watershed zones of the middle cerebral artery. Serial sections revealed that the appearance of microgyria was the result of radial tissue cleavage of the cerebral cortex, as shown by the increased numbers of blood vessels and astrocytes forming a tissue scar. Golgi studies disclosed that the different neuronal types were positioned at the apropriate cortical depths in the microgyric cortex. On the other hand, heterotopic nodules were composed of pyramidal and non-pyramidal neurons usually found in the upper cortical layers in the normal cortex. These features indicate that unlayered polymicrogyria is produced by circulatory failure occurring before the end of the period of neuroblast migration to the cortical plate. Circulatory failure in the radial and unbranched arteries that penetrate from the meningeal surface and vascularize the cerebral cortex at midgestation may result in radial tissue necrosis of the cortical mantle, whereas failure in the distal, terminal territories of these blood vessels may damage radial glial fibres and impair the last migration of neuroblasts. The particular morphology of this cortical abnormality finally depends on the imbalance in the tangential growth of adjoining cortical areas variably destroyed by tissue necrosis. PMID- 1741483 TI - Electron microscopic evidence on the acrosomal status of bound sperm and their penetration into human hemizonae pellucida after storage in a buffered salt solution. AB - The hemizona assay (HZA) was developed to evaluate sperm binding potential using microbisected human zona pellucida. In this study, eight human oocytes stored in a buffered salt solution for 60 days were bisected into two identical hemispheres (hemizonae) and coincubated with the spermatozoa from a fertile man. All evaluated spermatozoa were tightly bound to the outer surface or had begun penetration into the zona pellucida. The hemizonae with bound spermatozoa were prepared and fixed for transmission electron microscopy (TEM) using standard techniques. Among the 108 sperm bound to the zone we were able to evaluate 25 by TEM. Twenty (80%) of the zona bound spermatozoa were partially or completely acrosome reacted, while six (20%) of the zona bound sperm had intact acrosomes. Acrosome intact, partially acrosome reacted and completely reacted spermatozoa were observed within the zona. Penetration pathways or tunnels were seen within the zona matrix. The results illustrate, that typically spermatozoa tightly bound the human zona pellucida show induction of the acrosome reaction. Importantly, following storage of human eggs in salt solution (buffered to 7.4), the zona pellucida retain their biological and functional characteristics for at least 90 days. PMID- 1741484 TI - The hemizona assay (HZA) as an experimental model to evaluate the inhibition of sperm binding to the murine zona pellucida by isolated zona pellucida protein. AB - Compelling evidence has demonstrated that zona binding represents gamete recognition by sperm binding with high affinity and specificity to complex glycoproteins of the zona pellucida. In the present study we evaluated the hemizona assay (HZA) in the investigation of the interaction of mouse spermatozoa with unfertilized murine oocytes and hemizonae after exposure to solubilized murine zonae pellucidae proteins. The zonae pellucidae were isolated from ovarian tissue following described mincing techniques. The sperm binding characteristics of murine spermatozoa were studied by using SDS-PAGE isolated ZP2 (+/- 120 Kd) and ZP3 (+/- 83 Kd) components of the zona pellucida. Sperm receptor activity was examined in a competitive gamete binding fashion using the HZA as an indicator of sperm/zona interaction. The results illustrated that isolated, solubilized ZP2 and ZP3 glycoprotein moieties of the zona pellucida inhibited sperm binding to hemizonae and oocytes when compared to controls, and that the HZA can be utilized as an internally controlled homologous bioassay to evaluate the effects of zona pellucida proteins on tight binding of spermatozoa to the zona pellucida. PMID- 1741485 TI - Male alcohol consumption and fecundity in couples attending an infertility clinic. AB - The relationship between male alcohol intake and fertility was studied for 258 couples attending an infertility clinic. 21% consumed less than 1 unit per week on average, 10% consumed between 1 and 5 units per week, 23% consumed between 6 and 10 units per week, 27% consumed 11 to 20 units per week and 19% consumed more than 20 units per week. There was no significant association between alcohol consumption and any semen parameter. 110 men had a female partner who was apparently normal. There was no significant difference in the alcohol intake between the 'normal' and 'abnormal' female groups. Couples were followed-up for up to 32 months. Sixteen women had a treatment independent conception within the 'normal' female group. There was no significant association between the amount of alcohol consumed per week and the fertility outcome. PMID- 1741486 TI - Male cigarette smoking and fecundity in couples attending an infertility clinic. AB - The relationship between male cigarette smoking and fertility was studied for 330 couples attending an infertility clinic. 59% did not smoke, 10% smoked between 1 and 5 per day, 8% smoked between 6 and 10 per day, 16% smoked 11-20 per day and 7% smoked more than 20 per day. There was no significant association between smoking and any semen parameter. 138 men had a female partner who was apparently normal. There was no significant difference in smoking habits between the 'normal' and 'abnormal' female groups. Couples were followed-up for up to 32 months. Nineteen women had a treatment independent conception within the 'normal' female group. There was no significant association between the number of cigarettes smoked and the fertility outcome. PMID- 1741487 TI - Melatonin and aromatase stimulating activity of human seminal plasma. AB - Melatonin concentrations and aromatase stimulating activity were determined in human seminal plasma and correlated with sperm density and motility. Aromatase stimulating activity was determined with an in vitro rat granulosa cell system and melatonin by radioimmunoassay. Compared to normal semen, aromatase stimulating activity was lower in azoospermic individuals, while melatonin was higher in oligospermic and azoospermic samples. Aromatase stimulating activity correlated positively with sperm concentrations and a negative correlation was found between melatonin and sperm progression. These findings suggest that low sperm production is associated with low aromatase stimulating bioactivity in seminal plasma; and melatonin may have an effect upon both sperm production and motility. PMID- 1741488 TI - Antisperm antibodies in young boys. AB - The authors report the results of antisperm antibody tests carried out on a group of 159 pre-pubertal boys suffering from various testicular pathologies. The data show that 21% of the patients' sera showed antibody activity against antigens on the sperm of healthy fertile donors. None of the control sera was ASA positive. Some differences were observed in pathology and age distribution of positivity. PMID- 1741489 TI - DNA hybridization study using Y-specific probes in an XX-male. AB - A 30-year-old male attended the Toyama Medical and Pharmaceutical University Hospital with the chief complaint of infertility. Physical examination showed bilateral small testes and the semen contained no sperm. Hormonal studies revealed hypergonadotropic hypogonadism and cytogenetic studies showed a 46,XX karyotype. High-resolution banding showed no abnormalities in both of the X chromosomes. Histological examination of both testes showed germinal aplasia and the proliferation of Leydig cells. The diagnosis of XX-male was made from the above findings. A DNA hybridization study using 17 Y-specific probes revealed the presence of a major part of the short arm of the Y chromosome, which had presumably been translocated to the X chromosome. The translocated Y short arm had a small deletion within it. PMID- 1741490 TI - Epidermal growth factor (EGF) is not an index of seminiferous tubular function. AB - Epidermal growth factor concentrations and amounts per ejaculate were determined in 162 infertile men and in a control group of 50 pregnancy-proven fertile men. No differences were found between those groups. The group of infertile patients was divided into sub-groups according to their sperm density. EGF values in those sub-groups were not significantly different. There was no correlation between EGF concentrations and the variables of the sperm analysis that were measured. All these data suggest that EGF is not an index of gonadal function. This may be due to the fact that probably most EGF in seminal plasma is of prostatic origin. PMID- 1741491 TI - How frequent is unintentional childlessness in Germany? AB - A representative sample of 1,019 married men and 1,133 women of reproductive age was interviewed and revealed that 21.5% had no children. Of these, 20% stated that their childlessness was deliberate. Of those who had not conceived about two thirds (men: 31%, women: 60%) had already sought medical advice. The men surveyed tended to delay seeking medical advice for longer than the women do, who do so within one or two years. This indicates that there is a deficit in the data on men which results in a lack of knowledge concerning the possible reasons for infertility. PMID- 1741492 TI - Intrauterine insemination with semen of oligozoospermic men: effectiveness of the continuous-step density gradient centrifugation technique. AB - There has been an argument as to whether the intrauterine insemination (IUI) substantially improves pregnancy rate in cases of oligoasthenozoospermia. The present study evaluates the efficiency of the IUI with the use of the life table analysis. The insemination was performed after washing and concentrating sperm using the continuous-step density gradient centrifugation reported in our previous papers. The number of IUI cycles studied was 222 (46 couples), in 13 cases of which pregnancy was established with a pregnancy rate of 28.3%. The cumulative probability of conception reached to 57% at the eleventh cycles of the IUI treatment. These results suggest that the potential efficiency of the IUI for the oligo-asthenozoospermic cases is high if the sperm is processed in a proper method. PMID- 1741493 TI - Does magnesium sulfate alter the maternal cardiovascular response to vasopressor agents in gravid ewes? AB - Magnesium sulfate (MgSO4) attenuates the maternal compensatory response to hemorrhage in gravid ewes, perhaps by decreasing the response to endogenous vasopressors. The purpose of this study was to determine whether MgSO4 alters the cardiovascular response of gravid ewes to vasopressor agents. Sixteen gravid ewes underwent a series of experiments consisting of administration of two exogenous and two endogenous vasopressors, each with and without a concurrent MgSO4 infusion. Dose-response curves were constructed for phenylephrine (an alpha 1 adrenergic agonist), ST-91 (an alpha 2-adrenergic agonist), angiotensin II, and arginine vasopressin (AVP). MgSO4 significantly attenuated the increase in maternal mean arterial pressure and systemic vascular resistance and the decrease in cardiac output during ST-91 infusion but not during phenylephrine, angiotensin II, or AVP infusions. MgSO4 significantly attenuated the increase in uterine vascular resistance during phenylephrine, ST-91, and angiotensin II infusions and the decrease in uterine blood flow during phenylephrine and angiotensin II infusions. MgSO4 also appeared to attenuate the decrease in uterine blood flow during ST-91 infusion (P = 0.067). The present study suggests that MgSO4 antagonizes the effects of alpha 1-adrenergic agonists, alpha 2-adrenergic agonists, and angiotensin II on the uterine vasculature, thus providing a level of protection for the fetus in situations of maternal stress. PMID- 1741494 TI - Halothane depresses D600 binding to bovine heart sarcolemma. AB - Volatile anesthetics exert their negative inotropic effects by interfering with Ca2+ homeostasis in the myocardial cell. The mechanism of this dose-dependent action is uncertain. 3H-D600 (3H-Gallopamil), a Ca(2+)-channel antagonist, binds to the voltage-dependent Ca2+ channels (VDCC) in a specific, saturable, and reversible manner. We used this ligand to study the effect of halothane on the binding characteristics of the VDCC in purified bovine heart sarcolemma. Cardiac sarcolemmal vesicles were isolated from fresh bovine heart by differential centrifugation and filtration. 3H-D600 equilibrium binding assays were performed in the presence or absence of 1.0 mM unlabeled D600 to determine total and nonspecific binding in room air and at 0.7, 1.3, and 2.5% (vol/vol) halothane. Halothane produced a significant dose-dependent and reversible depression of 3H D600 specific binding in bovine heart sarcolemma. Depression was completely reversed when halothane had evaporated from the samples prior to filtration. Halothane 1.3% (vol/vol) produced a 40% reduction in the maximum binding capacity. The dissociation constant was not affected by any concentration of halothane. One mechanism by which the volatile anesthetics may induce negative inotropism is through the reduction of functional VDCCs in the heart, leading to reduction of Ca2+ entry. The results of this study support this hypothesis. PMID- 1741495 TI - Enhancement by propofol of epinephrine-induced arrhythmias in dogs. AB - Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine induced arrhythmias in a dose-dependent manner in dogs. PMID- 1741496 TI - Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. AB - Although epinephrine increases cerebral blood flow (CBF) and left ventricular blood flow (LVBF) during cardiopulmonary resuscitation (CPR), the effects of high dosages on LVBF and CBF and cerebral O2 uptake have not been examined during prolonged CPR. We determined whether log increment dosages of epinephrine would enhance LVBF and CBF and cerebral O2 uptake in an infant swine CPR model. We compared these responses with epinephrine to those with the alpha-adrenergic agonist, phenylephrine. CPR was performed in five groups (n = 6) of pentobarbital anesthetized piglets (3.5-5.6 kg) receiving a continuous epinephrine infusion (0, 1, 10, and 100 micrograms.kg-1.min-1) or phenylephrine infusion (40 micrograms.kg 1.min-1). Plasma epinephrine concentrations increased 10-100-fold in the control group during CPR and in a stepwise manner such that concentrations were increased by more than 10(4) in the 100 micrograms.kg-1.min-1 epinephrine group. In the control group with no epinephrine infusion, LVBF decreased to less than 10 ml.min 1.100 g-1 by 5 min of CPR. With epinephrine in dosages of 10 and 100 micrograms.kg-1.min-1, LVBF at 5 min was 75 +/- 19 and 44 +/- 15 ml.min-1.100 g 1, respectively, which was significantly greater than values in the control group. With more prolonged CPR, LVBF remained significantly greater than that in the control group but only at 10 micrograms.kg-1.min-1 of epinephrine. Phenylephrine also increased LVBF for 10 min of CPR when compared with the control group. All dosages of epinephrine and phenylephrine maintained CBF close to prearrest values for 20 min of CPR. With prolonged CPR, 10 and 100 micrograms.kg-1.min-1 epinephrine resulted in significantly greater CBF than that in the control group. Incremental dosages of epinephrine did not statistically increase cerebral O2 uptake or lower the cerebral fractional O2 extraction when compared with the control group, despite the higher CBF that was generated. In this immature animal CPR model, 10 micrograms.kg-1.min-1 epinephrine is an optimal dosage for maximizing both CBF and LVBF, a dosage that substantially exceeds the current recommended epinephrine dosage for human infant CPR. In addition, for short periods of CPR, 40 micrograms.kg-1.min-1 phenylephrine increases CBF and LVBF to levels similar to those generated by high dosages of epinephrine. PMID- 1741497 TI - Potassium channel blockers potentiate impulse inhibition by local anesthetics. AB - The ability of local anesthetics to reduce the amplitude of compound action potentials (CAP) of frog sciatic nerve was examined in the absence and presence of agents that selectively block K+ channels. In the presence of lidocaine concentrations that inhibit the CAP by about 20% at low frequencies of stimulation (1 per min, "tonic inhibition"), the addition of the K(+)-channel blocker tetraethylammonium ion (TEA, 12 mM) increased this inhibition by another 15%. Furthermore, the use-dependent inhibition induced by lidocaine at higher stimulation frequencies (5-20 Hz, "phasic inhibition") was markedly enhanced by TEA: at 20 Hz it increased from 35% with lidocaine alone to 63% with lidocaine plus TEA. A comparable potentiation was rendered by 3,4-diaminopyridine (1 mM), a different K(+)-channel blocker. Similarly, phasic inhibition by bupivacaine also was enhanced by TEA. The K(+)-channel blockers alone slightly depolarized the resting membrane, broadened and elevated the CAP, produced no phasic inhibition, and, during repetitive stimulation, resulted in a less negative steady-state repolarization potential than at rest. Both the broadening of CAP and the depolarizing actions of K(+)-channel blockers increased the presence of open and inactivated states of the neuronal Na+ channels, and thereby enhanced the binding of local anesthetic. The inhibitory actions of saxitoxin, a Na(+)-channel blocker that binds equally well to all channel states, were not potentiated by TEA. PMID- 1741498 TI - Comparison of halothane, enflurane, and isoflurane with nitrous oxide on contractility and oxygen supply and demand in isolated hearts. AB - The authors' aim was to examine direct cardiac responses to isoflurane, enflurane and halothane, as altered during mild hypoxia by the substitution of nitrogen (N2) for oxygen (O2), and additionally by the substitution of nitrous oxide (N2O) for N2. Heart rate, atrioventricular conduction time, left ventricular pressure (LVP), peak positive and negative derivatives of LVP (dLVP/dtmax), coronary flow, O2 delivery (DO2), percent O2 extraction, and myocardial O2 consumption (MVo2) were examined in 47 isolated guinea pig hearts. Changes in the ratio of DO2 to MVO2 indicated the relationship of autoregulation of coronary flow to myocardial O2 utilization. Each heart was first exposed to 96% O2 and then randomly exposed to 48% N2 and 48% N2O alone and with three equivalent concentrations of one of three volatile anesthetics: isoflurane (n = 15), halothane (n = 16), or enflurane (n = 16). Results were as follows: 1) N2 alone significantly decreased LVP, +dLVP/dtmax and -dLVP/dtmax, DO2 and MVO2; increased coronary flow; and produced no change in heart rate, atrioventricular conduction time, percent O2 extraction, or the DO2/MVO2 ratio. 2) Compared to N2, N2O alone only produced additional significant decreases in LVP and +dLVP/dtmax. 3) In the presence of N2 or N2O, each volatile anesthetic caused significant stepwise decreases in heart rate, LVP, +dLVP/dtmax and -dLVP/dtmax, MVO2, and percent O2 extraction; no additional change in coronary flow or DO2; and a stepwise increase in the DO2/MVO2 ratio. The effects of halothane and enflurane were generally greater than those of isoflurane. 4) Each volatile anesthetic caused an additive, parallel depression of LVP and percent O2 extraction as a function of MAC with N2O compared to N2. This study demonstrates that the direct negative inotropic effects of halothane and enflurane are more pronounced than those of isoflurane and are accompanied by a greater reduction in O2 utilization by halothane and enflurane than by isoflurane in the presence of mild hypoxia alone or with the addition of N2O. The study also demonstrates that N2O accentuates the negative inotropic effects of volatile anesthetics during reduced O2. PMID- 1741499 TI - Halothane alters control of intracellular Ca2+ mobilization in single rat ventricular myocytes. AB - In an attempt to understand the cellular mechanisms underlying volatile anesthetic-induced myocardial depression, halothane-induced negative inotropy was investigated in an animal model through continuous monitoring of intracellular Ca2+ concentration [( Ca2+]i) in rat ventricular myocytes loaded with fura-2. Single cells were stimulated with 15 mM caffeine or 15 mM extracellular K+ (K+O) or were paced by extracellular glass suction pipette electrode. With each stimulus modality, halothane (0.6-1.5%) caused a significant (P less than 0.05) and dose-dependent depression of the Ca2+ transient. Caffeine and electrically stimulated Ca2+ transients were reduced, in 1.5% halothane, to 35 +/- 14 and 42 +/- 8% of control, respectively. Resting or basal [Ca2+]i was unaffected by halothane. Halothane did not elicit spontaneous Ca2+ transients in these cells. Single cells stimulated by trains of electrical stimuli at 1.0, 1.5, and 2.0 Hz showed a change in [Ca2+]i from prestimulus levels to a stimulated baseline steady state that appeared to increase with stimulus frequency. Halothane at 0.7% increased the change in resting to stimulated baseline [Ca2+]i and depressed net transients (P less than 0.05) at 1.0 and 1.5 Hz. In contrast, 0.1 microM ryanodine depressed the Ca2+ transients in myocytes stimulated by trains of stimuli, but did not potentiate the change in stimulated baseline [Ca2+]i at any pacing rate. The results are consistent with the hypothesis that halothane reduces Ca2+i availability by causing a net loss of Ca2+ from the sarcoplasmic reticulum. The results from experiments using onset of pacing to induce a sudden increase in Ca2+i load in previously quiescent myocytes suggest that halothane may act to limit sarcoplasmic reticulum and/or sarcolemmal uptake/extrusion mechanisms, as compared to ryanodine, which depletes sarcoplasmic reticulum Ca2+ stores without affecting reuptake and extrusion. PMID- 1741500 TI - Intractable pharyngeal spasm following tracheal extubation in a patient with undiagnosed tetanus. PMID- 1741501 TI - Anaphylaxis during anesthesia: use of radioimmunoassays to determine etiology and drugs responsible in fatal cases. PMID- 1741502 TI - Another cause of upper airway obstruction. PMID- 1741503 TI - The first anesthetic mixture. PMID- 1741504 TI - Air entrainment during cardiopulmonary bypass surgery. PMID- 1741505 TI - Should calcium be administered prior to separation from cardiopulmonary bypass? PMID- 1741506 TI - Postintubation croup in children. PMID- 1741507 TI - Transparent dressing is useful for the secure fixation of the endotracheal tube. PMID- 1741508 TI - Does systemic anticoagulation increase the risk of internal jugular vein cannulation? PMID- 1741509 TI - More on standardized alarms. PMID- 1741510 TI - Glycopyrrolate and the central anticholinergic syndrome. PMID- 1741511 TI - Applications of molecular genetics to anesthesiology. PMID- 1741512 TI - EDRF/nitric oxide. The endogenous nitrovasodilator and a new cellular messenger. PMID- 1741513 TI - Adverse respiratory events infrequently leading to malpractice suits. A closed claims analysis. AB - Adverse outcomes associated with respiratory events are the single largest class of injury in the American Society of Anesthesiologists Closed Claims Project (762 of the 2,046 cases, 37%). Inadequate ventilation, esophageal intubation, and difficult tracheal intubation are the most common mechanisms of respiratory related adverse outcomes. An analysis of closed claims data regarding these mechanisms has been reported previously. This report is concerned with 300 claims for five other less common but important categories of respiratory-related adverse outcomes in which recurrent themes of management error or patterns of injury could be identified: airway trauma, pneumothorax, airway obstruction, aspiration, and bronchospasm. Airway trauma (97 claims, 5% of the database) was associated with difficult intubation in 41 (42%) of the cases and the most frequent sites of injury were the larynx, pharynx, and esophagus. Pneumothorax (67 cases, 3% of the database) was usually either needle-related (block or central vascular catheter placement) or airway management-related (instrumentation or barotrauma). Airway obstruction (56 claims, 3% of the database) occurred in the upper airway in 39 (70%) of the cases. Aspiration (56 claims, 3% of the database) usually occurred during general anesthesia, either during induction prior to tracheal intubation or during maintenance of anesthesia delivered via mask. Bronchospasm (40 claims, 2% of the database) tended to occur during induction of general anesthesia in patients with a history of asthma or chronic obstructive pulmonary disease and/or smoking. The incidence of severe injury (brain damage and death) among these cases in the five categories was 47% overall, ranging from 12% in airway trauma claims to nearly 90% in claims for airway obstruction and bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741514 TI - Time course of ventilatory depression following induction doses of propofol and thiopental. AB - To improve our understanding of the respiratory pharmacology of intravenous induction agents, the authors compared the acute effects of intravenous (iv) propofol 2.5 mg.kg-1 and iv thiopental 4.0 mg.kg-1 on the ventilatory response to CO2 (VeRCO2) of eight healthy volunteers. The slope of VeRCO2 decreased from 1.75 +/- 0.23 to a minimum of 0.77 +/- 0.14 1.min-1.mmHg-1 (mean +/- standard error) 90 s after propofol; similarly, the slope of VeRCO2 decreased from 1.79 +/- 0.22 to a minimum of 0.78 +/- 0.23 l.min-1.mmHg-1 30 s after thiopental. For both drugs, the slope was less than control in the 0.5-5-min period after injection (P less than 0.05). The slope returned to baseline within 6 min after thiopental; in contrast, after propofol, the slope remained less than control for the entire 20 min follow-up period (P less than 0.05 at 6-10, 11-15, and 16-20 min after injection). Also, from 6-10, 11-15, and 16-20 min after injection, the slope was less after propofol than at corresponding times after thiopental (P less than 0.05). Recovery of consciousness was approximately 4 min slower after propofol than after thiopental; nonetheless, awareness scores returned to baseline within 14 min after both drugs. The authors conclude that propofol 2.5 mg.kg-1 iv produces longer-lasting depression of VeRCO2 than a 4.0 mg.kg-1 iv dose of thiopental; after propofol, ventilatory depression may persist despite apparently complete recovery of consciousness. PMID- 1741515 TI - Biochemical markers of anaphylactoid reactions to drugs. Comparison of plasma histamine and tryptase. AB - Adverse reactions to drugs require that their mechanisms be elucidated, particularly when anaphylaxis is suspected. Early diagnosis can be achieved by plasma histamine measurements. Unfortunately, the short plasma half-life of histamine and the difficulties in handling the sample usually preclude this measurement, although a sensitive radioimmunologic kit is routinely available. It has been recently suggested that mast cell tryptase, a component of the mast cell granules, could provide an alternative to histamine determination. We have measured plasma histamine and tryptase in 19 patients who developed possible anaphylactoid reactions to anesthetic or other drugs. Eight patients had increased values for both histamine and tryptase. In 4 a muscle relaxant drug was proved responsible for the reaction. Six patients had normal levels for both substances. In each case, the clinical signs of anaphylaxis were moderate. Two patients had normal histamine and high tryptase concentrations, due to late sampling (greater than 5 h). In 2 other patients, histamine was high, with normal tryptase: in 1, muscle relaxant allergy was further demonstrated. Tryptase half life was equal to 90 min in 3 patients. At least 15 min was necessary to reach the peak level when the responsible drug was administered intravenously. The best time for measuring tryptase was 1-2 h after the reaction (not greater than 6 h), whereas for histamine it was 10 min to 1 h. We conclude that measurement of plasma tryptase along with measurement of plasma histamine may aid in diagnosis of anaphylaxis. PMID- 1741516 TI - Long-lasting epidural sensory blockade by n-butyl-p-aminobenzoate in the terminally ill intractable cancer pain patient. AB - An aqueous suspension of n-butyl-p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally in terminally ill cancer patients with intractable pain. The suspension consisted of 10% BAB and 0.025% of the nonionic surfactant polysorbate 80 in 0.9% sodium chloride. Twelve consecutive patients received epidural BAB because pain was uncontrollable either by palliative radiotherapy or oral or epidural administrations of analgesics. The catheter or injecting needle was positioned at the segmental level of the pain. Repeated epidural injections were administered. In all patients, long-lasting sensory blockade (segmental analgesia) occurred, accompanied by a marked reduction or even absence of pain. In all patients, treatment with epidural opioids, alone or combined with local anesthetics, was no longer necessary. Five of the 12 patients did not require further administration of oral opioids. Motor, bowel, and bladder function were well preserved. In 6 patients, extensive necropsy of the spinal cord and spinal nerves did not reveal pathomorphologic changes. The outer aspect of the dura showed signs of focal necrosis on microscopy, yet its collagen structure and thickness were unchanged. Epidurally, focal infiltrative reactions were seen. The epidural use of an extremely lipid soluble--hence hydrophobic--local anesthetic, with an exceptionally low pKa (2.3), formulated in suspension of the base, is conceptually innovative and needs further investigation. The authors conclude that the epidural administration of a BAB suspension may be an effective alternative to the neurolytic agents alcohol and phenol and may replace procedures such as cordotomy. Further investigation to determine the safety of BAB in this patient group appears warranted. PMID- 1741517 TI - Pharmacokinetics of amrinone during cardiac surgery. AB - Amrinone is a nonglycosidic noncatecholamine with both vasodilator and positive inotropic effects that may be administered to patients undergoing cardiac surgery. As an initial step toward elucidating the optimal dosage of amrinone for cardiac surgical patients we studied the pharmacokinetics of amrinone during and after cardiac surgery requiring cardiopulmonary bypass. The study population comprised 35 adult patients, each receiving a single dose of amrinone (0.75, 1.5, 2.0, or 2.5 mg/kg) administered into the venous reservoir near the end of cardiopulmonary bypass. Additionally, 15 of the 35 patients also received intravenous infusions of either 5 or 10 micrograms.kg-1.min-1. Arterial blood was sampled over the next 22 h, and plasma concentrations of amrinone were determined by high-performance liquid chromatography. Protein binding of amrinone, assayed by equilibrium dialysis, was 21.6 +/- 2.5%. The decay of amrinone concentrations in plasma over time was fit to a biexponential equation by nonlinear least squares regression. The manufacturer's recommended dose of 0.75 mg/kg followed by an infusion of 10 micrograms.kg-1.min-1 was inadequate to maintain the plasma concentration within the therapeutic range based on the pharmacodynamics of amrinone in patients with chronic congestive heart failure. This was due to significant redistribution of amrinone in the body after the loading dose. To maintain a therapeutic plasma concentration of 1.5-2.0 micrograms/ml, a larger loading dose or a supplemental loading dose as well as a continuous infusion is required. PMID- 1741518 TI - Minimum alveolar concentration of desflurane and hemodynamic responses in neonates, infants, and children. AB - We sought to determine the minimum alveolar concentration (MAC) and hemodynamic responses to desflurane in 72 fasting and unpremedicated full-term neonates, infants, and children up to 12 yr of age. The patients were divided into six groups (n = 12) according to age. After awake tracheal intubation, neonates were anesthetized with desflurane in oxygen and air. Infants greater than 1 month of age and all older children were anesthetized with desflurane in 100% oxygen, and their tracheas were intubated without muscle relaxation. MAC was determined using the "up-and-down technique" and logistic regression. Heart rate and systolic arterial pressure were recorded awake, at approximately 1 MAC desflurane before skin incision and at approximately 1 MAC during the peak hemodynamic responses to skin incision. We found that the relationship between MAC (mean +/- standard deviation) as determined by the up-and-down technique and age was quadratic, reaching a maximum value in infants 6-12 months of age: in neonates 0-1 month MAC was 9.16 +/- 0.02%, in infants 1-6 months 9.42 +/- 0.06%, in infants 6-12 months 9.92 +/- 0.44%, in children 1-3 yr 8.72 +/- 0.59%, in children 3-5 yr 8.62 +/- 0.45%, and in children 5-12 yr 7.98 +/- 0.43%. MAC values obtained using logistic regression were similar. Heart rate decreased an average of 16% before skin incision in infants 6-12 months of age and children 1-3 and 3-5 yr of age when compared to awake values (P less than 0.025) but did not change significantly in the remaining three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741519 TI - Effects of partial paralysis on the swallowing reflex in conscious humans. AB - The ability to swallow may be affected by administration of a small dose of muscle relaxant. To test the hypothesis that a subparalyzing dose of a muscle relaxant can impair swallowing, effects of partial paralysis produced by pancuronium on the swallowing reflex were investigated in eight conscious subjects. The swallowing reflex was induced by a bolus injection or a continuous infusion of distilled water into the mesopharynx. The swallowing function was assessed by electromyogram of suprahyoid muscles (EMGSH), mesopharyngeal pressure (Pmeso), and hypopharyngeal pressure (Phypo). Peripheral muscle activity was simultaneously determined by train of four ratio (TOFR) of hypothenar muscles to electrical stimulation of ulnar nerve and by hand grip strength (HGS). Following control measurements, measurements during partial paralysis and after recovery from partial paralysis were performed after intravenous administration of pancuronium 0.02 mg/kg. Partial paralysis significantly depressed EMGSH (bolus injection 44.1 +/- 10.0%, continuous infusion 55.9 +/- 10.2% of control value, P less than 0.01). Pmeso also significantly decreased (bolus injection 64.9 +/- 6.7 to 47.8 +/- 5.8 mmHg, P less than 0.01; continuous infusion 63.4 +/- 7.7 to 52.5 +/- 5.8 mmHg, P less than 0.05). The TOFR of peripheral muscles decreased to 81.4 +/- 6.7% of control value (P less than 0.01), and HGS was reduced from 44.6 +/- 1.9 to 39.4 +/- 2.0 kg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741520 TI - Isoflurane anesthesia and circadian temperature cycles in humans. AB - Cognitive performance in postsurgical patients may be impaired by disturbances of normal circadian rhythm analogous to those produced by rapid transmeridian travel ("jet lag"). We therefore tested the hypothesis that isoflurane anesthesia alone produces a phase-delay in the human circadian temperature rhythm. We monitored central body temperature rhythms (using an ingested sensor) in five young, healthy, male volunteers at 3-min intervals for a total of 5 days. On the 3rd day, 3 h of 1.0% isoflurane anesthesia was administered beginning at approximately 10:00 AM. Thiopental, opioids, and other medications were not administered; volunteers were kept normothermic during anesthesia. Visual inspection of the data confirmed that periodicity of the temperature cycles remained near 24 h and that the curve was sinusoidal. Data were fit using a two step sine and cosine regression for each 24-h period. Before anesthesia, volunteers demonstrated a consistent 24-h cycle, with a mean temperature (mesor) of 36.8 +/- 0.2 degrees C, amplitude of 0.8 +/- 0.2 degrees C, and time of maximum temperature (acrophase) of 3:06 PM +/- 2.4 h. Isoflurane anesthesia did not produce significant changes in the central temperature mesor. Peak-to-trough range (amplitude) of the temperature cycle was significantly reduced on the day of anesthesia (0.5 +/- 0.2 degrees C) but returned to normal on the subsequent day. Compared with the 2 days preceding isoflurane administration, there was no statistically significant change in acrophase on the day following anesthesia. These data do not support our hypothesis and suggest that the internal timer controlling circadian temperature cycles is resistant to clinical concentrations of isoflurane. PMID- 1741521 TI - Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. AB - Nitric oxide (NO) has recently been discovered to be an important endothelium derived relaxing factor and produces profound relaxation of vascular smooth muscle. To learn if NO could be a potent and selective pulmonary vasodilator, NO was inhaled by 16 awake lambs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by either the infusion of an exogenous pulmonary vasoconstrictor (the thromboxane analog U46619) or the endogenous release of thromboxane that occurs during the neutralization of heparin anticoagulation by protamine sulfate. Inhaling greater than or equal to 40 ppm of NO during a continuous U46619 infusion returned the PAP to a normal value, without affecting systemic blood pressure or vascular resistance. Pretreatment with the cyclooxygenase inhibitor indomethacin before infusing U46619 did not reduce the pulmonary vasodilatory effect of inhaled NO, and we conclude that the dilatory effect of NO on the lung's circulation is independent of cyclooxygenase products such as prostacyclin. Continuously inhaling NO at 180 ppm did not significantly reduce the mean peak thromboxane B2 concentration at 1 min after protamine injection; however, the mean values of pulmonary hypertension and vasoconstriction at 1 min were markedly reduced below the levels in untreated heparin-protamine reactions. Breathing NO at lower concentrations (40-80 ppm) did not decrease the mean peak PAP and PVR at 1 min after protamine but decreased the PAP and PVR values at 2, 3, and 5 min below those of control heparin-protamine reactions. Intravenous infusion of nitroprusside completely prevented the transient increase of PAP and PVR during the heparin-protamine reaction; however, marked concomitant systemic vasodilation occurred. Inhaled NO is a selective pulmonary vasodilator that can prevent thromboxane-induced pulmonary hypertension during the heparin-protamine reaction in lambs and can do so without causing systemic vasodilation. PMID- 1741522 TI - Wiener analysis of nonlinear feedback in sensory systems. AB - Experimental studies of certain sensory systems (e.g., vertebrate retinal cells and auditory fibers) have yielded qualitative evidence of the presence of nonlinear feedback. However, no methods have been available to provide the tools for quantitative analysis of this nonlinear feedback mechanism and subsequent modeling of the overall dynamics of these sensory systems. Recent results offer the analytical means to relate Wiener kernel measurements with corresponding nonlinear feedback models and, thus, the ability to model the overall dynamics of such sensory systems. Furthermore, our analytical results offer an explanation for experimentally observed changes in the waveform of Wiener kernel estimates obtained for different white-noise input mean and/or power levels. PMID- 1741523 TI - Asymptotic approach of generalized orthogonal functional expansions to Wiener kernels. AB - Wiener-like orthogonal functional expansions may be constructed with respect to test ensembles that are non-Gaussian, nonwhite, or both. Although the original Wiener expansion has particularly advantageous analytical properties, orthogonal expansions constructed with respect to other ensembles have practical advantages for laboratory implementation. We show how functional expansions based on two classes of input ensembles--white but non-Gaussian discrete noises and the sum of sinusoids--converge to the standard Wiener kernels. For discrete noises, the disparity between the standard and nonstandard kernels of a linear-static nonlinear transducer is proportional to the kurtosis of the input signal and inversely proportional to the ratio of the integration time of the linear filter to the time discretization. For the sum of sinusoids, the disparity is inversely proportional to the effective number of sinusoids passed by the initial linear stage. PMID- 1741524 TI - Practical identification of functional expansions of nonlinear systems submitted to non-Gaussian inputs. AB - Time-domain identification of nonlinear systems represented by functional expansions is considered. A general framework is defined for the analysis of three identification methods: the widely used cross-correlation method, Korenberg's method, and a suboptimal least-squares method based on a stochastic approximation algorithm. First, the major characteristics of the underlying estimation problem are pointed out. Then, the identification methods are interpreted as approximations to an optimal estimator, which helps gain insight into their internal functioning and to the investigation of their connections and differences. Examination of results previously published and of the simulations reported in this article indicate that stochastic approximation is an interesting alternative to other existing methods. Identification of a biological system stimulated by a non-Gaussian input confirms the practicality of this approach. PMID- 1741525 TI - Parallel cascade identification and kernel estimation for nonlinear systems. AB - We consider the representation and identification of nonlinear systems through the use of parallel cascades of alternating dynamic linear and static nonlinear elements. Building on the work of Palm and others, we show that any discrete-time finite-memory nonlinear system having a finite-order Volterra series representation can be exactly represented by a finite number of parallel LN cascade paths. Each LN path consists of a dynamic linear system followed by a static nonlinearity (which can be a polynomial). In particular, we provide an upper bound for the number of parallel LN paths required to represent exactly a discrete-time finite-memory Volterra functional of a given order. Next, we show how to obtain a parallel cascade representation of a nonlinear system from a single input-output record. The input is not required to be Gaussian or white, nor to have special autocorrelation properties. Next, our parallel cascade identification is applied to measure accurately the kernels of nonlinear systems (even those with lengthy memory), and to discover the significant terms to include in a nonlinear difference equation model for a system. In addition, the kernel estimation is used as a means of studying individual signals to distinguish deterministic from random behaviour, in an alternative to the use of chaotic dynamics. Finally, an alternate kernel estimation scheme is presented. PMID- 1741526 TI - Decomposition of nonlinear non-Gaussian process and its application to nonlinear filter and predictor design. AB - An approach for decomposing of a Nonlinear Non-Gaussian Process (NNGP) is presented. A set of adjoin processes alpha's are first constructed based on the orthogonal principle so that the linear and nonlinear part of the process can be completely separated by a correlation operation without the statistical assumption on the process (i.e., it is not necessarily a Gaussian Process). The linear and nonlinear filters or predictors can then be designed and implemented independently and the consistency of parameters is guaranteed. An algorithm is given for a second order nonlinear process, and it can easily be extended to higher order cases if necessary. The method is first demonstrated by applying it to a nonlinear filter design problem, i.e., system identification. Finally, the necessity of a proposed decomposition procedure is proven by applying it to an example in which the parameters of a signal model are extracted from a version which is distorted due to the nonlinearity of the channel. PMID- 1741527 TI - Dissection of a nonlinear cascade model for sensory encoding. AB - Action potential encoding in the cockroach tactile spine neuron may be treated as a single-input, single-output dynamic nonlinear process, where the input is the electric current flowing across the neuronal membrane and the output is the resultant train of action potentials. The nonlinear behavior of the system may be characterized by a functional expansion method which efficiently and accurately yields similar kernels to the Wiener method. A simple nonlinear cascade consisting of sequential dynamic linear, static nonlinear, and dynamic linear components was identified and gives a good approximation to the response of the neuron to random stimulation. Next, we attempted to study the components of the cascade by the use of a drug, phentolamine, which selectively modifies the dynamic behavior of the encoder. Application of phentolamine to the neuron caused a significant change in the first dynamic linear component of the cascade without affecting the other components. The change was much larger than the variability between results obtained from individual animals. This finding has implications for the biophysical processes which are involved in the components of the cascade. PMID- 1741528 TI - Interpretation of functional series expansions. AB - While much research has been devoted to the implementation and application of Volterra and Wiener functional series expansions in the identification and characterization of biological systems, little effort has been focused on the fundamental problem of interpreting the resulting kernels. This paper describes the application of the series to the components of a known model of the human pupil control system. As more complicated elements are put together, insight into kernel interpretation is built up incrementally until the total system is identified. Practical limitations and methods are also discussed. PMID- 1741529 TI - The interpretation of kernels--an overview. AB - The kernel identification method is a powerful technique for mathematically representing the dynamic behavior of a nonlinear system. This technique has been applied to a number of physical and physiological systems. An important development which has enhanced the usefulness of the kernel method has been the interpretation of the internal structure of a system by examining the shapes of the higher-degree kernels. Examples of various nonlinear models with known structure are illustrated to show a repertoire of kernel shapes. Variations in parameters of these models result in well-defined changes in the shapes of the kernels. Also, examples are shown of kernels obtained from physiological systems to demonstrate how examination of kernel shapes can lead to accurate predictions of the dynamic behavior of the physiological system. Finally, limitations of the applicable range of the kernel identification method are discussed. PMID- 1741530 TI - Cellular engineering. AB - Cellular engineering applies the principles and methods of engineering to the problems of cell and molecular biology of both a basic and applied nature. As biomedical engineering has shifted from the organ and tissue level to the cellular and sub-cellular level, cellular engineering has emerged as a new area. A cornerstone of much of this activity is cell culture technology, i.e., the ability to grow living cells in the artificial environment of a laboratory. Cellular engineering includes the role of engineering in both basic cell biology research and in the making of products which use living cells, e.g., tissue engineering and bioprocess engineering. The former involves the use of living cells in the development of biological substitutes for the restoration or replacement of function, and the latter the use of living cells to manufacture a biochemical product, e.g., through the use of recombinant DNA technology. In fact, as biomedical engineering has expanded to include the cellular level, and bioprocess engineering has shifted in interest from microbial organisms to include mammalian cells, there are intellectual issues in which an interest is shared by these two formerly separate areas of engineering activity. Cellular engineering thus transcends the field of biomedical engineering. PMID- 1741531 TI - Airway insufflation. Increasing flow rates progressively reduce dead space in respiratory failure. AB - We have previously shown that airway insufflation (AI) reduces dead space (VD) and minute ventilation (VL) in patients with respiratory failure, and when used chronically leads to lowered and more stable arterial PCO2. The present study was designed to measure the effect of increasing AI flow rate on VD and other aspects of gas exchange in respiratory failure in order to examine the hypothesis that AI exerts its main physiologic effect by progressive reductions of VD. Five patients with varying degrees of respiratory failure caused by either restrictive or obstructive lung disease were studied by means of the specialized techniques we developed to analyze gas exchange during AI. At 1 L/min (as in transtracheal oxygenation), at 5 L/min, and 8 L/min, AI produced progressive reductions in VD, tidal volume, and VL. Contrary to our previous study, some of these patients accompanied the decrease in VD with not only decreases in VL but with slight rises in alveolar ventilation (VA) and decrements in arterial PCO2. The greatest percentile decreases in VD and VL occurred in those with the smallest initial control values for each of these parameters. In summary, AI exerts its main effects on gas exchange through the reductions in VD that it produces, and the accompanying decreases in VL and/or slight increases in VA seem to stem from the latter. PMID- 1741532 TI - Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease. AB - Intermittent positive pressure ventilation administered nocturnally via a nasal mask has been associated with improvements in pulmonary function and symptoms in patients with restrictive ventilatory disorders. We hypothesized that nocturnal nasal ventilation (NNV) would bring about similar improvements in patients with severe chronic obstructive pulmonary disease (COPD). The study used a randomized, crossover design, with subjects undergoing NNV or "standard care" for sequential 3-month periods. Of 23 patients with obstructive lung disease and a FEV1 less than 1 L who were initially enrolled, 4 were excluded because of obstructive sleep apnea prior to randomization. Among the remaining 19 patients, 7 withdrew because of intolerance of the nose mask, 5 were withdrawn because of intercurrent illnesses, and 7 completed both arms of the protocol. These latter 7 patients used the ventilator for an average of 6.7 h/night, and 3 of the 7 had partial relief of dyspnea during ventilator use. However, in comparison with studies performed upon initiation or after the standard care arm of the study, studies performed after 3 months of NNV revealed no improvements in pulmonary function, respiratory muscle strength, gas exchange, exercise endurance, sleep efficiency, quality or oxygenation, or dyspnea ratings. The only improvements observed were in neuropsychological function, possibly related to a placebo effect or another unknown mechanism. Despite the small sample size, our study indicates that NNV is not well tolerated by and brings about minimal improvements in stable outpatients with severe COPD. PMID- 1741533 TI - Reliability of noninvasive oximetry in black subjects during exercise and hypoxia. AB - The effect of skin pigmentation on the reliability of noninvasive oximetry, especially during exercise and hypoxia, has not been thoroughly investigated. This is the first study, to our knowledge, that specifically addresses this question. Thirty-three young black men performed multistage, steady-state cycle ergometry, breathing gas mixtures simulating different altitudes: 33 breathed gas simulating sea level (PIO2 = 146 mm Hg), 11 breathed gas simulating 2,300 m (PIO2 = 110 mm Hg), and 22 breathed gas simulating 4,000 m (PIO2 = 85 mm Hg). Co oximeter SaO2 determinations were performed in arterial blood samples obtained concurrently with ear oximetry that was measured using Hewlett-Packard 47201A (HP) and Blox IIA oximeters. The mean error or bias for the [HP - SaO2] and for [Biox IIA - SaO2] +/- 95% CI were: at simulated sea level (SaO2 greater than 96%): -0.4 +/- 0.3% and 2.1 +/- 0.3%; at simulated 2,300 m (range of SaO2 means, 89 to 94%): -0.8 +/- 0.5% and 3.5 +/- 0.9%; for simulated 4,000 m (range of SaO2 means, 75 to 84%): -4.8 +/- 1.6% and 9.8 +/- 1.8%, respectively. A better coefficient correlation was observed for all the pairs between SaO2 versus HP (r = 0.94, p less than 0.001, n = 279) than for the SaO2 versus Biox IIA (r = 0.80, p less than 0.001, n = 242). In conclusion, the HP oximeter appears to estimate SaO2 more accurately than the Biox IIA oximeter. The previously described overestimation for the Biox IIA ear oximeter and the underestimation for the HP ear oximeter at low SaO2 values in whites is exaggerated in blacks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741534 TI - Effect of theophylline on lung function tests, sleep quality, and nighttime SaO2 in children with cystic fibrosis. AB - The effect of theophylline (T) was studied in 12 children with cystic fibrosis (CF) (seven males and five females) aged 7 to 17 yr (mean, 11.8 +/- 2.8). T or placebo (P) was taken for 10 days in a double-blind, crossover controlled trial. During Nights 9 and 10 of each study period, the subjects slept in a sleep laboratory, where complete polysomnographs were recorded. Patients were subdivided according to T blood levels above or below 10 micrograms/ml: five children had a mean serum T of 11.7 +/- 1.6 micrograms/ml (Group 1), and seven patients had serum T levels of 6.7 +/- 1.5 micrograms/ml (Group 2). There was no difference in pulmonary function between the two periods, but Group 2 had significantly better baseline lung function (p less than 0.01). During sleep while on T, Group 1 had a higher mean SaO2 (93.1 +/- 0.3% T versus 90.7 +/- 0.3% P; p less than 0.0001), less time with a decrease greater than 5% in SaO2 from baseline (43.7 +/- 7.9 min T versus 85.8 +/- 7.9 min P; p less than 0.01), and a lower heart rate (HR), (77.9 +/- 5.1 bpm T versus 86.1 +/- 4.2 bpm P; p less than 0.01). Group 2 did not show differences in these parameters. T significantly disrupted sleep as measured by sleep efficiency and total wake time independently of serum level (p less than 0.01). There was no significant effect of T on the incidence of apnea, hypopnea, or body movements during sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741535 TI - Effects of theophylline on canine diaphragmatic contractility and fatigue. AB - To distinguish the effects of theophylline on respiratory muscle contractility from alterations in respiratory muscle interaction or blood flow, we examined in vitro contractile properties and fatigue of canine diaphragm in two series of experiments. In the first series, a 40-mg/kg aminophylline infusion was given to dogs, and diaphragm strips were removed for in vitro study when stable tissue fixation of the drug was reached. Compared with control bundles examined before aminophylline infusion, no alterations in twitch tension, tetanic tension, or force-frequency characteristics were observed. Moreover, theophylline-treated strips fatigued faster than control strips, whether subjected to repetitive submaximal or maximal contractions (p less than 0.01). In the second series, diaphragm bundles were equilibrated with high theophylline doses (400 mg/L) in vitro, and inotropic effects compared with the results in the first series. Supratherapeutic theophylline concentrations increased force development at low stimulation frequencies (p less than 0.05 at 10 Hz) and significantly elevated twitch-tetanus ratio (p less than 0.01) but did not protect against development of in vitro muscle fatigue. Poor penetration of theophylline in diaphragm bundles in vitro was excluded, since drug concentrations in the muscle bundle and the muscle bath were virtually equal. We conclude that diaphragmatic tissue concentrations correlate well with therapeutic serum and supratherapeutic bath levels and that only high theophylline concentrations increase canine diaphragmatic contractility in vitro. None of the theophylline concentrations studied could protect diaphragm bundles against the development of low- or high frequency fatigue in vitro. PMID- 1741536 TI - Diagnosis of sleep-disordered breathing by half-night polysomnography. AB - We hypothesized that sleep-disordered breathing (SDB), defined by the apnea index (AI), the apnea + hypopnea index (A + H/I), or the desaturation event frequency (number of desaturations greater than 5%/h slept) (DEF), could be diagnosed after less than full-night polysomnography (PSG). Forty-eight consecutive full-night PSG sessions were evaluated by separately analyzing the first half (PSG-1/2) and the total (PSG-T) sleep time: 134.42 +/- 35.7 and 277.15 +/- 56.5 min (mean +/- SD), respectively. PSG-1/2 and PSG-T were not different with respect to AI. The DEF was statistically but not clinically higher during PSG-1/2 (41.72 +/- 41 versus 37.95 +/- 35.8, p = 0.04). Sensitivities, specificities, and predictive values of each PSG-1/2 parameter were determined by comparing the values with those measured during PSG-T, using cutoff frequencies of both 5 and 10 events/h slept to define SDB. At a cutoff frequency of 10, sensitivities and positive predictive values were high for all PSG-1/2 parameters (range, 94.6 to 96.9%). The specificities of the DEF and AI during PSG-1/2 were also high (93.75 and 95%, respectively), but the negative predictive value of the DEF was substantially better (93.75 versus 83.3%). With SDB defined by 5 events/h slept, there also were high sensitivities (87.9 to 93%), positive predictive values (93.6 to 100%), and specificities (86.7 to 100%) for all parameters. Negative predictive values, however, were substantially reduced (62.5 to 76.5%). We conclude that PSG during 2 h of sleep is an appropriate method for evaluating SDB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741537 TI - Time course and calcium dependence of sustained bronchoconstriction induced by deep inhalation in asthma. AB - We studied six asthmatic patients who showed a progressive decrease in FEV1 when successive forced expiratory maneuvers were performed at 1-min intervals. We determined the time course of changes in specific airway conductance following a single deep inhalation (DI) and the ratio of maximum expiratory flow at 40% of FVC from maximal and partial flow-volume curves (MEF40M/P) during a series of forced expiratory maneuvers. Specific airway conductance measured 3 s after DI was increased by 11 +/- 6 (SE)%, which was not significantly different from an increase of 23 +/- 8% observed in six healthy control subjects. Later (i.e., 10 to 40 s after DI) specific airway conductance was significantly less than the pre DI value in asthmatic but not in healthy subjects. Mean FEV1 decreased significantly by 28% from the first to the eighth forced expiratory maneuver performed during a period of 15 min, whereas MEF40M/P was not significantly changed and remained always significantly greater than 1. The voltage-dependent calcium channel antagonist nifedipine significantly prevented the reduction of FEV1 without affecting MEF40M/P. We conclude that, in some asthmatic individuals, DI may induce a transient bronchodilatation followed by a calcium-dependent sustained bronchoconstriction. We suggest that the initial bronchodilatation is due to the mechanical interdependence between airways and lung parenchyma, whereas the sustained bronchoconstriction is due to contraction of the airway smooth muscle. PMID- 1741538 TI - Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge. Characterization of eosinophil and mast cell mediators. AB - Segmental antigen bronchoprovocation was used to define the nature of the inflammatory process in allergic airway disease. Bronchoalveolar lavage fluid obtained from allergic rhinitis patients 12 min after segmental antigen instillation (immediate response) revealed a significant increase in histamine and tryptase, but no cellular response. Repeat segmental lavage 48 h later (late response) showed marked and significant increases in both low and normal density eosinophils as well as striking elevations of eosinophil granular protein levels (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase). Leukotriene C4, but not tryptase, concentrations were also consistently elevated in late lavage samples. Further, the late lavage samples showed a significant increase in interleukin-5 concentrations that correlated with the presence of eosinophils and eosinophil granular proteins. Neither eosinophils nor soluble mediators of eosinophils increased when normal subjects were similarly challenged with antigen. These data suggest that eosinophils are attracted to the airway during the late-phase allergic reaction and that IL-5 may produce changes in airway eosinophil density and promote the release of granular proteins to cause airway injury. PMID- 1741539 TI - Increased numbers of mast cells in bronchial mucosa after the late-phase asthmatic response to allergen. AB - We examined the characteristics of allergen-induced inflammation of the bronchial mucosa in asthmatic patients. Studies were carried out 4 h (eight patients) and 24 h (nine patients) after allergen inhalation challenge; 10 patients were not challenged and served as control subjects. We found that in the control group the ratio of degranulating to granulated mast cells was higher in patients with than in patients without late-phase response. In patients studied 4 h after allergen challenge the total number of mast cells was not significantly different from that in control subjects; the ratio of degranulating to granulated mast cells was increased similarly in patients with and without late-phase response. Among patients studied 24 h after allergen challenge, those who had developed the late phase response had an increased (p less than 0.05) number of mast cells as compared with patients who had not developed the late-phase response, the number of mast cells was significantly correlated with the severity of the late-phase response (r = 0.80; p less than 0.001). The numbers of eosinophils and mononuclear cells and the morphologic abnormalities of bronchial structure (altered ratio of cylindrical to goblet cells, thickening of the basement membrane, and edema and angiectasis of lamina propria) were similar in the different groups of patients. We conclude that the inflammatory events leading to the development of the late-phase asthmatic response to allergen represent a stimulus for an increase in the number of mast cells in the bronchial mucosa. PMID- 1741540 TI - The effect of antioxidants on ozone-induced airway hyperresponsiveness in dogs. AB - The role of oxygen radicals in causing ozone-induced airway hyperresponsiveness in dogs was examined by pretreating dogs with allopurinol and/or deferoxamine mesylate (desferal), which are inhibitors of oxygen radical generation, before ozone inhalation. Acetylcholine airway responsiveness was measured before and after either air or ozone inhalation (3 ppm for 20 min) on 5 experimental days separated by at least 2 wk. On each day, the dogs were pretreated intravenously with allopurinol (50 mg/kg) followed by inhaled desferal (1,000 mg inhalation) or with allopurinol followed by the diluent for desferal or with the diluent for allopurinol and desferal or with both diluents. The effect of ozone on acetylcholine airway responsiveness was expressed as the differences in the log transformed preozone-postozone acetylcholine provocative concentrations. When dogs received both diluents or either treatment alone, ozone inhalation caused airway hyperresponsiveness. The mean log differences for the preozone-postozone acetylcholine provocative concentration were 0.804 (SEM, 0.17) for both diluents, 0.524 (SEM, 0.16) for allopurinol alone, and 0.407 (SEM, 0.22) for desferal alone. However, the combination of allopurinol and desferal significantly inhibited the development of ozone-induced airway hyperresponsiveness, the log difference being 0.195 (SEM, 0.11) (p less than 0.05), without inhibiting ozone induced neutrophil influx into the airways. The results suggest that the production of oxygen radicals is important in the pathogenesis of ozone-induced airway hyperresponsiveness. PMID- 1741541 TI - Lipid mediators contribute to oxygen-radical-induced airway responses in sheep. AB - The purpose of this study was to determine if the bronchoconstriction and airway hyperresponsiveness (AHR) resulting from aerosolized xanthine (x; 0.1%)-xanthine oxidase (xo; 4.1 U) and the subsequent production of oxygen radicals is mediated by the secondary generation of lipid mediators. In seven conscious sheep, specific lung resistance (SRL) was measured before and after x-xo challenge; approximately 30 min later when SRL had returned to baseline, airway responsiveness to carbachol was determined from dose-response curves by calculating the cumulative provocating dose of carbachol in breath units (BU, defined as one breath of a 1% wt/vol carbachol solution) that increased SRL 400% over baseline (PD400). Inhaled x-xo caused in immediate increase in SRL of 162 +/ 36% (mean +/- SE; p less than 0.05) over baseline and decreased PD400 from a baseline value of 32.5 +/- 5.0 to 16.6 +/- 1.7 BU (p less than 0.05). Pretreatment with the H2O2 scavenger, catalase (CAT,; 38 mg aerosol), methylprednisolone succinate (MS; 1 mg/kg given intravenously), the cyclooxygenase inhibitor, indomethacin (IND; 2 mg/kg given intravenously), and the PAF antagonist, WEB-2086 (3 mg/kg given intravenously) all attenuated the x xo-induced increase in SRL (p less than 0.05); the leukotriene D4 antagonist, MK 571 (5 mg by aerosol) had no effect. All agents inhibited the x-xo-induced decrease in PD400: mean BUs were 27 after CAT, 32 after WEB-2086, 34 after IND, 31 after MS, and 25 after MK-571 (all p less than 0.05 versus x-xo alone).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741542 TI - Interacting effects of atopy and bronchial hyperresponsiveness on the annual decline in lung function and the exacerbation rate in asthma. AB - The relationship between atopy and bronchial hyperresponsiveness (BHR) on the one hand and the annual rate of decline in FEV1 and the annual exacerbation rate on the other was studied in 71 adult patients with asthma during a period of 2 yr. Atopy (based on seven RAST tests) and BHR (PC20-histamine) were assessed at the start of the 2-yr follow-up period, and they were related to the decline in FEV1 (FEV1 slope) and the exacerbation rate. The results indicated that BHR was related to the FEV1 slope independently of the FEV1 level. The mean prebronchodilator FEV1 slope was -94 ml/yr (-39 to -149 ml/yr) in patients with PC20 less than or equal to 2 mg/ml and -21 ml/yr (+34 to -76 ml/yr) in patients with PC20 greater than 2 mg/ml. Atopy alone was not related to the FEV1 slope. However, in atopic patients BHR was related to a more pronounced FEV1 slope than in nonatopic patients. The slope of the postbronchodilator FEV1 was comparable with the slope of the prebronchodilator FEV1, which may indicate that the loss of FEV1 was not only due to increased bronchospasm but also to fixed obstruction. BHR and atopy were not associated with the exacerbation rate. Asthmatic patients with atopy and marked BHR should be looked upon as patients with a risk of developing progressive airflow obstruction. PMID- 1741543 TI - Evaluation of chronic bronchitis, chronic obstructive pulmonary disease, and ventilatory function among workers exposed to 2,3,7,8-tetrachlorodibenzo-p dioxin. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is produced as an undesirable contaminant in the manufacture of 2,4,5-trichlorophenol (TCP) and its derivatives. There is considerable concern about the health effects that may be associated with exposure to TCDD-contaminated substances. A cross-sectional medical study that included a comprehensive medical history, medical examination, and measurement of pulmonary function was conducted on workers employed more than 15 yr earlier in the manufacture of NaTCP and its derivatives at two chemical plants. The workers had substantial exposure to substances contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted, of 200 ppt compared with a mean of 7 ppt in the unexposed reference group. The comparison group consisted of individuals with no occupational exposure to phenoxy herbicides who lived in the same communities as the workers. A total of 281 workers and 260 unexposed referents participated in the medical examination. Logistic and linear regression analyses, which contained categorical and continuous measures of TCDD exposure, were performed to control for important confounders, including cigarette and alcohol consumption. No difference was found between workers and referents in the risk for chronic bronchitis or COPD. Analysis of the ventilatory function data revealed no association between history of exposure to substances contaminated with TCDD and the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or the ratio of FEV1 to FVC (FEV1/FVC%). PMID- 1741544 TI - Grain dust and lung function. Dose-response relationships. AB - Grain dust exposure has been associated with both acute and chronic respiratory abnormalities. We sought to answer two questions with regard to this exposure: (1) is there a dose-response relationship between grain dust and respiratory abnormalities, and (2) is there evidence to suggest that the allowable exposure (currently 10 mg/m3 in Canada) be lowered? We compared respiratory symptoms and lung function among 454 grain elevator workers and 55 civic workers to estimates of lifetime average grain dust exposure. A total of 781 personal air samples representing 20 different job titles over a 15-yr period were used to construct a job title-time period matrix for average dust exposure levels. The matrix was applied to each worker's detailed job history to obtain a value for estimated cumulative and average dust exposure. Significant dose-response relationships were seen for chronic phlegm production, breathlessness on exertion, FEV1, and FVC; and dose-response trends were evident for the longitudinal change in both FEV1 and FVC. Workers with estimated average exposure between 4 and 9 mg/m3 were found to have significantly lower values for FEV1 and FVC compared to both grain workers exposed to less than 4 mg/m3 on average and civic workers, despite no difference in duration of employment among these groups. The results indicate a strong dose-response relationship between grain dust exposure and both respiratory symptoms and lung function and also suggest that the current Canadian allowable exposure level of 10 mg/m3 is too high. PMID- 1741545 TI - Correlation of clinical and immunologic parameters of the inflammatory activity of pulmonary sarcoidosis. AB - The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena. PMID- 1741546 TI - Bronchoalveolar lavage cell data in alveolar proteinosis. AB - In bronchoalveolar lavage fluid (BAL) from nine patients with alveolar proteinosis (AP), total and differential cell count and T-lymphocyte phenotyping were done and compared with those in 12 healthy volunteers comparable as to age and tobacco consumption. Although total cell count was not significantly different from that in control subjects, the most prominent feature in patients was an increase in the number of CD4 and CD8 T-lymphocytes within the alveoli. Conversely, the macrophage population was significantly reduced. The ratio of CD4/CD8 T-lymphocytes tended to be high, but this increase did not reach statistical significance. The pathophysiologic mechanism and the meaning of these alveolar cell changes in AP remain to be elucidated. PMID- 1741547 TI - Increased lung clearance of 99mTcDTPA in allograft lung rejection. The Paris-Sud Lung Transplant Group. AB - To investigate whether lung 99mTc-DTPA clearance is altered during allograft lung rejection, a group of four double lung and 24 heart-lung transplant patients was studied using serial measurement of the clearance rate of aerosolized 99mTc-DTPA (DTPA-Cl), in association with pulmonary function tests, bronchoalveolar lavage, and transbronchial lung biopsies. Using histologic diagnosis as a standard, we compared 56 episodes with normal lung histology to 32 episodes with allograft lung rejection. A control group of 20 healthy nonsmokers was used to define normal DTPA-Cl. In patients with normal lung histology, DTPA-Cl was higher than in control subjects (2.62 +/- 0.25 versus 1.20 +/- 0.12 %/min; p less than 0.001). In the episodes of allograft lung rejection, DTPA-Cl increased to 3.65 +/ 0.41 %/min (p less than 0.02) as compared with episodes of normal lung histology. The change in DTPA-Cl during allograft lung rejection was correlated (r = 0.3, p less than 0.01) with the increased percentage of lymphocytes in bronchoalveolar lavage (27.8 +/- 3.5% in rejection versus 19.9 +/- 2.2% in normal histology; p less than 0.02). Sensitivity and specificity of DTPA-Cl measurement in detecting lung rejection were 69 and 82%, respectively, versus 45 and 85% for FEV1 measurement. These results suggest that DTPA-Cl monitoring could be used in conjunction with pulmonary function testing as a noninvasive approach for the detection of lung rejection. PMID- 1741548 TI - Role of platelet-activating factor in mediating tumor necrosis factor alpha induced pulmonary vasoconstriction and plasma-lymph protein transport. AB - We assessed the role of platelet-activating factor (PAF) in mediating the pulmonary hemodynamic and lymph flow responses to tumor necrosis factor-alpha (TNF alpha). The effects of the PAF receptor antagonist WEB 2086 on TNF alpha induced pulmonary vasoconstriction and increased pulmonary transvascular plasma lymph protein transport were examined. Control (n = 7) and WEB-2086-pretreated (n = 7) sheep prepared with chronic lung lymph fistulas were challenged with recombinant human TNF alpha (12 micrograms/kg over 0.5 h). Ex vivo challenge of platelet-rich plasma (PRP) with 10(-8) M PAF resulted in aggregation of platelets from control TNF-challenged sheep, but not of platelets from WEB-treated sheep similarly challenged with TNF. The control TNF-alpha-challenged sheep developed hemoconcentration, leukopenia, and neutropenia. TNF alpha resulted in increases in pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) within 15 min, and the values were sustained for the 5-h experiment duration. Pulmonary lymph flow (Qlym) and pulmonary transvascular protein clearance rate (Qlym x lymph-to-plasma protein concentration) were increased within 30 min and remained elevated for 5 h. The WEB-2086-treated sheep developed similar leukopenia and neutropenia after TNF alpha challenge, but the initial increases in Ppa and PVR were significantly reduced (p less than 0.05). However, WEB 2086 did not prevent the threefold increases in Qlym and transvascular protein clearance induced with TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741549 TI - Isoniazid preventive therapy for tuberculosis. Decision analysis considering ethnicity and gender. AB - The decision to prescribe or withhold isoniazid (INH) preventive therapy for low risk tuberculin reactors has been highly controversial, primarily due to isoniazid's possible hepatotoxic effects. Previous analyses have explored the INH decision only from the perspective of patient age, recognizing that the risks of INH-induced hepatotoxicity are age related. Decision analyses presented in this paper assess the impact of gender and ethnic group, as well as age, on the INH decision. Results for low-risk patients favor prescribing INH preventive therapy for all 20-yr-olds, all 35-yr-olds except black women, and no 50-yr-olds, projecting life expectancy benefits that range from 3 to 19 days. A comparison set of analyses performed for high-risk patients favors prescribing INH for all groups except 50-yr-old black women. These findings suggest that ethnicity, gender, and age should be considered when making the decision to prescribe or withhold INH preventive therapy. PMID- 1741550 TI - Detection of human T-cell lymphotropic virus type I-related antibodies in patients with lymphocytic interstitial pneumonia. AB - Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial pneumonia with infiltration of mononuclear cells in the interstitium, the pathogenesis of which is unknown. We studied six patients with LIP to investigate the immunologic characteristics of lymphocytes in the lower respiratory tract and the possible involvement of human T-cell lymphotropic virus type I (HTLV-I), which is endemic in the southwestern region of Japan. Lymphocyte surface antigen phenotyping in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) cells revealed a predominance of CD8 positive (suppressor/cytotoxic) T-lymphocytes (PB: 51.5 +/- 0.8%; BALF: 52.9 +/- 12.7%), which consisted of an increased number of CD8 positive CD11 negative (cytotoxic) T-lymphocytes (PB: 30.2 +/- 10.5%; BALF: 57.1 +/- 11.8%). The increased number of cytotoxic T-lymphocytes among patients with LIP led us to investigate the possible involvement of HTLV-I, EB virus, and HIV in patients with chronic interstitial disorders of LIP, sarcoidosis, and IPF. The seropositivity rate for HTLV-I was 83.7% (5/6) in patients with LIP, 3.1% (1/28) with IPF, 7.1% (2/28) with sarcoidosis, and 0% (0/28) in healthy volunteers. None of the patients were seropositive for either HIV or EB virus. These results suggest that HTLV-I may be involved in a direct or indirect role in the pathologic mechanisms through the host immune reaction to the antigenicity of the virus and/or the possible involvement of viral regulatory genes to disrupt the normal immune reaction of the host. PMID- 1741551 TI - Immunohistopathology of murine pulmonary histoplasmosis during normal and hypersensitive conditions. AB - Pulmonary histoplasmosis was induced in nonimmunized and immunized Balb-C nu/+ mice. The lung tissue burden of H. capsulatum, histopathology, the size of the inflammatory area, and the numbers of total T lymphocytes and subtypes in situ were evaluated serially after challenge. Over 3 days previously immunized mice developed a large lymphocyte/macrophage inflammatory response. This rapidly decreased in the next 2 wk. In contrast, the nonimmunized control mice developed a predominantly polymorphonuclear infiltrate that evolved more slowly over the first week of infection. This initial response was nonspecific but, after the first week, shifted to lymphocytes and granuloma formation. The lymphocyte infiltration in both immunized and nonimmunized mice was predominantly CD4. Previously immunized mice had a rapid decrease in tissue counts of H. capsulatum after Day 3, but nonimmunized mice continued to have increased counts through Day 7 after infection. These studies reproduce in the mouse model a host response similar to acute reinfection histoplasmosis in the human. In this condition an intense cell-mediated inflammatory response is thought to be elicited by fungal antigens and to represent host reaction rather than fungal replication. Our experimental model added new information relevant to the understanding of the pathogenesis of this process. PMID- 1741552 TI - Surfactant protein A, phosphatidylcholine, and surfactant inhibitors in epithelial lining fluid. Correlation with surface activity, severity of respiratory distress syndrome, and outcome in small premature infants. AB - Although surfactant deficiency at birth is the major cause of respiratory distress syndrome (RDS), there is insufficient data on surfactant and surfactant inhibitors after birth. In the present study, a total of 345 airway specimens (AS) from 61 neonates of gestational age of 24 to 29 wk (54 with RDS) were analyzed for concentrations of phosphatidylcholine (PC), saturated PC (SPC), surfactant protein A (SP-A), nonsedimentable protein, and free amino acids in epithelial lining fluid (ELF). The relationship between surfactant indices, surface activity, and severity of RDS was studied. Treatment with human surfactant containing SP-A increased [PC]ELF and [SPC]ELF to levels found in infants without RDS. In placebo-treated infants similar concentrations were first reached between Days 4 and 7. Surfactant treatment increased the low SP-A/SPC ratio, although this ratio remained lower than that in exogenous surfactant. In RDS, the concentrations of free amino acids in ELF were 6 to 31 times higher than in infants without RDS. The nonsedimentable proteins of AS and cationic amino acids increased the minimum surface tension of SP-A-deficient surfactant from AS. Addition of SP-A improved the surface activity. According to multiple regression analysis, In [PC]ELF (p less than 0.0001), SPC/PC ratio (p less than 0.0001), In SP-A/SPC ratio (p less than 0.0002), and [protein]ELF (p less than 0.01) correlated with alveolar-arterial oxygen pressure gradient. Of the infants weighing less than 1,000 g, those who were going to die or develop bronchopulmonary dysplasia had a strikingly lower SP-A/SPC ratio during the first week (less than 25 ng/nmol) than those surviving without BPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741553 TI - Centrilobular and panlobular emphysema in smokers. Two distinct morphologic and functional entities. AB - In order to investigate the hypothesis that different morphologic patterns of disease might correspond to different mechanical properties of the lung in emphysema, pulmonary function tests and lung mechanics were measured in 34 subjects undergoing lung resection for peripheral lung tumors. Using standard microscopic criteria, pure or predominant centrilobular (n = 18) or panlobular (n = 16) emphysema was diagnosed in lungs. The degree of emphysema measured by the mean linear intercept (Lm) was not significantly different between the two groups. However, the coefficient of variation of the interalveolar wall distance (CV) was significantly higher for the same Lm in CLE than in PLE. This indicates that CLE has an uneven pattern of destruction, whereas PLE is more homogeneous. CLE had a higher degree of abnormalities in the small airways (SAD) than did PLE (p less than 0.05) mainly because of significantly higher muscle score (p less than 0.001) and fibrosis. CLE also had a higher proportion of airways less than 400 microns in diameter than did PLE (p less than 0.05). Static compliance, specific compliance, and the exponential constant (K) were significantly lower (p less than 0.005, p less than 0.001, and p less than 0.05, respectively) in CLE than in PLE. FEV1/FVC was significantly correlated with SAD in CLE (r = -0.69, p less than 0.01) but not in PLE (r = 0.29 p greater than 0.05); conversely, FEV1/FVC was significantly correlated with elasticity (K) in PLE (r = -0.72, p less than 0.01) but not in CLE (r = 0.08, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741554 TI - Neuropeptides in the respiratory tract. Part II. PMID- 1741555 TI - Columnar papilloma of the bronchus. Case report and literature review. AB - Solitary papillomas are rare endobronchial neoplasms that are most commonly lined by a squamous epithelium (i.e., squamous papillomas). Papillomas exhibiting nonsquamous epithelium are even more unusual; only seven solitary papillomas lined by columnar epithelium (i.e., columnar papillomas) have been previously described. The current report presents the eighth patient with a columnar papilloma and demonstrates some features common to solitary papillomas (i.e., central location in the airways, associated atelectasis), but distinctive from squamous papillomas (i.e., absence of malignant potential). PMID- 1741556 TI - Hyperthyroidism induced by iodinated glycerol. AB - We report a case of iodide-induced thyrotoxicosis after the use of iodinated glycerol (Organidin) for the symptomatic treatment of chronic obstructive pulmonary disease. In patients with severe chronic obstructive pulmonary disease, symptoms of hyperthyroidism may be overlooked. Hyperthyroidism may be induced by any iodinated expectorant, especially in patients with preexisting thyroid disease. PMID- 1741557 TI - Evaluation of the float sign for determining adequacy of specimens obtained with transbronchial biopsy. AB - This study prospectively evaluated the alveolar content of transbronchial biopsy specimens based on whether or not they floated in formalin. One hundred biopsy specimens were obtained from 18 patients. Specimens with any alveoli were significantly more likely to float (45 of 61, 74%) than those with no alveolar tissue (15 of 39, 39%; p less than 0.001). The majority of diagnostic specimens were obtained in eight patients with sarcoidosis, where 47 biopsies were obtained. Fourteen of 19 specimens (74%) with noncaseating granulomas floated, whereas only 11 of 28 (39%; p less than 0.05) nondiagnostic specimens floated. The results of this study suggest that this simple bedside observation may serve to determine the adequacy of transbronchial biopsy specimens, particularly in sarcoidosis. PMID- 1741558 TI - Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease. AB - TWAR, the only known serovar of Chlamydia pneumoniae, is a newly described bacterium that has been identified as a cause of both epidemics and endemic cases of pneumonia. The role of TWAR infection in patients with chronic obstructive pulmonary disease (COPD) is not known. We conducted a prospective study to establish whether TWAR infection is a common cause of acute exacerbations of COPD. We studied two groups of patients: 44 patients admitted to the hospital with acute exacerbations of COPD, and 65 stable clinic patients with COPD. We found that evidence of acute TWAR infection was infrequent in patients with exacerbations (5%). In contrast, the majority of patients from both groups had serologic evidence of previous TWAR infection (77%). This was not significantly greater than the prevalence found in a small group of patients of similar age and sex without lung disease from the same institution (73%). TWAR was not isolated from the oropharyngeal specimens obtained from 97 subjects, suggesting that it does not colonize the respiratory tract of patients with COPD. This study shows that at the time of low incidence in the community, acute TWAR infection is uncommon in patients with acute exacerbations of COPD. The majority of patients with COPD have, however, been infected with TWAR in the past. The clinical manifestations of these infections are not known and should be the focus of further studies. PMID- 1741559 TI - NHLBI workshop summary. Hyperbaric oxygenation therapy. PMID- 1741560 TI - Do patients with obstructive sleep apnea have thick necks? PMID- 1741561 TI - Chronic airflow limitation in South African gold miners. PMID- 1741562 TI - [Maternal-fetal integration of thyroid hormones]. PMID- 1741563 TI - [Concept and therapeutic management of precocious puberty]. PMID- 1741564 TI - [Immunology of diabetes]. PMID- 1741565 TI - [Immunology of diabetes. Pathogenic bases]. PMID- 1741566 TI - [Immunology of diabetes. Immunologic markers]. PMID- 1741567 TI - [Molecular analysis of the androgen receptor gene in androgen resistance syndrome]. PMID- 1741568 TI - [Classification of infantile acute non-lymphoblastic leukemia and prognostic correlations]. PMID- 1741569 TI - [Medical audit of the clinical history of the infantile population treated at a primary care facility]. AB - Authors present qualitative and quantitative results of a health quality assurance study of pediatric population in primary care. Ten criteria were accepted by consensus and level of 90% of fulfilling was taken as optimal standard. None of the criteria reached that level. The best fulfilled ones were those referring to pregnancy (89%), vaccination (87.7%), lactancy (87%), weight at birth (86.7%), parturition (84%) and newborn period (82%). Among qualitative results most remarkable were vaccination coverage (95.7%), length of breast feeding (1-3 months, 60.6%) and untimely introduction of cereals with gluten (35.4%) and full-fat cow milk (50.3%). Authors consider that this kind of study is useful in primary care centers. It is necessary to include health care quality assurance activities among basic goals of these centers. PMID- 1741570 TI - [Evolution of the treatment of acute nonlymphoblastic leukemias in children (1968 1990)]. AB - Changes in treatment of ANLL in children over 23 years (1968-90) and advances made in the last ten years in a pediatric hematological unit are reported herein. Of 124 patients under 15 years of age, 18 of whom were infants, 118 were evaluable. Of these, 58 were treated before 1980 and, although complete remission (CR) was attained in 75%, the median duration was lower than 12 months and no patient survived in CR more than 6 years. From 1981 to 1987, 40 patients received one or two induction treatments followed by three consolidations and then blocks of sequential intensive chemotherapy for 12-15 months. CR was attained in 87.5% and event-free survival (EFS) was 22.5% at 8 years: 14% for those treated from 1981 to 1983 and 33% for those included in the ANLL-84 protocol. In 1988, a post remission protocol with intensification therapy (two high-dose ARA-C treatments combined with mitoxantrone in the first and amsacrine in the second) followed by allogeneic or autologous bone marrow transplant (BMT) was initiated. Of 20 patients included, 17 reached CR (85%) and 16 underwent BMT. EFS of the 20 patients was 65% at 2 years and post-BMT relapse-free survival was 75%. These results are compared with those obtained separately with present intensive chemotherapy protocols and with BMT and it is concluded that intensification treatment followed by BMT (allogeneic or autologous) might constitute an advance in the treatment of children with ANLL. PMID- 1741571 TI - [Spontaneous and GHRH-induced nocturnal GH secretion in a child population with insulin dependent diabetes mellitus]. AB - It has been studied integrated nocturnal secretion of GH after GHRH test in 15 diabetic children and 10 short stature children with normal GH secretion. The most important findings are: 1) The integrated nocturnal secretion of GH was significantly higher in diabetics than in controls (6.27 +/- 3.11 ngrs/ml/min versus 3.06 +/- 1.41 ngrs/ml/min P [symbol; see text] 0.01). 2) After an acute stimulous with GHRH, diabetic population shows an exaggerated secretion of G. H. during the first 90 minutes compared with control population (33.20 +/- 12.41 ngrs/ml/min versus 18.18 +/- 11.09 P [symbol; see text] 0.01). 3) Both higher spontaneous secretion of G. H., and after GHRH test, are independent of metabolic control (mean nocturnal glycemies and HBA1) and evolution time of disease. PMID- 1741572 TI - [Phosphorus-calcium metabolism in children under prolonged treatment with anticonvulsants. (II)]. AB - Comparative assessments were made regarding the effects of prolonged administration of anticonvulsant drugs (phenobarbital, carbamazepine, valproate and polytherapy) on the different biochemical parameters related to phosphocalcium metabolism, in 98 children between 1 and 14 years. The most patent effect was on the levels of 25-Hydroxycholecalciferol which went down significantly (p = 0.0001) in children treated with phenobarbital (34.5 +/- 17 ng/ml) or polytherapy (28.4 +/- 18 ng/ml) in relation to those treated with carbamazepine (49.2 +/- 15 ng/ml) or valproate (43.1 +/- 15 ng/ml) and to control group (45.9 +/- 13 ng/ml). The alkaline phosphatase has been found significantly higher among those treated with phenobarbital, carbamazepine and polytherapy, evidencing significant differences in relation to those treated with valproate and to control group (p less than 0.05). For calcium, parathyroid hormone and osteocalcine levels no differences were found in the different drugs, nor with control group. Depending on the duration of treatment there was a significant reduction (p = 0.02) in the levels of 25-Hydroxycholecalciferol in children treated over 3 years, but no difference for calcium, phosphorous, alkaline phosphatase and PTH under this parameter. PMID- 1741573 TI - [Celiac disease. Is its clinical pattern changing?]. AB - Celiac disease (CD) is one of the most malabsorption syndromes in Pediatrics, its diagnosis being based on peroral intestinal biopsy. During the period 1974-1988 we have studied 178 patients with the suspected diagnosis of CD: diagnosis was confirmed in 117 whereas 22 are still under study. Mean age of the patients was 22.5 +/- 22.7 months, diagnosis being made during the first year of life in 32.6% of cases. Most cases had a classic clinical onset, although over the last year symptoms seen to be less apparent. Several patients presented with atypical forms. Also, associated diseases are observed in several cases. CD is often presented nowadays with few or atypical symptoms of difficult diagnosis and in this context the use of immunologic markers may be specially helpful. PMID- 1741574 TI - [Adoption of HIV positive children. A rarely discussed subject requiring immediate solution]. AB - After programme a inquiry-type this carry out itself amongst the families that adopted children with antibodies from the human immunodeficiency virus (AcVIH) in, they communicate the facts collected about the problematic that raise their adoption. They provide some conclusions. PMID- 1741575 TI - [Coxalgia in adolescents: apropos of three different cases: chondrolysis, transient osteoporosis and epiphyseolysis]. AB - We report 3 adolescents presenting with hip pain. Idiopathic chondrolysis, transient osteoporosis and slipped epiphisis were the final diagnosis. Initial diagnosis may be difficult despite adequate investigation. In such cases long term follow-up is essential. This paper includes a differential diagnosis of hip problems in childhood. PMID- 1741576 TI - [Evaluation of the nutritional state in patients with congenital cardiopathy]. AB - Several anthropometrical, immunological and biochemical parameters have been utilized for the detection of chronic undernourishment and inflammation. The present work proposes a comparative study between a control group and other of 24 cardiac patients, with the intention of valuating their nutritional and inflammatory state. We have used the index proposed by Ingenbleek (PINI = prognostic inflammatory and nutritional index) in which nutritional scoreboards and biochemical inflammatories correlate. We find some statistically significant differences between cases and controls, both with regard to the value of the PINI, and with regard to each of this variables. In the same way, we do not find any important correlations within each group among the nutritional biochemical, inflammatory and anthropometrical parameters. The clinical impression shows that the classification by groups of risk obtained according to the value of the PINI is very near to reality. We consider that the PINI index is useful as a predictive and evolutive parameter, and it can be used in children with a chronic illness. PMID- 1741577 TI - [Aortic valva atresia with normal left ventricle and interventricular communication]. AB - We present three patients with aortic atresia, normal left ventricle and ventricular septal defect by bidimensional echocardiography. In two patients the Norwood's procedure was performed, but they died in the immediate postoperative time. The different procedures for the correction of this kind of aortic atresia and the necessity of prompt surgical treatment are discussed here. PMID- 1741578 TI - [Motor function of the esophagus following surgery for atresia]. AB - We have studied for periods averaging 111 months 16 survivors out of a series of 20 children treated for oesophageal atresia (EA) by neonatal end-to-end anastomosis. Twelve of them had gastroesophageal reflux (GER) manifested by either digestive (vomiting, dysphagia, pyrosis, haemorrhage or foreign body impaction) or respiratory symptoms (repeated neumoniae or frequent u.r.i.). pH studies decealed very increased acid exposure in these patients. Manometric studies showed disorganized peristalsis with near-absence of propulsive waves and predominance of mass-contractions. Interestingly both lower esophageal sphincter pressure and length were normal. Five children had histological esophagitis and 2 had Barrett's esophagus. Seven patients have had an anti-reflux procedure and two more should be operated in the near future. Our experience reveals that GER incidence in EA is very high, that esophageal function is severely impaired in this condition, that mucosal lesions can be serious and that funduplication is effective. Since it has been demonstrated that esophageal dysfunction in EA patients is due to structural anomalies, spontaneous improvement should not be expected in them and surgical treatment should be largely indicated. EA patients require long-term gastro-enterologic follow-up. PMID- 1741579 TI - [Acute renal insufficiency with IgE specific RAST induced by amoxicillin in a 9 month-old infant]. PMID- 1741580 TI - [Cervico-mediastinal lipoblastomatosis. Report of a case and review of the literature]. PMID- 1741581 TI - [Accidental ingestion of hydrocarbon and intravascular hemolysis: an infrequent complication]. PMID- 1741582 TI - [Massive thymus hyperplasia in infancy: current status of diagnostic and therapeutic technics. Apropos of a recent clinical case]. PMID- 1741583 TI - [Glycogenosis type III. New aspects in nutritional management]. PMID- 1741584 TI - Inositol trisphosphate/calcium-dependent acetylcholine release evoked by bradykinin in NG108-15 rodent hybrid cells. PMID- 1741585 TI - Changes in presynaptic function during long-term potentiation. PMID- 1741586 TI - Membrane fusion as seen in rapidly frozen secretory cells. PMID- 1741587 TI - Role of specific lipids and annexins in calcium-dependent membrane fusion. PMID- 1741588 TI - A dissection of steps leading to viral envelope protein-mediated membrane fusion. PMID- 1741589 TI - A lipid/protein complex hypothesis for exocytotic fusion pore formation. PMID- 1741590 TI - Millisecond studies of single membrane fusion events. PMID- 1741591 TI - The sea urchin cortical reaction. A model system for studying the final steps of calcium-triggered vesicle fusion. PMID- 1741592 TI - MPP+ enhances potassium-evoked striatal dopamine release through a omega conotoxin-insensitive, tetrodotoxin- and nimodipine-sensitive calcium-dependent mechanism. PMID- 1741593 TI - Subsecond kinetics of inositol 1,4,5-trisphosphate-induced calcium release reveal rapid potentiation and subsequent inactivation by calcium. PMID- 1741594 TI - The effect of low-energy combined AC and DC magnetic fields on articular cartilage metabolism. PMID- 1741595 TI - Developmental changes in the pharmacology of Ca(2+)-dependent neurotransmitter release. PMID- 1741596 TI - Stimulus-induced nuclear Ca2+ signals in fura-2-loaded amphibian neurons. PMID- 1741597 TI - The effect of omega-conotoxin GVIA on field potentials in the hippocampus and nucleus accumbens in vitro. PMID- 1741598 TI - Diazepam enhances Ca2+ levels in rat brain synaptosomes. PMID- 1741599 TI - Relationship between membrane depolarization and intracellular free calcium in individual nerve terminals from the neurohypophysis. PMID- 1741600 TI - Calcium- and barium-activated acetylcholine synthesis and release from isolated nerve terminals. Do divalent cations alter membrane potential? PMID- 1741601 TI - Long-term monitoring of depolarization-induced exocytosis from adrenal medullary chromaffin cells and pancreatic islet B cells using "perforated patch recording". AB - (1) Membrane capacitance measurements using perforated patch recording offer the possibility of studying the process of depolarization-secretion coupling (DSC) in single endocrine cells with unprecedented time resolution and stability. (2) Early results with catecholamine-secreting adrenal chromaffin cells and insulin secreting pancreatic B cells support longstanding ideas that the Ca(2+)-dependent processes underlying DSC are fundamentally similar to those of nerve terminals. (3) Future experiments using these approaches should prove useful in sorting out those effects of humoral substances that have a predominant effect on excitability and Ca2+ entry from those that affect the secretory process itself. PMID- 1741602 TI - Calcium dynamics in the presynaptic terminal of barnacle photoreceptors. PMID- 1741603 TI - A barium-dependent chromaffin granule aggregating protein from bovine adrenal medulla and other tissues. PMID- 1741604 TI - A five-year analysis of botulinum toxin type A injections: some unusual features. AB - We analyzed patients treated during the past five years with botulinum toxin type A for strabismus and blepharospasm, reviewed our successes, failures, and unusual cases, and drew conclusions based on these treatments. Thirty-seven percent of the strabismus patients were cured, but many patients who were outside the strict definitions, still believed that they were significantly improved. A prominent feature in the treatment of strabismus was variability. Frequently, patients expected to do poorly had encouraging results. One permanent overcorrection occurred, and it converted an esotopic patient into an exotropic one with diplopia. This has persisted for 2.5 years and is the longest reported overcorrection to our knowledge. Our results indicate that larger doses of botulinum toxin produce longer spasm-free intervals in the treatment of blepharospasm. One patient receiving injections for her blepharospasm discovered that its cause was her sedative medication. This is the first reported case of a benzodiazepine inducing blepharospasm to our knowledge. PMID- 1741605 TI - Neodymium:yttrium aluminum garnet laser anterior capsulotomy. AB - Anterior capsulotomy of the lens capsule is one of the important steps before extracapsular lens extraction. A neodymium:yttrium aluminum garnet laser anterior capsulotomy was done in 144 eyes with immature, mature, and hypermature senile cataracts. This noninvasive technique is a safe and useful way to treat immature cataracts. To achieve the best result, the time interval between laser capsulotomy and surgery should be within six hours. Flap types of capsulotomy give the best results. PMID- 1741606 TI - A consecutive ultrastructural study of action of homoharringtonine on fibroblasts in vitro. AB - The authors studied the effect of homoharringtonine (Hh), a semisynthetic Chinese herb, on the ultrastructure of in vitro cultured human conjunctival fibroblasts (HFb) and its mechanism of action. Preliminary results showed that the main characteristics of HFb damage caused by Hh were invagination of the nuclear membrane, aggregation and margination of chromatin, and massive vacuolization of the cytoplasm. In addition, Hh can inhibit the secretion of collagen fibers and the synthesis of microfilaments. Therefore, Hh might be an effective agent in the prevention and treatment of proliferative eye disorders. PMID- 1741607 TI - Fungal keratitis associated with contact lens wear after penetrating keratoplasty. AB - A 71-year-old patient had a stromal infiltration at the donor-recipient interface two years after penetrating keratoplasty while wearing a "piggyback-type" contact lens. The corneal graft sutures in the affected area had been removed one year previously. Corneal scraping revealed the presence of Candida parapsillosis, and the infection was treated successfully with a combination of amphotericin B and flucytosine. The association between contact-lens wear and fungal infections of corneal grafts is discussed. PMID- 1741608 TI - Iatrogenic lens rupture after a neodymium: yttrium aluminum garnet laser iridotomy attempt. AB - During the past decade, laser iridotomy has replaced surgery as first-line treatment in angle-closure glaucoma. Its simplicity, fewer and less severe complications, and speedy recovery was responsible for this. Usually, the more common side effects of laser iridotomy are either preventable or easily treatable. Reported lens changes are limited to localized nonprogressive opacities and an isolated case of lens dislocation. We report the rare instance of lens rupture after a neodymium: yttrium aluminum garnet laser iridotomy attempt. Proper patient selection, good techniques with cautious use of laser energy, and meticulous attention to detail should prevent this complication. PMID- 1741609 TI - Evaluation of drug treatments for proliferative vitreoretinopathy using vitreous microtensiometry. AB - The effectiveness of antimetabolic and anticollagen agents against proliferative vitreoretinopathy (PVR) was assessed by vitreous microtensiometry, a new technique that measures in situ the tensile strength of vitreous membranes. Two PVR models were produced in rabbits by intravitreal injection of bovine retinal pigment epithelial (RPE) or fibroblast cells, and the animals subsequently were treated with 5-fluorouracil (5-FU) and beta-aminopropionitrile (BAPN), administered alone or in combination. The fibroblast PVR model produced high strength membranes that did not respond significantly to these therapies. The RPE model gave lower-strength membranes that showed marginally significant decreases in strength with intravitreal 5-FU and systemic BAPN treatments. However, combination therapy showed a highly significant decrease in membrane strength and a clinically encouraging reduction in retinal detachment. PMID- 1741610 TI - Anterior scleral staphyloma associated with neurofibromatosis. AB - We report the case of a woman with neurofibromatosis and anterior scleral staphyloma. To the best of our knowledge, this type has not been reported previously. PMID- 1741611 TI - My kind of biology. PMID- 1741612 TI - Control of carbon and nitrogen metabolism in Bacillus subtilis. PMID- 1741613 TI - Polymerase chain reaction: applications in environmental microbiology. PMID- 1741614 TI - Putative virulence factors of Candida albicans. PMID- 1741615 TI - Regulation of human immunodeficiency virus replication. PMID- 1741616 TI - Viruses of the protozoa. PMID- 1741617 TI - Biochemical diversity of trichloroethylene metabolism. PMID- 1741618 TI - Plant genetic control of nodulation. PMID- 1741619 TI - Serine beta-lactamases and penicillin-binding proteins. PMID- 1741620 TI - Gene amplification in Leishmania. PMID- 1741621 TI - Ivermectin as an antiparasitic agent for use in humans. PMID- 1741622 TI - Mechanisms of natural resistance to human pathogenic fungi. AB - Natural host-resistance mechanisms are essential first-line defenses against most mycotic agents; however, these defenses are often not sufficient for complete protection. The host relies on the immune responses to provide the additional antifungal activity necessary for maximum protection. In systemic mycotic diseases, the immune system must be functional to prevent the host from succumbing to the disease. Natural resistance mechanisms act together in a coordinated manner early in the disease process to either kill or prevent the fungal agent from proliferating and gaining entrance to other tissues. The early defensive measures of the natural effector mechanisms are usually sufficiently effective to provide time for the generally more effective immune defenses to develop. Together, the natural defenses and the immune defenses regulate each other through cytokine networks, and generally these systems provide the host with adequate protection against threatening mycotic agents. PMID- 1741623 TI - Nuclear fusion in yeast. PMID- 1741624 TI - Prokaryotic osmoregulation: genetics and physiology. PMID- 1741625 TI - Genetically engineered baculoviruses as agents for pest control. PMID- 1741627 TI - The culture of nursing. PMID- 1741626 TI - Techniques for selection of industrially important microorganisms. AB - The screening of microorganisms for the production of useful products continues to be an important aspect of biotechnology. Although advances in instrumentation, genetics, and microbial physiology are having an impact, screening programs are still primarily based on so-called classical techniques of enrichment and mutagenesis. One area that needs strengthening is the advancement of knowledge in microbial physiology. Recent surveys indicate that industry leaders see trained microbial physiologists as being the limiting factor in development of biotechnology in the coming decade. The largest impediment to development of new screening techniques is the ironic lack of programs specifically directed at developing new techniques. Too much emphasis is placed on using available techniques and relying on sheer labor and screening of vast numbers of organisms to produce novel products. In this respect, the Japanese are the exception and have proven that the establishment of new programs is worth the cost and effort. They are undoubtedly the world leaders in development of screening techniques and consequently the discovery of novel products. The isolation of microbes from novel and extreme environments holds tremendous promise in two areas. First, as Omura (46) and others (9, 48, 65) state, novel organisms will yield novel products. Second, such organisms serve as models for the understanding of structure and function that will facilitate the genetic manipulation of organisms and advance our ability to engineer novel enzymes. Hopefully such advances will enable genetic and protein engineering to have a greater impact on screening programs and techniques in the future. The earth holds a vast amount of varied and unique environments, from natural extremes such as high-altitude deserts and thermal springs, to manmade environments such as industrial-waste-treatment facilities, from which, with the appropriate methods and techniques, we may isolate and evaluate new potential products. PMID- 1741628 TI - Nursing and medical care of primary dementia patients in a community hospital setting. AB - A group of 480 hospital discharges systematically drawn from elderly, community hospital discharges were examined in order to describe the hospitalization experiences of individuals with admitting or coexisting diagnoses of primary dementia. Demented patients (7.1% of the sample) were most likely to be among the oldest hospitalized elders. The most frequently recorded patient problem was "alteration in thought processes." Most nursing interventions emphasized safety precautions, often to the exclusion of psychosocial intervention to maximize and support the patient's level of cognitive functioning. Over one fourth of the demented patients had written "no code" prescriptions. Approximately 44% of the elders in the dementia subsample had prescriptions for psychotropic medications. PMID- 1741629 TI - The patient educator role in nursing. AB - A stratified random sample (N = 1,230) of staff nurses, nurse administrators, and nurse educators were surveyed for their perceptions of the extent of nurses' responsibility for patient education and of the level of achievement of patient education by nurses. It was found that all three groups rated nurses' responsibility for patient education at a high level. Although the staff nurse group had statistically significant lower ratings (p = .0005) for nurses' level of responsibility for patient education, all three groups rated nurses' responsibility above 4 on a 5-point scale, with 5 reflecting primary (highest) responsibility. However, achievement of patient education was rated by all three groups below 3, the "good" rating on a 5-point scale, with 5 reflecting an excellent rating. The findings of this study indicate that the role of the nurse as patient educator needs to be strengthened. The satisfactory achievement of patient education is essential for the advancement of the nurse's role as patient educator. PMID- 1741630 TI - Exercise as a health-promoting lifestyle choice. AB - The primary purpose of this exploratory study was to examine differences between exercisers and nonexercisers in self-esteem, perceived benefits of exercise, and perceived barriers to exercise. Second, we investigated how much variation in group membership as an exerciser or nonexerciser could be explained by the relationship among self-esteem, perceived benefits of exercise, and perceived barriers to exercise. A sample of 105 university students completed four questionnaires. Using t tests, a significant difference was found between exercisers and nonexercisers on self-esteem, perceived benefits of exercise, and perceived barriers to exercise. It was found that the three variables successfully accounted for 32% of the variation in group membership as an exerciser or nonexerciser. PMID- 1741631 TI - Resource use in home care agencies. AB - Increasing use of home care services in the past decade has led to concern about the nature and number of services provided to clients. Because third party payers have used case mix measures to develop reimbursement systems for acute and long term care facilities, it seems likely that similar measures will be developed for home care. Three types of home care agencies were studied to test the usefulness of routinely gathered clinical and financial data for predicting resources provided. The findings suggest that current data sources may be inadequate for predicting the actual delivery of services. PMID- 1741632 TI - Family coping: a comparison of stepfamilies and traditional nuclear families during pregnancy. PMID- 1741633 TI - Nursing research instruments: pathway to resources. AB - Measurement of nursing phenomena involves locating and obtaining instruments that are reliable, valid, and feasible for use with an intended sample. Beginning with a clear conceptualization of the problem and delineation of the measurement framework, the process of finding and legally obtaining and using appropriate instruments can proceed. Resources for instruments are so numerous today that it is especially important to insure that valuable resources are not overlooked. Computerized resources offer comprehensive and efficient searches at low cost. The persistent nurse researcher who is aware of how to find and use the many resources available can select from among the numerous alternatives to measure nursing phenomena. The U.S. Copyright Act of 1976 has been shaped over the years by court cases and committee work to protect original work, including nursing research instruments. Knowledge of the provisions of copyright law may minimize the danger of unintentional violation while obtaining research instruments. PMID- 1741634 TI - BARRIERS: the barriers to research utilization scale. PMID- 1741635 TI - Incorporating research role and practice role. PMID- 1741636 TI - Nurse managers: role expectations and job satisfaction. AB - The purpose of the study was to assess the relationships among nurse managers' perceived job stress/job satisfaction, time allocation, and role expectations. The dependent variable was job satisfaction. The sample consisted of 72 nurse managers who responded to a self-administered questionnaire. It was found that nursing supervisors are satisfied with the actual time allocation of nurse managers, whereas physicians and nursing staff believe that more of the nurse managers' time should be given to direct patient care. When discrepancies occur about the allocation of nurse manager time, the nurse manager is apt to have lower job satisfaction. PMID- 1741637 TI - Facilitating clinical research: nurse-to-nurse support. PMID- 1741638 TI - Fatigue in postpartum women. AB - Childbirth and the responsibilities of parenting after birth require a great deal of energy. Fatigue in postpartum women is a concern for maternal-child nurses because of the impact on the health and parenting ability of the mother. To determine fatigue levels and types, 35 women who vaginally delivered were surveyed at 2 days, 2 weeks, and 6 weeks postpartum. This sample was found to be mildly fatigued, with situational and/or psychological fatigue. Nurses can intervene by assessing postpartum fatigue and using teaching/counseling methods for knowledge preparation and for clients at risk. PMID- 1741639 TI - Effects of caffeinated coffee on intraocular pressure. AB - This study examined the effects of caffeinated coffee on the intraocular pressure of nonglaucomatous subjects. Subjects were randomly assigned to receive each of three treatments: caffeinated coffee, hot water, and no fluid. All subjects were given the three treatment conditions over 3 days. The study revealed that intraocular pressure after ingesting caffeinated coffee was significantly higher than after receiving the other two treatment conditions. It was further found that increased intraocular pressure was maintained at significant levels over a 3 hour period. No significant changes were found in the pulse rate, and findings on blood pressure were inconclusive. PMID- 1741640 TI - Genital herpes: the disease experience over the first 6 months. PMID- 1741641 TI - Effects of patient-controlled analgesia on postoperative pain in adolescents. PMID- 1741642 TI - Barriers to using research findings in practice: the clinician's perspective. PMID- 1741643 TI - Using art and science to change practice. PMID- 1741644 TI - Distinguishing pancreatic carcinoma from other periampullary carcinomas by analysis of mutations in the Kirsten-ras oncogene. AB - The prevalence of Kirsten (Ki)-ras gene mutations was studied in 105 paraffin embedded tissues obtained from 40 patients with pancreatic cancer, 48 with bile duct carcinoma (19 distal, 6 middle, and 23 proximal), 16 with ampullary carcinoma and 1 with duodenal cancer, by in vitro amplification of target sequences by the polymerase chain reaction (PCR). With regard to pancreatic cancers, the authors' data confirm the very high frequency (88.6%) of Ki-ras gene mutations occurring at codon 12. Five pancreatic carcinomas did not contain the Ki-ras mutation and included rare types of histopathology. By histologic review after the examination of Ki-ras mutations through PCR, the diagnosis of four patients could be legitimately revised from other periampullary carcinoma to pancreatic carcinoma. In the ampullary carcinoma, the prevalence of mutations in Ki-ras codon 12 was 13.3%. Although there was a large difference in incidence of mutations between distal and middle or proximal bile duct carcinoma, the prevalence of mutations in bile duct carcinoma was limited to 19.6%. Unlike other approaches to diagnose periampullary carcinoma, detection of a mutation in Ki-ras codon 12 by PCR may distinguish pancreatic carcinoma from other periampullary carcinomas that have better prognoses. PMID- 1741645 TI - Pancreatic resection versus peritoneal lavage in acute necrotizing pancreatitis. A prospective randomized trial. AB - Twenty-one patients with acute fulminant alcoholic pancreatitis were randomly allocated to either pancreatic resection group (11 patients) or nonoperative peritoneal lavage group (10 patients). Only patients under 50 years were included in the study to minimize the role of other severe disease. These patients represented the most severe cases of acute pancreatitis at our Department, constituting only 2% of all patients with acute pancreatitis during this period. The diagnosis was based on clinical symptoms and on signs indicating severely impaired systemic organ functions. All patients underwent contrast-enhanced computed tomography (CT), which showed contrast enhancement below 30 Hounsfield units. In the operated cases, the diagnosis of necrotizing pancreatitis was verified histologically. All patients with conservative treatment had dark brown fluid at peritoneal puncture. There was a difference (nonsignificant) in mortality (3/11 and 1/10, respectively), complication rate, or in the need of reoperations between the groups. Nonoperative peritoneal lavage was followed with shorter treatment at the intensive care unit (16.2 versus 25.9 days, respectively). The hospital stay also was significantly shorter in the nonoperative group (44.3 versus 56.1 days). The results indicate that intensive conservative treatment is justified as an initial therapy even in the most severe cases of acute pancreatitis. PMID- 1741646 TI - Sex differences in gallstone pancreatitis. AB - From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p less than 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p less than 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p less than 0.0001). In the nonpancreatic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p less than 0.0001), and in men (p less than 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis. PMID- 1741647 TI - Causes of renal allograft loss. Progress in the 1980s, challenges for the 1990s. AB - A variety of refinements in the care of kidney transplant recipients have been instituted over the past decade. The authors studied the overall impact of these refinements on kidney allograft losses at a single institution. To do this they compared the causes and rates of graft loss for primary kidney transplants in the 1970s (January 1, 1970 to December 31, 1979; n = 1012; 657 nondiabetics, 355 diabetics; 617 living donors, 395 cadaver donors) versus the 1980s (January 1, 1980 to December 31, 1989; n = 1,384; 756 nondiabetics, 628 diabetics; 740 living donors, 644 cadaver donors). Overall patient survival improved significantly, with rates at 1, 5, and 10 years of 94%, 84%, and 68% for the 1980s, compared with 86%, 69%, and 57% for the 1970s (p less than 0.001). Actuarial graft survival also improved significantly, with rates at 1, 5, and 10 years of 86%, 71%, and 52% for the 1980s, compared with 73%, 58%, and 43% for the 1970s (p less than 0.001). This improvement occurred even though there were proportionately more cadaver donors and diabetic recipients in the 1980s. For both decades combined, 24% of the lost grafts were due to chronic rejection, 18% to cardiovascular causes of death with function, 13% to infectious causes of death with function, and 11% to acute rejection. The overall gain in graft survival rates in the 1980s was principally due to fewer cases of acute rejection and fewer infectious deaths. Improvement in graft survival due to the two leading causes--chronic rejection and cardiovascular causes of death--was relatively small, if any. These data indicate that future kidney transplantation research should emphasize prevention of chronic rejection and cardiovascular death. PMID- 1741648 TI - Elective and emergency hepatic resection. Determinants of operative mortality and morbidity. AB - To determine the reasons for improved mortality and morbidity rates after major hepatic resection, five variables were analyzed retrospectively in 300 patients operated on over a 27-year period: (1) the indication for surgery, (2) the surgical approach, (3) the urgency with which surgery was performed, (4) the nature of the surgical procedure, and (5) the experience of the surgeon. The operative mortality rate decreased from 19% between 1962 and 1979 to 9.7% between 1980 and 1988 (p less than 0.05). The operative mortality rates for patients undergoing resection for benign hepatic neoplasms was 3.4%; for metastatic tumors, 6.3%; for primary hepatic malignancies, 19%; and for trauma, 33%. Fifty seven percent of operations before 1980 were performed through a thoracoabdominal exposure as compared with 19% after 1980. Overall a thoracoabdominal exposure of the liver was associated with a 20% mortality rate as compared with 8.6% for operations with abdominal exposure of the liver (p less than 0.02). Elective operations accounted for 65% of hepatic resections before 1980, as compared with 90% after 1980, and were associated with an 8.8% mortality rate as compared with 30.7% for urgent and emergency operations (p less than 0.001). Segmental and wedge resections were associated with a 5.3% mortality rate as compared with 14.7% for major hepatic resections (p less than 0.05), but this difference did not affect overall operative mortality rates because there was no change in the proportion of major hepatic resections after 1980. Surgical experience was not a determinant of operative mortality or morbidity rates in elective operations. Although there was no reduction in the complication rate after 1980, there was a reduction in postoperative stay from 26 days before 1980 to 16 days after 1980 (p less than 0.001). A reduction in the incidence of postoperative sepsis and a change in its management was associated with improved operative mortality rates. PMID- 1741649 TI - Liver transplantation in patients with portal vein thrombosis and central portacaval shunts. AB - The authors have analyzed the impact of pre-existing portal vein pathology on the outcome of orthotopic liver transplantation. The incidence was high in patients suffering from chronic active hepatitis, hypercoagulable states, trauma or previous dissection of the porta hepatis, and splenectomy. The existence of portal vein thrombosis (23 patients) or surgical central portosystemic shunt (10 patients) was documented by preoperative Doppler sonogram or angiography (26/33), or operative findings of occluded vein (7/33). Successful thrombectomy and dismantling of portacaval shunts were achieved in most cases (24/33). Only nine patients required the placement of an interposition vein graft to the superior mesenteric vein. The intraoperative course was characterized by increased blood loss and coagulopathy, significantly higher than in patients with a patent portal vein. When compared with all liver transplants, the immediate postoperative complication rate was higher for primary nonfunction (33% versus 8%), re exploration for intraperitoneal bleeding and hematomas, and morbid infections. Rethrombosis rate of thrombectomized veins or vein graft was low (2/33). The mortality rate was 35% in the presence of portal vein thrombosis (PVT) and 30% for portacaval shuct (PCS), both significantly higher than the 12% for other orthotopic liver transplant (OLT) patients. These results are expected to improve with better patient selection, surgical experience, and anticipation of the complex postoperative course. The authors conclude that PVT or the presence of PCS are not contraindications to orthotopic liver transplantation. PMID- 1741650 TI - Experience with 100 consecutive simultaneous kidney-pancreas transplants with bladder drainage. AB - From December 1985 to December 1989, 100 consecutive simultaneous pancreas-kidney (SPK) transplants were performed at the University of Wisconsin Hospital and Clinics. Bladder drainage technique was used for all grafts. One- and three-year patient survival was 93% and 90%; kidney survival, 90% and 85%; and pancreas survival, 86% and 84%. Quadruple immunosuppressive therapy was used in all patients and consisted of either MALG or OKT3 induction, and cyclosporine, prednisone, and azathioprine maintenance therapy. OKT3 induction therapy was used in 42 patients and Minnesota antilymphocyte globule in 58 patients, with equivalent results except for more opportunistic infection with OKT3. The duodenal button technique was used in the first 17 patients with systemic anticoagulation and was associated with significantly more postoperative bleeding and infection compared with the duodenal segment technique. The most common surgical complication of the duodenal segment technique was urine leak (13%), which usually occurred from the distal duodenal segment. The most common urologic complication of bladder drainage was hematuria (13%), which was usually self limited. Within 6 months of transplantation, 84% of patients developed urinary tract infections, and 25% of patients had opportunistic infections. The surgical techniques and immunosuppressive methods used in this series are reviewed, and strategies for preventing medical and surgical complications are outlined. PMID- 1741651 TI - Depressed gut absorptive capacity early after trauma-hemorrhagic shock. Restoration with diltiazem treatment. AB - Although bacterial translocation occurs after trauma-hemorrhage, it is unknown whether gut absorptive capacity (GAC) is altered under those conditions. The aim of this study, therefore, was to determine this and also whether diltiazem (DZ) has any effect on GAC after hemorrhage. Rats (n = 12; 270 to 300 g) were lightly anesthetized with ether and a 6-cm midline laparotomy performed (i.e., trauma induced). A nasogastric tube was inserted, cannulation of a carotid and femoral artery and a jugular and the portal veins performed, and the animals allowed to recover from anesthesia. They were then bled to a mean blood pressure of 40 mm Hg within 10 minutes and maintained at this pressure by further bleeding or return of fluid (lactated Ringer's solution [LRS] ) until 40% of the shed blood volume (SBV) had been returned in the form of LRS (end of hemorrhage, EH; time from onset of hemorrhage to EH = 93.4 +/- 4.4 minutes). The rats then were resuscitated with LRS, 3 times the SBV over 45 minutes, followed by 2x over 60 minutes. One group received 400 micrograms/kg DZ, and another group received saline, with the 2x LRS. Sham animals were not hemorrhaged. Gut absorptive capacity was determined by the 1-hour D-xylose absorption test at 2 and 4 hours after EH. Results demonstrate that GAC is significantly depressed after hemorrhage and resuscitation. Administration of diltiazem restored GAC to normal levels. Thus DZ is a useful adjuvant to treatment after trauma-hemorrhagic shock, because it restores GAC to normal and allows for early enteral nutrition. PMID- 1741652 TI - The effect of glucocorticoid administration on bacterial translocation. Evidence for an acquired mucosal immunodeficient state. AB - Adherence of bacteria to intestinal epithelial cells may be the crucial initiating event for translocation and is normally prevented by both specific (secretory IgA) and nonspecific (mucus, bacterial antagonism, desquamation) mucosal defense mechanisms. The purpose of this study was to examine the effect of dexamethasone administration on mucosal immunity; specifically bacterial adherence and IgA. Twenty Fischer rats were randomly assigned to two groups of 10 animals each. Group I received 0.5 mL saline injection intraperitoneally (IP); and group II, 0.8 mg/150 g body weight dexamethasone IP per day for 2 consecutive days. The cecum mesenteric lymph nodes, and bile were aseptically collected, and bacterial adherence, bacterial translocation, and IgA concentration were determined. Results indicate that, compared with saline-treated animals, dexamethasone-treated animals had a fall in IgA (54 +/- 24 versus 232 +/- 41 micrograms/mg protein), an increase in bacterial adherence (8.2 +/- 0.5 versus 3.4 +/- 0.6 cfu (log10)/g cecum), and an increased incidence of bacterial translocation to the mesenteric lymph nodes (60% versus 0%). These data suggest that glucocorticoids may promote bacterial translocation by impairment of mucosal IgA synthesis. PMID- 1741653 TI - Surgical management of primary lymphoma of the breast. AB - Review of our surgical experience with 10 cases of "primary" lymphoma initially confined to the breast and of previous published reports indicates that radical surgery is to be avoided. Radiation therapy with limited surgery provides excellent local-regional control. The addition of systemic combination chemotherapy is warranted in the more aggressive histologic subtypes because death is generally due to subsequent disseminated disease. PMID- 1741654 TI - Chronic ACE inhibition reduces intimal hyperplasia in experimental vein grafts. AB - Intimal hyperplasia is an important factor in the pathophysiology of vein graft failure. Local renin-angiotensin systems recently have been shown to modulate the development of intimal hyperplasia in arteries after intimal injury. The effect of chronic angiotensin-converting enzyme (ACE) inhibition on the development of intimal hyperplasia in experimental vein grafts was examined in this study. Ten New Zealand White rabbits received 10 mg/kg of captopril daily in their drinking water. One week later the right carotid artery was divided and bypassed with the reversed right external jugular vein in these rabbits and in 10 matched controls. Captopril was continued for 28 days after operation, when all the grafts were harvested. Five grafts from each group were perfusion fixed, and the intimal thickness in the proximal, middle, and distal segments was determined. Rings from the remaining grafts (n = 20 in each group) were studied in vitro under isometric tension, and their responses to norepinephrine (NE), histamine (HIST), serotonin (5-HT), angiotensin I (AI), and angiotensin II (AII) was measured. The intimal thickness of the proximal, middle, and distal segments of the captopril-treated grafts were significantly less than controls, being reduced in all segments by approximately 40% (p less than 0.0001). With regard to vasoreactivity, the captopril-treated grafts were hypersensitive to 5-HT (control ED50 5.5 +/- 0.5 X 10(-7) mol/L vs. captopril-treated 1.1 +/- 0.2 X 10(-6) mol/L; p less than 0.005) although the maximal response was significantly reduced (control 1.6 +/- 0.3 g vs. captopril-treated 0.8 +/- 0.1 g; p less than 0.05). There were no differences in sensitivity between control and captopril-treated rings with respect to NE, HIST, AI, or AII. Four of the ten captopril-treated segments, however, failed to respond to AI, and the maximal active tension of the responders was significantly reduced (control 0.47 +/- 0.06 g vs. 0.20 +/- 0.05 g; p less than 0.02). These results suggest that ACE is involved in the modulation of vein graft intimal hyperplasia, and that ACE inhibitors may have therapeutic applications in patients undergoing vein bypass procedures. PMID- 1741655 TI - Can Doppler pressure measurement replace "exclusion" arteriography in the diagnosis of occult extremity arterial trauma? AB - Although highly accurate, contrast arteriography is a costly, invasive, and time consuming method to rule out occult arterial damage in injured extremities. Accordingly the authors assessed the sensitivity and specificity of Doppler derived arterial pressure measurements in trauma victims undergoing evaluation for possible extremity arterial damage. Arterial pressure index (API) was calculated (Doppler arterial pressure distal to injury/Doppler arterial pressure in uninvolved arm), but not used in clinical decision making in 100 consecutive injured limbs in 93 trauma victims. All patients then underwent contrast arteriography. Twenty limbs had an API less than 0.90 and an abnormal arteriogram, whereas 75 had both a normal API and a normal contrast study. One limb had a significant angiographic abnormality with an API greater than 0.90; two others had API less than 0.90 but normal arteriograms. Two limbs with a normal API had false-positive arteriograms. When compared with arteriography, an API less than 0.90 had a sensitivity of 87% and a specificity of 97% for arterial disruption in this series. Sensitivity and specificity rose to 95% and 97% when API was compared with clinical outcome. In the absence of obvious signs of arterial injury, API may be a reasonable substitute for screening arteriography in the traumatized extremity, particularly if close follow-up observation can be assured. PMID- 1741656 TI - Effects of stress, social support, and self-esteem on depression in children with limb deficiencies. AB - Limb deficiencies in children are the result of trauma, disease, or congenital causes. The potentially negative impact on psychologic adjustment from the chronic strain of living with limb deficiencies appears to be mediated by perceived social support (interpersonal protective factor), microstressors and daily hassles (socioenvironmental risk factor), and self-esteem (intrapersonal protective factor). These risk and protective factors were simultaneously investigated as potential predictors of depressive symptomatology in 54 children with congenital or acquired limb deficiencies. Hierarchical multiple regression analyses were used to test the main effects and the interaction effects of the predictor variables on depressive symptomatology. None of the interaction terms were statistically significant. An overall simultaneous multiple regression analysis of the main effects model predicted 72% of the variance in depressive symptomatology, with perceived classmate social support emerging as the strongest predictor variable. The findings are discussed in terms of the risk and protective effects of mediating factors on the psychologic and social adaptation of chronically ill and handicapped children. PMID- 1741657 TI - Dual-task assessment of reorganization of postural control in persons with lower limb amputation. AB - Postural control in persons with lower limb amputation was studied using a cognitive approach to motor learning. The aim of this study was to show that an important characteristic of the central reorganization process after a lower limb amputation is the gradually decreasing need of attentional resources to perform a motor task. A dual-task procedure was developed to estimate the level of automaticity of a quiet, upright standing task. The effect of a concurrent attention-demanding task (Stroop task) on the efficiency of balance control was determined using force-platform measurements at the start and the end of the rehabilitation process. In contrast with a control group, the amputation group showed interference effects on body sway caused by the concurrent task both at the start (p less than .05) and, less severe, at the end of rehabilitation (p less than .05). Improvement of balance control was significant only for the dual task condition (p less than .05). The results corroborated the hypothesis that dual tasks give information about the restoration of automaticity of postural control as an essential characteristic of the central reorganization process in persons with lower limb amputation. The role of dual-task procedures as a useful approach to skill assessment is discussed. PMID- 1741658 TI - Biomechanical gait analysis in obese men. AB - The purpose of this study was to identify and compare the kinematic components of the walking gait of obese men to those of nonobese men. Self-paced walking trials of 12 obese volunteers, ranging in age from 30 to 47 years and in obesity from 70% to 99% above ideal body weight, were recorded via cinematography. The following findings were recorded: (1) obese persons (1.09m/sec) walk significantly (p less than .001) slower than nonobese subjects (1.64m/sec); (2) obese persons take significantly (p less than .001) shorter strides (1.25m vs 1.67m) and exhibit step widths (.16m) twice those of nonobese persons (.08m); (3) mean hip abduction angles of the obese are significantly (p less than .001) different at some events of the walking cycle from the hip angles of nonobese persons; (4) mean hip and knee flexion angles are not significantly different for obese and nonobese subjects; and (5) obese individuals demonstrate a walking gait pattern with significantly greater (p less than .001) mean magnitude of ankle dorsiflexion and lesser (p less than .001) mean magnitude of ankle plantar flexion than nonobese subjects throughout the walking cycle. It is concluded that obese individuals display a walking gait that follows a normal pattern but some of the temporal and angular components of their gait are different from those of nonobese persons mainly because of the excessive adipose tissue inside their thighs. PMID- 1741659 TI - Incidence and nature of dysphagia in polio survivors. AB - Questionnaires pertaining to swallowing function were mailed to 220 members of postpolio support groups in Connecticut. Of the 109 responses, 80 individuals reported having no difficulty with swallowing, while 29 reported having either intermittent or consistent swallowing problems. Twenty-one of the 29 were seen for videofluoroscopic swallowing studies and pulmonary function testing. The swallowing studies showed that 43% of these individuals had difficulty with bolus control, 19% with delayed swallow response, and 81% with decreased pharyngeal transit. Although none of these individuals were observed to aspirate, two were judged to be at significant risk. Incidence of dysphagia within the group of polio survivors was estimated to be approximately 18%. Seventeen of the 20 postpolio subjects with dysphagia also demonstrated decreased breathing capacity. Although moderately to severely depressed values in the pulmonary function measures accompanied moderate dysphagia in certain postpolio individuals, reduced values in these same measures were also present in individuals with minimal swallowing dysfunction. Therefore, although impaired breathing may complicate swallowing dysfunction and vice versa, it does not appear that one can be predicated from the other. Management of dysphagia in postpolio individuals is discussed. PMID- 1741660 TI - Utility of the dexamethasone suppression test in the diagnosis of poststroke depression. AB - The utility of the dexamethasone suppression test (DST) in the diagnosis of depression was examined in an outpatient sample of 29 stroke patients. Results indicated that the DST's sensitivity was 15%, its specificity was 67%, and its positive predictive value was 48%. These findings suggest that the DST yields no more information than would be gained from random assignment of the diagnosis of depression. Therefore, it is not a useful measure of mood in these patients. PMID- 1741661 TI - Simulator for evaluating shoulder motion as a command source for FES grasp restoration systems. AB - A simulator has been developed to evaluate the command channels through which a quadriplegic patient controls an upper limb neural prosthesis. The simulator consists of an animated grasping task implemented on a video screen. The patient controls the motion of an animated hand on the screen by moving his or her own hand while the animated hand opens and closes under control of the tested command channel. Experiments were performed using both able-bodied and quadriplegic subjects to evaluate shoulder motion as a command-channel source. The results demonstrated that optimal combinations of shoulder command-channel parameters are subject specific, which suggests using the simulator in the prescription of upper limb neural prostheses and in training quadriplegic persons who use them. Additionally, the experimental results quantified the reduction in performance that came from using ipsilateral vs contralateral shoulder control and the enhancement in performance realized when using substitute sensory force-feedback displays. PMID- 1741662 TI - [Immunohistochemical features of nephrotoxic serum nephritis in the rat: the role of interleukin-1 in the development of heterologous and autologous stages]. AB - Late heterologous and autologous stages of serum nephritis together with glomerular cells in culture are studied biochemically, morphologically and immunohistochemically for the assessment of the role of mononuclear leucocyte mediator system. The heterologous stage of the nephrotoxic nephritis is associated with the increase of Interleukin-I and TxA2 production. Role of Interleukin-I in the autologous stage is less pronounced in spite of proliferative activity of cultured mesangial cells. The effect of suppressive factors prevails in the glomerulus. PMID- 1741663 TI - [Membranous nephropathy associated with kidney amyloidosis]. AB - 15 kidney biopsies from 13 patients with a combination of membranous nephropathy and amyloidosis were studied. Membranous nephropathy is shown to precede the development of amyloidosis which possesses all the properties of the acquired one (AA-amyloid). Transformation of membranous nephropathy into amyloidosis is due to the deficiency of the immune system characteristic of both processes. This combination is not considered as a special type of amyloidosis but as a peculiar feature of membranous nephropathy. PMID- 1741664 TI - [Role of sinusoidal cells in the morphogenesis of alcoholic liver cirrhosis]. AB - 49 liver biopsies in alcoholic liver damage (fibrosis, chronic persisting hepatitis, cirrhosis) are studied on semithin sections electron microscopically and morphometrically. Morphological varieties of hepatocytes and sinusoidal cells are revealed as well as some rules in their proportions. Domination of stellate reticulo-endotheliocytes with a high secretory and phagocyte activity correlates with high adaptive properties of hepatocytes and transformation of lipocytes into fibroblast-like cells without development of intralobular fibrosis. If nonactive variant of the stellate reticulo-endotheliocytes prevails, the number of damaged hepatocytes and fibroblast-like lipocytes increases, intralobular fibrosis becomes pronounced resulting in hepatocyte death. Role of sinusoidal cells in realization of alcoholic cirrhosis morphogenesis is discussed. PMID- 1741665 TI - [The scientific school of Medical Science academician A. I. Strukov]. PMID- 1741666 TI - [Structural-functional characteristics of phagocytes in the broncho-alveolar lavage fluid in acute focal pneumonia]. AB - The alveolar macrophages and neutrophils of the bronchoalveolar fluid from 37 patients with acute focal pneumonia were studied cytochemically. A comparison group consisted of 20 patients with primary chronic bronchitis, 11 subjects without pulmonary affections served control. Phagocytes with a high motile, oxygen-dependent bactericidal and hydrolytic activity as well as with increased level of absorptive capacity prevailed during the peak of the disease and its regression. At the phase of convalescence the number of phagocytes with a high oxygen-dependent bactericidal and hydrolytic activity decreased but their high absorptive activity was retained. PMID- 1741667 TI - [Morphogenesis of pneumonia in alcoholic intoxication]. AB - A single moderate dose of ethanol given to 120 Wistar male rats inhibits general immune defence and may facilitate the development of pneumonia. No morphological changes are found in the surfactant system in acute alcoholic intoxication. In chronic alcoholic intoxication with a pronounced withdrawal syndrome, apart from the decrease of general immune defence, lung surfactant system is damaged due to the direct ethanol effect on type II pneumocytes. These are the leading factors in the pneumonia pathogenesis characterized by a grave course and tendency to the abscess formation. PMID- 1741668 TI - [Kidney adenoma]. AB - Morphological, electron microscopic, histospectrophotometric and morphometric (mean nuclear surface and ellipticity coefficient) studies of small cortical adenomas were performed. Surgical (kidneys removed because of renal cell carcinoma and shrinkage) and autopsy (atrophic kidney) materials were used. Total 142 adenomas were found in 93 out of 592 observations. The incidence of adenomas in kidneys with renal cell carcinoma was 12%, in contracted kidneys 19.2 and 19.44% (surgical and autopsy material). Electron microscopic examination was performed in 15 adenoma cases. Comparative quantitative DNA determination was performed in sections stained by Feulgen using plug-method on the microscope spectrum analyzers in 20 cases of adenoma and 15 cases of renal cell carcinoma identical histologically to adenocarcinoma. This combined study revealed the adenomas heterogeneity. Only part of them (well differentiated with diploid DNA histograms and nuclei up to 32 mm2 may be referred to adenomas. All the others morphologically and morphometrically are close to adenocarcinomas. The type of DNA distribution and mean nuclear surface are most important for differential diagnosis between renal adenoma and carcinoma. PMID- 1741669 TI - [Morphologic manifestations of the preclinical stage of diabetic nephropathy]. AB - Kidney biopsies from 10 patients with diagnosed insulin-dependent diabetes mellitus of various duration with clinical manifestations of hyperglycemia, increased rate of glomerular filtration, presence or absence of microalbuminuria, were studied morphologically. Gradual increase of kidney alterations was observed: changes of thickness and loosening of basal membrane of glomerular capillaries, its focal homogenization, partial mesangium increase due to the increase of membranous substance and decrease of cellular component. These alterations positively correlate with immunohistochemistry of renal glomeruli. Dynamics of morphological changes does not show a direct connection with the patient age and the duration of diagnosed disease but is stipulated by the presence of one or another antigen of the class II major histocompatibility complex. PMID- 1741670 TI - [Morphogenesis of diabetic microangiopathy]. AB - Skin biopsies from 40 patients 17 to 75 years old with type I and II diabetes mellitus were studied morphologically. The formation of diabetic microangiopathy starts with the damage of endotheliocytes, vascular permeability disturbance, activation of pericytes and smooth muscle elements with subsequent thickening of basal membranes and capillary and arteriole hyalinosis, these lesions being directly related to the duration of diabetes. Diabetic microangiopathy is a manifestation of the disease and its morphology is similar in both type I and II diabetes. PMID- 1741671 TI - [Morphology of lymph nodes in secondary immunodeficiency provoked by acute diffuse peritonitis]. AB - Lymph nodes of 30 patients operated because of acute diffuse peritonitis are studied histologically and immunologically. Two types of the lymph node response are found during the reactive stage. The response of the 1st type (the beginning of peritonitis) is characterized by the activation of T- and B-immunity systems. The signs of the depression are characteristic for the 2nd type. Immunodeficiency is enhanced in toxic and terminal stages. The most informative index of the immunodeficiency degree is a decrease of the ratio T-helper/T-suppressor cytotoxic lymphocytes. There is a close correlation between the state of patients and immunomorphological changes of lymph nodes and blood. Peritonitis results in the development of vitium cordis when intoxication associated with immune disturbances strengthens both the inflammation and intoxication. PMID- 1741672 TI - [Inflammation, adaptive regeneration and dysregeneration (intercellular interaction analysis)]. AB - Inflammation, regeneration and fibrosis are inseparable components of the adaptive tissue response to damage. Systemic analysis indicates that this reaction is brought about due to the cooperative interaction of the connective tissue and blood cells (neutrophils, labrocytes, thrombocytes, macrophages, lymphocytes, fibroblasts) between each other, with intercellular matrix (collagen, fibronectin, proteoglycans) and organ parenchyma on the basis of feedback mechanisms. The role of the "cell orchestra conductor" changes at different stage of reaction; macrophage-fibroblast interaction is the most important in the cooperation between inflammation and regeneration. The breakdown of the homeostatic autoregulatory mechanisms (particularly those of intercellular and intertissue interaction) results in the disturbance of standard reactions, disintegration of inflammation and regeneration, chronicity of inflammatory reactions, incomplete regeneration, progressing sclerosis, formation of deficient granulation and fibrous tissue, tendency to the secondary destruction. The process loses the adaptive character and the notion of "dysregeneration" is introduced for its characteristics. PMID- 1741673 TI - [Congenital hypoplasia of the pancreas with lipomatosis and bone marrow dysfunction (Shwachman syndrome)]. AB - The description is given of Shwachman syndrome in a male of 17, with a long anamnesis of malabsorption syndrome, granulocytopenia, repeated bronchopneumonia, somatogenic subnanism and hypogonadism. The death resulted from acute cardiovascular insufficiency. Post-mortem examination revealed exocrine pancreas hypoplasia with lipomatosis, Wirsung duct atresia, fibrocholangiocytosis and fat hepatosis, visceral anemia, delay in the maturation of granulocytes in the bone marrow, somatogenic polyglandular endocrinopathy, metabolic myocardium necrosis, calcinosis of the small arteries wall, lymphoid tissue atrophy, focal pneumonia of the upper lobe of the left lung. PMID- 1741674 TI - [Pathogenesis of hemolytic-uremic syndrome]. AB - Current literature on the pathogenesis of the hemolytic-uremic syndrome (HUS) is analyzed. A variety of etiologic factors and mechanisms of HUS development is considered. The emphasis is laid on the endotoxinemia, damage of the renal vessel and glomerular mesangium endothelium and other mechanisms. PMID- 1741675 TI - Skeletal muscle ventricles: update after 18 months in circulation. AB - Skeletal muscle ventricles (SMVs) have been constructed from canine latissimus dorsi muscle and connected to the aorta as aortic diastolic counterpulsators. Presently one dog remains alive and well with an SMV that has been functioning continuously in circulation for 18 months, without evidence of thromboembolic complications. SMVs are able to perform cardiac-type work with an output equal to that of the left ventricle at physiologic preloads, when tested with a mock circulation device in our laboratory. SMVs have been used for right-sided cardiac assist. In acute experiments these ventricles have functioned effectively, bypassing the right side of the heart for up to 8 h. Most recently we have tested SMVs using them chronically to pump blood in the right-sided circulation, and at the time of writing they have been shown to function effectively in this configuration for up to 18 days. SMVs may be used in the future as a method of treating patients with left- or right-sided heart failure. PMID- 1741676 TI - Perspectives for pneumatic and hydraulic circulatory assist devices and their application for heart transplantation. AB - Intraventricular blood-forcing-principle-based pneumo- and hydraulic assistance circulation device test results are proposed. The system consists of a uninipple valveless dome pump, a pneumo- or hydraulic drive, and an artificial pericardium. Stand tests of these systems and medical-biologic experiments on dogs and 17 calves were performed. The duration of these experiments was up to several days. In this report, the features of surgical techniques, perfusion parameters, control principles, hemodynamic variations, complications, and other problems concerning realization of the proposed method are discussed. PMID- 1741677 TI - Biventricular bypass: alternative to univentricular bypass and total artificial heart-bridge. AB - Left ventricular and biventricular bypasses (LVBs, BVBs) were performed in 102 experiments in sheep, goats, and donkeys. Biventricular bypass was performed in the assisted circulation mode or in the paracorporeal artificial heart bridge (PCAHB) mode when the natural heart fibrillates. During implantation of artificial ventricles instead of a heart-lung bypass, counterpulsation was used. Several types of connective conduits were developed and tested in experiments. The conduits included bifurcational connective pipes that permit "intake" of blood into artificial ventricles from atria and ventricles of the natural heart simultaneously and consequently provide effective blood flow through shunts not depending on the state of the natural heart (acute cardiac weakness or asystole). Monitoring gas content (PO2, PCO2, and pH) in the myocardium of both ventricles suggested development of right ventricular failure under conditions of LVB before hemodynamic changes occurred and confirmed the preferability of BVB over other methods of assisted circulation, as it is most effective and capable of normalizing short-term cardiac disturbances in the course of the 1st 2 days. Survival time of experimental animals (2-3 days for dogs, 5-12 days for sheep, goats, and donkeys) is sufficient to overcome acute cardiac insufficiency. This suggests that BVB in the assisted circulation mode or PCAHB mode can serve as a bridge for cardiac transplantation for the time of search for the available organ. PMID- 1741678 TI - Extracorporeal mechanical pulsatile pump and its significance for myocardial function recovery and circulatory support. AB - The authors performed 12 acute (on dogs) and 12 chronic (on calves) assisted circulation experiments with the use of the total extracorporeal mechanical pump (TEMP) artificial ventricles. The functional morphological research of the myocardium suggests that in addition to the possibility of the biological heart function full replacement, the artificial ventricle also helps recover damages in both the myocardial infarction and distal zones. The critical time period up to the onset of artificial circulation is not more than 2 h, and after that myocardial changes are irreversible. PMID- 1741679 TI - Total artificial heart without valves: principles of design and implantation technique. AB - A total artificial heart (TAH) without valves is a TAH of a new design. The entry and exit are combined in one opening. The excision of the biologic ventricles is below the atrioventricular groove, while the outlet and position of the right and left ventricles are preserved. The aortic and pulmonary valves have been left intact. Bioprostheses BAKS are implanted into the mitral and tricuspidal positions. Initial experiments hold much promise: the absence of artificial valves decreases the risk of thromboemboly; the natural heart basis remains intact, which facilitates the subsequent donor heart transplantation; and the work of the new TAH is practically noiseless. PMID- 1741680 TI - Clinical indications for the use of the "Poisk-IOM" total artificial heart: the experience of 13 implantations in humans. AB - Success of total artificial heart (TAH) implantation as a temporary measure depends on three factors: proper patient selection, adequate surgical technique, and safe cardiac prostheses. From 1986 until March 1990, 237 patients with stagnant heart failure were examined. Sixty-one patients (27%) were put on a waiting list. Thirty-eight percent of them died awaiting transplantation. Thirteen TAH implantations were performed; nine patients who were not on a waiting list underwent TAH implantation by urgent indications. Four other patients underwent bridge TAH implantation after cardiac surgery. Our experience shows that the status of a patient before transplantation is a determinant factor and that it is possible to perform TAH implantation only in patients on a waiting list. PMID- 1741681 TI - Present and future of the artificial heart driving system. AB - The totally artificial heart (TAH) is now in development in two trends. First, there is the development of a bridge system for temporary support of cardiac function. The TAH with the extracorporeal pneumatic driving system Sinus-IS is more efficient and safer. Parallel with this, a portable pneumatic driving system has been developed. That can be considered a stage in the development of the second trend: a totally implantable TAH. This article reviews problems of building of the Micron energy system to be used in implantable TAH designs. PMID- 1741682 TI - The interaction of heparinized biomaterials with human serum, albumin, fibrinogen, antithrombin III, and platelets. AB - The influence of the method of heparin (HEP) immobilization on human serum albumin (HSA), fibrinogen (FG), and antithrombin III (AT-III) adsorption, platelet adhesion, and activation on the surface of polyvinylchloride, polyurethane Vitur, and a copolymer of styrene and divinylbenzene was measured. The negative correlation between the degree of irreversibility of plasma protein adsorption and the amount of adsorbed AT-III for HEP, immobilized onto the polymer surface passivated with HSA, FG, and plasma was found. The same negative correlation was observed between the amount of AT-III adsorbed on these systems and the number of adhered platelets. Schemes of the interaction of surface bound HEP with AT-III, including the influence of an irreversibly adsorbed protein layer and adhered platelets, have been proposed. The essential role of AT-III in heparinized biomaterials/platelet interaction has been shown. A new method of combined immobilization of HEP and platelet adhesion inhibitor has been elaborated on. PMID- 1741683 TI - The heterogeneity of protein/surface interactions and structural alterations of adsorbed albumin and immunoglobulin G. AB - The theoretical model is developed for the reversible and irreversible protein adsorption in kinetic regime by assuming the continuous energetical heterogeneity for protein/surface interaction and the possibility of structural alterations of adsorbed molecules. The simplest rectangular distributions of adsorption centers in energy of activation are used to explain the logarithmic kinetics of IgG and human serum albumin (HSA) adsorption on a quartz surface. To explain the Freindlich character of HSA adsorption onto a precoated surface, the exponential distributions of adsorption centers in energy of activation are used. A competitive analysis of some of the approaches allowed for the energetical heterogeneity of protein/surface interaction is made. The possibility of lateral electrostatic repulsion to form the logarithmic kinetics of HSA adsorption is checked experimentally. The influence of the temperature on HSA adsorption onto quartz is discussed also. PMID- 1741684 TI - Elastic siloxane materials for endoprosthetic applications. AB - Data are reported on properties and application in the clinical practice of elastic silicone materials for medical uses and items thereof prepared in the S.V. Lebedev All-Union Synthetic Rubber Research Institute. The effect of the implants on the neighboring tissues and on the living organism as a whole is discussed. The possibility of using the materials under consideration for endoprostheses is demonstrated. PMID- 1741685 TI - Absence of lung reactions after complement depletion during dialysis: an experimental study in pigs. AB - Sequestration of 111In-labeled neutrophils (polymorphonuclear leukocytes--PMNs) in the lungs during sham dialysis was studied dynamically using a gamma camera. Five animals were pretreated with cobra venom factor, naja naja (CVF), to achieve depletion of the complement system, mainly C5a. Seven animals were studied without pretreatment with CVF. Central hemodynamics and gas exchange were studied as well as neutrophil function using luminescence and aggregation. In the control group there was a significant sequestration of neutrophils in the lungs, which reached a maximum between 15 and 17 min after the start of hemodialysis. The peripheral neutrophil count decreased concomitantly. These changes were virtually absent in the CVF-treated group. PMN aggregation and luminescence were abolished in CVF-treated animals. Both pulmonary artery pressure and pulmonary vascular resistance increased significantly in the control group, whereas in the CVF group these parameters remained unchanged. There were no differences in blood gases, platelet count, or hematocrit between the groups. The results clearly indicate that the activation of neutrophils within minutes after the start of hemodialysis is greatly dependent on C5a activation because it can be abolished by C5a depletion. This activation is accompanied by changes in the pulmonary circulation with increases in pressure and resistance. PMID- 1741686 TI - Experimental study on the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation with an automatically driven blood pump on puppies. AB - Hemodynamics, mainly the pressure of the heart, was studied while performing veno arterial extra-corporeal membrane oxygenation (VA-ECMO) on 16 puppies between the right atrium and the right carotid artery with a unique ECMO circuit using an automatically driven blood pump. The resulting decrease in the mean pulmonary arterial pressure indicated a definite support of VA-ECMO on the volume work of the right heart. The right and left ventricular end-diastolic pressures decreased during the low flow bypass, but increased significantly with flow over 50 ml/min/kg. The results indicated biventricular pressure strain due to the increase in afterload. The left ventricular systolic pressure gradually increased despite the steady decrease in the systemic arterial systolic pressure when bypass flow exceeded 60 ml/min/kg. The findings were similar to those in peripheral circulatory insufficiency. The authors concluded that VA-ECMO flow should be kept as low as possible, in view of undesirable hemodynamic effects on both ventricles. PMID- 1741687 TI - Fluorocarbon-based oxygen carriers: new orientations. AB - Fluosol, a first, low-concentration fluorocarbon emulsion, was recently approved for oxygenating the myocardium during percutaneous transluminal coronary angioplasty. Improvements in fluorocarbon and emulsion technology have led to the development of significantly more stable, more efficient second-generation injectable O2 carriers. This progress extends the potential of fluorocarbons in medicine to new applications both in diagnostics and in therapeutics. Future objectives will aim at adjusting and optimizing the preparation's characteristics for each specific application. The emulsifier, or surfactant, which determines the external appearance of the fluorocarbon droplets, will play a key role in the mastery of emulsion properties. Extensive research efforts are therefore being directed toward the synthesis and evaluation of new families of surfactants or co surfactants specifically designed for emulsifying fluorocarbons. PMID- 1741688 TI - Biochemical changes in knee joint articular cartilage after cemented prosthetic hip hemiarthroplasty in dogs. AB - Biochemical changes in the distal femoral articular cartilage (knee joint) after cemented prosthetic replacement of the femoral head were determined. Femurs from dogs (n = 10) that had undergone cobalt-chromium prosthetic hip hemiarthroplasty (6-8 months postoperatively) were analyzed for articular cartilage lipids in the distal femur. The quantity of phosphatidylserine increased from 0.59 +/- 0.14 mg (uninvolved) to 1.52 +/- 0.23 mg (hemiarthroplasty) lipid phosphorus/100 g tissue, and the quantity of arachidonic acid in the articular cartilage increased from 0.23 +/- 0.07 mg (uninvolved) to 2.07 +/- 0.29 mg/100 g tissue (hemiarthroplasty). Likewise, hydroxyproline content was higher in the recipient femurs (77.4 +/- 1.58 micrograms/mg cartilage) versus uninvolved femurs (71.8 +/- 1.03 micrograms/mg cartilage); the activity of acid phosphatase was greater in the recipient distal femoral cartilage as compared with the uninvolved femur, 0.07 +/- 0.01 and 0.06 +/- 0.02 mol hydrolyzed per kilogram per hour, respectively, and the hexosamine content was lower in the recipient femur knee cartilage versus knee cartilage from uninvolved femurs, 54.5 +/- 1.51 and 63.1 +/ 1.37 micrograms/mg cartilage, respectively. These biochemical changes may suggest degeneration of the knee joint articular cartilage after cemented hip hemiarthroplasty. PMID- 1741689 TI - In vitro hemodynamic analysis of flexible artificial ventricles. AB - An in vitro fluid dynamic study was performed to compare the hemodynamic characteristics of a rigid and a flexible total artificial heart. The artificial ventricles were incorporated into a mock circulatory system, and pressure signals within the ventricular chamber, proximal to the inflow valve and distal to the outflow valve, were obtained. The instantaneous flow rate through the inflow and outflow valves was measured with electromagnetic flow probes. Flow visualization studies performed on the flexible ventricle suggested a vortical motion within the chamber with a smooth washout of fluid in the next pumping phase, but flow disturbances were observed near the wall of the ventricle as well as near the outflow valve. The rate of pressure increase (dP/dt) was smaller in the flexible ventricle as compared with the rigid ventricle for comparable flows and heart rates. The results of the present study indicated that the flexible ventricle with polyurethane valves, having the advantage of ease of implantation and cost savings, can be a viable alternative as a bridge to transplant. PMID- 1741690 TI - Control systems for the electric heart. AB - Methods to predict and control cardiac output (CO) accurately in total artificial heart (TAH) recipients have varied significantly in the last few decades. Early models exhibited minimal control mechanisms and involved fixed pumping parameters. Elaborate electromechanical systems that have recently evolved require intricate communication between the circulating blood volume and the electric pump to maintain blood flow to critical organs. Attempts to quantitate specific end-organ blood flow, metabolic alterations, and oxygen delivery and, finally, to link these functions to the control of the TAH have not succeeded. Current devices seek to predict the needed CO by monitoring preload, afterload, or a combination of both. No consensus has developed concerning the appropriate physiologic parameters that should be surveyed in vivo and then used to regulate the output of the TAH. PMID- 1741691 TI - Comparison of creatinine, hippuric acid, 5-hydroxyindoleacetic acid, serotonin, and pseudouridine concentrations in blood withdrawn from vein and arteriovenous fistula of uremic patients on maintenance hemodialysis. PMID- 1741692 TI - Effect of wearing complete dentures on human palatal mucosal blood flow measured by 133Xe clearance. AB - In eight edentulous subjects, who had not previously worn dentures, blood flow was measured by 133Xe clearance after intramucosal injection. Upper and lower complete dentures were then constructed for these subjects, and 133Xe clearance was measured after the dentures had been worn for 7 and 40 days. Before the insertion of dentures the mean blood flow to palatal mucosa was 18.9 +/- 7.1 ml/100 g/min. Seven and 40 days after wearing dentures the mean flows to the palatal mucosa were 10.6 +/- 4.5 and 12.6 +/- 5.3 ml/100 g/min, respectively. The difference before and after wearing dentures was statistically significant (p less than 0.05). The subjects were asked not to wear the dentures for 24 h after the third visit on the 40th day whereupon the blood flow reached almost normal levels (16.2 +/- 5.45 ml/100 g/min). The findings show that wearing dentures hinders the blood supply to the palatal mucosa, and that after resting the oral tissues, blood flow may return to normal levels. PMID- 1741693 TI - The effects of human salivary cystatins and statherin on hydroxyapatite crystallization. AB - The adsorption, at hydroxyapatite surfaces of neutral cystatin SN, acidic cystatin S and the phosphoserine-containing acidic cystatin S1 was compared to that of statherin. The effects of these adsorbed proteins on the constant composition growth kinetics of hydroxyapatite were also studied. The neutral cystatin SN had a higher adsorption maximum than the acidic cystatins S and S1. Although the affinity of cystatin for hydroxyapatite surfaces was lower than that of statherin, their influence on the growth kinetics of hydroxyapatite was considerably greater, with the acidic cystatin S1 being the most active. At a surface concentration of 7.0 x 10(-8) mol m-2 hydroxyapatite, the cystatins decreased the rate of crystal growth by 80-95% as compared to that in the absence of protein. At this concentration, statherin showed a growth inhibition of 40%. PMID- 1741694 TI - Prostaglandin E2 receptor of rat submandibular salivary glands. AB - The binding characteristics of the PGE2 receptor were investigated in membrane preparations from these glands. Specific [3H]PGE2 binding was linear as a function of the membrane protein concentration and reached steady state by 40 min of incubation at 37 degrees C under neutral pH. Scatchard analysis of the binding data produced a curvilinear plot with a Kd of 0.18 nM and Bmax of 1.02 fmol/mg protein for the high-affinity binding sites, and a Kd of 181 nM and Bmax of 5.72 pmol/mg protein for the low-affinity binding sites. A competitive displacement study indicated that the receptor was specific for prostaglandins of the E series. The study is the first to demonstrate the presence of the PGE2 receptor in rat submandibular gland and to provide its biochemical features. PMID- 1741695 TI - The permeability of cat dentine in vivo and in vitro. AB - The apparent impermeability of dentinal tubules to chemicals applied to exposed dentine in vivo was investigated. It was shown that whereas Evans' blue diffused readily into dentine in extracted teeth, it did not do so in visible amounts when it was applied in vivo. In the in vitro experiments, decreasing the pressure of the Evans' blue solution to 20 cmH2O below atmospheric apparently prevented the dye entering the tubules, while increasing the pressure of the solution to 15 cmH2O or more above atmospheric in vivo resulted in the dye penetrating the dentine in high concentrations. It is concluded that, in cat dentine in vivo, there is an outward flow of fluid through exposed dentinal tubules, and that this flow is sufficient to substantially reduce diffusion into the tubules of chemicals such as Evans' blue. PMID- 1741696 TI - Thin-layer chromatographic analyses of lipids in different layers of porcine epidermis and oral epithelium. AB - Frozen cryosections were cut parallel to the surface of porcine skin and palatal, buccal and floor-of-mouth mucosa so as to provide separate samples representing various epithelial layers. The samples were dried, extracted with chloroform:methanol, and the lipids were chromatographed on silica gel plates in various solvent systems. After charring, lipids were quantified with a scanning densitometer. Overall, greater differences in proportions and distributions of lipid components were evident between keratinized and non-keratinized epithelia than between epidermis and keratinized oral epithelium. For epidermis and palate there was an increase in neutral lipids, including ceramides, from the deeper layers to the surface; ceramides were most abundant in surface layers. In buccal epithelium there was a distinct increase in glycosylceramides toward the surface, and in both non-keratinized regions ceramides were present in only very small amounts. The results suggest that although neutral lipids may be associated with a superficial barrier layer in skin and oral mucosa, there are differences in the composition of this barrier between keratinized and non-keratinized epithelia. PMID- 1741697 TI - Changes in facial skin temperature associated with chewing efforts in man: a thermographic evaluation. AB - Eleven healthy male adults chewed hard and soft chewing-gums for 5 min. A thermographic record of the face on the chewing side was made at the beginning of, during and after the effort. Facial temperature distributions during open/close cyclic unloaded jaw movements were recorded at a later date. The dimensions of the zones whose temperatures were 1.4 degrees C or more higher than the central temperature during the experiment were determined. There was a linear increase in the dimensions of these zones after the chewing. In contrast, the cyclic jaw movements did not result in significant increases. Chewing the hard gum produced significantly higher temperature rises than did the soft in the masseter area. After the chewing effort, the temperature fell gradually, but did not return to the initial state even after 30 min. The overall decreasing pattern of the temperature distribution for chewing the soft gum was similar to that for the hard gum. The facial temperature associated with chewing efforts rose in accordance with the resistance offered by the chewing-gums. PMID- 1741698 TI - Age and gender influence on lead accumulation in root dentine of human permanent teeth. AB - 143 permanent teeth of individuals aged 14-60 yr from a non-occupationally exposed population in northern Israel were analysed for lead accumulation in a atomic absorption spectrophotometer graphite-furnace. A significant correlation was established between lead level and age. No gender correlation was found. The results suggest that any study dealing with lead accumulation in different populations has to compare groups of the same age range, ignoring the sex of the individuals. PMID- 1741699 TI - Rat sublingual salivary glands: secretory changes on parasympathetic or sympathetic nerve stimulation and a reappraisal of the adrenergic innervation of striated ducts. AB - Sublingual glands were examined by light and electron microscopy after stimulating the parasympathetic nerve (5 Hz continuously) or the sympathetic nerve (50 Hz in bursts 1 s every 10 s) and compared with contralateral, unstimulated, normal glands from each animal. Parasympathetic stimulation caused secretion of mucin from the tubulo-acini and possibly a small amount of degranulation from the demilunes but no changes were detected in the striated ducts. Sympathetic stimulation, on the other hand, had no effect on the tubulo acini or demilunes but caused a surprisingly extensive degranulation of the striated ducts plus loss of glycogen from their cells. Reassessment of the adrenergic innervation in the glands was therefore undertaken, by means of catecholamine fluorescence. This identified a regular association between adrenergic nerves and the striated ducts not only in sublingual but also in submandibular glands; features that have not previously been recognized. There was, however, only a sparse adrenergic innervation of the other parenchymal elements in the sublingual glands. PMID- 1741700 TI - Responses of calcitonin gene-related peptide-immunopositive nerve fibres in the periodontal ligament of rat molars to experimental tooth movement. AB - Nerve fibres showing CGRP-immunoreactivity were exclusively distributed around blood vessels in the periodontal ligament of normal teeth. The CGRP-positive nerves as well as the vessels were more dense during tooth movement and reached a maximum density and intensity of immunoreaction after 3 days. After that, the immunoreactive nerves gradually disappeared, and returned to the control level by the 7th day. Some of the CGRP-nerves were adjacent to bone resorptive lacunae at 3 days when active remodelling of alveolar bone was taking place. These findings suggest that the distribution of CGRP-positive nerves is dynamically changed around the blood vessels in the periodontal ligament during tooth movement, and that CGRP might affect the regulation of blood flow in the ligament. CGRP is possibly involved in the tissue remodelling, directly or indirectly, in addition to its function as a neurotransmitter. PMID- 1741701 TI - An electron microscopic study of dental plaque of the rat incisor. AB - Because rat incisors continuously erupt they provide an opportunity for the study of dental plaque at all stages of its development. The youngest plaque would be visible at the gingival margin of the tooth as it erupts, and the older plaque higher on the tooth. The ultrastructural features of these plaques were studied by transmission electron microscopy. Cocci and short rods colonized the cementum surface, forming a monolayer. The plaque had a maximum thickness of about 40 microns, with the inner third rich in fibrillar matrix and the organisms forming microcolonies perpendicular to the tooth surface. Cells were haphazardly distributed in a loose matrix on the surface of the plaque. In the area of plaque disorganization the cementum was covered by isolated groups of bacteria and the matrix had holes in it. The rat mandibular incisor may provide a unique model for study of how plaque on cementum is initially formed, matures and finally is degraded. PMID- 1741702 TI - Preliminary nuclear magnetic resonance studies on human saliva. AB - Of gustatory-stimulated human whole, parotid, submandibular and sublingual saliva only parotid saliva, a serous rather than mucous secretion, presented a relatively well-resolved proton NMR spectrum with satisfactory signal-to-noise ratio in a short time (30 min). The proton signal intensities showed significant circadian rhythms related to the circadian rhythms of protein concentrations in saliva. Age- and sex-associated differences in spectra were not observed for healthy saliva. On the other hand, marked differences in the spectra were observed for patients with suspected sialoadenitis. PMID- 1741703 TI - Electrophysiological study on a cochlear outer hair cell. AB - In order to examine the mechanoelectrical transduction of a cochlear hair cell, the electrical characteristics of the cochlear outer hair cell were studied. Both the cell dissociation technique and the patch clamp technique were used in this experiment. The membrane current gained by the voltage clamp method had a biphasic component, an initial inward current and a following outward current. After blocking the outward current by internal Cs ion and external TEA, the inward current has voltage-dependent inactivation. Also, the membrane potential change was studied by the current clamp method. PMID- 1741704 TI - Probational treatment of sudden deafness with prostacyclin: a pilot study. AB - Sudden idiopathic hearing loss has occasionally been supposed to be caused by a disturbed microcirculation in the inner ear of unknown origin. Little is known about the regulation of cochlear blood flow and the effectiveness of drugs in cochlear microcirculation. Because animal experiments gave evidence that prostacyclin (PGI2) might be one biochemical substratum of local regulators in the flow of blood in the stria vascularis, 11 patients with sudden idiopathic hearing loss were treated once for 6 h with prostacyclin (10 ng/kg body weight/min) in a first open clinical trial. In most cases prostacyclin increased hearing level (mean value: 7.4 dB/frequency/day) more than a standard therapy with pentoxifylline. The substitution of PGI2 could be another indication of a rheologic disorder--whether per se or within a larger context of inflammation like interaction--in the inner ear of patients with sudden hearing impairment. PMID- 1741705 TI - Early diagnosis of acoustic neuroma (1989) after experience of 37 cases. AB - Although the diagnosis of acoustic neuroma as classically described is generally thought to be easy, this is not always true for this so-called "ear tumor" which is localized within the internal auditory meatus. Recently, remarkable progress has been made in the diagnostic instrumentation and operative techniques used to treat acoustic neuroma, emphasizing the need for early diagnosis so that treatment can take place earlier than before. Through early diagnosis, some cases of total resection of acoustic neuroma have recently become possible, with preservation of not only facial nerve function, but preservation of auditory function as well. In the present report, we outline the early diagnosis of acoustic neuroma by summarizing 37 cases of acoustic neuroma experienced at our institution. We discuss historical presentations, and laboratory tests used in diagnosis including pure tone audiometry, speech audiometry, auditory brainstem evoked response (ABR), vestibular caloric stimulation, and computed tomography (CT) enhanced by introduction of air into the posterior fossa. Two representative cases are also presented. It should be emphasized that no clinical test is 100% sensitive or specific, and attention must be paid to chronological discrepancies in the patient's presentation and "cookbook"-type approaches to evaluation should be avoided. PMID- 1741706 TI - Hydrogen peroxide generation by eosinophils in allergic rhinitis. AB - It was the aim to study the hydrogen peroxide (H2O2) generation by eosinophils in allergic rhinitis caused by house dust which was examined in nasal secretion and peripheral blood. The concentration of H2O2 in nasal secretions was increased after nasal challenge with house dust, and subsided gradually by the increase of peroxidase activity. The population of eosinophils and H2O2 generation which was morphologically detected on the plasma membrane of eosinophils in nasal secretion, were increased with the release of eosinophil chemotactic activity after nasal challenge. Also, in peripheral blood, the number and phagocytic activity of eosinophils in extremely high density 1.102 g/ml were increased after nasal challenge. A high number of eosinophils was found in a density of 1.097 g/ml in the high IgE group, but showed less phagocytic activity than in the lower IgE group. Considering from these findings, H2O2 generation by eosinophils appeared to be an important event in tissue injury and augmentation of allergic reaction. PMID- 1741707 TI - Plasminogen activator derived from tonsillar lymphocytes of rabbits with arthus tonsillitis. AB - As an experimental model of human tonsillitis, Arthus tonsillitis of the rabbit was produced. In a previous paper, we demonstrated that an increased fibrinolytic activity in the circulating blood and increased proteolytic activity of the local tissue with Arthus tonsillitis were observed. In the present study, the mechanism of the increased proteolytic activity at the local site (tonsil with Arthus-type tonsillitis) was examined using cell cultures of lymphocytes originating from the tonsil with Arthus-type inflammation. That is, lymphocytes isolated from tonsil tissue of the rabbit were cultured in a culture medium for the short term. After culture, the used medium was collected and the presence of plasminogen activator in the culture medium and lymphocytes was investigated. It was clarified that plasminogen activator did exist in the culture medium of lymphocytes originating from the tonsil of rabbits with Arthus tonsillitis. Furthermore, addition of T cell growth factor to the culture medium of lymphocytes derived from non-treated tonsil induced the development of plasminogen activator in that culture medium. However, addition of B cell growth factor did not lead to the development of plasminogen activator activity in the culture medium. These results suggest that plasminogen activator originating from lymphocytes of the tonsil may play an important role in the increased proteolytic activity observed at the local site of Arthus tonsillitis. PMID- 1741708 TI - A double-blind study of the therapeutic efficacy of zinc gluconate on taste disorder. AB - The therapeutic efficacy of orally given zinc gluconate on taste disorder was investigated by a double-blind study in 98 patients with a chief complaint of this disease. The subjects were divided into two 49-patient groups and were orally given zinc gluconate or the placebo for up to 4 months. Improvement of taste examination and subjective symptoms was analyzed in 65 of the subjects. Although no significant difference was detected between the two groups in overall efficacy, a significant superiority of zinc gluconate to placebo was observed in patients with idiopathic and zinc-deficient taste disorder. Comparison of the improvement by Ridit analysis showed a significant therapeutic superiority of zinc gluconate. In contrast, comparison of the degree of subjective symptomatic changes. PMID- 1741709 TI - Total laryngeal stenosis in cicatricial pemphigoid. AB - Cicatricial pemphigoid in the aerodigestive system is rare, but can be life threatening. We report a case of total laryngeal stenosis. During an exacerbation, the airway of the patient was obliterated with a cicatrix and necessitated an emergency tracheostomy. Six years later when no recurrence of pemphigoid was confirmed, laryngofissure operations were performed with a satisfactory restoration of laryngeal function. Though otolaryngological treatment in the active phases is symptomatic including tracheostomy, surgical procedures should be encouraged once the disease has reached a remission. PMID- 1741710 TI - Local administration trials of interleukin-2 for head and neck cancer. AB - Recombinant interleukin-2 (rIL-2) has been administered locally in 20 patients with head and neck cancer. Two complete responses in lower lip cancer and 1 partial response in lingual cancer have been obtained. Immunohistological study reveals that tumor infiltrating lymphocytes (TILs), including activated T lymphocytes and natural killer cells, are increased after rIL-2 use. Intraarterial chemotherapy, performed subsequently to the local use of rIL-2 results in a dramatic decrease in tumor size within a short time, and a high frequency of CR cases is observed. Local use of rIL-2 is beneficial for treatment of head and neck cancers, and induction immunochemotherapy combining locally used rIL-2 and arterially infused anticancer drugs plays an important role in a multidisciplinary treatment for these cancers. PMID- 1741711 TI - Conductive hearing loss with normal tympanic membrane: fibrous change of long process of the incus. AB - This is a case of conductive hearing loss with the normal tympanic membrane due to fibrosis caused by potential inflammation of the long process of the incus. High resolution CT was a useful tool for the detection of ossicular disorder. PMID- 1741712 TI - A case report of supernumerary tooth and review of literature. AB - A boy visited an ear-nose and throat clinic for serous rhinorrhea and a tumor like mass in the nasal cavity. X-ray and computered tomographies showed a bone like mass with a slightly radiolucent center which seemed to stem from the nasal septum. A supernumerary tooth in the nasal cavity was extirpated under local anesthesia. In some reports, complications of supernumerary tooth were severe and involved areas other than the nose (cleft lip and/or palate, bilateral aniridia and ectopia lentis, familial adenomatous polyposis coli, ventricular septal defect or patent ductus arteriosus). A case had a risk of inducing severe intracranial complication. Therefore we must not overlook a supernumerary tooth. PMID- 1741713 TI - Parathyroid gland adenoma in primary hyperparathyroidism: report of two cases- chief and oxyphil cell adenoma. AB - Parathyroid adenomas are classified into two types: chief cell and oxyphil cell variants. In this report two types of parathyroid adenoma in association with hyperparathyroidism were examined. Both cases had suffered from renal calculi, and underwent operation. The laboratory tests showed high serum calcium and parathyroid hormone (PTH) levels. An exploratory surgery revealed a solitary tumor in each case. After extirpation of the parathyroid tumor these data returned to normal values. Electronmicroscopically, oxyphil cell adenoma in this report was characterized by numerous mitochondria and annulate lamellae in the cytoplasm. In some tumor cells secretory-like granules were observed. PMID- 1741714 TI - Adaptation of sleep and circadian rhythms to the Antarctic summer: a question of zeitgeber strength. AB - Adaptation of sleep and circadian rhythms was examined in three temperate zone dwellers arriving in Antarctica during summer. Rectal temperature, wrist activity, and heart rate were monitored continuously, sleep timing and quality noted on awakening, and mood and fatigue rated every 2 h while awake. Sleep was poorer in 2/3 subjects in Antarctica, where all subjects reported more difficulty rising. Sleep occurred at the same clock times in New Zealand and Antarctica, however, the rhythms of temperature, activity, and heart rate underwent a delay of about 2 h. The subject with the most Antarctic experience had the least difficulty adapting to sleeping during constant daylight. The subject with the most delayed circadian rhythms had the most difficulty. The delay in the circadian system with respect to sleep and clock time is hypothesized to be due to differences in zeitgeber strength and/or zeitgeber exposure between Antarctica and New Zealand. PMID- 1741715 TI - Tracking with a restricted field of view: performance and eye-head coordination aspects. AB - Vision through a restricted field of view (RFOV) is becoming increasingly common in aviation with the use of helmet mounted displays. Our first experiment investigated the influence of a narrow (20 degrees) binocular RFOV on performance during head-free visuo-manual tracking of a wide range (+/- 85 degrees) horizontally moving target. Second, the effects of two levels of RFOV (20 degrees, 70 degrees) on a similar tracking task presented with various eccentricities were compared to full field of view (FOV). Eye and head movement around the yaw axis were recorded and analyzed versus head-free visual pursuit alone. Tracking performance appeared moderately impaired when RFOV was set to 20 degrees, but did not improve with a 70 degrees field. Discomfort due to unusually large head movements was ruled out as a causal factor. Visuo-manual tracking apparently implies a need for head stability. RFOV degrades this basic requirement which, in turn, could explain performance impairment. Analysis of eye head coordination characteristics following FOV task conditions supports this hypothesis. PMID- 1741716 TI - Visual contrast sensitivity of U.S. Navy jet pilots. AB - Good visual contrast sensitivity (CS) is often described as a visual capability important for success as a military aviator and so has been suggested as a physical standard for personnel selection and retention. To evaluate this idea, we measured the CS of 135 U.S. Navy fighter pilots ranging in age from 24 to 44 years (mean = 30.20, S.D. = 4.06) and compared these to the CS of non-aviators. We obtained the non-aviator data from published studies of other investigators who used similar procedures with the same widely used, commercially available apparatus (Nicolet CST 2000). In addition to this comparison, we correlated the pilots' CS with their air-to-air target detection distances measured during air combat maneuver training and to their night carrier landing performance scores. The major findings were: 1) The mean CS of the aviators and the non-aviators were within +/- 1.0 S.D. of each other in most instances, and those few instances where a greater difference was found were parsimoniously explained by methodological and procedural factors; 2) sensitivities to different spatial frequencies were highly correlated among themselves, indicating much redundancy among the measurements; 3) there was no evidence of a relationship between CS and air-to-air target detection distances or night carrier landing performance. PMID- 1741717 TI - Increased plasma hypoxanthine values in humans during exposure to simulated altitude of 7,620 meters (25,000 feet). AB - In this study we have determined the effect of severe and moderate hypoxemia on plasma hypoxanthine and lactate values. Hypoxemia was induced in healthy humans in a low pressure chamber. The test subjects breathed atmospheric air at barometric pressures of 279 mm Hg and 385 mm Hg, representing a simulated altitude of about 7,620 and 5,334 m (25,000 and 17,500 ft), respectively. Exposure to 279 mm Hg represents a severe hypoxemia and all subjects exposed to this simulated altitude for 2 min showed symptoms related to hypoxia. After this exposure, plasma hypoxanthine increased by an average of 2.4 times compared to preexposure values. Exposure to 385 mm Hg represents a moderate hypoxemia and the persons tested at this simulated altitude for 45 min showed no or minor symptoms related to hypoxia and there was no change in plasma hypoxanthine values. In contrast to the unchanged plasma hypoxanthine values there was a 50% increase in plasma lactate values after 30 min exposure. We conclude that plasma hypoxanthine is a reliable marker for severe cellular hypoxia in humans and that enhanced plasma hypoxanthine levels are a rapid response to cellular hypoxia. PMID- 1741718 TI - The effect of apomorphine on operant behavior in rats under normoxic and hypoxic conditions. AB - We studied the effect of apomorphine on the performance of rats, maintained on a free-operant shock-avoidance schedule under normoxic and hypoxic (12, 10, and 8% O2) environments. In a normoxic environment, apomorphine (1, 2, 4, and 8 mg/kg, i.p.) produced stereotyped behaviors and dose-dependent increases in the rats' lever-pressing response rate. In a hypoxic environment, however, the increase of the response rate induced by apomorphine at 1 mg/kg was suppressed by the hypoxic conditions tested. At a dose of 8 mg/kg apomorphine, it was also suppressed by exposure to severe hypoxia (10 and 8% O2). These results suggest that the impairment of avoidance behavior in rats by hypoxia was not always improved by apomorphine, and that the degree of improvement depends on the combined effects of the dosage of the drug injected, the degree of hypoxia, and the type of behavior observed. PMID- 1741719 TI - Role of histamine in motion sickness in Suncus murinus. AB - The levels of histamine (HA) and tele-methylhistamine (t-MH) were determined in five brain regions of Suncus murinus (suncus) and the effects of motion stimulus or drugs influencing the turnover of these amines were studied to elucidate the role of histamine in motion sickness. Shaking the animals for 2 min increased HA contents in telencephalon and diencephalon without significantly changing the t MH levels. alpha-Fluoromethylhistidine (alpha-FMH), which is presumed to deplete the neuronal HA, tended to raise the HA levels. alpha-FMH slightly alleviated the vomiting response to motion stimulus and suppressed the HA increase in diencephalon caused by shaking. Compound 48/80, which releases HA from mast cells, did not alter the control HA levels, but effectively prevented the motion sickness and completely suppressed the motion-induced rises in HA levels. These results provide further evidence that brain HA plays an important role in the development of motion sickness. PMID- 1741720 TI - Physiological and thermal responses of males with varying body compositions during immersion in moderately cold water. AB - The effect of body composition on the thermal and metabolic responses of 24 male volunteers (20 to 35 years) was examined during 90 min of moderately cold (18, 22, or 26 degrees C) water immersion to the first thoracic vertebrae. Body composition was determined via underwater densitometry. Subjects were divided with respect to body fat (high fat (HF) = 18-22%, n = 12; Low fat (LF) = 8-12%, n = 12) and randomly assigned to one of three water temperatures. Rectal temperature (degree C) after 90 min of immersion did not differ in LF and HF at 18 degrees C (35.9 vs. 36.2), 22 degrees C (36.0 vs. 36.0), and 26 degrees C (36.0 vs. 36.3). Oxygen uptake (VO2, ml-kg-1.min-1) was greater in LF than in HF in all water temperatures. Oxygen uptake at 90 min was greater for LF than HF in 18 degrees C (11.48 vs. 9.19), 22 degrees C (9.79 vs. 4.70), and 26 degrees C (6.21 vs. 5.44). Mean skin temperature in LF and HF approached water temperature within the first 5 min. Despite the thermal strain of cold water immersion, the LF subjects were able to maintain a similar Tre compared to the HF due to a significantly greater shivering thermogenesis. PMID- 1741721 TI - Airline pilot incapacitation survey. AB - A survey, replicating one originally conducted by the International Federation of Airline Pilots' Associations (IFALPA) in 1967, was carried out to investigate the aetiology of inflight incapacitation on commercial flight decks. The questionnaire was constructed by IFALPA and distributed worldwide by its member associations. Since response to the questionnaire was voluntary, no control of the sample population was possible. The results indicate that 29% of the 4,345 respondents had been incapacitated at least once. As in 1967, gastro-intestinal symptoms accounted for the majority (58%) of incidents, other main causes being symptoms of nasal and sinus congestion ('blocked' ear and sinus pain), headaches, and faintness or general weakness. Of those who had experienced an incident of incapacitation, 48% claimed that safety was actually, or potentially, affected. However, when all respondents were asked whether they were concerned about safety in the event of incapacitation inflight (excluding take-off and landing), only 25% expressed concern. Slightly more pilots operating in three-man crews (50.5%) thought incapacitation affected the safety of the flight than those operating in two-man crews (45.3%). PMID- 1741722 TI - The adequacy of corrective lenses worn by United States Air Force aviators for annual flight medical examinations. AB - Aviators presenting for annual flight medical examinations at the 379th Strategic Hospital at Wurtsmith Air Force Base were studied to determine the prevalence of substandard visual acuity. The prevalence of the use of outdated (superseded) corrective lenses was also studied. We conducted 342 examinations on different aviators and 92 (26.9%) of these aviators were found to require corrective lenses. There were 23 (6.7%) aviators who were found to have inadequate visual acuity and 14 of these (4.1%) were found to be wearing superseded lenses. The visual screening method prescribed by the United States Air Force did not identify four of the aviators who wore superseded lenses. Three aviators were found to be wearing lenses obtained from civil sources. The study suggests that improvements could be made in U.S. Air Force visual screening and care. PMID- 1741723 TI - Brief cognitive behavior therapy in an undergraduate pilot student: a case report. AB - This is a case report of a male undergraduate pilot student referred from the aerospace medicine service because of difficulty coping with stresses associated with undergraduate pilot training (UPT). Two phases of a short-term cognitive behavioral treatment program were undertaken. The initial phase of treatment involved assisting the student to become aware of cognitive, behavioral, and physiological cues that were associated with increased levels of stress, and relaxation training. The second treatment phase involved stress inoculation strategies and coping procedures that were competency based, rather than mastery based. The latter had previously been unsuccessfully used by the student. Results indicated increases in self-reported stress management skills and in objective reports of training performance. Although generalizability of this study is limited, short-term cognitive behavioral therapy procedures are felt to be an important tool for improving the performance of UPT students, and may also reduce the probability of self-initiated elimination due to subjective stress complaints. PMID- 1741724 TI - Burn injuries from small airplane crashes. AB - Because a large amount of general aviation activity occurs in Central Florida, we reviewed our admissions for victims of small airplane crashes. We identified 13 burn victims of small aircraft accidents over a 7-year period. Of the 13, 12 survived their burn injuries, an overall survival rate of 92%. The extent of burn injury, Abbreviated Burn Severity Index (ABSI), complications, other injuries and rehabilitation potential are reviewed. Burn injury resulting from small airplane crashes is usually survivable if the patient arrives at the Burn Center alive. These burn victims generally are highly motivated individuals, are easily rehabilitated, and continue productive lives. Small airports and local hospitals should be aware of burn center availability because of the usual major extent of the burn injury. PMID- 1741725 TI - Situational awareness is more than exceptional vision. AB - Superior situational awareness, an extraordinary awareness of the total flight environment and aerial combat situation, is a significant contributor to success in aerial engagement. Review of over 1,000 published sources has led to the formulation of situational awareness as being principally in the cognitive domain. Superior awareness involves exceptional sensitivity to performance critical cues in the operational environment, an exceptional capacity to anticipate changes in system states and operational conditions, and the ability to act on those changes in a proactive mode. Three important constructs are described: 1) automatic information processing; 2) near-threshold processing; and 3) skilled memory. In combination, they constitute a pilot attribute which uniquely facilitates the full armamentarium of skills and abilities of the superior tactical pilot. PMID- 1741726 TI - A comparison of the routine medical examination of pilots in 12 air forces. AB - All air forces use routine medical examination to ensure the health of their pilots and flying safety. I compared pilot physicals in 12 air forces, and reviewed literature dealing mainly with routine medical examination of asymptomatic individuals. The discussion considers what should be done during the routine pilot examination to ensure flying safety, health and mission completion. General recommendations are given on ways to keep cost and effort within limits without failing to achieve the objective. Methods to achieve this include differentiating the intervals between examinations in different age groups and inclusion of procedures only beyond a certain age. Caution is advised when considering the inclusion of new procedures, and attention should be paid to whether such a test can be expected to produce unacceptable numbers of false positive results. PMID- 1741727 TI - The EEG in pilot selection. AB - We summarised and tabulated the literature dealing with the electroencephalogram in pilot selection published since a review in 1976. The incidence of seizure development in healthy groups with epileptiform discharges in their EEGs was found to be very low. An alternative interpretation is offered of the significance of epileptiform discharges in these groups in the context of pilot selection, and a plea is made for international standardization of procedures in this area. PMID- 1741728 TI - Sickle cell anemia trait in the military aircrew population: a report from the Military Aviation Safety Subcommittee of the Aviation Safety Committee, AsMA. AB - The question of whether sickle cell trait (SCT) is potentially dangerous to military aircrew personnel who have it and, consequently, whether such individuals should be allowed to fly in military aircraft is a very emotional issue. This article traces the evolution of how the U.S. military has dealt with the problem, and the present status of individuals with SCT in the U.S. military aviation community. Extensive studies and means for subjectively evaluating the problem were instituted by the Department of Defense in 1981, after making the decision not to restrict aircrew with the trait from aviation duties. All research projects and educational programs were abruptly stopped in 1985. Today, there are no actual restrictions on individuals with SCT for duty in the aviation and diving communities. PMID- 1741729 TI - General Armstrong's monuments. AB - During his term as surgeon general, Maj. Gen. Harry G. Armstrong was interested in the French monument commemorating the balloon flight of John Jeffries, the first American aviator, and Jean Pierre Blanchard. Maj. Gen. Armstrong proposed to visit the monument, located in a French forest, and have it renovated with appropriate multi-national ceremonies. The monument is at the landing site of the first flight across the English Channel. The authors discovered the former and current condition of the monument in Guines, France and compare that monument, of interest to Maj. Gen. Armstrong, to a new monument named for him, the newly enlarged U.S.A.F. Armstrong Laboratory. PMID- 1741730 TI - An appraisal of chemical aversion (emetic therapy) approaches to alcoholism treatment. AB - More than 35,000 alcoholics have received chemical aversion (emetic therapy) in at least 75 settings worldwide since the 1930s. This consummatory aversion (CA) treatment, which pairs ethanol ingestion with emetically induced nausea, incorporates the highly efficient variety of learning known as taste aversion (TA) conditioning. The CA literature indicates that emetic therapy should induce conditioned alcohol aversions in many alcoholics. Such aversions have been widely reported by clinicians and have been confirmed by recent psychophysiological evidence. Long standing evidence of treatment effectiveness is found in the results of private hospitals which have consistently produced 1-yr abstinence rates approximating 60%. Diminished alcohol craving is a frequently reported benefit. Few experimental evaluations have been completed, as is generally the case for all alcoholism treatments, but those which used methodologically sound temporal parameters during conditioning have supported the clinical efficacy of emetic therapy. The clear need for more definitive research notwithstanding, there are compelling indications that emetic therapy is a useful component of multimodal treatment within certain alcoholic populations. However, its availability is severely limited. Many alcoholics could probably benefit from expanded treatment availability. The time is ripe for a reevaluation of resistances to the clinical use of emetic therapy alcoholism treatment. PMID- 1741731 TI - Chemical aversion conditioning in the treatment of alcoholism: further comments. AB - The literature on consummatory aversion (CA) conditioning in rats does provide a well-developed theoretical foundation for chemical aversion conditioning. Nevertheless, differences between rats and humans in CA learning suggest caution in extrapolating from the animal laboratory to the treatment of alcoholic patients. Serious methodological problems with studies of emetic therapy with alcoholics preclude unambiguous evaluation of its effects. Emetic therapy is an intrusive and relatively costly form of treatment which has not been shown to be more effective than alternative, less costly methods. The onus is on proponents of this method to demonstrate its specific advantages over alternative treatments. PMID- 1741732 TI - Implicit and explicit memory bias for threat in post-traumatic stress disorder. AB - We investigated explicit (cued recall) and implicit (word completion) memory in Vietnam combat veterans with (n = 24) and without (n = 24) post-traumatic stress disorder (PTSD). Half of the subjects in each group encoded combat, social threat, positive, and neutral words elaboratively, whereas the others encoded these words nonelaboratively. On the cued recall test, under both encoding conditions, both groups recalled more combat words than other words. However, difference scores obtained by subtracting the mean recall for neutral words from the mean recall scores for the other words revealed that PTSD patients exhibited a relative explicit memory bias for combat words. That is, PTSD patients tended to exhibit poor memory for everything but combat words. On the word completion test, only PTSD subjects exhibited an implicit memory bias for combat words. This bias was greater for primed than for unprimed words, thereby ruling out a response bias. Such memory bias may underlie the 'reexperiencing' symptoms characteristic of PTSD (e.g. intrusive thoughts, nightmares). PMID- 1741733 TI - Biased cognitive operations in anxiety: artefact, processing priorities or attentional search? AB - It has been shown that, under certain circumstances, anxiety is associated with a processing bias favouring threatening information. To explain why this bias is apparent only on certain cognitive tasks, it has recently been proposed that the bias operates only when there is competition for processing resources. The present study sought to replicate previous evidence for the 'competition' hypothesis, while taking into account a potential confounding factor of word categorization in the stimulus materials. Anxious patients and normal controls were compared on their lexical decision times for threatening, categorized neutral and uncategorized neutral words that were presented either alone or accompanied by irrelevant nonword stimuli (i.e. absence vs presence of competition). The results were only partially consistent with previous findings and highlighted the importance of considering separately the effects of word valence and word categorization. When the latter was taken into account, the results indicated that an anxiety-related bias was only evident when there was competition for processing resources and when the information was presented outside the focus of Ss' attention. A modified version of the competition hypothesis was proposed in the light of these results and previous research into attentional biases in anxiety. PMID- 1741734 TI - Evaluation of thermal biofeedback treatment of hypertension using 24-hr ambulatory blood pressure monitoring. AB - Ten male hypertensives, whose BPs were controlled on a combination of sympatholytic and diuretic medications, were given 16 sessions of thermal biofeedback prior to attempting withdrawal from the sympatholytic drug. Results were evaluated using 24-hr ambulatory BP monitoring (ABPM) as well as clinic and home BPs, both in multi-baseline-across-subject designs and as a single group. Results showed significant treatment effects on 24-hr ABPM data, both at the individual level (SBPs only) and in the aggregate analyses (SBP and DBP). BPs assessed in the clinic by random zero sphygmomanometer and patient-assessed home BPs were also reduced. PMID- 1741735 TI - Prevalence of DSM-III-R disorders among nonclinical compulsive checkers and noncheckers in a college student sample. AB - The prevalence of lifetime DSM-III-R disorders was assessed in a sample of 100 college students who were classified as compulsive checkers (n = 50) or noncheckers (n = 50) on the basis of their responses to the Checking subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI). DSM-III-R disorders were assessed on the basis of responses to the Diagnostic Interview Schedule, Version III Revised (DIS-III-R), administered by trained, lay interviewers, blind to Ss' checking status. Checkers, compared to noncheckers, were significantly more likely to meet lifetime diagnostic criteria for Major Depressive Episode, Drug Abuse/Dependence, and Social Phobia. Analysis of a subsample (n = 74) selected on the basis of the consistency of responses to the MOCI across two administrations replicated the above effects, with two exceptions: (1) checkers were more likely to meet criteria for Obsessive Compulsive Disorder than were noncheckers, and (2) for males, but not females, Simple Phobia was more prevalent among checkers than among noncheckers. These findings extend our previous work by demonstrating that 'nonclinical' checking behavior is associated with a broad range of psychological syndromes and may, in fact, be more strongly associated with other disorders than it is with Obsessive Compulsive Disorder in a nonclinical sample. PMID- 1741736 TI - Assertiveness, social support, and psychological adjustment following spinal cord injury. AB - Tested predictions that assertiveness and social support would be significantly predictive of psychological adjustment. Furthermore, it was anticipated that assertiveness and certain types of social relationships would differentially interact to predict adjustment, since positive and negative effects of both variables have been noted in prior research. Trained raters interviewed 156 persons receiving either in-patient or out-patient care for cord injuries and administered measures of assertiveness, social support, depression and psychosocial impairment. Persons who reported a keen sense of responsibility for the welfare of another reported more depression and impairment. Persons reporting higher levels of support facilitating social integration and reassuring personal worth were less depressed. Several significant interactions between assertiveness and different social support relationships revealed beneficial and deleterious effects on depressive behavior and impairment secondary to the disability. Results are discussed as they advance theoretical understanding of the effects of assertiveness and social support. Implications for discriminate cue learning in assertion training for persons with physical disability are proposed. PMID- 1741737 TI - What is the revised Fear Survey Schedule for Children measuring? AB - This study was designed to investigate parameters of children's fear in terms of frequency of fearful thoughts and avoidance behaviour. It is suggested that current measures such as the Fear Survey Schedule for Children--Revised (FSSC-R) do not assess fearful behaviour in the sense of the occurrence of fearful responding in daily life, but rather reflect a negative affective response to the thought of occurrence of specific events. A modified version of the FSSC-R examined the frequency of fearful thoughts/feelings and avoidance activities amongst 376 children aged 7-12 yr. Contrary to predictions, it was found that children reported high levels of fearful thoughts and avoidance behaviour to those items identified as the greatest fears on the FSSC-R, namely fears of injury, illness, death and danger. These events were typically of low probability (e.g. earthquakes) and the question was raised as to what children are responding to when they are asked to rate their fearful responses. The same pattern of results was reflected in older compared to younger children. It is suggested that even when children are asked to rate frequency of fearful thoughts or avoidance behaviour, they tend to respond to fear questionnaire items according to their affective response to the image or thought of the stimulus situation rather than their actual fear responses. Both the FSSC-R and the modified version were found to discriminate between teacher nominated high and low fearful children and to correlate significantly with a self report measure of anxiety. PMID- 1741738 TI - Cognitive-behaviour therapy in the treatment of chronic, occupational pain of the upper limbs: a 2 yr follow-up. AB - Nineteen Ss who experienced chronic, occupational pain of the upper limbs and who had previously completed a programme of either individual or group cognitive behaviour therapy were followed up 2 yr later. Significant improvements on measures of depression, anxiety, coping strategies and interference in daily living were found following treatment. Such improvements were not evident for the waiting list control Ss and no difference was found between group vs individual applications of therapy. A 2 yr follow-up, significant improvements from pre treatment levels were evident for depression, coping strategies, significant other report of disability, self monitored pain and distress caused by pain. While there was generally little evidence of relapse, a significant decline from post-treatment levels was found for the individual therapy condition compared to the group therapy condition on measures of self monitored pain and interference caused by pain. Since post-treatment levels tended to be somewhat superior for the individual therapy condition, the overall finding at 2 yr follow-up was of minimal difference in outcome for group vs individual forms of cognitive behaviour therapy. Despite improvements from pre-treatment levels, the vast majority of Ss still reported significant and distressing levels of pain at 2 yr follow-up. PMID- 1741739 TI - Probing of the expression of the low-density lipoprotein receptor in vivo using an anti-receptor monoclonal antibody. AB - MAC188 is a rat anti-[low-density lipoprotein (LDL) receptor] monoclonal antibody (McAb) which binds to the cell surface receptor with high affinity at physiological temperatures, even in the presence of high concentrations of the natural ligand, LDL. Binding of McAb MAC188 at 37 degrees C is followed by internalization and intracellular sequestering of the receptor, which results in the transient disappearance of the receptor from the cell surface. The high binding affinity and epitope specificity of McAb MAC188 suggested that this antibody could be used to quantify receptor expression in vivo. Mixtures of radiolabelled anti-receptor antibody and a control McAb (MAC221) were injected intravenously into rabbits, and the clearance from serum and uptake into tissues was determined. A fraction of the anti-receptor McAb was cleared rapidly from the circulation by a high-affinity and saturable (receptor-dependent) process. Receptor-dependent uptake of the anti-receptor McAb was measurable in liver, adrenal glands, kidneys, spleen, kidney, thoracic aorta and heart. It was highest in liver and adrenal glands and correlated well with the level of receptor protein and the rate of LDL transport in individual tissues. Anti-receptor McAbs such as MAC188, with suitable domain specificity and binding affinity at physiological temperatures, have important advantages over the natural ligand as tracers for the receptor in vivo, and may find widespread applications in studies of the receptor status (activity) in animals and man. PMID- 1741741 TI - Rates of reactions catalysed by a dimeric enzyme. Effects of the reaction scheme and the kinetic parameters on co-operativity. AB - For the reaction S in equilibrium P catalysed by a dimeric enzyme, the reaction schemes are considered on the basis of the KNF model. For each of the ten possible schemes, the rate equation is derived on the basis of the combined steady-state and rapid-equilibrium assumptions. The curves of the plots of initial velocity v versus the substrate concentration [S] and the Hill coefficients h calculated from the rate equations depend strongly on the reaction scheme and the parameter X1. This parameter is defined by log (KS2/KS1) and is a measure of the relative affinities of the first and second protomers for the substrate. When X1 less than 0, v-[S] curves for some schemes exhibit negative co operativity (h less than 1.0) and v-[S] curves for other schemes are similar to that of the Michaelis-Menten scheme, indicating that, even if there is interaction between the distinct protomers, sigmoidal rate behaviour is not necessarily observed. When X1 greater than 0, all the reaction schemes except one, which shows substrate-inhibition kinetic behaviour, exhibit sigmoidal kinetic behaviour (h greater than 1.0), and at the limit of X1 much greater than 0 the Hill coefficients attain the maximum possible value of 2.0. Furthermore, we have found that, even if X1 = 0, the v-[S] curve for almost all the schemes considered in the present work does not necessarily agree with that for the Michaelis-Menten scheme. This means that the deviation of the v-[S] curve from a hyperbola can be observed even if there is no interaction between the distinct protomers. PMID- 1741740 TI - Modulation of complement gene expression by glucocorticoids. AB - The addition of dexamethasone, prednisolone or cortisol (in order of efficacy) to human monocytes in culture produced dose-related increases in the synthesis rates of the complement components C1 inhibitor (C1-inh), factor B (B) and C2. In contrast, concentrations of C3 and lysozyme in the culture supernatants were decreased. Indomethacin stimulated synthesis of C1-inh, C2 and B, but had little effect on synthesis of C3 or lysozyme. The simultaneous addition of cycloheximide (2.5 micrograms/ml) abrogated the effects of dexamethasone on synthesis of C2, B and C1-inh, but the effect of indomethacin on the synthesis of these components was unchanged. These data suggest that protein synthesis is required for the effects of glucocorticoids on the synthesis of C2, B and C1-inh to occur. Dexamethasone and indomethacin increased the abundances of C1-inh mRNA, B mRNA and C2 mRNA in parallel with changes in the synthesis rates of these proteins. The changes in mRNA abundance were not transcriptional, but were shown to be due to increased mRNA stability. In contrast, dexamethasone decreased the expression of C3 and lysozyme by decreasing the rate of transcription of these genes. Indomethacin had no effect on transcription of the C3 and lysozyme genes. The half-lives of C3 mRNA, lysozyme mRNA and actin mRNA were not altered by dexamethasone or indomethacin. It is concluded that the effects of glucocorticoids on monocyte synthesis of C2, B and C1-inh are due to increased mRNA stability and may be related to inhibition of prostaglandin synthesis, as these effects are similar to those produced by indomethacin. The effects of dexamethasone on the synthesis of C3 and lysozyme differ from those on C2, B and C1-inh as they depend upon a decrease in gene transcription, which is not affected by indomethacin. PMID- 1741742 TI - Structural studies on the [Bu(t)-Cys18](19-37)-fragment of human beta-calcitonin gene-related peptide. AB - High-field n.m.r. studies were undertaken upon a peptide fragment of the C terminal region of human beta-calcitonin-gene-related peptide (beta-hCGRP). Studies on the antigenic [Bu(t)-Cys18]beta-hCGRP-(19-37)-fragment revealed that several elements of secondary structure were present when the peptide was dissolved in [2H6]dimethyl sulphoxide. In particular an unspecified turn in the region of Ser19-Gly20 and a type I beta-turn in the region of Asn31-Val32-Gly33 were identified. Through-space connections between the terminal Phe37 amide group and the beta-protons of Thr50 suggest that the peptide may be folded into a loop type conformation. These structural elements appear to overlap with the epitopes of a number of monoclonal antibodies and provide a molecular basis for understanding the role of the terminal Phe37 amide residue in the immune recognition of beta-hCGRP. PMID- 1741743 TI - Transforming-growth-factor-beta activation elements in the distal promoter regions of the rat alpha 1 type I collagen gene. AB - We have located a cis-acting element (alpha 1-TAE) within the promoter sequences of the rat collagen alpha 1(I) gene (COL1A1) 1600 bases upstream of the transcription start site which mediates transcriptional activation by transforming growth factor beta (TGF-beta). The functional significance of this region was established by (1) deletion analysis of the alpha 1(I) promoter cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and (2) by co-transfection of promoter constructs with double-stranded oligonucleotides. DNA mobility-shift assays with radiolabelled alpha 1-TAE demonstrated increased nuclear binding activity after TGF-beta stimulation. Oligonucleotides encoding the alpha 1-TAE, additional upstream regions within the alpha 1(I) promoter, as well as consensus nuclear-factor-1 (NF-1) sequences, competed with the alpha 1 TAE sequence. The two collagen type I genes are stimulated by TGF-beta through different regions of their promoters. PMID- 1741744 TI - Characterization of the interaction between p100, a novel G-protein-related protein, and rat liver endosomes. AB - p100 is a recently identified 100 kDa protein which shares a putative receptor binding sequence with the signal transducing G-proteins Gt and Gi. In liver, p100 immunoreactivity is distributed between the cytosolic and the microsomal fractions [Traub, Evans & Sagi-Eisenberg (1990) Biochem. J. 272, 453-458; Udrisar & Rodbell (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 6321-6325]. More specifically, we have localized the membrane-associated form of p100 to an endosomal subfraction of rat liver microsomes. In this study we have investigated the nature of the interaction between p100 and microsomal membranes. p100 was located on the cytoplasmic surface of the microsomal vesicles, and could be released by treatment with 0.5 M-NaCl or 0.5 M-Tris/HCl, pH 7.0. However, p100 was not released by non-ionic detergents, such as Triton X-100. Binding of p100 to the membrane was reversible, as both membrane-released and cytosolic p100 could re bind stripped (Tris-washed) microsomes. Soluble p100 could not, however, bind to untreated microsomes. Binding to stripped microsomes approached saturation and was inhibited by up to 60% by either heat treatment or mild trypsin treatment of the vesicles. This implies that the interaction between p100 and the microsomal vesicles involves the direct binding of p100 to vesicular proteins. This binding was regulated by both adenine and guanine nucleotides. As p100 contains a region similar to the C-terminal decapeptide of alpha i, (the alpha-subunit of Gi) and has a localization that is restricted to an endosomal subfraction, we propose that cytosolic p100 may bind to cytoplasmically exposed domains of internalized receptors. Thus, like the adaptins, p100 may be involved in the process of sorting and receptor trafficking through the endosomal compartment of the cells. PMID- 1741745 TI - Postnatal changes in sialylation of glycoproteins in rat liver. AB - Glycoproteins containing N-linked oligosaccharides were prepared from plasma and liver microsomes of rats aged 0-5 weeks, and galactose and sialic acid content were determined. The sialic acid/galactose ratios in plasma membrane N-glycans remained at about 1 throughout the postnatal period, suggesting that most of the galactose residues are sialylated. In the same way, it was suggested that most of the galactose residues of microsomal N-glycans were sialylated at 0, 4 and 5 weeks of age, but that the degree of sialylation was lower at the other ages, with a minimum at 2 weeks. When the activities of sialyltransferase and galactosyltransferase in liver Golgi membranes were determined, age-dependent changes were found, not only in the specific activities of the enzymes, but also in the Golgi membrane content per g of liver. The activity of galactosyltransferase per g of liver increased immediately after birth, whereas that of sialyltransferase remained at a low level for 2 weeks and then increased to a constant level at 4 weeks. It is probable that this delayed increase in the activity of sialyltransferase results in the decreased sialylation of microsomal N-glycans at 1, 2 and 3 weeks. Sialyltransferase was solubilized from the liver microsomes of rats aged 2, 3 and 4 weeks and characterized. Phosphocellulose column chromatography separated the activity into two subfractions, designated transferase I and transferase II in the order of elution. The increase in total sialyltransferase activity during this period was caused mainly by an increase in transferase I. Rechromatography of each transferase from 3-week-old rats after neuraminidase treatment showed that transferase I but not transferase II contained sialic acid residue(s) and that desialylated transferase I was eluted in a similar way as transferase II. Although the apparent Km value for CMP-N acetylneuraminic acid and the heat stability of transferase I were different from those of transferase II, the difference was abolished by treating transferase I with neuraminidase, suggesting that transferase II may be a desialylated form of transferase I. These changes in the sialylation of membrane glycoproteins, including sialyltransferase, may be related to the control of liver growth during postnatal development. PMID- 1741746 TI - T-kininogenase activity of the rat submandibular gland is predominantly due to the kallikrein-like serine protease antigen gamma. AB - T-kininogen, the major kininogen in rat plasma, releases Ile-Ser-bradykinin (T kinin) when incubated with trypsin, but is not a substrate for tissue kallikrein. Enzymes able to release T-kinins from T-kininogen have been found in the rat submandibular gland, but precise identification of these enzymes and their possible relationship to kallikrein-like enzymes has not been established. We studied T-kininogenase activity in fractionated submandibular gland homogenate. The main T-kininogen catalytic enzyme was purified and characterized, and found to be identical to antigen gamma, a kallikrein-like enzyme which we have previously characterized. Of other identified kallikrein-like enzymes only tonin showed weak T-kininogenase activity, which was about 0.25% of that of antigen gamma. No other T-kininogen catalytic enzymes were observed. Antigen gamma released a kinin which was identified as T-kinin by reverse-phase h.p.l.c. The T kininogenase activity of antigen gamma had a Km of 29 +/- 4 microM and a kcat/Km of 140 M-1.s-1, and was comparable with its high and low molecular mass kininogenase activity (7.4 and 10 micrograms of kinin/h per mg respectively). In contrast, tissue kallikrein released 0.2 and 42,200 micrograms of kinin/h per mg respectively. Thus antigen gamma is a weak kininogenase. The isoelectric point of antigen gamma, but not its molecular mass, differed from that of other kallikrein like enzymes. Isoelectrofocusing in flat-bed gels combined with immunostaining was therefore a convenient method for identification. The kallikrein-like nature of antigen gamma was demonstrated by its immunological similarity to tissue kallikrein and tonin and by 91% and 87% amino acid sequence similarity with tonin and kallikrein respectively (67 amino acids sequenced). Complete identity was also not observed with other sequenced kallikrein genes, mRNAs or proteins. PMID- 1741747 TI - Mechanisms of spermine toxicity in baby-hamster kidney (BHK) cells. The role of amine oxidases and oxidative stress. AB - Spermine was toxic to BHK-21/C13 cells in the absence of any extracellular metabolism of the amine. Inhibition of copper-containing amine oxidases with aminoguanidine partially prevented the response, whereas inhibition of polyamine oxidase with MDL-72,527 exacerbated the effect. Oxidation by an intracellular copper-containing amine oxidase may be involved in the toxicity of spermine, whereas the polyamine-interconversion pathway appears to play a cytoprotective role. There was no evidence for spermine imposing a state of oxidative stress within the cells. Inhibition of catalase and glutathione reductase did not alter the cytotoxicity of spermine, and there was no excretion of oxidized glutathione into the extracellular medium. The results suggest that spermine itself can exert a toxic effect directly on the cells. PMID- 1741748 TI - Killing of cells by perforin. Resistance to killing is not due to diminished binding of perforin to the cell membrane. AB - Different cell types vary widely in their susceptibility to killing by the pore forming cytolytic molecule perforin. In particular, the cells responsible for synthesis of perforin, i.e. cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, are very resistant to cytolysis by this molecule. It has previously been suggested that resistance is due, at least in part, to diminished binding of perforin to these cells. The purpose of the present study was to compare binding of perforin to sensitive and resistant cell types. To this end, perforin was biosynthetically labelled prior to purification. The purified labelled protein was then utilized to obtain a direct measure of the amount of perforin bound to cells during attack. Resistant cells (CTL, neutrophils) bound at least as much perforin as did sensitive cells (K562, HL60 etc.), indicating that resistance to perforin involves mechanisms operating after binding of the lytic molecule. PMID- 1741749 TI - Degradation of glucagon in isolated liver endosomes. ATP-dependence and partial characterization of degradation products. AB - Endosomes have recently been identified as one major site of glucagon degradation in intact rat liver. In this study, a cell-free system has been used to assess the role of ATP-dependent acidification in endosomal glucagon degradation and identify the glucagon products generated. Percoll gradient fractionation of Golgi endosomal fractions prepared 10-30 min after injection of [125I]iodoglucagon showed a time-dependent shift of the radioactivity towards high densities. Regardless of time, the radioactivity was less precipitable by trichloroacetic acid (Cl3Ac) at high densities than at low densities. Chloroquine treatment slightly increased the density shift of the radioactivity and decreased its Cl3Ac precipitability throughout the gradient. Incubation of endosomal fractions containing [125I]iodoglucagon in 0.15 M-KCl at 30 degrees C resulted in a time- and pH-dependent generation of Cl3Ac-soluble radioactivity, with a maximum at pH 4 (t1/2, 7 min). At pH 5, 1,10-phenanthroline, bacitracin and p chloromercuribenzoic acid partially inhibited [125I]iodoglucagon degradation. At pH 6-7, ATP stimulated [125I]iodoglucagon degradation by 5-10-fold and caused endosomal acidification as judged from Acridine Orange uptake. The effects of ATP were inhibited by chloroquine, monensin, N-ethylmaleimide and dansylcadaverine. Poly(ethylene glycol) (PEG) precipitation of the radioactivity associated with endosomes showed that lowering the pH below 5.5 caused dissociation of the glucagon-receptor complex, and that, regardless of incubation conditions, all degraded [125I]iodoglucagon diffused extraluminally. On h.p.l.c., at least three products less hydrophobic than [125I]iodoglucagon were identified in incubation mixtures along with monoiodotyrosine. Radiosequence analysis of the products revealed one major cleavage located C-terminally to Tyr-13 and two minor cleavages affecting Thr-5-Phe-6 and Phe-6-Thr-7 bonds. It is concluded that glucagon degradation in liver endosomes is functionally linked to ATP-dependent endosomal acidification and involves several cleavages in the glucagon sequence. PMID- 1741750 TI - Molecular interaction of the proteasome (multicatalytic proteinase). Evidence that the proteasome is not a constituent of the '26 S' multienzyme complex. AB - On the basis of recent reports that suggested that proteasomes, via an ATP dependent process, become integral components of a '26 S' complex possessing 3 carboxypropionyl-Leu-Leu-Val-Tyr 4-methylcoumarin-7-ylamide-hydrolysing activity, we have investigated the molecular interaction of proteasomes in ATP-stabilized fraction II (proteins absorbed on DEAE-matrix and eluted with 0.5 M-KCl) of rabbit reticulocytes and mouse liver. Analysis of the various extracts by (NH4)2SO4 fractionation, velocity-gradient centrifugation, non-denaturing PAGE and SDS/PAGE and immunoblotting with proteasome-specific antisera failed to identify the proteasome as part of a higher-molecular-mass '26 S' multienzyme complex. In all instances proteasomes are identified in their 'free' 650 kDa '20 S' form. In addition to the proteasome and independent of the presence of MgATP, we isolated a high-molecular-mass proteinase whose electrophoretic migration behaviour and sedimentation rate correspond to that of the previously described '26 S' proteinase. This '26 S' proteinase possesses a strong 3-carboxypropionyl Leu-Leu-Val-Tyr 4-methylcoumarin-7-ylamide-hydrolysing activity and is composed of several non-identical polypeptides in the molecular-mass range 20-150 kDa. Despite its similarity to proteasomal enzyme activity, protein analysis and immunoblotting experiments demonstrate that neither the intact proteasome nor subunits thereof are components of the '26 S' proteinase complex. PMID- 1741751 TI - Rapid and selective modification of phosphoserine residues catalysed by Ba2+ ions for their detection during peptide microsequencing. AB - The beta-elimination of phosphoserine residues by dilute alkali is catalysed by the presence of group II metal ions. The use of 0.1 M-Ba (OH)2 catalysed the rate of beta-elimination of phosphoserine by more than two orders of magnitude compared with the use of NaOH at the same OH-ion concentration. Serine and threonine residues are unaffected by this treatment. Free thiol groups and disulphide bonds are labile to these conditions, but carboxymethylcysteine is stable. The rate of beta-elimination of O-glycosidically linked moieties is not catalysed under these conditions, and the rate of reaction is thus two orders of magnitude slower than for phosphoserine. This specific catalysis was readily exploited in the rapid and selective modification of phosphoserine residues under mildly alkaline conditions with the nucleophile methylamine via the alpha beta desaturated dehydroalanine intermediate to yield the beta-methylaminoalanine residue. This modified residue could be easily detected on sequence analysis and in amino acid compositions. PMID- 1741752 TI - Kinetics of the interaction of chymotrypsin with eglin c. AB - The kinetics of binding of recombinant eglin c to bovine pancreatic chymotrypsin was studied by conventional and stopped-flow techniques. With nanomolar enzyme and inhibitor concentrations, the inhibition was fast and pseudo-irreversible (k(assoc.) = 4 x 10(6) m-1.s-1 at 7.4 and 25 degrees C). Reaction of the enzyme inhibitor complex with alpha 1-proteinase inhibitor, an irreversible chymotrypsin ligand, resulted in a slow release of free eglin c, which was monitored by electrophoresis (k(dissoc.) approximately 1.6 x 10(-6) s-1, t1/2 approximately 5 days). The proflavin displacement method and a stopped-flow apparatus were used to monitor the association of chymotrypsin with eglin c under a wide range of inhibitor concentration and under pseudo-first-order conditions. At pH 7.4 and 25 degrees C or 5 degrees C, or at pH 5.0 and 25 degrees C, the pseudo-first-order rate constant of proflavin displacement increased linearly with eglin c up to the highest concentration tested, suggesting a one-step bimolecular association reaction: E + I in equilibrium with EI. However, kassoc. is much lower than the rate constant for a bimolecular reaction and its activation energy (66 kJ.mol-1 at pH 7.4 and 78 kJ.mol-1 at pH 5.0) is far too high for a diffusion-controlled step. The enzyme-inhibitor association may therefore occur via a loose pre equilibrium complex EI* (Ki* much greater than 5 x 10(-4) M) that rapidly isomerizes (k2 much greater than 2 x 10(3) s-1) into an extremely stable final complex (Ki approximately 4 x 10(-13) M). Unlike other proteinase-inhibitor systems, the chymotrypsin-eglin association is virtually pH-independent. PMID- 1741753 TI - Progesterone and oestradiol increase cytosolic Ca2+ in single rat hepatocytes. AB - Progesterone (300-400 microM) and oestradiol (25-200 microM) induce a prompt rise in the cytosolic free Ca2+ concentration (free Ca) in single rat hepatocytes, but testosterone, cortisol and dexamethasone do not. These increases are dependent on the presence of extracellular Ca2+. Both progesterone and oestradiol block phenylephrine-induced free Ca oscillations. These data suggest a certain specificity of the response of free Ca to steroids and may explain some of the non-genomic effects of these steroids on hepatocytes. PMID- 1741754 TI - pH-dependency of basic ligand binding to alpha 1-acid glycoprotein (orosomucoid). AB - The binding interactions of a series of basic ligands with alpha 1-acid glycoprotein (AAG) were examined as a function of pH. The binding to AAG increased with increasing pH, and the binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of neutral (non-protonated) and protonated forms of ligands. It was shown that ligands in the neutral form have a markedly higher affinity for AAG than the protonated forms, resulting in a concomitant decrease in the pKa of bound ligands. The u.v.-visible difference spectra generated upon binding of a representative ligand to AAG also showed that there was a contribution to the binding arising from the deprotonation of the ligand. It is suggested that all tested ligands bind similarly to AAG and that hydrophobic interactions dominate high-affinity binding to AAG. PMID- 1741755 TI - Identification of a novel serum amyloid A protein in BALB/c mice. AB - Four serum amyloid A protein (SAA) genes and two SAA gene products, SAA1 and SAA2, were identified in BALB/c mice. Using analytical isoelectric focusing we have identified a quantitatively significant new member of the SAA family and designated it 'SAA5'. This protein has characteristics never before described for any SAA molecule. In the highly conserved region between amino acids 33 and 44, identical in all SAAs from all species examined, SAA5 had four amino acid substitutions. In addition, the induction of SAA5 by lipopolysaccharide had different kinetics from that of the other mouse SAAs. Our data suggest that the mouse SAA gene family is more complex in composition and regulation than previously surmised. PMID- 1741756 TI - Comparison of the domain-level organization of starch hydrolases and related enzymes. AB - Structure-prediction and hydrophobic-cluster analysis of several starch hydrolases and related enzymes indicated the organization of eleven domain types. Most enzymes possess a catalytic (beta/alpha)8-barrel and a smaller C-terminal domain as seen in crystal structures of alpha-amylase and cyclodextrin glucanotransferase. Some also have a starch-granule-binding domain. Enzymes breaking or forming endo-alpha-1,6 linkages contain domains N-terminal to the (beta/alpha)8-barrel. PMID- 1741757 TI - Hydrolysis of transforming growth factor-alpha by cell-surface peptidases in vitro. AB - Human transforming growth factor-alpha (h-TGF alpha), a 50-amino acid residue peptide, was incubated with some purified cell-surface peptidases and with renal microvillar membranes prepared from pig and rat. Hydrolysis was monitored by h.p.l.c. and activity by a biological assay. Prolonged incubation with relatively large amounts of endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A (angiotensin-converting enzyme) caused no observable hydrolysis and no detectable loss of biological activity. Incubation with pig renal microvilli also failed to degrade the peptide. In contrast, rat renal microvilli readily degraded h-TGF alpha, as did endopeptidase-2, which is located in rat renal and intestinal brush borders, but is absent from pig kidneys. This enzyme degraded about 30 nmol of h TGF alpha/h per mg of protein. The physiological significance of these results is discussed. PMID- 1741758 TI - Preferential release of catecholamine from permeabilized PC12 cells by alpha- and beta-type protein kinase C subspecies. AB - Protein kinase C (PKC) is now recognized as comprising two groups of closely related subspecies. The PKC gamma enzyme is apparently present only in central nervous tissues, and hence was expected to participate in neurotransmitter release. We have utilized a 'depletion-insertion' method to identify the PKCs participating in the exocytotic response. PC12 cells were 'down-regulated' by prior treatment (24 h) with phorbol 12-myristate 13-acetate (PMA; 1 microM), which nearly abolished endogenous PKC activity. Down-regulated PC12 cells were loaded with [3H]dopamine, permeabilized with digitonin, and recombinant or purified PKCs were inserted and activated with a low dose of PMA (20 nM). Among group A PKCs, PKC alpha was the most effective activator of [3H]dopamine release (215%), followed by beta II (185%) and beta I (150%). PKC gamma had no consistent effect on neurotransmitter release. PC12 cells express PKC alpha and PKC beta, but not PKC gamma, as revealed by Northern-blot analysis. We therefore postulate that PKC alpha and PKC beta participate in neurotransmitter release, whereas PKC gamma might be involved in other neuronal functions. PMID- 1741759 TI - Cloning of cDNAs encoding a rabbit renal brush border membrane protein immunologically related to band 3. Sequence similarity with microsomal dipeptidase. AB - Distinct anion transport processes have been identified in the mammalian renal proximal tubule, but none of the responsible proteins or genes have been isolated. A 43 kDa rabbit microvillus membrane protein that is immunologically related to the erythroid anion exchanger (band 3) was a candidate for a renal anion transporter. To examine the structural relationship with band 3, we cloned cDNAs encoding the 43 kDa protein. The 43 kDa band-3-like protein was purified, and a novel sequence of 24 amino acids was obtained from the N-terminus. Degenerate oligonucleotides were synthesized based on this sequence, and the polymerase chain reaction with single-sided specificity was used to amplify and clone a 1330 bp cDNA from rabbit renal cortex. Additional overlapping 272 bp and 1123 bp cDNAs were obtained by synthesizing and screening a rabbit renal cortical cDNA library. The composite sequence was 1483 bp, terminated with (A)16, and was similar in size to the principal transcript expressed in rabbit renal cortex. The single long open reading frame was predicted to encode a protein composed of 410 amino acids with a molecular mass of 45,193 Da; 15 amino acids predicted to reside at the N-terminus were absent in the mature protein and may constitute a signal peptide. There was only limited sequence similarity with human erythroid band 3. Rather, the sequence was highly similar to microsomal dipeptidase, including the presence of a signal peptide and a consensus sequence for covalent linkage to glycosylphosphatidylinositol. In summary, the 43 kDa protein from rabbit renal cortex that is recognized by a monospecific antibody to erythroid band 3 is most likely a microvillus membrane dipeptidase. PMID- 1741760 TI - Structure-function relationships in the cysteine proteinases actinidin, papain and papaya proteinase omega. Three-dimensional structure of papaya proteinase omega deduced by knowledge-based modelling and active-centre characteristics determined by two-hydronic-state reactivity probe kinetics and kinetics of catalysis. AB - 1. A model of the three-dimensional structure of papaya proteinase omega, the most basic cysteine proteinase component of the latex of papaya (Carica papaya), was built from its amino acid sequence and the two currently known high resolution crystal structures of the homologous enzymes papain (EC 3.4.22.2) and actinidin (EC 3.4.22.14). The method used a knowledge-based approach incorporated in the COMPOSER suite of programs and refinement by using the interactive graphics program FRODO on an Evans and Sutherland PS 390 and by energy minimization using the GROMOS program library. 2. Functional similarities and differences between the three cysteine proteinases revealed by analysis of pH dependent kinetics of the acylation process of the catalytic act and of the reactions of the enzyme catalytic sites with substrate-derived 2-pyridyl disulphides as two-hydronic-state reactivity probes are reported and discussed in terms of the knowledge-based model. 3. To facilitate analysis of complex pH dependent kinetic data, a multitasking application program (SKETCHER) for parameter estimation by interactive manipulation of calculated curves and a simple method of writing down pH-dependent kinetic equations for reactions involving any number of reactive hydronic states by using information matrices were developed. 4. Papaya proteinase omega differs from the other two enzymes in the ionization characteristics of the common (Cys)-SH/(His)-Im+H catalytic-site system and of the other acid/base groups that modulate thiol reactivity towards substrate-derived inhibitors and the acylation process of the catalytic act. The most marked difference in the Cys/His system is that the pKa for the loss of the ion-pair state to form -S-/-Im is 8.1-8.3 for papaya proteinase omega, whereas it is 9.5 for both actinidin and papain. Papaya proteinase omega is similar to actinidin in that it lacks the second catalytically influential group with pKa approx. 4 present in papain and possesses a catalytically influential group with pKa 5.5-6.0. 5. Papaya proteinase omega occupies an intermediate position between actinidin and papain in the sensitivity with which hydrophobic interaction in the S2 subsite is transmitted to produce changes in transition-state geometry in the catalytic site, a fact that may be linked with differences in specificity in P2 S2 interaction exhibited by the three enzymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1741761 TI - Protein kinase C promotes arachidonate mobilization through enhancement of CoA independent transacylase activity in platelets. AB - A role for protein kinase C in arachidonate mobilization was demonstrated. Treatment of rat platelets with phorbol myristate acetate (PMA) or the diacylglycerol 1-oleoyl-2-acetylglycerol increased the transfer rate of arachidonate (AA) from phosphatidylcholine to phosphatidylethanolamine and stimulated AA release. The transfer dose-dependently induced by PMA was inhibited by staurosporine. Ether phospholipids were the acceptors of AA in these stimulated transfer reactions. Membrane-bound protein kinase C activity was enhanced by PMA, and this increase was inhibited by staurosporine. AA transfer between phospholipids is due to the action of polyunsaturated-fatty-acid-specific transacylases. For this purpose, transacylase activities were assayed in cell free systems from PMA-treated platelets. We observed that the CoA-independent transacylase activity was modulated in parallel to AA transfer as a function of PMA concentration. Taken together, the data show that protein kinase C activation might promote the mobilization of AA in platelets through the enhancement of CoA independent transacylase activity. PMID- 1741762 TI - Identification of the "major" polymorphic carbocysteine metabolite as S (carboxymethylthio)-L-cysteine. PMID- 1741763 TI - Immunochemical detection of covalently modified kidney proteins in S-(1,1,2,2 tetrafluoroethyl)-L-cysteine-treated rats. PMID- 1741764 TI - DNA damage, poly (ADP-ribosyl)ation and apoptotic cell death as a potential common pathway of cytotoxic drug action. AB - Although various anti-cancer drugs have widely differing primary modes of action, the mechanisms of cell death appear similar but are not well understood. To investigate this problem we exposed cultured human leukemic T-lymphoblasts to 1 hr pulse doses of an alkylating agent (mafosfamide) and a topoisomerase II inhibitor (etoposide) that cause delayed cell death. The effects of these drugs on nucleotide content, poly (ADP-ribosyl)ation and DNA strand breakage were assessed. Both drugs caused DNA strand breakage, and although the pattern differed, this seemed to be the major mechanism by which cells were killed. The degree and time course of the NAD and ATP depletion that mafosfamide and etoposide caused were similar. Both drugs caused a nadir in cellular nucleotide levels 2 hr after exposure but between 2 and 6 hr there was a partial recovery. This correlates with the time course of the DNA damage they caused and appeared to result from poly (ADP-ribosyl)ation. Both drugs were shown to cause apoptotic cell death associated with endonucleolytic DNA fragmentation. We suggest that DNA damage, as a primary or secondary effect, associated with poly (ADP-ribosyl)ation and apoptotic cell death may be a common pathway of cytotoxic drug action. PMID- 1741765 TI - Cytosol mediated metabolism of the experimental antitumor agent acridine carboxamide to the 9-acridone derivative. AB - The acridine antitumor agent N-[2'-(dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316; acridine carboxamide) is oxidized efficiently in vitro by rat and mouse hepatic cytosolic fractions. Under these conditions the oxidase activity has an apparent Km of 11 microM towards AC. A single product is formed which has been identified as the corresponding 9(10H)-acridone carboxamide by 1H NMR and mass spectrometry. Inhibition with menadione and amsacrine, but not allopurinol, indicates that this reaction is most likely to be catalysed by aldehyde oxidase (EC 1.2.3.1). Several AC analogues with modifications to the side chain (the N-oxide, N-monomethyl-, and amino-derivatives) are also metabolized to the equivalent acridone product but the 7-hydroxylated and 4 carboxylic acid acridine derivatives are not. PMID- 1741766 TI - The biochemical pharmacology of the thymidylate synthase inhibitor, 2-desamino-2 methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583). AB - 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a more water-soluble analogue of the quinazoline-based thymidylate synthase (TS) inhibitor, N10-propargyl-5,8-dideazafolic acid (CB3717). A 3-fold loss in TS inhibitory activity (murine and human TS, Ki = 10 nM) was accompanied by a 40 fold increase in growth inhibitory potency against L1210 and W1L2 cells in vitro (IC50 = 0.085 and 0.05 microM, respectively) when compared with CB3717. In L1210 cells a concentrative uptake mechanism was demonstrated for [3H]ICI 198583 (Kt = 2.9 microM). The L1210:1565 cell line, with an impaired ability to transport reduced folates or methotrexate (MTX), was resistant (100-fold relative to the wild-type L1210 line) to ICI 198583 (but not CB3717) and did not take up [3H]ICI 198583 significantly. The measurement of folylpolyglutamate synthetase (FPGS) substrate activity demonstrated a Km of 40 microM for ICI 198583 and a Vmax/Km (relative to folic acid) of 3.5. The formation of intracellular polyglutamate derivatives was demonstrated in both L1210 (mouse) and WIL2 (human) cells grown in vitro after exposure to 1 microM [3H]ICI 198583. In L1210 cells, by 4 hr, approximately 50% of the intracellular 3H(approximately 1 microM) was found as polyglutamate forms of ICI 198583, principally as tri- and tetraglutamates. After 24 hr the ICI 198583 polyglutamate pool had expanded, the tetraglutamate metabolite predominated and there was significant formation of the pentaglutamate. Upon resuspension of L1210 cells in drug free medium, ICI 198583 was largely lost from the cells but the polyglutamates were preferentially retained, after 24 hr approximately 70% remained. Synthetic ICI 198583 polyglutamates were shown to be up to 100-fold more potent as inhibitors of isolated TS than the parent compound. Following in vivo administration (500 mg/kg i.v.) ICI 198583 was cleared rapidly from the plasma of mice (T1/2 beta = 16 min, clearance = 42 mL/min/kg). Despite this clearance there was prolonged, dose dependent inhibition of TS in L1210:NCI cells in vivo. Thus, following 500 mg/kg i.v. the flux through TS was inhibited by greater than 80% for at least 24 hr. Administration of five doses at 5 mg/kg daily of ICI 198583 to L1210:ICR tumour bearing mice resulted in greater than 60% of the mice being cured, a 10-fold improvement in potency over CB3717. The maximum tolerated dose (MTD) for ICI 198583 using this schedule was greater than 500 mg/kg/day compared with 200 mg/kg/day of CB3717.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1741767 TI - A survey of vasoactive peptide metabolizing enzymes in the rat mesenteric arterial bed perfusate. AB - We have demonstrated that the isolated perfused rat mesenteric arterial bed (MAB) secretes peptidases capable of metabolizing bradykinin and angiotensin I. The major degradative pathway of bradykinin by enzymes found in the rat MAB perfusate was mediated by carboxypeptidase A-like activity, whereas angiotensin 1 degradation followed two main routes, one attributable to a carboxypeptidase A like enzyme and the other to an endopeptidase. This latter enzyme seems to be a novel serine peptidase capable of releasing angiotensin II directly from both angiotensin I and renin substrate tetradecapeptide. The rat MAB perfusate was also shown to contain additional endo- and exopeptidases that might play a role in the metabolism of other vasoactive peptides. Our finding that isolated rat MAB secretes peptidases into the perfusion medium indicates that peptide processing within the microvasculature environment may be effected by enzymes besides those normally found in plasma or associated with cell membranes. PMID- 1741768 TI - Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs- II. Racemization and hydrolysis of (R)- and (S)-ibuprofen-CoA thioesters. AB - The inversion of 2-arylpropionic acids (2-APAs) has become the subject of much attention. It is a unique reaction specific to this group of drugs. Inversion proceeds via stereoselective activation of the R-enantiomer to its CoA thioester whereby it is then racemized and hydrolysed to release free drug. The racemization and hydrolysis processes have been examined in this study using chemically synthesized CoA thioesters of the ibuprofen enantiomers and in vitro models employing rat liver homogenate and the mitochondrial and microsomal fractions as the source of the 'racemase' enzymes. Rat liver homogenate mediated the racemization and hydrolysis of both (R)- and (S)-ibuprofen-CoA thioesters. The rat liver mitochondrial fraction similarly mediated racemization and hydrolysis of both CoA thioesters. There was less racemase activity in the rat liver microsomal fraction and the data indicated that this fraction may contain two hydrolases which act separately on the (R)- and (S)-ibuprofen-CoA thioesters. The data are further evidence that the stereoselectivity of the CoA synthetase controls the overall stereoselectivity of inversion. PMID- 1741769 TI - Induction by perfluorooctanoic acid of microsomal 1-acylglycerophosphocholine acyltransferase in rat kidney. Sex-related difference. AB - Response of rat kidney to the challenges by perfluorooctanoic acid (PFOA) was studied using microsomal 1-acyglycerophosphocholine (1-acyl-GPC) acyltransferase as a parameter. Marked induction of the enzyme was brought about in kidney of male rats, whereas the induction in kidney of female rats was far less pronounced. The sex-related difference in the response of kidney to PFOA was much more marked than those seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethy-lenedithio)diethanol (tiadenol). Hormonal manipulations revealed that the sex-related difference in the response of kidney to PFOA was strongly dependent on the state of gonadal hormones of rats. Even after a prolonged administration of PFOA for up to 26 weeks, this sex-related difference was still evident. Induction of peroxisomal beta-oxidation was brought about concurrently with microsomal 1-acyl-GPC acyltransferase and a high correlation was confirmed between the inductions of these two parameters. PMID- 1741770 TI - Allosteric regulation of cloned m1-m5 muscarinic receptor subtypes. AB - Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subtype to more than 60 min for the m5 subtype. For [3H]QNB, half-times (at 37 degrees) ranged from 1 hr (m2) to almost 4 hr (m3). The presence of gallamine slowed the dissociation of [3H]NMS from all of the subtypes, with an order of potency of m2 greater than m4 greater than m1 greater than m3 greater than m5. Dissociation of [3H]QNB from m1 and m2 receptors was modulated by gallamine in the biphasic manner that we have described previously for cardiac receptors; that is, low concentrations (1-10 microM) of gallamine accelerated dissociation, while 1 mM gallamine slowed it. Verapamil slowed the dissociation of [3H]-QNB from the m2 receptor in a monophasic manner, while the action of d-tubocurarine was qualitatively similar to that of gallamine. The potency of gallamine in allosterically regulating the m2 receptor was inversely related to ionic strength. Inactivation of pertussis toxin-sensitive G proteins abolished the ability of guanine nucleotides to regulate agonist affinity at the m2 receptor, but had no effect on allosteric regulation of the m2 receptor. These findings indicate that susceptibility to allosteric regulation varies in a complex way across muscarinic receptor subtypes and according to the choice of ligand. PMID- 1741771 TI - Structure and expression of the cytosolic aldehyde dehydrogenase gene in cyclophosphamide-resistant murine leukemia L1210 cells. AB - These investigations were performed to clarify the molecular basis for the enhanced expression of cytosolic aldehyde dehydrogenase (ALDH-1) enzymatic activity in the cyclophosphamide-resistant L1210/CPA murine leukemia cell line, as compared to the parental L1210/O strain. Western immunoblot analysis was performed using a 15-fold greater quantity of cytosolic protein from the L1210/O as compared to the L1210/CPA cell line. Nevertheless, ALDH-1 immunoreactive protein could be detected only in the L1210/CPA cells. Northern analyses, performed using total cellular and polyadenylated RNA, again demonstrated ALDH-1 specific transcripts only in the L1210/CPA cell line. This transcript was identical in size to the ALDH-1 message expressed by normal murine hepatocytes. On Southern analysis, no evidence of gene amplification, gene rearrangement, or significant mutations of length was detected. These studies suggest that the ALDH 1 protein produced by the L1210/CPA cell line is structurally normal. Moreover, overexpression of the gene does not appear to have arisen as a result of an incremental process, such as gene amplification. Rather, a qualitative abnormality in the regulation of this gene appears to exist in the L1210/CPA cells, which distinguishes them from L1210/O cells and from normal murine lymphocytes. PMID- 1741772 TI - Perturbation of the fluidity of the erythrocyte membrane with ionophoric antibiotics and lipophilic anaesthetics. AB - The fluidity of the rat erythrocyte membrane was evaluated by measurement of excimer fluorescence of an intra-molecular forming fluorophore, 1,3-di(1 pyrenyl)propane. The polyene ionophoric antibiotics, amphotericin B and nystatin, were found to fluidize the erythrocyte membrane, as assessed by the increase in the excimer/monomer fluorescence intensity ratio, by 42 and 13%, respectively, compared with control samples. In contrast, of the peptide ionophoric antibiotics, valinomycin demonstrated about twice the effect which gramicidin A had on depressing the fluidity of the erythrocyte membrane. On the other hand, the general lipophilic anaesthetics, propanidid and althesin, led to an increase, by 70 and 32%, respectively, while the local anaesthetic, procaine, led to a decrease by 20%, in the fluidity of the erythrocyte membrane. These results were explained in the light of the partition coefficients determined for these drugs in decane and native membranes, their affinities for specific membrane components and the changes which they induce in the permeability properties of erythrocyte and other biological membranes. PMID- 1741773 TI - Problems with the measurement of monoamine oxidase A protein concentration in mitochondrial preparations. Revised molecular activities and implications for estimating ratios of MAO A:MAO B molecules from radiochemical assay data. AB - There are significant discrepancies in the literature concerning the concentration of monoamine oxidase A (MAO A) from a number of tissue sources. Therefore, we compared the two principal techniques that have been used for quantitation of MAO A protein concentration: (1) titration of the enzyme with the MAO A-selective inhibitor clorgyline, and (2) saturation of the enzyme with [3H] pargyline followed by immunoprecipitation with an MAO A-specific monoclonal antibody. To determine which of the two techniques was likely to yield more reliable values for MAO A, MAO A protein concentrations in the same preparations were determined by quantitative immunoblotting. [3H]Pargyline binding and quantitative immunoblotting yielded comparable values which were markedly lower than those obtained by titration of MAO A with unlabeled clorgyline. Therefore, clorgyline titration can seriously overestimate the concentration of MAO A protein in mitochondrial preparations. Since many literature values for the molecular activity of MAO A have relied upon enzyme concentrations determined by clorgyline binding, we reevaluated the molecular activities of MAO A and B for five important substrates. The ratio, MAO A molecular activity:MAO B molecular activity decreased in the order: serotonin (35:1) greater than tryptamine (12:1) greater than tyramine (3.3:1) greater than dopamine (2.4:1) greater than benzylamine (1:23). No comparable ratio was determined for beta-phenylethylamine because of its previously described substrate inhibition of MAO B, although it is oxidized faster by MAO B over a wide range of concentrations. Comparison of molecular activities and Km values for MAO A and B showed that with the exception of benzylamine and beta-phenylethylamine, MAO A oxidizes the other tested substrates faster than MAO B over a wide range of concentrations. Therefore, measured ratios of MAO A:MAO B activity are generally greater than the ratios of MAO A:MAO B molecules in the preparations. PMID- 1741774 TI - Menadione-induced DNA damage in a human tumor cell line. AB - The nature and extent of menadione (MD)-induced DNA damage were explored using the human breast cancer cell line MCF-7. Concentration-dependent single-strand (ss) and double-strand (ds) DNA breaks were detected in MD-treated MCF-7 cells using the alkaline- and neutral-elution techniques, respectively. The repair of ss and ds DNA breaks was extensive but not complete after a 6-hr incubation in drug-free medium. Evidence was found for the production of DNA interstrand cross links in MCF-7 cells treated with the bifunctional alkylating agent, mitomycin C, but not for cells treated with MD. Exposure of MCF-7 cells to etoposide (VP-16), mitoxantrone and camptothecin resulted in the detection of significant amounts of protein-linked DNA breaks, whereas none were found in MD-treated cells. These results support the proposition that MD-induced DNA damage is not likely to be mediated via topoisomerases, nor do significant amounts of protein-linked DNA form in MD-treated cells. Thus, MD serves as a good model for examination of the role of the quinone moiety in DNA damage in relation to redox cycling. Future studies directed at elucidation of the biochemical determinants mediating formation of reactive oxygen species effecting the MD-induced DNA damage are necessary and underway. PMID- 1741775 TI - Questioning the reliability of p-nitrophenyl-beta-D-xyloside as probe to study the metabolic effects of abrogated proteoglycan synthesis in cultured cells. AB - p-Nitrophenyl-beta-D-xylopyranoside (PNP-Xyl) and similar aglycone derivatives of xylosides are proposed selective inhibitors of proteoglycan synthesis which are used frequently to analyse the metabolic and cellular effects of abrogated proteoglycan formation and, hence, tentatively, the functions of these complex molecules. Using rat liver fat storing cell (FSC) cultures as a model, the possibility was tested that p-nitrophenol (PNP), which might be generated by the enzymatic hydrolysis of PNP-Xyl, could mediate some of those effects ascribed previously to PNP-Xyl induced inhibition of proteoglycan synthesis. PNP-Xyl and PNP inhibited dose-dependently the proliferation of FSC reaching 50% inhibition at about 1.9 and 0.6 mM, respectively. The inhibition of proliferation was not accompanied by signs of toxic cell damage and was fully reversible after withdrawal of the drugs. After an initial 4-fold stimulation of the formation of [35S]sulfate-labeled medium glycosaminoglycans (GAG) by PNP-Xyl at 0.1 mM, higher concentrations of this compound (about 0.5 mM) but also PNP decreased progressively the synthesis of sulfated medium GAG. A proliferation inhibiting concentration of PNP (0.75 mM) induced disorganization and reduced the expression of desmin- and smooth muscle iso-alpha-actin containing cytoskeletal filaments. These effects were similar to related effects reported previously for PNP-Xyl. Incubation of FSC with 5 mM PNP-Xyl resulted in a time-dependent increase of PNP in medium and cells; intracellular concentrations of PNP were reached sufficient to inhibit the mitotic activity of FSC. In lysates of FSC 0.65 nmol PNP/hr/micrograms DNA or 1 x 10(5) cells were generated from PNP-Xyl (5 mM) added as substrate. Exemplified with PNP-Xyl-treated FSC cultures, the results suggest for other cell and organ systems also that PNP, which is enzymatically cleaved from PNP-Xyl, might mediate at least some of the major effects attributed previously to the inhibition of proteoglycan synthesis. The aglycone may interfere with the effects of PNP-Xyl on proteoglycan metabolism and, therefore, could complicate in an unpredictable manner the interpretation of metabolic inhibitory studies using these compounds. PMID- 1741776 TI - Mechanistic aspects of uptake and sinusoidal efflux of dibromosulfophthalein in the isolated perfused rat liver. AB - Using the isolated perfused rat liver technique we examined whether the accumulation and sinusoidal efflux processes of the organic anion dibromosulfophthalein (DBSP) are dependent on the intracellular ATP content, chloride concentration in the perfusion medium as well as temperature of the medium and whether they are mediated by the same or by separate carrier mechanisms. The net sinusoidal efflux rate, being the resultant of sinusoidal efflux and re-uptake, was decreased more than 50% after lowering the medium temperature from 37 to 26 degrees indicating that the efflux process is carrier mediated. The uptake rate was decreased only 18% after lowering the medium temperature to 26 degrees. Lowering of the hepatic ATP content for more than 80% clearly decreased the DBSP uptake rate but not the sinusoidal efflux rate. These observations indicate that these opposing transport steps probably are mediated by two separate carriers. Additional evidence for this hypothesis originated from the observation that sinusoidal efflux of DBSP was decreased about 30% whereas hepatic uptake of the substrate remained unaltered after replacing chloride in the perfusion medium with gluconate. In summary, we conclude that uptake and sinusoidal efflux of DBSP are mediated by two separate carrier systems that are influenced differently by ATP depletion, temperature lowering and presence of Cl gradients. PMID- 1741777 TI - Differential inhibition of epidermal growth factor binding by photoactivated psoralens and the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in cells overexpressing protein kinase C. AB - A rat fibroblast cell line, R6PKC3, that stably overexpresses the beta-1 form of protein kinase C was used to analyze sensitivity to inhibitors of epidermal growth factor (EGF) binding. R6PKC3 cells overexpress protein kinase C activity 53-fold relative to non-overexpressing control R6C1 cells. Inhibition of EGF binding by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) and photo-activated psoralens was compared in these cells. We found that 125I-EGF bound both of the cell lines and was rapidly internalized in a temperature dependent process and metabolized. Binding of EGF to the R6 cells overexpressing protein kinase C was markedly less than binding to R6C1 control cells. In both of the cell lines, TPA and photoactivated psoralens inhibited 125I-EGF binding but the response of these cells to these inhibitors was distinct. R6PKC3 cells were markedly more sensitive to TPA and were resistant to recovery from TPA-induced inhibition of 125I-EGF binding when compared to control cells. These differences were not observed in other subclones of cells overexpressing protein kinase C, suggesting that they may be unique to R6PKC3 cells. In contrast, no major differences in sensitivity to photoactivated psoralens were observed in R6C1 and R6PKC3 cells. These data indicate that TPA and photoactivated psoralens inhibit 125I-EGF binding to these cell lines by distinct mechanisms. PMID- 1741778 TI - Mode of action of the lanthionine-containing peptide antibiotics duramycin, duramycin B and C, and cinnamycin as indirect inhibitors of phospholipase A2. AB - Effects of the lanthionine-containing peptide antibiotics duramycin, duramycin B, duramycin C and cinnamycin on the activity of phospholipase A2 from six different sources were studied, and their mode of action was investigated. The four antibiotics inhibited potently all tested phospholipases A2, with IC50 values of around 1 microM, using phosphatidylethanolamine or [1-14C]oleate-labelled Escherichia coli, whose phospholipids are rich in phosphatidylethanolamine, as substrates. No inhibition was observed when the substrate was phosphatidylcholine. Binding of the antibiotics to the lipid fraction of E. coli could be demonstrated by co-sedimentation with whole, but not with lipid-depleted E. coli. In addition, preincubation of duramycin B with vesicles of phosphatidylethanolamine, but not those of phosphatidylcholine, prevented the inhibition of phospholipase A2 activity. The interaction of duramycin B and C, but not that of the biologically inactive compounds actagardine and the duramycin B trisulphoxide, with phosphatidylethanolamine was demonstrated using circular dichroism studies. On the other hand, no interaction of duramycin B with phosphatidylcholine could be demonstrated. A strict correlation between the physico-chemical interaction of the studied lantibiotics, demonstrated by circular dichroism spectroscopy, and their inhibition of phospholipase A2 was observed. These results suggest that lanthionine-containing peptide antibiotics inhibit phospholipase A2 indirectly by specifically sequestering the substrate phosphatidylethanolamine. This mode of action is analogous to the one described for the protein lipocortin. PMID- 1741779 TI - Effect of cholesterol supplementation on acetylcholinesterase activity from sheep platelet plasma membrane. PMID- 1741780 TI - A second site of action of soman on acetylcholinesterase. PMID- 1741781 TI - Enhancement of cross-linking of presynaptic plasma membrane proteins by phospholipase A2 neurotoxins. PMID- 1741782 TI - Potentiation of the inductive effect of phenobarbital on cytochrome P450 mRNAs by cannabidiol. PMID- 1741783 TI - Effect of cyclosporin A in vivo on taurocholate uptake by rat hepatocytes. PMID- 1741784 TI - In vitro effect of clofibric acid derivatives on rat hepatic microsomal electron transport chains. PMID- 1741785 TI - A quick method for detecting metabolic cooperation. PMID- 1741786 TI - Anti-neoplastic glucuronide prodrug treatment of human tumor cells targeted with a monoclonal antibody-enzyme conjugate. PMID- 1741787 TI - Contracting speech-language pathology services to Medicare providers. PMID- 1741788 TI - Communicating with people who have multiple sensory impairments. AB - The good news is that we can be effective teachers, clinicians, interactors, and consultants, enabling the learner, ourselves, and significant others to communicate more effectively with one another. The bad news is that we can be ineffectual, often leading the learner to learned helplessness, prompt dependency, and possibly self-injurious behaviors. Extreme measures may be the only means that we have given the learner to communicate intents such as, "Stop intruding on my space," or "Come attend to me." We can set ourselves and the learner up for success or for failure. We, as service providers, have choices and options as well. PMID- 1741789 TI - Visual assessment of people who are deaf. The essential role of audiologists and speech-language pathologists. PMID- 1741790 TI - Audiological services. Meeting the needs of people who are deaf and blind. PMID- 1741791 TI - Treating behavior problems with communication. PMID- 1741792 TI - New methods for evaluating vision. PMID- 1741793 TI - The Federal Government's role in educating people with dual sensory impairments. PMID- 1741794 TI - School-to-work transition for youth who are both deaf and blind. AB - Transition, collaborative planning for desired adult opportunities, and implementation of objectives and activities can increase the postsecondary employment opportunities open to youth who are deaf and blind. Collaborative transition planning is characterized by family-professional partnerships in developing visionary personal profiles, systematic and transdisciplinary vocational preparation in community-based settings, and infusion of related services within educational programs. PMID- 1741795 TI - Giving birth to ASHA's special interest divisions. A look at early developmental milestones. PMID- 1741796 TI - Getting in shape: lean cuisine for the '90s. AB - The results of the 1991 Omnibus Survey suggest that members of ASHA exhibit a complex sensitivity to the economic environment. On the one hand, budget sizes for equipment and supplies have decreased, and professionals are working longer hours to provide needed services to clients/patients. On the other hand, employment within the professions of speech-language pathology and audiology remains strong. Clearly, even in times of fiscal uncertainty, few individuals want to forego or delay needed health care services. Data from the survey indicated that our professionals may be adapting their work patterns to meet society's needs, using less fiscal and human resources. Hopefully, the years ahead will bring about positive economic growth and the speech-language pathology and audiology professions will have profited from innovative solutions developed during these lean years to maintain high quality care on tight budgets. PMID- 1741797 TI - Children of poverty. What is their future? PMID- 1741798 TI - Research funding for speech-language-hearing: FY 1990 update. PMID- 1741799 TI - Mammography and malpractice. PMID- 1741800 TI - Propofol does not trigger malignant hyperthermia. PMID- 1741801 TI - Should drugs be legalized? Implications of the debate for the mental health field. PMID- 1741802 TI - The value of arthrography in the decision-making process regarding surgery for internal derangement of the temporomandibular joint. AB - In this study, the clinical and arthrographic findings from 43 internally deranged temporomandibular joints (TMJs) were compared with the intra-surgical observations. In 40 of 43 joints, arthrography did not provide any additional information useful for diagnosis or treatment. In six joints, the problem was misdiagnosed. Only in three joints did arthrography demonstrate the existence of perforation in the posterior attachment that had not been suspected during the clinical examination. Because of the doubtful importance of arthrographic information for the decision-making process, it is suggested that the method be applied only in cases in which clinical examination and plain radiographs have failed to uncover the signs and symptoms indicative of a TMJ disorder. PMID- 1741803 TI - Eukaryote origins. Seeds of a universal tree. PMID- 1741804 TI - Complication of continuous spinal microcatheters: should we seek their removal if sheared? PMID- 1741805 TI - A sticking flutter valve. PMID- 1741806 TI - Duration of intravenous fluid replacement after abdominal surgery: a prospective randomised study. AB - This prospective randomised study examined the possibility of early resumption of oral hydration and discontinuation of intravenous fluid replacement after emergency or elective abdominal surgery. Following elective cholecystectomy alone or with a choledocholithotomy or an emergency Hartmann's procedure for large bowel obstruction, patients were randomised to early oral hydration (sips of water for 12 h followed by free fluids by mouth for 24 h, when oral intake of food was allowed--intravenous hydration was discontinued 6 h after starting the intake of free fluids orally) or conventional intravenous hydration (intravenous hydration and an oral regimen of water as follows: sips every hour for 12 h, 30 ml every hour for 24 h, 60 ml every hour for 24 h, 90 ml every hour for 24 h, free fluids for 12 h, when food was allowed--intravenous hydration was discontinued 6 h after starting the free fluids). The two regimens were equally effective in maintaining fluid balance and normal plasma and urinary electrolytes without any observed differences in biochemical or metabolic values. Each of free fluids by mouth, discontinuation of intravenous hydration, and consumption of solid food were achieved in the patients on early oral hydration at time periods significantly shorter than those attained with the conventional regimen (P less than 0.001). Similarly, patients on the latter regimen were hospitalised for significantly longer times than those on early oral hydration (P less than 0.001). Early oral hydration after biliary surgery or a Hartmann's procedure effectively maintains fluid balance and has advantages over the conventional intravenous hydration regimen. PMID- 1741807 TI - Two kinds of diverticular disease. AB - Two kinds of acquired diverticular disease were identified. The more common variety presented with pain, bowel symptoms or fistulae, and the less common with bleeding. The former patients rarely had a history of bleeding and among the latter pain and bowel symptoms were uncommon. In contrast to the few, chiefly sigmoid, diverticular often found in the former group, barium enemas of those presenting with bleeding usually showed densely packed and extensive diverticula. Even where there was no history suggesting perforation or evidence of it at operation, specimens resected for the more common form of diverticular disease invariably showed histological evidence of previous perforation. There was no histological evidence of previous perforation in those specimens resected for bleeding. This retrospective clinical, radiological and histological study supported the idea that there are two kinds of diverticular disease, one associated with perforation and its sequelae, the other associated with bleeding. PMID- 1741808 TI - Judgment strategies for coping with ambiguous clinical situations encountered in primary health care [corrected]. AB - This naturalistic study identifies and describes strategies for clinical problem solving in situations of uncertainty, from observations of patient/family visits in a family health center. Judgment strategies were described for four types of uncertainty: information, diagnosis, treatment, and patient response that roughly correspond to the phases of assessment, planning, implementation, and evaluation of the clinical problem-solving process. The study contributes to increased understanding of the practical (experiential) knowledge involved in clinical judgment. PMID- 1741809 TI - The patient with noncardiogenic pulmonary edema. AB - Based on the content of this article, the reader should be able to (1) identify the differences between cardiogenic and noncardiogenic pulmonary edema (NCPE); (2) identify the most common causes of airway obstruction leading to pulmonary edema; (3) state the mechanism of action for the development of NCPE following laryngospasm; (4) state the signs and symptoms of NCPE; (5) identify the treatment for NCPE; and (6) state three nursing actions that are indicated in the care of the patient with NCPE. PMID- 1741810 TI - Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme. AB - Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall. PMID- 1741811 TI - Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. AB - This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis. PMID- 1741812 TI - Calcium ions and sperm. PMID- 1741813 TI - Sustained plasma concentrations of fluoxetine and/or norfluoxetine four and eight weeks after fluoxetine discontinuation. PMID- 1741814 TI - Bend force systems. PMID- 1741815 TI - Identity of Pltgp40 and lysomal integral membrane protein-CD63. PMID- 1741816 TI - Dietary fat and breast cancer. PMID- 1741817 TI - Plastid origins. PMID- 1741818 TI - Posttraumatic stress disorder in World War Two veterans. AB - The clinical presentations of chronic posttraumatic stress disorder of 18 world war two veterans are detailed. This psychiatric sequelae of trauma may be chronic and persistent, as demonstrated by the presence and severity of symptoms 45-50 years after the onset. Early treatment interventions would appear desirable even if not yet conclusively proven to be effective. PMID- 1741819 TI - Cervical samplers. PMID- 1741820 TI - Pseudodepression in hyponatremia. PMID- 1741821 TI - Same day testing for HIV. PMID- 1741822 TI - Perinatal bereavement. PMID- 1741823 TI - Chronic fatigue syndrome. PMID- 1741824 TI - Treatment of intestinal cryptosporidiosis with zidovudine and SMS 201-995, a somatostatin analog. PMID- 1741825 TI - Re: The Role of Chemical Peeling in the Treatment of Photodamaged Skin. J Dermatol Surg Oncol 1990; 16:945-54. PMID- 1741826 TI - Pulmonary disease and congestive heart failure. PMID- 1741827 TI - The use of dexamethasone in premature infants at risk for bronchopulmonary dysplasia or who already have developed chronic lung disease: a cautionary note. PMID- 1741828 TI - Infamous acuity system. PMID- 1741829 TI - Aspiration pneumonia and the laryngeal mask airway. PMID- 1741831 TI - Transcholecystic operative cholangiography: an alternative technique. PMID- 1741830 TI - Pulmonary edema of environmental origin--newer concepts. PMID- 1741832 TI - Duration of intravenous fluid replacement after abdominal surgery: a prospective randomised study. PMID- 1741833 TI - Is diet important in rheumatoid arthritis? PMID- 1741834 TI - Nd:YAG laser bronchoscopy: rigid or fiberoptic mode? PMID- 1741835 TI - Caffeine and aggression. PMID- 1741836 TI - Platelet aggregation in Raynaud's phenomenon. PMID- 1741837 TI - The care of a patient with noncardiogenic pulmonary edema. PMID- 1741838 TI - Cocaine and cerebral atrophy. PMID- 1741839 TI - AIDS and insurer discretion. PMID- 1741840 TI - Histologic atypia in clinically benign nevi. PMID- 1741841 TI - Neurosyphilis and human immunodeficiency virus infection. PMID- 1741842 TI - Radiation-induced optic neuropathy. PMID- 1741843 TI - Prostitutes, workers and kidneys: Brecher on the kidney trade. AB - Brecher argues that the practices of selling blood and kidneys are akin to the practices of prostitution and wage-labour since they all involve commodification and, by implication, should be subject to legal prohibition. I suggest that these practices need not involve commodification and that they should only be condemned if people are forced into them because of their lack of power. Rather than these practices being prohibited, I suggest that it would be preferable if they were subject to state regulation in order to protect the weak from exploitation. PMID- 1741844 TI - Amyloidosis. PMID- 1741845 TI - Toward more rational nerve conduction interpretations: the effect of height. PMID- 1741846 TI - Use of isometric exercise testing can replace isotonic testing to detect and evaluate hypertensive populations. PMID- 1741847 TI - Maverick nursing? PMID- 1741848 TI - Rapid enzyme-linked immunoassay tests for group B streptococcus infection. PMID- 1741849 TI - The supraglottic oropharyngeal airway. PMID- 1741850 TI - Measurement and manipulation of pulmonary artery wedge pressure in adult respiratory distress syndrome. PMID- 1741851 TI - Correction of fructosamine values for total protein during pregnancy. PMID- 1741852 TI - Comments on "Moebius syndrome: animal model--human correlations and evidence for a brainstem vascular etiology". PMID- 1741853 TI - Acquired immunodeficiency syndrome and critical care. PMID- 1741854 TI - Battery of assays for detecting chemical inhibition of gap junctional intercellular communication GJIC. PMID- 1741855 TI - Conjugation of phenols in human colonocytes. PMID- 1741856 TI - Healing or killing? PMID- 1741857 TI - Coaptation of anterior rami of C-3 and C-4. PMID- 1741858 TI - Callosotomy for seizures. PMID- 1741859 TI - Urodynamics simplified. PMID- 1741860 TI - Cardiorespiratory effects during gastrointestinal endoscopy. PMID- 1741861 TI - An approach to spinal or epidural catheters that are difficult to remove. PMID- 1741862 TI - Tumour surgery of the head and neck. PMID- 1741863 TI - Intravaginal prostaglandin E2 gel and cardiovascular changes in hypertensive pregnancies. AB - Prostaglandin E2 (PGE2) and its analogues may be potent vasodilators, and intravaginal PGE2 is known to be absorbed rapidly into the maternal circulation. This study investigated any cardiovascular effects from intravaginal PGE2 on 42 hypertensive pregnant women requiring preinduction cervical ripening. Declines in maternal diastolic, systolic, and mean arterial pressures were apparent during the first half hour. This trend was mild, was reversible without treatment, and did not influence the fetal heart rate baseline or patterns. Fear of clinically significant changes should not be a concern, but monitoring during the first hour is recommended. PMID- 1741864 TI - Fibroepithelial polyps of the vagina in pregnancy. AB - A 38-year old pregnant woman presented with a polypoid tumor of the vagina. A biopsy revealed benign fibroepithelial polyps. Her pregnancy progressed normally, and she underwent an uncomplicated vaginal delivery. Once the benign nature of the lesion has been established, a spontaneous vaginal delivery is not contraindicated. However, operative vaginal delivery should be avoided to reduce the risk of trauma and hemorrhage. Local excision is curative and may be performed as an interval procedure when the vaginal vascularity has returned to normal. PMID- 1741865 TI - Umbilical artery flow velocity waveforms and cord blood viscosity. AB - The role of cord blood viscosity in determining the umbilical artery Doppler flow velocity waveform (FVW) was investigated in 22 normal pregnancies and 29 complicated pregnancies. FVWs were quantified by calculating the pulsatility index (PI). There was a significant correlation between an abnormal PI (more than 2 SD from the mean) and fetal growth retardation (less than 5th birthweight centile), cesarean section for fetal distress, and raised cord blood hematocrit. However, there was no relationship between whole blood or plasma viscosity measurements and the umbilical artery PI. PMID- 1741866 TI - Prenatal diagnosis of the aneurysm of the vein of Galen by pulsed Doppler unit. AB - Aneurysm of the vein of Galen is a rare anomaly. In the severe type, the first clinical manifestation of this anomaly is heart failure after birth. Prenatal diagnosis is important in preventing heart failure during the postnatal period. Here, we report the prenatal diagnosis of a case of aneurysm of the vein of Galen in which we used a pulsed Doppler unit combined with a fetal electrocardiogram phonocardiogram unit. PMID- 1741867 TI - Grading of left-to-right shunting ductus arteriosus in neonates with bedside pulsed Doppler ultrasound. AB - A nonimaging pulsed Doppler technique was used to grade the magnitude of flow in left-to-right shunting ductus arteriosus. The results were compared with those obtained with a color Doppler flow mapping technique. The correlation between the grading results by these two methods was 0.91 (p less than 0.01). To determine hemodynamic influence of left-to-right shunting ductal flow, simultaneous measurements of Doppler-derived cardiac output were done. Results showed significantly higher cardiac output in infants with grade III shunting than in infants with grade 0 and grade I shunting. The nonimaging pulsed Doppler ultrasound technique used in the present study proved to be a clinically useful and accurate grading system of left-to-right shunting at the ductal level. The simple grading system with nonimaging Doppler is a valuable adjunct to the color Doppler flow mapping technique. It allows a regular evaluation of ductal flow as well as cardiac output. PMID- 1741868 TI - Antenatal diagnosis of a rare combined fetal malformation: acardius acephalus and single ventricle of the twin. AB - The development of an acardius in a monozygotic multiple pregnancy has been reported in more than 200 cases. We present the case of an acardius acephalus in a twin pregnancy additionally complicated by a serious cardiac malformation of the donor twin (single ventricle). Antenatal diagnosis and development as well as intrauterine treatment of the donor twin from 26 to 34 weeks of gestation are described. PMID- 1741869 TI - Management of prenatally detected nonlethal fetal anomalies: is a karyotype of benefit? AB - The pregnancy outcomes of 155 women who underwent an amniocentesis for a prenatal karyotype after being diagnosed by ultrasound as having one or more nonlethal structural anomalies are presented. Thirty-three (21%) patients were found to have an abnormal karyotype. Knowledge of the prenatal karyotype was useful in the subsequent management of these pregnancies. A pregnancy with a fetal anomaly diagnosed prior to 24 weeks was more likely to be terminated if an abnormal karyotype was also present. In women who were diagnosed as having a fetal anomaly with an abnormal karyotype at 24 weeks or later, only 3 of 13 (23%) infants survived the neonatal period. Knowledge of the karyotype results influenced decisions regarding the place, timing, and route of delivery in these fetuses. In 32 women, (21%) a karyotype was beneficial by avoiding maternal transport, cesarean delivery, and neonatal expenses at a Level III perinatal center. PMID- 1741870 TI - Prenatal sonographic features and management of a fetus with Roberts-SC phocomelia syndrome (pseudothalidomide syndrome) and pulmonary hypoplasia. AB - The Roberts-SC phocomelia syndrome (pseudothalidomide syndrome) is a rare, usually lethal condition involving short limbs and occasional hydrocephalus. Presented is a case in which prenatal sonographic findings were highly suggestive of this syndrome, although not definite. In this fetus, findings of hydrocephalus, short limbs, and probable pulmonary hypoplasia changed the intrapartum management. The findings, correlated with the postmortem radiography, led to diagnosis of probable Roberts-SC syndrome. PMID- 1741871 TI - Ranged-gated pulsed Doppler of the umbilical artery in human fetuses during normal pregnancies. AB - Range-gated pulsed Doppler has permitted the study of umbilical artery flow velocity waveforms (FVWs) in human fetuses and is becoming part of the antepartum fetal evaluation. No uniform method of describing such velocity waveforms and no significant body of normal values using pulsed Doppler can be found in the literature. The present study reports on a cohort of 268 patients who had pulsed Doppler umbilical artery FVWs performed during their pregnancy. The gestational age at the time of the study ranged between 16th and 42nd weeks of gestation in normal pregnancies. The systolic to diastolic (S/D) ratio was found progressively to decrease as gestation advanced; however, the range of normal values in this study was found to be quite large at all gestational ages. The present data represent normative data of the umbilical artery FVWs S/D ratio in a large number of normal pregnancies as shown by the follow-up of all the patients to delivery. Before umbilical artery waveform becomes part of the antenatal armamentarium, we advise caution before adopting rigid values that are derived from small groups. Lack of standard values for the 95th percentile may result in a premature delivery of an otherwise normal fetus. PMID- 1741872 TI - Uteroplacental Doppler flow velocity waveform analysis correlates poorly with glycemic control in diabetic pregnant women. AB - We examined 65 pregnant women with gestational (n = 31) and insulin dependent (n = 34) diabetes mellitus in order to evaluate the clinical usefulness of Doppler flow velocity waveform analysis in these pregnancies. Umbilical and uterine artery flow velocity waveforms were obtained during the third trimester with a continuous wave Doppler device. Quality of maternal glycemic control was evaluated by hemoglobin (Hb) A1 measurements at the time of delivery in 61 patients and by mean capillary blood sugars during the third trimester of pregnancy in four patients. There was no difference in various clinical and Doppler parameters between patients with good glycemic control and those with poor control. In contrast, the same clinical and Doppler parameters were significantly different in patients with preeclampsia than in those without preeclampsia, regardless of glycemic control. There was a poor positive linear correlation (r = 0.30, p less than 0.02) between maternal HbA1 and umbilical artery flow velocity waveforms (systolic/diastolic ratio). Proteinuria correlated better with umbilical artery systolic/diastolic ratio (r = 0.49, p less than 0.001). We conclude that Doppler flow velocity waveform analysis may be clinically useful only in diabetic pregnancies complicated by preeclampsia. PMID- 1741873 TI - Acute fatty liver of pregnancy associated with preeclampsia: management of hepatic failure with postpartum liver transplantation. AB - Acute fatty liver of pregnancy is a potentially fatal disorder. We report a patient complicated by preeclampsia, coagulopathy, encephalopathy, and hepatorenal syndrome successfully managed by postpartum hepatic transplantation. PMID- 1741874 TI - Impact of venous catheters on packed red blood cells. AB - This study was designed to test the hypothesis that there would be increased hemolysis, as indicated by an increase in plasma free hemoglobin and potassium, when packed cells were infused through small gauge percutaneous catheters (24 and 28 g, PC) compared with short catheters (24 g; SC). We were unable to study the 28 g PC because after 1 hour, at a flow rate of 10 ml/hr, only 2.4 ml packed cells were infused. There was a significant increase in plasma free hemoglobin when pre- and postinfusion values were compared (SC, p = 0.005; PC, p = 0.009), but a statistically significant increase in potassium only for the SC (p = 0.008). There were no significant differences between the catheters for either potassium or free hemoglobin. For either catheter the quantity of free hemoglobin transfused could potentially cause a significant rise in serum bilirubin and hemoglobinuria. PMID- 1741875 TI - Analgesia versus sedation during Broviac catheter placement. AB - Premature infants are capable of mounting physiologic and metabolic responses to pain. Systemic and local anesthesia reduce stress responses to major and minor surgical procedures. We evaluated the effects of local anesthesia (5 mg/kg lidocaine) preceded by either 1 mg/kg secobarbital (S) intravenously or by 2 micrograms/kg fentanyl (F) intravenously on the stress response to Broviac catheter placement. Twenty-nine premature infants ages 5 to 30 days, weighing between 650 and 1350 gm, were randomly assigned to either S or F groups. Age, birthweight, sex, race, and severity of illness were similar among S and F groups. Heart rate and blood pressure remained unchanged throughout the procedure. Oxygen saturation (O2sat) declined significantly in both groups during skin preparation and wound closure, but not during incision, dissection, or tunneling. In spite of fractional inspired oxygen adjustments made in 13 of 14 S- and 3 of 15 F-treated patients, decline in O2sat was more common and more pronounced (p less than 0.01) in S-treated babies. Hyperglycemic responses occurred in all S- and in none of the F-treated patients (p less than 0.001). Norepinephrine plasma concentrations did not change during Broviac catheter placement in either F or S group. Epinephrine concentrations were more elevated in S- than in F-treated patients, although these differences were not statistically significant. Low-dose fentanyl analgesia effectively complements local lidocaine anesthesia during Broviac catheter placement. Sedatives neither abolish metabolic responses to surgical stress nor prevent profound and persistent oxygen desaturation. PMID- 1741876 TI - Developmental follow-up of very low birthweight premature infants with low free thyroxine. AB - If a low level of free thyroxine (T4) is predictive of the true hypothyroidism in sick premature infants, long-term developmental follow-up of these infants should reveal a direct correlation between the free thyroxine level early in life and developmental disability in later years. Half of the 16 infants who were followed had normal free T4 (0.8 ng/dl or higher) and the remaining 8 infants had a low free T4 (0.38 +/- 0.15 ng/dl) during the first 2 weeks of life. Infants with low free T4 were followed sequentially during their stay in the neonatal intensive care unit and all eight showed free T4 levels more than 0.8 ng/dl by 36 to 44 weeks postconceptional age without any thyroid replacement. At follow-up, all 16 infants were functioning within normal range by Stanford-Binet testing at mean age of 4.6 years. There was no significant difference between the two groups in their motor development, hearing, language, or physical growth. Despite the small sample size, it appears there is no correlation between the free T4 levels during the first 2 weeks of life in infants 33 weeks' or less gestation and their developmental outcome at mean age of 4.6 years. PMID- 1741877 TI - Umbilical artery Doppler velocimetry: applications and limitations. PMID- 1741878 TI - [Heat radiation--an essential factor of heat transport in caloric vestibular tests? Current experimental findings]. AB - According to the accepted theory, in vestibular testing the caloric stimulus is transported from the auditory canal to the lateral semicircular canal by heat conduction via the bone. Some findings, however, are not consistent with this concept, e.g. the short latency of the vestibular response, and the fact that removing of the osseous bridge does not stop the transport of heat to the semicircular canal. Physically there are three modes of heat transport: conduction, convection, and radiation. So far, only the first two have been discussed with regard to vestibular calorization, however, they fail to explain the findings mentioned above. We carried out experiments on 10 cadaveric temporal bone specimens in order to evaluate the possible effect of heat radiation. With experimental conditions strictly regulated (specimens kept in climate box, 37 degrees C, saturated humidity, standardized irrigation of the auditory canal with 50 ml of water of 50 degrees C in 15 sec., temperature measured by thermistors at selected points of the specimen), the deviation in repeated experiments was within 0.1 degree C. In normal temporal bones a spreading of heat along the osseous structures was found in accordance with heat conduction via the bone. Then the bony bridge between posterior frame of the tympanic membrane and the lateral canal was removed along with the tegmen tympani, leaving the auditory canal and labyrinth connected only by a small anterior-inferior strut. The rise of temperature in the lateral canal, however, was not delayed and reduced, as expected, but faster and greater than in the original situation. If, now, a reflecting shield was inserted in the cleft between tympanic membrane and labyrinth the heat transfer was dramatically reduced. A similar effect could be achieved in the intact middle ear by a shield or by filling the cavity with gel. Convection as means of heat transport could be excluded. The experiments show that heat transport in the vestibular calorization is a complex process, which besides heat conduction involves radiation as an essential factor. This explains a number of experimental and clinical findings that, so far, had been unclear. PMID- 1741879 TI - [Equilibrium disorders and their diagnosis in childhood]. AB - Vertigo in children is rarer than in adults and the examiner in cases showing these symptoms must rely on the parents' or relatives' observations and details. Besides the equilibrium disorders caused by hereditary malabsorption or lesions in the peripheral or central vestibular structures, e.g. ototoxic drugs, tumours in the brain, meningitis, encephalitis, otitis, labyrinthine fistulas or head trauma, we only known of typical diseases, associated with vertigo, that develop during childhood. These are: so-called benign paroxysmal vertigo of childhood, benign paroxysmal torticollis, basilar migraine, spasmus nutans, visual-cliff phenomenon, and kinetosis. Careful examinations are necessary to differentiate these illnesses from vestibular epilepsy, brain tumours, and hereditary episodic vertigo. Neuro-otologic examination in children, especially small children, is a kind of "stepchild" in ENT departments. The reasons are the time-consuming examination necessary in the case of children and by problems connected with a plethora of troublesome individual tests. Additional difficulties arise in cases of sensory, mental, and other impairments. - The paper gives an overview of vestibular disturbances during childhood and diagnostic procedures for determination by means of Frenzel glasses, electronystagmography, cranio corpography, and posturography. PMID- 1741880 TI - [Masseter muscle flaps and buccal mucosa transposition flaps in the reconstruction of the dorsal oral cavity and the oropharynx]. AB - The m. masseter crossover flap according to Tiwari combined with a buccal mucosa transposition flap represents an excellent technique for a primary two-layered closure of defects due to surgical removal of T2- and small T3-tumors of the posterior part of the lateral floor of the mouth, the posterior edge of the tongue, the retromolar trigone, the soft palate and the tonsilar region. Especially advantageous are the low postoperative morbidity, the low rate of postoperative complications, and good functional and cosmetic results. The surgical expenditure is little and recommends the use of this technique also in patients with reduced operability. PMID- 1741881 TI - [Verrucous carcinoma of the oral mucosa]. AB - Verrucous carcinoma is a distinct variant of differentiated squamous cell carcinoma with low-grade malignancy, slow growth and no metastatic potential. Although it has been reported at extraoral sites, the tumor is mostly found in the oral mucosa. Clinically warty tumours with a grey-white, deeply cleaved surface are detected. The special feature of this tumour type is that it appears macroscopically malignant but histologically benign. The diagnosis of verrucous carcinoma may be difficult, since it is often lumped with verrucous hyperplasia or epidermoid carcinoma. In our study the clinical and histological characteristics of 32 cases of verrucous carcinoma of the oral cavity were investigated. The most common site was the mandibular buccal sulcus. The average age amount to 69 years. Adequate surgical excision is considered the treatment of choice. Because of the lack of metastatic spread a systematic treatment of the regional lymph nodes ist not mandatory. The prognosis of verrucous carcinoma is fairly good. PMID- 1741882 TI - [Assessment of the functional final condition following treatment of carcinoma of the oral cavity]. AB - The treatment of carcinoma of the oral cavity (tongue, floor of mouth, lips and palate) can lead to different degrees of mutilation. A simple and effective method of evaluation is described, that permits to determine the functional results of different treatments in individual patients. In a special evaluation form, the actual weight of the patient, continuing pain, activities at home and at work, xerostomia, visible mutilation, disorders of tongue mobility and sensitivity, speech impairment, swallowing disorders and psychological problems are assessed. The documentations is completed by application of a score system, that allows a reliable determination of functional results after treatment of oral cavity carcinoma. About 30 minutes are required to complete the investigation. 31 own patients were examined following transoral laser surgery for the treatment of oral cavity carcinoma. The results are demonstrated and compared to those following conventional surgery. PMID- 1741883 TI - [Regeneration of the ciliary beat of human ciliated cells]. AB - The influence of an isotonic, alkaline saline solution (diluted "Emser Sole" or brine from the spa of Bad Ems) on the ciliary beat of isolated cultured human ciliated cells of the upper respiratory tract was investigated. The ciliary beat was observed via an inverted phase contrast microscope (Zeiss Axiomat IDPC) and measured microphotometrically under physiological conditions and after the damaging influence of 1% propanal solution. Under physiological conditions the saline solution had a positive, although statistically not significant influence on the frequency of the ciliary beat. After damage of the cultivated cells by 1% propanal solution, the saline solution had a significant better influence on the regeneration of the cultured cells than a physiological sodium chloride solution. It is concluded that diluted brine from Bad Ems has a positive effect on the ciliary beat of the respiratory epithelium and accelerates its regeneration after damage by viral and bacterial infections, surgery or inhaled noxae. PMID- 1741884 TI - [Is it appropriate to consider wood preservative poisoning in the differential diagnosis of chronic recurrent respiratory tract infections?]. AB - Wood preservatives as pentachlorophenol and lindane containing the highly toxic compound dioxin were common to be used to protect woods inside the house. In a case report a couple of symptoms are shown as upper airway irritation with dry mucosa, headaches, sleeplessness, lack of concentration and psychosomatic problems caused by those wood preservatives. The typical sequence of the symptoms is given. The results of blood and urine analysis on pentachlorophenol and lindane lead to investigations on indoor materials, air and dust. Taking out the contaminated materials is the best and only treatment. PMID- 1741885 TI - [The value of indirect microlaryngo-stroboscopy in the follow-up care of patients with vocal cord carcinoma treated with primary irradiation]. AB - On the value of indirect Microlaryngo-stroboscopy in the follow-up of patients with vocal cord tumors having had primary radiotherapy: The technique of stroboscopy is explained, its weight in the evaluation of vocal cords vibration is discussed. Arrest of vibration may be a hint for a malignoma, particularly if this state develops again after radiotherapy. PMID- 1741886 TI - [Speech intelligibility and psychosocial adaptation in various voice rehabilitation methods following laryngectomy]. AB - Intelligibility and psychosocial adjustment are measured by the PLTT (Post Laryngectomy-Telephone-Test) and a newly developed questionnaire (FPAL). 110 male patients with total or partial laryngectomies are tested. Three different groups are compared with each other: laryngectomees with voice prostheses, laryngectomees with oesophageal voice or artificial larynx, and patients with partial laryngectomies. As was to be expected, intelligibility (single words and sentences) was best in patients with partial laryngectomies. The intelligibility of the laryngectomees with voice prostheses is significantly higher than the intelligibility of patients with oesophageal voice or artificial larynx. There was no difference between the groups with regard to the subjective assessment of intelligibility in relation to various communication partners. Partial laryngectomies have the lowest negative impact on the social and psychological situation of the patients. Laryngectomees, however, are more lonely, indicate more psychological stress in social interactions, and have a less positive evaluation of their life. Statistical analyses reveal no difference in psychosocial adjustment between laryngectomees with voice prostheses, oesophageal voice and artificial larynges. PMID- 1741887 TI - [Aberrant heterotopic salivary gland in a lateral neck cyst]. AB - An extra aberrant salivary gland located in a branchial cyst is presented. The branchial cysts are usually the result of a transformation disturbance of the branchial clefts and arches, or are cystic changes of the lymph nodes. The above finding can possibly be interpreted if we suppose that an aberrant salivary gland located in a lymph node can develop a cyst. The theory that branchial cysts originate from lymph nodes is encouraged by our case. This theory can also support the existence of unusual tumours in the neck, e.g. adenolymphomas. The content of these cysts can be easily approximately estimated via computed tomography. PMID- 1741888 TI - [The problem of deeply situated parotid tumors]. AB - Of 804 surgically treated parotid gland tumours, every fifth (19.9%) was situated medially from the 8th cranial nerve. Among these deep lobe tumours (DLT) there are more malignant tumours (36.8%) than in superficial lobe tumours (SLT; 11.4%). This fits especially the carcinoma arising in pleomorphic adenomas (14.3% in DLT; 3.1% in SLT). Postoperative complications of the 8th cranial nerve, defective tumour capsules, and necessary second or third look operations are more frequently in DLT than with SLT. Early diagnosis of tumours that are still small, is therefore very important. PMID- 1741890 TI - Theoretical models for traffic safety. PMID- 1741889 TI - [Training and technique of maxillary sinus sinoscopy]. PMID- 1741891 TI - Population and registered vehicle data vs. road deaths. AB - This paper discusses the use of rates to evaluate the effectiveness of countermeasures and to compare the safety of different countries and of different periods of time. The use of a rate requires an understanding of the shape of the curve relating the two variables. The use of the rates "death per registered vehicle" or "death per vehicle-kilometer" does not provide a consistent measure across time when there is a nonlinear relationship between number of deaths and number of vehicles. Predictive equations with one variable forming both part of the independent and dependent variable will suffer from spurious correlation. Smeed's equation does not predict the number of deaths in the original data set with any degree of overall accuracy, and cannot be assumed to predict accurately the number of deaths in other countries. The use of the number of persons killed rather than the number of fatal accidents might be questioned as one is the outcome of the other. More subdivisions of the total would be of more interest such as the numbers of different road user types within age groups. While deaths might be one of the common currencies of road injuries for comparing countries, there is little excuse for using them for examining trends within one country. Some performance measures that use the number of accidents and the number of persons (injured and uninjured) that are involved in them would be more meaningful than using deaths per vehicle. PMID- 1741892 TI - Forecasting road accident casualties in Great Britain. AB - There is considerable interest in many countries in the way in which their annual road accident casualty totals have developed. This leads inevitably to the question of how these totals are likely to change in the future. This paper assesses national data for Great Britain from 1949-1989 and forecasts the casualty total in the year 2000 by extrapolating the long-term decline in the rate of casualties per hundred million vehicle-kilometres. This forecast is conditional on the traffic growth predicted by that year, but it is found that uncertainty over the casualty forecast derives more from the slight irregularities in the past decline in the casualty rate than from uncertainty over the traffic prediction. Despite the use of a forecasting method that is based on an unusually strong time-series model, there is still real uncertainty about forecasting casualties over a gap of only 11 years. PMID- 1741893 TI - An aggregate accident model based on pooled, regional time-series data. AB - The determinants of personal injury road accidents and their severity are studied by means of generalized Poisson regression models estimated on the basis of combined cross-section/time-series data. Monthly data have been assembled for 18 Norwegian counties (every county but one), covering the period from January 1974 until December 1986. A rather wide range of potential explanatory factors are taken into account, including road use (exposure), weather, daylight, traffic density, road investment and maintenance expenditure, accident reporting routines, vehicle inspection, law enforcement, seat belt usage, proportion of inexperienced drivers, and alcohol sales. Separate probability models are estimated for the number of personal injury accidents, fatal accidents, injury victims, death victims, car occupants injured, and bicyclists and pedestrians injured. The fraction of personal injury accidents that are fatal is interpreted as an average severity measure and studied by means of a binomial logit model. PMID- 1741894 TI - A critical review of macro models for road accidents. AB - This paper presents a critical review of state-of-the-art macro models for road accidents. Such a review is meant to identify and establish the significance of policy and socioeconomic variables affecting the level of road accidents. The aim is to identify those variables associated with effective policies and interventions to enable decision makers to improve the level of road safety. The variables that appear to affect the number of fatalities or injuries are: vehicle miles travelled (VMT), vehicle population, income (in its various forms), percentage of young drivers, intervention policies such as speed limits, periodic vehicle inspection, and minimum alcohol-drinking age. Viewed critically, the state-of-the-art models being used to explain and predict road accidents are still deficient. One possible approach to correcting this deficiency draws from consumer utility theory, using analytical models built on a newly constructed theoretical framework. Success in estimating such models may improve predictions of road accidents, thus demonstrating the comparative cost effectiveness of alternative intervention policies. PMID- 1741895 TI - The development of traffic and traffic safety in six developed countries. AB - Two models are presented, describing the development of traffic and traffic safety. Traffic volumes, measured by the total amount of vehicle kilometers per year, are expected to follow a sigmoid saturation curve over time. The logistic function is used to model this development. The fatality rate, the number of fatalities per vehicle kilometer, is chosen to measure safety. The (negative) exponential function is selected to model the fatality rates over time. It is argued that these two aspects of the traffic system are fundamental and that the development of the number of fatalities results by multiplication. Given this assumption, the fall in the number of fatalities, noticed in almost all developed countries after a steady increase until 1970, does not need a special explanation. It follows from the combination of the monotonically increasing traffic volumes and the monotonically decreasing fatality rates. The two parsimonious models fit the data fairly well for six developed countries. The parameters differ substantially between countries, but also show common features. It is found from the parameters of the logistic function, that for all countries the points of maximum increase in traffic volume coincide just after 1970, the moment of the energy crisis. It is concluded from this finding that the energy crisis was caused by the cumulating demands of the oil-consuming countries, resulting in a reaction of the oil-producing countries. From the parameters of the exponential function, it is found that there also is a common point of intersection for fatality rates around 1980. It is shown that the development of safety is directly related to the development of traffic. The ten-year delay is interpreted as the time necessary for planning and implementation of safety measures. Finally, a striking relation is found between the volume parameters and the fatality-rate parameters, suggesting that the number of fatalities is a function of the derivative of the amount of traffic in the mathematical sense. PMID- 1741896 TI - Development of traffic and traffic safety: global trends and incidental fluctuations. AB - In this, and previous related papers, developments of traffic volumes and traffic safety are studied from a system-theoretic point of view. It was proved already that such an approach is effective and leads to new and interesting theoretical facts. Models for the description of long-term developments of traffic volumes and safety were established, and particular relations between both developments were found. One of these findings was, that the number of fatalities turned out to be a function of the derivative of the logistic function describing the development of the number of vehicle kilometres over the years. It was noted that the model deviations for the number of fatalities and the vehicle kilometres were not merely random, but also had systematic components. In the present paper these deviations were further investigated. For the Netherlands, it is clearly shown that the number of fatalities is a function of the derivative of the number of vehicle kilometres, but with a shift in time. The short-term deviations from this long-term development are also related to the derivative of the number of vehicle kilometres, but without a shift in time. For five other countries similar relations were found, although the description of the short-term fluctuations seems to be a bit more complicated. In general, it can be concluded that the system-theoretic approach turned out to be highly effective for the description of long-term and short-term developments in traffic volumes and safety. For the Netherlands up to 95% of the variance in fatalities can be "explained" by developments in traffic volumes alone. It is clearly demonstrated that, although it will be very difficult to single out effects of specific safety measures, the combined safety actions taken by a society are very effective in getting the safety factor under control. The most valuable fact that can be learned from this analysis is that, if increased developments in traffic volume occur or are predicted, the immediate safety effects can also be estimated. Therefore, anticipatory safety measures can be taken to cope with these effects before (or immediately after) the moment they appear, improving safety management at a more rational and preventive basis. PMID- 1741897 TI - Simple models of fatality trends revisited seven years later. AB - The author's original paper presented simple linear models of fatalities based on data through 1982 and appeared in this journal in 1984. The earlier paper reported good fits through 22 years of fatality counts using population and employment data, after adjusting for the short-term effect of the oil shortage (in 1974) and the long-term effect of the 55 mph speed limit (beginning in 1974). Attempts (reported here) to refit the model through seven additional years were less successful. It may be that the relationships originally reported have changed, that important new factors have been introduced, or that the original fits were partly luck. The recent emphasis on behavioral solutions to safety problems (including programs to decrease alcohol use and increase safety belt use) is one important change, so the effect of the benefits of these programs on the model fits is explored. The original model began to overpredict fatalities just as safety benefits were beginning to accrue from increased safety belt use and decreased driver-alcohol involvement, and both the model overprediction and the benefits of these programs increased over the seven years of data added to the original model. Thus, previous government estimates of the number of lives saved by these behavioral programs are supported by the observed change in the statistical relationship between fatality counts and economic factors. PMID- 1741898 TI - Determinants of motor vehicle deaths in the United States: a cross-sectional analysis. AB - This paper uses 1987 state-level data and least-squares regression to estimate a model of motor vehicle deaths in the United States. The model includes several factors accounted for in previous cross-sectional studies of these fatalities. The estimates suggest that income, the ratio of urban to rural driving, expenditures on highway police and safety, motor vehicle inspection laws, and adult seat belt use laws with secondary enforcement provisions are inversely related to motor vehicle death rates. They also indicate that volume of driving, speed, speed variance, driving density, alcohol consumption, temperature, and a dummy variable for western states are directly related to the rates. PMID- 1741899 TI - Are traffic deaths in Ireland related to alcohol consumption? Restudying a time series model. AB - The traffic death rate and per capita alcohol consumption in Ireland were found by Walsh to be correlated. However, a more detailed analysis shows that changes in traffic deaths precede changes in alcohol consumption. Therefore, the correlation can not reflect a causal relation. When a speculative variable is included, the relation becomes concurrent. The overall conclusion is that there is no credible evidence for a relation between per capita alcohol consumption and traffic deaths. PMID- 1741900 TI - The effect of airline deregulation on automobile fatalities. AB - This paper attempts to quantify the effects of airline deregulation in the United States on intercity automobile travel and consequently on the number of highway fatalities. A demand model is constructed for auto travel, which includes variables representing the price and availability of air service. A reduced form model of the airline market is then estimated. Finding that deregulation has decreased airfares and increased flights, it is estimated that auto travel has been reduced by 2.2% per year on average. Given assumptions on the characteristics of drivers switching modes and the types of roads they drove on, the number of automobile fatalities averted since 1978 is estimated to be in the range 200-300 per year. PMID- 1741901 TI - The economy as a factor in motor vehicle fatalities, suicides, and homicides. AB - The effect of the economy as reflected by employment and unemployment rates on motor vehicle fatalities, suicides, and homicides is examined using several national databases. First, regression models are fit to these fatality data overall as well as for a variety of age-race-gender subgroups. Then time series models-autoregressive integrated moving average (ARIMA) and structural time series analysis-were fit to the data, both with and without the economic indicators, to examine the relative ability of the models to forecast subsequent fatalities. No evidence was found using any of the modeling techniques that knowledge of yearly values of rates of employment, unemployment, and nonlabor force leads to improved forecasts of the level of motor vehicle fatalities, suicides, or homicides in the total U.S. population or within various subpopulations of interest. PMID- 1741902 TI - [Intravenous application of calcitonin following unsuccessful thermocoagulation of the dorsal root entry zone]. AB - Following a traumatic lesion of the brachial plexus, severe pain syndrome in the left shoulder and arm developed in a 42-year-old patient. The pain could not be relieved by multiple therapeutic attempts. Therefore, electrocoagulation of the substantia gelatinosa was performed on the affected side of the evulsed plexus from the dorsal aspect of the cervical spinal cord (Dorsal-Root-Entry-Zone Lesion, DREZ-operation). After temporary relief, the initial pain syndrome returned. Intravenous salmon-calcitonin infusions administered at our pain clinic led to almost complete remission of pain. Six months later the original symptoms returned and therefore the same infusion scheme was repeated with identical results. PMID- 1741903 TI - [Preoperative donation of autologous blood and plasma]. AB - The risk and side effects of homologous blood transfusion led to an increased interest in autologous transfusion concepts. Whereas peri- and intraoperative procedures are clinical methods, preoperative autologous blood donation belongs into the responsibility of a transfusion service in order to ensure qualified separation into blood components as well as correct storage and handling. Special knowledge in transfusion medicine is necessary for the application of preoperative autologous plasmapheresis. On the other hand, its use by clinicians under adequate controlled conditions seems to be rather safe. Although autologous transfusion includes the lowest risk, side reactions cannot be completely excluded. There is also a risk of secondary bacterial contamination. Side effects due to the specific composition of the various blood components, to alterations during storage and to the way of application have to be considered, too. Severe haemolytic transfusion reactions are mostly caused by exchange of blood samples, patients or blood units. They are to be expected in autologous blood transfusion as well. In addition, there is an increased risk of infection when autologous blood components are exchanged accidentally. There is only an indication for autologous blood if the total risk of autologous donation as well as transfusion in the individual case is lower than the statistical risk of homologous transfusion. Autologous blood donation should be offered to all patients undergoing elective surgery where blood is likely to be required and when blood donation is practicable. Preoperative autologous plasmapheresis is indicated in elective surgery if intra- and perioperative autotransfusion methods shall be used and a blood loss of at least 1.5 liters can be expected. There are a lot of organizational problems in autologous blood transfusion which can be solved by adequate information of all persons involved and close cooperation between clinicians and transfusion service. The high standard which was developed for homologous transfusion in the last 15 years has to be maintained for autologous blood transfusion, too. PMID- 1741904 TI - [Autologous blood use in patients with rheumatic diseases]. AB - A four-step autotransfusion concept consisting of preoperative autologous blood predeposit, isovolaemic haemodilution, preoperative plasmapheresis and intraoperative autotransfusion in rheumatic patients undergoing major planned operations associated with considerable blood loss is presented. The autotransfusion concept was established in 1988. At that time 47% of the total blood demand was replaced by autologous transfusions. In 1989 there was an increase to 88% and in 1990 even to 94%. It is pointed out that under normovolaemic conditions the chronic anaemia of these rheumatic patients is neither a contraindication for preoperative autologous blood predeposit nor for intraoperative autotransfusion. PMID- 1741905 TI - [A new method of non-invasive determination of the cardiac minute volume in ventilated patients]. AB - A method for the determination of stroke volume and cardiac output from pulse synchronized variations of pressure in mechanically ventilated patients is described. A comparison with 20 readings obtained by thermodilution showed good correlation (r = 0.9866). PMID- 1741906 TI - Propofol safely used in a neuroleptic malignant syndrome patient. AB - Anaesthetic regimens for patients with the poorly understood neuroleptic malignant syndrome (NMS) are not well outlined. In this case report, NMS and its questionable relation to malignant hyperpyrexia are outlined. Satisfactory use of total intravenous anaesthesia, based on propofol, in an NMS-susceptible patient is presented. PMID- 1741907 TI - [Perforation of the palate following prolonged orotracheal intubation--a case report]. AB - A report is given on a patient, who showed a perforation of the palate after prolonged orotracheal intubation. Etiology as well as prophylactic measures with a tracheostomy in good time for avoiding such complications are discussed. PMID- 1741908 TI - [The liability of employed physicians in the "New German States" in 1991]. AB - The law has essentially changed in the "New German States" (in former times "East Germany") since the unification of East- and West-Germany on the 3rd of October 1990. The civil code ("Burgerliches Gesetzbuch = BGB") is now valid for all working conditions. But due to the "Unification Treaty" the regulations regarding the hospital liability ("Materielle Verantwortlichkeit der Gesundheitseinrichtung = mVGe") are still existing until the 31st of December 1991. Now, however, it is possible that in case of malpractice the patient may claim the employed physician directly liable. PMID- 1741909 TI - A new insight into the mycobacterial cell envelope architecture by the localization of antigens in ultrathin sections. AB - In an attempt to have a better insight into the mycobacterial cell envelope architecture, various subcellular fractions of Mycobacterium avium were prepared and characterized chemically and ultrastructurally. The various fractions corresponding to the mycobacterial "capsular material", outer layer, cell wall skeleton, cytoplasmic membrane, and cytosol as well as intact bacteria were then used to raise antisera in rabbits. The antisera so raised were then used to immunolabel the intact bacteria prior to embedding in epon. In parallel studies, bacteria were processed by a novel gelatin-uranyl acetate-low temperature Lowicryl HM20 embedding which preserved mycobacterial antigens, permitting to immunolabel antigens on ultrathin sections. Immunolabelling of epon-embedded intact bacteria showed that in the tripartite structure of the bacterial cell envelope, the middle electron-transparent layer acted as a barrier, not permitting the antibodies to penetrate into deeper structures. Immunolabelling of ultrathin sections showed that mycobacteria were surrounded by a "capsule" containing specific surface antigens with a glycocalyx-like topography, and that the intermediate electron transparent layer which separated the surface amphiphils from the inner arabinogalactan-peptidoglycan layer, was a virtual no man's land as it only seldom contained a single gold particle irrespective of the various antisera used. Furthermore, location of various layers in the cell envelope of M. avium using antisera raised against the subcellular fractions prepared was in agreement with chemical and ultrastructural data. A cell envelope model compatible with chemical, ultrastructural and immunolabelling data is proposed and its validity discussed. PMID- 1741910 TI - Coagglutination test for rapid detection of Salmonella enterotoxin. AB - The Staphylococcal Coagglutination (CoA) test using Staphylococcus aureus (Cowan type-1) cells coated with antiserum against purified Salmonella enterotoxin was standardized and carried out to screen Salmonella serotypes for their enterotoxigenicity. Of the 101 cell-free culture supernatants from an equal number of Salmonella strains belonging to 15 different serotypes tested, 76 were found to be enterotoxigenic. All of the 24 strains which gave positive reactions in the rabbit ligated ileal loop test were also positive with this test. As little as 7.5 ng of purified Salmonella enterotoxin could be detected by the CoA test. The presence of enterotoxin in polymyxin B extract of cells and cell-free preparation of a S. typhimurium strain was detected as early as after 1.5 and 3.0 h of incubation, respectively. Besides the test standardized with the antiserum to purified V. cholerae toxin (CT) could detect purified toxin in a quantity as little as 5.0 ng and also enterotoxigenicity in an E. coli strain (LT+). The usefulness of the test as a routine, rapid and economic one for the detection of enterotoxin of Salmonella, Vibrio cholerae and E. coli is discussed. PMID- 1741911 TI - Sequential culturing method improves recovery of Legionella spp. from contaminated environmental samples. AB - Investigations were undertaken to improve detection and isolation of Legionella spp. from samples containing a large number of non-legionellae isolates. The direct fluorescent antibody staining technique was used in conjunction with a sequential culturing method which was developed to improve the recovery rate of Legionella spp. from such samples. The technique for enrichment and isolation of Legionella spp. from environmental samples includes storage at 4 degrees C and repeated culture on freshly prepared media. Heat and acid treatments were included when deemed appropriate. A DNA probe was used for confirmation of Legionella. Treatment of the water samples, as described, and co-cultivation with amoebae naturally present in the samples are concluded to be responsible for increased success in recovery of Legionella isolates. PMID- 1741912 TI - Removal of the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine by BACTEC resin-containing blood culture medium. AB - We determined the capacity of BACTEC resin blood culture media NR 16A and NR 17A to remove the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine. Simulated blood cultures containing increasing antibiotic concentrations were inoculated with 10(1), 10(3) and 10(5) CFU/ml blood of various bacterial strains and evaluated with the BACTEC infrared growth detection system. The antibiotic concentrations were adjusted to give breakpoint concentration in the added serum volume or in the total volume of the blood culture vials. Recovery rates and time until detection of bacterial growth in resin-media were compared with those in resin-free media. Trimethoprim sulfamethoxazole and ofloxacin were, similar to piperacillin, inactivated by resins at antibiotic concentrations that were up to ten times higher than those easily achievable in serum. The antimicrobial effect of zidovudine on gram negative bacteria was reduced in resin media at concentrations corresponding to fifteen times the peak serum levels. Growth of P. aeruginosa, but not of S. aureus, E. coli, K. pneumoniae and Salmonella, was delayed in the presence of resins even at subinhibitory antibiotic concentrations when compared with resin free media. PMID- 1741913 TI - Isolation and characterization of group B streptococcal type antigens X and R. AB - The group B streptococcal surface antigens X and R were isolated from culture supernatant by ammonium sulphate precipitation and subsequent high performance gel filtration (HPLC). The type antigens appeared in numerous protein bands. Type antigen X was in the range of 180 kD, type antigen R, in the range of 116 kD. The protein antigens reacted specifically with their homologous antisera in Western blot analysis and in immunoelectrophoresis, indicating that there was no immunological relationship between both proteins. Preparative isoelectric focusing of the X and R antigens revealed for both proteins isoelectric points at acid pH. Specific antibodies produced against the purified proteins could be used for routine serotyping without further absorption. PMID- 1741914 TI - Use of the enzyme linked immunosorbent assay (ELISA) to detect the IgM and IgG antibody response to Leptospira interrogans Serovar hardjo in pregnant ewes. AB - Fourteen pregnant ewes were inoculated with Leptospira interrogans serovar hardjo via intramuscular injection or inoculation via the conjunctiva. The serological response to inoculation detected by the microscopic agglutination test was compared to IgM and IgG antibody levels detected by enzyme linked immunosorbent assay. Intramuscular injection produced a better serological response than conjunctival inoculation. The mean IgM response was short lived whereas the IgG antibody response and the MAT persisted for much longer. The IgM antibody levels may be useful as an indicator of recent exposure. Although leptospiruria was not established in any of the animals, 6 of the 14 pregnant ewes failed to rear a healthy lamb. PMID- 1741915 TI - Erythrina lectins detect the H/HI blood groups. AB - The lectin purified from Erythrina corallodendron seeds which binds N acetyllactosamine greater than N-acetyl-D-galactosamine greater than alpha and beta galactosides greater than D-galactose was examined for its ABO(H) blood group specificity. It has been shown that this lectin causes the strongest hemagglutination of O(H) and weakest of Oh(Bombay) red blood cells, and interacts with the H antigen in association with the I antigen. The reactions of Erythrina corallodendron and Erythrina indica lectins (which are similar in sugar specificity) with erythrocytes of different ABO(H) and Ii blood groups (the I bloods were all from adults and the i from either cord or adult bloods) revealed the following order of activity: O(H)I greater than A2 I greater than O(H)i adult greater than A2BI greater than BI greater than O(H)i cord greater than A1I greater than A1i adult greater than Bi cord greater than A1BI greater than Ai cord greater than ABi cord greater than OhI. The Erythrina indica lectin showed a lower differentiation between the agglutination of O(H) and Oh erythrocytes. Both Erythrina lectins exhibited H/HI blood group preference but were not inhibited by the saliva from ABO(H) "secretors". Thus they may be classified with the Cytisus sessilifolius, Lotus tetragonolobus and Laburnum alpinum lectins which are inhibited by lactose but not by H blood group substances in secretions. PMID- 1741916 TI - Use of the SL-IV and the PGL-Tb1 glycolipid antigens in ELISA for the diagnosis of tuberculosis in AIDS patients. AB - At a predetermined specificity of 100.0%, the sensitivity of ELISA using the PGL Tb1 and SL-IV antigens and IgG assays was 35.0% for the diagnosis of tuberculosis in AIDS patients (44.1% when tuberculosis was diagnosed before AIDS, 21.7% when AIDS was diagnosed before tuberculosis). Serial assays in sera collected from 11 AIDS patients before tuberculosis was diagnosed indicated that significant antibody titres were detected 10 months before the onset of clinical tuberculosis. Consequently, it was proposed that serodiagnosis using the glycolipid specific antigens should help in deciding on preventive antituberculosis treatment in these patients. PMID- 1741917 TI - Adhesion of Staphylococcus saprophyticus to renal tubular epithelial cells is mediated by an N-acetyl-galactosamine-specific structure. AB - S. saprophyticus CCM883 and 9325 were found to adhere to the tubular cell line LLC-PK1. An ELISA technique was used to determine adherence of bacteria and inhibition of adherence by various carbohydrates. Only N-acetyl-galactosamine was found to significantly inhibit adhesion (p less than 0.001), which suggests that the surface component mediating adhesion recognizes structures on the target cell that contain this carbohydrate. PMID- 1741918 TI - Chemotherapy in the treatment of periodontopathy. AB - We treated 27 patients suffering from periodontitis with 750 mg/d oxytetracycline over a fortnight and compared them with a control group of 25 patients who received only a placebo. The selection of patients followed certain criteria. For controlling of the success of treatment, we developed a simple model of clinical and microscopical parameters. A significant difference between both groups could be demonstrated six months after starting the treatment. PMID- 1741919 TI - Molecular cloning and nucleotide sequence of a new plasmid-coded Klebsiella pneumoniae beta-lactamase gene (SHV-2a) responsible for high-level cefotaxime resistance. AB - Patient specimen isolates of Klebsiella pneumoniae exhibiting an MIC of greater than 128 mg/l for cefotaxime were shown to produce a beta-lactamase with a pI of 7.6, which is encoded on a 66 kb conjugative plasmid. A 3.5 kb Bam HI fragment of this plasmid was cloned into pLG339 and totally sequenced. The nucleotide sequence of the beta-lactamase gene presented 99% homology to those of SHV-2 and SHV-3, the deduced amino acid sequence differed from both enzymes in one and two positions, respectively, leading to the denomination SHV-2a for the new enzyme. Since the kinetic data of SHV-2a and SHV-2 are similar, too, quantitative effects mediated by distinctly different promotor regions are thought to be responsible for the elevated MIC for cefotaxime induced by SHV-2a. PMID- 1741920 TI - Activation of mononuclear immune cells in response to staphylococcal lipoteichoic acid. AB - The goal of the present study was to evaluate the influence of staphylococcal lipoteichoic acid (LTA) on the activation of mononuclear immune cells. A murine tumor necrosis-like factor (TNF-like) was induced in the sera of CD-1 mice which had been primed with heat/formalin-inactivated Propionibacterium avidum KP-40 and subsequently exposed to LTA extracted from Staphylococcus saprophyticus strain S 1. Monoclonal antibody against murine TNF (anti-TNF) significantly inhibited the cytostatic activity of mice sera against transformed L-929 cells. Freshly isolated lymphocytes did not display interleukin 2 (Il-2) receptors, but receptors were expressed on Con A incubated cells and in significantly higher numbers after coexposure to staphylococcal LTA in vitro. Since the induction of TNF (macrophages) and Il-2 receptors (lymphocytes) represent stimulation of the mononuclear immune system, staphylococcal LTA may be considered to be an immunomodifier. PMID- 1741921 TI - A Lyme borreliosis human serosurvey of asymptomatic adults in Ireland. AB - Blood samples were obtained through the Blood Transfusion Service in Ireland in order to obtain information on the prevalence of asymptomatic B. burgdorferi infections and in an attempt to identify the type of habitat that presents the most risk of infection. Areas in the country were rated as low, medium or high risk based on the availability of suitable tick habitat, access to the public and the distribution of deer, the latter parameter being related to both the occurrence of rodent reservoir hosts and woodland recreational areas. Approximately 100 plasma samples from each of four areas were analysed for IgG anti-Borrelia antibodies by indirect immuno-fluorescence with a titre of 1 :80 indicating a positive reaction in asymptomatic individuals. Prevalence figures of 15, 11, 8 and 5% were obtained for high, high/medium, medium/low and low risk areas respectively. No positive samples were detected in blood from an Icelandic population which is not exposed to I. ricinus bites. The overall subclinical prevalence (9.75%) is surprisingly high in view of the apparent rarity of clinical cases in Ireland, though under-diagnosis probably occurs. These results seem to indicate that farmland is less important than woodland as Lyme borreliosis habitat. If this is so, it is probably due to the presence in woodland of Apodemus sylvaticus, a putative reservoir host, and also to the use of such areas for recreation at certain times of the year. PMID- 1741922 TI - The discovery of creatinine assimilation in Cryptococcus neoformans, and subsequent work on the characterization of the two varieties of C. neoformans. AB - The discovery of creatinine assimilation in C. neoformans by Staib served as the foundation for our biochemical, genetical, ecological, epidemiological and taxonomic studies on the two varieties of C. neoformans for the past 15 years. The two varietal concept is now widely accepted and the arrival of AIDS epidemic has promoted the recognition of the differences between the two varieties, especially in their epidemiology and ecology. Since the agent of cryptococcosis in AIDS patients almost always belongs to the var. neoformans even in geographical areas prevalent for var. gattii, it is important to study the possible differences in the pathogenesis of the two varieties. PMID- 1741923 TI - Peritonitis caused by Trichomonas--a preliminary case report. AB - Trichomonas infections of the abdominal cavity are uncommon and case histories have not been published previously. A patient to whom reference is made this paper developed a combined immunodeficiency syndrome and portal hypertension with ascites on the basis of a cirrhosis of the liver. This seems to have been the precondition for a peritonitis caused by a Trichomonas species. PMID- 1741924 TI - In vitro damaging effect of leukocytes, serum, and peritoneal fluid on Ascaris suum infective larvae. AB - Peritoneal leukocytes, serum, and peritoneal fluid from Ascaris suum-infected or noninfected mice were studied using 51Cr release and larval mobility to determine if they had in vitro cytotoxicity for A. suum infective larvae. Mouse serum or peritoneal fluid from infected and non-infected mice was added to leukocyte larvae cultures to determine their effect on leukocyte damage to larvae. Leukocytes from A. suum infected mice were cytotoxic for A. suum larvae in the presence of serum from infected or noninfected mice but only serum from infected mice produced larval cytotoxicity independent of leukocytes or in the presence of leukocytes from noninfected mice. Mouse peritoneal fluid from infected or noninfected mice was found to damage larvae independent of leucocytes. Cytotoxic activity was blocked when serum or peritoneal fluid was heat-inactivated suggesting complement as the damaging agent. PMID- 1741925 TI - Leptospires isolated from toads and frogs on the Island of Barbados. AB - Four pathogenic strains of leptospires were isolated from the kidneys of toads (Bufo marinus) and seven from frogs (Eleutherodactylus johnstonei). Isolates from two toads and one frog belonged to serovar bim, the causative agent of most cases of severe leptospirosis on Barbados. The other eight strains belonged to a new serovar within the Australis serogroup. The name bajan is proposed for this new serovar of Leptospira interrogans. PMID- 1741926 TI - WHO in Europe 1991. PMID- 1741927 TI - Extrinsic asthma and environmental allergens. AB - House dust mites allergens are one of the most common antigens able to induce a high degree of sensitization in a general population. Owing to the possibility of quantifying the amount of major mite allergens in the environment, epidemiological studies have led to propose threshold values above which there is an increased risk for the occurrence of mite sensitizing, for the development of asthma and for the occurrence of symptoms. All these studies and some others dealing with the number of mites in house dust support the hypothesis that exposure to house dust mites may have a major influence on developing allergic diseases. PMID- 1741928 TI - Intrinsic asthma: myth or reality? AB - Asthma is a multifactorial syndrome with different etiologies, both allergic and non-allergic. Response to an allergen may be moderate and may often be shown only by provocation tests, not by skin tests or RAST. Food allergy is a significant cause of asthma. There are many non-allergic causes, from gastro-oesophageal reflux to aspirin-intolerant asthma, to sulphites...the list is far from exhaustive. Often there is an association of allergic and non-allergic causes. PMID- 1741929 TI - [Treatment of asthma in the adult using a combination of salbutamol 100 micrograms--beclomethasone 50 micrograms. Results of a study on 1917 patients seen in general medicine]. AB - Efficacy and safety of salbutamol--beclomethasone combination were studied in a multicentre trial in general practice which included 1917 asthmatic patients. During a 7 day run-in period, the number of dyspnea episodes, the morning and evening PEFR values were recorded daily. Patients were then treated with 2 puffs of salbutamol--beclomethasone combination t.i.d. or q.i.d. Results showed a significant improvement of the daily number dyspnea episodes (from 2.7 to 1.4) and of the daily number of salbutamol puffs used as rescue medication (from 5,1 to 2,5) (p less than 0.001). Morning and evening PEFR were increased by 50 litres min-1 (p less than 0.001). Symptoms were significantly improved, particularly nocturnal dyspnea (p less than 0.001). Minor and usual adverse events were noted in only 2,7% of the population. Salbutamol--beclomethasone allows a good control of asthma, particularly a good nocturnal cover. This efficacy with a good safety profile makes salbutamol--beclomethasone combination a well-adapted maintenance treatment of asthma. PMID- 1741930 TI - Asthma and HLA system. AB - Study of atopic asthma provides an excellent model for our understanding of the complex molecular genetics of human immune responsiveness. Family and population studies have suggested that multiple genetic factors influence global and specific immune responsiveness to allergens. Global response of IgE production appears to be controlled by a dominant "atopy gene" unlinked to HLA class II associated Ir genes, whereas the specific immune response in terms of IgE and IgG antibodies against precise allergens is unequivocally linked to the HLA class II molecules. Other genetic factors/polygenic component may influence the bronchial hyperreactivity observed among asthmatics. Not the least, the genetics of the "releasability" of mediators of inflammation from basophils should also be considered in the genetic studies of asthma. Given this overall complexity of genetics of asthma, we primarily focused our attention to the genetics of a defined subgroup of asthmatic patients. We have chosen to study three well defined clinical subsets (atopic asthma with and without aspirin sensitization, and nonatopic asthma with aspirin sensitization) in comparison to age and sex matched control groups for their HLA class II polymorphism at the DNA level. Use of in vitro DNA amplification and allele specific restriction enzymes allowed us to define that a particular combination of a specific DQ and DPB alleles is highly prevalent among asthmatic patients with aspirin sensitization and this is exclusively in an atopic context (R.R. = 54). Intriguingly, an identical combination of HLA alleles are similarly enriched among patients with coeliac disease. Further studies are required to understand such an intriguing similarities of molecular markers between these apparently two unrelated disorders. PMID- 1741931 TI - Ubiquitous expression of TNF-alpha/cachectin immunoreactivity in human endometrium. AB - Emerging evidence suggests that cytokines play significant roles as intercellular communication signals in human endometrium. In the present report, an immunohistochemical staining method and tumor necrosis factor-alpha (TNF-alpha) specific polyclonal antibody was used to identify potential in vivo sources of this cytokine in human endometrium. During the proliferative and early secretory phases of the menstrual cycle, glandular epithelium was distinctly free of any immunoreactive product. With the emergence of mid- and particularly late secretory phases, however, some glandular epithelial cells started to express TNF alpha. In the late secretory phase, glands exhibiting strong staining were adjacent to those that were negative for TNF-alpha or only sparingly contained positively immunostained cells. Remarkably, the glandular epithelium constituted a major source of enhanced expression of TNF-alpha during gestation. In the proliferative phase, virtually all stromal cells strongly expressed TNF-alpha, and in the secretory phase, some variability of staining could be observed among various stromal cells. In gestational endometria, decidual cells and in all endometria, endothelial cells strongly expressed immunoreactivity for TNF-alpha. These data demonstrate that various constituents of endometria are constitutively primed to express TNF-alpha and that this expression is distinctly associated with the changes in endometrium that are compelled by hormonal stimuli. PMID- 1741932 TI - Screening assays for immunologic infertility: a comparison study. AB - Because the immunobead antisperm antibody test (IBT) is difficult to learn and results are heavily operator-dependent, we compared findings on IBT with those of SpermMAR and SpermCheck in 58 patients to determine whether the latter two tests could demonstrate improved screening ability. Assays performed on both sperm and serum (i.e., direct and indirect) yielded 100% positive predictive values when IBT was used as the standard. Both SpermCheck and SpermMAR are easier to perform, and, as the former has a slightly greater sensitivity, we recommend SpermCheck for the detection of immunologic infertility. PMID- 1741933 TI - Familial recurrent spontaneous abortions. PMID- 1741934 TI - Type I conceptus interferons: maternal recognition of pregnancy signals and potential therapeutic agents. AB - In summary, Type I conceptus interferons of sheep, cows, and goats (perhaps all ruminants), which signal maternal recognition of pregnancy, may be useful for enhancing fertility in animal agriculture and may have a role in human and veterinary medicine as well. The Type I conceptus interferons share antiviral, anticellular, and immunosuppressive properties with Type I leukocyte interferons, but lack their cytotoxic effects, which may make them especially useful as therapeutic agents in human and veterinary medicine. The unique N-terminal structure of oTP-1 may account for its distinctive biological properties, including its antiluteolytic activity. PMID- 1741935 TI - Epidemiology of recurrent spontaneous abortion. AB - With recent scientific advances leading to better understanding of the immunobiology of recurrent spontaneous abortion (RSA), interest has now focused upon the epidemiology of RSA. A cohort of 214 couples with a history of two or more consecutive abortions were studied for the prevalence of etiologic factors and association with other reproductive failures. The prevalence of causes of RSA in this cohort was compared with etiologic factors among 179 couples with a history of three or more consecutive abortions. The obstetrical histories of 214 women with RSA were analyzed for the total number of pregnancies, live births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. These numbers were compared with the expected frequency of each in the general population. The prevalence of etiologies among 214 with RSA were as follows: chromosomal-6%, anatomic-1%, hormonal-5%, immunologic-65%, and unexplained-23%. No differences in the prevalence of etiologic factors exist when couples with a history of two or more abortions are compared with three or more abortions. When the number of ectopic pregnancies, molar pregnancies, and stillbirths among 214 women with RSA were compared with the expected numbers, the odds ratios were 2.2 for ectopic pregnancies, 6.0 for molar pregnancies, and 2.3 for stillbirths. These data indicate that no difference in the prevalence of etiologies of RSA exist when couples with two or more abortions are compared with three or more and a comorbidity between RSA and other types of reproductive failure exists. PMID- 1741936 TI - Antinuclear autoantibodies in healthy nonpregnant and pregnant women and their offspring. AB - Antinuclear autoantibodies have previously been detected in sera of healthy women although less frequently than in sera of women with autoimmune disorders. The effect of pregnancy on antinuclear autoantibody production in healthy women is as yet debatable. We present four studies in which, by employing the ELISA method, we evaluated the presence of six antinuclear autoantibodies (anti-ds DNA, anti-ss DNA, anti-poly(I), anti-cardiolipin, anti-Sm, and anti-RNP) in the sera of more than 1,000 healthy pregnant and nonpregnant women, including 196 pairs of matched maternal and cord blood sera. In all four studies healthy pregnant women did not demonstrate significantly higher prevalence rates of various serum antinuclear autoantibodies as compared to healthy non-pregnant women. All detected autoantibodies were of the IgM isotype. In only one infant (born to a healthy seronegative mother) was an autoantibody (IgM anti-ss DNA) detected. This may indicate that in certain circumstances the fetus is capable of self-production of autoantibodies. PMID- 1741937 TI - Autoantibodies and pregnancy wastage. AB - The established association between a relatively specific group of autoantibodies binding negatively charged phospholipids and poor pregnancy outcome has advanced treatment options for women with this diagnosis. Evidence for an association between systemic autoimmune disorders and otherwise unexplained obstetric complications, in the absence of a documented antiphospholipid antibody(s), is reviewed. The existence of autoantibodies with other specificities that could be related to fetal wastage has been suggested by associations between poor obstetric histories and nonspecific serologic abnormalities observed in women with no clinical signs of an autoimmune disorder. Because signs and symptoms of vasospasm such as Raynaud's phenomenon or placental infarction have been observed in women with a history of unexplained fetal demise, a search for autoantibodies recognizing antigens common to trophoblastic and vascular cell surfaces is suggested. PMID- 1741938 TI - Mouse model for the treatment of immune pregnancy loss. AB - Spontaneous abortions can be associated with preimplantation embryo loss, implantation problems and a variety of postimplantation pregnancy failures. The long list of possible causes for the postimplantation pregnancy loss includes, among others, genetic abnormalities in fetus, anatomical abnormalities of the uterus, endocrinological insufficiency, and microbiological problems. However, more than 50% of recurrent miscarriages still have no recognized causes. The concept that many such abortions may be immunologically mediated has gained increasing support over the years. Moreover, immunization of such women with husband's or third party leukocytes has resulted in more than 70% of subsequent pregnancies resulting in live births. Since neither the mechanisms leading to pregnancy loss nor the success of immunotherapy are clear, the set-up of animal models for recurrent abortions would be of supreme significance. Our recent data show that immunopotentiation of maternal immune system by Complete Freund Adjuvant significantly improves pregnancy rate in CBA x DBA/2 mouse combination with high percentage of fetal resorptions. This effect is followed by decrease of IL 2 production in spleen; increase of MAC 1-positive cells at placenta; amplification of suppressive activity of local and systemic lymphocytes and by reverse of embryotoxic effect of maternal serum. Data obtained in this model seems to be valuable in substantiation of rationale for nonspecific immunotherapy of human abortions. PMID- 1741939 TI - Fertility impairment and improved fetal survival induced by a tumor cell line in mice. AB - The BL6-T2 tumor, a regressor melanoma line in C57BL/6J mice shown by us previously to be abortifacient, has been cloned in vitro. Clones obtained have been tested in vivo for tumorigenicity and effect on gestations, in order to correlate the immunogenicity of the tumor and its effect on fetal survival. Results demonstrate that high immunogenicity and impairment of fertility do not occur in the same tumor clones. We also show that this tumor produces and secretes GM-CSF and CSF-1 and that trophoblast cells express in situ mRNA encoding for the CSF-1 receptor. We consequently hypothesize that this tumor exerts its abortifacient effect not via its strong immunogenicity but via cytokines it secretes. PMID- 1741940 TI - Radiographic demonstration of the dislocated SC joint. PMID- 1741941 TI - Breast ductography in the investigation of nipple discharge. PMID- 1741942 TI - The use of macro-radiography in the initial examination of the petrous temporal region. AB - The results of the survey show that macroradiography of the petrous temporal region is not a common practice. However, the results of the tests show that an increase in discernible detail can be achieved with only a slight increase in geometrical unsharpness, no loss in resolution and, if departmental protocol is to produce AP images through the magnified orbits, a reduction of over 100 times in the radiation exposure dose to the lens of the eye by producing PA macroradiographs instead. Taking into consideration both the image quality of the macro-radiographs obtained, and the radiation exposure dose received by the lens of the eye, the most suitable macroradiographic technique has been implemented within the department as a routine procedure. PMID- 1741943 TI - Assessment of dose in computerised tomography. PMID- 1741944 TI - Costing radiology services. PMID- 1741945 TI - The use of thin metal filters to reduce dose to patients. PMID- 1741946 TI - Computed tomography in failed back syndrome. AB - A significant number of patients complain of recurrent symptoms following lumbar spine surgery. The main differential diagnosis is between post-operative epidural fibrosis and recurrent disc protrusion. Computed tomography is generally preferred to myelography for making this distinction, not least by the patient. Intravenous contrast medium can further improve diagnostic specificity. This article reviews the practical aspects and diagnostic accuracy of computed tomography in failed back syndrome, and draws attention to the potential pitfalls and less common abnormalities which may be encountered. PMID- 1741947 TI - Oral toxicity of formaldehyde and its derivatives. AB - Formaldehyde (FA) has been commercially produced since the early 1900s. Its widespread use in a variety of applications is known to result in appreciable exposure of workers and of a section of the general population. Formaldehyde is a normal metabolite in mammalian systems. It occurs in air as a product of the natural photooxidation of automobile exhaust, combustion processes, incinerators; formaldehyde has been found in municipal and industrial effluents and is present in food either naturally (fruits and vegetables, in the order of parts per million), or as a result of its use as a food additive. The use of FA and its derivative, hexamethylenetetramine (HMT), which gradually decomposes to FA under acidic conditions as antimicrobial agents in food, raises questions about their potential chronic oral toxicity. Furthermore, since FA is a very reactive compound and reacts with different macromolecules such as proteins and nucleic acids, the safety evaluation of FA as a cheese additive must take into account the toxicity of the reaction products between FA and milk components. Biochemical aspects, acute and short-term toxicity studies including mutagenicity, multigeneration, and reproduction studies, long-term carcinogenicity studies after oral administration of FA and HMT are reviewed in this paper. The results of these studies indicate that repeated oral exposure of a relatively large amount of FA that could overwhelm the normal metabolic capacity of animals to convert FA into formiate, CO2, and water produces histopathological gastric changes. This paper correlates the hazard caused by the exposure to low levels of FA, as far as its carcinogenic potential by oral route is concerned per se or regarding its use as a food additive. Based on the evidence that FA is formed naturally in food and is a normal mammalian metabolite and that a threshold for carcinogenicity exists both after exposure by inhalation and oral administration, it may be deduced that FA is not carcinogenic at low levels of exposure. PMID- 1741948 TI - The isolated perfused porcine skin flap as an in vitro model for percutaneous absorption and cutaneous toxicology. AB - The isolated perfused porcine skin flap (IPPSF) is a new perfused skin model which allows in vitro cutaneous pharmacology and toxicology studies to be conducted in a viable skin preparation which has a normal anatomical structure and a functional microcirculation. The purpose of this review is to (1) outline the background of this field which indicated the need for this type of model; (2) outline the surgical procedures needed to create and harvest viable preparations; (3) overview the criteria (biochemical, physiological, and histological) used to assess viability during an experiment; (4) present results of percutaneous absorption, cutaneous metabolism, transdermal delivery (passive and active), and skin distribution experiments conducted to date; (5) present the strategy developed to quantitate percutaneous absorption and cutaneous drug distribution using compartmental and physiological-based pharmacokinetic models; (6) assess the correlation of IPPSF data to in vivo results; (7) define the biochemical, physiological and histological (LM, TEM, enzyme histochemistry) response of the IPPSF to topically applied cutaneous vesicants; (8) overview where this type of in vitro model fits into the overall framework of cutaneous toxicology and pharmacology research; and (9) outline possible paths for future development. This review should provide the reader with an appreciation of some unique problems in this field which require an in vitro model that is closely integrated in structure and function to the in vivo setting. PMID- 1741949 TI - Nasal cavity enzymes involved in xenobiotic metabolism: effects on the toxicity of inhalants. AB - A decade ago, the ability of nasal tissues to metabolize inhalants was only dimly suspected. Since then, the metabolic capacities of nasal cavity tissues has been extensively investigated in mammals, including man. Aldehyde dehydrogenases, cytochrome P-450-dependent monooxygenases, rhodanese, glutathione transferases, epoxide hydrolases, flavin-containing monooxygenases, and carboxyl esterases have all been reported to occur in substantial amounts in the nasal cavity. The contributions of these enzyme activities to the induction of toxic effects from inhalants such as benzo-a-pyrene, acetaminophen, formaldehyde, cocaine, dimethylnitrosamine, ferrocene, and 3-trifluoromethylpyridine have been the subject of dozens of reports. In addition, the influence of these enzyme activities on olfaction and their contribution to vapor uptake is beginning to receive attention from the research community. Research in the next decade promises to provide answers to the many still unanswered questions posed by the presence of the substantial xenobiotic metabolizing capacity of the nasal cavity. PMID- 1741950 TI - Proteinuria: changes and mechanisms in toxic nephropathies. AB - During the last few decades, considerable progress has been made in the understanding of the pathophysiological mechanisms of proteinuria. A great variety of hemodynamic or biochemical mechanisms acting at different sites of the nephron have been shown to alter the renal handling and the urinary excretion of proteins. The finding which perhaps has had most practical implications is that the pattern of protein excretion quantitatively and qualitatively varies with the site and severity of renal damage. This has led to the development of a large array of methods for the identification and quantitation of specific urinary proteins. These methods have been most extensively used by toxicologists in experimental, epidemiological, or clinical studies on potentially nephrotoxic chemicals (e.g., drugs, heavy metals, solvents, etc.). The present review summarizes the current state of knowledge on the mechanisms of proteinuria and the use of urinary proteins as indicators of nephrotoxicity. PMID- 1741951 TI - Microalgae as food and supplement. AB - The microalgae Chlorella spp., Dunaliella spp., and Scenedesmus spp., and the cyanobacteria Spirulina spp., and Aphanizomenon flos-aquae, are being used as nutrient-dense foods and sources of fine chemicals. They have significant amounts of lipid, protein, chlorophyll, carotenoids, vitamins, minerals, and unique pigments. They may also have potent probiotic compounds that enhance health. Their historical and current use are reviewed in this article. PMID- 1741952 TI - The influence of food on food intake: methodological problems and mechanisms of action. AB - Emphasis has been placed on the understanding of the regulation of food intake in the hope of aiding the battle against obesity and of helping to ameliorate the anorexia of cancer and eating disorders. Available data suggest that the regulatory system is multifaceted and complex. This review focuses on current research on the regulation of appetite and satiety by carbohydrates, fats, and proteins as well as by artificial sweeteners. Some methodological problems and potential mechanisms of action at the biochemical level are discussed. Evidence suggests that organisms are more successful in defending against calorie dilution than in adjusting to increases in calories. The implications of that defense relative to the use of ersatz nutrients are explored. PMID- 1741953 TI - The effects of postharvest treatment and chemical interactions on the bioavailability of ascorbic acid, thiamin, vitamin A, carotenoids, and minerals. AB - All recent health recommendations include admonitions to reduce calories, maintain desirable weight, reduce fat, increase complex carbohydrates, and ensure an adequate intake of nutrients. Such recommendations require that we know not only nutrient composition of foods, but also potential losses and decreased bioavailability due to postharvest treatment and chemical interactions. This article discusses in some detail the reactions of concern that cause such changes and their potential alleviation with several key nutrients. The nutrients discussed were chosen as a result of the conclusions of the Joint Nutrition Monitoring Report of the Department of Health and Human Services and the U.S. Department of Agriculture. Obviously other choices could have been made, but the authors felt that the nutrients chosen--ascorbic acid, thiamin, vitamin A, carotenoids, calcium, and iron--were representative of a key profile of nutrients whose reactivity makes them vulnerable to losses in bioavailability, as well as being noted in the Joint Nutrition Monitoring Report. PMID- 1741954 TI - Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity. AB - While classical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase deficiency (3 beta-HSD) is a known cause of adrenal hyperplasia resulting in ambiguous genitalia and adrenal insufficiency at birth, nonclassical or late onset 3 beta-HSD deficiency is found in an important proportion of women with androgen excess. We have previously isolated and sequenced the cDNA and gene for the human type I 3 beta-HSD, which represents the main species expressed in the placenta and skin. Recently, we isolated, sequenced, and expressed the functional cDNA encoding type II 3 beta-HSD, which is the predominant 3 beta-HSD expressed in human adrenals and gonads. The present study describes the isolation and complete sequence of the corresponding type II 3 beta-HSD gene, which is the form most likely responsible for human 3 beta-HSD deficiency. The structural gene contains four exons of 57, 231, 165, and 1,214 bp, respectively, separated by introns of 128, 3,383, and 2,162 bp. DNA sequence analysis of the 5'-flanking region reveals the existence of two putative TATA boxes situated 28 and 140 nucleotides upstream from the transcription start site whereas two putative CAAT boxes are located 57 and 38 nucleotides upstream from the TATA boxes, respectively. A restriction fragment length pattern specific for each gene has been characterized. The present findings should provide the tools required for detailed analysis of the molecular basis of 3 beta-HSD deficiency as well as of normal sex steroid biosynthesis. PMID- 1741955 TI - Identification of nerve growth factor-responsive sequences within the 5' region of the bovine preprotachykinin gene. AB - The production of substance P and the mRNA encoding its precursor (preprotachykinin, PPT) is regulated by nerve growth factor (NGF) in dorsal root ganglion (drg) neurons. To explore the mechanism by which NGF regulates the production of PPT mRNA, we have transfected PC12 cells and F11 cells with plasmids containing the bovine PPT promoter linked to the reporter gene chloramphenicol acetyltransferase (CAT). We have identified (i) functional elements within the PPT promoter which are necessary for expression in the absence of NGF and (ii) two separate regions, each of approximately 250 bp, which confer NGF responsiveness. Both regions contained a sequence element, similar to a known transcription factor binding site, which is present in several other NGF regulated genes. PMID- 1741956 TI - Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15. AB - A cDNA encoding a novel human subtilisin-like protease was identified by a polymerase chain reaction (PCR) methodology. PCR primers were designed to be specific for the subfamily of eukaryotic subtilisin-like proteases with specificity for paried basic amino acid residue processing motifs. The gene encoding this protease, designated PACE4, also encoded a smaller subtilisin related polypeptide derived by alternate mRNA splicing. The deduced PACE4 protein sequence contained a number of interesting features not present in other family members, including an extended signal peptide region, and a relatively large carboxyl-terminal cysteine-rich region with no obvious membrane anchor sequence. As with the fur gene product, the tissue distribution of PACE4 was widespread, with comparatively higher levels in the liver. An additional relationship to the fur gene product was shown by chromosomal localization studies. The close proximity of the fur and PACE4 genes on chromosome 15 suggests that these genes probably evolved from a common ancestor by gene duplication. PMID- 1741957 TI - Analysis of active site motions from a 175 picosecond molecular dynamics simulation of camphor-bound cytochrome P450cam. AB - The structure and internal motions of the active site residues of camphor-bound cytochrome P450cam have been evaluated on the basis of a 175 psec molecular dynamics simulation. The active site residues generally show very small deviations away from their starting crystal positions. These residues also generally show much smaller fluctuations than for the enzyme as a whole. Phe 87 is dynamically very unusual and is suggested to play a role in substrate movement into and/or out of the active site. The average distance between the heme iron and atoms C5, C6, and C3 of camphor is 5.3, 6.0, and 7.0 A, respectively. This trend is consistent with the experimentally observed stereospecificity of the hydroxylation reaction. On the basis of distance and angle criteria, both 5-exo and 5-endo hydrogen abstraction are predicted to occur during the hydroxylation reaction; although the 5-exo pathway is expected to be 3-fold more likely. PMID- 1741958 TI - Charge grouping approaches to calculation of electrostatic forces in molecular dynamics of macromolecules. AB - Calculation of long-range electrostatic interactions is the most time-consuming step in theoretical simulation of the structure and dynamics of macromolecules. In practice very short cutoff distances are used, which may distort the behavior of the model system. We describe two accurate approaches to calculation of electrostatic forces based on hierarchical grouping of charges into cubes. The first is similar to the O(NlogN) algorithm developed by Barnes, J. and Hut, P., Nature (London) 324, 446-449 (1986), for simulation of a gravitational motion of N bodies. The second approach we formulate for a system with periodic boundary conditions in the nearest image approximation. The calculation of electrostatic interactions and a charge grouping procedure are faster than O(N2). The average inaccuracy in the force introduced by the grouping does not exceed 1%. We describe a small modification of the same approach which makes it suitable for long strongly charged polymers as well. This accurate approach to calculation of electrostatic interactions is illustrated with an example of the dynamics of ions near DNA. Quick equilibration of the ionic distribution is observed during molecular dynamics simulation if electrostatic forces are properly calculated, while the behavior and distribution of ions are less realistic when the conventional cutoff distances are used. PMID- 1741959 TI - Computer modelling studies on the mechanism of action of ribonuclease T1. AB - The mechanism of action of ribonuclease (RNase) T1 is still a matter of considerable debate as the results of x-ray, 2-D nmr and site-directed mutagenesis studies disagree regarding the role of the catalytically important residues. Hence computer modelling studies were carried out by energy minimisation of the complexes of RNase T1 and some of its mutants (His40Ala, His40Lys, and Glu58Ala) with the substrate guanyl cytosine (GpC), and of native RNase T1 with the reaction intermediate guanosine 2',3'-cyclic phosphate (G greater than p). The puckering of the guanosine ribose moiety in the minimum energy conformer of the RNase T1-GpC (substrate) complex was found to be O4'-endo and not C3'-endo as in the RNase T1-3'-guanylic acid (inhibitor/product) complex. A possible scheme for the mechanism of action of RNase T1 has been proposed on the basis of the arrangement of the catalytically important amino acid residues His40, Glu58, Arg77, and His92 around the guanosine ribose and the phosphate moiety in the RNase T1-GpC and RNase T1-G greater than p complexes. In this scheme, Glu58 serves as the general base group and His92 as the general acid group in the transphosphorylation step. His40 may be essential for stabilising the negatively charged phosphate moiety in the enzyme-transition state complex. PMID- 1741960 TI - Conformation of DNA-DNA polymerase I complex observed by scanning tunneling microscopy. AB - The conformation of a complex of a 41 mer/31 mer DNA fragment and the Klenow fragment of DNA polymerase I of Escherichia coli was studied by scanning tunnelling microscopy (STM). The results shows that near two turns of double helix of this DNA fragment was outside of enzyme while another part containing more than one turn of helix and 10 nucleotides single strand was combined with enzyme. The dimension and shape of DNA polymerase I (KF) in complex were different from that of free enzyme. The conformation of DNA-DNA polymerase I (KF) complex and the application of STM in studying structure of complex of DNA polymerase with DNA were discussed. PMID- 1741961 TI - An effective enzyme interacting with poly (dT-dA).poly (dT-dA): a dynamic enhancer-repressor action. AB - The Green function technique is used to study the open hydrogen bond probability of poly(dT-dA).poly(dT-dA) when an effective enzyme is attached to the helix. The DNA interstrand hydrogen bond mean motion and probability of fluctuating to an open state depends on the internal vibrational frequency of the enzyme. An enzyme with internal frequency of 80 cm-1 reduces hydrogen bond motion and the resulting probability of hydrogen bond fluctuational opening. An enzyme with internal frequency of 72 cm-1 increases hydrogen bond motion and the probability of hydrogen bond breaking. PMID- 1741962 TI - Molecular structure of antitumor drug steffimycin and modelling of its binding to DNA. AB - The molecular and crystal structure of steffimycin have been determined by single crystal X-ray diffraction to 0.9 angstrom resolution. The triclinic crystals are in the space group P1, with the unit cell dimensions of a = 8.606(3) angstrom, b = 22.168(7) angstrom, c = 8.448(2) angstrom, alpha = 97.56(3) degrees, beta = 95.97(2) degrees, gamma = 87.94(3) degrees, Z = 2. The structure was solved by direct methods and refined by the full-matrix least-squares method to a final R value of 0.065 with 3405 (Inet greater than 2.0 sigma (Inet] observed reflections using the NRCVAX software package. The crystal lattice includes 2 independent steffimycin, 3 water and one 2-methyl-2,4-pentanediol molecules. The conformation of steffimycin is grossly similar to other anthracycline antibiotics including daunorubicin. The crystal packing interactions of steffimycin suggest a preferred stacking of the aglycone chromophore of the antibiotic which resembles the intercalative interactions seen in the daunorubicin-d(CGTACG) (Wang et al., Biochemistry 26, 1152 (1987] and nogalamycin-d(CGT(pS)ACG) (Liaw et al., Biochemistry 28, 9913 (1989] complexes. The atomic coordinates data from these complexes were used to model the intercalative binding of steffimycin to DNA. The models were then stereochemically idealized by the constraint refinement program NUCLSQ. Subsequently XPLOR software package was used for energy minimization of these models in vacuo. The model building studies suggest that steffimycin has a higher CpG base sequence specificity over the TpA step, similar to that of daunorubicin and nogalamycin. PMID- 1741963 TI - Site-specific interaction of the antitumor antibiotic dynemicin with branched DNA molecules. AB - A specific interaction of stable branched DNA molecules with the antitumor antibiotic dynemicin is reported. Dynemicin contains an anthraquinone and an enediyne unit, and belongs to the family of enediyne antitumor agents. DNA strand scission by dynemicin appears to involve interaction of the anthraquinone core with DNA and release of a phenyl diradical from the enediyne core that can abstract hydrogen atoms from the sugar phosphate backbone of DNA. The cleavage patterns of each labeled strand in two branched tetramers of four 16-mers are compared with those of the same strands in unbranched duplex controls. Differences between the profiles corresponding to scission of branched and duplex DNA molecules can be detected in most of the strands. The strongest differences define a specific site flanking the branch in each of two branched structures. At 18 degrees C, cleavage at strand positions demarcating the site of enhanced affinity in both junctions is observed to be 70-100% more efficient than at the corresponding sequence positions in the control duplex DNA molecules. The patterns of preferential cleavage at these sites are significantly altered in the presence of excess propidium diiodide, an intercalative drug. PMID- 1741964 TI - Determination of DNA cleavage specificity by esperamicins. AB - The esperamicins are members of a class of potent antitumor antibiotics that contain stained diacetylenic ring systems capable of forming DNA-cleaving diradicals upon reaction with thiols. Here we show that the diacetylenic ring core itself determines the sequence specificity for scission of duplex DNA): esperamicin A1, and three products of hydrolysis of the glycon, esperamicins C, D, and E, are found to retain a common sequence preference. The sugar residues exert a strong influence on the cleavage efficiency, presumably by interacting nonspecifically with DNA. The presence of a branch in the DNA is found locally to inhibit scission by esperamicins, and this effect is shown to be due to the core also. PMID- 1741965 TI - DNA-bending on ligand binding; change of DNA persistence length. AB - This paper simulates the helix-characteristic changes of apparent DNA persistence length caused by randomly distributed helix bends as induced, e.g., by DNA-bound ligand molecules. The parameters varied are the constant angle gamma of helix bending and the size alpha of the DNA drug binding site, but also the degree of DNA-ligand binding cooperativity and the helix-unwinding angle. If the size of the binding site is comparable with the helix pitch, the influence of phasing between helix bends and helix screw upon the apparent persistence length is obvious. In the accompanying paper experimental data are analyzed in terms of this theoretical background. PMID- 1741966 TI - DNA-helix bending, stiffening and elongation on ligand binding; analysis for several DNA-drug systems, general viscometric DNA response and stereochemical implications. AB - For several DNA-ligand systems the DNA helix bending, stiffening and elongation behaviour is treated quantitatively. The experimental basis are viscosity data from literature as a function of r, the ratio of drug molecules bound per DNA monomer unit. If the relative viscosity changes delta y1(r) and delta yh(r) for DNA of low and high molar mass, respectively, are known, the relative changes of contour length, delta L/L degrees, and of persistence length, delta a/a degrees, can be evaluated as a function of r, as repeatedly demonstrated. For random sequence-independent interactions, helix-bending is reflected by a helix-typical increment of delta a/a degrees (r), being zero at r = 0 and also at DNA saturation by bound ligand molecules [Reinert, Biophysical Chemistry 13, 1-14 (1981)]. This characteristic DNA behaviour often enables us to separate the bending and the stiffening increment of delta a/a degrees. The theoretical treatment of this problem (Schutz and Reinert, J. Biomolec. Struct. & Dynam. 9, 315-329, 1991) now permits a more detailed study of the ligand-induced DNA bending. The ligand-DNA systems treated here concern the following drugs (in parentheses DNA bending angle at low r-values): proflavin (8 degrees), daunomycin (11 degrees), aclacinomycin A (9.7 degrees, on cooperative interaction), actinomycin D (16 degrees), mitomycin C (16 degrees), a double intercalating bisphenantridine (12 degrees), 9-deacetyl-daunomycin (8 degrees) and 9-epi deacetyl-daunomycin (12-18 degrees). We also demonstrate that the consideration of the DNA flexibility and its change on interaction of short DNA molecules with intercalating drugs delivers helix elongation values in better accord with the theoretical value. In the Appendix, a catalogue of simulated delta y(r) dependences is given for both short and long DNA molecules. It systematically describes the DNA viscosity response upon typical DNA stiffening, elongation, and helix-bending effects. PMID- 1741967 TI - The flexibility of A-form DNA. AB - We have determined the rise per base pair and persistence length of A-form DNA in trifluoroethanol solutions for fragments 350-900 base pairs in length that best describe rotational diffusion coefficients determined by transient electric birefringence. The 2.6 A spacing between base pairs found in crystal and fiber A form structures is preserved in solution. The persistence length is about 1500 A, or about three times longer than for B-form DNA. There is no apparent electrostatic contribution to the persistence length in the salt concentration range 0.2-2.0 mM Na cacodylate. This suggests an even closer association between DNA and its neutralizing counterions than predicted by condensation theory, perhaps due to a sheath of trifluoroethanol excluded water surrounding the A-form helix. PMID- 1741968 TI - Molecular dynamics simulations of dinucleoside and dinucleoside-drug crystal hydrates. AB - Molecular dynamics simulations have been performed on the dinucleoside monophosphates rGpC and dCpG, the latter in its intercalation complex with the acridine drug proflavine. The simulations were performed on the crystal structures, with crystallographically-located solvent molecules. It was found that satisfactory results were best obtained with restraints placed on the movements of the water molecules. Motions of individual atoms have been examined in terms of rms fluctuations and anisotropy and correlation functions. Relative motions of groups (phosphates, sugars, bases and proflavine molecules) have been analysed. PMID- 1741969 TI - Distribution of simple repetitive (TG/CA)n and (CT/AG)n sequences in human and rodent genomes. AB - Sixteen million nucleotide sequence of genome of various organisms have been analysed to detect and study the extent of occurrence of simple repetitive sequences. Two sequence motifs (TG/CA)n and (CT/AG)n capable of adopting unusual DNA structures, left handed Z-conformation and triple-helical conformation respectively, are found to be abundant in rodent and human genomes, but almost completely absent in bacterial genome. (TG/CA)n and (CT/AG)n sequences are present mostly in the intron or 5'/3' flanking regions of the genes. The presence of such repeat motifs in genomic sequence of higher eukaryotes has been correlated with their possible functional significance in nucleosome organization, recombination and gene expression. PMID- 1741970 TI - Improved chips for sequencing by hybridization. AB - The SHOM method (Sequencing by Hybridization with Oligonucleotide Matrix) developed in 1988 is a new approach to nucleic acid sequencing by hybridization to an oligonucleotide matrix composed of an array of immobilized oligonucleotides. The original matrix proposed for sequencing by SHOM had to contain at least 65,536 octanucleotides. The present work describes a new family of matrices, which allows one to reduce the number of synthesized oligonucleotides 5-15 times without essentially decreasing the resolving power of the method. PMID- 1741971 TI - Renal-hepatic-pancreatic dysplasia and its variants. AB - A family is reported, in which two pregnancies resulted in the birth of a female fetus with multiple congenital anomalies, including renal cystic dyplasia, pancreatic fibrosis with dilated pancreatic duct, and some anomalies of the face and genitalila. The pathology of the second fetus was revealed by prenatal ultrasonographic examination. In the relevant literature 20 additional cases of renal-hepatic-pancreatic dysplasia (RHPD) could be found. It is demonstrated that cystic renal dysplasia associated with pancreatic fibrosis or cystofibrosis (with normal liver) as well as cystic renal dysplasia associated with hepatic fibrosis (with normal pancreas) should be considered as incomplete RHPD variants. In 6 cases out of 22, the infants had some features of the apolysplenia complex, including situs inversus and/or heart defects. The association of RHPD and apolysplenia has been proved to be an autosomal recessively inherited syndrome. Most probably RHPD without apolysplenia represents a separate entity with autosomal recessive mode of inheritance as well. PMID- 1741972 TI - A child of high intelligence with the Johanson-Blizzard syndrome. AB - In this article, a boy is presented with the Johanson-Blizzard syndrome and high intelligence. In the literature, a wide range of intellectual abilities of children with the Johanson-Blizzard syndrome is reported. To obtain optimal conditions for the development of a child with the Johanson-Blizzard syndrome, early diagnosis of potential problems that may prevent this normal growth and development is recommended. The acquisition of more knowledge concerning the hypothetic reasons for intellectual impairment is of vital importance for families involved, in the light of genetic counseling. PMID- 1741973 TI - Deletion of 7q22 and ectrodactyly. AB - We report the case of an infant with 3-limb ectrodactyly and a deletion of most of 7q22. This observation, along with 4 similar cases from the literature, suggests the presence of a locus affecting limb differentiation in 7q22 near to the proximal interface. PMID- 1741974 TI - Genetic service in Byelorussia. PMID- 1741975 TI - Behavioral and emotional problems in youngsters with Prader-Willi syndrome. AB - In this study we document the behavioral/emotional problems of 27 Prader-Willi syndrome (PWS) subjects assessed with the Achenbach Child Behaviour Checklist. Compared with normal subjects of the same age and sex, PW subjects showed significantly more problem behaviour. Of the PWS subjects 87% had total problem scores in the clinical range. No significant difference was found in the proportion of Prader-Willi patients scored in the clinical range on the Internalizing over the Externalizing syndrome. The need for systematic attention towards behavioral/emotional problems when PWS patients enter adolescence is emphasized. PMID- 1741976 TI - Cerebro-oculo-facio-skeletal (COFS) syndrome. The variability of presenting symptoms as a manifestation of two subtypes? AB - In this paper we present two female newborns with the cerebro-oculo-facio skeletal (COFS) syndrome. The variability of presenting symptoms and differences in clinical evolution of the two infants favour the suggestion of Preus that two subtypes of this autosomal recessive inherited syndrome may exist. PMID- 1741977 TI - Noonan phenotype in the basal cell nevus syndrome. AB - In this report we present a three-generation family in which five members present the basal cell nevus syndrome. In three of them a Noonan phenotype was present. The basal cell nervus syndrome is another example of a neural crest dysplasia associated with a Noonan-like phenotype. This observation supports the theory that the autosomal dominant mutation causing the neural crest dysplasia may lead to a Noonan-like phenotype. PMID- 1741978 TI - Intelligence and the fra(X) syndrome: a review. AB - In this paper we review the data on intelligence in fra(X) males reported up to now in the literature, with special attention to its evolution with age. The available data suggest a decline in intellectual functioning in relation to age. These findings, however, should be interpreted with caution because of sampling and other methodological problems related with the fra(X) screening procedures and programs in general. PMID- 1741979 TI - A hydropic fetus with translucent ribs, arthrogryposis multiplex congenita and congenital myopathy: etiological heterogeneity of A.M.C., Toriello-Bauserman type? PMID- 1741980 TI - Role of gonadal dysgenesis in gonadoblastoma induction in 46, XY individuals. The Leuven experience in 46, XY pure gonadal dysgenesis and testicular feminization syndromes. AB - To stress the importance of gonadal dysgenesis in the genesis of gonadoblastoma in the presence of the Y-chromosome, the authors report their experience on 7 patients with 46, XY Pure Gonadal Dysgenesis (PGD) and 14 patients with complete or incomplete forms of Testicular Feminization (TF) syndrome. The diagnostic criteria and the clinical and pathological findings are reviewed. Four patients with PGD were found to be affected by bilateral (1 patient) or unilateral (1 patient) gonadoblastomas, and by extragonadal (1 patient) or gonadal (1 patient) dysgerminoma, whereas no gonadal tumors were encountered in testes of patients with complete (CTF) or incomplete (ITF) forms of TF, underlining the pathogenic role of the gonadal dysgenesis. PMID- 1741981 TI - How adequately are nurses being prepared for their health teaching role? AB - Forty-five Australian faculties and schools of nursing were surveyed by questionnaire to gain information about the health education component of undergraduate and postgraduate programs, and about current research activity relating to the educational role of nurses. Response rate achieved was 69%. Almost all institutions indicated involvement in preparing nursing students for an educational role, yet only five respondents described research activity relating to this. Most preparation was provided in an integrated context rather than in separate course units and the length of time allocated varied substantially. Responses to questions about content and clinical experiences were often omitted or were very general, with those involved in providing separate courses being much more likely to supply detailed or specific information. It is hypothesised that in general nurses are graduating from Australian colleges and universities inadequately prepared for the health educator role. PMID- 1741982 TI - Bacterial contamination of three-way taps--one Australian hospital's experience. AB - The incidence and types of organisms present in the vacant ports of 424 three-way taps were studied. The taps were used in 50 children in ICU. Twenty-five (6%) of the taps showed organism growth of one to three colonies from swabs taken of one or more vacant ports. The organisms cultured were staphylococci, klebsiella, streptococci, bacilli and fungi. While there was no marked difference in the growth rate of organisms in three-way taps used in intravenous, intra-arterial and central venous lines, growth rate increased with duration of use. PMID- 1741983 TI - Augmentation mammaplasty: neither simple nor safe. AB - Elective aesthetic cosmetic surgery of the female breast appears not to warrant the same attention to informed consent or authorisation as other surgical procedures. Arguments for benefits do not need to be persuasive since the prospective patient is usually 'sold on the idea'. This paper argues that more rather than less information is necessary where the surgery will not achieve what is claimed for it and where there are significant risks of harm. Evidence is presented to show that augmentation mammaplasty does not provide a solution to problems of body image, self-esteem and sexuality; it may result in considerable pain, suffering, financial and emotional cost, interference with life choices and a loss of trust in health care professionals. In view of the emerging data which points to the doubtful efficacy and safety of the procedure and the prosthetic devices, and since elective cosmetic surgery is said to be a growth industry, checks and balances need to be in place to ensure women are informed participants in decision-making. They require the best possible advice, care and support and nurses could play a more proactive role as patient advocates. PMID- 1741984 TI - A Delphi survey of clinical nursing research priorities in Western Australia. AB - In 1989-1990 an investigation was undertaken to ascertain which problems WA nurses considered required researching. A modified Delphi technique was employed to obtain data from nurses in hospitals and health care agencies throughout the metropolitan and rural regions in the state. Participants worked in areas of acute care, mental health, paediatrics, gerontology, community health and domiciliary services and addictions. Problems identified were categorised into three streams; clinical, management and staff development. Respondents were required to assign a value to items according to their importance to nurses and to patients. They were also asked to indicate whether they considered there was an adequate research base relevant to each item. Results reported here are based on the 10 priority items identified in the clinical stream. PMID- 1741985 TI - Preoperation interviews: a nursing intervention to reduce patients' anxiety. AB - A quasi-experimental study was conducted to evaluate the effect of preoperative interviews on patients' anxiety levels. A convenience sample of 60 was assigned between two groups of equal size: a treatment group in which subjects were interviewed by a perioperative nurse or a control group in which subjects were not interviewed. All subjects completed state-trait Anxiety Inventory questionnaires. Group comparison using analysis of covariance showed subjects who were interviewed by the perioperative nurse reported significantly less anxiety than control group subjects. PMID- 1741986 TI - Developing methods and research instruments for assessing physical and psychosocial outcomes of patient care as a function of nursing staff mix. AB - This paper describes a study which assesses a wide variety of both physical and psychosocial outcomes of patient care against nursing care standards, and as a function of two different staff mixes--an 80% registered nurse (RN) 20% enrolled nurse (EN) mix and an all-RN staffing regimen. The study is divided into three stages: Stage I which concerned the design of the investigation and development of research instruments and procedures; Stage II which concerned the field testing of all research procedures and assessment of the reliability of research instruments and Stage III which will constitute the main study and is presently being conducted in an acute medical and an acute surgical ward. This paper is confined to a report on Stages I and II and provides the conceptual framework for the study, a description of the research instruments and the ways they were developed and a description of the research methods. The results from Stage II show that the principal research instruments are highly reliable with coefficients always in excess of 0.80, and that all of the research methods and procedures are practical and feasible. The study is significant because outcome based evaluations, while attractive in principle, are in their infancy and little guidance appears in the literature about how to conduct these types of investigations. This paper attempts to address this deficiency. PMID- 1741987 TI - Influences on instructional planning. AB - This study investigated the influences on instructional planning decisions of nurse academics in 12 Colleges of Advanced Education in New South Wales. Questionnaires were completed by 195 respondents and 14 nurse academics in four colleges were interviewed. Questionnaire data were analysed for trends and transcripts of the interviews were analysed for significant themes. The major constraining influences were found to be funding, workload and lack of time. Strong facilitating influences were found to be the academics' backgrounds and their beliefs concerning teaching, nurse academics, student needs, and learning. Other facilitators were heads of nursing schools, interpersonal relationships with people in nursing departments, beliefs about knowledge, students, teaching resources and 'ideal' curricula. The implications of findings for nursing academia, the utility of facilitating factor theory and confirmation of frame theory are discussed. PMID- 1741988 TI - Standardised clinical evaluation using Bondy rating scale. AB - A clinical performance evaluation tool adapted from Bondy's rating scale was used to assess all 680 second and third year students in the nursing program of a large metropolitan university. Second year students achieved an average score of 3.98 (out of 5), indicating that they were practising at a supervised level. Third year students' average score was 4.37, demonstrating an increased level of independence in clinical practice. The results were constant over two years of student assessments. Clear demarcation points identifying 'at risk' students were found (3.5 for second years and 3.9 for third years) facilitating remediation for this group. Criterion referenced definitions were especially useful when a wide range of clinical placements and several assessors were involved as they allowed consistent assessment of students' progress. PMID- 1741989 TI - Renal function in one-kidney, one-clip hypertension and low renin essential hypertension. AB - One-kidney, one-clip hypertension (1-K, 1-C HT) is initiated by increased preglomerular resistance which decreases nephron perfusion and causes several intrarenal changes that lead to increased mean arterial pressure (MAP). Elevated MAP serves to return nephron perfusion and sodium excretion to normal, so that fluid intake and output are balanced. Increased MAP usually occurs through volume homeostasis mechanisms that initially raise cardiac output and later elevate total peripheral vascular resistance via autoregulatory adjustments. However, if adequate volume is unavailable because of sodium restriction, sustained activation of the renin-angiotensin system increases blood pressure sufficiently to restore nephron perfusion. Thus, depending upon the availability of volume, renal perfusion and sodium balance can be restored either by volume retention or by increased angiotensin II (ANGII) formation and peripheral vasoconstriction. Similarities exist between 1-K, 1-C HT and low-renin essential hypertension (LRHT). In both cases, renal-pressure natriuresis is shifted to higher levels and there are marked increases in preglomerular resistance that necessitate increased MAP to maintain sodium balance. However, in 1-K, 1-C HT, there is a parallel shift of pressure natriuresis with little or no change in the slope of this curve, similar to that found in the normal-renin essential hypertension. In LRHT the slope of pressure natriuresis is decreased, indicating that blood pressure is much more salt sensitive than normal. Another difference is that PRA is low compared to normal PRA in 1-K, 1-C HT after compensatory increases in MAP. There is also no indication of glomerular membrane damage in 1-K, 1-C HT, whereas LRHT may have significant glomerulopathy, especially as hypertension progresses. These differences suggest that there may be additional factors besides preglomerular vasoconstriction involved in the etiology of LRHT. One possible factor is a reduction in nephron number in LRHT. Decreased functional nephrons would lead to glomerular hyperfiltration and increased distal tubular flow rate in the remaining nephrons, causing decreased PRA and eventually glomerular damage. Increased fractional sodium reabsorption, particularly in distal tubular segments, could also contribute to decreased PRA and cause blood pressure to be salt sensitive. These abnormalities, along with preglomerular vasoconstriction, may explain many of the characteristics of LRHT. PMID- 1741990 TI - Sodium retention and volume expansion as mechanisms. AB - After nephrectomy, the level of arterial pressure is determined by the permitted degree of fluid volume expansion. With kidneys present, the fundamental requirement for fluid volume homeostasis is met by maintaining the balance between sodium and water intake and output. When one-kidney, one-clip (1-K,1-C) hypertension develops on a free diet, early sodium retention occurs with transient increase in extracellular (ECFV) and plasma (PV) volumes, which may persist into the chronic stage. In sodium deprivation, hypertension is not inhibited and ECFV and PV are not significantly raised. Thus, when sodium is available, sodium retention may contribute to the hypertensive mechanism, but when unavailable, other mechanisms must be largely, if not wholly, responsible. When hypertension is reversed by unclipping, the immediate fall in blood pressure is attributable to reduction first in cardiac output and second in peripheral resistance, accompanied by diuresis and contraction of PV: but if external fluid balance is maintained, cardiac output and blood pressure still fall, although at a slower rate, indicating that factors other than volume are implicated. In the development of hypertension, the hemodynamic changes are the reverse of those on unclipping, with transient increase in cardiac output associated with increased myocardial contractility and decreased venous capacity which, when coupled with fluid retention, raise mean circulatory filling pressure. In conclusion, the kidney possesses many mechanisms for raising pressure and reestablishing sodium homeostasis including not only sodium retention, but also release of pressor hormones, renin and possibly others, enhanced afferent sympathetic activity and suppression of the release of medullary hypotensive factors. PMID- 1741991 TI - On the mechanisms and clinical relevance of one-kidney, one-clip hypertension. AB - Dr. Skeggs demonstrated the lack of renin dependence in 1-kidney, 1-clip hypertension and elucidated some of the differences between that and Dr. Goldblatt's classic 2-kidney, 1-clip model of hypertension. Studies of these two different types of hypertension have led research in many new directions and helped to reveal the role of the renin-angiotensin system in hypertension and that system's interaction with sodium-induced vasodilation in both animals and humans. More recent research has investigated the processes behind essential hypertension and I present here the proposal that, due to nephron heterogeneity, essential hypertension in humans is parallel in its pathophysiologic processes to Goldblatt hypertension. PMID- 1741992 TI - The medullipin system of blood pressure control. AB - The medullipin system of BP control has its cellular component in the renomedullary interstitial cells (RICs) of the renal papilla. The RICs secrete medullipin I which is conveyed to the liver to be activated into Med II. This activation appears to involve the cytochrome P-450 dependent enzyme system of the liver. Med II is a vasodilator that suppresses sympathetic tone, causes diuresis natriuresis and has a suppressive effect on the central nervous system (CNS). As such, Med II has biologic actions the exact opposite of major actions of the renin-angiotensin system. Angiotensin II is a vasoconstrictor that facilitates sympathetic tone, causes salt water retention by the kidney and has stimulatory effect on the CNS. These are double feedback BP control systems. One elevates the BP and is prohypertensive; the other lowers BP and is antihypertensive. Unclipped (UC) the one-kidney, one-clip hypertensive rat has assisted greatly in elucidating the medullipin system. The support for these contentions are documented in this presentation. PMID- 1741993 TI - Physiological effects of the humoral renomedullary antihypertensive system. AB - In experiments on rats, the physiological effects of the antihypertensive humoral system of the renal medulla were explored. We studied the parameters of blood pressure, heart rate, efferent sympathetic nervous activity to the splanchnic region, diuresis and natriuresis. The experimental situations included studies on normotensive rats, injected with extracted renomedullary lipids (medullipin), and normotensive rats extracorporally cross-perfusing an isolated kidney at increased pressure levels, to explore the release of renomedullary depressor substances. Spontaneously hyperactive rat (SHR) kidneys were also cross-perfused to study whether the renomedullary mechanism was reset upwards in this type of primary hypertension. Finally, the acute pressure reductions caused by angiotensin converting enzyme (ACE)-inhibitors were studied in intact and chemically medullectomized (2-bromo-ethylamine hydrobromide) rats to explore whether they were at least in part dependent on an intact renal medulla. In normal kidneys the renomedullary depressor system was initiated already at physiological pressure levels (at or above 100 mm Hg), causing the following humorally induced response pattern: the blood pressure fall was associated with decreases in both heart rate and sympathetic activity, while diuresis and natriuresis increased. In SHR kidneys, perfusion pressure had to be raised between 200 and 250 mm Hg before this depressor pattern was activated, revealing an "upward renomedullary resetting" well beyond the prevailing SHR blood pressure. The acute blood pressure decrease initiated in normotensive rats by an ACE-inhibitor (enalaprilat) was abolished in medullectomized rats, indicating an interaction between the renin-angiotensin and the renomedullary antihypertensive systems. PMID- 1741994 TI - The role of extrarenal renin in Goldblatt hypertension. AB - Renin-like activity can be demonstrated in arterial extracts from normal rats and from rats with Goldblatt hypertension. We have found no evidence, however, for elevated arterial renin levels in relation to plasma renin activity. Studies of the reversal of renovascular hypertension indicate that the fall in blood pressure produced by renal artery deconstriction is not renin-dependent. However, molecular biological techniques indicate that extrarenal renin gene expression is altered in some tissues, such as the adrenal gland in Goldblatt hypertension, and it is possible therefore that extrarenal renin synthesis is important in blood pressure control. This has to be distinguished from renin derived from plasma uptake. PMID- 1741995 TI - On the role of renin in one-kidney, one-clip hypertension. AB - It is known that the renin angiotension system as it is usually understood is not the mediator of experimental one-kidney, one-clip (1K,1C) hypertension in animals. There is also ample evidence that the blood pressure of dogs and rabbits with this form of hypertension can be lowered by immunization with hog renin, which implies that renin is the mediator. In an effort to resolve this contradiction, we searched for a second hypertensive substance which we thought may have been present in the crude hog kidney extracts that had been used to immunize the hypertensive animals. Instead, we ultimately discovered that the blood pressure of hypertensive rabbits could be lowered by immunization with pure hog renin. This remarkable finding could be explained if renin were transformed in vivo, exhibiting new antigenic sites and eliciting a second antihypertensive antibody. We found such an antibody. When free of antirenin, it lowered the blood pressure of 1K,1C hypertensive rabbits. The same antibody stained the cytoplasm of vascular smooth muscle cells and certain other cells in the tissues of normal and hypertensive rabbits. The presence of this transformed renin in the tissues of the rabbit was confirmed by chronic infusion of 125I-labeled renin into hypertensive rabbits. A significant portion of the radioactivity was found to be incorporated into a very high molecular weight, insoluble form. Its function in this location is unknown but must directly or indirectly involve vasoconstriction since its neutralization by specific antibody lowers the blood pressure of 1K,1C hypertensive rabbits. PMID- 1741996 TI - Sickness insurance (or prepaid illness care) PMID- 1741997 TI - Resident interest in physical medicine and rehabilitation fellowships. Results of a survey. AB - Physiatry, one of the six medical specialties that does not currently offer added or special qualification certification examinations, does not have accredited fellowships in potential subspecialty areas. These issues are currently being debated by the leadership organizations within physical medicine and rehabilitation such as the Association of Academic Physiatrists, the American Academy of Physical Medicine and Rehabilitation, the Physical Medicine and Rehabilitation Residency Review Committee and the American Board of Physical Medicine and Rehabilitation. Recent events, such as the establishment of funding agencies with an interest in medical rehabilitation research training, suggest that physiatric fellowships may become more available. A survey was conducted to determine whether physiatric residents desire postresidency training and, if interested, what type of additional training they would seek. This information could be used in formulating policies regarding the establishment, accreditation and certification of subspecialty fellowships within physical medicine and rehabilitation. Of 968 physiatric residents currently in training, 525 (54%) responded to a 22-question survey assessing resident interest regarding fellowship training, the different subspecialty areas, salary expectations, fellowship duration, preferred amount of time devoted to clinical v research work, mentorship, double boarding, accreditation, certification and a section for general comments. The results of the survey indicate considerable interest in fellowship training, which diminishes as residents approach graduation. Residents favored clinically oriented fellowships of 1-yr duration, which should be accredited and certified. Sports medicine was identified as the area of greatest subspecialty interest. PMID- 1741998 TI - Stiff-legged gait in spastic paresis. A study of quadriceps and hamstrings muscle activity. AB - Stiff-legged gait, ascribed to limited knee flexion during swing in spastic paresis, has previously received little detailed investigation. In this study, data from 23 patients referred for dynamic electromyographic evaluation of spastic stiff-legged gait were analyzed to identify timing of the activity of eight muscles during the gait cycle. Stride characteristics and foot switch data were also analyzed. Inappropriate activity in at least one of the quadriceps muscles during the preswing and/or initial swing phases was found in all 23 patients. Nine patients (39%) had hamstring activity during preswing. This group of 9, compared with the other 14 patients, had a significant reduction in average gait velocity and stride length (P less than 0.05) suggesting that preswing hamstring activity in stiff-legged gait may be counterproductive. No relation was found between biceps femoris (short head) activity and the amount of peak knee flexion attained in swing indicating that other factors are more important in attaining knee flexion. Delayed heel rise was observed in 21 patients (91%), which could imply insufficient calf muscle strength. Further, patients with markedly delayed heel rise achieved less peak knee flexion in swing than patients with normal or only moderately delayed heel rise (P less than 0.05). This may support the notion that adequate calf muscle strength is important in initiating knee flexion in the terminal stance/preswing phase. Results from this study provide preliminary quantitative information about stiff-legged gait that may prove useful in guiding management techniques. PMID- 1741999 TI - Relationship between electromyographic activity of the vastus lateralis while standing and the extent of bilateral simulated knee-flexion contractures. AB - The effect of simulated bilateral knee-flexion contractures (KFC) on the electromyographic (EMG) activity of the vastus lateralis was studied by testing 10 normal subjects using surface EMG to test the hypothesis that the activity of the knee extensors would increase as a function of the severity of the contracture. The root mean square of the EMG activity was determined from four 4 s samples taken at 30-s intervals, during 2 min of standing in each of five positions of simulated KFC (0 degree, 10 degrees, 20 degrees, 30 degrees and 40 degrees). A randomly balanced order of conditions was used. KFC were simulated in each subject by means of an adjustable line from the subject's waist to the sole of each foot. An analysis of variance was used to contrast EMG activity, and a significant difference was found between each of the positions (P less than 0.05). The mean (+/- 1 SD) EMG activity, expressed as a percentage of the maximum voluntary contraction, was 0.3% (+/- 0.2) at 0 degree, 7.6% (+/- 5.6) at 10 degrees, 10.9% (+/- 7.6) at 20 degrees, 16.6% (+/- 12.4) at 30 degrees and 24.0% (+/- 14.0) at 40 degrees. A linear relationship was found (r2 = 0.986), expressed by the equation y = 0.62 + 0.56 x, where y represents EMG activity and x represents the extent of simulated KFC (P = 0.0007). The results provide insight into the increased knee extensor activity necessary to stand with KFC and underline the importance of treating this common disorder. PMID- 1742000 TI - The injured upper extremity and the JAMAR five-handle position grip test. AB - Niebuhr and Marion (Am J Phys Med Rehab 1990;69:96-101) recently presented a study that utilized healthy subjects who were able to control the amount of force exerted during submaximal grip strength efforts. Stokes (J Occup Med 1983;25:683 684) proposed that a true weakness of grip can be distinguished in the injured upper extremity from a feigned effort that yields a flat horizontal type of curve. The purpose of this study was to evaluate the five-handle position JAMAR grip test in an injured population and compare the curves produced with a group of healthy subjects. We found that the patients with well-documented pathology produced a curve that was similar in shape to the healthy group; however, the curve on the injured extremity was reduced in force output. PMID- 1742001 TI - Noninflammatory knee joint effusions in spinal cord-injured and other paralyzed patients. Four case studies. AB - Four patients with knee effusions are described. Three had spinal cord injuries and the fourth had Guillain-Barre syndrome. Of the spinal cord-injured patients, the effusions were unilateral in one case and bilateral in another. The third patient developed effusions on two separate occasions with bilateral involvement once and unilateral involvement once. The patient with Guillain-Barre syndrome had bilateral knee joint effusions. All effusions were tapped and revealed type I synovial fluid except for one joint that contained some blood cells. Two of the three spinal cord-injured patients had heterotopic ossification at the knees documented by 99mTe bone scans and two were lying prone for the treatment of decubitus ulcers. Similar knee joint effusions have been described by several authors in the past. The etiology is unknown; however, we offer the hypothesis that paralysis of the muscles adjusting intra-articular knee joint structures may be the cause. It is important for clinicians to recognize that benign knee joint effusions are likely to be encountered in paralyzed patients. They can be evaluated with a simple synovial fluid analysis. PMID- 1742002 TI - Deep vein thrombosis in rehabilitating stroke patients. Incidence, risk factors and prophylaxis. AB - A total of 503 consecutive cases of suspected stroke were examined for potential eligibility based on recent development of a paralyzed limb. Of 123 otherwise eligible subjects, 22 were found by ultrasound to have deep vein thrombosis (DVT) on admission. Therefore, 101 patients were assigned randomly to one of the treatment groups or to the control group. The three treatments were adjusted-dose heparin, external pneumatic compression and functional electrical muscle stimulation. An ultrasound examination of the lower extremities was conducted twice a week on each patient until completion of the study (28 days or discharge, whichever came first). Electrical muscle stimulation was discontinued after 4 mo of the study because of discomfort, blister formation and high drop-out rate. Ten patients developed DVT during the study period. In 17 of the 32 cases of DVT, venography was performed, which confirmed the ultrasound findings in every case. The 32 cases of DVT differed from those without DVT by having a higher prevalence of hypertension (P = 0.02), cholesterol (P = 0.08) and a longer time interval between stroke and admission (P less than 0.05). We conclude that ultrasound is effective for DVT detection in the rehabilitation setting, and two-thirds of such cases are detectable on admission. PMID- 1742003 TI - Statistical conclusion validity. Multiple inferences in rehabilitation research. AB - The problem of multiple statistical inferences and Type I error rates in rehabilitation research is examined. The Bonferroni method is the most commonly advocated procedure to control Type I error in clinical research. The traditional Bonferroni method is often overly conservative and results in a loss of statistical power when more than a small number of comparisons are evaluated. Adjustments to the Bonferroni method designed to control or reduce the incidence of Type I errors and improve the statistical conclusion validity of rehabilitation research are presented. The adjusted or sharpened Bonferroni methods allow the researcher to control the incidence of Type I errors while maintaining statistical power. Adjustments to the Bonferroni method are simple to compute and applicable to a wide variety of statistical tests. The use of appropriate multiple comparison procedures will reduce the number of Type I errors and improve the statistical conclusion validity of rehabilitation research studies. PMID- 1742004 TI - Orthopedic surgery and rehabilitation for the prolongation of brace-free ambulation of patients with Duchenne muscular dystrophy. AB - The purpose of this study was to prospectively evaluate the results of a short comprehensive program involving early lower extremity musculotendinous surgery followed by a definitive course of rehabilitation on contractures and the duration of ambulation for patients with Duchenne muscular dystrophy. Seven patients were treated while ambulating with little difficulty and six were treated just before or after becoming wheelchair-dependent. Predicted post treatment duration of ambulation was calculated from established clinical criteria. Actual prolongation of brace-free ambulation after treatment was a mean of 0.8 yr greater than predicted for the group as a whole but 0.93 yr for the group treated early by comparison with 0.63 yr for those treated according to the customary approach. The number of falls significantly decreased from 84 +/- 87 to 1 +/- 1 per month postoperatively (P less than 0.05); however, the speed of ambulation over a distance of 10 yards decreased from 10.2 +/- 4 s to 12.1 +/- 7.3 s. Three patients who had tibialis posterior transfers retained antigravity plus dorsiflexor strength and continue to wear normal footwear 2.5, 3.7 and 4.0 yr after loss of ambulation. We conclude that ambulation becomes more stable and brace-free ambulation may be prolonged by a comprehensive program of early orthopedic surgery and rehabilitation. Earlier intervention is also better tolerated. PMID- 1742005 TI - Asthmatic amyotrophy. Three cases. AB - Asthmatic amyotrophy is becoming a well established clinical phenomenon. A polio like syndrome, it is characterized by an asymmetrical lower motor neuron paralysis after an acute asthmatic episode. We are presenting three additional cases of this syndrome to add to the literature describing this phenomenon. Our cases are similar to the 18 previously reported cases showing an asymmetrical flaccid paralysis accompanied by normal sensation. The prognosis for full recovery of function is poor. Anterior horn cell damage is postulated because no sensory loss has been found in any patients. PMID- 1742006 TI - Medical economics for PM&R. II. Current financial trends and the future of PM&R. PMID- 1742007 TI - Physical parameters and speed of wheeling associated with two specific wheelchairs by individuals with spinal cord function. PMID- 1742008 TI - The new stereological methods for interpreting functional morphology from slices of cells and organs. PMID- 1742009 TI - Agonist-induced fluctuations in cytoplasmic calcium in primary cultures of bovine endothelial cells. AB - Endothelial cells play an important role in the vascular responsiveness to many stimuli by releasing locally active agents. The intracellular signal which links the external stimulus to the release of the active compounds is almost certainly an elevation in cytoplasmic calcium (Cai2+). Thus a detailed knowledge of Cai2+ regulation is central to an understanding of the physiology and pharmacology of endothelial cells. The present experiments, on single bovine aortic endothelial cells, demonstrate that agonists stimulate complex changes in Cai2+. These include rapid and regular fluctuations in Cai2+ which are different from the oscillations reported in other endothelial cells and non-excitable cells. The fluctuations are completely abolished in media containing low calcium, 2 mM cobalt or caffeine but are not affected if the cells are bathed in isotonic potassium solutions. The hypothesis is put forward that the fluctuations in Cai2+ are associated with localized influxes of calcium and are possibly involved with the recycling of calcium between the internal stores, the cytoplasm and the external medium. PMID- 1742010 TI - Outward currents in rabbit pulmonary artery cells dissociated with a new technique. AB - Single cells from the rabbit pulmonary artery were isolated using a new and convenient procedure. Strips of muscle were incubated overnight in papain at 6 degrees C and dispersed the following morning after warming the tissue for 10 min. This method consistently produced a high yield of relaxed cells, which reversibly responded to vasoconstrictors and remained viable for many hours. The electrophysiological properties of these cells were studied using the patch-clamp technique in the whole-cell configuration. In physiological Ca2+ solution with K(+)-filled pipettes, cells had a high input resistance (approximately 17 G omega) and an average resting potential of -55 mV. In voltage clamp, several components of outward current could be identified. Depolarizing voltage steps revealed a prominent, transient current (Itran), having extremely rapid activation (less than 5 ms) and inactivation (less than 15 ms) kinetics. Itran was followed by a more slowly activating current (IKso) that was sustained over 100 ms. Both currents were essentially abolished by a 4-aminopyridine (4-AP) and sensitive to Ca2+ influx. IKso, but not Itran, was blocked by tetraethylammonium (TEA) and had the properties of a Ca(2+)-activated K+ current. Holding the membrane potential at -40 mV completely inactivated Itran and unmasked a time independent, background current superimposed on IKso. The background current was also blocked by 4-AP. In addition, when adenosine triphosphate (ATP), but not guanosine triphosphate (GTP), was omitted from the patch-pipette, spontaneous bursts of outward current (SOCs) were superimposed on the voltage-activated currents. However, since SOCs were rarely observed when ATP and GTP were present together, they are unlikely to be active under physiological conditions. Thus at least four types of outward current can be distinguished in isolated rabbit pulmonary artery cells. These include a novel transient current which could be activated from the resting potential. It activates much more rapidly than outward currents previously reported in vascular muscle, and would rapidly oppose action potential firing. This current could therefore be responsible for the inability of large elastic arteries to fire action potentials. PMID- 1742011 TI - Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver. AB - The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I-tyramine cellobiose (125I-TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I-TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered. The skin at the injection site contained 47%, the popliteal gland at the side of injection 10%, and the liver 8% of the injected dose. At 48 h the three organs contained 40% of the injected dose with 17% in the skin, 10% in the lymph node and 13% in the liver. The decline in recovery could be accounted for by urinary excretion of the tracer, implying that some tracer had been released from the cells after endocytosis. Chromatography revealed that over 85% of 125I-TC-hyaluronan in the lymph nodes and liver was of low molecular mass throughout the experiment. In skin, 4% of the injected tracer was recovered with low molecular mass at 6 h, increasing to 12% of injected dose at 24 and 48 h. Thus, a minimum of 12% of the injected tracer was catabolized per 24 h at the skin injection site. If cells in skin are responsible for the subsequent release of tracer, as seen from the decrease in recovery of the injected dose, another 10-15% of the tracer could have been catabolized locally in the skin per day. The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver. PMID- 1742012 TI - Action potential duration and the inotropic response to reduced extracellular potassium in guinea-pig ventricular myocytes. AB - The mechanism of the inotropic effect of a reduction of extracellular potassium from 5.4 to 2.7 mM was investigated in myocytes isolated from guinea-pig ventricle. Action potentials were recorded using intracellular microelectrodes and cell shortening was measured by analysis of a video image. Changes in cytosolic calcium transients were estimated from calcium-activated currents under voltage-clamp conditions. The aim was to determine whether the prolongation of action potential duration which was observed to occur in low potassium might contribute to the increased shortening and increase in calcium-activated current under these conditions. Using a voltage-clamp waveform to mimic the waveform of the action potential, it was found that reduction of potassium caused a marked increase in cell shortening and of calcium-activated current in the absence of prolongation of the 'action potential' waveform. No change in inward calcium current was detected when extracellular potassium was reduced. The sensitivity to strophanthidin appeared to be increased under these conditions. We conclude that prolongation of the action potential is not a major factor contributing to the increased cell shortening and to the increased cytosolic calcium transient when extracellular potassium is reduced. PMID- 1742013 TI - Avian lower intestine adapts to dietary salt (NaCl) depletion by increasing transepithelial sodium transport and microvillous membrane surface area. AB - A tissue sampling scheme for tandem assessments of whole-organ physiology and ultrastructure was applied to the lower intestine (coprodaeum) of White Plymouth Rock hens on low- and high-NaCl diets. The objective was to correlate net amiloride-sensitive Na transport determined using the Ussing chamber with the plasma membrane surface areas due to microvilli at the epithelial cell apex. Hens kept on the low-NaCl diet for 3-4 weeks displayed a substantial increase in short circuit current and in total microvillous membrane surface area. The latter rose from a group mean +/- S.E.M. of about 90 +/- 9.7 cm2 to one of 200 +/- 38 cm2 per organ. An increase in epithelial cell membrane contributed to, but did not fully explain, the increase in microvillous area. No differences in mean cell height or mean cell volume were found but the average cell in the low-NaCl birds was better developed in possessing a greater surface area of microvilli. On the high-NaCl diet, the epithelium was 33 +/- 2.7 microns tall and contained about 270 +/- 15 million cells. Each cell had a volume, on average, of 540 +/- 59 microns 3 and a microvillous surface of 32 +/- 2.6 microns 2. After NaCl depletion, there were 420 +/- 75 million cells and the average microvillous surface was 49 +/- 5.3 microns 2 per cell. The morphological adaptations alone do not explain the increased net Na transport found on the low-NaCl diet. Of cardinal importance is greater density of open Na channels in apical cell membranes. PMID- 1742014 TI - Regulation of cellular water and ionic content in lungs of fetal and adult rats. AB - Slices of lungs from late-fetal (1 day pre-partum) and adult rats lost K+ and gained Na+, Cl-, water and Ca2+ during pre-incubation at 1 degrees C. These changes were reversed upon restoration to 37 degrees C. The recovery of composition at 37 degrees C was completely dependent on cell respiration in adult slices; by contrast, glycolysis could support partial recovery in the fetal slices. Ouabain completely inhibited K+ reaccumulation at both ages but inhibited net extrusion of water by no more than 50%. Replacement of medium Cl- with NO3- prevented the extrusion of water in the presence of ouabain in adult but not fetal slices. Transmission electron microscopy of type II epithelial cells in slices of both ages showed that ouabain induced the formation of many cytoplasmic vesicles, apparently derived from the Golgi apparatus. Regulation of cell ionic and water content is thus generally similar in late-fetal and adult lung tissue, but there are differences in the source of ATP and in some features of ouabain resistant volume regulation. PMID- 1742015 TI - The effect of level of contraction on the electromyographic power spectrum of the diaphragm in pigs. AB - We investigated the relationship between the frequency components of myoelectric power spectra of the diaphragm and the level of diaphragmatic contraction in seven anaesthetized spontaneously breathing pigs. Electromyographic activity of the costal and crural portions of the diaphragm were recorded with fish-hook electrodes and the frequency-power spectra during inspiration were computed and expressed in terms of centroid frequency (fc). Diaphragmatic force was indirectly assessed as transdiaphragmatic pressure (Pdi) which was measured with balloon catheter systems placed in the abdomen and oesophagus. The relationships between Pdi and costal and crural fc were assessed during brief (2 min) and incremental increases in diaphragmatic contraction, achieved by gradual occlusion of the inspiratory line of the breathing circuit. When Pdi was increased to 128, 191, 287 and 421% of the value measured during unobstructed breathing, costal and crural fc rose significantly in all animals because of an increase in the power of high-frequency components and a decline in the power of low-frequency components. Both costal and crural fc returned to control values within 5 min of the release of inspiratory occlusion. Our results indicate that the level of contraction is an important determinant of the diaphragmatic myoelectric power spectrum and should be taken into consideration when using power spectral analysis to diagnose diaphragmatic mechanical failure. PMID- 1742016 TI - A study of the action of angiotensin II on perfusion through the cortex and papilla of the rat kidney. AB - The effect of angiotensin II on blood pressure and perfusion of blood through the cortex and papilla regions of the kidney was determined in pentobarbitone anaesthetized rats which were subjected to laser-Doppler flowmetry to estimate regional renal haemodynamics. Angiotensin II was infused at 10, 45 and 150 ng (kg body weight-1 min-1) which caused dose-related increases in blood pressure of 3, 12 and 24%, respectively, and decreases in cortical perfusion of 9, 15 and 24%, respectively. Papillary perfusion did not change at any dose of angiotensin II. This pattern and magnitude of responses to angiotensin II in blood pressure, cortical and papillary perfusions was essentially unaffected (a) following blockade of cyclo-oxygenase activity with indomethacin (1.3 mg kg-1 plus 2 mg kg 1 h-1), (b) during infusion of a bradykinin antagonist, at 1.3 micrograms min-1, (c) when renal perfusion pressure was regulated at control levels and (d) following Methylene Blue administration to inhibit potential endothelial-derived relaxing factor production. By contrast, infusion of phenylephrine at 5, 10 and 20 micrograms kg-1 min-1 caused dose-related increases in blood pressure and decreases in both cortical and papillary perfusions reaching some 28, 7 and 17% respectively at the highest dose of phenylephrine used. These results showed that both cortex and papilla were sensitive to vasoconstrictor agents. They are compatible with the suggestion that angiotensin II regulates cortical but not papillary perfusion in the kidney, and that these responses do not depend on prostaglandin, bradykinin, renal perfusion pressure or endothelium-derived relaxing factor. PMID- 1742017 TI - Arteriolar vasodilatation in frog skeletal muscle in vivo: modification of second messenger systems. AB - This study was concerned with the role of cyclic nucleotides in the post junctional vasodilatation mechanism. Interventions with second messenger systems involving cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), allowed the role of these nucleotides in vascular smooth muscle to be evaluated in the autoperfused, transparent frog muscle, m. cutaneous pectoris. The microcirculation was observed by intravital microscopy, and arteriolar diameters were continuously recorded. Pre- and post-junctional effects were distinguished by comparing results in control frogs with those obtained in frogs that had been chemically sympathectomized with either 6 hydroxydopamine or tetrodotoxin. Arterioles that were pre-contracted with adrenaline dilated in response to topical application of forskolin or sodium nitroprusside, which are direct activators of intracellular adenylate cyclase and guanylate cyclase, respectively. Arterioles were also dilated by 3-isobutyl-1 methylxanthine (IBMX), which is a non-selective inhibitor of cyclic AMP- and cyclic GMP-phosphodiesterase, and by rolipram, which is a selective inhibitor of the calcium-independent cyclic AMP-phosphodiesterase. Dibutyryl-cyclic AMP and dibutyryl-cyclic GMP also caused vasodilatation. These results indicate that in vascular smooth muscle, intracellular mechanisms involving cyclic nucleotides (cyclic AMP and cyclic GMP) are important in vasodilatation. They may act in conjunction with pre-junctional inhibitory mechanisms on sympathetic nerves. PMID- 1742018 TI - Inhibition of Ca2+ mobilization by caffeine in a cultured vascular smooth muscle cell line (A7r5). AB - The effects of caffeine on the resting level and agonist-induced changes in intracellular calcium ([Ca2+]i) have been studied in the vascular smooth muscle cell line A7r5. Caffeine (1-30 mM) lowers the resting [Ca2+]i by reducing the entry of Ca2+ and inhibits completely the mobilization of Ca2+ by arginine vasopressin. Application of forskolin, to elevate cAMP, does not affect the resting level of Ca2+i but does abolish the agonist-induced rise. These data add to the complexity of caffeine-induced changes in [Ca2+]i and point to a possible interaction between cAMP and other second messenger systems mobilizing Ca2+i in this cell type. PMID- 1742019 TI - Intracellular pH and buffering power measured in isolated single cells from pregnant rat uterus. AB - Intracellular pH (pHi) affects smooth muscle function yet there have been few direct pHi measurements. Using the fluorescent indicator, 2',7'-bis-2 (carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester, we report here the first measurements of pHi and buffering power (beta) in single, isolated, uterine smooth muscle cells. Mean pHi in cells from pregnant rat uteri was 7.09 +/- 0.08 (+/- S.E.M., n = 16 cells; 37 degrees C), and beta was found to be 12.8 +/- 2.8 mmol/l per pH unit (n = 15). The cells were able to regulate their pHi in the presence of butyrate when perfused in nominally CO2-free solution. PMID- 1742020 TI - BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. AB - In recent years, nerve growth factor (NGF) has gained attention as a potential therapeutic agent for Alzheimer's disease (AD). To study the expression of NGF and its homologs, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT 3), postmortem samples of hippocampus from AD and control donors were examined by in situ hybridization. Hybridization signal for BDNF, but not NGF or NT-3, was decreased in samples of hippocampus from donors with AD. Decreased transcript abundance of BDNF mRNA in hippocampi of individuals with AD was verified by an RNAase protection assay. These results suggest the possibility that decreased expression of BDNF may contribute to the progression of cell death in AD. PMID- 1742021 TI - The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice. AB - Dopamine beta-hydroxylase (DBH) catalyzes the final step in the biosynthesis of norepinephrine, the principal classic neurotransmitter of peripheral sympathetic neurons. We have shown that 5.8 kb of 5' upstream region from a cloned human DBH gene promoter is sufficient to direct expression of the E. coli lacZ gene in transgenic mice to neurons of the locus ceruleus and other classic noradrenergic brain stem nuclei, sympathetic ganglion neurons, and adrenal chromaffin cells. lacZ expression was also observed in neurons of the enteric system, the retina, some sensory and all cranial parasympathetic ganglia, and some diencephalic and telencephalic brain nuclei. The expression pattern of the transgene in DBH immunonegative sites overlapped with many sites where expression of tyrosine hydroxylase or phenylethanolamine N-methyltransferase, two other catecholamine biosynthetic enzymes, has been reported. PMID- 1742022 TI - Some neuronal cell populations express human dopamine beta-hydroxylase-lacZ transgenes transiently during embryonic development. AB - The 5' flanking region from the human dopamine beta-hydroxylase gene directs expression of bacterial beta-galactosidase reporter genes to a subset of adult neurons and adrenal chromaffin cells of transgenic mice. In this paper, we examine the spatial and temporal patterns of expression of these transgenes during embryogenesis. Expression begins at embryonic day 9 in the developing central and peripheral nervous systems and persists in cell populations in which expression is observed in adult transgenic mice. However, transient embryonic expression occurs in presumptive neuroblasts in developing sensory ganglia and ventrolateral neural tube that are destined to synthesize neurotransmitters other than catecholamines. These observations support the concept that some cells fated to become "non-catecholaminergic" neurons exhibit transient catecholaminergic features during their differentiation. PMID- 1742023 TI - The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker. AB - Following voltage-dependent activation, Drosophila Shaker K+ channels enter a nonconducting, inactivated state. This process has been proposed to occur by a "ball-and-chain" mechanism, in which the N-terminus of the protein behaves like a blocker tethered to the cytoplasmic side of the channel and directly occludes the pore to cause inactivation. To complement the ample evidence for the involvement of the N-terminus, we sought evidence that it blocks the pore directly. We found that inactivation exhibits several distinctive properties of pore blockade. First, recovery was speeded by increased external K+ concentrations, just as blockade can be relieved by trans-permeant ions. Second, single-channel experiments show that the channel reopens from the inactivated state upon repolarization. These openings were usually required for recovery, as though the blocking particle must exit the pore before the channel can close. PMID- 1742024 TI - Shaker, Shal, Shab, and Shaw express independent K+ current systems. AB - Although many K+ channel genes encoding homologous subunits have been cloned, a central question remains: how do these subunits associate to produce the diversity of K+ currents observed in living cells? Previous work has shown that different subunits encoded by the Shaker gene subfamily are able to form heteromultimers, which add to the diversity of currents. However, the unrestrained mixing of subunits from all genes to form hybrid channels would be undesirable for some cells that clearly require functionally discrete K+ currents. We show that Drosophila Shaker, Shal, Shab, and Shaw subunits form functional homomultimers, but that a molecular barrier to heteropolymerization is present. Coexpression of all four K+ channel systems does not alter their individual properties in any way. These experiments also demonstrate that multiple, independent A-current systems together with multiple, independent delayed rectifier systems can coexist in single cells. PMID- 1742025 TI - Calcium-induced release of calcium regulates differentiation of cultured spinal neurons. AB - Voltage-dependent calcium influx has been shown to regulate the differentiation of cultured amphibian spinal neurons. We have examined the transient elevation of intracellular calcium induced by depolarization, using calcium indicators and confocal microscopy with high temporal and spatial resolution. Rapid calcium elevations in both the nucleus and the cytosol are primarily due to calcium dependent release of calcium from intracellular stores. Depletion of stores associated with the endoplasmic reticulum reduces all transients. Elevations diminish with neuronal maturation. Depletion of stores of intracellular calcium at early times affects neuronal differentiation in a manner similar to the prevention of influx. The results indicate that both influx and release are necessary to promote neuronal differentiation. PMID- 1742026 TI - Role of calcium and protein kinase C in development of the delayed rectifier potassium current in Xenopus spinal neurons. AB - The delayed rectifier current of embryonic Xenopus spinal neurons plays the central role in developmental conversion of calcium-dependent action potentials to sodium-dependent spikes. During its maturation, this potassium current undergoes a pronounced increase in rate of activation. The mechanism underlying the change in kinetics was analyzed with whole-cell voltage clamp of neurons cultured under various conditions. Calcium is necessary at an early stage of development, to permit influx that triggers subsequent release of calcium from intracellular stores. Its action is prevented by depletion of protein kinase C and mimicked by stimulation of the kinase. Calcium influx through voltage dependent channels at early stages of development regulates the differentiation of potassium current kinetics and modulation of the ionic dependence of action potentials. PMID- 1742027 TI - The duration of neurotrophic factor independence in early sensory neurons is matched to the time course of target field innervation. AB - To investigate how the onset of neurotrophic factor dependence in neurons is coordinated with the arrival of their axons in the target field, we have studied the survival of four populations of cranial sensory neurons whose axons reach their common central target field, the hindbrain, at different times. We show that neurons whose axons reach the hindbrain first survive for a short time in culture before responding to brain-derived neurotrophic factor (BDNF). Neurons whose axons reach the hindbrain later survive longer before responding to BDNF. These differences in survival, which arise prior to gangliogenesis, may play a role in coordinating trophic interactions for cranial sensory neurons. PMID- 1742028 TI - Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. AB - In vertebrates, the formation and maintenance of neuronal connections are subject to regulation by multiple target-derived, diffusible (neurotrophic) factors. Here we describe the identification and characterization of a novel neurotrophic factor designated neurotrophin-5 (NT-5). NT-5 is structurally related to nerve growth factor and is expressed in embryonic as well as adult tissues. Recombinant NT-5 promotes the survival of peripheral sensory and sympathetic neurons and induces differentiation of the pheochromocytoma cell line PC12. NT-5 activates two trk-related tyrosine kinase receptors and shares these receptors with other neurotrophins. Activation of multiple receptors may permit a single neurotrophin to control target innervation by distinct neuronal populations. Receptor sharing could enable neurotrophic factors emanating from distinct targets to cooperate in regulating neurons with multiple connections. PMID- 1742029 TI - Color Doppler echocardiographic assessment of atrial septal defect size: correlation with surgical measurements. AB - In patients with atrial septal defect (ASD), color flow Doppler echocardiography provides visualization of the transseptal jet, the maximal dimension of which can be assumed to correspond to the maximal dimension of the true orifice. To test whether color flow Doppler echocardiography can provide an alternative method for measurement of ASD size, we studied 63 consecutive patients with echocardiographic evidence of ASD. In 48 patients the maximal dimension of the jet was measured in the parasternal, apical, or subcostal four-chamber view or in the parasternal short-axis view. In the remaining 15 patients transesophageal echocardiography was performed because of transthoracic views were inadequate. The transesophageal studies also measured, from two-dimensional images, the maximal transverse discontinuity in the atrial septum. All patients underwent surgical repair, during which the surgeon directly measured the maximal dimension of ASD. Linear regression equations were performed to compare transthoracic and transesophageal dimensions to those measured at operation. Correlation coefficients were as follows for transthoracic versus surgical measurements: r = 0.745, standard error = 4.35, p less than 0.001. Transesophageal measurements derived from both two-dimensional images and echocardiographic jet width showed similar excellent correlation with surgical measurements (n = 0.91, standard error = 4.33, p less than 0.001; and r = 0.919, standard error = 4.42, p less than 0.001, respectively). We conclude that ASD size derived from color flow Doppler echocardiography shows a good correlation with the anatomic maximal dimension observed at operation. Both transesophageal color flow Doppler echocardiography of jet width and direct surgical measurement of the defect provide an accurate estimation of ASD size. PMID- 1742030 TI - Left atrial appendage dysfunction: a cause of thrombosis? Evidence by transesophageal echocardiography-Doppler studies. AB - The blood flow velocity patterns within the left atrial appendage were studied by transesophageal color flow imaging and pulsed Doppler in 84 patients. At the time of the study, 57 of the patients were in sinus rhythm, 25 were in atrial fibrillation, and two were in atrial flutter. The relationships between atrial rhythm, blood flow pattern and the presence/absence of spontaneous echocardiographic contrast or thrombus within the appendage were investigated. Transesophageal echocardiography allowed recording of blood flow velocities in 81 of the 84 patients studied. In 51 of the 55 patients in sinus rhythm the pulsed Doppler study showed a biphasic blood flow pattern, whereas a multiphasic pattern was found in the two patients with atrial flutter and in 14 patients with atrial fibrillation. In four patients with sinus rhythm and 10 patients with atrial fibrillation, no significant blood flow velocity could be detected. Thrombus or spontaneous echocardiographic contrast were found within the left atrial appendage in 20 patients, and in all these patients blood flow was either absent or significantly reduced. Our findings indicate that an absent or low blood flow velocity within the left atrial appendage represents a predisposing factor for thrombosis. Isolated left atrial appendage dysfunction has been documented in four patients during sinus rhythm, which may lead to thrombosis. This observation may offer an explanation for cardioembolic events that occur occasionally in patients without apparent heart disease and sinus rhythm. PMID- 1742031 TI - Long-term reproducibility of conventional Doppler analysis in patients with prosthetic valves. AB - Long-term reproducibility of Doppler recordings made by the same investigator using the same ultrasound equipment was determined in 50 clinically stable patients. The mean interval between the first and second examination was 16 +/- 7 months. In 90% of the 33 patients with aortic prostheses, the relative difference between the first and second examination was less than 16% (mean value 9.1%) for the maximum instantaneous gradient and less than 17% (mean value 7.4%) for the mean gradient; the relative difference was less than 20% (mean value 8.5%) for the maximum flow velocity in the left ventricular outflow tract and less than 24% (mean value 10.8) for the maximum flow velocity ratio. In 90% of the 25 patients with mitral prostheses, the absolute difference between the first and second examination was less than 3 mmHg for the maximum instantaneous gradient, less than 2.5 mmHg for the mean gradient, and less than 20 msec for the pressure half time. We conclude that long-term reproducibility of Doppler echocardiographic characteristics of prosthetic valve function is good as far as transprosthetic gradients or pressure half-time are concerned but is less so for maximum flow velocity in the left ventricular outflow tract and the maximum flow velocity ratio. Changes beyond the aforementioned values may represent a real change in prosthetic valve function. PMID- 1742032 TI - Effect of sample volume location on Doppler-derived transmitral inflow velocity values. AB - In 25 patients with acute myocardial infarction and in 25 normal subjects, pulsed wave Doppler echocardiography was performed in the apical four-chamber view with the sample volume first between the mitral leaflet tips and then at the mitral anulus. The early filing wave (E) and late filling wave (A) peak velocities measured from Doppler strip charts were significantly (p less than 0.001) higher at the tips in both groups. E velocity increase was greater than A velocity increase, producing a significantly (p less than 0.001) higher E/A velocity ratio at the tips than at the anulus. The deceleration time was longer at the tips than at the anulus (p less than 0.001) in both groups. Therefore it is important to know sample volume location in the interpretation of mitral inflow velocity. It is critical to maintain the same sample volume location in serial assessments of left ventricular diastolic filling characteristics. PMID- 1742033 TI - Transesophageal echo-Doppler echocardiographic assessment of pulmonary venous flow patterns. AB - Fifty-eight of 61 consecutive patients undergoing transesophageal echo-Doppler echocardiography provided excellent signals to permit assessment of pulmonary venous blood low patterns. Normal antegrade pulmonary venous flow during ventricular systole was biphasic and was characterized by a short, low velocity (28 +/- 17 cm/sec), early systolic jet (P1), and longer, higher velocity (41 +/- 23 cm/sec), late systolic jet (P2). Antegrade pulmonary venous flow during ventricular diastole (P3) was of moderate velocity (34 +/- 17 cm/sec) and was monophasic; during atrial contraction there was transient, low velocity (-17 +/- 11 cm/sec) and reversal of flow (P4). The early systolic antegrade venous flow (P1) was absent or reversed in rhythm disorders, which interrupted normal synchronized atrioventricular activation. These rhythm disorders also were associated with diminished peak flow velocities during late systole (P2). Abnormalities in systolic left ventricular function and mitral regurgitation also had this effect. Diastolic flow velocities (P3) remained constant, except in patients with mitral regurgitation. In these patients diastolic peak flows were significantly increased above normal. In cases of atrial fibrillation or ventricular pacing the late diastolic reversal of flow resulting from atrial contraction (P4) was absent. CONCLUSIONS: Transesophageal echo-Doppler echocardiography gives high quality signals of pulmonary venous inflow to help assess function of the left ventricle and left atrium. Multiple factors affect the patterns. This study suggests caution in the interpretation of abnormal patterns, particularly of reduced systolic pulmonary vein flow in the presence of left ventricular dysfunction, atrial fibrillation, ventricular pacing, and mitral regurgitation. PMID- 1742034 TI - Prediction of rapid versus prolonged healing of infective endocarditis by monitoring vegetation size. AB - The diagnostic value of transesophageal echocardiography in monitoring the clinical course has been evaluated in 83 patients with echocardiographic evidence of infective endocarditis. A total of 103 vegetations attached to the aortic or mitral valves were detected by use of the transesophageal approach. The patients were monitored for a mean of 74 weeks and underwent a minimum of two consecutive transesophageal echocardiographic examinations. Group A included patients with increasing or remaining constant size of vegetation (8.2 +/- 1.5 to 11.2 mm, p less than 0.05) during 4 to 8 weeks of antimicrobial therapy, whereas group B was formed by patients with decreasing vegetation size (8.3 +/- 0.8 to 4.9 +/- 0.8 mm, p less than 0.05). The incidences of complications after diagnosis and onset of therapy was higher in group A than in group B: valve replacement (45% versus 2%, p less than 0.05), embolic events (45% versus 17%, p less than 0.05), perivalvular abscess formation (13% versus 2%, p less than 0.05), and mortality (10% versus 0%, respectively, p less than 0.05). Staphylococcus aureus was the most frequent organism isolated in group A (44% versus 11% in B, p less than 0.05) and Streptococcus viridans in group B (33% versus 18% in A, p less than 0.05). Blood cultures were negative in nearly 50% of the patients in each group. There was no difference in the incidences of complications in patients with positive or negative blood cultures. We conclude that an increase in vegetation size during antibiotic therapy predicts a prolonged healing phase of infective endocarditis. This prolonged healing period is associated with a significantly increased risk of complications, independent of blood culture results. Monitoring vegetation size contributes important information concerning prognosis and stage of risk, and it aids in the choice of patient management in infective endocarditis. Because embolic events after diagnosis and onset of treatment are less frequent in rapid-healing endocarditis, surgery cannot be recommended to prevent further events taking into account the high risk of surgery. PMID- 1742035 TI - Accuracy of three-dimensional volume measurement using biplane transesophageal echocardiographic probe: in vitro experiment. AB - Two phased-array scanning methods can be used for volumetric transesophageal echocardiographic imaging: (1) pull-back "breadloaf" reconstruction, and (2) rotation "fan-like" reconstruction. The purpose of this study was to (1) test accuracy and precision of pull-back versus rotational geometries for three dimensional volume determination, and (2) test accuracy of the resulting surface/volume rendered images. The endoscope shaft was inserted into a tube with the handle connected to a stepper device. Seventeen balloons (61 to 471 ml) were put into a water bath consecutively. Two scans were performed: (1) pull-back: the probe was withdraw in 1 mm steps to obtain parallel "breadloaf" slices, and (2) rotational: the probe was rotated in increments of 1.8 degrees, 3.6 degrees, or 5.4 degrees to obtain "fan-like" slices. Each image was digitized for computer analysis. The data were interpolated into 128 x 128 x 128 voxels for three dimensional reconstruction. Volume measurement was done using a stereometric random marking method. Volumes obtained from the reconstructed images were compared with the true volume (weight) by linear regression analysis. Excellent correlation between measured and actual volumes was obtained from rotation scans as follows: for 1.8 degrees steps (r = 0.9987, SEE = 6.5 ml), for 3.6 degrees steps (r = 0.9959, SEE = 11.5 ml), and for 5.4 degrees steps (r = 0.9943, SEE = 13.5 ml). The pull-back scans showed r = 0.9990, SEE = 5.8 ml. Three-dimensional surface/volume rendered images of the balloons indicate that 1.8 degrees rotation scans are almost as good as 1 mm pull-back scans. We conclude that volume measurements from rotation scans in vivo will not be hindered by scan geometry or software interpolation. PMID- 1742036 TI - Unruptured noncoronary sinus of Valsalva aneurysm: preoperative characterization by transesophageal echocardiography. AB - We describe a patient with a large unruptured sinus of Valsalva aneurysm that was discovered incidentally. Transesophageal echocardiography was used to characterize the aneurysm preoperatively, and was helpful intraoperatively in assessment of the degree of native aortic valvular regurgitation after repair. The use of transthoracic echocardiography, contrast echocardiography, Doppler echocardiography, and transesophageal echocardiography are discussed in this condition. PMID- 1742037 TI - Echocardiographic diagnosis of left ventricular pseudoaneurysm in a child after cardiopulmonary bypass. PMID- 1742038 TI - Multifaceted echocardiographic approach to the diagnosis of a ruptured sinus of Valsalva aneurysm. PMID- 1742039 TI - Pseudoaneurysm of the aortic root diagnosed by noninvasive imaging: report of a case. AB - Pseudoaneurysm of the aortic root is a rare condition typically diagnosed by the use of cardiac catheterization and aortography or by surgical exploration. This case describes a patient who was shown to have a pseudoaneurysm of the aortic root without evidence of any acquired etiologic factors other than atherosclerotic vascular disease. Two new advanced techniques of noninvasive imaging were used in confirming the diagnosis: transesophageal echocardiography and gated magnetic resonance imaging. This case highlights the value of techniques such as these to reliably assess the heart and great vessels without the need for more invasive procedures. PMID- 1742040 TI - Doppler flow velocity patterns of the superior vena cava, inferior vena cava, hepatic vein, coronary sinus, and atrial septal defect: a guide for the echocardiographer. AB - Pulsed-wave Doppler provides the echocardiographer the advantage of range resolution; confusion as to the source of Doppler shift information is unusual. One area of the heart that may lead to interpretive difficulties, however, is the right atrium because the right atrium receives blood flow from three venous sources and from the left atrium when an atrial septal defect is present. Our article presents information on the normal pulsed-wave Doppler spectral displays for the superior vena cava, inferior vena cava, hepatic vein, and coronary sinus. Because it is clinically pertinent, methods on how to differentiate these normal venous flow patterns from atrial septal defect flow will be emphasized. PMID- 1742041 TI - Transesophageal echocardiography: a sonographer's perspective. AB - Clinical transesophageal echocardiography is increasingly being applied for the evaluation of numerous functional and anatomic cardiac abnormalities. This new technology has opened an area of invasive ultrasonography that has changed and expanded the role of the cardiac sonographer. The sonographer is essential for the implementation and performance of this recent advance in echocardiography. PMID- 1742042 TI - Cardiac embryology: basic review and clinical correlations. PMID- 1742043 TI - Whistling face syndrome. A case report and literature review. AB - The cranio-carpo-tarsal or "whistling face" syndrome was first described by Freeman and Sheldon in 1938. More than 60 cases with great variability of expression are known till now and autosomal dominant as well as recessive inheritance and sporadic cases suggest a genetic heterogeneity. We review 60 well documented cases of the literature and present a patient with a severe form, who died of bronchopneumonia at the age of 9 months. The facial stigmata of his mother and the ulnar deviations of his maternal grandfather support the autosomal inheritance of the syndrome. PMID- 1742044 TI - Congenital hyperammonemia: symptomatic carrier girl patient and her asymptomatic heterozygous mother for ornithine transcarbamylase (OTC) deficiency: specific enzyme diagnostic and kinetic investigations for the detection of heterozygous genostatus. AB - Activities of the specific enzymes of the inherited hyperammonemic syndromes (carbamoyl-phosphate synthetase CPS), ornithine transcarbamylase (OTC), arginine succinate-synthetase (ASS), arginine-succinate-lyase (ASL) and arginase (ASE) were measured in a liver biopsy specimen of a 2 years-old girl suffering from chronic hyperammonemia and in the erythrocyte- and leukocyte-homogenisate of her parents. The activity of OTC in liver homogenisate of the patient was 62.9 percent; in the leukocytes of the parents it was 78.5 percent (in mother) and 102 per cent (in the father) as compared to the controls. Our patient proved to be a symptomatic carrier of OTC deficiency and her mother proved to be an asymptomatic carrier. PMID- 1742045 TI - High consanguinity rate in Hungarian gipsy communities. AB - Reproductive data of 1074 gipsy women between 13 and 52 years with one or more children were obtained by gipsy social workers through anonymous personal interview confirmed by available official documents. Socioeconomic status of five different gipsy communities studied is much lower than the Hungarian average. Their reproductive activity is also different, e.g., first births occur in much younger age. The high endogamy was proved by the gipsy origin of male partners in 90% of couples. The occurrence of first cousin couples was 16 times higher than that of the Hungarian population at large, however, its range was wide from 0% to 21% in different regions studied. PMID- 1742046 TI - Hyperlipemia and hyperlipoproteinemia [HLP] screening among the children from premature myocardial infarction risk families. AB - Serum lipids and lipoproteins were investigated in the premature myocardial infarction (PMI) risk families before 45 years of age with the aid of screening for hyperlipemia and hyperlipoproteinemia (HLP): in the case of 174 persons from Csongrad County from the Departments of Internal Medicine I and II and of 42 patients (fathers) suffering from PMI and their 79 "high risk" children from Heves County. In the investigated three groups of "high risk" children the genetically determined antiatherogenic HDL-Ch level diminished in 34.8, 52.3, 40.5 per cent. Significant negative correlation was detected between the serum HDL-Ch and beta-lipoprotein; significant positive correlations were found between the HDL-Ch and the serum lipase activity; between the beta-lipoprotein and the phospholipid level; significant negative correlation was proved between the HDL Ch and the phospholipid level in the group of PMI patients and their offsprings. The Ch/Tg, and the HDL-Ch ratios were significantly diminished in the PMI patients' group against the risk children' group, while the Ch/HDL-Ch rate was significantly elevated. PMID- 1742047 TI - The redistribution of the blood flow under nifedipine treatment in the sheep foetuses. AB - The Ca(++)-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus. This paper examines the effects of nifedipine on the foetus when administered to the pregnant ewe. Catheters and electrodes were implanted by surgical procedures in 15 ewes and foetal lambs between days 118 and 122 of gestation. The redistribution of foetal blood flow was measured by the radioactive microsphere injection technique. The infusion of nifedipine caused a 9% increase in the combined ventricular output (CVO) from 446 to 509 ml/min/kg in the foetus. Foetal lung blood flow increased from 29 +/- 6 to 69 +/- 14 ml/min/kg while figures for the skeletal muscle flow were 109 +/- 34 and 141 +/- 41.6 ml/min/kg. Heart and brain blood flow, expressed as percentages of CVO showed variations of 4.3 and 5.6 percent, respectively. Blood flow in the gut, placental membranes, skin, kidney and spleen was reduced. The present results show that nifedipine, in addition to its known effects causes a redistribution of the foetal circulation. PMID- 1742048 TI - Effects of prostaglandin E2 on the newborn respiratory system. AB - To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2 to 6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0 and 5.0 ug/kg/min: 30 min for each dose) into the ascending aorta. PGE2 caused significant, progressive decrease in ventilation (due to decreased tidal volume and breathing rate) heart rate, blood pressure and percent of the time spent in low voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia and increased frequency and duration of apneic events (greater than 3 sec). During the infusion, there was a dose related increase in plasma concentration of PGE2. At 30 min post-infusion, all measured variables showed recovery, although arterial pH carbon dioxide tension and plasma PGE2 remained significantly different from control values and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth. PMID- 1742049 TI - Erythrocyte damage in newborn babies caused by hyperbilirubinaemia and hypoxia. AB - Erythrocyte damage of newborn babies suffering from hyperbilirubinaemia and hypoxia was compared with a control group. In the cases of serum bilirubin level higher than physiological icterus lipid peroxidation of erythrocytes decreased probably due to the antioxidant effect of bilirubin. Moreover, an increase in potassium and protein outflow from patients' red blood cells was observed indicating a membrane damage both in hyperbilirubinaemic and hypoxic groups. Superoxide dismutase activity of serum and erythrocytes did not show significant difference in patients compared with healthy newborns. However, the low serum coeruloplasmin level in the hypoxic group and the low serum transferrin level of babies both with hypoxia and hyperbilirubinaemia suggest an insufficient antioxidant defence against free radicals. PMID- 1742050 TI - An aetiological study on 6 to 14 years-old children with severe visual handicap in Hungary. AB - A population-based aetiological study was carried out on 6 to 14 years-old severely visually handicapped children in Hungary. Of the 547 recorded cases 491 (90%) were included in the analysis. Eleven aetiological groups were separated: isolated cataracts (16.7%), congenital abnormalities of the eye (15.1%), high myopia +/- retinal detachment and other cases (13.4%), retinopathy of premature (11.0%), choroidoretinal degenerations (10.0%), syndromes (9.6%), nystagmus and/or hypermetropia (9.0%), isolated and complicated optic atrophy (6.7%), postnatal causes (4.9%), retinoblastoma (1.8%), prenatal causes (1.8%). A significantly higher rate of previous induced abortions was found in the group of retinopathy of premature. Perinatal damage syndrome and Mendelian monogenic defects are the two most common aetiological categories in the origin of severe visual handicaps in Hungary. PMID- 1742051 TI - In vitro effect of antitumor drugs on lymphocytic blastogenesis in childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). AB - "In vitro" sensitivity of lectin (PHA, Con A)-stimulated lymphocytes to antitumor drugs (ARA-C, ADR, VM26, MTX, CP, VCR, Vepesid, ACLA) and the clinical efficiency of the complex therapy was compared in 7 patients with ALL and 2 patients with NHL. H3-thymidin incorporation of lymphocytes labelled prior to the drug exposure was used as "in vitro" method. A fairly good correlation was found between the "in vitro" test and the clinical response to the drug administered. These results suggest that this "in vitro" test is useful in choosing the drugs to be administered in case of malignancies of children. PMID- 1742052 TI - Preparation, sedation, and monitoring of the pediatric patient in the magnetic resonance suite. PMID- 1742053 TI - Magnetic resonance imaging of the infant brain. PMID- 1742054 TI - Magnetic resonance imaging of the pediatric spine. PMID- 1742055 TI - Magnetic resonance imaging of the pediatric thorax. PMID- 1742056 TI - Magnetic resonance imaging of the pediatric abdomen. AB - In many ways, MRI of the pediatric abdomen is in its infancy. Motion will be a problem with most of the current pulse sequences, but the problem appears manageable given many of the newer software options for motion suppression. Faster pulse sequences (approaching CT scan times) will serve to improve image quality and reduce the need for sedation. Identification of a reliable enteric contrast agent probably will expand the current utility of MRI beyond evaluation of solid abdominal viscera. Although preliminary results appear promising, controlled comparative studies are necessary to determine the exact role of MRI in diagnosis and staging of common pediatric abdominal malignancies. The addition of MRI intravenous contrast agents and MR spectroscopy are anticipated to add depth and specificity to the diagnostic potential of this exciting modality. PMID- 1742057 TI - Magnetic resonance imaging of the pediatric pelvis. PMID- 1742058 TI - Magnetic resonance imaging of the pediatric musculoskeletal system. PMID- 1742059 TI - [Endoscopic naso-sinus surgery. Technical aspects]. AB - Perioperative, anaesthetic and special technical aspects of endoscopic surgery of the paranasal sinuses are presented, which helped to reduce intraoperative bleeding and consequently shortened the time of surgery. The realization of certain operative steps has helped to ease the postoperative care accelerating the healing process in more than 400 cases. PMID- 1742060 TI - [Multiple primary tumors in head and neck oncology]. AB - After establishing the conditions for considering tumours to be of the second primary type, these are classified into groups based on the chronological relation among the different lesions. According to placement, we differentiate some specific locations, which confer special characteristics to each case. The case histories of a series of patients, suffering from multiple primary tumours, are presented, covering each of the categories of the preceding classifications by typical clinical cases. Finally, a discussion is undertaken of the conceptual, diagnostic and therapeutic peculiarities which make these patients all too often difficult to interpret. PMID- 1742061 TI - [Topographic and cytoarchitectonics analysis of the vestibular complex in rats]. AB - The limits of the vestibular nuclei and accessory groups were analyzed in 7 rats. This information was taken using camera lucida drawings of the vestibular nuclei and their neurons in serial sections. The study of the morphometric parameters of the neurons (area and maximum diameter) were accomplished by means of a program for image analysis. The cells of the superior nucleus had an area and maximum diameter of 302.05 microns2 and 24.05 microns, those of the medial nucleus 222.98 microns2 and 20.49 microns, those of the lateral nucleus 609.94 microns2 and 34.21 microns, and the descending nucleus cells 327.55 microns2 and 25.24 microns. The cellular parameters of the associated groups were also studied and the distribution of them in several intervals was established. PMID- 1742062 TI - [Horizontal supraglottic laryngectomy. A study of 83 cases]. AB - We present the results obtained in 83 patients with supraglottic laryngeal carcinoma treated by supraglottic laryngectomy. We studied the results, complications and the survival of these patients treated with this conservative surgery. We concluded that this surgical technique improved the survival rates in supraglottic carcinomas. PMID- 1742063 TI - [Use of morphophotometry in the study of the kinetics of cell populations in laryngeal epidermoid carcinoma]. AB - The use of morpho-photometric techniques in anatomopathology is, on the whole, not very frequent at the moment. In this study the authors show the possible applications of these quantitative methods for the evaluation of kinetics characteristics of cell population in epidermoid carcinomas of the larynx. PMID- 1742064 TI - [Physical separation of the populations of cochlear and vestibular efferent somas. A study using horseradish peroxidase]. AB - We have physically separated cochlear and vestibular end organs, and after injecting horseradish peroxidase two different populations of efferent somas have been described belonging to the cochlea and vestibule. PMID- 1742065 TI - [Mastoid osteoma]. AB - Extra-canalicular osteomas of the temporal bones are rare benign tumours. We report a retroauricular osteoma in a 18 years old patient. Usually symptomless, they may present for cosmetic reasons. We briefly comment this type of tumours. PMID- 1742066 TI - [Craniopharyngioma of the nasopharynx. Apropos of a case]. AB - A case report of a nine year-old child with a basal skull and nasopharynx craniopharyngioma, whose initial manifestation was nasal respiratory insufficiency and ophthalmologic pathology, is presented. The diagnosis was possible due to some Departments collaboration by excellent images of CT and MR and confirmed histopathologically after its total excision performed by U. Fisch type C infratemporal approach, which is used for nasopharyngeal carcinomas and juvenile angiofibromas. PMID- 1742067 TI - [Extramedullary plasmocytoma of the nasopharynx]. AB - A case of extramedullary plasmacytoma sited in the nasopharynx in a 25 years old women is presented. The first symptomatology was otology; no evidence of plasmocytoma after clinical study were found in another site. We also do a revision of diagnostic and therapeutic management. We ind this case interesting because his site of origin and the patient's sex. PMID- 1742068 TI - [Solitary extramedullary plasmocytoma of the nasal cavity]. AB - A case of Extramedullary Plasmacytoma of nasopharynx is reported in a 41 years old man. The presenting symptom was bilateral nasal obstruction. Multiple Myeloma was excluded. The treatment was surgical excision and postsurgical radiotherapy. At present the patient is well. PMID- 1742069 TI - [Warthin's tumor: clinical aspects and a cytological study using fine-needle puncture-aspiration in 16 cases]. AB - The clinical and fine-needle cytologic findings of 16 Warthin's tumors (papillary cystadenoma lymphomatosum) are presented. They were studied during a period of 38 months, between February 1987 and April 1990. A preoperative diagnosis of "Warthin's tumor" was made in 13 cases (80%); 3 cases were diagnosed as non neoplastic benign lesions (2 retention cysts and 1 chronic sialoadenitis). 10 cases were surgically excised and preoperative diagnosis was histologically confirmed. We compare the cytologic findings of our cases with the literature ones. PMID- 1742070 TI - [Pharyngo-laryngeal spindle cell carcinoma]. AB - Spindle cell carcinoma, a relatively uncommon neoplasia in the otorhinolaryngologic field has a benign polypoid appearance, and often results in diagnostic and therapeutic difficulties. A review of the published literature, and of all of the eight cases we have had in our department has been made, with special attention-being pad to anatomopathologic diagnosis, treatment and prognosis. To sum up, it represents a malignant neoplasia epithelial in origin and of a difficult clinical and pathological diagnosis, which would be more adequately treated by surgical exeresis. It has a worse prognosis than epidermoid carcinoma which is common in this part of the throat. PMID- 1742071 TI - [Undifferentiated carcinoma of the ear: apropos of a case]. AB - A case report of ear undifferentiated squamous cell carcinoma is presented. The patient complained pain and suppurative ear, which lead to us to practise an exploratory atticotomy, and therefore the tumor was detected on its early stages. It is a very interesting case report due to its unusual localization, and to the early diagnosis to improve the prognosis of these patients. PMID- 1742072 TI - [Hemangiopericytoma of the maxillary sinus: apropos of a case]. AB - Haemangiopericytoma is a rare vascular tumour arising from the proliferation of pericytes which are cells surrounding the capillaries. Since 1949 only 54 cases of haemangiopericytomas of the nose and paranasal sinuses have been reported in the literature. Of the latter, only 8 cases originated from the maxillary sinus. We report a further case originated from the maxillary sinus. PMID- 1742073 TI - Value of HIV transmembrane glycoprotein oligomers as target antigens in early detection of anti-env antibodies. PMID- 1742074 TI - Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. AB - A recombinant vaccinia virus in which the transcription of the human immunodeficiency virus type 1 (BRU isolate) env gene is driven by the 11K late vaccinia promoter yields about 10-fold higher amounts of gp160 env protein upon infection of monkey cells than does a recombinant in which gp160 is expressed using the 7.5K early-late promoter. The gp160 was purified from detergent lysates of infected cells by lentil lectin affinity chromatography followed by immunoaffinity chromatography, and was obtained in yields of 1-2 mg/10(9) cells of material estimated to be about 70% pure. Pairs of rabbits were immunized with purified gp160 using either one of five different adjuvants or an immunostimulating complex. In all cases a substantial humoral immune response was obtained after boosting, including an activity that neutralized the homologous (BRU) isolate of HIV-1. In some cases, this activity also neutralized two distantly related isolates, SF2 and MN. PMID- 1742075 TI - Initial stages of HIV-1 envelope glycoprotein-mediated cell fusion monitored by a new assay based on redistribution of fluorescent dyes. AB - Membrane fusion is an essential step in the infection of permissive cells with human immunodeficiency virus (HIV). Infected cells frequently fuse with each other, and then progress to form multinucleated giant cells (syncytia). To gain insight into mechanisms of HIV env-mediated membrane fusion, we developed a new assay for studying the initial events. The assay is based on the redistribution of fluorescent markers between membranes and cytoplasm of adjacent cells examined by means of fluorescence video microscopy. Membrane fusion between HIV-1 envelope glycoprotein (gp120/41) expressing effector cells and CD4+ target cells was observed 90 min after the association of cells, whereas the first syncytia only became apparent after 5 h. Moreover, membrane fusion events were observed under conditions where no syncytia were detected, for example, when the effector:target cell ratio was greater than 100:1, or less than 1:100. A significant number of cells with fused membranes were not involved in the syncytia. In order to determine whether quantitative differences in receptor expression might influence the extent of membrane fusion, we used laboratory-selected variants of CEM cells that differ in their expression of CD4. We found that CD4 is required on the target membrane for HIV env-mediated membrane fusion, but its extent is only partially dependent on CD4 surface concentration. The ability of those CEM variants to take part in HIV env-mediated membrane fusion did not correlate with their capacity to form syncytia. These findings indicate that additional steps are needed to form syncytia after membrane fusion. PMID- 1742076 TI - Cellular and antibody responses directed against the HIV-1 principal neutralizing domain in HIV-1-infected children. AB - The principal neutralizing domain (PND) for antibody response is located within the V3 variable region of gp120 and can also stimulate T-cell responses. In some adults infected with human immunodeficiency virus (HIV) an HIV-1-specific T-cell response can be detected by demonstrating in vitro proliferation to HIV-1 proteins and peptides. In other HIV-1 infected adults an HIV-1-specific T-cell response can involve interleukin 2 (IL-2) secretion in the absence of T-cell proliferation. To elucidate the T-cell responses to PND in children, we examined the proliferative and the IL-2 secretory responses of peripheral blood lymphocytes from 19 HIV-1-infected children toward a peptide which contained a highly conserved sequence of the principal neutralizing domain of HIVMN (PND-MN). Stimulation with PND-MN induced proliferation of lymphocytes from 2 of the children and IL-2 secretion by lymphocytes from 5 of the children. In a 3-month old infant, the in vitro cellular response to the PND-MN indicated HIV-1 infection prior to the detection p24 antigen in her serum. Although antibodies directed against PND-MN were detected in all but one of the children examined, the presence of high-affinity/avidity antibodies to the PND-MN correlated with the presence of a cellular response to PND-MN. Thus, in HIV-1-infected children an HIV-1 specific T-cell response in the absence of a proliferative response can be assessed by determination of the IL-2 secretory response and correlates with the generation of high-affinity/avidity antibodies. PMID- 1742077 TI - Characterization of IgG and IgG subclass antibodies present in paired maternal and fetal serum which are directed against HIV-1 proteins. AB - Passive immunity is conferred to the fetus by maternal antibodies, the majority of which are transported across the placenta during the third trimester of pregnancy. To determine the placental transport of anti-HIV-1 antibodies, serum from 5 women infected with human immunodeficiency virus (HIV) and their abortuses were examined for anti-HIV-1 antibodies. The gestational age of the abortuses ranged from 18 to 24 weeks and following polymerase chain reaction amplification, HIV-1 gag DNA was detected in tissue from 2 of the abortuses. The concentration of total IgG antibodies present in cord blood ranged from 2.9% to 12.5% of maternal levels. Antibodies directed against the envelope proteins, gp160 and gp120, the reverse transcriptase protein, p66, and the capsular protein, p24, were present in fetal and maternal serum. Although IgG1 was the predominant subclass antibody generated in response to HIV-1 proteins, IgG2, IgG3, and IgG4 directed against HIV-1 proteins were also detected. There were large differences in the antigens recognized by the antibodies produced in the mothers, and the IgG subclasses of the antibodies produced. HIV-1 proteins recognized by antibodies present in cord blood were similar to those recognized by paired maternal serum and IgG1, IgG2, IgG3 recognizing HIV-1 proteins were detected in fetal serum. However, there was a dichotomy in placental transport of IgG subclass antibodies to HIV-1 proteins. The role of these antibodies in prevention of vertical transmission of HIV-1 has yet to be determined. PMID- 1742078 TI - Human astrocytes stimulate HIV-1 expression in a chronically infected promonocyte clone via interleukin-6. AB - Human promonocyte cells chronically infected with human immunodeficiency virus type (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by human astrocytes and glioma cell lines U251 and 253. HIV-1 expression was assessed by measuring reverse transcriptase activity. All media conditioned by unstimulated and lipopolysaccharide (LPS) stimulated glial cells induced HIV-1 expression and contained detectable levels of interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha). An antibody against IL-6, but not against TNF alpha, reduced the induction of HIV-1 by the conditioned media in a concentration dependent manner. The magnitude of HIV-1 induction by the conditioned media was proportional to the concentration of IL-6 in them. The data indicate that normal and transformed human astrocytes are capable of stimulating HIV-1 expression in chronically infected promonocytic cells by secreting IL-6. The results demonstrate that cytokines secreted by neural cells could play an important role in regulating HIV-1 expression in the brain. PMID- 1742079 TI - Ultraviolet radiation increases HIV-long terminal repeat-directed expression in transgenic mice. AB - Previously described FVB/N mice harboring a human immunodeficiency virus (HIV) long terminal repeat (LTR)/chloramphenicol acetyl transferase (CAT) transgene were treated with varying amounts of 254 nm UV-C radiation or 312 nm UV-B radiation. At optimal exposure periods, a 20-fold increase in HIV-LTR-directed expression was observed in ear specimens collected 24 h following UV-C exposure; a fourfold increase in expression was induced by UV-B exposure. Investigation of the kinetics of UV-C induction in vivo revealed that LTR-directed gene expression began to increase 2 hours after exposure and reached a maximum on Day 3 following exposure (greater than 30-fold induction). In experiments examining the kinetics of UV-B activation, the maximum level of CAT activity in the ears of irradiated transgenic animals was fivefold above levels in unirradiated transgenic controls (Day 5). Furthermore, CAT activity was not induced in fur-bearing skin following UV exposure; however, a fourfold increase in HIV-LTR-directed expression could be elicited when hair was removed by shaving prior to UV-B treatment. PMID- 1742080 TI - Cell-mediated infection of human placental trophoblast with HIV in vitro. AB - In order to investigate how human immunodeficiency virus (HIV) gains entry to the placenta, we have performed in vitro experiments in which highly purified trophoblast cells isolated from term human placentas were examined for their susceptibility to HIV infection. Trophoblast cells were exposed to cell-free HIV 1 for up to 24 h, after which the cultures were monitored by p24 antigen capture assay, reverse transcriptase assay, and electron microscopy for evidence of virus uptake and replication. None was found. In the second series of experiments, trophoblast cells were cocultured with HIV-infected MOLT-4 cells for 24 h, stained using an anti-HIV antibody, and examined by immunofluorescence microscopy. The MOLT cells were strongly positive, as expected, but many trophoblast colonies also showed a punctate staining pattern. Examination of similar cultures using the electron microscope revealed MOLT cells adherent to trophoblast but no evidence of cell-cell fusion. Virions were observed in coated pits at the trophoblast cell surface and in endosomes or multivesicular bodies in the cytoplasm. These observations are consistent with an endocytosis-mediated mechanism of virus entry. Virions were also observed budding from the trophoblast plasma membrane, indicating that these cells can support HIV replication. To our knowledge, these results show for the first time that HIV can infect placental trophoblast cells in vitro. The results suggest that the placenta could become infected with HIV by the interaction of virus-infected maternal lymphocytes with syncytiotrophoblast bordering the maternal blood in the intervillous space. PMID- 1742081 TI - Soluble CD4-PE40 is cytotoxic for a transfected mammalian cell line stably expressing the envelope protein of human immunodeficiency virus (HIV-1), and cytotoxicity is variably inhibited by the sera of HIV-1-infected patients. AB - Sera were obtained from 50 individuals infected with human immunodeficiency virus type 1 or from HIV-1-uninfected individuals before or after vaccination with recombinant gp160. These sera were evaluated for activity antagonistic to the cell-killing activity of the chimeric Pseudomonas exotoxin hybrid protein, sCD4 PE40. For these studies, Chinese hamster ovary (CHO) cells were transfected with a chimeric plasmid encoding the tat, rev, and envelope genes of HIV-1 and a cell line was selected for stable expression of the envelope glycoproteins at the cell surface (CHO-env). Cytotoxicity of sCD4-PE40 for CHO-env in the presence or absence of added human serum was quantitated spectrophometrically following enzymatic reduction of a tetrazolium bromide within the mitochondria of viable cells (MTT assay). Several HIV+ sera inhibited the cytotoxic activity of sCD4 PE40; the antagonist had properties consistent with those of immunoglobulins in that it was heat stable, absorbed by protein A, and reversible by increasing the concentration of sCD4-PE40. Of 15 HIV+ sera which strongly reacted with gp120, 11 (73%) also potently inhibited sCD4-PE40 cytotoxicity, and cytotoxicity was inhibited by sera from some HIV- individuals after, but not before, immunization with gp160. These data suggested a role for antibody to gp120 in the antagonistic activity. However, not all sera with antibody to gp120 antagonized sCD4-PE40 cytotoxicity and high levels of antagonist activity were frequently (40%) found in HIV+ sera lacking immunoblot-detectable antibody to gp120, or antibody to either CD4 or PE40. Grouping of the HIV+ sera according to the patients' absolute number of CD4+ cells revealed that the degree of inhibition of sCD4-PE40 cytotoxicity approached a Gaussian distribution, suggesting that persons with CD4+ cell counts between 200 and 700/mm3 may be more likely to possess significant levels of serum antagonist. This data have implications for the clinical development of sCD4-PE40 or other sCD4-based therapeutics in the management of HIV-1 infection. PMID- 1742082 TI - Intracellular metabolism of 3'-azidothymidine in isolated human peripheral blood mononuclear cells. AB - Azidothymidine (AZT) inhibits the replication of human immunodeficiency virus and it is the only drug so far licensed for treatment of acquired immunodeficiency syndrome (AIDS). A prerequisite for its antiviral activity is phosphorylation by cellular nucleoside kinases to the mono-, di-, and triphosphate levels. This study determined the capacity of isolated peripheral blood mononuclear cells (PBMC), resting or mitogen stimulated, from 36 different people of whom 5 were HIV+, to phosphorylate and accumulate intracellular AZT nucleotides. We found a large variation in the amount of products formed between PBMC treated at different times from the same individual as well as between the PBMC from different individuals. Resting PBMC showed the largest interindividual variation and their levels of AZT nucleotides were about 60-150-fold lower than in activated PBMC. The intracellular half lives of azidothymidine mono-, di-, and triphosphates, constituting, on the average, 96-99.2, 0.7-1.8, and 0.4-2.7% of total nucleotides at 0.08-1.6 microM AZT, respectively, were also determined. In mitogen-stimulated PBMC it was approximately 2.5 +/- 0.6 h for all the azidothymidine metabolites. The half-life for intracellular azidothymidine monophosphate in resting PBMC from two individuals was determined to 1.5 +/- 0.2 h. There appeared to be no significant difference in the AZT metabolism in PBMC from HIV-positive or-negative persons. A relative decrease in the intracellular formation of AZTDP and AZTTP from AZTMP was observed at concentrations of AZTMP above 1 microM. This fact may explain why lowering the doses of AZT still gives therapeutically efficient levels of the active metabolite AZTTP. PMID- 1742083 TI - Changes in lipid composition of human peripheral blood lymphocytes infected by HIV. AB - The possible differences in lipid composition between human immunodeficiency virus- (HIV) infected and uninfected PHA-activated human peripheral blood mononuclear cells (PBMC) have been studied. The total fatty acid composition was similar, except for the proportion of arachidonic acid, that was slightly higher in infected than in noninfected cells. No significant differences were obtained in the incorporation of radiolabeled stearic or oleic acids in the different lipid classes. The staining of cells with Nile Red showed similar amounts of intracytoplasmic lipid droplets. On the contrary, the CH/PL ratio, the major factor in determining cell membrane fluidity, was clearly higher in infected than in uninfected cells (0.60 and 0.36, respectively). This fact is discussed in relation with the known high CH/PL ratio (0.95) of the lipid envelope of HIV. PMID- 1742084 TI - Selective stimulation of CD4+ versus CD8+ T-cell subsets in symptomatic and asymptomatic HIV-1-infected individuals. AB - To analyze the proliferative capacity of CD4+ or CD8+ T-cell subsets of individuals infected with human immunodeficiency virus type 1 (HIV-1) and to optimize the in vitro conditions for virus replication, CD4+ or CD8+ cells of HIV 1-infected patients were selectively activated inside the whole peripheral blood mononuclear cell (PMNC) population by dual antibody stimulation. To do so PMNC of HIV-1-infected individuals were stimulated with the per se nonmitogenic anti-CD3 antibody fragment BMA030 F(ab)2 crosslinked through goat antimouse antibodies with an anti-CD4 or an anti-CD8 antibody, which lead to selective proliferation of either the CD4+ or the CD8+ T-cell subset. In the presence of monocyte supernatant and recombinant interleukin-2 (rIL2) CD4+ cells of HIV-1 patients responded normally upon such stimulation as their proliferation correlated (r = 0.9) to the percentage CD4+ cells present in the PMNC population. Selective stimulation and proliferation of CD8+ cells could, however, only partially be elicited by dual antibody stimulation, even in the presence of rIL-2 and monocyte supernatant. Their proliferative response did not correspond (r = 0.1) to the percentage CD8+ cells present in the PMNC culture. A positive correlation (r = 0.7) was detected only between percentage CD8+ HLA-DR- cells and proliferation. This confirmed previous studies showing that the defective in vitro proliferative response of peripheral blood lymphocytes of HIV-infected individuals to mitogens, which is usually interpreted being due to a CD4 cell defect, is actually due to a failure of CD8+DR+ cells to proliferate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742085 TI - Lymphoproliferative responses to mitogen and antigen in HIV-infected children. AB - We endeavored to study lymphoproliferative responses in children with human immunodeficiency virus (HIV) infection and to compare them with normal control children. Children were grouped according to age; 6-18 months and greater than 18 months, and according to CDC classification: asymptomatic (P1), mildly symptomatic (P2A), and advanced symptoms (P2D). Absolute CD4 and CD8 numbers were compared and found to be higher in the younger age groups. The children in P1 and P2A classes demonstrated an increase in CD8+ cells; only the children with AIDS showed a significant decrease in CD4+ cells. Lymphoproliferative responses to phytohemagglutinin A (PHA) were compared to tetanus toxoid. Only the children with acquired immunodeficiency syndrome (AIDS) (P2D) in the older group and only the symptomatic children (P2A and P2D) in the younger group showed a significant decrease in proliferative responses to PHA. All classes of infected children demonstrated a significant decrease in response to tetanus toxoid. We have been able to demonstrate a loss of antigen responsiveness which precedes the loss of mitogenic responsiveness. Furthermore, we have been able to demonstrate an age related increase in lymphoproliferative responses to both PHA and tetanus in HIV infected and control children. Therefore, we conclude that children are particularly susceptible to the immunologic effects of HIV infection. Loss of lymphoproliferative responses to antigen occurs early in infected children and precedes the loss of CD4+ helper cells and of PHA responsiveness. This increased susceptibility to the immunopathogenesis of HIV infection is due, at least in part, to the relative immunodeficiency of infancy. PMID- 1742086 TI - Enzyme immunoassay for detection of hybrids between PCR-amplified HIV-1 DNA and a RNA probe: PCR-EIA. PMID- 1742087 TI - [Cerebral infarction and chronic cerebral circulatory insufficiency]. PMID- 1742088 TI - [MRI in patients with cerebral infarct and chronic cerebral circulation insufficiency]. PMID- 1742089 TI - [Issues concerning diagnosis of lacunar stroke and RIND]. PMID- 1742090 TI - [Cerebral blood flow in cerebral arteriosclerosis and cerebral infarction]. PMID- 1742091 TI - [Intrathecal distribution of ACNU by various modes of its administration analyzed by HPLC and autoradiography]. AB - Various modes of administration of ACNU (nimustine hydrochloride) were tried to make clear which mode is the best method to obtain intrathecal diffuse distribution of ACNU to match the condition of killing of glioma cells (10 micrograms/ml; greater than 30 min.). Tried modes of administration included 1)bolus injection into ventricular cavity, 2)bolus injection into cisterna magna, 3)bolus injection into lumbar subarachnoid space, 4)ventriculo-lumbar perfusion, 5)chiasmatic cistern-lumbar perfusion. Used dose of ACNU was 5 mg/body for all modes of administration. ACNU level in CSF was measured by HPLC method specially developed by authors. To make clear intrathecal distribution of ACNU, autoradiography using 14C-ethylene-ACNU was studied after administration of 10 muCi/Kg of radioactive ACNU. The images were studied by image analyzer system (BAS-2,000 system developed by Fuji Film Co. Ltd). Among the modes of administration tried, ventriculo-lumbar perfusion method gave the best results in terms of lumbar, ventricular, cisterna magna, and basal cistern distribution of ACNU to match the cell kill condition experimentally ascertained. Although, bolus injection of ACNU into cisterna magna gave sufficient amount of ACNU in lumbar region, the initial level of ACNU was too high in cisterna magna, and administration of ACNU once a week for three times in a canine cisterna magna resulted in considerable deterioration of brain stem and basal structure. In addition to it, the level of ACNU in ventricular cavity was not detectable. Lumbar bolus injection resulted in also too much ACNU accumulation at the injected lumbar area, and at the cisterna magna region, ACNU was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742092 TI - [Alterations in cytokinetics and heat shock protein (70 kDa) expression of glial cell by hyperthermia]. AB - Expression of major heat shock and stress-induced protein, HSP70, is known to be under complex regulation in tumor cells. In this study, we investigated the alternations of cytokinetics and HSP70 expression by hyperthermia in the in vitro experimental systems, using two rat glioma cell lines, two human glioblastoma cell lines and rat glioblast cells. For hyperthermal treatment the flasks were placed in water baths warmed up at 41 -45 degrees C for 15 min. To determine the effect of hyperthermia on the cell cycle progression, the changes in the DNA distribution of the cell population were studied by flow cytometry (FCM). The levels of HSP70 protein were determined by immunoblot analysis. The relationship between cell cycle and HSP70 expression was investigated by FCM using PI and FITC labelled HSP70 double staining technique. These results were as follows: 1) Compared with the control, hyperthermic treatment at 42 degrees C or 44 degrees C caused both 354A and T98G cells to accumulate in S phase 18 hours after treatment and G2/M phase after 6-18 hours. 2) Hyperthermic treatment at 42 degrees C caused C6 cells to accumulate in S phase 6 hours after treatment, whereas heat treatment at 44 degrees C caused C6 cells to accumulate in S phase after 18 hours and G2/M phase after 6 hours. 3) A172 cells were accumulated only in G2/M phase by hyperthermia. 4) Glioblast cells did not show the alterations of cytokinetics by heat treatment remarkably. 5) HSP70 protein synthesis were enhanced under hyperthermic conditions in all type of cells, whether primary glioblast or permanent glioma cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742093 TI - [Visual impairment complicated with meningioma]. AB - Among 106 patients of meningioma surgically experienced the past 10 years between 1981 and 1990, twelve of meningioma with progressive visual impairment were analyzed in relation to postoperative visual outcome. There were four males and eight females, and the age ranged from 33 to 61 years with the average 48 years. The distribution of tumor location was 6 cases in tuberculum sellae, 3 cases in the inner side of sphenoid ridge, and 3 cases in olfactory groove. The size of tumor in each case was 2 to 7 cm in diameter, and in 8 cases more than 3 cm. The duration of visual disturbance was between 3 months and 10 years with the average 3 years. For all cases, surgical removal of the tumor was performed totally by pterional and bifrontal approach. Consequently, 58.3% of 7 cases had improved vision postoperatively, 16.7% of 2 cases remained unchanged, and 25.0% of 3 cases were worse, including one case of malignant meningioma, Visual outcome was mainly affected by a duration of symptoms, a tumor size, a preoperative visual impairment, and in special, a situation of optic nerve where compression of tumor itself and adherence to the surrounding tissues took place. On operation, great care should be paid for a case of long-standing, severe visual disturbance as demonstrating hemianopsia with visual narrowing less than 50 degree by perimetry, and also for preservation of the feeding arteries of optic nerves. PMID- 1742094 TI - [An autopsy case of progressive supranuclear palsy with olivary hypertrophy]. AB - Clinical and pathologic findings of an autopsy case of progressive supranuclear palsy (PSP) with a 7 year clinical course are described. The patient exhibited clinical findings of typical PSP, cerebellar signs and rhythmical myoclonus that was about 2 Hz and synchronous in the eyes, palate, and pharynx, which is so called palatal myoclonus. Pathological findings compatible with those in PSP i.e. loss of nerve cells, neurofibrillary tangles (NFT), and gliosis were found in the globus pallidum, thalamus, subthalamic nucleus, substantia nigra, locus coeruleus, nucleus of Raphe, reticular formation, dentate nucleus, and inferior olives. Nerve cells in the nucleus basalis were preserved. Distinctive findings included marked degeneration of the dentate nucleus, prominent hypertrophy of the inferior olives, and atrophy and subcortical gliosis of the frontal lobe. Hypertrophy of the inferior olives and palatal myoclonus represent an unusual PSP. It is presumed hypoxic injury unmasked the palatal myoclonus in this setting of dentate nucleus and inferior olivary complex degeneration. PMID- 1742095 TI - [Generalized choreic movement associated with subarachnoid hemorrhage]. AB - A case of generalized choreic movement associated with subarachnoid hemorrhage is reported. A 71 year-old hypertensive woman suddenly developed severe headache 14 days before admission. Consciousness disturbance and involuntary movement involving the face and upper extremities appeared about 8 days after onset. The involuntary motion was diagnosed as generalized choreic movement. CT scans showed subarachnoid hemorrhage with ventricular dilatation and periventricular lucency involving bilateral caudate nuclei. On admission the patient was stuporous with Hunt & Kosnik Grade 4. She showed involuntary choreic movement in both arms, trunk and face; hemiparenis and hyperreflexia were absent. An angiography revealed a right internal carotid-anterior choroidal artery aneurysm with vasospasm. After clipping the aneurysm in the following day, the consciousness disturbance and choreic movement gradually improved. By eight days after operation, the choreic movement completely disappeared. An MRI showed lacunar infarcts in the bilateral basal ganglia, predominantly in the caudate nuclei. In our case, the choreic movement is supposed to have been caused by impaired circulation in the bilateral corpora striata due to vasospasm and hydrocephalus after subarachnoid hemorrhage, in addition to the preexisting lacunar infarcts in the basal ganglia. This is claimed to be the first reported case of generalized choreic movement in associated with subarachnoid hemorrhage, which improved after surgery. PMID- 1742096 TI - [An evaluation of cerebral blood flow and metabolism of reconstructive vascular surgery using positron emission tomography--a report of 4 cases]. AB - Changes in cerebral hemodynamics due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET). Three minor stroke cases and 1 TIA case, brought on by main trunk stenosis, were included. STA-MCA anastomoses was performed in two of the cases and carotid endarterectomy was performed in the remaining two cases. CBF, CBV, OEF, CMRO2 and CBF/CBV were investigated using PET with the ROIs fixed in both normal and stenosis areas. On the two cases of STA - MCA anastomosis, clear hemodynamic improvement was not demonstrated. On the two carotid endarterectomy cases, the hemodynamic factors showed improvement. PMID- 1742097 TI - [CT and 123I-IMP SPECT findings of head injuries with hyponatremia]. AB - CT and SPECT findings were examined and the relationship between development of hyponatremia and lesions was studied in cases who developed hyponatremia following head injury. Six cases of hyponatremia after head injury in the last two years were used as the subjects. SPECT was performed by the 123I-IMP intravenous injection method using Tomomatic 64. Slice 2 of 4 to 6 cm on the OM line in the early image was used as the subject site. The data of development of hyponatremia was 5.8 patients days, duration 9.2 days, minimum serum Na level 117.2 mEq/l and minimum plasma osmotic pressure 247.6 mOsm/lH2O. CT findings in the hyponatremic stage showed frontal subdural effusion in all the cases. SPECT findings revealed a decrease of CBF in the frontal region on both sides and in the central region. CBF in the central region also tended to improve at a time when hyponatremia improved. In hyponatremia after head injury, lesions are often found in the frontal region on CT, and CBF in the central region is also decreased bilaterally on SPECT, which is presumed to be concerned with the development of hyponatremia. PMID- 1742098 TI - Viorica Bergman. AB - Middle class, middle aged, female: I can hear the yawns already. This is not a description to conjure up the image of a forward-thinking, hard-working dentist with a wide portfolio outside her chosen profession. However, both descriptions apply to Viorica Bergman. PMID- 1742099 TI - Postgraduate qualifications for dentistry in the twenty-first century. AB - The publication by the General Dental Council of proposals for a specialist register brings into question the applicability of the postgraduate qualifications now available. The moves towards a collegiate home for general dental practitioners, and compulsory vocational training, are further reasons for contemplating radical change. PMID- 1742100 TI - 'Self-assessment manual of standards'. PMID- 1742101 TI - 'Maxillofacial surgery should become a specialty of medicine'. PMID- 1742102 TI - 'Orthodontic aspects of vocational training'. PMID- 1742103 TI - 'A denture of a lifetime'. PMID- 1742104 TI - Amalgam appendicitis. PMID- 1742105 TI - An urgent remedy needed. PMID- 1742106 TI - The clinical behaviour of free smooth surface carious lesions monitored over 2 years in a group of Scottish children. AB - As far as the authors are aware, no large-scale clinical studies of free smooth surface caries have been carried out in the past, although carious lesions on these surfaces can be diagnosed at an 'early' stage. In this study on a group of 2854 13-year-old children, caries affecting the free smooth surfaces (buccal and lingual) was found to be a common problem, with a total of 2917 lesions observed on molar teeth at the first examination. Most of the lesions involved no macroscopic loss of tooth contour. When the children were examined 2 years later, three-quarters of the lesions had either remained static or regressed. Free smooth surface lesions were more likely to develop initially, and more likely to progress, in individuals with poor oral hygiene. Free smooth surface caries experience showed a positive correlation with occlusal and approximal decay experience. The number of free smooth surface carious lesions can be used as a predictor of caries risk. Strategies for diagnosis and prevention are suggested for patients presenting with free smooth surface caries on molar teeth. PMID- 1742107 TI - The effect of residence and social class on dental caries experience in 15-16 year-old children living in three towns (natural fluoride, adjusted fluoride and low fluoride) in the north east of England. AB - Caries experience in 1374 children aged 15-16 years from three towns in the north east of England with varying concentrations of fluoride in drinking water, was determined. The mean DMFT values for 15-year-old continuous residents was 1.7 in Hartlepool (natural F 1.0-1.3 ppm), 2.5 in Newcastle (F adjusted to 1.0 ppm) and 3.3 in Middlesbrough (F = 0.2 ppm). Forty per cent of Hartlepool 15-year-olds were caries free, compared with 30% in Newcastle and 24% in Middlesbrough. Caries prevalence for both Hartlepool and Newcastle 'continuous residents' was lower than for non-continuous residents, whereas in Middlesbrough, the low fluoride area, non-continuous residents had a lower DMF value than those who had lived in Middlesbrough all their lives. There was a slight trend in both Newcastle and Middlesbrough for DMFT values to increase from social class I to social class V, but no discernable trend was observed in Hartlepool. The results for Hartlepool 15-year-olds were very similar to those reported by Weaver in 1949. PMID- 1742108 TI - Sarcoid-type reaction associated with retained roots: an unusual cyst-like lesion of the jaw. AB - This report describes the unusual findings following curettage of a large cyst like lesion of the mandible in a 47-year-old woman. Histological examination of the lesional tissue revealed a sarcoid-type reaction, uncommon in the mandible, while further clinical and laboratory investigations failed to demonstrate underlying systemic disease. PMID- 1742109 TI - The autobiography of Dr Lilian Lindsay. AB - Unwillingly, Lilian Lindsay started to commit to paper the story of her professional life, although, sadly, this did not progress further than the early years of her distinguished career. Her autobiography, entrusted to one of us with her personal historical notes and manuscripts in 1950, is published here for the first time, with annotations (in italics) to clarify the text by adding biographical details of persons she mentions and commenting on places and events. For some 40 years Lilian studied the history of dentistry, publishing many important papers as well as a book, Short History of Dentistry, but perhaps her most important contribution to dental history is her translation of Fauchard's Le Chirurgien Dentiste. PMID- 1742110 TI - Dental care for the homeless over Christmas 1990. AB - Each year since 1970, the charity CRISIS has provided a place of warmth and shelter for the homeless of London (guests) over the Christmas period. In 1990 they converted a large factory warehouse off the Old Kent Road and set it up to cook meals, provide beds, games, televisions, hairdressing, chiropody, medical and dental care--and information on housing, as well as general advice. Washing and cleaning facilities were provided in Portakabins parked in the yard outside the warehouse. Guests were provided with a complete change of clothing, which were altered to fit if necessary. PMID- 1742111 TI - What should dentists prescribe? AB - In recent months in Australia the, country's Association has been negotiating with the Federal Government over the rights of dentists to prescribe. The question is not the legal right to order a drug for a patient, but the entitlement of patients to a Government health scheme benefit for the dentist's prescription. The debate has, however, opened up broader questions. What is a reasonable extent of entitlement? What should a dentist be allowed to prescribe? PMID- 1742112 TI - After the contract ... which way now? AB - There can be little doubt that the treadmill of NHS dentistry has done little to improve standards, and one can only applaud those who are so actively seeking to do so. But, perhaps sometimes we should examine our motives. Why do we want to improve? We cannot all hope to provide the very best for everyone. There simply are not the funds or the dentists. Is it so that we can obtain more money, or greater job satisfaction, or to give the patient a better deal? PMID- 1742113 TI - Equipment malfunction. PMID- 1742114 TI - 'Decontamination of equipment, linen or other surfaces contaminated with hepatitis B and/or human immunodeficiency viruses'. PMID- 1742115 TI - 'HIV transmission via blood and saliva splashes to the face'. PMID- 1742116 TI - Computers in dentistry. PMID- 1742117 TI - Five-year longitudinal study of restorative treatment received by Scottish children. AB - This prospective 5-year longitudinal study followed the dental care of a large, representative group of children initially examined in Scotland during the 1983 UK survey of children's dental health. The Dental Health Services Research Unit at the University of Dundee monitored the restorative treatment provided in the General Dental Service and the Community Dental Service for 1568 children aged 5, 8, 12 and 15 years in 1983, using information provided via the Scottish National Health Service. Over a 5-year period, records of attendance were received for 85% of the children (1340). A large amount of restorative care, distributed very unevenly across the sample, was provided. On average, attenders attended once per year (range over 5 years: 1-20) and received approximately one filling in each of the 5 years (range over 5 years: 0-58). The majority of restorative care (80.6% of the 8057 restorations) comprised amalgam fillings in posterior teeth, frequently (89%) involving the occlusal surface. This pattern of treatment has implications for planning cost-effective preventive care. Factors shown to have a significant influence on the number of amalgam fillings placed were initial caries prevalence, number of courses of treatment, age group and service. PMID- 1742118 TI - An analysis of the effects of place of childhood, undergraduate and postgraduate education upon the regional distribution of specialist orthodontic practitioners. AB - In 1989, a survey of specialist orthodontic practitioners was carried out. Questionnaires were sent to all members of the British Association of Orthodontists who were engaged in full-time specialist practice. This yielded a response rate of 72%. One part of the questionnaire was directed towards details concerned with the practitioner's place of childhood, undergraduate and postgraduate education. The regions in the UK were grouped into two large areas of the 'north' and the 'south'. It was evident that most of the practitioners had received their orthodontic training in the 'south' of England and were employed within the same region. Detailed data analysis was carried out using the Mantel Haenszel chi-squared test. This revealed that there was a strong association between the place of postgraduate orthodontic training and place of employment of the specialist practitioner (chi 2 = 48.6, P less than 0.00001). The data suggest that one method of reducing the present unequal distribution of the specialist orthodontic practitioner would be to increase the number of postgraduate training places in those regions with low levels of orthodontic manpower. PMID- 1742119 TI - Surgical emphysema of the mediastinum as a consequence of attempted extraction of a third molar tooth using an air turbine drill. AB - The use of air turbines for the removal of bone or the division of teeth is to be deprecated. Surgical emphysema of the neck and mediastinum as a direct result of the inappropriate use of an air turbine drill to remove an impacted third molar tooth may result in potentially life threatening complications. PMID- 1742120 TI - A primary double molar tooth in a child with Russell-Silver syndrome. AB - The prevalence of double teeth in the primary dentition, for the British schoolchild, is 1.6%. Although primary double teeth in the anterior region of the mouth are not uncommon, double teeth in the primary molar region are rare. This case report describes the intra-oral findings, and in particular a case of a primary molar double tooth, in a young child who has Russel-Silver syndrome. PMID- 1742121 TI - Applications of confocal scanning optical microscopy to dentistry. AB - Confocal optical microscopy is now a well recognised technique in the fields of biological and materials science. This type of light microscope can be considered as being midway between optical and electron microscopy. Confocal or scanning optical microscopes can make high resolution, thin, optical sections within semitransparent samples such as biological tissues. Surface images of samples can be produced which are similar in character to those of the SEM, but without many of the problems of specimen preparation. The improved resolution and removal of out-of-focus blur allows much more information to be gained from fluorescence microscopy techniques, with the images capable of 3-D reconstruction of the sample. There are basically two types of confocal optical microscope: the laser scanning type (CLSM) and the real-time direct view of tandem scanning microscopes (TSM). The former are best suited to immunofluorescence microscopy, whilst the latter are more appropriate for high-speed reflection imaging, having originally been developed for in vivo microscopy. PMID- 1742122 TI - First steps in audit. AB - The results of two audit projects carried out in a District Orthodontic Unit are described. Although prospective data collection was the goal, it was found that this method yielded little information as the data collection forms were poorly filled in. The main problem was a lack of definition of terms and inadequate discussion between clinical and clerical staff. A retrospective audit using five clearly defined fields was more successful. It is very important that there is provision to verify the data collected. The time commitment for clinical staff should not be underestimated. PMID- 1742123 TI - High resolution CT and bronchography in the assessment of bronchiectasis. AB - To elucidate the reliability of CT in the assessment of bronchiectasis, a retrospective study of high resolution CT and bronchography was carried out. A segment by segment comparison of 259 segmental bronchi from 70 lobes of 27 lungs in 19 patients was performed using bronchography as standard. CT was positive in 87 of 89 segmental bronchi with bronchiectasis giving a false-negative rate of 2%. CT was negative in 169 of 170 segmental bronchi without bronchiectasis at bronchography, giving a false-positive rate of 1%. There was agreement between the two modalities in identifying the different types of bronchiectasis. PMID- 1742124 TI - Efficacy of inverted digital luminescence radiography in evaluating chest neoplasms. AB - Inverted (positive) digital chest radiographs of patients with lung tumors were compared with commonly used (negative) digital images, consisting of one simulated normal and one contrast enhanced image. The first part of the material consisted of 80 patients of whom 40 had tumors and 40 were normal. Five radiologists with different experience reviewed the examinations. From their answers, ROC curves were constructed. The second part of the material consisted of 100 chest phantom examinations with a simulated tumor in the mediastinum (45 examinations) and/or the left lung (46 examinations). In 31 exposures there was no abnormality. These were reviewed by 3 observers and performed as an ROC study as well. There was no statistical difference between the different types of images or between the observers in the 2 studies. PMID- 1742125 TI - CT for predicting the resectability of lung cancer. A prospective study. AB - In order to assess the accuracy of CT in predicting the resectability of lung cancer, a prospective study was performed on 96 patients undergoing thoracotomy. The tumors were classified preoperatively according to the TNM classification and the new international staging system for lung cancer, and scored as being resectable by lobectomy or pulmectomy, potentially resectable by lobectomy or pulmectomy, or nonresectable. Of the tumors predicted to be resectable or potentially resectable, 86.6% and 63% were radically resected, respectively, and the need for lobectomy versus pulmectomy was correctly estimated in 81.3% of them. The insufficiency of CT for defining lymph node metastases and infiltrative tumor growth was considered a marked disadvantage of the method. PMID- 1742126 TI - CT findings of endobronchial metastasis. AB - One hundred and sixty-one patients with pulmonary metastases were studied with CT. Six of them proved to have endobronchial (intraluminal) metastatic lesions by bronchoscopy. Retrospective analysis of the CT studies showed obstruction and/or narrowing of the bronchi in 5 cases while no lesion was observed in one patient. Although CT can not always demonstrate intraluminal lesions, it should be performed when an endobronchial metastasis from extrathoracic malignancy is seen by bronchoscopy because it will show hilar or mediastinal lymphadenopathy, or single or multiple pulmonary metastases other than the endobronchial lesion. PMID- 1742127 TI - Radiographic grading of extrinsic allergic alveolitis. A comparison between a modified ILO classification and a descriptive method. AB - We analyzed the acute phase radiographs of 107 consecutive patients with clinically confirmed extrinsic allergic alveolitis. Three readers independently recorded the profusion and the type of opacities according to the standard ILO criteria extended with categories x, y, z, and ground glass for description as proposed by McLoud et al. The profusion of the changes was grade 0 in 13%, grade 1 in 37%, grade 2 in 35%, and grade 3 in 15% of the interpretations. The type of predominant small opacities was p in 33%, x in 22%, s in 13%, t in 10%, q in 9%, and 0, r, u, y, and z in 13% of the interpretations. Ground glass density was seen in 8% of the recordings. The changes were predominantly located in the middle and lower lung zones. For comparison, according to the classification of Hapke et al. miliary changes (68%) predominated over fibrotic (27%) and normal (11%) recordings. The intraobserver agreement was good by both methods, but there was less interobserver variation with the ILO method. The semiquantitative standardized modified ILO scheme was considered more informative than Hapke's descriptive classification for epidemiologic and research purposes. PMID- 1742128 TI - Powdered diatrizoic acid for radiography of the respiratory tract. Part II. Clinical application. AB - The diagnostic and clinical value of 41 examinations using insufflation and/or inhalation of powdered diatrizoic acid for tracheobronchography, tracheography, laryngography, nasopharyngography, and sinusography was investigated in 35 patients. Diatrizoic acid was found to be useful when applied by insufflation for demonstration of the nasopharynx, trachea and greater bronchi, especially in patients with airway stenosis and low pulmonary reserve. Double contrast images were obtained with good demonstration of anatomic details and adequate diagnostic value. Visualization of the peripheral bronchi by insufflation was satisfactory only when excessive secretions were not present. The inhalation method was adequate only for visualization of the trachea and main bronchi. The method was found to be safe since diatrizoic acid produced no toxic, allergic or febrile reactions and was given in relatively small amounts without impairment of respiratory function. PMID- 1742129 TI - Ultrasonographic anatomy of veins draining the left lobe of the liver. Feasibility of live related transplantation. AB - The anatomic variations of the left hepatic vein (LHV) in 182 patients with normal liver functions were analyzed using ultrasonography in order to clarify the feasibility of live related hepatic transplantation (LRHT). LHV was demonstrated in 151 patients (83%). Based on the location of the confluence of the middle hepatic vein (MHV) and LHV and the ramifications of the left medial vein (LMV) and the left superior vein (LSV), the livers were classified into 3 types: a) intrahepatic confluence (42/151 livers, 27.8%); b) extrahepatic confluence (69/151 livers, 45.7%); c) separate insertion (40/151 livers, 26.5%); and 23 subtypes. The length of the common trunk and the intrahepatic common trunk of MHV and LHV and the distance from LMV or LSV to the confluence of MHV and LHV were measured. Overall, the control of LHV in situ for LRHT appeared easy in 34/151 patients (22.5%), while in 44/151 patients (29.1%), the length of free LHV and the common trunk was less than optimal for procurement of a left hepatic lobe graft with complete venous outflow and sufficient extraparenchymal length of LHV. PMID- 1742130 TI - Angiographic profile in childhood moyamoya disease. A study of 8 Caucasian Indian children. AB - The cerebral angiograms of 8 patients with childhood moyamoya disease showed that the common findings were stenosis/occlusion of the supraclinoid internal carotid artery and the proximal segments of the anterior and middle cerebral arteries and basal moyamoya. The volume of basal moyamoya and its collateral supply depended upon the stage of the disease. Leptomeningeal collaterals were frequent in the later stages. Stenotic lesions in the posterior circulation were seen in a majority (75%) of patients. A feature unique to the study was evidence of intracranial small-vessel disease and stenotic cervical internal carotid artery in half of the cases. The disease in the ethnic caucasian Indians seems largely similar to the classical disease frequently reported in the Japanese literature. PMID- 1742131 TI - Radiation doses to patients and personnel involved in embolization of intracerebral arteriovenous malformations. AB - Radiation doses to patients and personnel were measured during 5 embolization procedures in 5 different patients. Thermoluminescent dosimeters were used to measure the absorbed doses in different points of the skin of patients as well as personnel. A transmission ionization chamber was used to determine the energy imparted in the patients. The effective dose equivalent HE during the procedures was estimated to be in the range of 6 to 43 mSv to the patients, 10 to 26 microSv to the radiologist in charge of the embolizations, 3 to 24 microSv to the assisting radiographer and 13 to 86 microSv to the nurse anesthetist. Radiation doses to the patients were considerable but the estimated risks from radiation were low compared to the risks of the arteriovenous malformation itself and the hazards of the embolization. The annual radiation doses to the personnel were well below established dose limits. PMID- 1742132 TI - Tissue characterization of intracranial tumors by MR imaging. In vivo evaluation of T1- and T2-relaxation behavior at 1.5 T. AB - The main purpose of this in vivo study was to provide a detailed description of the T1- and T2-relaxation processes in intracranial tumors at 1.5 T. A total of 100 patients were investigated. Optimal experimental conditions were carefully observed, including the use of long TR values. T1 determination was based on a partial saturation inversion recovery sequence covering 12 or 6 data points. T2 determination involved a multiple spin echo sequence with 32 echoes. Calculations included biexponential analysis of the 12-point T1 data and all T2 data obtained. The results were evaluated in accordance with histopathology. The T1- and the T2 relaxation times of the prevailing tumor types were significantly different (p less than 0.0005). However, biologic scatter and overlap between tumor types were considerable. In particular, no discrimination between benign and malignant tumor growth was possible. Biexponential evaluation did not increase the specificity, although a biexponential relaxation behavior was recognized in 37% of the T2 curves. The results indicate that tissue heterogeneity is responsible for most of the scatter in the relaxation times. It is concluded that tissue characterization by MR imaging, based solely on relaxation time measurements, seems to be of no value in the differentiation of intracranial tumors. PMID- 1742133 TI - MR imaging of patellar cartilage degeneration at 0.02 T. Study of 23 cadaveric patellae. AB - MR imaging with a 0.02 T resistive magnet was used to establish the correlation between the histologic grading of patellar cartilage degeneration and fat water separation images or T1- and T2-relaxation times. We examined 23 cadaveric patellae. There was a positive correlation between histologically graded cartilage degeneration and T1-relaxation time. Patellar cartilage was well differentiated from surrounding structures on chemical shift water proton images, and an evaluation of cartilage degeneration was possible. No correlation was found between cartilage damage and T2-relaxation time. Chemical shift imaging at 0.02 T is easy to perform and gives further information of cartilage disorders. PMID- 1742134 TI - Tumor seeding occurring after fine-needle biopsy of abdominal malignancies. AB - Percutaneous fine-needle aspiration biopsy is a commonly used diagnostic procedure with a high accuracy and a low complication rate. However, tumor seeding in the biopsy tracts has been recorded with a frequency of one in 20,000 40,000 biopsies. We report 5 cases of percutaneous tumor seeding recorded after 5,000 fine-needle biopsies of abdominal malignancies at our institution. The risk of implantation metastases induced by fine-needle biopsy warrants consideration in patients with abdominal malignancies since it may compromise the outcome of radical surgery. It should only be performed when the result of the procedure has a direct impact on the choice of therapy. PMID- 1742135 TI - Sclerotherapy for ablation of the gallbladder after gallstone lithotripsy with a mechanical lithotriptor. An experimental study in pigs on the effect of absolute ethanol on edematous gallbladder wall. AB - Chemical ablation of the gallbladder with absolute ethanol following mechanical lithotripsy with the RotoLith lithotriptor was attempted in 10 pigs after open cholecystostomy. Two gallbladders removed immediately after the sclerotherapy demonstrated extensive ulcerations of the mucosa with preserved glands and sinuses under the ulcerations. In 8 gallbladders removed 8 weeks after sclerotherapy a gallbladder remnant with hydrops and/or mucus and more or less intact epithelium was seen in all the pigs. In order to prevent regeneration of epithelium from gallbladder sinuses and glands, more effective sclerosing agents must be found. PMID- 1742136 TI - Effect of indomethacin and salt depletion on renal proton MR imaging. An experimental study in the rat. AB - Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may affect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. PMID- 1742137 TI - Accounting: the dreaded "A" word. PMID- 1742138 TI - An educational model for explaining hospice services. AB - Explaining the concept and philosophy of hospice can be difficult. There is a reluctance in our society to openly address dying/death issues; there is a reluctance on the part of many health-care professionals to look beyond physical issues. The following model has been used successfully to explain hospice to both the general public and health care professionals. It is not intended to introduce hospice to a patient/family during the initial referral/assessment visit. PMID- 1742139 TI - The prevalence and incidence of pressure ulcers in the hospice setting: analysis of two methodologies. AB - Hospice patients may be at greater risk of pressure ulcer development than most patients. This descriptive study explored the prevalence and incidence of pressure ulcers in the hospice setting, utilizing both a prospective and retrospective methodological approach. Levine's theory of the four principles of conservation formed the theoretical basis for the study, and the Braden Scale for Predicting Pressure Ulcer Risk was used for data collection. Prevalence of pressure ulcers was noted to be 13 percent in the study. Incidence of pressure ulcers was found to be zero percent using prospective methodology and 13 percent using retrospective methodology. Five of eight ulcers (62 percent) occurred within two weeks of patient death. Factors related to pressure ulcer development are presented, as well as a discussion of using research methodologies in the hospice setting. The article suggests the need for preventive protocols for skin care for patients who are at risk for pressure ulcer development. PMID- 1742140 TI - Haven Hugs & Bugs. An innovative multiple-family weekend intervention for bereaved children, adolescents and adults. AB - This article describes the development and implementation of a unique, two-day therapeutic program for bereaved families. Issues relevant to program design are presented along with evaluation results. The family focus, the therapeutic value of nature, and the relationship of this program to Multiple Family Therapy, time limited psychotherapy, and wilderness, camping, or recreation therapy approaches are discussed. Questions and suggestions for future evaluation research are noted. The high potential therapeutic and cost-effectiveness of such innovative approaches to bereavement counseling should motivate further program development and outcome research. Information on other weekend bereavement programs is appended. PMID- 1742141 TI - Completing the hospice organizational model. AB - Hospices must be thought of as still being in their formative stages. We need not be satisfied with staffing arrangements and practices that, largely for reasons of expediency and the lack of other models, were inherited from other healthcare agencies or foisted on us by federal bureaucrats and third party payers. These external demands will be countered and features unique to hospices created only to the extent that all of us are clear about what we most need and want for ourselves as staff. That is how we created the patterns used in working with clients. Now let us use the same ingenuity in fashioning ways of working among ourselves. PMID- 1742142 TI - The effects of death education on nurses' attitudes toward caring for terminally ill persons and their families. AB - This study sought to determine the effectiveness of an education program on nurses' attitudes toward caring for terminally ill persons and their family members. The program, based on the hospice concept of care, included a didactic section based on Kubler-Ross' stages of death and dying, and a role-play model designed by the researcher. Data were collected from 34 licensed nurses, aged 18 to 65, practicing in the midwestern United States. The Frommelt Attitude Toward Care of the Dying Scale (FATCOD) was designed by the researcher to assess nurses' attitudes. The FATCOD was found to be a valid and reliable tool. All nurses completed the tool before and after the education program (pre-test, post-test). Compared by a t-test, the scores for the nurses were significantly higher after participation in the educational program. The t-value was found to be 2.97, significant at the less than 0.01 level, 2-tailed probability = 0.006. These findings support the hypothesis that nurses have a more positive attitude toward caring for terminally ill persons and their family members after participation in the program, than the same nurses had before participating in the program. Demographic information including age, years of experience in nursing, highest degree held, basic type of nursing preparation and previous education on death and dying were analyzed to determine their relationship to the nurses' attitudes. The only information which demonstrated any significant relationship to the nurses' attitudes was that of previous education on death and dying. These were computed by an analysis of variance (ANOVA) F = 3.22, F prob = 0.04, significant at less than 0.05 level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742143 TI - Nurses' attitudes toward AIDS patients. PMID- 1742144 TI - Learning health care in the age of AIDS. PMID- 1742145 TI - Tools for autonomy. PMID- 1742146 TI - Amyloidosis: clinical picture, immunological and biomolecular features, treatment prospects. AB - Amyloidosis is the name given to a group of clinically protean diseases whose common feature is the tissue accumulation of amyloid fibrils which have specific optical and staining properties, and are both insoluble in physiological solvents and resistant to proteolytic enzymes. Fibril deposition and progressive extracellular infiltration eventually result in atrophy due to compression. The structure of these fibrils embraces a wide range: immunoglobulin light chain or their fragments, acute phase proteins, hormones, protease inhibitors, beta 2 microglobulin, natriuretic peptides, and proteins whose function is still unknown. Despite this heterogeneity, however, they share a common crystallographic beta-pleated sheet structure. The clinical spectrum includes apparently primary forms, amyloidosis of myeloma, forms secondary to familial Mediterranean fever, Alzheimer's disease, forms associated with type 2 diabetes or medullary carcinoma of the thyroid, inherited-familial amyloidosis, and other less common conditions. Two pathogenetic phases are involved: enhanced production of precursor proteins and their abnormal enzyme cleavage, resulting in the formation of intermediate products corresponding to the amyloid fibrils. The results of treatment are still disappointing: alkylating agents and/or cortico steroids are used in primary forms and for amyloidosis of myeloma; colchicine in familial Mediterranean fever; DMSO in renal amyloidosis; plasmapheresis in inherited-familial forms, together with the supportive management obviously dictated by clinical manifestations. PMID- 1742147 TI - Acute and chronic pancreatitis: an up-date. AB - According to the 1988 Marseilles-Rome classification inflammatory pancreatic diseases are represented by acute (AP) and chronic pancreatitis (CP), pancreatic fibrosis and abscesses (due to infection of cystic cavities). Each form is defined by specific etiological, pathomorphological, functional and evolutive aspects. In our experience with 348 AP cases, gallstones and chronic alcohol abuse, alone or together, represent the major causative factors (over 70% of cases). Mortality observed in necrotizing AP only, varies from 26% of idiopathic to 8% of biliary cases. Ductal scars, exocrine and endocrine impairment were observed in about 45% and 20% respectively as sequelae of necrotizing AP, whatever the etiology. As far as CP is concerned, the main etiological factor is chronic alcohol consumption (82% of cases). The clinical evolution of CP may be roughly divided in two phases, the earlier (within 5 years from onset) characterized by frequently recurrent pain, calcifications and cystic cavities and the later when pain spontaneously regresses and steatorrhea and diabetes tend to appear. Heavy alcohol intake, smoking and frequent relapses are related to a less favourable course. About 60% of the patients underwent surgery within 5 years from onset. Pain relief was achieved in the large majority. Reduction in alcohol intake and the natural tendency of the disease to burn out, probably aid pain relief. Mortality in CP is due to diseases secondary to alcohol and smoking abuse (cardiovascular and neoplastic) more than to CP alone. We believe that multiple parameters are required for a complete definition of each pancreatic patient. PMID- 1742148 TI - The late complications of diabetes mellitus. AB - Late complications of diabetes mellitus include a variety of clinical pictures, mainly related to the involvement of the arterial wall both of large vessels (macroangiopathy) and small vessels (microangiopathy), and of the peripheral nervous system (neuropathy). Their presence in almost all types of diabetes indicates that there is a common pathogenetic mechanism, which can be substantially identified in high blood glucose levels and related alterations. Hyperglycemia, in fact, leads to some metabolic abnormalities, i.e. non-enzymatic glycosylation of proteins and polyol pathway activity; moreover it can negatively affect the pattern of some hormones, especially GH and sex steroids, and normal rheological and clotting properties of blood. These abnormalities, confirmed by experimental models, play a key role in the development of late diabetic complications. However some evidence indicates that a genetic background may predispose to their development or protect from their onset. The two main forms of diabetic retinopathy, non-proliferative and proliferative, show an incidence which increases with age and duration of diabetes, reaching 100% when diabetes lasts for more than 20 years. The risk of blindness, which is very high for the proliferative form, has been dramatically reduced by laser-photocoagulation. Diabetic nephropathy affects a lesser number of diabetics but, after a silent or preclinical stage, leads to renal failure and subsequent replacement therapy. Strict metabolic control in the silent stage and later rigid anti-hypertensive treatment can prevent or retard the evolution of this complication. A close association has been observed between diabetes and hypertension, which can directly affect the onset and evolution of diabetic nephropathy, probably through a common genetic mechanism. Diabetic neuropathy has a wide variety of clinical manifestations, at somatic, autonomic and central levels and can greatly modify the quality and expectancy of life. However, the major cause of death in diabetic subjects is large vessel disease or macroangiopathy, which is similar to non diabetic atherosclerosis regarding the main histopathological and clinical manifestations but has a much higher prevalence and severity. Finally, a specific cardiomyopathy has also been described in diabetes mellitus and can account for the high rate of heart failure observed in these patients. PMID- 1742149 TI - Cardio-respiratory function during sleep. AB - Respiratory function undergoes sleep-associated changes which in normal subjects leave it unaffected. However in some cases they may be more marked than usual or may be superimposed on a pre-existing disease, thus giving rise to sleep-related ventilation disorders. These include obstructive sleep apnea syndrome (OSAS), nocturnal desaturation events of chronic obstructive pulmonary disease (COPD) and restrictive syndromes, as well as nocturnal asthmatic attacks. OSAS is a condition characterized by the frequent recurrence of interruptions of oronasal flow (greater than 10 s.) due to upper airway occlusion induced by a reduction in pharyngeal muscle tone. This phenomenon, particularly prominent in REM sleep, results in oxyhemoglobin desaturation and marked cardiovascular consequences (arrhythmias, increases in pulmonary and systemic arterial pressure), as well as symptoms (loud intermittent snoring, daytime sleepiness, intellectual deterioration etc.). Obesity is often associated with OSAS or may lead to a sleep related hypoventilation syndrome. Treatment is based on weight loss, surgery of upper airway abnormalities, if present, and on splinting of the upper airway by the application of nasal continuous positive airway pressure. In COPD and restrictive disorders, nocturnal hypoxemia is mainly due to REM-associated loss of respiratory muscle tone, as well as in the sleep-related exaggeration of functional defects due to COPD (low chemoreceptor sensitivity, high closing volume etc.). Treatment is based on oxygen administration, provided that possible side-effects are carefully monitored. Nocturnal asthma is due to circadian changes in hormonal secretion (catecholamines, cortisol), as well as supine posture, reduced muco-ciliary clearance, gastro-esophageal reflux etc. Sleep itself plays some role through a depressed arousal reaction in slow wave sleep, resulting in more marked and prolonged attacks in this stage. Slow-release theophylline or beta-mimetic medications, as well as new chromones and antimuscarinic drugs are therapeutic alternatives. PMID- 1742150 TI - Ascites in liver diseases. AB - The clinical course of patients with cirrhosis of the liver is frequently complicated by progressive impairment of renal sodium handling leading to the formation of ascites. The occurrence of ascites is generally accompanied by the activation of several hormones and intrarenal autacoids and a complex derangement of systemic, portal and renal hemodynamics. The earliest "underfilling" theory of sodium retention proposes that ascites formation leads to hypovolemia and secondary sodium retention. According to the "overflow" theory, ascites formation is a secondary event with respect to sodium retention, which occurs as a primary phenomenon in the absence of hypovolemia. A third recently developed theory suggests that peripheral arteriolar vasodilation is the primary event of intravascular underfilling. The major documented site involved in arteriolar vasodilation is the splanchnic circulation. Occurrence of underfilling is not related to a reduction of plasma volume but to the enlargement of the vascular compartment. Vascular underfilling triggers a series of hemodynamic and hormonal compensatory events such as an increase in cardiac output and plasma volume, activation of the renin-angiotensin-aldosterone and sympathetic nervous system and non-osmotic hypersecretion of antidiuretic hormone and sodium retention, all of which aim at refilling the vascular compartment. In patients with compensated cirrhosis, i.e. without ascites, compensatory events maintain blood volume despite vascular underfilling, and so these patients do not develop ascites. In patients with decompensated cirrhosis, vascular underfilling due to arterial vasodilation, together with a reduced oncotic pressure and a severe degree of portal hypertension, favours the development of ascites. Underfilling of the arterial circulation is at its maximum in functional renal failure and the hepatorenal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742151 TI - The application of the theory of systems in internal medicine. State of the art and perspectives. AB - The application and contribution of Cartesian methodology to the development of medicine in physiology, pathophysiology and therapy have been overwhelming. The accumulation of knowledge over the last 3 centuries in scientific research is largely attributed to Cartesian methodology. This method, which in the past was used for the acquisition of nosological data is no longer sufficient for the interpretation of complex phenomena which modern science nowadays requires. The solution to these complex problems is only possible by means of the application of the theory of systems especially for the functional evaluation of biological feedback. PMID- 1742152 TI - Lymphoproliferative diseases of uncertain classification. AB - In spite of the recent progress in the biology and histogenesis of the lymphoproliferative diseases, many doubts still remain about their possible evolution. On the one hand, many cases have been studied showing a benign course in spite of a typical monoclonal phenotype; on the other, some clinically aggressive forms of lymphoproliferation prove to be polyclonal throughout their course, even when checked with highly sophisticated techniques. In this article we have reviewed, in both clinical and etiopathogenetic terms, the classification of these processes in the light of the new findings provided by extensive use of the most advanced investigational techniques of genotype and phenotype analysis. We have recognized three main groups of lymphoproliferative disorders of uncertain significance, based on pathophysiological, anatomical and developmental considerations: 1) lymphoproliferative diseases that take place on a background of either congenital or acquired immunodeficiency, referred to as "opportunistic lymphoproliferative disorders"; 2) lymphoproliferative diseases deriving from "mucosa associated lymphoid tissue" (MALT); 3) lymphoproliferative diseases of uncertain histogenesis, now classified as "T lymphomas". The opportunistic lymphoproliferative disorders, particularly in HIV+ patients and transplant recipients, often show developmental and etiopathogenetic features which may help to elucidate their natural history. Frequent involvement of Epstein-Barr virus and the related host's immune response patterns provide powerful tools to outline the alternative developmental pathways of such disorders.2+ Worthy of note is acute infectious mononucleosis which, though self-limiting when occurring in the immunocompetent host, may be considered as a lymphoproliferative process and sometimes shows some "aggressive'' morphological aspects. Special attention is paid to the obscure origin of Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742153 TI - Role of the endothelium in controlling local blood flow. AB - During this last decade it has been widely recognized that the vascular endothelium reacts to mechanical force as well as to various neurohumoral mediators by releasing vasodilator and/or vasoconstrictor substances, and thus contributes to the relaxation of local blood vessels and the control of local circulation. In addition, substances produced and released by endothelial cells play a major role in controlling platelet-endothelium interaction and platelet aggregation. The endothelium may contribute to the local control of vascular tone by secreting prostacyclin, endothelium-derived relaxing factor(s) (EDRF) or endothelium derived contracting factor(s) (EDCF). Prostacyclin, a major metabolite of the cyclo-oxygenase pathway in the vascular endothelium and the subject of intense studies since its discovery in 1976, has been reviewed many times and will therefore not be discussed in this report. We will focus on other recently described endothelium-dependent vasoactive mediators, particularly EDRF and EDCF. PMID- 1742154 TI - Diuresis and intensive saluresis. AB - Intensive saluresis, intended as an exceptional though real and practicable therapeutic approach, has made unimaginable progress possible in different sectors of Internal Medicine relating to hydrosaline balance alterations such as chronic and acute renal failure, nephrosic syndrome, refractory heart failure, acute pulmonary edema and ascites. We are proud to be the first who followed a path that assured patients compensation beyond "classic" therapeutic possibilities, and undoubtedly better quality of life, as well. PMID- 1742155 TI - Pathogenetic aspects of allergic respiratory syndromes. AB - Over the past twenty years great research effort has been made to clarify the pathogenetic mechanisms of allergic rhinitis (AR) and bronchial asthma (BA). The discovery of two types of Fc epsilon receptors (Fc epsilon RI and Fc epsilon RII) has made it possible to understand that allergic reactions can be due to interactions between allergens and cytophilic IgE bound not only by mast cells and basophils, but also by macrophages, lymphocytes, eosinophils and platelets. Knowledge of the complex mechanisms which regulate IgE antibody production has substantially improved since it was shown that IL-4 and T/B cell interactions are essential for the induction of human IgE synthesis, whereas IFN-gamma plays a negative regulatory role. In mice and humans, two types of helper T cells (Th1 and Th2) have been recognized, they produce different cytokines resulting in both cross-regulation of T cell function and B cell activity. In view of their particular pattern of cytokine secretion, Th2-type cells would be important in the specific response to allergens and in allergic inflammation. New knowledge about the mechanisms involved in the effector phase of allergic reactions and respiratory tract inflammation has recently been gained. In particular, the discovery of a complex network among cytokines, mediators and neuropeptides has offered the opportunity for advancing a new, integrative view of how the pathophysiological alterations responsible for respiratory allergic syndromes come about. We now realize that late phase allergic reactions, chronic allergic inflammation and tissue hyperreactivity are induced and maintained by a complex inflammatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742156 TI - A statistical approach to computerized EEG: preliminary data on control subjects and epileptic patients. AB - Factor Analysis represents an important method of extracting salient features from EEG data condensing functional as well as spatial informations in a few factors and so reducing redundancy of multi-channels computerized EEG data. A 16 channel computerized frequency analysis of background brain electrical activity during 3 functional conditions (eyes closed, eyes open and hyperventilation) were performed in 2 groups, 50 healthy subjects and 14 epileptic patients with generalized seizures. The differences in each frequency band between the 2 groups have been assessed by means of factor scores. Factor scores differences between control and epileptic patients have been found in theta and alpha frequency bands. These interictal EEG abnormalities were more evident in epileptic patients. This preliminary study shows the confirmatory capability of Factor Analysis and its usefulness in managing and comparing computerized EEG data. PMID- 1742157 TI - Topographic component (parallel factor) analysis of multichannel evoked potentials: practical issues in trilinear spatiotemporal decomposition. AB - We describe a substantive application of the trilinear topographic components/parallel factors model (TC/PARAFAC, due to Mocks/Harshman) to the decomposition of multichannel evoked potentials (MEP's). We provide practical guidelines and procedures for applying PARAFAC methodology to MEP decomposition. Specifically, we apply techniques of data preprocessing, orthogonality constraints, and validation of solutions in a complete TC analysis, for the first time using actual MEP data. The TC model is shown to be superior to the traditional bilinear principal components model in terms of data reduction, confirming the advantage of the TC model's added assumptions. The model is then shown to provide a unique spatiotemporal decomposition that is reproducible in different subject groups. The components are shown to be consistent with spatial/temporal features evident in the data, except for an artificial component resulting from latency jitter. Subject scores on this component are shown to reflect peak latencies in the data, suggesting a new aspect to statistical analyses based on subject scores. In general, the results support the conclusion that the TC model is a promising alternative to principal components for data reduction and analysis of MEP's. PMID- 1742158 TI - Accurate matching of electromagnetic dipole data with CT and MR images. AB - Interpretation of EEG (electroencephalography) or MEG (magnetoencephalography) derived three-dimensional dipole localizations is hampered by poor visualization. This paper describes a method for combining dipole data with structural image data of the same patient. To ensure high precision this method utilizes external markers that are easy to apply. These markers can achieve subslice accuracy and can even be used to pinpoint reference points outside the scanned volume. Accurate matching is thus provided even in standard imaging protocols employing thick slices and/or large interslice gaps. The results of the matching method are presented in 2D and 3D visualizations. The hybrid images facilitate the interpretation of dipole localizations with respect to the patient's anatomy. PMID- 1742159 TI - Brain activity associated with skilled finger movements: multichannel magnetic recordings. AB - We recorded with a 24-channel SQUID magnetometer cerebral activity preceding and following self-paced voluntary 'skilled' movements in four healthy adults. The subject pressed buttons successively with the right index and middle fingers aiming at a time difference of 40-60 ms; on-line feedback on performance was given after each movement. Slow magnetic readiness fields (RFs) preceded the movements by 0.5 s and culminated about 20 ms after the electromyogram (EMG) onset. Movement-evoked fields, MEFs, opposite in polarity to RFs, were observed 90-120 ms after the EMG onset. They were followed by an additional 'skilled performance field', SPF, 400-500 ms after the EMG onset. The source locations of RF, MEF, and SPF were within 2 cm from sources of the somatosensory evoked responses, which were situated in the posterior wall of the Rolandic fissure; the sources of MEF were closest to the midline. Neural generators of these deflections and of the corresponding electric potentials are discussed. PMID- 1742160 TI - The value of EEG-mapping in focal cerebral lesions. AB - In 148 patients with focal cerebral lesions the findings of EEG mapping, routine EEG and CT were compared. Regarding etiology 43 patients suffered from completed stroke (CS), 43 patients from transient ischemic attack (TIA), 33 patients had an intracerebral hemorrhage (ICH) and 29 an hemispheric tumor. In 37 patients with CS (86%) and 27 patients with TIA (63%) the EEG mapping revealed focal changes, but only in 28 patients with CS (65%) and in 11 patients (26%) with TIA using routine EEG alone. Thus the EEG mapping showed focal abnormalities significantly more often. In the remaining patient groups no significant difference in the results of EEG mapping or routine EEG could be demonstrated. Focal abnormalities corresponding to focal lesions seen in CT were obtained by means of EEG mapping in 27 patients (90%) with CS and 10 patients (77%) with TIA, but only in 17 patients (57%) with CS and 4 patients (31%) with TIA using routine EEG and in that way the EEG mapping could indicate focal lesions in CT significantly more often than routine EEG. In the remaining patient groups no significant difference in the number of focal changes corresponding to lesions in CT could be seen. PMID- 1742162 TI - The effect of ethidium bromide on the liquid crystalline phases of aqueous DNA. AB - The influence of the intercalation of ethidium bromide (EB) on the characteristics of the DNA cholesteric and hexagonal mesophases is studied by optical microscopy, circular dichroism, and X-ray diffraction. The distance between DNA rods in the hexagonal phase is not modified by the presence of EB whereas the pitch of the cholesteric mesophase is considerably shortened by the dye. This seems to be related to the stereochemical effect of the intercalation rather than to the presence of a random distribution of the positive charge of the dye. PMID- 1742161 TI - Spatial mapping of SEP in comatose patients: improved outcome prediction by combined parietal N20 and frontal N30 analysis. AB - The aim of this study is to evaluate whether SEP spatial mapping can improve outcome prediction in comparison to the conventional SEP recordings. Twenty patients comatose as a result of head injury or cerebral vascular disorders were submitted to 19-channel SEP mapping from median nerve stimulation. SEP recording were performed within the 4th hospital day in 18 cases and over one month from the insult in the remaining two. Nine patients (45%) showed a good recovery or a mild disability, 3 (15%) a severe disability and the rest (40%) died or remained in a vegetative state. Five patients (28%) had bilaterally normal SEP, 5 (28%) the absence of both parietal N20 and frontal N30, while the others (44%) had a dissociation N20/N30 (namely, preserved N20 with absent N30). The SEP mapping was significantly related to the outcome (P = 0.0087) and improved the outcome prediction in comparison to the conventional SEP recordings, allowing to check the presence of frontal N30: in patients with bilaterally present N20 the outcome appeared to depend upon the N30. SEP mapping proved to be a far superior prognostic indicator than the Glasgow Coma Scale. In 3 patients with midline shift on CT scan an abnormal spatial distribution of N20 was disclosed by SEP mapping. Our preliminary results suggest that SEP mapping may improve the assessment of comatose patients in comparison to the use of parietal derivations only. PMID- 1742163 TI - The circular dichroism of tumor necrosis factor-alpha: measurement into the vacuum UV and analysis for secondary structure. AB - The circular dichroism (CD) spectrum of tumor necrosis factor-alpha has been measured into the vacuum UV to 168 nm. Analysis of the CD for secondary structure is in good agreement with X-ray diffraction results, but the analysis is somewhat unstable. Adding the CD of this protein together with its X-ray determined secondary structure to the basis set should improve subsequent analyses of CD spectra for other all-beta proteins. PMID- 1742164 TI - Absolute configuration for peptidomimetic residues in bioactive peptides. AB - A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1H-NMR parameters in solution. Four peptide systems incorporating either retro-inverso modifications or 2 aminocyclopentanecarboxylic acid (2-Ac5c) as a peptidomimetic for proline are discussed. (1) Two 14-membered cyclic dermorphin analogs Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem-diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar6-(S and R)-mPhe7-D Trp8-Lys9-Thr10-Phe11], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gemdiamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2 Ac5c [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c,cis-(1R,2S)-2-Ac5c, and cis (1S,2R)-2-Ac5c] in place of proline c[(2-Ac5c)6-Phe7-D-Trp8-Lys9-Thr10-Phe11]. (4) Morphiceptin related analogs incorporating a cis-2-Ac5c residue as shown in Tyr-cis-2-Ac5c-Phe-Val-NH2. The methodology described in this investigation could be applied to a wide variety of peptide systems. PMID- 1742165 TI - Polypeptide models of elastin: CD and NMR studies on synthetic poly(X-Gly-Gly). AB - Poly(X-Gly-Gly), simple structural models for the hydrophobic, proline-devoid, regions of elastin, have been synthesized and studied by circular dichroism and NMR spectroscopies. The results gave evidence of type II beta-turns as the only ordered structure present in the polymers. The stability of the turns has been shown to decrease on hydration and to increase in the series Leu less than Ala less than Val less than Ile. PMID- 1742166 TI - The asymmetric hydroformylation in the synthesis of pharmaceuticals. AB - The asymmetric hydroformylation reaction represents a potential powerful synthetic tool for the preparation of large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutic activity. Essential and nonessential amino acids, 2-arylpropanoic acids, aryloxypropyl- and beta-phenylpropylamines, modified beta-phenylethylamines, pheniramines, and other classes of pharmaceuticals are available through enantioselective oxo-reaction of appropriate functionalized olefins; this process is catalyzed by rhodium or platinum complexes with chiral ligands, mainly chelating phosphines, and sometimes affords very high enantiomeric excesses. Furthermore, the application of many simple optically active aldehydes arising from asymmetric hydroformylation as chiral building blocks for the synthesis of complex pharmacologically active molecules such as antibiotics, peptides, antitumor macrocycle compounds, and prostaglandins is conveniently emphasized. The possibility of a future application of this asymmetric process for the production of many synthons to obtain other valuable pharmaceuticals is widely discussed too. PMID- 1742167 TI - Heat shock induces thermotolerance and inhibition of lysis in a lysogenic strain of Lactococcus lactis. AB - In this preliminary work, the heat shock response of lactic acid bacteria was investigated and characterized. Log-phase Lactococcus lactis cells pre-incubated at 40 degrees C before heat challenge at 52 degrees C for 30 min demonstrated increased thermotolerance as compared with cells pre-incubated at 30 degrees C. The response persisted for at least 60 min. Additionally, we demonstrated that: (i) the physiological expression of the heat shock response is temperature dependent; (ii) ethanol 4.0% (v/v) caused, to a lesser extent, a response similar to the heat shock; and (iii) hydrogen peroxide failed to induce a detectable response. Furthermore, we suggest that the induction of the heat shock response increases the resistance of a lysogenic strain of L. lactis, treated by mitomycin C (1.25 micrograms/ml), to lysis by the bacteriophage. PMID- 1742168 TI - Immunomagnetic separation of Salmonella from foods. AB - Salmonella could be separated from different inoculated foods using antibody coated immunomagnetic beads. When applied on suitable foods, the immunomagnetic separation technique showed a sensitivity of 10-20 Salmonella cells/g of the original sample. The technology appeared less useful for some food items. PMID- 1742169 TI - Production of staphylococcal enterotoxin D in foods by low-enterotoxin-producing staphylococci. AB - The goal of this investigation was to determine whether staphylococcal strains producing enterotoxins at nanogram levels per milliliter in laboratory medium, not detectable by gel diffusion methods, could produce sufficient enterotoxin in foods to result in food poisoning. Three low-enterotoxin D (SED)-producing strains were selected for this research because this enterotoxin is produced in smaller amounts than the other enterotoxins. The foods used were cream pie and cooked ham, divided into two portions, sterile and non-sterile. Each portion was inoculated with known concentrations of the staphylococcal strains under study and incubated for 48 h at 25, 30, and 37 degrees C. Samples were taken after 24 and 48 h. Enterotoxin was detectable in both sterilized and unsterilized cream and ham after 24 h at 37 degrees C with an inoculum of 10(3)/g. Some strains produced detectable amounts of enterotoxin in the sterilized foods after 24 h at 30 degrees C and some produced detectable amounts of enterotoxin in the sterilized foods after 24 h at 25 degrees C with inocula of 10(4)/g. It can be concluded that staphylococcal strains producing enterotoxin at ng/ml levels in laboratory medium, not detectable by gel diffusion methods, can produce sufficient enterotoxin (ng/g) in foods to cause food poisoning. PMID- 1742170 TI - Assessment of the hygienic adequacy of a commercial hot boning process for beef by a temperature function integration technique. AB - The hygienic performance of a commercial hot boning process for beef carcasses was assessed by a temperature function integration technique. The potential proliferation of Escherichia coli was calculated from 50 temperature histories for the persistently warmest, microbially contaminated regions of product passing through both the carcass cutting and carton cooling phases of the process. The maximum calculated proliferation was similar to, but the average proliferation was more than, the respective values previously obtained for a beef side cooling process that complied with Good Manufacturing Practice. After upgrading of the carton cooling facility the process was re-assessed. Then, for a sample of 50 temperature histories, the maximum proliferation was less than, and the average proliferation was similar to, the respective values for the side cooling process. Observed proliferations of E. coli inocula in cooling cartons of product were compared with the proliferations calculated from temperature histories obtained from sites close to inocula. The pairs of calculated and observed values mostly agree within +/- 1 generation. PMID- 1742171 TI - Application of polymyxin-coated polyester cloth to the semi-quantitation of Salmonella in processed foods. AB - A rapid and economical semi-quantitative test for Salmonella cells in foods is proposed. Food samples containing different levels of Salmonella cells were homogenized and serially diluted in enrichment broths and then incubated for about 20 h at 37 degrees C. The presence of Salmonella cells in each dilution was assayed by capturing deoxycholate-extracted Salmonella lipopolysaccharides on a sheet of polymyxin-coated polyester cloth, followed by colorimetric detection with an anti-Salmonella antibody-enzyme conjugate. The minimum dilutions which resulted in no detectable growth were correlated with the extent of Salmonella contamination in the food samples. PMID- 1742172 TI - Comparison between semisolid Rappaport and modified semisolid Rappaport Vassiliadis media for the isolation of Salmonella spp. from foods and feeds. AB - Two semisolid media poured in petri dishes, semisolid Rappaport and modified semisolid Rappaport Vassiliadis were compared for the recovery of Salmonella spp. from 154 high- and low-moisture foods and feeds. Semisolid media were inoculated after pre-enrichment in buffered peptone water and after enrichment in Muller Kauffmann tetrathionate broth and selenite cystine broth. Also a conventional procedure was used, where the enrichment broths were streaked on Brilliant Green and bismuth sulphite agars. Of 62 samples found positive for Salmonella by one or more methods, semisolid Rappaport detected all of them and 60 when inoculated directly from the pre-enrichment broth. Modified semisolid Rappaport-Vassiliadis gave only 20 positive samples. The difference in productivity between semisolid Rappaport and the other media poured in plates (modified semisolid Rappaport Vassiliadis, Brilliant Green and bismuth sulphite agar) was statistically significant (P less than 0.001). The incubation temperature recommended for modified semisolid Rappaport-Vassiliadis (42 degrees C) was found to be too high. By comparison to the other media, semisolid Rappaport gave a 500% increase in the detection of the enteritidis serotype of Salmonella. PMID- 1742173 TI - Temperature in agar plates and its influence on the results of quantitative microbiological food analyses. AB - The numbers of colony forming units (cfu) of some strains of Enterobacteriaceae growing in Violet Red bile agar at 44 degrees C can vary considerably depending on incubation conditions and location of an individual agar plate in a stack. The reason is that the heating-up rates of the agar in plates incubated at elevated temperatures are slower if the incubators do not have an air circulator and/or if the plates are located in the centre of a stack. Variability in agar temperatures among different plates after 24 h of incubation at 44 degrees C was higher if plates were placed in an incubator with an air circulator than in an incubator without one. This effect could be avoided if the plates were incubated enclosed in a plastic bag. PMID- 1742174 TI - The effect of microwave and conventional cooking on the temperature profiles and microbial flora of minced beef. AB - Beef mince samples were cooked to the rare, medium and well done states by microwave and conventional oven methods. The raw samples all contained large numbers of contaminating organisms and low numbers of Listeria monocytogenes were detected in the majority of samples. A substantial proportion of the contaminating flora survived in mince cooked by microwaves to the rare, medium and well done states, prior to a 30-min standing period. Listeria monocytogenes survived in all samples cooked by microwaves to the rare state, prior to the standing period and was still present in one of three after the standing period. It was also detected in one of three samples cooked to medium prior to a standing period. This organism was not detected in mince cooked by conventional oven methods. In all the samples cooked by microwaves with a standing period and samples cooked to rare and medium by conventional oven, survival of some of the microflora occurred. The survival rate decreased with the severity of the cooking treatment. PMID- 1742175 TI - The effects of temperature, pH, sodium chloride and sodium nitrite on the growth of Listeria monocytogenes. AB - An automated turbidimetric system using multiwelled plates was used to examine the effects of different combinations of NaCl (0.5-8.0% w/v), NaNO2 (0-400 micrograms/ml) pH (4.6-7.4) and temperature (5-30 degrees C) on the growth of Listeria monocytogenes in tryptone soya broth. The data presented clearly illustrate the combinations that permit visible growth of the organism. The ability of L. monocytogenes to grow at low pH levels was strongly influenced by incubation temperature as well as NaNO2 concentration. At 20 degrees C and below, no visible growth was detected, even with 50 micrograms/ml NaNO2 at pH 5.3 (or below) within 21 days. At pH 6.0 and above, NaNO2 had little effect in delaying visible growth except at higher concentrations and also at lower incubation temperatures. PMID- 1742176 TI - Primary erythrocytosis in childhood. PMID- 1742177 TI - Fosfomycin--friend or foe? PMID- 1742178 TI - Primary immunodeficiencies: milestones in the history of pediatric immunology. AB - Pediatric immunology is a recent and important branch of pediatrics. Besides development of vaccines, the discovery of primary immunodeficiencies has represented a major contribution in the history of pediatric immunology. Characterization of these disorders as inborn errors of immunity has been crucial for understanding the functional organization and ontogeny of the immune system. Thus, progress in the study of immunodeficiency diseases has contributed to progress in pediatric immunology as a whole. As a result of these advances and a major biotechnology breakthrough, new therapeutic strategies have been devised. The benefits of these strategies extend far beyond the area of immunodeficiencies; they permit better care of infants and give new therapeutic approaches to other inherited disorders. PMID- 1742179 TI - A disseminated alveolar rhabdomyosarcoma in a 9-year-old boy disclosed by chromosomal translocation (2;13) (q35;q14) AB - A 9-year-old boy presented with a small subcutaneous tumor of the trunk and diffuse bone marrow involvement. The first histological diagnosis given was undifferentiated malignancy possibly of neural crest origin and chemotherapy was started immediately using vincristine, cyclophosphamide, cisplatin, and teniposide (OPEC). Complete response was achieved after four courses of chemotherapy. Histological slides were then reviewed and the final diagnosis of alveolar rhabdomyosarcoma (RMS) was retained. Moreover, chromosome analysis of malignant cells in the bone marrow revealed a translocation involving chromosomes 2 and 13:t(2;13) (q35;q14). This specific karyotype finding has been recently reported in a few cases and could be specific for alveolar RMS. The patient had a relapse 7 months after diagnosis and died 4 months later. PMID- 1742180 TI - Primary benign erythrocytosis with high erythropoietin levels and an early erythropoietin-sensitive population in the peripheral blood. AB - Primary erythrocytosis diagnosed in a 10-month-old female and followed for 12 years is described. The erythrocytosis was associated with an abnormally elevated set point of erythropoietin production in which the sensitivity fluctuated independently, but corresponded to the alterations in the oxygen-carrying capacity of the blood, when the hematocrit was lowered by phlebotomies. Extensive work for secondary erythrocytoses failed to demonstrate a recognizable cause for this abnormal erythropoietin production. Erythroid cell cultures from peripheral blood mononuclear cells showed the existence of at least two populations: one consistent with dramatic expansion of the erythron in keeping with enhanced sensitivity to endogenous erythropoietin, and the other consistent with the features of typical colonies derived from burst-forming units-erythroid (BFU-Es), seen in normal peripheral blood on days 12 to 14 of culture. The expanded population was characterized by the appearance of single colonies on days 4 to 6 and enormous response to the increasing amounts of erythropoietin, which enhanced their number, size, and maturation. The combination of clinical and in vitro data as well as the absence of any abnormality in the erythropoiesis of the parents and sibling suggest that the erythrocytosis in this child represents a new form with a benign course. PMID- 1742181 TI - Diabetes insipidus 9 years after cessation of therapy for acute lymphoblastic leukemia. AB - A case of a 16-year-old who developed diabetes insipidus (DI) 9 years after cessation of therapy for ALL is reported. Because hereditary and traumatic factors are excluded as a cause of DI in this patient, possible explanations may be leukemic CNS relapse, secondary brain tumor, primitive idiopathic DI, and late sequelae of CNS radiochemotherapy. PMID- 1742182 TI - Leiomyoma of the suprarenal gland in a child with ataxia-telangiectasia. AB - We report the occurrence of a leiomyoma of the suprarenal gland in a 10-year-old girl with ataxia-telangiectasia (A-T). Muscle cell tumors are very uncommon in this gland as they are in A-T. Possible reasons for developing nonhematologic tumors in this syndrome are reviewed. A defect in DNA repair mechanisms probably favors, in young children, the expression of tumors normally expected in the aged. PMID- 1742183 TI - Fosfomycin does not reduce cytostatic activity of cis-platinum against human osteosarcoma cell lines in vitro. AB - Fosfomycin has been shown to ameliorate the dose-limiting ototoxicity and nephrotoxicity associated with the antineoplastic agent cis-platinum. Clinical use of fosfomycin in cis-platinum-treated tumor patients critically depends on retaining therapeutic efficacy of cis-platinum while designing modalities to reduce side effects. This study uses two independent assay systems for cell viability and proliferation; we demonstrate that cytocidal activity of cis platinum against human osteosarcoma cell lines is not affected by various concentrations of fosfomycin up to 0.1 mg/ml in vitro. This suggests that in these cells there is no direct pharmacodynamic interaction of cis-platinum and fosfomycin with respect to mechanisms crucial for tumor kill. PMID- 1742184 TI - Cell-mediated immunity in children with Hodgkin's and non-Hodgkin's lymphomas. AB - Natural killer (NK) cell activity and lymphocyte proliferation to mitogens might to have diagnostic implications that will help to distinguish between benign and malignant lymphadenopathy in children. In addition, we suggest that NK activity and especially the lowering of NK activity after chemotherapy might be of prognostic value in NHL children. PMID- 1742185 TI - Reversible changes on computed tomography scans of the brain during induction therapy for acute lymphoblastic leukemia in children. AB - Children with acute lymphoblastic leukemia (ALL) have been shown to develop changes on computed tomography (CT) scans of the brain. These changes are seen both during and after therapy. Some of the results have been contradictory. Nine children with ALL were examined by CT of the brain during induction therapy. All children showed normal CT scans on the day of diagnosis. One month later all had dilatation of the ventricles and widened sulci. During the next 9 months the CT scans gradually were normalized. We conclude that such changes in CT scans of the brain are transitory and are caused by the high dose of prednisolone administered during induction therapy. PMID- 1742186 TI - Isolated muscular relapse in a child with B-acute lymphoblastic leukemia, off therapy. PMID- 1742187 TI - Clostridium difficile in children with malignant disease. PMID- 1742188 TI - Interleukin-6 and thrombocytopoiesis: probable role of platelets during acute phase responses. PMID- 1742189 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 1 June 1991. PMID- 1742191 TI - Outbreaks of rubella in Amish communities, 1991. PMID- 1742190 TI - Rabies. Implications of the Channel Tunnel for the United Kingdom's freedom from rabies. PMID- 1742192 TI - Cholera in Africa. PMID- 1742193 TI - Measles surveillance. 1982-1990. PMID- 1742194 TI - Hepatitis A. PMID- 1742195 TI - Fourth report of the cooperative, open-ended study of slowly growing mycobacteria by the International Working Group on Mycobacterial Taxonomy. AB - The open-ended study of the International Working Group on Mycobacterial Taxonomy is an ongoing project to characterize slowly growing strains of mycobacteria that do not belong to well-established or thoroughly characterized species. In this fourth report we describe two numerical taxonomic clusters that represent subspecies or biovars of Mycobacterium simiae, one cluster that encompasses the erstwhile type strain of the presently invalid species "Mycobacterium paraffinicum," one cluster that is phenotypically very similar to Mycobacterium avium and Mycobacterium intracellulare but may be a separate genospecies, one cluster that appears to be phenotypically distinct from M. avium but reacts with a nucleic acid probe specific for M. avium, and three tentatively defined clusters in proximity to a cluster that encompasses the type strain of Mycobacterium malmoense. Of special practical interest is the fact that one of the latter three clusters is composed of clinically significant scotochromogenic bacteria that can be misidentified as the nonpathogenic organism Mycobacterium gordonae if insufficient biochemical tests are performed. PMID- 1742196 TI - Numerical analysis and DNA base compositions of some thermophilic Bacillus species. AB - Morphological, physiological, and biochemical characteristics and the DNA base compositions of 133 thermophilic Bacillus strains were determined. A total of 54 of these strains were received as identified species (mainly Bacillus stearothermophilus, Bacillus coagulans, Bacillus brevis, and Bacillus licheniformis) from international culture collections, and 79 newly isolated strains, which were isolated mainly from sugar diffusion juices of Italian plants, were also examined. Numerical taxonomy techniques (simple matching coefficient and unweight pair grouping using the mathematical average) and DNA G + C values showed that the strains aggregated into nine clusters. Both B. licheniformis and B. brevis were well separated from the other organisms. B. stearothermophilus and B. coagulans were confirmed as separate clusters and exhibited greater heterogeneity than previously shown. The B. stearothermophilus strains clustered into four groups, three of which have been recognized previously by other authors; the members of the fourth group had distinctive characteristics, including considerable biochemical inertness, an inability to grow at temperatures greater than 60 degrees C, and a high G + C content. Within the B. coagulans cluster the strains with characteristics very similar to those of the new species Bacillus smithii clustered together. However, the remaining strains were still clearly separated into two groups; one of these groups was considered B. coagulans sensu stricto, and the other was distinguished by morphological and biochemical criteria, such as spores which do not swell the sporangia, utilization of citrate, a higher proteolytic activity, and acidification of some carbohydrates. Our results were confirmed by comparing them with distinctive characteristics of recently described thermophilic Bacillus species. PMID- 1742197 TI - Bacillus brevis Migula 1900 taxonomy: reassociation and base composition of DNA. AB - Of 87 strains previously identified as Bacillus brevis Migula 1900, 58 had G + C contents of 47.0 to 51.9 mol%, a range that included the G + C content (48.7 mol%) of the type strain. The G + C contents for three other groups consisting of 5, 7, and 17 strains were 37.0 to 41.9, 42.0 to 46.9, and 52.0 mol% or higher, respectively. DNA reassociation studies showed that 25 of the 58 strains with G + C contents of 47.0 to 51.9 mol% were closely related genetically to the type strain and to each other. For the most part, this genetically related group was phenotypically homogeneous; variations in the fermentation of mannitol and mannose were observed. My results strongly suggest that many of the strains were misclassified as B. brevis. Consequently, much of the phenotypic heterogeneity of the species B. brevis Migula 1900 is not due to variations exhibited by genetically related organisms, but is the result of variability introduced by the presence of genetically unrelated strains. PMID- 1742198 TI - Evaluation of the genus Listonella and reassignment of Listonella damsela (Love et al.) MacDonell and Colwell to the genus Photobacterium as Photobacterium damsela comb. nov. with an emended description. AB - The genus Listonella, which was recently described on the basis of 5S rRNA sequence data, was found to be of dubious value on the basis of the results of a comparison of a number of taxonomic studies involving members of the Vibrionaceae. The available data suggest that 5S rRNA sequences may be of limited taxonomic use at the intra- and intergeneric levels, at least for apparently recently evolved groups, such as the Vibrionaceae. In this light, we assessed the generic assignment of the species Listonella damsela. Phenotypic characterization of 12 strains of bacteria assigned to L. damsela, including type strain ATCC 33539, revealed a strong resemblance to members of the genus Photobacterium. All of the strains conformed to major characteristics common to all known Photobacterium species. The characteristics of these organisms included the absence of a flagellar sheath and accumulation of poly-beta-hydroxybutyrate during growth on glucose coupled with the inability to utilize DL-beta hydroxybutyrate as a sole carbon source. On the basis of the phenotypic data, we propose that L. damsela should be reassigned to the genus Photobacterium as Photobacterium damsela comb. nov. PMID- 1742199 TI - Streptococcus crista sp. nov., a viridans streptococcus with tufted fibrils, isolated from the human oral cavity and throat. AB - We studied strains of an unusual streptococcus that superficially resembles Streptococcus sanguis but has fibrils that are arranged in lateral tufts. These strains were originally isolated from human throats and oral cavities and have been referred to previously as "Streptococcus sanguis I," the "CR group," and the "tufted-fibril group." Until now, insufficient phenotypic data have been available to allow reliable differentiation of these strains from other viridans streptococcal species, particularly the species in the S. sanguis group. Recently, workers have proposed a scheme of phenetic tests that is based on 4 methylumbelliferyl-linked substrates and conventional biochemical tests and allows the tufted-fibril group to be differentiated; these organisms differ from other viridans species in being able to hydrolyze arginine but not esculin and in producing alpha-L-fucosidase but not beta-glucosidase or alkaline phosphatase. These data, together with the results of our DNA-DNA hybridization experiments and the unusual ultrastructure of the tufted-fibril strains as determined by electron microscopy, demonstrate that these organisms represent a new species, for which the name Streptococcus crista is proposed. The DNA base composition is 42.6 to 43.2 mol% G + C. The type strain is strain CR311 (= NCTC 12479). PMID- 1742200 TI - Phenotypic differentiation of bifidobacteria of human and animal origins. AB - The phenotypes of 153 strains belonging or related to the genus Bifidobacterium were studied. These organisms included 38 collection strains and 115 wild strains (41 strains of human origin, 56 strains of animal origin, and 18 strains obtained from rivers or sewage). Our phenotypic analysis revealed seven main groups that were subdivided into 20 subgroups. Seven subgroups contained no type or collection strain. Among the human strains, the type strains of Bifidobacterium pseudocatenulatum and B. catenulatum fell into group I, which contained the type strains of B. adolescentis (subgroup Ib), B. dentium (subgroup Ic), and B. angulatum (ungrouped). The type strain of B. breve belonged to subgroup IIIa1, and the type strains of B. infantis and B. longum fell into subgroup IIIb1. Group VII comprised only wild strains that were isolated from human infant feces. Among the animal strains, group II consisted mainly of bifidobacteria that were isolated from pig feces and contained the type strains of B. suis (subgroup IIb), B. thermophilum (subgroup IIf), B. choerinum, and B. boum (ungrouped). Wild strains belonging to group V were isolated from pig, calf, cow, and chicken feces; this included the type strains of B. animalis (subgroup Va), B. magnum (subgroup Vb), B. pseudolongum, and B. globosum (subgroup Vc). The strains of human origin (groups I, III, and VII) were well separated from the animal strains (groups II, IV, and V). It was not surprising that the wild strains isolated from surface water or sewage were distributed in the animal groups as well as the human groups. Thus, bifidobacteria can be considered to be successful indicators of human or animal fecal pollution when they are correctly classified. The acidification patterns were not adequate to differentiate Bifidobacterium species, as determined previously by Mitsuoka (Bifidobacteria Microflora 3:11-28, 1984) and Scardovi (p. 1418-1434, in P. H. A. Sneath, N. S. Mair, M. E. Sharpe, and J. G. Holt, ed., Bergey's Manual of Systematic Bacteriology, vol. 2, 1986). However, enzymatic tests furnished new taxonomic criteria for the genus. PMID- 1742201 TI - Codes and abbreviations for approved of effectively published names of genera of bacteria published from January 1980 to December 1990. AB - Lists of abbreviations for genus names of bacteria are expanded to accommodate 103 new entries which are names that have been validity published since the publication of an updated list by Rogosa et al. in 1986 (Int. J. Syst. Bacteriol. 36:464-472). These abbreviations are provided to serve the need for appropriate codified abbreviations for use in processing or indexing of information on computers. PMID- 1742202 TI - Validation of the publication of new names and new combinations previously effectively published outside the IJSB. List no. 39. PMID- 1742203 TI - On the Helicobacter species isolated from the pig-tailed macaque. PMID- 1742204 TI - Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz. AB - Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it. PMID- 1742205 TI - Effects of ketamine, thiopental sodium and propofol on muscle contractures in rat diaphragm in vitro. AB - The effects of commonly used intravenous anaesthetic agents ketamine, thiopental sodium and propofol on the caffeine-alone or halothane-plus-caffeine-induced muscle contractures were investigated to determine safety for use in patients susceptible to malignant hyperthermia (MH). The muscle strips from rat diaphragm were exposed to one of these anaesthetic agents prior to challenge with caffeine 8 mmol/l alone or halothane 3% plus caffeine 8 mmol/l together. None of the three agents induced contractures when added alone. Ketamine 100 mumol/l and thiopental sodium 300 mumol/l augmented neither caffeine-alone nor caffeine-with-halothane contractures significantly and these two agents appear to be safe for use in MH susceptible patients. In contrast, propofol 150 mumol/l augmented these contractile responses significantly and may not be recommended for use in patients known to be susceptible to this anaesthetic complication. PMID- 1742206 TI - Combined coumarin and omental transfer treatments for canine proximal obstructive lymphoedema. AB - In a canine model both coumarin treatment (believed to act by increased local proteolysis) and surgical transfer of a bridge of vascularized, lymphatic-rich omentum cause significant reduction of experimental lymphoedema. The present paper describes the effects of consecutive application of these two types of treatment. Ten dogs were divided into two equal groups: Group 1 Coumarin treatment, 6 months; no treatment, 6 months; omental transfer, 6 months; or Group 2 Omental transfer, 12 months (biopsied at 6 months); coumarin treatment, 6 months. Prior to treatment the excess limb circumferences were 2.66 and 3.01 cm in Groups 1 and 2 respectively. In Group 1, 6 months coumarin treatment alone reduced swelling by 0.78 cm and the final reduction in swelling at 18 months was 1.03 cm. In Group 2, reduction in swelling 6 months after omental transfer alone was 0.96 cm and the final reduction at 18 months was 2.05 cm. The findings indicate that in Group 1 there is an additive effect of the two types of treatment. However, in Group 2 it is not possible to be certain whether the improvement that occurred between 6 and 18 months also reflects an additive effect or a later consequence of the earlier omental transfer. PMID- 1742207 TI - Morphological and morphometric studies of the airways of sheep with acute airway hypersensitivity to inhaled Ascaris suum. AB - The airways of 12 sheep with naturally-occurring allergic airway hypersensitivity, six of which had changes in both airway resistance and dynamic lung compliance (Group A) and six of which had changes in only dynamic lung compliance (Group B), were compared quantitatively with six non-reacting sheep (Group C) in order to examine the relation between airway hypersensitivity and various morphological features thought to be related to airway hypersensitivity. Compared to the non-reacting sheep (Group C), the hypersensitive sheep (Groups A and B) had a thinner epithelium in medium bronchi and bronchioles, fewer goblet cells in bronchioles, and greater gland area at most airway levels. The differences of the gland dimensions and the types of mucosubstance between hypersensitive and non-reacting animals were more variable. No significant differences between the three groups were noted with regard to luminal occlusion or epithelial sloughing and squamous metaplasia. Although there was a positive association between epithelial thickness and goblet cell density in the small airways, the development of allergic airway hypersensitivity in sheep may occur in the absence of major morphological changes in the airway epithelium. PMID- 1742208 TI - Contribution to the study of septal fibrosis of the liver. AB - Cellular and vascular proliferation in the perisinusoidal area of the acinar zone III of the liver preceded the formation of septal fibrosis in rats repeatedly treated with intraperitoneal injections of pig serum. Deposition of type I, III, IV and V collagens and increased amounts of fibronectin and laminin were also observed. Immunochemical staining for actin, elastin and desmin better disclosed the rich vascularization of the fibrous septa. Hypertrophy and hyperplasia of sinusoidal fat-storing cells point to the main role of such cells in the process of septum formation, but other connective tissue cells, such as mast-cells, were also present. These changes seemed to result from stimulation of the sinusoidal macrophage/fat-storing-cell system by foreign material present in the pig serum. The model may be useful for further studies on pathogenesis of septal fibrosis of the liver. PMID- 1742209 TI - A fall in duodenal PGE2 synthesis precedes histological changes and ulceration in the cysteamine model of duodenal ulceration. AB - The temporal association of histological damage and mucosal prostaglandin E2 (PGE2) synthesis was examined in the cysteamine model of duodenal ulceration in the rat. Four groups of 10 animals were used; a control group (which had a light ether anaesthetic, an i.m. injection of vehicle and were killed 18 h later) and three treatment groups (which were similarly treated but injected with cysteamine (0.3 mg/g body weight) and killed at 6, 18 or 24 h). Estimates of duodenal PGE2 synthesis and histological assessment of mucosal damage were performed. There were four early deaths in the 24-h group due to intra-thoracic haemorrhage. The 6 h group appeared normal macroscopically. There were seven established and three early ulcers in the 18-h group and two established and four early ulcers in the survivors of the 24-h group. Microscopically, the 6-h group did not differ from controls, but the 18 and 24-h groups showed evidence of mucosal damage compared to the control group (P less than 0.001). All three treatment groups synthesized less PGE2 than did the control group (P less than 0.001). Thus at 6-h post injection, a decrease in PGE2 synthesis was evident but mucosal damage occurred later. Histological features correlated negatively with PGE2 synthesis (P less than 0.001). PMID- 1742210 TI - Effects of dietary fatty acids on the early stages of neoplastic induction in the rat pancreas. Changes in fatty acid composition and development of atypical acinar cell nodules. AB - Diets enriched with fat, especially unsaturated fat, promote experimental pancreatic carcinogenesis, but little is known of the effects of individual fatty acids. The effect of stearic and oleic acid on pancreatic fatty acids and atypical acinar cell nodules (preneoplastic lesions) was studied in 14-day-old weanling male Leeds strain rats (n = 60) given the carcinogen azaserine. Rats were allocated to one of six groups: untreated controls (n = 10), 20% stearic acid diet (n = 10), 20% oleic acid diet (n = 10), carcinogen alone (n = 10), carcinogen plus 20% stearic acid diet (n = 10) or carcinogen plus 20% oleic acid diet (n = 10). Azaserine was administered by intraperitoneal injection in a dose of 30 mg/kg at 2, 3 and 4 weeks of age. When total lipid extracts of pancreas were examined, there was an increase in stearic acid in the stearic acid fed group and an increase in oleic acid in the oleic acid fed group, irrespective of carcinogen treatment. The relative content of all other pancreatic fatty acids was suppressed by feeding oleic acid. At 26 weeks, the number and volumetric indices of pancreatic atypical acinar cell nodules was increased only in rats given azaserine and oleic acid. The enhancing effect of oleic acid on pancreatic carcinogenesis may be associated with pancreatic fatty acid changes. PMID- 1742211 TI - Hydronephrosis: prevention by restoration of urinary concentrating ability using desamino-8D-arginine vasopressin (DDAVP) in Brattleboro rats. AB - Male Brattleboro rats with hereditary diabetes insipidus (BDI) were lifetime treated with the vasopressin V2 receptor agonist desamino-8D-arginine vasopressin (DDAVP), given daily in the drinking fluid. The DDAVP-treated adult male BDI rats drank 34 +/- 6 ml/24 h (mean +/- s.e.m.) and excreted urine volumes of 22 +/- 5 ml/24 h compared with their age-matched untreated controls of 142 +/- 12 and 115 +/- 7 ml/24 h respectively. There was no significant difference between the mean body weights of chronically DDAVP-treated BDI rats (198 +/- 9 g) and untreated animals (207 +/- 9 g). Morphometry of sections of kidney confirmed extensive hydronephrosis in the right kidneys of the control untreated Brattleboro rats only. This was quantified as the area of pelvis expressed as a percentage of total cross-sectional area of kidney (17 +/- 3 compared with 5 +/- 1% in the chronically DDAVP-treated rats; P less than 0.002). Medium-term treatment of adult BDI rats with DDAVP reduced daily fluid output towards normal rat values but hydronephrosis was still present. These observations indicate that the restoration of fluid balance in adult BDI rats by treatment from conception with DDAVP may be an important factor in preventing the development of hydronephrosis in these animals. PMID- 1742212 TI - In-vitro interaction of human macrophages with Pneumocystis carinii. AB - Pneumocystis carinii is an important opportunistic pathogen in patients with compromised cell-mediated immunity. T-cell and macrophage function are believed to be of prime importance in defence against this organism. The present ultrastructural study is aimed at the analysis of the interaction between human macrophages and P. carinii in vitro. Adherent peripheral blood mononuclear cells from healthy volunteers were exposed in vitro to Pneumocystis derived from lungs of steroid-treated rats. The macrophages were harvested at different intervals and studied by transmission and scanning electron microscopy. The material used for inoculation of macrophages was of identical morphology to previously described P. carinii. When mixed with Pneumocystis in vitro, the macrophages appeared to move towards the organism, extended pseudopods and ingested trophozoites and cysts. Within 24 h, intracellular Pneumocystis underwent progressive degeneration inside macrophage vacuoles. This study highlights the possible role of macrophages in host defence against P. carinii. PMID- 1742213 TI - The role of surfactant in the pulmonary reaction to mineral particles. PMID- 1742214 TI - Early bone marrow transplantation for patients with potentially curable malignancies. PMID- 1742215 TI - How should prognostic factors influence therapy in follicular lymphomas? PMID- 1742216 TI - Clinical research in advanced breast cancer: back to the future? PMID- 1742217 TI - How should we treat disseminated seminoma? PMID- 1742218 TI - Multiple confirmatory trials. How can additional studies be of value? PMID- 1742219 TI - Cancer diagnosis by molecular genetic probes: the present and the promise. PMID- 1742220 TI - Adjuvant therapy of colon cancer: lessons while looking for breakthroughs. PMID- 1742221 TI - The identification of discrete prognostic groups in low grade non-Hodgkin's lymphoma. The Scotland and Newcastle Lymphoma Group Therapy Working Party. AB - A prognostic model was developed by examination of the prospectively recorded presentation characteristics of patients presenting with low grade non-Hodgkin's lymphomas (LGL). A geographically distinct group (Edinburgh and Borders) was excluded in order to test the validity of the model based on the rest of the Scotland and Newcastle Lymphoma Group (SNLG) population. Between 1979 and 1987 506 patients presented with low grade lymphoma according to Working Formulation definition within one of each of the three main pathology categories. The median available follow-up was 47 months. In a multivariate analysis performance status, age, stage, gender and haemoglobin all contributed separately. 25% of all patients had relatively good prognosis with a median survival not reached and 84% alive at 5 years. Conversely for the worst prognostic group of 25% of patients the median survival is 18 months with only 26% surviving at 5 years. Finally for the intermediate group of 50% of all patients, median survival is 69 months with 58% alive at 5 years. These striking prognostic separations are shown also to be valid in sub-group analysis. Thus young patients within any pathology subgroup have been identified with bad prognostic lymphoma for whom novel strategies in therapy should be devised. PMID- 1742222 TI - Epirubicin in breast cancer patients with liver metastases and abnormal liver biochemistry: initial weekly treatment followed by rescheduling and intensification. AB - Fifty-two consecutive patients with breast cancer and liver metastases have been treated with epirubicin. All had a serum aspartate aminotransferase more than twice the upper limit of normal or a raised bilirubin. Initial treatment was with 6 cycles of weekly epirubicin 25 mg/m2. In patients whose liver biochemistry improved sufficiently, treatment was then changed to a 3-weekly schedule and an attempt was made to increase dose-time intensity during a further 6 cycles of epirubicin. The UICC response rate was 15/52 (29%, with 95% confidence intervals 18-42%) and median response duration was 34 weeks. All 23 patients who were eligible for rescheduling received epirubicin 3-weekly, but escalation of dose intensity was possible in only 5 patients. The activity and tolerability of weekly epirubicin has been confirmed in patients with liver metastases from breast cancer. However, late dose escalation was impracticable in the majority of patients and did not appear to improve outcome. PMID- 1742223 TI - Folinic acid + 5-fluorouracil (5-FU) versus equidose 5-FU in advanced colorectal cancer. Phase III study of 'GISCAD' (Italian Group for the Study of Digestive Tract Cancer). AB - In a multicentre Phase III trial, 182 patients were randomized to either folinic acid (FA) (200 mg/sqm i.v. x 5 days) + 5-fluorouracil (5-FU) (400 mg/sqm i.v. in 15' x 5 days) every 4 weeks (Arm A), or to 5-FU alone at the same dosage (Arm B). Response rates were 20.6% (Arm A) and 10% (Arm B) with a significant (p = 0.046) advantage for FA + 5-FU. Median time to progression (6 and 6 months) and overall survival (11.5 and 11 months) were similar in the 2 groups of patients, while neither treatment was effective in reducing pain or improving performance status. Univariate analysis showed that no prognostic factors other than treatment influenced response, although survival was affected by the number and site of metastases, performance status, and the presence and degree of pain. Toxicity was acceptable and lower in comparison with other Phase II-III trials, with no significant difference between the 2 arms. However, in individual patients, grade 3-4 side effects (mainly stomatitis and diarrhoea) were observed, particularly in patients receiving FA: this led to interruption of the treatment in 7 cases. The superiority, in terms of objective response, of FA + 5-FU over 5-FU alone would seem to justify a large-scale evaluation of this combination in the adjuvant setting. Further improvements in relation to advanced disease (i.e., modifications to the schedule and/or introduction of other modulators) are warranted. PMID- 1742224 TI - A randomized, double-blinded study comparing six doses of batanopride (BMY-25801) with methylprednisolone in patients receiving moderately emetogenic chemotherapy. AB - Several agents in a new class of antiemetic compounds, 5-hydroxytryptamine (5 HT3) antagonists, have shown promise as effective antiemetics with fewer side effects than metoclopramide. One of these agents, batanopride, produced no severe toxicity at doses that prevented emesis due to chemotherapy in early Phase I trials. We conducted a randomized, double-blinded, 7 arm clinical trial to: (1) identify the presence of a dose-response for complete protection from emesis, and (2) compare batanopride with a standard antiemetic, methylprednisolone if a dose response was found not to exist. Prior to chemotherapy, six patient groups each received a single intravenous dose of batanopride ranging from 0.2 to 6.0 mg/kg whereas a seventh group received methylprednisolone 250 mg intravenously. Chemotherapy-naive cancer patients scheduled to receive moderately emetogenic chemotherapy were eligible. Primary treatment outcomes that were recorded and analyzed included the number of episodes of emesis, the time to the first episode of emesis as well as the frequency and severity of nausea. Two hundred and eight patients accrued between April 1989 and February 1990 were evaluable for response. A significant dose-response effect for complete protection from emesis was not seen over the first 24 hours after chemotherapy (p = 0.102). However, a linear dose-response effect for time to first emesis was evident in a multivariate analysis (p = 0.029). While the highest batanopride dose group was associated with a higher complete protection rate (CPR) than the control group, this group also exhibited a higher incidence of diarrhea (p = 0.013), hypotension, and electrocardiographic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742225 TI - Cisplatin and etoposide in advanced colorectal carcinoma. AB - The cisplatin (P) and etoposide (E) combination has been found to be active in several types of solid tumors. It has never been previously tested in advanced colorectal cancer. Thirty-three patients with advanced colorectal cancer were treated with this combination. Five patients responded (1 complete and 4 partial responses) with an overall response rate of 15% (95% confidence limits, 3%-27%). Responses were seen in both untreated (3/16) and pretreated (2/17) patients. The median duration of response was 28 weeks (range: 23; 80), the median time to progression was 16 weeks (range 2; 80) and the median survival time for all entered patients was 38 weeks (range: 2; 187+). These results suggest that the PE combination has a low but definite activity in advanced colorectal carcinoma, particularly in previously untreated patients. PMID- 1742226 TI - Continuous infusion of 5-fluorouracil in ovarian cancer patients refractory to cisplatin and carboplatin. PMID- 1742227 TI - Mouth cooling to prevent doxorubicin-induced stomatitis. PMID- 1742228 TI - UKCCCR randomized study of chemo-radiotherapy for advanced head and neck carcinoma. PMID- 1742229 TI - Use of an electron beam for post-mastectomy radiotherapy: 5-year follow-up of 500 cases. AB - Since 1982, the standard method of postmastectomy regional radiotherapy at the Christie Hospital has been to use a single electron field of fixed energy (8 MeV) to irradiate the chest wall, matched to a single megavoltage field (4 or 8 MV) irradiating the nodal areas in the axilla and supraclavicular fossa. (A separate parasternal field was not used.) All 500 cases treated in 1982 and 1983 with this method were reviewed (median follow-up 59 months). Four hundred and twenty-two were referred directly post-mastectomy and 78 for local recurrence after previous mastectomy. Of these, 42 were treated palliatively, and 458 with radical intent. In radical cases the given dose in both fields was 40 Gy in 15 fractions in 3 weeks. The overall survival (n = 458) was 51% (actuarial) at 5 years. At 5 years the local recurrence rate by site and UICC stage were as follows: chest wall - all Stages 17%, Stage I 4%, Stage II 13%, Stage III 26%, recurrent cases 21%; axillary recurrence - all Stages 20%, Stage I 4%, Stage II 10%, Stage III 22%, recurrent cases 39%; supraclavicular recurrences - all Stages 9%. Only one patient of the 500 treated had a parasternal recurrence. Late effects included mild telangiectasia in the electron field and asymptomatic apical lung fibrosis in the photon field. There was no match line fibrosis. PMID- 1742230 TI - A phase II study of 5-fluorouracil, adriamycin and mitomycin-C in adenocarcinoma of the oesophagus. AB - We have evaluated the effect of 5-fluorouracil 600 mg/m2, doxorubicin ('Adriamycin') 40 mg/m2, and Mitomycin-C 4 mg/m2 (FAM) in two groups of patients with adenocarcinoma of the oesophagus, as either a preoperative or primary treatment. Response was assessed by barium swallow, CT scan, and measurement of metastases where present. Toxicity was as reported for FAM in gastric cancer. In the operated group 8 of 22 patients (36%) showed a partial response following two courses of FAM. Resection was completed in 20 patients, with six hospital deaths (30%). Of the 14 patients who were discharged from hospital, 8 have died (median 8 months) and 6 are alive at 12 to 27 months, with known recurrence in 1. In the non-operated group 6 of 17 patients (35%) showed a response, one complete, following one to six (mean 4.2) courses of FAM. Fifteen patients have died (median 5 months), and 2 are alive and free from disease at 12 and 17 months. Neoadjuvant therapy with FAM in adenocarcinoma of the oesophagus offers no advantage over surgery alone, although with inoperable disease FAM may be of use in palliation. PMID- 1742231 TI - Descriptive epidemiology of primary central nervous system tumours in children: a population-based study. AB - This study was undertaken to investigate the incidence, outcome and referral patterns of central nervous system tumours in a defined childhood population over a recent 5-year period. The study incorporated pathological review of all available diagnostic material and follow-up assessed survival at a minimum of 5 years from diagnosis. One hundred and forty-seven cases were reviewed, representing an annual incidence of 26.5 per million children aged less than 15 years. The distribution of individual diagnoses by age, sex and anatomical site was similar to comparable data collected previously in the United Kingdom and North America, but the inclusion of 28 cases (19%) without biopsy suggested that the wider use of computed tomography might account for a small increase in incidence over previous estimates. Analysis of referral to the Regional Paediatric Oncology Unit showed that the patients referred were younger than those not referred and were over-represented amongst the diagnoses of medulloblastoma, ependymoma and brain stem glioma, which carry the worst prognosis. Survival for all diagnoses together was 51% at 5 years, ranging from 13% for unbiopsied brain stem gliomas to 100% for juvenile astrocytomas. Referral to the Regional Unit appeared to have some survival advantage for children with medulloblastoma, although this was not statistically significant. Accurately reviewed data such as these are essential in order to assess current workload and treatment success, in addition to enabling investigation of future diagnostic and treatment strategies. PMID- 1742232 TI - The influence of some factors on local control of early glottic cancer. AB - A total of 135 patients with T1N0M0 and T2N0M0 carcinoma of the vocal cord were treated during a 20-year period at St Mary's Hospital in Portsmouth by local radiotherapy. A total of 122 patients were available for local control analysis. The local control of T1 tumours was 80.5%, and for T2, 51.1%, total T1 + T2 local control was 69.7% (P less than 0.001). The only other factor in univariate analysis, which influenced the results was the overall treatment time. In the group of patients treated by an overall time of 45 days or less, the local control was 83.7%. For longer time it was 62% (P less than 0.02). Multivariate analysis confirmed these findings but brought out the importance of vocal cord mobility as the best discriminating factor between local control and failure, followed by overall treatment time. PMID- 1742233 TI - Chemotherapy versus radiotherapy for stage I-II intermediate grade non-Hodgkin's lymphomas. AB - The clinical outcome of 149 patients with Stage I-II intermediate grade non Hodgkin's lymphomas was analysed. There were 77 (52%) males and 72 (48%) females. Their median age was 58 years. Eighty patients (54%) had Stage I disease and 69 (46%) Stage II. Twenty-nine (20%) of them received radiotherapy only, 75 (50%) doxorubicin-containing chemotherapeutic regimens and 45 (30%) other less intensive chemotherapy. Sixty-two patients had additional radiotherapy following chemotherapy. Patients receiving other less intensive chemotherapy were significantly older (P = 0.0001) and those receiving radiotherapy alone had a significantly higher proportion of Stage I disease (P = 0.007). Patients receiving less intensive chemotherapy had a significantly low complete response (CR) rate. Patients receiving radiotherapy alone had a significantly high relapse rate and low disease-free survival following CR. However, there was no significant difference in overall survival regardless of the mode of therapy. This lack of survival advantage might be related to the effective salvage chemotherapy in some of the radiotherapy failures and the occasional chemotherapy related mortality. Additional radiotherapy following chemotherapy did not appear to give further benefit. PMID- 1742234 TI - Abdominopelvic radiotherapy following surgery and chemotherapy in advanced ovarian cancer. AB - Thirty advanced ovarian cancer patients have been treated with sequential multimodality treatment including primary surgery, cisplatin or carboplatin-based polichemotherapy, second-look laparotomy followed by abdominopelvic irradiation (moving strip or open-field technique). Toxicity related to the combined treatment was acceptable: only three patients failed to complete and two patients delayed the prescribed course of radiotherapy because of acute myelosuppression or gastroenteric disturbances. One patient without evidence of disease required laparotomy for bowel obstruction one month after completion of radiotherapy. No other chronic toxicity of clinical significance has been observed. Actuarial three-year survival significantly correlated with residual disease at the start of radiotherapy: no residuum, 100%, microscopic disease, 52%; less than 2 cm macroscopic disease, 27.4% (P less than 0.05), whereas recurrences were less frequent only in the group of pathological complete responders (3/9) compared to patients with limited disease (6/11 with micro and 7/10 with macroscopic residuum). In conclusion radiotherapy following surgery and chemotherapy is not associated to serious morbidity but its value in improving progression-free survival rates has to be tested in randomized trials. PMID- 1742235 TI - Lung abscess: a fatal complication of treatment for testicular teratoma. AB - We describe a patient with widely metastatic testicular teratoma who responded to intensive combination chemotherapy but developed a lung abscess in a necrotic tumour cavity, leading to death before surgical resection of residual lesions could take place. Post-mortem examination revealed necrotic tissue and mature differentiated teratoma, with no evidence of frank malignancy. This complication has not been previously reported in treated teratoma. Resolution of an abscess developing in a pre-existing thick-walled lesion is less likely with antibiotics alone. Awareness of this might salvage potentially curable cases by earlier surgical intervention. PMID- 1742236 TI - Selective embolization of internal iliac artery for massive haemorrhage from bladder secondary to carcinoma. AB - Uncontrolled haemorrhage from the urinary bladder secondary to carcinoma can at times be a life-threatening complication. We report a case of recurrent carcinoma of bladder where all the conservative measures for controlling hematuria had failed. Selective embolization of both internal iliac arteries was undertaken which controlled haematuria within 12 hours of the procedure. The procedure had not caused any complication up until the patient was last seen 5 months after the procedure. PMID- 1742237 TI - Radical external beam radiotherapy for localized carcinoma of the prostate using a hypofractionation technique. PMID- 1742238 TI - Victim blame and the disinhibition of sexual arousal to rape vignettes. AB - The present study examined the effects of differing levels of victim blame on the sexual arousal of males to rape vignettes. In the first experiment, a between subjects experimental design was used to compare four groups of eight university males for their erectile responses to vignettes rated as low, medium, and high along a victim blame continuum. All groups found a consenting vignette more arousing than a nonconsenting vignette, however, this difference was significantly smaller for subjects in the high blame condition compared to the low and medium blame conditions. A second experiment supported the disinhibiting effect of the high victim blame manipulation using 12 university males in a within-subjects experimental design. The disinhibiting influence of victim blame on male sexual arousal to rape cues was discussed in relation to our broader understanding of sexual assault. PMID- 1742239 TI - Lesbians in currently aggressive relationships: how frequently do they report aggressive past relationships? AB - Findings are reported from a survey examining the frequency with which women in currently aggressive same-sex relationships also report aggressive past relationships involving female partners, male partners, or members of their family of origin. Particular attention is paid to victims who also used aggression and their perceptions of whether their aggressive behavior was self defensive or mutually aggressive. Results indicate that about one-fourth of participants had been victims of aggression in current relationships, roughly two thirds had been victimized by a previous male partner, and almost three-fourths had experienced aggression by a previous female partner. Among those reporting having been both victims and users of aggression, about one-fifth had used aggression in their current relationship, almost one-third used aggression with a previous male partner, and nearly two-thirds had used aggression with a previous female partner. A majority of victims who had also used aggression with a previous male partner characterized this use as self-defense, as compared to only 30% of those who had used aggression with a female partner. Instead, aggression in relationships involving a female partner was most frequently described as mutually aggressive in nature. PMID- 1742240 TI - Battered wives: the home as a total institution. AB - This paper is based on research which examined the lives of Israeli battered women from the phenomenological aspect. Thirty-five unstructured interviews were carried out in a shelter for battered women. The women's accounts suggest that the situation of battered women resembles that of inmates of total institutions, as defined by Goffman (1961). Physical barriers are imposed upon them, and they go through a process of mortification of the self which begins soon after the marriage. Compulsory confinement to the house damages the self and diminishes the ability to cope. Furthermore, it cuts the women off from external sources of physical help and moral support. Increased understanding of this harsh reality would benefit the social agencies engaged in helping battered women. PMID- 1742241 TI - Over- vs. undercontrolled hostility: application of the construct to the classification of maritally violent men. AB - The purpose of the present investigation was to evaluate the applicability of Megargee's (1967) distinction between over- and undercontrolled hostility to maritally aggressive men. Subjects were 41 men who were referred for treatment for physical marital violence. Data were derived from a written battery of self report measures. Overcontrolled hostile men showed patterns of abuse in which violent episodes were more severe but less frequent and in which the wife was the sole target of the aggressive behavior. Undercontrolled hostile husbands were more generally aggressive and more frequently aggressive. Additionally, undercontrolled husbands were more likely than overcontrolled husbands to have witnessed violence in their families of origin and to have had rejecting mothers. Implications for the assessment and treatment of marital violence are discussed. PMID- 1742242 TI - Female victims of homicide: a portrait of their killers and the circumstances of their deaths. AB - The population of 131 arrestees for homicides committed against females during 1982 and 1983 in Detroit, Michigan, is analyzed in the context of their killings. Analyses include demographic and social characteristics of offenders and victims, demographic and social relationships between offenders and victims, circumstances of offense, and arrest disposition. Where feasible, comparisons are made with general populations and samples of homicide offenders. PMID- 1742243 TI - The relationship between skin maturation and electrical skin impedance. AB - When performing electrophysiological testing, high electrical impedance values are sometimes found in neonates. Since excessive impedance can invalidate test results, a study was conducted to delineate the relationship between skin maturation and electrical skin impedance. This study investigated the skin impedance in 72 infants ranging from 196 to 640 days of age from conception. Regression analyses demonstrated a significant relationship between impedance and age, with the highest impedance centered around full-term gestation with values falling precipitously at time points on either side. Clinically, impedance values fall to normal levels at approximately four months following full-term gestation. Skin impedance values are low in premature infants, but rapidly increase as the age approaches that of full-term neonates. Low impedance values in premature infants are attributed to greater skin hydration which results from immature skin conditions such as 1) thinner epidermal layers particularly at the transitional and cornified layers; 2) more blood flow to the skin; and 3) higher percentage of water composition. These factors facilitate the diffusion of water vapor through the skin. As the physical barrier to skin water loss matures with gestational age, the skin impedance reaches a maximum value at full term neonatal age. After this peak, a statistically significant inverse relationship exists between electrical skin impedance and age in the first year of life. This drop in skin impedance is attributed to an increase in skin hydration as a result of the greater functional maturity of eccrine sweat glands. PMID- 1742244 TI - Cutaneous responses to topical methyl nicotinate in human forearm and vulvar skin. AB - In order to identify and define differences in percutaneous absorption and microcirculatory sensitivity between forearm and vulvar skin we studied the response of human forearm and vulvar (labium majus) skin to topical methyl nicotinate (MN) in 11 healthy premenopausal volunteers. MN-induced erythema was assessed by laser Doppler velocimetry (LDV). The following parameters were compared: 1) basal cutaneous blood flow, 2) the time to peak response, 3) the magnitude of LDV peak response, 4) the area under the LDV response-time curve and 5) the decay time to 75% of peak response. Basal cutaneous blood flow at the vulva was higher than at the forearm (P less than 0.05); the magnitude of peak response was lower at the vulva than at the forearm (P less than 0.01); the area under the curve was lower at the vulva than at the forearm (P less than 0.001); the decay time to 75% of peak response was shorter at the vulva than at the forearm (P less than 0.001). The time to peak response showed no significant differences between sites. The results indicate that the MN-induced vasodilatation is less intense and lasts shorter in vulvar compared to forearm skin. PMID- 1742245 TI - Changes in cutaneous microcirculation, hemorrheology and platelet aggregation function in dermatomyositis. AB - Marked disturbance of microcirculation was observed in 85 cases of dermatomyositis: decrease in number and irregular pattern of the capillaries, many being tortuous and dilated and having a slow and granular blood stream, as well as an increase of vascular permeability. The changes were more marked in cases with visceral disorders, or in active disease; however, there was no correlation between these changes and the duration of illness. Blood hyperviscosity was found in an hemorrheological study. The cause is considered to be due to high plasma viscosity, high fibrinogen levels, and increase of aggregation of erythrocytes and platelets. Modulation of microcirculation is advisable in the treatment of dermatomyositis. PMID- 1742246 TI - The effect of 1,25-dihydroxyvitamin D3 on the growth and differentiation of cultured human outer root sheath cells from normal subjects and patients with vitamin D-dependent rickets type II with alopecia. AB - We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth and differentiation of cultured human hair outer root sheath cells (ORSC) from normal subjects and patients with vitamin D-dependent rickets type II (DDR-II) with alopecia. 1,25(OH)2D3 dose-dependently suppressed the plating efficiency, clonal growth, and DNA synthesis of normal ORSC. It enhanced the cornified envelope formation and caused morphological changes in the cells. All results indicated the existence of specific receptors for 1,25(OH)2D3 in the ORSC, and suggest that 1,25(OH)2D3 is a potent inhibitor of proliferation of ORSC as well as a stimulator of terminal differentiation. However, the cells from DDR-II patients with alopecia did not respond to 1,25(OH)2D3, suggesting a lack of the specific receptors in the cells. The differences in the cellular response to the hormone between the normal ORSC and those from the patients were apparent and easily distinguishable, therefore this experiment may be a rapid and simple diagnostic test for DDR-II patients with alopecia. Large number of hairs were difficult to obtain from patients with alopecia, and we developed a new culture method to accomplish these studies from a few plucked hair follicles. Our system may be useful in the culture of ORSC from limited number of follicles, and could be utilized to analyse the cellular characteristics of ORSC in patients with hair diseases. PMID- 1742247 TI - A three-year photopatch study in Thailand. AB - Photopatch testing was performed on 274 patients who had history of photosensitivity at the Institute of Dermatology Thailand from 1987 through 1989. A total of 92 positive photocontact reactions and 71 positive contact reactions were seen. The most frequent positive photopatch test reactions were to sulfanilamide (18.2%) followed by Jadit (4.4%) chlorpromazine (3.6%) promethazine (3.6%) and fenticlor (3.2%). The most common photodermatoses was polymorphous light eruption (60.9%). Photocontact dermatitis was established in 28 patients (10.2%) while other skin diseases aggravated by sunlight were seen in 47 patients (17.2%). PMID- 1742248 TI - Processing and statistical analysis of laser Doppler data applied to the assessment of systemic anti-inflammatory drugs. AB - Continuous laser Doppler measurements of methyl nicotinate-induced skin inflammation have been used to evaluate the activities of three oral non steroidal anti-inflammatory drugs, indomethacin 50 mg (Indocid), tiaprofenic acid 100 mg (Surgam) and sodium acetylsalicylate 1 g (Catalgine). They were compared in a single-blind, randomized, intra-individual comparison (N = 16) versus placebo (lactose). One hour after each drug was ingested, four concentrations of methyl nicotinate were applied to the subject's forearms. Simultaneous skin blood flow (SBF) measurements were then carried out on the four tested zones, by use of four calibrated laser Doppler flowmeters. Computerized processing of recorded SBF levels provided data related to flow amplitude, kinetics and magnitude (area under the curve) of the reactions. A detailed statistical analysis was performed to establish the selectivity of this type of test and the following points were demonstrated: adjustment of SBF data to baseline did not improve precision, data had to be log-transformed before analysis, and magnitude data gave the best product discrimination. Under the conditions of this study, i.e. one hour after oral administration and for the indicated doses, the tested products could be classified, in terms of anti-inflammatory activity, as follows: Lactose less than Indomethacin 50 mg = Tiaprofenic acid 100 mg less than Sodium acetylsalicylate 1 g. PMID- 1742249 TI - Intraepidermal distribution of free amino acids in porcine skin. AB - The study describes the vertical distribution of free amino acids in the porcine epidermis as compared to the human integument, using a micro-determination TLC method based on the reaction of amino acids with dansyl chloride. This microanalytical approach demonstrated 22 free amino acids, with the relatively largest amounts being present for acidic amino acids and their amides. It was obvious that the relative amounts of certain amino acids (alanine, proline, valine, glutamine, histidine, glycine, threonine) decreased, whereas acidic amino acids (glutamic acid, aspartic acid) increased from the stratum basale up to the stratum corneum. This distributional pattern could be verified for the dorsal and lateral body regions of the pig breeds used, and for man. The results obtained are discussed in view of the development of epidermal keratinization. PMID- 1742250 TI - Computed tomographic analysis of gallbladder stones: correlation with chemical composition and in vitro shock-wave lithotripsy. AB - The recent advent of nonsurgical treatment for gallstones requires accurate in vivo analysis of their chemical composition in order to select the best candidates. As a preliminary work, we undertook an in vitro CT examination of 53 surgically removed gallstones and compared their CT patterns with their chemical composition. Those results were correlated with in vitro lithotripsy of the gallstones. The CT appearances were classified as follows: laminated (43%), dense (32%), rimmed (11%), isodense (8%) and faint (6%). The dense pattern contained a high calcium content. As the CT density increased, the calcium content increased, but the cholesterol content decreased proportionally. The number of shock waves needed to break down a gallstone less than 2 mm in size increased with stone volume and the cholesterol content increased but did not have any correlation with the calcium content level. As a result we found the CT examination to be a very sensitive method in detecting small amounts of calcium content in gallstones and the CT pattern and density of the gallstones were well correlated with their chemical composition, therefore in vivo CT examinations for ESWL candidates are desirable. PMID- 1742251 TI - Correlation of esophageal lengths with measurable external parameters. AB - Previous data for esophageal lengths are based on age related groups or cadaveric examination, both of which are improper for application to various individualized procedures. Because of the variability in height for any given age and longer length in vivo, individualized approximation is needed. Thus, we measured various anatomical levels of the esophagus using a flexible endoscope and correlated these data with measurable external body intervals. The mean esophageal length was 40.92 +/- 2.79, which is longer than the length derived from cadaveric examinations. Also, esophageal lengths which correlated better with height than any other body intervals, could be calculated from the following equation. Esophageal length from the upper incisors to the esophagogastric junction (L) can be expressed: L = 0.242 x height (Ht) + 2.078 cm (P = 0.000, R2 = 0525). The data from our study indicate that esophageal length can be reliably predicted using external body parameters before employing various procedures. PMID- 1742252 TI - Circulating HBsAg/IgG complexes in idiopathic chronic glomerulonephritis. AB - We measured HBsAg/IgG complexes (CX) quantitatively by ELISA from HBsAg positive serum of 35 liver disease patients, 15 patients with glomerular diseases (8 membranous glomerulonephritis (MGN) 7 membranoproliferative glomerulonephritis (MPGN), and 50 healthy carriers of HBsAg. HbsAg/IgG CX was detected in 26 out of 35 liver disease patients (74.3%), 5 out of 50 healthy carriers (10%), and one of both 8 MGN patients (12.5%) and 7 MPGN patients (14.3%). HBsAg/IgG CX was big in size and wide spread in the liver disease groups but negligible in the healthy carrier group (41 +/- 2.6 ng/ml, n = 5) and MGN (50 ng/ml, n = 1) and MPGN (42 ng/ml, n = 1) group. In the liver disease group, no one suffered from glomerulopathy even with a wide spectrum of HBsAg/IgG CX. These results suggest that HBsAg/IgG CX in plasma is non causative of MGN and MPGN. PMID- 1742253 TI - Type III hypersensitivity reaction in mushroom growers. AB - Some respiratory symptoms in mushroom growers such as mushroom worker's lung develop by inhalation of certain agents arising from the environment of mushroom cultivation. Recently we observed mushroom workers who had respiratory symptoms which might be type III hypersensitivity reaction to the antigen of Pleurotus floridae. We gave questionnaires to all the mushroom growers at one of the biggest cultivation areas of mushrooms, Pleurotus floridae in Pocheon, Kyunggi Province. Those with respiratory symptoms were subjects for the study. CBC, chest X-ray, pulmonary function test, skin test with Pleurotus floridae extract, and precipitin antibody test to Pleurotus floridae were performed in the study subjects. Out of a total 308 mushroom workers, 23 workers (14 males, 9 females) had respiratory symptoms. Their mean age was 45 years, and their mean duration of engagement was 3.4 years. Their main symptoms were cough (100%), sputum (82.6%), dyspnea (43.5%), and fever with chills (13.0%). Two cases showed increased interstitial lung markings on chest X-ray films. Sixteen cases (73.9%) showed precipitin antibodies against P. floridae extract by counterimmunoelectrophoresis. Antibodies against Micropolyspora faeni and Thermoactinomyces vulgaris were not detected in any subject. PMID- 1742254 TI - A case of post-traumatic coronary occlusion. AB - Several cases of transmural myocardial infarction and ventricular aneurysm caused by a blunt trauma of the chest have been reported. Nevertheless, the cases documented with coronary and ventricular angiography are very few. There has always been a debate over the etiological mechanism of such lesions. Since in some cases there was no evidence of coronary lesions, it was postulated that they were produced by direct myocardial contusion, but in other instances the evidence of coronary occlusion was angiographically and pathologically proved. We experienced a case of acute myocardial infarction with ventricular aneurysm secondary to nonpenetrating chest trauma by an umbrella tip and wish to report this unusual case, along with a review of the literature. PMID- 1742255 TI - A case of pulmonary cysticercosis. AB - Cysticercosis, which has a worldwide distribution is found in man, who is usually infected by eating inadequately cooked pork or other contaminated food. Cysticercosis develops most commonly in the muscles and brain. Pulmonary involvement is very rare and also difficult to recognize because pulmonary lesions caused by the presence of cysticerci are difficult to discern from pulmonary infiltrates, because other parasitic infestations or tuberculosis, as well as metastatic lesions, produce similar chest X-ray findings and similar clinical symptoms. We experienced a case of pulmonary cysticercosis confirmed at Gyeongsang National University Hospital by means of an open lung biopsy and treated successfully with praziquantel (50 mg/kg per day for 15 days). This case seems to indicate that pulmonary cysticercosis should be considered as a diagnostic possibility in patients with nodular infiltrates in the lungs, especially in endemic areas, until such infiltrates are otherwise explained. PMID- 1742256 TI - A case of primary T-cell lymphoma of the duodenum. AB - Primary malignant lymphoma located in the duodenum is a rarity. A case of primary lymphoma of the duodenum in a 27-year-old man, in which the 2 discrete masses of duodenal bulb and the second portion with pancreatic head invasion was found, is reported here. Immunohistochemical evaluation of the present case showed that lymphoma cells expressed the T-cell markers MT1 and UCHL1. Treatment consisted of pancreaticoduodenectomy followed by antineoplastic chemotherapy. PMID- 1742257 TI - Autoradiographic and immunohistochemical study on the proliferative kinetics of intestinal metaplasia. AB - In order to elucidate the proliferative behavior of the intestinal metaplasia around gastric cancer, the authors used both in vitro tritiated thymidine (3H thymidine) autoradiography and in vivo bromodeoxyuridine (BrdUrd) immunohistochemistry for labeling the proliferative cells of the normal pyloric glands and metaplastic gastric glands. The results of the methods were comparable: The labeling pattern and the rate of labeling were very similar. In the normal pyloric mucosa, the labeled cells were confined to the isthmus region, indicating that pyloric glandular cells are normally renewed from the isthmus region. On the other hand, a zone of the labeled cells was found in the lower half of the intestinalized mucosa, indicating that cell proliferation took place deep in the mucosa, just like the case of normal intestinal glands. The labeling indices of the pyloric mucosa were 19.4% by autoradiography and 18.0% by immunohistochemistry, and that of the intestinalized gastric glands were 25.2% by autoradiography and 24.2% by immunohistochemistry. In conclusion, both 3H thymidine autoradiography and BrdUrd immunohistochemistry showed that the proliferative kinetics of the intestinalized gastric glands was similar to that of the normal intestinal glands rather than the pyloric glands, i.e. a lower level of proliferative zone and higher labeling index were present. PMID- 1742258 TI - The characteristics of midfacial fractures and the association with ocular injury: a prospective study. AB - Ocular injuries commonly occur in patients with facial fractures. This prospective study was set up to determine the incidence of ocular injuries, as assessed by an ophthalmologist, in patients who had sustained midfacial fractures. Over a 2-year period, a study of 363 patients who had sustained midfacial trauma sufficient to lead to a facial bone fracture (438 fractures) was undertaken and patients received a comprehensive examination by an ophthalmologist and an orthoptist within 1 week of injury. The characteristics of the eye injuries sustained were related to the aetiology of the fracture, the type of fracture, and the sex and age of each patient. Ninety percent of patients sustained ocular injuries of various severities. Sixty three percent of patients sustained only minor or transient ocular injuries, 16% suffered moderately severe ocular injury and 12% experienced severe eye injuries. Road traffic accident was associated with the highest incidence of severe ocular disorder (9/45 = 20%) whilst assaults had the second highest incidence at 11% (20/181). One third of all patients with comminuted malar fracture suffered a severe ocular disorder (9/27) whilst blow-out fracture came second at 16.7% (6/36). Fifty six patients (15.4%) had a decrease in their visual acuity and 9 patients (2.5%) had significant traumatic optic neuropathy. Decrease in visual acuity was the main clinical finding accompanying the majority of significant eye injuries. When ocular injuries were related to aetiology, it was apparent that road traffic accidents and assaults associated with alcohol abuse showed the highest incidence of major ocular dysfunction. It is suggested that all patients sustaining midfacial fracture associated with a significant decrease in visual acuity either pre- or postoperatively should have an early ophthalmological review. PMID- 1742259 TI - Diplopia following midfacial fractures. AB - Over a period of 2 years, 363 patients who had sustained a total of 438 midfacial fractures due to blunt trauma received a full ophthalmological examination within 1 week of injury. Of these, 72 patients (19.8%) developed diplopia. Diplopia was most common following road traffic accidents (31%) and least common with simple falls (10%). Blow-out fractures of the orbit led to double vision in 58% of cases. Eighty two percent of patients recovered from diplopia within 6 months of injury; only 1 patient required squint surgery for double vision. The principal risk factors for diplopia comprise road traffic accidents, blow-out fractures and comminuted malar fractures. Early surgical reconstruction of midfacial fractures with conservative management of concomitant motility disorders has, in our series, resulted in very few patients having diplopia in the long term. PMID- 1742260 TI - Intermaxillary fixation compared to miniplate osteosynthesis in the management of the fractured mandible: an audit. AB - The hospital records of 30 patients with isolated fractured mandibles treated by intermaxillary fixation (IMF) were compared to 30 patients treated by miniplate osteosynthesis. The treatment variables assessed were the period of hospitalisation, the operating time, the use of intensive care or nurse specialing services, the number of outpatient visits, and the cost of materials. The cost of each facility was calculated from six sources, so that the average cost of each method of treatment could be determined. The results showed that the average cost for managing a fractured mandible with IMF was 1000 pounds if the intensive therapy unit (ITU) was used and 919 pounds if ward specialing services (a single nurse looking after the patient) were used. This compared with an average cost of 794 pounds for miniplate osteosynthesis. The extra cost of the materials if miniplates were used could be discounted by the longer period of hospitalisation, the use of ITU or nurse specialising services, and the greater number of outpatient visits that were required for patients treated with IMF. In addition the use of IMF significantly increased the time patients spent off work. PMID- 1742261 TI - A technique for control of the condylar head during open reduction of the fractured mandibular condyle. AB - Open reduction of fractures of the neck of the mandibular condyle may be technically difficult. Control of the proximal fragment may be achieved by insertion of a Moule pin into the condylar neck. This facilitates retrieval of the condylar head and alignment of the bone fragments which are essential components of the technique. Accurate anatomical reduction and stabilisation of the fracture simplifies the technique of miniature plate fixation. PMID- 1742262 TI - Titanium mesh (TiMesh) osteosynthesis: a fast and adaptable method of semi-rigid fixation. AB - Titanium mesh has been used in the USA for the fixation of fractures of the facial skeleton since the Vietnam war. Despite the increasing use of titanium mesh osteosynthesis for trauma, orthognathic and reconstructive surgery in the USA, it is only in recent years that it has gained acceptance in Europe. This paper appraises the original titanium mesh osteosynthesis system (TiMesh) in a wide range of surgical contexts in the maxillofacial region. It has been found to be quick and reliable in placement, highly adaptable and to have considerably reduced the operating time. Its further potential advantages in reducing stress shielding and improving functional bone healing due to its semi-rigid nature are discussed. PMID- 1742263 TI - Screw fixation after mandibular sagittal split osteotomy: an intra-oral approach. AB - Intra-oral, rigid, non-compressive fixation was used in a feasibility study in 10 consecutive sagittal split osteotomies using two 3.5 or 2.7 mm diameter AO screws on each side. Seven patients were prognathic, three were retrognathic, and two had severe mandibular asymmetry. Lower third molars were removed concurrently in three patients. Horizontal and vertical stability was assessed by means of repeated, digitised cephalometry before operation, at 24-48 h and at 6 months. Intermaxillary fixation (IMF) was necessary during the first 48 h in one patient where the lingual fragments were too small. Intermaxillary elastics were used later in three patients. This method was straightforward, reliable, required no skin incisions and stability was similar to that following the use of transbuccal screw fixation. Mean horizontal relapse at 6 months (0.6 mm; maximum: 1.5 mm) was 8% of operative movement. Unsatisfactory occlusion (anterior open bite) necessitated removal of screws at 28 days in one patient. This was carried out intra-orally under local anaesthesia. These results suggest that stable, screw fixation for sagittal split osteotomies can be achieved without recourse to an external approach. PMID- 1742264 TI - Pre-tapped and self-tapping screws in children's mandibles. A scanning electron microscopic examination of the implant beds. AB - One hundred 2 mm AO miniscrews were inserted into the mandibles of eight fresh cadavers aged 8 to 12 years. Scanning electron microscopic examination of the implant beds showed cracks and accumulated bone material, as well as signs of crushing and shearing stress, regardless of whether the screws were pre-tapped or not. When, during screw insertion, the axis of the screw deviated by at least 10 degrees from the axis of the tap, two intersecting threads resulted. It is concluded that during osteosynthesis in child mandibles pre-tapping is not recommended. PMID- 1742265 TI - Osteoblastoma: a case report and description of the access used to the retromaxillary area. AB - A case of benign osteoblastoma in the retromaxillary region which presented as chronic left sided facial pain of 3 years' duration is reported. The surgical approach to a tumour in this site is difficult and potentially severely mutilating. A transfacial access is described. PMID- 1742266 TI - The effect of pre-operative perioral skin preparation with aqueous povidone iodine on the incidence of infection after third molar removal. AB - A study was carried out to measure the incidence of dry socket and wound infection following third molar removal under endotracheal general anaesthetic. One group of patients received pre-operative preparation of the perioral skin with a 10% solution of povidine-iodine, while the other received no skin preparation. Routine skin preparation imposes a risk of contact dermatitis and necessarily involves expense. In relation to postoperative wound infection, this practise was of no benefit. The results of this study provide evidence that skin preparation with povidine-iodine prior to third molar extractions should be discontinued. PMID- 1742267 TI - Blood splashes to the eyes in oral and maxillofacial surgery, and the risks of HIV transmission. AB - The risk of transmission of HIV through blood and saliva splashes to the mucous membranes around the face is unknown. Orthopaedic surgeons are very aware of possible risks and are beginning to take appropriate precautions. This present study indicates that oral and maxillofacial surgeons have similar risk factors, and the minimal precaution of wearing protective glasses should be recommended for all intraoral and extraoral surgery. PMID- 1742268 TI - Prophylactic antibiotics for patients with artificial joints undergoing oral and dental surgery: necessary or not? AB - Prophylactic antibiotic cover for certain oral and dental procedures for patients with artificial joints is a controversial issue. This paper examines the evidence supporting the use of antibiotic cover and concludes that routinely, for the majority of patients with artificial joints, it is not justified. Certain medically compromised patients with artificial joints have a slightly increased risk of infection and, under these circumstances, antibiotic prophylaxis may be justified. The antibiotic recommended for this group is cephradine or in the case of penicillin allergy, clindamycin. Preoperative dental fitness is mandatory for all patients who are to receive artificial joints. This information will be of interest to the oral and maxillofacial surgeon in his own clinical practice, and when giving advice to local general dental practitioners. PMID- 1742269 TI - Granuloma annulare of the supra-orbital region. A case report. AB - Granuloma annulare (GA) is a relatively infrequent condition affecting the dermis or the subcutaneous tissues. The aetiology of GA is purely speculative, but links with other diseases have been reported since the condition was first described. This paper discusses the usual presentation of GA, typical sites of involvement, and reviews the histology of the subcutaneous lesions of GA. It also reports a case of a 31-year-old patient who presented to an oral surgeon with subcutaneous lesions in the right supra-orbital region. A comparison between this lesion and another histologically similar entity is drawn. The reasoning behind the eventual definitive diagnosis is explained, and a review of the literature found GA affecting the head and neck to be rare. PMID- 1742270 TI - Atypical histiocytic granuloma of the tongue: case report. AB - Primary malignant lymphomas of the tongue have rarely been described, and reported cases are usually related to the posterior part of the tongue which is rich in lymphoid tissue, forming part of Waldeyer's ring. Making a distinction between pseudolymphoma and malignant lymphoma is important. Pseudolymphoma is a benign lesion not requiring aggressive therapy. Several lesions in the oral cavity, including atypical histiocytic granuloma, angiolymphoid hyperplasia with eosinophilia, and traumatic ulcerative granuloma with stromal eosinophilia have been described as having certain microscopic features similar to those of pseudolymphoma. Atypical histiocytic granuloma is not associated with systemic disease or dissemination and heals spontaneously despite its microscopic appearance. PMID- 1742271 TI - Intra-oral lipomata in association with congenital anomalies: a variant of Mohr's syndrome? AB - Two cases of intra-oral lipomata occurring in association with congenital anomalies are reported. These appear to be the first such cases described, in what appears to be a variant of Mohr's syndrome. PMID- 1742272 TI - The transcoronoid threaded wire: an aid to mandibular reconstruction. PMID- 1742273 TI - Merkel cell tumour. PMID- 1742274 TI - Traumatic aneurysms of the internal maxillary artery. PMID- 1742275 TI - DNA binding specificity of homeodomains. PMID- 1742276 TI - Design, chemical synthesis, and expression of genes for the three human color vision pigments. AB - Color vision in humans is mediated by three pigments from retinal cone photoreceptor cells: blue, green, and red. We have designed and chemically synthesized genes for each of these three pigments. The genes were expressed in COS cells, reconstituted with 11-cis-retinal chromophore, and purified to homogeneity using an immunoaffinity procedure. To facilitate the immunoaffinity purification, each pigment was modified at the carboxy terminus to contain an additional eight amino acid epitope for a monoclonal antibody previously used to purify bovine rhodopsin. The spectra for the isolated pigments had maxima of 424, 530, and 560 nm, respectively, for the blue, green, and red pigments. These maxima are in excellent agreement with the maxima previously observed by microspectrophotometry of individual human cone cells. The spectra are the first to be obtained from isolated human color vision pigments. They confirm the original identification of the three color vision genes, which was based on genetic evidence [Nathans, J., Thomas, D., & Hogness, D.S. (1986) Science 232, 193]. PMID- 1742277 TI - Photolysis intermediates of human rhodopsin. AB - Photochemical studies were conducted on human rhodopsin at 20 degrees C to characterize the intermediates which precede the formation of metarhodopsin II, the trigger for the enzyme cascade mechanism of visual transduction. Human rhodopsin was prepared from eyes which had previously been used for corneal donations. Time resolved absorption spectra collected from 10(-8) to 10(-6) s after photolysis of human rhodopsin in detergent suspensions displayed biexponential decay kinetics. The apparent lifetimes obtained from the data are 65 +/- 20 and 292 +/- 25 ns, almost a factor of 2 slower than the corresponding rates in bovine rhodopsin. The spectra can be fit well using a model in which human bathorhodopsin decays toward equilibrium with a blue-shifted intermediate (BSI) which then decays to lumirhodopsin. Spectra and kinetic rate constants were determined for all these intermediates using a global analysis which showed that the spectra of the human intermediates are remarkably similar to bovine intermediates. Microscopic rate constants derived from this model are 7.4 x 10(6) s-1 for bathorhodopsin decay and 7.5 x 10(6) s-1 and 4.6 x 10(6) s-1 for the forward and reverse reactions of BSI, respectively. Decay of lumirhodopsin to later intermediates was studied from 10(-6) to 10(-1) s after photolysis of rhodopsin in human disk membrane suspensions. The human metarhodopsin I in equilibrium metarhodopsin II equilibrium appears to be more forward shifted than in comparable bovine studies. PMID- 1742278 TI - Structure of the pure-spermine form of Z-DNA (magnesium free) at 1-A resolution. AB - We describe the three-dimensional X-ray structure of a complex of spermine bound to a Z-DNA duplex, [d(CGCGCG)]2, in the absence of any inorganic polyvalent cations. We have crystallized the DNA hexamer d(CGCGCG) in the exclusion of magnesium and other polyvalent ions and solved its structure at 1.0-A resolution. In the crystal of this pure-spermine form of Z-DNA, the relative orientation, position, and interactions of the DNA differ from the arrangement uniformly observed in over a dozen previously reported Z-DNA hexamers. Moreover, the conformation of the Z-DNA hexamer in this structure varies somewhat from those found in earlier structures. The DNA is compressed along the helical axis, the base pairs are shifted into the major groove, and the minor groove is more narrow. The packing of spermine-DNA complexes in crystals suggests that the molecular basis for the tendency of spermine to stabilize compact DNA structures derives from the capacity of spermine to interact simultaneously with several duplexes. This capacity is maximized by both the polymorphic nature and the length of the spermine cation. The length and flexibility of spermine and the dispersion of charge-charge, hydrogen-bonding, and hydrophobic bonding potential throughout the molecule maximize the ability of spermine to interact simultaneously with different DNA molecules. PMID- 1742279 TI - Stimulation of DNA polymerase alpha activity by microtubule-associated proteins. AB - Microtubule-associated protein 2 (MAP2) isolated from porcine brains stimulated the activity of DNA polymerase alpha immunopurified from calf thymus or human lymphoma cells, in a dose-dependent manner. This stimulation was pronounced when activated DNA or poly(dA).(dT)10 was used as the template-primer. DNA polymerase alpha bound to a MAP2-immobilized column, whereas preincubation of the enzyme with unbound MAP2 prevented binding to the column. These events suggested that a physical binding occurred between the polymerase and MAP2. Kinetic analyses revealed that MAP2 decreased the Km value of the polymerase for deoxyribonucleotides, irrespective of the species of template-primer. A concomitant increase in Vmax was observed; however, the extent of the increase depended on the species of template-primer. MAP2 also decreased the Km value of the polymerase for template-primers when activated DNA of poly(dA).(dT)10 was used as the template-primer. Product analyses showed that MAP2 did not significantly alter the processivity of the polymerase and the increment of Vmax is considered to be due to an increase in the frequency of initiation of DNA synthesis. The stimulation by MAP2 occurred specifically in the activity of DNA polymerase alpha, but not DNA polymerases beta, gamma, and I from Escherichia coli. Other MAPs, tau and 190-kDa MAP, could substitute for MAP2. Thus, the specific stimulation of DNA polymerase alpha by MAPs supports the notion of a possible involvement of MAPs or MAP-like proteins in DNA replication, in vivo. PMID- 1742280 TI - Interaction of ribosomal protein S1 and initiation factor IF3 with the 3' major domain and the decoding site of the 30S subunit of Escherichia coli. AB - We have studied the effect of the binding of ribosomal protein S1 and initiation factor IF3 on the accessibility of nucleotide residues 584-1506 in the small subunit of the Escherichia coli ribosome. Protein S1 strongly decreases RNase V1 attack at G1164, in hairpin 40 of the 3' major domain, and weakly decreases DMS attack at C1302, in the central loop of the 3' major domain, and at A1503, in the 3' minor domain. It also weakly increases the DMS reactivity of A1004, in the 3' major domain, and of A901, in the central domain. Factor IF3 strongly decreases RNase V1 attack (but not dimethyl sulfate attack) at A1408, in the decoding site, and weakly protects A1500, in the 3' minor domain and near the colicin E3 cleavage site. Neomycin does not interfere with this effect of IF3, but IF3 interferes with the protective effect of neomycin against dimethyl sulfate attack at A1408. PMID- 1742281 TI - Crystal structure of the cytochrome P-450CAM active site mutant Thr252Ala. AB - The crystal structure of a cytochrome P-450CAM site-directed mutant in which the active site Thr252 has been replaced with an Ala (Thr252Ala) has been refined to an R factor of 0.18 at 2.2 A. According to sequence alignments (Nelson & Strobel, 1989), Thr252 is highly conserved among P-450 enzymes. The crystallographic structure of ferrous camphor- and carbon monoxide-bound P-450CAM (Raag & Poulos, 1989b) suggests that Thr252 is a key active site residue, forming part of the dioxygen-binding site. Mutation of the active site threonine to alanine produces an enzyme in which substrate hydroxylation is uncoupled from electron transfer. Specifically, hydrogen peroxide and "excess" water are produced instead of the product, 5-exo-hydroxycamphor. The X-ray structure has revealed that a local distortion in the distal helix between Gly248 and Thr252 becomes even more severe in the Thr252Ala mutant. Furthermore, a solvent molecule not present in the native enzyme is positioned in the dioxygen-binding region of the mutant enzyme active site. In this location, the solvent molecule could sterically interfere with and destabilize dioxygen binding. In addition, the active site solvent molecule is connected, via a network of hydrogen bonds, with an internal solvent channel which links distal helix residues to a buried Glu side chain. Thus, solvent protons appear to be much more accessible to dioxygen in the mutant than in the wild-type enzyme, a factor which may promote hydrogen peroxide and/or water production instead of substrate hydroxylation. On the basis of crystallographic and mutagenesis data, a proton delivery pathway involving residues Lys178/Arg186, Asp251, and Thr252 is proposed for wild-type P-450CAM. Coordinates of structures discussed in this paper have been submitted to the Brookhaven Protein Data Bank (Bernstein et al., 1977). PMID- 1742282 TI - Mouse pulmonary cytochrome P-450 naphthalene hydroxylase: cDNA cloning, sequence, and expression in Saccharomyces cerevisiae. AB - We have isolated a cDNA clone, Nah-2, encoding the cytochrome P-450Nah (naphthalene hydroxylase) from a mouse lung lambda ZAP cDNA library using anti cytochrome P-450Nah IgG as a probe. This same antibody selectively blocked [Nagata, K., Martin, B.M., Gillette, J.R., & Sasame, H.A. (1990) Drug Metab. Dispos. 18, 557-564] the cytochrome P-450 in mouse lung microsomes that catalyzed the conversion of naphthalene to (1R,2S)-naphthalene 1,2-oxide, which has been postulated as a causative agent in the naphthalene-induced tissue-specific necrosis of Clara cells in mouse lung. The toxic effect is seen in mouse and not in rat. The cDNA encodes a polypeptide of 491 amino acids with a molecular mass of 50 kDa. Northern blot analysis with an Nah-2-specific probe revealed that the mRNA is expressed in a species- and tissue-specific manner, present only in mouse lung and liver and not in that of rat. The mRNA encoding Nah-2 is constitutively expressed and is not induced by either phenobarbital, pyrazole, pregnenolone 16 alpha-carbonitrile, or 3-methylcholanthrene. Comparative amino acid sequence analyses with other documented members of the P-450 gene superfamily revealed that this encoded protein is in the IIF subfamily. To analyze its substrate specificity, the cDNA was inserted into the vector, pAAH5, and expressed in the Saccharomyces cerevisiae strain, AH22. The presence of cytochrome P-450Nah in the microsomes isolated from transformed cells and analyzed by Western blot was confirmed by immunocomplexing product with anti-cytochrome P450Nah IgG. Furthermore, activity toward naphthalene in the microsomes from the transformed cells established that this clone encodes a naphthalene hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742283 TI - Electrochemical and kinetic analysis of electron-transfer reactions of Chlorella nitrate reductase. AB - Assimilatory nitrate reductase (NR) from Chlorella is homotetrameric, each subunit containing FAD, heme, and Mo-pterin in a 1:1:1 stoichiometry. Measurements of NR activity and steady-state reduction of the heme component under conditions of NADH limitation or competitive inhibition by nitrite suggested intramolecular electron transfer between heme and Mo-pterin was a rate limiting step and provided evidence that heme is an obligate intermediate in the transfer of electrons between FAD and Mo-pterin. In addition to the physiological substrates NADH and nitrate, various redox mediators undergo reactions with one or more of the prosthetic groups. These reactions are coupled by NR to NADH oxidation or nitrate reduction. To test whether intramolecular redox reactions of NR were rate-determining, rate constants for redox reactions between NR and several chemically diverse mediators were measured by cyclic voltammetry in the presence of NADH or nitrate. Reduction of ferrocenecarboxylic acid, dichlorophenolindophenol, and cytochrome c by NADH-reduced NR was coupled to reoxidation at a glassy carbon electrode (ferrocene and dichlorophenolindophenol) or at a bis(4-pyridyl) disulfide modified gold electrode (cytochrome c), yielding rate constants of 10.5 x 10(6), 1.7 x 10(6), and 2.7 x 10(6) M-1 s-1, respectively, at pH 7. Kinetics were consistent with a second-order reaction, implying that intramolecular heme reduction by NADH and endogenous FAD was not limiting. In contrast, reduction of methyl viologen and diquat at a glassy carbon electrode, coupled to oxidation by NR and nitrate, yielded similar kinetics for the two dyes. In both cases, second-order kinetics were not obeyed, and reoxidation of dye-reduced Mo-pterin of NR by nitrate became limiting at low scan rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742284 TI - Identification of a new binding protein for crotoxin and other neurotoxic phospholipase A2s on brain synaptic membranes. AB - Crotoxin and other neurotoxic phospholipase A2s exert neurotoxicity by acting primarily at the presynaptic level. Strong binding of crotoxin and several others to synaptic membranes has been demonstrated previously. In this study we used simple chemical cross-linking techniques to identify the neuronal membrane molecules involved in the binding of these toxins. After 125I-crotoxin had bound to synaptosomes from guinea pig brain, treatment with disuccinimidyl suberate, disuccinimidyl dithiobis(propionate) or ethylene glycol bis(succinimidyl succinate) resulted in the formation of a predominant radioactive conjugate of approximately 60 kDa, which was different from the conjugate formed by photoaffinity labeling technique in a previous report. The membrane component in the conjugate was shown to be a single-chain protein of approximately 45 kDa. In subfractions of synaptosomes, this binding protein was mostly found in the synaptic membrane fraction and was not present in the mitochondrial fraction. Plasma membranes from several nonneural tissues also did not contain this binding protein. Unmodified crotoxin inhibited the formation of this adduct with an IC50 of around 1 x 10(-8) M. Mojave toxin and some other phospholipase A2s were also highly inhibitory to this conjugation, and notexin and others were less effective, while beta-bungarotoxin and pancreatic PLA2 were totally ineffective. We concluded that a new protein of 45 kDa specifically present in neuronal membranes is another major molecule responsible for the binding of crotoxin and other phospholipase A2s. PMID- 1742285 TI - Unrestrained pride: development of a protocol for a restraint free environment. AB - This article describes one facility's experience in attempting to enhance compliance with nonrestraint policy. The importance of policy implementation is emphasized, particularly as it relates to nursing care. In response to a study which revealed that a large number of wheelchair restraints were being applied indiscriminately, the extended care facility developed a flow chart in order to facilitate appropriate decision making and assessment regarding safety and restraints. The flow chart/protocol was created to bridge the gap between the conceptual policy level and the procedures for restraint application and removal. It is based on the nursing process and is dependent on ongoing assessment of the resident's status. A survey carried out one year after the initial, pre intervention survey revealed that only 6.4% of residents were restrained using wheelchair lap belts, compared to the previous 26%, identified as problematic at the outset of the study. PMID- 1742286 TI - Admission criteria for a special care unit for residents with dementia. AB - The recent trend in caregiving for cognitively impaired residents has been to provide special care units. One of the questions in establishing a special unit is deciding on admission criteria. What range of impairment will benefit the most from this type of environment? This paper reports on how one facility developed specific assessment criteria for admission to a special unit. The goals were to identify potential residents for the unit, reduce subjectivity in the assessment process and be able to screen both residents and community applicants. Results of the screening instrument demonstrated that it was effective in identifying a range of impairments, it screened out the cognitively well and long standing psychiatric disorders, and also demonstrated that a pre-set bias did exist as to who should be admitted. PMID- 1742287 TI - The family support group. AB - This article was written as an informative guide for health care professionals. It offers a comprehensive view of the implementation of a special program designed for families and/or friends only--known as "The Family Support Group". Initiated in a Long Term Care Facility the author provides a descriptive analysis for identifying the needs of the residents' families and/or friends. The rationale leading to the initial development of the group and the special mechanisms it provides as a quality assurance measure are explored. It is the writer's hope that others will be able to incorporate this idea to their facilities regardless of whether it is long term or an acute care setting. PMID- 1742288 TI - Hospital-based nursing research programs: a requirement for progress. AB - Research has resulted in improvement of the quality of patient care, greater job satisfaction for nursing service personnel, and better utilization of personnel. Facilitation of research has been accomplished through the establishment of nursing research programs in hospitals. However, the current climate of economic restraint gives rise to the risk that research in hospitals will be viewed as a "budget luxury" which can be eliminated early in the financial review process. The need for a nursing research program as part of a modern hospital organization is defended in this paper. The benefits of such a program and an infrastructure supportive of nursing research are described. PMID- 1742289 TI - Issues in long term care. PMID- 1742290 TI - Nurses' perception of quality of care. AB - Identifying appropriate indicators and barriers can be a difficult task for the nurse administrator. This manuscript summarizes a qualitative study which examines staff perceptions of these issues. Feedback from the nursing staff was specific and helpful in improving systems related to quality of care. PMID- 1742291 TI - Session I: Pediatric heart transplantation in historical perspective. PMID- 1742292 TI - Session II: Cardiac replacement in infants and children: indication and limitations. PMID- 1742293 TI - Session III: Initiating the pediatric heart transplantation process. PMID- 1742294 TI - Session IV: Surgical techniques in pediatric heart transplantation. PMID- 1742295 TI - Session V: The neonatal immune system: window of opportunity? PMID- 1742296 TI - Session VI: Rejection/infection: the limits of heart transplantation success. PMID- 1742297 TI - Session VIII: Pediatric heart transplantations: the world experience. PMID- 1742298 TI - Session IX: Social and ethical controversies in pediatric heart transplantation. PMID- 1742299 TI - Postpalatoplasty decrease in respiratory dead space in young children. AB - In 20 children with cleft palates age 1.5 to 2 years, respiratory parameters were evaluated before, 15 minutes after, and 1 hour after palatoplasty. The dead space (VD) in the palatoplasty group decreased from 25.2 +/- 4.7 ml preoperatively to 12.3 +/- 9.1 ml postoperatively. This decrease improved respiratory efficiency. A significant difference was found postoperatively in the partial pressure of CO2 in arterial blood (PaCO2) between the palatoplasty and control groups. No significant differences were found in base excess (BE), arterial pH, pulmonary shunt ratio, and the alveolar-arterial O2 difference (A-aDO2) between the groups pre- and postoperatively. This finding indicated that temporary respiratory failure may exist postoperatively; the phenomena were improved in the recovery room. Since lung compliance and airway resistance may also participate in the decrease in VD, further evaluation of these factors are necessary. PMID- 1742300 TI - Accuracy of information reported by parents and children evaluated by a cleft palate team. AB - Children with palatal clefts and their parents were interviewed to determine what information they had about the cleft and its management. Their responses were compared with the standards of 17 team members from seven disciplines. Both parent and child were consistently provided information about clefts that they were expected to remember. The children's responses met the standards 67 percent of the time. Their parents' responses met the standards 80.6 percent of the time. Parents accurately predicted their children's responses 92 percent of the time. PMID- 1742301 TI - Biologic basis for a risk assessment model for cleft palate. AB - A biologic model for palatogenesis is presented, intended as a basis for risk assessment. It comprises a sequence of developmental stages: growth and migration of neural crest cells, downward growth of palatal buds, elevation of palatal shelves, and differentiation of the epithelium followed by shelf fusion. Several events representing these stages and amenable to mathematical translation may be measurable in the form of biomarkers such as DNA and protein synthesis, phospholipid metabolism, and signal transducing systems. Interrupting components of the model will result in cleft palate. Teratogens with known mechanisms of action are compared with the model. The quantitative risk of cleft palate is conceived as a sequence of mathematical probabilities that any stage of the model runs an abnormal course. Stage-specific probabilities are determined by a chemical's potency and dose, and by duration of exposure and gestational age. Species or strain sensitivity may be expressed as quantitative differences in model parameters. Although the model is designed for cleft palate, the risk model may also estimate a multiple response risk to the same exposures. PMID- 1742302 TI - Self-concept of children and adolescents with cleft lip and/or palate. AB - The self-concept of 105 children (8 to 11 years) and adolescents (12 to 18 years) with cleft lip and/or palate (CLP) was studied using the Piers-Harris Children's Self-Concept Scale and selected demographic and medical variables. Results indicated that most (98%) of children had average or above average self-concept scores. Further analysis, however, demonstrated an interaction between age and gender: adolescent girls experienced a more negative self-concept in comparison to younger girls and adolescent boys experienced a more positive self-concept in comparison to younger boys. In addition, popularity cluster scores for all children were below the mean for the normed population. Because children with CLP have additional difficulties (i.e., facial disfigurement, speech and language deficits, multiple surgeries), professionals should intercede to prevent or interrupt negative psychosocial outcomes, particularly for adolescent girls. PMID- 1742303 TI - Psychosocial adjustment in children with hemifacial microsomia and other craniofacial deformities. AB - Psychosocial adjustment was evaluated in different groups of children with craniofacial deformities in order to examine the relationships between symmetry, functional impairments, and social adaptation. Thirty patients, ages 6 through 16 years, were assessed using a battery of standard psychologic measures including Human Figure Drawing, Tasks of Emotional Adjustment, and Children's Depression Inventory. Parents and teachers also provided ratings of the children's functioning using the Child Behavior Checklist (parent and teacher forms). Scores on the outcome measures were summarized with descriptive statistics and then multivariate analyses of variance were conducted to determine the differences in psychosocial development between children with symmetric versus asymmetric craniofacial deformities and between the presence or absence of a functional impairment in children with craniofacial deformities. The results indicate that children with symmetric craniofacial deformities score poorer on measures of psychosocial adjustment than children with asymmetric deformities (F = 3.20, p less than 0.015); however, differences among the groups with or without functional impairments were not significant. PMID- 1742304 TI - Misarticulation caused by abnormal lingual-palatal contact in patients with cleft palate with adequate velopharyngeal function. AB - Misarticulations produced by three patients with cleft palate (2 isolated cleft palate; 1 unilateral cleft lip, alveolus, and palate) who attained adequate velopharyngeal function and normal palatal vault by early surgical repairs were examined using electropalatography (EPG) and sound spectrography (SG). Common characteristics of lingual-palatal contact in which the contact area was broader and/or was more posterior than normal were observed. These misarticulations can be divided into three types based on the direction of the breath emission: palatalized misarticulation (in which air passes along the midline of the palate), lateral misarticulation (in which air flows laterally through the occluded dental arch), and nasopharyngeal misarticulation (in which air flows out the nose). These three are considered to be similar to intractable posterior pattern of articulation in cleft palate patients previously reported. However, these types of misarticulations can be produced by cleft patients who have achieved adequate velopharyngeal function and normal palatal vault. PMID- 1742305 TI - Craniofacial asymmetries in shunt-treated hydrocephalic children. AB - The degree and direction of craniofacial asymmetry in the frontal plane was studied in a sample of 26 shunt-treated hydrocephalic children aged 5 to 18 years. Thirteen of the children had the regulating shunt fixed on the right side of the head and 13 on the left. The shunt had usually been inserted during the first years of life. An age- and sex-matched group of healthy school children and students served as controls for cephalometric assessment by means of linear and angular measurements. Considerable craniofacial asymmetry was found in the shunt treated hydrocephalic children, the direction of asymmetry being related to the laterality of the regulating shunt device. The most marked asymmetric changes were recorded in the maxillary and mandibular regions, probably due to the adaptive nature of these regions. PMID- 1742306 TI - Epidemiology of oral clefts in a large South American sample. AB - A total of 849,381 newborn children were examined during the years 1967 to 1981, in 56 hospitals of eight countries, in the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Of these, 741 had a cleft lip with or without a cleft palate (CL +/- P), yielding a global prevalence of 0.87 per thousand, and 115 had cleft palate (CP) only (frequency: 0.13 per thousand). CP frequencies by country and by year were essentially homogeneous, but those for CL +/- P showed heterogeneity by country (but no temporal trends). Patients thus ascertained, with matched, appropriate controls, have been subjected to a detailed epidemiologic study. For CP, only the sex ratio deviated from the control values; but for CL +/- P the marked divergence in sex ratio was accompanied by differences in the two series on the frequency of twin births, birth weight, neonatal survival, birth order, medicine use, and occurrence of acute or chronic illnesses during the first trimester of pregnancy. Lack of agreement of these results with previous data may be due to different types of patient ascertainment, sample sizes, and methods of analysis. PMID- 1742307 TI - Characteristics of new patients at Illinois cleft palate teams. AB - The Illinois Association of Craniofacial Teams (IACT) surveyed all new patient visits to member teams in an effort to assess the needs of patients in Illinois. The survey determined the number of patients, their age at initial visit, the location and status of their defect, and their history of team visits. Four hundred eighty new patient visits were recorded. The number of patients was substantially lower than expected, and the large majority of older children seeing a team for the first time had repaired defects. It is concluded that the main opportunity for improving the quality of care for patients with clefts in Illinois may be in increasing the use of cleft palate teams. PMID- 1742308 TI - Development of a method for rating nasolabial appearance in patients with clefts of the lip and palate. AB - Comparison of the outcome of treatment of patients with clefts of the lip and palate can yield valuable pointers for discriminating between beneficial and harmful procedures. The development of a standardized rating scheme to assess the facial appearance of these patients is described. The rating scheme can be used in conjunction with conventional cephalometric analysis and dental arch evaluation. A method is described in which the nasolabial area is masked, thus reducing the influence of the surrounding facial features since it is shown that judges are influenced by general facial attractiveness. An ordinal scale has been evaluated in which four features of the nose and lip are assessed separately and in total by a panel of judges. The nasolabial profile, the nasal symmetry, the nasal form, and vermilion border were assessed using a 5-point scale. Acceptable pooled levels of reliability and reproducibility were obtained. This standardized rating system may be used to differentiate treatment outcome in patients from different treatment centers. PMID- 1742309 TI - Postnatal craniofacial skeleton development following a pushback operation of patients with cleft palate. AB - A longitudinal growth study of the craniofacial skeleton in 52 (19 males, 33 females) Danish individuals with cleft palates was performed. Thirty (13 males, 17 females) had clefts of the soft palate only or clefts extending into the posterior third of the hard palate. Twenty-two (6 males, 16 females) had more extensive clefts including up to two-thirds of the hard palate. The cleft was closed with a pushback operation at 22 months of age. Orthodontic treatment was included in the early mixed dentition. Lateral cephalometries were obtained at 5, 8, 12, 16, and 21 years of age. Twenty-four variables were digitized and analyzed. The results indicated that patients with more extensive clefts demonstrated significantly smaller anterior cranial base length (N-S), total cranial base length (N-Ba), maxillary dentoalveolar base length (A-PMP), mandibular length (Cd-Pgn), upper anterior and posterior facial heights (N-ANS and P-PMP), and total facial height (N-Gn). Patients with the more extensive clefts reached maximum growth spurt later than patients with less extensive clefts in all dimensions except the A-PMP and the lower and total facial heights. PMID- 1742310 TI - Pressure-flow measurements for selected oral and nasal sound segments produced by normal adults. AB - Pressure-flow data are often used to provide information about the adequacy of velopharyngeal valving for speech. However, there is limited information available concerning simultaneous pressure-flow measurements for oral and nasal sound segments produced by normal speakers. This study provides normative pressure, flow, and velopharyngeal orifice area measurements for selected oral and nasal sound segments produced by 10 male and 10 female adult speakers. An aerodynamic categorization scheme of velopharyngeal function, including one typical category and three atypical categories (open, closed, and mixed) is proposed. PMID- 1742311 TI - Developmental correlates of midfacial components in a normal and cleft lip and palate human fetal sample. AB - Midfacial hypoplasia in patients with complete clefts of the lip and palate is considered to be the result of congenital dysmorphogenesis combined with surgical effects. The present study describes congenital correlates of midfacial hypoplasia by examining the relationships between premaxillary size and a number of adjacent oronasal capsular components in a sample of second trimester normal and complete cleft fetal specimens. Midfacial relationships from previously published data from 3-D computer reconstructions of histologic material were assessed by multiple regression and path analyses. Stepwise multiple regression analysis revealed that the combination of age (body size) and nasal septal length were the best predictor variables of premaxillary length and accounted for 90 percent and 93 percent (p less than .01) of the variance in normal and cleft fetal specimens, respectively. Tongue length was seen to slightly increase the R2 values in the cleft, but not the normal sample. Path analysis results revealed that with body size held constant, nasal capsule volume explained only 3 percent of premaxillary variance, while septal length accounted for approximately 45 percent of the variance (p less than .05). Results show that the relationships of the midfacial components in the cleft fetal sample closely followed normal second trimester midfacial growth patterns and suggest that the septal-traction model may be a more parsimonious and primary explanatory mechanism of early midfacial growth than the functional matrix model in both normal and complete cleft fetal specimens. PMID- 1742312 TI - Comparison between multiview videofluoroscopy and nasendoscopy of velopharyngeal movements. AB - The videofluoroscopic and nasopharyngoscopic observations of velopharyngeal movements during speech were compared in 80 subjects with hypernasal speech. An endviewing flexible fiberoptic endoscope was used for nasopharyngoscopic examination. This failed to demonstrate movements of the lateral pharyngeal walls that were videofluoroscopically documented in one third of the patients. In the cases of disagreement, the angle of view was impaired because of the presence of adenoid tissue. The misinterpretation at nasopharyngoscopy was explained by an unfavorable observation position of the flexible scope and failure to pass it further into the pharynx. Conclusions are satisfactory that videofluoroscopy is an indispensable procedure for assessing velopharyngeal function. PMID- 1742313 TI - Development of scales of severity of facial cleft impairment. AB - The reliability and validity of human judgments in rating the severity of cleft related facial impairment were examined in this series of studies. The goal of the research was to develop scales for rating the severity of facial cleft impairment using psychophysical methods for measuring human judgment. The principle findings were: (1) Four photographic categorized scales with high inter group reliability and satisfactory content and construct validity were developed; (2) Raters used objective stimulus characteristics of the face to scale impairment; (3) Ratings of facial attractiveness decreased as the severity of impairment increases; (4) Full face ratings of the severity of impairment correlated highly with ratings of the same photographs cropped below the eyes. The implications of these findings for clinical and research application are discussed. PMID- 1742314 TI - Mandible, tongue, and airway in Pierre Robin sequence: a longitudinal cephalometric study. AB - The purpose of this retrospective longitudinal cephalometric study was to analyze size, growth, and relations of the mandible, tongue, and airway in the isolated, nonsyndromic Pierre Robin Sequence (PRS) infant. The objective was to understand better the early morphologic changes that occur in these structures. The data were obtained from lateral cephalometric radiographs taken in the first 2 years of life on 17 PRS infants, 26 isolated cleft palate (CP), and 26 normal control (N) infants. Mean values of each variable were compared using a univariate analysis of variance. A multivariate discriminant function analysis (DFA) was also used to characterize group differences. The three groups were distinct throughout the period of study. Differences were greater at the earliest age and the distinction was greater between the PRS and N infants with the CP infant in between, but having more similarity to the PRS infant. Initially, the PRS infant had a shorter tongue and mandibular length, narrower airway, smaller tongue area and the hyoid position was more posterior and inferior as compared to N. The tongue shape and position were specific to the PRS infants. This group distinction diminished with age and resulted from an increased mandibular growth rate in the PRS infant. These findings support the hypothesis of "partial mandibular catch-up growth" in the PRS infant. The increased growth rate in the PRS infant improved the airway dimension, which might be partly responsible for the natural resolution of the respiratory distress. This increased growth rate did not allow for the various structures to reach values equal to normal. PMID- 1742315 TI - The effect of apo E secretion on lipoprotein uptake in transfected cells. AB - To investigate the role of apolipoprotein E (apo E) secreted by peripheral tissues in local lipoprotein metabolism, we developed a cell strain that constitutively produced and secreted apo E. A fusion plasmid containing rat apo E genomic DNA under control of mouse metallothionein promotor was constructed and transfected into Chinese hamster ovary cells. A stable transformant designated CHO-MAEII constitutively secreted rat apo E mainly in the form of sialylated free protein. The secretion was further enhanced by metal induction up to 1 micrograms apo E/ml per 12 h. When incubated with 125I-labeled very low density lipoprotein (125I-VLDL) at 37 degrees C, CHO-MAEII took up and degraded 125I-VLDL with higher affinity than control cells. Furthermore, considerable amount of methylated 125I VLDL was degraded by CHO-MAEII, while no methylated 125I-VLDL was degraded by control cells. No significant differences were found in the uptake of 125I-LDL. The data indicated that apo E molecules secreted by CHO-MAEII were transferred to 125-VLDL particles, which caused a higher affinity of these particles for LDL receptors on the cells. It is suggested that apo E secreted from peripheral tissues enhances the uptake of lipoproteins by themselves or by surrounding cells in the local environment which demand cholesterol and express LDL receptors. CHO MAEII was a good model for these 'auto- or paracrine-like functions' of apo E. PMID- 1742316 TI - The apolipoprotein A-I binding protein of placenta and the SP-40,40 protein of human blood are different proteins which both bind to apolipoprotein A-I. AB - A complement-associated protein SP-40,40, which is a normal constituent of human blood, binds to the main apoprotein, apoA-I, of high density lipoprotein (HDL). This protein, which is identical to apolipoprotein J, was compared to another apoA-I binding protein purified from human placenta. Immunologically the two apoA I binding proteins are different. PMID- 1742317 TI - Physico-chemical characterization of Intralipid emulsions. AB - Fat emulsions containing soy triacylglycerols (100-300 g/l) and egg-yolk phospholipids (12 g/l) are often used for intravenous feeding. Previous studies have shown that these emulsions contain chylomicron-like emulsion particles of diameters of 300-400 nm and excess phospholipids aggregated as vesicles (liposomes), which remain in the infranatant upon floatation of the emulsion particles by ultracentrifugation. This work is devoted to the characterization of the commercial lipid emulsions commonly denoted Intralipids, with special emphasis on the presently ill-defined liposomes. The lipid particles composing commercial lipid emulsions (10%, 20% and 30% Intralipids, Kabivitrum Nutrition) were characterized by the combined use of physical and chemical methods. Each of the emulsions was fractionated by ultracentrifugation in saline into a 'cream' layer which floats to the top of the dispersion upon ultracentrifugation and a relatively transparent infranatant. The cream layer contains large emulsion particles of diameters ranging from 300 to 400 nm, in agreement with theoretical considerations based on their chemical composition as determined by chemical analysis. The infranatants contain about 1 g/l triacylglycerols in addition to phospholipids (from 7.2 g/l in 10% Intralipid to 2.4 g/l in 30% Intralipid) in the form of smaller particles of 70-100 nm diameter. Cryo-transmission electron microscopy shows that the infranatants contain vesicles (mostly unilamellar) at the side of residual small emulsion particles. This conclusion is also consistent with the distribution of phospholipids between outer and inner lamellae, as determined by 31P-NMR. PMID- 1742318 TI - The oxidative modification of low density lipoprotein by nonenzymatically glycated peptide-Fe complex. AB - Glycated polylysine, a model of glycated peptide, produces Fe(3+)-chelated compound, which could be converted to an active form in a nonenzymatic process. The exposure of human low density lipoprotein (LDL) to the active glycated polylysine-iron complex caused lipid peroxidation significantly higher than LDL exposed to Fe3+, accompanied by formation of fluorescence compound in apoprotein B (Ex.max. 360 nm, Em.max. 435 nm). Highly modified LDL, which can be judged by an obvious increase of fluorescence compound, could be easily endocytized by rat peritoneal macrophages. alpha-Tocopherol or probucol possessed powerful inhibitory action against active glycated polylysine-iron complex-induced lipid peroxidation of LDL. Each of intrinsic proteins tested, such as apotransferrin, ceruloplasmin and albumin, at the concentration of normal levels of human blood or at the lower levels, also exhibited inhibitory action on the lipid peroxidation of LDL. PMID- 1742319 TI - Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes. AB - In primary culture of rat hepatocytes, simvastatin, a powerful HMGCoA reductase inhibitor, inhibited acetate incorporation into cellular and secreted cholesterol and cholesteryl-esters, without any significant effect on triacylglycerol synthesis and secretion. When applied to the culture for 24 h at 10(-7) M, a concentration shown to inhibit cholesterol synthesis by 61%, simvastatin increased apolipoprotein BH and BL synthesis and secretion and strongly decreased apolipoprotein AI synthesis and secretion whereas apolipoprotein AIV remained unaffected. The synthesis and secretion of apolipoprotein E was only slightly affected in contrast with other situations where cholesterol synthesis decreased. All of these modifications occurred at a post-transcriptional level, as the corresponding messenger RNAs of the apolipoproteins did not vary. These results suggest that either the drug itself or variations in cholesterol synthesis might be involved in apo B and apo AI synthesis and secretion. PMID- 1742320 TI - Metabolism of polyunsaturated (n-3) fatty acids by monkey seminal vesicles: isolation and biosynthesis of omega-3 epoxides. AB - Monooxygenases of monkey seminal vesicles can metabolize arachidonic acid (20:4(n 6)) by w3-hydroxylation to 18(R)-hydroxyeicosatetraenoic acid (18(R)-HETE) and eicosapentaenoic acid (20:5(n-3)) to 17,18-dihydroxyeicosatetraenoic acid (Oliw, E.H. (1989) J. Biol. Chem. 264, 17845-17853). The present study aimed to further characterize the oxygenation of (n-3) polyunsaturated fatty acids. 14C-Labelled 22:6(n-3), 20:5(n-3), 20:4-(n-3) and 18:3(n-3) were incubated with microsomes of seminal vesicles of the cynomolgus monkey, NADPH and a cyclooxygenase inhibitor, diclofenac, and the main metabolites were identified by capillary gas chromatography-mass spectrometry. 22:6(n-3) was slowly metabolized to 19,20 dihydroxy-4,7,10,13,16-docosapentaenoic acid, while 20:5(n-3), 20:4(n-3) and 18:3(n-3) were metabolized more efficiently to the corresponding w4,w3-diols. The w3 epoxides, which were obtained from 20:5(n-3) and 18:3(n-3), were isolated in the presence of an epoxide hydrolase inhibitor, 1(2)epoxy-3,3,3-trichloropropane, and the geometry of the epoxides was determined to be 17S, 18R and 15S, 16R, respectively. While 20:5(n-3) was metabolized almost exclusively to the epoxide and diol pair of metabolites, 18:3(n-3) was metabolized not only to the w3 epoxide and the corresponding diol, but also to the w2 alcohol, 17(R)-hydroxy 9,12,15-octadecatrienoic acid. 22:6(n-3) and 5,8,11,14-eicosatetraynoic acid inhibited the biosynthesis of 18(R)-HETE from arachidonic acid (IC50 0.16 and 0.14 mM, respectively). In comparison with 20:4 or 18:3(n-3), 18:1(n-9) and 22:5(n-6) appeared to be slowly metabolized by seminal monooxygenases, while 18:2(n-6) was converted to the w3 alcohol and to smaller amounts of the w2 alcohol (4:1). Together, the results indicate that the w3-hydroxylase and w3 epoxygenase enzyme(s) metabolize 20:4(n-6) and 20:5(n-3) almost exclusively to the w3(R) alcohol and the w3(R, S) epoxide, respectively, while longer and shorter fatty acids either are poor substrates or metabolized with a lesser degree of position specificity. PMID- 1742321 TI - Interactive effects of dietary (n-3) polyunsaturated fatty acids and chronic ethanol intoxication on synaptic membrane lipid composition and fluidity in rats. AB - The influence of dietary polyunsaturated fatty acids on fatty acid composition, cholesterol and phospholipid content as well as 'fluidity' (assessed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) probes) of brain synaptic plasma membranes (SPM) and their interactions with chronic ethanol effects were studied in rats fed for two generations with diets either devoid of (n-3) fatty acids (sunflower oil diet), rich in alpha-linolenic acid (soya oil diet) or in long chain (n-3) fatty acids (sunflower + cod liver oil diet). Results were compared with rats fed standard lab chow. Sunflower oil led to an increase in the (n-6)/(n-3) ratio in the membranes with an increase of the 'fluidity' at membrane apolar level; sunflower + cod liver oil decreased the (n 6)/(n-3) ratio without affecting membrane 'fluidity' while no difference was seen between the SPM of rats fed soya oil and standard diet. After 3 weeks alcohol intoxication in rat fed the standard diet: oleic alpha-linoleic acids and cholesterol levels were increased, arachidonic acid and the double bond index/saturated fatty acids were decreased and there was a decrease of 'fluidity' in the lipid core of the SPM. Soya oil almost totally abolished these usually observed changes in the SPM fatty acids composition but increased oleic acid and cholesterol without any change in fluidity. Sunflower oil led to the same general alterations of fatty acid as seen with standard diet but to a greater extent, with decrease of the 'fluidity" at the apolar level and in the region probed by TMA-DPH. When sunflower oil was supplemented with cod liver oil, oleic and alpha linoleic acids were increased while the 'fluidity' of the apolar core of SPM was decreased. So, the small changes in fatty acid pattern seem able to modulate neural properties i.e. the responses to a neurotoxic like ethanol. A structurally specific role of PUFA is demonstrated by the pernicious effects of the alpha linolenic acid deficient diet which are not totally prevented by the supply of long chain (n-3) PUFA. PMID- 1742322 TI - A NeuGc-containing trisialoganglioside of bovine brain. AB - A N-glycolyneuraminic acid containing trisialoganglioside was isolated from bovine brains ganglioside mixture using Q-Sepharose. Its chemical structure was characterized as IV3NeuAc, II3NeuAc-NeuGc, Gg4Cer by gas-liquid chromatography, a permethylation study, sialidase degradation, TLC/enzyme-immunostaining, fast atom bombardment-mass spectrometry, fluorometric HPLC and proton nuclear magnetic resonance spectroscopy. This was unique in the mixed sialic acid constituents. (formula; see text) This accounted for 0.78% of the gangliosides. The ceramide structure was almost identical with those of major bovine brain ganglioside, as mainly composed of 18:0 fatty acid (90.9%) and d20:0 sphingosine base. PMID- 1742323 TI - Phosphorylation of lysophosphatidylinositol by carrot membranes. AB - sn-1 Palmitoyl lysophosphatidylinositol is found in carrot suspension culture cells and can be phosphorylated to [32P]lysophosphatidylinositol monophosphate (LPIP) when [gamma 32P]ATP is added to isolated membranes. Based on in vivo labeling studies, [3H]inositol sn-1 palmitoyl LPIP was found predominantly in the plasma membrane-rich fraction or upper phase isolated by aqueous two-phase partitioning and LPI was found in the intracellular membrane-rich fraction or lower phase (Wheeler and Boss, Plant Physiol. 85, 389-392, 1987). While both membrane fractions phosphorylated LPI in vitro, the apparent Km for LPI in the intracellular membrane fraction was 180 microM and for the plasma membrane was 580 microM. When cells were treated with the ionophore, monensin, the percentage of [3H]inositol LPIP increased in the whole cell lipid extract. However, the monensin treatment decreased the amount of [3H]inositol LPIP and PIP recovered in the plasma membrane fraction relative to the sum of the individual lipid, [3H]inositol LPIP or PIP, respectively, recovered in both membrane fractions. PMID- 1742324 TI - Formation of ketols from linolenic acid 13-hydroperoxide via allene oxide. Evidence for two distinct mechanisms of allene oxide hydrolysis. AB - Incubations of [1-14C]13-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid (13 HPOT) with hydroperoxide dehydrase preparations from flax seeds lead to the formation of a novel ketol 2 along with the previously known 12-oxo-13-hydroxy 9(Z),15(Z)-octadecadienoic (12,13-alpha-ketol) and 9-hydroxy-12-oxo-10(E),15(Z) octadecadienoic (gamma-ketol) acids. Compound 2 was identified as 11-hydroxy-12 oxo-9(Z),15(Z)-octadecadienoic acid (11,12-alpha-ketol) in accordance with the data of ultraviolet, mass (chemical ionization and electron impact) and 1H-NMR spectra. During long-term (30 min) incubations the yields of gamma-ketol and 11,12-alpha-ketol increased markedly and the yield of 12,13-alpha-ketol decreased in response to the pH change from basic (pH 7.4) to acidic (pH 5.8) conditions. Short-term (15 s) incubations of 13-HPOT with hydroperoxide dehydrase, terminated by HCl fixation, led to the formation of gamma-ketol and ketol 2. A similar incubation, followed by NaOH fixation, afforded only 12,13-alpha-ketol. The trapping of allene oxide (a primary product of hydroperoxide dehydrase) with pure methanol gives only compound 4 (12,13-alpha-ketol methyl ether). Products 5 (gamma-ketol methyl ether) and 6 (11,12-alpha-ketol methyl ether) were formed along with 4 as a result of trapping with acidified methanol. The results obtained indicate that: (a) the formation of 12,13-alpha-ketol is base-dependent; (b) the formation of gamma-ketol and ketol 2 is acid-dependent. Two distinct mechanisms of allene oxide hydrolysis are proposed: (1) nucleophilic (SN2 or SN1, OH- is an attacking group) substitution, resulting in formation of 12,13-alpha ketol; (2) electrophilic (SE-like) reaction initiated by protonation of oxirane, affording gamma-ketol and 11,12-alpha-ketol. PMID- 1742325 TI - Apo B metabolism in the cynomolgus monkey: evidence for post-transcriptional regulation. AB - Previous studies have shown that hepatic apo B mRNA levels do not increase in animals fed high cholesterol diets, even though plasma apo B concentrations increase markedly. As a result, it has been suggested that the diet-induced increase in plasma apo B levels was due solely to an inhibited clearance of those lipoproteins. The present study was undertaken to test that hypothesis. Hepatic apo B mRNA levels were measured in liver biopsies taken from five male cynomolgus monkeys before and twice after, they began to consume a high cholesterol diet. The diet had no effect on hepatic apo B mRNA levels, even though it caused a 7 fold increase in the plasma apo B levels. However, measurements of the apo B secretion rate in eight separate monkeys (four chow-fed and four cholesterol-fed) by isotope dilution showed that apo B secretion by the liver was increased 4-fold in the cholesterol-fed monkeys. These data, taken together, indicate that apo B secretion is not regulated by the rate at which the apo B gene is transcribed, but at some point further along in the secretion pathway. PMID- 1742326 TI - Changes in fatty acid composition during cell differentiation in the small intestine of suckling piglets. AB - Alterations of phospholipid fatty acid composition in the renewing intestine were studied in the infant piglet. Newborn piglets were fed from birth to 2 weeks of age a concentrated cow's milk which defined a standard supply of dietary fatty acids. Phospholipids were isolated from the whole mucosa, isolated intestinal cells and purified brush border membranes. Intestinal cells were isolated according to their position along the crypt-villus axis and cell phospholipids were extracted at each step of differentiation. Changes in fatty acid composition of cell phospholipids were related to those of lactase activity in the corresponding cell homogenates. In cell phospholipids, the relative content of linoleic and linoleic acids increased about 2-fold from crypt base to villus tip. Substantial contents of alkenylacyl glycerophospholipids (plasmalogens) were found in crypt cell phospholipids and in purified brush border membrane phosphatidylethanolamine (11 and 14% of alkenyl groups by weight of total fatty acids, respectively). The proportion of alkenylacyl glycerophospholipids decreased as cells ascended the villus column and became more differentiated. The results show that fatty acid compositional changes in differentiating cell phospholipids occurred in the immature intestine (before weaning) and suggest that these alterations might be related to the appearance of specific functions. PMID- 1742327 TI - Elongation and desaturation of arachidonic and eicosapentaenoic acids in rat liver. Effect of clofibrate feeding. AB - The fatty acid elongation-desaturation ability of 5,8,11,14-eicosatetraenoic (20:4(n-6)) and 5,8,11,14,17-eicosapentaenoic (20:5(n-3)) acids was determined in both liver microsomal and light mitochondrial (rich in peroxisomes) fractions of untreated and clofibrate treated rats. The elongation and the subsequent desaturation steps were performed in the corresponding favorable media. 20:5(n-3) elongation was about 2-times more extensive than that of 20:4(n-6). Clofibrate feeding for 10 days resulted in a marked decrease in the elongation rate with the two substrates, while the delta 4 desaturation rate was increased. There were small differences in the elongation rate between the microsomal and light mitochondrial fractions, however, the relative delta 4 desaturation rate was higher in the light mitochondrial fraction than microsomes. PMID- 1742328 TI - The regulation of hepatic lipase and cholesteryl ester transfer protein activity in the cholesterol fed rabbit. AB - Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) activities are both increased in the rabbit by cholesterol feeding. The in vivo regulation of HL and CETP were explored by examining changes in specific steady-state mRNA levels upon cholesterol feeding. On feeding rabbits cholesterol, HL activity increased 3 fold after 2 days and remained at 2.6-times the control value at 28 days. Specific rabbit HL mRNA levels were assessed by dot blot analysis of liver poly (A)+ RNA hybridized with the human HL cDNA. No significant changes in liver HL mRNA accompanied the increase in activity seen at days 2 and 7. At day 28 a modest rise of 46% was observed. A significant rise in CETP activity, evident 7 days after the commencement of cholesterol feeding, was maintained until day 28 when it was 2.4-times the control value. Using the human CETP cDNA as probe, rabbit liver CETP mRNA was also found to increase by day 7, rising to 3.7-times control by day 28. The strong temporal relationship between the rise in CETP activity and mRNA (r = 0.55, P = 0.02) suggests that the regulation of CETP may be primarily effected by the levels of specific mRNA. In contrast, the discordance between levels of lipase activity and mRNA suggests that post transcriptional events may be more important in the regulation of HL in the cholesterol fed rabbit. PMID- 1742329 TI - Regulation of renin secretion by calcium and chemiosmotic forces: (patho) physiological considerations. PMID- 1742330 TI - Accumulation and excretion of long-chain acylcarnitine by rat hearts; studies with aminocarnitine. AB - During Langendorff perfusion of rat heart with aminocarnitine, long-chain acylcarnitine (LCAC) accumulates in heart cells, from which it is excreted by the heart. The heart function remains intact during this process. The accumulation of LCAC can be inhibited by the simultaneous addition of an inhibitor of the outer membrane carnitine palmitoyl-coenzyme A transferase (CPT-1), indicating that aminocarnitine is a specific inhibitor of the inner membrane isoenzyme (CPT-2). LCAC accumulation is associated with glycogen depletion. After 60 min perfusion with aminocarnitine, electron microscopy shows large multilamellar lipid vesicles, especially in cardiomyocytes, which are depleted in glycogen granula. Multilamellar lipid vesicles are also found in the blood vessels. Extraction of the perfusate shows the presence of LCAC, fatty acid and phosphatidylethanolamine. Morphological analysis with freeze fracturing and thin sectioning furthermore reveals that the sarcolemma is not deteriorated during the export of LCAC to the coronary vessels. Since cardiac structures and functions are intact, LCAC alone is not the clue for ischemic damage. Therefore the present work supports the hypothesis that acidosis rather than LCAC is of primary importance to ischemic damage. PMID- 1742331 TI - Effect of TPA on fructose 2,6-bisphosphate levels and protein kinase C activity in B-chronic lymphocytic leukemia (B-CLL). AB - Normal B lymphocytes and peripheral mononuclear blood cells from B-chronic lymphocytic leukemia (B-CLL) patients were incubated in the presence of the tumor promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In normal B lymphocytes and lymphocytes from five patients with B-CLL, TPA stimulation increased lymphocyte fructose 2,6-bisphosphate (fructose 2,6-P2) content and activity of 6-phosphofructo 2-kinase (PFK-2), which is the enzyme that catalyzes the synthesis of fructose 2,6-P2. This effect was evident after 6 h and maximal after 12-24 h of TPA exposure. In three patients, lymphocytes seemed to be refractory to TPA stimulation in the conditions described here. Lymphocyte stimulation by TPA was associated with the translocation of protein kinase C (PKC) from the soluble to the particulate membrane fraction, except in B-CLL lymphocytes refractory to the TPA effect. These results give further support to the existence within B-CLL of subsets of cells which are refractory to the stimulation by TPA and demonstrate that the tumor promoter TPA induces important metabolic changes in lymphocytes of some patients with B-CLL. PMID- 1742332 TI - Characterization of chloride transport pathways in cultured human keratinocytes. AB - In human keratinocytes, mediated transport of Cl- was found to occur mainly by two mechanisms: an anion exchange and an electrically conductive pathway. The contribution of the anion exchange, which accounted for about 50% of overall Cl- efflux, was assessed either by its sensitivity to inhibition by 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and by means of Cl- substitution experiments. The anion exchange exhibited a saturation behaviour over the range 10-135 mM Cl-; Cl- was more efficient than HCO3-, Br- and NO3- in increasing Cl- efflux rate, whereas SO4(2-) and I- inhibited Cl- efflux. The electrically conductive Cl- pathway, which accounted for about 40% of total Cl- efflux, was inhibited by the Cl- channel blocker 5-nitro-2-(3 phenylpropylamino)benzoic acid (NPPB) and was at least partially sensitive to variation of the plasma membrane potential. The Cl- channel was insensitive to elevation in the intracellular concentration of either cyclic AMP and calcium ions. Indomethacin, an inhibitor of the cyclooxygenase, failed to reduce Cl- efflux, whereas nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase, induced 50% inhibition of Cl- efflux. These results support the conclusion that endogenous production of lipoxygenase-derived arachidonic acid metabolite(s) might be responsible for high basal Cl- permeability in human keratinocytes. PMID- 1742333 TI - Modulation of synovial fibroblast plasminogen activator and plasminogen activator inhibitor production by protein kinase C. AB - Phorbol myristate acetate (PMA) added to human synovial fibroblast cultures caused a dose-dependent increase in the production of plasminogen activator inhibitor-type 1 (PAI-1). In addition, PMA inhibited endogenous and interleukin-1 (IL-1) induced plasminogen activator (PA) activity, while increasing mRNA PAI-1 levels. Other protein kinase C (PKC) activators, mezerein and teleocidin B4, caused similar effects. The simultaneous addition of the PKC antagonists, H-7 or staurosporine, prevented the inhibition of PA activity by PMA. This study shows that activation of PKC inhibits PA and stimulates PAI production in human synovial fibroblasts. These results suggest that activation of PKC may play an important role in regulating increased PA production associated with joint destruction in rheumatoid arthritis (RA). PMID- 1742334 TI - Altered blood amino acid distribution in genetically obese mice. AB - The present study was undertaken to determine whether the alteration in amino acid distribution between the plasma and cellular compartment of the blood, previously described in dietary-obese rats, also occurs in genetically obese mice. The blood concentration of individual amino acids and its distribution between plasma and cells of lean and genetically obese mice (ob/ob) have been measured. The results demonstrated that genetically obese mice showed a decrease (55%, P = 0.0489) of free amino acids in the blood cells. Most amino acids were affected and among the most noteworthy characteristics was the observation that the reduction in concentration was more pronounced for the total concentration of the essential amino acids which was reduced by 76% (P = 0.0112) compared to cells of lean mice. These results suggest that an altered amino acid distribution between plasma and blood cells is a consequence of both diet-induced and genetic obesities. PMID- 1742335 TI - Purification and properties of the uracil DNA glycosylase from Bloom's syndrome. AB - Bloom's syndrome uracil DNA glycosylase was highly purified from two non transformed cell strains derived from individuals from different ethnic groups. Their properties were then compared to two different highly purified normal human uracil DNA glycosylases. A molecular mass of 37 kDa was observed for each of the four human enzymes as defined by gel-filtration column chromatography and by SDS PAGE. Each of the 37 kDa proteins was identified as a uracil DNA glycosylase by electroelution from the SDS polyacrylamide gel, determination of glycosylase activity by in vitro biochemical assay and identification of the reaction product as free uracil by co-chromatography with authentic uracil. Bloom's syndrome enzymes differed substantially in their isoelectric point and were thermolabile as compared to the normal human enzymes. Bloom's syndrome enzymes displayed a different Km, Vmax and were strikingly insensitive to 5-fluorouracil and 5 bromouracil, pyrimidine analogues which drastically decreased the activity of the normal human enzymes. In particular, each Bloom's syndrome enzyme required 10-100 fold higher concentrations of each analogue to achieve comparable inhibition of enzyme activity. Potential mechanisms are considered through which an altered uracil DNA glycosylase characterizing this cancer-prone human genetic disorder may arise. PMID- 1742336 TI - Immunochemical comparison of the major intrinsic protein of eye-lens fibre cell membranes in mice with hereditary cataracts. AB - Expression of the major intrinsic protein (MIP) of eye-lens fibre cell membranes was compared in normal (DBA), cataractous (CAT, LOP, NCT) and chimaeric (CBA-LOP) mice at different stages of development using immunofluorescence microscopy and immunoblotting techniques. MIP of apparent molecular mass 26 kDa was detected in extracts of adult DBA, LOP and CBA-LOP lenses, but only low molecular mass (less than 26 kDa) immunoreactive proteins were detected in similar extracts from adult CAT and NCT lenses. The corresponding MIP distribution patterns confirmed the highly organised fibre-cell histology in embryonic DBA and adult CBA-LOP lenses and also highlighted the severe fibre-cell degeneration in the LOP lens. In contrast, however, no immunoreactive MIP was detected in situ in embryonic CAT and NCT lenses. These results suggest that a structural alteration of MIP occurs during embryonic lens development in the cataractous CAT (dominant) and NCT (recessive) mutant mice. PMID- 1742337 TI - Prepartal lactose concentration in the mammary glands of Uje: WIST rats as a simple indicator of approaching parturition. AB - Immediately after delivery, lactose was reliably detectable in rat mammary glands (mean concentration 6.49 +/- 0.57 mg/g tissue). The concentrations were not influenced by prepartal biopsy of contralateral mammary tissue. In the morning of the 21st day of gestation (= expected day of labor), lactose was evident in the mammary glands of dams delivering at that day (mean concentration 2.39 +/- 0.17 mg/g tissue). In the tissue of dams delivering on day 22 of gestation, lactose was undetectable. A correlation between prepartal lactose concentration of mammary gland and time remaining up to beginning of delivery (r = -0.96) qualifies this parameter as a rough indicator of term of parturition. PMID- 1742338 TI - Group formation of previously single-caged adult rhesus macaques for the purpose of environmental enrichment. AB - An attempt was made to form two groups of 6 previously single-caged adult female and 6 previously single-caged adult male rhesus macaques. The study was based on the premise that simultaneous introduction of familiar animals reduces the risks involved during group formation. Future group members were therefore given ample opportunity to physically interact with each other on a one-to-one basis and were considered ready for group formation only when they had demonstrated compatibility and clear-cut dominance-subordination relationships. Both group formation attempts were failures. Aggressive incompatibility was heralded by certain subjects challenging other partners to whom they had originally been subordinate. Aggressive harassment was intensive and persistent. Victims showed no resistance except for fear-grinning and crouching in submission. They did so to no avail. Both groups were split again within the first hour of introduction to avoid fatal consequences. It was concluded, that unlike pair-housing, group housing of previously single caged adult rhesus macaques is associated with considerable risks which cannot be overcome by systematically familiarizing all group members before the animals are introduced as a group. There is no guarantee that well established dyadic relationships do not break down within the more complex social structure of the group, thereby triggering aggressive conflicts that put the animals' safety into undue jeopardy. PMID- 1742339 TI - Immune response of the Mongolian gerbil (Meriones unguiculatus) to sheep red blood cells. AB - The immune responses of Mongolian gerbils, Meriones unguiculatus, to sheep red blood cells (SRBC) were studied as compared to those of mice. After a single injection of SRBC, hemagglutinin titers in gerbils were significantly lower and hemolytic plaque-forming cells (PFC) in the spleen were less in number as compared to the response of mice. In gerbils the PFC response to a higher dose of bacterial lipopolysaccharide (LPS) was rather higher than in mice. The delayed type hypersensitivity (DTH) assay on the foot-pad revealed that the responsiveness was considerably lower in gerbils than in mice. PMID- 1742340 TI - Influence of chronic stress before and/or during gestation on pregnancy outcome of young and old Uje: WIST rats. AB - Young (70-120 d) and old (11-13 month) Uje:WIST rats were exposed to the strong stressor "chronic restraint" before and/or during gestation. Most adverse effects on pregnancy outcome were induced in young dams stressed before and during gestation (prolonged duration of pregnancy, lower body mass of the newborn pups). In old dams chronic restraint did not further deteriorate the age-dependent poor reproductive performance, but even rejuvenated it, if stress exposure was limited to the premating period. PMID- 1742341 TI - The effect of transportation stress on circulating corticosteroids, enzyme activities and hematological values in laboratory dogs. AB - Stress during transportation was monitored in truck-transported Beagle dogs "IVTK HD". Cortisol (F), corticosterone (B), red and white blood cell parameters, and enzyme activities in plasma were estimated. Plasma levels of cortisol and corticosterone were increased significantly during transportation and returned to basal values overnight post arrival. Hematocrit, hemoglobin, erythrocytes and leukocytes increased moderately. No obvious differences in enzyme activities were observed. Only alpha-HBDH values dropped significantly at the end of the 9.5 h transport period. This study confirms, although individual reaction is remarkably different, transportation as a potent stressor for Beagle dogs. PMID- 1742342 TI - Basic fibroblast growth factor requires a long-lasting activation of protein kinase C to induce cell proliferation in transformed fetal bovine aortic endothelial cells. AB - Basic fibroblast growth factor (bFGF) induces a protein kinase C (PKC)-dependent mitogenic response in transformed fetal bovine aortic endothelial GM 7373 cells. A long-lasting interaction of bFGF with the cell is required to induce cell proliferation. bFGF-treated cells are in fact committed to proliferate only after they have entered the phase S of the cell cycle, 12-14 h after the beginning of bFGF treatment. Before that time, the mitogenic response to bFGF is abolished by 1) removal of extracellular bFGF by suramin, 2) addition of neutralizing anti bFGF antibodies to the culture medium, 3) inhibition of PKC activity by the protein kinase inhibitor H-7, and 4) down-regulation of PKC by cotreatment with phorbol ester. Thus the requirement for a prolonged interaction of bFGF with the cell reflects the requirement for a prolonged activation of PKC. Similar conclusions can be drawn for the PKC activators 12-O-tetradecanoyl phorbol 13 acetate and 1,2-dioctanoyl-sn-glycerol. The two molecules require 16 and 6 h, respectively, of activation of PKC to induce 50% of maximal cell proliferation. The requirement for a long-lasting activation of PKC appears to be a mechanism for the control of cell proliferation capable of discriminating among transient nonmitogenic stimuli and long-lasting mitogenic stimuli. PMID- 1742343 TI - Regulation of Cl/HCO3 exchange in gastric parietal cells. AB - Microspectrofluorimetry of the fluorescent indicators 2',7'-bis-(2-carboxyethyl) 5(and-6)carboxyfluorescein and 6-methoxy-N-(3-sulfopropyl)-quinolinium was used to measure intracellular pH (pHi), intracellular Cl (Cli), and transmembrane fluxes of HCO3 and Cl in single parietal cells (PC) in isolated rabbit gastric glands incubated in HCO3/CO2-buffered solutions. Steady-state pHi was 7.2 in both resting (50 microM cimetidine) and stimulated (100 microM histamine) PCs. Transmembrane anion (HCO3 or Cl) flux rates during Cl removal from or readdition to the perfusate were the same in resting and stimulated PCs. These rates increased at alkaline pHi, though this pHi dependence was small in the physiological range. Maximum velocity (Vmax) for Cl influx or HCO3 efflux was 80 110 mM/min at pHi 7.6-7.8, and the Km for extracellular concentrations of Cl (Clo) was 25 mM; in the physiological range (pHi 7.1-7.3), Vmax for anion fluxes was approximately 50 mM/min. Steady-state Cli in the unstimulated PC was 62 +/- 5 mM, but on histamine stimulation, Cli decreased rapidly to 25 mM and then increased back to a steady-state level of 44 mM. HCO3 fluxes due to Cl removal or readdition were completely blocked by 0.5 mM 4,4'-diisothiocyanatodihydrostilbene 2,2'-disulfonic acid (H2DIDS), but Cl fluxes were only inhibited by 80%. H2DIDS did not inhibit the decrease in Cli that occurred with histamine treatment. Diphenylamine carboxylate (0.5 mM) inhibited Cl flux by only 50% and caused no additional inhibition of Cl flux when used in conjunction with H2DIDS. Transmembrane anion fluxes during solution Cl removal or readdition occurred 80% through the anion exchanger at the basal membrane and 20% through other pathway(s), presumably the Cl channel in the apical membrane. We conclude that the increase in transport activity via the Cl/HCO3 exchanger that occurs during histamine-induced increases in HCl secretion is due mostly to the decrease in Cli. In the resting cell with Cli = 62 mM, Clo = 120 mM, pHi = 7.2, and extracellular pH = 7.4, the anion exchanger is poised near its thermodynamic equilibrium. During histamine stimulation Cli drops from 62 mM to 44 mM, the thermodynamic equilibrium of the anion exchanger at the basolateral membrane is disturbed, and the anion exchanger then exchanges cellular HCO3 for extracellular Cl. Cli serves a crucial regulatory role in stimulus-secretion coupling in the PC. PMID- 1742345 TI - Site-directed mutagenesis and NMR spectroscopic approaches to the elucidation of the structure-function relationships in translation initiation factors IF1 and IF3. PMID- 1742344 TI - Wound-factor-induced and cell cycle phase-dependent expression of 9E3/CEF4, the avian gro gene. AB - The gro genes encode for secreted proteins with sequence homologies to inflammatory mediators. Little is known about the function of these proteins or their regulation. The chicken gro (9E3/CEF4) is expressed abundantly in the cells of proliferating cultures but at very low levels in confluent cultures. In vivo, this gene is expressed in connective tissue and overexpressed at sites of injury, especially in areas of neovascularization. Here we provide a bridge between these observations by examining in culture the effect on 9E3 expression and DNA synthesis induced by cell damage and by addition of factors known to be released on wounding. We mimicked wounding by scraping swaths across confluent cultures of embryonic fibroblasts and determined the time dependence of expression of 9E3 mRNA and incorporation of 3H-thymidine. We find that 9E3 is (1) transiently expressed after "wounding" or serum-stimulation; (2) expressed in a cell cycle phase-dependent manner; it is triggered during the G0-G1 transition or early in G1 and subsides during S-phase; and (3) stimulated to high levels by a-fibroblast growth factor (aFGF), bFGF, transforming growth factor alpha (TGF alpha), and TGF beta, to intermediate levels by platelet-derived growth factor and not stimulated by epidermal growth factor. We also find that cells that are constantly cycling do not express 9E3, indicating that they skip either the portion of the cell cycle where 9E3 is induced or that they constitutively express a repressor of transcription or an RNA-degrading enzyme. Taken together, these observations suggest that the product of this gene could play more than one role in vivo. For example, in normal tissues the 9E3 protein could be involved in the exit of cells from the resting stage, whereas during wound healing the secreted protein or its cleavage products also could play a role in angiogenesis. PMID- 1742346 TI - Eukaryotic initiation factors eIF-2 and eIF-3: interactions, structure and localization in ribosomal initiation complexes. AB - More than ten different protein factors are involved in initiation of protein synthesis in eukaryotes. For binding of initiator tRNA and mRNA to the 40S ribosomal subunit, the initiation factors eIF-2 and eIF-3 are particularly important. They consist of several different subunits and form stable complexes with the 40S ribosomal subunit. The location of eIF-2 and eIF-3 in these complexes as well as the interactions of the individual components have been analyzed by biochemical methods and electron microscopy. The results obtained are summarized in this article, and a model is derived describing the spatial arrangement of eIF-2 and eIF-3 together with initiator tRNA and mRNA on the 40S subunit. Conclusions on the location of functionally important sites of eukaryotic small ribosomal subunits are discussed with regard to the respective location of these sites in the prokaryotic counterpart. PMID- 1742347 TI - 2'-O-methylation and inosine formation in the wobble position of anticodon substituted tRNA-Phe in a homologous yeast in vitro system. AB - Four variants of yeast tRNA-Phe in which the anticodon and 3'-adjacent nucleotide (GmAAY) have been replaced by synthetic tetranucleotides NAAG (where N is each of the four canonical nucleosides G, C, U or A) are substrates for a yeast tRNA modification enzyme which catalyses the S-adenosyl-L-methionine dependent formations of Gm-34, Cm-34, Um-34, Am-34 and Im-34 (where Nm represents a 2'-O methylnucleoside and I inosine). The kinetics of these nucleosides-34 2'-O methylations reveal that yeast tRNA-Phe with G-34 (the natural substrate) is less efficiently modified than variants of the same tRNA containing U-34 and C-34. The formation of Am-34 in the tRNA containing A-34 was found to be particularly inefficient. However, in this tRNA, we observed the formation of I-34 followed by a 2'-O-methylation (giving rise to Im-34). In the yeast in vitro system described here, inosine formation is not dependent on the addition of any cofactor including hypoxanthine; the mechanism of inosine formation in yeast tRNA might therefore be distinct from that found in higher eukaryotes. PMID- 1742348 TI - Overproduction of the Thermus thermophilus elongation factor Tu in Escherichia coli. AB - The elongation factor Tu (EF-Tu) encoded by the tufl gene of the extreme thermophilic bacterium Thermus thermophilus HB8 was expressed under control of the tac promoter from the recombinant plasmid pEFTu-10 in Escherichia coli. Thermophilic EF-Tu-GDP, which amounts to as much as 35% of the cellular protein content, was separated from the E coli EF-Tu-GDP by thermal denaturation at 60 degrees C. The overproduced E coli-born T thermophilus EF-Tu was characterized by: i) recognition through T thermophilus anti-EF-Tu antibodies; ii) analysis of the peptides obtained by cyanogen bromide cleavage; iii) thermostability; iv) guanine nucleotide binding activity in the absence and the presence of elongation factor Ts; and v) ternary complex formation with phenylalanyl-tRNAPhe and GTP. PMID- 1742349 TI - How many EF-Tu molecules participate in aminoacyl-tRNA binding? AB - The stoichiometry of the EF-Tu-GTP-aminoacyl-tRNA complex has been re-determined by a variety of methods, viz gel filtrations, fluorescence titrations, as well as hydrolysis and RNase protection experiments. The results of these experiments clearly demonstrate that one aminoacyl-tRNA interacts with only one EF-Tu-GTP molecule, in agreement with the established view and in contrast to the recently published results by Ehrenberg et al [6]. PMID- 1742350 TI - Structure-function relationships of elongation factor Tu as studied by mutagenesis. AB - We have modified elongation factor Tu (EF-Tu) from Escherichia coli via mutagenesis of its encoding tufA gene to study its function-structure relationships. The isolation of the N-terminal half molecule of EF-Tu (G domain) has facilitated the analysis of the basic EF-Tu activities, since the G domain binds the substrate GTP/GDP, catalyzes the GTP hydrolysis and is not exposed to the allosteric constraints of the intact molecule. So far, the best studied region has been the guanine nucleotide-binding pocket defined by the consensus elements typical for the GTP-binding proteins. In this area most substitutions were carried out in the G domain and were found to influence GTP hydrolysis. In particular, the mutation VG20 (in both G domain and EF-Tu) decreases this activity and enhances the GDP to GTP exchange; PT82 induces autophosphorylation of Thr82 and HG84 strongly affects the GTPase without altering the interaction with the substrate. SD173, a residue interacting with (O)6 of the guanine, abolishes the GTP and GDP binding activity. Substitution of residues Gln114 and Glu117, located in the proximity of the GTP binding pocket, influences respectively the GTPase and the stability of the G domain, whereas the double replacement VD88/LK121, located on alpha-helices bordering the GTP-binding pocket, moderately reduces the stability of the G domain without greatly affecting GTPase and interaction with GTP(GDP). Concerning the effect of ligands, EF-TuVG20 supports a lower poly(Phe) synthesis but is more accurate than wild type EF-Tu, probably due to a longer pausing on the ribosome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742351 TI - The function of the translating ribosome: allosteric three-site model of elongation. AB - During the last decade, a new model for the ribosomal elongation cycle has emerged. It is based on the finding that eubacterial ribosomes possess 3 tRNA binding sites. More recently, this has been confirmed for archaebacterial and eukaryotic ribosomes as well, and thus appears to be a universal feature of the protein synthetic machinery. Ribosomes from organisms of all 3 kingdoms harbor, in addition to the classical P and A sites, an E site (E for exit), into which deacylated tRNA is displaced during translocation, and from which it is expelled by the binding of an aminoacyl-tRNA to the A site at the beginning of the subsequent elongation round. The main features of the allosteric 3-site model of ribosomal elongation are the following: first, the third tRNA binding site is located 'upstream' adjacent to the P site with respect to the messenger, ie on the 5'-side of the P site. Second, during translocation, deacylated tRNA does not leave the ribosome from the P site, but co-translocates from the P site to the E site--when peptidyl-tRNA translocates from the A site to the P site. Third, deacylated tRNA is tightly bound to the E site in the post-translocational state, where it undergoes codon--anticodon interaction. Fourth, the elongating ribosome oscillates between 2 main conformations: (i), the pre-translocational conformer, where aminoacyl-tRNA (or peptidyl-tRNA) and peptidyl-tRNA (or deacylated tRNA) are firmly bound to the A and P sites, respectively; and (ii), the post translocational conformer, where peptidyl-tRNA and deacylated tRNA are firmly bound to the P and E sites, respectively. The transition between the 2 states is regulated in an allosteric manner via negative cooperatively. It is modulated in a symmetrical fashion by the 2 elongation factors Tu and G. An elongating ribosome always maintains 2 high-affinity tRNA binding sites with 2 adjacent codon--anticodon interactions. The allosteric transition from the post- to the pre-translocational state is involved in the accuracy of aminoacyl-tRNA selection, and the maintenance of 2 codon--anticodon interactions helps to keep the messenger in frame during translation. PMID- 1742352 TI - The influence of tRNA located at the P-site on the turnover of EF-Tu.GTP on ribosomes. AB - The turnover of EF-Tu.GTP on poly-U programmed ribosomes was measured both in the presence and in the absence of N-acetylated Phe-tRNA(Phe) at the P-site. The reaction was uncoupled from protein synthesis by omitting Phe-tRNA(Phe) at the A site. In this reaction, the ribosome can be considered as an enzyme catalysing the transition of EF-Tu.GTP to EF-Tu.GTP. A constant EF-Tu.GTP concentration is maintained by regenerating GDP to GTP at the expense of phosphoenolpyruvate by pyruvate kinase. The rate constants are determined using a procedure which corrects for the reduction in specific activity of GTP due to regeneration of the nucleotide. Ribosomes with an occupied P-site are more efficient in stimulating the GTPase of EF-Tu.GTP than ribosomes with an empty P-site. The data suggest that this is mainly caused by an increased affinity of EF-Tu.GTP for ribosomes with a filled P-site rather than by an enhanced reactivity of the GTPase centre. PMID- 1742353 TI - Functional aspects of ribosomal proteins. AB - A short personal recollection of HG Wittmann is given with emphasis on his basic contribution to the structure of the ribosome, in particular the ribosomal proteins. With these considerations in mind, two interrelated problems are reviewed here. The first relates to the internal symmetry both in tRNA and in the tetrameric L12-protein complex. The second problem to be addressed relates to the dynamics of transfer RNA in the ribosome and the role of L12 proteins in this process. The importance of electrostatic repulsion in the maintenance of the mutual spatial orientation of tRNAs and L12 in the ribosome is emphasized in relation to a pendulum model for how L12 may steer translocation. PMID- 1742354 TI - The use of synthetic tRNAs as probes for examining nascent peptides on Escherichia coli ribosomes. AB - The polyuridylic acid-dependent syntheses of polycysteine and polyserine were carried out on Escherichia coli ribosomes using two new synthetic tRNA species. The peptides were initiated with N-acetyl or N-acyl coumarin derivatives of either Ser-tRNA or Phe-tRNA. The properties of the resulting nascent peptides were compared to those of nascent polyphenylalanine chains synthesized under similar conditions. This was accomplished by following changes in the fluorescence properties of the probes covalently linked to the amino-terminus of each of the nascent polypeptides as they were formed on the ribosomes. Nascent polycysteine and polyserine peptides appeared quite different from those of polyphenylalanine, as indicated by the anisotropy of fluorescence from the amino terminal probe. In contrast to serine and cysteine peptides, the synthesis of all the polyphenylalanine peptides was insensitive to inhibition by erythromycin, even though these peptides were initiated with N-acyl serine. The results support the hypothesis that nascent polyphenylalanine peptides have atypical physical and chemical properties and demonstrate the utility of using modified tRNAs to study ribosome function and the synthesis of proteins. PMID- 1742355 TI - Interaction of the release factors with the Escherichia coli ribosome: structurally and functionally-important domains. AB - There are two major domains of interaction between the Escherichia coli release factors (RF-1 and RF-2) and each subunit of the ribosome. RF-2 has a binding domain on the shoulder and lower head region of the small subunit at the small lobe distant from the decoding site. This is in close proximity to one of the domains on the large subunit which includes the body dimer of L7/L12 and L11. The other domains of interaction, at the decoding site on the small subunit, and at the peptidyltransferase centre of the large subunit of the ribosome, are some distance from the first two, although the evidence for direct contact with the ribosome is less comprehensive. The release factors may therefore have two distinct structural domains, and in support of this concept RF-1 and RF-2 can both be cleaved into two fragments by papain. Region-specific antibodies, and antibodies against defined peptide within the RF sequences have given an indication that a significant part of an interacting RF molecule is in close proximity to the ribosome surface, confirming an observation by immunoelectron microscopy which suggested that the RF penetrates deeply into the cleft between the two subunits. A region of highly conserved primary sequence between the two release factors from E coli is also conserved in those from B subtilis suggesting it forms an important structural or functional domain. Antibodies against peptides from the N-terminal end of this region strongly inhibit binding of the RF to the ribosome. PMID- 1742356 TI - A rRNA-mRNA base pairing model for UGA-dependent termination. AB - A series of site-directed mutations has been constructed in E coli 16S rRNA and shown to suppress UGA-dependent translational termination. With the exception of the C726 to G base change, all were constructed in helix 34. Characterization of these mutations is reviewed here and from these data and mRNA-rRNA base pairing model for the termination event is presented. The interaction functions via antiparallel base pairing between either 1 of the 2 UCA motifs in helix 34 and the complementary UGA stop codon on the message, thus forming a quasicontinuous A type helical structure that is further stabilized by stacking enthalpy. Finally, rRNA motifs potentially required for UAA and UAG-dependent translational termination are discussed. PMID- 1742357 TI - Effect of ADP-ribosylation and phosphorylation on the interaction of elongation factor 2 with guanylic nucleotides. AB - Samples of unmodified EF-2, EF-2 ADP-ribosylated with diphtheria toxin and NAD, and/or phosphorylated using ATP and the Ca(2+)-calmodulin dependent kinase III partially purified, were irradiated at 254 nm with 32P-labeled GDP or GTP, and analyzed by one- and two-dimensional gel electrophoresis. By this method we showed that unmodified EF-2 formed a stable complex with GDP but not with GTP, whereas phosphorylated EF-2 and ADP-ribosylated + phosphorylated EF-2 formed stable complexes even in the absence of irradiation, with GTP but not GDP. ADP ribosylated EF-2 did not form stable complexes with either GDP or GTP. Prior ADP ribosylation of EF-2 increased its ability to the phosphorylated. These results show that the structures of the two domains containing diphtamide 715 and the phosphorylatable threonines (between Ala 51 and Arg 60) are interdependent; modifications of these residues induce different conformational changes of EF-2 which alter the interactions of the factor with guanylic nucleotides as well with ribosomes. PMID- 1742358 TI - Conserved amino acid residues in ribosome-inactivating proteins from plants. AB - The amino acid sequences of eleven RIPs sequenced to date have been compared in the expectation that this would be useful in the location of functionally and/or structurally important sites of these molecules. In addition to several highly conserved hydrophobic amino acids, thirteen absolutely conserved residues have been found in ricin A-chain: Tyr21, Phe24, Arg29, Tyr80, Tyr123, Gly140, Ala165, Glu177, Ala178, Arg180, Glu208, Asn209 and Trp211. The role of these residues as well as of the C-terminal region have been discussed based on the results of chemical and enzymatic modifications, site-directed mutagenesis, and deletion studies. PMID- 1742359 TI - Suppression of defective-sporulation phenotypes by mutations in transcription factor genes of Bacillus subtilis. AB - Mutations in the Bacillus subtilis major RNA polymerase sigma factor gene (rpoD/crsA47) and a sensory receiver gene (spoOA/rvtA11) are potent intergenic suppressors of several stage 0 sporulation mutations (spoOB, OE, OF & OK). We show here that these suppressors also rescue temperature-sensitive sporulation phenotypes (Spots) caused by mutations in RNA polymerase, ribosomal protein, and protein synthesis elongation factor EF-G genes. The effects of the crsA and rvtA suppressors on RNA polymerase and ribosomal protein spots mutations are similar to those previously described for mutations in another intergenic suppressor gene rev. We have examined the effects of rvtA and crsA mutations on the expression of sporulation-associated membrane proteins, including flagellin and penicillin binding protein 5* (PBP 5*). Both suppressors restored sporulation and synthesis of PBP 5* in several spoO mutants. However, only rvtA restored flagellin synthesis in spoO suppressed backgrounds. The membrane protein phenotypes resulting from the presence of crsA or rvtA suppressors in spoO strains suggests that these suppressors function via distinct molecular mechanisms. The rvtA and crsA mutations are also able to block the ability of ethanol to induce spoO phenocopies at concentrations of ethanol which prevent sporulation in wild type cells. The effects of ethanol on sporulation-associated membrane protein synthesis in wild type and suppressor containing strains have been examined. PMID- 1742360 TI - Characterization and primary structure of proteins L28, L33 and L34 from Bacillus stearothermophilus ribosomes. AB - The complete amino acid sequences of 3 proteins from the 50S subunit of Bacillus stearothermophilus ribosomes were determined by N-terminal sequence analysis and by sequencing of overlapping fragments obtained from enzymatic digestions and chemical cleavages. The proteins BstL28, BstL33 and BstL34, named according to the equivalent proteins in Escherichia coli ribosomes, consist of 60, 49, and 44 amino acid residues and have calculated molecular masses of 6811.0, 5908.6, and 5253.9 Da, respectively. They are highly basic with a content of positively charged residues ranging between 29% for L33 and 45% for L34. The 3 proteins were positioned in the 2-dimensional map of B stearothermophilus 50S ribosomal proteins. The electrophoretic mobilities confirm sizes and net charges deduced from the sequences. PMID- 1742361 TI - The primary structure of rat ribosomal proteins P0, P1, and P2 and a proposal for a uniform nomenclature for mammalian and yeast ribosomal proteins. AB - The covalent structures of rat ribosomal proteins P0, P1, and P2 were deduced from the sequences of nucleotides in recombinant cDNAs. P0 contains 316 amino acids and has a molecular weight of 34,178; P1 has 114 residues and a molecular weight of 11,490: and P2 has 115 amino acids and a molecular weight of 11,684. The rat P-proteins have a near identical (16 of 17 residues) sequence of amino acids at their carboxyl termini and are related to analogous proteins in other eukaryotic species. A proposal is made for a uniform nomenclature for rat and yeast ribosomal proteins. PMID- 1742362 TI - On the conformation of the alpha sarcin stem-loop of 28S rRNA. AB - A synthetic RNA that is a substrate for the cytotoxin alpha sarcin has been examined by NMR. The molecule in question includes the entire sequence of the so called alpha sarcin loop from rat 28S rRNA (U4316-C4332), and it is cleaved at the residue that corresponds to G4325, the site of alpha sarcin cleavage in 28S rRNA. The data show that the terminal stem designed into the molecule's sequence exists, as expected, and that its loop has a definite structure, which is stable to at least 40 degrees C under ionic conditions compatible with its cleavage by alpha sarcin. PMID- 1742363 TI - The interplay between X-ray crystallography, neutron diffraction, image reconstruction, organo-metallic chemistry and biochemistry in structural studies of ribosomes. AB - Crystals of ribosomes, their complexes with components of protein biosynthesis, their natural, mutated and modified subunits, have been subjected to X-ray and neutron crystallographic analyses. Electron microscopy and 3-dimensional image reconstruction, supported by biochemistry, genetic, functional and organo metallic studies were employed for facilitating phasing of the crystallographic data. For example, a monofunctional multi heavy-atom cluster (undecagold) was designed for covalent and quantitative binding to ribosomes. The modified particles were crystallized isomorphously with the native ones. Their difference Patterson maps contain indications for the usefulness of these derivatives for subsequent phasing. Models of the ribosome and its large subunit were reconstructed from tilt series of 2-dimensional sheets. The comparison of the various reconstructed images enabled an initial assessment of the reliability of these models and led to tentative assignments of several functional features. These include the presumed sites for binding mRNA and for codon-anticodon interactions, the path taken by the nascent protein chain and the mode for tRNA binding to ribosomes. These assignments assisted in the design of biologically meaningful crystal systems. The reconstructed models are being used to identify structural features in initial density maps derived from X-ray and neutron diffraction data. PMID- 1742364 TI - Heterogeneity of Escherichia coli ribosomes established by scanning transmission electron microscopy. AB - Quantitative mass image analysis of Escherichia coli ribosomal particles by scanning transmission electron microscopy (STEM) provided direct evidence that presumably homogeneous preparations of ribosomes are, in reality, populations of heterogeneous particles. Variations in composition, relative molecular mass (Mr) and shape were observed both in the monosomes and in the ribosomal subunits. None of these changes can be resolved visually; they can be evaluated only by computer processing. The variations in relative mass and shape monitored by values of radius of gyration (RG) were attributed to the loss of ribosomal proteins and/or factors and correlated with the changes in ribosome composition and biological activity. The highest activity was found in monosomes prepared from the standard 0.5 M NH4Cl wash. With increasing concentrations (up to 1.5 M) of NH4Cl in the wash buffer the activity decreased slowly, then dropped rapidly to about half in 2 M NH4Cl. The most striking effects were observed in ribosomal particles washed with 0.1 M NH4Cl. The 70S monosomes and the 30S subunits attained maximum Mr and RG values (2660 kDa and 76 A, and 990 kDa and 75 A, respectively), which were greater than the theoretical values, while the activity was minimal (approximately 12%). The Mr and RG parameters of the 50S subunits remained uneffected by the NH4Cl washes (approximately 1600 kDa and 68 A). PMID- 1742365 TI - How does the mRNA pass through the ribosome? AB - A working model of the mRNA path through the ribosome is proposed. According to the model, the template goes around the small ribosomal subunit along the region where its 'head' is separated from other parts of the subunit. The 5'-end of the mRNA fragment covered by the ribosome is located near the 3'-terminus of 16S rRNA, whereas the 3'-terminal residues of the fragment are situated on the outer surface of the subunit, opposite its 'side ledge'. When associated with the 50S subunit, the 30S subunit is oriented in such a manner that the decoding center faces the L7/L12 stalk. Implications of the proposed working model of the mRNA topography for the function of the ribosome are discussed. PMID- 1742366 TI - The side-by-side model of two tRNA molecules allowing the alpha-helical conformation of the nascent polypeptide during the ribosomal transpeptidation. AB - Lim and Spirin [25] proposed a preferable conformation of the nascent peptide during the ribosomal transpeptidation. Spirin and Lim [26] excluded the possibilities of the side-by-side model proposed by Johnson et al [13] and the three-tRNA binding model (A, P and E sites) of Rheinberger and Nierhaus [3]. However, a slight conformational change at the 3' end regions of both A and P site tRNA molecules can enable the three different tRNA binding models to converge. With a modification of the angles of the ribose rings of both anticodon and mRNA this model can also be related to the model of Sundaralingam et al [19]. In this model of E coli rRNA the 3' end sequence ACCA76 or GCCA76 of P site tRNA is base-paired to UGGU810 of 23S rRNA, while the ACC75 or GCC75 of A site tRNA are base-paired to GGU1621 23S rRNA. The conformation of the A76 of A site tRNA is necessarily different from that of P site tRNA, at least during the course of the transpeptidation. The A76 of A site tRNA overlaps the binding region of puromycin. The C1400 of 16S rRNA in this model is located at a distance of 4 A from the 5' end of the anticodon of P site tRNA [14] and 17 A from the 5' end of the anticodon of A site tRNA [15]. It is also shown that a considerable but reasonable modification in the conformation of the anticodon loops could lead to accommodation of three deacylated tRNA(Phe) molecules at a time on 70S ribosome in the presence of poly(U) as observed experimentally [6]. A sterochemical explanation for the negatively-linked allosteric interactions between the A and E sites is also shown in the present model. PMID- 1742367 TI - Superexpression and fast purification of E coli initiation factor IF2. AB - For the production of large quantities of E coli initiation factor IF2 we have constructed an improved overexpression system. The gene infB was cloned into the thermo-inducible runaway plasmid pCP40 [1] and subsequently transformed into the E coli strain C600[pcI857]. In this system the expression of infB is under the control of the strong promoter lambda PL and the cells carry the plasmid pcI857, which contains a thermosensible lambda cI repressor. Overexpression of IF2, which is approximately 30 times higher than the expression in wild-type-cells, is induced at 42 degrees C and continues for 2 h at 37 degrees C. From these cells pure and active IF2 was obtained using a novel 3-step FPLC-procedure consisting of ion-exchange liquid chromatography on Q-sepharose HP, MonoQ and MonoS. In approximately 8 h, 5 mg of pure and active IF2 can be obtained from 10 g overproducing cells. This corresponds to 5 mg of IF2 per litre of medium. The purification was monitored by Western immunoblotting and the activity of the purified factor was tested by measuring the stimulation of binding of the initiator fMet-tRNA(Met)f to 70S ribosomes in the presence of GTP and poly(A,U,G) as messenger RNA. Compared with previous methods our purification procedure avoids the use of materials such as DEAE-cellulose and phosphocellulose which have relatively poor flow rates. In addition to the higher flow capacity of Q sepharose HP, this new matrix can be loaded with an S30 supernatant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742368 TI - Unbiased measures of transmitted information and channel capacity from multivariate neuronal data. AB - Two measures from information theory, transmitted information and channel capacity, can quantify the ability of neurons to convey stimulus-dependent information. These measures are calculated using probability functions estimated from stimulus-response data. However, these estimates are biased by response quantization, noise, and small sample sizes. Improved estimators are developed in this paper that depend on both an estimate of the sample-size bias and the noise in the data. PMID- 1742369 TI - On the sufficiency of the velocity field for perception of heading. AB - All models of self-motion from optical flow assume the instantaneous velocity field as input. We tested this assumption for human observers using random-dot displays that simulated translational and circular paths of movement by manipulating the lifetime and displacement of individual dots. For translational movement, observers were equally accurate in judging direction of heading from a "velocity field" with a two-frame dot life and a "direction field" in which the magnitudes of displacement were randomized while the radial pattern of directions was preserved, but at chance with a "speed field" in which the directions were randomized, preserving only magnitude. Accuracy declined with increasing noise in vector directions, but remained below 2.6 degrees with a 90 degrees noise envelope. Thus, the visual system uses the radial morphology of vector directions to determine translational heading and can tolerate large amounts of noise in this pattern. For circular movement, observers were equally accurate with a 2 frame "velocity field", 3-frame "acceleration" displays, and 2-frame and 3-frame "direction fields", consistent with the use of the pattern of vector directions to locate the center of rotation. The results indicate that successive independent velocity fields are sufficient for perception of translational and circular heading. PMID- 1742370 TI - Langevin machine: a neural network based on stochastically justifiable sigmoidal function. AB - In neural networks the activation process controls the output as a nonlinear function of the input; and, this output remains bounded between limits as decided by a logistic function known as the sigmoid (S-shaped). Presently, by applying the considerations of Maxwell-Boltzmann statistics, the Langevin function is shown as the appropriate and justifiable sigmoid (instead of the conventional hyperbolic tangent function) to depict the bipolar nonlinear logic-operation enunciated by the collective stochastical response of artificial neurons under activation. That is, the graded response of a large network of 'neurons' such as Hopfield's can be stochastically justified via the proposed model. The model is consistent with the established link between the Hopfield model and the statistical mechanics. The Langevin function (in lieu of conventional hyperbolic tangent and/or exponential sigmoids) in determining nonlinear decision boundaries, in characterizing the neural networks by the Langevin machine versus the Boltzmann machine, in sharpening and annealing schedules and in the optimization of nonlinear detector performance are discussed. PMID- 1742371 TI - Sequential configuration model for firing patterns in local neural networks. AB - This paper presents a sequential configuration model to represent the coordinated firing patterns of memory traces in groups of neurons in local networks. Computer simulations are used to study the dynamic properties of memory traces selectively retrieved from networks in which multiple memory traces have been embedded according to the sequential configuration model. Distinct memory traces which utilize the same neurons, but differ only in temporal sequencing are selectively retrievable. Firing patterns of constituent neurons of retrieved memory traces exhibit the main properties of neurons observed in multi microelectrode recordings. The paper shows how to adjust relative synaptic weightings so as to control the disruptive influences of cross-talk in multipy-embedded networks. The theoretical distinction between (primarily anatomical) beds and (primarily physiological) realizations underlines the fundamentally stochastic nature of network firing patterns, and allows the definition of 4 degrees of clarity of retrieved memory traces. PMID- 1742372 TI - Cross-talk theory of memory capacity in neural networks. AB - The present paper presents a theory for the mechanics of cross-talk among constituent neurons in networks in which multiple memory traces have been embedded, and develops criteria for memory capacity based on the disruptive influences of this cross-talk. The theory is based on interconnection patterns defined by the sequential configuration model of dynamic firing patterns. The theory accurately predicts the memory capacities observed in computer simulated nets, and predicts that cortical-like modules should be able to store up to about 300-900 selectively retrievable memory traces before disruption by cross-talk is likely. It also predicts that the cortex may has designed itself for modules of 30,000 neurons to at least in part to optimize memory capacity. PMID- 1742373 TI - Simulated bipolar cells in fovea of human retina. III. Effects of chromatic adaptation in bipolar cell spectral responses. AB - Effects of chromatic adaptation on C-type bipolar cells (BC) in human retinal fovea are studied. Adaptation of the r-g channel is linear for both central fovea and parafovea. Adaptation of the parafovea bl-y channel, on the other hand, is nonlinear, which is accounted for by the slower adaptation rate of blue-sensitive cones with white light intensity as compared to rates of red- and green-sensitive cones. Achromatic adaptation of red- and green-center BCs produces uniform response decreases but without unique yellow loci shifts. Achromatic adaptation of blue-center BCs, on the other hand, does cause shifts of the unique green locus. Shifts of the crossover points for the BC response spectra occur with chromatic adaptation; the unique yellow loci shifts to shorter wavelengths with adapting wavelengths shorter than 550 nm and longer wave-lengths with longer adapting wavelengths than 550 nm. Chromatic adaptation is sufficient to explain the Bezold-Bruke effects; but to fully account for these shifts a novel hypothesis is proposed. For the green and red spectrum regions Bezold-Brucke shifts are due to r-g channel chromatic adaptation, while for the blue spectrum region bl-y channel chromatic adaptation accounts for Bezold-Brucke shifts. The two channels function independently in an either/or manner. The bl-y channel, besides having a unique green locus at 517.7 nm, has a crossover point at about 670 nm. Chromatic adaptation of the bl-y channel produces shifts of the unique red locus, which may account for extraspectral hue shifts. PMID- 1742374 TI - Simulated bipolar cells in fovea of human retina. VI. Wavelength discrimination. AB - A computer model of simulated bipolar cells (BC) in the human retina is used to study wavelength discrimination (lambda delta). lambda delta curves are obtained for the two C-types of BCs in the central fovea and the three C-type BCs of the parafovea under various conditions. For the parafovea algebraic addition of the three C-type BCs with proper weighting of the blue-center BC, such that the unique orange locus = 600 nm, gives a combined channel whose lambda delta curve agrees remarkably well with those found in the literature based on human and primate psychophysics. Other studies include effects of chromatic adaptation and dispersion on lambda delta. From this and earlier studies it can be concluded that the center/surround organization of the BCs optimize resolution in the presence of natural occurring dispersion; in addition a specific BC receptive field organization could be picked as being optimal. PMID- 1742375 TI - Symbolic grouping versus simple cell models. AB - The apparent line-like structure in dot patterns derives substantially from the orientation defined by pairings of adjacent dots. Two alternative models have been proposed for making these pairings, one in which the individual dots are treated as discrete grouping tokens, and the second in which the pairing orientation derives from spatial summation by simple cell receptive fields. Contradictory evidence has been found both directly in support of, and directly against, both models. Much of the debate about these two models has hinged on the degree of linearity of summation expected in the simple cell model. Recent neurophysiological evidence changes the balance of the debate, invalidating certain earlier arguments based on linearity and providing a model way of showing that simple cells do indeed play a major, but not necessarily exclusive, role in dot groupings. PMID- 1742376 TI - Relativistic effects in single-joint voluntary movements. AB - We assume that there is an upper limit for the rate of change of controlled variables in the motor control system. Superposition of two single-joint motor programs can lead to a distortion of their simple algebraic summation similar to relativistic Lorenz transformations. Experiments were carried out with the subjects performing fast oscillatory elbow movements on the background of a smooth elbow flexion. Changes in the period of oscillations during the smooth movement were used as index of time transformations. Statistically 5%-7% changes in the period were observed for each of the subjects corresponding to the predictions of the model. PMID- 1742377 TI - Computation of frequency-to-spatial transform by olfactory bulb glomeruli. AB - A physiological simulation of 2.5% of the input and inhibitory neurons and 25% of the primary mitral/tufted cells in a single mammalian olfactory bulb glomerulus was constructed. This physiological simulation used the integrate-and-fire paradigm with realistic activation curves and synaptic delays. The dendritic integration incorporated non-linear interactive effects of individual cell excitatory and inhibitory post-synaptic potentials (PSPs) from both axodendritic and dendro-dendritic synaptic contacts. Refractory periods for granule-cell inhibition of mitral/tufted cell activity lead to relatively fixed-frequency rhythmic activity in the glomerulus, independent of the input frequency from the olfactory nerve. Though the frequency of mitral/tufted cell firing in bulb was approximately independent of input frequency, the number of cells active in the glomerulus was a roughly-linear function of input frequency to the glomerulus, indicating the mechanism's ability to function as a frequency-to-spatial encoder. PMID- 1742378 TI - In search of the causes of appendicitis. PMID- 1742379 TI - Do oral contraceptives cause breast cancer? PMID- 1742380 TI - The epidemiology of acute appendicitis in California: racial, gender, and seasonal variation. AB - The incidence of acute appendicitis has been reported to vary substantially by country, geographic region, race, sex, season, and occupation, but the reasons for this variation are unknown. We evaluated several risk factors for appendicitis by analyzing data from hospital discharge abstracts on all cases of acute appendicitis treated surgically in nonfederal hospitals in California from 1983 to 1986 (N = 102,546). Comparison of age and sex-specific incidence rates for four racial/ethnic groups (white, Hispanic, black, and Asian/other) revealed rates in blacks and the Asian/other group one-half or less of the rates for whites and Hispanics between the ages of 5 and 29 years. Incidence rates in males were higher than rates in females in all racial/ethnic groups for most ages (RR = 1.1-1.7). Seasonal variation in incidence was modest. Peak rates occurred in July, August, and September, and the lowest rates occurred in December. Hypotheses about the etiology of appendicitis must account for substantial racial/ethnic, gender, age variation, and modest seasonal variation in the incidence. PMID- 1742381 TI - Study designs for dependent happenings. AB - In 1916, Sir Ronald Ross defined "dependent happenings" as events where the number affected in a unit of time depends on the number already affected. That is, the incidence depends on the prevalence, a characteristic of many infectious diseases. Because of this dependence, interventions against infectious diseases can have not only direct protective effects for the person receiving an intervention, but also indirect effects resulting from changes in the intensity of transmission in the population. This paper develops the conceptual framework for four types of study designs that differentiate and account for direct and indirect effects of intervention programs in dependent happenings. PMID- 1742382 TI - Prognostic modeling of clinical outcomes: an illustration with data from patients with membranous nephropathy. AB - Probabilities that a patient will occupy any of five clinically defined compartments at different future times are generated and graphed by a personal computer. The probabilities are functions of a patient's relevant baseline characteristics (treated or control group), clinical status, and follow-up time at which the prognosis is made. The illustrative prognostic model is based on a reanalysis of detailed individual records for 81 patients with idiopathic membranous nephropathy (42 treated with methylprednisolone and chlorambucil; 39 controls) in a randomized clinical trial. The compartments to and from which patients may pass are identified as (1) complete remission, (2) partial remission, (3) the nephrotic syndrome, (4) renal failure, and (5) death. Estimated risk functions for transitions between compartments involve baseline treatment, and intermediate and temporal variables, together with their relevant interactions. The model illustrates how, despite the overall advantage of treated over control patients, the comparative prognoses can change greatly and can even sometimes be reversed, depending on a variety of follow-up experiences. PMID- 1742383 TI - Black-white differences in blood pressure among participants in NHANES II: the contribution of blood lead. AB - Separate studies using data from the second National Health and Nutrition Examination Survey, 1976-1980 (NHANES II) have shown that blacks in the United States have higher blood lead levels than whites and that blood lead is positively related to blood pressure. Based on these reports, we examined data from NHANES II to determine the extent to which race differences in blood pressure were explained by elevated blood lead levels in blacks. Regression analyses, with race as an indicator variable, were used to estimate the contribution of blood lead to black-white differences in blood pressure. The overall effect of blood lead on race differences in blood pressure was small, reflecting, in part, the magnitude of race differences in blood lead and in the association of blood lead and blood pressure. Nevertheless, a pronounced and consistent effect of lead on race differences in blood pressure was found among the poor, particularly women. PMID- 1742384 TI - Breast cancer risk and oral contraceptive use: results from a large case-control study. AB - The association between oral contraceptive use and breast cancer risk was examined using data from a case-control study of breast cancer in Long Island, New York. Cases were defined as female residents of Nassau and Suffolk Counties between the ages of 20 and 79, diagnosed with breast cancer between January 1, 1984 and December 31, 1986. Age- and county-matched controls were selected from driver's license files. Among all women under age 70 at diagnosis, there was no association between oral contraceptive use and breast cancer; there was, however, a positive association in the subgroup ages 20-49 (adjusted odds ratio = 1.68, 95% CI: 1.16-2.42). Risk increased with increasing duration of use, but did not differ between women who first used oral contraceptives before the first pregnancy and those who first used them later, or between women who first used oral contraceptives before age 25 and those who first used them at a later age. Risk also appeared to increase with number of years of use before the first pregnancy or before age 25, although numbers were small. History of benign breast disease did not influence risk. The association of breast cancer risk with oral contraceptive use appeared stronger in women from Suffolk County than Nassau County. PMID- 1742385 TI - An efficient program for computing conditional maximum likelihood estimates and exact confidence limits for a common odds ratio. AB - This paper describes a method and associated computer program for calculating exact confidence limits and P values, along with the conditional maximum likelihood estimate of the common odds ratio for a series of 2 x 2 tables. The program can be used to calculate exact estimates for matched data and is considerably faster than others currently available. PMID- 1742386 TI - Using logistic regression to estimate the adjusted attributable risk of low birthweight in an unmatched case-control study. AB - Other authors have shown how to estimate attributable risk based on stratification. In this paper, we show how to estimate adjusted attributable risks, standard errors, and confidence intervals from an unmatched case-control study that has population-based controls and uses the logistic regression model to estimate relative risk. We apply the method to data from a case-control study of low birthweight. The method is conceptually simple, has no assumptions beyond those of the logistic model, makes use of computer-intensive statistical techniques (the bootstrap), and extends to interactions. A Fortran computer program to carry out the computations is available from the authors upon request. PMID- 1742387 TI - On the origin of Hill's causal criteria. AB - The rules to assess causation formulated by the eighteenth century Scottish philosopher David Hume are compared to Sir Austin Bradford Hill's causal criteria. The strength of the analogy between Hume's rules and Hill's causal criteria suggests that, irrespective of whether Hume's work was known to Hill or Hill's predecessors, Hume's thinking expresses a point of view still widely shared by contemporary epidemiologists. The lack of systematic experimental proof to causal inferences in epidemiology may explain the analogy of Hume's and Hill's, as opposed to Popper's, logic. PMID- 1742388 TI - Coffee consumption, birthweight, and reproductive failures. AB - We studied the effect of coffee consumption on birthweight, preterm births, and congenital malformations. From April 1985 to April 1987, 11,858 pregnant women out of 13,815 in two Danish cities responded to a mailed questionnaire on eating and drinking habits during pregnancy. Data on pregnancy outcomes were recorded from medical files. Maternal coffee consumption of four cups a day or more was associated with a moderate decrease in birthweight, especially among smokers. The associations between coffee consumption and preterm births or congenital malformations were very weak. PMID- 1742389 TI - Results and effect of refusal recontact in a case-control study of ectopic pregnancy. AB - In a population-based study of ectopic pregnancy, a card-back system of initial subject contact yielded a positive response from 85.1% of potential cases and 65.0% of potential controls. We subsequently recontacted by telephone potential controls who had declined to participate and offered them $10 compensation for participation. We recontacted 205 of the 330 control women who had refused to participate. Twenty-eight were found to be ineligible, and 75.7% of the remaining 177 agreed to participate on recontact. The additional 125 women were not recontacted, 9 because of firm initial refusals and 116 because the study ended before contact could be sought or made. Controls who initially declined to participate but subsequently agreed differed from those who initially agreed on a number of demographic and reproductive characteristics, and estimates of ectopic pregnancy risk associated with induced abortion and tubal sterilization changed slightly with the inclusion of initial nonparticipants. We conclude that use of a card-back system of subject contact yields a low level of positive response among reproductive-aged women and that many initial nonparticipants can be converted into participants by personal contact and the offer of compensation. PMID- 1742390 TI - The effect of an informational newsletter on control participation rates: a randomized study. AB - We employed a randomized study of 344 subjects to determine whether an initial contact letter accompanied by an informational newsletter increased participation in a population-based case-control study. The results indicated that there was no benefit in including a newsletter with a letter of introduction. There may have been a slight detrimental effect, since those who received the newsletter were less likely to consent to an in-person interview (82%) than those who did not (88%). PMID- 1742391 TI - In defense of standardized regression coefficients. AB - The association between a risk factor and a disease can be expressed as a standardized regression coefficient derived from a logistic model. When exponentiated, this standardized coefficient equals the odds ratio associated with a one-standard-deviation change in the risk factor. Some epidemiologists have recently recommended that standardized regression coefficients not be used in epidemiologic research. We disagree and provide examples that demonstrate that, when a risk factor is continuous, standardized regression coefficients may be helpful for comparing variables measured in different units. Standardized regression coefficients may also be helpful for comparing the effect of the same risk factor in different populations. Misinterpretations can be avoided if the standard deviations of the variables of interest are also provided. There is no reason to abandon the use of standardized regression coefficients in epidemiologic analyses. PMID- 1742392 TI - Standardized regression coefficients: a further critique and review of some alternatives. PMID- 1742393 TI - On the use of standardized regression coefficients. PMID- 1742394 TI - Exogenous hormones and colorectal cancer. PMID- 1742395 TI - [Critical evaluation of preoperative instrumental staging of rectal tumors. Research on the adequate use of US, CT and MR]. AB - Both traditional exams (rectal exploration, rectoscopy, barium enema, CEA) and advanced imaging (31 US, 40 CT and 11 MR) were performed for preoperative evaluation of rectal carcinoma in order to assess the accuracy of radiological imaging in the T and N staging. The results obtained have not been considered satisfactory and it is felt that US, CT and MR should not be employed routinely for rectal staging. Indeed accuracy of US, CT and MR is respectively 64%, 75% and 81% in the T evaluation and 64%, 70% and 64% in the N staging. In order to evaluate the effective usefulness of these three latter imaging techniques a double therapeutical choice was proposed. The first treatment option was suggested on the basis of traditional staging while a second choice was given considering US, TC and MR data also. Operatory findings subsequently allowed a definitive judgement on the influence of the different techniques on treatment selection. US has furnished useful data that could have allowed us to modify treatment in one case while in 5 other cases diagnostic error would have influenced treatment negatively. CT was useful in 5 cases while in 7 cases it would have influenced treatment choice negatively. MR would have been useful in one case and harmful in another. It is concluded that only patients with large neoplasms (stages T3 and T4) benefit from CT and MR staging with the exception of those cases that have tumors above the peritoneal fold or in strict relation with the sphincter structures. US was useful only in evaluating relations of neoplasms of the anterior rectal wall with nearby pelvic structures. PMID- 1742396 TI - [Morpho-functional characteristics of reflux gastritis in patients after cholecystectomy and without cholecystectomy]. AB - The aim of this study was to evaluate some biochemical and histopathological aspects in a group of patients with a view to identifying any differences depending on whether the pathology was associated with previous cholecystectomy or idiopathic. The study involved 23 patients (8 post-cholecystectomy cases and 15 ulcer-free dyspeptic patients) with the diagnosis of duodenogastric reflux gastritis confirmed by endoscopic histopathological evaluation. The following parameters were considered: 1) pH and bile salt concentration in gastric juice; 2) histological classification of antral biopsies (Niemela's criteria); 3) dyspeptic symptoms (dyspepsia, pyrosis and epigastric pain, sense of repletion, foul-tasting mouth) graded on a scale from 0 to 4. All parameters were considered in relation to whether or not Helicobacter Pylori was found in the histological specimens. No significant differences were found between the two groups for pH and bile salt values or for Helicobacter Pylori positivity. No relationship was observed between the Helicobacter Pylori and either the severity of the histological picture, the features of the biochemical parameters or the severity of the clinical symptoms. Such findings confirm the common pathophysiological pattern of reflux gastritis regardless of any permanent biliary tract alterations and the low importance of Helicobacter Pylori infection in determining this syndrome. PMID- 1742397 TI - [Nutritional assessment of aged patients with fractures of the proximal epiphysis of the femur]. AB - Forty-two patients (M/F 9/33; age 78 +/- 10 years) were studied during Hospital stay for femoral neck fractures (16 neck, 26 pertrochanteric fractures). All underwent fracture surgery (internal fixation in 30, arthroplasty in 12 patients). Food intake was evaluated daily, supplemented with specific recipes. Biochemical assessment of nutritional status (hemoglobin, hematocrit, total proteins, albumin, prealbumin, Na, K, Ca, Fe, P, Mg) was performed before and after surgery. Nitrogen balance was evaluated in 8 patients in the post-operative period (40 determinations). The study group was compared for post-surgical complications and mortality during Hospital stay with a historical control group without any nutritional survey. Mean daily caloric intake was (M +/- DS) 1014 +/- 360 in the preoperative period, 960 +/- 210 and 1036 +/- 185 postoperatively (5-9 and 10-15 days post-surgery, respectively). Mean nitrogen intake was, respectively, 7.5 +/- 2.6, 7 +/- 2.1, 6.9 +/- 1.6 gN/day. No significant differences were found. In the preoperative period, the following tests were found below the normal range: iron (median 30 micrograms/dL), albumin (median 3.1 g/dL), hemoglobin (median 12 g/dL) hematocrit (median 35%). After surgery, they decreased significantly; also prealbumin, in normal limits before surgery (20 +/- 0.7 mg/dl), decreased significantly 5-9 days after surgery. After 10-15 days from surgery, only prealbumin and iron reached the preoperative level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742398 TI - [Eosinophilic gastroenteritis and ascites. Clinical case]. AB - We report the case of a patient with recurrent subocclusive episodes and diarrhea (no malabsorption) associated with ascites, in the absence or liver, kidney or heart disease. The demonstration of hypereosinophilia in the peripheral blood and in the ascites fluid and the failure to identify parasitic or haematological disorders have led to a through examination of the stomach (Endoscopy, Echoendoscopy), small bowel (X-rays and Computerized Axial Tomography) and colon (colonoscopy) in a search for parietal lesions. The absence of segmental lesions and the observation of CAT images of diffuse, regular thickening of the ileum and of the mesentery, coupled with the monotonous clinical history spanning over three decades, have led to a diagnosis of eosinophilic gastroenteritis with involvement of the serosal layer. Serosal involvement is rare in eosinophilic disease of the gut; in analogy with other cases reported in the literature, steroids have improved clinical symptoms and normalized the hematological picture. PMID- 1742399 TI - [Diagnostic routine in hepatology]. PMID- 1742400 TI - [Therapy of chronic non-A, non-B hepatitis with interferon alfa-2B. A controlled clinical study and long-term follow-up]. AB - In order to assess the efficacy of alpha-2b interferon (r-IFN) in the treatment of non-A non-B chronic hepatitis, 30 patients were randomised to receive r-IFN (3 MU subcutaneously three times a week for 24 weeks) or no therapy. A total of 21 males and 9 females, aged between 24-66 years old and who had had increased transaminase levels for at least one year, were included in the study. Three patients were ex-drug addicts and 6 had received blood transfusions whereas the cause of the infection in the remaining 21 patients was unknown. Hepatic biopsies performed prior to the study revealed persistent chronic hepatitis in 7 patients, active chronic hepatitis (ACH) in 19 patients and ACH with hepatic cirrhosis in 4 patients. Anti-HCV antibodies were present in 21 patients (70%). Transaminase values returned to normal in 11 (73%) of the 15 patients treated and remained unchanged in controls after 6 months of therapy. During the 18-month follow-up following the suspension of r-IFN treatment, transaminase values rose again to pre-treatment levels in 4 patients. Anti-HCV antibodies did not disappear in any of the patients who responded to therapy. PMID- 1742401 TI - [Evaluation of the arterial share of portal flow using a scintigraphic technique in patients with liver cirrhosis. Correlations with other parameters of portal hypertension]. AB - This study aimed to measure in semiquantitative terms the arterial-venous ratio of the portal flow using a scintigraphic technique, by means of a simple intravenous injection of a 99mTcDiethylHIDA bolus, a method which was found to be extremely simple and non-invasive, with a good degree of repeatibility. The percentage of arterialisation of the portal flow was found to be higher in cirrhotic patients compared to non-hepatopathic subjects, and among cirrhotic patients it was correlated with the severity of disease, the presence and degree of esophageal varices, and the presence of porto-systemic shunts, assessed using the ammonium chloride test. PMID- 1742402 TI - [Treatment of biliary stenosis with expandable metallic prostheses]. PMID- 1742403 TI - Evolution and facial action in reflex, social motive, and paralanguage. AB - Based upon current evolutionary theory and recent laboratory and field data, this paper introduces a behavioral-ecology view of human facial displays that contrasts with previous views of faces as innate, prototypic, "iconic" expressions of fundamental emotions. First, I detail the criteria for establishing genetic and epigenetic contributions to facial behavior. Under these criteria, cross-cultural communality in canonical facial displays implies neither their genetic control nor their fundamental relation to emotion. New findings reestablish phylogenetic continuity by showing that human facial displays and vigilance for them, like their nonhuman counterparts, coevolve in the service of social motives; faces issued in solitude typically reflect imaginary or implicit interaction. Two evolutionary trends are probably involved in shaping facial actions--emancipation of reflexes, and automatization of instrumental acts. Modern conceptions of genetic and cultural evolution, and knowledge about animal signaling, suggest new hypotheses regarding the origins and functions of facial displays. In so doing, they clarify how facial displays relate to reflexion, motive and intention, emotion and psychophysiology, and language and paralanguage. PMID- 1742404 TI - Controlled and modulated release of basic fibroblast growth factor. AB - Basic fibroblast growth factor has multivariate effects in stimulating cell growth and the processes that surround tissue repair. Pathophysiologic studies have been hampered by the stability of the compound. Though very potent, basic fibroblast growth factor is rapidly degraded when injected or ingested. Controlled release of basic fibroblast growth factor would allow for examination of the chronic effects of this compound. Conventional matrix polymer-based release devices were fabricated and basic fibroblast growth factor released in a sustained fashion, but 99% of basic fibroblast growth factor mitogenic activity was lost. The source of these losses was identified and preventative measures examined. Preservation and stabilization of basic fibroblast growth factor was accomplished by binding the factor to heparin-Sepharose beads. This permitted prolonged storage, repeated handling, and the encapsulation of basic fibroblast growth factor within a microspherical controlled-release device using a naturally occurring polymer material, alginate. Encapsulation was accomplished with 77% efficiency and 87.5 +/- 12% of the basic fibroblast growth factor was released in a biologically active form. Release activation and regulation was achieved when cleavage of the basic fibroblast growth factor-heparin bonds was enhanced (e.g. by enzymatic bond cleavage with heparinase). Kinetic profiles were identified for a variety of experimental conditions and the effects of the controlled release of basic fibroblast growth factor on BALBc/3T3 fibroblasts examined. PMID- 1742405 TI - Stress-enhanced ion release--the effect of static loading. AB - Static stresses affect the corrosion behaviour of 316L stainless steel, Ti-6AI 4V, and a Co-Cr-Mo alloy. Several corrosion parameters are modified by stress, although the changes most relevant to the clinical situation are lowering of breakdown potentials and increases in corrosion currents. AC impedance techniques to measure capacitance allowed the latter effect to be partitioned into components of true current density and true area changes. Although loading past the yield point can definitely cause stress-enhanced ion release (SEIR), it is not required. SEIR can also be caused by elastic loading. The basic mechanism for this phenomenon appears to be passive film disruption followed by slow repassivation kinetics. Polished, grit-blasted, and porous-coated surfaces were examined. The porous-coated materials seemed to be most susceptible to SEIR. If effects similar to those observed here apply to in vivo conditions, then tests on unstressed alloys in vitro could grossly underestimate ion release rates of stressed implant devices in vivo. PMID- 1742406 TI - Anticancer gelatin microspheres with multiple functions. AB - Biodegradable, hydrophilic gelatin microspheres (GM) with an average diameter of 70 microns were prepared by cross-linking gelatin with glutaraldehyde for hepatic intra-arterial infusion. An anticancer agent, mitomycin C (MMC), together with a radioisotope, 131I, were bound to the GM for chemotherapy and local internal radiotherapy. The 131I-labelled MMC-GM (131I-MMC-GM) could accumulate in the specific site and embolize the hepatic arteries after the hepatic intra-arterial infusion, while it caused various effects to the liver cells. The 131I-MMC-GM remained within the hepatic arteries for at least one month. In vitro release of drugs from the GM was also quantified using a dynamic dialysis method. PMID- 1742407 TI - Heterocyclic methacrylates for clinical applications. I. Mechanical properties. AB - The mechanical properties of a number of heterocyclic and one cyclic methacrylate have been studied for their potential in low polymerization shrinkage systems. This study included both homopolymers and room temperature polymerizing systems using poly(ethyl methacrylate) powder with a heterocyclic methacrylate monomer. The one cyclic methacrylate studied, isobornyl methacrylate, gave an extremely brittle polymer; furthermore, it would not form a dough with poly(ethyl methacrylate). The homopolymers gave Young's moduli in the range 1.38-2.19 GN/m2, i.e. lower than poly(methyl methacrylate). The moduli of poly(ethyl methacrylate)/monomer systems are theoretically predictable from the moduli of the homopolymers involved. The above materials were generally ductile and the mechanical properties indicated a useful class of materials for clinical use. PMID- 1742408 TI - Heterocyclic methacrylates for clinical applications. II. Room temperature polymerizing systems for potential clinical use. AB - A number of useful room temperature polymerizing resins were formulated, based on poly(ethyl methacrylate) powder and a range of low shrinkage heterocyclic methacrylate monomers. N,N-dimethyl-p-toluidine or p-tolyl diethanolamine were used as activating amines, but the latter material is less active and some care is necessary with respect to the source of the monomer. Isobornyl methacrylate is a useful diluent monomer to reduce the exotherm. PMID- 1742409 TI - Heterocyclic methacrylates for clinical applications. III. Water absorption characteristics. AB - The water absorption and desorption behaviour of poly(isobornyl methacrylate) and poly(tetrahydropyran-2-ylmethyl methacrylate) obeyed diffusion laws on repeated absorption/desorption cycles. However, the polymers of 2,3-epoxypropyl, tetrahydrofurfuryl and tetrahydropyranyl methacrylates did not obey diffusion laws, did not equilibrate after 2 yr immersion in water and exhibited very high uptake values (30-90%). For 2,3-epoxypropyl methacrylate, the sample disintegrated. A clearly detailed structure of the heterocyclic ring is critical. The use of these monomers in room temperature polymerizing poly(ethyl methacrylate)/monomer systems generally reflected the behaviour of the related homopolymers. PMID- 1742410 TI - Long-term flexural strength of glass ionomer cements. AB - The flexural strength of five glass ionomers was measured at intervals ranging from 1 h to 3 months after mixing. The pattern of change in flexural strength is material-specific with two water-activated materials having significantly higher long-term flexural strengths than the others. This may be attributable to the different polyacrylic acids used or to changes in the glass formation in the different materials. PMID- 1742411 TI - Relationship between chemotaxis and complement activation by ceramic biomaterials. AB - This paper examines the relationship between complement activation by ceramic biomaterials and chemotaxis. Complement activation was examined by both neutrophil polarization (a technique which has previously been used to examine chemotaxis) and immunoelectrophoresis assays. The results suggest that at increasing serum concentrations of both calcium hydrogen phosphate and coral (calcium carbonate) powder, the quantity of C3 activation increased, as did the quantity of serum-derived chemotactic factors. In the case of tricalcium phosphate powder, the quantity of C3 activation and the neutrophil polarization response to serum were similar for serum levels between 20 and 80 mg/ml. Complement C3 was not activated in serum incubated with calcium hydrogen phosphate powder and serum incubated with this material was not chemotactic for neutrophils. PMID- 1742412 TI - Effect of carboxylate and/or sulphonate ion incorporation on the physical and blood-contacting properties of a polyetherurethane. AB - Propyl sulphonate and ethyl carboxylate groups were grafted on to the backbone of a polytetramethylene oxide-based polyurethane (PEU). The effects of ion type and ion content on the polymer's bulk, surface, and blood-contacting properties were evaluated. Ion incorporation disrupted the packing of the hard segment but had little effect on the overall microphase separation of the polymers. The mechanical properties of the ionomers were improved relative to the base PEU, although the carboxylate-containing ionomers were weaker than the sulphonate containing polymers. As expected, the polymer's water absorption and surface polarity increased with increasing ion content. Dynamic and static contact angle analysis indicated that the propyl sulphonate-containing polymers were more polar than the ethyl carboxylate-containing polymers at the same ion content which is attributed to the higher ionic strength of the sulphonate ion. The carboxylate containing polymers had no statistically significant effect on the polymer's canine ex vivo blood-contacting response. At the same ion content, propyl sulphonate incorporation significantly reduced platelet deposition for very short blood-contacting times. When both ion types were present in the polymer, the propyl sulphonate group appeared to be the primary factor determining the polymer's blood-contacting response. The polymer containing 20 mol% propyl sulphonate groups significantly reduced platelet deposition and activation while also exhibiting enhanced fibrinogen deposition. PMID- 1742413 TI - Study of the calcification of bovine pericardium: analysis of the implication of lipids and proteoglycans. AB - A major problem with cardiac bioprosthesis is the calcification of the tissue used in their manufacture, an event which may be promoted by multiple factors. A subcutaneously implanted model was used to determine, by selective extractions of proteoglycans and lipids, the role played by these compounds in the calcification of the bovine pericardial tissue used in the construction of some biological valves. The selective extraction of proteoglycans resulted in a great accumulation of calcium salts in the tissue, which, moreover, had a reduced hydrothermal stability. On the other hand, lipid extraction produced no modification in the stability of the tissue and resulted in a lesser calcium accumulation than in the control group. Proteoglycans and lipids may, therefore, be implicated in mineralization of the pericardial tissue. PMID- 1742414 TI - Cytocompatibility of two coating materials, amorphous alumina and silicon carbide, using human differentiated cell cultures. AB - The cytocompatibility of two coating materials, amorphous alumina and silicon carbide deposited by radio-frequency sputtering, was studied using alveolar bone osteoblasts and gingival fibroblasts from human healthy tissues. Cytocompatibility was assessed at the level of both the basic (attachment, proliferation and cell protein content) and the specific features (intracellular alkaline phosphatase activity and the cytoskeleton) of the cells in direct contact with the coating. Titanium was used as the reference material. The results showed that both silicon carbide and amorphous alumina are cytocompatible for human fibroblasts and osteoblasts, whereas titanium appears the least cytocompatible of all the three substrates. Moreover, the amorphous alumina coating seems slightly bioactive. It seems that these coatings, particularly amorphous alumina, could be used to protect alloys against corrosion, and consequently combine the good mechanical properties of the alloys with the good biocompatibility of the coatings. These coatings seem to perform more suitably than titanium if the strength of the bond between the coating and the underlying alloys is strong enough to give a stable composite material. PMID- 1742415 TI - Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro. AB - Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed. PMID- 1742416 TI - Biocompatibility of a prolonged-action antialcohol preparation. AB - Acid and alkaline phosphatase activities in liver lysosomes and liver mitochondria, respectively, as well as in connective tissue capsule were studied for an antialcohol preparation (polyurethane carrier and disulfiram at 150, 300 and 625 mg/kg body weight) implanted subcutaneously. Increased acid phosphatase activity was observed in connective tissue capsule on days 14, 30 and 90 after implantation and in liver lysosome fraction on days 14 and 30 with preparation containing disulfiram at 300 and 625 mg/kg body weight. Alkaline phosphatase activity increased both in connective tissue capsule and in liver mitochondria up to day 30 only when sample with maximal disulfiram dose was implanted. Acid phosphatase activity is an adequate indicator for biocompatibility of prolonged action medicine preparations. The data obtained show that the suggested medical form containing disulfiram 150 mg/kg body weight is biocompatible. Interaction between acid and alkaline phosphatase activity changes and biocompatibility and destruction of polymer implants is discussed. PMID- 1742417 TI - Tooth movement. AB - This article reviews the evolution of concepts regarding the biological foundation of force-induced tooth movement. Nineteenth century hypotheses proposed two mechanisms: application of pressure and tension to the periodontal ligament (PDL), and bending of the alveolar bone. Histologic investigations in the early and middle years of the 20th century revealed that both phenomena actually occur concomitantly, and that cells, as well as extracellular components of the PDL and alveolar bone, participate in the response to applied mechanical forces, which ultimately results in remodeling activities. Experiments with isolated cells in culture demonstrated that shape distortion might lead to cellular activation, either by opening plasma membrane ion channels, or by crystallizing cytoskeletal filaments. Mechanical distortion of collagenous matrices, mineralized or non-mineralized, may, on the other hand, evoke the development of bioelectric phenomena (stress-generated potentials and streaming potentials) that are capable of stimulating cells by altering the electric charge on their membrane or their fluid envelope. In intact animals, mechanical perturbations on the order of about 1 min/d are apparently sufficient to cause profound osteogenic responses, perhaps due to matrix proteoglycan-related "strain memory". Enzymatically isolated human PDL cells respond biochemically to mechanical and chemical signals. The latter include endocrines, autocrines, and paracrines. Histochemical and immunohistochemical studies showed that during the early places of tooth movement, PDL fluids are shifted, and cells and matrix are distorted. Vasoactive neurotransmitters are released from periodontal nerve terminals, causing leukocytes to migrate out of adjacent capillaries. Cytokines and growth factors are secreted by these cells, stimulating PDL cells and alveolar bone lining cells to remodel their related matrices. This remodeling activity facilitates movement of teeth into areas in which bone had been resorbed. This emerging information suggests that in the living mammal, many cell types are involved in the biological response to applied mechanical stress to teeth, and thereby to bone. Essentially, cells of the nervous, immune, and endocrine systems become involved in the activation and response of PDL and alveolar bone cells to applied stresses. This fact implies that research in the area of the biological response to force application to teeth should be sufficiently broad to include explorations of possible associations between physical, cellular, and molecular phenomena. The goals of this investigative field should continue to expound on fundamental principles, particularly on extrapolating new findings to the clinical environment, where millions of patients are subjected annually to applications of mechanical forces to their teeth for long periods of time in an effort to improve their position in the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742419 TI - Cell surface carbohydrates are markers of differentiation in human oral epithelium. AB - Carbohydrates of the epithelial cell membrane are involved in cell-cell and cell substrate interaction, and changes are seen in relationship to cell differentiation and neoplastic transformation. The terminal part of carbohydrate structures carried on oral epithelial cells often expresses antigens of the ABO and Lewis blood group systems. The expression of these antigens are in oral mucosa genetically regulated by the A, B, H, Lewis, and secretor genes with subsequent correspondence between the blood group antigens expressed on erythrocytes and on oral epithelial cells. Variation in expression of carbohydrates is also seen in relationship to terminal differentiation in that blood group antigens and their immediate precursor structures are sequentially expressed on cells during their pathway through the epithelium. Various organs and tissues differ in their expression of cell surface carbohydrates. In oral mucosa, a close relationship is seen between the type of tissue differentiation and expression of blood group antigen; keratinized, nonkeratinized, and junctional epithelium all show different patterns of carbohydrate expression. PMID- 1742418 TI - Cell adhesion proteins in oral biology. PMID- 1742420 TI - Enhanced expression of heat shock protein gene in kidney lymphoid cells of lupus prone mice during growing process. AB - In the present study, the spontaneous elevation of the transcription of heat shock protein (hsp 70) gene in kidney lymphoid cells of lupus-prone mice (MRL lpr/lpr) is shown by Northern blot and nuclear run on transcription assay. By quantification analysis of hsp 70 gene transcription, more than ten times of the enhanced transcription of hsp 70 gene in kidney lymphoid cells of lupus-prone mice was first found, in comparison to normal control mice (MRL(-)+/+). The elevation of transcriptional level of hsp 70 gene was also found to increase during growing process and seemed to have positive correlation with deterioration of lupus-related renal disorders in lupus-prone mice. Our observation suggests that heat shock proteins may be involved in possible significance in the pathophysiology of nephrotic lesions of lupus-prone mice due to lupus-related change of kidney lymphoid cells. PMID- 1742421 TI - Treatment with IL2/vaccinia recombinant virus leads to serologic, histologic and phenotypic normalization of autoimmune MRL/lpr-lpr mice. AB - We have analyzed the effect of IL2 administered in vivo on both the lymphoproliferation and autoimmune disease progression of MRL/lpr mice. Human IL2 was delivered by infecting MRL/lpr mice with vaccinia virus recombinants at different stages of lpr disease. The results reported here showed that treatment of lpr mice with IL2 mediated: (1) restored normal thymic differentiation illustrated by an expansion of the double positive population accompanied by increased numbers of mature thymocytes; (2) depletion of the peripheral CD3+ CD4- CD8- (DN) T-cell population; (3) normalization in the pattern of TcRV beta gene expression displayed by mature T cells; (4) decreased urine-protein levels and immune complex deposition in the kidney, with a resultant absence of glomerulonephritis; and (5) an increased longevity (from 195 to more than 400 days). We speculate that the dramatic reduction in the abnormally expanded CD3+ DN T-cell population following IL2 therapy might be directly related to the amelioration and/or prevention of autoimmune disease in these mice. Collectively, these results suggest that diseases showing a selective expansion of DN cells should be envisaged as possible targets for the treatment described here. PMID- 1742422 TI - Analysis of the IgG subclass production from rheumatoid arthritis synovial cell cultures. AB - In man there are four subclasses of IgG which differ from each other with respect to their biological properties. Some evidence suggests that the production of IgG3 is unusually high in rheumatoid synovia. In this study secretion of IgG subclasses by synovial lymphocytes in vitro was measured using sensitive subclass specific ELISAs. It was found that, in both synovial membrane- and synovial fluid derived cell cultures, the general pattern of IgG subclass secretion was IgG1 greater than 2 greater than 3 greater than or equal to 4, and that, in most cultures, IgG3 was a minor subclass accounting, on average, for only 8% of the total IgG. This was similar to the percentage of this subclass in normal human serum and in culture supernatants from the patients' peripheral blood lymphocytes. PMID- 1742423 TI - Isotype and immunoglobulin subclass distribution of eye muscle membrane reactive antibodies in the serum of patients with thyroid-associated ophthalmopathy as detected in Western blotting. AB - We have determined the immunoglobulin (Ig) class (isotype) and IgG subclass of autoantibodies in the serum of patients with thyroid-associated ophthalmopathy (TAO) or autoimmune thyroid disorders without evident ophthalmopathy reactive in Western blotting with antigens of 55, 64, 75 and 95 kDa in pig eye muscle membrane (PEMM). The 22 sera studied were shown, previously, to contain IgG antibodies reactive with one or more of the four antigens. The majority of sera antibodies reactive with PEMM antigens were of two or more IgG subclasses. Of the IgG subclass specificities IgG3 and IgG4 subclass antibodies were, overall, the most common. We were unable to demonstrate IgG subclass restriction for antibodies reactive with the 95 or 55 kDa antigens in PEMM, antibody activity being equally distributed in all four subclasses tested. While most of the sera which recognized a 64 kDa antigen did so with an IgG4 antibody, all other subclasses were also represented. On the other hand all 13 sera reactive with a 75 kDa antigen did so using Ig of the IgG3 subclass and 12 of these used the IgG4 subclass as well, IgG1 and IgG2 subclasses being represented in only 3 and 4 sera, respectively. There were no differences, in respect to Ig class or IgG subclass distribution of eye muscle reactive antibodies between patients with Graves' hyperthyroidism with ophthalmopathy and those with Hashimoto's thyroiditis, and eye disease. Control sera from five normal subjects and three patients with nonautoimmune thyroid disorders did not contain antibodies reactive with these PEMM antigens of any Ig class or IgG subclass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742424 TI - The functional state of the beta cells in the pathogenesis of insulin-dependent diabetes mellitus. AB - Besides the thymus-dependent immune system, growing evidence suggests that the functional state of the beta cell plays a role in the pathogenesis of Type 1 (insulin-dependent) diabetes. Increased incidence of diabetes has been described after increased insulin production and vice versa, and actual hyperinsulinemia has been observed in relation to the diabetogenesis. Prophylactic insulin treatment and intensive insulin therapy at diagnosis are discussed. The studies referred to are mostly animal model investigations of BB rats and NOD mice and-to a lesser degree- of streptozotocin- and encephalomyocarditis-virus-induced diabetes. Also human evidence exists, but naturally of a more sporadic character. Three possible mechanisms behind the beta cell sensitivity as a function of their activity are suggested: increased antigen expression (including both gangliosides and proteins) in beta cells with high activity which could activate the destruction caused by the immune system, and increased susceptibility to the toxicity of interleukins and to diabetogenic agents. With respect to developing preventive treatment the described research area may turn out to be very important. Further studies both in animal models and in humans are awaited. PMID- 1742425 TI - Local IgA and IgM rheumatoid factor production in autoimmune MRL/lpr mice. AB - Spontaneous local immunoglobulin (IgA, IgG, IgM) as well as IgA and IgM rheumatoid factor (RF) production in salivary glands, lymph nodes, and spleen was analyzed at various ages in autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice by using an ELISPOT assay. The longitudinal design of the study permitted correlations with severity of disease in salivary glands (sialadenitis). Local production of immunoglobulins in salivary glands and lymph nodes occurred with a pattern of IgG much greater than IgM greater than IgA. This isotype pattern differed from that simultaneously observed in spleen where IgG did not predominate to the same extent. Moreover, the spleen was the major site of IgM production. Rheumatoid factors constituted a significant fraction of local IgA and IgM in involved salivary glands. The pattern of IgA RF isotype expression in salivary glands contrasted with that observed in spleen. While the number of IgA and IgG secreting cells increase at an early age, the peak of RF production in salivary glands occurs in older mice. Furthermore, the level of immunoglobulin secretion was positively correlated with disease severity in salivary glands. The results suggest that local RF production is a secondary event in salivary gland inflammation in MRL/1pr mice rather than an initiating factor in this process. PMID- 1742426 TI - An evolutionarily-conserved role for murine Ly-1 B cells in protection against bacterial infections. AB - The murine Ly-1 B cell lineage, although comprising only a minority of peripheral IgM+ B cells, secretes a major proportion of the IgM antibodies occurring naturally in serum. Ly-1 B cells also seed a large number of IgA+ plasma cells to the gut walls, thereby contributing significantly to production of natural IgA antibodies in response to chronic stimulation by the normal gut flora. Apart from these naturally-produced antibodies, Ly-1 B cells also produce specific antibodies following deliberate immunisation with the bacterial cell wall antigens, phosphorylcholine and dextran. The inability of the X-linked immunodeficient CBA/N mice to produce antibody responses to these two antigens is overcome by reconstitution with normal Ly-1 B cells from the parental CBA strain. Ly-1 B cells therefore appear to play a dominant role in natural immunity and protection against bacterial infections. The compartmentalisation of development and function within murine B cells is suggestive of an evolutionary structuring of the murine immune system, with Ly-1 B cells representing a conserved, primitive B cell lineage and retaining key, associated functions. PMID- 1742427 TI - Modelling adolescent blood pressure patterns and their prediction of adult pressures. AB - Tracking of blood pressure in adolescent boys is investigated using a mathematical model that corresponds to progression along a constant percentile. A more general analysis, based on the method of principal components, is also proposed that determines various alternative tracks or patterns that are most prevalent in the longitudinal blood pressure data. The degree of tracking along a constant percentile curve for systolic pressure was moderately high, as evidenced by a tracking index of .78 explaining 81% of the variance, but less strong for diastolic (tracking index of .60) where tracking along a percentile explained 66% of the variance. The value of the more general analysis of blood pressure patterns may lie in the assessment of adolescent risk factors for elevated adult blood pressure. Using adolescent patterns determined by either statistical model, adult systolic at age 38 was predicted (R2 = .22) by the concept of a systolic fixed percentile curve in adolescence, and similarly for diastolic (R2 = .21). However, the more general analysis based on longitudinal principal components further suggests that boys who have a larger than usual systolic peak at age 14 years, which is near the time of the adolescent physical growth spurt in these boys, may be more likely to have higher systolic pressures at age 38. Because the adult data were incomplete and highly unbalanced, these findings were obtained using random-effects models for longitudinal data. PMID- 1742428 TI - A clonal selection based timecourse model for antibody responses to killed vaccine, with applications to foot and mouth disease. AB - Published models for the timecourse of the immune response are reviewed for their applicability to data from animals that have been injected with killed vaccine. Simple models are required so that statistical fitting procedures become straightforward. A class of models that incorporates the concept of clonal selection has been found useful. Immune memory is described in terms of persistence of mean antibody affinity when the overall concentration of antibody has declined towards background. The model is demonstrated on multipoint affinity distributions and initial negative exponential densities, from which conditions for boundedness can be developed. Predictions are made that are consistent with experiments on the evolution of immunoassay data using foot and mouth disease vaccine. PMID- 1742429 TI - Analysis of trinomial responses from reproductive and developmental toxicity experiments. AB - This paper presents a Dirichlet-trinomial distribution for modelling data obtained from reproductive and developmental studies. The common endpoints for the evaluation of reproductive and developmental toxic effects are the number of dead fetuses, the number of malformed fetuses, and the number of normal fetuses for each litter. With current statistical methods for the evaluation of reproductive and developmental effects, the effect on the number of deaths and the effect on the number of malformations are analyzed separately. The Dirichlet trinomial model provides a procedure for the analysis of multiple endpoints simultaneously. This proposed Dirichlet-trinomial model is a generalization of the beta-binomial model that has been used for handling the litter effect in reproductive and developmental experiments. Likelihood ratio tests for differences in the number of deaths, the number of malformations, and the number of normals among dosed and control groups are derived. The proposed test procedure based on the Dirichlet-trinomial model is compared with that based on the beta-binomial model with an application to a real data set. PMID- 1742430 TI - Pooling data for stability studies: testing the equality of batch degradation slopes. AB - Pharmaceutical products are routinely monitored for their stability over time. Stability studies generally consist of a random sample of dosage units (e.g., tablets, capsules, vials) from a batch or several batches placed in a storage room and periodically assayed for their drug content. The degradation of the drug product is modeled, and according to the Guideline for Submitting Documentation for Stability Studies of Human Drugs and Biologics (Food and Drug Administration, 1987), the shelf-life is calculated as the time point at which the lower 95% confidence limit about the fitted regression line crosses the lowest acceptable limit for drug content (frequently 90% of the labeled amount). When multiple batches are manufactured, preliminary testing for any batch differences (both slope and intercept) should precede pooling stability data from all batches in the analysis. The Guideline recommends a level of significance of .25 for such preliminary testing based on the work described by Bancroft (1964, Biometrics 20, 427-442). Using such a large significance level helps ensure that the power of the test for the batch differences is sufficiently high. This paper presents an approach whereby the power of the test is fixed and the significance level of the test needed to obtain this power is calculated from the data. If the observed significance level does not achieve the calculated significance level, then the data can be pooled. Examples will illustrate the relative performance of the FDA guideline and the proposed procedure. PMID- 1742431 TI - Estimating drug shelf-life with random batches. AB - The problem of assessing the shelf-lives of drug products in the market is considered. We focus on the situation where the drug characteristic of interest has a linear relationship over time and batch-to-batch variation is present. Two methods for assessing shelf-lives are proposed based on the weighted least squares method under a regression model with random coefficients. An application to some stability data from the pharmaceutical industry is presented. PMID- 1742432 TI - A numerical solution to the equilibria of the two-locus two-allele selection model. AB - Examination of the equilibria of the standard two-locus two-allele selection model leads to the construction of a polynomial with coefficients derived from selective values in the genotypic fitness matrix. This polynomial can be partially factored algebraically and numerical techniques are available to extract the roots of the remainder. Each root provides a possible value of the disequilibrium coefficient and the gametic frequencies at equilibrium, and these can be readily checked for stability. PMID- 1742433 TI - Residual plots for log odds ratio regression models. AB - This article describes graphical diagnostic methods for log odds ratio regression models. To study the effects of an additional covariate on log odds ratio regression analysis, three types of residual plots based on weighted least squares (WLS) are discussed: (i) added variable plot (partial regression plot), (ii) partial residual plot, and (iii) augmented partial residual plot. These plots provide diagnostic procedures for identifying heterogeneity of error variances, outliers, or nonlinearity of the model. They are especially useful for clarifying whether including a covariate as a linear term is appropriate, or whether quadratic or other nonlinear transformations are preferable. A well-known data set for case-control studies is analyzed to illustrate the residual plots. PMID- 1742434 TI - A nonparametric estimator of the shift effect for repeated observations. AB - In a nonparametric two-sample model for independent observations with repeated measurements, a new point estimator and a new distribution-free confidence interval for the difference in means are introduced. The method is based on some ideas in Hodges and Lehmann (1963, Annals of Mathematical Statistics 34, 598 611). The asymptotic theory in Brunner and Neumann (1983, Biometrical Journal 24, 373-389; 1986; Biometrical Journal 28, 394-402) and the results for small sample sizes in Brunner and Compagnone (1988, Statistical Software Newsletter 14, 36-42) are used. The new estimators are applied to a problem in morphometry. PMID- 1742435 TI - Second-order analysis of spatial clustering for inhomogeneous populations. AB - Motivated by recent interest in the possible spatial clustering of rare diseases, the paper develops an approach to the assessment of spatial clustering based on the second-moment properties of a labelled point process. The concept of no spatial clustering is identified with the hypothesis that in a realisation of a stationary spatial point process consisting of events of two qualitatively different types, the type 1 events are a random sample from the superposition of type 1 and type 2 events. A diagnostic plot for estimating the nature and physical scale of clustering effects is proposed. The availability of Monte Carlo tests of significance is noted. An application to published data on the spatial distribution of childhood leukaemia and lymphoma in North Humberside is described. PMID- 1742436 TI - Elementary methods of cohort analysis with several exposure levels. AB - This paper proposes an extension of the Mantel-Haenszel rate ratio for the dichotomous exposure to the multiple exposure levels. This extension is based on the unbiased estimating function approach and yields closed-form Mantel-Haenszel rate ratio estimators. Dually consistent variance and covariance estimators of the estimating functions are given and a quasi-score-based confidence interval for individual common rate ratio is provided. A similar extension to the common rate difference case is also given. PMID- 1742438 TI - Validation samples. PMID- 1742437 TI - Algorithms versus models for analyzing data that contain misclassification errors. AB - Espeland and Hui (1987, Biometrics 43, 1001-1012) propose a methodology for analysing epidemiologic data contaminated by misclassification. They explicate their algorithm by a data set concerning cervical cancer and circumcision. We reanalyse these data using a conditional independence assumption different from theirs, and reach radically different conclusions. Espeland and Hui's methodology is a form of correlation analysis. We propose an alternative methodology based on the logic of regression analysis. PMID- 1742439 TI - Fraudulent statistical methods. PMID- 1742440 TI - A comparison of several point estimators of the odds ratio in a single 2 x 2 contingency table. AB - The relative performance of the unconditioned maximum likelihood estimators (UMLEs), conditional MLEs (CMLEs), and Jewell-type estimators of the odds ratio (OR) and its logarithm were investigated in sets of single 2 x 2 contingency tables. The tables were generated by complete enumeration of all possible cell frequencies consistent with a single fixed margin. The bias, mean squared error (MSE), and average absolute error (AAE) were computed for all estimators using the individual table probabilities as weights. The results showed that, for the OR, Jewell's estimator usually had smaller bias, MSE, and AAE than either of the MLEs. While the differences were often slight for MSE and AAE, for bias it was sometimes substantial. For the log(OR), the UMLE usually had the lowest bias, and its MSE and AAE were only slightly greater than those for the other estimators. Overall, we recommend estimation on the log scale using the UMLE. If OR is to be estimated, Jewell's method had strong merit, although it is nonsymmetric with respect to the table orientation. In view of this, the UMLE may again be favoured in some situations. PMID- 1742441 TI - Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses. AB - Generalized estimating equations are introduced in an ad hoc fashion for the covariance matrix of a multivariate response. These equations are to be solved jointly with score equations from a generalized linear model for mean parameters. A class of quadratic exponential models is used to develop joint estimating equations for mean and covariance parameters in a more systematic fashion, and proposals for the use of such equations are developed. Comments on the relative merits of the ad hoc and model-based approaches to estimation are given and a regression illustration with a bivariate response is provided. PMID- 1742442 TI - Diagnostic plots in Cox's regression model. AB - Two diagnostic plots are presented for validating the fitting of a Cox proportional hazards model. The added variable plot is developed to assess the effect of adding a covariate to the model. The constructed variable plot is applied to detect nonlinearity of a fitted covariate. Both plots are also useful for identifying influential observations on the issues of interest. The methods are illustrated on examples of multiple myeloma and lung cancer data. PMID- 1742443 TI - Bayesian subset analysis. AB - As a means of assessing the importance of variation in treatment effect among patient subsets, we derived posterior distributions for subset-specific treatment effects. The effects are represented by combinations of terms for treatment and treatment-by-covariate interaction effects in familiar regression models. Exchange-ability among the interactions is a key assumption; thus, the results are of interest primarily in the context of examining a collection of subsets with no definite a priori distinction relative to treatment effect. Exchangeability leads to a shrinking of the posterior distributions of the interaction terms toward the natural origin of 0, offsetting the tendency of the estimated effects to disperse. The method is applied to parameter estimates from a proportional hazards regression analysis of survival data from a clinical trial, invoking the approximate multivariate normal distribution of the estimates. No subjective prior distributions are required. Vague priors are used for all of the regression coefficients except the treatment-by-covariate interactions, which are assumed to follow a normal distribution. PMID- 1742444 TI - Fitting mixture models to birth weight data: a case study. AB - Birth weights by gestational age are compared in two birth cohorts from Northern Finland, the first from 1966 and the second from 1985-1986. A curious fact in the data is that mean birth weight before the 39th week was lower in the latter series although the mean birth weight for the total series was higher. Similar findings have been reported in other series. A mixture model with the nonparametric regression function is proposed for studying the hypothesis that the difference was caused by more frequent gross errors in gestational assessment in the earlier cohort. The probability of an error in gestational assessment then greatly depends on the observed gestational age, which makes the mixture model nonstandard. Maximum likelihood solutions to the parameters in the proposed model were computed employing the general expectation-maximization (EM) algorithm. A technique for studying the effect of errors on the intrauterine weight gain curve is proposed and applied to our two birth cohorts. The risk of underestimation of gestational age seems to be larger in the previous series and the differences between the growth curves almost totally vanish when "corrected" by means of the mixture model. PMID- 1742445 TI - A model for incorporating historical controls into a meta-analysis. AB - A method is presented for estimating the treatment effect in a meta-analysis when some of the studies are comparative studies, and the rest are noncomparative, historical control studies. A random-effects model is used in which the baseline effect in each study is random, but the treatment effect is constant. With this model the appropriate contribution of the historical studies can be determined. Extensions of the model are developed to accommodate preliminary tests for bias, and for the possibility that the treatment effect is heterogeneous. PMID- 1742446 TI - The design of a panel study under an alternating Poisson process assumption. AB - We discuss the design of a panel study for the estimation of the average durations in the two states of an alternating Poisson process. Two types of designs are examined. The first fixes the number of follow-up waves but permits the total length of follow-up to vary, and the second varies the number of follow up waves with fixed length. Simple expressions for nearly optimal designs are presented, and we compare these with designs allowing for continuous observation. Both equilibrium and nonequilibrium cases are examined. An example is given using morbidity data to illustrate how these results can be applied. PMID- 1742447 TI - Modelling the influence of risk factors on familial aggregation of disease. AB - One often observes a familial resemblance of risk factors of disease. The following question then arises: How much familial aggregation of cases of disease would be expected because of this resemblance? This problem is attacked through a particular model where the risk is supposed to depend exponentially on the risk factors. Only pairs of relatives (father/son) are considered. The calculations are performed both with normally distributed risk factors and with particular skewed distributions. An application to coronary heart disease is given. PMID- 1742448 TI - Nonparametric estimation of the incubation period of AIDS based on a prevalent cohort with unknown infection times. AB - Estimation of the incubation period distribution of human immunodeficiency virus based on prevalent cohorts of subjects, already infected at the time of recruitment, is complicated by the absence of information on the original times of infection. Here, we overcome this difficulty by using a prior distribution for the infection times, based on external data. Our estimate is nonparametric, but uses smoothness assumptions to avoid instability. The method is illustrated on two prevalent cohorts from San Francisco, separately and combined. The estimates produced agree with other published estimates of the incubation period distribution. PMID- 1742449 TI - A generalized stochastic model for the analysis of infectious disease final size data. AB - A stochastic infectious disease model was developed by Ball (1986, Advances in Applied Probability 18, 289-310) in which the distribution of the length of the infectious period is allowed to have any distribution that can be described by its Laplace transform. We extend this model such that the infection can be transmitted within the population or from an unspecified source outside the population. Also, discrete heterogeneity in the population can be modeled to incorporate variable susceptibility, variable infectivity, and/or mixing behaviors. The model is fitted to serologic data from two influenza epidemics in Tecumseh, Michigan, using maximum likelihood estimation procedures. The estimates show a clustering pattern by age groups. PMID- 1742450 TI - An adaptive weighted log-rank test with application to cancer prevention and screening trials. AB - A class of adaptive weighted log-rank statistics is described where the vector of weights is chosen in a data-dependent way from a family of "smooth" weight vectors. A parametric family of weight vectors is identified which includes most shapes of weighting vectors that will be near optimal in many cancer prevention and screening trials. This family of weight vectors is used in an application of the proposed method to data from a breast cancer screening trial. Results from a small simulation study comparing the power of the adaptive statistic to that of the unweighted log-rank statistic are presented. PMID- 1742451 TI - Nonparametric estimation of the size-metastasis relationship in solid cancers. AB - This paper is concerned with the relationship between the occurrence of metastases and the size of primary cancers. We consider two probabilistic characterizations of this relationship. First is the distribution function of tumor sizes at the point of metastatic transition; second is the probability that detectable metastases are present when the cancer comes to medical attention. The equation relating these two functions is developed and conditions for their being identical are explored. Since the tumor size at the point of metastasis is not usually observable, estimation of the first distribution requires the use of the EM algorithm. Nonparametric methods of estimating both functions are explored, with attention to the fact that tumors often fail to be measured, particularly those that are known to be metastatic. The methods are applied to the estimation of primary tumor size at the point of distant metastasis in lung cancer (epidermoid and adenocarcinoma) and colorectal cancer and at the point of nodal metastasis in breast cancer. Monte Carlo experiments confirm that the bias inherent in the methodology is acceptably small. PMID- 1742452 TI - Coupling of ferric iron spin and allosteric equilibrium in hemoglobin. AB - The allosteric transition in triply ferric hemoglobin has been studied with different ferric ligands. This valency hybrid permits observation of oxygen or CO binding properties to the single ferrous subunit, whereas the liganded state of the other three ferric subunits can be varied. The ferric hemoglobin (Hb) tetramer in the absence of effectors is generally in the high oxygen affinity (R) state; addition of inositol hexaphosphate induces a transition towards the deoxy (T) conformation. The fraction of T-state formed depends on the ferric ligand and is correlated with the spin state of the ferric iron complexes. High-spin ferric ligands such as water or fluoride show the most T-state, whereas low-spin ligands such as cyanide show the least. The oxygen equilibrium data and kinetics of CO recombination indicate that the allosteric equilibrium can be treated in a fashion analogous to the two-state model. The binding of a low-spin ferric ligand induces a change in the allosteric equilibrium towards the R-state by about a factor of 150 (at pH 6.5), similar to that of the ferrous ligands oxygen or CO; however, each high-spin ferric ligand induces a T to R shift by a factor of 40. PMID- 1742453 TI - Linear nonequilibrium thermodynamics describes the dynamics of an autocatalytic system. AB - A model simulating oscillations in glycolysis was formulated in terms of nonequilibrium thermodynamics. In the kinetic rate equations every metabolite concentration was replaced with an exponential function of its chemical potential. This led to nonlinear relations between rates and chemical potentials. Each chemical potential was then expanded around its steady-state value as a Taylor series. The linear (first order) term of the Taylor series sufficed to simulate the dynamic behavior of the system, including the damped and even sustained oscillations at low substrate input or high free-energy load. The glycolytic system is autocatalytic in the first half. Because oscillations were obtained only in the presence of that autocatalytic feed-back loop we conclude that this type of kinetic nonlinearity was sufficient to account for the oscillatory behavior. The matrix of phenomenological coefficients of the system is nonsymmetric. Our results indicate that this is the symmetry property and not the linearity of the flow-force relations in the near equilibrium domain that precludes oscillations. Given autocatalytic properties, a system exhibiting liner flow-force relations and being outside the near equilibrium domain may show bifurcations, leading to self-organized behavior. PMID- 1742454 TI - X-ray studies of order-disorder transitions in the myosin heads of skinned rabbit psoas muscles. AB - Using x-rays from a laboratory source and an area detector, myosin layer lines and the diffuse scattering between them in the moderate angle region have been recorded. At full overlap, incubation of rigor muscles with S-1 greatly reduces the diffuse scattering. Also, three of the four actin-based layer lines lying close to the meridian (Huxley, H. E., and W. Brown, 1967. J. Mol. Biol. 30:384 434; Haselgrove, J. C. 1975. J. Mol. Biol. 92:113-143) increase, suggesting fuller labeling of the actin filaments. These results are consistent with the idea (Poulsen, F. R., and J. Lowy, 1983. Nature [Lond.]. 303:146-152) that some of the diffuse scattering in rigor muscles is due to a random mixture of actin monomers with and without attached myosin heads (substitution disorder). In relaxed muscles, regardless of overlap, lowering the temperature from 24 to 4 degrees C practically abolishes the myosin layer lines (a result first obtained by Wray, J.S. 1987. J. Muscle Res. Cell Motil. 8:62 (a). Abstr.), whilst the diffuse scattering between these layer lines increases appreciably. Similar changes occur in the passage from rest to peak tetanic tension in live frog muscle (Lowy, J., and F.R. Poulsen. 1990. Biophys. J. 57:977-985). Cooling the psoas demonstrates that the intensity relation between the layer lines and the diffuse scattering is of an inverse nature, and that the transition occurs over a narrow temperature range (12-14 degrees C) with a sigmoidal function. From these results it would appear that the helical arrangement of the myosin heads is very temperature sensitive, and that the disordering effect does not depend on the presence of actin. Measurements along the meridian reveal that the intensity of the diffuse scattering increases relatively little and does so in a nearly linear manner: evidently the axial order of the myosin heads is much less temperature sensitive. The combined data support the view (Poulsen, F. R., and J. Lowy. 1983. Nature [Lond.]. 303:146-152) that in relaxed muscles a significant part of the diffuse scattering originates from disordered myosin heads. The observation that the extent of the diffuse scattering is greater in the equatorial than in the meridional direction suggests that the disordered myosin heads have an orientation which is on average more parallel to the filament axis. PMID- 1742455 TI - Shape transitions and shape stability of giant phospholipid vesicles in pure water induced by area-to-volume changes. AB - Shape transformations of vesicles of dimyristoylphosphatidylcholine (= DMPC) and palmitoyloleylphosphatidylcholine (= POPC) in ion-free water were induced by changing the area-to-volume ratio via temperature variations. Depending on the pretreatment we find several types of shape changes for DMPC (in pure water) at increasing area-to-volume ratio: (a) budding transitions leading to the formation of a chain of vesicles at further increase of the area-to-volume ratio, (b) discocyte-stomatocyte transitions, (c) reentrant dumbbell-pear-dumbbell transitions, and (d) spontaneous blebbing and/or tether formation of spherical vesicles. Beside these transitions a more exotic dumbbell-discocyte transition (e) was found which proceeded via local instabilities. Pears, discocytes, and stomatocytes are stable with respect to small temperature variations unless the excess area is close to values corresponding to limiting shapes of budded vesicles where temperature variations of less than or equal to 0.1 degree C lead to spontaneous budding to the inside or the outside. For POPC we observed only budding transitions to the inside leading either to chains of vesicles or to distributions of equally sized daughter vesicles protruding to the inside of the vesicle. Preliminary experiments concerning the effect of solutes are also reported. The first three types of shape transitions can be explained in terms of the bilayer coupling model assuming small differences in thermal expansivities of the two monolayers. This does not hold for the observed instabilities close to the limiting shapes. PMID- 1742456 TI - Time-dependent recovery of passive neutrophils after large deformation. AB - Experiments are performed in which a passive human neutrophil is deformed into an elongated "sausage" shape by aspirating it into a small glass pipette. When expelled from the pipette the neutrophil recovers its natural spherical shape in approximately 1 minute. This recovery process is analyzed according to a Newtonian, liquid-drop model in which a variational method is used to simultaneously solve the hydrodynamic equations for low Reynolds-number flow and the equations for membrane equilibrium with a constant membrane tension. The theoretical model gives a good fit to the experimental data for a ratio of membrane cortical tension to cytoplasmic viscosity of approximately 1.7 x 10(-5) cm/s (0.17 micron/s). However, when the cell is held in the pipette for only a short time period of 5 s or less, and then expelled, the cell undergoes an initial, rapid elastic rebound suggesting that the cell behaves in this instance as a Maxwell viscoelastic liquid rather than a Newtonian liquid with constant cortical tension. PMID- 1742457 TI - Picosecond study of the near infrared absorption band of hemoglobin after photolysis of carbonmonoxyhemoglobin. AB - Picosecond absorption spectroscopy is used to examine the position and band shape of the near infrared absorption band of hemoglobin as a function of time after the photodissociation of CO from carbonmonoxyhemoglobin. For the earliest delay time probed, 35 ps, the peak of the transient spectrum is at 765 nm, red shifted by 6 nm from that characteristic of equilibrium deoxyhemoglobin. No evolution in either the peak position or band shape is observed for time delays up to 60 ns. In addition, the position and shape of the spectrum are independent of photolysis energies ranging from 15 microJ/pulse to 150 microJ/pulse, spanning conditions under which the photon/heme ratio is varied from 0.01 to 2.0. This indicates that the geometry in the heme group is unrelaxed and that equilibration of the surrounding protein structure occurs on a time scale longer than 60 ns. PMID- 1742458 TI - Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. AB - Analysis of the trajectories of small particles at high spatial and temporal resolution using video enhanced contrast microscopy provides a powerful approach to characterizing the mechanisms of particle motion in living cells and in other systems. We present here the theoretical basis for the analysis of these trajectories for particles undergoing random diffusion and/or systematic transport at uniform velocity in two-dimensional systems. The single particle tracking method, based on observations of the trajectories of individual particles, is compared with methods that characterize the motions of a large collection of particles such as fluorescence photobleaching recovery. Determination of diffusion coefficients or transport velocities either from correlation of positions or of velocities of the particles is discussed. A result of practical importance is an analysis of the dependence of the expected statistical uncertainty of these determinations on the number of position measurements. This provides a way of judging the accuracy of the diffusion coefficients and transport velocities obtained using this approach. PMID- 1742459 TI - Orientation of melittin in phospholipid bilayers. A polarized attenuated total reflection infrared study. AB - The helical order parameter of the 26-residue amphiphilic bee venom peptide melittin was measured by polarized attenuated total reflection infrared spectroscopy (ATR-IR) in dry phospholipid multibilayers (MBLs) and when bound to single supported planar bilayers (SPBs) under D2O. Melittin adopted an alpha helical conformation in MBLs of dipalmitoyl-phosphatidylcholine (DPPC), 1 palmitoyl-2-oleoyl-phosphatidylcholine (POPC), a 4:1 mixture of POPC and 1 palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), and when bound to SPBs of POPC:POPG (4:1). The order parameter of the alpha-helix in the bilayers depended mainly on the type of membrane preparation, and only little on the phospholipid composition of the bilayers. On hydrated SPBs, the helical order parameter was negative, indicating that the alpha-helix long axis of melittin was preferentially oriented parallel to the plane of the supported membrane. However, in dry MBLs, the helical order parameter was positive, indicating that the alpha helix of melittin was preferentially oriented parallel to the phospholipid fatty acyl chains. It is concluded that the orientation of melittin in membranes depends on the degree of hydration of the model membranes rather than on the technique which is used for its determination. ATR-IR spectroscopy of polypeptides in or associated with supported planar membranes in D2O may become a useful tool for the determination of their orientation in and on membranes. PMID- 1742460 TI - Ba2+ release from soda glass modifies single maxi K+ channel activity in patch clamp experiments. AB - Glasses used to fabricate patch pipettes may release components which affect ion channels (Cota, G., and C.M. Armstrong. 1988. Biophys. J. 53:107-109; Furman, R.E., and J.C. Tanaka. 1988. Biophys. J. 53:287-292; Rojas, L., and C. Zuazaga. 1988. Neurosci. Lett. 88:39-44). The gating properties of maxi K+ channels from Necturus gallbladder epithelium depend on whether borosilicate glass (BG) or blue tip hematocrit glass (SG) is used to construct the patch pipettes. The data are consistent with solubilization from SG of a component which exerts voltage dependent, cytosolic-side specific block, closely resembling "slow block" by Ba2+ ions. Ringer's solution preincubated with SG, but not with BG, blocked inside-out maxi K+ channels when used as bathing solution. Mass spectrometry revealed that Ba2+ is released by the glass from fast and slow-release compartments (SG contains 3% wt/wt BaO), and is the only ion found in the solution at concentrations consistent with the observed channel block. Additionally, SG released O2-, Na+, Ca2+, and Mg2+, all to micromolar concentrations. These elements do not interfere with maxi K+ channels but they could in principle alter the properties of other ion channels. Thus, screening for channel-modifying substances released by the glass may be necessary for the adequate interpretation of patch-clamp results. PMID- 1742461 TI - Membrane binding induces lipid-specific changes in the denaturation profile of bovine prothrombin. A scanning calorimetry study. AB - Prothrombin denaturation was examined in the presence of Na2EDTA, 5mM CaCl2, and CaCl2 plus membranes containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) in combination with either bovine brain phosphatidylserine (PS) or 1,2 dioleoyl-phosphatidylglycerol (DOPG). Heating denaturation of prothrombin produced thermograms showing two peaks, a minor one at approximately 59 degrees C previously reported to correspond to denaturation of the fragment 1 region (Ploplis, V. A., D. K. Strickland, and F. J. Castellino 1981. Biochemistry. 20:15 21), and a main one at approximately 57-58 degrees C, reportedly due to denaturation of the rest of the molecule (prethrombin 1). The main peak was insensitive to the presence of 5mM Ca2+ whereas the minor peak was shifted to higher temperature (Tm approximately 65 degrees C) by Ca2+. Sufficient concentrations of POPC/bovPS (75/25) large unilamellar vesicles to guarantee binding of 95% of prothrombin resulted in an enthalpy loss in the main endotherm and a comparable enthalpy gain in the minor endotherm accompanying an upward shift in peak temperature (Tm approximately 73 degrees C). Peak deconvolution analysis on the prothrombin denaturation profile and comparison with isolated prothrombin fragment 1 denaturation endotherms suggested that the change caused by POPC/PS vesicles reflected a shift of a portion of the enthalpy of the prethrombin 1 domain to higher temperature (Tm approximately 77 degrees C). The enthalpy associated with this high-temperature endotherm increased in proportion to the surface concentration of PS. By contrast, POPC/DOPG (50/50) membranes shifted the prethrombin 1 peak by 4 degrees C to a lower temperature and the fragment 1 peak by 5 degrees C to a higher temperature. The data lead to a hypothesis that the fragment 1 and prethrombin 1 domains of prothrombin do not denature quite independently and that binding of prothrombin to acidic-lipid membranes disrupts the interaction between these domains. It is further hypothesized that PS containing membranes exert the additional specific effect of decoupling the denaturation of two subdomains of the prethrombin 1 domain of prothrombin. PMID- 1742462 TI - Electrolyte effects on bilayer tubule formation by a diacetylenic phospholipid. AB - A general effect by dissolved electrolytes to destabilize the curvature of bilayer tubules prepared from the diacetylenic phospholipid, 1,2-bis(10,12 tricosadiynoyl)-sn-glycero-3-phosphocholine is not found. This observation discounts the role of an electrostatic interaction between polarization charges on the edges of a ferroelectric bilayer as a means by which the cylindrical curvature may be stabilized in these structures (de Gennes, P. G. 1987. C. R. Acad. Sci. Paris. 304:259-263). The solution-mediated ionic interactions of electrolytes with this phospholipid appear not to influence significantly the relative stability of the crystalline state of the tubule, but at high levels of a few salts, may affect the nucleation and growth of the crystalline bilayer. Curvature of the bilayer in these tubular structures apparently derives from an interaction that is not very sensitive to the presence of electrolytes. Cylindrical curvature may alternatively arise from a bending force within the bilayer that is intrinsic to the anisotropic packing of the lipid molecules (Helfrich, W., and J. Prost. 1988. Phys. Rev. A38:3065-3068; Chappell, J. S., and P. Yager. 1991. Chem. Phys. Lipids. In press), and may therefore be largely determined by the packing interactions within the hydrophobic region of the tubular bilayer. PMID- 1742463 TI - Mass-weighted molecular dynamics simulation of the protein-ligand complex of rhizopuspepsin and inhibitor. AB - The mass-weighted molecular dynamics simulation method was developed previously for sampling the multidimensional conformational space of linear and cyclic polypeptides and studying their conformational flexibility. Herein results from molecular dynamics simulations of the protein-ligand complex of the aspartyl protease rhizopuspepsin and a polypeptide inhibitor are reported. The dihedral conformational space sampling for the linear peptide inhibitor in situ was found to be increased in the mass-weighted simulation as in other molecular systems previously studied. More significantly, the physical space of the enzyme binding pocket was also sampled efficiently in the simulations and multiple binding sites were identified for the inhibitor. These results suggest that it may be possible now to study, by computer simulations, the putative initial enzyme-inhibitor complex suggested experimentally from the time-dependent kinetics of enzyme inhibition by slow-binding inhibitors (Morrison, J. F., and C. T. Walsh. 1988. Adv. Enzymol. 61:201), and/or conformational substates in protein-ligand complexes suggested in the study of reassociation dynamics of myoglobin and carbon monoxide following photolysis (Austin, R. H., K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. Gunsalus. 1975. Biochemistry. 14:5355). Moreover, the intermediate binding steps and the molecular flexibility of the inhibitor shown in the MWMD simulation may have crucial roles in the ligand binding process. PMID- 1742464 TI - Heart rate and hemodynamics. AB - Evidence is presented to show that cardiac output is little affected by changes in heart rate but the heart volumes, systolic and diastolic, are inversely related. Heart rate is controlled by changes in efferent nerves, sympathetic and vagal, which are in turn controlled from central and reflex sources. An argument is presented showing that reflexes from receptors in the atria control heart volumes by affecting, in the short term heart rate, and in the long term water intake (thirst) and urine flow, and therefore blood volume. Explanations of the mechanisms involved are presented. PMID- 1742465 TI - Coronary response to transient increases in transmural pressure. AB - Previous studies have shown that transient increases in aortic blood pressure obtained by occlusion of the descending thoracic aorta, in anesthetized dogs with beta-blockade and vagal section, did not affect coronary vascular resistance apart from a non-significant increase just after release of the constriction. The present study examined whether this response also occurred in the normally innervated heart. Experiments were carried out in six anesthetized dogs, in which pressure in the aortic root and in the left ventricle, as well as flow in the left circumflex coronary artery, were recorded. Coronary vascular resistance was calculated as the ratio of the difference between aortic pressure and left ventricular pressure to coronary circumflex flow during the slow inflow phase. Before occlusion coronary vascular resistance was significantly lower than during the same period in the previous studies using animals with beta-blockade and vagal section. During the occlusion, in contrast with the previous investigation, the increase in aortic pressure caused a significant increase in coronary vascular resistance 10 seconds after the beginning of the occlusion. Coronary vascular resistance was further increased immediately after release of the occlusion, concomitantly with the decrease in aortic pressure, which fell abruptly below the control level. The increase immediately after the release of the constriction was qualitatively similar, but greater in extent, to that observed in the animals with vagal section and beta-blockade. These differences are assumed to depend on a lower vasomotor tone in the normally innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742466 TI - The effects of thyroid state on sarcomere dynamics of ventricular cells and contraction of papillary muscles in the rat heart. AB - Diastolic sarcomere length, amplitude of maximal sarcomere shortening, maximal rate of sarcomere shortening, maximal rate of sarcomere re-lengthening, time to peak sarcomere shortening and trans-sarcolemmal ion currents were measured in isolated ventricular cells from euthyroid, hypothyroid and hyperthyroid rats. The data were compared with the developed tension and time to peak tension of papillary muscles. The diastolic sarcomere length was not affected by the changes in thyroid state. Hypothyroidism led to an increased time to peak sarcomere shortening, an increased time to peak tension of the papillary muscle, and a depression of the maximal rates of shortening and elongation of the sarcomeres. Changes in dynamics of the sarcomere and contraction of papillary muscle did not occur in parallel under the influence of hyperthyroidism. In comparison with the euthyroid state, the time to peak tension was shortened and amplitude of shortening of the sarcomere was increased. The time to peak shortening of the sarcomere and developed tension of papillary muscle remained unaltered. In cardiac cells, hypothyroidism was associated with a decreased slow Ca2+ current and hyperthyroidism with an increased slow Ca2+ current. In contrast to euthyroid and hypothyroid cardiac cells, the hyperthyroid cardiomyocytes exhibited a trans sarcolemmal transient inward current after repolarization. Both hypothyroidism and hyperthyroidism resulted in a depressed potentiation of sarcomere shortening and myocardial developed tension after resting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742467 TI - A mathematical model of the flow of blood through the left coronary artery. AB - Several models of the coronary circulation have been proposed, relating arterial flow waveform and cardiac contraction. Some of them have produced new concepts, such as back pressure, and zero flow pressure, founded on an over-simplified description of vascular collapse. Experimental studies have shown that the actual dynamics of a collapsible tube cannot be adequately described using a lumped parameter model. A distributed parameter model is therefore proposed and compared with the previous models. PMID- 1742468 TI - Group I fibers: pressor reflex and cardiac activity. AB - Experiments were performed on cats to see whether stimulation of group I afferent fibers from gastrocnemius-soleus muscles induced changes in cardiac activity, in addition to the increase in systemic arterial pressure already established. The results show that the increase in arterial pressure is accompanied by an increase in systolic left ventricular pressure, without any significant changes in cardiac inotropism and chronotropism. It is concluded that the cardiac innervation is not an important efferent pathway of the pressor reflex evoked by stimulating group I afferent fibers, and that the reflex increase in arterial pressure depends mainly on an increase in peripheral vascular resistance. PMID- 1742469 TI - Activation energy of the cardiac Na+/Ca2+ exchanger in sarcolemmal vesicles and reconstituted proteoliposomes. AB - Sarcolemmal membrane vesicles isolated from bovine ventricular tissue accumulate Ca2+ through the Na+/Ca2+ exchanger when exposed to an outwardly directed Na+ gradient. This Ca2+ is then released by the same mechanism if the vesicles are transferred to a Ca(2+)-depleted Na+ buffer. Using the Ca+ indicator, arsenazo III, and a stopped-flow spectrophotometer, we can directly follow the kinetics of Ca2+ extrusion. We can thus measure the activity of the Na+/Ca2+ exchanger by the initial rate of Ca2+ release. We found that it depends upon the external Na+ concentration in a cooperative way, with a Hill coefficient of 2. By studying the temperature dependence of Na+/Ca2+ exchange, we found that it can be described by a single activation energy: Ea = 8.3 +/- 0.4 Kcal/mol. When the Na+/Ca2+ exchanger is reconstituted into lipid vesicles of defined composition, we observe a higher activity if cholesterol is among the lipids. The activation energy becomes 6.1 +/- 0.1 Kcal/mol in this system, but the Arrhenius plot shows a decreased slope for temperatures above 33 degrees C. PMID- 1742470 TI - Capacity of making choices in the brain and its quantitative evaluation: an application to comprehension of incomplete sentences and semantic commitments. AB - The natural language processor in the brain generates information when it disambiguates words while reading a text in which information generation refers to making semantic commitments. Contextual facilitation of disambiguation of words appearing in the perturbed text that is derived from the unperturbed and natural one by deleting words randomly, lets the language processor revise the previous semantic commitments continuously. As the frequency of revising the previous semantic commitments increases, the amount of information generated by the language processor also increases. Revising previous semantic commitments in a continuous fashion is the functional property intrinsic to the language processor in the brain. PMID- 1742471 TI - Directionality of evolution at molecular and organismic levels. AB - The molecular evolution theories of Eigen and Kimura are compared and their difference is explained. In terms of Eigen's theory for the evolution of macromolecules, the selection of genotypes occurs directly. The physical meaning of the neutral theory is the degeneracy of the correlation between a phenotype and a genotype at the molecular level. A model theory of evolution on a fitness landscape is proposed. The theory shows that the constraints of selection determined by the structure and dynamics of previous evolution stages increases its rate strongly. PMID- 1742472 TI - Self-reproducing systems: structure, niche relations and evolution. AB - A formal definition of a self-reproducing system is proposed using Petri nets. A potential self-reproducing system is a set of places in the Petri net such that the number of tokens in each place increases due to some sequence of internal transitions (a transition is called internal to the marked subset of places if at least one of its starting places and one of its terminating places belongs to that subset). An actual self-reproducing system is a system that compensates the outflow of its components by reproduction. In a suitable environment every potential self-reproducing system becomes an actual one. Each Petri net can be considered as an ecosystem with the web of ecological niches bound together with trophic and other relations. The stationary dynamics of the ecosystem is characterized by the set of filled niches. The process of evolution is described in terms of niche composition change. Perspectives of the theory of self reproducing systems in biology are discussed. PMID- 1742473 TI - Some geometrical considerations on membrane insertion by exocytosis. AB - A two-dimensional random walk model is used to describe constitutive exocytic transport. Specifically, the possibility of attaining selective vesicle insertion by purely geometrical effects is studied. The distribution of vesicle insertion on the membrane and the average time of translocation are determined as a function of Golgi apparatus size and position, cell morphology and size, walk bias due to cytoplasmic streaming or differential movement on microtubules, and steric effects caused by other organelles. The simulations suggest that significant selectivity in targeting can result from adequate Golgi positioning, in accordance with the hypothesis of Golgi reorientation by the microtubular network (Singer and Kupfer, 1986, Annu. Rev. Cell Biol. 2, 337-365). The selectivity in targeting also depends on the cellular morphology. Segregation of vesicle insertion can be obtained in the transport to the cellular front end and lateral membrane surfaces of a quadrilateral cell, thus suggesting a geometrical component in the exocytic transport in polarized cells. PMID- 1742474 TI - Enzymes and theoretical biology: sketch of an informational perspective of the cell. AB - In the theoretical scenarios of biology, new insights can be gained by the introduction of information-processing and artificial intelligence concepts, helping to organize the explanation of the many intra- and inter-cellular phenomena that molecular biology is accumulating. Enzymes contain some of the immediate clues; the whole informational processing of prokaryotic cells is another central subject of search. Additionally, prolonging the informational perspective of the cell, a significant parallel can be drawn between informational processes in biological, social and artificial intelligence systems. A more tangible definition of biological complexity and biological intelligence emerges. PMID- 1742475 TI - Visualizing DNA replication sites in the cell nucleus. AB - Studies of DNA replication associated with the nuclear matrix have led to a radically new view of replication at the macroscopic level. It is proposed that individual replicons and their associated replicational assemblies (replisomes) are clustered together during active replication by attachment to the nuclear matrix at special sites termed 'clustersomes'. Direct visualization of replication sites in permeabilized cells by fluorescence microscopy following biotin-11-dUTP incorporation provides support for this model. Discrete replication granules are observed with sizes and numbers consistent with each granule being a site of replicon cluster synthesis. Distinct patterns of these sites are seen in different periods of S-phase. Both the individual granules and their early and late S-phase dependent patterns are strikingly maintained following extraction of the cells for in situ nuclear matrix structures. Similar results were obtained when probing in vivo sites of replication following incorporation of 5-bromodeoxyuridine. The three-dimensional organization of these replicational granules (clustersomes) is studied using confocal light microscopy and an appropriate multidimensional image analysis system. PMID- 1742476 TI - Bio Vision: microscopy in three dimensions. AB - Conventional electron microscopy is inadequate for visualizing the three dimensional networks supporting cell architecture: the cytoskeleton and nuclear matrix. Consequently, we have not appreciated the extent to which the cell, its biochemistry, and its molecular biology are structured. A new technology combining in situ cell fractionation and resinless section electron microscopy allows the visualization of cell structure in three dimensions and permits the localization of individual components. These techniques reveal a far richer cell architecture than had been assumed and will allow important problems of biology, which have not surrendered their secrets to a purely biochemical approach, to be addressed. PMID- 1742477 TI - T-prolymphocytic leukemia. PMID- 1742478 TI - Basic and clinical aspects of fibrinolysis and thrombolysis. PMID- 1742479 TI - A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia-positive chronic myelogenous leukemia. AB - The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML). The position of the breakpoint within the breakpoint cluster region (bcr) on Ph1 chromosome and the splicing pattern determine the species of the fused bcr-abl messenger RNA (mRNA). We tried to detect the two types of fused mRNAs in 57 chronic-phase cases of Ph1-positive CML using the polymerase chain reaction procedure (RT-PCR). The bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 17 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 34 patients, and both types of mRNA were detected in six patients. The platelet counts of patients who expressed b3-a2 mRNA or both types were significantly higher than those of patients who expressed only b2-a2 (841.5 v 373.5 x 10(9)/L; P less than .015), although there was no significant difference in the white blood cell counts or hemoglobin. This finding suggests a possibility that the type of bcr-abl mRNA may affect the thrombopoietic activity in CML. PMID- 1742480 TI - A randomized comparison of two doses of human lymphoblastoid interferon-alpha in hairy cell leukemia. Wellcome HCL Study Group. AB - One hundred thirty-eight patients with hairy cell leukemia were randomized to receive either a dose of 2.0 megaunits (MU)/m2 or a 10-fold lower dose of 0.2 MU/m2 of a highly purified natural alpha-interferon, administered daily for 28 days followed by a three times a week schedule. Ninety-seven of these patients had previously undergone splenectomy, but otherwise none of the patients had received prior therapy for their leukemia. The two doses were comparable in their effect on improving the neutrophil and platelet count, whereas the higher dose had a greater beneficial effect on the hemoglobin level and a greater antileukemic effect on the marrow. Acute toxicity in the form of a flu-like syndrome, neurologic side effects, neutropenia, and the need for platelet transfusions was observed less frequently in the low-dose group, as was the chronic fatigue syndrome. No neutralizing antibody activity was seen in the sera from 61 patients examined. Because of its beneficial effect on the neutrophil and platelet count and a lower degree of toxicity (ie, a superior therapeutic/toxicity ratio), the low dose is recommended as initial therapy in patients with hairy cell leukemia. This therapy may be followed by dose escalation once clinical improvement is observed. PMID- 1742481 TI - Long-term results of therapy with interferon-alpha for type II essential mixed cryoglobulinemia. AB - Severe type II essential mixed cryoglobulinemia (EMC) bears a poor prognosis. Treatment with corticosteroids and/or cytotoxic drugs infrequently results in long-term remissions, and is associated with significant toxicity. We conducted a prospective study with interferon (IFN) in 21 patients with severe type II EMC unresponsive to immunosuppressive regimens. They were treated with recombinant IFN-alpha 2a (18 patients) or with natural IFN-beta (three patients), alone, at a dosage of 3 megaunits (MU)/d for 3 months, followed by 3 MU every other day as maintenance. We observed 11 complete remissions, five partial remissions, and five minor responses. Of 16 patients observed for more than 1 year, 11 remained in remission for 14 to 40 months; five of them remained in complete remission for 18 to 40 months after withdrawal of treatment. Four patients discontinued treatment because of side effects. In four patients who relapsed while on maintenance therapy with recombinant IFN-alpha 2a, remission could be reinduced by treatment with natural IFN-alpha. The response rate of 77% achieved in this study prompts the use of IFN-alpha as a first-choice drug for type II EMC. PMID- 1742482 TI - Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. AB - To evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were intolerant to zidovudine because of neutropenia, we performed a randomized, open-label study in which patients were assigned to one of two groups. Zidovudine was discontinued in group A patients before instituting GM-CSF treatment and was restarted in a graduated fashion over 4 weeks. Group B patients continued on full-dose (1,200 mg/d) zidovudine therapy while beginning GM-CSF therapy. A total of 17 patients were entered, eight in group A and nine in group B. Five of eight patients in group A and seven of nine in group B had a history of Pneumocystis carinii pneumonia (PCP). All were homosexual males, except one female in group A who was the sex partner of a bisexual male with AIDS. All patients had neutropenia (absolute neutrophil count [ANC] less than 1,000/microL) while taking full-dose zidovudine. The mean CD4 (+/ SD) lymphocyte level was 37 (+/- 29)/microL and 39 (+/- 44)/microL in groups A and B, respectively. After randomization, patients were begun on subcutaneous GM CSF at a dose of 1.0 microgram/kg/d. Patients in group A received 2 weeks of daily GM-CSF, at which time zidovudine was restarted if the ANC was greater than 1,000/microL; if the ANC was less than 1,000/microL, the dose of GM-CSF was increased to 3.0 micrograms/kg, and at 2-week intervals either zidovudine was restarted or the dose of GM-CSF was increased to 5 micrograms/kg and then 10 micrograms/kg, to maintain the ANC greater than 1,000/microL. Group B patients received full-dose zidovudine concurrently with GM-CSF administration. The dose of GM-CSF was increased every 2 weeks if necessary to keep the ANC greater than 1,000/microL while maintaining full-dose zidovudine therapy. Patients in each group showed an increase in total white blood cell (WBC) count. Neutrophils and eosinophils were responsible for the majority of this increase. Patients in group A had a more rapid increase in WBC than those in group B; however, by week 8, the WBC in each group was essentially equal. Viral replication as measured by human immunodeficiency virus (HIV) p24 antigen (Ag) was decreased in four patients in each group, increased in one patient in each group, and remained unchanged in the remainder. The ability to culture virus from peripheral blood mononuclear cells was not changed by the regimen. The major toxicities of the regimen were fever and malaise.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742483 TI - In vitro myelopoiesis stimulated by rapid medium exchange and supplementation with hematopoietic growth factors. AB - We studied the effect of the combination of rapid culture medium exchange with the addition of the human hematopoietic growth factors interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (Epo) on the proliferation and differentiation of human long-term bone marrow cultures (LTBMCs). Individually and in combinations, IL-3, GM-CSF, and Epo were added to the culture medium of LTBMCs that were maintained with 50% medium volume exchange per day. The combination of IL-3 + GM-CSF + Epo generated the most prolific cultures with an order of magnitude increase in nonadherent cell production from weeks 2 through 8 in culture as compared with unsupplemented controls. Under these conditions, the cultures produced as many cells as were inoculated every 2 weeks and led to a greater than 2.5-fold expansion in terms of the number of nonadherent cells produced over a 6- to 8-week period. Furthermore, the LTBMCs produced nonadherent colony-forming unit-GM (CFU-GM) for more than 20 weeks. The rapid medium exchange combined with the addition of human hematopoietic CSFs significantly enhances the proliferation and differentiation of LTBMCs. These results indicate that addition of combinations of hematopoietic CSFs, together with a rapid medium exchange rate, can provide culture conditions that are suitable for the expansion of the progenitor cell pool and perhaps for the increased survival of hematopoietic stem cells in culture. Although these culture conditions still fall short of full reconstitution of functional human bone marrow, they provide an improved approach to hematopoietic cell culture that may permit the expansion and manipulation of progenitor cells in vitro. PMID- 1742484 TI - Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1. AB - The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10( 7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis. PMID- 1742485 TI - Differentiation-associated expression of prostaglandin H and thromboxane A synthases in monocytoid leukemia cell lines. AB - To elucidate the differentiation-associated expression of enzymes catalyzing arachidonic acid metabolism, we measured arachidonate metabolites by reverse phase high pressure liquid chromatography in monocytoid leukemia (ML-1, THP-1, and U937) and myeloid leukemia (KG-1) cell lines. Undifferentiated ML-1 or THP-1 cells produced trace amounts of eicosanoids via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Upon differentiation induced by phorbol ester (phorbol 12-myristate 13-acetate [PMA]), metabolites via the COX pathway were increased by 100-fold in ML-1 and THP-1 cells, while the LOX products remained barely detectable. All the COX metabolites were elevated, but thromboxane A2 (TXA2) formation was threefold higher in ML-1 cells than in THP-1 cells. Similar time-related increases in COX metabolites were observed in THP-1 cells induced to differentiate with retinoic acid. Undifferentiated U937 cells were capable of generating a much higher quantity of COX products than ML-1 or THP-1 cells, but, upon PMA-induced differentiation, COX products were increased by only two-fold to threefold over the undifferentiated cells and the total COX products in differentiated U937 cells were only one-seventh of those produced by differentiated ML-1 or THP-1 cells. KG-1 cells had an entirely different metabolic profile. They produced a large quantity of a metabolite coeluted with prostaglandin D2, and PMA had no effect on inducing changes in arachidonic acid (AA) metabolism. Increased COX metabolite formation in differentiated THP-1 and ML-1 cells was due to an enhanced level of prostaglandin H synthase enzyme mass, as measured by Western blot analysis. The TXA synthase activity was also increased by approximately 100-fold in PMA-induced ML-1 cells and 10-fold in THP 1 cells. These findings indicate that increased expression of prostaglandin H and TXA synthase enzymes is a feature of differentiated monocytoid leukemia cell lines. PMID- 1742486 TI - Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. AB - We describe the clinical and laboratory findings of 78 adult patients with T prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT-, CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2' deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8 phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin. PMID- 1742487 TI - All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. AB - Polymerase chain reaction (PCR) of bcl-2 provides an extremely sensitive method to detect minimal disease in approximately 50% of patients with non-Hodgkin's lymphomas (NHL). In an attempt to determine the clinical usefulness of this technique, we examined the bone marrow (BM) of 152 patients with advanced-stage NHL at the time of evaluation and after induction or salvage chemotherapy before autologous BM transplantation. The BM proved to be an accessible and reproducible tissue source to determine PCR positivity because all of the 102 patients examined had the same PCR-amplifiable breakpoint in their BM and lymph node. At the time of evaluation, PCR analysis in advanced-stage NHL patients added little additional information to morphologic analysis because each technique identified BM infiltration in approximately 70% of patients. PCR was significantly more useful in determining BM infiltration after induction or salvage therapy. At that time, approximately 50% of patients had morphologically normal BM, whereas PCR analysis remained positive in 100% of those with an amplifiable breakpoint. These observations were confirmed in a clinical trial attempting to induce remission in previously untreated low-grade advanced-stage NHL patients. In this series, PCR was positive in all patients after treatment although the BM was histologically uninvolved in 50% of cases, showing that conventional therapy did not eradicate bcl-2-positive cells. PMID- 1742488 TI - Prognostic correlation of plasma cell acid phosphatase and beta-glucuronidase in multiple myeloma: a Southwest Oncology Group study. AB - In 1982 a randomized trial of either alternating or syncopated VMCP/VBAP regimens for the treatment of active multiple myeloma was begun (Southwest Oncology Group Study 8229/30). A concurrent investigation was undertaken to evaluate the clinical importance and significance of cytochemically stainable plasma cell acid phosphatase (AP) and beta-glucuronidase enzymes (BG). Pretreatment bone marrow aspirates were available for analysis from 399 patients for AP and 398 patients for BG. The AP scores ranged between 42 and 395, and the BG scores ranged between 1 and 346. There was a significant increase of AP (P = .001) and BG (P = .002) in multiple myeloma as compared with a set of patients with benign plasmacytosis. The enzyme scores did not significantly relate to Ig idiotype of myeloma or other prognostic variables except that the BG scores varied significantly with the level of albumin (P = .03) and hemoglobin (P = .01). Analysis of patient groups with different levels of enzyme scores showed that 61 of 398 patients with an AP score of less than 130 had a poorer median survival of 1.7 versus 2.8 years for patients with higher scores (P = .001). In the multivariate analysis of survival, low AP score was an important prognostic factor (P = .006), but BG did not contribute significantly. It is suggested that the subset of patients presenting with low AP should be considered for specialized or more aggressive therapy. PMID- 1742489 TI - Iron absorption in hypotransferrinemic mice. AB - We used a unique animal model, the hypotransferrinemic (Htx) mouse, to examine the role of transferrin (Tf) in gastrointestinal iron uptake. Despite the absence of Tf, Htx animals hyperabsorb iron. Transfusion of red blood cells sufficient to normalize the hematocrit and reticulocyte count resulted in a return of iron absorption to normal values. These studies indicate that Tf does not play an obligate role in iron absorption, either as a carrier or as a humoral signal regulating absorption. Transfer of plasma or whole blood from Htx mice or from other animal models of iron hyperabsorption to normal mice did not cause an increase in iron absorption in recipient animals. Using the plasma or blood transfer approach, we have been unable to detect a humoral regulator of gastrointestinal iron absorption. PMID- 1742490 TI - Identification of four novel delta-globin gene mutations in Greek Cypriots using polymerase chain reaction and automated fluorescence-based DNA sequence analysis. AB - The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3' acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling. PMID- 1742491 TI - Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. AB - Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis. PMID- 1742492 TI - [Three cases of preprosthetic orthodontic extrusion]. PMID- 1742493 TI - [Clinical use of a computerized periodontal probe (Florida Probe System)]. PMID- 1742494 TI - [Chronicle of an emergency in the office and laboratory]. PMID- 1742495 TI - [Stress and the problem of pain in myofascial pain dysfunction syndrome (M.P.D.S.)]. PMID- 1742496 TI - Determination of the embryonic axes of Drosophila. AB - The principles of embryonic pattern formation have been studied extensively in many systems using classical experimental approaches. In Drosophila, a powerful combination of genetics and transplantation experiments, as well as molecular biology, have helped to elucidate the mechanisms that operate during oogenesis and early embryogenesis to establish a set of positional cues required for axis determination in the early embryo. In systematic searches for maternal effect mutations a small number of about 30 genes have been identified that specifically affect the process of determination of the embryonic axes. These 'coordinate' genes define four systems that determine the anteroposterior (AP) axis (three systems) and the dorsoventral (DV) axis (one system) independently. In the anteroposterior axis, the anterior system determines the segmented region of head and thorax, the posterior system determines the segmented abdominal region, and the terminal system is responsible for the formation of the nonsegmented termini at the anterior and posterior egg tips, the acron and telson. In contrast, pattern along the dorsoventral axis is determined by one system only. Although all four systems use different biochemical mechanisms, they share several properties. (1) The product of one gene in each system is localized in a specific region of the freshly laid egg and functions as a spatial signal. (2) In each system, this spatial information finally results in the asymmetrical distribution of one gene product that functions as a transcription factor. (3) This transcription factor is distributed in a concentration gradient that defines the spatial limits of expression of one or more zygotic target genes. The combined action of these three anteroposterior systems as well as the dorsoventral system defines the expression of zygotic target genes in at least seven distinct regions along the anteroposterior and at least three in the dorsoventral axis. These longitudinal and transverse domains provide a coarse spatial prepattern which is then further refined by the action and interaction of zygotic pattern genes. PMID- 1742497 TI - Specification of cell fate in the developing eye of Drosophila. AB - Determination of cell fate in the developing eye of Drosophila depends on cellular interactions. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, single cells are specified in regular intervals to become the R8 photoreceptor cells. Genes such as Notch and scabrous participate in this process suggesting that specification of ommatidial founder cells and the formation of bristles in the adult epidermis involve a similar mechanism known as lateral inhibition. The subsequent steps of ommatidial assembly involve a different mechanism: undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell is best understood. The key role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information--most likely encoded by boss on the neighboring R8 cell membrane--into the cell via its tyrosine kinase that activates a signal transduction cascade. Two components of this cascade--Sos and sina--have been identified genetically. sina encodes a nuclear protein whose expression is not limited to R7. Constitutive activation of the sevenless kinase by overexpression results in the diversion of other ommatidial cells into the R7 pathway, suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development. PMID- 1742498 TI - A genetic and molecular model for flower development in Arabidopsis thaliana. AB - Cells in developing organisms do not only differentiate, they differentiate in defined patterns. A striking example is the differentiation of flowers, which in most plant families consist of four types of organs: sepals, petals, stamens and carpels, each composed of characteristic cell types. In the families of flowering plants in which these organs occur, they are patterned with the sepals in the outermost whorl or whorls of the flower, with the petals next closest to the center, the stamens even closer to the center, and the carpels central. In each species of flowering plant the disposition and number (or range of numbers) of these organs is also specified, and the floral 'formula' is repeated in each of the flowers on each individual plant of the species. We do not know how cells in developing plants determine their position, and in response to this determination differentiate to the cell types appropriate for that position. While there have been a number of speculative proposals for the mechanism of organ specification in flowers (Goethe, 1790; Goebel, 1900; Heslop-Harrison, 1964; Green, 1988), recent genetic evidence is inconsistent with all of them, at least in the forms in which they were originally presented (Bowman et al. 1989; Meyerowitz et al. 1989). We describe here a preliminary model, based on experiments with Arabidopsis thaliana. The model is by and large consistent with existing evidence, and has predicted the results of a number of genetic and molecular experiments that have been recently performed. PMID- 1742499 TI - Cell polarity and microtubule organisation during mouse early embryogenesis. AB - We have studied the distribution and the role of microtubules in the major developmental events occurring during early development of the mouse. These events are the setting up of asymmetries within blastomeres, the process of asymmetrical cell division and the changes in cellular organisation taking place during epithelial differentiation. PMID- 1742500 TI - Dominant gain-of-function mutations that lead to misregulation of the C. elegans heterochronic gene lin-14, and the evolutionary implications of dominant mutations in pattern-formation genes. AB - The heterochronic gene lin-14 controls the temporal sequence of developmental events in the C. elegans postembryonic cell lineage. It encodes a nuclear protein that is normally present in most somatic cells of late embryos and L1 larvae but not in later larval stages or adults. Two lin-14 gain-of-function mutations cause an inappropriately high level of the lin-14 nuclear protein late in development. These mutations delete 3' untranslated sequences from the lin-14 mRNAs and identify a negative regulatory element that controls the formation of the lin-14 protein temporal gradient. The 21 kb lin-14 gene contains 13 exons that are differentially spliced to generate two lin-14 protein products with variable N terminal regions and a constant C-terminal region. No protein sequence similarity to any proteins in various databases was found. The temporal and cellular expression patterns of lin-14 protein accumulation is altered by mutations in the heterochronic genes lin-4 and lin-28. The lin-4 gene is required to down-regulate lin-14 protein levels during the mid-L1 stage. The lin-4 gene product could be the trans-acting factor that binds to the negative regulatory element in the lin 14 3' untranslated region. In contrast, the lin-28 gene activity positively regulates lin-14 protein levels during early L1. Thus, these genes act antagonistically to regulate the lin-14 temporal switch. The normal down regulation of lin-14 within 10 h of hatching is not determined by the passage of time per se, but rather is triggered when feeding induces post-embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742501 TI - Genetic and cytological control of the asymmetric divisions that pattern the Volvox embryo. AB - The highly regular pattern in which approximately 2000 small somatic cells and 16 large reproductive cells (or 'gonidia') are arranged in a typical asexual adult of Volvox carteri can be traced back to a stereotyped program of embryonic cleavage divisions. After five symmetrical divisions have produced 32 cells of equal size, the anterior 16 cells cleave asymmetrically, to produce one small somatic cell initial and one larger gonidial initial each. The gonidial initials then cease dividing before the somatic cell initials do. The significance of the visibly asymmetric divisions is underscored by genetic and experimental evidence that differences in size--rather than differences in cytoplasmic quality--are causally important in activating the programs that cause small cells to become mortal somatic cells and large cells to differentiate as reproductive cells. A number of loci, including at least five mul ('multiple gonidia') loci, appear to be responsible for determining where and when asymmetric divisions will occur, since mutations at these loci result in modified temporal and/or spatial patterns of asymmetric division in one or more portions of the life cycle. But the capacity to divide asymmetrically at all appears to require a function encoded by the gls (gonidialess) locus, since gls mutants fail to execute any asymmetric divisions. Second-site suppressors of gls that have been identified may encode other functions required for asymmetric division. Cytological and immunocytochemical studies of dividing embryos are being undertaken in an attempt to elucidate the mechanisms by which cell-division planes are established--and shifted--under the influence of such pattern-specifying genes. Studies to date clearly indicate a central role for the basal body apparatus, and particularly its microtubular rootlets, in establishing the orientation of both the mitotic spindle and the cleavage furrow; but it remains to be determined how behavior of the division apparatus becomes modified during asymmetric division. PMID- 1742502 TI - Gene activation in the amphibian mesoderm. AB - Cell potency is progressively restricted in amphibian development by a series of cellular interactions called inductions. The mesoderm is believed to develop in response to the earliest known induction, in which vegetal cells of the blastula divert overlying animal hemisphere cells away from epidermal and towards mesodermal fates. We describe two early markers of mesodermal differentiation in Xenopus laevis, both mRNAs that encode DNA-binding proteins of the helix-loop helix family. One is a frog homologue of MyoD, a gene that in transfection experiments can convert cultured fibroblasts into myoblasts. Xenopus MyoD (XMyoD) is expressed in the early myotomes, from which the axial musculature develops. The accumulation of XMyoD RNA precedes that of transcripts from the cardiac actin gene, until now the earliest known marker of the muscle lineage, this result indicating that XMyoD could play a role in initiating muscle differentiation in normal development. We show by microinjection of synthetic RNA that XMyoD can indeed activate muscle-specific gene expression in animal cap cells, which would normally form only ectoderm. However, the XMyoD-injected animal caps did not produce differentiated muscle, suggesting that additional specific factors are required for full myogenesis. The other mRNA is a relative of the twist gene of Drosophila, which is required for mesodermal differentiation in flies. This gene (Xtwi) is expressed widely in the early frog mesoderm, but not, however, in the myotomes, where XMyoD is expressed. Later, the Xtwi gene is activated, in response to a second induction, in the developing neural crest. PMID- 1742503 TI - Clinical presentation and natural history of chronic persistent hepatitis. A multicentre retrospective study on 1197 cases. AB - To obtain data on the clinical presentation and the course of the disease of biopsy-proven chronic persistent hepatitis (CPH), we coordinated a multicentre retrospective study on 1197 patients observed in 16 liver units throughout Italy from 1975 to 1985. Most patients were asymptomatic and CPH was often diagnosed either after a chance finding of liver enlargement, or increased serum aminotransferases and/or HBsAg antigenemia. Of the 1197 patients, 534 (44.6%) were HBsAg-positive and 663 (55.4%) were HBsAg-negative. HBeAg was tested in 356 of the 534 positive cases and detected in 58.4% of them. This percentage was higher (80%) in patients under 20. Hepatitis delta virus infection (HD-Ag in liver tissue and/or anti-HD in serum) was detected in 28 (14.7%) of the 191 patients tested on presentation. Liver function tests showed mild hepatic involvement in both HBsAg-positive and negative cases, a pronounced derangement being observed only in patients with HDV infection. A second liver biopsy was performed in 212 patients (144 HBsAg positive and 68 HBsAg negative) and the outcome of the disease was evaluated only in these 212 patients. Of the 144 HBsAg positive cases followed-up from one to ten years (median 4 years), 47 recovered, 70 remained unchanged and 27 developed chronic active hepatitis or cirrhosis. Clearance of HBsAg was uncommon even in patients who recovered. Being under 15 years of age favourably affected the course of the disease, while HDV infection was correlated to an unfavourable outcome. Among those patients who were HBeAg positive on presentation and who underwent a second affect the outcome. Of the 68 HBsAg-negative clearly affect the outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742504 TI - Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis. AB - The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID induced gastric and duodenal mucosal lesions and symptoms. PMID- 1742505 TI - Plasma osteocalcin levels in liver cirrhosis. AB - Osteocalcin, a recently identified protein, is produced by osteoblasts in the bone tissue. Its plasma level is a good marker of bone metabolism and is reduced in the presence of 'osteodystrophia', commonly found in cholostatic liver diseases. We assayed plasma osteocalcin levels in 20 cirrhotic patients and compared the values with those of 22 healthy controls. In the same patients we also measured the liver function, clotting and mineral metabolism indexes and calcitonin plasma levels. Osteocalcin levels were significantly lower in liver disease patients than in controls (5.53 ng/ml S.D. 2.57 vs 7.79 ng/ml S.D. 2.23; p less than 0.01) and calcitonin plasma levels were much higher in cirrhotics (130.18 pg/ml S.D. 212.30 vs 28.9 pg/ml S.D. 13.09; p less than 0.05). We think that the low osteocalcin levels observed in cirrhotics may be a consequence of "hepatic osteodystrophy" due to low vitamin D and calcium plasma levels. PMID- 1742506 TI - Eating behaviour: investigation on the recursive components of hunger sensation by iterative rhythmometry. AB - The periodic components of hunger have been investigated in the spectrum of ultradian and circadian rhythms by means of iterative rhythmometry analysis, a method for resolving harmonic components in time series data. The cyclical scanning has been applied in human subjects with eating disorders associated with leanness, ponderosity and obesity. The sensation of hunger was rhythmometrically resolved into ultradian and circadian components which are peculiar for the group investigated. Harmonic modelling can be used on an individualized basis for group specific configurations and, on that basis, for unphysiologic patterns. A comparison with the rhythmometric model of healthy subjects may have a practical use in identifying and manipulating behavioural disorders in the propensity to eat. PMID- 1742507 TI - Gastric antral erosions and Helicobacter pylori infection in cirrhotic patients: a pilot controlled study of oral bismuth vs ranitidine therapy. AB - A controlled study was performed comparing bismuth and ranitidine oral therapy in the treatment of chronic antral erosions and chronic active gastritis and in clearing Helicobacter pylori in cirrhotic patients. Forty four patients took part in the randomized study. H pylori was present in more than 50% of the patients in the study. There was a close association between the presence of H pylori and inflammatory activity of gastritis at an antral level (p less than 0.001). CBS was significantly better than ranitidine in clearing H pylori (p less than 0.001) and reducing inflammatory activity of gastritis (p less than 0.001). This reduction was related to H pylori clearance. No action of the two medications was observed in improving endoscopic findings of erosive gastritis. H pylori clearance did not influence amelioration of endoscopic chronic erosive antral gastritis (EG) in cirrhotic patients. These findings suggest that H pylori does not seem to play a pathogenetic role in the aetiology of EG in cirrhotic patients while it represents an important factor in determining and maintaining the inflammatory activity of histologically confirmed gastritis in these patients. PMID- 1742508 TI - Common bile duct and sex, age and body mass index in normal humans: an ultrasonographic study. AB - A probable relationship between Common Bile Duct (CBD) size and sex, age and Body Mass Index (BMI) was investigated in healthy volunteers. Real-time ultrasonography was employed to visualize gallbladder and CBD. No change of CBD size related to sex and BMI was found. A significant increase of CBD related to age was recorded. PMID- 1742509 TI - Effect of lactobacillus acidophilus and bifidobacterium bifidum on rectal cell kinetics and fecal pH. PMID- 1742510 TI - Infusional therapy for post-surgical biliary stones. AB - A variety of effective non-surgical forms are used for dealing with retained and recurrent biliary stones. These are endoscopic papillotomy, infusional therapy, intraductal laser or electrohydraulic lithotripsy and extracorporeal shock waves. Saline washout or chemical stone dissolution is currently used in high-risk subjects or in cases in which endoscopic papillotomy fails. For many years now drugs that should dissolve stones topically have been tested by direct infusion into the biliary tract. This approach has given better results over the last ten years with the adoption of Monooctanoin (Mo) and more recently Methyl tertbutyl ether (MTBE). Both preparations have their pros and cons, which are weighed. PMID- 1742511 TI - Problems of gastrointestinal endoscopy in Italy. PMID- 1742512 TI - Patient's assessment of an information booklet on Crohn's disease written by a patient. AB - Patients with Crohn's disease want information about the condition. "So you've got Crohn's disease", an information booklet written by a patient was sent to patients for evaluation. Most found it useful, particularly in the practical advice, and suitable for all patients with Crohn's disease. Patients can be a valuable source of information for other patients and doctors. They should be encouraged to share their experiences. PMID- 1742513 TI - Hepatitis C virus antibodies in chronic liver diseases of different aetiology. AB - To define the prevalence of Hepatitis C Virus (HCV) infection in patients with chronic hepatitis or cirrhosis of any aetiology, we tested a group of 372 consecutive subjects with biopsy-proven chronic liver disease (CLD) for anti-HCV antibodies, excluding active drug-addicts and alcoholics. Our results show that in Southern Italy HCV infection is widespread among subjects with cryptogenic chronic liver disease, as well as in liver diseases with features of autoimmunity (71.7% and 66.7% anti-HCV positive, respectively). Anti-HCV is infrequent among non drug-addicted HBsAg positive subjects (4.7%), and bears no relation to hepatitis D superinfection. Subjects with CLD and a history of parenteral exposure are almost always anti-HCV positive (89.2%). Patients with HBV-related CLD and previous drug-addicts are on the average younger than other disease groups, irrespective of their HCV status. Among subjects whose CLD is related to parenteral exposure, cryptogenic or autoimmune no increase in the rate of anti HCV positivity seems to bear a parallel relationship to age. No known risk factor for parenteral transmission, other than use of blood or blood products and previous drug-addiction, can be clearly related to HCV infection. No trend to familiar clustering of HCV-induced liver disease is apparent. Liver disease severity, as assessed by transaminase levels and liver histology, does not correlate to anti-HCV status. PMID- 1742514 TI - Protective effect of cyanidin (IdB 1027) against aspirin-induced fall in gastric transmucosal potential difference in normal subjects. AB - The effect of the natural flavonoid cyanidin (IdB 1027), 1200mg daily for 8 days, on the fall in gastric transmucosal potential difference induced by a single dose of aspirin (1000mg by nasogastric tube) was evaluated in 7 normal male volunteers. As compared to pretreatment values, IdB 1027 caused a significant reduction in both the percentage fall in transmucosal potential difference at the time of peak aspirin effect (from 37 +/- 18% to 18 +/- 5%, p less than 0.05) and the area under potential difference baseline (from 811 +/- 624 mvolt. min to 338 +/- 150 mvolt. min, p less than 0.05). These results provide evidence for a protecting effect of IdB 1027 against aspirin-induced gastric mucosal damage in man. PMID- 1742515 TI - A comparison of nizatidine and ranitidine in the maintenance treatment of duodenal ulcer. A randomized, double blind, multicentre, 2-year study. AB - One hundred and eight patients with an endoscopically documented healed duodenal ulcer (DU) participated to a multicentre, randomized, double-blind, long-term study. The study was planned with the aim to compare the efficacy of nizatidine 150 mg with ranitidine 150 mg in preventing relapse during the 2 years following the DU healing. Fifty four patients were assigned to each treatment. Endoscopic examinations were scheduled at 6, 12 and 24 months. Clinical evaluations were performed every two months. Routine laboratory tests were investigated at the beginning of the study and at each of the scheduled endoscopies. STATISTICS: chi squared test with Yate's correction, Student's t test for unpaired data, Wilcoxon Rank Sum test and Logrank test. Twenty five patients dropped-out: 15 in the nizatidine and 10 in the ranitidine group. The cumulative relapse rate was 18% for nizatidine and 21% for ranitidine treatment (p:ns). Both drugs resulted safe, as only minor side effects were registered. IN CONCLUSION: nizatidine is as effective and safe as ranitidine in the long-term (2 year) treatment of DU. PMID- 1742516 TI - Unusual side effects of mesalazine. PMID- 1742517 TI - Exocrine pancreatic involvement in Wegener's granulomatosis. A case report. AB - A rare case of exocrine pancreatic damage in a patient with Wegener's granulomatosis is reported. The pancreatic amino acid consumption test, a new tubeless technique, revealed exocrine pancreatic insufficiency before and after immunosuppressive therapy. The presence of exocrine pancreatic insufficiency in this patient raises the possibility of pancreatic involvement in Wegener's granulomatosis. PMID- 1742518 TI - Epithelioid hemangioendothelioma of the liver: report of two cases. AB - Epithelioid hemangioendothelioma is a very rare tumour of vascular origin, the most peculiar feature of which is that it is composed of endothelial cells closely resembling epithelial cells. Confirmation of its endothelial origin is achieved by positive staining for Factor VIII-related antigen or by the demonstration of Weibel-Palade bodies by electron microscopy. We report two cases of primary epithelioid hemangioendothelioma of the liver that occurred in our center in the last ten years. The first patient is a 21 year old woman who presented with a right upper quadrant pain and an echographic finding of multiple hepatic lesions suggestive of metastases. The second patient is a 32 year old woman operated on for a cerebral glioma, in whom an abdominal CT scan, performed in view of radiotherapy, revealed multiple hepatic lesions, originally interpreted as being metastatic. In both cases, diagnosis was made based on the histologic examination of biopsies have been adopted in each case: the first patient has undergone successful liver transplantation. In the second patient an attentive surveillance appeared to be the best option, due to the presence of a previous cerebral glioma. PMID- 1742519 TI - Physiopharmacology of the peristaltic reflex: an update. AB - The peristaltic reflex is one of the simplest models which can be used to study the function of enteric neurons by recording intestinal motor activity. Peristalsis consists of a coordinated, aborally propagating motor activity which requires the functional integrity of receptor pathways, excitatory and inhibitory neural pathways and neuromuscular junctions. Luminal distension elicits polarized responses: an ascending excitatory response (ascending contraction) and a descending inhibitory response (descending relaxation). The present paper reviews the most recent acquisitions on the neural pathways and neurotransmitters involved in the regulation of the peristaltic reflex. PMID- 1742520 TI - An overdose of scientific information? PMID- 1742521 TI - L-alanine plasma levels after oral loads in non-alcoholic liver cirrhosis: relationship with urea extraformation and ammoniogenesis. AB - In the post-absorptive stage L-alanine is the main source of alpha-amino-nitrogen reaching the liver as glucose precursor. This aminoacid has been used as a measure of urea synthesis capacity in several pathologic conditions, but it has not been employed sistematically in patients with liver cirrhosis. We tried to address this issue by evaluating: a) L-alanine plasma levels, b) urea extraformation (UE), and c) ammoniogenesis after oral L-alanine (0.25 and 0.50 g/kg b wt) in healthy control subjects and in patients with nonalcoholic compensated (Child-Pugh's A class) and decompensated (Child-Pugh's B and C) liver cirrhosis. L-alanine plasma levels after oral load were higher and lasted longer in cirrhotics as compared to controls. Furthermore, after L-alanine oral load, significantly higher ammonia plasma levels were observed in cirrhotics than in controls. Changes in the urea extraformation were comparable in cirrhotics and controls. Both delayed L-alanine elimination from plasma and L-alanine-induced hyperammoniemia were more evident in decompensated cirrhotics and related to L alanine dose. PMID- 1742522 TI - Hepatitis A in Italy: epidemiology and suggestions for control. AB - Seroepidemiologic and surveillance data show that hepatitis A is declining in both Northern and Southern Italy, in the latter the decline has been more recent. Every year about two thousand cases of acute disease occur. Shellfish consumption and travel to endemic areas are at present the most important risk factors in Italy. Use of immunoglobulin is effective in controlling outbreaks and preventing hepatitis A among travellers. Active immunization for travellers to endemic areas will be recommended, when a vaccine will be available. Adequate cooking of shellfish is at present the only advisable measure to prevent the risk represented by their consumption. Acute morbidity and the occurrence of outbreaks suggest the need to keep our attention on hepatitis A infection in Italy. PMID- 1742523 TI - Changing epidemiology of hepatitis A virus (HAV) infection: a comparative seroepidemiological study (1979 vs 1989) in north-east Italy. AB - A comparative seroepidemiological study (1979 vs 1989) on HAV infection, was carried out in children and adolescents from North-East Italy. Anti-HAV was tested in 850 subjects 6 to 8 years of age and the results were compared to those observed in 1979, in 462 subjects of the same age range and from the same geographical area. Overall anti-HAV prevalence was 1.9% (ranging from 0.5 to 5.2) in 1989 vs 32.5% (ranging from 7.8 to 70.7) in 1979. This dramatic decline of HAV infection in children and adolescents reflects the improved sanitation standard of our country but, on the other hand, indicates that the number of non-immune adults is increasing, with a higher risk of symptomatic infection in the near future. PMID- 1742524 TI - Changing pattern of hepatitis B infection in children: a comparative seroepidemiological study (1979 vs 1989) in north-east Italy. AB - Hepatitis B infection was endemic in Italy and household transmission has been considered to be the main mode of HBV spread. Prevalence of HBsAg positive subjects was therefore higher in children than in adults. Serum samples from 500 children (aged 6-15 year) without overt liver disease were tested for HBV serum markers in 1979. Serological evidence of HBV infection was present in 16% of the subjects. To verify a possible decline of HBV infection we designed a seroepidemiological study in school children from the same town. Three classes of age (6 yrs, 10 yrs, 14 yrs) were selected. Children were recruited from those attending primary and secondary schools using a systematic cluster sampling. After parents' informed consent sera were collected in May 1989. All were tested for anti-HBc: anti-HBc + ve sera were then tested for HBsAg and anti-HBs (EIA Abbott Lab., Chicago, Ill. USA). Of the 1635 children one was HBsAg positive and 21 were positive for any HBV marker. Both the prevalence of HBsAg and that of any HBV marker were significantly lower (p less than 0.001) in 1989 when compared to the corresponding age-class of 1979. PMID- 1742525 TI - Increased risk for gallstone disease in subjects operated on for partial gastrectomy with gastro-jejunostomy (BII operation). AB - The prevalence of cholelithiasis has been investigated in 301 male subjects (age range 35-60 years) operated on for partial gastrectomy with gastro-jejunostomy (BII), in 277 unoperated peptic ulcer patients (age range 30-60 years) and in a control population of 281 factory's workers (age range 31-58 years). The prevalence of gallstone disease resulted significantly higher in BII operated subjects (23.9%) than in unoperated (9%) and controls (8.5%). No difference was found between unoperated peptic ulcer patients and controls. These results indicate that BII operation is a high risk condition for cholelithiasis while peptic ulcer disease does not constitute a favourable factor for gallstone formation. PMID- 1742526 TI - Does the combination of a human fibrin sealant with ranitidine accelerate the healing of duodenal ulcer? AB - Human fibrin sealant (Tissucol) has been used in surgery for its haemostatic and sealing actions and stimulating effect on tissue regeneration. Recently it has been used in endoscopy, but controlled trials are not yet available. The aim of this study was to evaluate the efficacy of Tissucol on the healing rate of duodenal ulcers (DU). Thirty nine previously untreated DU patients received ranitidine 150 bid plus endoscopically applied either placebo (19 patients) or Tissucol (20 patients). Sixty-five percent of the patients in the Tissucol group and 21% in the control group healed after two weeks (p less than 0.02), 75 and 52.6% respectively after 4 weeks (NS). The endoscopic application of Tissucol seems to influence the healing of duodenal ulcer and its use could be suggested in selected patients with DU. PMID- 1742527 TI - Effect of omeprazole on H. pylori after two weeks of treatment. AB - The "clearing" effect of omeprazole 20 mg/daily on Helicobacter pylori (HP) was studied in 32 HP positive patients with duodenal ulcer (DU). Endoscopy and antral biopsies were made before and after two weeks of treatment with Omeprazole. HLO test and histology after Giemsa stain were used for the detection of HP. Fourteen of 28 (50%) initially HLO positive and 12 of 30 (40%) initially histological HP positive patients became HP negative. Nine of 23 (39%) patients, initially HP positive by both methods became HP negative. "Clearing" of HP in this particular group of patients did not have any influence on ulcer healing. It is concluded that omeprazole used for two weeks has a clearing effect on HP in a high enough percentage of patients with DU. PMID- 1742528 TI - Propranolol for metronidazole-resistant giardiasis. PMID- 1742529 TI - Double pylorus: report of two cases and review of the literature. AB - Double pylorus is a rare condition consisting of a double communication between gastric antrum and duodenal bulb; in most cases it is a complication of penetrating ulcer, sometimes it is a congenital abnormality. The prevalence of this rare anomaly ranges from 0.02% to 0.13%; the male:female ratio is about 2:1. Two cases of acquired double pylorus are reported with a review of the literature. The first case represented an occasional report; in the other one the development of double pylorus from confluent prepiloric and bulbar ulcers was documented through serial endoscopies. Both patients were affected with chronic renal failure and referred previous treatment with diclofenac; however, their relationship with double pylorus onset remains unproven. PMID- 1742530 TI - Prolonged viral hepatitis type A with cholestasis: case report. AB - We describe a clinical case of an eleven year old boy with a protracted cholestatic form of viral hepatitis type A. The role of a macrolide antibiotic in the determinism of this form of hepatitis is discussed. PMID- 1742531 TI - Wandering spleen presenting as an evanescent abdominal mass. PMID- 1742532 TI - Experimental gastric cancer. AB - Since Sugimura and Fujimura (1967) succeeded in selectively inducing gastric carcinomas in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (1), similar models for the induction of gastric carcinomas in other species by using MNNG and its ethyl derivative N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) have been established. The susceptibility to gastric carcinogenesis, the histologic types of gastric carcinomas induced, and their biological behavior depend on the mode of treatment, species, strain and/or sex. The organ specificity of MNNG correlates well with the level of DNA methylation in target and non-target tissues following oral administration in rats. The high concentration of methylated DNA bases in the stomach mucosa appears to result from thiol-mediated acceleration of the decomposition of MNNG. Experimental gastric carcinogenesis is markedly modified by various factors and agents, including bile reflux, bile acids, sodium chloride, and ulceration, indicating that both host and environmental factors contribute significantly to gastric carcinogenesis by chemical carcinogens. PMID- 1742533 TI - Zinc and other trace elements in liver cirrhosis. AB - Alterations in trace element concentrations may be observed in patients with chronic liver disease. Notably, selenium and zinc levels are reduced both in serum and in liver tissue of cirrhotic patients. Low selenium levels have been involved in the pathogenesis of liver damage as this element is important in controlling the levels of toxic oxygen radicals in the cells. Zinc deficiency has been involved in the pathogenesis of a number of clinical findings in chronic liver disease. These include the possible role of zinc deficiency in the pathogenesis of hepatic encephalopathy, by inducing alterations in urea metabolism. In CC14 cirrhotic rats oral zinc supplementation reduces ammonia levels and increases OCT activity in the liver. Oral zinc supplementation has been also proposed in the treatment of cirrhotic patients with chronic hepatic encephalopathy, the results however are not yet conclusive. PMID- 1742534 TI - Again with problems of gastrointestinal endoscopy. PMID- 1742535 TI - Efficacy and safety of clebopride in functional dyspepsia. PMID- 1742536 TI - Lymphocyte traffic and adhesion molecules in the gut. PMID- 1742537 TI - Treatment of chronic hepatitis C with recombinant interferon alfa. AB - We studied the clinical course and the effect of alfa interferon treatment in sixty-six patients of Southern Italy suffering from chronic hepatitis C virus. The patients were randomly assigned to the control group (33 patients without treatment) or to the group treated with 3MU of interferon three times a week for six months. Alanine transaminase (ALT) levels normalized in 17 of the 33 treated subjects (52%) within two months of treatment. Seven of these "responders" relapsed at the end of the six-month treatment period, but ALT normalized in these patients after resumption of interferon at the same dosage. None of the non responders on 3MU for four months showed improvement even when the dose was increased to 6MU. Our results coincide with other reports on interferon treatment in hepatitis C virus. Further studies are required to clarify whether or not higher doses at the onset of treatment increase the number of responders and decrease the frequency of relapses. PMID- 1742538 TI - Rifaximine versus neomycin in the treatment of portosystemic encephalopathy. AB - In 14 patients with cirrhosis and chronic portosystemic encephalopathy, the effectiveness of treatment with a new non-assorbable antibiotic (rifaximine) was compared to neomycin. The parameters evaluated were: bradylalia, flapping tremor, performance, visual evoked potentials and the trial making test. Both treatments were combined with lactulose. The analysis of results showed a rate of positive results in the patients treated with rifaximine greater than that with neomycin. Differences, however, were not significant. PMID- 1742539 TI - The spontaneous bacterial peritonitis in cirrhotic patients. To a new gold standard. AB - Of 282 consecutive ascites prospectively collected in 54 months, Spontaneous Bacterial Peritonitis (SBP) was diagnosed in 8.5% of the cases, "probable" SBP in 31.1%, Bacteriascites (BA) in 3.5% and Sterile Ascites (SA) (negative ascitic fluid culture with PMN less than 250/mm3) in 74.8%. Escherichia Coli (41.6%) and Staphylococcus Epidermidis (60%) were the most frequent pathogens isolated in patients with SBP and BA, respectively. With regards to in-hospital mortality, 18% of patients with BA and 50% with SBP died; the mortality seemed to be related to the degree of hepatic and renal damage, to a higher peripheral and ascitic WBC concentration and to a lower pH of ascitic fluid (FA). When the comparative analysis was applied to the four groups of ascites, a different distribution of clinical signs and biohumoral parameters appeared. As a matter of fact, abdominal pain, fever and rebound tenderness resulted significantly more frequent in SBP and "probable" SBP. Furthermore, the mean values of peripheral and ascitic WBC concentration, of serum creatinine and of ALT were statistically higher in SBP and "probable" SBP than in SA and BA groups. The strict relationship, both symptomatologic and biochemical, between SA and BA on the one hand and between "probable" SBP and SBP on the other, prompted us to conclude that "probable" SBP and SBP represent different patterns of the same disease. Therefore, the subclassification in the four groups outlined above would not be in accordance with the clinical practice and could give rise to the physician's confusion and uncertainty. PMID- 1742540 TI - Action of glucomannans on complaints in patients affected with chronic constipation: a multicentric clinical evaluation. AB - Chronic constipation is a very frequent disease in western countries but fibres can often solve the problem. In the present study, authors tested the efficacy and the acceptability of glucomannans, hydrophylic carbohydrates with a high degree of viscosity, in 93 patients affected with chronic constipation. The multicentric, open and non-controlled study was divided into an initial phase (treatment with 1g of glucomannans t.i.d. for 1 month) and a maintenance phase (1g b.i.d. for one month). We evaluated both objective parameters (number of days per week with bowel movements and number of enemas) and abdominal symptoms. After one month all assessed parameters showed a statistically significant improvement lasting through the second month. Glucomannans were well accepted and devoid of relevant side-effects. In conclusion, considering their efficacy and tolerability, they can be proposed as an ideal therapeutic tool in the management of chronic constipation symptoms. PMID- 1742541 TI - Spontaneous rupture of the gallbladder and haemoperitoneum in a patient with cardiac valve prostheses. AB - A case is reported of isolated spontaneous rupture of the gallbladder with obstructed cystic duct and a stone in the cystic cavity, in a patient on anticoagulant treatment after cardiac valve replacement. The mechanism of the onset, the diagnosis and the treatment of the lesion are discussed together with a review of the literature. PMID- 1742542 TI - Gastric cancer in Italy. AB - Although Gastric Cancer (GC) death rates are decreasing worldwide, in high risk areas GC is still a major public health problem. Italy is one of the European countries with the highest mortality rates for GC (males: 17.3; females: 8.2 x 100,000 inhabitants in 1987) which represents the third cause of death due to cancer in 1987, accounting for over 14,000 deaths per year (10% of cancer deaths). Reasons for the geographic variability in GC occurrence within the country are reviewed, discussing the results of two recent analytical epidemiological studies carried out in Italy. These large case-control studies focused on dietary factors, involving high and low-risk areas for GC (Florence, Siena, Forli, Imola, Cremona, Genoa, Cagliari, and Milan). Low socio-economic status, family history of GC, residence in rural areas were associated to GC risk, while migration from southern areas and body mass index were inversely related to GC. Consumption of traditional soups, meat, salted and dried fish, cold cuts and seasoned cheeses, as well as the intake of animal proteins and nitrites were related to an increased GC risk. On the contrary consumption of fresh fruit, citrus fruit, raw vegetables, spices, garlic and olive oil, and vitamin C, E and beta-carotene intake were found to be protective factors. Among diet-related factors, preference for salty foods and frequent broiling were positively related to GC, while the longstanding availbility of a refrigerator or freezer and the habits of consuming frozen foods were associated with decreased GC risk. These results are discussed in detail, considering the main hypotheses on GC carcinogenesis. PMID- 1742543 TI - Diagnostic approach to primary sclerosing cholangitis: open questions. AB - Over the last ten years the incidence of primary sclerosing cholangitis (PSC) presented a progressive increase, showing an association with chronic inflammatory bowel disease (IBD) in 50-70% of the cases. Nowadays, however, the prevalence of PSC is still unknown, mainly because of its difficult identification. In contrast to primary biliary cirrhosis (PBC), which is strongly associated with the presence of anti-mitochondrial antibodies (AMA) in serum, a similar reliable diagnostic marker has not yet been demonstrated in PSC. In this review we tried to investigate the controversial diagnostic aspects which may interfere with the initial assessment of PSC syndrome. Alkaline phosphatase (ALP) and endoscopic retrograde cholangiography (ERC) are actually the two cornerstones of the clinical setting, but if alone, they do not seem to provide sufficient accuracy. Furthermore, liver biopsy, perhaps more sensitive but not always specific, is generally performed too late. In our opinion, epidemiologic studies are needed in Italy and elsewhere in order to evaluate PSC prevalence. Moreover, the analysis of these results might lead to an earlier detection of the disease and, perhaps, favourably modify its natural history. PMID- 1742544 TI - The descriptive epidemiology of primary liver cancer in Italy. AB - Using figures from the official death registry, we studied the descriptive epidemiology of primary liver cancer (PLC) in Italy from 1969 to 1985. The annual age-standardized mortality rate rose from 3.7/100,000 in 1969 to 4.7/100,000 in 1985, reaching the peak of 6.5/100,000 in 1983. The male/female ratio increased from 1.2:1 in 1969 to 2:1 in 1985. The age-specific mortality rate was very low in subjects under 55 years of age and peaked in subjects in their seventies and eighties. The rate was higher for men in all age-groups. The highest proportion of deaths (32%) was observed in the 65-74 year age group. The median age of death for patients with PLC was 10 years older than the median age for patients who died of alcoholic liver cirrhosis, but similar to that of patients who died of liver cirrhosis due to other causes. The highest regional age-standardized mortality rate was reported in Lombardia, Lazio and Veneto respectively, where hepatitis B virus (HBV) infection is less endemic than in the southern regions and the Islands. It should be kept in mind that these findings are not extremely accurate because they are based on mortality figures, where the contamination with metastatic cases is practically unavoidable; furthermore, their validity and comparability are not first-rate due to the wide variation in diagnostic accuracy and registration completeness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742545 TI - Close connections between endoscopy and gastroenterology. PMID- 1742546 TI - Education and training in gastrointestinal endoscopy. PMID- 1742547 TI - Microdetermination of hyaluronic acid in human urine by high performance liquid chromatography. AB - A high performance liquid chromatographic (HPLC) system is described for determination of the unsaturated disaccharide (delta Di-HA) derived from hyaluronic acid (HA) in human urine by digestion with hyaluronidase SD. The effects of eluents on the separation of delta Di-HA and delta Di-0S, which is derived from the reaction of chondroitin with the enzyme, have been studied. The established chromatographic conditions were as follows--column: a stainless steel tube (4 mm i.d. x 250 mm) packed with TSKgel NH2-60; eluent: a mixture of acetonitrile and 0.1 M Tris-HCl buffer containing 0.1 M boric acid and 10 mM sodium sulphate, pH 7.0 (64:36, v/v). The strong fluorescence of unsaturated disaccharide after the reaction with 2-cyanoacetamide in alkaline medium was used for post-column detection. The calibration curve for delta Di-HA was linear in the range 5 pmol-5nmol with a practical detection limit of 2 pmol. The assay coefficients of variation (n = 5) at 200 pmol for delta Di-HA and delta Di-0S were 1.7 and 1.5%, respectively. This HPLC system has been applied to the determination of HA in human urine. PMID- 1742548 TI - Determination and purification of metallothioneins by high performance liquid chromatography. AB - A rapid, reproducible and sensitive high performance liquid chromatography (HPLC) method for the determination and purification of metallothionein-I (MT-I) and metallothionein-II (MT-II) in mouse and rabbit livers has been developed. Methallothioneins (MTs) were separated by an HPLC anion exchange column, eluted through a linear gradient of Tris buffer and the peak containing MTs was determined by atomic absorption spectrophotometry. Furthermore, the content of MT I or MT-II was calculated by protein peak area in a short time (about 20 min). The sample to be tested was homogenized, centrifuged and saturated by cadmium. MT I and MT-II were eluted at 15.9 and 19.3 min, respectively. The following mouse liver cytosols were tested: controls, Cd-injected samples and 60Co-irradiated samples. A detection limit of 5 micrograms/g liver was established for this method. We have analysed more than 100 biological samples and obtained satisfactory results. PMID- 1742549 TI - Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations in young women as determined using high performance liquid chromatography. AB - Plasma B-6 vitamer and plasma and urinary 4-pyridoxic acid concentrations of 21 young white women, 21-27 years, having radiomonitored pyridoxal 5'-phosphate and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate vitamin B-6 status were determined in an effort to establish normal ranges for plasma B-6 vitamers. B-6 vitamers and 4-pyridoxic acid were quantitated using reversed phase high performance liquid chromatography with fluorometric and ultraviolet detection. Pyridoxal phosphate values obtained by radioenzymatic and chromatographic, fluorometric and ultraviolet, assays were highly correlated as were pyridoxine phosphate values determined using both detectors. The B-6 vitamer and 4-pyridoxic acid values of these subjects should be of use in the establishment of normal ranges of these congeners in women. PMID- 1742550 TI - Determination of short-chain fatty acids in equine caecal liquor by ion exchange high performance liquid chromatography after solid phase extraction. AB - A high performance liquid chromatography (HPLC) method was developed for the determination of seven short-chain fatty acids in equine caecal liquor. Samples were cleaned up on a Sep-pak (C18) cartridge, and the analyte was eluted from the extraction cartridge and filtered through a 0.45 micron cellulose nitrate filter. The analyte was chromatographed by ion exchange HPLC. Detection was by UV at 210 nm. Recovery from phosphate buffer (0.05 M, pH 7.0) and equine caecal liquor was 76.95% (lactic), 76.76% (valeric). The limit of (propionic), 89.35% (isobutyric), 88.73% (butyric), 80.33% (isovaleric) and 72.61% (valeric). The limit of detection of the short-chain fatty acids in phosphate buffer was 0.00006 M (lactic), 0.0001 M (acetic), 0.0002 M (propionic), 0.0001 M (isobutyric), 0.0002 M (butyric), 0.0002 M (isovaleric) and 0.0003 M (valeric). The specificity and sensitivity of this method was sufficiently high to allow the characterization of the pattern of these short-chain fatty acids in equine caecal liquor following intravenous administration of oxytetracycline at the recommended dose rate in a pony. PMID- 1742551 TI - Comparative performance of ion exchange and ion-paired reversed phase high performance liquid chromatography for the determination of nucleotides in biological samples. AB - We have compared anion exchange chromatography on APS-Hypersil (4.6 x 100 mm) eluted with a phosphate gradient with reversed phase chromatography on ODS Hypersil (4.6 x 100 mm) in the presence of either tetrabutylammonium (TBA) or triethylammonium (TEA) ions with a methanol gradient. The systems have been compared both for ease of operation and for their resolving power with standard mixtures and acid extracts of both normal red cells (RBC) and ischaemic tissues. The two chromatographic modes exhibited similar separating efficiencies for standard mixtures of nucleotides but retention times were most stable using reversed phase liquid chromatography (RPLC) with TEA. Anion exchange columns slowly lost ion exchange capacity but selectivity was unchanged. RPLC in the presence of TBA gave reproducibile capacity factors only when operated isocratically due to irreversible changes to the silica surface. For RBCs the RPLC with TEA and anion exchange systems resolved 17 and 15 peaks, respectively, and for the ischaemic samples 22 and 14 peaks, respectively. However, nucleosides and bases were also resolved by the ODS column causing chromatographic crowding and uncertain peak identification. PMID- 1742552 TI - Solid phase extraction of oxcarbazepine and its metabolites from plasma for analysis by high performance liquid chromatography. AB - A rapid, sensitive and simple-to-operate high performance liquid chromatographic method for the simulataneous determination of oxcarbazepine, 10 hydroxycarbazepine and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine in plasma is described. The drug and its metabolites were extracted from plasma using commercially available reversed phase octadecylsilane bonded-silica columns (Bond Elut C18, 1 mL capacity). Chromatographic separation of oxcarbazepine and its metabolites was achieved using a mobile phase consisting of acetonitrile/methanol/water (13:25:62 by volume) at a flow rate of 1.2 mL/min in conjunction with a Waters Associates Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a LiChrospher 5 microns C18 guard column. By measuring the UV absorbance at 214 nm, plasma levels in the region of 50-100 ng/mL for the drug and its metabolites can be detected with only 100 microL of plasma. The method has been applied to pharmacokinetic studies of oxcarbazepine and its metabolites in children with epilepsy; preliminary pharmacokinetic findings in two patients at steady-state are presented. PMID- 1742553 TI - Automated quantitative microcolumn chromatography of haemoglobin A2. AB - Automated cation exchange microcolumn chromatography of haemoglobins has been modified for the analysis of haemoglobin A2. It provides the quantitative data of sufficient precision and specificity for the investigation of potential heterozygotes for beta-thalassaemia. Results have been compared with an established method of electrophoresis followed by densitometry of the eluted bands. PMID- 1742554 TI - Liver high performance liquid chromatographic porphyrin profiles in experimental porphyria induced by peroxidizing herbicides. AB - The effect of peroxidizing herbicides on the liver porphyrin content of experimental animals was examined. Mice treated with the herbicide oxadiazon accumulated uroporphyrin and protoporphyrin in the liver. Formesafen-treated mice accumulated uroporphyrin and heptacarboxylic porphyrin. PMID- 1742555 TI - Results of speech perception and speech production training for three prelingually deaf patients using a multiple-electrode cochlear implant. AB - Five studies were conducted to measure changes in the perception and production of selected speech targets, with training, in three prelingually deaf patients. The two adults and one adolescent were implanted with the Cochlear (Nucleus) multiple-electrode prosthesis. The studies were perception and production of nasal consonants; perception of syllable-final consonants; perception and production of alveolar consonants; auditory-visual perception of alveolar consonants; and perception and production of vowels. Perceptual data were collected in the audition (implant)-alone condition, except for the auditory visual perception of alveolar consonants where the audition-alone, vision-alone, and auditory-visual conditions were used. Speech perception data in the audition alone condition were also collected from four postlingually deaf adult implant patients, without training, to indicate differences between the two classes of patients. The three prelingually deaf patients generally showed some improvements in speech production. In perception, improvements were recorded only for individual patients in some studies. The performance of the adolescent was better than that of the two adults in all cases. The perceptual performance of the postlingually deaf patients was superior to that of the prelingually deaf patients in all cases. PMID- 1742556 TI - The influence of eye colour on susceptibility to TTS in humans. AB - In order to investigate the function of the inner ear melanin, noise-induced temporary hearing loss (temporary threshold shift, TTS) was studied in humans with either blue or brown iris colour. Sixty-eight normally hearing teenage boys participated in this study. Hearing thresholds before and after exposure were established with a computerized sweep frequency audiometer in the frequency range 0.8-8 kHz. The noise exposure consisted of a 1/3 octave band-filtered noise with centre frequency 2 kHz at 105 dB SPL for 10 min. The mean TTS in the frequency range 2-8 kHz showed a significant difference with the brown-eyed subjects developing least TTS, and the blue-eyed subjects most TTS. PMID- 1742557 TI - Earmoulds: some benefits from horn fitting. AB - The narrow bore of conventional hearing aid earmoulds restricts the transmission of higher auditory frequencies. For subjects with moderate to severe high frequency hearing loss this is likely to have an adverse effect on the perception and recognition of phonemes with high-frequency components. Twenty-two subjects with predominantly high-frequency hearing loss underwent a series of tests to compare the performance of earmoulds having conventional 1.9 mm through-tubing with earmoulds fitted with a smooth horn with a final internal diameter of 4 mm. The test battery comprised free-field Bekesy audiometry, in-the-ear pressure measurement, speech audiometry using AB word lists and semantic differential rating of the relative sound quality of the two systems. Subjectively the horn fitting was rated as clearer, more natural, undistorted and acoustically comfortable. Objectively, by both Bekesy audiometry and in-the-ear pressure measurement, the horn gave more gain in the higher auditory frequencies. With the horn there was improved recognition of phonemes, especially fricatives and affricatives. PMID- 1742558 TI - A new toy test to investigate the hearing status of young children who have English as a second language: a preliminary report. AB - The aim of this study was to produce a word list suitable for children aged between 2 and 6 years with English as a second language (E2L) to be used in the format of a toy test to evaluate hearing status. Two lists of English words were compiled using words previously shown to be among the early English words learned by children from the Indian sub-continent. These word lists were evaluated in a group of 56 children who had recently arrived from Bangladesh. The results of this study yielded a final word list of 12 words, arranged into six pairs of words with matched vowels. This final word list, used in the E2L Toy Test, is currently being evaluated in a multi-centre study, for children between the ages of 3 and 6 years. PMID- 1742559 TI - A survey of New Zealanders with tinnitus. AB - A sample of 338 New Zealanders regularly experiencing tinnitus completed questionnaires posted to associations for people with tinnitus or hearing impairment. Nearly half the sample was sometimes depressed by tinnitus; those reporting depression and those reporting more severe problems as a consequence of their tinnitus saw more health-care professionals and used more coping strategies. Most respondents did not remember exactly when they first noticed their tinnitus; those that did reported a range of events that might have precipitated it. Respondents who sought medical help generally rated professionals as sympathetic, but few had been offered effective treatment. Comparison of the tinnitus sample with a sample of university students and staff indicated that though the respondents of the university sample often had some experience of tinnitus they reported sensations rather different from those of the tinnitus sample. PMID- 1742560 TI - Assessing hearing problems within a community survey. AB - Community surveys are increasingly being used as a method of collecting health and lifestyle data. This report describes the use of a simple question on hearing difficulties within such a survey. A systematic sample of 2.5% of the electoral register of the four Parliamentary constituencies of Cardiff, Wales, was drawn. Of the 5145 individuals in the sample, 83% responded. Age and social class explained much of the variability in reported hearing difficulties. A recent fall and cigarette consumption were associated with hearing problems, but the contribution of alcohol consumption while potentially important did not reach statistical significance. This self-administered community survey provided hearing data which are consistent with other specialized studies and is a viable route for the assessment of community needs. PMID- 1742561 TI - Extratympanic electrocochleography with a conductive fluid and flexible electrode. AB - Poor electrical stability of the recording electrode contact is often responsible for unstable recording conditions in extratympanic electrocochleography (ECochG). We present a new method with a large contact area formed by conductive fluid effectively penetrating the non-conductive film of wax and epidermis down to conductive tissue. The need for special cleaning of the external auditory meatus, often involving uncomfortable scratching of the sensitive area close to the tympanic membrane, has been eliminated, reducing the risk of infection and markedly improving the patient's test tolerance. Stable electrical contact improves the recording quality. We discuss a simplified clinical method, a new type of electrode, and patient risk factors as a result of possible accidental electrode movement. PMID- 1742562 TI - Prediction of hearing thresholds in children using an automated toy discrimination test. AB - A previous paper described the development of the prototype of a semi-automated, sensitive and accurate version of the McCormick Toy Discrimination Test. In this report we describe a further development of the hardware, and demonstrate that results obtained from the automated test provide a basis for estimating the mean elevation of pure-tone threshold in the child's better ear. The correlation between speech and pure-tone results is high. The average of the better ear pure tone thresholds at 0.5, 1 and 4 kHz can be predicted from the word-discrimination threshold obtained with the toy test, with a 95% confidence interval of +/- 11 dB. PMID- 1742563 TI - Lip-reading/speech-reading (LRD/SPR) for adults. A plea for individual assessment to decide upon appropriate method of assistance. PMID- 1742564 TI - Spontaneous and evoked otoacoustic emissions. PMID- 1742565 TI - IgA testing for diagnosis of retroviral infections in the Caribbean. AB - In Guadeloupe, a Caribbean island with a high prevalence of HTLV-I infected subjects, the percentage of false positive results for HIV IgG is high, requiring additional time and expense for confirmatory tests. This article describes a simple way of overcoming this problem. First, all IgG and IgG immune complexes are removed by protein G treatment, and then IgA enzyme-linked immunosorbent assay (ELISA) and the Western blot test are performed with minor modification of commercially available kits. PMID- 1742566 TI - Evaluation of newborn arm circumference as an indicator of low birth weight. AB - A sample of 1,024 newborns in Recife, Brazil, was studied to help determine the precision with which arem circumference measurements could be used to indicate low birth weight. The results support the view that when birth weight data are unobtainable, arm circumference measurements may be of value in screening for newborns needing special care. PMID- 1742567 TI - Behavioral response of Anopheles darlingi to DDT-sprayed house walls in Amazonia. AB - The behavioral response of Anopheles darlingi females to spraying of house walls with DDT was studied along the Ituxi River in Amazonas, Brazil, using a house sprayed with 2 g DDT per square meter of wall surface and an untreated house serving as a control. It was found that hardly any An. darlingi females entered, exited, or took blood meals inside the treated house after it was sprayed with DDT, and that specimens marked and released inside the house tended to depart immediately. This behavior appears to constitute true repellency rather than contact irritability. Since the typical house in the vicinity of the study site had only two walls, the persistence of malaria in the local area was probably due to home construction practices. PMID- 1742568 TI - Development of a registry for diabetes in persons 0-19 years of age in the U.S. Virgin Islands. AB - A juvenile-onset diabetes registry was recently established in the United States Virgin Islands. Hospital and clinic records were used as the primary sources of case data, while data procured through a physician survey and mass media campaign were used to assess the completeness and validity of the registry listings. The data indicated that 39 people 0-19 years old developed diabetes during the study period (1 January 1979-31 December 1988), of whom 36 probably had Type 1 diabetes. Completeness of the primary source data was estimated at 92.3% and validity seemed very good (around 100%). Evaluation of these registry data has provided new insights into the epidemiology of Type 1 diabetes in the U.S. Virgin Islands. PMID- 1742569 TI - Years of productive life lost to premature mortality from cardiovascular diseases. AB - Cardiovascular diseases exact a major toll in both developed and developing countries in terms of death, ill health, and premature incapacitation. This presentation concerns itself with the economic cost--expressed in terms of years of economically active life lost to premature mortality--imposed by cardiovascular diseases in relatively developed and undeveloped regions of Brazil. PMID- 1742570 TI - A program for prevention and control of epidemic dengue and dengue hemorrhagic fever in Puerto Rico and the U.S. Virgin Islands. AB - The ongoing resurgence of Aedes aegypti in the Americas--abetted by poor mosquito control, urbanization, and increased air travel--has led to dengue hyperendemicity, more frequent dengue epidemics, and the emergence of dengue hemorrhagic fever (DHF). This article describes a program developed to cope with this situation that emphasizes disease prevention rather than general mosquito control measures. PMID- 1742571 TI - Health damage caused by the smoking habit in Chile. AB - The authors review available literature on tobacco use in Chile, devoting particular attention to smoking prevalences, smoking-related health problems, risk factors that tend to encourage smoking, and appropriate control measures. Overall, the available data indicate that roughly 40% of Chile's adult population smokes, that smoking among women is on the rise, that some 11% of both infant and general mortality can be linked to tobacco use, that smoking during pregnancy poses serious health risks, and that the attitudes of physicians and other health workers can have a crucial impact upon the smoking behavior of their patients. PMID- 1742572 TI - Daniel Carrion and Carrion's disease. PMID- 1742573 TI - Cholera in the Americas. PMID- 1742574 TI - Risk of cholera transmission by foods. PMID- 1742575 TI - Status of new cholera vaccines. PMID- 1742576 TI - WHO reports on HIV and HBV transmission in the health care setting. PMID- 1742577 TI - British Society for Rheumatology. 8th annual general meeting. London, 18-20 September 1991. Abstracts. PMID- 1742578 TI - Quantitative computed tomography: comparative study using different scanners with two calibration phantoms. AB - To assess computed tomography (CT) scanners in vertebral quantitative computed tomography (QCT) measurement, five cadaveric vertebrae fixed in a water phantom were measured using 16 CT scanners of 10 different models using two types (CaCO3 and K2HPO4) of reference phantom. Although the same reference phantoms were used, the QCT values varied markedly depending on the CT scanner employed. The differences in QCT values were greater in the equivalent amount of CaCO3 than in that of K2HPO4. The largest difference between CT scanners was 40 mg/cm3 in the equivalent amount of CaCO3 and 28 mg/cm3 in that of K2HPO4. These differences were reflected among CT scanners by different slopes and intercepts of the reference lines of CaCO3, K2HPO4 and ash density depending on the CT scanner used. However, good correlations (r greater than 0.97) were observed for the QCT values obtained by various CT scanners. These results show that QCT values on one machine can be compared more closely with those of another machine if conversion formulae, determined by using materials equivalent to human vertebral bone, are employed. PMID- 1742579 TI - Initial investigation of childhood urinary tract infection: does the plain abdominal X ray still have a role? AB - To reassess the plain abdominal X ray (AXR) in the initial investigation of childhood urinary tract infection, radiologists from four paediatric units prospectively collected data on the yield from the AXR in 683 children. Five children had renal calculi. All were detected on ultrasound, but one was not visible on the initial AXR. Four spinal abnormalities were identified, none of which prompted any action by the clinician involved. While the costs, in both financial and radiation risk terms, may be small, the benefit of the AXR appears equally small. Where expert paediatric ultrasonography is available we would recommend that the AXR be reserved for patients with haematuria, loin pain, family history of calculus disease, or where further urinary tract infection occurs despite a normal ultrasound scan. PMID- 1742580 TI - Floating thrombi: diagnosis and follow-up by duplex ultrasound. AB - The clinical features and evolution of floating thrombi (FT) diagnosed by duplex ultrasound were examined. In 76 consecutively diagnosed above-knee deep venous thromboses the prevalence of FT was 18%. Of 44 FT diagnosed in 39 patients, 18 (39%) were located in the common femoral, 12 (26%) in the popliteal and seven (15%) in the external iliac veins. Serial duplex examinations revealed that 31% of FT in the iliofemoral segment disappeared 33% remained unchanged and 36% adhered to the vein wall within 2 weeks following diagnosis. After 3 months, 87% of the floating segments had disappeared, irrespective of the localization or therapeutic regimen. Thirteen patients experienced pulmonary embolism before (12/13) or following (4/13) diagnosis of floating thrombosis; three of four superficial femoral vein FT embolized. Fifteen per cent of the patients with FT died during the study period and 28% of the thrombi were associated with a malignant neoplasm; the incidence of malignancy was 60% in superficial and 39% in common femoral vein FT. PMID- 1742581 TI - Chest radiograph scoring system for use in pre-term infants. AB - A scoring system to characterize the pre-term infant's chest radiograph appearance has been evaluated. Chest radiographs taken at 1 month of age in 20 infants (median gestational age 27 weeks) were scored according to abnormalities of lung volume, presence of opacification, interstitial changes and cystic elements (maximum score 17). The median score was 4 (range 1-14); the highest scores were for the only infants with cystic elements and/or interstitial changes on their chest radiographs. The scoring system documented accurately the severity of neonatal respiratory distress; the highest scores occurred in those infants requiring the most prolonged respiratory support, i.e. ventilated beyond 1 week of age (p less than 0.01) and oxygen-dependent beyond 1 month (p less than 0.01). It was also a useful predictor of chronic respiratory problems, with an 88% sensitivity in the detection of infants with the most severe lung function abnormalities at 6 months of age. PMID- 1742582 TI - Computed tomography attenuation measurements for the characterization of hepatic haemangiomas. AB - The attenuation values of 21 hepatic haemangiomas in 19 patients were measured on non-enhanced computed tomographic (CT) scans and compared with the attenuation of adjacent liver and the inferior vena cava (IVC). The attenuation of hepatic haemangiomas was lower than that of the surrounding liver, but there was no correlation between these two measurements. There was a highly significant correlation between the attenuation of haemangiomas and blood in the vena cava (r = 0.905, p less than 0.001). All the haemangiomas had attenuations within 7 HU of caval blood. By comparison, in 34 hypodense hepatic lesions that did not show contrast-enhanced appearances characteristic of haemangioma, there was no significant correlation between the attenuation of the lesions and the IVC. Nineteen (56%) of these lesions had attenuations differing more than 7 HU from that of caval blood. The influence of this observation on the requirement for dynamic contrast-medium-enhanced and delayed post-contrast CT in the assessment of hepatic lesions is discussed. PMID- 1742583 TI - Comparative performance in vitro and in vivo of Lunar DPX and Hologic QDR-1000 dual energy X-ray absorptiometers. AB - The measured absolute bone mineral density values of spine and femur and their precision were compared on two dual energy X-ray absorptiometers, the Lunar DPX and the Hologic QDR-1000. There were systematic differences between the two systems, the Lunar DPX always giving a higher bone density value. The ratio of the mean Lunar DPX/Hologic QDR-1000 bone density measurements obtained in vivo was 1.13 g/cm2 for spine (L2-L4) and 1.20-1.43 g/cm2 for femur measurements. For both systems, short- and long-term precision (coefficient of variation) was below 0.5% for spine in vitro measurements and below 1.5% for neck of femur in vitro measurements. Precision of in vivo measurements was less good, especially for femur measurements. The coefficient of variation of spine measurements was dependent on bone density and deteriorated with decreased bone mineral density and increased body thickness. PMID- 1742584 TI - Registration of MR and CT images for skull base surgery using point-like anatomical features. AB - We have developed a registration technique for combining magnetic resonance imaging (MRI) and computed tomography (CT) images of the skull base for use in surgical planning. The technique is based on user identification of point-like landmarks visible in both modalities. The combination of images involves a small amount of expert interaction, is relatively quick and preliminary evaluation indicates that it is accurate to within 1.5 mm. Registered or fused images can be viewed either on an image processing workstation, or fused images can be printed onto conventional film for convenience in clinical use. We present one patient in order to demonstrate the technique's indications and advantages. PMID- 1742585 TI - Long term results of Cathetron high dose rate intracavitary radiotherapy in the treatment of carcinoma of the cervix. AB - Between 1967 and 1974, 371 patients with carcinoma of the cervix have been treated by a combination of external beam radiotherapy and fractionated high dose rate brachytherapy using the Cathetron. A retrospective review was undertaken in 1986 and median follow-up time was 6 years. Life table analysis of survival and complications to 16 years was undertaken. International Federation of Gynaecology and Obstetrics (FIGO) stage distribution was 26%, 46% and 28% for Stages I, II and III, respectively, and 5 year survival was likewise 94% 63% and 37%. Age and histological type or grade were not found to influence survival. Recurrent disease was recorded in 142 patients; the first site was within the pelvis in 25% and as distant metastases in 17%. Following development of pelvic recurrence median survival was 28 weeks. Salvage surgery was performed in 32 patients, of whom five probably obtained survival benefit. Significant late morbidity was seen in a total of 71 patients (19%); in seven patients this was at more than one site. Late morbidity to the small bowel was recorded as Grade 2 in 10 patients and Grade 3 in 13; to the rectum, Grade 2 in 10 patients and Grade 3 in two patients; to the bladder, Grade 2 in 15 patients and to the vagina Grade 2 in 29 patients. Median time to onset for small bowel morbidity was 14 months, for rectum 18 months, for vagina 20 months and for bladder 52 months. 82% of all late morbidity had been seen by 5 years of follow-up, no case of late morbidity of recurrence was seen between 11 and 18 years of follow-up. These results are comparable to those reported for other methods in use at the time the patients were treated. PMID- 1742586 TI - Treating the vaginal vault in carcinoma of the endometrium using the Buchler afterloading system. AB - The advent of high-dose-rate afterloading intracavitary radiotherapy has implications for both staff safety and the possibility of convenient, outpatient based treatment for the patient. We have carried out a retrospective analysis of its use with high-activity iridium 192 and the Buchler machine to treat the vaginal valut in patients with adenocarcinoma of the endometrium, most of whom also received external-beam radiotherapy to the pelvis. We have compared the survival, complication and local control rates with a comparable group of historical controls treated with low-dose-rate intracavitary caesium ovoids. Complication rates, which included vaginal stenosis not volunteered by the patient, were 16% (95% confidence intervals 6-26%) in the study group and 28% (95% confidence intervals 17-41%) in the control group, with no serious complications requiring surgery. The actuarial survival was 92% at 5 years in the study group, and 94% at 5 years in the control group. Local control was 94% at 5 years in the control group and 98% at 5 years in the study group. The authors suggest that the use of high-dose-rate intracavitary radiotherapy, with the Buchler afterloading system, for vaginal vault irradiation in carcinoma of the endometrium is a convenient, safe and quick method, which does not necessitate admission or sedation of the patient. In addition it provides complete radiation protection for staff. PMID- 1742587 TI - A phantom for the measurement of contrast detail performance in film-screen mammography. AB - A National Breast Cancer Screening Programme, based on X-ray mammography, has been introduced in the UK. The success of this screening programme is dependent on the production of high quality radiographs. There are various methods of assessing imaging performance in mammography, but contrast detail detectability measurements have an advantage in that the observation of radiographs is taken into consideration. The design and construction of a contrast detail phantom for the assessment of image quality in mammography is described. This phantom can be used to assess the imaging performance of mammographic film-screen combinations. The results of some measurements to verify the accuracy of the contrast predictions are presented together with some initial results of an investigation into the contrast detail performance of film-screen combinations used in mammography. PMID- 1742588 TI - Three-dimensional (3D) ultrasound imaging of the gallbladder and dilated biliary tree: reconstruction from real-time B-scans. PMID- 1742589 TI - Neonatal hepatic calcification in subcapsular haematoma with hydrops fetalis. PMID- 1742590 TI - Oesophageal ruptures complicating balloon dilatation of strictures: a report of two cases. PMID- 1742591 TI - Relapsing polychondritis: report of an unusual case and a review of the literature. PMID- 1742592 TI - Thorium dioxide, forgotten but not gone. PMID- 1742593 TI - Radiological manifestation of elastofibroma: a case report and review of the literature. PMID- 1742594 TI - Nitrous oxide--radiosensitizer or radioprotector? PMID- 1742595 TI - Percutaneous femoral artery puncture: practice and anatomy. PMID- 1742596 TI - How and why are ultrasonic scanners chosen? PMID- 1742597 TI - Cholangiography in liver transplantation: a comparison of two types of biliary reconstruction. AB - Orthotopic liver transplantation has been performed in Birmingham since 1982. Two types of biliary reconstruction have been used, the choledocho-choledochostomy and the choledocho-cholecysto-choledochostomy (gallbladder (GB) conduit). A retrospective study was undertaken to compare the biliary tract complications encountered at cholangiography in these two groups to assess which reconstruction is safest. In the gallbladder (GB) conduit reconstruction, the incidence of biliary leakage (20.4%) and stricture formation (14.4%), the two most serious complications, was higher than in end-to-end duct anastomosis (11% and 10%, respectively), though these differences did not reach statistical significance. This supports evidence from other centres that the choledocho-choledochostomy is the procedure of choice to minimize biliary complications. Biliary debris (14.2%) presented additional problems and was strongly associated with biliary strictures. T-tube related problems were least troublesome. The close relationship between hepatic artery occlusion and biliary complications, particularly leakage, noted in other studies is also emphasized. PMID- 1742598 TI - Low-frequency sensitivity in a gerbilline rodent, Pachyuromys duprasi. AB - The contribution of the bulla to low-frequency hearing capability was studied in the gerbilline rodent Pachyuromys duprasi. In the frequency range of 0.6-3 kHz, the sound pressure behind the tympanic membrane is higher than the pressure in the meatus acusticus externus near the eardrum. Gradual augmentation of frequencies above 0.6 kHz gives rise to steadily increasing phase lag in the bulla relative to that in the meatus. Severing of the incudostapedial joint yields results indicating that the phase difference between meatus and bulla is caused by resonance properties of the bulla and resistance in the cochlea. Both destruction of the bulla and stiffening of the pars flaccida tympani lead to a sound pressure decrease in the frequency range around 2 kHz. This drop is accompanied by an amplitude decrease of the same magnitude in the cochlear microphonic potentials. These results support the hypothesis that the bulla functions like a Helmholtz resonator in the frequency range of 1-3 kHz, improving sound transduction to the cochlea. These experimental findings, in conjunction with theoretical considerations involving bulla volume, orifice area of the resonator, and resonance frequency of the bulla, suggest that the theoretically required area of the resonator's orifice is, in fact, of the same magnitude as the area of the pars flaccida tympani. The middle-ear system of P. duprasi thus consists of a resonating bulla in which the area of the pars flaccida tympani constitutes the resonator's opening towards the meatus and in which the pars tensa tympani functions as a pressure gradient receiver, due to phase differences caused by the resistance of the cochlea and by the resonance properties of the bulla. By these functional principles the peripheral auditory system of P. duprasi is capable of low-frequency perception despite the smallness of its structures. The middle ear in P. duprasi thus represents a prime example of a strategy: the dimensional constraints derived from a general bauplan for the peripheral auditory system have here been overcome. PMID- 1742599 TI - Retinal projections in the freshwater butterfly fish, Pantodon buchholzi (Osteoglossoidei). I. Cytoarchitectonic analysis and primary visual pathways. AB - The freshwater butterfly fish, Pantodon buchholzi, is a member of the most primitive radiation of teleosts. The retinofugal projections were studied in this fish with autoradiographic and horseradish peroxidase (HRP) methods, and the cytoarchitecture of the retinorecipient regions in the diencephalon and pretectum was analyzed with Bodian-, cresylecht-violet- and acetylcholinesterase-reacted sections. The rostral diencephalon of Pantodon contains a large retinorecipient nucleus, not previously identified in any other fish, i.e. nucleus rostrolateralis. Other nuclei that are described correspond to those previously recognized in other species. The majority of retinorecipient nuclei are positive for acetylcholinesterase, particularly those in the pretectum, as has been found in other species of teleosts. Most of the retinofugal fibers decussate in the optic chiasm. Some fibers project via the axial optic tract to preoptic nuclei and a region in the rostral hypothalamus. Fibers leave the medial optic tract to terminate in nucleus rostrolateralis and in dorsal and ventral thalamic nuclei, accessory optic and tubercular nuclei, periventricular and central pretectal nuclei, and sparsely in the deep tectal fascicle and terminal field. Dorsal optic tract fibers project to the dorsal accessory optic nucleus, superficial and central pretectal nuclei, and superficial and deep tectal layers. Ventral optic tract fibers project to the superficial pretectum, accessory optic nuclei, posterior tuberculum, nucleus corticalis in the central pretectum, and superficial tectal layer. Fibers that remain in the ipsilateral optic tract project to most of the targets reached by contralaterally projecting fibers. A few fibers in the contralateral medial optic tract redecussate via the posterior commissure to reach the ipsilateral periventricular pretectum. No labeled retinopetal cells caudal to the olfactory bulb were identified in any of the HRP cases. PMID- 1742600 TI - Retinal projections in the freshwater butterfly fish, Pantodon buchholzi (Osteoglossoidei). II. Differential projections of the dorsal and ventral hemiretinas. AB - Pantodon buchholzi, the freshwater butterfly fish, is a member of the Osteoglossomorpha, the most primitive of the four major teleost radiations. The projections of fibers originating in the dorsal and ventral hemiretinas in Pantodon, as determined with autoradiography, are reported here. Fibers originating in the ventral hemiretina reach their targets through the axial, medial and dorsal optic tracts. Fibers that originate in the dorsal hemiretina reach their points of termination by way of the axial, medial and ventral optic tracts. Projections of the various tracts to preoptic, thalamic, tubercular, pretectal and tectal regions, as described in the previous study of total retinal projections, were verified. The retinal projections to the preoptic, thalamic and tubercular nuclei do not map topographically. Ventral hemiretinal fibers are mapped, however, onto the dorsal part of the nucleus pretectalis superficialis pars parvocellularis, the rostral part of the dorsal accessory optic nucleus, the entire nucleus pretectalis periventricularis pars ventralis and the dorsomedial portion of the optic tectum. Ventral hemiretinal fibers also supply most if not all the retinal innervation to the central pretectal nucleus. In contrast, dorsal hemiretinal fibers are mapped onto the ventral part of nucleus pretectalis superficialis pars parvocellularis, the entire dorsal accessory optic nucleus and the ventrolateral portion of the optic tectum. The dorsal and ventral hemiretinal projections to the tectum about at a cytoarchitectonically recognizable point, indicating that no discontinuity is present in the retinal connectivity with the tectum. The pars parvocellularis of nucleus pretectalis superficialis is a simple, unfolded, and nonlaminar structure in Pantodon. This structure contrasts markedly with the more complex, folded structure of the nucleus in the majority of other examined teleosts. The orientation of the projections from the dorsal and ventral hemiretinas onto this nucleus in Pantodon is congruent with that seen in other fishes only after a schematic unfolding of the nucleus in these fishes. PMID- 1742601 TI - Comparative cytoarchitectonic analysis of some visual pretectal nuclei in teleosts. AB - The posterior pretectal nucleus, which in Osteoglossum receives second order visual input and projects to the inferior lobe of the hypothalamus, was identified and characterized in species from all major groups of non-neoteleost teleosts. The hypothesis that the posterior pretectal nucleus in these species is homologous to both the pars intermedius of the superficial pretectal nucleus and nucleus glomerulosus in acanthopterygians is supported by multiple similarities in relative position and cytoarchitecture. Nucleus corticalis, which receives retinal input and projects to the posterior pretectal nucleus (or to nucleus glomerulosus), was identified in species belonging to three of the four major teleost radiations. Both the posterior pretectal nucleus and nucleus corticalis are plesiomorphic for teleosts. The presence of glomeruli in the posterior pretectal nucleus and nucleus glomerulosus in esocids and acanthopterygians, respectively, and the presence of two nuclei, the pars intermedius and nucleus glomerulosus, in acanthopterygians, as opposed to one nucleus, the posterior pretectal nucleus, are apomorphies. PMID- 1742602 TI - Isolation of a rat S100 alpha cDNA and distribution of its mRNA in rat tissues. AB - In order to clarify the reported discrepancies in S100 alpha protein and mRNA distribution in rat tissues, a rat S100 alpha cDNA has been isolated and this species homologous probe along with a rat S100 beta cDNA probe has been used to examine S100 mRNA expression in rat tissues. Although the rat S100 alpha cDNA was missing approximately 30 nucleotides of coding sequence, only 4 conservative changes in amino acid sequence were observed when the deduced amino acid sequence was compared to the bovine S100 alpha amino acid sequence. Thus, S100 alpha proteins, like S100 beta proteins, are highly conserved among species. All nineteen of the tissues examined (including cerebrum and cerebellum) contained S100 alpha mRNA. In addition, S100 beta mRNA was detected in thirteen of the nineteen tissues examined. These results are in agreement with previous protein distribution studies and further demonstrate that S100 proteins are not brain specific and are expressed in a large number of tissues. Although S100 alpha and S100 beta mRNAs were detected in rat tissues which had previously been reported to contain S100 alpha and S100 beta protein, a direct correlation between the protein and mRNA levels were not observed, suggesting that different mechanisms regulate S100 expression in various tissues. S100 alpha exhibited a single similar size mRNA species (0.5 Kb) in all tissues examined, as did S100 beta (1.5 Kb), suggesting that the individual S100 proteins are expressed as single mRNA and protein products in rat tissues. PMID- 1742603 TI - Nucleus A10 dopaminergic neurons in inbred mouse strains: firing rate and autoreceptor sensitivity are independent of the number of cells in the nucleus. AB - Inbred mouse strains have different numbers of midbrain dopaminergic neurons; for example, BALB/cJ mice have 20-25% more neurons than CBA/J mice. As the number of cells decrease, for example in Parkinson's disease and in animals with midbrain dopaminergic cell lesions, the activity of their remaining cells increases. The purpose of the present experiment was to determine whether the functional properties of dopaminergic neurons in the ventral tegmental area (nucleus A10) differ in inbred mouse strains which possess different numbers of cells. The firing rate and autoreceptor sensitivity of A10 dopaminergic cells were examined in the in vitro slice preparation in BALB/cJ, C3H/HeJ, CBA/J, and DBA/2J mouse strains. It was observed that the autoreceptors on mouse dopaminergic neurons exhibit pharmacological properties of dopamine autoreceptors; activation of the autoreceptor produced a marked inhibition (50-70%) in cell firing rate by quinpirole (10(-8) M), LY-141865 (10(-7) M), (+)-3-(3-hydroxyphenyl)-N-n-propyl piperidine (10(-6) M), propyl-norapomorphine (10(-5) M) and dopamine (10(-4) M), and this inhibition was blocked or reversed by specific dopamine D2 receptor antagonists [(-) sulpiride and spiroperidol, 10(-6) M]. The baseline firing rates of the A10 cells did not differ among the four inbred strains [range 2.5 +/- 0.2 (C3H/HeJ)-3.4 +/- 0.3 (CBA/J) spikes/s +/- SEM], and there was no significant difference in autoreceptor sensitivity among the mouse strains as assessed either by superfused dopamine (inhibitory dose 50% approximately 150 microM), or by superfused quinpirole (inhibitory dose 50% approximately 10 nM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742604 TI - Biogenic amine localization in cardiac ganglion intrinsic neurons: electron microscopic histochemistry of SIF cells. AB - The parasympathetic cardiac ganglion in the mudpuppy, N. maculosus, contains postganglionic nerve cells and intrinsic neurons, many of which are small intensely fluorescent (SIF) cells. Several bioactive substances have been localized in the intrinsic nerve cells which may have integrative effects at synapses within the ganglion. Ganglionic intrinsic neurons can be identified electron microscopically by the presence of numerous cytoplasmic granular vesicles 80-120 nm in diameter. Throughout the ganglion there are bundles of unmyelinated fibers some of which are filled with granular and agranular vesicles and axosomatic terminals with similar vesicles synapsing on principal parasympathetic nerve cells. To understand the aminergic contribution to ganglionic synaptic circuitry the chromaffin reaction was used. The intrinsic neurons (i.e., SIF cells) were readily identified by their characteristic intracellular granule population. All intrinsic nerve cells identified showed granules which were positively labelled by the chromaffin reaction. Granular vesicles in synaptic profiles on principal cells (P cells) were also labelled indicating a direct aminergic synaptic innervation to these cells. The cell bodies of intrinsic neurons, ensheathed with supportive glial-like cellular processes, rarely received synapses. Elemental microanalysis was used to verify the chromium content of the electron dense product within the granular vesicles. These studies demonstrated direct aminergic synaptic input to at least a subpopulation of principal parasympathetic cells in the cardiac ganglion of mudpuppy. PMID- 1742605 TI - Effect of melatonin replacement on serum hormone rhythms in a patient lacking endogenous melatonin. AB - A potentially confounding variable inherent in studies designed to examine the effect of melatonin administration in humans is the presence of an endogenous melatonin rhythm in the experimental subjects. The effects of exogenous melatonin administration on serum hormone rhythms was recently examined in a male patient who lacked detectable circulating levels of endogenous melatonin. The patient's pineal gland had been destroyed five years previously in the course of treatment for a pineal astrocytoma. On three separate occasions, over approximately a one year period, the patient was given daily oral melatonin replacement (2 mg/day, 1 mg/day and 0.5 mg/day). These experiments were designed to assess the effects of exogenous melatonin on serum growth hormone, prolactin, cortisol and testosterone rhythms. Analysis of blood samples collected every 2-4 hours periods both before and during melatonin replacement revealed that the exogenous melatonin rhythm was associated with improvements in self-reported sleep and mood ratings. Melatonin administration produced robust nocturnal peaks in serum growth hormone and prolactin levels immediately following ingestion of the hormone, while serum cortisol and testosterone rhythms were not influenced. These results suggest that melatonin may modulate the coordination and enhancement of selected biological rhythms in man. PMID- 1742606 TI - Identification of a mouse brain beta-spectrin cDNA and distribution of its mRNA in adult tissues. AB - A mouse brain beta-spectrin of cDNA was identified within a lambda Gt11 expression library using an antibody which specifically binds with the 235 kDa spectrin beta-subunit. Restriction mapping and DNA sequencing analyses of the brain cDNA revealed that this clone contained 1185 bp of sequence, of which a 999 bp single open reading frame encoding 333 amino acids was determined. The deduced amino acid sequence exhibited homology with beta-spectrins, demonstrating the characteristic 106 amino acid repeating unit. The homology between our mouse brain sequence and human RBC beta-spectrin was approximately 56% beginning at the beta 15 repeat unit and extending to the C-terminus of sequence elucidated for human RBC sequence. An additional 62 amino acids were found at the C-terminus of the 235 kDa brain beta-spectrin subunit not seen in the human RBC sequence. The approximately 1.2 Kb brain spectrin cDNA insert hybridized with a single 9 Kb mRNA transcript in various adult mouse tissues, with the most abundant hybridization demonstrated in RNA isolated from brain tissue. This mRNA was found to be present at high levels in heart tissue and at lower levels in spleen and skeletal muscle tissue. The 9 Kb mRNA was different in content and in size to mRNAs which hybridized with a cDNA encoding the mouse erythroid beta-spectrin subunit, demonstrating that the brain spectrin cDNA is a distinct gene product and represents the first known sequence of a nonerythroid beta-spectrin subunit. PMID- 1742607 TI - The effect of synapsin I phosphorylation upon binding of synaptic vesicles to spectrin. AB - We have previously demonstrated that brain spectrin is attached to small spherical synaptic vesicles via synapsin I. These studies utilized a novel microfiltration assay in which 125I-labelled synaptic vesicles were incubated with brain spectrin which was covalently attached to cellulosic membranes. In these studies purified dephosphosynapsin I was demonstrated to competitively inhibit the binding of the synaptic vesicles to the immobilized brain spectrin with a KI = 45 nM. In the current study we demonstrate that phosphorylation of synapsin I site 1 (0.74 mol Pi/mol synapsin I) with cAMP-dependent protein kinase and sites 2 and 3 (2.0 mol Pi/mol synapsin I) with Ca(2+)-calmodulin kinase II had little effect upon its interaction with brain spectrin. cAMP-dependent protein kinase phosphorylated synapsin I and Ca(2+)-calmodulin kinase II phosphorylated synapsin I both inhibited the binding of 125I-labelled synaptic vesicles to immobilized brain spectrin with a KI of 23 nM and 24 nM respectively. We conclude that phosphorylation of synapsin I does not down-regulate the interaction of synaptic vesicles with brain spectrin. PMID- 1742608 TI - Comparison of the effects of acute and chronic ibotenic and quisqualic acid nucleus basalis lesioning. AB - The present study examines the effects of acute (1 month recovery) and chronic (8 month recovery) bilateral quisqualic (quis) and ibotenic (ibo) acid nucleus basalis (NB) lesioning on the activity of cholinergic neurons and on passive avoidance (PA) and water-maze (WM) performance. Our data demonstrate that A: The activity of choline acetyltransferase (ChAT) in cortical tissue and the number of ChAT positive neurons in the NB were decreased 1 and 8 months after quis or ibo NB lesioning. B: Ibo NB lesioning produced a greater nonspecific subcortical cell loss than quis NB lesioning. C: PA retention was impaired by acute and chronic quis and ibo NB lesioning. D: Acute ibo NB lesioning impaired acquisition and reversal learning in WM performance whereas chronic ibo NB lesioning impaired only reversal WM learning. Acute and chronic quis NB lesioning impaired reversal WM learning. The present results suggest that NB cholinergic neurons do not recover spontaneously from excitotoxin-induced damage and that they may be importantly involved in inhibitory avoidance and spatial reversal learning performance. PMID- 1742609 TI - Restraint and stimulation of bed nucleus of the stria terminalis produce similar stress-like behaviors. AB - Restraint stress, electrical stimulation of the bed nucleus of the stria terminalis (BNST), and the combination of restraint stress and BNST stimulation were studied using a computerized animal activity monitoring system. Both restraint and the combination of restraint and BNST stimulation produced increases in locomotor, exploratory and stereotypic activity all of which returned to baseline within an hour while BNST stimulation alone also increased measurements of locomotor and exploratory behavior some of which remained elevated throughout the three-hour period of measurement. BNST stimulation also produced vigorous escape behavior and biting which were not seen with restraint alone. Thus electrical stimulation of BNST produces behavior which is qualitatively similar to the behavior produced by stress but differs in time course. PMID- 1742610 TI - Nigrostriatal dopaminergic cell activity is under control by substantia nigra of the contralateral brain side: electrophysiological evidence. AB - The biochemical balance between right- and left-ascending DA systems is an essential factor to regulate behavioral lateralization. However, there is no electrophysiological evidence for the regulation of interhemispheric DA systems. In the present paper we report electrophysiological evidence supporting the hypothesis that the A9 DA cells are under control of the contralateral substantia nigra. The activity of more than 80% of the A9 cells recorded was affected by contralateral SN stimulation. This is a very high proportion because the previously reported response of A9 cells to ipsilateral caudate stimulation is proportionally lower. The potency of a stimulus, estimated as the number of action potentials induced or inhibited by each electrical stimulation of the contralateral substantia nigra or by the percentage of modification in the number of action potentials induced or inhibited in relation to the spontaneous potential expected, was also high. The response to the contralateral stimulation was complex. Fifty-four percent of all the DA cells studied showed more than a single response. Forty-four percent showed at least one stimulation and at least one inhibition. Because 1) the percentage of cells with at least one stimulation (70%) was higher than the percentage of cells with at least one inhibition (56%), and 2) the potency of stimulations was higher than the inhibition potency, the present data provide evidence that contralateral control of A9 cells is mainly excitatory. The percentage of cells activated by contralateral stimulation was high, between 30 ms and 220 ms and between 400 ms and 700 ms. The probability of inhibition was higher than the probability of activation between 10 ms and 30 ms and between 230 and 380 ms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742611 TI - Contrasting effects of stress on medial and sulcal prefrontal cortex self stimulation. AB - Male Wistar rats were subjected to either 25 controllable or uncontrollable footshocks and then tested for changes in fixed-interval 5-second (FI-5) self stimulation of the medial prefrontal cortex (MPC), sulcal prefrontal cortex (SPC) or nucleus accumbens (NAS). Controllable footshock caused a moderate facilitation of MPC self-stimulation (30% above baseline rates) but inhibited SPC self stimulation (32% below baseline rates). Uncontrollable footshock had no effect on MPC self-stimulation but inhibited SPC self-stimulation (52% below baseline rates). An inhibition of SPC self-stimulation was also evident 24 hours following controllable or uncontrollable footshock. NAS self-stimulation was unaffected by footshock. Changes in locomotor activity were not consistently related to changes in self-stimulation following footshock. These results are discussed in terms of the different effects of mild stress on the release of reward-relevant neurotransmitters in the MPC, SPC and NAS. The possible role of stress-induced hypoalgesia in determining the stress-induced facilitation of MPC self stimulation is also discussed. PMID- 1742612 TI - Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees. AB - We have systematically investigated the involvement of endogenous opioids in gonadotropin secretion during primate sexual maturation by examining LH/FSH responses to gonadotropin-releasing hormone (GnRH) and changes in LH secretion during infusions of saline or naloxone, an opiate antagonist, in ten male chimpanzees between one and nine years of age. Animals were anesthetized with ketamine (10 mg/kg) and injected or infused IV with GnRH, naloxone or saline. Circulating levels of serum LH were elevated to the same extent (approximately 400%) in response to GnRH (100 micrograms) in animals 1-5 years old (juvenile) and in animals 6-9 years old (pubertal). No differences were noted between the two groups in GnRH-stimulated levels of serum FSH. During treatment with naloxone (0.14 mg/kg bolus followed by 0.2 mg/kg/h maintenance infusion for 3 h), serum LH levels in pubertal animals were significantly (p less than 0.05) elevated by as much as 95% over LH levels found during treatment with saline. Juvenile animals, on the other hand, failed to demonstrate significant increases in serum LH following naloxone at the doses tested. A strong correlation (r = .84) was found between circulating testosterone and serum LH levels during naloxone treatment. These data indicate that opioid inhibition of LH secretion can be reversed by naloxone only when puberty is reached in chimpanzees and suggest an alteration in opioid regulation of GnRH near the time of puberty. The strong correlation between testosterone levels and LH responses to naloxone suggests that steroids may participate in the maturation of opioid control of LH during puberty of nonhuman primates. PMID- 1742613 TI - Chronic Ro 15-1788 treatment increases REM sleep in rats. AB - Administration of Ro 15-1788, a benzodiazepine antagonist (3.6 mg/kg/day in drinking water for 14 days), increased total sleep and rapid eye movement (REM) sleep in rats. Standard six-hour EEG recording periods were obtained on day 0, 1, 3, 7, 10, 14, as well as 24 and 72 hours following withdrawal. Enhanced REM sleep reached significance on day 7 of continuous drug treatment and remained significantly increased on day 10 and 14, as well as at 24 and 72 hours following drug withdrawal. The present data show that chronic administration of Ro 15-1788 increases total sleep time due to increases in REM sleep. The actions of Ro 15 1788 presumably occur through either adenosinergic or cholinergic mechanisms. PMID- 1742614 TI - Anterograde neuroanatomical tract tracing with central nervous system injections of immunoglobulin G: a light and electron microscopic evaluation. AB - Normal rabbit serum (NRS) was pressure injected into the forebrain of rats to be tested as an anterograde neuroanatomical tracing substance. Undiluted NRS was stereotaxically injected into the bed nucleus of the stria terminalis (BST) with a 1-microliter Hamilton syringe. Postinjection survival times ranged from 24 h to 14 days. An immunohistochemical method utilizing goat anti-rabbit IgG antibody was used to detect the rabbit IgG within vibratome sections. Visualization of the final reaction product (diaminobenzidine, DAB) was enhanced by a silver/gold postintensification (SGI) method. Rabbit IgG-containing neural structures were examined at both light and electron microscopic (EM) levels. At the injection site neuronal soma, dendrites and axons were filled homogeneously with the SGI DAB at 24 h, 48 h, 7 days and 14 days indicating local neuronal uptake, storage and transport of rabbit IgG. In the hypothalamus many anterogradely filled axons were present and displayed short collateral branches and terminals. EM examination revealed synaptic terminals containing IgG, without signs of transsynaptic transport after 14 days. Signs of retrograde transport of IgG were never observed. A propensity of neurons to take up, sequester and anterogradely transport immunoglobulin G is indicated. PMID- 1742615 TI - Lateralized action of androgen on development of behavior and brain sex differences. AB - Androgens have been linked to asymmetric brain development. Our results show that in sexually active male gerbils, the volume of the sexually dimorphic area, pars compacta (SDApc) of the preoptic region was positively correlated with the emission rate of an ultrasonic courtship vocalization. Day 1 postnatal treatment of female gerbils with testosterone propionate (TP, 100 micrograms, n = 16) or diethylstilbestrol (DES, 5 micrograms, n = 22) followed by ovariectomy and implantation of testosterone (T) filled silastic capsules in adulthood (day 120 130), increased mean volumes of the SDApc (TP, 1.21: DES, 0.84 mm3 x 10(-3)) and a second sexually dimorphic nucleus, the suprachiasmatic nucleus (SCN) (TP, 295: DES, 287.7 mm3 x 10(-3] compared to control females (n = 13) also given T in adulthood (SDApc = 0.37, SCN = 197.0 mm3 x 10(-3)). Rates of sexually dimorphic ultrasonic calls emitted during sexual interactions with estrous females (TP, 39.3: DES, 28.1 per min) were also increased relative to female controls (22.5 per min). With both treatments, significant covariances were revealed between vocalization rates and the left SDApc volumes [TP (rho), rho = .74: DES, rho = .43], but not the contralateral nucleus. Asymmetric development was absent in control females which received T as adults. Lateralization was specific to the SDApc, since no relationship was seen between either rates of calling and SCN volumes, or frequencies of nonvocal sexual components and the volumes of the SDApc or SCN. We conclude that steroid sex hormones influence lateralization of brain structure related to vocal behavior. The hormonal effect, which is likely to involve estrogen, occurs during neonatal development. PMID- 1742616 TI - Anorexia and adipsia: dissociation from fever after MIP-1 injection in ventromedial hypothalamus and preoptic area of rats. AB - Certain cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) act centrally to affect eating behavior and thermoregulation and may be involved in the physiological mechanisms leading to anorexia, adipsia and loss in body weight. The newly discovered macrophage inflammatory protein-1 (MIP-1) infused into the anterior hypothalamic, preoptic area (AH/POA) evokes an intense hyperthermia. The present experiments were designed to determine whether MIP-1 affects the feeding mechanism in the ventromedial hypothalamus (VMH) independently of the thermoregulatory mechanism in the AH/POA. For the microinjection of MIP-1, guide cannulae were implanted stereotaxically in the rat just above the VMH or AH/POA. Following postoperative recovery, each unrestrained rat was adapted to procedures whereby body temperature and intakes of food and water available ad lib were monitored at predetermined intervals. When an efficacious dose of 5.6 picograms (pg) MIP-1 was microinjected in a volume of 0.5 microliters into the VMH, the intake of food in the rat was reduced significantly in the short term and throughout the following 22 h. Within intervals of 30 min and 4.0 h following MIP-1, the amount of food consumed was 4.0 and 10 g, respectively, below that eaten by control rats given the saline solvent vehicle injected at the same site in the VMH. Over the entire test period, the intake of water was similarly significantly below that of the control rats. Whereas MIP-1 injected into the AH/POA evoked fever accompanied by a transient decline in feeding, the body temperature of the rats was unaffected by the cytokine injected in the VMH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742617 TI - Effects of haloperidol on motor and cognitive functioning in aged mice. AB - The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging induced changes in the behavioral effects of neuroleptic agents. PMID- 1742618 TI - Changes in physiological parameters of rat cerebrospinal fluid during chronic sampling: evaluation of two sampling methods. AB - Although rat cerebrospinal fluid (CSF) is increasingly being used in pharmacological and biochemical research, methodological studies on basic physiological data are lacking. We have determined the albumin content and number of erythrocytes and leukocytes in CSF obtained by two different methods of sampling from cisterna magna-repeated sampling from an implanted cannula and by repeated punctures. In the initial samples the albumin content was 0.08 +/- 0.03 micrograms/microliters. Chronic cannulation of the cisterna magna resulted in a meningeal reaction with increased cell and albumin content: a reaction that could be reduced but not prevented by using a sterile cannula. The number of leukocytes but not erythrocytes was highly correlated to the albumin content. Repeated sampling in the absence of a permanent cannula did not significantly increase albumin content but carried a higher risk for erythrocyte contamination. PMID- 1742619 TI - [Development of genetic and molecular approaches for the diagnosis and study of the pathogenicity of Helicobacter pylori, agent of gastric inflammatory diseases]. AB - Helicobacter pylori (H. pylori) is a small gram-negative bacillus, recently discovered, found in the stomach of patients with active chronic gastritis and duodenal ulcers. Production of a potent urease has been described as a trait common to all H. pylori so far isolated. To clarify the role of urease in the pathogenic process, as well as to engineer genetic tools useful for the diagnosis of H. pylori, we cloned the genes responsible for urease activity. A genomic library was constructed in Escherichia coli (E. coli) from the chromosomal DNA of the H. pylori strain 85P using a shuttle cosmind vector that we constructed in vitro capable of replicating both in E. coli and Campylobacter jejuni (C. jejuni). The genes responsible for the urease biosynthesis were cloned into E. coli host, then mobilized into C. jejuni where they were expressed. At least six different genes were shown to be required for the expression of the synthesis of an active enzyme; these genes belong to the same cluster and are regulated at the transcriptional level. The two genes encoding the two subunits of the urease enzyme were identified and sequenced; the products of these genes were compared to the other bacterial ureases. The genetic approach allowed to determine the amino-acid sequence of the most immunogenic antigens of H. pylori. In addition, it provides us with genetic tools: a 294-base pairs (bp) DNA fragment internal to one of the urease genes, was shown to be specific of H. pylori strains. This fragment was selectively amplified by polymerase chain reaction (P.C.R.) using two primers designed to target the urease region of all H. pylori isolates present in biological specimen. In addition, P.C.R. followed by direct DNA sequencing of the 294-bp amplified product was shown to be useful to identify and to distinguish between different H. pylori isolates. PMID- 1742620 TI - [Molecular and cellular bases of Shigella flexneri virulence]. AB - Shigella flexneri, a Gram negative bacillus, causes bacillary dysentery, an ulcerative disease of the human colon, by invading intestinal epithelial cells. Entry into epithelial cells occurs via an induced phagocytic process which involves the actino-myosin complex. The host-cell receptor and the transmembrane signal which initiate reorganization of the cytoskeleton are under study. Binding to integrins has recently been demonstrated in related models such as the entry of Yersinia pseudotuberculosis and Bordetella pertussis into cells. Bacterial genes necessary to achieve entry are located on five contiguous loci covering 30 kb on a 220 kb virulence plasmid in S. flexneri. Locus 2 has been particularly studied. Six genes organized as an operon encode highly immunogenic proteins among which IpaB (62 kD) and IpaC (48 kD) are the invasins of this microorganism which subsequently grows very rapidly within infected cells due to its capacity to lyse the membrane bound phagocytic vacuole. Once free within the cytoplasm, bacteria interact again with the cell cytoskeleton. They first express Olm (organelle like movement), a phenotype reflecting intracellular movement along actin stress cables. They subsequently express Ics (intracellular spread), a phenotype by which intracellular bacteria induce nucleation and polymerization of actin followed by accumulation of this material at one end of the bacillus. This process causes rapid random movement leading to the formation of protusions which allow passage to adjacent cells. A combination of these two movements achieves bacterial colonization of the epithelium. PMID- 1742621 TI - [Virulence factors of Salmonella: from molecular genetics to diagnostic applications]. AB - Salmonella serotype Typhimurium is a facultative intracellular pathogen that causes a systemic infection in naturally, or experimentally, infected mice. After oral contamination, Typhimurium colonizes the ileal mucosa and Peyer's patches and invades draining mesenteric lymph nodes. From these primary sites of infection, bacteria dissiminate to the reticuloendothelial system and proliferate rapidly in spleen and liver. Several virulence factors are encoded by chromosomal genes. The ability of Typhimurium to adhere to and invade epithelial cells has been associated with flagella, pili of type I and mannose-resistant haemagglutinating activity. By comparing the virulence of isogenic strains, it appeared that these traits played a marginal role and were not essential for full virulence expression. It is now clear that other surface structures are important for the invasiness capacity of Typhimurium. To multiply in the reticuloendothelial system, a complete lipopolysaccharide is necessary for the bacteria in resisting serum bactericidal activity and producing tissue damage. Salmonella have evolved a specialized iron-binding ligand, termed enterobactin, to acquire iron necessary for their multiplication. Enterobactin competes with the host iron-binding proteins (transferrin or lactoferrin) to secure the iron required by the bacteria. Though the presence of an enterotoxin in Salmonella is still controversial, there is now substantial evidence to support this concept. Recently, a gene encoding an enterotoxin has been cloned from Typhimurium and expressed in E. coli. Typhimurium strains harbour a 90 kilobases (kb) plasmid which is essential for virulence. This plasmid encodes virulence factors required for replication of Salmonella in liver and spleen. It was postulated that the plasmid allowed Typhimurium to multiply in Kupffer cells and in splenic macrophages. The virulence-associated region of the plasmid restored full virulence to plasmidless strains. Transposon insertion mutagenesis demonstrated the existence of two DNA sequences, designated Vir A and Vir B, which are essential for virulence expression. The Vir A region has been sequenced; it encodes four polypeptides with apparent molecular mass of 27,000, 28,000, 33,000 and 70,000. The Vir B region encodes two polypeptides of 38,000 and 43,000. In an attempt to identify bacterial components contributing to invasion of HeLa cells by Salmonella serovar Typhi, we cloned a 30 kb DNA sequence necessary for entry of bacteria into epithelial cells. However, this sequence is not sufficient for conferring an invasive phenotype to E. coli strains. From this DNA fragment, a short segment of 487 bp was subcloned, sequenced and used as probe to detect Salmonella.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742622 TI - [Multiple transplantation of abdominal organs]. AB - The transplantation of multiple abdominal viscera including liver-duodenum pancreas, liver-stomach-duodenum-pancreas, and liver-intestine is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multivisceral operation in which all of the foregoing organs are transplanted in bloc. It is described here how the full multivisceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation, and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component which is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment of the donor or of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact which then become the site of 2 way cell traffic after transplantation. Under powerful immunosuppression such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors of which insulin has been the most completely studied. An understanding of these various immunologic and non-immunologic factors combined with the more potent immunosuppression which is now available is sure to stimulate efforts at transplantation of abdominal organs and particularly of the hollow viscera which heretofore have resisted such clinical efforts. PMID- 1742623 TI - [Contribution of the incidence of urban sewage spreading to dietary chromium]. AB - The sewage sludges contain fertilizing matters that justify their use in agriculture. Simultaneously, they hold minerals that are directly proportional to the nature and intensity of industrial activity. The more abundant are chromium, lead, zinc; cadmium and mercury are also found. The concentration in chromium varies from 0.2 to 20.0 g/kg of dry matter. Its assimilation by the rootlet and, later, its intestinal absorption, are essentially dependent on its chemical state; the hexavalent forms have a high biodisponibility and are more toxic than the trivalent compounds. In vegetals, the assimilated chromium is stopped in the root, associated to iron hydrates; a small fraction reaches the leaves and a weaker part comes up to the grain. (Table I). If the concentration of chromium- mainly hexavalent salts--is very important in soil, the mechanism of regulation in the rootlet becomes inefficacious and chromium diffuses in the whole plant (Table II). The development of spraying of sludges and composts will increase the quantity and efficiency of chromium in vegetals, because of various factors: the wastes of many industries: chromium plating plants, tanneries, painting and dyeing industries throw out hexavalent chromium; if the sewage sludges are purified by an irradiation treatment, it will tend to oxidize the whole chromium in hexavalent forms; at last, the presence of sewage sludges in the arable soil favours the assimilation of chromium by inhibiting that of iron (Figure 1). Then, in absence of iron hydrates that regularize the diffusion of chromium in the plant, this latter tends to overrun more easily the aerial tissues and organs of vegetals. On the whole, the spraying of sewage sludges supplies the soil with chromium that will easily be assimilated by the plant, considering that it will be mainly at an hexavalent state. Compared with other trace elements held in the sludges, chromium is assimilated by the plant in a clearly more important proportion (Table III). That is why the consequences of spraying concern more particularly chromium than other elements, even if they are toxic. The intensification of spraying will contribute to increase the chromium intake that varies from 100 to 200 micrograms/day and whose 60% are provided by foods of vegetal origin. The consequences of a more important intake will be dependent on chemical state of chromium. If the hexavalent salts are predominant, an increase of intake will provoke a high intestinal absorption, a raising of chromium rate in liver, kidney, spleen, bone, etc. This situation will eventually be responsible for a chronic intoxication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742624 TI - [Clinical and biological epidemiology of onco-retroviral HTLV-I and II infections]. AB - Human T cell leukemia virus type I and II are endemic in South West Japan and in large parts of the equatorial belt in Central and South America, in Africa, and in some Pacific islands, areas where 1 to 5% of the general populations are infected. Pockets of high prevalence up to 15% and even 35% can be observed. The transmission of HTLV-I includes: maternal to offspring through breast feeding, sexual mainly from men to women and through blood exchange (blood transfusion, intravenous drug abusers, etc.) The diseases being proven to be caused by HTLV-I, include acute adult T cell leukemias as described in Japan, in 1977, in which the HTLV-I provirus is clonally integrated in leukemic cells, and a progressive spastic encephalomyelopathy named TSP/HAM, frequent in HTLV-I endemic areas, and in which an active viral replication takes place. No specific treatment being available, vaccine development, more feasible than for HIV, is critical since 8 to 12% of seropositive individuals develop HTLV-I associated diseases. PMID- 1742625 TI - [The draft decree to modify the decree n. 83-766 of August 24, 1983 standardizing the list of professional duties performed by speech therapists]. PMID- 1742626 TI - [Comparative physiology: saturated fatty acids and cholesterolemia in ruminants]. AB - Despite of great intestinal absorption of saturated fatty acids from rumen elaboration the cholesterolemia of ruminants is low. A such state comes from an important production of propionic acid in the rumen reducing hepatic cholesterol synthesis. PMID- 1742627 TI - [Importance of monoclonal antibodies in the analysis of tumor markers]. AB - Due to their extreme specificity, monoclonal antibodies (Mabs) have been very useful for new analytical progresses in the field of tumor markers. For example, it has been possible to analyse only calcitonin, independently of its precursors in the patients with medullary thyroid carcinomas. These precursors have been estimated and found increased in the absence of calcitonin for many cancer patients, specially with small cell lung tumors. The assay of HCG and its subunits with a great specificity and sensitivity is an other interesting example of the analytical power of Mabs. The usefulness of the assay of beta subunit is now clear in the diagnostic and follow up of choriocarcinoma and perhaps in the screening of high risk pregnancies. An other example can be derivated of our works on neuropeptide Y (NPY). The assay of NPY is highly difficult, due to its great similarity with other neuropeptides (PYY and PP). Mabs have been used to solve these analytical problems. The assay of NPY is useful not only for patients with neuroendocrine tumors, but also experimentally in the rat hypothalamus for research in nutrition. PMID- 1742628 TI - [Course of follicular lymphomas in a series of 281 patients]. AB - From 1963 to 1988, 281 patients suffering follicular lymphomas and without previous treatment were treated in the same institution. One hundred and thirty three had a localized disease (72 stages I, 61 stages II) ans 148 an extended disease (83 stages III and 85 stages IV). In the absence of dramatic therapeutic improvement quite all patients were treated in a homogeneous manner with radical radiotherapy for localized disease and palliative chemotherapy for extended ones. Median follow-up is 9 years. Ten year overall survival is 38% and relapse free survival 29.5%. Multivariate analysis show two main prognosis factors: age (+ or 60 years) and tumoral mass (as shown by stage or number of involved area). Survival depends also on complete remission. Age and tumoral mass allows us to define three prognosis groups: favorable, intermediate, unfavorable. These groups justify different therapeutic approach and different proposals for prospective therapeutic trials. PMID- 1742629 TI - [The African and Malagasy Council for higher education: objectives and programs]. AB - The African and Malgach Council for University Education is an inter-african institution. The anthors remind its organisation and show its aim and basic programms: recognition and equivalence of the degrees--teaching of the traditional medication--establishment of inter-african comettees--organisation of concors for associated professors in laws and medicine. PMID- 1742630 TI - [Peridural obstetrical analgesia and the cicatricial uterus. A 4-year evaluation]. AB - 191 women with previous cesarean section in 291 indexed between October 1985 and September 1989 underwent a trial of labor. 146 patients received epidural analgesia in the course of labor. Vaginal delivery occurred in 126 patients (86.3%). Duration for epidural analgesia in labour was 163 +/- 110 min. The intrauterine pressure for monitoring continuous was 51.00 +/- 15.40 mmHg. We report four uterine dehiscences and one rupture. In no case, epidural analgesia did not delay the diagnosis. The use of epidural analgesia for trial of labor in previous cesarean section did not increase maternal or fetal risk. PMID- 1742631 TI - [A phlebocavographic evaluation of the size of the inferior vena cava for the placement of a DIL percutaneous caval filter. A preliminary study apropos of 10 cases]. AB - With the DIL filter it is possible to make the partial interruption of the inferior vena cava percutaneously. It exists in three sizes corresponding to the variations of the size of the vena cava. The aim of this study is to estimate the real size of the vena cava by means of the radiological measures of the phlebocavography permitting--the correct choice of the size of the filter necessary for the optimisation of its efficiency--to avoid the difficulties of the placing. PMID- 1742632 TI - [Does the Leveen valve still have a place in the treatment of refractory ascites? An evaluation of 107 cases]. AB - One hundred and seven patients have been treated by the peritoneovenous shunt (PVS) : 54 patients from 1979 to 1984 (P1) and 53 patients from 1985 to 1990 (P2). The mean age was 58 years (25-79 years) and 73 % of the patients had a cirrhosis of alcoholic origin. The mortalities at two weeks and one month were 22 % and 26 % for P1 and 6 % and 11 % for P2. The risk of operation was related to the importance of hepatic and kidney insufficiency and to the importance of hyponatremia. Long term outcome depended on the causal illness. At short term, the morbidity can be reduced and the PVS should be indicated earlier in the progression of the illness. PMID- 1742633 TI - [Postoperative analgesia in shoulder surgery using an interscalene catheter: 3 years' experience]. PMID- 1742634 TI - [Postoperative analgesia using propacetamol]. AB - Postoperative analgesia using propacetamol was studied in 50 patients, 42 +/- 16 years old, after little or moderate surgery. Two grams of propacetamol in intravenous perfusion were administered every six hours. Three scales were utilized to note the intensity of the pain (simple verbal, behavioral and visual analogue scales), before the first injection and, one, four, six hours after. From this study, satisfactory analgesic efficiency and good tolerance of propacetamol were established. PMID- 1742635 TI - [Collective medical transport by air of the war wounded]. PMID- 1742636 TI - [Inverted vision following transurethral resection of the prostate]. PMID- 1742637 TI - [Prolonged curarization in a case of Lambert-Eaton syndrome]. PMID- 1742638 TI - [Acute paranoia following a sudden alprazolam withdrawal]. PMID- 1742639 TI - [Characteristics and limitations of pediatric anesthesia in a non-university milieu (private hospital)]. PMID- 1742640 TI - [A comparative study of 3 preventive anticoagulation protocols used successively in orthopedics at the CHU of Limoges. A retrospective study of 953 total hip prostheses (single or repeat)]. PMID- 1742641 TI - [Resuscitation following poisoning and asphyxia. 1877]. PMID- 1742642 TI - Bronchial hyper-reactivity and skin sensitivity. PMID- 1742643 TI - Topical capsaicin therapy in chronic rhinitis: a way forward? PMID- 1742644 TI - Investigative use of bronchoscopy, lavage and bronchial biopsies in asthma and other airways diseases. PMID- 1742645 TI - Methotrexate in asthma. PMID- 1742646 TI - Fibroblasts and asthma. PMID- 1742647 TI - Radioimmunoassay of human eosinophil cationic protein (ECP) by an improved method. Establishment of normal levels in serum and turnover in vivo. AB - A radioimmunoassay was developed allowing measurement of the cytotoxic cationic ECP. The assay, which has a total incubation time of 3.5 hr, is a double antibody assay with radiolabelled ECP, covering the concentration range of 2-200 micrograms/l. Performance data show a detection limit of less than 2 micrograms/l and a cross-reactivity with eosinophil protein X (EPX/EDN) of less than 0.06%. The coefficient of variation (%) within the measuring range was, within assay 4.8 10.4, and total 6.6-12.0. The assay is useful for measurement in various body fluids including serum, nasal secretions and bronchoalveolar lavage fluid, and dilution of samples prior to analysis was generally not required. Sera from 100 apparently healthy individuals revealed a geometric mean of 6.0 micrograms ECP/l and a range (95%) of 2.3-15.9 micrograms/l. The elimination rate of ECP, t1/2, in vivo was estimated to be 65 min when ECP was measured in serum. Comparisons between this assay and a method previously described showed that the new method is superior with regard to precision and assay procedure. PMID- 1742648 TI - Double-blind cross-over trial of oral sodium cromoglycate in patients with irritable bowel syndrome due to food intolerance. AB - Twenty patients with irritable bowel syndrome due to food intolerance were randomized to either oral sodium cromoglycate or placebo in a double-blind cross over trial. The study consisted of treatment with either sodium cromoglycate or placebo for 8 weeks, followed by the cross-over treatment for 8 further weeks. Patients were allowed to eat the offending foods during the study. Eighteen patients completed the study. Analysis of patients' diary card scores showed a statistically significant difference in favour of sodium cromoglycate. There was a long carry-over effect in the active-placebo order group. Therefore oral sodium cromoglycate seems to be a useful treatment in patients with irritable bowel syndrome and proven food intolerance. PMID- 1742649 TI - Sensitivity to common allergens: relation to respiratory symptoms and bronchial hyper-responsiveness in children from three different climatic areas of Australia. AB - In order to examine further the relation between atopy, as defined by skin-prick tests, and respiratory illness, we studied three populations of schoolchildren aged 8-11 years and living in different climatic areas of New South Wales, Australia. Skin-prick tests were performed using 13 commercial allergen extracts. Respiratory and allergic symptoms were assessed using a self-administered questionnaire to parents and bronchial hyper-responsiveness (BHR) was measured by histamine inhalation test. We defined current asthma as BHR together with symptoms of wheeze in the 12 months prior to study. Children with one or more positive skin weals of greater than or equal to 3 mm had significantly more recent wheeze, hayfever, eczema and BHR than children with smaller weals (P less than 0.001). In each area, 95-97% of all atopic children were sensitized to one of the following seven allergens: house dust, Dermatophagoides farinae, D. pteronyssinus, cat dander, plantain, rye grass, and Alternaria tenuis. Thus, these seven selected allergen extracts and a skin weal of 3 mm could be used to detect clinically relevant atopy in these populations of children. Sensitivity to house dust mite had the strongest independent association with current asthma in all three areas. The associations of other allergen sensitivities with BHR or current asthma were area dependent, indicating the influence of local allergen levels on respiratory illness in children. The potency of house dust mite sensitivity in increasing the risk of children having BHR and current asthma is confirmed. PMID- 1742650 TI - Unilaterality of obstruction after acute nasal allergen provocation. Relation of allergen dose, nasal reactivity and the nasal cycle. AB - We examined unilaterality of obstruction after acute bilateral nasal allergen provocation in two groups of pollen-sensitive volunteers studied out of season. One group was challenged on one occasion with a threshold allergen dose and on another with placebo. We measured nasal airway resistance (NAR) unilaterally for 3.5 hr before the challenges and for 40 min after. Most subjects' noses had marked asymmetry of response. Over half showed marked obstruction on one side and none at all on the other side. The side which showed higher resistance and greater lability before challenge was typically more obstructed after. In a second group we compared responses to threshold and x 10 threshold doses. Threshold challenge produced results similar to those seen with the first group. After the higher allergen dose, there was some obstruction in the less responsive side and the rate of rise was much slower. Obstructive response after acute threshold allergen challenge is typically one-sided. This pattern may be related to the stage of the nasal cycle in which the challenge was delivered. Higher allergen doses produce more obstruction in the less responsive side but the response is still asymmetrical. PMID- 1742651 TI - Skin prick testing using allergen-coated lancets: a comparison between a multiple lancet device and a single lancet applied with varying pressures. AB - Allergen-coated lancets have been developed to simplify skin prick testing. The effect of variation in application pressure on the response to prick tests was assessed in 20 atopic subjects, and the results compared to the response obtained with a newly devised multiple lancet device (MLD), capable of holding up to eight lancets and of providing a standardized application pressure. A positive weal (greater than or equal to 7 mm2) using light pressure occurred in 2/20 subjects, compared with 14/20 after moderate pressure. The largest weals were obtained using hard pressure and with the MLD (all 20 subjects obtained positive weals) and there was no significant difference in weal size between the two. There was evidence of a late reaction in 4/17 subjects with the MLD and with hard pressure applied to a single lancet, but in only one with moderate and in none with light pressure. Thus both the early and late skin responses are dependent on the pressure applied. The newly designed MLD allows skin prick tests to be performed using a standard pressure. It is also convenient for multiple allergen testing of uncooperative children. PMID- 1742652 TI - Improvement of symptoms of non-allergic chronic rhinitis by local treatment with capsaicin. AB - Sixteen adult patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse for more than a year, received, under local anaesthesia, an intranasal spray of capsaicin (3.3 x 10(-3) mol), the pungent agent in hot pepper, once weekly for 5 weeks. The subjective intensity of their nasal obstruction, rhinorrhoea and sneezing frequency were evaluated throughout the study and the vascular effects of capsaicin on the nasal mucosa were recorded by anterior rhinomanometry and laser Doppler flowmetry. Calcitonin gene-related peptide (CGRP) is a vasodilator agent present in sensory nerves and may play a major role in the vascular component of neurogenic inflammation. Therefore, the nasal mucosa content of CGRP-like immunoreactivity (CGRP-LI) was determined by radioimmunoassay in biopsies obtained before and after the capsaicin treatment. Intra-nasal capsaicin application evoked a larger vascular response in patients with rhinitis than in controls (P less than 0.05). Both nasal vascular responses and subjective discomfort following capsaicin were markedly reduced after the fifth application (P less than 0.01). In parallel, a 50% reduction of the CGRP-LI content in the nasal biopsies was observed. All symptoms were significantly improved throughout a 6 month follow-up period. No significant side-effects occurred and weaning from nasal vasoconstrictor agents was possible. Both the subjective symptom score and objective measurements of vascular reactivity suggest that repeated intra-nasal capsaicin application could be beneficial for patients with chronic rhinitis, possibly by reducing hyperreactive nasal reflexes. PMID- 1742653 TI - Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease. AB - Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved. PMID- 1742654 TI - Allergy from cellulase and xylanase enzymes. AB - Modern biotechnical methods have enabled production of many new types of potentially allergenic proteins. Enzymes have long been known to be respiratory allergens, but relatively few cases of skin allergy have been reported. Here we describe four patients who developed occupational allergic respiratory symptoms, three with bronchial asthma and one with allergic rhinitis, caused by cellulase and/or xylanase enzymes. Each patient also had urticarial symptoms after skin contact with these enzymes. In addition, one of the patients had allergic contact dermatitis from cellulase, and one from xylanase. Allergic contact dermatitis was verified by positive patch tests with the enzymes, and the immediate allergy was revealed by skin prick tests, specific IgE determinations (RAST) and RAST inhibition tests. All patients had positive RASTs to both cellulase and xylanase. In the RAST inhibition test 20 microliters of cellulase brought about a 94% inhibition, indicating the specificity of the RAST. Xylanase (20 microliters, 5% w/v) gave an 92% inhibition of cellulase RAST, indicating cross-reactivity between cellulase and xylanase. Three patients have been able to continue at their previous places of work, but at different worksites. One of the patients requires continuous medication for asthma and had to change her job because of persistent symptoms. PMID- 1742655 TI - A case of occupational asthma, rhinitis and urticaria due to sesame seed. PMID- 1742656 TI - Psychological treatments of asthma. PMID- 1742657 TI - Consumer report says "Amalgam fillings are still best bet". PMID- 1742658 TI - "The silver-mercury connection"--a report. PMID- 1742659 TI - Biocompatibility. PMID- 1742660 TI - Esthetic resin posterior restorations. PMID- 1742661 TI - Computer systems for dental practice management. A new generation of independent dental software. AB - A new generation of computer programs for dental patient management eliminates total dependence on the vendor for programming support. The software design enables information collected with the dental system to be transferred to popular off-the-shelf programs designed for business. A simplified example is used to illustrate for practitioners the advantages of this type of data structure management. Programs designed on this basis offer optimum performance and expandibility for both present and future needs. PMID- 1742662 TI - Orthodontic treatment for the adult periodontal patient. AB - The purpose of this article is to outline a method of orthodontic treatment for adult patients, particularly those with periodontal disease. The rationale for recommending orthodontics to these patients is discussed, with an emphasis on periodontal and occlusal management during treatment. Methods of using orthodontics to improve the periodontal status of adult patients are also demonstrated. Finally, there is a brief discussion on retention, and age considerations, as well as the obligations of both dentists and patients. PMID- 1742663 TI - Effects of glove powder on radiographic quality. AB - The use of powered rubber gloves in the provision of dental care has produced a new variable in radiographic quality assurance procedures. Wearing powder-coated gloves while processing X-ray films can reduce the quality of the images obtained on processed radiographic film. To ensure that the optimum quality of processed film images is achieved, the operator must be careful to prevent the contamination of the film and processing solutions with powder. PMID- 1742664 TI - A clinical study of radiographic selection criteria for edentulous patients. AB - This study was designed to determine if radiographic selection criteria could be developed and applied in the examination and treatment planning of edentulous patients. Fifty-one patients were examined and radiographs were prescribed for seven patients, where indicated by the selection criteria chosen. Previously obtained screening panoramic films were interpreted first, for findings in the areas covered by the prescribed films, and then for occult findings in the remaining areas. Thirty-three patients showed occult positive findings, none of which had clinical significance. For this population, the prescription of radiographs provided the appropriate radiographic information for making treatment decisions. For the vast majority of patients (49), screening panoramic films were unproductive and therefore unnecessary. PMID- 1742665 TI - Benign mucous membrane pemphigoid: a case report. AB - A relatively rare systemic disease, benign mucous membrane pemphigoid (cicatricial pemphigoid) usually starts in the mouth and is clinically characterized by bullae that rupture and form an ulcer. A distinctive Nikolsky's sign is apparent using gentle air blasts or finger pressure. The pharynx, larynx, nose, esophagus, genitals and eyes can also be affected. Involvement of the conjunctivae can lead to scarring and ensuing blindness. The following case of a healthy 77-year-old man, diagnosed as suffering from mucous membrane pemphigoid, is of particular interest since several confusing clinical observations, including poor oral hygiene, the possibility of a contact dermatitis or an adverse antibiotic reaction, made the diagnosis more difficult. A careful medical history, examination and consultation process is paramount to initiating proper treatment and subsequent relief of symptoms. Benign mucous membrane pemphigoid must always be considered in any patient with desquamative epithelium of the oral mucosa. PMID- 1742666 TI - High density lipoproteins and coronary artery disease. PMID- 1742667 TI - Human clinical trials of the dilatable pulmonary artery banding prosthesis. AB - OBJECTIVE: To test the hypothesis that the dilatable pulmonary artery banding prosthesis is as effective and safe to use as conventional fixed fabric bands, and provides an additional nonsurgical option for dilation. DESIGN: Nonrandomized prospective human clinical trial. SETTING: British Columbia's Children's Hospital for tertiary care. PATIENTS: All patients admitted with congenital heart defects who required banding of the pulmonary artery during a 17 month period. The patients who received a dilatable band were selected on the basis of their cardiologist's preference. INTERVENTIONS: Surgical banding was performed using accepted techniques. Intraluminal balloon dilation of the pulmonary artery band was done using techniques accepted for intraluminal balloon dilation in pulmonary valvuloplasty. MAIN RESULTS: Eleven patients received the dilatable bands and eight received fixed bands. There was no evidence of failure of the bands to maintain their function. One patient required intraluminal balloon dilation of the dilatable band. This was successfully accomplished without complication. The dilatable bands were easier to remove than the fixed bands, but required greater surgical dexterity to place and adjust. One of the dilatable bands was applied too distally and one too tightly. One fixed band was applied too tightly and another too loosely, requiring a second banding operation. CONCLUSIONS: The dilatable pulmonary artery banding prosthesis is as effective and safe to use as a fixed fabric band. It is easier to remove and provides a nonsurgical option for dilation. PMID- 1742668 TI - Cardiac abnormalities in patients with systemic lupus erythematosus. AB - OBJECTIVE: To determine the prevalence of cardiac abnormalities in patients with systemic lupus erythematosus. DESIGN: Prospective survey. SETTING: Rheumatic diseases unit of a university hospital. PATIENTS: Volunteer sample comprising 83% of patients with systemic lupus erythematosus followed annually in the rheumatic disease unit (93 patients; mean age 46 +/- 13 years; female 79, male 14). These patients were age-matched with 16 female control volunteers (mean age 43 +/- 5 years) recruited from hospital staff. INTERVENTIONS: Electrocardiograms, two dimensional echocardiograms and radionuclide angiograms were performed in patients and controls. Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay in the systemic lupus erythematosus patients. MAIN RESULTS: At least one cardiac abnormality was detected in 44 of 93 systemic lupus erythematosus patients (47%). These abnormalities included: aortic valve thickening 12%; mitral valve thickening, prolapse, vegetations or stenosis 23%; left ventricular segmental dysfunction 4%; left ventricular global hypokinesis 4%; right ventricular hypokinesis 4%; left ventricular hypertrophy 14%; left ventricular diastolic dysfunction 16%; and pericardial effusion 2%. Three of the 16 controls (19%) had cardiac abnormalities consisting of mitral valve prolapse (one), right ventricular hypokinesis (one) and pericardial effusion (one). Cardiac abnormalities were more common in the systemic lupus erythematosus group compared with controls (47% versus 19%, P less than 0.05). Raised anticardiolipin antibodies were specific (88%) but not sensitive (33%) for the presence of cardiac abnormalities in systemic lupus erythematosus patients. Renal disease and prednisone therapy were more common in systemic lupus erythematosus patients with cardiac involvement than in such patients without evidence of cardiac disease (40% versus 16%, P = 0.03; and 81% versus 59%, P = 0.04, respectively). CONCLUSIONS: Cardiac abnormalities can be identified noninvasively in 47% of patients with systemic lupus erythematosus. PMID- 1742669 TI - Normalized left ventricular filling indexes to detect diastolic dysfunction in hypertension and in hypertrophic cardiomyopathy. AB - In order to establish a normalizing method for left ventricular filling indexes, peak filling rate (PFR) and time to peak filling rate (TPFR), derived from resting radionuclide ventriculography using Fourier analysis with third-order harmonics, were analyzed in 45 normal subjects, 40 hypertensive patients, and 29 patients with hypertrophic cardiomyopathy. PFR was significantly negatively correlated with age (r = -0.62) and significantly positively correlated with peak ejection rate (PER) (r = 0.58) in normals. TPFR normalized for heart rate (N TPFR) was correlated positively with age in normals (r = 0.60) and hypertensives (r = 0.49) but not in patients with hypertrophic cardiomyopathy. N-TPFR was not significantly correlated with systolic parameters. A significant relationship between PFR normalized to PER (PFR/PER) and age was observed in normals (r = 0.58) but not in patients with hypertension or hypertrophic cardiomyopathy. To cancel the ageing effect, individual data of PFR/PER and N-TPFR were expressed as a percentage of the predicted regression value in normal subjects (%PFR/PER and %N-TPFR, respectively). Per cent PFR/PER was significantly lower and %N-TPFR was significantly greater in patients with hypertension and hypertrophic cardiomyopathy compared to normals. When normal limits of these indexes were defined as %PFR/PER greater than 80% and %N-TPFR less than 120%, the sensitivity, specificity and diagnostic accuracy of differentiating normals from patients with hypertension or hypertrophic cardiomyopathy were 41 of 45 (91%), 44 of 68 (65%), and 85 of 113 (75%), respectively. These findings indicate that %PFR/PER and %N TPFR might be more reasonably normalized parameters for describing diastolic filling and its abnormality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742670 TI - The effectiveness of various modes of nonsynchronized retrovenous perfusion in salvage of ischemic myocardium in the pig. AB - The effectiveness of intermittent coronary sinus occlusion was compared to a new non-electrocardiogram-synchronized coronary sinus retroperfusion system in terms of ability to reduce myocardial infarct size. In 40 anesthetized, open-chest pigs the left anterior descending coronary artery was occluded for 4 h and then reperfused for 1 h. In the arterial group, the coronary sinus was intermittently occluded (5 s inflation, 5 s deflation) with retroperfusion of arterial blood at 60 mL/min during balloon inflation. In the venous group, the protocol was identical to the arterial group except that venous blood was retroperfused at the same flow rate during balloon inflation. In the intermittent coronary sinus occlusion group, the coronary sinus was similarly occluded, but there was no active retroperfusion. In the control group, no intervention was performed. In the three experimental groups, retroperfusion was maintained throughout the 4 h occlusion period. Infarct size, assessed by tetrazolium staining and expressed as a percentage of the in vivo area at risk, was greater in control animals (86.3 +/ 7.5%) compared to either arterial (44.1 +/- 12.9%; P less than 0.001) or venous groups (57.7 +/- 15.5%; P less than 0.001) but not compared to the intermittent coronary sinus occlusion group (78.0 +/- 10.2%; not significant). Active retroperfusion with arterial blood did not achieve significantly greater salvage compared to active retroperfusion with venous blood (not significant), although both produced significantly greater salvage than intermittent coronary sinus occlusion (P less than 0.03). Mean coronary sinus pressure was 56.1 +/- 25.4, 38.8 +/- 5.6 and 17.1 +/- 6.4 mmHg in the arterial, venous and intermittent coronary sinus occlusion groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742671 TI - The Canadian Atherosclerosis Society--history and present status. AB - Since its inception in 1983 the Canadian Atherosclerosis Society (CAS) has established itself firmly on the national and international scene as a forceful scientific voice. Its presence and activities have had their dominant expression at annual meetings held jointly with the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Canadian Society for Clinical Investigation (CSCI) and in sponsoring other scientific and educational events, the most important of which was the Canadian Consensus Conference on Cholesterol (Ottawa, March 1988). It provided a forum for interaction between the scientific community, government, funding agencies, industry and the general public, and culminated in concrete recommendations for the populace of Canada. It also 'induced' a continuum in governmental and public concern for health with respect to atherosclerosis, and beyond it, the field of cardiovascular diseases. This dialogue continues. As a member (Constituent Society) of the International Atherosclerosis Society (IAS), the CAS has a voice in the international community, its policies and activities. The membership increase from 69 in 1983 to 175 in 1991 reflects steady growth of the CAS. The Society has been active in other areas (publications, awards for young investigators, and common educational endeavours with other groups) and will be host to the 1994 International Symposium on Atherosclerosis. Over a short period of only eight years, all of the above attests to sufficient progress (or achievement) for any scientific society. And yet, there remain quite a few areas not addressed as yet and some sad experiences (eg, that with the Long Term Planning Committee) that must be quickly remedied, if the Society is to keep pace with the everchanging emphasis in research that in the final analysis aims at improving the overall well-being and health of all Canadians. Inherent in the definition of history is the premise that accounts be provided of facts only. Historians who research their subjects derive these facts from studying the necessary accounts relating to these 'facts', using different and preferably controversial resources, so as to present the facts as objectively as possible. It is impossible, however, to fulfill all the above criteria for a historian who lived through every phase of 'life' of the subject of his or her account, because no matter how objective one wishes to remain (and bends backwards to achieve this) there will be always an element of a personal prism through which the historian lived the 'life' with his subject. For being human and thus unable to eliminate entirely that personal component, this writer asks humbly for the reader's understanding. PMID- 1742672 TI - Pictorial essay: transabdominal and endovaginal sonography of adnexal masses. AB - Endovaginal sonography is rapidly becoming the diagnostic procedure of choice when evaluating patients with early pregnancy and assessing uterine abnormalities. However, there has been relatively little discussion of endovaginal sonography in the evaluation of adnexal masses. Using endovaginal sonography we studied 50 patients with clinically suspected adnexal masses, in whom transabdominal sonography was either suboptimal or failed to adequately characterize the mass. The purpose of this pictorial essay is to depict the normal anatomy of the ovaries and adnexa and highlight the unique contribution of endovaginal sonography in diagnosing a variety of adnexal masses, including tubal and ovarian lesions. PMID- 1742673 TI - Screening for breast cancer with mammography. AB - Mammography is generally accepted as a useful problem-solving clinical tool in characterizing known breast lesions, so that appropriate and timely treatment can be given. However, it remains grossly underutilized at what it does best: screening. The major strengths of mammography are a) its ability to detect breast cancer at a smaller, potentially more curable stage than any other examination, and b) its proved efficacy in reducing breast cancer mortality in asymptomatic women aged 40-74. If, as has recently been estimated, screening with mammography and physical examination can be expected to lower breast cancer deaths by 40%-50% among those actually examined (13), then the lives of almost 20,000 U.S. women might be saved each year if screening were to become very widely used. The challenges of the next decade are clear, to mount much more effective campaigns to educate physicians and lay women about the life-saving benefits of breast cancer screening, to devise increasingly effective and lower cost screening strategies, to further improve the current high quality of mammographic imaging despite its increasing proliferation, and to train large numbers of breast imaging specialists to guarantee that the growing case load of screening and problem-solving mammograms is interpreted with a very high level of skill. PMID- 1742674 TI - Infected abdominal aortic aneurysm due to Salmonella: CT evaluation. AB - Two cases of infected abdominal aortic aneurysm (IAAA) caused by salmonella are reported and the computed tomography (CT) features are discussed and compared with the pathologic findings. Additionally, a review of the literature was performed. A well-enhanced para-aortic mass (PAM) beyond the calcified intima of the abdominal aorta on the CT, which was initially considered to represent a leakage from the infected aneurysm, was observed in 5 of the 6 reported cases (including ours) and identified as a pseudoaneurysm. In one case, multiple gas collections within the PAM were demonstrated for the first time in IAAA due to salmonella. PMID- 1742675 TI - Mesenteric panniculitis: findings on CT, MRI, and angiography. Case report. AB - The computed tomography (CT), magnetic resonance (MR), and angiographic features of a case of mesenteric panniculitis are presented. The MR characteristics of this rare disorder have not previously been reported. The value of MR in arriving at the preoperative diagnosis of this disorder is discussed. PMID- 1742676 TI - Detection of internal mammary lymph node enlargement: comparison of CT scans and conventional roentgenograms. AB - Sixty-two patients with breast cancer had thoracic computed tomography (CT) scans and conventional chest radiographic (CXR) examinations separated by an average of 29 days. CT served as the gold standard showing 13 cases with enlarged internal mammary nodes 0.4 to 7 cm in diameter. Original CXR interpretations were available. Additionally, these films were reinterpreted, without knowledge of the CT results, with special attention to the retrosternal region on the lateral film including the use of a bright light and comparison to prior lateral views. Original CXR interpretations detected only one (7 cm) enlarged node. Sensitivity was 8% and specificity 100%. Reinterpretation of the CXRs, without knowledge of the CT results, with special attention to the retrosternal region yielded five true positive and seven false positive determinations for a sensitivity of 38% and specificity of 86%. No enlarged node under 2.5 cm in diameter was detected on CXR. Sensitivity of CXR can be considerably improved by careful evaluation of the retrosternal space, but at the cost of considerable increase in false positive examinations. CT is necessary to achieve reasonable sensitivity and specificity in the detection of internal mammary lymphadenopathy. PMID- 1742677 TI - Venous sinus thrombosis as a cause of parenchymal and intraventricular hemorrhage in the full-term neonate. AB - A case of parenchymal and intraventricular hemorrhage in a full-term neonate is reported. The underlying cause in our patient is thought to be related to cerebral sinovenous occlusive disease secondary to Protein C deficiency, a rare coagulopathy. PMID- 1742678 TI - Imaging of retroperitoneal rhabdomyosarcoma mimicking hypernephroma. AB - Malignant tumors that arise in the perinephric space often present a diagnostic dilemma. These retroperitoneal tumors may resemble renal carcinomas, extrahepatic lymphoma, metastatic disease, or tumors arising in other retroperitoneal organs. We present a case of a patient with a primary retroperitoneal rhabdomyosarcoma who had an extensive diagnostic workup prior to surgical intervention that was thought to be consistent with an aggressive renal cell carcinoma. PMID- 1742679 TI - Communicating intrathoracic hydrocele. AB - Tense ascites may cause herniation of parietal peritoneal reflection into the mediastinum at the gastroesophageal junction. This may produce a mass visible on chest radiograph and computed tomography (CT). This communicating intrathoracic hydrocele may occur in the absence of hiatal hernia and may be confused with other middle mediastinal fluid collections including necrotic tumor, abscess, cyst of foregut origin, or pancreatic pseudocyst. Recognition of this entity in patients with ascites should prevent diagnostic confusion and unnecessary further evaluation. PMID- 1742680 TI - Osseous metastasis in medulloblastoma: MRI findings in an unusual case. AB - An 11-year-old boy with a history of medulloblastoma developed blastic osseous metastases. The metastases were detected by noting diffuse areas of low signal intensity within the calvarium on T1-weighted and T2-weighted magnetic resonance (MR) scans of the brain. The MR appearance of osseous metastases in medulloblastoma has not been reported previously. Extraneural metastases in medulloblastoma are relatively rare. The literature is briefly reviewed. PMID- 1742681 TI - Ossifying fibroma in the nasopharynx. A case report. AB - Ossifying fibroma localized in the nasopharynx of a 35-year-old man with histopathologic and radiologic findings has been reported. Because of its rarity, the subject has been presented and discussed. PMID- 1742682 TI - Metastatic hypernephroma masquerading as acute cholecystitis. AB - Renal cell carcinoma can metastasize to multiple anatomic sites. The metastasis may simulate certain disease entities depending on the location and particular organ involved. It is important to recognize that these metastases can present many years after the primary tumor has been treated. We present a case in which a primary hypernephroma was surgically removed and subsequently 13 years later presented with metastatic disease to the gallbladder clinically simulating acute cholecystitis. PMID- 1742683 TI - Detection of the fetus in the cul-de-sac by transabdominal and transvaginal ultrasound. A case report. AB - The most common reason for a fetus in the cul-de-sac is ectopic pregnancy, such as rupture of tubal pregnancy, ovarian pregnancy, and intraabdominal pregnancy (1 3). A case of the fetus in the cul-de-sac complicated by uterine perforation was imaged transabdominally and transvaginally on September 13, 1990. PMID- 1742684 TI - Perinephric hemorrhage secondary to adrenal myelolipoma. Case report. AB - Spontaneous perinephric hemorrhage has been described as occurring secondary to a number of primary renal abnormalities, but rarely from other causes. We describe the computed tomography (CT) and ultrasound findings of this event resulting from hemorrhage from an adrenal myelolipoma. PMID- 1742685 TI - Health care in Ontario. PMID- 1742686 TI - Drinking and pregnancy. PMID- 1742687 TI - CPPNW turns pacifist. PMID- 1742688 TI - Guidelines for medical technology in critical care. PMID- 1742689 TI - Meeting the iron needs of infants and young children: an update. PMID- 1742690 TI - Jehovah's Witnesses and the transfusion debate: "We are not asking for the right to die". PMID- 1742691 TI - Hazard of yawning. PMID- 1742692 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1742693 TI - Ontario's health number: a threat to privacy and a solution. PMID- 1742694 TI - Non-insulin-dependent (type II) diabetes mellitus. AB - Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that will enhance effective insulin secretion and action and inhibit the progress of complications. PMID- 1742695 TI - Increasing brain cancer rates in Canada. AB - OBJECTIVE: To analyse brain cancer patterns in Canada, particularly according to age and sex distributions, temporal patterns and regional variations. Changes in diagnostic techniques, survival rates and trends by tumour type were also examined. DESIGN: Descriptive epidemiologic study based on Canada-wide population data for 1959-88. OUTCOME MEASURES: Rates of death, incidence and admission to hospital because of brain cancer, as well as survival time and methods of diagnosis. SUBJECTS: Incidence and death rates and time trends were examined for Canada as a whole, by province and by census division. RESULTS: The rates of death from brain cancer increased rapidly among Canadians aged 55 years or more from 1959 to 1988. In particular, age-adjusted death rates increased by 117%, 797% and 118% among men 65 to 74 years, 75 to 84 and 85 or more respectively. The corresponding increases among women were 138%, 535% and 400%. The incidence rates also increased substantially. The trends in incidence rates by tumour type indicated that the increase was more pronounced for glioblastomas. The incidence rates of cases detected histologically, radiologically and clinically all increased. CONCLUSIONS: Because glioblastomas are generally easier to diagnose than astrocytomas and because the incidence rates of glioblastomas were found to increase substantially, the increased brain cancer rates among elderly people may not be entirely attributable to improved diagnostic techniques. However, analytic investigations of the impact of changes in diagnostic procedures on brain cancer trends are needed to clarify this issue. PMID- 1742696 TI - Five cases of erroneously diagnosed HIV infection. PMID- 1742697 TI - Hyperlipidemia in pregnancy. PMID- 1742698 TI - The menace of obesity. 1926. PMID- 1742699 TI - It is time for a new consensus on animal-based experimentation. PMID- 1742700 TI - It is "almost easier" to find human research subjects than animal ones, researcher says. PMID- 1742701 TI - Fat's in the fire in British food fight. PMID- 1742702 TI - Canada's medical manpower problems pale in comparison with Germany's. PMID- 1742703 TI - Lesbians face unique health care problems. PMID- 1742704 TI - Breast implants do not appear to pose cancer risk, Alberta researcher says. PMID- 1742705 TI - Dr. Wilfred Grenfell and the forgotten people of Newfoundland and Labrador. PMID- 1742706 TI - A multidisciplinary treatment approach to postpartum psychoses. AB - Psychosis after childbirth occurs as a result of unique developmental and social demands. The authors have developed a treatment approach for the management of postpartum psychotic mothers admitted with their babies, based on their experience on an acute psychiatric inpatient unit with a special interest in the treatment of postpartum disorders. Five phases of the acute illness and recovery process are outlined. For each phase, a typical clinical situation, the specific tasks of the phase, and special problem areas are presented. The management guidelines are based on a multidisciplinary team and phase-oriented approach. PMID- 1742707 TI - Dimensions of personality pathology. AB - The reliability of DSM-III-R diagnoses of personality disorders is poor and their validity has yet to be established. There is little evidence that the features of personality pathology cluster into these diagnostic entities. For these reasons, it is important to explore alternative ways of classifying personality disorders. In this preliminary study, reliable scales were developed to assess 100 personality dimensions which were systematically developed. The factorial structure underlying the dimensions was evaluated in a heterogeneous sample of 110 subjects from the general population. Sixteen components, accounting for 81.4% of the variance, were retained for rotation to oblique structure. The components were labelled social avoidance, narcissism, insecure attachment, compulsive behaviours, interpersonal disesteem, mobility, anxiousness, conduct problems, stimulus seeking, identity disturbance, self-harm, rejection, diffidence, and hypersensitivity. Two components were not interpreted because they only had one or two salient loadings. PMID- 1742708 TI - Psychiatric aspects of heart transplantation. AB - Psychiatrists have been an integral part of the heart transplant team at the Royal Victoria Hospital in Montreal since the program was set up in September 1984. One hundred and twenty five candidates were evaluated for the operation; 12 were found to be unsuitable for surgery because of psychiatric illness. Heart transplant recipients who had previously suffered from a psychiatric disorder fared worse than those who had not. The psychiatrist's recommendations for or against surgery depended on the patient's ability to cope with a number of stressors, including compliance with the medical regimen, waiting for a donor, the surgical procedure itself, adaptation to life with a new organ, and the resolution of a distressing emotional state. Post-operative complications ranged from organic mental syndromes to depression. With the increase in heart transplantations, the competition for organ donors is intensifying and patient selection requires greater involvement of psychiatrists. PMID- 1742709 TI - Psychiatric disorders in children and adolescents: the contribution of the child's temperament and the parents' psychopathology and attitudes. AB - Correlates of child psychopathology were studied in a community sample of 210 children and adolescents (with equal numbers of boys and girls). Children suffering from a psychiatric disorder had more temperamental difficulties and their parents showed a higher level of psychopathology than those without a disorder. Furthermore, a regression analysis revealed that difficult temperamental traits in the child and the parents' attitudes toward the child were primary predictors of psychiatric disorders in the child. The relationship between the parent and child as well as the environment-temperament impact on child psychopathology are discussed. PMID- 1742710 TI - Evaluation of I-C papaverine in patients with psychogenic and organic impotence. AB - Forty men with organic or psychogenic impotence, who were highly motivated for treatment, were offered instruction in the intracavernosal (I-C) self-injection of papaverine and regular ongoing supervision by the investigator. Twenty declined immediately, citing a number of reasons, notably qualms about pain of the injection, side-effects and the unnaturalness of the method. Eleven patients discontinued the drug within 11 months; nine used it for at least one year, and all were continuing with it albeit less frequently at the time of assessment. Those who discontinued treatment differed significantly from those who did not; the latter initially used the drug less frequently (less than once per month), did not have a regular sexual partner or had a poor relationship with their sexual partner, and reported a decline in libido during use of the drug. The findings suggest that I-C papaverine, although effective in treating impotence, is not a panacea, and a large percentage of users (55% in our study) are likely to discontinue the drug within a relatively short period of time. PMID- 1742711 TI - Long-term psychiatric treatment. AB - Is long term psychiatric care superfluous? Can it be provided by non medical therapists? This paper examines this question from the perspective of one patient who was in therapy for 20 years. PMID- 1742712 TI - Adolescent murderers. AB - Clinical, developmental and environmental factors were retrospectively studied in 14 adolescent murderers who had been referred to a forensic psychiatric clinic over an 11 year period. Results of these analyses were compared with findings from previous reports. The majority of subjects came from split families. There was a greater than expected degree of psychiatric illness in the adolescents. Previous psychiatric contact, antisocial behaviour and substance abuse were common among these adolescents. A tentative profile of adolescents who are likely to commit murder can therefore be drawn up, which may suggest direction for preventive action and rehabilitation. PMID- 1742713 TI - Establishing a model for care in schizophrenia: one program's experience. AB - Unified service systems for the chronic mentally ill are frequently proposed yet rarely implemented. This paper presents a program developed specifically to meet the needs of young people with schizophrenia and their families. The program's evolution and design, from its origins in a hospital to its eventual base in the community, are described. The implications of a clinical teaching unit affiliated with a university are outlined. The experience of a typical patient and his family provides a view from a clinical context. Hypotheses arising from this case study point to future empirical work in the development of model programs in the care of the long term mentally ill. PMID- 1742714 TI - Consent to treatment: loophole in the Ontario Mental Health Act. AB - The issue of using substitute consent to obtain treatment for patients who are not competent to consent to treatment is complex. The authors present a case which illustrates that patients may delay treatment for extended periods of time by repeatedly challenging their incompetency status. The authors present proposals to change the present system. PMID- 1742715 TI - Organic dissociative syndrome associated with antimigraine pharmacotherapy. AB - This report describes an acute organic brain syndrome with a fugue-like state in association with antimigraine pharmacotherapy. The differential diagnosis of: 1. possible psychotoxic effects of the combination of propranolol, imipramine, and butalbital; 2. confusional migraine with amnesia; and 3. psychogenic dissociation is considered. Although organically induced dissociative states are of clinical, neuropsychological and medico-legal significance, the DSM-III and DSM-III-R have specific categories only for dissociative conditions that are strictly psychogenic in origin. PMID- 1742716 TI - Educating physicians for contemporary responsibilities in the field of developmental disabilities. AB - In 1977, an academic division concerned with developmental disabilities was established in the Department of Psychiatry at Queen's University in Kingston, Ontario. This paper describes the division's educational programs for undergraduate and post-graduate students. Reference is made to the resources (i.e. faculty, practicum settings) and the curricula required. Both are considered in relation to published information on such endeavours. The contemporary public policy for shifting the care of persons with developmental disabilities from institutions to the community is noted. Successful implementation of this policy depends in part on preparing physicians to meet the challenges of providing medical and psychiatric care in mainstream health care services. PMID- 1742717 TI - A first episode of mania after age 80. AB - The case of a patient whose first episode of mania (DSM-III-R diagnosis) occurred after age 80 is presented; the patient had no previous psychiatric illness. Diagnostic and therapeutic issues are discussed with special regard to features of mania in old age, secondary mania (organic mood syndrome), pseudodementia, MHPG excretion and carbamazepine treatment. PMID- 1742718 TI - Musical hallucinations: report of two unusual cases. AB - Two elderly patients with musical hallucinations are described. In the first case, the musical hallucinations were precipitated by the administration of benzodiazepines. The symptoms in the second case resembled those described in cases of visual hallucinosis (Charles Bonnet syndrome) in the elderly. Issues related to the presentation and course of musical hallucinations are discussed. PMID- 1742719 TI - A case of pseudologia fantastica with antisocial personality disorder. AB - A case of pseudologia fantastica with antisocial personality disorder is described. It is important to obtain previous admission records as early as possible so patients can be confronted with the discrepancies in their history. The concept of pathological lying is discussed. PMID- 1742720 TI - Body size estimation in characterizing dysmorphic symptoms in patients with body dysmorphic disorder. PMID- 1742721 TI - Hair loss associated with fluoxetine treatment. PMID- 1742722 TI - Genetic errors, cell proliferation, and carcinogenesis. PMID- 1742723 TI - Use of mentholated cigarettes and lung cancer risk. AB - Black males have higher age-adjusted lung cancer incidence rates compared to white males, and blacks of both sexes have higher rates of increase in lung cancer incidence over past decades. The majority of black smokers smoke mentholated cigarettes. These observations prompted us to assess the effect of smoking mentholated cigarettes on lung cancer risk, using data from a hospital based case-control study of tobacco-related cancers. Analysis was restricted to current cigarette smokers and was carried out on 588 male lung cancer cases and 914 male control patients and on 456 female lung cancer cases and 410 female controls interviewed between 1985 and 1990. The prevalence of menthol usage did not differ between cases and controls of either sex. No significant association was observed between either short-term (1-14 years) or long-term (15+ years) menthol use and lung cancer in logistic regression analyses adjusting for covariates. For specific histological types of lung cancer there was no indication of an association with menthol usage. PMID- 1742724 TI - Identification of nuclear matrix proteins in the cancer and normal rat prostate. AB - The nuclear matrix is the structural component of the nucleus that determines nuclear morphology and organizes the DNA in a three-dimensional fashion that is tissue specific. Previously, some of the nuclear matrix proteins have been reported to be both tissue and cell type specific and are altered with the state of differentiation and transformation. This study demonstrates that the nuclear matrix is specific for the individual lobes of the normal rat prostate and that the nuclear matrix undergoes changes in protein composition in the Dunning prostate cancer tissue. Additionally, in the Dunning rat prostate adenocarcinoma cell lines, there is a range of tumor phenotypes and the nuclear matrix varies in composition in each tumor cell type. These differences in the nuclear matrix proteins are associated with quantitative changes in nuclear morphology that form the pleiomorphic state of the cancer nucleus. PMID- 1742725 TI - Dysregulation of parathyroid hormone-like peptide expression and secretion in a keratinocyte model of tumor progression. AB - Using a human keratinocyte model of tumor progression, we have examined the regulation of gene expression and secretion of a parathyroid hormone-like peptide (PLP) that has been implicated in the pathogenesis of hypercalcemia in cancer. A rapid and transient induction of PLP mRNA in response to serum stimulation was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells; however the dose dependent increases were greater in HPK1A than in HPK1A-ras. Significant inhibition of this induction was noted with the addition of 1,25-dihydroxyvitamin D3 at a lower concentration in HPK1A than in HPK1A-ras. Amino-terminal PLP immunoreactivity and bioactivity correlated well (r = 0.98) when measured in conditioned medium. In the absence of mitogenic stimuli, malignant keratinocytes (HPK1A-ras) secreted significantly more PLP than established (HPK1A) keratinocytes. However, in response to increasing concentrations of epidermal growth factor and fetal bovine serum, PLP release was far greater from HPK1A (maximum 13 x basal) than from HPK1A-ras (maximum 3 x basal) cells. In addition, 1,25-dihydroxyvitamin D3 was more effective in inhibiting both basal and stimulated PLP secretion in HPK1A than in HPK1A-ras cultures. Reduction of extracellular Ca2+ from 2.0 mM to 0.5 mM appeared to be more effective at an early time point in reducing PLP secretion from the established cells compared with the malignant cells. These studies therefore demonstrate a progressive dysregulation of PLP expression and secretion in human keratinocytes in the transformation from established to malignant phenotype and may have important implications for understanding the pathogenetic mechanisms involved in vivo in the development of hypercalcemia in cancer. PMID- 1742726 TI - Differential expression of bcl2 protooncogene in neuroblastoma and other human tumor cell lines of neural origin. AB - The bcl2 protooncogene was originally discovered because of its involvement in t(14;18) chromosomal translocations frequently found in non-Hodgkin's lymphomas. The expression of this gene is reported to be highly tissue specific, with bcl2 mRNAs being readily detectable only in hematolymphoid tissues and brain. To explore the possible involvement of bcl2 in neural tumors, we surveyed a variety of tumor cell lines for the presence of the p26-BCL2 protein by immunoprecipitation and immunoblotting methods. Very high levels of BCL2 protein were found in three of nine neuroblastoma (NB) cell lines examined; these levels of p26-BCL2 were comparable to lymphoma cell lines that contain a t(14;18). Despite the impressive relative amounts of BCL2 protein, however, no structural alterations or changes in the methylation status of bcl2 genes were detected in these NB cell lines by conventional Southern blotting. Of the other NB cell lines surveyed, three contained intermediate levels of BCL2 and another three cell lines had little or no detectable BCL2 protein, raising the possibility that determination of relative levels of BCL2 protein may help to segregate neuroblastomas into groups with different biological and clinical characteristics. BCL2 protein levels were not influenced by induction of neuronal differentiation with nerve growth factor in two of the two cell lines examined [SH-SY5Y (high BCL2); GICAN (low BCL2)] and did not correlate with N-MYC gene amplification or expression of nerve growth factor receptors. NB cell lines that contained little or no detectable BCL2 protein, however, tended to contain significant proportions of flat epithelioid cells, whereas bcl2-expressing cell lines were composed primarily of neuronal-like cells, suggesting that expression of this protooncogene correlates with the differentiation characteristics of these tumor cell lines. In addition to NBs, lower levels of BCL2 protein were also found in a variety of other neural crest-derived tumors and tumor cell lines, including some neuroepitheliomas, Ewing's sarcomas, neurofibromas, and melanomas. With regard to tumors of central nervous system origin, bcl2 expression was absent from most medulloblastomas but was detected at moderate to low levels in a retinoblastoma and some glioblastoma multiforme cell lines. Taken together, these findings imply that bcl2 protooncogene expression is differentially regulated within the various lineages of cells that give rise to the nervous system. PMID- 1742727 TI - Photoreactivation of ultraviolet radiation-induced skin and eye tumors of Monodelphis domestica. AB - Chronic exposure of the opossum Monodelphis domestica to UV radiation (UVR) leads to the formation of cutaneous and corneal tumors. Groups of shaved opossums were exposed 3 times/week to: (a) UVR alone; (b) UVR followed immediately by 1 h of photoreactivating light (PRL) (320-700 nm); (c) 1 h of PRL followed by UVR; and (d) 1 h of PRL alone. Exposures were terminated after 70 weeks of treatment. Analysis of data plotted as probability of tumor formation versus weeks from first exposure shows that post-UVR exposure to PRL significantly (P less than 0.005) delayed the time to appearance of cutaneous tumors from a 50% probability of tumor formation at 73 weeks for those animals exposed to UVR alone to 128 weeks for those animals exposed to PRL after UVR. Pre-UVR exposure to PRL delayed the appearance of tumors by 6 weeks when compared to the UVR alone group, but the difference between the two groups was not statistically significant. The yield (number of tumors/surviving animal) of cutaneous tumors at 70 and 110 weeks following initiation of treatments also was significantly less in those animals exposed to PRL after, but not before, UVR. Based on the specificity of the PR repair pathway to act only on pyrimidine dimers, these results suggest that dimers are involved in the induction of cutaneous tumors. The results obtained with the induction of corneal tumors are more difficult to interpret. While exposure to PRL significantly delayed the appearance of corneal tumors, the magnitude of the effect was the same regardless of whether the PRL was given before or after each UVR exposure. PMID- 1742728 TI - Relationship between DNA cross-links, cell cycle, and apoptosis in Burkitt's lymphoma cell lines differing in sensitivity to nitrogen mustard. AB - We surveyed 11 Burkitt's lymphoma cell lines for chemosensitivity to nitrogen mustard (HN2) in order to determine whether any simple correlates to cytotoxic response might be revealed. The lines tested varied over a 5-fold range in concentration of HN2 required to inhibit tumor cell growth by 50%. Drug sensitivity correlated neither with continental origin of tumor, growth fraction, presence of Epstein-Barr virus, nor with the precise locations of (8;14) translocation breakpoints. Furthermore, contrary to experience with other cell lines, no simple correlation was found between the HN2 sensitivity of the four most divergent lines (low sensitivity, CA46 and MC116 cells; high sensitivity, Namalwa and JLP119 cells) and exposure to DNA cross-links (area under the DNA cross-linking-versus-time curve). In addition, we found similar extents of gene specific HN2-induced damage in the native and translocated c-myc alleles of CA46 and JLP119 cells. At equimolar HN2 treatment, CA46 cells exhibited a profound arrest in G2M phase, while JLP119 cells exhibited prolonged S-phase delay. This suggested that despite similar DNA cross-link exposure, JLP119 cells were less able to complete DNA replication while repair was in progress. As cell cycle distribution returned to near normal, JLP119 cells exhibited DNA degradation characterized by oligonucleosome-sized DNA fragments prior to cell membrane disintegration. Our findings indicate that HN2-sensitive Burkitt's lymphoma cells may be more susceptible to delay in S phase for a given frequency of DNA cross links and that prolongation of S phase correlated with apoptotic cell death. PMID- 1742729 TI - Measurement of serum L-asparagine in the presence of L-asparaginase requires the presence of an L-asparaginase inhibitor. AB - The antileukemic activity of L-asparaginase (ASNase), an important component of therapy for acute lymphoblastic leukemia, is thought to result from depletion of serum L-asparagine (Asn). In studies of the pharmacological effects of ASNase, investigators have reported prolonged reduction in the serum concentration of Asn after the administration of ASNase. Such measurements may not be valid because ASNase present in the blood sample may hydrolyze Asn before its determination. We examined recovery of [U-14C]Asn from blood samples with and without various concentrations of added ASNase. In the presence of greater than or equal to 0.01 IU/ml of ASNase, the amount of [U-14C]Asn recovered was less than 15% of that without ASNase. Utilizing this assay, we studied the effect of 2 known inhibitors of ASNase in an attempt to improve Asn recovery. In the presence of aspartic beta semialdehyde (ASA), or 5-diazo-4-oxo-L-norvaline (DONV), and up to 1.0 IU/ml ASNase, Asn levels remained at greater than 90% of control. ASA prevented the hydrolysis of exogenous Asn in blood samples drawn from patients after ASNase injection. We also developed a method to determine Asn in serum utilizing high pressure liquid chromatography. Using this method, we found that the Asn level was greater than 90% of a normal level in the presence of 40 mM DONV and 1.0 IU/ml ASNase. Examination of serum from 4 patients treated with ASNase showed that Asn is detectable 7-19 days sooner when DONV is present in the blood collection system than in its absence. We conclude that: (a) as little as 0.01 IU/ml ASNase can hydrolyze Asn added to blood; (b) continued hydrolysis of Asn by ASNase ex vivo can result in falsely low serum Asn measurements; (c) ASA or DONV present in the collection tubes obviates the problem of continued ASNase activity; and (d) the degree and duration of Asn depletion after ASNase therapy is much less than previously believed. Thus, for accurate measurements of the duration and degree of Asn depletion by ASNase, an ASNase inhibitor such as ASA or DONV should be present in the blood collection system. PMID- 1742730 TI - Metastatic potential and substrate dependence of cell motility and attachment in the Dunning R-3327 rat prostatic adenocarcinoma model. AB - Cancer cell motility has been associated with metastatic potential of sublines of the Dunning R-3227 rat prostatic adenocarcinoma model. However, three sublines of high motility lacked the capacity for metastasis. In all previous works, motility has been studied upon plastic and only upon attached cells at least 18 h after gravity plating. We studied two highly motile sublines; MAT-LyLu metastasizes to lungs and lymph nodes whereas PIF-1 metastasizes rarely. We compared the motility and attachment capability of cells from the Dunning model in serum-free media upon plastic, glass, laminin, type IV collagen, fibronectin, and elastin to determine whether study upon more physiological surfaces could better explain the discrepancy in metastatic capability observed in vivo. In the high-motility low metastatic PIF-1 and high-motility high-metastatic MAT-Lylu sublines, membrane ruffling, pseudopodal extension, and cellular translation upon plastic in serum free media were reduced (P less than 0.0001) by 33 and 31, 70 and 60, and 77 and 65%, respectively. When returned to serum-containing media, biological characteristics (histology, chromosomal number, growth rate, host survival, and metastatic potential) were unchanged. Motility was affected by substrate (analysis of variance, P less than 0.05); however, no consistent pattern of enhancement or detriment occurred in any substrate across both sublines. When motility was compared between sublines, membrane ruffling and cellular translation were relatively unaffected by substrate, whereas pseudopodal extension was altered significantly by different substrates. However, upon individual substrates, no significant differences in motility existed between the two sublines to resolve the inconsistency of high-motility but low-metastatic potential in the PIF-1 subline. Therefore, we examined cell attachment, since in order for a metastatic cell to be motile upon substrate, it must first attach to it. Percentage of 10(5) cells attached was determined in serum-free media with the use of a cell counter after 1, 2, 4, 8, and 16 h on plastic and plastic coated with laminin, fibronectin, elastin, or type IV collagen. Cell attachment increased with time (P less than 0.05) on all substrates for MAT-LyLu (r = 0.95) and PIF-1 (r = 0.98). Attachment of MAT-LyLu cells was impaired by fibronectin and enhanced by elastin, laminin, and type IV collagen compared to plastic at all time points.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742731 TI - DNA damage and differential cytotoxicity produced in human carcinoma cells by CC 1065 analogues, U-73,975 and U-77,779. AB - U-73,975 (U-73) and U-77,779 (U-77), two analogues of the cyclopropylpyrroloindole antitumor antibiotic CC-1065, are promising novel chemotherapeutic agents which are known to alkylate the N3 position of adenine in a sequence-selective manner. The concentration of U-73 required to produce a 1 log cell kill in 6 human tumor cell lines varied from 20-60 pM. U-77 was more cytotoxic than U-73, with the concentrations required for a 1 log cell kill ranging from 1-20 pM. The cytotoxicity of U-73 and U-77 was found to be independent of the guanine O6-alkyltransferase phenotype. The sensitivity of the BE and HT-29 human colon carcinoma cells was increased when the time of drug exposure was increased from 2 to 6 h. DNA interstrand cross-links, as measured by the technique of alkaline elution, could only be detected when HT-29 or BE cells were exposed to extremely high concentrations of U-77 for 6 h. No other forms of DNA damage were detected in genomic DNA with either compound. U-77 was also found to induce DNA interstrand cross-links in naked DNA, as measured by an agarose gel method. The rate of interstrand cross-linking was extremely rapid with the "second-arm" of the cross-link being completed within 2 h. The mechanism by which these cyclopropylpyrroloindole compounds elicit their cytotoxicity, however, remains to be elucidated. PMID- 1742732 TI - Flavone acetic acid directly induces expression of cytokine genes in mouse splenic leukocytes but not in human peripheral blood leukocytes. AB - Flavone-8-acetic acid (FAA) is a flavonoid drug that augments mouse natural killer activity, induces cytokine gene expression, and synergizes with recombinant interleukin 2 for the treatment of murine renal cancer. However, FAA has been largely inactive in human clinical trials. In the present study we investigated the ability of FAA treatment to directly induce cytokine mRNA expression in total mouse splenic leukocytes and selected leukocyte subsets, as well as in total human peripheral blood leukocytes. Analysis of RNA isolated from FAA-treated mouse splenic leukocytes demonstrated that treatment with greater than or equal to 100 micrograms/ml of FAA induced expression of tumor necrosis factor alpha (TNF-alpha) mRNA by 1 h and induced maximal expression of TNF-alpha, alpha-interferon, and gamma-interferon mRNA within 3 h. The expression of all cytokine genes was diminished by 6 h. Interferon biological activity was detected in the supernatants of mouse splenic or peripheral blood leukocytes after treatment with FAA. These results correlate well with the previously reported induction of cytokine mRNA genes and biological activity by FAA in vivo. In contrast, FAA did not induce detectable mRNA expression or cytokine protein secretion by human peripheral blood leukocytes under similar conditions. These results demonstrate that FAA can directly stimulate cytokine gene expression in mouse but not in human leukocytes. Further studies performed with highly purified positively selected mouse CD4+ or CD8+ splenic T-lymphocytes, as well as purified B-cells, demonstrated that the FAA-induced expression of gamma-interferon mRNA was mainly induced in the CD8+ lymphocyte subset. alpha-Interferon mRNA was expressed largely in the B-cell population, while TNF-alpha mRNA was induced in all leukocyte subsets tested. Therefore, these results suggest that the immunomodulatory effects of FAA in mice are direct, but different cytokines are induced from different leukocyte subsets. Further, the data suggest that flavonoid compounds or analogues that stimulate cytokine gene expression in human cells might be therapeutically active in cancer patients. PMID- 1742733 TI - Factors influencing mutation at the hprt locus in T-lymphocytes: women treated for breast cancer. AB - Forty-nine women with breast cancer were enrolled in a prospective, longitudinal study of the genetic damage caused by treatment. Assays of mutant frequency at the hprt locus in peripheral blood lymphocytes were performed at approximately 6 month intervals for 2 years. Treatment consisted of surgery alone or additional tamoxifen, radiotherapy, or chemotherapy in various combinations. At 6 months, there was an elevation of mean mutant frequency compared to initial values (P = 0.004) which persisted for as many as 2 years. A significant elevation at 6 months occurred only in the group of women who received combination chemotherapy (P = 0.005). Within this group, 5 of 15 patients had striking elevations of mutant frequency following chemotherapy (greater than 3 SD). Three of these 5 women had serum folate levels in the deficient range, while only one of 9 patients with lesser responses to chemotherapy were folate deficient. The change in mutant frequency after chemotherapy was inversely related to serum folate levels (P = 0.05) and to the number of years of smoking cigarettes (P = 0.01). We conclude that of the various modalities used to treat breast cancer, only chemotherapy was accompanied by a high risk of somatic mutation. A subset of patients manifested substantial increases in mutant frequency, often in association with low serum folate levels. PMID- 1742734 TI - Expression of HSP-28 and three HSP-70 genes during the development and decay of thermotolerance in leukemic and nonleukemic human tumors. AB - Leukemic cells appear to develop less thermotolerance and then to lose their thermotolerance more rapidly than do other tumor cell lines. The reason for this phenomenon is not known. After heat shock (or other environmental stresses), mammalian cells preferentially synthesize a set of proteins known as heat shock proteins (HSPs). HSP-28 and the various isoforms of HSP-70 have been suggested as being responsible for the development of thermotolerance. In these studies, we have attempted to determine by their expression with HSPs positively correlate with the development and decay of thermotolerance and whether the expression of these genes could explain the differing thermotolerance response observed between leukemic and nonleukemic tumor cells. Polymerase chain reaction was used to detect the expression of HSP-28 and several HSP-70 genes. Our data indicate that the expression of all three heat-inducible HSP-70 genes, 70A (Hunt and Morimoto, Proc. Natl. Acad. Sci. USA, 82: 6455-6459, 1985), 70B (Voellmy et al., Proc. Natl. Acad. Sci. USA, 82: 4949-4953, 1985), and 70B' (Leung et al., Biochem J., 267: 125-132, 1990) correlate with the development and decay of thermotolerance in nonleukemic tumor cell lines after heat or arsenite treatment. HSP-28 (Hickey et al., Nucleic Acids Res., 4: 4127-4145, 1986) failed to correlate with thermotolerance development; it was not induced after 45 degrees C primary heat shock. In leukemic cells, however, none of the HSPs were induced for extended periods of time. The lack of coordinate expression of HSP genes in cells of myeloid origin may explain the poor induction and maintenance of thermotolerance that is observed in these cells. PMID- 1742735 TI - Alterations of the p53 tumor suppressor gene during mouse skin tumor progression. AB - The two-stage murine skin tumorigenesis model is widely used to study the development of squamous cell neoplasias. We have investigated expression of the p53 and retinoblastoma tumor suppressor genes in eight murine skin tumor cell lines of varied histopathology and malignant potential, in seven in vivo-derived clones from these cell lines, and in 39 primary short-term cultures of similarly induced skin tumors at various stages of tumor progression. One squamous cell carcinoma cell line and three more malignant clones derived from it revealed mutations of the p53 protein by immunoprecipitation analyses despite normal-sized p53 transcripts. Sequence analysis identified the nature of the point mutations in these lines, a G----C transversion in codon 132. Mouse retinoblastoma transcripts and protein were unaltered in all the cell lines examined. Among short-term cultures of skin tumors, the p53 gene appeared normal in all papillomas and early well-differentiated carcinomas by Southern and immunoprecipitation analyses. In contrast, four of eight tumors from later stages of promotion (50-60 weeks) possessed alterations in p53, including loss of the p53 product, and loss of immunoreactivity with a murine-specific antibody recognizing only wild-type p53 protein. Loss of heterozygosity at the p53 locus was similarly observed in several more malignant tumors from later stages of promotion. In contrast retinoblastoma expression was normal regardless of the stage of promotion or histological grade of the tumor. Direct sequence analyses of exons 5 through 8 of the p53 gene in eight advanced murine skin tumors revealed a 25% incidence of p53 mutations. These point mutations were located in codons 245 and 263. Collectively, these data indicate that alterations in the p53 gene occur in 25 to 50% of murine skin tumors induced by the two-stage tumorigenesis protocol and are later events in murine skin tumor progression. Moreover, these alterations are associated with tumors possessing a more malignant and/or poorly differentiated phenotype. PMID- 1742736 TI - Disruption of cellular energy balance by suramin in intact human prostatic carcinoma cells, a likely antiproliferative mechanism. AB - The antiparasitic drug, suramin, has antiproliferative effects in human carcinoma cells. It has been suggested that this occurs through blockade of growth factor receptor interactions. Three types of evidence that suramin rapidly inhibits cellular respiration or disrupts cellular energy balance in intact cells of the human prostate carcinoma cell line, DU145, are presented. Beginning at approximately 10(-4) M, suramin rapidly causes dose-dependent inhibition of tetrazolium conversion by mitochondrial dehydrogenases in intact cells, demonstrating an inhibition of respiration. This effect is reversed by exchange with suramin-free media but not by pretreatment with serum, epidermal growth factor, insulin-like growth factor I, acidic and basic fibroblast growth factors, or calcium. Rhodamine 123 (10 micrograms/ml) uptake by mitochondria in intact DU145 cells is inhibited in the presence of 10(-3) M suramin. Treatment with 10( 4)-10(-3) M suramin causes the loss of rhodamine 123 from cells with mitochondria prestained with rhodamine 123, indicating that suramin is acting as an ionophore or respiratory poison. Also shown by electron microscopy are progressive toxic changes in mitochondria of DU145 cells within 1 h after treatment with 10(-4) M suramin. These data indicate that in intact DU145 cells 10(-4) M suramin rapidly disrupts cellular energy balance or respiration as seen by three studies of mitochondrial state. Disruption of energy balance or respiration represents a likely antiproliferative mechanism, as is thought to be a primary mechanism for the action of suramin in parasitic diseases. This proposed mechanism of action for suramin can explain the most prominent observed clinical toxicities of nephrotoxicity, adrenal toxicity, coagulopathy, and demyelinating neuropathy. PMID- 1742737 TI - Camptothecin and its derivatives induce expression of the c-jun protooncogene in human myeloid leukemia cells. AB - We have recently demonstrated that certain camptothecin derivatives are effective agents in the treatment of human tumor xenografts in nude mice. While camptothecin and its derivatives are recognized as inhibitors of topoisomerase I, little is known about the effects of these agents on specific gene expression, particularly genes involved in growth control. The c-jun early response gene codes for a leucine zipper transcription factor. The present studies demonstrate that 20(S)-camptothecin, 9-amino-20(S)-camptothecin, and 9-nitro-20(S) camptothecin inhibit the growth of human U-937 myeloid leukemia cells and induce expression of the c-jun gene. c-jun transcripts were increased at 3 h and reached a maximum at 6 h of drug exposure. We also demonstrate that the induction of c jun gene expression by these agents occurs at the transcriptional level. H7, a nonselective inhibitor of protein kinase C, completely blocked c-jun expression in 20(S)-camptothecin-treated cells, while another protein kinase inhibitor, HA1004, had no detectable effect. Similar findings were obtained for other leucine zipper encoding genes, including jun-B. These results suggest that 20(S) camptothecin, 9-amino-20(S)-camptothecin, and 9-nitro-20(S)-camptothecin activate a cellular response involving the induction of early response genes. Finally, we demonstrate that induction of c-jun expression occurs in association with internucleosomal DNA fragmentation, a characteristic of programmed cell death. PMID- 1742738 TI - Antitumor activity of gamma-interferon in ascitic and solid tumor models of human ovarian cancer. AB - We have investigated the action of recombinant human gamma-interferon (rHuIFN gamma) against human ovarian cancer xenografts growing as ascites or as bulky solid i.p. tumors in nude mice. Both forms of the disease responded to i.p. rHuIFN-gamma with significant increases in mouse survival time, and in 2 of 3 ascitic models the mice were cured of peritoneal disease. The activity of rHuIFN gamma was dose and schedule dependent, and xenografts derived from 3 different patients showed a heterogeneity of response. Peak i.p. levels of rHuIFN-gamma in nude mice bearing multiple i.p. solid tumors were similar to those found in ovarian cancer patients receiving i.p. rHuIFN-gamma, but clearance was more rapid in the mice. Rat gamma-interferon had no antitumor activity at the same doses and schedules although it had some biological activity in the nude mice. Histological examination of treated tumors revealed increased necrosis and loss of cellular organization with large areas of hypocellular epithelial mucin. These changes were preceded by a fall in tumor tryptophan and a rise in tumor kynurenine. We conclude that rHuIFN-gamma has a direct dose related antitumor effect on ovarian cancer xenografts that is preceded by increased metabolism of tryptophan. PMID- 1742739 TI - Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma. AB - In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA 255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved. PMID- 1742740 TI - Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. AB - Melanoma-derived lipoprotein lipase inhibitor (MLPLI) is a factor purified from the conditioned medium of a human melanoma cell line, SEKI, which induced severe cachexia in tumor-bearing nude mice. Amino acid sequencing revealed that the amino-terminal portion was identical to that of leukemia-inhibitory factor (LIF). To determine whether MLPLI is actually LIF, the expression of LIF mRNA was examined in the SEKI melanoma cell line. Northern blot analyses revealed that the cell line displayed an intense hybridizable band with a molecular size of 3.8 kilobases, suggesting that MLPLI is identical to LIF. The relationship between the development of the cancer cachexia syndrome and the expression of LIF mRNA was examined in four melanoma xenografts, SEKI, G361, A375 and MEWO, in nude mice. SEKI- and G361-bearing nude mice developed cancer cachexia syndrome, and their body weights decreased by the 25th day after the transplantation to 73.6% and 73.8% of the control, respectively. A375- and MEWO-bearing nude mice, however, did not develop the syndrome. Northern blot analyses revealed that G361 as well as SEKI expressed a large amount of LIF mRNA, but A375 and MEWO did not, suggesting a close relationship between the expression of LIF mRNA and the development of the syndrome. These data support the concept that MLPLI, or LIF, plays an important role in the development of the cancer cachexia syndrome observed in melanoma-bearing nude mice. PMID- 1742741 TI - Isolation and characterization of human melanoma cell variants expressing high and low levels of CD44. AB - Variants of the human melanoma cell line LT5.1 were selected for high and low expression of the Mr 90,000 CD44 glycoprotein by using the Hermes-3 monoclonal antibody combined with fluorescence-activated cell sorting. Cells were single cell cloned and clones of CD44 high-expressing and CD44 low-expressing phenotype were isolated. The variants, which exhibited up to a 7-fold difference between high and low expression, have maintained a stable phenotype over a period of 3 months in tissue culture. Northern blot analysis of mRNA from the different clones showed correlation of levels of transcripts with fluorescence-activated cell sorting analysis data. Wound migration assays, utilizing the different clones, showed that the low-expressing clones manifested less motility than did cells showing high levels of CD44. Homotypic aggregation of cells was increased in those cells expressing high levels of CD44, and these variants were also better able to adhere to hyaluronate substrates. All of these activities were inhibited by the presence of anti-CD44 antibody. When injected i.v. into nu/nu BALB/c mice, the low-expressing clones gave significantly fewer lung nodules than the high-expressing clones, although the two variant types did not differ in their capacity to form s.c. tumors in similar mice. These results suggest that the CD44 molecule, possibly as a function of its activities as a hyaluronate receptor, may play a vital role in determining the fate of hematogenously disseminating melanoma cells. PMID- 1742742 TI - Liver cancer in transgenic mice carrying the human immunodeficiency virus tat gene. AB - Patients with the acquired immunodeficiency syndrome are at risk to develop a variety of different cancers. Based on epidemiological data, Kaposi's sarcoma and non-Hodgkin's lymphoma have been clearly associated with infection by the human immunodeficiency virus (HIV). Additional cancers such as basal cell and squamous cell carcinomas, melanoma, and hepatocellular carcinoma have also been reported to be associated with a diagnosis of acquired immunodeficiency syndrome. A direct causal role of HIV has yet to be established for any of these cancers. We now report that transgenic mice carrying the HIV tat gene develop a high incidence of hepatocellular carcinoma after a long latency and that these changes in the liver are likely to be initiated by extrahepatic growth signals from the tat expressing cells in these mice. We predict that as acquired immunodeficiency syndrome patients begin to respond to therapy and show prolonged survival, such "secondary" malignancies induced by HIV will become increasingly prevalent. PMID- 1742743 TI - Interstitial hypertension in superficial metastatic melanomas in humans. AB - Since 1950, several investigators have demonstrated that interstitial hypertension is a pathophysiological characteristic of experimental solid tumors. To date, interstitial fluid pressure (IFP) has not been measured in human tumors in situ. In this study we measured with the wick-in-needle technique the interstitial fluid pressure in superficial melanoma metastases (n = 12) in patients (n = 10) before and during systemic therapy. In the majority of tumors the pressure was found to be almost uniform, while in others it varied severalfold. The large variations in IFP in some tumors may be due to technical or biological factors. With the data obtained before and during therapy grouped, the mean IFP in melanoma lesions varied between 2 and 41 mm Hg with an overall mean of 14.3 +/- 12.5 (SD). IFP was found to be significantly higher (P less than 0.01) in large (22.8 +/- 13 mm Hg; n = 6) than in small (5.8 +/- 2mm Hg; n = 6) lesions. This study demonstrates that IFP can be measured in human tumors using the wick-in-needle technique and that the pressure in some of the large melanomas exceeds the values measured to date in rodent tumors or human tumor xenografts. The latter result suggests that caution must be exercised in extrapolating values of pathophysiological parameters from transplanted tumors to human tumors. PMID- 1742744 TI - Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response. AB - Elevated tumor interstitial fluid pressure (IFP) is believed to be responsible, at least in part, for the poor penetration and heterogeneous distribution of blood-borne therapeutic agents and nutrients in solid tumors. Using the wick-in needle technique, IFP was measured in human patients with squamous cell carcinoma of the uterine cervix at the initial and final stages of fractionated external beam radiotherapy. Mean IFP values ranged from 10 to 26 mm Hg with an overall mean of 15.7 +/- 5.7 (SD) mm Hg in stage IIB and IIIB tumors (n = 12) and from 0 to 3 mm Hg in normal cervix (n = 3). IFP decreased in some patients with therapy while in others it increased. The changes in IFP values agree well with the clinical response to radiotherapy (n = 7, P less than 0.05). Oxygen tension, measured in selected tumors (n = 3) with polarographic oxygen microelectrodes, inversely correlated with IFP. These results show for the first time that the IFP in human cervical carcinomas is elevated, and that it can be lowered in some tumors using fractionated radiation therapy. These findings also suggest that IFP values may provide an indication of tumor oxygenation and that IFP modifications could be prognostic indicators of radiation response. PMID- 1742745 TI - Differential regulation of the stability of cyclic AMP-dependent protein kinase messenger RNA in normal versus neoplastic mouse lung epithelial cells. AB - Neoplastic mouse lung epithelial cells contain greatly diminished activity, protein, and mRNA for the type I isozyme of cyclic AMP-dependent protein kinase (PKA I), while expression of the type II isozyme (PKA II) is similar to that of normal lung cells. A time course of PKA mRNA content in transcriptionally inhibited cells indicated that most PKA mRNAs are more stable in the neoplastic E9 cell line than in related nontumorigenic C10 cells. To address the basis of this differential stability, we treated both cell lines with cycloheximide, an inhibitor of protein synthesis, in the presence or absence of the transcriptional inhibitor, 5,6-dichloro-1-b-ribofuranosyl-benzimidazole (DRB). The rate of PKA II regulatory subunit alpha mRNA decay in the presence of DRB was unaffected by cycloheximide treatment in E9 cells but decreased upon the addition of cycloheximide to DRB-treated C10 cells. The combination of these two agents markedly destabilized PKA II mRNAs (PKA catalytic subunit alpha and PKA II regulatory subunit alpha) relative to DRB treatment alone in neoplastic E9 cells, causing them to decay at a rate equal to that in C10 cells. PKA II mRNA may be specifically stabilized by a protein with a relatively short half-life in neoplastic E9 cells. These results suggest the involvement of tumor-specific factor(s) in the regulation of PKA mRNA stability, a potential mechanism for conferring the observed differential responsiveness of normal and neoplastic lung cells to cyclic AMP. PMID- 1742746 TI - Rearrangements on chromosome 11q23 in hematopoietic tumor-associated t(11;14) and t(11;19) translocations. AB - We previously demonstrated that the breakpoint of t(11;14)(q23;q32) in the RC-K8 B cell lymphoma cell line lies between CD3 and THY1/ETS1 on chromosome 11q23, and we cloned this region and named it the rck locus. Pulsed-field gel electrophoresis showed that the rck probe B (distal to the breakpoint) and the porphobilinogen deaminase (PBGD) probe detect the same germ line band and also the same rearranged band when DNA from RC-K8 cells was digested with NotI enzyme. Furthermore, Southern blot analysis with somatic cell hybrids showed that the PBGD gene moved to the 14q+chromosome, which confirmed PBGD to be more distal to the centromere than the rck locus. These data allowed us to construct the following order of genes: 11 cen-q23-CD3-rck-PBGD-THY1/ETS1. In this study, three infantile leukemia cell lines with t(11;19)(q23;p13) translocation were also analyzed by pulsed-field gel electrophoresis. CD3D probe detected the rearranged bands in DNA from two of them after digestion with NotI and SacII enzymes, demonstrating that the breakpoints of both cell lines were estimated to be within 360 kilobases of CD3D. PMID- 1742747 TI - Clinical aspects of the use of calcium antagonists in cerebrovascular disease. AB - Calcium antagonists may be useful for certain cerebrovascular conditions. In addition to producing a variable amount of cerebral vascular relaxation, high doses of some of these drugs may block calcium entry into neurons. Clinical trials in patients with vasospasm have clearly shown that calcium antagonists can improve outcome. Clinical trials in patients with acute stroke have been inconclusive, and have been flawed by delayed patient entry. Cardiovascular side effects may limit the safety and efficacy of calcium antagonists in acute stroke patients. Further investigation of early treatment with cerebroselective agents, possibly in conjunction with complementary therapies, is needed. PMID- 1742748 TI - Banisterine and Parkinson's disease. AB - It is of historical interest that 63 years ago Louis Lewin reported the use of a hallucinogenic compound prepared from the South American vine, Banisteria Caapi, to treat Parkinson's disease (PD). This psychoactive compound, named banisterine, proved to be identical to harmine, but 30 years were to pass before it was shown to be a reversible monoamine oxidase (MAO) inhibitor. The first reports of the use of banisterine to treat postencephalitic parkinsonism in 1929 created a stir in the popular press and banisterine was hailed as a "magic drug." Despite continued studies of the harmala alkaloids by other researchers, interest in the therapeutic value of these compounds vanished during the 1930's. The story of banisterine is reviewed because it was the first MAO inhibitor to be used in parkinsonism, and illustrates the historical role of psychoactive drugs in the development of effective therapies, and in elucidating the pathophysiology of PD. PMID- 1742749 TI - L-threonine in the treatment of spasticity. AB - Preclinical data indicate that the administration of the amino acid L-threonine increases glycine levels in rat spinal cord. In order to investigate glycinergic mechanisms in spasticity, and other signs of the upper motor syndrome, we gave 4.5 and 6.0 g/day of L-threonine to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. The response to treatment at the end of each 2-week period was based upon three measures: the physician's global impressions; the patients' global impressions; and semiquantitative ratings of strength, muscle tone, DTRs, walking, hopping, and running. Blood and CSF were collected during each treatment period for amino acid analyses. Based upon the severity rating scales, there was a statistically significant (p less than 0.02) decrease in motor impairment and spasticity during L-threonine administration compared to placebo treatment; significant treatment effects were not found on the physician's and patients' global impressions. Plasma and CSF levels of threonine increased significantly during L-threonine treatment but glycine levels did not change. These data indicate that L-threonine significantly suppressed the signs of spasticity even though the benefits were not clinically valuable. PMID- 1742750 TI - Interactions of sleep and clonidine on daytime prolactin secretion in humans. AB - The suppressive roles of adrenergic stimulation and rapid eye movement (REM) sleep on human prolactin (PRL) secretion are controversial. We examined the effects of sleep, clonidine (an alpha 2-adrenergic agonist), and their interaction on PRL secretion. Two groups of normal men (nine each) were studied in two morning sessions. Each group received either placebo or clonidine in both sessions. Subjects remained awake in the first session and in the next session they were asked to sleep for 3 h after the test dose was given. Blood samples were drawn at 30-min intervals and polysomnographic recordings were obtained at each session. PRL concentrations remained at baseline and no clonidine effect was detected while awake. PRL concentrations increased in placebo and clonidine groups during sleep. Despite significant suppression of REM sleep in the clonidine group, no differences were detected between the placebo and clonidine groups in peak PRL or mean PRL concentrations during the study. Also, no significant difference was detected in comparing PRL responses during non-REM sleep in both groups. The results suggest that alpha 2-adrenergic stimulation does not have a significant role in modulating human PRL secretion during sleep. PMID- 1742751 TI - Clenbuterol-induced tardive dyskinesia. AB - A 73-year-old man with a history of obstructive lung disease who received clenbuterol 20 mg b.i.d. over 5 years developed dyskinetic movements mainly of the respiratory muscles, closely resembling neuroleptic-induced dyskinesias. Despite drug withdrawal, abnormal movements persisted unchanged. Treatment with reserpine successfully controlled the dyskinetic movements. Clinicians should be aware of this potentially harmful effect of long-term clenbuterol therapy. PMID- 1742752 TI - Sublingual apomorphine in Parkinson's disease: a clinical and pharmacokinetic study. AB - The clinical response and the pharmacokinetic parameters of 3 mg subcutaneous (SC) and 30 mg sublingual (SL) apomorphine were compared in nine patients with Parkinson's disease. The magnitude of the motor responses (evaluated by tapping and walking tests and the Webster scale) was similar for SC and SL apomorphine. However, the onset to action was delayed after SL when compared with SC apomorphine. No significant difference was found in bioavailability (area under the curve: AUC) or peak plasma concentration (Cmax) between SC and SL apomorphine, whereas time to peak plasma concentration (Tmax) was shorter after SC apomorphine. Eight other patients were treated for a mean time of 4 months with SL apomorphine with a significant reduction in daily "off" hours. However, four of these eight patients developed stomatitis after some weeks of treatment. These results indicated that (a) pharmacokinetics parallel the clinical response to SL apomorphine, (b) SL apomorphine can reduce severe off periods in parkinsonian patients when used chronically, and (c) its long-term use is limited by a severe side effect (stomatitis). PMID- 1742753 TI - Orthostatic tremor: successful treatment with phenobarbital. AB - This article describes two patients with orthostatic tremor. The tremor affected the legs while standing and had a frequency of 14-16 Hz. We remark on the success of therapy with phenobarbital. PMID- 1742754 TI - Naloxone partly counteracts apomorphine side effects. AB - The effects of naloxone on side effects provoked by apomorphine (APO) administration in patients with parkinsonian syndrome have been studied. The group under study included eight patients with Parkinson's disease and four with parkinsonism who received 100 micrograms/kg s.c. APO acutely to test dopaminergic responsiveness. All patients were treated with 20 mg domperidone tablets t.i.d. and then for 2 consecutive days (in double blind fashion) were given a 2-hour i.v. saline infusion alone or with naloxone (8 mg) starting 30 min before APO administration. In both groups, naloxone delayed the appearance of sleepiness, and reduced the intensity of yawning, sleepiness, nausea, and vomiting as compared with saline. These findings indicate a potential usefulness of naloxone and other opioid antagonists in preventing acute APO side effects. PMID- 1742755 TI - Prolonged survival following the inadvertent intrathecal administration of vincristine: clinical and electrophysiologic analyses. AB - A 23-year-old man with a lymphoblastic lymphoma accidentally received 2.0 mg of vincristine intrathecally instead of intravenously. Although he underwent immediate CSF drainage, symptoms of an ascending myeloencephalopathy developed at 48 h. This progressed to coma, initially with a diffusely slow EEG, which evolved into alpha coma. He also developed a left frontal focus of epileptiform activity. He was transferred to our institution 1 month later. His court-appointed guardian refused to allow discontinuation of supportive treatment; therefore, the evolution of the disorder can be followed for 12 months. Although alpha coma remained the predominant pattern, some EEG evolution did occur, with a progressive decrease in amplitude being most prominent. An increase in amplitude in the 10th month was accompanied by the return of some nystagmoid eye movements. The patient's lymphoma then recurred, and further treatment was not attempted. This tragic case, in which transient exposure to a microtubular poison produced severe CNS toxicity, allows some insights into the mechanisms of alpha coma. PMID- 1742756 TI - Acute dystonia induced by sulpiride. AB - We report a 15-year-old boy who, after the administration of 100 mg i.v. of sulpiride, presented an acute dystonic reaction consisting of oculogyric crises, retrocollis, opysthotonus, and dystonic postures in the left arm and hand. The symptoms were reversed after the injection of biperiden. This side effect has not been described previously. Sulpiride can induce the same extrapyramidal adverse reactions as the classical neuroleptic drugs. PMID- 1742757 TI - Managed health care. PMID- 1742758 TI - Denver homeless being trained. PMID- 1742759 TI - Position statement on HIV/AIDS. PMID- 1742760 TI - Myocardial protection with verapamil during ischaemia and reperfusion: dissociation between myocardial salvage and the degree of ATP depletion during ischaemia. AB - STUDY OBJECTIVE: The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. DESIGN: In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusion and 60 min reperfusion. In separate groups of animals, haemodynamic measurements were taken at baseline, during ischaemia, and during reperfusion. Infarct size was determined by staining with triphenyltetrazolium chloride. EXPERIMENTAL MATERIAL: Female Sprague-Dawley rats were used (control group n = 25, experimental group n = 24). MEASUREMENTS AND MAIN RESULTS: Infarct size was significantly reduced in the verapamil group compared to controls: 9.9(SEM 2.3)%, n = 19 v 28.5(2.7)%, n = 19, p less than 0.001 (infarct % of left ventricular mass). Myocardial phosphocreatine and ATP levels were reduced to similar levels in both verapamil and control animals after 45 min ischaemia: 56.8(3.4)%, n = 10, v 61.4(1.8)%, n = 11 NS; 67.7(2.7)%, n = 10 v 69.7(2.9)%, n = 11, NS (% of baseline value). After 60 min reflow, there was significant recovery of phosphocreatine [91.1(4.2)% of baseline, p less than 0.05] and ATP [86.8(2.7)% of baseline, p less than 0.05] in the verapamil group, but no recovery of high energy phosphates in controls [66.3(2.8), NS; 69.6(2.7), NS]. The left ventricular systolic pressure, heart rate, rate-pressure product, and maximum rate of left ventricular pressure development were similar prior to ischaemia, and during ischaemia in both groups. There was an inverse correlation between infarct size and the degree of phosphocreatine recovery after 60 min of reperfusion (PCr recovery (%) = -0.99 x infarct size (%) + 101; r = 0.91; p less than 0.01; n = 14). Furthermore, in a separate group of animals (n = 9), there was a significant correlation between the size of the ischaemic area at risk and the degree of phosphocreatine decline after 15 min of coronary occlusion (PCr reduction (%) = 0.91 x risk area (%) + 5.6; r = 0.97; p less than 0.01). CONCLUSIONS: Pretreatment with verapamil extends the ischaemic time after which reperfusion results in myocardial salvage in this model of ischaemia and reperfusion. This protective effect is independent of the haemodynamic determinants of myocardial oxygen demand and the degree of ATP and phosphocreatine depletion during the ischaemic period. In this model of reversible ischaemia, 31P magnetic resonance spectroscopy is useful for quantitating both the size of the ischaemic region during coronary artery occlusion and infarct size after reperfusion. PMID- 1742761 TI - End systolic pressure-length relations in halothane anaesthetised dogs: effects of regional ischaemia and inotropic agents. AB - STUDY OBJECTIVE: The aim was to investigate the effects of regional myocardial ischaemia, calcium, and verapamil on (a) the hysteresis and (b) slope and length axis intercept of the left ventricular end systolic pressure-length relationship. DESIGN: Segment length in myocardium supplied by the left anterior descending coronary artery was measured in anaesthetised dogs using sonomicrometry. Three levels of regional myocardial ischaemia were produced by stenosis and occlusion of the left anterior descending artery (ischaemia 1, ischaemia 2, and occlusion). A snare placed around the descending thoracic aorta was used to obtain temporary aortic occlusions. SUBJECTS: Seven open chested mongrel dogs were used, weight 17 kg (range 16-20). MEASUREMENTS AND MAIN RESULTS: After abrupt release of temporary aortic occlusions, end systolic lengths were greater than before the occlusion in the normal myocardium. This hysteresis was abolished by regional myocardial ischaemia. However, hysteresis was insensitive to calcium and verapamil. The length axis intercept of the end systolic pressure-length relationship was increased during ischaemia 2, during coronary occlusion, and after administration of verapamil; its slope was increased after coronary occlusion. CONCLUSIONS: (1) Viscoelastic properties of the myocardium make a major contribution to hysteresis of the end systolic pressure-length relationship; and (2) the length axis intercept of this relationship is not constant and its slope does not appear to be a sensitive indicator of regional myocardial contractility during regional ischaemia. PMID- 1742762 TI - Reflection as a cause of mid-systolic deceleration of pulmonary flow wave in dogs with acute pulmonary hypertension: comparison of pulmonary artery constriction with pulmonary embolisation. AB - STUDY OBJECTIVE: The aim was to examine whether mid-systolic deceleration of the pulmonary flow wave occurred in acute pulmonary hypertension due to pulmonary artery constriction and pulmonary embolisation, and if so whether it was related to reflection. DESIGN: Various degrees of pulmonary hypertension were induced by both pulmonary artery constriction and pulmonary embolisation in dogs. During control periods and during pulmonary artery constriction and pulmonary embolisation, pulmonary flow and pulmonary artery pressure were recorded, and the forward and backward (reflected) flow waves were separated from the measured pulmonary flow wave by the method of Westerhof et al. MATERIALS: 20 adult mongrel dogs were used and 10 dogs qualified for analysis. The other 10 dogs, which died before both interventions were completed, were excluded. MEASUREMENTS AND MAIN RESULTS: During pulmonary artery constriction, a distinct mid-systolic deceleration of the pulmonary flow wave was observed in five of the 10 dogs, while during pulmonary embolisation, no mid-systolic deceleration was found in these five dogs. The distinct deceleration of the pulmonary flow wave was related to a steep fall and early negative peak in the backward flow wave. CONCLUSION: Mid-systolic deceleration of pulmonary flow wave is likely to be related to reflection. PMID- 1742763 TI - Enhanced circulating levels of neurally derived calcitonin gene related peptide in spontaneously hypertensive rats. AB - STUDY OBJECTIVE: Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator. The peptide is released from perivascular nerve endings and can normally be detected in the circulation. An attempt was made to determine the concentrations and partially characterise the immunoreactive forms of circulating CGRP in a genetically hypertensive rat strain, the "spontaneously hypertensive rat" (SHR) and its genetic control, Wistar-Kyoto (WKY). DESIGN: Immunoreactive plasma CGRP levels were measured using a highly sensitive carboxyl terminal specific CGRP radioimmunoassay together with high performance liquid chromatography. Plasma immunoreactive CGRP (i-CGRP) levels were also measured 6 h after intraperitoneal colchicine administration (10 mg.kg-1 body weight) to both groups of rats. EXPERIMENTAL MATERIAL: Eight SHR rats were compared with eight WKY rats, both groups aged 7 weeks. MEASUREMENTS AND MAIN RESULTS: Mean i-CGRP levels were threefold higher in the SHR group compared to controls, while plasma calcitonin levels were not different between the two groups. There was a significant correlation (Kendall's correlation coefficient, r = 0.57; p = 0.024) between i-CGRP levels and the mean systolic blood pressure (measured by the indirect tail cuff method) in SHR but not WKY rats. Similar profiles of i-CGRP were observed in both SHR and WKY rats, when acid-methanol extracts of pooled plasma were chromatographed under similar conditions. It was also confirmed that circulating CGRP in both SHR and WKY strains was derived from perivascular nerve endings, by demonstrating a complete abolition from plasma of previously detectable i-CGRP following the administration of colchicine. CONCLUSIONS: The study shows that CGRP is normally released from vascular nerve endings, and that high concentrations of the circulating peptide are found in hypertension. This might represent a mechanism to counteract the excessive vasoconstrictor influences that underly the development and maintenance of hypertension. PMID- 1742764 TI - Role of the endothelium in modulation of the acetylcholine vasoconstrictor response in porcine coronary microvessels. AB - STUDY OBJECTIVE: The aim was to investigate the role of the endothelium in modulating the acetylcholine response in porcine coronary microvessels and compare the results with simultaneously studied large coronary arteries. DESIGN: Coronary microvessels [104 (SEM 3.3) microns; range 38-150] were removed from fresh porcine hearts and studied in vitro during no flow constant pressure conditions. Endothelium derived relaxing factor (EDRF) activity and the role of the endothelium in modulating the acetylcholine response in microvessels was assessed by measuring changes in intraluminal diameter using a video tracking device. Large coronary arteries were simultaneously studied using conventional isometric ring techniques. EXPERIMENTAL MATERIAL: Fresh porcine hearts were obtained from a local slaughterhouse. MEASUREMENTS AND MAIN RESULTS: Acetylcholine was a potent vasoconstrictor (EC50 = 0.17 microM) of passively distended microvessels. The effects of EDRF were studied by either inactivation with haemoglobin or inhibition of EDRF synthesis with N-omega-nitro-L-arginine. Preconstricted microvessels exposed to either N-omega-nitro-L-arginine or haemoglobin constricted further, consistent with basal release of EDRF. Neither drug affected passively distended microvessels. The acetylcholine vasoconstrictor response was potentiated after exposure of microvessels to either drug. Atropine, but not indomethacin, blocked the acetylcholine response in microvessels. As with microvessels, acetylcholine was a vasoconstrictor (EC50 = 0.3 microM) of large coronary arteries. In contrast to microvessels, indomethacin antagonised acetylcholine vasoconstriction in vessels with intact endothelium. Bioassay experiments using indomethacin-treated large epicardial donor artery segments showed basal release of EDRF but no EDRF release in response to acetylcholine. CONCLUSIONS: The results show the microvessels and large coronary arteries are similar in their vasoconstrictor response to acetylcholine, that both release EDRF basally, and that vasoconstriction to acetylcholine is importantly modulated by the endothelium. In large arteries, acetylcholine does not stimulate EDRF release and, in contrast to microvessels, a cyclo-oxygenase product influences the vasoconstrictor action of acetylcholine. PMID- 1742765 TI - Influence of adenosine on the stimulatory effect of isoprenaline and insulin on myocardial contractility in vivo. AB - STUDY OBJECTIVE: In vitro investigations have indicated that adenosine can inhibit beta adrenergic stimulated increases in cardiac contractility. The present study was designed to determine the ability of adenosine to inhibit isoprenaline induced increases in contractility in vivo. Adenosine has been reported to exert its inhibitory effects on contractility by inhibiting adenylate cyclase. Thus, adenosine should have no effect on positive inotropic agents that act independently of adenylate cyclase. We therefore assessed the ability of this nucleoside to inhibit the positive inotropic effect of insulin, a hormone that exerts a positive inotropic effect independently of alterations in cyclic AMP. DESIGN: Saline or adenosine (10 mumol.ml-1) was infused into the circumflex artery at 1 ml.min-1 as a background. Isoprenaline (20 or 200 pmol.min-1) was infused into the artery during saline or adenosine infusion. The response to insulin was determined during hyperinsulinaemic euglycaemic clamp. SUBJECTS: 16 adult mongrel dogs were anaesthetised with pentobarbitone. Five dogs were used in isoprenaline studies, and 11 dogs in insulin studies. MEASUREMENTS AND MAIN RESULTS: Dogs were instrumented to obtain measurements of mean arterial blood pressure, heart rate, circumflex artery blood flow (Q), instantaneous left ventricular pressure, and posterior left ventricular wall thickness. We used the slope of the end systolic pressure-dimension relationship (Ees) as an index of myocardial contractility, previously shown to reflect changes in myocardial inotropic state independent of influence from afterload and preload. Left ventricular dP/dtmax was derived from left ventricular pressure with respect to time, and Ees was determined from left ventricular pressure and wall thickness. Neither adenosine, isoprenaline, nor insulin alone caused any significant changes in mean arterial pressure or heart rate. Adenosine caused a significant increase in Q. Both left ventricular dP/dtmax and Ees were significantly increased by either insulin or both doses of isoprenaline. Adenosine inhibited the increases in these indices caused by isoprenaline, but not those caused by insulin. CONCLUSIONS: Adenosine is capable of inhibiting the positive inotropic effect of isoprenaline in vivo. The results suggest that adenosine does not inhibit positive inotropic responses that act independently of the stimulation of adenylate cyclase. PMID- 1742766 TI - Changes in myocardial energy metabolism in elective coronary angioplasty. AB - STUDY OBJECTIVE: The aim was to investigate the effect of coronary angioplasty on myocardial energy metabolism, and to assure the safety of the procedure in patients with coronary heart disease. DESIGN: Before angioplasty a catheter was introduced into the coronary sinus. Blood samples were taken simultaneously from femoral artery and coronary sinus before balloon inflation, upon balloon deflation, and two minutes later, and arteriovenous differences in myocardial substrates, pH, PCO2, oxygen saturation, and adenosine catabolites were determined. PATIENTS: 14 patients with angiographically documented coronary artery disease with lesions in the left coronary artery suitable for elective coronary angioplasty were included in the study. RESULTS: During balloon inflation the positive femoroarterial-coronary sinus difference of lactate turned negative, from 0.21(SEM 0.05) mM to -0.10(0.11)mM, p less than 0.02. At the same time pH and PCO2 differences increased: from 0.04(0.00) U to 0.07(0.01) U, p less than 0.01, and from -1.15(0.10) kPa to -1.41(0.10) kPa, p less than 0.01, respectively. The changes were, however, transient and the arteriovenous differences in these metabolic variables rapidly returned towards preinflation levels after balloon deflation. The femoroarterial-coronary sinus concentration differences in glucose and free fatty acids became positive in coronary angioplasty. The energy state remained good during the procedure as assessed from the negligible net efflux of adenosine and its degradation products. CONCLUSIONS: Elective coronary angioplasty can be performed without any persistent derangements in myocardial metabolism, and may in fact lead to improvement of utilisation of some myocardial substrates. Lactate appears to be a more sensitive indicator of short term ischaemia than adenosine degradation products. PMID- 1742767 TI - Improvement in contractile recovery of isolated rat heart after cardioplegic ischaemic arrest with endogenous phosphocreatine: involvement of antiperoxidative effect? AB - STUDY OBJECTIVE: The aim was to attempt to get further insight into the mechanism of the cardioprotective action of phosphocreatine (PCr). DESIGN: Three experimental protocols were used: (1) The effect was examined of exogenous PCr (10 mmol.litre-1) on myocardial oxidative damage produced by H2O2 perfusion (90 mumol.litre-1) of isolated rat heart. (2) Isolated rat hearts were subjected to 35 min cardioplegic ischaemia followed by reperfusion. A control group was studied along with two PCr groups, one corrected for Ca2+ to compensate its binding with PCr (1.4 mmol.litre-1 CaCl2 in St Thomas's Hospital cardioplegic solution), and the other not (1.2 mmol.litre-1). (3) The effect was studied of PCr alone and in combination with the antioxidant tocopherol phosphate (0.1 mumol.litre-1) on contractile and metabolic recovery of isolated rat heart reperfused after 40 min cardioplegic ischaemia. EXPERIMENTAL MATERIAL: Studies were performed on hearts of 84 male Wistar rats, weighing 250-300 g. MEASUREMENTS AND MAIN RESULTS: (1) Oxidative stress resulted in irreversible contracture and impairment of sarcolemmal integrity revealed by using the transmembrane tracer ionic lanthanum. These effects coincided with the decrease of developed pressure from 116 (SEM 3) to 38(3) mm Hg and rate-pressure product from 498(13) to 165(16) mm Hg.s-1. The Ca2+ binding property of PCr was estimated experimentally and the stability constant of the complex CaPCr was found to be 35.4(0.7) mmol; from this the Ca2+ bound by PCr was calculated to be 14% in the experimental conditions used. Ca2+ concentration in K-H buffer containing PCr was increased to compensate its binding with PCr. PCr prevented H2O2 induced contracture, preserved sarcolemmal integrity, and attenuated H2O2 induced decrease in developed pressure and rate-pressure product [73(6) mm Hg and 340(28) mm H.s-1, respectively, p less than 0.05 compared with control]. (2) PCr reduced the diastolic pressure [29(10) v 68(10) mm Hg in control group at 30 min of reperfusion, p less than 0.05] and enhanced the developed pressure [81(10) v 46(10) mm Hg in controls, p less than 0.05] and rate-pressure product [325(44) v 158(40) mm Hg.s-1 in controls, p less than 0.05]. When CaCl2 was increased to 1.4 mmol.litre-1 the protective effect of PCr was not abolished. (3) PCr resulted in improvement of developed pressure [49(7) v 18(5) mm Hg in controls at 40 min of reperfusion, p less than 0.05] and rate-pressure product [184(27) v 71(20) mm Hg.s-1 in controls, p less than 0.05]. The degree of contractile recovery in the tocopherol group was almost the same as in the PCr group. Combined addition of PCr and tocopherol further increased the developed pressure and rate-pressure product to 72(4) mm Hg and 284(23) mm Hg.s 1, respectively. Similarly, PCr and tocopherol in combination provided substantial inhibition of creatine kinase release into perfusate, at 3.8(0.4) v 10.9(2.5) IU in controls, p less than 0.05. CONCLUSIONS: PCr decreases the vulnerability of myocardium to oxidative stress and ischaemic damage. These effects cannot be explained by PCr induced shifts in Ca2+ concentration. Protective effects of PCr and tocopherol are quantitatively additive, most probably due to their different mechanisms of action, and tocopherol may be effective in extending the ability of PCr to stabilise cell membrane structure. PMID- 1742768 TI - Reduction of experimental myocardial infarct size by oral administration of alpha tocopherol. AB - STUDY OBJECTIVE: The aim was to determine whether high dose dietary vitamin E could improve myocardial resistance to ischaemia and reperfusion. Vitamin E is an important physiological antioxidant which can be accumulated to high levels in the myocardium, without toxicity, by chronic dietary supplementation. DESIGN: Subjects were fed a standard laboratory feed and water ad libitum for 10 d, plus either d-alpha-tocopoheryl acetate 200 IU.kg-1.d-1 orally (vitamin E group), or no supplement (control group). The animals then underwent either 60 or 180 min of left anterior descending coronary artery ligation, followed by 6 h reperfusion. The area at risk was identified by colloidal carbon, and necrosis by triphenyl tetrazolium chloride and light microscopy. SUBJECTS: Studies were performed on New Zealand white rabbits weighing approximately 3.5 kg. MEASUREMENTS AND MAIN RESULTS: In the 60 min ligation study, the control group had 30.5 (SD 4.0)% necrosis of the area at risk but the vitamin E group had no necrosis (n = 5 per group, p less than or equal to 0.0001). In the 180 min ligation study, the control group had 74.1 (11.5)% necrosis of the area at risk whereas the vitamin E group had 23.1 (7.2)% (n = 5 per group, p less than or equal to 0.0001). CONCLUSIONS: High dose dietary supplementation with vitamin E can improve myocardial tolerance to ischaemia and reperfusion, significantly reducing myocardial infarct size. PMID- 1742769 TI - Failure of cyclo-oxygenase inhibition to protect against arrhythmias induced by ischaemia and reperfusion: implications for the role of prostaglandins as endogenous myocardial protective substances. AB - STUDY OBJECTIVE: It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model. DESIGN: Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane--aspirin (7 mg.kg-1), flurbiprofen (3 mg.kg-1), and sodium meclofenamate (2 mg.kg-1) with or without nafazatrom or dazmegrel--were given prior to a combined occlusion reperfusion insult, and the severity of resulting arrhythmias examined. MATERIAL: Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate +/- nafazatrom or dazmegrel n = 22. MEASUREMENTS AND MAIN RESULTS: None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasystoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg.ml-1] and prostacyclin [from 450(80) to 720(110) pg.ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg.kg-1 orally) or dazmegrel (3 mg.kg-1 intravenously), which when given alone are markedly protective, abolished this protection. CONCLUSION: The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance". PMID- 1742770 TI - Glutamic acid decarboxylase of embryonic avian retina cells in culture: regulation by gamma-aminobutyric acid (GABA). AB - 1. Retina-cell aggregate cultures expressed glutamate decarboxylase activity (L glutamate 1-carboxylase; EC 4.1.1.15) as a function of culture differentiation. 2. Glutamic acid decarboxylase (GAD) activity was low in the initial phases of culture and increased eight-fold until culture day 7, remaining high up to day 13 (last stage studied). 3. The addition of GABA to the culture medium 24 h after cell seeding almost totally prevented the expression of GAD activity. 4. In association with decreased enzyme activity, aggregates exposed to GABA did not display immunoreactivity for GAD, suggesting that GAD molecules were either lost from GABAergic neurons or significantly altered with GABA treatment. 5. Control, untreated aggregates showed intense GAD immunoreactivity in neurons. Positive cell bodies were characterized by a thin rim of labeled cytoplasm with thickest labeling at the emergence of the main neurite. 6. Heavily labeled patches were also observed throughout the aggregates, possibly reflecting regions enriched in neurites. 7. The GABA-mediated reduction of GAD immunoreactivity was a reversible phenomenon and could be prevented by picrotoxin. PMID- 1742772 TI - Cluster headache--course over ten years in 189 patients. AB - One-hundred-and-eighty-nine cluster headache patients, referred to Parma and Pavia Headache Centres between 1976 and 1986 with a disease duration of over 10 years, were interviewed about the course of cluster headache. They were classified as episodic (n = 140) or chronic (n = 49) cluster headache patients on the basis of course during the year of onset. Episodic patients showed the following outcome: maintenance of an episodic form (primary episodic form) in 80.7% of cases, shift towards a chronic form (secondary chronic form) in 12.9% and shift towards an intermediate pattern ("combined" form) in 6.4%. In chronic patients, cluster headache was still chronic (primary chronic form) at the moment of observation in 52.4% of cases, while it turned into an episodic form ("secondary" episodic form) in 32.6% and into a "combined" form in 14.3%. Nineteen patients (10%) had had no attacks for at least three years at the moment of examination. We can conclude from our data that: cluster headache is a disease of long duration, perhaps lifelong; episodic cluster headache tends to worsen; chronic cluster headache may easily turn into a better prognostic episodic form; prophylactic drugs are unable to induce recovery. The following factors seem related to a poor outcome: a later onset, the male gender and a disease duration of over 20 years for the episodic forms. PMID- 1742771 TI - Rhythmic regulation of retinal melatonin: metabolic pathways, neurochemical mechanisms, and the ocular circadian clock. AB - 1. Current knowledge of the mechanisms of circadian and photic regulation of retinal melatonin in vertebrates is reviewed, with a focus on recent progress and unanswered questions. 2. Retinal melatonin synthesis is elevated at night, as a result of acute suppression by light and rhythmic regulation by a circadian oscillator, or clock, which has been localized to the eye in some species. 3. The development of suitable in vitro retinal preparations, particularly the eyecup from the African clawed frog, Xenopus laevis, has enabled identification of neural, cellular, and molecular mechanisms of retinal melatonin regulation. 4. Recent findings indicate that retinal melatonin levels can be regulated at multiple points in indoleamine metabolic pathways, including synthesis and availability of the precursor serotonin, activity of the enzyme serotonin N acetyltransferase, and a novel pathway for degradation of melatonin within the retina. 5. Retinal dopamine appears to act through D2 receptors as a signal for light in this system, both in the acute suppression of melatonin synthesis and in the entrainment of the ocular circadian oscillator. 6. A recently developed in vitro system that enables high-resolution measurement of retinal circadian rhythmicity for mechanistic analysis of the circadian oscillator is described, along with preliminary results that suggest its potential for elucidating general circadian mechanisms. 7. A model describing hypothesized interactions among circadian, neurochemical, and cellular mechanisms in regulation of retinal melatonin is presented. PMID- 1742773 TI - Histamine receptors in the isolated human middle meningeal artery. A comparison with cerebral and temporal arteries. AB - The subtypes of histamine receptors mediating dilatation of human meningeal arteries have been tested in vitro, using "selective" antagonists, and compared with cerebral and temporal arteries previously examined. Dilatory responses were tested after preconstriction with prostaglandin F2 alpha. Both mepyramine and cimetidine caused a parallel shift to the right of the histamine concentration response curve, suggesting the presence of both H1- and H2-receptors. Combined treatment with mepyramine and cimetidine caused further displacement of the concentration-response curve to the right. Schild analysis indicated pA2 values of 6.3 for cimetidine and 9.8 for mepyramine in situations of near complete blockade of either of the receptors. Both H1- and H2-receptors seem of importance for the histamine-induced dilatation in meningeal arteries and neither appear to dominate. The data considered in conjunction with our previous findings support the finding that experimental histamine-induced headache due to vasodilatation is intracranial of origin. PMID- 1742774 TI - The similarities and differences of migraine with aura and migraine without aura: a preliminary study. AB - A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects. PMID- 1742775 TI - Propranolol in the treatment of acute migraine attacks. AB - The efficacy of the beta-adrenoceptor antagonist propranolol in the acute treatment of patients in attacks of either classical (migraine with aura) or common migraine (migraine without aura) headache was assessed in a double-blind placebo-controlled crossover trial with fixed doses. The trial was carried out on 25 patients. The treatment period was set at eight weeks, with the provision of shortening or lengthening it if necessary with a maximum period of seventeen weeks. A minimum of three migraine attacks were treated during each treatment period. Patients were assessed according to: the mean duration and mean severity per treatment period of migraine attacks. The secondary efficacy assessment was made on the basis of the percentage of attacks requiring escape medication per treatment period. The study, based on the t-distribution statistical model with a confidence level of 95%, showed that propranolol had no significant effect in aborting acute attacks of migraine when compared with placebo. PMID- 1742776 TI - A note on the action of glutamine on cortical spreading depression. AB - Application of a solution of 1-glutamine, 75 mM, to the pia-arachnoid surface of the dorsolateral neocortex of rabbits under dial-urethane anaesthesia was found to reversibly render the tissue insusceptible to spreading depression. It is suggested that this amide may play a part in the opposition normally offered by the tissue to undergo spreading depression. Some evidence is adduced which seems to support this suggestion. PMID- 1742777 TI - Double wire technique for additional guiding catheter support in anomalous left circumflex coronary artery angioplasty. AB - This case report presents an example of the use of the double wire technique for additional guiding catheter bracing support in percutaneous transluminal coronary angioplasty (PTCA) of a stenosis in an anomalous circumflex (CX) artery arising within the ostium of the right coronary artery (RCA). It illustrates the ease of this technique in comparison to conventional guiding catheter cannulation, which may be more difficult and yield poor backup support in this unusual anatomic situation. PMID- 1742778 TI - Two hugging balloons at high pressures successfully dilate a lesion refractory to routine coronary angioplasty. AB - A small portion of lesions are refractory to coronary angioplasty even when very high pressures are used. This leads to a failed angioplasty and emergent bypass surgery. We successfully attempted the technique of hugging balloons or two polyethelene terephthalate (PET) balloons inflated simultaneously side by side which successfully dilated a lesion which would not dilate using standard techniques. This technique successfully dilated the lesion as the geometry of two balloons inflated side by side is different from one balloon. Two balloons inflated side by side consists of two outer semi-circles and a central trapezoidal square area. This altered geometric configuration may be important in successfully dilating a lesion refractory to standard dilating techniques. Higher pressures can be attained with smaller balloons as the burst pressure is higher in smaller balloons compared to larger balloons. PMID- 1742779 TI - Coronary artery to middle cardiac vein fistula following endomyocardial biopsy in a heart transplant patient. AB - Coronary artery fistulas draining directly into the right ventricle have been recognised as a complication of transvenous endomyocardial biopsy procedures performed in heart transplant recipients. We report a case where a fistula drained into the middle cardiac vein and outline the possible mechanism of occurrence and its prevention. The diagnostic and therapeutic aspects of these "acquired" fistulas are reviewed. PMID- 1742780 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: percutaneous balloon valvuloplasty. AB - The hemodynamic findings of aortic, mitral and pulmonary balloon valvuloplasty serve to identify classical valvular lesions and their responses to graded or abrupt catheter dilation techniques. The production of mild insufficiency after valve dilation is generally well tolerated. Severe valvular insufficiency produces the expected hemodynamic alterations, but acute decompensation may be witnessed over brief periods of time. The use of extra stiff guidewires across dilated valves, especially the aortic valve, may also produce an exaggerated hemodynamic picture of insufficiency. Although gradients may be reduced, the effect of valve dilation on aortic valve area is generally small. A discussion of factors influencing valve area calculations will be the subject of a future "Rounds." PMID- 1742781 TI - Coronary artery quantitation and data management system for paired cineangiograms. AB - A computerized system designed to optimize the quantitation of coronary vessels on 35 mm cineangiograms is described and validated. Because the system has two cine film digitizers, it processes paired coronary arteriograms for the evaluation of serial changes in coronary arteries. A database system was specifically designed for the storage of coronary artery quantitation data which resides on a file server in a local area network and may be accessed by multiple workstations. In radiographic phantom studies of nine contrast-filled lucite cylinders of known size, the overall accuracy and precision for the measured diameters were 0.069 mm and 0.066 mm respectively. Measurements of minimum diameter and percent diameter stenosis of 21 coronary lesions selected from 17 routine cineangiograms showed high degree of intraobserver and interobserver reproducibility. PMID- 1742782 TI - Method to allow safe catheterization of extremely obese patients. PMID- 1742783 TI - Initial experiences with a miniaturized pressure transducer during coronary angioplasty. AB - A newly constructed pressure sensor with a diameter of 0.45 mm was evaluated in 15 patients undergoing balloon coronary angioplasty (PTCA). The sensor and an optic fiber were mounted on a 0.018" guide wire, which was used in the balloon catheter. Pressure gradients were recorded before and after PTCA, respectively. The pressure tracings were of satisfactory quality in all cases. The mean systolic and diastolic gradients before PTCA were 32 +/- 20mm Hg and 44 +/- 26mm Hg, respectively. Pressure gradients were also obtained with the balloon placed in the lesion in order to simulate the conventional way of pressure measurement through the balloon catheter. In this setting, the systolic and diastolic gradients were 77 +/- 32mm Hg and 59 +/- 25mm Hg, respectively. Following balloon dilatation, the systolic pressure gradient decreased to 14 +/- 12mm Hg, and the diastolic gradient to 13 +/- 11mm Hg. In conclusion, this new pressure sensor delivers recordings of good quality and may be especially of interest during angioplasty due to its small diameter. PMID- 1742784 TI - Performance characteristics of a new shape of guiding catheter for PTCA of the left coronary artery. AB - The inability to successfully perform angioplasty commonly involves inadequate guiding catheter performance. We evaluated the use of a new left coronary guiding catheter for angioplasty (PTCA) of lesions in both the left anterior descending and left circumflex arteries. The Nesto guide in two different sizes was used in 100 consecutive PTCA cases as a primary catheter. The catheter successfully cannulated the left main coronary artery in 93 patients and PTCA was successfully performed in 85 patients for target lesions at various locations in either or both vessels. Positive features of this new guiding catheter include superior back-up support and ease of disengagement. PMID- 1742785 TI - Coronary artery to left ventricular fistula. PMID- 1742786 TI - Right heart catheterization. PMID- 1742787 TI - Selective thrombolysis with rt-PA: a promising approach for the management of embolic cerebrovascular complications during left heart catheterization? PMID- 1742788 TI - Cardiac catheterization 1990: a report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I). AB - This report presents the first year's experience of a totally computerized cardiac catheterization laboratory reporting system, including the results and complications of invasive and interventional procedures. Sixty-three laboratories reported a total of 71,916 patients studied between January 1 through December 31, 1990. Two previous registry reports have been published. Compared with data acquired by previous methods, in spite of an older and sicker population, the mortality for diagnostic procedures has remained remarkably constant (0.11%). The computerized format facilitates data collection and analysis, helps resolve new issues as they arise and serves as a method of monitoring quality of laboratories and individuals. PMID- 1742789 TI - Predictors of early mortality in patients with angiographically documented left main coronary artery disease. AB - To determine predictors of early death after coronary angiography in patients with significant left main coronary artery disease (greater than or equal to 60% diameter narrowing, LMCAD), we reviewed the clinical records of patients with LMCAD who died after angiography. Of 1,288 patients with LMCAD studied between January 1978 and October 1989, 21 died within 2 days after angiography (group 1). As a control group, 85 patients were randomly sampled from 1,196 patients who survived at least 30 days after angiography (group 2). The predictors of early death after angiography in patients with LMCAD were older age (P less than 0.05), New York Heart Association Class III or IV (P less than 0.005), shorter duration of unstable angina (P less than 0.005), higher left ventricular end-diastolic pressure (P less than 0.006), lower ejection fraction (P less than 0.005), and significant left circumflex artery disease (P less than 0.006). The use of heparin infusion after angiography did not appear to be a significant factor. It is suggested that earlier operation or more aggressive management be undertaken in patients who, at cardiac catheterization, have significant LMCAD associated with the above-listed variables. PMID- 1742790 TI - Angioplasty in ulcerative coronary artery disease: acute results and early follow up. AB - The safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA) for stenoses involving ulcerative lesions were retrospectively studied. Seventy seven patients (62 men and 15 women, mean age 62 +/- 10 years) representing 3.4% of 2,250 patients treated with PTCA during the period January 1, 1988 and June 30, 1990, had pre-PTCA stenoses defined as ulcerated. Twenty-eight (36%) of the stenoses were localized in the left anterior descending coronary artery, 9 (12%) in the left circumflex and 40 (52%) in the right coronary artery. During angioplasty, percent diameter stenosis was reduced from 73 +/- 14% to 22 +/- 13% and transstenotic gradient decreased from 48 +/- 18 to 12 +/- 6 mm Hg. Clinical success (freedom from angina at discharge without coronary bypass surgery, infarction or death) was achieved in 70 patients (90.9%). There were seven unsuccessful cases: three underwent elective coronary bypass surgery, one was managed medically, and three developed a major flow interrupting dissection during the procedure requiring emergency coronary bypass surgery. There were no deaths. At mean follow-up of 7.6 months, 45 of 61 patients (73.7%) remained asymptomatic. One patient needed an elective coronary bypass surgery and five patients had a successful repeat PTCA. In conclusion, PTCA for an ulcerated stenosis can be performed safely with a high primary success rate and a favorable early clinical course. PMID- 1742791 TI - Effect of drugs on a noninvasive index of arterial compliance in healthy and heart failure patients. AB - Ten healthy (aged 28 to 39) and ten heart failure NYHA II (aged 19 to 49) male subjects were prospectively studied under no drugs, under furosemide (40 mg/day), under captopril (150 mg/day) and under their association. Arterial compliance (ml/mmHg) was measured in all subjects at rest and supine. Heart failure etiology was dilated cardiomyopathy or ischemic heart disease without significant regurgitation. Arterial compliance was significantly higher in healthy than in heart failure patients in all studied conditions (p less than 0.001) (healthy = 2.2 + 0.29 vs. heart failure = 0.79 + 0.14). Neither single drug nor their association induced any change in healthy subjects. Arterial compliance progressively increased in heart failure with furosemide, captopril, and their association (no drug = 0.79 + 0.14; furosemide = 0.87 + 0.15; captopril = 0.94 + 0.15 and furosemide + captopril = 0.99 + 0.14). Captopril induced a higher increment than furosemide (p less than 0.001) and their association even a higher increment (p less than 0.001) than any single drug. Thus captopril and/or furosemide increased arterial compliance in heart failure but not in healthy subjects, possibly through changes in arterial wall edema and smooth muscle contraction. PMID- 1742792 TI - Combined intravascular ultrasound/angioplasty balloon catheter: initial use during PTCA. PMID- 1742793 TI - Production of glycosaminoglycans by human skin fibroblasts growing in a collagen lattice. AB - Production of glycosaminoglycans (GAG) by human skin fibroblasts cultured in collagen lattices closely resembled that already described for the same cells grown as monolayers on plastic. There was no inhibition of GAG corresponding to that of DNA and protein synthesis and similar controls by cell density and anti inflammatory drugs operated in 3-dimensional as in 2-dimensional culture. The bulk of the GAG synthesised in lattice culture was hyaluronic acid, as in monolayers. PMID- 1742794 TI - Effect of vasopressin and protein kinase C inhibitors on junctional conductance in isolated heart cell pairs. AB - The effect of vasopressin on junctional conductance (gj) in isolated heart cell pairs was investigated. The results indicated that vasopressin (60 nM) causes a decrease in gj of 53% (S.E. +/- 5) (n = 10) within 15 sec. of its administration to the bath. The effect of vasopressin was dose-dependent and was suppressed by staurosporine (50 microM)--a potent inhibitor of protein kinase C. Inhibitors of protein kinase C by themselves increased gj. The results indicate that protein kinase C plays an important role in the control of gj in heart muscle. PMID- 1742795 TI - Toxicity of gentamicin in organ culture of fetal rat intestine. AB - The effect of gentamicin in the culture of fetal rat intestine was studied. Fetal rat intestine was cultured with gentamicin or kanamycin at the concentration between 4 to 200 micrograms/ml. Kanamycin did not have influence on lactase, maltase and ALP activities. On the other hand, gentamicin caused decrease of lactase and ALP activities at the concentration of 40 and 200 micrograms/ml compared with the activities at 4 micrograms/ml. Maltase activities did not decrease with gentamicin. Our data suggest that gentamicin could affect lactase and ALP activities and lower concentration should be used in the culture. PMID- 1742796 TI - Increased release of von Willebrand factor antigen by endothelial cells whilst in active growth phase. AB - Human umbilical vein endothelial cells and fibroblasts were grown in tissue culture (with and without added endothelial cell growth supplement) to confluence. von Willebrand factor antigen was measured in supernatants every 24 hours. Cells grown in medium with growth supplement reached confluence before those grown without the supplement. von Willebrand factor antigen release was greatest under both sets of conditions when cells were in their most active growth phase, and rate of release slowed when cells were confluent. Fibroblasts grew more rapidly, showed a small response to the growth supplement, but supernatant von Willebrand factor antigen could not be detected. The implications of these findings for atherogenesis are discussed. PMID- 1742798 TI - Effect of nerve growth factor on lesioned PC12 cells. AB - The protecting effect of nerve growth factor (NGF) from hydrogen peroxide was studied on PC12 cells conditioned at 1 mM hydrogen peroxide with NGF and without NGF in comparison with cells treated with neither hydrogen peroxide nor NGF. NGF treatment of PC12 cells increased significantly the activity of catalase representing induction of free radical detoxifying mechanisms. The protection effect of NGF was reflected also on enhanced activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the cells. PMID- 1742797 TI - Expression of laminin by human fibroblasts, HT1080 fibrosarcoma cells and MCF-7 breast adenocarcinoma cells. Lack of regulation by the cell density and extracellular matrix. AB - We have cultured normal fibroblasts, fibrosarcoma HT1080 cells and breast adenocarcinoma MCF-7 cells on various substrates (plastic, collagen type I, laminin). All cell types used adhered on the three substrates with, however, a delayed attachment on laminin. On all substrates, cell grew as monolayer with the exception of MCF-7 cells that formed clusters on laminin. The epithelial MCF-7 cells as well as mesenchymal cells (fibroblasts and tumoral HT1080 cells) synthesized laminin and expressed mRNA coding for laminin B1 chain and for the 67 kD laminin binding protein. The levels of these mRNAs were not modulated by culture conditions which affect cell morphology nor by cell density. PMID- 1742799 TI - Intracellular calcium of longitudinal muscles isolated from pregnant rat myometrium. AB - Longitudinal muscle cells were successfully isolated from pregnant rat myometrium (21 days of gestation) with more than a 95% survival rate. The approximate size of relaxed cells was 232.2 +/- 74 microns in length and 16.2 +/- 7.0 microns in width. Using the fluorescent indicator Fura-2, the concentration of intracellular free calcium ([Ca2+]i) in resting state cells was calculated to be 116 +/- 18.5 nM. The isolated cells responded well to K+, acetylcholine and oxytocin in terms of contraction as well as the increase in [Ca2+]i. The increase in [Ca2+]i induced by acetylcholine and K+ appeared to be mainly due to an influx of extracellular Ca2+. On the other hand, the oxytocin-induced increase in [Ca2+]i was mainly due to a release of Ca2+ from intracellular storage sites in the isolated cells. Isolated longitudinal muscle cells can serve as a useful tool in establishing the relationship between [Ca2+]i and regulation of the uterine contraction at the final stage of pregnancy. PMID- 1742801 TI - Changes in tissue fibronectin in elastase induced lung injury. AB - We studied changes in rat lung fibronectin (FN) content and synthesis after endobronchial administration of elastase. A severe hemorrhagic neutrophilic alveolitis ensued with plasma protein leakage, initial rise in tissue FN content, and sustained rise in FN synthesis. Unlike fibrotic models where initial rises in tissue FN levels are sustained, levels in this model normalized promptly. This, in the setting of increased synthesis is consistent with increased degradation. This degradation of tissue FN may result in the disruption of the lung architecture, interfere with the deposition of newly synthesized matrix and could partly explain the development of emphysema in a model where excess fibronectin synthesis is observed. PMID- 1742800 TI - Ultrastructural localization of the nuclear protein mitotin during the cell cycle. AB - The work presents the results of the immunoelectron microscopical localization of mitotin in different phases of the cell cycle. The distribution of the protein was studied using its specific monoclonal antibody and immunogold labeling in synchronized WISH cells. In S phase the antigen was found in the nucleoplasm usually over the interchromatin granules. In G2 phase the amount of mitotin increases and it can be found also in the nucleolus. In mitosis the immunogold granules are always out of the condensed chromosomes. PMID- 1742802 TI - Ultrastructural localization of dystrophin in chicken smooth muscle. AB - We investigated the presence of dystrophin in gizzard smooth muscle by immunofluorescence assay, immunoblot detection and an immunogold electron microscopy technique. Western blot analyses, using antibodies raised against sequences 1173-1728 and 3357-3660 of the dystrophin molecule, revealed the presence of a major intact 400 kDa protein band and an immunofluorescence localization restricted to the periphery of the smooth muscle cells. We were able to precisely determine the dystrophin distribution along the plasmalemma whereas caldesmon molecules were present in the cytoplasm. The most commonly observed distance between two neighbouring dystrophin molecules suggested a self associating arrangement. We discuss these findings in relation to the function of dystrophin in the smooth muscle cell structure. PMID- 1742803 TI - Human leucocyte migration through collagen matrices containing other extracellular matrix components. AB - The purpose of this study was to investigate the migration of human peripheral blood leucocytes through collagen gels containing extracellular matrix components in vitro. This further extends the findings of a previous study (Reid et al, 1990), using rabbit peritoneal neutrophils, in which it was found that increasing the mechanical strength of the gels decreased the cell migration. In the current study it was found that human neutrophil and lymphocyte migration through collagen matrices was inhibited by increasing the collagen concentration, whereas the presence of serum had no effect on migration. Incorporation of chondroitin sulphate into collagen gel matrices resulted in a slight increase in leucocyte migration. The presence of elastin had no effect on the migration of leucocytes through collagen matrices, whereas incorporation of hyaluronate into collagen matrices decreased leucocyte migration. The morphology of these matrices suggests that altered migration was not due to differences in pore size between fibres. PMID- 1742804 TI - Differential effects of concanavalin A, serum and cytokines on proteoglycan elaboration and DNA synthesis by mononuclear cells from human peripheral blood. AB - Human blood derived mononuclear cell (MC) cultures required concanavalin A (Con A) stimulation to synthesize and secrete into the medium high levels of a protease-resistant proteoglycan (PG) containing predominantly chondroitin sulfate (CS), which was elaborated largely by T-cells in culture. PG and DNA synthesis were studied in MC cultures in the absence and presence of Con A as well as serum and some biologically active polypeptide factors. In the presence of Con A, stimulation of PG synthesis was substantially greater in T-cell enriched cultures than in B-cell enriched cultures. DNA synthesis was also stimulated in the presence of Con A. This stimulation was concentration-dependent, but required the presence of serum for additional responses. DNA and cell proliferation were stimulated by interleukin-2 (IL-2), but PG production was not stimulated by conditioned media, IL-1, IL-2, IL-3, or transforming growth factor-beta (TGF beta). Our results indicate that the elaboration of PG from T-cells of human MC is independent of the effects of regulatory peptides on cell proliferation and DNA synthesis. PMID- 1742805 TI - Hepatitis A outbreak in Grand Forks, British Columbia, 1990. PMID- 1742806 TI - Three dimensional structure of GD1b and GD1b-monolactone gangliosides in dimethylsulphoxide: a nuclear Overhauser effect investigation supported by molecular dynamics calculations. AB - A comparative study on the conformational features of the oligosaccharide moiety of GD1b and GD1b lactone gangliosides, in dimethylsulphoxide, has been carried out by nuclear Overhauser effect investigation; the experimental interresidue contacts have been used for restrained molecular mechanics and dynamics calculations. For GD1b, the tetrasaccharide beta-GalNAc-(1----4)-[alpha-Neu5Ac-(2 ----8)-alpha-Neu5Ac-(2----3)]-beta-Gal has a circular arrangement leaving a highly hydrophobic region with seven hydrogens pointing towards the center. At one side of this region the three electron rich groups GalNAc--NH, external Neu5Ac--OH4 and internal Neu5Ac--COO- are grouped together; at the other side five polar groups (four hydroxy groups and the external Neu5Ac carboxylate) define a large annular hydrophilic region. The external Neu5Ac is close to the external Gal residue, and the external Neu5Ac--COO- is within van der Waals contact with the inner Neu5Ac-OH9 group. The beta-Gal-(1----3)-beta-GalNAc glycosidic linkage shows a high degree of freedom. For GD1b-L, the trisaccharide beta-GalNAc-(1----4)-[alpha-Neu5Ac-(2----3)]-beta-Gal is disposed to forming rigid partially circular arrangement showing strong interresidue contacts between the inner Neu5Ac-H8 and both GalNAc-H1 and GalNAc-H5. The conformation of the lactone ring is the boat 9(A),2(B)B. The lactonization of the disialosyl residue induces a strong variation of the preexisting torsional glycosidic angles phi and psi, leaving the external Neu5Ac far from the external Gal. In both GD1b and GD1b lactone gangliosides, the conformation of the sialic acid side chain is the same as that of the free sialic acid in which the H7 is trans to H8 and gauche to H6, thus indicating that the presence of glycosidic and/or ester linkages does not affect the conformational properties of sialic acid. Both GD1b and GD1b lactone containing sialic acid carboxylate anion(s) or undissociated carboxyl group(s) show the same three dimensional structure, indicating that the presence of charges does not affect the intrinsic conformational features of gangliosides. PMID- 1742807 TI - Incorporation of phosphonic acid diesters into lipid model membranes. Part II. X ray and neutron diffraction studies. AB - Mixtures of egg phosphatidylcholine and phosphonic acid diethyl or dibutyl esters of the general type RP(O)(OR')2 with R = hexane or dodecane were studied at room temperature in the fluid lamellar state by X-ray and by neutron diffraction. Generally a molar ratio of lipid and ester of 1:0.5 was used. Additionally an equimolar lipid/ester mixture of hexane phosphonic acid diethyl ester was studied. Depending on the ester used and its concentration a single L alpha-phase was observed above a certain water content which changes to an L alpha + water two phase system at high water concentration. Despite the large amounts of the amphiphilic ester molecules incorporated in the membrane and their high molecular asymmetry, the mixtures qualitatively show the typical hydration and swelling behaviour of non-charged lipid membranes. However, the incorporation of the esters induces a higher hydration capacity, a lateral extension and a decrease in membrane thickness. The position of the ester molecules and their orientation in the membrane were determined by neutron diffraction using partially deuterated esters. The esters were found to be located with their phosphonic moiety near or in the lipid/water interface. The lamellar structure contradicts this location of the cone-shaped ester molecules which should increase the tendency to form hexagonal structures. However, the experimental findings can be understood if one considers a partial interdigitation of the last hydrocarbon groups of the lipid chains accompanied by a larger disorder in the hydrophobic centre of the membrane. In the case of hexane phosphonic acid dibutyl ester, a vertical translocation of the ester takes place below a certain water content where it is distributed between two locations at the lipid water interface and the centre of the membrane. PMID- 1742808 TI - A structural study of interfacial phospholipid and lung surfactant layers by transmission electron microscopy after Blodgett sampling: influence of surface pressure and temperature. AB - Monolayer studies of the lung surfactant extract (LSE), dipalmitoyl phosphatidilcholine (DPPC) and dioleyl phosphatidilcholine (DOPC) have been performed in the dynamic condition at various temperatures. These compounds were also studied by differential scanning calorimetry, and the Langmuir Blodgett films were examined by electron microscopy. The combination of these techniques allowed us to describe precisely the collapse process, which was found to be different above and below the transition temperature of the lipids. However, whereas a phase separation for DPPC/DOPC mixtures occurred at all temperatures studied, this separation was observed for LSE only at temperatures lower than that characteristic of the "rigid state" to "liquid-like state" transition temperature. The ability of LSE to rapidly respread upon decompression appears to be due to the formation of piled amorphous aggregates formed during compression of its monolayers. PMID- 1742809 TI - Aggregation behavior of lipid IVA in aqueous solutions at physiological pH. 1: Simple buffer solutions. AB - We have investigated the aggregation behaviour of lipid IVA (a bioactive precursor of lipid A and the lipid anchor of lipopolysaccharide) in aqueous solutions in the physiological pH range using dynamic light scattering, nuclear magnetic resonance, fluorescence, surface pressure, electron microscopy and force field simulation studies. The sonication of lipid IVA in PBS, Tris and Hepes produces vesicles which are stable in the concentration range of 10(-3) - 10(-7) M, possibly even at lower concentrations. The vesicle size is not sensitive to the nature of the buffer, only to the pH and to some extent to the ionic strength. The long time stability of the small unilamellar vesicles as well as the structureless 1H-NMR spectra might be attributed to a rigid surface structure. This structure is also supported by the simulation studies. We have tentatively proposed a coexistence of micelles and/or other aggregates with the bilayered vesicles at higher lipid concentrations in order to explain some of the experimental observations. PMID- 1742810 TI - Membrane specificity of non-monotonic trends in cation-mediated injury to rapidly frozen phospholipid vesicles. AB - Phospholipid vesicles like erythrocyte ghosts [1] have been shown to display trends in freeze-thaw injury with Group I ions which are non-monotonic in nature. That is to say, the relative extent of injury with such ions, measured as calcein release, does not follow a lyotropic series related solely to the hydrated ionic radii of these ions. By incorporation of cholesterol into the vesicles the non monotonic nature of these trends has been shown to be highly membrane specific. Thus the non-monotonic trends in cation mediated freeze-thaw injury are shown to be independent of bulk solution properties. PMID- 1742811 TI - Effect of the fungicides tributyltin acetate and tributyltin chloride on multilamellar liposomes: fluorescence studies. AB - The influence of tri-n-butyltin acetate (TBTA) and tri-n-butyltin chloride (TBTC) on the physico-chemical state of charged and neutral phospholipids was investigated using multilamellar liposomes. The thermal dependence of steady state fluorescence polarization of DPH and its charged derivative TMA-DPH was recorded. The two fungicides lowered DPPC phase transition temperature and broadened the temperature range of the transition in different ways. The effects were concentration-dependent. The results show that TBTC interacts more effectively with DPPC model membranes rather than TBTA. Moreover, TBTC broadens and shifts the main phase transition (Tm) more effectively in DPPC rather than in DMPC liposomes. Below Tm, TBTC decreases fluorescence polarization (P) in all phospholipids used. Above Tm P is almost constant in phospholipids with saturated acyl chains, except for DMPG. In fact, an increase of P is detectable in this lipid as in PLs with unsaturated acyl chains. It is suggested that the effects of TBT on liposomal membranes are dependent on the anion moiety and phospholipids characteristics. PMID- 1742812 TI - Noninvasive measurement of cerebral blood flow: techniques and limitations. PMID- 1742813 TI - Obstetric anaesthesia in patients with primary pulmonary hypertension. PMID- 1742815 TI - Concurrent increases in brain electrical activity and intracranial blood flow velocity during low-dose ketamine anaesthesia. AB - The purpose of the present study was to assess the effects of low-dose ketamine on spontaneous brain electrical activity (EEG) and intracranial blood flow velocity. Twenty healthy volunteers were divided into two groups: Group I (n = 10) received 0.25 mg.kg-1 ketamine iv; Group II (n = 10) received 0.5 mg.kg-1 ketamine iv. Mean arterial blood pressure (MAP), heart rate (HR), end-tidal PCO2 (PETCO2), and arterial oxygen saturation (SaO2) were measured. The EEG was recorded from temporo-occipital recording sites over both hemispheres. Blood flow velocity in the middle cerebral artery was measured using a transcranial Doppler ultrasound system. All variables were evaluated at baseline and for 60 min following ketamine. Administration of ketamine resulted in increases of MAP and HR in both groups to a similar degree. The PETCO2 and SaO2 did not change in either group over time. Ketamine caused a dose-dependent, transient shift in the EEG to synchronous high-voltage slow waves with an increase in total power (Group I: 301 +/- 38%; Group II: 104 +/- 28%). These changes were associated with dose dependent increases in mean blood flow velocity (Group I: 35 +/- 7%; Group II: 68 +/- 10%). Our data suggest that increases in intracranial blood flow velocity are closely correlated to increases in neuronal activity and are not secondary to changes in systemic haemodynamic variables. PMID- 1742814 TI - Cerebrovascular responses to carbon dioxide in children anaesthetized with halothane and isoflurane. AB - To determine the effects of isoflurane and halothane on cerebrovascular reactivity to CO2, 30 children aged one to six years were anaesthetized with isoflurane or halothane in an air and oxygen mixture with an FIO2 of 0.3. The end tidal concentrations (0.5 minimum alveolar concentration (MAC) or 1.0 MAC) of isoflurane or halothane were age-adjusted. After achieving a steady-state at both 0.5 MAC and 1.0 MAC isoflurane and halothane, the end-tidal carbon dioxide tension (PETCO2) was randomly adjusted to 20, 40, or 60 mmHg. Cerebral blood flow velocity (CBFV) and the cerebrovascular resistance index (RI+) in the middle cerebral artery (MCA) were measured by a transcranial Doppler monitor. Three measurements of CBFV and RI+ were obtained at each PETCO2 and isoflurane or halothane concentration. Any rise in the PETCO2 caused an increase in CBFV during both 0.5 MAC (r2 = 0.99 and 0.99) and 1.0 MAC (r2 = 0.96 and 0.95) isoflurane and halothane anaesthesia, respectively (P less than 0.05). The CBFV for isoflurane increased as PETCO2 increased from 20 to 60 mmHg for both 0.5 MAC and 1.0 MAC (P less than 0.05). The CBFV for halothane increased as PETCO2 increased from 20 to 40 mmHg for both 0.5 MAC and 1.0 MAC halothane (P less than 0.05), but did not change as PETCO2 increased from 40 to 60 mmHg for both 0.5 MAC and 1.0 MAC halothane. The RI+ showed an inverse relationship with CBFV at each PETCO2 for 0.5 MAC (r2 = 0.98 and 0.99) and 1.0 MAC (r2 = 0.76 and 0.53) isoflurane and halothane, respectively (P less than 0.05). The CBFV did not differ significantly between 0.5 and 1.0 MAC isoflurane and halothane at corresponding PETCO2 values. The cerebrovascular response to CO2 at 20 mmHg between 0.5 MAC and 1.0 MAC halothane was not significantly different. These data strongly suggest that isoflurane and halothane in doses up to 1.0 MAC do not affect the cerebrovascular reactivity of the MCA to CO2 in anaesthetized, healthy children. PMID- 1742816 TI - Local cerebral blood flow with prostaglandin E1 or trimethaphan during cerebral aneurysm clip ligation. AB - This study was performed to examine changes in local cerebral blood flow during hypotensive anaesthesia with either prostaglandin E1 (PGE1) or trimethaphan (TMP). Local cerebral blood flow (LCBF), mean blood pressure (MBP), heart rate (HR), and hourly urine output (UO) were studied in 51 patients undergoing cerebral aneurysm surgery with neuroleptanalgesia (NLA). The incidence of vasospasm after aneurysm surgery, and outcome (Glasgow Outcome Scale) at discharge were evaluated. Measurements of LCBF were made using a thermal gradient blood flow meter. The dose of PGE1 or TMP was adjusted to maintain MBP at about 70 mmHg, and LCBF was studied during and after PGE1 or TMP administration. Hypotensive drugs were discontinued at the completion of aneurysm clipping. After starting PGE1 or TMP, MBP decreased immediately, but HR did not change in either group. The LCBF decreased 30 min after the start of TMP administration and increased immediately after its discontinuation, whereas PGE1 did not affect LCBF. Urine output increased during PGE1 administration but was unchanged during TMP. Neither drug affected surgical outcome or the incidence of vasospasm. These results suggest that PGE1 may be preferable to trimethaphan for hypotensive anaesthesia in cerebral aneurysm surgery because LCBF is maintained. PMID- 1742818 TI - Haemodynamic response to induction of anaesthesia with ketamine/midazolam. AB - The haemodynamic responses following induction of anaesthesia with ketamine and midazolam have not been determined previously. Twenty adult patients for elective myocardial revascularization were randomized to two regimens for induction of anaesthesia. Patients in Group I received ketamine, 2 mg.kg-1, and midazolam, 0.2 mg.kg-1 and those in Group II received ketamine, 2 mg.kg-1, and midazolam, 0.4 mg.kg-1. Measurements were recorded at baseline, 1 min post-induction, and at one, three, five and ten minutes after tracheal intubation. Tachycardia and hypertension (greater than 20% increases from awake baseline values) were treated with esmolol, 250 micrograms.kg-1. There were 11 patients in Group I and nine patients in Group II. There were no significant intergroup differences in demographic or haemodynamic variables. Both groups had decreases (P less than 0.05), in stroke volume, pulmonary capillary wedge pressure, and right ventricular end-diastolic volume at multiple study intervals following anaesthetic induction. None of these changes required clinical intervention. Five patients (all in Group II) had hypertensive responses to tracheal intubation. Preoperative hypertension (mean arterial pressure greater than or equal to 100 mmHg) was a predictor (P less than 0.05) of a hypertensive response to intubation, independent of the midazolam dose. Intravenous ketamine and midazolam was associated with a high incidence (25%) of haemodynamic responses to tracheal intubation. The higher dose of midazolam did not provide any haemodynamic advantage. PMID- 1742817 TI - Cardiovascular and endocrine effects of clonidine premedication in neurosurgical patients. AB - The present study was conducted to examine the haemodynamic and endocrine effects of clonidine, given as sole preanaesthetic medication, in neurosurgical patients. Nineteen patients of ASA physical status I and II, subjected to craniotomy, randomly received po premedication of either clonidine (300 micrograms, n = 9) or placebo (n = 10). Blood pressure and heart rate were monitored continuously, while arterial blood samples were collected at specific times, from induction of anaesthesia to recovery, for the measurement of plasma concentrations of epinephrine, norepinephrine, cortisol, aldosterone, and glucose. Clonidine treatment led to a decrease in mean arterial blood pressure (MABP), heart rate (HR), and plasma cortisol and aldosterone concentrations throughout the study, compared with placebo (P less than 0.05). Clonidine, however, did not prevent increases in MABP (16 +/- 5 mmHg, mean +/- SE, P less than 0.05) and HR (18 +/- 4 bpm, P less than 0.05) during induction of anaesthesia, which was comparable to the placebo group. Plasma catecholamine concentrations did not differ between the two groups. Plasma glucose concentrations increased in both groups at the end of the study (P less than 0.05), but were lower in clonidine-treated patients (P less than 0.05). Though statistically significant, the observed inhibitory haemodynamic and endocrine effects of clonidine seem to be of minor clinical importance. As the action of clonidine on cerebral blood flow regulation is not well known, we see no advantage in the preanaesthetic administration of clonidine to neurosurgical patients with normal cardiovascular status. PMID- 1742819 TI - Stability of the intraoperative arterial to end-tidal carbon dioxide partial pressure difference in children with congenital heart disease. AB - The purpose of this study was to evaluate the stability of the arterial PCO2 (PaCO2) to end-tidal PCO2 (PETCO2) partial pressure difference (Pa-ETCO2) during surgery using PETCO2 monitoring, in children with congenital heart disease (CHD). Forty children with CHD were studied: ten children with no interchamber communication and normal pulmonary blood flow (PBF) (normal group); ten acyanotic children with increased PBF (acyanotic-shunting group); ten cyanotic children with mixing type lesions and normal or increased PBF (mixing group), and ten cyanotic children with right-to-left intracardiac shunts demonstrating decreased and variable PBF (cyanotic-shunting group). Simultaneous PaCO2 recordings and PETCO2 measurements were obtained for each patient during five intraoperative events: (1) control time, arterial line placement under anaesthesia; (2) time 1, patient preparation; (3) time 2, immediately after sternotomy; (4) time 3, after heparin administration; and (5) time 4, immediately after aortic cannulation. Initially, cyanotic children demonstrated a greater Pa-ETCO2 compared with acyanotic children (P less than 0.05). There was no difference in the Pa-ETCO2 over time in the control, acyanotic-shunting, or mixing groups. The Pa-ETCO2 in the children with cyanotic-shunting lesions at times 2 and 3 was greater (P less than 0.05) than at their control times. We conclude that the Pa-ETCO2 of children with acyanotic-shunting and mixing congenital heart lesions is stable intraoperatively, although patients with mixing congenital heart lesions may demonstrate large individual variations. In children with cyanotic-shunting congenital heart lesions, the Pa-ETCO2 is not stable. The PETCO2 cannot be used during surgery to estimate reliably the PaCO2 in children with cyanotic CHD. PMID- 1742821 TI - Day surgical anaesthesia: which patients? Which procedures? PMID- 1742822 TI - Outpatient anesthesia. Which is the best anaesthetic technique? PMID- 1742820 TI - Brachial plexus block with bupivacaine: effects of added alpha-adrenergic agonists: comparison between clonidine and epinephrine. AB - The effects of clonidine and epinephrine, administered into the brachial plexus sheath, were evaluated in 60 patients who underwent surgery of the upper limb. All patients received 40 to 50 ml of 0.25% bupivacaine, injected into the brachial plexus sheath, using the supraclavicular technique. The patients were randomly allocated to two groups so that 30 patients received 150 micrograms clonidine hydrochloride (Group I), and 30 received 200 micrograms epinephrine (Group II). The quality and the duration of analgesia were assessed as well as the possible side-effects. The block produced with the addition of clonidine was longer (994.2 +/- 34.2 vs 728.3 +/- 35.8 min) and superior to that with epinephrine (P less than 0.001). No major side-effects were recorded. We conclude that the injection of clonidine into the brachial plexus sheath is an attractive alternative to epinephrine to prolong the duration of analgesia following upper limb surgery under conduction anaesthesia. PMID- 1742823 TI - Selection of patients for paediatric ambulatory surgery. PMID- 1742824 TI - Outpatient anesthesia. What are the problems in the recovery room? PMID- 1742825 TI - Pulmonary hypertension and cardiomyopathy: anaesthetic management for caesarean section. AB - Pulmonary hypertension in pregnant women is uncommon but is associated with a high mortality. We present the case of a 14-yr-old parturient with pulmonary hypertension and cardiomyopathy who required a Caesarean section. Management goals included: (1) maintaining right ventricular function, (2) avoiding the haemodynamic effects of general endotracheal anaesthesia, and (3) minimizing narcotic-related neonatal respiratory depression. While most authors agree on invasive pulmonary and systemic monitoring, opinions differ as to the optimal method of providing anaesthesia for these patients. The successful use of lumbar epidural anaesthesia with lidocaine and fentanyl is described. When the local anaesthetic was administered slowly and in increments, epidural anaesthesia was safe for both mother and fetus. PMID- 1742826 TI - Anaesthetic management of a complex morbidly obese parturient. AB - A case is presented of a morbidly obese parturient who had multiple medical problems. She had angina and was receiving nitrate therapy, had insulin-dependent diabetes mellitus, hypertension, asthma and benign intracranial hypertension (pseudotumour cerebri). Lumbar epidural analgesia was chosen for labour and delivery and resulted in an uneventful outcome. PMID- 1742827 TI - Anaesthesia for caesarean section in a patient with acute fatty liver of pregnancy. AB - A 23-yr-old woman presented in labour and hepatic failure. The clinical diagnosis was acute fatty liver of pregnancy. A Caesarean section was performed under epidural anaesthesia, after correction of a coagulopathy. Epidural anaesthesia was chosen because of the potential deleterious effects of general anaesthesia on liver blood flow and function. PMID- 1742828 TI - Persistent sacral nerve root deficits after continuous spinal anaesthesia. AB - Neurological deficits following spinal anaesthesia are rare. We report two cases of persistent sacral nerve root deficits after continuous spinal anaesthesia (CSA) performed with hyperbaric lidocaine through a lumbar microcatheter. In both cases the dose of 5% lidocaine (5.7 and 4.3 ml) was greater than usual. In the immediate postoperative period the constellation of neurological deficits included perianal hypaesthesia, lower extremity paresis, urinary retention, and difficult defaecation. Both patients have residual perianal hypaesthesia and difficult defaecation. In these cases, the high-dose requirements of local anaesthetic via microcatheter CSA with focal sensory block suggests nonuniform distribution of the hyperbaric lidocaine. Microcatheter CSA may convey a unique risk of maldistribution of the local anaesthetic solution and local neurotoxicity. PMID- 1742829 TI - Intraoperative pacemaker failure in an infant. AB - Pacemakers in children can present clinical challenges during surgery. We present a case report of an infant whose pacemaker reverted to a backup mode when electrocautery was used during surgery. The resulting bradycardia did not respond either to a magnet placed over the generator or to iv atropine. The circulation was supported by isoproterenol until the pacemaker was re-programmed by the manufacturer. Such devices require care and understanding if problems during surgery are to be avoided. PMID- 1742830 TI - Acute epiglottitis in the adult: is intubation mandatory? AB - Acute epiglottitis (AE) in the adult results in inflammation of the supraglottic structures and carries the potential for complete airway obstruction. There is disagreement in the medical literature as to the appropriate management of the airway in the adult with AE. Some authors advocate intubation in all patients while others propose more selective intervention, intubating the trachea only in those patients presenting with airway compromise. We reviewed our institutional experience with 21 patients over the last seven years admitted with a proven diagnosis of AE. Six patients presented with respiratory distress, three in severe distress with symptoms and signs of upper airway obstruction. The three patients in severe distress were taken to the operating room, in two the tracheas were intubated and one underwent tracheostomy after failed intubation. All other patients were monitored but their tracheas were not intubated. The majority of the patients were monitored for 24 hr in the ICU before transfer to wards. No patient initially monitored required tracheal intubation for progression of disease. There were no deaths. Recommendations for the care of the airway in the adult with AE based on our experience and a review of approximately 1000 cases reported in the last ten years are presented. It is our opinion that adults presenting without respiratory symptoms may be safely monitored in an intensive care setting given that provision is made for tracheal intubation or tracheostomy should respiratory distress become evident. PMID- 1742832 TI - Abdominal aortic aneurysm repair in a patient with a cardiac transplant. AB - We describe successful elective abdominal aneurysm repair in a patient with a cardiac transplant. In light of the unique physiology and pharmacology of the denervated heart, this presented an unusual combination of complex problems. Whereas the normally innervated heart increases cardiac output via neural stimuli, the denervated heart relies primarily on the Frank Starling mechanism which is dependent on preload and myocardial contractility. Thus, rapidly changing haemodynamic variables associated with aortic cross-clamping require scrupulous attention to the maintenance of adequate preload as well as myocardial function which can only be manipulated by direct-acting agents. We conclude that the denervated heart will readily compensate for the haemodynamic changes brought about by infrarenal aortic crossclamping if a high-normal preload is maintained and if the transplanted donor heart is free of pathology with good inherent myocardial contractility. PMID- 1742831 TI - Postoperative opisthotonus and torticollis after fentanyl, enflurane, and nitrous oxide. AB - Most drug-induced extrapyramidal symptoms are due to blockade of dopaminergic receptors and are treated with anticholinergic drugs. We report a patient with severe postoperative extrapyramidal symptoms which responded to physostigmine and indicated a different aetiology. A young, healthy female outpatient developed severe extrapyramidal symptoms after an uneventful 50 min anaesthetic with thiopentone, fentanyl (100 micrograms), enflurane, and nitrous oxide. Although the trachea was not extubated until she obeyed commands, the patient developed opisthotonus, which resolved initially after treatment with thiopentone (40 mg), diazepam (5 mg), and diphenhydramine (50 mg). The opisthotonus recurred approximately 25 min later, in association with torticollis, obtundation, and periodic apnoea. A tentative diagnosis of central anticholinergic syndrome was proposed, and fentanyl was considered to have been responsible. Naloxone (0.4 mg) induced no improvement, but physostigmine (2 mg) reversed the dystonic symptoms and periodic apnoea and improved her mental status. The response to physostigmine may have been due specifically to increased levels of acetylcholine at the cholinergic receptors, or to a nonspecific analeptic effect. PMID- 1742833 TI - Measurement of cardiac output--transtracheal Doppler versus thermodilution. AB - The ABCOM 1 transtracheal Doppler (TTD) has been developed as a non-invasive cardiac output monitor. With this device, cardiac output is continuously calculated from ascending aortic blood flow velocity and aortic diameter obtained via an ultrasound transducer incorporated into the tip of an endotracheal tube. We evaluated the clinical use of the ABCOM 1 monitor and compared cardiac outputs obtained using the TTD system with simultaneous thermodilution (TD) measurements. We found the operation of the ABCOM 1 monitor to be difficult and time-consuming. In our operating rooms, acceptable Doppler signal quality was difficult to obtain. There was no correlation between 36 simultaneously obtained TTD and TD cardiac output measurements. The average difference between measurement techniques and the limits of agreement were unacceptably large (mean difference = 3.04 L.min-1, mean +/- 2 SD = -6.04 to 12.48 L.min-1). Separately analyzing only those measurements during which Doppler signal quality was adequate did not improve agreement between TTD and TD measurements. On the basis of these findings, TTD cannot be recommended as a clinical cardiac output measurement technique. PMID- 1742834 TI - Deliberate hypotension for intracranial aneurysm surgery: changing practices. PMID- 1742835 TI - Critical incident report: total airway obstruction secondary to design of a tracheostomy set. PMID- 1742836 TI - Uterine relaxation can be life saving. PMID- 1742837 TI - Spinal anaesthesia for caesarean section. PMID- 1742838 TI - A practical, "hands-free" method for mask anaesthesia. PMID- 1742839 TI - Hypocarbia during anaesthesia in children with moyamoya disease. PMID- 1742840 TI - Propofol infusion in carcinoid syndrome. PMID- 1742841 TI - An unusual reaction to precurarization. PMID- 1742842 TI - The TURP syndrome. PMID- 1742843 TI - Plasma and cerebrospinal fluid pharmacokinetics of cytosine arabinoside in dogs. AB - Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS. PMID- 1742844 TI - Effect of bismuth nitrate given in combination with cis diamminedichloroplatinum(II) on the antitumor activity and renal toxicity of the latter in nude mice inoculated with human bladder tumor. AB - The effects of bismuth nitrate pretreatment on the toxicity and antitumor activity of cis-diamminedichloroplatinum (cisplatin, CDDP) were examined in nude mice that had been inoculated with human bladder-tumor tissue. Pretreatment with bismuth nitrate depressed the renal toxicity of CDDP without compromising its activity against a transplantable human bladder tumor. Renal metallothionein (MT) and bismuth (Bi) levels in nude mice were markedly increased by Bi preadministration, but no significant MT induction was observed in inoculated human bladder-tumor tissue in which only a trace amount of Bi was incorporated. Furthermore, it was confirmed that tumor platinum (Pt) concentrations in CDDP treated mice were not affected by Bi pretreatment. Thus, the administration of Bi compounds prior to chemotherapy with CDDP may provide an effective mode of treatment for advanced bladder tumors. PMID- 1742845 TI - Chemosensitisation of a drug-sensitive parental cell line by low-dose cyclosporin A. AB - We investigated the chemosensitisation of the parental EMT6 mouse mammary tumour cell line by low doses of cyclosporin A (CsA). This cell line has not previously been exposed to cytotoxic drugs but expresses low levels of P-glycoprotein. We produced greater than 2-fold sensitisation to doxorubicin, colchicine and vincristine using 0.084 microM (0.1 micrograms/ml) CsA. Cellular accumulation of doxorubicin and daunorubicin was also increased by this dose. In the MDR subline EMT6/AR1.0, much higher doses of CsA were required to effect optimal restoration of doxorubicin or daunorubicin accumulation. The effects of CsA on the parent line could not be increased by extended preincubation of cells with the sensitiser. These effects of CsA in the EMT6 parent cell line occur at a dose that is 1 order of magnitude lower than those previously reported to produce significant chemosensitisation. PMID- 1742846 TI - The relative nephrotoxicity of cisplatin, cis-[Pt(NH3)2(guanosine)2]2+, and the hydrolysis product of cisplatin in the rat. AB - An examination of the comparative nephrotoxicity in the rat of cisplatin, its hydrolysis product (mostly cis-[Pt(NH3)2Cl(H2O)]+ under the conditions applied), and cis-[Pt(NH3)2(guanosine)2]2+ revealed that these compounds differed significantly in the extent of renal damage they produced following their i.v. injection in Sprague-Dawley rats. The hydrolysis product was found to be the most toxic of the three complexes studied and produced nephrotoxicity at doses lower than those at which cisplatin was nephrotoxic. Under the conditions used, the i.v. administration of cis-[Pt(NH3)2(guanosine)2]2+ resulted in no observable signs of nephrotoxicity at levels at which an equimolar dose of cisplatin produces clear evidence of renal function impairment and morphological alterations. The nephrotoxicity of these complexes appears to be generally related to the ease with which they undergo nucleophilic substitution reactions. The lack of substantial nephrotoxicity found for cis-[Pt(NH3)2(guanosine)2]2+ suggests that the products resulting from the action of the DNA repair processes on platinated DNA do not contribute significantly to the nephrotoxicity of cisplatin. Renal platinum levels found following the administration of these compounds correlated with the degree of nephrotoxicity produced by each compound, but no general correlation of nephrotoxicity and renal platinum levels was found. The nephrotoxicity of cis-[Pt(NH3)2Cl(H2O)+ on a molar basis was estimated to be approximately 3 times as great as that of cisplatin itself. PMID- 1742847 TI - Clinical pharmacokinetics of 3-deazaguanine. AB - 3-Deazaguanine (3DG), an antipurine antimetabolite, has recently completed a phase I clinical trial at this Institute. The drug was given on a daily x 5 schedule by i.v. infusion over 0.25-2.16 h. The pharmacokinetics of 3DG during 16 courses were studied in 12 patients at doses of 200-800 mg/m2. 3DG in plasma was measured by an isocratic reverse-phase high-performance liquid chromatographic (HPLC) procedure carried out on IBM phenyl columns at 40 degrees C using 10 mM phosphate buffer (pH 7) as the mobile phase and detection at 300 nm. Plasma decay of 3DG was biexponential in all patients. The AUC correlated linearly with dose at 200-600 mg/m2 but deviated from linearity at doses greater than 600 mg/m2. The drug was cleared rapidly from plasma; at doses of 200-600 mg/m2, the mean plasma clearance was 61.64 +/- 9.97 l/h and the mean terminal-phase elimination half life was 1.6 +/- 0.6 h. The steady-state volume of distribution (98.9 +/- 29.1 l) and distribution coefficient (1.24 +/- 0.39 l/kg) indicated extensive tissue distribution for the drug. No statistically significant difference was observed between the pharmacokinetics of 3DG on day 1 and that on day 4 as evaluated in three patients for whom complete plasma data were available on both days. PMID- 1742848 TI - Pharmacokinetic contribution to the improved therapeutic selectivity of a novel bromoethylamino prodrug (RB 6145) of the mixed-function hypoxic cell sensitizer/cytotoxin alpha-(1-aziridinomethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069). AB - RB 6145 is a novel hypoxic cell sensitizer and cytotoxin containing both an essential bioreductive nitro group and a bromoethylamino substituent designed to form an alkylating aziridine moiety under physiological conditions. In mice, RB 6145 is 2.5 times less toxic but only slightly less active than the aziridine analogue RSU 1069, giving rise to an improved therapeutic index. However, the mechanism for the enhanced selectivity is not clear. Reasoning that this may lie in a more beneficial pharmacokinetic profile, we investigated the plasma pharmacokinetics, tissue distribution and metabolism of RB 6145 in mice using a specially developed reversed-phase HPLC technique. An i.p. dose of 190 mg kg-1 (0.5 mmol kg-1) RB 6145 produced peak plasma concentrations of about 50 micrograms ml-1 of the pharmacologically active target molecule RSU 1069 as compared with levels of around twice this value that were obtained using an equimolar i.p. dose of RSU 1069 itself. The plasma AUC0-infinity value for administered RSU 1069 was ca. 47 micrograms ml-1 h and that for the analogue RSU 1069 was ca. 84 micrograms ml-1 h. No prodrug was detectable. Another major RB 6145 metabolite in plasma was the corresponding oxazolidinone, apparently formed on interaction of the drug with hydrogen carbonate. The oxazolidinone initially occurred at higher concentrations than did RSU 1069, with the levels becoming very similar from 30 min onwards. Post-peak plasma concentrations of both RB 6145 metabolites declined exponentially, displaying an elimination t1/2 of ca. 25 min, very similar to the 30-min value observed for injected RSU 1069. The plasma AUC0 infinity value for the metabolite RSU 1069 was about 1.3 and 1.6 times higher following i.p. injection of 95 mg kg-1 (0.25 mmol kg-1) of the prodrug as compared with administration via the oral and i.v. routes, respectively. After i.v. injection, peak levels of the oxazolidinone metabolite were twice those observed following both i.p. and oral dosing and possibly contributed to the acute toxicity. After an i.p. dose of 190 mg kg-1 RB 6145, concentrations of RSU 1069 and the oxazolidinone metabolites rose to 40% and 33%, respectively, of the ambient plasma level in i.d. KHT tumours. The peak level of metabolite RSU 1069 was ca. 6 micrograms g-1 as compared with 10 micrograms g-1 following an equimolar dose of RSU 1069 itself; the tumour AUC0-infinity value for the metabolite RSU 1069 was some 35% lower.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1742849 TI - Bayesian estimation of doxorubicin pharmacokinetic parameters. AB - Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient. PMID- 1742850 TI - A phase I trial of continuous-infusion cyclophosphamide in refractory cancer patients. AB - Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of less than 500/microliters that lasted for greater than 14 days or thrombocytopenia of less than 25,000/microliters that lasted for greater than 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m2. Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses. PMID- 1742851 TI - Pharmacokinetics of navelbine after oral administration in cancer patients. AB - The pharmacokinetic behavior of navelbine was investigated in 19 patients presenting with advanced cancers (mainly women with breast cancer). Navelbine was given orally at seven dose levels of up to 200 mg/week. For a given dose, patients received four successive weekly treatments. Five subjects also received two different doses. After drug administration, plasma was collected for 48 or 72 h and monitored for navelbine concentration by radioimmunoassay. Absorption of navelbine was very rapid after oral administration: maximal drug concentrations were reached within the first 1 or 2 h (Tmax, 0.9-1.75 h; cmax, 70.9-832.6 ng/ml), with absorption constants ranging from 0.85 to 2.42 l/h. A comparison of dose-normalised plasma concentration profiles revealed significant time dependence in six evaluable patients (P less than 0.001). Only four subjects who received low doses (less than or equal to 100 mg/week) exhibited time-independent kinetics. All of the five patients who were treated at different doses displayed apparent dose dependence (P less than 0.001). No individual profile was characterised by both time- and dose-independent pharmacokinetics. In all, 18 patients presented biphasic plasma concentration-decay patterns, and only 1 subject exhibited monophasic decay kinetics. The navelbine pharmacokinetic parameters obtained following oral administration were similar to those observed after i.v. bolus injection and were characterised by high oral clearance (0.43 1.45 1 h-1 kg-1), a large apparent volume of distribution (27.4-45.9 1/kg), and a long terminal half-life (24.2-56.5 h). Large intra- and inter-individual variations in pharmacokinetic parameters were observed. Moreover, after a high dose of 200 mg, an enterohepatic cycle and/or a delay in navelbine's absorption at a distal intestinal site as evidenced by a marked plasma level rebound was observed. PMID- 1742852 TI - Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells. AB - Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72% +/- 20% survival of cells for epirubicin vs 45% +/- 13% for doxorubicin at a concentration of 0.2 microM; P less than or equal to 0.005). As analyzed by the DiSC assay, 0.2 microM epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival, P less than or equal to 0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 microM, the mean intracellular uptake of epirubicin in leukemic cells was 0.43 +/- 0.26 nmol/mg protein as compared with 0.33 +/- 0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 microM was 0.47 +/- 0.25 nmol/mg protein as compared with 0.31 +/- 0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin. PMID- 1742853 TI - A pharmacokinetic and pharmacodynamic study of the new anthracycline pirarubicin in breast cancer patients. AB - We evaluated the pharmacokinetics of pirarubicin during 16 courses of therapy in 4 patients suffering from breast cancer who were treated with an association of pirarubicin (30-60 mg/m2 according to the hematologic tolerance to the previous course, the first course being given at a dose of 40 mg/m2) and continuous infusions of 5-fluorouracil (750 mg/m2 daily for 5 days). Pirarubicin's pharmacokinetics and metabolism were linear within this dose range; the metabolites identified were pirarubicinol, doxorubicin and doxorubicinol (AUC ratios of metabolite/pirarubicin were 0.6, 0.64 and 0.57 respectively). Pirarubicin's decay from plasma followed a two-compartmental pattern, showing half-lives of 15.6 min and 16.6 h; the total plasma clearance of the drug was 140 l/h-1/m-2, and the total volume of distribution was 2,830 l/m2. A relationship was observed between some pharmacokinetic parameters and the toxic effects of the drug: the percentage of survival of granulocytes was significantly correlated with the AUC values for doxorubicin and doxorubicinol, whereas that of platelets was significantly correlated with the AUC values for pirarubicin and pirarubicinol. This is the first study to demonstrate a pharmacokinetic/pharmacodynamic relationship for pirarubicin. PMID- 1742854 TI - Etoposide, folinic acid, and 5-fluorouracil in carboplatin-pretreated patients with advanced gastric cancer. AB - A group of 20 patients with gastric cancer, refractory to or with no change after two or three cycles of carboplatin were treated with etoposide/folinic acid/5 fluorouracil (ELF). An objective remission rate of 45% (9/20), a median remission duration of 8 months and a median survival time of 11 months were achieved. Toxicities were mild to moderate only. These results are comparable to those being achieved with ELF in previously untreated gastric cancer patients and confirm its efficacy and good tolerability. PMID- 1742855 TI - Positive phase II study in the treatment of advanced malignant melanoma with fotemustine. AB - To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected. PMID- 1742856 TI - Interactions between platelet-activating factor and prostanoids during mesenteric ischemia-reperfusion-induced shock in the anesthetized dog. AB - The effects of platelet-activating factor (PAF) on prostanoid release during mesenteric ischemia-reperfusion-induced shock were investigated in anesthesized dogs 1) by measuring plasma levels of prostaglandin (PG)F2 alpha, 6-keto-PGF1 alpha and thromboxane (TX)B2 in the superior mesenteric vein during reperfusion following 2 hr occlusion of the superior mesenteric artery; 2) by monitoring the effects of BN 52021, a specific PAF receptor antagonist and indomethacin on hemodynamic parameters and prostanoid levels; and 3) by studying circulatory responses to PAF and PGF2 alpha injected into the superior mesenteric vein in the presence of BN 52021 or indomethacin. Restoration of the blood flow following 2 hr ischemia resulted in an immediate dramatic decrease in mean arterial blood pressure, with a concomitant increase in mean portal venous pressure, hematocrit values, and plasma prostanoid levels. Pretreatment of the animals either with BN 52021 (4 mg.kg-1) or indomethacin (2 mg.kg-1 plus 3 mg.kg-1hr-1) prevented the circulatory collapse and the increase in prostanoid levels during reperfusion. Administration of exogenous PAF (0.1 micrograms.kg-1) or PGF2 alpha (10 micrograms.kg-1) into the superior mesenteric vein evoked hypotension similar to that observed during reperfusion. Pretreatment of the animals with BN 52021 completely prevented the effects of PAF but failed to modify the responses to PGF2 alpha. Indomethacin at a dose that inhibited prostanoid formation was highly effective to attenuate the hypotensive response to exogenous PAF. These data suggest that prostanoid formation may be secondary to PAF release in circulatory collapse evoked by intestinal ischemia-reperfusion and give further support to the notion of the importance of PAF prostanoid interaction during ischemia reperfusion-induced shock. PMID- 1742857 TI - Cardiac output and organ blood flow in experimental septic shock: effect of treatment with antibiotics, corticosteroids, and fluid infusion. AB - Septic shock from intraperitoneal (i.p.) injection of live Escherichia coli bacteria in rats induces marked pathophysiological changes, including 40% decrease in plasma volume (PV), cardiac output, and oxygen consumption with 100% mortality within 24 hr. The present study evaluates cardiac output and organ blood flow before and after treatment of septic shock with an effective antibiotic (AB), plasma volume (PV) expansion, and corticosteroids (CS), alone and in combination. Treatment was initiated at 5.5 hr after bacterial injection, at a time when AB therapy did not improve 24 hr survival rate. Cardiac output decreased from 28.6 +/- 3.1 (SD) to 15.4 +/- 2.8 ml/min/kg (P less than .01) in septic rats concomitant with redistribution of blood flow from carcass to the heart, brain, intestines, liver, and adrenal glands. Absolute arterial blood flow increased only to the adrenal glands and the liver to 158% (P less than .01) and 167% (P less than .01) of control values, respectively. AB, CS, and Ringer's lactate (RL) alone or in combination did not significantly improve any organ blood flow compared to untreated septic animals but increased survival significantly to about 60% (P less than .01). Albumin (ALB) and CS in combination expanded PV to 138% (P less than .01), restored cardiac output to 100%, and achieved supranormal blood flow values to the brain (109%), liver (125%), small intestine (147%) (P less than .01), and kidneys (190%) (P less than .01) of preshock levels. More importantly, survival at 24 hr was 90% (9/10) (P less than .001). It is concluded that a colloid diluted in an electrolyte solution, combined with CS, and an effective antibiotic agent are necessary therapeutic ingredients for the successful recovery of experimental E. coli sepsis. PMID- 1742858 TI - Endothelial-dependent and -independent responses in the thoracic aorta during endotoxic shock. AB - Endotoxic shock is characterized by a variety of hemodynamic disturbances which result in tissue hypoperfusion. There is some evidence for endothelial damage caused by endotoxin. The present study addressed the hypothesis that vascular responsiveness to endothelial-dependent vasodilators is altered in endotoxic shock. Dose-response relationships for an endothelial-dependent vasodilator, acetylcholine, and an endothelial-independent vasodilator, adenosine, were determined in guinea pig aortic rings. Rings were examined from either control (untreated) animals or from animals given Escherichia coli endotoxin (4 mg/kg, i.p.) 16 hr prior to functional studies. Dose-response relationships to adenosine were similar in aortic rings from control and shocked animals. However, response to acetylcholine were attenuated by 30% (P less than .05) in the shocked group. To distinguish between a direct, acute effect of endotoxin versus effects produced by systemic changes that occur during shock, rings were isolated from untreated animals and incubated with endotoxin in vitro for 30 min prior to and during dose-response measurements. Incubation with endotoxin caused no change in aortic responses to adenosine or acetylcholine. Electron microscopy revealed a separation of the endothelium from the internal elastic lamina and an increase in inter-endothelial gaps in rings isolated from shocked animals. These structural changes were not observed in rings from untreated animals or in rings incubated with endotoxin in vitro. We conclude that endothelial-dependent vasodilation is attenuated during endotoxic shock. The functional changes are correlated with ultrastructural alterations of the endothelium. PMID- 1742859 TI - Cardiac function in an ovine model of endotoxemia. AB - Eight awake sheep were monitored with ultrasonic crystals, positioned at the anterior and posterior left ventricular wall. A left-sided intraventricular pressure transducer and a right ventricular ejection fraction catheter were positioned in the right and left hearts, respectively. After administration of endotoxin (Escherichia coli, LPS 1.5 micrograms/kg in 30 min), the hemodynamic variables showed a triphasic course. Phase I, (0-1 hr post LPS) was characterized by an increased pulmonary artery pressure and a decreased right ventricular ejection fraction. The inability of the right ventricle to compensate for the increased preload resulted in a fall of the left ventricular preload, stroke volume, and cardiac output. Three hours after LPS administration a second drop of the cardiac output was noted (phase II). This occurred as a result of a fall in preload. Eight hours post LPS a hyperdynamic phase (phase III) was distinguished, with a high cardiac output and a low systemic vascular resistance. During this time there was evidence of probable reduced myocardial contractility. PMID- 1742860 TI - Systemic and mesenteric O2 metabolism in endotoxic pigs: effect of graded hemorrhage. AB - Normally, supply-dependency of oxygen uptake (VO2) is not demonstrable unless oxygen delivery (DO2) is less than a critical value (DO2crit) below which VO2 is linearly dependent upon DO2. Because recent evidence suggests that VO2 is pathologically supply-dependent in endotoxic or septic animals and humans, we sought to determine whether 1) pathological systemic and/or mesenteric oxygen extraction (O2EXT) defects occur in a porcine model of endotoxicosis and 2) arterial lactate and ileal intramucosal pH (pHI) serve as useful markers of supply-dependency of VO2 in endotoxic animals. Normal (group I, n = 11) and endotoxic (group II, n = 8) anesthetized pigs were subjected to graded hemorrhage. Endotoxicosis was induced by infusing Escherichia coli lipopolysaccharide (150 micrograms/kg bolus at t = 0 min and 20 micrograms/kg-hr at t = 60 min). From t = 0-60 min, pigs in group II were resuscitated with hetastarch and blood (12 ml/kg each). Hemorrhage was initiated at t = 0 min or t = 70 min in groups I and II, respectively. DO2crit was determined by a modified "dual-line" regression method. Systemic DO2crit was 12.9 +/- 0.9 ml/kg-min in group I and 16.9 +/- 1.3 ml/kg-min in group II (P less than .05). Systemic O2EXT at DO2crit was similar in both groups. Arterial lactate concentration at DO2crit was significantly higher in endotoxic pigs (group I, 2.64 +/- 0.29 mM; vs. group II, 3.88 +/- 0.45 mM; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742861 TI - Prophylaxis and treatment of newborn endotoxic shock with anti-lipid A monoclonal antibodies. AB - The newborn is very susceptible to gram-negative sepsis/septic shock. The mortality of newborn endotoxic shock continues to be high. Since lipid A is responsible for the toxic effects of lipopolysaccharide, anti-lipid A antibodies may prevent endotoxic shock in the newborn. This study showed that both anti lipid A monoclonal IgG (A78S1) and anti-lipid A monoclonal IgM (A523) decreased the mortality of endotoxic shock in 10 day old rats. Prophylactic administration of A78S1 and A523 to the pregnant rat decreased the mortality of endotoxic shock in their 0-day-old offspring. Prophylaxis was due to transplacental passage of A78S1 treatment. The mechanism of prophylaxis remains unclear in A523 treatment. PMID- 1742862 TI - Effect of injured vessel size on bleeding following hypertonic saline infusion in "uncontrolled" hemorrhagic shock in anesthetized rats. AB - Hypertonic saline (HTS) infusion in "uncontrolled" hemorrhagic shock (UCHS) leads to increased bleeding from injured vessels, fall in mean arterial pressure (MAP), and early mortality. The effect of injured vessel size on blood loss in response to HTS treatment was studied in Neurolidal Ketalar anesthetized Hebrew University strain rats. The animals were randomly assorted into 4 groups: In group I (n = 8) UCHS was induced by resection of 8% of the terminal portion of the rats' tail and the animals were untreated. In group II (n = 8) UCHS was induced as in group I and the animals were treated with 5 ml/kg NaCl 7.5% (HTS). In group III (n = 9) UCHS was induced by 50% resection of the animal's tail, and the animals were untreated. In group IV (n = 12) UCHS was induced as in group III and the animals were treated with 5 ml/kg HTS Resection of 8% of the animal's tail was followed by bleeding of 2.6 +/- 0.3 ml and fall in MAP from 107 +/- 7 to 80 +/- 10 torr (P less than .005) within 5 min. Resection of 50% of the animal's tail was followed by bleeding of 4.3 +/- 0.4 ml (P less than .01) and fall in MAP to 41 +/- 6 torr (P less than .001) after 5 min. Infusion of HTS in group II was followed by further blood loss of 4.9 +/- 07 ml within 4 hr while in untreated group I, blood loss was only 3.4 +/- 0.4 ml (P less than .05), MAP remained unchanged, and there was no mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742863 TI - Mechanical manifestations of activation in cardiac muscle. PMID- 1742864 TI - Fatty acid metabolism and contractile function in the reperfused myocardium. Multinuclear NMR studies of isolated rabbit hearts. AB - The hypothesis that substrate availability can alter contractile function in reperfused myocardium after global ischemia was investigated in this study. Isolated rabbit hearts were placed in a dual tuned (31P/13C) NMR probe with a 9.4 T magnet and perfused with the following substrates given individually or in combination: 10 mM glucose, 2 mM palmitate, and 2.5 mM [3-13C]pyruvate. Glucose was the sole substrate present for all groups of hearts before the onset of 10 or 20 minutes of zero-flow ischemia. Contractility (dP/dt) was significantly higher in hearts reperfused with glucose compared with hearts reperfused with palmitate or the combination. In addition, myocardial oxygen consumption/unit of work at reperfusion was more efficient with glucose than with palmitate. ATP content during reperfusion was similar with glucose and palmitate and did not account for improved function with glucose. To determine if inhibition of pyruvate metabolism by palmitate might result in altered postischemic function, additional hearts were reperfused with 2.5 mM [3-13C]pyruvate provided alone or in combination with palmitate. Using 13C NMR spectroscopy, it was shown that with the addition of palmitate, pyruvate oxidation was decreased in control and 10-minute ischemic hearts as is consistent with inhibition of pyruvate dehydrogenase by fatty acids. However, palmitate/pyruvate did not worsen postischemic function as compared with palmitate or pyruvate alone. Tricarboxylic acid cycle activity was slowed in reperfused pyruvate hearts, but no further reduction was observed when palmitate was present. In conclusion, palmitate reduces the mechanical function of the reperfused isolated rabbit heart as compared with glucose. This effect of palmitate does not appear to be caused by suppression of pyruvate oxidation or by a change in high energy phosphate content. PMID- 1742865 TI - Coronary microvascular resistance in hypertensive cats. AB - Chronic systemic hypertension has been shown to alter the distribution of vascular resistance in many microvascular beds. The purposes of this study were to assess the effects of chronic systemic hypertension on the pressure distribution in the coronary microcirculation and to determine the microvascular site where coronary vascular resistance is increased. Cats were made hypertensive using a one-kidney, one-wrap model (Page model). A servonulling system was used to directly measure pressures in the epimyocardial microvessels of the beating left ventricle in normotensive and hypertensive cats. In chronically hypertensive cats, mean arterial pressure was 153 +/- 5 mm Hg compared with 98 +/- 3 mm Hg in normotensive cats (p less than 0.05). Left ventricular mass was increased approximately 34% in hypertensive cats (9.4 +/- 0.3 versus 7.0 +/- 0.3 g, p less than 0.05). Myocardial perfusion measured using radiolabeled microspheres was not different between hypertensive and normal cats. Coronary vascular resistance of the left ventricle was increased in hypertensive cats (0.90 +/- 0.08 versus 0.66 +/- 0.05 mm Hg x min x 100 g/ml, p less than 0.05). Microvascular pressures were measured in three groups of microvessels: small, less than 200 microns; medium, 200-300 microns; and large, greater than or equal to 300 microns. Mean microvascular pressures of large, medium, and small arterial microvessels in hypertensive cats were 144 +/- 8, 127 +/- 6, and 115 +/- 7 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742866 TI - Comparison of crossbridge dynamics between intact and skinned myocardium from ferret right ventricles. AB - This study compares the crossbridge kinetics of intact and skinned preparations from ferret cardiac muscles at 20 degrees C to determine whether skinning causes any alteration in the crossbridge response to an imposed length change. A papillary or trabecular muscle was isolated from the right ventricle, the muscle length adjusted to give the maximum twitch tension (Lmax), and the preparation was subjected to Ba2+ contracture. When steady tension developed, the length of the preparation was perturbed sinusoidally in 19 discrete frequencies, ranging from 0.13 to 135 Hz, and at a small peak-to-peak amplitude (0.25% Lmax). We identified three exponential processes in the sinusodial force-response to the imposed length oscillation, and these were labeled processes B, C, and D in order of increasing speed. A slow process, A, normally present in fast-twitch skeletal muscles, is very small or absent in cardiac muscles. Process B is an exponential delay, and the muscle produces oscillatory work on the forcing apparatus; processes C and D are exponential advances in which the muscle absorbs work. The preparation was chemically skinned and activated in the presence of (mM) CaEGTA 6 (pCa 4.55), MgATP 5, magnesium propionate 1, and phosphate 1, pH 7.0, with ionic strength adjusted to 200 mM with potassium propionate. We found that the crossbridge kinetics were not altered by the skinning procedure. The apparent rate constants extracted from the sinusoidal analysis were nearly identical in Ba2+ contracture (intact preparation) and in Ca2+ activation (skinned preparation), and the Nyquist plots were similar. Because the rate constants changed sensitively with the substrate (MgATP) concentrations, we concluded that the substrate is adequately supplied during Ba2+ contracture in the intact preparation. Our study demonstrates the compatibility of results obtained from an intact and from a skinned preparation. PMID- 1742867 TI - Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine. AB - The quantification of adenine nucleotides released from the heart is hampered by their rapid dephosphorylation to adenosine in the extracellular space catalyzed by highly active ectonucleotidases. To determine the total release of adenine nucleotides from isolated Langendorff-perfused guinea pig hearts, ecto 5' nucleotidase was effectively blocked by infusion of alpha, beta-methylene-ADP (AOPCP, 50 microM). Adenine nucleotides were measured in the coronary venous effluent by the luciferin-luciferase method after enzymatic rephosphorylation to ATP. In hearts perfused at a constant flow rate (10 ml/min) with normoxic buffer (95% O2, 5% CO2) the release +/- SEM of adenine nucleotides and adenosine was 0.06 +/- 0.01 (n = 11) and 0.04 +/- 0.01 (n = 13) nmol/min. In the presence of AOPCP, the release of adenine nucleotides increased to 0.43 +/- 0.04 nmol/min (n = 9; p less than 0.05), whereas adenosine remained unchanged. Hypoxic perfusion (10% O2, 85% N2, 5% CO2) caused a threefold increase in adenine nucleotide release but a 40-fold increase in adenosine. In contrast, global ischemia (30 seconds) caused adenine nucleotide and adenosine release to rise to similar values of 1.06 +/- 0.10 and 0.80 +/- 0.14 nmol/min (n = 9). Stimulation of hearts with isoproterenol (4 nM) likewise increased the release of adenine nucleotides (0.50 +/- 0.04 nmol/min) and adenosine (0.87 +/- 0.21 nmol/min) (n = 6). To determine the cellular source of adenine nucleotides released from the heart, the coronary endothelial adenine nucleotide pool was selectively prelabeled by [3H]adenosine. Global ischemia increased the specific radioactivity of released adenine nucleotides by 57%. The findings indicate that 1) adenine nucleotides and adenosine are released at the same order of magnitude from the well-oxygenated heart; 2) beta-adrenergic stimulation and ischemia stimulate the release of adenine nucleotides and adenosine, both purines reaching vasoactive concentrations in the effluent perfusate; 3) during hypoxic perfusion only the release of adenosine is greatly enhanced; and 4) the coronary endothelium preferentially contributes to the ischemia-induced adenine nucleotide release. PMID- 1742868 TI - Effects of TA-3090, a new calcium channel blocker, on myocardial substrate utilization in ischemic and nonischemic isolated working fatty acid-perfused rat hearts. AB - Experimental studies have shown that calcium channel blockade has a protective effect on the ischemic myocardium. Although these agents may act by decreasing intracellular Ca2+ accumulation during reperfusion or to reduce oxygen requirements by decreasing myocardial work load, recent evidence suggests that calcium blockers may also favorably alter energy substrate metabolism in ischemic and reperfused myocardium. In this study, TA-3090, a new calcium channel blocker with minimal effect on myocardial work load, was used to study the effect of calcium channel blockade on both myocardial substrate utilization and reperfusion recovery of ischemic hearts. Isolated working rat hearts were perfused at an 11.5 mm Hg preload and an 80 mm Hg afterload with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microunits/ml insulin. In aerobically perfused spontaneously beating hearts, a 0.5 microM dose of TA-3090 had a mild depressant effect on heart rate but no effect on peak systolic pressure development. In paced hearts (250 beats/min), 0.5 microM TA-3090 had no effect on either peak systolic pressure development or contractility. Fatty acid and glucose oxidation was determined by measuring 14CO2 production in hearts perfused with either [14C]palmitate or [14C]glucose, respectively, whereas glycolysis was determined by measuring 3H2O production from [3H]glucose. Under aerobic conditions, fatty acid oxidation was not altered by TA-3090, but a significant decrease in glucose oxidation and glycolytic rates was observed. If hearts were subjected to a 30-minute period of no-flow ischemia, the addition of 0.5 microM TA-3090 to the perfusate before ischemia significantly improved reperfusion recovery of mechanical function. The protective effects of TA-3090 were not observed if TA-3090 was added at the time of reperfusion and were not related to a depression of function before ischemia. TA-3090, added before ischemia, significantly reduced glycogen and ATP depletion during no-flow ischemia and also significantly decreased glycolytic rates in hearts subjected to low-flow ischemia (coronary flow = 0.5 ml/min). Combined, our data suggest that the beneficial effects of calcium channel blockade on the ischemic myocardium are not related solely to a decrease in myocardial work load or metabolic demand before ischemia, but rather may in part be related to a decrease in myocardial energy demand during ischemia itself, resulting in preservation of ATP and a decrease in glycolysis. The decrease in glycolytic rates during ischemia may also result in a reduction of glycolytic product accumulation during ischemia. PMID- 1742869 TI - Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species. AB - Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover. PMID- 1742870 TI - Mechanisms responsible for the heterogeneous coronary microvascular response to nitroglycerin. AB - Nitroglycerin dilates large (greater than or equal to 100 microns) but not small coronary arterial microvessels, and a putative metabolite of nitroglycerin, S nitroso-L-cysteine, has been shown in vitro to dilate both large and small coronary microvessels. Based on this evidence, we tested the hypothesis that the lack of response of small coronary microvessels was due to an inability of small coronary microvessels to convert nitroglycerin into its vasoactive metabolite and examined possible explanations for this phenomenon. We studied left ventricular epicardial microvessels in vivo using video microscopy and stroboscopic epi illumination in anesthetized, open-chest dogs. Diameters were determined while the epicardium was suffused with nitroglycerin, S-nitroso-L-cysteine, or S nitroso-D-cysteine (all 10 microM) and nitroglycerin in the presence of L- or D cysteine (100 microM). None of the agents affected systemic hemodynamics. Nitroglycerin dilated large arterioles (20 +/- 2%) but not small arterioles (1 +/ 1%). Both S-nitroso-L-cysteine and S-nitroso-D-cysteine were potent dilators of all size classes of microvessels. Concomitant application of L-cysteine and nitroglycerin evoked dilation in small microvessels (22 +/- 4%, p less than 0.5 versus nitroglycerin alone) and larger microvessels (27 +/- 6%, p = NS versus nitroglycerin alone). D-Cysteine did not alter the microvascular response to nitroglycerin in either small (7 +/- 4%, p = NS versus nitroglycerin alone) or large (18 +/- 3%, p = NS versus nitroglycerin alone) microvessels. Neither L cysteine nor D-cysteine had a direct effect on microvascular diameter. These findings suggest that 1) sulfhydryl groups are required for the conversion of nitroglycerin to its vasoactive metabolite; 2) the interaction between nitroglycerin and sulfhydryl residues is a stereospecific process, indicating either an intracellular mechanism or a membrane-associated enzymatic reaction; and 3) a lack of available sulfhydryl groups may be responsible for the lack of response of small coronary arterioles to nitroglycerin. PMID- 1742871 TI - Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. AB - To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased ninefold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Chamber dilation was the consequence of the combination of gross anatomic and cellular changes consisting, in the presence of small infarcts, of a 6% and a 19% increase in transverse midchamber diameter and in average myocyte length per nucleus, respectively. In the presence of large infarcts, transverse and longitudinal chamber diameters expanded by 27% and 11%, respectively, myocyte length per nucleus expanded by 26%, and the mural number of myocytes decreased by 10%. In conclusion, decompensated eccentric ventricular hypertrophy develops chronically after infarction, and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistance of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure. PMID- 1742872 TI - Digital angiographic impulse response analysis of regional myocardial perfusion. Estimation of coronary flow, flow reserve, and distribution volume by compartmental transit time measurement in a canine model. AB - A system impulse response function that describes the kinetics of radiographic contrast material transit through the coronary circulation was calculated from 175 selective digital angiograms of normal and stenotic arteries in 10 dogs during rest and hyperemia. The goal of the study was to determine if the flow and distribution volume characteristics of the epicardial coronary arteries and the myocardial microcirculation could be stimulated by specific mathematical compartments of a lagged normal density model impulse response function in which the flow/distribution volume ratio is the inverse of the mean transit time. The arterial compartment mean transit time correlated with flow (r = 0.75); however, the correlation was significantly improved in individual dogs (r = 0.83 +/- 0.13; p less than 0.005) and was highly dependent on the length of the conduit vessel. The microcirculation compartment mean transit time was distributed as two populations with respect to flow. There was a linear correlation during hyperemia (r = 0.87) and a nonlinear relation during rest, which was characteristic of an autoregulating system. Resting values of microcirculation compartment mean transit time correlated with coronary flow reserve (r = 0.84) and differed significantly between vessels that were normal and those with subcritical stenosis, critical stenosis, or total occlusion (p less than 0.01 for all comparisons). The estimated microcirculation compartment distribution volume increased from a minimum of 4.0 +/- 1.5 ml/100 g myocardium in normal vessels with resting flow to 11.2 +/- 3.5 ml/100 g during hyperemia. These data suggest that the model compartments functionally describe the physiological behavior of their anatomic analogues and permit the quantification of microcirculatory autoregulation from a single measurement at rest without provoking hyperemia. PMID- 1742873 TI - Platelet and fibrin modification by radiographic contrast media. AB - The effect of the radiographic contrast agents, iopamidol and diatrizoate, on fibrin assembly and structure as well as platelet surface charge was studied. Increasing the iopamidol concentration from 0 to 4.5 mM prolongs the fibrin gelation time from 20 to 105 seconds (an anticoagulant effect) and reduces the fibrin fiber mass/length ratio from 3.2 x 10(12) to 0.5 x 10(12) Da/cm (i.e., produces very thin fibrin fibers). Ultraviolet difference spectroscopy of fibrinogen showed both a 15-nm shift in the ultraviolet difference maximum for iopamidol (suggesting binding) and a perturbation of the aromatic amino acid side chain region for fibrinogen (suggesting a conformational change in fibrinogen) as the concentration of iopamidol was increased from 0 to 9 mg/ml. Binding of iopamidol to fibrinogen was also shown by affinity chromatography using a Sepharose-fibrinogen column. Electrophoretic quasi elastic light scattering was used to show platelet interaction with iopamidol as reflected in a reduction in the platelet electrophoretic mobility from 2.0 to 0.5 (microns-cm)/(V-sec) as the concentration of iopamidol was increased from 0 to 4.5 mM. In addition, the ionic radiopaque contrast agent, Renografin, was also studied and found to inhibit fibrin monomer assembly. Although iopamidol is not shown to be thrombogenic, iopamidol does appear to reduce platelet surface charge, bind fibrinogen, and modify fibrin clot structure. PMID- 1742874 TI - Ryanodine does not affect calcium current in guinea pig ventricular myocytes in which Ca2+ is buffered. AB - Calcium current in mammalian ventricular muscle is altered in the presence of ryanodine. Previous studies performed on rat ventricular cells have shown a slowing of Ca2+ current inactivation and suggest the hypothesis that ryanodine, by reducing the release of Ca2+ from the sarcoplasmic reticulum, reduces the availability of Ca2+ for inactivation of Ca2+ current (Ca(2+)-dependent inactivation). Another hypothesis is that the effects of ryanodine on Ca2+ current are due to a mechanical connection of the ryanodine receptor with the L type Ca2+ channel. To further test these hypotheses we examined the effect of ryanodine on Ca2+ current in single voltage-clamped guinea pig ventricular myocytes that contained Ca2+ indicator and Ca2+ buffer. We used fura 2 (pentapotassium salt) to confirm that the ryanodine we used was capable of abolishing Ca2+ release from the sarcoplasmic reticulum during the period in which it was present. We perfused the cells with 10 mM EGTA to block changes in intracellular Ca2+ concentration. In the absence of internal EGTA, Ca2+ currents displayed biexponential inactivation and Ca(2+)-dependent inactivation (steady state inactivation curves turned up at positive potentials). Inactivation was slowed by ryanodine at 10 microM. In cells perfused internally with EGTA, however, ryanodine had no effects, and steady-state inactivation curves were not shifted to the right. We conclude that, in guinea pig ventricular myocytes, the effects of ryanodine on Ca2+ current are mediated by Ca2+ and thus the effects of ryanodine do not provide a basis on which to postulate a physical connection between the L-type Ca2+ channel and the ryanodine receptor (sarcoplasmic reticulum Ca2+ release channel). PMID- 1742875 TI - Does load dependence of relaxation differ between left and right cardiac muscle? PMID- 1742876 TI - Bioactive gonadotrophin secretion in man. PMID- 1742877 TI - Iodine-131 treatment of hyperthyroidism: current issues. PMID- 1742878 TI - Thirst and vasopressin. PMID- 1742879 TI - Osmotic and non-osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking. AB - OBJECTIVE: To examine the osmotic and non-osmotic regulation of thirst and AVP release in patients with compulsive water drinking. DESIGN: A 2-hour intravenous infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2 hour drinking period. PATIENTS: Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls. MEASUREMENTS: Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following infusion. RESULTS: Plasma AVP responses to osmotic stimulation, and non-osmotic inhibition by drinking, were normal in patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P less than 0.001) or controls (P less than 0.001), despite lower basal plasma osmolalities. There was a significant rise in thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than in either diabetes insipidus (P less than 0.01) or controls (P less than 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus. CONCLUSIONS: There are abnormalities of the osmotic stimulation and non-osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non-osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic information in the differentiation of polyuric states. PMID- 1742880 TI - Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto's thyroiditis. AB - OBJECTIVE: It has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto's thyroiditis but no objective data are available. We have therefore investigated the influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxidase antibodies. DESIGN: Consecutive patients with goitrous Hashimoto's thyroiditis was studied. PATIENTS: Thirteen women participated; all had goitrous thyroiditis. TREATMENT: To render them euthyroid thyroxine was given for 24 months. MEASUREMENTS: Thyroid size was measured ultrasonically and antithyroid peroxidase antibodies were measured using a commercial radioimmunological method. RESULT: Concomitant with the gradual increase in serum free thyroxine and free triiodothyronine index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 +/- 6.8 ml (mean +/- SEM) to 34.1 +/- 5.7 ml (32%), P less than 0.001 was demonstrated. Antithyroid peroxidase antibodies were present in high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after initiation of treatment. CONCLUSION: A clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved during L-thyroxine treatment of hypothyroid goitrous Hashimoto's thyroiditis. PMID- 1742881 TI - Pituitary macroadenomas associated with hyperprolactinaemia: immunocytochemical and in-situ hybridization studies. AB - OBJECTIVE: We have assessed whether in-situ hybridization for prolactin messenger RNA (mRNA) provides additional information for the classification of pituitary macroadenomas associated with hyperprolactinaemia. DESIGN: In-situ hybridization for PRL mRNA was performed on surgical biopsies of pituitary adenomas and the results correlated with serum PRL levels and PRL immunoreactivity. PATIENTS: Twenty-one patients (11 men, 10 women) were included; five had normal serum PRL levels, 11 mild hyperprolactinaemia (less than 3000 mU/l) and five marked hyperprolactinaemia (greater than 3000 mU/l). MEASUREMENTS: Immunocytochemistry for PRL and in-situ hybridization for PRL mRNA were performed on surgical biopsies. RESULTS: Immunoreactivity for PRL was detected in tumours from all patients with serum PRL greater than 3000 mU/l and in one of 11 patients with mild hyperprolactinaemia. Positive signal for PRL mRNA was detected in four of five immunopositive cases studied, in a further two cases with mild hyperprolactinaemia, and in one tumour associated with normal serum PRL level. CONCLUSIONS: In-situ hybridization provides evidence of PRL gene activation in the absence of immunoreactivity for prolactin. This may reflect low levels of hormone storage or defective translation of the mRNA. PMID- 1742882 TI - A distribution method for analysing the baseline of pulsatile endocrine signals as exemplified by 24-hour growth hormone profiles. AB - OBJECTIVE: To develop a method for quantifying the distribution of concentrations present in hormone profiles, which would allow an observer-unbiased estimate of the time concentration attribute and to make an assessment of the baseline. DESIGN: The log-transformed concentrations (regardless of their temporal attribute) are sorted and allocated to class intervals. The number of observations in each interval are then determined and expressed as a percentage of the total number of samples drawn in the study period. The data may be displayed as a frequency distribution or as a cumulative distribution. Cumulative distributions may be plotted as sigmoidal ogives or can be transformed into discrete probabilities (linear probits), which are then linear, and amenable to regression analysis. Probability analysis gives estimates of the mean (the value below which 50% of the observed concentrations lie, which we term 'OC50'). 'Baseline' can be defined in terms of percentage occupancy--the 'Observed Concentration for 5%' (which we term 'OC5') which is the threshold at or below which the hormone concentrations are measured 5% of the time. PATIENTS: We report the use of applying this method to 24-hour growth hormone (GH) profiles from 63 children, 26 adults and one giant. RESULTS: We demonstrate that GH effects (growth or gigantism) in these groups are more related to the baseline OC5 concentration than peak concentration (OC5 +/- 95% confidence limits: adults 0.05 +/- 0.04, peak-height-velocity pubertal 0.39 +/- 0.22, giant 8.9 mU/l). CONCLUSIONS: Pulsatile hormone profiles can be analysed using this method in order to assess baseline and other concentration domains. PMID- 1742883 TI - Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome. AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen transport and metabolism in women with PCOS. DESIGN: Within-group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women. PATIENTS: Forty-seven women who presented with hirsutism, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6 +/- 0.7 years (mean +/- SEM), BMI 27.3 +/- 1.2 kg/m2. MEASUREMENTS: Plasma insulin levels were measured at 30-minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (fT), sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS: Neither basal insulin nor the sum of insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with irregular cycles or amenorrhoea than in those with regular ovulatory menses (8.0 +/- 1.1 vs 3.1 +/- 1.5 mU/l, P less than 0.01) despite similarly raised androgen levels. Both basal insulin and sumINS correlated with BMI in women with PCO (r = 0.37, P less than 0.05 and r = 0.64, P less than 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF-I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an inverse correlation and fT correlated positively with sumINS (r = -0.51, P less than 0.01; r = 0.39, P less than 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens. CONCLUSIONS: These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes in SHBG rather than by direct stimulation of ovarian androgen production. Higher insulin concentrations in anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that insulin resistance in the ovary contributes to the mechanism of anovulation in PCOS. PMID- 1742884 TI - The short Synacthen test in acute hospital admissions. AB - OBJECTIVE: We wished to define the cortisol response to 250 micrograms intramuscular tetracosactrin (Synacthen) in acute hospital admissions, using a modern immunoassay for cortisol. DESIGN: We performed a prospective study of, as near as possible, a consecutive series of 161 admissions to a single unit. PATIENTS: We studied 50 patients (age range 67-98, mean 80.3 years, 31-female, 19 male) admitted as an emergency, from whom it was possible to obtain informed consent, and whom it was possible to study within 24 hours of admission. MEASUREMENTS: We measured baseline, increment and peak serum cortisol following administration of 250 micrograms intramuscular tetracosactrin between 0800 and 0900 hours. RESULTS: Baseline cortisol concentrations ranged from 288 to 1585 nmol/l (mean 706; median 665). Peak cortisol concentrations ranged from 602 to 2265 nmol/l (mean 1076; median 999). Baseline and peak cortisol concentrations showed a significant correlation (P less than 0.001). Increment varied from 10 to 747 nmol/l (mean 374; median 336) and did not correlate with baseline. CONCLUSIONS: In acute hospital admissions, baseline serum cortisol between 0800 and 0900 hours should exceed 250 nmol/l. Peak serum cortisol after 250 micrograms intramuscular tetracosactrin should exceed 600 nmol/l. Calculation of the increment is of no value. PMID- 1742885 TI - Long-term follow-up of hypothalamic-pituitary function in patients with transsphenoidal pituitary herniation and midfacial anomalies. AB - OBJECTIVE: We wished to determine whether patients with transsphenoidal pituitary herniation were at risk of developing pituitary failure. DESIGN: We followed up hypothalamic-pituitary function annually in patients with midfacial anomalies and pituitary herniation. PATIENTS: Two patients who had transsphenoidal pituitary herniation and midfacial anomalies were included and the literature was reviewed. RESULTS: Both patients became gonadotrophin, TSH and growth hormone-deficient despite neurosurgical repair. CONCLUSION: We conclude that the early diagnosis and neurosurgical repair of transsphenoidal pituitary herniation may prevent central nervous system infection and rhinorrhoea. Surgical repair may not prevent pituitary failure as was evident in both of our cases. Periodic evaluation of the hypothalamic-pituitary axis is essential to determine whether early hormonal replacement therapy is necessary. PMID- 1742886 TI - Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children. AB - OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion. PMID- 1742887 TI - Current role of magnetic resonance imaging and gadolinium enhancement in current British ENT practice. PMID- 1742888 TI - Episodic nocturnal hypoxia and nasal packs. AB - Nasal obstruction influences respiration during sleep and nasal packs may cause obstructive sleep apnoea. In order to investigate this, the perioperative oxygen saturation was monitored for 3 nights with continuous pulse oximetry in 12 patients, who had bilateral nasal packs after septoplasty. A significant increase in the number of nocturnal episodes of hypoxia and a significant prolongation of the mean duration of the individual hypoxic periods were demonstrated during the first and the second post-operative nights. The clinical significance of these results is as yet unknown, but the use of partial nasal packing in septoplasty is advocated. Further investigations of nocturnal oxygen desaturation and design of nasal packs, securing the post-operative nasal airway, are needed. PMID- 1742889 TI - Late results of laterofixation in the treatment of bilateral abductor paralysis of the vocal cords: a clinical study with long-term follow-up. AB - Thirty-four patients with bilateral vocal cord abductor paralysis were treated surgically during the period from 1960 to 1979. The main cause of paralysis was thyroid surgery (85%). Woodman's external laterofixation was performed in 31 patients, 1 had laterofixation by laryngofissure and 2 had endoscopic arytenoidectomy. In Woodman's procedure the body of the arytenoid cartilage was removed in 10 cases and mobilized from the cricoarytenoid joint in 21 cases. Thirteen of the 34 patients needed further surgery. Including previously performed procedures in 6 patients, altogether 68 operations were performed and 17 patients (50%) were operated on more than once. The immediate failure rate of laterofixation was 22% but the need for reoperation increased with time and the total failure rate of the method was 44%. Endoscopic arytenoidectomy was successful in 1 of 2 cases as a primary operation and in 3 of 3 cases as secondary operation. Follow-up time ranged from 2 months to 29 years 8 months (mean 15 years 10 months). PMID- 1742890 TI - Oesophageal speech after laryngectomy: a study of possible influencing factors. AB - 52 patients with laryngeal carcinoma were studied before and after laryngectomy with regard to what factors might influence the development of oesophageal speech. The investigations consisted of oesophageal manometry, a follow-up interview and a review of surgical approaches and radiotherapy. 43% of the patients achieved socially acceptable oesophageal speech, 22% were able to speak single words, and 35% had no oesophageal speech at all. 61% had post-operative dysphagia. Age was the only factor which significantly correlated to intelligible speech. The intraoesophageal pressure during oesophageal phonation exceeded in all cases the low PO-HPZ pressure after operation. The extension of surgery and radiation field, severity of dysphagia, alcohol and smoking habits, and mental condition did not differ between the 3 groups of oesophageal speech. It was concluded that the rather complicated process of acquiring oesophageal speech is much more dependent on learning ability which decreases with age than on various kinds of motor dysfunction after laryngectomy. PMID- 1742891 TI - The prevalence of psychological disturbance in neurotology outpatients. AB - This study assesses the prevalence of psychological disturbance among a consecutive series of 120 neuro-otology outpatients, using a structured interview conducted by a clinical psychologist. 42% of all patients were found to be in need of, and were offered, psychological help (27% of those with hearing loss, 45% of those with tinnitus and 64% of those with dizziness). 86% of those offered psychological help accepted it. Current psychological distress was associated with the number of symptoms complained of and past psychiatric history. Patients completed the General Health Questionnaire which was found to have a sensitivity rate of 82% and a specificity rate of 87% in this setting. Physicians were also asked to rate patients' psychological state; close agreement was found between these ratings and those of a psychologist. The contribution of psychological assessment of neuro-otology patients is discussed. PMID- 1742892 TI - Aspirating middle ear effusions when inserting ventilation tubes: does it influence post-operative otorrhoea, tube obstruction or the development of tympanosclerosis? AB - This prospective study examined the influence of aspirating middle ear effusions, immediately prior to ventilation tube insertion, upon the subsequent development of otorrhoea and tympanosclerosis. 50 children were studied and aspiration of effusions did not influence the incidence of purulent otorrhoea or ventilation tube obstruction within 1 month of surgery. The development of tympanosclerosis did not correlate with effusion aspiration, but in those ears which had an effusion aspirated there was a relation between operative bleeding and the development of tympanosclerosis. PMID- 1742893 TI - Squamous carcinoma of the posterior pharyngeal wall. AB - We present 70 patients with tumours of the posterior pharyngeal wall, considering tumours of the posterior hypopharyngeal and posterior oropharyngeal wall as one unit. Almost half (45%) of the patients were in poor general condition at the time of presentation, and 60% had Stage III or IV tumours. One-third of the patients were untreated, and surgery was mainly reserved for patients with Stage I and II tumours. The larynx could be preserved in two-thirds of those undergoing surgery. The best current method of repair of the posterior pharyngeal wall after partial pharyngectomy appears to be a revascularized radial forearm flap. The median survival for patients with Stage I tumours was 236 weeks, but for patients with Stages II-IV tumours was only 33 weeks. There was no significant difference between the survival for II-IV stage groups, but there was between Group I and the rest. We identify 2 defects in the UICC classification system: lack of definition of the lateral limit of the posterior pharyngeal wall, and a gross discrepancy between size and T staging of tumours arising primarily from the posterior wall of the hypopharynx. PMID- 1742894 TI - Expression of epidermal growth factor receptor in glottic carcinoma and its relation to recurrence after radiotherapy. AB - The expression of EGFR was determined immunohistochemically in two groups of patients with glottic carcinoma, one that recurred after a full course of radiotherapy and one that did not. Using a 4-graded scale (-,+,++, ) 80% (12/15) of the recurrent carcinomas had a staining intensity and proportion of stained cells of ++ or more. The same figure for non-recurrent carcinomas was 39% (7/18). The difference is statistically significant (chi-squared with Yates' correction, P less than 0.05). The results indicate that an increased expression of EGFR may influence the rate of recurrence of glottic squamous cell carcinoma after radiotherapy. PMID- 1742895 TI - Rehabilitation of facial nerve palsy. AB - Forty-nine patients underwent 158 procedures (including 19 revisions) for complete facial palsy. The variety of causes of facial palsy are enumerated, with the various procedures used to rehabilitate the face. Some improvement is invariably achieved. It is concluded that a readiness to intervene with a wide choice of procedures as early as realistically possible offers the best outcome in function and cosmetic appearance. PMID- 1742896 TI - Ossicular geometry and the choice of technique for ossiculoplasty. AB - The dimensions of the space between the handle of the malleus and the plane of the head of the stapes have been investigated in 31 preserved temporal bones and 20 patients with defects of the incus. The width (A) and depth (B) were measured directly and other dimensions were then calculated. In the preserved temporal bones A varied between 0.5 and 3 mm (mean 2.0 mm), while for the patients the range was 1.5-3.8 mm (mean 2.2 mm). The dimension B varied between 1 and 2.5 mm (mean 1.7 mm) in the temporal bones and between 0 and 2 mm in the patients (mean 0.9 mm). This difference is statistically significant (P less than 0.0001). The angle at which a graft placed directly between the stapes head and malleus handle would lie relative to the long axis of the stapes varied between 14 degrees and 71 degrees in the temporal bones (mean 49 degrees) and between 0 degrees and 79 degrees in the patients (mean 63 degrees). This difference is also statistically significant (P less than 0.001). These differences may be due to chronic Eustachian tube dysfunction or to a tendency of the malleus to become displaced medially when it is not supported by the incus/stapes complex. These findings have significant implications for the mechanical properties of different methods of ossiculoplasty, and the relative position of the malleus and stapes should be taken into account when choosing the technique to be used in an individual case. PMID- 1742897 TI - A study of the complications of grommet insertion for secretory otitis media in the presence of nasopharyngeal carcinoma. AB - Accepted treatment of secretory otitis media, in the presence of nasopharyngeal carcinoma treated with radiotherapy, includes the insertion of a grommet. This study analyses the incidence of otorrhoea following this treatment as compared to a control group. Results show that persistent otorrhoea occurred frequently (68%) in the study group and was refractory to antibiotic therapy. Alternative methods of management of the secretory otitis, such as a hearing aid, should be considered to avoid the complications of grommet insertion in this group of patients. PMID- 1742898 TI - The effect of glycerol on the guinea-pig hydropic ear. AB - The aim of this paper was to investigate the effect of glycerol on experimental endolymphatic hydrops in guinea-pigs. The right endolymphatic sac and duct were obliterated through an extradural posterior fossa approach. Some animals received a 3 g/kg dose of glycerol for a period of 7 days, whereas others received the same dose for 30 days. The activity of glycerol was studied by investigating the volumetric changes in the scala media determined with a computerized planimeter. Glycerol induced a significant reduction of the hydrops showing its effectiveness and suggesting a strial metabolic response. PMID- 1742899 TI - Audit of stapedectomy results in a teaching hospital. AB - The number of stapedectomies performed annually has declined since 1963. Also, surgery has become available at an increasing number of centres, resulting in a further fall in the number of such operations performed in teaching hospitals. Several studies have suggested benefit might be gained, both by patients and by otology as a speciality, from limiting training to post-graduates who show an aptitude for otology, and concentrating surgery in a small number of specialized centres. We report a series of 179 patients who had stapedectomy performed for otosclerosis in a teaching hospital. We have retrospectively compared the audiological outcome and complication rates for consultants and surgical trainees. For the two groups, there is no significant difference in postoperative hearing levels and complication rates are similar. Our success rate is comparable to other major series. We conclude that stapedectomy is a safe procedure to teach adequately experienced and supervised trainees. PMID- 1742900 TI - The nature of the epithelium in acquired cholesteatoma. Part 2. Cell culture. AB - The exact nature and role of the epithelial layer in cholesteatoma remains undetermined. The aim of this study was to investigate cholesteatoma epithelium and normal aural epithelia in common cell culture conditions. Samples of cholesteatoma, external meatal epidermis and middle ear mucosa were obtained, successfully grown in cell culture, and subcultured. No significant morphological differences were found between cholesteatoma and aural epidermis. The only differences noted were delayed onset of colony formation, and the need to subculture prior to the cultures becoming confluent in the cholesteatoma cultures. Further research is required to account for these differences in growth patterns. PMID- 1742901 TI - Treatment of recurrent acute tonsillitis with clindamycin. An alternative to tonsillectomy? AB - The failure of treatment with penicillin in patients suffering from acute beta haemolytic streptococcus Group A tonsillitis, may be due to the presence of beta lactamase-producing bacteria. Several studies indicate that treatment with clindamycin may prevent recurrence and thereby eliminate the need for tonsillectomy. In this prospective study, 54 patients with recurrent acute tonsillitis were investigated. 29 patients were treated with clindamycin, 150 mg 4 times daily for 10 days, while 25 patients received no antibiotic treatment and served as a control group. A significantly reduced number of episodes of acute tonsillitis (P less than 0.01) and of tonsillectomy (P less than 0.001) was found in the group of patients treated with clindamycin. PMID- 1742902 TI - The effect of early blood transfusion on severe epistaxis. AB - This retrospective study assesses the effect of early blood transfusion on the subsequent progress of patients admitted with severe epistaxis. Both further bleeding and surgical procedures were more frequent in those receiving blood within the initial 24 h. It was concluded that the need for early blood transfusion should be assessed with care. PMID- 1742903 TI - Sleep nasendoscopy: a technique of assessment in snoring and obstructive sleep apnoea. AB - It appears that uvulopalatopharyngoplasty (UVPP) is a reliable procedure for reducing snoring, but much less reliable when used as a treatment for OSAS. This is thought to be because of poor patient selection in that the site of the problem is not always the site of the operation. We present the technique of sleep nasendoscopy which allows direct visualization of the site or sites of obstruction in a sleeping patient. Our study has shown that there are patients with obstructive sleep apnoea syndrome (OSAS) in whom the only site of pharyngeal obstruction is at the velopharynx. These patients should do well with the relatively simple procedure of UVPP. This is not true for many other OSAS patients in whom we found that obstruction was multisegmental. This helps to explain the frequently poor results of UVPP in OSAS patients. We feel that this form of preoperative assessment will avoid unnecessary surgery. PMID- 1742904 TI - The stunned and hibernating myocardium: a brief review. AB - DEFINITIONS: Stunned myocardium is viable myocardium salvaged by coronary reperfusion that exhibits prolonged postischemic dysfunction after reperfusion. Hibernating myocardium is ischemic myocardium supplied by a narrowed coronary artery in which ischemic cells remain viable but contraction is chronically depressed. CLINICAL EVIDENCE: Stunned myocardium has been identified in the following patient groups: (1) thrombolysis or percutaneous transluminal coronary angiography (PTCA) in patients with acute evolving infarction; (2) unstable angina; (3) exercise-induced angina; (4) coronary artery spasm; (5) platelet aggregation or transient thrombosis of a coronary artery; (6) PTCA for chronic myocardial ischemia; and (7) immediately following coronary artery bypass graft (CABG). Evidence of hibernating myocardium (LV dysfunction) is found in the patient with severe coronary artery stenosis, even in asymptomatic patients at rest. Stunned myocardium returns to normal after a prolonged period of time (hours to weeks). Hibernating myocardium returns to normal function rather quickly if the cause is removed. DIFFERENTIATION: Stunned myocardium can be differentiated from hibernating myocardium by three clinical parameters, namely, LV wall motion, myocardial perfusion, and myocardial metabolism. Stunned myocardium has abnormal wall motion that tends to normalize in response to inotropes and postextrasystolic potentiation. Perfusion is adequate and metabolism is also adequate. Hibernating myocardium also has abnormal wall motion, which normalizes after nitrates, inotropes, post extrasystolic potentiation (PESP), PTCA, or CABG. Myocardial perfusion is reduced but can be reversed with PTCA or CABG and metabolism is adequate. PMID- 1742905 TI - Influence of minimal angiographic visible collateral circulation on myocardial function during PTCA. AB - The potential protective role of angiographically visible minimal collateral circulation in diagnostic angiograms, not reaching or filling the target vessel (RENTROP class 1), on myocardial function during percutaneous transluminal coronary angioplasty (PTCA), was studied in two groups of patients undergoing elective PTCA of the left anterior descending artery (LAD). In the first study group consisting of 22 patients, influence of collateral circulation class 1 on left ventricular regional function was evaluated. In this group, 14 patients showed no angiographic collaterals and 8 patients showed collateral circulation class 1 in diagnostic angiograms. Increase of end-diastolic and end-systolic volume indices as well as decrease of global left ventricular function was not significantly different inpatients with and without such minimal collateral circulation. In patients without collaterals, the decrease of regional left ventricular function was significantly more pronounced in the left anterior length segment (p less than 0.05) and a trend was observed in the anterolateral (p = 0.059) and apical (p = 0.053) segments. In a second group, consisting of 29 patients, hemodynamic parameters were measured and, in addition to grading of collateral circulation in diagnostic angiograms, angiographically visible collateral circulation was estimated during occlusion of the LAD by injecting contrast materials into the right coronary artery. An increase of angiographically visible collaterals during the ischemic period of various degrees was documented in 26 (90%) of 29 patients. Combining patients of both study groups, increase in left ventricular end-diastolic pressure during ischemia was significantly higher (p less than 0.05) in patients without collaterals on diagnostic angiography (n = 34) than in patients with collateral circulation class 1 (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742906 TI - Relationship between electrocardiographic patterns and angiographic features in isolated left circumflex coronary artery disease. AB - The relation of electrocardiographic (ECG) patterns to clinical and angiographic features was assessed in 89 patients with isolated left circumflex coronary artery (LCx) disease (46 with and 43 without myocardial infarction). ECG abnormalities were present in 75 patients; there were isolated Q waves in 20, an abnormal R wave in lead V1 with or without inferior and/or lateral Q waves in 21, and isolated ST-T wave changes in 34 cases. Inferior abnormalities on the electrocardiogram were similar in patients with proximal or distal stenoses of the LCx, but an abnormal R wave in lead V1 correlated with proximal LCx stenosis (p less than 0.01). Lateral abnormalities were more common in stenoses of the obtuse marginal branch and proximal LCx than in distal stenosis (all p less than 0.01). Compared with patients without myocardial infarction with or without ST-T wave changes and those with infarction without an abnormal R wave in lead V1, patients with LCx-related infarction and an abnormal R wave in lead V1 associated with inferior and/or lateral Q waves had larger left ventricular end-diastolic and end-systolic volumes, lower ejection fraction, higher incidence of total occlusion of proximal LCx without collateral vessels, and more cardiac events during follow-up. This study suggests that an abnormal R wave in lead V1 associated with lateral abnormalities on the standard electrocardiogram may be clinically useful in predicting proximal LCx stenosis and identifying a subset of postinfarction patients with left ventricular dysfunction due to a large infarct size. PMID- 1742907 TI - Elevation of factor VII activity and mass in coronary artery disease of varying severity. AB - The present study was undertaken to determine whether the extent of Factor VII elevation correlated with the severity of coronary artery disease and whether zymogen or activated Factor VII was responsible for this elevation. A group of 69 patients with coronary artery disease with old myocardial infarction was compared with 28 control subjects. The patient groups showed elevated levels of Factor VII procoagulant activity (FVII:C) and more markedly elevated Factor VII antigen (FVII:Ag) levels than the control group; therefore they had a decreased FVII:C to FVII:Ag ratio. The increased Factor VII level in the patient groups was caused by elevated Factor VII zymogen levels, and not by activated Factor VII. Since FVII:C levels strongly correlated with the titer of thrombin-antithrombin III complexes in all patients, the hypercoagulable state accompanying severe coronary atherosclerosis seems to underlie the increase of FVII and TAT in the stable phase of myocardial infarction. PMID- 1742908 TI - Diastolic pressure-volume relationship during handgrip exercise in patients with coronary artery disease. AB - There is some controversy regarding the mechanisms of an upward shift in the left ventricular diastolic pressure-volume curve during ischemia. The effects of handgrip exercise on the pressure-volume curve were examined in 21 patients with coronary artery disease and in 6 control subjects. Pressure-volume curves were constructed from digitized left ventricular pressure and volume derived from biplane left ventriculogram. Diastolic pressure-volume curve shifted upward in 12 patients with coronary artery disease during handgrip exercise (Group 1), but not in the other 9 patients who were similarly afflicted (Group 2). The upward shift did not occur in any control subject. No difference was observed in rate-pressure product gain during exercise. In Group 1, left ventricular end-diastolic pressure increased (p less than 0.01) and ejection fraction was reduced (p less than 0.01), although it did not change in Group 2. In Group 1, the time constant was prolonged (p less than 0.01) with no change in the coefficient for elastic modulus. In Group 2, these parameters remained unchanged. Group 1 was accompanied by more extensive asynergy than Group 2. Thus, isometric handgrip exercise resulted in an upward shift in the diastolic pressure-volume curve in patients with coronary artery disease. Incomplete relaxation and/or the viscoelastic properties of the left ventricle associated with ischemia could be responsible for this phenomenon. PMID- 1742909 TI - Exercise performance and beta-adrenergic blockade in patients with complete heart block treated with ventricular inhibited pacing. AB - The effect of beta-adrenergic blockade (propranolol) on exercise performance was studied in 15 patients (12 men and 3 women, mean age 70 years) with complete heart block treated with a ventricular-inhibited pacemaker (VVI). In a double blind procedure, the patients were randomly given either 0.1 mg/kg of propranolol or saline solution i.v. before a first exercise test and vice versa before a second test. The interval between the tests was 24 hours. Nine patients were in sinus rhythm, 4 patients had atrial flutter, and 2 others had atrial fibrillation. The exercise capacity was on an average 11% lower with propranolol than with placebo (p less than 0.001). The most marked reductions (20 and 33%) were found in the two patients with atrial fibrillation. The atrial rate in patients with sinus rhythm was significantly lower with propranolol than placebo both at rest (68 vs. 83 beats/min, p less than 0.001) and at maximal work load (91 vs. 141 beats/min, p less than 0.001). The present findings show that beta blockade has negative effects on exercise capacity in patients with complete heart block treated with VVI pacemakers. This finding should be considered in the selection of drug treatment in patients with fixed rate pacing and concomitant hypertension and/or ischemic heart disease. PMID- 1742910 TI - Catheter balloon valvuloplasty of stenotic porcine bioprosthetic valves: Part II: Mechanisms, complications, and recommendations for clinical use. AB - During the last several years dilating balloons have been applied in the treatment of stenotic cardiac valves. This interest has been extended to stenotic porcine bioprosthetic valves. Part I of this review discusses the pathologic changes producing stenotic porcine prosthetic valves. Part II of this review describes an in vitro study of porcine prosthetic valve valvuloplasty defining the mechanisms, complications, and clinical applications. Results of this study indicate a limited and cautious role in balloon dilation of stenotic bioprosthetic valves. PMID- 1742911 TI - Accelerated idioventricular rhythm detected during elective surgery in a healthy man. AB - Accelerated idioventricular rhythm (AIVR) is found most commonly in the presence of underlying heart disease. It is characterized by acceleration of a latent pacemaker that normally depolarizes slowly. We describe a 30-year-old man who was found to have episodes of accelerated idioventricular rhythm (AIVR) on cardiac monitoring during elective orthopedic surgery. Noninvasive evaluation including two-dimensional echocardiography was unremarkable. No late potentials were detected on a signal-averaged electrocardiogram. During an exercise tolerance test, AIVR was suppressed as heart rate increased. A 24-h Holter monitor revealed that the AIVR rate was consistently 73-76 beats/min, which appeared whenever the sinus rate slowed to this level. The patient has been asymptomatic, and the rhythm has persisted at least through a 5-month follow-up period. PMID- 1742912 TI - Angina pectoris due to possible vasospasm of small coronary arteries. AB - Recently, the presence of vasospasm in small coronary arteries is speculated in animals and humans. A 40-year-old female patient complained of chest pain at rest. Left ventriculogram showed normal wall motions. Left and right coronary arteries were also normal. After methylergometrine maleate was selectively administered to a right coronary artery, she complained of chest pain, and ST segment elevation was detected in leads II, III, and aVF of ECG. Right coronary arteriography was performed immediately, but no coronary stenosis was found. The next day, methylergometrine maleate was again administered intravenously and the patient complained of chest pain, but no ischemic changes were observed in ECG. Thallium-201 myocardial scintigraphy followed immediately. Apical perfusion defect was detected in stress image. In the delayed image, it showed complete redistribution. Three days later, catheterization and scintigraphy were performed at the same time. When methylergometrine maleate was administered to the left coronary artery, she complained of chest pain within a few minutes of the injection; however, ECG remained unchanged. 201Tl myocardial scintigraphy was performed immediately. In the stress image, it showed apical perfusion defect as shown in the intravenous methylergometrine maleate injection study. It also showed complete redistribution in the delayed image. Apical perfusion defect can be attributed to myocardial ischemia of left coronary artery, which are too small to be detected by conventional coronary arteriography. Vasospasm in small coronary arteries may be involved in this phenomenon. PMID- 1742913 TI - Critical noise level reduction for correct identification of late potentials: an illustrative case report. AB - The precision of detection of late potentials (LPs) on signal-averaged electrocardiography (SAECG) depends on the degree of noise reduction. The recommended low-noise endpoint is 0.3 microV. We describe a patient with sustained ventricular tachycardia after myocardial infarction with very low amplitude LPs in whom a noise level lower than 0.3 microV was necessary in order to obtain an abnormal result of the SAECG. The presence of LPs was confirmed by spectral temporal mapping of the SAECG. PMID- 1742914 TI - Cytoplasmic pH regulation in monocytes and macrophages: mechanisms and functional implications. AB - Maintenance of cytoplasmic pH (pHi) within a narrow physiological range is critical to optimal cell function. Monocytes and macrophages (Mos) actively regulate their pHi through three distinct plasma membrane ion transport systems: (1) Na+/H+ exchange; (2) Na(+)-dependent anion exchange; and (3) vacuolar-type H+ ATPases. Alterations in the functional state of monocytes and Mos have been linked to changes in pHi and/or its regulation by these ion transport systems. Differentiation, proliferation, and activation of Mos in response to a variety of agents are associated with increased Na+/H+ exchange. The resultant cytoplasmic alkalinization typically observed in HCO3(-)-free media likely plays a permissive, rather than a triggering, role in mediating Mo response to most of these agents. Prevention of cytoplasmic acidification is essential during Mo activation, when production of metabolic acid increases. This is of particular importance within the in vivo microenvironment of an abscess or tumour, where pHi is further threatened by the low extracellular pH (pHo) which typically prevails. At low pHo, H+ ATPase-mediated H+ extrusion plays a critical role in maintenance of pHi, preserving the ability of Mos to generate a respiratory burst. The requirement for maintenance of pHi within a range conducive to efficient Mo function may explain why Mos have acquired a variety of parallel systems for pHi regulation. PMID- 1742915 TI - Safety and immunogenicity of subcutaneous H. influenzae vaccines in 15-17 month old children. AB - To evaluate the safety and immunogenicity of subcutaneously administered PRP and PRP-D, one hundred and one healthy 15 to 17 month-old children were randomly assigned to receive two subcutaneous doses, 2 months apart, of either vaccine. The incidence of local and systemic reactions did not differ significantly between the two groups. PRP antibody levels in the pre-immunization sera of 95% of subjects were below the level associated with immediate protection from Hib disease (less than 0.15 microgram/ml). After the first dose, 32% of PRP and 70% of PRP-D (p less than 0.001) recipients achieved antibody levels of greater than or equal to 0.15 microgram/ml, and 8% and 26% (p = 0.003) respectively achieved levels greater than or equal to 1 microgram/ml, a level believed to predict long term protection. After the second dose, antibody levels greater than or equal to 0.15 microgram/ml were reached in 38% of PRP and 88% of PRP-D (p less than 0.001) recipients and levels of greater than or equal to 1 microgram/ml were reached in 22% and 78% respectively (p less than 0.001). The geometric mean levels of PRP antibody after immunization were significantly higher in the PRP-D group after both the first and second doses (p less than 0.001). These results suggest that subcutaneous administration of both vaccines is safe, but PRP-D results in significantly higher antibody levels compared to PRP. The levels were lower than what has been reported following intramuscular administration. PMID- 1742916 TI - Renal handling of cisplatin: interactions with organic anions and cations in the dog. AB - Cis-diamminedichloroplatinum (II) (cisplatin CDDP) is an extremely potent chemotherapeutic agent. Its efficacy, however, is hindered by the cumulative dose dependent nephrotoxicity which can lead to permanent renal impairment. The mechanisms of the renal transport of cisplatin are not clear. As a first step towards understanding the renal handling of cisplatin we studied its renal clearance in dogs, as well as the effects of organic anion and cation administration on cisplatin. Our results document net tubular secretion of cisplatin. Both an organic anion (probenecid) and cations (quinidine, cimetidine, ranitidine) significantly decreased renal clearance of free CDDP without affecting GFR. PMID- 1742917 TI - The relationship between the absolute granulocyte count, platelet count and total leukocyte count in cancer chemotherapy patients. AB - A cohort of 383 patients with a variety of malignancies receiving various chemotherapy programs was analyzed to determine the relationship between the absolute granulocyte count (AGC) and the total leukocyte count (TLC). Specific groups, who were elderly, had proven bone marrow involvement, or were receiving significant doses of prednisone, were studied. The relationship between the TLC and thrombocytopenia was also examined. Results revealed that in all groups there was a correlation between the TLC and the AGC with correlation coefficients ranging from 0.82 to 0.88. Both life-threatening thrombocytopenia and granulocytopenia were rare, providing and TLC was greater than 3.0 x 10(9)/L. PMID- 1742918 TI - Monocyte membrane ferritin in hemochromatosis. AB - To further evaluate a possible abnormality in the reticuloendothelial cells in hemochromatosis, the binding of a monoclonal anti-human liver ferritin antibody to monocytes was studied in 19 patients with hemochromatosis, 8 patients with secondary iron overload, 1 patient with hyperferritinemia without iron overload, and 15 normal volunteers. Binding of the antibody to the monocytes was analyzed using a fluorescence-activated cell sorter (FACS). Binding of the anti-ferritin antibody to monocytes was demonstrated in 34.7 +/- 4.5% (mean +/- standard error) of the monocytes in untreated hemochromatosis patients (mean serum ferritin = 2294 +/- 415 micrograms/L), 6.75 +/- 2.03% in treated hemochromatosis patients (mean serum ferritin = 263 +/- 85 micrograms/L), 12.3 +/- 2.7% of the monocytes in the secondary iron overload patients (mean serum ferritin = 2476 +/- 867 micrograms/L), 4.1% in the patient with hyperferritinemia (serum ferritin = 1192) and 4.1 +/- 0.5% of the monocytes in the normal volunteers (mean serum ferritin = 55.2 +/- 11.9 micrograms/L). % binding of anti-ferritin antibody was significantly greater in hemochromatosis patients compared to patients with secondary iron overload (p less than 0.05) despite a comparable degree of iron overload in the secondary iron overload group. The addition of exogenous human ferritin to samples from treated hemochromatosis patients and normal volunteers did not significantly increase the % of monocytes binding anti-ferritin antibody. These results suggest that monocytes from iron-loaded hemochromatosis patients express increased surface ferritin which may represent release of ferritin and a metabolic defect characteristic of hemochromatosis. PMID- 1742919 TI - Effect of intermediate-dose naloxone on cardiovascular and sympathoneural adjustments to exercise. AB - The effects of intermediate-dose naloxone on sympathetic nerve activity and cardiovascular adjustments to exercise were examined in two series of experiments. In the first series 10 normal male volunteers, mean age 28 +/- 5 (SD) years received i.v. naloxone, mean 0.28 +/- 0.6 mg/kg in 0.1 mg/kg aliquots 60-90 min after 45 min of submaximum treadmill exercise. Naloxone had no detectable effect on supine blood pressure, heart rate, plasma norepinephrine, or epinephrine concentrations or muscle sympathetic nerve burst frequency at rest or during the strain phase of the Valsalva manoeuvre, but decreased slightly sympathetic burst incidence at rest (p less than 0.05). In the second study, 8 of these subjects repeated the exercise protocol 15 to 20 min after 0.1 mg/kg i.v. naloxone. Supine blood pressure, heart rate, plasma norepinephrine and epinephrine concentrations before and 15 min after naloxone were virtually identical. A comparison of results from both study days did not reveal a naloxone effect on blood pressure during or up to 60 min after exercise, whereas the heart rate response to exercise was attenuated (p less than 0.002). Intermediate-dose naloxone has no apparent effects on blood pressure during and after exercise, attenuates the chronotropic response to exercise, and has only modest inhibitory effects on muscle sympathetic nerve activity. PMID- 1742920 TI - Dietary alterations of plasma lipoproteins influence their interactions with proteoglycan enriched extracts from neointima of normal and injured aorta of rabbit. AB - The interactions between serum lipoproteins isolated from rabbits fed a cholesterol-supplemented diet for six weeks, and soluble extracts of arterial neointima enriched in proteoglycans extracted from normocholesterolaemic rabbit aortas, were studied in an in vitro system. Neointimal tissues of rabbit aorta, which developed during three months following a selective endothelial injury, were excised and the areas covered or uncovered by regenerated endothelium were separated. To isolate the proteoglycan enriched fraction, both normal and injured tissue was homogenized in a sucrose solution containing protease inhibitors, centrifuged, and further fractionated by gel exclusion chromatography. The composition of the soluble extracts and each of their corresponding proteoglycan enriched fractions were analyzed in terms of protein and glycosaminoglycan content. Lipoproteins of donor animals fed an atherogenic diet were prepared by sequential ultracentrifugal flotation after density adjustment with KBr. Aliquots of electrophoretically pure lipoprotein fractions were incubated with proteoglycan enriched fraction from uninjured, denuded, or endothelium-covered neointima in the presence of Ca++ and Mg++ at 4 degrees C. The complexes formed during incubation were separated by centrifugation. The cholesterol content of the complexes was considered as an index of binding capacity. Results were expressed as micrograms of cholesterol bound per mg of glycosaminoglycan. The data reveal the higher affinity of hypercholesterolaemic lipoprotein fractions for aortic proteoglycans, as compared to normocholesterolaemic lipoproteins. In addition, when evaluating the relevance of the proteoglycan enriched fraction source, the affinity of fractions extracted from aortic neointima was found to be much higher for hypercholesterolaemic lipoproteins. These results suggest the role that proteoglycan-lipoprotein interactions could play in the event of the combined actions of endothelial injury and hypercholesterolaemia in the pathogenesis of atherosclerosis. PMID- 1742921 TI - The effect of human recombinant erythropoietin on iron absorption and hepatic iron in a rat model. AB - In order to ascertain whether recombinant human erythropoietin (EPO) therapy would result in further intestinal iron absorption in the setting of systemic iron loading, iron absorption was measured in iron-loaded rats receiving EPO therapy and a control group of iron-loaded rats. Parenteral iron dextran (100 mg) resulted in hepatic siderosis with predominantly a reticuloendothelial distribution. EPO was given by intraperitoneal injection (100 U/kg) for 10 days. Radioiron absorption was measured by total body counting. Iron absorption in EPO treated rats was 4.8 +/- 2.0% (n = 12) and 4.5 +/- 2.2% (n = 10) in the control rats (p greater than 0.05). Mean hemoglobin in the EPO rats was 201 +/- 12.5 g/L and 140 +/- 18.2 g/L in the control rats (p less than 0.001). Mean hepatic iron concentration was 73 +/- 16 mumol/g in the control rats and 34 +/- 9.1 mumol/g in the EPO-treated rats (p less than 0.001). This study suggests that iron-loaded rats do not demonstrate an increase in intestinal iron absorption with EPO therapy despite a significant erythropoiesis. The reduction in hepatic iron concentration suggests that reticuloendothelial iron is accessible and mobilized to produce new red blood cells. PMID- 1742922 TI - Seroprevalence and demographic characteristics of injection drugs users among individuals at risk for HIV infection in Winnipeg, Manitoba, Canada. AB - From June 1986 to March 1990, a prospective seroprevalence survey and questionnaire of individuals at risk for HIV infection was conducted with volunteers in Winnipeg. Of 610 individuals enrolled, 146 were injected drug users (IDU). Fifteen IDU were in a methadone treatment program and all were seronegative. Three of 131 remaining IDU were HIV-1 seropositive (2.3%), a rate similar to 2.2% positive (20+ of 927) in diagnostic specimens from IDU tested in the province. Demographics and behaviour of 131 IDU were compared with 335 individuals, of whom 112 were gay/bisexual [24 of whom also had sexually transmitted diseases (STD)] and 223 heterosexuals who had STD. Males enrolled were significantly older than females. Multivariate analysis showed that factors independently associated with IDU were: a younger age, less education, mental health counselling, unemployment, and a history of jaundice or hepatitis. Drugs most commonly used were Ritalin/Talwin, cocaine, and heroin. Over 90% of individuals admitted to sharing needles. In spite of the low seroprevalence of HIV-1 infections, these individuals are important for the potential spread of HIV because of multiple means of acquiring and transmitting HIV and a high rate of needle sharing. PMID- 1742923 TI - Effects of class I anti-arrhythmic drugs in infarcted tissue. AB - An in vitro model was used to examine the electrophysiological effects of anti arrhythmic drugs in infarcted tissue. After 24 h of coronary artery occlusion in the dog, endocardial preparations were removed from the infarcted zone. Intracellular action potentials recorded from surviving Purkinje fibres on the endocardial surface showed reduced maximum upstroke velocity (Vmax), increased action potential duration and enhanced automaticity. The rate-dependent effect of lidocaine on Vmax and conduction was more prominent in Purkinje fibres that survived myocardial infarction than in normal Purkinje fibres. Tocainide, flecainide, and O-demethyl encainide reduced Vmax in both normal Purkinje fibres and Purkinje fibres surviving infarction. Similar to lidocaine, these drugs showed the greatest reduction of Vmax in Purkinje fibres surviving infarction at the shortest stimulation cycle length tested. In contrast, maximal drug effects on action potential duration were observed when long stimulation cycle lengths were used. Our results indicate that most Class I anti-arrhythmic drugs showed rate-dependent properties in normal Purkinje fibres as well as in Purkinje fibres surviving infarction. The increased sensitivity of the ischemic myocardium to anti-arrhythmic drugs resulting in greater reductions of Vmax and conduction may contribute to a greater potency of anti-arrhythmic drugs in the suppression of arrhythmias associated with ischemia. Conversely, while slowing of conduction can abolish re-entry arrhythmias by producing a bidirectional block, further slowing of conduction by anti-arrhythmic drugs can favour the development of new re-entry pathways and may contribute to their pro-arrhythmic effects. PMID- 1742924 TI - Commentary on 'Links between passive smoking and disease: a best evidence synthesis--a report of the Working Group on Passive Smoking'. CIM Vol. 13, No. 1: 17-42, 1990. PMID- 1742925 TI - Papillary cancer in a patient treated with radioiodine for Graves' hyperthyroidism. Case report and a review of the risk. AB - A small encapsulated papillary thyroid cancer was found in a patient who had received I-131 therapy for Graves' disease 31 months previously. The relationship of Graves' hyperthyroidism and thyroid cancer is discussed, as well as the possible role of I-131 as a cause of the cancer. The published data do not support I-131 as an etiology. The patient is clinically well and cured of both hyperthyroidism and the cancer. PMID- 1742926 TI - Evaluation of phlegmasia cerulea dolens using radionuclide venography. AB - Phlegmasia cerulea dolens (PCD) is characterized by the presence of massive venous occlusion of the veins in an extremity, leading to ischemia and sometimes gangrene. We report a case of phlegmasia cerulea dolens that was evaluated by radionuclide venography. We report both this case and information regarding phlegmasia and therapy of PCD to promote awareness of this disorder among radiologists and nuclear medicine physicians who perform radionuclide venograms. PMID- 1742927 TI - HMPAO scintigraphy, MRI, and CT of a vascular fibrous dysplasia of the craniofacial bones. AB - The authors present the case of a child with a predominantly unilateral craniofacial fibrous dysplasia and a substantial redirection of internal carotid blood flow to the dysplastic bone. The case illustrates the advantages of using multiple imaging modalities in the evaluation of this disorder. CT showed the diagnostic findings of fibrous dysplasia and demonstrated the extent of bony involvement. MRI showed the extent and vascularity of the intradiploic fibrous mass and best demonstrated the distortion of underlying cerebral structures. Tc 99m HM-PAO brain scintigraphy demonstrated adequate ipsilateral cerebral perfusion, thereby excluding any significant cerebral "steal." PMID- 1742928 TI - Disassociation of splenic accumulation of Tc-99m MDP and radiocolloid. AB - Two cases of splenic uptake of Tc-99m MDP are presented, in which there was preserved reticuloendothelial activity (Tc-99m sulfur colloid accumulation). In addition to the literature data, data from these cases were used to show the disassociation of uptake of bone agents and radiocolloid in the spleen. Prior reports, in which both agents concentrated in the spleen, were tabulated. An updated gamut on splenic accumulation of Tc-99m MDP or analogues was given. PMID- 1742929 TI - Intraventricular photon deficiency in gated cardiac blood pool imaging due to left ventricular metastases from renal cell carcinoma. AB - Cardiac metastasis can occur with any widely disseminated malignancy, especially from carcinoma of the kidney, stomach, lung, breast, or from melanocarcinoma. Metastasis to the myocardium can protrude from the endocardium into the intraventricular cavity of the left ventricle. We present a case of renal cell carcinoma and left ventricle cavitary metastases, documented by an echocardiogram demonstrated in a cardiac blood pool study as a photon-deficient area in the left ventricle cavity. PMID- 1742930 TI - Iatrogenic obstructive jaundice caused by the balloon of a Foley catheter. Case report. AB - A rare kind of obstructive jaundice caused by compression on the common bile duct due to an inflated Foley catheter balloon placed in the duodenum after Suguira surgery for bleeding esophageal vesicles secondary to portal hypertension is presented. After deflating the balloon, the obstruction was relieved. Tc-99m HIDA studies were helpful in the diagnosis of obstruction of the common bile duct and the response following the deflation. PMID- 1742931 TI - Reversible functional asplenia in systemic lupus erythematosus. AB - A 44-year-old woman with a history of systemic lupus erythematosus on no steroid or immunosuppressive medication presented in septic shock complicated by renal failure and disseminated intravascular coagulation. The patient was treated with antibiotics. Liver-spleen scintigraphy with Tc-99m albumin colloid initially failed to reveal tracer accumulation in the spleen. Follow-up study after one year revealed normal tracer uptake in the spleen. The transient blockade of reticuloendothelial system by immune complexes is the most likely mechanism. Other possible mechanisms include disturbed vascular supply due to thrombosis secondary to the disseminated intravascular coagulation or vasculitis. PMID- 1742932 TI - Prediction of radionuclide bone imaging findings by Gleason histologic grading of prostate carcinoma. AB - To evaluate a relationship between Gleason scores and Tc-99m HMDP bone imaging findings, data from 48 men (aged 45 to 77; mean, 67) with prostate carcinoma who had a bone imaging study at the time of presentation were reviewed. Cumulative Gleason scores were divided into two groups: high scores (6-10), 32 men; low scores (2-5), 16 men. Of the 32 men with high Gleason scores, 15 tested positive for multiple metastases and 17 tested negative. Tumors of the 16 men with low Gleason scores were negative for metastasis. A chi-square association between Gleason scores and the presence of metastases, either of a superscan pattern or multiple metastases, was 10.9 (1 df, P less than 0.001). The results indicate that a superscan pattern or multiple metastases were found exclusively in the bone images of patients with high histologic grades; bone images negative for metastases were associated with low-grade tumors. We conclude that positive bone imaging for metastases at the initial scan occurs only in patients who have high Gleason scores, that patients with high Gleason scores might or might not have skeletal metastasis, and that skeletal metastasis is not predictable in patients with low Gleason scores. PMID- 1742933 TI - Massive tricuspid regurgitation identified on renal flow scintigraphy. AB - A Tc-99m glucoheptonate renal flow study performed in a patient with chronic renal insufficiency and worsening congestive heart failure demonstrated evidence of massive tricuspid regurgitation, with activity appearing in a markedly dilated inferior vena cava within 4 seconds of the tracer bolus entering the right ventricle. Autopsy subsequently confirmed the scintigraphic findings, demonstrating an incompetent tricuspid valve secondary to immobilization of the posterior leaflet as a result of adhesions from a longstanding right ventricular pacemaker wire. PMID- 1742934 TI - Scintigraphic distribution of Pneumocystis carinii pneumonia in AIDS treated with prophylactic inhaled pentamidine. PMID- 1742935 TI - Scintigraphic evaluation of a patient with enterocutaneous fistulas using Tc-99m latex particles. PMID- 1742936 TI - Scintigraphic findings in angiosarcoma of the skull. PMID- 1742937 TI - Unsuspected finding on a gastric emptying study. PMID- 1742938 TI - The uterine blush on In-111 labeled leukocyte scintigraphy. PMID- 1742939 TI - Sternoclavicular pyarthrosis demonstrated on bone scan. Correlation with CT and MRI. PMID- 1742940 TI - The "yarmulke' sign of Paget's disease. PMID- 1742941 TI - Further studies on acid phosphatase in obese subjects. AB - Low activity genetic variants of acid phosphatase (ACP1) are positively associated with extreme body mass deviations in obese subjects. The same pattern has been found in non-diabetic children, in diabetic pregnant women, and in non diabetic adult subjects. Low activity variants of ACP1 also show a positive association with family history of obesity, supporting the hypothesis of an enhancing action of these variants on expressivity of obesity. PMID- 1742942 TI - HLA antigen frequencies in children born to HIV-infected mothers. AB - Tissue-typing for HLA-A, B, and DR antigens was carried out on 53 babies, 47 of them unrelated, born to mothers known to be HIV-infected from intravenous drug usage or sexual contact with drug users. These babies were followed up to assess whether HLA phenotype was associated with vertical transmission of HIV infection or disease progression. Of the 47 unrelated babies, eight became infected with HIV. The frequency of HLA-DR3 was three times higher in the HIV-positive infants compared to the HIV-negative infants (43 per cent vs 15 per cent) in our study population. Conversely, HLA-A3 was three times less common in the HIV-positive infants (12.5 per cent vs 42 per cent). A comparison of HLA antigens between our study group babies and babies born to healthy mothers unselected for HIV status revealed higher proportions of HLA-B18, B7, and DR2 in the study group. Moreover, the combination, A3, B7, DR2 was four times commoner in our study population relative to controls (RR = 3.9; p less than 0.003), but was found only in babies who were not HIV infected. The combination A1, B8, DR3, in contrast, was found less often than expected in our study group (RR = 0.39) and was disproportionately represented amongst the infected babies. We have observed an unexpectedly low (6 per cent) mother-to-infant transmission rate of HIV among prospectively studied intravenous drug users. We speculate that the unusually high ratio of the common antigen combinations (often halotypes), A3, B7, DR2 to A1, B8, DR3 in this population may be contributory. PMID- 1742943 TI - Interactive effect of HLA and Gm and genetic heterogeneity tested in 79 rheumatoid arthritis families. AB - The hypothesis that there is an interactive effect between HLA and Gm genes in rheumatoid arthritis (RA) was tested in a sample of 79 RA families. An analysis, of the joint segregation of these two markers in RA sibpairs, confirmed the previously described effect of HLA in RA but did not provide evidence of an independent effect of Gm alone or in interaction with HLA. The additional hypothesis that the previously described correlation between RA and autoimmune thyroid disease is due to genetic factors, was also investigated in relation to HLA and Gm. Therefore, we examined the segregation of HLA and Gm in RA sibships depending on the presence or the absence of autoimmune thyroid disorder. This analysis showed significant heterogeneity in HLA segregation (P = 0.02) with an HLA effect restricted only to sibships without thyroid disease. There was no evidence that thyroid disease influenced Gm segregation (P = 0.19). The effect of thyroid disease on HLA segregation suggests that the familial association between RA and autoimmune thyroid disease is at least partially due to genetic factors. PMID- 1742944 TI - Interaction of immunoglobulin allotypes (Gm and Km), HLA, and sex in insulin dependent (type 1) diabetes. PMID- 1742945 TI - Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. PMID- 1742946 TI - HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. PMID- 1742947 TI - Induction of CD8+ cytotoxic T-cells by immunization with purified HIV-1 envelope protein in ISCOMs. PMID- 1742949 TI - HIV-1 infection of normal human macrophage cultures: implication for silent infection. PMID- 1742948 TI - Genetic organization of a chimpanzee lentivirus related to HIV-1. PMID- 1742950 TI - Growth and metabolism of Pneumocystis carinii in axenic culture. PMID- 1742951 TI - Direct and cytokine-mediated activation of protein kinase C induces human immunodeficiency virus expression in chronically infected promonocytic cells. PMID- 1742952 TI - High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type-I isolates. PMID- 1742953 TI - Fragments of the HIV-Tat protein specifically bind TAR RNA. PMID- 1742954 TI - The effect of interleukin 4 (BSF-1) on infection of peripheral blood monocyte derived macrophages with HIV-1. PMID- 1742955 TI - The nucleocapsid protein isolated for HIV-1 particles binds zinc and forms retroviral-type zinc fingers. PMID- 1742956 TI - Characterization of a monoclonal antibody with CD44 like reactivity. AB - QE7.3E8 is a monoclonal antibody which precipitates two bands (90 and 160 kd) from a B cell line and four (90, 130, 146, and 160 kd) from monocytes. Whilst this immunoprecipitation pattern suggests that QE7.3E8 is a CD18 antibody, a number of other results are inconsistent with this interpretation. In particular, QE7.3E8 stains lymphoid tissue with a distribution clearly distinguishable from CD18 antibodies; it precipitates four bands from a T cell line which does not express the CD11b and CD11c alpha chains, and cross immunoprecipitation with QE7.3E8 and a CD11a antibody show that the molecules recognized by these antibodies are not associated. However, in tissue distribution and sequential precipitation experiments QE7.3E8 behaves like a CD44 antibody. CD44 identifies a single 85 kd protein, but high molecular weight complexes have been described, accounting for the multiple bands seen in immunoprecipitation studies. Sequential immunoprecipitation using QE7.3E8 and a Workshop-clustered monoclonal antibody (SBU 25-32) indicate that the QE7.3E8 reacts with the CD44 antigen. PMID- 1742957 TI - Benazepril approved for treatment of hypertension. PMID- 1742958 TI - Treatment options for a patient with osteoarthritis and a history of ulcer disease. PMID- 1742959 TI - Hyperthyroidism associated with mercury poisoning. PMID- 1742960 TI - Ethnicity and clozapine-induced agranulocytosis. PMID- 1742961 TI - Management of postoperative pain by continuous epidural infusion of analgesics. AB - The anatomy and physiology of the epidural space and the mechanism of action, sites of action, and pharmacokinetics of analgesics administered by continuous epidural infusion are reviewed, and the efficacy, adverse effects, and postoperative indications for use of analgesics administered by this route are discussed. Narcotics selectively block pain conduction by occupying specific opiate receptors in the spinal cord. Local anesthetics provide analgesia by axonal membrane blockade; they also can produce nonselective sympathetic and somatic (sensory and motor) blockade in addition to analgesia. A narcotic-local anesthetic mixture should provide an additive analgesic effect, without an increase in the incidence of adverse effects. Comparative efficacy studies have shown that continuous epidural infusions of narcotics, local anesthetics, and narcotic-local anesthetic combinations, when used appropriately, may produce better analgesia than conventional bolus methods of pain relief. Continuous epidural infusions also offer a safety advantage over intermittent epidural injections because peak and trough levels of the analgesic agent are avoided. Adverse effects of epidurally administered narcotics include respiratory depression, pruritus, urinary retention, nausea and vomiting, and sedation. Adverse effects of epidurally administered local anesthetics include urinary retention, hypotension, numbness, motor weakness, tachyphylaxis, and, rarely, systemic toxicity. The cost of epidurally administered drugs is substantially higher than that for i.m. or i.v. narcotic analgesia, but this cost may be offset by other benefits such as a shorter hospital stay. Current studies suggest superior analgesia for the majority of surgical procedures with continuous epidural analgesia infusions compared with more traditional methods of providing analgesia. PMID- 1742962 TI - Treatment of chronic iron overload. AB - The clinical features and therapy of chronic iron overload are reviewed. Chronic iron overload is classified as primary or secondary hemochromatosis. In primary hemochromatosis a genetic defect in iron metabolism results in increased absorption of iron from the gastrointestinal tract. The excess iron in secondary hemochromatosis may be derived from increased gastrointestinal absorption due to ineffective erythropoiesis or from medicinal, dietary, or transfusional sources. Phlebotomy is the treatment of choice in patients with primary hemochromatosis. Iron chelation therapy is indicated in patients who are not candidates for phlebotomy. Deferoxamine mesylate, the only commercially available iron chelator, is usually administered subcutaneously or intravenously over 10-12 hours/day. Serum ferritin concentrations are measured every three to six months to monitor the effectiveness of therapy. The adverse effects of deferoxamine include local skin reactions, ototoxicity, cataracts, growth impairment, and increased susceptibility to infectious organisms. Patient compliance may be compromised by the routes of administration and cost of deferoxamine. Early detection and prompt treatment are necessary to prevent organ damage. Phlebotomy and iron chelation therapy are effective in the treatment of chronic iron overload. PMID- 1742963 TI - Altered aminoglycoside volume of distribution in patients with acquired immunodeficiency syndrome. PMID- 1742964 TI - Disorders of the testes. PMID- 1742965 TI - Current diagnosis and management of impotence. PMID- 1742966 TI - Antibodies as predictors of type 1 diabetes. PMID- 1742967 TI - Acromegaly: etiology, diagnosis and management. PMID- 1742968 TI - Menopause medicine: current treatment options and trends. AB - Demographic trends and increasing demand, as well as the intricacy of the emerging field of menopause medicine, dictates the need for a multidisciplinary approach for the care of the peri- and postmenopausal patient. A menopausal program benefits the individual patient by obviating the acute symptoms and by preventing long-term consequences. As morbidity and mortality rates associated with the long-term implications are reduced, substantial public health aspects are also beneficially affected. Cost effectiveness of a menopause program and routine HRT should be calculated as the net present value (NPV) for the health care financing program, and should prove to be greater than the NPV of future costs anticipated without an investment in primary preventive menopause program. We believe that the educated use of a menopause counseling program will yield an increasing benefit for the individual patient and the community. Should menopause be regarded as an endocrinopathy, thus justifying routine HRT, or are we engaged in the "medicalization" of a physiologic process? Bearing in mind the data reviewed above, it seems to us that ample reason exists to make every woman aware of the opportunity to receive long-term HRT. The decision to use it depends heavily on the patient's own informed assessment of her particular benefit-risk equation. Combined-continuous estrogen-gestagen replacement seems to provide the desired multisystem beneficial effects, and at the same time be the most convenient and associated with the least short-term side effects. Although emerging trends regarding the long-term risks associated with the use of such regimes are reassuring, more information needs to be elaborated before final conclusions can be offered. PMID- 1742969 TI - Diabetic ketoacidosis: etiology, pathophysiology and treatment. PMID- 1742970 TI - Diabetes in pregnancy: rationale and guidelines for care. AB - The management of pregnancy in a woman with diabetes is directed toward insuring a normal outcome for the mother and her newborn baby. There is ample evidence from studies in both humans and animals that maintenance of a normal maternal metabolic environment, particularly blood glucose concentrations, can avoid or ameliorate the complications of pregnancy responsible for increased morbidity and mortality in the mother and her baby. It is essential that this metabolic normalcy be achieved preconceptionally if congenital malformations, the leading cause of death in IDMs, are to be avoided. Thus, preconceptional care, intensive regulation of maternal glucose metabolism and fetal surveillance throughout pregnancy are critical. The use of the multidisciplinary team to optimize care has led to significant reductions in maternal and perinatal morbidity/mortality in IDMs, and is thus essential to successful outcomes in pregnancies complicated by diabetes. PMID- 1742971 TI - Diagnosis and treatment of thyroid disease in infants. PMID- 1742972 TI - Management of diabetes in the elderly. PMID- 1742973 TI - Diagnosis and treatment of osteoporosis. PMID- 1742974 TI - Assessment of instability and gait in elderly persons. PMID- 1742975 TI - Hearing loss in the elderly: causes, impact and treatment. PMID- 1742976 TI - Thiazide diuretic agents and prevention of hip fracture. PMID- 1742977 TI - Depression in the elderly. AB - Depression in the elderly can be difficult to diagnose but often responds well to treatment. In treating late-life depression, we have the satisfaction not only of relieving our patients' distress but very likely of prolonging their lives as well. PMID- 1742978 TI - Effects of aging process on digestive functions. PMID- 1742979 TI - Principles of pain management in older people. AB - The management of chronic pain should be a priority in geriatric care. Pain is a common problem that has tremendous potential to influence the physical function and quality of life of elderly people during their remaining years. Much research and education is still needed to further our understanding of pain and its management among elderly people. Existing pain management strategies should be tailored for the special needs of the geriatric population. Applications of "high tech" pain management strategies, such as morphine pumps and chronic spinal infusions, need to be clarified for older people. Finally, family and caregiver considerations should be included in chronic pain management strategies. PMID- 1742980 TI - The aging skin. PMID- 1742981 TI - Advances in clinical research in Alzheimer's disease. AB - There has been an explosion of clinical research on Alzheimer's disease (AD) in recent years, shedding light on many aspects of the disease. These include the differentiation of AD from normal aging, appreciation of genetic aspects of the disease, characterization of its pathology and pathophysiology, and the beginnings of a rational approach to treatment. Alzheimer's disease (AD) is a clinicopathologic diagnosis. In the near future, it may be possible to confirm the clinical diagnosis by examination of spinal fluid or by skin biopsy, but the diagnosis of AD in 1991 is based on history, direct examination of the patient and, ultimately, confirmation by microscopic examination of the brain. In short, we stand very close to where Dr. Alzheimer stood when he reported a hitherto unrecognized form of dementing illness in a 51-year-old woman. Alzheimer's case was cited by the editor of the journal in which it was published as an example of the need to look closely at patients from both clinical and pathologic perspectives so that individual diseases might eventually be separated out from syndromes such as dementia. Since Alzheimer's report, many clinical studies have shed further light on this disease. Two important deterrents to Alzheimer's disease research were the presumption that dementia is either a normal age related phenomenon or a psychotic disorder of old age. The assumption that dementia is a product of normal aging or a functional psychotic disorder of late life was first challenged by Corsellis, who found a strong correlation between the severity of cerebral degenerative change and clinical diagnosis of patients who died in a psychiatric hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1742982 TI - Integration versus interactive activation: the joint influence of stimulus and context in perception. AB - Empirical results from both reading and speech perception indicate that stimulus and context information have independent influences on perceptual recognition. Massaro (1989) argued that these data are inconsistent with an interactive activation and competition (IAC) model (McClelland & Rumelhart, 1981), and consistent with the fuzzy logical model of perception (FLMP) (Massaro, 1979; 1989). McClelland (1991) than modified the interactive activation model to be stochastic rather than deterministic and to use a best one wins (BOW) decision rule, allowing it to predict independent influences of stimulus and context. When tested against real data, however, the network proposed by McClelland and extended by us gives a poorer description of actual empirical results than the FLMP. To account for the dynamics of information processing, the SIAC model, an interactive model based on the Boltzmann machine, and the FLMP are formulated to make quantitative predictions of performance as a function of processing time. It is shown that the dynamic FLMP provides a better description of the time course of perceptual processing than does interactive activation. The SIAC and Boltzmann models have difficulty predicting 1) context effects given little processing time and 2) a strong stimulus influence given substantial processing time. Finally, we demonstrate that the FLMP predicts that context can improve the accuracy of performance, in addition to providing a bias to respond with the alternative supported by context. In summary, there is now both empirical and theoretical evidence in favor of the FLMP over SIAC models of pattern recognition. We therefore argue that interactive activation is both less consistent with empirical results and not necessary to describe the joint influence of stimulus and context in language perception. PMID- 1742983 TI - Coordinating cognitive information: task effects and individual differences in integrating information from several sources. AB - In many tasks people have to coordinate the information from several sources. An example would be driving a car while listening to directions. The driver has to establish a correspondence between a visual picture and verbal instructions. This paper addresses two questions concerning information coordination. Is there an ability to coordinate information received from several sources that is different from the ability to deal with information from each source, alone? Does coordination simply involve allocating resources to deal with the component tasks, or does the act of coordination itself constitute a separate task? Four experiments examined the coordination of a verbal component task with a visual spatial and with an auditory component task. The results showed that the ability to coordinate perceptual and verbal information is separate from the ability to deal with either perceptual or verbal information, alone. A simple resource sharing model was not adequate in explaining how coordination occurred. We relate our results to a model in which perceptual reasoning occurs independently of verbal processing, but transforming perceptual information into a propositional form is affected by concurrent verbal processing. PMID- 1742984 TI - Recent changes in health related dental behaviors in Norway. AB - There has been a substantial decrease in the prevalence of caries in younger age groups in the western world during the last 15 years. A corresponding increase has been reported regarding use of preventive remedies. Since prevention and control of dental disease is highly dependent upon personal behavior, investigations of dental health behaviors within subgroups of the population are important for future preventive strategies. Occurrence and changes in individual dental health behaviors in Norway were studied through four sets of cross sectional data collected in 1981, 1983, 1985, and 1987. Personal interviews performed by trained interviewers were held with probability samples, each of about 1400 persons, covering the Norwegian population aged 15 and above. During the 6-yr period the proportion of individuals who brushed their teeth and used fluoride dentifrice every day increased. The number of people who used toothpicks or dental floss every day also increased from 1981 to 1985. A marked decrease was, however, observed in use of interdental remedies from 1985 to 1987. Daily use of dental floss was reduced by 10 percent points. Logistic regression showed that the reduction in the probability of using interdental aids was most pronounced among those with few teeth. Lower importance attached to dental health education, at all levels, combined with difficult economic times since 1987, might account for the decrease in daily use of interdental aids in Norway. PMID- 1742985 TI - Knowledge, attitudes and behaviour in relation to dental health of adults in Belfast, Northern Ireland. AB - The aim was to investigate the knowledge, attitudes and behaviour related to dental health of adults living in two neighbouring areas in Belfast, Northern Ireland. 81 adults aged 30 yr or over from two neighbouring residential areas in South Belfast completed a structured interview. The responses of those who retained natural teeth were very different from those who were edentulous. Those in the higher socioeconomic status groups had clearer knowledge, more positive attitudes and more appropriate behaviour related to dental health than those in lower socioeconomic status groups. The differences between the residents of the two areas were less obvious than those noted between the different socioeconomic status groups. It was concluded that the results revealed misconceptions amongst adults in Northern Ireland regarding the causes of dental disease and how it might be prevented both in themselves and in their children. PMID- 1742986 TI - Self-assessment of dental conditions: validity of a questionnaire. AB - In order to determine the validity of dental data obtained from a questionnaire, 100 subjects randomly selected from 2383 respondents were examined clinically. The quality of dental status was ordered in four groups for the number of missing and replaced teeth and for denture status. For the number of missing and replaced teeth, the observed agreement between the clinical diagnosis and the questionnaire answers was 65% for both the maxilla and the mandible, and the agreement estimated by Kappa was 0.52. However, the disagreement was not randomly distributed, since reporting of better dental status than the actual one was much more common than reporting of poorer status. Regarding denture status, the agreement between self-assessment and clinical diagnosis was good; all removable dentures in situ at the clinical examination were reported by the subjects as some kind of denture, although not always the correct type. The results of the study indicate that the use of self-assessment might be reasonable when measuring denture status, and that self-assessment of the number of missing and replaced teeth is a biased estimate of the clinical diagnosis. Thus appropriate action should be taken when using this type of data. PMID- 1742987 TI - Measures of dental disease occurrence. AB - The purpose of the paper is to relate standard epidemiologic and statistical methods for measures of disease occurrence to the description of prevalence proportions and incidence rates of dental diseases. No new concepts are introduced, but the choice of the unit of analysis of numerator and denominator is discussed, and the biological interpretation of the within-patient correlation coefficient is discussed. PMID- 1742988 TI - Correlations between caries prevalence and potential etiologic factors in large samples of 4-5-yr-old children. AB - A data base containing information on dental caries, oral hygiene, gingival state, Streptococcus mutans and lactobacillus counts, and salivary flow rate and buffer capacity in some 2800 4-5-yr-old South African children was created in 1984. The children were equally distributed in four groups; rural black, urban black, urban Indian, and urban white. In this study, the data were used for simple linear correlations between all the factors including caries as well as stepwise multiple regression analyses between caries prevalence and the independent factors in each of the four groups. The highest r value obtained in the single correlations was 0.56 for dmfs/lactobacillus count in the white group. The overall pattern of the groups did not vary much. In the stepwise multiple regression analyses, lactobacilli entered first in all groups. S. mutans and oral hygiene interchanged as Nos. 2 and 3, and gingival state or buffer capacity came out as No. 4. The highest percentage of caries variability explained by these regressions was 25%, in the urban black group, while the lowest was 12%, in the indian group. It was concluded that our generally accepted etiologic factors are unsatisfactory to explain variation in caries in observational studies, which among other things might be ascribed to the inadequate way these factors generally are measured or estimated. PMID- 1742989 TI - Prediction of periodontal bone height from partial radiographic examination. AB - The object of the present study was to determine the relationship between the periodontal bone height as determined from the total dentition and that predicted from a limited number of teeth. The material comprised 247 subjects aged 21-60 yr with an average of 26.3 remaining teeth. All patients were radiographically examined by an intra-oral full mouth survey. The bone height was measured for each tooth and a mean of all single tooth specific values was calculated for each subject. The relationship between the measured value and the predicted value was expressed in terms of correlation coefficients. The correlation between the measured value and the predicted value improved with increasing number of teeth included in the predictor. It ranged from r = 0.79 (single tooth) to r = 0.98 (four teeth). It was concluded that the number of radiographs exposed and teeth examined can be considerably reduced when estimating the alveolar bone height for periodontal screening. PMID- 1742990 TI - Prevalence study of oral precancerous lesions within a complex screening system in Hungary. AB - Previous epidemiological studies, performed in conjunction with compulsory lung screening examinations, showed good results in detecting oral lesions in Hungary, where the mortality rate of oropharyngeal cancer has increased by more than 30% in the past decade. Oral examinations were performed on a district population sample in Budapest, called regularly for X-ray lung examinations. Precancerous lesions and conditions were diagnosed and grouped according to internationally accepted criteria. Oral examinations of 7820 individuals were performed: 42.9% in men and 57.1% in women; 42% of all examined subjects were over 60 yr of age. Oral leukoplakia was diagnosed in 104 cases (1.3%). Histologic examination revealed squamous cell carcinoma in one case. About 70% of oral leukoplakias occurred in men and 30% in women. Oral lichen was diagnosed in six cases (0.08%). The prevalence of smokers was 86.5% in the leukoplakia group as compared with with 29% in the non-lesion group. The new organizational screening model seems to function well in the "risk group" of elderly persons, especially in the early diagnosis of oral cancer and precancerous lesions. PMID- 1742991 TI - Radiographic interpretation and treatment decisions among dental therapists and dentists in Western Australia. AB - All dentists and dental therapists employed in the Community Dental Services in Western Australia were invited to participate in a questionnaire study to find out about their use of radiographs and opinions and knowledge about the diagnosis of approximal caries. Replies were received from 45 dentists (95.1%) and 207 dental therapists (84.0%). Most dentists would not restore a lesion before it appeared on radiograph to have reached the dentine, while therapists were more likely to consider a restoration for a lesion just in enamel. Sixty percent of all respondents thought that a cavity was present when the radiographic lesion was confined to enamel. Fifty-seven percent of dentists thought that an average lesion took at least 12 months to progress from outer enamel to dentine, while a majority of dental therapists thought this would take less than 12 months. Radiographs were not frequently taken by the participants. Operators' opinions about cavity formation were the most important predictor of choice of treatment. In general, these participant's responses were similar to those provided by Norwegian and Dutch respondents in similar surveys conducted 5-6 yr ago, but the present participants worked in an optimally fluoridated area and might therefore have been expected to have adopted more cautious criteria for restorative treatment. Differences between dentists and dental therapists were generally not great. The results suggest that calibration of the operators in the service would offer benefits. PMID- 1742992 TI - Caries experience in the primary dentition of Tanzanian and Finnish 3-7-year-old children. AB - Caries experience of primary teeth in relation to age, sex, ethnic group, socioeconomic status and frequency of consuming sweet snacks and drinks was studied among groups of Tanzanian and Finnish 3-7-yr-olds, a total of 1118 children. In all age groups the Tanzanian children had higher mean dmft scores than Finnish children did. In the Finnish group the mean dmft score was higher at age 7 than at age 3, while in the Tanzanian group no statistically significant difference in dmft scores was found between age groups. In both groups maxillary incisors and molars were the main teeth affected by caries. Frequent consumption of sweet snacks and drinks increased the risk for caries in Tanzanian but not in Finnish children. High socioeconomic status decreased the risk for caries in Finnish children but among Tanzanian children high SES was not associated significantly with the risk of developing caries. According to these results, caries experience in Tanzanian urban nursery school children was significantly higher than in Finnish children of the same age, the differences being especially high among the youngest age groups. PMID- 1742993 TI - Caries prevalence and treatment need amongst children in an Arabian community. AB - A total of 1400 Saudi Arabian children in age groups 6-12 and 15 yr in private and public schools were examined for dental caries and treatment need in the cities of Jeddah (less than 0.30 ppm fluoride in drinking water), Rabagh (0.77 ppm F-) and Mecca (2.47 ppm F-). The mean dmft in 6-yr-olds in private schools in Jeddah was 2.9 compared with 6.3 in public schools (P less than 0.001). The d component accounted for 65% of the total dmft in private schools and 76% in public schools in Jeddah. The mean dmft values in private and public schools in Rabagh were 1.5 and 2.8 respectively and 2.7 and 2.8 in Mecca; the d component accounted for approximately 65% in all groups. The figures for permanent teeth in 12- and 15-yr-olds show similar trends with caries levels being the highest in public schools in Jeddah; approximately 60% of the total DMFT was attributable to the D component in both school types in all three cities. Most of the treatment required in all three cities comprised one- or two-surface fillings. The need for treatment was significantly higher in public schools. PMID- 1742994 TI - Periodontal status of individuals in early stages of human immunodeficiency virus infection. AB - The purpose of this study was to evaluate the association of periodontal health and human immunodeficiency virus infection among individuals in the early stages of disease who were participating in randomized placebo-controlled clinical trials of zidovudine. Previous reports have described a rapidly progressive periodontitis and atypical gigivitis associated with late stages of infection by the human immunodeficiency virus. A health history was completed by each subject. Baseline oral examinations were completed on 97 asymptomatic patients and nine with AIDS-related complex (ARC) during their regular clinic visit. Follow-up examinations were conducted at 3-month intervals throughout the 48 weeks of the oral study. Evaluations of plaque, calculus, gingival abnormalities, caries, and periodontal disease were conducted. Periodontal measurements included plaque index (PI), gingival index (GI), bleeding index (BI), probing depth (PD), and observation for cratering, necrosis, and tooth mobility on six teeth in each patient. More than half of the subjects had visited their dentist during the previous year and had had an oral prophylaxis; less than 25% of them had had either restorative work or extractions. The mean scores for periodontal indices averaged over the course of the study in asymptomatic and ARC respectively were: PI: 0.9 (SE 0.04) and 0.9 (SE 0.08), 0.818; GI: 1.0 (SE 0.04) and 0.9 (SE 0.07), P = 0.412; BI: 0.6 (SE 0.04) and 0.4 (SE 0.07), P = 0.278; PD: 2.9 (SE 0.05) and 2.6 (SE 0.10), P = 0.140. There was no evidence of cratering, necrosis, or tooth mobility in either group. Few had calculus or dental caries. There were no clinically significant differences detected between ARC versus asymptomatic patients. Dental histories and oral examinations showed that two groups of patients in early stages of HIV-disease were in good periodontal health. PMID- 1742995 TI - Dental erosion in a population of Swiss adults. AB - The purpose of this study was to determine the prevalence of dental erosion in an adult population in Switzerland. 391 randomly selected persons from two age groups (26-30 and 46-50 yr) were examined for frequency and severity of erosion on all tooth surfaces. Information was gathered by interview about lifestyle, dietary and oral health habits. For facial surfaces 7.7% of the younger age group and 13.2% of the older age group showed at least one tooth affected with erosion with involvement of dentin (grade 2). 3.5 teeth per person in the younger and 2.8 teeth per person in the older age group were affected. Occlusally, at least one severe erosion was observed in 29.9% of the younger and 42.6% of the older sample with 3.2 and 3.9 erosion-affected teeth per person, respectively. 3.6% of the younger age group and 6.1% of the older age group showed slight lingual erosion on the maxillary anterior teeth. Severe lingual erosions were scarce. Data from interviews and multiple regression analyses revealed that acids from beverages are significantly associated with presence of erosion. PMID- 1742996 TI - Exploration of prediction models for caries risk assessment of the geriatric population. AB - The purpose of this study was to demonstrate a method for establishing a model designed to predict the caries risk of elderly individuals. Twenty-three patients over the age of 65 and living in a semi-independent retirement center were examined; several variables were collected and analyzed for their ability to predict the development of new carious lesions. The analysis was performed using logistic regression where the proportion of new decay was used as the dependent variable. The model for prediction of combined coronal and root caries included the variables flow rate, gender, and root caries index. The proposed method has the advantages of easily collected data, individualized criteria, and the ability to order patients as to the relative risk of developing decay. PMID- 1742997 TI - Relationship between general health, social factors and oral health in women at the age of retirement. AB - Relationships between some medical, psychological, social factors and oral health were analyzed within a comprehensive study of women around the age of retirement. The study was performed in Malmo in 1985-1986 and included 165 women retiring from work between 851201 and 870131. Women in qualified professional positions and with high prosperity indices had an average significantly more remaining teeth and were less often edentulous than the others. The same applied to unmarried women compared to divorcees and widows. There were significant correlations between full blood glucose and serum urate concentrations and number of teeth, DFT and DFS. The mean number of prescribed drugs was negatively related to the number of remaining teeth and high drug consumption was positively related to oral dryness. Women complaining of strain, overwork, restlessness and difficulty in relaxing reported more often problems with oral dryness. Oral dryness was also related to high blood values of calcium, urate and triglycerides, while the serum levels of cholesterol were low. There were no differences between smokers and non-smokers concerning any of the studied tooth related variables, oral dryness, hypertension or bodyweight. The results indicate a close relationship between general health, social factors and oral health. PMID- 1742998 TI - Salivary levels of mutans streptococci, lactobacilli, yeasts, and root caries prevalence in non-institutionalized elderly dental patients. AB - Root caries prevalence was recorded for a consecutive sample of dental patients (n = 146), aged over 55 yr and with at least 12 natural teeth. The mean root DFS score of the males (n = 49) was 6.34 +/- 4.55 and for the females (n = 97) 3.76 +/- 3.31 (P less than 0.001). The salivary levels of mutans streptococci, lactobacilli, and yeasts were determined in addition to salivary flow rate and buffering capacity. Subjects with greater than 1 root DFS had significantly higher salivary levels of mutans streptococci, lactobacilli, and yeasts. They also had fewer teeth and more exposed root surfaces. In step-wise multivariate analyses the factors significantly related to the root DFS score were the number of exposed root surfaces, number of teeth, sex and salivary yeast levels (R2 = 0.41). In the multivariate analyses salivary levels of mutans streptococci were not significantly related to any clinical measurement of root caries experience due to the greater strength of association between the root DFS score and salivary levels of yeasts. Subjects prescribed medicines with a reported xerostomic effect had significantly fewer active root lesions than those not prescribed such medicines and salivary levels of all microorganisms studied were significantly elevated in subjects prescribed medications containing sucrose. PMID- 1742999 TI - Dental health of 5-year-old children in Abu Dhabi, United Arab Emirates. PMID- 1743000 TI - Primary herpetic gingivostomatitis: no longer a disease of childhood? PMID- 1743001 TI - Clinical relevance of a medical history in dental practice: comparison between a questionnaire and a dialogue. PMID- 1743002 TI - TQuery: a context-sensitive temporal query language. AB - Users of electronic medical databases request pertinent information by recasting their clinical questions into a formal database query language. Because the query language is the user's only access to the data, the query language must be powerful enough to enable users to express their data requirements. However, a competing need is for the query language to be restrictive enough so that queries can have unambiguous semantics and the query processor can generate correct answers. We describe a query language, called TQuery , that was designed specifically to formulate database queries that are dependent on temporal and contextual relationships. TQuery specifications express contextual constraints without the need to explicitly reference calendar dates. TQuery is the database query language used to retrieve patient data from an object-oriented electronic patient medical-record system called the temporal network (TNET). TNET and TQuery were developed to support the real-time temporal reasoning and representation needs of a LISP workstation-based medical expert system. PMID- 1743003 TI - A practical method to integrate some stiff systems. AB - A compact, absolutely stable numerical method is presented to integrate stiff systems of pseudo-linear, ordinary, first-order differential equations, commonly found in the simulation of biological models. Solutions are stepwise approximated by a complete set of first order rational polynomials. Mass balance is preserved by the approximations. No matrix inversions are required. Besides being stable, the method is also convergent and can be used with deferred approximation to the limit h = 0. Comparisons between this method and the Stoer-Bullirsch algorithm and fourth-order Runge-Kutta method are presented. PMID- 1743004 TI - A computer program for randomizing patients with near-even distribution of important parameters. AB - In clinical trials, the methods for achieving an event or near-even distribution of important patient parameters have been tedious and often disappointing. In this paper, a computer program for minimizing differences between experimental groups with respect to such important parameters, based on a method described by Traves (Clin. Pharmacol. Ther. London 15, 443, 1974) is presented. The program is available from the author. PMID- 1743005 TI - An empirical analysis of likelihood-weighting simulation on a large, multiply connected medical belief network. AB - We are developing a probabilistic reformulation of the Quick Medical Reference (QMR) system. Our current probabilistic model of the QMR knowledge base of internal medicine consists of a two-level, multiply connected, belief network. Because of the size and connectivity of this belief network, most exact algorithms for calculating the posterior marginal probabilities of diseases are not applicable. In this paper, we analyze the convergence properties of an approximation algorithm, called likelihood-weighting simulation, on the QMR-DT belief network. Specifically, on two difficult diagnostic cases, we examine the effects of Markov blanket scoring, importance sampling, and self-importance sampling, demonstrating that the Markov blanket scoring and self-importance sampling significantly improve the convergence of the simulation on our model. PMID- 1743006 TI - Management of complex immunogenetics information using an enhanced relational model. AB - Flow cytometry has become a technique of paramount importance in the armamentarium of the scientist in such domains as immunogenetics. In the PENGUIN project, we are currently developing the architecture for an expert database system to facilitate the design of flow-cytometry experiments. This paper describes the core of this architecture--a methodology for managing complex biomedical information in an extended relational framework. More specifically, we exploit a semantic data model to enhance relational databases with structuring and manipulation tools that take more domain information into account and provide the user with an appropriate level of abstraction. We present specific applications of the structural model to database schema management, data retrieval and browsing, and integrity maintenance. PMID- 1743007 TI - The role of a clinically based computer department of instruction in a school of medicine. AB - The evolution of activities and educational directions of a department of instruction in medical computer technology in a school of medicine are reviewed. During the 18 years covered, the society at large has undergone marked change in availability and use of computation in every aspect of medical care. It is argued that a department of instruction should be clinical and develop revenue sources based on patient care, perform technical services for the institution with a decentralized structure, and perform both health services and scientific research. Distinction should be drawn between utilization of computing in medical specialties, library function, and instruction in computer science. The last is the proper arena for the academic content of instruction and is best labelled as the philosophical basis of medical knowledge, in particular, its epistemology. Contemporary pressures for teaching introductory computer skills are probably temporary. PMID- 1743008 TI - On the homogeneity of personality disorder clusters. AB - This study was conducted using as subjects persons seeking psychiatric care in a public intake facility. Patients who received a diagnosis of a personality disorder (PD) on axis II constituted the study sample. The study is unique in that it attempts to analyze in a treatment population the relationships between all of the personality disorders (PD) stipulated in DSM-III with emphasis on their relationships to the associated features recorded in the remaining axes of DSM-III. The specific aim of the study was to determine the variation that exists with respect to clinical and demographic variables across the PD clusters categorized in DSM-III and across the PD types of each of the DSM-III PD clusters. In general, considerable inhomogeneity was shown within and across clusters in both demographic and clinical variables, although differences among clusters were noted as well. Cluster B differs prominently from its cohorts with respect to demographic and clinical characteristics. Some of the limitations of these results are emphasized. PMID- 1743009 TI - Alexithymia and depression: distinct or overlapping constructs? AB - Previous research showing moderate to high correlations between the Toronto Alexithymia Scale (TAS) and Beck Depression Inventory (BDI) has generated controversy as to whether alexithymia and depression are distinct or overlapping constructs. The present study addressed this controversy using the statistical method of factor analysis. In a sample of undergraduate university students, a correlation matrix comprising items from both the TAS and BDI yielded a four factor solution with virtually no overlap of the significant factor loadings for the items from each scale, and with the factors corresponding closely with their respective construct. These results were replicated and cross-validated with a sample of psychiatric outpatients. The findings support the view that alexithymia is a construct that is distinct and separate from depression. PMID- 1743010 TI - French views on positive and negative symptoms: a conceptual history. AB - The history of the positive/negative terminology, as applied to psychiatric symptoms, can be divided into an early period of original meanings, a second one of French elaboration, and the current revival. This report addresses issues concerning the meaning, referent, and nature of the link between the positive and the negative as dealt with in French publications by Ribot, Janet, de Clerambault, Nayrac, Von Monakow and Mourgue, and Ey. It is shown how these authors modified the old Reynoldian terminology to meet ongoing epistemological needs, and in doing so exhausted the conceptual permutations through which the positive/negative dichotomy can be put. To render their views intelligible, the historical origin of concepts such as evolutionism, Jacksonian, inhibition, psychological automatism, and synchrony and diachrony is briefly mentioned. It is suggested that the French writers helped to bridge the gap between Reynolds and the present, but that the conceptual subtlety that characterized their work has not been matched by the leaders of the current revival. PMID- 1743011 TI - Philosophy and the DSM-III. AB - This report explores the interface between psychiatry and the DSM-III, arguing that philosophy and psychiatry are of value to one another. Three trends within philosophy are delineated--positivism, hermeneutics, and a synthetic position. These trends are applied to the DSM-III and to specific issues in psychiatric nosology such as the definition of mental disorder, the question of establishing boundaries between different psychiatric disorders, and the differentiation of organic and functional disorders. It is argued that while nosologists often think of themselves along positivist lines, and are often criticized by hermeneutic thinkers for just these assumptions, a synthetic view accounts best for how psychiatric science works. It is concluded that philosophy undergirds psychiatric nosology, while psychiatric nosology raises a series of philosophical questions. PMID- 1743012 TI - Pre-Vietnam contents of posttraumatic stress disorder veterans' service medical and personnel records. AB - We reviewed the pre-Vietnam contents of the service medical and personnel records of 250 Vietnam combat veterans, in an attempt to identify factors predisposing to the development of posttraumatic stress disorder (PTSD). PTSD and non-PTSD veterans did not differ significantly on self-reported medical history items, sick call visits, or military efficiency and conduct ratings. There were trends for PTSD veterans to have lower arithmetic aptitude, more self-reported school difficulties, and (paradoxically) lower pulse rate at military induction. PMID- 1743013 TI - Psychiatric heterogeneity in antisocial alcoholics: relation to familial alcoholism. AB - There is some indication that addicts who qualify for a diagnosis of antisocial personality disorder (ASP) do not comprise a homogeneous group with respect to psychopathology. This preliminary study attempted to determine the extent to which DSM-III diagnosed ASP alcoholics with alcoholism on both sides of their family could be differentiated with respect to childhood behavioral problems and additional adult psychopathology from ASP alcoholics with low degrees of familial alcoholism. Two groups of ASP alcoholic patients were compared: (1) 11 high familial (bilineal) alcoholics, and (2) 22 low familial (nonfamilial or unilineal) alcoholics. Few group differences were found in sociodemographic or alcohol-related characteristics, although the high familial group tended to be younger. However, the high familial alcoholism group tended to report more childhood antisocial behaviors and more childhood behavior problems overall. The high familial alcoholism group also reported more psychopathology on three of the 10 Minnesota Multiphasic Personality Inventory (MMPI) clinical scales, paranoia (P less than .05), schizophrenia (P less than .06), and masculine-feminine (P less than .025). Effect sizes for these three variables were in the moderate range. The group MMPI profile of the high familial alcoholism group was indicative of serious characterological disturbances, while that of the low familial alcoholism group was much more normal. The results of this preliminary study provided evidence suggesting that antisocial individuals with a high degree of familial alcoholism are more likely to manifest psychopathology than antisocial individuals with a lesser degree of familial alcoholism. PMID- 1743014 TI - An empirical examination of soothing tactics in borderline personality disorder. AB - Little empirical information is available regarding the process of self-soothing in borderline individuals, as well as in normal subjects. This study examined the frequency of used of soothing "things," soothing "behaviors," and soothing "psychological activities" in three groups: borderline personality disorder, major depressive disorder without concurrent personality disorder, and college students. Results indicated that: (1) borderline individuals reported using soothing things at comparable levels to the other two groups; (2) borderline subjects and those with major depressive disorders used more adaptive soothing behaviors than did college students; (3) borderline subjects used more maladaptive soothing behaviors than the other two groups; and (4) borderline individuals used psychologically soothing activities at frequencies comparable to the other two groups. These results are intended to begin the process of developing a soothing profile for individuals with borderline personality disorder. PMID- 1743015 TI - Social breakdown in the elderly, I. Case studies and management. AB - This report focuses on the syndrome of social breakdown of the elderly (SBE), which, although common, has attracted surprisingly little attention in clinical geropsychiatry. Profound social isolation, extreme neglect of self-care, and stubborn refusal of help are the main characteristics of SBE. In most cases, the syndrome of SBE is part of a well-defined major psychiatric illness (secondary SBE). In other cases, stressful life events cause lifelong personality abnormalities to deteriorate into full-blown syndrome of SBE (pure SBE). Two detailed case histories highlight the clinical features of pure SBE and its management. PMID- 1743016 TI - Social breakdown in the elderly, II. Sociodemographic data and psychopathology. AB - Current understanding of the sociodemographic and psychopathological characteristics of the syndrome of social breakdown of the elderly (SBE) is reviewed. In DSM-III-R terms, pure SBE may be best classified as an adjustment disorder with profound social withdrawal. It is argued that pure SBE is a form of "personality development" in accord with Jaspers's concept of meaningful connections. PMID- 1743017 TI - DSM-III-R personality disorders in panic and obsessive-compulsive disorder: a comparison study. AB - Forty-eight patients with panic disorder/agoraphobia (PAD) and 30 with obsessive compulsive disorder (OCD) were assessed for DSM-III-R axis II personality disorders (PD) and the presence of the same anxiety disorder in the relatives of probands (homotypic disorders). No specific personality disorder was present significantly more often in either of the two groups. Agoraphobia was not associated with higher rates of axis II disorders in PAD patients. Duration of illness did not influence the presence of a PD in patients of both groups. Secondary cases of the same anxiety disorder were significantly more common among first-degree relatives of PAD patients. A discriminant analysis performed on the most frequent personality traits of both groups provided a correct classification of cases of 97.4%. Our results do not support the hypothesis of PD as secondary to anxiety disorders and confirm previous findings of a lack of specificity between DSM-III-R axis II categories and OCD and PAD. PMID- 1743018 TI - Causal attributions in first-degree relatives of depressed and agoraphobic inpatients. AB - Causal attributions in 77 first-degree relatives of major depressed, agoraphobic, major depressed and agoraphobic (comorbid), and dysthymic inpatients were studied. The hypothesis that the relatives of comorbid and dysthymic patients should exhibit more "depressogenic" causal attributions for bad events than the relatives of major depressed and agoraphobic patients was partly supported. Relatives of dysthymic patients attributed bad events to more internal causes and assigned more importance to the events themselves than did relatives of major depressed patients. Relatives of patients with major depression and agoraphobia comorbidity attributed bad events to more internal causes than did the relatives of major depressed patients. Statistically controlling for differences in sex, age, social class, and depressive symptom level did not significantly alter the results among the four groups. PMID- 1743019 TI - An attempt to evaluate the risk factors related to coronary heart disease in Hungary. AB - Using questionnaires, the authors evaluated the risk of coronary heart disease in different groups of Hungarian society. Among physicians, teachers, factory workers and agricultural workers, the latter seem to be at the highest risk. On the basis of these results obtained in a population of 363 agricultural employees, a detailed risk factor analysis was made. These results were compared with those of the Framingham Offspring Study. Hungarians show alarmingly often a high blood cholesterol level, hypertension, smoking and obesity (the latter factor in women). The more frequent occurrence of the three main risk factors (high blood cholesterol, hypertension, smoking) in young Hungarians is concordant with the fact that the incidence of myocardial infarction in young people in Hungary is one of the highest in the world. The frequency of a positive parental history and obesity in men is lower in the Hungarian population than in the American one. The risk of coronary heart disease in the examined Hungarian population is considered high. The authors have launched a preventive programme. PMID- 1743020 TI - Diagnosis of myocardial ischaemia by means of precordial ST mapping and exercise 201-thallium scintigraphy. AB - The authors compared the results of examination by means of exercise precordial ST mapping and exercise 201-thallium scintigraphy in 43 patients with ischaemic heart disease and in 10 controls. The methods have been found to be equally helpful in establishing the diagnosis of myocardial ischaemia. 201-thallium scintigraphy is preferred when trying to quantify the lesion and to localize it. The currently available techniques of exercise EGG mapping do not always make determination of ischaemia distribution possible. The benefits inherent in either method are their non-invasiveness and good reproducibility, features making them ideal tools for assessing the effect of treatment. PMID- 1743021 TI - Determination of elastin-antielastin circulating immune complexes in serum of normal subjects and atherosclerotic patients. AB - Healthy subjects of different ages and a group of atherosclerotic patients were tested for the presence of elastin-antielastin circulating immune complexes (CIC) in their sera. For the purpose the authors used a method based on sequential precipitation with rising concentrations of polyethylene glycol (PEG), dissociation of the precipitated CIC and further analysis of the resuspended precipitates for the presence of elastin derived peptides by an enzyme-linked immunosorbent assay (ELISA). Elastin-antielastin CIC were detected only in the serum of atherosclerotic patients and that of healthy subjects over 60. The elastin-antielastin CIC obtained from the serum of atherosclerotic patients were precipitated by higher PEG concentrations mainly and had a higher elastin content in comparison with those isolated from the serum of healthy persons over 60. PMID- 1743022 TI - Angiographic evidence of coronary artery ectasia: our experience. AB - The purpose of this angiographic study was to make a review of patients with coronary artery ectasia (CAE) and to compare the average coronary artery diameters of proximal, middle and distal segments of the following three groups of coronary arteries: Group E (ectatic segments in patients with CAE and ischaemic heart disease), Group E-n (presumably normal segments in the same group of patients) and Group N (normal coronary arteries of control patients). It was found that distal segments of all three coronary arteries and the middle segment of the circumflex artery in Group E-n were significantly narrower than the corresponding segments in Group N (p = 0.001 or less than 0.05 respectively), which suggested the arteriosclerotic origin of both, CAE and distal coronary artery involvement. PMID- 1743023 TI - Essential hypertension and insulin resistance. AB - Insulin resistance (IR) appears to be an important risk factor of both hypertension and atherosclerosis. Moreover, it is present also in obesity, dyslipoproteinaemia and non-insulin dependent diabetes. IR could be found in untreated hypertension and even in normotensive children of hypertensive parents. It alters carbohydrate, lipid and protein metabolism and participates directly in the development of hypertension. The diagnosis of IR is possible by simple determination of insulin and glyceamia during glucose tolerance test. The differential diagnosis is obligatory because IR is not specific just for hypertension. Treatment, with the exception of nonpharmacological measures, is unsatisfactory. However, results of newest research are highly promising. PMID- 1743024 TI - What are the causes of unsatisfactory control of arterial hypertension in the population? AB - A cross-sectional epidemiological study was conducted in the late 1980's in 660 men and 440 women, aged 35-60 years to assess the level of control of arterial hypertension (AH) in an industrial population. A relatively high rate of blood pressure (BP) assessment was found; only 2% of those screened had never their BP measured. Despite this, 44% of men and 40% of women with a high BP were unaware of their AH and conversely 15% of women and 12% of men with a positive history of AH were found to have BP less than 140/90 mmHg. Sufficient AH control was provided only in one fifth of the total amount of 300 hypertensive subjects. The paper evaluates the detection rate of our epidemiological study designed to assess the current status of control of AH and the causes of the unsatisfactory level of detection and control of a high BP are discussed. PMID- 1743025 TI - The effect of acute and chronic nitrate administration in precapillary and postcapillary pulmonary hypertension. AB - The effect of nitrates was monitored in 16 patients with precapillary, and in 12 patients with postcapillary pulmonary hypertension (PH). The patients had haemodynamic examination on acute administration of 10 mg of isosorbide nitrate (ID) in infusion and after 2-month therapy with 120 mg of isosorbide dinitrate retard daily. Acute ID administration decreased filling pressure of both ventricles, pulmonary and aortic pressure, pulmonary and systemic resistance and increased blood flow. No significant difference was found between the two types of PH. Long-term administration resulted in a statistically significant decrease in filling pressure (in both ventricles) and pulmonary pressure, even though the decrease was less pronounced than those seen following acute administration. Again, no statistical differences were noted between the two types of PH. While acute administration of nitrates decreases both preload and afterload, chronic administration decreases only preload. The implications of this finding for therapeutic practice are discussed. PMID- 1743026 TI - Acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: is there a relationship? PMID- 1743027 TI - Computer analysis of drug therapy in cardiac patients. Preliminary communication. AB - The authors present a system of computer control in drug therapy of cardiac patients aimed at preventing complications and adverse interactions of simultaneously administered drugs. The system includes data on the 196 most frequently used cardiac drugs and 433 other drugs showing clinically important interactions with cardiac drugs. PMID- 1743028 TI - Cathepsin D activity of an aortic polyester double velour DALLON graft. AB - Cathepsin D activity, protein and acid-soluble tyrosine contents in a polyester double velour DALLON graft were evaluated in an experiment lasting one year, performed in 36 male mongrel dogs. The cathepsin D activity in the intimal, medial and adventitial layers of the graft on the 7th day of the experiment was much higher than in a normal artery and vein. In the intimal and medial layers of the graft, this activity increased in the 1st and 4th months of the experiment. In all the layers, cathepsin D activity fell to the level of the activity in normal vessels after one year of the experiment. The protein and acid-soluble tyrosine contents in all the graft layers were highest on the 7th day after which they decreased gradually. PMID- 1743029 TI - Dynamics of lipid peroxidation in isoprenaline-induced myocardiopathy. AB - The dynamics of lipid peroxidation in isoprenaline-induced myocardiopathy was studied in rats. Spontaneous and Fe(II)- catalyzed generation of malondialdehyde (MDA)-like products and chemiluminescence in the heart, liver and brain homogenates were measured. The increase in the interval between treatment of rats with isoprenaline and their killing up to 48 hours led to an increase in MDA content in the heart. Both spontaneous and Fe(II)-induced chemiluminescence also reached their maxima after 48 hours. These data show that well expressed lipid peroxidation in the rat heart occurs approximately 48 hours after isoprenaline application. Isoprenaline metabolization in the liver leads to generation of activated oxygen species which are able to induce lipid peroxidation in the presence of Fe(II). The treatment of rats with isoprenaline caused well-expressed lipid peroxidation in the brain. The maximum of this process occurred approximately 36 hours after isoprenaline application. The results show that both spontaneous and Fe(II)-induced chemiluminescence might be used for the estimation of lipid peroxidation in rat heart homogenates. PMID- 1743030 TI - The functional state of the creatine kinase system of myocardial mitochondria in alcoholic cardiomyopathy. AB - The authors studied the chronic effect of ethanol on the functional state of creatine kinase system in myocardial mitochondria of adult rats. Mitochondrial functions were determined in skinned fibres prepared according to Veksler without mitochondria isolation. Compared with control values, ethanol was found to decrease statistically significantly the velocity of creatine-stimulated mitochondrial respiration (Vcr) and that of maximum ADP-induced stimulation of mitochondrial respiration (Vmax). The chronic action of alcohol also reduces the respiratory activation by creatine (%Cr) which ranks among the most sensitive indicators of mitochondrial respiration regulation by creatine kinase. The authors have demonstrated that the function of the creatine kinase system of myocardial mitochondria is impaired in alcoholic cardiomyopathy in the adult rat. PMID- 1743031 TI - Differential asymmetries for positive and negative emotion: hemisphere or stimulus effects? AB - Two experiments were carried out to determine whether expressive asymmetries in facial stimuli might underlie evidence of differential hemispheric responses to positive and negative emotion. Experiment 1 systematically varied stimulus orientation; Experiment 2 included both normally oriented and reversed (mirror image) faces. We replicated previous reports of a left field advantage for happy faces and a right field superiority for sad faces only when normally oriented faces were used. Mirror-image stimuli tended to produce the opposite pattern of results, and a combination of the two (Exp. 2) eliminated the visual field differences for each emotion. The findings underscore the importance of controlling for stimulus asymmetries in visual laterality studies, and are discussed in terms of current notions about the lateralization of both the perception and expression of emotion. PMID- 1743032 TI - A longitudinal study of word-reading ability in Alzheimer's disease: evidence from the National Adult Reading Test. AB - The purpose of this longitudinal study was to examine word-reading ability of subjects with probable Alzheimer's disease (AD), using the National Adult Reading Test (NART). In addition to the NART, a battery of neuropsychological tests was administered to 18 AD and 20 elderly control subjects at yearly intervals over 3 years. Repeated measures analysis with grouping factors showed that the controls scored better than AD subjects on the NART at each test date and the AD subjects scored significantly worse over time. NART scores were significantly correlated with dementia severity in AD subjects at final testing only, suggesting that the NART is sensitive to dementia severity only at the later stages of the disease. Associations between the NART and other cognitive measures yielded few significant results. Finally, error responses to NART words were summarized by type and percentage for each group at each test session. PMID- 1743033 TI - A new test of object decision: 2D silhouettes featuring a minimal view. AB - A new test of object decision in which a minimal view 2D silhouette of an object is presented together with 3 nonsense shapes has been administered to a consecutive series of patients with right and left hemisphere lesions. There was a significant deficit in the right hemisphere lesion group as compared with the left hemisphere group. It is concluded that this object decision test provides a measure of the integrity of pre-semantic perceptual processing systems. PMID- 1743034 TI - The relationship of depression to symptomatology and lesion site in aphasic patients. AB - The prevalence of depression was examined in 54 patients recruited by speech pathologists and separated into four groups according to aphasia type (Broca's vs Wernicke's) and the duration of illness (less than six months vs more than six months). Evaluation of depression was made through questionnaires, completed by the spouse or speech pathologist, and patient interviews. The four groups were similar in demographical variables, in severity of aphasia and in lesion size (from CAT scan analyses). The prevalence of depression for the total sample was low (15%). Univariate analyses (ANOVA) did not show significant differences between the groups on the depression scales. The severity of depression was not correlated with lesion size or location. It was concluded that Wernicke's aphasics do not experience depression less often nor less severely than Broca's aphasics and that the incidence of depression in aphasia is not high. These results are in contrast with those obtained in earlier studies. Reasons for the discrepancies between this and other studies are discussed. PMID- 1743035 TI - Increased reading speed for words and pronounceable non-words: evidence of preserved priming in amnesics. AB - Twelve amnesics with various aetiologies were compares with 12 matched control subjects on a task which examined the increase in reading speed for lists of words and pronounceable non-words that were shown several times and read twice during a training phase. After a four minute delay the reading speed for the primed lists was compared with that for an equal number of umprimed lists. No non specific practice effects were observed. The amnesics showed an equal proportional increase in reading speed for primed words list to that of their controls, and, if anything, a slightly greater reading speed increase for non words. These effects were found even when an amnesic subgroup, selected because its baseline reading speed was closely matched to that of the controls, was used for the comparison. The patients' preserved priming for the novel information found in the non-word list reading task occurred in conjunction with very impaired free recall for the contents of the lists. The effects occurred in patients of all aetiologies used in the study and confirm and extend the findings of Moscovitch, Winocur and McLachlan (1986). PMID- 1743036 TI - Confabulation following aneurysm of the anterior communicating artery. AB - Nine subjects with aneurysms of the anterior communicating artery (ACoA) and 17 subjects with other intracranial hemorrhages (ICH) were evaluated for confabulatory responses under two naturally occurring conditions: (1) when subjects were not oriented to person, place, month and year, (2) when subjects were fully oriented. Confabulation was observed in all 9 of ACoA patients both during disoriented and oriented periods. In contrast, 7/17 of the other ICH patients showed signs of confabulation while disoriented, whereas only one continued to display confabulatory tendencies while fully oriented. Confabulation was more severe in the ACoA group. These data suggest that the confabulation observed in the other ICH group may be secondary to an acute confusional state while the prolonged confabulation in ACoA patients may be a manifestation of a more primary cerebral disorder. PMID- 1743037 TI - Interhemisphere transfer in males and females. AB - Sex differences in the speed of interhemisphere transfer of visual information were assessed by means of a modified version of a task on which Potter and Graves (1988) have recently reported significantly lower error rates in females. The main aim was to examine the effect of including a control condition in which stimuli are presented centrally. In the light of their results, it was predicted that any advantage to females would be restricted to the peripheral condition since central presentations do not necessarily require interhemisphere transfer. Response latencies and errors were measured. No interaction between sex and position of presentation was found to occur. It is suggested that the lower error rates observed by Potter and Graves in females may have been the result of sex differences in speed-error trade off rather than in interhemisphere transfer. PMID- 1743038 TI - Korsakoff amnesics are poor at judging the sequence of two tones. AB - Alcoholic amnesics were given a test of temporal sequencing ability devised by Efron which has practically no memory component. These amnesics were very impaired on the task. However, the extent of this impairment did not relate to the magnitude of their "target memory" deficit nor did it relate to the ability to make temporal judgements from memory. Two other groups of amnesics (3 post encephalitis and 4 with ruptured aneurysms of the anterior communicating artery) did not show impairments on the sequencing task. Data from the amnesic patient N.A. (who was unimpaired on the task), three other amnesics (who showed a tendency to be poor at the task) and two frontally damaged patients (one of whom performed especially badly on the sequencing task but had no obvious memory difficulties) were also presented. It is argued that deficits in temporal discrimination may not be found in all amnesics but, when they are observed, are an incidental feature related to additional (possibly cortical damage. Implications of the results for the view that amnesia results from a deficit in the use of contextual information (including temporal information) are considered. PMID- 1743039 TI - Anterior corpus callosum atrophy and verbal fluency in multiple sclerosis. AB - To determine whether different portions of the corpus callosum (CC) are responsible for transferring the information of specific cognitive modalities, eighteen females with relapsing-remitting Multiple Sclerosis (MS) were studied using neuropsychological procedures and Magnetic Resonance Imaging (MRI). Measures of both anterior and posterior CC areas were obtained in patients with MS as well as in eighteen age and sex matched healthy controls. MRI scans were additionally analyzed for each patient in order to evaluate the extent of demyelinating lesions in both periventricular and subcortical areas. Patients with MS exhibited a significant decrease in both the anterior and posterior CC areas compared with normal subjects. The results of statistical analysis showed that, even when the effect of demyelinating lesions was taken into account within a regression equation, the atrophy of anterior CC area strongly affected the performance on verbal fluency task. These data emphasize the importance of the anterior CC area for the interhemispheric transfer of cognitive information associated with verbal fluency. PMID- 1743040 TI - Number impairments following hypokalemia: a case study. AB - A case study is reported of a 55 year old female (B.B.) who complained of significant difficulty manipulating and remembering numbers. Twenty-four years prior to the present complaint, B.B. had been hospitalized for idiopathic hypokalemia and secondary hyperaldosteronism. The present study examined the nature and extent of B.B.'s cognitive impairments. On standardized and experimental tests of intelligence and general cognitive ability, she scored quite well. However, she demonstrated significant impairments in digit span, number processing and calculation, memory for biographical details involving numbers and general number knowledge. The implications of such a constellation of impairments are discussed from both cognitive and neurological perspectives. PMID- 1743041 TI - Instruction effects on gender differences in visual field advantages during lexical decision tasks. AB - Two experiments explored the effects of speed, accuracy, on speed and accuracy instructions on visual field advantages to lexical decisions in males and females. In Experiment 1, right visual field advantages in reaction time appeared in the groups of males in the accuracy condition and in the speed and accuracy condition. In Experiment 2, feedback consistent with the instructions was given to subjects. Females and males in the accuracy condition showed a right visual field advantage in the second block of trials. These findings suggest that cognitive variables mediate right visual field advantages to lexical decisions in males and females. PMID- 1743042 TI - Pure apraxic agraphia with recovery after drainage of a left frontal cyst. AB - A case is reported of isolated apraxia of writing in which general limb praxis was spared. Spontaneous writing, writing to dictation and copying were equally affected. Letter selection and spelling were preserved and other language functions intact. A CT scan revealed a left frontal arachnoid cyst. After surgical drainage the agraphia resolved. The anatomical basis of the disorder is discussed in the light of modern information processing models of writing. PMID- 1743043 TI - Hemispheric differences in the processing of pictures of typical and atypical semantic category members. AB - In the following experiment, pictures of typical and atypical category members were categorised by subjects after presentation to either the left or right visual field. Three different categories were investigated. The results in part replicate a previous study by Zaidel (1987), who found an interaction between visual field and typicality. She suggested this result might reflect different conceptual organisations for each hemisphere. However, in the present study, the Visual Field x Typicality interaction was not evident in the two other categories investigated, and it is argued that any conclusion regarding conceptual organisation may be premature. Further work is needed to address the issue. PMID- 1743044 TI - Therapy of upper gastrointestinal tract cancers. AB - Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases. PMID- 1743045 TI - Recent articles of nutritional interest to pediatricians. PMID- 1743046 TI - Foster children and the foster care system, Part I: History and legal structure. PMID- 1743047 TI - Immunizations. PMID- 1743048 TI - Kawasaki syndrome. PMID- 1743049 TI - Pleural diseases: multimodality imaging and clinical management. AB - The parietal and visceral pleura are specialized membranes which are highly efficient in keeping the pleural space essentially dry and free of protein and particulate matter. Radiology has played a pivotal role in the understanding of pleural diseases because radiography and, more recently, computed tomography (CT), sonography, and magnetic resonance imaging (MRI) have allowed in vivo visualization of abnormalities. In addition, these newer modalities have been invaluable in guiding diagnostic and therapeutic measures. Cross-sectional imaging techniques, particularly CT, are frequently of assistance in determining whether tube thoracostomy or other surgical measures are indicated, and when these procedures should be performed. The application of newer imaging modalities in expediting the management of pleural diseases is emphasized. The anatomy, histology, and physiology of the pleura, in both normal and disease states, are also reviewed. PMID- 1743050 TI - Cardiothoracic trauma. PMID- 1743051 TI - The use of antibiotics in general surgery. PMID- 1743052 TI - How do sperm activate eggs? PMID- 1743053 TI - Proteoglycans in development. PMID- 1743054 TI - Development of mouse hematopoietic lineages. PMID- 1743055 TI - Dorsal-ventral pattern formation in the Drosophila embryo: the role of zygotically active genes. PMID- 1743056 TI - Control of cell lineage and cell fate during nematode development. PMID- 1743057 TI - Inducing factors and the mechanism of body pattern formation in vertebrate embryos. PMID- 1743059 TI - A new adventure. PMID- 1743058 TI - Patterning of body segments of the zebrafish embryo. PMID- 1743060 TI - A dermatologic dairy. Portrait of a practice. PMID- 1743061 TI - Space dermatology: a specialty in evolution. AB - The last thirty years have demonstrated the ability of humans to survive both brief and prolonged durations of microgravity in the unique environment of space. The maintenance of health and well-being during spaceflight has been the focus of physicians and health care personnel involved in space medicine. It follows that dermatology will become a defined component of space medicine, as skin-related physiology and subsequent disorders are elucidated and as health maintenance protocols are developed. This information will become part of the core of what can be called space dermatology. PMID- 1743062 TI - Human experience in space. AB - Dr. Carr recounts his own experience in space on the Skylab III mission. He notes that medical research in space continues today, and compares current Shuttle missions with those of Skylab. PMID- 1743063 TI - Physiological changes during spaceflight. AB - Before human beings first explored space, many dire predictions from the scientific community suggested that weightlessness was not compatible with life. Although these prophesies have been proven false, many physiological alterations do occur in microgravity conditions. Other systems are altered as well, but the cardiovascular, musculoskeletal, and immune systems undergo adaptations that may pose problems for the space traveler, especially on returning to gravity. PMID- 1743064 TI - Space nursing. AB - Rogers' nursing science of unitary human beings has potential for providing a unique understanding of human life and health in space as well as on Earth. When planning for nursing services beyond the planetary level, we must focus these on people as integrated wholes in mutual process with a radically different environment. The overview effect, as experienced by astronauts and others, suggests that future space inhabitants are precursors of spacekind. PMID- 1743065 TI - Cutaneous wound healing in space. AB - With the expected increase in extended-length space exploration missions and the establishment of permanent space stations, there is an increased chance of cutaneous injury occurring in astronauts due to trauma or unexpected emergency surgery. Will these wounds heal properly in space? This question remains unanswered. Several basic areas of the wound healing process need to be investigated through controlled scientific studies on spaceflights. PMID- 1743066 TI - A brief history of trying: man, NASA, and medicine. AB - The development of the V2 rocket during World War II raised the possibility of manned spaceflight to the level of "serious consideration." Concepts of aviation medicine led to the specialty of space medicine. Projects Mercury, Gemini, Apollo, Skylab, and Apollo-Soyuz, and the Space Transportation System have helped us gain important biomedical information, including but not limited to, microgravity and its effects on red cell mass, orthostatic tolerance, exercise capacity, bone density, and muscle nitrogen levels. Problems of "space motion sickness" and micro-organisms in space have become major concerns. This analytic review covers these topics and relevant others. PMID- 1743067 TI - A health maintenance facility for space station freedom. AB - We describe a health care facility to be built and used on an orbiting space station in low Earth orbit. This facility, called the health maintenance facility, is based on and modeled after isolated terrestrial medical facilities. It will provide a phased approach to health care for the crews of Space Station Freedom. This paper presents the capabilities of the health maintenance facility. As Freedom is constructed over the next decade there will be an increase in activities, both construction and scientific. The health maintenance facility will evolve with this process until it is a mature, complete, stand-alone health care facility that establishes a foundation to support interplanetary travel. As our experience in space continues to grow so will the commitment to providing health care. PMID- 1743068 TI - The history of the Space Dermatology Foundation. AB - The five-year history of the Space Dermatology Foundation is reviewed. How the organization was conceived, its purpose, and what it intends to accomplish are presented. PMID- 1743069 TI - History of self-experimentation in dermatology: should we go first--sometimes? AB - Because of its availability, the skin has been used over the years for self experimentation. Many examples can be cited, including the heroic self experiments of Carrion of Peru with verruga peruana and those of Goldberger with pellagra and Pediculoides ventricosus. My personal self-experimentation began with sensitization to Japanese lacquer. From that starting point I experimented with chemical warfare agents, cortisone versus hydrocortisone, bites of various arthropods, and finally, experiments with lasers. Some dermatologists will continue to do self-experimentation when they acquire infections from their patients. I believe that sometimes, for their patients' benefit, they should go first. PMID- 1743070 TI - Transcribed and nontranscribed parts of the human ribosomal gene repeat show a similar pattern of distribution in nucleoli. AB - The distribution pattern of the transcribed and nontranscribed parts of human ribosomal RNA genes were visualized simultaneously in the same cells by nonautoradiographic in situ hybridization. DNA probes labeled with either digoxigenin or biotin were detected in the same cells by different fluorescence systems. The signals from both the transcribed and nontranscribed parts showed a similar distribution pattern. This finding is not compatible with the conclusion, suggested by earlier studies, that the transcribed and nontranscribed parts of the rRNA genes are located at different sites within the nucleoli or in different nucleolar components. PMID- 1743071 TI - A low-copy repeat located in subtelomeric regions of 14 different human chromosomal termini. AB - Two cosmid clones, cG1A3 and cG1A6, containing large blocks of a telomeric repeat sequence, (TTAGGG)n, were isolated independently. Restriction mapping and fingerprinting studies suggested that cosmid cG1A6 is entirely contained within cG1A3. Competitive in situ hybridization localized cG1A3 to 14 different human telomeres and one internal site at 2q14----q21, indicating the presence of a subtelomeric low-copy repeat within this cosmid. PMID- 1743072 TI - Localization of the gene encoding insulin-degrading enzyme to human chromosome 10, bands q23----q25. AB - Insulin-degrading enzyme (IDE) is a cytosolic proteinase involved in the cellular processing of insulin. Using somatic cell hybrid analysis and in situ chromosomal hybridization, we have localized the gene encoding IDE to human chromosome 10, bands q23----q25. The murine Ide gene was previously mapped to Chromosome 19; together, these results suggest that the IDE gene is a member of a conserved syntenic group on human chromosome 10, bands q23----q25 and mouse Chromosome 19. PMID- 1743073 TI - Ribosomal RNA gene site polymorphism in Bufo terrestris. AB - Individual specimens of Bufo terrestris were discovered that possessed ribosomal gene locations in addition to those normally found. Every specimen from an island population that was examined had extra sites, whereas fewer individuals from coastal mainland populations and none from inland populations had them. Although the extra ribosomal gene locations probably did not arise through gross structural chromosome rearrangements, their origin remains unclear. PMID- 1743074 TI - Failure of chromosomally abnormal sperm to participate in fertilization in the Chinese hamster. AB - The selection of chromosomally abnormal gametes was investigated in the Chinese hamster by direct chromosome analysis of meiotic cells and one-cell embryos obtained from crossing heterozygotes for two reciprocal translocations, T(1;3)7Idr and T(1;3)8Idr. Expected frequencies of male and female gametes with different chromosome constitutions were estimated by scoring of secondary meiotic metaphase (MII) cells in the translocation heterozygotes. The frequency of gametes with each karyotype that participated in fertilization was investigated in pronuclei from translocation heterozygotes in one-cell embryos obtained from crossing the heterozygotes with karyo-typically normal animals. Compared with the expected frequencies from MII scoring, the frequencies of male pronuclei having some karyotypes in one-cell embryos decreased significantly. The karyotypes of male pronuclei showing a decreased frequency were commonly characterized by a deficiency of the long-arm segment of chromosome 1 (q13----qter) or by a deficiency of almost the whole arms of chromosome 3. On the other hand, the frequencies of female pronuclei with the same karyotypes were all consistent with those estimated from MII scoring. These results suggest that sperm nullisomic for certain segments of some chromosomes may fail to participate in fertilization. PMID- 1743075 TI - Chromosomal localization of the major histocompatibility complex (MHC) in the rhesus monkey and chimpanzee by fluorescence in situ hybridization. AB - Genes for the major histocompatibility complex (MHC) were localized by fluorescence in situ hybridization to the long arm of rhesus monkey chromosome 5. This localization contradicts previous reports, based on genetic investigation of somatic cell hybrids, that placed the MHC on chromosome 2 of this species. In the chimpanzee, the MHC loci were localized to 5p21.3, corresponding precisely to their location on human chromosome 6p21.3. PMID- 1743076 TI - Cytological evidence of maternal meiotic errors in a line of chickens with a high incidence of triploidy. AB - Direct evidence of the nature of maternal meiotic errors in a selected line of chickens with a high incidence of triploidy was obtained by using cytologically marked paternal gametes derived from a closely related avian species. Matings were made by artificial insemination of female chickens of the selection line and a control line with semen from ring-necked male pheasants. A total of five triploid, one pentaploid, and 21 diploid hybrid embryos were karyotyped. Each triploid hybrid embryo contained one set of paternal pheasant chromosomes and two sets of maternal chicken chromosomes, providing irrefutable cytological evidence that the triploids were derived from diploid ova produced by females of the selection line. The pentaploid hybrid contained one set of paternal pheasant chromosomes and four sets of maternal chicken chromosomes, indicating that it had been derived from a tetraploid ovum. Females of the selection line are thought to have a genetically mediated susceptibility to nondisjunction which is responsible for the high incidence of meiotic errors. Evidence is provided that the non disjunction occurs at both meiosis I and meiosis II. PMID- 1743077 TI - [Two additional cases of autosomal trisomy, 61,XY,+12 and 61,XX,+12, in cattle]. AB - Two new cases of trisomy of chromosome No. 12 in cattle are reported. The phenotypic effects of this chromosome aberration are described and discussed. PMID- 1743078 TI - C-band polymorphisms in exotic inbred strains of mice: a method for mapping centromeric ends of chromosomes. AB - The major satellite DNA of Mus musculus appears as a pericentromeric heterochromatin block in all chromosomes but the Y. While C-banding readily reveals the presence of this heterochromatin block, there is considerable polymorphism in C-band size among the chromosomes and among different subspecies. We have studied the distribution of C-band size differences in the chromosomes of 15 exotic inbred laboratory strains and substrains derived from wild populations of different subspecies of M. musculus. The variation in C-band size among these inbred strains can serve as a useful codominant cytological marker for estimating recombinational distances between the centromere and proximal genes in linkage crosses. PMID- 1743079 TI - The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region. AB - Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm. PMID- 1743080 TI - Synapsis and obligate recombination between the sex chromosomes of male laboratory mice carrying the Y* rearrangement. AB - The synaptic and recombinational behavior of the sex chromosomes in male laboratory mice carrying the Y* rearrangement was analyzed by light and electron microscopy. Examination of zygotene and pachytene X-Y* configurations revealed a surprising paucity of the staggered pairing configuration predicted from the distal position of the X pseudoautosomal region and the subcentromeric position of the Y* pseudoautosomal region. When paired at pachynema, the X and Y* chromosomes usually assumed configurations similar to those of typical sex bivalents from normal male laboratory mice. The X and Y* chromosomes were present as univalents in more than half of the early- and mid-pachytene nuclei, presumably as a result of steric difficulties associated with homologous alignment of the pseudoautosomal regions. When paired at diakinesis and metaphase I, the X and Y* chromosomes exhibited an asymmetrical chiasmatic association indicative of recombination within the staggered synaptic configuration. Both pairing disruption and recombinational failure apparently contribute to diakinesis/metaphase I sex-chromosome univalency, as most cells at these stages possessed X and Y* univalents lacking evidence of prior recombination. Recombinant X or Y* chromosomes were detected in all metaphase II complements examined, thus substantiating the hypothesis that X-Y recombination is a prerequisite for the normal progression of male meiosis. PMID- 1743081 TI - For the love of Tony and Joanne, Tenci, Kristi, Wayne, Robie and Ricky. PMID- 1743082 TI - [Illustration of vertical control in hyperdivergence with the Tweed technique]. PMID- 1743083 TI - [Why become a dentist?]. PMID- 1743084 TI - [The cauterizing cement of J. J. Borgne, Brussels dentist in 1869]. PMID- 1743085 TI - [Interconnection between sensitivity to ouabain and malignancy in murine cells]. PMID- 1743087 TI - [Basic characteristics of a parallel dual DNA helix by scanning tunnel microscopy data]. PMID- 1743086 TI - [Structural-functional state of artificial and native membranes under the effect of antineoplastic agents based on platinum coordination complexes]. PMID- 1743088 TI - [Enzymatic-transport system of epithelial cells, stroma, and the muscle-serous layer of the rat small intestine]. PMID- 1743089 TI - [A new secreted protein from Saccharomyces cerevisiae, stimulated by heat shock]. PMID- 1743090 TI - [Increase in the affinity of rat brain M-cholinergic receptors upon one-time administration of the cholinolytic, amizyl]. PMID- 1743091 TI - [Synergism of processes of generating active forms of oxygen and proteolysis as a possible reason for developing influenza]. PMID- 1743092 TI - [Functional significance of proliferative activity of retinal pigment epithelium cells during early postnatal development of the Syrian hamster (Cricetus auratus)]. PMID- 1743093 TI - [Comparative characteristics of neuronal activity of the frontal cortex and caudate nucleus of the monkey during realization of delayed behavior]. PMID- 1743094 TI - [Long-term results of coronary angioplasty in relation to vessel size]. AB - Repeat angiography was performed after 3-4 months in 927 of 1386 consecutive patients (67%) who had a successful percutaneous coronary angioplasty (PTCA) between 1986 and 1988. The degree of coronary artery stenosis was determined angiographically before PTCA, immediately after and 3-4 months later. Patients were assigned to one of four groups according to balloon diameter at dilatation: Group 1: 1.5-2.0 mm; group 2: 2,5 mm; group 3: 3.0 mm; group 4: 3.4-4.2 mm. Vessel wall proliferation occurred in all four groups after PTCA. In patients with angiographically demonstrated recurrence (first recurrence: 308 patients, second recurrence: 43 patients) another balloon dilatation was undertaken and a repeat angiography 3-4 months later. Long-term success rate (less than 50% stenosis) differed significantly according to the post-PTCA vessel diameter: 48% in group 1, 63% in group 2, 66% in group 3 and 80% in group 4 (analysis of variance: P less than 0.001). PTCA thus produces better long-term results in large than in small vessels. PMID- 1743095 TI - [Atraumatic Clostridium septicum infection in granulocytopenia]. AB - A fatal Clostridium septicum infection occurred in three patients. Case 1. A 55 year-old man died of septicaemia resulting from granulocytopenia of uncertain aetiology; it was associated with perforation of ileal mucosal ulcers. Autopsy revealed neutropenic enterocolitis and diffuse gas formation, especially in the brain, caused by Clostridium septicum. Case 2. A 18-year-old boy developed a caecal invagination during imipenem-induced granulocytopenia. A fulminant postoperative Clostridium septicum infection ended fatally. At autopsy many ulcers were found at the site of invagination with gas formation involving all organs. Case 3. Myonecrosis of the left arm, caused by Clostridium septicum, developed without external cause in a 12-year-old girl with congenital neutropenia. Despite aggressive surgical intervention she died of toxic shock. Autopsy revealed caecal mucosal ulcers as the portal of entry of Clostridium septicum. PMID- 1743096 TI - [Dual cause of obstructive jaundice: cholangiolithiasis and malignant choledochal stenosis]. AB - Endoscopic retrograde cholangiopancreatography in a 78-year-old woman with right sided upper abdominal pain and jaundice (total bilirubin 8.9 mg/dl) revealed two stones, of about 1 cm diameter each, in the biliary duct. They were removed after papillotomy. Because of persisting jaundice (total bilirubin 7.6 mg/dl) and a history of two years of recurrent cholecystitis a cholecystectomy was performed. At operation an advanced carcinoma of the gallbladder was discovered, with tumour compression of the extrahepatic choledochal duct. After removal of the gallbladder the stenosis was bridged with a T-drain. For permanent bile diversion of a self-expanding stent was endoscopically implanted. The patient has been symptom-free so far for 6 months. It is stressed that, especially in elderly patients, malignant choledochal stenosis must be included in the differential diagnosis of obstructive jaundice caused by stones and diagnostic procedures undertaken accordingly. PMID- 1743097 TI - [Varicosis of the great saphenous vein as a main symptom of iatrogenic arteriovenous fistula]. AB - A 22-year-old man with movement-dependent knee-joint pain was operated on for patellar chondroplasia and meniscal dysplasia after two previous arthroscopic removal of free joint bodies had failed to bring relief. A few months after the operation the same leg had become swollen with signs of venous congestion, long saphenous vein varicosity and traumatic pretibial crural ulcer. The long saphenous vein was partially excised. 18 months after the arthrotomy there was clinical and colour-Doppler evidence of an arteriovenous fistula with false aneurysm in the region of the popliteal artery as cause of the venous congestion. The ulcer healed completely after ligation of the fistula and excision of the false aneurysm. --Arterio-venous fistula should be included in the differential diagnosis as a possible cause of postoperative swelling of a limb. PMID- 1743098 TI - [Clinical aspects and diagnosis of community-acquired pneumonia]. PMID- 1743099 TI - [Prehospital thrombolysis in acute myocardial infarct]. PMID- 1743100 TI - [When will fibrinogen screening become available?]. PMID- 1743101 TI - [Endoscopy in patients with joint prostheses only under antibiotic prophylaxis?]. PMID- 1743102 TI - [Therapy of severe systemic lupus erythematosus]. PMID- 1743103 TI - [Coumarin-induced necrosis]. PMID- 1743104 TI - [Catheter ablation. Curative treatment in symptomatic Wolff-Parkinson-White syndrome]. PMID- 1743105 TI - Preoperative evaluation of patients with advanced tumors of the skull base. AB - The purpose of the pre-operative assessment in patients with advanced skull base disease, is to provide the treating physicians with as much data as possible pertaining to the patient and the disease. The meticulous analysis of this clinicoradiologic evaluation will help in planning the method and magnitude of tumor resection, and functional defect reconstruction. PMID- 1743106 TI - Radiographic evaluation of the skull base. AB - The anatomic complexities of the skull base and the variable clinical presentation of skull base tumors often precludes accurate determination of tumor boundaries by history and physical alone. Imaging, employing computed tomography (CT) and magnetic resonance imaging (MR) allows for accurate tumor mapping and planning of appropriate therapeutic intervention. Calvarium floor involvement and extracranial lesions are well delineated by CT. While multiplanar MR is unparalleled in demonstrating tumor boundaries and extension through the skull base. In order to employ these imaging modalities in an efficient way, it is important to understand the limitations and capabilities of these modalities as well as the imaging characteristics of common skull base lesions. PMID- 1743107 TI - Transsphenoidal approaches to the skull base. PMID- 1743108 TI - Transoral approaches to the skull base. PMID- 1743109 TI - Craniofacial resection. PMID- 1743110 TI - Transtemporal approaches to the skull base. AB - Transtemporal approaches to lesions of the posterior fossa and/or temporal bone afford direct access with minimal manipulation of the subdural spaces. In most instances, the primary concern is the preservation of seventh nerve integrity or restoration of seventh nerve function in the event of loss of facial nerve integrity. The transtemporal approaches afford the surgeon the ability to trace the seventh nerve from normal to diseased regions and so increased the possibility of anatomical preservation. In addition, the availability of the seventh nerve for transposition or rerouting makes nerve grafting easier in the event of seventh nerve sacrifice. Limitation of the craniectomy site within the temporal bone without violating the deep cervical musculature avoids the complication of severe postoperative headaches so frequently seen in suboccipital resections. Thorough knowledge of the temporal bone anatomy and intracranial structures is mandatory prior to utilization of this procedure. PMID- 1743111 TI - Temporal bone resection. AB - It must be emphasized that the greatest impact of survival can only be obtained through an early diagnosis and a radical treatment program. Any granulation tissue must be sent for biopsy to rule out the possibility of malignancy in the setting of chronic otitis media. Once carcinoma is diagnosed, imaging studies must be obtained to define the extent of the tumor. Under diagnosis is the rule with these malignancies. Tumors limited to the external auditory canal can be adequately resected with a lateral temporal bone resection. Extension into the middle ear and mastoid aircell systems requires either a subtotal temporal bone resection or a lateral temporal bone resection with a radical mastoidectomy and petrousectomy. The inclusion of the petrous apex with the resection, as in a temporal bone resection, does not add to survival but increases morbidity. Radical postoperative radiation therapy is essential for maximum local control and survival with these malignancies. PMID- 1743112 TI - The infratemporal fossa approach to skull base surgery. AB - The infratemporal fossa approach, in conjunction with the application of microsurgical technique and improved perioperative care, has permitted significant advances in lateral skull base surgery. The glomus jugulare tumor is the prototypical neoplasm resected by this approach, although this technique can be applied to a host of additional benign and malignant lesions of the skull base. This approach entails identification and control of the cranial nerves and great vessels in the neck, anterior transposition of the facial nerve, and infralabyrinthine petrosectomy. Intracranial tumor extension and petrous carotid artery involvement remain limiting factors. Significant morbidity, particularly neurologic deficit and hemorrhage, may occur due tot the nature and location of lateral skull base tumors. Recent advances in preoperative embolization and temporary carotid artery balloon occlusion have advanced the limits of resection via the infratemporal fossa approach. PMID- 1743113 TI - Management of high parapharyngeal space tumors. PMID- 1743114 TI - Complications of skull base surgery. AB - As skull base resections have increased in complexity and magnitude, so have the complications associated with the procedures. In this paper, we have reviewed the major complications of skull base surgery, including CSF leak, bleeding, stroke, meningitis, cranial nerve deficits and recurrent disease. This report summarizes the factors that lead to these complications, as well as measures to prevent them. We have also discussed our approach to the management of these complications, with particular emphasis on CSF leak and vagal nerve paralysis. PMID- 1743115 TI - Effect of otitis media on development: a community-based study. AB - Otitis media history until age 3 years were recorded for 233 children as part of the surveillance in a Community Program for Promotion of Growth and Development (PROD) conducted in a western neighborhood of Jerusalem. Recurrent otitis media (6 or more episodes) occurred more frequently among children who were of North African or Asian origin, of lower social class and maternal education, and whose duration of breast feeding was less than 26 weeks. Children with recurrent otitis media also failed the 7-month hearing test more frequently than other children. The mean Developmental Quotient score at 2 years and the mean Stanford Binet score at 3 years were statistically significantly lower among children with recurrent otitis media, even after controlling for maternal origin and length of breast feeding. These findings underscore the importance of early identification and early intervention for otitis media. PMID- 1743116 TI - Fetal and preterm newborn cerebral blood flow velocity. AB - Using Doppler ultrasound, cerebral blood flow velocities (CBFV) in the first month of life of normoxemic preterm infants born in the 28th gestational week with stable circulatory conditions were examined. The results were compared with fetal CBFV in the 28th to 32nd weeks of pregnancy. Peak systolic (PSV), end diastolic (EDV) and time averaged maximum velocities (TAMV) were evaluated from the Doppler shifts recorded from the middle cerebral artery (MCA). Cerebral circulatory changes in neonates in the first 4 weeks of life were much more pronounced than in fetuses at the corresponding gestational age (28-32 weeks). After the rapid increase in neonatal CBFV in the first 3 weeks of life, our results appear to indicate a stabilisation between the 3rd and 4th week (corresponding to the 32 gestational weeks). The significance of, and possible mechanisms for, these changes are discussed. PMID- 1743117 TI - Circadian rhythms in early human development. AB - The body temperature, heart rate and rest-activity cycles of 12 low-risk preterm infants (29-35 weeks) were continuously recorded in the neonatal intensive care unit over a period of 1-2 weeks. Throughout the recordings the light was on continuously, the feeding was done intra-gastrically every 2 h and the incubator temperature was constant. Under such conditions a significant circadian rhythm was found in the body temperature and heart rate of more than 50% of the infants. These findings indicate the possible existence of an endogenous circadian rhythm in early human infancy. Since lights are continuously on in the neonatal intensive care unit, this might impair the time of emergence of day-night entrainment of the biological clock in preterm infants. PMID- 1743118 TI - Detectability of auditory evoked response components in preterm infants. AB - In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants. PMID- 1743119 TI - Quantitative analysis of T and B cell subsets in healthy and sick premature infants. AB - This work proposes a serial quantitative analysis of the numbers and percentages of B and T cell subsets in 104 consecutive premature infants (PI) between birth and six months of age as compared with 21 normal term infants. First, in order to ascertain the effects of perinatal distress at birth (respiratory distress, neonatal asphyxia) on certain parameters of the immune system, the PI were divided into two groups. One comprised 36 healthy preterms, the other, 68 preterms with perinatal distress. It was then shown that healthy PI differed from full-term infants by their higher absolute numbers of T cells (CD2-positive) and helper T cell subset (CD4-positive). These increases in CD2- and CD4-positive cells correlated with gestational age (GA). An increase in B lymphocytes (CD20 positive cells) was also documented but no correlation with GA could be seen. Secondly, perinatal distress was found to be concomitant with transient decrease in percentages and absolute numbers of CD2- and CD4-positive cells, particularly in PI of less than 28 weeks of gestation. The B cells (CD20- and CD21-positive cells) were not different in absolute numbers. Respiratory distress had a more discernable effect than fetal asphyxia on the immune system. Finally, no immunological parameters tested could at any time predict the occurrence of infection in PI during the first 6 months of life. PMID- 1743120 TI - Cranial computed tomography in the under twos. AB - One hundred consecutive cranial computed tomographic scans were reviewed in children aged 0-2 years, presenting to the Royal Belfast Hospital for Sick Children. The mean age at scanning was 8.3 months and 73% of the scans were abnormal. The majority of scans were performed electively (78%). The commonest indication for a scan was seizures (31) and the diagnostic yield was highest where they were associated with other neuro-developmental symptoms. The usefulness of the CT scan was not limited to the abnormal studies but contributed to management in children with normal scans by excluding important intracranial pathology. Developmental CNS malformation (16 scans) and cerebral atrophy (15 scans) were the most frequent CT abnormalities encountered. PMID- 1743121 TI - Spontaneous chromosome fragility in chorionic villus cells. AB - Human fragile sites are only very rarely expressed spontaneously. In this paper we report the presence of non-random spontaneous chromosome lesions (CL) in chorionic villus samples and their coincidence with fragile site (FS) bands. The average number of CL was about 9% both in RPMI-1640 and in Chang media. To determine any possible influence of external factors other than culture media, the results were grouped according to age of gestation. No differences were observed among the different groups. A total of 101 chromosome lesions could be precisely identified by sequential Leishman Staining/Wright G-banding; 76.2% of them coincided with FS-bands. The most affected region was at 1q12-1q21.1 (15.8% of total CL); other FS with a clustering of breakpoints in our study were 1p36, 1q44, 2q37, 3p24, 3q27, 10q22 and 16q23. These results suggest that spontaneous expression of some FS could be a characteristic of embryonic tissues. PMID- 1743122 TI - Evaluation of endosonography in sclerotherapy of esophageal varices. AB - During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy. PMID- 1743123 TI - Guillotine needle biopsy as a supplement to endosonography in the diagnosis of gastric submucosal tumors. AB - The presumptive diagnosis of gastric submucosal tumors can be made by endoscopic ultrasonography (EUS) but histological confirmation is still required. A special guillotine biopsy device (Flexi-Temno) which enables collection of adequate submucosal samples by the endoscopic approach was therefore evaluated. After visualization by EUS the guillotine needle biopsy was performed in 21 patients with submucosal tumors of the stomach. There were 2 failures in 2 patients with leiomyomas. The diagnosis suggested by EUS was confirmed by guillotine biopsy in 17 cases. Guillotine biopsy detected 2 cases of unsuspected leiomyosarcoma which were confirmed surgically. In cases of solid submucosal tumors confirmed on EUS, the guillotine needle biopsy enables a definitive histologic diagnosis. Thus malignancies can be detected when EUS findings are not significant. PMID- 1743124 TI - Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with papillary stenosis. AB - The function of the sphincter of Oddi (SO) in patients with papillary stenosis was evaluated using endoscopic manometry to determine its possible contribution to pancreatic dysfunction. A total of 30 patients with papillary stenosis were divided into two groups according to the pattern of narrowing of the sphincter zone observed in ERCP studies: group A, a mild form, and group B, a severe form. Group C (control) comprised 12 subjects with no abnormality of the pancreas or biliary system. The SO contraction pressure was significantly higher in group A (115.1 mmHg) than in groups B (79.2) and C (91.1). The SO basal pressure in groups A (11.5 mmHg) and B (10.3) was significantly higher than in group C (5.8). The pancreatic duct pressure in group A (15.5 mmHg) was significantly higher than in group C (9.7), while group B (11.1) showed an intermediate value. The increase in pancreatic duct pressure following intravenous secretin was significantly greater in groups A and C than in B. The BT-PABA test in groups A and C revealed a normal value in contrast to group B. A significant correlation was observed between these two factors. The function of both the SO and the pancreas thus appears to be abnormal in patients with severe narrowing of the SO and papillary stenosis. PMID- 1743125 TI - The quality of gastroenterological reports based on free text dictation: an evaluation in endoscopy and ultrasonography. AB - The majority of physicians consider the use of free dictation for medical reports to be essential in many domains. One of the main criticisms of structured data entry is the possible lack of flexibility and completeness. Electronic documentation systems exist for endoscopy and ultrasonography examinations which are based on structured input as well as on free dictation. Endoscopy and ultrasonography reports based on free dictation were evaluated for omissive errors. The data evaluated was drawn from a database of 18,239 gastroscopy and 3,340 colonoscopy reports dictated by 28 physicians over 74 months, and 18,834 ultrasonography reports dictated by 37 physicians over 42 months. The error rates varied from 0% to 41.8% depending upon the particular feature and the particular examination, but were usually below 15%. The results were independent of the experience of the examiner. This study provides baseline measurements of omissive error rates for selected findings in gastrointestinal endoscopy and abdominal ultrasonography which can be used as standards for the development and evaluation of systems for collection of clinical data. PMID- 1743126 TI - The SADE system: an endoscopic database manager. AB - The development of the SADE database manager was commenced in 1985 since no commercially available systems were suited for the needs of a large endoscopy unit. Over a period of five years, this database was programmed, revised and enhanced through the joint efforts of gastroenterologists and programmers, the SADE system being implemented for daily use on 1 January 1989. The patient administration and medical record modules are fully implemented and functional, while the statistical module has only recently been finished. The present features of the system are described, and the limitations discussed. Instant report generation and direct access to previous medical data are the most immediate benefits of the system. The initial intention to have structured anamnestic data had to be modified to suit the need for flexibility and ease of free text input by the users. PMID- 1743127 TI - SADE database for endoscopic procedures: aspects of clinical use. AB - The time aspects of daily use of a clinical database system in an endoscopy department were studied. The SADE database system for endoscopic procedures was introduced for daily use at Ulleval Hospital on 1 January 1989. The average weekly programme of the endoscopy unit includes 57 gastroduodenoscopies, 23 colonoscopies and 12 ERCP/EPTs. During three consecutive weeks of the study the mean physician input time was 4 min 17 sec per patient (range 57 sec to 15 min), individual variation depending mainly on the extent of the report. Assistants spent a mean time of 4 min 23 sec for each patient. Thus, a total of 8 min 40 sec was spent for every patient seen. Endoscopic units should analyze their routines and needs before introducing an electronic data base manager. PMID- 1743128 TI - SISCOPE: a multiuser information system for gastrointestinal endoscopy. AB - SISCOPE is an integrated data management system for use in gastrointestinal endoscopy units which operates in the multiuser mode on UNIX minicomputers or MS DOS personal computers and can be used for patient bookings, endoscopic data entry and retrieval, and automatic report generation in upper gastrointestinal endoscopy, proctologic examinations, colonoscopy and peritoneoscopy. The description of endoscopic findings is remarkably detailed and data entry very rapid due to an advanced design of input screens that incorporates several recent concepts, including windows, menu bars and pull-down menus; typing is eliminated as data is entered with a mouse by pointing at options within menus. Endoscopic findings can be described under eight headings: morphology, topography, qualifiers, modifiers, signs of bleeding, endoscopic diagnosis, pathological diagnosis and etiology. Terminology is based strictly 3on the OMED system. SISCOPE also allows recording of details on endoscopic procedures, indications for the examination, preparation, premedication, complications and late entry of pathology reports. After entering all data, a report in natural language is produced automatically, the entire process taking one minute on average. Data retrieval programs give on-line access to previous examinations of a given patient and automatically generate activity reports. A formal language allows direct queries to the database and transfer of data for statistical analysis or other data processing. The system is simple to learn and use because operation is intuitive and all endoscopic techniques share the same basic menu structure and screen design. PMID- 1743129 TI - Endoscopic management of biliary hydatid disease: report on six cases. AB - Six patients with a ruptured Echinococcus liver cyst were treated by means of endoscopy. The treatment consisted of endoscopic sphincterotomy, cyst material extraction and hypotonic saline lavage via a nasobiliary catheter. In five patients successful complete endoscopic treatment was achieved, including removal of daughter cysts. In the sixth patient only partial treatment could be performed with clearance of daughter cysts since there was no communication with the main liver cyst. Follow-up ultrasonography, CT and ERCP in all patients showed complete cure and no evidence of disease recurrence in five of them. The sixth patient required surgery one month after endoscopic treatment of the acute biliary obstruction. PMID- 1743130 TI - Endoscopic sphincterotomy in the management of postoperative complications of hepatic hydatid disease. AB - The results obtained using endoscopic sphincterotomy (EST) in the management of postoperative biliary complications of hepatic hydatid disease are presented. The outcome was favourable in all eight patients treated with no associated morbidity or mortality. In three patients the clinical manifestations of cholangitis resolved, and in five of six patients the external bile fistula previously present for 26 to 68 days closed within 3 to 15 days. In one patient with a long standing fistula (5 years) the bile outflow was reduced from 600cc to 50-100cc per day. No complications due to EST were encountered. The results show that EST can be considered the treatment of choice for biliary fistulae following surgery for hepatic hydatid disease and for drainage of bile in patients with cholangitis due to hydatid disease. PMID- 1743131 TI - Role of endoscopic ultrasonography in the treatment of esophageal varices. PMID- 1743132 TI - Endoscopic sclerotherapy in 1991: still evolving. PMID- 1743133 TI - A critical look at the Sydney classification of gastritis. PMID- 1743134 TI - Endosonography of groove pancreatitis. AB - Groove pancreatitis is a rare form of chronic pancreatitis. Distinction between pancreatitis and pancreatic carcinoma is often difficult. Two cases of groove pancreatitis diagnosed by endosonography are described. A hypoechoic pattern between the duodenal wall and pancreas was clearly imaged in both patients. Narrowing of the second part of the duodenum and evidence of bile duct obstruction were also found. The endosonographic diagnosis was confirmed either by surgery or follow-up examination. PMID- 1743135 TI - An unusual case of active tuberculosis of the oesophagus in an adult. AB - A case is reported of a 56-year-old woman of Libyan origin presenting with dysphagia, retrosternal pain and weight loss. Oesophago-gastroduodenoscopy revealed an ulcerated tumor in the upper oesophagus strongly suggesting a malignancy. A positive Mendel-Mantoux test along with histological evidence of epitheloid cell granulomas and clinical findings consistent with pulmonary and lymph node tuberculosis led to the presumptive diagnosis of oesophageal tuberculosis. The diagnosis was later confirmed by positive bacteriological cultures of oesophageal biopsies and gastric washings. It is very unusual for dysphagia to be the presenting symptom of active adult tuberculosis. Oesophageal tuberculosis is extremely rare and must be distinguished predominantly from oesophageal carcinoma. PMID- 1743136 TI - Endoscopic band ligation for treatment of non-variceal upper gastrointestinal bleeding. AB - An endoscopic band ligation method was successful in achieving hemostasis in two patients who had severe coagulopathy and profuse gastrointestinal bleeding from a visible vessel in the stomach. Bleeding was not controlled by multiple epinephrine injections or BICAP electrocoagulation. The technique of band ligation was easy to perform and may provide an alternative treatment for non variceal upper gastrointestinal bleeding in selected cases. PMID- 1743137 TI - Intramural hematoma of the esophagus after variceal sclerotherapy. AB - Two patients with cirrhosis are presented who developed retrosternal pain and dysphagia immediately after sclerotherapy of esophageal varices. Extensive submucosal bleeding of the esophageal wall was demonstrated radiologically and endoscopically. Complete resolution occurred spontaneously and did not lead to residual complications such as strictures. Intramural hematoma of the esophagus is an unusual complication after endoscopic variceal sclerotherapy. PMID- 1743138 TI - Splenic injury as a complication of endoscopy: two case reports and a literature review. AB - Two cases of splenic injury - one after a difficult colonoscopy and the other after routine ERCP - are reported. Splenic injury as a complication of endoscopic procedures is relatively rare, but over the past several years this complication has been increasingly reported. Review of the literature revealed 11 cases occurring after colonoscopy and one after ERCP. Although most of the patients presented with acute abdominal symptoms, some had mild vague symptoms. In two cases the injury was overlooked entirely. Diagnosis was established at laparotomy in four cases, by CT in four, by ultrasonography in two, by chance observation in two, by angiography in one and by paracentesis in one. All patients except the most recent three reported underwent surgery, with one mortality occurring three weeks after the operation. PMID- 1743139 TI - Computer graphics simulation for teaching. PMID- 1743140 TI - Esophageal bezoar due to sucralfate. PMID- 1743141 TI - Guaiac-positive stools and ulceration of the colon associated with salmonellosis. PMID- 1743142 TI - Choledochoduodenal fistula: a rare sequel of duodenal ulcer. PMID- 1743143 TI - Duplication of the cystic duct detected by endoscopic retrograde cholangiopancreatography. PMID- 1743144 TI - Deleterious circulation of intestinal contents through the biliary tract after cholecystojejunostomy. PMID- 1743145 TI - Association of annular pancreas and pancreas divisum. PMID- 1743146 TI - Increase of methylguanidine and guanidinoacetic acid in the brain of amygdala kindled rats. AB - Guanidino compounds are intrinsic chemoconvulsants. We investigated the regional and time-dependent changes of these compounds in the amygdala (AM) of kindled rats versus electroconvulsive shock (ECS) seizures using high-performance liquid chromatography (HPLC). Twenty-eight days after the last AM-kindled seizure, guanidinoacetic acid (GAA) and methylguanidine (MG) levels were significantly increased in the bilateral AM as compared with those of control rats, which had been implanted with electrodes but were not stimulated. Both compounds, however, tended to decrease in the bilateral AM after ECS seizure. In addition, we measured these compounds after induction of one afterdischarge (AD) in the AM. These compounds increased significantly 7 days after AD was induced in the ipsilateral AM. We suggest that the increase of these compounds is coincident with AD generation and specific to AM kindling and the kindled state. PMID- 1743147 TI - Interictal behavioral alterations and cerebrospinal fluid amino acid changes in a chronic seizure model of temporal lobe epilepsy. AB - This study extends our previous work in which we described the presence of an interictal behavioral disturbance in a chronic animal model of temporal lobe epilepsy (TLE). In this study, we investigated the cerebrospinal fluid (CSF) neurotransmitter changes underlying the development of chronic recurrent seizures of temporal lobe origin and interictal behavioral disturbance in cats made epileptic after intrahippocampal injection of kainic acid (KA). Using high performance liquid chromatography, we measured 22 putative neurotransmitter amino acids. After intrahippocampal KA injection, cats developed an initial acute period of intense seizure activity. Cisternal CSF amino acids, which were repeatedly sampled during the acute period through a permanent indwelling cannula, were unchanged apart from a mild elevation in CSF alanine. The high level seizure activity gradually decreased, and cats entered a chronic epileptic period characterized by recurrent yet intermittent temporal lobe seizures. CSF GABA levels during the chronic epileptic period were significantly decreased. In contrast, CSF levels of other amino acids--alanine, tyrosine, taurine, aspartic acid, and glutamic acid--did not change significantly. Behavioral testing also showed a heightened interictal defensive reactivity during the chronic epileptic period. To the extent that CSF GABA concentration reflects brain GABA concentration, this study suggests that a decrease in brain GABA may contribute both to the epilepsy and interictal emotional lability of animals with a chronic seizure disorder of temporal lobe origin. PMID- 1743148 TI - Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. AB - Structural damage of the human brain (perinatal damage, cerebral trauma, head injury, cerebrovascular and degenerative diseases, intracranial tumor, metabolic diseases, toxins, drug-induced seizures) may lead to chronic epilepsy in survivors. Epidemiologic analyses show that a considerable time-delay occurs between the exposure of the brain to injury and the appearance of seizures. Such seizures are usually partial or mixed, may develop at any age, and are difficult to treat. In rats subjected to structural damage of the brain induced by sustained convulsions triggered by systemic administration of the cholinergic agent pilocarpine, spontaneous seizures may develop after a mean latency of 14-15 days. The mean frequency of spontaneous recurrent convulsions remains constant for several months. Evolution of these convulsions proceeds through several electrographic and behavioral stages resembling kindling. Kindling may be otherwise induced in rodents by repeated systemic administration of convulsants or by repeated electrical stimulation of sensitive brain regions. These observations demonstrate that structural damage of the brain may lead to spontaneously recurrent convulsions (chronic epilepsy) in rats and that kindling may be involved in the evolution of such a condition. This finding suggests that kindling mechanisms underlie the development of epileptic foci from structural brain lesions. Such mechanisms may be involved in the etiology of some forms of epilepsy in humans. PMID- 1743149 TI - Electroencephalographic characteristics of audiogenic seizures induced in metaphit-treated small rodents. AB - Adult male mice, rats, and guinea pigs were subjected to intense sound stimulation of an electric bell (100 dB, 12 kHz for 60 s) after a single intraperitoneal (i.p.) injection of metaphit (1-(1-(3 isothiocyanatophenyl) cyclohexyl)piperidine) (50 mg/kg). When the animals were tested 24 h after administration of metaphit, audiogenic seizures were observed. None of the control saline-injected animals had convulsions. EEG recordings demonstrated the appearance of paroxysmal activity and spike-wave complexes in the trace from cortical and hippocampal electrodes, with frequency and amplitude increasing with time. Behaviorally, myoclonic jerks of facial muscles, ears, and neck appeared, but no correlation was noted between EEG and the motor phenomena. Auditory stimulation was necessary to elicit the full-blown sequence of seizure responses consisting of wild running followed by clonic and then tonic extension. At the time of seizures, repetitive high-amplitude spikes and waves appeared in the EEG, followed by profound EEG and behavioral depression. None of the animals died during or immediately after seizures. The seizure response to sound stimulation of mice, rats, and guinea pigs was phenomenologically similar, with minor differences in quantitative pattern of convulsive components, which suggests that all three animal species share the common property of extreme susceptibility to audiogenic stimulation caused by metaphit administration. PMID- 1743150 TI - Study of the prevalence of epilepsy among schoolchildren in Valladolid, Spain. AB - A population study was performed to estimate the prevalence of epilepsy in the juvenile population of Valladolid, Spain. Using a mixed questionnaire (postal domiciliary), we studied a sample of 5,100 primary school pupils (aged between 6 and 14 years) and 48 pupils receiving state-run special education. We also identified all the students receiving private special education and from specific special education centers belonging to the same age group (90 and 145, respectively). The prevalence of epilepsy in the school age population on December 1, 1987 was estimated at 5.72/1,000 inhabitants. Our results are comparable to those of other studies in Western countries. PMID- 1743151 TI - Images of epilepsy in literature. AB - Literature primarily reflects and affirms existing attitudes and conceptions regarding the epilepsy population. In the fiction of many nations for many centuries, individuals with epilepsy have emerged as evil or saintly, as geniuses, or as objects of pity whose lives were not worth living. The character who had epilepsy was outside the realm of personal identification--too far beneath or too far above us. Nevertheless, there were exceptions. Literature, as well as film and television, especially in the last 2 decades, has shown both readers and audiences that there are human beings who have epilepsy (rather than who are epileptics). These human beings are simply part of the continuum of what we know as normal: no more and no less than merely human. PMID- 1743152 TI - Joan of Arc. AB - For centuries, romantics have praised and historians and scientists debated the mystery of Joan of Arc's exceptional achievements. How could an uneducated farmer's daughter, raised in harsh isolation in a remote village in medieval France, have found the strength and resolution to alter the course of history? Hypotheses have ranged from miraculous intervention to creative psychopathy. We suggest, based on her own words and the contemporary descriptions of observers, that the source of her visions and convictions was in part ecstatic epileptic auras and that she joins the host of creative religious thinkers suspected or known to have epilepsy, from St. Paul and Mohammed to Dostoevsky, who have changed western civilization. PMID- 1743153 TI - Cerebrospinal fluid lactate levels and prognosis in status epilepticus. AB - Despite recent advances in the treatment of status epilepticus (SE), the mortality and morbidity associated with this condition remains high. Although the reasons for this excessive mortality are not known, several factors are suspected, including cerebral ischemia, cardiovascular collapse, toxic stimulation by neurotransmitters and hormones, or toxic products of intermediary metabolism. Cerebral lactic acidosis can cause cortical injury and has been shown to occur with seizures in experimental animals and in a limited number of human studies. We determined cerebrospinal fluid (CSF) and plasma lactate in 29 patients with generalized SE of diverse etiology. CSF was obtained within 12 h of termination of clinical seizure activity. The mean CSF lactate for all SE patients was elevated (3.74 +/- 0.31 mM) as compared with that of normal controls (1.60 +/- 0.10 mM) from non-neurologic patients undergoing spinal anesthesia. In patients who died or had a poor neurologic recovery, CSF lactate level was 5.36 +/- 0.58 mM (9 patients), whereas in 20 patients who showed good recovery CSF lactate level was 3.01 +/- 0.22 mM (p less than 0.005). The results demonstrate that SE causes a significant increase in CSF lactate and suggest that the magnitude of lactate elevation may serve as a predictive indicator of morbidity and mortality. PMID- 1743154 TI - Role of the frontal lobes in the propagation of mesial temporal lobe seizures. AB - The depth ictal electroencephalographic (EEG) propagation sequence accompanying 78 complex partial seizures of mesial temporal origin was reviewed in 24 patients (15 from the University of Pittsburgh Epilepsy Center and 9 from UCLA). All patients were monitored with bilateral mesial frontal and mesial temporal depth electrodes and later received anterior temporal lobectomy. Ictal EEG records were categorized according to sequence of spread from the temporal focus to the other regions. Although propagation patterns varied both within and between patients, certain features were notable: (a) It was very common for seizure activity to spread initially to the ipsilateral frontal lobe (observed in 22 of 24 patients). (b) The most common mode of spread (15 of 24 patients) was initiating temporal lobe----ipsilateral frontal lobe----contralateral frontal lobe----contralateral temporal lobe. (c) Occasionally, seizure discharges invaded the frontal lobes but failed to invade the contralateral temporal lobe (2 of 24 patients). (d) Seizure activity occasionally invaded the contralateral temporal lobe prior to invading the frontal lobes (2 of 24 patients). Other notable features included (i) a clear tendency for mesial temporal seizure discharges initially to invade orbitofrontal (as opposed to anterior cingulate) cortex and (ii) the emergence of a period of clear asymmetry in the frontal lobes during which high-amplitude, rapid discharges were present on the side ipsilateral to the initiating temporal lobe. These results suggest that the prefrontal region, especially the orbitofrontal cortex, is strongly influenced by mesial temporal ictal activity. This region appears to be frequently involved in the propagation of seizures initiated in the mesial temporal lobe and may play a role in the interhemispheric propagation of mesial temporal seizures. PMID- 1743155 TI - Analysis of foramen ovale electrode-recorded seizures and correlation with outcome following amygdalohippocampectomy. AB - We report a detailed electroclinical analysis of 320 seizures recorded by foramen ovale electrodes in 77 potential candidates for selective temporal lobe surgery because of antiepileptic drug-resistant seizures. The exact localization of the origin of seizure discharges, the electroencephalographic (EEG) seizure onset patterns, transhemispheric propagation, propagation time, duration of discharge, laterality of discharge termination, postictal focal slowing, correspondence between foramen ovale recordings and the scalp EEG, and the influence of antiepileptic drug modifications were studied and correlated with the clinical seizure semiology and with postoperative outcome following selective amygdalohippocampectomy. In general, the foramen ovale electrode technique provided good neurophysiological information in candidates for selective amygdalohippocampectomy. The following ictal signs predicted a good surgical outcome: (a) unilateral and anterior mediobasal temporal lobe seizure onset, (b) short seizure duration, (c) no or infrequent contralateral seizure discharge propagation, and (d) if propagation to the contralateral mediobasal temporal lobe occurred, the postoperative outcome was better the later the contralateral mediobasal temporal lobe was affected. Postoperative outcome was also better the less frequently contralateral interictal spikes occurred. No direct predictive value could be attributed to the presence of an initial arrest reaction. PMID- 1743156 TI - Natural history of recurrent seizures after resective surgery for epilepsy. AB - Seizures persist or recur in 20-60% of patients after resective surgery for intractable partial epilepsy. Further information about the natural course of these seizures is lacking in the literature. During one decade of epilepsy surgery at a single institution, we identified 72 patients with recurrent postoperative seizures after resective procedures for epilepsy. Prospectively compiled seizure diaries, hospital records, and outpatient office records were reviewed and supplemented by telephone communications to assess subsequent seizure frequency. Follow-up data was available ranging from 6 months to 7 years 5 months (mean 3 years 5 months). The likelihood of persistent seizures and recurrent intractability was examined with life-tables. Seizures recurred within the first postoperative year in 86% of patients and were similar to preoperative events in 74% of patients. After the first seizure recurrence, there was 80% likelihood of persistent seizures in the next 6 years and 40% likelihood of intractability (more than one seizure a month despite optimal medical therapy). The interval until recurrence within the first postoperative year did not affect the likelihood of subsequent seizures or intractability. Late seizure recurrence (after the first year) was not associated with any instances of subsequent intractability. Recurrent seizures after extratemporal resections were more likely to become persistent and intractable than seizures recurring after temporal resections. This information provides rational prognostication and assists in counseling patients with recurrent seizures after resective surgery for intractable epilepsy. PMID- 1743157 TI - Intracarotid amobarbital procedure: I. Prediction of decreased modality-specific memory scores after temporal lobectomy. AB - To assess predictive value of the intracarotid amobarbital procedure (IAP) for decreased postoperative modality-specific memory, we studied 37 temporal lobectomy patients with intractable partial epilepsy who were selected for operation independent of preoperative IAP findings. When ipsilateral IAP failure was defined by an absolute method as a retention score less than 67%, the results were not associated with decreased modality-specific memory after operation. When ipsilateral IAP failure was defined by a comparative method as a retention score at least 20% lower after ipsilateral than contralateral injection, the results showed greater differences between groups, but differences still did not achieve statistical significance. Four left-resection patients who failed the ipsilateral IAP had a median postoperative change in the Wechsler Memory Scale-Revised (WMS R) Verbal Memory Index score of -14%, whereas 16 left-resection patients who passed the ipsilateral IAP had a mean postoperative change in the WMS-R Verbal Memory Index score of -7.5% (p = 0.12). These results suggested that the IAP interpreted comparatively may be a helpful adjunctive test in assessment of relative risk for modality-specific memory dysfunction after temporal lobectomy, but larger series of operated patients are needed to confirm this possibility. In this series, complete amnesia was not noted after ipsilateral injection, even in patients with postoperative modality-specific memory decline. PMID- 1743158 TI - Intracarotid amobarbital procedure: II. Lateralizing value in evaluation for temporal lobectomy. AB - The intracarotid amobarbital procedure (IAP) was assessed for lateralizing value in 37 patients who later had temporal lobectomy for intractable epilepsy. Among patients who failed IAP memory testing on one side (defined as a retention score for test items at least 20% lower on one side than the other), significantly more patients failed the injection contralateral (16 of 20, 80%) than ipsilateral (4 of 20, 20%) to the side of later resection (p = 0.008). In addition, preoperative EEG evidence of bilateral temporal epileptogenicity was significantly more frequent among patients who failed the ipsilateral IAP injection (2 of 4, 50%) than among patients who passed the ipsilateral IAP injection (2 of 33, 6%) (p = 0.050). Finally, failure of the contralateral IAP injection involved significantly more severe amnesia for test items (median retention score 25%) than did failure of the ipsilateral injection (median retention score 59%) (p = 0.047). Profoundly low retention scores less than 33% occurred only with contralateral injection. These findings suggest that the IAP has some adjunctive lateralizing value for the epileptogenic hemisphere in patients with temporal lobe epilepsy, especially when the retention score with one injection is profoundly low. PMID- 1743159 TI - Computerized analysis of EEG background activity in epileptic patients. AB - Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity. PMID- 1743160 TI - Transient global amnesia as a postictal state from recurrent partial seizures. AB - A 60-year-old patient had a 3-year history of recurrent memory disturbances. The video electroencephalographic (EEG) recording of one attack showed that the amnesic state, which clinically resembled transient global amnesia, was characterized by a normal EEG tracing followed by electroclinical complex partial seizures. We suggest that "epileptic" transient global amnesia is postictal in nature. PMID- 1743161 TI - Speech during partial seizures: intracranial EEG correlates. AB - Vocalization during a seizure may help predict the location of seizure onset or identify structures ultimately involved in the seizure. Spontaneous vocalization during seizures was studied retrospectively in 22 patients with refractory complex partial seizures evaluated with bilateral intracranial electrodes. Of 22 patients, 12 vocalized during seizures. Seizures were as likely to originate from language-dominant (6/12) as from language-nondominant mesial temporal cortex (6/12). Fluent speech frequently occurred as seizure activity was recorded from language-dominant temporal lobe neocortex (6/12 seizures). Of the patients with well-localized seizure onsets who did not speak (6/10), seizures arose from both language-dominant and -nondominant mesial temporal cortex. We conclude that the presence or absence of vocalizations during a seizure does not reliably indicate the anatomic regions in which the seizure begins or spreads. PMID- 1743162 TI - Chronic, habitual cocaine abuse and kindling-induced epilepsy: a case report. AB - Kindling has been suggested as a possible mechanism for cocaine-induced seizures in chronic cocaine abusers, even though no convincing examples have been reported. We report a 37-year-old woman who initially experienced generalized tonic-clonic seizures (GTC) only immediately after "crack" use. She had a normal examination, negative family or past history for seizures, and normal cranial computed tomography and EEG. After she had abused cocaine almost daily for 2 years, her EEG demonstrated bitemporal slowing with independent spikes, and seizures were no longer temporally associated with acute cocaine use. Thereafter, despite complete abstinence from cocaine and treatment with phenytoin, she continued to experience four to six GTC a month. In light of the lack of other predisposing factors for epilepsy, this case may represent an example of cocaine induced kindling in humans. PMID- 1743163 TI - Longitudinal EEG studies in a kindred with Lafora disease. AB - We reviewed 18 EEG studies in four members of a family with the Lafora form of progressive myoclonic epilepsy. Each patient was the product of a consanguinous marriage and presented as a teenager with progressive seizures, myoclonus, dementia, and ataxia, and had biopsy proven disease. The EEG early in Lafora disease has spike-wave activity resembling that seen in a primary generalized epilepsy; the background slowing is more typical of a secondary generalized epilepsy. With disease progression, there is increased epileptiform activity, and a striking change in the spike-wave complexes, with a marked increase in frequency up to 6-12 Hz, and many more short duration polyspike components. Unlike some other forms of secondarily generalized epilepsy, the EEG in Lafora disease is distinguished by an increased frequency of the spike-wave complexes with disease progression. PMID- 1743164 TI - Clinical and neurophysiological development of Unverricht-Lundborg disease in four Swedish siblings. AB - Four siblings aged 12-18 years with progressive myoclonus epilepsy demonstrated a subclinical stage at the age of 9-11 years, with visual blackouts and polyspike electroencephalographic (EEG) activity on photic stimulation, an early myoclonic stage at the age of 12-15 years, with increasing segmental, stimulus-sensitive myoclonus, occasional nocturnal buildup myoclonic "cascade" seizures, slowing of EEG alpha-activity, episodic 4-6 Hz bilateral sharp waves and polyspikes with myoclonias on photic stimulation, and a disabling myoclonic stage at the age of 16-18 years, with periodic generalized myoclonias, nocturnal myoclonic "cascade" seizures, ataxia, dysarthria, mental changes, intermittent wheelchair dependency, and continuous EEG slow waves with polyspikes and intense myoclonias on photic stimulation. One of the siblings died at the age of 18 years with no apparent cause of death. Treatment with antiepileptic drugs other than valproate may have contributed but none of the siblings were ever treated with phenytoin. Extensive clinical and laboratory investigations revealed no abnormalities and excluded other known possible causes of progressive myoclonus epilepsy. The diagnosis was consistent with Unverricht-Lundborg disease and rested on typical age of onset, clinical signs, EEG, and evoked response abnormalities. Buildup myoclonic seizures are typical in advanced stages of Unverricht-Lundborg disease. We have labeled these myoclonic "cascade" seizures. A typical seizure was studied with video-EEG and cardiorespiratory monitoring. Characteristics revealed were onset with continuous arrhythmic myoclonic jerks followed by intense rhythmic myoclonus with increasing muscle tone that successively reduced the amplitude of the jerks. The EEG during the whole seizure showed intense polyspike activity. Obstructive apnea was seen at the peak of the seizure. There were no cardiac dysrhythmias. Consciousness was normal or only slightly impaired. Postictal drowsiness was not observed. Myoclonic "cascade" seizures are easily confused with generalized tonic clonic seizures. PMID- 1743165 TI - Epileptic nystagmus. AB - Two cases of epileptic nystagmus (EN) are described. The first patient had no history of seizures and experienced attacks of EN associated with oscillopsia and followed by horizontal diplopia and esotropia. These episodes could be triggered by certain visual stimuli and ocular pressure. The second patient had a history of generalized tonic-clonic seizures. He displayed episodes of EN that changed direction in the course of the attacks simultaneously with a shift of the EEG discharge from one occipital region to the other. Cortical blindness followed postictally. On recovery from the postictal state, both patients were neurologically normal. With standard electrodes, the EEG seizures associated with EN involved the occipital, posterotemporal, and parietal areas of the scalp contralateral to the fast phase of the nystagmus. In the first patient, use of supplementary scalp electrodes further localized the seizures to an anterior occipital site intermediate between standard occipital and posterotemporal electrodes. Thirty-six previously reported cases of EN were associated with partial seizures. Horizontal EN most commonly results from seizure activity involving the occipital cortex, although participation of adjoining portions of the parietal and temporal cortexes is possible. PMID- 1743166 TI - Epilepsy: diagnostic and treatment strategies for the next decade. Tenth Annual Merritt-Putnam Symposium. November 15, 1990, San Diego, California. Proceedings. PMID- 1743167 TI - Do seizures cause brain damage? AB - Children with epilepsy are at significant risk for cognitive impairment and behavioral abnormalities. In most children with epilepsy, the likely reason for cognitive impairment is the underlying pathology responsible for the seizures. However, there is considerable controversy about whether seizures per se can cause brain damage or increase subsequent susceptibility to seizure. Although some longitudinal studies have related a decline in intellectual abilities to continued seizures, other studies indicate that treatment with antiepileptic drugs or progression of the encephalopathic process is responsible for the decline. Both clinical and animal studies have focused on the long-term effects of seizures on the developing brain. Whereas prolonged seizures may cause permanent neurologic sequelae in the mature animal, the immature brain may be more resistant to the long-term sequelae of seizures. PMID- 1743168 TI - Localization of partial epilepsy using magnetic and electric measurements. AB - Dipole methods applied to brain electric and magnetic fields have made several significant advances in investigation of epilepsy and sensorimotor cortex. The magnetoencephalogram (MEG) and the MEG-electroencephalogram (EEG) combination have contributed substantially. The MEG-EEG combination has shown a mean accuracy of somatosensory evoked response (SER) localization of the central fissure similar to electrocorticography (ECoG), resolution of ambiguity in ECoG of alternative configurations of hand sensorimotor cortex, and resolution of ambiguity of the causes of the difference between EEG and ECoG map patterns. MEG has shown simple dipolar maps of the temporal lobe interictal spike, localization estimates with about 6 mm error, and spatial separation of propagating multiple sources. MEG and EEG have shown a new neocortical propagation pathway in the temporal lobe, noninvasive estimates of the area of the spike focus, and complementary detection sensitivity. Application of spatiotemporal multiple dipole modeling in the simplest field using MEG has given a realistic quantification of spike zones. MEG and EEG have shown simple dipolar patterns for seizure origin, suggesting focality of some frontal seizures, and appears to increase EEG utility. Improved accuracy may result from a combined methodology including MEG and EEG. Dipole methods have potential utility as a noninvasive diagnostic procedure in epilepsy. PMID- 1743169 TI - Functional anatomy: a challenge for the decade of the brain. AB - At the beginning of the "Decade of the Brain," a number of aims for epilepsy research can be identified. These range from fundamental questions about the mechanisms of seizure etiology to the ways that seizures disturb brain function and structure. Information from such research will help in the development of new treatment and rehabilitative strategies for patients with epilepsy. Current tools from molecular biology have greatly expanded the promise and challenges for epilepsy research. As these investigative efforts are undertaken, however, it is important to recall the biological environment in which epilepsy occurs. Three major axes can be identified: the organizational axis (spanning from molecules through synapses to neuronal circuits to behavior), the time axis (relating to the chronobiology of epilepsy and diversities of seizure expression as a function of age), and the functional-anatomy axis (relating to the rich heterogeneity of the brain). Focusing on functional anatomy, certain principles can be developed from work with experimental models of seizures in the hippocampus and related structures. Three levels of functional anatomy are examined--network, local circuit, and individual neuron. This information can serve as a basis for directing epilepsy research in the future. PMID- 1743170 TI - Localization of lesions by neuropsychological testing. AB - Neuropsychological evaluation differs from other methods used to localize cerebral lesions in that it analyzes cognitive function. Tests sample widely among cognitive abilities, contrasting language proficiency with visuospatial skills. A thorough assessment of memory is crucial in the investigation because of the prominence of the temporal lobes in epileptogenesis and their importance in memory. Different aspects of learning and memory are tested, and measures sensitive to hippocampal function should be included. Patients who will undergo elective surgery may also undergo intracarotid sodium amobarbital tests, which provide additional information about the integrity of each hippocampal region. Appraisal of frontal-lobe function is another important part of neuropsychological evaluation. A growing number and variety of neuropsychological tests have proven to be sensitive to lesions in this large and complex cortical area. Frontal-lobe function could be expected to vary according to the function of subregions within the frontal lobes, and some tests appear to be sensitive to specific regions. PMID- 1743171 TI - Pharmacokinetic pitfalls of present antiepileptic medications. AB - Some patients fail to respond to antiepileptic drugs (AEDs) or their response varies over time. Unexpected fluctuations in AED concentrations can cause loss of seizure control or side effects. Recent advances in AED clinical pharmacology have characterized a number of factors that alter AED concentrations. Storage of carbamazepine (CBZ) and phenytoin (PHT) formulations in hot, humid conditions alters the dosage form and reduces bioavailability up to 50%. Diurnal changes in gastrointestinal physiology affect disintegration of valproate (VPA) enteric coated tablets, reducing nighttime drug concentrations 30 to 40% compared with daytime values. Drug-drug interactions or pathophysiologic conditions (e.g., hypoalbuminemia) may displace AEDs from protein-binding sites reducing total but not unbound drug concentrations decrease. VPA not only displaces PHT from protein binding sites but inhibits its metabolism, causing a decrease in total concentration and an increase in the unbound concentration, occasionally necessitating a reduction in PHT dosage. Alterations in drug metabolism can cause fluctuations in the concentrations of AEDs and active metabolites. Enzyme inhibitors such as cimetidine or VPA can increase concentrations of both CBZ and CBZ epoxide (CBZE). Enzyme inducers such as ethanol, PHT, CBZ, and phenobarbital accelerate the metabolism of other AEDs. Some forms of physiologic stress increase binding to alpha 1-acid glycoprotein (AAG), which is stimulated within hours of a myocardial infarction or major surgery. Total CBZ and CBZE, both of which bind to AAG, increase over the same period. Stress may also activate hepatic drug metabolism. Unbound PHT clearance increases 7 to 21 days following head trauma, necessitating larger maintenance doses. Age greater than 65 years is associated with decreases in protein binding and drug clearance and longer elimination half-lives. In elderly patients, AED dosage may need to be reduced and the dosing interval extended. Knowledge of these factors permits prospective assessment of risk and the design of treatment plans that minimize fluctuations in response. PMID- 1743172 TI - New pharmacokinetic methods for the study of antiepileptic medications of the 1990s. AB - New methods that will be useful in the study of the pharmacokinetics of both new and established antiepileptic drugs include stable-isotope tracer techniques for studies of absorption, elimination, and drug interactions; the microperfusion technique and the staggered stable-isotope administration technique for the study of distribution; and the correction of trough drug serum concentration values to mean serum concentration values. New pharmacokinetic methods for a study of drugs with new and unique properties include a double stable-isotope technique to deal with the unique pharmacokinetic properties of prodrugs and techniques for describing the biologic half-life of drugs that have a high affinity for active sites. PMID- 1743173 TI - Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. AB - Rare, serious adverse effects of antiepileptic drugs (AEDs) include hepatotoxicity and bone marrow suppression. Current management includes routine laboratory monitoring during therapy with AEDs, a practice, however, that is controversial, as some clinicians believe that such monitoring is ineffective and that clinical monitoring is sufficient. Unfortunately, routine laboratory monitoring cannot predict acute idiosyncratic drug reactions, which will remain unpreventable until specific markers are available to identify susceptible patients. Nevertheless, routine laboratory monitoring may be helpful for early detection of chronic adverse reactions such as subclinical hepatotoxicity, leukopenia, or thrombocytopenia, which are usually mild and clinically insignificant but are occasionally more severe. Routine liver function tests may be especially important during valproate therapy because pathologic data suggest that some cases of valproate (VPA)-induced hepatic failure are the result of chronic liver damage and cirrhosis. Although levels of hepatic enzymes may be elevated during an early reversible stage of VPA toxicity, by the time clinical symptoms develop, hepatic failure may be irreversible. PMID- 1743174 TI - Can humans think? The Ergonomics Society Lecture 1991. AB - For many years, computer scientists have been concerned with whether computers can think. Considerable thought, therefore, goes into designing 'thinking' computer systems and into wondering whether they really can think, or just pretend to. On the other hand, it is 'obvious' that humans can think, and therefore little thought has gone into the related question, 'Can humans think?' This paper explores the ergonomic implications of the affirmative answer. Computers get better treatment than humans, yet humans are more than machines. However, not only do designers seem to forget this, but they do not even treat users with the same respect as they would a machine. PMID- 1743175 TI - The effect of the size of one and two traffic signs on two measures of perceptual performance. AB - A large object can delay the perception of a small object, which hints that the use of larger objects in general and larger traffic signs in particular may be counterproductive. The present study employed either one traffic sign or two contiguous traffic signs on a post in a photograph of a road scene. Identification of a small target sign was not slower when a second sign was contiguous than when there was only the one small target sign, regardless of whether the contiguous sign was large or small. Furthermore, when a counting task was used with the same stimuli, a large sign accelerated the response to two-sign stimuli, again regardless of the contiguous sign's size. In addition, the response to two-sign stimuli was not slower than the response to one-sign stimuli. The large small comparisons of both experiments reduce the concern that employing a large traffic sign will delay the perception of a second contiguous sign. Moreover, the one-two comparisons of both experiments imply that employing two contiguous signs will not delay the perception of a sign, despite widespread evidence that a nearby object will delay the perception of a target object. PMID- 1743176 TI - Effects of vertical vibration on passenger activities: writing and drinking. AB - Two laboratory studies have investigated how handwriting ability and holding a cup of liquid depend on the characteristics of whole-body vertical vibration. The effects of vibration magnitude (0.16 to 2.5 ms-2 r.m.s.), vibration frequency (0.5 to 10 Hz), and vibration duration (2 cycles to 10 s) on handwriting were studied with 20 subjects. Subjects were asked to copy letters of the alphabet by writing on a hand-held surface. Writing speed decreased and subjective ratings of writing difficulty increased with increasing vibration magnitude, particularly in the frequency range 4 to 8 Hz. Writing difficulty also increased with increasing duration of vibration. A 10 s exposure to 5 Hz vibration at 2.0 ms-2 r.m.s. resulted in subjective estimates corresponding to 'extremely difficult'. The effects of vibration magnitude (0.63 to 1.6 ms-2 r.m.s.), vibration frequency (0.5 to 10 Hz), and vibration duration (2 cycles to 10 s) on the spilling of liquid from a hand-held cup were also investigated in a group of 20 subjects. The probability of spilling the liquid, the quantity of liquid spilt, and subject's estimates of the probability of spillage were determined for all conditions. Greatest interference with the task occurred at 4 Hz, with the lowest vibration magnitude (0.63 ms-2 r.m.s.) causing measured and estimated spillage probabilities of approximately 85%. The interference was much less at other frequencies, with 0.63 ms-2 r.m.s. causing less than 10% measured probability of spillage below 3 Hz and above 5 Hz. The estimated probability of spillage was generally greater than the observed probability of spillage when the spillage probability was low, but less than the observed probability when the spillage probability was high. Increasing the duration of vibration increased the probability of spillage, and also increased the volume of liquid spilt. PMID- 1743177 TI - Workload and musculoskeletal problems: a comparison between welders and office clerks (with reference also to fishermen). AB - Previous studies have shown that subjective as well as clinical shoulder signs and symptoms are more common among welders than among office clerks. In the present study we wished to further evaluate the influence of different jobs on musculoskeletal problems, as well as the relationship between objective signs and subjective symptoms. This study confirmed that symptoms and signs from the shoulder were more common among the welders, who also had more subjective symptoms and clinical signs from other parts of the musculoskeletal system. Range of motion in different joint systems was, however, similar in the two groups except in external rotation of the shoulder, where welders had a more limited range. The degree of co-existence of subjective symptoms and clinical signs differed between different parts of the musculoskeletal system and was low particularly in the low back, hips, and ankles. This indicates low validity of many common clinical methods for determining musculoskeletal dysfunction. General health was good in both vocational groups and isometric strength for the welders was intermediate between that of office clerks (who had lower strength) and that of fishermen (who had higher strength, as disclosed in a previous investigation). To a similar degree welders and fishermen also had objective signs from most parts of the musculoskeletal system, whereas subjective symptoms from some parts of the body and medical consultations due to these problems were more common among welders. Atrophied shoulder muscles were more common among welders than among fishermen, whereas crepitations in the shoulder tended to be more common among the fishermen. This indicates that heavy dynamic work and prolonged static work may both induce shoulder injuries, but of different types. PMID- 1743178 TI - The design of manual handling tasks: revised tables of maximum acceptable weights and forces. AB - Four new manual handling experiments are reviewed. The experiment used male and female subjects to study lifting, lowering, pushing, pulling, and carrying tasks. Each experiment used a psychophysical methodology with measurements of oxygen consumption, heart rate, and anthropometric characteristics. Independent variables included task frequency, distance, height and duration; object size and handles; extended horizontal reach; and combination tasks. The results of the four experiments were integrated with the results of seven similar experiments published previously by this laboratory. The integrated data were used to revise maximum acceptable weights and forces originally published in 1978. The revised tables are presented and compared with the original tables. PMID- 1743179 TI - The objective measurement of pain using a motor-performance task. AB - An objective method for measuring endogenous pain in the wrist which originates in cervicobrachial disorders was improved. The method employed the plate-pushing task, which was reported previously (Taniguchi and Satow 1988a, b). The first improvement was achieved by introducing a load to be placed on the wrist while subjects were pushing the plate. In this way, it became easier to induce pain caused by disorders in the wrist. Another improvement was a new procedure by which a subject was told to change her pressure against a balance as instructed. This made it possible to identify the degree of pressure exerted which produce pain. Effects of dominance of hands, and of ordering the trials so as to begin with the dominant hand and switch to non-dominant, or vice versa in the tests were also examined, but were found to be not significant. Finally, the new method proved to be highly useful as an objective method for measuring pain of this sort because the method could produce very similar conditions to those associated with ordinary pain causing motion. PMID- 1743180 TI - The effects of alcohol on learning as a function of drinking habits. AB - Thirty-six subjects were categorized as light social drinkers (LSD) and 36 as heavy social drinkers (HSD) on the basis of both biological criteria, gamma glutamyl transferase (GGT) and the mean corpuscular volume (MCV) and by self reports of drinking habits. This study examined the effects of alcohol (0.7 ml/kg) and of noise (75 dB(A] on learning and performance, in choice RT and in immediate memory tasks. Each subject was tested in two consecutive sessions (the time factor) under one of the following experimental conditions: (a) silence + placebo; (b) silence + alcohol; (c) noise + placebo; and (d) noise + alcohol. On immediate memory, there was a strong effect of time which interacted with 'drinker' category, suggesting that HSD subjects learn less rapidly than LSD. Time interacted also with state (sober or intoxicated), showing that learning might be impaired even by a moderate dose of alcohol. On the reaction time task no main effects were found but the time X drinker category interaction was significant; in session 1 LSD's RT were shorter than those of HSD. It is suggested that regular heavy drinking might affect the learning abilities of those who are not yet labelled as alcoholics. PMID- 1743181 TI - Amygdaloid kindling during wakefulness and paradoxical sleep in the cat. 2. Sleep organization changes produced by kindling development. AB - The effect of daily electrical amygdaloid stimulation (kindling, K) during waking (W-K) and paradoxical sleep (PS-K) on sleep organization was tested in 2 groups of chronically implanted adult male cats. Animals were stimulated 3 h after the 8 h sleep recordings were begun. Percentage, total time, and mean duration and number of episodes of W, slow wave sleep I and II, and PS stages were determined. Also, the mean interval of occurrence and hourly accumulation of PS were assessed. Recordings were performed before, throughout, and immediately after kindling and 2 months after the last recorded kindled seizures. Analysis of total recording time demonstrated that in both W-K and PS-K animals the kindling process provoked only transitory changes which returned to baseline values during kindling and immediately after. Analysis of pre- and post-stimulation periods demonstrated compensatory changes in W and PS percentage during the late stages of kindling. We conclude that rather than sleep diminution, kindling provokes a circadian shift of W and PS stages. PMID- 1743182 TI - A comparison of recurrent inhibition and of paired-pulse facilitation in hippocampal slices from normal and genetically epileptic mice. AB - Tottering mice exhibit inherited generalized epilepsy of the 'absence' type. In hippocampal slices from these mutant mice studied in vitro, pairing an alvear antidromic stimulus to an orthodromic one revealed a strong recurrent inhibition (RI) of CA1 pyramidal neurons. RI was maximal at 10 ms inter-pulse interval (IPI 70% decrease of population spike, PS) gradually decreasing to 15% at 320 ms IPI. At 10 ms IPI it shifted the input/output curves to the right and decreased maximum PS. In the group of slices from epileptic mice the early part of RI (2.5 60 ms) was indistinguishable from that of normal mice, with respect to both its strength and its liability to activity-dependent decrement induced by a train of antidromic stimuli (8 s, 5 Hz). However, the delayed part (80-320 ms) was slightly stronger in the epileptic group. Also in this group only the train of antidromic pulses caused a significant and lasting decrease in the unconditioned orthodromic PS. Paired-pulse facilitation was equally strong in the 2 groups of slices. It is concluded that mechanisms underlying epileptogenic hyperexcitability in the tottering mutant may not include a failure of inhibition, at least in the CA1 area of the hippocampus. On the contrary some inhibitory mechanisms may be stronger. PMID- 1743183 TI - Trans-2-en-valproate: reevaluation of its anticonvulsant efficacy in standardized seizure models in mice, rats and dogs. AB - The anticonvulsant potency of the trans isomer of 2-en-valproate (trans-2-en-VPA) was determined in standardized models for different seizure types in rodents and dogs. In mice and rats, adverse effects were quantified by the rotarod and chimney tests. Clinically established antiepileptic drugs (valproate, ethosuximide, phenobarbital, carbamazepine, phenytoin, diazepam) were used for comparison. Based on time course studies, drug potencies were determined and compared at the individual time of peak anticonvulsant effect. Potency comparisons were based on administered dosages and, in the case of trans-2-en-VPA and valproate, also on plasma levels determined after administration of anticonvulsant doses. The data show that trans-2-en-VPA exerts anticonvulsant effects against different seizure types, i.e., myoclonic, clonic, and tonic seizures in rodents and (myo)clonic seizures in dogs. In most seizure models, trans-2-en-VPA was more potent than valproate, when both compounds were compared at their individual times of peak effect. Time course and pharmacokinetic studies showed that duration of action and pharmacokinetic characteristics of trans-2-en VPA and valproate are similar. In the rotarod and chimney tests in mice and rats, trans-2-en-VPA was more potent than valproate. However, because of the higher anticonvulsant potency of trans-2-en-VPA, protective indices calculated from rodent models were similar to those of valproate. Similarly, in dogs trans-2-en VPA exerted anticonvulsant effects at doses below those which induced sedation and ataxia. In view of the previously reported advantages of trans-2-en-VPA compared to valproate with respect to teratogenic and hepatotoxic effects, the present data substantiate that trans-2-en-VPA might be a valuable alternative to valproate in antiepileptic therapy. PMID- 1743184 TI - Spike-wave discharges and sleep-wake states in rats with absence epilepsy. AB - The occurrence of spike-wave discharges was studied in relation to the daily fluctuations of vigilance level in rats. Eight rats of the WAG/Rij strain, an animal model for idiopathic generalized epilepsy of the absence type, which were equipped with cortical EEG and nuchal EMG electrodes, served as subjects. It was found that spike-wave discharges predominantly occur during light slow wave sleep and passive wakefulness. REM sleep, active wakefulness, and deep slow wave sleep are less susceptible to the occurrence of spike-wave discharges. Finally, spike wave discharges tend to prevail in transitional states. A crucial role for the degree of stability of the level of vigilance in the genesis of absence seizures is suggested. PMID- 1743185 TI - Seizure frequency, patient-perceived seizure severity and the psychosocial consequences of intractable epilepsy. AB - It is generally recognised that the assessment of treatment effects in epilepsy using seizure frequency as the only outcome measure may lack sensitivity. A patient-based seizure severity scale has been developed and initial results confirm its reliability and validity. As part of the further development of this scale it is important to explore the relationship between seizure severity, seizure frequency and the psychosocial consequences of intractable epilepsy. One hundred patients with medically refractory partial seizures completed a quality of life questionnaire including measures of physical (seizure severity and frequency), social and psychological well-being (anxiety, depression, self esteem, locus of control and happiness). Multivariate analysis demonstrated that individual psychological variables were best predicted by other psychological variables. However, when these were removed from analysis, seizure severity was the most significant predictor of self-esteem (P = 0.005), locus of control P = 0.039) and anxiety (P = 0.048). Seizure frequency did not contribute significantly to the variance of any of the psychological factors. These results highlight the importance of considering seizure severity when assessing treatment effects in epilepsy and provide further evidence for the construct validity of a novel patient-based seizure severity scale. PMID- 1743186 TI - Magnetic resonance of intracranial epidermoids. AB - The magnetic resonance images of seven patients with biopsy-proven epidermoids were evaluated. The epidermoids were hypointense on T1-weighted images. Intermediate density images revealed the tumors to be heterogeneous in signal intensity consisting of areas of hypo- and isointensity. Signal intensity on T2 weighted images was hyperintense and inhomogeneous in all but one case. CT performed in five patients demonstrated the tumors to be well-defined hypodense lesions without contrast enhancement. PMID- 1743187 TI - Paranasal sinuses in pediatric patients by MRI: normal development and preliminary findings in disease. AB - A two-part study using medium field strength magnetic resonance imaging (MRI) was designed to describe the normal paranasal sinus development and to provide preliminary criteria for clinical sinus disease. In part I of the study the paranasal sinuses were retrospectively evaluated in 80 infants and children aged 0-17 years undergoing brain MRI for indications both unrelated and related to sinus disease. We developed MRI criteria for independent grading of paranasal sinus development and 'anatomical' sinus disease, i.e., disease as seen by the radiologist. We quantified the variability in extent of sinus pneumatization (a measure of sinus development) in infants and young children. Part II of the study was a double-blind prospective study in 21 patients to correlate 'anatomical' disease with 'clinical' sinus disease. In this limited preliminary study, clinical sinus disease was only seen in the patients with moderate or severe anatomical disease (sensitivity 100%; specificity 100%). PMID- 1743188 TI - Radioisotopic detection of portal hemodynamic changes after liver surgery. PMID- 1743189 TI - Radiology of the AS 800 artificial urinary sphincter; normal appearances and complications. AB - Thirteen adult male patients who had an AS 800 artificial urinary sphincter inserted are reviewed. Five have had malfunction, and in four the causes were diagnosed radiologically. These included: fistula formation, leakage of hydraulic fluid, air in the system, and inadequate deflation of the cuff. Since the sphincter is filled with contrast medium, it is ideally suited to radiological assessment. PMID- 1743190 TI - Preliminary European intravenous clinical experience with a new, low osmolar, nonionic contrast medium: ioversol (Optiray). AB - The intravenous clinical trial program of ioversol (Optiray), a low osmolar, nonionic, monomeric contrast agent characterized by high hydrophilicity, is evaluated on the basis of results from the first clinical trials conducted in Europe as part of the development of the 300 and 350 mgI/ml formulations: 7 double-blind, comparative trials and 5 single trials were performed in a total of 743 patients, of whom 472 received ioversol and 271 a monomeric nonionic reference product. The diagnostic efficacy of ioversol was equivalent or superior to that of the reference products and tolerance was comparable to that of nonionic agents in terms of pain and heat sensations. No significant difference in adverse reactions was found and all the contrast agents studied were well tolerated by the patients. PMID- 1743191 TI - Effects of two low osmolality contrast media on red blood cell filterability and aggregation in vitro. AB - The in vitro effects of ionic ioxaglate and non-ionic iopamidol were compared. Filtration measurements were carried out on an hemorheometer; erythrocyte aggregation was evaluated by means of an erythrocyte aggregometer, and red blood cell morphology was observed with an optical microscope. Ioxaglate and iopamidol reduced erythrocyte filterability to the same extent; by contrast neither ionic nor non-ionic contrast media significantly modified aggregation or shape of red blood cells. The decrease of erythrocyte deformability observed in this study may cause clotting in catheters or syringes during angiographies investigations. PMID- 1743192 TI - CT diagnosis of isolated systemic supply to the lung: a congenital broncho pulmonary vascular malformation. PMID- 1743193 TI - Effects of optimization and image processing in digital chest radiography: an ROC study with an anthropomorphic phantom. AB - A digital system for chest radiography based on a large image intensifier was compared to a conventional film-screen system. The digital system was optimized with regard to spatial and contrast resolution and dose. The images were digitally processed for contrast and edge enhancement. A simulated pneumothorax and two simulated nodules were positioned over the lungs and the mediastinum of an anthropomorphic phantom. Observer performance was evaluated with ROC analysis. Five observers assessed the processed digital images and the conventional full size radiographs. The time spent viewing the full-size radiographs and the digital images was recorded. For the simulated pneumothorax, the results showed perfect performance for the full-size radiographs and detectability was high also for the processed digital images. No significant difference in the detectability of the simulated nodules was seen between the two imaging systems. The results for the digital images showed a significantly improved detectability for the nodules in the mediastinum as compared to a previous ROC study where no optimization and image processing was available. No significant difference in detectability was seen between the former and the present ROC study for small nodules in the lung. No difference was seen in the time spent assessing the conventional full-size radiographs and the digital images. The study indicates that processed digital images produced by a large image intensifier are equal in image quality to conventional full-size radiographs for low-contrast objects such as nodules. PMID- 1743194 TI - Digital chest radiography: should images be presented in negative or positive mode? AB - The observer performance for video monitor images presented in positive mode ('bones black') was compared to that of images presented in negative mode ('bones white') in a digital system for chest radiography based on a large image intensifier. In the first part of the study (I), the original, non-linear grey scale reversal performed in the computer of the digital image intensifier system (DS1000) was studied together with fixed and variable settings of light and contrast. In the second part of the study (II), true grey-scale reversal performed in a minicomputer (Micro VAX II) where the images were also processed with edge and contrast enhancement, was studied. The time spent viewing the images was also recorded. Before the second part of the study, the image intensifier system was optimized with regard to spatial and contrast resolution and dose settings. Simulated pathology was randomly positioned over the lungs and the mediastinum of an anthropomorphic phantom. Observer performance was evaluated with Receiver Operating Characteristic (ROC) analysis on the digital images. In the first part of the study, a significant advantage for the positive images was seen, but no significant difference between fixed and variable settings of light and contrast. In the second part of the study, no significant difference in the detectability of the test structures was seen between positive and negative images. A significant improvement in the detectability was seen between the first and the second part of the study for the nodules over the mediastinum in both negative and positive images. No significant difference in the time spent observing positive and negative images, was seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743195 TI - The scatter-to-primary ratio as a function of varying X-ray absorption measured by computed radiography. AB - Some scatter studies have previously been conducted using film as a detector. The serious limitations caused by the narrow latitude, the non-linear density response, and the required optical densitometric measurements of film can be avoided by computed radiography (CR) which provides linear numeric data over a wide dynamic range. The imaging plate is used as a large-area detector and the data is analyzed from the computer memory. Variation in the scatter-to-primary ratio within an image caused by absorption differences was simulated in a water aluminum phantom. The measurement technique showed repeatable results, being comparable to the values expected on the basis of previous studies. A multiple pencil-beam (MPB) imaging device was also compared to a standard 1:12 grid by this technique. The maximal scatter-to-primary ratio in our model was up to 7.9 with no scatter reduction, 1.5 with grid, and 0.4 with the MPB device. The variation caused by the absorption of primary radiation was much less in the MPB modality, and the MPB system was also less sensitive to an increase in the used tube voltage from 60 to 120 kVp. The benefits of multiple pencil-beam imaging in scatter reduction are briefly discussed. PMID- 1743196 TI - Transabdominal ultrasound of the stomach: a pictorial essay. PMID- 1743197 TI - Radiologic aspects of breast cancers detected through a breast cancer screening program. AB - Early detection of breast cancer and reduced mortality in women with this disease is today attributed to the widespread use of mammography. High-quality performance is essential in every step of breast cancer screening programs in order to avoid unnecessary anxiety and surgery in the women concerned. This report presents the radiologic aspects of screening cancers. A total of 8370 asymptomatic women aged between 50-69 years were screened with 2-view mammography, of which only 70 (0.84%) were selected for surgery after a thorough work-up. Cancers were verified histologically in 61 women and 9 showed non malignant histology, giving a cancer detection rate of 7.3 cancers per thousand screened asymptomatic woman. The benign/malignant ratio in the operated cases is thus approximately 1:7. The cancers detected showed all existing types of mammographic features where 77% (47 cases) showed rather typical findings, such as spiculated densities both with and without microcalcifications and with microcalcifications only. The remaining 23% (14 cases) showed parenchymal distortions, asymmetric and well-defined densities, both with and without calcifications. Our results indicate that surgery can be minimized without impairing the breast cancer detection rate. Radiologists in screening programs should be aware that a large proportion of non-palpable breast cancers present in rather unconventional forms. This point is important in order to maintain a high cancer detection rate and thereby justify the widespread use of mammography as a screening tool for breast cancer in asymptomatic women. PMID- 1743198 TI - Fibroadenoma of the breast: in vivo magnetic resonance characterization. PMID- 1743200 TI - 1992 and all that. PMID- 1743199 TI - Magnetic resonance findings in 92 acoustic neuromas. AB - A retrospective analysis of the MR findings in 92 cases of acoustic neuromas is presented. The method of examination included in all cases intravenous injection of Gadolinium (Gd-DTPA or DOTA) with realization of sections in the axial and coronal planes. In 21 cases native MR studies were performed in the axial plane, before Gadolinium injection, with T1WI (n = 21), and T2WI (n = 6) images. Tumors were strictly intracanalar in 19 cases (20.7%), only localized in the cerebellopontine angle (CPA) in 5 cases (5.4%), and in 68 cases (73.9%) the tumors had intra- and extracanalar components. In this last group of lesions, 63.2% completely filled the internal auditory canal (IAC), and 36.8% occupied the internal portion of the IAC. In most cases (85.3%) the mean diameter of the CPA component was less than or equal to 2.5 cm. Lesions were more frequently homogeneous (58.8%) after Gd i.v.-enhancement. Heterogeneity was noted mainly in large lesions (greater than 2.5 cm: 100%). In all cases but one, the tumors were round, or oval-shaped, well-delineated, and did not present significant contact with the petrous bone. In 80.9% of CPA lesions, the center of the tumor was posteriorly excentered in relation to the internal auditory canal, whereas it was centered in 16.2% of cases. Widening of the IAC was observed in 51.1% of cases. In 45.2% of tumors of the CPA, smoothing of the posterior edge of the porus was visible. PMID- 1743201 TI - An autoradiography study of postoperatively labelled thyroid tissue and iodine storage. AB - Samples of fresh thyroid tissue obtained from 15 patients undergoing thyroid surgery were incubated with iodine 125 in culture solution to which thyroid stimulating hormone (TSH) had been added and then examined by autoradiography. The radioactivity registered actively during the 90-min incubation period was primarily found in the lumina of follicles. Even morphologically similar follicles showed very heterogeneous uptake of radioiodine; small follicles often contained the highest concentrations of activity. The method applied appears to be particularly useful for answering the question as to whether and to what extent individual papillary or follicular thyroid carcinomas are able to store radioiodine. This information obtained immediately after surgery may contribute towards establishing the patient's prognosis and help in deciding on postoperative therapy and follow-up. Because of the heterogeneity of radioiodine uptake, it is mandatory to examine a representative sample of carcinoma tissue in order to obtain well-established results. PMID- 1743202 TI - Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung. AB - Iodine 123 N-isopropyl-p-iodoamphetamine (123I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied 123I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of 123I-IMP into the medial cubital vein, the time activity curve for 60 min and the regional activity using 1 frame per minute and a 64 x 64 matrix were obtained. The 123I-IMP clearance curve was described as follows: C(t) = A1e-k1t + A2e-k2t (A1, A2: intercepts, and k1, k2: slopes of the exponential components). 123I-IMP clearance was delayed in smokers, and k2 was smaller in smokers. Also, a correlation between k1, k2, and the number of cigarettes smoked per day was found (r = -0.65, r = -0.74, respectively, P less than 0.01). In conclusion, this study suggests that the delayed clearance and retention of 123I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking. PMID- 1743203 TI - Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies. AB - To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by less than or equal to 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines. PMID- 1743204 TI - Monoclonal antibody BW431/26 labelled with technetium 99m and indium 111: an investigation of the biodistribution and the dosimetry in patients. AB - As a competitive diagnostic tool for the detection of malignant tumours and other pathological conditions, monoclonal antibodies have long been established. Herein we give the biokinetic data of the antibody BW 431/26 and the consequent radiation dose to patients. These parameters were recorded in 39 patients, using the antibody labelled either with technetium 99m or indium 111. Remarkable differences were observed between the two radionuclides. Whereas the indium labelled one showed biexponential elimination kinetics, the technetium-labelled one is eliminated linearly over time. The distribution pattern of the two is identical, although the radiation dose varies quite a lot, being 20-fold higher with indium 111 when total body exposure is taken into account (for 111In the whole-body radiation exposure is 0.1 mGy/MBq; for 99mTc it is 0.0047 mGy/MBq). With respect to these results and considering the general availability of the technetium-labelled Ab, it is the best choice for diagnostic use. PMID- 1743205 TI - Clinical experience with the adrenal scanning agents iodine 131-19 iodocholesterol and selenium 75-6-selenomethylcholesterol. AB - Adrenocortical scintigraphy with iodine 131-19-iodocholesterol or selenium 75-6 selenomethylcholesterol was performed in 94 patients with proven or suspected adrenal disease. According to the final diagnosis, 36 patients suffered from primary aldosteronism, 33 from Cushing's syndrome, 8 from low renin hypertension, 6 from nonfunctioning adrenal tumour, 4 from simple obesity, 3 from adrenal metastases, 1 from congenital adrenal hyperplasia, 1 from virilizing adrenal adenoma, 1 from extraadrenal phaeochromocytoma, 1 from ganglioneuroma. Surgical confirmation of the diagnosis was obtained in most cases. With a few exceptions, the scintigraphy results were consistent with the final diagnosis. The two tracers were equally effective adrenal scanning agents. Tracer concentration was measured in a number of surgical specimens, mostly from patients given selenocholesterol. This measurement in surgical samples has not been reported in previous studies with this agent. The results provided a direct validation of uptake measurements in vivo. The data, collected over a 17-year period, demonstrate that despite the advent of new imaging techniques, adrenal scintigraphy that gives both functional and morphologic information still has an important role in the diagnosis of adrenal disease. PMID- 1743206 TI - Excretion of gallium 67 in human breast milk and its inadvertent ingestion by a 9 month-old child. AB - The concentration of radioactivity excreted in breast milk following the administration of gallium 67 to 3 patients was measured in milk samples obtained for several days after injection. Similar values were obtained from all 3 patients, with milk samples obtained approximately 120 h after administration containing 4.3-5.7 Bq/ml per MBq of 67Ga administered. These values are lower than those previously reported. The image of a child who had inadvertently been breast-fed for 48 h after administration of 67Ga to the mother showed activity in the intestines only. Our results seem to confirm recommendations by other authors that gallium scintigraphy should be avoided in nursing mothers. Should the administration of 67Ga be inevitable, breastfeeding should be discontinued, since interruption periods of approximately 2 weeks may be required to reduce the effective dose equivalent to the infant below 1 mSv. However, close contact between mother and child need not be avoided. PMID- 1743207 TI - Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization. AB - The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using [U-11C]-D-glucose as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62 +/- 19 (mean +/- SEM) mumol hg-1 min-1, and the half saturation constant was found to be 4.1 +/- 2.3 mM. PMID- 1743209 TI - Unexpected uptake of technetium 99m hexakis-2-methoxy-isobutylisonitrile in giant lymph node hyperplasia of the mediastinum (Castleman's disease). AB - The case of a patient with giant lymph node hyperplasia of the mediastinum who unexpectedly showed focal uptake of technetium 99m hexakis-2 methoxyisobutylisonitrile (99mTc-MIBI) is presented in this article. The patient was included in our research programme of tumor imaging with 99mTc-MIBI because the appearance of the mass on the chest radiogram and CT scan resembled a mediastinal tumour. Final diagnosis of giant lymph node hyperplasia was achieved through histopathological examination of the surgically removed lymph node. PMID- 1743208 TI - Scintigraphy in the clinical evaluation of disorders of mineral and skeletal metabolism in renal failure. AB - In patients with renal bone disease skeletal and extra-skeletal abnormalities can be visualised using conventional bone scintigraphy. Some of these abnormalities are associated with characteristic scintigraphic appearances, which are reviewed in detail, and the possible mechanisms involved are discussed. Specific imaging with iodine 123 serum amyloid P component and iodine 131 beta 2-microglobulin is also discussed in the diagnosis of beta 2-microglobulin amyloidosis specific to patients on dialysis. In the light of available evidence, it appears that bone scintigraphy plays, so far, a limited role in the clinical evaluation of skeletal and extra-skeletal abnormalities in chronic renal failure. The potential role of bone scintigraphy in identifying patients with aluminium-related bone disease needs to be investigated further, and in this respect special attention must be given to the problem of high soft-tissue activity associated with impaired renal function. Timing haemodialysis sessions before scintigraphic imaging deserves wider recognition as it reduces high soft-tissue activity, thereby allowing bone uptake to be assessed more accurately. Specific imaging of amyloidosis resulting from beta 2-microglobulin deposition is a promising technique, but the relative value of the two proposed radiopharmaceuticals needs further clarification. PMID- 1743210 TI - A simple method for the preparation of gallium chloride from the citrate solution. PMID- 1743211 TI - Small-intestinal abnormalities in cystic fibrosis patients. AB - A survey is given of the pathophysiology of the main alterations in the small intestine of cystic fibrosis patients. Special attention is paid to the understanding of meconium ileus in the fetus and the newborn, the repercussion of duodenal acidity on the duodenal mucosa and the intraduodenal digestion, and primary and secondary biochemical alterations in the secretory-digestive absorptive function of the small-intestinal mucosa. The meconium equivalent syndrome and its connection with the atypical course of intussusception and appendiceal perforation with silent pelvic abscess are also discussed. PMID- 1743212 TI - Left ventricular thrombus in a 2-year-old boy with cardiomyopathy: lysis with recombinant tissue-type plasminogen activator. AB - A 2-year-old boy with cardiomyopathy and clinical signs of cardiac failure presented with an echodense structure in the left ventricle. This structure was seen from different echocardiographic views adjacent to a hypokinetic area of the apex and lateral free wall. It was different in texture and motion from the underlying myocardium and thus met the diagnostic criteria of a left ventricular thrombus. This thrombus protruded into the cavum and was partly mobile. In view of a high embolic risk, thrombolytic therapy with recombinant tissue plasminogen activator was started. The thrombus resolved within 72 h without any embolic or bleeding complications. No recurrence of the thrombus was observed during a 3 month follow up period. PMID- 1743213 TI - Documented latent coeliac disease in a child with insulin-dependent diabetes mellitus. AB - The histological development of coeliac disease has been documented in a child with insulin-dependent diabetes mellitus (IDDM). Serum antigliadin IgG was temporarily present at the onset of IDDM. It is assumed that IDDM may exert a trigger effect on the development of coeliac disease. PMID- 1743214 TI - Optic gliomas in children with neurofibromatosis type 1. AB - Over a 24-year period, optic gliomas were found in 29 children, 16 of whom had neurofibromatosis type 1 (NF-1). These 16 children comprised 21% of all children referred for management of NF-1 and its complications. The finding of optic glioma led to the diagnosis of NF-1 in 4 children. The mean age at diagnosis of optic glioma in NF-1 children was 6.4 years, and the average estimated duration of visual symptoms prior to diagnosis was 2.1 years. Most optic gliomas in NF-1 children were ascertained because of a visual complaint (69%), and an even greater number of children (88%) had an abnormal ophthalmological examination. The optic chiasm was involved in 75% of the patients. All of the seven children with optic glioma examined by visual evoked potential had an abnormal response ipsilateral to the tumour. The majority of the children received radiation therapy. After a mean follow up period of 5.8 years no deaths had occurred due to optic glioma, but in 35% of the children vision was worse. We conclude that optic glioma is a common, serious complication in NF-1 children. Routine care of such patients should include regular noninvasive investigations aimed at detecting lesions of the optic pathway. PMID- 1743215 TI - Cytoplasmic granules in leukaemic cells of the cerebrospinal fluid in a child with non-granular acute lymphocytic leukaemia. AB - We report a child with relapsed acute lymphocytic leukaemia in whom cytoplasmic granules were present in the leukaemic cells of the cerebrospinal fluid (CSF) but not in those of the bone marrow (BM). The leukaemic cells of the BM were of B cell lineage whereas those of the CSF had both B-cell and myeloid antigens. PMID- 1743216 TI - Transcobalamin II deficiency: case report and review of the literature. AB - A male Caucasian infant presented at 6 weeks of age with failure to thrive, diarrhoea, macrocytic anaemia, and decreased IgG. He had normal serum B12 and folate levels. Serum cobalamin binding capacity showed no detectable transcobalamin II. Both parents showed levels consistent with a heterozygous state. The literature is extensively reviewed, and the importance of early diagnosis to prevent neurological dysfunction is stressed. PMID- 1743217 TI - Cord serum IgE and early detection of the atopic phenotype: suitable for routine screening? AB - Cord serum IgE has been shown to be a valuable marker for the prediction of atopy. Our study was designed to verify these findings for possible systematic screening recommendation. Our study consisted of 338 children who were followed from birth to 18 months. Cord serum IgE was measured by paper immunosorbent test and radioimmunoassay. All other data (sex, family history and environment, diet, occurrence of atopic manifestations) were recorded. Of the 338 children, 118 (34.9%) developed obvious clinical symptoms of atopy during the study period. Using the receiver operator curve we found an IgE level of 1.20 IU/ml to be the best cut-off point as a predictor of atopy with 95% specificity but 13% sensitivity. Combination with other predictors such as sex, family history, environmental factors and diet did not increase the predictive value of the test. Because of this low sensitivity we conclude that cord serum IgE is insufficient to detect individuals at risk for atopy even if associated with genetic and environmental factors. Thus it should not be recommended for routine screening purposes; more sensitive markers are needed. PMID- 1743218 TI - Cartilage hair hypoplasia in infancy: a misleading chondrodysplasia. AB - Among children with recessive metaphyseal dysplasia, cartilage hair hypoplasia, as described by McKusick is often recognized only during the 2nd year or later. The early radiological changes observed in six children with cartilage hair hypoplasia demonstrate the misleading aspect of this chondrodysplasia: micromelia, massive appearance of the long bones and round inferior femoral epiphyses, without distinct metaphyseal involvement. Early diagnosis permits the organisation of clinical, immunological and orthopaedic follow up and allows for correct genetic counselling. PMID- 1743219 TI - Chronic pancreatitis in a child with glycogen storage disease type 1. AB - A case of chronic pancreatitis in an 8-year-old boy with glycogen storage disease type 1a (GSD 1a) is presented. This patient had a history of hyperlipidaemia unresponsive to dietary therapy, e.g., a carbohydrate-rich diet, uncooked cornstarch, and nocturnal intragastric tube feedings. He had recently suffered bouts of abdominal pain and diarrhoea. Serum amylase and trypsin were elevated, abdominal CT revealed the presence of a pseudocyst of the pancreas. The presence of chronic pancreatitis was confirmed by endoscopic retrograde cholangiopancreatography and an infected pseudocyst was removed at laparotomy. PMID- 1743220 TI - Mitral valve and tricuspidal valve prolapse in Melnick-Needles syndrome. PMID- 1743221 TI - An infant having Potter facies without pulmonary hypoplasia after prolonged oligohydramnios due to a placental mass. PMID- 1743222 TI - Acute caffeine poisoning in a child. PMID- 1743223 TI - pT1 bladder cancer. AB - pT1 bladder tumors invade the lamina propria and are more aggressive biologically than superficial pTa or in situ carcinomas (Tis). Among patients with pT1 tumors treated by transurethral resection (TUR), 30% develop a muscle-invasive neoplasm within 3-5 years, but intravesical chemotherapy or BCG reduce progression rates to 20 and 14%, respectively. Tumor variables favoring progression include multiple, recurrent pT1 tumors, high grade (G3), solid configuration and associated Tis. Many pT1 tumors can be managed conservatively, but patients failing an adequate trial (3-6 months) of TUR and intravesical therapy are best treated by cystectomy. PMID- 1743224 TI - Analyses of factors affecting the outcome of combination chemotherapy in patients with advanced bladder cancer. AB - Thirty-seven patients with advanced bladder carcinoma were treated with a combination of methotrexate, vinblastine, adriamycin and cisplatin (M-VAC). Attempts were made to identify the factors related to the results of the present regimen using multivariate analyses. Factors related to the results were presence of distant metastases and prior chemotherapy. The effect of the M-VAC chemotherapy was disappointing in most patients with distant metastases and prior chemotherapy. This was prominent in patients with prior chemotherapy including cisplatin. These results seem to show clinically the development of resistance to cisplatin in advanced bladder cancer. Methods to overcome this resistance should be studied. PMID- 1743225 TI - Alpha-interferon and oral fluorouracil in the treatment of unremovable and/or metastatic renal cancer. AB - We present the results obtained in a study of the pharmacological action (phase II) of alpha-interferon and oral fluorouracyl administered in our 2-year study (Feb. 1988-Feb. 1990) in 10 patients suffering from surgically unremovable or metastatic renal cancer. Our results were: 1 patient with complete regression of lung metastasis; 5 with progressive disease within 3-4 months from beginning of treatment and 2 deaths with stable disease after 4-5 months. Two patients abandoned treatment and their disease progressed within 4-5 months. PMID- 1743226 TI - Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette Guerin) in superficial bladder cancer. AB - Both intravesical mitomycin C (MMC) and bacillus Calmette-Guerin (BCG; Pasteur strain F) were effective in the present prospective randomized multicenter study consisting of 91 patients with frequently recurrent superficial (Ta-T1) bladder cancer. The result was in favour of BCG, as shown by the measurements with complete response (CR), disease-free interval and recurrence rate. CR of 58% with MMC and 40% with BCG were reached in 22 instillation series on carcinoma in situ of 18 patients. Due to side effects, MMC instillations were discontinued in 8.6%, and BCG instillations in 19.6%, respectively. After the 2-year follow-up also 1 case of pulmonary tuberculosis occurred in the BCG group. PMID- 1743227 TI - Vesicoureteral reflux in the renal transplantation candidate. AB - The incidence and severity of urinary tract infection episodes were evaluated in two groups of renal transplantation patients. Group 1 consisted of 11 patients transplanted following successful surgical correction of a noninfected vesicoureteral reflux in native kidneys, and group 2 of 28 patients transplanted with a noninfected vesicoureteral reflux. An increased incidence of acute urinary tract infection episodes was noted in group 2 as compared to group 1 (42.8 vs. 18%), with a mean of 2.6 +/- 1.4 episodes per patient in group 2 and 0.5 +/- 0.32 in group 1. Asymptomatic bacteriuria was not statistically different in the two groups (36.4 vs. 25%). In group 2, the incidence of urinary tract infection episodes increased in patients presenting high-grade (3 and 4) reflux in native kidneys. Despite the relatively low number of patients involved, our observations indicate that high-grade vesicoureteral reflux in native kidneys must be operated before transplantation, even when there is no history of urinary tract infections and urine cultures are sterile. PMID- 1743228 TI - Ureteroneocystostomy in the neuropathic bladder associated with high-grade reflux. AB - Between 1976 and 1987, a total of 25 ureteroneocystostomies were performed in 17 patients with neuropathic bladder associated with high-grade reflux III-V. An overall success rate of 82.4% is reported. Special complications included postoperative renal deterioration, especially after tapering of megaureters. During follow-up, contralateral reflux was noticed in 44% after unilateral treatment of reflux. Preoperative cystoscopy to define trigone abnormalities is mandatory. PMID- 1743229 TI - Flow-cytometric analysis of testes in infertile men: a comparison of the ploidy to routine histopathologic study. AB - DNA flow-cytometric analysis was performed on the testicular needle biopsies of 25 infertile men with azoospermia or oligozoospermia to evaluate the ability of DNA histograms in order to detect and quantify alterations in spermatogenesis. Concomitant histopathologic study was performed on the tissues from needle biopsy. In contrast to difficulty in quantifying spermatogenesis in histopathologic examination, flow-cytometric analysis revealed characteristic ploidy patterns in the relative proportions of haploid (1 n), diploid (2 n) and tetraploid (4 n) cells corresponding to the histopathologic appearances of normal spermatogenesis, hypospermatogenesis, maturation arrest and aspermatogenesis. Findings evaluated with flow cytometry were well correlated with those from routine histopathologic study. In 21 of these patients (84%) there was concordance between histopathologic and flow-cytometric diagnoses. However, in 4 patients (16%) there was discordance between two diagnostic modalities. In conclusion, DNA flow cytometry of testicular biopsies was a reproducible, objective and quantitative approach in evaluating infertile men, and it is a promising method to investigate spermatogenesis in an outpatient clinic in lieu of formal testicular histopathologic study. PMID- 1743230 TI - Hypospadias: Duckett pedicle tube urethroplasty. AB - The Duckett transverse tube pedicle urethroplasty was used to repair the primary hypospadias of 190 boys over an 11-year period. The fistula rate was 34.4%. The majority of boys have obtained a satisfactory cosmetic and functional result with a single operation. PMID- 1743231 TI - Renal duplications: the impact of perinatal ultrasound on diagnosis and management. AB - Perinatal urology is a rapidly expanding field in pediatric urology bringing significant changes in the diagnosis and management of congenital uropathies. Renal duplication was detected by antenatal and perinatal ultrasound in 19 cases (22 duplicated systems). In most cases, no precise diagnosis could be established in utero (4 of 13), but this lack of accuracy is of little clinical significance since all newborns with suspected uropathies undergo complete urological investigations in the perinatal period. Voiding cystogram demonstrated reflux in 11 of 22 cases. On postnatal urography a functioning upper pole was demonstrated in 11 of 22 kidneys. There were 12 ureteroceles: in 8 a nonfunctioning upper pole was removed, while 3 were endoscopically incised with good functional improvement and 1 was reimplanted. Early recognition of congenital uropathies in association with duplication by prenatal ultrasound significantly improves patient care allowing early postnatal relief of obstruction by less invasive methods and before infection or persistent obstruction worsens the prognosis. PMID- 1743232 TI - An operation for incisional lumbar hernia. AB - To date, no standard technique for incisional lumbar hernia repair can be recommended since it depends on the size of the defect in the transversalis fascia. A new technique for this purpose, by using plication of the normal fascia, is described. PMID- 1743233 TI - Quantitative evaluation of the penile vascular status by means of the 99mTc penogram in conjunction with either papaverine or prostaglandin E1 in the anaesthetised baboon model. AB - The evaluation of both the arterial blood supply and the venous drainage of the penis is essential in the assessment of the impotent male. The vasoactive drugs papaverine and prostaglandin E1, as intracavernous injections, cause penile erections by influencing arterial blood supply and venous drainage. These drugs were used in a baboon model together with a 99mTc-penogram to provide information on the vascular status of the penis. An increase in penile blood pool was observed, more dramatic and rapid after administration of papaverine. A quantitative assessment of the vascular status seems possible and will next be monitored in a vascular-compromised baboon for purposes of clinical application. PMID- 1743234 TI - DNA ploidy, S phase fraction and G2 fraction as prognostic determinants in prostatic adenocarcinoma. AB - The results of DNA flow cytometry (FCM), histological features and clinical stage of prostatic adenocarcinoma were correlated to outcome in 91 patients during a mean follow-up period of 15.6 years. Aneuploidy was detected in 33 (36%) tumours, and 59 (64%) tumours were diploid. Eighteen (20%) tumours showed a tetraploid DNA index. The frequency of tetraploidy increased towards high-stage and high-grade tumours. Aneuploidy, high S phase fraction (SPF) and G2 fraction were significantly related to clinical stage, histological grade and perineural infiltration. Progressing tumours (T category) had higher SPF values (p = 0.0248), and progression in N (p = 0.0122) and M categories (p = 0.0021) was related to high G2 fraction as well. In T1-2 tumours, DNA ploidy (p = 0.0280) and SPF (p = 0.0230) predicted progression, whereas histological grade had no significant predictive value. The clinical stage (T) predicted crude survival (p = 0.0005). Results show that FCM gives prognostic information in prostatic adenocarcinoma beyond that of histological grading. PMID- 1743235 TI - Nomogram for penile biothesiometry. AB - Three hundred and fifty men, aged between 17 and 80 years, with normal sexual anamnesis and without any neurological pathology, underwent finger (index) and penile biothesiometry using a biothesiometer. Tabular and graphical nomograms were obtained according to age and instrumental values. The use of the above mentioned nomograms is an effective aid in detecting each individual case. PMID- 1743236 TI - Urethral sphincteric responses to sacral root stimulation. AB - Deafferentation and stimulation of sacral nerves in patients with complete spinal cord lesions is a good model to study the parasympathetic influence on urethral behavior. During intradural sacral deafferentation from S2 to S4/S5 in preparation for implantation of the Finetech-Brindley anterior sacral root stimulator, sacral roots were stimulated with 3 and 30 Hz and 3 and 10 V and the bladder and urethral responses noted. Stimulation of the posterior roots at 3 Hz gives a urethral relaxation without bladder contraction. At this frequency, anterior sacral root stimulation has no effect on bladder nor urethral pressure. Stimulation of the anterior roots at 30 Hz produces simultaneous bladder contraction and urethral relaxation. These findings support the presence of an afferent parasympathetic inhibitory mechanism in the spinal micturition center in the human. PMID- 1743237 TI - Bilateral renal cell carcinoma with caval invasion in a woman with duplicated inferior vena cava. AB - Workup of a woman presenting with a palpable right flank mass, detected bilateral renal solid lesions, later proved to be renal cell carcinomas, and caval invasion in the presence of duplicated inferior vena cava. This association does not appear to have been previously described. The patient underwent right radical nephrectomy, cavotomy and auriculotomy with caval thrombus removal and delayed enucleation of left renal masses and left adrenalectomy. Eighteen months after surgery the patient is alive and without local and distant recurrence. PMID- 1743238 TI - Cysts of the prostate, seminal vesicles and diverticulum of the ejaculatory ducts. AB - The close proximity of the prostate, vas deferens, seminal vesicles and ejaculatory ducts are a diagnostic challenge to the cysts located in that region. Three patients with diverticulum of the ejaculatory ducts, 2 with prostate cysts and 1 patient with seminal vesicle cyst are presented. Transrectal ultrasound, computed tomography and magnetic resonance imaging together with aspiration of the cyst establish diagnosis and probably prevent unnecessary exploration. PMID- 1743239 TI - Prostate cancer in a 75-year-old man after four decades of testicular androgen deprivation. AB - In a 75-year-old patient referred for mild obstructive symptoms, physical examination revealed a clinically manifest T2B cancer of the prostate (CaP) involving the right lobe, and bilateral testicular atrophy (TA), right cryptorchidism with TA after orchiopexy at age 10, and left mumps orchitis with secondary atrophy at age 35). Since the age of 35, the patient had a limited sexual life and fathered no children. Transrectal ultrasonography demonstrated a small prostate (21 cm3) with a large hypoechoic zone in the right lobe, an isoechoic left lobe and no sign of capsular/seminal involvement. Three biopsies of the right lobe demonstrated a cancer (Gleason 4-3; score 7) of the right lobe, 3 biopsies of the left lobe showed an atrophic prostate with slight intra-acinar hyperplasia and moderate dysplasia. Morphometric studies showed these findings to be consistent with long-standing androgen deprivation. Serum prostate-specific antigen (PSA) was 8.7 ng/ml, whereas serum testicular androgens were within the castrate value (serum testosterone 0.2 ng/ml, dihydrotestosterone less than 0.05 ng/ml). Serum LH and adrenal androgens were within normal ranges. Bone scan was negative and NMR demonstrated no nodal enlargement. Considering the age of the patient, antiandrogen therapy was given (cyproterone acetate 50 mg t.i.d.). The patient reported marked improvement at 3 and 6 months of follow-up and PSA fell to 1 ng/ml at month 6. However, repeat rectal exams and ultrasonography showed no dramatic modification of the gland. The patient has since been lost to follow-up. Two conclusions may be drawn from this observation. Testicular androgen deprivation at age 35 although leading to prostatic atrophy does not prevent the development of CaP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743240 TI - Urological complications associated to uterus didelphys with unilateral hematocolpos. A case report and review of the literature. AB - Complete duplication of vagina, cervix and uterus, with imperforate hemivagina and renal agenesis is a rare condition with less than 120 cases published. In those articles, urological complications are uncommon with only a 10% of the total. We report 2 cases of uterus didelphys with unilateral hematocolpos and ipsilateral renal agenesis with urological clinical complications. One of them presented a very rare onset complaining of acute urinary retention. The other patient was referred for difficulty in micturition and abdominal pain which is the most common symptom of this entity. A description of both cases and a literature review of this congenital complex syndrome and its urological complications are reported. PMID- 1743241 TI - Effect of lacidipine, a long-acting calcium antagonist, on hypertension and lipids: a 1 year follow-up. AB - The effect of lacidipine, a dihydropyridine calcium antagonist on lipid metabolism, has been followed in 8 patients with uncomplicated mild to moderate essential hypertension treated for up to 14 months. There were significant reductions in the systolic and diastolic pressures, from 167/102 to 146/91 mm Hg at 2 months, and to 137/85 mm Hg at the end of the study. Blood lipid concentrations did not change during the observation period (cholesterol 5.1 vs 5.3 mmol.l-1, triglycerides 1.1 vs 1.0 mmol.l-1, HDL-cholesterol 1.1 vs 1.2 mmol.l-1). The results show that lacidipine did not affect lipid metabolism and suggest that calcium antagonists may be safely prescribed for a prolonged period to patients with combined hypertension and hyperlipidaemia. PMID- 1743242 TI - Haemodynamic effects of glyceryl trinitrate following repeated application of a transdermal delivery system with a phasic release profile. AB - The haemodynamic effects and plasma concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites were investigated in 8 healthy male volunteers during 5 days of application of a new transdermal delivery system (TDS) with time dependent release characteristics, which were considered to prevent or to diminish development of nitrate tolerance. On the first and fifth day of administration the following haemodynamic parameters were determined: digital pulse ratio of height of systolic peak to height of dicrotic wave (i.e. a/b ratio), heart rate and systolic blood pressure under orthostatic conditions. Peak plasma concentrations of GTN were 139 and 155 pg.ml-1 on the first and fifth day of treatment, and the corresponding trough concentrations (i.e. 24 h after administration) were 52.5 and 36.6 pg.ml-1, respectively. Compared to placebo, the area under the effect curve of the a/b-ratio of the digital pulse was increased on the first (25.6%) and fifth day (13%). A significant increase of heart rate and a decrease of systolic blood pressure were seen only on the first day of treatment. The haemodynamic effects of sublingual GTN 0.8 mg were reduced by 69% (a/b-ratio) and 52% (standing heart rate) on the fifth day compared to the pretreatment values. Thus, the phasic release of GTN from the new TDS can be demonstrated by the time course of the plasma concentrations of GTN and its metabolites. Nevertheless, following repeated administration the hemodynamic effects are blunted. PMID- 1743243 TI - The effect of angiotensin II on haemodynamic and plasma noradrenaline responses to tyramine infusion in man. AB - Six normal volunteers were studied on four separate occasions. On each occasion they received two concomitant infusions which were either placebo/placebo, placebo/tyramine, angiotensin II/placebo or angiotensin II/tyramine. Angiotensin II infusion was given at a constant rate of 2ng/kg/min whereas the tyramine infusion consisted of 10 min increments at 1.25, 2.5, 3.75, 5, 7.5 and 10 micrograms.kg-1.min-1. Tyramine infusion caused a dose dependent increase in systolic blood pressure with increases in diastolic blood pressure and plasma noradrenaline only at the highest doses. These changes were not affected by concomitant angiotensin infusion. We have therefore found no evidence to support the enhancement of haemodynamic or plasma noradrenaline responses to tyramine infusion by low dose infusion of angiotensin II in man. PMID- 1743244 TI - Reproducibility of Doppler blood flow velocity waveform measurements: study on variability within and between day and during haemodynamic intervention in normal subjects. AB - Reproducibility of Doppler blood velocity waveform measurements in external and internal carotid, middle cerebral, and brachial arteries and ascending aorta was determined in 8 normal male volunteers twice daily on three occasions each separated by two or more weeks. Measurements were made in supine and standing positions at rest and after taking glyceryl trinitrate and in the supine position after performing a standardized exercise test. The Doppler blood flow waveform indices showed a between days coefficient of variation of less than 15% both for baseline measurements and during haemodynamic change induced by exercise or glyceryl trinitrate. We conclude that Doppler blood velocity waveform measurement in different vascular beds is reproducible at baseline and when the cardiovascular system is interrupted pharmacologically or physiologically. PMID- 1743245 TI - Treatment of insomnia with two benzodiazepines: a double-blind crossover study. AB - Twenty-eight patients (12 M, 16 F) with insomnia were treated with nitrazepam 5 mg/d and oxazepam 25 mg/d, each for 11 days, in a double-blind crossover comparison with placebo. Half the patients received nitrazepam in the first drug period, and oxazepam in the second and the other half followed the contrary sequence. Both nitrazepam and oxazepam were found to be effective in inducing sleep and increasing sleep quality. No effects on dreaming or adverse effects were found. Nitrazepam did influence the frequency of awakening, but only in the second drug period. In the first period it reduced self-waking. It is concluded that both nitrazepam and oxazepam were effective in inducing sleep and in improving sleep quality. PMID- 1743246 TI - Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers. AB - RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and ex-vivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg.l-1. There were no clinical or biological adverse reactions to RP 48740 during the study. PMID- 1743247 TI - Enhancement of propoxyphene bioavailability by ethanol. Relation to psychomotor and cognitive function in healthy volunteers. AB - The interaction between a single oral dose of 130 mg propoxyphene and 0.5 g/kg body weight ethanol was investigated in 12 healthy male volunteers by 9 objective performance tests, 8 visual analogue self-rating scales and the measurement of plasma propoxyphene, norpropoxyphene and ethanol concentrations, using a double blind threeway crossover design. Volunteers were each given one of three treatments, propoxyphene + ethanol, placebo + ethanol and propoxyphene alone, separated by a two week interval. The performance tests were completed before and 1.25 and 4 h after drug intake, and the self-rating scales before and 1.25, 4 and 10 h after it. Ethanol was shown to enhance the bioavailability of propoxyphene by 25% probably by reducing its first-pass metabolism. However, despite this pharmacokinetic effect no pharmacodynamic interaction was found. Subjective ratings disclosed that the effect of ethanol on physical and mental sedation predominated over the effects of propoxyphene. PMID- 1743248 TI - Urinary glucuronide excretion of fenofibric and clofibric acid glucuronides in man. Is it polymorphic? AB - The possible polymorphism of the glucuronidation reaction in man has been investigated using two hypolipidaemic compounds, fenofibrate and clofibrate, as the test probes. The formation of fenofibryl and clofibryl glucuronides was identified by their susceptibility to hydrolyses by beta-glucuronidase. The urinary excretion of the glucuronides was measured in 72 healthy volunteers after a single dose of fenofibrate, and in 104 subjects given a single dose of clofibric acid. Fenofibrate was excreted at a lower rate than clofibrate, since 13.94% and 26.55% of the doses of fenofibrate and clofibrate respectively, were recovered in urine in 8 h. Correlation analysis indicated that sex and body mass index significantly influenced the formation of fenofibryl glucuronide, whereas age and oral contraceptives affected the excretion of clofibryl acid glucuronide. The 8-hour urinary excretion patterns of clofibryl glucuronide and of clofibric acid presented a Gaussian distribution, whereas those of fenofibryl glucuronide and fenofibric acid showed 2 populations. When the metabolic ratio free fenofibric acid/glucuronide was considered, 84.7% of subjects presented the ratio 0.147, and 15.3% had the 3-fold higher ratio of 0.421. The study has shown, in the human population studied, that the glucuronidation of fenofibric acid but not that of clofibric acid may present a polymorphism. PMID- 1743249 TI - Pharmacokinetics of halofantrine and n-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine. AB - Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax) = 896 and 491 ng.ml-1; time to reach the Cmax (tmax) = 15 and 56 h; elimination half-life (t1/2) = 91 and 79 h and the mean residence time (MRT) = 71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients. PMID- 1743250 TI - Dose-dependent absorption and elimination of cefadroxil in man. AB - The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg.kg-1. As the dose of cefadroxil increased from 5 to 15 and 30 mg.kg-1, the peak plasma concentrations, normalized to 5 mg.kg-1, decreased significantly from 15.1 to 10.7 and 7.6 mg.l-1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min.mg.l-1. When the same subjects were given 5 mg.kg-1 of cefadroxil together with 45 mg.kg-1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose of cefadroxil. Although the absorption rate decreased as the dose increased, the systemic availability of cefadroxil was essentially complete at all doses, as judged by the 24 h urinary recoveries of the antibiotic. Kinetic analysis of the plasma concentration-time curves gave the best fit with a zero-order followed by a first order absorption process, consistent with saturable intestinal absorption of cefadroxil. The elimination rate of cefadroxil was directly related to dose and plasma concentrations, and the clearance at the dose of 5 mg.kg-1 was significantly increased by the simultaneous administration of high-dose cephalexin. The renal clearance of cefadroxil ranged from 98 ml.min.l-1 at total plasma cephalosporin (cefadroxil + cephalexin) concentrations less than 2.5 mg.l 1 to 156 mg.l-1 at concentrations greater than 40 mg.l-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743251 TI - Antibiotics policies in the developing world. PMID- 1743252 TI - Racemic therapeutics--ethical and regulatory aspects. AB - Racemic therapeutics are fixed ratio mixtures of stereoisomers to be regarded biologically as different compounds. Usually only one of the isomers fully contributes to the therapeutics action, and the other is often classifiable as "isomeric ballast". Due to differences in turnover and pharmacokinetics, the proportion of enantiomers (1:1 in the racemate) continuously changes in plasma. The implications of the neglect of stereoselectivity for various levels in the investigation of racemic drugs are discussed and summarized in Table 2. The fact is that clinical investigators, Ethical Committees and regulatory authorities have for decades accepted invalid pharmacokinetic data on some 25% of therapeutics. That those racemates remain in use make the benefit of and necessity for kinetics generally questionable. Exposure of patients to the "isomeric ballast" present in about 50% of the most commonly used drugs will probably contain for many decades. As a result of a change in attitude of the regulatory authorities, however, for new drugs the choice in future between the racemic therapeutic or the single isomeric ballast-free drug will largely be based on a critical evaluation of the chiral characteristics with regard to their therapeutic, toxicological and pharmacokinetic aspects. PMID- 1743253 TI - Central and peripheral haemodynamic responses to felodipine in congestive heart failure. AB - Using non-invasive radionuclide techniques, we studied the arterial and venous effects of 0.1 mg/kg oral felodipine in 12 men with heart failure due to ischaemic heart disease aged 37-72 y. All were in New York Heart Association Class II or III, required frusemide 40-120 mg daily and were clinically stable. Felodipine produced significant falls in blood pressure (-19%) and systemic vascular resistance (-39%) with increases in cardiac index (+34%), heart rate (+12%) and left ventricular ejection fraction (from 0.25 to 0.32). Peripheral venous volume fell by 10.6% after felodipine indicating venoconstriction rather than venodilatation and may be caused by an acute sympathetic reflex associated with the increase in heart rate. Our results confirm that felodipine is an arterial vasodilator. The previously observed changes in cardiac filling pressures may simply represent improved ventricular function as a consequence of reduced afterload, not venodilatation. PMID- 1743254 TI - Acute haemodynamic effects of i.v. nitrendipine in healthy subjects. AB - The haemodynamic effects of an i.v. infusion of 2 mg nitrendipine have been studied in six healthy volunteers. Nitrendipine significantly decreased the systolic (-8.3%) diastolic (-19.9%) and mean arterial (-11.6%) blood pressures and the peripheral vascular resistance (-57.8%), and significantly increased leg blood flow (+128%). Stroke volume did not change. Due to the increase in heart rate (+28.5%), the cardiac output (2.8.2%) rose significantly. The haemodynamic effects were closely related to the serum nitrendipine concentration. The sigmoidal Emax-model was appropriate to describe the data. Pronounced interindividual differences in the serum nitrendipine concentrations required to elicit 50% of the maximum haemodynamic effect (EC50) were observed. The EC50 for the increase in leg blood flow ranged from 2.9 to 30.9 ng/ml and for the reduction in peripheral vascular resistance from 2.1 to 25.7 ng/ml. Interindividual differences in EC50 values were less pronounced if based on unbound serum nitrendipine levels. The fraction of nitrendipine not bound to serum proteins showed a three-fold difference between subjects, with free fractions ranging from 0.011 to 0.036. The unbound EC50 values for the increase in leg blood flow varied between 0.06 and 0.44 ng/ml and for the reduction in peripheral vascular resistance from 0.07 to 0.35 ng/ml. Based on the serum concentrations associated with comparable haemodynamic effects nitrendipine was at least three-times more potent than nifedipine. PMID- 1743255 TI - Rat retinal ganglion cells in culture. AB - A stable cell culture system of identified retinal ganglion cells would facilitate the investigation of cellular mechanisms of damage from glaucoma and other disorders. We have developed a reliable technique to culture retinal ganglion cells on a glial cells monolayer which extends viability and promotes extensive neurite outgrowth. Dissociated retinal cells from 5-7-day-old Sprague Dawley rats were cultured on glial monolayers derived from rat cerebral hemispheres. Retinal ganglion cells were labeled with retrograde fluorescent markers injected into the superior colliculus or in culture with monoclonal antibody to Thy-1 antigen. Since Thy-1 antigen is not entirely specific for retinal ganglion cells, and fluorescent markers fade in older cultures, the identity of Thy-1 marked cells was confirmed with whole-cell electrophysiologic recordings. Labeled, physiologically intact retinal ganglion cells were identified for at least 31 days in culture. Many retinal ganglion cells showed neurite elongation of 2 mm or more and developed complex intercellular networks. This cell culture system may be used to form the basis for future studies of the electrophysiology and transport properties of retinal ganglion cells under normal culture conditions and under adverse conditions such as those that mimic ischemia or mechanical deformation. PMID- 1743256 TI - Quantitation of ischemic damage in the rat retina. AB - In order to determine thresholds for irreversible cellular injury in the rat retina, timed acute no-flow ischemic episodes of 30-180 min duration were produced by elevation of intraocular pressure (IOP) above systolic pressure. Quantitation of irreversible degeneration and cell loss following a 2-week post ischemic interval was performed by computer-assisted measurements from histologic sections. Alterations of thickness of retinal layers and linear cell density were determined for ischemia of selected durations (30, 60, 80, 90, 120 and 180 min). Different thresholds were evident for inner and outer retinal damage. Neurons of the inner nuclear layers showed extensive loss with episodes at 60 min. Decrease in the thickness of the inner plexiform layer provided the best index of this inner nuclear damage. The outer retina was more resistant, with photoreceptors showing extensive damage only after 90 min in conjunction with pigment epithelial metaplasia and degeneration. Two-hour episodes produced full-thickness degeneration with loss of pigment epithelium and sparing of the peripheral retina. Greater sensitivity of the inner retina suggested problems with restoration of the retinal circulation. Horseradish peroxidase infusions did reveal central microcirculatory defects in retinal wholemounts of some specimens with episodes longer than 60 min. Refinements of the methods resulted in outcomes sufficiently reproducible for quantitative assessment of acute ischemic injury. The rat retina provides an economical basic tissue model of acute ischemic injury affecting neurons, glia, and microvasculature. Quantitation of this injury promises great utility in testing agents with potentially protective effects on acute ischemic injury. PMID- 1743257 TI - Muller glial cells of the goldfish retina are phagocytic in vitro but not in vivo. AB - The role of Muller glial cells in the process of degeneration and regeneration of the goldfish retina is poorly understood. One potential role is phagocytosis of neuronal debris in degenerating retinas. We investigated the phagocytic capacity of Muller glial cells of the goldfish retina both in vitro and in vivo. Muller glial cells from primary or first passage cultures were incubated with latex beads to assess their phagocytic ability, and acridine orange staining was used to identify phagolysosomes in living Muller glial cells. These experiments showed that Muller glial cells are phagocytic in culture. Cell identity was verified with an antibody raised against glial fibrillary acidic protein (GFAP). For the in vivo experiments fluorescent latex beads alone or in combination with the metabolic poison ouabain were injected into the posterior chamber. At various intervals (4 days to 8 weeks) after injection the retinas were prepared for immunocytochemistry. Polyclonal anti-GFAP and NN-1, a monoclonal antibody which recognizes macrophages and microglia within the goldfish retina, were used to identify the phagocytic cells. When the beads were injected into the eye, they were phagocytosed by macrophages/microglia cells but not by Muller cells. PMID- 1743258 TI - Effect of varying oxygen concentrations on the proliferation of retinal microvascular cells in vitro. AB - Microvascular fragments and pure cultures of either retinal microvascular endothelial cells, retinal pericytes or Tenon's capsule fibroblasts were grown on a gas permeable substrate while exposed to varying oxygen concentrations (5, 10, 20, 40 and 95% oxygen). For all three cell types cell proliferation was greatest under the lowest oxygen concentration and decreased as the oxygen concentration increased. The decrease in the proliferative ability of cells exposed to the higher oxygen concentrations could be reversed if the cells were returned to a normoxic environment. Endothelial cells were the most sensitive to changes in oxygen tensions showing a proliferative response after 24 hr exposure as opposed to 48 hr for pericytes and fibroblasts. These results suggest a direct mechanism by which the intra-vitreal and intra-retinal oxygen tension may influence both the development of preretinal new vessels (in response to retinal ischaemia) and also the regression of neovascularization following scatter photocoagulation or vitrectomy. PMID- 1743259 TI - Interferon-gamma induces the expression of major histocompatibility antigens by human retinal glial cells. AB - Retinal glial cells normally do not express major histocompatibility (MHC) molecules. However, the expression of MHC antigens by retinal glial cells under certain pathological conditions suggests that these cells may play a role in immune responses of the retina. At present, the identity of molecules that may regulate the expression of class I and class II MHC antigens by retinal glial cells has not been established. Since interferon-gamma (IFN-gamma) induces MHC antigens in a variety of cell types, we examined the effect of this lymphocyte product on class I and class II antigen expression by human retinal glial cells in culture. Glial cells derived from post-mortem donor eyes were exposed to recombinant human IFN-gamma. Cells with MHC class I or class II antigens were detected with the use of specific monoclonal antibodies that were labeled directly or indirectly with fluorescent probes. Fluorescence of labeled cells was assayed by flow cytometry. Exposure to IFN-gamma increased the expression of class I and class II antigens by the retinal glial cells. Double labeling studies showed that 90% of the glial cells induced to express class II antigens also had class I antigens. Overall, the results show that IFN-gamma can regulate the expression of MHC molecules by human retina glial cells in culture. These findings are consistent with the concept that glia may play a role in immunological disorders affecting the retina. PMID- 1743260 TI - Post-translational arginylation in the bovine lens. AB - This study demonstrates post-translational arginylation of bovine serum albumin and endogenous lens proteins by bovine lens arginyl-tRNA:protein transferase. This reaction has been proposed to be the first step in marking specific proteins for degradation by the non-lysosomal, ATP-dependent, ubiquitin-mediated proteolytic pathway. The transferase was obtained by the method used for isolation of the same enzyme from reticulocytes (Ferber and Ciechanover, 1987, Nature 326, 808-11). Incorporation of [3H]Arg was linear for at least 2 hr at 37 degrees C. The amount of incorporation was directly proportional to the amount of lens enzyme or substrate added. Arginylation was ATP-dependent. A requirement for tRNA was demonstrated by inhibition upon pretreatment of the enzyme preparation with nuclease to hydrolyse endogenous tRNA, and restoration of activity upon replacement of tRNA. [3H]Leu, [3H]Lys and [3H]His were not incorporated, demonstrating specificity of the reaction for arginine. This is the first demonstration of post-translational modification of proteins by arginylation in the lens. PMID- 1743261 TI - Autoradiographic, electrophoretic, and immunocytochemical studies of glycoproteins of the rabbit iris. AB - L-[3H]fucose was injected either intravitreally or intra-aqueously into adult rabbits which were killed at several time points after injection. SDS polyacrylamide gel electrophoresis and fluorography of iris extracts revealed that most of the proteins are glycoproteins containing fucose residues. Autoradiography of semi-thin histologic sections demonstrated that glycoprotein synthesis was most prominent in the epithelium of the iris, while little protein synthesis was evident in the stroma of the iris. The results of these experiments indicated that the glycoproteins of the iris undergo renewal. The protein band pattern of the iris extracts was very similar to that of extracts of the ciliary body. The high-molecular-weight cartilage matrix glycoprotein (CMGP), an intrinsic component of the ciliary body, vitreous, and aqueous humor, was detected by immunohistologic studies only in the stroma of the iris. The results of immunohistochemical analyses of the eyes of young rabbits (1-21 days old), in addition to the autoradiographic findings, strongly suggest that CMGP is not an intrinsic glycoprotein of the iris stroma, at least in this species. PMID- 1743262 TI - Abnormalities of the electroretinogram and visual-evoked potential in vitamin E deficient rats. AB - Flash electroretinograms, retinal oscillatory and cortical visual-evoked potentials were recorded in 10-month vitamin E deficient rats and in age-matched controls. A significant increase in the latency (P less than 0.0001) and decrease in amplitude (P less than 0.0001) of the electroretinogram a- and b-waves were observed in the vitamin E deficient rats compared with controls. The vitamin E deficient rats also showed a significant delay (P less than 0.002) in early oscillatory potentials. No significant group differences were obtained in the P1 latency or P1-N1 amplitude of the visual-evoked potential; however, the N1 peak was significantly delayed (P = 0.01) in the vitamin E deficient rats. This study shows, for the first time, that the electroretinogram and visual-evoked potential to flash stimulation provide a sensitive index for monitoring the visual effects of vitamin E deficiency in the rat. PMID- 1743263 TI - Mapping of Fc gamma receptors in the human and porcine eye. AB - By using an immunohistochemical technique, we detected a strong reaction product for Fc gamma receptors in the keratoconjunctival epithelium, uveal trabecular meshwork, optic nerve, and muscle walls of the retinal and ciliary vessels of infant human eyes; moderate staining was seen on the corneal endothelium, corneoscleral trabecular meshwork, non-pigmented ciliary epithelium, ciliary muscle fibers, endothelial lining of ocular blood vessels, as well as the anterior region of Muller cells, the outer nuclear layer, and pigment epithelium of the retina. In aged human and porcine eyes, the same structures stained somewhat less intensely than did those in infant human tissues. Primary cultures of porcine trabecular cells demonstrated a more intense immunoreaction product than did tertiary cultures. We discuss the possible role of Fc gamma receptors in various ocular inflammatory conditions and the implications of age-dependent expression by human trabecular cells in the pathogenesis of open-angle glaucoma. PMID- 1743264 TI - Mitogenic effects of excitatory amino acids in the adult rat retina. AB - We studied the retinas of adult rats after the intravitreal injection of excitatory amino acids and ouabain. Kainic acid, domoic acid, N-methyl D-asparate and ouabain produced swelling and vacuolization of the outer plexiform, inner nuclear and inner plexiform layers and pyknosis. Mitoses were present in retinas treated with all agents other than N-methyl D-asparate. Rompun ketamine anesthesia blocked the mitogenic effects. Immunohistochemical labeling of both glial fibrillary acidic protein and S100 protein would indicate that the mitoses are occurring in glial cells. We suggest that the mitogenic effects are mediated through action on glial cationic channels, and might account for the reactive gliosis observed in some retinal lesions. PMID- 1743265 TI - In utero and milk-mediated effect of aldose reductase inhibitor on galactose cataracts. AB - Our previously reported investigations showed that cataracts could be induced in fetal lenses through the maternal feeding of galactose during pregnancy. We also reported that the lens opacity present at birth reverses completely by 30 days of age if there is no further post-natal exposure to galactose. This investigation was designed to investigate if an aldose reductase inhibitor (ARI) has any cross placental effect in preventing galactose-induced cataracts in fetuses. We have also evaluated if there are any milk-mediated effects of galactose on cataract induction and of galactose and ARI on the maintenance or reversal of opacities induced in utero. Pregnant Sprague-Dawley rats were fed either 50% galactose or rat chow with or without the ARI, (2R,4S)-6-fluoro-2-methyl spirochroman-4,4' imidazolidine-2',5'-dione (Eisai compound E-0722). Following parturition, pups of mothers from the different dietary groups were either fed by their own mothers or foster fed by lactating females fed either rat chow or 50% galactose with or without the ARI. Lenses of the pups were examined at desired intervals with light and scanning electron microscopes. We observed that: (a) both galactose and the ARI had a cross-placental effect on the fetal lenses in the development and inhibition of cataracts, respectively; (b) galactose had very little, if any, milk-mediated effect on either the induction of cataracts in newborn pups that were born with transparent lenses or the maintenance of cataracts induced in utero; (c) the ARI appeared to have a milk-mediated effect, which accelerates the reversal of cataract associated alterations in lenses of pups with cataracts induced in utero, leading to further reinstatement of lens transparency; and (d) the presence of ARI in the diet of rats during pregnancy and/or post-parturition provided continued protection to the lenses of pups that were exposed to a galactose diet following birth. PMID- 1743266 TI - Cellular expression of collagen IV mRNA in eye. PMID- 1743267 TI - Influence of bicarbonate and insulin on pigment synthesis by cultured adult human retinal pigment epithelial cells. PMID- 1743268 TI - S cone-driven but not S cone-type electroretinograms in the enhanced S cone syndrome. PMID- 1743269 TI - HIV tests costs exceed benefits. PMID- 1743270 TI - Targeted HIV screening fails. PMID- 1743271 TI - Family planning clinics: facing higher costs and sicker patients. AB - Family planning clinics throughout the United States are facing a variety of obstacles that threaten their ability to provide necessary contraceptive services to low-income women and teenagers, according to interviews with clinic administrators. In the last few years, the proportion of patients coming to family planning agencies in need of screening or treatment for sexually transmitted diseases (STDs) has increased dramatically. Many providers report that 10-15 percent of their clients are infected with chlamydia, the most prevalent STD. The increasing costs of Pap tests and contraceptives are also major problems: As a result of recent federal legislation, the price of Pap tests has risen substantially, and that of contraceptives is beginning to increase steeply. Finally, Title X funding for family planning services has decreased 66 percent over the last decade if both cuts and inflation are taken into account. As a result of the squeeze between increased costs and decreased public funding, clinics have been forced to charge higher fees, maintain long waiting lists for appointments and curtail community outreach. In addition, growth of the family planning patient population has slowed dramatically, and even declined, in some places. PMID- 1743272 TI - Public funding of contraceptive, sterilization and abortion services, fiscal year 1990. AB - In FY 1990, the federal and state governments spent $504 million to provide contraceptive services and supplies, according to results of a survey of state health, social services and Medicaid agencies conducted by The Alan Guttmacher Institute. Medicaid accounted for 38 percent of all public funds spent on contraceptive services, Title X provided 22 percent, and two federal block-grant programs--Social Services and Maternal and Child Health--together were responsible for 12 percent of public expenditures. State governments accounted for the remaining 28 percent of public funding. Although public expenditures for contraceptive services have risen by $154 million over the past decade, when inflation is taken into account, expenditures have actually fallen by one-third. Since 1980, the proportion of public contraceptive expenditures contributed by Title X has been cut virtually in half, while the proportion contributed by state governments has nearly doubled. When inflation is taken into account, Title X expenditures for contraceptive services have fallen by almost two-thirds since 1980. The federal and state governments together spent $95 million to subsidize sterilization services in 1990, and $65 million to provide abortion services. The federal government was the major source of funding for sterilization services but provided less than one percent of the cost of abortion services. Because of changes over time in survey methodology and the difficulties some states had in separating out expenditures by type of care, these data are approximations. PMID- 1743273 TI - Determinants of unintended childbearing among ever-married women in the United States: 1973-1988. AB - A downward trend in unwanted childbearing has reversed among large segments of the population, according to data from the 1988 National Survey of Family Growth. The proportion of births in the previous five years that were unwanted at conception fell from 14 percent in 1973 to eight percent in 1982, but increased to 10 percent in 1988. Between the 1982 and 1988 surveys, increases were most pronounced among women with less than a high school education and among women living below the federal poverty level. Differences between black women and white women in levels of unwanted childbearing, which were converging prior to 1982, have since grown considerably, particularly among the poor and the less educated. PMID- 1743274 TI - Testing for sexually transmitted diseases among women of reproductive age: United States, 1988. AB - Approximately 13.3 million women aged 15-44--about 26 percent of all women of reproductive age who had ever had intercourse--were tested for sexually transmitted diseases (STDs) in the 12 months before the 1988 National Survey of Family Growth. Slightly over half of the women tested received the test as part of a family planning visit. Women who used clinics for family planning services were most likely to be tested--54 percent compared with 34 percent of women who used a private doctor for family planning and 16 percent of women who did not receive family planning services that year. The findings suggest that access to medical care, especially access to family planning clinics, has strong effects on a woman's chances of being screened for STDs, independent of her individual characteristics. The most important individual characteristic affecting the chance of being tested for an STD was race: About 47 percent of black, 27 percent of Hispanic, and 23 percent of white and other women were tested in the 12 months before the survey. Among groups with high-risk behaviors, only 34 percent of sexually experienced teenagers were screened for STDs in the past year, as were only 43 percent of women with a positive STD history and 32 percent of women with 10 or more lifetime partners. PMID- 1743275 TI - Condom use with regular and casual partners among women attending family planning clinics. AB - A survey of 16,632 women attending family planning clinics in Pennsylvania found that only 13 percent of the sample used condoms. Moreover, 67 percent of the women with regular partners never used condoms with those partners, and 72 percent of women who had casual partners never used them with those partners. Levels of condom use with both regular and casual partners were higher among women younger than 20, those who were nonwhite, those with multiple partners and those who reported a previous STD infection. However, women who had sex partners who used intravenous drugs were less likely to use condoms with regular or casual partners than were women who did not have drug-using partners. PMID- 1743276 TI - Efficacy of the simultaneous use of condoms and spermicides. PMID- 1743277 TI - A future for Title X? PMID- 1743278 TI - Abortion underreporting. PMID- 1743279 TI - Transduction of enzyme-ligand binding energy into catalytic driving force. AB - We propose a testable general mechanism by which ligand binding energy can be used to drive a catalytic step in an enzyme catalyzed reaction or to do other forms of work involving protein molecules. This energy transduction theory is based on our finding of the widespread occurrence of ligand binding-induced protein macrostate interconversions each having a large invariant delta H0 accompanied by a small but highly variable delta G0. This phenomenon, which can be recognized by the large delta Cp0's it generates, can provide the necessary energy input step but is not in itself sufficient to constitute a workable transduction mechanism. A viable mechanism requires the additional presence of an 'energy transmission step' which is terminated to trigger the 'power' stroke at a precise location on the reaction coordinate, followed by an energetically inexpensive 'return' step to restore the machine to its initial conditions. In the model we propose here, these additional steps are provided by the existence of ligand inducible 2-state transitions in the free enzyme and in each of the enzyme complexes that occur along the reaction coordinate, and by the selective blocking of certain of these interconversions by high energetic barriers. We provide direct experimental evidence supporting the facts that these additional mechanistic components do exist and that the liver glutamate dehydrogenase reaction is indeed driven by just such machinery. We describe some aspects of the chemical nature of these transitions, and evidence for their occurrence in other systems. PMID- 1743280 TI - Identification of the phosphorylation sites of H2B histone by a catalytic fragment of p72syk from porcine spleen. AB - Phosphorylated sites of calf thymus H2B histone were investigated with a catalytic fragment of 72 kDa protein-tyrosine kinase (p72syk). Three of five tyrosine residues in H2B histone can be phosphorylated by this kinase. In this analysis, H2B histone was thoroughly phosphorylated in vitro with [gamma-32P]ATP and the kinase, and then digested with a lysylendopeptidase. The resulting radioactive phosphopeptides were separated by a reverse-phase column on high performance liquid chromatography. Subsequent sequential Edman degradation of the purified phosphopeptides revealed that 40Y, 83Y and 121Y were phosphorylated. 121Y is the major phosphorylated residue in H2B histone. No phosphorylation was detected in 37Y and 42Y. Although the consensus sequence was not defined from these analyses, our data suggest that higher-order structure(s) in addition to primary one may participate in recognition of H2B histone by this protein kinase. PMID- 1743281 TI - Striking structural and functional similarities suggest that intestinal sucrase isomaltase, human lysosomal alpha-glucosidase and Schwanniomyces occidentalis glucoamylase are derived from a common ancestral gene. AB - Sequence comparison of the primary structure of the yeast Schwanniomyces occidentalis glucoamylase (GAM) with GAMs in different microorganisms did not reveal significant similarities. By contrast, striking similarities were, surprisingly, found with 3 mammalian secretory and integral membrane proteins: the 2 subunits of intestinal brush border sucrase-isomaltase and human lysosomal alpha-glucosidase. The similarities among these proteins are found as clusters of up to 8 amino acids and distributed all over the protein sequences. The major sequence differences are found in the N-terminal regions accounting, probably, for the different cellular locations of these proteins. The high level of similarities between sucrase, isomaltase, Sch. occidentalis GAM and human lysosomal alpha-glucosidase suggest that these proteins are derived from the same ancestral gene. To our knowledge, this is the first report that describes similarities between a yeast secretory protein and mammalian secretory and integral membrane proteins. PMID- 1743282 TI - Phosphorylation of alpha-crystallin B in Alexander's disease brain. AB - The phosphorylation of alpha-crystallin B was studied in homogenates of autopsy samples of brain tissue from patients with Alexander's disease, a condition characterized by over-expression of this protein. After incubation in the presence of [gamma-32P]ATP and cAMP the homogenates were analyzed by two dimensional electrophoresis, (isoelectric focusing followed by SDS-PAGE). Three major polypeptides having the same molecular weight as bovine lens alpha crystallin B and pIs 7.1, 6.9 and 6.7 were detected in the Coomassie blue stained gels. These three polypeptides were recognized by an alpha-crystallin B-specific antiserum in Western blots. The polypeptides with pIs 7.1 and 6.7 co-migrated in isoelectric focusing gels with bovine lens alpha B and its phosphorylated form alpha Bp, respectively. Radioautography of the two-dimensional gels demonstrated the presence of 32P in the most acidic polypeptide. The results demonstrate the occurrence of alpha B phosphorylation in Alexander's disease brain tissue. PMID- 1743283 TI - Purification and characterization of a Kunitz-type trypsin inhibitor from Leaf nosed viper venom. AB - A Kunitz-type trypsin inhibitor was purified from Leaf-nosed viper venom and the primary structure determined by peptide analysis. In relation to other trypsin inhibitors, the protein has an extended C-terminal segment and a distinct pattern of residue alterations at the functionally important contact sites with proteases. PMID- 1743284 TI - Catalytic fragment of protein kinase C exhibits altered substrate specificity toward smooth muscle myosin light chain. AB - Smooth muscle myosin light chain (LC) can be phosphorylated by myosin light chain kinase (MLCK) at Ser19 and Thr18 and by protein kinase C (PKC) at Thr9 and Ser1 or Ser2 under the in vitro assay conditions. Conversion of PKC to the spontaneously active protein kinase M (PKM) by proteolysis resulted in a change in the substrate specificity of the kinase. PKM phosphorylated both sets of sites in LC recognized by MLCK and PKC as analyzed by peptide mapping analysis. The PKM catalyzed phosphorylation of these sites was not greatly affected by a MLCK inhibitor, ML-9, nor by the activators of MLCK, Ca2+ and calmodulin. PMID- 1743285 TI - Ca2+ binding properties of type X collagen. AB - Type X collagen is a developmentally regulated collagen that is only synthesized by chondrocytes of the hypertrophic and calcifying zone in fetal cartilage. There is evidence in the literature that type X collagen may be involved in cartilage calcification. Here we show that type X collagen synthesis precedes calcium deposition in nodules of fetal human chondrocytes forming in cell culture and present evidence that type X collagen binds calcium in a specific and dose dependent manner. In an assay using bovine type X collagen coupled to beads and 45Ca2+ we determined a total of about 15 binding sites per alpha 1(X) chain with a dissociation of 32 microM. PMID- 1743286 TI - An impaired peroxisomal targeting sequence leading to an unusual bicompartmental distribution of cytosolic epoxide hydrolase. AB - To gain an understanding of the mechanism by which the subcellular distribution of cytosolic epoxide hydrolase (cEH) is directed, we have analyzed the carboxy terminal region of rat liver cEH by means of cDNA cloning to define the structure of its possible peroxisomal targeting sequence (PTS). Purified cEH was subjected to peptide analysis following endoproteinase Glu-C digestion and HPLC-separation of the fragments. The obtained sequence information was used to perform PCR experiments resulting in the isolation of a 680 bp cDNA clone encoding the carboxy terminus of cEH. The deduced amino acid sequence displays a terminal tripeptide Ser-Lys-Ile which is highly homologous to the PTS (Ser-Lys-Leu) found in other peroxisomal enzymes. This slight difference appears to be sufficient to convert the signal sequence into an impaired and therefore ambivalent PTS, directing the enzyme partly to the peroxisomes and allowing part to reside in the cytosol. PMID- 1743287 TI - Immunological identification and sequence characterization of a peptide derived from the processing of neuroendocrine protein 7B2. AB - A newly raised antiserum against the C-terminal region of neuroendocrine protein 7B2 was used to purify a novel peptide from the culture media of the mouse corticotroph cell line AtT-20. Based on partial sequencing, this peptide, which we call Cter-7B2, begins at Ser156 and appears to result from the cleavage of pro7B2 after a five-basic-residue sequence. Thus, 7B2 processing may contribute to the diversity of peptides found in neuronal and endocrine cells. PMID- 1743288 TI - Mechanism of maturation and nature of carbohydrate chains of boar sperm acrosin. AB - The acrosin zymogen proacrosin exists in two molecular forms which are believed to be single-chain polypeptides. During autoactivation in a cell-free system, the 55 and 53 kDa zymogens are sequentially converted into the 49, 36, 31 and 25 kDa forms. A similar mechanism of maturation was revealed, when the calcium ionophore A23187 was added to suspensions of boar spermatozoa. The 49 kDa form has been identified as the first active acrosin form in the maturation cascade. However, this form is indistinguishable from the 53 kDa zymogen in SDS-PAGE at nonreducing conditions. Two carbohydrate chains were evidenced on the acrosin molecule. The chain attached to the Asn3 of the acrosin light chain was enzymatically cleaved without loss of acrosin activity. By contrast, the carbohydrate chain linked to the acrosin heavy chain could be cleaved only after acrosin denaturation. Based on the susceptibility of acrosin to endoglycosidases F and H, a biantennary structure of both carbohydrate chains is proposed. PMID- 1743289 TI - The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide. AB - This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferryl myoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferryl myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferryl myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide. PMID- 1743290 TI - In vivo study of the state of order of the membranes of gram-negative bacteria by Fourier-transform infrared spectroscopy (FT-IR). AB - Temperature-induced order/disorder transition profiles were obtained from the membranes of intact Gram-negative bacterial cells by FT-IR analysis of the frequency shifts of the acyl chain methylene symmetric stretching band as a monitor. Cells grown at different temperatures yielded distinct transition profiles. At the individual growth temperatures, however, the nearly alike frequency values indicated a very similar 'state of order' of the bacterial membranes. The FT-IR data were complemented by GC analysis of whole cell fatty acid composition. The FT-IR data obtained in vivo gave direct evidence of the adaptation of the 'state of order' and 'fluidity' of bacterial membranes to varying growth temperatures. PMID- 1743291 TI - Purkinje cells of rat and chicken cerebellum contain calreticulin (CaBP3). PMID- 1743292 TI - The 3' promoter region involved in RNA synthesis directed by the turnip yellow mosaic virus genome in vitro. AB - We have previously shown that the last 100 nucleotides from the 3' end of turnip yellow mosaic virus (TYMV) RNA compete in vitro with genomic RNA for the TYMV specific RNA-dependent RNA polymerase (RdRp). To further characterize the promoter on genomic RNA that produces complementary RNA strands, shorter fragments corresponding to the 3' region of the viral RNA were generated and used in in vitro assays. Fragments as short as 38 nucleotides corresponding to the 3' end of TYMV RNA compete with the viral RNA for the RdRp suggesting that the 3' promoter on plus strand RNA is probably less than or equal to 38 nucleotides long. These transcripts are themselves used as templates in vitro. PMID- 1743293 TI - Histone H1 and the regulation of transcription by nuclear receptors. AB - Histone H1 is a eukaryotic repressor which recognizes specific DNA structures, and nucleotides regulate its interaction with DNA. Since their mode of action may be considered similar to that observed in the case of plasma membrane GTPases, H1 may be regarded as an ATP/GTPase involved in the action of nuclear receptors. A hypothesis is put forward here to suggest that transcriptional activators CTF/NF I and AP-1 (fos/jun), for example, are effectors for H1. H1 and CTF/NF-I may be members of a stimulatory regulatory cascade for nuclear receptor action that ends with selective activation of chromatin through histone modification and the disruption or a more subtle structural change of a specific nucleosome, while an opposite effect may be obtained through modification of fos/jun by H1. PMID- 1743294 TI - Structure of the active 27-residue fragment of human calpastatin. AB - A synthetic 27-residue peptide corresponding to exon 1B of the endogenous inhibitor calpastatin contains a well-conserved region and has an ability to inhibit the cysteine endopeptidase calpain specifically. We examined the solution structure of this peptide in DMSO-d6 by two-dimensional 1H NMR spectroscopy. Although regular secondary structures such as alpha-helix and beta-sheet were not found, the region from Ile18 to Arg23 formed a well-defined structure with a type I beta-turn. This region coincided well with the highly conserved region of calpastatin. The result strongly suggests that this turn structure is essential for the inhibitory activity of calpastatin. PMID- 1743295 TI - Different types of microsomal enzymes catalyze ortho- or para-hydroxylation in the biosynthesis of carnation phytoalexins. AB - Cell suspension cultures of carnation (Dianthus caryophyllus L.) accumulate, upon challenge with crude fungal elicitor, various dianthramide phytoalexins, all of which derive from N-benzoylanthranilate. In vitro, microsomes from the elicited carnation cells hydroxylated N-benzoylanthranilate in the 4- and/or 2'-positions to yield the hydroxyanthranilate and/or salicyloyl derivatives. 2'-Hydroxylation was shown to precede 4-hydroxylation in the formation of N-salicyloyl-4 hydroxyanthranilate, and both these activities depended strictly on NADPH and molecular oxygen. 4-Hydroxylation was shown to be catalyzed by cytochrome P-450 dependent monooxygenase(s), whereas the 2'-hydroxylating activity appeared to be due to a novel class of enzymes, also responding synergistically to NADH in combination with NADPH and showing apparent inhibition by cytochrome c but not by carbon monoxide. The difference in type of 4- and 2'-hydroxylases was corroborated by the exclusive inhibition of either activity in imidazole vs. MOPS buffers as well as their differential heat sensitivities. In the course of these studies, low concentrations of N-salicyloylanthranilate turned out to inhibit the cytochrome P-450-dependent 4-hydroxylation more strongly than any of the commercial inhibitor chemicals tested, while neither the substrate, N benzoylanthranilate, nor the final product, N-salicyloyl-4-hydroxyanthranilate, exhibited such significant inhibition. In addition, 2'-hydroxylation activity was affected much less by N-benzoylanthranilate, N-salicyloylanthranilate or by inhibitor chemicals. The results demonstrate the requirement of two different classes of hydroxylase activities that appear to introduce the antimycotic quality to the dianthramides for phytoalexin defense. PMID- 1743296 TI - Inhibition of protein kinase C is associated with a decrease in c-myc expression in human myeloid leukemia cells. AB - Treatment of human myeloid leukemic cells with phorbol esters such as 12-O tetradecanoylphorbol-13-acetate (TPA) is associated with activation and then partial down-regulation of protein kinase C activity. Previous work has suggested that the activation of protein kinase C by TPA contributes to the decrease in c myc expression during differentiation of these cells. The present studies demonstrate that the decline in c-myc mRNA levels following exposure of HL-60 cells to TPA is preceded by an increase in expression of this gene. In contrast, exposure of HL-60 cells to inhibitors of protein kinase C activity is associated with down-modulation of c-myc expression. Similar findings have been obtained in U-937 myeloid leukemia cells. Taken together, these findings suggest that phorbol esters have a biphasic effect on c-myc expression. Whereas the activation of protein kinase C by phorbol esters may be associated with an increase in c-myc gene expression, the subsequent partial down-regulation of kinase activity may initiate a cascade of events resulting in the down-modulation of c-myc expression. PMID- 1743297 TI - Identification of a 220 kDa membrane-associated plant cell protein immunologically related to human beta-spectrin. AB - Electrophoretic analysis of low ionic strength extracts of tomato plant leaves revealed the presence of two proteins of apparent molecular weights of 240 kDa and 220 kDa which co-migrated with purified human erythrocyte alpha- and beta spectrin subunits. Immunochemical analyses employing an affinity-purified polyclonal antibody to human erythrocyte beta-spectrin reacted specifically with the 220 kDa plant cell protein. Immunofluorescence microscopy indicated that the beta-spectrin antibody recognized an antigen which was primarily restricted to the peripheral areas of the cells. Collectively, these results suggest that the cells of higher plants contain polypeptides related to the spectrin family of proteins. It is proposed that the plant cell possesses a membrane skeleton which is structurally and perhaps functionally analogous to that of the animal cell. PMID- 1743298 TI - 1H, 13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site. AB - The backbone 1H, 13C and 15N chemical shifts of cyclophilin (CyP) when bound to cyclosporin A (CsA) have been assigned from heteronuclear two- and three dimensional NMR experiments involving selectively 15N- and uniformly 15N- and 15N,13C-labeled cyclophilin. From an analysis of the 1H and 15N chemical shifts of CyP that change upon binding to CsA and from CyP/CsA NOEs, we have determined the regions of cyclophilin involved in binding to CsA. PMID- 1743299 TI - A unique vacuolar processing enzyme responsible for conversion of several proprotein precursors into the mature forms. AB - Proprotein precursors of vacuolar components are transported from the endoplasmic reticulum into vacuoles, where they are proteolytically processed into their mature forms. However, the processing mechanism in plant vacuoles is very obscure. Characterization of a purified processing enzyme is required to determine whether a single enzyme is responsible for processing many vacuolar proteins with a large variability of molecular structure. If this is true, how can it recognize the numerous varieties of processing sites? We have now purified a processing enzyme (Mr = 37,000) from castor bean seeds. Our results show that the purified enzyme can process 3 different proproteins isolated from either the endoplasmic reticulum or transport vesicles in cotyledon cells to produce the mature forms of these proteins which are found at different suborganellar locations in the vacuole: the 2S protein found in the soluble matrix, the 11S globulin found in the insoluble crystalloid and the 51 kDa protein associated with the membrane. Thus a single vacuolar processing enzyme is capable of converting several proprotein precursors into their respective mature forms. PMID- 1743300 TI - Demonstration of L1-related mRNAs in rat brain using DNA oligonucleotide probes. AB - Only one copy of the cell adhesion molecule L1 gene is present in the mouse genome, and only one mRNA of 6 kilobases (kb) is expressed in mouse brain [1987, Neurosci. Lett. 82, 89-94]. We have constructed 5 synthetic oligonucleotide probes covering different parts of the published mouse L1 cDNA sequence. Using these probes 3 distinct mRNAs of 9.0, 7.0 and 6.0 kb in rat brain could be demonstrated. Hybridizations performed at different stringency conditions indicated that the 9.0 and 7.0 kb mRNAs were highly related to the L1 mRNA of 6.0 kb expressed in rat brain. The 7.0 kb mRNA is possibly coding for a rat homologue of chicken Nr-CAM, whereas the 9.0 kb mRNA may code for a new member of the L1 family. PMID- 1743301 TI - The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw. PMID- 1743302 TI - Surgical oncology in Poland. PMID- 1743303 TI - Ten years of experience with Parks' coloanal sleeve anastomosis for the treatment of post-irradiation rectovaginal fistula. AB - Twenty-four cases of coloanal sleeve anastomosis for the repair of rectovaginal post-irradiation fistula are described. All patients were previously irradiated because of carcinoma of the uterine cervix. Eleven patients had simultaneous repair of vesicovaginal fistula. One postoperative death was observed. Of the 23 surviving patients, functional results were good in 18. In 16 patients with difficult stripping of the rectal mucosa, surgical curettage was performed. The latter procedure is suggested as a useful method in relevant cases. PMID- 1743304 TI - Surgical and cryosurgical salvage of oral and oropharyngeal cancer recurring after radical radiotherapy. AB - The results of salvage surgery or cryosurgery performed in 62 cases of oral or oropharyngeal cancer, recurring or persisting after radical radiotherapy, were analysed retrospectively. Salvage surgery was performed in 33 cases. The relatively high frequency of postoperative complications observed in years 1973 1984, has declined since 1985, concomitant with the introduction of myocutaneous flaps for reconstruction. Twenty-nine patients who were disqualified from major surgery, were treated by cryosurgery. Using both methods, 3-year overall survival was obtained in 24.1% of cases. PMID- 1743305 TI - Preoperative radiotherapy combined with resection of squamous cell carcinoma of the mid-thoracic oesophagus. Does a histopathological malignancy grading system assess actual survival? AB - The aim of our study was to assess the reproducibility of the findings of Hambraeus et al. In their group of patients with squamous cell carcinoma of the oesophagus who underwent preoperative radiotherapy and resection, the histopathological malignancy grading score system was found to predict survival. We studied nine patients with squamous cell cancer of the mid-thoracic oesophagus, who had received radiotherapy followed by surgery and survived over 12 months. We did not confirm the prognostic value of the histopathological malignancy grading score system. PMID- 1743306 TI - Preoperative concurrent chemotherapy and radiotherapy for local-regional and advanced squamous cell carcinoma of the thoracic oesophagus: preliminary results of a pilot study. AB - Preliminary experience based on the results of a pilot study on preoperative concurrent continuous i.v. infusion chemotherapy and radiotherapy for squamous cell carcinoma of the oesophagus in eight consecutive patients is presented. Chemotherapy consisted of 5-fluorouracil and cisplatin. Radiotherapy (Co-60) was delivered to a total dose of 3000 cGy. Clinical tolerance was good in four of eight patients, but poor in the remaining four, including three septic deaths. Oesophagectomy was performed in five patients with no postoperative deaths. Postoperative complications (Horner syndrome, hydrothorax, abdominal wound dehiscence) were observed in three cases. The response was categorized as complete (CR), partial (PR) or stable disease (SD), based on a comparison of the initial and immediate preoperative imaging studies and on the presence of tumour degeneration and/or necrosis in pathological examination of operative specimens. CR was observed in 1/8 patients, PR in 4/8 and SD in 3/8. Concurrent preoperative chemo- and radiotherapy may be effective as a neo-adjuvant or remission-inducing modality in the combined treatment of oesophageal carcinoma, however, it may also lead to fatal complications. PMID- 1743307 TI - Surgical delay of TRAM flaps for breast reconstruction. AB - The lower transverse rectus abdominis myocutaneous (TRAM) flap may give excellent results in breast reconstruction using autogenous tissues alone, however, surgical technique is demanding, and the risk of necrosis owing to vascular failure is high. We observed excellent vascularity of the flap in all 20 cases operated upon so far; in all these cases skin island was surgically delayed for one week before final transfer. PMID- 1743308 TI - The application of continuous thoracic epidural anaesthesia in outpatient oncological and reconstructive surgery of the breast. AB - The use of continuous thoracic epidural anaesthesia allows several oncological and reconstructive operations of the breast to be performed on an outpatient basis. The method is easy and safe in the hands of an experienced anaesthetist, and the recovery is immediate. The potential side effects (transient haemodynamic changes) may result from the sympathetic blockade and can be easily controlled during the operation. The method is not advocated in cases in which substantial blood loss is anticipated. PMID- 1743309 TI - Preoperative chemotherapy in primarily inoperable cancer of the breast. AB - One hundred and sixty patients with primarily inoperable breast cancer entered the preoperative chemotherapy protocol. The majority of patients (156) received chemotherapy according to the Cooper regimen (CMFVp), the remaining four were treated by the FAC regimen. Subsequently, mastectomy was performed in all patients. Postoperative treatment was chosen according to the hormonal status: premenopausal patients received chemotherapy (CMF), postmenopausal, hormonotherapy (tamoxifen). Overall 3 and 5-year survival rates were 58% and 38%, respectively. The degree of degeneration of cancer cells was estimated. Five-year overall survival rate in patients with significant cancer cell degeneration (greater than 75%) was higher, compared with patients without cancer cell degeneration (68% vs 33%, respectively P less than 0.002). We conclude that chemotherapy does not increase the rate of postoperative complications, and that the degeneration of cancer cells found in the specimen is an important factor with respect to improved survival. PMID- 1743310 TI - Breast cancer in elderly women: characteristics of the disease. AB - The records of 325 women aged over 70 years, with breast cancer were reviewed to identify the characteristics of the disease in elderly women and to determine the eventual effect of age on its management. Over 50% of patients were in the advanced stage (stage III or IV). The percentage of inoperable cases increased with greater delay between the onset of first symptoms and the first medical consultation (Chi-square (chi 2) = 42.8 P less than 0.001), but the delay time did not influence relative survival rates. Axillary lymph node status, stage of the disease and recurrences were the major factors influencing survival. Postoperative complications were analysed. Other, co-existing diseases were found in a significant number of patients (145, 44.6%); they did not influence long term results but increased postoperative mortality and morbidity. We conclude that breast cancer in elderly women can be treated by appropriate surgical therapy if the patient's overall performance status is good. Advanced age alone is not a contra-indication to the relevant therapy, corresponding with the stage of the disease. PMID- 1743311 TI - Early experience with 'fish-shaped' incision for mastectomy. AB - Early experience with the modified transverse incision for mastectomy is presented. A 'fish-shaped' incision, by adding two triangles at the lateral tip, decreases the amount of excess skin and prevents the 'dog ear' deformity, makes up the difference in the length of the transverse edges depending on the location of the tumour and provides easy access to the axilla. PMID- 1743312 TI - Differential diagnosis of thyroid tumours. An immunocytochemical study. AB - Fifty-seven patients with thyroid tumours, 11 malignant lymphomas, 12 follicular, eight papillary and 26 medullary carcinomas, were studied. HE stained sections and immunocytochemical reactions with mono- and polyclonal antibodies were evaluated. The usefulness of thyroglobulin staining in differential diagnosis of infiltrations and metastases was stressed. The group of medullary carcinomas was morphologically polymorphic and presented unexpected patterns of immunoreactivity. Recent embryological findings were discussed providing better understanding of this group of carcinomas. The presence of thyroglobulin, along with other markers in areas of medullary carcinoma in polymorphic tumours, and the presence of neuro-endocrine markers in areas of follicular or papillary differentiation seem to be concordant with the theory of a pluripotential cell, derived from neural crest and capable of differentiation into a variety of forms. PMID- 1743313 TI - The cancer problem in Poland: epidemiological trends, organization of specialized treatment, intervention programmes and research. PMID- 1743314 TI - Intravenous immunoglobulin treatment for recurrent abortions caused by antiphospholipid antibodies. AB - There is an association between the presence of antibodies that bind to anionic phospholipids and the occurrence of repeated spontaneous abortion. Many uncontrolled studies have reported favorable pregnancy outcome in women treated with steroids, low-dose aspirin, heparin, or their combination. Similarly, treatment failures have been reported with most of these therapeutic regimens. Immunoglobulins play a central role in immune regulation. A wide spectrum of human diseases are associated with decreased or abnormal regulation of Ig levels. Recently, IV preparations of Ig have become available for clinical use, including treatment of patients with recurrent abortions and high levels of antiphospholipid antibodies. The effectiveness of this new mode of therapy can be related to several immunological mechanisms such as blockade of antibody binding to receptors on macrophages, increase in T suppressor cells, or decrease in antibody synthesis. The latter effect may be mediated by anti-idiotypic antibodies in the Ig preparation. Determination of dosage of IV Ig, duration of treatment, and treatment intervals are all empirical in patients with recurrent abortions and high levels of antiphospholipid antibodies because antiphospholipid antibody levels are not useful for monitoring therapy. Although the data available at present are promising, additional randomized trials are needed to determine the efficacy of IV Ig in patients with immunological recurrent abortions. PMID- 1743315 TI - Partners in pursuit of excellence: development of an embryo laboratory accreditation program. PMID- 1743316 TI - Prevalence of human immunodeficiency virus in an infertile population. AB - OBJECTIVE: To assess the prevalence of human immunodeficiency virus (HIV) antibody in infertility. DESIGN: Prospective cross-sectional blind study. SETTING: An infertility clinic in Barcelona. PATIENTS: Three hundred thirty-five consecutive patients (308 infertile women and 27 spontaneous recurrent aborters) were seen between January 1989 and May 1990. MAIN OUTCOME MEASURE: Human immunodeficiency virus serostatus. RESULTS: The rate of seropositivity in the group of patients studied was 0.3% (95% confidence interval 0% to 0.9%). CONCLUSION: Further studies are desirable to establish the value of routine HIV testing in infertility patients as a population of women actively seeking pregnancy. PMID- 1743317 TI - Effects of vehicle supplementation on total estradiol absorption from a transdermal estradiol delivery system. AB - OBJECTIVE: To evaluate the effects of vehicle supplementation on serum estradiol (E2) delivery pharmacokinetics from the Ciba-Geigy (Summit, NJ) 0.1-mg Estraderm Patch. DESIGN: Postmenopausal women were randomized to a 28-day crossover treatment protocol separated by a 14-day wash out period. SETTING: Normal human volunteers were studied in an academic research environment. PATIENTS, PARTICIPANTS: The subject pool included eight healthy postmenopausal women between 32 and 60 years of age. INTERVENTIONS: In treatment A, a 0.1-mg Estraderm Patch was worn for 7 days; in treatment B, and identical patch was worn into which 0.6 mL of ethanol was injected on day 3 of use. MAIN OUTCOME MEASURES: Serum E2 levels were measured in both groups. RESULTS: Although E2 absorption showed characteristic interpatient variability, addition of ethanol significantly extended the mean time for serum E2 levels to return to baseline, without increasing peak absorption. The mean extension was 50 hours. CONCLUSION: The addition of ethanol to the Estraderm Patch increased the duration of elevated serum E2 levels measured in menopausal women, thus potentially increasing the effective life span of the transdermal therapeutic system. PMID- 1743318 TI - Comparative bioavailability of orally and vaginally administered progesterone. AB - OBJECTIVE: To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone. DESIGN: Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later. SETTING: The study was conducted in outpatient setting. SUBJECTS: All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it. INTERVENTIONS: Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg. MAIN OUTCOME MEASURE: Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability. RESULTS: Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA). CONCLUSIONS: The two formulations had similar bioavailability. PMID- 1743319 TI - Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea. AB - OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double blind. SETTING: Academic institution. PARTICIPANTS: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo. MAIN OUTCOME MEASURES: Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E2) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E2 and P concentrations. PMID- 1743320 TI - Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients. AB - OBJECTIVE: To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs. DESIGN: Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Nine patients with isolated hypogonadotropic hypogonadism. MAIN OUTCOME MEASURE: Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation. RESULTS: Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05). CONCLUSION: This study in isolated hypogonadotropic hypogonadism patients is consistent with the two cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question. PMID- 1743321 TI - Endocrinology of gonadotropin-releasing hormone induced cycles in hypothalamic amenorrhea: the role of the pulse dose. AB - OBJECTIVE: To find the treatment regimen giving a maximum chance of ovulation and a minimal chance of multiple follicular development in pulsatile gonadotropin releasing hormone (GnRH) therapy in patients with hypothalamic amenorrhea. DESIGN: We propectively studied the endocrinology of cycles induced with 5, 10, and 20 micrograms GnRH pulse doses, randomly assigned per patient, comparing this with the endocrinology of spontaneous menstrual cycles. SETTING: All patients were treated at the Academic Hospital of the Vrije Universiteit, Division of Reproductive Endocrinology and Fertility. PATIENTS: Fifteen patients with hypothalamic amenorrhea were treated for one to three cycles; 14 normally cycling volunteers were studied for one cycle. MAIN OUTCOME MEASURE: Number of ovulations per pulse dose; luteinizing hormone, follicle-stimulating hormone, total urinary estrogens (Es), and pregnanediol were measured per cycle day and per stimulation day. RESULTS: The endocrinology of all ovulatory cycles remained within the normal range. First treatment cycles showed significantly higher ovulation rates compared with subsequent cycles. Significantly more anovulation was observed in cycles with 5-micrograms pulse doses. Luteal Es were significantly higher in induction cycles compared with controls. CONCLUSIONS: The optimum treatment regimen should be to start induction with 5 micrograms/pulse in the first cycle and to raise the dose to 10 micrograms/pulse in subsequent cycles, regardless of the outcome of the first cycle. After ovulation, the pulse interval should be changed to 240 minutes. PMID- 1743322 TI - Transvaginal ultrasound-guided follicular aspiration in the management of anovulatory infertility associated with polycystic ovaries. AB - STUDY OBJECTIVE: To investigate whether or not transvaginal ultrasound (US) guided follicular aspiration can effectively induce ovulation and facilitate pregnancy in anovulatory patients with polycystic ovaries (PCO). DESIGN: Eight patients with polycystic ovarian disease (PCOD) and 10 patients with PCO were participants who failed to ovulate by the medical therapies. Most of persistent follicles were punctured, and their contents were thoroughly aspirated during the midluteal phase. The same ovarian stimulation regimen as used in the previous cycles were administered in the cycles after the aspiration. MAIN OUTCOME MEASURES: Evidence of ovulation and a subsequent pregnancy was ultrasonically monitored after the aspiration, and the responsiveness of pituitary gonadotropins to gonadotropin-releasing hormone was tested in these patients. RESULTS: The ovulation rates were 87.5% per patient, 52.6% per cycle monitored in PCOD patients and 100% per patient, 63.3% per cycle monitored in PCO patients, respectively. Half of the patients both with PCOD and PCO achieved pregnancy after the aspiration. A significant decrease (P less than 0.05) of the basal and peak levels of serum luteinizing hormone was observed after the aspiration. CONCLUSIONS: The US-guided follicular aspiration seems to be a new surgical method for treating anovulatory patients with PCO. PMID- 1743323 TI - Elimination of ovulation and menstrual cyclicity (with danazol) improves dysphoric premenstrual syndromes. AB - OBJECTIVE: To assess whether the therapeutic effect of danazol on premenstrual syndromes (PMS) is associated with suppression of ovulation. DESIGN: After 1 month on placebo, we administered 200 mg/d of danazol for 90 days to 24 women with dysphoric PMS. Symptoms during ovulatory cycles were compared with anovulatory periods. SETTING: Outpatient PMS program in a general hospital. PATIENTS: Twenty-four women who had dysphoric PMS and otherwise were physically and mentally healthy. INTERVENTIONS: None (except the oral medication). MAIN OUTCOME MEASURE: Prospective daily monitoring of symptoms with the Daily Rating Form, before, during, and after treatment. RESULTS: Twenty of 23 anovulatory periods were symptom-free versus 6 of 32 ovulatory periods (chi 2 = 15.63, P = 0.0002). CONCLUSION: The beneficial effect of danazol as treatment depends mostly on achieving an an-ovulatory state and elimination of hormonal cyclicity and not on the drug per se. PMID- 1743324 TI - Local luteolytic effect of prostaglandin F2 alpha in the human corpus luteum. AB - OBJECTIVE: To evaluate the effects of prostaglandin (PG)F2 alpha on human corpus luteum (CL) function in vivo. DESIGN: The effects of a single injection of PGF2 alpha into the CL was studied. SETTING: The patients underwent elective surgery at the Department of Obstetrics and Gynecology, Sahlgrenska Hospital, University of Goteborg, Sweden. PARTICIPANTS: Twenty women with regular menstrual cycles undergoing laparoscopy for legal sterilization with tubal clips volunteered for the study. INTERVENTIONS: Prostaglandin F2 alpha (3 mg) was injected through the abdominal wall into the CL. In control cases, vehicle was injected into the CL or PGF2 alpha into the contralateral ovary. MAIN OUTCOME MEASURE: After the injections, serum was analyzed for progesterone (P) and luteinizing hormone using fluoroimmunoassay and enzyme-immunoassay, respectively. Menstrual data were recorded. RESULTS: In contrast to control cases, intraluteal injection of PGF2 alpha caused both an immediate fall of greater than 30% in serum P and a shortening of the luteal phase by 2 to 5 days. Luteinizing hormone varied independently of the changes in serum P levels. CONCLUSION: The results suggest a local role for PGF2 alpha in human luteolysis. PMID- 1743325 TI - Severe ovarian hyperstimulation syndrome: role of peripheral vasodilation. AB - OBJECTIVE: To investigate the pathogenesis of the systemic hemodynamic disturbance and the renal production of vasodilator prostaglandins (PGs) in the ovarian hyperstimulation syndrome. DESIGN: Prospective longitudinal study. SETTING: Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona. PATIENTS: Five in vitro fertilization patients with ascites because of severe ovarian hyperstimulation syndrome. MAIN OUTCOME MEASURES: Measurement during the syndrome and 4 weeks after recovery of the following: cardiac output, arterial pressure, estimated peripheral vascular resistances, hematocrit, standard renal function tests, plasma renin activity, plasma aldosterone, norepinephrine and antidiuretic hormone concentrations, and urinary excretion of PGE2 and 6-keto-PGF1 alpha. RESULTS: During the syndrome, all patients showed arterial hypotension (74.2 +/- 3.8 versus 85.8 +/- 1.0 mm Hg), tachycardia, increased cardiac output (6.4 +/- 0.2 versus 4.4 +/- 0.1 L/min), low peripheral vascular resistance (929 +/- 52 versus 1,568 +/- 51 dyn/sec per cm-5), high plasma levels of renin (72 +/- 25 versus 0.5 +/- 0.1 ng/mL per h-1), norepinephrine (639 +/- 141 versus 203 +/- 21 pg/mL) and antidiuretic hormone (6.1 +/- 1.6 versus 1.5 +/- 0.1 pg/mL), and increased urinary excretion of PGE2 (551 +/- 152 versus 106 +/- 44 pg/min) and 6-keto-PGF1 alpha (470 +/- 76 versus 99 +/- 11 pg/min). No evidence of hemoconcentration, as assessed by hematocrit, was observed in any patient. CONCLUSIONS: (1) Severe ovarian hyperstimulation syndrome is related to marked arteriolar vasodilation that leads to underfilling of the arterial vascular compartment and stimulation of endogenous vasoconstrictor systems and (2) the increased urinary excretion of PGs probably represents a homeostatic response to antagonize the renal effects of these systems. PMID- 1743326 TI - Are consumers of modern fertility treatments satisfied? AB - OBJECTIVE: To determine the extent of patients satisfaction with fertility treatments, its antecedents, and its correlates. DESIGN: This is a two-wave correlational panel study in which consumer satisfaction was assessed 6 and 12 months after admission to the clinic. PATIENTS: The sample consisted of 385 couples who consulted the fertility clinic of a large metropolitan hospital. MEASURES: After their admission, patients completed scales measuring psychosocial disturbances. These variables were reassessed 6 and 12 months later along with a consumer satisfaction questionnaire. RESULTS: Patients were generally satisfied with modern fertility treatments. Approximately 10% of the sample expressed dissatisfaction with received services. Analyses revealed that consumer satisfaction was significantly related to poor psychosocial functioning at intake and after 6 months. CONCLUSIONS: Our results suggest that consumers of fertility treatments are generally satisfied with the quality and quantity of service they received at the clinic. The more patients exhibited personal, marital, and social symptoms of distress when they were admitted to the clinic, the more they were likely to be later dissatisfied with fertility treatments. PMID- 1743327 TI - Aging of endometrium and oocytes: observations on conception and abortion rates in an egg donation model. AB - OBJECTIVE: To assess the comparative contribution of endometrial and oocytic aging to the decline in fertility with age. DESIGN: Retrospective analysis of conception and abortion rates in an egg donation program, with respect to donor and recipient ages. PATIENTS: All oocyte recipients had ovarian failure. Donors were women undergoing in vitro fertilization who contributed up to a third of retrieved oocytes. INTERVENTIONS: None. RESULTS: Thirty pregnancies (28 intrauterine) were recorded in 169 reception cycles originating from 91 donation cycles. Women who conceived were younger than those who did not (median age 31 versus 37; P less than 0.046), with no difference in age of donors. There was a significant difference in spontaneous abortion rate by age of donor rather than by age of recipient. Donors to successful pregnancies were younger than donors to aborted pregnancies (median age 27.5 versus 33; P less than 0.0211), but the 11 women with aborted pregnancies did not differ in age from the 17 women with successful pregnancies. CONCLUSIONS: In women, endometrial function as expressed by conception rate in the recipients declines with age, whereas it is oocyte age that primarily influences risk of abortion. PMID- 1743328 TI - The effect of pituitary suppression and the women's age on embryo viability and uterine receptivity. AB - OBJECTIVE: To examine the effect of pituitary suppression and the women's age on embryo viability and uterine receptivity. DESIGN: Retrospective analysis of 394 embryo transfers (ET) after in vitro fertilization (IVF). SETTING: Community hospital IVF program from 1986 to 1990. PATIENTS: Three groups were studied: women less than 40 years with pituitary suppression (group 1) and without pituitary suppression (group 2); women 40 years of age and older with pituitary suppression (group 3). INTERVENTIONS: Pituitary suppression was achieved in groups 1 and 3 with daily leuprolide acetate starting in the luteal phase; human menopausal gonadotropin and progesterone were given intramuscularly. MAIN OUTCOME MEASURES: Ongoing and multiple ongoing pregnancy rates (PRs) were compared in the three groups. A mathematical model of implantation was used to estimate embryo viability and uterine receptivity. RESULTS: Ongoing and multiple ongoing PRs per ET in group 1 (28.6% and 12.3%) were significantly higher than the corresponding rates in group 2 (16.9% and 2.4%) and in group 3 (16.9% and 3.4%). Implantation analysis revealed higher embryo viability without change in uterine receptivity with pituitary suppression (group 1 versus 2). Decrease in both embryo viability and uterine receptivity was noted in women greater than 40 (group 1 versus 3). CONCLUSIONS: (1) Pituitary suppression improved implantation outcome by increasing embryo viability with no change in uterine receptivity and was associated with a high multiple PR in women less than 40; (2) in women greater than 40 both embryo viability and, to a lesser extent, uterine receptivity were decreased; (3) transfer of a larger number of embryos in older patients may improve IVF outcome without excessive risk of multiple pregnancy. PMID- 1743329 TI - Cotreatment with growth hormone, after pituitary suppression, for ovarian stimulation in in vitro fertilization: a randomized, double-blind, placebo control trial. AB - OBJECTIVE: To explore the effect of cotreatment with growth hormone (GH) for ovarian stimulation after pituitary suppression. DESIGN: A randomized, double blind, placebo-controlled study. SETTING: Specialist Reproductive Endocrine and In Vitro Fertilization (IVF) Unit. PATIENTS, PARTICIPANTS: Twenty-five IVF patients who had responded suboptimally in a previous treatment cycle. A subgroup of 18 patients were found to have ultrasound (US) findings of polycystic ovaries (PCO). MAIN OUTCOME MEASURE: The amount of gonadotropin used, development of follicles greater than or equal to 14 mm, number of oocytes collected, fertilized, cleaved and replaced, serum and follicular fluid (FF) insulin-like growth factor I (IGF-I) concentrations. RESULTS: Cotreatment with GH was associated with a significant reduction in gonadotropins requirement (P less than 0.05). In patients with US-diagnosed PCO more follicles developed (P less than 0.05), more oocytes were collected (P less than 0.03), fertilized (P less than 0.004), and cleaved (P less than 0.02). A significantly higher FF IGF-I concentrations were found in patients receiving cotreatment with GH compared with those who received placebo (P less than 0.04). CONCLUSION: We believe that there may be a place for GH treatment in selected IVF cycles after pituitary suppression but what the role of IGF-I should further be investigated. PMID- 1743330 TI - Poor implantation of cryopreserved reinsemination-fertilized human embryos. AB - OBJECTIVE: To investigate whether a poor rate of implantation after in vitro fertilization (IVF) was due to poor embryonic/endometrial synchrony during the original IVF cycle, we have cryopreserved reinseminated-fertilized embryos for later more synchronous replacement after thawing. The chance of implantation of fresh reinseminated fertilized human oocytes is approximately one tenth that of timely fertilized embryos. STUDY DESIGN AND DATA: Retrospective study of 35 original oocyte collections in which initial normal fertilization was 47.3% (129/273 oocytes), with 49.6% fertilization (67/135) upon reinsemination. Of these, 70 initially fertilized and 67 reinsemination-fertilized embryos were cryopreserved, and 50 initially fertilized and all 67 reinsemination-fertilized embryos were subsequently thawed with 72% and 63% cryosurvival, respectively, (not significant). SETTING: Private infertility clinic. RESULTS: In 11 cycles, 23 thawed initially fertilized embryos (group A) were replaced with a 21.7% implantation rate per embryo; in 10 cycles, 13 initially fertilized and 12 reinsemination-fertilized embryos (group B) were replaced together with an 8% implantation rate; finally, in 16 cycles, 30 reinsemination-fertilized embryos (group C) were replaced with a 3.3% implantation rate (group A versus group C: P = 0.076). Comparison of clinical pregnancies between these groups was significantly different (6/11 versus 1/16; P = 0.0427). CONCLUSION: Reinsemination-fertilized embryos survive freezing as well as initially fertilized embryos, but better embryonic/endometrial synchrony does not improve chances of their implantation. PMID- 1743331 TI - Microinjection of human oocytes: a technique for severe oligoasthenoteratozoospermia. AB - OBJECTIVE: To determine outcome after microinjection with very poor quality sperm and after failed fertilization. DESIGN: Group 1, fresh oocytes from patients with very low sperm density and motility on the day of oocyte recovery; Group 2, 1-day old oocytes that failed to fertilize. SETTING: All material was obtained from the National University Hospital. PATIENTS: One hundred and thirty-one from group 1; 35 from group 2. INTERVENTIONS: Sperm was injected subzonally or directly into the ooplasm. MAIN OUTCOME MEASURE: Normal and abnormal fertilization and pregnancy. RESULTS: Subzonal transfer was done on 771 oocytes in group 1 and 188 oocytes in group 2. Multiple sperm were transferred [mean of 6.6 for group 1 and 7.3 for group 2]. Monospermic fertilization occurred in 16.6% and 14.9%, respectively. Polyspermy and parthenogenetic activation were low at 2.3% and 2.8%, respectively. Five pregnancies were obtained, but only one delivered. Ooplasmic injection (single sperm heads) was done in 38 oocytes from three patients with extremely severe oligozoospermia; only four two-pronuclear zygotes were obtained and replaced into two patients, without any resulting pregnancy. CONCLUSIONS: Subzonal transfer may be a viable technique for patients with severe sperm problems. PMID- 1743332 TI - Assessment of the relevance of zona pellucida antibodies in serum and cervical mucus in patients who have fertilization failure during in vitro fertilization. AB - OBJECTIVE: To assess whether antibodies to the zona pellucida can cause fertilization failure during in vitro fertilization (IVF). DESIGN: Two methods for detecting zona pellucida antibodies were used to assess 20 women undergoing IVF. Nine patients had failed fertilization during the treatment cycle. SETTING: Academic IVF department of a teaching hospital. PATIENTS: Infertile patients previously assessed as requiring IVF. INTERVENTIONS: Gonadotropin-releasing hormone analogue to achieve pituitary down regulation and human menopausal gonadotropin for superovulation. Transvaginal ultrasound directed oocyte recovery. Cervical mucus and serum samples were obtained. MAIN OUTCOME MEASURES: The presence of antizona pellucida antibodies in serum or cervical mucus in relation to fertilization. RESULTS: Seven of 20 patients had antizona antibodies in serum and 7 of 20 patients had antibodies in mucus. Only 1 patient had antibodies in both samples. No correlation between the presence of antibodies in either sample and failure of fertilization was found. CONCLUSION: Detection of antizona pellucida antibodies by the methods described have no role in the prediction of IVF. PMID- 1743333 TI - Movement characteristics of human epididymal sperm used for fertilization of human oocytes in vitro. AB - STUDY OBJECTIVE: To develop mathematical models using kinematic parameters from Computer-Aided Sperm Analysis (CASA) that predict the fertilization rate of sperm recovered from the caput epididymidis and to test the hypothesis that fertilization was enhanced by the presence of specific sperm subpopulations in the inseminate. SETTING: In vitro fertilization (IVF) program. PATIENTS: Thirteen patients with congenital absence of the vas deferens provided epididymal sperm for IVF as well as for CASA. RESULTS: The mathematical model that was most predictive of fertilization rates included kinematic parameters of the epididymal aspirate (percent motility), the inseminate used for IVF (curvilinear velocity [VCL]), and the change in sperm movement after in vitro processing by the mini Percoll technique (difference in amplitude of lateral head displacement [ALH]). Multivariate cluster analysis revealed that inseminates that resulted in higher fertilization rates had subpopulations of sperm that were characterized by high VCL and high mean angular displacement, as well as a greater change in ALH after processing. CONCLUSION: In vitro fertilization with epididymal sperm was more likely to succeed when the sperm population that was initially aspirated had a higher proportion of motile cells and when these sperm were capable of capacitation in vitro as indicated by the appearance of sperm subpopulations with motility that resembled hyperactivation. PMID- 1743334 TI - 31P magnetic resonance spectroscopy for diagnosing abnormal testicular function. AB - OBJECTIVE: To determine if testicular 31P magnetic resonance (MR) spectroscopy can be of additional clinical value. DESIGN: A controlled study in three selected subjects groups. SETTING: All participants were referred to the outpatient clinic of our Department of Obstetrics and Gynecology. PARTICIPANTS: Normal healthy volunteers (n = 13), oligozoospermic (n = 14), and azoospermic patients (n = 17; 6 with epididymal obstruction and 11 with severe germ cell depletion) were selected on the basis of semen analysis, hormone determinations, and, if necessary, on operative exploration. INTERVENTIONS: Magnetic resonance spectroscopy was performed on a Philips Gyroscan S15 (Philips Medical Systems, Best, the Netherlands). MAIN OUTCOME MEASURE(S): The routine clinical analyses were compared with the outcome of testicular MR spectroscopy to test the hypothesis that MR spectroscopy can be of additional value in the diagnosis of idiopathic oligozoospermic or azoospermic patients. RESULTS: The MR spectra of normal volunteers were significantly different from oligozoospermic patients (P less than 0.001), from azoospermic patients with germ cell depletion (P less than 0.001), and from azoospermic patients with an obstruction (P less than 0.05). Between the two azoospermic groups also a significant difference was found (P less than 0.001). CONCLUSIONS: These results show that MR spectroscopy is a reliable technique to monitor the testicular function. PMID- 1743335 TI - Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. AB - OBJECTIVE: To compare pulsatile gonadotropin-releasing hormone (GnRH) therapy with gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. DESIGN: Prospective study. Patients had free choice between the two forms of therapy. SETTING: Patients were treated on an outpatient basis in our department. PATIENTS: Eighteen patients of matched age (mean [+/- SD] age: 21.1 +/- 3.0 years and 23.6 +/- 7.3 years) and similar testicular volume were treated in each group. INTERVENTIONS: Pulsatile GnRH therapy was started with 4 micrograms GnRH subcutaneously every 2 hours using a portable pump and gonadotropin therapy with 3 x 2,500 IU human chorionic gonadotropin (hCG) weekly injected intramuscularly. After 8 to 12 weeks of hCG treatment, 150 IU human menopausal gonadotropin two to four times weekly were added. RESULTS: Testosterone (T) and estradiol (E2) levels increased significantly higher (T: P less than 0.03; E2; P less than 0.001) in the gonadotropin group than in the GnRH group (T: 22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/L; E2: 150 +/- 70 versus 88. +/- 59 pmol/L). Five patients developed gynecomastia during gonadotropin therapy. The rise of testicular volume was significantly more pronounced (P less than 0.001) in the GnRH group (delta testicular volume = 8.1 +/- 2.0 mL) than in the gonadotropin group (delta testicular volume = 4.8 +/- 1.8 mL). Ten patients of the GnRH and 8 of the gonadotropin group had positive sperm counts, ranging from 1.5 to 26 x 10(6) spermatozoa/mL. The latter was achieved more rapidly in the GnRH group (12 +/- 1.6 versus 20 +/- 2.3 months: P less than 0.02). CONCLUSIONS: Endocrine and exocrine testicular function can be normalized by both forms of therapy. Gonadotropin therapy has more side effects. Gonadotropin-releasing hormone leads to a higher testicular volume and a more rapid initiation of spermatogenesis compared with gonadotropin therapy. PMID- 1743336 TI - Cryopreservation of the occasionally improved semen samples for intrauterine insemination: a new approach in the treatment of idiopathic male infertility. AB - OBJECTIVE: To assess the value of treating idiopathic male infertility by intrauterine insemination (IUI) of the occasionally improved cryopreserved semen. DESIGN: Two groups of idiopathic oligospermic patients were chosen at random and treated by IUI using processed fresh semen in group A and the best available cryopreserved semen samples pooled with fresh samples in group B. SETTING: Egyptian IVF-ET Centre, Maadi, CAiro, Egypt. PATIENTS, PARTICIPANTS: One hundred fifty infertile couples because of idiopathic oligoasthenospermia. INTERVENTION: Intrauterine insemination. MAIN OUTCOME MEASURE: The pregnancy rate was evaluated after an average of three treatment cycles. RESULTS: The pregnancy rate (PR) was significantly higher in group B when compared with group A. The improvement in the PR was highly significant in the subgroup of patients for whom reasonable semen samples could be collected and cryopreserved. CONCLUSIONS: Our study indicates that IUI with fresh semen pooled with cryopreserved occasionally improved semen samples for the treatment of oligoasthenospermia results in an improved PR. PMID- 1743337 TI - Defining the valid hemizona assay: accounting for binding variability within zonae pellucidae and within semen samples from fertile males. AB - OBJECTIVE: To achieve a better understanding of the variability in sperm and oocyte binding capacities will optimize use of the hemizona assay (HZA) as a predictor of sperm function. DESIGN: Limitations of the HZA were more clearly delineated by current studies: (1) variability of sperm binding capacity of men over a 90-day interval; (2) variability of sperm binding using different oocytes; and (3) lower limits of the number of sperm bound from the fertile control in two laboratories. PATIENTS: Semen was obtained from proven fertile men and one subfertile individual. MAIN OUTCOME MEASURE: The number of sperm tightly bound to the hemizona were measured and compared. RESULTS: In the initial study, 6 fertile control men exhibited a similar degree of variability in zona binding when studied over a 90-day interval. Average sperm binding for individuals ranged from 68 to 127. Second, 3 of the 15 simultaneous assays showed very low numbers of sperm bound, indicating that 20% of the zonae had poor binding. Third, from 18 men who had 0% fertilization in an in vitro fertilization system using mature oocytes, evaluation of their sperm by HZA was performed. The sperm bound poorly and the 95% confidence interval was 20 sperm bound. Thus, the fertile controls should bind greater than 20 sperm to distinguish them from the infertile group in the HZA system resulting in a valid assay. CONCLUSIONS: With these guidelines, applications of the HZA may be made with greater reassurance of a valid bioassay of sperm fertilizing potential. PMID- 1743338 TI - Filtration of spermatozoa through L4 membrane: a new method. AB - OBJECTIVE: To explore the possibility of using the L4 membrane filtration device for processing of spermatozoa for intrauterine insemination and other assisted reproductive techniques. DESIGN, SETTING, PATIENTS: Semen samples from 15 patients attending an infertility clinic of a tertiary referral institution and from seven fertile donors were used for the study. MAIN OUTCOME MEASURES: The effect of L4 membrane filtration was studied on the following semen parameters: sperm motility, velocity, percentage of normal and abnormal sperm forms, and percentage and concentration of round cells in semen. RESULTS: The statistical analysis of data from both the subfertile patient population and the normal fertile donor group showed similar improvement in semen quality after L4 membrane filtration. Therefore, the results for these two groups were combined for statistical purposes. Our findings demonstrate a significant increase in normal sperm forms and a decrease in abnormal forms after filtration of specimens through the L4 membrane. In all subjects, the mean sperm motility increased from 47% to 77% (P less than 0.0001); velocity increased from 30 to 48 microns/seconds (P less than 0.0001); normal sperm forms increased from 53% to 84% (P less than 0.0001); abnormal forms decreased from 28% to 10% (head defects) (P less than 0.0001); neck defects from 3.5% to 1% (P less than 0.0006); tail defects from 8% to 3.5% (P less than 0.005); and undifferentiated round cells decreased from 6% to less than 1% (P less than 0.002) after filtration. The concentration of round cells counted by the Makler chamber (Sefi Medical, Haifa, Israel) decreased significantly from 6 x 10(6)/mL to 0.2 x 10(6)/mL (P less than 0.0003). Similarly, white blood cell counts measured by the Endtz test also decreased from 3.4 x 10(6)/mL to less than 0.1 x 10(6) (P less than 0.043). CONCLUSION: We conclude that the filtration of the semen specimens through L4 membrane results in a significant improvement in semen parameters and should be considered as an adjunct in sperm processing. PMID- 1743339 TI - Pregnancy after fimbriectomy reversal: results of microsurgery augmented by gamete intrafallopian tube transfer and embryo transfer. AB - In this study, fimbriectomy reversal resulted in a 43% intrauterine PR and a fecundability of 6.6%. The cumulative PR and the fecundability were 57% and 7.8%, respectively, when microsurgery was augmented by GIFT and embryo cryopreservation during the same treatment cycle and by subsequent embryo thaw and transfer. PMID- 1743340 TI - A novel superovulation regimen: three-day gonadotropin-releasing hormone agonist with overlapping gonadotropins. PMID- 1743341 TI - Influence of endometrial thickness and echo patterns on pregnancy rates during in vitro fertilization. AB - Previous data has suggested that improved PRs were seen in women with increased endometrial thickness as determined by sonography before oocyte retrieval. The hyperstimulation protocol used was CC-hMG. The study presented herein was initiated to evaluate if a similar trend was evident in women whose hyperstimulation protocol included the long LA-hMG therapy. We also demonstrated an improved PR in women with greater endometrial thickness, but in general, the endometrium was thicker in the pregnant women treated with the gonadotropin releasing hormone agonist than in those treated with CC. PMID- 1743342 TI - A comparison of intrauterine insemination, intraperitoneal insemination, and natural intercourse in superovulated women. AB - In a prospective comparison of IP, IUI, and natural intercourse following superovulation in couples diagnosed as having unexplained infertility, semen factors, or sperm antibodies, pregnancy rates were found to be significantly higher after IP. Pregnancy rates were also higher in the unexplained infertility group when compared with those with semen factors. It was concluded that IP in combination with superovulation offered a simple, inexpensive, safe alternative to GIFT. PMID- 1743343 TI - Anaphylaxis during intrauterine insemination secondary to bovine serum albumin. AB - A case of anaphylaxis is reported after IUI with sperm processed in Tyrode's solution supplemented with BSA. The patient had a positive prick cutaneous test to BSA and also had specific IgE antibody against it. Repeat IUI using the patient's own blood serum instead of BSA for processing the sperm proceeded without incident. Clinicians should be aware of this rare, but not inconsequential, adverse effect of using xenogeneic proteins during IUI and other assisted reproductive techniques. PMID- 1743344 TI - Mullerian defects in women with normal reproductive outcome. AB - The incidence of uterine congenital anomalies because of mullerian defects in the normal fertile population is 3.2% (22/679). Twenty (90%) of them are septate uteri, whereas a bicornuate (5%) and a didelphys uterus (5%) have been also found in this population. Based on these findings, we question the usefulness of the septum resection in patients with septate uterus and no previous reproductive failure. PMID- 1743345 TI - Term pregnancy after fallopian tube transposition. AB - A 23-year-old woman suffered from primary sterility because of congenital malformation of the uterus and tubes. There was a left unicornuate uterus. The left ovary and the isthmic and ampullary parts of the right tube were missing. Microsurgical transposition of the left tube was performed successfully. Our technique may encourage microsurgeons to use transposition of fallopian tube in cases in which only one tube and one ovary on contralateral sides are available. PMID- 1743346 TI - Treatment of unruptured tubal pregnancy by local injection of methotrexate and prostaglandin F2 alpha in 52 patients. AB - Uncomplicated tubal pregnancies were treated by local injection of methotrexate (25 to 50 mg) and PGF2 alpha (5 to 10 mg). Trophoblastic resorption occurred in 50 (96.1%) of 52 patients within 20 days after treatment and without side effects. Three months after treatment, the affected tube was patent in 43 (91.4%) of 47 patients continuing in the study, and the subsequent intrauterine pregnancy rate was 40.4%. The combined use of methotrexate and PGF2 alpha appears to be a promising treatment for tubal pregnancy and should be evaluated further. PMID- 1743347 TI - Reliability of the visual diagnosis of ovarian endometriosis. AB - The visual diagnosis of endometrioma at laparotomy in 245 women operated on for ovarian cysts demonstrated a sensitivity of 97%, specificity of 95%, positive and negative predictive value of 98% and 94%, respectively, and overall accuracy of 96%. Because the visual detection of endometriomas is remarkably accurate, ovarian biopsy, although desirable in some cases, would seem dispensable for a correct laparoscopic diagnosis and staging of the disease. PMID- 1743348 TI - Penetration of zona-free hamster oocytes by ejaculated cryopreserved gorilla spermatozoa. AB - Semen obtained by electroejaculation from two lowland gorillas were cryopreserved in TEST yolk to evaluate the ability of spermatozoa to penetrate zona-free hamster oocytes. Thawed semen was processed through a two-layer Percoll density gradient to obtain motile spermatozoa for the SPA. The processed sperm penetrated greater than 25% of the zona-free hamster oocytes. Thus, the use of TEST yolk to cryopreserve gorilla semen and processing the thawed semen through Percoll gradient to concentrate motile spermatozoa may facilitate sperm capacitation and the ability to penetrate oocytes. PMID- 1743349 TI - A critical look at hCG "doubling time". PMID- 1743350 TI - Genetic source of femininity. PMID- 1743351 TI - Myco-contamination of incubators used for human pre-embryo culture. PMID- 1743352 TI - Antisperm antibodies in serum and genital tract secretions. PMID- 1743353 TI - Complications of 5--fluorouracil after trabeculectomy. AB - Trabeculectomy has a very high success rate, however, certain eyes are known to be at high risk of failure due to scarring of the conjunctival bleb. Such eyes include those with a previous failed filter, eyes with glaucoma secondary to uveitis and neovascularisation and the eyes of children and young adults. Trabeculectomy is generally accepted to have less successful results in patients of African race although good results are reported from some centres. The effectiveness of treatment with 5-fluorouracil in improving the results of trabeculectomy has been established in a number of pilot studies and clinical trials. Early studies used 100 mg of 5-fluorouracil in divided doses. Serious complications were recorded and lower dose regimes have been advised to improve the safety of the technique. Similar success in improving the chance of success to trabeculectomy has been found with doses of 40 mg with a lower incidence of side effects. We report complications associated with the use of 5-fluorouracil in a total dose of 50 mg in a group of 49 eyes undergoing trabeculectomy and postoperative 5-fluorouracil and describe the previously unreported increased incidence of thin cystic blebs in these eyes. PMID- 1743354 TI - Pilocarpine to prevent acute pressure increase following primary laser trabeculoplasty. AB - The effect of pilocarpine pretreatment on the transient pressure elevations immediately following primary laser trabeculoplasty was investigated in a prospective, randomised study. Fifty eyes of 50 patients, 33 with exfoliative and 17 with simple glaucoma, were treated in 360 degrees of the trabecular meshwork. The mean maximum pressure increase was 2.4 (SD = 4.4)mm Hg with pilocarpine pretreatment and 12.8 (SD = 11.2)mm Hg without pretreatment (p less than 0.05). Except in two cases, all peak pressures appeared during the first two hours after treatment. The degree of chamber angle pigmentation was predictive of the magnitude of the post laser hypertensive pressure response in eyes without pretreatment (p less than 0.05). PMID- 1743355 TI - Meibomian gland disease. Classification and grading of lid changes. AB - In recent years attention has been paid to meibomian gland dysfunction (MGD) as a distinct clinical entity responsible for chronic symptoms and signs and occurring independently or in association with atopy, cicatrising mucosal disorders and rosacea. Attempts to correlate MGD with microbiological and lipid biochemical changes are confounded by the absence of a clear descriptive language for the disorder and its associated changes. Such a language is crucial for the conduct of cross-sectional and natural history studies and therapeutic clinical trials. We present a comprehensive classification and grading scheme of meibomian gland disease, supporting our observations with illustrations. PMID- 1743356 TI - Is raised intraocular pressure a bad prognostic sign in acute corneal graft rejection? AB - One hundred and forty acute corneal rejection episodes in 94 patients were studied retrospectively. Sixteen episodes in 15 eyes were associated with raised intraocular pressure (IOP) on admission, three of whom had had previously elevated IOP. At six weeks, six (37.5%) still required hypotensive therapy. Five eyes with raised IOP at rejection had lost vision at six weeks. Five of the six eyes with graft failure at review had raised IOP either pre-graft, at rejection or at follow-up. Eyes grafted for herpes simplex keratitis with hypertensive rejection episodes had a higher mean admission IOP, with a more short-lived rise than other eyes. PMID- 1743357 TI - The use of a single pulse of intravenous methylprednisolone in the treatment of corneal graft rejection. A preliminary report. AB - In corneal graft rejection, rapid reversal of the rejection process is necessary to minimise endothelial cell loss. Ten consecutive patients with acute endothelial rejection were treated with a single 500 mg pulse of methylprednisolone intravenously and topical prednisolone 1% drops hourly. The rejection episode was successfully reversed in eight (80%) of the 10 grafts. This preliminary trial indicates that cortico-steroid pulse therapy may be beneficial in the management of severe corneal graft rejection with the advantage of avoiding prolonged oral corticosteroid therapy. PMID- 1743358 TI - The role of penetrating keratoplasty in the management of microbial keratitis. AB - Penetrating keratoplasty was performed as an emergency procedure in 52 eyes which had perforated from acute microbial keratitis and in a further 11 where perforation had not yet occurred. The results are compared with those of keratoplasty in 33 non-infected perforations and 20 eyes where there had been microbial keratitis which had responded to medical therapy leaving a scarred cornea. This latter group had both a better five year survival (90%) compared to all the others (51%), p less than 0.05, and achieved significantly better visual acuities, p less than 0.005. PMID- 1743359 TI - Vascular changes in the posterior segment in clinical and experimental ocular inflammatory disease. AB - Posterior segment inflammatory disease can have several different effects on the retinal vasculature, all of which have potentially sight threatening consequences. Blood-retinal barrier breakdown is a common feature of the disease process with resulting retinal and macula oedema. Very little is known about the mechanism of this breakdown and in particular whether it is at the endothelial cell membrane or at the tight junctions between the endothelial cells--a matter of importance if better therapeutic regimes are to be devised in the future. This paper looks at this question in two animal models of posterior uveitis using different techniques. PMID- 1743360 TI - Binocular diplopia in unilateral aphakia: the role of botulinum toxin. AB - We have treated 12 unilaterally aphakic patients, with a manifest squint and binocular diplopia, with botulinum toxin injection to the appropriate horizontal rectus muscle, in an attempt to reduce the angle of squint and thereby resolve the diplopia. In all cases a short-term reduction in the angle of squint was achieved. In nine patients, whose aphakia was corrected with a contact lens, and eight of whom had had their lenses removed because of trauma, this reduction was only temporary. In three patients, however, who had had a non-traumatic cataract removed, replaced with a posterior chamber implant, control of the deviation was maintained long after the acute effect of the toxin had disappeared, with the development of coarse binocular single vision, a fusion range, and abolition of all diplopia. The possible reasons for these different responses are discussed and it is suggested that in cases of binocular diplopia following lens extraction, botulinum toxin treatment should be considered prior to any extraocular muscle surgery, as temporary reduction of the deviation may be sufficient to allow recovery of binocular single vision. PMID- 1743361 TI - Treatment of strabismus after retinal detachment surgery with botulinum neurotoxin A. AB - Thirty-one consecutive patients were treated with injections of Botulinum Neurotoxin A to rectus muscles for strabismus following retinal detachment surgery. In 14 cases the presenting problem was diplopia and in 17 cases the presenting problem was cosmetic appearance. A total of 67 injections was given. Twenty-seven cases had nine months or more follow-up. Of these, four of 11 cases with diplopia had fusion restored, four were shown to have no fusion potential, and three had temporary improvement only. In 16 cases with a primary cosmetic problem there was no useful effect in two, three had surgery as an alternative, three were realigned long-term, and eight had continuing maintenance therapy with toxin. Over half the series had undergone multiple detachment surgery, often for giant tears and other complex pathology. PMID- 1743362 TI - Three wall orbital decompression for Graves' ophthalmopathy via a coronal approach. AB - Ten patients with dysthyroid eye disease who underwent a three wall orbital decompression procedure performed via a coronal approach were reviewed. The indications, results, complications and surgical techniques involved in this surgery are discussed. We believe that this approach offers a number of advantages over other techniques and has a role in the management of carefully selected patients with dysthyroid eye disease who have severe unilateral or bilateral proptosis, with or without dysthyroid optic neuropathy. PMID- 1743363 TI - The oval pupil. AB - The dynamics of pupillary dilation induced by Phenylephrine 10% and Cyclopentolate 1% have been examined by flash photography. A correlation between anterior chamber depth and the pupil shape on dilation with Phenylephrine Hydrochloride 10% is described. It is postulated that these pupillary dilation dynamics support a sympathetic abnormality as a trigger for acute primary angle closure glaucoma. PMID- 1743364 TI - The systemic and genetic significance of congenital optic disc anomalies. AB - Optic disc anomalies have great significance as a clue to associated systemic problems and as a marker of inherited disease. Optic nerve hypoplasia and colobomas of the optic disc are the main visually significant disorders; however, the Morning Glory disc anomaly and Aicardi's syndrome may also be associated with visual impairment. PMID- 1743365 TI - Clearing the cataract backlog in a (not so) developing country. AB - There is a significant backlog of patients waiting for cataract operations in the United Kingdom. In England in the first quarter of 1989, there were 74,000 patients in total on ophthalmology waiting lists, of which approximately 75% were cataract cases. Although there is currently a significant shortfall of around 225 consultant ophthalmologists, as defined by the College of Ophthalmologists' standard, the backlog is also due to the imbalance in, and inefficient use of, resources. There are a number of possible ways of clearing the backlog, including local initiatives, contracting for clinical services and the expansion of day case surgery, which has been shown to be a cost-effective alternative to in patient surgery. However, not only are reorganisations in the provision of surgical services required, managerial initiatives also need to be taken. PMID- 1743366 TI - Inter and intra observer reproducibility of the new Oxford CCD Scheimpflug camera. AB - Scheimpflug photography is a well recognised technique for obtaining sagittal views of the anterior structures of the human eye in vivo. A new generation of Scheimpflug camera, which uses a CCD (charge coupled device) instead of film, permitting the digitised image achieved to be directly analysed using computerised linear scanning densitometry, is described. The advantages and present limitations of this system over the older film using system are discussed and the reproducibility of the new CCD system in its ability to measure certain features of the crystalline lens is presented. PMID- 1743367 TI - Maximising the sensitivity and specificity of non-contact tonometry in glaucoma screening. AB - Data from a glaucoma screening study involving 88.5% of the population age 50 and over of a single handed general practitioner were reanalysed to determine the effect of altering the protocol for intraocular pressure assessment and the effect of changing the referral threshold. The predictive power of the Keeler Pulsair noncontact tonometer was found to decrease from 22.5% at four pulses per eye to 12.3% when only one pulse per eye was used, with a reduction of sensitivity from 91.7% to 75%. The sensitivity of the same device fell from 91.7% if all patients with an IOP greater than 21 mmHg were deemed as having a positive screen, to 41.6% when only patients with an IOP greater than 26 mmHg were considered for referral. To create a balance between high sensitivity and acceptable predictive power of a positive result in a population where 50% of glaucoma sufferers are known prior to screening, we advise that four pulses per eye should be used with an IOP of greater than 22 mmHg used as the significant finding indicating that the patient required referral. PMID- 1743368 TI - A new clinical slit lamp reference stand. PMID- 1743369 TI - Lack of pancreatic maldigestion in atopic dermatitis. AB - Twenty adult patients affected by atopic dermatitis (AD) were submitted to the p aminobenzoic acid (PABA) test in order to evaluate the proteolytic pancreatic function. All but one showed a normal PABA test. These results seem to exclude a proteolytic maldigestion as a pathogenetic factor in AD. PMID- 1743370 TI - Malignant melanoma in southern Germany: different predictive value of risk factors for melanoma subtypes. AB - The presented case-control study with 204 melanoma patients and 200 control persons assesses the significance of melanoma risk factors for an ethnically homogeneous population from a geographically small region. In a multivariate analysis of the data the total number of benign naevi proved to be the most predictive parameter with a relative risk (RR) of 14.9 (total number of naevi higher than 50). The constitutional factors red hair colour and skin type 1 were less predictive with an RR of 2.9 and 4.9, respectively. Occupational and recreational sun exposure were of ancillary importance (RR 1.8 and 2.1). The assessment of the risk for the subtypes of melanoma however showed a clear difference in the predictive value of the mentioned risk factors. The risk of developing superficial spreading melanoma is nearly exclusively defined by the number of benign naevi (RR 24.8), red hair colour was of subordinate importance (RR 4.2), whereas the risk of lentigo maligna melanoma is dependent on skin type 1 (RR 12.9) and sun exposure (RR 3.4). PMID- 1743371 TI - Primary localized cutaneous nodular amyloidosis: case report and biochemical analysis of amyloid. AB - We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000 dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both kappa and lambda light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both kappa and lambda immunoglobulin light chains. PMID- 1743372 TI - Lack of correlation between in vitro immunological alterations and the development of scleroderma-like skin lesions in toxic oil syndrome patients. AB - We examined whether immunological disturbances could influence the development of scleroderma-like skin lesions in patients affected by the Spanish toxic oil syndrome (TOS). To this end, peripheral blood mononuclear cells (PBMC) were collected from 13 chronic patients and 8 control subjects. All patients had suffered a toxic-induced severe neuromyopathy, and 6, in addition, had developed sclerodermoid skin manifestations. The phenotypic profile and the concentrations of interleukin-2 (IL-2) and of molecules with B cell differentiation factor IgG activity (BCDF-IgG) in supernatants of phytohemagglutinin-stimulated lymphocytes were analyzed both in patients and in normal controls. Molecules with BCDF-IgG activity were found increased in supernatants of mitogen-stimulated lymphocytes from TOS patients. Concentrations of IgG secreted by staphylococcus aureus-SAC-B blasts in the presence of TOS PBMC supernatant was 88 +/- 32.62 ng/ml (mean +/- 1 SD) versus 53 +/- 5.34 ng/ml in the presence of control supernatant (p less than 0.01). Levels of BCDF-IgG activity in TOS PBMC supernatants positively correlated with IgG serum levels (r = 0.69, p less than 0.01). The phenotypic profile of lymphocyte populations and the production of IL-2 were not altered in TOS subjects. No statistically significant differences were observed in the lymphocyte distribution nor in the IL-2 and BCDF-IgG production when comparing patients with or without scleroderma-like skin lesions. The results indicate that there was a dysfunction of the immune response in TOS subjects, which, however, was not sufficient for the development of the sclerodermoid lesions. PMID- 1743373 TI - Topical tretinoin decreases healing times of electroepilation-induced wounds. AB - There is evidence that topical tretinoin promotes wound healing, especially when the wound area is pretreated. In our study, 5 patients were pretreated for 2 weeks with 0.05% tretinoin cream to one groin or axilla, followed by electroepilation to both sides. Electroepilation created small, superficial wounds. Healing was defined as complete re-epithelialization. In all patients the pretreated side showed a significantly decreased healing time as compared to the nonpretreated side. Pretreatment of skin with topical tretinoin may be useful in reducing healing times of patients undergoing electroepilation. PMID- 1743374 TI - Intravenous single-dose ceftriaxone treatment of chancroid. AB - The antimicrobial susceptibility of Haemophilus ducreyi varies according to the geographic region. Increased resistance to trimethoprim and/or sulfamethoxazole led the Centers for Disease Control to recommend 250 mg ceftriaxone as a single intramuscular dose for chancroid. Intravenous or muscular routes of administration result in equivalent bioavailability. To avoid side effects such as syringe abscess and lidocaine intolerance, we prefer intravenous ceftriaxone therapy. The efficacy of this regimen is reported in 3 cases of chancroid. The intravenous administration of 1 g of ceftriaxone in chancroid seems to be as effective as administration by the intramuscular route, but it may lower the risk of syringe abscess, lidocaine intolerance and the emergence of resistant strains. PMID- 1743375 TI - Nucleolar organizer regions argyrophilic associated proteins in cutaneous melanocytic lesions. AB - We applied a simple silver staining technique to visualize nucleolar organizer regions associated proteins (AgNORs) for the study of 47 melanocytic lesions (20 malignant melanomas, 5 dysplastic nevi, 4 Spitz nevi, 2 Reed and Gartman's fusiform nevi and 16 melanocytic nevi). A statistically significant difference existed between the numbers of AgNORs per cell in benign and malignant lesions as a group. However, some overlapping counts were found, limiting the usefulness of the technique in differentiating benign from malignant lesions in individual cases. PMID- 1743376 TI - Dermatomyositis and pregnancy. Case report and review of the literature. AB - Dermatomyositis is a rare disease complicating pregnancy. We treated a patient in whom two pregnancies were complicated by dermatomyositis. In the first of the two gestations, a mild form of the disease arose in the last trimester. In the second gestation, the disease was inactive following treatment with 0.3 mg/kg/day prednisolone. Both the mother and two children have since been doing well. PMID- 1743377 TI - Subcutaneous leiomyosarcoma developing in a radiation dermatitis. AB - A case of subcutaneous leiomyosarcoma developing in a skin affected by radiation dermatitis is presented. A 59-year-old patient had been suffering from radiation dermatitis induced by radiotherapy for a mediastinal tumor diagnosed at 24 years of age. Thirty-four years later, slow growing nodules developed in this lesion. Light and electron microscopic studies revealed that the tumor was a subcutaneous leiomyosarcoma. There is no previous report of a subcutaneous leiomyosarcoma developing in radiation dermatitis. PMID- 1743378 TI - Stratum corneum lipid function. AB - The stratum corneum contains a complex mixture of polar and nonpolar lipids in its intercellular spaces. These lipids, present in form of multiple lamellae, have been investigated for their role in providing the epidermal barrier to transcutaneous water loss, the selective barrier from the inside to the outside of the organism and partly the process of physiological desquamation. The composition of these lipids varies from species to species, with the body region and the degree of keratinocyte differentiation. The most undifferentiated layers of the epidermis contain typical membrane lipids, phospholipids, while more differentiated layers contain ceramides, cholesterol and free fatty acids. Essential fatty acids are essential for the maintenance of the lamellar structures and epidermal barrier function. Epidermal linoleic and arachidonic acids derive from exogenous sources. Only recently attempts have been made to elucidate the timing and regulation of epidermal fatty acid metabolism. Keratinocytes do not express a low molecular weight fatty acid binding protein like other cells active in lipid metabolism, but may employ alternative ways in fatty acid uptake and metabolism. PMID- 1743379 TI - The skin: an immunoreactive target organ during interleukin-2 administration? AB - Six patients with metastatic malignant melanoma were treated systemically with dacarbazine and interleukin-2 (IL-2). During IL-2 administration all patients developed a macular erythematous rash followed by scaling which began 24-48 h after IL-2 infusion. The dermatological changes were associated with elevated interferon-gamma and tumor necrosis factor alpha serum levels (immunoradiometric assay). Histology revealed nonspecific spongiotic foci in the epidermis and a perivascular mononuclear infiltrate in the dermis. Immunohistochemistry characterized this infiltrate mainly as activated T helper lymphocytes and revealed the expression of intercellular adhesion molecule 1 by endothelial cells and keratinocytes that might have been induced by interferon-gamma. The skin reactions associated with systemic IL-2 administration, show that the skin actually participates as a target organ. They should be differentiated from drug eruptions. PMID- 1743380 TI - Noninvasive procedures in dermatology. Potential infective risks and need for sterility. AB - Although in the area of incisional surgery the level of sterile techniques has improved in recent years and approaches that of the surgical standards in other specialties, one cannot say the same with regard to some of the nonsurgical or semisurgical procedures. Here, unfortunately, there are even no standards to aim for and no guidelines to adopt. Since in the field of nonsurgical cosmetic skin care dermatologists have a unique position, we alone must shoulder the responsibility for setting the standards and determining the appropriate conditions for carrying out these procedures. Unfortunately, it appears that in certain of the dermatologic procedures not involving actual skin incision, the level of sterility has not improved for decades. In such dermatologic procedures there are marked discrepancies between the care taken to maintain a high degree of sterility of instruments that penetrate the skin, compared with the lack of attention to sterility of instruments that do not directly penetrate the skin and the area surrounding the procedure site. It seems that the guiding principle we must strive for is to prevent the transmission of infection from one patient to another. The emphasis should be not on sterility per se but on the prevention of transmission of disease from patient to patient. PMID- 1743381 TI - Early detection of scleroderma spectrum disorders in patients with Raynaud's phenomenon. AB - Fifty patients with the chief complaint of Raynaud's phenomenon (RP) presented at our scleroderma clinic from March to December 1990. Physical examination, routine laboratory tests (blood, urine and chest X-ray), determination of the pattern of RP, antinuclear antibody (ANA) tests and examination for nailfold bleeding were performed. Three patients were diagnosed as having systemic sclerosis sine scleroderma, 15 patients as having RP with positive anticentromere antibody and 6 patients as having an incomplete form of mixed connective tissue disease. Thus, a total of at least 24 patients out of 50 (48%) were shown to have a scleroderma spectrum disorder. A definite RP pattern (triphasic or biphasic and bilateral), positive ANA and positive nailfold bleeding were strongly correlated statistically, suggesting that these are simple useful findings for the early detection of scleroderma spectrum disorders in patients with RP. We expect that there are many undiagnosed patients with an early-stage scleroderma spectrum disorder in the general population. PMID- 1743382 TI - A new classification of Ota's nevus based on histopathological features. AB - According to the distribution of the dermal melanocytes, Ota's nevus was classified into 5 types: superficial (type S), superficial dominant (type SD), diffuse (type Di), deep dominant (type DD), and deep (type De). The histological types were, as expected, relatively well-correlated with the color of the nevus: the most brownish lesions represented type S or type SD, while the most bluish lesions showed types Di, DD or De. Furthermore these types were strongly correlated with the location of the nevus: types S and SD were more frequent on cheeks, whereas types Di, DD and De more frequently occurred on eyelid, temple and forehead. When combining both colorations and locations of the nevus, our classification appeared much more significant. Our new histological classification of Ota's nevus may be very useful in making a therapeutic prognosis of the disease. PMID- 1743383 TI - The epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH inhibits murine hair growth in vivo and in vitro. AB - Tissue growth may be controlled by negative feedback mechanisms. Recently, a pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH ('epidermal pentapeptide', EPP), which slows the growth of mouse epidermis in vivo and of mouse keratinocytes in vitro, was isolated from mouse epidermis. Since inhibitory molecules like EPP might be part of the feedback systems underlying hair growth control, we assessed the effect of synthesized EPP on the growth of hair follicles, using rodent in vivo and in vitro assays. We report for the first time that intraperitoneally injected EPP (30 nmol/animal/day over 6 days) significantly slows the growth of hair follicles in plucking-induced anagen skin of C57 B1-6 mice (as assessed by microscopic morphometry). Using an in vitro organ culture assay, EPP inhibits the incorporation of 3H-thymidine into mouse pelage anagen follicles. That this epidermal-derived peptide affects hair growth raises the possibility that hair growth may be regulated by an inhibition/disinhibition mechanism under participation of EPP-like molecules and that the epidermis may play a role in the control of hair growth. PMID- 1743384 TI - Effect of non-enzymatic glycosylation and heating on browning of human stratum corneum and nail. AB - The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control), 10 (only nail), 20 (only nail), 100 and 250 mM glucose buffer at 37 degrees C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 degrees C for 14 days. Browning of the stratum corneum was assessed macroscopically, and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances. Munsell's scores (H = hue score, V = lightness score, C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 degrees C did not show visible browning. Munsell's score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + C)/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients. PMID- 1743385 TI - Skin lesions in carbon monoxide intoxication. AB - A 25-year-old man who survived carbon monoxide intoxication presented erythematous cutaneous lesions with blister formation in pressure areas. Histologic examination revealed subepidermal vesicles with extensive sweat gland necrosis. We discuss the clinicopathological findings of carbon monoxide poisoning. Similar cutaneous features have been observed in patients with various kinds of drug-induced coma. PMID- 1743386 TI - Pemphigus erythematosus with suprabasilar acantholysis and lichenoid tissue reaction or a combination of pemphigus vulgaris and lupus erythematosus: a new entity? AB - We present a 36-year-old woman with pemphigus erythematosus that showed histopathologically supra-basilar acantholysis and lichenoid tissue reaction. To our knowledge this is the first case of pemphigus erythematosus with such unusual histopathologic presentation to be reported. PMID- 1743387 TI - Cogan's syndrome. An unusual etiology of urticarial vasculitis. AB - We report the case of an 18-year-old black woman with urticarial vasculitis, vestibuloauditory dysfunction and superficial keratitis. Oral steroid therapy was effective in reducing most clinical manifestations with high-dosage dependency. However, only intravenous pulses of methylprednisolone allowed slight improvement of hearing. In this case, we emphasize urticarial vasculitis as a new manifestation of atypical Cogan's syndrome. A significant titer of Chalmydia trachomatis antibodies was found in our patient: their role in the pathogenesis of Cogan's syndrome is discussed. PMID- 1743388 TI - Cutaneous ulceration: an unusual complication of intravenous pentamidine therapy. AB - Pentamidine is one of two agents currently used to treat infections with Pneumocystis carinii. The intramuscular route of administration is associated with cutaneous side effects such as dermal necrosis, sterile abscesses and ulcer formation at the injection site, while urticaria may develop near the site of intravenous drug infusion. This is a report of a renal transplant patient with Pneumocystis pneumonia who developed chemical cellulitis and ulceration following the extravasation of intravenous pentamidine into the soft tissues of the left hand and forearm. The area healed slowly over 7 weeks, but there was a residual loss of cutaneous sensation. In a review of the literature no report of a similar case was found. PMID- 1743389 TI - Concomitant granuloma annulare and necrobiosis lipoidica. Report of a case and review of the literature. AB - A case of concomitant granuloma annulare (GA) and necrobiosis lipoidica (NL) is presented. The etiology of these two disorders remains obscure. The similarity of the histopathology in GA and NL might suggest a common origin. However, a review of the 5 previous cases of concomitant GA and NL and recent biochemical, immunological and immunohistochemical studies comparing GA to NL indicates an independent etiology for these two histologically related disorders. Some evidence points toward a closer relationship of NL with diabetes than GA, while GA may be related to delayed-type hypersensitivity reactions. PMID- 1743390 TI - Atypical neutrophilic dermatosis on the upper extremity affected by postmastectomy lymphedema: report of 2 cases. AB - We describe 2 female patients, both with a history of radical mastectomy for breast cancer, in whom several indurated erythematous plaques developed on the upper extremity affected by postmastectomy lymphedema. There were no general symptoms or leukocytosis. Histopathological examination showed a dense neutrophilic infiltrate without a feature of vasculitis in the dermis and subcutis. Dramatic therapeutic response was observed to treatment with potassium iodide. These findings resemble Sweet's syndrome, but such cases have not been previously reported. Possible pathogenic mechanisms for these unique cutaneous eruptions are discussed. PMID- 1743391 TI - Incontinentia pigmenti with hyperkeratotic lesions in adulthood and possible squamous cell carcinoma. AB - A case of incontinentia pigmenti with extensive and progressive hyperkeratotic lesions at the age of 25 years is reported. The histology showed a keratoacanthoma-like picture and signs compatible with squamous cell carcinoma. To our knowledge this has not been previously reported. PMID- 1743392 TI - Conjugal blocks in Tetrahymena pattern mutants and their cytoplasmic rescue. I. Broadened cortical domains (bcd). AB - The cortical pattern mutant broadened cortical domains (bcd) in Tetrahymena thermophila is unable to complete the nuclear events associated with conjugation. bcd x bcd pairs become arrested at the "nuclear exchange" configuration. Genetic analysis reveals that the bcd conjugal block is 100% penetrant, under macronuclear control, and rescueable (a) by outcrossing to a wild-type partner, (b) by administration of a hyperosmotic shock 5 hr after cells are mixed for mating, or (c) by cytoplasmic transfusion from a wild-type donor. Cytological analysis reveals that the conjugal block is primarily the result of failure in pronuclear fusion (karyogamy). bcd pairs also exhibit reduced nuclear exchange efficiency and a failure of macronuclear anlagen formation. The hypothesis is proposed that the bcd+ gene codes for a microtubule-based organelle "motor" similar to kinesin. PMID- 1743393 TI - Conjugal blocks in Tetrahymena pattern mutants and their cytoplasmic rescue. II. janus A. AB - A conjugal block phenotype is described for the Tetrahymena pattern mutant, janA. janA exhibits a characteristic "janus" phenotype in which cells develop with a global mirror-image duplication of the ventral pattern of cortical organelles. janA cells are competent to form mating pairs, but later become irreversibly fused as heteropolar doublets. The few pairs that successfully dissociate fail to undergo postconjugal oral replacement and perish. The janA conjugal block is 100% penetrant, is under prezygotic macronuclear control, and is lethal. Here we characterize this conjugal block genetically and cytologically and demonstrate that it can be rescued by a transferable, wild-type product. New insights into late conjugal events, especially the replacement of the oral apparatus, are reported for wild-type cells as well. PMID- 1743394 TI - A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. AB - The present study represents the first comprehensive analysis of isoactin gene expression in the developing rat. Our results clearly demonstrate that the developmental and tissue-specific expression of the actin multigene family is a highly integrated and complex process involving a variety of regulatory paradigms. The distinct temporal patterns of expression reported in this study indicate that there are three key phases in the regulation of expression of the actin multigene family during development. These include early embryonic development, late fetal development, and early postnatal development. The specific spatial patterns of expression observed in this study demonstrate that the expression of the actin multigene family is much more permissive than previously reported. This permissive expression includes a wide range of "ectopic" expression of the striated muscle isoactins as well as an extended expression of the alpha-smooth muscle isoactin. These findings expand our current understanding of the expression of the actin multigene family in development and provide a fundamental basis for future studies directed at investigating these processes. PMID- 1743395 TI - Characterization of a cDNA encoding a protein involved in formation of the skeleton during development of the sea urchin Lytechinus pictus. AB - In order to investigate the role of proteins in the formation of mineralized tissues during development, we have isolated a cDNA that encodes a protein that is a component of the organic matrix of the skeletal spicule of the sea urchin, Lytechinus pictus. The expression of the RNA encoding this protein is regulated over development and is localized to the descendents of the micromere lineage. Comparison of the sequence of this cDNA to homologous cDNAs from other species of urchin reveal that the protein is basic and contains three conserved structural motifs: a signal peptide, a proline-rich region, and an unusual region composed of a series of direct repeats. Studies on the protein encoded by this cDNA confirm the predicted reading frame deduced from the nucleotide sequence and show that the protein is secreted and not glycosylated. Comparison of the amino acid sequence to databases reveal that the repeat domain is similar to proteins that form a unique beta-spiral supersecondary structure. PMID- 1743396 TI - Extracellular matrix (mesoglea) of Hydra vulgaris. I. Isolation and characterization. AB - Hydrozoans such as Hydra vulgaris, as with all classes of Cnidaria, are characterized by having their body wall organized as an epithelial bilayer with an intervening acellular layer termed the mesoglea. The present study was undertaken to determine what extracellular matrix (ECM) components are associated with Hydra mesoglea. Using polyclonal antibodies generated from vertebrate ECM molecules, initial light and electron microscopic immunocytochemical studies indicated the presence of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin immunoreactive components in Hydra mesoglea. These immunocytochemical observations were in part supported by biochemical analyses of isolated Hydra mesoglea which indicated the presence of fibronectin and laminin based on Western blot analysis. Amino acid analysis of total mesoglea and some of its isolated components confirmed the presence of collagen molecules in mesoglea. Additional studies indicated the presence of (1) a gelatin binding protein in Hydra which was immunoreactive with antibodies raised to human plasma fibronectin and (2) a noncollagen fragment extracted from mesoglea which was immunoreactive to antibodies raised to the NC1 domain (alpha 1 subunit) of bovine glomerular basement membrane type IV collagen. These observations indicate that Hydra mesoglea is evolutionarily a primitive basement membrane that has retained some properties of interstitial ECM. PMID- 1743397 TI - Extracellular matrix (mesoglea) of Hydra vulgaris. II. Influence of collagen and proteoglycan components on head regeneration. AB - Hydra are characterized by having their body wall organized as an epithelial bilayer with an intervening acellular layer termed the mesoglea. As an extension of the previous study which indicated that mesoglea is a primitive basement membrane which has retained some characteristics of interstitial extracellular matrix, the present study was undertaken to analyze the role of mesoglea components during head regeneration in Hydra vulgaris. Studies were conducted that utilized drugs that affect collagen processing or secondary collagen structure (beta-aminoproprionitrile; 2,2'-dipydridyl; and cis-4-hydroxy-L proline) and a drug that inhibits addition of glycosaminoglycan chains to proteoglycan core proteins (p-nitrophenyl-beta-D-xylopyranoside). These studies indicated that alterations in the structure of collagens or proteoglycans caused blockage of head regeneration in Hydra as monitored over a 48-hr period. Blockage of head regeneration was reversible once the drugs were removed, indicating that the drugs were not having a general toxic effect on the organism. Radiotracer studies also indicated that blockage of head regeneration was not simply due to a general depression of protein synthesis by the drugs. Various controls indicated that each drug was affecting mesoglea components under the conditions utilized in these studies. These observations indicate that preservation of normal mesoglea structure is required for Hydra head regeneration to proceed. PMID- 1743398 TI - Interstitial stem cell proliferation in hydra: evidence for strain-specific regulatory signals. AB - We have examined the growth behavior of small numbers of interstitial stem cells transplanted into tissue of genetically unrelated strains of Hydra magnipapillata. We show that such stem cells, which are at low density following transplantation, proliferate more rapidly than the stem cells of the host, which are at normal density. The rapid proliferation is similar to the proliferation rate of stem cells transplanted into interstitial cell free tissue. The results suggest that stem cells transplanted into heterotypic tissue are unable to "sense" the presence of host stem cells and to adopt their growth rate to that of the surrounding cells. Thus, the feedback signal which negatively regulates stem cell growth as a function of stem cell density must be strain specific. PMID- 1743399 TI - Developmental analysis of ocular morphogenesis in alpha A-crystallin/diphtheria toxin transgenic mice undergoing ablation of the lens. AB - The role of the lens in early eye development was examined in transgenic mice carrying the cytotoxic diphtheria toxin A gene driven by hamster alpha A crystallin promoter sequences. Mice hemizygous for this construct are microphthalmic and contain a vacuolated and highly disorganized lens, whereas adult homozygous mice are completely ablated of the lens and lack a pupil, aqueous and posterior chamber, vitreous humor, iris, and ciliary body and show extensive convolution of the sensory retina. Developmental analysis of animals homozygous for the transgene revealed that the optic cup and lens vesicle form normally and that ablation of the lens occurs as a gradual degenerative process beginning between Days 12 and 13 of gestation. Degeneration of the lens vesicle coincides with retarded growth and development of the neuroretina, sclera, and cornea. The anterior lip of the optic cup fails to differentiate into the normal epithelium of the iris and ciliary body and the vitreous body does not develop. Although the retinal layers apparently form normally, retinal folding becomes prominent following lens degeneration. These results suggest that development of a functional lens from Embryonic Day 12.5 onward is critical for formation of the ciliary epithelium, iris, and vitreous body, as well as for appropriate growth, development, and maintenance of morphology of the retina, cornea, sclera, and optic nerve. Our results also provide information on the time course of DT-A mediated cell destruction in vivo and are discussed in context with previous lens ablation studies and the importance of developmental analysis for interpretation of the extent to which morphogenetic aberrations are concurrent with or secondary to genetic ablation of the target tissue. PMID- 1743400 TI - A gradient of gap junctional communication along the anterior-posterior axis of the developing chick limb bud. AB - A modification of the scrape-loading/dye transfer technique was used to study gap junctional communication along the anterior-posterior (A-P) axis of embryonic chick wing buds at an early stage of development (stage 20/21) when positional values along the A-P axis are being specified. Extensive intercellular transfer of the gap junction-permeable dye, lucifer yellow, from scrape-loaded mesenchymal cells to contiguous cells occurs in the posterior mesenchymal tissue of the wing bud adjacent to the zone of polarizing activity, which is thought to be the source of a diffusible morphogen that specifies A-P positional identity according to its local concentration. Considerably less transfer of lucifer yellow dye occurs in scrape-loaded mesenchymal tissue in the middle of the limb bud compared to posterior mesenchymal tissue, and little or no transfer of lucifer yellow is observed in the mesenchymal tissue in the anterior portion of the limb bud. No intercellular transfer of the gap junction-impermeable dye, rhodamine dextran, occurs in any region of the limb bud. These results indicate that there is a gradient of gap junctional communication along the A-P axis of the developing chick wing bud. This gradient of gap junctional communication along the A-P axis might generate a graded distribution of a relatively low molecular weight intracellular regulatory molecule involved in specifying A-P positional identities. PMID- 1743401 TI - In situ hybridization studies on the expression of type X collagen in fetal human cartilage. AB - Type X collagen is a short, non-fibril-forming collagen restricted to the hypertrophic, calcifying zone of growth plate cartilage. It is developmentally regulated and found exclusively in hypertrophic cartilage. Here we report on the structure and distribution of human type X collagen based on the cloning of a PCR fragment covering 292 bp of the carboxy-terminal, non-triple-helical domain. Seventy-five percent of the sequence are identical to that of chicken type X collagen at nucleic acid level and 84% at amino acid level. This probe was used for in situ hybridization analyses of type X collagen expression in a human growth plate. Human fetal cartilage, which is different from the avian cartilage bone transition zone, showed strong type X collagen expression confined to the lower hypertrophic zone of the growth plate. The upper zone of hypertrophic chondrocytes did not contain alpha 1(X) transcripts, indicating that type X collagen expression follows cellular hypertrophy. The distribution of type X collagen mRNA has been previously unreported in chondrocytes from zones of secondary ossification and in chondrocytes associated with endochondral bone trabecules containing calcified cartilage. In situ hybridization analyses with probes for type I and II collagen on consecutive sections indicated a spatial gradient in chondrocyte differentiation in the human epiphysis. Chondrocytes of low type II collagen expression in the resting zone are followed by proliferating columnar chondrocytes with strong type II collagen expression and a zone of hypertrophic chondrocytes synthesizing type X and type II collagen. In contrast to findings in avian growth cartilage in some of our samples of human epiphyseal cartilage hypertrophic chondrocytes continued to strongly express type II collagen down to the chondro-osseous junction. Transcripts of the alpha 2(I) collagen gene, however, were detected only in perichondrium, vascular cavities, and bone, but not in hypertrophic or any other chondrocytes. The above observations demonstrate that the isolation of the human type X collagen DNA will contribute to studies of pathways of chondrocyte differentiation in the mammalian growth plate. PMID- 1743402 TI - Directional mesoderm cell migration in the Xenopus gastrula. AB - The movement of the dorsal mesoderm across the blastocoel roof of the Xenopus gastrula is examined. We show that different parts of the mesoderm which can be distinguished by their morphogenetic behavior in the embryo are all able to migrate independently on the inner surface of the blastocoel roof. The direction of mesoderm cell migration is determined by guidance cues in the extracellular matrix of the blastocoel roof and by an intrinsic tissue polarity of the mesoderm. The mesodermal polarity shows the same orientation as the external guidance cues and is strongly expressed in the more posterior mesoderm. The guidance cues of the extracellular matrix are recognized by all parts of the dorsal mesoderm and even by nonmesodermal cells from other regions of the embryo. The extracellular matrix consists of a network of fibronectin-containing fibrils. The adhesiveness of this matrix does not vary along the axis of mesoderm movement, excluding haptotaxis as a guidance mechanism in this system. However, an intact fibronectin fibril structure is necessary for directional mesoderm cell migration. When the assembly of fibronectin into fibrils is inhibited, mesoderm explants still migrate on the amorphous extracellular matrix, but no longer directionally. It is proposed that polarized extracellular matrix fibrils may normally guide the migrating mesoderm to its target region. PMID- 1743403 TI - Pattern of epithelial cell cycling in hydra. AB - We have investigated the spatial pattern of epithelial cell cycling in a mutant strain of Hydra magnipapillata (sf-1). This strain has temperature sensitive interstitial stem cells and thus polyps containing only epithelial cells can be obtained by growth at the restrictive temperature. Epithelial animals were pulse labeled with the thymidine analog 5'-bromo-2'-deoxyuridine (Brdu) and stained with anti-Brdu antibody to visualize S phase cells. Our results indicate that Brdu-labeled cells are broadly and fairly evenly distributed along the body column. Feeding stimulates a rapid decrease and then an increase in labeled cells in gastric tissue; labeled cells in the head are not affected. Starvation leads to a twofold decrease in labeled cells in the gastric region; the density of labeled cells in head tissue remains similar to that in well-fed animals. During bud formation the number of labeled epithelial cells increases significantly in the evaginating bud. During head regeneration the number of labeled cells declines sharply during the first 12 hr and then increases to a density typical of head tissue by 24-36 hr of regeneration. The results indicate the release of signals by feeding and regeneration which inhibit mitosis. By contrast head tissue and developing buds express signals stimulating mitosis. Thus changes in epithelial cell cycling in hydra are closely correlated with morphogenetic events as well as with feeding stimuli. PMID- 1743404 TI - A cytoplasmic gradient of Ca2+ is correlated with the growth of lily pollen tubes. AB - We have measured the distribution of cytoplasmic calcium in lily pollen tubes by microinjecting them with indo-1 and performing fluorescence ratio image analysis on them. All of the 16 tubes that were growing at the time of the calcium measurements showed a gradient of [Ca2+]i in the tip region, with Ca2+ being 1.25 to 3.32 times higher at the distal end in 15 cases and more than 5 times higher in one case. The extent of the gradient ranged from 22 to 65 microns. Most of the 15 nongrowing tubes either had no gradient or had lower Ca2+ in the tip region. While we have confirmed a previous report that lily pollen tubes can be loaded with the membrane-permeable acetoxymethyl ester forms of calcium indicators, the dyes loaded in this way are visibly partitioned into organelles and this method of loading is, therefore, not useful for the measurement of [Ca2+]i. Iontophoresis of the dye free acids into tubes produces a more uniform and diffuse fluorescence which does not appear to partition into organelles. Indo-1 remains in the pollen tubes longer than fura-2. The correlation between growth and the [Ca2+]i gradient in the apical portion of the pollen tube is discussed in relation to previous reports that have suggested that such a gradient should exist during polarized growth. PMID- 1743405 TI - Effects of exogenous putrescine on murine preimplantation development in vitro. AB - After first demonstrating that murine embryos take up putrescine from the medium in which they are cultured in vitro, fertilized eggs were placed in culture and maintained for 4 days in medium supplemented with varying amounts of putrescine. Their development was monitored each day. While embryos that were cultured in putrescine-supplemented medium developed at the same rate as control embryos, a significantly higher percentage of the putrescine-treated embryos attained the blastocyst stage as compared to the control group. PMID- 1743406 TI - Sea urchin USF: a helix-loop-helix protein active in embryonic ectoderm cells. AB - We previously characterized a DNA-binding factor in nuclear extracts of Strongylocentrotus purpuratus embryos that bound Spec gene promoters, was ectoderm specific, and had properties similar to the vertebrate transcription factor USF. Here we describe a cDNA clone, suUSF, isolated from an S. purpuratus cDNA library, with sequence homology to human USF. Spec gene promoter fragments formed sequence-specific complexes with suUSF, and antibodies against suUSF inhibited binding activity in nuclear extracts. Reaction of USF-site containing probes with filter-bound nuclear proteins demonstrated that suUSF binding activity was enriched in ectoderm cells, and immunoblotting showed a similar ectoderm enrichment. These data demonstrated that suUSF was responsible for the ectoderm-specific activity observed in sea urchin extracts. PMID- 1743407 TI - Myelination as an expression of the functional maturity of the brain. AB - A prospective cross-sectional study was performed on hydrocephalic infants and children. MRI was used to assess the state of myelination and to quantify the intracranial cerebrospinal fluid (CSF) volume repeatedly in all children. At the same time, neurodevelopmental testing was performed. A positive correlation was found between the progress of myelination and psychomotor development, but there were no significant correlations between CSF volume and myelination or between CSF volume and psychomotor development. This study provides strong evidence in favour of Flechsig's thesis that myelination expresses the functional maturity of the brain. The interdependency of neuronal maturation and progress of myelination are discussed. PMID- 1743408 TI - Outcome after childhood encephalitis. AB - The prognosis for 73 children treated for encephalitis between 1973 and 1983 was evaluated. 70 children participated in a follow-up examination 2.4 to 12.9 years after the acute phase of the disease. The 61 school-aged children had lower performance and full-scale IQs than their randomly selected, age- and sex-matched controls. Visual acuity was more often reduced, and they more often had focal slowing on EEG and electronystagmogram abnormalities. Clinically, these differences were not significant. Encephalitis with a poor prognosis occurred seldom, the incidence being 3.5 cases per one million children at risk annually. These results show that the prognosis for childhood encephalitis is much better than anticipated on the basis of experience mainly with herpes simplex virus encephalitis. PMID- 1743409 TI - Simple developmental speech delay: a follow-up study. AB - The authors followed 38 children with delayed speech development approximately two to four years after initial diagnosis, assessing and comparing their subsequent speech and language, and over-all development. Nearly all of the children had appropriate language levels for their general development. Just over half had less articulation competence than expected for their age, but this was not related to language achievement or age. It appears that the prognosis for future language development is favourable for these children. The results suggest that articulation might be a developmentally related process with a good prognosis, but further follow-up is necessary to determine ultimate competence of children in whom this is delayed. PMID- 1743410 TI - Low to moderate maternal alcohol use before and during pregnancy, and neurobehavioural outcome in the newborn infant. AB - Of 2002 randomly selected pregnant women recruited prospectively over a three year period for an extensive questionnaire survey, a stratified subsample of 665 mothers was selected for mother-infant follow-up on the basis of pre-pregnancy alcohol intake. Infant outcome was assessed by detailed clinical examination and application of a modified Einstein Neonatal Behavioural Assessment Schedule (ENBAS) performed at 24 to 72 hours of age. Of the infant responses to 25 ENBAS items, only tonus showed a small but significant relationship to pre-pregnancy maternal alcohol intake. The authors conclude that low to moderate maternal alcohol intake has no significant effect on newborn neurological status. PMID- 1743411 TI - Head circumference and intellectual performance of patients with Duchenne muscular dystrophy. AB - The head circumferences of 64 patients with Duchenne muscular dystrophy were measured and found to be greater than those of a normal population. The patients had relative, and in 12 cases, absolute macrocephaly. 47 of the 64 patients underwent intelligence testing and were found to be significantly intellectually impaired, particularly in verbal and language skills. There was no correlation between head circumference or absolute macrocephaly and intellectual performance. The cause of macrocephaly in these patients is unknown and its relevance to the aetiology of intellectual impairment in Duchenne muscular dystrophy is not yet clear. PMID- 1743412 TI - Developmental patterns of normal nutritive sucking in infants. AB - The purpose of this investigation was to quantify normal nutritive sucking, using a microcomputer-based instrument which replicated the infant's customary bottle feeding routine. 86 feeding sessions were recorded from infants ranging between 1.5 and 11.5 months of age. Suck height, suck area and percentage of time spent sucking were unrelated to age. Volume per suck declined with age, as did intersuck interval, which corresponded to a more rapid sucking rate. This meant that volume per minute of sucking time was fairly constant. The apparatus provided an objective description of the patterns of normal nutritive sucking in infants to which abnormal sucking patterns may be compared. PMID- 1743413 TI - Psychological characteristics of Sotos syndrome. AB - A preliminary investigation of the psychological characteristics of 16 children aged between five and 15 years who met the strict diagnostic criteria for Sotos syndrome demonstrated that, while cognitive abilities vary, there are behavioural patterns that are characteristic of the disorder. The children were reported to have high rates of behavioural disturbance at home, particularly tantrums, destructiveness, social withdrawal, and eating and sleeping difficulties. The children were reported to present fewer problems in the school environment. Other difficulties expressed by parents are also described and quantified. PMID- 1743414 TI - Leg movements in the supine position of infants with spastic diplegia. AB - Leg movements in the supine position of 49 infants with spastic diplegia (three to 11 months corrected age) were examined. Only simultaneous flexion and extension of the hips and knees were seen, with exceptional isolated hip movements; the simultaneous movements had synergic features. When the knees were flexed, the hips were flexed, abducted and externally rotated, and the ankles were dorsiflexed. When the knees were extended, the hips were extended, adducted and internally rotated and the ankles were plantar-flexed. Hip flexion combined with knee extension (leg elevation) and isolated knee movements were not seen in diplegic infants, but were seen in all control preterm infants with a good prognosis, after five and six months corrected age, respectively. The absence of these movements is a useful diagnostic item for spastic diplegia. PMID- 1743415 TI - Purine metabolites and pyrimidine bases in cerebrospinal fluid of children with simple febrile seizures. AB - Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels. PMID- 1743416 TI - Severe gastric distension in seven patients with cerebral palsy. AB - This is a report of two children who had severe recurrent gastric distension and vomiting, and five who experienced severe gastric distension without vomiting. Two of the five died during an episode of acute gastric distension. All had marked nutritional depletion, and severe spastic quadriplegia due to either cerebral palsy or acquired brain injury. None of the patients had significant gastroesophageal reflux. Positioning the patients in the left lateral decubitus position temporarily relieved their obstructions. Complete resolution of the distension and/or vomiting did not occur until after adequate weight gain. Loss of fat stores may lead to this type of recurrent gastric distension. PMID- 1743417 TI - Severe microcephaly associated with congenital varicella infection. AB - A case of second-trimester congenital varicella infection, in association with isolated microcephaly and severe brain damage, is reported, and cases of classical congenital varicella syndrome are compared on a clinical and immunological basis. This case, together with others cited in the literature, suggests that congenital varicella infection may lead to microcephaly and neurological abnormalities, without the presence of skin lesions. Although first trimester infection has been considered the most likely to produce congenital abnormalities, the second trimester may be more commonly implicated; indeed there may not be a critical period if varicella causes secondary disruption of differentiated tissues. PMID- 1743418 TI - Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. AB - The author describes a previously healthy man who contracted herpes encephalitis at the age of 31 years, and over the following months developed all the symptoms considered diagnostic of autism. This case report casts doubt on the notion of autism as an exclusively developmental disorder. It is suggested that temporal lobe damage may cause autism in some cases. PMID- 1743419 TI - Familial infantile myasthenia: a diagnostic problem. AB - The authors report the diagnostic difficulties experienced with two siblings presenting with recurrent apnoeic attacks caused by the rare condition, familial infantile myasthenia. Standard repetitive nerve stimulation studies were normal in both cases, while changes typical of a subacute neurogenic condition were noted on concentric needle electromyography in one. A 14-day course of pyridostigmine did not elicit any clinical improvement in the elder sibling, in whom tracheomalacia was diagnosed by chest fluoroscopy and bronchoscopy. This infant died at the age of 11 months with hypoxic brain-damage after a severe apnoeic episode. For the second sibling, a positive decremental response was obtained in the hypothenar muscles only after two minutes continuous 10 Hz stimulation of the ulnar nerve. This child has responded well to treatment with pyridostigmine. PMID- 1743420 TI - Examining the evidence for a common structural basis to autism. PMID- 1743421 TI - The spinal muscular atrophies. PMID- 1743422 TI - Familial schizencephaly. AB - Familial cases of schizencephaly hitherto have been associated with readily diagnosable metabolic conditions or malformation syndromes. Where such associations are absent, it is usually considered to be a sporadic event without a genetic contribution. Described here are a brother and sister with identical bilateral symmetrical schizencephaly. Genetic counselling must therefore allow for the possibility of an autosomal recessive form of this condition. PMID- 1743423 TI - Control of drooling with transdermal scopolamine in a child with cerebral palsy. AB - Transdermal scopolamine patches (1.5 mg) were used to control drooling in a two year-old boy with severe spastic quadriparetic cerebral palsy and developmental delay. He responded well to the continuous scopolamine therapy, with a decrease in drooling, and a secondary decrease in respiratory distress and frequency of suctioning. No significant side-effects were noted. PMID- 1743424 TI - Diagnostic issues in autism--are we measuring the emperor for another suit of clothes? PMID- 1743425 TI - The aetiology of intellectual disability in Western Australia: a community-based study. AB - A register of intellectual disability is being established to assess the level and aetiology of intellectual disability in all children born and/or living in Western Australia. 1602 children aged between six and 16 years were identified who had IQs less than 70. 40 per cent had a definite genetic basis, 20 per cent an environmental cause and 40 per cent were of unknown aetiology. The insult was prenatal in 61 per cent, 10 per cent had a possible perinatal cause, 8 per cent were postnatal and for 21 per cent the timing could not be assessed. Approximately 20 per cent had concomitant cerebral palsy and 13 per cent were epileptic. A disparity was found between rural and urban areas, the prevalence being 9.9 and 6.5 per 1000 live births. PMID- 1743426 TI - The predictive value of microcephaly during the first year of life for mental retardation at seven years. AB - Of 41 term infants surviving to seven years of age with head circumferences (HC) 3 SD, 21 were mentally retarded (IQ less than or equal to 70) at seven years. HC - 2 SD was associated with mental retardation in 11 per cent of children. Socio economic status did not affect mental outcome of children with HC - 3 SD, but higher socio-economic level was associated with better outcome for those with HC 2 SD or who were normocephalic. Mental retardation in children with HC - 3 SD was more common in children with additional pathology. Of 25 children with no other pathology, one-quarter were mentally retarded at seven years; this was more common in children of normal birthweight. Disproportionate head-to-height ratio did not significantly affect outcome, although short stature was associated with less favourable outcome for those with HC - 2 SD or who were normocephalic. PMID- 1743427 TI - Normal ranges of hip motion of preterm infants. AB - The hip motion of 158 preterm infants with gestational ages between 25 and 36 weeks was measured. The results of this study, compared with those of previous studies of term infants, show that hip motion changes with increasing gestational age above 25 to 27 weeks. PMID- 1743428 TI - Frontal lobe complex partial seizures in children: a form of epilepsy at particular risk of misdiagnosis. AB - The clinical and EEG findings are described of six children considered to have complex partial seizures of frontal lobe origin. The findings correspond generally with those reported for adult patients. Video-recordings of attacks in some cases and ictal cassette EEG recordings provided important diagnostic information. A definite frontal abnormality on neuro-imaging was seen in only one case. The seizures were closely associated with sleep, and anti-epileptic drug treatment was usually of limited value. The considerable diagnostic confusion surrounding seizures of this type, including their misdiagnosis as pseudoseizures or primary sleep disorder, is partly the result of the clinical peculiarities of this type of seizure, but also of clinicians' limited awareness of the condition. PMID- 1743429 TI - Genomic potential in mammals. AB - Embryos of amphibians, fish, sheep, cattle, swine and rabbits have been multiplied by nuclear transfer. Successful nuclear transfer in these species has been accomplished by transfer of a blastomere from a late stage embryo into an enucleated oocyte or egg with large scale multiplication achieved by serial repetition of the procedure using blastomeres from nuclear transfer embryos. This allows the production of clonal lines, which when appropriately selected for performance in a given trait, can be reproduced to capture in the offspring expression of both additive and nonadditive inheritance. The efficiency of producing offspring from nuclear transfer is low in mammals in both frequency of morula or blastocyst produced and maintenance of pregnancy after embryo transfer. In domestic animals the largest number of offspring from one embryo has been eight calves. Embryos as late as the 64-cell stage in cattle and 120-cell blastocyst in sheep have been used successfully as donors of blastomeres. Recloning has also been done in cattle. Potentially, nuclear transfer provides a mechanism for multiplication and production testing of clonal lines, a method for rapid genetic improvement and a means for rapid propagation of a selected genotype. PMID- 1743430 TI - Temporal and spatial expression of genes for cartilage extracellular matrix proteins during avian mandibular arch development. AB - We have examined the temporal expression of genes for extracellular matrix proteins (type I collagen, type II collagen, and the cartilage specific proteoglycan core protein) during the development of the avian mandibular arch. We detected low levels of type II collagen mRNA in the mandibular arch as early as stage 15. Type II collagen mRNA remained low but increased slightly as development progressed from stage 15 to stage 25. More dramatic increases occurred after stage 25 coincident with overt chondrogenesis. In contrast, mRNA for the core protein of cartilage specific proteoglycan was not detected prior to the onset of chondrogenesis, appeared at stage 25, and increased thereafter. Type I collagen mRNA was also present as early as stage 15 and dramatically increased after stage 28/29, coincident with initiation of osteogenesis. Using in situ hybridization, we found that type II collagen mRNA became detectable in the center of the mandible around stage 24/25 coincident with the initiation of chondrogenesis. At later stages (26-32) type II collagen mRNA was localized in the cartilaginous rudiment. The pattern of hybridization observed with the proteoglycan core protein probe at later stages of development was essentially identical to that observed with the type II collagen probe. In contrast, the probe for the alpha 1 (I) collagen mRNA was localized over the perichondrium, over differentiated bone, and in areas within the mandibular arch where bone formation had been initiated. PMID- 1743431 TI - Induction of tubules in rat metanephrogenic mesenchyme in the absence of an inductive tissue. AB - Differentiation of metanephrogenic mesenchyme to renal tubular epithelium requires induction by the ureteric bud in vivo or any of several embryonic tissues in vitro. In an effort to eliminate the tissue requirement in embryonic induction, extracellular matrices and soluble factors were analyzed individually or in combination for their ability to stimulate tubulogenesis in uninduced metanephrogenic mesenchyme from 13-gestation-day rat embryos. These evaluations have established that pituitary extract and epidermal growth factor (EGF) in concert with a matrix can promote morphogenesis of mesenchymal rudiments in culture. While type I collagen, laminin, or fibronectin matrices all promoted tubulogenesis in the presence of pituitary extract and EGF, type IV collagen proved the most effective. Under these conditions, tubules were induced in 23/24 mesenchymal rudiments by 9 days in culture. Mesenchyme was not induced prior to explanation since it formed no tubules when cultured in a medium that allowed tubulogenesis in intact embryonic kidneys. Preliminary characterization of the undefined factor in pituitary extract was consistent with a protein of molecular weight greater than 100,000 but less than 300,000. When uninduced metanephrogenic mesenchyme from mouse was used instead of rat tissue, a similar pattern of morphogenesis was not observed, suggesting that the described medium is inappropriate for promoting differentiation in mouse or, less likely, that different mechanisms mediate differentiation in rat and mouse. These studies show that embryonic induction can occur in explanted rat renal mesenchyme in an appropriate environment and does not require the presence of an inductive tissue. PMID- 1743432 TI - Stage-related chondrogenic potential of avian mandibular ectomesenchymal cells. AB - We have examined the in vitro stage-related chondrogenic potential of avian mandibular ectomesenchymal cells using micromass cultures. Our results indicate that mandibular ectomesenchymal cells as early as stage 16, soon after the formation of the mandibular arches and well before the initiation of in vivo chondrogenesis, have chondrogenic potential which is expressed in micromass culture. There is an increase in the total area of the cultures occupied by cartilage when cells from increasing stages of development are used. The nodular pattern of chondrogenesis in these cultures indicates that mandibular ectomesenchymal cells are a heterogenous population from the time of mandibular arch formation. In addition, we studied the temporal expression of the genes for extracellular matrix proteins during in vitro chondrogenesis and correlated the morphological changes with the pattern of gene expression. Low levels of type II collagen mRNA are present in the cultures prior to detection of any stainable cartilage matrix and increase 5 fold just before the onset of chondrogenesis in vitro. On the other hand mRNA for cartilage proteoglycan core protein was not detected until the second day of culture when stainable cartilage matrix was present and progressively increased thereafter. Messenger RNA for type I collagen was present at the time of initiation of cultures and continuously increased during the culture period. Our experiments also indicated that embryonic epithelia can inhibit the in vitro chondrogenesis of mandibular ectomesenchymal cells and that the inhibitory effect of embryonic epithelia is independent of its age and site of origin. PMID- 1743433 TI - Trials and tribulations: the cost of developing gene therapies. PMID- 1743434 TI - Harland G. Wood. September 2, 1907 - September 12, 1991. PMID- 1743435 TI - The value of accreditation of animal laboratory care. PMID- 1743436 TI - New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids. AB - In primary cultured adipocytes, metabolic substrates such as glucose and amino acids have profound effects on modulating insulin's stimulatory actions on glucose uptake and protein synthesis. Insights into how substrates modulate insulin action were recently obtained when we discovered that the routing of incoming glucose through the hexosamine biosynthesis pathway leads to a refractory state over a period of several hours in which the ability of insulin to stimulate glucose uptake is severely impaired--a state known as insulin resistance. Glutamine:fructose-6-phosphate amidotransferase was found to play a central role in the development of insulin resistance as this enzyme catalyzes the first and rate-limiting step in the formation of hexosamine products. Collectively, these results are consistent with the idea that the hexosamine biosynthesis pathway serves as a glucose sensor coupled to a negative feedback system that can limit the extent of glucose uptake in response to hyperglycemic and hyperinsulinemic conditions. PMID- 1743437 TI - Corticosteroids, receptors, and the organ-specific functions of 11 beta hydroxysteroid dehydrogenase. AB - Reversible oxidation of the biologically active corticosteroids to the inactive 11-dehydrocorticosteroids is catalyzed by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). The properties of the enzyme based on clinical observations of individuals with defective 11 beta HSD expression, and laboratory studies of the properties and behavior of the enzyme, are consistent with separate 11 beta dehydrogenase and 11-oxoreductase species. However, recombinant enzyme expressed in mammalian cells retain both activities, leading to the conclusion that 11 beta HSD is a unique, reversible enzyme. 11 beta HSD is present in most tissues, but its specific functions in most tissues are unknown. How the enzyme may mediate corticosteroid-receptor interaction is illustrated by studies using kidney, testis, and brain. In kidney, 11 beta HSD prevents glucocorticoids from competing inappropriately with aldosterone for mineralocorticoid receptor (MR). Lack of enzyme in humans due to natural causes or inhibition by pharmacological agents results in maximum activation of MR by glucocorticoids, leading to the clinical symptoms of apparent mineralocorticoid excess. Leydig cells of the testes synthesize testosterone, a process that is suppressed by events initiated by the binding of corticosteroid to glucocorticoid receptors (GR). Depletion of active steroid mediated by 11 beta HSD may initiate testosterone production at puberty and affect testosterone production during adult life, as for example during periods of stress. The heterogeneous distribution of MR and GR in the brain reflects the specific regional effects of glucocorticoids and mineralocorticoids on neural function. Colocalization of 11 beta HSD and corticosteroid receptors in brain may be important in controlling the specificity of corticosteroid interaction with GR and MR. The patterns of 11 beta HSD-steroid-receptor interaction illustrated with these three tissues may provide models applicable to other tissues in which corticosteroid receptors and 11 beta HSD coexist. PMID- 1743438 TI - Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. AB - The biosynthesis of the various types of N-linked oligosaccharide structures involves two series of reactions: 1) the formation of the lipid-linked saccharide precursor, Glc3Man9(GlcNAc)2-pyrophosphoryl-dolichol, by the stepwise addition of GlcNAc, mannose and glucose to dolichyl-P, and 2) the removal of glucose and mannose by membrane-bound glycosidases and the addition of GlcNAc, galactose, sialic acid, and fucose by Golgi-localized glycosyltransferases to produce different complex oligosaccharide structures. For most glycoproteins, the precise role of the carbohydrate is still not known, but specific N-linked oligosaccharide structures are key players in targeting of lysosomal hydrolases to the lysosomes, in the clearance of asialoglycoproteins from the serum, and in some cases of cell:cell adhesion. Furthermore, many glycoproteins have more than one N-linked oligosaccharide, and these oligosaccharides on the same protein frequently have different structures. Thus, one oligosaccharide may be of the high-mannose type whereas another may be a complex chain. One approach to determining the role of specific structures in glycoprotein function is to use inhibitors that block the modification reactions at different steps, causing the cell to produce glycoproteins with altered carbohydrate structures. The function of these glycoproteins can then be assessed. A number of alkaloid-like compounds have been identified that are specific inhibitors of the glucosidases and mannosidases involved in glycoprotein processing. These compounds cause the formation of glycoproteins with glucose-containing high mannose structures, or various high-mannose or hybrid chains, depending on the site of inhibition. These inhibitors have also been useful for studying the processing pathway and for comparing processing enzymes from different organisms. PMID- 1743439 TI - Molecular insights into eukaryotic chemotaxis. AB - Many cells display directed migration toward specific compounds. The best-studied eukaryotic models of chemotaxis are polymorphonuclear leukocytes, which respond to formylated peptides and Dictyostelium amoebas, which respond to extracellular cAMP. In both cell types, chemoattractants bind to surface receptors that contain seven transmembrane domains and interact with G proteins. Some cells, such as fibroblasts, undergo chemotaxis toward compounds whose receptors lack this motif and transmit their signals by other mechanisms. The cytosolic changes elicited by chemoattractants include increased levels of cAMP, cGMP, inositol phosphates, and calcium. These changes are correlated with actin polymerization and other cytoskeletal events that result in preferential extension of pseudopods toward the chemoattractant. Dictyostelium cell lines in which specific genes have been disrupted have demonstrated the necessity of a cAMP receptor (cAR1) and a G protein alpha-subunit (G alpha 2) for responsiveness to cAMP. Other proteins, such as myosin heavy chain and several actin binding proteins, are dispensible although their absence does affect the details of chemotaxis. The disruption of other relevant genes and the genetic reconstitution of chemotaxis in cells lacking crucial proteins should reveal many clues about this complicated and fascinating process. PMID- 1743440 TI - The steroid receptor superfamily: mechanisms of diversity. AB - The steroid receptor superfamily of ligand-dependent transcription factors is characterized by marked conservation of both structure and function between the various receptors. Despite their well-documented extensive similarities, these receptors respond to a diverse range of ligands, which results in an even more impressive diversity of function. A variety of strategies is used at each point in the pathway from ligand binding to gene expression to achieve this diversity. The nature of the ligand is important as are the tissue-specific patterns of receptor gene expression, the presence of binding proteins, and the effects of cell- or tissue-specific ligand-modifying enzymes. Once bound to the receptor, the nature of which may vary as a result of either differential splicing or gene duplication yielding multiple isoforms, the activated receptor may form hetero- or homodimers. A complex interplay then occurs between the receptor dimer, other nuclear proteins, the response element, and the promoter complex to regulate gene expression. These elements may vary as a function of the cell type, other stimuli, and the context and sequence of the response element (or elements) in a given gene. By these mechanisms diversity may even be achieved for a given ligand, receptor subtype, gene, or cell. The observations may help to explain certain phenomena in hormone biology that are difficult to reconcile with the previous, simple, univariant model of steroid hormone action. PMID- 1743441 TI - Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress. AB - A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity. PMID- 1743442 TI - [Myocardial scintigraphy with 99mTc MIBI. The use of a single-day protocol in a multiregional center: a comparison between planar and tomographic imaging]. AB - The use of a single-day protocol for 99mTc MIBI myocardial scintigraphy is particularly well-suited for the nuclear medicine departments that are the referral centres for the cardiology departments of several community hospitals. The aim of the study was to compare, in the same patient population, the diagnostic accuracy of planar and SPECT imaging with 99mTc MIBI using a single day protocol. Thirty-nine patients (31 males and 8 females, age range 32-69 years) were studied because of effort chest pain. Of them, 7 had a pre-test probability of coronary artery disease less than 2.5%; coronary angiography demonstrated significant coronary obstructions in the remaining 32 subjects and 21 of them also had a history of previous myocardial infarction. All patients underwent 99mTc MIBI myocardial scintigraphy with acquisition of planar and SPECT images after injection of a low dose (370 MBq) at rest and after a second higher dose (1110 MBq), injected approximately four hours later during exercise stress testing. The normalcy rate in the 7 patients with low pre-test probability was 100% using both imaging techniques. For the diagnosis of previous infarction, the sensitivities of planar and SPECT images were 71% and 96% respectively. For the diagnosis of effort ischemia the sensitivity values were 34% and 88%, respectively, using planar and SPECT imaging. With regard to the classification of the diseased coronary arteries, the sensitivities of planar and SPECT studies were 42% and 79% respectively, and the related specificities were 91% and 77%. We may conclude that using a single-day protocol planar imaging seems to allow lower levels of diagnostic accuracy both for the diagnosis of effort ischemia and the classification of the diseased vessels as compared to SPECT, which appears therefore in a similar setting the imaging technique of choice. PMID- 1743443 TI - [Changes in the wall motion of left ventricle in dipyridamole-induced ischemic cardiopathy studied by nuclear magnetic resonance. A comparison with myocardial scintigraphy with 99mTc MIBI]. AB - To investigate whether magnetic resonance imaging (NMR) can detect alterations in LV contractility during myocardial ischemia, ten patients aged 32-72 with coronary artery disease underwent ECG gated NMR performed at 0.5 Tesla after intravenous infusion of high dose dipyridamole (DP) (0.7 mg/Kg) over 5 minutes. LV contraction in planes similar to echo short axis projection was imaged under condition, 3' and 15-20' after infusion of DP by fast multiphasic imaging (FMI), multiple angulated cine-NMR sequence with a temporal resolution of 50 m/sec. Entity and size of perfusion defects after DP were determined by Tc 99m MIBI myocardial scintigraphy. In all patients changes in LV contractility appeared at NMR in the same site of perfusion impairments revealed with MIBI. In 8 patients the alterations lasted even more than 20' after the first NMR scan. NMR provides the opportunity of performing long-lasting assessment of ventricular wall contractility and enables to exactly localize the site and extension of kinetic changes as well as their time of onset and time duration. PMID- 1743444 TI - [The diagnostic and prognostic value of echo-dipyridamole in patients with suspected coronary disease: a comparison with the stress test]. AB - The aim of the study was to assess the relative diagnostic and prognostic accuracy of high-dose dipyridamole echocardiography test (DET: 2D-echo monitoring during dipyridamole infusion up to 0.84 mg/kg over 10') vs maximal symptom limited bicycle exercise electrocardiography test (EET) in patients with chest pain addressed to coronary angiography. We initially considered 477 consecutive patients, meeting the following inclusion criteria: 1) history of chest pain; 2) off antianginal therapy; 3) no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction. All patients were submitted to a DET and EET--on different days and in random order--within 1 week of coronary angiography (which was performed independently of test results). DET could not be performed in 32 patients for a poor acoustic window in resting conditions (n = 31) or for asthmatic disease requiring xanthine therapy (n = 1); EET could not be performed in 54 patients for inability to exercise, or resting electrocardiographic abnormalities making the EET interpretable. The overall feasibility was of 445/477 for DET and 423/477 for EET (93 vs 89%, p = ns). Criteria for positivity were: transient regional dyssynergy absent in the baseline examination for DET; ST segment shift greater than .15 m V from baseline for EET. Angiographically assessed coronary artery disease (CAD) was considered present when a luminal reduction greater than or equal to 50% occurred in at least 1 major coronary vessel. There were 135 pts with no significant CAD and 256 with CAD; 137 had single, 70 double, 49 triple and/or left main (15) vessel disease. The specificity was higher in DET vs EET (96 vs 59%, p less than .01). The overall sensitivity of DET was similar to EET (67 vs 69%, p = ns), with no significant differences in the subset with single (56 vs 63%, p = ns), double (74 vs 69%, p = ns) or triple (88 vs 86%, p = ns) vessel disease. Patients were followed-up for 26 +/- 22 (range 1 to 73) months considering only death and myocardial infarction as end-points. A Cox stepwise survival analysis identified the Wall Motion Score Index (an integrated semiquantitative measure of extent and severity of the dyssynergy) at peak dipyridamole as the most powerful prognostic predictor (X2 = 18.5, p less than 0001) of all invasive (number of stenotic coronary vessels, X2 = 5.8, p less than .05) and noninvasive (exercise electrocardiography positivity, p = ns) parameters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1743445 TI - [The prevention of the myocardial toxicity of doxorubicin with superoxide dismutase]. AB - The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD was administered intravenously at the dose of 10,000 U/Kg one minute before and 30 minutes after each DXR administration. Cardiac toxicity was monitored in vivo by means of electrocardiography (QaT interval), by determining the contractile properties of isolated atria, and by light and electron microscopy evaluation of left ventricle fragments excised 5 weeks after the last DXR administration. The degree of morphologic lesions was quantitated according to the score system proposed by E. Billingham. DXR treated rats showed, in comparison with control animals treated with saline a decrease of body weight gain, a progressive and irreversible prolongation of QaT, decrease of contractility of isolated atria, and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain, QaT prolongation and the impairment of myocardial contractility. Moreover morphologic lesions were significantly reduced in rats receiving DXR + SOD. The present data indicate that SOD could represent an important issue in myocardial protection against DXR cardiotoxicity. PMID- 1743446 TI - [The behavior of the arterial pressure at rest and under exertion in normotensive and hypertensive subjects exposed to acute hypoxia at a median altitude]. AB - In order to evaluate blood pressure changes at rest and during effort in response to moderate altitude acute hypoxia, we performed noninvasive blood pressure monitoring and maximal bicycle stress testing in 10 normotensive and 13 untreated mild hypertensive subjects at sea-level and in a mountain resort (m. 2572). Blood pressure was measured every 10 minutes by the Spacelabs 5200 pressurometer and bicycle stress test was performed at initial workload of 50 watts and steps of 50 watts every 3 minutes until exhaustion. Mean systolic blood pressure resulted unchanged in the normotensive subjects (120.8 +/- 10.6 vs 121.5 +/- 6.9 NS) while in the hypertensive ones it increased slightly at 2572 m. (131.0 +/- 12.3 vs 137.0 +/- 13.1 NS). Mean diastolic blood pressure did not increase significantly at 2572 m in either group (respectively from 74.5 +/- 90 to 80.1 +/- 7.9 NS and from 88.3 +/- 10.2 to 94.7 +/- 10.7 NS) even if blood pressure increase was relevant in some hypertensive subjects. During the monitoring, heart rate increased at 2752 m in both groups, even if this difference was significant in the hypertensive group only (respectively 82.8 +/- 11.8 vs 94.3 +/- 13.2 in normotensive subjects-NS-and 88.0 +/- 6.3 vs 104.0 +/- 7.8 in hypertensive subjects-p less than 0.001). During the ergometric test submaximal systolic blood pressure (100 and 150 watts) increased slightly in both groups, but this difference was significant in hypertensive subjects at a workload of 150 watts only (208.3 +/- 18.2 vs 219.3 +/- 19.2 p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743447 TI - [Holter monitoring with a pill-shaped esophageal electrode]. AB - This study analyzes the possibility of using an oesophageal lead in the ambulatory ECG monitoring in order to improve the diagnostic effectiveness of the method by reliable identification of atrial activity. The oesophageal Holter monitoring was performed on 19 patients (pts) (8 F and 11 M, aged 34 to 79 years). These patients posed precise diagnostic problems unsolved by previous conventional Holter recordings. The oesophageal Holter recording was carried out with a Spacelabs recorder, model 90205 with two channels. One electrode was positioned in the standard lead CM5 and the second in the oesophagus using an Esodyn 2 electrode with a dynamic configuration made by C.B-Bioelettronica (Calenzano, Florence). The oesophageal lead was connected with the recorder by filter model EHF-4. The electrode was swallowed by the patient and the best position regulated on the P diphasic deflection of the highest amplitude. The monitoring allowed correct identification of the P wave over a 24-hour period. The arrhythmia which required the oesophageal Holter monitoring was recorded again in 15 of 18 patients examined. In each of these cases it was possible to solve the diagnostic question. The following arrhythmias were found: constant time correlation between the P deflection and the QRS in accordance with a supraventricular tachycardia with intraventricular conduction delay (4 pts); A-V dissociation in accordance with a ventricular tachycardia (2 pts); pause caused by atrioventricular block 2:1 (1 pt), second degree sinus-atrial block (1 pt), blocked premature atrial beats (4 pts); premature ventricular and premature atrial beats with intraventricular conduction delay (3 pts).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743448 TI - [Right atrial isomerism with pulmonary atresia: the angiocardiographic characteristics and pulmonary circulatory patterns]. AB - The patterns of pulmonary circulation were assessed by angiography in a series of 24 patients with right atrial isomerism (asplenia syndrome) and pulmonary atresia. Mean age at catheterization was 21.5 days (range 1 day-11 months). The pulmonary arteries were confluent in 22 cases (91.7%). Eighteen patients (75%) had ductus-dependent pulmonary circulation in presence of confluent pulmonary arteries, similar to cases of pulmonary atresia combined with complex congenital heart disease. The ductus appeared in continuity with the aortic arch, shaping an acute angle with the descending aorta, as in cases of pulmonary atresia with ventricular septal defect. A bilateral ductus was present in 5 cases (20.8%), 3 with confluent and 2 with nonconfluent pulmonary arteries. One patient presented multiple systemic collaterals to the lungs. All the other patients had normal arborization of the pulmonary arteries. Seven patients presented an obstructed total anomalous pulmonary venous connection: 4 in inferior vena cava and 3 in superior vena cava. These anatomical observations provide useful information for the surgical palliation of these anomalies and, probably, warrant pre-operative angiographic evaluation in all the patients with right atrial isomerism. PMID- 1743449 TI - [The diagnosis of pulmonary embolism: the role of noninvasive technics]. AB - Today a large group of patients with pulmonary embolism is still undetected because this disease is not suspected. We evaluated the role of routine clinical procedures such as history, chest x-ray, electrocardiogram and blood gas analysis in the diagnosis of this disease. We studied 177 patients sent to our observation with suspicion of pulmonary embolism, which was later confirmed in 97 and excluded in 80. Prolonged immobilization, surgical procedures and deep vein thrombosis are the most frequent predisposing factors (P less than 0.05 or less) in patients with pulmonary embolism with respect to patients with unconfirmed suspicion of embolism. Among symptoms and signs, pleuritic chest pain, sudden onset of dyspnea, tachypnea, fever, enlarged jugular veins, enhanced pulmonary component of the second heart sound, pulmonary systolic murmur and basal hypophonesis were the most frequent signs (P less than 0.005 or less) in patients with embolism. Among radiographic signs "sausage" descending pulmonary artery, diaphragmatic elevation, pulmonary infarction, Westermark sign and azygos vein enlargement were more frequent (P less than 0.05 or less) in patients with embolism with respect to patients with unconfirmed suspicion of embolism. Among electrocardiographic signs, tachycardia, P-R segment displacement and negative T wave in V1-V2 were more frequent in patients with embolism with respect to patients with unconfirmed suspicion of embolism (P less than 0.05 or less). PO2, standard pO2 and pCO2 were significantly lower (P less than 0.001) in patients with embolism. After discriminant analysis of the whole data set most patients were correctly classified as embolic (90/97) and non-embolic (75/80).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743450 TI - The Framingham Heart Study shows no increases in coronary heart disease rates from cholesterol values of 205 to 264 mg%. PMID- 1743451 TI - [Informatics for cardiology at the ACC '91. Congress of the American College of Cardiology]. PMID- 1743452 TI - Atrioventricular block following therapy with recombinant interleukin 2. PMID- 1743453 TI - [Rosa fresca aulentissima]. PMID- 1743454 TI - [Further comment on the classification of unstable angina]. PMID- 1743455 TI - ANA releases statement on mobilization of nurses. PMID- 1743456 TI - One song: many voices. PMID- 1743457 TI - What do we do when we disagree? PMID- 1743458 TI - Issues of concern to nurse practitioners. PMID- 1743459 TI - Opportunities in gerontological nursing. PMID- 1743461 TI - School health on the move. PMID- 1743460 TI - Should GNA continue to be a union? PMID- 1743462 TI - Taking the mystery out of delegate credentialing. PMID- 1743463 TI - Open letter to Santa. PMID- 1743464 TI - Power Line for women and children. PMID- 1743465 TI - [Counseling in artificial fertilization]. AB - Since 1 October 1990, German legislation requires compulsory counselling of an infertile couple before artificial insemination on the medical and psychosocial aspects, by a doctor not performing the treatment. A prerequisite of successful counselling, which enables the couple to take a decision and helps coping with the psychosocial stress of sterility and its consequences, is, in addition to the intrinsic motivation of the couple, also the empathy and the discussion with the doctor. Subject for counselling should be the burdens of therapy, effects of the sterility upon sexuality, partnership, and communication, motivations for wanting a child and the functions of the child for both partners individually and as a partnership. As a prophylactic measure against the development of a neurotic desire for a child and a fixation upon sterility therapy, alternative resolving strategies for therapy failure should be discussed and developed. PMID- 1743466 TI - [Duration of desire for a child, contraceptive behavior and rate of previous infertility treatment. An epidemiologic study of 750 consecutive patients in labor at the Oldenburg Gynecologic Clinic using a structured interview]. AB - In order to gain current information, on how long a healthy couple desiring a child has to wait until conception, on previous contraceptive behaviour and prior infertility treatment, 750 women were interviewed within 7 days after delivery between January and November, 1989, using a standardised questionnaire. This sample represents one third of all patients, who delivered a child in an Oldenburg hospital during the time period covered. 544 women had desired a pregnancy, an additional 206 women had not directly planned a pregnancy, and 73 of these had taken no precautions against conception, since they were willing to accept a pregnancy if it should occur. 133 women called their pregnancy an "accident", which in 87 couples occurred despite some kind of contraceptive procedure. The absolute number of contraceptive failures was highest for timed intercourse (n = 38) and users of oral contraceptives (n = 32). Couples without a history of infertility treatment had to wait for an average period of 3.4 months before a conception occurred (95% confidence limits: 3.1-3.8 months). The mean age of the women in this group was 28.1 +/- 0.2 years, whereas on an average their male partners were 30.9 +/- 0.2 years of age. The likelihood to achieve pregnancy within the first 4 months of trying, varied between 13 and 15% per month. After 6 months of waiting, the pregnancy rate per cycle was reduced to 6%, whereas, after one year, the likelihood for conception was only 1%. Half of all couples desiring a pregnancy achieved this within 4 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743467 TI - [Pregnancy after direct oocyte-sperm transfer (DOST)--a simple alternative to in vitro fertilization (IVF)]. AB - We report on the first pregnancies achieved at our clinic following direct oocyte sperm-transfer (DOST). Immediately after follicular aspiration, oocytes together with spermatozoa prepared by the swim-up-technique are transferred to the uterus in a manner similar to the embryo transfer following IVF. Our study population consists of 9 patients with bilateral tubal occlusion, accompanied by a male factor in three cases. Up to now, we have achieved four pregnancies, including one twin pregnancy, all occurring, when a male factor was absent. The method described appears promising in terms of efficiency, reduction in the costs and technical procedures during treatment of human infertility. PMID- 1743468 TI - [Prenatal diagnosis with chorionic villi and placenta puncture biopsy in the 1st to 3d trimester of pregnancy: diagnostic value of chromosome studies]. AB - Chorionic villus sampling and placental biopsies became established diagnostic alternatives to amniocentesis worldwide during the 80's. Safety and accuracy are the most important criteria for the evaluation of these newer techniques as compared to amniocentesis. We report on our experience with more than 3400 chromosome analyses between 1985 and 1990 from first to third trimester of pregnancy in a single centre. Most obvious is the higher frequency of mosaicism, which is often, but not always confined to the placenta. Mosaicism accounts for the overwhelming majority of all discrepant (so-called false negative or false positive) cytogenetic findings. The most important prerequisites for diagnostic accuracy of chromosome analyses are meticulous separation of villi immediately after the sampling procedure as well as simultaneous use of direct preparation and cell culture. If mosaicism is not taken as sound evidence for foetal aneuploidy, the accuracy of cytogenetic diagnoses after chorionic villus sampling and placental biopsies is in the same range as the one after amniocentesis. PMID- 1743469 TI - [Bacteriologic findings before and in transcervical chorionic villi biopsy and their clinical relevance]. AB - Between August 1987 and May 1989, bacteriological examinations of smears from the cervical canal was performed in 358 pregnant women, who underwent transcervical sampling of chorionic villi. The outcome of 349 of these pregnancies is documented. 12 of these patients (3.5%) had an artificial abortion for genetic reasons. In 12 other patients, the pregnancy ended before 28 weeks (one child surviving). Microbiological examinations showed that in 187 women (52%), it was possible to culture one or more microorganisms from the cervical canal. The most frequently detected pathogen was Chlamydia trachomatis (111 women, 31%). In pregnancies, where more than one microorganism could be cultured, the risk of following abortion was 8.9 times higher than in those, where no pathogens could be found. In only two of the 12 women with a subsequent spontaneous abortion (16.6%), no microorganism could be found. The bacterial contamination of the cervical canal during TC-CVS seems to be a risk factor for subsequent abortion. Therefore, a bacteriological examination of cervical flora should be performed before as well as during TC-CVS, and antibiotic therapy should be initiated in case of positive results. PMID- 1743470 TI - [Pregnancy with an extremely rare P blood group with anti-PP1Pk]. AB - The authors report on a successful pregnancy in a young Turkish patient with p and anti-PP1Pk-antibodies. Anti-PP1Pk is considered to cause haemolytic diseases in the newborn and habitual abortions. The patient was treated via plasma exchange and substitution with intravenous immunoglobulin. At 31 weeks of gestation the patient underwent Caesarean section due to growth retardation and pathological signs in the fetal CTG. The child has developed well up to two years after the delivery. Based on our data and a review of the literature, the effectiveness of therapy by plasmapheresis and/or immunoglobulin is discussed. PMID- 1743471 TI - [Placental maturity at term and functional placental performance: CTG changes in relation to histologic detection of placental maturation reserves]. AB - Cardiotocography (CTG) is to be considered today's most sensitive monitoring tool for the functional surveillance of placental performance during parturition. 351 cardiotocographically monitored singleton pregnancies were used as patient material for fine tissue examination of the state of maturity of the villi of the relevant placentas. In histological assessment, placental diagnoses are allocated to defined CTG changes; in particular, however, the identification of reserves, capable of maturing (immature intermediate villi in the centres of the placental subdivisions or placentones), is subject to separate scrutiny. The following results emerge clearly: terminal placentas without maturing potentials, prematurely matured placentas and placentas with deficiency of terminal villi, as well as the absence of immature intermediate villi in the centers of the placentones, are connected with a suspected prepathological or pathological CTG assessment. The histological groups have the lowest incidence of the normal oscillatory type and normal oscillatory frequency and have the highest proportion of abnormal CTG assessments according to the Hammacher score. The absence of the identification of potential maturing reserves (immature intermediate villi) is associated with the highest incidence of Caesarean sections (29.8%). These results show, that the physiological maturing potentials (immature intermediate villi) which can be identified up to term are a histological indication towards regular placental performance, even in labour. PMID- 1743472 TI - [Maternal morbidity after abdominal cesarean section in relation to bacterial amniotic fluid colonization and premature rupture of fetal membranes]. AB - At the time of Caesarean section, amniotic fluid was collected transabdominally from 1025 patients. In 990 patients cultures were performed on the amniotic fluid. The incidence of Caesarean section of all patients was 16.1%, the perinatal mortality in all patients 0.61%, in cases of Caesarean section 1.93%. The influence of bacterial colonisation in the amniotic cavity was analyzed with respect to premature ruptured membranes and frequency of vaginal examinations on the maternal post-operative morbidity (wound-seroma and abscess 2.4%, febrile morbidity 17%, urinary tract infection 19%). Bacterial contamination was present in 33.3% of the amniotic fluid or uterine cavity, after ruptured membranes in 44.3%, without ruptured membranes in 23.35%. There is a significant influence of the positive cultured amniotic fluid on the wound healing and on the febrile morbidity, while the urinary tract infection has been not influenced. The bacterial contamination of the amniotic fluid is correlated to the frequency of vaginal examination and the presence of ruptured membranes. The following microbiologic isolates were found in the amniotic fluids: Staphylococcus epidermidis 36.38%, Streptococcus B 12.23%, Streptococcus D 10.3%, Escherichia coli 8.42%, Staphylococcus aureus 7.88%, Peptococci 3.26%, Streptococcus salivarius 2.99%, Bacteroides 2.4%. According to these data, patients with ruptured membranes of an interval of more than 12 hrs and with more than 7 vaginal examinations could be selected for antibiotic prophylaxis to achieve a reduction in febrile morbidity and in wound infection. PMID- 1743473 TI - [Current status of vaginal ultrasound--a worldwide survey]. AB - In the last five years, vaginosonography has become a routine procedure in Obstetrics and Gynaecology. Many obstetricians, gynaecologists, radiologists and ultrasonographers have recognized the advantages of this method. A number of manufacturers of ultrasound equipment offer several types of vaginal probes. Nevertheless, the rapid development of vaginosonography has led to some disadvantages concerning a standardised terminology and image display. In this study we collected data on the current standards of vaginosonography. To gain data on the current use of vaginosonography, we sent out questionnaires to the 1107 departments of Obstetrics/Gynaecology in the FIGO Registry of 1985. In an accompanying letter we asked the chairmen to pass on the questionnaire to the appropriate specialist. The questionnaire was designed to gather information about the personnel performing vaginosonography and such as technique, transducer frequency, position of the patient and image display used. We received 366 responses. Vaginosonographic investigations are performed in 84% of the Obstetrics/Gynaecological University Departments, of which 90% of vaginosonography was performed by an obstetrician or gynaecologist, 5% by a radiologist and 5% by a technician. Predominantly end firing scanners were preferred. The number of electronic and mechanical scanners were nearly identical (55% vs 45%). The preference for a scanner with a narrow (less than 120 degrees) or wide angle (greater than 120 degrees) was very similar (53% vs 47%). More than half of the replies indicated (54%) used a transducer frequency of 5 MHz, 46% preferred scanners with a frequency between 5.5 and 7.5 MHz. In 55%, the gynaecological examination table was considered superior to a flat table.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743474 TI - [Value of vaginal ultrasonography in noninvasive assessment of the endometrium of the postmenopausal uterus]. AB - The endometrial carcinoma shows an increasing incidence and represents today the most frequent malignoma of the female pelvis. Until now all techniques of detection of this carcinoma or its precursors are invasive and thus are not suitable for screening investigations. Vaginosonography, as the first non invasive diagnostic method, now supplies knowledge about the state of the endometrium. At the Gynaecological Department of the University of Homburg/Saar, West Germany, 221 patients had been preoperatively subjected to vaginosonography before they underwent surgery. Sonographical and histological findings corresponded in atrophic endometrium in 82%, in regular, perimenopausal endometrium in 91%, in endometrial polyps and hyperplasia of the endometrium in 56%, and in endometrial carcinoma in 79%. With regard to the detection of endometrial cancer, a specificity of 96%, a sensitivity of 93%, a positive predictive value of 79% and an accuracy of 96% were established. Thus, according to our experience, vaginosonography represents a valid, non-invasive diagnostical method as a suitable instrument for screening the endometrium. PMID- 1743475 TI - [New knowledge concerning hemostatic changes in gestosis and HELLP syndromes for clinical practice]. PMID- 1743476 TI - [Brucellosis-induced granulomatous non-puerperal mastitis--a case report]. AB - An acute manifestation of a chronic brucellosis localised to the female breast is described. A granulomatous mastitis was identified on histological examination. To our knowledge, this is the first reported occurrence of this phenomenon. It is pointed out that it is clinically difficult to distinguish this type of infection from an inflammatory carcinoma of the breast. PMID- 1743477 TI - [Managing a high risk pregnancy after liver transplantation from the obstetrician's point of view. A case report]. AB - We report about a pregnancy and obstetrical management of a patient who had undergone a liver transplantation. Following a normal pregnancy, the newborn was born spontaneously in the 39th week of pregnancy. During the pregnancy the CSA blood levels were controlled frequently as well as the fetal development. An amniocentesis for chromosomal analysis, measurement of AFP blood levels, virus diagnostic and a phase III ultrasound diagnostic were performed. Immediately after delivery the baby was examined carefully by a pediatrician. Management of such a risk pregnancy, after organ transplantation, is possible if there is a close interdisciplinary cooperation between obstetricians, pediatricians, transplant surgeons and internal medicine specialist. PMID- 1743478 TI - [HELLP syndrome--postpartum]. AB - This report is on a 35-year-old II-para (status post-Caesarean Section due to breech presentation, at that time normal pregnancy) progress, who was hospitalized with hypertension and proteinuria during the 40th week of pregnancy. Both symptoms occurred initially three days before hospitalization. Blood pressure was within the high normal range (140/90 mmHg) as a result of medication with Dihydralazine (50 mg/die). After induction of labour with prostaglandin (PGE2), the patient delivered normally, and the highest blood pressure measured was 140/90 mmHg, following a subsequent curettage under general anaesthesia, which had to be performed due to incomplete deliver of the placenta. Two hours post delivery, sudden epigastric pain occurred, followed by nausea and vomiting. Blood chemistry showed the development of a severe post-partal HELLP-Syndrome with acute renal failure. The case demonstrates, that the life threatening picture of the HELLP-Syndrome may develop without preexistent severe hypertension or proteinuria. For this reason a post-delivery screening of blood chemistry should be mandatory in cases of severe epigastric or right-upper-quadrant pain. PMID- 1743479 TI - [Heterologous and autologous breast reconstruction--current status. Report on the 2d Congress of the Society of Reconstructive Surgery in Gynecology 22 to 24 February 1991 in Baden-Baden]. PMID- 1743480 TI - The Gene (H.J. Muller 1947). PMID- 1743481 TI - Control of large chromosomal duplications in Escherichia coli by the mismatch repair system. AB - Excessive recombination between repeated, interspersed, and diverged DNA sequences is a potential source of genomic instability. We have investigated the possibility that a mechanism exists to suppress genetic exchange between these quasi-homologous (homeologous) sequences. We examined the role of the general mismatch repair system of Escherichia coli because previous work has shown that the mismatch repair pathway functions as a barrier to interspecies recombination between E. coli and Salmonella typhimurium. The formation of large duplications by homeologous recombination in E. coli was increased some tenfold by mutations in the mutL and mutS genes that encode the mismatch recognition proteins. These findings indicate that the mismatch recognition proteins act to prevent excessive intrachromosomal exchanges. We conclude that mismatch repair proteins serve as general controllers of the fidelity of genetic inheritance, acting to suppress chromosomal rearrangements as well as point mutations. PMID- 1743482 TI - Genetic and molecular analysis of new female-specific lethal mutations at the gene Sxl of Drosophila melanogaster. AB - We have isolated three female-specific lethal mutations at the gene Sex-lethal (Sxl): Sxlfb, Sxlfc and Sxlfd. We have carried out the complementation analysis between these mutations and other previously reported Sxlf mutations. It is possible to classify the alleles tested in this report into two complementation groups: the bc group defined by Sxlfb, and Sxlfc, and the LS group defined by SxlfLS. The other alleles tested affect both complementation groups albeit with different degrees. Contrary to what happens with mutations at the LS group, mutations at the bc group do not affect sex determination, nor late dosage compensation nor oogenesis. Both Sxlfb and Sxlfc present a DNA insertion of at least 5 kb between position -10 and -11 on the molecular map, within the fourth intron. On the contrary, Sxlfd, a strong mutation affecting all Sxl functions, is not associated to any detectable DNA alteration in Southern blots, so that it seems to be a "point" mutation. In agreement with their phenotypes, both Sxlfc/SxlfLS and Sxlfc homozygous female larvae express only the late Sxl transcripts characteristic of females, while females homozygous for SxlfLS express only the late Sxl transcripts characteristic of males. Moreover, Sxlfc presents a lethal synergistic interaction with mutations at either da or the X:A ratio, two signals that define the initial activity state of Sxl, while SxlfLS do not. These data suggest that the two complementation groups are related to the two sets of early and late Sxl transcripts, which are responsible for the early and late Sxl functions, respectively: Sxlfb and Sxlfc would affect the early functions and SxlfLS would affect the late Sxl functions. PMID- 1743483 TI - The Drosophila Broad-Complex encodes a family of related proteins containing zinc fingers. AB - The Broad-Complex (BR-C) is essential for metamorphosis in Drosophila melanogaster. This locus is coextensive with the 2B5 ecdysone-responsive early puff and is necessary for puffing and transcription of many subsequently activated late genes in the developing salivary gland. Mapping of 31 cDNA clones indicates that approximately 100 kb of the genome is devoted to the synthesis of many BR-C RNAs. Sequence analyses of these cDNA clones show that the BR-C encodes a family of related proteins characterized by a common core amino-terminal domain fused to alternate carboxy domains each containing a pair of zinc fingers. Most proteins also contain domains rich in distinctive amino acids located between the common core and zinc finger regions. BR-C mutant alleles resulting from chromosomal rearrangements at 2B5 are associated with deletions of 5' untranslated sequences, separation of the core coding domain from the downstream zinc finger domains, or a P element insertional disruption of a zinc finger coding sequence. We infer that the BR-C directly regulates late gene expression by specifying the synthesis of a family of proteins with DNA binding potential. PMID- 1743484 TI - Geographic distribution and inheritance of three cytoplasmic incompatibility types in Drosophila simulans. AB - Wolbachia-like microorganisms have been implicated in unidirectional cytoplasmic incompatibility between strains of Drosophila simulans. Reduced egg eclosion occurs when females from uninfected strains (type W) are crossed with males from infected strains (type R). Here we characterize a third incompatibility type (type S) which is also correlated with the presence of Wolbachia-like microorganisms. Despite the fact that the symbionts cannot be morphologically distinguished, we observed complete bidirectional incompatibility between R and S strains. This indicates that the determinants of incompatibility are different in the two infected types. S/W incompatibility is unidirectional and similar to R/W incompatibility. A worldwide survey of D. simulans strains showed that type S incompatibility was found only in insular populations which harbor the mitochondrial type SiI. Both W and R types were found among mainland and island populations harboring the worldwide mitochondrial type SiII. Type S incompatibility could be involved in the reinforcement of the geographical isolation of SiI populations. PMID- 1743485 TI - The lethal(1)TW-6cs mutation of Drosophila melanogaster is a dominant antimorphic allele of nod and is associated with a single base change in the putative ATP binding domain. AB - The l(1)TW-6cs mutation is a cold-sensitive recessive lethal mutation in Drosophila melanogaster, that affects both meiotic and mitotic chromosome segregation. We report the isolation of three revertants of this mutation. All three revert both the meiotic and mitotic effects as well as the cold sensitivity, demonstrating that all three phenotypes are due to a single lesion. We further show that these revertants fail to complement an amorphic allele of the nod (no distributive disjunction) locus, which encodes a kinesin-like protein. These experiments demonstrate that l(1)TW-6cs is an antimorphic allele of nod, and we rename it nodDTW. Sequencing of the nod locus on a nodDTW-bearing chromosome reveals a single base change in the putative ATP-binding region of the motor domain of nod. Recessive, loss-of-function mutations at the nod locus specifically disrupt the segregation of nonexchange chromosomes in female meiosis. We demonstrate that, at 23.5 degrees, the meiotic defects in nodDTW/+ females are similar to those observed in nod/nod females; that is, the segregation of nonexchange chromosomes is abnormal. However, in nodDTW/nodDTW females, or in nodDTW/+ females at 18 degrees, we observe a more severe meiotic defect that apparently affects the segregation of both exchange and nonexchange chromosomes. In addition, nodDTW homozygotes and hemizygous males have previously been shown to exhibit mitotic defects including somatic chromosome breakage and loss. We propose that the defective protein encoded by the nodDTW allele interferes with proper chromosome movement during both meiosis and mitosis, perhaps by binding irreversibly to microtubules. PMID- 1743486 TI - A functional and structural analysis of the Sex combs reduced locus of Drosophila melanogaster. AB - We have undertaken a developmental genetic analysis of the homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster by examining embryonic and adult phenotypes of mutations affecting Scr gene function. Molecular mapping of Scr breakpoint lesions has defined a segment of greater than 70 kb of DNA necessary for proper Scr gene function. This region is split by the fushi tarazu (ftz) gene, with lesions affecting embryonic Scr function molecularly mapping to the region proximal (5') to ftz and those exhibiting polyphasic semilethality predominantly mapping distal (3') to ftz. Gain-of-function mutations are associated with genomic rearrangements and map throughout the Scr locus. Our analysis has revealed that the Scr locus encompasses genetic elements that are responsible for functions in both the embryonic and larval to adult periods of development. From these studies, we conclude that Scr is a complex genetic locus with an extensive regulatory region that directs functions required for normal head and thoracic development in both the embryo and the adult and that the regulation of Scr during these two periods is distinct. PMID- 1743487 TI - A trans-acting regulatory gene that inversely affects the expression of the white, brown and scarlet loci in Drosophila. AB - A trans-acting regulatory gene, Inr-a, that alters the level of expression of the white eye color locus as an inverse function of the number of its functional copies is described. Several independent lines of evidence demonstrate that this regulatory gene interacts with white via the promoter sequences. Among these are the observations that the inverse regulatory effect is conferred to the Adh gene when fused to the white promoter and that cis-regulatory mutants of white fail to respond. The phenotypic response to Inr-a is found in all tissues in which white is expressed, and mutants of the regulator exhibit a recessive lethality during larval periods. Increased white messenger RNA levels in pupal stages are found in Inr-a/+ individuals versus +/+ and a coordinate response is observed for mRNA levels from the brown and scarlet loci. All are structurally related and participate in pigment deposition. These experiments demonstrate that a single regulatory gene can exert an inverse effect on a target structural locus, a situation postulated from segmental aneuploid studies of gene expression and dosage compensation. PMID- 1743488 TI - Use of in vitro mutagenesis to analyze the molecular basis of the difference in Adh expression associated with the allozyme polymorphism in Drosophila melanogaster. AB - In natural populations of Drosophila melanogaster, the alcohol dehydrogenase (Adh) locus is polymorphic for two allozymes, designated Slow and Fast. Fast homozygotes generally have a two- to threefold higher ADH activity level than Slow homozygotes for two reasons: they have a higher concentration of ADH protein and the Fast protein has a higher catalytic efficiency. DNA sequencing studies have shown that the two allozymes generally differ by only a single amino acid at residue 192, which must therefore be the cause of the catalytic efficiency difference. A previous P element-transformation experiment mapped the difference in ADH protein level to a 2.3-kb HpaI/ClaI restriction fragment; which contains all of the Adh coding sequences but excludes all of the 5' flanking region of the distal transcriptional unit. Here we report the results of a site-directed in vitro mutagenesis experiment designed to investigate the effects of the amino acid replacement. This replacement has the expected effect on catalytic efficiency, but there is no detectable effect on the concentration of ADH protein estimated immunologically. This result shows that the average difference in ADH protein level between the allozymic classes is due to linkage disequilibrium between the amino acid replacement and one or more other polymorphisms within the HpaI/ClaI fragment. Sequence analysis of several Fast and Slow alleles suggested that the other polymorphism might be a silent substitution at nucleotide 1443, but another in vitro mutagenesis experiment reported here shows that this is not the case. Therefore, the molecular basis of the difference in ADH protein concentration between the allozymic classes remains an open question. PMID- 1743489 TI - Low nucleotide diversity in man. AB - The nucleotide diversity (pi) in humans is studied by using published cDNA and genomic sequences that have been carefully checked for sequencing accuracy. This measure of genetic variability is defined as the number of nucleotide differences per site between two randomly chosen sequences from a population. A total of more than 75,000 base pairs from 49 loci are compared. The DNA regions studied are the 5' and 3' untranslated regions and the amino acid coding regions. The coding regions are divided into nondegenerate sites (i.e., sites at which all possible changes are nonsynonymous), twofold degenerate sites (i.e., sites at each of which one of the three possible changes is synonymous) and fourfold degenerate sites (i.e., sites at which all three possible changes are synonymous). The pi values estimated are, respectively, 0.03 and 0.04% for the 5' and 3' UT regions, and 0.03, 0.06 and 0.11% for nondegenerate, twofold degenerate and fourfold degenerate sites. Since the highest pi value is only 0.11%, which is about one order of magnitude lower than those in Drosophila populations, the nucleotide diversity in humans is very low. The low diversity is probably due to a relatively small long-term effective population size rather than any severe bottleneck during human evolution. PMID- 1743490 TI - Variance of neutral genetic variances within and between populations for a quantitative character. AB - The variances of genetic variances within and between finite populations were systematically studied using a general multiple allele model with mutation in terms of identity by descent measures. We partitioned the genetic variances into components corresponding to genetic variances and covariances within and between loci. We also analyzed the sampling variance. Both transient and equilibrium results were derived exactly and the results can be used in diverse applications. For the genetic variance within populations, sigma 2 omega, the coefficient of variation can be very well approximated as [formula: see text] for a normal distribution of allelic effects, ignoring recurrent mutation in the absence of linkage, where m is the number of loci, N is the effective population size, theta 1(0) is the initial identity by descent measure of two genes within populations and t is the generation number. The first term is due to genic variance, the second due to linkage disequilibrium, and third due to sampling. In the short term, the variation is predominantly due to linkage disequilibrium and sampling; but in the long term it can be largely due to genic variance. At equilibrium with mutation [formula: see text] where u is the mutation rate. The genetic variance between populations is a parameter. Variance arises only among sample estimates due to finite sampling of populations and individuals. The coefficient of variation for sample gentic variance between populations, sigma 2b, can be generally approximated as [formula: see text] when the number of loci is large where S is the number of sampling populations. PMID- 1743491 TI - Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. AB - We consider the distribution of pairwise sequence differences of mitochondrial DNA or of other nonrecombining portions of the genome in a population that has been of constant size and in a population that has been growing in size exponentially for a long time. We show that, in a population of constant size, the sample distribution of pairwise differences will typically deviate substantially from the geometric distribution expected, because the history of coalescent events in a single sample of genes imposes a substantial correlation on pairwise differences. Consequently, a goodness-of-fit test of observed pairwise differences to the geometric distribution, which assumes that each pairwise comparison is independent, is not a valid test of the hypothesis that the genes were sampled from a panmictic population of constant size. In an exponentially growing population in which the product of the current population size and the growth rate is substantially larger than one, our analytical and simulation results show that most coalescent events occur relatively early and in a restricted range of times. Hence, the "gene tree" will be nearly a "star phylogeny" and the distribution of pairwise differences will be nearly a Poisson distribution. In that case, it is possible to estimate r, the population growth rate, if the mutation rate, mu, and current population size, N0, are assumed known. The estimate of r is the solution to ri/mu = ln(N0r) - gamma, where i is the average pairwise difference and gamma approximately 0.577 is Euler's constant. PMID- 1743492 TI - A source of small repeats in genomic DNA. AB - The processes of spontaneous mutation are known to be influenced by neighboring DNA. Imperfect nearby repeats in the neighboring DNA have been observed to mutate to form perfect repeats. The repeats may be either direct or inverted. Such a mutational process should create perfect direct and inverted repeats in intergenic DNA. A larger than expected number of direct repeats has generally been observed in a wide range of species in both coding and noncoding DNA. Simulations are carried out to determine how this process might influence the repetitive structure of genomic DNA. These simulations show that small repeats created by this kind of a mutational process can explain the excess number of repeats in intergenic DNA. The simulations suggest that this mechanism may be a common cause of mutations, including single-base changes. The influences of the distance between imperfect repeats and of their degree of similarity are investigated. PMID- 1743493 TI - Influence of gene flow and breeding tactics on gene diversity within populations. AB - Expressions describing the accumulation of gene correlations within and among lineages and individuals of a population are derived. The model permits different migration rates by males and females and accounts for various breeding tactics within lineages. The resultant equations enable calculation of the probabilistic quantities for the fixation indices, rates of loss of genetic variation, accumulation of inbreeding, and coefficients of relationship for the population at any generation. All fixation indices were found to attain asymptotic values rapidly despite the consistent loss of genetic variation and accumulation of inbreeding within the population. The time required to attain asymptotic values, however, was prolonged when gene flow among lineages was relatively low (less than 20%). The degree of genetic differentiation among breeding groups, inbreeding coefficients, and gene correlations within lineages were found to be primarily functions of breeding tactics within groups rather than gene flow among groups. Thus, the asymptotic value of S. Wright's island model is not appropriate for describing genetic differences among groups within populations. An alternative solution is provided that under limited conditions will reduce to the original island model. The evolution of polygynous breeding tactics appears to be more favorable for promoting intragroup gene correlations than modification of migration rates. Inbreeding and variance effective sizes are derived for populations that are structured by different migration and breeding tactics. Processes that reduce the inbreeding effective population size result in a concomitant increase in variance effective population size. PMID- 1743494 TI - Genealogy of neutral genes and spreading of selected mutations in a geographically structured population. AB - In a geographically structured population, the interplay among gene migration, genetic drift and natural selection raises intriguing evolutionary problems, but the rigorous mathematical treatment is often very difficult. Therefore several approximate formulas were developed concerning the coalescence process of neutral genes and the fixation process of selected mutations in an island model, and their accuracy was examined by computer simulation. When migration is limited, the coalescence (or divergence) time for sampled neutral genes can be described by the convolution of exponential functions, as in a panmictic population, but it is determined mainly by migration rate and the number of demes from which the sample is taken. This time can be much longer than that in a panmictic population with the same number of breeding individuals. For a selected mutation, the spreading over the entire population was formulated as a birth and death process, in which the fixation probability within a deme plays a key role. With limited amounts of migration, even advantageous mutations take a large number of generations to spread. Furthermore, it is likely that these mutations which are temporarily fixed in some demes may be swamped out again by non-mutant immigrants from other demes unless selection is strong enough. These results are potentially useful for testing quantitatively various hypotheses that have been proposed for the origin of modern human populations. PMID- 1743495 TI - A mathematical model of interference for use in constructing linkage maps from tetrad data. AB - In determining genetic map distances it is necessary to infer crossover frequencies from the ratios of recombinant and parental progeny. To do this accurately, in intervals where multiple crossovers may occur, a mathematical model of chiasma interference must be assumed when mapping in organisms displaying such interference. In Saccharomyces cerevisiae the model most frequently used is that of R.W. Barratt. An alternative to this model is presented. This new model is implemented using a microcomputer and standard numerical methods. It is demonstrated to fit ranked tetrad data from Saccharomyces more closely than the Barratt model and thus generates more accurate estimates of map distances when used with two-point data. A computer program implementing the model has been developed for use in calculating map distances from tetrad data in Saccharomyces. PMID- 1743496 TI - What's in a name? "Mental" or "physical," "psychiatric" or "medical"? PMID- 1743497 TI - A profile of academic medical-psychiatric units. AB - Medical-psychiatric inpatient programs are a relatively recent phenomenon. Although interest in these programs seems widespread, they are still found primarily at academic medical centers. The authors surveyed 11 such academic units. Variations found between their patient populations, milieu, and organization suggest that these programs, in general, are still in an early stage of evolution. It is hoped that these data will provide a descriptive base of how these programs have developed. PMID- 1743498 TI - Organization and development of pediatric medical-psychiatric units. Part I: Administrative, financial, and political issues. AB - The growing literature regarding the development of medical-psychiatric units to facilitate diagnosis and treatment of patients with combined medical and psychiatric disorders is primarily limited to adult populations. Almost no published information is available concerning combined pediatric medical psychiatric units. This article, the first in a two-part series, outlines the organization and development of a child and adolescent medical-psychiatric unit within a pediatric hospital. Various academic, administrative, political, financial, and clinical issues that must be considered during the developmental process are delineated and discussed. The second part of the series will address clinical management issues. PMID- 1743499 TI - The role of SPECT brain imaging in assessing psychopathology in the medically ill. AB - Cerebral single photon emission computed tomography (SPECT), a method of functional brain imaging, measures cerebral blood flow and metabolism. This paper describes the imaging procedure and several cases where cerebral SPECT was of use in the differential diagnosis of medically ill patients who also presented with psychopathology. SPECT patterns in cerebrovascular disease, dementia, focal epilepsy, and AIDS are at present the best described and seem to be the most specific. Often changes in regional cerebral blood flow are seen before structural changes become apparent on CT or MRI. Cerebral SPECT can add valuable diagnostic information in assessing psychopathology in the medically ill and can often lead to changes in treatment. PMID- 1743500 TI - Managing Medicare reimbursement on medical-psychiatry units. AB - Many general hospitals are confronting issues of financial strain precipitated to a large extent by Medicare payment reductions. The viability of psychiatry programs within general hospitals more than ever depends upon some demonstration of their financial as well as clinical contribution. The aim of this study is to review some of the basic parameters governing Part A (hospital) Medicare reimbursement of DRG-exempt general hospital psychiatry units and to provide options for improving their financial viability. There are a number of specific mechanisms involved in managing Medicare cost and reimbursement. Establishing a system for gatekeeping is important because significant control of payor mix and length of stay resides with the unit gatekeeper. Establishing liaison for short stay patients with nursing home papers is important because Medicare pays on a target cost per discharge. The identification of short-stay patients is financially very favorable, and often critical to balance the unavoidable longer stay patients. This paper also discusses how medical-psychiatric units can interface most effectively with medical-surgical units. Finally, there is some discussion of the need to develop pre- and postadmission outpatient medical psychiatric programs. The financial aspects of medical-psychiatry care, if not the increasing scrutiny of managed care, will force further development of such outpatient programs. PMID- 1743501 TI - Psychiatric disorders in two general hospitals: a survey of prevalence and treatment by nonpsychiatrist physicians. AB - This study reports an opinion survey of 211 nonpsychiatrist physicians in two general hospitals who estimated that 16.1% of their patients have psychiatric disorders and that they spent 13.8% of their time in treating the psychiatric components of their patients' illnesses. Physicians indicated that anxiety and psychosomatic and depressive illness were the most frequent psychiatric disorders and that one-third of them would personally treat such disorders without referral to psychiatric consultation. The findings also suggest that adequate undergraduate psychiatric education was associated with increased recognition of psychiatric disorders and more preference for their personal treatment. In addition, it provides a possible explanation for the discrepancy between the high prevalence of psychiatric disorders in general hospital patients and the low referral rate to psychiatric consultation. PMID- 1743502 TI - Child psychiatry consultations to pediatric inpatients: a literature review. AB - While the prevalence of psychiatric disorders in clinical pediatric populations is high, only a few studies have systematically examined child psychiatry consultations to pediatric inpatients. This paper reviews this body of literature and indicates important areas for further study. Some of the studies did not report basic data such as the number of consults, age, sex, or race of referrals, and referral rate. Without such basic data, it is impossible to make adequate comparisons between studies. Several studies did not report economic status or admission diagnosis of the child, psychiatric intervention/treatment on the ward, or psychiatric referral after discharge. Mostly the samples were small, including data on less than 100 inpatient consults. There is a need for greater consistency in the classification of reasons for referral, so that accurate and meaningful comparisons can be made across sites. The examination of psychiatric diagnoses was complicated by the wide range of diagnostic classifications that have been used. Standardization on the DSM-III-R/IV diagnostic system would make for greater comparability between studies. It would be useful in planning for services if future studies included cost as well as efficacy studies with a randomized control group. PMID- 1743503 TI - "Never been done before"--consultative issues in innovative therapies. AB - The transition of a medical or surgical procedure from impossible to standard therapy requires a stage of experimentation, during which research priorities must be balanced with the interests of the patient. This paper examines such a "first case," and the interpersonal and group dynamics that play a part in the choice of a specific patient to be the first to receive that procedure. PMID- 1743504 TI - Regarding treatment of primary care patients with psychiatric disorders. PMID- 1743505 TI - Mania precipitated by prednisone and bromocriptine. PMID- 1743506 TI - The continuing evolution and update of a literature search schema for consultation-liaison psychiatry: 1991. PMID- 1743507 TI - Nucleotide sequence and expression of the algE gene involved in alginate biosynthesis by Pseudomonas aeruginosa. AB - Alginate (Alg), a random polymer of mannuronic acid and glucuronic acid residues, is synthesized and secreted by Pseudomonas aeruginosa primarily during its infection of the lungs of cystic fibrosis patients. The molecular biology and biochemistry of the enzymatic steps leading to the production of the Alg precursor GDP-mannuronic acid have been elucidated, but the mechanism of polymer formation and export of Alg are not understood. We report the nucleotide sequence of a 2.4-kb DNA fragment containing the algE gene, previously designated alg76, encoding the AlgE protein (Mr 54,361) that is believed to be involved in these late steps of Alg biosynthesis. Expression of algE appears to occur from its own promoter. The promoter region contains several direct and inverted repeat sequences and shares structural similarity with promoters of several other alg genes from P. aeruginosa. In addition, the AlgE protein was overproduced from the tac promoter in P. aeruginosa. N-terminal amino acid sequence analysis showed that the polypeptide contains a signal peptide which is cleaved to form the mature protein during AlgE export from the cell cytoplasm. PMID- 1743508 TI - A split zinc-finger protein is required for normal yeast growth. AB - We have identified a gene that, when present in multiple copies, partially inhibits nuclear protein localization in Saccharomyces cerevisiae. This gene encodes a protein that is a unique member of the Cys2His2 zinc-finger family of DNA-binding proteins. It is designated SFP1 for split finger protein because its two zinc-finger domains are separated from one another by 40 amino acids (aa) as opposed to the usual spacing of 7 or 8 aa for Cys2His2 proteins. Disruption of the SFP1 gene results in slow cell growth, with cells having multiple, nucleated buds. PMID- 1743509 TI - Selection of secretory protein-encoding genes by fusion with PHO5 in Saccharomyces cerevisiae. AB - Secretory protein-encoding genes of Saccharomyces cerevisiae have been cloned by a novel procedure that is based on the functional selection of their fusions with acid phosphatase (APase) at the DNA level. DNA fragments that functionally replace the promoter and signal sequence-encoding regions of the PHO5 gene (encoding APase) have been obtained by positive selection from a pool of cloned random DNA fragments. Five unique DNA sequences containing the promoter, and encoding signal sequences have been isolated. We have also isolated the complete gene, SSP120, encoding one of these S. cerevisiae secretory proteins, SSP120. Gene disruption studies have shown that the SSP120 gene is not essential for viability and growth. The SSP120 amino acid (aa) sequence has 13.5% identity with the middle 88-250 aa residues of the chicken glycosylation site-binding protein. However, SSP120 disruption did not affect protein glycosylation in yeast. The present study provides an alternative approach for the isolation of genes encoding secretory proteins, in contrast to classical genetic approaches that require isolation of functionally defective mutations followed by gene isolation by functional complementation. The present procedure should contribute to our understanding of protein sorting by permitting the cloning of genes encoding proteins targeted to different organelles in the secretory pathway. PMID- 1743510 TI - Lignin peroxidase from the basidiomycete Phanerochaete chrysosporium is synthesized as a preproenzyme. AB - The cDNA clone L18 encoding lignin peroxidase LiP2, the most highly expressed LiP isozyme from Phanerochaete chrysosporium strain OGC101, was isolated and sequenced. Comparison of the cDNA sequence with the N-terminal sequence of the mature LiP2 protein isolated from culture medium suggests that the mature protein contains 343 amino acids (aa) and is preceded by a 28-aa leader sequence. In vitro transcription followed by in vitro translation and processing by signal peptidase resulted in cleavage at a site following the Ala21 (counted from the N terminal Met1 of the initial translation product). The resultant protein contains a 7-aa propeptide, indicating that LiP is synthesized as a preproenzyme. PMID- 1743511 TI - pUBEX/pUBSEX: a versatile expression vector system for production of fusion and nonfusion proteins in Escherichia coli. AB - Despite the large number of expression vectors now available, none provide the facility of allowing fusion and nonfusion protein production from the same vector system. In some situations it is preferable to obtain an insoluble fusion protein, in others a soluble nonfusion protein may be required. We have designed, constructed and tested a modification of the pEX vectors, in which it is possible to express the product of a suitably inserted cDNA either as part of a Cro-beta galactosidase (Cro-beta Gal) fusion or as a delta Cro fusion which contains only nine noninsert-encoded amino acids at its N terminus. The conversion from Cro beta Gal to delta Cro fusion protein production is achieved by a simple intramolecular deletion of lacZ sequence from the pUBEX vector, to create the pUBSEX variant. Plasmid pUBEX can be induced to produce large amounts of insoluble Cro-beta Gal fusion proteins, whereas pUBSEX will produce predominantly soluble delta Cro fusion proteins. PMID- 1743512 TI - Identification of a unique specificity determinant of the colicin E3 immunity protein. AB - Plasmid immunity to a nuclease-type colicin is defined by the specific binding of an immunity (or inhibitor) protein, Imm, to the C-terminal nuclease domain, T2A, of the colicin molecule. Whereas most regions of colicin operons exhibit extensive sequence identity, the small plasmid region encoding T2A and Imm is exceptionally varied. Since immunity is essential for the survival of the potentially lethal colicin plasmid (Col), we inferred that T2A and Imm must have co-evolved, retaining their mutual binding specificities. To evaluate this co evolution model for the col and imm genes of ColE3 and ColE6, we attempted to obtain a stabilized clone from a plasmid which had been destabilized with a non cognate immunity gene. A hybrid Col, in which the immE3 gene of the ColE3 was replaced with immE6 from ColE6, was lethal to the host cells upon SOS induction. From among this suicidal cell population, we isolated a stabilized, i.e., evolved, clone which produced colicin E3 (E3) stably and exhibited immunity to E3. This change arose from only a single mutation in ImmE6, from Trp48 to Cys, the same residue as in the ImmE3 sequence. In addition, we constructed a series of chimeric genes through homologous recombination between immE3 and immE6. Characterization of these chimeric immunity genes confirmed the above finding that colicins E3 and E6 are mostly distinguished by only Cys48 of the ImmE3 protein. PMID- 1743513 TI - Cloning and transcriptional analysis of the ADE6 gene of Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae gene, ADE6, encoding 5'-phosphoribosylformyl glycinamidine synthetase (EC 6.3.5.3) has been cloned by complementation of an ade6 auxotroph. Transformation of ade6 mutants with ADE6-carrying centromeric plasmids restored normal, adenine-independent growth behavior in the recipients. Strains containing a disrupted ade6 allele were constructed and behaved as stable adenine auxotrophs. Southern transfer and genetic analyses of strains carrying a disrupted ade6 allele demonstrated that the cloned gene was ADE6 and not a suppressor. The cloned ADE6 DNA was mapped on the RAD2-proximal fragment of chromosome VII by hybridization on yeast chromosomes separated by pulsed-field gel electrophoresis. Northern-blot hybridization experiments show that the ADE6 region produces two different mRNA species of approx. 5 and 2 kb. Disappearance of the larger, but not the smaller, transcript is associated with ade6 mutations. A threefold repression in the amount of the 5-kb ADE6 mRNA is observed when growth medium is supplemented with exogenous adenine. PMID- 1743514 TI - The gene encoding squalene epoxidase from Saccharomyces cerevisiae: cloning and characterization. AB - The gene (ERG1) encoding squalene epoxidase (ERG) from Saccharomyces cerevisiae was cloned. It was isolated from a gene library, prepared from an allylamine resistant (AlR) S. cerevisiae mutant, by screening transformants in a sensitive strain for AlR colonies. The ERG tested in a cell-free extract from one of these transformants proved to be resistant to the Al derivative, terbinafine. From this result, we concluded that the recombinant plasmid in the transformant carried an allelic form of the ERG1 gene. The nucleotide sequence showed the presence of one open reading frame coding for a 55,190-Da peptide of 496 amino acids. Southern hybridization experiments allowed us to localize the ERG1 gene on yeast chromosome 15. PMID- 1743515 TI - Molecular cloning of the Candida maltosa ADE1 gene. AB - The structural gene (ADE1) encoding phosphoribosyl-aminoimidazole succinocarboxamide synthetase (SAICAR synthetase; EC 6.3.2.6) in Candida maltosa has been isolated by functional complementation of an ade1 strain of Saccharomyces cerevisiae. The gene was localized on a 2.5-kb BamHI DNA fragment. Nucleotide sequence analysis of the cloned gene has revealed an open reading frame encoding a protein (SAICAR synthetase) with an Mr of 32,751. The codon bias index, 0.68, indicates that the ADE1 gene is a moderately highly expressed gene. The cloned gene shows 63.5% nt identity and 65.2% deduced amino acid identity with the S. cerevisiae ADE1 gene which encodes the same enzymatic activity. The gene may be used as a convenient genetic marker for construction of a new host vector system for C. maltosa. PMID- 1743516 TI - A bacterial homolog to the mitochondrial enoyl-CoA hydratase. AB - A 257-amino acid (aa) open reading frame in the photosynthetic bacterium, Rhodobacter capsulatus, shows significant homology to the mitochondrial enoyl-CoA hydratase (290 aa). This similarity in size and sequence suggests that R. capsulatus oxidizes fatty acids using specific components, more like the mitochondrial system than the multifunctional component system of Escherichia coli. PMID- 1743517 TI - Nucleotide sequence of the gene encoding yeast C-8 sterol isomerase. AB - The ERG2 gene encoding the Saccharomyces cerevisiae C-8 sterol isomerase, an enzyme involved in plant, animal, and fungal sterol biosynthesis was sequenced. A large open reading frame comprising 222 amino acids was observed. PMID- 1743518 TI - Introduction of single-copy sequences into the chromosome of Escherichia coli: application to gene and operon fusions. AB - We have developed a general method for the introduction of any cloned sequence into the chromosome of Escherichia coli. This method employs an Hfr strain which carries a fragment of bla (the pBR322 gene imparting ampicillin resistance) between lacI and lacZ. Plasmid-borne inserts which are flanked by sequences from bla and lacZ can be introduced at this locus by homologous recombination. The isolation of recombinants is enhanced by selection for transfer of an integrated copy of the plasmid during conjugation. Once introduced into the chromosome, the inserted sequences can be transferred to other strains by conventional methods such as P1 transduction or conjugation. This method is suitable for the transfer of any cloned sequence to the chromosome and is particularly well suited to the construction of chromosomal gene and operon fusions with lacZ. PMID- 1743519 TI - The hydC region contains a multi-cistronic operon (nik) involved in nickel transport in Escherichia coli. AB - We have cloned the multigenic hydC locus of Escherichia coli on a 7.1-kb BamHI EcoRI fragment. Since its gene products are likely to be involved in the specific nickel transport [Wu et al., Mol. Microbiol. 3 (1989) 1709-1718], we propose a new gene designation, nik, to replace hydC. In vivo gene expression studies and complementation analysis support the notion that the nik locus is a multi cistronic operon consisting of two to five genes. The first two genes, arranged in the order nikA and nikB, encode two proteins of 59 and 27.5 kDa, respectively. The downstream genes direct the biosynthesis of three polypeptides of 30, 28 and 25.5 kDa. Southern-blot analysis showed that mutant HYD720 carries a chromosomal deletion of 5.1-kb covering both nikA and nikB, whereas a 0.8-kb deletion in mutant HYD790 includes the sole nikB region. The cloned nik operon and the deletion mutants will aid greatly in the further molecular characterization of the multicomponent-specific transport of nickel in E. coli. PMID- 1743520 TI - A C-terminal deletion in Corynebacterium glutamicum homoserine dehydrogenase abolishes allosteric inhibition by L-threonine. AB - In Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum, homoserine dehydrogenase (HD), the enzyme after the branch point of the threonine/methionine and lysine biosynthetic pathways, is allosterically inhibited by L-threonine. To investigate the regulation of the C. glutamicum HD enzyme by L-threonine, the structural gene, hom, was mutated by UV irradiation of whole cells to obtain a deregulated allele, homdr. L-Threonine inhibits the wild-type (wt) enzyme with a Ki of 0.16 mM. The deregulated enzyme remains 80% active in the presence of 50 mM L-threonine. The homdr gene mutant was isolated and cloned in E. coli. In a C. glutamicum wt host background, but not in E. coli, the cloned homdr gene is genetically unstable. The cloned homdr gene is overexpressed tenfold in C. glutamicum and is active in the presence of over 60 mM L-threonine. Sequence analysis revealed that the homdr mutation is a single nucleotide (G1964) deletion in codon 429 within the hom reading frame. The resulting frame-shift mutation radically alters the structure of the C terminus, resulting in ten amino acid (aa) changes and a deletion of the last 7 aa relative to the wt protein. These observations suggest that the C terminus may be associated with the L-threonine allosteric response. The homdr mutation is unstable and probably deleterious to the cell. This may explain why only one mutation was obtained despite repeated mutagenesis. PMID- 1743521 TI - Sequences of three genes specifying xylanases in Streptomyces lividans. AB - The entire nucleotide (nt) sequences of three genes (xlnA, xlnB and xlnC) of Streptomyces lividans encoding three distinct xylanases (Xln) have been determined. The nt sequences were confirmed by comparing the deduced amino acid (aa) sequences with the ones derived from the N-terminal aa sequences of the mature purified proteins. The N-terminus of the XlnA showed some homology with either the N-termini or the C-termini of eight other Xln and of two exo glucanases. The N-terminus of XlnB is homologous to that of XlnC and to Xln of seven other microorganisms. PMID- 1743522 TI - Juxtaposition of the genes encoding Mycoplasma pneumoniae cytadherence-accessory proteins HMW1 and HMW3. AB - The loss and reacquisition of high-Mr (HMW) proteins, HMW1, 2, 3, 4 and 5, by Mycoplasma pneumoniae correlates with cytadherence phase variation. We are cloning and characterizing the genes encoding HMW1-5 to understand the mechanism regulating their coordinate expression. HMW1 was purified by polyacrylamide-gel electrophoresis. Amino acid (aa) sequence data were obtained from enzymatically generated peptide fragments from HMW1. A degenerate 17-mer probe synthesized based upon the aa sequence of one peptide clearly identified a single 4.75-kb BamHI fragment of M. pneumoniae DNA under stringent hybridization conditions. This fragment was cloned into pUC19 to generate pKV16. Restriction mapping of the 4.75-kb BamHI fragment in pKV16 revealed a possible overlap with the 9.4-kb EcoRI fragment containing the gene encoding protein HMW3. Southern blotting and reciprocal hybridization studies confirmed this overlap, establishing the juxtaposition of the genes encoding HMW1 and HMW3. Finally, physical mapping analysis by probing restriction fragments of M. pneumoniae DNA resolved by pulsed field gel electrophoresis with the cloned genes encoding HMW1 and HMW3 revealed definitively that the hmw locus maps to a 106.8-kb ApaI fragment, rather than a 117.5-kb ApaI fragment, as had been reported previously for hmw3 [Krause and Mawn, J. Bacteriol. 172 (1990) 4790-4797]. PMID- 1743523 TI - A small multigene family encodes the rod-core linker polypeptides of Anabaena sp. PCC7120 phycobilisomes. AB - The cpc operon of Anabaena sp. PCC7120 is shown to encode ten genes: 5'-cpcB-cpcA cpcC-cpcD-cpcE-cpcF- cpcG1-cpcG2-cpcG3-cpcG4-3'. The 3' portion of this operon includes four tandemly repeated genes encoding phycocyanin (PC)-associated, rod core linker polypeptides of the phycobilisomes (PBS). The products of these four genes are most similar at their N termini, and overall are 50-61% identical and 68-76% similar to one another. The four CpcG proteins of Anabaena sp. PCC7120 are 41-47% identical and 62-65% similar to the single CpcG rod-core linker protein in Synechococcus sp. PCC7002. The N-terminal domains of the polypeptides are also more distantly related to the conserved domains of other types of rod-linker polypeptides associated with PC, phycoerythrin, and allophycocyanin (AP). Three of these rod-core linker proteins (CpcG1, CpcG2, and CpcG4) were demonstrated to occur in isolated PBS by N-terminal amino acid sequence analyses. These results indicate that previously proposed models for the PBS of Anabaena sp. are incorrect. It is suggested that the PBS of Anabaena sp. have eight peripheral rods, each of which interacts with the AP of the core via a specific rod-core linker (CpcG) polypeptide. PMID- 1743524 TI - Autopsy: the final peer review. PMID- 1743525 TI - Study: atypical pneumonias not as rare in elderly as believed. PMID- 1743526 TI - Newer joint prostheses offer advantages for arthritic elderly. PMID- 1743527 TI - Healthcare reform: are physicians losing ground? PMID- 1743528 TI - Pneumonia in the elderly: empiric antimicrobial therapy. AB - Pneumonia, the leading cause of death due to infectious disease in the elderly, can be difficult to diagnose in this age group because clinical signs and symptoms are often muted. Without a definitive isolate, the physician must institute empiric therapy with broad-spectrum antibiotics according to the patient's condition and the setting in which the pneumonia developed. The cephalosporins, because of their safety profiles, are often used alone or in combination with other drugs to achieve broad antimicrobial coverage in elderly patients with pneumonia. In general, elderly patients with pneumonia should be hospitalized, although nursing home residents may be managed in the nursing home if adequate staff and resources are available. PMID- 1743529 TI - Diagnosing cognitive dysfunction in the elderly: primary screening tests. AB - The recognition of cognitive disturbances in geriatric patients has important clinical implications for the primary care physician. Commonly seen cognitive dysfunctions include dementia, pseudodementia, delirium, and frontal lobe syndrome; these may be confounded by overlapping depression. The cognitive examination covers such intellectual and behavioral functions as attention, memory, and language. As many psychiatric disorders result from neurologic brain disease, a psychiatric examination is essential. Mental status questionnaires are useful for screening of high-risk populations for dementia and to quantify the degree of cognitive dysfunction for purposes of management planning and surveillance. PMID- 1743530 TI - CPR in the elderly: when should it be performed? AB - Data comparing the success of CPR in elderly hospitalized persons, those living in the community, and those in long-term care facilities show varying results. In general, elderly patients who receive CPR following arrest do not fare as well as younger patients, but there appears to be a subgroup of elderly in whom the success rate is relatively high. Specifically, patients who demonstrate ventricular fibrillation or ventricular tachycardia are more likely to survive than are those demonstrating asystole or electromechanical dissociation. Most studies have not shown a difference in mental or functional impairment between older and younger survivors of cardiac arrest. PMID- 1743531 TI - Benign symptomatic hyperandrogenism in a postmenopausal woman. AB - Hyperandrogenemia in postmenopausal women requires an evaluation to exclude pathologic ovarian or adrenal causes. Our patient exhibited no signs of hypercortisolism, congenital adrenal hyperplasia, or adrenal or ovarian neoplasia based on biochemical testing and pelvic sonography. We hypothesized that unexplained androgen excess in our patient was due to the development of gonadotropin-dependent excess ovarian stromal androgen production. This syndrome may be comparable to gestational hyperreactio luteinalis where elevated gonadotropins stimulate ovarian stromal androgen production. If tumor can confidently be excluded, such women may benefit from gonadotropin suppression with long-acting GnRH-a. PMID- 1743532 TI - Vegetative dysfunction and disease of central nervous system. Italian Society of Neurology Study Group on the Autonomic Nervous System. Proceedings of the 5th workshop, Bari, November 9-10, 1990. PMID- 1743533 TI - Acetylcholine release in experimental autonomic neuropathy. AB - Autonomic neuropathy is a common complication of diabetes. In this study we evaluated autonomic neuropathy by determining somatostatin (S-14)-evoked acetylcholine (Ach) release from postsynaptic parasympathetic fibers in the atria of controls (C) and streptozotocin diabetic rats (STZ-D), with and without tetrodotoxin (TTX). The release induced by S-14 did not differ in C and STZ-D. TTX blocked S-14 induced Ach in C but failed in STZ-D. TTX resistance in STZ-D may be explained by variations of membrane potential in nerve fibers. PMID- 1743534 TI - Urine retention due to intra-spinal cord injection of colchicine in rats: improved recovery of bladder function by monosialoganglioside GM1 and nerve growth factor administration. AB - Intra-spinal cord injection of a low dose of colchicine (2 micrograms/rat) at the lumbar level affects the micturition reflex leading to voiding suppression, bladder hypertrophy and overflow incontinence which lasts about four weeks. The administration of nerve growth factor and monosialoganglioside GM1 normalizes urine output within 3 days and improves recovery of the bladder contraction tested by a cystometric analysis. PMID- 1743535 TI - Vagally-induced non-adrenergic, non-cholinergic inhibitory motility in the rabbit stomach "in vivo". AB - In atropine-treated rabbits, electrical stimulation of vagal nerves at low frequency and low basal gastric volumes evoked a biphasic response: rapid onset relaxation followed by rebound contractions. Increase in the frequency of stimulation and/or in basal gastric volume caused a depression of the rebound contraction and a conversion of the biphasic response into a triphasic one: i.e., the post-stimulus excitatory motility was followed by a long-lasting slow relaxation. The rebound contraction, which was mimicked by arterial injections of prostaglandin E2, appears to be a key factor in the conversion of one type of response into the other. PMID- 1743536 TI - Cardiorespiratory effects evoked by electrical stimulation of somatic afferent fibers. AB - Several neurophysiological studies have shown that electrical activation of afferent fibers of somatic nerves can evoke inhibitory or excitatory cardiovascular responses. The present investigation was undertaken to examine the effects induced by electrical stimulation of somatic nerves on cardiocirculatory and respiratory functions in anesthetized rabbits. Both low frequency stimulation and high frequency stimulation of afferent fibers of somatic nerves caused two distinct patterns of cardiocirculatory and respiratory reflex responses absolutely similar to those observed in our previous experiments on rabbits with dynamic and static exercise. The present findings do not support the existence in the somatic nerves of afferent fibers with cardiorespiratory effect having physiological functions different from that of producing cardiopulmonary adjustments to muscular activity. PMID- 1743537 TI - Heart "timing" versus artery "timing". Neurovegetative effects in compensated and decompensated cardiocirculatory failure. AB - The hypothesis that the main local goal of the neurovegetative cardiovascular regulation is to set and maintain the cardiac cycle and the time constant of the arterial system within a given reciprocal proportion is discussed in this paper. Drastic changes in this reciprocal proportion can induce cardiocirculatory failure. Three different models of cardiocirculatory failure (congestive, hypovolemic and anaphylactic) have been considered in order to test the hypothesis. It is possible to outline a theory that is, decompensated failure occurs at very high levels of sympathoadrenal activation, when the arterial time constant increases when compared to the cardiac cycle, owing to mechanical properties of the arterial wall. PMID- 1743538 TI - Anti-fatigue action exerted by the sympathetic nervous system in the rabbit digastric muscle. AB - Stimulation of the cervical sympathetic trunk, at frequencies within the physiological range, consistently elicits a partial recovery of the contractile force in the fatigued digastric muscle. This action, together with the tension potentiation induced by the sympathetic system in the non-fatigued muscle, could improve the muscular performance under the physiological conditions associated with increase in the sympathetic outflow. PMID- 1743539 TI - Maintained cellular function of adrenal medullary cells in parkinsonian dysautonomia. AB - Adrenal gland involvement in Parkinson's disease was reported by different authors. Further studies became relevant after adrenal was proposed as dopaminergic donor for neurotransplantation. Chromaffin cells were grown in culture and the effects of nerve growth factor (NGF) tested: no differences were observed between parkinsonian and control cells. The expression of the beta-NGF mRNA in the parkinsonian adrenal was analyzed: a specific cDNA was synthesized and a 168 bp portion amplified using PCR. The products were identified and the identity of the fragment was confirmed by sequencing. Quantitative PCR demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings demonstrate the retained functional capacity of the parkinsonian adrenal to respond to NGF and express the beta-NGF mRNA. PMID- 1743540 TI - Sympathetic functions in parkinsonism treated with stereotactic surgery: observations in ten patients. AB - Ipsilateral sympathetic deficits, that is symptoms and signs consistent with a diagnosis of Horner's syndrome, have been described in patients who have undergone thalamotomy for dyskinesia as well as for parkinsonism. The present patient material consists of 10 patients with parkinsonism who had undergone stereotactic surgery. Since anhidrosis and miosis are two integral components of Horner's syndrome, forehead sweating and pupillometric response to sympathicomimetic agents have been investigated in this preliminary work. The tests were carried out a considerable time postoperatively. Sweating was stimulated in two different ways: by body heating and by parenterally administered pilocarpine. OH-amphetamine and phenylephrine (an indirectly and a directly acting sympathicomimetic agent) were used in the pupillometric tests. The results were compared with those obtained in a healthy control group. With the OH-amphetamine test, there were some indications of a changed sympathetic activity on the surgical side. However, when comparing these results with those obtained by the phenylephrine test, the inference seems to be allowable that parkinsonian patients operated in this way (target area: ventro-oral thalamic nuclei (Voa and Vop) and the reticular thalamic nucleus) show no definite sympathetic supersensitivity at the late postoperative stage. Our data suggest that the response pattern of the pupils and the sweat glands may be related to the surgical method used and/or to the interval from operation to investigation. PMID- 1743541 TI - Correlation of cardiovascular autonomic function tests, magnetic resonance brain imaging and clinical features in suspect cases of multiple system atrophy. AB - Nine patients presenting with parkinsonian features and no other clinical abnormalities were studied. These patients were evaluated for dopaminergic responsiveness, for cardiovascular reflex autonomic function, and underwent high field magnetic resonance scan. A 0 to 5 point probability score was used to evaluate the possibility that parkinsonian signs were the presenting symptoms of multiple system atrophy (MSA). Five patients were considered at risk for having MSA: three of them were classified as possible MSA cases (score 2-3), two of them were classified as probable cases of MSA (score 4-5). In patients at risk for MSA, no specific pattern of combination of clinical and laboratory data was found; all patients had different combinations of positive findings. PMID- 1743542 TI - Multisystem evaluation in one case of pure autonomic failure. AB - Pure autonomic failure (PAF) is a rare syndrome characterized by a primitive failure of the autonomic nervous system (ANS). We have studied a 53-year old woman suffering from PAF by using ANS provocative tests investigating the cardiovascular system (standing up test, controlled ventilation, Valsalva manoeuvre, handgrip test, cold pressor test, mental stress test, plasma catecholamine levels), tests investigating the intrinsic ocular innervation (pupil reactivity), and the bladder function (urodynamic tests). Our results have shown abnormalities of all the studied parameters and they have also confirmed that these patients need a multidisciplinary autonomic evaluation to correctly identify the syndrome. PMID- 1743543 TI - Alterations of thermoregulation in Parkinson's disease. AB - Sweating and superficial vasodilator responses were studied in 22 patients suffering from Parkinson's disease in order to evaluate the thermoregulatory function. Sweating was evaluated on different areas of the body with a colorimetric method (Minor's method). The superficial vasodilatation at the level of the face was assessed after oral intake of nitroglycerin by means of telethermography. Sweating and superficial vasodilatation were reduced in parkinsonian patients compared with control subjects. Asymmetries in sweating and superficial vasodilator responses were also observed between the left and right sides of the body in the patients. The decreased heat elimination was more apparent on the symptomatic side in patients with hemiparkinsonism. No relationship was found between the alterations of the thermoregulation and the other clinical features of Parkinson's disease. PMID- 1743544 TI - Relationship between bladder dysfunction and brain MRI in multiple sclerosis. AB - We studied 70 consecutive patients with definite multiple sclerosis (MS) to examine the relationship between magnetic resonance imaging (MRI) cerebral findings and urinary disturbances. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Patients with urinary symptoms exhibited greater overall functional disability. A significant correlation between the presence of midbrain lesions and urinary dysfunctions was found which may indicate an important role of the mesencephalic formation to preserve continence. PMID- 1743545 TI - Analysis of sympathetic skin responses in a group of healthy subjects and in patients affected by sphincter disorders and impotence. AB - Bilateral palmar and plantar sympathetic skin responses (SSRs) to pudendal and median nerves stimulation have been recorded in a population of 10 healthy adult subjects. A group of 11 patients affected by sphincter disorders and/or impotence of neurological origin (diabetic neuropathy, ischaemic myelopathy, myelitis, cauda aequina syndrome) was investigated and results were compared with normal values obtained from the control group. The technique is focused on the vegetative component of innervation and is shown to give complementary information on sympathetic dysfunction, in addition to traditional techniques relating to somatic innervation (electroneurography, electromyography, somatosensory evoked potentials. PMID- 1743546 TI - Twenty-four hours blood pressure and heart rate profiles in diabetics with and without autonomic neuropathy. AB - Previous studies have shown an increased incidence of sudden deaths and lower survival in diabetics with autonomic neuropathy. In hypertensive non diabetic patients a direct correlation has been found between nocturnal blood pressure levels and left ventricular hypertrophy. We have shown in diabetics with autonomic neuropathy a flattening in nocturnal blood pressure reduction and increased 24 hours blood pressure values compared to diabetics without autonomic neuropathy and controls. Our results suggest that abnormalities in 24 hours blood pressure profile might play a role in the increased incidence of cardiovascular morbidity and mortality in diabetics with autonomic neuropathy. PMID- 1743547 TI - Micturition syncopes. AB - Micturition syncope accounts for 8.39% of the total number of syncopes and is prevalent among men in the 50 and 60 year age groups. The cardiovascular vegetative nervous system is unaffected in patients with micturition syncope. Sixty-one percent of patients with micturition syncope also exhibit other kinds of syncope. These patients experience vasovagal reaction during the vegetative activation tests more often than patients exclusively with micturition syncope. PMID- 1743548 TI - Effects of posture, effort and psychophysiological activation on atrio ventricular node and Kent bundle refractoriness. AB - A new protocol is described for non-invasive evaluation of electrophysiological effects of autonomic nervous system on both normal and abnormal atrio-ventricular conduction in patients with Wolff-Parkinson-White (WPW) syndrome. In 64 WPW patients with stable Kent-type ventricular preexcitation transoesophageal atrial pacing has been carried out to quantify changes in both atrioventricular (AV) node and Kent bundle refractoriness and maximal conductive capability induced by posture, physical exercise and psychophysiological activation. A significant shortening of AV nodal and accessory pathway refractory periods was found, induced by manoeuvres enhancing the sympathetic outflow, being the AV node the most sensitive structure. This finding suggests that an exhaustive investigation protocol of WPW patients should include the evaluation of the neurovegetative effects on cardiac electrophysiological parameters, under conditions which can reproduce as close as possible the individual situations a patient has to face in his real life. PMID- 1743549 TI - Plasma tetranectin and ovarian neoplasms. AB - Plasma tetranectin was measured in 67 controls, 121 patients with a benign or malignant ovarian tumor, and 24 patients with another benign gynecologic disease to evaluate the predictive value of plasma tetranectin. A significant reduction of plasma tetranectin was found in every malignant tumor type except for mucinous tumors. Further a significant correlation was found between stage of tumors and plasma tetranectin. Depending on the cutoff level the sensitivity for stage 1 cancer ranged from 52 to 71%. In stage 1 + 2 the sensitivity ranged from 58 to 75% and for advanced cancer (stage 3 + 4) from 80 to 95%. The corresponding specificities ranged from 97 to 84%. Plasma tetranectin may be a useful tool for detecting early stages of ovarian cancer. PMID- 1743550 TI - Rationale for using pathologic tumor dimensions and nodal status to subclassify surgically treated stage IB cervical cancer patients. AB - Between 1969 and 1988, 401 patients were treated by radical hysterectomy and pelvic lymphadenectomy for Stage IB cervical carcinoma at the University of Alabama at Birmingham. In multivariate analysis, pathological tumor diameter (P less than 0.0001) and the presence of lymph node metastasis (P = 0.0005) proved to be the dominant two histopathologic features that significantly correlated with overall survival. Although 5-year survival for the overall group was 85%, 5 year survival in patients with lesions greater than 3.0 cm in diameter and with regional nodal metastasis was less than 30%. This discrepancy in survival in surgically treated early-stage cervical cancer patients supports a need for subcategorization by risk factors such as pathologic tumor dimensions and nodal status and for further investigation of alternative neoadjuvant and adjuvant therapies in those early-stage cervical cancer patients deemed at high risk for poor overall survival. PMID- 1743551 TI - Squamous cell carcinoma of the vulva: prognostic factors influencing survival. AB - One hundred seventy-two cases of patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975 to 1988 are reported. The mean age was 66 years with a range of 21 to 101 years. The distribution by stage included Stage I, 65; Stage II, 44; Stage III, 50; and Stage IV, 13 patients. Groin node dissections performed on 145 patients showed negative nodes, 58%; unilateral positive nodes, 28%; and bilateral positive nodes, 14%. The distribution of patients with positive nodes was influenced by stage: Stage I, 14%; Stage II, 23%; Stage III, 72%; Stage IV, 92%. The overall cumulative 5-year survival was 71% and this was significantly influenced by stage of disease: Stage I, 94%; Stage II, 91%; Stage III, 36%; Stage IV, 26%. Stages I/II and III/IV were combined for analysis. In Stages I/II, survival was significantly influenced by tumor grade while size, patient age, and lymph node status did not influence survival. In Stage III/IV, survival was significantly influenced by tumor size, node status, and number of positive nodes while grade, patient age, and tumor location did not influence survival. Squamous cell cancer of the vulva is effectively treated with radical surgery but advanced-stage disease with regional metastases significantly alters survival. PMID- 1743552 TI - Splenectomy in gynecologic oncology: indications, complications, and technique. AB - Although uncommonly performed in this setting, splenectomy is sometimes indicated in patients with gynecologic malignancies. From January 1970 through March 1989, 45 patients at The University of Texas M.D. Anderson Cancer Center underwent splenectomy during the course of gynecologic laparotomies. All procedures were performed by the gynecology staff and trainees. Twenty-seven patients (60%) had ovarian cancer; endometrial and cervical cancers were present in three patients each. The remaining 11 patients had other diseases. Splenectomy was planned preoperatively in only 9 patients (20%). Thirteen patients (29%) underwent splenectomy because of injury to the spleen. Injury was most commonly due to traction during omentectomy, resulting in capsular laceration. The injury was immediately recognized in 12 patients; 1 patient required reexploration for hemoperitoneum. In 24 patients (53%), splenectomy was performed for tumor reduction. Pathologic examination showed that 11 of 24 patients had capsular involvement by tumor, 7 had parenchymal metastases, and 6 had no direct splenic involvement. Residual tumor following cytoreduction was smaller than 2 cm in 62.5% of patients. Splenectomy is a well-tolerated procedure and the operative approach can be tailored to the clinical situation and distribution of tumor. An attempt should be made to repair splenic injury when tumor involvement is not present. PMID- 1743553 TI - Ifosfamide with mesna in squamous carcinoma of the cervix: phase II results in patients with advanced or recurrent disease. AB - Twenty-four evaluable patients with recurrent or advanced squamous carcinoma of the cervix were treated with ifosfamide (IFX) and mesna every 3 weeks. The initial dose of IFX was 1.5 g/m2 q.d. Days 1-5. Mesna was given by continuous infusion (1.5 g/m2/day Days 1-6). Seventy-four courses of treatment were given to 24 patients. All patients were evaluable for toxicity and response. The median survival was 26 weeks from initiation of chemotherapy. There were 4 complete responders (CR); there was 1 partial responder. The response rate was 20.8% (CI, 4-38%). One CR patient remains in clinical remission 30 months after initiation of therapy. The other 3 responders recurred after a disease-free interval of 8, 12, and 18 weeks. WBC below 3000/mm3 occurred in 19 patients and was life threatening (below 1000/mm3) in 5 patients. One patient had life-threatening hemorrhagic cystitis. Eleven patients developed CNS symptoms during treatment including somnolence, coma, and acute delirium. PMID- 1743554 TI - Cancer of the cervix--old and young, now and then. AB - A study of two 5-year periods, 1960-1964 and 1982-1986, in Queensland is made. Changing patterns of preinvasive and invasive cervical carcinoma in the world literature are discussed. The age of presentation, stage, histology, and results in Queensland for cervical carcinoma are analyzed. There are over 500 patients in each quinquennium. While the total female population has increased 86%, the maximum increase is in patients under 35 years and over 65. There has been a 50% decrease in the incidence of cervical carcinoma, but a doubling under the age of 30. The stage at diagnosis has markedly improved with 88% stage Ib in the young as opposed to 50% formerly. Late-stage disease remains a problem of the aged. The mortality in both time spans increases with age. Histologic patterns show an increase in nonsquamous patterns and increased mortality in the rare patterns. We have no evidence of the emergence of a rapidly progressive carcinoma in the young. Papanicolaou smear and education programs appear to be preventing cervical carcinoma and allowing diagnosis of the disease at an earlier stage and age. This is reflected in a decrease in mortality from 9.6 per 100,000 (1960-1964) to 4 per 100,000 (1982-1986). PMID- 1743555 TI - The inability of Gore-Tex Surgical Membrane to inhibit post-radical pelvic surgery adhesions in the dog model. AB - We investigated the ability of Gore-Tex Surgical Membrane (Gore-SM) to inhibit PRPSA formation in 10 adult female canines undergoing radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and resection of the pelvic/abdominal peritoneum. At the time of surgery, one-half of the pelvic/abdominal peritoneal defect was covered with a tailored single layer of the Gore-SM. The membrane was sutured into place with 3-O Dexon in an interrupted manner. Each animal served as its own internal control. No operative/postoperative deaths or postoperative complications occurred. Four weeks postsurgery, euthanasia was effected, necropsy performed, and adhesions quantified. Adhesion scores for the Gore-SM-covered areas (n = 10; mean score, 2.76 +/- 1.47; median, 2.46) were significantly higher than those for control areas (n = 10; mean score, 1.46 +/- 2.13; median, 1.81; P = 0.01). Adhesions to the Gore-SM occurred at wrinkles in or at the edges of the membrane. In contradistinction to the findings of other investigators using different animal models, the Gore-SM appears to increase PRPSA in this unique model. PMID- 1743556 TI - Etoposide (VP-16), ifosfamide/mesna, and cisplatin chemotherapy for advanced and recurrent carcinoma of the cervix. AB - A Phase II study of VP-16 (etoposide), ifosfamide/mesna, and cisplatin (VIP) in advanced and recurrent carcinoma of the cervix was initiated March 1989. VP-16, 75 mg/m2, ifosfamide, 1.0 g/m2, and cisplatin, 25 mg/m2, were administered intravenously daily for 3 consecutive days, every 28 days to a maximum of six cycles. Fourteen patients were entered on protocol. Eight patients had objective responses, all complete. Response duration ranged from 7+ to 24+ months. The chemotherapy was well-tolerated. Hematologic toxicity was the major toxicity and was manageable. VIP appears to be active in advanced carcinoma of the cervix. PMID- 1743557 TI - Prognostic value of flow cytophotometric DNA content analysis in single treatment stage IB-IIA squamous cell carcinoma of the cervix. AB - DNA content was measured flow cytometrically in archival tissue from 65 single treatment stage IB and IIA squamous cell carcinomas of the cervix with at least 5 years of clinical follow-up. Thirty-five cases were treated exclusively by hysterectomy and thirty exclusively by radiation therapy. Tumors were categorized into four groups on the basis of DNA content and cell cycle distribution. DNA content was measured relative to the position of the first resolvable cell peak. G2/M and S-phase fractions were estimated as percentage of cells with DNA contents greater than or equal to relative position 1.70 and percentage of cells with relative positions between 1.20 and 1.70, respectively. The 40 tumors characterized as either aneuploid or nondemonstrably aneuploid with high S-phase fraction estimate had a 5-year recurrence rate significantly higher than that of the 25 tumors categorized as tetraploid or nondemonstrably aneuploid with low S phase fraction estimate (52 and 4%, respectively; chi 2 = 15.8, P less than 0.001). Similar results were found when radiation and surgically treated tumors were considered independently (chi 2 = 7.95, P less than 0.005 and chi 2 = 5.7, P less than 0.025, respectively). These data suggest that an increased 5-year recurrence rate is associated with both abnormal DNA content and elevated S-phase fraction in stage IB-IIA squamous cell carcinoma of the cervix, and that this relationship is largely independent of treatment method. PMID- 1743558 TI - Is CA-125 monitoring useful in patients with epithelial ovarian carcinoma and preoperative negative CA-125 serum levels? AB - Between December 1983 and December 1988 we examined the postoperative tumor marker development and correlated this to the clinical course of the disease in 56 patients suffering from primary epithelial ovarian carcinoma of International Federation of Gynecology and Obstetrics stages I-III and with a preoperative CA 125 serum level less than or equal to 65 U/ml. In 54% of all cases there was a reduction of more than 50% of the CA-125 serum level within the first 3 months after surgery. Nine out of thirteen patients with progressive disease (69%) showed an increasing CA-125 serum level with a median lead time of 6 months (0-11 months) prior to clinical diagnosis. These preliminary results indicate that the monitoring of cancer patients with CA-125 tumor marker seems to be a useful method of early diagnosis of progressive disease even in patients with preoperative serum levels lower than 65 U/ml. PMID- 1743560 TI - Prognosis of ovarian cancer developing in the residual ovary. AB - Elective oophorectomy at the time of hysterectomy for benign disease in women during their fifth decade is an important issue for both gynecologist and patient. It has been suggested that cancer developing in the residual ovary has a worse prognosis than the national average (L. McGowan, Obstet. Gynecol. 69, 386, 1987). In an effort to corroborate such finding, 36 women with epithelial ovarian cancer developing in the residual ovary after prior hysterectomy were compared to a group of 121 patients with epithelial ovarian cancer and no previous surgery. Analysis was made of age, stage at diagnosis, feasibility of cytoreductive surgery, and survival in both groups. Only age distribution was found to be significantly different between the two groups of patients (P less than 0.001). Neither FIGO staging or quality of cytoreductive surgery showed a statistically significant difference between both groups. At 3 years, 41% of the subjects with cancer in the residual ovary were alive, compared to 42% in the group without previous hysterectomy. The corresponding figures for 5-year survival are 34 and 27%, respectively (P = 0.939). On the basis of our findings we conclude that the overall prognosis for patients with ovarian cancer developing in the residual ovary does not appear to be any worse than that reported for ovarian cancer in general. PMID- 1743559 TI - Phase II trial of high-dose cisplatin with sodium thiosulfate nephroprotection in patients with advanced carcinoma of the uterine cervix previously untreated with chemotherapy. AB - Cisplatin is one of the most active single agents in the treatment of advanced cancer of the cervix. The concurrent administration of the nephroprotective agent, sodium thiosulfate, has enabled exploitation of the therapeutic potential of cisplatin. To explore the role of cisplatin dose intensity in the treatment of patients with cancer of the uterine cervix, patients with persistent/recurrent measurable disease were treated with cisplatin at 200 mg/m2 as a 2-hr infusion with sodium thiosulfate given at 3.3 g/m2 1 hr prior to cisplatin and 6.6 g/m2 during the cisplatin infusion. Treatment was repeated monthly. Due to the known cumulative toxicity of cisplatin, treatment beyond two cycles (400 mg/m2) was given only to those patients who had at least demonstrated a PR. Audiologic evaluation was done prior to each cycle of treatment. Eleven patients were entered with a median age of 43 years (range, 25-57), a median KPS of 80% (range, 60-90%), and nine epidermoid and two adenocarcinoma, and all patients had received previous pelvic irradiation. Twenty-eight cycles of treatment were given: 1, five cycles; 3, three cycles; 7, two cycles. No greater than or equal to 3+ hematologic, neurologic, or renal toxicity was demonstrated. Ototoxicity was demonstrated in the mild to moderate hearing loss range (3000-8000 Hz). The greatest threshold shift occurred after the first course of cisplatin. There were three PRs with a maximum duration of 4 months. Due to the significant toxicities encountered, the low response rate, and the limited duration of responses, this trial was closed early to accrual. PMID- 1743561 TI - Clear cell adenocarcinoma of the vagina: a second primary in a diethylstilbestrol exposed woman? AB - A clear cell adenocarcinoma of the vaginal remnant in a diethylstilbestrol (DES) exposed woman developed 20 years after anterior exenteration for a histologically similar stage II vaginal cancer. Arguments favoring a new primary cancer over a late recurrence are presented. This case probably represents the first report of a second primary vaginal clear cell cancer after DES exposure in utero. The implications of a second vaginal primary and the need for long-term surveillance in DES-exposed women are discussed. PMID- 1743562 TI - Correction of incontinent ileocolic urostomy with Kock's nipple valve. AB - Continent urostomy procedures may be replacing the incontinent ileal or colon conduit as the preferred method of urinary diversion in gynecologic cancer patients. One method of continent urinary diversion utilizes the detubularized ascending and transverse colon as a reservoir with a tapered segment of distal ileum as the stoma through which the patient catheterizes the pouch (Miami pouch). Failures of this procedure have been reported. A case report of such a failure is presented. This patient was managed by replacing the tapered ileal stoma with a Kock intussuscepted nipple valve made from proximal ileum. The patient is now continent. This technique warrants further investigation as a method of treating patients with continent urostomies of various types (Kock, Indiana, Miami, Mainz) that become partially or completely incontinent. PMID- 1743563 TI - Ovarian cancer. PMID- 1743564 TI - Ultrasound screening for familial ovarian cancer. AB - We have used transvaginal ultrasonography to screen 776 asymptomatic women for familial ovarian cancer. Every woman had at least one first- or second-degree relative develop the disease (677, 87%; and 98, 13%, respectively). The mean age of the study population was 51 years (range, 24 to 78 years); 52% were premenopausal, 36% were naturally postmenopausal, and 12% had undergone a hysterectomy. Overall, 43 women (5.5%) were referred for surgical investigation and 39 had a laparatomy. Nineteen/thirty-nine (48%) had bilateral ovarian masses, and 15% of abnormal ovaries had more than one type of histopathology. Twenty three tumors and thirty-two tumor-like conditions were detected. There were 3 cases of primary ovarian cancer (prevalence, 3.9/1000), all FIGO stage Ia. None of the women has developed ovarian cancer within the first year of the scan (giving a provisional detection rate of 100%). The false positive rate was 40/773 (5.2%), the predictive value of a positive screen result was 7.7%, and the odds in favor of finding any mass at laparotomy were about 19 to 1 or for any tumor, 1 to 1. At surgery the odds against finding primary ovarian cancer were 12 to 1. The positive predictive value of the screening procedure and the prevalence of the disease were significantly higher than the corresponding values from a previous population-based screening program. PMID- 1743565 TI - The effects of early removal of indwelling urinary catheter after radical hysterectomy. AB - Radical hysterectomy has long been a primary mode of therapy for selected gynecologic malignancies. The lower urinary tract is an area associated with complications following this procedure. Lack of satisfactory reflex micturition and urinary retention, diminished bladder sensation, infection, and fistula formation are common adverse sequelae. Prolonged indwelling catheterization is a cornerstone of postoperative management after radical hysterectomy. An alternative regimen consisting of early postoperative catheter removal, with a strict voiding schedule, and intermittent self-catheterization (ISC) for postvoid residuals (PVR) was prospectively investigated. Intermittent self-catheterization was initiated only if the PVR 12 hr after catheter removal was greater than 75 ml. Twenty-six patients who underwent radical hysterectomy were studied. Catheters were removed between the fifth and ninth postoperative day. Eighteen patients (69%) had PVRs less than 75 ml at 12 hr and were successfully managed with a strict voiding schedule only. Eight patients (31%) had 12-hr PVRs greater than 75 ml and were managed with a strict voiding schedule and ISC until the PVR was less than 75 ml for two consecutive voids. These patients were evaluated with fluorourodynamics and none had an abnormal study. Compared to 25 historical control patients, study group median indwelling catheter duration was less (6.0 days compared to 30.0 days) with no increase in postoperative complications. On the basis of these data, early removal of indwelling urinary catheters after radical hysterectomy appears to be an acceptable alternative to long-term catheterization. PMID- 1743566 TI - [Genital bleeding in childhood and adolescence]. PMID- 1743567 TI - [The development of puberty and gonadal function following administration of cytostatic agents in childhood]. PMID- 1743568 TI - [Diagnostic and surgical pelviscopy in children and adolescents]. PMID- 1743569 TI - [Experiencing menstruation]. PMID- 1743570 TI - [Contraception in adolescents]. PMID- 1743571 TI - [Sterilization of mentally retarded girls]. PMID- 1743572 TI - [The value of ultrasonography in pediatric and adolescent gynecology]. PMID- 1743573 TI - [Ultrasonographic assessment of tumors of the adnexa in childhood]. PMID- 1743574 TI - [Evaluation of gynecological diseases according to the law for severely handicapped]. PMID- 1743575 TI - [Medical rehabilitation for the prevention of occupational and employment disability based on gynecologic diseases]. PMID- 1743576 TI - [Stress in the life of a woman]. PMID- 1743577 TI - [Limits to work load of women in occupational life]. PMID- 1743578 TI - [Fatal peritoneal mesothelioma disease in women caused by asbestos exposure at the work place]. PMID- 1743579 TI - [MPEL levels and pregnancy]. PMID- 1743580 TI - [Maternal welfare at the work place and work disability during pregnancy]. PMID- 1743581 TI - [Effect of gainful employment on pregnancy]. PMID- 1743582 TI - [Pregnancy-caused employment prohibition or disease-caused work disability: procedures by gynecologists in the provision of doctors' certificates]. PMID- 1743583 TI - [Work at the display screen and pregnancy]. PMID- 1743584 TI - [Risk of exposure to chemicals in pregnancy]. PMID- 1743585 TI - [Pregnancy and anesthesia]. PMID- 1743586 TI - [Embolizing leg and pelvic vein thrombosis in late pregnancy: indication for simultaneous interdisciplinary procedures]. PMID- 1743587 TI - [Antepartum CTG (II)]. PMID- 1743588 TI - [Diagnosis of infection in at risk pregnancies]. PMID- 1743589 TI - The effect of low affinity platelet factor 4 (LAPF4) secreted by human megakaryoblastic cell line (MEG-01) upon human bone marrow fibroblasts. AB - BACKGROUND: The role of low affinity platelet factor 4 (LAPF4) in the hemopoietic microenvironment has not yet been clarified. METHODS: Low affinity platelet factor 4 (LAPF4) was purified from normal human platelets and the culture medium of the human megakaryoblastic cell line (MEG-01), and their effects upon the growth of human bone marrow fibroblasts were assessed in order to investigate the biological role of LAPF4. The purified LAPF4 was added to the culture media of human bone marrow fibroblasts up to the concentration of 200 ng/m1, and the growth rate of fibroblasts and the uptake of 3H-thymidine into fibroblasts were measured. RESULTS: The molecular weight of LAPF4 from MEG-01 was approximately 8,800, which corresponded to the monomer type of LAPF4 from normal platelets. The density of fibroblasts after 10 days of culture was 4.6 +/- 0.9 x 10(5)/ml, 7.8 +/- 0.8 x 10(5)/ml and 11.3 +/- 0.6 x 10(5) in control medium, in the medium with LAPF4 from platelets and in the medium with LAPF4 from MEG-01, respectively, which indicates that LAPF4 from MEG-01 enhanced the growth rate of bone marrow fibroblast almost 2.5 times. The uptake of 3H-thymidine into fibroblasts was significantly increased by 1,000 ng/ml of LAPF4 from MEG-01. CONCLUSIONS: These results suggest that LAPF4 may play a role in the proliferation of fibroblasts. PMID- 1743590 TI - Non-Hodgkin's lymphoma in the elderly: the impact of advanced age on therapeutic options and clinical results. AB - BACKGROUND: Treatment of older patients with non-Hodgkin's lymphoma (NHL) is difficult and conflicting. Lower responsiveness to therapy has been reported; however, the high risk of treatment morbidity, drug-dose reduction, and the occurrence of unrelated deaths might account for the poor outcome of NHL in the elderly. METHODS: We retrospectively analyzed the therapeutic approach and the outcome in 90 NHL patients aged 65 years or older. Histologic classification was according to the Working Formulation. RESULTS: Twenty-nine patients with low grade NHL have been managed conventionally: complete response (CR) rate was 34.5% and median overall survival was 35 months. Sixty-one patients with intermediate grade (IG, 36 cases) or high-grade (HG, 25 cases) NHL were treated as follows: 5 stage I-IE cases underwent radiation therapy; of 56 stage II-IV patients, 14 had conservative single-agent therapy and 32 received an attenuated CVP regimen. Only 10 patients were considered suitable for attenuated CHOP or CHOP-like programs. Overall CR rate was 50% for IG and 32% for HG NHL: Median survival was 33 months and 10 months (p less than or equal to 0.05), respectively. For IG and HG patients, the attainment of CR influenced survival significantly. Treatment morbidity was observed in 41% of patients. Resistant lymphoma was the major cause of death (31/36) during the first six months of therapy. CONCLUSIONS: In our experience, the outcome of elderly NHL patients treated with conservative therapeutic approaches is poor. Intensive chemotherapy regimens tailored to individual patients are needed to improve clinical results. PMID- 1743591 TI - A regimen for antithrombin III substitution in patients with acute lymphoblastic leukemia under treatment with L-asparaginase. AB - BACKGROUND AND METHODS: Seventeen adult patients with acute lymphoblastic leukemia (ALL) treated with L-asparaginase (20,000 IU/m2 on six alternate days) were infused with antithrombin III (AT III) concentrates (Kybernin P, Behring). Substitution therapy was aimed at increasing the reduced AT III concentration usually found in these patients, since AT III deficiency is thought to be associated with an increased risk of thrombosis. Two schedules of AT III administration, different in dosage, timing and duration were evaluated. The first 7 patients (group A) received a fixed dose of 2,000 U every day for 6 times, starting with the second L-asparaginase (L-ase) infusion, independently of their plasma AT III levels. In the following 10 patients (group B), 20-25 U/Kg b.w. were administered daily for 7 times only when the plasma AT III level was lower than 60% with plasma fibrinogen higher than 100 mg/dl and platelet count higher than 50 x 10(9)/l, or when AT III was below 40%. Thirteen patients who received L-ase without AT III substitution served as controls. RESULTS AND CONCLUSIONS: Both substitution regimens resulted in mean plasma AT III nadir values significantly (p less than 00.1) higher than in the controls. Our data suggest that, in ALL patients receiving L-ase according to the L20 protocol, satisfactory plasma AT III levels may be assured with infusions of 20-25 U/Kg b.w./day for 7-10 days, starting by day 2 of L-ase treatment. PMID- 1743592 TI - Hybrid phenotypes and lineage promiscuity in acute leukemia. AB - Clinical data indicate that AL are heterogeneous diseases with variable responsiveness to chemotherapeutic agents. Based on this evidence, the efforts of most investigators are aimed at providing rapid identification of AL features predictive of distinct prognostic outcomes. A considerable number of reagents (including MoAb and molecular probes) available from commercial sources has been widely used for diagnostic purpose, leading to the identification of "inappropriate" antigen expression and to diagnoses of "mixed" AL (M-AL). The latter still lacks adequate definition and identification criteria, but is frequently reported as a novel entity associated with poor clinical outcome. The use of more accurate methodologic approaches, as well as a better elucidation of normal hemopoietic cell characteristics suggest that true M-AL occur quite rarely: the features of normal precursor counterparts are more frequently conserved. "Ectopic" marker expression, however, which should not be interpreted as reflecting lineage infidelity, may in some instances explain different clinical courses in AL patients. Further elucidation of normal stem cell features, and adequate standardization of AL immunophenotyping--to be performed under proper technical conditions--are needed for a better evaluation of M-AL, both in terms of diagnosis and classification, as well as regarding their clinical significance. PMID- 1743593 TI - Immunohistochemistry of malignant lymphomas. Advantages and limitations of the new monoclonal antibodies working in paraffin sections. AB - On the basis of the experience derived from the study of 2,000 biopsies, the authors critically review the problem of the newly generated monoclonal antibodies (mAbs) working in paraffin sections. The reliability and drawbacks of the most commonly used reagents are examined, with special reference to their employment in the diagnosis of malignant lymphomas. The authors underline that only a few mAbs are really specific, since most reagents give rise to a certain number of cross-reactivities. In the light of this, a wide panel of antibodies should always be applied in the diagnosis of lymphoid tumours in order to avoid possible misinterpretations, which can actually lead to wrong therapeutical decisions. PMID- 1743594 TI - Clinicopathological evolution and multilineage involvement in erythroleukemia: report of a case. AB - Results of sequential chromosome and cytologic studies in a patient with erythroleukemia (EL) by FAB criteria are described here. Major karyotype aberrations (MAKA) as well as normal karyotypes were detected at presentation, when the patient showed erythroid hyperplasia with moderate leftward shift of erythropoiesis and trilineage myelodysplasia, a picture suggestive of multilineage involvement. Following conventional induction therapy, the patient entered a myelodysplastic phase (MDS) with the features of refractory anemia with excess of blasts and subsequently relapsed with classical EL with maturation arrest of erythroblasts. Chromosome studies revealed a 46, XY karyotype in the MDS phase and only MAKA at leukemia relapse. These findings provide further evidence of a multistep cytogenetic and clinicopathological evolution of EL. Concomitant cytogenetic and morphologic studies in this patient seem to suggest the presence of chromosomally abnormal erythroblasts and confirm the existence of a association between MAKA and maturation arrest of erythroblasts. PMID- 1743595 TI - Recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF) in cyclic neutropenia. AB - We describe the case of a 12-year-old boy affected by cyclic neutropenia, at high risk of developing life-threatening infections, treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The drug was effective in reducing the severity of neutropenia and infectious complications in our patient. It was administered for brief periods of time, in contrast to the daily continuous administration reported for rHuG-CSF. Therefore, more extensive studies must be performed to identify the most effective time schedule for the drug. In vitro studies of hemopoietic progenitor cells were useful, in this case, to predict treatment response. PMID- 1743596 TI - Disseminated histiocytosis with undetermined Langerhans' cells simulating an acute non lymphoid leukemia. AB - The authors report on a case of disseminated Langerhans' cell histiocytosis with a clinical presentation and a bone marrow simulating, at onset, an acute leukemia non lymphoid. A hepatic needle biopsy performed for the progressive enlargement of the liver oriented the diagnosis towards a Langerhans' cell histiocytosis. The morphological, immunohistochemical and ultrastructural study of these cells showed them to be undetermined, i.e. Langerhans' cell precursors. PMID- 1743597 TI - Trigeminal neuropathy in a case of mesenteric localized Castleman's disease. AB - Peripheral neuropathy of the limbs has so far been observed in very few patients with localized Castleman's disease, generally of the plasma-cell type. In the present case report, of a plasmacellular type localized within the mesenterium, a 25-year-old woman exhibited a clinical picture of right trigeminal neuropathy (together with more common constitutional symptoms and laboratory findings), which promptly disappeared after surgical removal of the mesenteric mass. To our knowledge, a similar impairment of cranial nerves, and specifically of the trigeminal, has never been reported in patients with the localized form of Castleman's disease. PMID- 1743598 TI - Selective metaphasic blockade of erythroblasts in the bone marrow of patients treated sequentially with recombinant human erythropoietin and vincristine. AB - In the course of a phase I-II clinical study exploring the therapeutic potential of recombinant human erythropoietin in malignancy-associated anemias, a significant morphologic aspect was found in the marrow aspirates in two cases. The first was a patient with Hodgkin's disease, and the other a patient with acute T lymphoblastic leukemia. Bone marrow aspirates were performed while the patients were receiving recombinant human erythropoietin (rHu-EPO), 24 hours after the administration of vincristine, which was part of the therapeutic regimens. In all myeloaspirates over 90% of the numerous erythroblasts were in metaphasic arrest or displayed all the other aspects of so-called C mitoses, including star and ball metaphases, scattered chromosomes and multinuclear cells expressing so-called reconstructive polyproidism. All these alterations are caused by vincristine, a vinca dimer alkaloid, binding mechanistically to tubulin and thus blocking the polymerizing process that forms the mitotic spindle. The target cells for erythropoietin are specifically responsive cells, including microscopically identifiable erythroblasts. This is the first morphological demonstration in man of the combined effects of erythropoietin as a mitogen and vincristine as a mitotic blocker. PMID- 1743599 TI - Centella Asiatica Triterpenic Fraction (CATTF) reduces the number of circulating endothelial cells in subjects with post phlebitic syndrome. AB - Here we report a study performed in order to assess the number of circulating endothelial cells (EC) in normal subjects and in patients with postphlebitic syndrome (PPS), and the effect of treatment with Centella Asiatica Triterpenic Fraction (CATTF), a drug which has been demonstrated to be effective in promoting wound healing in vivo. EC counts were determined by means of differential centrifugation and phase contrast microscopy. Patients with PPS showed an increased number of circulating EC in comparison to normal subjects (3.8 +/- 1.2 cells versus 1.5 +/- 0.6 per counting chamber). Treatment for three weeks with CATTF caused a statistically significant reduction of circulating EC (1.80 +/- 0.6 cells per counting chamber). PMID- 1743600 TI - Fluconazole for disseminated Cryptococcosis in a patient with Hodgkin's disease. PMID- 1743601 TI - [The implication of stimulus-evoked ATP release from neuronal and extraneuronal sites]. AB - Characteristics of the ATP release from non-neuronal tissues were reviewed in connection with that from neuronal tissues. alpha 1-Adrenoceptor and M3 cholinoceptor stimulation produced a postjunctional ATP release from smooth muscles such as the vas deferens and ileal longitudinal muscles of the guinea pig, suggesting the existence of a coupling mechanism between the stimulation of the receptor for the transmitter and postjunctional ATP release. Accompanied with positive inotropic action, cardiotonics elicit postjunctional ATP release, which is derived from mitochondria, in atrial muscles, whereas these drugs are incapable of producing the release from papillary muscles. Possible physiological roles of ATP released to synapses from nonneuronal tissues are considered as follows: 1) the nucleotide may act as an opener of Ca2+ and K+ channels, 2) ATP in the synapse seems to serve as a transsynaptic neuromodulator after conversion to adenosine. PMID- 1743602 TI - [Pharmacological effects and metabolism of extracellular ATP]. AB - Cells are equipped with complex mechanisms for synthesis of ATP and try to keep the intracellular level of this compound, which is indispensable for maintenance of normal function and integrity, as constant as possible. Thus, it is generally believed that ATP rarely cross the plasma membrane of viable cells. However, since the first report of Holton in 1959, the release of nucleotides from cells has become an established fact, and the physiological role and metabolism of the released ATP has become an important topic; potent actions of extracellular purine nucleotides and nucleosides have been recognized for many years. In 1972, Burnstock demonstrated that ATP has a transmitter role in certain types of nerves and proposed a concept of purinergic nerve. The receptor for purine nucleotides, designated as P2, as opposed to P1, by Burnstock in 1978 was further subclassified in 1985 into P2X and P2Y by himself, and we now have a train of P2 receptors, such as P2S, P2T, P2Z and so forth. In this review, I summarized the characteristics of these purinoceptors. Pharmacological effects and metabolism of extracellular nucleotides were discussed and a brief mention was made of ecto nucleotidases. PMID- 1743603 TI - Natural foods and their ecological implications for Macaca thibetana at Mount Emei, China. AB - Natural food plants of partly provisioned groups of Macaca thibetana included about 196 species belonging to 135 genera and 72 families. The macaques consumed mainly bamboo shoots and fruits for about 2 months in autumn, whereas they relied on active or passive provisions from visitors, a variety of structural parts of plants and a small amount of invertebrates in late spring and summer and ate mainly mature leaves and bark for the rest of the year. About half of the species eaten came from the dense herb and shrub layers. This forest-dwelling species shows a distinctive feeding and foraging pattern in comparison with other macaques, explaining why M. thibetana has the largest body weight of all macaques. PMID- 1743604 TI - Colonic adenocarcinoma and hepatic myelolipomas in a Goeldi's monkey (Callimico goeldii). PMID- 1743605 TI - [Latex allergies in occupations and everyday living]. PMID- 1743606 TI - [Insulin injection aid. Experiences with its use in Type II diabetes patients]. AB - This article reports on the experience gained with an insulin injection aid for use by type II diabetics. The baseline data provided by a questionnaire survey are discussed in detail. The "pen" proved simple to use and was readily accepted. A number of shortcomings were identified and improvements suggested. The significantly superior metabolic control observed in patients using such aids is briefly discussed. In addition, detailed consideration is given to the models presently available and desirable future prospects are identified. PMID- 1743607 TI - [Psychosocial changes following cardiopulmonary resuscitation]. PMID- 1743608 TI - [Digital luminescence radiography . 2: Technical implementation and clinical application--future developments]. AB - In the previously published Part 1 of this paper the basic principle of digital luminescence radiography (DLR) was presented and the technical implementation of the data acquisition system with its advantages and disadvantages as compared with conventional radiography were described [3]. Part 2 covers processing, display, archiving and communication of image data; in addition, suggestions for future improvements in the technique are made. Image processing research is directed towards optimal presentation of the detected data by spatial frequency filtering with unsharp masking and by gradation enhancement. Additional information can be acquired by means of dual energy investigations. The image is displayed on either monitor or transparent X-ray film. Picture archiving requires large storage capacities, and picture communication needs fast transfer rates. At present, about 450 installations for digital luminescence radiography are in clinical use worldwide. Routine use can be expected when technical improvements have been implemented. PMID- 1743609 TI - [Interactions with anabolic steroids]. PMID- 1743610 TI - [Treatment of moderate and severe pain. Ketorolac--a new analgesic]. AB - Overall, the studies available to date show that ketorolac is a powerful analgesic with no action on the central nervous system and a long-lasting effect of rapid onset. The analgesic effectiveness of ketorolac in the treatment of moderate to severe pain, is comparable with that of 10-12 mg of morphine, 100 mg of pethidine, or 30 mg of pentazocine. However, ketorolac, an inhibitor of prostaglandin synthesis, is not subject to the strict regulations of the narcotic drugs law. On account of its favorable adverse reactions profile, ketorolac is particularly well suited for the treatment of postoperative pain. Further major indications are pain associated with trauma to bones and muscles, as also cancer related pain, in which area, a "saving effect" on simultaneously employed opiates and opioids can be achieved. PMID- 1743611 TI - Effects of glucagon-like peptide 1 (7-36) amide and glucagon on amylin release from perfused rat pancreas. AB - The effects of glucagon-like peptide 1 (7-36) amide [GLP-1 (7-36) amide] and glucagon on the release of islet amyloid polypeptide (IAPP), or amylin, from the isolated perfused rat pancreas were studied. In the presence of 5.6 mM glucose, GLP-1 (7-36) amide and glucagon stimulated the release of amylin from the perfused pancreas. The infusion of GLP-1 (7-36) amide at a concentration of 10( 9) M elicited a biphasic release of amylin similar to that of insulin. The cumulative output of amylin induced by 10(-9)M GLP-1 (7-36) amide was significantly higher than that by 10(-9)M glucagon (p less than 0.01). The amylin/insulin molar ratios induced by GLP-1 (7-36) amide and glucagon were about 1% and did not differ significantly. These findings suggest that GLP-1 (7-36) amide and glucagon stimulate the release of amylin from the pancreas and that the concomitant secretion of amylin and insulin might contribute to glucose homeostasis. PMID- 1743612 TI - Kinetic studies on hepatic handling of glucagon using the model of non recirculating perfused rat livers. AB - Using the model of the in vitro non-recirculating perfused rat liver we studied kinetic aspects of the hepatic handling of glucagon. Under conditions of a 20 min glucagon infusion (glucagon mass flows of 0.05, 0.46 and 4.75 ng/g liver/min, respectively) according to a rectangular profile both total and individual glucagon extractions were dependent on mass flow and time. The time course of glucagon extraction started with an acute phase within the first minute of infusion with a maximum value of 70%, which decreased within the following 30 sec by more than 40%. Depending on concentration, there was a progressive decrease in the hepatic extraction of glucagon up to the end of perfusion. Hepatic glucagon degradation was found to take place only at a little extent. Immediately after terminating the hormone infusion, the liver changed over into a glucagon releasing organ. Kinetics of glucagon infusion and glucagon-induced hepatic glycogenolysis did not distinguish by parallelism but rather by phase shifting. PMID- 1743613 TI - Polyamine influences on the prolactin stimulation of phosphoprotein synthesis in hydroxyurea synchronized MCF-7 human mammary epithelial cells. AB - The actions of prolactin on the rate of synthesis of an isoelectrically precipitable (pH 4.6) phosphoprotein fraction of the MCF-7 human mammary epithelial cell line were determined in cells synchronized at the G1:S interphase of the cell cycle employing hydroxyurea in a serum-free defined medium. Cells not allowed to enter the S-phase of DNA replication, by maintaining hydroxyurea in the incubation medium, exhibited an increased rate of [3H] leucine incorporation into the isoelectrically precipitable phosphoprotein fraction when exposed to prolactin and 1-5 mM spermidine. Cells released from the hydroxyurea induced synchrony exhibited an increased rate of [3H] leucine incorporation in response to prolactin when ornithine, putrescine, or spermidine were present. The polyamine spermine was ineffective in allowing prolactin's action on phosphoprotein synthesis. In synchronized cells released from the hydroxyurea block, prolactin was shown to effect an increased rate of phosphoprotein synthesis at the posttranscriptional G1 stage of the cell cycle. All prolactin responses were attained with physiological concentrations of the hormone. During and subsequent to the synchrony period with hydroxyurea, the presence or absence of insulin was found to be useful for the "staging" of the cell cycle to maintain cell synchrony and obtain prolactin effects on phosphoprotein synthesis. PMID- 1743614 TI - Triiodothyronine control of ATP-citrate lyase and malic enzyme during differentiation of a murine preadipocyte cell line. AB - In the Ob 17 preadipocyte cell line, during adipose differentiation, T3 amplified the progressive expression of two enzymes of the lipogenic pathway, ATP-citrate lyase (ATP-CL) and malic enzyme (ME) as previously described for fatty acid synthase (FAS) and fatty acid synthesis, and in the same time-period of development. However, the stimulation by T3 was sustained at late stages of differentiation whereas it declined in FAS studies. The stimulation was preceded by an increase in the relative abundance of the specific mRNAs. Two ME mRNA species were detected (21S and 27S) and found to be differently distributed. Their abundance was asynchronously increased by T3 with a predominant effect on the 21S species. Culture of the cells in a thyroid-hormone depleted medium prevented any significant increase of ME activity. Early inclusion of T3 largely restored ME development whereas late elimination of T3 only moderately impaired it. It is suggested that T3 plays a crucial role at an early step of adipose differentiation, this leading to an increased expression of a set of late adipose phenotypes such as several lipogenic enzymes. PMID- 1743615 TI - Serotonin content of the interscapular brown adipose tissue of growing rats. AB - In brown fat of newborn rats the serotonin (5HT) content is high during the first five days of life. This may play a part in the lipid repletion of the tissue, lipids being the main fuel for nonshivering thermogenesis. Subsequently 5HT increases more in young rats reared at 16 degrees C than in those reared at 28 degrees C but to a lesser extent than norepinephrine (NE) content. A possible role of 5HT in thermoregulation of the rat during the early postnatal period is discussed. PMID- 1743616 TI - HGH20k species and variability of GH responses to long-duration exercise in male cyclists fed different food supplements. AB - Exercise studies dealing with hGH have always considered this hormone as a unique molecular entity. We postulated that the well-known variability in blood total hGH response could possibly be explained, at least in part, by concomitant changes in blood hGH20k levels, variant form possibly expressing some of the hGH anti-insulinic properties. Six male trained cyclists were imposed a 2-hr long ergocycle exercise. Food supplements were given prior to and/or during exertion to exacerbate a possible contribution from hGH20k to total hGH variability by modification of substrate availability. Both blood total hGH and hGH20k levels increased with exercise, the largest increases being observed in absence of supplementation. Large variability of responses were observed in both blood total hGH and hGH20k levels, the latter variant contributing minimally to total blood hGH response (4.3 +/- 0.8%), and being closely associated with the main species (r = 0.90; p less than 0.001). It was concluded that variations associated with hGH20k increases observed in response to prolonged exercise cannot explain the large intra-and inter-individual variability measured in blood total hGH response. PMID- 1743617 TI - Serum manganese-superoxide dismutase in patients with diabetes mellitus and thyroid dysfunction as judged by an ELISA. PMID- 1743618 TI - Diurnal variation of leucyl aminopeptidase activity in the rat hypothalamus. PMID- 1743619 TI - Thermal and nutritional influences on cardiac muscle 3,5,3'-triiodothyronine nuclear receptors. PMID- 1743620 TI - Effect of ovarian follicular fluid peptide (OFFP) on FSH and EGF binding to granulosa cells. PMID- 1743621 TI - Evidence for liver epinephrine. PMID- 1743622 TI - Phase II trial of ifosfamide and mesna in previously treated patients with non Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. AB - Ifosfamide (1.25 g/m2 intravenously/day x 5) with mesna (20 per cent of the ifosfamide dose x six doses on each day of ifosfamide therapy) was administered to 46 previously treated patients with non-Hodgkin's lymphoma of which 31 were eligible and evaluable. A 29 per cent response rate (9/31) was observed (two CR and seven PR) with a median duration of response of 2.5 months. Myelosuppression was dose-limiting. Hemorrhagic cystitis was observed in three patients (10 per cent). Nausea and vomiting was generally mild or moderate. One patient developed transient neurotoxic symptoms with confusion and disorientation. An additional patient developed an anaphylactic-type reaction with shortness of breath and respiratory stridor during the fourth course of therapy. Ifosfamide, as a single agent, produces remissions of limited duration in non-Hodgkin's lymphoma in patients in second or third relapse. PMID- 1743623 TI - Toxicity and preliminary results with a new eight-drug regimen (CEOP-IMVP-DEXA) in the treatment of aggressive lymphomas. AB - A combination of two non-cross-resistant regimens, CEOP and IMVP-Dexa given every 4 weeks, three to six times according to response was tested in patients with untreated histological proven high and intermediate grade non-Hodgkin's lymphoma. To date eight Austrian centres entered 37 patients in this multicentre trial. Data are available from 33 patients, three were excluded, two because of pretreatment, one because of wrong histology. Twenty-five patients are evaluable for response, 21 had a complete and three a partial remission, two of them entered a complete remission after radiotherapy to residual disease, resulting in a complete remission rate of 92 per cent. Only one patient progressed during therapy. Until now three patients relapsed after achieving a remission. Observation time is 0.4-23.8 months, median 8.8 months. Toxicity was primarily hematologic with 53.3 per cent of patients having granulocyte nadirs below 0.5 x 10(9)/L and 3.3 per cent below 0.1 x 10(9)/L. Although 60 per cent of patients had infections, there was only one life-threatening infection in an AIDS patient. CEOP-IMVP-Dexa can be safely given even in smaller hematologic centres and is able to achieve a high rate of complete responses in patients with high and intermediate grade malignant non-Hodgkin's lymphomas. PMID- 1743624 TI - Sequential versus alternating chemotherapy for high grade non-Hodgkin's lymphomas: a randomized multicentre trial. AB - In a multicentre phase III trial 146 previously untreated patients with high grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either four cycles of CHOEP (cyclophosphamide 750 mg/m2 iv d 1, doxorubicin 50 mg/m2 iv d 1, vincristine 2 mg iv d 1, etoposide 100 mg/m2 iv d 3-5, prednisolone 100 mg po d 1 5) (treatment arm A), or four cycles of chemotherapy with hCHOP (cyclophosphamide 1200 mg/m2 iv d 1, doxorubicin 40 mg/m2 iv d 1 + 2, vincristine 2 mg iv d 1, prednisolone 100 mg po d 1-5) alternating with IVEP (ifosfamide 1500 mg/m2 iv d 1 5, vindesine 3 mg/m2 iv d 1, etoposide 120 mg/m2 iv d 3-5, prednisolone 100 mg po d 1-5) (treatment arm B). After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 124/146 patients (86 per cent) with 87 per cent CR in arm A versus 83 per cent CR in arm B. During a median follow-up of 17 months (range 2-40) 30 patients relapsed (16 patients arm A, 14 patients arm B). The overall survival at 40 months is projected to be 71 per cent versus 70 per cent for arm A and B, respectively. Disease-free survival is projected to be 68 per cent in arm A and 59 per cent in arm B at 40 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743625 TI - Ifosfamide continuous infusion plus etoposide in the treatment of elderly patients with aggressive lymphoma: a phase II study. AB - A prospective phase II study was performed to evaluate efficacy and toxicity of continuous infusion ifosfamide plus etoposide combination in elderly patients (older than 70 years) with intermediate or high grade non Hodgkin's lymphoma. Chemotherapy was administered with mesna in order to avoid hemorrhagic cystitis. The 21 patients included were either unable to receive the usual front-line chemotherapy given in our institution or relapsing after or not responding to conventional chemotherapy. Only one out of 97 courses of chemotherapy was followed by serious complication consisting in non-lethal pneumonitis. Four out of seven previously untreated patients and five patients treated in first relapse achieved complete response (75 per cent). Out of nine refractory or previously multi-treated patients, only one achieved complete response. We conclude that combination of continuous infusion ifosfamide plus etoposide deserves to be evaluated on a larger scale so that the optimum doses and schedule may be defined. PMID- 1743626 TI - Twin-track studies of ifosfamide and mitoxantrone (I-M) in recurrent high grade non-Hodgkin's lymphoma and Hodgkin's disease. Yorkshire Regional Lymphoma and Central Lymphoma Groups. AB - Fifty-seven patients, initially diagnosed as having advanced high grade non Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I-M) is of value in relapsed patients, especially where options are limited because of previous multi-drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation. PMID- 1743627 TI - IMVP-16 followed by high dose chemotherapy and autologous bone marrow transplantation as salvage treatment for malignant lymphoma. AB - Thirty patients with high-grade malignant lymphoma were treated with ifosfamide VP16213-methotrexate (IMVP-16) combination chemotherapy after failing to respond completely or after relapsing on CHOP-like therapy. Responders to the salvage therapy subsequently were treated with ablative chemotherapy (BCNU, VP16213, Ara C and melphalan) and autografted. Of these 30 patients 11 were in relapse, 11 were partial responders and eight failed CHOP-like therapy. There were eight complete remissions and 12 partial responses to IMVP-16. These 20 patients were transplanted, together with one nonresponder. Ten of these 21 patients are disease-free survivors 16 to 76 months (median 32) after autografting. There were three treatment-related deaths: one before and two during the autografting procedure. Using one of the best salvage therapy combinations followed by high dose chemotherapy and autografting is feasible. The results of this study suggest that an appreciable number of patients may be cured by this procedure. PMID- 1743628 TI - VIM3-ARA C: an effective salvage regimen in refractory or recurrent aggressive non Hodgkin's lymphoma. A report on 18 cases. AB - Based on encouraging results of previous combination regimens, we used a combination of VM26, ifosfamide, methyl GAG, mitoxantrone (or adriamycin), high dose (HD) methotrexate and HD Ara C to treat 18 patients with relapsed or refractory NHL. Front-line therapy had been in most of them a reinforced CHOP regimen. Twelve patients (67 per cent) responded: there were nine (50 per cent) partial responses (PR) and three (17 per cent) complete remissions (CR). Nine of these 12 responders were grafted (eight autologous, one allogeneic transplants), one relapsed before autograft could be performed and the two remaining patients were excluded from autograft because of positive bone marrow. Five of nine patients remained free of disease after 11+ to 27+ months. Response rate was higher in patients who relapsed 'off' therapy (2/3), but CR was also obtained in two refractory NHL and persisted for 11+ and 26+ months, suggesting that VIM3-ARA C was, at least partially, non-cross-resistant with front-line adriamycin containing regimens. PMID- 1743629 TI - Ifosfamide in the treatment of high-grade recurrent non-Hodgkin's lymphomas. AB - We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic, we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours. PMID- 1743630 TI - Pediatric non-Hodgkin's lymphoma abdominal presentations: a comparative study between two treatment regimens at the National Cancer Institute Cairo. AB - Abdominal presentations of pediatric NHL are rarely amenable to complete surgical resection. Chemotherapy is the hallmark of treatment for pediatric NHL. Treatment of various types of this disease including intra-abdominal NHL in children with various protocols have not exceeded 54 per cent two-year disease-free survival. We have attempted to study and compare the effects of two treatment regimen upon two groups of previously untreated children up to the age of 16 years who presented to the Pediatric Oncology Unit at the NCI. The first group included 18 children who presented between 1983 and 1985 and were treated by a modified St Jude regimen: while the second group of patients was comprised of 19 children who presented between 1985 and 1987 and were treated by a multi-national protocol: the MCP 842. The two groups will be compared with respect to various patient characteristics, response to therapy and their two-year disease-free survival as well as overall survival. PMID- 1743631 TI - Prolonged disease-free survival in pediatric non-Hodgkin's lymphoma using ifosfamide-containing combination chemotherapy. AB - Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival. PMID- 1743632 TI - Victims' services in community mental health centers. PMID- 1743633 TI - Social work takes active role in health care reform. PMID- 1743634 TI - Oppositional defiant disorder and conduct disorder. PMID- 1743635 TI - Do benzodiazepines cause depression? PMID- 1743636 TI - Combined therapy for a 30-year-old woman with early-onset dysthymia. PMID- 1743637 TI - Residential programs for persons with severe mental illness: a nationwide survey of state-affiliated agencies. AB - About 1,500 agencies responded to a nationwide survey of community residential programs affiliated with state departments of mental health that was conducted in 1986-87. The agencies served more than 59,000 individuals who had psychiatric disabilities in more than 16,000 residential settings. The results reveal rapid growth in the number of programs since 1980 and the availability of a broad range of residential programs. Group homes and supervised apartments were the most common types of residential programs identified in the survey. The most commonly offered services were social and recreational activities, medication supervision, and on-site crisis intervention. Programs also offered such services as client advocacy and case management. Most program staff did not have professional training in a mental health field. PMID- 1743638 TI - States' strategies for promoting supported housing for persons with psychiatric disabilities. AB - Survey data were used to analyze state government efforts to promote supported housing for persons with psychiatric disabilities in five states--Ohio, Oregon, Rhode Island, Washington, and Wisconsin. States worked to increase mental health service consumers' access to affordable housing by increasing the number of state staff who address housing issues, by developing housing units, and by increasing consumers' income. Legislative mandates and financial incentives were used to encourage service providers to offer more flexible support services. States promoted consumers' involvement in the mental health system by encouraging their participation in state-level decision making and by providing financial support to consumer organizations. PMID- 1743639 TI - A ten-year perspective on three models of sheltered care. AB - Data from three surveys of California sheltered care residents and facilities were used to determine which of three models best describes the use of sheltered care by residents and the provision of services to residents between 1973 and 1983. The continuum-of-care model emphasizes a person's movement along a treatment continuum to greater independence. In the residual model, the focus is on providing habitation for a chronic population from the era before deinstitutionalization. The developmental model emphasizes providing long-term care to persons who seek supported living arrangements at a particular point in their life cycle. Results indicated that the developmental model best describes the way residents used sheltered care, while service provision was based on the continuum-of-care model. In light of these findings, it should be determined whether service provision reflects the actual needs of this population. PMID- 1743640 TI - Effects of sheltered care environments and resident characteristics on the development of social networks. AB - Two hundred and thirty-four members of a 1973 sample of sheltered care residents, three-fourths of whom had schizophrenic disorders, were followed up between 1983 and 1985 to examine the role of supportive and of transitional, high-expectation sheltered care environments in the development of residents' social networks. The influences of revolving-door treatment experiences, psychopathology, and institutionalization were taken into account. The results showed that supportive rather than transitional, high-expectation environments contributed to the development of emotionally and instrumentally supportive social networks. Higher levels of psychopathology and a history of institutionalization resulted in the absence of certain support relationships. Surprisingly, revolving-door treatment experiences were related to positive support and social network outcomes. PMID- 1743641 TI - Factors affecting SSI support for sheltered care residents with serious mental illness. AB - The complexity of Supplemental Security Income (SSI) regulations and procedures allegedly inhibits eligible persons with serious mental illness from obtaining and retaining support. This study examined factors affecting continued SSI support among 393 sheltered care residents with serious mental illness ten years after an initial positive eligibility determination. At follow-up between 1983 and 1985 of 225 cohort members, 182 were receiving SSI benefits, 28 were eligible for SSI due to their low income but were not receiving benefits, and 15 were income-ineligible. The financially needy were most likely to receive SSI support for longer periods of time, and the most severely disturbed spent the least amount of time on SSI. Income-eligible nonrecipients were likely to be young, transient patients using emergency room services as opposed to receiving outpatient counseling. PMID- 1743642 TI - Attitudes of sheltered care residents toward others with mental illness. AB - The social acceptance expressed by 234 former mental patients and by the general public toward persons with serious mental illness was compared. Factors that may affect social acceptance of such persons, including personal characteristics and experiences that promote identification with mentally ill persons and the subject's level of psychological distress, were examined. Former patients expressed attitudes that were much more accepting than those of the general public. As hypothesized, individual characteristics and experiences likely to increase former patients' identification with their peers (that is, visible deviant appearance, a high level of involvement within the sheltered care community, and the experience of negative community reactions to a resident's facility) were related to a higher score on a Guttman scale of social acceptance. An increased level of self-reported psychological distress tended to moderate such supportive attitudes. PMID- 1743643 TI - Short-term group interventions for mentally ill young adults living in a community residence and their families. AB - Data from 12 families of chronic mentally ill young adults who were living in a supportive residential facility were used to compare the effects on family functioning of a multiple-family psychoeducational group and a multiple-family support group. The psychoeducational group provided information about mental illness and family dynamics and taught effective communication and conflict management skills. The support group consisted of unstructured discussions about topics raised by the families. Both groups met once a week for five weeks and included both parents and their mentally ill adult children. The emotional climate, level of organization, and other aspects of the family environment were assessed before and after treatment and at three-month follow-up. Both groups helped families to become more cohesive, to manage conflict more effectively, and to obtain a greater internal locus of control. PMID- 1743644 TI - Comparison of outcomes for clients seeking and assigned to supported housing services. AB - As part of state-supported interventions to reduce risk of rehospitalization, seriously disabled psychiatric patients who had been involuntarily hospitalized twice in the previous three years were assigned to receive supported housing services in an Oregon community. Compared with 22 voluntary clients in the same supported housing program, the 21 involuntary (assigned) clients rated higher on risk factors such as history of suicide attempts, self-neglect, homelessness, and medication noncompliance, The involuntary clients showed a much higher utilization of supported housing services and case management, psychiatric, and shelter services during the nine months after entry into the program, and they had a higher one-year rehospitalization rate. However, they used substantially fewer inpatient days in the six months after entry in the program than in the six months before. PMID- 1743645 TI - Creating a supportive environment using staff psychoeducation in a supervised residence. AB - The prevailing approach to rehabilitation in residential care emphasizes goal attainment. This approach often produces considerable stress for residents, most of whom have schizophrenia. Based on the view that low-demand environments, incorporating graduated expectations, may be more appropriate for this patient population, a three-component model for creating and maintaining a calm, supportive environment in a supervised residence was developed. The model utilizes staff psychoeducation, which is based on the principles of family psychoeducation, a highly effective intervention for patients with schizophrenia. The three components of the model are training in supportive interaction, a medication-monitoring program, and a behavioral approach to problem solving. Resident groups promote each of these components. The groups' goals are encouragement of positive, low-key interactions, compliance with medications, and slow, steady rehabilitation. PMID- 1743646 TI - Awards presented to exemplary state-university collaborations in California, Kentucky, and Pennsylvania. PMID- 1743647 TI - Parkinson's disease, depression, and chronic pain. PMID- 1743648 TI - A system for improving psychiatric record keeping. PMID- 1743649 TI - Readmission patterns of frequent users of inpatient psychiatric services. PMID- 1743650 TI - Psychiatric inpatients' knowledge of their rights. PMID- 1743651 TI - Power and governance issues in general hospital psychiatry. PMID- 1743652 TI - HIV seroconversion. PMID- 1743653 TI - State hospitals in the 1950s. PMID- 1743654 TI - Hypersalivation and clozapine. PMID- 1743655 TI - Clinical training funds can help promote needed change. PMID- 1743656 TI - Perspectives on work and rehabilitation. PMID- 1743657 TI - Refining the concept of dysthymia. PMID- 1743658 TI - Inpatient treatment of adolescents with psychiatric and substance abuse disorders. PMID- 1743659 TI - The quiet success of the national plan for the chronically mentally ill. AB - In 1978 the President's Commission on Mental Health called for a national plan for the care of persons with chronic mental illness. The plan was completed and released in 1980, but was never adopted as the policy of the incoming Reagan Administration. Despite changes in attitudes in the 1980s toward the federal government's role in human services and an atmosphere of fiscal restraint, many of the plan's specific recommendations for changes in Supplemental Security Income, Social Security Disability Insurance, Medicaid, and Medicare have been implemented. In this paper, the implementation of these recommendations is analyzed. The authors discuss some of the strategies used by mental health advocacy groups to make gains in the 1980s. Recommendations for the 1990s are discussed. PMID- 1743660 TI - Individual psychotherapy with schizophrenic outpatients in the public mental health system. AB - Forty-two therapists conducting individual psychotherapy with schizophrenic outpatients in a public mental health system responded to a questionnaire that focused on the types of interventions used and the issues and problems encountered in therapy. The therapists spent 59 percent of their time in supportive, problem-solving work and only 32 percent in traditional psychotherapeutic interventions, such as providing insight. The most common issues in therapy were relationship problems, family concerns, depression, losses, and the role of medications in the client's life. The most significant impediments to therapeutic work were the lack of community resources, the client's noncompliance with medications and lack of motivation, and dual diagnoses. Suggestions are offered for improving psychotherapy with schizophrenic outpatients in the public mental health system. PMID- 1743661 TI - Methodology for evaluating the Monroe-Livingston capitation system. AB - This paper presents the methodology for evaluating the Monroe-Livingston demonstration project's capitation payment system (CPS), based in Rochester, New York, for chronic mentally ill patients. To allow for both patient and provider choice within the experimental design, 1,587 CPS-eligible patients were randomly assigned at the start of the study to control or experimental conditions, with the intent of capturing in the experimental group a significant number of patients who would later be enrolled in the CPS. Protocols, which included measures of symptomatology, functioning, and resource utilization, were completed at baseline for 422 of the 605 patients contacted for inclusion in the study. The baseline control group included 143 patients; the experimental group included 279 patients, 153 of whom were eventually enrolled in the CPS. PMID- 1743662 TI - Can multiaxial diagnosis predict future use of psychiatric hospitalization? AB - Demographic and diagnostic intake data on about 10,000 patients at a public psychiatric facility were used to assess whether information recorded on various DSM-III axes could predict the frequency of patients' psychiatric hospitalizations over a follow-up period. Compared with patients who had been hospitalized only once or not at all, patients with three or more hospitalizations during the study period were more likely to be single and black and to come from lower social classes. They were more likely to have an axis I diagnosis of an alcohol-related disorder, a substance use disorder, or a psychotic disorder. When samples from the patient groups were matched on key demographic variables and primary axis I diagnosis, the multiaxial resources of DSM-III were not helpful in predicting future use of hospitalization. The results reinforce the importance of axis I diagnosis and demographic characteristics in assessing course and prognosis. PMID- 1743663 TI - Substance use disorders in patients with chronic fatigue. AB - A high prevalence of mood disorders has been found among persons with chronic fatigue. The comorbidity of mood disorders and substance use disorders has long been recognized. In this study, the prevalence of substance use disorders among 100 patients with chronic fatigue was examined. Twenty-eight patients met DSM-III R criteria for a lifetime diagnosis of substance abuse or dependence; ten of these patients had a current diagnosis. Forty-nine patients had no history of substance abuse or dependence but had other lifetime psychiatric diagnoses. Twenty-three patients had no history of substance abuse or psychiatric illness. No differences in demographic characteristics or in the features of chronic fatigue were found among the three groups. Patients with chronic fatigue who had a lifetime history of a substance use disorder reported more lifetime depressive symptoms and were more likely to have had suicidal ideation or attempts. PMID- 1743664 TI - Patterns of contact of patients' families with mental health professionals and attitudes toward professionals. AB - Previous studies have shown that many relatives of mentally ill persons are dissatisfied with their relationships with mental health professionals. In this study, 274 relatives or close friends of 168 recently discharged mental patients reported on 1,198 separate contacts with mental health professionals during the course of the patient's illness. Primary kin, such as parents and spouses, were most likely to be in contact with professionals. Different types of professionals were more likely to be in contact with relatives at different points in the patient's illness. Relatives' satisfaction varied significantly for the different types of professionals. Depending on the reason for the contact, 53 to 73 percent of the relatives reported being very satisfied or satisfied with the outcome. Respondents were most satisfied with their contacts with psychologists, followed by nurses, case managers, social workers, and psychiatrists. PMID- 1743665 TI - A program to help staff cope with psychological sequelae of assaults by patients. AB - Mental hospital staff who are assaulted by patients are at risk of developing symptoms associated with posttraumatic stress disorder. The Assaulted Staff Action Program (ASAP), a voluntary program, offers support to staff victims of patient assaults in a state mental hospital. ASAP team members debrief assault victims, assessing the victim's sense of control, social supports, and ability to make sense of the incident. A short-term support group is offered. During the program's first 90 days, the team responded to 67 assaults. Ten days after the assaults, many of the victims had not regained a sense of control, did not have a support network, and were unable to make sense of the incident. These factors put them at risk for PTSD symptoms. The costs of such a program are discussed. PMID- 1743666 TI - Use of inpatient psychiatric care at a VA medical center after implementation of a prospective payment system. AB - A retrospective audit of patients' utilization of inpatient psychiatric care at a Department of Veterans Affairs medical center before and after implementation of a prospective payment system compared patterns of utilization by chronic and nonchronic patients. It also examined changes over time in the size of the two groups, total number of bed days used, mean number of admissions, mean length of stay, and mean cumulative two-year length of stay. Four years after implementation of the prospective payment system, chronic patients constituted 3 percent of the patient population but used 15.2 percent of all bed days. Both chronic and nonchronic patients had a similar decrease in mean length of stay over the period, but chronic patients' mean number of admissions rose by more than 70 percent. The mean cumulative two-year length of stay of chronic patients remained stable over the period while that of the nonchronic patients decreased by 33.2 percent. PMID- 1743667 TI - Psychiatry in Zimbabwe. AB - Like many developing countries, Zimbabwe has a shortage of trained mental health professionals. The country is coping by developing an expanded role for nurses and other nonphysician mental health workers and by emphasizing use of medication in treating mental illnesses. The authors review traditional Zimbabwean beliefs about mental illness and healing and describe culturally specific patterns of illness presentation. To reverse the historic pattern in which psychiatric care was centralized in cities, Zimbabwe is establishing a countrywide system of primary health clinics, part of whose role is to screen and treat common mental disorders, educate communities about mental illness, and promote prevention of illness. PMID- 1743668 TI - Substance abuse among veterans with a diagnosis of schizophrenia. PMID- 1743669 TI - A comparison of referrals by police and other sources to a psychiatric emergency service. PMID- 1743670 TI - A mental health fellowship program in an HMO setting. PMID- 1743671 TI - Violence and ECA data. PMID- 1743672 TI - Limits on HMO benefits. PMID- 1743673 TI - Cost of monitoring clozapine. PMID- 1743674 TI - Combining approaches to care. PMID- 1743675 TI - The inpatient-outpatient gap. PMID- 1743676 TI - Research key element of plan to improve services for severely mentally ill persons. PMID- 1743677 TI - Data watch. Survey shows diverse demand for rehabilitation. PMID- 1743678 TI - This year's most quotable quotes: what health care leaders said about the issues. PMID- 1743679 TI - A decade of change: AHA's annual survey traces national trends, 1980-1990. PMID- 1743680 TI - Rising voices: how editorial writers looked at health care. AB - With attention turning to the nation's domestic problems and the 1992 presidential election coming up, the last quarter of 1991 saw a marked increase in the number of editorials and opinion pieces devoted to health care topics. Many newspapers and magazines targeted the broader--and thornier--issue of national health care reform, but narrower and no less critical issues also received play, including Medicaid underpayment, emergency department overcrowding and HIV testing for health care workers. PMID- 1743681 TI - Hospitals battle heart attacks with new chest pain centers. AB - Chest pain emergency centers are among the most popular new ambulatory care services being added in U.S. hospitals. In the past year, at least 80 hospitals have added such facilities, bringing the total to about 103 in 33 states, according to the Maryland cardiologist who pioneered the concept. Still, it remains to be seen whether these facilities will become a reliable long-term source of increased admissions. PMID- 1743682 TI - Weighing pros, cons of contract rehab services. PMID- 1743683 TI - Employee empowerment key to culture change. PMID- 1743684 TI - AHA and hospitals take shortcut to Data Bank. PMID- 1743685 TI - House bill slashes nurse education funding. PMID- 1743686 TI - New HCFA rule calls for electronic cost reports. PMID- 1743687 TI - Medicare change could benefit retirees under 65. PMID- 1743688 TI - Hospitals apply the lessons of PPS to RBRVS. PMID- 1743689 TI - Key discriminators in the manpower equation. PMID- 1743690 TI - Pathology trainee manpower: APC program directors' questionnaire, 1989 results. AB - The shortage of pathologists is being created by a combination of three factors: inadequate trainee recruitment, high trainee attrition, and accelerating practitioner attrition. The current report provides comprehensive data on the first two factors. The third factor is, by every estimate, likely to become worse over the decade beginning in 1988. Demographics show that greater numbers of pathologists will be reaching retirement age every year. The trainee attrition problem appears to be very serious, and we currently do not have data on why residents leave pathology training, when they leave, or where they go (ie, to what other specialties, etc). Future APC program directors' questionnaires must address these issues. Yet, we must also solve a serious problem in recruitment. Currently, about 35% to 38% of all first-year pathology residents decide to enter pathology only after entering residency programs in other specialties with the intent to remain in that specialty. Therefore, we need to recognize both the problem of inadequate recruitment and the problem of high attrition in order to address the serious manpower shortage facing pathology. When shortages occur in specialties, practitioners tend to cease performing the most time-intensive tasks (eg, autopsy). However, shortages of the magnitude predicted for pathology suggest that many more tasks traditionally performed by pathologists may very well be in jeopardy. In such a setting, other specialties (especially subspecialties) are likely to fill the void. This is likely to be catalyzed by the emergence of the new resource-based relative-value scale. Subspecialties in medicine and surgery will be looking for additional ways to retain income when they cannot expect as much for their services as before. This scenario is especially worrisome given the necessity for the practice of pathology to expand into the domain of molecular biology. Unless problems causing the shortage in pathology manpower are addressed, not only are our traditional practices threatened, we are also likely to have inadequate manpower to take advantage of those areas crucial for the future of pathology. PMID- 1743691 TI - Nuclear magnetic resonance in pathology: I. Principles and general aspects. AB - Nuclear magnetic resonance (NMR) has become established as a powerful diagnostic imaging technique in medicine. The power of NMR as a tool for characterizing molecular structure and for quantitative analysis of complex mixtures in the clinical laboratory or even in vivo is beginning to be exploited. In the clinical laboratory, NMR can analyze the complex mixtures of bodily fluids, intact cells, tissues, and their extracts. Phosphorus-31 or 1H NMR spectroscopy in vivo can provide a noninvasive probe of high-energy compounds, amino acids, and compounds of phospholipid metabolism. The basic principles of NMR spectroscopy are presented here, with emphasis on the various NMR parameters and the information they provide. A companion article presents a survey of applications in pathology. PMID- 1743692 TI - Flow cytometric DNA analysis of human solid tumors: a review of the interpretation of DNA histograms. AB - A survey of over 225 recent studies examining the relationship between the flow cytometric DNA analysis of solid tumors and clinical prognosis indicates that criteria used to classify DNA histograms are variable and often inconsistent with the recommendations proposed by the Convention on Nomenclature for DNA Cytometry. Numerous reports not only lack unambiguous descriptions of the histogram features used to differentiate diploid from aneuploid DNA distributions, but also inadequately describe the technical aspects of data acquisition, standardization, and inclusion or exclusion of subpopulations by gating. In many cases, the coefficient of variation of the diploid and aneuploid G0/1 peaks, which would allow an assessment of histogram quality, is not reported. Because of the differences in DNA histogram interpretation, extrapolation of the results among laboratories may be difficult and is probably not reliable. This review summarizes the criteria that have been used to classify the DNA histograms and illustrates the effects of these different classifiers on DNA ploidy analysis and clinical conclusions. PMID- 1743693 TI - The two forms of bronchiolitis obliterans in heart-lung transplant recipients. AB - Bronchiolitis obliterans has emerged as the major long-term complication of heart lung transplantation. We reviewed the histologic findings in lungs obtained from 11 patients who had received a combined heart-lung transplant at The Johns Hopkins Hospital. Ten lungs were obtained at autopsy, and one was obtained from a patient who was retransplanted because of severe bronchiolitis obliterans. Bronchiolitis obliterans was identified in seven of these 11 lungs. Three of the seven lungs with bronchiolitis obliterans were from patients who had received their transplants more than 6 months previously; the bronchiolitis obliterans in these patients was characterized by a relatively acellular concentric fibrosing process that was limited to the terminal bronchioles. The bronchiolitis obliterans in these three patients was felt to be secondary to chronic lung allograft rejection. Four of the seven patients with bronchiolitis obliterans had received their transplants less than 6 months previously; the bronchiolitis obliterans in these patients was focal and cellular. It extended into the distal alveolar spaces and, in several cases, was associated with aspirated material and foreign body-type giant cells. All four of these patients had concurrent infections, aspiration, or large airway obstruction, which were felt to be responsible for the development of bronchiolitis obliterans. Bronchiolitis obliterans in lung allograft recipients may have a variety of etiologies, and the etiology of this process in a particular case can often be deduced by the morphologic appearance of this lesion. PMID- 1743694 TI - Hepatic pathology in pediatric acquired immunodeficiency syndrome. AB - In a retrospective study we assessed the hepatic changes in children with the acquired immunodeficiency syndrome by reviewing 12 biopsy specimens and 48 autopsy specimens from 54 children. Hepatopathology differed in biopsy and autopsy material. In biopsy specimens, chronic active hepatitis with predominantly T8 lymphocytes by tissue immunochemistry was common (five of 12 specimens). Fatty degeneration and hepatocellular necrosis were either absent, mild, or patchy. On the other hand, at autopsy, chronic active hepatitis was not observed. The most prominent changes were extensive fatty degeneration, nonspecific portal mononuclear infiltration, portal fibrosis, and confluent (ischemic) necrosis. Opportunistic infections such as Mycobacterium avium intracellulare (MAI) were noted only at autopsy. In addition, three unusual morphologic characteristics were noted: nodular lymphoplasmacytic portal infiltrate, a pseudosarcomatous variant of Mycobacterium avium-intracellulare infection, and multinucleated giant cells (foreign both type and giant cell transformation of hepatocytes). PMID- 1743695 TI - Mineral-associated hepatic injury: a report of seven cases with X-ray microanalysis. AB - The patterns of hepatic injury associated with various minerals were studied in seven patients. The subjects included one patient who was a sandblaster (silica by inhalation), one patient who was a dental laboratory technician (silica and chromium-cobalt alloy by inhalation), one patient with inhalational talcum powder abuse, and four chronic intravenous (IV) drug abusers (talc by IV injection). In all cases, the liver was examined by light and polarizing microscopy, and by scanning electron microscopy with energy-dispersive x-ray microanalysis. In the two patients with silica exposure, silica-containing sclerohyaline nodules were diffusely present in portal tracts and lobules. Both chromium-cobalt alloy and silica were present in the dental technician. In contrast, in all cases of talc exposure, aggregates of talc-laden macrophages were present in portal and centrilobular areas. Three IV drug abusers and the talcum powder abuser had histologic evidence of chronic hepatitis, most probably of viral etiology. We conclude that mineral type plays an important role in the pathogenesis and fibrogenesis of hepatic lesions. Compared with silica, talc primarily elicits a macrophage response without granuloma formation or fibrosis. Hepatic silicosis is a rare complication in dental laboratory technicians, and chromium-cobalt alloy may contribute to hepatic injury and fibrosis in this setting. PMID- 1743696 TI - The pleomorphic xanthoastrocytoma and its differential diagnosis: a study of five cases. AB - Five brain tumors with the histopathologic features of pleomorphic xanthoastrocytomas (PXAs) are presented. Computed tomography scans showed a remarkable homology. Two cases had atypical localizations for a PXA, while one 46 year-old patient did not conform to the normal age distribution of this tumor. Nevertheless, in these cases, the histopathology was always characteristic for PXA, a remarkable pleomorphism, in addition to simultaneous expression of glial fibrillary acidic protein and histiocytic markers in the various tumor cells. In one of the presented tumors, however, clusters of neoplastic neuronal cells were also found. In this particular case, differential diagnostic criteria to distinguish between a PXA and a desmoplastic infantile ganglioglioma are lacking. PMID- 1743697 TI - Significance of the smooth muscle cell component in Peutz-Jeghers and juvenile polyps. AB - We have previously reported the presence of smooth muscle cells (SMCs) in the lamina propria of both tubular and villous adenomatous polyps. In the current study, we investigated the presence and distribution of SMCs with immunohistochemical techniques using anti-alpha smooth muscle actin and anti desmin antibodies on a series of hamartomatous polyps. In five Peutz-Jeghers polyps, large tree-like branches of SMCs were observed, while in 13 juvenile polyps, rare elongated SMCs were found in the lamina propria, partially surrounding cystically dilated glands. Apart from the quantitative differences, the SMC distribution was similar in the two types of hamartomatous polyps and not dissimilar from the pattern described in neoplastic polyps. These findings make the category "juvenile polyp" less clear and its differentiation from other histologic types of polyp less sharp. Thus, the presence or absence of SMCs cannot form the basis of the differential diagnosis between adenomatous and hamartomatous polyps. PMID- 1743698 TI - Rhabdomyolysis associated with cocaine abuse. AB - There have been recent reports of rhabdomyolysis associated with cocaine abuse. The pathologic findings from these cases have not been described. Pathologic abnormalities in two fatalities with cocaine-associated rhabdomyolysis, including one with hyperpyrexia, acute renal failure, and disseminated intravascular coagulation, are discussed in detail. Skeletal muscle in both cases showed necrosis without evidence of vasculitis, polarizable foreign crystals, or other specific lesions. The individual with renal failure showed acute tubular necrosis with granular myoglobin casts in tubules. The mechanism of cocaine-associated rhabdomyolysis is unclear, but potentially includes ischemia due to vasoconstriction, direct toxicity, hyperpyrexia, and increased muscle activity from agitation or seizure. Adulterants may also play a role. In unexplained cases of rhabdomyolysis, toxicologic evidence of cocaine should be sought. In those cases of rhabdomyolysis associated with acute renal failure, the presence of cocaine in blood may be prolonged because of impaired renal clearance. PMID- 1743699 TI - Flow cytometric study of nodular fasciitis, proliferative fasciitis, and proliferative myositis. AB - DNA ploidy was assessed retrospectively, using flow cytometry, in 13 nodular fasciitis (NF) lesions, three proliferative myositis (PM) lesions, one proliferative fasciitis lesion, and 12 other benign fibrous lesions (BFLs). All were diploid. In view of the large amounts of cellular debris, cell cycle analysis was possible in only seven NF lesions, three PM lesions, and six BFLs. The mean percentage of S phase did not differ markedly between the combination of NF and PM lesions (6.6%) and BFLs (7.1%); the mean percentage of G2 + M phase (5.4%) of the NF/PM lesion combination was twice as large as that of the BFLs (2.5%). No correlation was detected between the cell cycle analysis and the mitotic count, the predominant histologic type in NF lesions, or the predominant stroma in PM lesions. PMID- 1743700 TI - Angiocentric immunoproliferative lesions: a molecular analysis of eight cases. AB - Angiocentric immunoproliferative lesions (AILs) are believed to represent a unique type of extranodal malignant lymphoma on the basis of clinicopathologic and immunophenotypic evidence. However, molecular studies to assess clonality have been performed on a small number of cases. In this study we assessed the clonality of eight AILs using restriction fragment analysis, the Southern blot technique, and probes to assess the configuration of the T-cell receptor beta, gamma, and delta chain genes and the immunoglobulin heavy and K light chain genes. In addition, the presence of the Epstein-Barr (EB) viral genome was assessed by using both Southern blot analysis (seven cases) and polymerase chain reaction amplification (five cases). Our results demonstrate that gene rearrangements are rare in AILs. A clonal gene rearrangement was identified in only one case, a grade III AIL with a rearrangement of the T-cell receptor delta chain gene. In two additional AILs (both grade III), the EB viral genome was detected as a single band by Southern blot analysis with a probe derived from the terminal repeat region of the virus, suggesting that a single episomal configuration of the EB viral genome was present in each case, as would occur in a clonal population of infected cells. In the remaining cases there was no evidence of clonality, although EB sequences were detected in one of four cases using the polymerase chain reaction. The rarity or absence of gene rearrangements in AILs is difficult to explain if AILs are malignant, presumably monoclonal lymphomas. However, their frequent association with the EB virus may suggest an analogy between AILs and lymphoproliferative disorders that occur in immunosuppressed patients. These findings further emphasize the unique clinicopathologic aspects of AILs and may also be useful diagnostically in the differential diagnosis of lymphoproliferative disorders. PMID- 1743701 TI - Double muscularis mucosae in Barrett's esophagus. AB - To clarify the histology and morphogenesis of the double muscularis mucosae in Barrett's esophagus, eight specimens resected from patients with Barrett's esophagus were compared histopathologically with 352 specimens resected from patients without Barrett's esophagus. A double muscularis mucosae was observed in seven (87.5%) of the eight cases with Barrett's esophagus, but in none of the 352 cases without Barrett's esophagus. The mucosa in the segment of Barrett's esophagus consisted of columnar epithelium, a superficial lamina propria, a superficial muscularis mucosae, a deep lamina propria, and a deep muscularis mucosae. The distal end of the superficial muscularis mucosae was connected to the deep muscularis mucosae at the esophagogastric junction, and its proximal end was located in fibrous tissue below the squamocolumnar junction of the mucosal epithelium or the distal edge of the erosive lesion. The deep muscularis mucosae in the portion with Barrett's esophagus was continuous with the original muscularis mucosae of the proximal esophagus and muscularis mucosae of the stomach. Barrett's esophagus is considered to be not merely a metaplastic lesion within the epithelium, but a newly developed lesion containing columnar epithelium, lamina propria, and a superficial muscularis mucosae on the lamina propria of the esophageal mucosa. PMID- 1743702 TI - Paraganglioma of the urinary bladder: immunohistochemical, ultrastructural, and DNA flow cytometric studies. AB - Primary paraganglioma arises infrequently in the urinary bladder. We present the clinicopathologic, immunohistochemical, ultrastructural, and DNA flow cytometric findings in three cases (one man and two women). Ages at diagnosis were 19, 35, and 45 years. One female presented with paroxysmal headaches and hypertension that followed urination; the remaining two patients presented with hematuria. Immunohistochemical studies revealed positive reactivity for chromogranin (three patients), met-enkephalin (three), leu-enkephalin (three), vasoactive intestinal polypeptide (two), serotonin (one), and S-100 protein (one; sustentacular cells only). Neurosecretory granules were identified in all cases; in the patient with hypertension, the granules were small with eccentric cores similar to those of adrenal pheochromocytomas. A nondiploid DNA flow cytometric pattern was present in all three patients, an aneuploid pattern was present in two, and a tetraploid pattern was present in one. After diagnosis, one patient was alive without progression at 7 years, one died of an uncertain cause at 5 years, and one suffered multiple recurrences over a 24-year period before developing metastatic disease. While the presence of aneuploidy has been shown to be a predictor of malignant behavior in adrenal pheochromocytomas, our study illustrates that DNA ploidy cannot be used as a diagnostic criterion for malignancy in urinary bladder paraganglioma. PMID- 1743703 TI - Malignant ileal carcinoid with metastasis to adenocarcinoma of the ovary. AB - Metastasis of one tumor to another is an intriguing and rare phenomenon. Lung and breast malignancies are common donor tumors, while renal cell carcinoma and meningioma serve as frequent recipients. We report a case of malignant carcinoid of the ileum with metastasis to adenocarcinoma of the ovary. Histologic examination of the ovary showed a clear dimorphic pattern consisting of uniform polygonal cells arranged in an insular pattern and highly pleomorphic epithelioid cells forming small glands or solid nests. Immunocytochemical studies firmly established the distinct identity of the two tumors. PMID- 1743704 TI - Signet-ring chondrosarcoma: a new morphologic entity. AB - A 65-year-old, otherwise healthy white man presenting with an asymptomatic anterior chest wall mass diagnosed from a routine preoperative chest x-ray is reported. A fine needle aspirate of the mass was initially interpreted as a metastatic adenocarcinoma with prominent "signet-ring" features, but ultrastructural study of the cell block later suggested a chondrosarcoma. The resected surgical specimen confirmed the diagnosis of a grade 2 chondrosarcoma, with most of the tumor cells containing a large, clear, single vacuole shown to be lipid. The positive immunostaining for vimentin and S-100 as well as the ultrastructural appearance confirmed the diagnosis of a chondrosarcoma. Flow cytometric DNA analysis of the tumor on two separate occasions documented a very large aneuploid cell population (50% to 60%) which, when interpreted with the histologic appearance, suggested an aggressive tumor. This case illustrates the first published example of a "signet-ring" chondrosarcoma. PMID- 1743705 TI - Pigmented adrenal pheochromocytomas. PMID- 1743706 TI - The family and HIV. AB - The impact of HIV and AIDS on the family is described, with particular focus on the situation where the child is the first member of the family to be diagnosed. The results of the social stigma, the effect on relationships together with the global, economic and cultural aspects of the disease make it unique. These issues are discussed and an integrated approach to confidentiality, the provision of services for families and involvement of the community is described. PMID- 1743707 TI - Clinical, virological and immunological features of primary HIV-1 infection. PMID- 1743708 TI - Declining trends in some sexually transmitted diseases in Belgium between 1983 and 1989. AB - OBJECTIVE: To examine trends in some sexually transmitted diseases in Belgium and to discuss them in the light of the European background. DESIGN: Analysis of the time trends of C trachomatis and N gonorrhoeae infections diagnosed by a network of microbiological laboratories, and of male urethritis diagnosed by a network of general practitioners. SETTING: Belgium. SUBJECTS: Reports of C trachomatis and N gonorrhoeae infections by a network of microbiological laboratories, and of male urethritis by a network of general practitioners, to the Institute of Hygiene and Epidemiology. RESULTS: Whereas an increase in the number of C trachomatis infections, more pronounced among women, was observed up to 1986, a small decrease has been observed afterwards in males. The mean number of chlamydial infections per laboratory and per year was 4.2 in 1983, 15.7 in 1986 and 13.9 in 1989. A decrease in the number of N gonorrhoeae infections, more pronounced among men, has been observed. The mean number of cases of gonorrhoea per laboratory and per year was 10.9 in 1983 and only 2.2 in 1989. The same declining trend has been observed in another surveillance programme of male urethritis, based on a network of general practitioners. The number of cases of male urethritis per 100 patient encounters went down from 0.06 in 1982-3 to 0.04 in 1988-9. CONCLUSION: The declining trend in Western Europe in incidence of gonococcal infections and of urethritis in men is also occurring in Belgium, but genital chlamydial infections remain an important public health problem. PMID- 1743709 TI - The importance of ethnicity as a risk factor for STDs and sexual behaviour among heterosexuals. AB - OBJECTIVES: To study risk factors for sexually transmitted diseases (STDs) and sexual behaviour. Especially to assess whether there is a higher risk of being infected with STDs among ethnic minorities, and if so for what reasons. SETTING: STD-clinic of the Municipal Health Service of Amsterdam, the Netherlands. SUBJECTS: Cross-sectional study of heterosexuals (255 men and 343 women) with multiple sexual partners, who participated between October 1987 and January 1990. RESULTS: Besides STD-related complaints, ethnicity was an important independent predictor of one or more diagnosed genital STDs. STD-prevalence was higher among men born in Turkey (47%, OR = 3.4) and men born in Surinam (36%, OR = 2.1), compared with Dutch men (21%). While Turkish men had mainly riskful sexual behaviour with prostitutes, Surinam men had more often riskful sexual contact with private partners. Among women, STD prevalence was higher among West-European (38%, OR = 2.3) and Latin-American women (30%, OR = 1.6), compared with Dutch women (21%). Latin American women had more often riskful sexual contact with clients; sexual behaviour of West-European women was riskful with both clients and private partners. CONCLUSIONS: Prevention activities should be directed at specific sexual and ethnic groups, sources of information should be carefully selected, and some groups should be addressed differently with regard to language but to content as well. PMID- 1743710 TI - A survey of female prostitutes at risk of HIV infection and other sexually transmissible diseases. AB - OBJECTIVE: To determine risk factors for the transmission of human immunodeficiency virus (HIV), including injecting drug use (IDU), sexual behaviour and other sexually transmissible diseases (STDs), in female prostitutes who attended the Sydney Sexual Health (previously STD) Centre. DESIGN: We surveyed by questionnaire 231 (47%) of 491 female prostitutes who visited the Centre over a 19 month period from 1986 to 1988. All were tested for HIV antibody. MAIN OUTCOME: All the women were seronegative for HIV but a number of major risk factors for infection were identified. RESULTS: Seventeen of 26 (65%) current injecting drug users had shared needles in the previous 6 months. Nineteen per cent of those surveyed had bisexual non-paying partners and 21% had partners who injected drugs. Sixty nine per cent always used condoms for vaginal intercourse with paying clients, but they were rarely used with non-paying partners. Condom use was also rare for anal intercourse with clients and/or partners by those (18%) who practised it. Seventeen per cent used condoms alone for contraception and 48% relied on oral contraceptives. We found a reduction in gonorrhoea, herpes and trichomoniasis when compared with a 1985 study conducted at the same Centre. However, there was an increase in reported abnormal cervical cytology. CONCLUSION: In spite of behaviour change by some, there are still many women working as prostitutes in Sydney who remain seriously at risk of HIV infection. We recommend more widespread use of barrier methods of contraception, intensified efforts to prevent the sharing of intravenous needles, closer monitoring of the health of prostitutes, and scientific study of their paying and non-paying sexual partners. PMID- 1743711 TI - Characterisation of PPNG and non-PPNG Neisseria gonorrhoeae isolates from Singapore. AB - OBJECTIVE: To characterise Neisseria gonorrhoeae isolates from Singapore. DESIGN: Characterisation of Neisseria gonorrhoeae isolates by auxotyping, serological analysis and plasmid profile analysis. SPECIMENS: Sixty randomly collected isolates from 41 symptomatic, untreated males and 19 female prostitutes were studied. RESULTS: Auxotyping of 25 PPNG and 35 non-PPNG strains showed that the Pro-auxotype was prevalent among both PPNG (56%) and non-PPNG (42.5%) strains. Prototrophic strains comprised 28% of PPNG and 32.5% of non-PPNG strains respectively. Serovar analysis showed that with the exception of seven serogroup WI strains, the majority belonged to serogroup WII/III. Serovar Aedih was predominant among both serogroup WI PPNG (80%) and non-PPNG (100%) strains. Serogroup WII/III PPNG strains were represented by nine serovars with the predominant serovars being Bacjk (28%) and Bcgjk (16%). Eleven serovars were identified in the WII/III non-PPNG strains and the major serovars were Bajk (20%), Bacjk (17%), Back (11.4%) and Beghjk (11.4%). Analysis of the 25 PPNG strains showed that 16 of them carried the 4.4 MDa (Asian type) resistance plasmid and nine strains harboured the 4.4 MDa plasmid in conjunction with the 24.5 MDa transfer plasmid. The cryptic plasmid of 2.6 MDa was present in 27 of the 35 non-PPNG strains. Five of the non-PPNG strains harbouring the cryptic plasmid also contained the 24.5 MDa transfer plasmid. The plasmid combination of 2.6 + 7.8 + 24.5 MDa was detected in three non-PPNG strains. CONCLUSION: The combination of epidemiological methods used in this study indicated the heterogeneity of N gonorrhoeae strains in Singapore. A total of 16 different combinations of auxotype, plasmid profile and serovar were seen in the 25 PPNG strains compared with 24 such combinations in the 35 non-PPNG strains. Such sensitive differentiation would otherwise not be possible using either auxotype serovar (A/S) or auxotype-plasmid analysis. PMID- 1743712 TI - A comparison of interferon alfa-2a and podophyllin in the treatment of primary condylomata acuminata. The Condylomata International Collaborative Study Group. AB - OBJECTIVES: to compare the response to treatment and recurrence rate of condylomata accuminata using subcutaneous injection of interferon alfa 2a 1.5 million units three times weekly for four weeks, or podophyllin resin 25% applied to lesions twice weekly for up to six weeks. DESIGN: Randomised open study. SETTING: Multicentre European study in genitourinary medicine, dermatovenereology, and gynaecology departments. PATIENTS: 87 males and 67 females with condylomata acuminata for less than six months and no history of previous treatment. MAIN OUTCOME MEASURES: Complete clearance of lesions and evidence of recurrence at three months and nine months after treatment commenced. RESULTS: A complete response was achieved at three months in 15 of 64 (23%) in the interferon treated group, and 31 of 69 (45%) in the podophyllin treated group (p = 0.003). At nine months 10 of 13 patients in the interferon group and 22 of 30 patients in the podophyllin group remained completely clear of lesions. PMID- 1743713 TI - HLA antigens in donovanosis (granuloma inguinale). AB - OBJECTIVE: To compare the frequencies of HLA antigens in patients with donovanosis and in controls. DESIGN: HLA Class I, Class II and DQ antigens were detected in patients with genital ulceration caused by donovanosis and in a control group. SETTING: City Health STD Clinic, King Edward VIII Hospital, Durban, South Africa. Participants--Sixty (47 men, 13 women) patients with donovanosis. RESULTS: HLA B57 was detected in nine of 60 (15%) with donovanosis and 75 of 1478 (5.1%) controls (RR = 3.3 chi 2 = 11.0, p = 0.001, p corrected = 0.026). CONCLUSIONS: A possible link between donovanosis and HLA B57 could be explained by coexisting alleles or immune response genes in linkage disequilibrium altering disease susceptibility. PMID- 1743714 TI - Ultrastructural aspects of infection with Treponema pallidum subspecies pertenue (Pariaman strain). AB - OBJECTIVE: To study ultrastructural aspects of infection with Treponema pertenue (Pariaman strain), originating from West Sumatra, Indonesia. MATERIALS AND METHODS: Biopsy material originating from skin lesions in ten young children suffering from early infectious yaws in Indonesia, and rabbit testicular tissue inoculated with T pertenue. Human skin as well as rabbit testicular tissue was examined by means of conventional electron microscopy. RESULTS: In human skin, treponemes were found in interepidermal spaces in 5 out of 10 specimens. In two of five positive specimens, treponemes were also seen in the dermis. In one out of five specimens from rabbit testicular tissue a profusion of treponemes was found lying in the interstitial myxomatous tissue. Microorganisms showed no adhesion to fibroblasts. CONCLUSION: This ultrastructural study of T pertenue demonstrated the scarcity and focal distribution of treponemes in tissue and did not reveal any morphological differences from the Gauthier strain of T pertenue. No differences from the ultrastructure of T pallidum were observed either. PMID- 1743715 TI - An analysis of false positive reactions occurring with the Captia Syph G EIA. AB - AIM: The Captia Syph G enzyme immuno assay (EAI) offers the potential for the rapid automated detection of syphilis antibodies. This study was designed to assess the role of other sexually transmitted diseases (STDs) in producing false positive reactions in the Captia Syph G EIA. The role of rheumatoid factor (RF) as a potential source of false positives was also analysed. METHODS: Patients who attended a genitourinary medicine (GUM) department and gave a false positive reaction with the EIA between 1988 and 1990 were compared with women undergoing antenatal testing and with the control clinic population (EIA negative) over the same time period. The incidence of sexually transmitted disease (STD) in the clinic population and the false positive reactors was measured in relation to gonorrhoea, chlamydia, genital warts, candidiasis, "other conditions not requiring treatment" and "other conditions requiring treatment." Male: female sex ratios were also compared. Ninety two RF positive sera were analysed with the EIA. RESULTS: The rate of false positive reactions did not differ with respect to the diagnosis within the GUM clinic population. The antenatal group of women, however, had a lower incidence of false positive reactions than the GUM clinic group. No RF positive sera were positive on Captia Syph G EIA testing. CONCLUSIONS: There is no cross reaction between Captia Syph G EIA and any specific STD or with RF positive sera. The lower incidence of false positive reactions in antenatal women is unexplained but may be related to physiological changes associated with pregnancy. PMID- 1743716 TI - Multiple prostatic abscesses presenting with urethral discharge. AB - Prostatic abscess has become less common, is now usually related to urinary tract infection, and is a rare cause of urethral discharge. The case is described of a man with prostatic abscesses caused by Staphylococcus aureus possibly related to recent skin abrasions. Transrectal ultrasound was used to make the diagnosis and to facilitate repeated drainage with a successful outcome. PMID- 1743717 TI - HIV encephalopathy presenting as hypomania. PMID- 1743718 TI - The Gist-Brocades travelling fellowship, 1990. PMID- 1743719 TI - Should training in colposcopy be obligatory in higher specialist training in genitourinary medicine? PMID- 1743720 TI - HIV infection in Tirupati, India. PMID- 1743721 TI - Endemic syphilis in Bulgaria. PMID- 1743722 TI - Incidence of Neisseria gonorrhoeae and Chlamydia trachomatis infections in Strasbourg over 8 years. PMID- 1743723 TI - Female paraurethral ducts and glands as the sites of agents of sexually transmitted diseases. PMID- 1743724 TI - Treatment of genital herpes with chlorous acid releasing gel. PMID- 1743725 TI - Nd:Yag laser treatment of extensive recalcitrant anal condyloma acuminata. PMID- 1743726 TI - Complications of treatment for cryptosporidial diarrhoea. PMID- 1743727 TI - Cervical infection with Chlamydia trachomatis. PMID- 1743728 TI - Syphilis and the elderly. PMID- 1743729 TI - Frequency analysis of the electrocardiogram with maximum entropy method for identification of patients with sustained ventricular tachycardia. AB - Late potentials in the terminal phase of the QRS-complex during sinus rhythm have been proposed to identify a subgroup of patients with myocardial infarction at risk of ventricular tachycardia (VT). Frequency analysis of the ECG with Fourier transform (FFT) has been applied for detection of these microvolt level signals, but is limited by poor frequency resolution of short data segments and spectral leakage. We therefore developed frequency analysis using the maximum entropy method (MEM) based on an autoregressive (AR) model. Orthogonal electrocardiograms were recorded from the body surface of patients with and without VT, and healthy persons after low noise, high-gain amplification. Multiple 40 ms segments (time intervals 2 ms, AR-parameters tapered) were analyzed (spectrotemporal mapping): low-frequency components were eliminated by building difference spectra with optimal high order and fixed low order. The MEM-spectra revealed high frequency components (40-200 Hz) in the terminal phase of the QRS-complex and in the ST section in 26/38 patients with VT, but only in 2/20 without VT and in 1/20 healthy persons (p less than 0.05). Unlike FFT, MEM allowed localization of late potentials by the analysis of short data segments. Thus, MEM offers promise for noninvasive identification of patients with sustained VT after myocardial infarction and detailed analysis of late potentials. PMID- 1743730 TI - Optimal a posteriori time domain filter for average evoked potentials. AB - Evoked potentials measured with scalp electrodes are often described as a deterministic process corrupted by unrelated noise. The common procedure to determine the signal is to average N repetitive measurements. By obtaining additional information from the N measurements, signal detection can be improved. An algorithm that estimates the signal autocorrelation from N given measurements is proposed. The estimator is consistent and unbiased, and its variance tends to 0 as o(N). Two filters that are applied to the average response are introduced. Both depend on the estimation of the signal and the noise autocorrelations. One filter is based on the assumption that the average response is a stationary process. The second filter coefficients are obtained by minimizing the mean squared error (MSE) of an optimal filter of a nonstationary process applied on a single sweep. When a small number of sweeps are averaged, the stationary assumption is adequate, and the MSE of the stationary optimal filter is two to five times less than the MSE of the average response. When a large number of measurements are considered, the error in estimating the autocorrelations decreases. In this case, applying the optimal filter for a nonstationary process leads to a significant improvement in the signal estimation. PMID- 1743731 TI - Nonlinear system identification by m-pulse sequences: application to brainstem auditory evoked responses. AB - The purpose of this paper is to introduce a method for characterizing the nonlinear behavior of the auditory system. The method uses an m-pulse sequence as the stimulus and employs a general nonlinear framework for the auditory system. Like Sutter's binary m-sequence approach, the m-pulse sequence approach is computationally efficient since calculation of the first-order input-output cross correlation function is all that is necessary for obtaining the nonlinear characteristics of the system. The nonlinear system characteristics are reflected in pulse kernels in contrast to binary kernels associated with the binary m sequence approach. By assuming the system under study is a third-order nonlinear system, binary and pulse kernels are shown to be related to Volterra kernels. The results suggest that the m-pulse sequence can be used to study the system nonlinear effects of varying the stimulus repetition rate more effectively than conventional methods. Preliminary physiological data obtained by applying m-pulse sequences to the brainstem auditory evoked response (BAER) clearly illustrates the feasibility of obtaining replicable evoked responses using this method. PMID- 1743732 TI - Information contained in sensory nerve recordings made with intrafascicular electrodes. AB - Multiunit recordings were made in anesthetized cats with chronically implanted intrafascicular electrodes over a period of six months. Neural signals recorded with these electrodes consisted of activity in sensory fibers innervating a variety of cutaneous mechanoreceptors. Mechanical stimuli were used to selectively activate individual nerve fibers, and the receptive field and receptor type were identified for each unit. Over a period of six months, there was a net shift in the recorded population, but the electrodes continued to provide a representative sample of the activity in the fascicle as a whole. The total number of units from which activity could be recorded remained roughly constant with time, and individual units persisted in the recordings for up to six months. These results indicate that intrafascicular electrodes could be used to sample information carried by individual somatosensory fibers on a long term basis. PMID- 1743733 TI - Influence of tissue inhomogeneities on noninvasive muscle fiber conduction velocity measurements--investigated by physical and numerical modeling. AB - The determination of conduction velocity in the muscle fibers of single motor units from noninvasive recordings of single motor unit action potentials can be improved by the method of spatially filtering multielectrode EMG. The use of this conduction velocity as a diagnostic tool requires a high reliability of the detected values. However, experiments did reveal that the measured conduction velocity values showed remarkably high fluctuations depending on the recording site along the muscle fibers which could not be attributed to the influence of the endplate and tendon region. The present work examines the hypothesis that the observed fluctuations in propagation velocity were caused by electrically inhomogeneous tissue, regions of different electrical conductivity which are located between the excited muscle fibers and the recording electrodes and which cause a deformation of the extracellular electric current field. The investigation was performed by means of a physical model as well as by finite element model calculations. In both models single, simple shaped (cylindrical) inhomogeneity regions with a conductivity of 0.1 to 10 times that of the surrounding medium and diameters ranging between 1.6 and 2.7 mm were placed between excitation sources and recording site. The results indicate that the observed conduction velocity fluctuations of up to some 10% can be well attributed to inhomogeneity effects of the tissue conductivity. Based on these results, one may look for signal processing methods to cut down such fluctuations in conduction velocity measurements. PMID- 1743734 TI - Computer-aided design of two-dimensional electric-type hyperthermia applicators using the finite-difference time-domain method. AB - A hyperthermia applicator design tool consisting of a finite-difference time domain (FDTD) technique in combination with a graphical display of electric fields and normalized linear temperature rise is described. This technique calculates, rather than assumes, antenna current distributions; it includes mutual interactions between the body and the applicator, and it calculates driving-point impedance and power delivered to the applicator. Results show that the fundamental limitation of 2-D electric-type applicators is overheating of the fat by normal components of the electric field, which exist because of near fields and capacitive coupling with the muscle. Two factors which contribute to the capacitance are the muscle conductivity and the small antenna size in air. Two examples of applicators designed to avoid fat overheating are described: a 27 MHz segmented dipole for heating large tumors to 7 cm depth, and a 100-MHz dipole for small tumors to 5 cm depth. The first uses a water bolus, and the second uses a water bolus with low-permittivity strips to reduce normal fields at the antenna ends. The results of this study describe fundamental limitations of electric field applicators, and illustrate the use of a powerful applicator design tool that allows rapid evaluation of a wide range of ideas for applicators which would require months and years to test experimentally. PMID- 1743735 TI - Eccentric spheres models of the head. AB - Equations are derived for electric potentials (electroencephalograms) and magnetic fields (magnetoencephalograms) produced by dipolar sources in three eccentric spheres models of the head. In these models, I) the thickness of the layer representing the skull varies around the model, II) the thickness of the scalp layer varies, and III) the electrical conductivity of an eccentric spherical "bubble" in the brain region varies. Using these equations, it was found that variations in these features of the models have at most only small effects on the general spatial patterns of the electric potentials and the radial component of the magnetic fields. However, some significant effects on the amplitudes were found. The effects of the variations in the skull and scalp layer thicknesses on the field amplitudes were found to be significantly smaller than on the potential amplitudes. The effects on the field amplitudes of the variations in the bubble conductivity were found to be only somewhat smaller than on the potential amplitudes. It was also found that the effects of variations in these features of the models on source localization accuracy were significantly smaller for inverse solutions using fields than for solutions using potentials. PMID- 1743736 TI - A model for the cortico-cortical neural interaction in multisensory-evoked potentials. AB - This paper addresses the methodological problem of enhancing selective responses from the central nervous system when two (or more) different sensorial stimuli are simultaneously presented to the subject. In particular, contemporaneous visual and somato-sensory stimulation is considered and a model of signal and noise interaction is developed for the processing of the evoked responses. An ARXX parametric model (AutoRegressive with two eXogenous inputs) is introduced and a least squares algorithm is used to determine the selective response of the two neural systems from the overall evoked response. Such an analysis may be also carried out on a sweep-by-sweep basis. Applications of this method are the following ones: i) modeling of multisensory potentials; ii) description of facilitation or defacilitation phenomena in multitasking experiments; iii) analysis of cortico-cortical neural interactions. PMID- 1743737 TI - A control method for a nonlinear multivariable system: application to interstitial laser hyperthermia. AB - An original adaptive control method is presented for controlling a nonlinear multivariable system. The method, which could be described as a modified quasi linear approach, involves dividing the source excitation into a series of pulsing rounds and is implemented as a control algorithm on a computer. The theory underlying the method is developed with reference to an application involving temperature control in interstitial laser hyperthermia. In this application, the method is both successful and necessary to achieve optimally uniform elevated temperatures in a ground beef phantom. Apart from variable and parameter definitions, the method is otherwise general and might be useful for controlling a nonlinear system in which no prior exact characterization of the system is possible. Simulations were conducted to assess the effectiveness of the method in systems for which the unit excitation response changes by factors ranging from zero to three over the total period of excitation. In each case the method has proven stable. PMID- 1743738 TI - Goniometric motion controller for the superconducting coil in a magnetic stereotaxis system. AB - For the purpose of positioning the 80 kg, 2 T superconducting coil/cryostat used in the developmental version of a magnetic stereotaxis system, a four degree-of freedom goniometer has been designed, built, and tested. Computer-controlled, stepping motor actuators enable movement of the coil via either joystick, keyboard, or translator-module keypad commands. An integral arrangement of counterweights and counterbalances minimizes the overall weight and size of the goniometer, while maintaining static and dynamic stability during operation. As much of the structure as possible has been made of nonmagnetic materials (mostly aluminum) to minimize distortion of the superconducting coil's field. In this paper, we present the design principles for the goniometer, describe the essential features of its construction, and discuss its performance characteristics and limitations. We also discuss a strategy for performing precision magnetic stereotaxis procedures with an arrangement of static superconducting coils. PMID- 1743739 TI - A quantitative analysis of pendular motion of the lower leg in spastic human subjects. AB - The purpose of this study was to examine gravity-induced oscillations of the lower leg in normal and spastic subjects, with a view towards evaluating a clinical test of spasticity called the "pendulum" test. Motivations for studying the pendulum test were to determine if realistic aspects of spasticity and neuromuscular control could be incorporated into a description of the motion, and to better understand the underlying neurophysiological disturbances in spasticity. For passive limb motion (in which no reflex excitation occurred), a second-order linear model did not provide an adequate description of the motion for either spastic or normal legs. Instead, system equations including nonlinear mechanical properties simulating asymmetries in the swing and amplitude dependent variations in stiffness and damping provided a more accurate description. For spastic limb motion (in which reflex excitation did occur), accurate simulation required components accounting for abnormal reflex activation, coinciding with the time course of EMG activation. These included increased stiffness and damping with their gains related to reflex EMG magnitude, and changes in the rest length of the stiffness. Comparison of numerical solutions of the equations with experimental data showed our nonlinear model simulated the motion accurately, with the variance accounted for usually exceeding 90%. PMID- 1743740 TI - A low-cost fiber-optic strain gage system for biological applications. AB - A new low-cost strain measurement system has been developed for the mechanical testing of biological soft tissues. The technique creates four spots of light on a tissue sample surface by piercing the tissue sample with two pairs of small light-conducting optical fibers (one pair for each axis of a biaxial stretch), terminated by high intensity infrared emitters. A large-area photodiode, located below the tissue sample, detects the light emitted from the two pairs of light spots. Analog and digital circuitry analyze the current signal from the photodiode to determine the position of a light-spot in real time. Each infrared emitter is sequentially cycled "on" at a rate of 3 kHz and the resulting photodiode current signal, after being converted to a voltage signal, is held by an integrated circuit sample and hold amplifier. Analog differencing of pairs of light-spot voltage signals provides a final output proportional to the separation between coaxial light-spots. PMID- 1743741 TI - A water-cooled EM applicator radiating in a phantom equivalent tissue- experiments and numerical analysis. AB - A prototype of a water-cooled electromagnetic applicator for intracavitary hyperthermia has been tested. The temperature distributions produced in a polyacrylamide dissipative medium have been shown using liquid crystals. A complete electromagnetic and heat transfer model can predict the experimental temperatures. PMID- 1743742 TI - Laser Doppler velocimetry stabilized in one dimension. PMID- 1743743 TI - A clinico-radiological study of secondary mycoses in pulmonary tuberculosis. AB - Clinical and radiological differences were compared in Fungus positive (74) and negative (66) cases of pulmonary tuberculosis. Cough, expectoration, dyspnoea, and fever were marked in former group than that of latter. Anaemia, leucocytosis, raised ESR, abnormal radiological shadows and mycetoma in healed cavity were also noted in significant number in fungus positive cases. PMID- 1743744 TI - Epidermoid cyst of the spleen--with unusual findings. A case report. AB - Epidermoid cyst in a six and half year old male child is reported. The cyst was quite huge thereby reducing the splenic tissue. Histologically the epithelial lining showed dysplastic changes and unusual calcification of the collagenous connective tissue. PMID- 1743745 TI - Tritium metabolism in man. AB - Tritium metabolism in human beings was studied in volunteers who had exposure to tritiated water accidentally, by measuring the organically bound tritium with liquid scintillation counter, in sperms and plasma proteins. 2% of the initial urinary tritium specific activity was incorporated as bound tritium in sperms. In plasma proteins, on the 20th day of exposure, tritium bound in globulin was 3 times higher than that of albumin, tritium bound in globulin was 3 times higher than that of albumin. PMID- 1743746 TI - Comparison of latex agglutination test with the standard ASO test for antistreptolysin O antibodies. PMID- 1743747 TI - Startle epilepsy--a case report. PMID- 1743748 TI - Height-weight relationship in young healthy Indian girls. AB - The relationship between height and weight in young healthy Indian girls (8--18 years) was developed. It is concluded that the relationship of the form:log w = 0.98 h + 0.14 holds good to the data on height h (in metres) and weight w (in kilograms) for this group of subjects, the logarithm is taken to the base 10. The results of the present study show that Ehrenberg's equation of the form : log w = 0.8 h + 0.4 may not be extended upto the age of 18 years in young healthy Indian girls. PMID- 1743749 TI - Intestinal parasitism in Himachal Pradesh. AB - A total of 1629 cases were included in the study for the presence of intestinal parasites during 12 mobile camps in different areas of Himachal Pradesh. 47.08% were positive for parasites. The prevalence rate of helminthic parasites was 32.41% and that of protozoal parasites was 20.81%. The parasitic prevalence has been discussed in the light of peculiar geographical situation of the area. PMID- 1743750 TI - A possible role of caesium radiations in the control of propagation of hookworm. AB - Faeces charcoal mixtures containing eggs of sheep hookworm, Haemonchus contortus were exposed to caesium radiations (23 r to 1656 r) from 1st to 7th day of incubation. Each plate was exposed only once. A dose related inhibition of transformation of eggs to infective larvae was observed. The maximum effect was observed on 2nd day of incubation. The radiation has maximum effect on the 1st stage larvae followed by 2nd stage. The 3rd stage or ineffective larvae are relatively resistant to the effect of radiation. PMID- 1743751 TI - A pilot study of parenteral lincomycin therapy in soft tissue infections. AB - From our study it is clear that lincomycin, given 300 mg intra muscularly daily in a single dose, is effective in a wide range of soft tissue infections especially those involving the head and neck region. An overall success rate of 88.8 per cent was observed in the 150 patients selected for the study. It is significant that in none of the subjects was any untoward reaction observed or reported. Hitherto all the previous systematic surveys on lincomycin appear to have been carried out on bone infections where, undoubtedly, lincomycin is highly effective. This pilot study furnishes an encouraging report on the successful treatment of soft tissue infections with parenteral lincomycin. PMID- 1743752 TI - High vaginal swab(HVS), routine microscopy and culture sensitivity in diabetic and non diabetic, a comparative retrospective study of five years. AB - Diabetic women are significantly more prone to develop vaginitis (both bacterial and fungal) than non diabetic. Among the positive cases predominant bacterial isolate being E. Coli. All fungus positive culture yielded the growth of candida species. Direct wet film preparation of the fungus positive cases revealed only 30% were positive for fungus, thus if candida vaginitis is suspected, the diagnosis cannot be ruled out on the basis of negative direct preparation. More over, diabetics should be advised maintain proper glycaemic control and personal hygiene to get rid of this distressing problem. PMID- 1743753 TI - Is pulse pressure a stimulus for altered vascular structure in chronic hypertension? PMID- 1743754 TI - Nerve growth factor synthesis in vascular smooth muscle. AB - Details of the interdependent, trophic relation between smooth muscle and its neural innervation are not well known despite suggestions that neural influences may contribute significantly to hypertensive and other cardiovascular disease. Vascular smooth muscle is a major target of innervation by neurons of the sympathetic nervous system. Sympathetic neurons depend on a constant supply of the potent neurotrophic peptide nerve growth factor. Nerve growth factor regulates an impressive list of neuronal and perhaps muscle properties, yet its source in vessels and the determinants of its synthesis are not known. We have taken advantage of the cytoarchitecture of the aorta to demonstrate that vascular smooth muscle cells synthesize nerve growth factor. The survival of cultured sympathetic neurons is supported in a nerve growth factor-dependent manner by co culture with pure rat aortic vascular smooth muscle cells. Furthermore, pure smooth muscle cell cultures contain nerve growth factor-specific messenger RNA. Levels of messenger nucleic acid coding for nerve growth factor in smooth muscle are regulated by contractile agonists (angiotensin II, arginine vasopressin) and the adrenergic agonist phenylephrine. This suggests a link between muscle activity and growth factor production. Secretion of nerve growth factor protein by vascular smooth muscle was measured using a sensitive two-site immunoassay. Secretion is highest during muscle growth. Secretion is elevated by angiotensin II and arginine vasopressin but slightly inhibited by phenylephrine. These results suggest that cultured vascular smooth muscle can serve as a useful model in which to study the cellular regulation of trophic factor synthesis in health and disease. PMID- 1743755 TI - Regulation of insulin-like growth factor I messenger RNA levels in vascular smooth muscle cells. AB - We have previously demonstrated specific insulin-like growth factor I (IGF I) messenger RNA (mRNA) transcripts in cultured rat aortic smooth muscle cells (RASM). To define the role of IGF I in the autocrine growth program of vascular smooth muscle cells, we quantitated IGF I mRNA levels in proliferating and quiescent (serum-deprived for 48 hours) RASM. IGF I mRNA levels were markedly decreased in quiescent cells, and this effect was reversible on reexposure to serum. Since platelet-derived growth factor (PDGF) acts synergistically with IGF I to stimulate vascular smooth muscle cell growth, we exposed quiescent RASM to PDGF AB or BB and quantitated IGF I transcript levels. Both PDGF dimers caused a marked, rapid increase in IGF I message levels. To determine whether induction of IGF I mRNA levels correlated with secretion of IGF I, we measured immunoreactive IGF I in RASM conditioned medium after separation of IGF I binding proteins by gel filtration chromatography. PDGF caused a significant increase in IGF I release at 24 hours. These findings indicate that IGF I mRNA levels in vitro are regulated by serum and by growth factors such as PDGF. Serum deprivation reversibly decreases IGF I transcript levels, and exposure of quiescent cells to PDGF increases IGF I mRNA levels and IGF I release. Regulation of IGF I expression by competence growth factors such as PDGF may play an important role in the control of vascular smooth muscle cell growth. PMID- 1743756 TI - Lipid bilayer in genetic hypertension. AB - Membrane microviscosity, phospholipid composition, and turnover were measured in cultured vascular smooth muscle cells isolated from mesenteric arteries of stroke prone spontaneously hypertensive and age-matched, normotensive Wistar-Kyoto rats. Membrane microviscosity, measured with fluorescence polarization, revealed greater microviscosity (lower fluidity) of the membranes isolated from smooth muscle cells from hypertensive as compared with those isolated from normotensive rats (p less than 0.01). Preincubation of membranes from hypertensive rats with 5 mM calcium reduced membrane microviscosity in "core" and in "surface" regions of the bilayer toward values observed in Wistar-Kyoto rats. Phospholipid composition did not differ between intact aortas and cultured mesenteric cells or between those tissues obtained from normotensive and from hypertensive rats. The total lipid-associated radioactivity was significantly lower in cells from stroke-prone spontaneously hypertensive rats than in those from Wistar-Kyoto controls (p less than 0.01). Phosphatidylcholine incorporated 70% and phosphatidylinositol 16% of total lipid-associated radioactivity, with no difference between cells from hypertensive and normotensive animals. Turnover of phosphatidylethanolamine was greater in cells from Wistar-Kyoto rats (p = 0.02), whereas turnover of phosphatidylserine was greater in cells from stroke-prone spontaneously hypertensive rats (p = 0.04). The greater microviscosity of the lipid bilayer in hypertension is a generalized defect of the matrix in which the transport proteins function. We hypothesize that this defect is responsible for the multiple abnormalities of membrane transport systems that have been described in genetic hypertension. PMID- 1743757 TI - Rise and fall of agonist-evoked platelet Ca2+ in hypertensive rats. AB - We previously reported an enhanced peak response of intracellular free Ca2+ to thrombin in platelets of spontaneously hypertensive rats in comparison with normotensive Wistar-Kyoto rats. In the present study, we compared the platelet intracellular Ca2+ response to the receptor-linked agonist thrombin with the response to the Ca2+ ionophore ionomycin. Basal intracellular Ca2+ was higher in hypertensive platelets as was leakage of fura-2. We confirmed the previous finding that the thrombin-induced intracellular Ca2+ peak is greater in platelets of hypertensive rats and noted that the rate of recovery from peak intracellular Ca2+ is significantly greater in this model. In contrast, the peak platelet intracellular Ca2+ response to ionomycin (50 nM and 5 microM) was not different between the two strains, and the rate of recovery from the peak response was only slightly depressed in hypertensive rats after the low dose of ionomycin. Internal Ca2+ discharge capacity, assessed by the intracellular Ca2+ response to a maximal dose of ionomycin in Ca(2+)-free medium, was not different between platelets of the two strains. Thus, activated platelet intracellular Ca2+ is not altered in the hypertensive rat when the nonphysiological ionophore ionomycin is used as agonist. However, a heightened intracellular Ca2+ response is observed when the receptor-mediated agonist thrombin is used. These results are consistent with the hypothesis that differences in receptor-linked second messenger pathways underlie the altered intracellular Ca2+ response in platelets of genetically hypertensive rats and may contribute to differences both in the mobilization of Ca2+ and in its fall. PMID- 1743758 TI - Effects of angiotensin subtype 1 and subtype 2 receptor antagonists in normotensive versus hypertensive rats. AB - The purpose of this study was to examine in vivo the importance of angiotensin subtype 1 (AT1) versus subtype 2 (AT2) receptors in spontaneously hypertensive (hypertensive) versus normotensive Wistar-Kyoto (control) rats. Intravenous infusions of DuP 753, a selective AT1 receptor antagonist, abolished the pressor responses to intravenous infusions of angiotensin II in both strains, and the potency of DuP 753 in this regard was similar in the two strains. DuP 753 also abolished angiotensin II-induced aldosterone release in both strains; however, with respect to inhibiting angiotensin II-induced aldosterone release, DuP 753 was more potent in hypertensive compared with control rats. In hypertensive but not control rats, DuP 753 inhibited angiotensin II-induced aldosterone release at doses lower than required to inhibit angiotensin II-induced pressor responses. Intramesenteric infusions of DuP 753 abolished mesenteric vascular responses to intramesenteric infusions of angiotensin II with a similar potency in both strains. In control but not hypertensive rats, angiotensin II consistently potentiated noradrenergic neurotransmission in the mesenteric vascular bed, and this effect of angiotensin II was abolished by DuP 753. High doses of PD123177, a selective AT2 antagonist, did not influence any of the aforementioned effects of angiotensin II in either strain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743759 TI - Effect of energy-restricted diet on sympathetic muscle nerve activity in obese women. AB - Twenty obese women aged 45-65 years with borderline hypertension were allocated randomly to either a group with an energy-restricted diet or to a control group. Body weight, blood pressure, urinary sodium, and urinary excretion of norepinephrine and plasma volume were recorded. Resting muscle sympathetic nerve activity was measured in the peroneal nerve by tungsten microelectrodes and expressed as bursts per minute. These measurements were repeated after 3 days of semistarvation and after a body weight reduction of 7% while each patient's weight was in a steady state. After 3 days of semistarvation, only body weight was reduced, whereas after the long-term energy intake restriction, there were reductions of body weight (79.9 +/- 3.4 versus 74.1 +/- 3.4 kg; p less than 0.001), diastolic blood pressure (93 +/- 3 versus 86 +/- 4 mm Hg; p = 0.01), and muscle sympathetic nerve activity (49 +/- 2 versus 42 +/- 3 bursts/min; p less than 0.05). Other variables were unchanged. There were no changes in body weight, blood pressure, or muscle sympathetic nerve activity in the control group. We conclude that body weight decrease in obesity results in a reduction of blood pressure that is at least partially caused by a reduction of sympathetic vasoconstrictor activity. PMID- 1743760 TI - Effects of acute carbohydrate administration on central and peripheral hemodynamic responses to mental stress. AB - Essential hypertension is closely related to conditions with impaired glucose tolerance and hyperinsulinemia. To evaluate a possible interaction between the sympathetic nervous system and carbohydrate ingestion on the circulatory responses to psychosocial stress, we compared the hemodynamic effects of an oral glucose challenge with those observed after placebo in 10 glucose-tolerant, normotensive young men at rest and during standardized mental stress. After glucose, resting cardiac output increased by 20% (p less than 0.05), which was mainly due to an increased heart rate (+14%; p less than 0.001). Since total peripheral resistance decreased by 13% (p less than 0.02), mean arterial pressure was unaffected by glucose. In spite of this, glucose loading was associated with a slight increase in systolic blood pressure and a gradual decrease of diastolic blood pressure. Resting forearm blood flow was unaffected by glucose. The stress response after placebo was characterized by the expected increase in cardiac output and mean arterial pressure, and an unchanged total peripheral resistance. By contrast, in the postprandial state the pressor response to stress was solely dependent on an increased systemic vascular resistance, and cardiac output was unaffected by stress. After glucose, the stress-induced muscular vasodilation in the forearm was reduced to 40% of that observed after placebo (p less than 0.01). Thus, acute carbohydrate administration has significant hemodynamic effects in humans. Furthermore, during the postprandial period there is a marked alteration of the pattern of the circulatory responses to psychosocial stress, characterized by attenuated muscular vasodilation and a rise in systemic vascular resistance. PMID- 1743761 TI - Abnormal renal hemodynamics in black salt-sensitive patients with hypertension. AB - African-Americans with essential hypertension are more prone to the development of renal failure and are frequently salt-sensitive as well. Because alterations of intrarenal hemodynamics are important in the progression of renal disease and because salt-sensitive animal models with hypertension manifest a greater propensity to develop glomerulosclerosis in association with a rise in glomerular capillary pressure, we tested whether the renal hemodynamic adaptation to high dietary Na+ intake differs in salt-sensitive and salt-resistant hypertensive patients. We studied 17 black and nine white patients with essential hypertension who were placed on a low Na+ diet (20 meq/day) for 9 days, followed by a high Na+ diet (200 meq/day) for 14 days. During the last 4 days of each diet regimen, they received 30 mg/day of slow-release nifedipine. Eleven blacks were salt-sensitive, and all whites were salt-resistant. During the low Na+ diet period, salt sensitive and salt-resistant patients had similar mean arterial pressure, glomerular filtration rate, effective renal plasma flow, and filtration fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743762 TI - Sodium excretion and racial differences in ambulatory blood pressure patterns. AB - The influence of Na+ excretion and race on casual blood pressure and ambulatory blood pressure patterns was examined in a biracial sample of healthy, normotensive children and adolescents (10-18 years; n = 140). The slopes relating 24-hour urinary Na+ excretion to systolic blood pressure were different for both black and white subjects for casual blood pressure (p less than 0.001) and blood pressure during sleep (p less than 0.03). For casual blood pressure, the slope was significant for black subjects (beta = 0.17; p less than 0.001) but not for white subjects. For blood pressure during sleep, the slope was again significant for black subjects (beta = 0.08; p less than 0.01) but not for white subjects. Na+ excretion was also related to awake levels of systolic blood pressure for black subjects (beta = 0.08, r = 0.36; p less than 0.01), although the slopes for both black and white subjects were not significantly different. Further analyses indicated the results were not due to racial differences in 24-hour urinary K+ excretion. However, plasma renin activity was marginally related to Na+ excretion in white subjects (r = 0.22; p less than 0.06) but not black subjects, a finding that is consistent with previous studies. Na+ excretion was not associated with diastolic blood pressure or heart rate in either group under any condition. The results of this study support research that has demonstrated a stronger relation between Na+ handling and casual blood pressure in black subjects and extend these findings to blood pressure while the subject is both awake and asleep. PMID- 1743763 TI - Mutagenicity study of urine from smoking and non-smoking road tanker drivers. AB - Urine from 32 road tanker drivers handling petrol, diesel, paraffin and white spirit was tested in the Salmonella/microsome mutagenicity system using tester strains TA98 anbd TA100. Urine samples were collected before and after tanking and were concentrated 250-fold on XAD-2 columns before testing. Controls were 33 office employees from the same plant. No effect on urinary mutagenicity of occupational exposure to petroleum products was found. Significant differences in mutagenic effect were demonstrated between smokers and non-smokers. Methodological experiments demonstrated a dose/response effect of smoking on urinary mutagenicity. A modified test using a preincubation period and an increased concentration of bacteria was more sensitive than the standard Ames test to mutagens from tobacco smoking. PMID- 1743764 TI - Indoor climate and air quality in new offices: effects of a reduced air-exchange rate. AB - In response to a request from the personnel of a credit bank that had been moved into a new building, an evaluation was made of employee health complaints. The prevalence of symptoms was determined using a self-administered questionnaire. Ventilation effectiveness, contaminant concentrations (which included chemicals and bioaerosols) and microclimate were studied to establish their relationship to environmental discomfort and to the health problems mentioned by the employees. Indoor air quality--which was assessed in different seasons--revealed relatively high levels of carbon dioxide and bioaerosols in areas occupied by employees as compared with other places. Temperature and humidity were considered to be satisfactory. Although a causative agent was not isolated, the authors conclude that an ineffective rate of room air exchange, possibly in interaction with chemical contaminants, may be responsible for the discomfort and, perhaps, for the health symptoms experienced by workers in fully enclosed rooms. PMID- 1743765 TI - Work load and physiological responses during asbestos removal with protective clothing. AB - The removal of asbestos-containing building materials requires the use of dust repelling protective clothing and a respirator. The present study was aimed at measuring physiological responses to asbestos removal in actual work situations. The subjects were eight asbestos workers. During the work, the men wore permeable or impermeable clothing along with a powered or non-powered filtering device including a full-face or half-face mask. Environmental parameters, work postures, heart rate (HR), the skin temperature at two sites and the rectal temperature were recorded every minute during work. Perceived exertion, thermal sensation, thermal comfort, and skin wetness were rated by the subjects. The ambient temperature at work sites ranged from 19 degrees to 37.5 degrees C and relative humidity, from 21% to 50%. The mean HR ranged from 101 to 141 beats min-1. The calculated (from HR measurements) average oxygen consumption (VO2) varied from 0.9 to 1.9 l min-1, which corresponded to 27%-60% of the maximal value. The peak rectal temperature and the highest mean of two measurements of skin temperature were 37.7 degrees +/- 0.3 degree C and 34.4 degrees +/- 0.9 degree C, respectively. The sweat rate varied from 162 to 583 g h-1. Poor work posture was common during asbestos removal. The arms were elevated over shoulder level for 35% of the work time. During the work the mean physiological strain was considered to be moderate, with some heavy peak loads being registered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743766 TI - Correlation of levels of volatile versus carcinogenic particulate polycyclic aromatic hydrocarbons in air samples from smokehouses. AB - In the present study, data on the concentration of polycyclic aromatic hydrocarbons (PAH) in air samples from fish smokehouses (Nordholm et al. 1986) and meat smokehouses (Hansen et al. submitted for publication) were used to analyze the extent to which six different volatile PAH compounds could function as markers for the total concentration of six different carcinogenic particulate PAH compounds. Although a significant positive correlation was observed between the concentration of each of six volatile compounds and the total concentration of carcinogenic PAH compounds, a particularly good correlation was observed for phenanthrene, anthracene, fluoranthene and pyrene. Calculations of the sensitivity, specificity, positive predictive value and negative predictive value of these potential markers revealed that naphthalene and phenanthrene exhibited the highest sensitivity as markers for total carcinogenic PAH compounds in air samples from smokehouses, whereas fluoranthene and pyrene displayed the highest specificity. However, when the applicability of the six markers was tested on air samples from iron foundries, only naphthalene and pyrene were useful as markers for the carcinogenic compounds. The present study indicates that naphthalene and pyrene might function as markers for carcinogenic PAH compounds, that are present at low concentrations and are therefore difficult and time-consuming to measure directly. PMID- 1743767 TI - Acute effects of transient vertical whole-body vibration. AB - The question as to whether shock-type whole-body vibration causes increasingly acute strain was investigated. Random vibrations were superimposed with shocks differing in amplitude and in number per unit of time in a systematic manner. The weighted root mean square (rms) acceleration was kept constant in all over the varied experiments. A total of 17 men were exposed to vibration from an electrohydraulic simulator. The following strain criteria were used: biodynamic behavior of the trunk and the head, electrical activity of the muscles of the back and the neck, subjective sensation, skin temperature in the lumbar area and visual and tracking performance. It was found that increasing shock amplitude and, in some experiments, also increasing numbers of shocks led to increasingly acute effects that varied, depending on the kind of shock used. New methods should be developed for the assessment of transient vibration that are better than the existing standards. PMID- 1743768 TI - Carpal tunnel syndrome: role of occupation. AB - A total of 21 consecutive patients who underwent surgery for carpal tunnel syndrome in a regional hospital were analysed for their trade and serum alpha 1 antitrypsin phenotypes. The majority of these cases were women and mostly manual trades and professions were involved. Furthermore, heterozygous antitrypsin phenotypes were more frequent among the surgical cases than among the general Swiss population. In a second stage, the incidence of carpal tunnel syndrome in Switzerland was studied for 1 year from June 1988 through May 1989 using the sentinel system developed by the Federal Office of Public Health Administration. In all, 188 cases were found, most of whom were women, which was compatible with the frequency in other countries. A complementary questionnaire that was filled out by 65 cases and their matched controls showed that housewives and shop clerks were overrepresented among the patients. Likewise, exposure to vibrating tools and frequent extensions and/or flexions of the wrist were mentioned more often by the cases than by the controls. The present study confirms previous findings that women are at greater risk of developing carpal tunnel syndrome especially in jobs requiring repetitive movements or operation of vibrating tools. A constitutional element in pathogenesis was suggested by observations that the mothers of the cases had often also been afflicted with carpal tunnel syndrome and that the frequency of distribution of antitrypsin phenotypes in patients differed from that in the general population. PMID- 1743769 TI - An epidemiological study of cancer risk among workers exposed to ethylene oxide using hemoglobin adducts to validate environmental exposure assessments. AB - Cancer morbidity was investigated in a cohort of 2,170 ethylene oxide (EO) exposed workers from 2 plants producing disposable medical equipment. The subjects had been employed for at least 1 year during the periods 1970-1985 and 1964-1985, respectively. The exposure to EO was assessed for each of six job categories in the plants with respect to each calendar year, on which basis values for individual cumulative exposure to EO (ppm-years) were calculated. The levels of hydroxyethyl adducts to N-terminal valine (HOEtVal) in hemoglobin fitted well with the values estimated for airborne exposure to EO. No increased cancer incidence was found [standardized morbidity ratio (SMR), 0.78; 95% CI, 0.49-1.21)]. No leukemia was observed, but one case of non-Hodgkin's lymphoma, one case of myeloma, and one case of polycythemia vera were diagnosed as compared with two expected hematopoietic and lymphatic tumors (SMR, 1.54; 95% CI, 0.32 4.5). No stomach cancer was detected as compared with the 0.5 case expected. There were no significant exposure-response associations between estimates of exposure to EO and cancer morbidity. PMID- 1743770 TI - Effect of simultaneous exposure to toluene and xylene on their respective biological exposure indices in humans. AB - Studies that specifically address the influence of controlled human exposure to a combination of solvents on the biological monitoring of exposure are limited in number. The present study was undertaken to investigate whether simultaneous exposure of human volunteers to toluene and xylene could modify the respective metabolic disposition of these solvents. Five adult Caucasian men were exposed for 7 consecutive h/day over 3 consecutive days to 50 ppm toluene and 40 ppm xylene either separately or in combination in a dynamic, controlled exposure chamber (low-level exposure). The experiment was repeated three times at intervals of 2 weeks. In another experiment, three subjects were exposed to 95 ppm toluene and 80 ppm xylene or a combination of both for 4 h (high-level exposure). The concentration of unchanged solvents in blood (B) and in end exhaled air (EA) as well as the urinary excretion of hippuric acid (HA) and methylhippuric acids (MHAs) were determined. Simultaneous exposure to the lowest level of solvents did not alter the concentration of unchanged solvents in blood or in exhaled air (average of 3-weekly means; single vs mixed exposure at 6.5 h exposure): B-toluene, 77.1 vs 78.1 micrograms/100 ml; B-xylene, 67.6 vs 77.8 micrograms/100 ml; EA-toluene, 9.9 vs 9.5 ppm; EA-xylene, 5.3 vs 4.8 ppm. Similarly, mixed exposure did not modify the excretion of urinary metabolites during the 3- to 7-h exposure period: HA, 1.11 vs 1.11 g/g creatinine: MHAs, 0.9 vs 0.87 g/g creatinine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743771 TI - Dose-dependent increase in 2,5-hexanedione in the urine of workers exposed to n hexane. AB - The concentrations of 2,5-hexanedione (2,5-HD), an n-hexane metabolite, and 2 acetylfuran (2-AF) were measured in urine samples from 123 workers who had predominantly been exposed to n-hexane vapor and 53 workers who had experienced no exposure to solvents. The time-weighted average intensity of exposure to n hexane vapor was determined by a diffusive sampling method. For biological monitoring of exposure, urine samples were collected late in the afternoon during the second half of a working week and were analyzed in the presence and absence of acid hydrolysis (at pH less than 0.5) for 2,5-HD and 2-AF by gas chromatography on a nonpolar capillary DB-1 column. The urinary 2,5-HD concentration increased as a linear function of the intensity of exposure to n hexane, showing a correlation coefficient of 0.64-0.77 after acid hydrolysis and that of 0.73-0.83 in the absence of hydrolysis, depending on the correction for urinary density (P less than 0.01 in all cases, with no improvement in the coefficient occurring after the corrections). In contrast, 2-AF levels were independent of n-hexane exposure. The geometric mean 2,5-HD concentration in urine samples from 53 nonexposed men was 0.26 mg/l as observed (i.e., with no correction), 0.19 mg/l after correction for a urinary specific gravity of 1.016, and 0.23 mg/g creatinine after correction for creatinine concentration, and the geometric standard deviation was approximately 2. PMID- 1743772 TI - Study on suspended particulate matter and polycyclic aromatic hydrocarbons in indoor and outdoor air. AB - To study changes in the concentration of suspended particulate matter (SPM) in indoor and outdoor air, a new portable sampler (AND sampler) was designed that could separately collect particles exhibiting aerodynamic diameters of greater than 10 microns, 2-10 microns, and less than 2 microns. The relationship between the airborne particle concentration in indoor air and that in outdoor air varied with the aerodynamic diameter of the particles. The concentration of SPM in the indoor air increased in proportion to that in the outdoor air. The concentration of polycyclic aromatic hydrocarbons (PAH) in SPM also varied with the aerodynamic diameter of the particles. Fine particles exhibiting an aerodynamic diameter of less than 2 microns contained high concentration of PAH. The concentrations of benzo(k)fluoranthene, benzo(a)pyrene, and benzo(ghi)perylene in indoor air increased in proportion to those in outdoor air. PMID- 1743773 TI - The influence of climatic conditions on the heat balance of the human body. AB - The structure of heat exchange between the human body and its surroundings has been studied according to M.I. Budyko's model. Comparative measurements were carried out in the Polish Lakeland (maritime, temperate warm climate), in Central Mongolia (continental, temperate cool climate), and in the Kara Kum desert (dry subtropical climate). The results deal with the summer and early autumn seasons. The calculations indicate that the quantitative apportionment of various forms of heat exchange depend on specific weather conditions, which are typical for the distinguished climatic zones. PMID- 1743774 TI - Effects of cold stress on glutathione and related enzymes in rat erythrocytes. AB - Effects of acute and chronic cold stress on glutathione and related enzymes in rat erythrocytes were investigated. Blood from both cold-acclimated (CA) and cold adapted (CG) rats had significantly lower concentrations of glutathione than blood from control animals. Superoxide dismutase activity was increased significantly in CA rats and tended to rise in CG rats. Activity of glutathione peroxidase in erythrocytes was inconsistent in that it tended to increase in CA rats but decreased significantly in CG rats. The results may imply that CG rats suffered deleterious effects of hydrogen peroxide. On the other hand, there were marked decreases in glutathione peroxidase and glutathione reductase activities in acutely cold-exposed rats in conjunction with unchanged levels of glutathione. In all treatments the state of riboflavin metabolism was estimated to be adequate, since no increases were observed in the erythrocyte glutathione reductase activity coefficient. PMID- 1743775 TI - Productivity of pure- and crossbred cattle in a subtropical environment. AB - The influence of different breeds of sire and dam types on cow productivity in an arid, subtropical environment was studied. Cows with calves sired by Simmentaler, Hereford and Bonsmara bulls were more (P less than 0.05) productive than those with calves sired by Afrikaner bulls. Simmentaler sires were superior (P less than 0.05) to Bonsmara sires. Crossbred cows of predominant (greater than 50%) Bos taurus breeding were generally superior to crossbreds of predominant B. indicus breeding and purebreds. Crossbreeding systems to utilize breed effects to optimise cow productivity within environmental constraints are discussed. PMID- 1743776 TI - Effect of chronic microwave radiation on T cell-mediated immunity in the rabbit. AB - Experiments were conducted to elucidate the effects of chronic low power-level microwave radiation on the immunological systems of rabbits. Fourteen male Belgian white rabbits were exposed to microwave radiation at 5 mW/cm2, 2.1 GHz, 3 h daily, 6 days/week for 3 months in two batches of 7 each in specially designed miniature anechoic chambers. Seven rabbits were subjected to sham exposure for identical duration. The microwave energy was provided through S band standard gain horns connected to a 4K3SJ2 Klystron power amplifier. The first batch of animals were assessed for T lymphocyte-mediated cellular immune response mechanisms and the second batch of animals for B lymphocyte-mediated humoral immune response mechanisms. The peripheral blood samples collected monthly during microwave/sham exposure and during follow-up (5/14 days after termination of exposures, in the second batch animals only) were analysed for T lymphocyte numbers and their mitogen responsiveness to ConA and PHA. Significant suppression of T lymphocyte numbers was noted in the microwave group at 2 months (P less than 0.01, delta % 21.5%) and during follow-up (P less than 0.01, delta % 30.2%). The first batch animals were initially sensitised with BCG and challenged with tuberculin (0.03 ml) at the termination of microwave irradiation/sham exposure and the increase in foot pad thickness (delta mm), which is a measure of T cell mediated immunity (delayed type hypersensitivity response, DTH) was noted in both the groups. The microwave group revealed a better response than the control group (delta % +12.4 vs. +7.54). The animals were sacrificed and the tissue T lymphocyte counts (spleen and lymph node) were analysed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743777 TI - Seasonal energy requirements and thermoregulation of growing pouched mice, Saccostomus campestris (Cricetidae). AB - Pouched mice (Saccostomus campestris) were born in captivity during January and March and subsequently maintained under long photoperiod (14 h light: 10 h dark) at 25 degrees C. During their first winter (July) and the following summer (January) the pouched mice were exposed to natural photoperiod in an unheated laboratory for 3 weeks prior to measurement. The pouched mice continued to grow during the study, and were significantly heavier after summer exposure than after winter exposure 6 months earlier. Although this increase in body mass would result in a decline in their surface area to volume ratio there was no significant decline in minimal thermal conductance (Cm) and winter-exposed pouched mice had a relatively lower Cm than expected. Meanwhile the smaller, winter-exposed animals displayed a significantly higher capacity for non shivering thermogenesis, together with higher levels of basal metabolism than summer individuals. These differences were not solely attributable to the contrasting body mass of each group and it is therefore clear that S. campestris can increase thermoregulatory heat production, and modify heat loss following exposure to short photoperiod and cold during their first winter. Despite the significant increase in metabolism, the overall energy requirements of small, winter-exposed animals were significantly lower than those for heavier pouched mice following exposure to summer conditions. These results suggest that growing pouched mice can effectively adapt to lower temperature conditions during their first winter, yet accrue considerable overall savings in total energy requirements as a result of their smaller body mass. PMID- 1743778 TI - Is calcium excess in western diet a major cause of arterial disease? AB - The daily requirement of a young adult for calcium is 300-400 mg, the quantity consumed in many third-world countries. The dietary intake can be doubled or trebled by consumption of milk, thus half a litre of milk, consumed by many individuals daily in prosperous countries, adds 600 mg. The need for calcium is greatly reduced in old age, so that the excess from a given intake becomes more pronounced. The potential hazard of a high intake is that a small fraction finds its way into soft tissues. The aorta is notably prone to calcification, resulting in loss of elasticity. The aorta and its large branches constitute an elastic reservoir, distended during systole and contracting in diastole. This contraction provides the energy for the maintenance of diastolic pressure, which decreases with the deterioration of elasticity and needs a continually increasing systolic pressure to restore its normal value. The heart is disadvantaged in two ways. Its work is increased by having to eject the systolic volume into a stiffer reservoir, and the diastolic filling of the coronary arteries is reduced. This is the main cause of hypertension in old age--there is no increase in blood pressure with age in undeveloped countries where intake of calcium is low. The best cure would be prevention: the reduction of intake of calcium in prosperous countries. Failing that, phytic acid is suggested as the best calcium antagonist. Phytic acid, a natural product present in grains, converts dietary calcium into insoluble phosphates which pass unabsorbed through the digestive tract. The presently used calcium antagonists are not so satisfactory. PMID- 1743779 TI - Advances in cardiac surgery in the last decade. PMID- 1743780 TI - Permanent cardiac pacing in children: morbidity and efficacy of follow-up. AB - The data from 50 permanently paced children [mean standard deviation follow-up 5.3 +/- 3.7 years] were reviewed, with special attention being paid to the cause of complications and the efficacy of follow-up. The 5-year survival (SD) of the patients was 78 +/- 6%; mortality was mainly due to the underlying cardiac disease. The 5-year survival (SD) of the pacing systems was 48 +/- 8%. Surgical interventions were necessary every 4.9 patient years. Of these interventions, 58% were caused by lead-related problems. Epicardial leads showed significantly more exit blocks and high thresholds than endocardial leads. Endocardial leads, therefore, should be used at a younger age than is now the current practice, from 5 years of age onwards, for example. If epicardial leads are used, the pacemaker must have a high output facility. Since exit block occurred only within the first 3 months after implantation, we suggest frequent transtelephonic monitoring during the first 3 months. Holter monitoring appeared to be the most effective and sensitive method of detecting malsensing and should be performed regularly. PMID- 1743781 TI - Effects of prostaglandin E1 given in low doses on the histopathology of the arterial duct. AB - The histopathology of the arterial duct was studied in relation to the maximal infusion rate of prostaglandin E1 administered in 35 infants with congenital heart disease. Two groups were distinguished based on the maximal infusion rate. The group receiving prostaglandin at low dose received 0.01 to 0.05 micrograms/kg/min (16 cases), the group having a high dose received greater than 0.05 to 0.7 micrograms/kg/min (19 cases). The histopathology was compared between the groups. Ductal damage was less common in the cases receiving a low rate of infusion than in those having a high rate of infusion. Multivariate analysis showed no relation between ductal pathology and the age of onset or duration of treatment, nor on the total dose of prostaglandin E1. Histological abnormalities were more common in patients with a gestational age equal to or greater than 40 weeks. Ductal damage was less common in patients with pulmonary atresia or stenosis compared with other anatomic diagnoses. Low dose infusions are recommended for treatment with prostaglandin E1 in infants with congenital heart disease. PMID- 1743782 TI - Familial dilated cardiomyopathy: a transverse and longitudinal clinical and echocardiographic study. AB - The familial occurrence of hypertrophic cardiomyopathy is well known; familial dilated cardiomyopathy has so far received less attention. Ten families with two or more members affected by dilated cardiomyopathy were studied by echocardiography. In 3 out of 10 families, a transverse study extended to even apparently healthy subjects was carried out, which included a total of 45 subjects. In 19 out of the 45, dilated cardiomyopathy (either symptomatic or asymptomatic) was diagnosed at echocardiography. Three more relatives, already dead of the disease, were identified through hospital records. A clinical and echocardiographic longitudinal study, lasting up to 11 years, was carried out in 5 of the 10 families. During the follow-up, 8 out of 19 patients who, at first examination were affected by dilated cardiomyopathy, died, one improved, 3 remained in stable condition and 7 were lost at follow-up. One of two patients who presented echocardiographic findings suggestive of border-line dilated cardiomyopathy returned to normality and the other developed dilated cardiomyopathy. The clinical and echocardiographic findings in our patients, and in their relatives, suggest the possibility that idiopathic dilated cardiomyopathy may be a multifactorial disease in which genetic factors might play a variable role. PMID- 1743783 TI - Symptom-limited, self-paced walking in the assessment of cardiovascular disease in patients with and without heart failure: the predictive value of clinical, anthropometric, echocardiographic and ergonometric parameters. AB - The assessment of functional capacity in heart disease remains problematic, and it is unclear whether maximal exercise testing is physiologically reflective of the activities of daily living or the quality of life. We therefore employed a symptom-limited, self-paced walking protocol to assess the physical conditions of 41 Nigerian cardiac patients, with and without heart failure. The walking time, walking speed and distance as well as the energy expenditure (Kcal.min-1) were markedly reduced (P less than 0.001) in patients with heart failure (n = 26) compared to the cardiac patients not in failure (n = 15). The double product corrected for exercise time (an index of myocardial oxygen use) was, however, significantly higher (P less than 0.001) in the group with heart failure. Using multiple regression analysis, the parameters of self-paced walking capacity (distance, walking time, and speed) could reliably be predicted (r2 greater than 0.9) from age, body surface area, energy expenditure, and echocardiographic left ventricular dimension in the patients without heart failure. The presence of heart failure appeared to weaken the predictability of the regressions. A significant correlation was obtained between the self paced exercise time and the Bruce protocol treadmill time (r2 = 0.91, P = 0.004) in a subgroup of the patients with heart failure. Thus, the self-paced walking test is sensitive to changes in congestive heart failure and the exercise capacity can be predicted from age and biophysical parameters. The wider clinical usage of this modality, especially in frail patients, is hereby recommended. PMID- 1743784 TI - Low-dose simvastatin for the treatment of hypercholesterolaemia in recipients of cardiac transplantation. AB - There is increasing evidence that hypercholesterolaemia is an important contributor to the development of accelerated coronary arterial disease in the cardiac allograft. The optimal drug therapy of hypercholesterolaemia in recipients after cardiac transplantation, however, has not been defined. Simvastatin (an inhibitor of hydroxy-methyl glutaryl-coenzyme A reductase), at a dose of 10 mg/day, was administered to 12 recipients with serum total cholesterol greater than or equal to 7.8 mmol/l and serum triglyceride less than or equal to 4.5 mmol/l refractory to dietary measures during a follow-up period of 1-5 years after cardiac transplantation. All patients received maintenance doses of cyclosporin A and, in some instances, azathioprine and prednisolone. After 2 months treatment with simvastatin, serum total cholesterol was significantly reduced from 8.8 +/- 0.3 mmol/l (mean +/- SEM) to 5.5 +/- 0.5 mmol/l, P less than 0.001, low density cholesterol from 6.6 +/- 0.4 to 3.8 +/- 0.3 mmol/l, P less than 0.001 and triglycerides from 2.4 +/- 0.2 mmol/l to 1.8 +/- 0.2 mmol/l, P less than 0.005. These changes were maintained after a period of treatment of 8 months. Serum high density cholesterol, hepatic transaminase levels, serum creatinine, creatine kinase and cyclosporin A blood levels were not altered by treatment with simvastatin. It is concluded that, in this study group, low-dose simvastatin appears to be well tolerated and has favourable lipid modifying properties. PMID- 1743785 TI - Indoor passive smoking: its effect on cardiac performance. AB - We studied 19 nonsmoker male volunteers, 9 healthy (mean age 30.5 +/- 8.5), and 10 with previous myocardial infarction (mean age 53.8 +/- 5.3), who underwent exercise stress testing twice: in a smoke-free environment and in a smoking environment (carbon monoxide concentration 30-35 ppm). We measured peak exercise power, time to recovery of pre-exercise heart rate, expired concentration of carbon monoxide and plasma carbon monoxide. Obtained data were compared by using t-test. P less than 0.05 was statistically significant. Mean data observed in healthy people were as follows. Peak exercise power 220 +/- 30 watts in a smoking environment versus 220 +/- 30 in a smoke-free environment (P greater than 0.05). Time to recovery of pre-exercise heart rate 19 +/- 4 minutes in a smoking environment versus 8.5 +/- 4 in a smoke-free environment (P less than 0.01). Expired concentration of carbon monoxide before exercise 2.3 +/- 2.01 ppm versus 8.5 +/- 1.6 (P less than 0.01) after exercise in a smoking environment, and 2.3 +/- 2 ppm before exercise versus 2.1 +/- 1.9 after exercise in a smoke-free environment (P less than 0.05). Plasma carbon monoxide before exercise 1.4 +/- 0.2% versus 1.7 +/- 0.4 after exercise in a smoking environment (P greater than 0.05), and 1.2 +/- 0.4% before exercise versus 1.2 +/- 0.4 in a smoke-free environment (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743786 TI - Acute aortitis and aortic incompetence due to systemic rheumatological disorders. AB - We report the clinical, laboratory and echocardiographic features of five cases of aortic incompetence associated with ankylosing spondylitis, rheumatoid arthritis and undefined connective tissue diseases. Immunosuppression with steroids and cytotoxic agents was used to suppress aortic root inflammation in four cases; in three the aortic root size stabilized and the patients remain well with no evidence of increasing aortic incompetence. In one case, control of the inflammatory process was never fully achieved for any length of time and the patient died shortly after aortic valve replacement. A fifth case required urgent valve replacement and remains well. A systemic rheumatological disorder should be considered in cases of apparent "lone" aortic incompetence and conversely aortic incompetence should not be overlooked in established systemic rheumatological disease. Immunosuppressive therapy may prevent or delay the need for aortic valve replacement in such cases. PMID- 1743787 TI - The role of captopril as single therapy in hypertension and angina pectoris. AB - Eighteen hypertensive patients with a resting diastolic blood pressure between 100 and 120 mmHg who also had angina and proven coronary arterial disease entered a dose titration study to evaluate the efficacy of captopril as a single therapy in hypertension and coexisting stable angina. Captopril was administered for 2 weeks at 25 or 50 mg three times daily and the patients evaluated subjectively and by maximal symptom limited treadmill exercise testing. In comparison to placebo captopril 25 mg and 50 mg dosage increased time to 1 mm ST depression from 188.2 +/- 24.4 sec on placebo to 337.6 +/- 29.5 and 364.2 +/- 36.2 sec respectively (P less than 0.01). The maximum ST segment depression was reduced from 2.5 +/- 0.25 mm on placebo to 1.4 +/- 0.22 mm on captopril 25 mg and 1.2 +/- 0.30 mm on captopril 50 mg (P less than 0.01). Exercise duration increased from 310.3 +/- 21.4 sec on placebo to 438.3 +/- 27.3 sec on captopril 25 mg and to 460.9 +/- 26.5 sec on captopril 50 mg (P less than 0.01). The resting systolic blood pressure decreased from 184.1 +/- 4.7 mmHg on placebo to 159 +/- 4.2 mmHg on captopril 25 mg and to 150.9 +/- 4.6 mmHg on captopril 50 mg (less than 0.01). Similarly, diastolic blood pressure decreased from 111.6 +/- 2.1 mmHg on placebo to 93.8 +/- 1.3 mmHg on captopril 25 mg and to 90.0 +/- 1.7 mmHg on captopril 50 mg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743788 TI - Noninvasive determination of the left ventricular end-systolic pressure. AB - To find a noninvasive method for estimating left ventricular end-systolic pressure, 40 patients were studied during cardiac catheterization. Arterial pressure was taken directly from the ascending aorta. Carotid pulse tracing and measurement of blood pressure by cuff sphygmomanometry were taken simultaneously. The tracings were calibrated and left ventricular end-systolic pressure was estimated directly and indirectly. Simple linear regression analysis gave the equations: (1) left ventricular end-systolic pressure direct = 0.56 left ventricular end-systolic pressure indirect + 43.8 (r = 0.61, P = 0.00004), and (2) left ventricular end-systolic pressure direct = 0.39 systolic arterial pressure indirect + 48.8 (r = 0.62, P = 0.00002). To test the accuracy of the technique the study was continued in 40 patients. Left ventricular end-systolic pressure was also estimated by the 2 equations. Left ventricular end-systolic pressure direct was correlated with left ventricular end-systolic pressure estimated by the 2 equations and there was no statistical difference. This noninvasive technique is a bedside method for clinical measurement of left ventricular end-systolic pressure. PMID- 1743789 TI - Left ventricular volumes and function immediately after balloon mitral valvoplasty. AB - To evaluate acute changes in left ventricular volumes and function immediately after successful percutaneous balloon mitral valvoplasty, twenty young patients with isolated rheumatic mitral stenosis (male 9, female 11, mean age 22 +/- 6 years) were studied. The area of the orifice of the mitral valve following valvoplasty, increased from 0.97 +/- 0.27 cm2 to 2.46 +/- 0.75 cm2 (P less than 0.001). No significant change was observed in left ventricular end-diastolic volumes (117 +/- 27 ml to 119 +/- 29 ml, P greater than 0.10), end-systolic volumes (51 +/- 21 ml to 50 +/- 20 ml, P greater than 0.10), ejection fraction (0.57 +/- 0.10 to 0.58 +/- 0.10, P greater than 0.10) and left ventricular meridian wall stress (68 +/- 20.10(3) dynes/cm2 to 65 +/- 14, P greater than 0.10) immediately after valvoplasty. There was no acute change in heart rate, left ventricular end-diastolic pressure, cardiac index and grade of mitral regurgitation. Patients with depressed left ventricular ejection fraction (less than or equal to 0.55, n = 10) and those with normal ejection fraction (greater than 0.55, n = 10) had similar baseline left ventricular end-diastolic volumes and showed no significant change in volumes and ejection fraction after the procedure, although the former group had a greater orificial area after valvoplasty (P less than 0.05). We conclude that an acute increase in the orifice of the mitral valve in patients with rheumatic mitral stenosis is not associated with any significant change in left ventricular volumes and function. PMID- 1743790 TI - Pathogenesis of various forms of double outlet right ventricle in mouse fetal trisomy 13. AB - The pathogenesis of double outlet right ventricle with or without pulmonary infundibular atresia in mouse fetal trisomy 13 was studied at the organ level using microdissection and scanning electron microscopy. Altogether, 394 karyotyped trisomic embryos were collected between 11 days and 16 hours of gestation (presence of a vaginal plug = day 1) and 15 days of gestation at intervals of 8 hours, and at 16 days of gestation. The hearts were perfusion fixed, microdissected, and prepared to be observed in scanning electron microscope in the following standardized orientations: frontal, right or left profile, septal and parietal halves of the right ventricle and outflow tract (conotruncus). Comparison of 276 trisomic hearts with their normal counterparts described previously has shown that: the first pathognomonic feature is the abnormal anterior position of the proximal part of the parietal outflow tract ridge or of both ridges (at 12 days and 16 hours of gestation); the abnormal anterior fusion of these ridges ("coalescence") results in a mesenchymal mass behind which is deviated the pulmonary part of the outflow tract lumen; from 14 days and 16 hours of gestation on, this lumen is either obstructed, resulting in a supravalvar stenosis of the pulmonary trunk and subsequently evolving into double outlet right ventricle with pulmonary infundibular atresia; or, in a minority of cases, this lumen is not obstructed and the heart develops into double outlet right ventricle without pulmonary infundibular atresia. The pathogenesis of these malformations differs from most of the known hypotheses based on deductions from human malformed hearts, as well as from observations of the pathogenesis of similar outflow tract malformations, such as those found in the Keeshond dog or rats treated with trimethadione. PMID- 1743791 TI - Functional tricuspid regurgitation following replacement of the mitral valve. AB - In this series, the effect of replacement of the mitral valve was examined in 86/900 (9.6%) patients who had developed moderate functional tricuspid regurgitation, secondary to rheumatic mitral valvar disease. These patients were subdivided according to the severity of pulmonary hypertension and impairment of right ventricular function. Forty-six patients presented with severe pulmonary hypertension and 40 patients had moderate pulmonary hypertension (mean main pulmonary arterial pressure: 78 +/- 14 mmHg vs 41 +/- 6 mmHg; P less than 0.05). The latter had more advanced disease, greater impairment of right ventricular function and dilatation of the right heart chambers. Functional tricuspid regurgitation regressed in 38/42 survivors with severe pulmonary hypertension and persisted or progressed significantly in 22/34 survivors with impaired right ventricular function despite successful replacement of the mitral valve. The latter underwent replacement of the tricuspid valve (n = 16) or tricuspid annuloplasty (n = 6), at a mean interval of 44 +/- 4.4 months after replacement of the mitral valve, which resulted in 8/22 (23.5%) early deaths. Functional tricuspid regurgitation is more likely to persist in patients with advanced right ventricular failure. Tricuspid valvar competence should be restored in these patients at initial replacement of the mitral valve. PMID- 1743792 TI - Anomalous origin of the left pulmonary artery from the ascending aorta in a patient with tetralogy of Fallot and "absent pulmonary valve". AB - The rare association of tetralogy of Fallot, rudimentary formation of the leaflets of the pulmonary valve, and anomalous origin of the left pulmonary artery from the ascending aorta is described in a two-month-old infant. The diagnosis was made by cardiac catheterisation and angiography. PMID- 1743793 TI - Fatal myocardial infarction in hypertrophic cardiomyopathy associated with non penetrating chest trauma. AB - Myocardial infarction as a result of injury to the coronary arteries is a rare complication of non-penetrating chest trauma. We report a case of fatal inferior wall myocardial infarction following traumatic injury to the right coronary artery, complicated by atrioventricular dissociation, in a patient with a combination of hypertrophic cardiomyopathy and non-occlusive coronary artery disease. PMID- 1743794 TI - Cardiogenic shock due to neoplastic infiltration of cardiac muscle. AB - We present a patient with cardiogenic shock resulting from extensive neoplastic infiltration of the inferolateral left ventricular cardiac muscle by an epidermoid carcinoma of the lower third of the oesophagus. PMID- 1743795 TI - Anteroseptal myocardial infarction clinically mimicking right ventricular infarction. AB - Acute transmural anteroseptal myocardial infarction with acute left ventricular failure can also raise systemic venous pressure in the absence of right ventricular infarction. Right ventricular infarction, therefore, should not be diagnosed simply by the presence of systemic venous congestion. PMID- 1743796 TI - Traumatic ventricular septal defect: serial follow-up with Doppler ultrasound. AB - A three-year-old girl presented with a gunshot wound of the chest. Cross sectional and Doppler echocardiography enabled precise location of the bullet, and assessment of the haemodynamic effects of the traumatic ventricular septal defect. Serial ultrasound examination in the acute stage confirmed that the bullet was well embedded in the left ventricular myocardium, and the ventricular septal defect was restrictive, enabling conservative management. PMID- 1743797 TI - Brucella endocarditis. AB - Between 1987 and 1990, three patients with abscesses produced by Brucella endocarditis were admitted to the Department of Infectious Diseases, "Ospedali Riuniti", Bergamo, Italy. In each case, the diagnosis was based on a history of ingestion of milk products, positive Wright serology, positive blood and valvar culture, and echocardiography. Medical therapy alone was not found to be effective in treatment, all patients requiring surgical intervention. One case required urgent surgical treatment and underwent three further operations up to the final implantation of a valved tube. According to our experience, Brucella endocarditis is a rare but serious disease which requires a combination of medical and surgical therapy. PMID- 1743798 TI - Transesophageal echocardiography and magnetic resonance imaging for the assessment of saccular aneurysm of the transverse thoracic aorta. AB - We report a patient who initially presented with hoarseness and was admitted to our hospital with chest pain, caused by a saccular aneurysm of the thoracic aortic arch. The initial diagnosis was made by cross-sectional echocardiography, the extension and morphology of the saccular aneurysm being detected by transesophageal echocardiography. Magnetic resonance imaging confirmed the measurements of the aneurysm and clearly showed the anatomic relation with surrounding structures and arch vessels. The patient refused operation and died during in-hospital stay. A rupture of the thoracic aneurysm was the cause of death. PMID- 1743799 TI - Endocarditis due to Streptococcus agalactiae presenting with myositis. AB - A case of endocarditis of the aortic valve due to Streptococcus agalactiae is described in which the patient presented with a myositis sparing the myocardium. The patient required emergency replacement of the valve, and made a good recovery. PMID- 1743800 TI - Amiodarone-induced torsades de pointes: the possible facilitatory role of digoxin. AB - Poorly controlled supraventricular arrhythmias in a hypokalaemic 74 year old woman were treated with oral amiodarone. This caused torsades de pointes, and was preceded by marked prolongation of the QT interval. The induction of torsades de pointes by amiodarone is thought to be an idiosyncratic reaction to amiodarone itself which is facilitated by electrolytic abnormalities. The present case, however, indicates the possibility of a pro-arrhythmic effect secondary to an interaction between amiodarone and digoxin. PMID- 1743801 TI - Percutaneous balloon mitral valvoplasty for young patients with rheumatic mitral stenosis. PMID- 1743802 TI - Striving for standards in bioequivalence assessment: a review. PMID- 1743803 TI - The challenge for clinical pharmacology in developing countries: the current situation. PMID- 1743804 TI - Effects of food intake on the bioavailability of sulpiride from AEA film-coated tablet having a pH-dependent dissolution characteristic in normal or drug-induced achlorhydric subjects. AB - The effect of food intake on the bioavailability of sulpiride from a commercial film-coated tablet (100 mg/T) treated with polyvinylacetal diethylaminoacetate (AEA), which remains undissolved at pH above 4 approximately 5, were investigated in four healthy male subjects in the normal state or in a drug-induced achlorhydric state. The drug was administered as a single oral 100 mg dose of sulpiride under the fasting and nonfasting state using a crossover study design. Fifteen urine samples were collected over a 48 h period following sulpiride administration to determine sulpiride concentrations by HPLC. The bioavailability was estimated from the cumulative amount excreted unchanged in urine over 48 h (Du48). When AEA film-coated tablet was taken by subjects in the normal state, the bioavailability under the fasting state differed markedly among the four subjects due to differences in gastric acidity. The effect of food intake on the bioavailability also differed markedly among the individuals, being lower in high gastric acidity subject and higher in those with low gastric acidity subjects. When AEA film-coated tablet was taken by subjects in a simulated achlorhydric state, the bioavailability under the fasting state was very poor for all four subjects and did not show inter-subject variation. With food intake, the bioavailability increased 6-fold, probably due to the more vigorous movement of the formulation in the gastrointestinal tract, since both the basal and the meal stimulated gastric acid secretion were markedly inhibited in the simulated achlorhydric state. PMID- 1743805 TI - Influence of type I and type II diabetes mellitus on phenytoin steady-state levels. AB - Phenytoin kinetics was studied in male type I and type II diabetic patients, ten in each group. Age and sex matched epileptic patients receiving phenytoin alone served as control groups. Steady-state concentration of phenytoin was significantly lower in both types of diabetics compared to respective controls. The Vmax and Vmax/Km of phenytoin were significantly increased in type I diabetics. The Vmax was unaltered in type II diabetics but the Vmax/Km was higher in them. Protein binding of the drug was decreased in both groups. It is concluded that phenytoin kinetics is increased in both types of diabetics which may be responsible for the lower steady-state concentration of the drug. PMID- 1743806 TI - Comparison of three regimens of Parlodel-SRO in levodopa-treated parkinsonians: a randomized double-blind crossover study. AB - Parlodel-SRO is a newly developed slow-release formulation of bromocriptine, which prevents initial plasma peak--a known source of adverse events--and extends the half-life of the compound, an interesting feature for the management of motor symptoms in Parkinsonians. This study was designed to determine the best daily administration schedule for 30 mg Parlodel-SRO in 18 parkinsonians previously treated with levodopa and standard Bromocriptine (Br). The 30 mg dose was replaced from one day to the next, in a randomized, double-blind latin square design trial. Three consecutive 7-day courses were implemented, during which a total daily dose of 30 mg P-SRO was administered in one dose, two intakes (b.i.d.) and three intakes, (t.i.d.) respectively. The b.i.d. schedule produced the best improvement in UPDRS scores, especially as to postural stability, walking, bradykinesia; it also provided greater pharmacological stability throughout the assessment day. Adverse event analysis was not in favor of a single daily dose. It appeared that P-SRO administered in two 15 mg intakes (morning and evening) produces the best benefit-risk ratio in Parkinsonians who were already being treated with levodopa. PMID- 1743807 TI - Hypocalcemic effects of rectal and intramuscular administration of synthetic salmon calcitonin. AB - To assess the acute biological activity of a new rectal form of synthetic salmon calcitonin (SMC), 10 healthy subjects were randomly assigned, according to a crossover design, to single doses of either 50 IU SMC intramuscularly or 100 IU SMC rectally. Ionized and total calcium were measured as SMC bioactivity indicators in blood samples collected during a 6-hour period after the administration of the drug. In all the subjects, rectal administration of 100 IU of SMC induced falls in both plasma total calcium and whole blood ionized calcium: similar levels were observed after intramuscular injection of 50 IU of SMC. The pharmacodynamic bioavailabilities for total and ionized calcium of the 100 IU suppository and the 50 IU intramuscularly were 106% and 60%. The total and ionized calcium AUCs were the same after i.m. injection and suppository. We conclude that, in normal subjects, synthetic salmon calcitonin administered by the rectal route at the dose of 100 IU is effective and has the same biological effects as 50 IU of SMC given intramuscularly. Therefore, this new rectal form may be a useful alternative to parenteral injection. PMID- 1743808 TI - Trimethadione tolerance test for one-point estimation of the severity of liver damage in cirrhotic patients. AB - We evaluated the adequacy of the trimethadione (TMO) tolerance test (the method of estimation from the serum dimethadione [DMO]/TMO ratio, DMO is only one metabolite of TMO, at 4 hours after oral administration of TMO) for estimating the severity of liver damage in 40 cirrhotic patients with and without hepatic encephalopathy. Serum dimethadione (DMO)/TMO ratios in a single blood sample after oral administration of TMO were significantly lower in cirrhotic patients with (0.07 +/- 0.02, p less than 0.05) or without (0.29 +/- 0.12, p less than 0.05) hepatic encephalopathy than in normal subjects (0.63 +/- 0.04). Serum DMO/TMO rations showed a good correlation with the following laboratory data: plasma indocyanine green retention at 15 minutes (r = -0.857, p less than 0.001), serum choline-esterase activity (r = 0.844, p less than 0.001), and albumin (r = 0.736, p less than 0.001). In cirrhotic patients with hepatic encephalopathy, the serum DMO/TMO ratio was found to be below 0.10, which was 16% of the normal level, by the TMO tolerance test. These findings suggest that the TMO tolerance test is a useful indicator of the hepatic parenchymal function in cirrhotic patients. PMID- 1743809 TI - Drugs and personality: comparison of drug users, nonusers, and other clinical groups on the 16PF. AB - This article reviews published 16PF research on drug users. It also compares the 16PF scores of a new sample of nonusers with scores of matched groups of heavy, chronic users of cocaine, amphetamine, opiates, and barbiturates/sedative hypnotics, as well as combined groups of stimulant users, depressant users, and a combined group of users of all substances. No significant differences were found among drug user groups, but the profile of the nonuser group was distinctive. K Means Cluster Analyses, as well as Cattell's Similarity and Pearson Product Moment Correlation Coefficients, were used to compare profiles of these new samples with the 19 groups described in an earlier meta-analysis of published 16PF studies. Data from the new samples did not cluster with data from other published research, although certain specific similarities appeared in more detailed correlational analyses. Methodological problems are discussed, and it is recommended that in future studies drug user groups be more carefully selected and defined, sample descriptions be more thorough and complete, complete profile information be routinely provided, and efforts be made to explore the utility of the Cattell CAQ in studies of drug users/misusers. PMID- 1743810 TI - Family involvement for improving the abstinence rate in the rehabilitation process of female alcoholics. AB - We investigated the effect of family involvement on abstention of 90 female alcoholics in recovery processes by multivariate analysis. The abstinence rate of the family-involved group was significantly higher than that of the group not involved (p less than .05). The logistic regression model in which family involvement, age, marital status, eligibility for welfare assistance, and history of previous psychiatric inpatient care were used as independent variables indicated that family involvement was the only variable having a significant effect on abstention (p less than .05). PMID- 1743811 TI - Memories of parental rearing in alcohol and drug addicts: a comparative study. AB - Memories of parental rearing were investigated in 48 polydrug addicts and 91 alcohol addicts with the EMBU, an instrument for assessing parental rearing styles. Drug addicts remember their fathers and mothers as more rejecting and overprotecting and their mothers as more favoring than do alcoholics. When the age and the sex of addicts are taken into account, the kind of addiction and the sex of the addicts can explain a part of the variance of the overprotection dimension by fathers and mothers. The age of the addicts can explain a part of the variance of the rejection dimension by fathers and mothers. Finally, the variance in the favoring dimension by mothers can be explained by the kind of addiction. PMID- 1743812 TI - Drug use among New York City prison inmates: a demographic study with temporal trends. AB - In a sample of over 2,500 medical charts from inmates arrested in 1986 in New York City, the rate of intravenous drug use peaked at 43% in male inmates aged 36 to 40. Younger inmates had progressively lower rates of intravenous drug use. Inmates detained for longer time periods and female inmates had particularly high rates of intravenous drug use. Rates of intravenous drug use were 30% among Hispanic, 26% among White, and 16% among Black inmates. Although overall rates of drug use among all male inmates in 1986 have remained unchanged since 1975, drug use was most prevalent in inmates aged 31 to 40 in 1986, the same criminal "cohort" which in 1975 had the highest rate of drug use. Implications for targeting of AIDS and drug-related counseling among inmates are discussed. PMID- 1743813 TI - Drinking habits among high school students in Perugia, Italy, in 1981 and 1988: time trends and correlates. AB - The prevalence of alcohol consumption among 9th (14-15 years old) and 13th grade (18-19 years old) high school students in Perugia, Italy, was investigated in 1981 and 1988. Wine was the most popular beverage, although its use declined in the 7-year period. Beer consumption remained stable, but it was at a lower level than wine. Overall, alcohol consumption showed a slight decline among both 9th and 13th graders. However, the proportion of excessive drinkers increased, and a growing phenomenon of drunkenness among students was observed. Alcohol consumption was positively associated with sex and smoking and negatively associated with father's education and knowledge of the health hazards of alcohol abuse by multivariate analysis. PMID- 1743814 TI - Alcohol use and negative consequences among American college students in West Germany. AB - Numerous investigations have recently focused on the prevalence and causes of problem drinking among American college students. The present study examined alcohol consumption and negative consequences due to drinking among 216 American college students at an American university in West Germany. American students in Germany reported a substantially higher frequency and amount of drinking, along with higher rates of negative consequences as compared to their stateside peers. The data are discussed in terms of the relationship between the American collegiate life-style of alcohol abuse and life in an alcohol-permissive society. Recommendations for changing the collegiate norm of alcohol abuse are presented. PMID- 1743815 TI - The role of the psychologist on the drug user treatment team. AB - Current practice in drug user treatment tends to provide, within any one agency, essentially the same treatment for all clients entering that agency. Instead, an agency should use a team approach, with a specific and unique treatment plan for every client, provided by the members of the team. The psychologist should play a central role on this team, being responsible for the treatment plan, for an individual evaluation plan, for assessing progress, for program evaluation, and, in many instances, for supervision of treatment staff. The functions and the different roles played by the psychologist are described, and the characteristics and skills needed for success are listed. PMID- 1743816 TI - Adult children of alcoholics: the effects of background and treatment on ACOA symptoms. AB - This research attempts to identify the factors that differentiate adult children of alcoholics (ACOAs). A national purposive sample of ACOAs (n = 500) was administered an ACOA index measuring ACOA symptoms. An ANOVA analysis for the ACOA index scores showed gender, minority race or ethnicity, rating of parents' relationship, receiving help as a child, and seeking treatment as an adult to have significant effects. Notably, minorities scored significantly lower on the ACOA index, and seeking treatment increased the scores, even in interaction with parents' relationship and receiving help as a child. These findings point to the need for differentiating treatment for ACOAs and developing more effective treatment in general. They also confirm the importance of offering even informal support to children in troubled families. PMID- 1743817 TI - The alcohol use disorders identification test (AUDIT) in a college sample. AB - This study was conducted to estimate the psychometric properties of the questionnaire section of the Alcohol Use Disorders Identification Test (AUDIT) in a college sample using DSM-III criteria for alcohol abuse as the criterion standard. This alcohol screening test was developed for the 10 country AMETHYST project. In this young adult sample the instrument exhibited a sensitivity of .84 and specificity of .71 when utilizing the recommended cut-off score of 11. The 10 item questionnaire section of the AUDIT appears to have important advantages over other alcohol screening instruments such as the CAGE and the MAST. PMID- 1743818 TI - Recidivism among high risk youths: a 2 1/2-year follow-up of a cohort of juvenile detainees. AB - We report some results from a longitudinal study of juvenile detainees. Analyses were directed toward determining whether the youths' alcohol or other drug use and their emotional/psychological problems at entry into the detention center predicted subsequent arrests for new offenses during the 24 and 30 months following their initial interviews. Statistically significant relationships were found between the youths' demographic characteristics (age, race, gender), referral history, reason for placement in the detention center, cocaine use (as measured by urinalysis), and recidivism. The magnitude of these relationships increased with the length of the follow-up period. PMID- 1743819 TI - The effect of nicotine, silver acetate, and placebo chewing gum on the cessation of smoking. The influence of smoking type and nicotine dependence. AB - The effects of nicotine (NI), silver acetate (SA), and ordinary (PL) chewing gum on the cessation of smoking were compared through ratings on six smoking types and physiological nicotine dependence (F-score) in a placebo-controlled and randomized study that included 496 smokers in a group-support setting. Results were evaluated after 26 weeks. Ratings on smoking types 1, 3, 4, 5, and 6 and F score were related to success rates. The effect of NI was superior to SA in smokers with high type 1 ratings, the effects of NI and SA were almost equal and superior to PL in smokers with high type 4 and 6 ratings, and the effect was independent of the F-score. Treatment of smokers with NI and SA should be restricted to smoking types in which an effect superior to PL is documented, and research should be performed to find support for smoking types where SA and NI have a clear effect. PMID- 1743820 TI - Substance misuse among native and rural high school students in Quebec. AB - A questionnaire exploring the smoking habits, past and current use of alcoholic beverages, cannabis, and other illicit drugs was distributed among Francophone and Native high school students in a rural area of Quebec. The lifetime prevalence figures indicated that use of illicit drugs was significantly higher among Native students. This held true particularly for stimulants and inhalants (p less than .001). Figures for the 1-year prevalence indicated that use of stimulants in Native students remained still significantly higher (p less than .01). However, consumption of alcoholic beverages was more important in Francophone students (p less than .05). A gender difference was observed in Native students, females reporting an earlier involvement with most substances under study. This tendency decreased with age. The implications of this study for the prevention of alcohol and substance abuse among rural and Native youths are discussed. PMID- 1743821 TI - Alcohol control: issues in taxing, production, and distribution. AB - Many developing nations are experiencing increasing problems associated with their people's increasing use of the drug alcohol. Economic interests and the governments' need for revenue are predominant and obscure the need for the governments to accept their public health responsibilities. As indicated in this paper, the control of alcohol problems requires developing nations' governments to take a balanced approach to taxing, production, and distribution of alcoholic beverages. Furthermore, the UN and the developed nations must participate in these endeavors to ensure that the developing nations will not be exploited commercially. PMID- 1743822 TI - Crack: new directions in drug research. Part 2. Factors determining the current functioning of the crack economy--a program for ethnographic research. AB - Factors which hypothetically influence rates, volumes, and methods of income generation in crack distribution, use, and misuse are indicated, and a research program to investigate them is suggested. This research will contribute significantly to the development of a theoretical framework which adequately relates substance using/abusing and trafficking populations to the wider community and will explain why crack use and distribution have had such different outcomes than marijuana. Factors to be researched include: polyethnicity, crack related deculturation, gender differentiation in crack use and effects, neighborhood effects, vertically organized crack-distributing organizations, crack-related violence and crime, and replacement of previous drug markets by crack. PMID- 1743823 TI - Correcting for the underreporting of drug use in opinion surveys. AB - Survey data is one of the major mechanisms for measuring patterns of drug use across populations. But because drug use can be both a legal and an illegal activity, the accuracy of self-reported measures of use has been a continual problem. The sealed booklet questionnaire overcomes these problems by guaranteeing the respondent some degree of anonymity. This paper reports results from a modified booklet method used in a drug use survey with a national population sample. The method produces better estimated than direct questions, yet guarantees the respondent anonymity. In addition, the analysis shows that underreporting for different drugs is behaviorally motivated rather than drug specific. The results suggest that adults are more concerned about potential use, while adolescents are more concerned about past use. PMID- 1743824 TI - The balanced placebo design: effects of alcohol and beverage instructions cannot be independently assessed. AB - Subjects were randomly assigned to the four cells of the balanced placebo design, with 10 males and 10 females per cell. Following told-alcohol or told-no alcohol beverage instruction manipulations, participants consumed either a vodka-tonic beverage containing a dose of vodka sufficient to induce a peak blood alcohol level of 0.05% or a beverage containing only tonic water. Subjects' self-report ratings of beverage alcohol content indicated that alcohol overrode the effects of beverage instructions in the told-tonic/given-alcohol condition. It was concluded that the design cannot independently evaluate effects of both alcohol and beverage instructions when behaviorally significant alcohol doses are administered. PMID- 1743825 TI - A comparison of perceived self among drug addicts and nonaddicts. AB - The Adjective Check List was employed to compare the self-concepts of 41 male drug addicts, 44 male nonaddicted technical school students, and 37 male nonaddicted psychiatric patients. A large number of significant differences were found. Three scoring systems were used that yielded a total of 23 scales. There were nine scales on which the addict group was different from the normal group but the psychiatric nonaddict group was not. These nine scales are of particular interest since they represented traits that differentiated addicts from normals. These traits appear to be related to addiction rather than general maladjustment. Implications for treatment are discussed. PMID- 1743826 TI - The impact of drug testing on the morale and well-being of mandatory participants. AB - The impact of drug testing on the morale of mandatory participants was assessed through interviews and questionnaire responses of 500 intercollegiate athletes required to participate in a urine testing program. Subjects varied widely in their experiences. Most were not greatly affected, but some were embarrassed, humiliated, upset, and anxious about being inaccurately identified as drug users. Others experienced positive benefits: new information, a novel and interesting conversation piece, and a socially acceptable way to refuse drugs offered in friendship. Some said that testing benefited their athletic performance and school work. A number of recommendations were made to humanize and improve the experience: a better orientation about what to expect, more effective educational sessions, a warmer, more comfortable testing setting, more reasonable drug testing objectives, and more rigorous testing standards. PMID- 1743827 TI - Behavioral strategies used by long-term successful self-quitters. AB - Smoking-cessation programs have been shown to produce unreliable long-term results. Thus, efficient methods still need to be identified. One way of getting relevant information on successful smoking cessation is to study the quitting methods of unaided, long-term, successful quitters. A structured questionnaire was designed specifically for this purpose. Results from 70 self-quitters indicated that self-quitters typically had high motivation before attempting to quit and used aversive and operant methods currently stressed in the literature. Graded habituation and nicotine-based methods were used by some self-quitters. The findings suggest a two-stage model of quit-smoking program which gives greater attention initially to the systematic development of motivation to quit. This model, it is postulated, might enhance the long-term efficacy of smoking cessation programs. PMID- 1743828 TI - High energy shock waves in the treatment of delayed and nonunion of fractures. AB - The treatment of delayed and nonunion of fractures by a single extracorporeal dose of high energy shock waves generated in a water medium and focused on the fracture site is reported. The shock waves break up sclerotic bone by producing microfissures and numerous bony fragments because of the difference in impedance between bone (and calculi) and soft tissues. Osteogenesis is stimulated and contributed to union in 70 out of 82 fractures within a reasonable time. Treatment was given as an outpatient with regional anaesthesia; there were no side effects or complications. PMID- 1743829 TI - Results of the Putti-Platt operation for recurrent anterior dislocation of the shoulder. AB - Between 1973 and 1981, 101 patients had a Putti-Platt repair for recurrent dislocation of the shoulder; 89 of them were followed up and 43 underwent a clinical examination, 23 being assessed with the Cybex dynamometer. The 46 who did not attend were interviewed by telephone. The mean follow up time was 8 +/- 2 years (range 5-14 years). Redislocation occurred in 18 patients (20%), but this was twice as high in patients who were aged under 26 years at the time of operation compared with those who were older (29% versus 13%). The time of recurrence was between 1 and 11 years after operation. A decrease in strength and power of abduction, internal and external rotation, was found in the affected shoulder. Restriction of all measured movements, particularly external rotation, was also found in all patients. Nevertheless most had a high functional score and relatively few symptoms. We conclude that the Putti-Platt procedure has a high recurrence rate in younger patients, and we hesitate to recommend it for young active individuals. PMID- 1743830 TI - Delayed open reduction for supracondylar fractures of the humerus. AB - Twenty children with grade IV supracondylar fractures of the humerus had an open reduction 11 to 17 days after injury. The delay was due to swelling and blisters. Most patients recovered a useful range of movement and there were no complications. A posterior approach with V-Y plasty of the triceps makes it easy to align the fragments and reduces the incidence of cubitus varus. Apprehension about the risk of increasing the extent of myositis ossificans is unfounded. PMID- 1743831 TI - Management of the Galeazzi fracture. AB - Fifty-one adults with Galeazzi fractures were treated by operation and the results compared in cases treated early, late and after inadequate initial treatment. We conclude that in cases treated up to 10 weeks after injury, immobilisation with the forearm in full supination in an above elbow cast helps to maintain stability of the inferior radioulnar joint. The distal end of the ulna should only be excised after 6 months, and if the symptoms warrant it. In patients who were inadequately treated initially, the distal end of the ulna should be excised at the time of the operation on the radius, but a poor result is the inevitable outcome. Union, or nonunion of the ulnar styloid did not affect the end result. PMID- 1743832 TI - Stress fracture of the diaphysis of the ulna. AB - Stress fracture of the diaphysis of the ulna is rare and only 6 cases were found in a literature review. We present a further case occurring in a weightlifter. PMID- 1743833 TI - Vascularised osteocutaneous fibular transfer to the tibia. AB - We have reviewed 25 cases of vascularised osteocutaneous fibular transfers carried out between 1982 and 1988. The patients all had chronic osteomyelitis of the tibia, with extensive bone loss and associated soft tissue defects, following severely comminuted fractures. Union of the grafted bone could be seen in radiographs taken 3 to 4 months after operation. The results were generally satisfactory, but there were some complications. PMID- 1743834 TI - Complications of suppurative arthritis and osteomyelitis in children. AB - Three children with suppurative arthritis and osteomyelitis are described to emphasise that delayed or incorrect diagnosis may lead to serious cardiopulmonary complications. In two patients, bilateral bronchopneumonia developed with pneumatocoeles, pneumothorax and empyema. The other had cardiac failure from septic pericarditis. In one case, disarticulation of the knee was needed as a life-saving measure, and the other leg developed an infected pseudarthrosis of the tibia. The causative organism in each case was staphylococcus aureus and no evidence of immunodeficiency was demonstrated. PMID- 1743835 TI - Radiological study of alignment after total knee replacement. Short radiographs or long radiographs? AB - The axial alignment on short and long radiographs was measured in 50 knees in 34 patients who had undergone posteriorly stabilised (Insall-Burstein) condylar knee arthroplasty. A mean difference of 1.6 degrees was found when the tibiofemoral angles were compared on short and long radiographs. Short radiographs are probably adequate for routine assessment of knee replacements in a busy out patient clinic, but for accurate scientific studies the long radiographs are preferable. PMID- 1743836 TI - Posteriorly stabilised (Insall-Burstein) total condylar knee arthroplasty. A follow-up study of 157 knees. AB - We reviewed 157 knees in 118 patients who underwent posteriorly stabilised (Insall-Burstein) knee replacement arthroplasty. Their mean age at operation was 69 years (range 47 to 85 years) and the average follow-up was 3.5 years (range 2 to 7 years). The "BASK" knee function assessment chart was utilised to evaluate the functional and clinical results. One hundred and thirty-five knees (86%) had excellent or good results, 16 knees (10%) had fair results and six (4%) had poor results. The mean postoperative BASK score was 79 points and the average postoperative knee flexion was 95 degrees (range 65 degrees to 130 degrees). Two patients had a superficial infection, one deep sepsis requiring revision arthroplasty and two mechanical loosening. Patellar impingement symptoms were present in 8% of the knees, although they were troublesome in less than half. Varus alignment of the knee and a varus tilt of the tibial component of more than 2 degrees correlated with the incidence of radiolucent lines around the tibial prosthesis. 90% of the patients were pleased or satisfied with the functional result. The total condylar knee is a safe, reliable and versatile prosthesis. PMID- 1743837 TI - Fibular aplasia. Early surgical correction in two cases. AB - Two infants with bilateral fibular aplasia are described. They were operated on at 1 1/2 years and 8 months respectively in order to obtain a stable axial position of the foot beneath the tibia. The procedures consisted of soft tissue releases together with angulation osteotomies of the tibiae in one, and splitting the distal tibial epiphysis in the other. Both patients are now able to walk well barefoot or in custom-made shoes; no orthotic devices are needed. This type of conservative approach should be considered rather than amputation in selected cases. PMID- 1743838 TI - Autogenous osteoperiosteal grafts in the reconstruction of full-thickness joint surface defects. AB - Free, autogenous periosteal grafts from the medial metaphysis of the proximal tibia have been used to reconstruct full thickness cartilage defects of the articular surfaces of the knee joint. If there was a bone defect, it was initially filled with cancellous bone graft. The method is illustrated by six patients, three with acute traumatic patellar defects and three with local sclerotic osteochondritis of the medial femoral condyle. The latter had loose fragments unsuitable for fixation and single excision would have left a large and deep defect. The grafts have given satisfactory results, 14 to 59 months after the procedures. Clinical grading of the defects has been monitored by radiographs with arthroscopy of two knees and CT scan of one knee. PMID- 1743839 TI - [Total prosthesis after ankylosis of the hip joint. Report of 22 cases]. AB - Between 1968 and 1987 we carried out a total replacement arthroplasty on 22 hips which were either ankylosed or had previously undergone arthrodesis. The hips were revised because of pain due to pseudoarthrosis or malposition, pain in the other joints such as the lumbar spine, the ipsilateral knee or the contralateral hip, fractures about the hip, or professional disability. Significant functional and subjective improvement was obtained. The revised hips were painfree, stable and had an average range of flexion of 70 degrees. Pain in other joints was improved if their degenerative changes were moderate, but many required further procedures. Revision of a hip arthrodesis to a replacement arthroplasty is a worthwhile procedure in suitable cases. PMID- 1743840 TI - Rupture of the ankle ligaments. AB - A prospective randomised trial of treatment of ruptured ankle ligaments was carried out at our institute. Two hundred patients were randomly assigned to 4 treatment groups. The results at 1 and 2 years after injury showed that functional treatment with a newly designed brace appeared to be the method of choice. This gives good mechanical stability, a shorter time off work and the ability to resume full sporting activity within 3 months of injury. Operation is only indicated for dislocations of the ankle and foot, ankle ligament rupture with additional intraarticular damage and second stage injuries or re-ruptures. PMID- 1743841 TI - Immune inhibition of repair of canine skull trephine defects implanted with partially purified bovine morphogenetic protein. AB - The healing of 14-mm trephine skull defects was observed in ten adult mongrel dogs. First and second set trephine operations were performed to determine whether xenogeneic bovine bone morphogenetic protein (bBMP) and associated bone matrix water-insoluble noncollagenous proteins (iNCP) incite an immunological humoral response inhibiting bone repair. The effects of immunization to BMP/iNCP were observed by serum radioimmunoassay, and by correlated roentgenographic and histological analysis of deposits of new bone. The first set implants of bBMP/iNCP induced 96% healing while the regeneration of the second set trephines was 34% less than the first set. The second set was associated with a significant increase in serum anti-BMP antibodies. While xenogeneic bBMP induced complete healing of trephine defects when implanted without previous immunization, and repair in response to a second set of bBMP/iNCP was always incomplete, further research with high purified recombinant BMP is required to measure immune effects in a statistically significant number of pure bred recipients. PMID- 1743843 TI - Comparison of distraction epiphyseolysis and partial metaphyseal corticotomy in leg lengthening. PMID- 1743842 TI - The treatment of spinal kyphosis. AB - The modern management of kyphosis depends on the diagnosis, but there are common factors on which rational treatment can be based. An understanding of the biomechanics is very important, especially in planning operations on the spine. The greatest single advance has been the anterior approach. Scheuermann's disease in children is best treated by bracing, but most other deformities need anterior and posterior fusion. Modern instrumentation benefits both the patient and the surgeon. PMID- 1743844 TI - The John Frederick Adrian Sprent Prize of the Australian Society for Parasitology. Citation for Desmond R. Hennessy. PMID- 1743845 TI - The John Frederick Adrain Sprent Prize of the Australian Society for Parasitology. Citation for Stephen C. Barker. PMID- 1743846 TI - Manipulation of benzimidazole pharmacokinetics (J. F. A. Sprent Prize lecture, September 1987). PMID- 1743847 TI - Evolution of host-parasite associations among species of lice and rock-wallabies: coevolution? (J. F. A. Sprent Prize lecture, August 1990). PMID- 1743848 TI - Experimental American leishmaniasis and Chagas' disease in the Brazilian squirrel monkey: effect of dual infection on antibodies to parasite antigens. AB - Adult, laboratory-bred squirrel monkeys (Saimiri sciureus) were infected with either Leishmania braziliensis braziliensis or L. b. panamensis and, 42 weeks later, they were challenge-infected with Trypanosoma cruzi. Another group of monkeys was infected with T. cruzi and challenged with L. b. braziliensis after 42 weeks. Immunoblotting was used to examine parasite antigens bound by antibodies in plasma obtained from the monkeys during the course of primary and challenge infections. During primary infections Leishmania-infected monkeys produced antibodies which bound to a number of Leishmania antigens, most notably a Leishmania antigen of 72 kDa, which were not recognized by antibodies produced by the monkeys given a primary infection of T. cruzi. These Leishmania-induced antibodies were no longer detectable 42 weeks after primary infections. However, when the Leishmania-infected monkeys were challenged with T. cruzi they once again produced antibodies capable of binding numerous Leishmania antigens, including the antigen of 72 kDa, which had not been recognized by antibodies produced by the monkeys with primary T. cruzi infections. A similar phenomenon was observed in T. cruzi-infected animals following Leishmania challenge. PMID- 1743849 TI - Mechanism of 3-0-methylglucose uptake by Hymenolepis diminuta. AB - The mechanism by which Hymenolepis diminuta (Cestoda) absorbs 3-0-methylglucose (30MG) in vitro was analyzed. Influxes of 0.1 and 0.01 mM-3H-30MG during incubations ranging from 5 s to 60 min were not affected significantly when 10 mM unlabeled 30MG was present as an inhibitor. After 60 min in 0.1 mM-3H-30MG, the concentration of labeled substrate within tapeworms (0.04 mumol ml-1 worm water = 0.04 mM) was less than that of the bathing medium. Tapeworms incubated for 1 h with either 5 mM-glucose or 5 mM-beta-methylglucose (beta MG) gained 15-20% more water than did tapeworms in saline alone, but addition of 5 mM-30MG to the saline had no significant effect on weight change. When the 3H-30MG concentration was varied from 0.01 to 10 mM, influxes were a linear function of substrate concentrations. These analyses show that H. diminuta absorbs 30MG by simple diffusion alone. Thus, use of this monosaccharide to estimate the internal concentration of actively transported sugars (e.g. glucose or beta MG) in H. diminuta is invalid. PMID- 1743850 TI - Echinococcus granulosus: development of an intermediate host mouse model for use in vaccination studies. AB - A mouse model has been developed to evaluate potential protective antigens which could render intermediate hosts resistant to a challenge infection with Echinococcus granulosus eggs. DBA/2J, CBA/J, Balb/cJ, C57/B16J and CF-1 mice were initially infected orally and parenterally with eggs, hatched eggs or activated oncospheres. Generally less than 1% of the oral dose established as cysts. Mean cysts counts were increased when Balb/cJ mice were injected intraperitoneally or intravenously with activated oncospheres. A challenge regime using 600 activated oncospheres injected intraperitoneally into adult Balb/cJ mice was subsequently adopted yielding means of 15-51 cysts per mouse. When activated oncospheres were injected intraperitoneally into Balb/cJ, DBA/2J and CF-1 mice, cysts were restricted to the peritoneal cavity. Activated oncospheres injected intravenously, however, lodged almost exclusively in the lung and thoracic cavity, except in DBA/2J mice where 55% lodged in the liver. This anatomical localization enabled the outcome of prior infection and challenge to be monitored separately. Prior infection rendered Balb/cJ mice fully resistant to subsequent challenge. PMID- 1743851 TI - Genetic variation in the Heterodoxus octoseriatus group (Phthiraptera): a test of Price's model of parasite evolution. AB - Most of the genetic variation in the H. octoseriatus group is present as fixed gene differences between species which have been described on morphological criteria. Based on allozymes, the taxonomic status of some species was challenged. There was insufficient evidence, however, to demonstrate that these were not 'good' biological species. Overall, the limited intraspecific variation was present as fixed gene differences among lice from different hosts and from different colonies of hosts; heterozygotes were rare. Two predictions derived from Price's model of parasite evolution were met: populations of lice were genetically homogeneous and, where genetic markers were present, we found substantial genetic variation among populations. These data contrast with those for endoparasitic helminths, where, in general, the amount of genetic variation is similar to that of free-living invertebrates. PMID- 1743852 TI - Dactylogyrids on the gills of roach in central Finland: features of infection and species composition. AB - Monogenean parasites were examined from the gills of 660 roach (Rutilus rutilus) in four interconnected lakes in Central Finland between February and November 1986 and in three of the same lakes between February and December 1988. One of the lakes is eutrophic and polluted due to a paper and pulp mill, one is oligotrophic and in a natural state, and the other two lakes are eutrophic. The prevalence of Dactylogyrus infection was always high. Differences between the lakes and the years were observed in the intensity of infection, which was significantly higher in the polluted lake. The intensity was also higher in older fish. Nine Dactylogyrus species were found, and of these D. crucifer and D. nanus were numerically dominant in all of the lakes studied, especially in the oligotrophic lake. In 1986 D. fallax, D. similis and D. suecicus constituted significant proportions of the fauna in the polluted lake. D. micracanthus was most common in the eutrophic lakes. In 1988 the species composition in the polluted lake was most similar to that in the eutrophic lake. PMID- 1743853 TI - Trypanosoma brucei: peptide mapping of partially homologous variable surface glycoproteins. AB - Antigenic variation in Trypanosoma brucei is caused by amino acid sequence changes in a major surface glycoprotein. Each trypanosome may contain between 100 and 1000 genes coding for this glycoprotein. Some of these genes are members of partially homologous gene families. In addition, segments of different genes may combine to form 'hybrid' or 'mosaic' genes. Thus, surface glycoproteins exist containing varying amounts of amino acid sequence homology. For investigations of molecular mechanisms of antigenic diversity it is important to identify sub-sets of trypanosomes expressing related surface glycoproteins. We describe here a simple method based on trypanosome surface labeling followed by peptide mapping to indicate homologous peptides present in one sub-set of T. brucei surface glycoproteins. PMID- 1743854 TI - A cladistic analysis of the genera in the subfamily Pudicinae (Nematoda, Trichostrongyloidea, Heligmonellidae). AB - A parsimony analysis was performed on 37 specific taxa belonging to the subfamily Pudicinae (family Heligmonellidae), which contains parasites mainly from South American caviomorph rodents. Thirteen characters were used from the synlophe (rotation of axis, presence of carene, carene asymmetry, presence of comaretes, single ventral comarete length, ridge discontinuity, ventral ridge numbers, presence of a peculiar posterior synlophe, presence of supernumerary spines) and the male caudal bursa (relative length of rays 9 and 10, caudal bursa type, division of the dorsal ray, divergence of the 10th rays). The cladogram shows a consistency index of 1.0. The subfamily Pudicinae has two synapomorphies. Two suprageneric groups are recognized. Suprageneric group 1 shows one synapomorphy and contains Heligmostrongylus, Fuellebornema, Sciurodendrium and Pseudoheligmosomum; suprageneric group 2 shows two synapomorphies and contains Pudica, Acanthostrongylus, Justinema and Durettestrongylus. Five genera are defined on the basis of synapomorphies. The genera Heligmostrongylus, Sciurodendrium and Pudica which are considered paraphyletic, however, are retained due to lack of knowledge as to their relationships. PMID- 1743855 TI - A nuclear magnetic resonance study of the glucose metabolism of Hymenolepis diminuta exposed to histamine and serotonin in vitro. AB - The direct effects of the inflammatory mediators, histamine (HI) and serotonin (SE), on the glucose metabolism of Hymenolepis diminuta in vitro were studied by analyzing the excretory products from culture media, containing D-1-13C-glucose and various concentrations of HI and/or SE, by 1H-nuclear magnetic resonance (n.m.r.) spectroscopy. The results revealed that HI markedly accelerated the glycolysis process by increasing the amount of lactate production. The increased glycolytic activity was reflected in a concentration-dependent increase in glucose uptake. Excretion of acetate was also stimulated by HI. A low concentration of SE significantly increased succinate, acetate and lactate excretions, whereas a high concentration had little effect on lactate production and significantly decreased succinate and acetate excretions. A combination of HI and SE treatment at a low concentration had no significant effect, but at a high concentration showed an additive effect, with an increase in lactate production, a decrease in succinate production and an increase in glucose uptake. Thus this work confirms that HI and SE directly influence, albeit differently, energy metabolism of the tapeworm H. diminuta. PMID- 1743856 TI - Aspects of the morphology and life cycle of Lecithocladium excisum (Digenea, Hemiuridae), a parasite of Scomber spp. AB - Previously undescribed motile cystophorous cercariae which develop in sporocyst like germinal sacs in the bullomorph opisthobranch Philine aperta are experimentally shown to develop into Lecithocladium excisum (Digenea, Hemiuridae), a common stomach parasite of mackerel Scomber scombrus in the north east Atlantic and adjacent seas. Between 3 and 8% of P. aperta from the northern Oresund, Denmark, were infected with cercariae of L. excisum. Ninety per cent were infected with Rhopalura sp. (Orthonectida). Copepods of the genera Acartia, Paracalanus, Pseudocalanus, Eurytemora and Oithona were experimentally infected. Pressure exerted by their mouth limbs caused delivery tube eversion and the injection of the cercarial body into the copepod haemocoel. The metacercariae did not grow in the above mentioned hosts at 12 degrees C, but 590 microns long metacercariae developed within 22 days in laboratory-reared A. tonsa at 18 degrees C. The ctenophore Pleurobrachia pileus and the holoplanktonic polychaete Tomopteris helgolandica, which were found to be naturally infected with metacercariae of L. excisum, may act as transport hosts. PMID- 1743857 TI - Taenia solium: inhibition of spontaneous evagination of cysticerci by the host inflammatory capsule. AB - The effect of the host's inflammatory capsule or of physical restraint on the spontaneous evagination capacity of Taenia solium cysticerci was evaluated. Parasites obtained from infected pig muscle, in which the surrounding inflammatory capsule was not eliminated, were unable to evaginate spontaneously after 12 or 60 h of culture. This phenomenon was not abolished when the capsule was eliminated and the parasites were cultured in semi-solid agar or in liquid medium. PMID- 1743858 TI - A simple method for the purification of mitochondrial DNA from Plasmodium falciparum. AB - Mitochondrial DNA (mtDNA) from Plasmodium falciparum was isolated by conventional differential centrifugation in an SS34 rotor, a simpler method than CsC1 centrifugation of total DNA as employed by other workers. The nature of the sample was verified by sequencing a polymerase chain reaction (PCR) product obtained using oligonucleotide primers derived from known malarial mtDNA sequence. PMID- 1743859 TI - Babesia bovis host cell recognition proteins. AB - Babesia bovis enters host erythrocytes by invagination but nothing is known of the proteins involved. By means of metabolic labelling, differential centrifugation in oil and salt elution, a number of babesial proteins have been shown to bind to bovine erythrocytes. Strong binding is evidenced only by a 38/19 kDa pair. Preliminary experiments indicate that these two proteins also bind to human erythrocytes, although apparently to a lesser extent. PMID- 1743860 TI - A cyst-like stage of Blastocystis hominis. AB - A cyst-like form of Blastocystis hominis is described in stools and in culture. This form is more common in stored stools than fresh material. A cyst wall is secreted under the surface coat of the cell, and the surface coat and cell debris subsequently separate from the cyst. Whether this stage can withstand adverse environmental conditions and is infective to a new host remain to be determined. PMID- 1743861 TI - Ocular leprosy--the continuing challenge. PMID- 1743862 TI - Comparison of the old and new W.H.O. leprosy disability grading scheme for ocular disabilities. AB - We compared the old (1970) and new (1988) World Health Organization schemes for classifying the ocular disabilities in leprosy patients. 509 leprosy patients from eight resettlement villages in central South Korea were examined and graded by eye according to both of the schemes. A more liberal definition of severely disabled in 1988 resulted in a 119% increase in eyes graded as severely disabled in this population. 59 eyes were graded as severely disabled by the old scheme and 129 eyes were so graded according to the new scheme. Keratitis, one of three measures of moderate disability in the old scheme, was replaced by corneal anaesthesia in the new scheme, but this change did not make a substantial difference in the number of patients in the moderately impaired category. In the absence of longitudinal studies documenting the significance of keratitis, it is unclear whether the change in an improvement. The new disability scheme improved upon the old by removing the criteria for mild impairment. PMID- 1743863 TI - Leukoplakia of the cornea presenting as fingerprint epithelial lines: a case report. AB - Opacities in association with fingerprint patterns of the epithelium were seen in the upper half of the right cornea of a 52-year-old patient complaining of decreased vision. Removal of the corneal epithelium from the involved area resulted in visual improvement and normalization of corneal appearance. Histological examination of the removed epithelium failed to reveal the typical intraepithelial formation of basement membrane invaginations even in the areas corresponding to the fingerprint patterns. Moderate to severe degree of atypia were seen in the epithelial cells. No abnormalities were observed in 3 conjunctival specimens excised at the time of epithelial removal. The diagnosis of corneal dysplasia (leukoplakia) was made. Our report is the first description of epithelial fingerprint patterns of the cornea associated with leukoplakia. PMID- 1743864 TI - In vitro viability of choroidal melanomata following pre-enucleation irradiation. AB - In a group of eighteen patients with uveal melanomas, seven underwent low-dose pre-enucleation irradiation of approximately 2000 cGy. All the tumours were propagated in tissue culture and the growth characteristics of tumour cells from irradiated eyes were compared with tumour cells from non-irradiated eyes. Cultures were observed with phase-contrast microscopy, and radioactive thymidine labelling was used to study cell turnover. Although tissue samples from peripheral areas of irradiated tumours produced a mixture of viable and non viable cells, with reduced ability to attach to substrate, central regions of irradiated tumours contained viable cells which propagated freely in tissue culture. PMID- 1743865 TI - Reservations about the Malbran technique. PMID- 1743866 TI - Corneal endothelial cell morphology under permanent wear of rigid contact lenses. AB - The influence of the permanent wear of rigid high Dk-lenses (nominal Dk 71 or 92) with elliptical geometry on the corneal endothelium was assessed. For this purpose the endothelium of 16 patients was compared by specular microscopy before and after the permanent wear. The wearing time of the lenses varied between 7 and 24 months. Computerized morphometric analysis of the photographs revealed that the variability in cell size (polymegathism) and in cell shape (pleomorphism) did not change during the wearing period. It is suggested that this is due to the high gas-permeability and the elliptical geometry of the contact lenses. PMID- 1743867 TI - Spectrophotometric analysis of sodium fluorescein aqueous solutions. Determination of molar absorption coefficient. AB - The usefulness of sodium fluorescein (SF) and related physical parameters were analysed. Two factors that may affect the molar absorption coefficient (epsilon) of this compound were the presence of impurities and the pH of the solution. As discrepant values can be found in the literature for that coefficient, a purification technique was used and SF quantification was performed according to sodium concentration determined by atomic absorption spectrophotometry. The molar absorption coefficient of the SF solution in phosphate buffer pH 7.4 was determined. To study the influence of pH on epsilon determination, absorption spectra at pH1, 3, 5, and 10 were also analysed. PMID- 1743868 TI - B-mode echography of choroidal melanoma; echographic and histological aspects of choroidal excavation. AB - The B-mode images of 32 patients affected with a malignant melanoma of the choroid were studied, in particular with respect to choroidal excavation. The degree of visibility of choroidal excavation at the B-scan was compared with the thickness of the choroid, scleral invasion, vascularisation, retinal detachment and the reflectivity of the tumour. None of these histological and echographical features appeared to be significantly related to the degree of the visibility of choroidal excavation. Also the condition of the choroid was studied. At examination of all the histological sections no choroid was found between tumour and sclera. This implies that choroidal excavation should be visible at echograms in every case instead of only in 75% of the cases as was found for our series. PMID- 1743869 TI - Congenital ichthyosis in a Libyan child with ophthalmic manifestations. AB - This report presents a Libyan child with congenital ichthyosis of the recessive lamellar variety complicated by severe ectropion of both upper and lower eyelids. Over a period of 12 months the degree of ectropion diminished and the anterior segments of the eyes were preserved using regular lubricating drops, vitamin A ointment and intermittent topical antibiotic therapy. Despite the pronounced initial upper eyelid ectropion no surgery was required to relieve the ectropion or prevent corneal exposure. PMID- 1743870 TI - A comparison of unweighted and fluctuation-weighted indices (within the central 28 degrees of glaucomatous visual fields measured with the Octopus automated perimeter). AB - The main visual field indices of Flammer and the analogous ones of Heijl have been compared based on a population of 113 glaucomatous visual fields. It is shown that for the population studied, the differences between the two sets of indices are negligible for Octopus G1 program results and that they may thus be used interchangeably. PMID- 1743871 TI - Cataract instruments and devices--'cost and quality'. PMID- 1743872 TI - Nasal mucociliary function in the normal newborn. AB - Nasal mucociliary transport has been studied using the seroalbumin-Tc99m radioisotope method in 10 adults and 10 normal newborns under 28 days of age. The mean transport velocity was 8 and 6 mm/min for the normal adults and newborns, respectively, with no significant differences between the two (P = 0.07). PMID- 1743873 TI - The influence of tonsillar obstruction and tonsillectomy on facial growth and dental arch morphology. AB - Children, who were tonsillectomized because of sleep apnea were examined with respect to facial growth and dental arch morphology. Dental casts and lateral roentgencephalograms were analysed before surgery and two years after tonsillectomy. The findings were compared to data from children without tonsillary obstruction. A higher proportion of malocclusion than normal, especially open bite and crossbite, was noticed before surgery. Two years after surgery, 77% of the open bites were normalised and 50-65% of the buccal and anterior crossbites. The best results were seen in children operated before the age of 6. PMID- 1743874 TI - Stratified squamous epithelium in relation to the tympanic membrane: its development and kinetics. AB - The pathways of auditory epithelial migration on the human tympanic membrane and their rate of movement were investigated by Hopkins rod photography of dye markings. The origin of these pathways was determined in both the human and the mouse by studying the development of the stratified squamous epithelium of the tympanic membrane and external auditory meatus from earliest embryonic life to maturity. Two pathways of migration are present. In one, epithelium moves from the region covering the tip of the handle of the malleus upwards to the lateral process and then posterior-superiorly with all dye on the pars flaccida to its posterior superior edge. In the second, dye moves centrifugally and radially outwards from the edges of the handle and pars flaccida regions to the annulus. Rate of movement can be determined approximately only and by reference to anatomical landmarks. The first pathway was traced embryologically to migration possibly commencing in the fundus of the primordial first branchial groove. The second pathway has its source in the growth of the meatal plate. A study of the development of the early meatal plate in the mouse suggests that movement of epithelium over the pars tensa region could be the result of a "pulling" effect of mitotically active cells in a generation center at the edge of the tympanic membrane resulting from negative contact inhibition. PMID- 1743875 TI - Bacteriological nasal flora in newborns indicating health and/or development of infection. AB - During delivery, a fetus otherwise sterile during the intrauterine life, comes in contact with bacterial flora of the mother's birth canal, and then also with the ward personnel's skin and respiratory system flora. Due to the absence of competitive bacteriological flora, the nasal cavity is gradually colonized by microorganisms, especially those with a capacity of adhesion to epithelial cells of respiratory nasal mucosa. Bacteriological flora of the newborn's nasal flora was observed on days 1 and 3 postpartum, in an attempt to determine whether a finding of pathogenic bacterial flora in newborn's nasal mucosa indicates a localized infection only or points to the possible development of generalized infection. Bacteriological nasal flora was monitored in infants born by spontaneous delivery and in those born by cesarean section. In mothers of infants born by spontaneous delivery, bacteriological flora from the cervix uteri was investigated. Results of the study performed by usual methods revealed Escherichia coli and Staphylococcus aureus to prevail in the pathogenic flora. Gram-negative microorganisms were found to be good indicators of local infection of newborn's nasal mucosa, regardless of the absence of clinical symptoms. PMID- 1743876 TI - Retrospective study of the prevalence of bilateral sensorineural deafness in childhood. AB - This retrospective study was undertaken to estimate the causes of severe sensorineural deafness (greater than 40 dB HL) in children. The children were identified from case notes of all referrals made to the Children's Hearing Assessment Centre during a 5-year period (from 1st January 1981 to 31st December 1985). Results were tabulated and conclusions drawn following a literature search. It was deduced that following better antenatal screening, a more active immunisation program and improvements in resuscitation of small preterm infants, there was a shift of cases from prenatal to perinatal causes. The proportion of cases of severe sensorineural deafness was much the same as in previous studies. PMID- 1743877 TI - Quality of life issues in chronic otitis media with effusion: parameters for future study. AB - This pilot project studied 61 children with chronic otitis media with effusion. The 12-month period prior to ventilation tube surgery was compared with the 12 months after surgery with respect to numbers of health care visits, the use of antibiotics, parental perceptions of hearing and speech problems, and other selected parameters. Significant decreases were found in total health care visits (mean decrease: 6.18 visits, P less than 0.001). Ear-related health care visits also decreased significantly (mean decrease = 10.93, P less than 0.001). Total health care visits correlated strongly with visits for ear problems both before and after surgery (r = 0.4474, P less than 0.001). Usage of antibiotics significantly decreased. Parental reports concerning the issues of secondary speech and hearing problems raised questions for additional study. In addition, the qualitative comments offered by parents suggest the breadth of impact of chronic otitis media with effusion in this patient population, and point the direction for future research. PMID- 1743878 TI - The two-headed stethoscope: its use for ruling out airway foreign bodies. AB - Foreign body aspiration is a common concern for physicians and surgeons who care for children. Evaluating infants and toddlers to rule out this possible diagnosis is often fraught with difficulties. Specifically, the standard stethoscope is of limited use unless unilateral asymmetry of breath sounds can be appreciated. Inspiratory and expiratory chest X-rays in children often appear to show a very similar diaphragmatic excursion and, unless the object is radiodense, the determination of foreign body aspiration is frequently not possible. Other procedures, such as flexible or rigid endoscopy, are more invasive and are reserved for children with positive findings or a less acute but more perplexing scenario. We present the use of the two-headed stethoscope as an option for evaluation of children to rule out foreign body aspiration. Our experience with this instrument over the past 10 years has consistently allowed us to non invasively differentiate the presence or absence of objects in the airway. PMID- 1743879 TI - A comparison of anterior cricoid split with and without costal cartilage graft for acquired subglottic stenosis. AB - The use of the anterior cricoid split has allowed the extubation of multiple children who would otherwise require tracheostomy. Success, however, has been variable and difficult postoperative complications have occurred. Since 1981, 22 children at the Children's Hospital and Medical Center in Seattle, Washington have failed extubation because of subglottic disease as defined previously by Cotton and Seid. Two approaches have been used in managing the extubation of these children, one employing the anterior cricoid split and one employing the anterior cricoid split with immediate tracheoplasty using costal cartilage grafting. Immediate costal cartilage grafting resulted in fewer complications and a higher success rate in extubating patients with acquired subglottic stenosis. PMID- 1743880 TI - Neurogenic tumours of the parapharyngeal space in the paediatric age group. AB - Two cases of neurogenic tumours of parapharyngeal space in children of 7 years old are presented. Difficulties during the diagnosis, investigations and management are discussed along with a review of the available literature. CAT scan with sialography, carotid angiography during surgery, angle mandibulectomy and liberal incision to expose the great vessels for better control of bleeding are stressed to minimise the peri-operative complication and to assist in complete removal of the tumours. PMID- 1743881 TI - Pharmaceutical industry joins WHO to combat AIDS. PMID- 1743882 TI - Ethical issues in AIDS prevention/control. PMID- 1743883 TI - Why AIDS cannot be transmitted by insects. PMID- 1743884 TI - Carrying the torch for nursing's new tomorrow. PMID- 1743885 TI - Developing nurse managers in Hungary. AB - Success in the work of nursing administrators can be realized only if they have their own sphere of competency and authority. In the Hungarian management system, however, nursing administrators are only functional leaders; they do not have authority for decisionmaking nor do they have a major leadership role. Most hand in proposals and carry out decisions made by the general director/chief physician or other leaders of the hospital. Below, an overview of the present status of Hungarian nursing administrators and a suggested new structure of management that would provide nursing administrators with a full and independent right of decision, which would greatly improve the efficiency of nursing care. PMID- 1743886 TI - Nursing diagnoses of culturally diverse patients. AB - As the world's people become more mobile and the record number of refugees seek new homes, nurses are being increasingly faced with the caring of people from a culture different than their own. More than ever, there is a need for nursing care planned around unique cultural healthcare beliefs, values and practices of patients. However, incorporating cross-cultural defining characteristics into nursing diagnoses has been slow and difficult, the main reason being that nursing diagnoses are built into a classification system based on "labelling" which is "unintentionally culturally insensitive and may even stereotype clients." To help nurses in caring for culturally diverse patients, additions suggested to the classification system of nursing diagnoses are given below. PMID- 1743887 TI - Reflections on an international theory of nursing. PMID- 1743889 TI - The future of neuro-ophthalmology. PMID- 1743888 TI - Promoting assertive behaviours in traditional societies. AB - Nurses have been encouraged to speak out, to exert power and to stand up for their rights as well as the rights of patients. Yet in many cultures strong assertive women are accepted less readily by both men and other women. The question then is: How can nurses in a traditional society be helped to develop assertive behaviours? Based on their experience in Malawi and Nepal, the authors identify the factors influencing nonassertive behaviours and present a model to foster appropriate behaviours in nurses in these and similar countries. PMID- 1743890 TI - Magnetic resonance imaging applications in ophthalmology. PMID- 1743891 TI - Botulinum toxin injections for treatment of blepharospasm and hemifacial spasm. PMID- 1743892 TI - Neuro-ophthalmology: odds and ends. PMID- 1743893 TI - Ocular Lyme borreliosis--1991. PMID- 1743894 TI - Carotid endarterectomy and its alternatives in managing amaurosis fugax. PMID- 1743895 TI - Automated perimetry in neuro-ophthalmology. AB - The automated perimeter presents new challenges to clinicians comfortable with the use of the Goldmann perimeter in neuro-ophthalmic diagnosis. An understanding of the basic differences between kinetic and static threshold perimetry, an intelligent choice of automated test programs, and an interpretive strategy focusing on the vertical meridian will result in optimal use of this important technological advance. PMID- 1743896 TI - Management of nonspecific inflammatory and lymphoid orbital lesions. PMID- 1743897 TI - Optic nerve sheath decompression: history, techniques, and indications. AB - Despite skepticism regarding the efficacy of the procedure, ONSD now has an established role in the management of visual loss associated with chronic papilledema. The surgical procedure requires microscopic dissection of the intraorbital optic nerve to avoid permanent damage to the nerve and its vascular supply. Recent (albeit controversial) investigations concerning ONSD for ischemic disease of the optic nerve suggest that the procedure may have more pathophysiological effects than were once believed. PMID- 1743898 TI - Retinal and optic nerve head disorders masquerading as diseases of the central nervous system. PMID- 1743899 TI - Cultural differences in interpersonal responses to depressives' nonverbal behaviour. AB - The Social Impression and Interpersonal Attraction of British depressed patients was rated by British and German subjects on the basis of the patients' video recorded nonverbal behaviour. Depressives were rated negatively by all subjects. Males in both cultural groups agreed in their ratings of depressives but German females expressed a more negative attitude than British females. This is attributed to cultural differences in sex-appropriate interactive behaviour. The importance of studying the expression of depression and its meaning within a particular cultural context is indicated and the role of cultural differences in interactive behaviour is discussed with respect to intercultural assessment and treatment of depression. PMID- 1743900 TI - Parasuicide and alcohol: a 20 year survey of admissions to a regional poisoning treatment centre. AB - The relationship between alcohol dependence, alcohol consumption and parasuicide was studied among patients admitted over a twenty year period (1968-87) to a regional poisoning treatment centre in Edinburgh. Both alcohol dependence and consumption of alcohol at the time of the parasuicidal act were reported more commonly by men than by women. An examination of temporal trends showed little change among male patients, while the proportion of females diagnosed as alcohol dependent or consuming alcohol at the time of the act tended to increase over time. A comparison of alcohol dependent (AD) and non-alcohol dependent (non-AD) parasuicides over the period 1982-87 revealed differences in respect of sociodemographic characteristics (the AD group containing more unemployed, especially long term) clinical variables (the AD group being more likely to have acted suicidally and to have received psychiatric treatment in the past, yet less likely to be currently diagnosed psychiatrically ill), family features and social problems. The implications of the study findings for research and service delivery are mentioned. PMID- 1743901 TI - Returning for follow up: attendance compliance in an Indian psychiatric clinic. AB - Attendance compliance was studied in first time outpatient attenders at an Indian psychiatric clinic. Compliance was positively associated with the patient's willingness to attend the initial consultation, being given an early appointment time for the first follow up appointment, good work prognosis and informing the patient's accompanying relative of this good work prognosis. Factors associated with decreased compliance were telling the patient the expected duration of treatment and an illness duration of less than six months at the time of presentation. The results have implications for timing of the subsequent appointment, developing rapport with the patient and being circumspect about what the patient is told. PMID- 1743902 TI - DSM-III in the training of British psychiatrists: a national survey. AB - All 223 psychiatric clinical tutors in the UK were surveyed on their use of DSM III in their postgraduate training programmes. Results indicate that DSM-III is widely used in clinical training to some extent in the majority of schemes (73%) and in the schemes where it is used it is rated as moderately useful by nearly everyone (93%). DSM-III is generally perceived to have positive effects on learning basic elements of psychopathology and in offering a common language for diagnostic discussion. Interestingly only 16% of users felt that DSM-III was so complicated that it impeded rather than facilitated the teaching of diagnosis. Few schemes provide specific teaching courses and case conferences provide the major forum for teaching DSM-III. PMID- 1743903 TI - Psychotropic drug prescribing to chronic schizophrenics in a Hong Kong hospital. AB - There is little information on the prescription practice for chronic schizophrenics, especially in Asia. A survey in a mental hospital in Hong Kong revealed a high mean daily dose of antipsychotics and a high frequency of use of anticholinergic drugs. The significance of these findings is discussed. PMID- 1743904 TI - Attitudes of Chinese and American male students towards mental illness. AB - Attitudes towards mental illness were measured by the Opinion About Mental Illness Scale (OMI) for 83 male graduate college students from American and Chinese cultural backgrounds. The OMI questionnaire consisted of five factors: A) Authoritarianism, B) Benevolence, C) Mental Hygiene Ideology, D) Social Restrictiveness, and E) Interpersonal Etiology. Statistically significant differences between the two groups of subjects on Factors A, B, D and E of the OMI were found. American students performed lower on "Authoritarianism", on "Social Restrictiveness", and on "Interpersonal Etiology", and higher on "Benevolence" than Chinese subjects. PMID- 1743905 TI - Marital satisfaction among San Francisco Chinese-Americans. AB - This study investigates variables that predict marital satisfaction in a group of San Francisco Chinese-Americans. Using Campbell, Converse and Rodgers' model of satisfaction as a framework (1976), 41% of the variance of marital satisfaction is accounted for with objective demographics and subjective assessments of marriage components derived from the Locke-Wallace Marital Adjustment Scale items. Chinese-Americans are generally satisfied with their marriage, with men reporting higher satisfaction levels than women. Agreement on life aims and moral behaviour emerges as the most important predictor of marital quality. In addition, for men, agreement in relating to in-laws and friends is also found to be a significant predictor of marriage satisfaction. PMID- 1743906 TI - Experienced Turkish nurses' attitudes towards mental illness and the predictor variables of their attitudes. AB - General attitudes towards mental illness, attitudes towards two vignettes, and possible predictor variables of these attitudes were investigated among experienced Turkish nurses. The analyses showed that the nurses accepted both organic and psychological causation and had rather positive views on drug treatment, psychotherapy, and prognosis. However, they were more favourably disposed towards psychological causation and psychotherapy; the paranoid schizophrenia description was more readily perceived as mental illness and more 'negative' ratings were recorded for this than was the case in the description of neurosis. In terms of predictors, university education was related to lower acceptance of psychotherapy and chances of recovery; older respondents showed higher social distance to the neurosis vignette. The findings were discussed within the context of previous findings from Turkey and other countries. PMID- 1743907 TI - The administration of academic time in a radiology department. PMID- 1743908 TI - Radiotracers and the heart. State of the turf. PMID- 1743909 TI - Malignant hyperthermia. Diagnosis, treatment, genetics, and pathophysiology. PMID- 1743910 TI - Curriculum for musculoskeletal radiology. AB - Although general suggestions have been made regarding a radiology residency curriculum, no specific list of entities has been offered. Over the past ten years, we have developed a resident-run morning conference in musculoskeletal radiology that is supervised by faculty and covers a specific curriculum. We offer our curriculum as an example that may assist other departments in developing their own curricula. PMID- 1743911 TI - Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial. PMID- 1743912 TI - Categorical course approach to resident teaching in cardiac radiology. PMID- 1743913 TI - The fellowship phenomenon. PMID- 1743914 TI - Therapeutic alternatives for subacute peripheral arterial occlusion. Comparison by outcome, length of stay, and hospital charges. AB - Thrombolytic therapy using streptokinase or urokinase has been shown to be a viable alternative to surgical thrombectomy in patients with subacute peripheral arterial occlusion. Urokinase is associated with higher success and lower complication rates than streptokinase, but the cost of urokinase is at least seven times higher. To address questions of utility and effectiveness in the treatment of subacute peripheral arterial occlusions, the authors designed a retrospective study of patients treated either by surgical thrombectomy (n = 70), thrombolysis with streptokinase (n = 19), or thrombolysis with urokinase (n = 22). Outcome of therapy, length of hospital stay, and total hospital charges in the three groups were examined. Treatment successes in the three groups, defined as complete clearing of the occluded segment with patency maintained for 60 days, were 76% for thrombectomy, 32% for streptokinase, and 64% for urokinase. Total duration of hospitalization was 21.1, 21.3, and 11.5 days (P less than .05), respectively. Mean charges for thrombolytic agents were $690 for streptokinase and $6429 for urokinase. Mean total hospital charges, however, were $25,978 for streptokinase, $22,203 for urokinase, and $25,336 for thrombectomy (P = NS). The higher cost of urokinase, then, accounted for the similar total charges, despite the shortened length of stay. These results suggest that urokinase is cost effective compared to streptokinase for subacute peripheral arterial occlusion. Compared to thrombectomy, thrombolysis with urokinase has a marginally lower patency rate at 60 days, but a significantly shorter length of hospital stay. PMID- 1743915 TI - Graded stress radiography of injured anterior cruciate ligaments. AB - Fifty-five patients with clinical suspicion of injury to their anterior cruciate ligament (ACL) were examined by graded stress radiography before arthroscopic verification in an effort to determine the loss of ACL function as a result of ligament tearing. Using a commercially available stress device capable of applying varying pressures to the mid-calf, anterior drawers were measured from lateral radiographs at 0-, 7-, 14-, and 21-kiloPascal pressures and used to calculate the equivalent elastic modulus of the remaining ACL fibers. According to viscoelastic theory, this modulus is proportional to the number of elastically active fibers in the ligament. To verify the validity of this concept, the stress strain relationship of a freshly excised ACL ligament was examined in a tensile testing machine, and the procedure was repeated after the ligament had been partially transsected with a scalpel. Comparison with the elastic modulus of the (intact) ACL of the opposite knee permits an estimate of the percentage of rupture in cases of partial tears. Overstretched ligaments show essentially normal viscoelastic properties once the slack in the ligament has been taken up. Complete tears, on the other hand, show a complete breakdown in the viscoelastic properties of the ACL. The results show that partial tears can be diagnosed by graded stress radiography with a sensitivity of 20% and specificity of 90%. Diagnosis of overstretched ligaments had sensitivity of 50% and specificity of 94%. Complete tears were detected with sensitivity of 88% and specificity of 75% as diagnosed against all other ACL lesions and including normals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743916 TI - Local demineralization as a model for bone strength reductions in lytic transcortical metastatic lesions. AB - The structural consequences of bone density changes associated with lytic metastatic lesions were investigated using an experimental model of regular, lytic metastatic lesions in bone. Circular holes were drilled in the mid diaphyseal cortex of paired adult canine femora. The region around the defect was demineralized in one bone of each pair with 0.8 N HCl. Specimens were tested to failure in four-point bending. Defect size was determined from conventional planar radiographs as the maximum apparent defect diameter divided by the periosteal diameter. Demineralization resulted in irregular defect geometries, which increased the maximum defect dimension 33% to 57% with respect to the original drill hole diameter. Demineralization resulted in additional strength reductions beyond those expected from the original drill hole alone. Despite the irregular demineralization patterns observed, strength reductions were in close agreement with those predicted from data for regular, nondemineralized holes (r2 = 0.93). The results demonstrate that irregular diaphyseal defect borders may not require more complex fracture risk predictors than can be determined from analytic and experimental studies of regular defect geometries. Our results also demonstrate that errors of over 100% can occur when measuring diaphyseal defect size from radiographs that are not optimally aligned with respect to the defect. PMID- 1743917 TI - The prevalence of asymptomatic gallstones in the general population. AB - The gallbladder and biliary system were scanned by real-time ultrasound in 2274 patients undergoing diagnostic ultrasound for other than gallbladder disease. Patients (212) with previous gallbladder symptoms or with nonvisualization of their gallbladder were excluded from the study. Obesity is the most important risk factor for the development of asymptomatic gallstones in women (P less than .01), although it is not a significant factor in men. Increasing age is an important risk factor for both sexes, and the only significant risk factor in men (P less than .01). While few men have asymptomatic gallstones before the age of 40, 5% of women aged 20-29 and 9% aged 30-39 do. In the 40 and over age group, men (14%) and women (11%) had insignificantly different prevalences. In women, the number of previous pregnancies is a significant risk factor (chi-square = 5.4, P = .02). For instance, there is a 3%, 8%, and 17% overall frequency of gallstones in women with 0, 3, and 6 or more previous pregnancies, respectively. A stepwise logistic regression analysis, after adjusting for age, body mass index, and for women, number of pregnancies, found no significant increased risk related to race (P = .40), high blood pressure (P = .43), heart disease (P = .47), or diabetes (P = .46). After age adjustment, there is no significant gender effect (P = .25). Asymptomatic gallstones are a relatively common occurrence in men over 40 and women over 30. While age is the only significant risk factor in men, obesity, parity, and to a lesser extent age were significant risk factors in women. PMID- 1743918 TI - Solid-state phosphorus-31 nuclear magnetic resonance differentiation of bone mineral and synthetic apatite used to fill bone defects. AB - Bioabsorption of synthetic apatite compounds used to promote bone healing and remodeling has been difficult to evaluate. In this study, solid-state phosphorus 31 nuclear magnetic resonance (NMR) has been used to characterize and quantitate bone mineral and a synthetic apatite in order to establish a model for bioabsorption studies. Pulverized solid samples of cortical rabbit bone and a synthetic fluoridated apatite were examined in vitro at variable degrees of hydration. A 9.4 T superconducting spectrometer was used to obtain 31P magic angle spinning NMR spectra and T1 relaxation times. Quantitation was attempted in mixed samples using T1 recovery data. Bone mineral and synthetic apatite could be distinguished by chemical shift and T1 relaxation time in variable hydration states, and were readily differentiated in mixtures by their T1 relaxation time. NMR estimates of relative proportions of components in mixed samples were accurate within 2% of evaluations based on weight. Solid-state 31P NMR therefore provides a suitable method for monitoring the bioabsorption of synthetic apatites. PMID- 1743919 TI - Urine profiles and kidney histology following intravenous diatrizoate and iohexol in the degeneration phase of gentamicin nephropathy in rats. Effects on urine and serum profiles. AB - Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoate induced dysfunction. The excretion of the cytoplasmic enzyme lactate dehydrogenase was significantly greater following iohexol than following diatrizoate. No significant differences between the two media were shown by the various serum components examined. Among the gentamicin-treated rats, light microscopy showed prolonged occurrence of tubular necrosis and a more intensive round cell infiltration following iohexol than following diatrizoate and saline. Both contrast media induced further temporary renal dysfunction in rats with gentamicin nephropathy; iohexol induced more morphologic changes than diatrizoate. PMID- 1743920 TI - In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging. AB - Polylysine covalently linked to moieties of gadopentetate (Gd-DTPA), for use as a macromolecular blood pool marker for contrast material-enhanced magnetic resonance imaging (MRI), was characterized by means of physicochemical measurements and pharmacokinetics in rats and rabbits and compared with Gd-DTPA. Gd-DTPA-polylysine was composed of a series of polymers of different molecular sizes that on average were labeled with 60 to 70 Gd-DTPA moieties (average molecular weight, 48,700 daltons [D]). For the macromolecular compound Gd-DTPA polylysine, relaxivity was three times higher than that of Gd-DTPA. The LD50 value of 17 mmol/kg reflects a fairly high acute intravenous tolerance of the macromolecular compound in mice. Even though the volume of distribution of Gd DTPA-polylysine in rabbits approached the extracellular fluid space (indicating that the macromolecular compound was also leaking slowly into the interstitial space), the half-life of distribution of the macromolecular compound in the extracellular fluid space was significantly prolonged, thus making the compound suitable as a blood pool marker for MRI. In rats the elimination of Gd-DTPA polylysine occurred predominantly via the renal route. High-pressure liquid chromatography-size-exclusion chromatography of the fractionated urine samples revealed that the renal clearance must be the integral sum of the separate clearances of each molecular weight species. No biodegradation of the polypeptide was observed, and biodistribution studies revealed only minimal retention of Gd in the body of the rat. PMID- 1743921 TI - Pharmacokinetics of Gd-DTPA in patients with chronic renal failure. AB - We investigated the pharmacokinetics of dimeglumine gadopentetate (Gd-DTPA), a contrast agent for magnetic resonance imaging (MRI), in 24 patients with chronic renal failure whose creatinine clearance ranged from 7.2 to 70.0 mL/minute (median 25.4 mL/minute). After single intravenous administration of 0.1 mmol/kg, the serum levels of Gd-DTPA were monitored up to five days and urine and feces were collected quantitatively up to two days. The pharmacokinetic parameters were calculated from the concentration-time profile in the serum and urine using an open two-compartment model. No changes in the volume of distribution (Vc and Varea) or in the half-life of distribution were found for patients with chronic renal failure as compared to patients with normal renal function. However, in correlation with the reduced glomerular filtration rate in patients with chronic renal failure, the half-life of elimination was prolonged and serum and renal clearance were decreased. The recovery of Gd-DTPA in urine was 92.1% +/- 12.1% of the dose administered, and extrarenal elimination was less than 0.4%, indicating that glomerular filtration remains the predominant route of elimination. Only for patients with highly impaired renal function (creatinine clearance less than 20 mL/minute) was the recovery in the urine less than complete. PMID- 1743922 TI - A phase I clinical trial with gadodiamide injection, a nonionic magnetic resonance imaging enhancement agent. AB - Twenty adult male volunteers were studied in an unblinded, ascending-dose study to evaluate the safety, tolerance, and pharmacokinetics of intravenously administered nonionic gadodiamide injection. Dosages administered were 0.05, 0.1, 0.2, and 0.3 mmol/kg. Subjects were monitored from 36 hours before, through 72 hours after administration. There were no clinically relevant changes in vital signs or electrocardiograms. No clinically significant changes occurred in blood or urine laboratory parameters, although a tendency for minor, transient elevations in serum iron levels 8 to 48 hours after administration was noted. These changes were not dose-related. Nine of 20 subjects reported at least one adverse event; all events were transient and of mild intensity, the most common being dizziness/lightheadedness and perversion of taste or smell. One subject reported discomfort consisting of mild stinging at the injection site during administration. Gadodiamide was excreted unmetabolized in the urine with greater than 95% recovery at 72 hours after administration. The serum elimination half life was approximately 70 minutes. PMID- 1743923 TI - Preoperative computed tomography for transhiatal esophagectomy. AB - We report the results of a retrospective evaluation of preoperative chest computed tomography (CT) in 50 consecutive patients with esophageal carcinoma confirmed surgically. Forty patients underwent transhiatal esophagectomy without thoracotomy. In ten cases, blunt dissection of the esophageal carcinoma was impossible because of involvement of an adjacent organ. Transhiatal esophagectomy carries lower morbidity and mortality rates than the standard thoracotomy procedure, although long-term survival is considered to be the same with either method. The overall sensitivity of CT in detecting involvement of an adjacent organ, thus contraindicating the transhiatal procedure, was 90%, with an overall specificity of 92%. The positive predictive value was 75%, and the negative predictive value 89%. The negative predictive value of CT for tracheobronchial invasion, the main surgical risk in the transhiatal procedure, was 90%. A negative preoperative CT appears to be a reliable indicator for patients undergoing transhiatal esophagectomy. PMID- 1743924 TI - The effect of a low-osmolar radiographic contrast medium on in vivo and postmortem renal size. AB - High osmolar radiographic contrast media (CM) are known to cause an increase in renal size. To examine the effect of low-osmolar CM on renal size, 14 anesthetized dogs received 12 intravenous bolus injections of 0.5 mL/kg iohexol (541 mOsm/L). The postmortem renal, cortical, and medullary volumes were determined by fluid displacement. Renal volumes of 18 control dogs were determined similarly. The mean (+/- SEM) postmortem renal volumes were 66.1 +/- 2.2 mL for the CM group and 52.3 +/- 3.3 mL for the control group (P = 0.003), whereas the cortical and medullary volumes were similar. Six dogs were also scanned by fast computerized tomography before and after iohexol administration. The in vivo whole renal and medullary volumes enlarged from 67.4 +/- 3.0 to 77.1 +/- 2.8 mL (P = 0.006), and from 28.5 +/- 2.0 to 35.1 +/- 1.1 mL (P = 0.026), respectively, while the cortical volume remained unaltered. These results suggest that even low osmolar CM may significantly increase renal volume, probably by causing tubular expansion. PMID- 1743925 TI - Morphology and growth of the fetal stomach. AB - To assess the development of the fetal stomach, we performed 162 esophageal injections of contrast media into spontaneously aborted normal fetuses from 7.5 to 26 weeks of gestation. The length of esophagus and trunk, greater and lesser curvature, and vertical and oblique axis of stomach were measured, and the means and standard deviations at each gestational age were calculated. The most frequently encountered patterns of stomach shape were: the standard shape, 90%; steerhorn, 3%; and horizontal stomach, 2%. The final shape of the stomach is not assumed at least until the the age of 22 weeks. Regarding the growth of stomach, with age, the greater curvature grew at a much faster rate than the lesser curvature, and the distance between skin and outer border of the stomach increased. The oblique axis of the stomach did not rotate after eight weeks; gastric surface area showed the fastest growth after 14 weeks. The gastroesophageal junction cephalad relative to the trunk ascended through week 25, due to the differential growth of the trunk and esophagus. PMID- 1743926 TI - Identifying drug exposed infants. AB - Better outcome for pregnancy and infant is achieved by identification, intervention and medically appropriate follow up of drug affected pregnancies. Health care professionals should familiarize themselves with the special needs of this special population. PMID- 1743927 TI - Cocaine and pregnant women: a hospital study. AB - How prevalent is cocaine use among pregnant women? This study of pregnant and newborn populations at Broadlawns Medical Center in Des Moines showed positive rates of 7.1% and 3.6%, respectively. The study also showed that accepted risk factors are not reliable indicators of drug use. PMID- 1743928 TI - Iowa's infant mortality: looking worse, doing better. AB - Interstate comparisons of infant mortality data can be misleading unless causes of infant death are considered, says this author. In Iowa the percentage of preventable deaths dropped almost 35% in recent years. PMID- 1743929 TI - Prevalence of fetal alcohol syndrome largely unknown. PMID- 1743930 TI - Fatal pertussis in an Iowa infant. AB - Much media attention has been paid to neurological disease induced by DPT vaccine, but what about the risk of pertussis to unimmunized children? The authors present a case report of fatal whooping cough in a 5-week-old baby. PMID- 1743931 TI - HIV infection in childbearing women. AB - A blinded survey of HIV infection in childbearing women is being conducted in 43 states and territories. After one year of participation in the survey, 6 of 37,846 women bearing live children in Iowa were found to be infected with HIV. PMID- 1743932 TI - In defense of the little ones. PMID- 1743933 TI - Maternal-fetal conflicts. PMID- 1743934 TI - Aldol condensations after Carlo Ricci. PMID- 1743935 TI - Patient Self-Determination Act. Community education. PMID- 1743936 TI - Patient Self-Determination Act. Institutional quandaries. PMID- 1743937 TI - The spirit of the PSDA. Patient Self-Determination Act. PMID- 1743938 TI - Patients, providers, and the PSDA. Patient Self-Determination Act. PMID- 1743939 TI - PSDA in the nursing home. Patient Self-Determination Act. PMID- 1743940 TI - Patient Self-Determination Act. Trumping advance directives. PMID- 1743941 TI - PSDA in the clinic. Patient Self-Determination Act. PMID- 1743942 TI - Patient Self-Determination Act. Honoring broader directives. PMID- 1743943 TI - Patient Self-Determination Act. On behalf of the patient. PMID- 1743944 TI - Oregon update. PMID- 1743945 TI - Of balloons and bicycles--or--the relationship between ethical theory and practical judgment. PMID- 1743946 TI - For experts only? Access to hospital ethics committees. PMID- 1743947 TI - In re Helga Wanglie. PMID- 1743948 TI - When the doctor's on drugs. PMID- 1743949 TI - Zuckerman's dilemma. A plea for environmental ethics. AB - E.B. White's Charlotte's Web serves as an environmental parable for our time. As we reflect on our relationship with nature, we might consider the three ways in which Wilbur the pig was valued in White's story. His instrumental value cashes out in ham hocks and sausage. His aesthetic value earns him a ribbon at the county fair. His moral value is the value he has in and of himself, and Charlotte the spider loves him for it. We can value nature the way Charlotte valued Wilbur, or we can, as the farmer Zuckerman did at first, see the natural world only in terms of the pork chops it provides. PMID- 1743950 TI - Animal ethics reconsidered. PMID- 1743951 TI - Abortion remains a live issue. PMID- 1743952 TI - Fetal tissue research and the misread compromise. AB - The bill to restore federal funding for human fetal tissue research has been passed by the House and awaits Senate approval. But it requires women who are willing to donate fetal tissue to certify that they did not have an abortion with the intent to donate. It further requires researchers to keep the certifications on file and available for government audit. Both requirements spell trouble. PMID- 1743953 TI - Hysterectomy in Scotland, 1961-1984. PMID- 1743954 TI - A new Pick based computer thyroid register based on the national SAFUR requirements for local usage. AB - Patients with thyroid disease require lifelong surveillance to detect late onset hypothyroidism and to monitor thyroid replacement therapy. This is best achieved by a shared-care computer system. We describe the introduction to Tayside (Ninewells Hospital) of a new computerised thyroid follow-up programme based on the Patient Record System under a Pick operating system, run on a Honeywell-Bull minicomputer. This new programme has allowed the transfer of patients from the previous Aberdeen based SAFUR centralised service to a locally based unit, offering an improved, updated and cost effective method for thyroid disease surveillance. Audit, clinical and financial, may now be more efficiently achieved, allowing local needs to direct the service provision. PMID- 1743955 TI - Misplacement in long stay geriatric care, psychogeriatric care and Part IV accommodation. AB - The dependency and behavioural characteristics of 1,461 elderly people in long stay geriatric and psychogeriatric wards and Part IV accommodation were surveyed. Misplacement, defined as having dependency and behaviour characteristics normally associated with admission to another form of care, was widespread, ranging from 5 51% in the different facilities visited. It was greatest in psychogeriatric wards and least in geriatric wards. In Part IV accommodation there was a significant inverse relationship between length of stay and appropriateness of placement. PMID- 1743956 TI - The establishment of a centralised referral service leads to earlier abortion. AB - In 1988 a centralised referral service for termination of pregnancy was established in Edinburgh. This has led to a significant reduction in the time women who have requested termination wait to see a gynaecologist (mean 4.7 days) and in the time it takes before suction termination of pregnancy is undertaken (total wait 10.2 days). In 1988 only 40% of induced abortions in Edinburgh were carried out at 9 weeks gestation or before while in 1989 that figure had risen to 60%. In 1989 less than 10% of pregnancies were terminated at or after 12 weeks gestation, compared with 21% in 1988. Reasons for delays in obtaining an abortion are multifactorial but rapid referral once a woman has made the decision to seek help will be essential if she is to avail herself of the advantages of medical termination--only available until eight weeks of pregnancy. PMID- 1743957 TI - The Chief Scientist reports... The diets of Scottish men and women in relation to nutritional recommendations for health. AB - Diets of middle-aged Scottish men and women were assessed by food frequency questionnaire as part of the Scottish Heart Health Study (a cross-sectional study of risk factors for coronary heart disease (CHD) in 22 regions). The data have allowed evaluation of the diets of different (high CHD risk) sub-groups with respect to nutrient composition and major nutrient sources. This paper summarises the key nutrient source findings by non-manual and manual occupational groups; discusses the Scottish diet in relation to recent recommendations for healthy eating and recommended daily allowances for antioxidant vitamins; and considers ways of achieving dietary change. PMID- 1743958 TI - Alcohol misuse in Scotland--is there a growing health problem? AB - This paper reviews currently available data on alcohol related morbidity and mortality in Scotland. It confirms that admissions to psychiatric hospitals are unlikely to be a reliable indicator of trends in alcohol-related conditions because of the influence of local practice. Discharge rates for general (non psychiatric) hospitals where an alcohol-related diagnosis has been made are reviewed and even using caution in interpreting the data, the results suggest that there is a worrying increase in rates of discharges with an alcohol-related diagnosis. Finally trends in deaths for both alcoholic liver disease (ICD 571.0 3) and unspecified chronic liver disease (ICD 571.4-9) are examined. It is concluded that other indicators of health related harm should be considered. These might include data from those presently seen in out-patient departments with an alcohol related condition as well as patients misusing alcohol who attend their General Practitioner (GP). PMID- 1743959 TI - A framework for the assessment of health care priorities in Scottish health boards. PMID- 1743960 TI - Career paths of physician executives. AB - Survey data from a sample of physicians whose primary professional activity is administration were used to examine their previous administrative positions and career paths. Forty percent reported administrative positions in more than one type of health care organization, and time spent in administration increased with age and years in administration. Most responders with senior titles had four or more positions in a single type of organization or two positions in different types of organizations. These findings should be useful for further investigation on the physician executive role, as well as in career planning. PMID- 1743961 TI - Outcomes measurement: compliance tool or strategic initiative? AB - This article explores how hospitals are using outcomes measurement to deal with their changing environment. Based on interviews at thirty-one hospitals, the study reveals three very different management approaches and three different uses of the same outcomes measurement tool. PMID- 1743962 TI - Analyzing the health care environment: "You can't hit what you can't see". AB - The health care environment of the 1990s promises to be every bit as dynamic and complex as the environment of the 1980s. Health care managers must identify emerging issues and incorporate these issues into the strategic management process. This article discusses a five-step process for analyzing the changing environment facing health care organizations. PMID- 1743963 TI - Codependency: management and administrative policy implications. AB - Health care practitioners may exhibit behaviors that are considered dysfunctional for personal well-being. These behaviors, feelings, and thoughts could affect the manager-employee relations, as well as the implementation of patient care. This discussion focuses on the relevance of codependency in human resource management. Implications of codependency for organizational structure, standards of care, and managerial roles are pointed out. Specific strategies are outlined in recognizing manifestations of codependency. Finally, administrative interventions such as the Employee Assessment and Counseling Programs are suggested to prevent the negative outcomes of codependency which can affect job performance. PMID- 1743964 TI - A managerial approach to costing fixed assets in health care organizations: the role of depreciation and interest. AB - The economic aspect of depreciation and interest on capital are incorporated within a managerial accounting framework by treating both items as imputed charges to be debited to the users of the assets' services. The costs of these services is examined for individual assets that provide either uniform or declining service over the expected life, and for a stock of assets where the character of the individual assets is ignored. By using imputed charges, the hospital's net income is allocated to its sources. PMID- 1743965 TI - Hospital free cash flow. AB - Hospital managers may find it difficult to admit their investments have been suboptimal, but such investments often lead to poor returns and less future cash. Inappropriate use of free cash flow produces large transaction costs of exit. The relative efficiency of investor-owned and tax-exempt hospitals in the product market for hospital services is examined as the free cash flow theory is used to explore capital-market conditions of hospitals. Hypotheses concerning the current competitive conditions in the industry are set forth, and the implications of free cash flow for risk, capital-market efficiency, and the cost of capital to tax-exempt institution is compared to capital-market norms. PMID- 1743966 TI - Hospitals' investment and return from volunteer departments and auxiliaries: evidence from one community. AB - In addition to their nonpecuniary outputs, volunteer and auxiliary programs can make a significant financial contribution to the hospital. Evidence from one community suggests a direct correspondence between a hospital's investment and return from these programs. Hospitals appear to invest little in these activities, however. PMID- 1743967 TI - Health care in the United States. PMID- 1743968 TI - HCMR interview: Richard Johnson. Interview by Montague Brown. PMID- 1743969 TI - Responses to prospective payment by rural New Mexico hospitals. AB - A cross-sectional study is used to determine how rural New Mexico hospitals altered service diversification, inpatient service emphasis, and service promotion during Medicare's prospective payment system (PPS) transition and posttransition phases. Results suggest that the hospitals implemented distinct strategies in response to PPS. The posttransition strategies were examined for their association with improved revenue and utilization indicators. Few of the service diversification and promotional strategies were consistent predictors of performance. Emphasis on fine-tuning inpatient services was the most promising predictor of higher utilization and revenue measures. The implications for other rural hospitals are discussed. PMID- 1743970 TI - Predicting hospital choice for rural Medicare beneficiaries: the role of severity of illness. AB - Previous research has confirmed that desirable hospital attributes as well as increased distance, or travel time, have an impact on hospital choice. These studies have become increasingly sophisticated in modeling choice. This study adds to the existing literature by estimating the effect of both hospital and individual characteristics on hospital choice, using McFadden's conditional logit model. Some patient characteristics have not previously been accounted for in this type of analysis. In particular, the effect of a patient's complexity of illness (as measured by Disease Staging) on the choice of hospital is taken into account. The data consist of over 12,000 Medicare discharges in three overlapping rural market areas during 1986. The hospital choice set was aggregated into seven groups of urban and rural hospitals. Results indicate that rural Medicare beneficiaries tend to choose hospitals with a large scope of service and with teaching activity over those with a lower scope of service and no teaching activity, holding other factors constant. Distance is a deterrent to hospital choice, especially for older Medicare beneficiaries. The more complex cases tend to choose larger urban and rural hospitals over small rural hospitals more often than less complex cases do. PMID- 1743971 TI - Uncompensated care before and after prospective payment: the role of hospital location and ownership. AB - Research was undertaken to determine the effects of hospital ownership, location, and Medicare's prospective payment system (PPS) on inpatient uncompensated care. A nonequivalent group design was used with repeated measures of uncompensated care (UNCC) on 137 system hospitals taken pre- and post-PPS. Investor-owned system hospitals demonstrated the largest increase in UNCC (37 percent) under the PPS. Results suggest that not-for-profit and investor-owned system hospitals are becoming more similar in levels of uncompensated care provided and that the PPS has had a negative effect on rural hospital profitability. PMID- 1743972 TI - Nursing home costs, Medicaid rates, and profits under alternative Medicaid payment systems. AB - This analysis compares nursing home costs, Medicaid payment rates, and profits under three Medicaid nursing home payment systems: case-mix, facility-specific, and class-rate systems. Data used were collected from 135 nursing homes in seven states. The association of case mix with costs, rates, and profits under the three payment systems was of particular interest. Case mix was more strongly associated (positively) with patient care cost and the Medicaid rate for the case mix systems than for the other systems, particularly the class-rate systems. In contrast, case mix and profits were not associated in the case-mix or facility specific systems, but were negatively associated in the class rate systems. Overall, the results suggest that case-mix systems have some important advantages over other payment systems, but further research is needed on larger samples and involving the newer case-mix systems. PMID- 1743973 TI - Using medical care: the views and experiences of high-risk mothers. AB - Two recurrent unsolved problems of health services practice and policy in modern industrial countries are those of social class inequalities and user dissatisfaction. This article presents data related to these issues drawn from a sample of British childbearing women deemed "at risk" by health professionals. A third focus is on the relationship between past experiences of maternity care, and the patterns of service provision and perceptions of needs and satisfaction revealed in a subsequent pregnancy. Findings show a tendency for patterns of care to be differentiated by social class, with working class women generally receiving comparatively poor service. Satisfaction with general practitioner (community-based) prenatal care is higher than with hospital care. The more socially disadvantaged women in the sample are more likely to be dissatisfied with their medical care. The three major pregnancy needs highlighted by the sample women are for more continuity of care, more sympathetic medical care, and help with household finances. Adverse previous childbearing experiences are related to more dissatisfaction in the subsequent pregnancy. PMID- 1743975 TI - Cribs. AB - We evaluated four cribs with adjustable mattress supports from four manufacturers. Three of the units are rated Acceptable, and one unit is rated Conditionally Acceptable--it is Acceptable on the condition that it is purchased without its semidetachable slat option. We describe the rationale behind our Evaluation in the Introductory Comments below. And in the Crib Assessment and Purchasing Guide, which follows the Conclusions and Ratings, we provide general guidance to help readers evaluate cribs that were not included in this study. PMID- 1743974 TI - Factors associated with hospitalization in a sample of chronic hemodialysis patients. AB - This study examines the hospitalization experience of a sample of chronic hemodialysis patients, using primary data sources. There were multiple causes of hospitalization over the six-month tracking period, with stays extending from 1 to 87 days. Patients were more likely to be hospitalized if they had a negative hepatitis antigen, lower functional status scores, lower phosphate and protein levels, repeated access procedures, other cardiovascular conditions, arthritis, psychiatric disorders, ischemic peripheral vascular disease, lung disease, or larger households. Hospitalization for access-related problems was associated with arthritis, previous access procedures, and blood pressure levels. Sociodemographic and treatment characteristics did not have a significant influence on the risk of hospitalization. Improved management in these clinical areas may improve the quality of life of chronic hemodialysis patients and reduce the high level of expenditures associated with delivering inpatient services to this segment of the Medicare population. PMID- 1743976 TI - Infrared ear thermometry. AB - Many hospitals are considering using infrared (IR) ear thermometers (also called tympanic membrane thermometers) as an alternative to traditional temperature measurement devices. IR technology allows users to quickly and noninvasively measure body temperature by inserting a directional probe into the ear canal. For infection control, ear thermometers offer the advantages of not contacting mucous membranes and eliminating the need for special handling procedures. For use on unconscious patients or those who are otherwise unwilling or unable to cooperate with traditional techniques, IR ear thermometers offer a more comfortable and less stressful method of temperature taking for both patients and nurses, especially where rectal temperatures are used. The recent entry into this market by major companies and distributors and the release of several new IR ear thermometers have helped to further stimulate interest in this technology. However, a complete transition to IR ear thermometers throughout the hospital may not be necessary and should be made only after these devices have been successfully used in selected clinical locations, such as emergency departments, critical care areas, recovery areas, and labor and delivery rooms. Clinical users must be familiar with the technique needed for temperature measurement with these instruments and understand the differences between temperatures taken in the ear canal and those obtained from traditional sites. In the following article, we first present and overview of clinical thermometry, describing traditional temperature-measurement sites and devices. We then discuss the advantages and disadvantages of using the ear canal, including the tympanic membrane (TM), as a site for temperature measurement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743977 TI - Rubber universal breathing-circuit adapters: risk of increased disconnections. PMID- 1743978 TI - Xomed laser-shield endotracheal tubes: flammable tubes still being used. PMID- 1743979 TI - COULTER lyse S IIIdiff: reagent lot gives erroneous results. PMID- 1743980 TI - Stryker surgical microsurgical drills: activation by ESUs. PMID- 1743981 TI - Positron emission tomography in the investigation of neuropsychiatric disorders: update and comparison with magnetic resonance imaging and computerized tomography. AB - In many neuropsychiatric disorders, PET imaging offers functional insights unavailable from anatomic imaging alone. Functional deficits may be more extensive than structural findings would indicate, may occur before the detection of anatomic changes, or may even occur in the absence of any structural lesions. We contrast the current role of PET with that of MRI and CT in the investigation of neuropsychiatric disorders including stroke, tumor, head trauma, epilepsy, schizophrenia, movement disorders, normal aging and dementia. PMID- 1743982 TI - The role and rationale of nuclear medicine procedures in the differential diagnosis of renovascular hypertension. AB - The use of radionuclides in the differential diagnosis of renovascular hypertension has gone through many periods of enthusiasm and of disappointment. Regardless of the problems with the routine renogram, the availability of gamma camera renal evaluation makes possible meaningful preintervention of screening. The use of the test as a follow-up procedure is an extremely important but often overlooked application of radionuclides in the evaluation of renovascular hypertension. The radionuclide technique is a sensitive and accurate method of evaluating the results of percutaneous angioplasty or surgery or renal function in the affected kidney of patients with renovascular disease. A major change in our approach to the nuclear medicine diagnosis of renovascular hypertension has been the introduction of captopril renography. Although there is still a great deal of work to be done and many investigators are actively studying captopril renography, the potential of the test is clear. Captopril renography should include a baseline renogram, followed by the administration of 25 mg of captopril and a repeat study. Specificity and sensitivity data on this test probably will not be available for several years, but preliminary results are encouraging enough to justify routine use at this time in clinics in which screening for renovascular hypertension is carried out. PMID- 1743983 TI - Progress in research on ligands, nuclides and techniques for labeling monoclonal antibodies. AB - This paper reviews the current methods for radiolabelling monoclonal antibodies with particular emphasis on radiometals useful for radioimmunoscintigraphy. The discussion, however, is equally applicable to therapeutic radionuclides. The advantages and the pitfalls of the various techniques are critically evaluated. Both direct labeling methods, as well as indirect methods using the bifunctional chelating agent approach, are covered. Recent work on the development and synthesis of new and more specific chelating agents, including the approach of utilizing rigid polyaminocarboxylates, is described. Preliminary promising results with these newer generation chelating agents are presented. PMID- 1743984 TI - Technetium-99m-labeled proteins for imaging inflammatory foci. AB - Polyclonal human IgG (IgG), antinuclear antibody (TNT-1), and human serum albumin (HSA), were labeled with 99mTc by a method recently developed in our laboratory, and administered i.v., each to a separate group of five mice, bearing inflammatory foci induced by an i.m. injection of 40 microL turpentine or 5 x 10(8) E. coli and 5 x 10(8) Entercocci. TNT-1 labeled with 125I served as a control and 67Ga-citrate as a "gold standard". At 4 or 24 h post injection, animals were imaged and sacrificed for tissue distribution studies. At 4 h in the turpentine group, the abscess-to-muscle ratios were: 67Ga, 4.8 +/- 2.1, 125I-TNT 1, 4.3 +/- 1; 99mTc-TNT-1, 3.5 +/- 1.8; 99mTc-IgG, 3.9 +/- 0.6; and 99mTc-HSA, 4.3 +/- 1. In the microorganism group, these ratios were 2.6 +/- 0.6, 3.3 +/- 0.5, 3.4 +/- 0.08, 3 +/- 1.1 and 4.1 +/- 0.6, respectively. Autoradiographic examination of infected tissues indicated that leakage of labeled proteins into interstitial space due to increased capillary permeability may be one of the major mechanisms of uptake. PMID- 1743985 TI - Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy. AB - L-6, a mouse IgG2a anti-adenocarcinoma monoclonal antibody (MoAb) with favorable immunopathology and mouse biokinetics, was evaluated for cancer radioimmunotherapy by pharmacokinetic studies in 10 patients with breast cancer. The effect of escalating the preinfused protein dose was studied in two patients at each level, using 50, 100, 150, 200 and 400 mg of unlabeled L-6 prior to a 10 mCi imaging dose of 131I L-6. Quantitative imaging, and blood and urine clearances were obtained. After the 50 mg preinfusion, rapid blood clearance and lung extraction of the radiopharmaceutical occurred immediately post injection. Greater preload amounts of L-6 were associated with an increase in the intercept of the slow phase of the blood clearance from 17 to 22% injected dose (ID) with 50 mg to 70 to 80% ID with 400 mg (P less than 0.01). Lung uptake of the radiopharmaceutical immediately post injection decreased from 15 to 19% ID (50 mg) to 6 to 8% ID (400 mg). Tumors were visualized only after larger L-6 preloads, but in these patients small chest tumors contained 0.6-1.2% ID (0.1% ID/g maximum). This study suggests that L-6 reactive sites that are readily available in the lung can be saturated, so that a subsequent dose of I-131 L-6 is delivered to the tumor. This approach provides a new strategy for developing an effective method for radioimmunotherapy using a MoAb that has some cross reactivity. Quantitative imaging contributed to detection of the cross-reactivity and the strategy for overcoming it. PMID- 1743986 TI - Strategies for enhancement of radioimmunotherapy. AB - Two new strategies for increasing tumor uptake have been investigated. First the effect of interleukin-2 (IL-2) on tumor uptake of 125I-Lym-1 antibody in nude mice was investigated. Secondly, the use of 67Cu-labeled Lym-1 was evaluated in patients. In nude mice implanted with Raji human lymphoma, a greater than 2-fold enhancement of tumor uptake of 125I-Lym-1 was observed after administration of PEG-interleukin-2 (PEG-IL-2). The macrocycle 1,4,8,11-tetraazacylcotetradecane N,N',N",N"'-tetraacetic acid (TETA), synthesized specifically for copper chelation, has been conjugated to Lym-1 for 67Cu labeling of the monoclonal antibody (MoAb). There was no evidence for bone or normal marrow uptake and the residence time in the tumor was prolonged. Surprisingly, a dose of 4.4 mCi that was intended for imaging induced substantial tumor regression in a patient. PMID- 1743987 TI - Radionuclide assessment of blood-brain barrier disruption performed for chemotherapy of high grade malignant brain gliomas. AB - Compared to the conventional mode of chemotherapy of malignant brain gliomas following surgery and radiation therapy, chemotherapy after transient disruption of the blood-brain barrier coupled with intraarterial administration of methotrexate improved median survival from 12-14 to 22 months in our experience. Technetium-99m-DTPA brain scintigraphy played a unique and important role in the documentation of optimum blood-brain barrier disruption. Patients with excellent clinical outcome had significantly (P less than 0.0005) better blood-brain barrier disruption than patients with poor outcome. The results indicate that the clinical outcome is related to the degree of blood-brain barrier disruption. PMID- 1743988 TI - Recent developments in 99mTc and 123I-radiopharmaceuticals for SPECT imaging. AB - Availability of 123I of high radionuclidic purity has encouraged the development of 123I-based radiopharmaceuticals for the assessment of myocardial fatty acid metabolism, myocardial neuronal activity, and for receptor and antibody imaging. Advances in the chemistry of technetium have resulted in the development of novel agents for myocardial and cerebral perfusion and renal function studies. Monoclonal antibodies labeled with 99mTc show promise for imaging neoplastic lesions, myocardial infarcts, and thrombus localization. Recent developments in 123I and 99mTc agents for myocardial and brain imaging studies are discussed. PMID- 1743989 TI - Radionuclide methods of detecting acute gastrointestinal bleeding. AB - It is clinically very important to localize the bleeding site in suspected patients. Current common diagnostic methods are endoscopic, angiographic, and radionuclidic. Of the noninvasive procedures, 99mTc-RBC and 99mTc-colloid methods have gained wide popularity. In our series of a comparative study, the RBC method has been shown to be more accurate than the colloid method. The 99mTc-RBC method should be available as a routine emergency procedure in every large clinical center. PMID- 1743990 TI - Assessment of lysosomal function by quantitative histochemical and cytochemical methods. AB - Quantitative histochemistry and cytochemistry enables a direct link to be made between metabolic functions such as the activity of lysosomal enzymes and the morphology of a tissue or a type of cell. Several approaches exist such as microchemistry based on (bio)chemical analysis of a single cell or a small piece of tissue dissected from a freeze-dried section. This technique has been routinely used for prenatal diagnosis of inherited enzyme defects and especially of lysosomal storage diseases. Other approaches are cytofluorometry or cytophotometry, which are based on the principle that a fluorescent or coloured final reaction product is precipitated at the site of the enzyme. The amount of final reaction product is analysed per cell or per unit volume of tissue using either a microscope cytofluorometer or flow cytometer for fluorescence measurements or an image analysing system or scanning and integrating cytophotometer for absorbance measurements. In principle, fluorescence methods are to be preferred over chromogenic methods because they are more sensitive and enable multiparameter analysis. However, only a limited number of fluorogenic methods are at hand that give a final reaction product which is sufficiently water-insoluble to guarantee good localisation. The best results have been obtained with methods based on naphthol AS-TR derivatives and with methods for the demonstration of protease activity using methoxynaphthylamine derivatives as substrates and 5'-nitrosalicylaldehyde as coupling reagent. Chromogenic methods are far better with respect to localisation properties and, therefore, most commonly used for quantitative histochemical analysis of lysosomal enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1743991 TI - The role of lysosomes in hyaline droplet nephropathy induced by a variety of pharmacological agents in the male rat. AB - The male rat is prone to hyaline droplet formation in renal proximal tubular cells. Several unrelated pharmaceutical agents exacerbate the formation and accumulation of these droplets. Where the loading of the proximal tubular cells is marked it gives rise to increased cell turnover and a hyaline droplet nephropathy develops. Cytochemical procedures, have confirmed that this accumulation of hyaline droplets represents an increase in the size and number of secondary lysosomes involved in protein uptake and metabolism. This predisposition of the male rat to develop hyaline droplet nephropathy relates to (1) the large amounts of the low-molecular-weight protein alpha 2U globulin in the glomerular filtrate, (2) the resistance of the globulin to proteolysis, and (3) the low protease activity in the proximal tubule lysosomes. The current data would suggest that the pharmacological agents, which cause the nephropathy, exert their effect by reducing the proteolytic breakdown of alpha 2U globulin in the proximal tubule lysosomes. This results in the overloading of a system which is already operating near maximal load. Female rats, and all other species excrete only small amounts of alpha 2U globulin or similar proteins, which are more easily hydrolyzed. Thus it is argued that the type of hyaline droplet nephropathy induced by these pharmacological agents is unique to the male rat and of little relevance to man. PMID- 1743992 TI - Immunocytochemical and labelled tracer approaches to uptake and intracellular routing of immunoglobulin-G (IgG) in the human placenta. AB - Isolated lobules of freshly delivered human term placenta were (a) subjected to an indirect immunoelectron ultracryo method in which the immunoreactivity of endogenous Immunoglobulin-G (IgG) to rabbit anti-human IgG antibody was localized with protein-A-colloidal gold and (b) extracorporeally perfused and human IgG molecules complexed to horseradish peroxidase (HRP) added to the maternal perfusate and the uptake of IgG-HRP over different perfusion durations visualized ultrastructurally by using diaminobenzidine cytochemistry. Immunoreactivity to anti-human IgG antibody was localized all along the apical plasmalemma, in apical coated and uncoated vesicles, in apical and juxtanuclear multivesicular bodies, and in basal vesicles of the syncytiotrophoblast layer of the placenta. The stroma separating the syncytiotrophoblast from the foetal endothelium as well as vesicles within the endothelium were immunoreactive. No immunoreactivity was localized in paracellular clefts of endothelia. A similar distribution of exogenous IgG-HRP was observed for the perfused placentae. When bovine IgG-HRP or HRP alone were used as control tracers no uptake was seen for the former whilst the latter was observed only in early endosomal vesicles of the syncytiotrophoblast. The pattern of localization visualized in both studies is consistent with receptor-mediated uptake of IgG by the syncytiotrophoblast and a vesicular transport of IgG across the foetal endothelium. PMID- 1743993 TI - Predicting the behaviour and selectivity of fluorescent probes for lysosomes and related structures by means of structure-activity models. AB - Cultured rat fibroblasts were exposed to 50 fluorescent probes of varied physicochemical characteristics. Probe concentrations, fluorochrome excitation wavelength and period of illumination, and cell-probe contact time were varied. Structure-activity relationships defining a number of classes of fluorescent probes for lysosomes and related processes and compartments were demonstrated. Numerical specifications are now available for several familiar classes of probes: (a) acidotropic weak bases, used as markers for low pH compartments; (b) markers of adsorptive pinocytosis, involving non-specific protein binding; (c) markers for fluid phase pinocytosis; and (d) viability stains involving intralysosomal enzymic activity. Two novel classes of probes have also been specified numerically: (a) acid-precipitated weak acids, as markers for low pH compartments; and (b) lipid-binding markers of adsorptive pinocytosis. Overall, these structure-activity models provide a tool for predicting whether or not compounds enter cells; and whether they accumulate in lysosomes and related compartments. Pathways of entry are also predicted. This tool should permit design and selection of improved probes, and provide a better understanding of existing reagents. Moreover these models are expected to be applicable to interactions between any non-polymeric xenobiotic with lysosomes and related compartments. PMID- 1743994 TI - Energy depletion and autophagy. Cytochemical and biochemical studies in isolated rat hepatocytes. AB - In this paper, data dealing with the sensitivity of autophagy towards partial ATP depletion in isolated rat hepatocytes are reviewed. Partial reduction of intracellular ATP causes: (1) a decrease of proteolytic flux; (2) a decrease in uptake of cytosolic components into the autophagic-lysosomal compartment; (3) either a decrease or no change in the ratio between volume densities of autophagosomes and lysosomes, depending on whether or not the cytosolic phosphate potential is affected; and (4) impairment of the lysosomal proton pump. It is concluded that the consecutive steps of autophagy all respond to relatively small changes of intracellular ATP concentration. PMID- 1743995 TI - A quantitative immunoelectronmicroscopic study on soluble, membrane-associated and membrane-bound lysosomal enzymes in human intestinal epithelial cells. AB - We have used quantitative immunoelectronmicroscopy to compare the in situ localization of acid alpha-glucosidase, lysosomal acid phosphatase, beta hexosaminidase and glucocerebrosidase in intestinal epithelial cells of the human duodenum. Differences between these four lysosomal enzymes were observed with respect to their presence at the apical cell surface. Transport to the apical membrane seems to be a more important intracellular route for lysosomal acid phosphatase and acid alpha-glucosidase than it is for beta-hexosaminidase. The membrane associated lysosomal enzyme glucocerebrosidase is not transported to the microvilli. The studies emphasize that lysosomal enzyme transport pathways are enzyme and cell type specific. PMID- 1743996 TI - Localization of lysosomal antigens in activated T-lymphocytes. AB - The lysosomal compartment has been examined in activated T-lymphocytes by immunogold electron microscopy and subcellular fractionation. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of radiolabelled extracts of the T-cells showed that they contained three antigens which are fundamental to normal lysosomal function: a representative lysosomal enzyme beta-glucuronidase, a lysosomal associated membrane protein (LAMP-1), and the cation-independent mannose 6-phosphate lysosomal enzyme targeting receptor (MPR). Immunogold labelling showed that beta-glucuronidase was present in the rough endoplasmic reticulum, the Golgi complex and Golgi-associated vesicles. The enzyme was also found to accumulate in distinct, non-Golgi organelles in which LAMP-1 was co-localized, probably lysosomes. LAMP-1 was also found in tubular elements of the Golgi and in a complex of vesicles clustered near the nucleus where MPR was also present at high density. Fractionation of homogenates from lymphocytes on Percoll gradients revealed that beta-glucuronidase was distributed throughout the low density region containing rough endoplasmic reticulum, Golgi and plasma membrane components, and the high density region which contained only lysosomal activity. Multiple immunogold electron microscopy of the latter fraction showed the presence of homogenous vesicles which had large amounts of beta-glucuronidase within the lumen, LAMP-1 at the periphery and no MPR. These vesicles were probably mature lysosomes, arising from pre-lysosomal organelles enriched for LAMP-1 and MPR. PMID- 1743997 TI - Catalytic histochemistry of acid and neutral hydrolases in plant seedlings. AB - In contrast to human and animal tissues, little information is available on the activity, distribution and functional role of acid and neutral hydrolases in plant cells and tissues. Because it is known that these enzymes are relatively active during germination, they were analysed histochemically during this process using light microscope azo, azoindoxyl, indigogenic and tetrazolium methods. Proteases, glucosidases and glucuronidases could not be detected. Non-specific acid phosphatases were species-independent and showed considerable activities in aleuron and nutritional cells, in other cell types of cotyledon or endosperm tissue and in different types of embryonic cells. Acid glycosidases and non specific esterases, in contrast, displayed a species-dependent activity and differences in localization. Of the glycosidases, alpha-D-galactosidase was the most active. Non-specific esterases, acid phosphatase and glucosaminidase were also present in the extracellular matrix. During germination, acid hydrolase activity either decreased or increased, depending on the seedling species and enzyme. PMID- 1743998 TI - Uptake of horseradish peroxidase by human oesophageal explants over 24 h. AB - Human oesophageal biopsies, endoscopically and histologically normal, were incubated in Ham's F10 for periods up to 24 hours in the presence of horseradish peroxidase. The fluid phase marker was taken up most avidly by the prickle cells but to a lesser extent in the functional layers and by basal cells. Endocytosed markers proceeded to multivesicular bodies (segrosomes). Horseradish peroxidase was later deposited in lysosome-like structures and also in the Golgi apparatus. The lesser uptake by the functional cells may represent reduced access of the marker to the cells due to the intercellular barrier. PMID- 1743999 TI - Electron microscopical demonstration of thiols and disulphides in the porcine epidermis. AB - This study describes the electron microscopical distribution of free thiols and disulphides in the epidermis of the domestic pig and the wild boar, as compared to light microscopical histochemistry. With the silver methenamine method, silver labelling of thiols was clearly achieved on the keratohyalin and cytofilament accumulations in the cells of the living epidermis and the plasma membrane of granular cells. To a certain extent, the envelope and cytoplasm of young corneocytes reacted equally intensively. Disulphides were very abundant in the filaments, keratohyalin granules, and cell envelope of granular cells, and, particularly, in the envelope (marginal band) of corneal cells; the latter structure being distinctly delineated from the background. As a specific feature, the viable epidermis of the wild boar stained strongly for disulphides. The results obtained are discussed in view of actual concepts of epidermal keratinization and corneal cell function. PMID- 1744000 TI - Characterization of an expressible nonclassical class I HLA gene. AB - Screening of a human cosmid library representing genomic DNA from an individual homozygous for the HLA-DR2 B7 A2 haplotype yielded 109 class I HLA-specific clones. One cosmid clone, Ice 6.23, had a full-length nonclassical class I gene within a 5.4-kb HindIII fragment. The Ice 6.23-5.4H gene was cloned into the unique NotI site of an expression vector pSV2.Not, a derivative of pSV2neo, which was constructed to contain a second SV40 early region promoter adjacent to an introduced NotI site. The resulting construct was transfected into the P815-B2M cell line, a derivative of the mouse mastocytoma P815 (HTR) line which expressed human beta2-microglobulin following stable transfection with a cloned human beta2 microglobulin gene. Following transfection the Ice 6.23-5.4 H gene was found to be expressed at both the mRNA and cell surface product levels. DNA sequencing of this gene suggests that it is allelic to the HLA-6.0 gene clone (HLA-G) of Geraghty et al. (Proceedings of the National Academy of Sciences USA, 84:9145, 1987); thereby revealing a HindIII restriction fragment length polymorphism at the HLA-G locus. An extraordinarily high degree of sequence similarity (99.92%) between these two genes, which derive from unrelated HLA haplotypes, suggests strong conservative selection pressure at the HLA-G locus. A flanking single copy sequence probe 4 kb distant from the Ice 6.23-5.4H gene was used to generate long range restriction mapping at the HLA-G locus. PMID- 1744001 TI - Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition. AB - The relative contributions of putative T-cell receptor (TCR)-contacting and peptide-binding residues of a major histocompatibility complex (MHC) class II restriction element to serologic and antigen-specific T-cell recognition were investigated by site-specific mutagenesis. Amino acids 70 and 71 in the DR beta 1 domain of DR4 Dw10 are uniquely differnet from the other Dw subtypes of DR4. Residue 70 is predicted to be located at the membrane-distal surface of the class II molecule, where it may influence T-cell recognition by a direct interaction with a TCR. Residue 71 is predicted to form part of the antigen-binding groove where its influence on T-cell recognition may be mediated indirectly via an effect on peptide binding. Transfected murine L cells were produced expressing the products of DR4 Dw10B genes in which the codons for residues 70 and 71 had been mutated towards DR4 Dw14. Support for the predicted orientations of beta chain residues 70 and 71 was lent by the observation that only residue 70 plays an important role in the formation of a serologic determinant. Mutation of this residue was sufficient to produce recovery of recognition by a human monoclonal antibody, NI, which has specificity for all the DR4 subtypes with the exception of DR4 Dw10. The human T-cell clone HA1.7, specific for influenza virus hemagglutinin (HA) peptide 307-319 and restricted by DR1 Dw1, exhibits degeneracy of MHC restriction on the DR4 Dw subtypes with the exception of DR4 Dw10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744002 TI - Immunochemical analysis of a recombinant, genetically engineered, secreted HLA A2/Q10b fusion protein. AB - We engineered a fusion gene which encodes the alpha 1 and alpha 2 domains of HLA A2 with the alpha 3 and truncated transmembrane domains of the murine class I like protein Q10b, and transferred it into mouse L cells along with the gene for human beta 2-microglobulin (beta 2m). The secreted rA2/Q10b gene product consisted of a single heavy chain of molecular weight 42 kd that was noncovalently associated with the human beta 2m light chain. Native detergent solubilized HLA-A2 and secreted rA2/Q10b proteins were found to be similar by: (a) the binding to mouse monoclonal anti-HLA antibodies in an ELISA; (b) the blocking of lysis of HLA-A2+ cells by human anti-HLA-A2,-B17, anti-HLA-A2,9,28, and anti-HLA-A2,28 cross-reactive group (CREG) antisera in a complement-dependent cytotoxicity assay; and (c) the ability when coupled to Sepharose to selectively purify HLA-A2,9,28 and HLA-A2,28 CREG-specific antibodies. Mouse L cells expressing rA2/Q10b produced as much as 2.5 micrograms protein per 10(6) cells/day, or 50- to 100-fold more antigen on a per cell basis than the level of HLA-A2 expressed by B-lymphoblastoid cell line or spleen cells. Thus rA2/Q10b represents a viable alternative to detergent-solubilized HLA-A2 for purification of anti-HLA-A2 antibodies and analysis of anti-HLA-A2 immune responses. PMID- 1744003 TI - DRw11 haplotypes: continuum of DRB1 diversity augmented by unique DQ/DRw52 associations. AB - cDNA sequencing of the first domains of DRB1, DRB3, DQA1, and DQB1 alleles was used to examine the extent of diversity in American black individuals expressing several DRw11 haplotypes. In addition to previously described DRw11 alleles, DRB1*1102 and DRB1*1103, two new DRB1 alleles, DRB1*11012 and DRB1*11042, were identified which differ from previously described alleles at the nucleic acid but not at the protein level. Gene conversion-like events have likely generated the DRw11 microvariation resulting in the merging of DRw11 with the DRw13 allele family. The DRw11 alleles are associated with various DQ alleles: DQw1 (DQw5 and DQw6), DQw7, and a serologically undefined DQ allele. This undefined DQ molecule, comprised of a DQ alpha/beta combination encoded by a DQw7 alpha gene (DQA1*0301) and a DQw2 beta gene (DQB1*0201), was previously observed in some DR7 and DR9 haplotypes. DRw11 haplotype diversity is augmented by the association of one of the DRw11 alleles with the DRw52c allele in contrast to the more common DRw11, DRw52b association. The extensive diversity exhibited by the DRw11 and DRw13 family of haplotypes coupled with their high frequency in populations of African ancestry suggest that the DRw11/w13 allele family may be very old and/or that these haplotypes carry some selective advantage. PMID- 1744005 TI - The cost of treating patients infected with the human immunodeficiency virus (HIV) in the United States. PMID- 1744004 TI - Effect of HLA phenotype and gender on expression of various forms of class I HLA in plasma. AB - To understand the complexity of plasma HLA antigens, the distribution of different molecular weight forms of class I HLA in plasma was investigated in 44 HLA-phenotyped and unrelated individuals. Plasma class I HLA were immunoprecipitated by using the W6/32 anti-HLA monoclonal antibody, separated by SDS-polyacrylamide gel electrophoresis and characterized by immunoblotting with the HC-10 monoclonal antibody. Four different forms of HLA heavy chains (HLA-HC) with relative molecular masses of 44, 39, 36, and 34 kd were detected. Plasma samples from all individuals contained 44 and 36 kd HLA-HC, but varied as to the presence of 39 and 34 kd HLA-HC. Eighteen percent of the individuals did not have any detectable class I HLA with 39-kd heavy chains in their plasma and 61% did not have plasma class I HLA with 34-kd heavy chains. Thus, four different distribution patterns were identified for plasma class I HLA among all individuals included in our study. The distribution patterns in four different individuals were evaluated quarterly and remained unchanged during 1 year follow up. A significant association of absence of 39-kd plasma class I HLA-HC with female gender (p less than 0.05) and HLA-B7 phenotype (p less than 0.00015) was also found. Further pedigree analyses of four families of HLA-B7-positive and 39 kd HLA-HC-negative probands indicated that genetic factor(s) other than those associated with HLA-B7 allele and female gender is involved in regulating the expression of the plasma class I HLA with 39-kd heavy chains. PMID- 1744006 TI - Osteopathic medical educators should heed lesson from interns. PMID- 1744007 TI - Cutaneous immunopathology of androgenetic alopecia. AB - Male pattern baldness is assumed to result from a combination of normal serum concentrations of androgen and an appropriate genetic background. To study whether inflammation contributes to the development of androgenetic alopecia, direct immunofluorescence and dermatopathologic studies were performed on biopsy specimens from bald scalp of patients, with specimens from uninvolved scalp of these patients or from scalp of volunteers who were not bald serving as controls. Granular deposits of Immunoglobulin M or C3 (or both) were found at the basement membrane in 25 (96%) of 26 study patients and 1 (12%) of 8 control subjects. Granular C3 was also deposited on eccrine myoepithelial cells in 8 (31%) of 26 study patients, but no control subjects. Porphyrins were found in the pilosebaceous canal in 15 (58%) of 26 study subjects and in 1 (12%) of 8 control subjects. These results support an inflammatory pathogenesis of androgenetic alopecia. Propionibacterium acnes is known to produce porphyrins. Ultraviolet radiation may excite microbiologic porphyrins that could activate C3 and, subsequently, the complement cascade producing inflammatory mediators. PMID- 1744008 TI - Dementia in patients with the acquired immunodeficiency syndrome. AB - Central nervous system (CNS) manifestations are common in patients with the acquired immunodeficiency syndrome (AIDS). The most common CNS syndrome is a dementing illness referred to as the AIDS dementia complex, in which motor and cognitive changes may also be seen. Neurodiagnostic studies are fairly characteristic, though highly nonspecific. Dementia may precede overt manifestations of AIDS, and either an insidious or a fulminant course may be seen. Appropriate management of the patient with AIDS includes differentiating dementia from psychologic responses to the disease. PMID- 1744009 TI - Blood ethanol testing. AB - The justification for blood ethanol testing springs from the ubiquitous abuse of alcoholic beverages. Those dealing with patients who abuse alcohol must understand the correlations between dose, time, blood level, and behavior. Enumerated here are the strengths of various testing methods and the requisites for legally defensible testing. The challenge remains to determine blood ethanol levels in such a manner that the results are scientifically valid and legally defensible. PMID- 1744010 TI - Osteopathic interns' attitudes toward their education and training. AB - The attitudes of two groups of osteopathic medical interns toward their education are compared. The two groups, referred to as osteopathic ideologists and allopathic ideologists, were selected on the basis of their reported first choice of medical school and internship. The groups differed significantly concerning preparation for and commitment to an osteopathic medical career; adherence to osteopathic tenets; evaluation of quality of education; plans for future training; and career plans. Both groups, however, reported a lack of coherence and integration of osteopathic medical principles and practices in their education. Implications for osteopathic medicine and osteopathic medical education are discussed. PMID- 1744011 TI - Incomplete rectal obstruction secondary to adenocarcinoma of the prostate. AB - Ureteral and bladder outlet obstruction are well-known sequelae of adenocarcinoma of the prostate. Contiguous extension of prostate cancer locally to involve the rectum is an uncommon phenomenon. It has been suggested that this is because Denonvillier's fascia is an effective barrier to posterior extension of malignant prostatic neoplasms. Herein, we report a case of this unusual association as well as a review of the literature. PMID- 1744012 TI - Red eyes and red rash with fever: an uncommon initial presentation for staphylococcal obturator abscess with adjacent ischial osteomyelitis. AB - "Red eyes and red rash with fever" is a common pediatric complaint; however, it is an uncommon initial presentation for staphylococcal obturator abscess with adjacent ischial osteomyelitis. The case of a 13-year-old boy who was admitted to the hospital with conjunctivitis, erythematous maculopapular lesions, and fever and had this final diagnosis is reported. The differential diagnosis included various bacterial diseases, several viral illnesses, and rickettsial disease. PMID- 1744013 TI - Axillary disruption of axillobifemoral graft. AB - Axillary disruption of axillobifemoral grafts has not previously been reported after appropriate placement of the graft medially on the axillary artery and proper subpectoral tunneling. Six weeks after undergoing such surgery followed by a relatively uncomplicated postoperative course, the patient--an 81-year-old man- was found unconscious at home. He was resuscitated, and taken to an emergency room where he had a respiratory arrest. At surgery, it was found that the polytetrafluoroethylene graft had separated from the axillary artery. Inspection of the axillary artery showed a completely intact suture line on the artery itself. Graft cultures tested negative. The authors believe the anastomotic disruption was the result of trauma to the anastomosis during cardiopulmonary resuscitation and external cardiac massage. PMID- 1744014 TI - How analytic is psychoanalytic psychotherapy? AB - This essay attempts to resolve some of the ambiguities regarding the differentiation of psychoanalytic psychotherapy from psychoanalysis. It argues that they result from a failure to recognize that psychotherapy, although it is grounded in psychoanalytic knowledge, is fundamentally different from psychoanalysis in that it does not have as its goal an uncovering of the unconscious and therefore does not use the psychoanalytic method devised for this purpose. Psychotherapy, in this view, is understood as a reality-oriented process that helps a person understand the present in continuity with a consciously accessible past and that promotes the integration of divergent but alternatively conscious aspects of the self and the object. The conceptual framework for psychotherapy thus understood is to be found in developmental psychology, object relations theory, and the psychology of the self. The essentially analytic aspects of such a process reside in the psychoanalytic knowledge of human development that guides our understanding of the clinical material but also the limits of our therapeutic endeavors; in the analytic attitude of openness to the accessible and individual meaning of a patient's communications that guards against imposing cognitively deduced interpretations of supposedly unconscious meanings; and in the engagement of, and respect for, the patient's observing ego. PMID- 1744015 TI - The nuclear bomb: a concretization and erotization of power. AB - This article contends that the nuclear bomb is the concrete representation of an archaic idealizing system. It uses concepts published by Atwood and Stolorow (1984) to demonstrate how the bomb is no protection at all to our national defense; rather it compensates for empty or poorly developed psychological structure and function of individual and group. The continued proliferation of the bomb--some 70,000 at last count--despite the knowledge that just a few can obliterate our world is testimonial to the need for a concrete and visible mound of weapons. Since this need can never be satisfied by these means, there can never be enough bombs to be sufficient. The article extends the concept of this faulty or absent development of psychological structure to the weakening or loss of primary affiliative bonding between individuals and groups, which has psychohistorical roots. Three historical developments intertwine and reinforce one another: (1) the isolation of national defense to weapons and war; (2) the evolution of a modern science based on a duality between body (affects) and mind (cognition) and contributing to sexual polarization, in which masculinity has been identified with valued objectivity and femininity has been identified with devalued affiliative affects; (3) the equation of sex and aggression with power and their use as substitutes for derailed development of affiliative needs and functions. PMID- 1744016 TI - Somatization: a perspective from self psychology. AB - Somatization is a complex phenomenon that occurs in many forms and diverse settings. It is not necessarily pathological and may be found in a variety of psychiatric disorders. Much of the psychiatric literature has focused on patients with conversion disorders and hypochondriasis. Psychoanalytic theories regarding such conditions were largely based upon concepts of drive, conflict, and defense. The perspective from self psychology, with its emphasis on subjective experience and the sense of self, may further enhance the psychoanalytic understanding of somatization. Individuals with disturbances in the stability and organization of the self may present with somatic symptoms and disturbances in emotional awareness. Somatization in such cases may be the experiential manifestation of a disturbance in the cohesion of the self and/or may result from defensive operations to ward off affect. The latter may be prominent when affective arousal triggers the psychological threat of fragmentation. Somatization may diminish in such individuals when a self-object relationship is formed that bolsters and consolidates the sense of self. The integration of affect into ongoing subjective experience may also be an important aspect of psychoanalytic treatment in such patients. PMID- 1744017 TI - Child sexual abuse: origins, dynamics, and treatment. AB - This article is intended as an overview of the current literature on child sexual abuse. There are some patterns of psychopathology seen in both the abused and the abusers that warrant further scrutiny. The presence of narcissistic pathology in both groups is interesting, particularly in light of the generationality of child sexual abuse. This finding raises the issue of the nature of psychic injury incurred by some of the victims and places it at the level of early self development. PMID- 1744018 TI - Is psychoanalytic theory relevant to the psychology of women? AB - This article reviews the literature addressing the relevance of psychoanalytic theory to the psychology of women and offers a possible rapprochement between these divergent perspectives. This rapprochement is accomplished first by defining "psychoanalytic theory" and "the psychology of women" in line with current scholarship, then by comparing and contrasting these definitions in an item-by-item analysis. The basic tenets of modern psychoanalytic theory emerge as highly relevant to the understanding of the psychology of women, despite the fact that particular "brands" of psychoanalytic theory may not demonstrate this same compatibility. PMID- 1744019 TI - Adaptation to developmental transformations during the various phases of motherhood. AB - The developmental processes that surround pregnancy and motherhood exert powerful and all-encompassing effects on the lives of the women undergoing such changes. Research has recently determined that the physiological and emotional transformations that occur in pregnant women may have a significant impact on the relationship that gradually develops between mothers and their infants. The growth of this relationship with the infant is directly related to the developmental challenges confronting the expectant women and new mother. Although many women are fearful or ambivalent about expressing their emotions during such periods of developmental change because of the implications of such feelings, exploratory work that encourages the disclosure of dreams and fantasies often enables the therapist to predict the patient's future ability to cope with the challenges of motherhood. This article examines five cases in which the developmental transformations experienced by the woman during the antenatal and postnatal periods significantly influenced the evolution of an attachment relationship with the infant. PMID- 1744020 TI - Somatic correspondences during psychoanalysis. AB - Somatic as well as cognitive correspondences occur during psychoanalytic treatment. The somatic type have received little, if any, attention from the analytic community, at least in terms of published references. Somatic symptom(s), activated by external events in his or her life, first appear in the analyst. Almost immediately thereafter identical or closely similar experiences appear in the analysand and (during the treatment hour) are verbalized by him or her. Should attempts to understand correspondences stop at this point, it is easy to conclude they are due to mere coincidence, but they have deep, unconscious roots. Analytic exploration of these roots reveals practically simultaneous occurrence of certain activated conflict residues in the analyst and comparable ongoing but far less worked-through conflict areas in the analysand. The brief interval when these activated facets become approximate in intensity appears to be the trigger for the correspondence. Preoedipal aspects of unconscious conflict are more apt to be reflected in somatic correspondence, whereas oedipal aspects are more likely to be expressed in cognitive correspondence. In any event, data available from the case material reported suggest that from a psychological point of view the unconscious plays a significant role in extrasensory and unverbalized communication and suggest addition of the concept of body-language transference to that of thought transference. PMID- 1744021 TI - Princess Marie Bonaparte, Edgar Allan Poe, and psychobiography. AB - Princess Marie Bonaparte was a colorful yet mysterious member of Freud's inner circle of psychoanalysis. In analysis with Freud beginning in 1925 (she was then 45 years old), she became a lay analyst and writer of many papers and books. Her most ambitious task was a 700-page psychobiography of Edgar Allan Poe that was first published in French in 1933. She was fascinated by Poe's gothic stories- with the return to life of dead persons and the eerie, unexpected turns of events. Her fascination with Poe can be traced to the similarity of their early traumatic life experiences. Bonaparte had lost her mother a month after her birth. Poe's father deserted the family when Edgar was two years old, and his mother died of tuberculosis when he was three. Poe's stories helped him to accommodate to these early traumatic losses. Bonaparte vicariously shared in Poe's loss and the fantasies of the return of the deceased parent in his stories. She was sensitive and empathetic to Poe's inner world because her inner world was similar. The result of this psychological fit between Poe and Bonaparte was her psychobiography, The Life and Works of Edgar Allan Poe. It was a milestone in psychobiography but limited in its psychological scope by its strong emphasis on early childhood trauma. Nevertheless it proved Bonaparte a bona fide creative psychoanalyst and not a dilettante propped up by her friendship with Freud. PMID- 1744022 TI - Creative brainstorms: a story of madness and genius. PMID- 1744023 TI - Defense and coping in the antinomy between self-maintenance and adaptation. AB - After definitions of the terms defense and coping, the disturbances of both linked to narcissistic personality disorders, borderline personality disorders, and major depressions are described. All three are characterized by deficient narcissism. In narcissistic personality disorders, defense and coping are hindered mainly because of a lack of narcissistic investment of the ego, in borderline personality disorders preponderantly because of a fragmentation-prone ego with its rigid defenses, and in major depressions primarily because narcissistic emptiness or depletion breaks down interest of the ego to get along with the environment or leads to an extreme overinvestment of the remaining narcissism in the objects. Finally, the three levels of object relations--the narcissistic--fusionary one, the level of active ego performances, and the level of free decisions--and their functioning with respect to coping in the three disorders mentioned are discussed. PMID- 1744024 TI - Childhood asthma: a developmental and biopsychosocial model for treatment. PMID- 1744025 TI - Childhood asthma in interaction with family, school, and peer systems: a developmental model for primary care. AB - The developmental/biopsychosocial approach to primary care of childhood asthma offered in the above model emphasizes four interlocking features: 1. Consideration of the biologic, psychologic, and social aspects of asthma which interact with one another and influence disease management and psychosocial functioning and development of the asthmatic child 2. The importance of balance between disease management and quality of life and developmental needs of the patients and their families 3. Appreciation and facilitation of a developmentally synchronized shift toward self care of the asthma and its social and emotional aspects; 4. Central role played by the primary care provider (or health care team) in integrating developmental/biopsychosocial aspects of comprehensive treatment for childhood asthma. PMID- 1744026 TI - Food-induced asthma in China: an analysis in 40 cases. AB - Forty patients with a history of recurrent attacks of asthma after ingesting certain foods are described. All of these individuals had positive intracutaneous skin tests to at least one of the food allergens which was suggested by their history to cause an attack. In four of these patients, a bronchoprovocational challenge was performed with an aerosolized extract of the potential offending food. Clinical manifestations, possible mechanisms, and diagnostic measures for food-induced asthma are discussed. PMID- 1744027 TI - Effect of oral administration of a prostacyclin analog (OP-41483) on pulmonary function and bronchial responsiveness in stable asthmatic subjects. AB - To examine whether prostacyclin has an attenuating effect on nonspecific bronchial responsiveness in asthma, we measured provocative concentration of methacholine producing a 20% fall in forced expiratory volume in 1 second (PC20 FEV1) before and after oral administration of a chemically stable prostacyclin analog (OP-41483) (200 micrograms 4 times a day for 4 days) in 8 patients with stable asthma. Neither baseline pulmonary function nor PC20-FEV1 significantly improved after the treatment. These results suggest that prostacyclin may have no direct effect on bronchial responsiveness in asthmatics. Further studies using more potent and long-lasting prostacyclin mimetic will be needed to confirm the conclusion. PMID- 1744028 TI - Asthma in pregnancy. PMID- 1744029 TI - Effect of yoga training on exercise tolerance in adolescents with childhood asthma. AB - Forty six young asthmatics with a history of childhood asthma were admitted for yoga training. Effects of training on resting pulmonary functions, exercise capacity, and exercise-induced bronchial lability index were measured. Yoga training resulted in a significant increase in pulmonary function and exercise capacity. A follow-up study spanning two years showed a good response with reduced symptom score and drug requirements in these subjects. It is concluded that yoga training is beneficial for young asthmatics. PMID- 1744030 TI - Acute respiratory distress due to vocal cord dysfunction in cystic fibrosis. PMID- 1744031 TI - Disappearance of allergic reaction to cromolyn (cromoglycate) by avoidance and then reintroduction. PMID- 1744032 TI - The product of the Rhizobium meliloti ilvC gene is required for isoleucine and valine synthesis and nodulation of alfalfa. AB - Tn5-induced mutants of Rhizobium meliloti that require the amino acids isoleucine and valine for growth on minimal medium were studied. In one mutant, 1028, the defect is associated with an inability to induce nodules on alfalfa. The Tn5 mutation in 1028 is located in a chromosomal 5.5-kb EcoRI fragment. Complementation analysis with cloned DNA indicated that 2.0 kb of DNA from the 5.5-kb EcoRI fragment restored the wild-type phenotype in the Ilv- Nod- mutant. This region was further characterized by DNA sequence analysis and was shown to contain a coding sequence homologous to those for Escherichia coli IlvC and Saccharomyces cerevisiae Ilv5. Genes ilvC and ilv5 code for the enzyme acetohydroxy acid isomeroreductase (isomeroreductase), the second enzyme in the parallel pathways for the biosynthesis of isoleucine and valine. Enzymatic assays confirmed that strain 1028 was a mutant defective in isomeroreductase activity. In addition, it was shown that the ilvC genes of Rhizobium meliloti and E. coli are functionally equivalent. We demonstrated that in ilvC mutant 1028 the common nodulation genes nodABC are not activated by the inducer luteolin. E. coli ilvC complemented both defective properties (Ilv- and Nod-) found in mutant 1028. These findings demonstrate that R. meliloti requires an active isomeroreductase enzyme for successful nodulation of alfalfa. PMID- 1744033 TI - Mapping, sequence, and apparent lack of function of araJ, a gene of the Escherichia coli arabinose regulon. AB - We report the mapping, sequencing, and study of the physiological role of the fourth arabinose-inducible operon from Escherichia coli, araJ. It is located at 9 min on the chromosome and codes for a single 42-kDa protein that shows no significant homology to other known proteins. Destruction of the chromosomal araJ gene does not detectably affect either of the two arabinose transport systems, the ability of cells to grow on arabinose, or the induction kinetics of the araBAD operon, and thus the physiological role of AraJ, if any, remains unknown. We have also found a long open reading frame upstream of araJ. The sequence of this upstream open reading frame was found to be identical to the previously reported sequence of the sbcC gene (I. S. Naom, S. J. Morton, D. R. F. Leach, and R. G. Lloyd, Nucleic Acids Res. 17:8033-8044, 1989). The carboxyl region of SbcC has an amino acid sequence consistent with this region of SbcC forming an extended alpha-helical coiled-coil. PMID- 1744034 TI - Substitution of active-site His-223 in Pseudomonas aeruginosa elastase and expression of the mutated lasB alleles in Escherichia coli show evidence for autoproteolytic processing of proelastase. AB - The neutral metalloprotease elastase is one of the major proteins secreted into the culture medium by many Pseudomonas aeruginosa strains. Encoded by the lasB gene, the 33-kDa elastase is initially synthesized as a 53-kDa preproenzyme which is processed to the mature form via a 51-kDa proelastase intermediate. To facilitate studies on proteolytic processing of elastase precursors and on secretion, we developed systems for overexpression of lasB in Escherichia coli under the control of the inducible T7 and tac promoters. Although the 51-kDa proelastase form was detectable in E. coli under inducible conditions, most of the elastase produced under these conditions was found in an enzymatically active 33-kDa form. The amino-terminal sequence of the first 15 amino acid residues of this 33-kDa elastase species was identical to that of the mature P. aeruginosa enzyme, suggesting that processing was autocatalytic. To test this possibility, the codon in lasB encoding His-223, a presumed active-site residue, was changed to encode Asp-223 (lasB1) and Tyr-223 (lasB2). The effects of these mutations on enzyme activity and processing were examined. No proteolytic or elastolytic activities were detected in extracts of E. coli cells containing the lasB mutant alleles. Overexpression of the mutated lasB genes in E. coli resulted in the accumulation of the corresponding 51-kDa proelastase species. These were processed in vitro to the respective 33-kDa forms by incubation with exogenous purified elastase, without an increase in proteolytic activity. Molecular modeling studies suggest that the mutations have little or no effect on the conformation of the mutant elastases. In addition, wild-type elastase and the mutant proelastases were localized to the periplasm of E. coli. The present results confirm that His-223 is essential for elastase activity and provide evidence for autoproteolytic processing of proelastase. PMID- 1744035 TI - 13C nuclear magnetic resonance and gas chromatography-mass spectrometry studies of carbon metabolism in the actinomycin D producer Streptomyces parvulus by use of 13C-labeled precursors. AB - Fructose and glutamate metabolism was monitored in cell suspensions of streptomyces parvulus by 13C nuclear magnetic resonance. The experiments were performed for cells grown with various 13C sources in a growth medium containing D-[U-13C]fructose, L-[13C]glutamate, or L-[U-13C]aspartate and with nonlabeled precursors to compare intracellular pools in S. parvulus cells at different periods of the cell life cycle. The transport of fructose into the cells was biphasic in nature; during rapid transport, mannitol, fructose, and glucose 6 phosphate were accumulated intracellularly, whereas during the passive diffusion of fructose, the intracellular carbohydrate pool comprised mainly trehalose (1,1' alpha-alpha-D-glucose). The regulation of fructokinase activity by the intracellular intermediates may play an important role in fructose catabolism in S. parvulus. Transaldolase activity in S. parvulus was determined from the 13C nuclear magnetic resonance labeling pattern of trehalose carbons obtained from cells grown in medium containing either L-[U-13C]aspartate or L-[U-13C]glutamate. Only carbons 4, 5, and 6 of the disaccharide were labeled. Isotopomer analysis of the trehalose carbons led us to conclude that the flux through the reverse glycolytic pathway, condensation of glyceraldehyde 3-phosphate with dihydroxyacetone phosphate, makes at best a minor contribution to the 13C-labeled glucose units observed in trehalose. The pentose pathway and transaldolase activity can explain the labeling pattern of 4,5,6-13C3 of trehalose. Moreover, the transfer of the 13C label of L-[U-13C]aspartate into the different isotopomers of trehalose C4, C5, and C6 by the transaldolase activity allowed us to calculate the relative fluxes from oxaloacetate via gluconeogenesis and through the tricarboxylic acid cycle. The ratio of the two fluxes is approximately 1. However, the main carbon source for trehalose synthesis in S. parvulus is fructose and not glutamate or aspartate. The 13C enrichment and isotopomer population, measured by nuclear magnetic resonance and gas chromatography-mass spectrometry, of the actinomycin D peptide ring enabled us to specify the origins of the five amino acids of actinomycin D. Threonine and proline exhibited isotopomer populations similar to that of the extracellular L [13C]glutamate, indicating that protein catabolism is the origin of their 13C label, whereas the isotopomer populations of sarcosine and N-methylvaline were similar to those of the new intracellular pool of S. parvulus that originated from D-[U-13C]fructose during the production of actinomycin D. PMID- 1744036 TI - Extracellular fibrils and contact-mediated cell interactions in Myxococcus xanthus. AB - Contact-mediated cell-cell interactions play an important role in the social life style of Myxococcus xanthus. Previous investigations have demonstrated that fimbriae (also referred to as pili) and extracellular fibrils are involved in these social interactions (L. J. Shimkets, Microbiol. Rev. 54:473-501, 1990). We have used the relatively new technique of low-voltage scanning electron microscopy (an ultra-high-resolution scanning technique that allows for the nanometer resolution of biological materials) to observe the topological details of cell-cell interactions in M. xanthus. Our observations indicated that the fibrils (which measure approximately 30 nm in diameter) are produced most extensively by cells that are in close contact with each other and are aberrantly produced by the cohesion-deficient dsp mutants. Immunogold analysis identified an antigen which is located exclusively on the extracellular fibrils. Western blots (immunoblots) of this antigen (designated FA-1 for fibrillar antigen 1) indicated that it is composed of several immunoreactive bands (molecular size range, 90 to 14 kDa), all of which are sensitive to protease digestion. A technique for fibril isolation was developed by using FA-1 as a fibril-specific marker. Low-voltage scanning electron microscope observations of swarming cells demonstrated that the expression of fibrils is differentially regulated between adventurous (individual) and socially (group) motile cells. The differential expression of fibrils suggests the existence of a mechanism for the regulation of fibril biosynthesis that functions within the overall system governing social interactions in M. xanthus. PMID- 1744037 TI - Synthesis and fractionation properties of SpoIIGA, a protein essential for pro sigma E processing in Bacillus subtilis. AB - sigma E, a major sporulation-specific sigma factor of Bacillus subtilis, is derived from an inactive precursor protein (pro-sigma E). The formation of sigma E from pro-sigma E requires the products of several stage II genes, including spoIIGA, a gene that is cotranscribed with the pro-sigma E coding region (spoIIGB, or sigE). SpoIIGA has been hypothesized to be both a membrane-bound protein and the protease which converts pro-sigma E into sigma E. to learn more of its properties, we joined the Escherichia coli lacZ gene to the 3' end of spoIIGA as a translational fusion, creating a gene whose product was found to contain both beta-galactosidase and SpoIIGA activities. Assaying for the beta galactosidase activity of the chimeric protein as a measure of its abundance, we determined that the spoIIGA::lacZ product accumulated to approximately 10% the level of a spoIIGB::lacZ fusion protein. Using differential centrifugation to fractionate B. subtilis extracts that contained beta-galactosidase fusion proteins, we observed that the beta-galactosidase activity of the spoIIGA::lacZ fusion protein was preferentially associated with a Triton X-100-sensitive, fast sedimenting portion of the extract, while the beta-galactosidase activity of the spoIIGB::lacZ fusion protein remained primarily in the supernatant fraction. If the properties of the fusion proteins are assumed to be representative of those of the products of the genes to which lacZ is joined, these results support the hypothesis that SpoIIGA is a membrane-bound protein that acts catalytically in the processing of pro-sigma E into sigma E. PMID- 1744038 TI - Genetic evidence for interaction of sigma E with the spoIIID promoter in Bacillus subtilis. AB - During sporulation in Bacillus subtilis, new RNA polymerase sigma factors are produced. These sigma factors direct the transcription of genes that are required for this cellular differentiation. In order to determine the role of each sigma factor in this process, it is necessary to know which promoters are recognized by each sigma factor. The spoIIID gene product plays an important role in the establishment of mother cell-specific gene expression during sporulation. We found that substitution of an alanine at position 124 of the sporulation-specific sigma factor sigma E suppressed the effect of a single-base-pair transition at position -13 of the spoIIID promoter. This alanine substitution in sigma E did not suppress the effect of a transversion at position -12 of the spoIIID promoter. The allele specificity of the interaction between sigma E and the spoIIID promoter is strong evidence that sigma E directs transcription from the spoIIID promoter during sporulation. Position 124 in sigma E is located within a region that is highly conserved among the regions in other sigma factors that probably interact with the -10 regions of their cognate promoters. PMID- 1744039 TI - Molecular analysis of Bacillus subtilis ada mutants deficient in the adaptive response to simple alkylating agents. AB - Previously, we isolated and characterized six Bacillus subtilis ada mutants that were hypersensitive to methylnitroso compounds and deficient in the adaptive response to alkylation. Cloning of the DNA complementing the defects revealed the presence of an ada operon consisting of two tandem and partially overlapping genes, adaA and adaB. The two genes encoded proteins with methylphosphotriester DNA methyltransferase and O6-methylguanine-DNA methyltransferase activities, respectively. To locate the six mutations, the ada operon was divided into five overlapping regions of about 350 bp. The fragments of each region were amplified by polymerase chain reaction and analyzed by gel electrophoresis to detect single strand conformation polymorphism. Nucleotide sequences of the fragments exhibiting mobility shifts were determined. Three of the mutants carried sequence alterations in the adaA gene: the adaA1 and adaA2 mutants had a one-base deletion and insertion, respectively, and the adaA5 mutant had a substitution of two consecutive bases causing changes of two amino acid residues next to the presumptive alkyl-accepting Cys-85 residue. Three mutants carried sequence alterations in the adaB gene: the adaB3 mutant contained a rearrangement, the adaB6 mutant contained a base substitution causing a change of the presumptive alkyl-accepting Cys-141 to Tyr, and the adaB4 mutant contained a base substitution changing Leu-167 to Pro. The adaB mutants produced ada transcripts upon treatment with low doses of alkylating agents, whereas the adaA mutant did not. We conclude that the AdaA protein functions as the transcriptional activator of this operon, while the AdaB protein specializes in repair of alkylated residues in DNA. PMID- 1744040 TI - A gene cluster required for coordinated biosynthesis of lipopolysaccharide and extracellular polysaccharide also affects virulence of Pseudomonas solanacearum. AB - Bacterial cell surface components can be important determinants of virulence. At least three gene clusters important for extracellular polysaccharide (EPS) biosynthesis have been previously identified in the plant pathogen Pseudomonas solanacearum. We have found that one of these gene clusters, named ops, is also required for lipopolysaccharide (LPS) biosynthesis. Mutations in any complementation unit of this cluster decreased EPS production, prevented the binding of an LPS-specific phage, and altered the mobility of purified LPS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, restoration of LPS biosynthesis alone was not sufficient to restore virulence to the wild type level, suggesting that EPS is important for pathogenesis. PMID- 1744041 TI - Cloning and nucleotide sequencing of a novel 7 beta-(4 carboxybutanamido)cephalosporanic acid acylase gene of Bacillus laterosporus and its expression in Escherichia coli and Bacillus subtilis. AB - A strain of Bacillus species which produced an enzyme named glutaryl 7-ACA acylase which converts 7 beta-(4-carboxybutanamido)cephalosporanic acid (glutaryl 7-ACA) to 7-amino cephalosporanic acid (7-ACA) was isolated from soil. The gene for the glutaryl 7-ACA acylase was cloned with pHSG298 in Escherichia coli JM109, and the nucleotide sequence was determined by the M13 dideoxy chain termination method. The DNA sequence revealed only one large open reading frame composed of 1,902 bp corresponding to 634 amino acid residues. The deduced amino acid sequence contained a potential signal sequence in its amino-terminal region. Expression of the gene for glutaryl 7-ACA acylase was performed in both E. coli and Bacillus subtilis. The enzyme preparations purified from either recombinant strain of E. coli or B. subtilis were shown to be identical with each other as regards the profile of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were composed of a single peptide with the molecular size of 70 kDa. Determination of the amino-terminal sequence of the two enzyme preparations revealed that both amino-terminal sequences (the first nine amino acids) were identical and completely coincided with residues 28 to 36 of the open reading frame. Extracellular excretion of the enzyme was observed in a recombinant strain of B. subtilis. PMID- 1744042 TI - Genetic method to identify regulons controlled by nonessential elements: isolation of a gene dependent on alternate transcription factor sigma B of Bacillus subtilis. AB - We describe a general, in vivo method for identifying Bacillus subtilis genes controlled by specific, nonessential regulatory factors. We establish the use of this approach by identifying, isolating, and characterizing a gene dependent on sigma B, an alternate transcription factor which is found early in stationary phase but which is not essential for sporulation. The method relies on two features: (i) a plate transformation technique to introduce a null mutation into the regulatory gene of interest and (ii) random transcriptional fusions to a reporter gene to monitor gene expression in the presence and absence of a functional regulatory product. We applied this genetic approach to isolate genes comprising the sigma B regulon. We screened a random Tn917lacZ library for fusions that required an intact sigma B structural gene (sigB) for greatest expression, converting the library strains from wild-type sigB+ to sigB delta::cat directly on plates selective for chloramphenicol resistance. We isolated one such fusion, csbA::Tn917lacZ (csb for controlled by sigma B), which mapped between hisA and degSU on the B. subtilis chromosome. We cloned the region surrounding the insertion, identified the csbA reading frame containing the transposon, and found that this frame encoded a predicted 76-residue product which was extremely hydrophobic and highly basic. Primer extension and promoter activity experiments identified a sigma B-dependent promoter 83 bp upstream of the csbA coding sequence. A weaker, tandem, sigma A-like promoter was likewise identified 28 bp upstream of csbA. The csbA fusion was maximally expressed during early stationary phase in cells grown in Luria broth containing 5% glucose and 0.2% glutamine. This timing of expression and medium dependence were very similar to those for ctc, the only other recognized gene dependent on sigma B. PMID- 1744043 TI - Effect of chromosome location of Bacillus subtilis forespore genes on their spo gene dependence and transcription by E sigma F: identification of features of good E sigma F-dependent promoters. AB - Translational lacZ fusions to forespore genes of Bacillus subtilis were not expressed in spoIIAC (sigma F) or spoIIIE mutants when the lacZ fusions were integrated at the loci of the same genes or at the SP beta locus. However, some of these genes, including gerA, gpr, spoIIIG (sigma G), and sspE, were expressed in spoIIIE mutants and spoIIIE spoIIIG double mutants (but not in spoIIAC mutants) when the lacZ fusions were integrated at the amyE locus. When tested, the beta-galactosidase made in these mutants was found only in the forespore, and the 5' ends of the mRNAs produced in these mutants were identical to those in a Spo+ background. Analysis of the in vitro transcription of forespore genes by RNA polymerase containing sigma F (E sigma F) revealed a direct correlation between good in vitro transcription by E sigma F and expression at the amyE locus in spoIIIE mutants. This result suggests that forespore genes are transcribed by E sigma F in spoIIIE and spoIIIE spoIIIG mutants. Comparison of the promoter regions of genes transcribed well and poorly by E sigma F in vivo and in vitro showed that good transcription by E sigma F was correlated with G residues at positions -15 and -16, a purine residue at position -13, and a T residue at position -7 relative to the start site of transcription. The importance of these residues in sigma F recognition was confirmed by analysis of the E sigma F dependent transcription in vivo and in vitro of mutant ssp genes. PMID- 1744044 TI - Analysis of the lsi region involved in lipooligosaccharide biosynthesis in Neisseria gonorrhoeae. AB - The genetic locus (lsi-1) responsible for the transformation of the lipooligosaccharide (LOS)-defective Neisseria gonorrhoeae mutant FA5100 to LOS expression was studied by deletion mutagenesis and sequence analysis. An open reading frame that was preceded by a leader sequence containing regions with the potential to form hairpin loops was identified. A perfect sigma 70 promoter consensus sequence was found upstream from this open reading frame. Promoter function was screened for functionality by using lac fusion cassettes and in vitro transcription-translation analysis. A frameshift mutation in the lsi-1 gene was constructed by site-directed mutagenesis and introduced into the chromosome of FA19, the LOS-expressing isogenic parent strain of FA5100. The mutant was characterized by Southern blotting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting (immunoblotting) and found to be phenotypically identical to FA5100. PMID- 1744045 TI - Control of Escherichia coli lysyl-tRNA synthetase expression by anaerobiosis. AB - Escherichia coli lysyl-tRNA synthetase was previously shown to occur as two distinct species encoded by either the lysS or the lysU gene. The expression of one of these genes, lysU, is under the control of cell growth conditions. To study the regulation of lysU, delta lysS strains were constructed. During aerobic growth at 37 degrees C or below, the amount of the lysU product in the cell is so reduced that delta lysS bacteria grow only poorly. The reduced expression of lysU is not related to the steady-state lysyl-tRNA synthetase concentration in the cell, since the expression of a lysU::lacZ fusion is insensitive to the absence of either lysS or lysU or to the addition of a multi-copy plasmid carrying either lysU or lysS. During anaerobic growth in rich medium, the lysU gene becomes strongly expressed and, in cell extracts, the amount of lysyl-tRNA synthetase activity originating from lysU may become seven times greater than the activity originating from lysS. In minimal medium, lysU expression is only slightly induced. Evidence that the sensitivity of lysU expression to anaerobiosis, as well as to low external pH conditions (E. W. Hickey and I. N. Hirshfield, Appl. Environ. Microbiol. 56:1038-1045, 1990), is governed at the level of transcription is provided. PMID- 1744046 TI - The major carotenoid pigment of a psychrotrophic Micrococcus roseus strain: purification, structure, and interaction with synthetic membranes. AB - The major carotenoid pigment of a psychrotrophic Micrococcus roseus strain was purified to homogeneity from methanol extracts of dried cells by reverse-phase liquid chromatography and was designated P-3. On the basis of the UV-visible, infrared, mass, and 1H nuclear magnetic resonance spectra of P-3, it was identified as bisdehydro-beta-carotene-2-carboxylic acid. The pigment interacted with synthetic membranes of phosphatidylcholine and dimyristoyl phosphatidylcholine and stabilized the membranes. These results also indicate that P-3 is different from canthaxanthin, the major carotenoid pigment from a mesophilic M. roseus strain. PMID- 1744047 TI - Trehalose synthesis genes are controlled by the putative sigma factor encoded by rpoS and are involved in stationary-phase thermotolerance in Escherichia coli. AB - The rpoS (katF) gene of Escherichia coli encodes a putative sigma factor (sigma S) required for the expression of a variety of stationary phase-induced genes, for the development of stationary-phase stress resistance, and for long-term starvation survival (R. Lange and R. Hengge-Aronis, Mol. Microbiol. 5:49-59, 1991). Here we show that the genes otsA, otsB, treA, and osmB, previously known to be osmotically regulated, are also induced during transition into stationary phase in a sigma S-dependent manner. otsA and otsB, which encode trehalose-6 phosphate synthase and trehalose-6-phosphate phosphatase, respectively, are involved in sigma S-dependent stationary-phase thermotolerance. Neither sigma S nor trehalose, however, is required for the development of adaptive thermotolerance in growing cells, which might be controlled by sigma E. PMID- 1744048 TI - Characterization of the haloacid dehalogenase from Xanthobacter autotrophicus GJ10 and sequencing of the dhlB gene. AB - The haloacid dehalogenase of the 1,2-dichloroethane-utilizing bacterium Xanthobacter autotrophicus GJ10 was purified from a mutant with an eightfold increase in expression of the enzyme. The mutant was obtained by selecting for enhanced resistance to monobromoacetate. The enzyme was purified through (NH4)2SO4 fractionation, DEAE-cellulose chromatography, and hydroxylapatite chromatography. The molecular mass of the protein was 28 kDa as determined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 36 kDa as determined with gel filtration on Superose 12 fast protein liquid chromatography. The enzyme was active with 2-halogenated carboxylic acids and converted only the L-isomer of 2-chloropropionic acid with inversion of configuration to produce D lactate. The activity of the enzyme was not readily influenced by thiol reagents. The gene encoding the haloacid dehalogenase (dhlB) was cloned and could be allocated to a 6.5-kb EcoRI-BglII fragment. Part of this fragment was sequenced, and the dhlB open reading frame was identified by comparison with the N-terminal amino acid sequence of the protein. The gene was found to encode a protein of 27,433 Da that showed considerable homology (60.5 and 61.0% similarity) with the two other haloacid dehalogenases sequenced to date but not with the haloalkane dehalogenase from X. autotrophicus GJ10. PMID- 1744049 TI - The bacteriocin lactococcin A specifically increases permeability of lactococcal cytoplasmic membranes in a voltage-independent, protein-mediated manner. AB - Lactococcin A is a bacteriocin produced by Lactococcus lactis. Its structural gene has recently been cloned and sequenced (M. J. van Belkum, B. J. Hayema, R. E. Jeeninga, J. Kok, and G. Venema, Appl. Environ. Microbiol. 57:492-498, 1991). Purified lactococcin A increased the permeability of the cytoplasmic membrane of L. lactis and dissipated the membrane potential. A significantly higher concentration of lactococcin A was needed to dissipate the membrane potential in an immune strain of L. lactis. Lactococcin A at low concentrations (0.029 microgram/mg of protein) inhibited secondary and phosphate-bond driven transport of amino acids in sensitive cells and caused efflux of preaccumulated amino acids. Accumulation of amino acids by immune cells was not affected by this concentration of lactococcin A. Lactococcin A also inhibited proton motive force driven leucine uptake and leucine counterflow in membrane vesicles of the sensitive strain but not in membrane vesicles of the immune strain. These observations indicate that lactococcin A makes the membrane permeable for leucine in the presence or absence of a proton motive force and that the immunity factor(s) is membrane linked. Membrane vesicles of Clostridium acetobutylicum, Bacillus subtilis, and Escherichia coli were not affected by lactococcin A, nor were liposomes derived from phospholipids of L. lactis. These results indicate that lactococcin A acts on the cytoplasmic membrane and is very specific towards lactococci. The combined results obtained with cells, vesicles, and liposomes suggest that the specificity of lactococcin A may be mediated by a receptor protein associated with the cytoplasmic membrane. PMID- 1744050 TI - Cloning, characterization, and expression of the spoVB gene of Bacillus subtilis. AB - Mutation of the spoVB gene in Bacillus subtilis causes the production of spores containing a defective cortex and unable to acquire heat resistance. The spoVB locus is highly linked to another spo locus, spoIIIF, characterized by a single mutation (I. L. Lamont and J. Mandelstam, J. Gen. Microbiol. 130:1253-1261, 1984). A 18-kb DNA region overlapping the spoIIIF-spoVB region was cloned in successive steps starting from a Tn917 insertion in the nic locus. The exact location of the spoIIIF and spoVB loci was defined with various integrative plasmids carrying subfragments of that region. DNA sequencing established that spoIIIF and spoVB are a single monocistronic locus encoding a 518-amino-acid polypeptide with features of an integral membrane protein. The precise location of the spoIIIF590 and spoVB91 mutations in that unique open reading frame was determined, and both mutations were sequenced. A null mutation was engineered in the spoIIIF-spoVB locus and led to a typical spoVB phenotype, identical to the phenotype created by either spoIIIF590 or spoVB91, suggesting that the original spoIIIF mutant contained a secondary mutation arresting sporulation at an earlier stage. A transcriptional spoVB-lacZ fusion was constructed, and its expression was found to be directly dependent on RNA polymerase containing sigma E. A null mutation of spoVB had no effect on expression of sspB and cotA, members of the sigma G- and sigma K-controlled regulons respectively, while expression of cotC, a member of the latest known mother cell regulon, was delayed and strongly reduced. These results are consistent with SpoVB being involved in cortex biosynthesis and affecting only indirectly expression of late sporulation genes. PMID- 1744051 TI - Cloning and sequencing of the gene for a Pseudomonas paucimobilis enzyme that cleaves beta-aryl ether. AB - We isolated Pseudomonas paucimobilis SYK-6, which was able to degrade various dimeric lignin compounds (Y. Katayama, S. Nishikawa, M. Nakamura, K. Yano, M. Yamasaki, N. Morohoshi, and T. Haraguchi, Mokuzai Gakkaishi 33:77-79, 1987). This metabolic process is a distinct characteristic of this bacterium, which is equipped with an enzymatic modification system for various dimeric lignin compounds involved in the tricarboxylic acid cycle. Cleavage of the beta-aryl ether linkage is essential in this process, because this linkage is the most abundant (approximately 50%) in lignin. Here, we report the isolation and characterization of the beta-etherase gene, which contains an open reading frame of 843 bp and which we call ligE. This gene was expressed in Escherichia coli, and the enzyme had the same kinetic properties as the P. paucimobilis SYK-6 enzyme. PMID- 1744052 TI - Characterization of endoglucanase A from Clostridium cellulolyticum. AB - A construction was carried out to obtain a high level of expression in Escherichia coli of the gene celCCA, coding for the endoglucanase A from Clostridium cellulolyticum (EGCCA). The enzyme was purified in two forms with different molecular weights, 51,000 and 44,000. The smaller protein was probably the result of proteolysis, although great care was taken to prevent this process from occurring. Evidence was found for the loss of the conserved reiterated domains which are characteristic of C. thermocellum and C. cellulolyticum cellulases. The two forms were extensively studied, and it was demonstrated that although they had the same pH and temperature optima, they differed in their catalytic properties. The truncated protein gave the more efficient catalytic parameters on carboxymethyl cellulose and showed improved endoglucanase characteristics, whereas the intact enzyme showed truer cellulase characteristics. The possible role of clostridial reiterated domains in the hydrolytic activity toward crystalline cellulose is discussed. PMID- 1744053 TI - Characterization of PDC6, a third structural gene for pyruvate decarboxylase in Saccharomyces cerevisiae. AB - Pyruvate decarboxylase is the key enzyme in alcoholic fermentation in yeast. Two structural genes, PDC1 and PDC5 have been characterized. Deletion of either of these genes has little or no effect on the specific pyruvate decarboxylase activity, but enzyme activity is undetectable in mutants lacking both PDC1 and PDC5 (S. Hohmann and H. Cederberg, Eur. J. Biochem. 188:615-621, 1990). Here I describe PDC6, a gene structurally closely related to PDC1 and PDC5. The product of PDC6 does not seem to be required for wild-type pyruvate decarboxylase activity in glucose medium; delta pdc6 mutants have no reduced specific enzyme activity, and the PDC6 deletion did not change the phenotype or the specific enzyme activity of mutants lacking either or both of the other two structural genes. However, in cells grown in ethanol medium the PDC6 deletion caused a reduction of pyruvate decarboxylase activity. Northern (RNA) blot analysis showed that PDC6 is weakly expressed, and expression seemed to be higher during growth in ethanol medium. This behavior remained obscure since pyruvate decarboxylase catalyzes an irreversible reaction. Characterization of all combinations of PDC structural gene deletion mutants, which produce different amounts of pyruvate decarboxylase activity, showed that the enzyme is also needed for normal growth in galactose and ethanol medium and in particular for proper growth initiation of spores germinating on ethanol medium. PMID- 1744054 TI - Cell cycle parameters of Escherichia coli K-12. AB - A computer simulation routine was used to calculate the DNA distributions of exponentially growing cultures of Escherichia coli K-12. Simulated distributions were compared with distributions obtained experimentally by flow cytometry. Durations of the DNA replication period (C) and the postreplication period (D) were found by minimizing the difference between theoretical and experimental DNA histograms. It was demonstrated that the K-12 strains AB1157 and CM735 had C and D periods that differed widely from each other and from those of the previously measured strain B/rA, while strain MC1000 was shown to have the same durations of the C and D periods as strain B/rA. The variation between K-12 strains may explain the divergence in the literature regarding their C and D periods. Strains W3110 and AB1157 recA1 had DNA histograms that could not be adequately simulated by the classical Cooper-Helmstetter model, which is consistent with the asymmetrically located origin and terminus for W3110 and the asynchrony of initiation for AB1157 recA1. PMID- 1744055 TI - Characterization of the heat shock response in Mycobacterium bovis BCG. AB - We have for the first time characterized the heat shock response in mycobacteria both at the level of transcription, by RNA extraction, Northern (RNA) blotting, and hybridization with gene-specific probes for the Mycobacterium tuberculosis 65 and 71-kDa heat shock proteins (HSPs), and at the level of translation, by [35S]methionine labelling, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography. We observed increased synthesis of 40-, 65 , 71-, and 90-kDa proteins, which appear to be major HSPs in mycobacteria. The 40 , 71-, and 90-kDa HSPs are coordinately regulated in terms of temperature requirements and kinetics of induction but differ in the levels of expression. The 65- and 71-kDa HSPs are differentially regulated in response to temperature, with different kinetics and levels of induction. mRNA transcript sizes for the 71 , 65-, 40-, and 30-kDa proteins were found to be broadly consistent with DNA sequence open reading frames. A maximum increase of about 69-fold in the levels of mRNA for the 71-kDa HSP after 45 min of heat shock at 45 degrees C was observed, whereas the 65-kDa HSP mRNA increased only 5-fold. It was also found that in M. bovis BCG, as in Escherichia coli, a major control mechanism of the heat shock response is operative at the level of transcription. An ability to characterize the heat shock response in mycobacteria provides an experimental model with which to study environmentally regulated gene expression and an opportunity to identify virulence genes, which may coregulate as part of the heat shock regulon. PMID- 1744056 TI - Release of a cell surface protein during development of Myxococcus xanthus. AB - VGP is a major cell-surface glycoprotein present in vegetative cells of Myxococcus xanthus. Serological assays indicated that this protein was released from cells and accumulated in the medium during development, i.e., aggregation, fruiting body formation, and myxosporulation. Cells induced to form spores in the absence of aggregation retained VGP, indicating that loss of VGP was associated with developmental aggregation rather than myxosporulation. Anti-VGP antibodies inhibited vegetative cell gliding, suggesting the protein may also be required for motility. PMID- 1744057 TI - Specificity of SOS mutagenesis in native M13lacI phage. AB - Base substitutions account for 90% of all forward mutations sequenced in unmodified M13lacI DNA grown in both UV-irradiated and nonirradiated hosts. The principal effect of SOS induction was an increase in the contribution of transversions, in particular A.T----T.A events. PMID- 1744058 TI - Regulation of laccase biosynthesis in the plant-pathogenic fungus Cryphonectria parasitica by double-stranded RNA. AB - Transmissible hypovirulence of the chestnut blight fungus, Cryphonectria parasitica, is associated with cytoplasmic double-stranded-RNA (dsRNA) viruses. The fungal laccase has attracted interest because its activity is reduced in hypovirulent dsRNA-containing strains. A laccase cDNA clone was isolated by screening a cDNA expression library with antibodies against the purified extracellular laccase. The amino acid sequence deduced from part of the cDNA clone revealed high homology to other fungal laccases, especially to the Neurospora crassa laccase. A major laccase transcript 2.3 kb in length was detected in Northern (RNA) blots. In liquid culture, extracellular laccase activity was reduced by about 75% in the hypovirulent (dsRNA-free) strain EP155/2. In contrast, production of biomass was not affected by the dsRNA. Northern blot analysis indicated that dsRNA down regulates laccase biosynthesis by reducing laccase mRNA accumulation. The laccase gene is one of several developmentally regulated genes affected by the presence of dsRNA. PMID- 1744059 TI - Localization of outer surface proteins A and B in both the outer membrane and intracellular compartments of Borrelia burgdorferi. AB - Borrelia burgdorferi B31 with and without outer membranes contained nearly identical amounts of outer surface proteins A and B. The majority of each immunogen also was localized intracellularly by immunocryoultramicrotomy. These results are inconsistent with the widely held belief that outer surface proteins A and B are exclusively outer membrane proteins. PMID- 1744060 TI - Regulation of the adhE gene, which encodes ethanol dehydrogenase in Escherichia coli. AB - The respiratory control of adhE, which encodes ethanol (alcohol) dehydrogenase in Escherichia coli, was examined at the transcriptional level by using various phi (adhE'-lacZ) adhE+ merodiploid strains. Expression of the adhE'-lacZ operon fusion was increased about eightfold by anaerobic growth. Under anaerobic growth conditions, provision of nitrate lowered the level of expression. Nitrate repression was more severe than aerobic repression. From analyses of various mutants with mutations related to nitrate reduction, nitrate repression appears to result from two effects. (i) When nitrate was present, NarL, the positive regulator of the nar operon, exerted a direct repression on adhE expression, which was demonstrable even aerobically. (ii) The chemical reduction of nitrate exerted an indirect effect by altering the cellular redox potential. PMID- 1744061 TI - A 102-center prospective study of seizure in association with bupropion. AB - BACKGROUND: This trial was conducted to determine the incidence of seizures associated with the use of bupropion. METHOD: A total of 3341 depressed patients from 102 sites were enrolled in this 8-week, prospective, open trial. Following the 8-week treatment phase, patients could elect to enroll in a humanitarian continuation phase of unlimited duration. Dosing was initiated at 225 mg/day and increased to 450 mg/day as tolerated. Investigators carefully monitored seizure occurrences and rated their patients' response to and tolerance of bupropion. RESULTS: A total of 1986 patients (61%) completed the 8-week treatment phase, and 1616 (81%) of these elected to be maintained on bupropion treatment in the humanitarian continuation phase. The observed seizure rate was 0.24% for the treatment phase and 0.40% for the entire study. An 8-week survival analysis performed on patients with a dosing regimen of 300 to 450 mg/day yielded a cumulative rate of 0.36%. Patients, including those previously resistant to antidepressant treatment, responded to and tolerated bupropion well. CONCLUSION: These rates confirm earlier seizure estimates and fall within accepted parameters for antidepressant drugs. This trial enhances bupropion's position as a valuable alternative for the management of depression. PMID- 1744062 TI - Hypochondriasis and obsessive compulsive disorder: overlaps in diagnosis and treatment. AB - BACKGROUND: Hypochondriasis is a disorder for which there are no established effective treatments. Hypochondriacs, in their obsessions about illness, compulsions to check with others, and failure to be reassured, share many features in common with those who have obsessive compulsive disorder (OCD). METHOD: The authors present a case series of six patients with DSM-III-R hypochondriasis, five of whom also had a history of OCD. Two of the six agreed to be treated with doses of fluoxetine typically used to treat OCD. RESULTS: Both patients, one of whom had no past history of OCD, showed a marked improvement in hypochondriacal symptoms. CONCLUSION: These findings suggest that a subgroup of patients with hypochondriasis may be particularly responsive to serotonin reuptake blockers. PMID- 1744063 TI - Painful ejaculation associated with antidepressants in four patients. AB - BACKGROUND: Painful ejaculation associated with tricyclic antidepressants is rarely reported in the medical literature. METHOD: Painful ejaculation following the administration of imipramine and clomipramine is described in four patients. RESULTS: The phenomenon occurred in all patients during the first 3 weeks of treatment and disappeared within several days when the tricyclic dosage was reduced or the medication was withdrawn. CONCLUSION: Painful ejaculation was apparently evoked by tricyclic antidepressant administration. Clinicians should be aware of this underreported side effect. PMID- 1744064 TI - An open trial of fluoxetine in patients with anorexia nervosa. AB - BACKGROUND: Anorexia nervosa is a disorder of unknown etiology with a high rate of relapse and no known treatment. Because anorexia nervosa shares some similarities with obsessive compulsive disorder, we hypothesized that a serotonin specific medication might be useful in the treatment of this illness. METHOD: We administered an open trial of fluoxetine to 31 patients with DSM-III-R anorexia nervosa. Most anorexics were started on fluoxetine treatment after inpatient weight restoration and then discharged from the hospital and followed up as outpatients. RESULTS: At the time of follow-up (11 +/- 6 months on fluoxetine), 29 of the 31 patients had maintained their weight at or above 85% average body weight (97% +/- 13% average body weight for the group). We judged response as good in 10, partial in 17, and poor in 4 anorexics as measured by improvements in eating behavior, mood, and obsessional symptoms. Restrictor anorexics responded significantly better than bulimic and/or purging-type anorexics. CONCLUSION: This open trial suggests that fluoxetine may help patients with anorexia nervosa maintain a healthy body weight as outpatients. The reasons for the positive effects of fluoxetine are uncertain, but the agent may help by improving eating behavior and/or reducing obsessionality, depression, and anxiety. It is important to emphasize that this was not a double-blind, placebo-controlled study. Thus we can not be certain of the efficacy of fluoxetine and caution that fluoxetine should not be used as the sole treatment of anorexia nervosa at this time. PMID- 1744065 TI - Carbamazepine for treatment-resistant melancholia. AB - BACKGROUND: There have only been a few studies of the role of carbamazepine in the management of treatment-resistant depression. METHOD: The response to carbamazepine of 16 melancholic patients, who had been depressed for an extended period despite a number of standard treatments, was studied retrospectively. RESULTS: Seven patients (44%) had a moderate or marked improvement. The responders included both psychotic and nonpsychotic depressives, and patients with concurrent organic brain disease. There was, however, a high rate of complications, with 5 of these 7 responders (71%) having to discontinue carbamazepine because of adverse effects. This high rate of complications may have reflected the older age of our sample. CONCLUSION: These findings suggest the efficacy of carbamazepine in melancholic patients who have not responded to conventional treatments, but indicate that the high rate of significant side effects may limit its long-term usefulness. PMID- 1744066 TI - Fluoxetine-induced bradycardia. PMID- 1744067 TI - Personality disorder diagnosis in old age. PMID- 1744068 TI - Clomipramine treatment of trichotillomania. PMID- 1744069 TI - Does fluoxetine induce suicidality? PMID- 1744070 TI - Environmental influences on the onset of winter depression. PMID- 1744071 TI - von Willebrand factor. PMID- 1744072 TI - Marker exchange of the structural genes for nitric oxide reductase blocks the denitrification pathway of Pseudomonas stutzeri at nitric oxide. AB - Bacterial denitrification reverses nitrogen fixation in the global N-cycle by transforming nitrate or nitrite to dinitrogen. Both nitrite and nitric oxide (NO) are considered as the chemical species within the denitrification pathway, that precede nitrous oxide (N2O), the first recognized intermediate with N,N-bonds antecedent to N2. Molecular cloning of the structural genes for NO reductase from Pseudomonas stutzeri has allowed us to generate the first mutants defective in NO utilization (Nor- phenotype) by marker exchange of the norCB genes with a gene cassette for gentamicin resistance. Nitric oxide reductase was found to be an indispensable component for denitrification; its loss constituted a conditionally lethal mutation. NO as the sole product accumulated from nitrite by mutant cells induced for nitrite respiration (denitrification). The Nor- mutant lost the capability to reduce NO and did not grow anymore anaerobically on nitrate. A Nir Nor- double mutation, that inactivated also the respiratory nitrite reductase cytochrome cd1 rendered the bacterium again viable under anaerobiosis. Our observations provide evidence for a denitrification pathway in vivo of NO2(-)--- NO----N2O, and N,N-bond formation catalyzed by NO reductase and not by cytochrome cd1. PMID- 1744073 TI - Ribosome-independent GTPase activity of translation initiation factor IF2 and of its G-domain. AB - In the absence of ribosomes, Bacillus stearothermophilus translation initiation factor IF2 (Mr = 82 kDa) and its GTP-binding domain (i.e. the G-domain, Mr = 41 kDa) promote barely detectable hydrolysis of GTP. Upon addition of some aliphatic alcohols, however, the rate of nucleotide cleavage is substantially increased with both IF2 and G-domain, the highest stimulation being observed with 20% (v/v) ethanol. Under these conditions, the rates of ribosome-independent GTP hydrolysis with both IF2 and G-domain are approximately 30-fold lower than the corresponding rates obtained in the presence of ribosomes, while the Km for GTP is approximately the same in all cases. These results indicate that, as with the other two prokaryotic G proteins involved in translation (i.e. elongation factors EF-Tu and EF-G), also in the case of IF2, the GTPase catalytic center resides in the factor and, more specifically, in its G-domain. PMID- 1744074 TI - A synthetic peptide mimic of plasma apolipoprotein E that binds the LDL receptor. AB - Human plasma apolipoprotein E (apoE) is a low density lipoprotein (LDL) receptor ligand. It targets cholesterol-rich lipoproteins to LDL receptors on both hepatic and peripheral cells. The region of apoE responsible for its binding to the LDL receptor has been localized to amino acids 140-160. An apoE 141-155 monomeric peptide and a dimeric 141-155 tandem peptide were synthesized and tested for their inhibition of 125I-LDL degradation by human fibroblasts and human monocytic like cells, THP-1. The monomer had no activity at 250 microM, but the dimer inhibited 125I-LDL degradation by 50% at 5 microM. The inhibition was specific for the LDL receptor because the dimer did not inhibit the degradation of 125I acetylated LDL by scavenger receptors expressed by phorbol ester-stimulated THP-1 cells. As reported for native apoE, amino acid substitutions of Lys-143----Ala, Leu-144----Pro, and Arg-150----Ala decreased the inhibitory effectiveness of the dimer. Furthermore, a trimer of the 141-155 sequence had a 20-fold greater inhibitory activity than the dimer. Studies with a radioiodinated dimer indicated that some of the inhibitory activity could be a result of the interaction of the dimer with LDL. However, direct binding of the 125I-dimeric peptide to THP-1 cells was observed as well. This binding was time-dependent, linear with increasing cell number, Ca(2+)- but not Mg(2+)-dependent, saturable, inhibited by lipoproteins, and increased by preculture of the cells in lipoprotein-depleted medium. Therefore, a synthetically prepared dimeric repeat of amino acid residues 141-155 of apoE binds the LDL receptor. PMID- 1744075 TI - Structure of oligosaccharides on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris. AB - Saccharomyces SUC2 invertase, secreted by the methylotrophic yeast Pichia pastoris and purified to homogeneity from the growth medium by DE-52 chromatography, appeared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a diffuse ladder of species at 85-90 kDa, while the secreted Saccharomyces form migrated as a broad band from 100 to 150 kDa. Endo-beta-N acetylglucosaminidase H released the Pichia invertase carbohydrate generating a 60-kDa protein with residual Asn-linked GlcNAcs and oligosaccharides separated on Bio-Gel P-4 into Man8-11GlcNAc. Nearly 75% of the oligosaccharides were equally distributed between Man8,9GlcNAc, while 17% were Man10GlcNAc and 8% were Man11GlcNAc. Oligosaccharide pools were analyzed for homogeneity by high-pH anion exchange chromatography, and structures were assigned using 500 MHz one- and two dimensional 1H NMR spectroscopy. Pichia Man8GlcNAc was the same isomer as found in Saccharomyces, which arises by removing the alpha 1,2-linked terminal mannose from the middle arm of the lipid-oligosaccharide Man9GlcNAc (Byrd, J. C., Tarentino, A. L., Maley, F., Atkinson, P. H., and Trimble, R. B. (1982) J. Biol. Chem. 257, 14657-14666). The Man9GlcNAc pool was 5% lipid-oligosaccharide precursor and 95% Man8GlcNAc isomer with a terminal alpha 1,6-linked mannose on the lower-arm alpha 1,3-core-linked residue (Hernandez, L. M., Ballou, L., Alvarado, E., Gillece-Castro, B. L., Burlingame, A. L., and Ballou, C. E. (1989) J. Biol. Chem. 264, 11849-11856). An alpha 1,2-linked mannose on the new alpha 1,6-linked branch in Man9GlcNAc provided 80% of the Man10GlcNAc, which is the structure on Saccharomyces invertase (Trimble, R. B., and Atkinson, P. H. (1986) J. Biol. Chem. 261, 9815-9824). A minor Man10GlcNAc (12%) and the principal Man11GlcNAc (82%) were the major Man9,10GlcNAc with novel alpha 1,2-linked mannoses on the preexisting alpha 1,2-linked termini. Although Pichia glycans did not have terminal alpha 1,3-linked mannoses as found on Saccharomyces core oligosaccharides, over 60% of the structures were isometric configurations unique to lower eukaryotes. PMID- 1744076 TI - Quantitative analysis of molecular species of diacylglycerol and phosphatidate formed upon muscarinic receptor activation of human SK-N-SH neuroblastoma cells. AB - Quantitative changes in the total mass and the molecular species of 1,2-diacyl-sn glycerol (DAG) and phosphatidic acid (PA) formed upon muscarinic receptor activation were studied in cultured human SK-N-SH neuroblastoma cells. DAG was isolated from the total lipid extracts of carbachol (CCh)-stimulated and unstimulated cells and after benzoylation, was subjected to reverse phase high performance liquid chromatography to separate the component species. The molecular species of DAG were identified by analyzing the fatty acid composition of each separated fraction by gas chromatography, and their total and individual masses were quantified from the known amount of an internal standard, 1,2 distearoyl-sn-glycerol, added during the extraction of the lipid. Relatively high basal levels of DAG (1.5 nmol/mg protein) are present in these cells, and addition of CCh elicited a 50-60% increase in the total amounts of DAG within 5 min. The increase was biphasic: an initial major peak at 5 min was followed by a sustained increase that persisted for at least 30 min. An increase in DAG was elicited by both full and partial muscarinic agonists and was blocked by atropine. The presence of extracellular Ca2+ was necessary for muscarinic receptor-activated formation of DAG. To determine the source of the DAG, the molecular species of the major phospholipids present in SK-N-SH cells were also analyzed. The phospholipids were first enzymatically hydrolyzed to DAGs which were then analyzed as described above. A number of unusual fatty acids, the major one being 20:3 (n-9), were present in these lipids especially in the phosphoinositides and also in the DAG formed after CCh stimulation. Within 5 s of CCh stimulation there were transient increases in the DAG species representative of phosphoinositides. By 5 min the newly formed molecular species of DAG resembled a mixture of phosphoinositides and phosphatidylcholine (PC). Quantitative comparison of the molecular species compositions of phosphoinositides, PC, and newly formed DAGs indicated that at time periods up to 10 min, approximately 30% of the DAG originated from the phosphoinositides and the rest from PC. At longer intervals (greater than 20 min), most (85%) of DAGs originated from PC. Activation of muscarinic receptors in SK-N-SH cells also elicited an increase in PA (200% in 5 min). A quantitative molecular species analysis, using 1,2-distearoyl-sn-glycerol-3-P as internal standard, was performed by enzymatic (alkaline phosphatase) hydrolysis of PA to DAG and subsequent analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744077 TI - Identification of the pheophytin-QA-Fe domain of the reducing side of the photosystem II as the Cu(II)-inhibitory binding site. AB - Oxygen evolution by photosystem II membranes was inhibited by Cu(II) when 2,6 dichlorobenzoquinone or ferricyanide, but not silicomolybdate, was used as electron acceptor. This indicated that Cu(II) affected the reducing side of the photosystem II. The inhibition curves of Cu(II), o-phenanthroline and 3-(3,4 dichlorophenyl)-1,1-dimethylurea (DCMU), were compared; the inhibitory patterns of Cu(II) and o-phenanthroline were very similar and different in turn from that of DCMU. Cu(II) did not eliminate or modify the electron paramagnetic resonance signal at g = 8.1 ascribed to the non-heme iron of the photosystem II reaction center, indicating that the inhibition by Cu(II) was not the result of the replacement of the iron by Cu(II). Controlled trypsin digestion of thylakoid membranes inhibited oxygen evolution using 2,6-dichlorobenzoquinone, but had no effect when using ferricyanide or silicomolybdate. Using ferricyanide, oxygen evolution of trypsin-treated thylakoids was insensitive to DCMU but became even more sensitive to Cu(II) and o-phenanthroline than nontreated thylakoids; however, trypsinized thylakoids were insensitive to inhibitors in the presence of silicomolybdate. We conclude that Cu(II) impaired the photosystem II electron transfer before the QB niche, most probably at the pheophytin-QA-Fe domain. PMID- 1744078 TI - Activation of the proteinase B precursor of the yeast Saccharomyces cerevisiae by autocatalysis and by an internal sequence. AB - Proteinase B (PrB) is a subtilisin-like serine protease found in the vacuole of the yeast Saccharomyces cerevisiae. It is first made as a large precursor that consists of a putative signal sequence, a 260-amino acid pro region, the serine protease domain, and two small COOH-terminal post regions (Moehle, C. M., Dixon, C. K., and Jones, E. W. (1989) J. Cell Biol. 108, 309-324). This precursor is glycosylated and proteolytically processed at least three times before mature enzyme is formed. To determine whether an intact PrB catalytic site is required for proteolytic processing of the precursor, point mutations were generated at the codons for the active site serine or aspartate residues by site-directed mutagenesis. The effect of these mutations on PrB processing suggests that the large pro region may be cleaved by an intramolecular, autocatalytic mechanism. The properties of a prb1 mutant that accumulates a 37-kDa precursor in addition to mature sized mutant PrB antigen suggests that the final proteolytic cleavage step is also autocatalytic. A prb1 deletion that lacks codons for the large pro region was made to test whether this part of the precursor is required for formation of mature PrB. Analysis of this mutant revealed two functions for this region: it prevents N-linked glycosylation of the serine protease domain and it allows the PrB precursor to be processed by proteinase A. The pro region can fulfill this latter function if added as a separate molecule, so long as glycosylation of the catalytic domain is prevented by other means. PMID- 1744079 TI - Transforming growth factor-beta 1 inhibits scavenger receptor activity in THP-1 human macrophages. AB - The macrophage scavenger receptor, a 220-kDa trimeric membrane glycoprotein, mediates the internalization of modified forms of low density lipoprotein (LDL) such as acetyl-LDL and oxidized-LDL and thus is likely to play a key role in atheroma macrophage foam cell formation. In addition, recent evidence suggests that the scavenger receptor may be an important macrophage binding site for lipopolysaccharide involved in lipopolysaccharide scavenging by macrophages. However, little is known about the regulation of this important receptor. We now report that the induction of scavenger receptor activity (as measured by acetyl LDL stimulation of intracellular cholesterol esterification) seen in phorbol ester-differentiated THP-1 human macrophages was completely suppressed to the level seen in undifferentiated THP-1 monocytes by picomolar concentrations of transforming growth factor-beta 1 (TGF-beta 1). 125I-Acetyl-LDL degradation was inhibited in a dose-dependent manner by TGF-beta 1, with maximal inhibition (approximately 70%) occurring at 24 pM TGF-beta 1. Scatchard analysis revealed that TGF-beta 1 treatment resulted in a approximately 2-fold decrease in receptor number, and Northern blot analysis of RNA isolated from differentiated THP-1 macrophages demonstrated approximately 2-fold less scavenger receptor mRNA in TGF beta 1-treated cells compared with that in macrophages not treated with TGF-beta 1. Since TGF-beta 1 is thought to be present in both atherosclerotic and inflammatory lesions, the above findings may have physiological relevance regarding the regulation of atheroma foam cell formation and/or the regulation of lipopolysaccharide clearance by macrophages. PMID- 1744080 TI - Mechanism of fluoride activation of G protein-gated muscarinic atrial K+ channels. AB - Aluminum fluoride (AlF4-) activates the heterotrimeric G protein Gs (stimulatory G protein of adenylylcyclase) (Sternweis, P. C., and Gilman, A. G. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 4888-4891) and GT (transducin), and for GT, Bigay et al. (Bigay, J., Deterre, P., Pfister, C., and Chabre, M. (1985) FEBS Lett. 191, 181-185) have made the intriguing proposal that AlF4- acts by mimicking the gamma-phosphate of GTP. The endogenous G protein (probably G alpha i-2 or G alpha i-3 (Yatani, A., Mattera, R., Codina, J., Graf, R., Okabe, K., Padrell, E., Iyengar, R., Brown, A. M., and Birnbaumer, L. (1988) Nature 336, 680-682) that stimulates the muscarinic atrial K+ (K+[ACh]) channel is also thought to be activated by AlF4- (Kurachi, Y., Nakajima, T., and Ito, H. (1987) Circulation 76, 105P). To investigate the AlF4- mechanism, we applied potassium fluoride (KF) to the cytoplasmic face of inside-out membrane patches excised from guinea pig atria. We found that KF activated single K+[ACh] channel currents in both a concentration- and a Mg(2+)-dependent manner. Activation persisted following removal of KF, but unlike activation by guanosine 5'-(3-thiotriphosphate) (GTP gamma S), was fully reversed by removal of Mg2+. Evidence for Al3+ involvement was that the Al3+ chelator deferoxamine (500 microM) inhibited KF activation and that at low concentrations of KF (less than 1 mM), micromolar AlCl3 concentrations potentiated KF stimulation. The rate of activation produced by KF was far slower than the rate produced by GTP or GTP gamma S, and unlike these guanine nucleotides, the rate was unchanged in the presence of agonist. To test the gamma-phosphate-mimicking hypothesis, we evaluated the requirement for GDP; and to accomplish this, it was necessary to establish a condition that ensured exchange of guanine nucleotides. This condition was satisfied by using the muscarinic agonist carbachol because both the rate and the extent of activation of the K+[ACh] channels produced by GTP were much faster in carbachol, and both were greatly slowed when GDP was added along with GTP. By contrast, the effects of KF were unchanged by carbachol in the presence or absence of GDP. Further evidence that GDP is not essential for activation by AlF4- was provided by the observation that during carbachol activation and following extensive washing with GMP, guanosine 5'-O-(2-thiodiphosphate) at blocking concentrations had no effect on activation produced by KF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744081 TI - Identification of novel factors which bind specifically to the core promoter of the immunoglobulin heavy chain gene. AB - Nuclear extracts from HeLa cells and the B-cell line, BJA-B, generated two protein-DNA complexes which bound specifically to sequences in the TATA box of the immunoglobulin heavy chain gene (IgH) promoter. Complex A also bound the core promoter of a retroviral long terminal repeat but did not bind to five other promoters including the adenovirus major late promoter. Of these seven promoters, complex B bound only to the IgH promoter. Footprinting analysis revealed that both complexes A and B bound sequences which include the TATA element, and complex A additionally contacted sequences downstream to +28. Mutation of the IgH TATA element from ATTAATATA to GCTA-TAAAA, the optimal TATA sequence as found in the major late promoter, resulted in a 10-fold decrease in binding to complex A and a 25-fold decrease in binding complex B. Surprisingly, both transfection experiments in HeLa cells and in vitro transcription experiments with whole nuclear extract demonstrated that mutation of the TATA box in the core IgH promoter to this consensus sequence resulted in a 2-fold decrease in the level of transcription. These data suggest that the specific sequence of the TATA region is important, and factors which recognize these sequences, such as complex A and B, may modulate the level of transcription from the IgH promoter. PMID- 1744082 TI - The role of ATP and free ADP in metabolic coupling during fuel-stimulated insulin release from islet beta-cells in the isolated perfused rat pancreas. AB - The isolated perfused rat pancreas was used to test the hypothesis that total cellular ATP or the ratio of ATP/free ADP plays the primary role in coupling intermediary metabolism to the biophysical events that are the basis of glucose stimulated insulin release. The pancreas was preperfused for 20 min with 4.0 mM of a physiological mixture of 20 amino acids plus 4.2 mM glucose, and insulin release was then stimulated for 150 s by suddenly increasing the glucose to 8.3 mM. The pancreas was sampled at 24, 48, 72, and 150 s after the switch. The content of total ATP, ADP, AMP, Pi, phosphocreatine, and creatine were measured in beta-cell enriched cores of pancreatic islets microdissected from freeze-dried pancreas cryostat sections. Metabolites were measured by quantitative histochemical enzymatic cycling techniques. Modeling studies were carried out to assess the impact of biochemical analytical results on the membrane potential of the beta-cells. The level of free ADP was calculated using the creatine kinase equilibrium reaction and an intracellular pH of 7.2. First phase insulin release was stimulated at least 10-fold with the maximum reached 45 s after adding high glucose. The biochemical analytical data demonstrate that the total cellular level of the putative coupling factor ATP and of the ratios ATP/free ADP and ATP/free ADP x Pi are not significantly influenced by a glucose level change that causes a more than 10-fold surge of insulin release. The strength and limitations of the present experimental strategy and the implications of the results for our understanding of metabolic coupling in glucose-stimulated insulin release are discussed. PMID- 1744083 TI - Drosophila laminin A chain sequence, interspecies comparison, and domain structure of a major carboxyl portion. AB - Recent studies ascribed some biological actions of cell adhesion and cell outgrowth to the carboxyl-most 1200 amino acids of vertebrate laminin A chains. Here we report a 6.1-kilobase pair nucleotide cDNA sequence encoding 1951 amino acids and the carboxyl end of a Drosophila laminin A chain. It corresponds to the mouse laminin A domains G, I, II, and III, but may represent a different type of laminin A chain. The arrangement of the cysteine-rich repeats of domain III resembles that of B2 chains. However, it has more amino acid identity with a portion of the mouse laminin A chain domain IIIb than with other laminin repeats. Domains I and II are consistent with an interrupted coiled-coil alpha-helical model of the long arm of laminin but are poorly conserved. The G domain contains five subdomains which are individually related to subdomains of vertebrate laminin A chains. The results indicate that laminin G subdomains should be considered individually, rather than merely as parts of a G-globule. A sequence of hydroxyamino acids contributes to a spacer between two of the subdomains. Stretches of hydroxyamino acids may be indicative of junctions between domains of extracellular Drosophila proteins. PMID- 1744084 TI - Dietary sucrose enhances processing of mRNA-S14 nuclear precursor. AB - The rapid response of rat hepatic mRNA-S14 to hormonal or dietary manipulation makes it an excellent model to study the control of lipogenic enzyme mRNA. The mechanism of regulation of this mRNA by triiodothyronine (T3) or sucrose remains controversial. Although initial studies suggested that T3 stabilized the nuclear precursor, subsequent studies suggest that T3 acts by increasing the transcriptional rate of this gene. More recently, the induction of mRNA-S14 by sucrose administration was shown to be associated with an increase in transcriptional "run-on" activity. Because T3 and carbohydrate feeding synergistically regulate this mRNA, we studied the response to short and long term high carbohydrate feeding in hypothyroid and euthyroid rats. We found the response to the lipogenic diet was rapid in hypothyroid rats, with maximal levels of mRNA-S14 attained by 4 h (2.2 +/- 0.6 chow fed versus 13.5 +/- 2.5 pg/micrograms RNA on lipogenic diet). The rapid induction by the lipogenic diet contrasts with the diminished response to sucrose by gastric gavage (4.6 +/- 1.2 pg/micrograms RNA) over the same time interval. Despite the large increase in the mature mRNA induced by the lipogenic diet, the rise in the nuclear precursor was small and not different from that observed after sucrose gavage (0.14 +/- 0.01 chow, 0.26 +/- 0.03 sucrose gavage, 0.25 +/- 0.04 pg/micrograms RNA lipogenic diet). The molar ratio of the mature to precursor mRNA-S14 showed progressive increases with the smallest level in the fasting rat, an intermediate level in the chow-fed and sucrose gavaged rats, and the highest level in the animals fed a lipogenic diet (2.1, 16.5, 16.3, 62.7, respectively). Based on the previously reported half-life for the mature mRNA-S14, these data show that feeding sucrose by gavage or by a lipogenic diet leads to enhanced fractional conversion of precursor to mature mRNA-S14 with a simultaneous stabilization of the precursor mRNA-S14. PMID- 1744085 TI - Allene oxide and aldehyde biosynthesis in starfish oocytes. AB - Allene oxides are a very unusual type of epoxide that, in biological systems, are formed by the enzymic dehydration of fatty acid hydroperoxides (lipoxygenase products). This reaction occurs widely in plants, in which allene oxide synthesis is a key step in the conversion of linolenic acid to jasmonic acid, the plant growth regulator. We report biosynthesis of the allene oxide (8R)-8,9-epoxyeicosa (5Z,9,11Z,14Z)-tetraenoic acid via the (8R)-lipoxygenase metabolism of arachidonic acid in starfish oocytes. Formation of the allene oxide was deduced from high pressure liquid chromatography, UV, gas chromatography-mass spectrometry and 1H-NMR analyses of the precise structure and mechanism of biosynthesis of its major hydrolysis product, the alpha-ketol 8-hydroxy-9 ketoeicosa-(5Z,11Z,14Z)-trienoic acid. A second enzymic activity detected in the oocytes (hydroperoxide lyase) cleaves specifically the (8R)-hydroperoxy substrate into C7 and C13 fragments, identified as the hydroxyacid, (5Z)-7-hydroxyheptenoic acid, and two aldehydes, (2E,4Z,7Z)-tridecenal and its 4E isomer. Discovery of the allene oxide synthase and hydroperoxide lyase marks the first definitive localization of these enzymic activities to an animal cell. It was established previously that the (8R)-lipoxygenase metabolite (8R)-HETE will activate the maturation (re-initiation of meiosis) of starfish oocytes. The individual 8 lipoxygenase products may be involved at distinct stages of cell development. PMID- 1744086 TI - Quantitation of acyl-CoA and acylcarnitine esters accumulated during abnormal mitochondrial fatty acid oxidation. AB - We have used radio-high pressure liquid chromatography to study the acyl-CoA ester intermediates and the acylcarnitines formed during mitochondrial fatty acid oxidation. During oxidation of [U-14C]hexadecanoate by normal human fibroblast mitochondria, only the saturated acyl-CoA and acylcarnitine esters can be detected, supporting the concept that the acyl-CoA dehydrogenase step is rate limiting in mitochondrial beta-oxidation. Incubations of fibroblast mitochondria from patients with defects of beta-oxidation show an entirely different profile of intermediates. Mitochondria from patients with defects in electron transfer flavoprotein and electron transfer flavoprotein:ubiquinone oxido-reductase are associated with slow flux through beta-oxidation and accumulation of long chain acyl-CoA and acylcarnitine esters. Increased amounts of saturated medium chain acyl-CoA and acylcarnitine esters are detected in the incubations of mitochondria with medium chain acyl-CoA dehydrogenase deficiency, whereas long chain 3 hydroxyacyl-CoA dehydrogenase deficiency is associated with accumulation of long chain 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters. These studies show that the control strength at the site of the defective enzyme has increased. Radio-high pressure liquid chromatography analysis of intermediates of mitochondrial fatty acid oxidation is an important new technique to study the control, organization and defects of the enzymes of beta-oxidation. PMID- 1744087 TI - The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. AB - A heparan sulfate proteoglycan is a component of all basement membranes. This molecule consists of three heparan sulfate side chains linked to a large core protein of approximately 400 kDa. We have isolated seven overlapping murine cDNA clones that encode the entire mRNA sequence of 12.685 kilobases of this molecule. This sequence has a single open reading frame of 3,707 amino acids that encodes for a protein of 396 kDa. Identical or near identical matchups with nine peptide sequences derived from the core protein of the molecule isolated from the Engelbreth-Holm-Swarm tumor were found with the deduced sequence. Sequence analysis and data base comparison of the deduced sequence show the protein to consist of five different domains, most of which contain internal repeats. Domain I contains a start methionine followed by a typical signal transfer sequence and a unique segment of 172 amino acids that contains the three probable sites of heparan sulfate attachment, SGD. Domain II contains four cysteine- and acidic amino acid-rich repeats that are very similar to those found in the LDL receptor and proteins such as GP330. Domain III consists of cysteine-rich and globular regions, both of which show similarity to those in the short arm of the laminin A chain. Domain IV contains 14 repeats of the immunoglobulin superfamily that are most highly similar to the immunoglobulin-like repeats in the neural cell adhesion molecule. Domain V contains three repeats with similarity to the laminin A chain G domain that are separated by epidermal growth factor-like regions not found in the laminin A chain. As the primary structural data agree with the appearance of the molecule in the electron microscope as a series of globules separated by rods, or "beads on a string," we have adopted the name perlecan for this molecule. The variety of domains in perlecan suggest multiple interactions with other molecules. PMID- 1744088 TI - GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. AB - The transcription factors GATA-1, GATA-2, and GATA-3 were found to be expressed in several mouse and rat mast cell lines that contain mast cell carboxypeptidase A (MC-CPA) and other proteases in their cytoplasmic granules. GATA-1 mRNA was not detected in P815 cells, an immature mouse mastocytoma-derived cell line that lacks electron-dense granules and has low levels of secretory granule proteases. Because the 5'-flanking regions of the mouse and human MC-CPA genes contained a conserved GATA-binding motif 51 base pairs upstream of their translation initiation sites, the ability of GATA-binding proteins to regulate the promoter activity of the MC-CPA gene was examined in rat basophilic leukemia cells, mouse P815 cells, and transfected mouse P815 cells that expressed GATA-1. In all three mast cell lines, the promoter activity of the MC-CPA gene depended on the GATA binding site. GATA-1, GATA-2, and GATA-3 are thus the first DNA-binding proteins identified in mast cells which regulate the promoter activity of a gene that encodes a secretory granule protease. PMID- 1744089 TI - ATP-dependent regulation of flagellar adenylylcyclase in gametes of Chlamydomonas reinhardtii. AB - Adenylylcyclase activity in the flagella of gametes of Chlamydomonas reinhardtii was inhibited by prior incubation at or below 30 degrees C in the presence of ATP. This decrease did not occur in the absence of ATP, in the presence of the ATP analog 5'-adenylylimidodiphosphate (App(NH)p), or in the presence of ATP plus the protein kinase inhibitor staurosporine (2 microM). If ATP treatment was performed in the absence of an ATP-regenerating system, activity initially declined and subsequently recovered. Incubation of flagella at 45 degrees C in the absence of ATP or incubation at lower temperatures in the presence of either App(NH)p or staurosporine both increased adenylylcyclase activity (over 10-fold) and blocked subsequent ATP-dependent loss of activity at 30 degrees C. This heat induced activation was prevented by the presence of ATP plus an ATP-regenerating system. Incubation of flagella with [gamma-32P]ATP followed by gel electrophoresis in sodium dodecyl sulfate indicated the presence of endogenous protein kinase and protein phosphatase activities. These data suggest that the flagellar adenylylcyclase in Chlamydomonas gametes is inhibited by phosphorylation and stimulated by dephosphorylation. This mechanism for regulating adenylylcyclase may underlie the rapid increase in cyclic AMP that is induced by flagellar adhesion during fertilization in Chlamydomonas. PMID- 1744090 TI - Conformational requirement for lysine hydroxylation in collagen. Structural studies on synthetic peptide substrates of lysyl hydroxylase. AB - An attempt has been made to understand the conformational determinants that govern the hydroxylation of selected lysyl residues in the nascent collagen molecule by lysyl hydroxylase (EC 1.14.11.4). A series of peptide substrates of the enzyme, ranging in length from 3 to 12 residues, were synthesized. These included: tert-butyloxylcarbonyl (t-Boc)-Ile-Lys-Gly; Boc-Ala-Lys-Gly; N-acetyl Ala-Lys-Gly-Ser; Hyp-Gly-Pro-Lys-Gly-Glu; Leu-Hyp-Gly-Ala-Lys-Gly-Glu; Gly-Phe Hyp-Gly-Leu-Hyp-Gly-Ala-Lys-Gly-Glu; (Hyp-Gly-Pro-Lys-Gly-Glu)2; and Ala-Arg-Gly Ile-Lys-Gly-Ile-Arg-Gly-Phe-Ser-Gly. The conformational features of these peptides were studied by spectroscopic methods so as to relate this information with the kinetic parameters for the interaction of these peptides with purified lysyl hydroxylase. Spectroscopic data, supported by conformational energy calculations, indicated that the tripeptides t-Boc-Ile-Lys-Gly and t-Boc-Ala-Lys Gly adopt a gamma-turn structure in water and trifluoroethanol with Lys in the second position of the turn. In the tetra- and larger peptides two structures, the beta-turn and a polyproline-II (PP-II) type extended conformation, were identified. The proportions of these two structures in a given peptide depended on the polarity of the solvent. All of the peptides were hydroxylated by lysyl hydroxylase isolated from chicken embryos. In contrast, a control peptide, t-Boc Ala-Gly-Lys which adopted a beta-turn with Lys at the end of the turn, was not hydroxylated. Competitive inhibition of the hydroxylation of protocollagen by some of the peptides showed a common binding site for these substrates in the enzyme's active site. Kinetic data on the peptides indicated improved hydroxylation rate (higher Vmax) in peptides having relatively higher beta-turn content and improved binding (lower Km) in peptides with higher content of the PP II structure. The efficacy of the substrate was also governed by its chain length. These data suggest that the conformational criterion for lysine hydroxylation in collagen-related peptides is the presence of a "bent" structure, such as the gamma- or beta-turn at the catalytic site of lysyl hydroxylase and an "extended" PP-II type structure at the binding site(s) of the enzyme's active site. This suggestion also provides a conformational rationale for earlier observations on the substrate specificity of lysyl hydroxylase. PMID- 1744091 TI - Modulation of renal epithelial cell growth by glucosylceramide. Association with protein kinase C, sphingosine, and diacylglycerol. AB - Two independent approaches were employed to explore the potential role of endogenous glucosylceramide or a closely related glucosphingolipid in mediating the cellular proliferation of Madin-Darby canine kidney cells. First, cultured cells were depleted of glucosphingolipids by exposure to a glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. This agent markedly inhibited cell growth and DNA synthesis in a time- and concentration-dependent manner. Second, cells were grown in the presence of conduritol B epoxide, an inhibitor of glucosylceramide beta-D-glucosidase. Exposure of cells to this inhibitor resulted in the time-dependent accumulation of glucosylceramide with a corresponding increase in cellular proliferation. Alterations in protein kinase C activity were evaluated as a potential mechanism for these effects on growth. Both membrane- and cytosol-associated protein kinase C (PKC) activity declined under conditions of glucosylceramide synthase inhibition and increased under conditions of beta-glucosidase inhibition. The changes in PKC activity were evident after DEAE-cellulose purification. Diacylglycerol levels increased in response to both glucosylceramide synthase and beta-glucosidase inhibition. Ceramide and sphingosine levels changed only in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, increasing due to lack of conversion to glucosylceramide. However, the elevation in endogenous sphingosine was probably insufficient to account for the decrease in PKC, considering the high level of diacylglycerol in the cells. These data demonstrate an association between glucosylceramide levels, PKC activity, and cell growth. PMID- 1744092 TI - Regulation of free cytosolic Ca2+ concentration in the outer segments of bovine retinal rods by Na-Ca-K exchange measured with fluo-3. I. Efficiency of transport and interactions between cations. AB - Regulation of free cytosolic Ca2+ concentration in the rod outer segments (ROS) isolated from bovine retinas was examined with the fluorescent Ca(2+)-indicating dye fluo-3. In situ calibration of cytosolic fluo-3 was done in the presence of the Ca2+ ionophore A23187 and yielded a dissociation constant of 500 nM for the Ca(2+)-fluo-3 complex. Ca2+ influx in Ca(2+)-depleted ROS was completely abolished when internal Na+ was removed suggesting that Ca2+ influx exclusively occurred via Na-Ca-K exchange. The most striking observation was that Na-Ca-K exchange could mediate a rapid increase in cytosolic free Ca2+ over the most of the usable indicating range of fluo-3 (from 10 nM to 2 microM), even when exposed to free external Ca2+ concentrations as low as 10 nM. From a comparison between changes in free Ca2+ and changes in total Ca2+, we conclude that physiologically occurring changes in cytosolic free Ca2+ are mediated by exchange fluxes less than 1% of the maximal Na-Ca-K exchange flux. The Na-Ca-K exchanger could mediate both K(+)-dependent and K(+)-independent Ca2+ influx; Li+ caused a complete inhibition of K(+)-independent Ca2+ influx, but had no effect on K(+)-dependent Ca2+ influx. We examined the complex interactions of alkali cations with Ca2+ influx and discuss the results in terms of a three-site model for the Na-Ca-K exchanger (Schnetkamp, P. P. M. and Szerencsei, R. T. (1991) J. Biol. Chem. 266, 189-197). Ca2+ competed with one Mg2+ ion or two Na+ ions for binding to a common site. High K+ concentration greatly diminished the ability of Na+ and Mg2+ to compete with Ca2+ for this common site on the exchanger protein. As a result, high internal K+ induced a conformation of the exchange protein that kinetically favoured Ca2+ extrusion. PMID- 1744093 TI - Regulation of intracellular free Ca2+ concentration in the outer segments of bovine retinal rods by Na-Ca-K exchange measured with fluo-3. II. Thermodynamic competence of transmembrane Na+ and K+ gradients and inactivation of Na(+) dependent Ca2+ extrusion. AB - Regulation of cytosolic free Ca2+ in the physiologically relevant submicromolar range was measured in isolated intact bovine rod outer segments (ROS) with the intracellular Ca(2+)-indicating dye fluo-3. Changes in free Ca2+ were compared with changes in total Ca2+ measured with 45Ca fluxes and a good qualitative correlation was observed. Ca2+ homeostasis in isolated bovine ROS was exclusively mediated via the Na-Ca-K exchanger. Free cytosolic Ca2+ concentration was lowered by an increase in the inward Na+ gradient, was raised by an increase in external K+, and was raised by depolarization of the plasma membrane. The simplest stoichiometry consistent with these qualitative observations is 4Na:(1Ca + 1K). The individual K:Ca, Na:Ca, and K:Na coupling ratios were deduced from quantitative changes in cytosolic free Ca2+ upon changes in the transmembrane Na+ and K+ gradients. The observed changes in free Ca2+ did not agree with changes in free Ca2+ calculated on the basis of the above fixed stoichiometry which may reflect the flexibility in the Ca:K coupling ratio observed before in flux experiments (Schnetkamp, P. P. M., Szerencsei, R. T., and Basu, D. K. (1991) J. Biol. Chem. 266, 198-206). The most dramatic discrepancy was observed for the Na:Ca coupling ratio: the expected very large changes in cytosolic free Ca2+ upon changes in the transmembrane Na+ gradient were not observed. Rapid Na(+)-induced Ca2+ extrusion was unable to lower cytosolic free Ca2+ below 100 nM, even under nonequilibrium conditions and despite the observation that Ca2+ influx via reverse Na-Ca-K exchange readily occurred at a free external Ca2+ concentration of 20 nM. We conclude that the Na(+)-dependent extrusion mode of the Na-Ca-K exchanger occurs in a brief (20-s) burst of high maximal velocity transport followed by a nearly complete inactivation of transport. The importance of our findings for Ca2+ homeostasis in functioning rod photoreceptors is discussed. PMID- 1744094 TI - Disulfide bonding controls the processing of retroviral envelope glycoproteins. AB - The mitogenic membrane glycoprotein (gp55) encoded by Friend erythroleukemia virus is inefficiently processed from the rough endoplasmic reticulum (RER) and only 3-5% reaches plasma membranes. Because this processed component (gp55P) contains larger and more complex oligosaccharides, it can be separated from RER gp55. In nonreducing conditions, gp55P is a unique disulfide-bonded dimer, whereas RER gp55 consists of monomers and dimers with diverse intrachain and interchain disulfide bonds. This suggests that gp55 folds heterogeneously and that only one homodimer is competent for export from the RER. Pulse-chase analyses of gp55 components labeled with radioactive amino acids indicated that formation of diverse disulfide-bonded components occurred within minutes of polypeptide synthesis and that malfolded components did not later isomerize to generate dimers competent for export from the RER. Chemical studies suggested that all 12 cysteines of gp55 were oxidized within 5 min after synthesis of the protein. In contrast, the envelope glycoprotein precursor (gPr90) encoded by a replication-competent murine leukemia virus folds more homogeneously, and it is then processed and cleaved to form an extracellular glycoprotein gp70 plus a transmembrane protein p15E. The fully processed glycoprotein contains an unoxidized cysteine sulfhydryl that isomerizes reversibly with a disulfide bond that links gp70 to p15E. Consequently, only a proportion of gp70 and p15E is disulfide-bonded, and dissociation occurs when the environment becomes even slightly reducing. The gp55 glycoprotein appears to be an extreme example of protein malfolding associated with imprecise and irreversible disulfide bonding. We discuss evidence that folding inefficiencies are common for retroviral proteins that have newly evolving pathogenic functions. PMID- 1744095 TI - Arginine 197 of lac repressor contributes significant energy to inducer binding. Confirmation of homology to periplasmic sugar binding proteins. AB - Based on primary sequence homology between the lactose repressor protein and periplasmic sugar-binding proteins (Muller-Hill, B. (1983) Nature 302, 163-164), a hypothetical sugar-binding site for the lac repressor was proposed using the solved x-ray crystallographic structure of the arabinose-binding protein (ABP) (Sams, C. F., Vyas, N. K., Quiocho, F. A., and Matthews, K. S. (1984) Nature 310, 429-430). By analogy to Arg151 in the ABP sugar site, Arg197 is predicted to play an important role in lac repressor binding to inducer sugars. Hydrogen bonding occurs between Arg151 and the ring oxygen and 4-hydroxyl of the sugar ligand, two backbone carbonyls, and a side chain in ABP, and similar interactions in the lac repressor would be anticipated. To test this hypothesis, Arg197 in the lac repressor protein was altered by oligonucleotide-directed site-specific mutagenesis to substitute Gly, Leu, or Lys. Introduction of these substitutions at position 197 had no effect on operator binding parameters of the isolated mutant proteins, whereas the affinity for inducer was dramatically decreased, consistent with in vivo phenotypic behavior obtained by suppression of nonsense mutations at this site (Kleina, L. G., and Miller, J. H. (1990) J. Mol. Biol. 212, 295-318). Inducer binding affinity was reduced approximately 3 orders of magnitude for Leu, Gly, or Lys substitutions, corresponding to a loss of 50% of the free energy of binding. The pH shift characteristic of wild-type repressor is conserved in these mutants. Circular dichroic spectra demonstrated no significant alterations in secondary structure for these mutants. Thus, the primary effect of substitution for Arg197 is a very significant decrease in the affinity for inducer sugars. Arginine is uniquely able to make the multiple contacts found in the ABP sugar site, and we conclude that this residue plays a similar role in sugar binding for lactose repressor protein. These results provide experimental validation for the proposed homology between ABP and the lac repressor and suggest that homology with ABP may be employed to generate additional insight into the structure and function of this regulatory protein. PMID- 1744096 TI - Mechanism of conversion of human apo- to holomethionine synthase by various forms of cobalamin. AB - Methionine synthase catalyzes the conversion of N5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine. Methylcobalamin (Me-Cbl) is tightly bound to methionine synthase and is required for enzymatic activity. When added to crude tissue homogenates, Me-Cbl stimulates methionine synthase but similar stimulation is observed with hydroxocobalamin, cyanocobalamin (CN-Cbl), and adenosyl-Cbl, although the mechanisms involved are unknown. We prepared human apomethionine synthase and studied its activation in the presence of [14C]CN-Cbl and [14CH3]Me-Cbl with concentrations of 2-mercaptoethanol ranging from 0.15 to 100 mM. We observed that the removal of the labeled upper axial ligands from CN Cbl and Me-Cbl both paralleled the activation of human apomethionine synthase. Spectral studies employing CN-Cbl and Me-Cbl showed that both forms of Cbl must be converted to Cob(II)alamin before they can bind to human apomethionine synthase and convert it to its activated holoenzyme form. Studies with 14 different Cbl analogues with alterations in various portions of the corrin ring and the nucleotide showed that all of the analogues were able to fully activate human methionine synthase when they were reduced with 2-mercaptoethanol. Full activation occurred at lower concentrations of many of the Cbl analogues than occurred with Cbl itself. We conclude that Me-Cbl and other forms of Cob(III)alamin do not bind to human apomethionine synthase and that all must first be reduced to Cob(II)alamin before such binding can occur. The fact that human methionine synthase shows little absolute specificity for alterations in various portions of the Cbl molecule suggests that the potent inhibition of mammalian methionine synthase activity observed in vivo with various Cbl analogues is due to inhibition of intracellular Cbl transport or to inhibition of the enzymatic formation of Cob(II)alamin rather than to direct inhibition of mammalian methionine synthase itself. PMID- 1744097 TI - The effect of carbohydrate on the structure and stability of erythropoietin. AB - Erythropoietin is a glycoprotein hormone that stimulates the maturation of late erythroid progenitor cells. It has three N-linked and one O-linked carbohydrates which play an important role in the biosynthesis and biological activities of the protein. To determine the role the carbohydrate might have in maintaining the conformational stability of the protein, the protein expressed in mammalian cells (fully glycosylated), the asialo mammalian-expressed protein, and the protein expressed in Escherichia coli (no carbohydrate) were compared for their stability to guanidine HCl, pH, and temperature. Circular dichroism was used to follow protein unfolding. Both the intact and asialo mammalian-expressed proteins unfolded with a cooperative transition in guanidine HCl, with a midpoint at 1.75 M guanidine HCl. The E. coli-expressed material unfolded with a midpoint of 1.2 M guanidine HCl, and a delta G of unfolding which was 1.4 kcal/mol less than that of the two glycosylated molecules. The E. coli-derived protein was also significantly less stable to pH-induced conformational changes, showing a cooperative transition in 35% glycerol with a midpoint at pH 4.4, while both the intact and asialo mammalian-expressed molecules had a transition midpoint of pH 3.75 in the absence of glycerol, and approximately pH 3 in the presence of 35% glycerol. The E. coli-expressed molecule unfolded and precipitated upon heating to 44 degrees C, while the asialo and intact mammalian-expressed proteins remained soluble, with a Tm of 56 degrees C. From these experiments, the carbohydrate appears to play a critical role in stabilizing the erythropoietin molecule to denaturing conditions, and this increased stability does not depend on the presence of sialic acid. PMID- 1744098 TI - Molecular cloning and characterization of prolactin-like protein C complementary deoxyribonucleic acid. AB - In this report, we describe the isolation and characterization of a full length cDNA clone for rat prolactin-like protein C (PLP-C) and describe the expression of PLP-C mRNA in the developing rat placenta. Nucleotide sequence analysis of the PLP-C cDNA clone predicted a mature protein of 238 amino acids, including a 30 amino acid signal sequence. The predicted PLP-C amino acid sequence contains seven cysteine residues, three tryptophan residues, and two putative N-linked glycosylation sites. Six of the cysteine residues in PLP-C are located in positions homologous to the cysteines of pituitary prolactin (PRL). Additional sequence similarities with pituitary PRL and other members of the rat placental PRL family are evident. The PLP-C gene was localized to rat chromosome 17. Northern blot analysis showed that the PLP-C cDNA clone specifically hybridized to a 1.0-kilobase mRNA. PLP-C mRNA was first detectable between days 13 and 14 of gestation, peaked by day 18 of gestation, and remained elevated until term. In situ hybridization analysis indicated that PLP-C mRNA was specifically expressed by spongiotrophoblast cells and some trophoblast giant cells in the junctional zone region of rat chorioallantoic placenta. PMID- 1744099 TI - Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains. AB - Hemoglobin (Hb) Chico (Lys beta 66----Thr at E10) has a diminished oxygen affinity (Shih, D. T.-b., Jones, R. T., Shih, M. F.-C., Jones, M. B., Koler, R. D., and Howard, J. (1987) Hemoglobin 11, 453-464). Our studies show that its P50 is about twice that of Hb A and that its cooperativity, anion, and Bohr effects between pH 7 and 8 are normal. The Bohr effect above pH 8 is somewhat reduced, indicating a small but previously undocumented involvement of the ionic bond formed by Lys beta 66 in the alkaline Bohr effect. Since the oxygen affinity of the alpha-hemes is likely to be normal, that of the beta-hemes in the tetramer is likely to be reduced by the equivalent of 1.2 kcal/mol beta-heme in binding energy. Remarkably, both initial and final stages of oxygen binding to Hb Chico are of lowered affinity relative to Hb A under all conditions examined. The isolated beta chains also show diminished oxygen affinity. In T-state Hb A, Lys(E10 beta) forms a salt bridge with one of the heme propionates, but comparison with other hemoglobin variants shows that rupture of this bridge cannot be the cause of the low oxygen affinity. X-ray analysis of the deoxy structure has now shown that Thr beta 66 either donates a hydrogen bond to or accepts one from His beta 63 via a bridging water molecule. This introduces additional steric hindrance to ligand binding to the T-state that results in slower rates of ligand binding. We measured the O2/CO partition coefficient and the kinetics of oxygen dissociation and carbon monoxide binding and found that lowered O2 and CO affinity is also exhibited by the R-state tetramers and the isolated beta chains of Hb Chico. PMID- 1744100 TI - Progesterone-regulated cyclic modulation of membrane metalloendopeptidase (enkephalinase) in human endometrium. AB - Membrane metalloendopeptidase (MMEP; EC 3.4.24.11; enkephalinase) catalyzes the degradation of endothelins, enkephalins, atrial natriuretic factor, substance P, and other small bioactive peptides. We found that MMEP is present in human endometrium, localized primarily in stromal cells of this tissue, and that the specific activity of MMEP (and immunoreactive MMEP protein) in endometrial tissue is correlated in a highly significant positive manner with the concentration of progesterone in plasma. In estrogen-treated, human endometrial stromal cells in monolayer culture, the specific activity of MMEP increases in response to treatment with progestin; and, this increase is accompanied by increases in immunoreactive MMEP protein, newly synthesized MMEP, and MMEP mRNA. PMID- 1744101 TI - Identification of regulatory sequences in the type 1 plasminogen activator inhibitor gene responsive to transforming growth factor beta. AB - Regulation of the human type 1 plasminogen activator inhibitor (PAI-1) promoter by transforming growth factor-beta (TGF beta) was studied. An 800-base pair fragment from the PAI-1 promoter and 5'-flanking region was fused to the firefly luciferase reporter gene and transfected into Hep3B human hepatoma cells. Treatment of the cells with TGF beta induced luciferase activity by more than 50 fold. Transfection studies using constructs with 5' or 3' deletions through this region revealed that two sequences were important in the TGF beta response. The first sequence was located in the proximal promoter (-49 to -87) and mediated an 11-fold induction with TGF beta, while the second more distal region (-636 to 740) contained two sequences which together mediated a 50-fold or greater response. Sequence comparison indicated that both of the responsive regions contained sequences with high homology to the AP-1 consensus binding site. Moreover, gel retardation analysis experiments demonstrated that both sequences bound a common nuclear protein, and that an oligonucleotide containing a consensus AP-1 sequence was able to compete for the binding of this common protein. Thus, the response of the PAI-1 gene to TGF beta is mediated by at least two separate regions, and both of these regions contain DNA sequences homologous to the AP-1 binding site. PMID- 1744102 TI - Isolation and characterization of the human gene for ADP-ribosylation factor 3, a 20-kDa guanine nucleotide-binding protein activator of cholera toxin. AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. Five different human ARFs have been identified by cDNA cloning. Northern analysis using ARF 3-specific oligonucleotides identified two mRNAs of 3.7 and 1.2 kilobases (kb). We report here the complete nucleotide sequence of the 3.7-kb ARF 3 mRNA derived from three overlapping cDNAs isolated from human hippocampus and fetal brain cDNA libraries, as well as the structure of human ARF 3 gene. Sequences of two overlapping genomic clones indicated that the ARF 3 gene spans approximately 18.3 kb and contains five exons and four introns. The conserved amino acid sequences involved in guanine nucleotide binding by ARF 3 are distributed among separate exons, as found in other GTP-binding protein genes. Translation initiates in exon 2 which includes the sequence GXXXXGK that probably participates in phosphate binding and GTP hydrolysis. The sequence DVGG in exon 3 coordinates binding of Mg2+ and the beta-phosphate of GDP. In the ARF 3 gene in contrast to those of other GTP-binding proteins, the sequence NKXD (which is thought to contribute to the specificity of interaction with the guanine ring) is divided between exons 4 and 5. The latter encodes the COOH-terminal 53 amino acids of ARF 3 and contains greater than 2500 base pairs of untranslated DNA. The sequence AATTAA is 19 bases 5' to the polyadenylation addition site of the 3.7-kb mRNA. Multiple transcription start sites were identified by primer extension and S1 and mung bean nuclease analyses. The 5'-flanking region of exon 1 contains neither a TATA nor a CAAT box, but is high in GC content (greater than 70%) and includes three potential Sp1-binding sites (GC box), consistent with the promoters described for several housekeeping genes. The 1.2-kb ARF 3 mRNA is shown to arise by use of an alternative polyadenylation signal (AACAAA) at nucleotide 1091 within the ARF 3 cDNA. PMID- 1744103 TI - Amino acid sequences Gly-Pro-Leu-Tyr and Asn-Pro-Glu-Tyr in the submembranous domain of the insulin receptor are required for normal endocytosis. AB - We have recently shown that the immediately submembranous domain of the human insulin receptor (hIR) is required for rapid ligand-dependent internalization (Thies, R. S., Webster, N. J., and McClain, D. A. (1990) J. Biol. Chem. 265, 10132-10137). This region contains one copy of an NPXY sequence that is required for endocytosis of the low density lipoprotein receptor. In order to dissect and analyze the specific sequences involved in endocytosis of the insulin receptor, we have mutated the NPXY sequence from NPEY (residues 957-960) to APEA (NPEY/APEA). In addition, we have mutated a similar sequence in the same region, changing GPLY (residues 950-953) to APLA (GPLY/APLA). The cDNAs encoding the normal hIR and these mutant receptors were transfected into Rat 1 fibroblasts. The expressed receptors bound insulin with high affinity and retained insulin stimulated tyrosine kinase activity. Despite the ability of these mutant receptors to bind insulin and undergo autophosphorylation, the GPLY/APLA receptor internalized insulin at only 32% of the rate of normal hIR at low receptor occupancy. On the other hand, the NPEY/APEA receptor internalized insulin at 87% of the normal rate. These results were confirmed by measuring internalization of photoaffinity-labeled insulin receptors. Another receptor with both the NPEY/APEA and GPLY/APLA mutations internalized to a lesser degree than the GPLY/APLA receptor and at a rate equivalent to that seen for a receptor with the entire submembranous domain deleted. A receptor with the complete normal submembranous domain but with the tyrosine kinase and C-terminal region of the hIR deleted exhibited only a basal internalization rate. We conclude that the information contained in the GPLY and, to a lesser extent, the NPEY sequences are necessary but not sufficient for signaling internalization of the insulin receptor. PMID- 1744104 TI - Hormonal activation of gene transcription in ras-transformed NIH3T3 cells overexpressing RII alpha and RII beta subunits of the cAMP-dependent protein kinase. AB - ras-Transformed NIH3T3 (R3T3) cells were transfected with expression vectors for the RII alpha and RII beta regulatory subunits of the type II isozyme of cAMP dependent protein kinase, and the effects on gene activation by corticotropin releasing factor (CRF) and prostaglandin E1 (PGE1) were analyzed. In RII alpha and RII beta-overexpressing cells, type II isozyme levels were increased, and type I isozyme levels were eliminated, demonstrating that both RII regulatory subunits compete efficiently with RI for catalytic subunit. The type II isozyme separated into three peaks on high performance liquid chromatography, referred to as A, B, and C. Western blot analysis strongly suggests that peak A and peak C correspond to holoenzymes containing RII beta and RII alpha, respectively. Overexpression of RII alpha resulted in the loss of peak A and a dramatic reduction in RII beta protein with no change in RII beta mRNA, indicating that the level of RII beta protein is controlled posttranscriptionally and that RII beta protein may become unstable when displaced from C. The role of type I and II kinases in transcriptional activation was investigated by comparing the response of control and RII expressing clones to site-selective cAMP analogs and the hormones, CRF and PGE1. The site-selective analogs demonstrated that either type I or type II kinase could activate the cAMP-responsive alpha-subunit promoter. The response to various concentrations of CRF or PGE1 was identical in control cells and transfected clones containing very little type I kinase. These experiments suggest that in the CRF and PGE1 response pathways leading to gene induction, the magnitude and sensitivity of the response are not influenced by the presence or absence of type I cAMP-dependent protein kinase. PMID- 1744105 TI - Gene structure of mammalian acetylcholinesterase. Alternative exons dictate tissue-specific expression. AB - The genes encoding mouse and human acetylcholinesterases have been cloned from genomic and cosmid libraries. Restriction analysis and a comparison of sequence with the cDNAs have defined the exon-intron boundaries. In mammals, three invariant exons encode the signal peptide and the amino-terminal 535 amino acids common to all forms of the enzyme whereas alternative exon usage of the next exon accounts for the structural divergence in the carboxyl termini of the catalytic subunits. mRNA protection studies show that the cDNA encoding the hydrophilic catalytic subunits represents the dominant mRNA species in mammalian brain and muscle whereas divergent mRNA species are evident in cells of hematopoietic origin (bone marrow cells and a erythroleukemia cell line). Analyses of mRNA species in these cells and the genomic sequence have enabled us to define two alternative exons in addition to the one found in the cDNAs; they encode unique carboxyl-terminal sequences. One mRNA consists of a direct extension through the intervening sequence between the common exon and the 3' exon deduced from the cDNA. This sequence encodes a subunit lacking the cysteine critical to oligomer formation. Another mRNA results from a splice that encodes a stretch of hydrophobic amino acids immediately upstream of a stop codon. This exon, when spliced to the upstream invariant exons, should encode glycophospholipid-linked species of the enzyme. Homologous sequence, identity of exon-intron junctions, and identity of position of the stop codon are seen for this region in mouse and human. Polymerase chain reactions carried out across the expected intron region and mRNA protection studies show that this splice occurs in mouse bone marrow and erythroleukemia cells yielding the appropriate cDNA. PMID- 1744106 TI - A ribosomal calmodulin-binding protein from Dictyostelium. AB - Using 125I-calmodulin as a probe, we have recently identified specific Ca2+/calmodulin-binding proteins in cell extracts from the cellular slime mold, Dictyostelium discoideum: a major 22-kDa activity, a soluble 78/80-kDa protein, and several membrane-associated high Mr proteins (Winckler, T., Dammann, H., and Mutzel, R. (1991) Res. Microbiol. 142, 509-519). cDNA clones for at least two of these proteins have been isolated by ligand screening of a lambda gt11 prophage expression library. Antibodies directed against the lacZ-cDNA-encoded fusion protein from one of the clones recognized a single 22-kDa component in D. discoideum extracts which comigrated with the endogenous 22-kDa calmodulin binding protein. The cDNA-derived nucleotide sequence predicts a protein of Mr 21,659 with 56% sequence identity (69% homology) with rat ribosomal protein L19. The endogenous 22-kDa calmodulin-binding activity was associated with ribosomes. It was found to be an integral constituent of the large ribosomal subunit, since it cosedimented with 60 S ribosomal subunits in sucrose density gradients in the presence of 0.5 M NH4Cl. Our observations point to a physiological role for calmodulin in the Ca2+ regulation of eukaryotic protein synthesis. Support for this comes from recent studies showing inhibition of protein synthesis by calmodulin antagonists in Ehrlich ascites tumor cells (Kumar, R. V., Panniers, R., Wolfman, A., and Henshaw, E.C. (1991) Eur. J. Biochem. 195, 313-319). PMID- 1744107 TI - Role of disulfide bonds in biologic activity of human interleukin-6. AB - We have examined the functional importance of the two disulfide bonds formed by the four conserved cysteines of human interleukin (IL-6). Using a bacterial expression system, we have synthesized a series of recombinant IL-6 mutants in which the constituent cysteines of the first (Cys45-Cys51), second (Cys74-Cys84), or both disulfide bonds of recombinant human interleukin-6 were replaced by other amino acids. Each mutant was partially purified and tested in four representative bioassays. While mutants lacking Cys45 and Cys51 retained activity similar to nonmutated recombinant IL-6, the activity of mutants lacking Cys74 and Cys84 was significantly reduced, especially in assays involving human cell lines. These results indicate that the first disulfide bond of human interleukin-6 is not required for maintenance of normal biologic activity. However, the fact that mutants lacking Cys45 and Cys51 were more active than corresponding cysteine-free mutants indicates that the disulfide bond formed by these residues contributes to biologic activity in the absence of the second disulfide bond. Competition binding studies with representative mutants indicate that their affinity for the human IL-6 receptor parallels their biologic activities on human cells. PMID- 1744108 TI - Bombinin-like peptides with antimicrobial activity from skin secretions of the Asian toad, Bombina orientalis. AB - The structures and hemolytic and bactericidal activities of three bombinin-like peptides, or BLP-1-3, from the skin of Bombina orientalis are described. The peptides were isolated from the skin of B. orientalis and sequenced by tandem mass spectrometry and are amphipathic, cationic peptides of 25-27 amino acids in length. The sequence of the most abundant member (BLP-1) is: Gly-Ile-Gly-Ala-Ser Ile-Leu-Ser-Ala-Gly-Lys-Ser-Ala-Leu-Lys-Gly-Leu- Ala-Lys-Gly-Leu-Ala-Glu-His-Phe Ala-Asn-NH2. All three peptides were found to share considerable, but not complete, homology with bombinin, an antimicrobial, hemolytic peptide first isolated by Michl and Csordas (Csordas, A., and Michl, A. (1970) Monatsh. Chem. 101, 182-189) from the skin of Bombina variegata. The BLPs have been assayed for antibiotic and hemolytic activity and found to be more potent than magainin 2 (a related antimicrobial peptide from Xenopus laevis) in their ability to kill bacteria. However, no significant hemolytic activity was found for these peptides which suggests a selectivity for prokaryotic over eukaryotic membranes. The molecular basis for antibacterial activity is presumed to be due to their predicted amphipathic alpha-helical structures which is supported by circular dichroism measurements that found significant helical content (63-69% alpha helix) in 40% trifluoroethanol. Last, a cDNA library was constructed from the skin of B. orientalis and screened with an oligonucleotide probe complementary to the COOH terminus of BLP-1. Several clones were isolated and sequenced that encode BLP-1 and BLP-3, as well as an additional peptide (BLP-4) that differs by two amino acid substitutions from BLP-3. PMID- 1744109 TI - Effects of gene mutations in lipoprotein and hepatic lipases as interpreted by a molecular model of the pancreatic triglyceride lipase. AB - A molecular model of human pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774) is used to explain the possible structural effects of the amino acid mutations identified to date in the human lipoprotein and hepatic lipase genes. A sequence homology profile was used to evaluate the alignment of the amino acid sequences of all three lipolytic enzymes (Kirchgessner, T. G., Chuat, J.-C., Heinzmann, C., Etienne, J., Guilhot, S., Svenson, K., Ameis, D., Pilon, C., D'Auriol, L., Andalibi, A., Schotz, M. C., Galibert, F., and Lusis, A. J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 9647 9651) with respect to the secondary structure elements identified in the pancreatic lipase. As expected, maximum homology is observed in internal regions namely the hydrophobic strands of the central beta-pleated sheet. This observation strongly supports the hypothesis that all three molecules exhibit a very similar three-dimensional structure, particularly in the N-terminal catalytic domain. There is considerable variation in some of the surface loops connecting the individual strands, whereas others are conserved. It is hypothesized that the most conserved loops located around the active site are responsible for the catalytic function (similar for all three enzymes), whereas those that markedly differ are involved in the regulation at the molecular level, namely the binding of colipase (pancreatic enzyme) and apolipoprotein CII (lipoprotein lipase). The currently available library of hepatic and lipoprotein gene mutations seems to indicate that the majority of mutants disrupt the folding of the polypeptide chain, rather than affect specific constellations in and around the catalytic site or regulatory loops. PMID- 1744110 TI - Copper K-extended x-ray absorption fine structure studies of oxidized and reduced dopamine beta-hydroxylase. Confirmation of a sulfur ligand to copper(I) in the reduced enzyme. AB - The structure of the copper sites in oxidized and reduced dopamine beta hydroxylase has been studied by extended x-ray absorption fine structure spectroscopy using a restrained refinement approach to data analysis. An histidine-rich active site has been found to be present with an average histidine coordination of between two and three histidine ligands per copper. In the oxidized protein, the data support four-coordination, involving two to three imidazole groups at 1.99 A with additional ligands derived from water or exogenous O-donor groups at an average distance of 1.94 A. Studies on the reduced enzyme have focused on resolving the controversy in the literature (Scott, R. A., Sullivan, R. J., De Wolfe, W. E., Dolle, R. E., and Kruse, L. I. (1988) Biochemistry 27, 5411-5417; Blumberg, W. E., Desai, P. R., Powers, L., Freedman, J. H., and Villafranca, J. J. (1989) J. Biol. Chem. 264, 6029-6032) as to whether a S/Cl scatterer is a ligand to Cu(I). Five independent samples of reduced enzyme prepared under conditions designed to probe the Cu(I) ligand environment have been measured and analyzed. All five samples gave identical spectra and could be simulated by two to three imidazoles (1.93 A) and 0.5 S/Cl (2.25 A) per Cu(I). The spectra were insensitive to the presence of added bromide or to exclusion of chloride during preparation. The results establish that the heavy atom scatterer is derived from a sulfur donor. Some evidence was found for an additional O/N scatterer at 2.6 A in the reduced enzyme. A hypothesis for the structure of the copper sites has been proposed involving inequivalent CuA(His)3(H2O)...CuB (His)2X(H2O) coordination in the oxidized enzyme, which upon reduction loses coordinated water and coordinates a sulfur probably from a methionine. PMID- 1744111 TI - Structure-activity relationships of interleukin-8 determined using chemically synthesized analogs. Critical role of NH2-terminal residues and evidence for uncoupling of neutrophil chemotaxis, exocytosis, and receptor binding activities. AB - Interleukin-8 (IL-8) is an inflammatory mediator that stimulates neutrophil migration and functional activation. Analogs of human IL-8 were chemically synthesized, purified, and compared with the full-length 72-residue synthetic IL 8 for their ability to stimulate neutrophil chemotaxis and exocytosis as measured by assaying for release of elastase, as well as their binding to specific receptors in competition assays. Analogs corresponding to the less abundant natural forms, 3-72, 4-72, and 77-residue IL-8, were evaluated and the 3-72 and 4 72 had 2-5-fold higher potencies, whereas the 77-residue IL-8 was 2-fold less potent. A major finding was that NH2-terminal residues 4, 5, and 6 were absolutely essential for IL-8 activity and receptor binding. Quantitative dissociation of elastase release and chemotaxis activity was detected with 5-72, which compared with 1-72, was 80-fold less potent in the elastase assay, but was only slightly less potent in stimulating chemotaxis. IL-8 6-72 lacked all the biological activities tested but had detectable receptor binding activity. The NH2-terminal peptide, AVLPRSAKEL, lacked activity and receptor binding, suggesting that the NH2-terminal region alone is not sufficient for function. Comparison of analogs shortened at the COOH terminus showed that potency was progressively reduced as the COOH-terminal residues were excluded. However activity was retained in an analog (1-51) with the entire COOH-terminal alpha helix and beta turn missing. A peptide corresponding to the COOH-terminal 22 residues, although inactive alone, synergized with the 1-51 analog in stimulating elastase release. The results suggest that the NH2-terminal residues 4, 5, and 6, which are disordered in the IL-8 solution structure, are directly involved in receptor binding, but the COOH-terminal alpha helix is probably important for stabilizing the three-dimensional structure. Other regions within residues 7-51 are also functionally important. PMID- 1744112 TI - An active serine is involved in covalent substrate amino acid binding at each reaction center of gramicidin S synthetase. AB - The condensing peptide forming multienzyme of gramicidin S synthetase (gramicidin S synthetase 2) was specifically labeled at its putative thiotemplate sites for L valine and L-leucine by covalent incorporation of the 14C-labeled substrate amino acids. The thioester complexes of the multienzyme were digested with CNBr, Staphylococcus aureus V8 protease, and pepsin. Reaction center peptides containing the [14C]valine and [14C]leucine labels were isolated in pure form. They show a high degree of sequence similarity and contain the same consensus sequence LGGH/DXL. The labels were eliminated in the first Edman degradation step. A dehydroalanine was identified which can originate from either a cysteine or a serine. The comparison of the chemical results with the deduced amino acid sequence of the grsB gene encoding the gramicidin S synthetase 2 revealed that 4 such motifs are located within the gene structure, each of them being localized in the 3'-terminal region of one of 4 gene segments grsB1-B4. They have a size of approximately 2 kilobases and presumably code for the 4 amino acid activating domains of the synthetase. Surprisingly a serine was found at each putative substrate amino acid-binding position instead of a cysteine as postulated by the thiotemplate mechanism. Therefore the data suggest that active serine residues are involved in nonribosomal peptide syntheses of microbial peptides. PMID- 1744113 TI - Phorbol ester induces manganese-superoxide dismutase in tumor necrosis factor resistant cells. AB - The effects of phorbol ester (TPA) and other known stimulators such as tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide on induction of mRNA for manganese-superoxide dismutase (Mn-SOD) were investigated in various cell lines. TPA enhanced Mn-SOD mRNA expression in TNF-resistant cell lines including HeLa cells, in which the other reagents also induced expression of the gene, but did not affect TNF-sensitive cells, in which the other stimulators did not alter expression of the gene. HeLa cells which had been desensitized to TPA by pretreatment with TPA for 24 h expressed Mn-SOD mRNA at a slightly higher level than the cells without TPA treatment. TPA-pretreated cells stimulated with TNF, however, expressed Mn-SOD mRNA at about twice the level of TNF-stimulated, TPA untreated cells. When protein synthesis was inhibited by cycloheximide during TPA pretreatment, TNF no more enhanced the Mn-SOD mRNA accumulation. These data suggest that at least two separate signal-transducing pathways are involved in expression of this gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulation with TNF, interleukin-1, or lipopolysaccharide and in which a protein factor that can be induced by TPA treatment is involved. PMID- 1744114 TI - fMet-Leu-Phe-induced activation of phospholipase D in human neutrophils. Dependence on changes in cytosolic free Ca2+ concentration and relation with respiratory burst activation. AB - In this study, we have investigated the Ca2+ requirements for the activation of phospholipase D by the tripeptide fMet-Leu-Phe (fMLP) in human neutrophils. EGTA inhibited the activation of phospholipase D (PLD) by 55% (n = 4). When the initial transient rise in [Ca2+]i was prevented by loading the cells with limited amounts of the Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), PLD activation was inhibited by 92% (n = 4). In the presence of both chelators, PLD activation was only 4% of control. In electropermeabilized neutrophils, too, the activation of PLD after the addition of fMLP strongly depends on the Ca2+ concentration, being almost absent with 100 nM free Ca2+ present and reaching maximum activation with a free [Ca2+] of 500 nM. We subsequently investigated the relationship between PLD activation and the activation of the respiratory burst. In neutrophils loaded with BAPTA/AM (10 microM), in which PLD activation was almost absent, a respiratory burst could be induced by fMLP, albeit with a much longer lag time. A respiratory burst could also be elicited by fMLP in electropermeabilized neutrophils incubated with 100 nM free Ca2+. This response, however, was strongly enhanced in the presence of 1 microM Ca2+. Our results indicate that changes in [Ca2+]i are essential for the activation of PLD by fMLP, but probably do not constitute the sole activation signal. In addition, our data provide evidence that PLD activation is important, but not necessary, for activation of the neutrophil respiratory burst. PMID- 1744115 TI - Localization of chromatophore proteins of Rhodobacter sphaeroides. I. Rapid Ca(2+)-induced fusion of chromatophores with phosphatidylglycerol liposomes for proteinase delivery to the luminal membrane surface. AB - A protease delivery system was developed for the exclusive and controlled digestion of proteins exposed at the morphological inside (periplasmic surface) of Rhodobacter sphaeroides chromatophores. In this procedure, proteinase K is encapsulated within large unilamellar liposomes which are fused to the chromatophores in the presence of Ca2+ ions. The liposomes were prepared by a detergent dialysis procedure from native phosphatidylglycerol and found to undergo rapid bilayer fusion with purified chromatophore preparations above a threshold concentration of 12.5 mM CaCl2. The fusion process was complete within 10 min at 35 mM Ca2+ with about 80% of the pigment located in the fusion products. Electron micrographs of freeze-fracture replicas confirmed the intermixing of the lipid bilayers and the unilamellar structure of the fused membrane vesicles. The procedure did not affect the labile B800 chromophore of the B800-850 antenna complex, but reduced slightly the absorption due to the B875 core antenna. Emission from both light-harvesting complexes was increased in the fused membranes, suggesting a partial dissociation of photosynthetic units in the expanded bilayer. The results, together with those presented in the following paper (Theiler, R., and Niederman, R. A. (1991) J. Biol. Chem. 266, 23163-23168), demonstrate that this new method fulfills the stringent requirements for a successful delivery of macromolecules to the chromatophore interior. PMID- 1744116 TI - The poly-N-acetyllactosamines attached to lysosomal membrane glycoproteins are increased by the prolonged association with the Golgi complex. AB - The poly-N-acetyllactosamines on neutrophils and monocytes have been shown to serve as ligands for various selectins present on endothelial cells and platelets. We have previously shown that only a limited number of glycoproteins contain poly-N-acetyllactosamine and found that lysosomal membrane glycoproteins (lamps) are the major glycoproteins carrying poly-N-acetyllactosamine. In order to understand the reason why only certain glycoproteins can be modified by poly-N acetyllactosamine, we have utilized 21 degrees C incubation conditions, which were previously shown to cause the accumulation of glycoproteins at the trans Golgi. HL-60 cells were labeled with [3H]galactose at 21 or 37 degrees C for 6 or 24 h, and lamp-1 and lamp-2 were immunoprecipitated. Upon examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, each lamp from HL-60 cells incubated at 21 degrees C exhibited a much broader, slower migrating band than that isolated from the cells incubated at 37 degrees C. The number of N-glycans containing poly-N-acetyllactosamine, estimated by their binding to tomato lectin column, increased approximately 30-50% after incubation at 21 degrees C than incubation at 37 degrees C. The analysis of oligosaccharides released by endo beta-galactosidase digestion demonstrates that the amount of side chains containing three or more N-acetyllactosamine repeats increased about 100% after incubation at 21 degrees C, and methylation analysis confirmed these results. The same analysis and the results obtained by ion-exchange chromatography also provided evidence that the N-glycans of lamps are sialylated at 21 degrees C as much as at 37 degrees C. Pulse-chase experiments using [35S]methionine labeling indicated that the time necessary for processing of lamps is much longer at 21 degrees C than at 37 degrees C. These results therefore indicate that incubation at 21 degrees C causes the lamps to reside longer within the Golgi complex, and such longer residence allows lamps to acquire more polylactosaminoglycan. These results also suggest that the time necessary for moving through the Golgi complex is a critical factor for poly-N-acetyllactosamine formation. PMID- 1744117 TI - The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme to yeast peroxisomes. AB - The gene encoding Candida tropicalis peroxisomal trifunctional enzyme, hydratase dehydrogenase-epimerase (HDE), was expressed in both Candida albicans and Saccharomyces cerevisiae. The cellular location of HDE was determined by subcellular fractionation followed by Western blot analysis of peroxisomal and cytosolic fractions using antiserum specific for HDE. HDE was found to be exclusively targeted to and imported into peroxisomes in both heterologous expression systems. Deletion and mutational analyses were used to determine the regions within HDE which are essential for its targeting to peroxisomes. Deletion of a carboxyl-terminal tripeptide Ala-Lys-Ile completely abolished targeting of HDE to peroxisomes, whereas large internal deletions of HDE (amino acids 38-353 or 395-731) had no effect on HDE targeting to peroxisomes in either yeast. This tripeptide is similar to, but distinct from, other tripeptide peroxisomal targeting sequences (PTSs) as identified in peroxisomal firefly luciferase and four mammalian peroxisomal proteins. Substitutions within the carboxyl-terminal tripeptide (Ala----Gly and Lys----Gln) supported targeting of HDE to peroxisomes of C. albicans but not of S. cerevisiae. This is the first detailed analysis of the peroxisomal targeting signal in a yeast peroxisomal protein. PMID- 1744118 TI - The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. AB - Cyclophilin (CyP), a major cytosolic protein possessing peptidyl-prolyl cis-trans isomerase activity, has been implicated as the specific receptor of the immunosuppressive drug cyclosporin A (CsA). To identify other potential CsA receptors related to CyP, two human cDNA libraries were screened under low stringency conditions using human CyP cDNA (encoding hCyP1) as a probe. Two cDNAs were identified which encode distinct proteins related to human hCyP1. These two novel proteins, designated hCyP2 and hCyP3, share 65 and 76% amino acid sequence homology with hCyP1, respectively. Both hCyP2 and hCyP3 contain NH2-terminal hydrophobic extensions of 32 and 42 amino acids, respectively. Protein-specific antibodies revealed the predominant association of hCyP2 and hCyP3 with membranes and subcellular organelles, which suggests that the amino-terminal leader sequences of the two CyP isoforms may act as signal peptides. In contrast to the results with hCyP1, Southern blot analysis indicated that both hCyP2 and hCyP3 gene sequences are represented infrequently in the human genome. Northern and Western blot analysis showed that the distribution of mRNA and proteins of the three hCyPs in differing tissues and cell types was similar. Each hCyP protein was expressed in Escherichia coli, purified, and shown to be an active peptidyl prolyl isomerase. Substrate specificity was examined with 11 synthetic peptides (Suc-Xaa-Yaa-Pro-Phe-4-nitroanilide), and inhibition of the peptidyl-prolyl isomerase activities associated with hCyP1, hCyP2, and hCyP3 was studied with CsA, MeAla6-CsA and MeBm2t1-CsA. From both equilibrium considerations and the results of kinetic characterizations it is proposed that of these three CyP proteins, hCyP1 is the most likely intracellular target for CsA. PMID- 1744119 TI - Requirements for primer synthesis by bacteriophage T7 63-kDa gene 4 protein. Roles of template sequence and T7 56-kDa gene 4 protein. AB - Gene 4 of bacteriophage T7 encodes two proteins, a 63-kDa protein and a colinear 56-kDa protein, that are essential for synthesis of leading and lagging strands during DNA replication. The gene 4 proteins together catalyze the synthesis of oligoribonucleotides, pppACC(C/A) or pppACAC, at the single-stranded DNA sequences 3'-CTGG(G/T)-5' or 3'-CTGTG-5', respectively. Purified 56-kDa protein has helicase activity, but no primase activity. In order to study 63-kDa gene 4 protein free of 56-kDa gene 4 protein, mutations were introduced into the internal ribosome-binding site responsible for the translation of the 56-kDa protein. The 63-kDa gene 4 protein was purified 16,000-fold from Escherichia coli cells harboring an expression vector containing the mutated gene 4. Purified 63 kDa gene 4 protein has primase, helicase, and single-stranded DNA-dependent dTTPase activities. The constraints of primase recognition sequences, nucleotide substrate requirements, and the effects of additional proteins on oligoribonucleotide synthesis by the 63-kDa gene 4 protein have been examined using templates of defined sequence. A three-base sequence, 3'-CTG-5', is necessary and sufficient to support the synthesis of pppAC dimers. dTTP hydrolysis is essential for oligoribonucleotide synthesis. Addition of a 7-fold molar excess of 56-kDa gene 4 protein to 63-kDa protein increases the number of oligoribonucleotides synthesized by 63-kDa protein 100-fold. The increase in oligonucleotides results predominantly from an increase in the synthesis of tetramers, with relatively little change in the synthesis of dimers and trimers. The presence of 56-kDa protein also causes 63-kDa protein to synthesize "pseudo templated" pppACCCC pentamers at the recognition sequence 3'-CTGGG-5'. T7 gene 2.5 protein, a single-stranded DNA binding protein, increases the total number of oligoribonucleotides synthesized by 63-kDa gene 4 protein on single-stranded M13 DNA, but has no effect on the ratio of dimers to trimers and tetramers. PMID- 1744120 TI - Stimulation of endothelin-1 gene expression by insulin in endothelial cells. AB - The present study characterized the regulation of the genetic expression of the vasoactive peptide endothelin-1 (ET-1) by insulin in bovine aortic endothelial cells. By RNA blot analysis, insulin (1.67 x 10(-8) M) increased ET-1 mRNA levels by 2.3-fold over the basal within 10 min and attained a maximum (5.3-fold increase) in 2 h. Dose-response studies showed that a maximum effect of insulin was reached at 1.67 x 10(-8) M although a significant increase can be observed at 1.66 x 10(-9) M. Radioligand receptor studies indicated that the affinity constant for insulin receptors on endothelial cells correlated closely with the dose response observed for ET-1 mRNA. The ET-1 mRNA half-life was estimated with actinomycin D studies to be 20 min in control cells and was not affected by insulin treatment. Moreover, the effects of phorbol 12-myristate 13-acetate (PMA) and insulin were additive in the induction of ET-1 gene expression. When protein kinase C in the bovine aortic endothelial cells was down-regulated by preincubation with 8 x 10(-7) M PMA for 24 or 48 h, insulin was still able to increase ET-1 mRNA levels whereas PMA was ineffective. Using a chloramphenicol acetyltransferase (CAT) fusion plasmid containing the CAT gene and the 5' flanking region of the ET-1 gene (Lee, M. E., Bloch, K. D., Clifford, J. A., and Quertermous, T. (1990) J. Biol. Chem. 265, 10446-10450), we observed that 1.67 x 10(-8) M insulin increased CAT enzyme activity and mRNA levels. The insulin dose response curve observed for CAT activity correlated with that observed for ET-1 mRNA levels. These results suggest that insulin stimulates expression of the ET-1 gene at the transcriptional level via its own receptors. This effect is mediated mostly through a protein kinase C-independent pathway, suggesting the existence of an insulin-responsive element in the ET-1 gene 5'-flanking sequence. PMID- 1744121 TI - Synthesis and characterization of 5-azido-UDP-glucuronic acid. A new photoaffinity probe for UDP-glucuronic acid-utilizing proteins. AB - A new active site-directed photoaffinity analogue, [beta-32P]5-azido-UDP glucuronic acid (UDP-GlcA), was enzymatically synthesized from [beta-32P]5-N3UDP Glc using UDP-glucose dehydrogenase. The product was characterized by its mobility on ion exchange and two thin-layer chromatographic systems, by its UV absorbance at 288 nm, and the loss of this absorbance after UV irradiation of the compound. Photoincorporation of [beta-32P]5-N3UDP-GlcA into bovine liver UDP-Glc dehydrogenase (EC 1.1.1.22) was saturable with an apparent Kd of 12.5 microM, and was inhibited by the known active-site effectors UDP-GlcA, UDP-Glc, and UDP xylose. When human liver microsomes with known UDP-glucuronosyltransferase (EC 2.4.1.17) activities were photolabeled with [beta-32P]5-N3UDP-GlcA, major photolabeled bands of 35-37 and 50-54 kDa were detected. When rat liver microsomes from phenobarbital-injected rats were photolabeled with [beta-32P]5 N3UDP-GlcA, there was a marked increase in photoincorporation of a 51-kDa protein as compared with control animals. Evidence is presented which suggests that the photolabeled 51-54-kDa proteins in the liver microsomes from both tissues are UDP glucuronosyltransferase and that [beta-32P]5-N3UDP-GlcA represents a new alternative approach in the study of UDP-glucuronosyltransferase and other UDP GlcA-utilizing enzymes. PMID- 1744122 TI - A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase related protein. AB - The profound influence of glucocorticoid hormones on the inflammatory response includes a rapid and significant reduction in the synthesis of cyclooxygenase (prostaglandin G/H synthase, PGHS), the key enzyme for prostaglandin biosynthesis. In analyzing the glucocorticoid effects on PGHS synthesis in C127 mouse fibroblasts, we detected a novel 4-kilobase (kb) mRNA that is related to a PGHS cDNA cloned from an ovine seminal vesicle library. This RNA is much more prevalent in cycloheximide-treated cells and, based on stringency analysis and preliminary sequence data, arises from a gene distinct from that transcribed into the previously cloned 2.8-kb PGHS cDNA. Furthermore, the 4-kb mRNA encodes a 70 kDa protein that is specifically immunoprecipitated by anti-PGHS serum. The abundance of the 4-kb mRNA is strongly decreased by dexamethasone and increased by serum within 2 h whereas the 2.8-kb PGHS mRNA, which is also seen in these cells, does not consistently change. These changes in the level of the 4-kb mRNA with serum and dexamethasone treatment parallel changes in the level of synthesized PGHS protein detected in both metabolically labeled cells and in in vitro translated mRNAs. This discovery of a cyclooxygenase-related gene that is transcriptionally regulated by serum and glucocorticoid hormones in a manner identical to that reported for cyclooxygenase activity may help clarify issues regarding cyclooxygenase regulation and suggests that two distinct and differentially regulated cyclooxygenase species exist. PMID- 1744123 TI - Concerted modulation of alpha 1(XI) and alpha 2(V) collagen mRNAs in bovine vascular smooth muscle cells. AB - We have isolated a partial cDNA for alpha 1(XI) collagen from a bovine smooth muscle cell (SMC) library. Previously, this collagen was not known to be expressed in SMCs. Comparison of the nucleotide and deduced amino acid sequence of the 2.7-kilobase bovine clone and the human alpha 1(XI) sequence indicates 92 and 98% homology, respectively. Bovine SMCs in culture were found to produce alpha 1(XI) mRNA. However, alpha 2(XI) and alpha 1(II) collagen RNA were not detectable; therefore, SMCs cannot synthesize the same type XI collagen as found in cartilage. Since type XI collagen is structurally related to type V collagen, the expression of alpha 1(XI) and alpha 2(V) collagen mRNA in SMCs was characterized. Levels of alpha 1(XI) and alpha 2(V) collagen mRNAs were low in exponentially growing SMCs and increased 3-4-fold as cells became confluent. Increased mRNA levels were also observed when exponentially growing subconfluent SMCs were incubated in medium containing 0.5% fetal bovine serum for 24 h, similar to the effects of serum deprivation on the expression of types I and III collagen genes (Kindy, M. S., Chang, C.-J., and Sonenshein, G. E. (1988) J. Biol. Chem. 263, 11426-11430). However, as cell density increased, serum deprivation resulted in very different responses for these collagen genes. Serum deprivation caused a decrease in expression of alpha 1(XI) and alpha 2(V) collagen mRNAs in cultures as they approached confluence. In contrast, at confluence alpha 1(I) and alpha 2(I) mRNA levels no longer responded to serum concentration whereas expression of alpha 1(III) mRNA remained inducible by serum deprivation. These results suggest concerted regulation of alpha 1(XI) and alpha 2(V) collagen gene expression, which is distinct from that for the chains of type I and type III collagen with respect to cell density and serum. PMID- 1744124 TI - Differential expression of small chondroitin/dermatan sulfate proteoglycans, PG I/biglycan and PG-II/decorin, by vascular smooth muscle and endothelial cells in culture. AB - Cultured bovine aortic smooth muscle (BASM) and endothelial (BAE) cells, like articular chondrocytes, synthesize two populations of small chondroitin/dermatan sulfate (CS/DS) proteoglycans (PGs) of similar size as PG-I/biglycan and PG II/decorin. However, Northern blot analyses demonstrated that BAE cells express detectable amounts of mRNA transcripts only for PG-I/biglycan, whereas BASM cells and articular chondrocytes express mRNA transcripts for both PG-I/biglycan and PG II/decorin. Endothelial cells from human umbilical vein also expressed detectable amounts of mRNA transcripts only for PG-I/biglycan, and not PG-II/decorin. Antiserum raised against bovine PG-II/decorin immunoprecipitated an apparent single PG species with relative molecular mass (Mr) of approximately 120,000 180,000 from BASM cell and articular chondrocyte cultures but failed to immunoprecipitate an equivalent PG species from BAE cell cultures, consistent with the results from Northern blot analysis. In contrast, immunoprecipitations by antisera to PG-I/biglycan indicated that cultured endothelial cells synthesize two forms of PG-I/biglycan with Mr values slightly larger than 200,000 and 120,000-140,000. It is likely, based on the magnitude of the size difference, that these two forms of PG-I/biglycan differ in the number of glycosaminoglycan chains. Additionally, BASM but not BAE cells were found to express detectable amounts of mRNA transcripts for type I collagen. The above results indicate that the two main cell types of the vascular wall, endothelial and smooth muscle cells, express different sets of small interstitial CS/DS PGs and that the synthesis of PG-II/decorin by these cells correlates with the expression of type I collagen, a collagen known to interact specifically with this PG. These differences in the expression of extracellular matrix molecules may be important in regulating the cell type-specific functions of endothelial and smooth muscle cells within the vascular tissue. PMID- 1744125 TI - Purification of the transforming growth factor-beta (TGF-beta) binding proteoglycan betaglycan. AB - We report the purification of betaglycan, a low-abundance membrane proteoglycan with high affinity for transforming growth factor-beta (TGF-beta). Betaglycan solubilized from rat embryo membrane preparations was purified to near homogeneity by sequential chromatography through DEAE-Trisacryl, wheat germ lectin-Sepharose, and TGF-beta 1-agarose. Purified betaglycan has properties similar to betaglycan affinity-labeled in intact cells: it binds TGF-beta 1 and TGF-beta 2 with KD approximately 0.2 nM, contains heparan sulfate and chondroitin sulfate glycosaminoglycan (GAG) chains and N-linked glycans attached to a 110-kDa core protein, and can spontaneously associate with phosphatidylcholine liposomes. The betaglycan core obtained by enzymatic removal of the GAG chains has high affinity for TGF-beta and associates with artificial liposomes, indicating that the core protein binds TGF-beta and anchors to membranes independently of the GAG chains present on the native protein or of any ancillary protein. PMID- 1744126 TI - Multiple origins of the human glycophorin Sta gene. Identification of hot spots for independent unequal homologous recombinations. AB - Human glycophorin Sta (HGpSta), one of the structural variants of erythrocyte membrane sialoglycoproteins, is encoded by a delta-alpha hybrid gene that arose from a single unequal crossover between the parent HGpB(delta) and HGpA(alpha) genes. We report here the identification of two new HGpSta genes (type A and type B) in four unrelated Sta heterozygotes from two ethnic groups. These Sta genes represent distinct genetic isoforms that differ from the previously reported Sta gene (type C) in the location of crossing-over sites. Comparison of nucleotide sequences among HGpB(delta), HGpA(alpha), and HGpSta type A genes revealed that the delta-alpha unequal crossover for the Sta type A gene occurred 110-246 base pairs downstream from pseudoexon III. In the crossing-over site of this Sta gene, an AT-rich sequence lying 3' to a nonameric palindrome was found to be highly similar to the lambda phage attachment site, att B, in inverted orientation. In the Sta type B gene, the delta-alpha crossing-over point was localized to an AG rich sequence that is 302-490 base pairs downstream from pseudoexon III. Multiple lambda chi-like elements were identified at the crossover boundaries and within the breakpoint of this Sta gene. These results suggest strongly that recurrent and independent unequal recombination events have occurred in the formation of multiple Sta genes and that particular genomic sequences are important in defining the recombination sites for these homology-driven processes. PMID- 1744127 TI - The Drosophila RBP-J kappa gene encodes the binding protein for the immunoglobulin J kappa recombination signal sequence. AB - We previously isolated a cDNA encoding the 60-kDa murine protein (RBP-J kappa protein) that specifically binds to the immunoglobulin J kappa recombination signal sequence. The RBP-J kappa gene is highly conserved in a wide variety of organisms including man, Xenopus, Drosophila, and yeast. We have isolated and characterized the Drosophila homologue of the RBP-J kappa gene. The Drosophila RBP-J kappa gene was mapped to the polytene region 35BC of chromosome 2. The nucleotide sequence of this gene indicates that it is not one of the known genes located in the 35 BC region. The nucleotide and amino acid sequences of the Drosophila and mouse RBP-J kappa genes are 60 and 75% homologous, respectively. The central 248-residue regions of RBP-J kappa proteins of the two species are 93% homologous and include the 40-residue integrase motif. The Drosophila RBP-J kappa protein expressed in COS cells bound to the J kappa recognition sequence with the same specificity as the murine counterpart. These results suggest that Drosophila may have a site-specific recombination system which utilizes the immunoglobulin recombination signal sequence. Implications for evolution of immunoglobulin gene rearrangement were also discussed. PMID- 1744128 TI - Hypoxia enhances phosphorylation of eukaryotic initiation factor 4A in maize root tips. AB - We have identified two isoforms of initiation factor 4A (eIF-4A) in maize root tips, with distinct isoelectric points and similar molecular mass (approximately 50 kDa). Both isoforms of maize eIF-4A cross-react with antibodies raised against wheat germ eIF-4A, and one of the maize proteins (higher pI isoform) comigrates with purified wheat germ eIF-4A on two-dimensional gels. The two maize eIF-4As were indistinguishable by comparative peptide fingerprint analysis, which also showed a very strong similarity between eIF-4A in maize roots and wheat germ. Maize eIF-4As copurify with eIF-4F and eIF-(iso)4F on a 7-methyl-GTP-Sepharose affinity column, indicating that they are part of the 5'-cap-binding complex. Two dimensional gel electrophoresis and immunoblotting of proteins from 32P-labeled maize root tips revealed that the lower pI isoform of eIF-4A is phosphorylated. Two-dimensional phosphopeptide maps of trypsin-digested eIF-4A contained one principal phosphorylated fragment; phosphoamino acid analysis indicated phosphorylation of threonine. In oxygenated maize root tips, the ratio of phosphorylated to nonphosphorylated eIF-4A is approximately 0.2. This ratio increases to approximately 1 within 20 min following the onset of hypoxia, due to interconversion between the two maize eIF-4A isoforms. The hypoxia-induced phosphorylation of eIF-4A is discussed with respect to metabolic responses, and the translational control of gene expression, in hypoxic plant tissues. PMID- 1744129 TI - Cloning and characterization of a testis-specific thymosin beta 10 cDNA. Expression in post-meiotic male germ cells. AB - Thymosin beta 10 is one of a small family of proteins closely related in sequence to thymosin beta 4, recently identified as an actin-sequestering protein. A single molecular weight species of thymosin beta 10 mRNA is present in a number of rat tissues. In adult rat testis, an additional thymosin beta 10 mRNA of higher molecular weight was identified. Nucleotide sequencing of cDNA clones complementary to the testis-specific thymosin mRNA indicated that this mRNA differed from the ubiquitous thymosin beta 10 mRNA only in its 5'-untranslated region, beginning 14 nucleotides upstream of the translation initiation codon. These results, together with primer extension experiments, suggest that the two thymosin beta 10 mRNAs are transcribed from the same gene through a combination of differential promoter utilization and alternative splicing. The novel thymosin beta 10 mRNA could be detected only in RNA isolated from sexually mature rat testis. Both mRNAs were present in pachytene spermatocytes; only the testis specific mRNA was detected in postmeiotic haploid spermatids. Immunoblot analysis using specific antibodies showed that the thymosin beta 10 protein synthesized in adult testis was identical in size to that synthesized in brain. Immunohistochemical analysis showed that the protein was present in differentiating spermatids, suggesting that the testis-specific thymosin beta 10 mRNA is translated in haploid male germ cells. PMID- 1744130 TI - Structure of the agonist-binding site of the nicotinic acetylcholine receptor. [3H]acetylcholine mustard identifies residues in the cation-binding subsite. AB - To characterize the structure of the agonist-binding site of the Torpedo nicotinic acetylcholine receptor (AChR), we have used [3H]acetylcholine mustard [( 3H]AChM), a reactive analog of acetylcholine, to identify residues contributing to the cation-binding subsite. Reaction of [3H]AChM, in its aziridinium form, with AChR-rich membrane suspensions, resulted initially in reversible, high affinity binding (K approximately 0.3 microM) followed by slow alkylation of the acetylcholine-binding site. Incorporation of label into AChR alpha-subunit was inhibited by agonists and competitive antagonists, but not by noncompetitive antagonists, and reaction with 3 microM [3H]AChM for 2 h resulted in specific alkylation of 0.6% of alpha-subunits. Within the alpha-subunit, greater than 90% of specific incorporation was contained within an 18-kDa Staphylococcus aureus V8 proteolytic fragment beginning at Val-46 and containing N-linked carbohydrate. To identify sites of specific alkylation, [3H]AChM-labeled alpha-subunit was digested with trypsin, and the digests were fractionated by reverse phase high pressure liquid chromatography. Specifically labeled material was recovered within a single peak containing a peptide extending from Leu-80 to Lys-107. NH2-terminal amino acid sequencing revealed specific release of 3H in cycle 14 corresponding to alpha-subunit Tyr-93. Identification of Tyr-93 as the site of alkylation was confirmed by radiosequence analysis utilizing o phthalaldehyde to establish that the released 3H originated from a peptide containing prolines at residues 2 and 9. Because [3H]AChM contains as its reactive group a positively charged quaternary aziridinium, alpha-subunit Tyr-93 is identified as contributing to the cation-binding domain of the AChR agonist binding site. The selective reaction of [3H]AChM with tyrosyl rather than acidic side chains indicates the importance of aromatic interactions for the binding of the quaternary ammonium group, and the lack of reaction with the tyrosyl or acidic side chains within alpha 190-200 emphasizes the selective orientation of acetylcholine within its binding site. PMID- 1744131 TI - Transgenic mice that express a mini-gene version of the human gene for type I procollagen (COL1A1) develop a phenotype resembling a lethal form of osteogenesis imperfecta. AB - A mini-gene version of the human gene for a pro-alpha 1(I) chain of type I procollagen (COL1A1) was prepared that contained -2.5 kilobases of the promoter region and the 5'- and 3'-ends of the gene but lacked a large central region containing 41 exons. The construct was modeled after a sporadic in-frame deletion of the human gene that produced a lethal variant of osteogenesis imperfecta, because it caused synthesis of shortened pro-alpha 1(I) chains that associated with normal pro-alpha 1(I) and pro-alpha 2(I) chains and caused degradation of both the shortened and normal pro-alpha chains through a process called procollagen suicide. The mini-gene was used to prepare transgenic mice. Eight of 15 transgenic mice expressed varying levels of the gene. All except one of the Fo founders were phenotypically normal, but several of the founders were apparently mosaic since they produced F1 progeny that died shortly after birth with a distinctive phenotype. The phenotype included extensive fractures of ribs and long bones similar to the fractures seen in lethal variants of osteogenesis imperfecta. Mice with the lethal phenotype expressed much higher levels of the mini-gene than transgenic mice without the lethal phenotype. Experiments with cultured skin fibroblasts from the transgenic mice demonstrated that shortened pro-alpha 1(I) chains synthesized from the mini-gene became disulfide-linked to pro-alpha 1(I) chains synthesized from the endogenous mouse gene. The results demonstrate that a mutated type I procollagen gene based on the model of procollagen suicide can be used to produce a severe phenotype of osteogenesis imperfecta that is genetically transmitted. PMID- 1744132 TI - Isolation and functional properties of an arginine-selective endoprotease from rat intestinal mucosa. A putative prosomatostatin convertase. AB - The endoproteolytic activity previously detected in rat intestinal mucosal extracts (Beinfeld M., Bourdais, J., Kuks, P., Morel, A., and Cohen, P. (1989) J. Biol. Chem. 264, 4460-4465), was purified to homogeneity as a 65-kDa molecular species. This putative proprotein-processing enzyme cleaves the peptide bond on the carboxyl side of a single arginine residue in hepta-[Leu62-Gln-Arg-Ser-Ala Asn-Ser68] or trideca-[Asp56-Glu-Met-Arg-Leu-Glu-Leu-Gln-Arg-Ser-Ala-Asn-+ ++Ser68] peptides, reproducing the prosomatostatin sequence around Arg64, the locus for endoproteolytic release of either somatostatin-28 or its NH2-terminal fragment, somatostatin-28-(1-12), from their common precursor. This enzyme exhibits a strict selectivity for arginyl residues, as demonstrated with related substrates, and did not cleave at lysyl residues. Moreover, only arginyl residues belonging to peptides of the prosomatostatin family were cleaved, since no hydrolysis of peptides from other prohormones was detected. In addition, the arginine residue situated at position -5 on the NH2-terminal side of Arg64 not only did not function as a cleavage locus, but had no effect on the overall cleavage kinetics of the prosomatostatin-(56-68) peptide substrate. This enzyme also cleaved, but with much less efficiency, the peptide bond on the carboxyl side of an arginine in peptides containing either an Arg-Lys or a Lys-Arg doublet corresponding to prohormone cleavage sites. This enzyme was insensitive to divalent cation chelators, was completely inhibited by aprotinin and leupeptin, and was somewhat inhibited by other serine-protease inhibitors. It is concluded that this endoprotease is a serine protease and could be involved in prohormone or proprotein post-translational processing at single arginine cleavage sites. PMID- 1744133 TI - Binding of elastin to Staphylococcus aureus. AB - Many pathogenic bacteria specifically bind to components of the extracellular matrix. In this study, we report the specific association of Staphylococcus aureus with elastin, a major structural component of elastic tissue. Competition assays in which the binding of radiolabeled tropoelastin was inhibited by excess unlabeled elastin peptides, but not by other proteins, established the specificity of the interaction. Kinetic studies showed that tropoelastin binding to the bacteria was rapid and saturable. Scatchard analysis of the equilibrium binding data indicated the presence of a single class of high affinity binding sites (KD approximately 4-7 nM) with approximately 1000 sites per organism. Protease susceptibility suggested that the elastin binding moiety on S. aureus was a protein, which was confirmed by the isolation of a 25-kDa elastin-binding protein from S. aureus extracts through affinity chromatography. Using a truncated form of tropoelastin, the bacterial binding domain on elastin was mapped to a 30-kDa fragment at the amino end of the molecule. Although the precise amino acid sequence recognized by the staphylococcal elastin receptor has not been characterized, it is clearly different from the region of tropoelastin that specifies binding to mammalian elastin receptors. PMID- 1744134 TI - In vivo restriction. Sequence and structure of endonuclease II-dependent cleavage sites in bacteriophage T4 DNA. AB - Endonuclease II of bacteriophage T4 is required for in vivo restriction of cytosine-containing DNA from its host, Escherichia coli, (as well as from phage mutants lacking cytosine modification), normally the first step in the reutilization of host DNA nucleotides for synthesis of phage DNA in infected cells. The phage cytosine-DNA is fragmented incompletely to yield genetically defined fragments. This restriction is different from that of type I, II, or III restriction enzymes. We have located seven major endonuclease II-dependent restriction sites in the T4 genome, of which three were analyzed in detail; in addition, abundant sites were cleaved in less than or equal to 5% of all molecules. Sites I, II, and III shared the sequence 5'-CCGNNTTGGC-3' and were cleaved in about 25% (I and III) and 65% (II) of all molecules, predominantly staggered around the first or second of the central unspecified base pairs to yield fragments with one 5' base. The less frequently cleaved sites I and III deviated from site II in predicted helical structure when viewed from the consensus strand, and in sequence when viewed from the opposite strand. Thus, interaction with a particular helical structure as well as recognition of the bases in DNA appears important for efficient cleavage. PMID- 1744135 TI - Characterization and molecular cloning of a proenzyme form of a ribosome inactivating protein from maize. Novel mechanism of proenzyme activation by proteolytic removal of a 2.8-kilodalton internal peptide segment. AB - Ribosome-inactivating proteins (RIPs) are a widely distributed family of plant enzymes that are remarkably potent catalytic inactivators of eukaryotic protein synthesis. All RIPs described to date, including the A-chain of the plant cytotoxin ricin, are polypeptides of 25-32 kDa and share significant amino acid sequence homologies. We have characterized and cloned an RIP from maize (Zea mays). In contrast to previously described RIPs, we have found that maize RIP is synthesized and stored in the kernel as a 34-kDa inactive precursor (isoelectric point = 6.5). During germination, this neutral precursor is converted into a basic, active form (isoelectric point greater than 9) by limited proteolysis, which removes 25 amino acids (2.8 kDa) of net charge -6 from the center of the polypeptide chain. Additional processing also occurs at the amino and carboxyl termini of the polypeptide. The sequence of the internal processed region is unique and it is equivalent to an insertion centered around Thr-156 in the amino acid sequence of ricin toxin A-chain, i.e. in the center of the enzymatically active domain. The generation of an active enzyme by removal of a large amino acid segment from the middle of a precursor polypeptide chain represents a novel mechanism of proenzyme activation that is distinct from more conventional activation mechanisms involving NH2-terminal proteolytic processing. A two-chain active RIP (comprised of 16.5- and 8.5-kDa fragments that remain tightly associated) is produced from this processing event. PMID- 1744136 TI - Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells. AB - Exposure to ethanol for several days increases the number and function of dihydropyridine-sensitive Ca2+ channels in excitable tissues. In the neural cell line PC12, this process is blocked by inhibitors of protein kinase C (PKC), suggesting that PKC mediates ethanol-induced increases in Ca2+ channels. We report that treatment with 25-200 mM ethanol for 2-8 days increased PKC activity in PC12 cells and NG108-15 neuroblastoma-glioma cells. Detailed studies in PC12 cells showed that ethanol also increased phorbol ester binding and immunoreactivity to PKC delta and PKC epsilon. These changes were associated with increased PKC-mediated phosphorylation. Ethanol did not activate the enzyme directly, nor did ethanol increase levels of diacylglycerol. Ethanol-induced increases in PKC levels may promote up-regulation of Ca2+ channels, and may also regulate the expression and function of other proteins involved in cellular adaptation to ethanol. PMID- 1744137 TI - Characterization of trypsin-sensitive factor(s) required for endosome-endosome fusion. AB - Fusion of endosomes appears to be required at early steps of receptor-mediated endocytosis. These fusion events have been reconstituted using a cell-free assay and have been shown to require both cytosolic and membrane-associated proteins. We report here that trypsinization of endosomes completely inhibited fusion. Addition of untreated cytosol cannot restore fusion of trypsinized endosomes. However, fusion activity is restored by the addition of either untreated vesicles or a high salt extract containing peripheral membrane proteins (KE). KE contains both the membrane-associated factor(s) required for the reconstitution of fusion using trypsinized endosomes and the factors that are normally provided by the cytosol. The restorative activity of KE was sensitive to trypsin treatment or incubation at 100 degrees C, but was largely N-ethylmaleimide (NEM)-resistant. This and other criteria demonstrated that the trypsin-sensitive factor is distinct from N-ethylmaleimide-sensitive factor (NSF), an NEM-sensitive protein involved in vesicular fusion, and from other known factors that may participate in membrane fusion events. Preliminary fractionation studies indicate that the restorative activity of KE is associated with one or more high molecular weight proteins. The present study indicates that a novel trypsin-sensitive protein(s) is involved in endosome-endosome fusion. This factor is membrane-associated and is not found in an active form in cytosol as prepared. PMID- 1744138 TI - Type II collagen mRNA containing an alternatively spliced exon predominates in the chick limb prior to chondrogenesis. AB - A series of cDNA clones corresponding to the 5' end of the chicken type II collagen mRNA were generated using a single-sided polymerase chain reaction technique. Analysis of these cDNAs showed that the second exon of the gene is alternatively spliced such that it is either present or absent in the mRNA. This exon encodes a 70-amino acid cysteine-rich globular domain which is present in the amino-terminal propeptides of alpha 1(I), alpha 1(III), and alpha 2(V) procollagen chains but which was previously thought to be absent from type II procollagen. Analysis of the expression of the two alternatively spliced forms of the chicken type II collagen mRNA showed that the mRNA without the second exon was the predominant form (approximately 90%) in sternal cartilage from 14-day embryos, but in precartilage limb mesenchyme only the form including the second exon was detected. This later form was also present in a number of non-cartilage tissues including embryonic calvaria, skin, heart, skeletal muscle, and brain; no type II collagen mRNA was detected in liver. Studies of developing limbs from progressive embryonic stages suggest that the appearance of the mRNA lacking the second exon is a relatively late event during chondrogenesis. PMID- 1744139 TI - Ligand-induced internalization and increased cell calcium are mediated via distinct structural elements in the carboxyl terminus of the epidermal growth factor receptor. AB - Signals that can mediate ligand-induced receptor internalization and calcium regulation are present in a 48-amino acid "calcium-internalization" domain in the C' terminus of the epidermal growth factor (EGF) receptor. The basis of calcium and internalization regulation signalled by this 48-amino acid sequence was analyzed using deletion and substitution mutant receptors. Cells expressing truncated receptors containing either the NH2- or COOH-terminal portion of the 48 residue domain displayed high affinity EGF-dependent endocytosis and receptor down-regulation. These endocytosis-competent EGF receptor mutants that lacked any autophosphorylation site were unable to increase the concentration of intracellular calcium. To investigate the role of self-phosphorylation in EGF induced calcium mobilization, phenylalanine was substituted for the single autophosphorylated tyrosine residue in this region of an internalization competent truncated receptor. The receptor-mediated calcium response was abolished, while ligand-dependent receptor internalization was unimpaired. These results demonstrate that EGF-dependent receptor endocytosis and calcium mobilization are separate events. Tyrosine self-phosphorylation is required for increased [Ca2+]i, while structural features distinct from autophosphorylation are required for receptor internalization. PMID- 1744140 TI - Protein kinase activity required for an early step in interferon-alpha signaling. AB - Interferon-alpha (IFN alpha) induces an immediate transcriptional response of a restricted set of genes in target cells. Specific transcription is mediated by the cytoplasmic activation of a transcription factor complex termed ISGF3. ISGF3 is a multimeric protein complex composed of a regulatory component (ISGF3 alpha), which is activated following IFN alpha treatment, and a DNA-binding component (ISGF3 gamma), which recognizes the IFN alpha-stimulated response element (ISRE). Following activation, ISGF3 alpha translocates to the nucleus where ISGF3 assembles as a high affinity complex on the ISRE. The biochemical basis for receptor-mediated activation of ISGF3 is unknown. We report that two potent protein kinase inhibitors, staurosporine and K-252a, ablated the transcriptional response to IFN alpha treatment. These inhibitors prevented the activation of the ISGF3 alpha component without affecting the ISGF3 gamma component, resulting in no accumulation of mature ISGF3 in nuclei of treated cells. Although these agents are potent inhibitors of protein kinase C (PKC), PKC does not mediate ISGF3 alpha activation. Down-regulation of PKC by chronic exposure of cells to 12-O tetradecanoylphorbol-13-acetate, which led to complete loss of PKC-immunoreactive material, failed to ablate the transcriptional response to IFN alpha or the activation of ISGF3 alpha. The PKC-specific inhibitor calphostin C did not perturb activation or nuclear accumulation of ISGF3. We conclude that a novel, staurosporine/K-252a-sensitive kinase is required for ISGF3 activity and may participate in receptor-mediated signal transduction. PMID- 1744141 TI - Study of the endoproteolytic cleavage of platelet glycoprotein IIb using oligonucleotide-mediated mutagenesis. AB - The precursor of platelet membrane glycoprotein IIb (GPIIb) undergoes endoproteolytic cleavage into heavy and light chains post-translation. Endoproteolysis occurs within a 17-amino acid stretch of the precursor that contains 4 arginine residues, 3 in dibasic sequences [Lys-Arg (855-856) and Arg Arg (858-859)] and a single arginine at 871. To determine the site of GPIIb cleavage and its role in the function of the glycoprotein IIb/IIIa heterodimer, we mutated arginine 856, the di-arginine sequence 858-859, and arginine 871 and coexpressed the mutants with glycoprotein IIIa (GPIIIa) in COS-1 cells. Each GPIIb mutant formed recombinant GPIIb-IIIa heterodimers, but mutants lacking arginine at 856 or 858-859 failed to undergo cleavage. Nevertheless, heterodimers containing the uncleaved GPIIb were expressed on the cell surface. Because endoproteolysis most often occurs after arginines in dibasic sequences, we next expressed GPIIb mutants containing lysine at 856 or aspartic acid at 855 with GPIIIa. Both mutants were cleaved and surface-expressed, indicating that the dibasic sequence at 858-859, but not at 855-856, is required for GPIIb cleavage. Lastly, we tested the function of GPIIb-IIIa containing uncleaved GPIIb by measuring adhesion of transfected cells to immobilized fibrinogen. We found no difference in the adhesion of cells expressing either wild-type or mutant GPIIb, indicating GPIIb-IIIa heterodimers containing uncleaved GPIIb maintain their ability to interact with fibrinogen. PMID- 1744142 TI - Regulation of integrin-type cell adhesion receptors by cytokines. AB - Integrin heterodimers which share a common beta 1 subunit are the major cellular receptors for many extracellular matrix proteins. Here, we show that two inflammatory mediators, interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), can regulate the expression of the alpha 1 beta 1 integrin heterodimer, known to be a laminin and collagen receptor. In human skin fibroblasts 10 units/ml IL-1 beta increase the biosynthesis of the alpha 1 integrin subunit an average of 4.5-fold. Furthermore, IL-1 beta can turn on alpha 1 subunit expression in MG-63 human osteosarcoma cells even in conditions where the untreated MG-63 cells do not express it in detectable amounts. The effect of TNF-alpha on alpha 1 subunit expression is similar. Both IL-1 beta and TNF-alpha increased MG-63 cell adhesion on laminin. The effect of transforming growth factor-beta 1 (TGF-beta 1) on integrin expression in MG-63 cells has been previously described (Heino, J., and Massague, J. (1989) J. Biol. Chem. 264, 21806-21811). TGF-beta 1 decreases the biosynthesis of alpha 3 subunit but increases the production of alpha 2 subunit. IL-1 beta potentiates the effects of TGF-beta 1. Furthermore, in the presence of TGF-beta 1 the increase in the expression of alpha 1 subunit by IL-1 beta is even larger. Thus, IL-1 beta and TGF-beta 1, which usually have antagonistic functions in connective tissue, can regulate integrin expression in a synergistic way. PMID- 1744143 TI - Thromboxane A2 synthase. Modification during "suicide" inactivation. AB - Thromboxane synthase is a ferrihemoprotein which undergoes mechanism-based inactivation during catalysis. This "suicide" process may be an important factor for limiting thromboxane A2 biosynthesis in cells. Although the kinetics have been characterized for purified enzyme and platelets, the chemical basis for inactivation has remained unclear. Protein modification or alteration of the heme prosthetic group is each compatible with the irreversible nature of suicide inactivation of thromboxane synthase. We have investigated these two possibilities using enzyme purified to homogeneity. Our data show that the Soret absorbance spectrum of thromboxane synthase is unaltered by additions of prostaglandin endoperoxide H2 which cause enzymatic inactivation. Using a coupled cyclooxygenase/thromboxane synthase system and polyacrylamide gel electrophoresis we have demonstrated that the enzyme retains radiolabel under nondenaturing gel conditions. Label incorporation is reduced by the competitive thromboxane synthase inhibitor U63557, an agent that also protects the enzyme from inactivation. Under denaturing conditions the radiolabel localizes with the released heme prosthetic group. In addition, interaction of the heme prosthetic group with cyanide was prevented by inactivating the enzyme with prostaglandin H2. In similar experiments, the lipid hydroperoxide 15(S) hydroperoxyeicosatetraenoic acid inactivated thromboxane synthase with concurrent bleaching of the Soret spectrum. Labeling studies with a coupled soybean lipoxygenase/thromboxane synthase system indicate that, in this case, the apoenzyme is modified. These results suggest that the mechanism of thromboxane synthase inactivation during thromboxane A2 biosynthesis involves a tight, nondestructive association of substrate or product with the prosthetic heme group. Inactivation by hydroperoxides, however, appears to result from apoenzyme modification. These reactions may have important implications for cellular physiology and pathophysiology of thrombosis. PMID- 1744144 TI - A novel family of progesterone-induced, retinol-binding proteins from uterine secretions of the pig. PMID- 1744145 TI - Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble. PMID- 1744146 TI - Three-dimensional acceleration of the tibia during walking and running. AB - Measurements of tibial acceleration during walking and running were obtained by means of a triaxial accelerometer. The accelerometer was fixed to the free end of a Steinmann pin inserted into the right tibia of one volunteer subject. The patterns of tibial acceleration showed little step-to-step variation within each experimental condition. Following foot strike and depending upon footwear, the resultant tibial acceleration reached between 2.7 and 3.7 g during walking. The tibia experienced maximal accelerations of 10.6 g during running. The high values of tibial acceleration recorded in the antero-posterior (AP) and medio-lateral (ML) directions clearly revealed the importance of measuring all three components of acceleration to quantify the magnitude of the shock experienced by the lower limbs during locomotor activities. PMID- 1744147 TI - The free moment of ground reaction in distance running and its changes with pronation. AB - Many running injuries are successfully treated with footwear modifications designed to reduce pronation, but the underlying mechanism of treatment is not well understood. Previous attempts to correlate reduction in pronation with changes in ground reaction parameters have been unsuccessful. In this study, the free moment of ground reaction (Mz') was measured for 10 rearfoot strikers running at 4.5 m s-1 in each of three different pairs of running shoes designed to vary the extent of pronation during ground contact. Mz' patterns were highly variable between feet, but were repeatable within a given foot/footwear combination. Mz' was greatest in magnitude during the first half of support, when it acted in a direction resisting foot abduction, a component of pronation. It was opposite in sign and smaller in magnitude during the last 30% of support. The peak magnitude and the net angular impulse of Mz' were both increased significantly with increases in pronation. A net ground reaction moment was also calculated about a vertical axis fixed in the shoe, and was used in a first approximation model of the shoe/ground interface to predict when the foot is most likely to ab/adduct during running. In conclusion, this study characterized the Mz' pattern for a well-defined group of runners, and found that Mz' is sensitive to relatively large within-subject changes in pronation. PMID- 1744148 TI - A piece-wise non-linear elastic stress expression of human and pig coronary arteries tested in vitro. AB - Eight human and nineteen pig unembalmed proximal left anterior descending and circumflex coronary arteries were subjected to linear volume changes (2 s ramp time) at three fixed axial extensions while immersed in a physiological saline bath at body temperature. Measured parameters included: lumen pressure, outside diameter, axial force, and axial extension. The deformations were measured using a video dimensional analyzer. The arteries were inflated to pressures well above the physiological range at each axial extension. A latex inner tube was placed inside of each specimen to prevent leakage, and its effects upon the measured stresses were corrected analytically. With this method, the average circumferential and axial stresses could be computed directly from the experimental data. In both directions the average stresses measured displayed two distinct regions: stresses occurring for small diameter changes (physiological pressures) and stresses occurring for large diameter changes (high pressures). The resulting average small strain and large strain stress components were curve fit separately and, when reassembled, provided a piece-wise model of the stress response of coronary arteries over a wide range of inflation pressures and axial extensions. PMID- 1744149 TI - A microstructurally-based finite element model of the incised human cornea. AB - A mechanical model of the human cornea is proposed and employed in a finite element formulation for simulating the effects of surgical procedures, such as radial keratotomy, on the cornea. The model assumes that the structural behavior of the cornea is governed by the properties of the stroma. Arguments based on the microstructural organization and properties of the stroma lead to the conclusion that the human cornea exhibits flexural and shear rigidities which are negligible compared to its membrane rigidity. Accordingly, it is proposed that to a first approximation, the structural behavior of the cornea is that of a thick membrane shell. The tensile forces in the cornea are resisted by very fine collagen fibrils embedded in the ground substance of the stromal lamellae. When the collagen fibrils are cut, as in radial keratotomy, it is argued that they become relaxed since there is negligible transfer of load between adjacent fibrils due to the low shear modulus of the ground substance. The forces in the cornea are then resisted only by the remaining uncut fibrils. The cutting of fibrils induces an anisotropy and inhomogeneity in the membrane rigidity. By assuming a uniform angular distribution of stromal lamellae through the corneal thickness, geometric arguments lead to a quantitative representation for the anisotropy and inhomogeneity. All material behavior is assumed to be in the linear elastic regime and with no time-dependency. The resulting constitutive model for the incised cornea has been employed in a geometrically non-linear finite element membrane shell formulation for small strains with moderate rotations. A number of numerical examples are presented to illustrate the effectiveness of the proposed constitutive model and finite element formulation. The dependence of the outcome of radial keratotomy, measured in terms of the immediate postoperative shift in corneal power, on a number of important factors is investigated. These factors include the value of the elastic moduli of the stromal lamellae (dependent on the patient's age), the incision depth, the optic zone size, the number of incisions and their positions, and the intraocular pressure. Results have also been compared with expected surgical corrections predicted by three expert surgeons and show an excellent correspondence. PMID- 1744150 TI - Determination of biomechanical characteristics of restrictive adhesions and of functional impairment after flexor tendon surgery: a methodological study of rabbits. AB - Formation of restrictive adhesions is one of the main obstacles in rehabilitation following hand surgery. Most experimental work, however, involves only a macroscopic and/or histologic evaluation of the amount of adhesions, and their functional characteristics are poorly described. The aim of this study was to develop an experimental technique for characterization of the biomechanical properties of the finger-tendon unit. An instrument was developed for continuous and simultaneous recording of tensile load, tendon excursion and angular rotation in the distal interphalangeal joint of rabbit digits. Utilizing this instrument, it was revealed that the first 50 degrees of flexion required virtually no tensile load either in unoperated digits or immediately after tenorrhaphy. Thereafter, the load required to obtain further flexion was progressively increased. The strength of adhesions, determined 2 weeks after tenorrhaphy, was best expressed as the maximum tensile load recorded before 50 degrees of flexion was reached. This measurement could also be used to register the strength of the tendon repair and to detect partial tendon rupture during the measurement. The technique allows both adequate measurements of the strength of the adhesions and of the tendon gliding ability after flexor tendon surgery. PMID- 1744151 TI - A geometric theory of the equilibrium mechanics of fibers in ligaments and tendons. AB - This paper presents a theoretical analysis of the equilibrium mechanics of bending and twisting fiber geometries in ligaments and tendons. The theory predicts that the bending of loaded fibers is necessarily accompanied by large transverse pressures and pressure gradients. The predicted pressures are especially large at the bone tunnel entries of ligament grafts, where they can equal or exceed the applied tensile loads. Experimental measurements of internal pressures confirm these predictions. PMID- 1744152 TI - Thoracic injury potential of basic competition taekwondo kicks. AB - A major concern in competition taekwondo is the injury potential posed by many of the powerful kicks used. An investigation of the kinetics of four kicks frequently used in competition was performed with high speed video. Velocities were measured, and energy was calculated. Typical values for basic swing kicks were 15 ms-1 and 200 J. Basic thrust kicks possessed 45% less velocity but 28% more energy than swing kicks. Linkage models were developed to simulate the motion and kinetics of the kicking leg. Injury potential was evaluated through thoracic compression and viscous criterion models. These models predict a significant probability of serious injury with all kicks, with thoracic deflections from 3 to 5 cm and peak viscous tolerance values from 0.9-1.4 ms-1, when no protective body equipment is used. PMID- 1744153 TI - A novel approach to the distortion assessment of denture impression trays. AB - A novel method to treat and interpret distortion of denture impression trays has been proposed. When compared with the conventional method this approach, based on the general least squares principle, offers a significant advantage since the displacement for each individual point can be traced providing more profound insight into the character of the overall deformation itself. The method was applied to study dental impression trays manufactured of self-curing acrylic. The results indicate the existence of a large degree of individuality and non-uniform behaviour of a specific tray material. The method developed here can be applied to specimens of any arbitrary size and shape and it is not limited by the number of the reference points. PMID- 1744154 TI - On the estimation of joint kinematics during gait. AB - In gait analysis, the concepts of Euler and helical (screw) angles are used to define the three-dimensional relative joint angular motion of lower extremities. Reliable estimation of joint angular motion depends on the accurate definition and construction of embedded axes within each body segment. In this paper, using sensitivity analysis, we quantify the effects of uncertainties in the definition and construction of embedded axes on the estimation of joint angular motion during gait. Using representative hip and knee motion data from normal subjects and cerebral palsy patients, the flexion-extension axis is analytically perturbed +/- 15 degrees in 5 degrees steps from a reference position, and the joint angles are recomputed for both Euler and helical angle definitions. For the Euler model, hip and knee flexion angles are relatively unaffected while the ab/adduction and rotation angles are significantly affected throughout the gait cycle. An error of 15 degrees in the definition of flexion-extension axis gives rise to maximum errors of 8 and 12 degrees for the ab/adduction angle, and 10-15 degrees for the rotation angles at the hip and knee, respectively. Furthermore, the magnitude of errors in ab/adduction and rotation angles are a function of the flexion angle. The errors for the ab/adduction angles increase with increasing flexion angle and for the rotation angle, decrease with increasing flexion angle. In cerebral palsy patients with flexed knee pattern of gait, this will result in distorted estimation of ab/adduction and rotation. For the helical model, similar results are obtained for the helical angle and associated direction cosines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744155 TI - Skin carcinogenesis in man and in experimental animals. International Symposium. October 29-31, 1991, Heidelberg, Germany. Abstracts. PMID- 1744156 TI - Cancer of unknown primary site. PMID- 1744157 TI - Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: potential involvement of antiestrogenic mechanisms in vivo. AB - The N-methyl-N-nitrosourea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 micrograms/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 micrograms Mel/day or tamoxifen (20 micrograms/day). Thus, Mel appears to be an anti-promoting hormone that may antagonize the tumor promoting actions of estradiol in this model of mammary tumorigenesis. PMID- 1744158 TI - Tumorigenicity, invasion, and metastasis of human gastric cancer in nude mice. AB - Tumors derived from 105 patients with gastric cancer were subcutaneously heterotransplanted into nude mice in order to study their tumorigenicity and malignant behavior. Of the 105 gastric cancers, 45 were successfully transplanted (a 42.9% tumorigenesis rate). The tumorigenesis rate of Borrmann type 1 and 2 cancers (77.8%) was significantly higher than that of type 3 and 4 cancers (34.6%). Also, the tumorigenesis rate of differentiated carcinoma (57.1%) was significantly higher than that of undifferentiated carcinoma (30.9%). Spontaneous metastases from the subcutaneous tumors were observed in 5 of the 37 established tumor lines (13.5%), and macroscopic pulmonary metastases were common with one tumor line (SCK-29). Although most of the subcutaneous gastric cancers showed local expansion without distant metastasis, the same tumor cells implanted into the peritoneal cavity exhibited invasive growth and/or metastasis. Thus, the expression of a metastatic phenotype by human gastric cancer was influenced by the host microenvironment. The SCK-29 tumor line with its high metastatic potential may be useful for studies on the mechanism of blood-borne metastasis. PMID- 1744159 TI - Karyotypic change from heteroploidy to near diploidy associated with development of cisplatin resistance in a rat ovarian tumour cell line. AB - In a rat ovarian tumour cell line a 33-fold resistance to cisplatin (O-342/DDP) was developed in vitro by continuous exposure of the parental cell line (O-342) to stepwise increase cisplatin concentration in the culture medium. Both cell lines had a similar growth rate in vitro. Development of resistance was accompanied by a change of the karyotype from heteroploidy in chemosensitive O 342 cells to near diploidy in resistant O-342/DDP cells as shown by chromosome number distribution. This finding was confirmed by measuring cellular DNA content using flow-cytometry analysis. Flow karyotyping showed significant differences in chromosomal DNA contents between both cell lines. Our results suggest that the parent line O-342 consists of at least two subpopulations, a cisplatin-sensitive and a cisplatin-resistant one, corresponding to hyperploidy and near diploidy, respectively. Continuous cisplatin exposure of O-342 cells selectively killed the sensitive fraction, resulting in the karyotypic change observed. PMID- 1744160 TI - Influence of recombinant tumour necrosis factor alpha on blood flow and antibody localisation in human tumour xenografts in nude mice. AB - Mice with s.c. grafts of gastric carcinoma MKN45 or osteosarcoma 788T were injected i.v. with recombinant tumour necrosis factor alpha (rTNF alpha) and tumour blood flow rates were determined 4 h later as a fraction of the cardiac output g tissue-1. With MKN45, the tumour blood flow rate was significantly reduced from a mean of 1.86% cardiac output g-1 to 0.84% and 0.65% with 50 and 200 micrograms kg-1 rTNF alpha respectively. With 788T, the tumour blood flow rate was reduced at 50 micrograms kg-1 rTNF alpha from 1.13% cardiac output g-1 to 0.56%. There were essentially no changes in blood flow rates in other organs. The effect of rTNF alpha on localisation of monoclonal antibodies into these xenografts were examined. When a single dose of rTNF alpha (50 micrograms kg-1) was given at the same time as labelled NCRC-2 antibody there was a significant reduction in localisation into 788T osteosarcoma xenografts. In other tests, mice were injected daily for 3 days with 50 micrograms kg-1 rTNF alpha. They were injected i.v. with monoclonal antibody 4 h after the first injection and dissected on the 4th day. With 788T there was a small but not statistically significant reduction in the absolute amount of NCRC-2 antibody localising in tumour, although this reduction was greater when results were expressed as tumour to-blood ratios. With MKN45 xenografts, treatment with rTNF alpha had little effect on tumour localisation of an anti-(carcinoembryonic antigen) monoclonal antibody (NCRC-24). These studies show that TNF can be administered so as to reduce tumour blood flow and with little effect on tumour localisation of antibody, suggesting that combination therapy with TNF and antibodies or their immunoconjugates is feasible. Other studies have suggested that TNF can increase antibody localisation into tumours, but this was not seen here, and in some cases administration could reduce tumour localisation. It appears that this method of enhancing antibody localisation may be critically dependent on scheduling, and therefore it may not be extensively applicable. PMID- 1744161 TI - Prostatic atrophy in dogs after intravenous administration of a ureido ethylimidazoline derivative (CGP15'720A). AB - 1-(2-[4-Pridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxyphenyl)urea (CGP15'720A) is an experimental antineoplastic agent with marked activity against carcinogen induced lung tumors in Syrian hamsters and human lung tumor xenografts in nude mice. A preclinical toxicity study of this agent was carried out in mice and dogs which demonstrated the relatively nontoxic nature of the agent. In mice, single intraperitoneal dosage of 12 g/m2 did not produce lethality; however, lethality (30% of treated mice) was seen during treatment with 6 g/m2 daily for 5 days. No hematological, serum-chemistry or histopathological changes were detected in mice after single or five consecutive treatments with 12 g/m2. Dogs were treated with doses ranging from 5 g/m2 to 80 g/m2, with deaths occurring in a non-dose-related fashion after 10, 20, and 40 g/m2. Acute neurological toxicity after infusion was the dose-limiting toxicity in dogs. There were no consistent hematological or serum-chemistry aberrations in the treated dogs. The most consistent histopathological finding was prostatic atrophy, which was detected in 5/12 dogs in this series. PMID- 1744162 TI - Killing of Burkitt-lymphoma-derived Daudi cells by ultraviolet-inactivated vaccinia virus. AB - Interaction of active and UV-inactivated vaccinia virus at high multiplicity caused cytological changes and inhibition in cellular protein and DNA synthesis, thus arresting the multiplication of Burkitt-lymphoma-derived Daudi cells and eventually killing the cells. Adsorption to the cells but the lack of penetration was evident by immunofluorescence, electron microscopy and [3H]thymidine-labeled virus incorporation. Viral DNA synthesis or virus replication was not demonstrated. Thus, it appears that the massive adsorption of viral particles, active or UV-inactivated, or possibly a "toxic" component that resides in the virion, damages the plasma membrane and may be responsible for killing the cells by a mechanism of lysis from without. PMID- 1744163 TI - The heterogeneity of solid human xenotransplant tumours. AB - Fifteen xenograft tumour lines (4 osteosarcomas and 11 squamous carcinomas) were established on nude mice in numerous passages. Over a period of 4 years, samples were taken and studied systematically in more than 4000 histological slides. Of the tumour lines, 12 (4 osteosarcomas and 8 squamous carcinomas) showed remarkable dedifferentiation, but also redifferentiation towards a higher grade. There was a correlation between the rate of tumour takes in mice and poor prognosis in patients, but none between tumour doubling time and the phases of the cell cycle. Altogether, the results showed a great heterogeneity of human xenotransplants in terms of biological behaviour and morphological changes. PMID- 1744164 TI - Effects of an androgenic derivative on pre-established mammary tumours chemically induced in the rat. AB - The effects were studied of an androgenic derivative--danazol--administered at doses of 10-12 mg kg-1 day-1 during 97 days to rats with dimethylbenz[a] anthracene-induced mammary tumours. Our main observations were as follows. (a) Danazol did not influence ovarian function at the end of the assay. (b) The treatment with danazol reduced the incidence (P less than 0.05), number of tumours (P less than 0.05) and volume of malignant mammary tumours; on the other hand, the values of these parameters for benign tumours and those of doubtful expression were similar in both experimental groups. (c) Such differential action of Danazol seems to be due to the different incidence and/or content of receptors of both types of tumours. (d) The latter results lead to a hypothesis for the mechanism of action of danazol based on its behaviour at different levels. PMID- 1744165 TI - Production of interleukin-1 beta and tumour necrosis factor-alpha in patients with benign or malignant ovarian tumours. AB - To assess the role of interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) in the physiological host defence mechanisms against malignancies, the production of these cytokines in sera, ascitic and cyst fluids and in the tumour tissues of patients with benign or malignant ovarian tumours was studied. IL-1 beta was found neither in the sera nor in the ascitic fluids of these patients. It was also virtually absent from the cyst fluid samples. However, a mean value of 790 pg IL-1 beta/g tumour was found. Like IL-1 beta, TNF alpha was virtually absent in the serum samples. It was, however, detectable in the ascitic and cyst fluids and tumour tissues. The TNF alpha concentrations were highest in the tumour tissues, with a mean level of 328 pg/g tumour. When comparing the level of IL-1 beta and TNF alpha in patients with benign tumours to that seen in patients with malignant tumours, no differences in production were observed, regardless of the origin of the test samples. Our results indicate the production of IL-1 beta and TNF alpha in patients with ovarian tumours. More importantly, the finding that the production of these cytokines in patients with benign tumours is similar to that in patients with malignant tumours supports the conclusion that the production of these cytokines is more a nonspecific indicator of an inflammatory process than a specific response to a malignant process. PMID- 1744166 TI - Effects of radiation fractionation on four squamous cell carcinoma lines with dissimilar inherent radiation sensitivity. AB - The effect of radiation fractionation was investigated using a new 96-well-plate clonogenic assay in four squamous cell carcinoma lines. Earlier experiments had shown that two of the cell lines (UT-SCC-1A and UM-SCC-14A) were inherently relatively sensitive to irradiation, and two (UM-SCC-1 and UM-SCV-1A) relatively resistant. All of the four carcinomas from which the cell lines were established had poor clinical outcome. The radiation doses were given as a single exposure, or split into two or three equal fractions with a 24-h interval. The two inherently sensitive cell lines showed enhanced survival after radiation fractionation as compared with a single dose, whereas the resistant cell lines did not. The result suggests that both the inherent resistance of cancer cells to irradiation and the repair of sublethal radiation damage may lead to treatment failure, and that shortening of the total irradiation time may overcome cancer cell recovery between fractions in some, but not in all carcinomas. PMID- 1744167 TI - Histological and immunohistochemical findings of prostatic carcinoma after external or interstitial radiotherapy. AB - In a retrospective study, the extent of reactions of different types of prostatic carcinomas to external or interstitial radiotherapy was compared with reactions to hormonal therapy. It is shown that prostatic carcinomas of different grades of differentiation can be divided into two main subgroups with distinctly different survival rates; i.e., prostatic carcinomas grades of malignancy Ib/IIa and grades IIb/III. Within an observation time of 10 years, the prostatic carcinoma grade of malignancy Ib/IIa shows a good response to external and interstitial radiotherapy. None of the patients died of the prostatic carcinoma. In the more poorly differentiated prostatic carcinomas, 2 out of 11 patients with external radiotherapy died of the carcinoma. The death rates from disease after hormonal therapy were higher, and the survival times were very short without therapy. Regressive changes are much more distinctly expressed in the better differentiated carcinoma group. Differential diagnostic difficulties between regressive changes in carcinomatous glands and normal glands could be resolved by immunohistochemical proof of high-molecular-mass cytokeratin in basal cells. PMID- 1744168 TI - The role of insulin-related substance in Hodgkin's disease. AB - An insulin-related growth-promoting substance was detected in the serum of a patient with Hodgkin's disease who suffered from severe hypoglycaemia, as well as in the supernatant of homogenized spleen tissue of the same patient. Low concentrations of this substance enhanced DNA synthesis of short-term-cultured spleen tumour cells obtained from the same patient, while the addition of anti insulin antiserum interfered with that effect. Moreover, the preincubation of this insulin-related substance with the anti-insulin antiserum abrogated its stimulatory effect on tumour cell proliferation. Both insulin and the insulin related substance bound to patients splenocytes to a similar extent. The data suggest that the insulin-related substance, found in this particular case of Hodgkin's disease, plays a role in tumour progression by an autocrine mechanism. PMID- 1744169 TI - Hydrogen peroxide-induced oxidative stress to the mammalian heart-muscle cell (cardiomyocyte): lethal peroxidative membrane injury. AB - Oxidative stress induced by hydrogen peroxide (H2O2) may contribute to the pathogenesis of ischemic-reperfusion injury in the heart. For the purpose of investigating directly the injury potential of H2O2 on heart muscle, a cellular model of H2O2-induced myocardial oxidative stress was developed. This model employed primary monolayer cultures of intact, beating neonatal-rat cardiomyocytes and discrete concentrations of reagent H2O2 in defined, supplement free culture medium. Cardiomyocytes challenged with H2O2 readily metabolized it such that the culture content of H2O2 diminished over time, but was not depleted. The consequent H2O2-induced oxidative stress caused lethal sarcolemmal disruption (as measured by lactate dehydrogenase release), and cardiomyocyte integrity could be preserved by catalase. During oxidative stress, a spectrum of cellular derangements developed, including membrane phospholipid peroxidation, thiol oxidation, consumption of the major chain-breaking membrane antiperoxidant (alpha tocopherol), and ATP loss. No net change in the protein or phospholipid contents of cardiomyocyte membranes accompanied H2O2-induced oxidative stress, but an increased turnover of these membrane constituents occurred in response to H2O2. Development of lethal cardiomyocyte injury during H2O2-induced oxidative stress did not require the presence of H2O2 itself; a brief "pulse" exposure of the cardiomyocytes to H2O2 was sufficient to incite the pathogenic mechanism leading to cell disruption. Cardiomyocyte disruption was dependent upon an intracellular source of redox-active iron and the iron-dependent transformation of internalized H2O2 into products (e.g., the hydroxyl radical) capable of initiating lipid peroxidation, since iron chelators and hydroxyl-radical scavengers were cytoprotective. The accelerated turnover of cardiomyocyte-membrane protein and phospholipid was inhibited by antiperoxidants, suggesting that the turnover reflected molecular repair of oxidized membrane constitutents. Likewise, the consumption of alpha-tocopherol and the oxidation of cellular thiols appeared to be epiphenomena of peroxidation. Antiperoxidant interventions coordinately abolished both H2O2-induced lipid peroxidation and sarcolemmal disruption, demonstrating that an intimate pathogenic relationship exists between sarcolemmal peroxidation and lethal compromise of cardiomyocyte integrity in response to H2O2 induced oxidative stress. Although sarcolemmal peroxidation was causally related to cardiomyocyte disruption during H2O2-induced oxidative stress, a nonperoxidative route of H2O2 cytotoxicity was also identified, which was expressed in the complete absence of cardiomyocyte-membrane peroxidation. The latter mode of H2O2-induced cardiomyocyte injury involved ATP loss such that membrane peroxidation and cardiomyocyte disruption on the one hand and cellular de-energization on the other could be completely dissociated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744170 TI - Calcium transport by sarcoplasmic reticulum of vascular smooth muscle: I. MgATP dependent and MgATP-independent calcium uptake. AB - The components of 45calcium (Ca) uptake were studied in saponin skinned rat caudal artery. The steady-state Ca content increased when the free Ca concentration was varied from 10(-8) to 10(-4) M but was reduced by azide when the free Ca concentration exceeded 3.1 microM. The azide sensitivity and low affinity for Ca were consistent with functional mitochondria. The azide insensitive component consisted of a small bound and a larger releasable Ca fraction. After skinning in Triton X-100, approximately 4 mumol Ca/kg wet tissue remained, which represented a tightly bound but slowly exchangeable Ca pool. The Ca content was independent of the free Ca concentration and MgATP, and it was not released with A-23187 or Ca. The Ca content of the larger fraction was a higher order function of the free Ca concentration and was released with A-23187, indicating it resided within a membrane-bounded structure. Ca uptake by the releasable fraction was increased by oxalate, MgATP, phosphocreatine, temperature, phosphate, and ruthenium red and represents Ca sequestered by the sarcoplasmic reticulum (SR) with little contribution from other Ca binding or storage sites. It is described by the coefficients Umax = 96.94 mumol/kg wet tissue, K1/2 = 0.75 microM, and Hill coefficient = 1.70. The SR in this preparation regulates cytosolic Ca concentrations under physiological conditions and can accumulate Ca by MgATP-dependent and MgATP-independent process. The larger, MgATP-dependent Ca uptake is described by the coefficients Umax = 72.87 mumol/kg wet tissue, K1/2 = 0.8 microM, and Hill coefficient = 2.09 and is consistent with Ca sequestered by the Ca-transport ATPase of smooth muscle SR. The smaller, MgATP-independent uptake is described by the coefficients Umax = 24.14 mumol/kg wet tissue, K1/2 = 0.56 microM, and Hill coefficient = 1.01 and represents Ca sequestered by an unidentified mechanism or by a subpopulation of SR. PMID- 1744171 TI - Inhibition of protein synthesis and heat protection: histidinol-resistant mutant cell lines. AB - The mechanism of histidinol (HST)-induced heat protection was investigated to test the hypothesis that the cessation of protein synthesis itself is one of the events involved in heat protection. For this study, we isolated three HST resistant mutant strains. HST (5 mM), which inhibited protein synthesis by 88% in the wild type, caused only 0, 9, and 25% inhibition in three mutants, respectively. The drug, which afforded heat protection, (i.e., a 125-fold increase in survival from 4 x 10(-3) to 5 x 10(-1) after 2 hr at 43 degrees C in wild type), did not protect mutant cells from heat killing. In contrast, cycloheximide (10 micrograms/ml) which inhibited protein synthesis by 95% in both wild type and mutant cell types, protected both cell types from heat killing. Therefore, these results suggest that the cessation of protein synthesis, per se, preventing synthesis of nascent polypeptides, is a major event leading to heat protection. PMID- 1744172 TI - Stimulation of large proteoglycan synthesis in cultured smooth muscle cells from pig aorta by endothelial cell-conditioned medium. AB - We have previously shown (Berrou et al., J. Cell. Phys., 137:430-438, 1988) that porcine endothelial cell-conditioned medium (ECCM) stimulates proteoglycan synthesis by smooth muscle cells from pig aorta. ECCM stimulation requires protein cores for glycosaminoglycan chain initiation and is accompanied by an increase in the hydrodynamic size of proteoglycans secreted into the medium. This work investigates the mechanisms involved in the ECCM effect. 1) Control and ECCM stimulated proteoglycan synthesis (measured by a 20 min [35S]-sulfate labeling assay) was not inhibited by cycloheximide, indicating that the proteoglycans were composed of preexisting protein cores and that ECCM stimulates glycosylation of these protein cores. 2) Whereas ECCM stimulation of [35S]-methionine incorporation into secreted proteins only occurred after a 6 h incubation, the increase in [35S] methionine-labeled proteoglycans was observed after 1 h, and the increase was stable for at least 16 h. 3) As analysed by electrophoresis in SDS, chondroitinase digestion generated from [14C] serine-labeled proteoglycans 7 protein cores of high apparent molecular mass (550-200 kDa) and one of 47 kDa. The two protein cores of highest apparent molecular masses (550 and 460 kDa), but not the 47 kDa protein cores, showed increased [14C]-serine incorporation in response to ECCM (51%, as measured by Sepharose CL-6B chromatography). 4) Finally, incorporation of [35S]-sulfate into chondroitinase-generated glycosaminoglycan linkage stubs on protein cores was determined by Sepharose CL 6B chromatography: ECCM did not modify the ratio [35S]/[14C] in stimulated protein cores, indicating that ECCM did not affect the number of glycosaminoglycan chains. The results of these studies reveal that 1) endothelial cells secrete factor(s) that preferentially stimulate synthesis of the largest smooth muscle cell proteoglycans without structural modifications and 2) the stimulation proceeds via increased glycosylation of protein core through enhancement of xylosylated protein core, followed by enhanced protein synthesis. PMID- 1744173 TI - Sheep amniotic fluid has a protein factor which stimulates human fibroblast populated collagen lattice contraction. AB - Sutured incisional wounds made in fetal sheep and rabbits heal without scarring. Fetal sheep excisional wounds can close by contraction, but those in fetal rabbits do not. In vivo and in vitro evidence suggests that rabbit amniotic fluid inhibits wound contraction. The question arises: does sheep amniotic fluid promote wound contraction because their fetal wounds close by contraction? Sheep amniotic fluid (SAF) from 100 and 125 days gestation was tested in fibroblast populated collagen lattice (FPCL) system, an in vitro model of wound contraction. SAF stimulated FPCL contraction in a dose responsive manner. SAF from a 100 day fetus was more stimulating than a 125 day SAF. SAF enhanced FPCL contraction in the presence or absence of serum. SAF was fractionated by size, using column chromatography. It yielded a fraction with an estimated molecular weigh near 40,000 daltons, which stimulated FPCL contraction. The factor was inactivated by proteolytic digestion and heat denaturation. This protein fraction which stimulates FPCL contraction is not related to 1) actin-myosin filaments enhanced contraction by ATP-induced cell contraction, 2) promotion of fibroblast elongation on glass surface or in collagen, or 3) increased cell number by enhanced fibroblast duplication in a collagen matrix. A mechanism for SAF promotion of FPCL contraction was investigated but not identified. PMID- 1744174 TI - Characterization of spleen colonies derived from mice with mutations at the W locus. AB - Mice with mutations at the W locus have a hemopoietic stem cell defect characterized by an apparent deficiency of spleen colony forming cells (CFU-S). In the present report, we provide evidence that mutant cells form colonies and we compare the characteristics of the colonies derived from mutant and normal cells. To perform the colony-derivation studies, marrow cells were transferred into lethally irradiated congenic hosts that differed from the donors in the ubiquitous genetic marker, glucose phosphate isomerase (GPI-1). Donor GPI-1 comprised over 50% of the marker in the host spleen and marrow by 12 days post injection, regardless of whether the donor was mutant or normal. To characterize the colonies, serially sectioned host spleens were examined microscopically. Colonies are present by 8 days post-transplantation regardless of donor genotype, but mutant colonies are distinctly different from normal colonies. The proportion of blast and granulocyte colonies is always greater in W/Wv than in +/+ recipients. Unlike the W/Wv donors, the +/+ donors generate primarily erythrocyte colonies at 8, 10, and 14 days and mixed colonies at 12 days post-injection. Colonies from the mutant mice are generally smaller but visible colonies do appear by 12 days. The results are consistent with the notion that the anemia in W/Wv mice is caused by the early restriction of differentiating cells to a non erythrocyte lineage accompanied by the delayed amplification of mutant hemopoietic cells. Whether this means erythrocyte-committed cells are absent or are present but unable to respond to the appropriate cytokines is not possible to determine from the current experiments. PMID- 1744175 TI - Depolarization of the membrane potential decreases the ATP-induced influx of extracellular Ca2+ and the refilling of intracellular Ca2+ stores in rat thyroid FRTL-5 cells. AB - The aim of the present study was to investigate the effect of membrane depolarization on ATP-induced changes in intracellular Ca2+ ([Ca2+]i) and the refilling of intracellular Ca2+ stores in thyroid follicular FRTL-5 cells. Depolarizing the cells with 50 mM K+, an amount sufficient to almost totally depolarize the cells as determined by bisoxonal, significantly reduced the ATP induced uptake of 45Ca2+. This effect was not dependent on an enhanced efflux of Ca2+, as no difference in the ATP-induced efflux of 45Ca2+ was obtained between control cells and depolarized cells. The ATP-induced transient increase in [Ca2+]i in Fura-2 loaded cells was not altered by depolarization, whereas the ATP induced plateau in [Ca2+]i was decreased compared with control cells. Furthermore, in cells stimulated with ATP in a Ca(2+)-free buffer, readdition of Ca2+ after the termination of the ATP response induced a decreased response in [Ca2+]i in depolarized cells. Refilling of intracellular Ca2+ stores was investigated by first stimulating the cells with noradrenaline (NA). The effect of NA was then terminated with prazosin, and the cells restimulated with ATP. In cells depolarized with high K+, the response to ATP was decreased compared with that seen in control cells. The results thus suggest that both the ATP-induced influx of extracellular Ca2+ and the refilling of intracellular Ca2+ stores is decreased in depolarized FRTL-5 cells. PMID- 1744176 TI - Na+/K+/Cl- cotransport is stimulated by a Ca(++)-calmodulin-mediated pathway in BALB/c 3T3 fibroblasts. AB - In the present study, we investigated the role of intracellular Ca++ in the stimulation of the Na+/K+/Cl- cotransport in synchronized BALB/c 3T3 cells. The Na+/K+/Cl- cotransport was stimulated by the growth factors EGF, TGF-alpha, IGF 1, and IGF-2, which do not activate protein kinase C, but do induce a transient increase in free cytoplasmic Ca++. In addition, direct activation of protein kinase C by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) did not affect the Na+/K+/Cl- cotransport activity of quiescent cells. The Na+/K+/Cl- cotransport was also stimulated by the above mitogens in cells pretreated with the phorbol ester TPA. This treatment led to a progressive decline in the activity of cellular protein kinase C. This result implies that cells deficient in protein kinase C may still support stimulation of the Na+/K+/Cl- cotransport. Taken as a whole, these findings suggest that the Na+/K+/Cl- cotransport is stimulated predominantly by a protein kinase C-independent mechanism in BALB/c 3T3 fibroblasts. Both the intracellular Ca++ antagonist 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) and two potent calmodulin antagonists, trifluoperazine (TFP) and chloropromazine (CP), blocked serum- and mitogen stimulated Na+/K+/Cl- cotransport. These results suggest that the Na+/K+/Cl- cotransport is stimulated by an increase of intracellular Ca++ and subsequently by a Ca(++)-calmodulin-mediated pathway in the synchronized BALB/c 3T3 fibroblasts. PMID- 1744177 TI - Desmin is present in proliferating rat muscle satellite cells but not in bovine muscle satellite cells. AB - The presence of desmin was characterized in cultured rat and bovine satellite cells and its potential usefulness as a marker for identifying satellite cells in vitro was evaluated. In primary cultures, positive immunohistochemical staining for desmin and skeletal muscle myosin was observed in rat and bovine myotubes. A small number of mononucleated cells (20% of rat satellite cells and 5% of bovine satellite cells) were myosin-positive, indicative of post-mitotic differentiated myocytes. In bovine satellite cell cultures 13% of the mononucleated cells were desmin-positive, while 84% of the mononucleated cells in rat satellite cell cultures were desmin-positive. Rat satellite cell mass cultures and bovine satellite cell clonal density cultures were pulsed with 3H-thymidine, and autoradiographic data revealed that greater than 94% of dividing rat cells were desmin-positive, suggesting that desmin is synthesized in proliferating rat satellite cells. However, no desmin was seen in cells that incorporated labeled thymidine in bovine satellite cell clones. Analysis of clonal density cultures revealed that only 14% of the mononucleated cells in bovine satellite cell colonies were desmin-positive, whereas 98% of the cells in rat satellite cell colonies were desmin-positive. Fibroblast colonies from both species were desmin negative. In order to further examine the relationship between satellite cell differentiation and desmin expression, 5-bromo-2'-deoxyuridine (BrdU) was added to culture medium at the time of plating to inhibit differentiation. Fusion was inhibited in rat and bovine cultures, and cells continued to divide. Very few desmin-positive cells were found in bovine cultures, but greater than 90% of the cells in rat cultures stained positive for desmin. The presence of desmin and sarcomeric myosin was also evaluated in regenerating rat tibialis anterior five days after bupivacaine injection. In regenerating areas of the muscle many desmin positive cells were present, and only a few cells stained positive for skeletal muscle myosin. Application of desmin staining to rat satellite cell growth assays indicated that rat satellite cells cultured in serum-containing medium were contaminated with fibroblasts at levels that ranged from approximately 5% in 24 hr cultures to 15% in mature cultures. In defined medium 4 day cultures contain approximately 95% to 98% desmin-positive satellite cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744178 TI - Germ cell mitogenic activity is associated with nerve growth factor-like protein(s). AB - The mitogenicity of germ cell proteins released from round spermatids (RS) and pachytene spermatocytes (PS) was investigated. Germ cells were isolated by centrifugal elutriation from 90-day-old rat testes and incubated in a supplement enriched culture media that lacked exogenous proteins. The conditioned culture media of RS and PS were dialysed/concentrated and lyophilized to prepare RS protein (RSP) and PS protein (PSP). Mitogenic activity of RSP and PSP was determined by 3H-thymidine incorporation into Swiss 3T3 fibroblasts. RSP and PSP stimulated 3H-thymidine incorporation by fibroblasts in a dose-dependent manner. At a higher concentration of RSP (300 micrograms/ml), fibroblast proliferation was stimulated from 6- to 20-fold of control cultures, whereas PSP (300 micrograms/ml) stimulated fibroblast proliferation 2.5-fold of control cultures. Since RSP exhibited substantially greater mitogenic activity than PSP we further investigated the RSP mitogenic substance(s) by immunoneutralization with antibodies against several growth factors. The mitogenic activity of RSP was significantly reduced by treatment with nerve growth factor (NGF) antibody, while neither the treatment of RSP with acidic fibroblast growth factor (aFGF) antibody, nor basic fibroblast growth factor (bFGF) antibody significantly modified the mitogenic activity of RSP. Interestingly, murine NGF-beta, recombinant human NGF-beta, and bovine serum albumin (BSA) did not exhibit mitogenic activity on 3T3 fibroblasts. Nevertheless, the presence of a NGF-like protein in RS and PS was confirmed by indirect immunofluorescence staining with a murine NGF antibody. Subsequently, a Western blot analysis with the NGF antibody identified two immunoreactive bands of 41 +/- 2 kDa and 51 +/- 1 kDa in both RSP and PSP under reduced conditions. These germ cell NGF-like proteins were apparently different from similarly prepared murine and human NGFs (13 kDa) in their molecular weight. Furthermore, neurite outgrowth from pheochromocytoma cells (PC-12), a functional bioassay for NGF-like activity, was stimulated by addition of RSP and PSP to the culture media of the PC-12 cells. These results demonstrate mitogenic activity in germ cell proteins (RSP and PSP) and identify a NGF-like protein(s) which is associated with most of this activity. PMID- 1744179 TI - The effects of chronic exposure to supraphysiological concentrations of 3, 5, 3' triiodo-L-thyronine (T3) on cultured GC cells. AB - We have characterized the effects of supraphysiological concentrations of T3 on GC cells, a cultured cell line in which physiologic concentrations of T3 regulate cell growth, protein content, and growth hormone (GH) production. GC cells were exposed to 3 times (1.0 nM) and 80 times (25.0 nM) the physiologic concentration of T3 (0.3 nM) for either 4 d or for greater than 3 months. Both short and prolonged exposure to supranormal T3 concentrations supported maximal cell growth rate and induced significant increases in total protein (P less than 0.025) and GH production (P less than 0.01) per cell when compared to measurements in control GC cells. In addition, exposure to 1.0 nM and 25.0 nM T3 for greater than 3 months enhanced the toxicity of heat shock in a manner similar to previously described effects on GC cells due to T3 exposure of shorter duration. Thus, initial responses to raised T3 concentrations in cultured GC cells persisted without alteration when hormone exposure was prolonged for greater than 3 months. PMID- 1744180 TI - Cell cycle dependent alterations of chromatin structure in situ as revealed by the accessibility of the nuclear protein AF-2 to monoclonal antibodies. AB - We have recently described a novel nuclear antigen, AF-2, which is related to cell cycle dependent alterations of chromatin structure. We show by two parameter flow cytometry on a cell by cell basis that the antigen is accessible to specific monoclonal antibodies only in mitotic and postmitotic early G1-phase cells. The evaluation of nuclease susceptibility and AF-2 antigen accessibility reveals different subcompartments of the G1-phase of the cell cycle with distinct chromatin conformations. Digestion with DNase I seems to alter the chromatin structure according to concentration and this is reflected by an increase of the antigen accessibility. Chromatin in the more condensed early G1-phase is specifically digested by lower concentrations of the enzyme than chromatin in later stages of interphase. Chromatin from cells in the late-G1, S-, and G2 phases shows a higher relative resistance to DNase I and a reduced accessibility of the AF-2 antigen to monoclonal antibodies. Nuclease S1 has a similar effect on chromatin topology, as revealed by the reaction with anti-AF-2 antibodies, without digestion of detectable amounts of DNA. The antigen becomes available to the antibodies in almost all cells by digestion with high concentrations of DNase I or Nuclease S1. PMID- 1744181 TI - Lectin binding to gp60 decreases specific albumin binding and transport in pulmonary artery endothelial monolayers. AB - The effect of albumin binding to cultured bovine pulmonary artery endothelial cell (BPAEC) monolayers on the transendothelial flux of 125I-labelled bovine serum albumin (BSA) was examined to determine its possible role on albumin transcytosis. The transport of 125I-BSA tracer across BPAEC grown on gelatin- and fibronectin-coated filters (0.8 microns pore diam.) was affected by the presence of unlabelled BSA in the medium in that transendothelial 125I-BSA permeability decreased, reaching a 40% reduction at BSA concentrations equal to or greater than 5 mg/ml. BSA binding to BPAEC monolayers was saturated at concentration of 10 mg/ml with an apparent binding affinity of 6 x 10(-7) M. In contrast, gelatin added to the medium altered neither 125I-BSA binding nor transport. Several lectins were tested for their ability to inhibit 125I-BSA binding and transport. One lectin, Ricinus communis (RCA), reduced 125I-BSA binding by 70% and transport by 40%. Other lectins, Ulex europaeus, Triticum vulgare, and Glycine max decreased neither 125I-BSA binding nor transport. The reduction of 125I-BSA transport by RCA was not observed in the presence of saturating levels of BSA, indicating that RCA influenced only the albumin-dependent component of transport. RCA, but not other lectins, precipitated a 60 kDa plasmalemmal glycoprotein from cell lysates of surface radioiodinated BPAEC monolayers. This 60 kDa glycoprotein appears to be the equivalent of gp60 identified previously as an albumin binding glycoprotein in rat microvascular endothelium. In summary, approximately 40% of albumin transport across BPAEC monolayers is dependent on albumin binding. This component of albumin transport is inhibited by 80% by the binding of RCA to gp60. These results suggest that binding of albumin to gp60 on pulmonary artery endothelial cell membrane is a critical determinant of transendothelial albumin flux involving mechanisms such as plasmalemmal vesicular transcytosis. PMID- 1744182 TI - Group B streptococcus infection in mother and child. AB - Despite significant advances in obstetric and pediatric health care, group B beta hemolytic Streptococcus (GBS) remains one of the most prevalent and devastating pathogens in peripartum women and their newborn infants. It may cause urinary tract infection, chorioamnionitis and endometritis, bacteremia, and cesarean wound infection in the peripartum period. Moreover, GBS accounts for nearly 50% of serious neonatal bacterial infections. Approximately three in every 1,000 children born in the United States acquire pneumonia, sepsis, or meningitis from GBS, with combined mortality and morbidity exceeding 50% despite appropriate antibiotic and supportive therapy. Estimates indicate that more than 10,000 infants are affected annually, at a cost of more than $300 million. Neonatal disease is divided into early- and late-onset syndromes: The illness emerging after six days of age differs in terms of GBS serotype, clinical manifestations, and outcome from the disseminated process seen in earlier onset. We describe two infants infected with GBS and discuss risk factors, pathogenesis, diagnosis, therapy, and options for disease prevention in the peripartum woman and her infant. PMID- 1744183 TI - Planetary protection. PMID- 1744184 TI - Into the heart. PMID- 1744185 TI - Beta-blocker overdose in an LPN. PMID- 1744186 TI - An unusual cause of fever in a newborn infant. PMID- 1744187 TI - Contractile protein alterations in heart failure. AB - After nearly three decades of intense investigation, the precise cellular mechanisms underlying impaired contractility in heart failure remain to be defined. Nevertheless, growing use of the tools of molecular biology promises new insights into how alterations of contractile proteins mediate the functional derangements of failure. PMID- 1744188 TI - Adenocarcinoma of the liver without a detectable primary. PMID- 1744189 TI - Syndromes derived from the Child Behavior Checklist for clinically referred Israeli boys aged 6-11: a research note. AB - Child Behavior Checklists (CBCL) were completed by parents of 450 clinically referred Israeli boys aged 6-11. Principal components analyses with varimax rotation yielded 10 syndromes: aggressive, uncommunicative/social withdrawal, depressed, delinquent, hyperactive, somatic complaints, anxious, immature, unpopular, and odd. The first seven syndromes were highly correlated with American and Dutch syndromes derived from the CBCL providing further evidence of their cross-cultural robustness. PMID- 1744190 TI - Child behaviours as stressors: replicating and extending the use of the CARS as a measure of stress: a research note. AB - Autistic children represent a source of stress for their parents, but the most appropriate way to measure this stress is not clear. Two studies in the literature compared parents' and professionals' ratings of symptom severity, and had parents rate the stressfulness of each symptom. The present study sought to replicate past research, and to extend it by validating this method of measuring parental stress compared to more traditional measures. Results indicated that mothers, fathers, and professionals agreed on the severity of child behaviours. Mothers found these behaviours significantly more stressful than fathers. The stress related to specific child behaviours was significantly correlated with more general measures of parental stress. PMID- 1744191 TI - Debate and argument. Concordance for the syndrome of autism. PMID- 1744192 TI - Annotation: growing up as a twin: twin-singleton differences in psychological development. PMID- 1744193 TI - IQ and the genetics of autism. AB - While there seems to be general agreement that genetic factors play some role in the etiology of autism, many important questions remain unresolved. The purpose of this paper is to review five issues with respect to the association between low IQ and autism from a familial-genetic viewpoint: (1) does IQ estimate the severity of the autistic genotype?; (2) what is the relationship between probands' and sibs' IQs?; (3) what is the relationship between parents' and probands' IQs?; (4) why do females with autism have lower IQs than males with the disorder?; and (5) does IQ vary with the cause of autism? With respect to each issue, possible resolutions are outlined, as are the implications for understanding the genetic mode of transmission. The review concludes with a possible model for the genetic etiology of autism. PMID- 1744194 TI - A comparison of ICD-9 and ICD-10 diagnoses of child and adolescent psychiatric disorders. AB - ICD-9 and ICD-10 categories were compared in a consecutive cohort of patients attending a public child and adolescent psychiatric service. There were some remarkable changes in the frequency of comparable diagnoses that reflect both systematic effects due to the changed format of the ICD-10 as well as certain changes specific to the service. PMID- 1744195 TI - The inter-rater reliability of child and adolescent psychiatric disorders in the ICD-10. AB - Using the ICD-10 criteria for mental and behavioral disorders, a series of five written case-histories was rated by 32 clinicians with various training backgrounds and different degrees of clinical expertise. As expected, reliability was dependent on clinical expertise and increased when an option for an alternative diagnosis was provided in addition to the main diagnosis. Inter-rater agreement in 10 written case-histories rated by senior child and adolescent psychiatrists was to 66%. In comparison with previous studies based on the ICD-9, there is some evidence that the improved conceptualization of the ICD-10 contributes to better reliability. PMID- 1744196 TI - The transition to adolescence: the role of gender and stress in problem behavior and competence. AB - The differential change of boys and girls across pre-adolescence, early adolescence, and middle adolescence was examined. The participants were 259 children, their mothers, and their social studies teachers. The children completed a measure of internalizing problems and adults completed measures of the child's externalizing and internalizing problems and competence. Relative to girls, boys had more problems and less competence at pre-adolescence and/or less problems and more competence by mid-adolescence. A stressor, parental divorce, did not exacerbate the gender by developmental age period interaction. The differential vulnerability of boys and girls at different developmental periods is considered. PMID- 1744197 TI - Familial adversities and child psychiatric disorders. AB - The well known association between child and adolescent psychiatric disorders and chronic adversities was proved in a field sample. Children (356) were investigated at the ages of 8 and 13 years. The association between child psychiatric disorders and chronic adverse conditions in the familial environment- measured by the FAI--was analysed with respect to the variables: age, sex, psychiatric diagnoses, and course (stability) of disorder. The FAI proved to be predictive of psychiatric disorder, in particular of early onset disorder, of disorders in boys, and of conduct disorders. According to the results, the common assumption that chronic adversities cause child psychiatric disorders must be viewed cautiously. PMID- 1744198 TI - Infant crying patterns in the first year: normal community and clinical findings. AB - To provide information about persistent infant crying, crying durations and patterns were measured at four age points (1-3, 4-6, 7-9 and 10-12 months) in normal community (N = 400) and clinical (N = 68) samples. The findings provide a range of prevalence figures and descriptive statistics which may be useful for parents and professionals faced with infant crying. A large developmental shift in crying amount, and two age-related changes of crying pattern, were found. Clinical infants showed the same crying profiles as the general community infants, but were found to cry substantially more. Although mothers of first borns were more likely to seek clinical referral, there were no birth-order differences in crying amount or pattern. The findings' implications for studies of infant temperament and development are indicated. PMID- 1744199 TI - A reassessment of the role of ethnicity in children's social perception. AB - This study examines the salience of ethnicity in 8- and 11-year-old children's social categorizations and preference judgements. Unlike previous research, children were afforded the possibility of responding to photographs of target persons on the basis of either individual characteristics (expressed affect) or group characteristics (ethnicity and gender), and it was found that ethnicity was seldom used as a basis for categorizing persons, nor was it widely implicated in judgements of preference. Since this study was conducted in an area virtually devoid of ethnic minority groups, a replication was undertaken in an inner city area of London. Apart from the finding that ethnicity appeared to be a fairly salient basis for categorization amongst the 8-year-old children, results essentially similar to those of the first study were obtained. Implications of the data for children's social perception are discussed. PMID- 1744200 TI - Localization of visual targets inside and outside the field of view: the effect of hearing loss. AB - In two experiments the eye and head localization responses of auditorially handicapped children to visual targets in a surrounding circular display were compared with the corresponding responses of age-matched controls (Experiment 1, mean age: 131 months, hearing loss of auditorially handicapped children greater than 90 dB; Experiment 2, two age groups with mean ages: 72 and 123 months, hearing loss of auditorially handicapped greater than 50 dB). It was hypothesized that an auditory deprivation results in a deficient spatial orientation to the regions outside the visual field. This in turn should affect the actual localization behaviour to visual targets situated within those regions. Differences between the auditorially handicapped and non-handicapped children were found with respect to the localization times of so-called 'reversal' responses of eye (Experiment 1) and head (Experiment 2) to targets situated outside the field of view. In the second experiment significant age-effects were present. The implications of these findings for the presence of specific differences in cognitive spatial abilities between auditorially handicapped and hearing children are discussed. PMID- 1744201 TI - Differences in the structure of social behaviour of autistic children and non autistic retarded controls. AB - Social and task-oriented behaviours of autistic children were compared to those of individually age- and IQ-matched non-autistic retarded controls. Autistic children showed deficits in visual reciprocity, in indicating joint attention and referential head gestures, and in the integration of gaze and gestures when reacting to tasks. The findings confirmed the notion of social and pragmatic communicative deficits in autism. The implications of these findings for theories of social behaviour in autism (avoidance, facial perception, theory of mind) are discussed. PMID- 1744202 TI - Characterization of a tryptic digest by high-performance displacement chromatography and mass spectrometry. AB - High-performance displacement chromatography (HPDC) provides a means of increasing the capacity of a chromatographic column, while maintaining the resolution afforded by high-performance liquid chromatographic (HPLC) instruments. The high capacity and high resolution of HPDC can be exploited in tryptic mapping to facilitate the characterization of a protein preparation. In this manner, minor constituents of the mixture, which may be difficult to isolate by conventional chromatographic methods, can be obtained in sufficient amounts to permit chemical characterization by established techniques. The isolation by HPDC of peptides obtained by digestion of recombinant human growth hormone (rhGH) and the subsequent characterization of the peptides are described. The identification of certain of these peptides revealed information on the specificity of trypsin for the substrate, rhGH, and for autolysis. Fractions from the HPDC tryptic map were collected and analyzed by electrospray ionization mass spectrometry (ESI-MS) either directly or following further separation by gradient elution HPLC. Fragment ions observed in the ESI mass spectra facilitated identification of peptides obtained by HPDC tryptic mapping. PMID- 1744203 TI - Application of capillary zone electrophoresis to the characterization of multiple antigen peptides. AB - Capillary zone electrophoresis (CZE) was applied to the analysis of a recently described class of synthetic branched peptides, multiple antigen peptides (MAPs). In comparison with high-performance liquid chromatography (HPLC), CZE showed superior resolution of minor impurities in samples of MAPs obtained by preparative chromatography. MAPs that differed only in the substitution of uncharged residues (Ala-Ser) could be separated by the addition of organic solvents (acetonitrile, methanol, ethanol) to the aqueous background electrolyte. PMID- 1744204 TI - Performances and limits of plasma desorption mass spectrometry in the primary structure determination of proteins. AB - The resolution, sensitivity, matrix effect, cationization and spectral suppression in plasma desorption mass spectrometry (PD-MS) were investigated in the context of peptide analysis. Excessive cationization may be avoided by the addition of citric acid on the target. The importance of the relative net charge of peptides in PD-MS spectra suppression was confirmed. Esterification of peptides is shown to be an easy way to overcome spectral suppression. Provided that cationization and spectral suppression of peptides are under control, PD-MS is an excellent tool for protein sequence analysis, affording the necessary complement to automated Edman degradation. PMID- 1744205 TI - Adsorption-desorption isotherm hysteresis of beta-lactoglobulin A with a weakly hydrophobic surface. AB - Adsorption-desorption isotherms of bovine beta-lactoglobulin A (beta-lact A) on a weakly hydrophobic stationary phase (C1-ether) were measured by frontal analysis. The adsorption isotherms obtained at different pH were found to be dramatically different in shape, column capacity and desorption reversibility. At pH 4.5, an S shaped adsorption isotherm was observed whereas at pH 6.0 a Langmuir isotherm was found. In addition, the desorption isotherm at pH 6.0 was found to overlap with the adsorption isotherm, and the adsorption-desorption process of beta-lact A under this condition could be characterized by a fully reversible Langmuir model. The desorption isotherm at pH 4.5, however, did not retrace the adsorption isotherm, resulting in hysteresis loops. A higher aggregate (tetramer) of beta lact A is shown to be in an equilibrium with the beta-lact A protomer (dimer) at pH 4.5 whereas the dimer alone is predominant at pH 6.0. It is further shown that changes in the absorption coefficient between the adsorption and the desorption cycles for the tetramer at pH 4.5 can account for the hysteresis. The results demonstrate that pH can be a sensitive parameter in protein adsorption isotherm behavior and ultimately the behavior of species in preparative-scale chromatography. PMID- 1744206 TI - Laser-excited fluorescence detection of gas-phase chromatography eluates. AB - A high-spectral-resolution laser-excited molecular fluorescence gas chromatographic (GC) detection system is evaluated. It utilizes a pulsed supersonic jet expansion to yield very-narrow-bandwidth (e.g. less than or equal to 0.1 nm) fluorescence excitation spectra that may be rapidly scanned via a tunable dye laser. A microcomputer synchronizes the entire system, collects data, performs calculations, and creates visual displays of results. The laser-excited fluorescence detection system was interfaced to a gas chromatograph to exploit both the selectivity of the chromatography and the excellent spectral selectivity of the detector. Fluorescence excitation chromatograms were acquired by monitoring fluorescence emission from selected transition wavelengths characteristic of the GC eluates. The excitation wavelengths were also programmed to change at appropriate retention times to provide greatest selectivities for individual analytes as they eluted, and to allow multiple analytes to be determined in a single elution. Response factors for the system varied appreciably from run to run, which precluded the use of external standard quantitation procedures. However, excellent stabilities for within-run relative response factors were sufficient to allow for good quantitative measurements using internal standard techniques. PMID- 1744207 TI - Influence of mobile phase composition on evaluation of lipophilicity by partition chromatography. AB - The problems of the concentration dependence of retention indices and the applicability of extrapolated values in the evaluation of lipophilicity were studied. The reversed-phase high-performance liquid chromatography of arylalkanoic acids were carried out with experimental data for substituted estra 1,3,5 (10)-trienes, benzodiazepines, dermorphine derivatives and dansylamides selected from the literature for this purpose. Fair linear relationships between slopes of concentration dependences and extrapolated and non-extrapolated values of RM and log k' were found. Equivalence of these indices in the evaluation of lipophilicity can be inferred. Statistically significant dependences of log P (sigma pi) values on concentration slopes make it possible to use them as new parameters of lipophilicity. The goodness of fit of these relationships increases when the values of ET(30), as a measure of the solvatochromic solvent polarity of mobile phases, are used instead of the change in modifier concentration. PMID- 1744208 TI - Characterization and determination of organic compounds in the mutagenic XAD-2 extracts of drinking water. AB - Amberlite XAD-2 extracts, which exhibit mutagenicity in the Ames assays, of drinking water sampled each month during the period from April 1988 to March 1989 were studied in order to characterize and determine the organic pollutants. The major organic pollutants were phthalate ester plasticizers such as dibutyl and di(2-ethylhexyl) phthalate. Several polynuclear aromatic hydrocarbons (PAHs) and the organocholorine pesticide oxadiazon were also identified to be present at low concentrations. The XAD-extractable and chromatographable organic pollutants were found to be composed of PAHs with a mean concentration of 0.136 micrograms/l(ca. 10% of the total amount of organic compounds detected), phthalates with a mean value of 0.405 micrograms/l(ca. 30%) and other compounds with a mean value of 0.845 micrograms/l(ca. 60%). The concentrations and compositions of these organic pollutants were correlated with the effective rainfall content of the river and with the water temperature. PMID- 1744209 TI - Liquid chromatographic method for the determination of the carbohydrate moiety of glycoproteins. Application to alpha 1-acid glycoprotein and tissue plasminogen activator. AB - A rapid procedure is described for the qualitative and quantitative analysis of the carbohydrate composition of glycoproteins by liquid chromatography with light scattering detection. The analysis was carried out in three steps. First, the glycoprotein samples were purified by a two-step purification on a Sephadex G-25 column with a 90% yield. Second, the selectivity of the separation and the sensitivity of detection of monosaccharides, as methyl glycosides obtained by direct methanolysis of glycoproteins, were improved by modified simplex optimization of the methanolysis parameters (temperature, methanolic hydrochloric acid strength and reaction time) determined at 66 degrees C, 1.2 M and 8.1 h for alpha 1-acid glycoprotein (alpha-AGP) and 73 degrees C, 1.5 M and 12.5 h for tissue plasminogen activator (tPA). Finally, the method was applied to the determination of the carbohydrate moiety of the two N-glycosylated glycoproteins alpha-AGP and tPA. PMID- 1744210 TI - Column liquid chromatographic determination of carbadox and olaquindox in feeds. AB - A column liquid chromatographic method for simultaneous determination of carbadox and olaquindox in swine feeds is described. The drugs were extracted from feeds with carbon tetrachloride-dimethylformamide (80:20) at 60 degrees C for 30 min. The extract was mixed with water (25:45). After centrifugation the aqueous layer was chromatographed on a reversed-phase column using gradient elution and ultraviolet detection at wavelengths of 305 and 262 nm. Recoveries from samples fortified at levels of 20-50 ppm were 92 +/- 9% for carbadox and 93 +/- 6% for olaquindox (means +/- standard deviations, n = 71). PMID- 1744211 TI - Liquid chromatographic method for the determination of calcium cyanamide using pre-column derivatization. AB - A specific and stability-indicating high-performance liquid chromatographic (HPLC) method has been developed for the analysis of calcium cyanamide in bulk material and dosage form. Calcium cyanamide in samples was converted into dansyl cyanamide. A muBondapak C18 column was employed for HPLC with 0.01 M sodium phosphate (pH 6.3)-acetonitrile (75:25, v/v) as the mobile phase. The proposed HPLC method was validated for linearity, specificity, accuracy and reproducibility. PMID- 1744212 TI - Determination of sulfonamides by liquid chromatography, ultraviolet diode array detection and ion-spray tandem mass spectrometry with application to cultured salmon flesh. AB - Ion-spray mass spectrometry was investigated for the analysis of 21 antibacterial sulfonamide drugs. All of the sulfonamides analyzed gave positive ion mass spectra with abundant protonated molecules and no fragmentation. Tandem mass spectrometry (MS-MS) using collision-induced dissociation provided structural information, allowing the identification of common fragmentation pathways and the differentiation of isomeric and isobaric sulfonamides. A reversed-phase high performance liquid chromatographic method was developed, using gradient elution and ultraviolet diode-array detection (DAD), enabling the separation of 16 of the sulfonamides. Combined liquid chromatography (LC)-MS was accomplished using the ion-spray interface. Analyses of a mixture of sulfonamide standards were performed with gradient elution and the mass spectrometer configured for full scan acquisition, selected-ion monitoring, or selected-reaction monitoring. Procedures for the analysis of sulfadimethoxine (SDM), a representative sulfonamide used in the aquaculture industry, are described. The presence of SDM in cultured salmon flesh was confirmed at levels as low as 25 ng/g by a combination of LC-DAD and LC-MS-MS. PMID- 1744213 TI - Pre-column derivatization of sulfa drugs with fluorescamine and high-performance liquid chromatographic determination at their residual levels in meat and meat products. AB - A rapid, sensitive and selective high-performance liquid chromatographic method is described for simultaneous determination of eight sulfa drugs in meat and meat products using pre-column derivatization with fluorescamine. The drugs are sulfisomidine, sulfadiazine, sulfamerazine, sulfadimidine, sulfamonomethoxine, sulfamethoxazole, sulfadimethoxine and sulfaquinoxaline. The method includes blender extraction of 3-g samples with chloroform, partition with 3 M hydrochloric acid, derivatization with fluorescamine at pH 3.0 and subsequent high-performance liquid chromatographic analysis on a C18 column with fluorescence detection at an excitation wavelength of 405 nm and an emission wavelength of 495 nm. The drugs were separated with a mobile phase of acetonitrile-2% acetic acid (3:5) at 55 degrees C. The average recovery from samples fortified at 0.1 ng/g was 92.6% with a coefficient of variation of 6.2%. The detection limit was 0.01 ng/g for sulfaquinoxaline and 0.005 ng/g for the other seven drugs. The method was field-tested in a survey of 37 samples including beef (five), pork (seven), chicken (seven), ham (five), sausage (eight), bacon (two) and roast beef (three). Sulfadimidine was detected in one pork sample at the level of 0.295 ng/g and in ham at 0.178 ng/g. PMID- 1744214 TI - Determination of hexahydrophthalic anhydride in air using gas chromatography. AB - Two methods for the determination of hexahydrophthalic anhydride (HHPA) in air were developed. In a solid sorbent method, HHPA was sampled in Amberlite XAD-2 tubes, eluted in toluene and analysed by gas chromatography with flame ionization detection. The sampling rates were 0.2 and 1.0 l/min. At 15 micrograms/m3 (relative humidity less than 2%) and 27 micrograms/m3 (relative humidity 70%) no breakthrough was observed. However, at 160 micrograms/m3 (relative humidity less than 2%), 6% breakthrough was found. The sampling efficiency of the sampling rates 0.2 and 1.0 l/min did not differ. In a bubbler method, HHPA was sampled in bubblers filled with 0.1 M sodium hydroxide solution. The sodium salt of hexahydrophthalic acid was formed. No breakthrough was observed using a sampling rate of 1.0 l/min. The samples were stable during storage for eight weeks in a refrigerator. The HHP acid was esterified with methanol-boron trifluoride and analysed by gas chromatography-flame ionization detection. Apparatus for the generation of standard atmospheres of HHPA, in the range of 10-3000 micrograms/m3, was developed using the diffusion principle. For the solid sorbent method the precision (coefficient of variation) of the overall method was 2-7%, and for the bubbler method 3-19% (range 15-160 micrograms HHPA/m3; relative humidity = less than 2-70%). A comparison between the two methods was performed using the standard atmosphere. The concentrations found by the solid sorbent method were 86-98% of those found by the bubbler method (range 15-160 micrograms HHPA per m3; relative humidity = less than 2-70%). In work environment air, 93% was found using the solid sorbent method relative to the bubbler method at a mean concentration of 330 micrograms/m3 (coefficient of variation = 39%; range 200-540 micrograms/m3). For both methods, concentrations greater than 3 micrograms/m3 could be quantified at 60 min sampling with a sampling rate of 1.0 l/min. PMID- 1744215 TI - Stereoisomeric purity determination of captopril by capillary gas chromatography. AB - The GC method developed for the stereoisomeric purity determination of captopril is based on the combined information derived from the analyses of the captopril sample on two GC systems, one with a chiral and the other with an achiral column. The limit of detection has been determined to be 0.02% (w/w) for (R,S) or (S,R) and 0.03% for (R,R), with corresponding minimum quantifiable levels of 0.08% and 0.09%. PMID- 1744216 TI - Comparison of the performance of immunosorbents prepared by site-directed or random coupling of monoclonal antibodies. AB - The majority of methods used to prepare immunosorbents immobilize antibodies through their reactive amino acid residues. The bound antibody activity of these immunosorbents is low. Hydrazide-based matrices couple antibodies through carbohydrate chains frequently located in the Fc region. This paper reports a comparative study of the performance of immunosorbents prepared by cyanogen bromide or hydrazide immobilization methods. The experiments utilized murine monoclonal antibodies to the human plasma proteins Factor IX or Protein C. The antibodies were immobilized at low densities to beaded agarose matrices which had similar properties. The hydrazide immunosorbents had binding efficiencies which were lower (anti-Factor IX) or up to 1.6-fold higher (anti-Protein C) than comparable cyanogen bromide coupled gels. However, there was no improvement in performance due to lower recoveries of bound protein from the hydrazide gels. Control experiments demonstrated that oxidation of antibody which is required for its coupling to hydrazide gels had no effect on antibody binding to antigen. Our results indicate that, as with cyanogen bromide coupling methods, site-directed immobilization through carbohydrate residues results in a restricted ability to bind to antigen. Both monoclonals were found to contain carbohydrate in their Fab' regions through which coupling may have occurred. The frequency of carbohydrate in the Fab region and the ability to control glycosylation at these sites are factors which may impact the utility of carbohydrate-directed immobilization of antibodies. PMID- 1744217 TI - Use of M13 single-stranded DNA digoxigenin labelled probe for detection of human parvovirus B19 viraemia. AB - A dot-blot hybridization assay for serum B19 DNA is described using a non radioactive (digoxigenin) M13 single-stranded DNA probe. The assay is sensitive (0.3 pg of B19 DNA) and has several advantages over similar assays which use radioactive or non-radioactive labelled plasmid probe for the routine detection of B19 DNA in sera. PMID- 1744218 TI - Production of monoclonal antibodies reactive with a denatured form of the Friend murine leukemia virus gp70 envelope protein: use in a focal infectivity assay, immunohistochemical studies, electron microscopy and western blotting. AB - Four monoclonal antibodies were selected for their ability to recognize the envelope protein of Friend murine leukemia virus (F-MuLV) in methanol-fixed tissue culture cells. Each of these monoclonal antibodies was found to react only with F-MuLV. By using recombinant retroviruses, it was determined that each of the monoclonal antibodies recognized the C-terminal one-third of the F-MuLV gp70 envelope protein. The monoclonal antibodies were effective in radioimmunoprecipitation of F-MuLV proteins, and one of the antibodies, 720, was also effective in Western blotting. The ability of antibody 720 to react with F MuLV in methanol-fixed cells facilitated the use of a sensitive immunoperoxidase method with a focal virus infectivity assay. In immunohistochemical studies using light microscopy, antibody 720 could specifically label F-MuLV-infected cells in acetone-fixed tissue sections from F-MuLV-infected animals. Finally, in immuno gold labelling studies using electron microscopy, antibody 720 could be used to distinguish F-MuLV from amphotropic MuLV. PMID- 1744219 TI - The diagnosis of acute viral hepatitis A or B by microparticle enzyme immunoassay. AB - The traditional approach to the diagnosis of viral hepatitis has been to collect a serum sample and to test it for the presence of hepatitis B surface antigen (HBsAg), IgM to the core of HBV (anti-HBc IgM) and IgM to HAV (anti-HAV IgM) by solid phase radio- or enzyme immunoassays. Microparticle enzyme immunoassay technology (IMx-Abbott Laboratories) has been introduced as an automated carousel system for the detection of these markers. A side-by-side, blinded comparison of IMx to current IA was performed for HBsAg on 659 specimens submitted from March to July 1990, of which 72 (10.8%) were positive by AUSRIA (Abbott RIA for HBsAg) and 2 of these were discordant in IMx. Both were near the cutoff and by confirmatory testing one was positive and the other negative. Forty three percent (25/58) of frozen stored sera tested for anti-HBc IgM, by IMx, were positive by EIA (Corzyme M). One specimen near the cutoff was negative by EIA but weakly positive by IMx. Anti-HAV IgM was found in 21.8% (46/211) of sera with 100% correlation by IMx. Thus IMx had the following percent sensitivies and specificities: HBsAg; 98.6, 99.9; anti-HBc IgM; 100, 99.9; anti-HAV IgM; 100, 100. The test set-up times for the 3 markers in the IMx were similar to the RIA and EIA. The turnover time was 45 min for a full IMx carousel compared to: AUSRIA short incubation (4 h), or long incubation (14 h); Corzyme M-short (4.75 h) or long (20 h); anti-HAV IgM (23 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744220 TI - Development of a dot-immunobinding assay for detection of citrus tristeza virus. AB - The dot-immunobinding assay (DIBA) was adapted for detection of citrus tristeza virus (CTV) and compared with DAS-ELISA and DAS-indirect ELISA. DIBA was easy to perform and as sensitive as either ELISA procedure for CTV diagnosis. The entire test could be performed in 2-3 h using polyclonal antibodies, with minimal laboratory equipment. Three different polyclonal antibodies gave a strong positive reaction with 12 selected CTV isolates; however, each serum had to be cross-absorbed with sap from healthy plants before use. The broad spectrum 3DF1 monoclonal antibody reacted with most of the CTV isolates. The MCA-13 strain specific monoclonal antibody was specific for most severe CTV isolates. As blocking agents, 3% bovine serum albumin (BSA), 3% gelatin, 0.5% non-fat dry milk or 5% Triton X-100 gave an adequate white background on the nitrocellulose membranes and permitted discrimination between infected and healthy samples. However, 3% gelatin gave the best contrast between green for the healthy samples, and purple color for infected samples. PMID- 1744221 TI - Serological techniques for detection of citrus tristeza virus. AB - Citrus tristeza virus (CTV) is the most economically important virus disease of citrus. In the last ten years, remarkable progress has been achieved in the development and improvement of new serological methods for CTV detection so that serology has become a dependable tool for many research, extension and regulatory purposes worldwide. CTV-specific polyclonal antisera and monoclonal antibodies have been developed in different research laboratories and used extensively in a wide range of different studies. This review describes the diverse serological methods developed for CTV detection and analyzes the advantages, disadvantages, relative sensitivity, applications, and present status of each method. PMID- 1744222 TI - [Advances in hepatitis virus research. The clinical issues of hepatitis C]. PMID- 1744223 TI - [Radionuclide ventriculographic evaluation of exercised left ventricular performance in asymptomatic diabetic patients]. AB - Radionuclide ventriculography was made in 49 asymptomatic diabetic patients, aged 30-70 years, to investigate cardiac function. Comparisons were made with 33 age- and sex-matched non-diabetic controls. Radionuclide ventriculography was performed at rest and during dynamic exercise by multigraded, supine bicycle ergometer. The resting left ventricular ejection fractions were similar between the diabetic patients and control subjects. No significant rise in the left ventricular ejection fractions during dynamic exercise was observed in the diabetic patients [58.4 +/- 9.8% (mean +/- SD) to 60.3 +/- 9.9]. In the control subjects, the left ventricular ejection fractions increased during dynamic exercise [59.3 +/- 8.4 to 63.0 +/- 11.4 (p less than 0.05)]. Peak ejection rates were similar in both groups at rest [-2.62 +/- 0.64 (s-1) vs -2.66 +/- 0.52] and during dynamic exercise [-3.25 +/- 0.74 vs -3.23 +/- 0.90]. Time to end-systole were similar in both groups at rest [315 +/- 42 (ms) vs 309 +/- 42] and during dynamic exercise [258 +/- 37 vs 262 +/- 37]. The resting peak filling rates were similar in both groups [2.27 +/- 0.62 (s-1) vs 2.45 +/- 0.58], and the peak filling rates increased (p less than 0.001) during dynamic exercise in both groups [2.68 +/- 0.61 vs 3.28 +/- 0.74]. However, the percent changes of the peak filling rates were significantly lower in diabetic patients (p less than 0.001). In four of the diabetic patients, hypokinesis of the intraventricular septum was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744224 TI - [Abnormal left ventricular function in diabetic patients, with special reference to abnormal diastolic function. Preclinical findings through diabetic cardiomyopathy]. AB - In order to elucidate the nature of cardiovascular involvement in diabetes mellitus (DM), we analyzed a high-resolution time-activity cure obtained from a gated equilibrium radionuclide left ventriculography (RLVG) in 50 cases consisting of 3 groups; G-C: normal controls (n = 17, male 10 and female 7, age 49.6 +/- 9.6 years old), G-DM: patients with DM without clinical signs of ischemic heart disease (n = 17, male 13 and female 4, age 58.3 +/- 9.9 years old), and G-DM + MI: patients with DM complicated myocardial infarction (n = 16, male 14 and female 2, age 59.5 +/- 10.0 years old). Indexes of cardiac performance during both systole and diastole obtained from RLVG were as follows: ejection fraction (EF), peak ejection rate (PER), peak filling rate (PFR), time from the start of systole to PER (T-PER1), time from end-systole to PFR (T-PFR2), diastolic relaxation rate (DRR) during the first third of diastole (DRRe) and during the whole diastole (DRRt). There were no significant differences in EF and PER (systolic parameters) between G-C and G-DM. These parameters were significantly lower only in G-DM +/- MI. However, DRRe and DRRt (diastolic parameters) were significantly smaller, and T-PFR1 and T-PFR2 were longer in G-DM and G-DM + MI than in G-C. PFR was significantly lower in G-DM + MI than in the other two groups and there was no significant difference between G-DM and G-C. In addition, DRRe was significantly lower in patients with retinopathy than in patients without retinopathy in both G-DM and G-DM + MI. It is concluded that DM can cause impairment of diastolic relaxation of the left ventricle before the appearance of distinct cardiac dysfunction during systole and that it might be probably due to microangiopathy. These results suggest a poor prognosis of MI in patients with DM. PMID- 1744225 TI - [The pulmonary function and histopathological studies of the lung in diabetes mellitus]. AB - The pulmonary function and microscopic change of the lungs of diabetic patients were examined and compared with those of non-diabetic patients to assess the diabetic microangiopathy in lung. For pulmonary function study, spirogram flow volume curve, diffusing capacity and arterial blood gas analysis were performed in 52 diabetic patients and 48 age- and sex-matched control subjects. Diffusing capacity, % vital capacity, total lung capacity, residual volume and 25% maximal expiratory flow were significantly less in the diabetic group than in the control group. PaO2 was also decreased in the diabetic group. There were no significant differences between the two groups in the other parameters. For histopathological study, the lungs of 35 autopsied cases of a diabetic group and 26 autopsied cases of a non-diabetic group. There were no significant differences in age and sex between the two groups. The two groups were compared and studied by measuring the thickness of alveolar capillary walls, pulmonary arteriolar walls and alveolar walls with a light microscope and an eye piece micrometer. The alveolar capillary walls, the pulmonary arteriolar walls and the alveolar walls had thickened significantly in the diabetic patients. These studies suggested that histological changes (microangiopathy) in the lungs are a cause of pulmonary function abnormalities. PMID- 1744226 TI - [Enhancement of epidermal growth factor receptor (EGF-R) expression on glioma cells by cytokines]. AB - Recombinant tumor necrosis factor alpha (TNF-alpha) significantly enhanced epidermal growth factor receptor (EGF-R) expression in U373-MG glioma cell line as determined by binding of anti-EGF-R monoclonal antibody (MAb) 425. The optimal dose of TNF-alpha was 1000 U/ml of media. When TNF-alpha was combined with recombinant interferon gamma (IFN-gamma), further upregulation of EGF-R was observed. However, IFN-gamma itself did not show any EGF-R enhancement in this cell line. Scatchard analysis of receptor binding revealed that this enhancement of EGF-R expression was due to an increase in the EGF-R density. TNF-alpha did not affect expression of other brain tumor-associated antigens defined by MAb ASHE2, ASHG4 and ASAY1. Cultured fibroblasts showed no upregulation of EGF-R by TNF-alpha, suggesting a differential effect of TNF-alpha on EGF-R expression on glioma cells and normal cells. We investigated whether TNF-alpha treatment of glioma cells increased the tumoricidal effects of radiolabeled MAb 425 which correlate with MAb density on tumor cell surfaces. Growth inhibition of glioma cells in culture by 125I-labeled MAb 425 was significantly enhanced after treatment of the cells with TNF-alpha. In previous clinical trials, 125I-labeled MAb 425 has shown immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled MAb 425 and cytokines. PMID- 1744227 TI - [Evaluation of acute myocardial infarction by 201T1 single-photon emission computed tomography using scoring system]. AB - In 36 patients with acute myocardial infarction (AMI) 201T1 single-photon emission computed tomography (SPECT) examinations were performed in a relatively early phase of AMI. The short and long axis views of the left ventricle (LV) were divided into 6 segments. Images of each segment were assigned scores (segmental scores) based on a visual evaluation of the extent of 210T1 accumulations as follows: 1 = normal; 2 = relatively low; 3 = low; 4 = severely low; 5 = cold. The sum total of the segmental scores constituted the SPECT score. SPECT scores were compared with maxGOT, maxLDH, maxCPK and maxCK-MB, Killip classification and Forrester hemodynamic subset on admission, and LV ejection fraction (LVEF). Segmental scores were compared with LV wall motion evaluated by left ventriculography. The results are summarized as follows: 1) There were significant correlations between SPECT scores and maxGOT, maxLDH, maxCPK and maxCK-MB (r = 0.62, r = 0.60, r = 0.51 and r = 0.39, respectively). 2) SPECT scores in patients with Killip group III were significantly higher than in patients with Killip group I + II (p less than 0.05). However, no significant differences in maxGOT, maxLDH, maxCPK and maxCK-MB were observed between patients with Killip group III and those with Killip group I + II. 3) SPECT scores were significantly higher in patients with Forrester group III + IV than in patients with Forrester group I + II (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744228 TI - [An experimental study to determine the most effective delay procedures on secondary vascularized skin island flaps]. AB - Secondary vascularized flaps made from implanted vascular bundles in the subcutaneous tissues have dominant vascularities. Animal experiments were performed using white rabbits, two types of skin flaps were made on their backs. The first delay procedure was performed on the left side where the vascular bundle had been implanted with an elevation of distally based flap (size 2 cm x 7 cm). 28 out of 32, secondary vascularized skin island flaps survived either partially or completely in the first procedure. Moreover, the first delay method was observed to be efficacious in 15 out of 16 cases (p less than 0.01). The viability of vascular bundles of secondary vascularized flap was thus proved. The first stage of the second delay procedure was performed in bilateral side using the same procedure as the first delay. Two weeks later, two types of delay method were carried out. On the left side, a proximally based flap (size 2 cm x 7 cm) was made at the distal area of the first delay flap. On the right side, a bipedicled flap was made (size 2 cm x 14 cm). These flaps were elevated as secondary vascularized skin island flaps two weeks later. In all cases, the latter procedure produced a longer survival rate compared with the former (p less than 0.01). It was concluded experimentally that the most effective second delay procedure was the bipedicled flap method. PMID- 1744229 TI - [Study of fetal responses to external vibratory acoustic stimulation]. AB - Effects of a 5-second external vibratory acoustic stimulation (VAS, 500 Hz, 75 db) were studied in 155 healthy pregnant women from 34 to 41 weeks' gestational age on the fetal heart rate and gross fetal body movement. Fetal behavioral states were also studied in 88 out of the 155 patients. The following results and conclusions were obtained. 1) VAS induced significant increases in the fetal heart rate baseline, the mean amplitude, the mean duration, and the mean time spent % of fetal heart rate accelerations and gross fetal body movements. 2) VSA induced significant changes in fetal behavioral states at states 1F and 3F, but no changes in states 2F and 4F. 3) Reaction to VAS was recognized also in the low birth weight (less than 2,500 g) group, but the duration of the reaction was shorter than that in the normal (greater than or equal to 2,500 g) group. 4) By lowering the incidence of false non reactive NST with VAS test, it was possible to predict the fetal prognosis better than NST alone. 5) Inasmuch as VAS changed the fetal behavioral state from resting phase to active phase, the use of VAS in addition to NST was very helpful in more accurate understanding of fetal heart rate monitoring. PMID- 1744230 TI - [Innervation of the sacroiliac joint. Macroscopical and histological studies]. AB - Macroscopical and histological studies were carried out to clarify nerve innervation of the sacroiliac joint which is believed to have a role in the development of low back pain. Eighteen Japanese adult cadavers were used for gross anatomical examination and six for histological examination of the nerve supply to the joint. The results were as follows: 1) It is suggested by the gross examination that the upper ventral portion of the joint is mainly innervated by the ventral ramus of the 5th lumber nerve. 2) The lower ventral portion of the joint was mainly supplied by the ramus of the 2nd sacral nerve or branches from the sacral plexus. 3) Lateral branches of the dorsal ramus of the 5th lumber nerve were considered to be the main nerves which innervated the upper dorsal portion of the joint. 4) The lower dorsal portion was innervated by nerves arising from a plexus composed of lateral branches of the dorsal rami of the sacral nerves. 5) The nerves which innervate the joint range in diameter from 0.292 mm to 0.997 mm, and no difference was found among those in the four subdivisions of the joint. 6) Histological examination revealed that nerve fibers and the terminals were present in the joint capsule and adjoining ligaments. The nerve fibers varied from 0.2 micron to 2.5 microns in diameter and ended with five morphologically different terminals. PMID- 1744231 TI - [Percutaneous transluminal coronary angioplasty. The primary results from the registry of the First Department of Internal Medicine, Nippon Medical School]. PMID- 1744232 TI - [Reperfusion therapy for acute coronary occlusion]. PMID- 1744233 TI - Preventing war. PMID- 1744234 TI - Health in development. PMID- 1744235 TI - Public health, not social warfare: a public health approach to illegal drug policy. AB - This article makes three major arguments: (I) the current War on Drugs undercuts public health values and premises, resulting in a war on the poor, disenfranchised, people of color, the homeless, and the unemployed; (2) drug problems should be addressed primarily within the realm of public health policy rather than criminal justice policy; and (3) to achieve a viable public health drug policy, the public health community needs to build grassroots support and become effective activists. The article reviews the history of past drug wars, analyzes recent trends in illegal drug use and problems, and critiques current policy initiatives and their consequences. It then outlines a comprehensive, public health approach to addressing illegal drug problems, and concludes with an analysis of what steps are needed to become effective in the public policy arena. PMID- 1744236 TI - Generational equity and public health policy: a critique of "age/race war" thinking. AB - A potent new tool in the politics of fiscal retrenchment lies in the creation of a framework for policy analysis which implicitly or explicitly "blames" the old for poverty and economic hardships in the young. This paper examines the recent efforts to promulgate this generational equity or "age/race wars" perspective and demonstrates that opinion poll data fail to support the rhetoric of growing age/race group antagonisms over entitlement programs for the old. The assumptions underlying the generational equity framework are critiqued, and the race and ethnic issues embedded within this framework are examined. In particular, we explore spurious assumptions concerning the relative financial wellbeing of the elderly, escalating Social Security and Medicare costs as a primary cause of poverty in the young, and growing resentment of programs for the old among minorities and youth. Attempts to deligitimate the claims of the elderly through the advancement of the ideology of age/race wars are seen to have significant implications for public health policy, with the country's recent experience with the Medicare Catastrophic Coverage Act serving as an important case in point. The need for an alternative policy framework stressing the interdependence of generations is suggested, and some guiding principles put forward toward the development of such an alternative framework. PMID- 1744237 TI - Population behavior change: a theory-based approach. AB - Behavioral science provides useful ideas about how programs of mass communication and community participation can produce synergistic influences on the lifestyles and policy decisions of populations and their representatives. Media campaigns featuring real-life behavior models and community networks mobilized to promote behavior change provide a theoretically sound paradigm for community-level activities to accelerate the diffusion of innovation in health. Illustrative case studies demonstrate how behavioral science concepts can be applied to preventing HIV infections and to promoting citizen lobbying against selected nuclear weapons systems. PMID- 1744238 TI - The reform of the British National Health Service. AB - After a 40-year existence as a service sheltered from market influences, the reforms introduced in 1990 and coming into effect at this time profoundly alter the role of hospitals and primary care physicians. The hospitals may sell and purchase services across former boundaries; the family doctor has a host of additional duties under the new contract. The details of these arrangements and professional criticisms are described. PMID- 1744239 TI - Resolution: From the Gulf War to peace and disarmament. World Council of Health Worker Organizations for Social Well-Being, Health and Peace. PMID- 1744240 TI - Serotoninergic innervation of the thalamus in the primate: an immunohistochemical study. AB - Little is known of the serotoninergic innervation of the thalamus in primates; therefore, we undertook a detailed study of the distribution of 5 hydroxytryptamine (5-HT)-immunoreactive neuronal profiles in the thalamus of the squirrel monkey (Saimiri sciureus) with a specific antibody directly raised against 5-HT. All thalamic nuclei in the squirrel monkey displayed 5-HT immunoreactive fibers, but none contained immunopositive cell bodies. The 5-HT innervation of the thalamus derived from extrinsic fibers arising mostly from the midbrain raphe nuclei and forming the transtegmental system. Most of the fibers destined to the thalamus collected into a major bundle that swept dorsoventrally within the midbrain tegmentum and coursed beneath the thalamus along its entire caudorostral extent. Several fiber fascicles broke off from this main bundle at different levels and ascended dorsally to innervate the various thalamic nuclei. Overall, the 5-HT innervation of the thalamus in the squirrel monkey was more massive than would have been expected from earlier studies in nonprimate species. Marked differences in the regional density of innervation were noted both between the various nuclei and within single nuclei. The most densely innervated nuclei were those delineating the principal subdivisions of the thalamic mass, that is, the midline, rostral intralaminar, limitans, and reticular nuclei, where very dense fields of isolated axonal varicosities occurred. In contrast to the rostral intralaminar nuclei, which were rather uniformly innervated, the centre median/parafascicular complex contained immunoreactive fibers and isolated varicosities distributed according to a mediolateral gradient. The habenula and the ventral anterior nucleus were among the most weakly innervated nuclei. In the latter nucleus, as well as in more densely innervated nuclei, thin varicose fibers formed numerous pericellular contacts on cell bodies and proximal dendrites of thalamic neurons. The 5-HT innervation of the lateral nuclear group as well as that of the medial and lateral geniculate nuclei ranged from very weak to dense. The mediodorsal nucleus displayed a highly heterogeneous 5-HT innervation that varied from weak in its central portion to moderate or dense in its medial and lateral borders. A moderate 5-HT innervation was observed in the anterior nuclear group. The surprisingly dense and heterogeneous 5-HT innervation of the thalamus noted in the present study suggests that serotonin may be involved in several specific functions of the thalamus in primates. PMID- 1744241 TI - Ultrastructural changes in the nucleolus of facial motor neurons following axotomy during an early critical period in development. AB - In this study, the effects of axotomy on the ultrastructure of the nucleolus and associated organelles were examined in fetal, newborn, and early postnatal facial motoneurons of the hamster. Golden hamsters used for this study were the 14-day fetus, newborn (0 days; less than 6 hr) and 2, 4, 7, and 9 days postnatal ages, with 3 animals per group. For prenatal surgeries, pregnant hamsters were anesthetized and the facial nerves severed in the fetuses via electrocautery through the uterine wall and amniotic membrane. For postnatal surgeries, the animals were anesthetized and the right facial nerve exposed and severed at its exit from the stylomastoid foramen. At the appropriate postoperative times, the animals were reanesthetized and perfused-fixed. The facial nuclear groups were dissected and processed for routine electron microscopy. Microbody and coiled body frequencies were determined from the number of neurons containing these structures per number of neurons sampled per animal in each experimental or control group and subjected to statistical analysis. Nucleolar reactive changes that occurred during this developmental sequence fell into two major categories. The first category displayed by most injured cells consisted of an initial compacting of fibrillar material and reduction in vacuolar space. The second category appeared to represent a progression from this first stage of nucleolar reactivity into degenerative changes involving a striking segregation of nucleolar components into five distinct regions. The incidence of microbodies increased as a result of axotomy, whereas the presence of coiled bodies decreased at the later postoperative stages in the older animals. With increasing age and nucleolar maturation, the nucleolar reactive pattern became less pronounced and severe, and neuronal survival predominated. It appears, therefore, that the two categories of nucleolar changes following axotomy during early development correlate with changes observed in nucleoli under conditions of rRNA downregulation. It is hypothesized from these results that a key step in the ability of neurons to survive axotomy and successfully regenerate at these early developmental stages occurs at some point in ribosomal RNA transcription and/or processing. Complementary information at the molecular level concerning changes in nucleolar synthetic activity and ribosome production will be necessary to test this hypothesis. PMID- 1744242 TI - The mossy cells of the fascia dentata: a comparative study of their fine structure and synaptic connections in rodents and primates. AB - In this study the fine structure and synaptic connections of mossy cells in the rat and monkey fascia dentata were analyzed. In order to study commissural connections of identified mossy cells in the rat, hilar neurons were retrogradely labeled by horseradish peroxidase (HRP) or Fast Blue (FB) injections into the contralateral hippocampus. Vibratome sections containing retrogradely HRP-labeled hilar neurons were Golgi-impregnated and gold-toned. Hilar commissural neurons identified by contralateral FB injection were intracellularly labeled with Lucifer Yellow (LY). Lucifer Yellow staining was made electron-dense by photoconversion thereby allowing for an electron microscopic analysis of the retrogradely labeled and intracellularly stained neurons. With these two different approaches, we succeeded in identifying rat mossy cells projecting to the contralateral hippocampus. Mossy cells in the fascia dentata of primates (Papio anubis, Macaca mulatta, Saimiri sciureus) were, like mossy cells of rats, either Golgi-impregnated and gold-toned or intracellularly injected with LY. No major differences were found between mossy cells of rats and monkeys. The mossy cell dendrites originated from the two sides of an ovoid cell body and were mainly oriented parallel to the granule cell layer. In contrast to the rat, dendrites of mossy cells in the primate did not respect the granule cell layer and penetrated frequently into the molecular layer. The occurrence of excrescences on proximal dendrites was a characteristic feature of all mossy cells. These large spines were more complex in the primate than in the rat. In both rats and primates they formed numerous asymmetric synapses with large boutons of mossy fibers. Peripheral dendrites were covered with small, simple spines. Interestingly, these peripheral dendrites lacking excrescences also established asymmetric synapses with mossy fiber boutons as well as asymmetric and symmetric contacts with smaller terminals of unknown origin. These findings indicate that in both rats and primates the thorny excrescences are not the only target of the mossy terminals. While the proximal portions of the mossy cell dendrites appear to be exclusively contacted by the granule cells, a larger number of neuron types may converge on the distal dendrites. The axons of mossy cells, in both rats and primates, although incompletely stained with the present methods, were seen to ramify in the hilar region. Our results demonstrate that, despite minor species differences, the mossy cells of the fascia dentata represent a cell type that is preserved in phylogenetically distant species. PMID- 1744243 TI - Prefrontostriatal connections in relation to cortical architectonic organization in rhesus monkeys. AB - Prefrontostriatal connections were investigated in rhesus monkeys using the autoradiographic technique to examine whether there are systematic relationships with regard to the architectonic organization of the prefrontal cortex. On the basis of progressive laminar elaboration, the different regions of the prefrontal cortex can be grouped into two architectonic trends. The dorsal trend, which begins in the medial proisocortical areas, can be followed through the dorsolateral prefrontal cortex, culminating in the dorsal arcuate region. The ventral trend, which originates in the orbital proisocortex, can be traced through the inferior prefrontal convexity to the ventral arcuate region. The results show that the main connections from the prefrontal cortex to the striatum are to the head and body of the caudate nucleus. These connections are topographically organized. Medial and dorsal prefrontal areas project predominantly to the dorsal and central portion of the head and body of the caudate nucleus, whereas orbital and inferior prefrontal areas are related mainly to the ventral and central portion. Moreover, prefrontostriatal connections have a medial-lateral topography. Medial and orbital prefrontal areas project medially in the head and body of the caudate nucleus, whereas the dorsal and ventral arcuate regions project laterally, adjacent to the internal capsule. The prefrontal regions above and below the principal sulcus project mainly to the intermediate sector of the head and body of the nucleus. However, there appears to be some degree of overlap of corticostriatal projections from the dorsal and ventral prefrontal regions, as well as within each trend. Relatively minor projections are directed to the putamen as well as to the tail of the caudate nucleus from certain subregions of the prefrontal cortex. Thus the distribution of prefrontostriatal connections seems to reflect the architectonic organization of the prefrontal cortex. Possible functional aspects of prefrontostriatal connectivity are considered in the light of behavioral and physiological studies. PMID- 1744244 TI - Superior paraolivary nucleus in the pigmented guinea pig: separate classes of neurons project to the inferior colliculus and the cochlear nucleus. AB - The superior paraolivary nucleus is a large component of the superior olivary complex in rodents and a major source of input to the inferior colliculi and the cochlear nuclei. In the present study, retrograde transport of the fluorescent tracers Fluoro-Gold, Fluoro-Ruby (tetramethyl rhodamine conjugated to dextran), fluorescein-coated microspheres, and Fast Blue were used to reveal the morphology and collateral projection patterns of cells in the superior paraolivary nucleus. The ascending projections to the inferior colliculus from the superior paraolivary nucleus arise mainly from round, multipolar cells, including large cells that project exclusively to the inferior colliculi and not to the cochlear nuclei. Projections to the ipsilateral and contralateral inferior colliculi arise from cells with similar morphology and, in fact, many of the cells that project contralaterally project ipsilaterally as well. Projections to the ipsilateral and contralateral cochlear nuclei arise primarily from cells that do not have collicular projections. On average, the somas of these cells are significantly smaller and more elongated than those that project to the inferior colliculi. Overlap between these ascending and descending systems is restricted to a small percentage of cells that send collateral projections to both the ipsilateral cochlear nucleus and the ipsilateral inferior colliculus. These cells are small and moderately elongated. Thus the ascending and descending projections examined here arise largely from different cells that belong to different morphological classes. PMID- 1744245 TI - Sexual dimorphism of the anterior commissure and massa intermedia of the human brain. AB - Neuroanatomical sex differences were observed in the midsagittal area of both the anterior commissure and the massa intermedia on analysis of postmortem tissue from 100 age-matched male and female individuals. The anterior commissure, a fiber tract whose axons in primates primarily connect the two temporal lobes, was an average of 12%, or 1.17 mm2 larger in females than in males. The massa intermedia, a structure that crosses the third ventricle between the two thalami, was present in 78% of the females and 68% of the males. Among subjects with a massa intermedia, the structure was an average of 53.3% or 17.5 mm2 larger in females than in males. Inclusive of subjects with and without a massa intermedia, this structure was a mean of 76% or 16.93 mm2 greater in females than in males. These sex differences were present despite the fact that the brains of males were larger than those of females. Since a majority of subjects were adults, it is unknown when sexual differentiation occurred. Anatomical sex differences in structures that connect the two cerebral hemispheres may, in part, underlie functional sex differences in cognitive function and cerebral lateralization. PMID- 1744246 TI - Effects of high fat diets on hibernation and adipose tissue in Turkish hamsters. AB - The effects of dietary fat saturation and fat content on hibernation and several properties of white and brown adipose tissue (WAT and BAT, respectively) were investigated in Turkish hamsters (Mesocricetus brandti). Male hamsters were housed in a long photoperiod (LD 16:8) at 23 degrees C and fed one of three diets: (1) chow (6.5% fat per weight), (2) chow + 13.5% vegetable oil (OIL, 20% fat per weight [largely unsaturated fat]) and (3) chow + 13.5% vegetable shortening [(SHORTENING, 20% fat per weight (largely saturated fat)]. Five weeks later body weights had stabilized and the animals were transferred to a short photoperiod (LD 8:16) at 3 degrees C. At the peak of the hibernation season (17 weeks) the animals were sacrificed within 24 h of arousal. Chow-fed hamsters had the greatest percentage of animals hibernating and days found torpid compared with the two fat-fed groups, with no differences found between the latter two groups for these measures. There were no differences between hibernating (HIB) and non-hibernating (NON-HIB) hamsters across or within the diet groups for any of the BAT measures [uncoupling protein content, mitochondrial mass, lipoprotein lipase (LPL) activity, and in vivo lipogenesis], nor were there significant effects of the diet on these measures. CHOW- and OIL-fed HIB hamsters showed decreases in body weight. All HIB groups had decreases in each carcass component, several fat pad weights, testes weight, and food intake. No consistent differences in WAT LPL activity or in vivo lipogenesis were found between HIB and NON-HIB hamsters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744247 TI - Isolation and characterization of parvalbumins from skeletal muscles of a tropical amphibian, Leptodactylus insularis. AB - Parvalbumins were isolated from skeletal muscles of a tropical amphibian, Leptodactylus insularis, and three new isotypes were identified. The total concentration of parvalbumins in L. insularis was the same as the total amounts found in an amphibian from the temperate or variable zone (Rana temporaria). Muscles of the thigh and foreleg had the maximum parvalbumin concentration (0.35 mmol.kg wet weight-1). Samples from pectoralis and rectus abdominis muscles had significantly less (0.29 mmol.kg-1). Three previously unknown parvalbumin isotypes (IV, IIIa, and IIIb) were isolated from the tropical amphibian. They were different from the isotypes (IVa and IVb) predominant in R. temporaria skeletal muscle. Parvalbumins are thought to have a role in the short-term removal of myoplasmic Ca2+ during muscle relaxation. Hence, the unique isotypes in L. insularis may reflect optimal molecular adaptations retained during the animal's evolution in a constantly warm environment. PMID- 1744248 TI - Purification and characterization of sulfatases from Haliotis rufescens: evidence for changes in synthesis and heterogeneity during development. AB - The digestive glands of many marine molluscs are rich sources of arylsulfatase enzymes which may function in the catabolism of sulfated polysaccharides in the diets of herbivorous species. Arylsulfatases, partially purified from the hepatopancreas of the red abalone, Haliotis rufescens, were investigated with respect to heterogeneity, catalytic requirements, and timing of induction during development. Four hepatopancreatic enzymes were purified from adult animals using a combination of hydrophobic interaction and anion-exchange chromatography. Zymograms of the four partially-purified enzymes produced by electrophoresis under nondenaturing conditions revealed a fifth, relatively more basic isozyme. All four partially-purified enzymes appear to be monomeric, with molecular weights of approximately 43,000 Da each, as measured by gel filtration. The affinities for p-nitrocatechol sulfate, pH optima, and strengths of inhibition by anions displayed by these enzymes are similar to the values reported for other molluscan arylsulfatases. Three of the four enzymes have Km values between 0.8 and 2.0 mM for p-nitrocatechol sulfate; the remaining enzyme (A2) has a Km of 6.7 mM. All four enzymes have pH and temperature optima of 5.5 and 45 degrees C, respectively. Three of the four enzymes have-t 1/2 (50 degrees C) values of 3.5 min; the enzyme A4 has a t 1/2 (50 degrees C) of 8.5 min. A monoclonal antibody directed against form A1b does not cross react with any of the other hepatopancreatic arylsulfatases when assayed by Western blot, confirming the structural heterogeneity of the adult enzymes. Total arylsulfatase activity increases in a biphasic manner during early abalone development, with the first increase occurring early in larval maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744249 TI - Role of transferrin in iron uptake by the brain: a comparative study. AB - The role of specific transferrin (Tf) and Tf receptor interaction on brain capillary endothelial cells in iron transport from the plasma to the brain was investigated by using Tf from several species of animals labeled with 59Fe and 125I, and 15-day and adult rats. The rate of iron transfer was much greater in the 15-day rats. It was greatest with Tf from the mammals, rat, rabbit and human, but much lower with chicken ovotransferrin and quokka (a marsupial), toad, lizard, crocodile, and fish Tf. The uptake of Tf by the brain showed a similar pattern, except for a very high uptake of ovotransferrin (ovoTf). Iron uptake by the femurs (a source of bone marrow) was also high with Tf from the mammalian species and low with the other types of Tf, but showed little change with aging of the animals. It is concluded that iron transport into the brain is dependent on the function of Tf receptors, probably on capillary endothelial cells, and that these receptors show the same type of species specificity as the receptors on immature erythroid cells. Also, the decrease in iron uptake by the brain as rats age from 15 days to adulthood is specific for the brain and is not a general effect of the aging process. PMID- 1744250 TI - Effects of six trace metals on calcium fluxes in brown trout (Salmo trutta L.) in soft water. AB - Calcium fluxes were measured simultaneously in brown trout fry maintained in an artificial soft water medium of [Ca] 20 mumol.1(-1) and pH 5.6, and exposed to each of six trace metals (Al, Cu, Fe, Ni, Pb, and Zn). The trace metal concentrations represented typical and maximum levels found in acid waters experiencing declining fishery status. In the absence of trace metals, evidence is presented which suggests that ca. 91% of Ca taken up from the external medium was by extraintestinal active transport. Calcium efflux was stimulated by both concentrations of Al, Cu, Fe, and Pb. Efflux was also stimulated by [Ni] 170 nmol.1(-1) and [Zn] 3000 nmol.1(-1). In some cases, response to increased efflux was stimulation of influx. Lack of stimulation of influx resulted in negative net Ca fluxes. Net Ca losses were recorded at both concentrations of Al, Pb, and Ni, lower concentrations only of Fe, and higher concentrations only of Cu and Zn. PMID- 1744251 TI - Differences in the hypoxic contraction of small isolated pulmonary arteries of cat and rabbit. AB - In small (less than 300 microns diameter) pulmonary arterial (PA) rings isolated from the cat, hypoxia induced a transient contraction (250 +/- 120 mg, n = 7), whereas in rings of rabbit PA of the same size, hypoxia had no significant effect (n = 19). Precontraction by 40 mmol KCl.1(-1), noradrenaline (NA) 10(-6) mol.1( 1), or histamine (His 10(-5) mol.1(-1)) did not modify this difference between the two species and did not potentiate the hypoxic contraction of small rings of the cat PA. Large rabbit pulmonary arterial segments (300-2000 microns) exhibited no response to hypoxia before precontraction (n = 15). In the presence of procaine (2%) rabbit PA rings (n = 6, small) exhibited no hypoxic contraction. These results in vitro reflect previous in vivo observations. PMID- 1744252 TI - Condoms and coitus: adolescents attitudes to AIDS and safe sex behavior. AB - This study investigated the relationship between sexual risk taking and attitudes to AIDS precautions among a sample of approximately 1000 non-virgin adolescents attending 15 colleges and universities in Victoria, Australia. Four attitudinal dimensions were isolated: Antiprecautions, Risk Denial, Abrogation of Responsibility and Fatalism. These attitudes showed meaningful relationships with different types of sexual risk: risk with a casual partner, risk with a regular partner, and multiple partnering. Different patterns of association emerged for males and females, with female risk behavior being more strongly related to antiprecautions attitudes. These differences were discussed in the light of gender-stereotypic responses to sexual situations, and their implications for educational interventions were explored. PMID- 1744253 TI - AIDS knowledge and beliefs, and sexual behavior of sexually delinquent and non delinquent (runaway) adolescents. AB - This study assessed general knowledge of AIDS, beliefs about preventing AIDS, and sexual behavior among two groups of male adolescents at high risk of HIV/AIDS: 60 sexually delinquent males and 57 non-delinquent runaway males. Significantly fewer sexually delinquent than non-delinquent (runaway) males had experienced sexual intercourse with a consenting female partner (45 vs. 89 per cent). Sexually delinquent youths scored significantly lower than non-delinquent youths in general knowledge of AIDS (65 vs. 73 per cent) and were not able to discriminate safer behaviors from those which were less safe (42 vs. 71 per cent). Both groups reported moderate support for beliefs about preventing AIDS. These results suggest HIV/AIDS prevention programs that attempt to increase knowledge are needed by these youths, particularly for sexually delinquent youths. PMID- 1744254 TI - Young offenders and alcohol-related crime: what interventions will address the issues? AB - Although most young offenders will grow out of both drinking and crime, interventions aimed at reducing crime through reducing drinking or reducing drinking so as to reduce health and social problems are important for some offenders. Where the aim is to reduce crime by reducing drinking, it is essential to assess carefully the relationship between the two in each person to ensure that this is logical. Since most adolescents drink and since controlled drinking is achievable by younger people with fewer alcohol-related problems, moderation rather than abstinence is a realistic goal for most young offenders. Behavioural self-control training is one type of intervention which can effectively encourage moderate drinking, but this has to be conducted in ways that will engage young offenders' interest, for example through self-help manuals, developing peer interventions and using simulated bar settings. In addressing the questions of which types of people commit which types of crime and what part alcohol plays in setting the conditions for crime to occur, studying the effects that young offenders expect alcohol to have under various conditions may contribute to the development of cognition modification components of interventions and enable better matching of clients with programmes. PMID- 1744255 TI - A metacognitive analysis of decision making in adolescence. AB - Samples of 43 early (CA = 13 years) and 41 middle (CA = 15 years) adolescents were compared on three categories of metacognitive knowledge as they relate to decision making--person knowledge, task knowledge and strategy knowledge. Metacognitive knowledge was assessed using a 19-item questionnaire. Consistent with our hypothesis, middle adolescents showed significantly greater metacognitive knowledge than early adolescents on all three scales. Self-reported decision making style (using the Flinders Adolescent Decision Making Questionnaire) and decision making performance on a hypothetical scenario were also measured. Middle adolescents reported a more competent decision making style than early adolescents, while group differences on the scenario were not found. Adolescents completing the scenario scored significantly higher on all measures of decision making metacognition. Significant correlations were found between metacognitive knowledge of decision making, self-reported decision making style and performance on the decision scenario task. By middle adolescence understanding of what is involved in the activity of decision making is well developed. This growth in understanding, accompanied by changes in social domains, plays a part in decision execution and style. PMID- 1744256 TI - Family relationship patterns: perceptions of teenage mothers and their non-mother peers. AB - Perceptions of self and family members were determined at two time periods for a sample of 30 teenage mothers and 30 non-mothers using the Family Relations Inventory and a family map exercise. Both at present and from childhood reminiscences, teen mothers perceived their mothers and sisters more positively than did non-mothers; fathers and brothers of the adolescent mothers were viewed more negatively than were those of the non-mothers. Results are discussed in light of prior explanations of adolescent motherhood with respect to family dynamics. An approach to intervention is suggested. PMID- 1744257 TI - Leisure activities of adolescent school students: predictors of participation and interest. AB - Frequency of participation and levels of interest in more than 60 leisure pursuits were measured via a questionnaire administered to 1248 adolescent high school students. The relationship between participation and levels of interest was measured by correlation as well as by asking the students to nominate up to three activities they would like to participate in but cannot and to indicate the reason for their non-participation. Factor analyses reduced the Participation and Interest items to six factors each. Multiple regressions were then conducted on the derived factor-score variables. Sex was the major predictor of participation in sports and vocational activities and of interest in sporting and gregarious activities. Age, school location, ethnicity and SES were lesser predictors for groups of activities such as the social and outdoor pursuits. The results are discussed in terms of the theoretical and practical implications of the relationship between participation and interest as well as the prediction of participation and interest levels by developmental and social factors. PMID- 1744258 TI - Production of proteases by psychrotrophic microorganisms. AB - Six milk-derived psychrotrophic microbial cultures were screened for the ability to grow at refrigerated temperatures and produce proteases in reconstituted skim milk. Of these, two cultures, Pseudomonas fluorescens M3/6 and Pseudomonas fragi K122, produced extracellular protease(s) beginning 7 d postinoculation when the cultures had entered late log or early stationary phases of growth. Further work with these two cultures showed that intracellular proteases were present after only 20-h incubation, before detection of the extracellular proteases. Using H-D valyl-L-leucyl-L-lysyl-4-nitroanilide (S-2251), a sensitive substrate for plasmin activity, P. fluorescens was shown to have greater intracellular proteolytic activity than extracellular activity at 20 h of incubation. The intracellular enzyme activity remained constant while the extracellular and periplasmic activities increased over the remaining 6-d incubation period. The proteases in crude extracellular extracts from both cultures were characterized and were heat stable with broad temperature (7 to 52 degrees C) and pH (pH 5.5 to 8.5) ranges for activity and were inhibited by the metal chelator, EDTA, indicating that they were metalloproteases. PMID- 1744259 TI - Microbiological analysis and starter culture growth in retentates. AB - Pasteurized skim milk was concentrated by UF to 2-, 4-, and 5-fold. The retentates were evaluated for microbiological quality, heat treatments to inactivate microorganisms, and lactic acid bacterial starter culture activity. Aerobic mesophilic bacterial counts in raw milk decreased from an initial 1.4 x 10(6) to 3.9 x 10(2) cfu/ml after pasteurization. During UF, counts increased from 3.9 x 10(2) cfu/ml UF, counts increased from 3.9 x 10(2) cfu/ml in pasteurized milk to 1.4 x 10(3), 1.4 x 10(4), and 1.8 x 10(4) cfu/ml in 2-, 4- and 5-fold retentates, respectively. Psychrotrophic bacterial counts decreased from 9.9 x 10(5) cfu/ml in raw milk to 3.7 x 10(1) cfu/ml in pasteurized milk and gradually increased to 1.0 x 10(2), 2.5 x 10(2), and 1.4 x 10(3) cfu/ml in 2-, 4 , and 5-fold retentates, respectively. Thermophilic bacterial counts remained less than 10 cfu/ml in all samples. Skim milk and retentates inoculated with five starter cultures at 1% failed to decrease the pH below 4.6 in (2-, 4- and 5 fold). The 4- and 5-fold retentates inoculated with Lactococcus lactis spp. cremoris or Lactococcus lactis spp. lactis cultures were partially coagulated with pH greater than 5.6. In general, the pH of retentates remained higher than that of skim milk. Clotting of uninoculated samples was observed, and a spore forming contaminant, tentatively characterized as Bacillus cereus and capable of clotting milk at a pH greater than 6, was isolated from the clotted samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744260 TI - Quantification of alpha s1-casein in goat milk from French-Alpine and Anglo Nubian breeds using reversed-phase high performance liquid chromatography. AB - Samples of isoelectrically precipitated goat casein from the milks of French Alpine and Anglo-Nubian breeds were separated into four components in a single run by reversed-phase HPLC. The proportion of alpha s1-casein thus resolved was determined quantitatively. The method uses a reversed-phase C-4 column and a linear gradient from 30 to 50% acetonitrile in 30 min with trifluoroacetic acid constant at .1%. Sodium dodecyl sulfate-PAGE was carried out to establish the identity of the isolated components. By a comparison with previously published results for caprine and bovine milk caseins, the four peaks were identified as kappa-, alpha s2-, alpha s1-, and beta-casein. Quantitative variations in the chromatographically resolved alpha s1-casein fraction of goat milk were evident. Some individual goat milks contained high levels of alpha s1-casein (2.70 g/L), but others contained significantly low levels (.12 g/L). There was no statistical difference in the overall means between breeds in alpha s1-casein composition, but cluster analysis statistics showed three distinct categories of alpha s1 producers: high, medium, and low. Interestingly, 6 of 15 French-Alpine goats and only one Anglo-Nubian goat fell into the "low" producer category (.38 +/- .2 g/L). Thus, expression of the alpha s1-component may be genetically regulated but may not be a breed-specific trait. PMID- 1744261 TI - Separation of beta-casein A1, A2, and B using cation-exchange fast protein liquid chromatography. AB - beta-Casein genetic variants A1, A2, and B were separated using cation-exchange fast protein liquid chromatography. beta-Casein from a herd bulk casein sample eluted as a series of three peaks. Casein samples from individual cows containing known combinations of beta-casein A1, A2, and B were used to confirm that the three peaks were beta-casein genetic variants. An acid-PAGE gel confirmed the identity of the peaks that eluted from the column. PMID- 1744262 TI - Association of kappa-casein glycosylation with milk production and composition in Holsteins. AB - A total of 545 milk samples were collected from 53 Holstein cows for 1 yr. On test day, morning milk yields were recorded; milk samples were analyzed for N acetylneuraminic acid, protein, fat, casein, kappa-casein, and SCC. the relationship between the degree of glycosylation of kappa-casein and morning milk yield and composition was investigated. Data were analyzed using least squares procedures with a model that included test day, parity, stage of lactation, SCC, and phenotype for kappa-casein as fixed effects and N-acetylneuraminic acid content of kappa-casein as covariate. After adjustments were made for effects of environmental and genetic factors, the degree of glycosylation of kappa-casein was associated with morning milk yield, protein, and casein content. Milk yield increased linearly with an increase of N-acetylneuraminic content up to approximately 70 micrograms/mg of kappa-casein. PMID- 1744263 TI - Relative buffering capacity of goat milk, cow milk, soy-based infant formulas and commercial nonprescription antacid drugs. AB - Buffering capacities of goat milk (Alpine, Nubian), cow milk (Holstein, Jersey), soy-based infant formulas, and non-prescription antacid drugs were estimated. Total N, protein, NPN, and P2O5 as major buffering entities were quantified for each milk category. Nubian goat milk had the highest levels of the three major buffering chemical entities, and the infant formulas contained less total N and NPN compared with natural goat and cow milks. Buffering capacities of the formulas also were lower than those of natural milks. Combinations of milk and antacid drugs had higher buffering capacities than either the milk or drug alone. Drug plus goat milk combinations upon addition of more than 2 ml of acid titrant exhibited fewer changes in pH than the respective drug plus cow milk combinations. PMID- 1744264 TI - Comparison between lactoferrin and subepithelial matrix protein binding in Staphylococcus aureus associated with bovine mastitis. AB - Staphylococcus aureus strains (n = 100) isolated from bovine mastitis were classified according to the presence of capsular polysaccharide serotype 5 (n = 46), type 8 (n = 26), and non-5/8 (n = 28). Strains from each type were tested for protein interaction in a 125I-labeled ligand binding assay. A majority of type 5 and type 8 strains showed a higher degree of binding to lactoferrin, fibronectin, and IgG than the non-5/8 strains. Fibrinogen binding was low in all serotypes. Most of the type 5 and non-5/8 strains bound less than 10% laminin, whereas type 8 strains bound laminin in the 11 to 20% range. Non-5/8 strains significantly differed from type 5 in lactoferrin, fibronectin, fibrinogen, and IgG and also from type 8 in fibrinogen and IgG binding. The differences in protein binding between type 5 and type 8 were nonsignificant. The degree of lactoferrin binding in all types positively correlated with laminin binding. Lactoferrin and fibrinogen bindings were correlated in type 5 and type 8 strains. Lactoferrin and fibronectin bindings were correlated only in type 5 strains. These data suggest that bovine lactoferrin binding is common and associated with subepithelial matrix protein interactions in certain serotypes of S. aureus. PMID- 1744265 TI - Effect of anticapsular antibodies on neutrophil phagocytosis of Staphylococcus aureus. AB - One of the major virulence factors of Staphylococcus aureus is development of an exopolysaccharide capsule in vivo, which inhibits recognition of antibodies to highly antigenic cell wall by neutrophils. To circumvent this inhibition, an attempt was made to produce anticapsular antibodies. Three cows per group were immunized in midlactation by injections in the area of the supramammary lymph node and intramuscularly and were boosted on d 14, 42, and 70 with three variants of Smith S. aureus: compact, unencapsulated; diffuse, rigid capsule; and diffuse large clearing, exceptionally large flaccid capsule using dextran sulfate as adjuvant. Serum agglutination and ELISA titers of cows immunized with diffuse and diffuse large clearing increased after immunization and after each boost and remained elevated to the end of the experiment at 112 d. Phagocytosis of diffuse and diffuse large clearing, measured by flow cytometry, was enhanced by immunization with either organism. No antibody response to capsule or enhanced phagocytosis of diffuse developed in cows immunized with compact. However, anticompact antibodies were opsonic for diffuse large clearing. These data show that bovine antibodies to S. aureus capsule are opsonic for bovine neutrophils and that capsule plays a role in inhibition of cell-wall opsonization of S. aureus. PMID- 1744266 TI - Antibacterial activity of bovine mammary gland lymphocytes following treatment with interleukin-2. AB - The antibacterial characteristics of bovine mammary gland lymphocytes were evaluated following in vitro activation with recombinant human interleukin-2. Mammary gland effector cell populations were prepared by enzymatic digestion of mammary tissue followed by centrifugation through a discontinuous Percoll gradient. Functional activity of cells cultured for 48 h with or without interleukin-2 were evaluated by direct cytotoxicity using K562 target cells and by antibacterial activity against Staphylococcus aureus. Cytotoxic activity of interleukin-2-treated mammary gland lymphocytes was enhanced compared with control cultures, which exhibited no cytotoxic capabilities following 48 h of culture. Bactericidal activity also was elevated in cells cultured in interleukin 2-supplemented media. Enhanced expression of major histocompatability complex class II molecules on the surface of interleukin-2-treated lymphocytes was associated with the higher level of cell activation. Phenotypic analyses of the recovered population showed that the majority of cells were lymphocytes bearing CD2 molecules. It may be possible to activate these effector cell populations in vivo and increase resistance of the mammary gland to bacterial infections in a nonspecific manner. PMID- 1744267 TI - Efficacy of a cephapirin dry cow product for treatment of experimentally induced Staphylococcus aureus mastitis in heifers. AB - A dry cow product containing 300 mg of cephapirin benzathine was evaluated in pregnant and nonpregnant Jersey heifers for its effect on experimentally induced Staphylococcus aureus mastitis. Cephapirin was detectable in mammary secretion of nonpregnant heifers for up to 5 wk and in tissue for 1 wk after intramammary infusion. Staphylococcus aureus was not detectable in tissue and secretion of treated quarters at 1 and 3 wk but was not eliminated from two quarters of one heifer tested at 6 wk posttreatment. Histologic evaluation of mammary tissue from nonpregnant heifers revealed significant differences in leukocytosis between uninfected and S. aureus-infected quarters but no differences in epithelium, lumen, and stroma, indicating no difference in secretion potential or glandular development. Twenty-five pregnant Jersey heifers were experimentally infected in two quarters with S. aureus 12 to 14 wk prepartum. After 1 to 3 wk, 13 heifers were infused in 21 S. aureus-infected quarters with a commercial cephapirin dry cow product. Nine infected quarters were left untreated. All treated quarters were bacteriologically negative both at calving and through 2 mo after calving. Of the 9 infected quarters not treated prepartum, 1 spontaneously cured and 2 became non-functional. The remaining quarters were treated at calving with a commercial cephapirin lactating cow product. Of these, 3 cured and 3 failed to resolve. PMID- 1744268 TI - Histological response of the bovine mammary gland to intramammary devices. AB - Histologic response of the bovine mammary gland to presence of three intramammary device models (abraded, star, or grooved) was studied in 12 lactating cows. Uninfected quarters fitted with devices exhibited greater leukocyte infiltration into teat and gland cistem linings as well as into mammary parenchyma adjacent to the gland cistem compared with unfitted control quarters. Cytologic alterations to cistem linings in device-fitted quarters ranged from degeneration and sloughing of surface cells of the double-layered epithelium to hyperplasia, stratification, and keratin formation. In uninfected quarters, quantification of mammary parenchymal components showed no differences among models for percentages of epithelium, but percentage of lumen was lowest and stroma highest for the star intramammary device model, suggesting reduced secretory activity or mammary involution in response to these intramammary devices. Presence of bacterial infection amplified the histologic responses to all devices. Leukocyte infiltration remained greater in device-fitted quarters compared with controls but was elevated over uninfected quarters for all treatments. Likewise, hyperplasia, stratification, and keratin formation of the cistem epithelial lining were more frequently observed in infected quarters. Among models in infected quarters, percentage of lumen was lowest and stroma highest in quarters fitted with abraded devices. In most cases, presence of infection masked any effect of devices on mammary parenchymal components. Plaque formation was observed on all models and tended to be thicker on those retrieved from infected quarters. Electron microscopic examination showed that plaque was composed of leukocytes, cell debris, keratin, and amorphous material. Results demonstrated that most intramammary device models were successful in stimulating leukocytosis into the gland, and tissues from fitted quarters displayed alterations to cisternal linings; however, quarters fitted with these devices exhibited reduced secretory activity. PMID- 1744269 TI - Analysis of somatic cell count data by a peak evaluation algorithm to determine inflammation events. AB - Increases in SCC are an expression of inflammation events in the udder. Inflammation events are sporadic, of variable amplitude and duration, and can be analyzed by computer programs designed to evaluate pulses of hormone secretion. Baseline values for SCC, which take into account long-term trends, were calculated using the PULSAR peak evaluation algorithm. An inflammation event was defined as an increase of log2(SCC) of at least 1 unit from the preceding data point if the observed value exceeded the baseline value by a threshold value. Incidence rate, duration, and amplitude of inflammation events were calculated. Weekly composite milk SCC from individual cows from two Florida dairy farms were recorded. Data were analyzed for effects of season (summer and fall) and bST in two separate data sets. Incidence rate of inflammation events was higher in summer than in fall (4.31 and 2.91 events per cow x year). In one of two data sets only, duration of inflammation events was longer in cows treated with bST (2.4 +/- .2 vs. 1.6 +/- .2 wk). In contrast, least squares analysis of variance of log2(SCC) did not detect differences due to season or bST. The use of the peak evaluation algorithm led to the detection of seasonal and bST effects on inflammation events in cows. PMID- 1744270 TI - Reduced lactational performance following intravenous endotoxin administration to dairy cows. AB - Nonpregnant lactating cows were given 100 micrograms of endotoxin via the jugular vein to determine effects of intravenous endotoxin administration on mammary inflammation and lactational performance. At the first milking (11 h) posttreatment, milk yield was reduced 33%. Milk fat percentage was elevated at this time, but lactose concentration was decreased. Milk yield and composition returned to pretreatment levels within 2 d. Clinical mastitis was not induced by endotoxin treatment, but milk SCC, NAGase, serum albumin, and lactoferrin were increased by 50%. This increase was small compared with increases during mastitis and may have resulted from lower milk volume. These results support the hypothesis that part of the reduced lactational performance during endotoxin mastitis is mediated by systemic pathophysiological responses and indicate that intravenous endotoxin administration may be a useful model to study adverse effects of infectious disease on lactational performance. PMID- 1744271 TI - The influence of insulin and amino acid supply on amino acid uptake by the lactating bovine mammary gland. AB - Four lactating dairy cows received arterial infusions of insulin (1.41 U/h), an AA mixture (threonine, methionine, leucine, phenylalanine, and lysine at 5.87, 1.90, 3.55, 2.17, and 4.21 mmol/h, respectively), and a combination of the two in a 4 x 4 Latin square. The infusions were performed over a 3-d period directly into the extra pudic artery on both sides of the mammary gland, and samples were taken simultaneously of the downstream extra pudic arterial blood and also of subcutaneous abdominal venous blood. Blood flow was measured by dye dilution using p-amino-hippuric acid and was increased by 37% by infusion of insulin plus AA (P less than .05). Infusions of AA tended to increase the arteriovenous difference and uptake of the infused AA (P less than .05 for phenylalanine) and had varying effects on the uninfused AA. Inclusion of insulin in the AA infusion tended to increase uptake of infused AA, whereas infusions of insulin alone tended to decrease uptake. There were no significant effects of infusion on milk yield or composition. PMID- 1744272 TI - Comparison of somatotropin and growth hormone-releasing factor on milk yield, serum hormones, and energy status. AB - Holstein cows received 12 mg/d of growth hormone-releasing factor (continuous i.v. infusion, n = 5), 14 mg/d of bST (single daily i.m. injection, n = 8), or no treatment (controls, n = 8) for 60 d. Compared with controls (31.6 kg/d), bST and growth hormone-releasing factor increased milk yield to 34.2 and 37.0 kg/d, respectively. The increase in milk yield induced by the growth hormone-releasing factor was greater than that for bST. Milk yield was not different among groups following cessation of treatment. Milk energy output was 24.2 Mcal/d in controls, and growth hormone-releasing factor increased milk energy output to 28.5 Mcal/d. Milk energy output of cows receiving bST was 26.1 Mcal/d. Growth hormone releasing factor increased DMI (23.2 kg/d) over that of controls (21.1 kg/d), whereas bST (21.5 kg/d) did not. Relative to controls, bST increased averaged daily serum somatotropin from 1.3 to 7.6 ng/ml and insulin-like growth factor-I from 67.5 to 116.0 ng/ml. Relative to bST, growth hormone-releasing factor increased serum somatotropin to 16.3 ng/ml and insulin-like growth factor-I to 202.6 ng/ml. Relative to control (115.8 meq/dl) and bST (158.1 meq/dl), growth hormone-releasing factor increased plasma NEFA (230.3 meq/dl). During treatment, calculated energy balance was negative for cows receiving growth hormone releasing factor but positive for bST and control cows. Milk composition, body condition score, BW, and apparent digestibility of DM were not different among treatments. We conclude that i.v. infusion of 12 mg/d mg of growth hormone releasing factor has greater galactopoietic activity than i.m. injections of 14 mg/d of bST.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744273 TI - Postparturient metabolic and production responses in cows previously exposed to long-term treatment with somatotropin. AB - Postparturient metabolic and production responses were studied for 85 multiparous cows consisting of controls and animals that had been previously exposed to long term treatment with bST. Older cows previously exposed to bST at high doses (51.6 mg/d) had lower milk yields than controls. However, there were no significant differences compared with controls in milk yield for lower dose (17.2 mg/d) older cows or parity 2 cow groups. The bST-treated groups had higher postpartum DMI, lower serum FFA, lower serum beta-hydroxybutyrate levels, and higher serum glucose than controls. Some bST-exposed groups had lower milk fat but higher milk protein levels. All bST-treated groups had significantly lower ratios of C18 to C4 to 10 milk fatty acids. Control cows of both parity groups were in higher body condition and weighed more than bST-treated cows prior to calving. The differences in postpartum metabolism may be attributed to differences in body composition resulting from bST treatment in the prior lactation, because use of body condition score prior to calving as a covariate did not substantially alter responses. The control cows probably had greater reserves of mobilizable lipid. These contentions are supported by changes in milk composition for bST-treated cows, which were consistent with animals of greater appetite, mobilizing less lipid. The bST-treated cows were probably more energetically efficient milk producers because they produced milk from feed rather than from mobilization of tissue stores. These data suggest that bST use in a prior lactation may have potential benefit in reducing risk of metabolic disorders associated with lipid mobilization in the postparturient period. PMID- 1744274 TI - Expert system for evaluation of reproductive performance and management. AB - A microcomputer expert system for dairy herd reproductive management was developed using an expert system shell and Turbo Pascal. The expert system initially examines the broad areas of days open, days to first breeding, detection of estrus, and conception rate to determine whether a problem exists. Interpretations ranging from "excellent" to "severe" were established for each trait. The system then selects an area for evaluation that has the largest negative influence on days open. Once an area has been selected for further evaluation, the expert system utilizes information from the user and DHI reports developed by the Dairy Records Processing Center in Raleigh, NC. These reports identify problems with conception categorized by production, parity, service number, days in milk, breed, and service sire. In addition, questions are presented by the expert system to isolate problems of accuracy of data, use of natural service, semen handling, AI technique, detection of estrus, signs of estrus, and other management areas. Recommendations and suggestions are given. Ten commercial herds having a conception rate less than 40% were evaluated by the expert system and by an extension reproduction specialist who supplied information for the system. Of 100 areas investigated, the expert system and extension specialist identified 47 as potential problem areas, agreeing on 85% of them. Most discrepancies resulted from the specialist applying a less restrictive standard when values were close to a preselected threshold. PMID- 1744275 TI - Evaluation of uterine body and bilateral uterine horn insemination techniques. AB - Uterine body and bilateral horn insemination techniques were compared in 364 Jersey cows and 138 heifers by two inseminators. For horn inseminations, approximately one-half of the semen was placed in left uterine horn just prior to the point of resistance. The remainder of semen was then placed in the right uterine horn just prior to the point of resistance. Animals were inseminated in the uterine body on even days of the month throughout the study. On odd days of the month, animals were inseminated in both uterine horns. A total of 62.9% of 286 animals inseminated in the uterine body were pregnant versus 54.2% of 216 animals inseminated in both uterine horns. Differences were greater for cows than for heifers and at first and second services than at third or greater services. These results favor current recommended techniques to deposit semen into the uterine body correctly. PMID- 1744276 TI - Iron sulfate and feed pelleting to detoxify free gossypol in cottonseed diets for dairy cattle. AB - Thirty-two lactating cows were fed ad libitum diets with 1) 18.7% soybean meal, 2) diet 1 plus 500 ppm supplemental Fe from FeSO4.H2O, 3) 15% whole cottonseed, or 4) diet 3 plus 500 ppm Fe from FeSO4.H2O. Dry matter intakes were similar except for cows fed diet 2, which was lower. Cows fed whole cottonseed diets ingested 23 g/d of free gossypol per cow. Free gossypol apparently excreted was lower than its intake. Iron excretion was similar to Fe intake. Blood metabolites and productive performance did not differ among the diet groups. No signs of gossypol toxicity were observed. Twelve neonatal Holstein male calves were fed a commercial milk replacer for 4 wk, then were allowed ad libitum access to diets with 1) 27% soybean meal, 2) 50% whole cottonseed, or 3) diet 2 plus 500 ppm Fe from FeSO4.H2O. Dry matter intakes were similar but slightly lower for calves fed diet 3. Daily individual intakes of free gossypol from diets 2 and 3 were 2 g, which was lower than the expected 4 g due to an apparent effect of pelleting. Blood metabolites did not differ among the groups, and calves averaged about .6 kg of daily gain on these diets. A follow-up study showed that pelleting reduced free gossypol by as much as 70% in whole cottonseed and by 48% in cottonseed meal. Pelleting represents a mechanism to decrease the toxicity of gossypol in cottonseed products. PMID- 1744277 TI - Feeding supplemental fat and undegraded intake protein to early lactation dairy cows. AB - Forty-eight Holstein cows (16 primiparous) were fed alfalfa silage-based TMR containing 18% CP with 33 or 36% of the CP as undegraded intake protein and with 0 or 2.8% supplemental fat (DM basis). Expeller soybean meal replaced solvent soybean meal to vary undegraded intake protein, and sodium alginate-treated tallow was used as the fat source. A standard diet containing solvent soybean meal without fat was fed during the first 21 d postpartum for covariate adjustment of milk production. A continuous lactation design with 2 x 2 factorial arrangement of treatments was used with supplemental fat and undegraded intake protein as main effects. Feeding supplemental fat increased actual milk (32.9 vs. 31.7 kg/d) but decreased milk protein concentration. Cows fed supplemental fat also had higher BW, and weight gain was significant with time. Increasing undegraded intake protein did not affect milk yield, composition, or component yield. There were no significant interactions between supplemental fat and undegraded intake protein on milk yield or composition. Milk fatty acid composition was not altered by addition of undegraded intake protein, but C6 to C14 fatty acids were reduced by adding supplemental fat. Results do not support the strategy of increasing levels of undegraded intake protein when supplemental fat is fed. Variation in undegraded intake protein content of feed-stuffs appears to be of more importance in ration formulation than interactions between supplemental fat and protein. PMID- 1744278 TI - Lactational performance of high producing dairy cows fed diets containing salmon meal and urea. AB - Thirty Holstein cows were used in a 12-wk trial to study the effects of salmon meal and urea on lactational performance. Two experimental diets, one containing 5.6% salmon meal and the other 5.2% salmon meal plus .42% urea, were compared with a soybean meal control diet. Salmon meal and urea replaced a portion of the soybean meal. Dietary undegraded intake protein levels (expressed as percentage of CP) were 28.8, 35.6, and 32.4% for soybean meal, salmon meal, and salmon meal plus urea. Total mixed diets (average 17.3% CP, 17.6% ADF) consisting of 60% concentrate mixture and 40% bromegrass silage (DM basis) were fed twice daily. Total DMI was lower with salmon meal compared with soybean meal (20.2 versus 22.2 kg/d); salmon meal plus urea (21.2 kg/d) was intermediate. Actual milk production was similar for all diets (average 41.1 kg/d). Percentage milk fat and 4% FCM yield were lower with salmon meal (2.56%, 31.6 kg/d) and salmon meal plus urea (2.50%, 31.4 kg/d) than with soybean meal (3.03%, 35.9 kg/d). Gross efficiency (weight FCM/weight DMI) was higher for soybean meal than for salmon meal and salmon meal plus urea. Acetate: propionate tended to be higher with the soybean meal diet. The use of a high oil fish meal to provide a source of rumen undegraded intake protein, alone or in combination with urea, resulted in a decrease in milk fat percentage and yield without any beneficial effects on milk production or lactational efficiency. PMID- 1744279 TI - Effect of sometribove on rumen fermentation, rate of passage, digestibility, and milk production responses in dairy cows. AB - Six ruminally and duodenally fistulated Holstein cows 60 d postpartum were assigned randomly to each of two treatments in a single reversal design. Treatments consisted of placebo or 25 mg of sometribove (bST) injected daily. Treatments were initiated at 60 d +/- 7 postpartum and maintained for 6 wk with a 3-wk adjustment between treatment periods. All cows received a TMR consisting of 16% CP and 1.67 Mcal of NE I/kg of DM. Influence of bST on rumen fermentation characteristics, digesta rate of passage, apparent nutrient digestibility, and milk production was evaluated. Milk yield of treated animals was 4.0 kg/d higher than controls. The 3.5% FCM and milk production efficiency (3.5% FCM/DMI) were significantly higher in treated animals than in controls (29.0 vs. 25.4 kg/d and 1.38 vs. 1.21 kg/kg, respectively). Percentage of rumen cellulolytic bacteria (of total viable bacteria) was not significantly different for bST-treated animals (6.4 vs. 3.4%). Total number of rumen protozoa tended to be higher (7.25 vs. 6.55 x 10(3)/ml) in bST-treated animals. Ruminal percentages of CP, NH3 N, alpha-amino N, VFA, and pH were unaffected by treatment. Sometribove treatment did not significantly affect liquid dilution or solids turnover rates. Percentages of CP, alpha-amino N, and NH3 N content in duodenal samples were unaffected by treatment. Total tract apparent digestibility of nutrients and mean daily DMI were unaffected by treatment. PMID- 1744280 TI - Zinc absorption, metabolism, and endogenous excretion in zinc-deficient and normal calves over an extended time. AB - Zinc metabolism was studied in Zn-deficient and control Holstein calves over a 2 mo period following a single oral or i.v. 65Zn dose. In both orally and i.v. dosed animals, all gastrointestinal tissue sections from Zn-deficient animals contained more 65Zn than comparable tissues of controls. Contents of proximal small intestinal sections of Zn-deficient calves contained more 65Zn 8 to 10 wk after dosing than did those from controls; however, the reverse occurred in the distal small intestine, cecum, and large intestine. With both dosing methods, Zn deficient calves retained more 65Zn throughout the study. Daily 65Zn excretion rate as a percentage of that retained declined for 6 wk after dosing, indicating a constantly increasing biological half-life. For deficient calves, the biological half-life was about 500 d in the later weeks of the experiments. In orally dosed, Zn-deficient animals, specific activity of fecal 65Zn exceeded that of serum Zn throughout the study. This shows a shortcoming in the basic assumption of measuring endogenous Zn loss from fecal and serum specific activities and total fecal stable Zn. Thus, endogenously excreted Zn is not representative of that remaining. PMID- 1744281 TI - Estimation of genetic parameters using sampled data from populations undergoing selection. AB - In populations undergoing selection, genetic (co)variances may be altered in amounts dependent on selection intensity among parents and the mating structure. In order to estimate the genetic parameters of the unselected population, all information that led to the current population must be included in the analysis. This is often not possible due to missing information or computer limitations, and, therefore, only samples of data and pedigree information of recent generations are included in analysis, and simplified operational models are used. Biases in genetic parameters, which were estimated by multitrait derivative-free REML method, were investigated in different strategies of sampling data and pedigree. In dual purpose cattle, in which young bulls are selected for growth before being progeny tested for milk yield, heritabilities and additive genetic correlations were all unbiased when all data and all relationships were used in an animal model. Using only recent data but all relationships in an animal model also gave unbiased estimates of heritabilities. Using an animal model for growth but a sire model for milk with all data gave an unbiased estimate of heritability for milk. When only recent data were used, the heritability estimate for milk was biased downward. In single purpose dairy populations, sire models gave biased estimates of genetic parameters even when all data were included in the analysis. Treating sire effects on second crop of daughters as fixed did not overcome selection bias. PMID- 1744282 TI - The use of integer programming in dairy sire selection. AB - A computerized sire selection integer program, IPSIRE, was developed to test the optimality of solutions obtained by using MAXBULL, a popular computerized sire selection aid. The IPSIRE program uses an optimization software package and a compatible spreadsheet; MAXBULL uses linear programming techniques. The computer programs were compared using large and small data sets. Multiple combinations were run, varying the levels requested for PD fat percentage, PD type, and price paid per unit of semen. All other constraints were held constant. The objective function for all combinations maximized PD milk. The IPSIRE program exceeded MAXBULL by an average of $2.5 for PD dollars and 7.3 kg (16.1 lb) for PD milk using the small bull data base. Sire averages for traits PD type, PD fat percentage, and price paid were not different between the two programs. Similar trends were seen using the large bull data base. The IPSIRE program exceeded MAXBULL by an average of $1.2 for PD dollars and 4.1 kg (9.0 lb) for PD milk, whereas sire averages for PD fat percentage, PD type, and price paid were not different between programs. The goal for PD type had the least influence of the three goals on sire averages for PD milk. The goal for price paid had the greatest impact on realized PD milk; higher goals for price paid produced solutions with higher values for realized PD milk. The IPSIRE program required longer computational times for finding solutions that maximized PD milk than MAXBULL. PMID- 1744283 TI - Heritability of hypocalcemia at first parturition in Norwegian cattle: genetic correlations with yield and weight. AB - Minimum plasma calcium level around parturition and its relation to BW at parturition, milk yield, and weight change in mo 1 of lactation were studied in 334 first lactation Norwegian cows. Minimum plasma calcium level was reached 18 to 30 h postpartum. Single observations for all animals were fitted with a multitrait animal model including all genetic relationships. Heritabilities of the traits were calcium postpartum, .11; milk yield, .35; BW, .65; and weight change, .17 with standard errors about .10. Genetic correlations between calcium postpartum and the other traits were milk yield, -.49; BW, -.66; and weight change, .42 with standard errors about .25. Environmental factors with detectable effect on hypocalcemia were age at parturition and calving season. Regression of calcium postpartum on age was -2.66 x 10(-4) mmol/L per d. Calvings shortly after the pasture season were related to higher calcium postpartum than calvings after 3 to 4 mo with indoor feeding. PMID- 1744284 TI - Site of digestion of starch in the gastrointestinal tract of dairy cows and its effect on milk yield and composition. AB - Physical and chemical processing of feed ingredients and feeding management strategies are major instruments of manipulating amount and site of starch digestion in the gastrointestinal tract. Generally, as rumen escape of starch increases, postruminal starch digestion increases, and there does not appear to be a limitation to intestinal starch digestion. However, the efficiency with which postruminal starch is digested decreases, which represents a limitation that warrants investigation. Even though digestible dietary starch is presented to the intestine, there is no net glucose absorption at the portal vein, and plasma glucose levels remain relatively unaffected. This result may be associated with the large metabolic requirement for postruminally absorbed glucose, which is preferentially used for oxidative metabolism at the visceral tissue level. In addition, peripheral glucose concentration is highly regulated. A possible implication is that the exogenous glucose supply may spare endogenously synthesized glucose for gut metabolism, allowing more to be directed to the mammary gland. Amino acids also may be spared (less metabolism of dietary and tissue amino acids in the gut). Current production studies yield no clear evidence as to the benefits of postruminal digestion of starch to enhance milk yield or to change its composition. However, studies suggest that starch digested postruminally is used more efficiently for milk synthesis than that digested in the rumen. PMID- 1744285 TI - Balancing carbohydrates and proteins for optimum rumen microbial yield. AB - Establishing conditions under which rumen fermentation will be optimized requires an understanding of the nutrient requirements of the mixed microbial population. The major nutrients required by rumen microbes are carbohydrates and proteins, but the most suitable sources and quantities needed to support maximum growth have not been determined. Digestion of proteins results in the production of peptides, which can accumulate in the rumen. Peptides are further hydrolyzed to amino acids, some of which are deaminated, producing ammonia. Although peptides, amino acids, and ammonia all may individually serve as sources of N for various microbes, the total population achieves the highest growth rate on mixtures of all three sources. In a somewhat analogous manner, carbohydrates are digested by exoenzymes to oligosaccharides that are available for crossfeeding by the mixed microbial population. Based on data from both in vitro and in vivo studies, there is general agreement that rate of digestion of carbohydrates is the major factor controlling the energy available for microbial growth; in addition, rate of digestion of total carbohydrate is directly related to proportion of starches, pectins, and sugars. Proteins affect both total fermentation and production of microbial DM per unit of carbohydrate fermented. It appears that the quantity of ruminally available protein needed to optimize microbial growth may, under some conditions, be as high as 14 to 15% of diet DM. PMID- 1744286 TI - A theoretical model for understanding dentists' behavior in treating patients with AIDS. AB - This paper attempts to expand on a model from the theory of reasoned action to help us identify and better understand the reasons dentists do or do not treat dental patients with, or at risk for, AIDS. We propose in the model that the dentist's actual behavior in treating dental patients with, or at risk for, AIDS, in his or her practice is a function of both his or her intention to treat such patients and his or her nonvolitional factors relevant to the behavior. The dentist's intention to treat patients with AIDS or HIV infection, or those belonging to high risk groups, is influenced by two belief components: (1) attitudinal variables, which are the dentist's beliefs about the consequences of treating such patients and the value that these consequences have for him or her; and (2) normative variables, which indicate the dentist's perceptions of how his or her reference groups view the treatment of such patients in his or her practice and his or her motivation to comply with those views. Finally, both the two belief components and the nonvolitional factors are affected by the personal characteristics and the environmental variables. PMID- 1744287 TI - Factors that affect patient attitudes toward infection control measures. AB - This study examined how differences in infection control procedures and patients' perceived knowledge of infection control, and how AIDS and hepatitis might affect attitudes toward the use of such measures. Patients receiving treatment at two sites where the methods of infection control and the frequency of their use differed (dental school and private dental practices) were surveyed concerning their approval/acceptance of infection control measures and self-report of knowledge concerning infectious disease and possible transmission of infectious disease during dental treatment. Data were collected from 379 patients, 272 from the dental school and 107 from five private practices. A high percentage (95 percent) of both dental school and private patients felt they were adequately protected, while fewer than 2 percent expressed anxiety about infection control procedures being used in either setting. Factors such as gender, age, and years of formal education did not significantly affect attitudes toward infection control measures, but age and education were correlated with perceived knowledge of infectious diseases. Patients' reported knowledge of infectious disease had a significant effect on their decision to leave a practice if the dentist was HIV positive. A significantly higher percentage of dental school patients felt that barrier infection control techniques should be used routinely. Patients treated where such techniques were not routinely used nevertheless expressed satisfaction with that level of protection, implying that patients tend to accept the level of infection control being practiced where they receive treatment. PMID- 1744288 TI - Accreditation of predoctoral dental education: clinical outcomes assessment. AB - The Curriculum Outcomes Review and Evaluation (CORE) system of outcomes assessment used in the accreditation of Canadian Dental Faculties by the Commission on Dental Accreditation of the Canadian Dental Association is described. The CORE system, which has become an integral part of the regular accreditation site visit of Canadian dental predoctoral programs consists of (a) two methods of chart review, (b) assessment of the performance of a random sample of final year students in both diagnosis and treatment planning and in case presentation, (c) a structured observation in the clinical setting, (d) the application of a detailed and focused survey instrument prior to the site visit, and (e) the solicitation of feedback from involved students, faculty members, school administrators and accreditation site visitors. The overall response to the CORE program was favorable and plans to expand the program to dental hygiene accreditation are described. PMID- 1744289 TI - Use of screening blood studies in dental schools. PMID- 1744290 TI - Developing an undergraduate hospital dentistry program. PMID- 1744291 TI - Dental seniors' evaluation of their curriculum and the number of clock hours of instruction. PMID- 1744292 TI - Curriculum guidelines for predoctoral preventive dentistry. PMID- 1744293 TI - Curriculum guidelines for predoctoral implant dentistry. PMID- 1744294 TI - Extended selections for pyrethroid resistance in the German cockroach (Dictyoptera: Blattellidae). AB - Selection experiments with a pyrethrins-susceptible and a pyrethrins-resistant strain of German cockroaches, Blattella germanica (L.), were conducted for 17 generations with either permethrin or fenvalerate as the selecting agent. Large nymphs were left on treated glass surfaces for extended periods of time each generation. Mortality was assessed at 24 h. The level of resistance was determined periodically by time-mortality testing. The VPI-susceptible strain served as the basis for comparison. The pyrethrins-susceptible strain developed resistance to pyrethrins early in the selection process; this strain ultimately became resistant to allethrin, phenothrin, permethrin, fenvalerate, cyfluthrin, and cypermethrin. Fenvalerate caused faster development of resistance than did permethrin. The pyrethrins-resistant strain, selected with fenvalerate, quickly became resistant to allethrin, permethrin, phenothrin, and fenvalerate. Ultimately, it developed resistance to all nine pyrethroids tested. PMID- 1744295 TI - Effect of temperature on the toxicities of ten pyrethroids to German cockroach (Dictyoptera: Blattellidae). AB - Of 10 pyrethroids tested by topical application of male German cockroaches, Blattella germanica (L.), d-phenothrin was the least toxic at 19, 26, or 31 degrees C. lambda-cyhalothrin was most toxic. Pyrethroids with the alpha-cyano moiety (fluvalinate, fenvalerate, cypermethrin, esfenvalerate, tralomethrin, cyfluthrin, and lambda-cyhalothrin) were more toxic than those without this functional group (d-phenothrin, resmethrin, and permethrin). At LC50, toxicity was negatively related to temperature. Temperature-toxicity responses of five of seven alpha-cyano pyrethroids were parallel, possibly indicating qualitatively identical but quantitatively different levels of detoxification enzymes. PMID- 1744296 TI - Influence of attractants on behavior of screwworms (Diptera: Calliphoridae) in a tropical wet forest in Costa Rica. AB - In a mark-release-recapture study, sheep wounds and rotted liver were used as attractants to study movements of the screwworm fly, Cochliomyia hominivorax (Coquerel), in a Costa Rican tropical wet forest in the wet season. When sites were monitored for less than 1 h, liver attracted between 3 and 12.2 times more flies of both sexes than did wounds, but proportionately fewer gravid and parous females. Only 24.6% of females marked at liver sites were recaptured; seldom (3.1%) did they visit sheep wounds. Females originally marked at sheep wounds remained at the study site longer, visited both sheep and liver sites, and greater than 50% were recaptured. Some females were observed for 16 d and one laid four clutches of eggs. Only 8% of the marked males were recaptured and none was recaptured less than 2 d later. Only a small proportion of the adult screwworms at a locality visited wounds on sentinel sheep; the majority of the adults were transient. PMID- 1744297 TI - Alternative to sentinel animals for collecting egg masses from wild females of the screwworm (Diptera: Calliphoridae). AB - Egg masses from wild populations of the screwworm, Cochliomyia hominivorax (Coquerel), were obtained by collecting females from rotted liver, holding them for 3 d until egg maturation and then placing them on heated ground beef for oviposition. Nearly 50% of the females oviposited. Fertility of egg masses was 66 and 95% at the two collection sites. Decreased fertility was associated with collections of virgin females. Average weight +/- SD of the egg masses was 13.7 +/- 1.40 mg; the number of eggs per mass averaged 343. This method of obtaining egg masses from wild screwworm females is a cost-effective, sensitive alternative to the use of sentinel animals in the field. The use of rotted liver costs less, takes less time, and takes less equipment than the traditional sentinel animal technique. PMID- 1744298 TI - Influence of starvation and lighting on the movement behavior of the German cockroach (Blattodea: Blattellidae). AB - Computerized moving-image analysis measured the influence of starvation and lighting conditions on the locomotor activity of the German cockroach, Blattella germanica (L.). Starvation increased the distance traveled, velocity, and the proportion of time in motion of adult males and last instars but did not increase adult female movement. For females, males, and nymphs, starvation increased cockroach residence time around the source of water and harborage and decreased the distance traveled by females and nymphs around the observation arena's edge. Fluorescent light reduced the proportion of time in motion for males, but the velocity of males was greater in fluorescent light relative to infrared light. Adult males and females stopped more frequently in infrared light. Overall, males and nymphs were more mobile than females and they explored larger areas. The moving-image analysis technique is an efficient and accurate tool for observing movement of individual cockroaches and has applications in repellency, attractancy, and basic movement behavior studies. PMID- 1744299 TI - Seasonal movement and spatial distribution of the sheep ked (Diptera: Hippoboscidae) on Wyoming lambs. AB - When populations of adult sheep ked, Melophagus ovinus (L.), infesting unshorn lambs were monitored at the University of Wyoming Paradise Farm during 1986, we determined the body regions on which keds would be found at various times of the year and their seasonal population trends for optimal sampling. Results suggested that ked populations were consistently greater on the ribs than on any other area of the lamb. No significant differences were detected for ked populations between sides of a lamb. Distinct and similar ked population trends over time occurred only in the rib, thigh, shoulder, hind leg, belly, and hind flank areas of the lambs, suggesting that a significant seasonal migration did not occur. Analyses for seasonal population fluctuations indicated that ked populations increased in the winter and spring, decreased in summer and then increased again in the fall. Thus, sampling for keds in the rib area at shearing, which begins in March in Wyoming and runs through mid-April, would be an opportune time to detect keds. At other times of the year, the rib area should be inspected for presence of sheep ked. PMID- 1744300 TI - Advancing beyond pressure in ICU monitoring of the acute injured brain. PMID- 1744301 TI - Oxygen cost of breathing during weaning. PMID- 1744302 TI - Jugular bulb catheterization does not increase intracranial pressure. AB - Cerebral venous monitoring through jugular bulb catheterization (JBC) allows assessment of global oxygen delivery adequacy. Because of concern that venous obstruction by catheterization may cause or exacerbate intracranial hypertension, physicians are reluctant to puncture this vessel in brain-injured patients. We evaluated the impact of JBC on intracranial pressure (ICP). 37 consecutive pediatric patients with jugular bulb catheters and ICP monitoring were studied. ICP was monitored in 28 patients during JBC. Also immediately after JBC and daily thereafter the contralateral, ipsilateral, and bilateral jugular veins were compressed in all 37 patients to assess patency of these vessels. Change in ICP was noted. If ICP increased more than 5 torr, compression was stopped. Preinsertion ICP was 17.3 +/- 5.1 and postinsertion 17.2 +/- 5.1 torr. The maximum rise in ICP was 2 torr in a single patient while 6 others had a decrease in ICP. 120 compression tests were performed. Compression ipsilateral to the catheter caused the ICP to rise from 16.0 +/- 4.3 to 18.4 +/- 4.4 torr, and in contralateral compression 15.9 +/- 4.2 to 17.0 +/- 4.4. Neither the duration of catheterization nor the precompression ICP correlated with the rise in ICP. These data revealed no evidence of jugular venous obstruction in the catheterized vessel. We conclude that JBC can be performed in patients without aggravating an elevated ICP. PMID- 1744303 TI - Plasma catecholamines and oxygen consumption during weaning from mechanical ventilation. AB - Previous studies on oxygen consumption (VO2) during weaning from mechanical ventilation assumed that an increase in VO2 (delta VO2) reflected oxygen consumption by respiratory muscles (VO2RESP), and proposed delta VO2 as a weaning predictor. We measured VO2 CO2 production (VCO2) and plasma catecholamines in 20 short-term ventilated patients during weaning by SIMV and CPAP. delta VO2 as a percentage of VO2 during spontaneous ventilation (delta VO2%) ranged from 4.8% to 41.5%. VCO2 also increased and correlated with VO2. Plasma adrenaline and noradrenaline increased significantly to levels known to produce considerable increases in metabolic rate. Mean arterial pressure and heart rate concomitantly increased, but spontaneous minute ventilation decreased. Thus, since the increased plasma catecholamines are calorigenic, the assumption that delta VO2 represents VO2RESP is incorrect. Although mean delta VO2% of successfully weaned patients was significantly less than that of failure-to-wean patients, the wide scatter of individual values in the latter group excludes delta VO2% as an accurate weaning predictor. PMID- 1744304 TI - The cost of an intensive care unit: a prospective study. AB - The cost of intensive care for patients admitted to the ICU were estimated. Patients suffering from severe combined acute respiratory and renal failure who required mechanical ventilation and renal replacement therapy (SCARRF-D) cost per day significantly more than non-renal patients (pounds 938 compared to pounds 653 per patient respectively) and their average length of stay in hospital is nearly 4 times as long (28.8 compared to 7.6 days respectively). Approximately 44% of the total cost was staff related (28% for the provision of nurses and 16% for the rest). Retrieving information related to cost was difficult, time consuming and labour intensive. PMID- 1744305 TI - Combined high-frequency ventilation in children with severe adult respiratory distress syndrome. AB - Six children conventionally ventilated for acute pulmonary parenchymal failure developed severe hypoxemia (mean PaO2 48 +/- 7 mmHg at an FiO2 of 0.95 +/- 0.08) persisting for more than 6 h despite a progressive increase in positive end expiratory pressure (PEEP) to 14.7 +/- 1.5 cmH2O. Combined high-frequency jet ventilation (HFJV, mean rate 225 b/min superimposed on small tidal volume conventional ventilation) resulted in a sustained increase in PaO2 to 93 +/- 21 mmHg, p less than 0.05 while peak inspiratory pressure decreased from 47 +/- 8 to 35 +/- 6 cmH2O and positive end expiratory pressure could be reduced to 5.8 +/- 4.5 cmH2O, p less than 0.05 and FiO2 to 0.88 +/- 0.10. This improvement occurred without new barotrauma nor deleterious effects on hemodynamic function or diuresis. After a mean of 62 h of combined function or diuresis. After a mean of 62 h of combined HFJV, persistent improvement in gas exchange allowed us to resume conventional mechanical ventilation at lower airway pressures in 4 children who continued to improve and survived. The 2 other children maintained satisfactory gas exchange on combined HFJV, but ultimately died from multiple organ failure. We conclude that combined HFJV might prove helpful to relieve profound hypoxemia and possibly decrease the risk of barotrauma in children with catastrophic pulmonary failure. PMID- 1744306 TI - Antibiotic levels in bronchial tree and in serum during selective digestive decontamination. AB - Selective digestive decontamination has been found to prevent pulmonary infections in mechanically ventilated patients. The aims of this study were: 1) to determine whether detectable levels of antibiotics could be found in bronchial tree secretions of patients receiving SDD, and 2) to evaluate antibiotic serum levels. In 15 patients receiving mechanical ventilation and SDD for 10 days or more, tobramycin and amphotericin B levels were determined every 3 days in the following specimens: tracheal aspirates, distal bronchial secretions and blood samples. 82% of tracheal aspirates contained detectable (greater than 0.18 mg/l), tobramycin concentrations; the levels varied widely between patients and large day-to-day variations were observed. Every patient had at least 1 tracheal aspirate with tobramycin level higher than 0.5 mg/l during his course. 40% of distal specimens contained detectable tobramycin levels (10 patients). Serum determinations showed detectable concentration of tobramycin in 50% of the specimens (9 patients). Two patients with renal failure had serum tobramycin levels higher than 2 mg/l. In 13 tracheal aspirates cultures were positive and 15 species were isolated; 13 had a MIC higher than the corresponding tobramycin level in tracheal secretions. We conclude that substantial levels of antibiotics can be found frequently in respiratory tract specimens of patients receiving SDD. Therefore, the usual microbiological criteria used to assess respiratory tract infection may be unreliable in this setting and other criteria may be required. Follow-up of antibiotic serum levels is required, especially in patients with renal failure. PMID- 1744307 TI - Injurious sleep behavior disorders (parasomnias) affecting patients on intensive care units. AB - There are no previous reports on parasomnias (sleep behavior disorders) affecting patients on intensive care units (ICUs). During 8 years of clinical practice, we evaluated over 200 adults with complaints of injurious, sleep-related behaviors, 20 of whom had ICU admissions while their parasomnias had been active and generally undiagnosed/untreated. Mean age during ICU confinement was 62.8 (+/- SD 13.1) years; 85.0% (17/20) were males. Patients underwent comprehensive clinical examinations along with extensive polysomnographic and audiovisual monitoring (electrooculogram, 9 channel EEG with paper speeds of 15 and 30 mm/sec, electromyogram [submental and 4 limbs], EKG, airflow). The polysomnographic studies were diagnostic for the REM sleep behavior disorder (vigorous dream enactment during rapid eye movement [REM] sleep) in 85.0% (17/20) of patients, and for night terrors/sleepwalking in 15.0% (3/20). Three groups of parasomnia ICU relationships were identified: i) Parasomnias originating in ICUs, stroke induced (n = 3); ii) Admission to ICUs resulting from parasomnia-induced injuries: C2 odontoid process fracture and C3 spinous process fracture with severe concussion (n = 2); iii) Parasomnias in patients admitted to ICUs for various other medical problems (n = 15). Physicians should be thus alerted about the possibility of injurious, but usually treatable, parasomnias in ICU patients. PMID- 1744308 TI - An experimental study of different ventilatory modes in piglets in severe respiratory distress induced by surfactant depletion. AB - In 19 anesthetized piglets 3 ventilatory modes were studied after inducing pulmonary insufficiency by bronchoalveolar lavage by the method of Lachmann. The lavage model was considered suitable for reproduction of severe respiratory distress. This model was reproducible and stable with respect to alveolar collapse, decrease in static chest-lung compliance and increase in extravascular lung water. The ventilatory modes studied were volume-controlled intermittent positive-pressure ventilation (IPPV), pressure-controlled inverse ratio ventilation (IRV), and pressure-controlled high-frequency positive-pressure ventilation (HFPPV). The 3 ventilatory modes were used in random sequence for at least 30 min to produce a ventilatory steady state. Ventilation with no PEEP, permitting alveolar collapse, was interposed between each experimental mode. The ability to open collapsed alveoli, i.e. alveolar recruitment, was different. The recruitment rate for IPPV was 74%, but for IRV and HFPPV it was 95%, respectively. Although IRV provided the best PaO2, this was at the expense of high airway pressures with circulatory interference and reduced oxygen transport. In contrast to this, HFPPV provided lower airway pressures, less circulatory interference and improved oxygen transport. In the clinical setting there might be negative effects on vital organs and functions unless the ventilatory modes are continuously and cautiously adapted to the individual requirements in different phases of severe respiratory distress. Therefore, one ventilatory strategy could be to "open the airways" with IRV, but then switch to HFPPV in an attempt to maintain the airways open with lesser risk of barotrauma and with improved oxygen transport. PMID- 1744309 TI - Acute trichloroethylene poisoning by ingestion: clinical and pharmacokinetic aspects. AB - Five hours after ingestion of an unknown amount of trichloroethylene (TCE) a 32 year-old woman was admitted to hospital in deep coma. The neurological condition remained unchanged for 3 days, after which there was an improvement of the central nervous system function. The concentrations of TCE in the blood, which were measured during 7 days after the solvent ingestion, gave us the opportunity to study some toxicokinetic parameters of TCE. Using a physiologically based pharmacokinetic model, the toxicokinetic parameters and blood concentrations of TCE are discussed in relation to the neurological conditions. Moreover the same model has suggested that the alveolar hyperventilation during the first 12 h following the TCE poisoning is the only treatment which may shorten the duration of the poisoning. PMID- 1744310 TI - Pancreatitis related to severe acute hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis. AB - We report a clinical observation of acute pancreatitis due to severe hypertriglyceridemia in a pregnant woman. In order to decrease the serum triglyceride level rapidly, two lipaphereses were undertaken using the double filtration technique. This lipoprotein apheresis technique is briefly described and the efficacy in reducing rapidly hypertriglyceridemia is outlined. Like in 3 previously published reports, the patient had a rapid recovery, confirming that lipoprotein apheresis should be an adequate and a well-tolerated treatment in such a condition. PMID- 1744311 TI - Heparin-induced thrombocytopaenia complicated by bilateral adrenal haemorrhage. AB - Acute adrenal insufficiency due to bilateral adrenal haemorrhage is an important clinical diagnosis and its association with heparin-induced thrombocytopaenia is infrequent. We report on a patient in whom life threatening acute adrenal insufficiency occurred consequent to such an association. The clinical manifestations simulated septic shock, highlighting the need to consider specifically acute adrenal insufficiency in such settings, and institute therapy promptly prior to obtaining results of confirmatory tests. PMID- 1744312 TI - Continuous arterio-venous haemodialysis during emergency hepatic retransplantation. PMID- 1744313 TI - Recovery from adult respiratory distress syndrome after high dose corticosteroids. PMID- 1744314 TI - Vasopressin in septic shock--a useful or dangerous agent? PMID- 1744315 TI - Euthanasia. PMID- 1744316 TI - Fortuitous discovery of the association of true and false left ventricular aneurysm in a patient in cardiogenic shock. PMID- 1744317 TI - Severe theophylline toxicity treated with oral activated charcoal. PMID- 1744318 TI - TNF levels in severe malaria treated by exchange transfusion. PMID- 1744319 TI - Acute renal failure in paediatric patients: the role of continuous haemofiltration. PMID- 1744320 TI - In search of the dysoxic threshold. PMID- 1744321 TI - Five years experience with continuous extracorporeal renal support in paediatric intensive care. AB - Continuous arterio-venous haemofiltration (CAVH) and continuous veno-venous haemofiltration (CVVH) were used as renal support in 52 critically ill infants and children with acute renal failure. The majority of the patients were on mechanical ventilation (90%) and needed vasopressor support (85%). Uraemia was satisfactorily controlled with both treatment modes. Post-treatment serum urea levels were not different between survivors (94 +/- 8.8 mg/dl) and non-survivors (99.5 +/- 8.8 mg/dl). There were significant differences between survivors and non-survivors in the mean arterial pressure (64.7 +/- 3.8 vs 48.0 +/- 2.2 mmHg, p less than 0.001), the number of organ system failures (2.9 +/- 0.16 vs 3.8 +/- 0.21, p less than 0.025), and the severity of illness assessed by the acute physiologic score for children (APSC 19.4 +/- 1.9 vs 26.3 +/- 1.9, p less than 0.01). The overall mortality was 48%. The mortality in the CVVH group (65%) was higher than in the CAVH group (40%). Death was significantly related to sepsis (p less than 0.005) and multiple system organ failure (p less than 0.005). A major complication during CAVH was one femoral artery thrombosis after 12 days of treatment. Technical problems were only observed during CVVH. CAVH and CVVH are safe and effective methods of continuous renal support for critically ill paediatric patients with multiple system organ failure. CAVH is simpler, needs no specially trained staff and seems to the ideal renal replacement system for critically ill infants. PMID- 1744322 TI - Delivery dependent oxygen consumption in patients with septic shock: daily variations, relationship with outcome and the sick-euthyroid syndrome. AB - Delivery dependent oxygen consumption (DDOC) is observed in patients with sepsis and vital organ dysfunction, and has been related to outcome. Similarly the sick euthyroid syndrome is associated with a high mortality. We examined the daily variations of DDOC and its relation to hormonal changes, particularly those of the thyroid. In 22 patients, 14 with septic shock and 8 post-operative controls, oxygen delivery was increased by increasing cardiac output with vasodilation by phentolamine, during a total of 207 days. DDOC varied markedly between consecutive days in individual patients with sepsis, in both survivors and non survivors. DDOC was related to severity of illness, assessed by APACHE II score (r = 0.50, p = 0.017), and plasma levels of triiodothyronine (T3), r = -0.49, p = 0.011, and thyroxine (T4), r = -0.53, p = 0.012. No correlation was observed between DDOC and outcome, nor blood levels of lactate, epinephrine, norepinephrine, dopamine or cortisol. In conclusion, we observed a marked disturbance of systemic oxygen uptake autoregulation in patients with septic shock which varied during the clinical course and was related to the sick euthyroid syndrome. PMID- 1744323 TI - Is minitracheotomy a simple and safe procedure? A prospective investigation in the intensive care unit. AB - Patients with imminent respiratory failure due to sputum retention were assessed for minitracheotomy (MT). MT was considered potentially useful in 79 patients but only attempted in 73, 54 men and 19 women, aged 23-81 years (median 65 years). Insertion of the cannula failed in 4 cases. Sputum retention and atelectasis were successfully treated in 87% (N = 60). Treatment by MT in medical and neurological patients seems as effective as in surgical patients (success rate 81% versus 90%). The frequency of complications was 16%. Most complications were insignificant and occurred during cannulation, but a few severe complications were seen. To minimize the number of these it is essential that MT is done only by doctors who are familiar with the procedure. MT can be recommended for treatment of sputum retention and atelectasis in surgical and medical/neurological intensive care patients with preserved cough function. PMID- 1744324 TI - Usefulness of severity indices in intensive care medicine as a predictor of nosocomial infection risk. AB - To evaluate the relationship between severity and nosocomial infection in critical patients, we have conducted a prospective study at the Intensive Care Unit of the University of Granada Hospital (Spain). Patients' severity was evaluated by APACHE II and TISS. We found a positive association with nosocomial infection risk for an APACHE II score greater than 12 points (RR = 2.45) and for first-day TISS greater than 20 points (RR = 2.51). With a multivariate analysis we did not find an association between APACHE II and nosocomial infection risk, but each TISS point suggests an infection risk increment of 6%. We concluded TISS may be considered a good infection risk predictor. TISS could also be taken into account when nosocomial infection rates from several ICUs are compared. PMID- 1744325 TI - Time oriented score system (TOSS): a method for direct and quantitative assessment of nursing workload for ICU patients. Italian Multicenter Group of ICU research (GIRTI). AB - A method for direct quantitation of nurses' workload required by ICU patients is described. Each nursing activity has been timed in 14 different ICUs participating in the multicentre study, and the results averaged. Nursing acts were grouped in different homology lists, complied according to operative similarities. Some lists include general nursing acts, which are common to all patients admitted to ICU, others include acts peculiar to different organ system abnormalities or acts ancillary to the general group, finally one list includes emergency or occasional acts which are not encountered in every patient. The TOSS is a simple and rapid method for ICU nurses' workload assessment, can be computed both at admission and during the stay in ICU, and can provide factual information on the nurse/patient ratio necessary in a specific environment. TOSS validation was conducted with a yearly prospective study collecting 2710 patients. TOSS values varied according to diagnosis, severity of illness (SAPS) and intensity of processes (TISS), and TOSS specificity was demonstrated by the possibility of selecting a wide combination of nurse/patient ratios from 1:4 to 1:1 not possible with TISS. PMID- 1744326 TI - The haemodynamic effects of intermittent haemofiltration in critically ill patients. AB - The haemodynamic effects of intermittent high volume venovenous haemofiltration were studied in 13 critically ill patients. The mean negative fluid balance during filtration was 1.21 and the mean duration of treatment 3 h 40 min. The cardiac index fell initially (4.5 +/- 0.2 to 3.8 +/- 0.21/min/m2; p less than 0.05) but then remained stable throughout treatment before returning to baseline at the end of haemofiltration. The mean arterial pressure was unchanged with an increase in the systemic vascular resistance (651 +/- 33 to 765 +/- 65 dyne.s/cm5; p less than 0.05) suggesting that vascular responsiveness is maintained during haemofiltration. PMID- 1744327 TI - Subclavian vein catheterization in critically ill children: analysis of 322 cannulations. AB - Complications in 322 percutaneous subclavian vein catheters placed in 272 children by the infraclavicular approach were investigated prospectively. Ages ranged from 4 days to 15 years. Incidents during catheter introduction occurred in 13 cases, and were more common when insertion was on the right side (p less than 0.01). Nine (2.8%) required urgent treatment: (6 pneumothorax, 1 hydrothorax, and 2 hemothorax). Anomalous lodging of the catheter tip was more common when insertion was on the right side (p less than 0.05). Complications during catheter maintenance were 3 venous thromboses, 3 catheter obstructions, and 7 migrations out of position. There was no significant difference in complications related to age. Catheter cultures were positive in 33 (17%) of 190 catheters cultured (27 through colonization and 6 through catheter-related sepsis). Staph. epidermidis was the organism most frequently isolated (19 cases; 58%). Catheterization time of more than 5 days and catheter-related sepsis were statistically associated (p less than 0.05). Staph. epidermidis isolation and duration of cannula use were statistically related (p less than 0.01). No catheter-related deaths occurred. We conclude that subclavian vein catheterization is a simple and useful procedure that entails relatively few serious complications when performed by experienced pediatricians. PMID- 1744328 TI - The P50 is reduced in critically ill patients. AB - A prospective study was designed to measure the P50 in 20 critically ill patients, and compare it with the P50 measured in 20 normal individuals. Arterial blood gases, lactate, haemoglobin (Hb) and phosphate (PO4) levels were also measured and compared with the P50 in the critically ill patients. The mean P50 of the critically ill patients was 24.5 mmHg (SD +/- 2.9) and was significantly lower than the mean P50 of 26.2 (SD +/- 2.2) in the normal individuals (p less than 0.05). In the critically ill patients, strong correlations were observed between the P50 and the arterial pH and base excess (BE) levels, with coefficients of 0.79 and 0.69 respectively whereas correlations between the P50 and arterial oxygen tension (PO2), carbon dioxide tension (PCO2), lactate, Hb and PO4 levels were poor, with correlations of 0.001, 0.008, 0.07, 0.13 respectively. It is concluded that the P50 is commonly reduced in critically ill patients, and has a strong correlation with arterial pH and BE. PMID- 1744329 TI - Preliminary clinical trials of a computer-based cardiac arrest alarm. AB - The use of a high reliability cardiac arrest alarm utilising the continuously monitored values of patient heart rate and mean arterial blood pressure is described, based on a sample of 167 patients monitored for a total of 5116 h. The analogue heart rate and mean blood pressure signals are sampled at 1 s intervals, and a smoothing algorithm is applied to each of the resulting series which rejects artefacts, and identifies slope and step changes in each. Certain combinations of events in the 2 series, occurring within a preset time window, determine whether a cardiac arrest alarm or warning signal should be activated by the system. A total of 30 acute events occurring in 14 patients during the course of the study were each identified within 10 s. No cardiac arrest event was misdiagnosed by the algorithm during the period of the study. The algorithm also generates warnings which may have predictive value, and which will be the subject of further research. A final false alarm rate of about 1/200 h of monitoring was observed in adults (1/50 h in children), with evidence that these rates could be substantially improved. PMID- 1744330 TI - Respiratory changes after open-heart surgery. AB - Breathing pattern was studied non-invasively in 20 coronary artery bypass surgery patients before the operation and post-operatively after weaning from mechanical ventilation. Post-operatively minute ventilation (VE), breathing frequency (Fr) and mean inspiratory flow (VT/TI) increased (28%, 42%, 27%; p less than 0.01, p less than 0.001, p less than 0.01, respectively), while tidal volume (VT) decreased (15%, p less than 0.025). CO2 production (VCO2) and oxygen consumption (VO2) increased postoperatively (p less than 0.001 for both), contributing to the increase in ventilatory demand. Reduced variation of VT and Fr (p less than 0.001, p less than 0.01, respectively) and number of sighs (p less than 0.001) were characteristic of the post-operative breathing pattern. Post-operatively an increase in the contribution of rib cage (%RC) to tidal volume in the supine position was observed suggesting reduced motion of the diaphragm. All patients had atelectasis, 17 had pleural fluid and only 6 normal vascularity post operatively. The shallow breathing in combination with increased ventilatory demand, impaired gas exchange and the surgical trauma of the thorax predispose to postoperative respiratory complications. PMID- 1744331 TI - Upper airway obstruction due to erysipelas. AB - Erysipelas is a rare cause of airway compromise. A case of a 57-year-old female is described who developed upper airway obstruction secondary to erysipelas of the neck. Emergency treatment by awake fiberoptic bronchoscopy with intubation over the bronchoscope followed by intravenous antibiotics produced rapid clinical improvement. Lymphatic obstruction of the laryngeal structures is the most likely physiologic mechanism. PMID- 1744332 TI - ARDS--associated with adult Still's disease. PMID- 1744333 TI - Septic shock and multiple organ failure: treatment with haemofiltration? PMID- 1744334 TI - Using the health belief model for bulimia prevention. AB - The author discusses application of the Health Belief Model to bulimia prevention (reduction of bulimic-like behaviors of food obsessions, bingeing, and various forms of purging). She considers the individual's beliefs about bulimia and bulimic-like behaviors as a means of predicting the likelihood of behavior change to prevent clinically diagnosable bulimia, includes a description of each Health Belief Model component, and offers implications for further research. PMID- 1744335 TI - HIV-related sexual behaviors of college students. AB - A follow-up study explored the prevalence of behavioral risk factors for HIV infection in a population of college students. Two hundred forty-three single students ranging in age from 17 to 24 years who identified themselves as heterosexual completed questionnaires related to planned and unplanned sexual intercourse and such other factors as alcohol and nonprescription drug use that might increase the risk of HIV infection. Forty-seven percent of the men and 57% of the women stated that they had had sexual intercourse from 1 to 5 times primarily because they were intoxicated, a phenomenon that increased with age until only 19% of those over 21 had never had sex because of intoxication. Seventeen percent of the sexually active men and 21% of the women said that they had used condoms. Nineteen percent of the men and 33% of the women acknowledged consenting to sexual intercourse because they felt awkward in refusing. The dangerous interaction between alcohol use and high-risk sexual activities suggested that college HIV prevention efforts should make the connection between the two risk factors explicit. PMID- 1744336 TI - The periodic health examination in college students revisited. AB - The periodic health examination is a group of tasks carried out by physicians and nurses at regular intervals, but not always yearly, to determine either the risk of subsequent disease or to identify disease in its early, asymptomatic state. The Guide to Clinical Preventive Services, published in 1989 by the United States Preventive Services Task Force, sets common American standards for these procedures. The guide lists those preventive activities recommended for persons aged 19-39 years. Every patient encounter in our student health services should be considered an opportunity for preventive activities. This article offers a simple check list for office use. PMID- 1744337 TI - College health services in California. AB - College health services are an underrecognized segment of California's health delivery system. Higher education institutions in California vary in their arrangements for the provision of health services. Some of the smaller institutions provide nurse triage, first aid, and referral only, whereas other institutions provide 24-hour-per-day/7-day-per-week comprehensive ambulatory and inpatient services. More than 200 full-time equivalent physicians are employed in college health services in California. Patient profiles served by college health services targeted the traditional college student age range. Some institutions, however, have expanded their services to include nonstudent university employees and their dependents. Comparing numbers of outpatient visits and professional staffing requirements to student enrollment showed significant variability between institutions, depending upon the scope of services provided (basic, intermediate, comprehensive) and the type of student population (residential, commuter, mixed). PMID- 1744338 TI - Nursing diagnosis as a needs assessment tool for campus health promotion. PMID- 1744339 TI - Implementing a comprehensive health education program for international students. PMID- 1744340 TI - The need for an expanded college consumer health curriculum. PMID- 1744341 TI - Baby boom parents and homosexuality: continued challenge for college health educators. PMID- 1744342 TI - Ethics and dental amalgam removal. PMID- 1744343 TI - The final curtain? PMID- 1744344 TI - The future of fluoride. Correction. PMID- 1744345 TI - Dental associations, FDA question safety of lasers on hard tissues. PMID- 1744346 TI - Regenerating the periodontium in advanced periodontal disease. AB - Current techniques can benefit patients with advanced periodontal disease and oral injuries. Future technology offers even greater promise for regenerating periodontal tissue. PMID- 1744347 TI - Using endosseous dental implants for patients with ectodermal dysplasia. AB - Congenitally missing teeth and poorly developed or absent alveolar ridges are signs often associated with various types of ectodermal dysplasia. Endosseous dental implants may be used to support fixed mandibular prostheses in patients with ectodermal dysplasia. Anatomical factors and age considerations require careful attention to treatment planning. PMID- 1744348 TI - The enemy is us. Some thoughts on the shortage. PMID- 1744349 TI - Managing occlusal surfaces of young permanent molars. AB - The practice of restoring occlusal surfaces of young permanent teeth with just amalgam or waiting and watching for caries to occur is outdated. Today, there are several treatment options. PMID- 1744350 TI - Capitation: the choice is yours. PMID- 1744351 TI - HIV testing. PMID- 1744352 TI - Opportunity knocks in market for allied dental personnel. PMID- 1744353 TI - Mediator release in aspirin-induced reactions. PMID- 1744354 TI - Near-fatal asthma: clinical and physiologic features, perception of bronchoconstriction, and psychologic profile. AB - We studied 19 subjects with asthma (11 men and eight women, aged 20 to 66 years), 6 months to 5 years after a near-fatal (NF) episode of asthma (NF group). Mean duration of asthma was 16.3 +/- 2.4 years. On reevaluation, all subjects were using an inhaled beta 2-agonist and inhaled steroids (mean daily dose of budesonide, 1070 micrograms [N = 5], and beclomethasone, 1079 micrograms [N = 14]). Two subjects were taking prednisone, 10 and 15 mg/day. Subjects were matched for age, sex, atopic status, baseline FEV1, and medication use to a control group (C group) of subjects with asthma who had never experienced an NF asthma episode. All subjects had the following evaluation: (1) questionnaire on the characteristics of their asthma, (2) spirometry, (3) morning and evening measurements of peak expiratory flow rates (PEFR) with daily recordings of asthma symptoms for 4 weeks, and (4) psychometric evaluation with the Minnesota Multiphasic Personality Inventory. Ten subjects of the NF group and 13 of the C group had a methacholine challenge with scoring of dyspnea on a modified Borg scale. Mean percent predicted (+/- SEM), FEV1, FVC, and PEFR were similar for the NF and C groups with respective values of 63.4 (4.4), 61.3 (5.6), 81.1 (4.5), 79.1 (3.8), 61.3 (5.6), and 62.4 (6.1). Geometric mean of the provocative concentration of methacholine causing a 20% drop in FEV1 (milligrams per milliliter) was 0.61 for the NF group (N = 10) and 1.18 for the C group (N = 13).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744355 TI - Assay for the major dog allergen, Can f I: investigation of house dust samples and commercial dog extracts. AB - Monospecific rabbit antibodies were used to develop a sensitive two-site enzyme immunoassay to measure a major dog hair and dander allergen, Can f I. This Can f I assay demonstrated no reaction with 17 heterologous allergen sources, including dog albumin, cat, guinea pig, and horse. Analysis of serial dilutions of purified Can f I and the international standard for dog was parallel. The assay was considered specific for Can f I with a lower limit of detection at 0.03 micrograms/ml. Total imprecision was from 2% to 6%. Commercial dog extracts for specific immunotherapy contained from 0.7 to 290 micrograms of Can f I per milliliter. The assay was used to measure Can f I in 136 house dust samples collected from 103 homes across the United States. Concentration of the dog allergen was expressed as micrograms of Can f I per gram of dust. Prevalence of Can f I in the dust samples ranged from less than 0.3 to 10,000 micrograms/gm. Serial dilutions of samples containing Can f I were parallel to the standard. The median Can f I value for homes with a dog in residence was 120 micrograms/gm, and for homes with no dog, 3 micrograms/gm. With few exceptions, homes with no dog in residence had less than 10 micrograms/gm. This Can f I assay will provide useful information for assessing commercial extracts as well as monitoring dog-allergen exposure and allergen-control methods. PMID- 1744356 TI - Asthmatic responses to passive cigarette smoke: persistence of reactivity and effect of medications. AB - The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined "reactors" and nine "nonreactors" to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five/six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV1 on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown. PMID- 1744357 TI - Findings before diagnoses of asthma among the elderly in a longitudinal study of a general population sample. AB - Forty elderly subjects who denied ever having asthma or emphysema on enrollment in a longitudinal epidemiologic study later reported consulting a doctor for asthma when they were older than 60 years of age. The average age at which the diagnosis was reported was 70.8 years, after a mean follow-up of 8.5 years. Findings on enrollment in the newly diagnosed subjects with asthma are compared with findings in the 1145 subjects who provided follow-up information when they were older than age 60 years but had never developed asthma. At the time of enrollment, most subjects later diagnosed as having asthma already had wheezing symptoms, suggesting at least a mild asthmatic state, and many subjects had impaired ventilatory function, a positive allergy skin test (especially in association with rhinitis), and blood eosinophilia. Thirty-five percent of the subjects recalled "respiratory trouble before age 16" despite denying prior asthma. The likelihood of a new asthma label was very closely related to the age sex-standardized serum-IgE level before diagnosis. Newly diagnosed subjects with asthma demonstrated much greater rates of decline in FEV1 than control subjects or than subjects who already had known asthma on enrollment. We conclude that (1) symptoms suggesting asthma are usually present for many years before the diagnosis of the disease in elderly subjects, (2) the serum-IgE level is closely related to the likelihood of a subsequent asthma diagnosis, even in this age group, and (3) a rapid fall in lung function often occurs around the time of initial diagnosis. PMID- 1744358 TI - The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure. AB - Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT treated group. Also, the EOS cationic protein levels were raised in the non-IT treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment. PMID- 1744359 TI - Recombinant allergens for immunoblot diagnosis of tree-pollen allergy. AB - Diagnosis of type I allergy essentially depends on the availability of defined allergens, which can be provided by recombinant deoxyribonucleic acid (DNA) technology. We have previously isolated the c(complementary)DNAs encoding the major birch-pollen allergen, Bet v I, and another allergen with a molecular weight of 14 kd that was identified as birch profilin and designated Bet v II. These cDNAs were isolated from a lambda gt11 expression library by screening with the serum IgE from allergic patients. To obtain expression in Escherichia coli of recombinant allergens without additional fused polypeptides, both cDNAs were inserted into the plasmid pKK223-3. E. coli cells expressing Bet v I and birch profilin (Bet v II) were used for the preparation of recombinant proteins. These proteins were tested for their IgE-binding properties on immunoblots with sera from 100 different birch pollen-allergic patients. All patients' sera, which reacted with the natural allergens, Bet v I and Bet v II, demonstrated an identical IgE-binding pattern to recombinant birch-pollen allergens. Recombinant allergens may therefore be useful for the setup of diagnostic tests that allow the discrimination of different IgE-binding patterns as well as for patient tailored immunotherapy. PMID- 1744360 TI - Cockroach allergenic activity: analysis of commercial cockroach and dust extracts. AB - Previous investigations demonstrated that cockroach whole bodies and feces are important sources of allergens in the induction/exacerbation of bronchial asthma. The current study investigated different cockroach source materials, commercial extracts, and house dust extracts for cockroach allergenic activity. In general, extracts from four different sources of either American or German cockroaches contained similar amounts of allergenic activity by RAST inhibition. Three commercial American cockroach extracts compared by RAST inhibition had similar allergenic activity on an equal protein basis. Skin test results correlated house dust reactivity to both commercial and inhouse cockroach wholebody extracts and to fecal extracts. Six different samples of house dust obtained from vacuum cleaners in the New Orleans area and three commercially obtained house dust extracts contained varying quantities of cockroach allergenic activity by RAST inhibition. These studies demonstrate that commercial cockroach extracts vary in allergenic activity and that all house dust extracts tested contain cockroach allergens. PMID- 1744361 TI - The 31 kd major allergen, Alt a I1563, of Alternaria alternata. AB - A component of Alternaria extract, previously identified as the major allergen, Alt a I1563, was purified to homogeneity from Alternaria mycelium by means of acetone precipitation and ion-exchange chromatography. The homogeneity of Alt a I1563 was assessed by one single band after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by one single radiolabeled band after transfer to nitrocellulose, and by one single peak after size-exclusion chromatography by high-performance liquid chromatography. Alt a I1563 was isolated as a heat-stable acidic glycoprotein (carbohydrate content, 20%; pI, 4.0 to 4.5; 31 kd). The role of the carbohydrate moiety in the allergenicity is suggested. This major allergen is located in the cytoplasm of mycelium and spore. PMID- 1744362 TI - Acute consumption of C1 inhibitor in a patient with acquired C1-inhibitor deficiency syndrome. AB - Acquired C1-inhibitor (C1 INH) deficiency is usually found in association with an underlying disease that is believed to be responsible for increased C1 INH catabolism, ultimately leading to the development of C1 INH deficiency. We report a remarkable patient with acquired C1 INH deficiency in whom a unique progression of complement- and contact-system abnormalities has been observed. S. G. suffers from recurrent episodes of angioedema and hypotension. Results of repeated complement studies were initially normal, and the patient was diagnosed as having idiopathic anaphylaxis. Two years later, the patient was found to develop acute consumption of C1 INH with activation of the complement and contact systems during episodes of angioedema. The patient continued to have normal C1 INH levels and to have no evidence for complement- or contact-system activation between attacks of angioedema. One year later, her course evolved into a more typical course for acquired C1 INH deficiency consisting of continuously low functional C1 INH levels with evidence of activation of the complement and contact systems. S. G. provides a unique insight into the development of acquired C1 INH deficiency. PMID- 1744363 TI - Airborne dust mite allergens: comparison of group II allergens with group I mite allergen and cat-allergen Fel d I. AB - The form in which allergens become airborne is important because it may influence both symptoms caused by allergen exposure and methods used to reduce exposure. The group I allergens from dust mites only become airborne during disturbance and fall rapidly, which is in keeping with their being carried on fecal pellets. Their mean size is approximately 20 microns in diameter. By contrast, the cat allergen Fel d I is airborne on particles varying from greater than 10 to less than 2 microns in diameter, some of which remain airborne even without disturbance. A second group of mite allergens, molecular weight 14,000, are equally important and are associated predominantly with mite bodies. With a monoclonal antibody-based assay and a cascade impactor, we have investigated the form in which group II mite allergens become airborne. The results reveal that these allergens only become airborne during disturbance and that they fall within 15 minutes. However, the mean size of particles carrying group II allergens appears to be slightly smaller than the mean size of particles carrying group I allergens. In addition, the quantities of group II allergen becoming airborne during disturbance (mean, 26 ng/m3) could not be explained by the quantity found in fecal particles. Thus, group II mite allergens become airborne in a form quite distinct from cat allergens and very similar to group I mite allergens; however, it appears unlikely that fecal particles are the main form in which group II allergens become airborne. PMID- 1744364 TI - Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. AB - Activated T-lymphocytes may regulate the eosinophilic inflammation of bronchial asthma. In the present study, we investigated T cell activation and eosinophilia in blood and bronchoalveolar lavage (BAL) in 17 patients with asthma not receiving steroid treatment. Compared to normal individuals, BAL from patients with asthma contained significantly increased numbers of both lymphocytes and eosinophils (EOSs). The lymphocytosis consisted of increased numbers of both CD4+ and CD8+ T cells, and these T cell populations expressed elevated levels of T cell activation markers (interleukin-2 receptor [CD25], HLA-DR, and very late activation antigen 1). Close correlation was found between numbers of BAL CD4+ IL 2R+ T cells and numbers of EOSs. Moreover, the numbers of activated T cells and EOSs were related to the severity of asthma as measured by impairment of FEV1 and increased methacholine bronchial responsiveness. We demonstrate in both blood and BAL a close correlation between T cell activation, eosinophilia, and severity of asthma, suggesting that recruitment and activation of lymphocytes and EOSs are fundamental to the pathogenesis of bronchial asthma. PMID- 1744365 TI - Sensitization to Blomia tropicalis and Lepidoglyphus destructor in Dermatophagoides spp-allergic individuals. AB - Serum was collected from 77 atopic subjects from Cartagena, Colombia, who had a positive skin test (greater than or equal to 3 mm) to either Dermatophagoides farinae (Df) (73) or D. pteronyssinus (Dp) (70). Twenty-nine healthy volunteers with negative allergy histories and negative skin tests were used as control subjects. RAST and RAST-inhibition assays were used to study the prevalence of specific IgE to Blomia tropicalis (Bt), Lepidoglyphus destructor (Ld), and Df. RAST results were considered positive when a serum bound greater than or equal to 1% of the total counts added; 69 atopic subjects (89.6%) were positive to Df, 66 (85.5%) to Bt, and 46 subjects (59.7%) were positive to Ld. RAST results, analyzed by regression analysis, revealed the following correlation coefficients: Df versus Bt, r = 0.59; Df versus Ld, r = 0.44; and Bt versus Ld, r = 0.52. RAST inhibition assays with a serum pool of 11 individuals highly allergic to all three mites (mean specific IgE to all mites, greater than or equal to 18.2 percent total counts bound) demonstrated considerable cross-reactivity between Bt and Ld and moderate cross-reactivity between Df and Bt and Ld. Bt, Df, and Ld possess unique, as well as common, allergens. Sensitization to Bt and Ld is very common in mite-allergic individuals in Cartagena, Colombia. PMID- 1744366 TI - Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. AB - Bronchial responsiveness to inhaled acetylcholine (ACh) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were studied in inbred Brown Norway rats actively sensitized to, and later exposed to, ovalbumin (OA). We examined animals 21 days after initial sensitization at 18 to 24 hours, or 5 days after a single challenge, or after the last of seven repeated exposures administered every 3 days. BALF was examined as an index of inflammatory changes within the lung. Animals repeatedly exposed to OA aerosols had an increased baseline lung resistance and a significant increase in bronchial responsiveness to inhaled ACh compared to control animals at both 18 to 24 hours and 5 days after the last OA exposure. Sensitized animals receiving a single OA aerosol also demonstrated bronchial hyperresponsiveness (BHR) to inhaled ACh (p less than 0.01) at 18 to 24 hours of a similar order as the multiple-exposed group. There was a significant increase in eosinophils, lymphocytes, and neutrophils in BALF at 18 to 24 hours but not at 5 days after single or multiple exposure to OA aerosol in the sensitized groups. Control animals demonstrated no changes in bronchial responsiveness, although a small but significant increase in inflammatory cells was observed compared to saline-only treated animals. There was a significant correlation between bronchial responsiveness and eosinophil counts in the BALF in the single allergen-exposed group (Rs = 0.68; p less than 0.05). We conclude that (1) BHR after allergen exposure in sensitized rats is associated with the presence of pulmonary inflammation but persists despite the regression of inflammatory cells in BALF after multiple OA exposures, and (2) this rat model has many characteristics of human allergen-induced BHR. PMID- 1744367 TI - Diagnostic laboratory immunology: a subspecialty that encompasses clinical as well as laboratory immunology. PMID- 1744368 TI - Validity of skin tests to cyclophosphamide and metabolites. PMID- 1744369 TI - IgE antibodies in tick bite-induced anaphylaxis. PMID- 1744370 TI - Physicians and death. PMID- 1744371 TI - Nepali birth practices. PMID- 1744372 TI - A Kenyan mission hospital. PMID- 1744373 TI - Future physicians' attitudes on women's reproductive rights: a survey of medical students in an American university. AB - The July 1989 US Supreme Court decision in Webster v Reproductive Health Services restricts both women's access to legal abortion and physicians' latitude when performing abortions. We surveyed 197 medical students at the Columbia University College of Physicians and Surgeons regarding their general attitudes toward abortion as well as their specific opinions concerning the Webster decision and the possible restriction of minors' access to abortion represented by three then undecided cases. Of those surveyed, 85.8% were pro-choice by self-description as compared with 14.2% pro-life. The antiabortion group was predominantly male (78.6%) and of Catholic background, while there were no significant gender and/or religious correlates among the pro-choice group. The majority of the respondents (83.2%) disagreed with either one or both stipulated restrictions of Webster and 81.4% did not support limiting minors' access to abortion in any way. Moreover, only 19.8% admitted to a change in general attitude toward abortion during their medical education. PMID- 1744374 TI - Treatment of premenstrual dysphoric symptoms in depressed women. AB - Although research has established a strong association between premenstrual dysphoric symptoms and depression, there is little data on the effect of antidepressents on premenstrual symptoms. This study compared the efficacy of three treatments--imipramine, phenelzine, and placebo--on the premenstrual symptoms of women with atypical depression who had responded to treatment for their depressive symptoms. The Premenstrual Assessment Form (PAF) was used to rate the type and degree of premenstrual symptomatology. After 12 weeks, at least two-thirds of the women on active medication showed improvement on most measures of premenstrual symptoms to the degree that they had essentially no premenstrual problems after treatment. By comparison, only half of a group of women who had responded to placebo treatment of 6 weeks duration showed such improvement. PMID- 1744375 TI - Immunohistochemical study on gastrin-releasing peptide-containing peripheral nerve fibers in rat, macaque and human. AB - Distribution of gastrin-releasing peptide (GRP)-containing peripheral nerve fibers in the respiratory organs, digestive tracts and hearts of rat, monkey and human was studied with immunohistochemical method. In the trachea, GRP immunoreactive nerve fibers were observed in the lamina propria and surrounded ducts and acini of tracheal serous glands with a basket-like appearance. In the lung, immunoreactive nerve fibers were scattered in the lamina propria of bronchi and bronchioles, and also the adventitia of veins. In the digestive organs, such as esophagus, duodenum and jejunum, numerous GRP-immunoreactive nerve fibers were distributed in the lamina propria and muscle layer; especially in the former layer where they were seen running up to the apical part of villi. GRP-containing nerve bundles and branched fibers were also observed in the atrial muscle layer. These results gave a morphological basis to future studies of the functional significance of GRP on autonomic mechanisms. PMID- 1744376 TI - Sympathoneural and skeletal muscle contributions to plasma dopa responses in pithed rats. AB - Dihydroxyphenylalanine (DOPA) in plasma has been thought to originate from sympathetic nerve endings and to reflect catecholamine biosynthesis, because changes in DOPA levels follow pharmacologically- or environmentally-induced manipulations that alter turnover of the sympathetic neurotransmitter, norepinephrine (NE). Skeletal muscle may be an additional, non-neural source of circulating DOPA. In the present study we examined sympathoneural and skeletal muscle contributions to DOPA in arterial plasma in pithed rats. Electrical stimulation of the spinal cord causes discharges of sympathetic post-ganglionic neurons, with attendant release of NE into the bloodstream, and discharges of spinal motoneurons, which causes diffuse contraction of skeletal muscle. Stimulation of the spinal cord rapidly elevated arterial plasma concentrations of NE, dihydroxyphenylglycol (DHPG), and DOPA. Pre-treatment with curare, a skeletal muscle relaxant, did not affect the NE and DHPG responses but attenuated the DOPA responses by about 50%. Administration of chlorisondamine, a ganglionic blocker, abolished NE and DHPG responses to cord stimulation, and DOPA responses were decreased by about 90%. Adrenal-demedullation did not affect the stimulation induced DOPA responses. The results demonstrate that in pithed rats undergoing spinal cord stimulation, DOPA is released into the bloodstream. Since this response is markedly inhibited after ganglionic blockade and also attenuated after skeletal muscle paralysis, the results provide indirect evidence that DOPA formed in sympathetic neurons can be stored in a non-neuronal pool and released during skeletal muscle contraction. PMID- 1744377 TI - Analysis of preganglionic nerve evoked cholinergic contractions of the guinea pig bronchus. AB - We compared cholinergic bronchial muscle contractions induced by vagus nerve (preganglionic) stimulation (VNS) with those induced by electrical field (postganglionic) stimulation (EFS). When normalized to their respective maximum response, the frequency-response curves (10 s trains) between 4 and 16 Hz were similar between VNS and EFS; however, at frequencies of 0.1-2 Hz, and at frequencies greater than 32 Hz, the VNS contractions were significantly less than EFS. When contractions elicited by 100 pulses were examined, it was found that the responses to VNS were maximal at 10-30 Hz then declined significantly to 82 35% of maximal between 40 and 200 Hz, whereas the response to EFS was essentially unchanged at frequencies up to 60 Hz and declined only to 72% of maximal up to 200 Hz. At frequencies as low as 20 Hz, the contractions evoked by VNS faded to 45 +/- 9% of the peak contraction during 60 sec of continuous stimulation, whereas those evoked by 60 sec continuous EFS remained constant. This fade observed during prolonged VNS was not blocked by the antagonists, pirenzepine and AFDX-116, at concentrations selective for M1 and M2 muscarinic receptors, respectively; nor was the fade blocked by pre-treatment with indomethacin, propranolol, phentolamine, or choline. At frequencies greater than 10 Hz, the amplitude of the preganglionic compound action potential also faded during repetitive stimulation. The results support the hypothesis that the airway ganglion neurons innervating guinea pig bronchial smooth muscle effectively filter preganglionic stimuli, especially at low and relatively high frequencies. During continuous vagus nerve stimulation, preganglionic mechanisms may also play a role in limiting the ultimate output of airway ganglia. PMID- 1744378 TI - Alpha- and beta-adrenoceptor-mediated effects on nerve stimulation-evoked release of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea pig. AB - The effect of one beta-adrenoceptor agonist and one antagonist on preganglionic nerve stimulation (PNS)-evoked increase of plasma neuropeptide Y-like immunoreactivity (NPY-LI) was studied in the pithed guinea pig, both in the presence and in the absence of the alpha 2-adrenoceptor antagonist yohimbine. Four periods of PNS (8 Hz for 30 s with 20 min intervals) were applied and the increases of mean arterial blood pressure (delta BP), heart rate (delta HR) and plasma NPY-LI (delta NPY-LI) were analysed. Infusion of the non-selective beta agonist isoprenaline (0.15 micrograms x kg-1 x min-1 i.v.) tended to reduce delta BP in response to PNS and significantly increased HR at baseline without changing the maximal HR response. Pretreatment with yohimbine (1 mg x kg-1 i.v.) significantly increased delta BP in response to PNS by about 20% without any change in basal HR being observed. The non-selective beta-adrenoceptor antagonist propranolol (5 mg x kg-1 i.v.) significantly reduced delta BP and delta HR both in the presence and in the absence of yohimbine. Isoprenaline infusion enhanced plasma delta NPY-LI by 37% in comparison with the corresponding control. This effect of isoprenaline appeared to be slow in onset and could be blocked by propranolol, which per se did not significantly change plasma delta NPY-LI. Pretreatment with yohimbine caused a three to four-fold increase in plasma delta NPY-LI, which was slightly reduced both in the presence of isoprenaline (-39%) and propranolol (-27%). In conclusion, the sympathetic neurotransmission, also with regard to neuronal NPY, seems to have two adrenergic control mechanisms: one inhibitory and one facilitatory mediated by presynaptic alpha 2- and beta adrenoceptors, respectively. The facilitatory control mechanism could not be demonstrated if the release of neuronal NPY was already greatly enhanced by alpha 2-adrenoceptors. PMID- 1744379 TI - Mucosal distortion by compression elicits polarized reflexes and enhances responses of the circular muscle to distension in the small intestine. AB - The possibility that distortion of the mucosa by compression might be a sufficient stimulus to evoke reflex responses in intestinal muscle, and that such reflexes might summate with distension-evoked (stretch) reflexes, was tested in isolated segments of guinea pig small intestine. Opened segments of intestine were pinned flat in an organ bath with, or without, distending balloons embedded in its base. Intracellular microelectrode recordings were taken from the circular muscle oral and anal to sites of application of sensory stimuli. Pressure against the mucosa, which distorts the villi without the wall being stretched, evoked polarized reflex responses in the circular muscle, consisting of excitatory junction potentials oral and inhibitory junction potentials anal to the stimulus. Distension stimuli applied by 6-mm diameter balloons that pushed against either the serosal or the mucosal surface also evoked excitatory junction potentials in the muscle oral to the stimulus and inhibitory junction potentials at anal sites. Response amplitudes were 20% greater when the distending balloon pushed against the mucosal surface. Responses to distension from the serosal side were of 20% greater amplitude when combined with mucosal distortion by compression than without such compression. It is concluded that peristaltic movements that are commonly studied in the small intestine can be consequences of reflexes elicited at the same time from mucosal distortion receptors and from stretch receptors. PMID- 1744380 TI - What does the absence of Helicobacter pylori from the antrum imply? AB - Helicobacter pylori is absent in the antrum of approximately 5, 25, and 35% of patients with duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia respectively and in the majority of asymptomatic healthy subjects from the West. The absence of H. pylori from the antrum could result from failure of exposure to (Group A) or colonization by (Group B) or temporary (Group C) or permanent (Group D) clearance of H. pylori, after initial colonization. Marked differences in the incidence of absence of H. pylori in antrum of different age group of control subjects from the West and the developing nation (such as India) are discussed. PMID- 1744381 TI - Study designs and diagnostic criteria need standardization to effectively compare worldwide ulcer trends. AB - The development of technology and worldwide communication systems has spurred the growth of international comparative studies. These comparative epidemiological studies can be fruitful if they utilize a uniform approach. We address some of the strengths and limitations of these types of studies, and suggest they should be carried out using prospectively designed protocols. PMID- 1744382 TI - Gastrin and colorectal neoplasia--chicken or egg, or both? PMID- 1744383 TI - Pancreatic pseudocyst drainage--the needle or the scalpel? AB - A sizable number of pancreatic pseudocysts resolve spontaneously. Some, however, require intervention. Surgery was the only option available for many years. Recently, however, newer methods, such as percutaneous drainage and endoscopic cystotenterostomy have been used. Percutaneous drainage is inexpensive, has a low complication rate, and is done under local anesthesia. The recurrence rate is high with a one-time needle aspiration; this rate can be reduced to less than 10% by using an indwelling catheter. All these factors tend to make percutaneous continuous catheter drainage the first choice in the management of pseudocysts that require intervention. Experience with the endoscopic technique is still limited. PMID- 1744384 TI - Patterns of dyspepsia during the course of duodenal ulcer. AB - Dyspepsia patterns during the course of duodenal ulcer (DU) were examined in terms of the number of consecutive months that patients experienced dyspepsia either intermittently or continuously, or were dyspepsia-free. The patients (n = 224) were community-based. After ulcer healing, they were evaluated every 3 months for less than or equal to 7 years. Antiulcer agents were prescribed at the physicians' discretion. We analyzed the data on a patient-month basis using a 2 state Markov chain model. The fitted mean number of consecutive months with dyspepsia and the number of months dyspepsia-free were, respectively, 1.7 and 14 in patients on antiulcer agents, and 1.5 and 9 in patients not taking them. On average, patients experienced dyspepsia during 15% of months studied if they were on antiulcer agents, and during 20% of months if not. Regardless of antiulcer therapy, dyspepsia periods were lengthened by age, especially greater than 60 years; male sex; widowhood/divorce/separation; increasing acetaminophen use; and increasing length of time since initial onset of ulcerlike dyspepsia. Dyspepsia free periods were lengthened by age greater than 70 years, and shortened by widowhood/divorce/separation and increasing cigarette consumption. These results suggest that dyspepsia occurs for less than or equal to 20% of the time in DU patients on about a yearly basis. The least dyspepsia may be expected in patients neither widowed, divorced, nor separated, in whom length of time since the initial onset of ulcerlike dyspepsia does not exceed 7 years, and who neither smoke nor use analgesics regularly. PMID- 1744385 TI - Acid and gastric ulcer pain. AB - We have shown previously that acid is one factor, although not the only one, in the pathogenesis of duodenal ulcer pain. In the present study patients with gastric ulcer were endoscoped without sedation or premedication. Under direct vision the ulcer craters were infused sequentially with 0.1 N HCl and normal saline, the sequence of infusion being randomized and double blind. Typical ulcer pain occurred in seven of 19 patients during acid infusion compared with one with saline (p = 0.023). Two patients who developed pain on acid were rechallenged after their pain disappeared, and typical pain recurred in both. Acid therefore has a definite role in the pathogenesis of gastric ulcer pain. PMID- 1744386 TI - Predicting histologic findings from endoscopic appearance of early gastric cancer. AB - In 156 cases of depressed early gastric cancer in the antrum or corpus, the differences between differentiated and undifferentiated carcinoma were studied by comparing the histological diagnosis of the resected specimens and their endoscopic appearance. We reached the following conclusions: (a) Younger patients more often had undifferentiated carcinoma (mean age: 59.8 years) than differentiated carcinoma (mean age: 77.2 years). (b) One hundred and twenty-five of 156 cases were limited to the mucosa and 29 cases were limited to the submucosa. (c) Undifferentiated gastric cancers more often invaded beyond the mucosa even when the tumor was small than did differentiated tumors. (d) Many differentiated tumors showed a smooth depressed surface, erythema at the edge of the cancer, and tapering of the gastric rugae. (e) In undifferentiated lesions the depressed tumor surface had a varied appearance, with various sized granules and nodules, as well as fading of the mucosal color and fusion of the rugae. It is important at endoscopy to consider not only whether a lesion is benign or a malignant, but also to consider its histological type. In particular, it is vital to detect small, undifferentiated gastric cancers as early as possible. PMID- 1744387 TI - Celiac sprue after surgery of the upper gastrointestinal tract. Report of 10 patients with special attention to diagnosis, clinical behavior, and follow-up. AB - The clinical onset of celiac sprue (CS) may be precipitated by upper digestive tract surgery. We report a series of 10 patients who developed CS after diverse types of peptic ulcer surgery. Six were male and 4 female. Gastrectomy with Billroth II anastomosis was performed in 5 patients, truncal vagotomy and pyloroplasty in 2, parietal cell vagotomy and pyloroplasty in 1, and vagotomy with gastrojejunal anastomosis in 2. We found that eight patients had had previous symptoms that suggested CS. Symptoms occurred early in the postoperative period. Severe diarrhea and striking weight loss were the most prominent clinical findings. The response to gluten-free diet was independent of the type of surgical procedure performed and was similar to that observed in the general celiac population. PMID- 1744388 TI - Chronic diarrhea with normal stool and colonic examinations: organic or functional? AB - To investigate whether the clinical history and basic laboratory test results can differentiate between an organic or functional cause of chronic diarrhea and thus avoid unnecessary hospital admissions and invasive procedures, we reviewed the charts of 58 adult patients admitted during 6 years because of chronic diarrhea who had normal stool and colonic examinations. The final diagnoses were irritable bowel syndrome in 34 patients, organic diarrhea in 21, and unknown cause in three. The following clinical data did not help in the differential diagnosis: age, sex, duration of diarrhea, presence of continuous diarrhea, abdominal pain, stool frequency or volume, and presence of stool mucus. Significant weight loss, nocturnal diarrhea, and the absence of tenesmus were associated with an organic cause. One or more laboratory alterations (increased erythrocyte sedimentation rate, anemia, hypokalemia, and low serum albumin level) were found in 62% of patients with organic diarrhea but in only 3% of those with functional disease; p less than 0.001. In 20 of 21 patients with organic diarrhea, an syndromic diagnosis (fat malabsorption, n = 13; inflammatory bowel disease, n = 4; and secretory diarrhea, n = 3) could be obtained with three simple tests (stool fat, rectal biopsy, and fecal water osmolality and electrolyte determination, respectively). Our study confirms that a detailed history and a few simple laboratory data can help to distinguish between functional and organic diarrhea and so avoid extensive investigation. The syndromic diagnosis of organic diarrhea can also be approximated with relatively easy tests. PMID- 1744389 TI - Can isolation of Aeromonas hydrophila from human feces have any clinical significance? AB - A total of 27,480 stool specimens from 15,548 patients with gastroenteritis were analyzed for bacterial enteropathogens during a 4-year period between 1986-89 at a major referral center in Saudi Arabia. Bacterial pathogens were isolated from 1,152 patients, Salmonella being the most frequent, followed by Campylobacter, Shigella, and Aeromonas hydrophila. The latter bacterium was found in 58 patients; seven of them were associated with other enteric pathogens, but A. hydrophila was the only organism in 51 patients. All had gastrointestinal symptoms, the most common being diarrhea (92%), followed by abdominal pain (68%), fever (37%), and vomiting (27%). Stool specimens from 1,368 control patients were negative for A. hydrophila. PMID- 1744390 TI - Elevated serum gastrin levels in patients with colorectal neoplasia. AB - Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful. PMID- 1744391 TI - Circadian periodicity and other clinical features of biliary pain. AB - We studied the time of onset and other clinical features of biliary pain in 54 patients living in Northern Italy. All patients had cholelithiasis documented by ultrasonography. The time of onset of pain followed a circadian periodicity with its peak occurring at 9:30 p.m. The typical biliary pain was steady, mostly localized in the right upper quadrant of the abdomen or the epigastrium, lasted over 1 h, and required analgesics for relief. The pain was not related to meals or body position. What precipitates biliary pain is still an enigma. PMID- 1744392 TI - Tuberculous abscess of the liver in acquired immunodeficiency syndrome. AB - We present two human immunodeficiency virus (HIV) positive patients; each was diagnosed with tuberculous abscess of the liver and treated with good clinical response. A review of the literature indicates there is no typical clinical presentation. A high index of suspicion plus special stains of tissue material are required to make the diagnosis in appropriate patients, especially because this is a treatable condition even in patients with AIDS. PMID- 1744393 TI - Transition from nutcracker esophagus to achalasia. A case report. AB - We report a middle-aged woman with nutcracker esophagus who progressed to classic achalasia in two years. Several previous reports have documented progression of nutcracker esophagus to diffuse esophageal spasm and diffuse esophageal spasm to achalasia, but the only previous report of nutcracker esophagus progressing to achalasia was in a child. Our case suggests that, in some instances, nutcracker esophagus and achalasia may share the same pathogenesis. PMID- 1744394 TI - Barrett's esophagus and achalasia. A case report. AB - A 70-year-old woman with no previous gastroesophageal surgery gave a 6-month history of dysphagia. Barium studies suggested a diagnosis of achalasia. Esophageal manometry showed absence of peristalsis and a high lower esophageal sphincter pressure. Endoscopy showed a dilated esophagus with food residue, and Barrett's esophagus was present. The association of Barrett's esophagus and achalasia must be rare. PMID- 1744395 TI - Postshunt myelopathy. AB - Postshunt myelopathy is a rare, severely debilitating syndrome complicating portosystemic shunts that is characterized by spastic paraparesis. In this report we describe a 39-year-old woman with alcoholic liver disease and postshunt myelopathy resulting in an inability to walk. The syndrome did not become manifest until eight years after construction of a side-to-side portacaval shunt. This case is compared with reported literature on the subject. PMID- 1744396 TI - Gastric mucosa in female patients with fundic glandular polyps. AB - To evaluate the characteristics of the gastric mucosa in women with fundic glandular polyps, we examined gastric acid secretion, fasting serum levels of pepsinogen I and gastrin, and gastric histology in 11 female patients with fundic polyps, and compared the results with 30 female controls without endoscopic abnormalities and 50 female patients with gastric foveolar hyperplastic polyps. No significant difference was found in gastric and secretion and fasting serum levels of pepsinogen I and gastrin between the patients with fundic glandular polyps and the control subjects. Histological examination showed that atrophic gastritis was generally not found in the patients with fundic glandular polyps. In contrast, gastric acid secretion and fasting serum levels of pepsinogen I were significantly lower and serum gastrin levels were significantly higher in the patients with foveolar hyperplastic polyps than in the other two groups. Also, patients with foveolar hyperplastic polyps had a higher prevalence and further advanced atrophic gastritis in the fundus than did the other two groups. Our investigations demonstrated that fundic glandular polyps arise from gastric mucosa without atrophic gastritis, whereas foveolar hyperplastic polyps develop from mucosa affected by atrophic gastritis, especially type A gastritis. PMID- 1744397 TI - Ultrasound imaging of pancreatico-duodenal transplants. AB - A preliminary investigation of the role of ultrasound, including color and duplex Doppler, was performed in recipients of cadaveric pancreatico-duodenal transplants. Twenty such examinations were done on three patients. Three different complications were noted: rejection, pancreatitis, and peripancreatic abscess. The mean normal resistive index (RI) was 0.71 +/- 0.12. The normal allograft anteroposterior (AP) dimension ranged from 1.5 to 2.0 cm. Intraparenchymal and main feeding vessels were demonstrated easily. RI calculations alone were not helpful in diagnosing graft rejection. However, this diagnosis can be made using a new biochemical marker, serum anodal trypsinogen. We conclude that when used in conjunction with a reliable biochemical marker for rejection (serum anodal trypsinogen), ultrasound, including color and duplex Doppler, provides an important adjunct for the rapid, inexpensive, and complete evaluation of patients with pancreatico-duodenal transplants. PMID- 1744398 TI - Changing pattern of peptic ulcer in India. An endoscopic study of 1,188 ulcer patients. AB - Earlier studies have described a profile of peptic ulcer different in developing and developed countries. In a prospective endoscopic study in India over 5 years and 8 months involving 5,948 patients with upper gastrointestinal symptoms, we detected peptic ulcers in 1,188. There were 920 patients with duodenal ulcer (DU), 185 with gastric ulcer (GU), and 83 with combinations of the two. The male to female ratio was 4.2:1. About half the ulcers were in patients age greater than or equal to 40 years. Of the 223 (18.7%) patients with peptic ulcer complications, gastrointestinal bleeding was the most common (12.7%) and gastric outlet obstruction was less common (6.2%). Endoscopic evidence of duodenal bulb deformity was seen in 74.4% of DU patients. A comparison of these results with data from previous Indian studies suggests a changing trend of peptic ulcer with respect to age and sex distribution, the ratio between DU and GU, and complications of peptic ulcer. The profile of peptic ulcer in north India today is similar to that seen in Western countries four to five decades ago. We discuss possible factors responsible for this change. PMID- 1744399 TI - Incidence and indications for cholecystectomy in a public health district of a small town in central Italy. AB - There are major differences in cholecystectomy rates between different countries. We prospectively recorded all gallbladder operations in L'Aquila, Italy (a small town in central Italy with a population of about 98,700 inhabitants) from June 15, 1987 to June 14, 1988. During that year 210 cholecystectomies were performed (women and girls = 71.4%), for a calculated yearly incidence rate of 0.212%. Cholecystectomy was elective in 85.2%, urgent in 8.6%, and was performed in the course of other abdominal operations (mainly colon cancer) in the remaining 6.2%. Half (44.3%) of the patients were operated on because of at least one episode of biliary colic, and 9.0% because of an acute complication. Respectively 16.2% and 30.5% were operated on because of dyspeptic symptoms or to prevent symptoms or complications. Gallstones were not found in six, while exploration of the common bile duct revealed gallstones in seven patients. The chemical analysis showed that 84.7% were cholesterol stones (mixed or pure). We presume that most observed differences in cholecystectomy rates between different Western countries are more likely owing to differences in indications for surgery rather than to differences in prevalence of gallstones. PMID- 1744400 TI - The classification of digestive problems into "organic" and "functional" should not be abandoned: a surgical point of view. AB - To avoid the two pitfalls of medicine, it is essential to maintain the distinction between "functional disorders" and "organic diseases." Medicalization consists in forgetting the suffering of a patient and focusing on a sick organ. This is incorrect scientifically, because it dismisses the complexity of science by deleting many variables at work, and of course it is a very inhumane way to practice medicine. Conversely, psychiatrization runs the risk of rationalization by forgetting the reality of the body. Functional disorders can be observed and the abnormalities measured by various objective ways; a positive finding does not imply there is a lesion, because many psychophysiological links have been demonstrated. Moreover, secondary gains lead some patients either to lie or submit to unnecessary surgery. PMID- 1744401 TI - Digestive diseases are functional and organic. AB - The classification of digestive problems into organic and functional is logical and helpful in medical practice. The diagnosis of a functional disorder must be positive--not only exclusive. PMID- 1744402 TI - Primary gastric lymphoma occurring in familial Mediterranean fever. PMID- 1744403 TI - Appendiceal lymphoma: a case report. PMID- 1744404 TI - Smoking habit on gastric bicarbonate secretion in patients with duodenal ulcer. PMID- 1744405 TI - Midgut malrotation with partial obstruction of duodenojejunal junction due to Ladd's bands. PMID- 1744406 TI - Pulmonary tuberculoma associated with Crohn's disease. PMID- 1744407 TI - Hemolytic anemia secondary to interferon treatment for chronic B hepatitis. PMID- 1744408 TI - Superior mesenteric vein thrombosis as a manifestation of a latent myeloproliferative disorder. PMID- 1744409 TI - Lower anterior versus abdominoperineal resection. PMID- 1744410 TI - A rare cause of severe bleeding from the anterior duodenal wall: the cystic artery. PMID- 1744411 TI - In vitro endoscopic Polaroid photography for CLO test of Helicobacter pylori. PMID- 1744412 TI - Treatment with ursodeoxycholic acid of bile reflux gastritis after cholecystectomy. PMID- 1744413 TI - Bronchoesophageal fistula complicating aphthous esophageal ulcer in AIDS. PMID- 1744414 TI - A cylindrical dilatation of the right hepatic duct in a young asymptomatic patient. PMID- 1744415 TI - Multiple gastric carcinoid in type A gastritis: clinical findings and therapeutic proposal. PMID- 1744416 TI - The role of bile salt uptake in canalicular bile formation. Transport systems and acinar heterogeneity. PMID- 1744417 TI - Propranolol and haemodynamic response in cirrhosis. AB - In the present study, we compared cirrhotic patients who had a decrease in the hepatic venous pressure gradient after propranolol intake to patients without a decrease. Twenty patients with cirrhosis and oesophageal varices were investigated during hepatic vein catheterization before and 90 min after an oral dose of 80 mg propranolol. The hepatic venous pressure gradient decreased by 12.6% (19.0 +/- 4.7 to 16.3 +/- 3.6 mm Hg, p less than 0.05). Eight (40%) out of 20 patients had a decrease of less than 10% in protal pressure (non-responders). Responders had a higher baseline cardiac index than non-responders (3.79 +/- 0.74 vs. 2.83 +/- 0.53 1.min-1.m-2; p less than 0.01). No difference in the effect of propranolol on portal pressure was observed between patients with or without ascites, or between Child-Turcotte A, B, and C class patients. Our results suggest that cirrhotic patients who respond to oral propranolol with a decrease in portal pressure are more hyperdynamic than those without a significant fall in portal pressure. PMID- 1744418 TI - Dilatation of the inferior vena cava using an expandable metal stent in Budd Chiari syndrome. AB - Caval compression secondary to hypertrophy of the caudate lobe is a well known complication of Budd-Chiari syndrome. This paper describes the use of an expandable metal stent to overcome external caval compression. Meso-caval shunting was subsequently performed with a good end result. PMID- 1744419 TI - Altered biosynthesis of gangliosides in developing biliary cirrhosis in the rat. AB - The biosynthesis of gangliosides was studied in developing biliary cirrhosis in rats 14, 28, and 42 days after bile duct obstruction. The total content and patterns of gangliosides in livers and sera, and the activity of six hepatic ganglioside synthases in a cell-free system were determined. Up to 7-fold increased synthase activities were strictly correlated in time and extent with increased total contents of gangliosides in liver and serum. In addition, altered patterns of serum gangliosides were observed. The results clearly demonstrate that the liver is the main source of elevated serum gangliosides in biliary cirrhosis in the rat. Increased hepatic biosynthesis and the secretion of gangliosides into the serum appear to be an important pathogenetic event. Alterations of hepatic enzyme activities indicate that GL2 and GM3 synthase regulate total hepatic ganglioside content. However, certain abnormalities in ganglioside patterns which were observed in the liver and sera of cirrhotic animals can not be explained by changes in hepatic enzyme activity. They indicate additional pathobiochemical mechanisms to be involved, e.g., altered hepatocellular processing and/or impaired secretion into bile. PMID- 1744420 TI - Regional sympathetic activity, severity of liver disease and hemodynamics in patients with cirrhosis. AB - One hundred and eight patients with cirrhosis (23 grade A, 46 grade B and 39 grade C, according to Pugh's classification) underwent hemodynamic studies and plasma catecholamine concentration measurements. Blood samples were withdrawn from the pulmonary artery (n = 108), the hepatic vein (n = 108), the azygos vein (n = 59), the right renal vein (n = 66), the right jugular vein (n = 34) and the femoral vein (n = 33). Plasma noradrenaline concentrations in the pulmonary artery and the hepatic vein were more elevated in grade B (607 +/- 52 and 402 +/- 42 pg/ml, respectively) and C patients (630 +/- 59 and 475 +/- 53 pg/ml, respectively) than in grade A patients (411 +/- 51 and 243 +/- 40 pg/ml, respectively). Plasma noradrenaline concentrations from these two vessels were negatively correlated with indocyanine green clearance. These results indicate that both overall and splanchnic sympathetic activities are dependent on altered hepatic function. Significant correlations were found between the wedged hepatic venous pressure and plasma noradrenaline concentrations from either the pulmonary artery, the hepatic vein or the azygos vein. These correlations indicate that both overall and splanchnic sympathetic activities are dependent on the degree of portal hypertension. Moreover, significant correlations were found between hepatic venous plasma noradrenaline concentrations and systemic hemodynamic values, suggesting that splanchnic sympathetic nervous activity could either play a role in the systemic hyperkinetic syndrome or be a consequence of this hyperkinetic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744421 TI - The acinar location of the sodium-independent and the sodium-dependent component of taurocholate uptake. A histoautoradiographic study of rat liver. AB - The acinar location of tritium-labelled taurocholate taken up from sodium containing and sodium-free perfusion media in isolated perfused rat liver was made visible by means of histoautoradiography on cryoslices at low, medium and high bile salt concentrations. In antegrade perfusion studies, in the presence of sodium, with taurocholate concentrations of 1 and 20 microM, respectively, the silver grain label was mainly restricted to acinar zones 1. At an 80 microM concentration, zones 2 and 3 were also labelled but with decreasing intensities towards the terminal hepatic venules. At 120 microM taurocholate, all acinar zones were nearly equally labelled. In the absence of sodium, antegrade liver perfusions with 1, 20 and 120 microM taurocholate resulted in an almost homogenous labelling of all acinar zones and retrograde perfusions in a silver grain density slightly decreasing towards the terminal portal venules. The results indicate that hepatocytes of all acinar zones are capable of taking up taurocholate by both a sodium-dependent and a sodium-independent pathway. The contribution of the sodium-independent uptake to the overall uptake of taurocholate increases with increasing zonal recruitment at higher concentrations. The sodium-dependent uptake, however, is always dominant. PMID- 1744422 TI - Effects of molsidomine, a long acting venous dilator, on portal hypertension. A hemodynamic study in patients with cirrhosis. AB - The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension. PMID- 1744423 TI - Conserved core protein sequences in hepatitis B virus infected patients without anti-HBc. AB - The absence of detectable anti-HBc antibodies in some hepatitis B virus (HBV) infected patients may be due to altered core-protein (HBc) sequences. To investigate this possibility we sequenced the pre-C/C-region of HBV isolated from 12 juvenile cancer patients who incurred a nosocomial infection of HBV during chemotherapy but did not develop anti-HBc antibodies or acute cytolytic episodes. The sequences demonstrated the highest sequence homology to the pre-C/C region of a previously cloned HBV genome (subtype ayw) and no deletions or striking mutations were detected. Up to 7 years after infection almost all the survivors developed low titers of anti-HBc antibodies but no clinical signs of hepatic damage. These results suggest that chemotherapy may induce a tolerance status to HBcAg, the most immunogenic HBV protein. PMID- 1744424 TI - The protective effects of SA3443, a novel cyclic disulfide, on chronic liver injuries in rats. AB - The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4- carboxylic acid (SA3443), a novel cyclic disulfide compound, on the development of chronic liver injury were studied in rats, using two types of models, carbon tetrachloride (CCl4)-induced chronic liver injury and heterologous serum (swine serum)-induced liver fibrosis. SA3443 (30-100 mg/kg, p.o.) significantly suppressed increases in serum transaminase and alkaline phosphatase activity induced by CCl4-treatment for 10 weeks. This compound also inhibited increases in hepatic lipids and hydroxyproline content in CCl4-treated rats. In the histopathological studies, treatment with SA3443 resulted in a decrease in the degree of hepatic necrosis, fibrosis and steatosis. On the other hand, 8-weeks treatment with swine serum revealed hepatic fibrosis without appearance of necrosis or fatty accumulation. In this model, SA3443 (30 mg/kg, p.o.) reduced the hepatic hydroxyproline level, and diminished the formation of connective tissue in the liver. These findings indicate that SA3443 protects the liver against chronic liver injuries induced by CCl4 and heterogeneous serum. PMID- 1744425 TI - Hepatic uptake of fluorescein, investigated by video fluorescence microscopy and digital image analysis. AB - We evaluated fluorescence microscopy combined with digitized image analysis for the investigation of fluorescein transport in the intact rat liver. The images of the surface of isolated rat livers which were perfused directly under a microscope were projected onto a silicone-intensified target camera, stored on a video tape and analyzed with a microcomputer equipped with an image digitizer. It was shown that, after correction of the day-to-day variability of the optical and electronical system, the increase in fluorescence intensity of the liver surface following fluorescein infusion depended linearly on the fluorescein concentration in the perfusion medium up to 1 mM. Since, under the conditions used, biliary secretion and metabolic influences were found to be insignificant the uptake mechanism is probably predominantly simple diffusion. PMID- 1744426 TI - Early chronic administration of propranolol reduces the severity of portal hypertension and portal-systemic shunts in conscious portal vein stenosed rats. AB - We investigated the effects of early chronic administration of propranolol on systemic and splanchnic hemodynamic changes, and the development of portal systemic shunts in conscious, unrestrained, portal vein stenosed rats. Compared to rats receiving placebo, early chronic propranolol (75 mg kg-1 day-1) administration to rats begun 3 days before portal vein stenosis and then continued for 10 consecutive days, resulted in a significant decrease in both portal pressure (11.8 +/- 1.5 mmHg) and portal-systemic shunts (48 +/- 18%) which were measured 2 to 3 h after the final dose of propranolol (15.2 +/- 1.5 mmHg and 84 +/- 5%, respectively). These beneficial effects were also observed 18 to 24 h after the final dose of chronic propranolol. In rats given propranolol continuously for 5 days starting 5 days after portal vein stenosis, portal pressure (11.8 +/- 1.2 mmHg) was significantly lower than in the placebo group but portal-systemic shunts (76 +/- 14%) were not significantly different. In rats receiving a single dose of propranolol (75 mg/kg) 10 days after portal vein stenosis and measured 2 to 3 h after propranolol administration, portal pressure (12.8 +/- 1.0 mmHg) was significantly lower than in the placebo group. Portal systemic shunts (72 +/- 17%), however, showed no significant difference from the placebo group. Similar values in portal pressure (13.3 +/- 1.2 mmHg) and portal systemic shunts (83 +/- 21%) were also observed in rats 18 to 24 h after a single dose of propranolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744427 TI - Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 1. Morphological observations. AB - Rats of two strains (BN/BiRij and WAG/Rij) were fed the ethanol-containing Lieber De Carli liquid diet supplemented with high amounts of vitamin A for 16 months. In contrast to Lieber and co-workers, who showed liver fibrosis developing within 9 months on the same diet in Sprague-Dawley rats, we were unable to demonstrate a histological and biochemical increase in liver collagen in either strain. Steatosis was present to a varying degree in both strains in ethanol-treated rats, but also in control animals. Considerable liver inflammation with focal necrosis accompanied by severe systemic inflammation was observed in 60% of the ethanol-treated WAG rats. This suggests that, at least in rats, the main effects of chronic ethanol consumption on the liver may be secondary to interference with host resistance to infections. The ethanol-high vitamin A Lieber-De Carli liquid diet does not necessarily elicit fibrosis or other characteristic histological abnormalities of human alcoholic liver disease. PMID- 1744428 TI - Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 2. Biochemical observations. AB - The inability of the 'ethanol/high vitamin A Lieber-DeCarli diet' to induce liver fibrosis in two different rat strains was further evaluated by determining changes in parameters of liver cell damage and of retinoid and lipid metabolism. In the ethanol/vitamin A-treated group, slight but constant hepatic cell damage, as indicated by elevated alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities in blood, was already observed at 6 months and maintained until the time of death at 16 months. Serum gamma-glutamyl transaminase activities were not raised. Moderate parenchymal liver cell damage was not accompanied by fibrosis. Hypertriglyceridemia or hypercholesterolemia were observed at 6-16 months of chronic alcohol administration. This response was strain dependent. In ethanol-treated rats of both strains, total liver retinoids and serum retinol concentrations were not altered. Therefore, the hypothesis that interaction between alcohol and retinoids is a major factor in the pathogenesis of alcoholic liver disease, needs to be reconsidered. PMID- 1744429 TI - Hepatitis delta virus, a model of liver cell pathology. PMID- 1744430 TI - Galen on "glands" and "spongy flesh": with special reference to an ancient mechanico-biophysical theory for superficial lymph node function. PMID- 1744431 TI - "Anti-moine; anti-biotique": the public fortunes of the secret properties of antimony potassium tartrate (tartar emetic). PMID- 1744432 TI - Disease, death, and disorder on the American frontier. PMID- 1744433 TI - Allied cooperation in malaria prevention and control: the World War II Southwest Pacific experience. PMID- 1744434 TI - Acute pancreatitis and pancreatic cancer. Biology, diagnosis, and therapy. Proceedings of the fourth meeting of the International Association of Pancreatology and the third meeting of the International Pancreatic Cancer Study Group. August 20-23, 1990, Nagasaki City, Japan. PMID- 1744435 TI - Technical guidance of endoscopic pancreatocholangiography. AB - Endoscopic pancreatocholangiography, frequently abbreviated as ERCP, is an X-ray examination of the pancreatic and biliary ducts cannulating the duodenal papilla using the fiberscope. This procedure is the only clinical examination of the pancreatic duct, and is an indispensable technique for endoscopic treatments and further investigations: endoscopic papillotomy, drainage, lithotomy, endoprothesis, pancreatoscopy, and collection and cytology of pure juice. For this examination, a skill in endoscopy is required, and the understanding of the papilla orifice, which consists of prolapsed ampullar folds in the living body, is essential. The catheter should be inserted straight toward the individual duct: the pancreatic and the biliary duct. As ultrasonography and computed tomography are advanced, the clinical roll of ERCP should be reevaluated. However, the pancreatography expresses exactly the ductal pathology, which is reflected by the background pathology of the pancreas: chronic pancreatitis, nonfusion, pancreatobiliary maljunction, small cancerous, mucous-producing tumors, and cystic lesions. PMID- 1744436 TI - Diagnosis of pancreatic cancer. Alteration of glucose metabolism. AB - Alterations of glucose metabolism occur frequently in association with pancreatic cancer. Whether diabetes predisposes or is a consequence of pancreatic cancer has not been settled. We have found that induced diabetes prevents development of pancreatic cancer in the hamster model and that genetically diabetic Chinese hamsters resist pancreatic cancer induction, whereas the nondiabetic strain does not. Also, preliminary clinical data indicates that diabetes is associated with pancreatic cancer and that the two conditions develop simultaneously. We have found diabetes or impaired glucose tolerance in 76% of the pancreatic cancer patients at the time of cancer diagnosis. The diabetic condition improved after 75% pancreatectomy. Although the preliminary observations suggest that diabetes accompanies the disorder of pancreatic cancer, additional data are needed before any conclusion can be drawn. PMID- 1744437 TI - The study of the mass screening of persons without symptoms and of the screening of outpatients with gastrointestinal complaints or icterus for pancreatic cancer in Japan, using CA19-9 and elastase-1 or ultrasonography. AB - To investigate the possibility of detecting carcinomas of the pancreas at an early stage by mass screening of persons without symptoms or by screening the outpatients with gastrointestinal complaints or jaundice, we performed a multicentral study of the mass screening of 10,162 persons at five local areas and of the outpatient screening of 4506 at 17 hospitals for pancreatic cancer in Japan for two years from 1984 to 1985, using serum CA19-9 and elastase-1 determinations or ultrasonography. Mass screening of 10,162 persons over 40 years old found only four (0.04%) cases of pancreatic cancer, including one case that was curatively treated. According to the screening of 4506 outpatients with gastrointestinal complaints or icterus, 85 (1.9%) patients were found to have pancreatic cancer. Of these 85 patients, 28 could undergo curative treatment. In addition to them, 73 (1.6%) patients with other digestive organ cancer were found. Our results suggest that the mass screening of persons without symptoms is not worthwhile in the early detection of pancreatic cancer, but outpatient screening is useful for detecting curative cancers of the pancreas. PMID- 1744438 TI - Immunotherapy with monoclonal antibody (Mab) in pancreatic adenocarcinoma. AB - Conventional therapy of pancreatic exocrine cancer is disappointing. The poor prognosis of the disease challenges development of novel therapeutic strategies. We report the results of clinical trials of the monoclonal antibody (Mab) 17-1A in patients with histologically verified unresectable pancreatic exocrine cancer. No antitumor response was seen in 18 patients treated with Mab 17-1A (500 mg) admixed with 10(9) autologous mononuclear cells, and 81% of the patients developed antimouse antibody response. Combination of recombinant gamma interferon and Mab 17-1A mixed with autologous mononuclear white cells resulted in complete response of 4-mo duration in 1 out of 25 evaluable patients and unusually stable disease from 4 to 48+ mo in another 6 patients. High intermittent doses of infused Mab 17-1A did not show any objective antitumor response and caused serious anaphylaxis in two of the patients in the trial. Because examination of six pancreatic adenocarcinoma cell lines with different doses of Mab 17-1A and IL-2 failed to augment lytic activity of mononuclear effector cells against all cancer cell lines tested, there seemed to be no rationale for pursuing clinical studies with IL-2 and Mab 17-1A in either the murine or chimeric form. Attractive therapeutic approaches include active immunotherapy with immunization using idiotypic antibodies or targeted toxicity with the use of radioimmunoconjugates, particularly 125I-labeled chimeric Mab 17 1A. PMID- 1744439 TI - Surgical treatment of pancreatic cancer. The Japanese experience. AB - Since 1973, 194 patients with pancreatic carcinoma have undergone surgery in our clinic, including 134 with carcinoma of the head of the pancreas. Of these 134 patients, resections were performed on 61 (45.5%), 49 (36.6%) of whom underwent a curative resection based on macroscopic evidence. Seven of the patients who underwent macroscopic curative resection survived for five years, giving a five year survival rate of 26.4% by the Kaplan-Meier method after excepting seven operative deaths. We compared the extent of pancreatic cancer by constructing survival curves according to the General Rules published by the Japan Pancreas Society. There was no statistical difference in survival based on tumor size or stage; however, there was a significant difference in the survival curves of so and se, being the absence or presence of the anterior capsule of the pancreas; rpo and rpe, being the absence or presence of invasion of the retroperitoneal tissue; ew(-) and ew(+), being the absence or presence of invasion at the surgical margin of resection; and n0 and n1, being the extent of lymph node metastasis. The results of this comparison suggest that extended radical pancreatectomy may be indicated for the treatment of pancreatic cancer, since the standard radical operation for pancreatic cancer may miss tumors that have spread to the retroperitoneum and extrapancreatic nerve plexus. PMID- 1744440 TI - Surgical treatment of pancreatic cancer. The Swedish experience. AB - The development at a university hospital of radical surgery for exocrine pancreatic cancer has been studied for the time period 1958-1989. It was found that the number of operations per year increased gradually, being 6.6/year during the last 5 years, giving a resection rate of 15%. The resection rate did not change during the studied time period. The size, grade of differentiation, or stage of tumor did not change. There was no significant tendency toward decreasing operation time and blood loss, although a technically more complicated operation has been done in the last 30 cases (change from total to subtotal duodenopancreatectomy). The hospital mortality rate decreased from 33 to 3%. The rate and severity of post-operative complications also strongly decreased. For the last 30 cases, there was also a prolonged long-term survival. We conclude that the total management of patients radically operated on for exocrine pancreatic cancer is today much better than it was a decade or two ago. PMID- 1744441 TI - Evidence of effective multidisciplinary treatment for resectable pancreatic cancer from the viewpoint of the CA19-9 level. AB - Nineteen patients with resectable pancreatic cancer have been treated by a multidisciplinary approach at the National Cancer Center Hospital. This therapy included extended pancreatic resection, intraoperative irradiation by 30 Gy of electrons, and intraoperative hepatic arterial or portal infusion of mitomycin C. Furthermore, postoperative chemotherapy with mitomycin C, using Seldinger's method or iv administration, was added. The study consisted of 13 patients with carcinoma of the pancreatic head and six patients with carcinoma of the body and tail. The one- and three-year survival rates for these patients were 88 and 50%, respectively. The five-year survival rate was calculated as 28%, although there is only one five-year survivor. The effectiveness of this therapy was studied by changes in Carbohydrate Antigen 19-9 (CA19-9) level. Thirteen of the 15 patients with high CA19-9 levels showed a decrease to a level less than 50 U/mL after this therapy. In the postoperative course, the patients showing a tendency of elevation of the CA19-9 level could be suspected of having cancer recurrence at this time without any physical sign or other laboratory findings. PMID- 1744442 TI - Effect of insulin treatment on the regeneration of the remnant pancreas after major pancreatectomy in dogs. AB - The effect of exogenous insulin treatment on the pancreatic regeneration after major pancreatectomy was evaluated in dogs. More than 92% of the pancreas was removed near the duodenum with the main pancreatic duct left intact. All 26 dogs developed diabetes mellitus (DM) immediately after surgery, and these dogs were divided into two groups: insulin-treated group (n = 19) and noninsulin-treated group (n = 7). All seven dogs in the noninsulin-treated group died within seven weeks after surgery, whereas all dogs in the insulin-treated group survived until the twelfth week, except for six dogs sacrificed on the seventh week, and finally seven (53.8%) of 13 dogs recovered from DM. DNA and polyamine syntheses in the remnant pancreatic tissue at the third day increased more significantly in the insulin-treated group than in the noninsulin-treated group. Sigma IRI in IV-GTT was maintained more significantly in the insulin-treated group, and the regeneration rate at the seventh week was also significantly higher in the insulin-treated group than in the noninsulin treated group. Furthermore, the regeneration rate of the remnant pancreas at seventh week correlated well with DNA synthesis and ornithine decarboxylase activity on the third day. The exogenous insulin treatment after major pancreatectomy enhanced the proliferation of the remnant pancreas within the first week, and it maintained endogenous insulin secretion, promoting pancreatic regeneration. PMID- 1744443 TI - Mechanism of acute pancreatitis. Cellular and subcellular events. AB - A membrane-bound system through which secretory and lysosomal proteins travel in a vectorial fashion is essential for the preserved integrity of pancreatic acinar cells. This system is composed of an ordered array of compartments, such as the rough endoplasmic reticulum, the Golgi complex, lysosomes, and secretory granules. As a principle, in acute pancreatitis the final steps of this transport seem to be disturbed. Caerulein-induced pancreatitis is a valuable experimental model for studying altered intracellular transport, and compartmentation of lysosomal and digestive enzymes. The formation of enlarged secretory vacuoles containing lysosomal and digestive enzymes is paralleled by the activation of lysosomes and degradation of cellular organelles in autophagosomes. On the level of secretory and autophagic vacuoles, activation of serine proteases occurs, which in addition to increasing lysosomal enzyme activities can represent the initial stage for acinar cell destruction and the development of pancreatitis. PMID- 1744444 TI - Mechanisms of acute pancreatitis. Vascular etiology. AB - Vascular mechanisms play an important but controversial role in the pathogenesis of acute pancreatitis. In experimental animals, injection of wax, powder, air, mercury, and microspheres into the pancreatic artery causes pancreatitis by end artery occlusion with resulting cellular infarction. Larger microspheres do not cause pancreatitis because collateral blood flow is preserved. Clinical evidence, such as microthrombi and atheromatous emboli in the pancreatic artery of patients with pancreatitis, supports pancreatic infarction as an etiologic agent. Experimental and clinical studies have suggested that pancreatic ischemia may also cause pancreatitis, but these studies have not been conclusive. We have compared five hours of total occlusion of the pancreaticoduodenal artery along with four hours of reperfusion to bile injection into the pancreatic duct as causes of pancreatitis. Bile injection caused a significant increase in serum amylase, activation of trypsin in pancreatic exudate, and histologic evidence of necrotizing pancreatitis. Pancreatic blood flow decreased as pancreatitis developed. Ischemia for five hours did not cause a significant increase in serum amylase or activation of trypsin in pancreatic exudate. Only edema was seen histologically, but there was no necrosis. Pancreatic blood flow increased with reperfusion. We believe ischemia aggravates, but does not initiate pancreatitis. Ischemia does not induce inflammation and necrosis in the pancreas, although infarction does. PMID- 1744445 TI - Classification of acute pancreatitis. AB - Increased knowledge of the natural history, etiology, morphology, complications and systemic response of the patient to acute pancreatitis has led to a rapid evolution in the classification of acute pancreatitis. It is recommended that the following elements be included in a classification system of acute pancreatitis: 1. A definition of acute pancreatitis and its complications based on CT scan, ultrasound, ERCP, and angiographic and histologic findings. 2. A statement regarding the etiology of the patient's pancreatitis. 3. An assessment of the patient's systemic response to his or her pancreatitis by means of APACHE II and/or Ranson's signs of severity. This system, through the use of ultrasound, CT scan with vascular enhancement, and clinical and laboratory tests, can be utilized to classify patients initially, on the day of hospital admission, with regard to etiology, morphology, and physiologic severity. Later in their hospital course, the complications of pancreatitis, e.g., fluid collections, necrosis, pseudocysts, infected necrosis, abscesses, fistulas, pancreatic, enteric, and cutaneous, pseudoaneurysm, and splenic vein thrombosis, can be added to the classification as modifiers when and if they occur. The process of the development and confirmation of theories of the origin and nature of the cosmos and evolution of concepts regarding the classification of pancreatitis have something in common. Theory generally stimulates experimental observation whose purpose is to test the theory's validity. New theories are generated when experimental observations demonstrate inconsistencies in previously held beliefs. Just as our understanding of the cosmos is undergoing constant change based on new data and new theories, so are our concepts regarding the classification of pancreatitis. PMID- 1744446 TI - Evaluation of severity of acute pancreatitis. According to a report of the cooperative national survey in Japan. AB - In the cooperative national survey of acute pancreatitis achieved by the Research Committee of Intractable Diseases of the Pancreas supported by the Japanese Ministry of Health and Welfare, 2553 cases of acute pancreatitis, except mild cases, were collected throughout Japan. The severity of disease classification systems that used both the clinical signs of the systemic and local complications and the laboratory values was evaluated. It is probable that the multiple criteria have the potential to provide improved measurement of severity and progress of acute pancreatitis. PMID- 1744447 TI - Surgery in acute pancreatitis. The Japanese experience. AB - Seventy-eight cases of severe acute pancreatitis were admitted to Mie University and its affiliated hospitals. These were subdivided into Group I (1976-1983) and Group II (1984-1989). The rate of early death was 34.8% in Group I and 9.3% in Group II. Among operated cases, peritoneal drainage alone was not effective with the worst mortality rate of 47.1%, especially in gallstone pancreatitis, with a 100% mortality rate. Early detection of infected necrosis or abscess using enhanced CT and subsequent drainage should be performed in cases of severe acute pancreatitis. A total 1182 cases of severe acute pancreatitis out of 12,309 cases of acute pancreatitis were collected in Japan by Saito et al., who belong to the Research Committee of Intractable Diseases of the Pancreas supported by the Japanese Ministry of Health and Welfare. Furthermore, 473 cases of severe acute pancreatitis in the Japanese literature reported from 1987 to 1990 were reviewed. Then, surgical indications and procedures were discussed. The incidence of necrosectomy has been increased to 10.3% from 3%, and biliary drainage procedure increased for severe acute pancreatitis. Indication of necrosectomy with or without open drainage method should be carefully evaluated in each institution. PMID- 1744448 TI - Surgery in acute pancreatitis. The United States experience. AB - Considerable controversy has existed in the United States regarding the operative management of acute pancreatitis. Recently, areas of consensus have begun to form regarding necrotizing pancreatitis and biliary pancreatitis. However, the role of surgery and endoscopy for the prevention of recurrent acute pancreatitis in patients with pancreas divisum has not as yet been established. In the United States, few areas of contemporary surgery have remained as controversial as the operative approach to patients with acute pancreatitis. Recently, however, newer methodologies have appeared that seem capable of addressing those current surgical disputes that exist in necrotizing pancreatitis, biliary pancreatitis, pancreas divisum, and in the various complications of acute pancreatitis. PMID- 1744449 TI - Regulation of pancreatic exocrine secretion. AB - The exocrine pancreas secretes throughout 24 hours. In both interdigestive and postprandial states, pancreatic secretion is regulated by neural and hormonal actions, and neurohormonal interactions. At the turn of this century, the prevailing theory of Pavlov (1) that pancreatic exocrine secretion was exclusively regulated by secretory fibers in both vagi and splanchnic nerves was refuted by Bayliss and Starling in 1902, who put forward their hypothesis that pancreatic secretion was stimulated by a circulating hormone, "secretin," which was released by hydrochloric acid from the duodenal mucosa (2). Soon, Pavlov conceded to the hypothesis of Bayliss and Starling. Pavlov adopted the theory of a dual mechanism--nervous and hormonal--of the regulation of pancreatic secretion. In recent decades, explosions of new information about old and newly discovered gut hormones or peptides and neuropeptides have resulted in a better understanding of the regulatory mechanism of the exocrine pancreas, and also opened new, exciting frontiers in the investigations of the physiology and pathophysiology of pancreatic secretion. PMID- 1744450 TI - Clinical trial with a protease inhibitor gabexate mesilate in acute pancreatitis. AB - To evaluate whether early administration of protease inhibitors could improve mortality and morbidity in acute pancreatitis (AP), we made a retrospective analysis of 23 patients with severe AP and 88 with mild to moderate AP who were treated in our institute and four affiliated medical centers during the 10-y period from 1980 to 1990. Intravenous infusion of a protease inhibitor, Gabexate Mesilate (FOY), was started within 24 h from onset of AP (early administration) in 17 patients with severe AP and 51 with mild to moderate AP. The remaining patients were put on FOY later than 24 h from onset of AP (late administration). Comparison of the mortality and morbidity between the two groups, early vs late administration of FOY, led to the following conclusions: (1) Early administration of FOY significantly improved mortality (29.4 vs 83.3%) in severe AP, although the improvement in mortality was not directly proportional to the shortening of the time lag between the onset of AP and the start of FOY, and (2) earlier administration of FOY brought about significantly earlier recovery of abdominal pain, hyperamylasemia, and leucocytosis in mild to moderate AP. PMID- 1744451 TI - Hormones and pancreatic cancer. AB - Several polypeptide hormones have been demonstrated to stimulate or inhibit cell division in the cells of the pancreas. Therefore, receptors for these hormones have been sought in pancreatic carcinomas, and several examples have been reported. In some instances, stimulation of tumor growth by the corresponding peptide has been demonstrated or growth was blocked by a receptor antagonist. Receptors and binding proteins for steroid hormones also have been reported in carcinomas of the pancreas. In experimental carcinogenesis, the growth of preneoplastic lesions and incidence of neoplasms have been influenced by both peptide and steroid hormones in some species. Experimental manipulation of sex steroid hormones has yielded both inhibition and enhancement of growth of human and rat pancreatic cancers, but thus far, clinical trials have failed to document advantageous approaches for steroid or antihormonal therapy. These observations imply that trophic or growth-inhibiting polypeptide and steroid hormones may serve as promoters or inhibitors of carcinogenesis in the pancreas, and may influence the growth of established carcinomas. Receptor blockers may provide a clinical approach for slowing the growth of some cancers. PMID- 1744452 TI - Growth factors and pancreatic cancer. AB - Cultured human pancreatic cancer cells produce a number of growth factors, including transforming growth factor-alpha (TGF-alpha). These cells also overexpress the epidermal growth factor (EGF) receptor and exhibit a parallel increase in EGF receptor mRNA levels. TGF-alpha, which binds to the EGF receptor, is more potent than EGF in enhancing the anchorage-independent growth of several pancreatic cancer cell lines, including T3M4 cells. In contrast, EGF is more efficient than TGF-alpha with respect to EGF receptor downregulation and tyrosine phosphorylation in T3M4 cells. Further, T3M4 cells recycle EGF, but markedly degrade TGF-alpha. It is suggested that the production of multiple growth factors, the overexpression of the EGF receptor, the recycling of EGF, and the attenuated ability of TGF-alpha to downregulate the EGF receptor combine to enhance the growth advantage of human pancreatic cancer cells. PMID- 1744453 TI - Diagnosis of pancreatic cancer. Serological markers. AB - Many serological markers that are widely used for delecting pancreatic cancer are discussed. Some are good indicators, but others are not. Among them, CA19-9 and SPan-1 radioimmunoassays have a higher sensitivity and specificity. However, these markers are neither tumor-specific nor pancreatic cancer-specific. Accurate understanding of their measurement made it possible to diagnose pancreatic cancer, even when the cancer was small, and to monitor the patients after treatment. PMID- 1744454 TI - Radioimmunodiagnosis of pancreatic cancer disease. AB - From a theoretical point of view, immunoscintigraphy of exocrine pancreatic cancer offers itself as a promising diagnostic method. However, the actually available clinical and experimental data point out that the indication for diagnostic application in patients with pancreatic carcinoma has to be viewed more critically than in the case of, e.g., colorectal cancer disease. The quality of imaging depends on a lot of factors, such as the cellular antigen expression, the affinity of the MAbs to the corresponding antigens expressed by the cells, tumor vascularization, tumor size, and unspecific background activity as well as on labeling techniques, the kind of antibodies used, and the technical equipment. All these factors may vary from one patient to the other and from one center to the other. In summarizing the available clinical data, we have to state that immunoscintigraphy does not allow early detection of pancreatic cancer and, consequently, does not allow screening for early stages in asymptomatic patients. Even nowadays primary diagnosis and staging should be based on the imaging methods of ultrasound, CT and/or ERCP, and angiography. With respect to detection of local recurrence and especially peritoneal carcinosis, immunoscintigraphy, however, may be superior when compared to the other imaging methods. The potential clinical value for followup and as a preinvestigation to assess the probability of effective MAb treatment has still to be evaluated in prospective clinical studies. Altogether, a lot of experimental and clinical work remains to be done to introduce immunoscintigraphy of pancreatic cancer into clinical practice as a routine method. PMID- 1744455 TI - [Maintenance of the activation of peritoneal macrophage in patients with ovarian cancer by the repeated administration of sizofiran and interferon gamma]. AB - Four patients with ovarian cancer were treated with a 20mg injection of sizofiran, a MW 450,000 beta-1,3-glucan, intramuscularly one day before and 4,7,11,14,18 and 21 days after second look laparotomy and with the administration of 2 million units of interferon gamma intraperitoneally at 0,4,7,11,14,18 and 21 days after second look laparotomy. Peritoneal macrophages were obtained from the patients by peritoneal washing with saline through an indwelled tube. The number of macrophages was increased to about 30 times after the treatment. The concentrations of interleukin 1, interferon gamma, tumor necrosis factor and prostaglandin E2 in the media of 24-hour cultured macrophage with 10 micrograms/ml of LPS were also increased throughout the treatment. These data suggest that the every 3 to 4 day treatment with sizofiran and interferon gamma maintained the activation of peritoneal macrophages which might lead to retention of the antitumor activity in patients with ovarian cancer. PMID- 1744456 TI - [Two-dimensional and Doppler echocardiographic evaluation of intrauterine blood flow dynamics in the fetuses with a ventricular septal defect]. AB - In nine fetuses with ventricular septal defect (VSD), intracardiac blood flow was observed with color Doppler ultrasound. Interventricular shunt velocity, maximum systolic velocity in the ascending aorta and pulmonary artery, trans atrioventricular blood flow velocity, and the flow pattern in the inferior vena cava were also measured with pulsed Doppler ultrasound. The cardio-thoracic ratio and ejection fraction were measured by B- and M-mood ultrasound. In all four fetuses with isolated VSD a bidirectional shunt was demonstrated. In the three normal developed fetuses time analysis showed a right (RT)-to-left (LT) shunt during systole and a LT-to-RT during diastole with maximum systolic velocities of 61cm/s, 42cm/s and 68cm/s. In the five fetuses with complexed cardiac malformation, two fetuses had a unidirectional shunt and three fetuses had a bidirectional shunt, which was a LT-to-RT during systole and a RT-to-LT during diastole. These studies indicate that although the systolic pressure in the right ventricle is slightly higher than that in the left, the pressure is almost the same in both ventricles. The presence of unidirectional shunting or a different time relationship from that of normal fetuses in bidirectional shunting would necessitate a careful check for other cardiac malformations. PMID- 1744457 TI - [Prenatal diagnosis of carbamyl phosphate synthetase deficiency by fetal liver biopsy]. AB - Carbamyl phosphate synthetase deficiency (CPSD) is one of the enzyme defects of the urea cycle and inherited as an autosomal recessive. A definitive enzymatic diagnosis of CPSD can be made by biochemical assay of liver biopsy material, but not of cultured fibroblasts. In pregnancy at risk for CPSD, prenatal diagnosis was attempted by fetal liver biopsy, performed at 22 weeks of gestation. CPS activity was present and a healthy baby was delivered at term. The technique employed for fetal liver biopsy is described together with an evaluation of its possible role in prenatal diagnosis. PMID- 1744458 TI - [The effects of pregnancy on prolactin secretion in occulted hyperprolactinemia]. AB - The changes in the maternal prolactin level during pregnancy and puerperium were studied in 14 patients with occulted hyperprolactinemia, 5 patients with functional hyperprolactinemia, and 135 women with normoprolactinemia. All of those with occulted hyperprolactinemia and functional hyperprolactinemia became pregnant through bromocriptine treatment. Higher prolactin levels were noted in occulted hyperprolactinemic patients from the first to second trimester of pregnancy, but in the third trimester prolactin levels fell to the normal control levels. This change completely resembled the change in functional hyperprolactinemic patients. Prolactin secreting capacities after puerperium returned to normal in 4 of the 5 patients with occulted hyperprolactinemia. These 4 became pregnant for the second time without any treatment. However, the other patient, whose prolactin secreting capacity was aggravated after the first puerperium, became pregnant the second time through bromocriptine treatment. These results indicate the following: 1) most cases of occulted hyperprolctinemia which may be due to functional lesions return to normal after pregnancy, 2) in rare cases of occulted hyperprolactinemia, prolactin secretion capacity is aggravated after the pregnancy, 3) it is important to observe the natural history of the patient in the treatment of occulted hyperprolactinemia. PMID- 1744459 TI - [Significance of intermittent CDDP therapy for improving long-term prognosis in patients with advanced ovarian cancer]. AB - In cases of advanced ovarian cancer, intermittent CDDP therapy (ICDDPT) was applied after the first operation and induction chemotherapy, and its efficacy and limit were studied. One cycle of this therapy involved consecutive 5 day CDDP treatment (25-30mg/body/day). The therapy was repeated at intervals of 3 months. In many cases, ovarian cancer was histologically rated as epithelial adenocarcinoma. The study included 18 cases in total. ICDDPT was applied to 13 cases in which no tumor mass was detected by second look operation (SLO) or which showed clinical remission after operation. Only 3 of these 13 cases showed recurrence, and all these 13 are still living. Of the 5 cases in which SLO disclosed a tumor mass or which did not show remission after the first operation, 2 died. When the survival rate after ICDDPT was compared by the Kaplan-Meier method with that of controls without CDDP therapy, the effectiveness of ICDDPT was demonstrated. The survival rate could therefore be improved by ICDDPT. The therapy particularly improved the long term prognosis of SLO negative cases and cases in clinical remission. It seems necessary to repeat this therapy for a long period to achieve satisfactory results. In SLO positive cases and cases without clinical remission, the therapy had only a limited effect. PMID- 1744460 TI - [The effect of immediate delivery on the fetus with reverse end-diastolic flow velocity in umbilical artery velocimetry]. AB - Reverse end-diastolic flow velocity suggests a catastrophic fetal condition. Some authors have suggested that perinatal management of these pregnancies should be more aggressive. Despite increased opportunities to use Doppler ultrasonography, guidelines for clinical management of such pregnancies have not been established. We have applied immediate delivery to 6 patients out of 7 patients who showed reverse end-diastolic flow velocity. When the study population was compared with the population of the other authors, there were no differences in gestational age at diagnosis, birth weight, or incidence of maternal hypertension. However, the study patients were delivered at significantly higher Apgar scores and had a lower perinatal mortality rate. These results suggest that immediate delivery of the fetus with reverse end-diastolic flow may be correlated with a favorable perinatal outcome. PMID- 1744461 TI - [Disorder of serum electrolytes following CAP therapy]. AB - Combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP) is one of the most effective chemotherapies for ovarian cancer. Severe vomiting induced by this treatment may cause a disorder of the serum electrolytes. Severe hyponatremia was observed in one patient who complained of convulsions and unconsciousness. Accordingly we studied the disorder of serum electrolytes in 158 courses of CAP treatment (44 patients) during the five years from 1984 to 1988. The serum electrolytes were influenced by the amount of vomiting in this study. Consequently frequent examination of serum electrolytes is necessary during this treatment. PMID- 1744462 TI - [Statistical analysis of possible causes of repeated spontaneous abortions]. AB - The possible causes of early pregnancy failure in one thousand, three hundred and seventeen women (n = 1,317) with a history of repeated reproductive wastage were analysed and the results of treatment for each etiology were evaluated. Out of 1,200 hysterosalpingographies, 188 (15.7%) congenital uterine anomalies were detected and the degree of each uterine cavity deformity was evaluated by the X/M ratio. Metroplasty was performed on 71 women with no other causes of spontaneous abortion, and more than 84% of the post-operative pregnancy were successfully maintained. One hundred and four (n = 104, 5.5%) out of 949 couples with a high incidence of reproductive failure had either a chromosomal abnormality or normal variants in the wife and/or husband. Twelve cases (n = 12, 8.1%) had a positive analysis for anticardiolipin antibody among 148 women examined. Immunotherapy utilizing the husband's lymphocytes was indicated for four hundred and seventy three (n = 473) other couples with no other abnormalities likely to induce spontaneous abortions. This treatment brought approximately 80% of pregnancies to successful termination and 199 deliveries were recorded with this immunotherapy. The present study suggests that the causes of early pregnancy failure are complex, but that most of the causes of repetitive wastage are curable after exact diagnosis and appropriate treatment. PMID- 1744463 TI - [Evaluation of fetal renal arterial blood flow waveforms with pulsed Doppler flowmetry and the correlation to estimated fetal body weight, fetal urine production rate and amniotic fluid volume]. AB - Fetal renal arterial blood flow waveforms in 69 fetuses at 28 to 41 weeks of gestation were evaluated by means of pulsed doppler flowmetry. The pulsatility index (PI) in non-retarded fetuses gradually decreased as the gestational age advanced. A negative correlation was found between the PI in non-retarded fetuses and the weeks of gestation (r = -0.676, p less than 0.01). PI of the renal artery was higher in IUGR than in non-retarded fetuses, and no negative correlation was found between the PI in IUGR and gestational age (r = -0.337). The PI in all fetuses including IUGR was negatively well-correlated to estimated fetal body weight (r = -0.633, p less than 0.01). These results showed that the PI of the renal artery has a negative correlation with fetal body weight but not with aging of the fetus. The rate of fetal urine production in 19 cases and the diameter of the amniotic pocket in 44 cases at 36 to 40 weeks of gestation were next examined. The PI of the fetal renal artery also showed a negative correlation to the urine production rate (r = -0.544, p less than 0.01) and the diameter of the amniotic pocket (r = -0.517, p less than 0.01). The results suggested that an increase in the impedance of the fetal renal artery causes a decrease in urine production. These observations indicated that the assessment of renal blood flow waveforms may be useful in evaluating the development and well-being of the fetus. PMID- 1744464 TI - [Changes in coagulability and fibrinolytic activity in the patients with ovarian hyperstimulation syndrome]. AB - Ovarian hyperstimulation syndrome (OHSS) is occasionally seen following hMG-hCG treatment in combination with a GnRH agonist. Increased coagulability and decreased renal perfusion may be life threatening in some severe cases. In order to evaluate coagulo-fibrinolytic activity, several related factors in the general circulation were examined for approximately 2 weeks after admission in 11 patients with severe OHSS. The results are as follows. 1. Fibrinopeptide A (FPA) was increased during the initial stage of OHSS followed by a gradual decrease. However, the level remained slightly higher than normal for 2 weeks after the onset of severe OHSS. 2. Fibrinopeptide B beta 15-42 (FPB beta 15-42) showed grossly similar patterns to those of FPA. 3. D-dimer levels were constantly higher than normal from the initial to the late stages of OHSS. 4. Thrombin Antithrombin III complex (TAT) was markedly increased on the days of admission followed by a gradual decrease during the following week. 5. Antithrombin III (ATIII), plasminogen and alpha 2 plasmin inhibitor (alpha 2PI) showed only minimal decreasing patterns throughout blood samplings. 6. Increases in FPA, FPB beta 15-42 and D-dimer were greater in the cases with severe hemoconcentrations. Our present data suggest that severe OHSS brings on hypercoagulability resulting in microthrombosis. In order to avoid development of coagulopathy, prophylactic treatment should be considered for patients with OHSS. PMID- 1744465 TI - [Clinical backgrounds in two kinds (absolute and relative) of mild pregnancy induced hypertension]. AB - The criteria for pregnancy induced hypertension (PIH) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute-PIH (A-PIH)" diagnosed by 1) systolic blood pressure (SBP) greater than = 140mmHg and less than 160mmHg or 2) diastolic blood pressure (DBP) greater than = 90mmHg and less than 110mmg. Another one is "Relative-PIH (R PIH)" diagnosed by 3) an increase in SBP greater than = 30mmHg compared to normal SBP or 4) an increase in DBP greater than = 15mmHg compared to normal DBP. However, there has been no report in which two types of PIH are assessed. Our hypothesis is that the pathophysiology of two types of PIH is different. The purpose of this study is to clarify the pathophysiological difference by evaluating the clinical backgrounds. We evaluated 963 nullipara and 747 multipara whose pregnancies were recorded from the 1st trimester (multiple pregnancy and pre-term delivery before 32 gestational weeks were excluded). Among 765 nullipara women, 79.4% were diagnosed as having normal blood pressure (N-group), 7.1% as A PIH, and 13.0% as R-PIH. In the multipara N-group, the figures were 632 women (84.6%), A-PIH, 4.6% and R-PIH, 10.3%. Clinical backgrounds showed that the incidence of hypertensive family history, high hematocrit (greater than = 39.0) before the 12th gestational week or obesity (Kaup index greater than = 24 before pregnancy) was significantly higher in A-PIH than in the N-group of nullipara and higher in the A-PIH than in the R-PIH and N-groups of multipara.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744466 TI - RGD-containing peptides inhibit experimental peritoneal seeding of human ovarian cancer cells. AB - A synthetic peptide containing the RGD (Arg-Gly-Asp) sequence is known to inhibit the attachment between cells and the extracellular matrix (ECM) in vitro, and also inhibit experimental pulmonary metastasis of murine melanoma cells in vivo. Prevention of peritoneal seeding by RGD-containing peptides has never previously been discussed. In this study, the inhibition of peritoneal seeding by RGD containing peptides is examined, using the in vivo experimental peritoneal seeding model with human ovarian cancer cells (JHOC-1). Intraperitoneal (i.p.) inoculation of nude mice with JHOC-1 cells soon resulted in peritoneal seeding in all of the mice. Most of them expired within 4 to 80 weeks, and none survived for as long as 10 weeks. GRGDS (Gly-Arg-Gly-Asp-Ser) sequenced synthetic peptides were administered by i.p. injection after tumor cell inoculation following some regimens, and the changes in body weight and the periods of survival of the peptides-treated and untreated mice were observed. Intraperitoneal administration of 2mg/mouse of GRGDS peptides (every 8 hours, for 4 days, beginning just after tumor cell inoculation) significantly prolonged the survival periods of the tumor implanted mice. In this study, RGD-containing peptides were found to be able to prevent in vivo experimental peritoneal seeding by continual i.p. administration. This might indicate that RGD and integrins plays a critical role in peritoneal seeding as well as in hematogeneous metastasis. PMID- 1744467 TI - [Antiphospholipid antibodies induced by immunization with husband's lymphocytes in the sera of women with unexplained recurrent spontaneous abortion]. PMID- 1744468 TI - Endothelin-1 induces inositol phosphate production in rat pregnant myometrium. PMID- 1744469 TI - [The relationship between cervical maturity at cervical cerclage and its outcome]. PMID- 1744470 TI - [A case report of lymphocytic hypophysitis complicated with visual disorder in late pregnancy and puerperium]. PMID- 1744471 TI - [Conservative surgical management of repeated ectopic pregnancy: a study of 15 cases]. PMID- 1744472 TI - [A case of diabetes insipidus occurring in early gestational stage]. PMID- 1744473 TI - [The clinical significance of lupus anticoagulant (LAC) in the pathogenesis of preeclampsia]. PMID- 1744474 TI - Trial study on endometrial polypectomy by newly developed snare under flexible hysteroscopy. PMID- 1744475 TI - Primary malignant lymphoma of the endometrium: report of a case and review of the literatures. PMID- 1744476 TI - Users' perceptions of a computerised information system in intensive care (ABICUS) on introduction and after 2 months use. AB - The aim of the present study was to assess the perceived utility of a computerised information system in an intensive care unit (ICU). Questionnaires were devised in which ICU staff indicated the ease or difficulty of obtaining and recording information (a) under the previous manual system, (b) soon after the introduction of the computerised system and (c) two months after computerisation. Results indicated the system was well received immediately and this favourable attitude persisted unchanged after two months experience. The questionnaire method also served to pinpoint some particular interface problems which are to be remedied in future versions of the system. PMID- 1744477 TI - Multivariable optimization of mechanical ventilation. A linear programming approach. AB - The proposed method aims at improved ventilatory care with reduced morbidity. It combines two important aspects of mechanical ventilation: gas exchange and lung mechanics. A single criterion was selected as optimization index of lung trauma: peak respiratory power (PRP) defined as the maximum product of pressure times flow during inspiration. Arterial blood gases reflect gas exchange and constitute the constraints of the problem. The constraints as well as the optimization index are expressed as linear functions of the input variables (frequency of breathing, tidal volume, and positive end expiratory pressure). A linear programming approach can therefore be used to determine the values of input variables that minimize PRP and at the same time keep arterial blood gases within the prescribed limits. The coefficients of the constraints and the optimization index equation are found by manipulating input variables in order to obtain four different values of PaO2, PaCO2 and PRP (there are four coefficients in each equation). The coefficients can then be calculated and the optimization procedure run. In a pilot study 5 patients suffering from diseases of varying pulmonary pathology were investigated with this method. In 4 out of 5 the ventilator treatment improved in terms of blood gas values (mean increase in PaO2 was 4.7%) and reduction of mechanical load on the lungs (mean PRP reduction was 20%). Lower PRP is accompanied by lower mean power and pressure values, which results in increased cardiac output. Presently, the main problem is the time it takes to determine the patient coefficients (approx one hour), a procedure that needs to be simplified. PMID- 1744478 TI - Computerized monitoring at Vanderbilt University status and future directions. AB - A computerized monitoring system utilizing touch screen input has been developed and tested at our university. Logical extensions of this technology include the development of a portable input device and the packaging of the physical system. Further extensions of this technology include, as necessary, the introduction of other monitoring modalities, such as respiratory and evoked potential data acquisition and analysis. PMID- 1744479 TI - Recursive programming--a valuable technique. PMID- 1744480 TI - Computer generated discharge summaries for a neonatal unit. AB - Computer generated discharge summaries are gaining in popularity. A simple and flexible method for generating neonatal summaries using commercially available software is described. PMID- 1744481 TI - Measuring the quality of critical care. PMID- 1744482 TI - The outcome index and system outcome score: a method of quality assurance through outcome analysis in the special care area. AB - A scoring system intended to assess mortality risk and permit surveillance, evaluation and comparison of medical care was developed in our Surgical Intensive Care Unit. Five simple clinical components were identified and assigned scores according to their statistically validated relationship to mortality and the summation of the component scores resulted in a daily System Outcome Score (SOS). Cluster analysis was used to divide the creation data set of 2,777 patients into suitable groupings of scores to predict mortality and the clustering was confirmed for reproducibility with a validation set of an additional 2,860 patients. Two patient care surveillance techniques were then developed. The first involved the definition of three unfavourable SOS patterns evolving during the course of a patient's admission and detection of one or more of these patterns permits identification of specific patients for whom review of care delivered may be appropriate. The second involves a global assessment of care utilizing the Outcome Index (OI) which relates overall mortality risk in the unit to the actual mortality rate over a given time period. The effectiveness of care can then be compared between different time periods within the one unit or between different units with similar patient mix. A simple menu driven program has been developed for the IBM personal computer and clones that facilitates data storage and retrieval, production of outcome reports and customization of the scoring ranges to meet local standards of performance. PMID- 1744483 TI - Postoperative biosynthetic human growth hormone increases the strength and collagen deposition of experimental colonic anastomoses. AB - This study examined the effects of preoperative treatment with 2.0 mg biosynthetic human growth hormone (b-hGH)/kg/day on the bursting strength and collagen deposition of experimental left colonic anastomoses, and of intact colon from sham-operated rats. The anastomotic bursting pressure was 55% higher in the b-hGH treated animals on day 2 (p less than 0.05) and 79% higher on day 4 (NS; p = 0.056), and the bursting wall tension was 65% higher on day 2 (p less than 0.05) and 112% higher on day 4 postoperatively (p less than 0.05), than saline injected controls. The hydroxyproline content of the anastomotic segment in the b hGH treated rats increased by 56% on day 4 (p less than 0.005) and by 30% on day 6 postoperatively (p less than 0.05), compared with controls. At 3 cm proximal to the anastomoses the defatted dry weight and hydroxyproline content of the healing colons were increased after 6 days compared with the sham-operated rats. There was, however, no difference between the b-hGH treated rats and the paired controls, indicating that growth hormone is not involved in this process. PMID- 1744484 TI - The effect of yoga on puborectalis paradox. AB - Nine patients with severe defaecation difficulties primarily considered to be due to puborectalis dysfunction (puborectalis paradox), verified by electromyography (EMG) of the striated anal sphincter muscles, were offered training in Yogic techniques of relaxation and muscle control in order to change the activity of the pelvic floor muscles during attempted defaecation. Five patients completed the training program of 20 2-hour sessions and were re-examined clinically and with EMG. One patient regained a normal EMG pattern but none of the patients improved clinically. PMID- 1744485 TI - Epidemiology of faecal incontinence in selected patient groups. AB - It is known that only a minority of patients with faecal incontinence report these symptoms to their physicians. Epidemiological estimates based on medical chart data, therefore, may contain a detection bias. To evaluate such bias in epidemiological data, we evaluated prospectively the presence of faecal incontinence in selected patient groups with a proven high incidence of such symptoms and compared it to the incidence in a group of healthy controls. If the patient acknowledged faecal incontinence in the questionnaire, the medical chart was checked to see if these symptoms had been noted during previous work-up; this was used to estimate the number of unregistered cases if the epidemiological estimate is based on medical chart data. The incidence of incontinence was significantly elevated in all patient groups as compared to the controls, but only up to 5% of patients with faecal incontinence, regardless of the underlying mechanism, had these incontinence symptoms noted in the medical charts. We conclude that for the estimation of the prevalence and incidence of faecal incontinence, data from medical charts contain a detection bias which systematically underestimates the real presence of faecal incontinence. PMID- 1744486 TI - The role of nailbed vasospasm in Crohn's disease. AB - Local cooling of the nailfold capillaries produces a typical blood flow stop reaction in patients with Raynaud's phenomenon. We applied the same test to 35 patients with Crohn's disease and compared the results with the findings in a control group of 35 healthy subjects matched for age and sex by nailfold videomicroscopy. We found a flow stop with cold exposure in 27 of the 35 patients with Crohn's disease (mean duration 38 s) in contrast to 2 of the 35 control subjects only (mean duration 12 s). There was no significant difference in skin temperature between the two groups. Intravital microscopy of nailfold capillaries revealed an evident reduction of the capillary density (p = 0.001) and crest diameter of the capillary loop (p = 0.02) compared to normal subjects. The strong association of a vasoconstrictive reaction in finger microcirculation in patients with Crohn's disease suggests a vasospastic tendency in this disorder that might manifest in the mesenteric capillaries also. This new finding of microcirculatory disturbance may play a role in the pathophysiology of Crohn's disease and be related to a general vasospastic syndrome. PMID- 1744487 TI - Transanorectal ultrasonography in the staging of anal epidermoid carcinoma. AB - Fifty consecutive patients with anal canal epidermoid carcinoma were evaluated by transanorectal ultrasonography (TRUS) at diagnosis. Forty-six patients were treated with primary radiotherapy plus bleomycin. Twenty-eight of the last 30 patients underwent, in addition, planimetric volume determination. The ultrasound findings were compared with clinical stage as assessed by digital palpation. Tumours in clinical stages T1-2 showed evidence of penetration through the anorectal muscular wall at ultrasound (UT3-4) in two-thirds of the cases. This was the case in all tumours in clinical stages T3-4. A clear correlation between tumour size, depth of invasion, and tumour volume, respectively, and residual tumour after a "pre-operative" dose of 40 Gy plus bleomycin was found. When combining clinical stage with TRUS, all tumours classified as T1-2/UT1-2 had a complete response (CR) after the first radiotherapy period, whereas the corresponding figures for those with deep invasion ultrasonographically (T1-2/UT3 4 and T3-4/UT3-4) were 64 percent and 0 percent, respectively. It thus appears that TRUS could complement digital palpation in staging anal canal carcinoma. PMID- 1744488 TI - Pouch dynamics--a simple test of ileo-anal pouch evacuation. AB - A simple technique for quantifying ileo-anal pouch evacuation has been used to compare patients with good pouch function and fully spontaneous defaecation (n = 10) to patients with a symptomatic disorder of pouch evacuation (n = 10), usually due to a pouch-anal stricture (n = 7). Pouch emptying was significantly less efficient in those with disordered evacuation (median 54% evacuated) than in those with good function (median 98% evacuated, p = 0.02) and significantly slower (median 22.4 sec vs 5.2 sec to evacuate 75% of instilled barium, p less than 0.02) even when of comparable efficiency. Testing of four further patients with high stool frequency but neither stenosis nor symptomatic difficulty with evacuation excluded a significant disorder of evacuation in three but identified inefficient emptying in the fourth. This test may prove useful in the investigation of patients with poor pouch function of uncertain origin. PMID- 1744489 TI - Extended resection in the treatment of colorectal cancer. AB - Between 1975 and 1990, 525 patients underwent resection of colorectal cancer in our unit. Of these, 38 had tumour invading adjacent structures and underwent an extended resection. Overall, there were 67 cases treated palliatively. Of these, three were in the group of 38 having an extended resection. When the groups of radical not extended (n = 423) and radical extended resections (n = 35) were compared, respective values for mortality (1.9% vs 0) and morbidity (12.8% vs 11.3%) were not different. Respective local recurrence rates (13% vs 26%) were significantly greater after extended resection. Five-year survival after extended resection was 30%, no different from the general survival rate for standard resections for T2-3 node-positive tumours. Extended resection is thus a safe and important approach for locally advanced tumours. PMID- 1744490 TI - Benign lymphoid polyposis of the colon. Report of a case in an adult. AB - A new case of benign lymphoid polyposis of the colon in an adult is presented. Relatively frequent in childhood, this disease remains exceptional in adults. The main concern is differentiation from adenomatous polyposis; the differential diagnosis can be particularly difficult for complex forms of polyposis with coexistent adenomatous and lymphoid polyps. Benign lymphoid polyposis of the colon does not appear to have any propensity for malignant degeneration, and major surgical resection is not indicated. PMID- 1744491 TI - Surgery for idiopathic megarectum and megacolon. PMID- 1744492 TI - Effect of sympathetic innervation on the human internal anal sphincter. PMID- 1744493 TI - Chronic femoral arteriovenous fistula masquerading as the postphlebitic syndrome. AB - A patient with a traumatic femoral arteriovenous fistula was misdiagnosed for 11 years as having "postphlebitic syndrome." Angiography revealed diffuse dilatation of the veins and arteries of the right lower extremity with the iliac vein measuring 16.0 cm in diameter and the cava 6.0 cm in diameter. Operative repair of the fistula has resulted in marked clinical improvement and return of the patient to fulltime employment. A history of trauma should be sought when a patient presents with unilateral chronic venous insufficiency. PMID- 1744494 TI - Organ procurement and transplantation in Louisiana: an update after 16 years. PMID- 1744495 TI - ECG of the month. Short-circuits. Wolff-Parkinson-White syndrome. PMID- 1744496 TI - Superior vena cava syndrome associated with malignant mesothelioma. AB - A 70-year-old former shipyard worker presented with dyspnea and edema of the upper thorax suggesting the diagnosis of superior vena cava syndrome. Further evaluation revealed mesothelioma with both epithelial and spindled histologic patterns. The extensive mesothelioma had invaded the adventitia of the superior vena cava, the pleura of the lungs bilaterally, the superficial myocardium, and the liver. A terminal hyercoagulable state with great vein thrombosis was also contributory. To our knowledge this is the first documented case of superior vena cava syndrome associated with malignant mesothelioma. PMID- 1744497 TI - Medicare payment reform: RBRVS ... and a whole lot more. PMID- 1744498 TI - Regulation of infectious waste in Louisiana. AB - The purpose of the article is to acquaint readers of the JOURNAL with the requirements of state regulation of infectious waste, especially as it pertains to individual physicians and their medical offices. A brief historical perspective is given, followed by a brief summary of pertinent data relating to disease transmission via infectious waste and injuries attributable to infectious waste. Suggestions which comply with the law for disposal of infectious waste from a physician's office are given. PMID- 1744499 TI - Subglottic stenosis. AB - Subglottic stenosis, a laryngeal narrowing, can be either congenital or acquired. There are various anatomic abnormalities of the cricoid that explain the congenital types. The acquired type is due to prolonged intubation in 90% of cases. Anterior cricoid split can obviate the need for a tracheotomy in the neonate with minimal nonfibrotic subglottic stenosis. Laryngotracheal reconstruction allows correction of the more severely stenotic children. Both of these procedures strive to provide an adequate airway and a satisfactory voice. PMID- 1744500 TI - Treatment of thrombosis associated with septic shock. PMID- 1744501 TI - Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-treated rabbits. AB - Endotoxin-treated rabbits produce high levels of plasminogen activator inhibitor 1 (PAI-1), which inhibits fibrinolysis by neutralizing endogenous tissue-type plasminogen activator (t-PA). These animals will develop renal fibrin deposition when infused with ancrod, an enzyme that acts directly on fibrinogen. In normal rabbits with an intact fibrinolytic system, ancrod induces hypofibrinogenemia without fibrin deposition. Rabbit PAI-1 activity can be neutralized by recombinant human t-PA or by bovine activated protein C. The present study determined the efficacy of these two agents used alone or in combination in neutralizing increased PAI-1 activity and in preventing renal fibrin deposition in a rabbit model. Male New Zealand rabbits first received intravenous endotoxin to increase PAI-1 activity. Ancrod was infused intravenously during hour 4 to 5, and the kidneys were examined at hour 5.5. Renal fibrin deposition occurred in 100% (6 out of 6) of the endotoxin-treated rabbits that received ancrod; this was reduced to 14% (1 out of 7) for rabbits receiving t-PA (170 micrograms/kg) before and during the ancrod infusion. Fibrin deposition occurred in only 12% (1 out of 8) of the rabbits that received a 10-fold lower dose of t-PA (17 micrograms/kg) combined with activated protein C (1 mg/kg) before and during the ancrod. Activated protein C at this dose completely neutralized plasma PAI-1 activity. However, low-dose t-PA and activated protein C did not prevent fibrin deposition when used as single agents, with fibrin deposition occurring in 75% and 100% of rabbits, respectively. The data indicate that activated protein C can neutralize plasma PAI-1 activity in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744502 TI - Increased urinary zinc excretion after thermal injury. AB - Urinary zinc excretion normally plays a minor role in zinc homeostasis; however, urinary zinc excretion is markedly elevated after trauma or surgery, and mechanism(s) for this zinc loss are poorly defined. In this study we evaluated multiple potential mechanisms for increased urinary zinc excretion in patients with thermal injury. We documented that patients with severe thermal injury had markedly elevated urinary zinc excretion. Above 20% total body surface area burn, however, the severity of thermal injury did not correlate with urinary zinc excretion. Serum zinc concentrations were depressed on initial evaluation and gradually increased during the hospital course, whereas peak urinary zinc excretion occurred 2 to 5 weeks after injury. Thus the depression in serum zinc concentration did not temporally relate to the observed pattern of hyperzincuria. Increased urinary zinc excretion also did not temporally relate to urinary excretion of the amino acids cysteine and histidine (both of which tightly bind zinc) nor to urinary 3-methylhistidine excretion, a marker of muscle breakdown. Urinary amylase excretion, a marker of renal tubular dysfunction, did follow the pattern of urinary zinc loss to some extent, although this correlation was not perfect. Increased oral intake of zinc via zinc supplements resulted in significantly increased urinary zinc excretion. Patients receiving total parenteral nutrition (TPN) did not have significantly increased urinary zinc excretion when compared with people receiving their total nutrient intake by mouth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744503 TI - Autologous platelet kinetics in patients with severe thrombocytopenia: discrimination between disorders of production and destruction. AB - Measurements of platelet survival and turnover in severe thrombocytopenia have proven difficult to perform and interpret. To examine the mechanisms by which platelet life span is reduced and to determine the capacity of platelet kinetic studies to discriminate between increased platelet destruction and impaired platelet production in patients with moderate to severe thrombocytopenia, we developed a modified method for labeling autologous platelets with indium-111 oxine (which increases labeling efficiency, reduces the required volumes of blood, and decreases platelet manipulation in vitro) and conducted a prospective study in 26 patients with thrombocytopenia. Seventeen patients had megakaryocytic hypoplasia (platelet count 51 x 10(9)/L, range 10 x 10(9)/L to 150 x 10(9)/L; reduced megakaryocytes in marrow smears and biopsy sample), nine patients had clinical idiopathic thrombocytopenic purpura (ITP) (platelet count 79 x 10(9)/L, range 19 x 10(9)/L to 150 x 10(9)/L; normal to increased megakaryocytes with otherwise normal marrow, and seven patients displayed the presence of autoantibodies directed against platelet glycoproteins IIb-IIIa or Ib). Although platelet life span was shortened in all patients, the average platelet survival time measured in patients with megakaryocyte hypoplasia was substantially longer than that measured in patients with ITP. Only platelet survival times measured in patients with megakaryocyte hypoplasia were predicted by the degree of thrombocytopenia. Platelet turnover was reduced in all patients with megakaryocytic hypoplasia but was variable in the patients with ITP. Platelet turnover values correlated with circulating platelet counts in patients with marrow hypoplasia but not in the patients with ITP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744504 TI - Tyrosine and N-carbamoyl-tyrosine in end-stage renal disease during continuous ambulatory peritoneal dialysis. AB - Lower-than-normal tyrosine concentrations of unexplained pathogenesis in plasma and intracellular body water have been reported in patients with chronic renal failure. We found a derivative of tyrosine that is not measured by the usual methods of amino-acid analysis because its alpha-amino group is blocked and cannot react to form other derivatives. An in vivo covalent reaction with urea derived cyanate forms alpha-amino-carbamoyl-tyrosine (N-C-Tyr) in patients with end-stage renal disease. A longitudinal study of patients with end-stage renal disease who were treated with continuous ambulatory peritoneal dialysis shows that plasma that is obtained within 4 hours of the morning meal contains 70.1 +/- 6 mumol/L of tyrosine (mean +/- SEM) and 77.2 +/- 12 mumol/L of N-C-Tyr (mean +/- SEM). Thus there is a molecule of N-C-Tyr for each molecule of tyrosine present. The carbamoylation index or ratio of N-C-Tyr to tyrosine, blood urea nitrogen, episodes of peritonitis, and changes in dialysis protocol were compared. A reduction in the number of peritoneal dialysis exchanges resulted in parallel increases in carbamoylation index and blood urea nitrogen. Altering dialysis by increasing the number of exchanges or adding supplemental hemodialysis resulted in a decrease in the carbamoylation index with a delayed decrease in blood urea nitrogen. We found a significant increase of N-C-Tyr (p = 0.005) and of the carbamoylation index (p = 0.004) during six episodes of peritonitis compared with 10 periods of no peritonitis in two patients who had multiple episodes of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744505 TI - Bacterial lipopolysaccharides alter human endothelial cell morphology in vitro independent of cytokine secretion. AB - Lipopolysaccharides derived from six bacterial species were found to alter human endothelial cell morphology in vitro in a species-dependent and dose-dependent manner. Lipopolysaccharides derived from Salmonella enteritidis (SeLPS) induced the strongest response, whereas lipopolysaccharides from Vibrio cholerae produced no effect. Cell-shape changes induced by SeLPS (10 micrograms/ml) were noticeable by 24 hours and reached a maximum by 72 hours, thus paralleling the effects produced by the recombinant cytokines interferon gamma (IFN-gamma) (10(3) U/ml), tumor necrosis factor (10(2) U/ml), and interleukin-1 (5 to 10 U/ml). Pretreatment of human endothelial cells with IFN-gamma (10(3) U/ml) for 24 hours induced an accelerated morphologic response to subsequent SeLPS (10 micrograms/ml) stimulation and vice versa, suggesting independent pathways of action. Simultaneous treatment of human endothelial cells with SeLPS and IFN gamma produced a more rapid onset of morphologic changes and a stronger overall effect. Culture medium containing polymyxin B inhibited cell-shape changes induced by lipopolysaccharides but not those induced by the cytokines. Conditioned medium generated over a 12-hour period following a 24-hour SeLPS/IFN gamma stimulation did not contain measurable cytokine antigens, nor did it induce biologic responses associated with interleukin-1, IFN-gamma, and tumor necrosis factor alpha. The results indicate that lipopolysaccharides act directly on endothelial cells as well as synergistically with IFN-gamma to alter cell morphology and may, therefore, contribute to the vascular pathology of gram negative infections. PMID- 1744506 TI - The primary structure of serum amyloid A protein in the rabbit: comparison with serum amyloid A proteins in other species. AB - Rabbit serum amyloid A (SAA) protein was isolated from acute-phase serum by ultracentrifugation, molecular seive chromatography, and ion-exchange chromatography. The complete amino acid sequence of the protein was established by sequence analysis of peptides derived from trypsin and Staphylococcus proteinase digestion of the protein. The molecule consisted of 104 amino acids and had an amino terminus that was blocked by pyrrolidonecarboxylic acid. Heterogeneity was not observed at any residue, which suggests that the material sequenced consisted of a single serum amyloid A species. The protein is highly homologous to serum amyloid A from humans and other animals, particularly in the middle portion of the molecule (positions 33 to 63), which suggests that this region may be important in its function. This highly conserved region may also contain the determinants for amyloid formation. PMID- 1744507 TI - Neutralizing antibody responses in patients with AIDS with neurologic complications. AB - Although the human immunodeficiency virus type 1 (HIV-1) is frequently isolated from the cerebrospinal fluid of infected patients, only a small percentage of patients are found to have clinical dementia or neuropathies (or both). The reasons for this remain unclear. In our study, serum neutralizing antibody titers against the human T cell leukemia virus-IIIB isolate of HIV-1 were tested in 10 patients with acquired immunodeficiency syndrome (AIDS) with neurologic complications and 20 patients with HIV infection without neurologic complications. Titers were significantly lower in the neuro-AIDS group, suggesting that impaired neutralizing antibody responses in this subpopulation of patients may be involved in the immunopathogenesis of AIDS encephalopathy. PMID- 1744508 TI - Alpha-thalassemic traits are common in the Taiwanese population: usefulness of a modified hemoglobin H preparation for prevalence studies. AB - The aim of this study was to determine the crude prevalence of alpha-thalassemia traits in Taiwan. A total of 1435 healthy employees from a statewide company were randomly screened by complete blood count determination with indices. Subjects with mean corpuscular volume less than 80 fl were analyzed by hemoglobin electrophoresis on cellulose acetate to exclude beta-thalassemia and with serum ferritin to exclude iron deficiency. Modified hemoglobin H inclusion staining was performed to confirm the diagnosis of alpha-thalassemia traits, and DNA probe studies were used to confirm the validity of this test. The overall prevalence rate of alpha-thalassemia trait was 3.4% (48 out of 1435). In persons of mainland Chinese origin, prevalence was 0.4%, and among persons of Taiwanese origin, it was 4.0% (47 out of 1171). We conclude that alpha-thalassemia traits are common genetic disorders in Taiwan and that antenatal screening is advised to reduce the frequency of occurrence of hemoglobin Bart's hydrops fetalis. The methods we used proved to be reliable and inexpensive. PMID- 1744509 TI - Endogenous platelet fibrinogen surface expression on activated platelets. AB - Intracellular platelet fibrinogen surface expression was studied in arabinogalactan-purified, resting, and thrombin-stimulated platelets. Platelet fibrinogen is derived from endocytosis of plasma fibrinogen by megakaryocytes. Like a variety of other adhesive proteins, it is stored in the platelet alpha granule. Platelet fibrinogen surface expression was studied by using the antigen binding fragments of a murine monoclonal antibody to platelet fibrinogen, F26, and an immunopurified polyclonal antifibrinogen antibody. Studies correlating platelet fibrinogen surface expression with the presence of the glycoprotein IIb IIIa (GPIIb-IIIa) complex showed that in the presence of ethylene glycol tetraacetic acid (EGTA) at 37 degrees C, neither the GPIIb-IIIa complex nor platelet fibrinogen was expressed on the surface of thrombin-activated platelets. Similar experiments performed in the presence of EGTA and calcium showed proportional expression of the GPIIb-IIIa complex and platelet fibrinogen. The addition of Arg-Gly-Asp-Ser-containing peptides, the pentadecapeptide of the fibrinogen gamma-chain carboxy terminus, or the monoclonal antibody 10E5, when directed against the GPIIb-IIIa complex before thrombin activation, inhibited 65% to 94% of the platelet fibrinogen expression, as determined with the polyclonal and monoclonal antigen-binding fragments. When these same inhibitory agents were added immediately after or 5 minutes after thrombin, the amount of inhibition decreased significantly. Similar studies with a washed platelet system revealed that when the inhibitors of platelet fibrinogen expression were added before thrombin stimulation, the degree of inhibition observed was only 24% to 38%. This suggests that the major portion of platelet fibrinogen expression involves the release of platelet fibrinogen and its subsequent binding to GPIIb-IIIa. This binding may occur within the open canalicular system or on the platelet surface; in either case, wherever the site of released platelet fibrinogen binding occurs, it can be markedly inhibited by the RGD-containing peptides and the gamma-chain fibrinogen peptides. Approximately 10% to 30% of platelet fibrinogen may be expressed prebound to a platelet receptor, or else it is released and binds to a platelet receptor other than the GPIIb-IIIa complex. PMID- 1744510 TI - Memorial minute for William B. Castle, MD. PMID- 1744511 TI - The management of oral mexiletine and intravenous lidocaine to treat chronic painful symmetrical distal diabetic neuropathy. AB - Intravenous local anesthestics administered to patients with chronic pain have been shown to provide significant levels of systemic analgesia. Furthermore, oral mexiletine which is similar in structure has been demonstrated to be efficacious in the treatment of diabetic neuropathy. It is recommended that this combined form of treatment be considered with those patients whose diabetic neuropathy is resistant to more conventional forms of treatment. PMID- 1744512 TI - Tuberculosis in the intensive care unit: a chemotherapeutic controversy. AB - A survey of 150 practicing pulmonary physicians was conducted to determine chemotherapy preferences for the treatment of the patient suffering respiratory insufficiency secondary to active nonmiliary tuberculosis. An equal sample was selected from both the private sector and academic medicine in order to determine if antituberculous agent selection differed between these two groups. The majority of the 109 physicians who responded to the questionnaire (64.2%) indicated that they would use isoniazid, rifampin, and a third agent. There was no statistical difference in the choice of ethambutol, pyrazinamide, or streptomycin as the third drug. There was no difference between university and community based physicians in the use of three drug combinations or in the selection of the specific third agent. This study suggests that, although the majority of pulmonologists responding would treat the patient with respiratory insufficiency from tuberculosis with an aggressive three drug approach, there is no consensus as to which agent should be the third drug. PMID- 1744513 TI - Upper extremity wound management: intermediate infections. AB - A careful history and physical examination, including information regarding position of the hand at the time of injury, presence of other disease, handedness, age, and occupation, are all essential to evaluate hand infection. If surgery is anticipated, antibiotics should generally be withheld until operative cultures are obtained. Infections secondary to human bite injuries are common and are usually caused by a blow of the fist to the mouth. These injuries can produce crippling sequelae, must be managed promptly and aggressively, and often require surgery. Flexor tenosynovitis, often caused by a penetrating injury, may be treated nonoperatively if the patient presents within 24 to 48 hours of onset. Older injuries always require incision and drainage of the flexor tendon sheath. Most authors agree that surgical management of dog bite wounds to the hand is essential. Cat and arthropod bites may also require surgery. PMID- 1744514 TI - Resection of renal cell carcinoma with vena cava extension using circulatory arrest. AB - Resection of renal cell carcinoma with extension into the inferior vena cava can result in massive blood loss, incomplete removal of the tumor, and systemic dissemination of malignant cells. A case is presented in which circulatory arrest with total body exsanguination permitted relatively safe resection in a bloodless operative field. PMID- 1744515 TI - Health promotion: the physician's changing role. PMID- 1744516 TI - James Given Carpenter, MD, 1854-1942. PMID- 1744518 TI - Lung diseases: where we are now and where we are going. PMID- 1744517 TI - Of consistency and of honor. PMID- 1744519 TI - Interstitial lung disease: state of the clinical art. AB - Interstitial lung diseases pose a great challenge to the clinician because of the indolent and variably active nature of these disorders and the limited number of therapeutic options. Adjunctive therapy includes supplemental oxygen in hypoxic patients, bronchodilators in patients with an obstructive lung component, and aggressive use of antibiotics in febrile patients on potent immunosuppressive therapy and suspected or confirmed infections. In younger patients who present late in their illness or deteriorate on therapy, lung transplantation is the only option. Recent advances in our knowledge of the cellular and molecular mechanisms operating in ILD and techniques which include gene amplification and cloning promise to yield more effective treatments for these diseases which currently produce a high incidence of morbidity and mortality. PMID- 1744520 TI - Asthma in the adult: management in the '90s. PMID- 1744521 TI - Recent advances in mechanical ventilatory support for adults. PMID- 1744522 TI - Restrictive covenant law in Georgia: back to the drawing board. PMID- 1744523 TI - Stereotactic radiosurgery. PMID- 1744524 TI - Of youth and the future--of attention. PMID- 1744525 TI - The Data Bank: why it should be abolished. PMID- 1744526 TI - Controlling violence: a retail approach. PMID- 1744527 TI - MAG slays the dragon: the saga of HealthCare COMPARE. PMID- 1744528 TI - The use of long-acting drugs in the treatment of rheumatoid arthritis. AB - Experience to date strongly indicates that long-acting drugs currently used in treatment of rheumatoid arthritis are very potent antiinflammatory agents which act in most cases by completely unknown mechanisms. All of them have built in but recognizable toxicity which can usually be prevented by appropriate monitoring. Although most of them offer relatively short term (up to 3 years) benefits, with the probable exception of methotrexate, nonetheless they can offer for a period of time improved function and relief of pain for many individuals. Thus, even though they do not dramatically affect the long-range outcome of the disease, they continue to offer useful benefit for patients with rheumatoid arthritis who are not responding to conservative therapy. Some of the long-acting agents are only slightly more toxic than the widely nonsteroidal antiinflammatory drugs which do have a definite risk of serious upper gastrointestinal bleeding. Currently the use of combinations as well as the continued introduction of new drugs in this class, offer hope that greater benefit than we can currently provide is within reach over the next few years. PMID- 1744529 TI - Closing the doors or selling your practice: options to consider. PMID- 1744530 TI - Rust v. Sullivan, and the future of abortion under a more conservative Supreme Court. PMID- 1744531 TI - Function and organ sparing role of radiation therapy in cancer management. PMID- 1744532 TI - CT findings of seeding tumors. AB - From 1981 to 1989 there were 43 from 154 cases of metastatic brain tumors, which seeded along the CSF pathways found in the Department of Radiology, Siriraj Hospital Medical School, Bangkok. These seeding tumors were spread from both primary intracranial (25 cases) and extracranial neoplasms (18 cases). Among the primary intracranial tumors, pineal neoplasm was the most frequent site (48%). The next rank was ependymoma (20%), medulloblastoma (16%), glioma (12%) and others (4%). The majority of extracranial neoplasms that seed in the CSF pathways were malignancy of lung (44.4%), choriocarcinoma (22%) and breast (11%). Lateral ventricle was the most frequent site of seeding (65%). The remaining tumors seeded in cisterns, leptomeninge and spinal subarachnoid space. CT is sensitive in detecting seeding tumors but not specific for each type of tumor. PMID- 1744533 TI - An outbreak of El Tor cholera in an institution for the mentally retarded in Nonthaburi, June-July 1987. AB - In June and July 1987, an outbreak of cholera caused by V.cholerae O1, biotype El Tor, serotype Inaba, occurred in an institution for the mentally retarded in Nonthaburi. Of the 447 retarded inmates, 74 were found to be infected and one died. Epidemiological investigation revealed that the inmates with severe mental retardation who ate food in their own sleeping-room were significantly (p less than 0.001) more likely to be infected than those taking food in the dining-room. We hypothesize that the liquid diet commonly served to the more severely mentally retarded may have increased the risk of infection by more rapid gastric emptying. The long average period of time for meal consumption among these individuals may have allowed the organisms to multiply to a level capable of causing disease. Contamination of food with cholera might have occurred during food handling in the kitchen or within the sleeping-room where overcrowded conditions and poor personal hygiene facilitated person-to-person spread of infection. Prompt implementation of control measures effectively terminated cholera transmission in the outbreak. PMID- 1744534 TI - Marital problems: an analysis of the causes among 115 clinical couples. AB - Among 115 couples seeking counselling for marital problems from Jan 1, 1987-Dec 31, 1989, 86.1 per cent of the consultations were initiated by the wives. Striking characteristics were as follows: 51.3 per cent of the couples had husbands who were either younger or more than three years older than their wives. A total of 62.6 per cent had dated less than bands with lower educational attainment or educational attainment more than three years higher than their wives. Sixty-two drop six had dated less than 1 year; 46.1 per cent married because of parental suggestions or had unreal expectations about marriage; 40.9 per cent did not get both partners' parents to agree to their marriage; 46.1 per cent had premarital sexual relationships, 26.1 per cent did not register for a marriage license; 26.1 per cent did not hold a wedding celebration. A history of divorce among both partners' first degree relatives was lacking in only 41.7 per cent of the couples. The three most frequent marital problems were extramarital sexual activity, lack of intimacy and not loving the partner. The wives had a marginally significant trend to face the problems arising from their partners' extramarital sexual relationships more often than the husbands. The problem of not loving the partner was found significantly more frequently during the first five years of marriage. PMID- 1744535 TI - Effects of Folia orthosiphonis on urinary stone promoters and inhibitors. AB - Yaa-Knuatmaeo or Folia orthosiphonis showed both favourable and non favourable effects of stone prevention. Uric acid and uric acid containing stone may be prevented by the increased alkalinity of the urine after drinking Orthosiphon tea. The unfavourable effect of orthosiphon being the excretion of oxalate in the urine may result in higher risk of stone formation. However, this study may or may not apply to the stone patients since it has been done only on healthy persons and all parameters were within normal limits. We feel that Orthosiphon tea may be beneficial in prevention of uric acid stone formation. This study was supported by a grant from the Medicinal Herbs Development Fund, Mahidol University. PMID- 1744536 TI - Histochemical stainings, biological cultures and therapeutic responses of granulomatous lymphadenitis in Ramathibodi Hospital-prospective study of 57 cases. AB - The study was designed to delineate the etiology of granulomatous lymphadenitis which is one of the most common lesions encountered in our routine surgical pathology practice. Fifty-seven lymph nodes diagnosed histopathologically as granulomatous lymphadenitis were cultured and stained by special histochemical stains for tuberculosis, fungus, anaerobic and aerobic bacteria. M.tuberculosis was isolated in 60-70 per cent of lesions. The remaining 30-40 per cent of the lesions failed to demonstrate any infectious agent but most of the available follow-up cases showed satisfactory response to antituberculous drugs. Ziehl Neelsen's stain showed very low sensitivity but excellent specificity and is still recommended for use to differentiate from other infectious agents in the areas where infectious agents are prevalent. PMID- 1744537 TI - An in vitro study on mefloquine/quinine in Plasmodium falciparum malaria. AB - An in vitro designed for determining sensitivity of Plasmodium falciparum strains isolated from Kanchanaburi Province, to Mefloquine/Quinine combination, was carried out. The MIC values of Mefloquine/Quinine for the P.falciparum strains were found to be 0.075/3.75 to 0.225/11.15 nM/ml. The changes observed following the drug treatment were an enlargement of the space between the outer and the inner limiting membrane of the parasitophorous vacuole. These changes were followed by cytoplasmic degeneration and vacuolation. PMID- 1744538 TI - Clinical study on antithrombotic effects of ticlopidine in ischemic stroke. AB - The investigators conducted a clinical study on antithrombotic effectiveness in ischemic stroke at Siriraj Hospital Medical School, Mahidol University from May 1987 to May 1989. Twenty-nine patients, 16 males and 13 females were enrolled in the study. The ages of the patients ranged from 30-87 years with a mean age of 63 +/- 11 years. Ticlopidine (250 mg) could significantly inhibit platelet aggregation induced by ADP and collagen within 24 hours of drug administration. After 1 week to 6 months, only aggregation by ADP was still inhibited significantly without significant effects on fibrinolytic activity and prostacyclin. Hematocrit was significantly decreased at the 1st and 2nd month of treatment. Serious side effects were skin rash and severe headache while the other common ones were dizziness, and diarrhea but these effects disappeared without discontinuing the drug. Most patients who suffered from nausea, diarrhea and headache, had temporary elevated SGPT. It may be concluded that only half of the recommended dose of ticlopidine has inhibitory effects on both phases of ADP induced aggregation without interfering with fibrinolytic activity and can maintain prostacyclin. However, it also possesses either serious or common side effects. This drug, therefore, should be used with the awareness of the clinician. PMID- 1744539 TI - Group A beta-hemolytic streptococcal type M11 sepsis and empyema: a case report. AB - A case of serious suppurative disease caused by GABHS in a previously well 2 month-old Thai female presenting with clinical features of sepsis and right pleural effusion was reported. Treatment was initially with cloxacillin and a right side intercostal drainage. When subsequent cultures of blood and pleural fluid grew GABHS; intravenous penicillin was substituted. She made an uneventful recovery. Typing of the GABHS revealed non typable T-antigen and M-protein 11 GABHS, although very sensitive to penicillin, can cause severe and rapidly progressive disease in a very young infant. This is the first case of GABHS type M11 causing pleural effusion and sepsis in an infant ever reported in Thailand. Epidemiologic study might be indicated if an epidemic should occur. PMID- 1744540 TI - Successful surgical removal of intrinsic medullar vascular malformation: a case presentation. AB - A 22-year-old man with an intrinsic arteriovenous malformation (AVM) of the medulla, who presented with recurrent subarachnoid hemorrhage and bulbar palsy was described. The successful total surgical removal of this AVM was demonstrated. The clinical, roentgenographic, pathological features and surgical approach of the brainstem vascular malformation were summarized. PMID- 1744541 TI - Vitamin B12 deficiency: report of a childhood case. AB - An 11-year-old boy who presented with anemia, premature grey hair, hyperpigmented skin, paresthesia, recurrent aphthous ulcers and epistaxis was eventually proved to be a case of vitamin B12 deficiency. Due to the paucity of this deficiency, the diagnosis may easily be delayed and overlooked resulting in unfavorable consequences. Therapeutic response to vitamin B12 was dramatic in this reported case. PMID- 1744542 TI - Polysplenia syndrome: a case with congenital heart block, infarction of a splenic mass, and a short pancreas. AB - A case of polysplenia with congenital heart block, infarction of a splenic mass, and a short pancreas was reported. The infant died of severe heart failure at the age of 28 days. Deformity of the SA node was suspected to be the cause of congenital heart block but could not be demonstrated because of some limitations of autopsy procedure. Redundant splenic pedicle might cause infarction of a splenic mass after birth. The author suggests that, in addition to the semi annular pancreas, the pancreatic anomalies of this syndrome should include the short pancreas. PMID- 1744543 TI - Effects of lidocaine and verapamil on defibrillation in humans. AB - Patients with automatic defibrillators frequently require chronic antiarrhythmic drug therapy or receive acute therapy with the onset of symptoms. The effects on energy requirements for defibrillation of lidocaine hydrochloride and verapamil hydrochloride, two commonly used antiarrhythmic agents, were examined in 20 successive patients undergoing corrective arrhythmia surgery. The minimum energy requirement for ventricular defibrillation before and 5 minutes after the administration of 150 mg of lidocaine intravenously (n = 8), or 10 minutes after 10 mg of verapamil intravenously (n = 12), were determined. Each patient was assigned to receive either verapamil or lidocaine. Three mesh coil defibrillating electrodes (Medtronic 6891, 6892) were sutured to the epicardium of the right and left ventricles. Ventricular fibrillation was induced using alternating current. After a minimum of 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. The preselected drug was then infused and the ventricular defibrillation energy was again determined after 5 or 10 minutes circulation time. Lidocaine did not alter the minimum energy for defibrillation (3.0 +/- 1.4 J vs. 3.0 +/- 1.8 J, mean +/- SD), despite plasma levels of lidocaine that averaged 13.2 +/- 1.9 mumol/l. In contrast, verapamil significantly increased (3.9 +/- 2.2 J vs. 6.5 +/- 2.9 J) the minimum energy necessary for defibrillation. The difference in defibrillation energy was significantly correlated to the fall in systolic blood pressure induced by verapamil administration (r = 0.72). These data reinforce the necessity for determining efficacy of defibrillation when medication changes are instituted. Verapamil should be used with caution in patients with automatic defibrillators and marginal defibrillation threshold. PMID- 1744544 TI - ST/HR slope and improved exercise ECG detection of myocardial ischemia in patients with suspected coronary artery disease. AB - Predictive values of ST/HR slope and ST-segment displacement during symptom limited exercise were determined in 85 patients who underwent coronary angiography for suspected coronary artery disease, using perfusional and functional radionuclide images with 99mTc-2-methoxy-isobutil-isonitrile as an index of stress-induced myocardial ischemia. ST/HR slope showed a better sensitivity than conventional stress-induced changes of ST-segment displacement (96% vs. 73%, respectively). In patients with clinical suspicion of coronary artery disease, the main result was the negative predictive value of ST/HR slope when compared with conventional ST-segment displacement (98% vs. 41%). ST/HR slope was unable to perfectly separate patients with different degrees of ischemia, however, subjects without scintigraphic signs of stress-induced ischemia and patients with ischemic impairment in three myocardial regions were correctly identified as distinct populations. In patients with a previous myocardial infarction, no difference was found between the two criteria and a wide overlap of ST/HR slope values was present. The authors conclude that ST/HR slope is useful to detect the rate of change in electric parameters during exercise and might therefore more adequately be used to separate normal from definitely abnormal responses to exercise. PMID- 1744545 TI - Digitization of electrocardiograms by desktop optical scanner. AB - The fidelity of a semiautomated technique for converting paper electrocardiogram (ECG) tracings to digital form by optical scanning was examined. Sample tracings from one nonmechanical and three mechanical ECG writers (recorders) were used. The optically scanned signals were compared with the digitized version (402 Hz, 12-bit precision) of the original analog signals using time- and frequency-domain correlation coefficients and root mean square error. A total of 261 QRS complexes and 207 RR intervals were examined in 21 leads acquired from 8 patients. When data were low-pass filtered at 25 Hz, the correlation coefficients for the 261 QRS complexes were 0.997 +/- 0.005 (mean +/- SD) for the time domain data, 0.992 +/- 0.010 for the complex frequency domain (amplitude and phase) data, and 0.998 +/- 0.002 for the power spectrum. The corresponding correlations for the 207 RR intervals were 0.993 +/- 0.008, 0.992 +/- 0.008, and 0.993 +/- 0.009. The RMS errors, normalized for signal amplitude, were 2.62 +/- 1.28 (percent +/- SD) for QRS complexes and 1.82 +/- 0.87 for RR intervals. The correlations for the mechanical ECG recorder tracings were the same or better than those of the nonmechanical recorder, and the RMS errors were generally smaller. When data were low-pass filtered at 105 Hz, the correlation coefficients ranged from 0.984 to 0.996 for the QRS complexes and 0.982 to 0.988 for RR intervals. Root mean square errors were 4.54 +/- 2.03 and 2.38 +/- 1.14, respectively. For purposes of arrhythmia analysis by QRS classification, digitization of ECG signals by optical scanning appears equivalent to acquisition via standard analog-to-digital conversion. PMID- 1744546 TI - The Brody effect revisited. AB - This paper reexamines the Brody effect, both in the far-field and in the near field approximation. It stresses the fact that near an inhomogeneity the Brody factor is not a constant but a function of space. A full documentation of this function for realistic values of the inhomogeneity as relevant to electrocardiography is included. The existence of a zone having "anomalous" Brody factors is demonstrated. Moreover, the importance for this problem of the zero reference point is stressed. PMID- 1744547 TI - Mechanisms by which calcium modulates diastolic depolarization in sheep cardiac Purkinje fibers. AB - The mechanisms by which calcium modulates diastolic depolarization (DD) in sheep cardiac Purkinje fibers were studied in vitro. Increasing [Ca]o from 2.7 mM to 10.8 mM increased both the slope and amplitude of DD, induced oscillatory potentials (V(os)), and prolonged depolarization (V(ex)). The steepening of DD occurred even in the absence of an obvious V(os). The increase in DD amplitude was due both to an increase in the maximum diastolic potential and to a less negative steady-state level. At constant [Ca]o, increasing the driving rate had effects similar to those induced by increasing [Ca]o. The increase in DD slope and amplitude was least at the slowest rates and leveled off at the fastest rates in high [Ca]o. Lowering [Ca]o decreased DD slope and amplitude, but spontaneous activity could be present during interruption of the drive. In slowly driven fibers, increasing [Ca]o to 10.8 mM initially shifted the maximum diastolic potential and steady state DD to more negative values, and subsequently shifted the latter (but not the former) to less negative values. On recovery, a transient depolarization occurred. Quiescent fibers exposed to high [Ca]o also underwent a transient hyperpolarization and a subsequent depolarization, whereas reciprocal effects occurred when [Ca]o was lowered. It is concluded that [Ca]o modulates DD through several different mechanisms and that most (but not all) modifications induced are brought about by changes in [Ca]i. PMID- 1744548 TI - Different effects of reoxygenation on the electrical activity of ventricular muscle. AB - Response of a hypoxic and acidotic (HA, with exogenous lactate) ventricular muscle tissue to subsequent reoxygenation in the absence of substrate (0 mM dextrose) was different from that of a Purkinje fiber. The K+ concentration in this solution (4.6 mM) was slightly higher than that in Tyrode solution (2.7 mM). The observed effects of reoxygenation of such a ventricular tissue were also variable. The ventricular muscle tissue exhibited the following different responses on reoxygenation after hypoxia and acidosis: (1) arrhythmias, without much depolarization of the membrane potential, (2) oscillatory after-potentials (OAPs) during the late diastole, which lessened in amplitude as the time of reoxygenation increased, but no arrhythmias, or (3) a pronounced slowed phase of repolarization (hump), but no arrhythmias. These different effects of reoxygenation did not occur if concentration of K+ in HA was very much higher than 4.6 mM. Common to these three different responses was the prolongation of the action potential durations during reoxygenation at the 50% and 90% levels of repolarization (APD50 and APD90) and a slight increase in the resting tension after 30-40 minutes of reoxygenation. Some of the observed responses of ventricular muscles were well mimicked by increasing extracellular calcium, but the different and variable effects of arrhythmias, OAPs, and prolonged APD require further analysis. PMID- 1744549 TI - Effects of myocardial infarction on cardiac electrical field properties using a numerical expansion technique. AB - This study was undertaken to quantify basic cardiac electrical field properties using the Karhounen-Loeve (K-L) numerical expansion technique after experimental myocardial infarction. Transmural anterior myocardial infarction was produced in seven dogs by injection of liquid latex into the anterior descending artery; posterior myocardial infarction was produced in five dogs by injection of the circumflex artery. Body surface potentials from 84 electrodes were recorded during sinus rhythm prior to and 1 week after infarction. Electrical field properties during the QRS, ST, and QRST intervals were computed by the K-L method based upon areas calculated for each lead. The ratio of the sum of magnitude of the first three eigenvectors to the sum of all computed eigenvectors expressed as a percentage was used as a measure analogous to field dipolarity. Values before infarction were high during the QRS (97.1% +/- 2.0%, mean +/- 1SD), ST (96.0% +/- 5.1%), and QRST (97.7% +/- 2.7%) intervals, with no significant difference between the three periods. After infarction, the ratio during QRS decreased significantly, with lower values after posterior (61.9% +/- 11.7%) than after anterior (91.1% +/- 6.0%) infarction (p less than 0.001). Values during ST and QRST intervals were not significantly changed by infarction. Spatial patterns of the first eigenvector indicated that the derived QRS area electric field is directed away from the myocardial lesion for both anterior and posterior infarcts. Thus, experimental myocardial infarction produces significant changes in cardiac electrical field properties as measured by the K-L technique. PMID- 1744550 TI - Comparison of the effects of pirmenol and lidocaine on intraventricular conduction in canine myocardial infarction. AB - Effects of pirmenol hydrochloride and lidocaine hydrochloride on intraventricular conduction were examined in the infarcted heart of anesthetized dogs. The effects of the drugs on the excitation induced by ventricular stimulations were determined with coupling intervals between 150 and 1,000 ms. Effects of the drugs on the His bundle electrocardiograms were also examined. Pirmenol in doses of 1-5 mg/kg prolonged the conduction time in the infarcted zones over a wide range of coupling intervals. Pirmenol at 5 mg/kg blocked the delayed conduction at a short coupling interval in the infarcted zones. The effect of pirmenol on the conduction time in the normal zone was slight. Lidocaine in doses of 3 and 10 mg/kg prolonged the conduction time in the infarcted zone at a short coupling interval. Pirmenol did not significantly prolong PQ or AH interval. In conclusion, pirmenol selectively depressed the delayed conduction in the infarcted zone, which could result in a reentrant pathway. The effect of pirmenol on delayed conduction was dependent on the coupling interval and was quite different from that of lidocaine. PMID- 1744551 TI - Analysis of bites on three-dimensional vectorcardiography after coronary artery ligation in dogs. AB - The serial changes in the QRS loops of vectorcardiograms were investigated following ligation of a branch of the left anterior descending artery (LAD) by the three-dimensional rotation method in 18 dogs. Concave inflections of the QRS loop, defined as "bites," were best delineated when the loop was viewed from a left cranial or right caudal direction. Bites appeared 48 +/- 8 minutes after LAD ligation in all of the dogs, and their development was closely related to the temporal changes in the % sigma R and QRS point score on a standard 12-lead electrocardiogram. Q waves were not observed on the electrocardiograms in 9 dogs. In the remaining 9, they appeared 117 +/- 18 minutes after LAD ligation. The bite duration, area, and amplitude were compared with the anatomical extent of the infarcts. A significant positive correlation was found between bite duration and infarct size. The detection of bites on the three-dimensionally rotated vectorcardiogram appears to have a high sensitivity for anterior myocardial infarction and could potentially become a useful diagnostic tool. PMID- 1744552 TI - Active immunization with a synthetic peptide region of growth hormone: increased lean tissue growth. AB - The effects of active immunization against a specific peptide region of GH (sequence 134-154) were examined in a species relevant for animal production in vivo. Peptide-immunized lambs exhibited significant increases in carcass protein and water contents and consequently increased carcass weight. The comparatively smaller increases in carcass water and protein contents which occurred in GH treated lambs were offset by decreased fat accretion. Thus, even though peptide immunization improved lean tissue growth, it did not simply enhance all actions of GH or mimic exogenous hormone administration. This is the first definitive demonstration that endogenously produced antibody may enhance endogenous hormone activity and performance in animals. PMID- 1744553 TI - The form and function of the Leydig cells in hypophysectomized rams treated with pituitary extract when spermatogenesis is disrupted by heating the testes. AB - The morphology and in-vivo function of the Leydig cells were studied in rams when spermatogenesis had been disrupted by a single exposure of the testes 20 days earlier to a temperature of about 42 degrees C for 45 min. To avoid complications due to changed negative feedback from the testes to the pituitary with consequent changes in the degree of gonadotrophic stimulation, ten of the animals (five heated and five unheated) were surgically hypophysectomized when the testes were heated and then treated twice daily with pituitary extract. Six intact rams (three heated and three unheated) were also studied. The heat-affected testes were about half the size of the unheated testes, and blood plasma flow was closely related to testis weight. There were no differences in the testosterone concentrations in spermatic venous blood, testicular lymph or rete testis fluid, or in oestradiol in spermatic venous plasma from heated or unheated testes. Consequently, testosterone secretion by the heat-affected testes was markedly reduced, and the concentrations in jugular blood were also lower in the heat affected rams than in controls. The volume of the interstitial tissue was less in absolute terms in the heat-affected rams, but it made up a greater fraction of the testes. The absolute volume of the blood plus lymph vessels, and their fraction of the interstitial tissue were lower in the heat-affected testes, although there was no effect on their volume as a fraction of the whole testis. The heat-affected testes of the hormone-treated rams had fewer Leydig cells, but each cell was larger; no equivalent difference was found in the intact rams. However, the dose of pituitary extract chosen was somewhat excessive, as there were higher than normal concentrations of FSH, LH and testosterone in jugular blood plasma, of testosterone and oestradiol in testicular venous blood plasma and of testosterone in rete testis fluid in the hormone-treated hypophysectomized rams. The testes of the unheated hypophysectomized rams increased in size by about 20% during treatment with pituitary extract, although testicular blood plasma flow was lower per unit weight of testis. The absolute volume of each Leydig cell and the total volume in absolute terms and as a fraction of the interstitial tissue was greater in the hormone-treated than in the untreated rams, but not the volume as a fraction of the whole testis. The total number of Leydig cells was higher in the hormone-treated unheated rams than in all the other rams taken together.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744554 TI - Growth hormone regulation of insulin-like growth factor-I mRNA in rat adipose tissue and isolated rat adipocytes. AB - The effects of hypophysectomy and hormonal replacement therapy on insulin-like growth factor-I (IGF-I) mRNA in rat adipose tissue and adipocytes were studied. The effects of GH and IGF-I in vitro on IGF-I mRNA and IGF-I production were also studied in cultured rat adipocytes. Male rats were hypophysectomized at about 50 days of age and given replacement therapy with cortisol (400 micrograms/kg per day) and thyroxine (10 micrograms/kg per day). GH was given as a single i.v. or s.c. injection and also as a continuous s.c. infusion for 6 days. Epididymal fat pads were excised and used either for isolation of adipocytes or for determination of IGF-I mRNA in adipose tissue. A solution hybridization assay was used. The IGF-I mRNA content of adipocytes was analysed either immediately after isolation or after short-term (2-3 days) culture with or without GH or IGF-I. Hypophysectomy resulted in a marked decrease in IGF-I mRNA in both tissue and cells. Replacement therapy (in vivo) with cortisol and thyroxine alone had no effect, whereas additional treatment with GH caused a dose-dependent increase in IGF-I mRNA. IGF-I mRNA was also increased after a continuous s.c. infusion of GH. A single i.v. injection of GH (100 micrograms) resulted in an increase in IGF-I mRNA after approximately 2 h, with maximal levels around 6 h after the injection. In cultured adipocytes, addition of GH to the culture medium increased IGF-I mRNA in a dose-dependent manner and a marked increase was observed with a concentration of GH of 1 ng/ml. Addition of IGF-I (100 ng/ml) had no effect. The increase in IGF-I mRNA after addition of GH (100 ng/ml) was detectable after 3 h. The concentration of IGF-I in the culture medium was increased 24 h after the addition of GH. These results demonstrate that GH induces IGF-I mRNA in both adipose tissue and isolated fully differentiated adipocytes and that this increase in IGF-I mRNA results in increased IGF-I production. PMID- 1744555 TI - Effect of administration of human chorionic gonadotrophin on criteria used to assess testosterone administration in athletes. AB - Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0.8 and 1.2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography-mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport. PMID- 1744556 TI - Effects of exogenous growth hormone on growth and body composition in genetically selected mice. AB - The effects of exogenous GH on growth and body composition were investigated in lines of mice selected for high or low body weight (P-lines) or high or low body fat (F-lines). Mice from all lines were given daily injections of recombinant bovine GH or a placebo for 21 days from 4 weeks old. They were killed and various organ weights measured. There was no consistent effect of GH on organ weights. In all lines of mice the rate of weight gain and final weight increased in response to GH. In both lines selected for body fat, GH treatment decreased fat content. The low body weight mice also became less fat, but in the high body weight mice GH treatment increased fat percentage. The results indicate that the differences in growth rate and body composition observed in these lines are not due to differences in responsiveness to GH. PMID- 1744557 TI - Thyroidal inhibition of chicken pituitary growth hormone: alterations in secretion and accumulation of newly synthesized hormone. AB - Hypothyroidism reduces GH synthesis and release in several mammalian species, in which thyroid hormone directly stimulates GH gene transcription. In contrast, hypothyroidism stimulates GH secretion in birds, in which thyroid hormone directly inhibits pituitary GH release. We have, therefore, investigated the effects of thyroid status on the accumulation of newly synthesized GH in the pituitaries of 8- to 10-week-old Leghorn cockerels in vitro and in vivo. The incorporation of [35S]methionine into immunoprecipitable GH ([35S] GH) was increased, over a 4-h incubation period, in glands from birds made hypothyroid by injections of methimazole (50 mg/kg day for 10 days) in comparison with glands from vehicle-injected controls. Treatment with tri-iodothyronine (T3, 100 micrograms/kg per day for 10 days) in vivo did not significantly alter the accumulation of [35S]GH in vitro but did block the release of [35S]GH in response to a GH secretagogue (thyrotrophin-releasing hormone; exposure to 280 nmol/l for 30 min) and reduced immunoassayable pituitary GH content. Pretreatment of glands from euthyroid birds with T3 (100 nmol/l) in vitro (for 20 h) reduced the basal accumulation of [35S]GH as well as that induced by another GH secretagogue (GH releasing factor; 100 nmol/l) during a 6-h labelling period. These results show that, unlike the generally stimulatory action of thyroid hormone in mammals, in birds, T3 exerts a direct inhibitory effect on the accumulation of newly synthesized pituitary GH. PMID- 1744558 TI - Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. AB - This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1-1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P = 0.001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feedback. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744559 TI - Regulation of prostate growth. PMID- 1744560 TI - Growth regulation in the gobiid teleost, Gillichthys mirabilis: roles of growth hormone, hepatic growth hormone receptors and insulin-like growth factor-I. AB - Studies of the teleost Gillichthys mirabilis were undertaken to assess the role of GH in regulating hepatic GH receptors, insulin-like growth factor-I (IGF-I) activity and cartilage growth. Hypophysectomized G. mirabilis were injected with saline vehicle or with 10, 100 or 1000 ng tilapia GH (tGH)/g every other day for 2-3 weeks. Growth, judged by increased body weight and length, was inhibited by hypophysectomy and stimulated by increasing tGH doses. Hepatic GH receptors, measured by 125I-labelled tGH binding, were decreased 50% by hypophysectomy. An additional dose-dependent reduction in binding was observed 24 h after tGH injection, but MgCl2 stripping of membranes suggested receptor occupation by exogenous tGH. IGF-I activity, measured by 35SO4 incorporation into oral cartilage explants in vitro, was decreased 50% by hypophysectomy and increased to 200% of intact control levels after injection of 1000 ng tGH/g. In a second experiment, 35SO4 incorporation by oral cartilage from hypophysectomized fish injected with 10, 100 or 1000 ng tGH/g was stimulated to intact control levels. Effects of feeding and tGH injection on in-vitro responsiveness of oral cartilage to recombinant bovine IGF-I (rbIGF-I; 10-1000 ng/ml) were also assessed. Oral cartilage from fed fish showed a parabolic dose-response curve, whereas oral cartilage from starved fish had a lower basal rate of 35SO4 incorporation and a linear dose-response relationship. Oral cartilage from hypophysectomized G. mirabilis showed a significantly attenuated response to rbIGF-I which was restored by tGH injection, suggesting that the GH status of the animal is important for sensitivity of target tissue to IGF-I. Because of its similarity to other vertebrate systems, G. mirabilis presents a good teleost model of growth regulation and of the functions and interactions of GH and IGF-I. PMID- 1744561 TI - Effect of thyroid state and cold exposure on rat liver mitochondrial protein mass and function. AB - The effects of thyroid state on liver mitochondrial protein mass was investigated in rats at 24 and 4 degrees C, as was oxidative phosphorylation using substrates which represent the final catabolic products of the metabolic fuels. In rats at 24 degrees C, a significant increase in mitochondrial protein mass (about +40%) was observed only in hyperthyroid animals, while a significant increase due to cold exposure was found in hypothyroid (+45%) and euthyroid (+35%) rats. In rats at 24 degrees C, hypothyroidism significantly decreased the oxidation of glutamate and palmitoyl carnitine but not of pyruvate, while hyperthyroidism only increased the oxidation of palmitoyl carnitine. On the other hand, exposure to cold significantly increased the oxidation of glutamate and pyruvate only in the presence of tri-iodothyronine. Our results underline not only the fact that a simple and single hypothesis for thyroid effects cannot be adopted, but also that any study concerning oxidative metabolism should be carried out using different substrates and involving different pathways of oxidation. PMID- 1744562 TI - Interaction between cortisol and arachidonic acid on the secretion of LH from ovine pituitary tissue. AB - In several species, glucocorticoids act directly on the pituitary gonadotroph to suppress the gonadotrophin-releasing hormone (GnRH)-induced secretion of the gonadotrophins, especially LH. A mechanism for this action of these adrenal steroids has not been established, but it appears that the glucocorticoids influence LH release by acting on one or more post-receptor sites. This study investigated whether glucocorticoids disrupt GnRH-induced LH release by altering the liberation of arachidonic acid from plasma membrane phospholipids, a component of GnRH-induced LH release. Using perifused ovine pituitary tissue, it was established that exposure of gonadotrophs to 1-1000 nmol cortisol/l for 4 h or longer significantly reduced GnRH-stimulated LH release with the maximal inhibitory effect being observed after 6 h of exposure to cortisol. This suppressive effect of cortisol could be reversed by administration of arachidonic acid, which in its own right could stimulate LH release from ovine pituitary tissue. Furthermore, the inhibitory effect of cortisol on GnRH-stimulated LH release could be directly correlated with decreased pituitary responsiveness to GnRH-stimulated arachidonic acid liberation, consistent with our hypothesis that glucocorticoids can suppress GnRH-induced secretion of LH by reducing the amount of arachidonic acid available for the exocytotic response of GnRH. PMID- 1744563 TI - Modulation of immunoreactive epidermal growth factor levels in the submandibular gland, pancreas, liver, kidney and gastrointestinal tract of suckling rats by cortisone and tri-iodothyronine. AB - Suckling rats exhibit age-dependent differences in epidermal growth factor (EGF) levels in several organs. The present studies evaluated the effects of two hormones known for their maturative effect on suckling rats, cortisone and tri iodothyronine (T3), on immunoreactive EGF levels in specific organs. Suckling rats were administered cortisone (5 mg/100 g body weight per day) or T3 (50 micrograms/100 g body weight per day) on days 8, 9, 10 and 11 after birth, and killed on day 12. Submandibular glands, kidneys, pancreas, liver and gastrointestinal tract mucosa and lumen were assayed for immunoreactive EGF by a species-specific radioimmunoassay. Low levels of EGF in the submandibular glands were increased slightly by both T3 and cortisone treatment. Cortisone evoked a tenfold increase in EGF in the pancreas, but had no effect on levels in the kidney or liver. In contrast, T3 evoked a sixfold increase in the EGF level in the kidney, but had no effect on levels in the pancreas or liver. Hormonal administration had no effect on EGF levels in the stomach. Within the intestinal tract, cortisone had no effect on the luminal EGF content of the duodenum, jejunum or ileum, but caused a decrease in the midjejunum. T3 evoked a decrease in the luminal EGF content of the ileum. The effect of cortisone on mucosal EGF content varied between regions; an increase was seen in the duodenum with a decrease in the midjejunum and ileum. T3 administration resulted in a significant decrease in EGF only in the mucosa of the ileum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744564 TI - Regulatory functions for inhibin and activin in human ovaries. PMID- 1744565 TI - The control of FSH secretion in the larger domestic species. PMID- 1744566 TI - The influence of vanadate on insulin counter-regulatory hormones in obese fa/fa rats. AB - Vanadate has been shown to improve glucose homoeostasis in mildly glucose intolerant and severely insulin-resistant fa/fa rats. The present study examined whether changes in insulin counter-regulatory hormones contribute to this beneficial effect of vanadate. Since oral administration of Na3VO4 caused a decrease in food intake and stopped the increase in body weight, vanadate-treated fa/fa rats were compared with both controls with food available ad libitum and pair-fed rats. Slightly lower plasma glucose levels were maintained in conjunction with markedly lower plasma insulin levels in vanadate-treated rats, and this effect was not simply due to the smaller body weight of the animals. Compared with control rats, treatment with vanadate affected neither basal plasma glucagon levels nor the increase in glucagon levels observed after insulin induced hypoglycaemia or after i.v. injection of arginine. Compared with pair-fed rats, treatment with vanadate prevented the fall in basal plasma glucagon and its exaggerated rise in response to insulin that mere food restriction produced. Plasma corticosterone levels were high in fa/fa rats. Vanadate and pair-feeding similarly decreased basal plasma levels of corticosterone as well as nocturnal corticosteronuria. Thus the attenuation of the hypercorticism of fa/fa rats results from the reduction in body weight gain rather than from a specific action of vanadate. Vanadate did not influence urinary excretion of noradrenaline, an index of neural sympathetic activity, but prevented the increase in adrenaline excretion, an index of adrenal medulla activity, that was produced by food restriction in pair-fed rats. In conclusion, vanadate administration has no or little specific effects on three major insulin counter-regulatory hormones. This reinforces the suggestion that the beneficial effects of vanadate on glucose homoeostasis in fa/fa rats are mainly due to a correction of insulin resistance in peripheral tissues. PMID- 1744567 TI - Regulation of DNA synthesis in chicken adipocyte precursor cells by insulin-like growth factors, platelet-derived growth factor and transforming growth factor beta. AB - Adipose tissue growth can occur by both hypertrophy and hyperplasia. The capacity for adipocyte hyperplasia in vivo resides in a population of fibroblast-like adipocyte precursor cells but the regulation of the proliferation of these cells by growth factors has not been well characterized. This study was designed to determine the effects of the insulin-like growth factors (IGF-I and IGF-II), platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF beta 1) added alone or together on the proliferation of primary adipocyte precursor cells in vitro. Adipocyte precursor cell proliferation measured by [3H]thymidine incorporation into DNA was stimulated by all of these growth factors and was particularly marked with PDGF. IGF-I or IGF-II added together with TGF-beta 1 produced a greater than additive response and the effect of PDGF was synergistic with that of IGF-I at certain concentrations. Stimulation of proliferation of some cell types by TGF-beta has been linked to the secondary production of PDGF but the evidence we have suggests that this is unlikely in chicken adipocyte precursors. DNA synthesis in response to TGF-beta 1 required only a short exposure to the peptide, and conditioned medium from chicken adipocyte precursor cells previously exposed to TGF-beta had no effect on DNA synthesis when added to fresh batches of cells. Addition of TGF-beta 1 together with PDGF produced a synergistic effect whereas an additive effect would be expected if PDGF mediated the effect of TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744568 TI - Effects of a sustained release formulation of the gonadotrophin-releasing hormone agonist histrelin on serum concentrations of gonadotrophins and oestradiol, and ovarian LH/human chorionic gonadotrophin receptor content in the rat. AB - Pituitary and ovarian function were studied during the loss and recovery of oestrous cyclical activity in rats following treatment with a sustained release formulation of the gonadotrophin-releasing hormone (GnRH) agonist [imidazole benzyl-D-His6,Pro9-ethylamide]-GnRH (histrelin). A single s.c. injection of microencapsulated histrelin (10-300 micrograms peptide/kg) induced a dose dependent disruption of normal oestrous cyclical activity with a persistent dioestrous-like vaginal cytology. In preliminary studies, pituitary gland stimulation and desensitization were demonstrated when serum LH and FSH levels were greater 1 week after administration of 10 micrograms microencapsulated histrelin/kg compared with 300 micrograms microencapsulated histrelin/kg. Changes in pituitary and ovarian function were assessed over time following injection of microencapsulated histrelin (100 micrograms peptide/kg). LH secretion was maximal within 8 h and then gradually declined, remaining at dioestrous levels from days 7 to 28. Serum oestradiol concentrations remained low and rose above dioestrous levels only on day 28. In contrast, ovarian LH/human chorionic gonadotrophin (LH/hCG) receptor content fell within 8 h and, after a nadir on day 7, slowly returned to dioestrous levels by day 28. The increase in ovarian LH/hCG receptor content preceded any significant change in pituitary gonadotrophin secretion, indicating a differential pattern of recovery for pituitary and ovarian function. Subsequent studies tested the possibility that these temporal differences in pituitary and ovarian function may result from histrelin acting directly on these tissues. Treatment with histrelin microcapsules (300 micrograms peptide/kg) prevented any increase in LH secretion in response to a GnRH challenge 3 days later, indicating a direct action of histrelin on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744569 TI - Production and purification of biologically active recombinant tilapia (Oreochromis niloticus) prolactins. AB - Recombinant expression vectors carrying tilapia prolactin-I or -II (tiPRL-I or tiPRL-II) cDNA were constructed and the tiPRL-I and II proteins were produced in E. coli as inclusion bodies. These inclusion bodies were dissolved in 6 mol urea/l. Refolding of the proteins was followed by SDS-PAGE under non-reducing conditions so as to visualize the oxidized state of the molecules. Proteins tiPRL I and tiPRL-II were purified by gel filtration and ion-exchange chromatography. The N-terminal sequence and bioactivities of both purified proteins were then analysed. Recombinant tiPRL-I and tiPRL-II induced a significant rise in plasma calcium levels as well as in mucocyte density in the abdominal skin epithelium. When tested on kidney membrane, both proteins exhibited potency in competing with 125I-labelled tiPRL-I for binding sites, but tiPRL-I seemed to be more potent than tiPRL-II in competing for these sites. The results obtained for the biological activities tested suggest that both recombinant prolactins were correctly refolded and had retained the full biological activity previously observed with the natural hormone preparations extracted from the animals. PMID- 1744570 TI - Oestradiol-17 beta induces the major vitelline envelope proteins in both sexes in teleosts. AB - During growth of the ovarian follicle, the teleost oocyte becomes surrounded by an acellular coat, the vitelline envelope. The nature, origin and number of the vitelline envelope proteins in fish appear to vary with species. In this work, polyclonal antibodies directed against vitelline envelope proteins from rainbow trout, brown trout and turbot were used to show that oestradiol-17 beta induces the major vitelline envelope proteins in juveniles, both males and females, from different species. The fact that males can synthesize vitelline envelope constituents shows that the origin of these proteins is not confined to the ovary. The vitelline envelope of rainbow trout eggs consists of three major proteins, designated alpha (60 kDa), beta (55 kDa) and gamma (50 kDa). The amino acid composition of each of the three proteins indicated that the three proteins are alike and the suggestion that these proteins represent a separate class of structural proteins is sustained. PMID- 1744571 TI - Transferrin inhibits aromatase activity of rat granulosa cells in vitro. AB - The effect of transferrin on basal and FSH-stimulated aromatase activity of granulosa cells from immature female rats treated with diethylstilboestrol (DES) was examined in vitro by a radiometric method. The basal activity of the enzyme was very low after 3 days of incubation. Treatment with FSH (20 ng/ml) resulted in a 9.6-fold increase in activity, whereas coincubation with increasing doses of transferrin (3-300 micrograms/ml) produced a dose-dependent inhibition of FSH stimulated aromatase activity with a projected minimal effective dose of less than 2 micrograms/ml. A time-course study showed that the inhibitory effect of transferrin on aromatase activity has become significant at 48 h of incubation. The inhibitory action of transferrin on the enzyme complex was further confirmed by showing that the FSH dose-response curve was significantly suppressed by concomitant treatment with 100 micrograms transferrin/ml with a maximum suppression of 54.1% at a dose of 30 ng FSH/ml. The possibility that transferrin may act through a non-specific inhibitory effect seems unlikely, as no changes in cell number and DNA content per well were observed. In fact, protein synthesis was enhanced after treatment with transferrin. Aromatase activity, stimulated by several promoters of cyclic AMP (cAMP), such as prostaglandin E2 (PGE2), forskolin and 8-bromo-cAMP, was significantly suppressed by 100 micrograms transferrin/ml (36.6, 47.4 and 23.4% inhibition respectively), suggesting that the effect of transferrin on FSH action may involve a site(s) distal to cAMP generation. These findings indicated that transferrin, present in follicular fluid, may play an important role in the regulation of granulosa cell differentiation. PMID- 1744572 TI - Oral insulin in diabetic dogs. AB - Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia. PMID- 1744573 TI - Regulation of testicular insulin-like growth factor-I in pubertal growth hormone deficient male rats. AB - GH plays a major role in pubertal growth, effects mainly mediated by stimulation of insulin-like growth factor-I (IGF-I) production by the liver. However, the role of GH in the regulation of pubertal onset, spermatogenesis and fertility is still under debate. GH and FSH have, in addition, been implicated in the regulation of IGF-I production by Sertoli cells in a number of studies, although conflicting results have been reported. The interpretation of studies using GH deficient mutant mice has been complicated by the presence of additional defects in the hypothalamic-pituitary-gonadal axis of these animals. We have therefore used GH-deficient mutant male rats with no other documented hormonal deficiencies to study the effect of GH administration on somatic and testicular development, circulating and testicular IGF-I concentrations and testicular histology. Body weights in GH-deficient rats substituted with GH were not significantly different from untreated or GH-treated normal rats and were significantly higher than body weights in untreated dwarf rats. Similarly, circulating IGF-I concentrations in GH-treated GH-deficient rats were not significantly different from those in untreated or GH-treated normal rats but were significantly higher than circulating IGF-I concentrations in untreated dwarf rats. No differences in testicular IGF-I concentrations were observed in any of the groups studied. Testicular weights remained low in both untreated and GH-treated GH-deficient animals compared with control animals but spermatogenesis was qualitatively and quantitatively normal in all groups at the end of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744574 TI - Effects of beta-endorphin and naloxone on corticosterone and cortisol release in the newt (Triturus carnifex): studies in vivo and in vitro. AB - The effects of beta-endorphin and its receptor antagonist, naloxone, on corticosterone and cortisol production in male and female Triturus carnifex were studied in vivo and in vitro. In the in-vivo experiment, the animals were injected s.c. with beta-endorphin and/or naloxone, and killed after 15, 30, 90 and 360 min. In the in-vitro experiment, interrenal tissues, with and without added pituitary, were incubated with beta-endorphin and/or naloxone for 15, 30, 60 and 120 min. The data obtained in vivo and in vitro from males and females were in agreement. Treatment with beta-endorphin caused a significant decrease in corticosterone and cortisol release, while naloxone induced an increase in the two corticosteroids at the same times as the decrease caused by beta-endorphin. The combined beta-endorphin plus naloxone treatment did not change corticosterone and cortisol levels. These results suggest that, in Triturus carnifex, opioids are involved in the regulation of the hypothalamo-pituitary-interrenal axis. In particular, the in-vitro results indicate a direct effect of opioids on interrenal steroidogenesis. PMID- 1744575 TI - Bombesin and bradykinin increase inositol phosphates and cytosolic free Ca2+, and stimulate DNA synthesis in human endometrial stromal cells. AB - The present studies were carried out to investigate the effect of several growth factors on human endometrial stromal cells. In human endometrial stromal cells, bombesin and bradykinin provoked an increase in intracellular free Ca2+ and in labelled inositol phosphates when pre-incubated with [3H]myoinositol. Some or possibly all of the initial increase in intracellular free Ca2+ represented a mobilization of Ca2+ from intracellular stores and the second phase of the response depended on Ca2+ influx from the extracellular medium. [3H]Thymidine was added to human cultured endometrial stromal cells with bombesin, bradykinin, epidermal growth factor (EGF), prostaglandin F2 alpha, vasopressin and platelet derived growth factor. Bombesin, bradykinin and EGF stimulated the incorporation of [3H]thymidine into DNA in quiescent cells. In conclusion, bombesin and bradykinin are growth factors which activate phospholipase C in human endometrial stromal cells, while EGF stimulates DNA synthesis without the activation of phospholipase C. PMID- 1744576 TI - B cell tolerance in mice transgenic for anti-CD8 immunoglobulin mu chain. AB - To analyze in vivo the induction of B cell tolerance against a T cell surface antigen, we generated transgenic mice expressing an anti-CD8.2 mu heavy chain gene. We show that self-specific B cells are efficiently tolerized if they express the membrane-bound form of the transgenic mu chain on their surface but that they can escape tolerization if they express only the secreted form. In the latter, we find an enhanced expression of anti-CD8.2 antibodies after polyclonal B cell activation. As a result, transgenic anti-CD8.2 antibodies bind to the CD8+ T cells but they did not induce their elimination. Furthermore, we observed the preferential expression of a limited subset of endogenous light chains with the transgenic mu chain. This suggests a positive or negative selection for particular heavy and light chain combinations in B lymphocytes. PMID- 1744577 TI - Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. AB - A new neutrophil-activating peptide, termed ENA-78, was identified in the conditioned media of stimulated human type II epithelial cell line A549. In response to stimulation with either interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha), ENA-78 was produced and secreted concomitantly with IL-8, GRO alpha, and GRO gamma. ENA-78 consists of 78 amino acids [sequence; see text] and has a molecular weight of 8,357. It has four cysteines positioned identically to those of IL-8 and analogues, and thus belongs to the CXC family of peptides. ENA-78 is related to neutrophil-activating peptide 2 (NAP-2) and GRO alpha (sequence identity, 53% and 52%, respectively) and IL-8 (22% identity). Like NAP-2 and GRO alpha, ENA-78 stimulates neutrophils, inducing chemotaxis, a rise in intracellular free calcium and exocytosis. Cross-desensitization experiments indicate that ENA-78 acts through the same type of receptors as IL-8, NAP-2, and GRO alpha. PMID- 1744578 TI - Hemolysis of human erythrocytes is a new bioactivity of gangliosides. AB - Using sheep erythrocytes and liposomes, an inhibitory effect of gangliosides has been shown on the activation of the alternative pathway of complement. However, in studies using human erythrocytes, we found that gangliosides had hemolytic activity that was possibly mediated through activation of the alternative pathway. Pretreatment of human erythrocytes obtained from healthy volunteers or paroxysmal nocturnal hemoglobinuria (PNH) patients with a ganglioside mixture purified from human erythrocytes enhanced their susceptibility to homologous human complement, and resulted in dose-dependent hemolysis. The enhancement was more marked in PNH erythrocytes than control cells. Protease treatment of the ganglioside mixture did not change its hemolytic activity, but sialidase treatment abolished the activity. Among the major erythrocyte gangliosides, II3NeuAc-LacCer (GM3) was the most potent hemolytic agent. Gangliosides purified from bovine brain were also active, while neither nonsialylated glycosphingolipids, the ceramide moiety, or sialic acid alone were active. Sialic acid residues in the ganglioside molecules were essential to this activity, but the amount of the residue or the source of the gangliosides seemed not to be important. Several treatments inhibiting the alternative but not classical complement pathway markedly reduced the ganglioside hemolytic activity. This novel bioactivity of gangliosides was thus suggested to be mediated partly by activation of the alternative pathway. PMID- 1744579 TI - Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41. AB - Human immunodeficiency virus type 1 (HIV-1), in contrast to animal retroviruses such as murine leukemia virus, is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independent of antibody, and C3b deposition facilitates infection of complement receptor-bearing cells. Using gel exclusion chromatography on Sephacryl S-1000, purified virions were found to bind 125I-labeled C1q, but not 125I-labeled dimeric proenzyme C1s. Virions activated the C1 complex, reconstituted from C1q, proenzyme C1r, and 125I-labeled proenzyme C1s, to an extent comparable with that obtained with immunoglobulin G ovalbumin immune complexes. To determine the activating viral component, recombinant viral proteins were used: in the solid phase, soluble gp41 (sgp41) (the outer membrane part of gp41, residues 539-684 of gp160) bound C1q, but not dimeric proenzyme C1s, while gp120 was ineffective. In the fluid phase, sgp41 activated the C1 complex in a dose- and time-dependent manner, more efficiently than aggregated Ig, but less efficiently than immune complexes. To localize the C1 activating site(s) in gp41, synthetic peptides (15-residue oligomers spanning amino acids 531-695 of gp160) were used. Peptides covering positions 591-605 and 601-620 and, to a lesser extent, positions 561-575, had both the ability to bind C1q and to induce C3 deposition. These data provide the first experimental evidence of a direct interaction between the C1 complex and HIV-1, and indicate that C1 binding and activation are mediated by specific sites in gp41. PMID- 1744580 TI - Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment. AB - The effects of biweekly intravenous injections of Staphylococcus Enterotoxin B (SEB) into autoimmune MRL-lpr/lpr (MRL/lpr) mice were investigated. Rather than causing the expansion of V beta 8+ T cells, SEB administration resulted in the reduction V beta 8+, CD4-CD8- "double-negative" (DN) T cells. This was shown by FACS analysis as this putative pathogenic population was diminished in both spleen and lymph node. The symptoms of systemic lupus erythematosus (SLE) in MRL/lpr, which include high titers of anti-DNA antibodies and circulating immune complexes and proteinuria, were reduced in SEB-treated mice in a dose-dependent manner. The clinical parameters of SLE in MRL/lpr, which include lymph node hyperplasia and necrotic vasculitis, were suppressed in 50-micrograms SEB-treated mice. T cells bearing V beta 6 T cell receptor, which does not interact with SEB, were not reduced with SEB administration. Thus, disease suppression was associated with a specific reduction in the number of V beta 8+, DN T cells. These results implicate a possible therapeutic role of superantigen-based immunotherapy in V beta-restricted, T cell-dominated clinical syndromes. PMID- 1744581 TI - Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I. AB - 14 gorilla class I major histocompatibility complex (MHC) alleles have been isolated, sequenced, and compared to their counterparts in humans and chimpanzees. Gorilla homologues of HLA-A, -B, and -C were readily identified, and four Gogo-A, four Gogo-B, and five Gogo-C alleles were defined. In addition, an unusual Gogo class I gene with features in common with HLA-A and its related pseudogene, HLA-H, is described. None of the gorilla alleles is identical or even closely related to known class I alleles and each encodes a unique antigen recognition site. However, the majority of polymorphic substitutions and sequence motifs of gorilla class I alleles are shared with the human or chimpanzee systems. In particular, elements shared with HLA-A2 and HLA-B27 are found in Gogo A and -B alleles. Diversity at the Gogo-B locus is less than at the Gogo-A locus, a trend the opposite of that seen for HLA-A and -B. The Gogo-C locus also appears to have limited polymorphism compared to Gogo-A. Two basic Gogo-C motifs were found and they segregate with distinctive sets of HLA-C alleles. HLA-A allels are divided into five families derived from two ancient lineages. All chimpanzee A alleles derived from one of these lineages and all gorilla alleles derive from the other. Unlike chimpanzee Patr-A alleles, the Gogo-A alleles do not clearly partition with one of the HLA-A families but have similarities with two. Overall, gorilla class I diversity appears from this sampling to show more distinctions from class I HLA than found for chimpanzee class I. PMID- 1744582 TI - Interleukin 7 generates antitumor cytotoxic T lymphocytes against murine sarcomas with efficacy in cellular adoptive immunotherapy. AB - Interleukin 7 (IL-7) is a 25-kD cytokine that was initially described as a pre-B cell growth factor. This cytokine has also been shown to have T cell proliferative and differentiation effects. In this report, we demonstrate that antitumor cytotoxic T lymphocytes (CTL) generated by secondary in vitro sensitization of draining lymph node cells in IL-7 are effective in treating 3 day syngeneic methylcholanthrene (MCA) sarcoma pulmonary metastases in mice. In vivo titrations comparing IL-7 to IL-2 antitumor CTL show that they have equivalent potency in adoptive immunotherapy. IL-7 antitumor CTL generated against MCA sarcomas of weak immunogeneity are also tumor specific in their in vivo efficacy. This study represents the first successful use of a cytokine other than IL-2 for the generation of cells with in vivo efficacy in cellular adoptive transfer. PMID- 1744583 TI - Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. AB - Lipopolysaccharide (LPS) activation of cells of monocytic lineage leads to rapid and transient expression of a set of inflammatory gene products, including tissue factor (TF). This transmembrane receptor is the major cellular initiator of the blood coagulation cascades, and induced expression of TF is postulated to play a role in inflammation. Functional studies using transfected THP-1 monocytic cells revealed the presence of a 56-bp LPS response element (LRE) within the TF promoter that conferred LPS responsiveness to a heterologous promoter. LPS stimulation of these cells activated proteins that bound to nucleotide sequences within the LRE resembling consensus binding sites for activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B). Induction of the TF gene may represent a prototypic example of gene activation in monocytic cells by assembly of transcription factor complexes, and may clarify the role of AP-1 and NF-kappa B in the regulation of other LPS-responsive genes. PMID- 1744584 TI - Macrophage deactivation by interleukin 10. AB - Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL 10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently. PMID- 1744585 TI - A novel beta 4, alpha 6 integrin-associated epithelial cell antigen involved in natural killer cell and antigen-specific cytotoxic T lymphocyte cytotoxicity. AB - Efficient immune responses require interactions between cell adhesion molecules on lymphocytes and counter-receptors on antigen presenting cells or target cells. While target-specific receptors or ligands have not been identified for natural killer (NK) cells, cell adhesion molecules have been implicated in the interaction between NK cell effectors and tumor cell targets. Herein, we describe monoclonal antibodies (mAbs) against a carcinoma cell line that efficiently block the cytolytic activity of interleukin 2-activated NK cell lines and clones. L280 mAb reacts with secretory epithelial cells in normal human tissues, but does not react with hematopoietic cells or other tissue types. Biochemical analysis revealed that L280 mAb immunoprecipitates the beta 4, alpha 6 integrin, as well as a novel 98-kD glycoprotein, and probably reacts with a carbohydrate epitope on these molecules. Involvement of the L280 antigen in cellular immunity is not restricted to NK cell-mediated cytotoxicity. L280 mAb also efficiently inhibits alloantigen-specific cytotoxicity against Colo-205 cells mediated by human histocompatibility leukocyte antigen (HLA)-A2 alloantigen specific alpha beta TCR+ and gamma delta-TCR+ cytotoxic T lymphocyte (CTL) clones. Additionally, we demonstrate that L280 mAb blocks cytotoxicity mediated by influenza peptide specific HLA-restricted CTL clones. These data indicate that the antigen recognized by L280 mAb is important in both NK and CTL function, and that an as yet unidentified receptor for this epithelial antigen is present on both NK and T lymphocytes. The restricted expression of L280 antigen indicates that this molecule may be important in immune reactions in epithelial tissues. PMID- 1744586 TI - Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities. AB - The presence of cytotoxic T lymphocytes (CTL) to the gag antigens of human immunodeficiency virus (HIV) has been described in infected populations. We found that the majority of this immune response as measured in bulk CTL assays of unstimulated peripheral blood mononuclear cells (PBMC) is directed against the p24 component of the p55 gag precursor protein. Using limiting dilution analysis of this effector cell population we confirm that the majority of activated gag specific CTL circulating in the PBMC of infected hemophilic patients are directed at p24 determinants and are present at frequencies of 1/36,000 to 1/86,000 lymphocytes. By performing in vitro stimulation after limiting dilution, the precursor population of gag-specific CTL are characterized and quantitated. HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities. No HIV gag-specific CTL precursor cells are identified in the PBMC of HIV-uninfected individuals. These studies demonstrate that CTL directed at both p17 and p24 determinants make up the cellular immune repertoire in HIV-infected individuals but that only the p24-specific CTL are routinely found in an activated state in the circulation. PMID- 1744587 TI - Expression of paragloboside-like lipooligosaccharides may be a necessary component of gonococcal pathogenesis in men. AB - To learn how lipooligosaccharide (LOS) phase variations affect pathogenesis, we studied two male volunteers who were challenged intraurethrally with Neisseria gonorrhoeae that make a single LOS of 3,600 daltons and sequentially followed LOS expression by gonococci as urethritis developed. LOS variation occurred in vivo. Signs and symptoms of gonorrhea began with the appearance of variants making 4,700-dalton LOS that are immunochemically similar to glycosphingolipids of human hematopoietic cells (Mandrell, R.E., J.M. Griffiss, and B.A. Macher. 1989. J. Exp. Med. 168:107) and that have acceptors for sialic acid. A variant that appeared at the onset of leukorrhoea was shed by 34/36 men with naturally acquired gonorrhea at the time they sought medical attention; the other two shed the variant associated with dysuria. None shed the challenge variant. These data show that in vivo phase shifts to higher molecular mass LOS that mimic human cell membrane glycolipids are associated with the development of gonococcal leukorrhea. PMID- 1744588 TI - A gene required for class II-restricted antigen presentation maps to the major histocompatibility complex. AB - We have previously described a set of mutants (16.23-selected mutants) of a B lymphoblastoid cell line that are defective in the presentation of intact proteins to class II-restricted T cells, but effectively present immunogenic peptides. The mutations in these mutants are recessive in somatic cell hybrids and are not in Class II structural genes. Here, we report on a unique mutant, 5.2.4, in which a similar defect in class II-restricted antigen presentation has occurred in association with a one-megabase homozygous deletion in the class II region of the major histocompatibility complex (MHC). The defects in class II presentation among three of the 16.23-selected mutants, and between these mutants and 5.2.4, are noncomplementary in somatic cell hybrids. This suggests that the class II presentation-defective phenotype in all four mutants results from lesions in a single MHC-linked gene, a conclusion strengthened by the finding that in a hybrid made with a second, unrelated MHC deletion mutant, T2, the class II presentation defect in a 16.23-selected mutant is also not complemented. Mutant 5.2.4, in addition to its class II presentation defect, is also defective in surface expression of MHC class I molecules, most likely because its deletion encompasses the peptide supply factor 1 gene, whose function is known to be required for normal abundance of cell surface class I molecules. However, the surface abundance of class I molecules is normal in the 16.23-selected mutants, suggesting that the lesions affecting class I surface abundance and class II presentation result from mutations in different genes. PMID- 1744589 TI - Strong priming of T cells adoptively transferred into scid mice. AB - We have examined the requirements for activating unprimed T cells in vivo by transferring T cells into scid mice, which lack mature B and T cells. Purified adult thymocytes and a protein antigen, keyhole limpet hemocyanin (KLH), were injected into scid mice. scid mice injected with T cells and KLH developed cellular lymph nodes containing CD4+ and CD8+ T cells. Cells recovered from the lymph nodes of injected scid mice proliferated and secreted interleukin 2 in response to KLH in vitro. The results indicate that T cells can be primed to KLH in the scid mouse in the absence of B cells. PMID- 1744590 TI - Conversion of a self peptide sequence into a Kd-restricted neo-antigen by a Tyr substitution. AB - We have previously found that a Tyr residue was critical for the interaction of peptides with the Kd molecule, and therefore may be acting as an anchor residue. In the present report we show that it is possible to convert a self peptide sequence into a Kd-restricted neo-antigen by a single Tyr substitution at position 2 of the peptide. This supports the idea that Tyr is a critical element in the binding motif of Kd-restricted peptides and is a finding that could also prove useful for vaccine development. PMID- 1744591 TI - Human immunodeficiency virus infection of eosinophils in human bone marrow cultures. AB - Normal human bone marrow, cultured in vitro with interleukin 5 to promote eosinophil production and maturation, was inoculated with cell-free isolates of human immunodeficiency virus type 1 (HIV-1). CD4 expression by eosinophil precursors, determined by immunocytochemistry, was found to be greatest early in their maturation with a rapid decline after 28 d in culture. Productive HIV infection of eosinophil precursors was detected 14 d after inoculation, by a combination of immunostaining for HIV-1 p24 and gp41/160 and in situ hybridization for viral RNA, together with assay of culture supernatants for p24 antigen and reverse transcriptase activity. Thus, eosinophils are susceptible to productive HIV-1 infection in vitro and may be an important reservoir for the virus in vivo. PMID- 1744592 TI - Fine specificity of cytotoxic T lymphocytes primed in vivo either with virus or synthetic lipopeptide vaccine or primed in vitro with peptide. AB - Standard synthetic peptide preparations contain numerous peptidic byproducts in small amounts, which may be efficiently recognized by cytotoxic T lymphocytes (CTL). Recognition patterns of such peptide mixtures by CTL may serve as a kind of fingerprint for CTL fine specificity. Three types of H-2Db-restricted CTL were compared in this way. CTL primed in vivo either with A/PR/8/34 influenza virus or with a synthetic lipopeptide vaccine prepared from influenza nucleoprotein (NP) peptide 365-380 showed identical fine specificity. Both recognize virus-infected cells. In contrast, CTL primed in vitro with NP 365-380 had a different fine specificity and they did not recognize virus-infected cells. Most significantly, the two in vivo primed CTL types efficiently recognized the natural viral nonapeptide NP 366-374 presented by virus-infected H-2b cells, whereas the in vitro primed CTL failed to do so. PMID- 1744593 TI - Species differences in spatial memory among Clark's nutcrackers, scrub jays, and pigeons. AB - An operant nonmatching to sample procedure was used to compare the spatial memory abilities of 3 avian species. A trial consisted of the presentation of a spatially defined sample, a delay interval, and a 2-choice test during which the correct location was the new location. A single spatial location served as the sample in Experiment 1. The delay interval was manipulated using a titration procedure. In Experiment 2, 1, 2, or 3 sequentially illuminated locations served as the sample. The delay was 1 of 4 predetermined intervals. In Experiment 3, sample presentation was the same as Experiment 2, but the delay interval was titrated. In all of the experiments, the performance of nutcrackers was consistently better than the performance of scrub jays and pigeons (Experiment 1) and was correlated with differences in their foraging ecology. PMID- 1744594 TI - Echoic memory in the rat: effects of inspection time, retention interval, and the spectral composition of masking noise. AB - Memory for tones (1100 vs. 2330 Hz) was studied in 4 rats (Rattus norvegicus), as affected by the durations of both target tones (30 to 620 ms) and noise-filled retention intervals (0 to 480 ms). With a 0-ms delay, performance was near asymptotic with the 30-ms tone, but the memory of this brief tone suffered a massive decrement at retention intervals as brief as 60 ms; in contrast, memory for the 340-ms tone was stable for at least 240 ms. If the retention interval was filled by band-stop noise (with targets presented in the spectral gap), then the rat's memory for brief tones was superior to that obtained with the standard broad-band noise filler, and band-stop noise was better than a band-pass noise that had the tones embedded in the region of its spectral energy. These findings are consistent with the hypotheses that auditory memory in the rat consists of a transient sensorylike echoic store and a short-term store more resistant to the effects of retroactive interference. PMID- 1744595 TI - Serial learning by rhesus monkeys: I. Acquisition and retention of multiple four item lists. AB - Two rhesus monkeys were trained to learn eight 4-item lists, each composed of 4 different photographs. Lists were trained in successive phases: A, A----B, A----B ---C, and A----B----C----D. After List 4, retention, as measured by the method of savings, was, on average, 66% (range: 44-84%). Indeed, all 4 lists could be recalled reliably during a single session with neither a decrement in accuracy nor an increase in the latency of responding to each item. Response latencies on a subset test employing all possible 2- and 3-item subsets of each 4-item list support the hypothesis that monkeys form linear representations of a list. Latencies to Item 1 of a subset varied directly with the position of that item in the original list. On List 1, latencies to Item 2 varied directly with the number of intervening items between Item 1 and Item 2 in the original list. During the acquisition of Lists 5-8, both Ss mastered the A----B and A----B----C phases of training in the minimum number of trials possible. PMID- 1744596 TI - Conditioning of the rabbit's nictitating membrane response to a CSA-CSB-US serial compound: manipulations of CSB's associative character. AB - Response acquisition to a trace conditioned stimulus (CSA) can be facilitated by insertion of a second stimulus (CSB) at the end of the trace interval just before the unconditioned stimulus (US). This effect may arise from serial mediation of trace conditioning, second-order conditioning, or both. Whereas serial mediation relies only on the presence of CSB, associative transfer relies on CSB's associative strength. In the present experiments, the presence of CSB was fixed, whereas CSB's associative strength was manipulated by (a) extinction of CSB, (b) latent inhibition of CSB, and (c) prior CSB-US pairings. In the first 2 cases, the level of responding to CSA was reduced in a fashion parallel to that of CSB. However, in the third case, partial blocking of conditioned response (CR) acquisition to CSA was observed. The results are discussed with reference to the role of associative transfer to both facilitating and blocking CR acquisition to CSA. PMID- 1744597 TI - Establishing intermodal equivalence in preweanling and adult rats. AB - Interactions between olfactory and brightness conditioning were examined in infant (16-day-old) and adult rats. Conditioning to an odor (methyl salicylate [MS] paired with footshock [FS]) was followed by subthreshold conditioning to an unscented black box (paired with FS). Controls were given unpaired presentations in either the 1st or the 2nd phase of this treatment. No age-related differences in conditioning occurred when either phase was presented alone. Significant aversion to the black box was observed after the experimental treatment only in infants, and brightness conditioning potentiated odor conditioning in infants but not adults. In the infants, odor-extinction procedures weakened the aversion to the black box as well as to MS. Olfactory-to-visual transfer required that the same unconditioned stimulus be paired with both conditioned stimuli. These results may reflect an infantile disposition for unitization. PMID- 1744598 TI - Development of intersensory function: age-related differences in stimulus selection of multimodal compounds in rats as revealed by Pavlovian conditioning. AB - Preweanling and adult rats were exposed to Pavlovian stimulus pairings with lights, tones, and light-tone compounds as conditional stimuli (CSs). Tone intensity was varied. As was found in previous studies using flavor CSs, odor CSs, or both, in which significant overshadowing or potentiation occurred to an element of a compound, overshadowing was less likely and potentiation more likely for preweanlings than for adults. Several experiments supported the view that these effects reflect an age-related difference in the controlling properties of stimuli: Young rats are more disposed to encode multimodal compounds on the basis of amodal intensity, whereas their elders are more likely to encode modality specific properties of light and sound. Differential reinforcement in the presence of lights, tones, and light-tone compounds made preweanlings' stimulus selection appear more adultlike and may be a cause of development of intersensory function. PMID- 1744599 TI - Diabetes screening. PMID- 1744600 TI - Efficient diagnosis. PMID- 1744601 TI - Vasectomy: principles and comments. PMID- 1744602 TI - Sports medicine: the times, they are a-changin'. PMID- 1744603 TI - Complications in a series of 1224 vasectomies. AB - BACKGROUND: The assessment of a vasectomy technique should be based on the incidence of complications resulting from the procedure. Differing diagnostic criteria for defining complications and the belated occurrence of some adverse events, however, have made such appraisals difficult. The purpose of this paper is to suggest criteria for defining vasectomy-related problems and to present the results of a long-term study of 1224 vasectomies. METHODS: The records of 1224 men who had a vasectomy performed by the same technique during a 4-year period were reviewed, and documented complications were tabulated and evaluated. Patients were referred residents of the lower mainland of British Columbia, and the majority were married. The group included a wide spectrum of ages, races, and occupations. Twelve categories of potential complications were defined, of which 10 were actually encountered in the study group. Infection was defined as having had antimicrobial drugs prescribed, and regret as having returned to discuss a reversal; all other complications were diagnosed based on a documented clinical diagnosis. RESULTS: Complications had been documented in 124 cases (10.6%) and included 46 minor infections (3.8%), 2 serious infections (0.16%), 23 instances of epididymitis (1.9%), 16 cases of sperm granuloma (1.3%), and 4 minor hemorrhages (0.33%). Of 3 failures, only one (0.08%) was due to recanalization. No serious hemorrhages or late failures were seen. CONCLUSIONS: Satisfactory results were believed to be related to surgical technique and the liberal use of antimicrobial drugs. The low recanalization rate was attributed to the treatment of the ends of the vas with multiple loops of polyglycolic acid ligature. PMID- 1744604 TI - Lifestyles and health risks of collegiate athletes. AB - BACKGROUND: No study has comprehensively assessed the health behaviors of intercollegiate athletes. To determine whether they may be at increased risk for unhealthy lifestyle behaviors, we compared the lifestyle and health risk behaviors of a group of college athletes with those of their nonathletic peers. METHODS: A confidential survey questionnaire addressing preventable lifestyle behaviors was given to 109 intercollegiate athletes and 110 nonathlete controls. RESULTS: Athletes had a significantly (P less than .05) higher proportion of "risky" lifestyle behavior patterns compared with the nonathletes in the following areas: quantity of alcohol consumed; driving while intoxicated with alcohol or other drugs; riding with an intoxicated driver; use of seatbelts; use of helmets when riding a motorcycle or moped; use of contraception; number of sexually transmitted diseases; and number of sexual partners. CONCLUSIONS: College athletes appear to be at higher risk for certain maladaptive lifestyle behaviors. Comprehensive lifestyle assessment and preventive health intervention deserve further study to determine whether they can facilitate the adoption of positive lifestyle behaviors in this high-risk group. PMID- 1744605 TI - Accuracy of patient encounter and billing information in ambulatory care. AB - BACKGROUND: This study examined the degree of accuracy of billing data in an academically affiliated family practice. METHODS: The progress notes from 1253 consecutive visits were independently reviewed by two family physicians, and the diagnoses, use of procedures, and level of service were determined for each visit. Discrepancies between the reviewers were resolved by consensus. These data were compared with the data on the corresponding billing form that had been completed by the care providers (ie, physicians on the faculty, physicians in training, family nurse practitioners, and nurses). RESULTS: There was poor agreement between the billing form and progress note on level of service and number of diagnoses (kappa = 0.37 and kappa = 0.28, respectively). The progress note usually indicated that a higher level of service should have been billed for a visit than actually was billed. Underreporting of the number of diagnoses was substantial; the billing forms listed only 69% of the diagnoses identified in the progress notes. In 60% of visits, each diagnosis on the billing form had a matching diagnosis in the progress note. This could be improved to 78% of visits if broad categories of disease were used. Residents were similar to faculty in the accuracy of reported level of service and types of diagnoses, but were more likely to underreport the number of diagnoses. CONCLUSIONS: Ambulatory care data from computerized billing files may not be sufficiently accurate for proper reimbursement of physician services or for use in research. PMID- 1744606 TI - Relationship of infant mortality to the availability of obstetrical care in Indiana. AB - BACKGROUND: Projects that are currently under way in Indiana to improve access to obstetrical care have not addressed the availability of these services in nonmetropolitan areas. This study was designed to identify all physicians who were providing obstetrical services in every county throughout the state to determine if there is a correlation between the availability of these services and the infant mortality rate in nonmetropolitan counties. METHODS: A state-wide physician profile maintained by the Indiana Academy of Family Physicians was cross-referenced with a telephone survey of all hospitals in the state to identify those physicians providing obstetrical services within each county in Indiana. The number of physicians in each county was then compared with the number of births per year by mothers from that county to determine whether nonmetropolitan counties had sufficient physicians to provide obstetrical services. Finally, these findings were compared with the most recent infant mortality rate for each nonmetropolitan county. RESULTS: A total of 610 family physicians, 311 obstetricians, and 75 general practitioners were providing obstetrical care in Indiana. There were 10 counties that did not have a physician who delivered babies practicing in that county. Thirty-two counties had more women who needed obstetrical care than the current number of physicians could serve. There was a negative correlation between physician availability and infant mortality in Indiana's nonmetropolitan counties (r = -.38; P less than .02). CONCLUSIONS: Access to care for pregnant patients is a major problem in rural Indiana and hampers Indiana's ability to reduce its current infant mortality rate. PMID- 1744607 TI - 'White coat' hypertension in children. AB - BACKGROUND: Research with ambulatory blood pressure monitoring (ABPM) clearly demonstrates the importance of identifying "white coat" hypertension before making the diagnosis of hypertension. While the existence of white coat hypertension has been documented in adults, it is unknown whether this phenomenon is present during childhood. Therefore, the purposes of this study were to determine whether white coat hypertension exists in children with a positive family history of essential hypertension; and if it exists, to compare 24-hour ambulatory blood pressure patterns among normotensive, white coat hypertensive, and hypertensive children. METHODS: One hundred fifty-nine children (aged 5 to 15 years) participated in the study. Based on office systolic and diastolic measurements and 24-hour ABPM, subjects were placed into one of three groups: normotensive, white coat hypertensive, and hypertensive. RESULTS: Forty-four percent of 34 subjects with systolic blood pressures greater than or equal to 95th percentile were reclassified as white coat hypertensive; 56% remained hypertensive. Group comparisons of 24-hour ABPM patterns showed significant differences between groups. Also, the ABPM patterns of white coat hypertensive patients were significantly different from those of normotensive patients. CONCLUSIONS: This study documented the existence of white coat hypertension in children and showed that white coat hypertensive children were significantly different from normotensive and hypertensive children on most comparisons of 24 hour ABPM data. Also, when age and sex were controlled, heavier children had a more significant chance of having elevated systolic blood pressure than normal weight children, regardless of their race, height, or body mass index. PMID- 1744608 TI - Colpophotography systems: a review. AB - Colpophotography and video colposcopy systems are useful for pathology documentation purposes, patient education, and colposcopy training. A wide variety of colposcopic visual media components are available to enhance routine colposcopy. Colpophotographic systems supplied by eight colposcope manufacturers were critically evaluated by a colposcopist and a medical photographer. Components were independently and objectively analyzed. Photographic examination considered color, illumination uniformity, and coverage of illumination at all possible colposcopic magnifications. Photographs were developed by a standardized technique. The investigation results clearly demonstrated variability between different colpophotographic systems. Quality colpophotography is dependent on certain colposcope features and potential modifications. Colpophotography and video colposcopy systems complement the standard colposcopic procedure. PMID- 1744609 TI - Superficial thrombophlebitis of the anterior chest wall (Mondor's disease). PMID- 1744610 TI - Foley catheter retention: a case report. PMID- 1744611 TI - US Preventive Services Task Force: an update on current activities. PMID- 1744612 TI - Morphological basis of "growling" in the king cobra, Ophiophagus hannah. AB - A bioacoustic analysis is conducted on the defensive sounds produced by 21 species of snakes. The "typical" snake hiss is described as having a broad frequency span (from roughly 3,000 to 13,000 Hertz) and a dominant frequency near 7,500 Hertz. The "growl" of the king cobra (Ophiophagus hannah) differs from the "typical" snake hiss in consisting solely of frequencies below 2,500 Hertz, with a dominant frequency near 600 Hertz. Structural analysis of the upper respiratory tract of O. hannah suggests that the "growl" is produced by tracheal diverticula functioning as low-frequency resonating chambers. This hypothesis is supported in several ways. An acoustic analysis of a mechanical model of the trachea demonstrates the potential for these diverticula to produce resonance effects. A "growl" also occurs in the mangrove ratsnake (Gonyosoma oxycephalum), a species that also has tracheal diverticula. Flushing the respiratory tract of G. oxycephalum with helium produces a shift of over 1,000 Hertz in the "growl," a shift that is indicative of a resonance effect. PMID- 1744613 TI - Chemical repellency in birds: relationship between chemical structure and avoidance response. AB - We examined how molecular structure of 24 anthranilate and benzoic acid derivatives correlated with drinking behavior in European starlings Sturnus vulgaris. The effectiveness of bird repellents was associated with basicity, the presence of an electron-donating group in resonance with an electron-withdrawing carboxylic group on a phenyl ring, and a heterocyclic ring in the same pi cloud plane as the phenyl ring. Of the benzoic acid derivatives tested in this study, methyl, ethyl, dimethyl, and linalyl anthranilate as well as anthranilic acid and 4-ketobenztriazine were repellent to birds. Water consumption was significantly reduced relative to control levels at concentrations as low as 0.05% (weight/volume) for the best repellents. Further statistical tests showed that reduction in consumption for the best repellents was absolute, not significantly different from zero consumption. Anthranilic acid isomers were moderately good repellents. The ability to generate a model predicting repellency allows for the efficient identification and development of ecologically sound, nonlethal, taxa specific repellents to be used for the protection of wildlife in agricultural and industrial applications. PMID- 1744614 TI - The effects of orchidectomy and gonadotropins on steroidogenesis and oogenesis in Bidder's organs of the toad Bufo woodhousii. AB - In the family Bufonidae, male toads possess rudimentary ovaries, called Bidder's organs, which are attached to the testes. The mechanisms involved in the inhibition of oogenesis in these structures were investigated in male Bufo woodhousii. Orchidectomized and sham-operated animals were injected with gonadotropins (pregnant mare serum gonadotropin [PMSG] + human chorionic gonadotropin [hCG]) for 26 days and the effects of these hormones on oogenesis and steroidogenic activity (3 beta-hydroxysteroid dehydrogenase [3 beta-HSD] and 17 beta-HSD) in the Bidder's organ were quantified. Bilateral orchidectomy alone resulted in the growth of bidderian oocytes and a shift towards later stages of oogenesis. Gonadotropins enhanced this effect and stimulated the proliferation of new germ cells. In the presence of testes, however, bidderian oogenesis remained inhibited despite high levels of circulating gonadotropins. In both ooplasm and follicular layers of the bidderian oocytes of all toads, 3 beta-HSD and 17 beta HSD activities were detected by histochemistry. Follicular enzymatic activity increased in orchidectomized toads treated with PMSG + hCG but decreased in sham operated toads treated with gonadotropins. Testis weights, rudimentary oviduct weights, and plasma steroid levels increased in intact toads injected with hCG + PMSG. Gonadotropins had no effect on plasma steroid levels in orchidectomized toads, however. These results suggest that the testes play a major role in the inhibition of oogenesis in Bidder's organs of B. woodhousii and are a major source of androgens. High circulating levels of gonadotropins do not overcome the inhibitory effects of the testes. PMID- 1744615 TI - The behavior and cytoskeletal system of chick gastrula mesodermal cells on substrata coated with lines of fibronectin. AB - In order to investigate the mechanism of the formation of the mesodermal layer during chick gastrulation, we observed the behavior of fragments of mesodermal cells explanted and cultured on substrata coated with parallel lines of fibronectin (FN). We also examined the distribution of F-actin, alpha-actinin, and vinculin in explanted fragments by immunocytochemical methods noting particularly their distribution with respect to FN lines. Explants of mesodermal cells flattened on FN-coated substrata and then became elliptical with the major axis of the ellipse oriented along the FN lines and migrated along them. The peripheral cells of explants extended filopodia and lamellipodia which attached preferentially to FN lines and then contracted, pulling other mesodermal cells in explants along passively. Vinculin and alpha-actinin in peripheral anchoring filopodia and lamellipodia co-localized with the terminations of F-actin bundles and with FN lines, suggesting that the peripheral cells were the moving force for explant translocation. We propose based on these results that in vivo, peripheral cells of invaginated cell mass are guided by the known FN-rich fibrous extracellular matrix on the basal surface of epiblast to move outwards; the rest linked to the peripheral cells are pulled away from the primitive streak to spread in tandem to form the mesodermal layer. PMID- 1744616 TI - Early innervation of skeletal muscle during tail regeneration in urodele amphibians. AB - The innervation pattern of skeletal muscles was studied in the normal and regenerating tail of Notophthalmus viridescens. Silver staining for nerve endings and histochemical localization of acetylcholinesterase (AChE) were used for light microscopy. In In normal musculature, AChE positive reactions were localized at the ends of the muscle fibers where they are anchored on connective tissue septa by myotendinous junctions. At this level, silver staining shows nerve terminals forming endplates. During regeneration, positive reactions for AChE appear de novo as dense plates localized at the ends of the newly formed myotubes. The mechanisms involved in the localization of AChE on this surface seem to operate before previous local contacts by nerve terminals. From the ultrastructural data and immunohistochemical results with anti-laminin antibody, these observations suggest that regenerating muscle fibers determine a region of post-synaptic specialization in close relation with the organization of myotendinous regions and basement membrane formation. Nerve-muscle contacts appear at these levels at stage IV (15-20 days after amputation) in the stump and in the rostral part of the regenerate (transition zone). These nerve terminals are provided by the disorganized peripheral nervous system of the injured segment. In the regenerate a similar pattern of AChE reaction can be seen in every myotube, differentiating according to a rostro-caudal gradient. Innervation at the ends of the muscle fibers is in spatiotemporal relation with the exists of the ventral roots from the regenerating nerve cord as the regenerate continues to grow in length. PMID- 1744617 TI - Chronology and morphology of temperature-dependent sex determination. AB - Temperature sensitivity and gonadal differentiation were studied in a turtle, Trachemys scripta, with temperature-dependent sex determination. Sex determination was sensitive to both the duration and magnitude of incubation temperature. Temperature exerted an "all or none" effect on the ovarian or testicular nature of most gonads, but affected the length of ovaries in a graded fashion. Collectively, the results indicate that sex determination is controlled by the quantitative effect of temperature during a period beginning prior to (histologically detectable) sexual differentiation and extending to a time when initial sex specific changes are evident in the gonads. PMID- 1744618 TI - Genetic analysis of androgenetic rainbow trout. AB - We analyzed a number of genetic characteristics in androgenetic rainbow trout (Oncorhynchus mykiss) and their progeny. The androgenetic progeny of individual androgenetic males appeared genetically identical to each other based on eight enzyme loci. Their viability was no higher than that of androgenetic progeny of outbred males. Homozygous androgenetic female rainbow trout produced very poor quality eggs. When common eggs and sperm from outbred individuals were used to produce androgenetic and gynogenetic progeny, the yield of gynogenetic progeny was higher but some were heterozygous at protein loci, while no androgenetic progeny were heterozygous. Some androgenetic diploid rainbow trout were successfully produced from cryopreserved sperm. The progeny of some androgenetic males crossed to normal females were virtually all males, while the progeny of other males were virtually all females. This suggests that both XX and YY androgenetic individuals may develop as males. Androgenesis is likely to be useful for generating homozygous clones for research and for recovering strains from cryopreserved sperm. PMID- 1744619 TI - Proliferation of lymphocyte-like cells from the solitary tunicate, Styela clava, in response to allogeneic stimuli. AB - Lymphocyte-like hemocytes (LLCs) of solitary tunicates proliferate in response to allogeneic stimuli. In vitro labeling of proliferative hemocytes from the solitary species Styela clava revealed significantly greater proliferative activity among individuals immunized with allogeneic tissue as opposed to autogeneically primed and naive animals. Enhanced proliferation was restricted to discrete crypts of dividing cells within the body wall of recipients. Here, increased proliferative activity was specifically associated with LLCs. These data support previous results which implicated LLC activity with immunological memory that is evident in allograft rejection. Hence, it is postulated that adaptive histoincompatibility responses in solitary tunicates depend upon the specific proliferation of immunocompetent cells. PMID- 1744620 TI - An increase of intracellular free Ca2+ is essential for spontaneous meiotic resumption by mouse oocytes. AB - The involvement of calcium ions in the mechanism of meiotic resumption has been studied in mouse oocytes made resistant to the lethal effects of calcium-free medium (CFM) by zona pellucida removal (De Felici et al., '89). We show here that such oocytes undergo meiotic resumption in CFM (as evaluated by germinal vesicle breakdown, GVBD) at a rate comparable to that shown by oocytes cultured in medium containing 1.7 mM Ca2+. The addition to CFM of 50 u M Quin2/AM (a membrane permeable, high affinity Ca2+ chelator) totally prevents GVBD, while purported antagonists of Ca2+ release from intracellular stores, such as 150 uM 8-(N,N diethylamino)octyl-3-4-5 trimethoxybenzoate (TMB-8) or 300 uM chlortetracycline, only cause a slight meiotic delay. On the other hand, if the oocytes are pre incubated for 30 min in CFM supplemented with 100 uM TBM-8 plus 0.2 mM dibutyryl cyclic AMP (dbcAMP, a reversible inhibitor of GVBD), and then cultured in the same medium, without dbcAMP, a sustained inhibition of meiotic maturation is obtained. Our observations suggest that an increase in intracellular free Ca2+ is essential for meiotic resumption by mouse oocytes; in the experimental absence of external Ca2+, release of the cation from internal stores is sufficient to allow meiotic resumption. PMID- 1744621 TI - At least half of capacitated, motile mouse sperm can fertilize zona-free mouse oocytes. AB - The percentage of individual sperm capable of fertilizing zona pellucida-free mouse oocytes was investigated by placing motile sperm near zona-free oocytes with a micromanipulator. Incubation with one or two capacitated sperm per oocyte resulted in 50% and 70% fertilization, respectively, compared to 88% for cumulus intact (10(5) sperm/ml) and 87% for zona-free (2 x 10(3) sperm/ml) control oocytes. When sperm were treated with .1 microM calcium ionophore A23187 to facilitate the acrosome reaction, fertilization rates for single motile sperm were markedly lower than for capacitated, nontreated single sperm (4% and 35%, respectively). Similar fertilization rates resulted when one sperm was incubated per two ova (4% and 48% per sperm for A23187-treated and controls, respectively). When a lower dose of A23187 (.001 microM) was used to treat sperm, 7% of oocytes incubated with single sperm were fertilized. These experiments demonstrate that at least half of motile, capacitated mouse sperm are capable of fertilizing zona free mouse oocytes in vitro, and that motile, A23187-treated mouse sperm resulted in poor fertilization rates. PMID- 1744622 TI - The detection of aerosol propellants in body fluids and tissue by gas chromatography-mass spectrometry. AB - The increased incidence of aerosol abuse in recent years has led to the development of a method for the detection of halogenated hydrocarbons in body fluids and tissue compatible with other routine methods. The use of the method in two background studies and a case investigation is described. PMID- 1744623 TI - A simple method for collection of gunshot residues from clothing. AB - Simple equipment for the sampling of gunshot residue particles from clothing, inside of bags, pockets, etc, is described. Collection was achieved by vacuuming through a double filtration system constructed from a Nucleopore aerosol holder connected to an ordinary vacuum cleaner. The collected particles were examined by scanning electron microscopy. Good results were observed in functional tests of this equipment and the method has been introduced into casework in our laboratory. Various experiments on possible contamination of clothing by GSR particles were performed. The usefulness of clothing as evidence material in searching for GSR particles is discussed. PMID- 1744624 TI - Eliminating ill-founded eliminations in handwriting comparison cases. AB - Document examiners sometimes eliminate writers on the basis of differences which are given too much weight. This article is an attempt to explain some conditions whereby differences in the writing of one individual are misinterpreted as significant differences, when they are actually caused by conditions which are unknown to the examiner. PMID- 1744625 TI - The analysis of clingfilms by infrared spectroscopy and thermal desorption capillary gas chromatography. AB - An automated thermal desorption gas chromatography technique has been adapted to analyse traces of volatile compounds in proprietary food-wrapping films. Fourteen brands of polyvinylchloride film, seven brands of polyethylene film and one polyvinylidene chloride film were discriminated. Prior infrared analysis was used to identify the polymer type. The chromatograms showed minor changes in volatiles along the length of a roll of film and major changes in films exposed to daylight or in contact with cannabis resin. PMID- 1744626 TI - The attribution of blame and type of crime committed: transcultural validation. AB - This study examines the relationship between type of offence and the attributions offenders make about their criminal act. The subjects were 98 Icelandic criminals who had completed the Gudjonsson Blame Attribution Inventory. Significant differences in attribution were found between offender groups. Sex offenders and those who had committed acts of interpersonal violence reported most guilt about their offence and they attributed cause for their offence more to mental factors (eg, loss of self-control) than other types of offender. Violent offenders had the highest external attribution and sex offenders the lowest. The findings with regard to the three attributions are remarkably similar to those found previously for British offenders. PMID- 1744627 TI - A continuous model for interpreting the positions of bands in DNA locus-specific work. AB - A simple but rigorous approach is offered for evaluating the evidential value of single locus DNA autoradiographs. This approach does not use a binning technique and it does not treat alleles as discrete variables. Instead, the allele distribution is considered to be continuous. The variation between two comparable bands is assessed using previously determined experimental parameters. The Bayesian treatment leads to an expression of the "quality of a match". PMID- 1744628 TI - Decision making in clinically depressed patients. A transcultural social psychological study. AB - One of the most important cognitive deficits in depression is said to be the patient's inability to make decisions. A research design involving a cross cultural comparison between Australian and Japanese normal controls (N = 309 and N = 743, respectively) and clinically depressed patients (N = 59 and N = 45, respectively) was used to examine the influence of culture on illness and decision-making behavior, and whether deficits in decision making may be related to culture. It was found that depression had a greater effect on decision making in Australian patients than in Japanese patients. While many differences were found between Australian and Japanese nondepressed students, few differences were found between Australian and Japanese depressed patients. Thus, there appears to be an important interactional effect of culture and depression on decision making. The theoretical and clinical implications of the results are discussed. PMID- 1744629 TI - Neurochemical mechanisms of chronic antisocial behavior (psychopathy). A literature review. AB - This article reviews the important emotional correlates of chronic antisocial behavior from the standpoint of primary and secondary psychopathy. Primary psychopaths exhibit a conspicuous lack of empathetic emotions and secondary psychopaths exhibit a conspicuous excess of inappropriate emotions. The article points out the relationship between passive-avoidance learning deficits and primary psychopathy and between central nervous system serotonergic dysfunction and primary and secondary psychopathy. PMID- 1744630 TI - Posttraumatic stress disorder, depression, and somatic symptoms in U.S. Mien patients. AB - This report describes treatment over a period of 6 years of Mien refugees from highland Laos in the Indochinese Psychiatric Program of the Oregon Health Sciences University (Portland, OR). The medical and psychiatric problems of 84 patients were presented through somatic symptoms such as headache, dizziness, or musculoskeletal pain. Primary care medical problems were identified and treated, with the major focus on the two most common psychiatric diagnoses: major depression and posttraumatic stress disorder. Cultural beliefs about illness and medication interfered with adherence to prescribed treatment. A marked sensitivity to side effects of certain antidepressants also resulted in subtherapeutic doses. Patients rarely volunteered their traumatic histories, psychiatric problems, or dissatisfaction with medications. However, the effective use of medication for somatic complaints, along with the continuing recognition of Mien health beliefs in psychosocial treatments, allowed for the development of a trusting doctor-patient relationship and continued psychiatric care. PMID- 1744631 TI - Psychotherapy for dysthymia. A naturalistic study of ten patients. AB - Ten early and late onset dysthymia cases, diagnosed by DSM-III criteria, were treated with the Cognitive-Behavioral Analysis System of Psychotherapy, a standardized, three-stage therapy system developed specifically for the treatment of dysthymia. The cases are presented as naturalistic, direct-replication studies. Reliability of data trends within and across stages of treatment and generalization of effects across patients were demonstrated. The out-of-control depressive state at treatment outset is challenged by demonstrating to each patient that their depressive predicament is self-produced and maintained by maladaptive living strategies. The essential goals of therapy are teaching the patient a) to accept total responsibility for their depression and b) to achieve and maintain mood control by enacting adaptive daily living strategies. The progressive assumption of personal responsibility for the debilitative mood state is accompanied by a corresponding shift in a locus of control set from externality to internality. Patients were then taught situational coping strategies, and treatment ended when mood control was evinced. All cases were treated by J.P.M. The 10 cases met therapy termination criteria, and nine (one exception) were found in remission for dysthymia at follow-up of 2 years or more. Cognitive behavior psychotherapy, which directly attacks the helplessness and hopelessness plight of the dysthymic and teaches adaptive coping skills, appears to be an effective therapeutic strategy for the disorder. PMID- 1744632 TI - Dynamic treatment of panic disorder: a review. AB - A review was conducted of the psychoanalytic and psychodynamic literature in order to identify patients with panic disorder who received dynamic treatment. Thirty-five cases were located that fit the description of panic disorder. Their characteristics are compared with those of a current anxiety disorder clinic panic disorder population. Features of the successful dynamic treatment of panic disorder are summarized. PMID- 1744633 TI - Neuropsychological deficits in chronic schizophrenics. Relationship with symptoms and behavior. AB - Thirty-nine hospitalized chronic schizophrenics were administered the Luria Nebraska Neuropsychological Battery (LNNB) and the Weschler Adult Intelligence Scale-Revised when they were clinically stable. Test variables were related to Brief Psychiatric Rating Scale ratings and two behavioral measures of ward functioning, points and activities. Spearman correlations of test variables with the symptom and behavioral measures were entered into a series of median polish analyses. There was an overall significant relationship between the two sets of variables. Neuropsychological test variables that were most highly correlated with symptom/behavioral measures were LNNB Left Frontal, Memory, and Intellectual Processes scales. The positive symptoms of thought disorder and hallucinations were most consistently related to neuropsychological variables. In contrast with other findings in the literature, negative symptoms were not significantly correlated with neuropsychological performance. PMID- 1744634 TI - Involvement in an outreach and residential treatment program for homeless mentally ill veterans. AB - Descriptive data derived from initial assessment interviews and from standardized 3-month progress reports are presented on 1684 homeless, chronically mentally ill veterans who were contacted at nine sites in a national Department of Veterans Affairs outreach program. Levels of involvement in the program were modest, with only 16% of those screened having over 10 clinical contacts and 24% still involved after 3 months. Demographic and clinical characteristics were weakly associated with continued involvement, but those admitted to residential treatment were 5.4 times more likely to be involved in the program than those not admitted. Admission to residential treatment appears to be the strongest determinant of clinical engagement of the homeless mentally ill. PMID- 1744635 TI - Low dose desipramine treatment of cocaine-related panic attacks. AB - Thirteen patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia that started during or shortly after cocaine exposure were treated in the UCLA Anxiety Disorders Program (Los Angeles, CA). Low starting doses (ranging from 2.5 to 10 mg/day) of desipramine were used. Doses were then slowly increased to an average daily dose of 25 mg. Eleven patients who were able to tolerate an initial increase in panic anxiety responded to this treatment strategy with almost full resolution of panic attacks. The authors discuss the possible value and mechanisms of low dose treatment of cocaine-related panic attacks. PMID- 1744636 TI - Does a retrovirally encoded superantigen cause multiple sclerosis? PMID- 1744637 TI - Girolamo Fracastoro 1484-1553. PMID- 1744638 TI - The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography. AB - Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life. PMID- 1744639 TI - Dissection of the extracranial vertebral artery: report of four cases and review of the literature. AB - Four cases of cervical vertebral artery (VA) dissection are reported. In three patients VA dissection was associated with neck trauma. All patients were young or middle-aged (range 27 to 49 years). In two there was a history of migraine. Pain preceded neurological symptoms from hours to six weeks. Three patients had neurological deficits including elements of the lateral medullary syndrome, and one experienced recurrent transient ischaemic attacks in the vertebrobasilar territory. Angiographic findings included irregular stenosis, occlusion and pseudoaneurysm; in two patients VA abnormalities were bilateral. All patients were treated with anticoagulants and improved. In a review of 28 cases with traumatic dissection and 29 cases with spontaneous dissection of the VA reported in the literature, distinct clinical and angiographic features emerge. Aetiology remains obscure in most cases of spontaneous dissection and management is still controversial. PMID- 1744640 TI - The apomorphine test in parkinsonian syndromes. AB - The dopamine receptor agonist apomorphine has been used successfully to treat on off swings in Parkinson's disease. Its value as a predictor of dopa responsiveness in idiopathic Parkinson's disease (IPD) was assessed and its potential role in differentiating IPD from the Parkinsonian plus syndromes (PPS) of multisystem atrophy, progressive supranuclear palsy and olivopontocerebellar atrophy was investigated. The response to an injection of apomorphine was observed in 20 patients with IPD and eight with PPS after being off levodopa for 12 hours. Patients were reassessed after taking levodopa for one month. Nineteen of the 20 patients (95%) with IPD showed a positive response to apomorphine and 18 (90%) to oral levodopa. In the PPS group, two patients (25%) responded to the apomorphine injection but not to oral levodopa. Apomorphine produced severe drowsiness in the PPS patients. It is suggested that the test can predict dopa responsiveness in IPD and may be of help in confirming a doubtful diagnosis. It has potential value in differentiating IPD from PPS. PMID- 1744641 TI - The Chalfont Seizure Severity Scale. AB - Seizure severity has been largely neglected in studies of patients with epilepsy and the evaluations of treatment. A seizure severity scale, that measures the components of seizures that cause patients the most disturbance, is presented with an assessment of the scale's validity and reliability. PMID- 1744642 TI - The influence of stimulus properties on visual neglect. AB - Twenty five patients with right cerebral hemisphere damage and neglect participated in a series of bisection experiments. As expected, long lines were bisected to the right of true midpoint. By contrast, large circles and long white paper strips were bisected accurately, or with leftward errors. Small objects were less sensitive to stimulus properties: short lines and paper strips, and small circles, were bisected to the left of true midpoint, and these leftward errors were equally common as rightward errors with long lines. When asked to draw a perpendicular line of the same length as the presented horizontal line, patients overestimated the length of short lines but underestimated that of long lines. Presenting lines in near and far extrapersonal space selectively affected bisection of short lines. The results suggest that two opposing, independent mechanisms determine bisection performance in left neglect. PMID- 1744643 TI - The effect of posture on the normal and pathological auditory startle reflex. AB - The effect of posture on the EMG pattern of the normal auditory startle reflex was investigated. The startle response to an unexpected auditory tone was studied in eleven normal subjects when standing, and in six normal subjects when sitting relaxed or tonically plantar flexing both feet. Reflex EMG activity was recorded in the tibialis anterior and soleus about twice as frequently when standing, than when sitting relaxed. In addition, the median latencies to onset of reflex EMG activity in the tibialis anterior and soleus were about 40 and 60 ms shorter during standing, than when sitting relaxed. No short latency EMG activity was recorded in the calf muscles during tonic plantar flexion of the feet, while sitting. The effect of posture on the EMG pattern of the pathological auditory startle reflex was studied in five patients with hyperekplexia. In three patients the latency to onset of reflex EMG activity in the tibialis anterior was shorter when standing, than when sitting relaxed. The EMG pattern of the reflex response to sound was studied in detail in two of these patients and consisted of up to three successive components. The expression of each EMG component depended on the postural set of the limbs. In particular, a distinct short latency component was found in posturally important muscles following auditory stimulation. This short latency component was not recorded when sitting relaxed. It is concluded that the EMG pattern of the physiological and pathological auditory startle response is not fixed, but may change with the postural stance of the body. This finding supports the theory that the normal startle reflex and the abnormal startle reflex in hyperekplexia have a common brainstem origin. PMID- 1744644 TI - Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson's disease and atypical parkinsonism. AB - Striatal blood flow, glucose metabolism and 18F-Dopa uptake were studied with positron emission tomography (PET) in eight non-demented patients with idiopathic Parkinson's disease and eight with atypical Parkinsonism. Patients with atypical Parkinsonism had no specific cause for the Parkinsonian symptoms and were clinically different from Parkinson's disease with lack of resting tremor and a poor response to dopaminergic drugs. Decreased 18F-Dopa uptake in the putamen was observed in patients with Parkinson's disease and atypical Parkinsonism compared with normal controls. 18F-Dopa uptake in the head of the caudate was also significantly reduced in both conditions but relatively less in Parkinson's disease. Decreased blood flow and glucose metabolism in the striatum associated with a global cerebral decrease were also observed in patients with atypical Parkinsonism compared with controls, while they were preserved in patients with Parkinson's disease, indicating affected neurons not only in the striatum but also in the cerebrum in patients with atypical Parkinsonism compared with patients with Parkinson's disease. The differences in the caudate 18F-Dopa uptake, and blood flow and glucose metabolism in the cerebrum including the striatum between Parkinson's disease and atypical Parkinsonism assessed by PET may be due to the differences in the pathophysiological mechanism between Parkinson's disease and atypical Parkinsonism. PMID- 1744645 TI - Effects of alcohol on myoclonus and somatosensory evoked potentials in dyssynergia cerebellaris myoclonica. AB - Three brothers with dyssynergia cerebellaris myoclonica received alcohol to study the correlation between improvement of myoclonus and alteration in somatosensory evoked potentials (SEPs). Alcohol considerably improved myoclonus for about six hours in two patients (cases 1 and 2) but had only a mild effect in one (case 3). All three patients had giant cortical SEPs. The amplitudes of median N20-P25 and P25-N35 components and tibial N30-P40 and P40-N50 components were considerably decreased after alcohol ingestion in two patients (cases 1 and 2) but unchanged or slightly decreased in one (case 3). The peak latencies of those components were not affected by alcohol. There was thus a good correlation between the suppression of myoclonus and the decrease in giant SEP amplitude. PMID- 1744646 TI - Long-term cognitive deficits in patients after surgery on aneurysms of the anterior communicating artery. AB - The long term recovery of a series of 27 patients who had undergone rupture and repair of an aneurysm of the anterior communicating artery was assessed using a number of neuropsychological measures. Testing took place 12 to 84 months post surgery. On the basis of the results from tests of intellect, memory, and conceptual learning, three subgroups of patients were identified: those with persuasive cognitive defects, those with evidence of residual frontal lobe damage and those who showed no evidence of dysfunction. The occurrence of cerebral vasospasm was the most consistent predictor of long term cognitive deficit. PMID- 1744647 TI - The prognosis of primary intracerebral tumours presenting with epilepsy: the outcome of medical and surgical management. AB - It is not known whether conservative or early aggressive (resective surgery with or without radiotherapy) management is better for tumours presenting with epilepsy. The prognosis of 560 patients with a clinical and CT diagnosis of intrinsic supratentorial tumour was examined retrospectively. Epilepsy was the first symptom in 164 patients. Histological confirmation of diagnosis was available in 391 (70%) of cases. Median survival was 37 months in the group presenting with epilepsy and six months in those presenting with other symptoms (p less than 0.0001). Patients presenting with epilepsy were more likely to have a normal clinical examination, a non-enhancing low density lesion on CT scan and a low grade tumour. From Cox's stepwise proportional hazards model, significant independent variables adversely affecting prognosis were increasing age, focal neurological signs and enhancing CT lesions at diagnosis, non-resective surgery and male sex. Of those presenting with epilepsy 80 patients had surgical treatment within two months of CT diagnosis. The Cox's model failed to identify any beneficial effects for either early resective surgery or radiotherapy. In primary intracerebral tumours with presentations other than epilepsy, resective surgery and radiotherapy were amongst the important factors associated with prolonged survival. Primary intracerebral tumours presenting with epilepsy are relatively benign and their outcome appears to be chiefly determined by clinical factors. PMID- 1744648 TI - The workload of neurosurgeons: implications of the 1987 practice survey in the USA. AB - The number of neurosurgeons per million population is much lower in Europe than in the USA, where the point prevalence of neurosurgeons doubled between 1963-87. Results of a 1987 survey of USA neurosurgical practice show that surgery filled 25% of total time in professional activity. Of all cases treated, 64% were spinal disorders and 24% were intracranial disorders. Use of a relative value scale for neurosurgical procedures makes possible a rough and ready estimate of a neurosurgeon's weekly aggregate workload. However, the concept of a mean surgical workload must be examined within the context of the known variation of case mix and volume of surgical services in different practices. PMID- 1744649 TI - Radiological evidence of sinus infection in patients with multiple sclerosis. AB - The prevalence of radiological criteria of chronic sinus infection was compared in 42 cases of clinically definite or laboratory supported definite multiple sclerosis and 84 controls. No increase in relative risk of multiple sclerosis associated with the presence of chronic sinus infection was observed (odds ratio 1.2, 95% CI 0.5 to 3.1). The maxillary sinus was infected more often than the other paranasal sinuses but there was no difference in the distribution of infection within the sinuses between cases and controls. These results do not confirm an earlier report of an association between chronic sinus infection and multiple sclerosis. PMID- 1744650 TI - Olfactory impairment in motor neuron disease: a pilot study. AB - The ability to identify smells was tested in nine males and six females with motor neuron disease (MND) of varying severity, using the University of Pennsylvania Smell Identification Test (UPSIT). The olfactory impairment found in MND patients compared with age and sex matched controls is statistically significant at the 0.005 level. The relationship with Parkinson's disease, with Alzheimer's dementia and the possible aetiological implications of this new aspect of the MND are discussed. PMID- 1744651 TI - Pseudopseudohypoparathyroidism and spinal cord compression. AB - A 42 year old Greek male with pseudo-pseudohypoparathyroidism presented with difficulty in walking and with lower limb weakness. His physical signs included short stature, thick neck, short fourth metacarpals and metatarsals, and a spastic paraparesis. Serum calcium and phosphate and parathyroid concentrations were normal. Myelography demonstrated compression of the cervical and lumbar cord in association with local bony abnormalities. PMID- 1744652 TI - Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex. AB - Neuropathological findings in a 38 year old patient with dementia of frontal lobe type and motor neuron disease included pyramidal tracts, myelin pallor and neuron loss, gliosis and chromatolysis in the hypoglossal nucleus, together with frontal atrophy, neuron loss, gliosis and spongiosis in the upper cortical layers of the frontal (and temporal) lobes. Most remaining pyramidal and non-pyramidal neurons (multipolar, bitufted and bipolar cells) in the upper layers (layers II and III) of the frontal cortex (area B) had reduced dendritic arbors, proximal dendritic varicosities and amputation of dendrites as revealed in optimally stained rapid Golgi sections. Pyramidal cells in these layers also showed depletion of dendritic spines. Neurons in the inner layers were preserved. Loss of receptive surfaces in neurons of the upper cortical layers in the frontal cortex are indicative of neuronal disconnection, and are "hidden" contributory morphological substrates for the development of dementia. PMID- 1744653 TI - Ophthalmoplegic migraine and recurrent sinus arrest. PMID- 1744654 TI - Reversal of foot drop in sciatic nerve endometriosis. PMID- 1744655 TI - Should clinicians be given hard copies of duplex carotid ultrasound images? PMID- 1744656 TI - Hyperventilation tetany: effect of carbamazepine. PMID- 1744657 TI - Reversible pituitary stalk enlargement in cranial diabetes insipidus. PMID- 1744658 TI - Cardiovascular autonomic function tests--are three Valsalva's and six deep breaths necessary or will singles do? PMID- 1744659 TI - Benign relapsing meningo-myelitis. PMID- 1744660 TI - Creutzfeldt-Jacob disease following cadaveric dura mater graft. PMID- 1744661 TI - Cognitive impairments and depression in Parkinson's disease. PMID- 1744662 TI - Misconceptions and inappropriate use of terms in hyperthermic syndromes. PMID- 1744663 TI - Sexual function in patients with Parkinson's disease. PMID- 1744664 TI - Patient Self Determination Act. PMID- 1744665 TI - Caregiving stress among community caregivers for the elderly: does institutionalization make a difference? AB - Nurses in community settings are frequently exposed to elderly persons who receive a significant amount of physical and/or psychosocial support from one or more informal caregivers. Although numerous investigations exist examining stress and coping in persons who provide such care for elderly persons, little is known about the caregiver's status once full-time caregiving ceases. This study describes emotional and physical components of caregiving stress in a convenience sample of 124 caregivers. Of these, 31 had placed their charge in a nursing home, while 93 had not. A multivariate analysis of variance (MANOVA) between placed nonplaced groups revealed no significant differences in the total score or Role and Personal Strain subscales of the Burden Interview (J. Zarit & S. Zarit, 1983). Implications for community health nursing practice involve providing ongoing counseling and support of the caregiver and his or her charge, preparing both for the placement experience should it be indicated, and continued follow-up care post-placement. Greater collaboration between community-based and institutionally based nurses can facilitate implementation of these strategies. PMID- 1744666 TI - Home visiting outcomes and quality of life measures. AB - Public Health agencies are faced with the task of self-evaluation. For years, they have evaluated themselves solely through utilization as demonstrated by the numbers of patients that they have served. A new thrust is to change the methods of evaluation by devising and implementing a quality assurance (QA) system. Traditional QA systems focus on acutely ill patients and are based on the medical model. In contrast, public health focuses on well or chronically ill patients with services that involve mostly palliative treatment, disease prevention, and/or health promotion. The criteria used by hospitals do not apply. Thus, public health agencies are forced to review their standards and develop criteria applicable to public health. This re-examination of public health can stimulate new ways of viewing old programs and therefore, elicit information that has never been gathered before. PMID- 1744667 TI - Self-image among early adolescents: revisited. AB - Early adolescence is the developmental period during which children make the physical, psychological, cognitive, and social transitions to adolescence. Because the development of a healthy conceptualization of the self is foundational to adequate functioning later in life, self-image is a concept of interest to clinicians and researchers. Offer, Ostrov, and Howard (1981) conducted considerable research in the area and demonstrated that early adolescents have the capacity for self-reflection and are willing to share their reflections with others. Most early adolescents tend to be self-conscious due, chiefly, to the numerous physical and emotional changes occurring during this time period (M. P. Strommen & A. L. Strommen, 1985). Behavior is characterized by moodiness, impulsiveness, peer influence (Robin, 1985), and a growing resistance to authority. These factors usually result in an awkward child attempting to exert independence in an unprecedented fashion about a variety of topics (Manning, 1983). The purpose of this study was to investigate the self-image of early adolescents, aged 11 to 14 years, in order to plan for the health and developmental needs of middle school children and their families. Survey data were collected to answer the questions: (a) What is the self-image of a representative sample of middle school students in the community?; and (b) Are there differences in self-image based on gender, race, and parental occupation? PMID- 1744668 TI - Six years after an economic crisis: child's anxiety and quality of peer relationships. AB - The purpose of this 6-year follow-up study was to determine whether there is a long-term relationship between economic stress and childrens' anxiety and peer related behaviors. Data were collected from 39 of the 52 families in the original study. Analysis resulted in several interesting findings. Economic stress in 1983 was a moderate predictor of state anxiety, trait anxiety, and peer rejection in girls in 1989. Descriptive evidence was provided to indicate that detrimental effects of economic stressors on the family as a unit continue beyond the initial stress event. Implications for community health nurses (CHNs) are addressed. PMID- 1744669 TI - Technological dependency: a preliminary model and pilot of home total parenteral nutrition. AB - As hospital costs increase and durations of hospital stays decrease, clients are being discharged to home care in more acute states and often with demands for high technology therapy. To assist in understanding the experiences families face in adapting to either short- or long-term dependence on technology, a model was developed from literature and research review. The literature review suggested that self-care practices affected each of the family members' adaptation. The model was developed to indicate self-care issues and problems impacting adaptation to high technology at home. A pilot study was conducted to determine if interviews and questionnaires would collect data necessary to test the model. This article describes the pilot study results. Data indicated that relationships and role changes did occur after the family became technologically dependent. Also, although depression and anxiety were common responses, the family members felt capable and successful in their caregiving roles. PMID- 1744670 TI - Comparative effects of cuff size and tightness of fit on accuracy of blood pressure measurements. AB - To determine the effect of snugness of cuff wrap on the accuracy of blood pressure (BP) measurements, we performed two studies on 6 healthy volunteers. In both studies, control values were obtained from the right upper arm with cuffs of appropriate size and snug fit. Study 1 had two phases. In the first, cuffs of appropriate size were wrapped snugly around the upper left arm of seated subjects. The effects of two other degrees of cuff snugness on the measurement of BP were evaluated by placing a filled 250-mL intravenous fluid bag between the cuff and arm over the triceps, measuring BP, then draining the same bag of half its contents and then all of its contents without rewrapping the cuff ("loose," "very loose" fit), each time measuring BP. The second phase of study 1 was identical in procedure, except that the cuffs used on the left arm were one size too small. In study 2, the experimental cuffs were placed just above the right ankle. To alter the signal-to-noise ratio, BP was raised or lowered: the standing position elevated mean BP by an average of 90 mm Hg, and elevation of the legs decreased mean BP by an average of 43 mm Hg. In study 1, we found that appropriately sized cuffs, whether wrapped tightly or loosely, gave correct BP readings. Cuffs snugly wrapped, but too small for the subject, gave high BP readings, on the average by approximately 10 mm Hg. Loose wrapping of small cuffs gave variable results in individual subjects that exaggerated systolic BP from 2 to 80 mm Hg. In study 2, elevating the legs or standing decreased or increased BP consistently. Loose wrapping of appropriately sized cuffs around the ankles of the subjects had no additional significant effect on BP. PMID- 1744671 TI - End-tidal carbon dioxide pressure in neonates and infants measured by aspiration and flow-through capnography. AB - In 25 anesthetized, intubated, artificially ventilated, and paralyzed healthy neonates and infants, end-tidal PCO2 (PETCO2) measured by remote multiplexed mass spectrometry was 1.86 +/- 1.58 mm Hg lower than arterial PCO2 (PaCO2). PETCO2 measured by a flow-through cuvette was 1.02 +/- 1.64 mm Hg lower than PaCO2. The difference between the two methods of capnography was not significant. Values for PETCO2 obtained by mass spectrometry changed -0.43 +/- 1.43 mm Hg from baseline after 15 minutes of aspiration at a sample flow rate of 240 ml/min. Values for PETCO2 obtained with flow-through capnography changed -0.17 +/- 2.17 mm Hg from baseline after 15 minutes. In both methods, the changes from baseline in PETCO2 over time were not significant. These results suggest that both methods of capnography studied are reliable and may be used safely in neonates despite high sample flow rates and added apparatus dead space (0.6 ml for tracheal tubes less than or equal to 4.0 mm OD and 4.9 ml for tracheal tubes greater than 4.0 mm OD). PMID- 1744672 TI - Clinical utility of a colorimetric end-tidal CO2 detector in cardiopulmonary resuscitation and emergency intubation. AB - The purposes of this study were to evaluate the clinical utility of a colorimetric end-tidal CO2 (ETCO2) detector in confirming proper endotracheal intubation in patients requiring emergency intubation, to determine if this new device can be used as an adjunct to judge the effectiveness of cardiopulmonary resuscitation (CPR), and to determine whether the device can predict successful resuscitation from cardiopulmonary arrest. We studied prospectively 110 patients requiring emergency intubation for either respiratory distress (53 patients) or cardiopulmonary arrest (57 patients) by recording the color range of the indicator after the initial intubation. In patients who suffered a cardiopulmonary arrest, the color range was also recorded during CPR after the endotracheal tube was confirmed to be in the tracheal position and perfusion optimized, and at the moment CPR was stopped. The ETCO2 detector was 100% specific for correct endotracheal intubation in all patients. It was also highly sensitive (0.98) for correct endotracheal intubation in patients with respiratory distress. However, it was not sensitive (0.62) in patients with cardiopulmonary arrest and low perfusion. The sensitivity improved (0.88) when we used the ETCO2 range obtained after attempts to increase perfusion. A low ETCO2 color range in 19 patients undergoing CPR was interpreted as low cardiac output and prompted the physicians to attempt to increase perfusion. Of the patients who underwent CPR, no patient whose ETCO2 level remained less than 2% was successfully resuscitated. Those patients who had an ETCO2 level greater than or equal to 2% had a significantly higher incidence of successful resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744673 TI - A noninvasive method of estimating mean pulmonary artery pressure in the pneumatic total artificial heart. AB - Accurate hemodynamic monitoring is essential for the clinical management of the recipient of a total artificial heart (TAH). The high incidence of pulmonary congestive disorders in this population complicates this already formidable task. Lack of diagnostic pulmonary artery pressure (PAP) information is recognized as a fundamental source of these problems. Because conventional methods of obtaining hemodynamic information are difficult to implement in TAH recipients, improvement of TAH case management depends on the development of innovative monitoring strategies. Noninvasive monitoring techniques have been developed for three (right atrial pressure, left atrial pressure, and aortic pressure) of the four auxiliary circulatory pressures used to quantify hemodynamic performance. Development of the fourth, for PAP, was the subject of this work. We developed a noninvasive, in vitro method of estimating mean PAP in the Jarvik-7 TAH (Symbion, Inc, Salt Lake City, UT) recipient. This information was obtained by analyzing the relationship between the pneumatic right drive pressure (RDP) and PAP waveforms produced by a Jarvik-7 (70 ml) connected to a Donovan mock circulation and driven by a Utahdrive System IIIe Controller (Symbion, Inc, Salt Lake City, UT). Total artificial heart driver parameters (i.e., heart rate, percent systole, and vacuum) were manipulated to produce a range of ventricular filling volumes (FV), from 40 to 60 ml, for three distinct states of the pulmonary vasculature: hypotensive, normal, and hypertensive. A unique multiple-linear regression equation was derived for each FV from the RDP-PAP relationship exhibited under these conditions. Comparison of computed estimates of PAP with actual measurements showed overall average correlations of greater than 0.92, with a standard error of the estimate of less than 1.9 mm Hg. The mean difference between actual and computed PAP measurements was -0.03 +/- 2.0 Hg. Estimations were accurate within 8.5% of true PAP values. Additional experimentation revealed that while the RDP-PAP relationships are dependent on FV, they are independent of the manner in which FV was obtained. Estimates proved useful over the clinical operating range of the pneumatic heart driver, as well as over the normal physiologic range of PAP in the human. This method is readily applicable to a computer-based monitoring implementation, although its effectiveness needs to be demonstrated in vivo. PMID- 1744674 TI - Noninvasive Doppler blood pressure monitoring in the monoplace hyperbaric chamber. AB - We describe a noninvasive method of monitoring blood pressure in the monoplace hyperbaric chamber. A standard blood pressure cuff was placed on the patient's arm. A Doppler probe, linked to an ultrasonic Doppler flow detector outside the chamber, was secured over the patient's radial artery. Cuff inflation tubing and the Doppler probe wires were passed into the chamber by modifying a standard disposable hyperbaric intravenous pass-through. Blood pressure readings were determined by inflating and slowly deflating the cuff from outside the chamber while observing the sphygmomanometer within the chamber and listening for the first audible flow signal from the Doppler detector, corresponding to the systolic blood pressure. To minimize the risk of fire in the oxygen-filled monoplace hyperbaric chamber, the patient, Doppler detector, and chamber were grounded. Doppler readings obtained from nine normal subjects whose arterial pressures were being measured with indwelling radial arterial catheters (approved as part of another study by the hospital's Investigational Review Board) compare closely with the subject's blood pressures measured with this noninvasive method: 114 +/- 7.6 mm Hg (mean +/- 1 SD) compared to 112 +/- 8.1 mm Hg, respectively (n = 92 measurements in 8 subjects). We conclude that this noninvasive method of monitoring blood pressure within the monoplace hyperbaric chamber is accurate and suitable for monoplace clinical purposes. PMID- 1744675 TI - Erroneous mass spectrometer data caused by a faulty patient sampling tube: case report and laboratory study. AB - We report an error due to faulty sampling of gas for mass spectrometry by side stream analysis that occurred during a general anesthetic for a surgical procedure. Two defects in the patient sampling tube were present. First, a crack was discovered in the polyvinylchloride tubing at the connection to the patient circuit. Second, secretions had accumulated in the end of the tubing that caused a partial obstruction to gas sampling. This combination promoted the contamination of respiratory gases sampled from the anesthesia circuit with entrained room air. This entrainment, however, occurred only during exhalation while ventilation was being controlled with a descending (during exhalation) bellows. The particular sampling error was reproduced and characterized in a mock circuit to simulate the sampling tube defects. It was determined that both a leak and a partial obstruction were necessary conditions for the sampling error to exist. PMID- 1744676 TI - Eliminating diathermy-induced artifacts during intraoperative monitoring of somatosensory-evoked potentials: a hardware solution. AB - Somatosensory-evoked potentials (SEPs) recorded intraoperatively are often contaminated by artifacts arising from unipolar diathermy. This increases variability in serial SEP recordings and decreases the reliability of SEPs for intraoperative monitoring. Rejection of single sweeps on the basis of a voltage criterion can only partially prevent the inclusion of sweeps containing artifacts. We describe a low-cost hardware system that will halt SEP acquisition automatically before diathermy becomes active. Activation of the diathermy switch will halt SEP acquisition by sending a digital inhibit signal to the evoked potential machine via a fiberoptic cable. A timer delays the activation of the diathermy until the last sweep has been completed. To allow the electroencephalographic amplifiers to recover from any overload condition resulting from the high-voltage/high-frequency input during diathermy, acquisition is resumed only after a user-selectable time interval. The system was evaluated in 50 patients. It effectively interrupted SEP acquisition each time diathermy was used. By eliminating diathermy noise from the averaged waveforms, the system will allow evoked potential monitoring even during periods of intensive use of diathermy. PMID- 1744677 TI - Cerebral oxygen monitoring with near infrared spectroscopy: clinical application to neonates. AB - Near infrared spectroscopy is a new noninvasive optical method for bedside monitoring of cerebral oxygenation. It uses differential absorbance of near infrared light to assess relative changes in the oxidation-reduction state of cytochrome aa3, as well as changes in the amounts of oxyhemoglobin, deoxyhemoglobin, and blood volume in the monitored field. Although this technique is applicable to all ages and sizes of patients and to multiple clinical settings, the majority of clinical studies to date have focused on the neonate. These studies have demonstrated its potential for advancing neonatal care and in understanding how diseases and therapies affect cerebral oxygenation. This paper reviews the near infrared spectroscopy technique and summarizes its potential applications in the field of neonatal intensive care. PMID- 1744678 TI - A regularity statistic for medical data analysis. AB - A new statistic has been developed to quantify the amount of regularity in data. This statistic, ApEn (approximate entropy), appears to have potential application throughout medicine, notably in electrocardiogram and related heart rate data analyses and in the analysis of endocrine hormone release pulsatility. The focus of this article is ApEn. We commence with a simple example of what we are trying to discern. We then discuss exact regularity statistics and practical difficulties of using them in data analysis. The mathematic formula development for ApEn concludes the Solution section. We next discuss the two key input requirements, followed by an account of a pilot study successfully applying ApEn to neonatal heart rate analysis. We conclude with the important topic of ApEn as a relative (not absolute) measure, potential applications, and some caveats about appropriate usage of ApEn. Appendix A provides example ApEn and entropy computations to develop intuition about these measures. Appendix B contains a Fortran program for computing ApEn. This article can be read from at least three viewpoints. The practitioner who wishes to use a "black box" to measure regularity should concentrate on the exact formula, choices for the two input variables, potential applications, and caveats about appropriate usage. The physician who wishes to apply ApEn to heart rate analysis should particularly note the pilot study discussion. The more mathematically inclined reader will benefit from discussions of the relative (comparative) property of ApEn and from Appendix A. PMID- 1744679 TI - Intra-aortic balloon pump prevents transtracheal Doppler endotracheal tube measurements of cardiac output. PMID- 1744681 TI - Society for Neuroanesthesia and Critical Care bibliography. PMID- 1744680 TI - Pulse oximetry during transport of the critically ill. PMID- 1744682 TI - Computerization of anesthesia information management--users' perspective. PMID- 1744683 TI - Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells. AB - Biopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36 +/- 0.44 vs. 11.42 +/- 2.32 nmol/10(6) cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals. PMID- 1744684 TI - Primary glial tumor patients treated by combining cis-platin and etoposide. AB - Thirty eight patients with malignant gliomas (27 GBM and 11 AA) were treated with up to 7 cycles of CDDP + VP16 every month after surgery. Chemotherapy was planned as two cycles before and 5 cycles after radiation (42 Gy) using a three times daily fractionation schedule. No severe toxicity was observed. The object of our study was to investigate the antitumor effectiveness by combining CDDP plus VP16 against primary malignant glial tumors. The time to tumor progression (TTP) and survival time (ST) of the GBM patients in the present study were 38.5 and 68.5 weeks respectively. The TTP of the AA patients was 73 weeks and the ST was not calculated as most patients are still alive. By the 18th. month after surgery, 38% of GBM and 74% of AA patients treated with (CDDP + VP16) are still alive. This study demonstrates that the combination of CDDP and VP16 is effective in patients with malignant gliomas. PMID- 1744685 TI - Intravascular lymphomatosis (neoplastic angioendotheliosis) of the central nervous system: case report and literature review. AB - A 63-year-old woman developed gradual slowness, recurrent multifocal deficits, severe constitutional symptoms and hypopituitarism which progressed to death over 2.5 months. Elevation in lactico dehydrogenases was the main biological abnormality. Necropsy showed an intravascular malignant proliferation which proved to be a lymphoma of B-lineage. In order to better define diagnostic criteria, we reviewed previously reported cases of intravascular lymphomatosis of the central nervous system. A strategy for establishing the diagnosis is proposed. PMID- 1744687 TI - Inhibition of glucocorticoid secretion by the hippocampal formation in the primate. AB - Inhibition of the adrenocortical axis by glucocorticoids (GCs) occurs at both hypothalamic and suprahypothalamic sites. In the rat, the hippocampus has been shown to be an essential suprahypothalamic site. The present study shows that the hippocampal system serves a similar role in the nonhuman primate. Bilateral lesions that included the hippocampal formation and the parahippocampal cortex; the hippocampal formation, parahippocampal cortex, and the amygdala; or the fornix all produced GC hypersecretion in cynomolgus monkeys. The hypersecretion occurred throughout the day. Moreover, these lesions were also associated with dexamethasone resistance (i.e., GC hypersecretion following administration of the synthetic GC dexamethasone). The hypersecretion could not be attributed to acute surgical trauma, because neither circumscribed lesions of the amygdala nor conjoint lesions of the perirhinal and parahippocampal cortex produced adrenocortical abnormalities. Finally, in agreement with data derived from the rat, the GC hypersecretion following hippocampal lesions was transient. Secretory activity returned to normal levels by 6-15 months in all operated groups. Thus, the primate hippocampal system appears to share some neuroendocrine functions with the rodent. PMID- 1744688 TI - The molecular and pharmacological properties of muscarinic cholinergic receptors expressed by rat sweat glands are unaltered by denervation. AB - Previous studies have indicated that denervation of adult rodent sweat glands results in the loss of secretory responsiveness to muscarinic agonists. To elucidate the molecular basis of this loss, we have characterized the muscarinic cholinergic receptor present in adult rat sweat glands and examined the effects of cholinergic denervation on its properties and expression. When homogenates of gland-rich tissue from adult animals were assayed with [N-methyl-3H]-scopolamine, a high-affinity muscarinic antagonist, the concentration of muscarinic receptors was 301 fmol/mg protein and the affinity was 131 pM. Autoradiographic analysis demonstrated that ligand binding sites were detectable only on glands. In competition studies with well-characterized muscarinic agents, the receptor exhibited typical muscarinic pharmacology. Further investigation with the selective muscarinic antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide, pirenzepine, and AF DX-116 revealed that the sweat gland receptor belongs to the M2 glandular pharmacological subtype. In situ hybridization histochemistry with receptor subtype-specific oligonucleotide probes indicated that rat sweat glands express the m3 molecular receptor subtype. Seven days after sciatic nerve transection, when denervated glands were compared to those on the contralateral unoperated side, there was no significant difference either in the concentration or affinity of muscarinic binding sites or in receptor density or distribution. Furthermore, the molecular subtype and the level of its expression were unchanged. Thus, it appears that muscarinic binding sites and m3 receptor mRNA are present in denervated sweat glands that are unresponsive to muscarinic stimulation. These results suggest that the regulation of responsiveness occurs at a point distal to the expression of muscarinic receptors. PMID- 1744689 TI - Developmental expression of muscarinic cholinergic receptors and coupling to phospholipase C in rat sweat glands are independent of innervation. AB - During development, the innervation of rat sweat glands undergoes a striking change from noradrenergic to cholinergic function. The acquisition of secretory responsiveness by the glands is temporally correlated with the appearance of cholinergic properties. In addition, responsiveness fails to appear in the absence of innervation. To investigate the basis of the onset of functional transmission and secretory responsiveness and its possible relationship to innervation, we analyzed the development of muscarinic cholinergic receptors in sweat glands, examined their expression in the glands of adult rats sympathectomized at birth, and assayed the ability of muscarinic agonists to increase phosphoinositide (PI) turnover. Autoradiographic and in situ hybridization analysis revealed that muscarinic ligand binding sites were first detectable as glands begin to form on postnatal day 4 (P4). Between P4 and P14, receptor concentration increased in parallel with mRNA for the m3 receptor subtype. On P14, the concentration of ligand binding sites approached adult levels, although only a small proportion of glands at this age secrete in response to nerve stimulation or cholinergic agonists. When the pharmacological properties of muscarinic receptors in sweat glands of adult rats sympathectomized at birth were compared to those of normal glands, the concentration and affinity determined with [N-methyl-3H]-scopolamine and the Ki values determined with the subtype-selective muscarinic antagonists 4-DAMP, pirenzepine, and AF DX-116 were similar. In addition, the molecular subtype was unchanged as was the level of m3 message. Studies of PI turnover in response to muscarinic stimulation indicated that the receptors expressed in sweat glands isolated from sympathectomized and acutely denervated, as well as control, rats were functionally coupled to phospholipase C. The absence of sympathetic innervation therefore does not appear to influence either the development of muscarinic receptors or their coupling to PI turnover. Our results suggest that functional sympathetic cholinergic innervation plays a central role in the development and maintenance of secretory function at a step distal to signal transduction across the cell membrane. PMID- 1744690 TI - Processing of beta-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. AB - Microglial cells and astrocytes are closely associated with nearly all compact deposits of the amyloid beta-protein found in the senile plaques characteristic of Alzheimer's disease and trisomy 21. The biosynthesis and metabolic fate of the beta-amyloid precursor protein (beta APP) in astrocytes has not been characterized, and its identification in microglia has not been described. Here, we report the expression of beta APP by astrocytes and microglia in primary cultures of cerebral cortex from newborn rats. Using metabolic labeling followed by immunoprecipitation, we show that both astrocytes and microglia express substantial amounts of the major isoforms of beta APP. This is confirmed by PCR mediated amplification of the corresponding mRNAs, showing that all three major transcripts (beta APP695, beta APP751, and beta APP770) are present in relatively equal amounts. Despite rapid turnover of the precursor, astrocytes and microglia show a reduced production of soluble fragments of beta APP compared to cells transfected with beta APP cDNAs. The relative amount of soluble beta APP molecules generated is both cell type and isoform specific. Immunocytochemistry reveals that full-length beta APP is located in internal membranous vesicles, with only very little insertion at the cell surface. The latter data are in agreement with the reduced ability of microglia and astrocytes to cleave the beta APP into soluble derivatives. Our findings indicate that both astrocytes and microglia strongly express all three major forms of beta APP but apparently process these molecules by an alternative pathway that generates very small amounts of soluble beta APP. The immunocytochemical localization and the biochemical data lead to the suggestion that beta APP may not function principally as a cell surface or secreted protein in vivo but may have an important intracellular function. PMID- 1744691 TI - A computational model for the overall pattern of ocular dominance. AB - In layer IV of the primary visual cortex, in both the macaque monkey and the cat, geniculocortical terminals representing the two eyes are segregated into alternating zones known as ocular dominance bands. Viewed tangentially, in the monkey these bands take the form of a series of branching parallel stripes that run roughly perpendicular to the border of striate cortex. In the cat, the overall ocular dominance pattern consists of irregularly branching, beaded bands that exhibit no predominant orientation. If the striking differences in the appearance of these two patterns reflect important differences in the basic rules governing cortical ocular dominance, then this poses a problem for attempts to formulate general principles of visual cortical organization. However, it has been suggested that the differences in the appearance of the ocular dominance patterns in these two species could result simply from known differences in the boundary conditions of their geniculocortical pathways. This article describes the formulation and testing of a single computational model that accurately predicts the quite dissimilar ocular dominance patterns in cats and monkeys. This model also generalizes to predict the different ocular dominance patterns observed in young and old three-eyed frogs, supporting the notion that the overall pattern of ocular dominance is governed by a common set of rules. The significance of these results is discussed in terms of previous models, which have focused largely on local processes underlying the development of ocular dominance segregation. Although the present model is not a developmental one, it does shed some light on potential mechanisms for establishing retinotopy in striate cortex and on possible developmental relationships between the geniculostriate pathway and intrinsic modularity of the striate cortex. PMID- 1744686 TI - Neuro-oncology index and review (adult primary brain tumors). Radiotherapy, chemotherapy, immunotherapy, photodynamic therapy. PMID- 1744692 TI - Vacuous jaw movements and feeding deficits in rats with ventrolateral striatal dopamine depletion: possible relation to parkinsonian symptoms. AB - A series of experiments examined the effects of regional dopamine depletions produced by intrastriatal injections of 6-hydroxydopamine on voluntary and involuntary movements in rats. Depletion of dopamine in the ventrolateral striatum produced a substantial decrease in food intake, from which the animals recovered. Rats with dopamine depletions in anteroventromedial or dorsolateral striatum did not have significant feeding deficits. Rats with ventrolateral dopamine depletions showed no deficits in locomotor activity or rearing behavior; however, depletions of dopamine in dorsolateral striatum significantly reduced rearing. Vacuous jaw movements that resemble chewing were produced by dopamine depletion in the ventrolateral striatum, but not the anteroventromedial or dorsolateral striatum. Systemic administration of haloperidol (0.4 mg/kg) increased vacuous chewing responses in dopamine-depleted and control rats. Thus, vacuous chewing responses can result from reduced functional activity of striatal dopamine, and these responses share some characteristics with human parkinsonian symptoms. In addition, these data support the notion that the neostriatum is functionally heterogeneous and that the ventrolateral region is particularly important for oral motor control. PMID- 1744693 TI - Influence of spinal cord stimulation on the innervation pattern of muscle fibers in vivo. AB - In chick embryo, chronic stimulation of the brachial spinal cord at a fast rhythm from days 7 to 18 of development induced an increase in AChE activity sites and ACh receptor (AChR) clusters in slow anterior latissimus dorsi (ALD) muscle. Most AChR clusters and AChE spots were contacted by nerve endings. A previous study showed that such spinal cord stimulation causes changes in ALD muscle properties, especially the appearance of a high proportion of fast type II fibers (Fournier Le Ray et al., 1989). Analysis of the synaptic pattern in different fiber types of experimental ALD muscle indicated a decrease in the distance between successive AChE spots in slow type III fibers compared to controls, whereas the intersynaptic distance in fast type II fibers was very similar to that in the rare fast fibers developing in control ALD. Fast fibers of experimental muscles exhibited less AChR than did slow fibers. The increased number of neuromuscular junctions in ALD muscle after spinal cord stimulation appeared to be preferentially located in slow fibers. Electron microscopy showed no change in the number of axons in ALD nerve after spinal cord stimulation. The activity imposed on brachial motoneurons apparently caused terminal sprouting of ALD nerve in target muscle, thus accounting for the increase in neuromuscular contacts in ALD muscle fibers. Differences in the distribution of nerve contacts indicate that the type of muscle fiber innervated may play a critical role in the synaptic pattern during chick embryogenesis. PMID- 1744694 TI - Muscarinic agonists activate an inwardly rectifying potassium conductance in medial pontine reticular formation neurons of the rat in vitro. AB - Intracellular recordings were obtained from neurons in pontine reticular formation slices of the rat to characterize a cholinergic-gated increase in conductance. The conductance increase was associated with a hyperpolarization of the membrane potential and with an outward current under voltage-clamp conditions. Current-voltage relations and potassium substitution experiments indicated mediation by a change in permeability, primarily to potassium. This potassium conductance exhibited inward rectification at membrane potentials negative to resting potential, a novel finding for cholinergic actions in CNS neurons. Further characterization of this inwardly rectifying potassium conductance revealed marked sensitivity to low concentrations of barium. Cholinergically evoked currents were relatively unaffected by the presence of extracellular cesium. Cholinergic effects persisted in TTX. The outward currents elicited by carbachol or methacholine were blocked only by high concentrations of pirenzepine, a selective antagonist of the M1 muscarinic receptor. The interaction between these agents is quantitatively consistent with cholinergic action at postsynaptic muscarinic receptors of the non-M1 subtype. PMID- 1744695 TI - Normally unused positional cues guide ectopic afferents in the leech CNS. AB - Central projections from peripheral sensory neurons segregate into distinct, ventrally positioned longitudinal tracts within the segmental ganglia of the leech Hirudo medicinalis. As documented here, there is an additional tract in the neuropils of the fifth and sixth body ganglia, located at the lateral margin and formed by afferent axons (the "sex afferents") originating from sensory neurons located in the male and female genitalia. Ablation of the genitalia results in the complete absence of this additional tract. We asked (1) whether segmental differences exist in the distribution of pathway cues available to the sex afferents, and (2) whether central pathway selection by these axons is specific. We transplanted the primordia of the male genitalia to several ectopic positions posterior to the sixth body segment and labeled the ectopic sex afferents in order to examine their paths in the CNS. In about 50% of the experimental animals, afferent axons originating in the transplanted tissue segregated into a distinct lateral fiber bundle within the neuropil of a nearby ganglion, in a position corresponding to their normal one in the sex ganglia. The sex afferents therefore find their normal pathways even in the ganglia of inappropriate segments, although these pathways are not used by any other afferents in these ganglia. We propose, therefore, that the positional cues employed by afferent axons to select appropriate pathways in the ganglionic neuropil are expressed in all segments of the leech CNS, regardless of whether such cues are normally used by afferent axons in each segment. PMID- 1744696 TI - Testosterone differentially regulates the regenerative properties of injured hamster facial motoneurons. AB - We have previously demonstrated that systemic administration of testosterone accelerates functional recovery, as measured behaviorally, from facial paralysis induced by facial nerve crush axotomy in gonadectomized adult male hamsters. In this investigation, the hypothesis that testosterone enhances return of motor function by increasing the rate of axonal regeneration following injury was tested using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult castrated and intact males, and intact females, were subjected to right facial nerve crush axotomy at the stylomastoid foramen. One-half of the axotomized animals in each group received subcutaneous implants of testosterone, with the remainder of the animals sham implanted. Systemic administration of testosterone resulted in a 26-30% increase in the rate of regeneration of the fastest growing population of axons in the male experimental groups, regardless of whether the animal was castrated or not. This rate increase is similar to that observed in the conditioning lesion paradigm utilized by others. In the females, testosterone had a significant, but less pronounced, effect on the rate of axonal regeneration, which may be due in part to inherent gender-related differences in regenerative properties of facial motoneurons. A surprising finding of this study was that no shortening of the delay of sprout formation by testosterone was observed across the various experimental groups. These data suggest that the mechanism by which gonadal steroids act in the injured nervous system is partly through the differential regulation of the regenerative properties of the injured cell, presumably via hormone receptor mediated action at the level of the neuronal genome. PMID- 1744697 TI - Spontaneous action potential activity and synaptic currents in the embryonic turtle cerebral cortex. AB - We used loose-patch and whole-cell recording techniques to study the development of spontaneous action potential activity and spontaneous excitatory and inhibitory synaptic currents in embryonic neurons in the cerebral hemispheres of turtles. Sporadic action potential activity appeared early in development at stage 17, soon after morphologically identifiable pyramidal and nonpyramidal neurons were first observed in the cortex. As the cortical plate matured in midembryonic stages, action potential activity became more regular and fell into one of two distinct patterns, tonic and intermittent high-frequency firing. Spontaneous excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) appeared at developmental stages 18 and 20, respectively, after action potential activity was established. EPSCs and IPSCs exhibited characteristic ionic dependence and pharmacology throughout development. EPSCs reversed in direction at the equilibrium potential for cations and were sensitive to 6-cyano-7 nitroquinoxaline-2,3-dione, an antagonist of the non-NMDA type of glutamate receptor. IPSCs reversed at the equilibrium potential for chloride and were sensitive to bicuculline methiodide, a GABAA receptor antagonist. Spontaneous synaptic currents differed in their time course of development and in waveform parameters. Spontaneous synaptic currents differed in their time course of development and in waveform parameters. Spontaneous EPSCs appeared at stage 18 and increased progressively in frequency, from 0.2 +/- 0.1 Hz at stage 20 to 3.2 +/- 2.0 Hz at stage 26 (hatching), while spontaneous IPSCs appeared at stage 20 and surpassed EPSCs in frequency, increasing to 7.1 +/- 1.6 Hz at stage 26. EPSCs exhibited stable amplitudes during development, with a mean conductance of 126 +/ 20 pS at stage 26, while IPSCs increased in mean amplitude, from 180 +/- 12 pS at stage 18 to 260 +/- 44 pS at stage 26. The rise time to peak conductance of both types of synaptic currents increased with developmental time, for EPSCs increasing from 1.5 +/- 0.5 msec at stage 20 to 2.7 +/- 0.6 msec at stage 26 and for IPSCs increasing from 2.9 +/- 0.2 msec at stage 18 to 6.2 +/- 0.8 msec at stage 26. While the decay time constants increased for EPSCs, from 3.9 +/- 1.2 msec at stage 20 to 8.7 +/- 2.3 msec at stage 26, decay time constants for IPSCs showed a decreasing trend from 24.0 +/- 5.2 msec at stage 18 to 18.4 +/- 5.3 msec at stage 26. The excitatory and inhibitory synaptic currents were sensitive to the sodium channel blocker TTX and were thus dependent, in part, on spontaneous action potential activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1744698 TI - Antagonism of central growth hormone-releasing factor activity selectively attenuates dark-onset feeding in rats. AB - Exogenous growth hormone-releasing factor (GRF) has been shown to activate feeding by central mechanisms involving the suprachiasmatic nucleus/medial preoptic area (SCN/MPOA). Until now, however, the role played by endogenous GRF in the SCN/MPOA in naturally occurring eating has remained unknown. To investigate this, the effects of SCN/MPOA injections of GRF antiserum (AS-GRF) on feeding in rats were studied. In light of SCN involvement in the control of circadian rhythms, AS-GRF was tested during the light and dark phases of the photoperiod. Results indicated that AS-GRF significantly attenuated dark-onset feeding but had no effect on feeding during the mid-dark, mid-light, or light onset periods. These results suggest that endogenous GRF does play a role in naturally occurring feeding and that it may be involved in the circadian organization of feeding. PMID- 1744699 TI - Sodium-bicarbonate cotransport in retinal Muller (glial) cells of the salamander. AB - An electrogenic Na+/HCO3- cotransport system was studied in freshly dissociated Muller cells of the salamander retina. Cotransporter currents were recorded from isolated cells using the whole-cell, voltage-clamp technique following the block of K+ conductance with external Ba2+ and internal Cs+. At constant pHo, an outward current was evoked when extracellular HCO3- concentration was raised by pressure ejecting a HCO3(-)-buffered solution onto the surface of cells bathed in nominally HCO3(-)-free solution. The HCO3(-)-evoked outward current was reduced to 4.4% of control by 0.5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2' disulfonate), to 28.8% of control by 2 mM DNDS (4,4'-dinitrostilbene-2,2' disulfonate), and to 28.4% of control by 2 mM harmaline. Substitution of choline for Na+ in bath and ejection solutions reduced the response to 1.3% of control. Bicarbonate-evoked currents of normal magnitude were recorded when methane sulfonate was substituted for Cl- in bath, ejection, and intracellular solutions. Similarly, an outward current was evoked when extracellular Na+ concentration was raised in the presence of HCO3-. The Na(+)-evoked response was reduced to 16.2% of control by 2 mM DNDS and was abolished by removal of HCO3- from bath and ejection solutions. Taken together, these results (block by stilbenes and harmaline, HCO3- and Na+ dependence, Cl- independence) indicate that salamander Muller cells possess an electrogenic Na+/HCO3- cotransport system. Na+/HCO3- cotransporter sites were localized primarily at the endfoot region of Muller cells. Ejection of HCO3- onto the endfoot evoked outward currents 10 times larger than currents evoked by ejections onto the opposite (distal) end of the cell. The reversal potential of the cotransporter was determined by DNDS block of cotransport current. In the absence of a transmembrane HCO3- gradient, the reversal potential varied systematically as a function of the transmembrane Na+ gradient. The reversal potential was -0.1 mV for a [Na+]o:[Na+]i ratio of 1:1 and -25.2 mV for a Na+ gradient ratio of 7.4:1. Based on these values, the estimated stoichiometry of the cotransporter was 2.80 +/- 0.13:1 (HCO3-:Na+). Possible functions of the glial cell Na+/HCO3- cotransporter, including the regulation of CO2 in the retina and the regulation of cerebral blood flow, are discussed. PMID- 1744700 TI - Myelin sheath survival following axonal degeneration in doubly myelinated nerve fibers. AB - Axonal contact plays a critical role in initiating myelin formation by Schwann cells. However, recent studies of "double myelination" have indicated that myelin maintenance continues in Schwann cells completely displaced from physical contact with the axon. This raises the possibility either that diffusible trophic factors are produced by the axon, or that the axon is not required for myelin maintenance by these displaced Schwann cells. To test these hypotheses, the axons involved in double myelination in the mouse superior cervical ganglion (SCG) were transected surgically by a transganglionic lesion. The inferior pole of the SCG was resected to limit axonal regeneration. This method produced a typical Wallerian pattern of degeneration in the superior pole, without compromising the blood supply or introducing nonspecific trauma. EM analysis at 1 and 5 d postoperatively showed that initially the axon degenerated, followed by breakdown of the inner myelin sheath. In those configurations where the outer Schwann cell was only partly displaced from the axon, the outer myelin sheath degenerated simultaneously. However, in completely displaced internodes the outer sheath survived degeneration of the axon and inner sheath. Outer internodes remained intact for at least 5 weeks after transection (the longest time point in this study), at which time they enclosed reorganized processes of the inner Schwann cells, their basal lamina, and numerous collagen fibrils. Axonal regeneration within surviving outer internodes was rare and was characterized by the development of typical Remak ensheathment by the inner Schwann cells. We conclude that in the mouse SCG, myelin maintenance does not depend on the continued presence of the axon. These data suggest further that myelin breakdown in Wallerian degeneration may be initiated by mechanisms other than absence of a viable axon. PMID- 1744701 TI - Contending with the elements. PMID- 1744702 TI - Seeking swifter approvals for new radioactive tracers. PMID- 1744704 TI - The development and application of mathematical models in nuclear medicine. PMID- 1744703 TI - Noninvasive quantification of hepatic arterial blood flow with nitrogen-13 ammonia and dynamic positron emission tomography. AB - To determine if dynamic PET and 13N-ammonia can be utilized to quantitate regional hepatic arterial blood flow (rHABF) noninvasively, eight anesthetized dogs and eight human volunteers were examined with PET following intravenous bolus administration of 13N-ammonia. Hepatic time-activity curves and the arterial input function were derived from ROIs drawn over the right lateral superior segment of the liver and the left ventricle of the heart, respectively. rHABF was quantitated using a two-compartment model, with comparison with simultaneously acquired microsphere blood flow measurement (MS) in the canine studies. rHABF derived from canine dynamic PET with 13N-ammonia were linearly related to microsphere values (rHABF = 0.92 x MS + 0.04, r = 0.98), with a mean of 0.40 ml/min/g. The results in eight normal volunteers gave a rHABF value of 0.26 +/- 0.07 ml/min/g. Dynamic 13N-ammonia hepatic PET allows noninvasive quantification of rHABF. PMID- 1744705 TI - Detection of infection in postoperative orthopedic patients with technetium-99m labeled monoclonal antibodies against granulocytes. AB - A prospective study of 106 orthopedic patients was performed for the detection of infection in the early postoperative stage using 99mTc-labeled murine Mabs directed against epitopes on granulocytes. Accuracy was 81% in the hips (n = 26), 81% in the thigh (n = 21), 84% in the knee (n = 19), and 100% in the tibia (n = 27). The technique did not work well in the spine where false-negative results were observed in the three patients studied. One patient suffered transient swelling of the eyelids following injection. Optimal imaging results were obtained 2-6 hr postinjection. PMID- 1744706 TI - Assessment of right ventricular overload by a thallium-201 SPECT study in children with congenital heart disease. AB - Thallium-201 planar and SPECT studies were performed in 38 children with congenital heart disease using high-resolution three-headed SPECT. The 201Tl total or average right ventricular-to-left ventricular (RV/LV) count ratios were measured by summed short-axis images. In the planar study, the RV/LV systolic pressure ratio correlated with 201Tl RV/LV average count ratio (r = 0.91) better than that in the SPECT study (r = 0.78). However, in the SPECT study, patients with atrial septal defect (n = 9), ventricular septal defect (n = 13), tetralogy of Fallot and double outlet right ventricle (n = 6) showed a characteristic distribution in the plot of RV/LV pressure ratio versus 201Tl RV/LV total count ratio. A prospective study showed that the RV/LV average count ratio was a good predictor of RV/LV pressure ratio (n = 19, r = 0.91). Three-headed SPECT is useful for pediatric cardiac studies, and the overload types found in congenital heart disease seemed to be differentiated by the SPECT study. PMID- 1744707 TI - Clinical evaluation of a scintigraphic method for diagnosing inflammations/infections using indium-111-labeled nonspecific human IgG. AB - This study was undertaken as part of a Phase II study to assess the sensitivity and safety of 111In-DTPA-human IgG, an imaging agent for the detection of inflammations and/or infections. Forty patients with infection/inflammation on the basis of clinical findings, microbiologic results, and/or the basis of results from other imaging modalities were studied. For evaluation of sensitivity, whole-body images were obtained at 6-12 hr (early) and 20-28 hr (delayed) postinjection and occasionally at 48 hr. No adverse reactions were recorded in any of the 40 patients studied. Positive results were obtained in 37 of 37 evaluable subjects (100%). The test appears to be a promising method for the detection of inflammation and/or infection. PMID- 1744708 TI - A quantitative model of technetium-99m-DTPA-galactosyl-HSA for the assessment of hepatic blood flow and hepatic binding receptor. AB - Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) was studied in normal volunteers and in patients with impaired liver function. The extrapolation approach originated the absolute dose of 99mTc-GSA in blood and the hepatic blood volume. The heart and liver regression curves were simultaneously fractionated into the three compartments (extrahepatic blood, hepatic blood and hepatocytes). Four differential equations were integrated with the six parameters as variables, and the smallest residual sum of squares was obtained by the damping Gauss-Newton method. The result of hepatic blood flow was 1603 +/- 144 (ml/min) in normal controls, which was compatible with previously reported values. Maximal removal rate (mg/min) showed statistically significant differences between the normal volunteers and patients with chronic hepatitis or liver cirrhosis. Our kinetic model of 99mTc-GSA can be used in the evaluation of liver function. PMID- 1744709 TI - The role of bone scintigraphy in the evaluation of talar dome fractures. AB - We undertook a retrospective study of 122 patients with ankle pain to determine the accuracy of bone scintigraphy using 99mTc-methylene diphosphonate (MDP) for detection of osteochondral talar dome fractures (OCTDF). Plain radiographs, which were available in 97 patients, had not revealed any abnormality in the talar dome. Bone scintigraphy was followed by CT, which was considered to be the reference test in diagnosing OCTDF. Analysis of our data showed that when the bone scan findings in the two highest confidence categories (high and moderate probability) were accepted as abnormal, the sensitivity and the specificity of the test were 0.94 and 0.76, respectively. Although CT is mandatory to establish the stage of OCTDF, it cannot be used routinely due to its high cost. Bone scintigraphy appears to be a good screening procedure that will identify patients who are likely to benefit from further radiographic studies such as CT. These findings are subject to further confirmation in a prospective study. PMID- 1744710 TI - Reference values for red cell survival times. AB - The first purpose of this investigation was to investigate in 35 young normal male subjects the use of the Dornhorst function and the weighted-mean method to calculate reference values for mean red cell survival time with and without correction for elution of 51Cr. We compared survival times calculated with the Dornhorst and weighted-mean methods with survival time estimated with linear or exponential models. Two methods to correct for elution of 51Cr from red cells were investigated. For the first method, correction factors were generated using the Dornhorst function fitted to mean survival curves obtained from the normal subjects. In the second method, the new Dornhorst rate constant method, the survival time, corrected for elution of 51Cr, was directly calculated from the experimental survival curve without applying correction factors. Correction for elution using the Dornhorst rate constant method was not successful and resulted in nonphysiologic values. The 95% confidence range of red cell survival time for reference subjects without correction for 51Cr elution was 37-74 days for the weighted-mean method and 37 to 73 days for the Dornhorst method. The 95% confidence range for normal subjects when the survival curves were corrected for elution was 47-179 days for the Dornhorst method and 58-161 days for the weighted mean method. The poor results obtained with the Dornhorst rate constant method and the large 95% confidence range were due to the rapid and large variation in elution rate of 51Cr from red cells. PMID- 1744711 TI - Significance of intensity of delayed activity during technetium-99m-RBC gastrointestinal bleeding study. AB - In 27 patients with normal hepatic function, delayed concentration of radioactivity (during 99mTc-RBC gastrointestinal bleeding studies) was compared with liver blood-pool activity. That is, for images at 4 to 24 hr postinjection, grading was accomplished by comparison to the liver blood pool (less than, equal to, or greater than hepatic activity). There was a correlation between the accuracy of scan interpretation (for active bleeding and localization) and the intensity of activity as related to the liver. This simple grading system may be useful for interpretation of delayed images during bleeding studies. PMID- 1744712 TI - Application of (methyl-11C)-methionine in the multicellular spheroid system. AB - Human glioma (U-343 MGa) and human colon carcinoma (HT-29) cell lines were cultured as multicellular spheroids, and the accumulations of the L- and D enantiomers of 11C-methionine were investigated. The accumulation of radioactivity in the spheroids was expressed as relative counts, by dividing the radioactivity measured in the spheroid with the radioactivity of the same volume of the incubation medium. The experiments were verified using 14C-labeled L- and D-methionine. The influence of spheroid volume, specific activity, incubation time, washing time, and the environmental temperatures were investigated. The spheroid model was used to determine the effect of the lipoxygenase inhibitors BW A4C and AA-861, the ether-phospholipid type PAF-antagonist CV-6209 and the protein synthesis inhibitor cycloheximide on methionine uptake. The results showed that 11C-L-methionine can be applied in the study of drug effects on multicellular tumor cell aggregates. PMID- 1744713 TI - Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. AB - No-carrier-added [18F]altanserin was synthesized by nucleophilic substitution of the corresponding nitro compound with [18F]fluoride in the presence of kryptofix 222 and K2CO3. After purification by preparative HPLC, [18F]altanserin was produced in less than 2 hr with a radiochemical yield of 10% (EOS) and a specific activity of 0.8-1.3 Ci/mumol. In rats, the tracer localized rapidly in the whole brain (0.5% ID/g organ) with a high binding to the frontal cortex. The frontal cortex/cerebellum ratio increased with time and reached a plateau of 11 at 2 hr postinjection. This uptake in S2 receptor regions was saturable and could be blocked by pretreatment with various S2 antagonists. This radiopharmaceutical appears to be more selective for S2 receptor sites than other ligands available today and allows the study of S2 receptors under in vivo conditions. PMID- 1744714 TI - Gallbladder visualization during post-therapy iodine-131 imaging of thyroid carcinoma. AB - A persistent, extra-thyroidal focus of 131I on whole-body imaging of thyroid carcinoma usually represents a functioning metastasis. We report a case of 131I localization within a septated gallbladder, initially mimicking an isolated hepatic metastasis. Adjunctive liver/spleen and hepatobiliary scintigraphy helped to elucidate the true nature of this 131I activity. PMID- 1744715 TI - Metastatic angiosarcoma with thrombocytopenia and intratumoral indium-111 platelet deposition. AB - A 66-yr-old woman with cutaneous angiosarcoma of the face presented with thrombocytopenia and metastases to the skeleton. Scintigraphic imaging with 111In oxine-labeled autologous platelets demonstrated localization of radiolabeled platelets at sites of metastatic tumor. This imaging study suggests intratumoral destruction of platelets by the metastases of the malignant vascular tumor as the cause of the patient's thrombocytopenia. PMID- 1744716 TI - Localization of recurrent medullary thyroid carcinoma with technetium-99m methoxyisobutylnitrile scintigraphy: a case report. AB - This case report demonstrates the successful localization of metastatic medullary thyroid carcinoma with 99mTc-labeled methoxyisobutylnitrile (MIBI). Disease recurrence was initially localized using 201Tl and by immunoscintigraphy with 111In-labeled anti-carcinoembryonic antigen (anti-CEA) antibody fragments. Scintigraphy with 99mTc-MIBI yielded higher target-to-background ratios than 201Tl or 111In-anti-CEA. Technetium-99m-MIBI may be a useful agent in the localization of recurrent medullary thyroid carcinoma. PMID- 1744717 TI - Thallium-201 SPECT depicts radiologically occult lung cancer. AB - A case of radiologically occult lung cancer is presented in which 201TI SPECT of the chest clearly delineated the involved area. A 66-yr-old man underwent chest screening examinations for asymptomatic smokers and presented a positive sputum cytology for lung cancer. Conventional chest x-ray, tomography of computed radiography, and a CT scan failed to locate the lesion in the lung. Thallium-201 SPECT, however, was successful in depicting the area of the involvement. PMID- 1744718 TI - Residual spleen found on denatured red blood cell scan following negative colloid scans. AB - The technetium-sulfur colloid liver-spleen examination is widely used to evaluate patients with idiopathic thrombocytopenic purpura for residual splenic tissue following splenectomy. Technetium-labeled heat-damaged red blood cell imaging is another sensitive test for residual splenic tissue. We recently encountered a patient with idiopathic thrombocytopenic purpura who was initially evaluated with a technetium sulfur colloid scan which was negative. A denatured red blood cell scan was subsequently performed which revealed intense focal activity in the region of the splenic bed. Surgery confirmed this to be splenic tissue. Our results emphasize the utility of the denatured red blood cell examination in the setting of strong clinical suspicion for residual splenic tissue following a negative sulfur colloid study. PMID- 1744719 TI - Cellular basis for the elevated gallium-67 computed lung index in a rheumatoid lung patient. AB - A patient with high levels of serum rheumatoid factor and an open lung biopsy which showed high-grade interstitial pneumonia with large numbers of lymphocytes and plasmocytes had intense gallium uptake in the lungs. Lymphocytes and/or plasmocytes might be responsible for the gallium uptake even though neutrophils are usually credited with high-level uptake. Differential cell counts demonstrated plasmocyte and lymphocyte preponderance, but neutrophil paucity. In vitro cell cultures of purified neutrophils, monocytes, leukemic plasmocytes, and resting and stimulated lymphocytes with 67Ga showed that plasmocytes take up comparatively low levels of 67Ga, but that activated lymphocytes take up levels that approach neutrophils. It is probable that both rheumatoid lung plasmocytes and activated lymphocytes are responsible for the pulmonary 67Ga concentration in this patient. PMID- 1744720 TI - Myocardial accumulation of monoclonal antimyosin Fab in hypertrophic cardiomyopathy and postpartum cardiomyopathy. AB - Indium-111-antimyosin Fab scan was performed in patients with hypertrophic and postpartum cardiomyopathies to assess whether or not myocardial damage can be delineated. In two patients with hypertrophic cardiomyopathy, intense and diffuse antimyosin uptake was observed, although there was no evidence of acute myocardial damage or wall motion abnormality. A patient with postpartum cardiomyopathy showed a dense and relatively localized accumulation in the left ventricular anterior wall in association with thallium perfusion and wall motion abnormalities. Thus, antimyosin scanning can delineate not only manifested but also subclinical myocardial damage in hypertrophic and postpartum cardiomyopathies which may not be detectable by other techniques. PMID- 1744721 TI - Reference range determination: the problem of small sample sizes. AB - The process of developing and validating a quantitative test includes determination of a reference range. Traditionally this has been taken as the mean +/- 2 standard deviations for a random sampling from a reference population. However, this method fails to recognize the substantial variability in the sample mean and standard deviation for the small sample sizes frequently encountered in nuclear medicine. A new approach, which involves calculating confidence intervals for the upper and lower bounds of the traditionally defined range, recognizes three ranges of values: normal, indeterminate, and abnormal. The principles of this approach are illustrated using differential renal function in twelve renal transplant donors. The 99mTc-DTPA differential uptake between 1 and 2 min gave a traditionally-defined single-kidney range of 50% +/- 8%, whereas with our method the normal range would be 50% +/- 6% with indeterminate ranges of 37%-44% and 56% 63%. These values are consistent with the wide variation in reference ranges reported in the literature, and suggest that much of this variability may be a statistical artifact resulting from inadequate sample sizes. A nomogram has been derived that permits the power of the reference range determination to be easily calculated from the sample size. Analysis of the effect of sample size on the accuracy of the upper and lower bounds of the reference range is advocated whenever small reference populations are used. PMID- 1744722 TI - Biological background subtraction improves immunoscintigraphy by subsequent injection of antigen. AB - We have developed an 111In-labeled antibody for in vivo use directed against tissue plasminogen activator demonstrating focal fibrinolytic activity. However, a major problem in immunoscintigraphy is the low signal-to-noise ratio due to circulating antibody. The hepatic clearance of t-PA is very rapid. The effect of a subsequent injection of a small amount of t-PA shortly after the antibody administration to increase the blood clearance rate of the formed antigen antibody complexes was examined in six rabbits. More than 99% of the circulating antigen-antibody complexes were eliminated by the liver within 10 min. This technique could make immunoscintigraphy a first line diagnostic tool in acute medicine including imaging of thromboembolic lesions in organs with high blood volumes such as the lungs, the heart, and the brain. PMID- 1744723 TI - Immunoscintigraphy of thrombi. PMID- 1744724 TI - Diagnostic accuracy and deep venous thrombosis: a biostatistician's perspective. PMID- 1744725 TI - The art of bone scintigraphy--technical aspects. PMID- 1744726 TI - Performance standards in positron emission tomography. AB - A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction. PMID- 1744727 TI - Clinical PET--a modest proposal. PMID- 1744728 TI - Assessment of myocardial infarction with three radiotracers. PMID- 1744729 TI - Development of new radiopharmaceuticals. PMID- 1744730 TI - The nurse executive and the governing body. Synergy for a new era. AB - Nurse executives play a vital role in the overall governance of healthcare organizations, and many participate on governing boards. However, we lack a model for effective governing-body relations and contributions. The author presents major functions of the governing body with emphasis on the critical elements provided by the nurse executive. The author also defines major outcomes for nursing. PMID- 1744731 TI - Implementing an ethics committee in rural institutions. AB - Ethical conflicts occur in rural as well as in urban healthcare institutions. One means of addressing these complex issues is through interdisciplinary discussions by a bioethics committee. There are, however, social, economic, geographic, and demographic variations unique to both environments that can impact ethical issues, and these must be addressed when such a committee is implemented in either setting. The authors describe the rural variations and the implications for nurse administrators who often assume an active role in planning and organizing bioethics committees. PMID- 1744732 TI - Work redesign in high-intensity environments. ProACT for critical care. AB - Hospitals are becoming immense intensive care units despite a continuing shortage of critical care nurses. While there has been widespread application of work redesign concepts in nursing during the last several years, few projects involving critical care have been reported. The authors describe a comprehensive restructuring initiative in the critical care setting and focus on the administrative implications of this work. PMID- 1744733 TI - Feeding the homeless. AB - Nurses have a unique role in addressing homelessness, an issue of vital national concern. The management and organizational expertise of nurses can be key elements to coordinating community resources to assist the homeless. The authors describe the design and implementation of a community meal program for the homeless. PMID- 1744734 TI - Designing an internal organizational merger. AB - Healthcare managers face problems resulting from restructuring and downsizing activities meant to increase operational efficiency and reduce costs. Although keys to the success of multiorganizational mergers are well documented, directives for managing internal mergers are less clearly stated. The authors discuss a five-step plan designed to facilitate an internal merger through the strategic coordination of stakeholders. PMID- 1744736 TI - Healthy People 2000: challenges and opportunities. PMID- 1744735 TI - Maximizing market potential in home care. AB - National trends in demographics and skyrocketing healthcare costs are escalating the demand for home healthcare. As a result, competition for a share of the home care dollar has become fierce. In the next decade, home care providers- hospitals, proprietary companies, and nonprofit agencies--will be competing for a portion of the projected $60 billion in home care earnings. The author offers three recommendations to providers who wish to ensure survival and growth in these fast-moving times. PMID- 1744737 TI - Planning the interview for a clinical nurse researcher. AB - The number of clinical nurse researcher positions seems to be increasing in healthcare agencies today. There are some unique features of the clinical nurse researcher role, including the complexities of a research position, the relatively recent introduction of the role in some clinical settings, and the frequency with which the position is coupled with other major clinical, administrative, or educational responsibilities. To increase the effectiveness of both the chief nurse executive and the clinical nurse researcher during the employment interview, the authors discuss five lines of inquiry that the interviewer or candidate can use. PMID- 1744738 TI - Administrative prosperity: principle IV, staying renewed in your career. PMID- 1744739 TI - Atopic status as a factor in job decision making in grain workers. AB - We conducted allergy skin-prick testing on 207 young cereal grain workers within 0.27 years of the commencement of their employment in the grain industry and again after 1.34 years of employment on 124 workers. We also studied 120 control subjects on the first observation and 105 on the second observation. Grain workers had lower prevalence than did the controls of positive skin tests on the first observation, and this difference increased by the second observation. Respiratory symptoms were more frequent among grain workers with positive skin tests who dropped out of the industry than among those who stayed in the industry. We conclude that atopic status may be a factor in job selection and drop out decision making and may be a factor explaining the healthy worker effect. PMID- 1744740 TI - The inefficiency of surgical masks for protection against droplet nuclei tuberculosis. PMID- 1744742 TI - In defense of TLVs. PMID- 1744741 TI - Brain cancer and exposure to electromagnetic fields. PMID- 1744743 TI - Advances in cancer biomarkers as applied to chemical exposures: the ras oncogene and p21 protein and pulmonary carcinogenesis. AB - Pulmonary carcinogenesis due to occupational and environmental exposures to chemical carcinogens such as polycyclic aromatic hydrocarbons presents an interesting model for study of possible oncogene-related cancer biomarkers. Polycyclic aromatic hydrocarbons are important respiratory carcinogens and have been shown to cause specific mutational lesions that can lead to the activation of the ras oncogene and expression of its p21 protein product; ras oncogene activation and p21 expression frequently are detected in human lung cancers. In addition, the p21 protein is detectable via immunoblotting techniques in the serum of lung cancer patients and in selected persons in exposed worker cohorts at risk for the development of lung cancer. Thus, the ras oncogene and p21 protein may be useful biomarkers for monitoring pulmonary carcinogenesis in exposed populations. PMID- 1744744 TI - Lung cancer and hydrogen chloride exposure: results from a nested case-control study of chemical workers. AB - There are few epidemiologic data available to address the question of potential carcinogenic effects of hydrogen chloride (HCl) exposure on humans. An opportunity arose to augment a nominal HCl exposure classification that had been done earlier for a nested case-control study of lung cancer among a cohort of chemical manufacturing employees. Working from first-hand knowledge of the relevant chemical processes and limited HCl monitoring data, a certified industrial hygienist estimated average exposures for each of the job assignments of 308 lung cancer cases and 616 comparison workers. The risk of lung cancer was then analyzed in relation to several measures of HCl exposure, including duration, a cumulative exposure score, highest average exposure, and latency. None showed evidence of an association between HCl exposure and lung cancer. This is consistent with the limited rodent bioassay data, which also failed to find a tumorigenic response from HCl. Thus, even at high level occupational exposures (up to 3000 micrograms/m3 for several years) there is no evidence that HCl is a human carcinogen. PMID- 1744745 TI - The cost-effectiveness of work-site wellness programs for hypertension control, weight loss, and smoking cessation. AB - The cost-effectiveness of work-site wellness programs for reducing cardiovascular disease risks of employees was examined at three manufacturing plants. A fourth plant was used as a control site to estimate levels of risk reduction achieved from wellness screening and preexisting services, without further interventions. The cardiovascular disease risks included in the study were hypertension, obesity, and cigarette smoking. The annual direct cost per employee for postscreening interventions was $2.97 for site 1 (control site), $17.68 for site 2 (health education), $30.96 for site 3 (health education plus follow-up counseling), and $38.31 for site 4 (health education, follow-up counseling plus plant organization for health promotion). Of the three experimental sites, sites 3 and 4 were more effective and more cost-effective than was site 2, both in terms of engaging employees at risk of cardiovascular disease into treatment or program participation and of reducing their risks or preventing relapse. For engaging employees into treatment/program participation, sites 3 and 4 were nine to ten times more cost-effective than was site 2; for reducing risks/preventing relapse, sites 3 and 4 were five to six times more cost-effective than was site 2. At sites 3 and 4, the total direct cost per percent of risks reduced/relapse prevented was less than one dollar ($.67 and $.74, respectively) per employee per year. Program costs may vary considerably across companies because of differences in salary structures and overhead costs. These are held constant in this report for comparison across program models. PMID- 1744746 TI - Introducing management skills and issues in preventive medicine residency programs: a survey. AB - A questionnaire survey of 60 accredited preventive medicine residency programs was conducted to determine the percentage of programs in which management training is undertaken and to identify the nature of such training. Forty eight of the 60 programs (80%) returned a completed questionnaire. Forty three of the 48 programs responding (90%) state that the teaching of management skills is a defined goal of their program. Ninety percent introduce management skills in the practicum year in an administration rotation or by providing opportunities to practice management skills in other rotations. Thirty five (73%) of responding programs present didactic sessions containing a focus on management issues, and academic year courses contain a focus on management skills or issues in 46 (96%). Considering the need for management training in preventive medicine careers, we are encouraged by these figures. However, although this survey determined the extent to which management training is undertaken and the reported content thereof, it did not attempt to evaluate the depth or effectiveness of this training. Therefore, we must continue to emphasize a longitudinal and multidimensional approach to management training during the residency years. PMID- 1744747 TI - Work-site smoking policies in small businesses. AB - A growing number of workers in the United States are employed in small businesses. This study describes the experiences of small work sites in implementing policies restricting smoking. In the fall of 1987, we surveyed by telephone 216 work sites employing 120 or fewer persons. Compared with companies without policies, companies with policies were larger and reported having fewer smokers and more management support for smoking policies. Seventy-three percent of work sites without a smoking policy said they would be very likely to implement a policy if it were required by law; 42% of work sites with a policy reported offering smoking cessation assistance to their employees. Overall satisfaction and compliance with the smoking policy was high among work sites with a policy. The findings of this study have key implications for other small businesses considering implementing a smoking policy. PMID- 1744748 TI - Utilization of preventive health services by an employed population. AB - To determine the utilization rates of selected preventive services in an employed population, we analyzed the responses of 18,053 health profile participants. Overall utilization rates for preventive services were high: 86.0% of respondents had their blood pressure checked, 94.0% of all women had a Pap smear and 81.3% had clinical breast examinations, 42.4% of respondents aged 40 and older had a rectal examination and 31.8% of those aged 50 and older had a test for occult blood in the stool, and 33.7% had a routine sigmoidoscopy. With the exception of blood pressure screening, the percentage of our respondents utilizing preventive services was considerably higher than the corresponding percentages in the US population as reported in the National Health Interview Survey. Nevertheless, the results suggest substantial opportunity for employers to encourage the appropriate use of preventive health services among employees. PMID- 1744749 TI - Work stress in emergency medical technicians. AB - To better understand the dynamics underlying their high turnover rate, emergency medical technicians (EMTs) were asked to participate in a union-sponsored study. Fifty-two percent of 200 EMT union members returned the three mailed questionnaires: the Occupational Stress Index, which assesses stress, strain, and coping; the Staff Burnout Scale for Health Professionals; and a survey that probed areas of job satisfaction. The sample had high stress, strain, and burnout scores. Coping skills were within the normal range. Burnout, stress, strain, and coping (BSS&C) were significantly related to job satisfaction, worry about infectious diseases, and perceptions of being poorly treated by emergency room personnel and fire fighters. BSS&C also were related to being upset by "runs" related to injuries from violence, drug overdoses, and exposure. Job dissatisfaction was related to attitudes that the job adversely affects one's family, that the EMT quarters are uncomfortable, and that administrators are not knowledgeable of the job demands and skills of EMTs. Areas of great discontent were the low salary of the profession and the inadequacy of the equipment. PMID- 1744750 TI - The positive known association design: a quality assurance method for occupational health surveillance data. AB - Quality control must be an integral component of an occupational health surveillance program. The positive known association design offers the occupational health physician a method to test, on a population basis (ie, high periodic medical surveillance examination participation rates by the employees), the quality of periodic medical surveillance data. Several well-established biological associations were evaluated and observed in this study, including a dramatic relation between white blood cell counts and smoking. We highly recommend that the positive known association design be incorporated in the quality assurance procedures of occupational health surveillance programs. PMID- 1744751 TI - Factors predicting readmission of older general medicine patients. AB - OBJECTIVES: 1) Identify demographic, clinical social support, functional, and psychological factors about which data are available within 24 hours of hospital admission associated with emergent unscheduled readmission for a group of older general medicine patients; 2) develop a model to predict emergent readmission. DESIGN: Interview- and chart-based study of emergent admissions that occurred within 60 days of discharge. SETTING: General medicine wards of the Memphis Veterans Affairs Medical Center, an 862-bed university-affiliated tertiary care facility. PATIENTS/PARTICIPANTS: General medicine patients greater than or equal to 65 years old (n = 173). Inclusion criteria were willingness to participate, written consent (patient or family member), and patient interview within 36 hours of admission. MEASUREMENTS AND MAIN RESULTS: The dependent variable was emergent readmission within 60 days of discharge from the hospital. Independent variables included demographic (age, race, income, education), social support (marital status, living arrangements), psychological (cognition, depression), activities of daily living functioning, and clinical (diagnoses, type and source of admission, length of stay, numbers of hospitalizations and days of hospitalizations in the past year, illness severity) parameters. Readmitted patients were emergently admitted and more severely ill, had more diagnoses of chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF), less ischemic heart disease, and more hospitalizations and hospital days in the past year (all p less than 0.05). Logistic regression identified diagnostic group (COPD or CHF), emergent admission, and admission severity of illness as predictive of readmission. The likelihood of being readmitted was 5.4. Accuracy of the three-variable model was 76%, predicted value positive, 73%, and predictive value negative, 77%. CONCLUSIONS: Chronically ill patients who are severely ill at index admission and who have had several hospitalizations in the past year tend to be readmitted. Using this model, high-risk patients may be prospectively targeted to reduce readmissions. PMID- 1744752 TI - Predicting the need for hospitalization of ambulatory patients with pneumonia. AB - OBJECTIVE: To develop clinical guidelines to identify patients with pneumonia who might be safely treated as outpatients. DESIGN: Retrospective chart review to derive guidelines, with subsequent prospective validation. SETTING: Initial review completed for patients seen in the emergency room (ER) of a university hospital and a community-based internal medicine practice. Validation conducted in the ERs of a university hospital and a community teaching hospital. PATIENTS/PARTICIPANTS: Individuals aged 16 years and older presenting with newly diagnosed pneumonia. Follow-up obtained through mail or telephone contact and chart review. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the initial retrospective review, 141 pneumonia patients without obvious reasons for hospital admission were identified and then classified as hospitalization necessary or unnecessary. Of these patients, 33 were classified as requiring admission. Multivariate analysis identified five variables that differentiated low-risk from high-risk study patients. These variables (and their relative weights) were: serious comorbid illness (3 points); preexisting lung disease (2 points); multilobar lung involvement by the disease by chest x-ray (2 points); observed or likely aspiration (2 points); and symptom duration of less than 7 or greater than 28 days (1 point). Risk scores were calculated using these variables. Patients with low scores (0-2 points) rarely had complications, and only one of 53 such patients (2%) was judged to require hospitalization. In contrast, patients with high scores (greater than or equal to 6 points) had frequent complications and 20 of 29 (69%) were felt to need hospitalization. Similar results were found during the validation phase. CONCLUSIONS: Clinical findings appear to help distinguish patients who need admission for treatment of pneumonia from those who do not. If validated in other settings, the clinical utility of these guidelines in assisting decision making about hospitalization should be determined. PMID- 1744753 TI - The cost and effectiveness of an education program for adults who have asthma. AB - STUDY OBJECTIVE: To determine whether a self-management training program decreases emergency department visits and reduces costs for patients with asthma. DESIGN: Randomized controlled trial of an educational program. SETTING: Two sites -an urban emergency room and a suburban emergency room. PATIENTS: 241 asthma patients between the ages of 18 and 70 years. Of the 119 patients in the intervention group and the 122 in the control group, 185 (76%) were available for follow-up. INTERVENTION: All patients seen in the emergency departments were given usual medical care and follow-up. Patients in the intervention group were asked to attend three educational sessions on asthma conducted by a specially trained RN. The program stressed importance of medication compliance, methods to control and prevent attacks, effects of drugs and rationale for their use, relaxation exercises, and smoking cessation. MEASUREMENT AND MAIN RESULTS: All patients received telephone interviews four, eight, and 12 months after entry into the study. Reports based on hospital admissions and emergency room utilization were verified by billing records. Three patients died during the study, none from asthma-related problems. The intervention group had significantly fewer asthma-related emergency visits (16 visits per 100 persons) than did the control group (39 per 100 persons); p = 0.0005 for the 12 months of follow-up. The effect of the intervention on asthma-related emergency department visits was strongest during the initial four months postintervention (68 per 100 persons versus 220 per 100 persons, p = 0.003). The financial analysis showed that the $85/person cost for the educational sessions was offset by the $628/person reduction in emergency room charges. CONCLUSION: Education enables patients with asthma to decrease utilization of emergency services. PMID- 1744754 TI - Seizure vs. syncope: measuring serum creatine kinase in the emergency department. AB - OBJECTIVE: To determine the utility of serum creatine kinase measurement for diagnosing generalized tonic-clonic seizures in patients presenting to an emergency department with transient loss of consciousness. DESIGN: Prospective evaluation of a diagnostic parameter. Retrospective data collection with blinded assignment to diagnostic groups. SETTING: University teaching hospital. PATIENTS: Sequential sample of 205 patients with transient loss of consciousness. The study group consisted of 96 patients who had creatine kinase measurements in the emergency department. MEASUREMENTS AND MAIN RESULTS: An investigator blinded to the results of creatine kinase measurements retrospectively classified events into seizure and nonseizure groups on the basis of clinical presentation, prior history, and follow-up investigations. Mean (+/- SE) creatine kinase level was significantly higher in the seizure group (231.1 +/- 34.8 U/L vs. 70.5 +/- 5.6 U/L, p less than 0.001). Elevated creatine kinase had a test specificity of 0.98 (95% CI 0.90-1.00) and a sensitivity of 0.43 (95% CI 0.28-0.59). The discriminating power of creatine kinase elevation was directly related to the time interval between the event and testing (p less than 0.0001). Among samples taken more than three hours after the event, test sensitivity was 0.80 (0.52 1.00) and specificity was 0.94 (0.71-1.00). CONCLUSION: Creatine kinase may be a useful test for evaluating patients with transient loss of consciousness. The test is highly specific for diagnosing generalized seizures in the emergency department. Test sensitivity improves by sampling serum at least three hours after the event. PMID- 1744755 TI - Hypochondriacal patients, their physicians, and their medical care. AB - OBJECTIVE: To examine the views hypochondriacal patients have of their physicians, and their physicians' assessments of the hypochondriacal patients. DESIGN: A sample of patients meeting DSM-III-R diagnostic criteria for hypochondriasis was obtained by screening consecutive medical outpatients. They underwent a battery of self-report questionnaires and structured interviews, their medical records were audited, and their physicians completed questionnaires about them. A random sample of nonhypochondriacal patients from the same clinic served as a comparison group. SETTING: A large general medicine outpatient clinic of an academic teaching hospital. PATIENTS: 41 DSM-III-R hypochondriacs and 71 comparison patients. MEASUREMENTS AND MAIN RESULTS: Hypochondriacal patients were more dissatisfied with their physicians than were comparison patients. Physicians rated the hypochondriacal patients as more frustrating to care for, more help rejecting, and more demanding. Physician ratings of how hypochondriacal their patients were correlated significantly with their ratings of how frustrating they considered the patients (R2 = 0.36) and with objective measures of how hypochondriacal the patients were (incremental R2 = 0.08). Physician estimates of anxiety and depression in the hypochondriacal patients were not statistically related to patient anxiety and depression. In contrast, physician estimates of patient anxiety and depression were significantly associated with the presence of anxiety and depression in comparison patients. CONCLUSIONS: The physician's use of the term hypochondriasis is closely associated with his or her frustration with the patient and is associated with objective measures of the extent of hypochondriacal symptoms. In addition, the presence of DSM-III-R hypochondriasis impairs the physician's accuracy in assessing the levels of the patient's anxiety and depression. PMID- 1744756 TI - Sympathy, empathy, and physician resource utilization. AB - OBJECTIVE: To test the hypothesis that physicians preferring a sympathetic over an empathetic response to a hypothetical patient's misfortune will utilize more health care resources in the care of their patients. DESIGN: Physicians were asked to select either the sympathetic response or the empathetic response to a hypothetical patient's misfortune (death of a spouse) and to state their preferences for intubation of a hypothetical end-stage lung-disease patient. For each physician, hospital records were retrospectively reviewed to assess the mean number of laboratory tests ordered per clinic patient and the mean duration of cardiopulmonary resuscitations he or she performed before declaring his or her efforts unsuccessful. SETTING: General medicine clinic at a large urban hospital. PARTICIPANTS: 101 physicians above the postgraduate year-I level who attended the general medicine clinic. MEASUREMENTS AND MAIN RESULTS: As hypothesized, physicians selecting the sympathetic option (n = 58) had a greater mean preference for intubation (p less than 0.02), ordered more laboratory tests per patient in clinic (p less than 0.03), and performed cardiopulmonary resuscitation for longer periods of time before declaring their efforts unsuccessful (p less than 0.06) than did physicians selecting the empathetic option (n = 38). CONCLUSIONS: These data suggest that the constructs of sympathy and empathy reflect psychological aspects of physicians that have a measurable influence on their practice behaviors. PMID- 1744757 TI - Physicians' and nurses' perceptions of ethics problems on general medical services. AB - OBJECTIVE: To understand the kinds of clinical situations physicians and nurses regard as "ethics problems." DESIGN: The authors prospectively studied physicians' and nurses' perceptions of ethics problems using paired interviews. Individual interviews were conducted with physicians and nurses as they cared for the same patients during a six-week period. Each was asked whether any ethics problems had arisen in the care of his or her patients and, if so, to give a brief description of each problem. SETTING: Three general medical services in a 497-bed community teaching hospital. PARTICIPANTS: 13 physicians (mostly family medicine residents) and 42 nurses caring for 142 patients. MAIN RESULTS: The physicians and nurses thought ethics problems were present in 75 of the 142 patients cases. Physicians and nurses identified ethics problems with similar frequencies; however, they often identified ethics problems in different patient cases or identified different ethics problems in the same case. Physicians and nurses described a variety of problem types. Physicians identified more problems related to quality of life, inappropriate hospital admissions, and cost of care; nurses identified more problems related to patient preferences, family wishes, pain management, implementing treatments, and discharge planning. A fourth of the ethics problems identified by physicians and nurses involved interstaff conflicts. CONCLUSIONS: The physicians and nurses studied considered a broad range of clinical situations to be "ethics problems," and they perceived them to occur frequently. Systematic differences were found between physicians' and nurses' perceptions of ethics problems, and many ethics problems generated interstaff conflicts. Incorporating this kind of information into clinical ethics education programs, and into hospital policies, may represent a useful approach toward improving physician-nurse interaction. PMID- 1744758 TI - Practical problems of conducting patient-satisfaction surveys. AB - OBJECTIVE: Patient-satisfaction surveys have been used frequently to assess the humanistic behaviors and skills of internal medicine housestaff. In conducting their first such survey, the authors found that many practical problems affected the progress and outcome of the project. This discussion of the authors' experiences is intended to be helpful to others considering patient-satisfaction surveys as part of their housestaff-evaluation process. DESIGN: A description of the practical aspects of conducting a patient-satisfaction survey as well as the problems that the authors encountered. SETTING: Both inpatient and outpatient settings at a major university internal medicine residency program. PATIENTS/PARTICIPANTS: Ambulatory and hospitalized patients under the care of categorical internal medicine interns were eligible for participation in the study. INTERVENTIONS: An established, validated patient-satisfaction questionnaire with high reported reliability was given to patients. MEASUREMENTS AND MAIN RESULTS: Although well over 90% of patients were willing to participate, 10% of participating outpatients and 16% of participating hospital patients could not provide a usable patient-satisfaction questionnaire even with assistance. Certain patient characteristics were responsible for these decreased completion rates. Among the hospitalized patients, 42% of all eligible patients were either too ill or too cognitively impaired to even be approached for participation in the study. CONCLUSIONS: Patient-satisfaction surveys are labor-intensive, require significant resources, and are temporally demanding. Results from them must be viewed with certain caveats. PMID- 1744759 TI - Gastroenterology consultations from the internal medicine physician's perspective. AB - OBJECTIVE: To examine the patterns of use of gastroenterology consultations by internal medicine physicians. DESIGN: A survey of licensed physicians in the three metropolitan areas in Arizona where gastroenterologists are available. The physicians were asked how likely they were to obtain gastroenterology consultations for a variety of different gastrointestinal illnesses. Comparisons between groups were done with chi-square analysis. MEASUREMENTS AND MAIN RESULTS: Forty-six percent of the physicians responded. The majority of respondents believed that esophagogastroduodenoscopy and colonoscopy should be available without gastroenterology consultation (65% and 64%, respectively). Physicians in practice more than ten years were less prone to request consultation for gastrointestinal complaints that were likely to result in endoscopic procedures, such as the diagnosis of peptic ulcer disease or inflammatory bowel disease, or guaiac-positive stool. Internal medicine residents were more likely to seek consultations for both endoscopic and cognitive gastrointestinal complaints. Internal medicine residents were far more likely to request gastroenterology consultations for most patients with upper-gastrointestinal-tract bleeding (91% vs. 60%, p less than 0.001) and lower-gastrointestinal-tract bleeding (65% vs. 22%, p less than 0.0001) than were internists practicing more than ten years. CONCLUSIONS: The majority of internal medicine physicians would like to order endoscopic procedures without gastroenterology consultations, much as they order radiography. Recently trained physicians are far more likely to request consultants for procedure-related problems. PMID- 1744760 TI - Do resident and staff physicians differ in the types and costs of antihypertensive drugs they select? AB - OBJECTIVE: To compare the types and costs of drugs prescribed by resident and staff physicians treating patients with uncomplicated essential hypertension. DESIGN: Cross-sectional study, using a computer-based medical record database. SETTING: Primary care internal medicine clinic in a large teaching hospital. PATIENTS/PARTICIPANTS: Hypertensive patients seen by ten postgraduate year-1 (PGY 1) and PGY-2 primary care internal medicine residents and four staff physicians practicing in the same clinic. MEASUREMENTS AND MAIN RESULTS: The types and costs of antihypertensive drugs prescribed for the patients treated by resident and staff physicians were compared. A larger proportion of patients of resident physicians than of staff physicians were treated with calcium channel blockers [19(15%) vs. 40(4%), p less than 0.001]; residents prescribed thiazide diuretics less frequently and beta-blockers more frequently than did staff physicians, although these differences were not significant. The estimated average wholesale price of antihypertensive drugs for patients cared for by residents was 35% higher than that for patients cared for by staff physicians ($0.73 vs. $0.54, p = 0.048). This difference was not fully explained by differences in practice composition. CONCLUSIONS: Resident physicians in this study selected more expensive medications to treat hypertension than did their faculty preceptors, even when differences in practice composition were considered. PMID- 1744761 TI - The impact of the night float system on internal medicine residency programs. AB - OBJECTIVE: To study the design, method of implementation, perceived benefits, and problems associated with a night float system. DESIGN: Self-administered questionnaire completed by program directors, which included both structured and open-ended questions. The answers reflect resident and student opinions as well as those of the program directors, since program directors regularly obtain feedback from these groups. SETTING/PARTICIPANTS: The 442 accredited internal medicine residency programs listed in the 1988-89 Directory of Graduate Medical Education Programs. RESULTS: Of the 442 programs, 79% responded, and 30% had experience with a night float system. The most frequent methods for initiating a night float system included: decreasing elective time (42.3%), hiring more residents (26.9%), creating a non-teaching service (12.5%), and reallocating housestaff time (9.6%). Positive effects cited include decreased fatigue, improved housestaff morale, improved recruiting, and better attitude toward internal medicine training. The quality of medical care was considered the same or better by most programs using it. The most commonly cited problems were decreased continuity of care, inadequate teaching of the night float team, and miscommunication. CONCLUSION: Residency programs using a night float system usually observe a positive effect on housestaff morale, recruitment, and working hours and no detrimental effect on the quality of patient care. Miscommunication and inadequate learning experience for the night float team are important potential problems. This survey suggests that the night float represents one solution to reducing resident working hours. PMID- 1744762 TI - Integrating occupational health into the medicine clerkship using problem-based learning. AB - OBJECTIVE: To improve medical students' ability and willingness to obtain occupational histories from their patients. PARTICIPANTS: General medicine faculty and internal medicine teaching residents, who participated as instructors, and medical students during their required internal medicine clerkships. SETTING: The primary teaching hospitals of two medical schools. DESIGN: During alternate months, students participated in problem-based sessions that included occupational health objectives (intervention) or attended the standard small-group didactic sessions (control). Process evaluations were collected from students and faculty in the intervention group following each session. Outcome evaluation was performed using chart audit and multiple-choice testing to compare the intervention and control groups. INTERVENTION: Intervention students participated in at least one problem-based session incorporating occupational aspects of disease into clinical internal medicine. Instructors received information packets and materials but had no other expertise in occupational medicine. MEASUREMENTS AND MAIN RESULTS: The great majority of ratings on the process evaluations showed that the students were "moderately" to "extremely" interested in the session attended. No student rated any session to be a "waste of time," and over 90% of students would recommend the session being evaluated to a friend. Chart audit showed that students in the intervention group recorded slightly more occupational information than did those in the control group (an average of 2.97 vs. 2.37 pieces of information, p = 0.06). When the most commonly documented data (employment status and job title) were ignored, the difference between group means (1.1 vs. 0.91) was significant (p = 0.03), suggesting that intervention students were more likely to probe further into a patient's occupational history. Both groups of students collected less occupational information from women than from men (t = 3.22, p = 0.0035). Multiple-choice tests revealed no difference between the two groups in overall medical knowledge or occupational medicine knowledge. CONCLUSIONS: Problem-based learning with specific occupational content is well accepted by students and modestly improves their occupational history taking. PMID- 1744763 TI - Casemix in an internal medicine clerkship: educational value of the clinical problems seen. AB - OBJECTIVE: To evaluate the casemix seen during an internal medicine clerkship and to assess the educational value of the problems seen. DESIGN: A modified Delphi group opinion technique was used to develop a clerk log that included priority problems for internal medicine. Over a 12-month period, clerks recorded their exposure to the problems seen during their eight-week rotations. General internists rated the importance of each of the problems on a three-point scale. SETTING: The inpatient internal medicine services in six university teaching hospitals. SUBJECTS: All clinical clerks in a single undergraduate year recorded their experiences. All university-based general internists participated in rating problem importance. MEASUREMENTS AND MAIN RESULTS: The final approved log contained 72 problems, 64 of which received importance ratings greater than or equal to 2 on the three-point scale. The frequency of clerk exposure per problem was high and the correlation between frequency of exposure and importance was good. Ten important problems had relatively low exposure and four problems of lower importance had high exposure. CONCLUSIONS: The clinical clerks were exposed to a broad spectrum of diseases, but some key problems were not well represented on the wards. Alternative strategies, including increased ambulatory care exposure, will be required to complete the exposure and to assure that the quality of patient exposure matches the quantity. PMID- 1744764 TI - Fellowship training in academic general internal medicine: a curriculum survey. AB - OBJECTIVE: To determine whether current fellowships in general internal medicine (FGIM) meet the perceived needs and objectives of physicians entering careers in academic internal medicine. DESIGN: A modified Delphi method yielded the 18 curricular elements included in the mailed survey. Participants outlined both actual and ideal fellowship experiences by rating the degree of emphasis of each curricular element on a Likert scale. Respondents then prioritized elements by rank-ordering them on perceived importance. Current job descriptions and opinions on related issues in FGIM were collected. PARTICIPANTS: Potential fellows, current fellows, and recent graduates were surveyed. Individuals were identified through the Society of General Internal Medicine associates' mailing list and solicitation of program directors. Nonfellow associates served as the proxy group for potential fellows. MEASUREMENTS AND MAIN RESULTS: 579 surveys were mailed; 348 (60%) responses were received, of which 288 (50%) were suitable for analysis. Of all respondents, 38% were current fellows and 40% were recent graduates. When asked to prioritize educational needs during fellowship training, respondents ranked research methodology, ambulatory medicine, critical review of the literature, epidemiology, biostatistics, teaching skills, medical consultation, grant writing, preventive medicine, and design of educational curriculum as the top ten. Only minor deviations in rank order were found between graduates and nongraduates. Mean Likert scale scores for degree of emphasis of each curricular element in graduates' actual fellowships were compared with mean scores for graduates' ideal fellowship descriptions. High-priority elements that were perceived as adequately emphasized included research methodology, critical analysis of the literature, epidemiology, and biostatistics. High-priority elements that were perceived as inadequately emphasized included ambulatory medicine, teaching skills, medical consultation, grant writing, preventive medicine, and design of educational curricula. CONCLUSIONS: FGIM largely meet the expectations of their fellows for preparation for research responsibilities. However, several curricular elements concerned with preparation for future clinical and teaching responsibilities are perceived by graduates as underemphasized. These areas deserve increased emphasis during fellowship training to better prepare fellows for their future roles in academic general internal medicine. PMID- 1744765 TI - Physician-patient gender congruence and the physical examination. AB - To assess the hypothesis that breast, genitourinary (GU), and rectal examinations are performed more frequently when the physician and patient are of the same gender, the authors reviewed the records of 529 patients in a housestaff medical clinic. They found no significant difference between gender-congruent and gender incongruent patient encounters in the rates of these examinations. However, higher rates of performance by primary care housestaff compared with those of internal medicine housestaff were noted in all categories. The authors conclude that performances of breast, GU, and rectal examinations were not related to gender congruence but may have been associated with the houseofficers' training program. PMID- 1744766 TI - The procedural and interpretive skills that third-year medicine clerks should master: views of medicine clerkship directors. AB - The authors surveyed medicine clerkship directors to determine which procedural and interpretive skills they felt third-year medical students should acquire. Of the 101 (81%) who responded, 91 felt that specific procedural and interpretive skills should be achieved by the end of the third-year medicine clerkship. Twenty seven percent of these 91 reported having students keep a record of their activities; 35% reported testing students in the interpretation of various tests used in the evaluation of hospitalized patients on medicine services; and one clerkship director reported that his students were tested in their abilities to perform procedures. There was substantial disagreement by medicine clerkship directors over the procedural and test/study-interpretation skills in which medicine clerks should become proficient during the third-year medicine clerkship. PMID- 1744767 TI - Vitamins and minerals in HIV infection. PMID- 1744768 TI - Status panic among physicians. PMID- 1744769 TI - Predicting readmissions of elderly patients. PMID- 1744770 TI - Evaluating the quality of qualitative research: a proposal pro tem. PMID- 1744771 TI - Nurses evaluating humanism. PMID- 1744772 TI - Tetanus immunization of the elderly. PMID- 1744773 TI - Image invariance with changes in size: the role of peripheral contrast thresholds. AB - The appearance of objects generally does not change with changes in the size of their retinal image that occur as the distance from the observer increases or decreases. Contrast constancy ensures this invariance for suprathreshold image features, but fully robust size invariance also requires invariance at threshold, so that near-threshold image features do not appear or disappear with distance changes. Since the angular size and the eccentricity of image features covary with distance changes, the threshold requirement for invariance could be satisfied approximately if contrast thresholds were to vary as the product of the spatial frequency and the eccentricity from the fovea. This model fits contrast thresholds for orientation identification over spatial frequencies of 1-16 cycles/deg and for retinal eccentricities of as much as 23 deg. Contrast detection thresholds from six different studies conform to this model over an even wider range of spatial frequencies and retinal eccentricities. The fitting variable, the fundamental eccentricity constant, was similar for all three studies that measured detection along the horizontal meridian and was higher for the orientation identification contrast thresholds along the same meridian. The eccentricity constant from studies that measured detection along the vertical meridian was higher than the constant calculated for the horizontal meridian and lower than the eccentricity constant for chromatic isoluminance gratings. Our model and these results provide new tools for analyzing the visibility of displays and for designing equal-visibility or variable-visibility displays. PMID- 1744774 TI - Peripheral spatial vision: limits imposed by optics, photoreceptors, and receptor pooling. AB - We examined the contribution of optical and photoreceptor properties as well as receptor pooling to eccentricity-dependent variations in spatial vision by comparing the performance of ideal observers with that of human observers. We measured contrast sensitivity functions in human observers and calculated such functions in ideal observers for retinal eccentricities of 0-40 deg. Comparisons of human and ideal performance in a variety of tasks reveal that many aspects of the variation in spatial vision with eccentricity can be understood from an analysis of the discrimination information available at the retinal ganglion cells. PMID- 1744775 TI - Birefringence of the human crystalline lens in vivo. AB - We studied aspects of the birefringence in the human crystalline lens. With the use of Mueller-matrix ellipsometry in vivo on both accommodated and unaccommodated eyes, we found no difference between the associated retardations. We calculated form birefringence of the lens by interpreting the membranes of the lens fiber cells as Wiener bodies. The resulting retardation for a light beam that passes the lens as in the experiments exceeds by far the measured total retardation. We conclude that form and intrinsic birefringence of the lens cancel out. PMID- 1744776 TI - Stimulus determinants of achromatic constancy. AB - Achromatic constancy refers to the invariance of either lightness or brightness despite changes in illumination intensity. Previous results disagree as to the extent to which constancy occurs with fixed luminance ratio conditions. This may reflect a lack of distinction between lightness and brightness. We measured both lightness and brightness constancy with fixed luminance ratios between test and annular fields under conditions varying in stimulus duration and adaptation. Lightness constancy occurred for all ratios under sustained viewing conditions and irrespective of adaptation level. Brightness constancy occurred for high contrast stimuli and under sustained viewing conditions. These results support a bidimensional description of achromatic stimuli and suggest that lightness and brightness are the outcomes of two functionally distinct processes. PMID- 1744777 TI - Influence of shape and perimeter length on induced color contrast. AB - The magnitude of induced color contrast was measured for tests whose areas, perimeter lengths, and shapes were independently varied. Test shapes were smoothly contoured, multiple-lobed figures generated from unitary Fourier shape descriptors. The shapes had from 3 to 40 lobes and were equal in area to a disk of diameter 2 deg, with perimeter lengths of 1.25, 1.75, 2.25, and 2.75 times the circumference of a 2-deg disk. The surround was a 5-deg disk. The surround was modulated sinusoidally along one of the three cardinal directions of color space around an equal-energy white of 50 cd/m2. The observer nulled the modulation induced into the test by adjusting the amplitude of real modulation in the test. The amplitude of nulling modulation was the measure of induction. The main result was that the amount of induction was similar for all tests of equal area irrespective of the shape or the length of perimeter. PMID- 1744778 TI - Effects of chromatic adaptation on opponent interactions in monkey increment threshold spectral-sensitivity functions. AB - The effects of chromatic adaptation on the opponent interactions of cone mechanisms were investigated by using increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus-radiance (TVR) curves in rhesus monkey subjects. The TVR curves showed shape- and field-sensitivity invariance for both 580- and 500-nm adapting backgrounds and indicated that three cone mechanisms were mediating detection over moderate adapting-field intensity levels. Differential adaptation between the long-wavelength-sensitive (L) and the middle wavelength-sensitive (M) opponent (L - M) and nonopponent (L + M) channels and the short-wavelength-sensitive (S) channel caused changes in the shape of the ITSS function as the adapting-field intensity was increased without changes in the level of cone interaction. Chromatic adaptation also resulted in significant changes in the shape of the ITSS functions, but it still exhibited characteristic L-M opponent interactions. Converting ITSS data to cone-contrast coordinates for R-G adapting fields indicated that the relative contribution of the L and M cones at the second site was approximately equal (detection contour slope approximately 1). Consequently, most of the changes in the shape of ITSS functions under chromatic adaptation are explained by the von Kries adaptation principle. ITSS functions on a green background also exhibited opponent interactions between S cones and longer-wavelength cones. The cone-contrast coordinates, when expressed for S cones, showed that the inhibitory interactions occur because the S-cone signal subtracts from both M and L cones. PMID- 1744779 TI - On the germ theory of disease. PMID- 1744780 TI - A comparison of bacterial resistance to antimicrobials in Riyadh, Medina, and Oklahoma City. AB - Many bacteria are known to develop resistance to anti-microbial agents following their clinical use. The resistance pattern varies from one geographic location to another depending upon the patient population and local history of antibiotic use. The bacterial resistance to commonly used antimicrobial agents in Oklahoma City was found to be different from two cities in Saudi Arabia, especially amongst Gram-negative bacilli. A total of 13,575 fresh clinical isolates from the Veterans Administration Medical Center (VAMC), Oklahoma City, Oklahoma; the King Faisal Specialist Hospital and Research Centre (KFSH), Riyadh; and the King Fahad Hospital (KFH), Medina, Saudi Arabia; were used. There were 6,270 isolates of Enterobacteriaceae, 2,799 pseudomonads and Acinetobacter, and 4,506 Gram positive strains of staphylococcus bacteria. Gram-negative bacteria from KFH were considerably more resistant to ampicillin, gentamicin, and trimethoprim sulfamethoxazole than at KFSH and VAMC. On the other hand, Staphylococcus aureus isolated from VAMC exhibited a significantly higher degree of resistance to oxacillin and trimethoprim-sulfamethoxazole than those at KFSH and KFH. PMID- 1744781 TI - The descriptive epidemiology of Lyme disease in Oklahoma. AB - Lyme disease is a tick-borne illness that primarily occurs in the United States in three endemic areas: the northeast, upper midwest, and pacific coastal regions. Although Oklahoma is considered a non-endemic area of Lyme disease, other tick-borne infections such as Rocky Mountain spotted fever, ehrlichiosis, and tularemia occur at endemic levels. In order to determine the extent of Lyme disease in Oklahoma, the Oklahoma State Department of Health collected information on all possible cases of Lyme disease. The first reported Oklahoma case occurred in 1985. In 1988, and 1989, 8 and 25 cases, respectively, of Lyme disease were reported in Oklahoma residents who acquired their infection indigenously. The mean age of case-patients was 38 years. Twenty-eight of 33 (85%) case-patients were white, and 4 of 33 (12%) were American Indian (race was unknown for 1 case-patient). The female/male ratio was 2.3. Most case-patients had onset of illness between May and September. Twenty-two counties reported cases, with Oklahoma County accounting for 4 of 33 (12%). Only 21 of 33 (64%) recalled a tick bite, and only 19 of 33 (58%) had erythema migrans. Continued active case-finding and passive reporting (as now mandated by state law) will further increase our knowledge of the epidemiology, ecology, and prevention of Lyme disease in Oklahoma. PMID- 1744782 TI - A comparison of human and animal mouth flora. AB - Human bite injuries are often believed to be more serious than animal bite injuries. One reason for this distinction might be a species difference in the microbial mouth flora. In order to compare this possibility, we cultured the mouths of humans, dogs, and cats. Human oral flora contained the smallest number of bacteria followed by dog and cat oral flora, respectively. Veillonella parvula was cultured from all humans and was also found in dog and cat mouths, but less frequently. V parvula is not usually considered a virulent organism but occasionally may become a pathogen and should not be overlooked especially following human bite injury. PMID- 1744783 TI - Patient demographic characteristics and housestaff performance in the care of patients with human immunodeficiency virus disease. AB - A retrospective review of the medical records of 45 patients with human immunodeficiency virus (HIV) disease was conducted in an Oklahoma internal medicine teaching clinic. Demographics of this patient population and house staff performance in the care of these patients was evaluated. The study population demographics were similar to national findings with the exception of lower documented homosexual/bisexual transmission among males and higher heterosexual transmission among females. Deficiencies in documentation were noted in the areas of route of acquisition, mental status, and functional level. In several instances patients who were candidates for zidovudine and/or Pneumocystis prophylaxis were not receiving these treatments. The quality of care could be enhanced through the use of HIV evaluation and treatment protocols as well as specially designed, HIV-specific medical records to improve data collection. These HIV-specific medical records can be found in the appendices. PMID- 1744784 TI - [Effects of heavy metal ions in endocochlear DC potential and cochlear microphonics in the guinea pig--the influence of calcium on the cochlea]. AB - Endocochlear DC potential (EP) and cochlear microphonics (CM) in the guinea pig under the influence of the divalent heavy metal cations of manganese, nickel, cobalt and cadmium, and the trivalent cation of lanthanum were investigated. The area from the scala tympani to the scala vestibuli was perfused with control and test solutions. CM decreased gradually to 50-80%, but EP showed no change after perfusion with a solution containing 1 mM of metal ions. At a concentration of 10 mM, EP decreased from 80 mV to 10-20 mV and CM decreased to 15-55%. At 100 mM, EP increased by about 10 mV at the beginning of perfusion, remained steady for 1 min, and then rapidly decreased to 0-10 mV. Meanwhile, CM continued to decrease, finally sustaining a 10-56% reduction. The decrease in EP and CM were irreversible, and perfusion of the area with the standard solution for 20 min had no effect. The osmolarity of the artificial perilymph containing 100 mM of metal ions was twice as high as that of the normal physiological solution. The effects of osmolarity, however, were excluded because perfusion with an artificial perilymphatic solution made hypertonic by either NaCl or sucrose changed neither EP nor CM. The application of 100 mM of metal ions topically to the round window membrane caused no change in EP. The alkali metal ions are known to inhibit inward Ca2+ current. Therefore, the present results suggest that Ca2+ ions play a role in maintaining EP generation in the stria vascularis and CM generation in the organ of Corti. PMID- 1744785 TI - [Subclinical swallowing disorder in patients with abnormal sensation in the throat]. AB - Measurement of swallowing pressure was done in 75 patients who complained of abnormal sensation such as obstructive sensation, difficulty in swallowing, etc. in the throat without noticeable cause. Abnormal swallowing pressure curves were observed in 33 patients (44%), and 76% of them showed abnormal elevation of the pressure at the hypopharyngeal or cervical esophageal region. These results indicated that subclinical swallowing disorder, particularly abnormal high swallowing pressure, can be a possible cause of their complaints. The author assumed that abnormal elevation of swallowing pressure is due to hypertonicity of the hypopharyngeal and cervical esophageal muscles. By the animal experiments using dog, a muscle relaxant, eperizone hydrochloride, revealed to change muscle tonus of the hypopharyngoesophageal muscles. Intravenous administration of the drug decreased swallowing pressure and prolonged the relaxation time of the cricopharyngeal muscle. Clinically the muscle relaxant showed to be effective in ameliorating the complaint of the patients with abnormal high swallowing pressure at the hypopharyngeal or cervical esophageal region. Based on the above results, the author proposed that the clinical entity, hypopharyngeal-cervical esophageal hypertonicity, causes a subclinical swallowing disorder leading to the abnormal sensation in the throat. PMID- 1744786 TI - [Antibody-producing ability of mononuclear cells from human tonsils: a consideration for immunological pathogenesis and operative indication of recurrent tonsillitis]. AB - Antibody-production of mononuclear cells from human tonsils was examined by enzyme-linked immunosorbent assays in the culture system following polyclonal stimulations with pokeweed mitogen. The results were summarized and discussed as follows; 1) Age-related changes were not observed. 2) Antibody-producing ability in the intermittent phase of recurrent tonsillitis was significantly impaired. 3) Antibody-production in the recrudescent phase of recurrent tonsillitis was increased and might be reactivated probably by stimuli of the recent infection in vivo. 4) It was suggested that the recurrent tonsillitis was due to the low antibody-production ability of tonsillar mononuclear cells. 5) These results gave an immunological basis on the operative indication of recurrent tonsillitis. PMID- 1744787 TI - [Conventional X-ray versus CT in diagnosis of chronic sinusitis in children]. AB - The interpretation of conventional radiographic views for sinusitis in children has given rise to considerable controversy. Thirty-three children (66 sides of sinuses) aged from 4 to 15 years who were suspected of having chronic sinusitis were studied to determine the accuracy of conventional X-ray examination, comparing the results with those of CT. Coronal CT was taken after conventional X ray examination (Waters and occipito-frontal views), and the time interval between these two examinations was 0 to 14 days (average 5.1 days). The rate of correspondence in diagnosis of sinus pathology between conventional X-ray views and CT was 74.3% in the maxillary sinus and 40.9% in the ethmoid. The rate of overestimation with conventional X-ray views was 24.2% in the maxillary sinus and 56.1% in the ethmoid, while that of underestimation was 1.5% and 3.0% in the maxillary and the ethmoid sinus respectively. The incidence of false positives according to conventional X-ray views was 8.0% in the maxillary sinus and 33.3% in the ethmoid. Our results indicate that Waters view is sufficient to diagnose maxillary sinus pathology in children. However, additional radiologic examinations, such as CT, are necessary in investigating the pathologic conditions of the ethmoid sinus, since diagnostic significance of occipito frontal view for ethmoid pathology is doubtful in children. A routine preoperative CT is recommended, which allows a detailed evaluation of pathologic changes and anatomical relations of the ethmoid before embarking a surgical intervention for the ethmoid sinus in children. PMID- 1744788 TI - [A case of bilateral nontraumatic internal carotid aneurysms presenting with recurrent massive epistaxis]. AB - A case of bilateral nontraumatic internal carotid aneurysms presenting with recurrent massive epistaxis was reported. A 37-year-old female complaining of massive epistaxis from the left nostril was admitted to our hospital. After admission, she experienced recurrent massive epistaxis, but had no cranial nerve palsies. Carotid angiography demonstrated an aneurysm of the cavernous portion of the left internal carotid artery partially protruding into the sphenoid sinus. Neck clipping of the aneurysm was unsuccessful, therefore the left internal carotid ligation in the neck was performed with a Selverstone clamp. After the ligation, no rebleeding and neurological deficits occurred. Postoperative carotid angiography showed an aneurysm of the right internal carotid artery at the same site. The carotid angiography of 3 months later and 1 year and 3 months later revealed that the left aneurysm decreased in size and the right one remained unchanged. Twenty-one cases including ours that presented nontraumatic internal carotid aneurysm of the cavernous portion were reviewed. Twelve cases had no cranial nerve palsies, and 7 cases including ours had no other symptoms than massive epistaxis. Because massiveness of epistaxis from an internal carotid aneurysm often threatens one's life, diagnosis should be made by carotid angiography as soon as possible. There are several surgical procedures for such aneurysms. Clipping is the ideal method which can interrupt the blood flow to the aneurysm completely, but it is very difficult to be performed anatomically. Carotid ligation in the neck with little surgical invasion was an excellent method in 7 cases without rebleeding and neurological deficits. Bilateral intracavernous internal carotid aneurysms were found in our case and another case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744789 TI - [Nonsequential vector analysis of body sway in Meniere's disease]. AB - Body sway test which examines the vestibulo-spinal reflex is sensitive for evaluating vestibular dysfunction in patients with vertigo, dizziness or unsteadiness. Body sway is usually evaluated by measuring the length and area of traces on the force platform. However, it is not necessarily possible to evaluate abnormal body sway with these indicators because there is a discrepancy between sway length and area. In the present study, 8 directional vectro-posturography was developed and applied to the patients with Meniere's disease. Averaging of measurements at moving 3 points was used to eliminate high frequency noise over 4.92Hz. The subjects consisted of 66 patients with unilateral Meniere's disease and 31 normal controls. Eight directional vectrogram allowed measurement of shift area and directionality, simultaneously. The patient's group showed statistically significant body sway in the right forward and left backward direction with eyes open, in all the directions with eyes closed, when compared with the control's group. The effect of vision on postural stability was studied by obtaining 8 directional Romberg's quotients. The patients with Meniere's disease had significantly in forward-backward, and left-forward and right-backward direction when compared with controls. However, laterality of the affected side was not detected from the vectrogram. The effect of endolymphatic sac operation on postural stability was evaluated in the patients of unilateral Meniere's disease who showed progressive hearing loss and resisted conservative medication therapy. The results showed unstable body sway in the condition with eyes closed until at least 4 months after the operation. The patients with Meniere's disease presented pathological body sway, even during symptom free periods, when examined with 8 directional vector posturography. Power spectral analysis of body sway indicated that most energy was distributed at frequencies lower than 0.5Hz. Nevertheless, directional preponderance of body sway was characterized by higher frequency components. The findings infers that postural stability at the frequency range over 0.5Hz, may be governed by the input of vestibular organs. PMID- 1744790 TI - [Allergic rhinitis nasal epithelial cell conditioned medium stimulates growth and differentiation of basophil/mast cell and eosinophil progenitors from atopic blood]. AB - We examined the conditions, kinetics and cell sources for basophil/mast cell and eosinophil colony stimulating activity (CSA) production by nasal epithelial cells taken from house dust (HD) nasal allergic patients. Epithelial scrapings removed from HD nasal allergic patients were grown to confluence over 7 days as a monolayer of epithelial cells in medium supplemented with fetal calf serum (FCS) on collagen coated microwell plates. CSA in nasal epithelial cells conditioned medium (CM) was assessed with density-gradient separated, nonadherent peripheral blood mononuclear cells in 14-day and 21-day methylcellulose assays. In the 14 day methylcellulose assays, the number of Eo-type colonies in the presence of either 10% or 5% CM was significantly higher than the background number of Eo type colonies (negative control). Comparison of Gm CSA among 1%, 5% and 10% CM with negative, revealed no significant differences. We also compared the Eo-type CSA in the presence of 10% significant differences. We also compared the Eo-type CSA in the presence of 10% CM in the 14-day methylcellulose assay with 21-day methylcellulose assay. There was no significant difference in the number of Eo type colony between the 14-day and 21-day methylcellulose assays. We also examined the composition of the cells in the colonies in the 14-day and 21-day methylcellulose cultures. The percentage of metachromatic granule containing cells in a Eo-type colony in 14-day methylcellulose assay was significantly higher than in a Eo-type colony in 21-day methylcellulose assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744791 TI - [Problems in evaluating the efficacy of treatment of sudden deafness]. AB - 1) The indices of hearing recovery for sudden deafness was examined. Because it did not reflect the severity of the initial hearing loss, the standard of the Japanese Ministry of Welfare was thought to be inadequate. 2) Since the prognosis of sudden deafness was known to be influenced by several factors, it seemed to be necessary for evaluating the efficacy of treatment to exclude various modifying factors. For this purpose predicting hearing recovery based on multiple regression analysis is appropriate. 3) The predicting recovery rate with the actual recovery rate for 4 kinds of treatment was compared. No significant difference was found between the expected values and the observed values. 4) The scatter diagram indicated 2 groups of patients. This might be due to different pathophysiology of sudden deafness. In the good recovery group, the recovery rate for prostaglandin E1 therapy was significantly better than the expected one. PMID- 1744792 TI - [Effect of recognition of head and neck malignancies on patients' psychosomatic condition and personality]. AB - In order to elucidate the effect of recognition of head and neck malignancies on patients' psychosomatic condition and personality, we applied the Cornell Medical Index Health Questionnaire (CMI) and the Maudsley Personality Inventory (MPI) and collected medical and psychological data from 35 male (42-78 years of age; average 62.5) and 15 female (20-76 years of age; average 54.7) patients with malignant head and neck tumors (10 nose and paranasal, 8 oral, 8 pharyngeal, 14 laryngeal, 6 thyroid gland and 4 others). The two tests were done twice for each patients; at first immediately before hospitalization for treatment of the tumors at Mie University Hospital and secondly just before discharge from the hospital. The period of hospitalization ranged 1 to 13 months, average 3.3 months. At the end of hospitalization doctors and nurses who had mainly taken care of the patients estimated the patients' recognition of their malignancy by analyzing behavior and information mainly from their family and classified patients into three groups; Group R (Patients who recognized that they were patients with head and neck malignancies) comprised 22 patients, Group N (who did not recognize the condition) comprised 15 and Group U (who could not be classified into Groups R or N) comprised 13. Comparison among the three groups revealed the followings. 1) Patients in Group R were relatively young (average 56.3 years) and extrovert (estimated by MPI) and their somatic and psychological complaints registered on the CMI were less than those in other 2 groups. Psychosomatic condition after recognition that they had been patients with malignant tumors was better than before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744793 TI - [A study on the tonsil with focal infections--with special reference to the newly devised tonsillar cryptscope and the architecture of vessels in crypts]. AB - It is well known that inflamed human palatine tonsils have many surface crypts showing characteristic lymphoepithelial symbiosis, which play an important role in immune response. The cryptepithelia are rich in blood vessels. This proliferation of blood vessels is said to be the initiation of various kinds of immune responses. We devised a tonsillar cryptscope in order to observe the tonsillar crypt. Scopy with the cryptscope confirmed seven characteristic types of capillary vessels. The cryptscopic figures showed different patterns in tonsillar diseases such as hypertrophic tonsil, recurrent tonsillitis and tonsil with focal infection (palmoplantar pustulosis and psoriasis vulgaris). In this study the significances of tonsillar cryptscopic figures were investigated through the study of three dimensional structures of blood vessels and immuno histology. In order to understand the structure of capillary vessels in details, human palatine tonsils were studied using corrosion casting techniques with a scanning electron microscope. Horseshoe type capillary vessels corresponded to the curved capillary vessels in the epithelium. This type of capillary vessel was observed in the epithelia covering the interfollicular area. The tonsillar blood vessels, along with closely related substances in the epithelium and the parenchyma, were immuno-histologically examined. Where the lymphocytes had densely infiltrated the epithelium, the basement membrane became thickened and often disrupted; the endothelial cells were also enlarged. Adrian et al reported that lymphocytes invaded from the capillary vessels within the epithelia. Thus it was suggested that the horseshoe type was related to lymphocyte invasion of the epithelia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1744794 TI - [Transcranial color Doppler guided Matas' test]. AB - Carotid artery involvement in head and neck tumor is a great concern to surgeons because of the unpredictable effects of its resection. For the investigation of brain collateral circulation, color Doppler guided Matas' test has been performed to examine blood flow in the middle cerebral artery (MCA) and internal carotid artery (ICA). SSA-270A convex (3.75MHz) and linear (3.75MHz, 2.5MHz) array probes (Toshiba Co., Ltd.) were used for this investigation. A temporary occlusion test (60 sec) was performed on the common carotid artery (CCA) in thirty patients who were scheduled to undergo radical neck dissection. The blood flow velocity of MCA during Matas' test was recorded. Then relative flow (percent blood flow before the test) of MCA during the 60 sec Matas' test was measured. The relative mean flow was 72% with a standard deviation of 15%. The results of thirty patients were classified into four groups according to the relative flow of MCA after 60 sec occlusion of the common carotid artery: Group A, over 87% (three cases); Group B, 86-72% (twelve cases); Group C, 71-57% (twelve cases); Group D, under 56% (three cases). Brain collateral circulation (BCC) of the Group A patients was considered to be excellent, and therefore reconstructive vascular surgery (RVS) was not necessarily indicated. In Group B patients (fair) and Group C patients (slightly poor) further investigation of BCC, i.e., Balloon Matas' test (occlusion of CCA and ICA), SPECT and brain angiography, was considered to be necessary. In Group D patients (poor) RVS was inevitable if either CCA or ICA had to be resected. Important information is provided by this noninvasive examination to predict the risk of carotid resection. This test seems to be useful to determine whether or not RVS is indicated. PMID- 1744795 TI - [Application of color Doppler to the head and neck region]. AB - In the diagnosis of the head and neck region it is important to investigate the relationship between the lesions and surrounding vessels, including their hemodynamics, pre- and/or postoperatively. For this purpose color Doppler has been used in recent years. However, there is little information on the use of color Doppler in this region. This report describes an attempt to apply this examination to the region of the head and neck. Standard methods of detection of the main arteries and internal jugular vein have been devised, and the blood velocity and flow of those arteries were measured using SSA-270A convex (3.75 MHz) and linear (3.75 MHz, 2.5 MHz) array probes (Toshiba Co., Ltd.). This technique was also applied to several clinical cases. The results of these investigation were as follows. 1) The middle cerebral, vertebral and basilar, and carotid arteries and their branches could be studied. 2) Blood velocity and flow of the main arteries were reasonable when compared with the results of scintigraphy and electromagnetic studies. 3) The vessels surrounding the tumors were easy to detect. The location or hemodynamics of metastatic tumors, pseudoaneurysm, and tongue hemangioma could also be displayed. The technique was also useful for the blood flow estimation in the portion of vascular anastomosis. PMID- 1744796 TI - The expression of parathyroid hormone messenger RNA in normal and abnormal parathyroid tissue. AB - The distribution and expression of preproparathyroid hormone (PTH) mRNA were investigated in parathyroid tissue from 57 parathyroidectomy specimens. PTH mRNA was detected by in situ hybridization using digoxigenin-labelled oligonucleotide probes. Cell morphology was seen to correlate with PTH mRNA expression. Strong expression of PTH mRNA was confined to cells which on haematoxylin and eosin staining had large vesicular nuclei. These included both vacuolated and non vacuolated cells. Chief cells with small dark nuclei and scanty cytoplasm had little or no expression. In both adenoma and chief cell hyperplasia, the striking difference from normal was the greatly increased proportion of cells expressing PTH mRNA. In adenomas, the rim of uninvolved parathyroid tissue showed PTH mRNA expression similar to that of normal parathyroid. In hyperplasia, there was frequently concordance of staining within individual nodules. The findings establish morphological criteria for activity of parathyroid tissue and support current concepts of the different pathogenesis of hyperplasia and adenoma. The expression of PTH mRNA in oxyphil change and parathyroid carcinoma was also investigated. PMID- 1744797 TI - Leakiness of gastric superficial and foveolar cells. A quantitative electron microscopic study using tannic acid. AB - Two adjacent antral biopsies were taken endoscopically from 41 patients attending a clinic for the investigation of upper gastrointestinal tract symptoms. One was processed for histopathological grading and assessment of the Helicobacter pylori by light microscopy. The other was fixed in tannic acid, which demonstrates cell leakiness, and processed for electron microscopy. On each grid, the light (electron lucent) and dark (electron dense-leaky) gastric superficial and foveolar cells away from mechanical trauma of biopsy were counted, along with the number of H. pylori which were in contact with the epithelial cells. There was a significant relationship between histological grade of gastritis and the extent of electron microscopic damage, i.e., the degradation of normal to leaky cells and the number of H. pylori per leaky cell. If the patients were divided into two groups with minimal and maximal gastritis and compared against each other, then there was a significant difference between the two groups with respect to surface cell damage, polymorphs per unit area, the number of glands invaded by polymorphs, light/dark cells, Helicobacter grades assessed light microscopically or totals counted in contact with epithelial cells by electron microscopy, the number of Helicobacter per cell, and the age of the patients. There was no difference between the two groups on their endoscopic appearances or treatment with H2 blockers or NSAIDS. PMID- 1744798 TI - CD23 expression in non-Hodgkin lymphoma: immunohistochemical demonstration using the antibody BU38 on paraffin sections. AB - The leucocyte antigen CD23 is upregulated in the early stages of B-cell activation by Interleukin-4 (IL-4), and functions as an IgE receptor and lymphocyte growth factor. We have studied the expression of CD23 in 68 cases of non-Hodgkin lymphoma (NHL) using the antibody BU38. This new antibody has the great advantage of being applicable to routinely-processed paraffin sections. CD23 was expressed in tumour cells in 27 out of 36 cases of low grade NHL and 3 out of 32 cases of high grade NHL. Follicular dendritic cells were strongly positive and were seen in follicular lymphomas. Macrophages were also positive and were numerous in high grade lesions. PMID- 1744799 TI - MHC antigen expression in human oral squamous carcinoma cell lines. AB - This study quantified the constitutive and interferon-gamma (IFN-gamma) stimulated expression of MHC class I (HLA-ABC and beta 2 microglobulin) and class II antigens (HLA-DR, -DP, -DQ) on normal and malignant oral keratinocytes using radioimmunoassay and immunocytochemical techniques. Normal keratinocytes and three of four malignant cell lines (H103, H157, H314) expressed MHC class I antigens constitutively; IFN-gamma increased MHC class I expression with significant changes in normals, H157 and H314. Normal keratinocytes expressed significantly more constitutive MHC class I antigens than H103 and H157 and significantly more IFN-gamma stimulated MHC class I antigens than H103, H157 and H314. MHC class II antigens predominantly were not expressed constitutively on normals, H103 and H157 but, in H314, HLA-DR, -DP and -DQ antigens were demonstrated on 35, 11 and 5 per cent of cells, respectively, and resulted in a non-coordinated pattern of expression (HLA-DR greater than -DP = -DQ). IFN-gamma induced HLA-DR on normals, H103 and H157, whilst HLA-DP and -DQ remained undetectable. In H314, IFN-gamma enhanced HLA-DR, -DP and -DQ (significant increase of HLA-DQ) but the interrelationship between these antigens was maintained (HLA-DR greater than -DP = -DQ). Normal keratinocytes expressed significantly more IFN-gamma stimulated HLA-DR than H103 and H157 but significantly less HLA-DR than H314 under similar experimental conditions. One oral malignant cell line (H191) did not express MHC class I and MHC class II antigens either constitutively or in response to IFN-gamma. The results demonstrate aberrant patterns of MHC expression (absence, enhanced, diminished) in the different malignant oral keratinocyte cell lines. PMID- 1744800 TI - Immunocytochemistry of malignant mesothelioma: OV632 as a marker of malignant mesothelioma. AB - In pleural or ascitic effusions the cytomorphological distinction of adenocarcinoma cells, reactive mesothelial cells, and malignant mesothelioma cells often causes a diagnostic dilemma. The value of immunocytochemistry was investigated on cytological smears of 24 well-established cases of malignant mesothelioma, a selected series of 31 metastatic adenocarcinomas, and 20 smears of patients without known malignancy. In these smears we scored the immunoreactivity with a panel of four monoclonal antibodies. In addition to antibodies for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), the monoclonal antibody MOC31 and the ovarian carcinoma specific antibody OV632 were incorporated in the panel. With none of these four antibodies was immunostaining of reactive mesothelial cells found. CEA- and MOC31-positive tumour cells were frequent in metastatic adenocarcinomas, but occurred rarely in malignant mesotheliomas. EMA-positive tumour cells were found in all metastatic adenocarcinomas (100 per cent) and in most malignant mesotheliomas (83 per cent). In addition to the expected reactivity of OV632 with ovarian carcinomas, 22 of 24 malignant mesotheliomas contained immunopositive tumour cells, while only a small proportion of non-ovarian adenocarcinomas reacted with this antibody. This selective staining of malignant mesothelioma cells, but not reactive mesothelial cells, with OV632 now permits the positive identification of malignant mesothelioma cells in male patients. PMID- 1744801 TI - Composition and organization of cell-substratum contacts in normal and neoplastic renal epithelium. AB - We have investigated the molecular basis of the organization of cell-substratum contact in normal and neoplastic renal epithelium. The several components of focal contacts and non-collagenous basement membrane glycoproteins have been identified by antibodies, detected by immunofluorescence and viewed by laser scanning microscopy. Tubular epithelial cells grown on glass coverslips expressed laminin at the cell periphery. Co-localized with laminin were receptors of the beta 1 integrin class, and the cytoplasmic plaque proteins vinculin and talin. When basement membrane glycoproteins laminin or fibronectin were exogenously supplied by growing cells on coated coverslips, the vinculin-, talin- and integrin-containing contacts became organized into linear arrays with intervening free cell membranes. Under these conditions the actin cytoskeleton became highly organized. By contrast some tumour cells showed a reduction in focal contact molecules and a failure to organize these structures in response to laminin or fibronectin. This loss of cell matrix interaction may be important during the progression of renal tumours. PMID- 1744802 TI - LPD, a glandular or vascular problem? PMID- 1744803 TI - Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells. AB - This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes. PMID- 1744804 TI - Behavior problems and adaptive functioning in children with mild and severe closed head injury. AB - Assessed behavior problems and adaptive functioning in children with mild or severe closed head injuries, on average more than 2 years postaccident. To ensure that any problems detected in the present study were not merely preexisting problems, potential subjects were excluded if there was a history of preexisting CNS damage, significant developmental delay, or behavior problems. Children with severe head injuries had an excessive rate of behavior problems and impaired adaptive functioning. Children with mild head injuries also had an excessive rate of behavior problems (comparable to that of children with severe head injuries) but did not have impaired adaptive functioning. Results are discussed in terms of six alternative ways brain injury and behavior problems can be related functionally. PMID- 1744805 TI - Disease experience and psychosocial adjustment in children with juvenile rheumatoid arthritis: children's versus mothers' reports. AB - Adjustment in children with juvenile rheumatoid arthritis (JRA) has been evaluated most frequently by parental or teacher reports and with reference to disease severity. In this study, 38 children, ages 7 to 13 with JRA, and their mothers were interviewed. Modest correlations were found between children and mothers in their assessments of children's perceived competence in several domains (i.e., athletic competence, social acceptance, physical attractiveness, and global self-worth) and in their perceptions of how JRA is experienced by children and families. Children's perceptions of the disease experience were significantly correlated with the four measures of perceived competence, even after controlling for disease severity. The results highlight the importance of cross-validating parental reports with children's self-reports, and demonstrate the need to consider variables other than disease severity--in particular how JRA is interpreted by children--in predicting their adjustment. PMID- 1744806 TI - Neuropsychological function in young children who have undergone liver transplantation. AB - Presented neuropsychological data from 20 patients between the ages of 4 and 9 years, who had undergone liver transplantation at least 12 months prior to study participation, and compared them to a control group of 20 children with cystic fibrosis. The liver transplant group showed deficits in VIQ, PIQ, visual-spatial and abstraction/reasoning skills, but not in alertness/concentration, motor, or sensory-perceptual functions. On motor and sensory-perceptual tests, no differences were found in direction of lateralization of deficits. Visual-spatial deficits found in this study sample are similar to those found in adults with end stage liver disease and in a previous report of an overall older group of children following liver transplantation. However younger children have greater evidence of generalized impairment and VIQ deficits which have not been found in older groups. Findings are discussed in relation to possible etiology, location of brain damage, and clinical implications. PMID- 1744807 TI - A comparison of memory and attention in Turner syndrome and learning disability. AB - Compared short-term verbal memory, sustained attention, and impulsivity in 13 children with Turner syndrome to 13 females and 14 males with learning disability who had neuropsychological patterns similar to the children with Turner syndrome. Similar patterns of short-term memory deficits were found in all three groups. There were no significant differences among the groups on computer measures of sustained attention and impulsivity. However, extreme variability of the attention and impulsivity scores for the Turner syndrome group may reflect atypical attention deficit disorder in some of these children. PMID- 1744808 TI - Prevention of spinal cord injury: an elementary education approach. AB - Spinal cord injury (SCI) results in permanent paralysis and most often happens to teenagers and young adults. High risk behaviors are most often the cause; therefore these injuries are often preventable. In response to a gap in existing prevention programs, an elementary age SCI prevention program was developed, designed for implementation by teachers. Evaluation was carried out via a quasi experimental pre-post comparison group design. Experimental students demonstrated significantly improved knowledge of SCI and its prevention. Similar changes in self-reported safety belt use were not noted. Development of the curriculum, related grant activities, and plans for national dissemination are described. PMID- 1744809 TI - Cognitive remediation in pediatric head injury: a case study. AB - Little work has been done in delineating cognitive remediation approaches for pediatric survivors of head injury. The use of a cognitive remediation approach is described in a case study of a 16-year-old male, who was 1 1/2 years post severe traumatic brain injury. Specific techniques and treatment course are outlined to demonstrate the model offered as one meeting the unique needs of the pediatric survivor. This model emphasizes a behavioral, individually tailored approach with clear delineation of a functional academic skill goal of competence in mathematical computation. Results indicate accomplishment of goals and some generalization of skills obtained to a math domain that was not the major focus of the remediation attempts. PMID- 1744810 TI - The children's eating behavior inventory: reliability and validity results. AB - Eating and mealtime problems are common in childhood. They occur across a broad age span, in normally developing children and in a wide variety of developmental and medical disorders. There is no currently available standard instrument by which to assess these problems. The Children's Eating Behavior Inventory (CEBI) was developed according to a conceptual framework based upon a transactional/systemic understanding of parent-child relationships. It was completed by 206 mothers of nonclinic children and 110 mothers of clinic children. Results of test-retest and internal reliability testing indicate that the CEBI meets criteria for instrument reliability. Construct validity is demonstrated by the significant difference between the clinic and nonclinic groups in the mean total eating problem score and in the mean number of items perceived to be a problem. PMID- 1744811 TI - Sickle cell disease in children and adolescents: the relation of child and parent pain coping strategies to adjustment. AB - Examined pain coping strategies in 72 children and adolescents with sickle cell disease and their parents using the Coping Strategies Questionnaire, and found that pain coping strategies could be reliably assessed. Children high on Negative Thinking and Passive Adherence were less active, required more health care services, and were more psychologically distressed during painful episodes. Children high on Coping Attempts were more active and required less frequent health care services. Parents high on Coping Attempts and low on Passive Adherence had children who were more active. PMID- 1744812 TI - Athermal effects of microwaves. PMID- 1744813 TI - "A perspective on 'athermal' effects". PMID- 1744814 TI - Microwave blood plasma defroster. AB - A microwave blood plasma defroster capable of thawing up to four bags of frozen blood plasma at a time is described. The unit stops automatically when the plasma reaches a preset temperature, and all operating parameters are monitored for safety. Comparative testing showed that blood plasma thawed in this device was indistinguishable from plasma thawed in a water bath. PMID- 1744815 TI - Programmable sweep radiometer system as a new tool for non-invasive thermometry. AB - A new microwave radiometer system consisting of a frequency sweep-type radiometer and an ultra wideband antenna has been developed. A computer-controlled radiometer system covers the input frequency range from 0.5 GHz to 8 GHz. It can be used not only as a multispectral radiometer system whose frequencies can be chosen freely, but also as a frequency sweep-type radiometer system whose frequency is continuously swept during measurement. When an antenna is attached to a forearm, the sensitivity of the radiometer system exceeds 0.09 degree C when the integration time is 3 sec and IF bandwidth is 500 MHz. The new microwave radiometer system may be utilized for non-invasive thermometry of the human body. PMID- 1744816 TI - On the role of 26-deoxylaidlomycin in laidlomycin biosynthesis. AB - 3H-26-deoxylaidlomycin (I) was fed to growing cultures of Streptoverticillium olivoreticuli IMET 43782 producing both I and laidlomycin (II). The incorporation of labelled I into laidlomycin II was neglible showing a role of I as precursor of II to be at variance. Otherwise, a measurable conversion was achieved by the use of sonicated 48 hrs mycelium suggesting that final oxidation of I to II could be mediated by a compartmentized oxidoreductase. PMID- 1744817 TI - Analysis of extrinsic factor associated with 379 injuries occurring during 34,236 military parachute descents. AB - A retrospective study of 34,236 consecutive static line parachute descents by trained parachutists, in which 379 were injured, is described. Injury rates associated with extrinsic factors were compared and then analyzed using logistic regression. A table describing the association with extrinsic factors, with relative risks, is at Annex A. The overall injury rate was 1.11% (1.11 injured per 100 descents). Rates from Helicopter (0.20%) and Balloon (0.13%) were low, and the study thus concentrated on aeroplane descents (injury rate 1.46%). Extrinsic factors associated with increased injury rates were carriage of equipment; wind speed and direction; numbers exiting and (on logistic regression) night descents. The overall rates appear higher than expected, possibly due to equipment weight potentiating the other factors. A prospective study is required to investigate the effect of equipment weight after which peace time training constraints should be reviewed. (Two approaches are described.) PMID- 1744818 TI - The epidemiology of snake bite presenting to British Military Hospital Dharan during 1989. AB - Fifty-eight cases of snake bite seen at the British Military Hospital, Dharan, Nepal during 1989 were studied prospectively. Data is presented on the epidemiology and outcome of snake bite in this area of lowland Nepal with details of the age and sex of patients, date and time of bite, delay in arrival at hospital, use of tourniquets, circumstances of the bite, and snake identification. Neurotoxicity due to envenomation was recorded in 11 patients. No case of coagulopathy was recorded. The overall case fatality was 5.2% but mortality amongst those exhibiting signs of neurotoxicity was 27.3%. PMID- 1744819 TI - Community acquired pneumonia in the Gulf. PMID- 1744820 TI - A study into loss of consciousness. AB - The case notes of patients admitted with loss of consciousness (LOC) to BMH Rinteln over 18 months were retrospectively studied. Forty percent of those diagnosed as epileptic were heavy goods vehicle (HGV) drivers. This paper audits the criteria for diagnosis and discusses its implications on the soldier's career. PMID- 1744821 TI - Trauma care in a military hospital. AB - The results of a quinquennial audit of trauma care in the Cambridge Military Hospital using the TRISS method is presented. 113 cases were analysed. The mean age was 32 years and the mean Injury Severity Score 16. Twenty-five deaths occurred of which 12 were potentially preventable. Means of reducing the number of preventable deaths are discussed. PMID- 1744822 TI - Stone fish and stingrays--some notes on the injuries that they cause to man. AB - A review is presented of past and present records of injuries caused by these fish with particular reference to the occasional fatalities that have ensued. The wide geographical range of species of both types indicate a variety of current Service postings where such injuries can be sustained. The pharmacological actions of the venoms of both types are summarised as far as they are known. Modern lines of management are described which stress the need for thorough debridement of these injuries. PMID- 1744823 TI - A simple method of isolated digital exsanguination. PMID- 1744824 TI - A mobile anaesthetic--rapid evacuation from hospital. AB - The use of the Triservice Anaesthetic Apparatus for the emergency evacuation of an anaesthetised patient from nuclear, biological and chemical (NBC) collective protection in a tented hospital complex in the Gulf is described. Because of its compact size and portability the Triservice Anaesthetic Apparatus may prove to be ideal for use in emergency evacuation. PMID- 1744825 TI - Traumatic rupture of bicepts brachii--a hazard of military parachuting. AB - Closed traumatic rupture of the biceps brachii has not been reported occurring to a British military parachutist. This paper describes such an injury to a British military parachutist using United States (US) Army equipment and procedures. The discussion highlights differences between British Army and US Army equipment and procedures which make the chances of this injury occurring to a British paratrooper very small. PMID- 1744826 TI - Trans-radial styloid, trans-scaphoid, trans-triquetral perilunate dislocation. AB - A rare case of trans-radial styloid, trans-scaphoid, trans-triquetral perilunate dislocation is described. The injury was treated by reduction and internal fixation using a Herbert screw and Kirschner wire. A good functional result was achieved. A review of the literature illustrates that early surgery is recommended. Alternative surgical approaches are discussed. PMID- 1744827 TI - West African malaria. AB - Plasmodium falciparum malaria poses an increasing risk to travellers to West Africa. The development of chloroquine resistant in West Africa has further compounded the risk. Two cases of falciparum malaria from Sierra Leone are presented. One represents the classic missed case and the other a probable case of chloroquine resistant (RI vide infra) falciparum malaria. These cases highlight the danger of the missed or late diagnosis; the need for chemoprophylaxis, even in emigrants; the threat posed to the international traveller by malaria; and the problem of chloroquine resistant Plasmodium falciparum (CRPF) malaria from West Africa. The position of Plasmodium falciparum malaria in West Africa is reviewed along with the problem caused by chloroquine resistance. PMID- 1744828 TI - Oesophageal spasm as a side effect of nerve agent pre-treatment system. PMID- 1744829 TI - Pilonidal sinus in an amputee. PMID- 1744830 TI - Future of the Army medical services. PMID- 1744831 TI - Scavenging from the triservice anaesthetic apparatus (TSA) PMID- 1744832 TI - Warming intravenous fluids. PMID- 1744833 TI - Ethics, economics and science. PMID- 1744834 TI - 'Cardiogenic dementia' revisited. PMID- 1744835 TI - Metchnikoff revisited. PMID- 1744836 TI - Otitis media and its sequelae. PMID- 1744837 TI - Hearing loss in chronic renal failure-hearing threshold changes following haemodialysis. AB - The prevalence of sensorineural hearing loss, measured by pure tone audiometry, was determined in 66 patients with chronic renal failure and threshold changes following haemodialysis were measured in 31 patients. The incidence of hearing loss was 41% in the low, 15% in the middle and 53% in the high frequency ranges respectively. No correlations with weight changes, haematocrit, metabolic bone disease or ototoxic drug history were found. Of 62 ears studied, 38% had a decrease in low frequency threshold after dialysis and 9% had an increase. Threshold in 22/31 ears with pre-existing low frequency loss altered after dialysis with little change in other frequencies and no correlation with weight changes. In conclusion, we find a high incidence of low and high frequency hearing losses in chronic renal failure patients. Fluctuation in low frequencies with dialysis is common. Possible mechanisms include treatment induced changes in fluid and electrolyte composition of endolymph. PMID- 1744838 TI - Open access exercise electrocardiography: a service to improve management of ischaemic heart disease by general practitioners. AB - An initial study of the use of open access exercise electrocardiography by general practitioners (GPs) in South East Kent showed that patient selection and interpretation of test results was frequently incorrect. After issuing guidelines, modifying the request form and instituting registrar review of all requests, significant improvements in both referral pattern, result interpretation and patient management have resulted. Forty-nine GPs requested 110 exercise tests during 1988/89. Twelve per cent were not undertaken after discussion with the referring practitioner. Eighty-four per cent of those tested would have been referred to the district general hospital cardiology outpatient department in the absence of open access exercise electrocardiography service. Six per cent of patients were referred directly for invasive investigation. Thirty-five per cent were referred to the district general hospital cardiology outpatient department, whilst 42% were spared hospital referral based on the result of the investigation. Better use of the modified service was suggested by: referral of fewer patients with non-cardiac chest pains (P = 0.002); more patients with a moderate pre-test probability of ischaemic heart disease (P less than 0.05); fewer inappropriate requests (P less than 0.01); and fewer inappropriately undertaken tests (P less than 0.001) than in the previous study. All patients with strongly positive test results were appropriately managed. Open access exercise electrocardiography in the format investigated is potentially a cost-effective and useful tool to improve diagnosis and management of heart disease by GPs. PMID- 1744839 TI - Patients learning from each other: self-help groups for people with diabetes. PMID- 1744840 TI - Accuracy of reagent strip testing for urinary tract infection in the elderly. AB - The accuracy of reagent strip testing for urinary tract infection (UTI) was assessed in 100 elderly patients (50 acute patients admitted to hospital and 50 attending the day hospital). Reagent strip sensitivities were: acute patients urinary nitrite 83%, blood 67%, protein 72% and leucocytes 72%, and day hospital patients-urinary nitrite 90%, blood 65%, protein 30% and leucocytes 60%. Urinary nitrite specificities were 100% for both groups of patients. Only 28% of patients with a UTI had specific symptoms of the infection; pyrexia and a raised WBC also proved poor indicators. Urinary nitrite was thus the most accurate immediate indicator of UTI. PMID- 1744841 TI - Conserving blood in preparation for elective surgery. AB - A prospective study was carried out for a period of 6 months (September 1987 to 28 February 1988) to evaluate the possible misuse of blood transfusion service in the department of surgery, Amiri Teaching Hospital, Kuwait. There was a monthly wastage of 45 +/- 13 units of blood. Five hundred and eleven units of blood were crossmatched but never transfused. The time taken by the blood bank technicians in crossmatching blood which was never used amounted to 54.4% of the normal working hours. An annual loss of about US$25000.00 was calculated to have occurred. PMID- 1744842 TI - Frankincense and myrrh as remedies in children. AB - Two cases of therapy with frankincense and myrrh in children are presented. The long history of this unusual treatment is outlined, demonstrating that for several millenia such agents have been employed in a number of medical contexts, as well as in the perfume and incense industries. Myrrh has found recent pharmacological application in the reduction of cholesterol and triglycerides, as predicted by several traditional therapies. PMID- 1744843 TI - Observations on the intrinsic blood supply to the human patella: disruption correlated with articular surface degeneration. AB - The intrinsic blood supplies of 13 human patellae with varying degrees of articular surface degeneration were studied by perfusion techniques. Disruption of the normal pattern of arterial arcades correlated with increasing surface wear. PMID- 1744844 TI - Role of drugs and alcohol in patients with head injury. AB - In an effort to define the role that substance abuse has to play in head injuries, a prospective study of 204 patients presenting to the Accident and Emergency (A&E) Department over a 10-week period was carried out. Urine samples were collected and assayed for the presence of common drugs of abuse and alcohol. One or other substance (drugs or alcohol) was detected in 43% of patients. The association between alcohol and head injuries has been confirmed and the importance of drugs in this area has been addressed and found to be of some significance. More rapid and accurate methods of assaying these substances may improve our management of head injury patients. PMID- 1744845 TI - Postoperative fluid therapy--put not thy faith in dextrose saline: discussion paper. PMID- 1744846 TI - Long-term difficult-to-manage patients--their need for continuity of care: discussion paper. PMID- 1744847 TI - Angiodysplasia: a review. PMID- 1744848 TI - Lucja Frey and the auriculotemporal nerve syndrome. PMID- 1744849 TI - From blood pressure to hypertension: the history of research. PMID- 1744850 TI - Unilateral choanal atresia. PMID- 1744851 TI - Blastocystis hominis complicating ulcerative colitis. PMID- 1744852 TI - Successful treatment of neonatal purpura fulminans with epoprostenol. PMID- 1744853 TI - Reversal of cognitive deficit by cardiac pacing in a young man with dystrophia myotonica. PMID- 1744854 TI - Bilateral internuclear ophthalmoplegia as a false localizing sign. PMID- 1744855 TI - Acquired C1-inhibitor deficiency preceding malignant lymphoma by 7 years. PMID- 1744856 TI - Moraxella lacunata infectious arthritis. PMID- 1744857 TI - Lead poisoning due to Asian ethnic treatment for impotence. PMID- 1744858 TI - Medical helicopter systems. PMID- 1744859 TI - The war on cancer. PMID- 1744860 TI - Myalgic encephalomyelitis. PMID- 1744861 TI - Surgeons and the risk of contamination during operations. PMID- 1744862 TI - Pathology; is it well taught? PMID- 1744863 TI - The Coma report: sugars and dental caries. PMID- 1744864 TI - Haemorheological treatment of ischaemia--facts or fancy? PMID- 1744865 TI - What is the best dosage schedule for patients? PMID- 1744866 TI - The police doctor in and out of court--a view from the bench. PMID- 1744867 TI - A novel approach to anxiolytic premedication for day-case patients. AB - The usefulness of 10 mg timolol orally as a non-sedative anxiolytic premedicant for day-case patients was examined in a double-blind placebo-controlled study. Patients were invited to take part by letter sent the week before gynaecological (n = 40) or oral (n = 60) surgery was scheduled. Indices of anxiety and alertness were obtained prior to administration of the tablet; quality of previous anaesthetic experience was also recorded. In those patients with no previous or unpleasant previous anaesthetic experience a significant reduction in anxiety amongst those given timolol was identified. Haemodynamic differences between the groups were not clinically significant, and return of psychomotor function was not delayed by timolol. Timolol effectively reduces situational anxiety, is non sedative, and is advocated as a premedicant for anxious day-case patients and others in whom rapid return of psychomotor function is desirable. PMID- 1744868 TI - Low dose botulinum toxin in spasmodic torticollis. AB - Botulinum toxin has been successfully used to treat spasmodic torticollis. The optimum dosage is not clear and the recommended doses in the United Kingdom are 20-25 ng. We have used much lower doses (average 13 ng) without loss of efficacy and accompanied by a reduction in side effects. We treated 12 patients (eight women and four men) with a mean duration of torticollis of 4 years. Eleven of the 12 patients (91%) showed an improvement in total scores for pain and degree of head movement. The benefits appeared a week after treatment and lasted for 3 months. Side effects were minimal and transient. Our experience suggests low doses of the toxin may be equally efficacious. PMID- 1744869 TI - Impact of an extensive in situ component on the presence of residual disease in screen detected breast cancer. AB - This study investigates the histopathological characteristics of a consecutive series of 100 screen detected breast cancers in relation to residual disease. Tumour type, size, grade, resection margins and extent of primary or associated in situ disease were all assessed by one pathologist. Thirty-seven women underwent further surgery (wider excision or mastectomy) and the resected specimen was examined for residual in situ or invasive cancer. In total, 36 cancers had an extensive in situ component, of which 69% were predominantly intraduct carcinoma of comedo type. Of the 37 women who underwent further resection, 21 (57%) women had residual cancer. Of those with initial disease at the resection margin, 16/25 (64%) had residual disease. Five of 12 (42%) with disease close to (within 2-3 mm) but not at the margin had residual disease. Of those with an extensive in situ component, 18/25 (72%) had residual disease, whereas only 2/12 (17%) women with none or some in situ disease had residual cancer. In screen detected breast cancer, residual cancer was present in 72% of women with an extensive in situ component at initial surgery. These women comprise a group in which conservation surgery may be inappropriate if completeness of excision is considered a prerequisite for breast conserving surgery. PMID- 1744870 TI - Rape and sexually transmitted diseases: patterns of referral and incidence in a department of genitourinary medicine. AB - A retrospective study was carried out of all women attending a Department of Genitourinary Medicine over a 3-year period. Note was taken of referring source, presenting symptoms, infection detected at STD screening and follow-up attendance. Comparison was also made between the number of women referred by the police surgeon and the number who actually attended. We observed an overall incidence of STD of 35% and noted that many infections had a similar prevalence to that of our normal clinic population over the same time period. Only 13% of the women referred by the police attended although after the initial visit attendance was similar regardless of referral source. A number of asymptomatic women were noted to have infection with Neisseria gonorrhoeae and Chlamydia trachomatis. Although, the risk of significant STD following sexual assault is low greater efforts should be made to encourage women to attend for screening whether or not they are symptomatic. PMID- 1744871 TI - Do routine clinic visits prevent de-stabilization in patients awaiting coronary revascularization? AB - We examined retrospectively the usefulness of routine clinic visits in preventing adverse cardiac events in 115 patients awaiting coronary surgery or angioplasty. Mean waiting time from angiography to revascularization was 126 days. A total of 126 visits were made by 80 patients. No deaths occurred, but one patient, despite three visits, suffered myocardial infarction at 316 days post-angiography. Eight patients required admission for unstable angina, five having been on the waiting list for less than 5 weeks. The mean number of clinic visits, number of diseased vessels and proportion on triple anti-ischaemic therapy were similar in the patients suffering such events and those remaining stable. In conclusion, the inherent unpredictability of coronary disease greatly limits the role of interim clinic visits in the prevention of adverse cardiac events in patients awaiting revascularization. PMID- 1744872 TI - Can outpatient non-attendance be predicted from the referral letter? An audit of default at neurology clinics. AB - Data obtained from new patient referral letters to regional and peripheral neurology clinics were studied prospectively over a 6-month period in an attempt to determine factors predicting non-attendance. Attendance at peripheral clinics was significantly better, confirming their value. At regional clinics, factors associated with non-attendance were male sex, patient age less than 50 years, urban home address, referral from Accident and Emergency Departments, symptom duration less than 12 months, and wait for appointment more than 2 months. Of these, referral source and waiting time were identified as factors which could be modified, confirming that this analysis of referral letters was a useful exercise. PMID- 1744873 TI - Management of generalized faecal peritonitis--can we do better? AB - Generalized faecal peritonitis is associated with a mortality of over 50% in most series of cases. Despite great improvements in the standards of intensive care the morbidity and mortality associated with this condition have not improved, in part due to recurrent intra-abdominal sepsis. This preliminary study investigated the role of laparotomy, repeated abdominal lavage and debridement to determine whether such a policy might lead to an improvement in outcome. Of six cases studied three had perforated diverticular disease, two had Crohn's disease. Twenty lavages were performed on these six patients who had a mean ICU stay of 8 days. Five out of the six patients left hospital and remain well, one patient died of septicaemia and pre-existing renal failure. This study found that laparotomy, repeated abdominal lavage and debridement may be effective in reducing the morbidity and mortality of generalized faecal peritonitis and further study of this technique is appropriate. PMID- 1744874 TI - Use of an antibacterial powder spray to prevent post prostatectomy urinary infection. AB - To prevent ascending urinary infection in patients following transurethral prostatectomy, we have studied the use of a topical antibacterial agent applied to the groin and external genitalia. A prospective randomized controlled trial was conducted, with 50 patients being treated by daily application of a 2% polynoxylin powder, and 50 patients acting as untreated controls. Patient age and duration of catheterization were similar in the treated and untreated groups. No significant benefit was seen in the treated cohort (P greater than 0.05) in terms of reduction in postoperative urinary infection. PMID- 1744875 TI - Gut fermentation: a reappraisal of an old clinical condition with diagnostic tests and management: discussion paper. PMID- 1744876 TI - Some observations of George James Guthrie on gunshot wounds of the thigh during the Crimean War (1854-1855). PMID- 1744877 TI - 'Medium red with fresh fruity nose ...': doctors and viniculture in 19th century Australia. PMID- 1744878 TI - London's last private medical school. PMID- 1744879 TI - Angiocentric T-cell lymphoma in skin. PMID- 1744880 TI - Cutaneous extension of Hodgkin's disease. PMID- 1744881 TI - Haemoptysis after Dwyer instrumentation for idiopathic scoliosis. PMID- 1744882 TI - Computed tomography as an aid to diagnosis of early pulmonary actinomycosis. PMID- 1744883 TI - Lightning strike and autonomic failure--coincidence or causally related? PMID- 1744884 TI - Hypothyroidism and renal impairment. PMID- 1744885 TI - Spontaneous rupture of the oesophagus (Boerhaave's syndrome): conservative versus surgical management. PMID- 1744886 TI - Family therapy for anorexia nervosa--why not? PMID- 1744887 TI - Spontaneous adverse drug reaction reports. PMID- 1744888 TI - Pathology: is it well taught? PMID- 1744889 TI - Crohn's disease of the vulva. PMID- 1744890 TI - Falls in the elderly. PMID- 1744891 TI - Honey and healing of leg ulcers. PMID- 1744892 TI - Lipids in non-insulin dependent diabetes: a case for treatment? PMID- 1744893 TI - Value of emergency cardiac enzymes. PMID- 1744894 TI - Anal cancer: the case for earlier diagnosis. PMID- 1744895 TI - Medical malpractice crisis. PMID- 1744896 TI - Superior oblique palsy following ethmoidal surgery. PMID- 1744897 TI - Circumcision and sand. PMID- 1744898 TI - Protecting the index finger during surgery. PMID- 1744899 TI - Conformational changes in human red cell membrane proteins induced by sugar binding. AB - We have previously shown that the human red cell glucose transport protein and the anion exchange protein, band 3, are in close enough contact that information can be transmitted from the glucose transport protein to band 3. The present experiments were designed to show whether information could be transferred in the reverse direction, using changes in tryptophan fluorescence to report on the conformation of the glucose transport protein. To see whether tryptophan fluorescence changes could be attributed to the glucose transport protein, we based our experiments on procedures used by Helgerson and Carruthers [Helgerson, A. L., Carruthers, A., (1987) J. Biol. Chem. 262:5464-5475] to displace cytochalasin B (CB), the specific D-glucose transport inhibitor, from its binding site on the inside face of the glucose transport protein, and we showed that these procedures modified tryptophan fluorescence. Addition of 75 mM maltose, a nontransportable disaccharide which also displaces CB, caused a time-dependent biphasic enhancement of tryptophan fluorescence in fresh red cells, which was modulated by the specific anion exchange inhibitor, DBDS (4,4'-dibenzamido-2,2' stilbene disulfonate). In a study of nine additional disaccharides, we found that both biphasic kinetics and DBDS effects depended upon specific disaccharide conformation, indicating that these two effects could be attributed to a site sensitive to sugar conformation. Long term (800 sec) experiments revealed that maltose binding (+/- DBDS) caused a sustained damped anharmonic oscillation extending over the entire 800 sec observation period. Mathematical analysis of the temperature dependence of these oscillations showed that 2 microM DBDS increased the damping term activation energy, 9.5 +/- 2.8 kcal mol-1 deg-1, by a factor of four to 39.7 +/- 5.1 kcal mol-1 deg-1, providing strong support for the view that signalling between the glucose transport protein and band 3 goes in both directions. PMID- 1744900 TI - Diversity of K+ channels in the basolateral membrane of resting Necturus oxyntic cells. AB - Patch-clamp techniques have been applied to characterize the channels in the basolateral membrane of resting (cimetidine-treated, nonacid secreting) oxyntic cells isolated from the gastric mucosa of Necturus maculosa. In cell-attached patches with pipette solution containing 100 mM KCl, four major classes of K+ channels can be distinguished on the basis of their kinetic behavior and conductance: (1) 40% of the patches contained either voltage-independent (a) or hyperpolarization-activated (b), inward-rectifying channels with short mean open times (16 msec for a, and 8 msec for b). Some channels showed subconductance levels. The maximal inward conductance gmax was 31 +/- 5 pS (n = 13) and the reversal potential Erev was at Vp = -34 +/- 6 mV (n = 9). (2) 10% of the patches contained depolarization-activated and inward-rectifying channels with gmax = 40 +/- 18 pS (n = 3) and Erev was at Vp = -31 +/- 5 mV (n = 3). With hyperpolarization, the channels open in bursts with rapid flickerings within bursts. Addition of carbachol (1 mM) to the bath solution in cell-attached patches increased the open probability Po of these channels. (3) 10% of the patches contained voltage-independent inward-rectifying channels with gmax = 21 +/- 3 pS (n = 4) and Erev was at Vp = -24 +/- 9 mV (n = 4). These channels exhibited very high open probability (Po = 0.9) and long mean open time (1.6 sec) at the resting potential. (4) 20% of the patches contained voltage-independent channels with limiting inward conductance of 26 +/- 2 pS (n = 3) and Erev at Vp = -33 +/- 3 mV (n = 3). The channels opened in bursts consisting of sequential activation of multiple channels with very brief mean open times (10 msec). In addition, channels with conductances less than 6 pS were observed in 20% of the patches. In all nine experiments with K+ in the pipette solution replaced by Na+, unitary currents were outward, and inward currents were observed only for large hyperpolarizing potentials. This indicates that the channels are more selective for K+ over Na+ and Cl-. A variety of K+ channels contributes to the basolateral K+ conductance of resting oxyntic cells. PMID- 1744901 TI - Response of chloride efflux from skeletal muscle of Rana pipiens to changes of temperature and membrane potential and diethylpyrocarbonate treatment. AB - Efflux of 36Cl- from frog sartorius muscles equilibrated in two depolarizing solutions was measured. Cl- efflux consists of a component present at low pH and a pH-dependent component which increases as external pH increases. For temperatures between 0 and 20 degrees C, the measured activation energy is 7.5 kcal/mol for Cl- efflux at pH 5 and 12.6 kcal/mol for the pH-dependent Cl- efflux. The pH-dependent Cl-efflux can be described by the relation mu = 1/(1 + 10n(pK alpha-pH], where mu is the Cl- efflux increment obtained on stepping from pH 5 to the test pH, normalized with respect to the increment obtained on stepping from pH 5 to 8.5 or 9.0. For muscles equilibrated in solutions containing 150 mM KCl plus 120 mM NaCl (internal potential about -15 mV), the apparent pK alpha is 6.5 at both 0 and 20 degrees C, and n = 2.5 for 0 degrees C and 1.5 for 20 degrees C. For muscles equilibrated in solutions containing 7.5 mM KCl plus 120 mM NaCl (internal potential about -65 mV), the apparent pK alpha at 0 degrees C is 6.9 and n is 1.5. The voltage dependence of the apparent pK alpha suggests that the critical pH-sensitive moiety producing the pH-dependent Cl- efflux is sensitive to the membrane electric field, while the insensitivity to temperature suggests that the apparent heat of ionization of this moiety is zero. The fact that n is greater than 1 suggests that cooperativity between pH sensitive moieties is involved in determining the Cl- efflux increment on raising external pH. The histidine-modifying reagent diethylpyrocarbonate (DEPC) applied at pH 6 reduces the pH-dependent Cl- efflux according to the relation, efflux = exp(-k.[DEPC].t), where t is the exposure time (min) to DEPC at a prepared initial concentration of [DEPC] (mM). At 17 degrees C, k-1 = 188 mM . min. For temperatures between 10 and 23 degrees C, k has an apparent Q10 of 2.5. The Cl- efflux inhibitor SCN- at a concentration of 20 mM substantially retards the reduction of the pH-dependent Cl- efflux by DEPC. The findings that the apparent pK alpha is 6.5 in depolarized muscles, that DEPC eliminates the pH-dependent Cl- efflux, and that this action is retarded by SCN- supports the notion that protonation of histidine groups associated with Cl- channels is the controlling reaction for the pH-dependent Cl- efflux. PMID- 1744902 TI - Characterization of BADS-binding proteins in epithelial plasma membranes. AB - When a fluorescent stilbene was added to epithelial plasma membrane suspension the emission spectrum showed a broad peak containing overlapping emissions resulting from different adducts. By focusing on a specific emission wavelength a common site having a dissociation constant of approximately 5 microM was calculated in the rat kidney, small intestine, pancreatic islets and shark rectal gland. This binding could be displaced by loop diuretics, (e.g., furosemide with an IC50 of 40 microM), DIDS (ki 1 microM) and thiocyanate. These results pose certain questions such as: (i) whether the evidence for multiple peaks are due to specific interactions representing multiple binding affinities and (ii) whether the binding of stilbene and the observed displacement can be identified on a specific protein. Separating the proteins present in the purified basolateral and brush-border membranes by SDS-PAGE, transfer of these proteins onto nitrocellulose paper and labeling of the nitrocellulose strips by radioactive BADS (4-benzamido-4'aminostilbene-2-2'disulphonic acid) and bumetanide could identify labeled proteins. These experiments showed that whereas some proteins bound either BADS or bumetanide, one protein with a molecular weight of approximately 100 or 130,000 D appeared to bind both. This protein was found on the basolateral membrane in the rat kidney cortex and medulla and the shark rectal gland and in the basolateral and brush-border membranes of the small intestine. Displacement of the protein-bound stilbene by loop diuretics could not be quantitated on the nitrocellulose transfer strips for this protein. Antibodies raised against the cytoplasmic fragment of band 3 reacted with the stilbene labeled 100-130,000 D proteins indicating sufficient immuno-cross-reactivity between the separate species. These experiments involving binding of BADS and bumetanide and cross-reactivity with the human band 3 antibody suggest that these kilodalton proteins could structurally resemble human band 3. PMID- 1744903 TI - Sodium-dependent L-serine transport in plasma membrane vesicles isolated from Ehrlich cells by two-phase compartmentation. AB - Plasma membrane vesicles were prepared from Ehrlich cells using two-phase system compartmentation. The highly pure plasma membrane vesicles obtained presented a negligible mitochondrial contamination and were suitable for studies of amino acid transport. L-Serine transport showed a clear ionic specificity, maximum incorporation being observed when an inwardly directed NaSCN gradient was used. Na(+)-dependent L-serine transport was dependent on assay temperature and membrane potential, and it seemed to be carried out by two different transport systems. An essential sulfhydryl group seemed to be involved in the transport process. PMID- 1744904 TI - Ba(2+)-induced action potentials in osteoblastic cells. AB - Trains of long-duration "action potentials" were induced by Ba2+ in osteoblast like rat osteosarcoma cells (ROS 17/2.8), under current clamp and voltage clamp. Large depolarizing pulses were seen in microelectrode measurements at 37 degrees C following the addition of 10 or 20 mM Ba2+ to physiological bathing medium. Application of BAY K 8644 resulted in the onset of the pulses at earlier times and at more negative potentials. The pulses were blocked by nifedipine and Cd2+, but not by Ni2+. Large inward current pulses were seen in whole-cell patch technique voltage-clamp measurements at 37 degrees C in the presence of from 10 to 110 mM Ba2+ in the bathing medium. The current pulses were not seen at 22 degrees C in the presence of 110 mM Ba2+, but could be induced by BAY K 8644. These pulses were not blocked by TTX, but were blocked by nifedipine, Cd2+, Zn2+, Co2+, and by an increase in bathing [Ca2+]. The shape and frequency of the current pulses were the same as for voltage pulses under current clamp. A model that can explain these observations involves opening of L-type Ca2+ channels in a voltage-independent manner by cytosolic Ba2+ via a screening of Ca2+ from sites that produce either inactivation or a lower probability of opening in the activated state. There would be a closing of these channels at higher [Ba2+] as Ba2+ is forced onto these sites. A refractory period is also required to give repeated pulses of openings. PMID- 1744905 TI - Characterization of constitutive exocytosis in the yeast Saccharomyces cerevisiae. AB - Constitutive exocytosis was investigated in the yeast Saccharomyces cerevisiae using temperature-sensitive mutant (sec) strains which do not allow vesicle fusion to the plasma membrane at the restrictive temperature. Secretory vesicles were accumulated in the cell at the restrictive temperature and then protein synthesis was blocked with cycloheximide. Upon returning the cells to the permissive temperature the contents of the accumulated vesicles were secreted. This allowed the study of constitutive exocytosis independent of the processes responsible for vesicular biosynthesis. Neither the kinetics nor magnitude of exocytosis were affected by removal of external Ca2+ or perturbations of cytosolic Ca2+. This suggests that in those systems where calcium is required for exocytosis it is a regulatory molecule and not part of the mechanism of membrane fusion. Release occurred over a very broad range of pH and in media with different ionic compositions, suggesting that ionic and potential gradients across the plasma membrane play no role in exocytosis in yeast. High osmolarity inhibited the rate, but not the extent, of release. A novel inhibitory effect of azide was detected which occurred only at low pH. Vanadate also inhibited release in a pH-independent manner. Secretion occurred at the same rate in cells with or without accumulated vesicles. This infers a rate-limiting step following vesicle accumulation, perhaps a limiting number of release sites on the plasma membrane. PMID- 1744906 TI - Activation of osmolyte efflux from cultured renal papillary epithelial cells. AB - The rabbit renal papillary epithelial cell line PAP-HT25 accumulates sorbitol and other organic osmolytes when cultured in hypertonic media. When returned to isotonic media, PAP-HT25 cells swell because of water influx and then shrink to their normal volume because of rapid osmolyte and water efflux (volume regulatory decrease, VRD). Sorbitol efflux from PAP-HT25 cells during VRD was reduced to 18% of control by incubation of the cells with 100 microM eicosatetraynoic acid (ETYA), indicating that an enzyme that metabolizes arachidonic acid (AA) is a key component of the efflux process. Sorbitol efflux was unaffected by incubation with cyclooxygenase and lipoxygenase inhibitors but was reduced to 9% by incubation with 100 microM ketoconazole and to 37% by incubation with 100 microM SKF-525A, indicating that the cytochrome P-450 limb of the AA cascade is involved in the efflux process. The efflux of other organic osmolytes betaine and myoinositol, but not glycerolphosphorylcholine, was also inhibited by incubation with ETYA and ketoconazole. PMID- 1744907 TI - Major myelin proteolipid: the 4-alpha-helix topology. PMID- 1744908 TI - AIDS-related health behavior: coping, protection motivation, and previous behavior. AB - The purpose of this study was to examine Rogers' protection motivation theory and aspects of Janis and Mann's conflict theory in the context of AIDS-related health behavior. Subjects were 84 heterosexual men and women and 147 homosexual men with multiple sexual partners; LISREL's path-analysis techniques were used to evaluate the goodness of fit of the structural equation models. Protection motivation theory did fit the data but had considerably more explanatory power for heterosexual than for homosexual subjects (49 vs. 22%, respectively). When coping styles were added, different patterns of findings were found among both groups. Adding variables such as social norms and previous behavior increased the explained variance to 73% for heterosexual subjects and to 44% for homosexual subjects. It was concluded that although protection motivation theory did fit the data fairly adequately, expanding the theory with other variables--especially those related to previous behavior--could improve our understanding of AIDS related health behavior. PMID- 1744909 TI - Relaxation, reduction in angry articulated thoughts, and improvements in borderline hypertension and heart rate. AB - An intensive 7-week relaxation therapy was evaluated in a sample of unmedicated borderline hypertensive men. All subjects were provided state-of-the-art medical information regarding changes known to affect hypertension favorably, e.g., lower salt intake and regular exercise. In addition, relaxation subjects were trained in muscle relaxation that entailed audiotaped home practice. As predicted, relaxation combined with hygiene lowered blood pressure more than did hygiene alone. Neither treatment favorably affected a paper-and-pencil measure of anger but relaxation did lower anger-hostility on a new cognitive assessment procedure, Articulated Thoughts in Simulated Situations (ATSS). Moreover, ATSS anger hostility reduction was correlated with blood pressure or heart rate reductions, for all subjects and especially for those in the Relaxation condition. This represents the first clinically demonstrated link between change in a cognitive variable and change in cardiovascular activity. Finally, results were especially strong in subjects high in norepinephrine, suggesting its importance in essential hypertension. PMID- 1744910 TI - A comparison of hormone therapy, coping skills training, and relaxation for the relief of premenstrual syndrome. AB - Approximately 10% of women are severely affected by premenstrual syndrome (PMS) during their reproductive years. Several biological theories of causation have been proposed and each has provoked treatment attempts through medication to little sustained effect. As many of the reported complaints are psychological, a new treatment approach was considered using cognitive-behavioral therapy. A preliminary study which combined cognitive-behavioral therapy with drug treatment produced considerable symptom reduction. The present study examined the efficacy of cognitive-behavioral therapy alone in direct comparison with hormone treatment. Relaxation instructions were provided to a control group. Initial rapid responses to drug treatment and relaxation diminishes after 2 months, together with marked attrition in the control group. Significant positive benefits from cognitive-behavioral therapy were achieved after the first treatment month that continued throughout and were maintained at follow-up 3 months later. Implications for future management are discussed. PMID- 1744911 TI - When does a choice of coping strategies help? The interaction of choice and locus of control. AB - Undergraduate student volunteers either were given a choice of coping strategies or were assigned to a coping strategy which was used to help them tolerate the cold pressor. Subjects who were given a choice of coping strategies reported their strategy to be more credible and perceived a greater sense of control than subjects who were not given a choice. Improved pain tolerance, however, did not result directly from being given a choice. Increases in pain tolerance depended on locus of control. Subjects who had a high internal health locus of control reported a greater strength of self-efficacy and demonstrated increased pain tolerance following a choice of strategies. In comparison, subjects who reported a more external health locus of control did not benefit from receiving a choice. This study has implications for our understanding of the role of choice in therapy and for improving the effectiveness of our interventions with individuals. PMID- 1744912 TI - Perceived health problems in subjects with varying cardiovascular diagnoses. AB - To study perceived health problems in subjects with differing cardiovascular status, the Nottingham Health Profile (NHP) was administered to 210 subjects 55 years of age and over. Subjects were categorized as being cardiovascular "Normals," being hypertensive, having isolated coronary artery disease, or both being hypertensive and having coronary artery disease. An analysis of variance between the four cardiovascular strata on each of the six subscales of the NHP yielded significant differences between the groups on the subscales Pain, Physical Mobility, Energy, and Social Isolation. Subsequent conservative post hoc analyses of the group means on each of these variables indicated that the group with isolated coronary artery disease differed significantly from both the hypertensives and the Normals in Physical Mobility. For the Pain subscale the subjects with isolated coronary artery disease differed significantly from those with hypertension. There were no differences among the four cardiovascular groups in perceived health problems on the subscales Emotional Reactions and Sleep. PMID- 1744913 TI - Pain sensitivity in offspring of hypertensives at rest and during baroreflex stimulation. AB - Healthy males with a parental history of hypertension (PH+) showed reduced pain sensitivity to a constrictive thigh-cuff pressure stimulus as compared to individuals without a parental history of hypertension. The protocol included eight trials in which a thigh-cuff was inflated until the subject reported the stimulus to be "painful." The PH+ group exhibited significantly lower pain sensitivity as indicated by (1) higher levels of constrictive pressure when pain was first reported and (2) lower subjective pain ratings at maximum constrictive pressure. To assess the role of baroreflex stimulation on pain sensitivity in these groups, four trials were administered concurrently with external carotid pressure stimulation. There were no significant differences in pain sensitivity in each group as a function of baroreflex stimulation. The results suggest that the hypoalgesia observed in hypertensives may predate the development of sustained elevations in blood pressure. PMID- 1744914 TI - The effects of gender on diagnosis of psychological disturbance. AB - This research examines the effect of patient gender on the detection of psychological disturbance. In Study 1, primary-care patients were requested to complete the General Health Questionnaire (GHQ), a measure of nonpsychiatric psychological disturbance, prior to their consultation. The patient's GHQ score was compared with physician judgments about the level of disturbance in that patient (N = 1913). Although there were a similar number of GHQ high scorers among males and females, the physicians classified significantly more females than males as disturbed. The doctors classified as disturbed a larger proportion of nondisturbed women than nondisturbed men. In order to explore the behavior of recent medical graduates, Study 2 examined the detection behavior of interns in an outpatient department with 384 of their patients. The interns behaved in a similar manner to the primary-care physicians. PMID- 1744915 TI - Intraosseous administration of digoxin: same-dose comparison with intravenous administration in the dog model. AB - Intraosseous access has become the method of choice for venous access in critically ill and injured children when more traditional methods are not immediately available. However, there is a paucity of information concerning drug levels achieved via the intraosseous route. We report initial data on the comparison of serum digoxin levels after administration of the drug to dogs through both the intraosseous and intravenous routes. These data indicate that intraosseous infusion of digoxin results in similar serum levels to those attained after IV administration, and may therefore afford a reliable means of initial digitalization. PMID- 1744916 TI - Current therapy of hand burn injuries. PMID- 1744917 TI - The impact of the National Cancer Act. PMID- 1744918 TI - Experts mull testing guidelines for family cancers. PMID- 1744919 TI - Cancer program becomes case study in public policy formation. PMID- 1744921 TI - Black teens have low smoking rates. PMID- 1744920 TI - Meeting spotlights advances in cancer immunotherapy. PMID- 1744922 TI - Centers improve cancer control in Appalachia. PMID- 1744923 TI - Cancer Act anniversary encourages reflection, new visions. PMID- 1744924 TI - Pharmacokinetics of leucovorin metabolites in human plasma as a function of dose administered orally and intravenously. AB - Studies have shown that conversion of leucovorin to the metabolite 5,10 methylenetetrahydrofolate (5,10-CH2FH4) is responsible for enhancement of the antitumor effects of fluorouracil given in combination with leucovorin, but the biochemical basis of this conversion in humans is not fully understood. To determine a possible sequence of metabolic steps, we studied the pharmacokinetics of leucovorin and its reduced folate metabolites in plasma in healthy volunteers. Groups of five subjects were given two equal doses of 10, 25, 125, 250, or 500 mg/m2 leucovorin, one orally and one intravenously at a 30-day interval. A sensitive radioenzymatic method that we developed previously was used to measure plasma concentrations of [S]5-formyltetrahydrofolate, 10-formyltetrahydrofolate (10-CHOFH4), 5-methyltetrahydrofolate (5-CH3FH4), and the combined 5,10-CH2FH4 plus tetrahydrofolate (FH4) pools. Intravenous administration of leucovorin resulted in dose-dependent accumulation of 5,10-CH2FH4 + FH4 exceeding 2 microM at peak levels. After oral and intravenous administration, 10-CHOFH4 and 5,10 CH2FH4 + FH4 exhibited peak levels earlier and were eliminated more rapidly than 5-CH3FH4. Accumulation of all metabolites after intravenous administration was linearly dose dependent, while oral administration appeared to result in saturation. We propose that the host activation of leucovorin suggested by these findings could be responsible for elevation of intratumor 5,10-CH2FH4 levels, thus enhancing the antitumor effects of fluorouracil. These results also suggest that 10-CHOFH4, 5,10-CH2FH4, and FH4 are intermediate metabolites and that 5 CH3FH4 is the terminal metabolite. In addition, our results indicate that attainment of high plasma levels of the metabolites active in modulation of the therapeutic effects of fluorouracil is best achieved through intravenous administration of high doses of leucovorin. Our future studies will address the proposed sequential conversion pathway and, thus, the mechanism by which pharmacologically relevant reduced folates accumulate in plasma after leucovorin administration. PMID- 1744925 TI - Human IgM monoclonal antibody 16.88: pharmacokinetics and immunogenicity in colorectal cancer patients. AB - Twenty colorectal cancer patients were given an intravenous injection of human IgM monoclonal antibody (MAb) 16.88 (8 mg) conjugated to 131I for tumor localization. After a 2-week interval, a second injection with 200, 500, or 1000 mg of unlabeled antibody added was given to groups of five patients each. at the end of the 2-hour infusion, 66% of the radioactivity remained in the circulation. Blood clearance of the 131I-labeled MAb 16.88 was biphasic with a mean half-life (T1/2 alpha) of 12 hours and T1/2 beta of 45 hours. Clearance rate was 0.09 L/hour. More than 90% of the 131I in serum was protein bound, with an immunoreactive fraction of 80% in the first 48 hours. Size exclusion chromatography indicated no degradation products other than 131I in serum and urine. The urinary excretion rate of 131I increased to 1.5% of the dose per hour at 24 hours, with 50% of the dose excreted in 34 hours. The pharmacokinetic profile of 131I-labeled MAb 16.88 was neither influenced by the total protein dose of antibody administered nor affected by specific uptake in tumor tissue in individual patients, as determined on early immunoscintigrams. The larger antibody doses showed a slightly slower excretion of 131I. The assays applied to determine immunogenicity were enzyme-linked immunosorbent assay, radioimmunoassay, and the dot-blot assay. They had sensitivities ranging from 5 ng/mL to 0.5 micrograms/mL for goat or rabbit antihuman IgM. The assays did not reveal antihuman antibody responses. PMID- 1744926 TI - Association of asbestos exposure with colorectal adenomatous polyps and cancer. PMID- 1744927 TI - Smoking-attributable cancer mortality. PMID- 1744928 TI - Pulmonary toxicity of deferoxamine in children with advanced cancer. PMID- 1744929 TI - Infections of the infratemporal fossa: imaging/clinical correlations. AB - While infections of the infratemporal fossa are occasionally documented in the otolaryngologic literature, a recent computer literature search failed to identify any significant series of cases describing this potentially fatal infection. This presentation focuses attention on the joint clinical/imaging experience of 11 cases of infratemporal fossa infection, as seen at the Soroka Medical Center of the Ben Gurion University of the Negev, in Beer-Sheva, Israel, and the Mount Sinai Hospital, of the University of Toronto, in Toronto, Canada. This manuscript reviews our experience, with particular emphasis on the effective role and accuracy of CT scanning in identifying the correct anatomic and pathologic diagnosis, as well as in the planning of treatment. PMID- 1744930 TI - Pharmacodynamics and pharmacokinetics of carprofen, a non-steroidal anti inflammatory drug, in healthy cows and cows with Escherichia coli endotoxin induced mastitis. AB - The pharmacodynamics of carprofen and its pharmacokinetics in plasma and milk of healthy cows and cows with endotoxin-induced mastitis were studied after a single intravenous dose of 0.7 mg/kg body weight. Carprofen was administered to five clinically healthy cows and to the same cows 3 weeks later, 2 h after intramammary infusion of endotoxin. Mastitis developed in all endotoxin-infused quarters. The pharmacokinetic characteristics of carprofen in healthy cows were a small volume of distribution (0.09 l/kg), a relatively low systemic clearance (2.4 ml/h kg), and a long elimination half-life (30.7 h). In the mastitic cows, systemic clearance (1.4 ml/h kg) was significantly lower (P less than 0.01), and elimination half-life (43.0 h) was significantly longer (P less than 0.01) than in the normal animals. Concentrations of carprofen in milk from healthy quarters were below the limit of detection for the assay (0.022 micrograms/ml). In milk from mastitic quarters, concentrations of carprofen increased up to 0.164 micrograms/ml during the first 12 h after induction of mastitis, but were less than 0.022 micrograms/ml at 24 to 48 h. Compared with the untreated mastitic controls, carprofen treatment significantly reduced heart rate (P less than 0.01), rectal temperature (P less than 0.001), quarter swelling (P less than 0.01) and other parameters measured. Local and systemic adverse reactions to carprofen were not observed. PMID- 1744931 TI - Further studies on the antinociceptive activity and respiratory effects of buprenorphine in sheep. AB - The thermal and mechanical analgesic profile of buprenorphine at a dose rate of 1.5 micrograms/kg i.v. was investigated in five sheep. This dose produced significant analgesia for 40 min against the thermal stimulus, but no mechanical antinociception. A higher dose rate of 12 micrograms/kg also failed to produce antinociception to a mechanical stimulus. In addition, the effect of the drug (6 micrograms/kg) on respiratory gas tensions was determined and no significant changes were observed. PMID- 1744932 TI - Studies of meclofenamic acid and two metabolites in horses--pharmacokinetics and effects on exercise tolerance. AB - The pharmacokinetics and the effects on treadmill exercise of the anti inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non compartmental analysis showed a mean absorption time of 4.3 h. The pharmacokinetics of two metabolites of meclofenamic acid were also studied in two of the horses. The elimination half-lives of the two metabolites were virtually the same in each horse (3.0 h and 3.4 h). The blood lactate response to exercise was significantly decreased after treatment with meclofenamic acid, indicating a lower utilization of the glycolytic ('anaerobic') energy contribution during exercise. Circulatory capacity was apparently unaffected with an unchanged heart rate response to exercise. PMID- 1744933 TI - Clenbuterol plasma concentrations after repeated oral administration and its effects on cardio-respiratory and blood lactate responses to exercise in healthy Standardbred horses. AB - To evaluate the effects of clenbuterol on cardio-respiratory parameters and blood lactate relation to exercise tolerance, experimental horses performed standardized exercise tests on a high-speed treadmill before and after administration of the drug. Clenbuterol was administered in feed to six healthy Standardbreds at a dose rate of 0.8 micrograms/kg b.wt twice daily for 5.5 days. Each horse was tested twice, without and with a respiratory mask, during two consecutive days. One week elapsed between the baseline tests without drug and the tests with clenbuterol treatment (each horse served as its own control). The results show an unchanged heart rate response to exercise 2 h after the last clenbuterol administration. The blood lactate response and the arterial oxygen tension during exercise did not differ before and after drug treatment. The oxygen uptake as well as pulmonary ventilation relative to the work load performed was essentially unaffected. The arterial pH during exercise was significantly increased (P less than 0.05) following clenbuterol treatment. Plasma levels of clenbuterol were maximal 2 h post-administration with values between 0.45 and 0.75 ng/ml. The plasma half-life of elimination was 10.4 h (+/- 2.25 SD). In conclusion, clenbuterol did not cause any major effects on the cardio-respiratory and blood lactate parameters studied in healthy horses performing submaximal exercise tolerance tests. PMID- 1744934 TI - Pharmacokinetics of tinidazole in dogs and cats. AB - Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study. Tinidazole was completely absorbed at both oral dose levels in cats and dogs. Peak tinidazole concentration in plasma was 17.8 micrograms/ml in dogs and 22.5 micrograms/ml in cats after 15 mg/kg p.o. The oral dose of 30 mg/kg resulted in peak levels of 37.9 micrograms/ml in dogs and 33.6 micrograms/ml in cats. The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half-life that was twice as long in cats (8.4 h) as in dogs (4.4 h). The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats. Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole-sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg. From the pharmacokinetic standpoint tinidazole seems to be well-suited to clinical use in small animal practice. PMID- 1744935 TI - Comparison of mucosal drug conjugative rates along the gastrointestinal tract of female sheep. AB - The comparative distribution of p-nitrophenol UDP-glucuronosyl-transferase, 1 chloro-2,4-dinitrobenzene glutathione-S-transferase and sulphamethazine N acetyltransferase activities was studied along the gastrointestinal mucosa of female Lacaune sheep. Gastrointestinal mucosa was characterized by a very low and unequal N-acetyltransferase activity when activities were expressed per g of wet organ. The duodenum contained highest activities (4.1 nmol/g min). When results were expressed per mg of cytosolic protein, the duodenal activity (0.64 nmol/mg min) was sixfold higher than in liver (0.11 nmol/mg min). There was a lack in N acetyltransferase activity accepting isoniazid as substrate. Glucuronosyltransferase activity was approximately threefold higher in microsomal fractions of the mucosal lining of gastric and colonic intestine (0.43-0.58 nmol/g min) than in small intestine or caecum (0.10-0.26 nmol/mg min). Concerning cytosolic glutathione S-transferase activity, two- to threefold higher activities were obtained in omasum, jejunum, duodenum and ileum (1021-2164 nmol/g min) than in other parts (341-799 nmol/g min) when results were expressed per g of wet organ. These data were compared with corresponding hepatic activities determined in the same six female sheep. PMID- 1744936 TI - Pharmacokinetics of antipyrine and sulphadimidine (sulfamethazine) in camels, sheep and goats. AB - The pharmacokinetics of antipyrine and sulphadimidine were studied in male camels, sheep and goats. The two drugs were administered concomitantly. Following intravenous injection of antipyrine (25 mg/kg) and sulphadimidine (sulfamethazine) (100 mg/kg), the pharmacokinetics of the two drugs were adequately described by a one-compartment model. Antipyrine half-life in goats (2.58 h) was shorter than that in sheep (4.04 h) and camels (18.78 h). The plasma clearance was greatest in goats then sheep and then camels. For sulphadimidine, a significantly greater volume of distribution was observed in camels and the greatest plasma clearance and shortest half-life were reported in goats. Sulphadimidine half-life was 2.77 h in goats, 4.72 h in sheep and 7.36 h in camels. The present results suggest that goats have the fastest elimination of these drugs from the circulation, followed by sheep and then camels. PMID- 1744937 TI - The effects of experimentally induced bronchopneumonia on the pharmacokinetics and tissue depletion of gentamicin in healthy and pneumonic calves. AB - The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90-140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P less than 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central fluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue-depletion models using multiple regression improved the prediction of a concentration in a given tissue. PMID- 1744938 TI - Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia. AB - Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaCO2 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91-120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent. PMID- 1744939 TI - Relaxant effects of theophylline and clenbuterol on tracheal smooth muscle from horse and rat in vitro. AB - A comparison between the relaxant effects of clenbuterol and theophylline on horse tracheal smooth muscle has been made in vitro. Rat tracheal smooth muscle was also investigated as a reference. The tracheal preparations were initially contracted with carbachol since the smooth muscle did not spontaneously develop tone. The response of the carbachol-contracted preparations to theophylline was the same in the two species. The response to clenbuterol varied. In only five out of eleven horses were the tracheal smooth muscles sensitive to clenbuterol (mean pD2 = 7.92 M). In the remaining six horses the tracheal smooth muscles were insensitive to clenbuterol (mean pD2 = 3.59 M), yet the preparations responded well to theophylline with complete relaxation. All rat tracheal preparations were insensitive to clenbuterol. PMID- 1744940 TI - The pharmacokinetics and locomotor activity of alfentanil in the horse. AB - The pharmacokinetics of alfentanil were investigated in the horse. Four doses of alfentanil (4, 10, 20 and 40 micrograms/kg) were given to four horses at different times and their locomotor activity monitored. Doses of 20 and 40 micrograms/kg produced a significant increase in locomotor activity. The plasma concentrations of alfentanil were measured in six standing horses and the pharmacokinetics calculated. It was found that the decay curves were best described by a biexponential equation. The elimination half-life (t1/2 beta) was 21.65 +/- 3.99 min and the clearance (Cl) was 14.1 +/- 0.7 ml/kg/min. The same horses were anaesthetized with xylazine-ketamine and maintained with halothane in oxygen for the first experiment and isoflurane in oxygen for the second experiment. The pharmacokinetics were again calculated from measured plasma alfentanil concentrations. There were significant differences between the kinetics in the conscious and the anaesthetized animals but there were no significant differences in alfentanil kinetics between the two anaesthetic agents. The t1/2 beta for alfentanil under halothane and isoflurane anaesthesia were 55.95 +/- 20.77 and 68.03 +/- 23.22 min, respectively, and the Cl values were 14 +/- 1.7 and 13.6 +/- 1.32 ml/kg/min. PMID- 1744941 TI - Plasma thiamphenicol concentrations in calves after intratracheal administration. PMID- 1744942 TI - Concentrations of phenylbutazone and oxyphenbutazone in post-parturient mares and their neonatal foals. PMID- 1744943 TI - Disposition kinetics of gentamicin in buffalo calves (Bubalus bubalis) following single intravenous administration. PMID- 1744944 TI - Effect of some organic vehicles on the rate of elimination of intravenously administered ronidazole in pigeons. PMID- 1744945 TI - Haemophilus influenzae declining among young? PMID- 1744946 TI - North Carolina's maternal health campaign ignores smoking, maternal health advocates fume. PMID- 1744947 TI - Implanted defibrillators slash sudden death rate in study, thousands more may get them in future. PMID- 1744948 TI - From the Health Care Financing Administration. PMID- 1744949 TI - From the Centers for Disease Control. Foodborne nosocomial outbreak of Salmonella. PMID- 1744950 TI - From the Centers for Disease Control. Patterns of sexual behavior change. PMID- 1744951 TI - A piece of my mind. Requiem for an unknown leper. PMID- 1744952 TI - Use of animals in medical education. PMID- 1744954 TI - Conflicts in health care spending. PMID- 1744953 TI - Reimbursement, beneficence, and advance directives. PMID- 1744955 TI - Differences in mortality from coronary artery bypass graft surgery. PMID- 1744956 TI - Hospital variables associated with quality of care for breast cancer patients. AB - OBJECTIVE: To determine the degree of compliance with clinical standards among hospitals for care of breast cancer patients and account for variations in compliance. DESIGN: Analysis of cancer registry data submitted to the American Cancer Society, Illinois Division, Chicago, for a concurrent prospective descriptive study of breast cancer, supplemented by other hospital data from public sources. SETTING: Ninety-nine Illinois hospitals evenly distributed among rural counties, counties with small cities outside the Chicago metropolitan area, exurban counties in the Chicago metropolitan area, suburban Cook County, and urban Chicago. PATIENTS: A total of 5766 newly diagnosed patients with histologically confirmed breast cancer in 1988, representing 84% of the estimated 6900 new cases in the state for that year. MAIN OUTCOME MEASURES: Descriptive statistics and multiple linear regression analyses of five dependent quality variables from clinical indicators related to early diagnosis, hormone receptor determination, adjuvant therapy, radiation therapy, and axillary lymph node dissection. RESULTS: At the hospitals studied, (1) late stage (IIb through IV) at diagnosis was associated with urban location, higher proportion of poorly insured patients, fewer breast cancer cases treated, and lower oncology charges (proportion of variance explained, R2 = .50, P less than .00001); (2) omission of hormone receptor test for stages II through IV was associated with urban location and higher proportion of poorly insured patients (R2 = .18, P less than .00003); and (3) omission of indicated radiation therapy was associated with urban location and fewer breast cancer cases (R2 = .21, P less than .00001). Omission of adjuvant therapy and omission of axillary lymph node dissection were not significantly associated with any of the hospital variables examined. CONCLUSIONS: The findings suggest that there is a group of urban hospitals, generally small and marginally reimbursed, where comprehensive diagnosis and treatment of breast cancer are not obtained. PMID- 1744957 TI - Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies. AB - OBJECTIVES: To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection. DESIGN: Coded serum samples prospectively collected from children born to HIV infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. SETTING: A university hospital in Baltimore, Md, and an outpatient clinic in Port au-Prince, Haiti. POPULATION: Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. OUTCOME MEASURES: Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older. RESULTS: The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively. CONCLUSION: Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries. PMID- 1744958 TI - Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection. AB - OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%- no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms. PMID- 1744959 TI - 25-year mortality after surgical repair of congenital heart defect in childhood. A population-based cohort study. AB - OBJECTIVE: To determine long-term survival and the cause of death after repair of one of eight congenital heart defects in childhood. DESIGN: Cohort study. SETTING: General community. PARTICIPANTS: All Oregon residents with one of eight congenital heart defects, which was repaired surgically between 1958 and 1989 when the patient was aged 18 years or younger, including (1) tetralogy of Fallot; (2) isolated ventricular septal defect; (3) isolated atrial septal defect; (4) coarctation of the aorta; (5) aortic valvular stenosis; (6) pulmonary valvular stenosis; (7) transposition of the great arteries; and (8) patent ductus arteriosus. Follow-up of this cohort of 2701 individuals was obtained from 94%. MAIN OUTCOME MEASURE: Mortality from cardiac and noncardiac causes. RESULTS: Age at surgery and operative mortality have decreased significantly over the last 30 years. Late cardiac mortality at 25 years after surgery was 5% for tetralogy of Fallot and isolated ventricular septal defect, 10% for coarctation of the aorta, 17% for aortic stenosis, 5% for pulmonic stenosis, and less than 1% for patent ductus arteriosus; there were no late cardiac deaths after atrial septal defect repair. For transposition, late cardiac mortality was 15% at 15 years after the Mustard operation and was 2% at 10 years after the Senning operation. CONCLUSION: Surgical repair of most congenital heart defects is associated with lingering cardiac mortality, particularly for aortic stenosis, coarctation, and transposition. PMID- 1744960 TI - A critical analysis of the resource-based relative value scale. AB - BACKGROUND--There is a general perception that procedural medical services are reimbursed at an inappropriately greater rate than cognitive services. By congressional mandate, the Health Care Financing Administration (HCFA) has been directed to establish a Medicare fee schedule to shift funding under a budget neutral assumption from procedural to cognitive services. To provide a rational basis for this change, Hsiao et al (Harvard-Hsiao) developed a resource-based relative value scale (RBRVS) that equates the value of a service to the resources necessary to generate the service. METHODS--Instead of focusing on relative values and fee schedules ("price-per-unit-service"), the present study employs the standard commercial/industrial method of determining reimbursement rate (income divided by hours of labor) for 15 medical and surgical specialties. Data from independent sources are used to determine income and hours of professional effort for each of the specialties studied. Harvard-Hsiao and HCFA predicted the percent change in income for each of the specialties under the initial RBRVS and the HCFA fee schedule. The predicted income was then employed in this study to recompute reimbursement rates under the newly proposed payment systems. RESULTS: CURRENT PAYMENT SYSTEM--Average annual incomes for medical and surgical specialties are $124,500 and $176,600, respectively, a 42% difference (P = .03). Average weekly work hours (nominal hours, as adjusted for overtime) for medical and surgical specialties are 70.6 and 87.8, respectively (P = .005). Average hourly reimbursement rates for medical ($33.90) and surgical ($38.80) specialties are not substantially different (P, not significant). The difference in annual income is explained by the 17.2 hours per week of additional work hours by surgeons. The erroneous perception that procedurists are reimbursed at a higher rate than cognitive practitioners likely arises from differences in billing methods by which surgeons shift charges for cognitive work hours to the 18% of their time spent in the operating room. RESULTS: PROPOSED RBRVS AND HCFA PAYMENT SYSTEM--The income of all specialties is equalized about a mean of $132,500 (+/- $21,400 [1 SD]) by varying reimbursement rates in such a way that the effect of working hours is fully discounted. Reimbursement rates under the proposed payment system make no recognition of the hours of professional effort, postgraduate specialty training, or putative differences in the nature of the physician's work. CONCLUSION: --The RBRVS, and the HCFA fee schedule to the extent that it is based on that scale, are inappropriate bases for the reform of the physician reimbursement system. PMID- 1744961 TI - 'Melanoma? It can't be melanoma!' A subset of melanomas that defies clinical recognition. AB - We diagnosed histologically 178 cases of malignant melanoma in 1990. Thirteen cases were recorded in which the diagnosis of malignant melanoma was not considered by the clinician prior to biopsy or, in retrospect, following pathologic diagnosis. Eight of the 13 lesions were amelanotic. The majority were deeply invasive at the time of biopsy, implying poor prognosis. Despite improvements in early detection of malignant melanoma, a significant subcategory of melanomas escapes clinical diagnosis. PMID- 1744962 TI - Cost-effectiveness of HA-1A monoclonal antibody for gram-negative sepsis. Economic assessment of a new therapeutic agent. AB - OBJECTIVE: To assess the cost-effectiveness of the HA-1A monoclonal antibody for the treatment of gram-negative bacteremia. DESIGN: Cost-effectiveness analysis of a randomized, double-blind, placebo-controlled trial using clinical efficacy data reported in the medical literature. SETTING: Hospitalized patients with sepsis. PATIENTS: 543 patients with sepsis and suspected gram-negative infection. Patients enrolled in the study met strict criteria for sepsis, including fever or hypothermia (less than 35.6 degrees C or greater than 38.3 degrees C), tachycardia (greater than 90 beats per minute), tachypnea (greater than 20 breaths per minute), and hypotension or two of six signs of systemic toxicity. INTERVENTION: HA-1A vs placebo in addition to usual care. MAIN OUTCOME MEASURES: We determined the range of possible cost-effectiveness ratios for HA-1A therapy, using modeling techniques when clinical or economic variables were unknown. We subjected the model to rigorous sensitivity analysis. We calculated the incremental cost of care and years of life saved for patients with sepsis and modeled two different treatment strategies: treat all patients with sepsis or test and then treat only patients with positive test results. $24,100 per year of life saved based on the treat strategy and $14,900 based on the test strategy. In sensitivity analysis the ratios ranged from $5200 to $110,200 per year of life gained. Annual costs of care for these two strategies are $1.3 billion for the test strategy and $2.3 billion for the treat strategy. CONCLUSION: Economic assessment of new technologies early in their development can be used to guide their efficient clinical introduction. PMID- 1744963 TI - Quality of care. Time to act. PMID- 1744964 TI - Advances in early diagnosis of perinatal HIV infection. PMID- 1744965 TI - Blood, money, and hemophiliacs--the fatal story of France's 'AIDSgate'. PMID- 1744966 TI - Diarrhoea. PMID- 1744967 TI - Etiology and management of diarrhoeal diseases in Karachi. AB - The incidence of diarrhoeal disease are very high in our population and bacterial etiology amounts to 43.55% of all cases. Pathogen such as Aeromonas hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica and Campylobacter are also present in significant numbers, they make up 50% of bacterial causes. All enteric pathogens can be easily isolated on commonly used media and could be precisely identified by simple biochemical tests. PMID- 1744968 TI - Ramadan fasting and thyroid hormone profile. AB - A study comprising 41 males, 5 females of the age ranging from 28 to 56 years was conducted during Ramadan of 1989 to compare T3, T4 and TSH levels in fasting with the levels of non-fasting conditions. Each individual gave 6 blood samples: One sample was taken 20 days before the onset of Ramadan, 3 samples at different fasting days and last two samples were drawn 23 days and five months after the end of Ramadan, respectively. The results showed a significant gradual rise in TSH throughout the fasting month, although the mean levels remained within normal limits. Pre- Ramadan levels were re-attained well after the end of Ramadan. There was no significant change in T3 and T4 levels. PMID- 1744969 TI - Sero-epidemiological survey of malaria by immunofluorescence in Pakistan (District Gujranwala-Punjab). AB - Indirect Immunofluorescence Antibody (IFA) Technique was employed, for field detection of malarial parasite. The technique involved application of homologous antigen slides of Plasmodium falciparum and P. vivax prepared in the field conditions. Serological study, simultaneously using P. falciparum and P. vivax antigens, brought out a clearer picture of distribution and role of the parasite species in the epidemiology of the disease in the area studied. The survey supported the contention of persistence of transmission of malaria in Gujranwala District. PMID- 1744970 TI - Sertoli cell only syndrome (SECOS): lessons from case studies. AB - Between June 85 and December 87, 69 testicular biopsies were submitted for histopathological examination during investigation of infertility; ten (14%) patients had a Sertoli cell only syndrome. The history, clinical features, and hormonal profiles were analyzed in an attempt to categorize these patients on aetiological basis. Two followed treatment of malignancy--one by radiation for testicular cancer and one by cyclophosphamide for a lymphoma. One had unilateral cryptorchidism. Mumps was etiological factor in one patient. FSH levels determined in 6 patients were elevated in all suggesting a possible dependence of (sick) Sertoli cells on spermatogenic cells for production of inhibin. Alternative explanations include changes in sertoli cell enzymes or FSH receptors. Testosterone levels are in the low normal range suggesting that Leydig cells may also be affected by the etiological factor producing the syndrome. Two patients who had earlier received a higher Johansen score were found to have a sertoli cell only syndrome on expert review of testicular biopsies. It is suggested that the condition is more common than hitherto reported and is often confused with maturation arrest. Testicular histopathology should be done by specialists in testicular pathology. PMID- 1744971 TI - Maternal morbidity in the Department of Obstetric and Gynaecology, Jinnah Postgraduate Medical Centre Karachi. AB - Maternal morbidity was observed in 377 obstetric cases at Jinnah Postgraduate Medical Centre (JPMC) during a period of one year. Morbidity rate was 4.4% of total deliveries. Three hundred and twenty-four (86%) mothers had no proper antenatal supervision. Infection was more common after abdominal delivery and injury to genital tract after vaginal delivery. The most serious injury was rupture of gravid uterus. Thirty-seven cases of ruptured uterus were admitted in one year and 5 cases occurred within the hospital (1 in 1225 deliveries). PMID- 1744972 TI - Neuro osteoarthropathy (Charcot's joint) in a young diabetic. PMID- 1744973 TI - Collagenous colitis. PMID- 1744974 TI - Clinical trials in surgery. PMID- 1744975 TI - The role of vascular smooth-muscle cells in atherogenesis: phenotypic modulation of the medial smooth-muscle cells in the aortic bifurcation. AB - To elucidate the mechanism of migration of vascular smooth-muscle cells (SMCs) from media to intima, we have investigated the phenotypic modulation of the medial SMC at bifurcation of the celiac artery in 5 children and 3 young persons using a transmission electron microscope. We counted the number of separated SMCs from the elastic layers, although the medial SMCs are fundamentally attached to the elastic fibers, and are still contractile in their phenotypes. Both proximal and distal portions revealed that SMCs in the media were more or less present in the separated state and were ultrastructurally consistent with the synthetic state of SMC in the proximal area and the contractile state in distal areas. In order to migrate from media to intima, medial SMC should separate from the elastic layers and transform their phenotypes. In this paper, we examined the relationship between vascular SMCs and elastic layers in the media and ascertain that it was responsible for the contribution to the subsequent phenotypic modulation and their migration of medial SMCs. PMID- 1744976 TI - Impairment of a protective system against atherosclerosis--genetic disorders in HDL metabolism. PMID- 1744977 TI - Anticoagulant heparin-like glycosaminoglycans on endothelial cell surface. AB - Atherosclerosis is associated with an accumulation of proteoglycans. Proteoglycans and/or glycosaminoglycans, in particular heparan sulfate, produced by endothelial cells are thought to play important roles in diverse vascular functions. Of particular note is that they possess anticoagulant functions, i.e., heparin-like antithrombin cofactor activity. Incubation of antithrombin III with endothelial cell cultures resulted in a specific, saturable binding of this protease inhibitor presumably to the endothelial cell surface. In addition, thrombin inactivation by antithrombin III was accelerated on the endothelial surface, providing strong evidence that heparan sulfate on the surface of endothelial cells exerts a heparin-like activity. beta-D-xyloside or cytokine treatments altered the synthesis of heparan sulfate on the endothelial cell surface, resulting in decreased anti-thrombin III binding and diminished heparin like anticoagulant activity of endothelial cells. The modulation of endothelial heparin-like compounds by these pharmacologic or physiologic agents may have pathophysiologic implications in thrombosis as well as atherogenesis. PMID- 1744978 TI - Platelet-derived endothelial cell growth factor: structure and function. AB - Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa single chain polypeptide, which stimulates the growth and chemotaxis of endothelial cells in vitro and angiogenesis in vivo. Purification from human platelets and cDNA cloning of PD-ECGF disclosed that it is a novel type of angiogenic factor without sequence similarity to hitherto known proteins. PD-ECGF is present in human platelets as well as in placenta. Amino acid sequencing of PD-ECGF from human placenta revealed that the placental form has an additional 5 amino acids at the N-terminus. In cultured cells, it is produced by normal fibroblasts as well as some transformed cell lines. PD-ECGF lacks a hydrophobic signal sequence and remains inside the producer cells. PD-ECGF may act at sites of injury as a wound hormone and thus play an important role under several physiological and pathological conditions. PMID- 1744979 TI - Small GTP-binding proteins in bovine aortic smooth muscle. AB - In bovine aortic smooth muscle, GTP-binding activity was equally distributed in the membrane and cytosol fractions. The most abundant GTP-binding proteins (G proteins) in each fraction were purified to near homogeneity and characterized. The most abundant G protein in the membrane fraction had a Mr value of about 22,000 (m22K G) as estimated on sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE). m22K G and the human platelet smg p21, a ras p21 like G protein having the same effector domain as ras p21s, were eluted at the same retention time on C4 reversed-phase high performance liquid chromatography (HPLC). Moreover, m22K G was specifically recognized by an anti-smg p21 polyclonal antibody. m22K G was phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein. The most abundant G protein in the cytosol fraction had a Mr value of about 21,000 (c21K G) as estimated on SDS-PAGE. c21K G was ADP-ribosylated by botulinum ADP ribosyltransferase and about 0.4 mol of ADP-ribose was maximally incorporated into 1 mol of c21K G. c21K G and the bovine brain rhoA p21, another ras p21 like G protein, were eluted at the same retention time on C4 reversed-phase HPLC and migrated at the same position on two-dimensional gel electrophoresis. These results indicate that the major G proteins in the membrane and cytosol fractions of bovine aortic smooth muscle are smg p21 and rhoA p21, respectively. Possible roles of these G proteins in vascular smooth muscle are discussed. PMID- 1744980 TI - Decreased sulfhydryl groups of serum albumin in coronary artery disease. AB - We hypothesized that oxidative processes in myocardial tissues initiated by ischemia also cause the same kind of changes in blood proteins and lead to oxidation of sulfhydryl groups (SH). To test this hypothesis, the ratio (%MA) of mercaptalbumin to total albumin (= mercaptalbumin + nonmercaptalbumin) and the total SH contents of serum were measured in patients with coronary artery disease. There was a positive correlation between %MA and total SH contents and both values were reduced in proportion to the severity of the coronary artery disease. Furthermore, these values were lower early hours after the onset of acute myocardial infraction than 4 weeks later. These results support our hypothesis, and may provide a basis for the administration of agents which can counteract oxidative stress in order to protect myocardium in patients with coronary artery disease. PMID- 1744981 TI - A case of unusual longevity of tetralogy of Fallot confirmed by cardiac catheterization. AB - We describe a 61-year-old woman with tetralogy of Fallot and dextrocardia with complete situs inversus. The functional status of this patient was New York Heart Association (NYHA) class II and the systemic blood pressure was 100/54 mmHg. The hematocrit was 54.4% and the arterial partial pressure of oxygen was 53 mmHg. On cardiac catheterization, both pulmonary valvular and infundibular stenoses were of equal severity and the aorta and main pulmonary artery were of equal size. We think that this patient has survived to this unusual age for tetralogy of Fallot because of unusually low systemic pressure and a proper balance between the ventricular septal defect and the pulmonary stenosis. PMID- 1744982 TI - A case of clinically diagnosed pure septal infarction. AB - Interventricular septal involvement in myocardial infarction is usually associated with infarction of the left ventricular anterior free wall, as the obstruction is at the major portion of the left anterior descending coronary artery. Acute myocardial infarction with obstruction only of the first septal branch is rare. We describe here a case of pure septal infarction. The case was diagnosed by emergency coronary arteriogram (CAG). Although the patient had a large first septal branch, his global left ventricular function was preserved. Abnormal findings were localized in only septal region as determined by left ventriculography (LVG), two-dimensional echocardiography (2DE), and 99mtechnetium pyrophosphate (99m Tc-PYP) and 201thallium (201Tl) myocardial scintigraphy. PMID- 1744983 TI - The importance of good endocardial reflow immediately after reperfusion for myocardial salvage in dogs. AB - We studied the importance of reflow after reperfusion for myocardial salvage. In 19 open-chest dogs, the left anterior descending coronary artery was occluded for 3h and then reperfused. Non-radioactive colored microspheres were injected into the left atrium to measure regional myocardial blood flow (RMBF). Immediately after occlusion, RMBF was reduced to 23 +/- 2% (of control) in the inner layer and 32 +/- 2% in the outer layer. Five minutes after reperfusion, RMBF was increased to 170 +/- 20% and 156 +/- 11% of control in the inner and outer layers, respectively. One week later, RMBF in the inner layer was reduced to 63 +/- 4% but it was not reduced (100 +/- 6%) in the outer layer. There was a roughly positive correlation between the inner/outer flow ratio measured 5 min after reperfusion and myocardial creatine kinase activity. Myocardial necrosis determined by triphenyl tetrazolium chloride stain varied inversely with the inner/outer flow ratio. These results indicate that good reflow in the inner layer 5 min after reperfusion is a favorable indicator for myocardial salvage. PMID- 1744984 TI - Blood coagulation and fibrinolysis in SART-stressed (repeated cold-stressed) rats and drug effects on the altered hemostatic parameters. AB - Blood coagulation and fibrinolytic activity was studied in SART (specific alternation of rhythm in temperature)-stressed animals found to exhibit thrombocytopenia and prolonged bleeding time, and drug effects on the abnormalities were evaluated. 1) SART-stressed rats revealed prolongation of activated partial thromboplastin and thrombin time, no change in prothrombin time, decreased plasma fibrinogen levels, and shortened euglobulin clot lysis time (ELT). Antithrombin III and alpha 2-plasmin inhibitor activity remained constant following stress exposure. 2) During stress, fibrinogen levels declined from day 5 and remained depressed up to day 14. Reduction in ELT developed in a similar manner to fibrinogen. 3) Decreased fibrinogen levels were prevented by consecutive doses of tranexamic acid, an antifibrinolytic, and Neurotropin, a sedative analgesic. Shortened ELT was counteracted by chronic treatment with Neurotropin and alprazolam, an anxiolytic. Single administrations of the above agents failed to affect either change. These results indicate that SART-stressed animals exhibit suppressed intrinsic coagulability and enhanced fibrinolytic activity, but normal extrinsic coagulability. Considering the previous report together with the above results, the hemostatic system under SART stress tends uniformly toward hemorrhage. Moreover, Neurotropin appears to improve and normalize hemostatic imbalance due to SART stress, a chronic form of stress. PMID- 1744985 TI - Effect of phospholipase A2 on temperature-induced high-affinity [3H]tryptamine binding sites in rat brain. AB - To investigate a link between membrane phospholipids and tryptamine binding molecules, we examined the effects of phospholipases A2 and D on the temperature sensitive high-affinity [3H]tryptamine binding sites in rat brain. When the phospholipase A2-treated membranes were exposed to 1% bovine serum albumin (BSA) before assaying for [3H]tryptamine binding, a complete dose-dependent inhibition curve was observed. At a concentration of 0.03 U, the action of phospholipase A2 resulted in the splitting of phosphatidylserine (PS), choline phosphatides (PC) and ethanolamine phosphatides (PE) by about 32, 34 and 65%, respectively, and reduced [3H]ligand binding by about 32%. On the contrary, in the case of phospholipase D (500 U), PS and PC decreased by about 8% and 33% and PE by about 29% with no significant alteration in the binding capacity. Moreover, Scatchard analysis of the [3H]tryptamine binding showed that phospholipase A2 drastically increased only the KD value of the high affinity sites, and this was accompanied by a decrement of the Bmax values of both the high and low affinity binding sites. From these results, it is inferred that certain lipids (PS) may be a modulator for the function of the temperature-induced high-affinity [3H]tryptamine binding molecules. PMID- 1744986 TI - Congestive heart failure model in rabbits: effects of digoxin and a drug containing toad venom. AB - A low-output-type heart failure model was established in rabbits by protease treatment of the surface of the left ventricular anterior wall. Heart rate, aortic blood flow (AoF), left ventricular pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and mean blood pressure (MBP) remained at a normal level. Intraduodenal administration of digoxin and a drug containing toad venom (Kyushin:KY) improved the hemodynamic parameters by increasing the AoF, LVP and max dP/dt and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of digoxin and KY on this heart failure model originate from their cardiotonic activity. PMID- 1744987 TI - Enhancement of the ambulation-increasing effect of opioid analgesics by ethanol in mice. AB - The interaction between opioid analgesics (morphine and buprenorphine) and central depressants (ethanol, pentobarbital and diazepam) was investigated by means of ambulatory activity in mice. The ambulation-increasing effect of both morphine (10 mg/kg, s.c.) and buprenorphine (1 mg/kg, s.c.) was enhanced by the combined administration of ethanol (0.8-3.2 g/kg, p.o.) in a dose-dependent manner. Naloxone (0.1 mg/kg, s.c.) was effective for reducing the enhanced ambulatory activity. The pretreatment with Ca-cyanamide (5 mg/kg, p.o., 30 min before) reduced the enhancement of the ambulation-increasing effect induced by the combined administration of opioid analgesics with ethanol, although it scarcely modified that of morphine and buprenorphine alone. On the other hand, neither pentobarbital (1-30 mg/kg, s.c.) nor diazepam (0.25-2 mg/kg, s.c.) modified markedly the ambulation-increasing effect of morphine and buprenorphine. The present results suggest that ethanol specifically interacted with opioid analgesics when the mouse's ambulatory activity was used as the indicator. PMID- 1744988 TI - Studies on antinephritic effect of TJ-8014, syo-saiko-to-kyo-shyokyo-ka-ouren bukuryou (5): Effects on puromycin aminonucleoside nephrosis and its mechanisms. AB - The effect of TJ-8014, a lyophilized extract of Syo-Saiko-To without Zingiberis rhizoma, annexing Coptidis rhizoma and Hoelen, on puromycin aminonucleoside (PAN) nephrosis in comparison with the effect of dipyridamole was evaluated. PAN nephrosis was induced in rats by intraperitoneal injections of PAN, once daily for 6 days. When TJ-8014 was given from the initial day of PAN treatment (just before PAN injection) at 2.0 g and 4.0 g/kg/day, p.o., it was markedly inhibited urinary protein excretion and elevation of serum cholesterol content-throughout the experimental periods. In addition, the mild adhesion of Bowman's capsule to capillary walls in glomeruli was also improved by TJ-8014 at 2.0 g and 4.0 g/kg/day, p.o. Dipyridamole was also effective in inhibiting the urinary protein excretion as well as histopathological changes. TJ-8014 at 4.0 g/kg/day, p.o. inhibited the decrease in superoxide dismutase (SOD-like), catalase and glutathione peroxidase activities in the renal cortex and SOD-like activity in the glomeruli in PAN-induced nephrosis. Dipyridamole failed to inhibit the decrease in scavenger activities. These results suggest that TJ-8014 is effective against PAN-induced nephrosis, and they suggest that the mechanisms of action of this medicine may be partly due to the enhancing activities of scavengers in the renal cortex and glomeruli. PMID- 1744989 TI - A reliable method for the production of antral gastric ulcer by a combination of 2-deoxy-D-glucose, aspirin and ammonia in rats. AB - In order to establish a reliable method for the production of gastric antral ulcer in rats, combined treatments with three factors: a vagal stimulant, a mucosal barrier breaker and a necrotizing agent were investigated. By the combined administration of 2-deoxy-D-glucose (2-DG; 200 mg/kg, i.v.), aspirin (100-400 mg/kg, p.o.) and hydrochloric acid (0.15 and 0.35 N, 0.5-1.5 ml/100 g, p.o.) or ammonia solution (0.5-1.0%, 0.5-1.5 ml/100 g, p.o.), gastric lesions were prominently induced in sites of both the corpus and antrum on day 2. The largest antral ulcer was induced by the combination of 2-DG (200 mg/kg), aspirin (200 mg/kg) and ammonia solution (1%, 10 ml/kg); and the mean antral ulcer index (mm2) was 43.1 +/- 4.4 and the incidence was 100%. The antral ulcer was found to penetrate the muscularis mucosae and still observed on day 21 and day 28 after ulcer induction in a few cases. From these findings, it was indicated that this antral ulcer would be a useful model for studying the etiology and therapy of gastric ulcer disease. PMID- 1744990 TI - Drug effects on cognitive function in mice determined by the non-matching to sample task using a 4-arm maze. AB - A new task for the analysis of drug effects on the cognitive function in mice was investigated using a 4-arm maze with three selectable arms. Each trial consisted of a forced run either to the right or left arm containing a food pellet, which was changed for each trial, followed by a free-choice run after a delay (0-120 sec). The correct response was to turn to the arm 180 degrees opposite from the forced one. Entrance into the center arm in the free-choice run, which was called the non-reward response, was not reinforced at any time. As the delay became longer, correct responses decreased, but non-reward response errors remained unchanged in the well-trained mice. Without increasing the non-reward response, scopolamine and atropine, but not methylscopolamine, decreased the correct response in a delay-dependent manner at a low dose range, while diazepam did so in a delay-independent manner. Physostigmine ameliorated scopolamine-induced impairment in performance, but had less effect on the delay-induced decrease in the correct response. Other tested drugs (chlorpromazine, haloperidol, apomorphine, phentolamine, propranolol, lithium chloride, ketamine, and caffeine) had no significant effect on performance. These results suggest that CNS muscarinic blockades and diazepam treatment selectively attenuate working memory in different ways. PMID- 1744991 TI - Effects of MCI-727, a new anti-ulcer agent, on plasma secretin concentration in rats and dogs and pancreatic exocrine secretion in rats. AB - In the present study, we investigated the effects of MCI-727, a new anti-ulcer agent, on plasma immunoreactive secretin concentration in rats and dogs using secretin specific RIA with the ethanol extraction method. Plasma secretin levels were increased dose-dependently 10 min after oral administration of MCI-727 in rats (control: 5.5 +/- 0.6; MCI-727, 10 mg/kg: 10.4 +/- 2.6; 30 mg/kg: 15.3 +/- 1.5; 100 mg/kg: 20.7 +/- 2.6 pg/ml, n = 6). Teprenone also caused a significant increase of plasma secretin at 10 min after oral administration at the doses of 30, 100 and 300 mg/kg. Under the same conditions, MCI-727 and teprenone did not alter the plasma immunoreactive gastrin concentration in rats. From the results of the time course study, the increasing effect of MCI-727 (30 mg/kg, p.o.) on plasma secretin remained for at least 240 min after administration. On the other hand, the increasing effect of teprenone (200 mg/kg, p.o.) was only observed at 30 and 60 min after administration. Furthermore, MCI-727 had increasing effects on plasma secretin concentration in dogs, but teprenone had no effects in this species. The volume of pancreatic secretion and the pancreatic bicarbonate output increased after intra-duodenal administration of MCI-727 at 30 and 100 mg/kg in rats. Similar effects were also observed with teprenone (30-300 mg/kg, i.d.) or secretin (Secrepan, 0.1-1.0 unit/kg, i.v.). PMID- 1744992 TI - Possible optimization of sulphadimidine dosage for acetylator phenotyping. AB - The effect of different doses of sulphadimidine (250, 500, 750 and 1000 mg) on acetylation capacity in 10 normal individuals was investigated in a randomized cross-over study design. The subjects were initially phenotyped with an oral dose of 750 mg of sulphadimidine. Four weeks later, each subject was assigned four different doses of sulphadimidine. The acetylator phenotype was classified for each dose as rapid if the percentage of acetylated sulphadimidine in the post dose 5-6 hour urine is more than 70% and as slow if less than 70%. The results indicate a clear separation into two phenotypes, even with the smallest dose of the drug. A slow acetylator in the 10 subjects showed a saturation of the acetylation capacity with increasing doses. This trend was not observed in the remaining subjects who were identified as rapid acetylators regardless of the doses. An oral dose of 750 mg of sulphadimidine is suggested as a 'standard' or optimum dose for acetylator phenotype testing. PMID- 1744993 TI - Involvement of nicotinic receptors in the dorsal motor nucleus of the vagus in regulation of gastric motility in rats. AB - Roles of nicotinic receptors in the dorsal motor nucleus of the vagus (DMV) in the regulation of gastric motility were investigated in urethane-anesthetized rats in which an intragastric balloon had been placed. Nicotine (0.1 nmole) microinjected into the DMV but not the nucleus ambiguus induced dual changes, a decrease followed by an increase in gastric motility. Administration of 0.1 nmole of hexamethonium into the DMV significantly inhibited the decrease in gastric motility induced by intravenously administered nicotine. PMID- 1744994 TI - Extracellular ATP stimulates steroidogenesis in bovine adrenocortical fasciculata cells via P2 purinoceptors. AB - Effects of ATP and other purine derivatives on steroidogenesis in primary cultured bovine adrenocortical fasciculata cells were examined. At concentrations higher than 1 microM, ATP showed a potent stimulative effect on the cortisol production of the cells. The potency order of the steroidogenic effect of the tested purine derivatives was ATP greater than ADP much greater than adenosine much greater than AMP. alpha,beta-Methylene ATP had no stimulative effect on the steroidogenesis at concentrations as high as 1 mM. Theophylline did not antagonize the steroidogenic effect of ATP. These results suggest that bovine adrenocortical fasciculata cells possess the P2y purinoceptors that are linked to steroidogenesis. PMID- 1744995 TI - Nilvadipine, a new calcium channel blocker, reduces ischemic brain injury in rats. AB - The effects of nilvadipine, a dihydropyridine type calcium channel blocker, on cerebral infarction induced by focal brain ischemia was studied in rats. The area of infarction was measured 24 hr after occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats using triphenyltetrazolium chloride. Nilvadipine, given immediately after MCA occlusion, reduced the area of infarction significantly at doses of 0.32 mg/kg (i.p.) and 3.2, 10 and 32 mg/kg (p.o.). Nicardipine suppressed the area of infarction at a dose of 32 mg/kg (p.o.). The results suggest that nilvadipine is effective against ischemic brain injury. PMID- 1744996 TI - Autoradiographic localization of human calcitonin sensitive binding sites in rat brain. AB - Using 125I-salmon calcitonin (sCT) as a ligand, in vitro autoradiography of rat brain outlined specific anatomical localization of human calcitonin (hCT) sensitive binding sites. The results presented herein show that there are hCT sensitive binding sites in the ventral part of the lateral septum among the sCT specific binding sites distributed throughout the diencephalon. PMID- 1744997 TI - The abilities of specific kappa-opioid agonists, U-50,488H and U-62,066E, to cause antitussive tolerance were lower than that of morphine. AB - We examined whether the chronic administration of selective kappa-opioid agonists could produce antitussive tolerance, in a comparison with the mu-opioid morphine. A certain degree of tolerance to the antitussive effects of morphine appeared in rats treated chronically with this drug. However, chronic administration of U 50,488H and U-62,066E, highly selective agonists for the kappa-opioid receptor, does not result in the development of tolerance to their respective antitussive effects. These results suggest that the ability of kappa-opioid agonists to cause tolerance to their respective antitussive effects was lower than that of a mu opioid agonist. PMID- 1744998 TI - Involvement of protein kinase activation in neurotrophic effects of basic fibroblast growth factor in cultured brain neurons. AB - The influences of K-252a and staurosporine, protein kinase inhibitors, on neurotrophic effects of basic fibroblast growth factor (bFGF) were investigated in dissociated cell cultures of the striatum, hippocampus and cerebellum of fetal rats. Addition of 1 ng/ml bFGF enhanced the survival of cultured neurons of all brain regions tested. Both K-252a (10-200 nM) and staurosporine (1-100 nM) blocked the survival promoting effects of bFGF in a concentration-dependent manner. These results suggest that bFGF exerts its neurotrophic effects through activation of protein kinase(s). PMID- 1744999 TI - Of safe harbors ... and treacherous shoals. PMID- 1745000 TI - The Primary Care Bridging Plan. PMID- 1745001 TI - The EACH Concept. Part I: The basics. PMID- 1745002 TI - Communications with Kansas physicians. AB - The uneven geographic distribution of population, physicians and treatment facilities in Kansas may at times create difficulties in bringing unusual patient problems and needed medical expertise together. Technology currently exists for establishing communication links ranging from live, two-way, audio-video communication connections and computers to the common telephone. This survey indicates that the medical community has great interest in developing functional and cost-effective links. The two campuses of the medical school are working to provide better and broader communications access to the physicians of the state. PMID- 1745003 TI - Medicare/Medicaid fraud and abuse (safe harbors) OIG anti-kickback regulations. PMID- 1745004 TI - Physician to rancher (and back again). Part two. PMID- 1745005 TI - Cutting strokes off at the neck. PMID- 1745006 TI - Angiotensin actions in the kidney: renewed insight into the old hormone. PMID- 1745007 TI - Interleukin-1 beta stimulates human mesangial cells to synthesize and release interleukins-6 and -8. AB - Interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been reported to stimulate human mesangial cells (HMC) to proliferate and synthesize eicosanoids. We have examined whether they also induce HMC to release cytokines. In this study we show that both IL-1 and TNF stimulate HMC to release IL-6 and IL 8. Cycling and quiescent HMC were stimulated with various concentrations of either recombinant IL-1 beta or TNF for 1 to 24 hours. IL-1 beta at doses as low as 6 pg/ml stimulated mesangial cells to synthesize mRNA for both IL-6 and IL-8 as assessed by Northern analysis; mRNA for tubulin remained constant, which demonstrated a specific increase in mRNA. Secretion of IL-6 and IL-8 into the culture medium increased (4.5 to 18 ng/ml and 4 to 40 ng/ml, respectively) measured by ELISAs. TNF had similar effects but only in high concentrations (greater than 100 ng/ml). IL-1 beta did not stimulate cells to proliferate, as measured by 3H thymidine incorporation. TNF caused proliferation but only in concentrations over 100 ng/ml. We conclude that IL-1 beta is a potent stimulator of human mesangial cell production of IL-6 and IL-8, both of which may influence injury in nephritis. TNF also stimulates mesangial cells but only in pharmacological doses. PMID- 1745008 TI - Changes in intracellular sodium during the hydroosmotic response to vasopressin. AB - During vasopressin (VP)-induced water movement, toad urinary bladder epithelial cells undergo unique morphological changes. The osmolality within these responding cells remains relatively stable despite the large transcellular transport of water. We hypothesized that the hydroosmotic response to VP may be associated with a net increase in sodium either as an aid in maintaining the intracellular osmolality or as part of a Na-Ca exchange process. Changes in intracellular sodium (Nai) were monitored over time in individual hemibladders using 23Na NMR. Hemibladders were mounted as bags on glass pipets and filled with deionized water. During NMR studies, the serosal bath consisted of aerated 2.4 mM HCO3 amphibian Ringer's (pH 8.1) made up with 15% D2O containing the shift reagent, dysprosium tripolyphosphate (1 mM). This reagent allowed for visualization of Nai by shifting the extracellular Na signal; it did not affect basal or VP stimulated water flow, short-circuit current, or high energy phosphate metabolism as seen by 31P NMR. Changes in Nai were determined by integrating the area under the unshifted Na peak at each measurement and expressing differences as a ratio relative to baseline. The initial Nai signal from unstimulated hemibladders remained stable in these tissues over at least 180 minutes. Within 30 minutes of VP (20 mU/ml) exposure, however, the Nai peak increased 2.47 times above pretreatment baseline (N = 16, P less than 0.001). The Nai signal returned toward baseline values with removal of VP from the serosal bath but only after approximately 90 minutes. When change in cell shape and water movement were prevented by having isotonic sorbitol in the mucosal bath, VP produced no change in the Nai signal (N = 10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745009 TI - Visceral peritoneum is not essential for solute transport during peritoneal dialysis. AB - The importance of visceral peritoneum in determining transperitoneal solute exchange was studied by determining the influence of evisceration on diffusive solute transport during peritoneal dialysis. Three series of experiments were performed in anesthetized New Zealand White rabbits. Series 1 studies compared solute transport rates from eviscerated rabbits (N = 5) with those from sham operated controls (N = 5). Series 2 studies compared solute transport rates from eviscerated (N = 6) and sham-operated rabbits (N = 5) with application of circumferential abdominal compression to control intraperitoneal pressure and presumably maximize dialysate-peritoneum contact. Series 3 studies compared solute transport rates from sham-operated rabbits (N = 4) with and without applied circumferential abdominal compression. Transperitoneal solute exchange of creatinine and FITC-labeled neutral dextran (15 to 40 A) was equally assessed by both the dialysate to plasma concentration ratio at the end of the exchange and the diffusive permeability-area product of the peritoneum. Evisceration reduced creatinine (P less than 0.001) and dextran (15 to 30 A, P less than 0.05) transport to approximately one quarter that of controls in series 1 rabbits. When circumferential abdominal compression was applied in series 2 rabbits, however, evisceration had no effect on peritoneal solute transport rates. Moreover, circumferential abdominal compression per se had no effect on solute exchange in series 3 experiments. These findings demonstrate that the influence of evisceration on peritoneal solute transport depends on the experimental conditions. These observations further demonstrate that visceral peritoneum is not essential for solute transport during peritoneal dialysis. PMID- 1745010 TI - Morphometric study of glomerular slit diaphragms fixed by rapid-freezing and freeze-substitution. AB - The widths of slit diaphragms in rat glomeruli were quantitatively measured on electron micrographs obtained by the rapid-freezing and freeze-substitution (FS) fixation method and compared to those prepared by conventional chemical fixation procedures, such as tannic acid, glutaraldehyde and osmium tetroxide (TGO) or glutaraldehyde and osmium tetroxide (GO) fixation. When fixed by FS using 2% osmium tetroxide, glomerular slit diaphragms had widths of 33.8 +/- 3.6 nm, but when fixed by TGO or GO they had widths of 47.0 +/- 4.3 and 48.7 +/- 5.5 nm, respectively. The width of slit diaphragms was significantly narrower after cryofixation than after conventional TGO or GO fixation (P less than 0.001). Similarly, the distance between neighboring foot processes at 50 nm from slit diaphragms was significantly narrower after cryofixation (P less than 0.001). The widths were 98.6 +/- 17.1 nm after TGO fixation, 122.0 +/- 29.3 nm after GO fixation and only 54.8 +/- 18.7 nm after FS fixation. These foot processes were significantly broader after FS fixation. The foot processes were 179.2 +/- 59.4 nm in breadth after TGO fixation (P less than 0.001), 188.8 +/- 78.2 nm after GO fixation (P less than 0.01) and 235.1 +/- 87.2 nm after FS fixation. These results suggest that the cytoplasm of foot processes shrinks when the tissue is prepared by conventional chemical fixation methods, and that the broadening of slit diaphragms is an artifact separation of the margins of adjacent foot processes due to shrinkage. We propose that TGO fixation alters the structure of slit diaphragms by causing them to shrink. PMID- 1745011 TI - Red cell trapping and postischemic renal blood flow. Differences between the cortex, outer and inner medulla. AB - The distribution of blood flow in the rat kidney after 60 minutes of renal ischemia was studied by single-fiber laser-Doppler flowmetry. Blood flow in superficial cortex and inner medulla was measured with a probe directed towards the kidney surface and exposed papilla, respectively. Outer medullary blood flow was measured with a probe introduced through the renal core. After ischemia the blood flow decreased to 60% of the preischemic value (P less than 0.01) in superficial cortex and to 16% (P less than 0.01) in outer medulla, while inner medullary blood flow increased paradoxically to 125% (P less than 0.01). There was extensive trapping of red blood cells (RBC) in the outer medulla, but not in the inner medulla or cortex. The fractional RBC volume as measured by radiolabeled RBCs was 21% in the inner stripe of the outer medulla, but 2% in this area in a normal kidney. To investigate the influence of RBC trapping on intrarenal distribution of blood flow after ischemia, the hematocrit was reduced from 46% to 31% by isovolemic hemodilution. When performed before ischemia, this maneuver almost completely abolished RBC trapping. In this group blood flow in both outer and inner medulla was almost unchanged after ischemia, while superficial cortical blood flow decreased to 66% (P less than 0.01) of the pre ischemic value. It is concluded that RBC trapping in the outer medulla causes a large decrease in blood flow in this area and, at the same time, shunting of blood to the inner medulla. In the absence of RBC trapping, blood flow of both outer and inner medulla is well preserved after ischemia. PMID- 1745012 TI - Early renal medullary hypoxic injury from radiocontrast and indomethacin. AB - We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model. PMID- 1745013 TI - Renal entactin (nidogen): isolation, characterization and tissue distribution. AB - Entactin/nidogen (E/N) was isolated from bovine renal tubular basement membrane. Apparent molecular weight, amino acid composition, and molecular configuration by electron microscopy rotary shadowing were similar to that of nidogen from EHS mouse tumor. The identity of bovine E/N was confirmed using a thrombin derived peptide, the sequence of which corresponded to a region within mouse and human E/N. Monoclonal and polyclonal anti-E/N antibodies were used to determine the distribution of E/N in human kidney by immunofluorescent and immunoelectron microscopy. E/N was present in all renal basement membranes and was distributed through the full width of the glomerular basement membrane (GBM) with accentuation along its epithelial aspects. E/N distribution was similar to that of novel collagen chain alpha 3(IV) NC domain in the GBM. In the mesangium, E/N was distributed mainly in the peripheral mesangial region that is bounded by the GBM, while classical collagen chain alpha 1(IV) NC as present diffusely throughout the mesangium. In the developing nephron, E/N was present in basement membranes of the ureteric bud, primitive vesicle and S-form. In all instances, E/N co-localized with laminin B2 chain. Prominent E/N detection within the mesangium was observed in diseases where mesangial expansion was present. This process was also seen in early diabetic nephropathy, but disappeared with disease progression. However, all thickened diabetic renal basement membranes showed an increase in E/N which was also present in Kimmelstiel-Wilson lesions. E/N was observed in the GBM "spikes" of membranous glomerulonephritis and in epithelial crescents associated with various disorders. The association between E/N, laminin and type IV collagen chains observed in the normal kidney were maintained in disorders with altered E/N distribution. We could not detect any changes in the distribution of E/N in other acquired and hereditary kidney diseases. These observations reflect the involvement of E/N in the structure and disease alteration of renal basement membranes and mesangial matrix. PMID- 1745014 TI - Mesangial cell behavior in a three-dimensional extracellular matrix. AB - To understand the role of mesangial matrix in regulating responses of mesangial cells (MCs), particularly as a cause of disease, we examined the behavior of MCs cultured in a three-dimensional extracellular matrix (ECM). Mouse and rat MCs were incorporated into ECM composed of type I collagen gel matrix (CGM) and basement membrane-type gel matrix (BGM), and their shape and proliferation were assessed. The effect of gel matrix on MC migration was also studied. MCs exhibited marked elongation and proliferation in CGM, whereas these behavior were inhibited by increasing the ratio of BGM. Although CGM allowed MC migration, BGM restricted it to a great extent. To identify the cause of our findings, we examined the effects of ECM components in our experimental system. Laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin) were each mixed separately with CGM at a concentration of 50 micrograms/ml gel. Whereas fibronectin promoted MC elongation and proliferation, and laminin inhibited MC migration, type IV collagen and heparin-like proteoglycans inhibited all three activities of MCs. Our findings suggest that basement membrane-type mesangial matrix is important in regulating the behavior of MCs in vivo. PMID- 1745015 TI - Impaired insulin secretion of aging: role of renal failure and hyperparathyroidism. AB - Available data indicate that insulin secretion is impaired with aging. Almost all the studies that examined insulin secretion by old animals did not take into consideration the state of renal function or the blood levels of parathyroid hormone (PTH). Old animals may have chronic renal failure (CRF) and secondary hyperparathyroidism, and both of these conditions impair insulin secretion. It is possible, therefore, that the impaired insulin secretion of aging is not due to old age per se, but rather to associated CRF and excess PTH. The present study examined this issue in adult (6 month old) and senescent rats (2 year old) with and without CRF and excess PTH. Senescent rats without CRF had normal renal function and normal blood levels of PTH, and the values were not different from those observed in adult rats. Creatinine clearance in senescent rats with CRF was significantly (P less than 0.01) lower and serum levels of PTH were significantly (P less than 0.01) higher than in senescent animals without CRF and than in the adult rats as well. Only the senescent rats with CRF displayed glucose intolerance during intravenous glucose tolerance test. For any given level of blood glucose, plasma insulin levels were lower in senescent rats with CRF than in the adult rat or senescent animals without CRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745016 TI - Isolation of a novel complement regulatory factor (GCRF) from glomerular epithelial cells. AB - Cultured rat glomerular epithelial cells (GEC) are able to prevent both antibody directed and spontaneous (alternative pathway) complement activation. In this study, a novel complement regulatory factor (GCRF) was isolated from GEC. The ability to accelerate the decay of alternative pathway C3/C5 convertases formed on sheep erythrocytes (EC3bBbP) was used to guide purification. GEC were solubilized in Triton X-114 and GCRF was recovered in the aqueous phase. Complement inhibitory material also was present in the culture supernatant, which likely represented GCRF. By Mono Q anion exchange chromatography, GCRF eluted at greater than or equal to 0.6 M NaCl and by Superose 6 size-exclusion chromatography, it had a Kav less than or equal to 0.3. GCRF reduced the t1/2 of EC3bBbP from 128 minutes in buffer alone to 41 minutes in 3 micrograms/ml GCRF protein, and also prevented formation of EC3bBbP in a dose-dependent fashion. Digestion with chondroitinase ABC, neuraminidase, or trypsin, but not with heparitinase or chondroitinase AC significantly reduced the activity and size of GCRF, demonstrating that it is a sialic acid-containing dermatan sulfate proteoglycan. Thus, cultured rat GEC synthesize and secrete into the medium, GCRF, a dermatan sulfate proteoglycan with complement inhibitory activity. PMID- 1745017 TI - Glomerular renin synthesis and storage in the remnant kidney in the rat. AB - The intrarenal renin-angiotensin system can exert local control of the nephron and its circulation. In the subtotally nephrectomized model of chronic renal disease in the rat, angiotensin appears to play a prominent role in glomerular function. Glomeruli in this model demonstrate greater staining for intraglomerular renin by immunofluorescence microscopy than do those in control rats. Glomeruli from remnant nephrons contain increased renin content. Also, glomeruli from remnant nephrons contain an increased proportion of the mRNA for renin. Adriamycin-induced nephrosis did not evoke the same degree of renin staining and did not lead to increased glomerular expression of the renin gene, findings that argue against permselective defects and glomerular trapping as the sole cause of the glomerular renin in the remnant kidney model. Thus, renin synthesis and accumulation occur in the remnant glomerulus and this migration may underlie in part the dependence of glomerular function on the renin-angiotensin system in this model. PMID- 1745018 TI - Role of ornithine decarboxylase for proliferation of mesangial cells in culture. AB - To elucidate the role of polyamine metabolism in the regulation of mesangial cell growth, we examined the involvement of ornithine decarboxylase (ODC), the rate limiting enzyme for polyamine synthesis, in the mitogenesis of cultured rat mesangial cells (MCs). Resting MCs, stimulated with fetal calf serum (FCS 10%), showed an induction of ODC activity from undetectable values in resting cells to mean = 5035 nmol CO2/10(10) cells.hr (range 3157 to 7154, N = 5), which is 25 fold above the detection limit. We found a single peak of ODC activity eight to ten hours after stimulation, declining to 22 to 34% of peak levels after 24 hours. 3H-thymidine (TdR) uptake, an S-phase marker of MC replication, peaked at 24 hours, reaching 10.7-fold values of resting MCs. ODC mRNA levels were low in resting cells. After serum stimulation there was a two- to 10-fold increase in ODC mRNA with a maximum after six hours. ODC activity with similar kinetics but lower peak levels was also induced by incubating MCs with mitogens, such as platelet-derived growth factor (PDGF-AB 20 ng/ml), arginine vasopressin (AVP 10( 7) M), phorbol myristate acetate (PMA 10(-7) M), interleukin 1 alpha and beta (IL 1 alpha 10 U/ml, IL-1 beta 10 U/ml). In the presence of alpha difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ODC, the growth rate of MCs, assessed by cell counts and by 3H-TdR uptake, was markedly reduced by 62 to 100%. This antiproliferative effect of DFMO could be reversed by addition of putrescine, the reaction product of ODC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745019 TI - Distribution of epidermal growth factor in the kidneys of rats exposed to amikacin. AB - The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.p. twice a day. One hour before termination, each rat received an i.p. injection of [3H] thymidine to evaluate DNA synthesis in renal tissue. After sacrifice, the kidneys were processed for morphological (semithin and paraffin sections) and biochemical analysis (measurement of DNA synthesis by [3H] thymidine incorporation in vivo). Amikacin induced in proximal tubules a dose-related lysosomal phospholipidosis, which was assessed by the morphometric evaluation of altered lysosomes ("myeloid bodies") on semithin section. However, frank evidence of acute tubular necrosis was only observed in rats receiving amikacin at a daily dose of 200 mg/kg. Concomitantly with the development of tubular necrosis, there was a rise in the rate of cell turnover, reflected by an increase of DNA synthesis in renal tissue. This sign of tubular regeneration was accompanied by a redistribution of EGF immunoreactivity, as revealed by immunocytochemical staining. Within renal cortex of control rats, EGF immunoreactivity predominantly appeared in distal tubules and collecting ducts (97% of examined tubular sections). In contrast, in treated animals where the renal cortex displayed evidence of tubular necrosis/regeneration, EGF immunoreactivity was frequently associated with proximal tubules (more than 30% of examined tubular sections, as compared to 3% in controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745020 TI - Sigmoidal relationship between calcitonin and calcium: studies in normal, parathyroidectomized, and azotemic rats. AB - Calcitonin secretion is stimulated by acute hypercalcemia. Furthermore, in the rat, the calcemic response to parathyroid hormone (PTH) is decreased by calcitonin stimulation. However, in renal failure, it is not known if an increase in the serum calcium concentration within the physiologic range of serum calcium stimulates calcitonin and whether the increased calcitonin decreases the calcemic response to PTH. In the present study, four groups of pair-fed rats were evaluated: normals (N); parathyroidectomy (PTX); and two groups with renal failure (RF)--basal serum calcium less than 8.5 mg/dl (RFa) and basal serum calcium greater than 8.5 mg/dl (RFb). Hypocalcemia was induced by parathyroidectomy or in the RFa group, by a high phosphate diet. Increases in the serum calcium were produced by a 48 hour infusion of rat 1-34 PTH. In the RFa and PTX groups, stimulation of calcitonin was observed as the serum calcium increased from hypocalcemia to normal levels of calcium (P less than 0.01). In all four groups, increasing the serum calcium from normal levels to hypercalcemia increased the serum calcitonin level (P less than 0.05). The relationship between serum calcitonin and calcium was best expressed as a sigmoidal curve. In the two groups with basal hypocalcemia, PTX and RFa, the calcitonin-calcium curve was shifted to the left of the N and RFb groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745021 TI - Effect of mesangial cell lysis and proliferation on glomerular hemodynamics in the rat. AB - To elucidate an involvement of mesangial cells in the regulation of glomerular hemodynamics, renal micropuncture techniques and glomerular morphometry were employed in Munich-Wistar rats with mesangial cell lytic or proliferative lesions induced by administration of an antibody reactive with Thy-1.1-like antigens on the mesangial cell surface. The antibody-induced mesangial cell lysis at day 1 resulted in a significant decrease in glomerular ultrafiltration coefficient, leading to reduction in single nephron glomerular filtration rate (SNGFR) in spite of a significant increase in both glomerular hydrostatic pressure and single nephron plasma flow (SNPF). During the antibody-induced proliferative lesion at day 6, glomerular ultrafiltration coefficient and SNGFR remained reduced; however, SNPF was now decreased. Morphometric analysis showed the enlargement of capillary luminal volume and the development of new open space in the mesangium accessible for blood flow in the mesangial cell-lytic glomeruli at day 1. An increase in mesangial cell volume was found in the proliferative glomeruli at day 6. The total area of peripheral glomerular basement membrane, presumed as the probable filtration area, was unchanged in these glomeruli. These results indicate that mesangial lesions decrease glomerular ultrafiltration coefficient, and suggest that mesangial cells participate in regulation of glomerular filtration rate. PMID- 1745022 TI - Acute intradialytic well-being: results of a clinical trial comparing polysulfone with cuprophan. Bergamo Collaborative Dialysis Study Group. AB - We conducted a multicenter, randomized, double-blind, controlled clinical trial to compare the effects of a synthetic, high-flux polysulfone membrane with a standard cuprophan one on acute clinical complications during a diffusive dialysis procedure. The principal end-point, that is, the number of hypotensive episodes, was similar in polysulfone (39; 23.8%) and cuprophan (32; 19.5%). Likewise, no significant difference was found between the two membranes as far as the secondary end-point was concerned, that is, the effect on headache, nausea, pruritus and sense of well-being. We conclude that high-flux polysulfone, acutely used in standard diffusive dialysis, has no favorable influence on hypotensive episodes and does not affect some typical dialysis-related symptoms any differently from cuprophan membrane. The need is stressed for well-controlled studies specifically designed to assess the worth of new dialysis techniques and materials that may vastly raise the cost of dialysis treatment. PMID- 1745023 TI - Decreased postheparin lipolytic activity in renal transplant recipients with cyclosporin A. AB - The patterns of hyperlipidemia in renal transplant recipients (RTRs) are more variable than in the uremic state, showing increases in both very low-density lipoprotein (VLDL) and low density lipoprotein (LDL). This has been attributed, at least in part, to immunosuppressive therapy, especially to treatment with corticosteroids. Postheparin lipolytic activity (PHLA) was determined in 28 RTRs. Sixteen patients presenting with hyperlipidemia comprised group A, who were aged 49.8 +/- 13.5 years, and had a cholesterol of 8.24 +/- 1.86 mmol/liter, triglycerides of 6.02 +/- 3.33 mmol/liter. Twelve patients presenting cholesterol and triglyceride values within the normal range were in group B, and were aged 48.6 +/- 13.3 years. All RTRs received cyclosporin A (CsA) twice daily orally, which were divided in two equal doses and adjusted to provide CsA blood trough levels (RIA) in a range of 250 to 350 ng/ml. Twenty-one RTRs were additionally treated by alternate-day corticosteroids, whereas seven patients had CsA on their sole immunosuppressive agent. PHLA (mumol free fatty acids/ml/hr, given 10 and 20 min after 100 U/heparin kg body wt intravenously) was commonly reduced in RTRs (group A at 10/20 min: 5.6 +/- 1.1/5.26 +/- 1.2; group B: 8.26 +/- 2.91/8.38 +/- 3.44) as compared to the values obtained in healthy controls (15.3 +/- 2.9/17.2 +/- 5.0). This was mainly due to a reduction of the activity of the hepatic triglyceride lipase, and to a minor extent to a reduced activity of peripheral lipoprotein lipase. There was no statistically significant difference of PHLA in RTRs with or without corticosteroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745024 TI - Epidemiologic study of analgesic abuse: mortality study in 7275 working women (1968-1987). AB - In a prospective, longitudinal investigation over a period of 20 years in 7275 working women 30 to 49 years old, we examined the effect of the ingestion of analgesics on cause-specific mortality. Evidence of intake of phenacetin and salicylate containing analgesics was obtained at a urine screening in 1967 and was shown to relate to intake between 1968 to 1978. Life table analysis of the effect of phenacetin intake on overall mortality showed significant differences between the groups of women with intake (N = 613) versus no intake (N = 4175): for total [relative risk (RR) = 2.1, P less than 0.001], urorenal (RR = 24.4, P less than 0.001), cardiovascular (RR = 4.5, P less than 0.001), and cancer mortality (RR = 1.9, P less than 0.001). No significant effects on overall or cause-specific mortality were found for salicylate intake. These results make a causal relationship between the amount of analgesic containing phenacetin consumed and the risk of death from urorenal disease likely. Furthermore, the data show an elevated risk for cardiovascular disease and cancer for phenacetin intake. No such relationships are demonstrable for the use of salicylate. PMID- 1745025 TI - Role of platelet activating factor in gentamicin and cisplatin nephrotoxicity. AB - The present study was undertaken to evaluate the effects of platelet activating factor (PAF) antagonists on nephrotoxicity induced by gentamicin (GENTA) and cisplatin (DDP) in rats. PAF infusion provoked a 56% decline in single nephron (SN) GFR due to a decrease in glomerular plasma flow (QA, 55%), glomerular transcapillary hydraulic pressure (delta P, 13%), and glomerular ultrafiltration coefficient (Kf, 37%). Four days after a single dose of DDP (6 mg/kg, i.p.) we observed non-oliguric acute renal failure (ARF) with reduced SNGFR (45%), QA (46%) and delta P (10%) and unchanged Kf. GENTA administration for 10 days (40 mg/kg, i.p. daily) induced a decline in SNGFR (40%), QA (41%) and Kf (41%). Chronic treatment with a GENTA + PAF antagonist (BN 52021) partially prevented the decline in SNGFR (22%) by an amelioration in QA (25%) and Kf (13%). However, simultaneous treatment with DDP and BN 52063 completely prevented the ARF induced by DDP, normalizing all parameters of renal function. Thus, PAF may be a potential mediator involved in the nephrotoxicity induced by GENTA and DDP. PMID- 1745026 TI - Long-term results of renal transplantation in children. AB - The results of renal transplantation in 37 children, 3 through 16 years of age, who received transplants prior to June, 1970 in our center, were examined. Twenty three received kidneys from living-related donors and 14 received kidneys from cadaver donors. Patient survival rates were 78% at 10 years and 68% at 20 to 26 years. Graft survival rates were 56% at 10 years, 31% at 20 years, and 23% at 22 to 26 years. Twenty children received on or more retransplants. At follow-up, 23 (62%) of the patients had functioning grafts and two (5%) were undergoing dialysis. Cataracts, hypertension, and aseptic necrosis of bone were the most common medical complications and most of the patients were more than two standard deviations below average height. Most enjoyed good rehabilitation, however: more than 70% were employed or performing full time housework, more than 50% were married, 24% had children, and all had normal activity at least part of the time. These results, achieved with immunosuppressive methods now considered obsolete, indicate that renal transplantation is a satisfactory long-term treatment for children with renal failure. PMID- 1745027 TI - Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. AB - To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry. Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine less than 500 mumol/liter (N = 17), or greater than 500 mumol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases. PMID- 1745028 TI - Angiotensin II receptor-mediated proliferation of cultured human fetal mesangial cells. AB - Accumulating evidence suggests that angiotensin II (Ang II) may play an important role in renal growth and glomerular development. During nephrogenesis, a complex relationship between the capillary and renal mesangium develops. Since the mesangial cell is a centrally-located pericyte with contractile, endocrine, and immune modulating functions, it may play a unique role in maintaining normal glomerular function. Therefore, we examined whether Ang II affects proliferation of human fetal mesangial cells in vitro and compared these findings to mesangial cells isolated from adult kidney. In these primary isolates, we studied the relationship between Ang II receptors and the mitogenic activity of angiotensin. Scatchard analysis of the binding of 125I[Sar1,Ile8]Ang II to subconfluent cultured human fetal mesangial cells revealed the presence of one class of binding sites with a Kd of 1.25 nM and a Bmax of 70 fmol/1 x 10(5) cells. Ang II receptors on adult mesangial cells had similar binding kinetics with a Kd of 1.6 nM and Bmax of 65 fmol/10(5) cells in subconfluent culture. In subconfluent culture of fetal mesangial cells, Ang II increased [3H]thymidine incorporation by 130% (P less than 0.005). In subconfluent culture of adult mesangial cells, Ang II increased [3H]thymidine incorporation by only 35% (P less than 0.05). In confluent culture of fetal mesangial cells, Ang II receptor number and mitogenic response were reduced. The Ang II antagonist [Sar1,Ile8]Ang II (1 microM) inhibited the mitogenic response of fetal mesangial cells to Ang II. Ang II increased fetal mesangial cell number by 25% (after 4 days) in serum-free medium supplemented with insulin or supplemented with insulin and 1% Nutridoma (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745029 TI - Renal ammoniagenesis in humans with chronic potassium depletion. AB - Renal ammonia production and distribution and ammonia precursor utilization were evaluated in eight patients with chronic potassium depletion (CPD) and aldosterone-producing adenoma and in 20 controls. In CPD, urinary ammonia excretion and ammonia added to renal venous blood were about twofold higher than in controls; thus, total ammonia production was significantly augmented (88.0 +/- 10.3 mumol/min.1.73 m2 vs. 45.0 +/- 2.6 in controls). Total ammonia production was inversely correlated with serum potassium and directly correlated with urine flow. Stepwise multiple regression analysis showed that both factors, mainly serum potassium, significantly influence ammonia production and account for 61.4% of variations in ammonia production. Renal extraction of glutamine was significantly increased (56.6 +/- 5.9 mumol/min.1.73 m2 vs. 34.6 +/- 3.1 in controls), and this could account for ammonia production. The ratio of urinary ammonia excretion to total ammonia production, an index of the intrarenal ammonia distribution, was similar in patients and controls, and was significantly correlated with urine pH and true renal blood flow (RBF). Stepwise multiple regression analysis showed that RBF, urine pH and urine flow also significantly affected ammonia distribution. However, these factors accounted for only 41.7% of variations in intrarenal ammonia partition, urine pH having a minor role. We conclude that in patients with CPD other factors besides urine pH, urine flow and RBF intervene in the ammonia partition between urine and blood. PMID- 1745030 TI - Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia. AB - To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive responses are intact. Because MA stimulates muscle proteolysis, this study examined the hypothesis that in CRF complicated by MA, the adaptation to LPD may be impaired, inducing a nitrogen wasting state. Six adults with CRF (mean GFR: 12.8 +/- 1.5 ml/min) and MA (mean serum bicarbonate: 17.0 +/- 1.0 mM/liter) receiving an unrestricted diet (protein intake: 1.2 g/kg body wt/day) were converted to an isocaloric LPD (protein: 0.6 g/kg body wt/day). Two weeks later total urinary nitrogen losses decreased, but skeletal muscle protein catabolism (SMPC), assessed from the urinary 3-methyl histidine:creatinine ratio, increased, demonstrating impairment in the adaptive down-regulation of SMPC. The LPD was continued for a further two weeks and MA was corrected with oral sodium bicarbonate (mean serum bicarbonate: 24.3 +/- 1.2 mM/liter). Correcting MA decreased SMPC to a level below that measured prior to protein restriction. The decreased SMPC was paralleled by further decreases in urinary nitrogen losses, confirming that MA impaired nitrogen utilization. It is concluded that MA can override the expected metabolic adaptive response to a LPD. The associated impairment of nitrogen utilization not only diminishes the efficacy of the diet, but also accelerates the loss of lean body mass. PMID- 1745031 TI - Anti-interleukin-1 alpha autoantibodies in hemodialysis patients. AB - IL-1 activity is increased in hemodialysis patients and interest has recently been focused on IL-1 antagonism in various clinical settings. We studied the presence of anti-IL-1 alpha autoantibodies in sera from 49 hemodialysis patients, 159 kidney graft recipients and 89 chronic renal failure patients without renal replacement therapy. Within the three month study period 32.6% of the hemodialysis patients were found to present with anti-IL-1 alpha autoantibodies, in contrast to 5.6% of kidney graft recipients, 8.9% of chronic renal failure patients, and only 1.4% of healthy subjects. The presence of these autoantibodies was neither associated with primary kidney disease nor with the type of dialysis membrane we used. In addition, in antibody positive patients a pronounced increase of IL-1 alpha serum levels within a dialysis session from 14.8 +/- 4.7 pg/ml to 26.4 +/- 11.2 pg/ml (P less than 0.0005) was observed, contrasting to the more even increase from 14.1 +/- 3.1 pg/ml to 19.3 +/- 12.7 pg/ml (P less than 0.05) in the antibody negative group. Neither clinical symptoms due to adverse effects of IL-1 alpha nor some influence on erythropoiesis mediated by IL 1 alpha could be envisaged. Thus, we believe, that anti-IL-1 alpha autoantibodies, present in high frequency in hemodialysis patients, have a neutralizing effect on IL-1 alpha in these patients. PMID- 1745032 TI - Mechanisms of diabetic hyperfiltration. PMID- 1745033 TI - [Current treatment protocol in cardiovascular diseases in childhood. 1: Heart failure, diseases in the neonatal period, congenital heart defects. 2: Arrhythmias, carditis, cardiomyopathies, shock, hypertension]. AB - It is given an overview about actual strategies of the treatment of children suffering from heart diseases. Partly proven drugs are given in an optimized doses e.g. digoxin and digitoxin where as other new drugs and therapeutic principles are introduced e. g. catecholamines and vasodilator agents, antiarrhythmic drugs or electrotherapy and antiarrhythmic surgery. Various functional disturbances of the cardiovascular system can occur in the newborn period. New diagnostic principles especially echocardiography with doppler sonography, holter monitoring and exercise testing have lead to better therapeutic regimens. Heart catheterizations have new therapeutic tools like the balloon valvuloplasty of a stenotic pulmonic valve. At least the advances of cardiac surgery have lead to a shift of the time of correction to early childhood. Two step interventions are more and more removed and the related children and their families will have a better outcome and a better life quality. PMID- 1745034 TI - [Neonatal nutrition with enriched human milk. EOPROTIN 60 in comparison with human albumin]. AB - The influence of feeding fresh human milk supplemented either with EOPROTIN (n = 13) or human albumin (n = 15) on biochemical parameters and growth were studied in preterm infants with gestational ages below 32 weeks p.m. up to the 42nd day of postnatal life. In both feeding groups the intakes of protein, energy and electrolytes were similar. The serum concentrations of bile acids, alpha-amino nitrogen and prealbumin, the renal excretion of total nitrogen, alpha-amino nitrogen, urea and ammonia as well as the growth in weight and length were studied in all infants. The supplementation of the fresh human milk with EOPROTIN results in significant lower serum concentrations of alpha-amino-nitrogen (1.56 +/- 0.21 vs 2.03 +/- 0.27 mmol/l; p less than 0.01), higher serum concentrations of prealbumin (89.8 +/- 20.3 vs 72.7 +/- 13.3 mg/l; p less than 0.02), and lower urinary excretion of total nitrogen (7.4 +/- 0.9 vs 8.9 +/- 1.1 mmol/kg/day); if compared to the results found in the infants fed human albumin supplemented human milk. The higher nitrogen retention in the EOPROTIN than in the human albumin fed infants was associated by a significant higher growth in weight (16.6 +/- 1.4 vs 13.7 +/- 1.9 g/kg/day; p less than 0.01) as well as in length (1.02 +/- 0.08 vs 0.87 +/- 0.1 cm/week; p less than 0.01). The results indicate that the bioavailability of EOPROTIN is higher than that of human albumin. The observed differences in the nutritional response between the two human milk supplements may be based on differences in the amino acids composition which is in EOPROTIN adapted to the nutritional available part of the protein in human milk. PMID- 1745035 TI - [Obstructive respiratory tract diseases in children and Parvovirus B19 infections]. AB - Acute respiratory diseases (ARD) due to parvovirus B 19 infection can be observed relative frequently in children. In 21 children (infants, toddlers and school children) we have seen acute or prolonged obstructive bronchitis/bronchiolitis (15 infants), acute subglottic laryngitis (3 toddlers) and acute asthmatic attacks (3 children of school age) in connection with parvovirus B 19 infection. Other respiratory viruses (adeno-, influenza, parainfluenza and RS-virus) could be excluded as agents causing the ARD. We suggest that parvovirus B 19 can provoke ARD with obstructive ventilatory disturbances of the upper or lower airways in children with a specific endogenous predisposition (small or unstable bronchial walls, or bronchial or tracheal mucosal hyperreactivity). PMID- 1745036 TI - [Mental development of children with congenital hypothyroidism--a neuropsychological follow-up study]. AB - 57 children with congenital, clinical diagnosed hypothyroidism were assessed with the Luria-Nebraska-Neuropsychological Battery-Children's Revision. The results of the psychomotor assessment were in conformity with the mental development. Univariate correlations between begin of therapy and mental development were not found in all groups. PMID- 1745037 TI - [Studies on the predictive value and prognostic significance of compliance measurements in artificially ventilated newborn infants]. AB - In 29 mechanical ventilated preterm infants the compliance of the respiratory system (Crs) was determined. Newborn infants with severe respiratory distress syndrome show a decreased Crs. A significant correlation could be proved between the Crs and the pCO2 as well as the inspiratory pressure. The second estimation of the Crs after 48 hours refers to the prognosis of the ventilated newborn infants. PMID- 1745038 TI - [Acrocephalosyndactylia of the Apert Type (McK 10120)]. PMID- 1745039 TI - [Carpenter syndrome (McK 20100, 20102, 27235)]. PMID- 1745040 TI - A study on the brain structures related to conditioned emotional response by means of [14C]2-deoxy-D-glucose method. AB - Brain structures activated during conditioned emotional response were studied by means of the [14C]2-deoxyglucose method. The experimental (CSE) animals were conditioned with paired 25 25-sec-long flicker sequences (CS) and 1-sec-long 150 V AC electric shocks (US), while the control (CSC) animals were given only 25 CS sequences. Average densities of a unit square (200 microns x 200 microns) of 47 nuclei or cortical areas in the left hemisphere were obtained from an autoradiogram and the optical density ratio (ODR), which is the relative optical density of each structure to that of the corpus callosum, was calculated. Comparison of ODRs of each structure from both groups revealed a significant increased uptake of [14C]2-deoxyglucose (P less than 0.05, Mann-Whitney U-test) in the caudal portion of area 10, area 2, area 18 and the hippocampal formation. PMID- 1745041 TI - A novel type of regulatory protein for the GDP/GTP exchange reaction of smg p25A, a ras p21-like small GTP-binding protein, in bovine brain cytosol. AB - A regulatory protein for smg p25A, a ras p21-like small GTP-binding protein, was purified to near homogeneity from bovine brain cytosol. This regulatory protein, named smg p25A GDP dissociation inhibitor (GDI), regulated the GDP/GTP exchange reaction of smg p25A by inhibiting the dissociation of GDP from and the subsequent binding of GTP to it. Both the GDP- and GTP-bound forms of smg p25A bound to synaptic plasma membranes and vesicles. smg p25A GDI formed a complex with the GDP-bound form of smg p25A and thereby inhibited its binding to membranes and furthermore induced the dissociation of the prebound protein from the membranes. These results indicate that smg p25A GDI is a novel type of regulatory protein for the GDP/GTP exchange reaction and the intracellular translocation of smg p25A. PMID- 1745042 TI - Isolation and characterization of protein kinase C from rat brain synaptosome cytoskeleton. AB - Synaptosomes prepared from brain tissues are known to retain morphological and functional characteristics of the nerve ending. Little information is available, however, as to the biochemical events underlying synaptogenesis and transmitter release. Increasing body of evidence suggests that protein kinase C (PKC) plays crucially important roles through phosphorylation of membrane proteins such as GAP-43 (for 43-kDa growth-associated protein) and 87-kDa MARCKS (for myristoylated, alanine-rich C kinase substrate) in many aspects of the neuronal function. Among them, arrangement of membrane cytoskeletal protein is proposed to be one of the primary sites of PKC action. The present study is an attempt to isolate and characterize PKC associated with synaptosomal membrane cytoskeleton. Rat brain synaptosomal Triton X-100 insoluble elements (cytoskeleton) contains specific [3H]phorbol dibutyrate binding activity and 78-kDa protein which reacts with an antibody against beta II-PKC subspecies. Although 78-kDa protein could not be solublized by the treatment with various ionic and non-ionic detergents and/or high concentrations of salts such as NaCl and LiBr, the fragment of 78-kDa protein was produced and solublized from cytoskeleton by limited proteolysis with calpain II, which cleaves PKC at one or two specific sites of the enzyme to produce catalytic and regulatory fragments. The solubilized 46-kDa fragment was identical with the catalytic fragment of beta II-PKC. The results indicate that this PKC subspecies is tightly associated with the cytoskeletal network of synaptic membranes. PMID- 1745043 TI - Suppressive effect of 1,25(OH)2D3, and glucocorticoids on production of tumor necrosis factor-alpha by human peripheral blood adherent cells. AB - Effect of 1,25(OH)2D3 and glucocorticoids on production of TNF-alpha by human peripheral blood adherent cells (HPBAC) was investigated. TNF-alpha was measured by ELISA method using monoclonal antibody against human recombinant THF-alpha. Maximal TNF-alpha production by HPBAC was observed in 4 to 8 hr after incubation when these cells were cultured for 24 hr with 10 micrograms/ml lipopolysaccharide (LPS), 10 ng/ml 12-o-tetradecanoyl-phorbol-13-acetate (TPA) and 10(-5) M indomethacin (INDM). When graded concentration of 1,25(OH)2D3 was added to HPBAC in the presence of above stated dose of LPS, TPA and INDM, a significant suppression of TNF-alpha production was first observed at the concentration of 10(-8) M (P less than 0.05). Similar significant suppressive effect was also observed by adding hydrocortisone and dexamethasone at the concentration of 10( 8) M (P less than 0.05) and 10(-7) M (P less than 0.05), respectively. These results may suggest that 1,25(OH)2D3 has the same inhibitory effect on monocyte/macrophage function as glucocorticoids. PMID- 1745044 TI - Axillary dissection in breast cancer: when, why, how much, and for how long? Another operation soon to be extinct? PMID- 1745045 TI - An immunological aspect of melanoma and its potential application in adjuvant therapy. AB - In an attempt to understand some of the natural immunological characteristics of cutaneous melanoma so that we can plan justifiable immunotherapeutic approaches, 23 patients were studied. The autologous leukocyte migration inhibition assay was utilized to assess in vitro their tumor-specific cellular immunity. This assay was specifically used because when presensitized lymphocytes are exposed to the same antigen, they release lymphokines which inhibit the natural migration of the leukocytes. All the patients were staged pathologically according to the TNM system. Twelve of them had regional metastasis, i.e., stage III, and underwent regional lymphadenectomy. The other 11 had distant metastases, i.e., stage IV disease, and all their gross tumors were resected. These 23 patients were the source of tumor material and peripheral blood. Fresh autologous leukocytes were obtained for the assays, from each patient, on the day of surgery and prior to the administration of the preoperative medications. These were tested in vitro, on the same day, with freshly prepared autologous tumor extracts as the source of autologous tumor antigens. The results revealed that the preoperative leukocytes of patients with stage III melanoma expressed hypersensitivity to their tumors, with significant inhibition of their leukocyte migration, compared to those with distant metastases who expressed no such sensitivity, P = 0.012. Such hypersensitized lymphocytes may be capable of producing more efficient lymphokine activated killer (LAK) cells for an effective adjuvant adoptive immunotherapy. PMID- 1745046 TI - Functional outcome in patients treated with surgery and irradiation for soft tissue tumours. AB - One hundred five consecutive patients underwent surgical resection and adjuvant irradiation in treatment of soft tissue sarcoma or aggressive fibromatosis. All patients were entered in a prospective study evaluating functional outcome and 88 patients were examined at 12 months following surgery. Outcome was characterized using the Enneking system as well as documenting employment/recreational status and limb edema. Sixty-eight of 88 patients had functional scores of 21 or better (out of a possible total of 35). Forty-four patients were serially evaluated at 12 and 24 months and there was no difference in their outcome at the 2 time points. Univariate analysis demonstrated that large tumour size, postoperative complications, and neural sacrifice were associated with poor functional outcome. PMID- 1745047 TI - Diagnosis and management of sacrococcygeal chordoma. AB - Chordoma is a rare, slow-growing but locally aggressive malignant tumor derived from the primitive notochord and located along the axial skeleton. Between 1973 and 1991, of 15 patients with chordomas treated at the Medical College of Virginia, eight originated in the sacrococcygeal area. There was a median one year interval between the onset of symptoms and diagnosis (range of four months to six years) for this latter group. Two patients had undergone coccygectomies and one patient a lumbar discectomy prior to establishing the correct diagnosis of sacral chordoma. Seven patients underwent resection and one refused therapy. The four patients who had an initial wide radical resection had a longer disease free survival than the three who underwent local excision. Three of four patients had metastatic disease at the time of death. Early diagnosis and aggressive initial surgical resection are necessary for long-term survival. PMID- 1745048 TI - Effect of prostaglandin E in multiple experimental models. VIII. Effect on host response to metastatic tumor. AB - Prostaglandin E (PGE) is produced by certain tumors and is reported to decrease primary tumor growth. We evaluated its effect in multiple tumor models utilizing a 1 week course of the long acting PGE derivative dimethyl-PGE (dPGE) at a dosage of 100 micrograms/kg/day vs. a lactated Ringers control. For all tumor models, a suspension of 1 x 10(6) colon carcinoma cells were injected into Wistar-Furth rats. When the suspension was injected subcutaneously and the drug was begun at the time of tumor challenge, there was no effect on survival. When the tumor was injected intraperitoneally or intravenously and the drug begun at the time of tumor challenge, dPGE decreased survival time. When the tumor was administered intravenously but dPGE was delayed for 5 days, there was no effect on survival time. When rats were given a 1 week course of dPGE or saline, dPGE was found not to alter natural killer (NK) cell cytotoxicity, macrophage cytotoxicity, spontaneous lymphocyte blastogenesis, or mitogen stimulated blastogenesis. dPGE failed to alter lymphocyte metabolism of glucose in nonstimulated lymphocytes, but decreased the rate of glucose metabolism and adenosine deaminase activity in mitogen stimulated lymphocytes. In conclusion, PGE appears to enhance metastatic growth of tumor lines where it does not alter primary tumor growth. This effect does not appear immunologically mediated. PMID- 1745049 TI - Imaging-guided and nonimaging-guided fine needle aspiration of liver lesions: experience with 406 patients. AB - The aim of the present study was to determine the diagnostic accuracy of different modes of fine needle aspiration (FNA) of liver lesions. A total of 492 FNAs were performed on 406 patients in order to confirm or to rule out focal or multifocal neoplastic disease: 29% under ultrasound (US) guidance, 3% with computed tomographic (CT) guidance, 67% preoperatively, and 1% intraoperatively without imaging guidance. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 387 patients, of whom 264 had malignant liver disease and 123 had benign liver disease. Of 321 aspirations performed in patients with malignant liver disease, the cytologic findings suggested malignancy in 225 (70.1%), suspected malignancy in 25 (7.8%), and did not reveal malignancy in 71 aspirations (22.1%). Among the 123 patients with benign liver disease, the cytologic findings were reported as benign in all but two patients, who had false-positive cytologic findings. The overall sensitivity, specificity, positive, and negative predictive values for cytologic findings were 85.6, 98.4, 99.1, and 76.1%, respectively. The overall diagnostic accuracy was 89.7%. In one patient, fatal intraperitoneal bleeding due to chronic intravascular coagulation complicated the FNA procedure. We conclude that imaging-guided FNA as well as nonguided FNA for cytologic diagnosis of liver lesions are highly accurate and only rarely may be associated with a fatal complication. PMID- 1745050 TI - Combining independently effective anticancer agents may not augment the independent antitumor effects: a study using human digestive organ cancer xenograft lines in nude mice. AB - Five human digestive organ cancer xenograft lines were subcutaneously transplanted in nude mice, and 7 anticancer agents (ACAs) were intravenously administered singly or in combinations at 4 times the standard clinical doses. Cisplatin (P) was effective in 4 lines and 5-fluorouracil (F) was effective in 3 lines. A total of 8 combinations with 2 effective ACAs were assessed in 4 lines and only 1 combination (FP) resulted in an augmented antitumor effect in a single line. A total of 11 combinations with 1 effective ACA plus 1 ineffective ACA were assessed in 2 lines, and only 1 combination (F + carboquone [CQ; Esquinon]) resulted in an augmented effect in a single line. A total of 5 combinations with independently ineffective ACAs were assessed in 1 line, and 1 combination (FP) resulted in augmented antitumor activity. No 2-ACA combinations showed enhanced side effects. Two combinations with 3 effective ACAs were assessed in 2 lines and 1 combination (FP + mitomycin C) resulted in an augmented effect with a greater mortality rate. A total of 12 combinations with both effective plus ineffective ACAs were assessed in 2 lines, and 3 combinations (FP + Adriamycin or FP + CQ or FP + etoposide) resulted in an augmented effect in 1 line with enhanced side effects. These results indicate that the combination of independently effective ACAs does not always cause an augmented antitumor effect, and may sometimes result in augmented side effects. According to this study, the 3-ACA combinations with FP + 1 effective agent appear to be the best regimens for digestive organ cancer. PMID- 1745051 TI - p53 alterations in all stages of breast cancer. AB - Overexpression of the nuclear phosphoprotein p53 is one of the most frequently detected abnormalities in human cancer and appears to be associated with mutation of the p53 gene. In this study of breast cancer, p53 overexpression was detected in two (15%) of 15 pure intraductal tumors, 73 (25%) of 291 primary invasive carcinomas, 13 (50%) of 26 lymph nodes containing metastatic breast cancer, and two of four established breast cancer cell lines. Sequence analysis of selected specimens confirmed that p53 overexpression was associated with mutation of the gene, while no mutations were detected in specimens without p53 overexpression. Thus, overexpression of p53 occurs in all stages of breast cancer and is consistently associated with the production of mutant proteins. Immunohistochemical analysis is a simple method which reliably predicts the presence of most p53 gene mutations in breast cancer specimens. PMID- 1745052 TI - Intermediate lymphocytic lymphoma: its frequency and characteristics in Japan. AB - The nature of intermediate lymphocytic lymphoma (ILL) in Japan was investigated. For this purpose, we have reviewed 1,766 cases of malignant lymphoma and related diseases, and 38 cases were selected as ILL. In two cases, small lymphoid cells proliferated as a wide mantle of atrophic secondary follicles. The frequency of ILL in nodal and extranodal non-Hodgkin's lymphoma was 3.4% and 3.9%, respectively. The frequency was high in orbit and salivary gland lymphomas; two out of three cases and one out of six cases, respectively. Age range (median) and sex ratio (M:F) in nodal and extranodal cases were 34-65 (52) years and 2.1:1 and 22-82 (61) years and 1.1:1, respectively. The majority of nodal ILL presented as systemic disease, but extranodal ILL usually presented as localized disease. ILL when treated with chemotherapy and/or radiotherapy had a favorable prognosis, the 5-year survival rate was 82%. PMID- 1745053 TI - Bilateral renal oncocytomas: management and nuclear analysis. AB - Only 16 cases of bilateral renal oncocytomas have been previously reported in the English language literature, 9 of which were treated with bilateral surgical resections. We report a case treated with bilateral partial nephrectomy. Although pathological examination revealed grade I oncocytomas on both sides, flow cytometry demonstrated tumor DNA content to be aneuploid on one side and diploid on the other, the first cellular differences reported in a case of bilateral renal oncocytomas. The management of suspected renal oncocytomas is discussed, with emphasis on the need for complete excision in most patients. The results of nuclear studies of these tumors, including DNA flow cytometry, cytogenetics, and molecular analysis of both nuclear and mitochondrial DNA, are reviewed. PMID- 1745054 TI - Epidermoid cyst of the testicle in children. AB - Epidermoid cyst of the testicle is rare in children and only four previous cases have been reported. We add two cases and discuss their presentation and management. Both children presented with solid testicular masses, one of which was asymptomatic and the other was painful. Physical examination and ultrasound could not differentiate between a benign and malignant process. One child underwent radical orchiectomy and one child underwent local excision alone. Both are free of disease at follow-up. PMID- 1745055 TI - Carcinoma of the cystic duct. AB - Carcinoma of the cystic duct is a rare neoplasm, and we herein report four cases of carcinoma of the cystic duct. The patients consisted of a 69 year old and 71 year old woman and a 61 year old and 93 year old man. They complained of either abdominal pain or abdominal mass. All the tumors were microscopically well differentiated adenocarcinoma, mostly limited to the wall, that showed no lymph node or distant metastasis. Three patients who had undergone resection were doing well 20 days, 67 months, and 125 months after the operation, respectively. These findings may suggest that not only the early development of symptoms caused by obstruction of the narrow lumen of the cystic duct, but also slow growth and late metastasis produce a favorable clinical course in patients with carcinoma of the cystic duct. PMID- 1745056 TI - Reduction in HLA-DR antigen density on alveolar macrophages of smokers. AB - The expression of HLA class II genes is essential to the antigen-presenting function of monocytes and macrophages. With a new cytofluorometric method of single-cell analysis we investigated the density of HLA-DR antigen expression on alveolar macrophages (AM) of smokers. Although all AM of nonsmokers (100 +/- 1%) expressed HLA-DR antigens, only 79 +/- 12% of AM from smokers showed positive findings (p less than 0.001). Furthermore, the antigen density of those cells expressing this antigen was significantly reduced in smokers (p less than 0.001). The defective expression of class II genes on AM of smokers might contribute to the impaired antigen-presenting function found by some previous investigators. PMID- 1745057 TI - Lung reflexes and receptor activity in a rabbit model of pulmonary fibrosis. AB - Our objective was to see if activity of individual slowly and rapidly adapting pulmonary receptors was changed by pulmonary fibrosis. Diffuse interstitial lung fibrosis of several weeks' standing was induced in 8 rabbits. They displayed changes in lung mechanics and patterns of breathing, when compared to control rabbits, similar to those seen in patients who develop pulmonary fibrosis. Lung reflexes in the fibrotic rabbits were more profoundly changed than eupneic breathing in a way that could be interpreted as slowly adapting receptor activity, which was increased, being overpowered by a prepotent input from pulmonary rapidly adapting receptors. An increase in number of active rapidly adapting receptors was found in the fibrotic rabbits during direct vagal recording. We have demonstrated that pulmonary receptor activity is changed by lung fibrosis. It may be that these changes in receptor activity produce conflicting respiratory drives that could result in the sensation of dyspnea. PMID- 1745059 TI - Percutaneous transthoracic needle biopsies in the rapid diagnosis of pulmonary tuberculosis. AB - From May, 1987, to December, 1990, 173 percutaneous transthoracic needle biopsies (PTNB) using a 19-gauge spinal needle under uniplane fluoroscopic guidance were performed in 160 patients. Thirty-one patients had a final diagnosis of pulmonary tuberculosis. These patients with tuberculosis underwent a total of 35 biopsies. Twenty of 35 (57%) had definite histologic features of tuberculosis with stainable acid-fast bacilli, 4/35 (11.5%) had granulomatous or caseous lesion consistent with tuberculosis, and 11/35 had nonspecific inflammatory changes. When results were matched with the sputum culture results, 15/35 specimens (43%) provided the exclusive means of diagnosis of tuberculosis. Five of 35 (14%) patients developed postbiopsy pneumothoraces. The overall acceptance by patients was good. This report indicates the potential usefulness of PTNB in the rapid diagnosis of selected cases of suspected pulmonary tuberculosis. The yield was comparable to fiberoptic bronchoscopy, currently commonly used in the diagnosis of pulmonary mycobacterial disease. The procedure was noted for its simplicity. PMID- 1745058 TI - Lactoferrin and secretory IgA in the bronchoalveolar lavage fluid from patients with a stable asthma. AB - We have measured lactoferrin and secretory IgA (sIgA) in the unconcentrated bronchoalveolar lavage fluid (BALF) from nonsmoking healthy volunteers (n = 10) and nonsmoking patients with stable asthma (n = 14). The median concentrations and the ranges of lactoferrin were controls, 0.13 mg/L (0.01-0.43 mg/L); asthma, 0.41 mg/L (0.07-7.51 mg/L). For sIgA the results were controls, 0.48 mg/L (0.12 1.47 mg/L); asthma, 1.29 mg/L (0.65-14.6 mg/L). The concentrations in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. SIgA and lactoferrin levels in the BALF and ELF from the patients with asthma were higher than in controls (Mann-Whitney U-test, p less than 0.03). Our results indicate that in patients with stable asthma the airway epithelial cells are activated, resulting in an enhanced secretion of lactoferrin and enhanced secretory transport of sIgA into the airway lumen. PMID- 1745060 TI - Immune parameters in a population of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations. AB - Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence. PMID- 1745061 TI - Impairment of lymphocyte activities in depressed aged subjects. AB - Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence. PMID- 1745062 TI - Calcium 'homeostatic' effect of 1 alpha,25-dihydroxycholecalciferol on young adult mouse calvaria in organ culture. AB - The effect of 1 alpha,25-dihydroxycholecalciferol on calcium release from cultured young adult (75-day-old) mouse calvaria in the presence of indomethacin or dexamethasone was studied. Indomethacin (2.8 x 10(-7) M) or dexamethasone (10( 8) M) abolished or considerably inhibited basal calcium release. At 2.6 x 10(-7) M, 1 alpha,25-dihydroxycholecalciferol prevented the effect of either indomethacin or dexamethasone, resulting in higher calcium release levels approximating those observed in cultures containing only 1 alpha,25 dihydroxycholecalciferol. We have shown previously that in contrast to its effect on neonatal mouse calvaria in culture, 1 alpha,dihydroxycholecalciferol either failed to enhance or even inhibited basal calcium release from cultured 75-day old mouse calvaria. Furthermore, 1 alpha,25-dihydroxycholecalciferol inhibited PTH- or PGE2-enhanced calcium release from such cultures. These studies demonstrated that, at the same concentration, 1 alpha,25-dihydroxycholecalciferol decreases high calcium release due to various bone resorption-stimulating factors and increases low calcium release values due to various bone resorption inhibiting factors. This suggested that this vitamin D3 metabolite directly regulates the degree of bone resorption at the bone tissue level resulting in a local calcium 'homeostasis'. PMID- 1745063 TI - No relationship between the age-related decrease in prostacyclin production and the level of intracellular lipid peroxidation in human umbilical vein endothelial cells in culture. AB - Some investigators have speculated that a decrease in prostacyclin production observed during ageing of endothelial cells is caused by an increase in intracellular lipid peroxide. We checked this speculation using an in vitro model to study the ageing of human vascular endothelial cells. For this purpose we determined the levels of intracellular lipid peroxide of endothelial cells at various culture ages, and found that the level of intracellular lipid peroxidation did not increase during in vitro ageing. Amounts of intracellular lipid peroxide also differed depending on the growth phase, the addition of heparin and the strain of endothelial cells, but the cells producing prostacyclin at a low level did not necessarily contain larger amounts of intracellular lipid peroxide. Therefore, we postulate that the age-related decrease in prostacyclin production is not due to an increase in the amount of intracellular lipid peroxide as a function of age. PMID- 1745064 TI - Muscle fiber branching--difference between grafts in old and young rats. AB - Large numbers of branched muscle fibers occur in the freely grafted rat extensor digitorum longus muscle. The ratio of branched/non-branched muscle fibers in grafts is much higher in old (24 months) than in young (4 months) host rats. Cross-age transplants show that the proportion of branched muscle fibers is related to the age of the grafted muscle and not to the age of the host. This is in contrast to mass and maximum isometric tension, in which the age of the host, rather than the age of the grafted muscle, is the determinant of the success of the muscle graft. PMID- 1745065 TI - Effect of aging and other factors on monocyte aryl hydrocarbon hydroxylase activity. AB - A measure of the activity of macrophage drug metabolizing enzymes through assay of peripheral monocytes was used to assess the hepatic enzymatic status and thereby evaluate age related changes in drug metabolism. Blood was obtained from elderly subjects (aged 74.8 +/- 5.2, mean +/- S.E., n = 16) and a young control group (aged 23.5 +/- 2.0, n = 27). Monocyte AHH activity was used as an index of liver drug metabolism, ALT activity as an index of liver function, monocyte media IL-1 and as an index of macrophage activation and serum IL-1 levels as a measure of endogenous pyrogenic activity. The medium collected from the cultured monocytes was also assessed for the presence of AHH inhibitory activity. Subjects provided information relating to their age, sex, alcohol consumption, cigarette smoking, recent infection, recent surgery, disease status and medications which could alter drug metabolism. Elderly patients were drawn both from independent seniors living at home and seniors visiting a geriatric day hospital and compared to a control group of young healthy volunteers. Using the experimental design AHH activity did not differ within experimental error between aged (0.832 +/- 0.32 nmol/mg prot. per h, n = 16) and young control subjects (0.452 +/- 0.17, n = 27). ALT activity did not differ between aged (2.83 I.U. +/- 0.46) and young (4.24 +/- 0.82). Monocyte AHH activity did not differ between males (0.45 +/- 0.14, n = 33) compared to females (0.65 +/- 0.18, n = 29), but was significantly higher in smokers (2.5 +/- 1.0, n = 5) compared to non-smokers (0.35 +/- 0.05, n = 52). Mild to moderate alcohol use showed no significant effect on AHH activity. There was no significant difference between the mean level of MCM inhibition of murine hepatocyte AHH between elderly (44.3 +/- 8.32%, n = 8) and control (31.5 +/- 6.21%, n = 15) subjects, but a larger proportion of the elderly population demonstrated such an effect. Serum IL-1 levels (range 0-55.9 pg/ml) were compared to MCM IL-1 and AHH inhibitory activity in the elderly and young group. PMID- 1745066 TI - Hepatic drug metabolism during development in food-restricted female Sprague Dawley rats. AB - Hepatic drug metabolism was investigated in female Sprague-Dawley rats fed ad libitum (A) or a restricted diet (R) (implemented from age 1 month), at 1.5, 4.5 and 12 months to determine the short- and long-term effects of caloric restriction. Microsomal cytochrome P-450 content and NADPH cytochrome c reductase activity were not modified by age. While dietary restriction did not affect cytochrome P-450, it significantly increased NADPH cytochrome c reductase activity at all time periods when compared to corresponding A-fed groups. Aniline hydroxylase and aminopyrine N-demethylase activity tended to decrease with age in the A-fed groups but the differences did not prove to be statistically significant. A significant decrease of aminopyrine N-demethylase was observed with age in R rats. A significant reduction of aniline hydroxylase activity was noted in the R groups compared to age-matched A-fed controls. In contrast, aminopyrine N-demethylase activity increased significantly, but only at 1.5 months of age. Glutathione S-transferase activity was augmented between 1.5 and 4.5 months of age, and this was followed by a significant decrease at age 12 months in both A and R groups. Dietary restriction had no effect on this enzymatic activity. The microsomal cholesterol and phospholipid content as well as the cholesterol/phospholipid molar ratio changed significantly between 1.5 and 4.5 months of age but not between 4.5 and 12 months of age. These parameters were unaltered by dietary restriction. In conclusion, in the female Sprague-Dawley rat there are no statistically significant changes in hepatic microsomal components and drug metabolizing capacity between 1.5 and 12 months of age. Dietary restriction resulted in significant changes in enzymes related to drug metabolism which varied with the enzyme examined. In general, these changes were similar after short- or long-term dietary intervention. PMID- 1745067 TI - Growth retardation in senescent arterial smooth muscle cells and its reversal following brain stimulation: implications for atherogenesis. AB - Advancing age and psychosocial stress are each associated with a rising incidence of atherosclerosis. In this investigation we attempted to answer the question of whether they are independent of each other or not. Since a key feature of atherosclerosis is the proliferation of arterial smooth muscle cells (ASMC), we transplanted aortic tissue from aged rats, half of which had received hypothalamic stimulation, as a model for stress, to growth supporting medium, immediately after stimulation and observed their growth behavior for a period of 4 months. Similar observations were carried out on young animals for comparison. Although there was little difference in outgrowth frequency of explants from young animals between stimulated and non-stimulated subjects, in the case of the older rats, explants from animals which were not stimulated were considerably retarded in their growth, whereas those from subjects which had received HS, grew as well as those of the younger ones. These results show that HS can reverse the growth decline in aortic tissues explanted from senescent rats. They also suggest that age per se is not atherogenic in terms of proliferative behavior of ASMC, whereas when interacted with a stressful condition, this may be the case. Since in the elderly there is a decreased tolerance to stress, the 'atherogenic' effects of age in these individuals may be mediated through the stress response. PMID- 1745068 TI - Mathematical modeling for the aging process: normal, abnormal and self terminating phenomena in spatio-temporal organization. AB - An elucidation of the aging process is attempted using a simple one-dimensional multicellular system, a prototype of living organisms. This model analysis has the advantage of making us investigate the two types of modes of their dynamical behavior: (i) the local modes of behavior of individual cells and (ii) the global modes of behavior of the total system. At first, each cell is assumed to have biochemically excitable kinetics for local modes, and then what kind of the global modes results with change in intercellular interaction is examined. With a simple interaction as possibly occurs in the early stage of differentiation, the model displays well-coordinated spatio-temporal patterns. This may be interpreted as a normal state. With a more complex interaction as possibly occurs in the late stage of growth, however, the model produces much more erratic patterns. This may refer to an abnormal state. Interestingly, these abnormal patterns can be transformed into normal patterns, when the activity of some parts of this model is turned 'off'; the system can survive at the sacrifice of its parts. This makes us imagine that programmed cell death plays an important role in development during morphogenesis. When individual cells become less sensitive to intercellular signals and still possess intrinsic excitability, then the normal patterns are developed for a short while before being replaced by rather irregular patterns. As time proceeds, however, all activity of them disappears. We call this a 'self-terminating' phenomenon, which may refer to aging. This strongly suggests that the loss of the total system function, leading to death, results from a global mode of system failure but not from a local mode of subsystem failure. PMID- 1745069 TI - Age-associated changes in neuroaxonal transport in the hypothalamo neurohypophysial system of the mouse. AB - In this study, we investigated age-associated changes in neuroaxonal transport of the hormone vasopressin (AVP) and its associated neurophysin (NPII), from the supraoptic nucleus (SON) of the hypothalamus to the neurohypophysis. C57BL/Icrfat male mice of 6 and 28 months of age were injected in the hypothalamus with L [35S]cysteine. Animals were killed up to 2.25 h after injection and NPII and AVP from the SON and neurohypophysis were separated using HPLC, and the fractions counted for radioactivity. In the SON, radiolabelled NPII and AVP were first detected after 0.50 h in both young and old mice. There was no significant difference between the age-groups in the incorporation of radiolabel over the time course studied. Radiolabelled NPII in the neurohypophysis was significantly above background after 1.25 h in the young, and after 1.50 h in the old mice. The differences between the two age groups was significant (P = 0.05). Radiolabelled AVP followed a similar trend, but was not significantly above background until 1.50 h in the young and 1.75 h in the old. The differences between the two age groups was on the point of significance (P = 0.056). These results indicate a significant reduction of up to 25% in the rate of axonal transport of neurohypophyseal peptides with advancing age. PMID- 1745070 TI - Longitudinal Gompertzian analysis of breast cancer mortality in the U.S., 1962 1987: demonstration of a disorder displaying complex deterministic mortality dynamics. AB - Age-adjusted mortality rates for breast cancer (BC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted BC mortality rate distributions for women display two distinct Gompertzian slopes. Between age 15 and 40 years, age-adjusted BC mortality rate distributions intercepted at age 33.5 years and mortality rate (per 100,000) 5.83. Between age 50 and 85 years, age-adjusted BC mortality rate distributions intercepted at age 60.4 years and mortality rate 77.0. These two distinct Gompertzian regions correspond to the clinical and biological classification of BC into pre- and post menopausal varieties. The observation that postmenopausal BC increases in environments conducive to survival and that premenopausal BC increases in environments that are less favorable becomes understandable when BC mortality dynamics are viewed from a competitive and deterministic perspective. PMID- 1745071 TI - Age-related differences in promoter-induced extension of in vitro proliferative life span of Syrian hamster fibroblasts. AB - The proliferative capacity of Syrian hamster dermal fibroblasts has been previously shown to be inversely related to the age of the donor (Mech. Ageing and Dev., 34 (1986) 151). The present study demonstrates an inverse correlation between in vivo age and the in vitro morphological and proliferative response of Syrian hamster dermal fibroblasts to the tumor promoter phorbol-12,13 didecanoate. Treatment of fetal fibroblasts with promoter increased the proliferative life span of the cultures by approximately 2-fold, but did not increase the frequency of conversion to established cell lines. Neonatal and young adult fibroblasts exhibited intermediate responses to promoter treatment, showing 54.9% and 33.1% extension, respectively. In contrast, promoter treatment had no significant effect on aged adult fibroblasts. Maximal extension required continual treatment beginning in primary culture or at passage 1. Promoter induced extension of proliferative life span appears to be mediated through the prolonged maintenance of small, highly proliferative cells that are present in primary cultures of these cells. PMID- 1745072 TI - A study on the basic nature of human biological aging processes based upon a hierarchical factor solution of the age-related physiological variables. AB - The purpose of this study is to determine the laws governing the aging processes based on a hierarchical factor solution of the age-related physiological variables. Healthy individuals (462) who had taken a 2-day health examination were studied. Twenty-seven physiological variables were submitted to hierarchical factor solution. The analysis revealed that there was a fixed pattern in the variations of these 27 physiological variables. In this hierarchical factor solution, three group factors as functioning at different levels of complexity composed of the 16 common factors were extracted. Of these group factors, the first and third group factors can be referred to the aging process. The first group factor, the so-called factor 1 loaded with most of physiological variables, was interpreted as a primary aging factor which presented the primary process of human aging. The third group factor, the so-called factor 6 to 16 loaded only with a few variables related to a single physiological system or organ, were interpreted as system-specific secondary aging factor. These results obtained by the hierarchical factor solution thus seem to support the notion that biological age changes can be viewed as time dependent complex integration of the primary and secondary aging processes. PMID- 1745073 TI - Comparison of rates of neuronal development and survival in human and rat cerebral cortical cell cultures. AB - A problem that has not been addressed directly at the cellular and molecular levels concerns the basic mechanisms governing rates of development and aging in the nervous system. We have begun to examine this problem by employing parallel cell cultures of cerebral cortical neurons taken from rat and man, two species with markedly different developmental periods and life spans. Cortical cultures were established from rat and human fetuses and were maintained under identical conditions. Long-term neuronal survival in human cortical cultures was strikingly greater than in rat cortical cultures, and axonal outgrowth was significantly slower in the human neurons. These differences were consistently observed in a variety of culture media. Exchanges of culture medium between cultures of the two species did not alter the differences in neuronal survival and axon outgrowth suggesting that the differences between human and rat neurons were probably not due to factors released into the culture medium. Furthermore, the differences were not related to developmental stage at the time of culture initiation since similar results were obtained in cultures established from fetuses of different gestational ages. These initial data indicate that differences in the developmental time courses and life spans of human and rat cerebral cortex are reflected at the level of the individual neuron, and provide a system in which to explore the mechanisms responsible for these differences. PMID- 1745074 TI - Hydrogen peroxide production by mitochondria may be a biomarker of aging. AB - The hypothesis that rate of intracellular prooxidant production is associated with the rate of aging was tested by comparing the rate of H2O2 generation by mitochondria in houseflies of similar chronological but different physiological ages. Physiological age represents the life expectancy or 'nearness to death'. Average and maximum life spans of flies were extended 2-fold by the elimination of flying activity. In addition, using senescence-related loss of flight ability as a phenotypic marker of impending death, relatively short-lived and long-lived subpopulations of flies were isolated from cohort populations. Rate of H2O2 generation was measured fluorometrically in mitochondria from thoracic flight muscles using alpha-glycerophosphate as a substrate and without employing any respiratory inhibitors as is often the case in mammalian studies. The rate of mitochondrial H2O2 release was found to be associated with life expectancy or the physiological age of flies rather than the chronological age. At the same chronological age, mitochondria from flies with a shorter life expectancy had a markedly higher rate of H2O2 generation than those with a longer life expectancy. Results of this and some previous studies in this laboratory are interpreted to suggest that the rate of prooxidant generation rather than the level of antioxidant defenses may be a key correlate of the rate of aging. PMID- 1745075 TI - Skeletal muscle atrophy in old rats: differential changes in the three fiber types. AB - This study was undertaken to reevaluate the effects of ageing on skeletal muscle mass and on mitochondrial and glycolytic enzyme levels in the different types of skeletal muscle in rats. It was found that some muscles atrophy with ageing, while others do not, in male rats. Atrophy appears to occur in weight-bearing muscles, and is most marked in those with a high proportion of type IIb fibers. The muscles that did not atrophy are non-weight-bearing, and include the epitrochlearis (predominantly type IIb fibers) and the adductor longus (predominantly type I fibers). The average cross-sectional area of muscle fibers in the plantaris muscles of 28-30-month-old rats was approximately 30% smaller than that of 9-10-month-old animals, providing evidence that the approximately 30% lower weight of the plantaris in the old group was entirely due to fiber atrophy. The proportion of type IIa fibers was decreased and the proportion of type I fibers was increased in the plantaris of the old rats. The respiratory capacity of the soleus muscle (predominantly type I fibers), and the glycolytic capacity of the superficial, white (type IIb) and deep, red (predominantly type IIa) portions of the vastus lateralis, were reduced in the old rats. Our results provide evidence that ageing has differential effects on the three types of skeletal muscle fiber, and on weight-bearing and non-weight-bearing muscles, in the rat. PMID- 1745076 TI - The structure of self-reported physical health among the aged in the United States and Japan. AB - This article attempts to extend the generalizability of a three-dimensional model of self-reported physical health among the aged to a nonwestern culture. Consisting of three interrelated dimensions, chronic illness, functional status, and self-rated health, this model was empirically evaluated by using national data on the aged gathered in the United States and Japan. The three-dimensional specification was found to apply equally well to U.S. and Japanese elderly. In addition to examining the internal structure of this three-dimensional model, the study assessed the model's relationships with a set of selected exogenous variables including age, sex, marital status, and education. The relationships between the selected exogenous variables and physical health dimensions are largely similar in both countries. However, clear differences appeared in at least three instances. PMID- 1745077 TI - Economic determinants of annual hours worked by registered nurses. AB - This study was guided by the economic theory of the decision to work, with secondary survey data (N = 16,880) derived from the National Sample Survey of the Population of Registered Nurses, November 1984, used to analyze the effects of economic and sociodemographic variables on the number of hours worked annually by registered nurses (RNs). When separate analyses were performed for the entire sample and for unmarried RNs alone, regression coefficients estimated for the RN's wage indicated that raising wages would result in modest increases in the number of annual hours worked. This effect was not present when either married RNs or those who were widowed, divorced, or separated were used in regression analyses. Male RNs worked 11 weeks more than married, female RNs, and nonwhite RNs worked almost 7 weeks more per year than white, married RNs. RNs with an associate degree in nursing worked more hours than those with a diploma certificate, and the presence of young children at home had a substantial negative effect on the number of hours RNs worked. PMID- 1745078 TI - A time-insensitive predictive instrument for acute myocardial infarction mortality: a multicenter study. AB - This study develops a "time-insensitive" predictive instrument for acute myocardial infarction mortality that would be useful both as a real-time clinical decision aid in the emergency medical setting and also for retrospective assessment and comparison of medical care based on risk-adjusted mortality predictions. This was done using prospectively-collected data on 5,773 patients with chief complaints of chest pain or other symptoms suggesting acute cardiac ischemia who came to six New England hospitals over a 2-year period. In phase one, based upon 4,099 patients, multivariate logistic regression was used to develop the predictive instrument. In phase two, its accuracy and diagnostic performance were tested on an independent sample of 1,387 patients presenting with symptoms compatible with acute cardiac ischemia. Discrimination between patients who lived and those who died was reflected by receiver-operating characteristic (ROC) curve areas of 0.85, 0.80, and 0.76, respectively, for all emergency department study subjects regardless of final diagnosis, subjects who proved to be having acute cardiac ischemia, and subjects who proved to be having acute infarction. Good calibration was shown by the fact that the predicted mortality was found to not vary significantly from actual mortality rates across deciles of predicted probabilities from 0% to 100%. In phase three, based on all 945 study subjects with acute myocardial infarction, each of the six hospitals' actual mortality rates were compared to their rates predicted by the predictive instrument. Actual hospital mortality rates ranged from 9.9% to 19.3%, with one hospital having a significantly higher rate (P = 0.005) and two hospitals both). Predicted mortality rates ranged from 13.4% to 19.4%, with one hospital having a significantly higher predicted rate (P = 0.005) and two hospitals having significantly lower predicted rates (P = 0.04 and P = 0.03). Individual hospitals' differences between actual and predicted mortality ranged from -3.4% to +3.1% (all NS). When grouped by hospital type, the actual mortality rates were 14.9%, 17.3%, and 13.0%, respectively, for urban teaching, smaller city teaching, and rural nonteaching hospitals (all NS). The predicted mortality rates were 16.5%, 17.1%, and 13.6%, respectively, with the rate for rural nonteaching hospitals being significantly lower (P = 0.009). No hospital type had significant differences between their actual and predicted mortality rates (NS). The time insensitive predictive instrument for acute infarction mortality shows potential for risk-adjusted studies of hospitals mortality for multihospital groups, hospital-to-hospital comparisons, and within-hospital assessment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745079 TI - Controlling variation in health care: a consultation from Walter Shewhart. AB - The control of unintended variation is an objective central to modern industrial quality management methods, based largely on the theoretical work of Walter A. Shewhart. As industrial quality management techniques find their place in health care, professionals may feel threatened by the effort to reduce variation. Understanding may reduce this fear. Variation of the types addressed in quality control efforts erodes quality and reliability, and adds unnecessarily to costs. Such undesirable variation derives, for example, from misinterpretation of random noise in clinical data, from unreliability in the performance of clinical and support systems intended to support care, from habitual differences in practice style that are not grounded in knowledge or reason, and from the failure to integrate care across the boundaries of components of the health care system. Quality management efforts can successfully reduce each of these forms of variation without insult to the professional autonomy, dignity, or purpose of health care professionals. Professionals need to embrace the scientific control of variation in the service of their patients and themselves. PMID- 1745080 TI - Accuracy of Medicare claims data for estimation of cancer incidence and resection rates among elderly Americans. AB - To explore the reliability of Medicare Part A claims data for clinical and health services research related to the care of patients with cancer, the authors compared estimates of the incidence of and resection rates for cancer of the breast, colon, and lung derived from analysis of Medicare Part A data versus data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Incidence rates of breast, colon, and lung cancer estimated from Medicare Part A data were within 6% of estimates derived from SEER data. Resection rates estimated from Medicare Part A data, in contrast, were 12% to 27% lower than resection rates based on SEER data. This discrepancy is not explained by variations in practice between regions participating in versus those not participating in the SEER registries but may be due to undercoding of surgical procedures in Medicare Part A data. This analysis suggests that Medicare data can provide useful insights into the care of patients with cancer, but research regarding inpatient procedures employed in management of cancer should be based on analysis of Medicare Parts A and B data combined. PMID- 1745081 TI - Variation in intensive care unit practices in two community hospitals. PMID- 1745082 TI - Willingness-to-pay as a measure of benefits. Relevant questions in the context of public decisionmaking about health care programs. PMID- 1745083 TI - [Concentrations of serum cholesterol in Spanish children: results of a study on the isle of Menorca]. AB - BACKGROUND: The little knowledge about the distribution of total cholesterol (TC) in childhood and adolescence in Spain, makes the planification of preventive measures for cardiovascular diseases difficult. The aim of this study is to determinate these values in the island of Menorca. METHODS: A sample of 1,062 boys and girls 6 to 18 years of age was studied. Blood samples were obtained by venipuncture and were analyzed by the enzymatic techniques of cholesterol esterase, cholesterol-oxidase, and peroxidase. RESULTS: Boys showed lower mean TC values than girls in almost all age groups. In both sexes, a descending phase was observed in the TC by age curve at the beginning of the adolescence. TC values above 5.17 mmol/l (200 mg/dl) were recorded for 7% of participants, being this proportion lower than the value found in the Spanish study of Fuenlabrada (13%). CONCLUSIONS: Results obtained are compared with other national and international studies. The values of this study rank an intermediate position between the highest mean TC values registered in Norway and the lowest registered in Israel. PMID- 1745084 TI - [Multiple nosocomial infections in a university hospital]. AB - BACKGROUND: Multiple hospital-acquired infections (MHAI) have not been properly evaluated, and therefore data on their leading epidemiological features are lacking. In the present study, MHAI in a university hospital were evaluated during a 5 year period. METHODS: Data were obtained from the institution program of hospital acquired infection surveillance, which is based on the daily review of microbiological reports with subsequent confirmation of the data in the service where the patient is admitted. RESULTS: The number of detected MHAI was 1,202 in 522 infected patients, corresponding to 10.3% of the overall number of patients with hospital-acquired infections (HAI). By age groups, the patients over 60 years were the most affected (62.7%), whereas the less affected were those below 40 years (13.6%). By hospital areas, the surgical area had the highest incidence (55.3%) and the gynecological area had the lowest incidence (2.4%). Double infections were the most common ones in all services, with 79.1% of the overall number. The service with the greatest number of patients with MHAI was Surgery (37.9%). Urinary tract infections were the most common type. CONCLUSIONS: The results show that male surgical patients over 60 years of age were the group at highest risk of MHAI. PMID- 1745085 TI - [Clinico-hematological characteristics of acute transformation of chronic myeloproliferative syndromes]. AB - BACKGROUND: The aim of the present study was to analyze the blastic transformation occurring during chronic myeloproliferative diseases (CMPD) and to establish the differences between them. METHODS: The clinical and hematological characteristics of 54 patients in blastic crisis (BC) of a CMPD were analyzed: 40 chronic myelogenous leukemias (CML), 9 idiopathic myelofibroses (IMF), 4 polycythemia vera (PV), and one essential thrombocythemia (ET). The results were analyzed by the BMDP statistical program. RESULTS: The BC of CML appeared in younger patients (p less than 0.05). Only in this group did some patients achieve complete remission. Moreover, in this BC a greater incidence of visceromegalies and leukocytoses were observed. The BC of the IMF patients led to marked anemia (p less than 0.01) and bone marrow infiltration (p less than 0.05); these leukemias were more frequent in males and began with lymphadenopathies and visceromegalies. The transformations of PV were preceded by a longer chronic phase and had a lower incidence of visceromegalies and a nearly normal hemoglobin count value. The patient with acute leukemia secondary to ET did not display visceromegalies but did have anemia, leukopenia and a normal platelet count. None of the four groups responded to therapy, and their survival was short. CONCLUSIONS: Blast transformations of different myeloproliferative disorders have their own idiosynchratic clinical and hematological characteristics, some of these may be related to the chronic phase of disease. PMID- 1745086 TI - [Cholesterol in Spanish children and adolescents. Uncertain outlook for the future cardiovascular risk of the population]. PMID- 1745087 TI - [Rheumatoid arthritis and multiple neoplasms]. AB - In patients with rheumatoid arthritis the appearance of neoplastic disease has been fundamentally described of lymphoproliferative origin. The case of a 59 year old woman with rheumatoid arthritis of a 4 year evolution is reported. The patient was treated with gold salts and methotrexate and presented successively a bronchogenic carcinoma and a non-Hodgkin lymphoma. The epidemiologic studies in the relation of rheumatoid arthritis-neoplasia are discussed and the pathogenic hypotheses to the immune alterations as well as the treatments employed are described. PMID- 1745088 TI - [Prevention of azoospermia in patients treated with chemotherapy and/or radiotherapy]. PMID- 1745089 TI - [Liver transplantation]. PMID- 1745090 TI - [Recurrent acute streptococcal thyroiditis]. PMID- 1745091 TI - [Pulmonary scintigraphy with gallium-67 in the early detection of Pneumocystis carinii pneumonia]. PMID- 1745092 TI - [Hypercoagulability and exanthematous Mediterranean fever]. PMID- 1745093 TI - [Soft tissue sarcoma]. PMID- 1745094 TI - [Randomly]. PMID- 1745095 TI - [Glycated hemoglobin, glycosylated hemoglobin or glycohemoglobin? A problem of biochemical nomenclature]. PMID- 1745096 TI - [Infectious arthritis in hemophiliac patients with positive antibodies to human immunodeficiency virus. Apropos of 4 cases]. PMID- 1745097 TI - [Incidence of seroconversion for the human immunodeficiency virus in non hemophiliac patients receiving low doses of prothrombin complex factors]. PMID- 1745098 TI - [Complicated parapneumonic pleural effusion resolved with antibiotic treatment]. PMID- 1745099 TI - [Prevention of traffic accidents by physician's consultation]. PMID- 1745100 TI - Losartan, a nonpeptide angiotensin II (Ang II) receptor antagonist, inhibits neointima formation following balloon injury to rat carotid arteries. AB - Angiotensin-converting enzyme inhibitors have been shown to inhibit intimal thickening following balloon catheterization of rat carotid arteries. To assess the role of the renin-angiotensin pathway and the angiotensin type-I (AT1) receptor in this effect, the nonpeptide Ang II antagonist losartan (DuP 753) or vehicle was infused continuously i.v. in rats from two days before to two weeks after balloon injury to the left common carotid artery; drug effects upon intimal thickening were examined histologically. Losartan produced a dose-dependent reduction in cross-sectional area of intimal lesions determined two weeks post balloon injury. At 5 mg/kg/day a nonsignificant 23% reduction of intimal area was observed. At the higher dose of 15 mg/kg/day, losartan produced a 48% reduction in intimal area (P less than 0.05) compared to the vehicle-infused group. The cellular density of the neointima was not affected by losartan, indicating a probable effect of the drug upon migration and/or proliferation of smooth muscle cells. In separate groups of non-ballooned rats, losartan infusions of 5 and 15 mg/kg/day produced significant rightward shifts (averaging 6.4- and 55-fold, respectively) in curves relating increases in blood pressure to intravenous Ang II in pithed rats determined between 2 and 16 days following initiation of losartan infusion. Mean arterial blood pressure (determined under alpha chloralose anesthesia) was reduced following continuous losartan infusion for 6 days from 128 +/- 8 mm Hg (vehicle) to 105 +/- 8 mm Hg at 5 mg/kg/day (P less than 0.05), and 106 +/- 4 mm Hg at 15 mg/kg/day (P less than 0.05). Thus, losartan attenuated the vascular response to balloon catheter injury, and this effect was associated with functional block of vascular AT1 receptors. The results support a role for Ang II, acting via AT1 receptors, in myointimal thickening subsequent to balloon injury of rat carotid arteries. PMID- 1745101 TI - Minireview: enzymatic properties of ribosome-inactivating proteins (RIPs) and related toxins. AB - Ribosome-inactivating proteins (RIPs) are a group of proteins that inhibit protein synthesis in eucaryotic cells. While the biological effects have been well characterized, the underlying enzymatic mechanisms have not been elucidated until recently. Two different mechanisms have been identified. Plant and bacterial RIPs act as N-glycosidases. They cleave a single N-glycosidic bond between adenine and ribose at a specific nucleotide A-4324 of the 28S rRNA of the 60S ribosomal subunit. On the other hand, the fungal RIPs act as ribonucleases and cleave a single phosphodiester bond between G-4325 and A-4326 of the same rRNA, just one nucleotide away from the site of action of plant/bacterial RIPs. Other protein synthesis inhibitory proteins act by their ADP-ribosyltransferase activity which modify and thus inactivate elongation factor-2. Recently, some toxins have been shown to possess deoxyribonuclease activity which may also account for their toxicity. PMID- 1745102 TI - Ion-sparing diuresis by 2,3-dibenzylbutane-1,4-diol, a synthetic mammalian-lignan derivative. AB - Diuretic properties of a synthetic lignan, 2,3-dibenzylbutane-1,4-diol (hattalin), and a naturally occurring arctigenin were examined in BALB/c male mice and Wistar male rats. Intra peritoneal administration of hattalin (50 mg/kg) in mice increased urine volume by 1.7-3.1 fold that of placebo-treated animals 40 260 min after administration (p less than 0.05 vs control). In contrast, 100 mg/kg of arctigenin had no effect on urine volume in mice. Hattalin (100 mg/kg), arctigenin (100 mg/kg), or furosemide (50 mg/kg) as a positive control was administered orally to rats, and accumulated urine volume was measured for up to 6-12 h. The urine volume of animals administered with hattalin showed 1.4-1.5 fold that of placebo-treated animals after 2-6 h of administration (P less than 0.05, n = 10). On the other hand, arctigenin showed no significant effect on urine volume for up to 12 h after administration (n = 8). The urine volume in animals administered with furosemide (n = 10) was 2.0-3.0 fold that of placebo treated animals (P less than 0.01). Furosemide increased total Na+, K+, or Cl- excretion by 1.9, 1.8 or 2.2 fold, respectively, when compared with placebo treated controls (P less than 0.01), whereas hattalin decreased Na+ excretion by 3.6 times (P less than 0.01), K+ excretion by 1.4 times (not significant), and Cl excretion by 3.1 times (P less than 0.01). Serum Na+ and K+ levels did not change in both furosemide- and hattalin-administered rats, however, serum Cl- levels in these animals significantly decreased (P less than 0.01) when compared with controls. The results suggest that the diuretic property of hattalin is due to a novel mechanism which is different from that of furosemide or other diuretics modifying the ion-exchange at the uriniferous tubules. PMID- 1745103 TI - Enzymatic degradation of tumor necrosis factor by activated human neutrophils: role of elastase. AB - Although the role of tumor necrosis factor-alpha (TNF) as mediator of inflammation is now well established, its interactions with polymorphonuclear neutrophils (PMN) are not fully understood. Therefore, we investigated the possible hydrolytic action on TNF of intra-lysosomal enzymes released by activated PMN in the extracellular medium. We first incubated 125I radiolabeled TNF in vitro with activated PMN and by HPLC analysis, we observed a degradation process completely blocked by the previous addition of alpha 1-Antitrypsin (AT) to the incubation medium. By comparing several degradative patterns of TNF obtained with purified leukocyte proteases and supernatant of activated PMN, we identified elastase as the major enzyme involved in this catabolic process of TNF. In a second part, we determined the bioactivity of the cleavage fragments of recombinant human TNF (rhTNF) by a cytotoxicity assay. None of the fragments was found biologically active. Our results suggest that, at inflammatory sites, an enzymatic degradation of TNF may occur in the pericellular area of activated PMN. This new catabolic pathway leading to inactivation of TNF might be regarded as an effective local negative feed-back process limiting the potentially toxic effects of this cytokine. PMID- 1745104 TI - Antagonism of acute cocaine toxicity by buprenorphine. AB - The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ("speed ball") toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs. PMID- 1745105 TI - A novel and sensitive radioreceptor assay for serum melatonin levels. AB - A simple and sensitive radioreceptor assay (RRA) has been developed to measure melatonin levels in serum. The assay is based on competition between 2 [125I]iodomelatonin ([125I]MEL) and melatonin for binding to high-affinity binding sites in chick forebrain. To measure the amount of melatonin present in a serum sample, it was extracted with dichloromethane and added to the assay medium. The percentage inhibition of radioligand binding in the presence of the extracted serum was determined and compared to the percent displacement by known amounts of melatonin in a standard curve. There was little or no cross-reactivity with other structurally related compounds. The sensitivity of the assay is approximately 1.5pg/0.15 mL and the intra- and inter-assay variations are approximately 8%. Since the RRA results are comparable to that of an established radioimmunoassay (RIA), it provides a sensitive and rapid alternative to the more time consuming RIA. PMID- 1745106 TI - Inhibition of human blood aldehyde dehydrogenase activity by cigarette-smoke condensate. AB - The effect of a cigarette-smoke condensate (CSC) and three CSC subfractions on the aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity in human blood cells was examined under physiological conditions in vitro. Incubation of intact or sonicated cells with different concentrations of crude CSC resulted in a dose dependent reduction of the ALDH activity. The inactivation was only restored in part after extensive washing of the cells, indicating that the inhibition observed was mainly irreversible. The nonvolatile (NV) subfraction of the CSC caused a reduction in ALDH activity similar to that obtained with crude CSC, while the semivolatile (SV80) and volatile (SV20) subfractions did not significantly affect ALDH. The present results, showing that the human blood cell ALDH is inactivated by constituents of cigarette smoke in vitro, suggest that the blood ALDH activity reduction found in habitual smokers is also caused by components formed during the combustion of tobacco. PMID- 1745107 TI - Preferential loss of body fat during starvation in dietary obese rats. AB - This study was undertaken to examine whether diet-induced obesity alters the amount and/or composition of weight lost during starvation. The amount and composition of weight lost during a 4-day period of starvation was determined before and at 17, 30 and 42 weeks after rats (350 g of body weight) were given a high fat diet (HFD). To control for effects of aging, a second group of rats, fed standard laboratory chow, was also subjected to similar periods of starvation. Although total weight loss during starvation was never greater for HFD rats than for chow-fed rats, the former group showed a clear patter of increasing loss of body fat and total energy and conservation of fat-free tissues with periods of starvation later in life. In addition, chow-fed rats showed substantial energy conservation during each period of starvation (i.e. they lost less energy each day than their pre-starvation energy requirements). In contrast, HFD rats demonstrated substantial energy conservation only at 17 weeks and not at 30 or 42 weeks; during the last period of starvation, their average daily loss of carcass energy exceeded their pre-starvation energy requirements. This suggests the increased fat mass of these rats may have led to increased fuel availability and to an increased metabolic rate during starvation. If these results are applicable to humans, the more obese subjects are likely to show greater total loss of energy than lean subjects, but show a lesser loss of lean body mass, at least initially. If protein requirements are reflected by the ability to mobilize protein during food restriction, protein requirements would be substantially lower in the dietary obese rats than in controls. In summary, diet-induced obesity leads to preferential loss of body fat and conservation of lean mass during starvation. PMID- 1745108 TI - Lack of alcohol dehydrogenase isoenzyme activities in the stomach of Japanese subjects. AB - Alcohol dehydrogenase (ADH) isoenzymes different from those of the liver were shown to be present in the human gastric mucosa. Two ADH activity bands present in the gastric mucosa of surgical specimens from all 7 black and 11 white Americans studied were absent in 14 and barely detectable in 3 of 21 Japanese subjects evaluated. Similar ethnic differences pertained to both genders and were independent of the gastric pathology. The mobility of these bands on starch gel electrophoresis corresponded to those recently reported and named mu-ADH or sigma ADH. The absence of these bands was associated with a 70% decreased capacity to reduce m-nitrobenzaldehyde, a preferred substrate for sigma-ADH, suggesting that the bands missing from the Japanese stomachs comprise this isoenzyme. PMID- 1745109 TI - Handouts: making the lecture portable. AB - Previous medical literature on preparing lecture handouts has focused on their use in student education, where as part of a course there is a series of lectures followed by an examination. Conversely, resident and practising physicians usually attend single lectures on individual topics in order to update and improve their clinical skills. Handouts designed for the latter type of lecture can serve as a useful resource in subsequent day-to-day teaching and patient care. This article examines the purpose, distribution, structure, and substance of such handouts. Guidelines to assist the speaker in preparing lecture handouts are discussed. PMID- 1745110 TI - Managing the initial period of implementation of educational change. AB - Three years ago the Universiti Kebangsaan Malaysia medical school changed its curriculum from the traditional discipline based curriculum to the integrated organ-system approach. Once change was effected a process of 'refreezing' had to be initiated whereby new responses had to be reintegrated into the ongoing personality or emotional relationships of important people so that the change process will endure and become stable. During this refreezing process the faculty encountered several problems which could thwart further development of the new curricula if left unresolved. The nature of the problems seemed to indicate that curricular change involves more than just efforts at bettering the what and ways of student learning and assessment. A lot of energy was also spent on keeping things going, keeping people motivated, making sure the work was done (at least as well as it has in the past), looking for better ways to do things, weighing new solutions and to be alert to new problems. In ensuring the continuance of change it was important to ensure, from the outset the institutionalization of policies, programmes, procedures and practices for continuing reward, routinization, structural integration into the system, continuing evaluation and providing for continuing maintenance. PMID- 1745111 TI - A novel perspective on medical education. AB - Participants on a course entitled 'Planning and Evaluating a Course' generated a theoretical framework to simplify consideration of the essential components of clinically skilled behaviour. Five superordinate facets were elucidated and elaborated with reference to specific teaching situations. This paper illustrates the effective use of buzz-groups to encourage active participation of individual group members. The exercise revealed some serious shortcomings in the current teaching of clinical skills. PMID- 1745112 TI - Teaching health promotion and illness prevention to trainee general practitioners. AB - This study demonstrates that the provision of feedback based on the observation of videotaped consultations can be used to increase self-awareness of deficiencies in health promotion and illness prevention skills. Trainee general practitioners were found to have some awareness of deficiencies in this important aspect of general practice, and this awareness increased as a result of self observation and the feedback. Performance was self-evaluated to be better at the end of the general practice term than at the beginning. PMID- 1745113 TI - Reflection in clinical teaching: an analysis of reflection-on-action and its implications for staffing residents. AB - In order to improve clinical teaching in the ambulatory care setting, clinical teachers need to know the range of instructional strategies available to them. One potentially useful strategy is that of reflection. In this paper, reflective practice will be described in the context of the professional training of physicians, with the purpose of improving clinical teaching. An example of reflective practice--a transcript of a video tape of an attending physician and a resident in a general internal medicine clinic--will be analyzed. In this transcript, reflective comments by both the attending physician and resident are integrated into the original dialogue. PMID- 1745114 TI - Teaching mental handicap to medical students. AB - An innovative approach to the teaching of mental handicap to pre-clinical medical students as part of their Behavioural Sciences course is first described. The teaching is organized around a number of extended placements which allow students to interact with people with a mental handicap on a basis of equality and reciprocity. Students respond positively to the seminar, regarding it as enjoyable, interesting and relevant to their future work as doctors. Questionnaires administered to students participating in the seminar suggest that they have a generally positive image of mentally handicapped people and hold vaguely liberal views as to how they should be treated by Society. Few, however, wish to work in the mental handicap area. There is no evidence that the experience of the seminar leads to any significant change in these attitudes. PMID- 1745115 TI - What is missing from patient histories? AB - Second year students' proficiency in history taking was evaluated by the Objective Structured Clinical Examination (OSCE) and a written test, with particular attention to Risk Factors and Psychosocial Data. Students concentrated on obtaining Diagnostic Information on both tests, but those students who worked with preceptors in the community, (PCC program), included a wider range of data. Overall performance was higher on the OSCE which emphasized diagnostic information. Student histories tend to exclude Risk Factors and Psychosocial Data unless their inclusion is modeled and expected by faculty. PMID- 1745116 TI - The use of the objective structured clinical examination as an audit of teaching and student performance. AB - A four year experience of the Objective Structured Clinical Examination in Child Health of 301 students in 18 separate examination diets was analysed to determine student competence in several clinical examinations including cardiovascular and central nervous system, developmental examination, history of asthma and in answering multiple choice questions relating to factual information. Using criterion reference assessment, student performance was related to individual knowledge, quality of teaching, examination design and teacher expectation. Variable levels of expectation and achievement were noted for different clinical items. Staff expectation of student performance was found to be higher than achieved in 39%, the same in 55% and in only 6% did students perform better than was anticipated. The value of using Criterion Reference Assessment System, based on a standard comprehensive examination, is discussed in relation to influencing examination design and efficiency of teaching medical students. PMID- 1745117 TI - An analytical model for the design of RF resonators for MR body imaging. AB - A closed form, analytical solution describing the RF fields generated by an RF body coil resonator for MR imaging at 1.5 and 4.0 T is presented. This solution extends the results of earlier studies of RF penetration in the body by explicitly including the RF coil, the RF shield, and the field variation along the z axis for high-pass bird cage coils. A salient feature of this treatment is the calculation of the axial propagation constant, kz, which determines the z dependence of the RF field. We have determined the relative power deposition in the body, the B1 field homogeneity, and coil losses, which are functions of the coil-to-shield separation and body size. The relative power deposition in the body has been calculated to vary as the 1.58 power of the body radius. The calculations have also predicted that the field homogeneity in the z direction exhibits greater degradation at higher frequencies in a high-pass coil than in a low-pass coil. The model predicts an increase in coil losses by a factor of 2.8 as the coil-to-shield separation is reduced from 5 to 2 cm in a standard body resonator. Although the results for only a homogeneous cylindrical object or body are presented, the theory can be extended to a multilayered heterogeneous object of varying permittivity and conductivity. PMID- 1745118 TI - Evaluation of energy metabolism in brain using epimerization of 2-deoxy-2-fluoro D-glucose by 19F NMR: the effect of anesthesia. AB - The effect of anesthesia on the epimerization of 2-deoxy-2-fluoro-D-glucose(-6 phosphate) to 2-deoxy-2-fluoro-D-mannose(-6-phosphate) in mice was demonstrated with 19F NMR spectroscopy of excised tissue specimens from heart, muscle, and brain. Spectra from each of six excised organs confirmed that pretreatment with an anesthetic suppressed the conversion ratio, FDM/(FDG + FDM), in brain at 3 h from 52 +/- 5 to 30 +/- 6% under the dose of 100 mg/kg. We propose potential applications for NMR monitoring of FDG-FDM conversion, including the assessment of regional brain metabolism and the evaluation of various pharmacologic agents. PMID- 1745119 TI - Human auditory system response to pulsed radiofrequency energy in RF coils for magnetic resonance at 2.4 to 170 MHz. AB - The threshold conditions for an auditory perception of pulsed radiofrequency (RF) energy absorption in the human head have been studied on six volunteers with RF coils for magnetic resonance (MR) imaging. For homogeneous RF exposure with MR head coils in the 2.4- to 170-MHz range and pulse widths 3 microseconds less than or equal to Tp less than 100 microseconds, the auditory thresholds were observed at 16 +/- 4 mJ pulse energy. Localized RF exposure with optimized surface coils positioned flush with the ear lowers the auditory threshold to only 3 +/- 0.6 mJ. The hearing threshold of RF pulses with Tp greater than 200 microseconds occurs at more or less constant peak power levels of typically 150 +/- 50 W for head coils and as low as 20 W for surface coils. The results from this study confirm theoretical predictions from a thermoelastic expansion model and compare well with reported thresholds from near field antenna measurements at 425 to 3000 MHz. Details of the threshold dependence on RF pulse length reveal primary sites of RF to acoustic energy conversion at the mastoid and temporal bone region and the outer layer of the brain from where thermoelastically generated pressure transients excite audible pressure waves at the resonance modes of the skull around 1.7 kHz and of the brain around 11 kHz. If not masked by usually dominating noise from switched gradients, the conditions for hearing RF pulses, as applied to head coils in MR studies with flip angle alpha at main field B0, is given by Tp/ms less than or equal to 0.4 (alpha/pi)B0/[T]. At peak power levels up to 15 kW presently available in clinical MR systems, there is no evidence known for detrimental health effects arising from the RF auditory phenomenon which is a secondary cause associated with primary RF to thermal energy conversion in body tissues. To avoid the RF-evoked sound pressure levels in the head rising above the discomfort threshold at 110 dB SPL, an upper limit of 30 kW applied peak pulse power is suggested for head coils and 6 kW for surface coils. PMID- 1745120 TI - Toward fully automatic estimation of in vivo 31P spectra. AB - Fitting a model to an experimental spectrum is a difficult nonlinear estimation problem. The solution presented here is to start an iterative search procedure sufficiently close to the optimal model parameter set. This is achieved by providing tissue-dependent a priori peak information and by a novel correlation method to get good primary estimates of the resonance and phase offset parameters. The resulting estimation procedure is fully automatic and has proven to be robust for 31P data. PMID- 1745121 TI - A lineshape fitting model for 1H NMR spectra of human blood plasma. AB - A lineshape fitting model was constructed for classifying the overlapping information in the 1H NMR spectrum of human blood plasma. A reliable assignment of the overlapping fatty acid (-CH2-)n and -CH3 resonances of the various lipoproteins (VLDL, very low density lipoprotein; LDL, low density lipoprotein; HDL high density lipoprotein) is introduced, and for the first time detailed characteristics (chemical shifts, half linewidths, and relative intensities) of the individual lipoprotein components were obtained directly from the whole plasma spectrum. This was achieved by combining the constructed lineshape fitting model and the proper 400 MHz proton NMR measurements from blood plasma of a healthy donor, from fractions of the different lipoproteins, and from plasma samples in which the lipoprotein fractions were separately added. The results suggest fair promise of future applications of the rapid and easy NMR analysis of lipoprotein distribution in various research and clinical situations. PMID- 1745122 TI - Quantitative determination of the partial oxygen pressure in the vitrectomized rabbit eye in vivo using 19F NMR. AB - We have quantitatively determined the PO2 within the vitreous space of the vitrectomized rabbit eye in vivo using 19F NMR and perfluorotributylamine (FTBA). The results of the present work are in good agreement with previous measurements of PO2 within the nonvitrectimized rabbit eye obtained using oxygen microelectrodes. In this study, good precision and accuracy were achieved by: (1) having minimal flow effects present, (2) optimizing the signal-to-noise through the use of neat FTBA and surface coil transmission and detection, and (3) performing an inversion-recovery pulse sequence, with adiabatic pulses, to optimize the dynamic range of the T1 experiment. Possible deleterious effects on the measured T1 due to the vitreal temperature gradient are discussed. To the best of our knowledge the results of this study demonstrate, for the first time, a quantitative determination of intraocular PO2 in vivo using 19F NMR and FTBA. PMID- 1745123 TI - Quantitative measurement of blood flow using cylindrically localized Fourier velocity encoding. AB - A procedure for the quantitative measurement of blood velocity was developed and evaluated in the portal vein, aorta, and vena cava of healthy volunteers. This procedure utilizes Fourier velocity encoding and can be performed with or without cardiac gating. The accuracy of velocity measurements is determined by the accuracy of the gradient subsystem. Flow measurements derived from the velocity measurement are further limited in their accuracy by the luminal cross-section measurement. Spatial localization is accomplished with an excitation pulse having a cylindrical rather than slab geometry. Data are acquired in the presence of a readout gradient to provide resolution along the cylindrical axis. PMID- 1745124 TI - Spoiling of transverse magnetization in steady-state sequences. AB - A detailed analysis is presented of a method to eliminate transverse magnetization prior to each rf excitation in pulse sequences with TR less than T2. It is shown that artifact-free images with high T1 contrast can be obtained only if a phase shift that is incremented during each TR interval is applied to the transverse magnetization. Computer simulations are used to show that when this phase increment is 117 degrees, the steady-state transverse magnetization prior to each rf pulse is nulled over a wide range of T1, T2, and rf tip angles, resulting in optimal T1 contrast. Such nulling of steady-state transverse magnetization cannot be obtained by using large gradient pulses, or gradients of random or linearly incremented amplitude. Images of phantoms and human subjects confirm the theoretical predictions. PMID- 1745125 TI - Pulsed NMR relaxometry of striated muscle fibers. AB - The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation of fast- and slow-twitch muscle fibers are examined using rat muscle tissues in which one fiber type predominates. Both continuum and discrete exponential component fits are made to Carr-Purcell-Meiboom-Gill (CPMG) and inversion recovery pulse sequence measurements. In addition, experiments which illustrate the large sources of variability that have led to apparent conflicts in the literature are presented. Based on the results of this study, unique NMR features that distinguish fast- and slow-twitch muscle fibers are presented. The feasibility of differentiating fast- and slow-twitch muscle fibers using magnetic resonance (MR) imaging is briefly discussed. PMID- 1745126 TI - Snapshot imaging using a FLARE sequence. AB - We have implemented a snapshot FLARE sequence using a scan time of 320 ms for a 64 x 128 image. As in the conventional FLARE sequence the T2 weighting of the image can be altered by manipulating the phase encoding scheme with the position of the zeroth phase encoding effectively determining the amount of T2 weighting. Reducing the flip angle of the refocusing pulse reduces both the RF power deposition and the blurring in images of short T2 samples, at the expense of reduced signal and contrast. PMID- 1745127 TI - Filtering noise from images with wavelet transforms. AB - A new method of filtering MR images is presented that uses wavelet transforms instead of Fourier transforms. The new filtering method does not reduce the sharpness of edges. However, the new method does eliminate any small structures that are similar in size to the noise eliminated. There are many possible extensions of the filter. PMID- 1745128 TI - Hexagonal surface gradient coil for localized MRS of the heart. AB - A surface gradient coil designed to obtain localized magnetic resonance spectroscopy of the heart in vivo is described. Images and 31P spectra from phantoms and both pig and dog hearts in vivo are shown. The coil was used in conjunction with a rf surface coil to obtain 31P spectra from transmural sections of the left ventricular wall of a dog heart in vivo to demonstrate differences between normal and ischemic tissue. PMID- 1745129 TI - Localized proton NMR observation of [3-13C]lactate in stroke after [1-13C]glucose infusion. AB - To assess whether elevated lactate in stable stroke is being actively produced from blood glucose localized 1H NMR stimulated echo spectra were obtained from a patient in the region of a 32-day-old cortical infarct before and 60-100 min after infusion of [1-13C]glucose. Prior to the infusion the spectrum from the region of the infarct contained an elevated resonance from C3 lactate and a greatly reduced resonance from N-acetyl groups relative to an unaffected contralateral region. After the infusion two additional resonances were observed at 62 and -64 Hz relative to the unlabeled resonance of C3 lactate which were assigned on the basis of chemical shift and relative intensity to [3-13C]lactate. The [3-13C]lactate fractional enrichment in the infarct region was measured to be 32% which is within error one-half the average [1-13C]plasma glucose enrichment during the postinfusion NMR measurement. The result suggests that the stroke lactate pool was completely derived from infused glucose. PMID- 1745130 TI - Sensitivity enhancement and reduction of Gibbs artifact in T2-weighted imaging using variable tip angle excitation. AB - Introduction of a Gaussian weighting function into the phase encoding of the spin echo imaging method via variable tip angle excitation, with concomitant optimization of the recycle delay, is shown to increase the sensitivity of T2 weighted imaging by up to 40%. In addition, the Gibbs artifact associated with sharp boundaries is reduced considerably without the need for postprocessing of the data. PMID- 1745131 TI - In vivo measurement of cerebral oxygen consumption and blood flow using 17O magnetic resonance imaging. AB - We used 17O NMR imaging techniques to measure the H2(17)O concentration in a 0.8 ml voxel in the cat brain following injection of an arterial bolus of enriched H2(17)O and during inhalation of enriched 17O2. We also measured the H2(17)O concentration in arterial blood during 17O2 inhalation. The data from the first measurement were used to calculate the blood flow in the voxel. The data from all three measurements were combined to calculate the oxygen consumption in the voxel. The values of cerebral blood flow and oxygen consumption calculated with 17O NMR techniques agree reasonably well with values calculated for a similar region of the cat brain using autoradiographic techniques. PMID- 1745132 TI - A clinically viable technique of fat suppression for abdomen and pelvis. AB - Chemical-shift selective imaging with an improved selective presaturation pulse can be used to suppress the fat signal uniformly across the entire abdominal cavity. The required magnetic field homogeneity is no higher than for a routine diagnostic scan. Therefore, no extra setup time for shimming is needed. The technique has been implemented on our clinical system for routine fat suppression scans. PMID- 1745133 TI - Expenditures and sources of funds for mental health organizations: United States and each state, 1988. AB - Expenditures. Expenditures by the 8 types of mental health organizations covered in this report totaled $23.1 billion in 1988 in the United States and territories. Three States (California, New York, and Pennsylvania) accounted for 30 percent of this total. Nationally, State and county mental hospitals (hereafter called State mental hospitals) accounted for the largest proportion of all expenditures (30 percent, down from 34 percent in 1986). Private psychiatric hospitals and multiservice mental health organizations had the next largest expenditures, each accounting for 20 percent of the total, followed by the separate psychiatric services of non-Federal general hospitals at 16 percent. Department of Veterans Affairs (VA) mental health services, residential treatment centers (RTCs) for emotionally disturbed children, freestanding psychiatric outpatient clinics, and freestanding psychiatric partial care organizations accounted for 6 percent, 6 percent, 3 percent, and less than one-half percent of total expenditures, respectively. State mental hospitals represented the largest expenditures of any single type of mental health organization in 23 States; expenditures of private psychiatric hospitals were largest in 12 States; and expenditures of multiservice mental health organizations were the largest in 10 States. The $23.1 billion total for 1988 represented a 25 percent increase over the 1986 figure but, when adjusted for inflation, the estimated increase (expressed in constant dollars) was only 10 percent overall and 8 percent on a per capita basis. Constant dollar expenditures of most types of mental health organizations increased between 1986 and 1988, with the largest increase occurring among private psychiatric hospitals (54 percent). In contrast, constant dollar expenditures decreased for State mental hospitals and VA mental health services. Sources of Funds In 1988, the funds received by mental health organizations totaled $23.4 billion. Of this total, $8.8 billion (38 percent) was provided directly by State governments, predominantly by State mental health agencies. Direct Federal funds, plus Medicare and Medicaid (including the State and local share of Medicaid), provided $6.5 billion (28 percent) of total funding. Fees from clients (including private insurance) provided $5.2 billion (22 percent); direct local government funds provided 7 percent; and all other sources, 5 percent. State governments provided 77 percent of the funds received by State mental hospitals and were also the largest single source of funds for multiservice mental health organizations (51 percent) and freestanding psychiatric partial care organizations (44 percent). VA mental health services were funded by the Federal government, while 62 percent of funding for private psychiatric hospitals came from client fees (including private insurance).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745134 TI - Outpatient care programs of mental health organizations, United States, 1988. AB - In 1988, 2,989 (60 percent) of the 4,961 mental health organizations in the United States (including the territories) offered outpatient care programs. A total of 5.8 million patient care episodes were generated by these organized outpatient programs. These episodes included 3.1 million outpatient additions, produced 54 million outpatient visits, and represented 67 percent of all patient care episodes in mental health organizations in 1988. Although the number of mental health organizations with outpatient care programs increased by less than one percent between 1986 and 1988, the number of outpatient additions showed an 11 percent gain during this period. Multiservice mental health organizations were the primary locus of outpatient care in 1988, accounting for 41 percent of the 2,989 mental health organizations providing this care. Ranking next in this respect, were free-standing psychiatric outpatient clinics, and the separate psychiatric outpatient services in non-Federal general hospitals, with 25 and 16 percent, respectively, of the total outpatient care programs. In general, these three organization types had similar rankings with respect to the volume of the outpatient caseload. By definition, all of the freestanding psychiatric outpatient clinics provided outpatient care, and almost all of the VA mental health programs and multiservice mental health organizations also offered this care (99 and 92 percent, respectively). In contrast, psychiatric outpatient care was available in only 37 percent of non-Federal general hospitals with separate psychiatric services, 36 percent of private psychiatric hospitals, 29 percent of State mental hospitals, and 22 percent of RTCs for emotionally disturbed children. Outpatient care was available in mental health organizations in all States in 1988, with every State having at least two or more organization types providing this service. In general, the most populous States had the largest number and the greatest variety of mental health organizations with outpatient care programs. Of the 2.87 million clients receiving outpatient care in mental health organizations at the end of 1988, 23 percent were under 18 years of age, 68 percent were 18 to 64, and 9 percent were 65 and older. Male outpatient clients slightly outnumbered female clients. The majority (77 percent) of the outpatient clients were white, with blacks representing 21 percent; native Americans and Asians/Pacific Islanders, the remaining two percent. Eleven percent of the total client population were reported to be of Hispanic origin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745135 TI - Characteristics of persons served by private psychiatric hospitals, United States: 1986. AB - Overall about 71,000 persons were under care in the inpatient, outpatient, and partial care programs of private psychiatric hospitals in the United States on April 1, 1986, and about 300,000 persons were admitted to these programs during 1986. Inpatient programs served the largest number of people, 223,851; outpatient programs served 133,217; and partial care programs served a much smaller population, only 13,541. The relative distribution of persons admitted, versus persons under care, differed considerably by type of program. Although the number of those admitted was larger than the number of those under care for both inpatient and outpatient programs, the difference between the two populations was much more pronounced within inpatient programs (chart A). Most of the persons admitted to private psychiatric hospitals in 1986 were admitted to inpatient programs, 207 thousand or 69 percent of all admissions, while most of those under care were outpatients, 47 thousand or 66 percent of all those under care on a single day. Children and youth under age 18 comprised the largest percentage of persons under care in inpatient programs, while persons in the 25-44 age group comprised the largest percentage of those admitted to inpatient programs. Approximately 41 percent of all persons under care in inpatient programs were under 18 years of age, compared with only 20 percent of all persons admitted to inpatient programs. The large number of children and youth found in the population under care within inpatient programs indicates the high median length of inpatient stay for persons within this age group (41 days compared with 24 days overall). Children and youth and the 25-44 year group each represented over one-third of those admitted to outpatient programs. The 25-44 age group made up the largest percentage of persons under care in outpatient programs and among those admitted to partial care programs. Among those under care within partial care programs, differences among age groups were not statistically significant. Of persons admitted to partial care programs, 92 percent had a history of some type of prior mental health treatment; for those admitted to inpatient and outpatient programs, the corresponding percentages were 70 percent and 48 percent, respectively. Affective disorders were a frequently occurring diagnostic grouping, comprising almost half of all persons admitted to and under care in inpatient programs, approximately one-third of those admitted and those under care in partial care programs, and around one-fourth of those admitted to and under care in outpatient programs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745136 TI - The failure of prevention. PMID- 1745137 TI - Mental retardation: new realities, new challenges. PMID- 1745138 TI - Use and impact of a cash subsidy program. AB - The use and impact of a $256.74 monthly cash subsidy by 1,283 families with children who have severe disabilities were examined. Families reported a variety of uses, including the purchase of clothing, toys, sitters, diapers, special foods, adaptive equipment, and professional services. Families at lower income levels used the subsidy to meet basic needs more often than did families at higher income levels. Families indicated that the subsidy was very helpful in meeting special needs and had improved family life, eased financial worries, and reduced stress. The influence of the availability of the subsidy on continuing family-based care was examined. PMID- 1745139 TI - Historical look at nursing in the field of mental retardation in the United States. AB - An account of nursing in the field of mental retardation was examined. Educational preparation, professional identity, workday, and salaries were discussed. The influence of attitudes towards persons with mental retardation on this nursing specialization was emphasized. PMID- 1745140 TI - Language analysis skills of children with mental retardation. AB - The ability of children with moderate mental retardation to analyze orally presented sentences into words and words into syllables and phonemes was studied. The subjects, aged 10 to 15, were grouped by method of reading instruction. All of them could analyze spoken sentences into words and words into syllables equally well. However, subjects receiving code-emphasis reading instruction performed significantly better on the more difficult phoneme manipulation tasks than did subjects receiving whole-word instruction. Results suggest that code emphasis reading instruction for some subjects with mental retardation should be used. Further research on linguistic analysis skills and the use of code-emphasis reading instruction in conjunction with linguistic awareness training with this population is warranted. PMID- 1745141 TI - Reimbursement of ICFs/MR program costs based on client resource use. AB - In this article we have described the impetus, research, and recommendations for a new reimbursement system based on client resource use for ICFs/MR in Minnesota. Research to develop a targeted reimbursement strategy has been completed and a proposal for basing program rates on client resource use developed. Residents (N = 913) in a stratified sample of 65 facilities were assessed and staff resource use determined. Results showed that although predictors in the area of personal interaction, integration, and independence, activities of daily living, special treatment/medical complexity, and behavior accounted for a significant amount of variation in resource use, the unaccounted for variation was sufficiently large to support recommending a system that will base program rates on individual client resource use and the historical costs of individual facilities. Key design issues were also discussed. PMID- 1745142 TI - Permanency planning by older parents who care for adult children with mental retardation. AB - In a study of 57 older parent caregivers of adult children with mental retardation, more than half had not planned for their child's future care. Income, race, child's gender and level of adaptive behavior, and degree of parental interaction with relatives and friends were significantly related to future care-planning activity. PMID- 1745143 TI - [Photodamage of gram-positive and gram-negative bacterial cells in the presence of chlorin e6 derivatives]. AB - The kinetics of photoinduced damage sensitized by chlorine e6 and its derivatives was studied in Escherichia coli and Bacillus subtilis. The effectiveness of E. coli photoinactivation in the presence of chlorines was 100-200 times lower as compared with that of B. subtilis. The structural organisation of bacterial cell walls apparently played an essential role in the penetration of tetrapyrrole pigments into the cell and in their binding. PMID- 1745144 TI - [Detection of a wild population of yeast of the biological species Saccharomyces cerevisiae in Siberia]. AB - A wild yeast population of Saccharomyces cerevisiae was found for the first time in Siberia, as was confirmed by hybridological analysis. The European cultivated S. cerevisiae strains were demonstrated to take their origin from Asia. PMID- 1745145 TI - [Determination of the immune potency of lymphocyte-promoting factor (LPF) and filamentous hemagglutinin (FHA) molecules by intranasal challenge in mice]. AB - All mice immunized with toxoid LPF and FHA molecules were found to be protected against infections by intranasal instillation of Bordetella pertussis. While a significant weight loss was observed in control mice within ten days following challenge, immunized mice were found to gain weight. Mice immunized with 20 micrograms doses of toxoid LPF were found to be also protected against intracerebral infection. FHA did not protect mice against such an infection. PMID- 1745146 TI - [Staphylococcal protein A, bacteriocin, DNase and lactamases of methicillin resistant Staphylococcus]. AB - 231 Methicillin-Resistant Staphylococcus (MRS) and 76 Methicillin-Susceptible Staphylococcus (MSS) strains were investigated for Staphylococcal Protein A, bacteriocin, DNase and beta lactamase production properties. It was found that 73.6% of the strains of MRS were positive for protein A, 3.8% for bacteriocin, 76.2% for DNase and 84.4% for beta lactamase production. And it was found that 61.8% of MSS strains were positive for protein A, 11.8% for bacteriocin, 55.2% for DNase and 57.9% for beta lactamase production. Staphylococcal protein A, DNase and lactamase production. Staphylococcal protein A, DNase and lactamase production were found to be significantly higher in MRS strains than MSS strains and bacteriocin production was found to be higher in MSS strains than MRS strains according to Chi Square Test. PMID- 1745147 TI - [Comparison of two different media-atmosphere combinations on the isolation of group A beta-hemolytic streptococci from throat cultures]. AB - In this study effects of incubation of sheep blood agar medium in aerobic conditions and incubation of sulfamethoxazole-trimethoprim containing sheep blood agar medium in 5 to 10% CO2, of the isolation of group A beta hemolytic streptococci from throat cultures were compared. 608 throat swab specimens were studied. Each agar medium was evaluated after 24 and 48 hours of incubation period. The aerobic incubation of sheep blood agar plates for 24 hours yielded 108 (17.7%) strains of beta hemolytic streptococci, of these 96 (15.8%) strains being group A. 113 (18.5%) strains of beta hemolytic streptococci were isolated after 48 hours of incubation and 100 (16.4%) of these were group A. The number of beta hemolytic streptococci isolated in 5 to 10% CO2 atmosphere for 24 hours was 62 (10.2%), and 57 (9.3%) of these were group A. When the incubation period was prolonged to 48 hours, the total number of beta hemolytic streptococci isolated increased to 82 (13.5%) and 76 (12.5%) of these were determined as group A. The difference between these two combinations was significant for 24 hours of incubation, but not significant for 48 hours of incubation. The highest isolation rate for group A streptococci was achieved in aerobic incubation of sheep blood agar plates for 48 hours. PMID- 1745148 TI - [The value of laboratory tests for the early diagnosis of newborn sepsis]. AB - In our study, laboratory tests were evaluated in the early diagnosis of newborn sepsis. The study consisted of 53 newborn infants with the diagnosis of suspected sepsis. Of the 53 newborn infants twenty seven were excluded from the study, because of negative blood culture. Remaining 26 newborns with positive blood culture and 15 healthy newborns comprised the study (sepsis group) and control group respectively. Total mature neutrophil count, immature/total neutrophil and immature/matur neutrophil ratio, toxic granulation changes, serum level of C reactive protein and haptoglobin were found statistically higher in sepsis group than control group. Thrombocyte count and serum level of IgG were significantly lower in sepsis group. Average total white blood cell count, result of nitroblue tetrazolium tests erythrocyte sedimentation rate and serum level of IgM was similar in both groups. We emphasized that hematological scoring system, serum level of C-reactive protein and haptoglobins can be used in the early diagnosis of newborn sepsis. PMID- 1745149 TI - [Effect of antisperm antibodies in male infertility]. AB - Antisperm antibodies and their relationship with infertility has been investigated in semen and serum samples of 100 infertile and 25 fertile males. The investigation of antisperm antibodies has been done by latex agglutination test in semen samples and by ELISA procedure in serum samples. In addition, the semen samples have been investigation for several characteristics. Antisperm antibodies have been found 7% positive in blood and 30% positive in semen. In 28.5% of the patients with positive antisperm antibodies in blood, antisperm antibodies in semen have also been found to be positive. For cases with infertility of unknown cause the antisperm antibodies ratio has been found to be significantly high (p less than 0.002). These results have shown the importance of further investigation of antisperm antibodies in cases with infertility of unknown reasons. PMID- 1745150 TI - [Distribution characteristics of hepatitis B surface antigen positivity in Bursa]. AB - The ratio of HBsAg positivity among 9978 healthy blood donors by indirect hemagglutination (IHA) method was 4.8%. Positivity was 4.4% among donors coming from districts in Bursa. Positivity was higher among donors coming from boarding societies and villages (6.1% and 8.1%), they were significant (p less than 0.05 and p less than 0.001). The highest positivity was found at the age group between 16-25 years (6%). With older ages, positivity becomes less (at the age over 46 ratio was 2.5%) and it was significant (p less than 0.001). PMID- 1745151 TI - [E. coli strains producing heat labile enterotoxin on Vero cells]. AB - In this study heat-labile toxin (LT) producing strains of Enterotoxigenic Escherichia coli (ETEC) have been investigated by using Vero cell-line, which were isolated predominantly from the cultures of stool samples of 100 infants, aged between 0-2, with diarrhea. Among these strains 3% were found as toxin producers. These 3 strains were also detected as toxin producers and serotyped as O?:H12,LT(+); O?:H53,LT(-); (0126):H27,(LT)(-) at Statens Serum Institute (Denmark) International Escherichia and Klebsiella Centre. PMID- 1745152 TI - [Staphylococcus aureus nasal carriage in the normal population and hospital laboratory personnel]. AB - Hospital personnel may be nasal carriers of S.aureus in a higher percentage of cases than in the general population. The aim of the present study was to compare the rate of nasal carriage of S.aureus in general population and hospital laboratory personnel. 144 of patients sent to our Microbiology laboratory for other reasons (i.e., Urine Culture, serology, etc.) were taken as general population, and 38 person from Microbiology, Biochemistry, Hematology, Immunology and Pathology Laboratories of our hospital were included the study as hospital laboratory personnel. S.aureus nasal carriage rates were found 28% (41/144) in normal population, and 31.5% (12/38) in hospital laboratory personnel. These figures are between normal population range. Therefore the rate of nasal carriage of S.aureus in our hospital, reflects probably normal population carrier rate, not the hospital colonization. PMID- 1745153 TI - [Salmonella enteritidis serovar tarshyne strains isolated from fecal specimens]. AB - Seven Salmonella enteritidis serovar tarshyne strains were isolated from fecal specimens in 1989 and 1990 summer months. PMID- 1745154 TI - [A new respiratory tract pathogen]. AB - Chlamydia pneumoniae strain TWAR, a newly described Chlamydia organism is a common cause of pneumonia and other acute respiratory tract infections. Most TWAR infections are mild or asymptomatic, but occasionally severe pneumonia in elderly patients or with on going chronic diseases has been observed. Population antibody prevalence has shown that TWAR infection is world-wide infection and an important health problem since under-developing countries where the high rate of child death is predominant, TWAR infections cause acute respiratory tract infection in children who are less than 5 yrs of age. Re-infection during life-time emphasizes the importance of Chlamydia pneumoniae. PMID- 1745155 TI - [Identification and treatment of group A beta-hemolytic streptococcus]. AB - We examined the current developments and studies on identification, treatment and carrier states of group A beta haemolytic streptococcus, depending on the literature. PMID- 1745156 TI - The past, present and future of medicine. PMID- 1745157 TI - Doctors and genetic manipulation. PMID- 1745158 TI - Malaria prevention for travellers. PMID- 1745159 TI - The case for graduate schools of medicine in Australia. AB - The present length of the medical curriculum in Australia is, with one exception, six years. It is argued that the time is ripe for the development of some four year graduate schools from among the existing ten medical schools. Selection from a pool of university graduates would permit a greater degree of self-selection of motivated students able to perform well in tertiary studies. At present admission to medicine occurs mainly direct from secondary school. It is argued that graduate students entering medicine would be more broadly educated, more mature and more self-directed in their studies and career selection. The curricula of such graduate schools could foster better integration of scientific knowledge and clinical practice. Such graduate schools would be concordant with current priorities of national policies on higher education. PMID- 1745160 TI - The new pathway in general medical education at Harvard Medical School. PMID- 1745161 TI - Workshop on evaluating the undergraduate medical curriculum. PMID- 1745162 TI - The Flinders experiment in medical education revisited. AB - OBJECTIVE: The undergraduate medical curriculum of the Flinders University of South Australia is reviewed and evaluated against American recommendations for the basic education of doctors practising in the 21st century. DATA SOURCES: Two previous articles in The Medical Journal of Australia describing earlier versions of the Flinders curriculum and the report on General Professional Education for the Physician of the Association of American Medical Colleges. DATA SYNTHESIS: The Flinders curriculum attempts to fully integrate the teaching of medical science and clinical disciplines. The earliest version of the curriculum emphasised horizontal integration of normal structure and function of body systems, followed by abnormalities of these systems, and finally clinical practice. The second version introduced vertical integration of basic science and clinical medicine within a body system. The present version attempts to balance the demands of horizontal and vertical integration. An important feature of all versions is the large proportion of time allowed for elective studies in most years of the course. CONCLUSIONS: The Flinders curriculum has been able to adapt to the changing needs of medical education because its organisation is relatively free from the constraints of departmental rivalry over resources. PMID- 1745163 TI - Lead poisoning--a family study. AB - OBJECTIVE: A family study is used to highlight the varied manifestations of lead poisoning and difficulties in diagnosis and treatment. CLINICAL FEATURES: A 42 year-old Italian woman with a known beta-thalassaemia trait presented with a two year history of disabling pains and symptomatic anaemia, which were found to be caused by lead poisoning. INTERVENTION AND OUTCOME: Screening for lead poisoning among her immediate family members identified two others with different manifestations of plumbism. All three needed active chelating, which resulted in resolution of their symptoms. CONCLUSIONS: The similar haematological findings of beta-thalassaemia and lead poisoning may lead to a delay in diagnosis and treatment of lead poisoning when these two conditions coexist. PMID- 1745164 TI - Acoustic neuroma. AB - OBJECTIVES: To present the clinical features, the diagnostic methods, and the techniques and results of surgical removal of acoustic neuromas, and to illustrate the lowered mortality and morbidity derived from improved imaging and the improved surgical results from a teamwork approach. DESIGN, SETTING AND PATIENTS: We review our consecutive series of 106 patients undergoing 119 operations for acoustic neuroma at Royal Prince Alfred Hospital in Sydney between 1977 and 1988. RESULTS: Forty-two operations were standard posterior fossa craniectomies. The mortality was 9.5%, preservation of facial nerve function was achieved in 48% of patients, and complete removal of tumour in 66% (42% of patients had a tumour larger than 3.5 cm). A translabyrinthine approach was used in 27 patients, with a mortality of 14% and no improvement in preservation of facial nerve function. The middle cranial fossa approach was used in six patients without mortality but with no better result in preservation of nerve function. The retrosigmoid approach was used in 44 patients with no mortality and preservation of facial nerve function in 86% of patients. CONCLUSIONS: Improved imaging and earlier diagnosis have led to improved surgical results, both in terms of reduced mortality and morbidity and in the preservation of function, particularly of the facial nerve, and at times also of hearing (mostly in patients with small tumours). The surgical results have been substantially improved by the formation of a cohesive and effective neuro-otology team to perform this intricate and protracted surgery. PMID- 1745165 TI - Imported malaria in Australia. AB - OBJECTIVE: To obtain information on imported malaria in Australia. DESIGN AND SETTING: Patients with malaria diagnosed by microscopy by laboratories in southeast Queensland and northern New South Wales between October 1987 and December 1988 were included in this study. The chi 2 test was used to analyse data. PATIENTS: Blood films, details of prophylactic regimens and clinical history were received from 146 patients. MAIN OUTCOME MEASURES: This study was to determine the percentage of patients infected with each malaria species, where they contracted their infections, whether they had taken appropriate prophylactic agents and to determine the relationship between parasitaemia and previous exposure, symptoms and prophylaxis. RESULTS: One hundred patients (68.5%) had Plasmodium vivax malaria and 33 patients (22.6%) had Plasmodium falciparum malaria, with 3 (2.1%) infected with both of these malaria species. Ten cases (6.8%) were presumptively diagnosed as infections but diagnosis by microscopy was uncertain. Seventy-four per cent of the P. vivax infections and 85% of the P. falciparum infections were contracted in Papua New Guinea. Patients presented with a range of blood parasite concentrations that did not correlate with their symptoms, previous infection with malaria (P greater than 0.25) or the regular taking of prophylactic drugs (P greater than 0.1). Only 41% of the patients took any prophylactic drugs; the figure for temporary visitors to malarious areas was 54%. Only 11.6% of patients were taking the recommended drugs for the malarious areas they visited or were resident in. CONCLUSIONS: Constant monitoring of malarial infections is needed to ensure that appropriate advice is given to the traveller. Our study supports the dogma that malaria should be suspected in all patients who have been to malarious areas, regardless of previous malarious attacks, prophylaxis, treatment or the time which has elapsed since leaving the area. PMID- 1745166 TI - Heart attacks and the Newcastle earthquake. AB - OBJECTIVE: To test the hypothesis that stress generated by the Newcastle earthquake led to increased risk of heart attack and coronary death. DESIGN: A natural experiment. SUBJECTS: People living in the Newcastle and Lake Macquarie local government areas of New South Wales, Australia. INTERVENTION: At 10.27 a.m. on 28 December 1989 Newcastle was struck by an earthquake measuring 5.6 on the Richter scale. OUTCOME MEASURES: Myocardial infarction and coronary death defined by the criteria of the WHO MONICA Project and hospital admissions for coronary disease before and after the earthquake and in corresponding periods in previous years. Well established, concurrent data collection systems were used. RESULTS: There were six fatal myocardial infarctions and coronary deaths among people aged under 70 years after the earthquake in the period 28-31 December 1989. Compared with the average number of deaths at this time of year this was unusually high (P = 0.016). Relative risks for this four-day period were: fatal myocardial infarction and coronary death, 1.67 (95% confidence interval [Cl]: 0.72, 3.17); non-fatal definite myocardial infarction, 1.05 (95% Cl: 0.05, 2.22); non-fatal possible myocardial infarction, 1.34 (95% Cl: 0.67, 1.91); hospital admissions for myocardial infarction or other ischaemic heart disease, 1.27 (95% Cl: 0.83, 1.66). There was no evidence of increased risk during the following four months. CONCLUSION: The magnitude of increased risk of death was slightly less than that previously reported after earthquakes in Greece. The data provide weak evidence that acute emotional and physical stress may trigger myocardial infarction and coronary death. PMID- 1745167 TI - Admissions for suspected snake bite to the Perth adult teaching hospitals, 1979 to 1988. AB - OBJECTIVE: To describe the epidemiology of snake bite in Perth, and the likelihood of envenomation. DESIGN: Information from case notes was retrospectively analysed. SETTING: Emergency medicine, teaching hospitals. PATIENTS: All patients admitted to the three adult teaching hospitals in Perth for suspected snake bite from 1979 to 1988. MAIN OUTCOME MEASURE: Systemic envenomation, was accepted as present if there were definite symptoms, signs or laboratory evidence (vomiting, abdominal pain, ptosis, convulsions, difficulty with breathing or swallowing, coagulopathy, haemolysis, rhabdomyolysis or renal failure). RESULTS: Ninety-nine patients were definitely bitten, with 53 envenomed, including three snake handlers. Thirty others may have been envenomed. Nearly half (44%) of the 82 patients with witnessed snake bite were envenomed. The dugite (Pseudonaja affinis) caused most cases of envenomation, most often producing coagulopathy only. The remainder were probably due to bites by the tiger snake (Notechis after occidentalis) and gwardar (Pseudonaja nuchalis), with one by a sea snake. The Commonwealth Serum Laboratories Snake Venom Detection Kit (VDK) enabled identification of the genus in 36% of definite cases of snake bite, and in 51% of cases of envenomation. It may occasionally produce false-positive results. The VDK is of greatest value in establishing the genus of snake in envenomed patients. CONCLUSIONS: It is suggested that a mixture of brown and tiger snake antivenom be used to treat patients envenomed by an unidentified snake in the Perth metropolitan area. This does not apply to patients bitten elsewhere in Western Australia or transferred to Perth from country regions where other snakes are more prevalent. PMID- 1745168 TI - The children of Chernobyl. AB - During the past twelve months much media attention has been focused on the plight of the children affected by the Chernobyl nuclear disaster in the Soviet Union. The visit to Australia by several groups of these children during 1991 has heightened community interest in the innocent victims of the world's worst nuclear accident. As medical adviser for one of these visits, I saw how some of the children of Chernobyl benefited from their holiday away from radioactivity. PMID- 1745169 TI - Radio aid to ships at sea. AB - OBJECTIVE: To review the first 30 months' experience in providing medical advice by radio to the masters of vessels in the Indian and Southern Oceans. The Department of Emergency Medicine at Fremantle Hospital has provided this service since October 1987. DESIGN: Details of all cases were collected prospectively. SETTING: The master of the ship communicates with the senior medical staff in the Department of Emergency Medicine by telex or radio-telephone. RESULTS: Seventy five patients were discussed in 30 months. They were aboard 68 ships from 17 nations. Forty-eight patients has spontaneous illnesses, of which 41 were classified as medical and 7 surgical. Twenty-seven patients sustained injury. The most frequent medications advised by the doctor were analgesics and antibiotics. In 12% of cases, the doctor recommended that the ship change course significantly in order to discharge the patient to medical care. In another 11% of cases the patient was discharged at an unscheduled but nearby port, although not all of these diversions were urgent. CONCLUSIONS: Despite the difficulties in assessing a patient one cannot see, most illnesses can be diagnosed with a reasonable degree of certainty and useful treatment can be instituted aboard ship. Improving communication systems make the task easier, but variation in the contents of the pharmaceutical cabinets aboard ships is a problem. PMID- 1745170 TI - Murray Griffin and his Changi clinical paintings. PMID- 1745171 TI - The Order of Saint Lazarus of Jerusalem. PMID- 1745172 TI - Stains on the caring mantle. Doctors in aboriginal Australia have a history. AB - Doctors new to Aboriginal Australia are not infrequently surprised that their choice to work with the needy and underprivileged is not cause for unconditional positive regard. The naivete of this position reflects the assumption that the nature of medical work somehow separates doctors from other less caring Europeans who have intruded into Aboriginal Australia. In this paper the ambivalence with which medical professionals are viewed by Aborigines is explored through an examination of particular historical instances drawn from northern Australia, particularly the Kimberley region of Western Australia. It may be that a willingness to interrogate preconceived notions of privileged access will be in the best interests of the profession, and of doctors choosing to work in Aboriginal Australia. PMID- 1745173 TI - Doctors and opera. PMID- 1745174 TI - Nineteenth century masters of general practice. PMID- 1745175 TI - Male homosexuality. PMID- 1745176 TI - Tour of duty: studying tropical diseases in Thailand. PMID- 1745177 TI - Developments in surgical oncology--past, present, and future trends. AB - The historical development of integrated treatment programs for locally advanced or aggressive cancers, for which the results of surgical excision or radiotherapy are unsatisfactory, is reviewed. Chemotherapy should be used first (induction chemotherapy), while tumour vasculature is intact; intra-arterial infusion gives a greater regional effect. Central residual tumour may be eradicated by subsequent radiotherapy and/or surgery. Regional induction chemotherapy is particularly useful in treating locally advanced stage III breast cancer, locally advanced head and neck cancer, gastric cancer, and locally advanced sarcomas and melanomas of the limbs. A team approach, involving surgical and medical oncologists, radiotherapists, immunologists, and others should improve the results in these patients. PMID- 1745178 TI - Operation Habitat. Humanitarian aid to the Kurdish refugees in northern Iraq. PMID- 1745179 TI - The Royal Commission into Aboriginal Deaths in Custody. Aspects of medical interest. AB - The Royal Commission into Aboriginal Deaths in Custody was established in a climate of deep suspicion about the treatment of Aboriginal detainees in Australian prisons and police lock-ups. Three and a half years of exhaustive enquiry have resulted in a mammoth report which not only deals with the problems in the criminal justice system that contribute to these deaths but also discusses in detail the current state of Aboriginal society in Australia. It is the Commission's view that improvements in the lives of Aboriginal people will only occur if they are given the power to bring about those improvements themselves. The Commission's report inevitably has much to say about health matters. This review concentrates on these health matters as they affect Aboriginal people generally, and more specifically, after they arrive within the criminal justice system. The Commission's views about the medical aspects of the investigations of the deaths once they occurred are also summarised as are some of the issues which are at the root of why Aboriginal people are grossly over-represented in custody. PMID- 1745180 TI - Newborn screening in Australia and New Zealand 1984-1990. Human Genetics Society of Australasia/Australian College of Paediatrics Committee on Newborn Metabolic Screening. PMID- 1745181 TI - Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity. AB - OBJECTIVE: A case of severe acute peripheral arterial insufficiency secondary to ergotamine toxicity treated successfully with intravenously administered prostaglandin is presented to highlight the features of this condition and to demonstrate the efficacy of treatment with prostaglandin infusion. CLINICAL FEATURES: A 35-year-old unemployed Caucasian woman with a background of polypharmacy abuse and recurrent migraines presented to St Vincent's Hospital Emergency Department with limb-threatening ischaemia of both legs secondary to chronic ergotamine overuse. INTERVENTION AND OUTCOME: A prostaglandin infusion was started and a dramatic and rapid improvement of her peripheral circulation occurred within six hours. CONCLUSION: Ergotamine toxicity is an uncommon but well documented cause of peripheral vascular insufficiency that should be recognised and treated aggressively because its sequelae can be disastrous. Intravenously administered prostaglandin proved to be successful in this case and is a logical choice as first-line therapy for ergotamine toxicity. PMID- 1745182 TI - A surgeon on the Kokoda Trail. PMID- 1745184 TI - Inflammatory terminology. PMID- 1745185 TI - Three months in a hothouse. PMID- 1745186 TI - Optimisation of respiratory function. AB - OBJECTIVE: To apply pathophysiological principles in the management of patients with acute and chronic respiratory impairment. CONCLUSIONS: Knowledge of the pathophysiology of respiratory disorders is a key element in treatment of patients with impending or established respiratory failure. Therapies to improve and support abnormal gas exchange will minimise the complications of hypoxia and interventions to optimise ventilation and work of breathing may obviate the need for mechanical ventilation. PMID- 1745187 TI - The battle of the couches and the rats. PMID- 1745188 TI - Psychotherapy: from Freud to cognitive science. AB - A change in paradigm has occurred in psychotherapy. Dynamic psychotherapy has still not been shown to be better than placebo treatment or good clinical care. As harm can occur, patients should enter such therapy with caution. The cognitive behaviour therapies are newer and more efficient. They have been demonstrated to be better than placebo or good clinical care for anxiety and depression, and are of benefit in many less common disorders. Informative clinical trials are identified. Clinicians who treat patients with mental disorders should acquaint themselves with these techniques. PMID- 1745189 TI - Hepatic artery cytotoxic perfusion therapy after cryotherapy: a single patient control trial? PMID- 1745190 TI - Malignant Munchausen's. PMID- 1745191 TI - Sea snake envenomation. PMID- 1745192 TI - Taipan envenomation. PMID- 1745193 TI - Anaphylactoid reactions and vitamin K. PMID- 1745194 TI - Cardiac risk factor management. PMID- 1745195 TI - Danazol-carbamazepine interaction. PMID- 1745196 TI - Can infant death from child abuse be prevented? PMID- 1745197 TI - Asthma problems with Turbuhalers. PMID- 1745198 TI - Bricanyl overdose. PMID- 1745199 TI - Household electric shocks. PMID- 1745200 TI - Thrush in the ducts? PMID- 1745201 TI - Exposure to high tension power lines and childhood leukaemia. PMID- 1745202 TI - Pseudomonas fluorescens pseudobacteraemia. PMID- 1745203 TI - Pleurectomy for mesothelioma. PMID- 1745204 TI - Potential focus of fetuses unprotected against rubella. PMID- 1745205 TI - The war against drugs. PMID- 1745206 TI - Anesthesia and chronic hypertension. PMID- 1745207 TI - Cutaneous reactions to drugs. PMID- 1745208 TI - Treatment of the fetus in utero. PMID- 1745209 TI - Surfactant and surfactant replacement. PMID- 1745210 TI - Incidence of pulmonary embolism in total knee arthroplasty. AB - The end-tidal carbon dioxide concentration (ETCO2) of 47 patients undergoing prosthetic knee operations was monitored to detect pulmonary embolism during the anthroplasties. The ETCO2 of one patient dropped suddenly following the release of the tourniquet and insertion of the bone cement. Intracardiac aspiration did not reveal any air. At autopsy there was massive pulmonary thromboembolism and the deep veins of the right leg contained old formed thrombi. Patients undergoing such procedures should be investigated to exclude the presence of deep vein thrombosis so that measures to prevent pulmonary thromboembolism must be taken well in advance. As regards the occurrence of air embolism it is believed that insertion of the bone cement is the most important single factor in the prevention of air embolism during knee arthroplasty. PMID- 1745211 TI - Confirmation of correct tracheal intubation by a self-inflating bulb. PMID- 1745212 TI - Diffusion of an innovation: the first public demonstrations of general anesthesia. PMID- 1745213 TI - A taste of the matter. PMID- 1745214 TI - Hazard communication: what is it? PMID- 1745215 TI - Defending the use of laboratory animals. PMID- 1745216 TI - Ham operators respond. PMID- 1745217 TI - Support for vaginal surgery. PMID- 1745218 TI - Pharmacology woes. PMID- 1745219 TI - The failure of ciprofloxacin to prevent the progression of Streptococcus pneumoniae infections to meningitis. PMID- 1745220 TI - Pediatric knee pyarthrosis presenting as a calf abscess. PMID- 1745221 TI - Cancer of prostate metastatic to the skin diagnosed by immunoperoxidase staining. AB - The authors present a case in which the diagnosis of prostate cancer metastatic to the skin was made by skin biopsy with immunoperoxidase stains for prostatic specific antigen and prostatic acid phosphatase. These are tests that should be performed when the location of the primary malignancy is not otherwise evident. PMID- 1745222 TI - The mechanism of extrachromosomal homologous DNA recombination in plant cells. AB - By cotransfecting plasmids carrying particular mutations in the beta glucuronidase (GUS) gene into Nicotiana plumbaginifolia protoplasts and by monitoring the recombination rates using a recently developed transient assay, we were able to obtain insights into the mechanism of extrachromosomal recombination operating in plant cells. An exchange of flanking markers takes place in over 90% of the recombination events. In most of the remaining cases two consecutive, independent single crossover events occur. These events involve the same DNA substrate and lead to two successive exchanges of flanking markers, thus mimicking a presumed double crossover intermediate. A comparison of the outcome of our experiments with the predictions of two recombination models originally proposed for mammalian cells indicates that extrachromosomal recombination in plant cells is best described by the single strand annealing model. According to this model all recombination events result in an exchange of flanking markers. Our results rule out the double strand break repair model which predicts that flanking markers are exchanged in only half of all events. PMID- 1745223 TI - Pathogenesis-related protein 4 is structurally homologous to the carboxy-terminal domains of hevein, Win-1 and Win-2. AB - The extracellular, acidic pathogenesis-related protein, PR-4, was purified to homogeneity from leaves of Nicotiana tabacum infected with tobacco mosaic virus (TMV) and characterized by partial amino acid sequencing. Complementary DNA clones encoding PR-4 were isolated using an oligonucleotide probe based on the sequence of one of the peptides. The deduced PR-4 protein sequence was found to be related to a family of proteins including hevein and Win-1, which have an amino-terminal lectin domain and a carboxy-terminal domain of unknown function. PR-4 is homologous to the carboxy-terminus of these proteins but does not contain the lectin domain. Thus, the organization of the PR-4 family of proteins is similar to that of the plant chitinase family, in that both contain structural subclasses characterized by the presence or absence of an amino-terminal lectin domain. This observation is consistent with the proposal that the DNA encoding the lectin domain may be capable of transposing to form new genes encoding proteins of more complex, multi-domain structure. The expression of PR-4 mRNA was found to increase dramatically in response to TMV infection and the time course of RNA accumulation was similar to that of other PR proteins. PMID- 1745224 TI - Genetic analysis of a mutant class of Physcomitrella patens in which the polarity of gravitropism is reversed. AB - In the moss Physcomitrella patens, single-cell protonemata and multicellular gametophores respond to reorientation relative to the gravity vector by growing negatively gravitropically. A mutant class in which the protonemata, but not the gametophores, respond by growing towards gravity has been identified. In this paper, we describe the isolation of additional mutants of this class. Complementation and segregation ratio analyses were carried out on these mutants, which indicate that a single gene may mutate to switch the polarity of gravitropism. PMID- 1745225 TI - The yeast IMP1 gene is allelic to GAL2. AB - We have found that many laboratory strains of yeast are defective in galactose metabolism owing to a recessive mutation in the previously characterized nuclear gene, IMP1. This defect leads to a requirement for mitochondrial function for growth on, and metabolism of, galactose. Genetic background affects the degree to which cells are defective. In particular, alleles of GAL3 affect the ability to score the Imp phenotype. We have found that in imp1 strains, transcriptional induction of the galactose inducible genes (GAL1, 2, 7 + 10, MEL1) is normal, but galactose transport is reduced in both rho+ and rho0 cells. This phenotype is normally associated with mutations in GAL2, the galactose permease. Although the growth phenotypes of gal2 and imp1 mutants are distinct, we found that the transformation of imp1 rho0 strains with a plasmid containing the GAL2 gene allows these strains to grow on galactose. Initial genetic analyses did not demonstrate linkage between the GAL2 and IMP1 genes owing to the effects of an unlinked gene on the Imp phenotype. By disrupting the GAL2 gene in an Imp+ background, we have shown that IMP1 and GAL2 segregate as tightly linked genes. Based on these data, we believe that imp1 is a partially defective allele of the GAL2 gene. PMID- 1745226 TI - Molecular cloning and nucleotide sequence of the glycogen branching enzyme gene (glgB) from Bacillus stearothermophilus and expression in Escherichia coli and Bacillus subtilis. AB - The structural gene for the Bacillus stearothermophilus glycogen branching enzyme (glgB) was cloned in Escherichia coli. Nucleotide sequence analysis revealed a 1917 nucleotide open reading frame (ORF) encoding a protein with an Mr of 74787 showing extensive similarity to other bacterial branching enzymes, but with a shorter N-terminal region. A second ORF of 951 nucleotides encoding a 36971 Da protein started upstream of the glgB gene. The N-terminus of the ORF2 gene product had similarity to the Alcaligenes eutrophus czcD gene, which is involved in cobalt-zinc-cadmium resistance. The B. stearothermophilus glgB gene was preceded by a sequence with extensive similarity to promoters recognized by Bacillus subtilis RNA polymerase containing sigma factor H (E - sigma H). The glgB promoter was utilized in B. subtilis exclusively in the stationary phase, and only transcribed at low levels in B. subtilis spoOH, indicating that sigma factor H was essential for the expression of the glgB gene in B. subtilis. In an expression vector, the B. stearothermophilus glgB gene directed the synthesis of a thermostable branching enzyme in E. coli as well as in B. subtilis, with optimal branching activity at 53 degrees C. PMID- 1745227 TI - Growth phase-dependent modification of RNA polymerase in Escherichia coli. AB - During the transition of Escherichia coli cultures from exponential growth to stationary phase, the pre-existing RNA polymerase was found to be converted into at least three different holoenzyme forms, which could be separated by phosphocellulose column chromatography. The relative levels of these three holoenzyme forms changed depending on the phase of cell growth. The altered stationary phase forms of RNA polymerase showed promoter recognition properties that were different from those of the holoenzyme from exponentially growing cells. Enzyme reconstitution experiments showed that the altered promoter selectivity was due to modification of the core enzyme. We propose that modulation of RNA polymerase plays a role in the global switch of gene expression during the transition from exponential growth to stationary phase. PMID- 1745228 TI - Association of cytochrome b translational activator proteins with the mitochondrial membrane: implications for cytochrome b expression in yeast. AB - The products of the nuclear genes CBS1 and CBS2 are both required for translational activation of mitochondrial apocytochrome b in yeast. We report the intramitochondrial localization of both proteins by use of specific antisera. Based on its solubilization properties the CBS1 protein is presumed to be a component of the mitochondrial membrane; the detergent concentrations needed to release CBS1 from mitochondria are almost the same as for cytochrome c1. In contrast, CBS2 behaves like a soluble protein, with some characteristics of a membrane-associated protein. A model is presented for translational activation of cytochrome b, which might also be applicable to translational regulation of other mitochondrial genes. PMID- 1745229 TI - Concurrent transcription from the gid and mioC promoters activates replication of an Escherichia coli minichromosome. AB - The origin of replication of the Escherichia coli chromosome (oriC) is located in an intercistronic region between the gidA and the mioC genes. The possibility that transcription from the promoters of these two genes is involved in minichromosome replication was examined. Inactivation of the gid promoter led to a reduction in transformation frequency with an oriC plasmid but inactivation of the mioC promoter did not. The decrease in transformation frequency was most pronounced when both promoters were inactive. Under conditions that selected for plasmid-harboring cells, mutation of the gid promoter caused efficient multimerization or integration of oriC plasmids into the chromosomal oriC region and loss of free plasmid molecules. These changes in plasmid structure were also observed, albeit less frequently, with some plasmids defective in mioC promoter activity. In an in vitro DNA replication system for oriC DNA, plasmids with a defective gid promoter had greatly reduced template activity and essentially no replication occurred when both promoters were inactive. These results suggest that coupled transcription starting from the gid as well as the mioC promoter activates initiation of plasmid replication, the major contribution being made by gid transcription. These two promoters are suggested to be under stringent control. PMID- 1745230 TI - Homologous recombination between plasmid DNA molecules in maize protoplasts. AB - The requirements for homologous recombination between plasmid DNA molecules have been studied using the PEG (polyethylene glycol)-mediated transformation system of maize (Zea mays L.) protoplasts coupled with the transient expression assay for beta-glucuronidase (GUS). Two plasmids were introduced into maize protoplasts; one plasmid (pB x 26) contained a genomic clone of the Adh1 maize gene; the other plasmid (piGUS) was a promoterless construction containing part of intron A of the Adh1 gene fused to the gusA coding sequence. Thus, the two vectors shared an effective homologous region consisting of a 459 bp (HindIII PvuII) fragment of the Adh1 intron A sequence. An active gusA fusion gene would result upon homologous recombination between the plasmids within the intron A sequence, and indeed GUS activity was observed in extracts following co transformation of maize protoplasts with the two plasmids. The presence of recombinant DNA molecules in protoplast DNA isolated 1 day after co transformation was verified using polymerase chain reactions (PCR) and Southern blots. For efficient homologous recombination, both plasmids had to be linearized. The recombination reaction was induced by restriction of the plasmid molecules either inside the effective homologous region or at the borders of the intron sequence. However, the presence of even small, terminal, nonhomologous sequences at the 3' end of the pB x 26 fragment inhibited the recombination reaction. Also, both ends of the linearized piGUS DNA molecules were involved in the recombination reaction. The results revealed some features of homologous recombination reactions occurring in plant cells which cannot be accommodated by mechanisms postulated for similar reactions in animal system and in lower eukaryotes. PMID- 1745231 TI - Investigation of cis-acting sequences regulating expression of the gene encoding yolk protein 3 in Drosophila melanogaster. AB - The regulatory sequences leading to the ovarian and fat body expression of yolk proteins 1 and 2 (YP1 and 2) of Drosophila melanogaster have been characterised in some detail. These genes (yp1 and yp2) share many enhancer elements, and some important regulatory sequences lie within the coding regions. We have begun to investigate the cis-regulation of the gene encoding yolk protein 3 (yp3). We describe a system for P element transformation using the complete and unaltered yp3 gene rather than reporter genes and describe sequences conferring correct expression in the ovary and carcass. PMID- 1745232 TI - TFS1: a suppressor of cdc25 mutations in Saccharomyces cerevisiae. AB - The TFS1 gene of Saccharomyces cerevisiae is a dosage-dependent suppressor of cdc25 mutations. Overexpression of TFS1 does not alleviate defects of temperature sensitive adenylyl cyclase (cdc35) or ras2 disruption mutations. The ability of TFS1 to suppress cdc25 is allele specific: the temperature-sensitive cdc25-1 mutation is suppressed efficiently but the cdc25-5 mutation and two disruption mutations are only partially suppressed. TFS1 maps to a previously undefined locus on chromosome XII between RDN1 and CDC42. The DNA sequence of TFS1 contains a single long open reading frame encoding a 219 amino acid polypeptide that is similar in sequence to two mammalian brain proteins. Insertion and deletion mutations in TFS1 are haploviable, indicating that TFS1 is not essential for growth. PMID- 1745233 TI - Highly bioluminescent Bacillus subtilis obtained through high-level expression of a luxAB fusion gene. AB - Bioluminescence levels comparable to those achievable in Escherichia coli have yet to be obtained from luxAB expression in gram-positive bacteria. In this communication we describe the gene engineering required to generate a highly bioluminescent derivative of Bacillus subtilis. The combination of a powerful promoter, Pxyn, a fusion derivative of luxAB from Vibrio harveyi and translational coupling have overcome the previously reported limitations in luxAB expression. The implications for highly bioluminescent gram-positive organisms are discussed. PMID- 1745234 TI - Comparison of the sequences of the nagE operons from Klebsiella pneumoniae and Escherichia coli K12: enhanced variability of the enzyme IIN-acetylglucosamine in regions connecting functional domains. AB - The nagE operon, encoding the enzyme II specific for N-acetylglucosamine (EIINag), and adjacent DNA from the chromosome of Klebsiella pneumoniae were sequenced and compared with the corresponding sequence from Escherichia coli K12. The deduced EIINag sequences differ in 72 out of 651 amino acids, the K. pneumoniae sequence being three residues longer. The amino acid differences were distributed unevenly, and were most frequent in regions connecting the three functional domains of the protein. In the nagE-nagB intergenic region, two promoter, two operator, and one CAP consensus sequence with regulatory functions were highly conserved. The nag structural genes from both species were very similar (83% DNA similarity; 89% amino acid similarity) except for frequent AT to GC exchanges in the wobble base of codons in K. pneumoniae DNA relative to the E. coli DNA. PMID- 1745235 TI - Nuclear migration in Saccharomyces cerevisiae is controlled by the highly repetitive 313 kDa NUM1 protein. AB - We have isolated a novel gene (NUM1) with unusual internal periodicity. The NUM1 gene encodes a 313 kDa protein with a potential Ca2+ binding site and a central domain containing 12 almost identical tandem repeats of a 64 amino acid polypeptide. num1-disrupted strains grow normally, but contain many budded cells with two nuclei in the mother cell instead of a single nucleus at the bud neck, while all unbudded cells are uninucleate. This indicates that most G2 nuclei divide in the mother before migrating to the neck, followed by the migration of one of the two daughter nuclei into the bud. Furthermore, haploid num1 strains tend to diploidize during mitosis, and homozygous num1 diploid or tetraploid cells sporulate to form many budded asci with up to eight haploid or diploid spores, respectively, indicating that meiosis starts before nuclear redistribution and cytokinesis. Our data suggest that the NUM1 protein is involved in the interaction of the G2 nucleus with the bud neck. PMID- 1745236 TI - Carbon-starvation induction of the ugp operon, encoding the binding protein dependent sn-glycerol-3-phosphate transport system in Escherichia coli. AB - The gene products of the ugp operon of Escherichia coli are responsible for the uptake of sn-glycerol-3-phosphate and certain glycerophosphodiesters. The regulation of ugp is mainly phoBR-dependent. Significant expression, however, can be observed even in the presence of high concentrations of phosphate, a condition which normally completely represses pho expression. Pho-independent ugp expression was found to be derepressed during the late logarithmic growth phase due to carbon starvation. Among different carbon sources tested, glucose caused the most complete repression. Addition of cAMP prevented glucose repression, indicating that a cAMP-CRP control mechanism may be directly or indirectly involved in the carbon-starvation response. This conclusion is supported by the fact that pho-independent ugp expression correlated with the presence of the cya and crp gene products. PMID- 1745237 TI - Codon usage in Aspergillus nidulans. AB - Synonymous codon usage in genes from the ascomycete (filamentous) fungus Aspergillus nidulans has been investigated. A total of 45 gene sequences has been analysed. Multivariate statistical analysis has been used to identify a single major trend among genes. At one end of this trend are lowly expressed genes, whereas at the other extreme lie genes known or expected to be highly expressed. The major trend is from nearly random codon usage (in the lowly expressed genes) to codon usage that is highly biased towards a set of 19-20 "optimal" codons. The G + C content of the A. nidulans genome is close to 50%, indicating little overall mutational bias, and so the codon usage of lowly expressed genes is as expected in the absence of selection pressure at silent sites. Most of the optimal codons are C- or G- ending, making highly expressed genes more G + C-rich at silent sites. PMID- 1745238 TI - Characterization of the supervirulent virG gene of the Agrobacterium tumefaciens plasmid pTiBo542. AB - The virG gene of the Agrobacterium tumefaciens Ti plasmid pTiBo542 has previously been reported to elicit stronger vir gene expression than its counterpart in the pTiA6 plasmid, a property we call the "superactivator" phenotype. The DNA sequence of the pTiBo542 virG gene was determined and compared to that of the pTiA6 gene. The DNA sequences of these genes differ at 16 positions: two differences are in the promoter regions, 12 are in the coding regions, and two are in the 3' untranslated regions. The 3' end of the pTiA6 virG gene also contains a probable insertion sequence that is not found downstream of the pTiBo542 gene. The base pair differences, in the two coding regions result in only two amino acid differences, both in the amino-terminal halves of the proteins. Five hybrid virG genes were constructed and used to activate the expression of a virB::lacZ gene fusion. Differences in the coding regions of these genes accounted for most of the superactivator phenotype, while differences at the promoter and 3' untranslated regions also contributed. These findings suggest that the properties of these VirG proteins and their quantities are important for vir gene induction, and also suggest a long-term selective pressure for mutations contributing to differences between these two genes. PMID- 1745239 TI - Isolation of mutants of Arabidopsis thaliana in which accumulation of tobacco mosaic virus coat protein is reduced to low levels. AB - We have found that Arabidopsis thaliana is susceptible to infection with a crucifer strain of tobacco mosaic virus (TMV-Cg); the coat protein of TMV-Cg accumulated to a high level in uninoculated rosette leaves several days after inoculation. As a first step in the search for host-coded factors that are involved in virus multiplication, we isolated mutants of A. thaliana in which the accumulation of TMV-Cg coat protein was reduced to low levels. Of 6000 M2 plants descended from ethyl methanesulfonate-treated seeds, two such lines (PD114 and PD378) were isolated. Genetic analyses suggested that the PD114 phenotype was caused by a single nuclear recessive mutation, and that PD114 and PD378 belonged to the same complementation group. The coat protein accumulation of a tomato strain of TMV (TMV-L) was also reduced in PD114 plants compared to that in the wild-type plants. In contrast, PD114 plants infected with turnip crinkle or turnip yellow mosaic viruses, which belong to taxonomic groups other than Tobamovirus, expressed similar levels of these coat proteins as did infected wild type plants. PMID- 1745240 TI - Molecular analysis of the Escherichia coli hns gene encoding a DNA-binding protein, which preferentially recognizes curved DNA sequences. AB - We previously demonstrated that the E. coli protein, H-NS (or H1a), encoded by the gene hns (or osmZ or bglY) preferentially recognizes curved DNA sequences in vitro. In order to gain further insight into the complex function of H-NS and the significance of DNA curvature, we constructed a structurally defined hns deletion mutant on the E. coli chromosome. The hns deletion mutant thus obtained showed a variety of phenotypes previously for other lesions in hns. It was further demonstrated that, in this hns deletion background, numerous E. coli cellular proteins were either strongly expressed or remarkably repressed, as compared to their expression levels in wild-type cells. PMID- 1745241 TI - Cloning and expression analysis of a potato cDNA that encodes branching enzyme: evidence for co-expression of starch biosynthetic genes. AB - One of the key enzymes involved in the formation of amylopectin, which is the major component of starch, is branching enzyme. A cDNA for potato branching enzyme was cloned by screening a tuber-specific cDNA expression library using an antiserum directed against a denatured preparation of the protein. Complementation of an Escherichia coli strain deficient in branching enzyme was achieved using a construct derived from this clone. Analysis of the expression of the gene in potato revealed a close association with conditions favouring starch biosynthesis. The expression pattern of the gene coding for potato branching enzyme, as analyzed at the mRNA level, closely resembles that of AGPase S, a gene coding for one of the subunits of ADP-glucose pyrophosphorylase, which is the key regulatory enzyme in the starch biosynthetic pathway. This raises the possibility that enzymes involved in the pathway are coordinately regulated at the transcriptional level. PMID- 1745242 TI - Evidence for binding of at least two factors, including T-rich strand-binding factor(s) to the single-stranded ARS1 sequence in Saccharomyces cerevisiae. AB - To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors interacting with the ARS1 region located near the centromere of chromosome IV in Saccharomyces cerevisiae. Using the gel shift assay, we found protein factor(s) which specifically bound to the T-rich strand of the region containing the core consensus and its flanking sequences in ARS1, but not to the opposite strand. We designated this factor ATS (ARS1, T-rich strand-binding factor(s]. Similar specific complexes were also detected with oligonucleotide probes specific for the H4 or C2G1 ARS. As we have previously identified another binding factor, we conclude that at least two factors bind to the single-stranded ARS1 sequence. PMID- 1745243 TI - Targeted disruption of chloroplast genes in Chlamydomonas reinhardtii. AB - We have developed an efficient procedure for the disruption of Chlamydomonas chloroplast genes. Wild-type C. reinhardtii cells were bombarded with microprojectiles coated with a mixture of two plasmids, one encoding selectable, antibiotic-resistance mutations in the 16S ribosomal RNA gene and the other containing either the atpB or rbcL photosynthetic gene inactivated by an insertion of 0.48 kb of yeast DNA in the coding sequence. Antibiotic-resistant transformants were selected under conditions permissive for growth of non photosynthetic mutants. Approximately half of these transformants were initially heteroplasmic for copies of the disrupted atpB or rbcL genes integrated into the recipient chloroplast genome but still retained photosynthetic competence. A small fraction of the transformants (1.1% for atpB; 4.3% for rbcL) were nonphotosynthetic and homoplasmic for the disrupted gene at the time they were isolated. Single cell cloning of the initially heteroplasmic transformants also yielded nonphotosynthetic segregants that were homoplasmic for the disrupted gene. Polypeptide products of the disrupted atpB and rbcL genes could not be detected using immunoblotting techniques. We believe that any nonessential Chlamydomonas chloroplast gene, such as those involved in photosynthesis, should be amenable to gene disruption by cotransformation. The method should prove useful for the introduction of site-specific mutations into chloroplast genes and flanking regulatory sequences with a view to elucidating their function. PMID- 1745244 TI - Specificity of recA441-mediated (tif-1) mutational events. AB - To investigate the impact of SOS induction on the distribution of spontaneous mutation, 111 recA441-mediated mutations were characterized at the DNA sequence level in the lacI gene of Escherichia coli. A 2.6-fold enhancement in lacI- mutation frequency was observed after induction of the SOS system in the absence of mutagenic treatment, and specific classes of mutational events were induced. G:C----C:G, G:C----T:A and A:T----T:A transversion events were specifically enhanced after SOS induction. A preferential 5'-Y-Purine-3' neighbouring base specificity for these transversion events is reported here (normalised for mutation of the purine residue). In addition, a preference for transversion events at 5'-C/GTGG-3' sequences is also observed. Fifty events were recovered at the lacI "frameshift hotspot site" and were equally represented by 4 bp addition and deletion events. This 1:1 ratio deviates significantly from the 4:1 distribution characteristic of spontaneous frameshift mutation in the RecA+ background and is a consequence of the fourfold induction of the (-)4 event. This abberrant distribution was confirmed by oligomeric probing of 474 independent recA441-mediated spontaneous lacI- mutations. PMID- 1745245 TI - Ribosomal protein S14 is not responsible for the Minute phenotype associated with the M(1)7C locus in Drosophila melanogaster. AB - A locus associated with a severe Minute effect has been mapped at 7C on the X chromosome of Drosophila melanogaster. Previous work has suggested that this Minute encodes ribosomal proteins S14A and S14B. We have made a chromosomal deficiency that removes the S14 ribosomal protein genes, yet does not display the Minute phenotype. These data suggest that the S14 genes do not actually correspond to the Minute locus. PMID- 1745246 TI - Alteration of an amino acid residue outside the active site of the ricin A chain reduces its toxicity towards yeast ribosomes. AB - Yeast transformants containing integrated copies of a galactose-regulated, ricin toxin A chain (RTA) expression plasmid were constructed and used in an attempt to isolate RTA-resistant yeast mutants. Analysis of RNA from mutant strains demonstrated that approximately half contained ribosomes that had been partially modified by RTA, although all the strains analysed transcribed full-length RTA RNA. The mutant strains could have mutations in yeast genes giving rise to RTA resistant ribosomes or they could contain alterations within the RTA-encoding DNA causing production of mutant toxin. Ribosomes isolated from mutant strains were shown to be susceptible to RTA modification in vitro suggesting that the strains contain alterations in RTA. This paper describes the detailed analysis of one mutant strain which has a point mutation that changes serine 203 to asparagine in RTA protein. Although serine 203 lies outside the proposed active site of RTA its alteration leads to the production of RTA protein with a greatly reduced level of ribosome modifying activity. This decrease in activity apparently allows yeast cells to survive expression of RTA as only a proportion of the ribosomes become modified. We demonstrate that the mutant RTA preferentially modifies 26S rRNA in free 60S subunits and has lower catalytic activity compared with native RTA when produced in Escherichia coli. Such mutations provide a valuable means of identifying residues important in RTA catalysis and of further understanding the precise mechanism of action of RTA. PMID- 1745247 TI - Genetic and biochemical characterization of little isoxanthopterin (lix), a gene controlling dihydropterin oxidase activity in Drosophila melanogaster. AB - Dihydropterin oxidase catalyses the oxidation of 7,8-dihydropteridines into their fully oxidized products, and is involved in the biosynthesis of isoxanthopterin. Fifteen Drosophila melanogaster mutants, selected for their low pterin and isoxanthopterin content, were assayed for dihydropterin oxidase activity. The activity was around 100% in most mutants tested, slightly reduced in red, g and dke, and undetectable in lix. In flies carrying various doses of the lix+ allele, a correlation was found between enzyme activity and the number of lix+ copies in the genome. The results suggest that lix is the structural gene for the dihydropterin oxidase enzyme. Isoxanthopterin was quantitated in strains carrying deficiencies for the region in which lix has been mapped by recombination. This allowed us to assign the lix locus to the 7D10-7F1-2 segment of the X chromosome. PMID- 1745248 TI - [Effect of intermittent catheterization on urinary tract infections and incontinence in children with spina bifida]. AB - Although the primary objective of clean intermittent (self) catheterization (CIC) was to regain continence in (older) children with myelomeningocele (MMC), we used the method also in the very young with detrusor-sphincter dyssynergia, to prevent future damage from the combined effects of obstruction and urinary tract infection (UTI). The results, in terms of incidence of UTI and degree of incontinence before and during CIC, were assessed in 61 children with MMC who had started CIC between 1985 and 1988. Mean follow up was 45.3 +/- 27.3 months, mean age at the start of CIC was 6.9 +/- 4.6 years. The incidence of UTI during CIC proved significantly lower than before CIC (chi 2 = 20.92, p less than 0.001), and the improvement in incontinence was also statistically significant (chi 2 = 45.16, p less than 0.001). In children with MMC, CIC seems ideally suited to prevent damage to the kidneys from the life-long problem of recurrent UTI's. It will also help in preventing bladder wall fibrosis--an important cause of loss of detrusor compliance--secondary to repeated UTIs. PMID- 1745249 TI - [Occupational training measures for adolescents with asthma and allergy: one-year vocational education]. AB - The "Forderungslehrgang" in our asthma center is a special training program for adolescents handicapped by asthma or allergic diseases who are therefore not able to start apprenticeship. The course takes one year. Besides vocational guidance and tryout of different occupations, medical and psychological diagnostics are performed. Medical service is provided all day, and a hospital with emergency unit is within the area. Though 41% of the participants did finish school without any qualified graduation after their compulsory school attendance, 79% were able to start apprenticeship after the course. PMID- 1745250 TI - [Atypical pathogen spectrum in community-acquired infections of the lower respiratory tract in childhood]. AB - Over a period of 14 months, we obtained nasal and throat swabs for virological examinations from patients, admitted to hospital with suspected pneumonia. Fifty five cases of perihilar bronchitis and 103 cases of pneumonia were diagnosed based on radiological criteria. In 36% (n = 57) of the children, a pathogen could be determined by antigen ELISA. We found the following spectrum: Respiratory syncytial virus: 42%; Influenza A: 8%; Influenza B: 10%; Parainfluenza 1: 3%; Parainfluenza 2: 10%; Parainfluenza 3: 2%; Chlamydia: 17%; and Mycoplasma pneumoniae (serology only): 7%. In a control group of 59 healthy children, only one child showed a pathogen. In the past, viruses and Chlamydia have been underestimated as causes of lower respiratory tract infections. Antigen determination by ELISA has proved to be a reliable and rapid method for their detection. PMID- 1745251 TI - [Evaluation of the bilirubinometer Hico-Bilimat A 700]. AB - The Hico-Bilimeter A 700 is a simple filter photometer for the determination of total bilirubin in neonatal serum, reading the absorbance of the undiluted sample at two wavelengths. Precision of the measurements is good, with linearity acceptable up to a concentration of 18 mg/dl. Compared to the values obtained with the reference method the results below 18 mg/dl are 16% too high on average; above 18 mg/dl the scatter of results is markedly increased. Even a moderate hemolysis shows a distinct influence on the measurements. Using the instrument tested no reliable results could be obtained, especially in hemolytic samples. PMID- 1745252 TI - [Therapy of hyperammonemia in carbamyl phosphate synthase deficiency with peritoneal dialysis and venovenous hemofiltration]. AB - Inborn errors of metabolism with hyperammonaemia cause emergency situations with unconsciousness, convulsion, hyperpnoea and hyperpyrexia. Therefore hyperammonaemia has to be treated immediately after diagnosis to avoid irreversible damage. Two newborns with carbamylphosphates synthetase deficiency are described. Both, continuous peritoneal dialysis and venovenous haemofiltration have proved to be effective methods to reduce serum ammonia concentration to values of less than 300 mu/l. Because of the severity of the enzyme defect in both cases, (carbamylphosphate synthetase was not detectable in liver tissue), treatment finally had to be stopped, and both patients died. PMID- 1745253 TI - [Clinical aspects and allergy-immunologic parameters in 40 children 0-7 years of age with atopic dermatitis]. AB - Forty children with atopic dermatitis were evaluated for history, clinical features and allergologic-immunologic parameters. Lichenoid skin lesions were found in 67.5%, follicular lesions in 57.5%, and eczematoid lesions in 50% in children. 25% of children suffered from associated food allergy, 15% from respiratory atopy, and 5% from contact urticaria. The diagnostic efficiency to show specific sensitization was 93% for Pediatric Phadiatop, 90% for Food Multidisc (fx5 Pharmacia), 88% for skin tests (Prick), 73% for elevated total serum IgE, 65% for Phadiatop, and 60% for family history. The classification of atopic dermatitis into an extrinsic type with specific sensitizations to allergens and into an intrinsic type without specific sensitizations appears to be useful because specific sensitizations significantly correlate with severer skin condition and disease course. PMID- 1745254 TI - [Hallervorden-Spatz syndrome. Indicative findings in cranial computerized and magnetic resonance tomography for intra vitam diagnosis]. AB - We report the case of a female patient with a progressive therapy-resistant extrapyramidal movement disorder. Cranial computed tomography showed symetrical hyperdensities in the globus pallidus. The same areas are of decreased signal intensity in magnetic resonance imaging. These findings suggest an increased iron accumulation. The clinical symptoms and the radiological findings of the cerebrum are highly indicative for a Hallervorden-Spatz disease. PMID- 1745255 TI - [Laryngeal atresia in an infant with chondrodysplasia punctata, rhizomelic type]. AB - Laryngeal atresia had to be unexpectedly detected and treated in a newborn baby. The outer appearance with symmetric shortening of humeri and femora and radiological features with epiphysial and extraepiphysial calcifications led to the diagnosis of rhizomelic chondrodysplasia punctata. This disease is described as a peroxisomal disorder with a poor prognosis on the basis of pathophysiological and diagnostic features. PMID- 1745256 TI - [Cystic space occupying lesion of the upper pole of the kidney in a newborn infant. Case report and differential diagnosis]. AB - In a newborn female infant a cystic lesion in the upper pole of the right kidney was detected by sonography 4 weeks before an uneventful delivery. In the postnatal period the sonographic examination, IVP, CT, and the biochemical data as well were not able to classify definitely this lesion as a benign cyst, adrenal hemorrhage or cystic malignoma. Therefore a laparatomy was performed, which revealed a cystic neuroblastoma. PMID- 1745257 TI - [Linear IgA dermatosis in childhood]. AB - In a six-year-old girl with linear IgA dermatosis of childhood there were lesions with typical rosette like configuration, crusted erosions and isolated bullae on apparently normal skin. The histopathology revealed subepidermal blister and superficial perivascular lymphohistiocytic infiltrate with many neurophils and some eosinophils. Direct immunofluorescence examination showed linear deposits of IgA along the basal membrane zone. Circulating antibodies were absent. Therapy with dapsone in a dose of 25 mg/day was effective. PMID- 1745258 TI - [Risk of recurrent seizures after the first afebrile grand mal seizure in childhood]. AB - A cohort of 74 children three months to 16 years-old who presented with a first unprovoked seizure were followed for five years to assess the risk of recurrence. Children with febrile convulsions, immediate posttraumatic seizures, meningitis and encephalitis were not included. The risk of recurrence was 68% for a second seizure. 47% of the patients developed an epilepsy. 85% of recurrences occurred within the first 6 months and 100% within 2 1/2 years. A history of epilepsy in a first degree relative, age at first seizure, duration of seizure, initial EEG or neurologic status were not associated with significantly higher risk of recurrence. PMID- 1745259 TI - [Toxicity of mercury in dental amalgam fillings]. PMID- 1745260 TI - [Features of the interaction of Escherichia coli and Francisella tularensis RNA polymerases with hybrid plasmids bearing fragments of Francisella tularensis chromosomal DNA]. AB - Hybrid plasmids containing the fragments of Francisella tularensis chromosomal DNA and capable of tet-gene expression both in Escherichia coli and Francisella tularensis cells were constructed. The regions of francisella chromosomal DNA binding the RNA-polymerases of Escherichia coli and Francisella tularensis were found by the electron microscopy technique. Interconnection of those regions with the expression of tet-gene of the hybrid plasmids was demonstrated. PMID- 1745261 TI - [Biochemical, antigenic and protective properties of the outer membrane of tularemia pathogens]. AB - The outer membranes of Francisella tularensis were studied. The membranes were identified morphologically, immunologically and biochemically. They contained 12 20% of protein, 15-30% of carbohydrates, up to 40% of lipids. The main integral proteins of the outer membranes were the 47, 43, 17 and 12 kD proteins. The main protein 63 kD was not integral. The lipopolysaccharides isolated from the outer membranes and acetone-dried cells did not possess the protective properties in experimental tularemia. The preparations of outer membranes possessed the protective properties for mice infected with the virulent strain 503. Chitosan amplified the protective properties of outer membranes. PMID- 1745262 TI - [Determination of the initial rate of antimutagenic repair in UV-irradiated WP2 Escherichia coli cells]. AB - The initial rates of antimutagenic dark repair were measured in Escherichia coli WP2 trpE65 cells irradiated by UV-light (11 J/m2) and then incubated in liquid media of various compositions. Samples were taken from suspension of incubated bacteria every 5 min following irradiation, mixed with acriflavine to block further repair and plated onto the selective medium containing acriflavine (1 micrograms/ml) to score the Trp+ mutations. The initial rate of antimutagenic repair was estimated from the kinetics of disappearance of mutations in several successive probes. It appeared to depend on the composition of a medium, to establish just after placing irradiated bacteria onto the medium and to decrease significantly in irradiated cells incubated under conditions favourable for growth. The decrease was not due to inhibition of postreplicative repair and was not caused by casaminoacids as such, but by combination of growth factors that provided the intensive protein synthesis. The decrease could be responsible for a strong mutational response of bacteria to irradiation because it secures the survival of premutagenic lesions in DNA till mutation fixation. It is suggested that metabolic regulation of the antimutagenic repair activity exists, based on an active switch of the energy flows required for several parallel metabolic pathways that proceed in irradiated cells. PMID- 1745263 TI - [Subcloning and study of the GTP-cyclohydrolase gene of Bacillus subtilis]. AB - Bacillus subtilis GTP-cyclohydrolase gene and its deletion derivatives were subcloned in Escherichia coli cells. The position of the gene within the riboflavine operon was defined. The deletion of the 14 kDa fragment from the N end of GTP-cyclohydrolase gene did not affect the enzyme activity. PMID- 1745264 TI - [Cloning and inactivation of a chromosomal copy of the imidazole glycerophosphate dehydratase (HIS) gene from Hansenula polymorpha]. AB - A gene for imidazole glycerophosphate dehydratase (HIS) has been selected from the library of Hansenula polymorpha genes by complementation of Escherichia coli hisB mutations or his3 mutation of Saccharomyces cerevisiae. Inactivation of the gene in Hansenula polymorpha strain 48V, as well as Leu(-)-Leu+ conversion of phenotype and arising of antibiotic G418 resistance resulted from transformation of the strain by the linear DNA molecules of the cloned HIS-gene with the in vitro inserted LEU2 gene from Saccharomices cerevisiae and KmR gene. The Southern hybridization analysis of the Leuf+His- G418R clones representing 1-2% of transformants population together with the DNA analysis of the monospore clones from the hybrid Leu+His-G418R transformant tetrad and tester strain have revealed the locus specific nature of the clones. PMID- 1745265 TI - [Sensitizing properties of Brucella protein antigens synthesized in K12 Escherichia coli cells]. AB - The sensitizing properties of brucella 31 kD and 31+15 kD protein antigens produced by Escherichia coli cell carrying and expressing the corresponding brucella genes were compared. In experiments evaluating the test of mouse feet oedema in CBA line animals the property of the 31 kD antigen preparation to induce the specific oedema effect was demonstrated on the level comparable with the one produced by the brucella outer membrane proteins preparation. The obtained data were confirmed in the experiments on adoptive transfer of prolonged type hypersensitivity via the spleen cells from the sensitized donors to intact recipient animals. The future of molecular cloning technique usage for obtaining the homogeneous stable preparations of brucella antigens with low reactivity and high specificity is discussed. PMID- 1745266 TI - [Diaminopimelate pathway for lysine synthesis in Escherichia coli and bacilli]. AB - The diaminopimmelate (DAP) pathway for lysine biosynthesis in Escherichia coli and some species of Bacillus are presented in the review. It was shown that the major variations of the DAP pathway of Bacillus subtilis from that described and extensively studied in Escherichia coli exist. PMID- 1745267 TI - [Saccharomyces cerevisiae mutants with increased mitotic stability of plasmids isolated during long-term culturing of transformants under selective conditions]. AB - Analysis of the plasmid containing clones of transformants of Saccharomyces cerevisiae in the population cultivated under the nonselective conditions has shown their vast heterogeneity in the mitotic stability of the plasmids Yep13 and Yep91. For instance, the clones were obtained with the different types of the hereditary plasmid stabilization: integration with the chromosome and genotype or plasmid mutations increasing the vector copy number. The increased expression level was registered in the mutants for the heterologous genes AmpR of Escherichia coli and HBsAg of hepatitis B. The clones were found with the considerably varying mitotic stability of the plasmids of the modification type variability, the latter expressing the fluctuations of plasmid copy number at the change of cultivation conditions. PMID- 1745268 TI - [Analysis of deletion mutations of the dystrophin gene by the multiplex polymerase chain reaction method in the diagnosis of Duchenne muscular dystrophy]. AB - The 33 patients suffering from the Duchenne muscular dystrophy (DMD), 7 healthy donors and a DMD risk family were studied by means of polymerase multiplex chain reaction (MPCR) with 6 oligoprimer pairs for 6 different exons of dystrophin gene. The deletions varying in sizes from 1 to 6 exons were detected in 12 out of 33 DMD patients studied (36.3%). The prenatal diagnosis of DMD was carried out by chorionic villus biopsy on the 1st trimester of pregnancy. Contrary to earlier findings, in elder brother with sever DMD manifestation, no visible deletion was detected in the DNA sample from the male foetus and thus the diagnosis of DMD in foetus was rejected. The perspectives of MPCR in pre and postnatal diagnosis of DMD are discussed. PMID- 1745269 TI - [Mobilization transfer of the pUB110 plasmid between gram-positive bacteria]. AB - The three factor crosses between the donor strain Bacillus subtilis 168 harbouring the plasmid pUB102-4, Bacillus thuringiensis strain carrying the mobilizing plasmid pAM beta 1 and recipient strain Lactobacillus fermenti were conducted in order to elaborate the optimal conditions of the plasmid pUB102-4 mobilization for transfer into gram-positive microorganisms and to elucidate the possible expression of endogluconase genes in a lactobacillus strain. The Lactobacillus fermenti transconjugants carrying the pUB102-4 plasmid were obtained in the three factor reciprocal crosses with the streptococcus recipient strain and Bacillus subtilis recipients. The presence of the plasmids in transconjugants was confirmed by colony hybridization with the [32P]-labelled plasmid DNA and KMC-ase activity in transconjugant cells. The proposed system of crosses using the high copy number plasmid derivatives of pUB110 mobilized with high frequency by the pAM beta 1 plasmid demonstrates the possibility to increase the circle of gram-positive host bacteria avoiding time and labour consuming operations. PMID- 1745270 TI - [Behavior of Sa plasmid in tularemia pathogen cells]. AB - The genome of Sa plasmid is shown to be a subject of genetical rearrangements in Francisella tularensis cells. The rearrangements either result in plasmid integration into the host cell genome or intramolecular amplification of cat-gene with the subsequent excision and recombination of the derivative plasmids. Stable inheritance of the plasmid is registered after integration while plasmid elimination occurs in case of extrachromosomal localisation. PMID- 1745271 TI - [Study of CAT gene expression in Sa and pC194 plasmids in Escherichia coli, Francisella tularensis, and Bacillus subtilis cells]. AB - The unit activities were defined for chloramphenicol-acetyltransferases coded for by the cat-genes of the plasmids Sa and pC194 in Francisella tularensis, Escherichia coli and Bacillus subtilis cells. Francisella tularensis cells were shown to hold intermediate position between Escherichia coli and Bacillus subtilis cells in their ability to express the genes of the different taxonomic origin. The direct dependence was found between the dose of the gene coding for chloramphenicol-acetyltransferase synthesis and efficiency of the gene expression, minimal inhibiting concentration of the antibiotic and colony size on the media containing chloramphenicol. PMID- 1745272 TI - [Transfer of bacteriophage PRD1 genes into modified plasmid Sa of Escherichia coli and Francisella tularensis cells]. AB - The donor specific bacteriophage PRDI has been shown to mediate the genes transfer into Escherichia coli and Francisella tularensis cell under certain conditions. It is necessary for the process that the recipient cells inherit the plasmids determining absorbtion of bacteriophages on the cellular surface while the transferred genes are able to be expressed. The frequencies of the tet-gene transfer from the plasmid pSKFT5 into Escherichia coli and Francisella tularensis 15 cells inheriting the plasmid Sa are, correspondingly, 10(-6) and 10(-7) clones per bacteriophage plaque. PMID- 1745273 TI - [A simple method of purifying staphylococcal alpha-toxin and a study of its properties]. AB - The simple method is proposed for isolation and purification of staphylococcal alpha-toxin that permits one to obtain the homogeneous toxic protein with high activity. The time necessary for maximal toxin production at cultivation has been defined. The thermostability and interferonogenic characteristics of the obtained alpha-toxin were studied. PMID- 1745274 TI - [Synthesis of the E-antigen of the hepatitis B virus (HBeAg) in eukaryotic cells by a recombinant strain of the vaccinia virus]. AB - The recombinant plasmids containing the gene for hepatitis B viral core-antigen with the pre-core-sequence controlled by the early-late promoter of the 7.5' K protein gene were constructed. The recombinant strains of vaccinia virus were obtained on their basis (vHBe42-1 and vHBe42-3) selectively expressing HBeAg of hepatitis B virus. The kinetics of HBeAg synthesis was studied in infected cells as well as secretion of the protein into culturing medium. Three proteins were found by blotting technique in the cells infected by vHBe42-3 that react with the specific antiserum to HBeAg and have the mol. masses 25, 22 and 17 kD. The completely processed HBeAg 17 kD was found in the culturing medium. The rabbit serums from the animals immunized by recombinant vHBe42-3 contained antibodies to HBeAg but not to HBcAg. This makes it possible to study the structural and functional organization, immunological properties and role of this antigen in pathogenesis of hepatitis virus B and to construct the specific test systems for screening HBeAg and corresponding antibodies. PMID- 1745275 TI - [Characteristics of the R-plasmid pM3 (IncP-9) of a broad circle of hosts]. AB - A new broad host range plasmid pM3 (IncP-9) was found in a facultative methylotrophic bacteria Pseudomonas putida and described. The pM3 plasmid is characterized by thermo-instability in Enterobacteriaceae family of bacteria at 36 degrees C or higher temperatures. It is also unable to be inherited as an autonomous element in the obligate methylotrophic bacteria Methylobacillus M75. The peculiarities of plasmid inheritance make possible to use it as a tool for genetic research, for instance, to construct the donor strains in Methylobacillus M75 able to mobilize the chromosomal genes for conjugational transfer in isogenic systems of crosses. PMID- 1745276 TI - AAEM minimonograph #37: facial and limb myokymia. AB - Myokymia is a clinical phenomenon associated with characteristic electromyographic activity referred to as myokymic discharges. These are spontaneously generated bursts of individual motor unit potentials with each burst recurring rhythmically or semirhythmically, usually several times per second. It involves facial muscles more commonly than those of the extremities, and is most often seen in association with Guillain-Barre syndrome, multiple sclerosis, radiation plexopathy, pontine tumors, and timber rattlesnake envenomation. An alteration in the biochemical microenvironment of axon membranes at one of the various sites along the motor axon is the likely basis for the altered membrane excitability that underlies the myokymic discharges in most cases. The similarity of these discharges to those seen with hypocalcemic tetany, and the ability to manipulate myokymic discharges by altering serum-ionized Ca++, suggests that decrease in the ionized Ca++ in the microenvironment of the axon may play an important role. PMID- 1745277 TI - Muscular dystrophy with separate clinical phenotypes in a large family. AB - This report describes a large consanguineous family with muscular dystrophy in 23 patients showing intrafamilial variation of clinical expression. One main variant appeared in the first decade with proximal muscle weakness progressing over the next 20 years to wheelchair confinement, and appeared compatible with classical limb-girdle muscular dystrophy. The other main variant showed onset of distal muscle weakness in lower limbs in the third or fourth decade, progressing very slowly without greater disability throughout the lifetime. Tibial muscle weakness and wasting were clinical landmarks in this variant, but computed tomography of skeletal muscle revealed focal areas of fatty degeneration also in truncal, pelvifemoral, and distal leg muscles in a way not previously reported in distal myopathy. The overall difference in clinical findings between these main variants would suggest 2 separate genetic entities, genealogical data makes a common genetic background possible. PMID- 1745278 TI - Comparison of vibrotactile thresholds with physical examination and electrophysiological assessment. AB - Measurement of cutaneous vibrotactile thresholds may be useful for assessment of the functional integrity of the somatosensory system. To validate a rapid method of determining vibrotactile thresholds that uses a commercially available electromechanical device, vibrotactile thresholds were compared with standardized physical examination findings of sensory function and electrophysiological parameters in 79 patients referred to the Mount Sinai Hospital Neurophysiology Laboratory for clinical electrophysiological evaluation. A statistically significant monotonic association between graded physical examination of vibration perception and vibrotactile threshold was observed for all digits tested in the upper and lower extremities. Statistically significant associations were also observed between vibrotactile thresholds and a variety of electrophysiological measures of the median, ulnar, tibial, peroneal, and sural nerves. The strongest associations were observed between great toe vibrotactile thresholds and late response latencies measured in nerves in the lower extremities. Determination of vibrotactile thresholds may be useful in settings where quantitative measures of large fiber nerve function are desirable and electrophysiological study is not feasible. PMID- 1745279 TI - Muscle histology in Becker muscular dystrophy. AB - Twenty patients with Becker muscular dystrophy (BMD), confirmed by dystrophin tests, were studied histologically. There were several morphological differences between younger (less than or equal to 15-year-old) and older (greater than 15 year-old) patients. In the younger patients, active muscle fiber necrosis followed by a regenerating process was conspicuous. In the older patients, the active degenerative changes appeared less prominent and, instead, more chronic myopathic changes such as moth-eaten fibers, fiber splitting, and hypertrophic fibers were evident. These age-dependent differences in the pathology of BMD were irrespective of the duration of clinical symptoms, i.e., BMD patients of a similar age showed a similar morphological feature regardless of age at onset. Although the presence of mild fiber type grouping and some small angulated atrophic fibers suggested a certain degree of neurogenic involvement, none of biopsies showed significant grouped atrophy as seen in neuropathic disorders. There was no correlation between the histological changes and the specific dystrophin abnormality. PMID- 1745280 TI - Central conduction and autonomic nervous function in HMSN I. AB - CNS conduction and autonomic nervous function were investigated in 15 patients with HMSN I. Central motor conduction time (CMCT) was estimated with magnetic brain stimulation and electrical nerve root stimulation. Somatosensory evoked potential (SEP) and visual evoked potential (VEP) were used for assessment of central sensory and visual conduction. Autonomic effector organ functions were assessed with the R-R variation test for parasympathetic function, and the sympathetic skin response test (SSR) for skin sympathetic sudomotor activity. Five of the patients had prolonged CMCT. Central sensory conduction was normal in 3, and slightly prolonged in 1 of the patients, but could not be estimated in 11 due to lack of response from the cervical recording. VEP was abnormal in 2 patients. R-R variations during normal breathing were low in 8 of 15 patients, and low also during deep breathing in 1 of 15. The SSR test was pathological in 5 of 15 patients. Thus, impaired central conduction and/or autonomic dysfunction was not an uncommon finding in patients with HMSN I. PMID- 1745281 TI - Autonomic function in hereditary motor and sensory neuropathy (Charcot-Marie Tooth disease) AB - Autonomic tests of heart rate and blood pressure control using both invasive and noninvasive techniques were performed on 11 patients with hereditary motor and sensory neuropathy (HMSN) types 1, and 4 patients with HMSN type 2. The results were compared with those of 76 control subjects. No significant difference was found between the patient and control groups. Impairment of sweating on the extremities was found in patients with HMSN types 1 and 2, consistent with distal degeneration of sympathetic fibers in peripheral nerves, but there were no abnormalities of cardiovascular reflex control mechanisms. PMID- 1745282 TI - Effect of statistical methodology on normal limits in nerve conduction studies. AB - Mean +/- 2 standard deviations (SD), which relies on a Gaussian distribution, has traditionally been used to derive normal limits for nerve conduction studies. Our purpose was to examine skew in nerve conduction study (NCS) parameters, and to compare normal limits derived by several alternative methods. We examined 22 NCS parameters from 75 asymptomatic, nondiabetic men (controls). The coefficient of skewness (g1) was significantly positive (P less than 0.10, two-tailed test) in 5 of 8 amplitude and 6 of 8 latency measurements. Transformation reduced g1 in 19 of 22 parameters, and was optimal when g1 was closest to zero. For each measurement, ideal normal limits were defined as mean +/- 2 SD of the optimally transformed data of the control subjects. The percentage of 66 diabetic subjects classified as abnormal by the raw data, but normal by the ideal normal limits, was the positive misclassification rate; while the percentage considered normal by the raw data, but abnormal by the ideal normal limits, was the negative misclassification rate. Mean +/- 2 SD of the raw data produced up to 11% positive misclassifications and 12% negative misclassifications. When the range of observed values was used, up to 6% positive misclassifications and 13% negative misclassifications were found, while the 2.5 or 97.5 percentile values produced up to 10% positive misclassifications and 13% negative misclassifications. We conclude that analyses using the raw data to derive normal limits result in an unacceptable rate of misclassification. Normal limits should be derived from the mean +/- 2 SD of the optimally transformed data. PMID- 1745283 TI - Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy. AB - Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process. PMID- 1745284 TI - Martin-Gruber anastomosis and unusual sensory innervation of the fingers: report of a case. AB - We report the electrophysiological study of a patient with carpal tunnel syndrome who, besides the features of median nerve entrapment at the wrist, showed an aberrant motor innervation of Martin-Gruber type and an unusual distribution of the sensory innervation of the fingers. Studies based on collision between sensory volleys showed that the fibers supplying the anomalous innervation did not follow the same path as the aberrant motor fibers. This finding is consistent with the hypothesis that Martin-Gruber anastomosis is made up of motor axons only, and supports the idea that other abnormalities of innervation may be found in patients with Martin-Gruber anastomosis. PMID- 1745285 TI - Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barre syndrome. AB - In studies of Guillain-Barre syndrome, functional deficit is usually assessed according to a functional scale consisting of several categories. The level of interobserver agreement in this scoring method is not known; furthermore, this method seems to be insensitive when applied to bedridden and artificially ventilated patients. We have developed an additional score (MRC-sumscore), reflecting muscle strength in general. Both scoring methods, tested in Guillain Barre patients, have an almost perfect interobserver agreement. For the functional score kappa = 0.85, and for the MRC-sumscore r2 = 0.96. The MRC sumscore is easily assessed and more sensitive than the functional score when patients are bedridden or artificially ventilated. PMID- 1745286 TI - Maximal and minimal motor nerve conduction velocities in patients with motor neuron diseases: correlation with age of onset and duration of illness. AB - We measured the maximal and minimal motor nerve conduction velocities of the ulnar nerve in 17 patients with spinal muscular atrophy (SMA), 27 patients with amyotrophic lateral sclerosis (ALS), and 40 age-matched control subjects. Crude values of the maximal and minimal motor nerve conduction velocities were reduced in both patient groups, but their difference in each patient was not statistically different from that of a control subject. The conduction velocities adjusted according to each patient's age were faster in SMA patients than in ALS patients. Among patients with either ALS or SMA, the age-adjusted conduction velocities were larger in those who had developed the disease at younger ages and suffered from it for shorter periods of time. These findings suggest that the motor nerve fibers regenerate more in younger patients in the early stages of the disease, particularly in SMA. PMID- 1745287 TI - Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model. AB - Changes in nerve fiber numbers distal to a nerve repair in the sciatic nerve of 48 rats were evaluated over a 1- to 24-month period. The results of the morphometric evaluation in the sciatic nerve distal to the nerve repair demonstrated an increase in nerve fiber counts as early as 1 month following the nerve repair. The number of nerve fibers in the distal nerve was greatest at 3 months and did not return to normal levels until 24 months. The results of this study will influence the timing of experimental studies in which nerve fiber counts are critical for evaluation, and provides a better understanding of the clinical events occurring following nerve repair. PMID- 1745288 TI - The numbers and relative sizes of motor units estimated by computer. AB - A fully automated system is described for estimating the numbers and relative sizes of functioning motor units in proximal and distal muscles of the arm and leg. In this system, a computer controls the motor nerve stimulation, and analyzes the potentials evoked from the muscles; a subprogram searches for instances of "alternation." In 33 healthy volunteers, aged 21 to 56 years, the median-innervated thenar muscles of one hand were tested 2 to 3 times; the mean motor unit estimate was 228 +/- 93 SD. For similar numbers of biceps brachii, extensor digitorum brevis, and vastus medialis muscles, the respective mean values were 113 +/- 40, 131 +/- 45, and 229 +/- 108 units. The reproducibility of the method was such that the overall coefficient of variation, for the normalized results from the 121 muscles studied, was 22%. The reliability of the automated method was doubled if 3 estimates, rather than one, were performed on each muscle. Comparisons of the results obtained by automated and "manual" methods indicated that the computer-derived values tended to be lower by approximately 33%. PMID- 1745289 TI - Uni- and bipolar surface recordings of human nerve responses. PMID- 1745290 TI - Schwartz-Jampel syndrome with dominant inheritance. PMID- 1745291 TI - Ryan White HIV C.A.R.E. program. PMID- 1745292 TI - "The brown bag" and other approaches to decreasing polypharmacy in the elderly. PMID- 1745293 TI - Understanding Medicare. PMID- 1745294 TI - I live by the color of thin plastic strips. Managing a case of hard-to-control diabetes. PMID- 1745295 TI - Wrinkles. PMID- 1745296 TI - The difficulty of deciding why children die. A review and some recommendations. PMID- 1745297 TI - Achilles and his evil squeeze. Colchicine poisoning. PMID- 1745298 TI - Affirming physicians' professionalism against the destructive influence of private third party relations. Durham-Orange County resolutions. PMID- 1745299 TI - Comment on cocaine-induced mesenteric ischemia article. PMID- 1745300 TI - Comment on DWI (driving while impaired) article. PMID- 1745301 TI - [Dental ethics, esthetics and cosmetics]. AB - By means of adhesive dentistry sound teeth can be made more beautiful without damaging tooth structure. This is called cosmetic dentistry. Within the dental profession there is a discussion about the following questions: is cosmetic dentistry real dentistry? Is it ethical to render cosmetic services to patients? In this article arguments are displayed to answer this question in a positive manner. PMID- 1745302 TI - [Cosmetic aspects of dental treatment]. AB - Communication between the dentist and his patient is an absolute condition for successful cosmetic dentistry. The patient must have possibilities to explain his wishes and expectations to the dentist (and if an indirect technique is used, to the dental laboratory). In this article methods are described and hints are given to arrange this in dental practice. PMID- 1745303 TI - [Shape and/or colour anomalies of anterior teeth]. AB - Many esthetically unpleasant positions of teeth can be improved by orthodontic treatment but can also be camouflaged by built-ups with composite resins in combination with grinding of enamel. With this method orthodontic results can also be improved and relapses corrected. The technique and different possibilities are described and demonstrated with clinical examples. PMID- 1745304 TI - [Guidelines for treatment of missing anterior teeth]. AB - The orthodontic treatment of patients with missing incisors should be directed to avoid prosthetic solutions. Specific rules have to be applied for the closure of spaces due to missing teeth to reduce the occurrence of papillae retraction and to place the substituting teeth in such a position that their crowns can be built up to look like the ones they replace. To realize these goals the mesiodistal angulations should deviate from the standard ones, a proper distribution of crown width should be achieved and finally a permanent retention with a palatally bonded thin multi-stranded wire should be installed in most cases. PMID- 1745305 TI - [Periodontology and esthetics: the gingival recession]. AB - Gingival recessions are regarded by many people as an esthetical problem. Successively the etiology, the significance and the indications for therapy are discussed. Different kinds of therapy such as oral hygiene instruction, the free gingival graft and various pedicle grafts are explained. Finally it is advocated that surgical kinds of therapy have to be applied with reservedness. PMID- 1745306 TI - [Bleaching of teeth: a review]. AB - Bleaching of vital and non-vital teeth is becoming a routine procedure in esthetic dentistry. In a relative safe way many types of discoloration can be treated. Four treatment systems are available at present. For an appropriate choice it is essential to know the cause of the discoloration. Long term results are still scarce. Most treatment systems show slight to moderate side-effects, varying from demineralisation of enamel to soft tissue problems. PMID- 1745307 TI - [Cosmetic dentistry and adhesive prosthodontics]. AB - A better chemical bonding to metals offers the opportunity to bind composites onto metal and metals onto tooth structures. This may lead to an increase of adhesive prosthetic and cosmetic treatments. In this article some applications of this modern treatment method are described, anterior and posterior, in solitary elements as well as multiple bridge constructions. PMID- 1745308 TI - [Esthetic aspects of crowns and bridges]. AB - By means of discussing several guiding principles a protocol is suggested and treatment procedures are outlined which will result in optimum esthetics in the fabrication of crowns and bridges. Some important considerations in restoring an occlusion with porcelain are discussed. PMID- 1745309 TI - [Etched porcelain]. AB - Porcelain is an outstanding material for tooth restoration with splendid cosmetic results. With the introduction of porcelain it is possible to restore teeth with minimal loss of healthy tissue. This results in strong and beautiful restorations. PMID- 1745310 TI - [Longevity of restorations in composite and etched porcelain]. AB - Due to continuing alterations in composition of dental products and materials, prognoses about longevity of restorations in composite or etched porcelain are extremely difficult to make. Strength, wear resistance and resistance against disintegration determine durability of stress bearing restorations. Elasticity in combination with bond strength are determinant for prevention against premature leakage. Indication, cavity form and careful handling of the materials are prerequisites for longevity of the restoration. The prognosis of the favourably located but stress bearing class IV is far better than that of the unfavourable located, non stress bearing class V-composite restoration. For the etched porcelains, the veneers offer the best perspectives with respect to durability thanks to the favourable shrinkage pattern. PMID- 1745311 TI - [Results of hemisections and root amputations in a general practice]. AB - A retrospective study is presented of the treatment of furcation problems and deep, localized periodontal pockets by means of root-resection and the subsequent restorative treatment. The study incorporates 69 teeth in 53 patients, treated in the period 1970-1986. The results indicate that well-indicated root-resections may produce good long-term results. Most of the treated teeth have a survival rate of 10 years. Indications, possibilities and specific restorative problems are discussed. PMID- 1745312 TI - [Pain and painkillers. 3. Psychic component]. AB - Psychic factors, for instance anxiety and the social and cultural environment, affect the tolerance for pain, amongst others due to an influence on the 'gate control' mechanism. Therefore psychopharmaca, which affect the brain, but also a placebo may be used to fight pain. Through three types to distinguish in learning, chronic pain may result in illness-behaviour. PMID- 1745313 TI - [The dental profession in The Netherlands before 1865]. AB - The dental profession before 1865 has been described with the help of sources from the 19th century, in combination with prosopographical research. During this period, dentists had no exclusive rights in dentistry: other surgical professions were also involved both with its theory and practice. Their specialised colleagues comprised a group of 137 dentists, largely related to a few Jewish families. This characteristic, underlined by their intensive migration and training within the family, had been responsible for the divergent position of the dentists in Dutch medical legislature of the 19th century. While in the medical profession the organisation and structure (1865) was the first te be revised, followed by a reorganisation of education (1876); in dentistry the recruitment and education had to be reformed (1865-1876) before the building up of a new professional structure. This process speeded up by the rapid mortification of the ancient group of dentists. PMID- 1745314 TI - [The history of pain control in dentistry in The Netherlands]. AB - Pain control in The Netherlands used to be in the hands of surgeons. Dentists were not allowed to use any drugs which could have a general effect. In the Anglo Saxon countries dentists and anaesthesiologists working together since 1846 have achieved a high standard of pain control. Anaesthesiology has been recognised in The Netherlands only since 1948. The advantages of a sequence of possibilities for pain control have since become available for dentistry in The Netherlands. PMID- 1745315 TI - [Esser (1877-1946) and the dawn of maxillofacial prosthetics in The Netherlands]. AB - A short historical review is presented of the development from simple facial plates towards complex maxillofacial prostheses. There was an impetuous demand for extended development of this type of prostheses during World War I. The Dutch plastic surgeon Esser developed the skin-graft-inlay technique facilitating in a relative easy way extensive maxillofacial reconstructions. The technique was published in English and German and was soon used by surgeons on both sides. The combined training of Esser in medicine and dentistry was advantageous for the development of the technique. PMID- 1745316 TI - [The founding and the first years of the first Dutch Dental Association: Nederlandsch Tandheelkundig Genootschap]. AB - During the last half of the 19th century dentistry in the Netherlands met little social appreciation. The charismatic leader of Dutch dentistry, Dr. Theodore Dentz, dentist and physician, took the initiative to found the first Dutch dental organisation in 1880. His goals were to improve the image of his profession, to strive for better education and to strengthen the bond between the best dentists in the country. After about 1910 changes in society and dentistry forced 'het Genootschap' to delegate their work in the field of social and professional representation to the newly founded Dutch Dental Association. After that time 'het Genootschap' converted itself into a scientific invitation society. PMID- 1745317 TI - Clinical significance of computed tomography in early aneurysm surgery. AB - The significance of computer tomographic findings for the analysis of complications or the course and prognosis after early aneurysm surgery was analyzed on the basis of 100 patients consecutively operated on for ruptured cerebral aneurysms. Intracerebral or extended intraventricular hematomas were a poor prognostic sign. An acute hydrocephalus had a negative effect only on the early course but not on the final results. Nearly all (94) of the patients presented postoperatively with a cerebral volume increase either by CSF release, edema, and/or vasoparalysis. A correlation with the final result could not be observed. Twenty-two patients presented with ischemic infarction in the postoperative CT scan, one had hemorrhagic infarction. In 19 of the 22 cases the cause of the infarction could be related to the surgical trauma. In 10 cases it remained asymptomatic. In only one case vasospasm was responsible for a symptomatic infarction. The findings show that early surgical repair of a ruptured cerebral aneurysm is an effective method to prevent rebleeding and ischemic infarction by vasospasm. The hemorrhage and the operation, however, are followed by a large number of visible morphological lesions in the CT scan. PMID- 1745318 TI - The effect of tranexamic acid on bleeding time and haemostasis. AB - The effect of tranexamic acid (TXA) on platelet function was examined in 37 patients with ruptured intracranial aneurysms. TXA was administered in a double blind, placebo controlled manner to 37 patients with ruptured intracranial aneurysms. TXA was given to 17 patients in a dose of 9 g/24 hours, to another 6 patients in a dose of 6 g/24 hours; 14 patients were given a placebo. The effect of TXA on certain haemostatic function tests was evaluated between the treatment groups. We conclude that patients receiving TXA do not appear to be at risk of recurrent haemorrhage due to abnormal haemostasis. PMID- 1745319 TI - The role of sinus thrombosis in occipital dural arteriovenous malformations- development and spontaneous closure. AB - Two cases of dural arteriovenous malformations are presented. Both were associated with thrombosis of the sigmoid sinus. Without any treatment, recanalization of the sinus occurred in one case, while the dural arteriovenous malformation was persisting. In the second case, recanalization of the sinus coincided with the spontaneous closure of the malformation. The interrelationship of sinus thrombosis and dural arteriovenous malformations, and the possible mechanism of spontaneous closure are discussed. PMID- 1745320 TI - Clinical pattern of chronic subdural haematoma. AB - To assess the clinical manifestation of chronic subdural haematoma (CSH) the authors retrospectively analysed the files of 131 adult patients treated in the Department of Neurosurgery Medical Academy of Lodz. In 14 patients the illness had a sudden onset, suggesting cerebral stroke. 50% of patients had symptoms of raised ICP, there were no differences between young and older patients. In patients older than 40 years focal neurological deficits were more frequent, and in 13% of them focal signs were homolateral to CSH. In 9 patients the lesion produced symptoms of transtentorial herniation within a very short period. The authors think that despite the great progress in neuroradiology and neurosurgery, the condition may still be overlooked if the clinical picture does not suggest an intracranial space-occupying growth. PMID- 1745321 TI - Spinal subarachnoid hematoma of unknown etiology. A case report. AB - A case of spinal subarachnoid hematoma at T3-T7 level is reported in a 60-year old hunter, who developed progressive spinal cord impairment after receiving the recoil of his shotgun. Both clinical and neuroradiological investigations, including the selective spinal angiography, failed to demonstrate the origin of the bleeding. The combination of an apparently trivial spinal trauma with temporary increase of the intrathoracic pressure might be considered as possible etiologic factor. PMID- 1745322 TI - Balloon occlusion of carotid-cavernous fistula via subtemporal transdural approach. AB - This is a report on a patient with traumatic carotid-cavernous sinus fistula (CCF). She gradually noticed noise in her head and suffered from partial ophthalmoplegia. Angiography demonstrated a left high flow CCF. She underwent a direct surgical treatment with a detachable balloon because an endovascular balloon embolisation for the CCF had been unsuccessful. Immediate disappearance of the bruits after surgery was noted and the patient recovered progressively her ophthalmoplegia. Follow angiograms 3 months after surgery revealed the disappearance of the fistula and an appearance of a false aneurysm. She is asymptomatic and periodically monitored in the outpatient clinic. PMID- 1745323 TI - Nimodipine evoked dilation of cerebral arteries early during the development of late vasospasm in subarachnoid hemorrhage. AB - In subarachnoid hemorrhage (SAH) late cerebral ischemia may develop without significant visible narrowing of arteries at angiography, but in severe ischemic conditions "vasospasm" invariably seems to be present. The majority of patients with aneurysm rupture develop some degree of vasospasm, whereas relatively few suffer from ultimate brain infarction. The prophylactic use of the calcium antagonist Nimodipine is linked to a beneficial anti-ischemic effect in SAH, although narrowing of large bore arteries still seems to develop despite administration of this drug. Attenuation of vascular spasm, mainly in the arterioles has been implicated as the major mechanism of action, although a neuronprotective effect of Nimodipine has been suggested as well. The present paper presents fragmentary evidence that Nimodipine does elicit a vasoactive response in the cerebral vasculature early during the development of late cerebral vasospasm, and that this response seems closely linked to reversal of attendant ischemic symptoms. PMID- 1745324 TI - [Abscess of the pyramidal apex]. AB - The authors report on one case of an abscess at the pyramidal apex. The 52-year old male patient presented with pareses of the fifth and seventh cranial nerves and hypacusis on the right side. After diagnostic procedures (CT-scan, carotid angiography), a tumor at the apex of the right pyramid was expected. During surgery a large encapsulated mass was found containing pus. A bacterial agent could not be isolated. The abscess bordered on the mucosal lining of the sphenoid sinus and on the cells of mastoid bone. The starting point of an abscess at the pyramidal apex is most commonly an otitis media, most frequently caused by staphylococcus. Sterile abscesses are seen in almost 20%. Of differential diagnosis on has to keep in mind other space-occupying lesions especially epidermoid or dermoid cysts. PMID- 1745325 TI - Ganglioside therapy and Guillain-Barre syndrome. A historical cohort study in Ferrara, Italy, fails to demonstrate an association. AB - We investigated an alleged association between ganglioside therapy and the risk of developing the Guillain-Barre syndrome (GBS) in a historical cohort study. Using official medical records of the Local Health Unit No. 31 of Ferrara Province, northern Italy, we linked data on sales of gangliosides with information regarding hospital admissions and discharge diagnoses between January 1, 1988, and May 31, 1990. The number of incidence cases of GBS observed within 30 days of gangliosides administration in a cohort of 13,373 treated subjects (0.0 cases) was not significantly different from that expected in the general population (0.014). Our study suggests that patients receiving gangliosides are not at increased risk of developing GBS. However, because of sample size limitations, these findings should be confirmed in a larger cohort study. PMID- 1745326 TI - Amyotrophic lateral sclerosis in southern Greece: an epidemiologic study. AB - All amyotrophic lateral sclerosis cases hospitalized over a 25-year period in the University Department of Neurology in Athens were surveyed, with emphasis given to the occupation of the patients and the geographic distribution of the disease. The results showed an overrepresentation of farmers among patients and an aggregation of cases in the region of Cephalonia. These findings might suggest that environmental factors could be involved in the etiology of the disease. PMID- 1745327 TI - Risk factors in motor neuron disease: a case-control study. AB - A case-control study of risk factors in 512 cases of motor neuron disease (MND) and 512 controls, affected by other neurological diseases, was performed. Clinical history showed a significant increase in gastric ulcer and mechanical injuries among MND cases, whereas the frequencies of operations, poliomyelitis, malignancies and autoimmune diseases were similar for cases and controls. The women affected by MND had a later menarche and an earlier menopause; therefore, the reproductive period was significantly shorter, supporting a possible role of sexual hormones in the pathogenesis of MND. The analysis of occupations showed an increased number of farmers and also of subjects exposed to chemical products among MND cases. PMID- 1745328 TI - Epidemiology of progressive muscular dystrophy in Okinawa, Japan. Classification with molecular biological techniques. AB - We studied the prevalence of various types of progressive muscular dystrophy (PMD) in Okinawa, Japan on December 31, 1989 and the incidence of Duchenne muscular dystrophy (DMD) in 5-year periods from 1957 to 1985. We classified patients with PMD clinically, electrophysiologically, molecular biologically and immunohistochemically with antidystrophin antibody, especially for sporadic cases of DMD, Becker muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LG). The prevalence for all PMD in Okinawa was 7.13 X 10(-5) for DMD, 1.82 X 10(-5) for BMD in the male population, 1.55 X 10(-5) for LG, 1.14 X 10(-5) for congenital muscular dystrophy, 2.03 X 10(-5) for facioscapulohumeral muscular dystrophy (FSH), and 9.13 X 10(-5) for myotonic dystrophy (MD) in the total population. The incidence of DMD in the period 1957-1985 was 15.41 X 10(-5) live born males (LBM) and 3.21 X 10(-5) LBM for BMD. The incidence has apparently declined in Okinawa since 1975. The prevalence of BMD, FSH and MD was rather high in Okinawa compared with previous reports. Molecular biological techniques for classifying patients were indispensable for the epidemiological study of PMD. PMID- 1745329 TI - Multiple sclerosis in Galion, Ohio: prevalence and results of a case-control study. AB - An investigation of the occurrence of multiple sclerosis (MS) was undertaken in the City of Galion, Ohio, USA, because of a report of an increased number of cases. As of June 1, 1987, there were 18 living cases of MS in Galion and Polk Township, for a prevalence rate of 112 cases per 100,000 population. The expected rate is approximately 65-170 cases per 100,000. In a case-control study, residents of Galion or Polk Township who had MS were compared to residents who did not have MS. The controls were matched to the cases on age and sex and had lived in Galion for at least as long as their matched case. The cases and controls did not differ in the distribution of their present or past Galion addresses, occupational histories or workplace exposures. Cases were more likely to have graduated from high school and college than controls. Cases were more likely than controls to report a history of allergies, to recall two or more relatives who had neurologic diseases that began before their first MS symptoms, to report owning a cat that died of unexplained causes and to recall having received oral polio vaccine. Cases and controls had similar levels of antibodies to measles, chickenpox, cytomegalovirus and the human T-cell lymphotrophic virus I. PMID- 1745330 TI - Epidemiology of lissencephaly type I. AB - In a cooperative study in The Netherlands 22 patients with lissencephaly type I were collected. In the period 1980-1988, the prevalence of lissencephaly type I in the Netherlands was 11.7 per million births (12.2 for females and 11.0 for males). The 5-year survival rate of patients with a complete or nearly complete agyria (grade 1 or 2) in this study was 54% compared to 91% in patients with a mixture of agyria with pachygyria or complete pachygyria (grade 3 or 4). PMID- 1745331 TI - Regional disparities in the annual prevalence rates of Parkinson's disease in Canada. AB - Parkinson's disease (PD) rates were examined by province and by sex for Canada for the years 1979-1984. As seen with other studies, PD displayed an uneven geographic distribution in the average annual prevalence rates for both males and females. The distribution of prevalence rates indicated a higher prevalence of PD in the western-most provinces. Nationally, males had a statistically significantly higher prevalence than females. Three provinces displayed a statistically significant sex difference with 2 provinces having a higher prevalence rate among males and 1 with a higher prevalence among females. The uneven distribution of prevalence rates offers some support for the involvement of environmental influences in the etiology of PD. PMID- 1745332 TI - Smoking and stroke. AB - The purpose of this review is to evaluate literature published since 1978 on the association between smoking and stroke. Two cohort studies found a dose-response relationship between the amount of cigarettes smoked per day and the relative risk of stroke. Also, two of the cohort studies found that when smoking ceased, the risk of stroke lessened (p less than 0.001). Nine case-control studies found a significant association between smoking and stroke for men and women. The biological association between smoking and stroke is plausible and several epidemiologic studies are supportive of this thesis. Additional, well-designed epidemiologic studies with a sufficient sample size to detect reasonably small odds ratios or relative risks (thus providing adequate statistical power) are warranted. PMID- 1745333 TI - Reflections on the difficult task of the Academic Medical Center. PMID- 1745334 TI - [Structure and function of receptors for C3 cleavage fragments]. AB - Most of the biological effects derived from complement activation depends on interactions between cleavage fragments of complement components and cells bearing specific receptors. This review overviews structure and function of receptors for C3 cleavage fragments. Genes encoding for CR1, CR2 and CR3 have been cloned and they code for integral transmembrane glycoproteins which function as cellular receptors for human C3b, C3dg/C3d and C3bi fragments respectively. These receptors have a wide cellular distribution and participate in transport of immune complexes, phagocytosis and regulation of immune response. Alterations of expression of these molecules are observed in pathology. PMID- 1745335 TI - [Double profile dialysis: ultrafiltration and sodium variable description and clinical validation in the child]. AB - Despite significant technical improvements (bicarbonate dialysate, volumetric ultrafiltration control) high intradialytic ultrafiltration is troublesome in children, specially in the proportion of patients presenting a normal or low blood pressure even with overweight. We used, in this group of children (overhydratated without vascular repercution) a modelling of both sodium and ultrafiltration during dialysis, in order to achieve dry body weight without increasing session time despite hypotension risks. The usefulness and practicability of sodium and ultrafiltration modelling together during dialysis in children is analysed in a short time study (for plasma volume changes calculation) and in a long term follow up study over a year (for clinical tolerance). Today, we reserve this form of dialysis only for a single session needed by overhydratation (more than 5% of dry body weight) in order to achieve dry body weight maintaining dialysis session time constant without increasing side effects (hypotension). PMID- 1745336 TI - [Extramembranous glomerulonephritis induced by lithium]. AB - We report the case of a patient who developed a nephrotic syndrome after lithium carbonate therapy. The nephrotic syndrome disappeared after withdrawal of therapy and recurred when the patient was rechallenged with the same drug. This seems a convincing argument to believe that lithium was the causal agent. Renal biopsy specimens showed membranous nephropathy, suggesting that immune-complex formation was involved in the reaction to the drug. Membranous nephropathy is an exceptional and benign hazard during lithium therapy, and underlines the need for periodic urinalysis in patients treated with the drug. PMID- 1745337 TI - [Comparison of calcium acetate and calcium carbonate for the control of predialysis hyperphosphatemia]. AB - The present study was conducted to determine whether half the dose of elemental calcium given as acetate (Ca Ac) could control on medium term the predialysis plasma phosphate as well as calcium carbonate (CaCO3) while inducing less frequent hypercalcemia. This was evaluated in a cross-over study of 3 periods of 10 weeks according to the sequence Ca Ac, CaCO3, Ca Ac, in 12 compliant patients on chronic dialysis previously treated by Ca CO3. Because of poor tolerance of Ca Ac during the first period 4 patients were excluded and the results have been assessed only on the 8 patients who completed the study. For half the doses of elemental calcium (620 +/- 250 mg versus 1310 +/- 560 mg versus 710 +/- 200 mg/day) Ca acetate allowed the same control of predialytic hyperphosphatemia (1.67 +/- .34; 1.74 +/- .32; 1.75 +/- .38) with paradoxically comparable normal mean plasma calcium concentration (2.61 +/- .14; 2.56 +/- .13; 2.55 +/- .14 mmol/l). Plasma alkaline phosphatases and intact PTH concentrations remained also stable during the 3 periods. The frequency of hypercalcemia greater than 2.75 mmol/l (12; 9; 20%) and of hyperphosphatemia greater than 2 mmol/l (17; 22; 27%) were comparable with the 2 treatments. We conclude that calcium acetate controls predialytic hyperphosphatemia as efficiently as CaCO3 for half the dose of elemental calcium without however decreasing the frequency of hypercalcemia. PMID- 1745338 TI - Neurologists--1990. AB - The American Medical Association Physician Masterfile for 1990 contains 13,705 physicians who consider neurology their primary, secondary, or tertiary specialty. Of these, 7,036 are board certified and 10,065 designated neurology as their primary specialty. Although there has been a steady increase in the number of women, the vast majority of neurologists are men and less than 50 years old. Two-thirds provide direct patient care as their major activity and 15% are in training. There are almost as many neurologists employed by hospitals, medical schools, and government entities (40%) as there are working alone or in group practice (48%). The actual number of neurologists is compared with earlier projections of neurology needs for 1990. Since forecasts, in the absence of more detailed information, can become the reality of public policy decisions, neurologists will need to become increasingly informed about the many unique benefits they provide to their patients. PMID- 1745339 TI - The biologic basis for the treatment of acute stroke. AB - This is a review of therapeutic modalities that have been utilized in the treatment of stroke. Each is based upon data obtained from the study of the biologic events that occur during experimentally induced cerebral ischemia in animals. The type of information obtained from these studies could not have been obtained in any other manner. Despite the apparent effectiveness of some of these modalities in modifying stroke in animals, their application to humans with stroke has been disappointingly ineffectual. The delay between onset of stroke symptoms and initiation of treatment is usually several hours or more, which may be too late to rescue ischemic neurons. In order to be effective, treatment will have to be initiated as early as possible (preferably within 1 hour) to take advantage of the biologic window of opportunity. There is evidence that this can be accomplished by proper planning and training of personnel. PMID- 1745340 TI - Long-term benefit from prednisone therapy in Duchenne muscular dystrophy. AB - Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years. PMID- 1745341 TI - Hearing loss in facioscapulohumeral muscular dystrophy. AB - The coincidence of facioscapulohumeral muscular dystrophy (FSHD) with sensorineural hearing loss and retinal abnormalities might imply genetic heterogeneity of FSHD. We performed screening audiometry in 56 patients with autosomal dominant FSHD and in 72 healthy family members, and found that the difference in hearing level between 4,000 Hz and 6,000 Hz was significantly greater in FSHD patients than in controls, independently both for the left and right ear. We conclude that this change of hearing function is part of the disease and may lead to severe hearing loss in some patients. The fact that it was present in all families is another argument against genetic heterogeneity. PMID- 1745342 TI - Clinical discriminators of lobar and deep hemorrhages: the Stroke Data Bank. AB - Of the 1,805 patients with acute stroke enrolled in the Stroke Data Bank, 237 had parenchymatous hemorrhage. After excluding 34 secondary intracerebral and 31 infratentorial hemorrhage patients, a logistic regression analysis of the 172 patients with primary supratentorial intracerebral hemorrhage (ICH) elucidated clinical factors that distinguished the 65 patients with lobar hemorrhage (LH) from the 107 patients with deep hemorrhage (DH) located in the basal ganglia and thalamus. In LH, severe headache was more common than in DH, while hypertension and motor deficit were significantly less common. Patients with either LH or DH had a similar prognosis and mean Glasgow Coma Scale (GCS) scores, despite the hematoma volume measured on the initial CT being significantly greater for LH than DH. The presence of intraventricular extension (IVH) was more frequent in DH. The frequency of IVH increased with hematoma volume in LH, but remained constant for DH. Two CT variables (IVH and hematoma volume) that differed in these two hemorrhage groups were important predictors of coma (GCS less than or equal to 8) in a logistic regression model. Differences in the frequency of IVH may help explain why the degree of impairment in consciousness was similar in the two groups. Among patients with supratentorial ICH, location of the hematoma is related to both volume and IVH, which are important determinants of the level of consciousness. PMID- 1745343 TI - Prevalence of Alzheimer's disease and other dementias in an elderly urban population: relationship with age, sex, and education. AB - We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimer's disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education. PMID- 1745344 TI - Accelerated intracranial occlusive disease, oral contraceptives, and cigarette use. AB - We report clinical and angiographic features of accelerated intracranial occlusive disease resembling moyamoya vasculopathy in five young women who used oral contraceptives (OCs) and smoked cigarettes, but generally had no other obvious risk factors for cerebrovascular disease. Three women had been on OCs for at least 4 years, one woman each had been on OCs for 3 months and for 2 weeks. All five women had smoked cigarettes for at least eight pack-years. Intermittent and progressive multifocal cognitive, visual, motor, or sensory hemispheric symptoms and signs developed in all. All patients developed strokes, four preceded by transient ischemic attacks. Cerebral angiography demonstrated bilateral supraclinoid internal carotid artery stenosis in four patients and proximal posterior cerebral artery stenosis in one. Additional features included rete mirabile, telangiectasias, prominent lenticulostriate collaterals, and multifocal distal cerebral branch occlusions. Three had mild abnormalities of serum fibrinogen, antinuclear antibody, erythrocyte sedimentation rate, or CSF IgG. After discontinuing OCs and reducing cigarette use, four women have not had further strokes over a mean follow-up of approximately 5 years. In certain young women, clinical and angiographic features resembling moyamoya may develop with the use of OCs and cigarettes. We speculate that an immunologically mediated vasculopathy may explain, in part, this unusual cerebrovascular syndrome in otherwise healthy young women. PMID- 1745345 TI - Transcranial Doppler ultrasound identifies patients with right-to-left cardiac or pulmonary shunts. AB - We performed transcranial Doppler ultrasound (TCD) and transesophageal contrast echocardiography simultaneously in four patients. In one patient with a patent foramen ovale and another patient with pulmonary A-V fistulae, we detected micro air bubbles in the right middle cerebral artery three to five cardiac cycles after their appearance in the left atrium following intravenous injection of contrast. In two patients without right-to-left shunts, we did not detect air bubbles in the left atrium or middle cerebral artery following injection of contrast. These results show that TCD can identify patients with right-to-left cardiac or pulmonary shunts. PMID- 1745346 TI - HIV-1 infection and nervous system abnormalities among a cohort of intravenous drug users. AB - A group of 109 HIV seropositive and 51 seronegative intravenous drug users was evaluated for the presence of HIV-1-related neurologic disease using clinical, neurologic, neuropsychological, and electrophysiologic evaluations. About 80% of HIV seropositive subjects had less than two constitutional symptoms. CD4 cell counts were less than 500/mm3 among 56% of seropositive participants; three individuals were receiving zidovudine. Neurologic abnormalities were found frequently among the cohort, independently of HIV-1 serostatus; electrophysiologic abnormalities were uncommon. Participants from both serologic groups scored significantly lower on neuropsychological tests as compared with norms established for a cohort of homosexual men, and there was no clear association between HIV-1 serostatus and performance on these tests. This study suggests that HIV infection was not the dominant cause of neurologic abnormalities among the study cohort. PMID- 1745347 TI - Is the prevalence of dementia changing? AB - We compared the point prevalence rates of dementing illnesses in the population of Rochester, Minnesota, on January 1, 1980, with the previously published rates of January 1, 1975, by using extensive health care records available from all sources of care in the community, in order to identify and classify cases with standard diagnostic criteria derived from DSM-III. The overall age- and sex adjusted prevalence rate per 100,000 population for dementia on January 1, 1980, was 402.5 compared with 388.4 on January 1, 1975; for Alzheimer's disease it was 259.8 in 1980 and 259.5 in 1975. The stability of the rates suggests no change in the incidence and mortality associated with these conditions. The prevalence rates for Rochester, Minnesota, are similar to many other rates estimated in other North American communities, but they differ from two other population-based estimates from East Boston and California. Case definitions and methods of assessment probably account for the differences in estimated prevalence. PMID- 1745348 TI - Visual loss in tuberous sclerosis. AB - Of 11 patients with tuberous sclerosis complex (TSC) treated from 1980 to 1990 for obstructive hydrocephalus secondary to subependymal giant-cell astrocytoma, four had adequate documentation to determine visual outcome. Despite surgical relief of elevated intracranial pressure in all cases, two patients sustained further visual loss. In one patient, visual loss was arrested, and in one patient, it was prevented. Although hydrocephalus is uncommon in TSC, its effects on the optic nerves are serious and eventually irreversible. Because TSC patients may not be able to express early symptoms of increased intracranial pressure, periodic ophthalmologic examination and brain imaging may be advisable when a subependymal lesion has been identified. PMID- 1745349 TI - Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials. AB - We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing. PMID- 1745350 TI - Familial spinal neurofibromatosis: clinical and DNA linkage analysis. AB - We studied two families with an unusual variant of neurofibromatosis (NF). The first family had spinal neurofibromas and cafe au lait spots (CLS), the second spinal neurofibromas without CLS. Other signs of NF1 or NF2, such as cutaneous tumors, Lisch nodules, or acoustic tumors, were absent. The inheritance pattern in both pedigrees was consistent with autosomal dominant inheritance. Using genetic linkage analysis with DNA markers tightly linked to the NF1 and NF2 loci, we determined that the likely location for the mutation in the first family was in the NF1 gene with odds of 97:1, whereas the mutation in the second family was excluded from the NF1 locus with odds greater than 100,000:1. Families such as these, in which a defined subset of the NF phenotype is passed on, are important for understanding the functional consequences of particular mutations in the NF genes. PMID- 1745351 TI - Plasmapheresis in children with Guillain-Barre syndrome. AB - Between 1987 and 1989, we plasmapheresed six children with Guillain-Barre syndrome (GBS). None of the children could walk independently at the start of the treatment, and one was being ventilated. Five patients showed clinical improvement during pheresis, and no significant side effects occurred. The median time from onset of weakness to independent walking for these six children was 17 days. This compares with 43 days for 18 children with GBS in this institution who were given supportive measures only. PMID- 1745352 TI - Differential action of amitriptyline on neurons in the trigeminal nucleus. AB - We studied the effect of amitriptyline (AMI) on neurons in the spinal trigeminal nucleus caudalis in cats anesthetized with alpha-chloralose. The IV injection of 1.0 to 4.0 mg/kg AMI had a differential effect on the inhibitory mechanisms controlling the responses of these neurons. AMI significantly enhanced the segmental inhibition (SI) of wide dynamic range (WDR) neurons but had little or no effect on low-threshold mechanoceptive neurons. AMI also facilitated the SI of some nociceptive specific (NS) neurons and the periventricular inhibition of some WDR and NS neurons, but these effects were not statistically significant. Our observations suggest that AMI exerts its antineuralgic effect by enhancing the ability of SI to prevent excessive firing of WDR neurons. This supports the notion that neuropathic pain is caused by dysfunction of inhibitory mechanisms in the CNS. PMID- 1745353 TI - Systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis. II. Immunologic evaluation. AB - Immunologic functions are studied in conjunction with a placebo-controlled trial of lymphoblastoid interferon (IFN) in patients with chronic progressive (CP) multiple sclerosis. Prior to treatment, CD4+ cells are significantly increased and CD8+ cells decreased in the blood of MS patients. Both CD5+ and CD4+ cells increase significantly with IFN therapy early during the treatment phase of the trial, while the number of CD8+ cells decreases steadily, becoming significant at 6 months. CNS IgG synthesis rates increase with IFN treatment and maximize at 3 months. Serum antiviral activity also increases with IFN treatment. In the IFN treated group, a trend toward improvement, determined clinically and by MRI, likely reflects the influence of a subpopulation of 10 patients. This subpopulation is now further characterized by an early increase in CNS IgG synthesis and numbers of CD5+ cells in the blood. Although these immune functions may identify a number of CP MS patients who might benefit from IFN, it is unlikely that these mechanisms actually mediate the potentially beneficial effects of this cytokine. PMID- 1745354 TI - Self-sustaining limbic status epilepticus. I. Acute and chronic cerebral metabolic studies: limbic hypermetabolism and neocortical hypometabolism. AB - Regional cerebral glucose utilization (RCGU) increases during seizures whereas hypometabolism occurs in postictal and interictal states. Recently, we developed a model of nonconvulsive, self-sustaining limbic status epilepticus (SSLSE) in which electrographic seizures persist 12 to 24 hours after 90 minutes of continuous hippocampal stimulation. The present studies define the functional anatomy of SSLSE and the states thereafter. RCGU was studied by 2-deoxyglucose autoradiography in (1) a group of rats acutely (1 hour after induction) during SSLSE, and (2) two groups of rats chronically (1 week or 1 month) after SSLSE. RCGU measurements in these groups were compared with those obtained in naive and electrode-implanted control rats. In the acute group, there were bilateral increases in RCGU in the hippocampus, retrohippocampal structures, and associated limbic and subcortical nonlimbic regions; hypometabolism was found in several neocortical structures. Chronically, RCGU was elevated in certain limbic areas at 7 days but returned to control values at 30 days. On the basis of our findings, we postulate a feedback network involving the hippocampus and neighboring parahippocampal structures (the hippocampal-parahippocampal "loop") as a critical substrate for establishing limbic system status epilepticus. In addition, the results indicate that metabolic responses can persist long after the cessation of status epilepticus and that both increases and decreases in RCGU can be seen in acute limbic status epilepticus. PMID- 1745355 TI - Self-sustaining limbic status epilepticus. II. Role of hippocampal commissures in metabolic responses. AB - In prior work, we developed a model of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation (CHS). Previous electrographic studies showed that SSLSE was synchronized between the cerebral hemispheres. On the basis of this initial work, we postulated that hippocampal commissures were critical for the initiation and maintenance of SSLSE. In the current experiments, we tested this hypothesis by applying CHS in animals with (CMX) or without (-CMX) hippocampal commissurotomies. In the -CMX group, electrographic SSLSE was synchronized between the stimulated and contralateral sides. In the CMX group, SSLSE developed only on the stimulated sides. Regional cerebral glucose utilization (RCGU) was also studied acutely (1 hour) after CHS using 2-deoxyglucose autoradiography. In the -CMX group, there was symmetrically increased RCGU in the hippocampus, retrohippocampal structures, and associated limbic and subcortical nonlimbic regions. In the CMX group, a similar pattern was found, but confined to the side of stimulation. CMX alone did not change RCGU values from those in control (-CMX, nonstimulated) brain in any of the regions studied. Areas of bilateral neocortical hypometabolism were found in both (CMX and -CMX) SSLSE groups. These results lead to rejection of the hypothesis that hippocampal commissures play an essential role in the initiation and maintenance of SSLSE. Instead, a feedback circuit involving the hippocampus and its adjacent structures seems to be the critical anatomic substrate for SSLSE. The presence of neocortical hypometabolism after CMX indicates that the structures other than the hippocampal commissure (eg, the thalamus or other forebrain commissures) mediate this effect. PMID- 1745356 TI - Changes in muscle sympathetic nerve activity during sleep in humans. AB - We microneurographically recorded muscle sympathetic nerve activity (MSA) during sleep in 12 healthy volunteers while simultaneously recording EEG, EOG, ECG, respiration, and blood pressure and determined the number of pulse-synchronous MSA bursts per minute (burst rate) for non-rapid eye movement (nonREM) sleep and rapid eye movement (REM) sleep. MSA decreased during nonREM sleep with progressively deeper sleep stages. During REM sleep, the burst rate of MSA increased and was associated with marked fluctuations in arterial blood pressure. During sleep stage 2, MSA bursts occurred approximately 1 second after spontaneous K-complexes. We conclude that (1) the decreases in MSA during nonREM sleep stages may indicate sleep-stage dependent central suppression of MSA activity; (2) increases in MSA during REM sleep suggest instability of the autonomic nervous system; and (3) a common pathway may exist for MSA bursts and K complexes. PMID- 1745357 TI - The effect of stimulus rate upon common peroneal, posterior tibial, and sural nerve somatosensory evoked potentials. AB - We examined the effect of stimulus rate on somatosensory evoked potentials (SEPs) following stimulation of the common peroneal nerve (CPN) at the knee, and the posterior tibial nerve (PTN) and sural nerve (SN) at the ankle. We measured the amplitude of P40-N50 and N50-P60 in the PTN-SEP and corresponding amplitude of CPN-SEP and SN-SEP at the rate of 2.3, 3.4, 4.1, and 5.1 Hz. When the stimulation rate was increased from 2.3 to 5.1 Hz, the P40-N50 amplitude decreased by 50% for the CPN-SEP and 20% for the PTN-SEP. Also, the N50-P60 amplitude was reduced by 30% in the CPN-SEP and 20% in the PTN-SEP. In contrast, this change in stimulus rate produced no significant amplitude decline in the SN-SEP. Blocking the peroneal nerve with lidocaine just distal to the stimulating electrodes eliminated the descending peroneal nerve volley and abolished the amplitude attenuation observed with the faster stimulus rate. The findings suggest that at higher rates of stimulation, the afferent volleys induced by the movements that follow mixed nerve stimulation interfere with the SEP produced by electrical activation of the sensory afferents. The interference is greater when the more proximal site of the mixed nerve is stimulated. PMID- 1745358 TI - Progressive depletion of fast alpha-actinin-positive muscle fibers in Duchenne muscular dystrophy. AB - In normal human muscle, a monoclonal antibody against alpha-actinin recognizes an isoform that is only expressed in a population of fast fibers histochemically identified as type IIb or fast-twitch glycolytic. Immunohistochemical studies of muscle biopsies from patients with Duchenne muscular dystrophy (DMD) showed that the number of alpha-actinin-positive type IIb fibers was essentially normal in preclinical patients. Symptomatic patients between the ages of 3 and 5 years showed depletion of these fibers, which were not seen in patients older than 5 years. ATPase histochemistry showed that a few type IIb fibers were present in muscle from symptomatic DMD patients but lacked the fast isoform of alpha actinin. The data suggest that type IIb fibers are affected early in DMD. PMID- 1745359 TI - Is essential tremor benign? AB - We analyzed the results of the Sickness Impact Profile, a self-reporting measure of sickness-related dysfunction in 753 essential tremor (ET) patients, 87 controls from the general population, and 145 patients with Parkinson's disease (PD). Compared with the general population, ET patients had significantly greater dysfunction in all but one category. Communication, Work, Emotional Behavior, Home Management, and Recreation and Pastimes were particularly impaired in ET. The PD patients had significantly higher dysfunction in all categories as compared with ET patients. We conclude that significant disability can occur in ET and, compared with PD, ET tends to be less severe but causes relatively greater psychosocial dysfunction. PMID- 1745360 TI - Exacerbation of Gilles de la Tourette's syndrome associated with thermal stress: a family study. AB - Gilles de la Tourette's syndrome (TS) is a familial disorder that is often exacerbated by stress or fatigue. Here we present a family of a TS proband that has several members with obsessive-compulsive symptoms, a bleeding disorder, and an unusual sensitivity to heat. The proband, who is affected by all of these traits, was challenged with heat or exercise in climate-controlled conditions and showed a marked increase in the frequency of tics. PMID- 1745361 TI - Superficial siderosis of the spinal cord: a rare cause of myelopathy diagnosed by MRI. AB - Repeated bleeding into CSF spaces may cause superficial siderosis with progressive neurologic impairment. The unique physical properties of MRI provide a basis for the in vivo diagnosis of this entity. PMID- 1745362 TI - HTLV-I-associated myelopathy: clinicopathologic correlation with localization of provirus to spinal cord. AB - A 49-year-old South African man developed a rapidly progressive myelopathy 14 months after blood transfusion and died 1 year after the onset of symptoms. Detailed pathologic examination of the spinal cord was consistent with the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although no HTLV-I viral particles, antigens, or nucleic acids were detected in situ, polymerase chain reaction assays revealed HTLV-I proviral DNA in cervical, thoracic, and lumbar levels of the spinal cord, with the greatest amount being detected at the thoracic level. These findings suggest that the pathogenesis of HAM/TSP depends on direct infection of neural or immune elements within the spinal cord. PMID- 1745363 TI - Granulomatous amebic encephalitis in an AIDS patient. AB - A 39-year-old man with AIDS died after developing a variety of neurologic symptoms and signs. CT showed multiple enhancing lesions in the cerebral hemispheres and cerebellum. Postmortem examination revealed parenchymal hemorrhagic and necrotizing lesions with a thrombo-occlusive vasculitis due to Acanthamoeba, which was typed as Acanthamoeba group 2, probably A rhysodes, by immunofluorescence. PMID- 1745364 TI - EMG spectral shift- and 31P-NMR-determined intracellular pH in fatigued human biceps brachii muscle. AB - We have simultaneously recorded human biceps brachii intracellular pH, estimated by 31P-NMR, and EMG spectral shift, during isometric contraction and recovery in six subjects. This method allows us to concurrently study several components of muscle fatigue. The results show a clear dissociation between the recovery of intracellular pH, force-generating capacity, and the shift to low frequency of the EMG power spectrum induced by fatiguing exercise. PMID- 1745365 TI - Ipsilateral neglect in a patient following a unilateral frontal lesion. AB - Using a crossed-response task, it has been demonstrated that as a patient with unilateral frontal lesion recovers from visual inattention, he or she may inappropriately saccade to contralateral stimuli (visual grasp). We report a patient with a right frontal lesion who showed a similar phenomenon on sequential line bisection tasks. On day 1, he showed left-sided neglect on line bisections that enhanced with sequential trials. On day 5, he exhibited right-sided neglect (ipsilateral neglect) on line bisection tasks that also enhanced with repeated trials. PMID- 1745366 TI - Contribution of concurrent Doppler and EEG in differentiating occipital epileptic discharges from migraine. AB - In a young woman, episodes of visual symptoms were accompanied by simultaneous nonspecific EEG alterations. Concurrent Doppler sonography showed increased blood flow velocity with latency of a few seconds in the posterior cerebral arteries only. This is typical for local autoregulatory hyperperfusion due to increased neuronal activity, thus indicating focal epileptic discharges and excluding migrainous attacks. PMID- 1745367 TI - Truncal asterixis associated with ceftazidime, a third-generation cephalosporin. PMID- 1745368 TI - Factitious status epilepticus as a particular form of Munchausen's syndrome. PMID- 1745369 TI - Glucose and infarct size. PMID- 1745370 TI - Erythrocyte transketolase. PMID- 1745371 TI - HLA expression in myoblasts. PMID- 1745372 TI - [Informatics in medicine: drug monitoring in the elderly. Software for clinical procedures]. AB - The Author describes the main procedure for the clinical control of pharmacokinetics and therapeutical programmes in medical practice, taking the use of digitalic alkaloids as an example. The procedure entails: a) Data records: this comprises a system for loading the patient's data into three different structures. The first record contains general information regarding the patient and it is used independently during the therapeutic regimen selection phase. The second record contains details of previous therapy, while the third concerns the input of digitalemic vales. b) The programme: it elaborates the main pharmacokinetic constants (Ka, Kcp, Kpc, Kslope, VC) of the predicted two compartment model and Sheiner's expression is used to correct it for the reference statistical population. c) Distribution values in the compartments: the chapter illustrates the mean values of alkaloid tissue distribution in normal subjects, the mean value of digoxin with protein binding, the importance of circulating pharmacological ranges and the digitalisation load in relation to tissue deposits. d) Print-out: this represents the observation and therapy selection phase. A typical example of digoxin therapy is illustrated using a dot matrix plotter and the methods are discussed for interpreting the results of this print-out. PMID- 1745373 TI - [Immune reaction in von Recklinghausen's neurofibromatosis]. AB - A multidisciplinary study was performed on cases of neurofibromatosis to highlight the immunological reaction using broad-spectrum hematic tests and multiphase evaluation together with clinical and instrumental monitoring. The aim of the study was to focus attention on this rare disease and prompt further sequential immunological studies. A greater knowledge of the disease would allow the promising potential of new drugs to be exploited, in particular selective immunomodulatory drugs, in the hope of controlling the symptoms of disease (and overcoming further obstacles to the surgical removal of any neurofibromas that the patient wishes. PMID- 1745374 TI - [Prognostic value of serum immunoglobulins in patients with hepatic cirrhosis]. AB - Immunoglobulin (Ig) serum levels have been assayed in 729 patients with liver cirrhosis of different etiologies, in order to evaluate their prognostic value. Serum levels of three classes of Ig resulted mainly elevated in the three etiological groups (post-hepatitic, post-alcoholic, cryptogenetic) and they were significantly related to the severity of the liver disease, evaluated according to the Child-Turcotte score. The computerized analysis of the survival curves of patients with IgG, IgM, IgA values normal or elevated demonstrated an adverse prognostic rate in those with elevated Ig values. The difference among the survival curves, compared by the Lee-Desu method, was statistically significant (p less than 0.001). Our data suggest that the Ig levels can be considered as a prognostic index in liver cirrhosis patients. PMID- 1745375 TI - [Cefixime. Microbiologic, kinetic and clinical profile]. AB - The microbiological, kinetic and clinical profile of cefixime, a IIIrd generation cephalosporin, administered orally, is presented. Cefixime is highly active versus Gram-negative aerobic bacteria while, with respect to Gram-positive bacteria, it is only active against Str. pneumoniae, Str. pyogenes, Str. agalactiae, and Str. bovis. It has no action against anaerobics. Endowed with good kinetics, cefixime possesses a favourable tissue distribution. Cefixime is highly indicated in infections of the upper and lower airways where the aethiology is prevalently due to Str. pneumoniae, H. influenzae and B. catarrhalis, that are extremely sensitive to the antibiotic. It is concluded that the therapeutic armamentarium has been enriched by a new, highly active antibiotic that, administered in a monodese/die, ca satisfy patient compliance. PMID- 1745376 TI - [Comparison of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids and index of cardiovascular risk in diabetics with dyslipidemia]. AB - Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate. PMID- 1745377 TI - [The heart, the elderly, and diabetes mellitus. Epidemiologic study of 333 ambulatory clinical cases]. AB - The paper proposes a new classification to describe the normal senile heart and its pathological forms: "small aortic heart" (nonhypertrophic-dilatative myocardiopathy and its ischemic form) and "large aortic heart" (hypertrophic dilatative myocardiopathy and its ischemic form). The statistical distribution of 241 elderly patients with diabetes mellitus using this classification was compared to a control group of 92 elderly non-diabetic subjects. The results reveal the significant epidemiological incidence of ischemic cardiopathy with small aortic heart in diabetic patients compared to the control group in which more ischemic hypertrophic-dilatative cardiopathies were present. This observation supports the hypothesis that senile diabetic cardiopathy begins with a metabolic block with reduced contractile energy, and the overlying important ischemic component leads to the development of the small-size clinical phenotype. PMID- 1745378 TI - [Mortality and HIV infection in a group of intravenous heroin addicts from 1985 to 1989]. AB - One hundred and eighty-seven heroin addicts resident in Valle Seriana Superiore were monitored from July 1985 to July 1989. This sample was representative of a total population of drug addicts estimated at some 350 subjects, 90 of whom (48.1%) were HIV-positive in Elisa assays and Western blot control tests. Six patients (3.2%) died; 3 of whom (3%) were HIV-positive and 3 (3.3%) were HIVab negative. The most frequent cause of death (59%) was heroin overdose, which occurred in both HIV-positive and negative subjects, showing that the fear of contracting the disease or its possible evolution is not a deterrent in modifying risk behaviour. During the four years of the study, 5 (5.5%) of the HIV-positive patients developed confirmed AIDS. Only one patient died from AIDS, thus confirming the current risk of death as being 1.1% in seropositive patients. An increase in mortality due to AIDS is expected in the future, in line with the current prevalent mortality rate due to heroin overdose. PMID- 1745379 TI - [Cutaneous tumor metastasis. A possible first clinical event of visceral neoplasms]. AB - Two cases of visceral malignant tumours due to cutaneous metastases (stomach adenocarcinoma and left pulmonary adenocarcinoma). Are reported in both cases the cutaneous lesions represent the first clinical phenomenon of the disease. PMID- 1745380 TI - [Complete endocardial cushion defect and bone malformations of the hands. Holt Oram syndrome]. AB - A 44 year old woman with upper limb skeletal malformations and endocardial cushion defect is described. This congenital heart disease was rarely reported in association with Holt-Oram syndrome. PMID- 1745381 TI - [Topical therapy with beta-interferon in a case of neoplastic pleuro-pericardial effusion]. PMID- 1745382 TI - [Marked hematic hypereosinophilia caused by Giardia Lamblia infestation in a subject with Churg-Strauss syndrome]. AB - We report a Churg-Strauss syndrome case complicated by Giardia Lamblia infection which increased markedly the number of blood eosinophils with appearance of eosinophils able to form rosettes with unsensitized sheep red blood cells. Metronidazolo therapy reduces markedly the blood hypereosinophilia. The strong relationship between blood hypereosinophilia and Giardia Lamblia in this patient, suggests that there is an interaction between different eosinophilopoietic stimuli. PMID- 1745383 TI - Insights into the complex aluminium and iron relationship. PMID- 1745384 TI - Amelioration of gentamicin nephrotoxicity by phospholipids. AB - The effect of phospholipids on gentamicin-induced nephrotoxicity was studied in Sprague-Dawley rats. Group 1a (5 rats) were given daily intraperitoneal injections of 100 mg/kg of gentamicin and sacrificed on day 7. Group 1b (10 rats) were similarly treated but were sacrificed on day 14. Group 2a (5 rats) were given 30 mg/kg of phospholipids for 6 days and sacrificed on day 7, serving as phospholipid controls. Group 2b (5 rats) were similarly treated, and from day 7 onwards daily intraperitoneal injections of 100 mg/kg of gentamicin were given while oral phospholipids were continued until the rats were sacrificed 7 days after gentamicin treatment. Group 2c (10 rats) were treated in the same manner as group 2b but the animals were sacrificed on day 28 after gentamicin treatment. Group 3 (10 rats) were given 30 mg/kg of phospholipids concurrently with intraperitoneal gentamicin injections and were sacrificed on day 28. Protein concentrations, N-acetyl-beta-glucosaminidase (NAG) activities and creatinine were measured in 24-h urine samples. Serum creatinine concentrations were measured in blood samples and 24-h creatinine clearance calculated. Gentamicin concentrations were determined in kidney tissues from which sections were also taken for light- and electron-microscopy. Results showed that gentamicin induced a marked increase in NAG and protein excretion, and a marked decrease in creatinine clearance with six rats succumbing to uraemia. Phospholipid treatment, whether started before or concurrently with gentamicin injections, reduced gentamicin-induced nephrotoxicity. The rats did not lose weight. Urinary excretion of NAG and protein was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745385 TI - Experimental gold-induced autoimmunity. AB - The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity. PMID- 1745386 TI - The reflex control of vasopressin in haemodialysis patients. AB - We studied the reflex arginine vasopressin (AVP) response to hypotensive, isosmotic fluid subtraction (by isolated UF) in 14 uraemic patients on renal dialysis treatment: five with normal autonomic function and nine with autonomic involvement of various degrees. Fluid subtraction caused a comparable mean arterial pressure (MAP) decrease in the two groups. The reduction in right atrial pressure was inversely related with the severity of autonomic neuropathy (rs = 0.72, P = 0.004), being distinctly attenuated in the second group (P = 0.006). Plasma arginine vasopressin increased similarly in patients with normal autonomic function and in those with autonomic involvement. The response of patients with haemodialysis hypotension was similar to that of other patients. Reflex control of arginine vasopressin is preserved even in the presence of afferent/central neuropathy or more advanced, widespread autonomic damage in uraemic man. The data suggest that it is unlikely that altered release of arginine vasopressin is involved in the pathogenesis of haemodialysis hypotension. PMID- 1745387 TI - Iron uptake in aluminium overload: in vivo and in vitro studies. AB - In this study we have evaluated the haematological consequences of chronic aluminium (Al) overload. We have also investigated 'in vivo' whether aluminium overload may modulate gastrointestinal iron (Fe) absorption and 'in vitro' whether the presence of aluminium may influence the cellular uptake of iron. The in vivo studies were performed in rats with normal renal function and the in vitro experiments were done using the rat intestinal epithelial cell line RIE-1. The results demonstrate that aluminium deposit in tissues even with normal renal function. The intraperitoneal aluminium loading resulted in serum and tissue aluminium increases comparable with concentrations found in aluminium-intoxicated renal patients. The aluminium intoxication was accompanied by a microcytic anaemia with a haematological pattern similar to that observed in iron-deficiency anaemia. Nevertheless, iron absorption was significantly reduced despite an increased total iron binding capacity (TIBC). In addition, aluminium was also able to reduce in vitro cellular uptake of iron in the RIE-1 intestinal cell line. These experimental results demonstrate that aluminium interferes with iron absorption and iron transfer, and suggest that these mechanisms may be responsible for maintaining and even increasing the anaemia observed in aluminium overload. PMID- 1745388 TI - Epidemiology of CAPD-associated peritonitis caused by coagulase-negative staphylococci: comparison of strains isolated from hands, abdominal Tenckhoff catheter exit site and peritoneal fluid. AB - We identified twenty patients maintained on continuous ambulatory peritoneal dialysis who suffered repeated episodes of peritonitis caused by coagulase negative staphylococci. We documented hand and exist-site coagulase-negative staphylococcus-associated peritonitis over a total period of 32 months, and compared hand and exit-site strains with strains isolated from dialysate fluid using three typing methods: biotyping using the API Staph kit plus antibiograms, immunoblotting using sera raised in rabbits to three standard strains of coagulase-negative staphylococci, and 35S-methionine-labelled coagulase-negative staphylococcal profiles separated on sodium dodecylsulphate polyacrylamide gel electrophoresis and visualised by autoradiography (radioPAGE). In 5 of 84 episodes, strains isolated from skin were indistinguishable by all three typing methods from the dialysate strain. In a further two episodes, hand or exit-site isolates were indistinguishable by all three typing methods from the dialysate strain isolated in the subsequent, but not the same, episode. Thus in the majority of episodes, no inference of hand or exit-site origin of dialysate infection could be drawn. PMID- 1745389 TI - Ocular complications in renal allograft recipients. AB - Ocular complications in renal allograft recipients are a significant cause of morbidity. Of 80 renal transplant recipients, 42 (52.5%) developed ocular complications. These included posterior subcapsular cataract in 22 patients (27.5%), opportunistic ocular infections by CMV, cryptococcus, mucormycosis, herpes simplex and herpes zoster in five (6.25%), steroid-induced raised intraocular pressure in four (5%) and primary disease-related vascular complications in ten (12.5%). Our findings highlight the importance of regular ocular examination of all allograft recipients in the post-transplant period. PMID- 1745390 TI - Rhinocerebral mucormycosis in haemodialysis patients treated with desferrioxamine: possible role of recent surgery as an additional risk factor. PMID- 1745391 TI - Chylous ascites and continuous ambulatory peritoneal dialysis. PMID- 1745392 TI - Arachidonate cyclo-oxygenase and lipoxygenase products in the mediation of glomerular immune injury. PMID- 1745393 TI - Late leaks in peritoneal dialysis patients. AB - A series of eight patients with leakage of dialysate around the exit site of their peritoneal dialysis catheters is reviewed. In all cases the leak occurred at least 1 month after catheter placement. There were no risk factors allowing prediction of leakage. Four cases required surgical intervention, and all patients returned to CAPD. PMID- 1745394 TI - Aluminium uptake by intestinal cells: effect of iron status and precomplexation. AB - The investigation of different aluminium-binding agents and metabolic conditions that might act as critical factors in modulating aluminium absorption could yield valuable information in the understanding of aluminium gastrointestinal absorption. We evaluated the effect of iron depletion in aluminium uptake and the role of transferrin and citrate in aluminium incorporation by the intestinal epithelial cell line RIE1. Both complex, aluminium-citrate and aluminium transferrin were prepared in a molar ratio of 2:1; both facilitated the aluminium uptake although a greater aluminium incorporation was found when aluminium was administered as aluminium-transferrin. This difference became even greater in the iron-depleted cells (normal cells vs iron-depleted cells): 7.7 +/- 1.4 versus 30 +/- 5.6 ng Al/micrograms DNA (P less than 0.05). From these and previous data it is possible to speculate that iron status could modulate the intestinal uptake of aluminium and that both transferrin and citrate would act as effective carriers in the incorporation of aluminium into mucosal cells. PMID- 1745395 TI - Erythrocytosis after renal transplantation. PMID- 1745396 TI - Polyvalent immunoglobulins in sensitised renal transplant recipients. PMID- 1745397 TI - Sympathetic innervation of the male feline urethral rhabdosphincter. AB - Sympathetic innervation of the male feline urethral rhabdosphincter was investigated by means of electromyography (EMG). Hypogastric nerve stimulation elicited responses in the rhabdosphincter, the latencies and amplitudes ranged from 40 to 107 ms and 6 to 40 microV, respectively. These hypogastric nerve evoked responses in the rhabdosphincter were not affected by whether the urinary bladder was empty or full. The results suggest that hypogastric nerve-evoked responses in the rhabdosphincter are not dependent on somatic nerve, but are produced through a rather direct effect of sympathetic nerve on the rhabdosphincter. PMID- 1745398 TI - Blockade of 5-HT2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat. AB - The effects of the 5-HT2 receptor antagonists pirenperone, cinanserin and ritanserin on impairment of working memory in an animal model of cerebral ischemia were investigated, using a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the 3 panel gates at 4 choice points). Pirenperone at 0.32 and 1.0 mg/kg, cinanserin 10 mg/kg and ritanserin 3.2 mg/kg administered i.p. immediately after blood flow reperfusion significantly reduced the increase in errors expected to occur 24 h after the 5 min of ischemia. These results suggest that the blockade of 5-HT2 receptors prevents the impairment of working memory following transient forebrain ischemia. PMID- 1745399 TI - Frequency of occurrence of perforated synapses in developing rat neocortex. AB - The frequency of occurrence of perforated synapses in the molecular layer of rat parietal cortex has been determined using the disector method. Perforated and non perforated synapses were examined in electron micrographs, all quantitative procedures being carried out on adjacent sections, as required by the disector procedure. The numerical densities of perforated, non-perforated and all synapses were determined at nine ages, ranging from 0.5 to 22 months of age. The frequencies of perforated synapses were subsequently calculated. These ranged from 18.1% at 0.5 months to a peak of 37.2% at 10 months of age, and remained at around 34% up to 19 months. A frequency of 26.7% was found at 22 months of age. The mean projected height of the total perforation increased from 66 nm at 0.5 months to 133 nm at 22 months of age. These results suggest that perforated synapses are present throughout the life-span of the animal, and increase in complexity with increasing age. PMID- 1745400 TI - Electrical stimulation of visceral afferent pathways in the pelvic nerve increases c-fos in the rat lumbosacral spinal cord. AB - Electrical stimulation (20-35 Hz, 2-5 V, 1.5 h) of the pelvic nerve in urethane anesthetized rats increased the expression of c-fos protein-immunoreactivity primarily in neurons in the L6-S1 segments of the spinal cord. The neurons were localized to areas receiving afferent input from the pelvic viscera including the superficial dorsal horn, the dorsal commissure, and lateral laminae V-VII in the region of the sacral parasympathetic nucleus. These experiments indicate that (1) electrical stimulation of abdominal nerves following surgical exposure is a useful method for tracing visceral afferent pathways and (2) afferent information from the pelvic viscera is received by neurons in specific areas of the dorsal horn. PMID- 1745401 TI - Apomorphine induces ejaculation in chronic decerebrate rats. AB - Chronically maintained supracollicular decerebrate (CD) rats, but not rats with midthoracic (T10) spinal transections (SPI) or neurologically intact controls, displayed erection and ejaculation following systemic administration of the dopamine (DA) agonist, apomorphine (APO). The response was blocked by pretreatment with the DA receptor antagonist, cis-flupentixol. CD rats, like intact controls, failed to display erections or penile cupping in response to the same mechanical stimulation that elicited short-latency responses in SPI rats. The present results demonstrate excitatory and inhibitory mechanisms of relevance to the copulatory behavior of the male rat that are endemic to the caudal brainstem neurally isolated from forebrain influence. PMID- 1745402 TI - REM sleep-associated hemoglobin oxygenation in the monkey forebrain studied using near-infrared spectrophotometry. AB - The oxygenation state of hemoglobin (Hb) in the monkey forebrain was monitored continuously throughout nocturnal sleep using a near-infrared spectrophotometric technique. During rapid eye movement (REM) sleep, an increase in oxygenated Hb occurred concomitantly with a decrease in deoxygenated Hb, while no significant changes in Hb oxygenation were observed during slow wave sleep (SWS). A gradual increase in total Hb content was also observed to occur during each REM sleep episode but not during SWS. PMID- 1745403 TI - Sequential expression of JUN B, JUN D and FOS B proteins in rat spinal neurons: cascade of transcriptional operations during nociception. AB - Expression of the immediate-early gene encoded proteins JUN B, JUN D and FOS B was investigated by immunocytochemistry in rat L5 spinal cord up to 24 h following stimulation of hind limb somatosensory nociceptors by noxious heat or injection of formalin. In both experimental protocols, JUN B, which did not show basal expression, reached maximum expression after 2 h and thereafter slowly decreased. In contrast, the expression of JUN D, which was present before stimulation in many spinal neurons, was increased after 4 h, reached its maximum after 8 h and thereafter remained elevated. FOS B which was absent under basal conditions reached its maximum between 4 h and 8 h and thereafter declined but was still present after 24 h. All immunoreactivities were restricted to the ipsilateral dorsal horn except JUN D which was also induced in the contralateral side after 8 h. The results are discussed in respect to their meaning for transcriptional operations of JUN and FOS proteins. PMID- 1745404 TI - Synaptic effects in lumbar alpha-motoneurones evoked from group II muscle afferents via two different interneuronal pathways in the cat. AB - Conditioning of monosynaptic reflexes was used to investigate group II excitation from quadriceps (Q) and sartorius (Sart) in posterior biceps-semitendinosus (PBSt) motoneurones and different lesions were made to analyze the interneuronal pathways. The purpose of the investigation was to find if the excitation from group II Q and Sart afferents, which enter the spinal cord in L4-L6, is relayed to motoneurones by interneurones located in these segments and/or in the same segments (L7-S1) as the PBSt motoneurones. In some experiments a transection of the dorsal column in L6, which interrupts the group II input from Sart and Q to interneurones in the L7-S1 segments, resulted in a marked decrease (by about 2/3) of group II excitation from these nerves. In other experiments the same lesion did not reduce the group II effect. In the latter cases the effect could be abolished by a second lesion of the lateral funiculus (LF) in L5-L6. It is postulated that potent effects from Q and Sart group II afferents can be evoked by interneurones located in L7-S1, i.e. in the same segments as the PBSt motoneurones (L7-S1), and/or via interneurones in more rostral segments. The axons of the more rostrally located group II interneurones appear to descend mainly in the middle part of the LF. PMID- 1745405 TI - The effect of calcium channel antagonists on the release of [3H]noradrenaline in the human neuroblastoma, SH-SY5Y. AB - The effect of calcium channel antagonists on depolarization and carbachol evoked release of [3H]noradrenaline in the human neuroblastoma, SH-SY5Y, was investigated. Nifedipine, verapamil and diltiazem completely inhibited the depolarization evoked release of [3H]noradrenaline with IC50 values of 0.44 +/- 0.1 microM, 3.6 +/- 0.24 microM and 5.6 +/- 0.2 microM respectively. In addition, nickel, cobalt and cadmium, all at 2 mM, inhibited depolarization evoked release by 89.2 +/- 2.3%, 72.6 +/- 1.6% and 102.5 +/- 1.4% respectively. Furthermore, omega-conotoxin resulted in at least 20% inhibition of potassium evoked release, suggesting a role of N-type calcium channels. Carbachol evoked release of [3H]noradrenaline was inhibited by 10(-4) M nifedipine, diltiazem and verapamil by 15.6 +/- 1.1%, 14.6 +/- 3.2% and 23.6 +/- 1.8% respectively and by 2 mM nickel, cobalt and cadmium by 13.8 +/- 3.2%, 34 +/- 2.1% and 6.5 +/- 3.7% respectively. These results suggest that depolarization evoked release of [3H]noradrenaline is mediated via L- and N-type calcium channels, whereas, carbachol evoked release does not appear to be coupled an L-, T- or N-type voltage sensitive calcium channel. PMID- 1745406 TI - Excitability changes in C fibers of rat sciatic nerve following impulse activity. AB - Three phases in the oscillatory changes of both threshold and conduction velocity were identified following impulse activity in single C fibers of rat sciatic nerves. These after-oscillations, occurring after the refractory period, varied with the number and timing of preceding 'conditioning' impulses. The excitability changes differed both qualitatively and quantitatively among fibers, thus implying underlying variation among C fibers in the density and distribution of voltage-gated channels and ion pumps. PMID- 1745407 TI - Entorhinal neurofibrillary tangles in Alzheimer disease with Lewy bodies. AB - Entorhinal cortex is the major source of hippocampal afferents. Its neurons, especially in layer 2, develop neurofibrillary tangles (NFTs) in Alzheimer disease (AD). We quantified entorhinal NFTs in cases of AD, elderly controls, and in brains with both AD pathology and subcortical and neocortical Lewy bodies, (a Lewy body variant, LBV). A nosologic controversy hinges on whether LBVs are a form of AD or a different disease, since they have few neocortical NFTs and their neuritic plaques often lack paired helical filament immunoreactivity. The LBVs had more entorhinal NFTs than controls (P less than 0.001), but fewer than ADs (P less than 0.02), despite comparable numbers of neuritic plaques. AD pathology in LBVs is of moderate severity, or perhaps in an earlier developmental stage. PMID- 1745408 TI - Effect of repeated immobilization stress on the uptake of exogenous [3H]dopamine in adrenal chromaffin cells of mice. AB - Uptake of [3H]dopamine in adrenal chromaffin cells of the mouse during repeated immobilization was examined by autoradiography. Repeated daily immobilization of mice resulted in an increased uptake of [3H]dopamine to the level of denervated chromaffin cells. The increase was observed only in adrenaline-storing (A) cells, not in noradrenaline-storing (NA) cells. The results indicate that sympathetic outflow to the adrenal gland, especially to A cells, is ceased or blocked during the adaptation to stress. PMID- 1745409 TI - A high glucose environment improves survival of diabetic neurons in culture. AB - Dorsal root ganglia neurons from streptozotocin-induced diabetic and normal C57BL mice were cultured in serum-containing and serum-free media. The ratio of dead cells was higher in diabetic neurons than in controls in the early stages of culture. The effect of glucose concentration on survival in the culture medium was also measured for 1 week. Treatment with high glucose concentrations improved the survival of diabetic neurons, which was enhanced by duration of diabetes in the animal. These results indicate that exposure to hyperglycemia in vivo might adapt neurons to a high glucose environment in vitro. PMID- 1745410 TI - Ontogenesis of the axonal circuitry associated with the olfactory system of the rat embryo. AB - The prenatal development of axonal connections in the rat olfactory system was studied using DiI. On day 16 (E16), the olfactory and vomeronasal nerves extended from the olfactory epithelia to the olfactory bulb (OB), the terminal nerve to the telencephalic septum, while axons of mitral and tufted cells reached the anterior olfactory nucleus (AO). Axons from the AO were also seen in the anterior commissure. On day E16(8) (at 16 days, 8 h), axons were anterogradely followed from the dorsal OB through the lateral olfactory tract (lo) to the bed nucleus of the accessory olfactory tract. At E18(0), crystals implanted in the olfactory epithelium labeled the mitral cell layer and the lo. PMID- 1745411 TI - Specialized presynaptic dendrites in the stratum cellulare externum of the optic tectum of an elasmobranch, Scyliorhinus canicula L. AB - Electron microscopy of the stratum cellulare externum of the optic tectum of an elasmobranch revealed the presence of two types of presynaptic dendrites in the neuropil as well as axo-dendritic synapses. In the dendro-dendritic or dendro axonic synapses, the presynaptic process was a beaded dendrite. These findings support the view that the synaptic organization of the tectum in elasmobranchs is basically similar to that of higher vertebrates, rather than the classical opinion that it is less highly organized. PMID- 1745412 TI - Magnetoencephalographic 10-Hz rhythm from the human auditory cortex. AB - Spontaneous magnetoencephalographic activity was recorded with a 24-SQUID gradiometer over the lateral aspects of the head in 3 healthy adults. All subjects displayed 8-10 Hz rhythmic activity which was not affected by opening of the eyes but was occasionally dampened by auditory stimuli. The equivalent sources of the rhythm were in the supratemporal auditory cortex, and the activity may therefore represent 'idling' of the auditory cortex. Obviously each sensory projection cortex has its own local spontaneous rhythm. PMID- 1745413 TI - Elevated circulating tumor necrosis factor levels in Alzheimer's disease. AB - Recent investigations have demonstrated a local inflammatory response in Alzheimer's disease (AD), including microglia and cytokines. Levels of the cytokine tumor necrosis factor alpha (TNF-alpha) in sera from patients with AD and age-matched controls were measured by an enzyme-linked immunoassay and a cytotoxicity bioassay. Significantly elevated levels of TNF were found in AD sera compared to controls. Elevated circulating TNF may be derived from the local CNS inflammatory reaction in AD, and may account for some systemic manifestations of AD such as weight loss. Future studies may determine if, in the absence of complicating disorders which may elevate TNF, circulating TNF could be a marker of AD inflammatory activity. PMID- 1745415 TI - Women in organized medicine: side by side. PMID- 1745414 TI - AIDS issues. PMID- 1745416 TI - The athletic team physician's medical bag. AB - Physicians are called upon to provide sideline coverage for athletes, as well as to travel with the team. The physician must be equipped with tools to handle a wide array of problems. The bag's contents allow the physician to manage medical, surgical, and orthopedic problems. PMID- 1745417 TI - The sports preparticipation evaluation. AB - The best sports preparticipation program requires an initial comprehensive evaluation, interim care, central reporting, and an appropriate followup examination. The preparticipation examination, when properly carried out, can meet the needs of our adolescents. PMID- 1745418 TI - Children and sports medicine in the 1990s. AB - Sports participation is an opportunity for children of all ages to improve their fitness, level of maturation, and physical and psychologic condition. A primary physician can play a significant role in promoting enhanced physical fitness in the office or as a team doctor. PMID- 1745419 TI - Recreational sports and the weekend athlete. AB - It is important to design an exercise program that provides an adequate amount of activity to attain maximal benefits at the lowest risk to the participant. Permanent lifestyle changes in eating and activity habits should be included in the primary goals of all programs. PMID- 1745420 TI - Sports injuries in the female athlete. AB - Women are successfully participating in a variety of sports in increasing numbers, both recreationally and competitively. There are certain anatomic and physiologic differences between men and women that make each sex unique, but there also are multiple external factors that significantly influence athletic performance. The nature of injuries seems to be more sports-specific than gender specific. Even the increased susceptibility to overuse syndromes found in women may be reduced by increasing awareness and redefining conditioning and coaching techniques. Further epidemiologic studies of women's athletic injuries will be needed to better define injury patterns and to suggest preventive measures. PMID- 1745421 TI - Sports medicine for the diabetic athlete. AB - Exercise can be a useful therapy for patients with type II diabetes mellitus. Improvements in body composition, glucose tolerance, insulin sensitivity, cardiovascular profile, and psychological state are some benefits. The benefits of exercise will enrich the lives of diabetics. PMID- 1745422 TI - Exercise and arthritis in the 1990s. AB - Arthritis sufferers want to share in the benefits of exercise without increasing their pain. Too much physical activity can increase the inflammatory response in arthritic joints. Walking is the ideal form of exercise, as it is fun, simple to do, and beneficial. PMID- 1745423 TI - Update on sports nutrition. AB - Adequate nutrition is vital to peak athletic performance. Insufficient energy and fluids can hinder ability to compete. Physicians and dietitians must emphasize nutrition's importance to athletes. Sports nutrition follows the same principles as good nutrition. PMID- 1745424 TI - Anabolic steroids: performance enhancers? AB - Physicians must discourage steroid use in those who have not yet begun and must treat those patients already on anabolic steroids. Physicians cannot encourage anabolic steroid use by their patients or by themselves. Anabolic steroids are bad for the user. PMID- 1745425 TI - Doctors' notebook. PMID- 1745426 TI - Neurotoxins and degeneration in the central nervous system. AB - Numerous examples exist where neurotoxins have been shown to induce selective death of certain groups of nerve cells. While the peripheral nerves are particularly vulnerable, neurotoxins are also capable of generating models of the major degenerative disorders of the central nervous system: dementia of Alzheimer's type, Parkinsonism, and amyotrophic lateral sclerosis. Important organic toxins, in this context, include certain pyridines, amines, aminoacids, nitriles, hexacarbons, and sulphides. Inorganic toxins include free radicals and certain metals. Toxins may also be classified according to their origin- exogenous or endogenous. This review will not consider neurological damage that can result from exposure to alcohol, or neurological adverse reactions to medications. PMID- 1745427 TI - Delayed expression of neurotoxicity: the problem of silent damage. AB - A prolonged period of latency between toxic exposure and disease is a recognized phenomenon in oncology, but is a relatively new concept in neurotoxicology. Suggestions that exposure to neurotoxic compounds may be followed years or decades later by clinically evident neurological disease have received considerable anecdotal support but little empirical evidence. In recent years, evidence has emerged linking environmental factors to several neurodegenerative diseases, including amyotrophic lateral sclerosis and the Parkinsonism-dementia complex. While these diseases have not been definitively demonstrated to arise from exposure to toxins or toxicants, nevertheless the possibility exists that xenobiotic exposure could lead to neurological conditions possessing a period of clinical "silence" prior to expression. Detection of such damage using standard toxicology testing protocols poses a major challenge. Lessons learned from neurodegenerative diseases can be profitably applied to the study of the long term effects of xenobiotics on the brain and elucidation of the role of aging on the expression of neurotoxicity. PMID- 1745428 TI - Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives. AB - During the past quarter century biomedical scientists have begun to recognize the unique opportunities for studying disease etiology and mechanisms of pathogenesis in non-Western anthropological populations with focal, endemic diseases. Such natural experiments as they are called, are important paradigms for solving etiological and epidemiological problems of widespread medical significance, with an ultimate goal towards treatment and prevention. The systematic search for etiological factors and mechanisms of pathogenesis of neurodegenerative disorders is perhaps nowhere better exemplified than in the western Pacific. During the past three decades, the opportunistic and multidisciplinary study of hyperendemic foci of amyotrophic lateral sclerosis and parkinsonism-dementia which occur in different cultures, in different ecological zones and among genetically divergent populations have served as natural models that have had a major impact on our thinking and enhanced our understanding of these and other neurodegenerative disorders such as Alzheimer disease and the process of early neuronal aging. Our cross-disciplinary approach to these intriguing neurobiological problems and the accumulated epidemiological, genetic, cellular and molecular evidence strongly implicates environmental factors in their causation, specifically the role of aluminum and its interaction with calcium in neuronal degeneration. As a direct consequence of our studies in these Pacific populations, we have undertaken the long-term development of experimental models of neuronal degeneration, in an attempt to understand the cellular and molecular mechanisms by which these toxicants affect the central nervous system. Our experimental studies have resulted in the establishment of an aluminum-induced chronic myelopathy in rabbits and the development of neurofilamentous lesions after low-dose aluminum administration in cell culture. These studies clearly demonstrate the philosophy that chronic rather than acute experimental models of toxicity are necessary in order to enhance our understanding of human neurodegenerative disorders with long latency and slow progression. Finally, the ultimate significance of these Pacific paradigms may well depend on our ability to comprehensively evaluate and synthesize the growing body of relevant scientific data from other human disorders and from widely divergent academic fields, as well as our ability to recognize emerging new models in nature. PMID- 1745429 TI - Cancer and the dynamics of neurodegenerative processes. AB - The term neurodegenerative denotes a process rather than a state. In contrast, most research on such disorders, whether clinical or experimental, represents only a slice of time. Their progressive nature is mostly confined to speculation instead of being codified in research protocols. Research on cancer, also a degenerative disease, is much more often framed in terms of process. Part of the difference is accounted for by the impact of quantitative modeling, which enjoys a long history in both basic and clinical cancer research and which originated in attempts to describe and understand tumor development. Analogous questions are posed by neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Among the issues that modeling could help to clarify are the properties and sources of the age-specific incidence rate, which resembles that for cancer, and the pharmacokinetics governing the toxic products of neurotransmitter metabolism. Neurodegenerative disorders maintain a research advantage because functional measures, mostly inaccessible to cancer investigators, serve as the ultimate index of progression. Their exploitation, however, in longitudinal studies remains inadequate. PMID- 1745430 TI - A pilot study of occupational and environmental risk factors for Parkinson's disease. AB - Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study. PMID- 1745431 TI - Longterm neurological complications of chronic, habitual cocaine abuse. AB - We review and expand the results of several previously published studies on computed tomographic and electroencephalographic correlates of chronic, habitual cocaine abuse in order to present a complete spectrum of the longterm neurological complications of cocaine abuse. We argue that prolonged and frequent cocaine abuse leads to biochemical and vascular cerebral insults that eventually may cause functional and structural abnormalities affecting predominantly the fronto-temporal areas. PMID- 1745432 TI - Animal test systems to study behavioral dysfunctions of neurodegenerative disorders. AB - The Eighth International Neurotoxicology Conference, Role of Toxicants in Neurological Disorders (1990), evaluated the evidence that chemical exposures may play a role in the development of neurodegenerative disorders. This article describes the major neurodegenerative disorders (Amyotrophic Lateral Sclerosis, Huntington disease, Parkinson disease, and Alzheimer disease) addressed at the conference, followed by a description of test systems or models developed to study behavioral aspects of these disorders in animals. However, due to the complexity of the disorders and the species in which they are found, fully developed models in animals of neurodegenerative disorders are lacking. This suggests the need for a clear strategy for selecting behavioral tests in animals to study aspects of any neurodegenerative disorders. Such a strategy is here exemplified for Alzheimer disease (AD) as a prototypical neurodegenerative disorder. Since an animal model cannot provide the full range of effects of human neurodegenerative diseases, particularly AD which produces incompletely characterized cognitive deficits, a rodent model must at this time be drawn from multiple sources, including: (1) Tests currently used to identify in rodents deficits associated with AD; (2) tests to identify Alzheimer-related signs in patients; and, (3) tests that relate to theoretical constructs of human and animal cognition. A battery that draws from those sources could include tests of: (a) Spatial learning and memory (Morris Water Maze and Radial Arm Maze), (b) delayed recall match-to-sample; (c) serial response learning; and, (d) visual discrimination (e.g., vertical vs. horizontal stimuli). This battery will identify behavioral changes characteristic of early-, middle- and late-stage AD, afford the potential to relate the findings to theoretical constructs of cognition, and evaluate learning capabilities not previously studied in rodent models of neurodegenerative disorders. PMID- 1745433 TI - Potentiation in the neurotoxic induction of experimental chronic neurodegenerative disorders: N-butyl benzenesulfonamide and aluminum chloride. AB - Repeated monthly intracisternal inoculations of N-butyl benzenesulfonamide induced a chronic, slowly progressive myelopathy in young adult New Zealand white rabbits that was manifested by hyperreflexia, spasticity, hypertonia, gait impairment and altered tonic immobility responses. The neuropathological features consisted of scattered neuroaxonal spheroids, fusiform distention of the intramedullary portions of the spinal cord ventral roots and, as defined by microtubule-associated protein-2 (MAP 2) immunoreactivity, an initial distention and subsequent loss of dendritic processes in neurons of the nucleus motoris lateralis with the perikaryon of these cells remaining intact. A similar chronic progressive myelopathy was induced by repeated low dose intracisternal inoculations of aluminum chloride in New Zealand white rabbits. However, the neuropathological changes were more extensive and consisted of dendritic, axonal and perikaryal inclusions of phosphorylated and nonphosphorylated neurofilament localized to spinal motor neurons in the nucleus motoris medialis, substantia grisea intermedia and select brainstem nuclei with only minimal involvement of the nucleus motoris lateralis. The co-administration of these two neurotoxins over the course of 8 months induced striking behavioral changes as well as a fulminant myelopathy. This was accompanied by a loss of neuronal perikarya in the nucleus motoris accompanied by a loss of neuronal perikarya in the nucleus motoris lateralis and topographically extensive neocortical neurofilamentous degeneration. These features suggest that potentiation occurs when the two toxins are co-administered, a view supported by an estimation of the co-neurotoxicity coefficient (CNC greater than 1). Our results have implications for understanding human neurodegenerative disorders in which potentiation of insults may occur, producing a clinical and neuropathological disease state not expected from either agent alone. PMID- 1745434 TI - Anatomical and behavioral sequelae of fetal brain transplants in rats with trimethyltin-induced neurodegeneration. AB - The effect of transplants of either fetal hippocampal or dorsal ventricular ridge (DVR) tissue into the brains of adult male rats exposed to TMT was determined for two behavioral tasks. Administration of TMT produced deficits in acquisition and performance of an operant differential reinforcement of low response rates (DRL) schedule and learning in the Morris water maze. The fetal transplants developed well within the TMT-damaged brains of the adult rats and numerous axons could be shown to cross the host-transplant interface. The transplants significantly reduced the DRL deficit produced by exposure to TMT. However, the TMT-induced deficit in water maze acquisition was made significantly worse by the hippocampal transplants. The improvement in DRL performance is attributed to the effect on the host brain of an unidentified trophic substance produced by the transplants. However, this positive effect may not protect the brain sufficiently to produce recovery in tasks demanding more complex neural computations than are required to withhold lever-press responses. The transplant-induced deficit observed in some aspects of water maze acquisition and performance may be attributable to either a tumor-like deleterious effect of the mass of the transplant or to abnormal neuronal activity transmitted from the transplant to the host brain. The results of the present study, and those from other similar studies, suggest that transplants of fetal tissue may be useful in producing changes in the brain of an animal exposed to an environmental neurotoxin, but that research should be focused upon development of transplant methodology that will minimize adverse effects of the grafts. PMID- 1745435 TI - Impaired tunnel-maze behavior in rats with sensory lesions: vestibular and auditory systems. AB - Maze behavior of rodents provides insight into processes of learning and memory and also serves to assess cognitive functions in neurotoxicity tests. Neurotoxic agents may impair maze behavior by acting upon different parts of the nervous system. To assess the dependence of maze learning upon vestibular and/or auditory input, the two systems were lesioned. Daily treatment of rat pups with streptomycin (400 mg/kg sc) on postnatal day 11 to 22 caused irreversible impairment of vestibular and auditory functions, whereas, 20 injections of neomycin in adult rats (100 mg/kg sc, postnatal weeks 8 to 11) led to hearing loss only. Hearing loss was assessed by absence of Preyer's reflex and impaired vestibular function by loss or shortened duration of postrotatory nystagmus. Learning in the unbaited 6-arm radial maze was tested at the age of 2 to 3 mon using a maze configuration that allowed to assess order of arm entries ("working memory") and left-right discrimination within each arm ("reference memory"). Treatment with streptomycin but not with neomycin led to impaired order of arm entries. Since treatment with streptomycin failed to induce any signs of brain lesions, impaired maze learning is considered to result from destruction of vestibular hair cell receptors with subsequent vestibular impairment and not from hearing loss or cognitive impairment. PMID- 1745436 TI - In vitro use of Schwann cells to elucidate neurotoxic injury. AB - Schwann cells are responsible for the maintenance of the peripheral myelin sheath and neurotoxic insult directed against these cells can result in demyelination with a concomitant loss of neural function. We have utilized several in vitro techniques to investigate the effects of neurotoxins on the complex interactions between SC and axons. SC may be isolated from fresh neonatal sciatic nerves and used to examine the effect of neurotoxins on the axonal membrane induction of SC proliferation and specific myelin protein mRNA expression. We have recently devised a method to obtain SC from frozen sciatic nerves. This method allows pooling of neonatal nerves to generate enough cells for subsequent study. We have also transfected primary Schwann cells with a plasmid containing the large T antigen to obtain a SC line suitable for neurotoxicology studies. The functional status of cultured SC may also be studied via expression of SC specific antigens such as glial fibrillary acidic protein, CNPase, S100, laminin, P0 and myelin basic protein. We also propose culturing SC with dorsal root ganglion neurons to investigate the effect of neurotoxins on all stages of SC maturation, from proliferation to the in vitro synthesis of a compact myelin sheath. These strategies will allow us to investigate the cellular mechanisms of neurotoxicity in the PNS. PMID- 1745437 TI - New opportunities with neuronal cultures to study the mechanisms of neurotoxic injuries. AB - Clonal lines of murine neuroblastoma (NBP2) and rat glioma (C6) were used to investigate the effects of methylmercuric chloride (CH3HgCl). Glioma cells were more sensitive to CH3HgCl than NB cells on the criterion of growth inhibition, but these cells were equally sensitive to inorganic mercury (HgCl1), Tri-n-butyl lead acetate and acrylamide on the same criterion. Alpha-tocopherol, alpha tocopheryl++ succinate and inhibitors of cAMP phosphodiesterase protected glioma cells against the growth-inhibitory effect of CH3HgCl, but they failed to protect NB cells in culture. Glioma factors, sodium ascorbate, non-inhibitory concentrations of prostaglandins E1 (PGE1), and glutamate enhanced the growth inhibitory effect of CH3HgCl on both NB and glioma cells in culture. The levels of certain specific cAMP-dependent and -independent protein phosphorylations appear to be very sensitive to CH3HgCl, and can be altered in both cell types by concentrations of CH3HgCl which do not affect growth or morphology of these cells. PMID- 1745438 TI - Nutrition, neurotoxicants and age-related neurodegeneration. AB - The National Institute on Aging supports a program of investigation of "biomarkers" of aging (biological parameters that change in magnitude with age), some of which may be among the, as yet unknown, causes of Alzheimer's disease. Exposure to neurotoxicants can also produce symptoms similar to Alzheimer's disease and has been proposed as a causative factor. We have examined the role of dietary factors and age on Alzheimer's disease-like neurohistological and behavioral symptoms as well as on the neurochemical effects of treatment with a prototypical neurotoxicant, trimethyltin (TMT). We found that aging greatly increased the susceptibility of hippocampal neurons to TMT-induced neurodegeneration. Limiting the dietary intake of calories, which has been reported to slow the aging process, also reduced the neurotoxic effects of a given dose of TMT. Our current research focuses on the use of neurotoxins to model neurodegenerative conditions of aging in animals. We propose that by identifying an age-amplified biomarker or biomarkers somewhere along the chain from neurotoxic stimulus to neuronal necrosis we may also discover an up- or down regulated gene, via it's gene product, that contributes to the etiology of human dementias. Our preliminary data suggest that up-regulated synthesis of post synaptic glutamate receptors of the kainic acid-preferring subtype may be such a biomarker. PMID- 1745439 TI - Cerebral and peripheral neurotoxicity of chlorpromazine and ethanol interaction: implications for alcohol and aldehyde dehydrogenase. AB - The effects of certain experimental variables on rodents brain and liver alcohol- (ADH) and aldehyde-dehydrogenase (LALDH) were evaluated. The in vivo and in vitro effect of chlorpromazine on these enzymes was determined. Short-term housing under complete darkness differentially inhibited ADH and ALDH in distinct brain regions with ADH showing more sensitivity than ALDH. The hepatic enzymes studied were not affected by such housing conditions but a non-competitive inhibition of L-ALDH occurred as a consequence of exposure to UV lighting for 3 consecutive weeks. Short-term treatment with chlorpromazine inhibited striatal ADH which was not affected by experimentally-induced hypothermia. Likewise, both hepatic and testicular ADH were noncompetitively inhibited in vitro by chlorpromazine. The results suggest sensitivity of brain and hepatic ADH to environmental housing conditions and indicate a similarity between peripheral and cerebral ADH responses to chlorpromazine. The modulation of ADH and/or ALDH may facilitate the formation of endogenous biogenic amines derived alkaloids which have been implicated in alcohol and extrapyramidal side effects. PMID- 1745440 TI - Neurotoxicity of chlorpromazine and modulation by amantadine as a function of mouse strain. AB - The separate and combined effects of successive administration of amantadine, 100 mg/kg, i.p., and chlorpromazine, 0.2 mg/kg, i.p., on motor activity and whole brain levels of certain biogenic amines and major metabolites were studied in four strains of mice. These were the albino ICR, the inbred BALB/C, C57BL/6 and the hybrid CDF-I mice. Amantadine produced a strain-dependent behavioral stimulation subsequent the fourth dose. This was apparent in ICR and C57BL/6 mouse strains and was followed by a behavioral depression phase occurring during the night in C57BL/6 mice which was antagonized by chlorpromazine. Administration of chlorpromazine alone affected only CDF-1 mouse mobility. Chlorpromazine reduced only ICR mouse brain dopamine without concomitant changes in major acid metabolites. Repeated administration of amantadine prior to chlorpromazine negated this effect. Chlorpromazine enhancement of BALB/C brain serotonin and 5 hydroxyindoleacetic acid was antagonised by pretreatment with amantadine. This antagonism was also evident in BALB/C mouse brain dihydroxyphenylacetic acid. The results suggest genotypic-dependent behavioral and cerebral effects by the drugs studied. The antagonism between amantadine and chlorpromazine on brain amines may explain the therapeutic efficacy of amantadine in modulating chlorpromazine induced extrapyramidal disorders. PMID- 1745441 TI - Enhanced neurotoxicity of 3,3'-iminodipropionitrile following carbon tetrachloride pretreatment in the rat. AB - The consequences of 3,3'-iminodipropionitrile (IDPN) exposure in animals merits attention both because of its unique neurotoxic effects and as a potential model compound of human dyskinetic disorders. An important question that remains to be determined is whether IDPN itself or a putative active metabolite is responsible for the neurotoxic actions of the chemical in vivo. The present work tested the hypothesis that IDPN must be metabolized by the liver to an active metabolite to become neurotoxic. Thus a reduction in IDPN neurotoxicity would be expected when liver function is compromised. Male Long-Evans rats were given ip injections of saline, 100 (IDPN1) or 200 (IDPN2) mg/kg of IDPN for three days. Half of the animals in each IDPN dose group received corn oil po and the other half 1 g/kg of the hepatotoxicant carbon tetrachloride (CCl4) for three days, starting one day before IDPN administration. Body weights were obtained regularly after exposure. Horizontal and vertical motor activity, and acoustic startle response were monitored prior to, and 1,3,9 and 16 weeks after IDPN exposure. An observational rating score was obtained at 1, 3 and 9 weeks. Auditory thresholds for 5- and 40 kHz tones were estimated by reflex modification procedures at 10 weeks. Animals receiving IDPN2 alone displayed the overt behavioral signs characteristic of IDPN intoxication (postural disturbances, head dyskinesias, backward walking, circling, increased motor activity, and decreased startle response). They also showed weight loss, hyperactivity, a transient rearing deficit, decreased startle amplitudes and elevated auditory thresholds for low- and high-frequency tones. None of these symptoms were observed in the animals treated with CCl4 alone, and only a mild transient effect on the observational rating score was shown by the IDPN1 alone animals. In contrast, IDPN1/CCl4 resulted in the same or higher toxicity than the IDPN2 treatment. IDPN2/CCl4 resulted in severe toxicity (38% mortality over a two-week period) and enhanced body weight and behavioral effects compared to IDPN2 alone group. Impairment of xenobiotic biotransformation was confirmed by elevated pentobarbital sleeping time in animals under the same CCl4 dosing regimen. In conclusion, pretreatment with hepatotoxic dosages of CCl4 leads to increased toxicity of IDPN. This suggests that hepatic transformation of the chemical is not required for the manifestation of IDPN-induced neurotoxicity, but instead may be involved in the detoxification of this compound. PMID- 1745442 TI - Modulation of protein kinase C activity by amiodarone and desethylamiodarone. AB - Protein Kinase C (PKC), a Ca(2+)-dependent and phospholipid activated enzyme, regulates a variety of intracellular and extracellular signals across the neuronal membrane. A number of Ca(2+)-dependent enzymes are PKC substrates. PKC activity is modulated by lipophilic compounds including calmodulin inhibitors. Amiodarone, an antiarrhythmic drug is associated with some neurologic and pulmonary side effects and has been shown to interact with calmodulin. The present study describes the effects of amiodarone and desethylamiodarone, a major metabolite of amiodarone, on PKC activity. PKC was partially purified from rat brain on an anion exchange column (DE-52). The interaction of amiodarone and desethylamiodarone with PKC was studied as a measure of altered protein phosphorylation and 3H-phorbol 12, 13-dibutyrate (PDBu) binding. Desethylamiodarone significantly inhibited phosphatidylserine, diacylglycerol and Ca2+ stimulated PKC activity with IC50 of 30 microM. However, amiodarone had no significant effect on PKC activity. Both amiodarone and desethylamiodarone altered the 3H-PDBu binding to PKC and the effect was biphasic. The Scatchard analysis of 3H-PDBu binding to PKC revealed that at lower concentrations (5 microM), amiodarone and desethylamiodarone increased 3H-PDBu binding to PKC with decreased affinity. Whereas, at higher concentrations (greater than 30 microM) these drugs decreased the 3H-PDBu binding. In the presence of Ca2+, phosphatidylserine and PDBu (120 nM) no significant stimulation was observed with low concentrations of amiodarone and desethylamiodarone. However, at high concentrations (50 microM), desethylamiodarone inhibited the PDBu stimulated PKC activity. These data clearly demonstrate that desethylamiodarone a metabolite of amiodarone is a potent inhibitor of PKC activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745443 TI - Evaluation of magnesium, calcium and aluminum metabolism in rats and monkeys maintained on calcium-deficient diets. AB - The epidemiology of amyotrophic lateral sclerosis (ALS) in the Western Pacific indicates that low concentrations of calcium (Ca) and magnesium (Mg) and high levels of aluminum (Al) in soil and water in these foci are etiologically important. To determine the biochemical derangements and metal deposition induced by chronic dietary deficiencies of Ca, we maintained experimental animals on several regimens. Male Wistar rats, weighing 100g, were fed either a standard diet, low Ca diet, low Ca-Mg diet, or low Ca-Mg diet with high Al for 90 days. Ca, Mg and Al content was determined in central nervous system (CNS) tissues and bone using inductively coupled plasma emission spectrometry (ICP). In separate studies, five male Japanese macaques (Macaca fuscata), weighing 3.5 to 5 kg, were fed alternately with diets, normal in Ca, low in Ca, low in Mg, low in Ca-Mg, or low in Ca-Mg with added Al for four-week periods. Serum Ca, Mg, Al, parathyroid hormone (PTH), bone Gla-protein (BGP) and alkaline phosphatase (ALP) were measured after feeding each dietary regimen. Ca and Mg levels in lumbar vertebrae and femur were significantly reduced and bone Al levels were significantly increased in rats fed diets deficient in Ca alone or diets low in Ca-Mg with or without added Al. Al content in bones was also higher in rats fed the Ca deficient diets. In monkeys fed the low Ca-Mg diet with added Al, reduced levels of serum Ca and Mg, serum PTH, BGP, and ALP were apparent. Our data support the conjecture that deranged bone mineralization induced by chronic dietary deficiency of Ca accelerates mobilization of Ca and Mg from bone and deposition in brain. PMID- 1745444 TI - Aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii Peninsula of Japan. AB - Chronic dietary deficiency of calcium (Ca) and magnesium (Mg) with excessive intake of aluminum (Al) and manganese (Mn) has been implicated in the pathogenesis of high incidence amyotrophic lateral sclerosis (ALS) in the Western Pacific. We report two cases of ALS from the Kii Peninsula of Japan with markedly elevated concentrations of Al in central nervous system (CNS) tissues. Six pathologically verified cases of ALS and five neurologically normal controls were studied. Levels of Al, Ca and phosphorus (P) were determined simultaneously by neutron activation analysis (NAA), and Mg concentration was measured by inductively coupled plasma emission spectrometry (ICP) in 26 CNS regions. Al concentrations in the precentral gyrus, internal capsule, crus cerebri and spinal cord were significantly increased in two ALS patients, compared with those of controls. Mean Al concentrations of the 26 CNS regions in these two patients were also higher than those of controls and of the four other ALS cases (p less than 0.01). By contrast, Mg concentrations in the 26 CNS regions were markedly reduced in the ALS cases, compared with controls (p less than 0.01), and the Ca/Mg ratios were significantly increased in the ALS cases (p less than 0.01). Our data indicate that high-incidence ALS in the Western Pacific may result from Ca-Mg dysmetabolism with resultant deposition of Al. PMID- 1745445 TI - Epileptogenic properties of cocaine in humans. AB - Ninety-eight of 945 patients admitted to Hennepin County Medical Center with acute medical complications of cocaine intoxication presented with seizures within 90 min of cocaine ingestion. Cocaine-related seizures were most frequently single, generalized convulsions, and these individuals all had normal cranial CT and EEG. Of the 945 patients, 18.4% of the women presented with seizures, compared with only 6.2% of the men. All subjects who presented with new onset focal seizures following cocaine ingestion had acute cocaine-related cerebral strokes or hemorrhages. Individuals with a history of cocaine-unrelated seizures, had their typical convulsions precipitated with "recreational" doses of cocaine. All four subjects with status epilepticus had ingested massive doses of cocaine, were resistant to medical treatment, and had significant morbidity and mortality. We were able to characterize four subgroups of subjects at risk for cocaine related convulsions. First, individuals who had ingested massive doses of cocaine (2-8 gms) in whom cocaine induced seizures by its direct, dose-related convulsant effects. Second, individuals with a history of epilepsy had their typical seizures precipitated by lowering the seizure threshold. Third, females are at greater risk for cocaine-related compared to males. Fourth, years of chronic, habitual cocaine abuse may result in "chemical" kindling of epilepsy. PMID- 1745446 TI - Challenges facing the medical profession. PMID- 1745447 TI - Recommendations for influenza vaccination: from clinical piety to clinical practice. PMID- 1745448 TI - Breaking the chain of HIV transmission. PMID- 1745449 TI - Achievable influenza immunization rates in the elderly. AB - We sought to determine achievable rates of influenza immunization in a large internal medicine practice in which free vaccination was vigorously promoted. A list of 1,230 patients over 65 years of age constituted the target population. Seven hundred ninety patients (64%) were immunized in the office from September to December 1989. In early 1990, questionnaires were sent to 67 patients who had refused vaccination and to an equal number of age- and sex-matched controls who had either accepted the vaccine or whose immunization status was unknown. Seventy four percent returned the questionnaires. Of the 67 unimmunized patients, 39 (53%) reported that they might be persuaded to accept immunization, whereas 22 (33%) said that nothing could convince them to be immunized. When we added persons who might accept influenza vaccine and persons who had received the vaccine in public clinics to the total number of patients immunized in the office setting, we reached a total of 1,059 patients (86.1% of the total), which we would propose as the maximal achievable immunization rate in this setting. PMID- 1745450 TI - S. Weir Mitchell, Charlotte Perkins Gilman's "The yellow wallpaper," and Capgras' syndrome. PMID- 1745451 TI - Primary care in New York State: report and recommendations of the associated medical schools of New York. AB - Medical education in New York is unique in the country in its scope and its diversity. It is important, as we go forward, that these strengths be neither eroded nor compromised. The AMS member institutions are making a collective commitment to work together to promote changes that will improve medical education for all students by providing them with enriched experience in primary care. Our major resource is faculty. To whatever degree medical schools can influence career choice, it is essential to this aim that the best possible people are placed in the settings in which primary care is taught. The schools will intensify their efforts to recruit and retain such faculty and, in whatever way is appropriate to each institution, provide them with the stature needed to emphasize the value which the school places on primary care. The schools will also work to provide exposure to primary care early in a student's academic career given anecdotal evidence, at least, that such early experience can influence subsequent specialty choice. Finally, the medical schools will assume greater responsibility for graduate medical education. If, with state support, ambulatory teaching sites are developed, the schools will make every effort to assure that they are staffed with high-quality faculty. Residents and students must see primary care practiced with total commitment to quality. It is hoped that, with state-initiated improvements in the practice environment, the ultimate outcome will be an increase in the number of our graduates selecting primary care disciplines for their practices and locating in areas in need of physicians.2+ Corporation, and the Greater New York Hospital Association. We are ready to work with others toward our common objectives, and we call on all of those who share these concerns to participate with us. PMID- 1745452 TI - Epithelioid sarcoma presenting as lymph node metastasis from an unknown primary lesion. PMID- 1745453 TI - Spurious neutropenia: ethylenediaminetetraacetate-dependent in vitro neutrophil agglutination. PMID- 1745454 TI - Sesame seed anaphylaxis. PMID- 1745455 TI - Hospital-specific mortality rates for cardiac surgery. PMID- 1745456 TI - Medical abbreviations and acronyms. PMID- 1745457 TI - Scrotal wall edema presenting as the initial manifestation of nephrotic syndrome. PMID- 1745458 TI - Cancer and health screening in Canterbury general practices. AB - The general practitioners in the Canterbury Area Health Board area were surveyed for their screening policies for cancer and medical conditions. Responses were obtained from 210 (79%), 55% of whom had age/sex registers. Ninety-seven percent provided cervical smears, usually at 1-2 year intervals; 62% offered a female smear taker. Smears were initiated opportunistically by 76%, by age/sex register (47%) or on request by 27%. Breast cancer was screened by 69% using mammography and by 59% using breast physical examination; 73% taught breast self examination. Mammography was recommended every two years for women aged 50-64 years by 45% of responders, and annually to women aged 40-50 years by 19%. Mammography was initiated opportunistically by 88%, on request by 70% and using an age/sex register by 21%. Melanoma was screened by 66%, colorectal cancers in those at high risk by 42%. Testicular self examination was promoted by 43%. Ninety-one percent screened for hypertension, and 51% for hyperlipidaemia, 54% for diabetes mellitus in people without risk factors. Smoking (97%) and alcohol intake (82%) were usually inquired for, and safe sex practices by 59%. Established screening modalities were recommended by most practitioners, but the frequency exceeded current guidelines in many cases; opportunistic screening predominated. PMID- 1745459 TI - Cost analysis of a major burn. AB - A retrospective review was undertaken of 26 patients admitted to Middlemore Hospital between January 1986 to July 1989 with burns totalling more than 30% of total body surface area. An attempt was made to estimate the total cost of successful inpatient management of a major burn using known and assumed values. The new schedule of interboard hospital charges was also employed for greater accuracy. The 20 survivors had a mean initial hospital stay of 68.7 days at a cost of between $37,077 and $40,702 (1989 values) and $46,069 (1991 values). This latter figure equates to an average cost of $647 per patient per day or, alternatively, $927 per % burn. Suggestions to reduce costs and improve treatment include: earlier excision and grafting; the establishment of a regional skin bank and keratinocyte culture facility to aid wound closure; and guidelines on antibiotic prescribing. PMID- 1745460 TI - Simvastatin and side effects. AB - OBJECT: to investigate the symptomatic and biochemical side effect profile of simvastatin (a new cholesterol lowering drug) following routine use in a specialist hospital outpatient clinic. METHODS: all patients (n = 110) newly commenced on simvastatin at the lipid disorders clinic at the Princess Margaret Hospital in the first ten months of prescription availability were asked to complete a side effects questionnaire and biochemical evaluation at six months of therapy. RESULTS: 76.4% of patients reported experiencing no side effects with 8% of patients spontaneously reporting feeling better since commencing therapy. Nineteen point one percent of patients reported experiencing symptoms they attributed to simvastatin but had continued therapy, while a further 4.5% of patients had withdrawn from therapy because of side effects. The most frequently reported side effects were muscle ache (13.6%), and gastrointestinal symptoms (4.5%). No abnormalities in biochemical safety tests occurred. CONCLUSIONS: the rate of side effects reported with prescription use exceeds that previously encountered in clinical trials. Since simvastatin is considered effective and well tolerated it is likely to receive wide acceptance in the management of high risk hypercholesterolaemic patients. However, this study indicates the need for continued physician awareness of the main symptoms and their frequency amongst those treated with simvastatin. PMID- 1745461 TI - Unit dose calendar packaging and elderly patient compliance. AB - A controlled trial of the effect of a unit dose system of tablet/capsule calendar packaging (Webster-Pak) on the rate of successful self medication both in hospital and after discharge to the community has been completed in a geriatric assessment and rehabilitation unit. Eighty-four elderly patients, 45 using calendar packs (study), and 39 using conventional bottles or packs (control), were followed for three months after discharge. There was a significant improvement in patient compliance in the study group over controls on discharge (86.7% vs 66.7%), 10 days (68.8% vs 41.0%), one month (64.4% vs 38.5%) and three months (48.9% vs 23.1%) after discharge. Unit dose packaging is a cost effective method of improving the delivery of medicine in elderly patients, and should be available as part of the health budget. PMID- 1745462 TI - Direct patient telephone access to the coronary care unit: its use and impact on admission delays. AB - Direct telephone access for patients to the Hutt Hospital coronary care unit (CCU) was established in 1989. This paper describes initial experience of 200 consecutive calls and a subsequent study of its impact on admission delays in a further 295 patients. The majority of calls were received between 4 am and noon. Those relating to chest pain made between 4 and 8 am were more likely to be followed by admission than at other times, p less than 0.001. Use of the direct line was associated with quicker admission, 212 (SE 23.2) min compared with 359.2 (23.0), p less than 0.001. For patients with myocardial infarction the difference was even greater, 115 (28.9) (median 90 min) compared with 344.9 (18.9) (median 212 min), p less than 0.001. We conclude that free telephone access to the CCU is a valuable aid to acute coronary care. PMID- 1745463 TI - HIV-1 infection status in two HIV-1 antibody positive infants determined using the polymerase chain reaction. AB - The HIV-1 infection status of two HIV-1 antibody positive infants born to HIV-1 infected mothers was determined using the polymerase chain reaction. HIV-1 genomic sequences were not detected in the white blood cells of either infant suggesting that they were not infected. HIV-1 genomic sequences were detected in the white blood cells of the mothers of both infants and in cells from the one surviving father. These results confirm the value of the PCR detection method for assessing the HIV-1 infection status of infants born to HIV-1 antibody positive mothers. PMID- 1745464 TI - No association between fluoridation of water supplies and sudden infant death syndrome. PMID- 1745465 TI - Pricers thumb. PMID- 1745466 TI - Medical manslaughter. PMID- 1745467 TI - Melanoma patients consume more polyunsaturated fat than people without melanoma. PMID- 1745469 TI - AIDS worldwide. PMID- 1745468 TI - The American Medicare system--disincentive for physicians. PMID- 1745470 TI - Autoimmune diseases in pregnancy: their effect on the fetus and newborn. AB - A variegated group of autoimmune disorders tend to occur in women during childbearing years. Autoantibodies, often of IgG type, directed against the mother's (self) antigens has been well characterized in a number of these disorders. Transplacental transfer of IgG autoantibodies has been frequently demonstrated without demonstrable ill effects of offspring of affected mothers. However, transient neonatal autoimmune syndromes have been described in a subset of infants born with circulating autoantibodies. The time course of clinical symptomatology often parallels the presumed half life IgG immunoglobulins. This review details the clinical manifestations of different transient neonatal autoimmune syndromes and describes possible pathogenic mechanisms. Autoimmune disorders reviewed include connective tissue disorders, thyroid autoimmune disorders, myasthenia gravis, idiopathic thrombocytopenic purpura, and other uncommon disorders. PMID- 1745471 TI - Intraamniotic infection in patients with intact membranes and preterm labor. AB - The purpose of this review was to determine the frequency of intraamniotic infection in women with preterm labor and intact membranes and to assess the need for amniocentesis in these patients. We reviewed reports in the English language literature from the past 10 years in which the frequency of intraamniotic infection was determined by transabdominal amniocentesis. The 16 studies reviewed demonstrated frequencies of positive cultures that varied from 0 to 61 per cent. This extreme variability seems to be the result of diverse patient populations, dissimilar microbiologic techniques, and different definitions of preterm labor. Advanced cervical dilation and poor response to tocolytic agents were two factors associated with a higher frequency of intraamniotic infection. We conclude that each institution must determine the frequency of intraamniotic infection associated with preterm labor in their patient population. In populations with a high frequency of infection, amniocentesis for microbiologic evaluation is recommended for management of preterm labor, especially in patients who have advanced cervical dilatation or who are unresponsive to tocolytic therapy. PMID- 1745472 TI - Are city sun parlor ordinances necessary? PMID- 1745473 TI - The real cause of infant mortality. PMID- 1745474 TI - Another look at the ER. PMID- 1745475 TI - Physician behavior and the family. PMID- 1745476 TI - One way to serve the post-menopausal patient. PMID- 1745477 TI - Teens will listen to this message about AIDS. PMID- 1745478 TI - Ohio physicians speak out on Medicare. PMID- 1745479 TI - Association of epirubicin, etoposide and cisplatin in gastric cancer. A phase II study. AB - Cisplatin-based drug combinations are now currently investigated in an attempt to surpass the results obtainable by 5-FU alone or by 5-FU-containing regimens. We evaluated 29 patients with advanced and measurable gastric adenocarcinoma treated with etoposide, epirubicin and cisplatin. One patient had complete response (3 +/ 7%); 9 patients had partial response (31 +/- 17%); 5 patients (17 +/- 14%) were considered stable (S) and 14 (48 +/- 18%) were classified as progressive. The average survival time for the entire group was 11 months with 25% of the patients alive at 24 months. We feel that cisplatin-containing regimens are promising and deserve further investigations. To clearly explore the potential innovative role of these regimens randomized trials versus FAM or 5-FU alone are mandatory. PMID- 1745480 TI - Acute gastroduodenal mucosal injury after cisplatin plus etoposide chemotherapy. Clinical and endoscopic study. AB - The effects on gastric and duodenal mucosa induced by cisplatin plus etoposide (PE) chemotherapy were investigated in 32 patients with lung cancer. They were submitted to gastroduodenoscopy before receiving cisplatin 100 mg/m2 (day 1) plus etoposide at a mean dose of 107 mg/m2 (days 1, 3 and 5). Endoscopic examination was repeated on day 8. Before chemotherapy, 22 patients showed normal endoscopic appearance and 10 minimal lesions (3 or fewer erosions). After chemotherapy, 16 remained normal, 1 had minimal lesions and 15 developed major lesions: 11 gastric or duodenal multiple erosions, 1 diffuse erosive gastritis, 2 gastric and 1 duodenal ulcer (p less than 0.001). No difference was observed in the number of vomiting episodes nor in severity of upper gastrointestinal symptoms between the patients who remained normal and those who developed mucosal injury. We conclude that PE chemotherapy can have a properly called gastroduodenal toxicity, leaving nausea and vomiting out which are rather due to central than peripheral mechanisms. Some trials are necessary to investigate which kind of drugs (H2 receptor blockers, sucralfate, prostaglandin E analogues) may be useful in preventing acute gastroduodenal mucosal injury induced by PE chemotherapy. PMID- 1745481 TI - Combined chemotherapy and radiotherapy for lymphomas of Waldeyer's ring. AB - The management of 47 patients with stage I and II Waldeyer's ring lymphomas was reviewed. Twenty-one of them received radiotherapy only, and the other 26 received combined chemotherapy and radiotherapy. Patients with primary disease in the nasopharynx, high-grade histology or advanced age were associated with poorer survival. Although the complete response rates were similar, the patients receiving combined chemotherapy and radiotherapy had significantly fewer relapses and a better disease-free survival. However, their survivals were similar. The lack of improvement in the overall survival might be due to the effectiveness of salvage chemotherapy in treating some of the radiotherapy failures and the occasional chemotherapy-related mortality. PMID- 1745482 TI - Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma. AB - A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM. PMID- 1745483 TI - Intermediate dose of intravenous melphalan in advanced multiple myeloma. AB - Eighteen patients with advanced multiple myeloma resistant to VAD chemotherapy (vincristine, Adriamycin, dexamethasone) were treated with intravenous melphalan in a single-pulse dose of 50-70 mg/m2. Objective response (greater than or equal to 50% reduction of the monoclonal protein) was observed in 9 patients. The median duration of remission in the responding patients was 6 months and the median survival 11.5 months. The main toxicity noted was bone marrow suppression. We conclude that intermediate doses of intravenous melphalan are a useful therapeutic modality in refractory or relapsing myeloma patients. PMID- 1745484 TI - Influence of serum derived from patients with head and neck cancer on natural killer cell activity. AB - The influence of serum from 23 patients with head and neck cancer on natural killer (NK) cell activity was analyzed using a double-layer agar assay, in which NK cells show an activity to inhibit the colony growth of K562 cells. In contrast to normal serum (or no treatment), serum from cancer patients reduced the inhibitory activity of NK cells, not only of autologous NK cells but also of allogeneic NK cells. These results suggest that the serum of patients with head and neck cancer may have some inhibitory factors on NK cell activity and may be involved in host resistance to tumor growth in vivo. PMID- 1745485 TI - Diagnosis of anal carcinoma--doctor's finger still the best? AB - Symptoms, delay in diagnosis, tumour stage and the clinical value of a follow-up programme were studied in 107 patients admitted to the Norwegian Radium Hospital for anal canal carcinoma. Sixty percent of the patients had advanced tumours (T3 or T4) at the time of diagnosis, while 1/4 presented with metastases to the pelvic lymph nodes and 5% with distant metastases. The most frequent initial symptoms were anal bleeding and pain (38 and 23%, respectively). About 3/4 of the patients experienced more than 1 month's delay of diagnosis, either because of the patient himself (1/2 of the cases), doctor (1/5 of the cases) or hospital (1/10 of the cases). About 1/3 of the patients had more than 6 months' total delay. The follow-up after treatment (chemoradiotherapy) shows that frequent digital rectal examination is the most important procedure. Some patients may benefit from serum carcino-embryonic antigen measurement, liver ultrasonography or chest X-ray. PMID- 1745486 TI - Hyperimmunoglobulinemia D following cancer chemotherapy. AB - Five classes of serum immunoglobulin levels were investigated in 107 children with malignant or benign tumors. Hyperimmunoglobulinemia D (hyper-IgD) was observed in 31 of 82 children who were in complete remission off chemotherapy with a median follow-up of 4.5 years after cessation of chemotherapy. On the other hand, hyper-IgD was not found among 12 children with malignant or benign tumors treated with chemotherapy and a low incidence of hyper-IgD was observed during chemotherapy (1 of 13 cases). The result indicates that hyper-IgD is not uncommon in children off chemotherapy, suggesting that dysregulation of IgD synthesis persists long after cessation of antineoplastic drugs. PMID- 1745487 TI - Acute and delayed emesis after cisplatin-based regimen: description and prevention. AB - Lorazepam, dexamethasone and high-dose metoclopramide were given to 54 patients to prevent emesis induced by cisplatin (50-120 mg/m2) on day 1, while prochlorperazine and dexamethasone were administered on days 2 and 3 for control of delayed emesis. Nausea and emesis were recorded from day 1 to day 8. This combination was well tolerated. Prevention on day 1 was complete for 72% of patients and satisfactory (less than or equal to 2 emeses on day 1) in 85%. From days 2 to 8, no emesis, less than or equal to 2 and greater than 2 episodes occurred in 70, 11 and 19%, respectively. Overall control (days 1-8) was complete in 55.5% and satisfactory (less than or equal to 2 emeses on day 1 and/or less than or equal to 2 emeses from days 2 to 8) in 74%. Delayed emesis started on days 2-5. Mean duration was 2.6 days. Delayed nausea or emesis were more frequent when emesis occurred on day 1. Based on data previously reported and on these observations, better ways to prevent delayed events are discussed. Further trials must record systematically delayed side effects. PMID- 1745488 TI - Randomized trial for the control of acute vomiting in cisplatin-treated patients: high-dose metoclopramide with dexamethasone and lorazepam as adjuncts versus high dose alizapride plus dexamethasone and lorazepam. Study of the incidence of delayed emesis. AB - This study investigated the antiemetic activity of two different acute antiemesis regimens in patients receiving cisplatin-based chemotherapy. Seventy-four patients were treated with high-dose metoclopramide, dexamethasone and lorazepam (MDL) and 71 patients received high-dose alizapride, dexamethasone and lorazepam (ADL). Complete protection from vomiting was 50% in MDL-treated patients as compared with 30% in the ADL arm (p = 0.04). Incidence of delayed emesis was assessed in the first 82 patients accrued for the 120 h postcisplatin, being 69 and 60% in MDL and ADL, respectively. PMID- 1745489 TI - Dairy products and the risk of prostatic cancer. AB - Dietary indicators of prostatic cancer risk were analyzed in a case-control study conducted in Northern Italy on 96 histologically confirmed cases and 292 controls in hospital for acute, nonneoplastic or genital tract diseases. There was a significant trend in risk as regards frequency of milk consumption: compared with nondrinkers or occasional milk drinkers, the relative risk (RR) was 1.2 (95% confidence interval, Cl, 0.7-1.9) for 1 or 2 glasses per day and 5.0 (95% Cl 1.5 16.6) for 2 or more glasses per day. By contrast, no consistent association was observed with measures of cheese or butter intake. This might, at least in part, be attributable to the lower measurement errors for milk (which tends to be consumed in regular and uniform patterns) as compared with other dairy products. However, the interpretation of these findings is not clear, since other sources of animal fat, like eggs or meat, as well as a summary fat score, were unrelated to prostatic cancer. Although these limitations and uncertainties are substantial, this study provides further evidence that elevated milk consumption may be an indicator of prostatic cancer risk. PMID- 1745490 TI - Results of a nationwide study on the three-field lymph node dissection of esophageal cancer. AB - In order to determine the operative indications of three-field lymph node dissection of esophageal cancer, attempts were made to collect data concerning procedures performed between 1983 and 1989 in major institutions in Japan, and the results from institutions performing three-field or two-field lymph node dissection were compared. The treatment results of three-field lymph node dissection were better than those after two-field dissection, except for early or advanced cancer. The survival rate improved by the three-field as compared with the two-field lymph node dissection; however, since surgery was invasive, some complications such as recurrent nerve paralysis were frequent. The results show that the indication of three-field lymph node dissection has to be carefully determined for each patient. PMID- 1745491 TI - Immunohistochemical detection of estrogen receptors in paraffin sections of human thyroid tissues. AB - The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells. PMID- 1745492 TI - Pregnancy-induced cytotoxicity of splenocytes against mammary tumor cells in rats. AB - Our earlier observations indicate the possibility of involvement of a 'host factor' in pregnancy-induced protection against mammary carcinogenesis. The present investigation is an attempt to determine if this "host factor" is of immunological nature. Rat mammary tumors induced by 7,12 dimethylbenz[a]anthracene were used as target, and splenocytes from parous rats of the same strain were used as effector cells. The parous rats were divided into two groups according to the time period after parturition. Group 1 contained rats which were 5-13 days after delivery, group 2 had rats 14 or more days after parturition. In vitro cytotoxicity was determined by incubating the tumor cells with spleen cells in the target:effector ratios of 1:3, 1:10 and 1:30. Both groups 1 and 2 showed significant lysis of mammary tumor cells. These results were confirmed by the trypan blue exclusion test. The results showed a significantly higher cytotoxic capability of the spleen cells from parous rats against mammary tumor cells as compared to spleen cells from age-matched nulliparous rats. PMID- 1745493 TI - Differentiated practice: today, tomorrow and the future. PMID- 1745494 TI - Esthesiometry as an indicator of corneal health. AB - We review the literature regarding changes in the structure and function of the cornea as an index of the physiological status of the tissue. Accurate measurement of corneal sensitivity may be the most reliable test of long-term corneal compromise inasmuch as the edema response, the most popular test of corneal physiological integrity, shows "adaptation". Although reduced sensitivity has been associated with corneal hypoxia, decreased corneal pH may also play a major role. Certainly, small departures of pH from normal levels in the body can lead to major depression of neural function. Traditionally, mechanical sensitivity of the cornea has been measured with procedures based on the von Frey hair. More recently, esthesiometry has been performed with the use of a puff of air, a chemical stimulant, and heat. Results from early trials with these procedures are encouraging in terms of the development of a viable clinical method for assessing metabolic effects on the cornea from contact lens wear. PMID- 1745495 TI - The significance of the microcyst response: a review. AB - Epithelial microcysts have been identified as a significant corneal response to contact lens wear. The characteristics of the microcyst response are outlined and factors which influence the level of microcysts including lens type, oxygen transmissibility (Dk/L), and wear schedule are discussed. Understanding of the morphology, pathology, etiology, and clinical significance of microcysts is currently incomplete and various hypotheses are discussed. PMID- 1745496 TI - Posterior corneal surface toricity and total corneal astigmatism. AB - The influence of posterior corneal surface toricity upon total corneal astigmatism was investigated in 60 young subjects (mean age 22.04 +/- 3.24 years). Both surfaces were found to be flatter horizontally than vertically. Astigmatism arising from the anterior corneal surface was therefore reduced by astigmatism of the opposite sign arising from the posterior surface. Had the toricity of the posterior corneal surface been purely governed by that of the anterior surface this reduction would have amounted to about 5%. However, the posterior surface was found to exhibit additional toricity bringing about a greater reduction of total corneal astigmatism amounting to approximately 14%. PMID- 1745497 TI - Retinal eccentricity of fusion detail affects vergence adaptation. AB - Adaptation of tonic vergence ("vergence adaptation" or "prism adaptation") may be produced by sustained accommodative, disparity, or proximal vergence innervation. Phoria measures were used in the present study as indices of tonic vergence adaptation to convergence and divergence stimuli in five subjects. Amblyoscope targets stimulated fusion either over the central or peripheral retina while holding accommodative and proximal stimuli constant. The magnitude and rate of tonic vergence adaptation were greater under the central fusion condition than under the peripheral fusion condition, even though the vergence stimuli were matched between central and peripheral fusion conditions. These results show that tonic vergence adaptation is influenced by the retinal eccentricity of target fusional patterns. However, additional work is required to identify the mechanism(s) underlying this eccentricity effect. PMID- 1745498 TI - Efficacy of chlorine disinfection of soft contact lenses. AB - We evaluated the chlorine system SOFTAB (Alcon) for the disinfection of soft contact lenses. The results indicate that a 1000-fold reduction in microorganisms was achieved within 6 h. Even with the slight interference of residual cleaner and the more significant interference of organic matter disinfection was still achieved. PMID- 1745499 TI - Chemical inactivation of microorganisms on rigid gas permeable contact lenses. AB - The efficiency of four contact lens disinfectant formulations was tested against three types of bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, and Serratia marcescens) and one fungus (Aspergillus niger). The bacteria were tested both as free suspensions and after attachment on surfaces of rigid gas permeable contact lenses (RGPCL). The disinfection data were used to calculate the death rates and decimal reduction times for the test organisms. P. aeruginosa was the most sensitive and A. niger was the most resistant organism to the disinfectants. Scanning electron micrographs showed that P. aeruginosa occurred mostly as single cells, with little extracellular material, on the lens surface. In contrast, S. marcescens produced copious amounts of capsular material layered on the lens surface, promoting cell aggregation. Transmission electron micrographs revealed that bacterial cells were physically separated from the lens surface by a space barricaded with capsular material. PMID- 1745500 TI - Vistech VCTS 6500 charts--within- and between-session reliability. AB - The aim of the study was to measure the reliability of the Vistech VCTS 6500 charts, in test score units, in order to allow clinicians to derive estimates of what constitutes a clinically meaningful change in performance over time. The reliability of a more familiar test, Bailey-Lovie high contrast visual acuity, was also measured to provide a comparison. Patients with normal vision and with early or subtle eye disease were recruited so that the results would be representative of the population likely to present for primary vision screening. Patients were tested on all three VCTS charts on two separate occasions at least 3 weeks apart to give estimates of within- and between-session reliability. Reliability was found to be low in all circumstances; between-session reliability could be improved by using the mean score for the three charts, but the 95% range of difference scores still encompassed at least one-half of the total performance range of the test. It was concluded that Vistech charts are unlikely to be of use for clinical measurements or for research studies. PMID- 1745501 TI - An ophthalmic survey of African patients presenting at rural eye clinics in South Africa. AB - The records of 10,254 people attending rural eye clinics in South Africa during 1984-85 were analyzed to determine the reasons for presentation. The main reasons for presentation were refractive error, conjunctivitis, and cataract. It is expected that population growth plus the increased vocational needs for the correction of refractive errors will result in an increased demand for optometric services in rural eye clinics. It is suggested that optometry has a major role to play in providing primary eye care services to the underserved populations of the South African homelands. PMID- 1745502 TI - Bilateral monocular diplopia secondary to occult diabetes mellitus. AB - A 68-year-old man presented with transient, bilateral, vertical, monocular diplopia as an initial manifestation of diabetes mellitus. The diplopia was determined to be of lenticular origin, but was not found to be secondary to the usual refractive changes. Rather, it is presumed to be due to prismatic alterations caused by index of refraction differences within the crystalline lenses. It is not known what other factors relate to the development of this type of diplopia in the diabetic patient. PMID- 1745503 TI - Congenital retinal macrovessel. AB - Congenital retinal macrovessel is a rare condition in which anomalous retinal vessels cross the macula. Visual impairment can result if the anomalous vessels pass across the foveola, if foveolar cysts form, or if hemorrhage occurs. A now 17-year-old African-American female has an anomalous retinal vein that crossed the macular region beyond the horizontal raphe in her left eye. This patient exhibited the classic characteristics of congenital macrovessels. Her visual acuity remained unaffected after a 5-year follow-up and therefore treatment was not required. PMID- 1745504 TI - Tinted lenses and the ANSI standards for traffic signal transmittances. AB - The transmittance properties of 96 tinted lenses were examined to determine whether these lenses met the American National Standards Institute (ANSI) Z80.3 standards for traffic signal transmittances and color shifts. Transmission functions of the lenses were measured using a Zeiss Spectrophotometer, and the luminous transmittances and color shifts were calculated according to the ANSI guidelines. Approximately 50% of the sampled tinted lenses failed to meet at least 1 of the ANSI requirements. Lenses that failed to meet several ANSI requirements were often special purpose sun lenses. Although the special purpose tinted lenses do not have transmittance requirements for traffic signals, it is not always clear from the manufacturers' brochures that the lenses may be unsuitable for driving. PMID- 1745505 TI - Root agenesis in developing canines as a complication of intranasal antrostomy. AB - A case is reported in which the roots of both maxillary canines failed to develop, a defect that could be traced to antral surgery when the patient was 8 years of age. The differential diagnosis of such a finding is proffered. The maxillary antrum is described, and aspects of the surgical procedure, the nasal antrostomy, used in this patient are discussed. A brief outline of current thought on the mechanisms of eruption of teeth is appropriate, and treatment of the symptomatic tooth is mentioned. PMID- 1745506 TI - Temporomandibular joint dysfunction syndrome: a close association with systemic joint laxity (the hypermobile joint syndrome) AB - Sixty-two patients admitted for elective reconstructive surgery of the temporomandibular joint (TMJ) and eight seen as outpatients with a chief complaint of TMJ dysfunction during the same time interval were evaluated for possible etiologic factors contributing to the disease. All hospitalized patients had severe, end-stage degenerative changes within the TMJ, whereas outpatients had less severe disease and did not require surgery. TMJ dysfunction in some patients was said to be a result of established causes including bruxism, malocclusion, and trauma. No patient in this series had evidence of a systemic inflammatory polyarthritis. Of the 70 patients, 38 (54%) met criteria, based on those of Carter and Wilkinson, as modified by Beighton et al., sufficient to warrant a diagnosis of the hypermobile joint syndrome. Five patients had classic Ehlers-Danlos syndrome and therefore were not patients with "benign hypermobility," and an additional two cases were described as "marfanoid" and as possible Ehlers-Danlos syndrome, respectively. Radiographs showed TMJ hyperextensibility in four hypermobile patients. Long-term surgical outcome was identical in the hypermobile and nonhypermobile groups. The incidence of hypermobility in this series is strikingly higher than the expected incidence in an otherwise population. Magnetic resonance images of the TMJs on separate groups of asymptomatic normal and hypermobile women identified excessive anterior movement in the hypermobile group, together with abnormal anterior disk position in some. We hypothesize that hypermobility within the TMJ may cause accelerated disk destruction and degenerative disease. PMID- 1745507 TI - Effect of fascia repair of the temporomandibular joint disk of sheep. AB - The effects of temporal fascia graft repair of temporomandibular joint disk perforation on intra-articular structure were examined on four sheep. Four sheep had bilateral disk perforations. At 20 weeks the perforation in the right joint was repaired with a temporal fascia graft. At 40 weeks the sheep were killed and the joints were examined radiologically and histologically. It was found that the temporal fascia graft did not survive and the disks remained perforated. However, histologically and radiologically there were fewer changes than in the joints where the perforated disks were not repaired. PMID- 1745508 TI - Evaluation of 0.12% chlorhexidine rinse on the prevention of alveolar osteitis. AB - A double-blind study evaluated the ability of 0.12% chlorhexidine rinse to decrease the incidence of localized alveolar osteitis after the removal of mandibular third molar teeth. One hundred sixty extraction sites in 80 patients were evaluated. A statistically significant decrease in the incidence of dry socket was seen in patients using the chlorhexidine rinse with no significant adverse reactions. Thus a 0.12% chlorhexidine rinse is shown to be an effective means of decreasing alveolar osteitis that may follow removal of third molar teeth. PMID- 1745509 TI - Validity of a risk-related patient-administered medical questionnaire for dental patients. AB - In this study the validity of a patient-administered risk-related medical questionnaire for dental patients was tested. The answers given on the questionnaire were compared with the results of a verbal history taken by a physician. This verbal history was considered the "gold standard." The sensitivity and specificity of the medical questionnaire appeared to be sufficiently high, and the kappa values of the separate questions were satisfactory. The questionnaire was found to be valid in the registration of medical problems in dental patients, but combination of the two methods is recommended. PMID- 1745510 TI - Ewing's sarcoma of the temporal bone. A case report. AB - An 11-year-old girl with a primary Ewing's sarcoma in the squamous temporal bone is described, and differential diagnosis and management are discussed. The membranous bones of the skull are rare sites for a primary Ewing's sarcoma; the squamous temporal bone has not been previously described as a primary site. PMID- 1745511 TI - Viruses and chronic disorders involving the human oral mucosa. AB - Viruses have been implicated in the etiology of several chronic disorders of the oral mucosa. Most of these associations have been with DNA viruses, particularly certain herpesviruses, which are associated, for example, with some cases of erythema multiforme and with hairy leukoplakia. Papillomaviruses are associated with various papillomatous lesions, focal epithelial hyperplasia, and possibly with some carcinomas. Viruses may possibly be associated with recurrent aphthae, Behcet's syndrome, and some dermatoses. The literature concerning these possible associations is reviewed. However, much more research needs to be done before the full story of viral associations with oral mucosal disorders can be written. PMID- 1745512 TI - Effects of pilocarpine on salivary flow in patients with Sjogren's syndrome. AB - Pilocarpine, a muscarinic-cholinergic agonist drug, has been reported to stimulate salivary flow in patients with salivary gland dysfunction. Previous studies involved heterogeneous groups of patients with salivary gland dysfunction and examined the short-term, single-dose, tablet form of pilocarpine. In this single-blind, placebo-controlled study we examined the long-term effects of pilocarpine administration on patients with definitively diagnosed Sjogren's syndrome (SS). Nine subjects with SS who received pilocarpine, and nine age- and sex-matched SS control subjects who received a placebo, participated. Baseline predosing sialometric and clinical data were obtained for all subjects. The study group used 2% pilocarpine as a liquid ophthalmic drop preparation, four drops three times per day, for 6-weeks. Identically appearing placebo solution with the same dosing schedule and duration was used for the control subjects. Sialometric and clinical examinations were performed. The results indicated a significant overall increase in both whole unstimulated salivary flow (0.15 +/- 0.03 ml/min in study subjects vs 0.02 +/- 0.001 ml/min in control subjects; p less than 0.001) and parotid stimulated salivary flow (0.14 +/- 0.04 ml/min in study subjects vs 0.009 +/- 0.002 ml/min in control subjects; p less than 0.001) in the pilocarpine group as compared with the placebo group. The results of this study support the use of pilocarpine to increase salivary flow in patients with SS. PMID- 1745513 TI - Are there psychologic predictors of treatment outcome in temporomandibular joint pain and dysfunction? AB - This study explores the relationship between diverse psychologic factors and treatment outcome in temporomandibular joint pain and dysfunction (TMJPD). During assessment, 178 patients with TMJPD were given a pressure pain threshold and tolerance task and completed the Basic Personality Inventory, the Illness Behavior Questionnaire, the Multidimensional Health Locus of Control, the Perceived Stress Scale, and the Ways of Coping Checklist. Subjects also answered questions pertaining to TMJPD symptomatology, including chronicity and severity. After conservative treatment with simple jaw exercises and ultrasound, patients were contacted again at 5 months to complete a follow-up questionnaire package similar to the initial questionnaire battery. Percent reduction in average pain intensity and perceived TMJPD severity were used as outcome criteria. The data were analyzed with discriminant function analyses. One hundred patients responded to the follow-up questionnaire. Patients who reported more than a 50% reduction in average pain intensity tended to be less inclined to accept responsibility for their problems and were slightly better able to distance themselves from their problems than the less improved groups. Those who reported more than a 50% reduction in TMJPD severity indicated that the condition was not associated with an identifiable onset event and that the condition had become moderately worse between onset and first seeking help. PMID- 1745514 TI - Recurrent aphthous ulceration with zinc deficiency and cellular immune deficiency. AB - Zinc deficiency (serum zinc level 65 micrograms/dl) and cellular immune deficiency (confirmed by lymphoblastic transformation assay) were found in a 15 year-old boy who had had recurrent aphthous ulceration for 6 years. Despite the previous therapy (orally administered steroid, isoprinosine, interferon, lysozyme, and local treatment), the ulcers recurred monthly. After 3 months of zinc therapy (50 mg zinc sulfate orally three times daily) the aphthae disappeared and did not reappear for 1 year. The lymphoblastic transformation activity and serum zinc levels were also normalized with this treatment. PMID- 1745515 TI - Occurrence of oral mucosal necrosis in a patient with barbiturate-induced coma. AB - Although dermal lesions in patients with drug poisoning have been widely documented, similar oral conditions are seldom reported. A case of cutaneous and oral mucosal necrosis related to barbiturate-induced coma is reported. PMID- 1745516 TI - Oral Crohn's disease with late intestinal manifestations. AB - Oral Crohn's disease has been reported frequently in the last two decades with and without intestinal manifestations. In the latter case it is considered one of the orofacial granulomatoses. This reference is claimed to eliminate the patient's distress caused by the term Crohn's disease. There has been much doubt whether intestinal Crohn's disease will eventually develop in these patients. A case is reported in a 10-year-old West Indian girl in whom oral Crohn's disease developed at the age of 10 years and was followed by rectal Crohn's disease 9 years later. In this article the term Crohn's disease is used to describe those patients with intestinal manifestations with or without oral disease whereas oral Crohn's disease is used for those who have only oral manifestations. PMID- 1745517 TI - Choristomas of the oral cavity: a review. AB - The choristoma is a tumorlike mass of normal cells in an abnormal location. Intraoral choristomas have been reported under a wide variety of names. This comprehensive review of the English-language literature on oral choristomas offers a classification of these lesions, analyzes their clinical and histologic features, and discusses possible pathogeneses and treatment. PMID- 1745518 TI - Characterization of the enamel ultrastructure and mineral content in hypoplastic amelogenesis imperfecta. AB - Amelogenesis imperfecta (AI) comprises a diverse group of hereditary enamel disorders that are characterized by hypoplastic and in some cases hypomineralized defects. The specific biochemical abnormalities remain unknown for all AI types, making histologic and chemical analyses of affected dentitions essential for resolving the etiology of AI. The purpose of this investigation was to characterize the ultrastructure and mineral content of smooth hypoplastic AI enamel. The AI enamel showed no evidence of surface pitting and was uniformly reduced in thickness by approximately 60% compared with control enamel. Imbibition studies indicated that the AI enamel was generally porous. The first 30 microns of AI enamel adjacent to the dentinoenamel junction was translucent with poorly formed prisms. Abnormal prism structure was seen throughout the AI enamel. Amorphous, presumably organic material that may have been retained enamel protein was also seen. Although the crystallite widths were similar in both AI and normal enamel, the AI teeth showed areas where the crystallite order and continuity appeared disrupted. The mean mineral content was similar for all variables measured except sodium, which was significantly lower in the AI teeth. The calcium concentration was very low in the AI enamel directly adjacent to the dentinoenamel junction and showed a steeper concentration gradient moving from the dentin to the surface compared with control teeth. It may be concluded that the ameloblasts in smooth hypoplastic AI produce a tissue of reduced thickness, which is excessively porous and displays alterations in its ultrastructural organization. PMID- 1745519 TI - In vitro determination and quantification of 30% hydrogen peroxide penetration through dentin and cementum during bleaching. AB - Bleaching pulpless teeth with 30% hydrogen peroxide was reported to cause external cervical root resorption. It was hypothesized that H2O2 penetrated open dentin tubules to initiate an inflammatory response that could result in root resorption. No direct experimental evidence was provided to support this theory. An in vitro model for determination and quantification of H2O2 penetration during bleaching procedures is suggested. Artificial defects of the cementum covering the cementoenamel junction were performed in 22 extracted human premolars. After 15 minutes of thermocatalytic bleaching, H2O2 could be detected in the medium surrounding all the tested teeth. Cervical root permeability to 30% H2O2 could reach up to 82% of the total amount applied. PMID- 1745520 TI - External root resorption after bleaching: a case report. AB - An external root resorption occurred after bleaching and was diagnosed radiographically in a 26-year-old female dental assistant. The resorption was noticed 6 months after bleaching. The involved tooth had no history of trauma. An attempt to stop the resorption by using calcium hydroxide failed. The perforation was corrected surgically with amalgam. PMID- 1745521 TI - Localization of anatomic structures before endodontic surgery with tomograms. Report of a case. AB - Tomograms taken before endodontic surgery can demonstrate the location of root apices relative to adjacent anatomic structures. This buccolingual perspective is not depicted on conventional periapical or panoramic radiographs. Accurate length determination from the root apex to the inferior alveolar canal is simplified, and the relationship of root surfaces to the buccal and lingual plates is well visualized on the tomographic images. PMID- 1745522 TI - Digitally subtracted linear tomograms: three techniques for measuring condylar displacement. AB - Using digital subtraction enhancement, we compared the accuracy of three tomographic technique variations for quantifying small changes of condylar position. A phantom made of skeletal material and an adjustable mechanical stage provided 0.1 mm positioning accuracy of the condylar segment. Linear tomographic images were made with the condyle in a centered position and at each of three 1 mm increments of displacement in two of three directions (inferior, and posterior or lateral). Variations for frontal views included arbitrary (+20 degrees) and individualized (+10 degrees) horizontal correction of the condylar axis. Variations for lateral views included the arbitrary and individualized correction and a fully corrected vertical (+5 degrees) and horizontal (+10 degrees) adjustment. Blinded observers made repeated measurements on randomized subtraction images with a digitizing tablet. Film images were subtracted twice, and each subtraction was read twice by two examiners. The study was repeated with a second series of films treated in an identical manner. Mean values for measurements, standard deviations, and absolute values of differences between measured and expected values were calculated for each subtraction. Analysis of variance identified statistically significant sources of variation in repositioning the phantom and producing exact displacements of the condyle. Average absolute value of differences from expected values were similar for the three techniques and for frontal and lateral orientations and increments of displacement. Typical absolute value of difference for any technique was 0.2 mm for posterior, 0.2 mm for lateral, and 0.1 mm for inferior displacements. Significantly greater accuracy of inferior displacement measures was attributed to greater accuracy of registration of the fossa in its cranio-caudal dimension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745523 TI - Radiographic detection of occlusal caries in noncavitated teeth. A comparison of conventional film radiographs, digitized film radiographs, and RadioVisioGraphy. AB - The aim of this study was to compare the accuracy of conventional film radiographs, digitized radiographs, and RadioVisioGraphy (RVG) for the detection of dentinal caries in occlusal surfaces of noncavitated extracted teeth. Eighty one fully erupted extracted third molars were assessed by four observers using five radiographic methods: conventional film radiographs, digitized radiographs with contrast enhancement and with a filtering procedure, and RVG with contrast enhancement and with x function. Scoring criteria were dichotomous. Histologic sections (500 to 600 microns thick) served as the validation criterion. The two digital methods with contrast enhancement tended to perform more accurately than, although not significantly different from, the other three methods (p greater than 0.05). Average likelihood ratios (true positive/false positive) were 4.3 (conventional film radiographs), 4.4 (RVG with contrast enhancement), 3.6 (RVG with x function), 4.9 (digitized radiographs with contrast enhancement), and 3.7 (digitized radiographs with filtering procedure). Observers 1 and 2 (oral radiologists) performed better than observers 3 and 4 with all five methods (p less than 0.005). PMID- 1745524 TI - Evaluation of the new RadioVisioGraphy system image quality. AB - A comparison of the physical properties of a new charge-coupled device-based direct digital intraoral radiographic system, its predecessor, and high-speed silver halide intraoral radiographic films is reported. The new system proved to have a higher dose dynamic than the former device. The resolving power of the new system is 11 line pairs/mm compared with a maximum of 14 line pairs/mm for intraoral film. PMID- 1745525 TI - Regrowth of mandibular coronoid processes. PMID- 1745526 TI - Postpermanent dentition. PMID- 1745527 TI - Maxillary canine: present or not? PMID- 1745528 TI - Monoclonal antibodies for septic shock: in or out of the barn door? PMID- 1745529 TI - External review in the brave new world of continuous quality improvement. PMID- 1745530 TI - Can an external quality review system avoid the inspection model? PMID- 1745531 TI - Medicare: a strategy for quality assurance, IV: Medicare conditions of participation and quality assurance. AB - This article, the fourth of a series, summarizes the conclusions of the review of the Medicare conditions of participation and accreditation conducted by the Institute of Medicine (IOM). Difficulties in measuring outcomes of care, limitations in survey information, attitudes toward sanctions, and variation in survey procedures are discussed. PMID- 1745532 TI - Expanding on the role of patient as consumer. PMID- 1745533 TI - The merging of quality paradigms--meeting patient needs while staying true to science. PMID- 1745534 TI - Quality improvement in health care: is the patient still left out? AB - Quality improvement methodologies as applied to health care reflect a traditional practitioner-centered approach to defining and improving quality of services. However, health care must reconcile the values, needs, and preferences of providers with those of consumers if effective quality improvement programs are to be developed. PMID- 1745535 TI - The second generation of quality review? PMID- 1745536 TI - Developing, assessing, and refining quality of care criteria for a CHAMPUS mental health services demonstration. AB - CHAMPUS established a contracted provider arrangement demonstration in the Norfolk, Virginia area. This article describes the development, assessment, and refinement of the quality monitoring criteria used to assess quality of care. Of 3,303 cases reviewed, 66% failed one or more criteria in two levels of review by nonphysician reviewers and were referred to peer reviewers. The referral problem was confirmed by the peer reviewer in at least 57% of the 2,177 cases. The criteria should undergo complete specificity and sensitivity testing, be expanded to include more outcome measures, and be applied to other geographic areas before use by other third party payors. PMID- 1745537 TI - [Introduction to the theme. Current knowledge in shoulder surgery--II]. PMID- 1745538 TI - [Assessment of shoulder function]. AB - In 1980, a major study began on the recovery of shoulder function following injuries of various kinds. In order to try and assess shoulder function and it's recovery following injury, it became apparent that diagnostic assessments of the shoulder were of little value, and the Author worked on designing a method of shoulder functional assessment what would allow easy and repeated assessment of shoulder function at various intervals following injury. This method of shoulder functional assessment is now used as a standard practice in many centres, throughout the world, and this paper aims to present the clinical method of functional assessment, as used by the Author, in plotting progress following injury over a number of years. The method has been extensively used by the author and others over the past ten years, in studying the recovery of shoulder function in different disease processes, after injuries and after various treatments, including surgery. PMID- 1745539 TI - [Examination of the non-injured shoulder]. AB - Modern imaging methods are undeniably very attractive. They should make possible an easy study of the musculotendinous rotator cuff of the shoulder joint, lesions of which are the cause of most painful or stiff shoulder syndromes. However, not all shoulder symptoms are due to rotator cuff lesions. Also, not all methods of imaging are equally suited to showing the different cuff lesions. Further, one cannot consider the treatment of a symptomatic shoulder without having an assessment of the present condition upon which to gauge the functional improvement due to the treatment. Hence clinical examination of the painful shoulder remains essential. This makes it possible (1) to exclude an extra articular pathology, (2) to choose the method of imaging most suited to showing the suspected lesion, and finally (3) to quantify the functional state of the shoulder. PMID- 1745540 TI - [Relationship of acromial architecture and diseases of the rotator cuff]. AB - Variations in the architecture of the coraco-acromial arch can lead to a clinically symptomatic rotator cuff lesion. Differences in the shape and slope of the acromion, anterior acromial spurs and inferior protruding acromio-clavicular osteophytes decrease the volume of the subacromial space, leading to impingement. Recent anatomic, radiographic, biomechanic and stereophotogrammetric studies have confirmed these architectural variations and their effect on the contents of the subacromial space. Abnormal contact between the acromion and these soft tissues can result in pathological lesions. Surgical procedures should be aimed at increasing the space beneath the coraco-acromial arch to reduce wear on the rotator cuff. PMID- 1745541 TI - [2 roentgen projections for the subacromial space before and following acromioplasty. Results of a study series of 40 patients]. AB - It is suggested that two radiological projections of the scapula, an AP view and a lateral (tunnel) view, be obtained in order to estimate the form and size of the acromion before and after acromioplasty. In order to evaluate the standardized films precisely, a film must have been taken for comparison before the surgery. As the method described is easily reproducible, it can be used to evaluate the effect of an acromioplasty irrespective of whether the procedure was an open or an arthroscopic one. The radiological results can be correlated with the functional results at the beginning of rehabilitation and at the end of this period. More sophisticated studies might require a more elaborate X-ray technique than the one proposed in this article. PMID- 1745542 TI - [Reconstruction of massive rotator cuff rupture using a deltoid muscle flap]. AB - In extensive rotator cuff tears with rupture of the supra- and infraspinatus muscles, we have obtained good and very good results persisting for 3 years or longer only in 40% of cases treated by resection and debridement, and in 25% of our cases the head of the humerus was found to be no longer centrally located in the joint socket on X-ray examination 10 years after treatment. It was therefore proposed that an active muscle flap taken from the anterior part of the deltoid muscle (part III according to Fick) should be used to span the trophic defect in the rotator cuff, being sutured into healthy tissue following freshening up. This seems logical, since the transferred muscle flap remains innervated and vascularized and also works synergistically with the rest of the rotator cuff. The flap interposed in this way between the greater tubercle of the humerus and the acromion functions in the same way as a double-bellied muscle and prevents displacement of the head of the humerus. In this way an active rotator cuff is produced, which also takes over the function of stabilizing the humeral head. After follow-up of at least 1 year (average 19 months), the result is aesthetically satisfactory in all 50 shoulders treated in this way; 47 are free of pain or painful only some of the time; in 32 active elevation of over 120 degrees is possible; 21 have symmetrical force ratios in elevation and 15 for outward rotation in 90 degrees abduction. All reconstructed shoulders were characterized by fatigability in elevation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745543 TI - Shoulder arthroplasty today. PMID- 1745544 TI - The adaptation of three isolates of Babesia divergens to continuous culture in rat erythrocytes. AB - Three isolates of Babesia divergens have been cultured continuously for 6 months in rat erythrocytes using the candle jar technique (Trager & Jensen, 1976). One isolate was already rat-adapted, the other two became adapted to rats through continuous culture in rat erythrocytes. Parasites were cultured in rat erythrocytes in RPMI medium supplemented with 20% foetal calf serum. The highest parasitaemia obtained was 35% and multi-parasitization of red blood cells was often observed. Cultures of B. divergens remained infective to splenectomized rats. Cultures with high parasitaemias contained a large number of extracellular merozoites. When separated from the red blood cells, these extracellular merozoites retained their infectivity. PMID- 1745545 TI - Transfer of Eimeria apionodes from wood mice (Apodemus sylvaticus) to laboratory mice (Mus musculus). AB - Transfer of Eimeria apionodes from wood mice directly into untreated laboratory mice was unsuccessful but transfer into corticosteroid-treated animals produced an oocyst output, about 1000 times less than that observed from wood mice after a similar inoculum. Repeated passage through corticosteroid-treated laboratory mice resulted in a line adapted to survival in untreated animals. This line was compared with the parent strain maintained in wood mice and some features of the oocyst output patterns, notably the pre-patent period, appeared to be controlled by the host species. The oocyst production of each population was higher in the host species to which it was adapted than in the other host species (P less than 0.001). Once adapted to laboratory mice, the line produced insignificantly different levels of oocysts in corticosteroid-treated and untreated animals (P greater than 0.05). PMID- 1745546 TI - Ultrastructural changes associated with reversal of chloroquine resistance by verapamil in Plasmodium chabaudi. AB - Reversal of chloroquine (CQ) resistance by verapamil, a Ca2+ antagonist, has been shown in CQ-resistant human and rodent malaria parasites. Here, we report ultrastructural changes associated with this phenomenon in CQ-resistant Plasmodium chabaudi (AS strain) after infected mice were administered CQ and verapamil. At parasitaemias of 5-7%, CQ at 6 mg/kg caused little morphological effect on CQ-resistant parasites. In contrast, co-administration of CQ and verapamil at 50 mg/kg induced swelling of food vacuoles with clumped pigment at 2.5 h. Morphological changes other than food vacuole enlargement occurred at 21 and 45 h: disappearance of endoplasmic reticulum, formation of myelin structures, focal cytoplasmic vacuolization and coarse clumping of electron-dense material in nuclei. These structural changes appeared to be very similar to those observed in CQ-sensitive P. chabaudi in mice injected with CQ alone or CQ plus verapamil. On the other hand, verapamil at 50 mg/kg alone did not induce any effect on both CQ sensitive and CQ-resistant P. chabaudi. These results suggest that swelling of the food vacuoles is an initial event associated with reversal of CQ-resistance by verapamil. PMID- 1745547 TI - Evidence for translational control of beta-tubulin synthesis during differentiation of Leishmania donovani. AB - Tubulin biosynthesis was rapidly induced during transformation of the mammalian (amastigote) stage of the kinetoplastid parasite Leishmania donovani to flagellated promastigotes. However, transcription of beta-tubulin genes occurred constitutively, as judged by nascent RNA synthesis in isolated nuclei and Northern blotting of steady-state mRNA. Two mRNA species of 2.2 and 2.4 kb were shared by the two cell-types, while a third 2.6 kb species, constituting about 20% of the total, was present in large amounts in promastigotes. RNase protection experiments demonstrated sequence microheterogeneity in the 5'-untranslated region, the pattern of which was identical in promastigotes and amastigotes. By primer extension assays, heterogeneity in the 5'-terminal cap structure of amastigote beta-tubulin mRNA and differential pausing of reverse transcriptase within the mini-exon leader region were detected. These differences correlated with enhanced translational efficiency of tubulin mRNA from promastigotes in a rabbit reticulocyte lysate system. The results indicate that translational control plays a major role in tubulin induction during L. donovani differentiation. PMID- 1745548 TI - The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (alpha 1 and omega 1) from Schistosoma mansoni eggs. AB - T cell-deprived mice acutely infected with S. mansoni suffer microvesicular hepatocyte damage which is not seen in infected, immunological intact animals. A cationic fraction (CEF6) of the PBS-soluble portion of S. mansoni eggs (SEA) induces antibodies which, on passive transfer, prevent hepatocyte damage. CEF6 contains 2 antigens, omega 1 and alpha 1, and has also been shown to be a useful serodiagnostic reagent. This paper describes the purification and characterization of the 2 antigens present in CEF6. omega 1 is a monomeric glycoprotein with a pI greater than 9.0 and a molecular weight of 31 kDa. Alpha 1 consists of two immunologically cross-reactive dimers, 41 and 36 kDa in non reducing conditions, each of which consists of one unique and one common glycoprotein subcomponent. In ELISA with mouse and human infection sera omega 1 is shown to be S. mansoni specific and is better able to distinguish S. mansoni infections from other schistosome infections than are unfractionated SEA, CEF6 or alpha 1. Passive transfer of monospecific anti-omega 1 sera into S. mansoni infected, T cell-deprived mice completely prevented the occurrence of microvesicular hepatocyte damage in these animals. Monospecific anti-alpha 1 serum had no hepatoprotective capacity. PMID- 1745549 TI - Culture characteristics of Trypanosoma catostomi and Trypanosoma phaleri from North American freshwater fishes. AB - Culture characteristics of two species of piscine trypanosomes were compared. Trypanosoma catostomi from Catostomus commersoni was isolated in hypo-osmotic blood agar media but not in hyper-osmotic media. However, T. phaleri from Amia calva was isolated in both media. Only T. catostomi was stimulated to divide by diluting infected blood with water. The maximum number of T. phaleri and percentage of trypomastigotes were not affected by NaCl concentration. The maximum number of T. catostomi was inversely related to osmotic pressure and the percentage of trypomastigotes was directly related to osmotic pressure. This was confirmed by using equi-osmotic concentrations of NaCl, NaBr, Na acetate, KCl, choline-Cl or sucrose. Supplementation with urea had no effect on the number or morphology of trypanosomes. The survival of T. catostomi following cryopreservation was enhanced by prior incubation in hyper-osmotic media. Differential culture characteristics of these species may reflect adaptation to different host-vector systems. PMID- 1745550 TI - Reduced accumulation of isometamidium by drug-resistant Trypanosoma congolense. AB - The accumulation of the trypanocide isometamidium chloride (Samorin, RMB Animal Health Ltd., UK) by a range of clones of Trypanosoma congolense with varying sensitivity to the drug, was measured by methods based on the fluorescence of isometamidium. Fluorescence microscopy and flow cytometry showed a reduction in drug accumulation by resistant clones. Fluorescence spectrophotometry demonstrated an inverse correlation between the intensity of cell-associated fluorescence and the level of resistance of the clones expressed in vivo. The addition of the metabolic inhibitor SHAM/glycerol to the incubation medium resulted in a reduction of this apparent difference in drug accumulation between the clones; those clones which were sensitive to isometamidium showed a reduction in fluorescence while a percentage increase in fluorescence was observed as clones became more resistant to the trypanocide. These observations may be of value for the in vitro detection of resistant T. congolense populations and may also be used to estimate the mean level of resistance in a given sample. The results also imply that decreased accumulation of isometamidium by drug-resistant clones of the parasite may be responsible for the reduction in sensitivity. PMID- 1745551 TI - Intra-uterine larval development of the polystomatid monogeneans, Pseudodiplorchis americanus and Neodiplorchis scaphiopodis. AB - Larvae of the monogeneans Pseudodiplorchis americanus and Neodiplorchis scaphiopodis develop within egg capsules retained in the uterus of the parent parasite. This study reveals adaptations for the storage and nutrition of infective stages which have no known precedent amongst other platyhelminths. The vitelline system is greatly reduced and appears to contribute little to embryo nutrition. An electron-dense 'shell' which encloses the newly formed embryos is subsequently replaced by a thin flexible sac composed of concentric layers of membranes which are derived from the uterus wall. Further membranes are added to this multi-laminate structure as the encapsulated embryos pass along the uterus, and this enables the sac to expand continuously as the larva inside it grows. The capsule lining extends into fine cytoplasmic processes which 'plumb in' to the larval tegument between ciliated cells. These connexions are packed with glycogen and appear to perform a placenta-like function. The unique adaptations correlate with the demands of the life-cycle. Large numbers of oncomiracidia (up to 300) can be packed, in membranous sacs, within the storage capacity of the uterus; direct transfer of nutrients from parent to offspring enables resources to be supplied over an extended period; and infective larvae can be maintained in readiness for an unpredictable opportunity for transmission. PMID- 1745552 TI - Ultrastructure and microanalyses of the protoscolex hooks of Echinococcus granulosus. AB - The rostellar distal cytoplasm of Echinococcus granulosus protoscoleces is characterized by extensive basal membrane infolding, prominent hemidesmosomes and is subtended by a lamina reticularis with microfibrils of approximately 10 nm diameter that occasionally show a 55 nm banding periodicity. The rostellar hooks, in 2 rows, each have a blade, guard and handle region and possess a central amorphous pulp, a middle microfibrillar medulla with microfibrils of approximately 4 nm diameter, and a complex outer cortex in all but the proximal region of the guard and the base of the handle. In these regions additional material, of similar electron density to the medulla, but lacking the fibrillar substructure, occurs and gives the areas a lobed appearance. Energy-dispersive X ray microanalysis of whole hooks demonstrated the presence of sulphur and trace quantities of phosphorus. X-ray near-edge absorption spectra resembled those of cystine, feather and hair and showed the sulphur to be predominantly in the form of disulphide linkages. X-ray diffraction patterns of whole hook preparations revealed 2 diffuse rings with equatorial spacings of 7.99 A and 15.22 A, thus differing from vertebrate keratins. PMID- 1745553 TI - Immunocytochemical and radioimmunometrical demonstration of serotonin- and neuropeptide-immunoreactivities in the adult rat tapeworm, Hymenolepis diminuta (Cestoda, Cyclophyllidea). AB - Standard indirect immunocytochemical techniques have been interfaced with confocal scanning laser microscopy (for whole-mount preparations) and epifluorescence microscopy (for cryosections) to investigate the occurrence and distribution of serotoninergic and peptidergic nerve elements in adult H. diminuta. Serotonin (5-HT)-immunoreactivity (IR) was widespread throughout the worm, occurring in the paired cerebral ganglia, transverse commissure, the 10 longitudinal nerve cords and in a plethora of small nerve fibres of the peripheral nervous system. An abundance of serotoninergic nerve cell bodies was found in association with the lateral nerve cords. The genital atrium and accessory reproductive ducts were richly innervated with serotoninergic nerve fibres. Thirty-five antisera to 20 vertebrate regulatory peptides and 1 invertebrate peptide (FMRFamide) were used to screen the worm for neuropeptide IR. Immunostaining was obtained with antisera raised to pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP), peptide histidine isoleucine (PHI), xenopsin (XP) and FMRFamide. The most extensive pattern of IR occurred with antisera to PP and PYY, IR being evident in the cerebral ganglia, transverse commissure, longitudinal nerve cords and in small nerve fibres that ramified throughout the parenchyma. A series of bipolar nerve cell bodies between the median nerve cords displayed PP/PYY-IR. The distribution of FMRFamide-IR was reminiscent of the PP/PYY pattern but was less extensive. Comparison of the serotoninergic and peptidergic nervous systems has revealed general similarities and some distinct differences, especially with regard to the distribution of immunoreactive nerve cell bodies. Quantitative data are presented on the levels of PP-, SP-, PHI-, and gastrin-releasing peptide (GRP)-immunoreactivities demonstrable in acid-alcohol extracts of whole worms. The highest level of peptide IR determined was recorded for PP. PMID- 1745554 TI - Community control of Ascaris lumbricoides in rural Oyo State, Nigeria: mass, targeted and selective treatment with levamisole. AB - A study to compare effects of mass, targeted and selective chemotherapy with levamisole (Ketrax) as an action for the control of Ascaris lumbricoides was carried out in three communities in rural Oyo State, Nigeria. Selective treatment was applied in one village by treating the most heavily infected 20% of the inhabitants, targeted treatment in the second village involved children aged 2-15 years, while mass treatment was offered to all inhabitants excluding infants under 1 year and pregnant women in the third village. Recommended doses of levamisole were given in the villages, as described above, at 3-monthly intervals during a period of 1 year. Prevalence and intensity (epg) of A. lumbricoides infection were determined immediately before and 3 months after the period of intervention using a modified Kato-Katz technique. In the selective treatment village, no significant differences were found between the pre- and post treatment egg counts (mean (+/- S.D.) epg 6776 +/- 10,791 versus 4259 +/- 10,909 respectively) of A. lumbricoides in the total population. In the targeted treatment village, significant differences were recorded in pre- and post treatment egg counts for the total population (9057 +/- 15,797 versus 2579 +/- 6529) among the children alone (10,935 +/- 20,094 versus 992 +/- 3175) and among the untreated adults (7742 +/- 9782 versus 4561 +/- 8798). In the mass treatment village, significant differences in pre- and post-treatment egg count values were also recorded (11,907 +/- 17,220 versus 1489 +/- 5165). The intensity of Trichuris trichiura and hookworm infections among the villagers before and after intervention were not observed to have changed significantly regardless of selective, targeted or mass treatment. PMID- 1745555 TI - Evidence for the presence of quinone methide isomerase in the metacercarial cyst of Microphallus sp. (Trematoda: Microphallidae). AB - The white colour of the cyst wall of the metacercaria of Microphallus sp., even in the presence of dihydroxy phenol and phenoloxidase, is due to proteins generated through a possible quinone methide interaction. The quinone methide isomerase converts the phenoloxidase mediated quinone into beta-hydroxy catechol. Formation of catechol from quinone by cyst extracts was observed spectrophotometrically and chromatographically. This enzyme is involved in detoxification of excess quinone and beta-sclerotization of the cyst wall. PMID- 1745556 TI - Characterization of proteolytic enzymes from larval and adult Nippostrongylus brasiliensis. AB - Proteases from infective larval (L3) and adult stages of Nippostrongylus brasiliensis were investigated with a combination of techniques involving gelatin degradation and cleavage of fluorogenic substrates. Analysis of L3 excretory secretory (ES) products revealed enzymes of Mr 51, 58, 79, approximately 150 and approximately 250 kDa. Inhibition profiles indicate that the major 51 kDa protease is a metallo-enzyme. Significantly, little activity was present in larval somatic extracts, suggesting the synthesis of zymogens or precursor forms prior to secretion. Adult ES contained a distinct enzyme, of 50 kDa, and a number of other proteases were detected in somatic extracts of this stage, ranging from 51 to greater than 300 kDa. The largest of these adult somatic enzymes is also a putative metallo-protease. While nearly all enzymes from both L3 and adult are heat labile, incubation at 100 degrees C generated a previously unobserved activity at 20 kDa. Furthermore, a protease of similar size may be found in uninfected rat intestinal tissue, suggesting specific uptake of a host-associated enzyme by the parasite in the form of an inactive, heat-labile complex. PMID- 1745557 TI - A species-specific oligonucleotide DNA probe for the identification of Meloidogyne incognita. AB - A genomic library of Meloidogyne incognita Race 1 has been prepared in the bacteriophage lambda gt10 and screened for specific DNA sequences by hybridization with radio-isotope labelled total genomic DNA from a number of Meloidogyne species. One clone isolated (MR1 #15), although not totally species specific, clearly showed preferential hybridization to M. incognita. Following subcloning and sequencing of the 255 bp insert, four stretches of the sequence corresponding to oligonucleotides of approximately equal length (approximately 70 bp) were synthesized and examined for specificity. One of them, MR1 #15.2, showed the necessary specificity to be used as a diagnostic tool. PMID- 1745558 TI - Restrictions on 'multiple biochemical analyses' profiling decreases usage of biochemistry test requests. AB - One hundred and forty two thousand near-consecutive pathology episodes in a private practice laboratory were reviewed. During this period, a new government Medical Benefits Schedule (Pathology Services Table) was introduced which restricted the usage of the 'Multiple Biochemistry Analyses' (MBA) test profile. We found that requesting practitioners, when deprived of the use of the MBA profile, altered their biochemical requesting patterns and that usage of other permitted biochemical profiles increased. However, the overall use of biochemical tests decreased over the survey period, and the cost to the community of biochemical tests performed was lowered. PMID- 1745559 TI - Analgesic nephropathy in Fischer 344 rats: comparative effects of chronic treatment with either aspirin or paracetamol. AB - This study has compared the relative nephrotoxicity of chronic treatment with aspirin or paracetamol in an animal model. Changes in renal structure and urinary concentrating ability were examined in female Fischer 344 rats after continuous treatment with either aspirin (120-230 mg/kg body wt/day), or paracetamol (140 210 mg/kg body wt/day), and were compared with age-matched untreated control rats. Renal morphological changes were examined after 40-83 weeks of analgesic treatment, using light and electron microscopy. Aspirin caused renal papillary necrosis and a decrease in urinary concentrating ability, whereas paracetamol alone did not cause significant renal damage. Aspirin produced damage to the interstitial cells and matrix, particularly in the mid-papillary region, followed by changes to the thin limbs of the loop of Henle and medullary capillary endothelium. These structural changes were similar to those described previously, when continuous treatment with combined aspirin and paracetamol was studied in the same animal model. PMID- 1745560 TI - The indirect estimation of hemoglobin concentration in whole blood. AB - The present conventional methods for determination of Hemoglobin (Hb) concentration in whole blood depend on the direct colorimetric measurement of chemically modified Hb following its release from red cells by lysis. This paper examines an alternative, indirect method which does not require initial red cell lysis, corrects for the falsely elevated Hb due to the lipemic plasma and determines whether elevated WBC count effects a change in the Hb value, without the tedious laboratory manipulations currently required to correct for these artifacts. The method is simple, uncomplicated and is based on the observation of a constant ratio (2.98) between the Mean Corpuscular Volume (MCV) and the Mean Corpuscular Hemoglobin (MCH) indices obtained from standard electronic counters in use in most laboratories. The Hb concentration is calculated by the equation: [formula: see text]. The resultant Hb measurements show an acceptable degree of accuracy and precision when compared with the direct measurements obtained from a Coulter Model S + I, even in the presence of a high WBC or lipid. PMID- 1745561 TI - Quality assurance of immunodiagnostic tests in Australasia. AB - A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) in Clinical Immunology, involving 128 laboratories over a 1 yr period, revealed the following: successful participation in the program by 16 overseas laboratories (distant from Australia); only 30% of laboratories succeeded in returning their results by the scheduled date on every occasion; quantitation of urinary total protein and Bence Jones protein was poor and varied over a log scale; immunofixation was more successful in characterizing urinary paraprotein than immunoelectrophoresis; densitometry of protein electrophoresis appeared the method of choice in quantitating serum paraproteins accurately; nephelometric techniques gave better concordance between laboratories than turbidometric, radial immunodiffusion or agglutination techniques; poor concordance between laboratories in detecting weakly positive antinuclear antibodies (ANA); some laboratories had difficulties in identifying ANA patterns (only 60% of laboratories correctly identified the anticentromere pattern); few laboratories could correctly identify antibodies to extractable nuclear antigens (ENA); flow cytometry gave a smaller dispersion of lymphocyte subpopulation percentages than microscopy. A method was established to rank laboratory performance of selected tests over the 1 yr period. Such a comparative ranking scheme may alert laboratories in identifying specific or generalized deficiencies in performance. PMID- 1745562 TI - Tuberculosis in Australia: an analysis of cases identified in reference laboratories in 1986-88. AB - The Special Interest Group in Mycobacteria within the Australian Society for Microbiology has carried out a collaborative study of cases of tuberculosis diagnosed in Australian reference laboratories in the years 1986, 1987 and 1988. Annual totals of 574, 584 and 613 respectively, suggest that the incidence of bacteriologically-positive tuberculosis is continuing at 3-4 cases per 100,000 population. The highest rates were detected in males over 50 and females over 65 years of age. Three-quarters of the total cases relate to pulmonary disease. Resistance to at least 1 anti-tuberculosis drug was detected in 78 (12.7%) of isolates tested in 1988. The negligible decline in incidence of tuberculosis in Australia, the high prevalence in S.E. Asian countries, and the fact that HIV infection is an important risk factor, make it imperative that Australia's diagnostic and management programmes be maintained. PMID- 1745563 TI - Susceptibility of urine isolates of Staphylococcus saprophyticus to antimicrobial agents. AB - The minimum inhibitory concentrations (MICs) of 10 antimicrobial agents for 96 urinary isolates of Staphylococcus saprophyticus cultured from symptomatic females in the Western Australian general community are reported. All antimicrobial agents tested showed good activity, with the exceptions of norfloxacin (MIC90 8 mg/L) and ampicillin (MIC90 0.5 mg/L). Eighty-three of 96 isolates were susceptible to all antimicrobial agents tested. One isolate was resistant to both tetracycline and trimethoprim. The remainder were resistant to a single antimicrobial agent; 10 to tetracycline and 2 to trimethoprim. None of the isolates exhibited any detectable beta-lactamase activity when tested by the chromogenic cephalosporin method. Synergy between trimethoprim and sulphafurazole against Staph. saprophyticus was demonstrated in only 2 of 5 strains having an increased MIC of one or both of these agents. PMID- 1745564 TI - The hemolytic and cytolytic activity of group B streptococcal hemolysin and its possible role in early onset group B streptococcal disease. AB - The in vitro and cytolytic properties of the hemolysin of group B streptococcus (GBS) were investigated using sheep erythrocytes and McCoy cells adapted for growth in a serum-deficient medium. The relationship between the hemolysin, various carrier molecules and phospholipids was examined. Starch-based carriers interfered with the inhibitory activity of phospholipids and solvents for the phospholipids reduced the activity of the hemolysin. These technical problems were resolved by use of an albumin-based carrier, a strain producing large amounts of hemolysin and sonication of the phospholipid. The hemolysin was cytolytic for McCoy cells and this activity and its hemolytic action on sheep erythrocytes were inhibited by a number of phospholipid components of surfactant. It is possible that GBS hemolysin has a direct or indirect role in the pathogenesis of the pneumonitis of early onset GBS infection. PMID- 1745565 TI - Longitudinal studies of virulence factors of Pseudomonas aeruginosa in cystic fibrosis. AB - Among 111 strains of Pseudomonas aeruginosa from 49 children with cystic fibrosis, duration of colonization correlated with bacterial phenotype. We confirmed that P. aeruginosa from chronically colonized patients tended to be less motile, produce lower levels of protease and elastase, to be more sensitive to normal serum and to be polyagglutinating or untypable with standard antisera. We also showed that phospholipase and heat-stable hemolysin, concerned in metabolism of inorganic phosphate, and exotoxin A, were lower in these isolates. In longitudinal studies there was a decrease in virulence properties when isolates from the same patient were compared. No reversion from altered phenotype to 'wild-type' characteristics was found. PMID- 1745566 TI - Is primary sensitivity testing on urine samples valid? AB - One thousand eight hundred urine specimens were examined prospectively to determine the validity of primary sensitivity testing. Microscopic criteria assessing pyuria and microorganisms were developed for predicting the presence of urinary tract infection and thus suitability for direct sensitivity testing. The criteria selected gave a positive predictive value of 74.6% and a negative predictive value of 99.5%. Zone diameters by primary and standardized secondary methods were compared for each urinary pathogen to each antibiotic tested. Percentage agreement between primary and secondary sensitivity results varied between 100% for Enterobacteriaceae tested against Gentamicin to 95.2% for Enterococcus faecalis tested against Ampicillin. Seventeen discrepancies between primary and secondary test results were observed (error 2.0%) with only 3 of potential clinical significance (primary sensitive, secondary resistant). Although primary sensitivity testing has limitations, our study indicates that the results are, in the vast majority of cases, in agreement with secondary testing, and are probably adequate for the clinical management of uncomplicated urinary tract infections. Furthermore, as primary testing rarely produces false resistant results it may permit earlier modification of initial empiric therapy. PMID- 1745567 TI - Relationship between clinical and milk isolates of Yersinia enterocolitica. AB - In the summer of 1987-1988, an outbreak of 11 cases of Yersinia enterocolitica enteritis caused by 2 serogroups (0:3, 0:6,30) occurred prompting an investigation into possible environmental sources. Symptoms were present for a mean of 9 days and occurred in 2 distinct age groups--toddlers (7) who presented with diarrhea, and young adults (4), 3 of whom presented clinically with appendicitis. In a survey of 39 randomly chosen pasteurized milk samples, 9 were positive for growth of Y. enterocolitica and 1 each for Y. fredericksenii and Y. intermedia. An association between clinical and milk isolates of Y. enterocolitica was thus sought by comparison of biogroups, serogroups, virulence markers and biochemical and outer membrane profiles. All milk isolates belonged to biogroup 1, serogroup 0:6,30. Pathogenicity studies on the 0:6,30 serogroup isolates from feces and milk were performed with 3 in-vitro tests (Ca2+ dependency, autoagglutination, & serum resistance). The human isolates were positive in most of the 3 tests whilst none of the milk isolates were positive. Outer membrane protein analysis of 0:6,30 from human and milk isolates showed similar profiles suggesting a possible association, however the environmental source of the majority of isolates (0:3) remains unknown. PMID- 1745568 TI - Utility of the polymerase chain reaction (PCR) for prenatal diagnosis of genetic disease. AB - Gene amplification by the polymerase chain reaction (PCR) has been applied to prenatal diagnosis for alpha and beta thalassemias (1 and 5 cases respectively), Hemoglobin (Hb) Lepore/beta thalassemia (1 case) and cystic fibrosis (14 cases). Chorionic villus samples were obtained in the tenth week of pregnancy and DNA analysed in parallel with conventional gene mapping. Direct diagnosis of the common Mediterranean beta-thalassemia mutations (IVS-1-110 and codon 39), Hb Lepore, and the delta F508 mutation causing cystic fibrosis was achieved by hybridization of amplified material with pairs of allele-specific oligonucleotide (ASO) probes or by restriction enzyme digestion of PCR products. Results were confirmed by DNA mapping. Definitive diagnosis or exclusion of an affected fetus was possible in 17 of 21 cases thus examined. PCR reduces the time required for prenatal diagnosis. DNA contamination is a potential source of error. PMID- 1745569 TI - Ovarian follicular non-Hodgkins lymphoma. AB - Non-Hodgkins Lymphoma presenting in and confined to the ovaries is a rare occurrence. A follicular histological pattern has been reported only occasionally in this setting. A case of follicular mixed small cleaved and large cell lymphoma, discovered incidentally and limited to the ovaries is reported. Immunological marker studies revealed a monoclonal population of B lymphocytes with surface Ig A Kappa. A review of cases in the literature suggests that follicular histology in stage I ovarian disease confers an outcome similar to that for follicular nodal disease. PMID- 1745570 TI - Poems syndrome. AB - A 40 year old Chinese woman presented with anasarca and later developed features of POEMS syndrome. These are peripheral neuropathy (P), organomegaly (O), endocrine dysfunction (E), monoclonal gammopathy (M), and skin changes (S) which are usually associated with plasma cell dyscrasia. In our patient, monoclonal gammopathy was not detected on immunofixation electrophoresis and was revealed only after analysis of kappa/lambda light chain ratio of the raised serum IgA immunoglobulin. Needle liver biopsy of her grossly enlarged liver showed marked accumulation of glycogen and presence of giant mitochondria in the hepatocytes, a feature not previously reported. PMID- 1745571 TI - A tree-structure model for analyzing laboratory test costs. AB - A method of costing clinical laboratory tests is described in which total laboratory costs are apportioned into 3 components: an 'organizational overhead cost' to describe the cost of running an organization; a 'cost per episode' to describe the costs incurred per request; and a 'cost per test' to describe the actual analytical costs of tests performed. A tree-like structural model is described which allows for distribution of this 'cost per test' component to the contributing tests and the calculation of the true 'cost per test'. The implementation of this model on a computer spreadsheet has been achieved. When combined with the other cost components, the true total costs of laboratory testing can be determined for any particular test. The model also allows calculation of the incremental and marginal costs of a test and permits optimization of laboratory test frequencies and work-load to minimize laboratory analytical costs. PMID- 1745572 TI - Should we bury the autopsy? PMID- 1745573 TI - Adrenal cortical tumors in childhood--clinicopathological features of six cases. AB - Six cases of adrenal cortical tumors are presented with a discussion of the clinical features and histological findings. Five of the 6 children, aged between 6 mths and 6 yrs, presented with symptoms of hyperadrenalism, 4 with virilization and 1 with Cushingoid features. The remaining infant presented with an asymptomatic abdominal mass. In each case there was a unilateral tumor separated from the residual adrenal gland by a thin fibrous capsule. Surgical resection was the treatment employed and, in the 5 cases with functional tumors, perioperative hydrocortisone was given. None of the children received post-operative chemotherapy or radiotherapy. Bizarre cellular morphology, a high mitotic count and extensive necrosis were all seen in clinically benign disease, demonstrating not only the efficacy of local resection but also the difficulty in applying the usual histological criteria of malignancy to these pediatric adrenal tumors. At follow-up, 5 of the 6 patients are alive with no evidence of recurrent disease. The only death resulted from measles pneumonitis in the 1 child who presented with Cushing's syndrome. PMID- 1745574 TI - Effect of smoking cessation on serum apolipoprotein A-I and A-II concentrations. AB - This study investigated the effects of 6 weeks' smoking cessation on serum levels of total-cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and apolipoproteins A-I and A-II (apo A-I and apo A-II) in 64 subjects of both sexes. Smoking cessation was associated with an increase in levels of apo A-II. Concurrent changes in weight and alcohol consumption during attempted smoking cessation, together with change in thiocyanate level, were entered as predictor variables into a multiple regression analysis. The change in apo A-II was found to be best accounted for by change in plasma thiocyanate level, and, in women, change in HDL-C and apo A-I by change in weight. The changes induced by smoking cessation may be due, at least in part, to associated changes in alcohol consumption and/or dietary intake, but in the case of apo A-II there is evidence of a more direct effect. PMID- 1745575 TI - [Descriptive epidemiology from autopsies at the Ospedale Maggiore di Milano from 1986 to 1987]. AB - Descriptive epidemiology of autopsies performed at Ospedale Maggiore in Milan 1986-87. With the aim of setting up an autopsy database we have processed and stored data relating to diagnoses from autopsies performed over the two-year period 1986-1987 at Ospedale Maggiore in Milan. We used a program developed on the basis of indications provided by a group of pathologists working in various centres in Italy. The program is designed to include the storage of personal details, clinical diagnoses, autopsy diagnoses, and a semi-automatic procedure for apposition of SNOMED codes. Using this stored material, statistical studies have been carried out on the sample of autopsy subjects and the incidence of the various types of pathology; also, a comparative evaluation has been made between the clinical diagnoses of the cause of death and those derived from autopsy. It appears that clinicians tend to overdiagnose neoplastic diseases and underestimate the significance of cardiocirculatory pathologies. Our data confirm that in spite of the advances in diagnostic technology, autopsy maintains its value and importance as a diagnostic tool, especially for its quality-control role in the public health field; moreover it can also play a significant part in epidemiological studies. PMID- 1745576 TI - [Atheroembolism: a form of systemic vascular disease]. AB - Atheroembolism, a systemic vascular disease. Cholesterol crystal embolization (CCE) is an infrequent but serious disorder that is often an unrecognized medical problem. CCE may occur spontaneously from eroded atherosclerotic plaques or most frequently following procedures such as angiography, angioplasty, cardiac catheterization, anticoagulant therapy and aortic surgery. CCE predominantly affects elderly males with a frequent history of hypertension, atherosclerotic vascular diseases and renal insufficiency. CCE may result in protean clinical manifestations and may produce a spectrum of functional impairment. Confusion over the disease's natural history arises because the difficulty of establishing an antemortem diagnosis, and because the laboratory findings are non-diagnostic and non-specific. The mortality was 81% and the causes of death was most often due to multiorgan failure especially renal involvement. The definitive diagnosis depends upon finding the presence of intravascular cholesterol crystal in biopsy or autopsy specimens. The skin, muscle and kidney were the three most common sites for obtaining a premortem diagnostic biopsy. PMID- 1745577 TI - [Comparative morphological study of the structure of the normal and arteriosclerotic internal mammary, coronary, and renal artery wall]. AB - Morphological comparative study of the normal anatomy of the internal mammary artery, coronary artery and renal artery, and their atherosclerotic alterations. We report in this paper the comparative results of a morphological and morphometrical study of the normal anatomy of the Left Coronary Artery (interventricular descending branch) (LCA), Internal Mammary Artery (IMA) and Renal Artery (RA) and their atherosclerotic alterations in 27 unselected people of both sexes aging from 19 to 76 years (average 59 +/- 14.3). Sections from three different segments of each vessel were examined by measuring the thickness of the intima and media calculated at the maximum intimal thickening. The lumen was also measured at the level of its highest pathological reduction; the same measurements were carried out on sections free from atherosclerotic damage. Then the intima to media ratio was assumed as major indicator of atherosclerosis involvement according to the literature. All these parameters were statistically analysed. With these procedures we found that LCA displayed more severely atherosclerotic changes than IMA. The degree of damage in RA fell in between when compared to the other arteries. The intima to media ratio average was 0.061 mm. (+/- 0.084) in I.M.A.; 0.882 mm. (+/- 0.753) in L.C.A. and 0.272 (+/- 0.315) in RA with statistically significant differences between IMA and LCA (p less than 0.001) and between IMA and RA (p less than 0.001). In the lesion free sections intima to media ratios were 0.178 (+/- 0.90) in LCA, 0.053 (+/- 0.28) in IMA and 0.082 (+/- 0.127) in RA. The difference was statistically significative between LCA and IMA, but not between RA and IMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745578 TI - [Histopathological parameters and lymphatic metastasis in supraglottic laryngeal carcinoma]. AB - Histopathologic parameters in predicting lymph node metastasis of supraglottic laryngeal carcinoma. A systematic clinical-pathological study was performed on fifty-three resected cases of supraglottic laryngeal squamous cell carcinoma, followed up for at least 5 years. The aim of the research was to evaluate histopathologic parameters in predicting lymph node metastasis (N+) as expression of biological malignancy of the neoplasm. The following neoplastic microscopical features were studied: histopathologic and cytologic grading, pattern of growth, peritumoral inflammatory infiltrate, stromal reaction, tumoral necrosis. The results are as follows: stromal reaction and cytologic grading are not useful to identify N+ and N- cases. Cases with high and low degree of differentiation (Broder's grading) are significantly correlated respectively to low (14.3%) and high (70%) incidence of lymph node metastasis (p less than 0.03). A clear correlation is present between the pattern of growth "pushing" and lacking of node metastasis (84.6%). A favorable prognosis significance seems to be linked with the presence of peritumoral lymphoplasmocytic infiltrate, which results to be a marker of cases in which lymph node metastasis incidence is very low (5.5%; p less than 0.001). On the contrary lymph node metastasis incidence increase when tumoral necrosis is present (76.5%; p less than 0.001). PMID- 1745579 TI - [Ovarian metastases of extragenital tumors. Anatomo-pathological contribution to their interpretation]. AB - Ovarian metastases from extragenital malignant tumours. An anatomohistopathologic approach. 102 cases of ovarian metastases from extragenital malignant non hematopoietic primaries have been studied in the Institute of Anatomy and Histopathology of the Trieste University. Breast cancers, followed by colonic, gastric and pancreatic tumours are the most frequent spreading primaries to the ovaries. Generally speaking the ovarian metastases seems to be closely related to the lower age at the tumour onset and to the width of metastatic spreading; this is true mainly for breast and colorectal cancer. These features should suggest that tumour aggressiveness, rather than some tropism of malignant cells, could play the most important role in the metastatic involvement of ovaries. A double behaviour should be instead suggested for gastric cancer: the first one is consistent with those previously described for the other tumours, the second one is related to a less aggressive gastric cancer, arising in the elderly (mean age 73 years old) with isolated involvement of the ovary showing the features of Krukenberg tumours. PMID- 1745580 TI - [Recurrent benign intrahepatic cholestasis. Description of 3 cases]. AB - Benign recurrent cholestasis. Report of three cases. 3 cases of benign intrahepatic recurrent cholestasis are reported. The disease is very rare and both clinical and pathological features are necessary for the right diagnosis. The value of liver biopsy in excluding other icteric diseases is stressed; clinical and serological findings are also important for the diagnosis and for the management of the patient. PMID- 1745581 TI - Cytological features of a craniopharyngioma. AB - The fine needle aspiration cytology of a cystic suprasellar lesion, which caused bilateral hemianopia in a woman aged 63, resulted to be consistent with a craniopharyngioma and was confirmed by tissue diagnosis. The cytological pattern showed macrophages and debris with calcifications indicating the presence of a cyst. Furthermore squamous cells of basal type and ghost cells were identified. These findings together with the seat of the lesion allowed for the diagnosis of craniopharyngioma and for the differentiation from other cystic lesions of the same region. The case confirms the value of the fine needle aspiration cytology in the detection of craniopharyngioma and points out cytological peculiarities of this not rare neoplasm. PMID- 1745582 TI - [Primary rhabdomyosarcoma of the cerebellum. Histopathological and immunohistochemical study of an autopsy case]. AB - Primary rhabdomyosarcoma of the cerebellum. Histopathological and immunohistochemical study: a necropsy case. A necropsy case of primary cerebellar rhabdomyosarcoma occurred in a 38-year-old man has been investigated by histological and immunohistochemical techniques. In the most differentiated rhabdomyoblasts microscopic analysis showed obvious cross-striations and immunohistochemical reactivity for myoglobin (PAP method). Many tumor cells were positive for vimentin and muscle-specific intermediate filament protein desmin, but neither for glial fibrillary acidic protein nor neuron-specific enolase. The diagnostic role of the immunohistochemistry in this tumor is pointed out. The clinicopathological features of 30 cases of primary rhabdomyosarcoma of the central nervous system previously reported in the literature are briefly reviewed, and the histogenesis is discussed. PMID- 1745583 TI - Primary malignant lymphoma of the central nervous system. Case report. AB - We report a case of primary malignant lymphoma of the central nervous system found in a 69-year old woman suffering from Parkinson's disease and hypertension. The CAT scan revealed an ill defined lesion in the left frontal lobe which at surgery appeared as a brownish-black friable neoformation. The histologic exam revealed a proliferation of voluminous round lymphoid cells with 2 or 3 nucleoli often apposed to the nuclear membrane. At the immunohistochemical investigation they were positive for LC and L26 monoclonal antibodies. Malignant centroblastic B-cell lymphoma was diagnosed. All post-surgery investigations excluded the presence of neoplasms in other sites. PMID- 1745584 TI - Acute idiopathic interstitial giant cell myocarditis. A histological and immunohistological study of a case. AB - The Authors report on a case of acute idiopathic giant cell myocarditis, which occurred in a young man without previous history of immunodeficiency or tumours, and displayed a rapidly fatal clinical course. Autoptic examination showed diffuse damage to the myocardium, with myocytolysis, granuloma formation and abundant giant cell reaction. No significant changes were observed in the other organs and systems . Immunohistochemistry revealed that the giant cells strongly reacted with the antibody KP1--raised to the macrophage-associated antigen CD68- whereas they did not stain with the monoclonal against the muscle-specific marker desmin. In the light of their findings and previous reports in the literature, the Authors discuss the possible origin of giant cells, along with the pathogenesis of the condition. PMID- 1745585 TI - Bizarre angiomyomas of superficial soft tissues. PMID- 1745586 TI - Michael Faraday--putting perception in its place. PMID- 1745587 TI - Perceived depth scales with disparity gradient. AB - Perceived difference in depth between two adjacent stimuli decreases with increasing disparity gradient even if the disparity stays constant, ie when the stimuli approach each other along paths within fronto-parallel planes. This depth scaling effect is more pronounced with line stimuli than with two isolated points or two small symbols and is insignificant for easily discriminable symbols. The decrease in perceived depth is more pronounced for horizontal orientation than for oblique or vertical orientation. The ratio of perceived depth difference to displayed disparity difference also decreases when the distance between the stimuli increases at a constant gradient in depth. This is to say that we are more correct in our depth estimates for steep gradients in depth when the euclidean distance between the stimuli is short. PMID- 1745588 TI - Conflicting figure--ground and depth information reduces moving phantom visibility. AB - Moving phantom visibility was measured in two experiments where the global figure ground and depth relations within phantom-inducing patterns were manipulated. The local inducing environment where the illusion occurred was identical for all patterns. Phantom visibility was significantly reduced when occlusion cues specified the phantom-inducing parts of a pattern as ground. These results suggest conflicting figure-ground and depth information interferes with the representation and perception of phantoms as figure regions. PMID- 1745589 TI - Similarity of tactual and visual picture recognition with limited field of view. AB - Subjects attempted to recognize simple line drawings of common objects using either touch or vision. In the touch condition, subjects explored raised line drawings using the distal pad of the index finger or the distal pads both of the index and of the middle fingers. In the visual condition, a computer-driven display was used to simulate tactual exploration. By moving an electronic pen over a digitizing tablet, the subject could explore a line drawing stored in memory; on the display screen a portion of the drawing appeared to move behind a stationary aperture, in concert with the movement of the pen. This aperture was varied in width, thus simulating the use of one or two fingers. In terms of average recognition accuracy and average response latency, recognition performance was virtually the same in the one-finger touch condition and the simulated one-finger vision condition. Visual recognition performance improved considerably when the visual field size was doubled (simulating two fingers), but tactual performance showed little improvement, suggesting that the effective tactual field of view for this task is approximately equal to one finger pad. This latter result agrees with other reports in the literature indicating that integration of two-dimensional pattern information extending over multiple fingers on the same hand is quite poor. The near equivalence of tactual picture perception and narrow-field vision suggests that the difficulties of tactual picture recognition must be largely due to the narrowness of the effective field of view. PMID- 1745590 TI - Retinal mechanisms in the perception of subjective contours: the contribution of lateral inhibition. AB - One mechanism frequently proposed for the creation of subjective contours and their related brightness effects involves lateral neural interactions on the retina, such as the lateral inhibitory effects that underlie brightness contrast. Subjective contour stimuli were displayed under an intermittent light source, with rapid onset and slow offset as has been shown to increase lateral inhibitory interactions by allowing summation of neural onset transients. A sample of forty subjects, using magnitude estimates, reported increased subjective contour clarity and brightness effects under these exposure conditions. The effects were larger for relative brightness differences than for contour visibility. It appears that this technique may have applications in exploring retinal contributions to other aspects of the perception of subjective contours. PMID- 1745591 TI - Figural conditions affecting the formation of anomalous surfaces: overall configuration versus single stimulus part. AB - Two kinds of figural condition affecting the formation of anomalous surfaces were examined in three experiments. The strengths of two factors (figural incompleteness and width of the inducing areas) were compared in order to determine: i) which of the two factors is more effective in the creation of the illusion, and ii) whether the inducing-area width is so important that it can also destroy the illusion when the inducers are clearly incomplete or 'gappy'. The results show that the inducing-area width seems to predominate over figural incompleteness in the formation of anomalous surfaces. PMID- 1745592 TI - Anomalous contours and illusion of angularity: phenomenal and theoretical comparisons. AB - Many experimental comparisons between real and anomalous contours have proven the functional equivalence of the two conditions; however, there are some contradictory findings. One of these is obtained by analyzing the anomalous contours in the light of a new illusion, called the 'illusion of angularity'. A circle becomes a polygon when it covers the centre of a radial arrangement of black stripes, and a polygon changes its perceptual shape depending on its orientation with respect to the same radial arrangement. Phenomenally, it appears like a very pointed polygon, in which every side is concave or, alternatively, a shape that looks like a circle with angles added in the spaces between the radial stripes, or a polygonal shape in which every side is convex. The reciprocal anomalous counterparts of these conditions, obtained by removing the geometrical/polygonal contours, reveal different results. In the first case, one sees a perfect circle; in the second case, a polygon with blunted vertices, or a circular shape with angular protrusions; in the third case, a deformed circle. These results are inconsistent with some theoretical models proposed to explain the emergence of anomalous contours, namely, all the top-down models expressed in terms of cognitive constructions and perceptual hypotheses, or in terms of global figural organizations. Rather, these comparisons suggest a different interpretation for the two phenomena (the illusion of angularity and anomalous contours). This interpretation is based on dynamic interactions or on network computations that synthesize both real and anomalous contours. PMID- 1745593 TI - A dynamic model for anomalous figures: the shape of line-induced brightness modifications. AB - It is recognized that a fundamental role in the perception of anomalous figures is played by the intensity and shape of brightness modifications induced by line ends. The aim of this work was to study the structure of these modifications experimentally, by using variously arranged dots as probes. It was thus assumed that dots can measure activations generated inside abrupt line ends. The results show distribution of activation which differs according to dot distance and angle with respect to the continuation of the line near its end. These data do not agree with the predictions of information processing models in the literature on anomalous figures, which are based on perceptually postulated figures accounting for unlikely gaps. However, they do agree with the dynamic model proposed here, which is based on the idea that certain figure characteristics, eg the differential brightness of anomalous figures, depend on activation distribution which in turn depends on the organization of the forces in play. This idea is rooted in Gestalt theory. Another model supported by our experimental data is Grossberg's neural dynamic approach. In this case too, the basic idea is that of activation distribution which depends on the interaction of complex neural networks functioning according to special algorithms. PMID- 1745594 TI - Evidence for independent processing of subjective contour brightness and sharpness. AB - Subjective contours have been of considerable interest because of their importance to theories and physiological models of form perception. In particular, they have recently been characterized as the result of magnocellular cortical processing. There is, however, a paucity of parametric data relating to basic psychophysical parameters in this field. Two experiments are reported in which the roles of subjective contour size, retinal eccentricity, and flicker rate in subjective contour salience were investigated. Eleven observers estimated subjective contour magnitude using an Ehrenstein configuration. Configurations ranging in size from 0.25 to 3 deg were presented to three retinal loci (fovea, 2 deg, and 4 deg) at flicker rates ranging from 5 to 15 Hz. Subjective contour brightness and distinctness were measured separately. Brightness was greatest at a subjective contour size of about 1.25 deg, at flicker rates of 5-7 Hz, and at 3 deg peripheral for all flicker rates and all but the smallest stimulus sizes. Distinctness decreased with eccentricity and flicker, but remained high at small diameters (thus implicating spatially sensitive mechanisms). Taken together, the results support a magnocellular processing of subjective contours with respect to brightness, but also suggest that there is a parvocellular contribution to subjective contour sharpness. PMID- 1745595 TI - Visual illusory productions with or without amodal completion. AB - A new type of illusory contour is presented whose appearance is generated by the graphic representation of groups of human figures interacting in a coordinated manner with external reality. When numerous pictorial indicators of cause-effect relationships are provided, and appropriate techniques and sufficiently ambiguous observation conditions are used, hallucinatory objects congruent with expectations linked to the meaning of the configurations appear. There is thus a high-level semantic component that is active in the formation of visual illusory contours and is even capable of interacting with other known factors: brightness contrast, the number of elements, the degree of alignment of the elements, etc. This new type of illusory contour fits current definitions and can be experimentally modified. The variations in subjective clarity scores are presented for a study in which twenty subjects observed nineteen experimental figures, certain variables of which were manipulated. The issue is worthy of further experimental investigation. PMID- 1745596 TI - Illusory figures based on local kinematics. AB - A new type of motion-induced illusory figure determined by local kinematic information is investigated. The new figure is induced by radial line patterns subjected to either figure motion (the lines change as if they were stationary and a triangle was rotating in front of them) or background motion (the lines change as if they were being rotated behind a stationary triangle). Although the two kinds of motion are equivalent from the viewpoint of relative displacements, perceptually they yield very different results. With background motion, observers tend to perceive rigid figures that have a triangular shape. With figure motion, observers report seeing deforming figures with shapes that vary depending on the number of lines in the display. We consider two alternative accounts for this asymmetry which we term the background superiority effect (BSE). The first account proposes that the effect is due to retinal persistence and to figure stability. Against this line of explanation, we demonstrate that observers also see rigid triangular shapes in displays where both the figure and the radial lines rotate (double motion displays). The second account proposes that the effect depends on the availability of local kinematic information constraining contour orientation. This second line of explanation is consistent with observers' reports of bowed edges in double motion displays rotating in phase or in counterphase. Candidate mechanisms for extracting local kinematic information are discussed. PMID- 1745597 TI - Effects of chronic hypoxia and endurance training on muscle capillarity in rats. AB - Skeletal muscle capillarity expressed as capillary density (CD), and number of capillaries per fibre (C/F), as well as the mean fibre cross-sectional area (FCSA), were determined in the extensor digitorum longus (EDL), plantaris (PLA) and soleus (SOL) muscles of four groups of eight rodents trained on a swimming exercise programme (T) or maintained sedentary (S), at sea level (SL) or at simulated altitude (HA), barometric pressure 61.7 kPa (463 torr) for 12 weeks. It was shown that both HA exposure and endurance training decreased body and skeletal muscles weights (P less than 0.001). However, neither HA exposure nor endurance training induce any variation in relative importance in the skeletal muscle mass. Altitude exposure and endurance training had increasing effects on CD in all muscles studied (P less than 0.001). This study confirms the fact that altitude exposure has no direct effect on capillary development. On the other hand, the capillary supply of the several slow- and fast-twitch skeletal muscles studied is increased by endurance training. This real enhancement in capillary network is ascertained by an increase in the C/F ratio (+7%, +26%, +16%, in PLA, EDL, and SOL muscles, respectively at sea level, and +19.5%, +30%, and +14% respectively at HA). These results indicate that the effects of chronic exercise on skeletal muscle capillarity estimated by the C/F ratio, are greater in an hypobaric environment than in a SL environment. PMID- 1745598 TI - Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat. AB - The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle. PMID- 1745599 TI - Glomerular ultrafiltration in rabbits with superficial glomeruli. AB - The determinants of glomerular ultrafiltration in superficial glomeruli of a strain of English cross-breed rabbits have been studied using micropuncture techniques. Mean arterial blood pressure in the anaesthetised rabbits was 70 +/- 2 mmHg. The glomerular filtration rate in the kidney prepared for micropuncture was 4.4 +/- 0.4 ml/min, the filtration fraction was 22 +/- 1% and renal blood flow was 33 +/- 3 ml/min, and these values were comparable to values in conscious rabbits. Glomerular capillary pressure (Pgc) averaged 31 +/- 1 mmHg, the single nephron glomerular filtration rate (SNGFR) averaged 25 +/- 2 nl/min, and the mean ultrafiltration pressure (calculated using the whole-kidney filtration fraction) averaged 7 +/- 1 mmHg. A net positive pressure at the efferent end of the glomerular capillaries (4.4 +/- 0.9 mmHg) indicated that a state of filtration pressure disequilibrium existed, under the experimental conditions of this study, in rabbit glomeruli. The calculated glomerular ultrafiltration coefficient (Kf) was 0.08 +/- 0.01 nl s-1 mmHg-1. Thus, compared to the Munich-Wistar rat, SNGFR is lower in the rabbit. This reflects the substantially lower glomerular ultrafiltration pressure in the rabbit, although this was offset partially by a higher Kf. PMID- 1745600 TI - Glucose transporters do not serve as water channels in renal and intestinal epithelia. AB - Glucose carriers have been shown to serve as water channels in macrophages and in oocytes injected with messenger ribonucleic acid (mRNA) encoding the glucose carrier protein (Fischbarg et al. The contribution, therefore, of glucose carriers to osmotic water permeability (Pf) in renal and intestinal epithelial cells was investigated. Pf of brush border membrane vesicles (BBMVs) and of basolateral membrane vesicles (BLMVs) was studied using stopped-flow spectrophotometry. Osmotic shrinkage of renal vesicles exhibited fast and slow components at 4 degrees C and 37 degrees C. The fast component could be inhibited by HgCl2 or dimethylsulphoxide (DMSO) at these temperatures, whereas the slow component was inhibited only at 4 degrees C. Osmotic shrinkage of intestinal BBMVs and BLMVs was homogeneous at 4 degrees C and 37 degrees C and was slightly inhibitable by HgCl2 or DMSO at 4 degrees C but not 37 degrees C. In both tissues, vesicle uptake of glucose was sensitive to HgCl2, but not to DMSO. Phlorizin and phloretin inhibited D-glucose uptake in BBMVs and BLMVs respectively, but had no significant effect on Pf. In membrane vesicles of kidney origin, Pf was tenfold higher than in membranes from intestine. This difference was not reflected by the phlorizin- and phloretin-sensitive D-glucose uptakes. Our study concludes that glucose transporters do not serve as water channels in kidney or intestine. Although membrane proteins contribute slightly to Pf at 4 degrees C, this contribution is insignificant at 37 degrees C. A membrane protein serving specifically as a water channel could only be demonstrated in renal cortical membranes. PMID- 1745601 TI - Functional asymmetry of phosphate transport and its regulation in opossum kidney cells: phosphate "adaptation". AB - The polarity (apical vs basolateral cell surface) of the up-regulatory response ("adaptation") to low medium phosphate (Pi) concentration on apical and basolateral Pi transport systems was investigated in opossum kidney (OK) cell monolayers grown on permeant supports. Incubation of cultures in low-Pi medium, given either only to the apical or simultanously to the apical and basolateral compartments, increased the rate of transport of both the apical and the basolateral Na/Pi cotransport systems. The basolateral Na-independent, 4,4 diisothiocyanatostilbene-2,2'-disulphonic-acid-sensitive Pi transport system was unaffected by Pi deprivation. Incubation with low-Pi medium from only the basolateral side failed to elicit any "adaptive" response in Pi transport. When cells were Pi-limited either apically or on both sides for short periods of time, adaptation was apparent within 2 h and close to maximal by 6 h, and the alteration in Pi transport was consistant with an increase in Jmax for both the apical and basolateral Na/Pi cotransport systems. These data suggest that apical Na-dependent Pi influx is important in signalling the adaptive response to low extracellular Pi. PMID- 1745602 TI - Dihydropyridines interact with calcium-independent potassium currents in embryonic mammalian sensory neurons. AB - Early embryonic sensory neurons have two K currents resembling delayed rectifier and transient K currents of mature neurons. However, in contrast to those of adult neurons, the embryonic currents can hardly be separated either by electrophysiological or pharmacological methods, limiting their characterisation at these developmental stages. Using the whole-cell recording technique, we found that dihydropyridines (DHPs) inhibit the noninactivating component of the Ca independent K currents of 13-day mouse embryo dorsal-root ganglion (DRG) cells. The inhibitory effect of nicardipine began around 0.5 microM and was nearly complete at 5 microM while Na currents were not altered. This effect was reversible and voltage-dependent. The same results were obtained using another DHP Ca antagonist, nimodipine, whereas Bay K 8644, a DHP Ca agonist, had no effect. Kinetic properties of the DHP-insensitive K current have been described and compared with those of transient K currents found in differentiated neurons. These results suggest that both Ca and K channels have DHP sites, possibly homologous, at this developmental stage. The DHP inhibition of Ca-independent K channels provides a new tool with which to study K channels both at a molecular level and during DRG development. PMID- 1745603 TI - Postsynaptic inhibition by adenosine in hippocampal CA3 neurons: Co(2+)-sensitive activation of an inwardly rectifying K+ conductance. AB - The properties of the current underlying the membrane hyperpolarization evoked by adenosine (50-100 microM) were investigated in hippocampal CA3 neurons in vitro using current-clamp and single-electrode voltage-clamp techniques. In voltage clamp measurements, the adenosine-induced current (IAdo) was outward at rest and reversed at membrane potentials close to the equilibrium potential of K+ (EK), indicating that IAdo was carried by K+ ions. Determination of IAdo at several membrane potentials revealed a nonlinear current/voltage (I/V) relationship of the current displaying inward rectification in the hyperpolarizing direction. Similarly, adenosine increased the membrane slope conductance only at membrane potentials negative to rest, whereas the slope of the neuronal I/V curve remained unchanged when determined at potentials positive to rest. Since the electrophysiological properties of IAdo were very similar to those described for K+ conductances activated by other neuroactive substances like serotonin, opioid peptides and gamma-aminobutyric acid B receptor (GABAB) agonists, we conclude that IAdo belongs to a family of ligand-operated, inwardly rectifying K+ currents which apparently share a common mechanism to reduce postsynaptic excitability. As an additional feature, the postsynaptic adenosine response was reduced by bath application of Co2+ or Ni2+. The adenosine-induced membrane hyperpolarization was not affected by low-Ca2+ or low-Mg2+ solutions, nor by buffering of intracellular Ca2+, but a gradual decline of IAdo was observed following superfusion with Co2+ or Ni2+. In contrast, Mn2+ caused only a weak attenuation of the adenosine response. PMID- 1745604 TI - Effects of intracellular Ca2+ chelating compounds on inward currents caused by Ca2+ release from sarcoplasmic reticulum in guinea-pig atrial myocytes. AB - Ca2+ release from the sarcoplasmic reticulum (SR) of mammalian cardiac myocytes occurring either due to activation by a depolarization or the resulting transmembrane Ca2+ current (ICa), or spontaneously due to Ca2+ overload has been shown to cause inward current(s) at negative membrane potentials. In this study, the effects of different intracellular Ca2+ chelating compounds on ICa-evoked or spontaneous Ca(2+)-release-dependent inward currents were examined in dialysed atrial myocytes from hearts of adult guinea-pigs by means of whole-cell voltage clamp. As compared to dialysis with solutions containing only a low concentration of a high affinity ethylene glycol-bis(beta-aminoethylether) N,N,N',N' tetraacetic acid (EGTA) like chelator (50-200 microM), inward membrane currents (at -50 mV) due to evoked Ca2+ release, spontaneous Ca2+ release or Ca2+ overload following long-lasting depolarizations to very positive membrane potentials are prolonged if tne dialysing fluid contains a high concentration of a low affinity Ca2+ chelating compound such as citrate or free adenosine 5'-triphosphate (ATP). Without such a non-saturable Ca2+ chelator in the dialysing fluid, Ca(2+)-release dependent inward currents are often oscillatory and show an irregular amplitude. With a low affinity chelator in a non-saturable concentration, discrete inward currents with constant properties can be recorded. We conclude that the variability in Ca(2+)-release-dependent inward current seen in single cells arises from spatial inhomogeneities of intracellular Ca2+ concentration ([Ca2+]i) due to localized saturation of endogenous and exogenous high affinity Ca2+ buffers (e.g.). This can be avoided experimentally by addition of a non-saturable buffer to the intracellular solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745605 TI - Exercise-induced muscle damage in the rat: the effect of vitamin E deficiency. AB - Rats, fed a vitamin-E-deficient diet for 6 weeks, performed treadmill exercise for 2 h. Muscle damage was assessed by measuring the creatine kinase (CK) activity in plasma before and after exercise, and by studying semi-thin longitudinal sections of the soleus muscle 48 h after running. Vitamin-E deficient male and female rats showed an increased post-exercise CK activity when compared to matched controls, but male rats showed a larger CK response than females. This rise in plasma CK activity was caused mainly by an increased activity of the muscle-specific CK-isoenzyme, CK-MM (males + 1238%; females + 540%, P less than 0.05). In a parallel histological study we observed in vitamin E-deficient male rats a dramatic and significant disturbance of the normal cyto architecture of the muscle fibres after exercise (focal necrosis, phagocytosis and cellular infiltrates), whereas in females only minor, non-significant, changes were seen. We conclude that vitamin E deficiency enhances the susceptibility to exercise-induced muscle damage in male rats more than in female rats. This difference between the sexes is attributed to the protective effect of oestradiol that remains operative in female rats when the vitamin E status is disturbed: male rats lack such hormonal protection. PMID- 1745606 TI - Combined inhibitory actions of acidosis and phosphate on maximum force production in rat skinned cardiac muscle. AB - Possible interactions between the effects of pH and phosphate (Pi) on the maximum force development of cardiac myofibrils were investigated in rat skinned trabeculae in solutions of different pH (7.4-6.2) and [Pi] (where [] denote concentration). At pH 7.0 there was an inverse linear relationship between force and log [Pi] over the [Pi] range 0.2-20 mM; its slope (-0.46/decade) was twice that found previously for skeletal muscle [21]. Acidosis depressed force substantially, but the relative change of force was unaffected by Pi addition (0, 5, 20 mM); there was no evidence for the synergism between acidosis and Pi that would be expected if some of the inhibition by acidosis was due to protonation of Pi to the putative inhibitory form, H2PO4-. It was taken into account that even without Pi addition, there was enough Pi inside the muscle from various sources to produce significant changes in [H2PO4-] as the pH was varied. The results suggest that H+ and Pi inhibit maximum force development of cardiac myofibrils independently, by different mechanisms. From this it is argued that H+ and Pi may be released at different steps in the crossbridges cycle. In the myocardium Pi and H+ probably exert tonic inhibitory influences on cardiac myofibrils under all conditions. PMID- 1745607 TI - Adaptation of rat extensor digitorum longus to overload and increased activity. AB - Rat extensor digitorum longus (EDL) muscles were overloaded by removal of the synergist tibialis anterior (TA). The weight of the overloaded muscle was increased 15 days after the initial operation and remained higher throughout the period studied (153 days). The times to peak twitch tension and half relaxation remained unaltered, but the twitch and tetanic tensions developed by the overloaded EDL muscles increased. The overloaded EDL muscles became significantly more fatigue resistant. In a separate group of animals the overloaded EDL muscle was also chronically stimulated at 10 Hz. The additional stimulation altered the response of the EDL to overload in that the time to peak twitch tension of the muscle was slightly prolonged. There was no increase in twitch or tetanic tension in spite of the increase in muscle weight, but the electrical stimulation led to a further increase in fatigue resistance above that seen in overloaded muscles. The histochemical and immunocytochemical examination of the muscle revealed that there was a moderate increase in succinate dehydrogenase activity in the muscles overloaded only, but a considerable increase in those overloaded muscles that were also stimulated. There was no obvious change in the number of muscle fibres that reacted with an antibody to slow myosin in either overloaded only or overloaded and stimulated EDL muscles. Thus the addition of continuous activity to overload induced a slowing of contraction and prevented the increase of force usually induced by overload. PMID- 1745608 TI - Effects of Ca2+ removal and of tetraethylammonium on membrane currents induced by carbachol in isolated cells from the rat parotid gland. AB - In freshly dispersed rat parotid acinar cells, 10 microM carbachol increased outward currents at 0 mV and also inward currents at -70 mV recorded with the wholecell clamp method using patch pipettes containing 1 mM EGTA. When EGTA in the pipette was increased to 2.4 mM, carbachol increased only outward currents and a further increase of EGTA to 4 mM blocked the carbachol response. Effects of changes in external K+ and Cl- concentrations suggested that outward currents were carried by K+ and inward by Cl-. Effects of Ca2+ removal from the medium differed between experiments with 0 and 5 mM ATP in the patch pipettes. When pipettes contained no ATP, responses evoked by repeated applications of 10 microM carbachol (0.5-1 min) at 1.5-4 min intervals decreased only slowly after Ca2+ removal, outward currents being reduced to 90 +/- 6% and inward currents to 47 +/ 11% (n = 6) in 10 min. On the other hand, when 5 mM ATP was included in the electrodes, Ca2+ removal abolished the carbachol responses in about 5 min (n = 4). It was also found that tetraethylammonium (5 mM) strongly reduced both currents, by blocking muscarinic receptors, while Ba2+ (2.4 mM) inhibited only the outward K+ current. PMID- 1745609 TI - A simple method for monitoring changes in cell height using fluorescent microbeads and an Ussing-type chamber for the inverted microscope. AB - In this study, we report two developments for studies of ion transport in cultured epithelial cells. First, a convenient method is presented for measuring apparent cell height using fluorescent microbeads as high-contrast landmarks of the apical and basal cell surfaces. The apparent cell height is then used as an indicator to monitor the time course of changes in cell volume in response to osmotic perturbations. Second, an Ussing-type chamber design for the inverted fluorescence microscope is presented, which allows determination of transepithelial electrical properties. Using these two methods, we obtained simultaneous measurements of cell height and transepithelial electrical parameters for cultured renal (A6) epithelium. Cell height was measured by alternately focusing the microscope between microbeads marking the apical and basal surfaces. The distance between these two surfaces was measured electrically from the voltage output of a potentiometer that was mechanically coupled to the fine-focusing knob of the microscope. Following decreases in the bathing solution osmolality, the cell height and transepithelial Na+ transport rate (measured as short-circuit current, ISC) increased. The increase in cell height preceded changes in ISC by several minutes, suggesting a lack of direct linkage between changes in cell volume and transepithelial Na+ transport. Both the fluorescent microbead cell height method and the Ussing-type chamber can be used in conjunction with patch-clamp techniques, intracellular microelectrode impalements, or fluorescent probes of intracellular composition. Therefore, this system may be advantageous for studies of epithelial cell volume and channel regulation. PMID- 1745610 TI - Electrophysiological properties of membrane currents in single myometrial cells isolated from pregnant rats. AB - The whole-cell voltage-clamp method was applied to single smooth muscle cells prepared from the longitudinal layer of the pregnant rat myometrium (17-20 days of gestation). It was found that the transient inward current mainly consists of Ca2+ current, because the removal of Ca2+ ions from the external medium and 10 microM nifedipine eliminated this inward current. Its steady-state inactivation curve was obtained by the standard method, in which the membrane potential of half inactivation and the slope factor were estimated to be -58.0 +/- 4.9 mV (n = 11) and 8.9 +/- 1.4 mV (n = 11), respectively. In a small number of preparations (in 2 out of 30 preparations), there remained a very fast inward current in Ca(2+)-free medium containing Mg2+. Tetrodotoxin (TTX, 10 microM) can can abolish this current, suggesting that the channel for this current is equivalent to the Na+ channel in nerve cells. Two major phases of outward currents were identified by voltage jumps from negative holding levels to more positive levels. The first phase was a fast transient outward current. This current remained intact after external tetraethylammonium (TEA, 20 mM) was added. Following the transient current, a large delayed rectified outward current reached its peak over a period of 50 ms and then decayed. The reversal potential for this outward current was determined by observing the change of polarity of the tail currents with the change in extracellular K+ concentration [( K+]o). The slope for the change of reversal potential per ten-fold change in [K+]o is 57.7 mV at more than 23.2 mM [K+]o, indicating that this current is mostly carried by K+ ions. Voltage dependent inactivation of the delayed rectified outward current was determined by the standard method. The membrane potential for half inactivation and the slope factor were estimated to be -42.8 +/- 3.9 mV (n = 3) and 10.1 +/- 1.5 mV (n = 3), respectively. External TEA (20 mM) effectively eliminated the delayed rectified outward currents. Nifedipine (10 microM) suppressed not only Ca2+ current but also outward K+ currents. PMID- 1745611 TI - Influence of noradrenergic input into the hypothalamic paraventricular nucleus on fever in the guinea-pig. AB - The febrile response of guinea-pigs to a bacterial pyrogen was tested under different experimental conditions: (1) during electrical stimulation of the hypothalamic paraventricular nucleus (PVN), (2) after destruction of noradrenergic afferents into the PVN by 6-hydroxydopamine (6-OHDA), (3) during a microinfusion of noradrenaline (NA) into the PVN. Electrical stimulation of the PVN neurons by implanted microelectrodes reduced the febrile response to 45% of the control values. This confirmed the proposed antipyretic function of these neurons. Chronic destruction of noradrenergic afferents to the PVN by microinjected 6-OHDA also resulted in a significant reduction of febrile responses to 38% of the control values. A microinfusion of NA into the PVN enhanced the febrile responses to bacterial endotoxin by 39% in comparison to animals microinfused with the solvent (0.9% NaCl). Immunoreactivity to an antiserum against arginine vasopressin (AVP) was compared in PVN neurons of 6 OHDA-treated and of control animals. The number of AVP-immunoreactive perikarya and the intensity of immunoreactivity were increased in the animals treated with 6-OHDA, especially in the medial part of the PVN. Since fever was increased by microinfused NA and decreased by 6-OHDA treatment, we assume an inhibitory influence of noradrenergic brain stem afferents on the proposed antipyretic vasopressinergic system of the PVN. PMID- 1745612 TI - Monitoring exocytosis from single mast cells by fast voltammetry. AB - We have used fast differential ramp voltammetry with carbon-fibre electrodes to monitor exocytotic secretion in single rat mast cells. The oxidation peak and other aspects of the electrochemical profile of the substance released were similar to those of 5-hydroxytryptamine (5-HT) and the signals were increased by preloading the secretory granules with exogenous 5-HT. Metabolic blockade inhibited both visible degranulation and the electrochemical signal. For comparison, quinacrine, which is fluorescent and accumulates in secretory vesicles, was used as an alternative means of detecting secretion in single cells. The amplitude of the electrochemical signals observed during degranulation correlated well with the loss of quinacrine fluorescence. Both methods were used to record successive rounds of secretion in single mast cells in response to repeated applications of compound 48/80. PMID- 1745613 TI - Alkaline stress transforms Madin-Darby canine kidney cells. AB - Similar to growth factors aldosterone stimulates Na+/H+ exchange in renal target cells leading to cytoplasmic alkalinization. An alkaline intracellular pH reduces the H+ bonds between repressor proteins and DNA leading to the destabilization of the nuclear chromatin. We observed that sustained alkaline stress "per se" can lead to malignant transformation of Madin-Darby canine kidney (MDCK) cells. Cells grown for two weeks in alkaline culture medium (pH 7.8) developed multiple "foci" composed of spindle-shaped pleomorphic cells lacking contact inhibition and exhibiting poor adhesion to the culture support, typical characteristics of dedifferentiated tumor cells. "Focus" cells were cloned and grown in standard medium (pH 7.4). Cells maintained their abnormal growth pattern, indicating stable pH-induced genetic transformation. Cells were fused with polyethylene glycol to giant cells and impaled with microelectrodes. In contrast to non transformed giant MDCK cells the plasma membrane potential showed spontaneous oscillations that could be virtually abolished by the omission of extracellular Ca2+ or by the addition of the K+ channel blocker Ba2+. We conclude that sustained alkaline stress can induce malignant transformation in MDCK cells indicated by an abnormal growth pattern and by membrane potential oscillations most likely due to Ca2+ activated K+ channels in the plasma membrane. PMID- 1745614 TI - Inwardly rectifying currents in human term placental cells. AB - Using the whole cell voltage clamp technique, inwardly rectifying currents were observed in most cells isolated from human term placentas. Reversal potentials, estimated by extrapolation, as well as those estimated by tail currents, were found to be between -80mV and -90mV. These potentials are close to the potassium equilibrium potential (theoretical value: -82 mV). In addition, the inwardly rectifying currents were blocked by 1 mM CsCl. The elevation of [K]e increased the current amplitudes. Furthermore, the holding currents were inwardly shifted when the holding potential was kept at -70mV. The extrapolated reversal potentials changed linearly on a semilogarithmic graph with a slope of 57 mV/decade of [K]e. This value is close to the theoretical calculation (58 mV/decade). Consequently, it is suggested from these studies, that inwardly rectifying currents observed in human term placental cells are carried mainly by potassium ions. PMID- 1745615 TI - [Surgical tooth retention]. PMID- 1745616 TI - Management of drug interactions with cyclosporine. AB - Major advances in transplantation and in the treatment of autoimmune disorders have been achieved with the use of cyclosporine (CsA). During the past 10 years a variety of drug interactions have been reported to occur with CsA. These may be classified as either pharmacokinetic or pharmacodynamic in origin. Pharmacokinetic interactions are manifested by either an increase or decrease in the CsA concentration. The predominant mechanism of interaction is alteration in the cytochrome P-450 metabolism of CsA, however, some of the drugs may also affect its absorption, distribution, and elimination. Pharmacodynamic interactions include enhanced nephrotoxicity. Management of these events mandates proactive measures such as assessing the interactive potential of each new agent, measuring CsA concentrations more frequently when either initiating or discontinuing other agents, adjusting the dosage of CsA as necessary, and monitoring patients' clinical status to ensure efficacy and minimize the risk of toxicity. PMID- 1745617 TI - Complications associated with immunosuppressive therapy and their management. AB - Besides general complications of immunosuppression such as increased susceptibility to opportunistic infections or malignancy, individual immunosuppressive agents are associated with specific side effects. Nephrotoxicity is the major side effect of cyclosporine (CsA). Various attempts have been made to minimize this toxicity, such as monitoring drug blood levels, modifying the protocol, and coadministering other agents. Other side effects caused by CsA are hepatotoxicity, hyperkalemia, hypertension, tremor, gum overgrowth, and hirsutism. Azathioprine (AZA) causes dose-related bone marrow suppression, commonly leading to leukopenia. Careful monitoring of complete blood cell count and dosage adjustment according to white blood cell count are usually adequate to prevent serious leukopenia. The side effects of corticosteroids are numerous and include slow wound healing and de novo insulin-dependent diabetes mellitus. Many complications are dose related, and with low dosage or discontinuation of steroids, their frequency rapidly decreases. Antilymphoblast and antithymocyte globulins (P-ALG) are foreign antibodies and may cause allergic type reactions such as fever, chill, and hypotension. The initial side effect of monoclonal antibody (muromonab-CD3, OKT3) is similar to that of P-ALG. It includes high fever, shaking chills, headache, rigors, and hypotension. To prevent it, acetaminophen, an antihistamine, and a steroid usually are administered before injection. Because this agent is also associated with high frequency of pulmonary edema, it should not be given to any patient who has more than 3% body weight gain during the week prior to therapy. In rare case, it causes aseptic meningitis or encephalopathy, which is manifested by fever, severe headache, and seizure. PMID- 1745618 TI - Fixed-rate reimbursement fails to cover costs for patients with delayed graft function. AB - Medicare uses a fixed reimbursement schedule to pay the initial hospital costs for renal transplantation. This creates the potential to underpay for patients who develop the common complication of delayed graft function. We undertook a pilot study to determine if delayed graft function resulted in higher hospital charges and thus a loss in revenue when caring for these patients. Of 34 patients who experienced delayed graft function between October 12, 1987 and July 7, 1989, 9 (group 1) were randomly selected for study. During this same period 136 patients had immediate graft function; from them, another 9 (group 2) were selected by matching age, sex, and date of transplantation. The average (+/- SD) hospital stays for groups 1 and 2 were 17 +/- 8 and 10 +/- 2 days, respectively (p less than 0.001). The average time on dialysis for group 1 was 10.3 +/- 6.3 days (range 2-22 days). All dollars values were adjusted to a 1989 level, and we excluded kidney acquisition costs and professional fees. The average per patient charges for group 1 were $41,474 +/- 15,211 (range $21,926-$66,311), compared with $23,774 +/- 3245 (range $19,317-$29,702) for group 2 (p less than 0.001). We adjusted the charge values to estimate actual costs by using our hospital's average cost:charge ratio of 0.90 for 1987 and 1988, and 0.85 for 1989; the group 1 and group 2 average patient costs were $37,157 +/- 13,836 and $21,397 +/- 2921, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745619 TI - Recent advances in cyclosporine pharmacokinetics. AB - Although cyclosporine has been in clinical use for more than a decade, many questions persist concerning its pharmacokinetics. Gastric emptying, bile acids, and gastrointestinal motility can influence drug absorption after oral administration, but the relative importance of each of these factors and their interactions as determinants of absorption are not clear. The fraction unbound in plasma has been determined in several studies and may be associated with clinical effects. Biochemical and molecular studies have identified the specific cytochrome P-450 enzymes that metabolize cyclosporine to its primary metabolites. The drug's basic pharmacokinetic profile has been defined and many factors have been identified that can influence clearance, such as age, hepatic function, hematocrit, and lipoprotein concentrations. With the development of sensitive and specific analytical methods, many new cyclosporine metabolites have been identified in humans. The major metabolites are present in relatively high concentrations in human blood and have some immunosuppressive activity in vitro, but their contribution to in vivo immunosuppression is not clear. PMID- 1745620 TI - Analysis of cefepime tissue penetration into human appendix. AB - Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745621 TI - Pharmacokinetic evaluation of ethionamide suppositories. AB - The absorption and elimination of ethionamide (ETA) after oral tablets and rectal suppositories were determined in 12 healthy, adult male volunteers. A randomized, double-blind, double-dummy, crossover design was used. Treatments compared 250-mg ETA tablets and a placebo suppository to a 500-mg ETA suppository and two placebo tablets, given 7 days apart. Blood samples were collected at predetermined intervals for 12 hours after the dose. Serum concentrations of ETA were determined using high-performance liquid chromatography. The area under the serum concentration-time curve was used to compare the relative bioavailability of ETA from the two preparations. Relative bioavailability after rectal administration was 57.3% of that after oral administration. The maximum serum concentration after rectal administration was 33% of that after oral administration. Higher doses of ETA and serum concentration monitoring are recommended whenever the suppositories are used. PMID- 1745622 TI - Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain. AB - Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model. PMID- 1745623 TI - Effects of acetaminophen after bilateral oral surgery: double dose twice daily versus standard dose four times daily. AB - We compared acetaminophen (APAP) double dose 2000 mg twice a day on the day of oral surgery, decreasing to 1000 mg twice a day for the next 2 days, to a standard dose 1000 mg 4 times a day then 500 mg 4 times a day for 2 days. Compared to the double dose, there was 19% (p = 0.03) less edema after the standard regimen on the third postoperative day. No statistical difference was seen between the two treatments with respect to ability to open the mouth, temperature on the nonoperated versus operated side, or summary analgesic efficacy measures. However, pain intensity scores indicate that APAP double dose gave less analgesia toward the end of the dosing interval than the standard regimen. It is proposed that double-dose APAP twice daily does not have any analgesic and antiedematous advantages over the standard dose 4 times a day. The analgesic and antiphlogistic efficacies of APAP apparently do not coincide. PMID- 1745624 TI - Ampicillin-sulbactam and ticarcillin-clavulanic acid: a comparison of their in vitro activity and review of their clinical efficacy. AB - Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the beta lactamases in the Richmond and Sykes classes II-VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some beta-lactamase-producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I beta-lactamases frequently produced by Pseudomonas aeruginosa, Enterobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies. PMID- 1745625 TI - Fatal hepatotoxicity induced by hydralazine or labetalol. AB - Antihypertensive agents have been associated with adverse reactions that, if unrecognized by health practitioners, may have devastating consequences. The pattern of hepatotoxicity observed during therapy with the vasodilator hydralazine is highly variable, often making its diagnosis difficult. Serious hepatic injury induced by the alpha- and beta-adrenergic receptor antagonist labetalol has only recently been reported and therefore, many clinicians may be unaware of this adverse effect. Familiarity with the clinical features and course of hydralazine- and labetalol-induced hepatic injury is necessary to ensure prompt recognition and discontinuation of the agent. PMID- 1745626 TI - Eosinophilic pustular folliculitis (Ofuji disease) in childhood: a review of four cases. AB - Four children under 2 years of age were treated at our hospital in the last three years with a recurrent vesiculopustular eruption of the scalp, variably extending to the face and limbs. All cases followed a cyclical pattern. Three of the children had a moderate response to topical steroids, and one went into remission after a two-month course of erythromycin. Ethnic origin may be an important predisposing factor. Histologically, all patients showed a moderate mixed inflammatory infiltrate with numerous eosinophils centered around hair follicles. Peripheral white blood cell count showing leukocytosis with eosinophilia was observed in those cases measured, but no consistent immunologic abnormalities could be identified. PMID- 1745627 TI - Cutaneous and oral lesions in 32 children after renal transplantation. AB - A variety of skin and oral mucosal lesions appearing in patients after renal transplantation have been reported in the literature. Because most of these data pertain to adults, we studied a group of children with kidney transplants to investigate the occurrence of skin and/or oral mucosal lesions, compare them with those observed in adults, and contribute to the knowledge of the pathogenesis of these disorders. Our series consisted of 32 patients aged 5 to 18 years, all of whom had skin and/or oral mucosal lesions that were classified as being either drug induced, probably related to uremia, or due to other causes. A possible relationship between drug-induced lesions and the therapeutic immunosuppressive regimen in use was investigated. In addition, two formerly unreported lesions were seen in these patients: hypertrophy of lingual fungiform papillae and onychoschizia. The former occurred only in children receiving cyclosporine. Compared with adults, the frequency of gingival hypertrophy was higher and that of infectious disease was lower. PMID- 1745628 TI - Progressive early dermatologic changes in Hutchinson-Gilford progeria syndrome. AB - We describe evolving dermatologic findings in a male with progeria from age 1 month to 21.5 months. At 18 months of age, irregular pigmentary changes of the abdomen, early occipital alopecia, superficial scalp veins, glyphic nasal tip, absent ear lobules, coarse hair that stands on end, crowded dentition with delayed tooth development, and dystrophic nails permitted the diagnosis of progeria. Radiographs showed evidence of resorption of the distal ends of the clavicles, attenuation of the terminal phalanges, diffuse osteopenia, and fishmouth vertebral bodies, which are typical of this syndrome. Appreciation of the evolution of early dermatologic findings may permit earlier diagnosis of this condition in infants with skin changes. PMID- 1745629 TI - Spray-induced frostbite in a child: a new hazard with novel aerosol propellants. AB - A case of deep frostbite occurred in an 8.5-year-old child. The lesion was due to the improper use of a toilet air freshener and was severe enough to require a skin graft. The propellants contained in the spray were propane and butane. We measured the temperature of this aerosol during spraying (-40 degrees) in comparison with an ethyl chloride spray (-3 degrees) widely used for local skin anesthesia. This difference is mainly due to the much lower evaporation temperature of propane (-42.2 degrees) and butane (-0.6 degrees) compared with ethyl chloride (12.5 degrees). This child aimed the spray directly toward his skin, thus producing a deep frostbite. We wish to draw the attention of clinicians to this potential hazard with new propellants, since they should soon replace chlorohydrofluorocarbons throughout the world for ecologic reasons. PMID- 1745630 TI - Subcutaneous fat necrosis in two infants after hypothermic cardiac surgery. AB - Two infants experienced subcutaneous fat necrosis (SCFN) at a relatively late age after cardiac surgery with induced hypothermia. The condition resolved in both patients over four weeks without treatment. The appearance of SCFN after the newborn period is very unusual, and in these patients was probably related to the hypothermia. PMID- 1745631 TI - Langerhans cell histiocytosis masquerading as lichen aureus. AB - We report a 13-year-old boy with localized Langerhans cell histiocytosis. The lesion was restricted to the skin of the mons pubis and clinically resembled lichen aureus. Histopathologic and electron microscopic examinations of a skin biopsy specimen of the lesion showed typical features of Langerhans cell histiocytosis. Extensive examination revealed no other organ involvement. PMID- 1745632 TI - Juvenile pemphigus vulgaris: efficacy of moderate doses of deflazacort. AB - A 13-year-old girl with pemphigus vulgaris (PV) had clinical features of chronic stomatitis. The histologic and immunologic findings were typical of a diagnosis of PV. Good therapeutic results were obtained with moderate doses of deflazacort, 1 mg/kg/day slowly tapered to 0.1 mg/kg every other day. The patient had no significant side effects. PMID- 1745633 TI - Papular acrodermatitis of childhood (Gianotti-Crosti disease). AB - An 11-year-old boy had lentil-sized lichenoid papules, localized to the limbs and trunk, together with acute, nonicteric, hepatitis B surface antigen-positive hepatitis. The clinical picture and course were typical of Gianotti-Crosti disease. Monoclonal antibodies were used to study the lymphocyte subpopulations and surface antigens in the inflammatory infiltrate in frozen sections of a skin biopsy specimen. The results provide data on the pathogenic mechanism of the papular exanthem. PMID- 1745634 TI - Discrete pigmentation after chemotherapy. AB - Discrete areas of cutaneous hyperpigmentation were seen in two children with metastatic sarcoma who received chemotherapeutic bone marrow ablation with cyclophosphamide, etoposide, and carboplatin prior to autologous bone marrow transplantation. The hyperpigmented patches occurred only in areas of skin occluded by tape, electrocardiogram pads, or elastic bandages. Identical skin findings were reported in five adult women who received intravenous thiotepa and cyclophosphamide. Measurable levels of thiotepa were detected in these patients' serum, skin, sweat, and occluded gauze, suggesting that the chemical was excreted onto the skin surface in sweat and accumulated under occlusive dressing, thus producing some toxic effect on the epidermis or melanocytes resulting in abnormal pigmentation. We suspect that a similar mechanism was operative in our patients to produce the unusual patterned hyperpigmentation, and suggest that this complication may be prevented by minimizing sweat accumulation in areas occluded by adhesive materials. PMID- 1745635 TI - Oral acyclovir therapy for varicella and zoster infections in pediatric and pregnant patients: a brief review. AB - Oral acyclovir recently was approved for the treatment of herpes zoster and has been shown to be effective in the treatment of varicella. Studies of the use of high-dose oral acyclovir in the management of varicella-zoster infections in immunocompetent pediatric patients are reviewed. Guidelines are provided for the drug's use in immunocompetent children and adolescents, pregnant patients, and pediatric atopic patients receiving systemic steroids. PMID- 1745636 TI - Scissor excision plus electrocautery of anogenital warts in prepubertal children. AB - Nineteen prepubertal children with anogenital (AG) warts were treated by scissor excision plus electrocautery under general anesthesia. Median posttreatment follow up was nine months. Minor clinical recurrences were seen in five (26.3%) children, all within three months after treatment. Recurring warts responded in all cases to home application of 0.5% podophyllotoxin (Condyline). Surgery plus electrocautery was well tolerated with no notable side effects. It is simple, safe, and efficacious, and is a suitable second-line treatment for AG warts in children. PMID- 1745637 TI - Wiskott-Aldrich syndrome. PMID- 1745638 TI - Multiple cutaneous ulcers in a premature neonate. PMID- 1745639 TI - Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. PMID- 1745640 TI - Pulmonary veins in total anomalous pulmonary venous connection with obstruction: demonstration using silicone rubber casts. AB - We studied the postmortem vascular anatomy of four patients with total anomalous pulmonary venous connection (TAPVC) with obstruction using a silicone rubber casting method. Two patients were studied clinically but died before therapeutic intervention, one died after corrective surgery, and another was not diagnosed before death. The morphologic types were supracardiac (2), infracardiac (1), and mixed (1). One of the supracardiac forms had a stenosis at the left vertical vein by a bronchoarterial vise, and a collateral channel to the right superior caval vein was also present. In the other supracardiac case, a left upper pulmonary vein was connected to the left vertical vein above the stenotic portion, resulting in postoperative pulmonary hemorrhage into the left upper lobe. The patient with infracardiac TAPVC had a tree-shaped descending vertical vein and small opening at the inferior caval vein. In the mixed type, a right upper pulmonary vein ran between the pulmonary artery and bronchus draining into the superior caval vein, and the rest of the drainage was to the portal vein. PMID- 1745641 TI - Anomalies of the brain and congenital heart disease: a study of 52 necropsy cases. AB - During routine autopsy examinations several macroscopic anomalies of brains were noted in children with congenital heart disease (CHD). To define these observations 52 autopsies of cases with CHD as well as 52 controls were compiled. Cases were divided into two groups according to the absence (group I) or presence (group II) of a multimalformative syndrome (MMS). Fifty percent of the sample was associated with MMS. Brain anomalies were classified into grades I, mild and focal; II, intermediate, focal or diffuse; and III, severe and diffuse. Group I was associated with brain anomalies (mainly of grades I and II with altered gyri) in 19 of 28, whereas in Group II the brains frequently had compromise of lobes, gyri, and fissures, 18 of 24. The relationship between the types of CHD, grade of brain anomalies, and MMS is delineated. The high frequency of brain anomalies associated with CHD but without other malformations (67.8%) suggests a clinical counterpart of these lesions. PMID- 1745642 TI - Sudden death in an infant with central nervous system abnormalities. AB - Some deaths during the first year of life are classified as sudden infant death syndrome (SIDS), the diagnosis of which requires a complete autopsy without adequate explanation for the death. We report a 1-month-old infant whose clinical history was fairly typical for SIDS. Postmortem examination was remarkable in revealing clinically unsuspected central nervous system (CNS) abnormalities, including lobar holoprosencephaly, absence of the olfactory tracts and grooves (arhinencephaly), subependymal gray matter heterotopias, and delayed myelination. Although the CNS findings do not adequately explain the patient's sudden death, this case illustrates the need for a complete autopsy to include careful CNS evaluation, especially in any presumed SIDS death. PMID- 1745643 TI - Cortical dysgenesis in a variant of phenylketonuria (dihydropteridine reductase deficiency). AB - The neuropathology of a 2 1/2-year-old patient with dihydropteridine reductase deficiency showed diffuse demyelination throughout white matter and spongy vacuolation in the long tracts of the brain stem. These changes are characteristic neuropathologic observations in untreated phenylketonuria. In addition, extensive neuronal loss, calcification and abnormal vascular proliferation were noted in the cerebral cortex, white matter, basal ganglia, and thalamus. Golgi studies demonstrated an abnormal orientation of neurons together with abnormalities of dendrites and dendritic spines. The pathogenesis of the vascular abnormalities in this condition is unknown, although folate deficiency may be involved. The secondary deficiency of serotonin and dopamine occurring during neuronal growth and differentiation may also affect the terminal stages of neuronal maturation. PMID- 1745644 TI - A historical view: diethylstilbestrol use during pregnancy: a 30-year historical perspective. PMID- 1745645 TI - Arteriopathy in children with AIDS: microscopic changes in the vasa vasorum with gross irregularities of the aortic intima. PMID- 1745646 TI - [The effect of various culture parameters on the yield of restriction endonuclease Sfa NI]. AB - A simple technique is proposed for testing the restriction endonuclease Sfa NI activity in lysates of Streptococcus faecalis cells. The technique was used to study the effect of inorganic phosphate and the growth phase on the enzyme yield. Conditions were chosen that provide a high yield of the Sfa NI activity and a significantly reduced level of nucleases in the cells. PMID- 1745647 TI - [Adsorption immobilization of alkaline lipase]. AB - A polyamide with the covalently coupled phosphatidyl ethanolamine was used for affinity adsorption of an alkaline lipase from Pseudomonas aeruginosa. The immobilization resulted in increase of the enzyme specific activity. Some properties of native and adsorbed enzyme were compared. The temperature optima, heat and pH stability, KM and Vmax values were determined for both native and immobilized enzymes. PMID- 1745648 TI - [Various lipases for producing products enriched with polyenic acids in fish fat hydrolysis]. AB - The enzymic hydrolysis of fish with lipases from various sources was studied. The lipase from the fungus Rhizopus microsporus preferentially removes saturated fatty acids, while lipase from the pyloric caeca of salmon unsaturated fatty acids upon hydrolysis of fish fats. The enzymes can be used to obtain fatty products enriched with eicosanopentaenoic acid, mono- and diacylglycerols by enzymic hydrolysis of the ivasi fat. PMID- 1745649 TI - [Role of the energy status of Escherichia coli in cell membrane phospholipid composition changes during aerobic-anaerobic transitions]. AB - The aerobic to anaerobic transition of E. coli is accompanied with interrelated changes of the adenylate pool, energy charge, respiration rate, as well as the phospholipid content of the cell membranes and the activity of the polyamine synthesizing system. The role of the cellular energy status in the control of the relative content of membrane phospholipids is discussed. The control is based either on energy redistribution in phospholipid metabolism or on the effect on the activity of the polyamine synthesizing system. PMID- 1745650 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1745651 TI - The effect of adjuvant-induced arthritis on rat leukocyte membrane phospholipid fatty acid levels following fish oil feeding. AB - Inflamed rats with adjuvant-induced polyarthritis showed similar incorporation of dietary eicosapentaenoic acid (EPA) into peritoneal exudate cell (PEC) membrane phospholipids compared to pair fed non-inflamed control rats. Arachidonic acid (AA) content was similar in PEC phospholipids of inflamed and control rats whereas the linoleic acid content was consistently higher in inflamed rats. PMID- 1745652 TI - Blood pressure reduction by fish oil in adult rats with established hypertension- dependence on sodium intake. AB - The effects of fish oil combined with dietary sodium restriction on blood pressure and mesenteric vascular resistance were examined in a series of experiments with adult normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed normal or low sodium diets containing fish oil, olive oil or safflower oil. Small but significant reductions of blood pressure (measured directly in conscious rats) were seen in SHRSP but not in WKY after 8 weeks on a fish oil/low sodium diet, compared with rats fed olive or safflower oil diets with normal sodium content. This antihypertensive effect was not dependent on neurally mediated vasoconstriction but was associated with a reduction of basal resistance in the blood-perfused mesenteric artery. Subcutaneous injection of fish oil reduced blood pressure in adult SHRSP on a normal sodium diet. However, there was a further fall in blood pressure when sodium intake was reduced. The results indicate the antihypertensive effect of fish oil can be enhanced by restricting sodium intake. PMID- 1745653 TI - Dietary fish oil administration retards the development of hypertension and influences vascular neuroeffector function in the stroke prone spontaneously hypertensive rat (SHRSP). AB - An influence of fish oils (rich in eicosapentaenoic acid, EPA) in modulating (a) the development of hypertension in the stroke prone spontaneously hypertensive rat (SHRSP) and (b) vascular neuroeffector mechanisms in the SHRSP was explored. Rats (SHRSP) were placed on a series of diets for a period of 13 weeks from 4 weeks of age. The fatty acid composition of the diets was derived from fish oil, olive oil, safflower oil or beef fat. After 13 weeks, rats fed diets containing fish oil (at a total dietary fat level of either 5% or 15%) had mean blood pressures approximately 20-25 mmHg lower than other SHRSP rats maintained on diets containing either olive oil, safflower oil or beef fat. The dietary schedules providing fish oil depressed the contractile responses mediated by sympathetic nerve stimulation in the mesenteric vascular bed preparation. The results suggest that the n-3 polyunsaturated fatty acids retard the development of hypertension in the SHRSP rat and modulate the contractile responses of blood vessels mediated by sympathetic nerves in the isolated perfused mesenteric vascular bed preparation. PMID- 1745654 TI - Interactions between n-3 and n-6 essential fatty acids (EFAs) in the regulation of cardiovascular disorders and inflammation. AB - Much attention has recently been paid to the possible benefits of increasing the intake of eicosapentaenoic acid (EPA) by consuming fish oil. However, this can have adverse effects such as raising cholesterol levels in patients with hyperlipidaemia and causing a deterioration in glucose tolerance. High doses of EPA given to Westerners also lower levels of dihomogammalinolenic acid (DGLA), a substance with a wide range of desirable cardiovascular and antiinflammatory actions. This lowering of DGLA does not occur in Eskimos who consume large amounts of EPA, indicating that there may be differences in essential fatty acid metabolism between Westerners and Eskimos. Therapeutic strategies are required which raise both EPA and DGLA and which do not raise EPA at the cost of lowering DGLA. PMID- 1745655 TI - Release and effects of prostaglandins in ocular tissues. PMID- 1745656 TI - Inhibition of PGE2 production in macrophages from vitamin E-treated rats. AB - Rat peritoneal macrophages from vitamin E-treated rats (5 mg per rat for 6 successive days) contained 403.3 +/- 90.7 ng alpha-tocopherol/10(6) cells, whereas control macrophages contained 1.2 +/- 0.4 ng. PGE2 production in the macrophages from vitamin E-treated rats was significantly suppressed when stimulated with PMA and calcium ionophore A23187. The mechanism of vitamin E inhibition of PGE2 production in macrophages was investigated. The release of (14C)-arachidonic acid from pre-labeled macrophages and the conversion of (14C) arachidonic acid to PGE2 by the homogenate of the cells were remarkably reduced. These results strongly suggested that the inhibition of PGE2 production by vitamin E results from the inhibition of the activities of both phospholipase A2 and cyclooxygenase. PMID- 1745657 TI - Influence of dietary fatty acids on phospholipid composition and prostaglandin E synthesis in rat kidneys. AB - The effects of oils with different amounts of n6 and n3 fatty acid precursors and derivatives were evaluated on phospholipid composition and PGE2 synthesis of rat kidneys. Dietary lipids were: olive oil, an olive-blackcurrant-fish oil mixture and a blackcurrant-fish oil mixture. We observed in the kidneys of rats fed the blackcurrant-fish oil mixture a significant decrease in PGE2 synthesis, while arachidonate values did not show significant variations. A decrease of PGE2 synthesis could be due to competitive and inhibitory effects of fatty acids other than arachidonate, observed in the kidney phospholipid composition in our dietary conditions. PMID- 1745658 TI - Dietary factors in the fall in coronary heart disease mortality. AB - The role of dietary change in the fall in heart disease mortality has been hotly debated. Three countries, Australia, USA and UK with equal 'care' and sophistication of surgical techniques have shown different timing in the beginning of the decline of this 'epidemic'; around the mid 1960s in the first two countries, but not until the late 1970s for the UK. The cause of this difference may be the changing food habits of their populations. Using food disappearance data, apparent consumption of butter and margarine show opposite trends (butter down and margarine up) predating the decline in mortality in both the USA and Australia by at least 7 years and also in the UK, but at a later time, (about 1970). Changes in adipose tissue linoleate, a marker for polyunsaturated fat intake, support this indirect evidence, with depot levels rising in the USA from the 1960s and 10 years later in the UK. Other evidence support the view of decreasing saturated fat intake and increasing polyunsaturated intake prior to 1960 in the USA. Although many factors must contribute to the decline in mortality from CHD, change in dietary P/S ratio would seem to be the major dietary contributor. PMID- 1745659 TI - Neural network modelling. PMID- 1745660 TI - The use of narrowband ultrasound for characterization of tissue in a thin layer. AB - Most tissue characterization methods use RF data originating from backscattering processes in the insonified tissue. Characterization of the tissue of a thin layer (e.g., an artery wall) poses problems because of the small amount of data available. The tissue layer may be so thin that there are no RF data that are not corrupted by the reflections from nearby interfaces. An alternative approach may be to compare the spectra of the reflections at the boundaries of the layer for the characterization of the tissue in between. To avoid problems that arise from the use of short (broadband) pulses the method proposed here uses long and almost monochromatic pulses. The frequency dependence of the acoustic parameters can be assessed by using different central emission frequencies. A deconvolution algorithm is used to separate overlapping reflections from closely spaced tissue interfaces. Wiener inverse filtering together with correlation of deconvolved signals results in an accurate determination of the position of specular reflectors. The accuracy of the peak values detected in the envelope signal is not sufficient for quantitative determination of tissue parameters, but still much better than results from the analysis of short waveforms. PMID- 1745661 TI - The interaction of ultrasound with cancellous bone. AB - The Biot theory is used in an attempt to explain the frequency dependence of ultrasonic attenuation, f(alpha), in cancellous bone. Measurements of f(alpha) in samples of cancellous bone are compared with values calculated using parameters established from bone samples by statistical histomorphometry. Ultrasonic attenuation in cancellous bone correlates with trabecular bone volume but the Biot theory, although producing qualitative agreement produces quantitative results which are significantly deviant using parameters presently available. At the present time, too many of the Biot parameters are insufficiently defined for cancellous bone, to allow a complete test of the model. PMID- 1745662 TI - Treatment planning optimization using constrained simulated annealing. AB - A variation of simulated annealing optimization called 'constrained simulated annealing' is used with a simple annealing schedule to optimize beam weights and angles in radiation therapy treatment planning. Constrained simulated annealing is demonstrated using two contrasting objective functions which incorporate both biological response and dose-volume considerations. The first objective function maximizes the probability of a complication-free treatment (PCFT) by minimizing the normal tissue complications subject to the constraint that the entire target volume receives a prescribed minimum turmourcidal dose with a specified dose homogeneity. Probabilities of normal tissue complication are based on published normal tissue complication probability functions and computed from dose-volume histograms. The second objective function maximizes the isocentre dose subject to a set of customized normal tissue dose-volume and target volume dose homogeneity constraints (MVDL). Although the PCFT objective function gives consistently lower estimates of normal tissue complication probabilities, the ability to specify individualized dose-volume limits, and therefore the individualized probability of complication, for an individual organ makes the MDVL objective function more useful for treatment planning. PMID- 1745663 TI - A total body nitrogen facility for paediatric use. AB - The design, calibration and evaluation of a facility for in vivo prompt gamma neutron capture analysis of total body nitrogen in children is described. The patient is scanned in both supine and prone positions, across a vertically collimated beam from a 1 GBq 252Cf fission source. Two NaI(T1) detectors are placed on either side of the patient, perpendicular to both the neutron beam and the scanning direction. The effective dose equivalent delivered to a child during an 840 s scan is approximately 0.14 mSv (QF = 10). Correction factors for nitrogen background (width-dependent), hydrogen background (1-4% of hydrogen gamma ray peak) and the differential attenuation of nitrogen and hydrogen gamma rays (width-dependent) can be applied to the measured nitrogen-to-hydrogen gamma ray counts ratio. By using the mass of hydrogen (based on body mass and fat mass) as an internal standard, the nitrogen mass can then be determined. Measurements with a urea-containing box phantom show that the current precision (CV) of the net nitrogen counts and of the nitrogen-to-hydrogen counts ratio is +/- 2.0% and +/- 1.5%, respectively. Using small anthropomorphic and other phantoms, estimation of the mass of nitrogen has a precision of +/- 1.4 to 5.4% and an accuracy of 97.1 to 101.5%. PMID- 1745664 TI - X-ray computed tomographic (CT) phantom designed for the development of techniques for measurement of myocardial perfusion. PMID- 1745665 TI - An articulatory study of consonant-induced vowel duration changes in English. AB - The effects of voicing, manner, and number of consonants on the duration of previous vowels in English can be created in three ways: by planned expansion or contraction of the entire vowel, by changing the relative timing of consonant and vowel gestures, or by modifying the duration of the closing movement for the consonants. An X-ray microbeam data base of 2 speakers of American English reciting monosyllabic words, which differed in their final consonants and in their position in the accentual structure of the utterance, was studied to evaluate these three accounts. In this data base, vowel duration differences due to the voicing of the following consonants were amplified by the presence of accent. Also, many of the duration differences associated with the following consonants are localized in the later portion of the opening movement, suggesting that subjects often create vowel duration changes by initiating the consonant closing gesture at an earlier or later time relative to the opening gesture. PMID- 1745666 TI - The representation of stop consonants in three-dimensional acoustic space. AB - An acoustic study of English initial voiced stops showed that the three place categories are well distinguished on the basis of three properties: second formant onset frequency (F2 onset), second-formant frequency of the vowel nucleus (F2), and third-formant onset frequency (F3 onset). Ten male and 10 female subjects produced multiple tokens of /bVt/, /dVt/, and /gVt/ with ten different medial vowels. Three-dimensional scatterplots were generated using the above acoustic properties as coordinates. Three nonoverlapping clusters corresponding to the three place categories were evident across all subjects. Discriminant analyses based on F2 onset, F2 vowel, and F3 onset as predictor variables showed a mean correct categorization rate of 84.5% when tested within gender groups. The graphic and statistical results are interpreted as indicating that phonetic categories may be defined and represented in purely acoustic terms if variably valued multiple acoustic properties are relationally examined. PMID- 1745667 TI - The stop/glide boundary shift: modelling perceptual data. AB - Research in speech perception has suggested that listeners often adjust category boundary locations for differing contexts. The stop/glide (e.g.,/ba/vs./wa/) boundary shift occurring with changes in syllable duration has been interpreted as reflecting 'rate normalization' by some, whereas others have suggested an auditory basis for the shift. Clarification of both the causes and the effects of the stop/glide shift is being sought through experimentation intended to expand our knowledge of variations in the shift across different experimental treatments. The present study extends research on the stop/glide shift by (1) showing that the shift is not an artifact of a particular stimulus pattern that had been present in all the previous studies of the effect, (2) further demonstrating the nonlinear character of the identification shift, (3) providing additional evidence of the role of presentation format (mixed vs. blocked) in the identification shift, and (4) exploring boundary locations in various discrimination paradigms. The complex outcomes of the studies reported here as well as a variety of previous results are interpreted as compatible with expanded versions of the durational contrast hypothesis. Two versions are considered, one in which the shift is seen as due to a mechanism of contrastive perception that applies to events of comparable duration, and one in which the shift is seen as a perceptual error that occurs when the auditory system attempts to track frequency trajectories that change (i.e., pivot) over time. PMID- 1745668 TI - Neurological correlates of unilateral and bilateral "strokes" of the middle cerebral artery in the rat. AB - Rats with unilateral lesions of the middle cerebral artery (MCA) were tested for the ability to detect (touch) and remove a square of adhesive tape from each forepaw, and for performance on a number of neurological tests (e.g., placing and hopping reflexes, activity). Rats with MCA damage showed deficits in both touching and removing the tape from the paw contralateral to the damage, but not ipsilateral to the damage, while performing within normal limits on the other tests. After scores of the MCA rats dropped into the control group range on the adhesive tape test, they sustained damage to the opposite MCA. This did not reinstate the original deficit, suggesting that the recovery seen after the unilateral lesion was not mediated by the opposite cortex. The second lesion, however, caused a deficit in removing the adhesive tape from the limb opposite the new stroke. Some of the rats that originally had sham operations received bilateral MCA lesions at this time. These animals showed much more severe deficits on the adhesive tape test than the rats with sequential strokes. Rats with bilateral MCA damage (simultaneous or sequential) also slipped on a long narrow plank more often than control animals. Nimodipine did not enhance recovery on any of the behavioral measures. PMID- 1745669 TI - Sociophysiology of relationships in squirrel monkeys. I. Formation of female dyads. AB - Physiological and behavioral consequences of formation of female-female relationships were investigated in adult squirrel monkeys. Plasma cortisol, heart rate, and behavior were evaluated during confinement in a test cage while animals were housed alone, during the first hour of isosexual pair formation, and while animals were housed as isosexual dyads. In addition, basal cortisol levels were assessed both before and after pair formation, as were behavioral and cardiovascular responses to social and nonsocial stimulus presentations. Basal cortisol levels underwent a marked and sustained reduction following formation of pairs, independent of both dominance status and the quality of social interactions between pairmates. In contrast, adrenocortical responsiveness was not altered by social conditions, apart from a modest and transitory difference between dominant and subordinate females in their initial response to pair formation. Heart rate declined sharply during each test session, but did not reliably differentiate social conditions, stimulus conditions, or dominance status. These findings contrast with results of a parallel study of male squirrel monkeys and suggest that isosexual relationships in males and females are associated with different sociophysiological processes. PMID- 1745670 TI - Brood patch innervation and its role in the onset of incubation in the turkey hen. AB - The source of innervation to the brood patch in turkey hens was determined by recording the electrophysiological activity of cutaneous nerves while manually stimulating various regions of the skin. The entire area of the brood patch was innervated by eight nerves, arising from thoracic vertebra 3 to synsacrothoracic vertebra 1. To determine whether afferent input from the brood patch influenced egg production or incubation behavior, hens were bilaterally denervated prior to photoinduced egg production. Denervated hens visited nests the same number of times, but stayed on the nest for less total time than controls by the fourth week of photostimulation. Serum prolactin levels rose in control hens but not in denervated hens. Egg production was maintained in the denervated hens but not in controls. None of the denervated hens displayed incubation behavior. This experiment supports the view that peripheral nervous input plays a role in the onset of incubation behavior. PMID- 1745671 TI - Individual variation in the neural timing of infanticide and parental behavior in male house mice. AB - In male house mice (Mus domesticus and M. musculus), the act of coital ejaculation provides a fail-safe neural signal for timing the birth of their offspring. A unique aspect of this phenomenon is the extraordinary latency that can occur between the stimulus (ejaculation) and its adaptive neural response (male mice cease killing pups and behave parentally toward them). Thus the inhibition of infanticide is routinely time-delayed for many days after mating. In the absence of mating, cohabitation with a female will not inhibit infanticide in CF-1 stock males (M. domesticus), whereas the birth of pups in the male's home cage will inhibit infanticide. But with regard to the ejaculatory phenomenon, which also includes the spontaneous reemergence of infanticide 50-60 days after mating, this entire behavioral cycle toward pups can occur in the total absence of regular time cues from a light/dark cycle following ejaculation. However, exposure to photoperiodic (L:D 12:12) or constant light (LL) accelerated the transition time from infanticide to parenting after ejaculation, while in constant dark (DD), the transition time to parenting was significantly prolonged. The time interval between ejaculation and the inhibition of infanticide, which varied among individuals first mated at 6 months of age, was repeatable when the same males were remated at 9 months of age; however, when males were again mated at 18 months of age, the time interval between ejaculation and parenting was dramatically prolonged. In general, coital ejaculation triggers a neural timing system that cannot be explained by any presently known physiological mechanism. Our results do suggest, however, that the neural timing variation observed among individuals is influenced by sex steroid exposure during late fetal development. PMID- 1745672 TI - Effect of dietary protein and environmental factors on lactation performance in rats. AB - The effects of dietary protein and environmental conditions on lactation performance in rats were evaluated. Female rats were fed from conception until day 9 of lactation diets containing 21% wheat protein (21W), 21% casein + methionine (21CM) or 11% casein + methionine (11CM). At parturition, dams were kept in their normal environment (20 degrees C) or were exposed to crowded conditions or an elevated ambient temperature (30 degrees C). Feeding poor quality protein (21W) or a lower amount of high-quality protein (11CM) reduced day 8 pup weights and average daily gains (ADG). Pup ADG's nursed by crowded dams fed either 11CM or 21CM were greater than those of pups nursed by noncrowded dams. Pup ADG's were reduced by heat exposure in dams fed 21CM but not in pups raised by dams fed diets reduced either in protein quality (21W) or protein quantity (11CM). Thus lactation performance was not further reduced by heat exposure in dams fed poor-quality wheat protein in spite of reduced food consumption and increasing lactation weight loss in these dams. The study indicates that lactating rats have considerable ability to raise their litters under potentially adverse conditions. PMID- 1745673 TI - Tectectomy in the cyclopean salamander. AB - In an Ambystoma larva with both natural eyes removed and one eye grafted atop the head (Cyclops preparation), vision-dependent behavior usually recovers from the enucleation inherent in the operation, but the optically activated skin blanching reaction reappears in a very small number of instances. In the present studies, while the latter trend continued for the conventional Cyclops preparation, tectectomy concurrent with the ectopic eye transplantation resulted in a several fold increase in the recovery of blanching competency. Some 60 percent of the tectectomized Cyclops animals exhibited the same Hogben-Slome pigmentation indices as larvae with one natural eye intact (controls). As measured planimetrically with an image analyzer, the pigment spots (melanosome containing portions of dermal melanocytes) contracted to the same extent in the blanch competent Cyclops animals as in controls with a single natural eye. PMID- 1745674 TI - Endocrinological and behavioral changes associated with the onset of incubation in the duck. AB - Plasma levels of prolactin were measured during the onset of incubation in ducks. A rapid rise in prolactin levels from a mean of 5.7 to 33.1 ng/ml occurred during the formation of the final 20% of the clutch; during which the females increased their nest-box occupancy from 9.9 to 22.2 hours per day. A pronounced decrease in plasma progesterone levels, but not estradiol, occurred in females in the days immediately preceding the onset of incubation and termination of egg laying. A similar decrease in plasma LH occurred. Plasma corticosterone levels also decreased during the transition from egg laying to incubation. In male ducks, who play no role in incubation, LH remained constant until well into incubation when it decreased. Changes in plasma levels of prolactin are discussed in relation to tactile stimulation from the clutch and nutritional stress. PMID- 1745675 TI - Metabolic changes of several adipose depots as caused by aging. AB - In this study, metabolic changes of several adipose depots as caused by aging were investigated. Key enzyme activity of glutaminolysis, pentose-phosphate pathway and Krebs cycle were measured. The rates of lipogenesis from 3H2O, lipoprotein lipase (LPL) activity and rate of lipolysis in vitro were also determined. The results obtained indicate a reduced capacity for lipogenesis in several adipose depots by aging. The authors concluded that hypertrophy of adipose tissue reported during aging is possible due to increased LPL activity and reduced rate of lipolysis. PMID- 1745676 TI - Serum corticosterone in fetal mice: sex differences, circadian changes, and effect of maternal stress. AB - The serum concentration of corticosterone was examined in control and stressed pregnant female mice (Mus domesticus) as well as male and female fetuses due to our interest in the behavioral effects of material stress on offspring in mice. Pregnant females were restrained under flood lights (2 sessions/day, 45 min/session) from Day 13-17 of pregnancy. On Day 17 of pregnancy a significant increase in maternal serum corticosterone was exhibited 1 h after the onset of a stress session, and serum corticosterone did not return to baseline until 16 h later. We also observed a significant increase in serum corticosterone in male fetuses during the first 4 h after maternal stress, while no significant change in serum concentration of corticosterone was observed in female fetuses throughout 24 h after maternal stress. Daily variation in serum concentration of corticosterone was also determined at 4-h intervals in pregnant mice and their fetuses from Day 16-18 of pregnancy. Pregnant females maintained on a 12 L:12 D cycle exhibited peak serum corticosterone concentrations at and just before the onset of the darkness. Daily fluctuations in serum concentrations of corticosterone in male and female fetuses reflected the pattern observed in the mothers. A sex difference in serum corticosterone in fetuses was observed at some, but not all times of the day, with the difference being greatest during the dark phase of the mother's light:dark cycle. PMID- 1745677 TI - The effect of cholecystokinin-octapeptide on food intake and consummatory behavior in lactating rats. AB - Rats are less sensitive to the satiating effect of CCK-8 during some reproductive states such as estrus and proestrus, and in ovariectomized rats following the administration of estradiol and progesterone. The sensitivity of rats to CCK-8's effect on food intake decreases as lactation progresses. During lactation, prolactin and progesterone levels are elevated. Implantation of ectopic pituitaries increases prolactin levels in males and females as well as progesterone levels in females. To evaluate whether or not prolactin elevation modifies CCK's effect on feeding, we studied the effect of CCK-8 on food intake during the early dark cycle in male and female rats implanted with ectopic pituitaries. As previously demonstrated, prolactin levels were elevated in both male and female pituitary-implanted rats and progesterone levels were elevated in the female rats. CCK-8 inhibited food intake in sham-operated male rats, but did not reliably decrease early dark cycle food intake in sham-operated or pituitary implanted female rats or pituitary-implanted male rats. Thus an elevation in prolactin levels does not appear to modify the effect of CCK-8 on food intake in female rats. We also evaluated the effect of CCK on consummatory and maternal behavior in lactating rats. CCK-8 altered the meal patterns of lactating rats primarily by decreasing the rate of food consumption and increasing the latency to the first meal. The latency to the first meal of rats receiving CCK was increased during early and mid-lactation and the PW period, but not during late lactation compared to that of the saline-injected rats. CCK-8 did not modulate any of the maternal behaviors studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745678 TI - Fasting-induced rise in locomotor activity in rats coincides with increased protein utilization. AB - The aim of this study was to investigate the possible relation between the modifications in locomotor activity (on running wheel) which occur during prolonged fasting and changes in the utilization of energy reserves. In 18-week old rats, we found that the rate of body mass loss reflects the changes in nitrogen excretion that occur over three phases of fasting: (I) initially decreasing, (II) maintained at a low level and (III) increasing. Locomotor activity started to increase during phase II without a change in its nycthemeral pattern. By contrast, the 10-fold higher daily locomotor activity that occurred in phase III was marked by a higher proportion of diurnal activity. Using 9-, 18 , and 33-week-old rats, in order to obtain a different timing in the metabolic changes during fasting, we could confirm the coincidence between the later rise in locomotor activity and the occurrence of phase III. Refeeding of rats of either age in phase III rapidly suppressed fasting-induced changes in locomotor activity. These data accord with the idea that behavioral changes reflecting the search for food are triggered by a later and reversible change in the utilization of body protein vs. lipid stores during prolonged fasting. PMID- 1745679 TI - Refeeding after the late increase in nitrogen excretion during prolonged fasting in the rat. AB - Recovery of body mass, food intake and body composition was studied in the laboratory rat after the late increase in nitrogen excretion that characterizes prolonged fasting in mammals and birds. The rats lost 43% of their body mass during 13 days of food deprivation. They all regained their prefasting body mass within a shorter period of 11 days of refeeding. These results confirm that the late increase in nitrogen excretion in rats, as in spontaneously fasting birds, is reversible and is a part of the physiological adaptations to long-term food deprivation. Water intake of the rats continuously decreased during fasting, and the animals virtually stopped drinking as protein utilization increased. On refeeding, changes in water intake paralleled those in food intake. The refed rats progressively increased their daily food intake, that was always higher than the prefasting value (8.0-10.4 vs. 6.7% of body mass). The comparison of organ weights between fed and ad lib refed rats of similar body weight indicates that muscle mass was regained earlier than body fat during refeeding. The laboratory rat therefore appears to be a good experimental model to investigate the metabolic and behavioural changes that occur during spontaneous anorexia and refeeding in wild animals. PMID- 1745680 TI - The effects of short day exposure on seasonal and circadian reproductive rhythms of female golden hamsters. AB - Four groups of female golden hamsters were exposed to short photoperiods (SP, LD 10:14) for 4, 14, 20, or 27 weeks and tested for physiological markers (uterine weight and estrous cycles) and behavioral (lordosis, approach and aggressive behaviors) measures while in contact with a stud male. After behavioral testing, females were ovariectomized and, during the next 2 weeks, were tested twice more (with a stud male) after replacement with 0.33 microgram (low dose) and 1.0 microgram (high dose) EB plus progesterone (500 micrograms). Results show that, after 14 weeks of SP conditions, uterine weights and percentage of females showing normal estrous cycles are at a minimum. This is mirrored by minimal levels of lordosis and maximal levels of aggressive and approach behavior at week 14. Physiological measures did not fully recover (to preregression levels) until week 27; however, behavioral measures show an earlier recovery by week 20. SP exposure also affects the circadian patterning of behaviors: Females that show lordosis at week 14 did so later in the day than did females tested at other weeks. Females in the regressed state also fail to show a significant decrease in approach behaviors (and a significant increase in receptive behaviors) over the course of the circadian day, a pattern seen in nonregressed females. Following hormone replacement with the low EB (+P) dose, females do not become receptive; however, at the higher dose, all but the week 14 group show increased receptivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745681 TI - The effects of preexposure to the drug on state dependent retention. AB - The present experiment examined whether previous experience with a drug would decrease the potential of the drug to produce state dependent retention (SDR) for a passive avoidance response in rats. In the first experiment, a single injection of sodium pentobarbital (20 mg/kg) given on six consecutive days before the training day slightly reduced, but did not block, pentobarbital-induced SDR. In Experiment Two, four preexposure injections of 5 IU/kg insulin reduced the magnitude of memory loss produced by administration of the hormone prior to training. As with pentobarbital, however, preexposure to insulin did not completely block the amnestic effect of the hormone. A subsequent experiment demonstrated that the decrease in the strength of insulin-induced SDR in insulin preexposed rats was not the result of enhanced acquisition. Collectively, these data indicate that noncontingent preexposure to an amnestic treatment may decrease the magnitude of memory loss that would normally result from the administration of that treatment during training. PMID- 1745682 TI - Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice. AB - Previous studies have indicated that manipulation of activity levels can modify characteristics of sleep/wake and activity rhythms. The generality of these observations was evaluated by simultaneously measuring drinking and sleep/wake rhythms while mice had free or no access to a running wheel in constant conditions (DD). Robust circadian rhythms in all parameters were observed in the "wheel free" (unrestricted) condition. When wheels were locked, the peak amplitude of the sleep/wake circadian rhythm decreased by approximately 50% without affecting the amplitude of the drinking rhythm. Total wake time decreased 11% per circadian day when wheels were locked with increases in both NREM and REM sleep. Whereas the amplitude of the drinking waveform was unaffected, wheel restriction caused an equivalent increase in period length (tau) for both rhythms. These results indicate that, unlike the generalized effects of activity on tau, activity restriction influences on rhythm amplitude do not generalize to all behavioral and/or physiological variables. This work also supports the notion that activity influences on sleep/wake rhythm amplitude reflect behavioral "masking" rather than a fundamental change in the direct coupling mechanisms of the biological clock. PMID- 1745683 TI - Male saliva cues and female social choice in Mongolian gerbils. AB - Adult female Mongolian gerbils (Meriones unguiculatus) are preferentially attracted to saliva from adult nonsibling males when paired with saliva from male siblings. The focus of the present study was to evaluate the potential role of saliva in the formation of reproductive units. In Experiment 1, olfactory directed investigations and mate choices of estrous females housed with their brothers and unrelated males were examined. Females sniffed unrelated males more frequently than siblings and were more interested in sniffing the mouth area than other body areas. Importantly, they also solicited and mated exclusively with unrelated males. The purpose of Experiment 2 was to ascertain the origin of the behaviorally active components of saliva by transecting the parotid salivary duct (PDT). When either sibling saliva or water was paired with saliva from a nonsibling PDT male, females did not show the typical preference for saliva from nonsiblings. When social preferences were examined in Experiment 3, virtually all females preferred intact nonsibling males to either PDT nonsibling males or siblings. Results from this study support the hypothesis that saliva is an important oral cue used by females in the selection of sociosexual partners. Furthermore, the parotid gland appears to be a significant source of salivary chemosignals. PMID- 1745684 TI - Does starch taste like Polycose? AB - Rats are capable of tasting or detecting maltooligosaccharides (e.g., Polycose) and starch in water, two substances that are bland to humans. Because both substances are glucose polymers, it has been suggested that they may be detected by the same mechanism. The present experiments examined whether rats conditioned to avoid one of these substances also avoid the other. Rats were injected with lithium chloride after being allowed to drink a 3% corn starch suspension. These rats subsequently avoided corn, potato, rice, and waxy maize (high-amylopectin) starch but did not avoid 0.1-3% Polycose Rats treated with lithium chloride after ingesting 3% Polycose avoided 3% and 0.5% Polycose, but they did not avoid 3% corn starch, 6% corn starch, or 3% waxy maize starch. These results indicate that rats can discriminate between starch and Polycose (maltooligosaccharides). It therefore seems likely that Polycose and starch have different sensory qualities. PMID- 1745685 TI - Duration of mating relates to fertility in mice. AB - In normal mating, house mice vary dramatically in the number and duration of intromissions that precede ejaculation. Also, some proportion of inseminations typically fails to yield litters. The present studies involved systematic observations of matings of females in natural estrus with males of proven fertility. After standardized observation of mating behavior culminating in ejaculation and a sperm plug, females were allowed to produce litters in undisturbed conditions. In two replications, greater numbers of intromissions and a longer latency from first intromission to ejaculation both correlated positively with litter size. PMID- 1745686 TI - A system for automated recording and analysis of feeding behavior. AB - We have designed and implemented a system that utilizes a network of top-loading balances digitally interfaced to a Macintosh computer. The system simultaneously collects two forms of data which allow the evaluation of the animal's biting and/or licking behavior in addition to cumulative food intake and meal patterns. The system is capable of resuming data acquisition following a power failure without user intervention. Plexiglas cages utilized with the system features adjustable tunnel feeders and are appropriate for use with small rodents. Given appropriate caging, the system may be utilized to evaluate the feeding behavior of other species. PMID- 1745687 TI - Differential effects of unilateral optic tract transections and visual cortical lesions upon a pattern discrimination in albino rats with removal of one eye at birth. AB - Previously we have demonstrated that adult rats with one eye removed at birth (OEB) relearn a black-white discrimination faster than control rats monocularly enucleated at maturity (OET), when relearning is conducted after lesions of the visual cortex contralateral to the remaining eye. This faster relearning phenomenon is considered to be one behavioral expression of the functioning of the expanded uncrossed visual pathways resulting from monocular at birth. The present study was concerned with the question of whether the same phenomenon can be observed in the discrimination between alternating black and white stripes oriented horizontally and vertically. Two experiments were carried out. In the first experiment, which is a replication of one of our previous studies, relearning was conducted after the visual cortical lesions contralateral to the remaining eye. The results were consistent with those of the previous one in which neither OEBs nor OETs were found able to relearn the discrimination. In the second experiment, relearning was conducted after transections of the optic tract contralateral to the remaining eye. It was shown that under this condition both OEBs and OETs could relearn the discrimination, and furthermore, that OEBs restored the habit faster than OETs. Possible mechanisms underlying the difference in the results from the two experiments were discussed. PMID- 1745688 TI - Cholecystokinin promotes sleep and reduces food intake in diabetic rats. AB - It has been reported that systemic injections of cholecystokinin (CCK) elicit the behavioral characteristics of satiety, including sleep, in rats. CCK is a potent stimulator of insulin secretion, and insulin is hypothesized to be involved in sleep and feeding regulation. The purpose of the current experiments was to study the possible role of endogenous insulin in the food-intake-reducing and hypnogenic effects of intraperitoneally (IP) administered CCK. Normal and streptozotocin (STR)-diabetic rats were injected with isotonic saline or CCK (10 and 50 micrograms/kg) at dark onset, and sleep-wake activity was determined for the next 12 h. There were no significant differences between the baseline sleep wake activity of normal and diabetic rats. IP injection of CCK elicited a selective increase in nonrapid-eye-movement sleep in both groups during the first postinjection hour. In a separate experiment, the effects of CCK (10 micrograms/kg) on food intake were determined in control and diabetic rats; CCK suppressed the 1-h food intake in both groups. In a third experiment, the effects of CCK treatment (50 micrograms/kg) on plasma insulin levels were determined. In normal rats, CCK elicited a two-fold increase in plasma insulin concentration, whereas diabetic rats had a significantly lower basal insulin level which was not affected by CCK treatment. We conclude that hypnogenic and food-intake-reducing effects of exogenously administered CCK are closely associated; however, pancreatic insulin does not play a significant role in either of these effects. PMID- 1745689 TI - Possible interaction between the inferior colliculus and the substantia nigra in audiogenic seizures in Wistar rats. AB - Male Wistar rats were tested for sensitivity to audiogenic seizures (AS; 110 dB), using an audiogenic severity index (SI). Sensitive (S) animals were subjected to bilateral lesion of the inferior colliculus (IC) and/or the lateral lemniscus (LL). Resistant (R) animals were subjected to bilateral lesions of the IC, unilateral sequential lesions of the substantia nigra reticulata (SN) and/or IC (contralateral to one another), and unilateral thalamic and sham lesions. Bilateral lesions of the IC and LL abolish AS in S rats. Lesion of the SN resulted in more pronounced sensitivity to AS than unilateral lesion of IC, in R rats. When the SN lesion was contralateral to a previous IC lesion, the effect was not only an increase in the SI, but also a reversal of the asymmetry generated by IC lesion. Although the behavioral effects resulting from IC lesions are due to alterations in the primary structures involved in the origin of AS, unilateral SN lesions can alter critical substrates of sensorimotor integration involved in the control and expression of AS. PMID- 1745690 TI - Antide (Nal-Lys GnRH antagonist) suppression of pituitary-testicular function and sexual behavior in group-living rhesus monkeys. AB - The ability of a Nal-Lys gonadotropin releasing-hormone antagonist (Antide) to suppress pituitary-testicular function and male sexual behavior was studied in seven group-living adult male rhesus monkeys. Each male received a single 15 mg/kg b.wt. subcutaneous injection of Antide dissolved in equal volumes of propylene glycol and sterile water. Prior to Antide treatment, and at two, four, and eight weeks after Antide, males received an IV bolus of GnRH (50 ng/kg) to assess pituitary and testicular function. For four weeks before and eight weeks after Antide treatment, blood samples and behavioral observations were collected three times weekly in a 74-member heterosexual group. Antide levels increased to more than 150 ng/ml 24 h postinjection and remained above 15 ng/ml for 30 days postinjection. Circulating LH and T were significantly reduced within 24 h following Antide, and remained significantly lower than pretreatment levels in all males for 5 weeks after Antide. T levels rose above 1 ng/ml while Antide levels were still significantly elevated in four males. Both LH and T returned to pretreatment levels by seven weeks post-Antide and then showed a second significant decrease during the eighth study week. Pituitary responsiveness to exogenous GnRH was reduced by Antide and remained below pretreatment levels eight weeks after Antide treatment. Testosterone secretion in response to exogenous GnRH was significantly reduced at two and four weeks post-Antide, but was at pretreatment levels by eight weeks after Antide. Male sexual behavior declined significantly within one week after Antide treatment, almost ceased completely by four weeks after Antide, and returned to pretreatment levels by seven weeks post Antide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745691 TI - Thermal stress modulates temporal patterns of responding on a multiple DRL-FR schedule. AB - To investigate temporal changes in behavior induced by moderate cold temperatures, rats performing on a multiple differential-reinforcement-of-low rate (DRL) fixed-ratio (FR) schedule were exposed to ambient temperatures of 2, 8, 16, and 24 degrees C. DRL response rates markedly increased with decreasing cold temperatures, while FR response rates remained unchanged. In addition, as ambient temperatures decreased, the interresponse time (IRT) distribution of DRL responses shifted toward shorter times and short IRT bursts increased. Compared with cold effects, exposure to 38 degrees C heat induced decreases in both DRL and FR response rates which were associated with increases in long IRTs. Decreases in reinforcement frequency was associated only with the DRL schedule in cold, and with both DRL and FR schedules during heat exposures. The distinct effects of cold and heat on both DRL and FR responding suggest that the increases in DRL response rates and shifts in IRT distribution are unique to cold, and are not due to general effects of nonspecific thermal change in the ambient environment. PMID- 1745692 TI - Rapid reentrainment of the circadian clock itself, but not the measurable activity rhythms to a new light-dark cycle in the rat. AB - Experiments were performed to determine if the circadian clock reentrains more quickly to an 8-hour phase shift in light-dark (LD) cycles than does the overt rhythm of activity. To investigate the reentrainment of the clock itself to an 8 hour advance or delay in the LD cycle, the rats were released into constant darkness only two or three days after a shift in LD cycle, and the amount of the phase shift of the clock itself was estimated from where free-running rhythm started by backward extrapolation. If the circadian clock could rapidly reset itself to the new LD cycle, it was predicted that the free-running rhythm of activity would start from near the dark period of the new LD cycle rather than the preceding one. When rats were released into constant darkness three days after the LD cycle was advanced by 8 hours, the activity of the free-running rhythm started near time of dark period of the new LD cycle in all rats (n = 16). When rats (n = 24) were released into constant darkness two days after the LD cycle was advanced by 8 hours, 12 rats started the activity near time of dark period of the new LD cycle, while 9 rats started the activity near time of dark period of the preceding LD cycle. The remaining 3 rats showed the activity of the free-running rhythm near intermediate phase (transient phase). On the other hand, when the rats were not released into constant darkness after LD cycle was advanced by 8 hours, it took 6.4 days for activity rhythm to reentrain to the advanced LD cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745693 TI - Maintenance and decline of the suppression of infanticide in mother rats. AB - Virgin female rats kill foster neonates, whereas newly parturient mothers do not. We demonstrated previously that this tendency to kill is suppressed shortly prepartum, presumably by physiological factors. In this study, we show that a) suppression of infanticide is maintained through the first two weeks of lactation; b) the mothers that do not kill foster neonates are not necessarily the same mothers that respond maternally toward older foster pups, and those that kill neonates are not necessarily the same ones that are nonmaternal to older pups, the two behaviors being somewhat independent; and c) some virgins can be induced to be noninfanticides by prolonged exposure to young, but only under special testing conditions not required by actual mothers, which are nonkillers of foster young. This suggests that the maintenance of the suppression of infanticide in mothers owes something to the special circumstances of lactation other than continued exposure to young. PMID- 1745694 TI - Rapid odor conditioning in newborn rabbits: amnesic effect of hypothermia. AB - Rabbit pups are completely dependent on a maternal pheromone for the release of suckling behavior. However, if the mother is perfumed prior to nursing, pups will learn to respond to the novel odor with the characteristic nipple-search behavior in just one 3-4 min nursing episode. In a first investigation of the processes underlying this recently developed learning paradigm, time-dependent effects of hypothermia on retention of the task could be demonstrated. Thus pups whose whole body was cooled to a mouth temperature of 7 degrees C immediately after conditioning (n = 10) and tested 24 h later for 3 min on a perfumed fur did not differ significantly in their search response from naive, untreated controls (n = 10). In contrast, pups cooled 4 h after conditioning (n = 10) demonstrated clear retention of the learned response and searched as vigorously as conditioned but uncooled animals (n = 10). As pups of all groups demonstrated normal nipple search behavior when tested on a lactating doe, the deficits associated with immediate cooling appear to have been specific to the learning task and time of treatment. PMID- 1745695 TI - Lipopolysaccharide increases ambient temperature preference in C57BL/6J adult mice. AB - The hypothesis was tested that animals exposed to a potentially dangerous endotoxin would attempt to behaviorally elevate their body temperature, perhaps in an effort to engage those immunological mechanisms which would counter the adverse effects of the endotoxin. Lipopolysaccharide (LPS) from Escherichia coli injected subcutaneously (100 micrograms) in adult C57BL/6J mice increased gradient temperature preference by 2.4 degrees C over saline controls. The increase in body temperature of 1.1 degrees C after LPS injection was due to the preference for higher ambient temperatures and was not the result of a systemic reaction to LPS (animals not exposed to the gradient did not differ in body temperature). In summary, our data indicate that adult mice self-induce a febrile response, perhaps as an attempt to compensate for the physiological impact of the endotoxin. PMID- 1745696 TI - Community-based psychiatry: long-term patterns of care in South-Verona. AB - Community-based psychiatry has attracted a wide interest in the last 20 years. However, the evidence in the literature on monitoring and evaluating community psychiatric services for a long period of time is scanty. The aim of this monograph is to present the results of a number of evaluative studies, covering a ten-year period, conducted in South-Verona, an area of 75,000 inhabitants in Northern Italy, where a new community-based system of care, the South-Verona Community Psychiatric Service (CPS), has operated since 1978. This system, which is based on the provisions of the Italian psychiatric reform, is alternative to the old hospital-centred system of care, and provides care and support to all types of patients, without back-up from the mental hospital, where only a few old long-stay in-patients continue to reside. In the first part of the monograph, trends in the provision of psychiatric care in the period 1979-1988 are presented, using the South-Verona Psychiatric Case Register (PCR). Both one-day and one-year prevalence figures and incidence rates are lower than in other register areas outside Italy, partly because of the smaller number of specialized out-patient services available in South-Verona and partly because of less use of in-patient care in our area. Moreover, there is a tendency in Italy to care for elderly patients in geriatric institutions outside the psychiatric system. Most of the patients seen in any year are treated without in-patient care. This applies to all diagnostic groups, except affective psychosis. Rates of compulsory admission dropped dramatically after the reform. The total number of admissions to all in-patient psychiatric facilities (including private hospitals) in 1988 is only 8.4% lower than that found in 1977 (one year prior to the reform), while the mean number of occupied beds in 1988 was 47% lower than in 1977. In South-Verona point-prevalence of long-stay in-patients has slowly decreased over the years and there is a negligible build-up of new long-stay in-patients. The South-Verona CPS is now taking care of most psychiatric patients who, before the reform, would have been admitted to the mental hospital and become long-stay. These patients, who may be defined as long-term patients in the community, have consistently accumulated since 1981 and are making high use of psychiatric community services.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745697 TI - Testicular function, social rank and personality among wild baboons. PMID- 1745698 TI - Cortisol escape from suppression by dexamethasone during depression is strongly predicted by basal cortisol hypersecretion and increasing age combined. AB - We determined baseline 0800h plasma cortisol concentrations, 24-hr urinary free cortisol (UFC) excretion, the post-dexamethasone cortisol values at 0800h and 1600h, and the 0800h dexamethasone concentrations in 60 depressed patients categorized according to the DSM-III. Up to 59% of the variability in the 0800h post-dexamethasone cortisol values could be explained by the multiple regression on UFC, 0800h basal plasma cortisol, age (all positively related), and dexamethasone concentrations (negatively related). The 1600h post-dexamethasone cortisol data were best explained (i.e., 55% of the variance) by the multiple regression on basal plasma cortisol, UFC (positive) and dexamethasone (negative). After controlling for UFC, baseline plasma cortisol, and age no significant effects of the depressive state (diagnostic classification or severity of illness) on the post-dexamethasone cortisol values could be detected. It can be deduced that cortisol non-suppression during depression is related strongly to baseline cortisol hypersecretion and increasing age. These factors are additive and contribute independently towards cortisol escape from suppression by dexamethasone. PMID- 1745699 TI - The relationship between testosterone levels and cognitive ability patterns. AB - The cognitive performance of normal men and women was studied, grouped according to whether the subjects had relatively high or low salivary testosterone (T) concentrations. Men with lower T performed better than other groups on measures of spatial/mathematical ability, tasks at which men normally excel. Women with high T scored higher than low-T women on these same measures. T concentrations did not relate significantly to scores on tests that usually favor women or that do not typically show a sex difference. These results support suggestions of a nonlinear relationship between T concentrations and spatial ability, and demonstrate some task specificity in this respect. PMID- 1745700 TI - Psychological and serum homovanillic acid changes in men administered androgenic steroids. AB - We report a difference in the response of serum homovanillic acid (HVA) and in the performance of some psychological tasks before and after the administration of testosterone enanthate (TE, 100 or 300 mg/wk) or nandrolone decanoate (ND, 100 or 300 mg/wk) for 6 wk to healthy men. Serum HVA was significantly increased in both the low- and high-dose ND groups, from 8.4 +/- 1.0 and 8.7 +/- 0.5 pmol/ml (mean +/- SE) to 11.6 +/- 1.7 and 10.7 +/- 1.1 pmol/ml respectively. No significant changes in HVA were observed for the groups administered TE, nor in 5 HIAA for any of the groups. The influence of ND on the dopaminergic system, which is reflected in increased serum HVA, appears to be independent from the psychological effects which were produced by both androgens. The only change in psychomotor test performance was an improvement in the first trial of a pegboard task. All subjects except those receiving ND (100 mg/wk) were significantly more optimistic in the prediction of their own performance for all nondominant hand tasks (pegboard and finger tapping). The "hostility" and "resentment and aggression" subscales of the MMPI increased significantly in all groups, more so in the high-dose groups. PMID- 1745701 TI - Two studies of menstrual synchrony: negative results. AB - In 1971 McClintock reported menstrual synchrony in pairs and groups of women who spent time together. The two studies reported herein, based on the methods and research design introduced by McClintock, fail to replicate her results. The first study is of a sample of 132 women who were sorority members or roommates of sorority members living on the campus of a large coeducational state university. The second study is of a sample of 24 women who were members of a cooperative house near the same university. In the subjects from both studies, the final mean onset absolute difference is greater than the initial mean onset absolute difference, and there are more nonsynchronous pairs of subjects than synchronous pairs. The sample from the sorority study was progressively reduced to exclude those subjects with irregular menstrual cycle lengths and those pairs in which one subject was taking oral contraceptives. Menstrual synchrony did not emerge in the reduced sample. Thus, whether or not menstrual synchrony occurs among women who spend time together should still be considered a hypothesis requiring further investigation. PMID- 1745702 TI - GH response to GHRH before and after meals at different hours of the day in obese patients. AB - In normal subjects several factors are involved in the regulation of the GH response to GHRH, such as nutritional status, metabolic fuels and neurotransmitters. We previously have shown a paradoxical increase in the GH response to GHRH after meals in obese patients, in contrast to the blunted GH response observed after feeding in normal subjects. We have further investigated this phenomenon, studying the GH response to GHRH before and after meal at three different hours during the day in 10 obese patients, aged 18-35 yr, in comparison to that in eight normal women, aged 20-35 yr. GHRH was injected in a fasting state or 1 hr after a standard meal (800 KCal). In obese subjects, after food ingestion the peak GH response to GHRH was increased at 0900h and 1300h and was significant when the patients were tested after lunch (1300h). On the contrary, in the evening the GH response to GHRH remained unchanged, both before and after feeding. These data point to an altered sensitivity of GH secretion to metabolic signals in patients with obesity. PMID- 1745703 TI - Chronic opioids impair acquisition of both radial maze and Y-maze choice escape. AB - Chronic morphine impaired acquisition of two dissimilar behavioral tasks. In the radial maze, the performance of saline-treated and morphine-treated groups diverged with the latter failing to improve despite extensive training. In contrast, rats treated with naltrexone became skilled in the procedure 2-4 times as rapidly as saline controls. Withdrawal of treatment significantly improved performance of morphine-treated rats, with no change for rats treated with saline or naltrexone. When a second group of rats was extensively trained prior to instituting chronic morphine treatment, performance scores were not affected, suggesting that morphine does not impair spatial working memory despite subjective evidence of other gross behavioral effects, such as ataxia. In the Y maze choice escape task, acquisition of a response strategy was significantly impaired in rats that had been previously treated with morphine for 17-21 days, despite clear indications that morphine-treated rats were sensitive to the aversive stimulus. PMID- 1745704 TI - Does metergoline selectively attenuate 5-HT mediated prolactin release? AB - Administration of the non-selective 5-HT receptor antagonist metergoline (0.5 mg/kg) to male rats attenuated the prolactin response to the 5-HT releasing agent d-fenfluramine (7.5 mg/kg) but not to the dopamine receptor antagonist haloperidol (1.5 mg/kg). In contrast, in healthy male volunteers, pretreatment with metergoline (4 mg orally) abolished the prolactin response to intravenous haloperidol (5 micrograms/kg). The findings suggest that in humans blockade of a prolactin response by a conventional oral dose of metergoline cannot be taken as evidence of involvement of 5-HT-mediated mechanisms. PMID- 1745705 TI - Evidence that genetic differences in habituation and GABAergic mechanisms may be related to sensitivity to ethanol and development of ethanol tolerance in mice. AB - Habituation to a test environment following daily exposure for 5 days was examined in three genetically different strains of mice. C57 animals showed significant habituation to the new environment already on the second day. The habituation of NMRI mice was significant on the third day, whereas CBA mice showed no habituation at all during the experimental period. There was no difference between the animal strains in learning capacity in a passive avoidance test, but CBA mice displayed a significant increase in latency in their performance. When tested for sensitivity to the convulsant actions of GABAergic antagonists, picrotoxin produced seizures at lower doses in CBA as compared to NMRI and C57 mice, whereas there was no difference between the strains in the seizure activity produced by the specific GABA receptor antagonist bicuculline. When the animals were tested for sensitivity to ethanol in a horizontal wire test, ethanol (2 g/kg, IP) produced muscle relaxation in CBA mice whereas the performance of NMRI and C57 was not affected. A large dose of ethanol (4 g/kg, IP) produced a significantly longer sleeping time in CBA mice as compared to NMRI and C57 animals. Ethanol-produced hypothermia was, however, similar in all animals. Environment-dependent development of tolerance to ethanol following daily injections of ethanol for 4 days was examined. C57 mice showed the most rapid development of tolerance towards ethanol's hypnotic actions, whereas CBA mice showed no tolerance to this effect of ethanol. No difference between the strains to the development of tolerance to ethanol's hypothermic effects was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745706 TI - Reversal by tetrahydroaminoacridine of scopolamine-induced memory and performance deficits in rats. AB - The effects of the cholinesterase inhibitors physostigmine and tetrahydroaminoacridine (THA) on memory and performance deficits induced by scopolamine were studied using an operant delayed non-matching to position task. No effect was seen on the performance of rats when treated with either physostigmine (0.1 mg/kg IP) or THA (1 mg/kg IP) alone. However, the performance deficits induced in the task by scopolamine (0.03 mg/kg SC) were reversed by the same doses of the cholinesterase inhibitors. PMID- 1745707 TI - Differential effects of caffeine on free recall after semantic and rhyming tasks in high and low impulsives. AB - The effects of caffeine on free recall after acquisition on semantic and rhyming tasks were examined. Following a between-subjects design, high and low impulsive male postgraduate students were administered placebo and four doses of caffeine citrate (1, 2, 3 and 4 mg/kg body weight) in a laboratory situation. A double blind procedure was adopted for drug administration. The study supports the following conclusions: (1) under no drug condition, high impulsives recall more after semantic acquisition while their counterparts, the low impulsives, recall more after rhyming acquisition; (2) caffeine facilitates recall in high impulsives after rhyming acquisition but hinders it after semantic acquisition; (3) caffeine does not reliably influence recall of low impulsives. PMID- 1745708 TI - The Hillside Akathisia Scale: a reliability comparison of the English and German versions. AB - Akathisia usually consists of two components, subjective restlessness and typical movements such as shuffling of the legs, pacing, shifting weight from one leg to the other, and rocking movements of the trunk. The ability to measure akathisia reliably is essential for the assessment of treatments for akathisia and for the evaluation of drug-induced side effects in general. To date, investigators have generally used self-constructed assessment scales without reporting data about reliability or validity. The Hillside Akathisia Scale (HAS) has two subjective and three objective items for which anchored rating points are provided. Reliability was 0.89 for the HAS total score. Reliability for rating subjective symptoms ranged from 0.86 to 0.92, and the objective scores ranged from 0.51 to 0.89. The correlation between HAS and a global assessment of akathisia (modified CGI) was 0.87. These values compare favorably with the original report on the scale indicating that the Hillside Akathisia Scale can validly quantify akathisia with a satisfactory degree of interrater reliability. PMID- 1745709 TI - Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans. AB - The effects of oral nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine infusions were studied in cocaine-using volunteers. Nifedipine, 10 mg or placebo, was administered 20-25 min before placebo, 20 mg, or 40 mg cocaine, using a repeated measures randomized double blind design. The variables measured were self-reported subjective effects, general behavior rated by two observers, blood pressure and heart rate. Cocaine produced the expected dose-related effects on subjective and cardiovascular measures. Nifedipine pretreatment attenuated some subjective effects of cocaine. Nifedipine directly reduced blood pressure but did not antagonize the effects of cocaine on blood pressure. These findings suggest that dihydropyridine calcium channel modulators may be useful compounds in the clinical management of cocaine users. PMID- 1745710 TI - Perphenazine decanoate and cis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients. Serum levels at the minimum effective dose. AB - Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long term maintenance treatment of schizophrenia. PMID- 1745711 TI - Effect of sucrose consumption on alcohol-induced impairment in male social drinkers. AB - Two studies were conducted to examine the interaction between sucrose and ethanol in normal young fasting adult males. The first experiment employed a 3 (100 g sugar, 35 g sugar, 0 g sugar) x 3 (alcohol, placebo and sober) factorial design, which was carried out double-blind using aspartame to ensure that all the drinks were equally sweet. Subjects were tested for mood, memory, subjective intoxication and psychomotor performance at baseline and at times up to 3.5 h after ingestion of the drinks. An alcohol by sugar interaction was seen at 0.5 after drinking. Sugar attenuated alcohol intoxication at this time without influencing blood alcohol levels. Contrary to previous reports, the combination of alcohol and sugar failed to produce significant hypoglycemia, or any of the adverse behavioral effects associated with hypoglycemia, at later times after drink ingestion. The second experiment involved a simpler design, carried out single-blind in which the subjects receiving no sugar did not get aspartame. This was to rule out the possibility that aspartame was exacerbating alcohol intoxication instead of sugar attenuating it. The second experiment also showed that sugar can attenuate alcohol intoxication in fasting humans without altering blood alcohol levels significantly. PMID- 1745712 TI - Naloxone modulates the behavioral effects of cholinergic agonists and antagonists. AB - Peripheral glucose administration enhances memory in rodents and humans. Recent findings suggest that glucose may affect behavior, in part, by augmenting central cholinergic functions and by attenuating central opiate functions. The present experiments examined interactions between an opiate antagonist, naloxone, and cholinergic agents to determine whether the effects would parallel those found with glucose. Three behavioral measures were assessed: tremors, hyperactivity, and spontaneous alternation. Naloxone (1 mg/kg) significantly augmented tremors elicited by physostigmine (0.3 mg/kg). Naloxone (1 mg/kg) also attenuated increases in locomotor activity and impairments in spontaneous alternation performance elicited by scopolamine (1 and 3 mg/kg for activity and alternation measures, respectively). Thus, across three diverse measures, naloxone produced effects similar to those previously reported for glucose. These findings are consistent with the hypothesis that release of cholinergic activity from opiate inhibition may contribute to glucose effects on behavior. PMID- 1745713 TI - Sensitivity and tolerance to nicotine in smokers and nonsmokers. AB - We studied the responses of smokers and lifelong non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n = 8), non-smokers on a 30 mg patch (n = 8) and smokers on a 30 mg patch (n = 8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD = 3.7), 10.9 (SD = 4.2) and 4.1 (SD = 2.7) ng/ml in the three groups, respectively (P less than 0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (X Cmax 13.9 ng/ml, SD = 4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P less than 0.01) within the first hour, and seven dropped out (P less than 0.01) at 3-8 h due mainly to severe nausea, vomiting or headache (X Cmax 18.4 ng/ml, SD = 4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (X Cmax 7.9 ng/ml, SD = 3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication. PMID- 1745714 TI - Dissociation of multiple effects of acute LSD on exploratory behavior in rats by ritanserin and propranolol. AB - Rats tested for 1 h in the Behavioral Pattern Monitor (BPM) after injection of the mixed serotonergic agonist d-lysergic acid diethylamide (LSD) exhibit a behavioral profile similar to that produced by various hallucinogenic 5HT-2 agonists. The characteristic effects of the hallucinogens include suppression of locomotor and exploratory behavior and a preferential decrease in entries into the center of the BPM during the initial half of the test session. After LSD, the initial suppression of responding is followed by a subsequent increase in locomotor activity that is not observed with other serotonergic agonists. In the present studies, the 5HT-1 and beta-adrenergic antagonist d,l-propranolol and the 5HT-2 antagonist ritanserin were administered individually or in combination prior to the acute administration of LSD to test for the involvement of these receptor subtypes in the mediation of the effects of LSD in the BPM paradigm. Propranolol (20 mg/kg) abolished the initial suppression of activity induced by 60 micrograms/kg LSD without affecting the subsequent increase in locomotion. Conversely, 2.0 mg/kg ritanserin failed to block the initial suppressive effects of 60 or 120 micrograms/kg LSD, but attenuated the LSD-induced increases in activity during the second half of the session. The combination of propranolol and ritanserin prevented both these effects of LSD. By contrast, the more selective 5HT-2 agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) (0.27 mg/kg) produced an initial suppression of activity in the BPM that was blocked by 2.0 mg/kg ritanserin and was not followed by a subsequent increase in activity. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745715 TI - Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress. AB - Dose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male volunteers participated in a placebo and a lorazepam session, during which the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.6, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). Heart rate showed a dose-dependent decrease during rest with an ED50 of 0.13 mg lorazepam, while lorazepam had no effect on the cardiovascular and plasma catecholamine response magnitudes to the CWT. Subjective fatigue and reaction time increased significantly after 0.94 mg lorazepam, while at the same dose vigor decreased; state anxiety after the CWT was not influenced by lorazepam. These data show differential effects of lorazepam on cardiovascular, biochemical and psychological function. While heart rate was suppressed at low doses during rest and reaction time and subjective fatigue increased at doses which induced sedation, state anxiety and physiological response patterns to the CWT were not influenced by lorazepam. PMID- 1745717 TI - Scopolamine attenuates the motor disruptions but not the attentional disturbances induced by haloperidol in a sustained attention task in the rat. AB - Rats were trained to perform a sustained attention task that required the subject to insert its head into a cylindrical "observation tunnel" and wait for the presentation of one of three spatially separated visual stimuli located on the upper portion of the tunnel circumference. Detection of a briefly (0.125 s) presented "correct" stimulus, followed by the rats' forward nose poke, resulted in access to a reinforcement dipper lifted through the orifice in the floor of the tunnel. Nose pokes to the two incorrect stimuli resulted in a 5-s time-out period. The task maximized attention and minimized movement requirements. Performance was characterized in terms of accuracy (i.e. errors of omission, and errors of commission), time on task, and latency to respond to the stimuli (i.e., reaction time). Haloperidol (0.04, 0.08, and 0.16 mg/kg) increased errors of omission and reaction time. However, lack of significant correlations between these two measures suggested that attentional accuracy may be independent of motor slowing produced by this neuroleptic. Scopolamine (0.2 mg/kg) alone increased both errors of omission and commission, but did not affect reaction time to correct stimuli. The sustained attention task as implemented here may be useful in the simultaneous study of classical neuroleptics desirable and undesirable CNS effects. PMID- 1745716 TI - Assessment of ethanol's hedonic effects in mice selectively bred for sensitivity to ethanol-induced hypothermia. AB - Mice selectively bred for sensitivity (COLD) or insensitivity (HOT) to the hypothermic effect of ethanol were tested in three tasks purported to assess ethanol's hedonic properties: place conditioning, taste conditioning, and ethanol drinking. In the place conditioning task, distinctive tactile (floor) stimuli were differentially paired with injection of ethanol (2.25 g/kg) or saline, and preference for the tactile stimuli was assessed during a choice test without ethanol. In the taste conditioning task, fluid-deprived mice were given repeated access to saccharin followed by injection of ethanol (2.25 g/kg). In the drinking task, mice were given access on alternate days to a single drinking tube containing water or ethanol in a concentration that gradually increased from 1 to 12% (v/v) over days. HOT mice showed greater conditioned preference for ethanol paired flavor cues, and greater aversion for ethanol-paired flavor cues, and drank less ethanol at concentrations above 5% than COLD mice. HOT mice also showed higher levels of ethanol-stimulated activity than COLD mice. Control experiments indicated that the lines did not differ in initial preference for the tactile and flavor stimuli used in the conditioning tasks. Because the same line differences were seen in mice selected from two genetically independent populations, these studies offer strong evidence of genetic correlations between ethanol's thermal effect and its effect on activity, place conditioning and taste conditioning. Evidence of a genetic correlation between ethanol's thermal effect and ethanol drinking, however, is weaker since it is based on a line difference observed in only one of the genetic replicates. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745718 TI - A model of cardiovascular activation components for studies using autonomic receptor antagonists. AB - Alpha-adrenergic, beta-adrenergic, and cholinergic responses are often considered important activation components when conceptual and empirical analyses are made of single physiological variables and of patterns of cardiovascular reactivity; these autonomic distinctions are also of particular significance in autonomic blockade studies. A Model of Cardiovascular Activation Components is introduced that relates these components to both the measured cardiovascular variables and the protocol of autonomic blockade studies. It is pointed out that a restricted form of the complete model is often implicitly used in cardiovascular psychophysiology. The differential consequences of an erroneous employment of the restricted model are discussed for single and dual blockade protocols. Critical evaluations of autonomic blockade as a tool in cardiovascular psychophysiology are examined and are proposed to be often the consequence of the restricted model assumptions. Lastly, the utility of the Activation Components Model for a componential description of tasks and for componential intertask relationships is illustrated with data from the literature. PMID- 1745719 TI - Behavioral modulation patterns fit an animal model of vagus-cardiac pacemaker interactions. AB - The present study used a computer model of the dynamic interaction between the vagus nerve and the sinoatrial pacemaker membrane potential in the heart of the rabbit to reconstruct heart rate changes under vagal excitation conditions. We asked whether a hypothetical pattern of vagal acetylcholine (ACh) release, which was based on human heart rate results in a reaction time task, could be fit to this model. The reconstructed heart rate results showed changes that were highly consistent with experimental human heart rate changes. The model reliably reproduced effects of parameters such as intrinsic heart rate level, ACh stimulus intensity, and ACh stimulus duration. In addition, the effects of anticipatory vagal ACh release, stimulus-induced ACh, and subsequent blocking of ACh, which usually interact in human cardiac cycle time functions, could be untangled in the reconstructed heart rate results. We concluded that the mathematical model may be useful for formulating hypotheses and constructing experimental task designs for studies of human heart rate. PMID- 1745720 TI - The relationship between menstrual phase and the P3 component of ERPs. AB - Event-related potentials (ERPs) and behavioral ratings were collected from 30 female subjects who were exposed to picture slides. The slides belonged to five affective categories whose content was babies, dermatological cases, ordinary people, male models, and female models. Based on the day of testing relative to their menstrual cycle, the subjects were grouped according to their expected levels of androgens, estrogen, or progesterone. The data were examined to determine whether any ERP component or behavioral rating (non-erotic/erotic, unpleasant/pleasant, simple/complex, and low arousal/high arousal) varied as a function of subjects' hormone defined menstrual phase. Only the P3 component was sensitive to menstrual phase. The P3 to babies and male models was largest when progesterone levels were high. High progesterone was also associated with a decrease in the complexity and eroticism of all slide categories. An increase in the pleasantness of all categories was evident when estrogen levels were high. The results are interpreted as support for an "adaptive context updating" theory of the P3 component of ERPs. PMID- 1745721 TI - The relationship between skin conductance orienting and the allocation of processing resources. AB - Information processing models of autonomic orienting suggest that the elicitation of an orienting response is associated with either the call for, or the actual allocation of, limited attentional processing resources. However, Dawson, Filion, and Schell (1989) reported a directional dissociation between elicitation of the skin conductance orienting response and resource allocation, as indexed by reaction time slowing on a secondary task. Although larger skin conductance responses were elicited by a task-relevant stimulus than by a task-irrelevant stimulus, reaction time showed the opposite pattern (i.e., greater slowing to secondary task probes presented shortly following the onset of the task irrelevant stimulus). In the present report, we describe three experiments which examine the generality of this dissociation effect and test specific hypotheses regarding its nature. Results of the first two experiments revealed that the dissociation effect is observed reliably when the task-relevant and task irrelevant stimuli consist of left ear and right ear tones or high and low pitched binaural tones, across a range of secondary task probe presentation times. However, the third experiment demonstrated that when task-relevant and task-irrelevant stimuli are presented to different sensory modalities (auditory and visual), orienting and resource allocation are both greater during the task relevant than the task-irrelevant stimuli, thus eliminating the dissociation effect. These results support the hypothesis that the dissociation effect is due to a switch of attention initiated because of the physical similarity of the task relevant and task-irrelevant stimuli, and suggest that there is a fundamentally positive relationship between skin conductance orienting and resource allocation under selective attention conditions. PMID- 1745722 TI - Task versus component consistency in the development of automatic processing: a psychophysiological assessment. AB - A study was conducted to examine the role of consistency in the development of automatic processing. Subjects performed a memory search task in which consistent and inconsistent attending and responding were factorially combined. The task was performed with memory set sizes of two and four items. Results indicated that automaticity developed with consistent attending regardless of whether responding was consistent or inconsistent. However, measures of reaction time, P300 latency, and P300 amplitude revealed costs for inconsistent responding that were attributed to both stimulus evaluation and response related processes. The results suggest that total task consistency is not necessary for the development of automatic processing. Instead, it appears that automaticity can develop for consistent task components even when stimulus-response consistency is not maintained across the entire task. PMID- 1745723 TI - Haemodynamic adjustments to mental stress in normotensives and subjects with mildly elevated blood pressure. AB - Cardiac output, heart rate, stroke volume, pre-ejection period, total peripheral resistance, systolic and diastolic blood pressure, and oxygen consumption were monitored or derived in young men with mildly elevated casual blood pressures and unambiguously normotensive control subjects before, during, and after exposure to a mental arithmetic stress. Measurements were also taken while subjects underwent graded dynamic exercise. This permitted cardiac output-oxygen consumption regression equations to be calculated and, as a consequence, cardiac output during mental stress to be represented as additional cardiac output. Systolic and diastolic blood pressure were higher during all phases of the study in the mildly elevated blood pressure group. An overall groups effect during the mental stress phase of the experiment was observed for cardiac output and pre-ejection period, and the effect for stroke volume was close to significance. Significant Groups X Periods interactions were found for cardiac output and additional cardiac output, and the heart rate effect was nearly significant. Post-hoc comparisons here indicated that, in the main, group differences in these cardiac variables were more evident during the mental arithmetic stress than during the pre- and post task baseline periods. Total peripheral resistance did not differ reliably between groups and the cardiac effects were specific to the mental stress phase of the study. PMID- 1745724 TI - Children's cardiovascular reactivity: stability of racial differences and relation to subsequent blood pressure over a one-year period. AB - After measuring blood pressure and heart rate at rest and during a video game procedure in 477 children enrolled in 3rd grade, 434 (91%) children had these measurements repeated a year later in 4th grade. Black children demonstrated greater blood pressure and heart rate reactivity than White children in both years, and an increase in heart rate reactivity from 3rd to 4th grade. Gender effects were inconsistent. Systolic and diastolic blood pressures during the video game were more highly correlated from year-to-year than were the resting measures. Regression analysis indicated that systolic reactivity was significantly related to subsequent systolic pressure at rest, particularly among Black girls. Diastolic reactivity was associated with subsequent resting diastolic pressure only among White children. Associations between reactivity and future blood pressure were independent of initial resting blood pressure. This study suggests that cardiovascular reactivity to psychological stress may be one important factor in future level of blood pressure and that the increased heart rate reactivity of Black children may be associated with the prevalence of hypertension among Black adults. PMID- 1745725 TI - Temperature, time-of-night of testing, and responsiveness to stimuli presented while sleeping. AB - The present study examined how time-of-night of testing and body temperature related to responsiveness to stimuli presented in sleep. Nine males slept for two nonconsecutive nights in the sleep laboratory. On Night 1, tympanic temperature was assessed at 30-min intervals. On Night 2, responsiveness was assessed with an incremental series of tones (5dB steps) presented in sleep stages 2, 3/4, and REM throughout the night (0030-0800 h). Subjects were instructed and given practice prior to sleep to make a microswitch closure to the tones. Results showed a curvilinear pattern of responsiveness across the night in that the intensity of tones required for a response increased until about 0530 h, then decreased thereafter. This pattern of responsiveness was positively related to the circadian rhythm of body temperature. A close correspondence was also found between the temperature trough and the performance trough (both occurred at about 0530 h). A greater emphasis on circadian factors may help understand previously reported but contradictory findings. The present results also suggest that measures of responsiveness follow a circadian pattern regardless of the sleep/wake state. PMID- 1745726 TI - The waltzing oddball. AB - We investigated whether task relevance and probability interact to influence P3 amplitude. High and low tones were presented in random order with equal probability. In the control condition (standard oddball), every high tone had to be counted. In the waltz condition, high tones had to be counted only if they were preceded by two other high tones. It was predicted that the P3s evoked by targets in the waltz condition would be larger than the P3s evoked by the same sequence of targets in the oddball condition. That is, the frequency of occurrence of the targets should have an effect on P3, in addition to effects of the frequency of stimulus occurrence and stimulus task relevance (target/nontarget). This prediction was upheld. However, the largest P3s were evoked by nontargets following two high tones in the waltz condition. These P3s had a more anterior topographic maximum than usual. We contend that these anterior P3s reflect the interruption of an ongoing task and cannot be easily fit into the framework of the two concepts of task relevance and probability. PMID- 1745727 TI - Mismatch negativity outside strong attentional focus: a commentary on Woldorff et al. (1991) AB - Several previous papers have suggested that the mismatch negativity (MMN), an event-related potential (ERP) component specific to stimulus change after repetition, is fully automatic, that is, not affected by attention. Woldorff, Hackley, and Hillyard (1991), however, report that the MMN elicited by an intensity decrement of a repeating stimulus is considerably attenuated when attention is strongly focused on other stimuli. The present commentary attributes most of this effect to attention effects on ERP components other than the MMN but also admits that some attentional reduction of the MMN component indeed occurred. This attenuation was interpreted by Woldorff et al. as indicating suppression of early sensory processing in unattended channels, but this is contraindicated by some very recent data from the present author's laboratory and elsewhere showing that the MMN to frequency change is not attenuated outside a strong attentional focus. Consequently, an alternative explanation is proposed for Woldorff et al.'s important finding. PMID- 1745728 TI - Parasites and sexual selection: a macroevolutionary perspective. AB - The Hamilton-Zuk hypothesis postulates a causal link between parasitism and the evolution of epigamic traits by intersexual selection. Oversimplified assumptions about basic parasite biology, ambiguous formulation of the hypothesis, and poor communication between ethologists and parasitologists have hampered its testing. The hypothesis is supported at the microevolutionary level if females show significant preference for lightly or uninfected males, if intensity of infection reflects host resistance to parasites that depress host fitness by causing disease, and if intensity of infection is related to the degree of epigamic development. It must be shown that particular parasites cause disease, that the host population is polymorphic for resistance to infection by those species, and that female hosts are capable of distinguishing male hosts with low parasite loads due to heritable aspects of host resistance from males that are uninfected due to chance. The macroevolutionary prediction of the hypothesis, that species displaying strongly developed epigamic characters should host "more parasites" than species with weakly developed epigamic traits, contradicts the microevolutionary dynamic of the hypothesis, and is too ambiguous. We propose a macroevolutionary prediction based on understanding the evolutionary origin of epigamic traits and the evolutionary origin of each host-parasite association. Associations originating in the ancestor in which the epigamic trait appeared corroborate the hypothesis most strongly; those originating prior to the evolution of the epigamic trait corroborate it weakly; those beginning after the origin of the epigamic trait could not have been involved in the origin and spread of the epigamic trait. PMID- 1745729 TI - Ecological frames of mind: the role of cognition in behavioral ecology. AB - Cognitive psychology is the study of how information, from the senses and from memory, is used in the production of behavior. Investigation of the specifics of behavioral adaptation has already led some behavioral ecologists into the domain of animal cognition. I make several arguments for the benefits and the necessity of a sophisticated assessment by ecologists of the cognitive aspects of behavioral adaptation. First, because cognition typically serves to produce adaptive behavior, cognitive structure and function should reflect ecological demands; studies of cognition in ecological contexts are opportunities to understand adaptation. Furthermore, constraints on cognitive properties may help determine how behavior meets the environment. Studies of spatial memory in food caching corvids exemplify how cognitive aspects of behavior may both reflect and determine specifics of adaptation. Second, many models in behavioral ecology assume certain cognitive abilities, such as timing or counting. Cognitive theory and methodology should be used to determine whether animals possess these abilities. I have provided examples. Third, consideration of cognitive function can lead to original ideas about the details of behavioral adaptation. Without a thorough integration of cognitive psychology with behavioral ecology, our understanding of the relation between behavior and selective pressures will be compromised. PMID- 1745730 TI - [Allergic reactions in dental practice--clinical and therapeutic recommendations]. PMID- 1745731 TI - [Probond--proven easy technique in crown and bridge prosthetics. 1. Principles and preparation results]. PMID- 1745732 TI - [Causal contribution to the question of repairability of synthetic resins]. PMID- 1745733 TI - [Vital microscopical study of microcirculation in dental pulp]. PMID- 1745734 TI - [Galvano-outer telescope by direct technique]. PMID- 1745735 TI - [Orthodontic and oral surgical treatment planning by computer, for example, the Dentofacial Planners (1)]. PMID- 1745736 TI - [Interpretation of radiographs]. PMID- 1745737 TI - [ABC of practice management: K-communication]. PMID- 1745738 TI - [Clinical and microbiological findings, that can cause failure of dental implants]. PMID- 1745739 TI - [Edema therapy in dental interventions with hydrolytic enzymes]. PMID- 1745740 TI - [Clinical investigation of a posterior composite materials after 5 and 8 years]. PMID- 1745741 TI - [Prosthetic construction principles in periodontally reduced dentition]. PMID- 1745742 TI - [Joint oriented arrangement of maxilla with "Condyle-Positioning apparatus" in frame of orthodontic surgery]. PMID- 1745743 TI - [Apically placed flaps for treatment of advanced cases of marginal periodontitis- case example (1)]. PMID- 1745745 TI - [ABC of practice management: P-patient oriented practice]. PMID- 1745744 TI - [Interpretation of radiographs]. PMID- 1745746 TI - [Psychophysiological stress and requirements in dental practice]. PMID- 1745747 TI - [Kindergarten--an institution for group prophylaxis]. PMID- 1745748 TI - [Mercury content of saliva]. PMID- 1745749 TI - [The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 1. The experimental model. The radiation loads on animals kept continuously under external and internal radiation exposure in the area of the Chernobyl Atomic Electric Power Station]. AB - Irradiation conditions in which laboratory animals were kept in experimental laboratories of Chernobyl and Kiev after the accident at the Chernobyl A.P.S. are described. The data are presented on the spectral structural and activity of radionuclides in the diet as well as in the organs and tissues of the animals. The radiation loads have been estimated with regard to an external gamma component and the internal one contributed by the incorporated radionuclides. It has been shown that radiation doses received by the animals during their lifetime due to these contributions do not exceed units of cGy. PMID- 1745750 TI - [The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 2. The state of bone marrow hematopoiesis in rats]. AB - It has been shown that rats born during the first months after the Chernobyl A.P.S. disaster exhibit essential changes in the peripheral blood and bone marrow haemopoiesis throughout the entire lifetime. Rats brought up in Chernobyl from the age of three months on display even more pronounced changes. It is assumed that the changes in the haemopoiesis develop due to the continuous influence of low-level radiation of different quality and are attributed to the effect of the incorporated radionuclides. PMID- 1745751 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 3. The morphological and ultrastructural changes in the lungs of rats]. AB - The morphological and ultrastructural changes revealed in the lungs of rats kept within the Chernobyl accident zone during the period of 6 to 24 months were shown to be uniform and multicomponent. The changes were found both in the respiratory and the vascular connective tissue. The inflammatory processes occurred with formation of pneumonic foci, hypo- and disatelectasis, emphysematous changes, impairment of interalveolar septa, and connective tissue cell proliferation. In the lung tissue, focal and diffuse lymphoid proliferates and, at later stages, lymphomatous changes were revealed. PMID- 1745752 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 5. Longevity and the carcinogenic effects]. AB - Remote effects in laboratory animals living in conditions of exposure to a mixture of external and internal radiation resulted from the Chernobyl A.P.S. disaster have been investigated. It has been found that the rate of deaths from non-tumor illnesses grows, the incidence of neoplasms increases and their latency time decreases. The redistribution within the spectrum of benign and malignant tumors and the increase in the multiplicity coefficient have been revealed. It is concluded that chronic exposure of animals to low-level radiation from the radionuclides, resulted from the accident, brings about a much larger number of negative stochastic and nonstochastic remote effects as compared to those expected from the extrapolation of the effects produced by high radiation doses. PMID- 1745753 TI - [The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 6. The physiological development and cytogenetic indices of the progeny of rats]. AB - Certain alterations have been revealed in the postnatal ontogenesis parameters of albino mongrel rats and their descendants constantly kept within the thirty kilometer zone of the Chernobyl A.P.S. Structural disturbances have been found in bone marrow cell chromosomes. PMID- 1745754 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 7. The content of lipid peroxidation products and free fatty acids and the catalase activity in a number of organs and tissues of rats]. AB - The content of malonic dialdehyde, dienic conjugates and free fatty acids, and catalase activity were determined in some organs and tissues of chronically irradiated rats. Certain regularities were found in lipid metabolism changes. The MIGI-K preparation was shown to normalize some indices under study. PMID- 1745755 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 8. The status of cellular immunity in different generations of rats]. AB - In studying immunity in laboratory rats of different generations (P, F1 and F2) brought up in Chernobyl in 1989-1990 the authors have revealed the development of leuko- and lymphopenia; decrease in the absolute content of immunocompetent cells bearing Fc receptors to IgG; stable and long-lasting suppression of blood NK cell activity; reduction of antibody-dependent cytotoxicity; and changed ability of blood lymphocytes to interact contactly with allogenic mast cells. The most considerable disorders have been found in 6- and 9-month-old F1 rats and in 3- and 6-month-old F2 rats. PMID- 1745756 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 9. The morphofunctional indices of the immunocompetent organs in mice]. AB - The permanent action of small doses of low-intensity radiation on the immune status of 2.5-3.5 month CC57W mice has been investigated. Total doses of internal and external irradiation were about few cGy. The permanent action of low-level radiation on the experimental animals of the first and fourth generations was shown to change spleen and lymph nodes weights and the count of lymphocytes isolated from these organs. Cellularity and DNA synthesis in the lymph-node lymphocytes and their proliferative response to polyclonal mitogens also changed. The alterations in the parameters that characterized T-lymphocyte population were statistically significant. PMID- 1745757 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 10. Cooperative immune reactions in different generations of mice]. AB - The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and "graft versus host" disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antiviral antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms. PMID- 1745758 TI - [The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 11. The ultrastructure of the bone marrow cells in different generations of rats]. AB - In studying the bone marrow cell ultrastructure in male rats (F0-F2 generations) aged 3 months, which were brought up within the thirty kilometer Chernobyl A.P.S. disaster area, considerable submicroscopic changes have been revealed in the cells at all stages of maturation, including undifferentiated blasts and mature forms of cells of the neutrophilic, eosinophilic, monocytic and erythroid haemopoiesis series, as well as stromal elements of the microenvironment, megakaryocytes and endothelium. The severity of these changes increases, as the number of generations grows, displaying frequently a destructive character. PMID- 1745759 TI - [The effect of the accident at the Chernobyl Atomic Electric Power Station in 1986 on the fish population of a cooling pond]. AB - The cytogenetic analysis of Cyprinus carpio eyes, developing Blicca bjoerkna L. eggs, and eggs and larvae of Hypophtalmichthys molitrix Val. has demonstrated that the yield of cells with chromosome aberrations in the fish species under study is normal, while the level of variability of morphometric indices in offspring is considerably higher than that in parent fish. PMID- 1745760 TI - [Micronucleus formation in the bone marrow cells of chronically irradiated mice with subsequent acute gamma irradiation]. AB - With the use of the micronuclear test method it has been shown that mice preirradiated with gamma rays at a low dose rate exhibit a decreased frequency of chromosome aberrations induced in bone marrow cells by subsequent acute exposure to gamma radiation as compared to mice not subjected to preliminary irradiation. Such animals have a higher radioresistance with respect to the survival rate. The results obtained suggest the possibility of induction by ionizing radiation, at a low dose rate, of adaptive repair response at the organism level. PMID- 1745761 TI - [The enhanced radioresistance (adaptive response) in vivo of splenic colony forming units (CFU-S) following the exposure of mice to 60Co gamma rays at low doses]. AB - An increase of resistance to radiation damage of human lymphocytes previously exposed to low doses of ionizing radiation from incorporated tritiated thymidine was observed by G. Olivieri et al. in 1984. The phenomenon was named adaptive response and its occurrence was reported by others for many animal and plant cells. In this research we studied the adaptive response of spleen colony formation at different time after previous irradiation of mice with low doses of 60Co gamma rays. Our results suggest that the pretreatments protect spleen colony formatting units (CFU-S) from the second damaging radiation dose of 1.5 Gy during long time (as many as one month). PMID- 1745762 TI - [The phenomenon of adaptive immunity in exposure to nonionizing microwave radiation]. AB - In experiments with albino rats exposed to microwaves (500 microW/cm2), a model of adaptive immunity was developed by transferring lymphoid cells of exposed animals. The effect of microwave radiation was shown to cause autoimmune disorders that were displayed against the background of the structural and functional disturbances of the hematoencephalic barrier. PMID- 1745763 TI - [DNA damages in individual mammalian cells]. AB - The method of alkaline microelectrophoresis of nucleoid DNA of isolated cells built in an agar gel was used to study the harmful effect of radiation on the genome of mouse peripheral blood lymphocytes. The yield of the lymphocyte DNA structure damages in irradiated animals and in the in vitro exposed lymphocytes was a linear function of radiation dose within the dose range from 0.5 to 5 Gy and 0.27 to 1 Gy respectively. A study was made of the dynamics of DNA structure damages in cells NIH 3T3 exposed to 3 Gy radiation, and in mouse lymphocytes exposed to 4 Gy radiation. PMID- 1745764 TI - [The effect of low doses of external gamma irradiation on the chromatin structure and activity of the histone-specific proteinases of rat brain cells]. AB - Irradiation of rats with doses of 0.5 to 2 Gy was shown to cause dose-dependent changes in the sensitivity of brain cell chromatin to the effect of DNAase I that were manifested by the increased level of DNA hydrolysis and a high content of the chromatin soluble fractions. The chromatin structure was only partially restored 24 h after irradiation. Changes in the chromatin structure were accompanied by the increase in the histone-specific proteinase activity. PMID- 1745765 TI - [The content of cyclic nucleotides, free cytoplasmic Ca2+ and malondialdehyde in the splenic lymphocytes and thymocytes of rats under the action of moderate doses of radiation]. AB - It has been shown that the malonic dialdehyde (MDA) content in spleen lymphocytes of rats increases after whole-body X irradiation with a dose of 0.5 Gy to reach the maximum level in 24 h. Simultaneously, the concentration of cGMP and free cytosol Ca2+ increases. With a dose of 1 Gy MDA content of cells increases 6 h following irradiation. The maximum drop of the release of viable lymphocytes from the spleen and thymus, observed 24 h and 3 days after irradiation respectively, coincides with the appearance of the second peak of the MDA content. The level of cGMP remains decreased throughout the period of about 6 days. The onset of lymphocyte repopulation in the spleen on day 6 coincides with the decrease in the MDA level and increase in the cytosol Ca2+ concentration. PMID- 1745766 TI - [The effect of chronic gamma irradiation in small doses on the adenylate cyclase activity of lung tissue plasma membranes in rats]. AB - A study was made of the response of adenylate cyclase of cytoplasmic membranes of pulmonary tissue to chronic gamma irradiation of rats at a low-dose rate (0.036 cGy/day). The adenylate cyclase complex receptors were shown to respond to such exposure by activation of the enzyme they control and by being more sensitive to their specific effector, isoproterenol. The role of receptors in the manifestation of radiation hormesis is discussed. PMID- 1745767 TI - [The mechanisms determining the course and outcome of the exposure of the body to ionizing radiation]. PMID- 1745768 TI - [The way to molecular cell genetics]. PMID- 1745769 TI - [Cultured cell lines--materials for molecular cell genetics]. PMID- 1745770 TI - [Human cells in culture--aging and immortalization]. PMID- 1745771 TI - [Human hereditary diseases]. PMID- 1745772 TI - [Cancer cells and carcinogenesis]. PMID- 1745773 TI - [Embryonic stem cell, early development and cell differentiation]. PMID- 1745774 TI - [DNA replication and DNA repair]. PMID- 1745775 TI - [Analysis of the cell cycle]. PMID- 1745776 TI - [Genetic marker of somatic cell]. PMID- 1745777 TI - [Genetic analysis of somatic cells]. PMID- 1745778 TI - [Genetic recombination in somatic cells]. PMID- 1745779 TI - [Experiment for lyonization and genomic imprinting]. PMID- 1745780 TI - [Fundamentals of cell cultivation]. PMID- 1745781 TI - [Establishment of cell strains]. PMID- 1745782 TI - [Preparation of synchronized cells]. PMID- 1745783 TI - [Frequency and induction of mutation]. PMID- 1745784 TI - [Concentration and specific selection of mutants]. PMID- 1745785 TI - [Isolation of mutant cells by a replica method]. PMID- 1745786 TI - [Isolation of temperature-sensitive mutant cells]. PMID- 1745787 TI - [Isolation of mutant cells requiring various nutrients]. PMID- 1745788 TI - [Isolation of drug-resistant mutant cells]. PMID- 1745789 TI - [Isolation of mutant cells sensitive to radiation or similar physical agents]. PMID- 1745790 TI - [Isolation of mutant cells for the studies of cell architecture, biological transport, and cellular responses]. PMID- 1745791 TI - [Complementation test]. PMID- 1745792 TI - [Analysis of reverse mutant cells]. PMID- 1745793 TI - [methods for gene transfer]. PMID- 1745795 TI - [Gene targeting]. PMID- 1745794 TI - [Transfer and recovery of genes]. PMID- 1745796 TI - [Preparation of chromosomal panels and chromosome mapping]. PMID- 1745797 TI - [Detection of chromosomal aberrations]. PMID- 1745798 TI - [Analysis of mitochondrial DNA as plasmagene]. PMID- 1745799 TI - [Anorexia nervosa: current considerations]. PMID- 1745800 TI - [Sarcoidosis. Retrospective study of 30 cases in Salamanca and comparison with other national series]. AB - Sarcoidosis is a disease which presents important clinical differences according to its geographical distribution. Thus, the objective of this study was to evaluate the epidemiologic, clinical, radiologic, and diagnostic characteristics in a series of 30 sarcoidosis patients in the province of Salamanca (representing the Castilla-Leon region). The most relevant results are the following: a) in our region, sarcoidosis predominates in females and furthermore, the presenting age in females is greater than in males; b) there is a clear predominance of the disease in the rural area; c) the prevalence of smoking habit in these patients is low (10%); d) the clinical manifestations are similar to other Spanish series with the exception, however of a high incidence of hypercalciuria; e) there is no correlation between the increase in sedimentation rate and the degree of sarcoidosis activity; f) there is a predominance of the radiologic type 11 of the disease and there is a high number of atypic radiologic patterns. The results obtained are with regard to the pathogeny are discussed as well as the differences and similarities of this series with other preceding from other regions. PMID- 1745801 TI - [Uric acid calculi: infrequent cause of acute renal failure]. AB - We reviewed the clinical histories of 14 patients diagnosed of acute obstructive renal failure due to bilateral or unilateral uric calculi in patients with only one functioning kidney for a period of 14 years (1974-1987). Urine was alkalinized in all patients. The increase in urine pH was effective in resolving the obstruction in 12 patients. The alkalinizing methods which succeeded in permeabilizing the urinary tract, considering each functioning kidney independently were: intravenous in 5/21, upstream urethral catheterism in 9/21 and by nephrostomy catheter in 5/21. Surgery was performed in 2 patients. In the later the calculi were of double composition. The most frequent complications were: urinary infection in 7/14 patients, chronic renal failure in 4/14 patients, sepsis in 3/14 patients and bacteremia in 2/14 patients. None of the patients died. PMID- 1745802 TI - [Use of DNA probes labelled with radioisotopes in the mycobacteria laboratory]. AB - We have studied 540 mycobacterial strains isolated in Lowestein-Jensen medium and 133 samples of different pathologic products against commercialized 125I-DNA Mycobacterium tuberculosis complex, Mycobacterium avitum-intracellulare and Mycobacterium gordonae. The sensitivity, specificity and positive and negative predictive values against isolated strains was 100% for the 3 studied probes. The 125I-DNA probe specific for M. tuberculosis complex is studied in samples with positive bacciloscopy; statistic values vary according to the cutting point of the different percentages of hybridization: at 1.5% the sensitivity, specificity and predictive negative and positive values are 38.6%, 71.4%, 97.5%, and 9.4% respectively, while if the cutting point percentage is 3% these values are: 33.1%, 100%, 100%, and 7.8% respectively. We believe that with these probes the identification time is limited to time needed for the incubation of prime cultures, and in some cases it can be performed on the day the samples reach the laboratory. PMID- 1745803 TI - [Pattern of plasma lipids and insulin blood levels in male patients with non insulin-dependent diabetes mellitus and moderate obesity]. AB - The goal of the present work is the study of the plasmatic lipid profile in non insulin dependent diabetes mellitus (NIDDM) patients with abdominal obesity (AO), comparing them the NIDDM patients without AO and with OA persons without NIDDM. For that purpose we developed a methodology in which we have studied the body mass index (BMI: kg/m2) the hip-waist index (HWI) (0.95 = AO), lipid parameters, hydrocarbon, titers and serum insulin levels. The results are referred to four groups where we can throw into relief a statistically significant increase in triglycerides and a marked decrease in HDL cholesterol in OA and DM patients when compared to the group with AO without MD or to the group with MD without AO. Based on the results obtained the conclusions can be summarized as follows: The presence of abdominal obesity is a factor that favors the appearance of high levels of serum triglycerides and low levels of HDL-cholesterol in NIDDM. On the other hand, DM is a factor that increases the levels of triglycerides with low levels of HDL-cholesterol which already exist in AO. PMID- 1745804 TI - [Post-traumatic hemoperitoneum: a rare complication of peritoneal splenosis]. AB - Peritoneal splenosis is a frequent condition after traumatic spleen fracture, which, given that it is usually asymptomatic, is often not diagnosed unless a laparotomy is performed for some other reason. The case is presented of a 9 year old boy splenectomized a few years earlier because of traumatism, who again suffers abdominal injury with the development of hemoperitoneum, observing during surgery multiple splenosis foci disseminated all over the abdominal cavity, some of which present rupture and hemorrhage, constituting the cause of hemoperitoneum. PMID- 1745805 TI - [Late recurrence in pheochromocytoma: need for a long term follow up]. AB - Pheochromocytoma is a catecholamine secreting tumor which has been traditionally considered as a potentially curable cause of hypertension. However, the existence of malignant pheochromocytomas as well as the problem which the recurrence of benign pheochromocytomas present, make the eradication of this tumor more complicated. It is note worthy the difficulty in localizing recurrent pheochromocytomas as well as the prognostic interest that presents the possibility of differentiating between recurrence and metastasis. We refer the case of a female patient suffering benign adrenal pheochromocytoma, who, 10 years it was surgically removed, presented a relapse of symptoms, and was diagnosed of extra-adrenal pheochromocytoma, in Zuckerkandl organ. The importance of performing a long term post-surgical follow-up in these patients is stressed. PMID- 1745806 TI - [Granular cell laryngeal tumor]. AB - Granular cell tumor is a rare benign tumor which when affects the larynx, it characteristically affects the vocal cords, causing dysphonia as the main clinical manifestation. The term granular cell myoblastoma proposed and extensively used seems to be inadequate since all the observations suggest its origin in Schwann cells, with no relation to muscle cells. Although the existence of malignant granular cell tumors has been reported, the vast majority show a benign behaviour, reaching its cure after complete surgical removal of the lesion. PMID- 1745807 TI - [Primary hyperparathyroidism: pathogenic and therapeutic dilemmas]. PMID- 1745808 TI - [54-year-old man with headache, nasal obstruction and cranial nerve involvement]. PMID- 1745809 TI - [Pancreatic cystadenoma during gestation]. PMID- 1745810 TI - [Septic lesions due to Escherichia coli]. PMID- 1745811 TI - [Severe hypercalcemia in adolescence: a rare presentation of primary hyperparathyroidism]. PMID- 1745812 TI - [Epidermal growth factor behavior in breast cyst fluid. Differences as a function of the three existing types]. PMID- 1745813 TI - [Pleural tuberculosis]. PMID- 1745814 TI - [Benign parotid lymphoepithelial cyst in a patient with HIV infection]. PMID- 1745815 TI - [Amenorrhea secondary to obesity]. PMID- 1745816 TI - [Solitary cranial metastasis as an initial manifestation of renal carcinoma]. PMID- 1745817 TI - [Spontaneous pneumomediastinum as a complication of a sports competition]. PMID- 1745818 TI - Molecular mechanism of action of a steroid hormone receptor. PMID- 1745819 TI - Gonadotropin-releasing hormone pulses: regulators of gonadotropin synthesis and ovulatory cycles. AB - The data reviewed present evidence that the pattern of GnRH secretion is an important factor in the regulation of gonadotropin subunit gene expression, gonadotropin synthesis, and secretion. The information on regulation of mRNA expression by GnRH pulses should be considered with some caution, as the experiments were performed in male rats and may not accurately reflect events in female primates or humans. However, an overall pattern emerges which suggests that common factors may be involved in all mammalian species. If current evidence is correct, and only a single gonadotropin-releasing hormone exists, then mechanisms to differentially regulate the three gonadotropin genes may involve changes in GnRH secretion. Alterations in GnRH pulse frequency and amplitude are recognized by the pituitary gonadotrope cell and could be the mechanism used to effect differential expression of the gonadotropin subunit genes. Differential regulation of subunit gene expression would be expected to be critically important in the establishment of pubertal maturation, and subsequently in the maintenance of ovulatory cycles in women. Our hypotheses, proposing a major role of pulsatile GnRH secretion in the regulation of human reproduction, are summarized in schematic form in Fig. 14 for men and Fig. 15 for women. In utero and during the first few months of life, GnRH is secreted at a relatively fast frequency (approximately 1 pulse/hour). During the first year, GnRH secretion is inhibited and both the amplitude and apparent frequency of pulsatile release is markedly reduced. The mechanisms involved in inhibiting GnRH release remain unclear in humans. Similarly, the mechanisms involved in the disinhibition of GnRH secretion, which first occurs during sleep at the initiation of puberty, are unclear, but in humans do not appear to involve opiates. In males, the increased frequency and amplitude of GnRH secretion favor LH synthesis and release, which in turn stimulates testosterone secretion (Fig. 14). Testosterone acts at the hypothalamus, perhaps through opioid mechanisms, to inhibit GnRH pulse frequency and to maintain a regular pattern of pulses occurring approximately every 90-110 min in adult males. In females, the mechanisms involving alterations in the patterns of GnRH secretion to regulate reproduction appear more complex. This may reflect the need to differentially synthesize and secrete FSH and LH at different times during reproductive cycles to allow orderly follicular maturation and ovulation. As shown in Fig. 15, we hypothesize that the events during the first decade of life and through the initiation of nocturnal GnRH secretion at puberty are similar in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745820 TI - Steroids, receptors, and response elements: the limits of signal specificity. PMID- 1745821 TI - Molecular biology of human renin and its gene. AB - This article describes investigations of several aspects of the molecular biology of the human renin gene and the three-dimensional structure of renin and its precursor, prorenin. Because of the importance of the RAS in hypertension, heart failure, renal failure, and possibly other disorders such as atherosclerosis, it is critical to understand the detailed control of this system. This control involves regulation at the transcriptional level, folding of prorenin, sorting of prorenin to a regulated pathway where it is proteolytically cleaved to renin and released in response to secretogogues, constitutive release of uncleaved prorenin, and nonproteolytic activation of prorenin. Currently there is great interest not only in the control of renin in the kidney, the sole source of circulating renin, but also at extrarenal sites where RAS activity may regulate cardiovascular functions. The renin gene was found to be expressed significantly in the renal juxtaglomerular cells and several other cell types. Most tissue culture cells did not express the gene; exceptions were cultured SK-LMS-1 cells and cAMP-stimulated human lung fibroblasts. Cultured human uterine-placental cells expressed the human renin gene at levels higher than in other cell types assessed. Renin mRNA had the same start site in the placental cells as the kidney and was regulated by calcium ionophores and cAMP. Thus, these cells provide primary nontransformed human cells to study the homologous human promoter. Transfected renin promoters showed cell type-specific expression and cAMP responsiveness in these cells in constructs containing as few as 102 bp of 5' flanking DNA. DNA upstream from this appears to contain an inhibitory element(s) that may have some tissue specificity in its distribution. The cAMP response is not due to cAMP induction of a transcription factor that secondarily affects the renin promoter. A novel element may be involved, since the promoter does not contain a CRE element that mediates many cAMP responses, and the cells do not appear to respond to another known cAMP-responsive transcription factor, AP-2. Studies with transfected vectors expressing a mutant cAMP-responsive protein kinase A regulatory subunit suggest that cAMP is not responsible for basal renin promoter activity in the placental cells. By contrast, cAMP induces in essence gene activation in WI26VA4 transformed human lung fibroblasts in which renin mRNA levels increase by up to 150-fold in response to forskolin. Thus, cAMP may activate renin gene expression under certain circumstances and tissue-specific renin gene expression may be directed by more than one mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745822 TI - Cellular and molecular analysis of pancreatic islet cell lineage and differentiation. PMID- 1745823 TI - Neuroendocrine control of human reproduction in the male. AB - The traditional difficulty in studying the neuroendocrine control of reproduction in the human male has been the inability to tease out the hypothalamic from the pituitary component of this neuroendocrine system. The use of multiple models, each with its own strength and weakness, represents an overlapping approach that has permitted further insights to be gained into the hypothalamic control of the neuroendocrine regulation of gonadotropin secretion in the human. Such an insight is an important prerequisite to the understanding of the pathophysiology of various disease states, the unraveling of a control of FSH secretion by GnRH vs other modulators, and the subsequent design of rational therapies for male reproductive disorders. PMID- 1745824 TI - Complex hormone response unit regulating transcription of the phosphoenolpyruvate carboxykinase gene: from metabolic pathways to molecular biology. PMID- 1745825 TI - Mammalian glucose transporters: structure and molecular regulation. PMID- 1745826 TI - Immortalization of neuroendocrine cells by targeted oncogenesis. PMID- 1745827 TI - Neuroendocrine regulation of the luteinizing hormone-releasing hormone pulse generator in the rat. AB - We have analyzed the mechanisms by which several known regulators of the LHRH release process may exert their effects. For each, we have attempted to determine how and where the regulatory input is manifest and, according to our working premise, we have attempted to identify factors which specifically regulate the LHRH pulse generator. Of the five regulatory factors examined, we have identified two inputs whose primary locus of action is on the pulse-generating mechanism- one endocrine (gonadal negative feedback), and one synaptic (alpha 1-adrenergic inputs) (see Fig. 29). Other factors which regulate LHRH and LH release appear to do so in different ways. The endogenous opioid peptides, for example, primarily regulate LHRH pulse amplitude (Karahalios and Levine, 1988), a finding that is consistent with the idea that these peptides exert direct postsynaptic or presynaptic inhibition (Drouva et al., 1981). Gonadal steroids exert positive feedback actions which also result in an increase in the amplitude of LHRH release, and this action may be exerted through a combination of cellular mechanisms which culminate in the production of a unique, punctuated set of synaptic signals. Gonadal hormones and neurohormones such as NPY also exert complementary actions at the level of the pituitary gland, by modifying the responsiveness of the pituitary to the stimulatory actions of LHRH. The LHRH neurosecretory system thus appears to be regulated at many levels, and by a variety of neural and endocrine factors. We have found examples of (1) neural regulation of the pulse generator, (2) hormonal regulation of the pulse generator, (3) hormonal regulation of a neural circuit which produces a unique, punctuated synaptic signal, (4) hormonal regulation of pituitary responsiveness to LHRH, and (5) neuropeptidergic regulation of pituitary responsiveness to LHRH. While an attempt has been made to place some of these regulatory inputs into a physiological context, it is certainly recognized that the physiological significance of these mechanisms remains to be clarified. We also stress that these represent only a small subset of the neural and endocrine factors which regulate the secretion or actions of LHRH. A more comprehensive list would also include CRF, GABA, serotonin, and a variety of other important regulators. Through a combination of design and chance, however, we have been able to identify at least one major example of each type of regulatory mechanism. PMID- 1745828 TI - [Clinico-pathological evaluation of patients with homozygous familial hypercholesterolemia]. AB - The authors have studied 8 patients with Homozygous Familial Hypercholesterolemia (FHO) an autosomal genetic dominant disease due to mutation of the gene encoding a cell surface receptor for LDL. Anatomic and pathologic abnormalities caused by LDL-cholesterol and B-Apolipoprotein high plasma levels were found. We also measured malondialdehyde levels in plasma and atherosclerotic plaques of the only autoptic case observed. MDA-levels are an index of lipid peroxidation. Cutaneous xanthomatosis lesions and severe cardiovascular disease were also present. PMID- 1745829 TI - [Hypersensitivity of the carotid sinus in syncope and its diagnostic role: therapeutic implications and follow-up]. AB - Our aim was to assess the incidence and clinical characteristics of carotid sinus hypersensitivity in a group of subjects suffering from syncope. The total number of patients was 118. Twenty-four of them (20%) were diagnosed as epileptics (first attack) and 38 (32%) as vasodepressors. 56 patients with unexplained syncope underwent carotid sinus massage during electrocardiographic registration and pressure monitoring. 41 patients were found to have carotid sinus hypersensitivity. 34 of these 41 patients received implantation of a pacemaker. Abnormal sinus node function was noted in 30, abnormal atrioventricular node function in 3 and combined abnormal sinus node and AV node function in 1. Furthermore three other patients who were negative to massage were implanted with a pacemaker because they had an organic heart disease and recurrent syncope. Different tests as 24-hour monitoring ecg and electrophysiologic study showed no better results in the diagnosis of syncope. Our data demonstrates the diagnostic importance of carotid sinus massage in the diagnosis of syncope. The validity of this method is confirmed by the 24 month follow-up. PMID- 1745830 TI - [24-hour blood pressure: effects of sports in aged subjects]. AB - The present study deals with the blood pressure (BP) and heart rate (HR) 24-h pattern in aged people of both sexes ranging in age from 66 to 75 years. 20 subjects were active in agonistic sports (running and swimming), 20 others had sedentary habits. BP and HR were studied by non-invasive monitoring along with chronobiometric analysis. The BP and HR 24-h pattern was seen to preserve its circadian rhythm in both aged athletes and sedentary elderly. The analysis reveals that the aged athletes show a higher mesor for systolic BP and a lower mesor for diastolic BP and HR. The daily pressure load, as the integral of the BP 24-h values multiplied by the HR mesor, is lower in aged people practising sport as compared to age-matched individuals with sedentary habits. The spectral analysis reveals that physical exercise acts to change the time structure of BP and HR 24-h patterns. The conclusion is drawn that active sport plays beneficial effects in aged people because of a lower pressure load. PMID- 1745831 TI - [24-hour blood pressure: noninvasive monitoring and biometric analysis in relation to age]. PMID- 1745832 TI - [Isoniazid-induced vasculitis. Description of a case of pericarditis with cardiac tamponade and multisystemic involvement]. PMID- 1745833 TI - Detection of normotension, borderline and hypertension cutoffs in a population evaluated by non invasive blood pressure monitoring. AB - The 24-hour blood pressure (BP) average value in normotensive and hypertensive subjects is not defined. In 329 subjects three occasional blood pressure data were measured. The same day a non invasive 24-hour blood pressure monitoring was performed. The average of the occasional blood pressure and the average of the 24 hour blood pressure data were compared. In many cases the occasional blood pressure average was not strictly linked with the 24-hour blood pressure average. A statistical procedure (K-Means Cluster Analysis) was performed separately on occasional blood pressure values and on the hourly blood pressure average of the whole day. By this method three clusters of subjects were selected to evaluate the occasional and the 24-hour blood pressure cluster's cutoffs. The cluster's blood pressure cutoffs evaluated on occasional blood pressure values were not dissimilar from the blood pressure values suggested by literature for normotensive, borderline and hypertensive groups. The K-Means Clusters Analysis seems an interesting statistical method to research the subsets in a population evaluated by 24-hour blood pressure monitoring. We suggest that the 24-hour BP cutoffs evaluated in the three cluster groups may be considered as indicative for a clinical diagnosis of normotensive, borderline and hypertensive state. PMID- 1745834 TI - [Current aspects of the diagnosis of arterial hypertension]. AB - Arterial blood pressure (BP) is widely believed to be a main risk factor for cardiovascular diseases. The chance to develop some kind of vascular injury is almost exponentially and continuously related to BP values at a given age. In accordance, the WHO stated the upper limits for diastolic and systolic BP beyond which it is reasonable to anticipate a clear statistic advantage from the hypotensive treatment (of either pharmacologic or other kind). However many studies have shown that the relation coefficient between BP values and the occurrence of cardiovascular diseases is on the whole quite weak, even under rigorously controlled conditions. This could be, at least in part, due to the fact that the severity of the cardiovascular damage depends on the "global" hypertensive load continuously charging the patient's cardiovascular system along the whole life: the "random" measurement of the BP is indeed a poor statistical index of such load because of the wide variability of BP with time. Thus many sources of BP variability have been studied, in order to develop multiple measurement methods of BP monitoring hopefully with more prognostic power. In this article we review the major problems inherent to the methodological development of the serial full-automatic sphygmomanometric ambulatory BP monitoring, such as its concordance with different more traditional techniques, the statistic effectiveness of intermittent (versus continuous) sampling, the psychological impact of multiple cuff inflations during the day and the night.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745835 TI - [Ion transport in erythrocytes: a universal physiological model. Reflections on the pathogenesis of hypertension]. AB - The red cell represents a useful model for the study of general pathophysiological mechanisms, because of its availability and the relative easiness of the methodological approach due to the absence of nucleus and organelles. Particularly, most of the transmembrane ion transport systems, which control the homeostasis of intra- and extracellular electrolytes, have been firstly discovered in the red cell membrane. The pathophysiological importance of these transport systems is often extended to non haematological diseases like essential hypertension. Several reports from different laboratories have established that the red cell Na+/Li+ countertransport is stimulated in patients with essential hypertension. The regulation of Na+/Li+ countertransport, relationship with plasma and membrane lipids and the possibility of modulating its activity by dietary interventions, are focused in the last part of this review. PMID- 1745836 TI - [Cerebral infarction: lacunae]. AB - Lacunae are small deep cerebral infarcts which are believed to occur in hypertensive patients, producing characteristic clinical syndromes. Previous reports suggested to differentiate this type of stroke from other cerebrovascular diseases, but failed to provide any evidence that this classification is useful in clinical practice. We reviewed the present literature concerning pathogenesis, clinical features, diagnostic, and therapeutic aspects of lacunae and we established that current concepts in lacunar stroke are inadequately supported. Although lacunar syndromes are reported to be correlated with lacunar infarcts, these syndromes are also described in patients with different pathological findings. The assumption that lacunae always result from a distinct and specific small-vessel arteriopathy is not confirmed; in fact, an atheroma may occlude a single perforating artery at the base of the brain as well as larger arteries. Lipohyalinosis, initially referred to as the underlying pathologic vascular lesion specific for lacunae, is found most commonly in a subset of patients with severe hypertension associated with multilacunar dementia. Large infarcts and hemorrhages are reported to coexist with lacunae in autoptic and neuroradiological studies; intracranial atherosclerosis is associated with lacunae as well as with large superficial infarcts. The percentage of patients with hypertension is approximately the same regardless of type of the infarct, lacunar or cortical. Diagnostic criteria are not clear-cut: clinical onset, neurological examination, and assessment of risk factors are unable to take lacunae apart from other infarcts; the size of the lesion, but not the site or the pathogenesis, determines clinical course, degree of motor deficit, and prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745837 TI - [Minor donor of bone marrow graft: medico-legal aspects]. AB - Bone marrow transplantation can provide long-term disease-free survival when used as therapy for a variety of lethal disorders. Authors discuss about the underage donor consent and review the literature. In conclusion they consider that Bone Marrow donation is too important to leave its decision only to parents; they suggest to institute professional committees that consider donor will and verify on which basis he expresses his consent. PMID- 1745838 TI - Growth factors and the control of human teratoma cell proliferation. PMID- 1745839 TI - Role of heparin-binding growth factors in embryonic tumors. PMID- 1745840 TI - Cytogenetic investigation of gonadal carcinomas in situ in syndromes of abnormal sexual differentiation. PMID- 1745841 TI - Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo. AB - The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well tolerated. Both patients and investigators judged it efficacious. PMID- 1745842 TI - Effect of standing versus sitting position on spirometric indices in healthy subjects. AB - This study examined the effect of the standing versus the sitting position on spirometric indices in 94 healthy non-obese adult subjects (41 men and 53 women) with the order of testing randomised. On average all the spirometric indices examined, except the peak expiratory flow rate, were higher in the standing compared to the sitting position although the change was only significant at the 5% level for FEV1 in women. The fall in FEV1 with the change in position was statistically related to the ponderal index but not to age, height or the initial lung function level. A uniform posture for spirometry is recommended in epidemiological studies examining longitudinal trends in lung function, as well as in cross-sectional aetiological studies examining, for instance, the effects of environmental and/or occupational exposures. A uniform posture is also recommended for clinical studies which involve repeated measurements over time, for instance to measure the effect of treatment or the natural history of airways disease. PMID- 1745843 TI - Evolution of physiological variables in patients with chronic obstructive pulmonary disease before and during long-term oxygen therapy. AB - In 24 patients with severe chronic obstructive pulmonary disease (COPD), we investigated the evolution of pulmonary volumes, arterial blood gases (ABG) and mean pulmonary artery pressure (PAP), before (T0-T1) and during (T1-T2) long-term oxygen therapy (LTO). LTO was initiated at T1 on usual criteria (PaO2 persistently less than or equal to 55 mm Hg) and was given during greater than or equal to 16 h/day. The T0-T1 period ranged from 12 to 186 months (mean 53 +/- 41 months) and the T1-T2 period from 12 to 120 months (mean 44 +/- 30 months). There was a significant worsening of the obstructive pattern (FEV1 decreasing from 1,084 +/- 326 to 879 +/- 318 ml, p less than 0.005) and of ABG (PaO2 decreasing from 58.2 +/- 9.2 to 51.6 +/- 6.5 mm Hg, p less than 0.01) before the onset of LTO, whereas there was a rather good stability of ABG during LTO and the changes in pulmonary volumes were modest and statistically nonsignificant (FEV1 decreased from 879 +/- 318 to 809 +/- 247 ml). PAP tended to increase from T0 to T1 and to decrease from T1 to T2, but these changes only reached the level of statistical significance when they were expressed as changes per year (+1.0 +/- 2.7 vs. -1.3 +/- 4.5 mm Hg, p less than 0.05). The evolution of physiological variables was nearly identical in subgroups of patients who had died (n = 13) or were still alive (n = 11) at the time of data collection (T3) and this held particularly true for PAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745844 TI - Bilateral bronchoalveolar lavage in progressive systemic sclerosis: interlobar variability, lymphocyte subpopulations, and functional correlations. AB - Bilateral bronchoalveolar lavage (BAL) was carried out in right middle and left upper lobes of 22 nonsmoking females suffering from progressive systemic sclerosis in order to assess interlobar differences and functional correlation of the BAL composition. The patients' age ranged from 20 to 66 years, and the mean disease duration was 10.4 years. The most frequent finding was a mild BAL lymphocytosis (right in 11 of 22 patients; left in 8 of 22), but eosinophilic (right in 11 of 22; left in 5 of 22 patients) and neutrophilic (right in 9 of 22 patients; left in 1 of 22) alveolitis was recognized as well. Differential counts suggestive of alveolitis limited to one of the lavaged lobes were demonstrated in about one fourth of the cases. Including increased cellularity among the criteria of pathological BAL fluid composition, 14% of the subjects showed bilateral BAL results within the normal range. OKT8-positive lymphocytes were significantly increased in 3 patients, but the mean values were not. Total lung capacity, vital capacity, and forced expiratory volume in 1 s correlated inversely with BAL neutrophil (p less than 0.05) and granulocytic (p less than 0.01) differential counts; the strongest, positive correlation was demonstrated regarding the lymphocyte/granulocyte ratios (p less than 0.0005). In conclusion, several patterns of alveolitis as well as a bilaterally normal BAL composition were found in our series; moreover, even if inhomogeneous alveolitis did occur, a single lavage performed in the right middle lobe correctly detected or excluded the presence of an alveolitis in 95% of our patients. PMID- 1745845 TI - Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. AB - Although diffuse panbronchiolitis (DPB) has carried a poor prognosis, long-term low-dose administration of erythromycin (EM) is very effective. We administered EM at a daily dose of 400-600 mg to 19 DPB subjects for more than 2 months. Sixteen subjects were relieved from productive cough and dyspnea, and their chest X-ray pictures were improved. We performed a pharmacokinetic study of EM in 11 DPB subjects (8 responders; 3 nonresponders) after the long-term low-dose administration. The maximal serum and sputum levels of EM were below the MICs of clinically pathogenic H. influenzae and P. aeruginosa which were often isolated from the sputum of DPB patients. No difference was observed in the absorption of EM between responders and nonresponders. The results suggested that DPB patients might respond favorably to EM due to mechanisms other than antibacterial activity. Individual variation in the absorption of EM was observed. As EM was effective at very low serum and sputum levels, it was suggested that even 200 mg/day of EM would be effective in DPB patients who had high serum and sputum EM levels and it was necessary to monitor the concentrations of EM in serum and sputum for the treatment of DPB to determine the appropriate dose of EM individually. PMID- 1745846 TI - Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections. AB - The efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children. PMID- 1745847 TI - Accuracy and response time of a portable pulse oximeter. The Pulsox-7 with a finger probe. AB - We studied the performance of a portable pulse oximeter in 123 consecutive adult patients by spot-checking with a finger probe and by spectrophotometry of oxygen saturation on a simultaneous arterial blood sample. 88 patients were overtly hypoxemic (HbO2 less than 90%) and 26 showed severe hypoxemia (HbO2 36-70%). The differences between the two methods showed a skewed distribution with a positive tail due to the over-estimation of lower saturation values by the pulse oximeter. Overall, the 95% confidence interval for the median difference ranged from -0.6 to +0.5%. The limits of agreement (distribution-free 95% confidence interval for the sample) were -5.8 to +11.6%. Pulse oximetry can be recommended as a first assessment of the respiratory balance only if a cut-off value of HbO2 equal to 90% in nonsmoking, air-breathing subjects is acceptable. The finger probe implies a response delay of approximately 30 s, making the instrument rather insensitive to short hypoxemic transients. With a predictive value around 90%, the pulse oximeter may be a useful portable screening tool. PMID- 1745848 TI - Reproducibility of the vesicular breath sounds in normal subjects. AB - Nonfiltered (NF) lung sounds from the apical area of the heart along with lung volumes and ECG signals were recorded from 5 normal subjects. The signals were digitized and subjected to three methods of heart sound cancellation: 75-Hz high pass filtering (75 HF), ECG-triggered blanking (BL) and adaptive noise cancelling (AF) [IEEE Trans. Biomed. Engng 33: 1141-1148, 1986]. The sound signals were then subjected to the fast Fourier transform algorithm to obtain power spectra. Five breaths from each subject were analyzed, and their spectra were similar and slightly skewed to the right. The average values of mean, median and mode frequencies of the whole breath of 5 subjects, respectively, were for NF: 64.62 +/- 3.74, 44.57 +/- 2.06 and 36.75 +/- 1.79 Hz; for 75 HF: 150.42 +/- 17.49, 114.02 +/- 6.43 and 86.16 +/- 3.13 Hz; for BL: 81.76 +/- 6.02, 52.36 +/- 2.79, 41.10 +/- 3.15 Hz; for AF: 96.87 +/- 11.58, 68.23 +/- 10.44 and 52.25 +/- 8.97 Hz. These values showed no differences between subjects. The F values obtained by the two-way analysis of variance of all breaths of all subjects (mean, median, mode) were: NF: 0.161, 0.341, 0.089; 75 HF: 0.455, 0.042, 0.085; BL: 0.108, 0.082, 0.057; AF: 0.130, 0.204, 0.113 (all p greater than 0.1). The data revealed a remarkable lack of variation within and between subjects, suggesting similar sites and mechanisms of production and transmission. PMID- 1745849 TI - Effect of exercise on lung transfer factor for CO in smokers. AB - The lung transfer factor for carbon monoxide was studied in 24 apparently healthy smokers and in 24 well-matched non-smokers at rest and during exercise. Single breath and steady state (TLcoss) transfer factors for carbon monoxide, the Krogh constant, and the capillary blood volume were significantly lower in smokers. Exercise increased minute ventilation to a similar extent in both groups, but significantly lower values of TLcoss were measured in smokers than in non-smokers during mild and moderate grades of exercise (p less than 0.001). This difference in TLcoss may be attributed either to the difference in capillary blood volume or to increased inhomogeneities with regard to alveolar ventilation and perfusion due to airway damages in smokers, or to both factors. PMID- 1745850 TI - Clinical and pathological features of tuberculous pleural effusion and its long term consequences. AB - A retrospective study of 83 cases of tuberculous pleural effusion showed that the mean age of the patients was 44 years and 10 patients (12%) were over the age of 70. Pleural fluid was smear positive for tubercle bacilli in none but culture positive in 23% of the cases. Pleural biopsy was a more sensitive method of diagnosis with granulomatous inflammation seen in 97% of cases. Five patients developed significant pleural thickening during chemotherapy requiring decortication. Twenty-two patients with tuberculous effusion diagnosed and treated over 2 years previously were traced for reassessment. None of them had significant pleural thickening and lung function tests did not show significant impairment compared to matched control subjects. PMID- 1745851 TI - Thrombosis-inducing activity in plasma of patients with acute respiratory tract infection disappears after treatment. AB - Thrombosis-inducing activity (TIA) was identified in plasma from 16 of 27 patients (59%) with acute respiratory tract infections. On the other hand, it was present in only 9 of 79 subjects (11%) with chronic lung diseases and 4 of 49 healthy volunteers (8%). In the patients with acute respiratory tract infections, there were significant elevations in plasma fibrinogen, C-reactive protein and erythrocyte sedimentation rate in the TIA-positive group compared with the negative group. Plasma TIA disappeared in all of the 8 patients who were retested for TIA 2-5 weeks after they became disease free. Pneumonia was induced in rabbits by transbronchial injection of viable Escherichia coli. TIA was not present in plasma from normal rabbits, but it appeared in plasma collected 3 days after injection. It then disappeared after 1-2 weeks of treatment with antibiotics. TIA may serve as a marker for inflammatory responses and be a factor responsible for elevated blood coagulation activity in patients with acute infectious diseases. PMID- 1745852 TI - Effects of chronic acid-base changes on the rebreathing hypercapnic ventilatory response in man. AB - The CO2 rebreathing method can be very useful to test the hypercapnic ventilatory response in patients, including those with chronic acid-base changes (e.g. chronic metabolic acidosis due to renal failure). The ventilatory response to hypercapnia (CO2-R) was measured in 4 normal men by the rebreathing method under control conditions (CaCO3: 0.1 g.kg-1.day-1) and with induced metabolic acidosis (NH4Cl: 0.3 g.kg-1.day-1) and alkalosis (NaHCO3: 0.7 g.kg-1.day-1). The slope of the CO2-R did not change as a result of the acid-base alterations, but was shifted to the left of normal by metabolic acidosis, and to the right by metabolic alkalosis. These results compare favorably with previous reports on the CO2-R as measured by the steady-state technique, and validate the rebreathing method as a reliable and useful technique for evaluating CO2-R in man with altered acid-base states. PMID- 1745853 TI - Effects of nifedipine on diffusing capacity and pulmonary capillary blood volume in chronic obstructive pulmonary disease. A controlled study. AB - The acute dose-dependent effects of nifedipine on the pulmonary diffusing capacity for CO and other lung function indices were investigated in patients with chronic obstructive pulmonary disease (COPD) in a randomized double-blind, cross-over, placebo-controlled trial. Seventeen successive, clinically stable, moderate COPD patients with pulmonary hypertension and 15 control subjects were included in the study. The diffusing capacity of the lungs for carbon monoxide (DLCO) was measured with the single-breath method. Nifedipine (10 and 20 mg) and placebo were administered sublingually at room air. Nifedipine (10 and 20 mg) increased DLCO and DLCO/alveolar volume; however, a larger effect was observed with 10 mg. In addition, nifedipine increased the pulmonary capillary blood volume dose-dependently while arterial oxygenation was improved only with 10 mg nifedipine. Venous shunt was significantly increased with 20 mg nifedipine whereas spirometric parameters were unaffected. The percent DLCO change with 10 or 20 mg nifedipine was inversely correlated with baseline DLCO, but not with the severity of obstruction. Nifedipine did not have any effect in the control group, except for mild hypotension and a reflex increase in the heart rate. It is concluded that 10 mg nifedipine probably has an effect on the pulmonary circulation in moderate COPD patients with pulmonary hypertension. PMID- 1745854 TI - Inhaled and oral salbutamol: how effective in the prophylaxis of asthma? AB - Inhaled and oral salbutamol were compared in 12 asthmatic patients for prophylaxis in antigen-induced asthma. The patients were pretreated with 0.2- and 1.0-mg doses of inhaled salbutamol and with the standard oral 4- and 8-mg slow release (SR) salbutamol preparations. Bronchodilatation was monitored over the ensuing 3 h and protection against antigen challenge at the end of the period. On each study day the degree of baseline airway hyperreactivity was determined by histamine challenge. Precautions were taken during the antigen challenge to ensure a reproducible response. Blood levels of salbutamol were monitored at hourly intervals for the 3 h after treatment and during the asthmatic reaction subsequent to challenge. Both the 0.2- and 1.0-mg inhalations caused immediate bronchodilation as compared to a placebo (p less than 0.05), but only the 1.0-mg dose protected subjects against antigen challenge (p less than 0.05). In comparison to the placebo, no bronchodilatation was achieved with the standard 4 mg oral preparation in spite of measurable blood levels, nor were the patients protected against antigen challenge at 3 h after pretreatment. However, the 8-mg SR salbutamol caused significant bronchodilatation within 2 h and suppressed antigen challenge responses as compared to placebo (p less than 0.05). It can be concluded that doses of inhaled salbutamol higher than the conventional 0.2- or the standard 4-mg oral preparations are required to protect asthmatics against inadvertent antigen exposure. In patients who are unable to use inhalers effectively, the SR preparation can be considered as an alternative. PMID- 1745855 TI - Impaired pulmonary function in schoolchildren exposed to passive smoking. Detection by questionnaire and urinary cotinine levels. AB - Pulmonary function was evaluated by FEV1, FVC, PEF, MEF50%FVC, MEF25%FVC and MMEF in relation with passive smoking exposure in 143 children aged 6-11 years (mean age = 8.5 +/- 1.6). Passive smoking exposure was evaluated by a questionnaire and by measurement of urinary cotinine levels. Children were divided into different groups: no exposure, low exposure and high exposure. The mean values of each pulmonary function test were compared between the groups and between the different evaluations by Student's test. The evaluation of passive smoking exposure by questionnaire and by urinary cotinine levels separated homogeneous groups of children. The urinary cotinine levels were significantly lower in the non-exposed children than in the other groups (p less than 0.001). Pulmonary function tests, especially MEF50%FVC, MEF25%FVC and MMEF were significantly reduced in exposed subjects (p less than 0.05). These alterations are an index of early involvement of the small airways also in passive smokers. The greater the exposure to passive smoking, the lower the values of the pulmonary function tests. PMID- 1745856 TI - Metastatic laryngeal carcinoma mimicking pleural mesothelioma. AB - We describe an unusual case of metastatic poorly differentiated laryngeal carcinoma to the pleura resembling pleural mesothelioma in a patient with a positive history of exposure to asbestos. This case not only describes an unusual presentation of metastatic laryngeal carcinoma, but also highlights the need for special pathological techniques to distinguish nonmesothelial tumors from primary pleural mesotheliomas. PMID- 1745857 TI - Tracheobronchomegaly associated with interstitial pulmonary fibrosis. AB - Tracheobronchomegaly (TBM) is the syndrome of enlarged trachea and main bronchi associated with recurrent and chronic respiratory tract infections. A 42-year-old man with TBM and diffuse interstitial pulmonary fibrosis is described. The possible relationship between the two entities is discussed and the etiology, pathogenesis, clinical manifestations, prognosis and treatment of TBM are reviewed. PMID- 1745858 TI - Pneumoperitoneum in a patient with lymphangiomyomatosis. AB - A 32-year-old Japanese housewife with a 2-year history of retroperitoneal and pulmonary lymphangiomyomatosis had a sudden onset of severe abdominal pain. Chest X-ray and plain abdominal films showed free air under the diaphragm and a small pneumothorax in the left lower pleural space. Emergency laparotomy revealed no perforated viscera, but there was a rupture in the mid-portion of the left diaphragm. It appears that increasing pressure in the left pneumothorax burst the left diaphragm leading to pneumoperitoneum. PMID- 1745859 TI - Lymphangioleiomyomatosis: the effectiveness of radiotherapy-induced ovarian function annulment. A case report. AB - Lymphangioleiomyomatosis is an unusual disease characterized by atypical smooth muscle hyperplasia especially of the lymphatic system and affecting females in their child-bearing years. We present a case in which ovarian function was annuled through radiotherapy, instead of resorting to the most commonly used oophorectomy, since the patient's severe respiratory dysfunction made surgery inadvisable. The clinical, radiological and functional characteristics of this entity are discussed, and the therapeutic possibilities are reviewed. PMID- 1745860 TI - Subpleural silicotic nodule radiographically resembling to small bronchial carcinoma. AB - A 65-year-old woman had a solitary nodule radiologically appearing as a coin lesion with pleural indentation, suggesting primary lung cancer. Operative findings and histological examination revealed it to be a silicotic nodule. Despite the rarity of this condition, silicotic nodules should be considered among the causes of solitary or small numbers of peripheral pulmonary nodules in adults. PMID- 1745861 TI - Severe anaerobic necrotizing pneumonia complicated by pyopneumothorax and anaerobic monoarthritis due to Peptostreptococcus magnus. AB - A rare case of a severe anaerobic necrotizing pneumonia complicated by pyopneumothorax and monoarthritis due to anaerobic Peptostreptococcus magnus is described in a 20-year-old soldier. The patient's immunological status was normal. There were no predisposing underlying factors, and he was treated successfully without any residual damage. To our knowledge, a similar case has never been reported in the literature. PMID- 1745862 TI - Adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. A case report. AB - Multiple primary lung cancers, either synchronous or metachronous, are unusual. We treated a 70-year-old man with double synchronous lung cancers in the right upper lobe, an adenocarcinoma and a squamous cell carcinoma. As multiple malignant lesions in an early stage may be curable, those patients in whom a lung cancer has already been detected, and who have an increased risk, such as long history of heavy smoking or of exposure to some carcinogens, an aggressive check up should be performed and should be closely watched. PMID- 1745863 TI - Endobronchial actinomycosis associated with a foreign body. AB - We describe our findings in a 58-year-old mentally retarded patient with endobronchial actinomycosis surrounding an aspirated chicken bone foreign body. To our knowledge, this is the first report of such an occurrence. PMID- 1745864 TI - Removal of a large endobronchial foreign body with a fiberoptic bronchoscope. PMID- 1745865 TI - [Predisposition and sudden death of children]. PMID- 1745866 TI - [Rapid freezing of a beating heart]. PMID- 1745867 TI - [Exercise induced precordial T wave normalization associated with U wave inversion in detection of left anterior descending artery stenosis]. AB - Although normalization of inverted T wave is not an uncommon finding during exercise tests, it's clinical significance is still unclear. Exercise 12-lead electrocardiograms (ECGs) were recorded by using Master's 2-step or ergometer. T wave normalization in the anterior chest leads was found in 20 patients with, and 14 patients without coronary artery disease (CAD). Coronary angiography and/or exercise Tl-201 myocardial imaging were also performed in every patient. Exercise induced T wave normalization was defined as "inverted T wave at rest becoming upright during exercise". ST segment, T and U wave amplitudes were measured before and immediately after exercise. 1) All of the 20 patients (100%) with CAD demonstrated critical stenosis of the left anterior descending artery (LAD). 2) ST deviation was noted in none of the 14 patients (0%) without CAD, and in only 4 of the 20 patients (20%) with CAD. 3) T wave amplitude increased equally in patients both with and without CAD. 4) Exercise-induced U wave inversion was found in 16 of the 20 patients (80%) with CAD, whereas it was found in only 1 of the 14 patients (7%) without CAD. 5) The sensitivity of "U wave inversion" in detection of LAD stenosis was 80%, and the specificity was 93%. We conclude that exercise-induced T wave normalization associated with U wave inversion in anterior chest leads is highly indicative of the specific presence of critical LAD stenosis. PMID- 1745868 TI - [Changes in cardiac output during exercise in patients with hypertrophic cardiomyopathy: the study of these influences on exercise intolerance]. AB - In order to investigate the relation between exercise intolerance and cardiac output (CO) increase during exercise in patients with hypertrophic cardiomyopathy (HCM), submaximal treadmill exercise (Sheffield protocol) with simultaneous measurement of CO and oxygen uptake (VO2) by acetylene rebreathing method were performed in twelve patients with HCM who had no demonstrable left ventricular outflow obstruction and fifteen control men. The measurements were made at rest, during exercise and recovery. 1) At rest cardiac index (CI) in patients with HCM was significantly less than in control subjects but the difference was small (HCM: 1.9 +/- 0.35 l/min/m2 vs control: 2.2 +/- 0.38, p less than 0.05), and was almost the same during light exercise (stage 1-3), but clearly increased during middle to submaximal stages (stage 4 and 5) (stage 5: 4.5 +/- 1.25 vs 8.0 +/- 1.30, p less than 0.01). 2) Heart rate was not different in both groups at rest, during exercise and recovery, which was considered to explain that the difference of CI was derived from that of stroke index (SI). 3) The change of VO2 showed the same tendency as that of CI. The difference increased considerably during the middle to submaximal stages (Stage 5: 15.3 +/- 1.42 ml/min/kg vs 25.4 +/- 4.42, p less than 0.01). 4) During recovery, CI and VO2 in patients with HCM indicated a delay of beginning to decrease toward the rest level, compared with control subjects. 5) VO2 was closely related to CI (r = 0.90, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745869 TI - [A case of lupus erythematosus preceded by right heart failure due to pulmonary hypertension]. AB - A 40-year-old woman was admitted because of increasing exertional dyspnea. Right heart failure was suggested by the presence of hepatomegaly, pretibial edema and also echocardiographic findings. Physical examination and echocardiography showed no evidence of valvular disease or congenital heart disease except for right ventricular dilatation and tricuspid regurgitation. The ventricular septum deviated toward the left ventricle throughout the cardiac cycle, but left ventricular function was preserved. Severe pulmonary hypertension averaging 44 mmHg was revealed by cardiac catheterization. Digital subtraction angiography and pulmonary blood flow scintigraphy showed no evidence of pulmonary artery embolism, and no interstitial pulmonary lesions that might have caused pulmonary hypertension were recognized. Hypergammaglobulinemia suggested an autoimmune disorder, and signs of systemic lupus erythematosus (SLE), such as pleural effusion, proteinuria, lymphocytopenia, LE cell phenomenon and antinuclear antibodies were present. Several autoimmune diseases are known to be causative factors of pulmonary hypertension. However, only ten cases of SLE complicated by pulmonary hypertension have been reported the present one. These cases were characterized by a high incidence of Raynaud's phenomenon and positivity for anti RNP antibody. In our present case, SLE activity was suppressed using prednisolone, but pulmonary hypertension persisted and the patient eventually died due to right cardiac failure. Judging from the clinical course of the ten reported cases of SLE-pulmonary hypertension, there seems to be no hope of improving the pulmonary hypertension once it has become established. Therefore it is important to detect and cure pulmonary hypertension as early as possible. PMID- 1745870 TI - [A case of anomalous origin of circumflex artery from right sinus of valsalva recognized by transesophageal echocardiography]. AB - A 56-year-old man visited our hospital for further examination of resting electrocardiographic abnormality. Positive exercise stress resulted in mild chest discomfort and 1.5 mm ST depression in II.III.aVF leads. Myocardial imaging perfusion with thallium-201 was normal and an anomalous origin of the left circumflex coronary artery from the right aortic sinus was observed by coronary angiography. MRI showed that the vessel running behind the aorta was connected to the right Valsalva's sinus. Furthermore, transesophageal echocardiography revealed that the vessel connected to the lateral wall of the left ventricle was running from the right Valsalva's sinus between the aorta and left atrium. The above results indicated that this vessel was the left circumflex artery. Although myocardial infarction or sudden death in patients with coronary anomaly has been discussed, the mechanism is still unknown. The present case is a rare one in which the anatomical relation between the anomalous coronary and the great vessels was directly detectable by transesophageal echocardiography. Transesophageal echocardiography is useful for the assessment of this type of coronary anomaly. PMID- 1745871 TI - [A case of ventricular septal defect associated with active infective endocarditis which was successfully treated by triple valve replacement and ventricular septal defect patch closure]. AB - A 47-year-old man was hospitalized in May, 1990, because of breathlessness and continuous fever which appeared about 4 weeks after he had had his periodontic tooth removed in December, 1989. He had been diagnosed as having ventricular septal defect (VSD) at the age of 6 years. When he was hospitalized, he was in a condition of class IV by NYHA classification, with a white blood cell count of 17,300/mm3, an increase in CRP, a red blood cell sedimentation rate of 108 mm/hr, and positive alpha-streptococcus in blood culture. His cardiothoracic ratio was 64% with signs of pulmonary congestion on a chest X-ray film. Echocardiography revealed the presence of VSD and huge vegetations on the tricuspid, mitral and aortic valves. He was considered to have active infective endocarditis (AIE) which had presumably been provoked by VSD and the tooth removal. Penicillin G at a daily dose of 20 million units and gentamicin at a daily dose of 80 mg were intravenously administered to treat the alpha-streptococcus infection for about 4 weeks. Furosemide was used for congestive heart failure. Since, although his cardiac function appeared to have been improved, the signs and symptoms of the infection persisted, triple valve replacement for the tricuspid, mitral and aortic valves and patch closure of the VSD were performed 4 weeks after the hospitalization. The operation revealed inflammatory lesions extending from the endocardium of the right ventricle to the mitral valves through the VSD, and huge vegetations on the tricuspid, mitral and aortic valves. The operation was successful and the inflammatory areas gradually disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745872 TI - [A case of complete absence of the left pericardium coexisting with straight back syndrome]. AB - A case of complete absence of the left pericardium coexisting with straight back syndrome in a 30-year-old female is presented. She had been asymptomatic, but was referred to our hospital because of an abnormal finding on a chest X-ray obtained during a routine physical examination. The posteroanterior view of the chest X ray showed displacement of the right and left cardiac border to the left and bulging of the left cardiac border. The lateral view showed loss of normal thoracic curvature and also demonstrated the straight back syndrome. Echocardiography showed paradoxical movement of the ventricle septum, hyperkinetic movement of the free wall of the left ventricle and enlargement of the right ventricle. Computed tomography and magnetic resonance imaging with an artificial pneumomediastinum clearly showed rotation of the heart into the left hemithorax, prominence of the pulmonary trunk and pneumopericardium. Hence the diagnosis of the complete absence of the left pericardium coexisting with straight back syndrome was made. Congenital defect or absence of the pericardium are rarely reported. Only about 120 cases have been described in Japan. Only a few cases have been diagnosed antemortem. Most of them were found by chance during operations or on installation of an artificial pneumothorax. We suggest that an artificial pneumomediastinum as well as a pneumothorax is useful for the diagnosis of the absence of the pericardium. This is the first reported case of a complete absence of the left pericardium coexisting with straight back syndrome. PMID- 1745873 TI - [Pulmonary vascular changes in the collagen vascular diseases]. PMID- 1745874 TI - [Effect of acid rain on respiratory system]. PMID- 1745876 TI - [Laser angioplasty]. PMID- 1745875 TI - [Respiration and circulation under weightlessness]. PMID- 1745877 TI - [pH correction]. PMID- 1745878 TI - Role of the renal nerves in hypertension. PMID- 1745879 TI - Insulin resistance and hyperinsulinemia: implications for the pathogenesis and treatment of hypertension. PMID- 1745880 TI - The kidney in the pathogenesis of hypertension. PMID- 1745881 TI - Antihypertensive therapy and the progression of chronic renal disease. Are there renoprotective drugs? AB - The pathogenesis of hypertensive glomerular injury is complex, involving both hemodynamic and nonhemodynamic factors. One can therefore confidently predict that a wide variety of disparate therapeutic interventions, pharmacologic and nonpharmacologic, may be effective in arresting or slowing progressive glomerular injury. Based on the experimental and clinical literature available to date, it is clear that glomerular capillary hypertension is an important pathogenetic factor in this disease and that lowering of Pgc with antihypertensive drugs is associated with prevention of glomerular injury. Furthermore, the CEI may have a special renoprotective effect compared to other antihypertensive agents, most likely due to their unique renal hemodynamic actions. Pending the results of well designed clinical trials, converting enzyme inhibitors represent the antihypertensive agents most likely to arrest the progressive decline in renal function observed in patients with hypertension and chronic renal failure. The calcium channel blockers are effective antihypertensive agents in patients with chronic renal failure, but whether they confer specific renoprotective effects remains uncertain. Since a large number of patients with chronic renal failure require more than one antihypertensive drug for adequate blood pressure control it may be of interest to evaluate the benefits of drug combinations. In this regard, it is possible that a combination of a CEI and a CCB may have complimentary effects in protecting the kidney. The development of these new classes of antihypertensive agents has had a major impact on the treatment of patients with chronic progressive renal failure. Future studies will hopefully clarify the optimal antihypertensive therapeutic regimen and allow us to move closer to the goal of eliminating end-stage renal failure. PMID- 1745882 TI - Renal consequences of salt and hypertension. PMID- 1745883 TI - Hypertension and diabetes. PMID- 1745884 TI - Resistant hypertension. PMID- 1745885 TI - Hypertension in pregnancy. PMID- 1745886 TI - [What is your diagnosis? Ewing sarcoma of the radius with lung metastases]. PMID- 1745887 TI - [Type 1 or Type 2 diabetes: diagnostic aids in clinically uncertain cases]. PMID- 1745888 TI - [Neurosurgery in old age. I: Significance of the problem--herniated disk, spinal canal stenosis--craniocerebral injuries--chronic subdural hematoma--resorptive hydrocephalus]. AB - The relative percentage of patients over 60 years who underwent operations in our clinic has greatly increased from 18% in 1874 to 27% in 1989. Postoperatively, difficulties may also result from additional medical problems, which may be cardiovascular, pulmonary, metabolic (especially diabetes mellitus), increased thromboembolism in origin as well as from the reduced tendency to neurological recovery in elderly patients. On the other hand, advances in diagnostics and surgical treatment often make it possible to help even these patients effectively today. The clinical pictures which are especially frequent in our hospital are specified below. Disc herniations: Soft nucleus-pulposus herniations occur in every age group. In elderly patients, the osseous constriction of the lumbar canal (especially by spondylarthrosis) often leads to spinal claudication. Functional myelography with myelograms taken in the sitting and the standing position is important for preoperative appraisal. On the basis of the clinical/neuroradiological findings, it may be decided whether a selective or an extended decompression is necessary. Larger-scale decompressions are mostly possible in this age group without postoperative instability, with good results in more than 80% of the cases. In our clinic, anterior microsurgical decompression without graft is the most frequently used procedure in cervical disc herniations/spondylosis, a method which is well tolerated by spinal cord and nerve roots: 75% simple anterior discectomies/spondylectomies compared to only 25% classical Cloward operations with bone grafts. We use intervertebral bone grafts only in severe spondylosis and/or instabilities, if necessary in combination with metal plates (e.g. in the context of cervical myelopathy). Craniocerebral injuries: Epidural hematomas and CSF fistulae, but also circumscribed space-occupying contusions have a relatively favorable prognosis in every age group. The older the patient, the more serious is the acute subdural hematoma, which is often associated with extensive contusions, although surprisingly good recoveries are occasionally possible postoperatively even here. Detailed scrutiny of all prognostically relevant factors is important. In borderline situations we give the patient a chance in order to take later action, depending on the course. Chronic subdural hematomas are especially frequent and readily dealt with surgically in patients over 60 years. The simple borehole drainage to the outside is often sufficient. In extensive excreting membranes, which are especially frequent in elderly patients, we prefer today a subdural peritoneal drainage for six to eight weeks to the very much more burdensome craniotomy: The relatively simple operation allows an early mobilization and almost always a prompt healing. Hydrocephalus male resorptivus is also very much more frequent in this age group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1745889 TI - [Orthotopic liver transplantation--indications and results]. AB - Indications for and results of orthotopic liver transplantation (OLT) were modified over the past ten years by new immunosuppressive agents, earlier timing of transplantation and better knowledge of potential complications. In 1990, OLT appears justified in the treatment of all liver disease threatening life, in the absence of contraindications and other possible treatments. Between July 1987 and December 1990, 21 patients were transplanted at the Geneva University Hospital. Three children received part of an adult liver (two or three segments), using the reduced-size liver transplantation technique. Four OLTs had to be performed in an emergency situation. Two patients died within six months of transplantation, one after 7.5 months, and the last patient died after one year from cancer recurrence. 17 patients are presently alive (81%) at 4 to 39 months (median 14 months) following OLT. More than the mere survival, however, the quality of life regained after transplantation prompts us to consider transplantation early in the progress of the disease. PMID- 1745890 TI - [A case from practice (232). Stage I sarcoidosis with erythema nodosum and febrile arthropathy (Lofgren syndrome)]. PMID- 1745891 TI - [Principles of gene technology and potentials of DNA diagnosis]. AB - Gene technology offers new potentialities for medicine in the diagnosis, treatment and also prevention of disease. DNA diagnostic procedures are already a cornerstone of genetic counselling. The number of mutated genes identified and, as a consequence, the number of disorders diagnosable with a molecular genetic approach, is steadily increasing. Since a given gene is present in practically all somatic cells, it can, irrespective of its expression, be analyzed using white blood cells or chorionic vili as a source of DNA. This results in an extension of disorders diagnosable before birth (prenatal diagnosis) or before its clinical manifestation (presymptomatic diagnosis) as well as in the reliable recognition of clinically healthy carriers of defective genes. DNA diagnostic procedures have already gained practical application in oncology, immunology or forensic medicine. The methodology of molecular biology allows the analysis of infectious agents in tissues or body fluids that are only present in a latent state. We are only at the dawn of the century of molecular medicine. However, our knowledge of the cause and the nature not only of rare single genetic diseases but also of common multifactorial disorders, such as cardiovascular diseases, cancer or autoimmune diseases, is increasing through gene technology. Therefore, on the one hand the new genetics holds out numerous promises and hopes, while on the other hand, a future characterized by exorbitant genetic testing increases an irrational fear of this technology in the public. Members of the medical profession must interest themselves in molecular genetics in order to be able to follow the development of modern medicine but also to inform their patients and the general public about the new possibilities and limitations, as well as any risks, of genetic testing. This is the only way to ensure proper use of gene technology in medicine without irrational legal restrictions imposed by an ill informed public. PMID- 1745892 TI - [Diagnosis and treatment of pulmonary infection due to Mycobacterium malmoense]. AB - To date more than 150 patients with Mycobacterium malmoense disease have been reported. These infections are rare and only in one case, so far not published, is this species associated with Aids. Most reported cases were seen in northern Europe. We present three pulmonary cases from Switzerland. M. malmoense causes lung disease resembling tuberculosis clinically and in chest X-ray. Disease is considered to be present when two and more sputums or bronchial washings are acid fast bacilli smear-positive and culture-positive. M. malmoense grows slowly on egg-based bacteriological media; the incubation time is at least 6 weeks and the use of special solid or liquid media is recommended. Person-to-person transmission is rare and, in contrast to tuberculosis, isolation of the patient is not necessary and subsequent close contact persons do not need to be evaluated. It seems that a combination of isoniazid, rifampicin and ethambutol given for more than 12 months is the best regimen. PMID- 1745893 TI - [The need of providing a comprehensive civil service for the management of geriatric health care problems in the coming decades]. AB - From (1) the Swiss population census 1980, (2) the calculations of the Swiss Federal Office of Statistics, referring to the probable age composition of the stable Swiss population from 1990 to 2025 (scenario 2A-86), (3) the meta-analysis of Jorm et al. [8] on the prevalence of dementia, and (4) a study of the Swiss Federal Office of Statistics on the nursing personnel employed by inpatient institutions for the care of the aged, it is concluded that the number of elderly patients suffering from moderate to severe dementia will increase in Switzerland from 48,000 to 92,000 during the years 1980-2020. In 1990 the nursing staff for the ambulatory and inpatient care of 62,900 patients with dementia numbered 17,100 full-time positions. The calculated need for such positions was 37,700 in 1990 and will be 55,200 in 2020. This major shortfall in nursing capacities, now and in the near future, can probably not be covered by an extension of extrahospital services and certainly not by increased training of nursing personnel. By analogy with the obligatory military service for young men in Switzerland, an obligatory civilian service for men and women, for the care of the aged, is therefore proposed. PMID- 1745894 TI - Common horse sense. PMID- 1745895 TI - The danger from Kuwait's air pollution. PMID- 1745897 TI - Sharper image. Picosecond photography may reveal tumors. PMID- 1745896 TI - Crossed lines. Eve's family tree may have a few branches from Adam. PMID- 1745898 TI - Digital dyslexia. Neural network mimics the effects of stroke. PMID- 1745899 TI - Profile: Gertrude Belle Elion. The satisfaction of delayed gratification. PMID- 1745900 TI - Iron deficiency. PMID- 1745901 TI - The Assessment Unit of the Epilepsy Centre, Quarriers Homes. AB - The work of the Assessment Unit in the Epilepsy Centre, Quarriers Homes, Scotland is described. One hundred and thirty patients with severe epilepsy were admitted over a three year period for investigation of seizures and rationalisation of therapy. The degree of psychomotor impairment due to epilepsy itself, or to anti epileptic drugs was estimated. Cognitive functioning and levels of ability with interpersonal relationships were measured and plans were drawn up for rehabilitation. A plea is made for NHS funding to support the provision of this service for people with epilepsy. PMID- 1745902 TI - Decisions to limit treatment in a neurosurgical unit: an aspect of audit of mortality. AB - The monthly audit of deaths in this regional neurosurgical unit notes decisions to limit treatment recorded in the case-sheet. In 1988 a treatment-limiting decision was noted in 67 of 131 deaths (51%). In 40% of these the decision was made soon after admission; in these patients the mean time to death was 1.5 days (median one day). When the decision was made later, the mean time for admission to death was 6.8 days (median five days). Regular audit provides an opportunity to discuss the appropriateness of such decisions in various circumstances. PMID- 1745903 TI - Unplanned re-attendance in the accident and emergency department. AB - The notes of patients who re-attended the Accident and Emergency Department with a problem for which they had already been seen and treated were reviewed over a five-week period. Such patients comprised 2.5% of total attendances. The commonest reason for re-attendance was persistent pain following an injury and of such patients, about a half required a significant change in management. It was estimated that two-thirds of re-attendances were unavoidable. Twenty patients were admitted following re-attendance, and of these, two had serious medical conditions which were missed on initial presentation. The role of senior Accident and Emergency doctors is discussed in the light of these findings. PMID- 1745904 TI - What do Scots die of when abroad? AB - Information was obtained on 952 persons who travelled from Scotland between 1973 and 1988 and who died while abroad. In the older age group cardio-vascular disease was the major cause of death whereas in the younger group traumatic deaths were commonest. Most died in the holiday resorts bordering the Mediterranean and the question is posed on the need for specific advice to those who are most vulnerable before embarking on overseas travel. PMID- 1745905 TI - Two coronary artery fistulae in a patient with temporal arteritis and chest pain. AB - A 59-year-old woman with a history of cardiac sounding chest pain was investigated by coronary arteriography. Two unsuspected fistulae were found. The fistulae originated from the distal right coronary artery and the diagonal branch of the left coronary artery. Both drained into the left ventricle. She was also found to have temporal arteritis, treatment of which abolished the chest pain. PMID- 1745906 TI - Politics, society and medicine in the 18th century. AB - Medical theory and practice in the 18th century reflected the thought and culture that the Renaissance had fashioned. This article draws attention to the political and social changes of the period and notes their inter-relationship with the changes that occurred in medicine. PMID- 1745907 TI - Chronic chest pain in a 16-year-old girl from the Middle East. PMID- 1745908 TI - Hand injuries in adults. AB - The radiologist plays an important role in the evaluation of hand injuries. Although the detection of fractures is important, recognition and delineation of soft tissue damage is equally vital. If only soft tissue injuries exist, plain film findings are often nonspecific. Nevertheless, they can give helpful clues in evaluating ligaments and tendons. It is especially important for the radiologist to be knowledgeable of these soft tissue injuries because, in an emergency room setting, the radiologist may be the physician most familiar with the spectrum of injuries and possible complications. PMID- 1745909 TI - Radiographic evaluation of wrist trauma. PMID- 1745910 TI - Trauma to the elbow and forearm. AB - Elbow and forearm trauma constitute a significant percentage of upper extremity injuries. A thorough understanding of the anatomy and mechanism of injury is necessary for obtaining the most accurate radiographic interpretation in both the pediatric and adult populations. Proper radiographic positioning and choice of the best imaging modality are crucial to ensure the best orthopedic treatment and reduce the incidence of post-treatment complications. PMID- 1745911 TI - Trauma to the shoulder girdle. PMID- 1745912 TI - Anthropology rediscovers sex. Introduction. PMID- 1745913 TI - Sex, culture and the anthropologist. AB - The apocalyptic threat of AIDS, combined with recent ethnological developments, is promoting an anthropological "rediscovery of sex." If this rediscovery is to have important and lasting effects on the development of theory, a stock-taking is in order--one which examines anthropology's historical, methodological, and practical relationship to the study of sexual behavior. Parallel theoretical directions taken in both American and British anthropology, starting in the late 1920's, resulted in a disciplinary departure from the study of sexuality, as such; sexual behavior became shielded from analytic view by a more abstract, propositional approach to society and culture. In addition to reviewing these historical trends, the paper considers elements of personal privacy and intrasocietal variation in the anthropology of sex and, with illustrations taken from the Ilahita Arapesh of northeastern Papua New Guinea, proposes that the locus of sexual behavior and experience lies in the interaction of cultural ideas and psychobiological impulses. PMID- 1745914 TI - Anthropology rediscovers sexuality: a theoretical comment. AB - Despite its reputation for openness to research on sexuality, anthropology as a discipline has only reluctantly supported such work. Anthropological research and theory developed slowly, sharing a stable theoretical paradigm (the cultural influence model) from the 1920s to the 1990s. Moving beyond determinist and essentialist frameworks still common in biomedicine, anthropological work nevertheless viewed important aspects of sexuality as universal and transcultural. Social construction theory has offered a challenge to traditional anthropological models and has been responsible for a recent burst of innovative work in sexuality, both in anthropology and in other disciplines, since 1975. The theoretical roots and implications of constructionist theory are explored. The intensifying competition between cultural influence and constructionist paradigms has been altered by the appearance of AIDS and the subsequent increased support for research on sexuality. On the one hand, the expansion in funding threatens to strengthen essentialist models in biomedical contexts and cultural influence models in anthropology. On the other hand, the complexities and ambiguities inherent in the sexuality under study may both reveal the strengths of constructionist approaches and spur the development of research and theory in anthropology. PMID- 1745915 TI - Sex and respectability in an age of fertility decline: a Sicilian case study. AB - The paper examines two aspects of coitus interruptus as a sexual practice: (1) how, in the age of fertility decline in Western Europe, its meaning was reinterpreted from an earlier theological view that condemned it as licentious to a nineteenth century view that emphasized restraint, and (2) how it was actually experienced by a socially stratified birth-controlling population in rural Sicily, ca 1900-1970. The sequential experiences of gentry, artisans, and peasants in the Sicilian case study of transition from high to low fertility are consistent with late twentieth-century interpretations of coitus interruptus by Foucault and others as sexually restraining yet empowering. In each group, adoption of the practice enhanced access to respectability in a context of cultural and economic change. Moreover, those who adopted the practice increasingly stigmatized married couples with high birth parities as overly dominated by their sexual instincts and unworthy of respect. PMID- 1745916 TI - Social psychology of the immune system: a conceptual framework and review of the literature. AB - The literature on psychosocial factors affecting the immune system is reviewed. The literature is summarized in terms of a provisional model accounting for immunosuppression in terms of four mutually influential explanatory constructs (dysphoric responses; immunosuppressive behaviors; adverse life experiences; and vulnerability) and the relationships among the diverse manifestations of the constructs. The literature and the summary provisional model point to directions for future research that should establish the intervening role of immunosuppression in the relationships between psychosocial factors and the disease process. PMID- 1745917 TI - The European Health and Behaviour Survey: rationale, methods and initial results from the United Kingdom. AB - The aim of this study was to assess a wide range of health-related behaviours, beliefs concerning the importance of behaviours for health, and health knowledge, using a standardized protocol suitable for translation and administration in different countries of Europe. An inventory was developed from previous literature for the assessment of substance use, positive health practices, diet and eating habits, driving behaviour and preventive health care, beliefs concerning the importance of 25 activities for health, and knowledge about the influence of seven factors (including smoking, alcohol and diet) on major diseases. The first phase of the study involved administration of the inventory to approximately 200 male and 200 female university students aged 18-30 in 20 European countries. This report concerns data collected from 419 students in the U.K., together with analyses of short-term response stability. The inventory showed adequate short-term stability. Sex differences were observed in a number of behaviours, including consumption of fats and cholesterol, salt and fibre, dieting, exercise, sun-protection, driving speed, regular dental check-ups, frequency of brushing teeth, access to doctor and blood pressure measurement. Beliefs about the importance of behaviours for health were closely associated with the occurrence or frequency of the behaviours both within and between health behaviour categories. Little relationship was observed between health behaviour and awareness of the role of these same factors in disease. Important gaps in health knowledge were identified. Data concerning the frequency of health-related behaviours is crucial to the planning of health education and primary prevention programmes. The close association between beliefs and behaviour emphasises the importance of cognitive factors, while health knowledge appears to play a less direct role. PMID- 1745918 TI - Relationship between water quality and human health: a case study of the Linggi River Basin in Malaysia. AB - Due to the increasingly documented prevalence of diarrhoeal diseases in Malaysia, a number of water-related programmes have been implemented in an attempt to improve health status through the reduction of incidence of waterborne communicable diseases associated with poor public water supplies. The implicit assumption underlying these projects is that the enhancement of the physical infrastructure, and subsequent improvements in the quality of the water supply, will substantially reduce water-related disease. The present study questions this hypothesis and uses a socio-ecological model as a framework to assess risk factors associated with the increased probability of waterborne disease. Research is centred on Port Dickson, a district which typifies existing water and sanitation conditions in much of semi-rural Malaysia. Health services utilization data and a 268-household diarrhoeal morbidity survey were used to measure the burden of illness of waterborne disease within the district and to identify predictors of morbidity. It was concluded that although treatment facilities will reduce the health burden in the region, a number of behavioural and sanitation factors may be more important and could act to minimize the potential impacts of improved water quality. PMID- 1745919 TI - Finding meaning after the fall: injury narratives from elderly hip fracture patients. AB - Hip fractures occur frequently among the elderly, often with severe medical, psychological and social repercussions. This research takes a new look at hip fracture rehabilitation, focusing on meanings and post-fracture prognostic indicators. An innovative methodological approach to narrative analysis is employed which combines ethnographic and epidemiologic techniques. Analyses of injury narratives from 80 elderly subjects interviewed soon after initial hospitalization are presented, focusing on three categories of meaning: explanatory models, sense of disability, and futurity. Insights from these narratives, as well as from questionnaires and observations, shed light on the experience of hip fracture for the elderly. In addition, aspects of the initial narratives are considered in relation to ambulation outcomes at 3 and 6 months. Those individuals who perceive their problem in a more external or mechanical fashion (caused by the environment) show greater improvement in ambulation at 3 and 6 months relative to those who show no evidence of this thinking or who perceive it as an internal or organic problem (in terms of disease or illness). Greater improvement in ambulation at 3 and 6 months is also noted for subjects whose perception of disability was consistent with more autonomy, independence, and a sense of connection with the world around them. The present study demonstrates the potential utility of narrative analysis as a data reduction approach. It also suggests the possibility of new psychosocial prognostic factors for hip fracture rehabilitation. PMID- 1745920 TI - Jidda: the traditional midwife of Yemen? AB - Contrary to what is assumed, traditional birth attendants (TBAs) do not appear to be a clearly defined category of women with specialized knowledge and experience of assistance at deliveries in the local cultural situation at village level in the Anis region of the central highlands in Yemen. In the actual design of training for TBAs in Yemen, this results in problematic provision of basic mother and child health care, in particular safe and clean deliveries to all women at village level. PMID- 1745921 TI - Do prostitutes need more health education regarding sexually transmitted diseases and the HIV infection? Experience in a Belgian city. AB - From December 1988 till April 1989 154 women who worked in clubs (120) and behind windows (34) in and around Ghent, Belgium, were interviewed about knowledge, attitudes and practices regarding Sexually Transmitted Diseases (STD) and Human Immunodeficiency Virus (HIV) infection in their professional life. Television scored best (98%) as a source of information for AIDS. A leaflet posted in every door in 1987 was mentioned in 60%. Less than half the women gave more than 7 correct answers on 11 questions about safety of sex techniques. Intercourse with condom, the sexual act mostly done, was considered safer than deep kissing, masturbation and even massage. In 10 to 20% of the professional sex contacts no condoms were used, which leads to 1000 to 4000 unprotected contacts every week in the sex industry in Ghent (population 500,000). Condom use with the private partner is exceptional. Proposals for condom use almost invariably come from the women themselves instead of from their clients. We conclude that up till now health education efforts to prostitutes and their clients were not sufficient and that they should be intensified. PMID- 1745922 TI - The Amelia Stern syndrome: a diagnosis of a condition among female physicians? AB - Numerous studies have provided numerical portraits of some of the difficulties of women physicians at work in a field that traditionally has been the preserve of men. These studies, like much of recent feminist literature, often focus on the tension between maintaining a career and being a wife and mother. They usually provide aggregate data but fail to convey compellingly the nuances and emotions involved in the issues they address. Perri Klass's recent novel, Other Women's Children, the center point of this article, provides a case study of the thoughts and feelings attached to the issues addressed by the scientific inquiries. The book deals with the experiences of a woman pediatrician in a Boston hospital, a woman who uncertainly juggles her career and family responsibilities. PMID- 1745923 TI - The Camberwell Community Survey: a summary of results. AB - The Camberwell Community Survey was carried out during 1978 and 1979 on a random sample of the population of Camberwell in south London. This is an inner city area with high deprivation indices. 800 members of the community and a random sample of 74 out-patients with affective symptoms were interviewed using the Present State Examination (PSE) and Life Events and Difficulties Schedule (LEDS) of Brown and Harris. The survey has resulted in many publications. The present paper summarises its aims, methods and results. PMID- 1745924 TI - The 12-year clinical course of schizophrenia. AB - A sample of 46 schizophrenic night-clinic patients (N patients), was matched with a sample of 46 hospital patients (H patients) for diagnosis, age, and sex. They were followed up from 1971/73 until 1983 on the basis of a personal interview and by review of all the case histories and other documents. Their average age at the time of the follow-up examination was 40 years. The average duration of the illness was 18 years in the night-clinic patients and 15 years in the hospital patients. Seven of the 46 N patients (1.4% per year) and two of the 46 H patients (0.4% per year) died during the 12 years. Of the surviving patients one-third had inconspicuous psychopathology. In one-fifth, psychopathology was only conspicuous to a psychiatrist. Only in one-quarter was it very conspicuous even to the layman. The N patients had already shown clearer signs of a chronic, insidious clinical course during the first four years of their illness than the H patients. Although substantially fewer were hospitalised at the time of the follow-up examination (17.6% cf 28.6% respectively), far more of them were receiving either outpatient or semi-inpatient care. Unsatisfactory social integration was revealed, their strong tendency to self-isolation and their inadequate work rehabilitation: 71.8% of the N patients and 62% of the H patients were dependent on a disability pension, and only 15.4% of the N patients and 20% of the H patients were employed at work in keeping with their training and experience. Just under half of the patients were living alone. Some 30-40% of them had no contacts with friends or acquaintances. Predictors of a somewhat favourable clinical course included an acutely phasic course during the first few years of the illness, a low level of parental education, and a greater age at the time of the manifestation of the illness. In particular, patients whose illness ran an acute phasic course during the four years after onset had less lengthy hospitalisations in the second stage of the clinical course than patients exhibiting signs of chronicity in the early stage. PMID- 1745925 TI - Subjective stress in schizophrenic patients. AB - The relationship of major life events and daily stressors to subjective stress was investigated in outpatients suffering from schizophrenia. Daily stressors or hassles were found to be more predictive of subjective stress than were major life events. These findings were not influenced by whether a cross sectional or prospective analysis was used. The implications for future research on stress and schizophrenia are discussed. PMID- 1745926 TI - Transfer between psychiatric hospitals: symptom, social function and patient attitude changes in long-term patients. AB - This study followed up a ward group of long-term, mainly schizophrenic patients after transfer from Bexley Hospital, a large institution in South East London, to small purpose built rehabilitation unit in a distant hospital, and used a matched control group of patients remaining in Bexley Hospital for comparison. There was no pattern of symptomatic improvement or deterioration with time in either group, but social functioning and behaviour did improve in those transferred. The patients transferred were well informed about the process, became more favourable about the medical advice offered to them but remained sure, as did patients in the control group, that they wanted to leave hospital eventually. We suggest that the successful transfer of patients between hospitals must involve clear information to prepare patients and relatives, the consent of patients, staff enthusiasm, the provision of a full range of services after transfer, including occupational therapy, and staff continuity. PMID- 1745927 TI - The Ryle Marital Patterns Test as a predictor of symptoms of anxiety and depression in couples in the community. AB - The associations between marital relationships, as measured by the Ryle Marital Patterns Test, and symptoms of anxiety and depression as measured by the Interval General Health Questionnaire (I-GHQ), were assessed in 98 married couples in the community. Logistic regression analyses showed that symptoms of anxiety and depression in wives were best predicted by low ratings of affection exchange. Occupational class interacted with husbands' affection ratings, suggesting that in the nonmanual class only lower affection ratings were significantly associated with more symptoms. Anxiety in men was best predicted by low affection ratings while depression was best predicted by unemployment, by an affection discrepancy score indicating that more affection is given than received, and by a marriage which was rated as relatively more wife-dominated by wives and as relatively more husband-dominated by husbands. PMID- 1745929 TI - Occupational stress among mental health professionals. The relationship between work and recreational pursuits. AB - A sample of 111 medical and allied staff in a large child and adolescent psychiatric hospital responded to a survey assessing work- and leisure-related attitudes. Gender, marital status, parenthood, and length of employment were among the demographic variables found to be associated with various facets of occupational stress and job satisfaction. Men were somewhat more stressed, complained more about their relationships with coworkers and displayed greater 'negative spill' than women; Married employees were particularly susceptible to the adverse effects of work; Parenthood had little effect on work-related stress, although there is some indication that being a mother prevented one recuperating as effectively as desired during leisure-time; and tenure of employment at the hospital was related to increased feelings job pressure without affecting job satisfaction levels, and to lower levels of career motivation. The implications of these findings are discussed: Suggestions are provided for improving working climate and job satisfaction amongst mental health professionals. PMID- 1745928 TI - Factors affecting service utilization for depression in a white collar population. AB - The present study examines rates of mental health service utilization among depressed individuals in a large white collar cohort. Clinical and psychosocial features of a recent depressive episode, as well as preexisting psychiatric and psychosocial characteristics, are examined for their ability to distinguish between individuals who (a) did and did not seek help during their episode and (b) chose to consult one professional source rather than another. Results showed that approximately one-third of the sample sought professional help. Respondents consulting mental health specialists were more clinically impaired and had poorer work performance and fewer psychosocial assets than both those consulting nonpsychiatric physicians and those seeking no help. Respondents in the latter two groups were indistinguishable from one another on many of the assessed variables. PMID- 1745930 TI - [High-resolution CT of the lung]. PMID- 1745931 TI - [Radiologic diagnosis of pulmonary embolism]. PMID- 1745932 TI - [The therapeutic modification of euthyroid goiter by thyroid nodule changes using thyroid hormones]. PMID- 1745933 TI - [Diagnosis and interventional aspects in cystic lesions of the liver]. PMID- 1745934 TI - [The potentialities of MRT in radiation planning for rectal cancer]. PMID- 1745935 TI - The Human Genome Project--does South Africa have a role to play? PMID- 1745936 TI - [A look into the future of inter-species organ transplantation]. PMID- 1745937 TI - Malabsorption of carbohydrate foods by urban blacks. AB - Prevalences of non-infective bowel diseases are very low in South African urban blacks compared with the white population. In seeking elucidation, using breath hydrogen measurements in series of black and white subjects, small-bowel transit time was determined, and the malabsorption of maize, wheat, and rice investigated. Median transit times in both ethnic groups were similar. Rice was fully, but wheat incompletely absorbed by both groups. Maize, the staple food of blacks, was incompletely absorbed by them, although completely absorbed by the white subjects. Carbohydrate consumption is high in the black population (60-65% of total energy intake). It is probable that in blacks, despite their now eating a low-fibre diet, an expected increase in large-bowel diseases has been inhibited in part by the protective mechanism of fermentation of malabsorbed maize and wheat. PMID- 1745938 TI - Glycaemic responses to different carbohydrate foods in healthy and diabetic blacks in Soweto. AB - Diabetes mellitus is uncommon in rural southern African blacks. With urbanisation and lifestyle changes, incidence rises to that in western populations. To assess associated changes in carbohydrate metabolism, glycaemic responses to glucose, refined maize, refined rice and bread were studied in 8 healthy and 8 non-insulin dependent diabetic urban blacks. Additionally, in the healthy group serum insulin responses were measured. In the healthy, maize (the staple food of blacks) elicited the highest glucose response (207 mmol/l/min) and bread the lowest (107 mmol/l/min). The glycaemic indices of maize and glucose were similar. Serum insulin responses to maize were significantly lower than that of bread at 90 minutes (maize 66 muU/ml; bread 93 muU/ml; P = 0.02). In diabetics, maize and glucose elicited similar glycaemia (928 mmol/l/min and 921 mmol/l/min respectively). The high glucose response to maize could relate to its processing and physical form. The low insulin secretion could be due to inadequate stimulation by the 'entero-insular' axis. Moreover, variability in glucose insulin responses could stem from ethnic or genetic reasons. In the dietary management of black diabetics, refined maize should be replaced by other cereals. PMID- 1745939 TI - Outpatient compliance with theophylline and phenytoin therapy. AB - Poor compliance with prescribed medication is a significant problem in chronic disease states and is often responsible for the apparent failure of therapy. The determinants and extent of non-compliance are commonly incorrectly perceived by doctors. During routine therapeutic drug monitoring of epileptic and asthmatic outpatients at a local day hospital, non-compliance was identified as a significant problem. A compliance study was conducted on 80 epileptic and asthmatic patients to determine the nature and extent of this problem. Non compliance was measured using four different methods, which were then compared using chi 2 tests. Overall incidence of non-compliance was found to be 63%. Age, sex, standard of education and duration of disease were found to have no association with non-compliance. The most clinically significant finding was that almost half the patients were unaware of the necessity of taking their medication on a continuous basis. No significant differences existed between assessing non compliance using tablet counts, patient interview and clinic attendance, whereas the method using blood levels gave significantly different results from all the other methods used. PMID- 1745940 TI - [Expenditures on medicines at provincial hospitals in the Cape. A comparative analysis from 1982-1989]. AB - Total expenditure on medicines at various hospitals within the Cape Provincial Administration (CPA) branch of hospital and health services has increased minimally in relation to the consumer price index of 1982 (CPI-1982). However, the calculated cost of medication per patient unit differed greatly between the hospitals studied. Calculations based on CPI-1982 showed the increase at Tygerberg Hospital (TBH) to be 24.3% lower than the increase in CPI. Based on the CPI-1985, the increase at TBH was 4.01% higher than the CPI increase. At another academic hospital the increase based on CPI-1982 was 35.78%, at two large non academic hospitals it was 45.31% and 17.71% respectively, and for the CPA as a whole it was 18.83%. Direct comparisons of cost per patient unit between hospitals are inappropriate, because of the varying patient profiles and consequent differences in required treatments. However, a cost awareness programme seems to have been at least partially responsible for the variance in cost increase at TBH. A more intensive and sustained programme to encourage cost awareness in the prescribing of medicines is called for. PMID- 1745941 TI - Market fallacies in health economics. AB - Serious methodological errors that plague studies in health economics are examined with the focus on misconceptions about the nature and functions of markets. The belief that market economics do not apply to the medical marketplace involves circular reasoning that treats man-made laws and regulations as though they were unchangeable laws of nature. Arguments against the market provision of health care are questioned and the 'information gap' problem is shown to be aggravated, if not caused, by regulations that prevent normal information flows in the market. Similarly, the contention that health care insurance pushes up costs is criticised on the basis of both theory and empirical evidence. The apparent failure to contain costs may be blamed on legal restrictions, government spending and pressure from medical associations. Confusion between normative theory and positive theory is also examined. PMID- 1745942 TI - Women doctors in South Africa. A survey of their experience and opinions. AB - The proportion of women entering medical school has increased at some faculties but remains at around 20% at others. A postal survey of 2,626 women on the Medical Register of the South African Medical and Dental Council was conducted to investigate aspects related to their work. Fifty-five per cent responded, with a possible bias towards older doctors and graduates from Afrikaans-language faculties. Although a significant majority (86.5%) are in practice, about one third (33.4%) are employed part-time and nearly one-third (29.4%) reported that they had experienced an interruption of their careers for periods of more than 5 years. Major factors relating to this wastage of medical resources identified by this study were the women's dual responsibility at home and at work, the one-time joint taxation system and discrimination in the workplace, in particular with regard to housing loans. Few women find their way into specialist practice (10.8%) [corrected], although 68.2% indicated that they would have liked to specialise. Home responsibilities (48.2%) and the structure of the curriculum (31.5%) were the commonly reported difficulties experienced with further study. In addition, the lack of part-time training and the geographical location of such facilities also played a role. PMID- 1745943 TI - The MEDUNSA Stroke Data Bank. An analysis of 304 patients seen between 1986 and 1987. AB - Stroke is a major cause of mortality and morbidity in black Africans. The MEDUNSA Stroke Data Bank (MSDB) was established in 1984. Its goal is to gather data on all aspects of cerebrovascular disease in South African blacks, and it is supported by modern investigative techniques such as computed tomography (utilised in 82.2% of cases). The majority of the patients (71.2%) had cerebral infarction. Certain features, such as the importance of hypertension and increasing age as risk factors, were found to be similar to Western stroke populations; also, probable or definite cardiac source for cerebral embolism was present in 46% of the patients. In contrast, however, other features, such as transient ischaemic attacks, peripheral vascular disease, coronary artery disease and lacunar strokes, occurred far less frequently than is reported in Western patients. It is hoped that the MSDB will lead to a better understanding of cerebrovascular disease in blacks and possibly to in-depth comparative studies of the ubiquitous problem of atherosclerosis. PMID- 1745944 TI - Real-time sector compression ultrasonography v. contrast venography in femoropopliteal thrombosis. AB - Compression ultrasonography with a 5 MHz sector transducer was compared prospectively with contrast venography in 61 patients for the diagnosis of deep vein thrombosis (DVT) in the femoropopliteal segment (63 legs). The ultrasonographic procedure was found to be sensitive (84%) and specific (100%) in diagnosing femoropopliteal thrombosis. The results using a sector transducer are comparable with results obtained from the use of linear transducers. The wide availability of 5 MHz sector transducers in radiology departments makes compression ultrasonography a widely applicable alternative to contrast venography for diagnosis of DVT of the femoropopliteal segment. The procedure is less costly, less invasive and less time-consuming than contrast venography. PMID- 1745945 TI - Sacral nerve root entrapment demonstrated on computed tomography--'the winking ogre'. AB - Pictorial analogies are a descriptive modality often employed to convey radiological (as well as clinical and pathological) appearances. Examples of this useful descriptive device abound and many anatomical terms take their origin from such analogies. The cauda equina (horse's tail) and the uvula (grape) are but two classic examples. A radiographic appearance resembling a 'winking ogre' on computed tomography of the lumbosacral junction is described. This appearance is encountered in cases scanned following myelography, where one of the (left or right) first sacral nerve roots is compressed by herniated disc material. PMID- 1745946 TI - Evaluation of various laboratory techniques to diagnose Helicobacter pylori in patients with upper gastro-intestinal tract symptoms. AB - Helicobacter (Campylobacter) pylori is strongly associated with type B gastritis. The detection of H. pylori, which entails histological examination and culture of gastric biopsy specimens, takes several days. There has been much interest in developing more rapid tests, including non-invasive ones. Using histology and/or culture as the 'gold standard', several methods to detect H. pylori were compared and evaluated. The organism was detected in 84 of 100 consecutive patients attending the Gastrointestinal Unit of King Edward VIII Hospital for upper gastrointestinal tract endoscopy. Histological examination was the most sensitive (98%) and specific (100%) method used in detecting H. pylori in gastric biopsy specimens. An enzyme-linked immunosorbent assay to detect specific IgG antibodies to whole H. pylori organisms is a moderately sensitive (82%), non-invasive method but it is nonspecific (38%). Although culture was specific (100%), it was less sensitive (68%) than histological examination. The 'conventional' urease assays must be performed under controlled conditions (37 degrees C) for optimal results (sensitivity, 71%). PMID- 1745947 TI - Impact of a measles immunisation campaign on measles admissions to a Natal hospital. AB - During May and June 1990, a national mass measles immunisation campaign was undertaken in South Africa. This study is an assessment of the impact of the campaign on measles admissions to a provincial referral hospital that has specifically designated wards for children with communicable diseases. Data from the measles ward admissions book for the 18 months before the campaign (1 January 1989-30 June 1990) and 6 months after the campaign (1 July 1990-31 December 1990) were compared. Since the campaign, the average number of measles admissions has declined by 64.4% from 87 to 31 per month (P less than 0.01). Before the campaign, 21.3% of measles patients admitted were aged 7-9 months compared with 27.6% after the campaign, highlighting the urgent need to improve the measles vaccination coverage in this age group. An analysis of the geographical source of patients showed that measles continued to occur after the campaign in most of the areas where it existed before the campaign. It is concluded that important gains have been achieved by the campaign. These will be rapidly eroded and epidemics of measles may occur if measles vaccination efforts wane and slump back to pre campaign levels. It is important to capitalise on the momentum generated through the campaign by continuing to support efforts of existing health care services to improve and maintain high levels of measles immunisation coverage. PMID- 1745948 TI - Botshabelo's vaccination survey. AB - This community-based survey evaluates vaccination coverage of small children and socio-economic status of their households in a randomly selected sample of a black South African township. It reveals a poverty-stricken community, where only 19% of the children surveyed were fully vaccinated. It is suggested that expansion of health infrastructures together with a co-ordinated strategy of immunisation would result in a spectacular increase in vaccination coverage. PMID- 1745949 TI - Reproductive health care in the Gelukspan Health Ward. AB - Reproductive health care, namely family planning, antenatal care (ANC), labour care and postnatal care, was studied in the Gelukspan health ward of Bophuthatswana in 1985-1986. Only a minority of the women interviewed (20%) had planned their last pregnancy, but most had attended for ANC (93%) and had had supervised deliveries in a hospital or clinic (80%). Most (97%) knew of modern methods of fertility control but only a minority (37%) were using them. Planned pregnancies were more likely to be reported by married women (73% of 37 v. 9% of 173; P = 0.0000) who left school at an earlier age (16.0 +/- 5.9 years v. 17.0 +/ 3.9 years; P = 0.0462). If unmarried, women who had planned their pregnancy were more likely to be maintained by the father of the child (15% v. 4%; P = 0.0134). They were also less likely to have left school because of the pregnancy (20% v. 50%; P = 0.0001). Unmarried women with supervised deliveries are more likely to have financial support from the father of the child. Maternal school education is positively related to attendance for ANC, attendance for supervised labour and utilisation of modern methods of fertility control. There seems to be an intricate relationship between the different outcomes measured. ANC attenders were more likely to have supervised deliveries. Both groups were more likely to start attending for child health care earlier and more frequently. Our results are discussed. PMID- 1745950 TI - Early life nutrition in the Gelukspan Health Ward. AB - Breast-feeding, supplementary feeding and weaning practices as well as nutrition during the second year of life were studied in 210 black primiparas, who had cared for their own children through the first year, in a poor, one-crop (maize) rural area in Bophuthatswana. The sampling strategy was similar to the one recommended by UNICEF for assessment of vaccination coverage. Only 1 child had never been breast-fed and 60% were still breast-fed at the time of the interview during the second year of life. A number of factors were detected that seem important determinants of breast-feeding behaviour, e.g. marital status and level of formal education. Early supplementary feeding and early weaning were identified as major problems. Children were weaned onto commercial feeds or low energy-dense staples, and there was also an obvious lack of energy-dense foods (e.g. butter, coconut oil) during the second year of life. Some determinants of these practices were recorded. The data have implications for the health services and should influence social and educational policy for the area. If properly implemented, the recommendations could result in significant financial saving for the study population. The health services should promote appropriate nutritional education, starting with antenatal care, early and frequent attendance at child health services should be encouraged and education concerning nutrition should be strengthened, and health education should encourage prolonged breast-feeding, discourage the use of commercial weaning foods, and encourage the use of natural multimixes (e.g. bananas, beans, cooking oil) for weaning. The importance of energy-dense foods should be emphasised to mothers and to health workers. PMID- 1745951 TI - Human T-lymphotropic virus type I-associated myelopathy. A case report. AB - Tropical spastic paraparesis (TSP) has been reported from various parts of the world for several decades. Recently reports have emerged from Japan and also countries in tropical zones associating endemic TSP with abnormally high titres of antibodies to human T-lymphotropic virus type I (HTLV-I). Data indicate that this lymphotropic retrovirus is neuropathogenic, either by direct invasion or via immunopathological mechanisms. A South African man is described who met the diagnostic criteria of TSP. Both serum and cerebrospinal fluid were antibody positive for HTLV-I. It is possible that HTLV-I infection may be implicated in the 'myelopathies of undetermined cause' that form a substantial subgroup of spinal cord disease occurring in black South Africans. PMID- 1745952 TI - Severe fetal tachycardia after administration of hexoprenaline to the mother. A case report. AB - A fetus developed extreme supraventricular tachycardia (210/min) after intravenous hexoprenaline 10 micrograms was administered to the mother for intrapartum fetal distress. Urgent caesarean section resulted in the birth of a male baby with a reduced Apgar score; the infant survived after being ventilated for 24 hours. PMID- 1745953 TI - Haemostasis by angiographic embolisation in exsanguinating haemorrhage from facial arteries. A report of 2 cases. AB - Life-threatening exsanguinating haemorrhage from arteries of the face following trauma is uncommon. When it occurs it is often located in the relatively inaccessible parts of the vessels and requires deep face or neck exploration and ligation of the main feeding vessel. The procedure requires expert head and neck vascular surgery performed under general anaesthesia, which is often not suitable in these haemodynamically unstable patients. In addition, surgery is often rendered more difficult by the associated post-traumatic swelling and disfigurement. Because of these considerations, angiographic embolisation of the bleeding vessels was performed as an alternative to surgical exploration. This report illustrates its use in achieving haemostasis in 2 patients. PMID- 1745954 TI - Tertiary role of critical care in academic hospitals. PMID- 1745955 TI - Danger of inhaling trichloro-ethane. PMID- 1745956 TI - Innovative medicine? PMID- 1745957 TI - Cognitive recovery correlates with long-term increases of cerebral perfusion after head injury. AB - Prospective measurements of cerebral blood flow (CBF) and Cognitive Capacity Screening Examination (CCSE) were obtained following head injury among 42 patients for a mean total follow-up interval of 10 years. Clinical data obtained at the time of injury and detailed neurological examinations at each follow-up visit were correlated with serial CBF and CCSE scores. Comparisons of the group of patients who cognitively improved (n = 32) were made with the group that did not (n = 10). Of the total group, 76% showed cognitive improvements for as long as 10 years after injury, with CBF increases toward normal. Predictors for long term cognitive improvements include: higher initial Glasgow Coma Scales, earlier recovery from coma, absence of signs of brain stem injury, and improvements of cerebral perfusion and autoregulation. Failure to improve correlated with low initial Glasgow Coma Scales, signs of brain stem injury, and persistent impairments of cerebral perfusion. PMID- 1745958 TI - Perioperative complications of encephalo-duro-arterio-synangiosis: prevention and treatment. AB - We performed encephalo-duro-arterio-synangiosis on 169 sides of 81 Moyamoya and 8 non-Moyamoya patients in the past 10 years. The advantage of this operation is its minimal operative invasion, giving rise to few operative complications. During 10 years of practice, however, we encountered some perioperative problems. Perioperative cerebral infarction of varying severity was seen in six Moyamoya patients. Severe hyperventilation with crying was the main trigger of infarction. Two patients developed wound infection with Gram-negative rods. Removal of an infected bone flap was necessary. One Moyamoya patient developed malignant hyperthermia during the operation. One acute epidural hematoma necessitated an emergency hematoma removal. Five patients showed a temporary aggravation of involuntary movements. Prolonged mild fever and temporary and limited hair loss around the wound were often observed. Cases and their treatment are presented with discussion of preventive measures. PMID- 1745959 TI - Anatomical variations of the straight sinus on magnetic resonance imaging in the infratentorial supracerebellar approach to pineal region tumors. AB - Anatomical variations of the straight sinus (SS) were examined on magnetic resonance imaging (MRI) in 108 control cases and five cases with a pineal region tumor. The data of the latter were compared with the operative findings in the infratentorial supracerebellar approach. In the 108 control cases, the length of the SS was 51 +/- 5.2 mm. The angle of the SS to the nasion-tuberculum sellae line, the tuberculum sellae-inion line, and the nasion-inion line was 51 +/- 6.7 degrees, 44 +/- 5.0 degrees, and 47 +/- 5.0 degrees, respectively. The SS was inclined 1.4 +/- 4.5 degrees posteriorly to the bregma-inion line. The anatomical relationship between the SS and the corpus callosum was subgrouped into three types: in the common type (63%), the extended line of the slope of the SS is tangential to the upper aspect of the splenium of the corpus callosum; in the high-angle type (26%), the extended line is far above the tangent line; and in the low-angle type (11%), the extended line is far below the tangent line. The operative field was restricted by the steeply inclined tentorium in the case of the high-angle type, and the tumor was located much lower than the direction of the operative approach. In contrast, the tumor was easily exposed in the center of the wide operative field in the cases of low-angle type. The present study suggests that the preoperative MRI analysis of the angle of the SS is indispensable before taking the infratentorial supracerebellar approach to the pineal region tumors. PMID- 1745960 TI - Reconstruction of the skull base using a silicone plate during transsphenoidal surgery. AB - Our operative experience of reconstruction of the skull base using a silicone plate during rhinoseptoplastic transsphenoidal surgery is described. A suitably shaped plate can be easily and quickly made from a large silicone block of the type that is widely used in cosmetic surgery. The plates can be distinguished on magnetic resonance images postoperatively. We consider that this technique is of use not only for repairing the sellar floor, but also for closing a wide defect of the skull base. PMID- 1745961 TI - Intracranial cerebrovascular vasa vasorum associated with atherosclerosis and large thick-walled aneurysms. AB - Atherosclerotic plaques that develop in the extracranial circulation are usually extensively vascularized by vasa vasorum. However, human vasa vasorum associated with intracranial atherosclerosis has not been adequately addressed. Anterior and posterior circulation specimens from fresh autopsy material were studied under the magnification of a dissecting microscope and proliferative vasa vasorum was found to be frequently associated with intrinsic atheromatous plaques. Vasa vasorum associated with an incidental large aneurysm supports the radiological literature demonstrating that many large and giant thick-walled aneurysms exhibit vascularized walls on contrast computed tomography scans. This information may aid in the preoperative assessment and possible repair of these aneurysms. PMID- 1745962 TI - A national survey of neurosurgical care for penetrating head injury. AB - We report results of a survey on the management patterns of penetrating head injury (PHI). American neurosurgeons (N = 2969) were asked to participate in a mail survey. One thousand one hundred twenty-eight responded, providing detailed information about their practices, their opinions concerning diagnostic testing, nonoperative therapy, and surgical debridement for PHI. Although there was agreement on some areas of management and care, including the use of computed tomography scanning, antibiotics, anticonvulsants, and a few surgical indications/contraindications, there was wide variation on a significant number of points. These included testing for coagulopathy; use of corticosteroids, intracranial pressure monitoring, and barbiturate coma; and surgical indications including debridement of contusions, removal of fragments, location of injury, and Glasgow Coma Score 5-8. Many nonoperative decisions were influenced by the presence of neurosurgical residents, whereas the decision to operate was based primarily on judgment of patient salvageability. This survey uncovered disagreement on several crucial issues in the care of patients with penetrating head injury and the need for continued research in this area of patient care. PMID- 1745963 TI - New division of neurosurgery at Toronto Hospital. PMID- 1745964 TI - Benign nasal polyposis presenting as an intracranial mass: case report. AB - An interesting case of benign nasal polyposis with intracranial extension and subsequent abscess formation is described. Its diagnosis and treatment are presented and the pathology is demonstrated. The literature related to this rare disease process is discussed in detail. PMID- 1745965 TI - Intracranial lipoma in the medulla oblongata. AB - Intracranial lipoma in the medulla oblongata has been rarely reported. Only two cases have been documented in the literature. This report concerns a patient who complained of nuchal soreness and an unstable gait for 6 months. An olivelike lipoma, arising from the posterior aspect of the medulla oblongata and embedded in the lower cranial nerves, was found at suboccipital craniectomy and posterior laminectomy of C1-2. Partial removal of the lipoma was performed for decompression; radical removal would have been hazardous. The clinical symptoms subsided postoperatively. The computed tomography scan and magnetic resonance image proved useful for properative diagnosis. PMID- 1745966 TI - Hemangioma of the temporalis muscle: case report and review of the literature. AB - A 51 year-old man presented with a 10-year history of a painless, slowly growing mass (35 x 25 x 15 min) in the right temporal fossa. The T1-weighted image on magnetic resonance imaging demonstrated a partial, low-signal intensity lesion with high intensity in the lower part and significant enhancement with contrast medium. The tumor, which lay within the temporal muscle, was totally excised, and histological examination confirmed the lesion to be an intramuscular, cavernous type of hemangioma. The therapeutic options are described. PMID- 1745967 TI - Abdominal cyst formation following ventriculoperitoneal shunt in a case of hydrocephalus due to cryptococcal meningitis. Case report: completely cured by surgical removal of the cyst and treatment with a newly developed anti-fungal drug (Difulcan). AB - A 54-year-old woman was admitted to the hospital for evaluation of meningitis. Tuberculous meningitis was suspected initially because of general findings and a high adenosine deaminase activity (ADA) value in the cerebrospinal fluid. Administration of antituberculous drugs was not effective. Computed tomography scanning revealed progression of ventricular enlargement. A ventriculo-peritoneal shunt was placed upon diagnosis of hydrocephalus due to meningitis. The presence of a large abdominal cyst formation was demonstrated. Cryptococcus was detected in the cyst fluid, leading to a diagnosis of cryptococcal meningitis. Intravenous administration of fluconazole (400 mg/day) was begun. Excision of the cyst was performed when Cryptococcus was no longer detected in the cyst fluid. The patient recovered uneventfully. PMID- 1745968 TI - Difficult to determine the origin of neuromas in jugular foramen. PMID- 1745969 TI - Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma. AB - From November 1979 to July 1986, 52 patients (27 women and 25 men; median age 52 years) with advanced adrenocortical carcinoma entered a prospective, nonrandomized study evaluating moderate-dose mitotane and doxorubicin hydrochloride (Adriamycin). Thirty-two tumors (62%) were well differentiated and evidence of hormone production was present in 24 patients (46%). Patients with well-differentiated or functional tumors received mitotane, 6 gm daily; patients for whom mitotane failed or those with poorly differentiated, non-hormone producing tumors received Adriamycin, 60 mg/m2 every 3 weeks. Initially, 36 patients were treated with mitotane and 16 patients with Adriamycin. Eight patients (22%) responded to mitotane and three (19%) responded to Adriamycin. No response was noted in the 15 patients for whom mitotane failed and who then received Adriamycin. Severe toxicity occurred in 36% of patients who received mitotane and in 26% who received Adriamycin. Overall median survival after onset of treatment was 14 months. We conclude that mitotane or Adriamycin used initially can induce tumor regression in about 22% and 19% of selected patients, respectively. However, Adriamycin is ineffective as second-line chemotherapy for patients with well-differentiated or functioning tumors for whom mitotane is ineffective. PMID- 1745970 TI - Incidentally discovered adrenal tumors: an institutional perspective. AB - With the aim of developing guidelines for investigation and management of adrenal incidentalomas, 2066 patients with adrenal masses were analyzed from a total of 61,054 computerized tomographic (CT) scans done from 1985 through 1989. Excluding patients with previous or concurrent malignancies, adrenal tumors localized after biochemical documentation of disease, and adrenal nodules less than 1 cm, 259 patients (0.4%) remained for analysis. Added to these were 83 patients (total 342) in whom the adrenal tumor had been found elsewhere before referral. There were 136 men and 206 women with a mean age of 62 years. Tumor diameter ranged from 1 to 11 cm (average 2.5 cm). Studies to evaluate biochemical hyperfunction were performed in 172 patients (50%), 2 of whom were found to have cortisol producing tumors and 5 pheochromocytomas. Histologic proof of diagnosis was obtained in 55 patients at the time of adrenalectomy. Malignancy was discovered in five patients (four primary and one metastatic), the smallest malignant tumor measuring 5 cm. In the 287 patients without histologic diagnoses, a minimum of 1 year of clinical follow-up was obtained in 251 (88%), including repeat CT scan in 156 (54%). None of these patients had clinical or biochemical adrenal abnormalities. We suggest (1) biochemical screening in patients with incidentalomas larger than 1 cm, (2) surgical excision of tumors 4 cm or greater, and (3) a comparison CT scan approximately 3 months after diagnosis in patients with tumors less than 4 cm in whom observation has been chosen. PMID- 1745971 TI - Primary hyperparathyroidism during pregnancy. AB - Historically, primary hyperparathyroidism during pregnancy was associated with significant risk of maternal morbidity and fetal death. Maternal hypercalcemia results in fetal hypercalcemia, leading to suppression of fetal parathyroid gland function. Neonatal hypocalcemia with tetany is a common occurrence after birth when maternal calcium flow is interrupted. From 1930 to 1990, 109 cases of women with primary hyperparathyroidism associated with pregnancy have been reported, 39 of whom were treated surgically before delivery. Although fetal mortality rates for medically treated women have improved, fetal morbidity continues to remain higher than in women who undergo surgical treatment of parathyroid disease during pregnancy. Of 850 patients treated surgically for primary hyperparathyroidism since 1960, 12 were pregnant. Four of the patients were treated medically during pregnancy and underwent surgery after delivery; all four infants had neonatal hypocalcemia and tetany. The remaining eight patients were treated surgically during pregnancy: six in the second trimester and two (one with associated pancreatitis and one with hypercalcemic crisis) during the first trimester. There was no fetal or maternal morbidity or death in the surgical group. Parathyroid adenomas were present in 10 of the patients, hyperplasia in one, and parathyroid carcinoma in one. The management of maternal primary hyperparathyroidism diagnosed during pregnancy should be based on the patient's symptoms and severity of disease. Hyperparathyroidism characterized by progressive symptoms should be treated surgically, preferably during the second trimester. Symptom-free patients and those with mild hypercalcemia diagnosed in the third trimester may be managed medically, postponing operation until after delivery. PMID- 1745972 TI - Usefulness and limits of quick intraoperative measurements of intact (1-84) parathyroid hormone in the surgical management of hyperparathyroidism: sequential measurements in patients with multiglandular disease. AB - This study was designed to assess whether reliability of quick intraoperative assay of intact (1-84) immunoreactive parathyroid hormone (iPTH) could allow us to quit after removing one (or several) enlarged parathyroid gland(s) and obtaining a normal iPTH level. Intact iPTH was assayed during surgery before removal of enlarged parathyroid gland(s) and 5, 10, and 20 minutes afterward. Forty-seven patients entered the study: 40 with primary hyperparathyroidism (32 with uniglandular disease and eight with multiglandular disease) and seven with secondary hyperparathyroidism; all underwent bilateral neck exploration. Among 32 patients with uniglandular disease, five had normal basal intraoperative levels, 25 demonstrated a clear-cut drop from supranormal to normal levels, and two had elevated levels. Among the eight patients with multiglandular disease, two had undetectable levels and two had normal levels after removal of the first enlarged gland. The seven patients with secondary hyperparathyroidism demonstrated a decline in PTH levels, suggesting hormone clearance similar to that of patients with primary hyperparathyroidism. In conclusion, quick intraoperative assay with intact (1-84) iPTH (1) is not hampered by renal insufficiency, (2) may overlook a second enlarged gland after removal of a first adenoma and obtaining normal iPTH levels, and (3) should not be used as a substitute for bilateral neck exploration. PMID- 1745973 TI - Relevance of vitamin D metabolite concentrations in supporting the diagnosis of primary hyperparathyroidism. AB - We compared the relationships between 25-hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D] levels in patients with primary hyperparathyroidism (PHPT) and 38 volunteer blood donors. There was no significant difference in mean 25(OH)D levels between patients with PHPT (34 +/- 21 nmol/L; n = 21) and the donor samples (41 +/- 19 nmol/L; n = 38). Serum 1,25(OH)2D levels were higher in the patients with PHPT compared with the donors (122 +/- 61 pmol/L vs 56 +/- 41 pmol/L; p less than 0.001). The 95th percentile 1,25(OH)2D value for the donors was exceeded in 65% of the patients with PHPT. There was a significant correlation between serum 1,25(OH)2D versus 25(OH)D in the patients with PHPT (r = 0.50; p less than 0.05) but not in the donors (r = 0.02). We conclude from the distinct elevation in 1,25(OH)2D levels in the majority of our patients with PHPT that the concentration of this parathyroid hormone-dependent hormone can be of critical value in corroborating the diagnosis of PHPT. PMID- 1745974 TI - The role of circulating N-terminal parathyroid hormone fragments in the early postparathyroid adenomectomy period. AB - Calcium metabolism and hormonal control after parathyroid adenomectomy are poorly understood. During the first postoperative hours, biologically active intact parathyroid hormone (PTH) (hPTH 1-84) levels are subnormal and, in spite of down regulation of PTH peripheral receptors (caused by hypercalcemia before surgery), total and ionized calcium concentrations are maintained in the normal range. Serum samples from 20 patients with primary hyperparathyroidism were collected in the immediate preoperative period and 4 and 48 hours after excision of one parathyroid adenoma. Total and ionized calcium, intact (iPTH), midregion (mrPTH) specific PTH (hPTH 53-68), and N-terminal PTH (N-PTH) serum concentrations were determined. Levels of N-PTH were obtained with a radioimmunoassay by a modified reverse immunoextraction procedure that measures N-PTH fragments after exclusion of the interfering iPTH. No significant correlation was found between ionized and total calcium, mrPTH, and iPTH. However, total and ionized calcium levels correlated well with N-PTH (r = 0.9999, p = 0.0054, and r = 0.9993, and p = 0.0226, respectively). The data suggest that the relatively moderate decrease in calcium levels, in spite of marked decrease in circulating iPTH during the first postoperative hours, may be attributable to the minimal decrease of the bioactive N-PTH epitope concentrations. We would hypothesize that hPTH (1-34) fragments may play a significant role in regulating serum calcium levels in the early postoperative period. PMID- 1745975 TI - High phosphate diet-induced primary hyperparathyroidism: an animal model. AB - Primary hyperparathyroidism (PHPT) is increasing in incidence and detection, primarily because of the aging of our population and the widespread use of automated serum calcium determination. As a result, a substantial number of "early" cases or "biochemical" PHPT are being detected. The indications for parathyroidectomy in such early cases of PHPT are currently under debate, primarily because of economic issues. These factors underscore the importance of research into the basic mechanisms and natural history of PHPT. We investigated an animal model of diet-induced PHPT that retains two crucial aspects of PHPT: elevation of endogenously produced parathyroid hormone (PTH), accompanied by gross and microscopic changes in the native parathyroid glands. Female Long-Evans rats were divided into six groups of 15 each and fed a control diet (Ca/P of 1:2) or a high-phosphate diet (Ca/P of 1:7) for 1-, 2-, or 3-month intervals. Compared with the control animals, serum PTH levels were elevated at all three time intervals in the experimental group, whereas serum calcium levels were decreased at all time intervals. Serum creatine levels were also elevated at all time intervals, whereas serum phosphorus levels did not change. Parathyroid histopathologic studies demonstrated no change at 1 month, whereas nine of 15 experimental animals showed mild hyperplasia at 2 months and 13 of 14 showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2 and 3 months in the experimental groups. In conclusion, the high-phosphate diet successfully induced the earliest changes of PHPT: elevated PTH levels and parathyroid hyperplasia. However, because renal function was mildly compromised early on, some element of early secondary (renal) hyperparathyroidism may have supervened quickly. Because this model is simple, it may be useful to investigate this complex syndrome further, as well as its natural history and the complications it produces in other organs such as the kidneys. PMID- 1745976 TI - Lithium effects on dispersed bovine parathyroid cells grown in tissue culture. AB - It is not clear whether hypercalcemia and hyperparathyroidism associated with lithium therapy are the result of an unmasking of preexisting disease or a direct effect of lithium on the parathyroid glands. To investigate this phenomenon, parathyroid hormone (PTH) secretion and cytosolic calcium concentrations [( Ca]i) were measured in normal and lithium-treated dispersed bovine parathyroid cells grown in tissue culture and incubated with varying concentrations of extracellular calcium [( Ca]e) (0.5 to 2.5 mmol/L). Results indicate that lithium has two effects on parathyroid secretory response: (1) a decrease in low calcium stimulated PTH release and (2) a potentiation of PTH release at physiologic concentrations of extracellular calcium. [Ca]i was assessed by use of fura-2, a calcium-sensitive fluorescent indicator. Resting [Ca]i levels were unaffected by lithium (103 +/- 13 nmol/L in controls vs 101 +/- 5 nmol/l in lithium-treated cells, mean +/- SE). Subsequent increases in [Ca]i in response to increases in [Ca]e were significantly less in lithium-treated cells, with no difference at maximal [Ca]e. Increases in [Ca]i in response to a submaximal concentration of extracellular magnesium were also blunted in cells pretreated with lithium. In conclusion, our data suggest that, at physiologic calcium concentrations, lithium decreases parathyroid cell sensitivity to changes in [Ca]e, reducing [Ca]i levels and increasing PTH secretory response. PMID- 1745977 TI - Location, incidence, and malignant potential of duodenal gastrinomas. AB - Duodenal gastrinomas are increasingly found at surgery, yet information about their location and characteristics is based on the results of either pooled series or retrospective reviews of small numbers of selected cases. To address these issues we have analyzed the location, incidence, and malignant potential of duodenal gastrinomas in 65 consecutive patients who underwent removal of all tumor as part of a 10-year prospective study to resect gastrinomas in patients with sporadic Zollinger-Ellison syndrome. The primary gastrinoma was located in the duodenum in 24 patients (37%). There were 19 men and five women aged 32 to 69 years (mean 49.4 years), with symptoms for 0.6 to 35 years (mean 7.9 years). Preoperative studies included serum gastrin levels of 114 to 35,798 pg/ml (mean 2060 pg/ml), basal acid output of 7 to 95 mEq/hr (mean 37.6 mEq/hr), and a positive secretin test result in 22 patients. Preoperative imaging studies identified tumor in the duodenal area in 11 patients (46%), but most positive imaging findings were metastatic gastrinoma in lymph nodes, and the primary duodenal tumor itself was identified in only two patients. Portal venous sampling had a localizing gastrin gradient in the inferior or superior pancreaticoduodenal vein in 17 of 23 patients (74%). Each of the 24 patients had a single, small duodenal wall tumor of 2.8 to 10.1 mm diameter (mean 6 mm). Each tumor stained positive for gastrin by immunohistochemistry. Seventeen tumors (71%) were located in the first portion of the duodenum, five (21%) in the second, and two (8%) in the third. Each tumor originated in the submucosa, and 13 (54%) were limited to the submucosa, whereas 11 (46%) were locally invasive, four (16%) extending into the muscularis mucosa and seven (29%) into the muscularis propria. Thirteen patients (54%) had spread to regional lymph nodes, whereas two (8%) had liver metastases. Lymph node metastases were seen with larger duodenal tumors (mean 7.1 vs 5.4 mm; p less than 0.01). The data suggest that a single duodenal wall gastrinoma is a common cause of Zollinger-Ellison syndrome (37%). These small (less than 1 cm) tumors are located in the submucosal layer of the proximal duodenum (92%) and are malignant more often than previously thought (54%). PMID- 1745978 TI - Primary bilateral adrenocortical causes of Cushing's syndrome. AB - Nontumorous primary adrenal causes of Cushing's syndrome are exceedingly rare. Herein we review our results with seven patients in whom there is biochemical evidence of a primary (adrenocorticotropin independent) bilateral adrenal cause of endogenous hypercortisolism. Each patient had low plasma adrenocorticotropin levels. All patients had elevated 24-hour urinary free cortisol levels and 17 hydroxycorticosteroids that were not suppressed by high-dose dexamethasone. Plasma levels of adrenocorticotropin and cortisol were not elevated by ovine corticotropin-releasing factor. No patient had a gradient between petrosal and peripheral adrenocorticotropin levels. No pituitary tumors were detected by magnetic resonance imaging or computed tomography. Five of six patients who underwent iodocholesterol scanning showed bilateral adrenal activity. Computed tomographic and magnetic resonance imaging of the abdomen demonstrated bilateral small adrenal glands in three patients, an adrenal mass in one patient with Carney's complex, and massively enlarged glands in three patients. Each patient underwent bilateral adrenalectomy and was given glucocorticoid and mineralocorticoid replacement. Pathologic examination of four of these bilateral adrenal specimens revealed primary pigmented micronodular adrenocortical disease, with adrenal gland weights between 2.5 and 13.4 gm (mean 5.2 gm). However, the remaining three patients had primary adrenocorticotropin-independent bilateral macronodular adrenocortical disease with adrenal gland weights between 32 and 81 gm (mean 52 gm). Although each of the patients with primary pigmented micronodular adrenocortical disease was cured by bilateral adrenalectomy through a posterior approach, two of the three patients required an anterior approach. We conclude that Cushing's syndrome can arise through two distinct forms of primary bilateral adrenal cortical disease. Computed tomography is important in evaluation of these patients because the size of the adrenal glands influences the surgical approach. PMID- 1745979 TI - Presidential address: Beyond surgery. American Association of Endocrine Surgeons. PMID- 1745980 TI - Thyroglossal duct carcinoma. AB - Thyroglossal cysts are common developmental abnormalities of the thyroid gland. The malignant form of these cysts, however, is extremely rare, with fewer than 100 cases reported since 1915. Here we add 10 cases of malignant thyroglossal cysts, nine women and one man, encountered at M.D. Anderson Cancer Center, based on a retrospective review of 51 recorded cases of thyroglossal cysts between 1950 and 1990. All 10 patients underwent a primary Sistrunk procedure. Histologic findings showed nine papillary and one follicular carcinoma. Based on review of the histopathologic material, four patients required no additional therapy. Five patients underwent total thyroidectomy; three of the five also underwent neck dissection. A single microscopic focus of carcinoma in the thyroid gland was found in only two instances. No evidence of nodal metastases was found. One patient with an abnormal thyroid scan is awaiting further treatment. Based on these findings, the Sistrunk procedure is an effective form of therapy for malignant thyrogloassal cysts. PMID- 1745981 TI - Second operations for "completion" of thyroidectomy in treatment of differentiated thyroid cancer. AB - The role of elective completion thyroidectomy after lobectomy for differentiated thyroid cancers remains controversial. The potential benefit of tumor removal by the second procedure is considered by some to be overbalanced by a prohibitive operative morbidity rate. During a 20-year period at the University of Chicago Medical Center, 26 patients underwent completion thyroidectomy within a 6-month period of the original thyroid operation. This group represents 8% of the 326 patients who underwent surgery during that time for differentiated thyroid cancer (269 papillary and 57 follicular). Of the 26 patients, 18 had papillary and eight had follicular cancers. The average size was 2.5 cm, with 24 of 26 being greater than 1 cm in diameter. At the first operation, 81% of tumors were intrathyroidal. Eight percent had lymph node metastases and 12% manifested local invasion. Tumor was found in eight (31%) of 26 of the reoperative specimens. The incidence of tumor did not vary by histologic type but did differ according to the extent of the original operation. Cancer was found in 50% (three of six) of those who had undergone previous partial lobectomy, in 33% (five of 15) of those after a total lobectomy, and in none of five who had undergone a prior bilateral (although incomplete) thyroid resection. One permanent recurrent nerve injury occurred at the first operation. No additional recurrent nerve injuries or hypoparathyroidism occurred as a result of the second operation. Finally, no disease characteristic of the initial tumor (e.g., size, clinical class, tumor capsular invasion, multifocality, thyroiditis, or extrathyroidal tumor invasiveness) predicted the presence or absence of tumor on the second side. We conclude that completion thyroidectomy is appropriate for patients with lesions 1 cm or greater who have undergone lobectomy or less at the original operation, because 40% of such patients would be expected to have residual cancer. With care, this operation can be performed with minimal morbidity. PMID- 1745982 TI - Genetic markers in thyroid tumors. AB - Tissue from nine patients with malignant tumors and two with benign tumors was cultured briefly before cytogenetic analysis. The tumors included one goiter and one Hurthle cell adenoma, one lymphoma, one medullary carcinoma, two Hurthle cell cancers, and five papillary cancers, varying widely in clinical staging and histologic differentiation. When assessed, DNA content was aneuploid in two of six malignant tumors. Various culture conditions (oxygen levels, dissociation methods, and media) were evaluated; the end points were growth, cell differentiation, and time to first harvest. Clonal aberrations were detected in one of four successfully harvested papillary cancers: they consisted of trisomy 7 and a rearrangement of chromosome 10. The rea (10) seen in 22 of 27 cells involved bands q11-21. Two other papillary tumors and a medullary cancer (a family member with multiple endocrine neoplasia type IIA) showed tetraploidy and nonclonal numerically aberrant cells. A lymphoma and two benign lesions showed no cytogenetic abnormality. The tumor with rea (10) is of special interest because abnormalities of 10q have been reported repeatedly in thyroid tumors, including two cases of papillary thyroid tumors with a structural aberration similar to that of the presented case. This rearrangement could affect the ret-proto oncogene, localized to 10q11.2 which is activated in some papillary thyroid carcinomas. PMID- 1745983 TI - Anaplastic thyroid carcinoma: risk factors and outcome. AB - Anaplastic thyroid carcinoma, in contrast to well-differentiated thyroid carcinoma, has a dismal prognosis, and little progress has been made in improving survival for this disease. We reviewed our experience during a 23-year period to identify risk factors and possible methods to improve outcome. Between 1966 and 1989, 340 patients with thyroid carcinoma underwent operation. Of these, 17 (5%) were undergoing operative treatment of anaplastic or undifferentiated thyroid carcinoma. The female/male ratio was 3.5:1, and mean age at presentation was 63 years. The most common presenting symptoms included neck mass, voice change, or dysphagia. Unusual presentations included symptomatic bradycardia from compression of the vagus nerve and superior vena cava syndrome. Four patients had a history of well-differentiated thyroid carcinoma. Nine patients had been diagnosed or treated in the past for "goiter" or a neck mass, and four patients had concurrent differentiated thyroid carcinoma associated with the anaplastic tumor. Thus 13 (76%) of 17 patients had a previous thyroid disorder, benign or differentiated malignant, and eight (47%) of 17 patients had previous or concurrent differentiated thyroid carcinoma. At the time of presentation, six patients had unilateral true vocal cord paralysis. At operation, 14 patients had local extension of the tumor and four required tracheostomy. Only five of 12 patients showed response to postoperative radiation therapy. Overall median survival was 12 months, and 13 (76%) of 17 patients died. The two patients alive longer than 12 months had only small foci of anaplastic carcinoma in association with well-differentiated carcinoma. Anaplastic thyroid carcinoma is a locally and systemically aggressive disease, with long-term survival seen only in those with well-localized anaplastic tumor. The major risk factor in this series is a history of previous benign or malignant thyroid disease. Because of this, a more aggressive approach to thyroid masses may be warranted. Long-standing goiters or benign nodules should be followed carefully and considered for resection if they grow or do not respond to medical therapy, and total thyroidectomy for malignant disease may obviate the subsequent development of anaplastic carcinoma. This method of early diagnosis and resection of abnormal thyroid tissue seems to be the only method currently available to improve the nearly uniform fatality of this disease. PMID- 1745984 TI - Prognostic significance of calcitonin immunoreactivity, amyloid staining, and flow cytometric DNA measurements in medullary thyroid carcinoma. AB - The proven power of DNA ploidy to predict mortality risk in medullary thyroid carcinoma (MTC) may be weakened when analyzed in conjunction with calcitonin immunoreactivity (CI) and amyloid staining (AS) of tumors. In this study 12 prognostic variables, including DNA ploidy, CI, and AS, were studied in 65 patients with MTC (57 sporadic; mean age 51 years) treated during 1946 through 1970. Cause-specific mortality rates at 10 and 15 years were 15% and 26%, respectively. By univariate analysis, TNM stages III or IV (p less than 0.0001), tumor unresectability (p less than 0.0001), male sex (p = 0.019), negative AS (p = 0.032), and low CI (p = 0.033) were significant predictors of increased mortality rates. DNA ploidy (p = 0.058) and inheritance pattern (p = 0.25) were nonsignificant. By multivariate analysis, only TNM stage, tumor resectability, and AS were independently significant (p less than 0.005). A prognostic model was created, based on presence or absence of these independent risk factors, and four risk groups were defined, capable of predictably defining mortality rates in MTC (p less than 0.0001). The model requires validation in larger series and independent verification by others. However, we believe that a risk-group scheme for MTC based on AS, disease stage, and completeness of tumor resection may have wide applicability and prove relevant to clinicians treating this disease. PMID- 1745985 TI - Effect of tumor necrosis factor on growth and function in FRTL5 cells. AB - Tumor necrosis factor (TNF) is a cytokine produced by inflammatory macrophages and monocytes. FRTL5 cells are a continuous line of functional, nontransformed rat thyroid cells that depend on thyroid-stimulating hormone (TSH) for sustained growth. The following experiments characterize the effects of TNF on growth and differentiated functions in FRTL5 cells. Cells were incubated with different concentrations of TNF (1 to 100 ng/ml), alone or with TSH. FRTL5 cell proliferation was assessed by 3H-thymidine incorporation assays. Differentiated functions were studied by measuring radioactive iodine uptake (RAI) and triiodothyronine (T3) production. TNF inhibited FRTL5 cell growth both in basal conditions and after cells had been exposed to TSH. TNF caused small inhibition of both basal RAI uptake and T3 release but greatly decreased TSH-stimulated RAI uptake and T3 secretion. In summary, TNF appears to affect both growth and differentiated functions in the FRTL5 cell line. Although it is difficult to extrapolate these in vitro results to the human disease state, we postulate that TNF production in septic states may contribute to the pathogenesis of the low T3 syndrome; moreover, locally produced TNF may modulate thyroid function in autoimmune thyroid diseases. PMID- 1745986 TI - Metastatic parathyroid carcinoma: dilemmas in management. AB - The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18 year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients. PMID- 1745987 TI - Results of a prospective strategy to diagnose, localize, and resect insulinomas. AB - Since 1982, 25 consecutive patients with benign sporadic (non-multiple endocrine neoplasia type I) insulinomas have been studied. Most were referred because either the tumor was not identified at the referring institution or the diagnosis was unclear. Each patient suffered severe neuroglycopenic symptoms for a median of 24 months before diagnosis of insulinoma, and 32% had hypoglycemic seizures. Eighteen patients (72%) had a confirmed weight gain. Each patient underwent a supervised fast until 72 hours or the onset of significant neuroglycopenic symptoms (median duration 16 hours), with serum levels of glucose (median 35 mg/dl; range 24 to 46 mg/dl), insulin (median 21 microU/ml; range 11 to 230 microU/ml), C-peptide (median 2.5 ng/ml; range 1.0 to 7.2 ng/ml), and proinsulin fraction (median 55%; range 14% to 86%) measured at the termination of the fast. Preoperative imaging with ultrasonography, computed tomography, magnetic resonance, and angiography visualized tumor in a minority of patients (26%, 17%, 25%, and 35%, respectively); in 48% of patients one or more imaging study results was positive. Selective portal venous sampling for insulin was the most informative localizing test (77% positive; no false-positive results). Tumor was resected for cure in 24 of 25 patients. Intraoperative ultrasonography identified nonpalpable tumor in seven patients and was crucial to the achievement of this high rate of surgical cure. We conclude that the diagnosis of insulinoma can be made by the results of a supervised fast, portal venous sampling is the most sensitive preoperative test for localizing insulinomas, and intraoperative ultrasonography is essential for intraoperative detection of insulinomas. PMID- 1745988 TI - [The development of anesthesia in german-speaking regions in the 19th century]. AB - Following the first public demonstration of ether anaesthesia by W.T.G. Morton on October 16, 1846, the pioneers to perform ether anaesthesia in German speaking countries were H. A. Demme, surgeon at the University Hospital Bern, Switzerland, on January 23, 1847, the German surgeon J. F. Heyfelder at Erlangen on January 24, and the Austrian surgeon F. Schuh in Vienna on January 27, 1847. The first books in German language referring to clinical experience with and experimental research on sulphuric ether were published in March/April 1847. After the introduction of chloroform the use of ether anaesthesia rapidly decreased. Chloroform administration was smoother and much more easier not requiring any special apparatus. Chloroform remained the preferred anaesthetic till the end of the century although there happened significantly more deaths due to this agent than to ether. Since 1863 nitrous oxide again was propagated for pain relief in dental practice. German investigators provided pioneering contributions to the development of local and regional anaesthesia. C. Koller, Vienna, was the first to operate on a patient in local anaesthesia with cocaine. The next steps were the introduction of infiltration anaesthesia by C. L. Schleich in 1892/1894 and of spinal anaesthesia by A. Bier in 1899. The ultimate success of local and regional anaesthesia was made possible by using adrenaline with the local anaesthetic (1901) and by the introduction of novocaine in 1905.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745989 TI - [Cardiac risk patients in anesthesia]. AB - Cardiac complications are the major cause of morbidity and mortality in patients undergoing noncardiac operations. The perioperative risk of adverse cardiac events is particularly high in patients with significant coronary artery disease, heart failure or critical aortic stenosis. Prolonged intraperitoneal and intrathoracic operations, major vascular surgery, emergency procedures, and intraoperative hypotension and tachycardia promote and increase incidence and severity of cardiac complications. Recent experience has shown, however, that elective noncardiac operations can be performed with justifiable risk even in patients with endstage cardiac disease awaiting heart transplantation. Surgery, if indicated, can thus nowadays hardly be denied even in the presence of high cardiac risk. Successful anesthetic management requires detailed information about the cause and severity of the underlying disease, thorough understanding of its specific hemodynamic particularities, indepth knowledge about hemodynamic effects and interactions of anesthetic drugs, and experience with extended hemodynamic monitoring. Anesthetic choice by itself appears to be of minor significance. Cardiac surgery prior to major elective noncardiac procedures is advocated in patients with significant coronary artery disease or severe valve lesions. The incidence of life-threatening cardiac complications is particularly high in the postoperative period; prolonged hemodynamic monitoring in an intensive care unit is therefore mandatory. PMID- 1745990 TI - [Preparation of children for anesthesia]. AB - Children are not born as little adults, and more important than the difference in size are psychic, physiological and pharmacological aspects. Intense preparatory information and training will be necessary to avoid or reduce psychic trauma due to hospitalization, narcosis and operation. Basic laboratory findings as hemoglobin, hematocrit, urinalysis and blood-group are supplemented by special examinations if indicated. Preoperative fasting shouldn't be prolonged respecting poor metabolic and fluid reserves. Adequate oral or rectal premedication is as important as careful induction. PMID- 1745991 TI - [Anesthesia for ambulatory procedures]. AB - Ambulatory surgery and anesthesia continued to grow and develop over the last few years: Longer lasting and more complex diagnostic and therapeutic procedures are being performed on an outpatient basis. In addition, outpatient procedures, being less disruptive to the patient's everyday life, are of potential benefit especially for children and elderly patients. The proper selection and evaluation of these patients from the anesthesiological and surgical points of view are very important with regard to successful ambulatory interventions. The preoperative assessment is obviously essential. Good communication and teamwork between anesthesiologists, surgeons and admitting doctors are necessary. Patients should be informed early, i.e. before the day of operation, about the planned procedures (fasting periods, adult person necessary to accompany the patient home, etc.), and their written consent should be there. During the preoperative personal interview, the anesthesiologist identifies risk factors which may influence the management and outcome of the anesthetic procedure. Outpatients profit from a short-acting anxiolytic and sedative premedication before entering the operation room. The choice of the anesthetic procedure itself is made individually. An adequate intra- and postoperative monitoring is essential. A checklist with exact discharge criteria is helpful in practice. PMID- 1745992 TI - [Goals and methods of patient monitoring]. AB - Monitoring during and after anaesthesia is aimed at recording changes in physiological functions including the patient's response to the anaesthetic and surgery, and identifying avoidable critical incidents caused by human error or equipment failure. Assessment and control of the depth of anaesthesia would be desirable but cannot yet be accomplished in clinical practice. For every anaesthetic, some degree of primary, basic or minimal monitoring is essential and is, in a number of countries, prescribed or recommended by regulations or guidelines. Besides an alert anaesthetist constantly observing the patient and monitoring the function of the anaesthesia machine, these minimal standards include an ECG, noninvasive blood pressure measurement, pulse oximetry, and end tidal CO2 recording (capnography). ECG, blood pressure, and pulse oximetry also have to be employed during regional anaesthesia and in the post-anaesthesia care unit. The question as to whether further monitoring techniques need to be added (extended or secondary monitoring) will depend upon the medical problems of the individual patient and on the nature and duration of the surgical and anaesthetic procedures. For this purpose, invasive methods are preferentially used, in particular central venous and arterial pressure recording, and a pulmonary artery catheter for measuring pulmonary artery and pulmonary capillary wedge pressures and cardiac output, all in combination with blood gas analysis. PMID- 1745993 TI - [Regional or general anesthesia in patients with pulmonary risks?]. AB - Such partial functions of the respiratory system as ventilation, gas exchange, bronchomotor tone, respiratory regulation, secretion within the airways, mucociliary clearance, etc., are less impaired by such procedures as peridural or spinal anaesthesia than by general anaesthesia. As a result, it is often concluded that regional anaesthesia should always be used preferentially in the case of patients with a pulmonary risk. However, comparative studies have shown that pulmonary morbidity and mortality are little influenced by the anesthetic procedure. For, in the first instance, the incidence of post-operative complications affecting respiration are determined by previous lung pathologies, the age of the patient, and the location and duration of the surgical procedure. These are factors that cannot readily be influenced by anaesthesiological measures. For this reason, the pre-operative diagnostic evaluation and preparation, post-operative prophylaxis and treatment, including the components pain elimination, physiotherapy, respiratory therapy, broncholysis and secretolysis, are more important than the anaesthetic procedure itself. PMID- 1745994 TI - [Role of the anesthetist in the recovery stage]. AB - Surveillance of the patient in the particularly critical phase immediately following operation and anaesthetic must be considered a purely anaesthesiological task. Today, it is no longer considered sufficient merely to keep the patient under observation until his protective reflexes have returnded; rather, appropriate postoperative therapeutic measures must be initiated already during the recovery phase to enable the patient to be returned to the nursing ward with his or her vital functions optimal and stabilised. The tasks of the anaesthetist in the recovery phase are as follows: safeguarding of the transportation phase of the patient from the operating room to the recovery unit; hand-over of the patient to the recovery staff; monitoring for possible complications in the recovery phase, collection of suitable diagnostic parameters to determine the current state of the patient; initiation of optimised treatment as dictated by the state of the patient; documentation of all findings as well as all therapeutic measures instituted, and deciding on the further transfer of the patient. PMID- 1745995 TI - [Case of the month: severely injured motorcycle rider]. PMID- 1745996 TI - The effect of flow on hemostasis and thrombosis. AB - While dilution of procoagulants has generally been proposed as the mechanism by which flow reduces coagulation at surfaces, such a mechanism has never been verified experimentally and, in fact, there are theoretical grounds for suspecting the validity of such a hypothesis (29). It is quite plausible that flow may have direct effects on certain enzyme or polymerization kinetics involved in thrombosis, in addition to the well-defined effect that flow has an enhancing transport of reactants and products to and from the vessel wall. Such effects of flow on immobilized enzymes have occasionally been observed, but never studied with respect to coagulative processes (30). The study of the effects of flow on hemostasis and thrombosis, while numerous, are still in their infancy. As noted above, increasing shear increases the rate of formation of factor Xa in a tubular reactor. In the presence of factors VIII and IX, there is also a shear induced enhancement of Xa production (31). These studies indicate that at least some coagulation reactions are accelerated in the presence of high shear. However, it has been observed that fibrin formation is diminished at increasing shear rates (20). This implies that at least one step of the coagulation cascade is being inhibited by high shear. One possibility is that fibrin monomer is being removed by the high local flow conditions, although the concomitant reduction in fibrinopeptide A argues against this interpretation. Another possibility, not yet tested, is that thrombin itself is removed by flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745997 TI - Dose finding study of a low molecular weight heparin, Innohep, in haemodialysis. AB - A pilot investigation was performed with Innohep, a low molecular weight (LMWH) preparation (peak maximum molecular mass 3,000-6,000), to determine possible dose regimens for patients undergoing regular maintenance haemodialysis for chronic renal failure. Results from this study suggested that suppression of macroscopic clot formation and fibrinopeptide A (FPA), a marker of fibrin formation, could be achieved following bolus injections rather than bolus injections and an infusion. On the basis of these preliminary findings, a randomised crossover study was performed in eight patients undergoing regular maintenance haemodialysis for 5-7 h to determine the effective antithrombotic dose of this LMWH. Single i.v. bolus doses of 1,250 AFXa u, 2,500 AFXa u and 5,000 AFXa u (n = 7-8) were compared to an UFH regime of 5,000 iu + 1,500 iu/h. Excessive clot formation in the dialyser bubble trap, necessitating additional UFH to enable completion of a prolonged (up to 7 h) dialysis, was observed in all patients on the 1,250 AFXa u dose (mean duration of dialysis prior to UFH, 3 h) but in a single patient only receiving the other LMWH doses. A dose-related response in the AFXa activity, measured by chromogenic substrate (CS) assay was seen in the three LMWH groups, with levels declining significantly (p less than 0.05) from 1-7 h. This contrasted with the constant levels maintained during dialysis with UFH. FPA levels were significantly elevated after 2 h following the 1,250 AFXa u bolus and after 4 h following the 2,500 AFXa u bolus. There was no significant difference in FPA levels between the 5,000 AFXa u bolus and UFH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745998 TI - Extrinsic activation of human coagulation factors IX and X on the endothelial surface. AB - In previous kinetic studies, the catalytic efficiency of the activation of human coagulation factors IX and X by factor VIIa in the presence of purified tissue factor apoprotein was found to be essentially equal. These activation reactions were now studied on the surface of human umbilical vein endothelial cells. The cells were stimulated with endotoxin to express tissue factor. This tissue factor activity was saturable with factor VIIa and could be inhibited by rabbit antibodies against human tissue factor apoprotein. Only stimulated cells supported factor VIIa activity. No difference in the reactivity of factor VII and VIIa was observed in the presence of factor X, due to rapid feedback activation of factor VII by factor Xa. However, the activation of factor IX by factor VII shows a 10 min lag-phase, which reflects that the activation of factor VII by factor IXa is a less efficient process. The kinetic parameters for the factor VIIa dependent activation of factor IX and factor X on the endothelial surface were: Km 0.09 microM, Vmax 0.13 pmol/min, and Km 0.071 microM, Vmax 0.41 pmol/min, respectively. The same ratio between the Vmax for factor X and factor IX activation was observed as in a cell free system. However, the Km of factor IX was 4-fold higher on the endothelial surface than in the cell free system. Together, these kinetic parameters will favour factor X activation 5-fold over factor IX activation at physiological concentrations of these proteins. The activation of factor X by factor VIIa on the endothelial surface was characterized by a short lag-phase, which was absent in factor IX activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1745999 TI - Coagulation and fibrinolytic activity in Behcet's disease. AB - Coagulation and fibrinolytic activities were studied in 18 subjects with Behcet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behcet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/l, p less than 0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p less than 0.002; plasminogen activator activity (10(6)/ECLT2) 219 (94-329) vs 137 (78-197) units, p less than 0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p less than 0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p less than 0.002. Protein C antigen was significiantly lower: 97 (70-183) vs 126 (96-220)%, p less than 0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and B beta 15-42, plasminogen, alpha-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behcet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behcet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behcet's disease was detected. PMID- 1746000 TI - Effect of the hirudin carboxy-terminal peptide 54-65 on the interaction of thrombin with platelets. AB - The carboxy-terminal region of hirudin (residues 54-65) has previously been shown to inhibit thrombin clotting activity without binding to the catalytic site of the enzyme. In the present study, the effect of hirudin 54-65 on thrombin interaction with specified platelet proteins has been investigated. Hirudin 54-65 was found to inhibit thrombin-induced platelet aggregation and secretion in a dose-dependent manner. Substitution of either Phe56, Glu57, Ile59, Pro60 or Leu64 showed that these residues were critical for inhibition of thrombin-induced platelet activation whereas sulfation of Tyr63 increased the inhibitory potency of the peptide. Hydrolysis of glycoprotein V, a platelet membrane substrate for thrombin, was only partially inhibited by hirudin 54-65. Although hirudin 54-65 did not decrease the amount of thrombin bound to platelets during cross-linking experiments, it was found to inhibit the specific binding of thrombin to platelet glycoprotein Ib. Since the carboxy-terminal region of hirudin has previously been reported to bind near the trypsin-catalyzed beta cleavage site, we have analyzed the consequences of alpha to beta-thrombin conversion on both thrombin-hirudin 54 65 interaction and thrombin activity toward platelets. The beta cleavage induced a decrease in the affinity of thrombin for both glycoprotein Ib and hirudin 54 65. Altogether, our results indicate that thrombin recognition sites for hirudin 54-65 and platelet membrane glycoprotein Ib share common structures located near the beta cleavage site at Arg 73 on the thrombin B chain. PMID- 1746001 TI - Factor IX a inhibition contributes to the heparin effect. AB - We investigated whether the inactivation of factor IXa contributes to the partial inhibition of thrombin formation that is observed at therapeutic concentrations of heparin. The action of standard unfractionated heparin (0.05 U/ml) on thrombin formation in the intrinsic system was compared to that of a mixture of dermatan sulfate (DS) and a synthetic pentasaccharide (PS). DS enhances the action of heparin cofactor II which inhibits thrombin only. PS specifically enhances the anti-factor Xa activity of antithrombin III (AT III). The concentrations of DS and PS were chosen so as to obtain equal anti-thrombin and anti-factor Xa activities as in 0.05 U/ml heparin. An extra inhibitory effect of heparin over the mixture is observed in situations where free factor IXa, not bound to factor VIIIa and phospholipid, limits the rate of thrombin formation, notably in contact activated plasma. We conclude that the inactivation of free factor IXa by heparin contributes importantly to the inhibition of thrombin formation in the intrinsic system such as e.g. measured in the activated partial thromboplastin time. PMID- 1746002 TI - Molecular cloning, characterization and expression of cDNA for rabbit brain tissue factor. AB - Tissue factor (TF) is a membrane anchored glycoprotein that initiates blood coagulation by forming a complex with circulating factor VII or VIIa. TF has been identified in atherosclerotic plaques and may possibly trigger thrombosis after spontaneous plaque rupture as seen in acute myocardial infarction or angioplasty. We have previously developed an atherosclerotic rabbit model for study of the acute and chronic outcomes following angioplasty. As a first step in developing inhibitors of TF, we have isolated and characterized a rabbit cDNA coding for the mature TF. The sequence comparison of rabbit TF cDNA with those of human and mouse TFs show considerable similarity at both the nucleotide and amino acid levels. The TF cDNA when expressed in E. coli demonstrates a procoagulant activity comparable to that of native rabbit brain TF. The TF activity can be blocked by a polyclonal antibody against rabbit TF. PMID- 1746003 TI - A kinetic model of the circulatory regulation of tissue plasminogen activator. AB - A computer simulation was developed to study the regulation of active tissue plasminogen activator (t-PA) levels in plasma by kinetically modeling t-PA secretion, t-PA inhibition by plasminogen activator inhibitor type 1 (PAI-1), and hepatic clearance of t-PA, PAI-1 and t-PA/PAI-1 complex throughout a simplified human circulatory system. The model indicates that as the active PAI-1 concentration increases, the percent of t-PA in the active form decreases exponentially. Further, the reaction between t-PA and PAI-1 substantially reduces the half-lives of both active factors. By adjusting the t-PA and PAI-1 secretion rates to provide the best fit between simulated and measured circadian variations in t-PA, PAI-1 and complex, the model predicts that the diurnal rhythm in active t-PA levels is principally due to changes in the rate of PAI-1 secretion and not to variations in the t-PA secretion rate. In conclusion, the model predicts that PAI-1 is an important regulator of the concentration, half-life and circadian variation of active t-PA. PMID- 1746004 TI - 125I-fibrinogen binding to platelets in myeloproliferative disease. AB - Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain. PMID- 1746005 TI - Rapid aequorin loading into platelets in the presence of DMSO--characteristics of the responses (changes in light transmission and in calcium) to various agonists. AB - We have looked at different parameters which could modify platelet behaviour during and after aequorin loading in the presence of DMSO. There is a decreased platelet reactivity in response to ADP, PAF and A-23,187 which appears to be mainly due to the exposure to EGTA during washing and loading and the 1 ml volume of the test suspension. All the studied agonists (including PMA) which elicit aggregation are able to induce an intracellular Ca2+ change detected with the aequorin probe. By contrast, epinephrine alone induces neither aggregation nor Ca2+ rise, but potentiates the responses to ADP. Different consecutive phases in Ca2+ changes after stimulation with ADP, PMA and A-23,187 can be evidenced. In the presence of external Ca2+, the second component of the Ca2+ change evoked with ADP is dependent on aggregation and the subsequent TXA2 synthesis. When the external medium is Ca2+ depleted, the two Ca2+ peaks induced by ADP disappear whereas a Ca2+ rise persists (endogenous mobilization) with the other agonists, being independent of TXA2 and ADP release. Ca2+ mobilization parallels activation with A-23,187 but not with low concentrations of thrombin. PMID- 1746006 TI - Dipyridamole potentiates platelet inhibition by nitric oxide. AB - In a placebo-controlled double blind cross-over experiment the adenosine uptake inhibitor dipyridamole (400 mg/day) did not affect ex vivo platelet aggregation induced by collagen or adenosine-diphosphate (ADP) in an electronic whole blood aggregometer (WBA). Dipyridamole was also inactive in vitro, unless red blood cell injury was deliberately enhanced, thereby increasing the level of free adenine nucleotides. Since dipyridamole also inhibits cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE), we used platelet rich plasma (PRP) to study its interaction with authentic and endothelium-derived nitric oxide (NO). The latter inhibits platelets by increasing cyclic GMP. Dipyridamole (1 to 30 microM), either alone or in combination with a subthreshold concentration of prostacyclin (PGI2), was inactive. However, when combined with a subthreshold concentration of NO, dipyridamole caused a concentration-dependent platelet suppression, which became more pronounced when PGI2 was present as well. It is concluded that dipyridamole could reduce the threshold for platelet suppression by NO through inhibition of cyclic GMP PDE. PMID- 1746007 TI - Loss of thrombin-induced Ca2+ mobilization in a subpopulation of platelets during storage. AB - Thrombin-induced changes in cytosolic free Ca2+ ([Ca2+]i) were studied in human platelets that had been stored for up to 6 days. Changes in [Ca2+]i were measured with Indo-1-loaded platelets and quantitated with two different methods: (i) measurement of the changes in total fluorescence; (ii) measurement of the [Ca2+]i changes in individual platelets in a flow cytometer, allowing the detection of non-responding platelets. The maximal concentration of [Ca2+]i after stimulation with 0.5 U of thrombin/ml decreased from 544 +/- 58 nM (mean +/- SEM, n = 6) on day 0, to 276 +/- 9 nM on day 3 and to 203 +/- 23 nM on day 6. The percentage of platelets responding to 0.5 U of thrombin/ml declined from 90 +/- 2% on day 0 to 72 +/- 4% on day 3, and to 47 +/- 8% on day 6. Nevertheless, also the responding platelets showed a decreased rise in [Ca2+]i. The study shows that during platelet storage a decrease in the rise in [Ca2+]i upon thrombin stimulation occurs. This decrease is partly due to the formation of a subpopulation of platelets that is completely unresponsive and partly due to a decreased responsiveness in the remainder of the platelets; it is not due to a gradual decline in [Ca2+]i rise in all platelets. This phenomenon provides new insight in the functional defect of stored platelets. PMID- 1746008 TI - LY53857, a 5HT2 receptor antagonist, delays occlusion and inhibits platelet aggregation in a rabbit model of carotid artery occlusion. AB - The present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 microM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 microM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 +/- 16.7% inhibition), collagen (76.1 +/- 15.9% inhibition) and U46619 (65.2 +/- 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 +/- 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 micrograms/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 micrograms/kg i.v. occlusion time extended to 164 +/- 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 micrograms/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 microM) and serotonin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746009 TI - Characterization of epitheloid cells from human omentum: comparison with endothelial cells from umbilical veins. AB - Capillary cells represent 95% of the vascular bed, and cells from large and micro vessels do not express identical functions. In order to study the hormonal regulation of plasminogen activator inhibitor 1 (PAI-1) secretion by human capillary cells we used epithelial cells from omental tissue (HOTMEC). As their endothelial origin is subject to controversy, we attempted to determine their characteristics by comparing them to human umbilical vein endothelial cells (HUVEC). Morphological and biological criteria were studied. By phase contrast microscopy HOTMEC elicited a cobblestone pattern similar to HUVEC. Weibel-Palade bodies were not found in the cytoplasm with electron microscopy. Fluorescence microscopy studies indicated that HOTMEC took up acetylated-LDL more intensely than HUVEC, and showed no staining for von Willebrand factor. The phenotype of HOTMEC was studied by flow cytometry using monoclonal antibodies (mo Ab) directed against epitopes either specific for endothelial cells or for mesothelial cells. We showed that in our preparations only 10% of cells reacted with mo Ab specific for endothelial cells. About 60% of the HOTMEC were labelled with an antibody directed against mesothelial cells. HOTMEC expressed fibrinolytic factors. Tissue plasminogen activator (t-PA) levels in HOTMEC conditioned medium were 50 fold higher than those of HUVEC, and the PAI-1 secretions were identical in both cell types. Insulin which is known to increase PAI-1 synthesis by hepatocytes did not enhance the PAI-1 level either in HOTMEC or in HUVEC conditioned media. Our results suggested that morphological and functional methods did not allow discrimination between the cell types present in the omentum tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746010 TI - Registry of multicenter clinical trials. Eleventh report--1989. PMID- 1746011 TI - The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. PMID- 1746012 TI - An artefact related to the ratio of sample volume to the blood collection vial size which effects the APTTs of specimens taken to monitor heparin therapy. PMID- 1746013 TI - The effect of lupus anticoagulant (LA) on clotting assay for plasma protein C (PC) PMID- 1746014 TI - Experience of surgical treatment for craniofrontonasal dysplasia. AB - We present a case of a 5-year-old girl diagnosed as having craniofrontonasal dysplasia (CFND), which was first reported by Cohen in 1979. CFND is very rare and reports concerning this syndrome have never been found in Japan. In our case, frontal plagiocephaly, third degree orbital hypertelorism and clefting nasal tip coexisted. At 10 months after birth when she visited our hospital, signs of craniostenosis were not recognized and cosmetic improvement was considered the main purpose of the treatment. We performed supraorbital bar reshaping, ethmoidectomy and orbitotomy for reconstruction in one-stage at the age of five. The operation produced marked improvement in her exotropia before entering a primary school. Past reports dealing with abnormalities of the central nervous system in this syndrome are few, but agenesis of the splenium was noted in our case. This paper is a report of our findings together with some discussions in reference to the literature. PMID- 1746015 TI - Serum level of interferon-gamma in autoimmune diseases. AB - Interferon-gamma is one of the cytokines which have various immunoregulatory functions. In the present study, the serum interferon-gamma level was determined in autoimmune diseases. It was increased in the active cases of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Since there was a positive correlation between the serum interferon-gamma level and the rate of peripheral mononuclear cells positive for HLA-DR antigen in systemic lupus erythematosus, circulating interferon-gamma might have a biological functions as suggested by many in vitro studies. In rheumatoid arthritis and Sjogren's syndrome, there was no correlation between the serum interferon-gamma level and the clinical findings. These data suggest that interferon-gamma might be associated with the pathogenesis of autoimmune diseases such as SLE and MCTD, and it can be one of the indices for their disease activity. PMID- 1746016 TI - Cost-effectiveness analysis of screening for colorectal cancer in Japan. AB - To clarify the best cost-effective screening strategy for colorectal cancer in Japan, the cost-effectiveness ratio was compared among six currently performed procedures. The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. In the screening by the immunological fecal occult blood test (FOBT), a comparison between the one- and two-day fecal collection methods indicated that the latter was more cost effective than the former. A comparison was also made on the four workup methods: barium enema (BE) alone, a combination of BE and sigmoidoscopy (BE + SIG), total colonoscopy (TCF) alone, and a combination of BE and TCF (BE + TCF). The cost effectiveness ratio was the lowest in the method using TCF alone, followed by those based on BE alone and BE + TCF, and the highest in the BE + SIG method. The superiority of TCF alone strategy was stable over a range of estimates such as the sensitivity of diagnostic tests, the probability of complications due to TCF, etc. It is concluded that a combination of the two-day FOBT and TCF yields the best cost-effectiveness. PMID- 1746017 TI - Cost-effectiveness analysis of screening for gastric cancer in Japan. AB - Cost-effectiveness analysis of gastric cancer screening in Japan was performed, and the cost-effectiveness ratio was compared with that of colorectal cancer screening. The analytical model was the same as that adopted in our previous study on colorectal cancer screening (Tsuji et al. 1991). The results indicated that the cost per case-fatality prevented by colorectal cancer screening was 5.5 and 2.7 times more expensive for males and females, respectively, than that by gastric cancer screening. The age of the population influenced the cost effectiveness of screening programs. The cost-effectiveness ratio in gastric cancer screening became negative among males older than the age of 65 years, suggesting that the total cost for prevention and control of deaths by gastric cancer in these age populations is saved by the screening program. PMID- 1746018 TI - Effect of S-8666 on Cl- transport in the rabbit connecting tubule perfused in vitro. AB - S-8666, [6, 7-dichloro-5-(N, N-dimethylsulfamoyl)-2, 3 dihydrobenzofurancarboxylic acid] is a potent diuretic with uricosuric action. Although the major site of action of S-8666 has been proven by the in vitro microperfusion study to be the thick ascending limb of Henle's loop, clearance studies in the rat suggested that this drug has an additional thiazide-like action. To provide direct evidence that S-8666 acts also on distal nephron segments, we examined effect of S-8666 on Cl- flux across the rabbit connecting tubule perfused in vitro. The drug suppressed the lumen-to-bath Cl- flux by 96 +/ 41 (S.E.)pmol.mm-1.min-1 (n = 9) without affecting transmural voltage. To demonstrate that S-8666 acts on the connecting tubule cell, the target of thiazide diuretics, we compared effects of S-8666 and trichlormethiazide on the basolateral membrane voltage of the connecting tubule cell. Both drugs added to the lumen caused a small but significant hyperpolarization of the basolateral membrane without affecting transmural voltage. We conclude that S-8666 is a unique uricosuric diuretic having actions on both thick ascending limb of Henle's loop and connecting tubule. PMID- 1746019 TI - A continuously rotating passive agglutination method using rapidly precipitable latex particles and its application. AB - A new passive agglutination method is reported. Large, very heavy, uniform latex particles coated with antigens or antibodies were mixed with corresponding antibodies or antigens in reacting wells of an appropriate shape and size. Agglutination results were read after 30 min of continuous rotation at a suitable speed. With this simple and rapid continuously rotating passive agglutination method, we could detect anti-dinitrophenol monoclonal antibodies, natural anti dinitrophenol antibodies, rheumatoid factor, allergic antibody to tick, human chorionic gonadotrophin and human IgE. This method is suitable to detect weak and small quantities of antibodies in a brief time. PMID- 1746020 TI - Association between cadmium-induced renal dysfunction and mortality: further evidence. AB - Our previous follow-up study, carried out from 1979 to 1989, on 256 residents of Sasu, a cadmium (Cd)-polluted area located on Tsushima Island, Nagasaki Prefecture, Japan, showed a significant relationship between urinary beta 2 microglobulin (beta 2-m) excretion and mortality in men. To investigate the association between Cd-induced renal dysfunction and mortality more precisely, 275 residents in the same area aged 40-92 years, who had participated in a health survey conducted in May 1982, were followed to February 1989. The expected number of deaths was calculated on the basis of the sex- and 5-year-age-specific mortality rates for Tsushima Island in 1985. In both men and women with urinary beta 2-m concentrations greater than 1,000 micrograms/g creatinine, observed deaths were greater than the expected. However, the P value of the difference was less than 0.05 only in women. Analysis by the Cox proportional hazards model showed that, in both men and women, serum beta 2-m and creatinine, as well as urinary total protein and beta 2-m were significantly or marginally significantly related to mortality independent of age. In men, serum beta 2-m was more strongly related to mortality than urinary beta 2-m. The results provide further evidence for the causal association between Cd-induced renal dysfunction and mortality. The present report also discusses the role played by decreased glomerular filtration rate in the excess mortality of subjects with Cd-induced renal dysfunction. PMID- 1746021 TI - Electroencephalographic patterns related to hemodynamic changes at the onset of cardio-pulmonary bypass circulation. AB - Electroencephalographic (EEG) changes in relation to hemodynamic changes at the onset of cardio-pulmonary (C-P) bypass circulation in 31 cases undergoing open heart surgeries were studied. Rapid and extensive changes in systemic circulation, which were followed by abnormal EEGs, appeared within the first five minutes of C-P bypass. Abnormal EEG patterns including disappearance of fast waves, slowing under 6 Hz in frequency with high voltage and flattening were observed in 64% of the cases. The relations between the appearance of these abnormal EEGs and hemodynamic factors such as mean arterial pressure (mAP), central venous pressure (CVP), rate of decrease in mAP and rate of change in CVP, were analyzed in order to elucidate causes of development of the abnormal EEGs. Only the rate of decrease in mAP at the onset of C-P bypass had a high correlation (p less than 0.01) with the appearance of abnormal EEGs. The findings suggest that rapid circulatory changes in the first five minutes of C-P bypass may induce disruption of cerebral autoregulation. PMID- 1746022 TI - Thiobenzamide-induced hepatotoxicity: effects of substituents and route of administration on the nature and extent of liver injury. AB - Differences in the nature and extent of hepatic injury were examined after administration of para-substituted thiobenzamides to rats. In accordance with previous studies, the extent of hepatotoxicity varied with the electron-donating ability of the substituent. There was also a good correlation between the extent of hepatic necrosis and the amount of substituted thiobenzamide sulfoxide found in the plasma after intraperitoneal dosing. The nature of the hepatic lesion, characterized as a combination of hepatic necrosis, ballooning degeneration, and biliary dysfunction, varied qualitatively with each thiobenzamide analog. When the hepatotoxicity of thiobenzamide was compared after either intraperitoneal or oral dosing, differences in the extent of hepatic necrosis, ballooning degeneration, transaminase elevation, and biliary dysfunction were observed. Intraperitoneal dosing with thiobenzamide gave less severe necrosis and more pronounced elevations in bile acids, while oral dosing led to more severe necrosis along with impaired biliary function. The route of administration was shown to dramatically affect the pharmacokinetics of thiobenzamide and thiobenzamide sulfoxide. Intraperitoneal administration of thiobenzamide gave high plasma and liver levels of both thiobenzamide and thiobenzamide sulfoxide, whereas oral administration gave slightly lower levels of the sulfoxide but much lower levels of thiobenzamide. The reason for greater hepatic necrosis after oral administration may be due to a greater ability to further metabolize the sulfoxide to a reactive metabolite in the absence of high levels of thiobenzamide. PMID- 1746023 TI - Regional increases in rat nasal epithelial cell proliferation following acute and subchronic inhalation of formaldehyde. AB - Short-term studies (9 days) in the rat have demonstrated that formaldehyde induced nasal epithelial lesions are associated with increases in surface epithelial cell proliferation rates. The present studies were designed, in part, to investigate cell proliferation rates in the nasal epithelium of rats exposed to formaldehyde for a longer duration in order to determine if correlations exist between (1) the concentration-response in cell proliferation rate with the previously published formaldehyde bioassay tumor response; (2) sites of increased cell proliferation and the regions of the nasal passages that exhibit formaldehyde-induced cytotoxicity; and (3) sites of increased cell proliferation and the regions of the rat nasal passages previously determined to be most susceptible to neoplasia (i.e., the lateral meatus and nasal septum of the anterior nasal passages). Another important endpoint of this study was to provide data for a comparison of formaldehyde-induced responses in rats with previous findings in rhesus monkeys. Fischer-344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 6 weeks and pulse labeled with tritiated thymidine prior to each scheduled termination. Exposure to formaldehyde at 6 ppm or higher induced site-specific lesions in the nasal respiratory epithelium and was associated with increases in cell proliferation rate which remained statistically elevated throughout the 6 weeks. While a direct correlation between sites susceptible to formaldehyde-induced nasal cancer and increased cell proliferation was not evident, results from the present studies did demonstrate a clear correlation between sites of cellular injury and increases in cell proliferation and a concentration-dependent response which correlated with the previously published formaldehyde bioassay tumor response. Furthermore, this work demonstrated that formaldehyde-induced responses in rats exposed to 6 ppm were morphologically similar to those reported in the rhesus monkey; however, the distribution of lesions between the two species differed significantly. PMID- 1746024 TI - 2,5-Hexanedione exposure alters the rat Sertoli cell cytoskeleton. I. Microtubules and seminiferous tubule fluid secretion. AB - 2,5-Hexanedione (2,5-HD) is a testicular and nervous system toxicant with an unknown mechanism of action. In this study, the effects of 2,5-HD on seminiferous tubule fluid (STF) secretion, testis morphology, and tubulin distribution were examined. Charles River CD rats (200 g) were exposed to 1% 2,5-HD in the drinking water for 5 weeks followed by a 3-week recovery period. STF secretion was measured by efferent duct ligation, and testis cross sections were prepared at 2, 3, 3.43, 3.57, 3.86, 4, and 8 weeks after beginning exposure. A dramatic inhibition of STF secretion was observed between Weeks 3 and 4. The inhibition of STF secretion occurred following simultaneous changes in Sertoli cell and elongate spermatid morphology but prior to changes in round spermatid morphology. Also, alterations in seminiferous tubule tubulin distribution were observed with kinetics similar to those for changes in seminiferous tubule morphology. This temporal sequence suggests a model of 2,5-HD-induced injury in which populations of germ cells are differentially sensitive to impairment of Sertoli cell function. PMID- 1746025 TI - 2,5-Hexanedione exposure alters the rat Sertoli cell cytoskeleton. II. Intermediate filaments and actin. AB - The effects of 2,5-hexanedione (2,5-HD) exposure on the expression of intermediate filament and actin proteins in adult rat testis was examined during progressive stages of testicular injury. The distribution of vimentin within testis cross sections was examined using immunohistochemistry while rhodamine labeled phalloidin was used to localize filamentous actin. Keratin was not detected in immunoblots of intermediate filament proteins tested with an antikeratin antibody to investigate the possible reexpression of the prepubertal intermediate filament protein keratin in 2,5-HD-exposed adult testes. However, 2,5-HD exposure did result in a progressively abnormal distribution of actin and vimentin within the seminiferous epithelium with the appearance of a high molecular-weight protein which was vimentin immunoreactive and not present in control testes. PMID- 1746026 TI - Cadmium accumulation and metallothionein concentrations after 4-week dietary exposure to cadmium chloride or cadmium-metallothionein in rats. AB - The distribution of cadmium was examined in rats fed diets containing either cadmium-metallothionein (CdMt) or cadmium chloride (CdCl2) for 4 weeks. The test diets contained 3, 10, or 30 mg Cd/kg diet (3, 10, or 30 ppm) as CdMt or 30 mg Cd/kg diet (30 ppm) as CdCl2. A second study was performed to establish the Cd content in liver and kidneys after exposure to low doses of both CdMt and CdCl2 (1.5 and 8 ppm Cd). The feeding of CdMt resulted in a dose- and time-dependent increase of the Cd concentration in liver, kidneys, and intestinal mucosa. Rats fed 30 ppm CdMt consistently showed less Cd accumulation in liver and intestinal mucosa than did rats fed 30 ppm CdCl2. However, renal accumulation in rats fed 30 ppm was similar until Day 28 regardless of Cd form. At lower dietary Cd levels (1.5 and 8 ppm), relatively more Cd is deposited in the kidneys, although even at these doses the kidney/liver ratio of Cd is still higher with CdMt than with CdCl2. Tissue metallothionein (Mt) levels in the intestinal mucosa were relatively constant but always higher after CdCl2 exposure than after CdMt exposure. Mt levels in both liver and kidney increased after CdCl2 or CdMt exposure during the course of study. Although Mt levels in liver were higher after CdCl2 intake (30 ppm) than after CdMt intake (30 ppm), renal Mt concentrations were the same for both groups. In fact on Day 7, CdMt administration resulted in slightly higher Mt levels than CdCl2 administration, suggesting a direct accumulation of exogenous CdMt in the kidneys. In conclusion, after oral exposure to CdMt in the diet there is a relatively higher Cd accumulation in the kidneys. However, the indirect renal accumulation via redistribution of Cd from the liver might be lower than after CdCl2 exposure. Which of these two phenomena is decisive in the eventual level of renal toxicity of Cd after long-term oral intake could determine the toxicological risk of the chronic intake of biologically incorporated Cd. PMID- 1746027 TI - Effects of cigarette smoke on the immune response. II. Chronic exposure to cigarette smoke inhibits surface immunoglobulin-mediated responses in B cells. AB - We have previously reported that chronic exposure of rats to cigarette smoke inhibits the antibody-forming cell (AFC) response to both T-dependent and T independent antigens and may reflect B cell dysfunction. In this communication we extend these studies to show that T cell functions are normal in chronically smoke-exposed rats (SM) as judged by their responses to mitogens and "nominal" or alloantigens. While B cells from SM respond significantly to the B cell mitogen lipopolysaccharide (LPS), they fail to proliferate in response to anti-IgM (anti mu) or to produce significant AFC response to sheep red blood cells. On the basis of the number of rosettes formed with trinitrophenylated (TNP) horse red blood cells; the frequency of TNP-binding cells (TNP-ABC) in the spleens of SM is comparable to sham control rats. However, the proliferation of TNP-ABC to TNP Brucella abortus is significantly decreased in SM. These differences in SM B cell responses, i.e., between LPS and anti-mu/antigen, may to be related to the ability of LPS to bypass a portion of the membrane signal transduction cascade. These results suggest that cigarette smoke affects an early step(s) in the antigen-dependent B cell signal transduction pathway. PMID- 1746028 TI - Iatrogenic gangrene in the Third World. PMID- 1746029 TI - Xerophthalmia in malnourished Sudanese children. AB - Two hundred and thirteen Sudanese children (4-60 months old) with malnutrition were examined for signs of xerophthalmia. Sixty-three (29%) of these children were found to have varying stages of xerophthalmia. These included 35 (56%) patients with conjunctival xerosis, 12 (19%) with Bitot's spots, seven (11%) with corneal xerosis, seven (11%) with corneal ulceration and two (3%) with corneal scar. Direct questioning of the parents of these children revealed evidence of night blindness in nine (4%) of all patients. All nine patients had signs of xerophthalmia which showed good response to vitamin A therapy. PMID- 1746030 TI - An experience in the control of plague in Botswana. AB - In October 1989, cases of human plague started to occur in Boteti district of Botswana. One hundred and seventy cases were recorded in total from 15 October 1989 to 6 April 1990. There were 12 deaths, giving a case fatality rate of 7%. All cases were of the bubonic type. A concerted control strategy based on sentinel surveillance, involving public education, flea and rodent control, chemotherapy and chemoprophylaxis controlled the epidemic. PMID- 1746031 TI - A hospital study of the complications of female circumcision. AB - During one year 118 patients were admitted to the operative gynecological ward of Banadir Maternity Hospital, Mogadishu, Somalia, with diseases related to the practice of female circumcision. Fifty-five per cent of the patients were suffering from a dermoid cyst at the site of the excised clitoris. Thirty-six per cent had a vaginal stenosis and 9% an abscess at the site of the excised clitoris. These patients occupied the beds of the hospital for a total period of 1967 days which posed a significant constraint to the health services of the hospital. PMID- 1746032 TI - Management of bowel perforation in typhoid fever. AB - The best survival rates after ileal perforation in typhoid fever are to be found in patients undergoing operation within 24 h. Conservative management of typhoid perforation, which was widely advocated after the introduction of chloramphenicol, appears to be associated with a substantially increased mortality compared to surgery, although randomized comparisons have never been conducted. Clinical, radiological and ultrasound examination assist in the diagnosis of perforation. After vigorous resuscitation, simple surgical closure of the perforation and abdominal irrigation will suffice for most cases. Antibiotics effective against S. typhi, coliforms and anaerobes are required. PMID- 1746033 TI - Recurrent haemoptysis? Think of paragonimiasis. PMID- 1746034 TI - Anaesthesia training in Malawi. PMID- 1746035 TI - Appropriate management of femoral neck fractures in Nepal. AB - The management of femoral neck fractures in the Third World has always been a problem. Its management in Nepal reflects the level of available treatments for other orthopaedic conditions, as well as for medical care in general. The most successful methods of fracture treatment have remained the simple ones, consistent with the available resources. Adherence to this philosophy of management, carried out with attention to the needs of the people, reduces the incidence of iatrogenic complications. Six years of experience in the management of femoral neck fractures by traction, plaster, McMurray's osteotomy, modified Girdlestone's excision arthroplasty and Austin Moore prosthetic replacement have been reviewed, along with the relevant literature. Non-operative management has been found to be the most satisfactory method of treatment when related to the overall medical resources in Nepal. PMID- 1746036 TI - How well are hospitals preventing iatrogenic HIV? A study of the appropriateness of blood transfusions in three hospitals in the Ashanti region, Ghana. AB - A study on the appropriateness of blood and blood product transfusions took place in three hospitals over a 3-week period in July/August 1990 in the Ashanti region of Ghana. Clinical records of all blood transfusion recipients within the period were examined for the appropriateness of the transfusions based on preset criteria. Nearly 1 in 5 (17%) of all blood transfusion episodes in the hospitals were avoidable according to these criteria. Surgical practices were associated, perhaps habitually, with many more avoidable blood transfusions than non-surgical medical practices. The need to minimize the use of transfusion therapy is reemphasized since human immunodeficiency virus screening is imperfect. There is the need for hospitals to develop reasonable, practical guidelines for transfusions in all departments. PMID- 1746037 TI - Value of fibreoptic oesophago-gastro-duodenoscopy: experience with 4000 procedures at Kilimanjaro Christian Medical Centre, Moshi, Tanzania. AB - The paper presents the results of a retrospective study and the experiences with 4000 fibreoptic oesophago-gastro-duodenoscopies (EGD), which were performed at Kilimanjaro Christian Medical Centre (KCMC) between 1985 and 1989 in an open access service. Seventy per cent of all patients examined had abnormal findings with duodenal ulcer as the most frequent diagnosis (22%). Pyloric stenosis was seen in 6%, gastric ulcer in 5% and esophageal varices in 4% of all patients. High figures were found for carcinoma of the esophagus (4%) and malignancy of the stomach (5%). Gastritis was diagnosed in 11%. We consider fibreoptic EGD a cost effective and appropriate technology. Because of its high diagnostic yield, we advocate its use in certain centres in developing countries. PMID- 1746038 TI - Bacterial agents in neonatal septicaemia in Calabar, Nigeria: review of 100 cases. AB - This study of bacterial isolates in 100 cases of proven neonatal septicaemia has shown Staphylococcus aureus and coliform bacteria as the dominant Gram-positive and Gram-negative organisms respectively. Most Gram-negative bacteria and Staphylococcus aureus were sensitive to gentamicin, while streptococci were sensitive to ampicillin and penicillin. On the basis of this antimicrobial sensitivity pattern, the combination of gentamicin with either ampicillin or penicillin appears appropriate in initial therapy of neonatal septicaemia. PMID- 1746039 TI - Use of loupe in paediatric bronchoscopy. PMID- 1746040 TI - High dose oral diazepam and early full alimentation in neonatal tetanus. PMID- 1746041 TI - Relative sensitivity of blood and bone marrow cultures in typhoid fever. AB - In a prospective study of typhoid fever in Ahmadu Bello University Hospital, Zaria, the relative diagnostic sensitivities of blood culture and bone marrow culture were studied. The results in 64 patients with proved diagnosis of typhoid fever (either by recovery of S. typhi from stool, blood and/or bone marrow or by a positive Widal agglutination test) are presented. Forty-four per cent and 59% of the patients yielded S. typhi on blood and bone marrow cultures, respectively. In 31 patients who were investigated by both blood and bone marrow cultures, the yields of S. typhi were 35% and 61% respectively. This difference is statistically significant (P less than 0.05). In this study bone marrow culture proved to be the most sensitive diagnostic test for typhoid fever. A simple technique of bone marrow aspiration is described and its use is recommended for large general teaching hospitals. PMID- 1746042 TI - Short-stay hernia surgery with local analgesia. AB - This article documents the management of hernia operations in a Zambian General Hospital. Over a period of 28 months between 1979 and 1982, 146 patients were operated upon; 16 were managed under a general anaesthetic, eight with ketamine hydrochloride and 22 with spinal analgesia. The rest--100 patients--underwent repair with local analgesia. There were two surgical readmissions; the few who were readmitted for various other reasons have not been included. No recurrences were noted during the period of study. Morbidity was minimal and known surgical mortality was nil. PMID- 1746043 TI - Childhood tuberculosis. PMID- 1746044 TI - Safety pin in the urethra. PMID- 1746045 TI - Snake bite on the penis. PMID- 1746046 TI - Pig-bel in Nepal. PMID- 1746047 TI - Complications of methods of fracture treatment used by traditional healers: a report of three cases necessitating amputation at Ihiala, Nigeria. AB - Three fracture cases treated by immobilization with bamboo sticks by traditional bone setters ended up with amputation in a rural hospital, two for gangrene and the third for diaphyseal sequestration. Venous occlusion, followed by interruption of arterial blood supply and immobilization in a dependent position are responsible for the gangrene. Overwhelming sepsis accounted for diaphyseal sequestration in the third patient. These cases illustrate the need for more emphasis to be placed on primary surgical care, centred on rural hospitals, in the developing world. PMID- 1746048 TI - Chloroform bioactivation leading to nucleic acids binding. AB - Chloroform was bound covalently to DNA, RNA and proteins of rat and mouse organs in vivo after i.p. injection. Covalent Binding Index values of rat and mouse liver DNA classify chloroform as a weak initiator. Labelings of RNA and proteins from various organs of both species were higher than that of DNA. In an in vitro cell-free system, chloroform was bioactivated by cytochrome P450-dependent microsomal fractions, by cytosolic GSH-transferases from rat and mouse liver, and particularly by the latter enzymes from mouse lung. This observation suggests that GSH plays a role in the binding of chloroform metabolites to DNA. The presence of both microsomal and cytosolic enzymatic systems in the standard incubation mixture generally led to an additive or synergistic bioactivating effect for rat and mouse, respectively. PMID- 1746049 TI - Kaposi's sarcoma: a clinico-pathologic overview. AB - A careful overview of the classical appearances of Kaposi's sarcoma (KS) as well as of its variants were reviewed from the clinical and pathological point of view. The growth phases (stages) and the cellular patterns were histopathologically compared with emphasis on the developmental progression of disease as well as mitotic activity. Other morphological aspects were also assessed such as the features of the early phases and the incidence of hyaline bodies. One hundred and forty-three lesions from 96 patients mostly of the Italian sporadic type were investigated. A complete list of those entities which should be considered in differential diagnosis is shown and the dilemma of whether KS is a neoplasia or a hyperplasia is discussed. PMID- 1746050 TI - A hospital survey of hypocalcemia and hypophosphatemia in malignancy. AB - We evaluated the incidence of hypo- versus hypercalcemia and hypo- versus hyperphosphatemia in a survey of 158 patients with malignancy; 55/158 had bone metastases. When serum calcium levels were corrected for albuminemia, the incidence of hypo- and hypercalcemia was respectively 10.8% and 10.1%. Hypophosphatemia was found in 29.7% patients, hyperphosphatemia in 2.5%. The incidence was slightly different in presence of bone metastases. Hypocalcemia and hypophosphatemia prevailed in osteoblastic metastases and hypercalcemia in osteolytic metastases. The incidence of hypocalcemia and hypophosphatemia in malignancy was therefore surprisingly high, even apart from the presence of bone metastases. Both hypo- and hypercalcemia were associated with elevated serum alkaline phosphatase levels. Moreover, a calcium-phosphorus product reduction was observed in osteoblastic metastases, suggesting a condition of secondary hyperparathyroidism. PMID- 1746051 TI - Preliminary study on auxiliary value of serum basic fetoprotein in diagnosing lung cancer. AB - To characterize basic fetoprotein (BFP) as a new tumor marker, we measured serum levels of BFP and 5 other tumor markers (CA19-9, CEA, NSE, SCC, and TPA) concomitantly in 65 patients with lung cancer, 57 patients with benign pulmonary disease, and 40 healthy volunteers. The sensitivity of BFP was 43%, the specificity 82% and the accuracy 61%. The positivity increased in relation to stage of the disease. There was no correlation between positivity of BFP and histologic type. On the whole, BFP appeared to be analogous to TPA in terms of broad spectrum and to have an auxiliary value in diagnosing lung cancer. PMID- 1746052 TI - Leukemia and liver disease in childhood: clinical and histological evaluation. AB - Seventy-two consecutive patients with acute lymphocytic leukemia (ALL) who had undergone liver biopsy within 3 months of completing chemotherapy were studied to evaluate histological features after 2 to 3 years of chemotherapy and to correlate liver disease to the treatment schedule, the number of transfused blood units, and the identified etiology. Fibrosis due to antiblastic drugs was the most frequent histological finding. Histological liver disease was not related either to the chemotherapy schedule or the number of transfused blood units. HBV with or without delta virus and HCV infections were related to a more severe histological liver disease. In about 40% patients with chronic liver disease, no etiology was demonstrated. Immunohistochemistry revealed HBcAg in the liver of 3 HBsAg-negative patients. In conclusion, liver biopsy could be useful in patients with persistent abnormal liver function tests after the completion of chemotherapy and in patients with markers for hepatotropic virus infection. PMID- 1746053 TI - Central neurocytoma. A clinico-pathologic study of five cases. AB - Five cases of central neurocytomas are described. The tumors occurred in relatively young patients (range 14 to 43 years; mean age, 27) with no predilection for sex. All the lesions were located in the anterior portion of the lateral ventricles or in the third ventricle, involving the septum pellicidum or the fornix. Histologically, they were composed of uniform cells with round nuclei and clear cytoplasm resembling oligodendrogliomas or, to a lesser extent, ependymomas. In 4 tumors, protein cell nuclear antigen immunostaining showed a low cell proliferation rate. All cases were positive for neuron-specific enolase. Four of the 5 cases were strongly immunoreactive for synaptophysin. The immunohistochemical data were consistent with neuronal differentiation. Resection was subtotal in 4 cases and total in one. Postoperative radiotherapy was given in only one case. The follow-up revealed a good prognosis: 4 patients were alive and had a long survival (from 2 to 8 years). Only one patient died after 14 months for causes unrelated to the neoplasm. The authors emphasize the importance of immunohistochemistry to recognize this benign intraventricular tumor. PMID- 1746054 TI - Response of primary breast cancer to tamoxifen alone in elderly women. AB - The authors report on a consecutive series of 62 evaluable, elderly (age greater than 69 years) women with primary operable breast cancer treated only with tamoxifen. The treatment schedule was 160 mg on day 1 followed by a daily maintenance dose of 20 mg. Compliance to treatment was excellent, and subjective side effects were minimal. The best response achieved after at least 6 months of treatment was complete in 7, partial in 22 and minor in 3, whereas stable disease or progression was observed in 28 and 2 patients, respectively. The response rate decreased and progressions increased with time. At 6, 12, 24, 36 and 48 months of treatment, the complete + partial response rates were 30.6%, 45%, 45.6%, 38.7% and 25% and the progressive disease rates 4.8%, 19.6%, 34.8%, 45.2% and 66.6%, respectively. These results do not confirm some previous reports of a high response to tamoxifen. This difference is only partially explained by the use of mammography, which is more sensitive than palpation, to assess tumor size and treatment response. The present study does not support primary hormone therapy as a current alternative to surgery, which should be the standard treatment in otherwise healthy elderly patients with operable breast cancer. PMID- 1746055 TI - Inflammatory component: a worsening factor in locally advanced breast cancer treated by radiotherapy and systemic therapy. AB - Locally advanced and inflammatory carcinomas of the breast are two distinct entities with clear differential clinical criteria. We described a particular type of locally advanced breast cancer which, during its evolution, developed inflammatory characteristics limited to a small area of the skin. It, therefore, did not meet the common diagnostic criteria of inflammatory carcinoma. In our series, studied from December 1977 to January 1987, we treated 59 cases of locally advanced breast cancer and 105 cases of locally advanced breast cancer with an inflammatory component. The actuarial overall survival was 53.3% at 5 years and 38.4% at 7 years. Differences were observed when the two tumor types were compared. Specifically, locally advanced breast cancer with an inflammatory component had a worse prognosis, poorer survival and poorer disease-free rates than locally advanced breast cancer. PMID- 1746056 TI - Interstitial brachytherapy for carcinomas of the lower lip. Results of treatment. AB - From 1973 to 1988 47 patients with previously untreated T1 and T2 squamous cell carcinomas of the lower lip received a definitive course of interstitial brachytherapy by iridium 192 wires. The disease stage was T1 in 21 cases (44.7%) and T2 in 26, and N0 in all cases except 2 of N1. Radiation therapy dose ranged between 6000 and 8000 cGy. Local control was obtained in 44 patients (93.6%). Treatment failure in the neck was observed in 3 patients (6.7%). The 5- and 10 year actuarial disease-free survival rates were 92% and 85%, respectively. A surgical salvage was attempted in 3 patients, with postoperative definitive control of the disease in 2. The 10-year actuarial overall survival was 95%. The incidence of complications was acceptable (10.6% of mucosal necrosis). An excellent or good cosmetic result was obtained in 91.7% of patients. PMID- 1746057 TI - Autoimmune thyroiditis following interleukin-2 and LAK cell therapy for metastatic renal cell carcinoma: correlation with tumor regression. AB - A 63-year-old woman receiving recombinant interleukin-2 (rIL-2) + lymphokine activated killer cells for metastatic renal cell carcinoma developed autoimmune thyroiditis with clinical hypothyroidism and high titer anti-thyroglobulin and anti-microsomal antibodies. The onset of thyroid dysfunction was associated with tumor regression and resulted in complete response at the end of the treatment. Cytologic and cytofluorimetric studies on thyroid tissue showed two distinct populations, mainly consisting of small lymphocytes and large thyrocytes, and the latter expressed MHC class II antigens. After completion of rIL-2 treatment, hypothyroidism gradually decreased until resolution; complete tumor remission lasted 18 months. Mechanisms underlying the association between autoimmune thyroiditis and cancer regression are discussed. PMID- 1746058 TI - Definitive irradiation of nasopharyngeal carcinoma: analysis of results and failures in 103 cases. AB - During the period 1975-1984, 103 patients were treated for nasopharyngeal carcinoma. Most of them presented with an advanced stage: 64 stage IV and 26 stage III. Sixty-one patients presented with neck nodes, which was the most frequent symptom of presentation. The histologic subtypes included 64 squamous cell carcinoma and 39 undifferentiated carcinoma. All patients were treated by high energy sources with portals encompassing the primary and the whole neck. Doses ranged from 50-55 Gy in T1 patients to 65-70 Gy in T4 patients. The mean survival was 58.5 months, and 31 patients were alive and disease free at 60 months from treatment. A clear difference in survival emerged among T1, T2-3, and T4 patients (p greater than 0.01), whereas there was no significant difference between T2 and T3 patients. Also, N0 and N1 showed no significant difference in 5 year disease-free survival (38% and 41%, respectively); only 20% of N2 and 7% of N3 patients survived for more than 5 years. As regards histology, 25% of patients with a squamous cell carcinoma and 36% of those with an undifferentiated carcinoma were alive at 5 years. The presence of distant metastases (in 20 patients) was not correlated with T stage but was strongly correlated with N stage; histology did not affect the development of metastases. There clearly was no correlation between T and N stage, a behavior which probably constitutes a characteristic of these tumors. From our analysis we can affirm that N stage has a greater influence on prognosis and final outcome than T stage, at least using the UICC staging criteria. PMID- 1746059 TI - Pattern and determinants of diagnostic interval in cancers of the prostate, bladder and kidney. AB - The present study examined the pattern of presentation and diagnostic interval, i.e. number of months between first cancer symptom or sign and first medical visit, in 444 cases of urological cancer (122 of prostate cancer, 187 of bladder cancer and 135 of kidney cancer). The mean diagnostic interval was 7.6 months for prostate, 5.6 for bladder and 4.5 kidney cancer. A chance diagnosis, i.e. in absence of any symptom or sign, was reported by 16%, 8% and 18% of patients with cancer of the prostate, bladder and kidney respectively. We observed on significant differences in diagnostic intervals according to patients' demographic, sociocultural, and life-style characteristics, or tumor stage. Better quantitative and qualitative data on the pattern and determinants of delay in cancer diagnosis are clearly warranted, and the present study, although largely negative, shows the possibility of using large-scale epidemiological investigations for this purpose. PMID- 1746060 TI - Carcinosarcoma of the stomach with endocrine differentiation. A case report. AB - An unusual tumor was observed in a 67-year-old man. Microscopically, the tumor was composed of epithelial cells forming glands (CEA, EMA-positive) and spindle shaped cells (vimentin-positive). A third component was a cell population ultrastructurally characterized by intracytoplasmic granules surrounded by a membrane; these proved to be chromogranin A-positive in the immunoperoxidase study. PMID- 1746061 TI - Xanthogranulomatous cholecystitis associated with gallbladder adenocarcinoma. A clinicopathological study of 5 cases. AB - The simultaneous presence of xanthogranulomatous cholecystitis and adenocarcinoma of the gallbladder has rarely been reported. A review of 53 cases of gallbladder adenocarcinoma in a 15-year period revealed 5 cases in which a concomitant diffuse xanthogranulomatous disease was observed. Clinical and pathologic features of these cases are commented and the diagnostic importance stressed. Both inflammatory and neoplastic components were closely mixed in 3 cases, thus making a prompt diagnosis difficult. Etiologic factors implicated in the development of both entities are considered. PMID- 1746062 TI - Interferon-related leukoencephalopathy in a patient with renal cell carcinoma. AB - A 75-year-old patient with metastatic renal cell carcinoma was treated with recombinant interferon alpha-C and thereafter developed a neurologic syndrome of dementia, ataxia, confusional state, loss of concentration ability and cortical blindness. CT scan findings were compatible with leukoencephalopathy, which is reported as being a toxic effect of interferon. PMID- 1746063 TI - Fibrosarcoma of the thymic region. A case report. AB - Fibrosarcoma of the mediastinum is an unusual tumor and only few cases have been reported. We describe the clinical and pathologic findings of a case of mediastinal mass in a 34 year old woman. The histologic, histochemical, immunocytochemical and ultrastructural features of the tumor were consistent with a diagnosis of fibrosarcoma. Furthermore, the tumor displayed evidence of close relations with the thymus capsule; the possibility that it may arise from the thymic stroma is considered. The differential diagnosis of spindle cell tumors of the mediastinum is also discussed. PMID- 1746064 TI - Effect of He-O2, O2, and N2O-O2 breathing on injected bubbles in spinal white matter. AB - Injected air bubbles in spinal white matter in the rat were studied at 1 bar after decompression from an exposure to air at 3.1 bar (absolute) for 4 h. During air breathing all injected bubbles grew for the first 2 h of the observation period. Thereafter three of nine bubbles began to shrink and one of them disappeared. During breathing of heliox (80:20) bubbles consistently shrank and disappeared from view. If the breathing gas was changed from heliox to N2O-O2 (80:20), while bubbles still had an appreciable size, they started growing again. If the change to N2O-O2 was done after a bubble disappeared from view, it did not reappear. During breathing of 100% oxygen, all bubbles initially grew. Subsequently they all shrank and disappeared at about the same time after gas shift, as during heliox breathing. The effect of heliox treatment on CNS decompression sickness after air dives is discussed. PMID- 1746065 TI - Assessment of inter-rater agreement on the grading of intravascular bubble signals. AB - Transcutaneous Doppler ultrasonic bubble detectors are widely used in decompression research. However, interpretation of the complex acoustic signals from the bubble detectors involves a degree of subjectivity, and the comparability of grades assigned by different raters must be assessed. Hypothetical data were used to determine an appropriate method for evaluating the comparability of Doppler raters and to illustrate the limitations of many nonparametric statistics. Two sets of real data were then used to evaluate this procedure, the first from a training exercise carried out by Kisman and Masurel (1978, unpublished) and the second from a test tape that was independently scored by five Defence and Civil Institute of Environmental Medicine Doppler technicians. The results were analyzed by a two-stage approach. First, they were entered into contingency tables and checked for large disagreements, a tendency for one rater to grade higher than the other, and the degree of variability. Second, the results were analyzed with the nonparametric weighted kappa statistic. These studies have led to a practical, efficient method for the evaluation of Doppler raters. PMID- 1746066 TI - Psychophysiologic changes in sleep during simulated 200-m heliox saturation dives. AB - The standard polysomnogram and questionnaire were measured from 4 subjects during 2 simulated 200-m heliox saturation dives. These measurements were performed for 1 precompression night, bottom nights, 4 or 5 nights during decompression, and 1 postdecompression night. Although the subjects reported a marked decrease in quantity and quality of sleep at the bottom, only a slight degree of sleep disturbance caused by frequent awakenings was found in polysomnograms. Throughout the dive period, latency of each sleep stage, quantity of REM sleep, and the REM NREM cycle showed no changes, whereas quantity of slow wave sleep remained at a low level. From these results it was inferred that basic sleep mechanisms were not affected under 200-m heliox environment. Unusual physiologic phenomena were observed during the dive period. Intermittent diffuse rhythmic theta activity was found in 1 subject at sleep stage REM during the bottom. Rhythmic contraction of facial muscles, which was similar to bruxism, increased, particularly at sleep stage 2 in all subjects during decompression. PMID- 1746067 TI - Effects of four drugs on 4-aminopyridine seizures: a comparison with their effects on HPNS. AB - The effects of two i.v. anesthetics, Saffan and methohexitone (MHX) and two N methyl-D-aspartate receptor antagonists, MK-801 (Dizocilpine) and 2 aminophosphonoheptanoate (AP7), were tested for activity against the motor excitation (tremor, whole body jerks, and seizures) produced by the K+ channel blocker 4-aminopyridine (4-AP). Saffan increased the dose of 4-AP required for all three endpoints; MHX had no effect on tremor but reduced the 4-AP required to produce jerks and seizures. MK-801 also reduced the 4-AP dose required to produce jerking but did not affect tremor or seizures. In contrast, AP7 increased the amount of 4-AP required to produce all endpoints. The effects of these drugs on 4 AP-induced excitation are similar to their actions on hyperbaric excitation, reported by us previously, and suggest that blockade of K+ channels may contribute to the high pressure nervous syndrome. PMID- 1746068 TI - Case control study of cerebral perfusion deficits in divers using 99Tcm hexamethylpropylene amine oxime. AB - In a preliminary report, Adkisson et al. (Lancet 1989; 2:119-121) used 99Tcm hexamethylpropylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) to provide evidence for cerebral perfusion deficits in 28 cases of dysbarism. The report caused concern because these deficits were found even in cases in which the clinical manifestations were limited to the spinal cord. To address this issue further, a case-control study of cerebral perfusion using 99Tcm-HMPAO SPECT is reported. Four groups of 10 subjects were studied: a) divers scanned on average 11 days after treatment of neurologic decompression illness, b) divers scanned 3-5 yr after treatment for neurologic decompression illness, c) diver controls, and d) population controls. All groups were matched for age, and the divers were further matched for general diving experience. The scans were randomized and reported blind to history. Despite a trend toward larger numbers of deficits in individuals with decompression illness, the 4 groups were statistically indistinguishable. Furthermore, no correlation was found between the location of the perfusion deficits and the clinical presentation. These results indicate that 99Tcm-HMPAO SPECT scanning requires further evaluation before clinical significance can be ascribed to perfusion deficits found in divers. PMID- 1746069 TI - Daily diving pattern of Korean and Japanese breath-hold divers (ama). AB - Daily diving patterns and thoracic skin and sea-water temperatures were recorded during the entire work shift of Korean female unassisted (cachido) and Japanese male unassisted and partly assisted (funado) divers using Underwater Physiological Data Loggers developed in Buffalo and Japan. All 3 groups of divers were studied during the summer of 1989 and 1990. Additional studies were conducted during the winter of 1991 on Korean female divers who, unlike Japanese divers, dive all year round. The water temperature of the diving grounds in summer was 24 degrees C in both Korea and Japan, and 10 degrees C during winter in Korea. Both Korean female and Japanese male cachido divers made 113-138 dives a day and stayed in the water a total of 170-200 min.day-1, of which only 52-63 min were spent diving submerged, and the remaining time at the water surface. These diving patterns were not different between female and male cachido divers. Compared with Japanese male divers, Korean female divers dived to a shallower depth (3.7 vs. 6.9 m) with shorter dive time (29 vs. 37 s) and shorter bottom time (14 vs. 18 s). Velocities of descent (0.72 vs. 0.47 m.s-1) and ascent (0.77 vs. 0.56 m.s-1) were also slower in female divers than in male divers. The diving pattern of Korean female divers was similar in both summer and winter. Although all cachido divers wore wet suits and thus were protected from severe cold stress, thoracic skin temperature decreased during a work shift by 7 degrees C in winter (vs. 1 degree C in summer) in Korean divers. Compared with Japanese male cachido divers, Japanese male funado divers stayed in the diving ground (including time in the boat) longer (201 vs. 305 min.day-1) but performed only 23 dives per day. The average diving depth (9.7 m), duration (69 s), and bottom time for each dive (45 s), however, were significantly greater in funados. The velocity of vertical descent (1.0 m.s-1) was also significantly greater in funados because they descend with a weight (8-12 kg). The rate of ascent was not different. PMID- 1746070 TI - [First national Enantone Symposium. Progress in therapy of prostatic cancer. Multicenter study: long-term follow-up]. PMID- 1746071 TI - [LHRH analogs as monthly depot preparations in treatment of advanced prostate cancer]. PMID- 1746072 TI - [Epidemiologic and morphogenetic aspects of prostate cancer]. PMID- 1746073 TI - [Value of imaging systems in prostate cancer]. PMID- 1746074 TI - [Galenic innovation: Enantone monthly depot preparations]. PMID- 1746075 TI - [Hormone kinetics in suppression with monthly Enantone depot preparations]. PMID- 1746076 TI - Surgical ureteral injuries. PMID- 1746077 TI - Is the neodymium:YAG laser effective therapy for invasive bladder cancer? AB - The neodymium:YAG (yttrium-aluminum-garnet) laser can cause transmural coagulation necrosis of bladder tumor or bladder wall. Pathologic specimens of 18 patients prospectively treated with the neodymium:YAG laser before radical cystectomy were reviewed to compare the initial clinical stage of bladder tumor with the final pathologic stage and to assess the destructive tissue effects of neodymium:YAG laser therapy. Eleven of 18 patients were unchanged pathologically in stage of tumor or had tumor progression. Seven patients had a lower pathologic tumor stage; 3 of these patients had pathologic Stage T0 with no residual tumor, with the remainder of patients showing superficial disease. One asymptomatic small bowel injury was discovered at operation. Healing lesions showed marked granulation tissue, coagulation necrosis, and persistent ulceration. PMID- 1746078 TI - Transvaginal needle suspension procedures for recurrent stress incontinence. AB - The results of transvaginal needle suspension in 36 patients with stress urinary incontinence who failed previous operation were reviewed. Eighteen patients underwent a Stamey endoscopic needle suspension, and a Peyrera-Raz cystourethropexy was performed on the remainder. Recurrent stress incontinence was confirmed by history, physical examination, and urodynamic studies. Cure rates of 78 percent for the Stamey procedure and 83 percent for the Raz operation were achieved. Excluding patients with voiding dysfunction or urge incontinence postoperatively due to bladder instability, the failure rates were 6 percent and 11 percent, respectively. Analysis of the results according to the preoperative maximal urethral pressures demonstrated that low-pressure urethras if accompanied with urethrovesical hypermobility have no impact on the results if the anatomic abnormality was corrected adequately by the needle suspension. Thus, the transvaginal needle suspension was found to be highly effective in patients with low-pressure urethras, who failed previous operation, but had persistent bladder neck hypermobility, and suggests that this method of surgical repair should be the first choice in this selected group. PMID- 1746079 TI - Extent of bladder and ureteric involvement and urologic management in patients with enterovesical fistulas. AB - A retrospective review of hospital charts from 1978-1989 identified 21 patients with acquired enterovesical fistulas. Nine patients with fistulas secondary to benign inflammatory processes required extensive bladder resection; 2 of these had ureteric involvement. Of the 9 patients requiring extensive bladder resection, necrotic and severely inflamed bladder was excised and the bladder was closed in a multilayered fashion with absorbable sutures. An omental flap was used when possible. Postoperative bladder drainage was maintained for seven to fourteen days. Ureteral involvement was managed by stenting in 1 case and ureteroureterostomy in another. No postoperative bladder leaks or recurrent fistulas were reported. Extensive inflammatory involvement of the bladder wall may necessitate a large vesical resection. Excision of diseased bladder tissue, multilayered closure, and the use of omental interposition may help reduce postoperative complications and the risk of recurrence. Associated ureteral involvement may be present in these patients and requires urologic management. PMID- 1746080 TI - Efficacy and morbidity of "channel" TURP. AB - Transurethral resection of the prostate (TURP) is necessary in a significant proportion of men with a diagnosis of carcinoma of the prostate. Often, "channel" TURP (resection of visually obstructing tissue without extension to the prostatic capsule in a patient with metastatic or locally advanced disease to improve voiding symptoms) is required. Although several theoretical concerns regarding the efficacy and morbidity of this procedure have been voiced, data to support these contentions are lacking. In a review of 41 patients undergoing channel TURP, all were able to void following the procedure. Two patients in whom the resection was carried through the external urinary sphincter, which had been invaded by tumor, were incontinent postoperatively. Two patients had mild stress incontinence. There were no perioperative deaths. These data suggest that incontinence is higher than expected with TURP for benign disease but that results may be acceptable to the patient with significant outlet obstructive symptoms. PMID- 1746081 TI - Penile carcinoma: a twenty-five-year experience. AB - The treatment of 34 patients with carcinoma of the penis was reviewed during a twenty-five-year period (1958-1983). There were 26 patients with Stage I disease, 7 patients with Stage II, and 1 patient with Stage III disease. Among the Stage I group, 12 patients underwent partial/total penectomy and immediate ilioinguinal lymphadenectomy; 14 patients were treated with partial/total penectomy and observation of clinically nonpalpable nodes. Within the observation period, 10 of the 26 patients died, with a mean survival time of one hundred thirty-three months (standard error = 20.4), and a median of one hundred twenty months. Both the Mantel-Cox and Breslow test statistics showed the survival distribution of these groups of patients not to be significantly different from each other. All 7 patients with Stage II penile cancer died, with a mean survival time of 10.6 months (standard error = 2.1) which is significantly different from the Stage I group and the reported survival of 30-60 percent in the literature. A plan of management for the primary lesion and the role of ilioinguinal lymphadenectomy are presented. PMID- 1746082 TI - Inflatable penile prosthesis: effect of device modification on functional longevity. AB - The Scott inflatable penile prosthesis has undergone a continual evolution since its introduction in 1973. A review of 266 patients at Duke University Medical Center who received primary implantation of AMS inflatable penile prostheses from 1979 to 1988 revealed the modifications in the prosthesis have increased the functional longevity and hence the reliability of this surgical treatment for erectile impotence. PMID- 1746083 TI - Nerve conduction velocity of dorsal nerve of penis: a modified technique. AB - The dorsal nerve of the penis is involved in sexual function. Until now, the nerve conduction velocity (NCV) of the dorsal nerve of the penis has been measured by dividing the distance between the stimulating and the recording electrodes by the latency to the negative peak of the action potential. With the penis stretched with a 1 lb weight, the NCV in normal men was 33 m/sec +/- 3.8. Measuring the NCV in this way, we became aware that when we decreased the distance between the stimulating and the recording electrodes, the velocity decreased. Furthermore these different measurements were linearly related. Taking this into account, we calculated the NCV with mathematical formula. In normal people, it turned out to be faster than reported previously. PMID- 1746084 TI - Sperm quality in men with chronic abacterial prostatovesiculitis verified by rectal ultrasonography. AB - Semen analyses were performed on 50 men with chronic abacterial prostatovesiculitis (CPV) and 25 asymptomatic control subjects. All subjects had had symptoms of at least three months' duration, and the diagnosis was verified by rectal ultrasonography and after microbiologic culture of seminal plasma. Fifty-eight percent had increased concentrations of leukocytes (greater than 1 x 10(6)/mL) in the ejaculate compared with 15 percent in the controls. Only 10 percent of the CPV subjects could be classified as normospermic compared with 60 percent in the controls. The incidence of severe disturbances in sperm quality and azoospermia was also four times greater in the CPV group. Neither the degree of leukospermia nor the ultrasonographic findings could predict the extent of the disturbance in sperm quality. PMID- 1746085 TI - Ten "pearls" from my practice of penile prosthesis implantation. PMID- 1746086 TI - Traumatic stricture of prostatic urethra in ten-year-old boy. AB - Stricture of the midprostatic urethra resulted from a pelvic fracture injury in a ten-year-old boy. The stricture was successfully managed by core-through urethrotomy and transurethral resection of the scarred area in the prostate. The possible mechanism of traumatic stricture formation at such a rare anatomic location and the therapeutic options are reviewed. PMID- 1746087 TI - Modification of flip-flap technique for correction of distal penile hypospadias. AB - Flip-flap is a popular technique used for correction of distal penile hypospadias. When the flap length is more than 2 cm, meatal stenosis may develop postoperatively. This stenosis is probably due to the ischemia at the tip of the flap. We have used flaps with wide base to ensure good blood supply to avoid this complication. The results were excellent in all of the cases in which this modification was used. PMID- 1746088 TI - Crossed solitary renal ectopia. AB - A boy being followed for cardiovascular anomalies was found at age fourteen to have a solitary right kidney which drained to the left side of the bladder. We have reviewed the reports of 33 patients with solitary crossed renal ectopia which describe many associated congenital anomalies especially in the genitourinary and skeletal systems. We found no description of associated cardiac anomalies. We review the literature on solitary crossed renal ectopia and describe an additional case. PMID- 1746089 TI - Hemorrhagic myelolipoma of adrenal gland after blunt trauma. AB - A case of adrenal myelolipoma is reported in a patient in whom symptoms of hematuria and flank pain developed after the patient had sustained blunt trauma. Adrenal myelolipomas are usually found incidentally at autopsy. However, the symptomatic presentation of this patient was probably caused by traumatic intratumor hemorrhage. The etiology and pathogenesis of these tumors are discussed in relation to their occasional symptomatic presentation and to their differential diagnosis. PMID- 1746090 TI - Type IX Ehlers-Danlos syndrome: bladder diverticula with transitional cell carcinoma. AB - Patients with type IX Ehlers-Danlos syndrome have a tendency for development of diverticulae of the urinary bladder, and these often recur after surgical excision. We report on a patient with this syndrome in whom an extensively infiltrating transitional cell carcinoma developed in a diverticulum. To our knowledge, this is the first reported case of malignancy developing in a patient with type IX Ehlers-Danlos syndrome. The highly aggressive nature of the neoplasm is discussed in relation to the dampened desmoplastic response to the tumor, observed in this patient. PMID- 1746091 TI - Fatal transitional cell carcinoma of bladder in renal transplant recipient. AB - The risk of development of a malignancy as a consequence of long-term immunosuppression is well documented. Herein, we report the course of a renal allograft recipient in whom a fatal transitional cell carcinoma of the bladder developed eighteen years following transplantation. PMID- 1746092 TI - Effects of high-energy shock waves on murine renal cell carcinoma. AB - The effects of high-energy shock waves (HESW) on a murine renal cell carcinoma (RenCa) was investigated. In vitro exposure of tumor cells to HESW resulted in a dose-dependent reduction in cell viability as determined by trypan blue dye exclusion, plating efficiency, growth curve, and soft agar clonogenic assays. Activity of lactic dehydrogenase (LDH) was detected in the supernatant after the HESW treatment due to cellular destruction, and a dose-dependent increase in cytocidal effect was demonstrated. Ultrastructural changes with swelling and distorted cristae of mitochondria, vacuolation, ribosomal lysis, and chromatinolysis were observed in HESW-treated RenCa cells. Flow cytometric (FCM) study revealed that DNA content of RenCa cells diminished after 200 HESW treatment, and RNA content of tumor cells decreased markedly after 400 HESW treatments. Partial or complete inhibition of tumor growth was shown in both animal modalities of subcutaneous inoculation and intravenous injection with sequential lung metastases. This study stressed again that HESW may play a role in combinational protocol for the treatment of human renal cell carcinoma in certain circumstances. PMID- 1746093 TI - Seventy-eight-year-old woman with hematuria, hypertension, and flank bruits. PMID- 1746094 TI - Simultaneous renal and transitional cell carcinomas in same kidney with subsequent lymph node metastasis: DNA flow cytometric study. AB - We report the DNA content in simultaneous renal and papillary transitional cell carcinomas in the same kidney with a subsequent metastasis of the transitional cell carcinoma to a left supraclavicular lymph node. The flow cytometric DNA analysis revealed aneuploid stemlines with identical DNA indices in both the transitional cell carcinoma and the metastatic lesion and a diploid pattern in the renal cell carcinoma. A discussion of these findings and the potential implication of DNA ploidy analysis in similar situations is presented. PMID- 1746095 TI - Efficacy and tolerance of norfloxacin in treatment of complicated urinary tract infection in outpatients with neurogenic bladder secondary to spinal cord injury. AB - We studied the efficacy of a fourteen-day course of the fluoroquinolone, norfloxacin, in a group of 69 catheter-free spinal cord injury (SCI) outpatients who experienced a total of seventy-nine urinary tract infection (UTI) episodes. A total of 114 bacterial strains representing twenty species, including sixteen Pseudomonas aeruginosa, all susceptible to norfloxacin, were isolated from initial urine cultures. Mid-treatment cultures in 58/79 (73%) cases were negative. Cultures taken five to seven days after completing treatment in 42 cases (53%) were negative. In the remaining 37 there was persistence of initial or superinfecting pathogen(s), or early reinfection with new organisms. Cultures eight to twelve weeks later in 32 cases with initial eradication showed that 27 (84%) had either relapsed and/or become reinfected. Clinical cure occurred in 4/6 (67%) symptomatic episodes. Side effects occurred in 6 of 73 (8%) patients who received norfloxacin, 4 of whom required withdrawal from the study. Twenty of one hundred twenty-two (16%) bacterial strains isolated during or after treatment were resistant to norfloxacin. Given the limited oral treatment options and the constant risk of reinfection in the SCI population, norfloxacin appears to be a reasonable choice in many patients. However, as with other antimicrobials, when using norfloxacin in SCI patients, the emergence of resistant bacteria must be carefully monitored. PMID- 1746096 TI - [Relation between cervical mucus sperm toxicity and pregnancy in cows]. AB - Cervical secretion was collected from 99 dairy cows of the Black Pied Lowland breed at an age of 24 to 109 months with a minimum performance of 4000 kg of milk annually in spontaneous oestrus 42 days post partum at the minimum. It was demonstrated by the radioimmunological determination of progesterone in skim milk that from all the breeding cows (n = 99) the oestral secretion was collected during an optimum insemination time (x = 0.19 ng.ml-1 progesterone). Of the statistical set of 99 cows, 55 (i.e. 56.57%) got in calf and 43 (i.e. 43.43%) remained barren. As found, the conception results were not influenced by the rank of the insemination after parturition and the conception capacity of the cows was not influenced by the length of time from parturition to the respective inseminations. It was demonstrated in our investigation that the conception capacity of the cows increases as the time of sperm survival prolongs in the cervical secretion in vitro. The highest conception capacity (80%) was recorded in the cows whose cervical secretion was free of spermiotoxic action. In such cases the motility of the spermatozoa in the oestral mucus was maintained at a temperature of 38 degrees C for longer than 300 minutes. On the other hand, it was demonstrated that the conception capacity of the cows declines with shortening time of sperm survival in the cervical mucus. PMID- 1746097 TI - [Glycemia and glycosuria in the search for new energy sources for calves]. AB - Monosaccharide (glucose), disaccharide (saccharose hydrolysate) and polysaccharide (maltodextrin KMS-X 70) were administered perorally to the calves of three age categories (pre-rumination, transition, rumination period) after 12 hour fasting. The following characteristics were investigated: glycaemia, glycosuria, lactic acid concentration, plasma osmolality, hematocrit value, net acid-base secretion and excrement dry matter. The degree of saccharide utilization was evaluated from glycaemia, glycosuria and clinical condition. The administration of maltodextrins to calves at the age of two to three weeks was not found convenient. The absorption of saccharose (hydrolyzate depended strongly on age. The saccharose hydrolyzate dose of 2.5 g per kg l. w. was calculated with respect to glycaemia and glycosuria, but not to the excrement dry matter content. In comparison with glucose absorption, saccharose hydrolyzate seems to be a convenient energy source for calves of different age categories. PMID- 1746098 TI - [Dynamics of changes in thyroxine levels in castrated newborn calves]. AB - Changes in thyroxin levels were studied in calves castrated just after birth. The changes in thyroxin concentration in the blood serum were studied until the eighth day of life of the calves and the weight gains were monitored until weaning at an age of 90 days. In the experimental group, lower thyroxin levels were first recorded in the third hour post natum and were observed to persist until the eighth day; except for three hours the decrease was not statistically significant. Neither were any significant differences observed in the average daily gains in both groups of calves. Treatments like non-surgical castration in newborn calves do not elicit extreme stress reactions that would be conducive to disorders of health and vitality. PMID- 1746099 TI - [Use of chick embryos for prediction of embryotoxic effects of mycotoxins in mammals]. AB - Embryotoxic effects of 25 mycotoxins were investigated in two-, three- and four day chick embryos; the results were evaluated on the eighth day of development. The embryotoxicity ranged from 0.0001 to 0.1 microgram per embryo in T-2 toxin, aflatoxin B1, G1, B2 and M1, cytochalasin E, ochratoxin A and PR-toxin; from 0.1 to 1.0 microgram per embryo in sterigmatocystin, aflatoxin G2, vomitoxin (4deoxynivalenol), patulin, rubratoxin B, secalonic acid D, mycophenolic acid, and from 1.0 to 100 micrograms per embryo in penicillic acid, cyclopiazonic acid, tenuazonic acid, citrinine, brevianamide A, zearalenone, fusaric acid, griseofulvin, kojic acid and 8-methoxypsolaren. Acute cardiotoxic effects were observed in PR-toxin, patulin, rubratoxin B, penicillic acid, citrinine and zearalenone. Teratogenic effects with a spectrum of different embryonal malformations occurred in T-2 toxin, ochratoxin A, PR-toxin, patulin, secalonic acid D, mycophenolic acid and citrinine. The embryotoxic effects demonstrated in chick embryos correlated with the well-know literary data on mammals. Considering the different chemical composition and biological effects of mycotoxins, we suppose that the embryotoxicity test of chick embryos will also be suitable for testing other biologically active substances in the environment. PMID- 1746100 TI - [Pathogenicity of Tetratrichomonas gallinarum]. AB - Eight axenic strains of Tetratrichomonas gallinarum were isolated from the caeca or cloacae of ducks and geese. Different growth curves were determined for each of the strains and the generation times were calculated, ranging from 2 h 36 min to 4 h 44 min. The axenic cultures of seven T. gallinarium strains were subjected to the Honigberg test on inbred mice. The average volumes of the six-day-old subcutaneous abscesses ranged from 129.98 to 185.63 mm3. Selected strains of trichomonads were used for experimental infection of ducks and geese. Neither the macroscopis examination nor the microscopic analysis did find any greater pathological changes in the mucosa of the caecum of the birds, though the Trichomonas organisms were observed in large quantities among the villi in the crypts. It is believed on the basis of the results that the species T. gallinarium carries no primary pathogenicity to the specific hosts. PMID- 1746101 TI - Isolation of Actinobacillus seminis from rams in the United Kingdom. AB - Actinobacillus seminis was isolated from the semen of five rams on four farms. Four of the rams had abnormal semen and three were also infertile. The isolates of A seminis showed similar phenotypic profiles and electrophoretic protein patterns to the type strain of A seminis but were distinct from Histophilus ovis previously isolated from rams with epididymitis in Scotland. The infection appeared to be subclinical but two of the five rams had palpable abnormalities of their testes. Three rams were treated with antibiotics but the infection persisted. No gross lesions were found in the genitalia of two of three rams examined post mortem but one had necrotic abscesses in the testes and epididymis. A seminis was isolated from the seminal vesicles and epididymis of one ram without gross lesions but not from the genitalia of the other two. On one farm the infection in a recently purchased ram led to the detection of another case as a result of the bacteriological screening of 11 stock rams not in contact with the initial case. These five subclinical cases, which included a supposedly healthy stock ram, suggest that A seminis infection may be widespread and should be considered in cases of infertility. PMID- 1746102 TI - An atypical case of lymphosarcoma (sporadic bovine leukosis) in a heifer. AB - An 18-month-old Friesian heifer had several unusual, raised, black, cutaneous plaques, some of which were up to 20 cm in diameter, on its head and neck, limbs, thorax and perineum. There was also generalised lymphadenopathy. A clinical diagnosis of lymphosarcoma (sporadic bovine leukosis) was derived from a fine needle aspiration of a skin lesion. Post mortem and histological examinations confirmed a multicentric lymphosarcoma with widespread infiltration into many of the tissues recognised as predilection sites for this type of tumour. However, in the authors' experience, the presence of tumour masses in the trachea and the right mainstem bronchus was atypical. PMID- 1746103 TI - Poisoning of cattle fed ergotised silage. PMID- 1746104 TI - Microscopic agglutination: a rapid test for identification of Treponema hyodysenteriae. PMID- 1746105 TI - Experimental inoculation of sheep with Borrelia burgdorferi. PMID- 1746106 TI - Enterococcus hirae infection and focal necrosis of the brain of chicks. PMID- 1746107 TI - Origin and eradication of the North African outbreak of New World screw-worm. PMID- 1746108 TI - Withdrawal of terodiline hydrochloride. PMID- 1746109 TI - Cardiac failure in beef cattle fed dried poultry litter. PMID- 1746110 TI - Feline miliary dermatitis. PMID- 1746111 TI - Videoendoscopic laser surgery in horses. PMID- 1746112 TI - Controls on blue-eared disease relaxed. PMID- 1746113 TI - Risks of sheep vaccination explained. PMID- 1746114 TI - Analgesic and spasmolytic effects of dipyrone, hyoscine-N-butylbromide and a combination of the two in ponies. AB - The analgesic and spasmolytic effects of dipyrone (Novalgin) (2500 mg/100 kg bodyweight) hyoscine-N-butylbromide (Buscopan) (20 mg/100 kg bodyweight) and a combination of both drugs were evaluated in a balloon-induced model of colic, using five ponies with caecal fistulae. The drugs were given intravenously and 0.9 per cent sodium chloride solution (5 ml/100 kg bodyweight) was used as a control. The physiological saline solution and dipyrone had no effect on caecal contractions. After the injection of hyoscine-N-butylbromide and the drug combination caecal contractions ceased within 30 seconds and for 20 and 24 minutes, respectively (P less than 0.05). The results on pain relief were not statistically significant for any of the drugs. Dipyrone had a good analgesic effect in only two of the ponies, starting after eight to 10 minutes and lasting for 50 minutes. The drug combination relieved pain within 30 seconds after injection and the relief lasted for 50 minutes in three of the ponies and for 20 minutes in the other two. Hyoscine-N-butylbromide alone produced an analgesic effect within 30 seconds after injection which lasted for 20 minutes. PMID- 1746115 TI - Aortic valvular dysplasia in a calf. AB - Aortic valvular dysplasia, a congenital abnormality not previously reported in cattle, was diagnosed in a calf with a pulsating mass at the base of its neck, an enlarged area of cardiac dullness and a loud (grade IV/V) systolic cardiac murmur. Electrocardiography and thoracic radiography demonstrated that the left atrium and ventricle were enlarged. Dysplasia of two aortic valve cusps and post stenotic dilatation of the ascending aorta were identified by echocardiography and confirmed post mortem. PMID- 1746116 TI - Sensitisation of cattle to bovine and avian tuberculins with Mycobacterium cookii. PMID- 1746117 TI - Ovine and caprine babesiosis in Iran: treatment with imidocarb. PMID- 1746118 TI - Mitochondrial alterations in skeletal muscle in a bovine encephalopathy. PMID- 1746120 TI - Tattooing pit bull terriers. PMID- 1746119 TI - Homoeopathic remedies. PMID- 1746121 TI - Toxocariasis campaign. PMID- 1746122 TI - BSE and potential risks to slaughtermen. PMID- 1746123 TI - Additional algal toxicosis hazard. PMID- 1746124 TI - Enterotoxaemia in dogs. PMID- 1746125 TI - Enterococcus hirae in different animal species. PMID- 1746126 TI - Control of bird leeches. PMID- 1746127 TI - Facial swelling in cattle. PMID- 1746128 TI - A simple test for mothball component differentiation using water and a saturated solution of table salt: its utilization for poison information service. AB - All 651 cases of mothball ingestion received by a poison information center were studied. At each time of inquiry, the staff member asked the caller to test whether the mothball floated or sank in water and a saturated solution of table salt. With the results of the test the staff member identified the mothball ingredient. Though most of the callers were housewives with little knowledge of medicine, the differentiations were each completed within 5 min. Later, gas chromatographic analyses revealed that no errors in differentiations had been made. Our method proved a quick preliminary test for mothball component differentiation in poison information service. PMID- 1746129 TI - Effects of prenatal pyrethroid insecticide exposure on the sexual development of rats. AB - The prenatal effects of exposure to the insecticide cyhalothrin on the sexual maturation and sexual behavior of rats were investigated. Female rats were dermally treated with 1 ml/day of 0.02% (w/v) aqueous cyhalothrin solution or its vehicle throughout pregnancy. This insecticide administration delayed the age of testicle descent but did not modify the age of vaginal opening. In adulthood, both male and female rat sexual behaviors were not different from vehicle-treated animals. It was concluded that prenatal exposure to cyhalothrin can induce alterations in the development of certain physical characteristics of rats which are not correlated with functional deficiencies in the animals' later life. PMID- 1746130 TI - Cardiovascular effects in bonnet monkeys (Macaca radiata) of a cassava-based protein-deficient diet. AB - Bonnet Monkeys (Macaca radiata) were maintained for up to 5 mo on protein deficient diets that contained tapioca starch (cassava starch) as the source of carbohydrate. The animals developed mucopolysaccharidosis of blood vessels and cardiomyopathic changes in the heart. These changes were similar to the mucoid vasculopathy and cardiomyopathy seen in Kerala where tapioca is consumed as a staple diet by a large proportion of the people. The lesions were enhanced by longer duration of feeling the diet and in protein-deficient animals given additional amounts of tapioca starch. This indicates that protein-carbohydrate malnutrition does play a role in the induction of such cardiovascular disorders. PMID- 1746131 TI - Mineral profile of serum in experimental copper intoxication of sheep from industrial emissions. AB - We studied the dynamics of Cu, Fe, Zn, Mo, As, Cd, Pb and Se in the serum of sheep during experimental copper (Cu) intoxication from emissions from a Cu factory. From the food and the dosed emission, the daily intake was 466.8 mg Cu, 1253.93 mg Fe, 11.67 mg Zn, 0.74 mg Mo, 34.75 mg As, 0.091 mg Cd, 2.13 mg Pb, and 2.57 mg Se/experimental ewe. After the onset of Cu intoxication the first ewe died on the 65th d and the last one on the 84th d of the experiment. Hypercupremia was observed from the 50th d after the beginning of emission administration. Significant changes were observed in serum Cu on the 50th, 70th and 77th d (P less than 0.01). Changes in the dynamics of the other elements were recorded at the end of the cumulative phase and during the hemolytic crisis by also determining Fe, Zn, Mo, As, Cd, Pb and Se in serum of the Cu-poisoned sheep. PMID- 1746132 TI - 2,4-D toxicosis. I: A pilot study of 2,4-dichlorophenoxyacetic acid- and dicamba induced myotonia in experimental dogs. AB - English Pointer dogs dosed po with encapsulated 2,4-dichlorophenoxyacetic acid (2,4-D) or 2-methoxy-3,6-dichlorobenzoic acid (dicamba) developed varying degrees of myotonia. Dogs given 175 or 220 mg of 2,4-D/kg body weight rapidly developed clinical and electromyographic (EMG) manifestations consistent with a diagnosis of myotonia or pseudomyotonia. Dogs given 2,4-D at 86.7, 43.7 or 8.8 mg/kg body weight developed subclinical manifestations of myotonia detectable only with an electromyograph. The administration of 2,4-D at 1.3 or 1.0 mg/kg body weight failed to produce detectable EMG changes. One dog given dicamba at 86.7 mg/kg body weight developed clinical and EMG manifestations of myotonia similar to those induced by the highest doses of 2,4-D. PMID- 1746133 TI - Increased serum sulfate concentrations in man due to environmental factors: effects on acetaminophen metabolism. AB - Serum sulfate concentrations were determined in volunteers consuming municipal drinking water with varying sulfate contents--77 ppm in Saskatoon and 1157 ppm in Rosetown. The serum sulfate concentrations were subsequently monitored after the administration of single or multiple-dosing regimens of acetaminophen, which undergoes sulfoconjugation, to determine whether sulfate concentrations in serum changed. Average serum sulfate concentrations were 0.35 mmol/L (Saskatoon) and 0.50 mmol/L (Rosetown). Saskatoon volunteers had a significant fall in serum sulfate concentrations during the multiple-dosing regimen. This was not seen in the Rosetown participants. The rates of urinary excretion and renal clearance of sulfate were significantly higher in the Rosetown volunteers. Except for the multiple-dosing t1/2 levels, the Cmax, tmax, AUC and Cl/f of acetaminophen were not significantly different within or between the 2 groups. The excretion of sulfate and glucuronide conjugates of acetaminophen was not significantly different between the 2 groups, but there was a difference within each group with respect to single and multiple-doses. Excretion of the sulfate conjugate fell significantly in the Saskatoon volunteers during the multiple-dose portion of the study, whereas the percentage excreted as the glucuronide increased. The consumption of 15-fold greater sulfate levels in drinking water increased the sulfate concentration in serum. However, this increased concentration did not significantly alter the sulfoconjugation of acetaminophen. PMID- 1746134 TI - 2,4-D toxicosis.II: A pilot study of clinical pathologic and electroencephalographic effects and residues of 2,4-D in orally dosed dogs. AB - English pointer dogs dosed po with encapsulated 2,4-dichlorophenoxyacetic acid (2,4-D) at 1.3, 8.8, 43.7, 175 or 220 mg/kg body weight failed to exhibit abnormalities in hematologic, serum biochemical, urinalysis, or electrocardiographic parameters. At the 3 lowest doses, no changes were noted in electro-encephalograms (EEGs). In the dog given 175 mg/kg, at 24 h postdosing mild sedation was accompanied by excessive slowing in the EEG with loss of low voltage fast activity. In the dog given 220 mg/kg, nonspecific alterations in the EEG suggestive of irritation and mild seizure activity was detected 7 h, but the EEG returned to normal by 24 h. A maximum 2,4-D concentration in serum of 1075 ppm was detected 5 h after a po dose of 220 mg/kg. A maximum 2,4-D, concentration in urine of 1792 ppm was detected 2 h after a po dose of 175 mg/kg, while 25 h after that dose kidney issue contained 271 ppm. PMID- 1746135 TI - Modification of an automated method for determining plasma and erythrocyte cholinesterase activity in laboratory animals. AB - By altering the analytical parameters on an automated analyzer, analytical precision for measuring cholinesterase (ChE) activity in hemolysates was markedly improved in samples from several species. Manual and automated spectrophotometric analyses of plasma and erythrocyte ChE activity were optimized for use in rats, mice and dogs. Replicate ChE analyses were performed on plasma samples and on hemolysates made from whole blood or packed erythrocytes to determine the precision of the manual ChE method and 4 modifications of the automated method. Large method-related differences in precision were observed for the erythrocyte assay, but not the plasma assay. The addition of a nonionic detergent to make hemolysates was beneficial in determining erythrocyte ChE activity in the rat, but not in the mouse or dog. Species specific temperature conversion factors were necessary for comparing results from methods using different analytical temperatures. Analysis of whole blood hemolysates provided similar or better precision for determining erythrocyte ChE activity compared to using hemolysates made from packed erythrocytes. Comparisons of erythrocyte ChE results obtained from assays with even minor methodological differences should be approached with caution because of the many analytical factors which can affect results. PMID- 1746136 TI - 2,4-D toxicosis.III: An attempt to produce 2,4-D toxicosis in dogs on treated grass plots. AB - Eighteen English pointer dogs were randomly assigned to 3 outdoor grass-plot enclosures (6/enclosure) uniformly sprayed once with either the 2,4 dichlorophenoxyacetic acid (2,4-D) dimethylamine formulation (DMA-4) at the maximum recommended application rate, DMA-4 at 4 times the maximum recommended application rate, or the DMA-4 vehicle alone at 4 times the maximum recommended application rate. A heavy rain shower occurred 24 h after application. The dogs were observed for clinical signs and evaluated using an electroencephalograph, electrocardiograph (lead I), and electromyograph prior to exposure, and either 1 or 7 d after continuous exposure. Clinical examination, hematologic and serum biochemical data were obtained, and serum, urine and kidney 2,4-D were quantified. Half of the dogs from each group were killed after 1 d of continuous exposure, while the other half were killed after 7 d. Gross postmortem and histologic examinations were conducted on each dog. No obvious 2,4-D effects were detected in any of the dogs. PMID- 1746137 TI - Pharmacological reactivity of rat vas deferens in chronic and subacute lead intoxication. AB - The influence of subacute and chronic lead intoxication on the responsiveness of the rat was deferens was investigated by determining pD2 and relative responsiveness ratio (p) values for noradrenaline and for acetylcholine. Thus, the pD2 values of noradrenaline and acetylcholine from vas deferens of lead treated rats were greater than those from normal rats, indicating that lead, in the dose and periods of treatment utilized, provoked a rise in vas deferens sensibility to noradrenaline and acetylcholine. Since it is known that the chirurgical or chemical denervation of the sexual ducts also provokes hypersensitivity, it may be suggested that this would be a possible mechanism for the observed alterations. A local lead toxic effect on the smooth muscle or at the level of androgen receptors should also be considered. PMID- 1746138 TI - Brachiaria decumbens toxicity--grass or fungus? PMID- 1746139 TI - Neuropathological effects and deaths of cattle and sheep in Argentina from Phalaris angusta. AB - Neuropathological disorders and mortality occurred in cattle and sheep grazing P angusta. This native plant of South America is frequently found as a good quality component of natural pastures. Cattle and sheep feeding in pastures where P angusta was dominant started dying or showing signs 3 to 5 d after rain-falls started following a period of drought. Some animals died suddenly, while others nervous effects( incoordination, inability to walk normal, recumbency) and death for up to 2 w after the beginning of the signs. Postmortem findings were bilaterally symmetrical, greenish pigmented areas in the grey matter of the brain stem and diencephalon. A greenish tinge was also noted between the cortex and the medulla of the kidneys. Granules of a brown pigment were noted within the cytoplasm of neurons. An alkaloid substance was detected in the plant. Morbidity was 2.3 to 10.5% in herds B and A, and 0 to 3.4% in flocks D and C, respectively. Mortality was 0.8 to 1.0% in herds B and C, and 3.4 to 11.7% in flocks D and C, respectively. P angusta behaves, in terms of toxicity, as other Phalaris spp. Its widespread distribution in areas of extensive grazing poses a threat to cattle and sheep production in Argentina. PMID- 1746140 TI - Snake venom constituents: biochemistry and toxicology (Part 1). AB - Complicated and mystifying as the snake envenomation process may appear, the toxic principles of snake venoms are biochemical entities that could be isolated, purified and characterized. In this review, the toxicological process of envenomation and the biochemical basis of venom toxicity are presented for those not directly involved in venom research but who nevertheless have an interest in snake venom poisoning. PMID- 1746141 TI - Collective human food poisonings by clenbuterol residues in veal liver. AB - Twenty-two patients were reported to complain of tremor, headaches, tachycardia and dizziness 1-3 h after eating veal liver. As clinical symptoms were not suggestive of an infectious cause, the presence of veterinary drug residues was suspected. Clenbuterol, a beta 2-agonist, was being illegally used in cattle because of its anabolizing properties and may explain the observed effects. Assays of clenbuterol in samples of veal liver showed concentrations of 0.375 and 0.500 micrograms/g. To our knowledge, this is one of the first reports of clinical symptoms in humans associated with the consumption of veterinary drug residue-containing food. PMID- 1746142 TI - Acid-base balance in alcohol users seen in an emergency room. AB - Over 10% of emergency room patients are diagnosed as having alcohol (6.0%) or drug intoxication. In the present study 196 alcohol intoxications treated in a hospital were studied retrospectively; 49.2% of the patients had abnormal acid base values, alcoholics more often than non-alcoholics (p = 0.04). Mean blood ethanol concentration (BAC) was 310 mg/dl (SD 120); alcoholics had higher concentrations of alcohol. BAC was the higher the lower the serum pH was (p less than 0.002, r = -0.45). The deeper the coma the lower the serum pH (p less than 0.05) and the higher the BAC (p less than 0.0001). Respiratory acidosis (31.7%) was an important finding in those intoxicated. Metabolic acidosis (7.9%) could be explained by the presence metabolites of ethanol in the serum and by decreased extra-cellular fluid volume. Metabolic alkalosis related to vomiting and an extra cellular fluid volume decrease was found in 7.9% of the patients. Respiratory alkalosis was a rare finding (1.6%). Hypokalemia (22.5%) and hypernatremia (15.3%) were the most important electrolyte changes. Chronic alcoholics had lower serum potassium than had non-alcoholics; 3.6% (n = 7) of the patients had to be intubated. Acid-base disturbances were frequent in adults with alcohol intoxication. Serum pH correlated well with the state of consciousness and the BAC. PMID- 1746143 TI - Correlation of serum ibuprofen concentration with clinical signs of toxicity in three canine exposures. AB - The clinical signs and serum concentrations of ibuprofen are reported for 3 canine exposures. No adverse clinical signs or abnormal laboratory parameters were observed when serum ibuprofen concentrations were less than 31 micrograms/mL. Melena and 38 mg blood urea nitrogen/dL (normal 7-26 mg/dL) were present in an animal with a serum ibuprofen of 138 micrograms/mL. PMID- 1746144 TI - Interactions between copper and selenium in sheep in the course of experimentally produced copper intoxication. AB - This work evaluated the effect of interactions between copper (Cu) and selenium (Se) in the course of experimentally-produced Cu intoxication with industrial emissions on the animals' life spans and the Cu and Se concentrations in serum, liver and kidneys. We selected 15 Valaska ewes 1.5 y old. After the morning feeding all the animals were given emissions from a nearby Cu plant that contained 16.5% Cu and 0.0093% Se. Seven of the animals (group B) were given 5 ml SELEVIT injectable (Biotika, Slovenska Lupca)/head before starting the experiment and again on days 30 and 60. In the animals without Se supplementation (group A) the daily Cu and Se intakes from the emission and food were 466.0 mg and 2.56 mg, respectively. The average life span of the sheep in group A was 77 d and in group B it was 79.83 d. The first death due to intoxication occurred on the day 65 in group A and on day 69 in group B. During the emission feeding period no statistically significant differences were observed in cupraemia between the ewes with Se supplementation and those without it. Hypercupraemia was found in both groups from day 50 till death. Only at the end of the experiment was the serum Cu of group A statistically lower than that in group B. Cu concentrations in the liver and kidneys (dry matter) of the sheep that died with Cu intoxication in group A was 2138 +/- 1090.96 mg/kg and 272.94 +/- 197.16 mg/kg, and in group B they were 2603 +/- 1332.9 mg/kg and 341.65 +/- 307.45 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746145 TI - An outbreak of lupinosis in sheep. AB - Lupinosis is a mycotoxicosis caused by the ingestion of toxins produced by the fungus phomopsis leptostromiformis which grows on lupin plants. An outbreak of natural lupinosis in lambs occurred in Caceres, Spain. Clinical signs were inappetence, depression, constipation, weakness and different degrees of jaundice. Blood samples were analysed every 7 d for 5 w for hematocrit, total protein, glucose, total bilirubin, and GOT, GPT and alkaline phosphatase activities. The last 4 parameters were increased and returned to normal values after 2-3 w. The liver was swollen and a bright yellow color; microscopically fatty metamorphosis, necrotic areas and infiltration of polymorphonuclears were observed. This is the first time that lupinosis is described in Spain. PMID- 1746146 TI - Eosinophilia, lead poisoning and Toxacaris canis infection in children. AB - This report identifies Toxacaris canis infestation as a frequent cause of eosinophilia in both lead-poisoned and nonlead-poisoned children. An overall prevalence of 23% was recorded. Literature reveals a vast difference in regional prevalence of T canis infestations and emphasizes the need for the practitioner to be aware of the community in which he/she practices. Because of the adverse neuropsychological effects from T canis infestations, doctors in areas where there is a high prevalence of the disease should consider screening for infestations and conducting psychological testing of infested children. PMID- 1746147 TI - Investigating oiled birds from oil field waste pits. AB - Procedures and results of investigations concerning the oiling of inland raptors, migratory water-fowl and other birds are presented. Freon washings from the oiled birds and oil from the pits were analyzed by gas chromatography. In most instances the source of the oil could be established by chromatographic procedures. The numbers of birds involved (including many on the endangered species list) suggested the need for netting or closing oil field waste pits and mud disposal pits. Maintaining a proper chain of custody was important. PMID- 1746148 TI - Subchronic toxicity studies of tri-n-butyltin and triphenyltin acetates in rats. AB - The effects of a moderate but prolonged exposure of rats to tri-n-butyltin acetate (TBTA) and triphenyltin acetate (TPTA), as might be encountered as residues in yam peel diets, were investigated in rats. These subchronic toxicity studies (16, 8, or 4 mg TBTA/kg and 20, 10 or 5 mg TPTA/kg) showed histopathologic lesions in lungs, liver, intestine and kidney. The hematologic parameters in the groups treated with either compound fell within the normal range for the rats. However, there was a reduction in mean lymphocyte count for rats receiving 10 or 20 mg TPTA/kg, and a reduction in monocyte count in the 20 mg TPTA/kg group. These data indicate a need for further toxicologic studies and cautionary measures to avoid ingestion, inhalation or contamination of dietary materials by these fungicides. PMID- 1746149 TI - Livestock poisoning from oil field drilling fluids, muds and additives. AB - The use and potential toxicity of various components of oil well drilling fluids, muds and additives are presented. Many components are extremely caustic resulting in rumenitis. Solvent and petroleum hydrocarbon components may cause aspiration pneumonia and rumen dysfunction. Some additives cause methemoglobinemia. The most frequently encountered heavy metals are lead, chromium, arsenic, lithium and copper. Considerations for investigating livestock poisoning cases and several typical cases are reviewed. PMID- 1746150 TI - Venomous arthropods. PMID- 1746151 TI - Evaluation of a commercial immunoassay system for sulfamethazine and aflatoxin detection in biological fluids and feeds. AB - Commercial immunoassay systems produced by International Diagnostics to analyze for sulfa drugs and aflatoxin residues have been evaluated with milk, urine, feed and serum samples. Neither system produced satisfactory results with feeds. The sulfa test reproducibility was good enough to provide semiquantitative results on milk (40 ul sample) and urine, but should be regarded as qualitative on urine or feed. The reproducibility of the aflatoxin test was acceptable for semiquantitative use on serum, but should be regarded as qualitative on urine and semiquantitative on milk with a solid phase concentration. The overall reproducibility was at least +/- 10% if the test was used semiquantitatively. The sensitivity of the test was 10 ng for both sulfamethazine and aflatoxin B1. The range of the color change was very narrow (0-20 ng). The aflatoxin test was designed for aflatoxin B1 and was roughly twice as sensitive to B1 as to M1 aflatoxin. These procedures can be used on appropriate matrices at suitable sensitivities to rapidly screen samples for sulfa drugs and aflatoxin residues. The use of proper standards to demonstrate effectiveness in each matrix is very important. PMID- 1746152 TI - Histopathology of the early phase during experimental Corynebacterium pseudotuberculosis infection in lambs. AB - Histological responses during experimental Corynebacterium pseudotuberculosis infection in lambs were investigated in parotid lymph nodes for ten days following inoculation. Lambs were infected by the subcutaneous route into the right eyelid with a virulent strain of C. pseudotuberculosis. Multiple microscopic acute abscesses, predominantly infiltrated with polymorphonuclear (PMN) leucocytes, were seen in the right parotid lymph node on the 1st day post inoculation (PI). This massive PMN infiltration coincided with a peripheral blood granulocytosis. On day 3 PI, an influx of histiocytes was observed, while the microabscesses became confluent. From day 3 to day 10 PI, these lesions became enlarged and transformed into typical pyogranulomas with a central necrosis and a peripheral mantle of mononuclear cells composed of macrophages, epithelioid cells and lymphocytes; these histological changes were associated with a bacterial dissemination limited to the superficial lymph nodes. A lymphoid hyperplasia with prominent germinal centers was observed in the draining lymph nodes from day 3 PI. These results illustrate the dual role of granulomatous lesions in chronic bacterial infections: although they limit bacterial dissemination, the granulomas do not impair the persistence of infectious organisms in the host, leading to focal tissue damage. PMID- 1746153 TI - Survival of Dermatophilus congolensis in tropical clay soils submitted to different water potentials. AB - The survival of a rifampicin-resistant mutant of Dermatophilus congolensis in vertisol and oxisol soils from Guadeloupe and in their constitutive clays was studied using a pneumatic device for controlling water potentials (pF). Experiments were carried out at two pF values simulating the wet season and the dry season. Survival time depended on the type of soil and its water content. Organic matter had a protective effect on the microorganism in oxisol but not in vertisol. The pathogenicity of D. congolensis was preserved in the soils which could therefore act as temporary reservoirs of this pathogen. Long-term survival of this organism in soils mixed with water suggests that ponds and dipping tanks may constitute sources of infection for cattle. PMID- 1746154 TI - Factors involved in immunity against Actinobacillus pleuropneumoniae in mice. AB - Active and passive immunization studies in mice were undertaken to examine the protective efficiency of vaccines prepared from different components of Actinobacillus pleuropneumoniae, or combinations thereof. Subcutaneous immunization using either washed formalinized whole cells, capsular polysaccharide, lipopolysaccharide or purified hemolysin I (105 kDa protein) partially protected mice against intranasal challenge with a lethal dose of homologous or heterologous A. pleuropneumoniae serotypes. However, full protection was obtained if the formalinized whole cells were supplemented with purified hemolysin. Similar protection was obtained when mice were immunized simultaneously with a sublethal dose of live cells by the intranasal route and with formalinized whole cells subcutaneously. Passive immunization using rabbit hyperimmune serum against formalinized whole cells provided almost total protection whereas hyperimmune serum against capsular polysaccharide, lipopolysaccharide or hemolysin alone provided only a partial protection. Cell mediated immunity as detected by the foot pad test may not be implicated significantly in the protein against acute A. pleuropneumoniae infection. However, humoral immune response seems to play an important role in protection. All the antigenic components examined may contribute to the protection to some extent. However, heat-labile components such as hemolysin and outer membrane proteins may play a crucial role in protection against acute challenge infection. PMID- 1746155 TI - Phenotypic variation in the outer membrane protein composition of Actinobacillus (Haemophilus) pleuropneumoniae: non-specific effect of exogenous pyridine nucleotide supply. AB - Actinobacillus pleuropneumoniae, grown in batch culture, was provided with pyridine nucleotides at concentrations that limited the final growth yield (pyridine nucleotide-deficient cultures) or did not determine the final extent of growth (pyridine nucleotide-sufficient cultures). Sarkosyl-extracted outer membranes from stationary phase, pyridine nucleotide-sufficient organisms contained 23,000 Mr and 43,000 Mr polypeptides that were absent (23,000 Mr) or barely detectable (43,000 Mr) in outer membranes from stationary phase, pyridine nucleotide-deficient organisms or exponential phase organisms. When growth ceased due to exhaustion of pyridine nucleotide, the ratio of the major outer membrane polypeptides (31,000, 38,000 and 69,000 Mr) was altered, becoming more like the ratio found with exponential phase organisms. Similar results were obtained when growth ceased due to glucose exhaustion at low biomass concentrations demonstrating that diverse nutrient deprivations can induce similar changes in outer membrane protein profile. All of these polypeptides were recognized by porcine immune sera indicating their production by A. pleuropneumoniae growing in vivo. PMID- 1746156 TI - Tetracycline resistance determinants in streptococcal species isolated from the bovine mammary gland. AB - Seventy-one streptococci isolated from dairy cows with clinical mastitis were tested for tetracycline resistance. Twenty-one (30%) isolates were tetracycline resistant (Tcr), and eight hybridized with the Tet O, one hybridized with the Tet L, and one hybridized with both the Tet L and Tet K determinants. The remaining Tcr isolates did not hybridize with any of the 5 Gram-positive Tet determinants tested. The Tet O determinants were plasmid-mediated, and four selected strains transferred the Tet O determinant at frequencies of 10(-6) to 10(-8). Strains which did not hybridize with known probes were tested for resistance to minocycline. All of the Streptococcus dysgalactiae had low minimum inhibitory concentrations (MICs) for minocycline, while the S. agalactiae and the one S. uberis showed high MICs to minocycline. This suggests that at least two different uncharacterized Tet determinants exist in these isolates, one conferring high resistance to both tetracycline and minocycline and one conferring only tetracycline resistance. PMID- 1746157 TI - Generation of aromatic-dependent Salmonella havana and evaluation of its immunogenic potential in mice and sheep. AB - The generation of aromatic-dependent (aro-) Salmonella havana (Group G2, 01, 13, 23) from a smooth wild-type parent strain by transduction with phage P1 is reported. Mice immunized with this live aro- S. havana strain (CS234) by the intraperitoneal (i.p.) route were protected against challenge with wild-type S. havana, whereas those immunized by the oral route were not. Mice immunized with two doses of formalin-killed aro- S. havana by the i.p. route were also unprotected, in spite of high antibody titers. However, only those mice immunized with live aro- S. havana by the i.p. route developed significant delayed-type hypersensitivity. Following i.p. inoculation in mice, the aro- S. havana strain CS234 was detected in the liver, spleen and mesenteric lymph nodes on day 9 but not on day 15 post-inoculation (p.i.). On the other hand, when mice were inoculated with the parent wild-type strain (CS4) or the aro- derivative strain CS234 by the oral route, the organisms were recovered from the mesenteric lymph nodes and intestine only on day 3 but not on day 6 post-inoculation. In sheep inoculated with the aro- strain CS234 in the gastroc muscle, organisms were recovered from the muscle, and popliteal and medial iliac lymph nodes for up to 21 but not 28 days p.i. However, no mutant organisms were recovered from liver, spleen, mesenteric lymph nodes or faeces. In orally-inoculated sheep, the mutant organisms were recovered from the mesenteric lymph nodes, rumen, intestinal contents, and faeces up to 14-21 days post-inoculation but not at 28 days. When sheep immunised with the aro- S. havana strain CS234 by the intramuscular or oral route were challenged with the parent wild-type S. havana strain CS4 by the oral route, the latter strain was detectable in the mesenteric lymph nodes and faeces of immune sheep up to 14 days post-challenge in contrast with the non-immune sheep, where the challenge strain was detectable even at 28 days post-challenge. Only sheep immunized by the intramuscular route developed high antibody levels and delayed-type hypersensitivity. PMID- 1746158 TI - Isolation of enterotoxigenic Escherichia coli from camels with diarrhoea. AB - E. coli serogroups 02, 08, 083, 0103 and 0120 were isolated from seven camels with diarrhoea of which 02, 08, and 083 were found to be enterotoxigenic on rabbit ligated ileal loop test. Out of 125 apparently healthy camels, 75 strains of E. coli were isolated. The majority of isolates were susceptible to gentamycin, nitrofurantoin, trimethoprim plus sulphonamide, neomycin, kanamycin and chloramphenicol. PMID- 1746159 TI - National Survey of Family Growth: design, estimation, and inference. AB - The purpose of this report is to document the procedures used in the 1988 National Survey of Family Growth (NSFG) to select the sample, weight the data to produce national estimates, impute missing data, and estimate sampling errors. Therefore, this report necessarily contains a great deal of technical detail. For readers who do not need this level of detail, this summary briefly describes the procedures used. The National Survey of Family Growth is conducted every few years by the National Center for Health Statistics (NCHS), a part of the U.S. Department of Health and Human Services. The purpose of the survey is to collect and publish data from a national sample of women on childbearing, factors affecting childbearing (such as contraception, sterilization, and infertility), and related aspects of maternal and infant health. Interviewing for Cycle IV of the survey was done in 1988 by Westat, Inc., under a contract with NCHS. Personal interviews were conducted between January and August of 1988 with a national sample of 8,450 women in the civilian noninstitutionalized population of the United States. Interviews were conducted in person by trained female interviewers and lasted an average of 70 minutes. The interview focused on the woman's pregnancies, if any; her use of contraception; her ability to bear children (fecundity and infertility); her use of medical services for family planning, infertility, and prenatal care; her marriage and cohabitation history, if any; and a wide range of demographic and economic characteristics. This report describes some of the main methodological aspects of the survey, including the sample design, weighting, sampling errors, and imputation of missing data. These topics will be described briefly and less technically in this summary. Each topic is discussed in more detail in the rest of the report. PMID- 1746160 TI - Incidence and impact of selected infectious diseases in childhood. AB - This report provides estimates of the lifetime and annual incidence of selected infectious diseases for children in various demographic groups. The social and health care impact of these diseases in terms of limitation in activity, bed days, school days lost, physician contacts, hospitalizations, surgery, and use of medication is also presented. The data are from the 1988 National Health Interview Survey on Child Health. PMID- 1746161 TI - Pantothenic acid in health and disease. AB - In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1746162 TI - Expression and function of the calcitonin gene products. PMID- 1746163 TI - Management of patients with sexually transmitted diseases. Report of a WHO Study Group. PMID- 1746164 TI - Control of Chagas disease. Report of a WHO Expert Committee. PMID- 1746165 TI - Evaluation of methods for the treatment of mental disorders. Report of a WHO Scientific Group on the Treatment of Psychiatric Disorders. PMID- 1746166 TI - [Malignant lymphoma of the spleen. Histological and immunohistochemical studies of morphology and differential diagnosis]. AB - 450 splenectomy specimens showing involvement by all save a few very infrequently occurring types of malignant lymphomas (ML) recognized by the updated Kiel classification of ML were investigated by conventional histologic and immunohistochemical methods. The results confirm and augment the findings of previous studies and facilitate a comparison of infiltration patterns of different ML in the spleen. These studies in conjunction with immunohistochemical detection of neoplastic cells may thus contribute to the diagnosis of minimal, i.e. early, splenic infiltration by ML and to the differential diagnosis of ML with advanced splenic involvement. Initially, most low grade NHL lead to nodular involvement of the splenic white pulp which may evolve into larger tumor nodules and/or diffuse red pulp involvement by invasion of adjacent red pulp structures. As a rule, the infiltrates are angiotropic, i.e. neoplastic cells accumulate in the vicinity of arterial and venous blood vessels both in the white and in the red pulp. Sinus involvement is frequently associated with leukemic generalisation of the neoplasm. High grade NHL are also localized predominantly in the splenic white pulp. However, their intrasplenic spread is characterized by the formation of large nodular and/or diffuse infiltrates which may efface the splenic architecture. Hodgkin lymphomas (HL), in contrast, cause coalescing tumor nodules which show expansive growth rather than progressive infiltration of the splenic parenchyma. These infiltration patterns of ML in the spleen are a constant finding. In conjunction with cytologic features and immunophenotype of the neoplastic cells they thus constitute reliable criteria for the differential diagnosis of ML in the spleen, although their anatomical and functional basis has not yet been fully elucidated. B and T cell lymphomas initially tend to show selective involvement of the original B and T cell areas of the spleen. Most high grade ML exhibit a similar behavior, although the size of the splenic lesions usually does not permit an exact identification of the ML's primary manifestation in the spleen. They thus exhibit a "homing phenomenon" to the two large lymphoid compartments of the spleen which is most conclusively illustrated by the "organoid" ML such as CB-CC or T zone lymphoma. This behavior has been interpreted to reflect the histogenesis of the neoplastic cells of the ML under study. In addition, specialised types of accessory cells such as CD35+ FDC and CD1/S100+ IDRC appear to be essential for the creation of conditions which are suitable for B and T lymphocytes, respectively. Progressive infiltration by neoplastic cells will lead to destruction of the normal microenvironment, i.e. alterations of FDC networks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1746167 TI - [Musculoskeletal manifestations in patients after bone marrow transplantation. Initial clinical rheumatologic observations]. AB - From January 1986 through January 1989 69 adult patients received bone marrow transplants--20 with autologous, and 49 with allogeneic bone marrow. Ten patients after autologous and 33 patients after allogeneic transplantation (TX) could be examined for rheumatological complaints. None of the patients after autologous TX displayed rheumatological manifestations; 8/33 patients after allogeneic TX developed bone necrosis and they had to be treated for several months with high daily doses of prednisolon (mean: 55 mg/day). In 18/33 patients an oligoarthropathy of large joints could be observed after a significant reduction of prednisolon dosage over a period of 5 months. In addition 15/18 of these patients later developed a chronic g-v-h-disease. The TX arthropathy may be induced by cortico-steroid therapy (resp. reduction), but most important, it is a clinical sign for an imminent chronic g-v-h-disease. PMID- 1746168 TI - Toxoplasmosis and systemic lupus erythematosus. Comparative serological studies. AB - There are still controversial views as to the relation between SLE and toxoplasmosis. Therefore, we looked for serological markers in both diseases. In patients with SLE (17), toxoplasmosis (28), and in normal controls (28) anti Toxoplasma gondii antibodies, anti-nuclear antibodies of different specificities, anti-histone and anti-cardiolipine antibodies, as well as antibodies against most common public idiotypes were measured. Significant increases in antinuclear antibodies and other SLE-related antigens were observed in patients with SLE. On the contrary, low levels of these antibodies were found in toxoplasmosis patients and in controls. The same was true for 16/6 anti-DNA idiotype antibodies. The incidence of anti-Toxoplasma antibodies in SLE sera did not differ in comparison with that in the normal population. Our data suggest that subacute and chronic toxoplasmosis do not play essential roles in generating the antibodies that are important to the pathogenetic mechanism operating in SLE. PMID- 1746169 TI - [Panhypogammaglobulinemia: a rare complication of parenteral gold therapy]. AB - Secondary antibody deficiency is one of the rare adverse effects of chrysotherapy in rheumatoid arthritis. The plasma levels of all immunoglobulins fall into ranges significantly lower than the tolerable physiological minimum. The long lasting panhypogammaglobulinemia can increase the risk of infection in the patient and, therefore, should be closely monitored. Hence, a record of immunoglobulin levels before and during therapy with gold compounds seems to be mandatory. PMID- 1746170 TI - [The medical computer as a diagnostic aid in joint pain--attitude of patients and results]. AB - 409 unselected outpatients were asked standardized expert system questions on the medical history of joint complaints. An average number of 30.4 +/- 6.6 out of 60 questions with 346 different answers were asked in a mean time of 20.1 +/- 6.6 min. This time, required for the questions to be displayed on the computer screen and input assistance from a staff-member, proved to be comparable to the time required for a medical history to be taken on the same patients by a physician. In 75% of the cases the computer was able to predict the correct diagnosis on behalf of information of the medical history only. Using only medical history as a source of information, computer and physician had the same rate of wrong diagnoses. Before and after the standardized medical history on the computer screen all patients were asked about their opinion of the computer as a diagnostic aid. Male and younger patients more often appreciated computerized diagnosing. Just a few patients felt that their relation to the physician was disturbed by the computer or were inconvenienced themselves. Most patients stated they did not believe that physicians could ever be replaced by computers. Only a few of them had resignations about storage and statistical utilization of personal data. PMID- 1746171 TI - [Arthritis in lambliasis intestinalis (giardiasis) in the adult]. AB - Joint involvement in giardiasis is reported in children and young persons only with one exception. We present two cases of adult patients (a thirty-year-old woman, 26-year-old man) who developed a slowly aggravating arthritis in PIP joints, ankles and knees with a tendency to chronification or relapse. Giardiasis was diagnosed by examination of feces. Treatment with ornidazole was effective in arthritic and gastrointestinaly symptoms. The patients had neither ESR elevation nor any other signs of inflammatory processes. The arthritis factor was negative. HLA-typing showed no phenotypes associated with arthritides. PMID- 1746172 TI - [Fungus-induced arthritis caused by Scedosporium apiospermum (Pseudallescheria Boydii)]. AB - Scedosporium (monosporium) apiospermum is the most common causative agent of maduro mycosis. Recent research reports claim that this fungus can also induce arthritis. We report on the disease in a woman from a rural area who was admitted to our clinic because of arthritis symptoms. We were able to detect Scedosporium apiospermum, i.e., it was probably a fungus-induced arthritis which had developed after an intraarticular steroid injection. PMID- 1746174 TI - Dosage of alpha tocopherol in osteoarthritis. PMID- 1746173 TI - [Progressive multifocal leukoencephalopathy as a cause of neurologic symptoms in Sharp syndrome]. AB - Progressive multifocal leukencephalopathy (PML) is a very rare complication of immunosuppressive or cytostatic treatment of rheumatic diseases. We describe a patient with a mixed connective tissue disease (MCTD) existing for more than 15 years, who had polyarthritis, myositis, scleroderma-like symptoms, pulmonary involvement, and psychosis of undetermined origin. After a 12-year low-dose corticosteroid therapy and a 4-year azathioprin therapy a quickly progressive PML developed; symptoms included: difficulty in urinating, bladder, articulation, spastic hemiplegia, eye movement malfunction. The patient died after after a few months. PML is an important consideration in the differential diagnosis when a patient with MCTD develops neurologic symptoms. PMID- 1746175 TI - [Peritoneal lavage in the diagnosis of blunt injuries of hollow intra-abdominal organs]. AB - In some cases of blunt abdominal trauma lesions of gastrointestinal tract are occasionally found. The difficulty with these injuries lies in establishing the diagnosis. Clinical examination alone does not reliable evidence, particularly if the patient is unconscious and therefore unable to respond subjectively. Although abdominal sonography ist becoming increasingly important in the diagnosis of blunt abdominal trauma lesions of the gastrointestinal tract frequently remain undetected or are diagnosed to late where this method of examination is used exclusively. In the retrospective analysis of our patients we have encountered serious complications such as peritonitis and even cases resulting in death. On the other hand when peritoneal lavage was employed, no false negative results occurred. Consequently the value of this method in the diagnosis of blunt abdominal trauma and possible lesions of the gastrointestinal tract is indisputable. PMID- 1746176 TI - [Analysis of the frequency of blood transfusion in surgery]. AB - For the period from 1985 to 1987 were analysed the blood transfusions, which were carried out in seven surgical wards, within the scope of a study for quality assurance. 7.6% of the patients, treated in surgical ward and 5.4% of the patients, treated in traumatological ward, were given blood transfusion. The average was 3.6 transfusional units per treated patient. The biggest differences were to be remarked at cases of breast cancer and at thyroid gland surgery. The average transfusion frequency at breast cancer was 16% with a difference between 5 and 63%. In thyroid gland surgery the average transfusion frequency was 11%, differing between 1 and 54%. At these operation groups the blood transfusion were usually given once. Transfusional reactions, costs and responsibility towards the donor demand a turning away from scientifically non-established transfusion habits. The components concept by Lundsgaard should serve as an orientation. PMID- 1746177 TI - [Fibronectin content in wound secretions as a criterion of the course of wound healing]. AB - The content of soluble immunoreactive fibronectin in wound exudate in 104 patients after appendectomy, laparotomy and thermal injuries was studied both in non-complicated and purulent postoperative wounds. It was shown that in the case of non-complicated wound healing fibronectin reached maximum level at the 2nd and 3rd postoperative days. At the following days the fibronectin content decreased and returned at the 4th-5th days to the first day level. In the purulent wound the amount of fibronectin in the exudate remains low in the hydratation phase rising significantly in the phase of dehydration. The described changes correlate well with the clinical signs of wound healing. The data suggest that the fibronectin content in wound exudate can be used in evaluation of wound healing, prediction of possible complications as well as in control of treatment efficiency. PMID- 1746178 TI - [Our surgical heritage. Ambroise Pare (1510-20 December 1590). His life and work]. PMID- 1746179 TI - [Diverticular disease. Pathology and clinical aspects based on 368 autopsy cases]. AB - There were found 368 cases (4.5 percent) of diverticulosis of the intestine based on 8124 autopsies in the years of 1979 till 1988 with regard to their localisation, complications and accompanied diseases. In 174 of 368 cases clinical files could be examined and integrated in the evaluation. Sigmoid diverticula were most frequently followed from duodenal diverticula chiefly in the immediate vicinity of the "Papilla of Vateri". Constipation, stomachache, haemorrhoids and spasm of the anal sphincter were typical complaints. One during lifetime known diverticulosis was noted only approximately half on the autopsy application as a second disease. The autopsy results a complication of diverticula (mostly with a peritonitis) in 39 percent as the primary cause of death. Most frequently complication was a diverticulitis (in 16.8 percent refer to the total number). Arteriosclerosis, hypertension and/or diabetes (so called "civilization diseases") were in the main accompanied diseases, which were found too. Surgical intervention took place principal under suspicion of malignoma or as an "acute abdomen". Non-characteristic complaints (protraction by the physician) and the ignorance of the illness among the population (protraction by the patients) are disadvantageous to the identification of the diverticulosis. Because the diverticulosis as a disease of the economic developed countries represents a growing problem ought to direct more attention to prevention, which consists in application of food rich in ballast-substances and the treatment of the constipation. PMID- 1746180 TI - [Surgical therapy of complicated diverticular disease]. AB - From 1975-1989 55 patients were operated on for complicated diverticular disease at our unit. Intraoperative we found the following complications: 21 walled of perforations, 22 stenosis of the sigmoid colon combined with obstruction of the small and/or large bowel, 8 free perforations with generalized, faecal peritonitis, 7 diverticular fistulae (5 colovesical, 1 colojejunal and 1 colocutaneous fistula) and diverticular bleedings. In 33 cases we performed a resection with primary anastomosis (8 times with protecting stoma). 17 times the Hartmann's procedure was carried out and 5 times a transverse colostomy and drainage was elected. Lethality was 20% and morbidity came to 25%. We consider the primary resection with primary anastomosis to be the procedure of choice for complicated diverticulitis except for free perforation with generalized and faecal peritonitis where we prefer the Hartmann's procedure. PMID- 1746181 TI - [Is prevention of pre-eclampsia possible?]. PMID- 1746182 TI - [Polycystic ovary syndrome: central or peripheral disorder of regulation?]. AB - Survey about the reasons of PCO-syndrome. Possible are central or peripheral disturbances of regulation, but the reason is not known because of multifactorial disease. Therefore there is no causal treatment, too. PMID- 1746183 TI - [Induced abortion--a critical life change event]. AB - In the present survey the psychic and physical mastering of abortion is considered to be a subject of the research of a "critical life-event". Special interest was devoted to the consequences of the process of mastering before and after abortion on the mental and physical condition of the examined human females (n = 39). The diagnosis showed that especially before abortion in a time of a serious state of inner conflict, interference concerning the physical condition and psyche of women arise, while actually after abortion the mood is more euphoric. The inconvenience increased in dependence on experience of social welfare and support. Three months after abortion specific complaints such as pains in the lower abdomen, bleeding and sudden urge to cry occur. The administration of contraception after abortion is becoming significantly safer. PMID- 1746184 TI - [Preoperatively as adnexa tumor diagnosed mucocele of the appendix]. AB - In a 51 year old woman a cystic in the right lower abdomen was diagnosed by ultrasound. The patient underwent laparotomy assuming the tumor to be a right adnexal mass. Intraoperatively, a pathological appendix was found. Histologic evaluation of the appendix showed a mucinous cystadenoma with mucocele. PMID- 1746185 TI - [Hygroma colli--sonographic indication of fetal chromosome abnormality. A case report]. AB - Transvaginal sonography has been developed as an useful tool to recognize and define structural defects in the first trimester fetus. Fetal cystic hygromas as an manifestation of malformation of the lymphatic system are often the only sign of an severe fetal anomaly. In 70-80% of cases cystic hygroma is associated with a Turner-Syndrome (45,XO). We report a case in which transvaginal sonography has been the only instrumental in the prenatal diagnosis of a nuchal cystic hygroma. Based on this sonographic finding the pregnancy has been terminated. We point to the value of early and subtle ultrasound examination as an excellent method in finding hints for chromosome abnormalities. PMID- 1746186 TI - [Defense mechanisms exemplified by repressed pregnancy]. AB - Case report on a repressed pregnancy in a 19 year old women. Her short biography is demonstrated. For explaining this phenomenon theoretical models of defense behaviour from the perspective of psychoanalysis and information psychology had been described. These considerations are discussed connected with the case report. PMID- 1746187 TI - [Learning at the bedside of pregnant patients. On the typology of the birthing center in Germany (1728-1840)]. AB - The process of institutionalization of obstetrics in the German universities is investigated on the basis of contemporary accounts and archival documents. The inauguration of the "school for midwives" by Johann Jakob Fried at Strasbourg (1728) was followed after 1750 by the foundation of numerous other obstetric departments and lying-in hospitals, in which midwives and medical students could attend a regular and systematic bedside-teaching for the first time. As to the architectural types, four basic structures have to be distinguished: Whereas in big cities the teaching centres were integrated in pre-existing hospitals (type A), the setting up of lying-in hospitals in regional universities took place in decaying old buildings (type B). The organizing of an obstetric ward in the former "clinicum" together with the medical and surgical department (type C) was rather seldom. Before 1850 the construction of expensive new buildings for lying in hospitals (type D) was only realized at few places. In conclusion the emphasis is put on the political intentions and tendencies of the enlightenment philosophy which influenced considerably the creation and the development of the first teaching centres for obstetrics. PMID- 1746188 TI - [Frankfurt Toxoplasmosis Symposium. 14 June 1990 in Frankfurt (Oder)]. PMID- 1746189 TI - [IV. Symposium on Anlage and Disorders of the Differentiation of Genital Organs 31 August-1 September 1990 in Greifswald]. PMID- 1746190 TI - [CIN--what influence do smoking and socioeconomic factors have?]. PMID- 1746191 TI - [10th Congress of the Urogynecology Section 11-13 October 1990 in Greifswald and Sellin/Rugen]. PMID- 1746192 TI - [25th National Congress of Obstetrics and Gynecology of the Democratic Republic of Korea 1-3 August 1990 in Pyongyang]. PMID- 1746193 TI - [Pregnancy following organ transplantation]. AB - Pregnancies following organ transplantation are high-risk pregnancies for mother and fetus. There are many reports concerning pregnancies following renal transplantation whereas only few reports are published about pregnancies in recipients of liver, heart and bone marrow transplants. During the pregnancy after kidney transplantation pregnancy-induced hypertension can develop or the renal function can decrease. Risks for the fetus are prematurity, growth retardation and prenatal infections. A higher incidence of complications for mother and fetus is observed in patients with renal insufficiency or severe hypertension prior to conception. The risks can be reduced by an intradisciplinary cooperation of gynecologist, transplant specialist and paediatrician. The paediatrician. The experiences with pregnancies in women after organ transplantations in the Medical School of Hannover are analyzed and compared with the reports in the literature. The management of these patients is described on current state of knowledge. PMID- 1746194 TI - [Degree of DNA ploidy and steroid hormone receptors as prognostic factors in endometrial carcinoma]. AB - In a prospective investigation the concentration of DNA (ploidy) and of steroid hormone receptors (ER and PgR, resp.) were studied in endometrial carcinoma and related to each other, to established morphological prognostic criteria (stage, typing, grading, relative invasion of myometrium), and to the clinical progress of disease, respectively. The microscopic spectrophotometric analysis of DNA showed diploid main lines in 2/3 of investigated endometrial carcinoma. It could be demonstrated a relationship between heteroploidy, decreased mean concentrations of ER and PgR, unfavourable prognostic factors (stage II-IV, G3, myometrial invasion of greater than 2/3) and clinical progress of disease. The mean value of ER and PgR was higher in diploid carcinoma than in heteroploid ones. Significant differences were found both in the relation of the PgR concentration to different tumor stages (stage I vs. II-IV) and of the concentration to the different types of ploidy. Exceeding the histological differentiation, the determination of DNA and ER/PgR receptors can results in additional prognostic informations for a scientific proved, adjuvant or curative strategy of therapy after the operation. PMID- 1746195 TI - [The menopause--a sociopsychological interpretation]. AB - The psychological situation of climacteric women is determined by social economic and cultural changes. The educational backgrounds and family life are factors to a high degree of life stress, too. Psychosocial analysis and more informations about the conflicts in this time are preconditions for a successful treatment of menopausal complaints before hormone replacement in the gynecological praxis. PMID- 1746196 TI - [Plasma level and metabolism of vitamin A (Vitadral) in women of reproductive age]. AB - Using a sensitive HPLC method, plasma concentrations of vitamin A and metabolites were measured from 6 female volunteers who had taken once daily 0.46 mg/kg BW retinol palmitate (Vitadral) for 10 days. The metabolites all-trans- and 13-cis retinoic acid were increased significantly (2- and 5-fold, resp.) 6 h after the ist intake. 13-cis-4-oxo retinoic acid the 10th intake in the morning of the 10th day (9.22 +/- 2.77 ng/ml, 4-fold increase). The results show continuous increase of retinoic acids, which have to be considered as potential teratogens, after administration of vitamin A. The plasma concentration of retinol itself did not change, whereas only short-term increases were observed for retinol esters. PMID- 1746197 TI - [Micturition and incidence of postoperative urinary tract infections in surgical gynecology]. AB - In a retrospective analysis postoperative courses of 879 patients (1987-1989) have been analysed with respect to micturition behaviour and incidence of postoperative urinary tract infections. 58.5 per cent urinary tracts infections could be registered following uro-gynecology operations and 48.9 per cent after radical hysterectomies according to Wertheim-Held. The lowest rate of 15.9 per cent we found after simple interventions at the adnexas. Within the uro gynecological operations vaginal plastic procedures had a higher rate (66.4 per cent) than colposuspensions with 41.5 per cent. Because of the different extent of the bladder preparation there were distinct differences with regard to first spontaneous micturition and lack of residual urine. PMID- 1746198 TI - [Sonographic diagnosis of fetal lung maturity--a new method]. AB - First results are presented to determine the maturity of fetal lung by sonography. Using the fetal liver as a reference-organ we are avoiding the known pitfalls which made it impossible in the past to standardize the fetal lung changes depending on the age of gestation. We examined 104 patients between week 27 and week 41. In one ultrasound section cut we depicted as well lung and liver. According to the known A-mode we registered frequencies in both organs. The registered frequencies were entered digitally into a computer and checked for f mean, f max and f min. Afterwards the frequencies of the lung were divided by those of the liver. Of all weeks of gestation the mean value and standard deviation were calculated. We found the liver as an adequate reference-organ, since there is no change of the reflection pattern between the different weeks of gestation, while there are significant changes to be registered in the fetal lung, a cutting line being week 35. A quotient of f mean lower than 1.1 hints to lung maturity while values over 1.1 point to immaturity. This was confirmed by several cases of analysis of amniotic fluid (L/S-ratio). Further comparisons with amniotic fluid results will have to validate these findings. PMID- 1746199 TI - [Multiple coagulation disorders following cesarean section]. AB - We refer to a case report describing the diagnostic and therapeutic problems resulting in multiple intra- and postoperative coagulation disorders. Differential diagnostic indications respecting to the most important disorders within the coagulation system are described especially. Local hyperfibrinolysis is accounted in detail; besides we inform about our own therapeutic experiences. PMID- 1746200 TI - [Coexistence of endometroid carcinoma of the ovary and endometrial carcinoma in a 32-year-old woman]. AB - At our hospital a 32 year old patient with a cystic ovarian had been operated. Because sonography was without pathological findings and the patient showed a sterility type, laparoscopy was indicated. Histological findings showed invasive growth of a tubulopapillary carcinoma. Laparotomy with hysterectomy, bilateral adnexa removal, omentectomy as well as pelvic and para-aortic lymphadenectomy was examined. Histologic and immunohistochemical investigations led to coexistence of ovarian endometroid carcinoma and to an endometrial carcinoma, both tumors being of different antigenicity. PMID- 1746201 TI - Human cervical mucus: its enzymes. PMID- 1746202 TI - Monitoring ovulation by ultrasound and hormonal parameters. PMID- 1746203 TI - Antispermatozoon antibodies and cervical factor of sterility. PMID- 1746204 TI - Simultaneous dosage of oestrone-3-glycuronide and pregnanediol-3-glycuronide in urines to monitor the fertile period in the woman. PMID- 1746205 TI - The simplicity of the Ovulation Method and its application in various circumstances. PMID- 1746206 TI - The canalization of cervical mucus in the human fertility. PMID- 1746207 TI - Changes in fatty acids sebum composition during human menstrual cycle: possible relationships with fertile period. PMID- 1746208 TI - Natural contraceptive methods. PMID- 1746209 TI - The anatomical bases of human fertility. PMID- 1746210 TI - The validation of the Billings ovulation method by laboratory research and field trials. PMID- 1746211 TI - Human leukocyte antigen compatibility and failure to achieve a viable pregnancy with assisted reproductive technology. AB - Many couples fail to achieve a viable pregnancy with multiple attempts of Assisted Reproductive Technology (ART). Immunologic rejection of the embryo may be a factor in these couples. We evaluated shared human leukocyte antigen (HLA) antigenicity in 10 couples who failed multiple ART cycles and compared them with 10 couples who achieved a viable pregnancy with their first ART attempt. Study couples shared a statistically significant greater number of HLA antigens than control couples. Leukocyte immunotherapy is discussed. We conclude that couples who share multiple HLA antigens may have an immunologic basis for failing to achieve a viable pregnancy with multiple ART cycles. PMID- 1746212 TI - Computer assisted sperm motility analysis. AB - The CellSoft system was employed to study its reliability in the evaluation of seminal data in fertile and infertile subjects. In addition new motility data were introduced and added to the classic parameters. Various clinical and experimental applications are reported. The system is valid and extremely useful in seminal research. In order to obtain the above mentioned benefits it is necessary for the users to have extensive experience of seminology and computer technology. PMID- 1746213 TI - Pericentric inversion of chromosome 5: a possible threat to male fertility? AB - Pericentric inversion of chromosome 5 (inv(5)(p12,q13] was diagnosed in two unrelated men with normal phenotype referred for infertility. The spermatogenic damage in these patients may be explained on the basis of the X-Y bivalent behaviour in cases of some balanced structural rearrangements of the chromosomes. The Authors propose a possible negative action of inv(5) in male gamete production and suggest a larger use of the chromosome analysis in the study of male infertility. PMID- 1746214 TI - Antibodies to spermatozoa. XII. The critical performance of the Gelatin Agglutination Test (GAT). AB - The Gelatin Agglutination Test for detection of sperm antibodies was critically studied and evaluated. This fundamental technique for the detection of sperm antibodies was now modified in a number of details. The new procedure, termed GAT II, is more convenient, economical, and reliable than the older form of this procedure; the volumes used are half as much, thus using less serum and less antigen, the mixtures are prepared within each Kibrick tube, thus requiring fewer transfer steps, and the foam problem is prevented, thus making observation more accurate. Secondly, an extensive study was made of the effect of the time of incubation in this procedure, comparing 30, 60, and 120 minutes for each test mixture. It was found that only 7 of the 50 tested sera (14%) showed a positive result at 30 minutes, although all 50 were positive at 120 minutes. Various details of this sort must be carefully considered, in order to make this test fulfill its potential and have maximum reliability for clinical significance. PMID- 1746215 TI - Artificial insemination for oligospermia. A critical review. AB - The study concerns the review of the literature concerning the effectiveness of artificial insemination in cases of oligospermia. Differences in AIH techniques, the lack of standardized methodology explain the wide range of discrepancies in the resulting pregnancy rates. Still, in the course of time, a few certainties have been acquires: A detailed and thorough investigation of the female partner is mandatory. The use of fresh ejaculates is today totally obsolete, even with the help of cups, intra-cervical or eventual intra-uterine insemination. The standardization of seminal parameters still remains an unsolved problem. At the present time, intrauterine insemination with capacitated sperm is the method of choice. Still a basic condition is mandatory: a minimum of 1 M motile capacitated spermatozoa is required. Timing of insemination determined by the LH peak seems the most valuable procedure. The overall benefit is low, +/- 5% conception rate per cycle, and short lived because of the strain involved in an optimalized procedure. The policy to plan 3 to 6 AIH cycles before going over to an IVF procedure is the more debatable. PMID- 1746216 TI - The use of the Salt Stored Zona Assay in the study of the sperm function: methodological approach. AB - The authors mention many tests to study sperm function. On their opinion, the best model to evaluate spermo-oocyte interaction is the in vitro fertilization but it cannot be considered a test for ethical and practical problems. To overcome these problems they propose the Salt Stored Zona Assay to evaluate the spermatozoa. PMID- 1746217 TI - Echoguided transvaginal oocyte retrieval: effective and easy to learn technique. AB - Echoguided transvaginal oocyte retrieval gives good results even when carried out after a short training course. This study compares the results obtained by a group of physicians with long experience and a newly-trained group. No significant differences were found in the percentages of follicles punctured (87.9% vs 91.9%), of oocytes recovered (62.8 vs 70.6%), in the mean number of follicles aspirated (4.5 vs 4.1) or in duration of the procedure (33.9 min vs 34.2 min). No complications occurred in the retrieval and the patients, pain was very slight. PMID- 1746218 TI - Medical treatment of ectopic pregnancy. AB - Methotrexate is an alternative to surgical treatment of unruptured tubal pregnancy. Among 39 women with the diagnosis of tubal pregnancy there were ten10 cases without rupture of salpinx. Nine9 out of these treated with Methotrexate. In one1 case there was rupture immediately after the termination of the treatment. There were no experiences of major side effects from the treatment with Methotrexate. The passage through the tubes was examined laparoscopically 3 months after the treatment. There was passage through all affected tubes. PMID- 1746219 TI - Vertebral artery tortuosity with concomitant erosion of the foramen of the transverse process of the axis. Possible clinical implications. AB - Thirty-six vertebral arteries were examined for the presence of tortuosity in their trajectory through the neck. Of these, 18 vessels (14 bilateral) showed various degrees of tortuosity of their proximal segment. Four arteries had marked kinking of the tortuous vessel at the foramina of the transverse process of the axis. These foramina presented with marked erosion of the underlying bone. Four other axes presented with moderate erosion of the F/Tp. The etiology and clinical significance of tortuosity of the vertebral artery, and erosion of the F/Tp of the axes, are discussed in light of the extreme range of rotation occurring at the C1-C2 segmental level. PMID- 1746220 TI - Subepithelial elastic system fibers of oblique mucosal folds in the rat proximal colon. AB - The proximal colon of the rat is characterized by a 'herring bone' pattern of oblique mucosal folds (OMF) which are arranged in a parallel array. By light and electron microscopy the OMF exhibited rich subepithelial elastic system fibers which bound the epithelial basement membrane and the smooth muscle cells of the lamina propria together. The elastic system fibers usually consist of elastic, elaunin and oxytalan fibers. However, the subepithelial elastic system fibers of the OMF were composed of relatively thin elastic fibers with a few microfibrils, and elaunin and oxytalan fibers which were almost indiscernible. Areas other than the OMF were quite poor in subepithelial elastic system fibers. The interpositions between each of the OMF were composed of typical components: elastic, elaunin and oxytalan fibers. The composition of the subepithelial elastic system fibers of the OMF does not correspond to that of any other organs previously reported. The present study suggests that the OMF of the rat proximal colon might be equipped in such a way to resist to distension or compression. PMID- 1746221 TI - Are Ranvier's nodes artifacts by preparation? AB - To avoid artifacts, native nerve fibers were investigated by phase contrast light microscopy. It was shown that Ranvier's nodes cannot be seen. At the sites at which they can be produced by thermal and chemical effects, a tight joint of the tube ends of the 'internodes' inverted to the inside are to be found. Some structures of Ranvier's nodes do not exist in intact living nerves. This fact can also be proved by electron micrography. PMID- 1746222 TI - Ramification pattern of intermetacarpal branches of the deep branch (ramus profundus) of the ulnar nerve in the human hand. AB - The branching pattern of the deep branch (ramus profundus) of the ulnar nerve and its relation with the target were analyzed in the human hand by an improved dissection method. After sending off branches to the hypothenar muscles, the r. profundus branched off an ulnar stem and a radial stem to the fourth, to the third and to the second intermetacarpal spaces, respectively, in this order, and an ulnar stem to the first to become terminal branches. The ulnar stems included an ulnar interosseous branch and a superficial articular branch in addition to a lumbrical branch in the third and fourth intermetacarpal spaces. The radial stems included only a radial interosseous branch. The branching pattern of the ulnar stems as well as its topographical relationship with the radial stems indicated a fundamental spatial arrangement of the branches in the intermetacarpal spaces: the lumbrical, superficial articular, ulnar interosseous and radial interosseous branches were arranged fundamentally in this order from ulnar to radial in each space; the first three branches may form a common trunk. The present observations demonstrate that individual nerves in the extremities may have a regular branching pattern, contrary to most of the previous observations. PMID- 1746223 TI - Ultrastructure of the red pulp in spleen innervation in horse and pig. AB - The innervation of the red pulp in the spleen of horse and pig was investigated by electron microscopy. In addition, the neurilemma was studied by immunohistochemistry specific for S-100 protein. In the pig, a large population of smooth-muscle cells extending from the smooth-muscle trabeculae was present in the red pulp. The cytoplasmic processes of reticular cells enwrapped the smooth muscle cells, and nerve fibres were distributed between the smooth-muscle cells and the reticular cells. The nerve terminals clustered toward the facing of the smooth-muscle cells. Nerve fibres and terminals were not disclosed within the sheathed artery. Immunohistochemically the neurilemma showed a reaction positive for S-100 protein. In the horse, no smooth-muscle cells were noted in the red pulp. The nerve fibres terminated around the cytoplasmic processes of the reticular cells. Nerve fibres and terminals were disclosed within the sheathed artery, and the terminals contained both large and small dense-cored vesicles. Immunohistochemically the neurilemma showed a reaction negative for S-100 protein. These findings support the presence of the axon-bearing reticular cells described earlier in the horse spleen. PMID- 1746224 TI - Left superior vena cava with atrial displacement. AB - Two cadavers were dissected showing persistence of left-sided superior vena cava with atrial displacement and inversion of the venous drainage from the body wall (azygos system of veins). The presence of atrial displacement in relation to a persistent left superior vena cava observed in this study lends support to the view that haemodynamic factors influence the morphogenesis and development of the heart. The development of an asymmetrical venous pattern from a symmetrical venous drainage may be influenced by the same factors which influence the arterial end of the primitive heart tube. PMID- 1746225 TI - Experimental study of the origin of the parathyroid glands. AB - The origin of the parathyroid glands was investigated in chick embryos (Gallus domesticus). Pieces of the third branchial arch were grafted, and its ectodermal layer formed a new structure (parathyroid III), which became separated from the placodial ectoderm. This structure continued to develop until, together with neural crest cells which gave rise to the mesenchyme, it formed a distinct parathyroid III gland by stage 28 of Hamburger and Hamilton. PMID- 1746226 TI - Changes in prolactin cells caused by partial hepatectomy in the rat. AB - In order to study ultrastructure alterations in prolactin (PRL)-secreting cells, PRL cells of the anterior pituitary glands of partially hepatectomized female rats were observed by the protein A-gold procedure with the electron microscope. Simultaneously, their serum PRL and estradiol (E2) levels were measured by radioimmunoassay. After about 70% hepatectomy PRL cells were remarkably changed, that is active granule extrusion, prominent Golgi vesicles and a hypertrophic rough endoplasmic reticulum were observed. These changes were most remarkable on day 3 after the operation. Significant increases in serum PRL and E2 were also seen following partial hepatectomy. It may be assumed that the morphological changes in PRL cells and the elevation of serum PRL were probably due to surgical stress and to the diminution of E2 receptors in the liver after partial hepatectomy in the rat. PMID- 1746227 TI - Tibial dimensions before and during the recovery phase in the osteopetrotic mutant mouse. AB - Osteopetrosis is a genetic bone disease characterized by excessive bone mass and 'clubbing' of long bones. In the osteopetrotic (op) mouse, remission of the disease begins at 45 days of age. This study attempted to describe changes in the op tibia before and during remission. Osteopetrotic and normal littermates were killed at intervals from 10 to 120 days of age. Left tibiae were processed for transmission electron microscopy. Microradiographs of right tibiae were projected and drawn. Bone dimensions were compared between mutants and controls by ANOVA and bones were viewed in a scanning electron microscope. Differences between mutants and controls were: at all ages mutant tibiae were shorter than those of controls; 10-day distal shafts of mutant tibiae were significantly narrower; 30 day proximal shafts of mutant tibiae were wider, distal shafts were narrower, and there was no bone resorption along the external proximal metaphysis. At 48 days, resorption was seen along the proximal metaphyses of the mutant tibiae and by 60 days, extensive resorption areas were evident. However, proximal shafts of mutant tibiae were still significantly wider than those of controls. These results indicated that before remission there was an unequal deposition of bone on the mutant tibia. After remission, resorption occurred along the external proximal shaft, but was not enough to remove significant amounts of bone from the proximal metaphyses of mutant tibiae by 120 days of age. PMID- 1746228 TI - Is exencephaly the forerunner of anencephaly? An experimental study on the effect of prolonged gestation on the exencephaly induced after neural tube closure in the rat. AB - Exencephaly is said to precede anencephaly resulting from failure of the rostral neuropore closure. In order to verify if the exencephaly induced after neural tube closure would also lead to anencephaly, exencephaly was induced in rat fetuses by maternal administration of a single dose (15 mg/kg) of cyclophosphamide on day 12 of gestation and pregnancy was prolonged by uterine ligation until postconception (PC) day 24. Fetal death was found to increase with prolongation of gestation and no sign of recovery from growth retardation was observed. Alizarin red-S-stained skeletal preparations substantiated the persistence of skull malformations in the exencephalic fetuses. Histological observations of the mesenchyme and the brain indicated degenerative changes that were intensifying with time. The ventricular system expanded progressively; the ependyma was denuded and neural mass lay free in the ventricle. The choroid plexus appeared to be elaborate and extensive. The haemorrhagic capillary network around the brain tissue was highly proliferative and appeared to penetrate the former from the exterior. Tissue necrosis seemed to progress unabated. Cystic spaces appeared beneath the base of the brain and became progressively large and it appeared as if the brain was being pushed out of the shallow cranial fossae. By PC day 24, most of the brain tissue had degenerated, thus giving clearly the appearance of the anencephalic condition. PMID- 1746229 TI - Morphological studies of the foramen caecum linguae of the human and guinea pig tongue. AB - A three-dimensional study of the development of the thyroid gland in human and guinea pig embryos was made together with a histological investigation of the foramen caecum of the human adult tongue. In the human embryo, an epithelial depression was not seen between the first and second branchial arches except a shallow sulcus. Ciliated cells were observed on the dorsal surface of the tongue in all embryos which exceeded 18 mm in crown-rump length. The presence of a foramen caecum was observed in 18 (51%) cadavers from 35 human adults. Several circumvallate papillae were found in a 10-mm-deep foramen caecum on the side adjacent to the anterior two thirds of the tongue. In all specimens serous glands open into the foramen caecum. PMID- 1746230 TI - Expression of plasma membrane alkaline phosphatase in normal and regenerating choriocapillaris in the rabbit. AB - Ultrastructural histochemistry for plasma membrane nonspecific alkaline phosphatase was performed on the normal and regenerating choriocapillaris (CC) of rabbits. In normal animals the CC endothelium expressed little or no staining, whereas in regenerating CC the endothelium exhibited staining. The staining was most intense at the unfenestrated plasma membrane. As the capillaries matured and the fenestrated plasma membrane became more extensive, the staining was reduced and eventually eliminated. Pericytes did not stain in normal or regenerating CC. PMID- 1746231 TI - Anatomical basis for the clinical application of the arterial supply of musculus pectoralis major. AB - The pattern of arterial supply to the various parts (clavicular, sternocostal and aponeurotic) of the pectoralis major muscle was studied in 7 cadaver dissections and 10 angiograms by injecting a radio-opaque substance. Three main arteries supplied the muscle, i.e. the pectoral branch of the thoracoacromial trunk (TAT PB), the lateral thoracic artery and the perorating branch of the internal thoracic artery, supported by other branches of the TAT and the superior thoracic artery. It is observed that the TAT-PB, a chief vascular pedicle, anastomoses freely with other arteries and supplies most parts of the muscle. The present study is mainly focussed on the exclusion of the chief vascular pedicle of muscle to eliminate the confusion of previous studies and prevent the unnecessary hindrance and complications of the muscle flap. PMID- 1746232 TI - Immunohistochemical localization of basic fibroblast growth factor in ependymal cells of the rat lateral and third ventricles. AB - The presence of basic fibroblast growth factor (bFGF) in the third and the lateral ventricular ependyma of the rat has been investigated under the light microscope using a polyclonal antibody against bFGF, through the unlabelled peroxidase-antiperoxidase procedure; bFGF-immunoreactivity (bFGF-IR) is observed in the entire ependymal cell layer of ventricles. Also ependymal tanycytes within the inferior portion of the wall and floor of the third ventricle show bFGF-IR. Tanycytic processes are in close contact with hypothalamic capillaries. The present study strongly suggests that brain ependymal bFGF plays unidentified roles unrelated to its angiogenic or mitogenic capacities. PMID- 1746233 TI - Characterization of the cytoskeleton in human normal and otosclerotic osteoblast like cells. AB - The localization and distribution of some cytoskeletal protein components were studied by immunostaining methods in normal and ostosclerotic osteoblast-like cells. The protein components investigated were microtubules (beta-tubulin), intermediate filaments (vimentin), microfilaments (actin and myosin) and structural proteins (alpha-actinin and fibronectin). Although the mechanism is not yet clear, the alterations observed in the pathological cells could well play a role in the expression of otosclerosis. PMID- 1746234 TI - Morphometric analysis of compartments concerned with secretion of parathyroid hormone in male and female rats. AB - Parathyroid cells responded to estradiol application in rats by increment in surface area of the compartments concerned with parathyroid hormone secretion, i.e. the rough endoplasmic reticulum, Golgi complex and secretory granules. We thus compared the morphology of parathyroids of male rats with those of females of the same age and same weight, respectively. Morphometric analysis revealed that (i) the mean cell volume was significantly larger and, consequently, the number of parathyroid cells lower expressed per 1 mm3 tissue and (ii) the surface area of the Golgi complex was larger expressed per mean parathyroid cell volume and per 1 mm3 tissue in female rats than in males. Diversity in cell volume seems to depend on age rather than on sex, whereas diversity in the Golgi complex is considered to be sex related. The physiological implications remain to be clarified. PMID- 1746235 TI - Effects of physical training during the growth on the granulation of myo epithelioid cells of the rat kidney. AB - The behaviour of the granulation of the myo-epithelioid cells of the juxtaglomerular apparatus of the kidney and its relationship with the plasma concentrations of renin, sodium and potassium, and plasma osmolality have been studied in male and female Wistar rats that have been subjected to a programme of moderate physical exercise throughout their period of growth. In the trained rats a significant increase in the juxtaglomerular granulation index and a significant decrease in plasma renin concentration has been observed, the changes being more prominent in the female animals. Moreover in the trained rats significant increases in plasma sodium, potassium and osmolality have been observed. PMID- 1746236 TI - Morphological study of the development of the disseminate prostate in intact and castrated male pigs aged two to six months. AB - The light-microscopical and ultrastructural differentiation of the disseminate prostate was studied in 12 boars and 8 barrows, ranging in age from 8 to 28 and 12 to 27 weeks, respectively. The barrows had been castrated at the age of 8 weeks. In young boars the prostate is organized in an inner zone and an outer zone. The glandular tubules of the latter are more differentiated than those in the inner zone. Sexual maturation in the prostate is characterized by almost complete reduction of the inner zone and concomitant enlargement of the outer zone. This differentiation of the inner zone occurs progressively and is manifested by a higher density of the glandular tubules, by a decrease in the number of basal cells and by an increase in the secretory tubular cells containing more microvilli, organelles and secretory vesicles. A few weeks after castration, the characteristic morphology of the undifferentiated inner zone is found throughout the entire glandular layer. The number of glandular tubules in barrows has decreased, and their cells show minimal secretory activity, nuclear indentations and a decrease in their organelles. A further castration effect is vacuolization of the perinuclear cytoplasm in numerous glandular cells. PMID- 1746237 TI - Morphometric study of ventricular myocardial cells in the bat (Pipistrellus pipistrellus), hamster (Mesocricetus auratus) and Wistar rat. AB - A comparative morphometric study of ventricular myocardial cells of the West African insect-eating the Pipistrellus pipistrellus, the hamster and the rat revealed significant differences in volume fractions of mitochondria myofibrils, lipid bodies and T tubules. In the cells of the bat, mitochondria constitute 35% of cytoplasmic volume compared with 29 and 30% in the hamster and rat, respectively. Notably, crista density is much higher in the bat cells (3.58 x 10(5) cm-1) than in those of the hamster (2.59 x 10(5) cm-1) and of the rat (2.48 x 10(5) cm-1). Myofibril concentration is 40% in the bat, 53% in the hamster and 55% in the rat. There is greater numerical density of lipid bodies in the bat (212.27 x 10(9) cm-3) than in the hamster (139.20 x 10(9) cm-3) and in the rat (114.00 x 10(9) cm-3). The volume occupied by T tubules is 0.02 in the bat and hamster, and 0.009 in the rat. These differences suggest structural design for efficient metabolic activity in the bat which, among mammals, has high exercise tolerance. PMID- 1746238 TI - Kinetics of spermatogenesis in the wild squirrel Funambulus palmarum (Linnaeus). AB - The paper describes in detail the morphology and kinetics of germ cell associations, pattern of mitotic divisions, frequency distribution of different cellular associations (stages) and percent degeneration of various germ cells in the squirrel in which spermatogenesis in adults occurs all year round. Eighteen steps of spermiogenesis were identified based on the development of the acrosomal system using PAS-haematoxylin. These were appropriately divided into Golgi, acrosome, cap and maturation phases. Thirteen types of cellular associations or stages (I-XIII) were characterized along the length of the seminiferous tubule which repeated itself in space and time constituting the seminiferous epithelial cycle (CSE). Of the 18 steps of spermiogenesis, the first 13 were associated with stages I-XIII, respectively, and the rest with the first 9 stages. Spermiation occurred in stage IX. Seven types of spermatogonia [A0, A1, A2, A3, A4, intermediate (In) and B type] were identified based on their shape, size and nuclear morphology. A0 spermatogonia are pale in appearance with homogeneously distributed chromatin surrounded by a thin nuclear membrane. These are present in all stages. A1 are oval in shape and possess a thicker nuclear membrane. They are found in stages VI-X. The chromatin material undergoes progressive condensation from A1 to A4 making the last generation of spermatogonia appear darker. The In spermatogonia which are derived from A4 are morphologically similar to them but smaller in size. The B-type spermatogonia derived from the In types possess a typically round nucleus with uniformly condensed chromatin material underneath the nuclear membrane. The spermatogonia divide mitotically at fixed stages of the CSE giving rise to their next generations. Thus, A-type spermatogonia divide at stages X, XIII/I, IV and V, while In divide at stage VI. During each CSE of the squirrel, 5 peaks of mitosis occur. There is a single generation of B-type spermatogonia. These differentiate into primary spermatocytes and undergo meiosis or maturation divisions which enter to form spermatids. The A4 which divide differentially in stage VI give rise to In- and A1-type spermatogonia. Therefore, A4 spermatogonia form renewing stem cells. Based on the above pattern of spermatogonial mitosis a model for stem cell renewal in the squirrel is proposed. The percentage degeneration of germ cells varied with the cell type. During a single CSE of the squirrel, a total of 42.09% germ cells were found to degenerate. An attempt is made to compare and contrast the kinetics of spermatogenesis in the wild squirrel with that of the other rodents studied so far. PMID- 1746239 TI - Identification of point scores at stage 23 in the rat according to the system of scoring in the human embryo. AB - The 8-point scores, evidenced in the human embryo of stage 23, were analysed in the rat at the end of the embryonic period. Eleven OFA rat embryos-crown-rump length 16 mm, 16th postcoital day--were submitted to serial histological sections with graphic reconstruction. The 8 internal key structures, previously observed in man by O'Rahilly--i.e. the cornea, optic nerve, cochlear duct, adenohypophysis, vomeronasal organ, submandibular gland, metanephros and humerus- were readily recognizable. The identification of these anatomical features permits to determine the end of the embryonic period and to obtain a clear distinction between this and the fetal period. The similarity and the presence of the same organs in man and rats at this period of development permits to consider the rat as a good experimental model of teratology. PMID- 1746240 TI - Correlation of myosin isoforms with anatomical divisions in equine musculus biceps brachii. AB - The biceps brachii of horses is subdivided into a lateral and medial head. Electrophoresis of samples from the lateral head revealed three slow-migrating native myosin isoforms, including one that does not correspond to slow myosin isoforms described for other mammalian muscles. In contrast, the medial head contained a single slow isoform. Both the lateral and medial heads contained three fast-migrating isoforms corresponding with the FM-2, FM-3 and FM-4 isoforms reported for other mammalian fast-twitch muscle fibers. Electrophoresis of myosin heavy chains (MHCs) revealed only two MHC bands, one fast-migrating band that comigrates with rat type I MHC and a second slower-migrating band that comigrates with rat type IIa MHC. Quantitation of the histochemical data is correlated with densitometric analysis of MHCs in the medial and lateral heads of biceps brachii and is consistent with previously hypothesized functional specializations of this muscle. PMID- 1746241 TI - Predicting beneficial response to a protein-redistribution diet in fluctuating Parkinson's disease. AB - To identify factors that might help in predicting the benefit to be gained from a protein-redistribution diet (PRD) we subjected 26 parkinsonian patients with motor fluctuations refractory to optimal timing and dosage of levodopa plus bromocriptine to a 2,000-2,500 Kcal., 65-80 g/d protein containing diet maintained for 8-12 weeks. Fifteen patients were eligible for evaluation, 10 of whom being benefited by the PRD (79 percent reduction in the mean "off" time in "on-off" charts). When the duration and pattern of the fluctuations were compared in the 10 diet-benefit patients with those in 5 diet-failure patients only dose failures consistently occurring postprandially were resolved by the PRD. Wearing off failures responded unpredictably while random "on-off" fluctuations were present only in the diet-failure group. Nocturnal akinesia and peak-dose dyskinesias often worsened. In no patient "on"-time quality was modified by the diet. In addition, the diet-failure group was characterized by a younger mean age at onset (p less than 0.05) and by longer duration in their fluctuations (p less than 0.001). Though requiring confirmation in a larger series, our results suggest that parkinsonian patients showing fluctuations over prolonged periods, particularly those having a pattern of random "on-off" oscillations in motor performance and dose-failures unrelated to meals are unlikely to benefit from a PRD. PMID- 1746242 TI - Acute hemorrhagic leukoencephalitis. AB - We report an autopsy proven case of acute hemorrhagic leukoencephalitis. There was a very rapid evolution leading to death in less than 24 hours. CT of the brain revealed widespread hypodensities in both frontal lobes. In the cerebrospinal fluid as well as in the peripheral blood, there was a moderate leucocytosis. The literature is reviewed. PMID- 1746243 TI - Sympathetic skin response versus maximum motor and sensory conduction velocity to detect subclinical neuropathy in non-insulin-dependent diabetics. AB - Conventional motor (MCV) and sensory conduction velocity (SCV) of the ulnar (UN), peroneal (PN) and median nerves (MN) and the areas of sympathetic sudomotor response (SSR) recorded from the middle finger were measured on both sides in 20 normal and 20 non-insulin-dependent diabetic (NIDD) subjects. Conventional statistical tests (t test, linear correlation coefficient r) and discrimination analysis were applied to the above electrophysiological parameters. To evaluate the capability of the tests to separate NIDD diseased from normal nerves, the results were represented as generalized distances, i.e., difference between mean discriminant normalized combinations adjusted for intra-group variability. The r values were 0.92 (P less than 0.01) for the UN, 0.40 (P greater than 0.05) for the PN, and 0.86 (P less than 0.01) for the MN sensory action potential (SAP) amplitudes. No significant differences were found for normalized latencies. The r values of the SSR areas were 0.62 (P less than 0.01) at the right and 0.77 (P less than 0.01) at the left, homolaterally to the side of stimulation. SR and MCV generalized distances were 1.35 and 1.39, respectively. The discriminating power of SSR, MCV and SCV considered together was higher (2.40) than that of MCV and SCV (1.70). Since motor, sensory and autonomic alterations often did not coexist in NIDD, it was possible to find at least one type of involvement in most of the diabetic subjects. PMID- 1746244 TI - Familial hemangioblastoma and von Hippel-Lindau's disease: case report. AB - Thirty-five members of a family affected with von Hippel-Lindau's disease (VHL) were examined and lesions were found in nine of them. Four of the lesions were located in the central nervous system; two cerebellar, one spinal, one cerebral. Eye lesions were present in eight of the nine patients and complications developed in seven; six unilateral and one bilateral blindness. Both mortality and morbidity were found to be higher than in other series. This is attributed to insufficient screening of the patients with familial VHL, the late diagnosis was established only after the onset of complications. The importance of screening tests in VHL risk patients is emphasized. PMID- 1746245 TI - Intraneural ganglionic cyst of the common peroneal nerve: case report and review of the literature. AB - The authors report a case of compression of the peroneal nerve by an intraneural ganglionic cyst. The chief complaint is generally a lateral upper leg pain occasionally associated with foot drop and swelling of the upper tibiofibular joint. In our case, the disease was revealed by a tentative intraarticular injection of betamethasone. Early microsurgical treatment remains the only way to avoid permanent motor sequellae. PMID- 1746246 TI - Tribute to a global research programme on reproductive health. PMID- 1746247 TI - The Swedish Insemination Act. PMID- 1746248 TI - Endothelin--a potent constrictor of small myometrial arteries of term pregnant women. AB - This study was performed to evaluate the in vitro effects of a new polypeptide, endothelin-1 (ET-1) on small intramyometrial vessels in comparison with the action of noradrenalin (NA). In connection with cesarean section, myometrial biopsies were obtained and small arteries (100-500 microns in diameter) were excised. Cylindrical segments of these vessels were used for registration of contractile activity after administration of ET-1 and NA. ET produced vasoconstriction and was approximately three times as powerful and 70-fold as potent as NA. It is suggested that ET may be involved in the regulation of human utero-placental blood flow. PMID- 1746249 TI - Prediction of fetal outcome by Doppler examination and by the non-stress test. AB - Ninety-four women with high-risk pregnancies were referred to the Aker University Hospital, Department of Obstetrics, and monitored by Doppler velocimetry and conventional cardiotocography. The peak systolic/end diastolic (A/B) ratio was measured in the velocity waveform obtained in the umbilical artery blood flow. The non-stress test (NST) was classified according to the Fischer scores. In this mixed group of high-risk pregnancies, the sensitivity of the A/B ratio to predict fetal growth retardation was 71%, predictive value 57% and specificity 77%. The corresponding values for NST were 39%, 65% and 90%. It is concluded that Doppler velocimetry is more sensitive than cardiotocography for identifying fetal growth retardation. In an attempt to further improve the detection rate of fetal pathology, the cases with abnormal NST scores were added to those with high A/B ratios and collectively defined as abnormal. In consequence, only an insignificant improvement in sensitivity (79%) could be achieved. When the A/B ratio is normal, there seems little justification for expending time, effort and resources in routine use of cardiotocography. PMID- 1746250 TI - Evaluation of fetal and neonatal mortality at the University Hospital of Tromso, Norway, from 1976 to 1989. AB - To investigate developments in perinatal care, all fetal and neonatal deaths among those born after at least 24 weeks of gestation at the University Hospital of Tromso, Norway from 1976 to 1989, were subjected to medical audit. A decrease in total mortality rate was found when based on maturity (greater than or equal to 24 weeks; 19.9-13.4%; p less than 0.01), and/or birth weight (greater than or equal to 500 g; 19.2-13.4%; p less than 0.05). This was mainly due to a decrease in fetal deaths (14.8-6.6%; p less than 0.0001). Deaths during labor (5.4-1.1%; p less than 0.001), and deaths before the onset of labour (9.4-5.5%; p less than 0.05) declined. The neonatal death rate remained virtually constant (5.2-6.8%). The incidence of conditions affecting the placenta and the umbilical cord, causing asphyxia and intra-uterine growth retardation, declined, from 9.2 to 5.0% (p less than 0.01), as did that caused by immaturity (2.8-1.3%; p less than 0.05). The rates of death caused by cerebral hemorrhage, respiratory distress syndrome, infections, and malformations did not change. There was no significant proportional change in the causes of death from the first to the last period. The rate of fetal death following suboptimal care declined (2.4-0.4%; p less than 0.01), while the corresponding neonatal death rate remained unchanged (0.9-1.1%). The proportions of both fetal and neonatal deaths occurring after suboptimal care were low (fetal: 16.2, 8.8, and 5.6%; neonatal: 17.1, 23.5, and 16.2%). These differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746251 TI - Pericardial effusion in normal pregnant women. AB - Fifty-two normally pregnant women underwent echocardiography to examine their pericardium in the first, second and third trimester. Pericardial effusion was noted in 15.3% of the women (n = 8) in the first trimester, 19.2% (n = 10) in the second trimester and 44.2% (n = 23) in the third trimester of pregnancy. Pericardial effusion during pregnancy was found to be completely resolved in all patients who underwent an echocardiogram 6 weeks post delivery (n = 11). There was no statistically significant difference in age, hemoglobin, total protein, albumin/globulin ratio or mean blood pressure during pregnancy between those who developed pericardial effusion and those who did not. The frequency of occurrence of pericardial effusion in primigravidas at 69.2% (9/13) was higher than that in multigravidas, with a ratio of 35.9% (14/39), the difference being statistically significant (p less than 0.025). The frequency of occurrence of pericardial effusion in patients who gained more than 12 kg during pregnancy at 67.7% (11/17) was higher than in patients who gained less than 12 kg, with a ratio of 34.3% (12/35), the difference being statistically significant (p less than 0.025). PMID- 1746252 TI - Incidence of fetal chromosome abnormalities in insulin dependent diabetic women. AB - In order to screen for fetal neural tube defects and chromosome abnormalities, amniocentesis was carried out in 334 women with insulin-dependent diabetes mellitus (IDDM) between 1979 and 1987. Two cases (0.6%; 95% confidence limits 0.1 2.2%) of fetal chromosome abnormality were found: one case of Klinefelter's syndrome and one case of de novo translocation. This is comparable to the overall incidence of chromosome abnormality found at birth and is also comparable to the incidence of fetal chromosome abnormality (1.0%) found by amniocentesis at our Department in a group of 2,264 young non-diabetic women with little risk of contracting genetic disorders. The results suggest that maternal IDDM does not increase the risk of fetal chromosome abnormality and consequently screening by amniocentesis for chromosome abnormalities among diabetic women does not seem to be indicated. PMID- 1746253 TI - Pregnancy outcome in patients undergoing long-term hemodialysis. AB - Three uremic patients receiving hemodialysis for more than 5 years became pregnant and proceeded to the third trimester. A variety of complications were noted, including threatened abortion, vanished twin, preterm premature rupture of membranes, polyhydramnios, intra-uterine fetal death, intra-uterine growth retardation, premature labor and hypertension. Two of these 3 mothers gave birth to healthy babies under the management of the high-risk pregnancy team. PMID- 1746254 TI - The relationship between alcohol consumption during pregnancy and infant birthweight. An epidemiologic study. AB - Heavy alcohol consumption during pregnancy has been consistently associated with inhibited intra-uterine growth; however, the effect of social drinking is not yet clear. The relationship between moderate drinking and low birth weight (less than 2,500 g) among a nationally representative sample of white married mothers who gave birth to singletons infants in the National Natality Survey (1980) is analysed here. Alcohol consumption during pregnancy was significantly associated with birth weight (p less than 0.02). Moreover, there was a gradient of risk in low birth weight associated with increasing amount of alcohol ingestion during pregnancy. There was a significant association between the mean birth weight of the singletons across different categories of alcohol intake (p less than 0.0001). The difference between the mean birth weight of the singletons among moderate drinkers compared with nondrinkers was also statistically significant (p less than 0.005). These relationships remained after simultaneously adjusting effects of the confounding variables gestational age, parity, smoking, weight gain, maternal age and education in multiple regression analyses. These findings confirm earlier reports of a relationship between alcohol use during pregnancy and decreased birth weight. Additionally, it is shown here that for moderate alcohol use during pregnancy, there is an adverse effect on the birth weight. PMID- 1746255 TI - Smoking cessation in pregnancy. Mode of intervention and effect. AB - Three groups (n = 50 each) of pregnant smokers wanting to quit the habit were assigned to three different intervention programs around their 18th week in pregnancy. Group 1 participated in a smoking cessation program offering several self-help methods; group 2 attended a doctor's information meeting at the hospital; and group 3 received a pamphlet on the deleterious effects of smoking in pregnancy. For Group 4, the control group, there was no intervention. In all three intervention groups, more than one-third reduced their smoking to almost half, while 38% quit altogether in group 1, compared with less than 10% in groups 2 and 3. Twelve months later, 16%, 6% and 8% respectively, remained abstinent in the three groups. In groups 2 and 3, abstinence proved to be of the same magnitude as in the control group. We conclude that smoking in pregnancy, being one of the few amenable to risk factors affecting the perinatal death statistics, demands an active smoking cessation program during pregnancy led by specially trained health professionals. PMID- 1746256 TI - The influence of epidural blockade and pethidine administered during delivery on neonatal myocardial performance. AB - The aim of the present study was to investigate whether obstetric analgesia with an epidural blockade (Marcaine, bupivacaine hydrochloride, 141.5 +/- 56.8 mg) and pethidine (95.0 +/- 30.7 mg) influenced neonatal myocardial function following vaginal delivery. Left ventricular output and other left ventricular function indices were measured 5.6 +/- 4.3 h postpartum with Doppler and M-mode echocardiography in a group of healthy, full-term, appropriate-for-gestational age infants (n = 10) whose mothers had received both bupivacaine and pethidine during delivery, and in a similar group of newborn infants (n = 10) whose mothers had received only nitrous oxide/oxygen analgesia. In 7 of the 10 infants in each groups, a second assessment of myocardial function was performed 21.7 +/- 4.6 h post partum. There were no significant differences in any of the variables used to assess left ventricular function at either of the measurement points between the group of infants whose mothers had received bupivacaine/pethidine during delivery, and the group of infants whose mothers had received nitrous oxide/oxygen analgesia only. PMID- 1746257 TI - Oxytocin or saline injected intra-umbilically did not influence the third stage of labor. AB - The injection of varying volumes of normal saline solution, alone or with oxytocin, into the umbilical vein immediately after delivery was studied in 125 normal women delivered at term. Thirty seconds after cord clamping, either 20 ml (group 1, n = 25 women), 30 ml (group 2, n = 25) or 40 ml (group 3, n = 25) of normal saline solution alone, or oxytocin 10 units in 20 ml saline solution (group 4, n = 25) or oxytocin 10 units in 40 ml saline solution (group 5, n = 25) were injected into the umbilical vein 1 cm from the introitus just proximal to the umbilical clamp. The mean (+/- SD) duration of placental expulsion was similar in the five study groups. We conclude that neither the volume of the solution nor the oxytocin injected intra-umbilically has any effect on the duration of the third stage of normal labor. PMID- 1746258 TI - The use of episiotomy in primiparas in Sweden. A descriptive study with particular focus on two hospitals. AB - This study has examined the use of episiotomy (Ep) in primiparas on all labor wards (65) in Sweden, focusing on two hospitals in particular. The information was obtained by means of a questionnaire and from original medical records at the two hospitals. Whereas the mean incidence of Ep for the whole country was 30%, we found a wide variation (9-77%) from hospital to hospital. When delivery positions were compared, the lowest Ep rate was reported from those hospitals where women frequently used "alternative positions". The results suggest that efforts should be directed to a more restrictive use of Ep in normal delivery. PMID- 1746259 TI - Heterotopic pregnancy following in vitro fertilization. AB - We report 4 cases of heterotopic pregnancy following in vitro fertilization. All 4 patients were treated by surgical removal of the ectopic pregnancy products. In 3 patients, the intra-uterine fetus was alive prior to surgery. Two of the 3 gave birth to a healthy baby while the third pregnancy has progressed uneventfully for 12 weeks since the operation. PMID- 1746260 TI - Experience with GnRH agonists in an in vitro fertilization (IVF) program. AB - The experience using pre-treatment with GnRH-agonists in an IVF-program are reported. 55 patients having a 'poor response', premature LH surge, or follicular luteinization in previous treatment cycles were treated for a total of 68 cycles. Therapy with GnRH agonists was initiated in the midluteal phase, and given by self-administration subcutaneously. Stimulation started with exogenous gonadotropins on a fixed day (Saturday) after pituitary desensitization had first been obtained, and resulted in all follicular punctures being performed on weekdays. Five treatment cycles (7.4%) were cancelled because of 'poor response'. Where the indication for GnRH-agonist therapy was previous 'poor response', a cancellation rate of 36.4% was observed, whereas a cancellation rate of only 1.8% was found in the other indication groups (p less than 0.001). Altogether 26 clinical pregnancies were achieved, five of these ending in a spontaneous abortion. The rate of deliveries was 33% per oocyte retrieval, and 40% per pre embryo replacement. PMID- 1746261 TI - Ultrasonically guided retrieval of occult IUD in early pregnancy. AB - The risk of spontaneous abortion and intra-uterine infections in pregnancies associated with an intra-uterine conceptive device (IUD) is well documented. There is a general agreement regarding the desirability of removing the IUD as soon as the pregnancy is diagnosed. When the string is not visible, the proper management is controversial. This study reports the successful retrieval of occult IUD in early pregnancy under ultrasonic guidance in 8 out of 9 women. In the one case where we failed to remove the IUD, the women chose to terminate the pregnancy by legal abortion. Seven women completed their pregnancy, while one experienced a spontaneous abortion. We consider the removal of the occult IUD in pregnancy under ultrasonic guidance to be a useful procedure. PMID- 1746262 TI - Concomitant endocervical curettage and cervical conization. AB - We present a series of 94 endocervical curettages (ECC) performed directly after cutting a cervical cone specimen. In 7 patients the ECC gave insufficient material for a histological diagnosis, but in 9 patients it contained CIN. The top of the cone contained CIN in 17 cases. The correlation between the histological results from the top of the cone and the ECC was poor. The presence of persistent disease after conization was studied in relation to both the status of the top of the cone and to the ECC. For the latter we found a sensitivity of 0.50 and a specificity of 0.95. The top of the cone showed a sensitivity of 0.80 and a specificity of 0.88. It is concluded that ECC is of little additional value in predicting persisting disease. PMID- 1746263 TI - Transcervical resection of endometrium and fibroids. Initial complications. AB - Transcervical resection of endometrium--and of submucous fibroids when present- seems to represent a new alternative to hysterectomy for patients with uncontrolled bleeding disorders. In the present study, we report our initial experience with the first 20 patients treated with a standard, rigid urological resectoscope. Resection of endometrium--and of fibroids when present--was carried out under general anesthesia. The uterine cavity was distended and irrigated with glycine 1.5%. Two perforations occurred, but damage to neighboring organs was not seen. In one patient, copious bleeding was encountered and hysterectomy became necessary the following day. Clinical signs of postoperative infection occurred in 3 patients. Otherwise, no major morbidity was seen during or after the procedure. In 2 patients with persistent metrorrhagia, re-resection was performed after 2-3 months and satisfactory bleeding control achieved. At the 3-month follow-up, 2 further patients complained of persistent bleeding and had an abdominal hysterectomy performed. In the remaining patients, satisfactory bleeding control was reported at the 6-month follow-up. Although large series are needed to assess the complications associated transcervical resection of the endometrium, the technique may be applied in departments with experience in routine hysteroscopy, and the approach seems to represent an attractive alternative to hysterectomy. PMID- 1746264 TI - Hemodialysis rescued the mother in a case of severe chronic renal failure accompanied by perirenal hematoma due to HELLP syndrome. AB - We present a case of severe maternal renal failure, accompanied by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). Since her renal function deteriorated in addition to the anemia and thrombocytopenia from 25 weeks' gestation, hemodialysis was performed three times a week. Unfortunately intra-uterine fetal death suddenly occurred at 30 weeks' gestation, and maternal right perirenal hematoma was diagnosed after delivery. The anemia and thrombocytopenia improved dramatically and the perirenal hematoma resolved uneventfully by late puerperium. The management of severe maternal renal failure with HELLP syndrome is described. PMID- 1746265 TI - Severe ovarian hyperstimulation syndrome complicated by ectopic pregnancy. PMID- 1746266 TI - Twin pregnancy with a fetus in each half of a uterus didelphys. AB - A rare case of a twin pregnancy with a fetus in each half of a uterus didelphys (double uterus, double cervix and septate vagina) is reported. A longitudinal vaginal septum and two portios were detected during the first labor of this patient. During her second pregnancy ultrasonography was performed in the 16th week, and pregnancy was detected in each half of the double uterus. Both fetuses were of similar size and corresponded to the gestational age. A completely separated double uterus was confirmed by ultrasonography. In the 38th week a female and a male infant were delivered by cesarean section. The follow-up of this pregnancy and the management of the labor are reported. PMID- 1746267 TI - Psychotic exacerbation attributed to low-dose bromocriptine treatment of galactorrhea and hyperprolactinemia. AB - Low-dose bromocriptine administered for antipsychotic drug-induced hyperprolactinemia and galactorrhea precipitated an acute psychotic state in a female patient. Discontinuation of the bromocriptine and increase in antipsychotic dosage resulted in complete remission. We advise caution in the use of bromocriptine especially in patients with a pre-existing psychiatric history and recommend monitoring for changes in mental status when bromocriptine is prescribed. PMID- 1746269 TI - Ultrasound in the diagnosis and treatment of ovarian tumors. PMID- 1746268 TI - Monochorionic monoamniotic twins--the most precarious of twin pregnancies. AB - Monochorionic monoamniotic twins have a high perinatal mortality rate. Death usually occurs before 24 weeks' gestation, mainly because of cord entanglement, prematurity, congenital anomalies or twin-to-twin transfusion. These possibilities should be taken into account when twin pregnancies are detected at the ultrasound screening between 17 and 20 weeks' pregnancy. We report here a case where monochorionic monoamniotic twins were born at 34 weeks, with massive cord entanglement and we describe the antenatal care at our clinic. PMID- 1746270 TI - Human sperm characteristics before and after preparation for in vitro fertilization. PMID- 1746271 TI - Doppler ultrasound recordings of placental blood velocity waveforms. PMID- 1746272 TI - Phenotype of the arterial smooth muscle cell during fetal development, ageing, and atherosclerosis. PMID- 1746273 TI - Hormonal influences in women, as reflected in cognitive function, libido, sexual behaviour and premenstrual symptoms. PMID- 1746274 TI - Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome. PMID- 1746275 TI - Prognostic factors in ovarian carcinoma. A clinicopathologic study with special reference to mitotic counts, nuclear morphometry and DNA cytometry. PMID- 1746276 TI - Nordic symposium on gynecological oncology, Svalbard, Norway 1990. Consensus statements. PMID- 1746277 TI - Violence among psychiatric inpatients. AB - A considerable body of evidence suggests increasing levels of violence among psychiatric inpatients. The literature on the subject is reviewed, highlighting correlates of violence among psychiatric patients and methodological flaws in the published literature. Improvement in the definition of violence and the methodology as well as future areas of research are discussed. PMID- 1746278 TI - Standardized Assessment of Depressive Disorders: a replicated study from northern India. AB - A total of 91 subjects with depressive disorder have been studied using the WHO standardized Standardized Assessment of Depressive Disorders (SADD). The 10 most frequently reported symptoms were sadness, anxiety, joylessness, lack of energy, hopelessness, loss of interest, disruption of social functioning, irritability, loss of ability to concentrate and lack of appetite. The results of this study are compared with other available work on SADD. PMID- 1746279 TI - Comparative study of affective disorders in three Asian countries. II. Differences in prevalence rates and symptom presentation. AB - This study used standardized diagnostic criteria and method to investigate both prevalence rates and nature of symptoms of depressive disorders in three Asian centres--Nagasaki, Shanghai and Seoul. Of the patients who visited a psychiatric clinic in each of the 3 centres for the first time, over 20% suffered from depression. Unlike previous reported prevalence rates for Asian countries, these results suggest that rates in Asia may not be much lower than those reported in Western countries. Although prevalence rates of depression were similar in all 3 centres, differences in symptoms were noted. PMID- 1746280 TI - Differences between schizophrenics born in winter and summer. AB - A total of 1814 patients were studied from the Mississippi State Hospital with a DSM-III diagnosis of schizophrenia and aged 15-39 years at the time of admission. The 634 schizophrenics with a birth date between 1 December and 31 March were compared with the 1180 born between 1 April and 30 November for age of admission, race, sex, marital status, duration of initial admission and clinical subtype. The only significant difference between the variables was the duration of the first admission: winter-born patients had a shorter psychiatric hospitalization than summer-born schizophrenics. These findings are discussed in accord with similar studies. PMID- 1746281 TI - Validation of the Hospital Anxiety and Depression Scale in Arab patients. AB - The Hospital Anxiety and Depression Scale (HADS) was administered to psychiatric outpatients with various diagnoses to assess its validity. The study was also designed to find out whether HADS can differentiate between diagnostic groups based on depression and anxiety symptoms. HADS was able to discriminate patients from controls at a sensitivity of 79% and specificity of 87%. HADS was much less sensitive, specific and diagnostically accurate in identifying anxiety and depressive disorders in the experimental group at a cut-off point of 13 and 10 respectively for both conditions. Possible psychological, social and psychiatric reasons for the results are discussed. PMID- 1746282 TI - Gender differences in depression: historical changes. AB - Depression has been widely reported to be more prevalent among females than among males. In this study we demonstrate that gender differences in depression occur only among individuals born during particular historical periods, and test the utility of a model focusing on changes in women's opportunities for academic and professional achievement in predicting periods of significant gender differences in depression. Based on reanalysis of data reported by Klerman et al., we find gender differences in depression among people 40 years of age and older to be high among cohorts that reach adolescence during periods of increasing opportunities for female achievement. Among cohorts that reach adolescence during periods of stable or decreasing opportunities for women, gender differences in depression are not significant at any age. PMID- 1746283 TI - Reliability of the draft diagnostic criteria for research of ICD-10 in comparison with ICD-10 and DSM-III-R. AB - The reliability and ease of use of DSM-III-R and the clinical and research versions of ICD-10 were assessed by 5 psychiatrists working in pairs. They diagnosed 60 patients. All 3 systems showed similar and high interrater and intersystem agreement for major diagnostic categories but not for subcategories. A number of implications of these results are discussed. PMID- 1746284 TI - Premorbid personality and positive and negative symptoms in schizophrenia. AB - The relationship between premorbid personality and schizophrenic symptoms assessed by the Scales for the Assessment of Positive and Negative Symptoms was explored in 115 DSM-III-R schizophrenics. The frequencies of normal, schizoid schizotypal and other DSM-III-R personality disorders were 44%, 39% and 17%. Affective flattening and alogia were significantly more frequently present and severe in the schizoid-schizotypal group than in the rest of the patients. There were no differences in positive symptoms. It is suggested that, in some cases, negative symptoms are merely the persistence or exacerbation of schizoid traits present prior to the emergence of schizophrenic symptoms. These results should be cautiously interpreted because the premorbid personality was diagnosed in a retrospective way and the negative symptoms were assessed cross-sectionally. PMID- 1746285 TI - Effect of medical school stress on the mental health of medical students in early and late clinical curriculum. AB - Earlier research has shown that medical students in the United Kingdom and the United States report a higher level of nervous symptoms than the general population. To better understand how medical students in Norway compare with these findings, 299 male and female students in the clinical curriculum at the University of Oslo were asked to complete a questionnaire about themselves and their mental health. Medical students in Norway do not differ from the general population in mental health. However, the students report a lower level of general self-esteem than the general population. The male students had more nervous symptoms and a less general self-esteem than the female students compared with the general population. This research also shows that medical school stress is a good predictor of nervous symptoms even when psychosocial variables such as marital or cohabitation status, confident other and general self-esteem are taken into consideration. PMID- 1746286 TI - Patterns of outcome in schizophrenia in Hong Kong. AB - A total of 153 schizophrenic subjects were included for outcome assessment in different aspects of their life functions. The same group of subjects was followed-up 1 year later to assess the consistency of their outcome pattern. A factor analysis on the outcome measures was conducted, and 5 independent factors were noted. Outcome on symptomatic control was most favourable but less consistent over time. Psychosocial deficits, on the other hand, were more enduring and noted in a significant proportion of the subjects. PMID- 1746287 TI - Involuntary commitment in Greenland, the Faroe Islands and Denmark. AB - Greenland, the Faroe Islands and Denmark have common legislation and registration for involuntary commitment. Commitment rates were calculated based on information from the Danish psychiatric register for 1984-1988. Direct standardization with the Danish male and female population as a standard population (1984-1988) was carried out to evaluate differences in rates. An increased risk of commitment was found in Greenland, where the crude commitment rate was 43.5 commitments per 100,000 inhabitants. The commitment rate on the Faroe Islands was 19.2 per 100,000 and 24.2 per 100,000 in Denmark. The relative risk of commitment in Greenland vs Denmark was 2.0 (1.6-2.4) and increased to the same extent for both sexes. Young men constituted a high-risk group for commitment in Greenland. Males between 15 and 34 years accounted for 55% of the total number of commitments in Greenland. The high relative commitment risk in Greenland is related to higher homicide rates, lower psychiatric bed availability, reduced access to psychiatric treatment, small settlements and increased alcohol consumption and violence than in Denmark. PMID- 1746288 TI - A modern therapeutic approach for chronically mentally ill patients--results of a four-year prospective study. AB - A 4-year prospective study was carried out on 53 chronically mentally ill patients living in a differentiated complementary residential complex. Our main question was how the lives of these patients develop, as reflected in their psychological wellbeing, working capacity, therapeutic requirements and any necessary periods of rehospitalization. At the end of a 4-year rehabilitation period, 50% of the patients were living in sheltered communities and about 25% on their own. Only 10% had returned to the psychiatric hospital as long-term patients. The psychological findings were characterized by apathetic, depressive and psycho-organic syndromes (AMDP system) and were subject overall to minimum variation. Very few patients succeeded in obtaining work on the general labour market, but the work available on the sheltered labour market was suitable for a large proportion (40%) of them. All patients were undergoing medical care after 4 years. Patients suffering from chronic mental disorders can be cared for in the community even after long-term hospitalization. Special success has been achieved with rehabilitation in the residential sphere. Adequate care implies numerous services to ensure that patients are integrated into the labour market, to help establish contacts and to enable chronically ill patients to take part in social and cultural life. Most patients retain a considerable degree of psychological disturbance and are permanently dependent on psychiatric therapy or psychosocial care. On the other hand, they benefit from the fact that their living circumstances are largely normal and that they have higher degree of personal autonomy. PMID- 1746289 TI - Reliability and validity of the Chinese versions of the Scales for Assessment of Positive and Negative Symptoms. AB - This 4-center study assesses the reliability and validity of the Chinese versions of the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Interrater reliability, short-term test-retest reliability, and internal consistency were excellent; intraclass correlation coefficients and Cronbach alphas for the overall scores were all over 0.8. The strong correlation of the scales with an independently assessed parallel measure (the Chinese version of the Brief Psychiatric Rating Scale) and the separate positive and negative factors found with principal components analysis confirm the construct validity of the instruments. These findings demonstrate the importance of culturally sensitive revision and rigorous psychometric evaluation of Western instruments prior to their use in non-Western cultures. PMID- 1746290 TI - Greek version of the General Health Questionnaire: accuracy of translation and validity. AB - The purpose of this study was to examine the accuracy of translation and to test the validity of the Greek version of the General Health Questionnaire (GHQ). In the translation study, the English and the Greek versions of the GHQ were administered to a sample of 50 bilingual respondents. The internal consistency, item-by-item and the subject-by-subject analysis have shown that the 2 versions are equivalent and therefore the Greek translation is highly accurate. In the validity study, 100 consecutive patients attending an internal medicine outpatient clinic completed the Greek version of the GHQ-60 and were interviewed independently using the Present State Examination (PSE). The validity of the shorter forms of the questionnaire (GHQ-30 and GHQ-28) was tested by disembedding the relevant items from the larger set. The correlations obtained between the scores of the questionnaire and the PSE ratings, as well as all the validity indices (sensitivity, specificity, positive predictive value, negative predictive value and overall misclassification rate) were quite satisfactory for all the GHQ forms, thus confirming the validity of the questionnaire in its Greek version. The best cut-off points as found by receiver-operating characteristics analysis were 11/12 for the GHQ-60, 5/6 for the GHQ-30 and 4/5 for the GHQ-28. The revised (CGHQ) scoring system for the GHQ-30 has not been proved superior to the conventional scoring method. The above results are discussed in relation to the pertinent literature and especially the studies carried out in similar settings and in countries with similar cultural backgrounds. PMID- 1746291 TI - Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. AB - In an attempt to delineate the pathophysiology underpinning the previously reported blunted lymphocyte responses to mitogenic stimulation in depressed patients, we measured the following immune variables in 28 depressives and 10 healthy controls: pre- and postdexamethasone (1 mg orally) lymphocyte responses to various mitogens, such as phytohaemagglutinin (PHA), and the PHA-induced accumulation of interleukin-1 beta (Il-1 beta) and soluble interleukin-2 receptors (sIl-2Rs) in culture supernatants. In the predexamethasone state, we found significantly more mitogen-stimulated blastogenesis in minor depressives vs healthy controls and major depressives. In depressed subjects there was a significant inverse relationship between the severity of illness and the mitogen induced lymphocyte responses. Melancholics exhibited significantly more Il-1 beta accumulation in PHA culture supernatant than healthy controls. In healthy controls--but not in depressed patients--the sIl-2R accumulation perfectly reflects the magnitude of the PHA-induced lymphocyte stimulation. Dexamethasone administration significantly suppressed the lectin-induced blastogenesis and the Il-1 beta production rate in normal volunteers, whereas depressives exhibited dexamethasone nonsuppression in those factors. Healthy controls exhibited significantly less postdexamethasone blast transformation, Il-1 beta and sIl-2Rs accumulation in culture supernatant than the depressed patients. PMID- 1746292 TI - Eating behaviour, drug use, psychopathology and parental bonding in adolescents in Norway. AB - A 12-item version of the Eating Attitudes Test (EAT-12) was constructed and applied at 1-year intervals in a non-referred cohort of 1193 adolescents in Norway aged 13-18 years. Eight percent of the girls scored beyond the chosen cut off point of 9/10 the first time and 9% the second time. Factor analysis demonstrated 3 factors--dieting, bulimia and food preoccupation and oral control. Both the total scores on the EAT-12 and the 3 different factor scores showed a significant relationship between eating behaviour and smoking, level of alcohol consumption, alcohol intoxication, psychopathology and parental bonding. PMID- 1746293 TI - Latent class analysis of organic aspects of obsessive-compulsive disorder in children and adolescents. AB - Organic aspects of obsessive-compulsive disorder (OCD) have previously been described and hypotheses of biological etiology have been suggested. Sixty-one patients, 8-17 years of age, who fulfilled the DSM-III criteria for OCD in a review of the records were compared with 117 matched control patients for organic features. The indicators chosen for an organic concept were neurological signs, more than mild electroencephalographic abnormality, specific developmental disorder and attention deficit, and their defining property of an organic concept was confirmed by latent class analysis. Neurological signs was the most sensitive and specific indicator. Significantly fewer OCD children than control patients were assigned to the organic class. Almost all the types of obsessive-compulsive symptoms were more related to the non-organic class. Such extroverted symptoms as behavioral problems and loss of temper were significantly more frequent in patients assigned to the latent organic class, whereas symptoms of phobia and depressive mood were more often present in patients belonging to the nonorganic class. No difference was found between OCD patients and controls as to frequency of birth complications. The findings do not support the evidence of OCD having signs of major cerebral disturbance found by conventional neuropediatric methods. PMID- 1746294 TI - A comparative study of immune status in panic disorder patients and controls. AB - Alterations of immunocompetence in various mental disorders have been reported. We studied white blood cell counts and immunoglobulin levels in 59 panic disorder patients and 30 controls. The significantly increased IgA levels and tendency toward increase in other immunoglobulins in panic disorder patients suggest an immune dysfunction. PMID- 1746295 TI - Historical and psychiatric aspects of multiple sclerosis. PMID- 1746296 TI - Low high-density lipoprotein cholesterol and other coronary heart disease risk factors in patients with total cholesterol levels greater than 5.17 mmol/L (200 mg/dL) in family practice. A report from CEN. AB - BACKGROUND: A multisite, open-label, prospective study in 327 family practices across the United States analyzed the demography of a large population of dyslipidemic patients and examined the effects of diet and exercise, as well as of gemfibrozil therapy, on serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. METHODS: The 3328 patients enrolled comprised a heterogenous population who had wide age range (20 to 88 years), were of both sexes and various ethnic backgrounds, and had multiple cardiac risk factors. All had a history of serum cholesterol levels of 5.17 mmol/L (200 mg/dL) or more, and some may have been previously identified as having an HDL of 1.03 mmol/L (40 mg/dL). After determining their cardiac risk factor and lipid profiles, eligible patients were assigned to a protocol of diet and exercise, followed by concomitant gemfibrozil therapy, if warranted. Treatment efficacy data will be reported in a subsequent paper. RESULTS: The study population was 60 percent men. Ninety-four percent of the patients were white, 4.1 percent were black, and 1.9 percent were of other races. Women patients tended to be more overweight, and elderly women had more hypertension; they were less likely to have angina pectoris or to have had previous myocardial infarctions, angioplasty, or bypass surgery. The prevalence of low HDL cholesterol (less than 1.03 mmol/L [40 mg/dL]) was substantially higher in men. Statistically significant differences between men and women were observed for mean values of total cholesterol, 6.47 versus 6.84 mmol/L (250.3 versus 264.4 mg/dL); HDL cholesterol, 0.94 versus 1.18 mmol/L (36.3 versus 45.5 mg/dL); LDL cholesterol, 4.62 versus 4.76 mmol/L (178.7 versus 184.2 mg/dL); non-HDL cholesterol, 5.54 versus 5.66 mmol/L (214.1 versus 218.9 mg/dL); and the total cholesterol-HDL ratio, 6.84 versus 5.64. CONCLUSIONS: Current National Cholesterol Education Program (NCEP) guidelines suggest lipoprotein analysis at cholesterol levels between 5.17 and 6.21 mmol/L (200 and 240 mg/dL) only if two or more risk factors are also present. Persons whose total cholesterol values are less than 6.21 mmol/L (240 mg/dL) can still be at risk because of the presence of other cardiovascular risk factors or a low level of HDL cholesterol. In this study, 74.3 percent of men and 41.3 percent of women with total cholesterol greater than or equal to 5.17 mmol/L (200 mg/dL) were also found to have a low HDL level, less than 1.03 mmol/L (40 mg/dL). The prevalence of other risk factors in this patient population was also high: 40.5 percent had hypertension, 9.6 percent had diabetes, and 20.3 percent smoked. These data suggest that routine lipoprotein analysis in the family practice setting could reveal low HDL cholesterol as an additional risk factor in a patient population where other risk factors have already been identified. PMID- 1746297 TI - Neonatal mortality clusters: a new tool for classifying neonatal outcomes. AB - BACKGROUND: A method for assessing general hospital neonatal care performance is needed that is simple, is easy to use, and requires minimal data. METHODS: All neonatal deaths in Washington State obstetric hospitals from 1980 to 1983 were assigned to 10 mutually exclusive neonatal mortality clusters, a new classification method derived from information available on the death certificate. RESULTS: More than one-third (35.3 percent) of all neonatal deaths fell within one of the seven clusters considered to represent potentially preventable causes of death. The rate of possibly preventable deaths was much higher in level III hospitals than in level II or level I hospitals, a finding similar to that observed in other states using different analytic approaches. CONCLUSIONS: Neonatal mortality clusters offer a less complex method of classifying neonatal deaths and assessing hospital performance than other currently used techniques. PMID- 1746298 TI - The epidemiology of bacterial meningitis. AB - BACKGROUND: The incidence by age and causative organism of bacterial meningitis are not known on a community basis. METHODS: The epidemiology of bacterial meningitis in a metropolitan county was studied by identifying all cases admitted to a hospital from 1983 through 1987. RESULTS: The overall incidence of bacterial meningitis was 5 per 100,000 person-years, but numbers of cases ranged from 40 per 100,000 for children younger than 5 years to 1.0 per 100,000 in adults aged between 16 and 64 years. No significant excesses of cases were found in male patients or in blacks. The predominant causative organism varied with age. Overall, Haemophilus influenzae was the most common causative organism, but 32 percent of cases were due to Streptococcus pneumoniae. Case fatality rates were high for S. pneumoniae (12.5 percent) and very high for the small number of elderly patients suffering from bacterial meningitis. CONCLUSIONS: Significant declines have occurred in the last decade in the incidence of bacterial meningitis in children, particularly in those younger than 5 years, and in disease caused by H. influenzae and group B streptococcus. PMID- 1746299 TI - A rural-urban comparison of prehospital emergency medical services in Nebraska. AB - BACKGROUND: Provision of emergency medical services (EMS) in the rural United States presents a unique challenge. While rural and urban EMS outcomes have been compared, differing urban-rural population characteristics and roles for rural ambulance teams can confound such comparisons. METHODS: A year-long study of the prehospital EMS was conducted in rural Richardson County, Nebraska. Data were collected on the age, sex, and race of patients, response time, transport distance, medical problems encountered, and treatment rendered enroute. These data compared with those from an urban Lancaster County comparison group and statistical data from the Nebraska State Health Department. RESULTS: In the rural county, 70 percent of calls involved the elderly, whereas 38 percent of the urban calls and 36 percent of the Nebraska State calls involved the elderly. The rural ambulance service was more likely to provide for routine transfers, to involve patients with fractures and cardiorespiratory and neurologic problems, and twice as likely to result in hospital admission than was the urban ambulance service. The frequency with which advanced life support measures were applied in the rural area was similar to that in the urban area. The rural area response times were equivalent to the urban area response times after the rural area long-distance transfers were excluded. The location of service in the rural area was more likely to be the hospital or nursing home, whereas the urban location was more likely to be a home, on a highway, or in a public setting. CONCLUSIONS: Prehospital EMS in this rural location involved a predominantly elderly population with a large number of routine transfers linking the nursing home and community hospital. Further comparisons of rural and urban EMS outcomes should account for possible differences in type and severity of illness and type and location of service. PMID- 1746300 TI - The SAGE-PAGE trial: do family genograms make a difference? AB - BACKGROUND: Despite enthusiastic promotion of family genograms, the impact of routine use of this tool on clinical practice has not been systematically examined. The present study investigated whether doing a genogram, or having one available, makes physicians more sensitive to psychosocial issues or in other ways affects the physician-patient relationship or the process of clinical care. METHODS: In a randomized clinical trial, patients visiting 5 physicians at an academic family practice center (n = 189) received a physician-administered genogram (PAGE); a self-administered genogram (SAGE), which the patient completed before seeing the physician; or no genogram. A fourth (baseline) group was tested without genograms prior to the randomized trial. RESULTS: Analyses of patients' and physicians' postencounter questionnaires showed no impact of genograms on how physicians think about and deal with clinical problems or how patients view the encounter with their physicians. Compared with control groups, neither patient- nor physician-administered genograms increased the physician's (self-defined) understanding of the patient or the importance the physician attached to psychosocial issues in the case. A positive finding was that physicians considered genograms more relevant when they did them themselves. On the other hand, physician-administered genograms also increased the length of the encounter and were substantially less complete (conveying less information) than genograms completed by patients. CONCLUSIONS: THe results leave open the possibility that genograms do make a difference when used routinely by residents or experts or in difficult cases when family assessment is indicated. While enthusiasm about genogram applications in family medicine is understandable, the clinical utility of this tool remains to be demonstrated scientifically. PMID- 1746301 TI - Variations among family physicians' management strategies for lower urinary tract infection in women: a report from the Washington Family Physicians Collaborative Research Network. AB - BACKGROUND AND METHODS: This study surveyed a random sample of Washington State family physicians regarding their attitudes toward and usual practices in providing care to women with lower urinary tract infection. RESULTS: Based on a 70 percent response rate, wide variations in diagnostic testing, treatment, and follow-up strategies were identified. For example, a patient vignette presenting an uncomplicated infection prompted 82 separate management strategies among the 137 replies. Attitude questions also showed wide variations in spite of stated physician confidence and comfort in evaluating and managing urinary tract infection. Associated estimated costs ranged from negligible to more than $250 per case. CONCLUSIONS: These findings demonstrate significant physician variability in managing women's lower urinary tract infections. PMID- 1746302 TI - An approach to difficult management problems in otitis media in children. AB - BACKGROUND: Otitis media is one of the most common pediatric diseases encountered by family physicians. While isolated, acute episodes pose little clinical difficulty, recurrent infections and persistent middle ear effusions can be perplexing problems. METHODS: This review presents a clinical approach to the management of recurrent and persistent middle ear disease. RESULTS AND CONCLUSIONS: Recurrent infections can be treated with a trial of daily prophylactic antibiotics to decrease the rate of recurrence. Should infections continue to recur despite the daily prophylaxis, polyethylene tube placement is warranted to drain surgically the middle ear effusions that give rise to the recurrent infections. Acute episodes of otitis media are commonly followed by prolonged, asymptomatic periods of middle ear effusion. Patients with this disease have decreased hearing leading to potential deficits in their speech and academic development. If such effusions do not spontaneously resolve within 2 months, repeated courses of antibiotics with the possible addition of a course of oral steroids are warranted to speed resolution of the effusion before proceeding to placement of polyethylene tubes. PMID- 1746303 TI - Postpartum urinary retention. AB - BACKGROUND: Urinary retention is a common and frustrating complication in women during the immediate postpartum period. Physiologic changes in the bladder that occur during pregnancy predispose patients to develop symptomatic retention of urine during the first hours to days after delivery. METHODS: The incidence and characteristics of postpartum urinary retention were researched through a literature review and are illustrated by a case report. RESULTS AND CONCLUSIONS: Postpartum urinary retention has a reported incidence ranging from 1.7 to 17.9 percent. Factors associated with postpartum urinary retention include (1) first vaginal delivery, (2) epidural anesthesia, and (3) Cesarean section. Treatment begins with supportive measures to enhance the likelihood of micturition, such as ambulation, privacy, and a warm bath. If these measures are not successful, catheterization can be performed. If the bladder contains more than 700 mL of urine, prophylactic antibiotics may be warranted, because prolonged or repeated catheterization may be necessary. PMID- 1746304 TI - Cat-scratch disease associated with erythema nodosum. PMID- 1746305 TI - Transient cerebrospinal fluid rhinorrhea, blurred vision, and headache as presenting symptoms of pituitary adenoma. PMID- 1746306 TI - Penile fracture. PMID- 1746307 TI - Being there: on the place of the family physician. PMID- 1746308 TI - Current report--HIV. Counseling patients about HIV test results. PMID- 1746309 TI - Probing the mystery of clinical work. PMID- 1746310 TI - Outcomes research, patient preference, and the primary care physician. PMID- 1746311 TI - Toward reduction of neonatal mortality. PMID- 1746312 TI - Management of streptococcal pharyngitis. PMID- 1746313 TI - Cognition dysfunction. PMID- 1746314 TI - Preemployment evaluations. PMID- 1746315 TI - Release kinetics of ATP in cells exposed to nonionic detergents. AB - We have previously shown that the protein binding of intracellular ATP could be examined by monitoring the ATP release kinetics from Triton X-100 and Brij 58 nonionic detergent permeabilized cells. We have now analysed the protein binding of ATP in an isotonic medium using intact and partially ATP depleted Brij 58 treated human erythrocytes. The effects of Triton X-100 below the critical micelle concentration (CMC) was studied in normal and tumorous tissue culture cells and human red blood cells. Our results showed that the protein association of ATP was altered in the partially ATP depleted erythrocytes. Below the CMC value, but above a critical level Triton X-100 treatment was effective in mobilizing the intracellular ATP in both cell types. The ATP release curves were sigmoidal and an 'all or none' type of response was observed, especially in erythrocytes. The use of Triton X-100 (less than CMC) delays the detergent induced cell decomposition time thus providing a new approach to investigating the physical state of intracellular ATP. PMID- 1746316 TI - Green flavoprotein from P. leiognathi: purification, characterization and identification as the product of the lux G(N) gene. AB - A green flavoprotein (GFP) was isolated and purified to homogeneity from Photobacterium leiognathi, strain 208. GFP is a homodimer of molecular weight 54,000 and contains two molecules of an unusual flavin per molecule of protein. Various biochemical characteristics including isoelectric point, trypsin and chymotrypsin degradation, SDS and temperature influence on subunit dissociation and the dissociation of the flavin chromophore, were investigated. The sequence of 23 N-terminal amino acids was determined and found to be concurrent with the N terminal amino acid sequence encoded by the lux G(N) gene of P. leiognathi. This fact suggests that GFP is a structural component of the Photobacterium luminescence system. PMID- 1746317 TI - Expression and quantification of firefly luciferase under control of Rhizobium meliloti symbiotic promoters. AB - We have tested the use of firefly luciferase for monitoring regulated symbiotic nitrogen fixation gene expression. Broad-host-range plasmids carrying translational fusions of Rhizobium meliloti nifH, fixA and nifA promoters were constructed. Despite low levels of promoter activity the absence of Escherichia coli endogenous luminescence and the high sensitivity of the bioluminescent assay for firefly luciferase allowed rapid screening for functional luciferase expression. Plasmids containing symbiotic promoter-luc fusions were established in R. meliloti. Luciferase activity was detected and measured in both vegetative and symbiotic cells giving comparable results with those obtained by beta galactosidase assays. In addition, the luciferase assay was quicker, more sensitive and could be carried out with unrestricted cells. Furthermore, bioluminescence was high enough in alfalfa nodules containing nifH-luc fusion to be observed by a dark-adapted eye and photographed. PMID- 1746318 TI - Extra-weak chemiluminescence of drugs. XII. Effect of the molar ratio of amino acid to sugar on extra-weak chemiluminescence in the Maillard reaction. AB - The extra-weak chemiluminescence in the Maillard reaction caused by the reaction between L-lysine and D-arabinose was measured, and a linear relationship was found between the chemiluminescence and the amount of L-lysine added. After a 1 hour reaction equimolar amounts of D-arabinose and L-lysine were consumed regardless of the initial concentration of D-arabinose. The chemiluminescence of the Maillard reaction originates from Maillard reaction products formed by the equimolar reaction between sugar and amino acid and depends on the concentration of amino acid. PMID- 1746319 TI - Chemiluminescence intensities and spectra of luminol oxidation by sodium hypochlorite in the presence of hydrogen peroxide. AB - Hydrogen peroxide amplifies the chemiluminescence in the oxidation of luminol by sodium hypochlorite. A linear relationship between concentration of hydrogen peroxide and light intensity was found in the concentration range 5 x 10(-8)-7.5 x 10(-6) mol/l. At 7.5 x 10(-6) mol/l H2O2 the chemiluminescence is amplified 550 fold. The chemiluminescence spectra of these reactions have a wavelength maximum at 431 nm independent of the concentration of hydrogen peroxide. The results indicate that hydrogen peroxide is a necessary component in the chemiluminescent oxidation of the luminol by sodium hypochlorite. PMID- 1746320 TI - Bioluminescence and chemiluminescence literature. The 1990 literature: Part I. PMID- 1746321 TI - Hydration phenomena: an update and implications for the food processing industry. AB - The past decade has witnessed major revisions in our perception of the manner in which water affects the physical, chemical, and microbiological attributes of all manner of food-related systems. The growing realization that, during processing, most such systems are brought to, and maintained in, a state of thermodynamic instability is focussing attention on the dynamics of the various components in such systems. Older, equilibrium-based concepts, such as "water activity," equilibrium moisture sorption, and "bound" water are being discarded in favour of more appropriate descriptions, in terms of diffusion, nucleation, crystallization and relaxation rates, glass/rubber transitions, and steady states. It is being realized that food processing, materials science, and polymer technology have much in common, with water being the universal plasticizer of naturally occurring organic materials which form the basis of food products. PMID- 1746322 TI - Water relationships in foods. Advances in the 1980s and trends for the 1990s. 197th National Meeting of the American Chemical Society in Dallas, Texas, April 10-14, 1989. PMID- 1746323 TI - Studies of reaction kinetics in relation to the Tg' of polymers in frozen model systems. AB - The rates of diffusion-controlled processes in a frozen system can be influenced by the presence of glassy states. One characteristic of cryostabilization by this mechanism is a change in the temperature dependence of reaction rates at the Tg' of the system. The cryostabilization behavior of solutes such as maltodextrin, carboxymethylcellulose (CMC), and sucrose was studied. Three different model reaction systems (enzyme hydrolysis, protein aggregation, and non-enzymatic oxidation) were used. Maltodextrin had a consistent pattern of cryostabilization behavior at temperatures ranging from -3 degrees C to -20 degrees C for all three model systems. Significant retardation effects were evident in the temperature range corresponding to its glassy states. Sucrose did not show a stabilizing effect in the non-proteinaceous model system (the non-enzymatic oxidation reaction). This could partly be due to the absence of the glassy state, since the storage temperatures were above its Tg'. However, in the protein aggregation model system, sucrose was an excellent stabilizer in protecting actomyosin from aggregation. This may be explained by a "solute exclusion" mechanism. CMC did not show any stabilizing effect in the protein aggregation and non-enzymatic oxidation model systems studied, even though it has a Tg' as high as that of maltodextrin. These results demonstrated that although the presence of a glassy state may well have a retarding effect on the rates of diffusion processes, just knowing the Tg' of a polymer is not sufficient for prediction of its stabilization effect in a frozen system. PMID- 1746324 TI - DSC studies and stability of frozen foods. AB - This paper discusses the role played by the "WLF decrease in viscosity" above the temperature of the glass transition (Tg) in the temperature dependence of the stability of frozen foods. In the first part, the complex features observed before the melting endotherm on DSC/DTA thermograms of sugar-water solutions are examined; they are suggested to be representative of a glass transition associated with enthalpy relaxation. In the second part, the values of Tg for some complex foods are discussed. It is shown that ice melting adds an important contribution to the WLF effect on the decrease of the viscosity of the freeze concentrated phase. The temperature dependence of the deterioration processes observed in frozen food products is generally smaller than that expected from this viscosity decrease. Several hypotheses are presented to account for the discrepancy. PMID- 1746325 TI - Effects of water on diffusion in food systems. AB - A number of operations in food processing, and the stability of stored foods, are affected by diffusional properties of food systems, which include the foods themselves, their immediate environment within a package, and any barriers (packaging or coating) used with the foods. Water content and "water activity" affect these diffusional properties dramatically, by plasticizing food and/or packaging polymers and affecting glass transition temperatures of components, and in some cases, water may serve as an internal transport medium. The present paper reviews the current state of knowledge of effects of water on diffusion in food systems, and in particular, changes in diffusivity above glass transition temperatures. The complexity of resultant effects on food stability in dry and frozen foods is discussed. Examples of potential effects of glass transitions on stability of frozen foods are provided by computer simulation of shelf life using specified assumptions. PMID- 1746326 TI - Calorimetric and thermodielectrical measurements of water interactions with some food materials. AB - A new thermoanalytical method, which allows the measurement of complex dielectrical permittivities as a function of temperature in the microwave frequency domain, is described and compared to Differential Scanning Calorimetry (DSC) with respect to the characterization of water in food materials. Ice crystallization temperatures and melting enthalpies, measured by DSC dynamically on the same sample, allowed precise determination of the amount of frozen water and its enthalpy as a function of total water content, especially at low water contents near the unfrozen water limit. Thermal and Dielectrical Analysis (TDA) measurements provide immediate information about water interactions in food materials, even down to the lowest water contents, which are generally difficult to assess by other techniques. Dielectrical behaviour of eight glucose-water melts, containing from 0 to 24% water, has been examined as a function of temperature. The dependence of the observed dielectric relaxations on water content and temperature are discussed, and the results obtained by TDA are compared to those from conventional frequency sweeping determinations. The influence of temperature, hydration, and state of the material on dielectrical relaxation determinations are also discussed, with reference to glucose and sorbitol behaviour. The variations in dielectric constant during starch heating and dehydration are presented and analysed, with the aim of understanding the microwave drying process. PMID- 1746327 TI - Effect of solute on the nucleation and propagation of ice. AB - Using the emulsion technique, we have studied nucleation of ice in aqueous solutions containing silver iodide or Pseudomonas syringae. Using a Differential Scanning Calorimeter (DSC), we determined characteristic temperatures of nucleation, and also rates of nucleation at selected temperatures. The freezing point depression induced by added solute is linearly related to the lowering of both homogeneous and heterogeneous nucleation temperature. Nucleation kinetics depend on a fifth power function of the temperature. Solute is found to affect the parameters of this relationship in different ways, dependent upon the nature of the catalytic site for ice nucleation. We have also studied the effect of composition on the linear propagation velocity (LPV) of ice in undercooled solutions contained in a U-tube. We have determined velocities in a range of concentrations of sugar solution at the same undercooling, and also as a function of undercooling. The role of added polymer has also been investigated. It is affected by the sugar concentration. PMID- 1746328 TI - Thermal analysis of water-containing systems. AB - Thermal analytical techniques offer many advantages in investigations of water containing systems. This paper will review some of the methodologies used by us in studying food systems: 1) Differential Scanning Calorimetry (DSC): for determining freezable water, melting point, Tg' (see text), etc. 2) ThermoMechanical Analysis (TMA): for determining softening points as a function of water content, dilatometry and glass transition temperatures. 3) ThermoGravimetric Analysis (TGA): for investigating water uptake curves and water content determination. 4) Dynamic Mechanical Analysis (DMA): for the determination of low-energy transitions. PMID- 1746329 TI - Food-water relations: progress and integration, comments and thoughts. PMID- 1746330 TI - Thermomechanical analysis of frozen aqueous systems. AB - Thermomechanical Analysis (TMA), using the parallel-plate-rheometer mode of the DuPont 943 TMA, was used to evaluate the softening properties of frozen aqueous carbohydrate model systems. A sample (of fixed dimension) of frozen solution was placed between the parallel plates and cooled to -80 degrees C. The sample was then heated at a linear heating rate of 2 degrees C/min to +15 degrees C. The dimension change was plotted as a function of temperature or time, and an estimate was made of the glass transition point and of the thermal softening behavior of the system. Good agreement was found with previously published glass transition data for similar frozen carbohydrate model systems measured by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). PMID- 1746331 TI - Vitreous domains in an aqueous ribose solution. AB - Aqueous solutions containing d-ribose demonstrate the ability to form more than one vitreous domain when exposed to low temperatures. Differential scanning calorimetry revealed two glass transitions (at Tgs of -63 and -43 degrees C) upon cooling and warming at a constant rate of 5 degrees C.min-1. The bulk water of the solution crystallizes at -18 degrees C (Tc). Heat capacity and enthalpy changes, and the derivatives for each thermal event, are calculated. Relaxation studies on the observed Tgs produced anticipated overshoots characteristic of the presence of glassy states. PMID- 1746332 TI - Effect of sugars and polyols on water in agarose gels. AB - Effects of ribose, glucose, sucrose, ethylene glycol, glycerin, propylene glycol, and sorbitol on water in concentrated agarose gels were studied by differential scanning calorimetry at low temperatures. Changes in the phase transition temperatures of 40% agarose gels, induced by the addition of these chemical reagents, are discussed, together with rheological and thermal data for the same systems at ambient and higher temperatures. Both sugars and polyols are believed to reduce the amount of freezable water and to promote plasticization and molecular mobility of agarose chains in gels, thus shifting the glass transition temperatures to lower temperatures. However, the effects of decreasing freezable water, and the direct effect on the junction zones, produced by sugars seem to be different from the effects produced by polyols. PMID- 1746333 TI - Non-equilibrium phase transitions of aqueous starch systems. AB - Experimental data on phase transitions of aqueous starch systems, obtained by thermal analysis (TA) methods, are often indicative of irreversible (non equilibrium) processes involving various metastable states. The thermal responses usually reflect composite effects from contributions of several opposing processes [e.g. annealing, melting, and (re)crystallization] taking place concurrently during TA. It is important, therefore, to recognize the temperature- and time-dependence of the structure of starch materials, if non-isothermal techniques are used for their characterization. Identifying the pertinent morphological features (supermolecular structure) of each particular system, as well as recognizing the role of water as a plasticizer which depresses the Tg of the amorphous domains, is essential to predict heat/moisture-mediated transformations of this biopolymer. The phase transition behaviour of granular starch and amylose-lipid complexes, as revealed by Differential Scanning Calorimetry and Thermomechanical Analysis, and the metastability of these materials are considered herein with respect to the effects of water and low molecular weight solutes. PMID- 1746334 TI - Mechanism of misoprostol stabilization in hydroxypropyl methylcellulose. AB - The stability of misoprostol oil is significantly improved in a hydroxypropyl methylcellulose (HPMC) dispersion (1:100). In order to understand the enhanced stability of misoprostol oil in HPMC, the physical state of misoprostol oil in HPMC films was investigated using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and transmission IR (TIR). Further, to determine the effect of polymer structure and the mobility of both water and misoprostol on misoprostol stability, the rate of misoprostol degradation was investigated in the misoprostol/HPMC dispersion (1:100) at 55 degrees C. The water sorption isotherm of the dispersion at 55 degrees C was determined, at seven different relative humidities, ranging from zero to 81%. The DSC and DMA measurements indicated that misoprostol oil, up to 29% in dry weight, is molecularly dispersed in the glassy HPMC. The TIR studies showed no evidence of complexation between misoprostol and HPMC. Stability studies of the misoprostol/HPMC (1:100) dispersion indicated that the first-order rate constants for misoprostol degradation increased in a concave-up fashion as the water content of the dispersion increased. Below two percent water content, the rate of misoprostol degradation was found to be minimal. Overall, it is suggested that misoprostol is stabilized in the dispersion by being molecularly dispersed in HPMC. Further, the glassy state of HPMC should reduce the mobility of misoprostol and water, leading to a minimal rate of degradation for misoprostol at low moisture levels. PMID- 1746335 TI - A food polymer science approach to structure-property relationships in aqueous food systems: non-equilibrium behavior of carbohydrate-water systems. AB - Descriptions of the functional significance of carbohydrates based on the familiar equilibrium thermodynamics of very dilute solutions fail for pragmatical time scales and conditions, which are far from equilibrium. This is not too surprising, since limiting partial-molar properties reflect the independent behavior of solute in the limit of infinite dilution where free volume is maximum at a given temperature, while Tg'-Wg' properties reflect the cooperative behavior of solute-plasticizer blends at the limiting minimum value of free volume to observe relaxation within experimental time scales. Carbohydrate-water systems, with well-characterized structure and MW above and below the entanglement limit, provide a unique framework for the investigation of non-equilibrium behavior. Thermal analysis by DSC reveals the central role of water as a plasticizer for carbohydrates and of the glass transition as a physicochemical parameter that governs their properties, processing, and stability. A classical polymer science approach is used to study structure-property relationships of carbohydrates as water-compatible food polymers, which are treated as homologous systems of polymers, oligomers, and monomers with their plasticizers and solvents. Mechanical relaxation behavior is described by a "transformation map" of the critical variables of moisture content, temperature, and time. The glass curve is a reference contour, which represents the limiting isogram for free volume, local viscosity, relaxation rates, and rotational and translational mobility. Map domains are discussed as aspects of "water dynamics," to dispel the myth of "bound water," and "glass dynamics," to relate to macroscopic structure and collapse phenomena. A particular glass with invariant composition and Tg (prepared by freeze-concentration) is identified as a pivotal and practical reference state. The Tg observed during DSC analysis is often an effective Tg, resulting from instantaneous relative relaxation rates and non-uniform distribution of total sample moisture. Non-equilibrium melting, annealing, and gelation/recrystallization of kinetically metastable, partially crystalline carbohydrate systems exhibit non-Arrhenius kinetics which depend on the magnitude of delta T above the appropriate Tg, as defined by WLF relaxation transformations. Thermally reversible aqueous gels (crystallized from an under cooled, rubbery melt) are described by a "fringed micelle" structural model for a three-dimensional polymer network, composed of microcrystalline junction zones crosslinking plasticized amorphous regions of flexible-coiled, entangled chain segments. PMID- 1746336 TI - The prediction of water activities in multicomponent systems. AB - The molecular bases of the equilibrium water activity concept are discussed and illustrated using some simplified examples. It is shown, using a relatively refined treatment, that at the moment we are not in a position to predict water activities, even for simple systems. A method is described which allows the prediction of the water activity of multicomponent systems from the properties of solutions containing one and two solutes. The method can also be used to predict solubilities in systems containing more than one solute, and this is illustrated with an example. PMID- 1746337 TI - Trends in research related to the influence of "water activity" on microorganisms in food. AB - The use of humectants and drying to make foods safe and stable has been one of the underlying principles of food preservation for centuries. With the more recent discovery that the ratio of water vapor pressure to that of pure water (aw) is a useful parameter when related to microbial growth and other stabilizing factors in foods, a valuable means of predicting stability factors based on water limitation has become available. Microorganisms have been categorized with respect to their capacity to grow and produce metabolites in various conditions of limited aw. In addition, the metabolic basis for microbial inhibition has now been determined and schemes for its genetic control have been uncovered. The implications that these discoveries have in a wide variety of applications are far-reaching. PMID- 1746338 TI - Effects of order of mixing and solute interactions on the "water activity" of concentrated solutions. AB - Experimental results indicate that order-of-mixing effects in concentrated sugar salt solutions are functions of salt:sugar concentrations, types of sugars and salts, time after mixing of clear solutions, and solute interactions. Visual clarity of the solutions after preparation and at least 16 hours of storage may not be a sufficient indicator of complete solvation. The order of mixing solutes may cause differences in their rates of hydration, resulting in differences in "Aw" at non-equilibrium conditions, whereas Aw is only meaningful at thermodynamic equilibrium. Determining a thermodynamic equilibrium Aw in diffusion-resistant foods may take much more time and be more difficult to measure than in the solutions reported in this paper. PMID- 1746339 TI - Aspartame degradation as a function of "water activity". AB - The incorporation of aspartame into an increasing number of foods necessitates evaluation of its degradation kinetics as a function of "water activity" (aw). The kinetics of degradation were followed in model systems as a function of initial pH, temperature, and aw. An increase in aw, for each 0.1 units in the 0.3 to 0.7 range, resulted in about a 30-80% increase in degradation rate, which then decreased only slowly up to dilute solution. The presence of oil increased the degradation rate at high aw, but glucose had no effect on the rate of aspartame loss. The activation energies for loss ranged from 25 to 20 kcal/mole, decreasing as aw increased, as expected. The rates as a function of pH showed that the actual pH of the water in the condensed phase, based on the Bronsted relationship, may be very different than the initial pH. This caused a shift in the pH at which the fastest rate of degradation occurred, as aw increased. PMID- 1746340 TI - Volume effects of starch-water interactions. AB - Volume changes arising from the sorption of water by three starches have been determined by dilatometry. By a recently described method, parameters of the G.A.B. equation have been used to resolve the volume changes into contributions from strongly sorbed water molecules in contact with the surface and from weakly sorbed water molecules in the remaining water layers. The latter produced only small volume effects. In contrast, the contact sorption caused very large volume decreases. Changes in these decreases with changing water content indicated two types of sorption sites, possibly crystalline and amorphous. In the case of waxy maize starch, for which literature data concerning its degree of crystallinity were available, the contact sorption could be quantitatively resolved into contributions from the presumably crystalline and amorphous portions, with the former exhibiting both higher affinity and larger volume changes for water molecules than the latter. PMID- 1746341 TI - Water diffusivity in starch-based systems. AB - The objective of this study was to investigate the influence of structure, and component interactions, on the sorption and transport properties of water in starch-based systems. We compared the effective diffusivity (Deff) of water in two starches, with differing amylose-amylopectin ratios, using either kinetics of water adsorption or analysis of drying curves (water desorption) to estimate Deff. The effect of incorporating small sugar molecules into the granular or gelatinized starch matrices on Deff was measured by drying curve analysis. To investigate the possible mechanisms of water transport, the porosity and microscopic appearance of the samples at different stages of drying were determined. In a complementary study, sorption isotherms and the number of accessible "binding" sites in the starch and starch-sugar systems were determined using gravimetric analysis and inverse gas chromatography (IGC) 'probe analysis'. In the case of the starch-sugar systems, the measurements were made after the components had been 'mechanically mixed', or after more intimate mixing had been achieved by a co-freeze-drying process. The Deff of the starches was found to depend, in a complex way, on the moisture content of the samples. At relatively high moisture contents, the predominant mode of water transport was by liquid diffusion. As the samples became drier, their porosity increased, and the predominant mode of moisture transport was by vapor phase diffusion. As the samples became very dry (less than 10% water content), Deff fell significantly. Incorporation of sugars, in general, led to a reduction of Deff, which was correlated with a corresponding fall in porosity. In agreement with the findings of other workers, for the starches studied, the value of Deff determined from water adsorption measurements was significantly less than Deff determined from water desorption (drying curve analysis). The form of the Deff versus moisture content relationship was, however, independent of the method of measurement (adsorption or desorption). The water sorption and IGC probe analysis results indicated that some physicochemical interaction was expedited by the freeze drying process. This interaction was manifested by a reduction in water sorption at a given relative vapor pressure, and by major changes in the accessibility of the co-freeze-dried samples to organic probe molecules. Taken together, the results indicate that water transport (diffusion) in starches and in starch-sugar mixtures is dependent significantly on gross structural features (development of porosity during drying), but that specific molecular, physico-chemical interactions must also be considered. PMID- 1746342 TI - Kinetics of water sorption in packaging materials for food. AB - The water content of paper and its time dependence are of great importance for the use of paper and cardboard as packaging materials. The physical process of water sorption and the mechanisms of water "binding" in paper, as fundamental principles of the kinetics, are discussed. Water exists in up to four different "states" (i.e. domains of mobility) in paper: the first layer at the primary sites on the surface of the fibers; the multimolecular layers, with less "binding" energy, on these inner surfaces; condensed water in the voids; and dissolved water in the cellulose fibers. All these "states" influence the shape of the sorption isotherm and correspond to a different water content and to different transport mechanisms. The various types of water "binding" on paper were studied by measuring the transversal relaxation rate, T2, using a pulsed Nuclear Magnetic Resonance spectrometer (minispec pc 120). In addition, a non destructive, fast method of determining the water content in packaging materials with NMR spectroscopy is described. PMID- 1746343 TI - Use of NMR and MRI to study water relations in foods. AB - Water is the most important component of a food system, because it influences so many process variables, product characteristics, and stability attributes. Some of the most successful techniques used to probe the behavior of water in food systems are Nuclear Magnetic Resonance (NMR) spectroscopy and, more recently, pulsed-field gradient NMR and Magnetic Resonance Imaging (MRI). The purpose of this chapter is to review the theory underlying these techniques and to present several examples of how they have been applied to study water relations in foods. PMID- 1746344 TI - The effect of mechanical deformation on the movement of water in foods. AB - This study has shown the importance of relating NMR spectroscopic information on the water in model food structures to the mechanical properties of those structures. Analysis of the NMR relaxation data can be used to examine the distribution of water domain sizes, and this has been related to the mechanical properties of the samples. A novel NMR probe-head has been designed, which allows both the NMR and the mechanical data to be simultaneously measured during compression of the sample. This probe-head allows compressive stress/strain data to be obtained directly from the NMR sample, allowing changes in the distribution of the water to be directly correlated to changes in mechanical properties. PMID- 1746345 TI - Molecular behavior of water in a flour-water baked model system. AB - The molecular behavior of water in complex food systems, via bonding and solvation reactions with low molecular weight solutes or high molecular weight macromolecules, is intimately linked with both the palatability and storage stability of those systems. Due to the difficulty in interpreting data derived from multicomponent finished food products, water behavior in a baked flour-water "matzo" model system was studied. Water behavior was assessed from high resolution [1H] nuclear magnetic resonance (NMR) spin-spin relaxation studies and differential scanning calorimetric (DSC) measurements of unfreezable water content. The unfreezable water capacity of "matzo" model crackers, as measured by DSC, ranged from ca. 24-30% (w/w). These results were corroborated by NMR data. Only one exponent (less than 0.46 msec greater than) is required to fit spin-echo evolution curves below a total moisture content of ca. 20% (w/w), whereas two exponents (less than 0.46 greater than and 1.6 msec) are observed when the moisture content exceeds 20% (w/w). Expert sensory texture assessments parallel unfreezable (= total) water contents between 2.9% (w/w) and 20.1% (w/w). This relationship may be explained by the known tendency for water to plasticize biological polymers, e.g. wheat starch and proteins, and to render these macromolecules incrementally more mobile with increasing water concentration. The similarities (if any) between water of plasticization, immobile water, and "bound" water are discussed, in terms of theoretical physicochemical "states" of water and the various techniques utilized to assess (define) those "states." PMID- 1746346 TI - 1H and 2H NMR studies of water in work-free wheat flour doughs. AB - Proton and deuterium NMR relaxation methods were used to characterize water compartmentalization and hydration in work-free wheat flour doughs. Transverse (spin-spin) relaxation measurements define three motionally unique water compartments in the work-free dough preparations. The apparent occupancy fraction and relative mobility of each water domain are found to be functions of moisture content, temperature, and flour type. Additionally, the number of relaxation resolved water compartments and their characteristic relaxation rate constants are found to depend critically on both moisture content and the interpulse-delay employed for the multi-pulse relaxation experiments. Under controlled experimental conditions, dynamics between the three water compartments can be observed to be consistent with the onset of flour hydration. The most notable observation during the initial period of hydration is a loss of "free" or "loosely bound" water to environments characterized by less mobility. Freezing studies show that hard wheat doughs have slightly less amorphous, non-freezable water than do soft wheat flour doughs prepared under similar conditions. PMID- 1746347 TI - Magic-angle 13C NMR analysis of hard wheat flour and dough. AB - Samples of hard wheat flour and dough are analyzed by magic-angle spinning 13C NMR spectroscopy. Cross-polarization magic-angle spinning (CPMAS) 13C NMR spectra of the dry flour allow its starch and protein content to be accurately measured. These two components are phase-separated. Spectra of hydrated hard wheat doughs are collected under both CPMAS and single-pulse carbon with low-power 1H decoupling conditions. The former report on the macromolecular components of the dough, while the latter reveal small molecules which are solubilized by the water. Results of the present study are interpreted as indicating that the protein is largely unaffected by the added water and remains phased-separated from the starch, while water causes significant changes in polymer dynamics of the starch component. PMID- 1746348 TI - Molecular dynamics of water in foods and related model systems: multinuclear spin relaxation studies and comparison with theoretical calculations. AB - A review of recent studies of molecular dynamics of water in foods and model systems is presented, and the theoretical results are compared with experimental data obtained by several techniques. Both theoretical and experimental approaches are discussed for electrolytes, carbohydrates, and food proteins in solution. Theoretical results from Monte Carlo simulations are compared with experimental NMR relaxation data for quadrupolar nuclei such as those of deuterium and oxygen 17. Hydration studies of wheat, soybean, corn, and myofibrillar proteins by multinuclear spin relaxation techniques are discussed, and several new approaches to the analysis of the experimental data are considered. Correlation times of water motions in hydrated food systems are determined from NMR and dielectric relaxation data. The values of the correlation times for dilute solutions of electrolytes and carbohydrates estimated by NMR are in good agreement with those calculated from dielectric relaxation data, but seem to differ significantly from those proposed from Monte Carlo simulations. Several new and important results concerning the hydration of potato and cereal starches are presented, showing the very different hydration behaviors of these two major groups of starches. The combination of molecular dynamics computations with NMR relaxation techniques will hopefully stimulate novel technological developments in food engineering based on such fundamental studies. PMID- 1746349 TI - Protein-water interactions from 2H NMR relaxation studies: influence of hydrophilic, hydrophobic, and electrostatic interactions. AB - The importance of water interactions with proteins in food systems is well documented. A controversy exists, however, as to the nature of these interactions and the effect of protein structural changes on them. To clarify these questions, a method has been developed for determining hydration from the protein concentration-dependence of deuteron resonance relaxation rates. Measurements were made in D2O on beta-lactoglobulin A to study effects of hydrophilic interactions, and on both casein micelles and submicelles to study hydrophobic and electrostatic effects. From the protein concentration-dependent relaxation rates, the second viral coefficients of the proteins were obtained by nonlinear regression analysis. Using either an isotropic tumbling or an intermediate asymmetry model, hydrations, upsilon, and correlation times, tau c, were calculated for the protein-associated water; from tau c, the Stokes radius, R, was obtained. Variations in upsilon and R were in accord with known structural changes in molecular states of the proteins. The NMR results are compared with hydrations and structural information derived independently from small-angle X ray scattering. PMID- 1746350 TI - Solute-polymer-water interactions and their manifestations. AB - This paper reviews recent work on the interactions among solutes, polymers, and water in model food systems. Four possible combinations of ionic or non-ionic solutes and polymers are discussed in terms of their water sorption behavior. Comparisons between experimental values and values calculated by a mass balance equation are made. The salt-protein, sucrose-starch, and salt-starch combinations sorbed less water than that predicted by calculated sorption values. This was attributed to the inability of the interacted solutes to sorb their full complement of water. On the other hand, the sucrose-protein combination exhibited an increase in the amount of water sorbed over that calculated by the mass balance equation. This was attributed to the increased hydration of the protein component, due to an effect of the sucrose. One of the major factors involved in these solute-polymer interactions is the competition for water among the solutes and polymers. This competition, in turn, is greatly influenced by the "state" of the water associated with these components. Lastly, examples of how biological, chemical, and physico-chemical phenomena in foods are affected by these factors are also given. The phenomena discussed include mold germination, the Maillard reaction, ascorbic acid oxidation, protein functionality, starch gelatinization and retrogradation, and the complication of the order of mixing. PMID- 1746351 TI - Deuterium nuclear magnetic resonance studies of potato starch hydration. AB - Deuterium Nuclear Magnetic Resonance (NMR) measurements at 4.7 Tesla were used to study the hydration properties of potato starch suspensions as a function of the starch-to-water ratio. The deuterium NMR spectrum of potato starch suspensions consisted of a relatively tall, single Lorentzian (D2O) peak and a resolved doublet ('powder' pattern) of about 1 kHz quadrupole splitting and low amplitude. The deuterium NMR transverse relaxation rate (R*2) was measured for the single Lorentzian, deuterium oxide peak; this rate increased with increasing starch-to water ratio. Deviations of such R*2 dependences from linearity were observed only at high ratios of starch-to-water, above approximately 40% solids. In addition to the 'free' or bulk population (which has a very fast rotational correlation time of 5 ps), a second population of water weakly sorbed on the starch granule surface was monitored and found to be in fast exchange with the bulk water; this second water population has a rotational correlation time of 17 ps at 298 K, only about three times slower than that of bulk water. Additionally, a third population of slowly exchangeable water is present, which is "anisotropically bound" and has a highly restricted motion within the potato starch granule structure; well-defined quadrupole splittings are observed from this latter population of water in potato starch. Potato starch exhibits unique hydration properties that have not been found in cereal starches. PMID- 1746352 TI - Determination of moisture content by pulsed nuclear magnetic resonance spectroscopy. AB - Water is vital to all life processes. In foods, water is often the key component which determines the extent and rate of several chemical reactions, as well as the growth of microorganisms. There are several methods available to measure water content in foods; however, one of the most successful methods is Nuclear Magnetic Resonance (NMR) spectroscopy. The NMR method is rapid and accurate and, most importantly, non-destructive to the sample. The purpose of this chapter is to discuss the use of NMR, both as a research tool and as a quality control (off- and on-line) method, to measure moisture content in food components and food systems. PMID- 1746353 TI - Phase volume measurements using magnetic resonance imaging. AB - The phase distribution of components in both model and actual food systems has been quantified using Magnetic Resonance Imaging. We present measurements of effective moisture diffusivities, vertical mass distributions in foams, and crystallization of water and lipid components. The interpretation of this information allows one to quantify the interactions of various components and structural features within a sample. These measurements are made noninvasively and nondestructively and can be repeated over time to obtain information on the dynamics of the system. PMID- 1746354 TI - Thermoplastic starch. PMID- 1746355 TI - Crystallization from concentrated sucrose solutions. AB - When concentrated aqueous solutions of sucrose are cooled, ice or sucrose crystals separate, depending on the concentration and temperature. The state diagram of the sucrose-water system describes both the equilibrium and non equilibrium behaviour. A detailed account is given of the effect of sucrose concentration and various, principally polysaccharide, stabilizers on the processes of homogeneous and heterogeneous nucleation, as well as the kinetics of crystal growth. Increasing concentrations of sucrose reduce the diffusion coefficient of water molecules and the linear growth velocity of ice crystals. Polysaccharide stabilizers have relatively little effect until incipient gelation occurs. Thereafter, there is a gross change in crystal form and growth rate. A careful analysis of the impact of sucrose concentration on the rate of ice crystal growth has not permitted satisfactory matching of theoretical predictions with actual behaviour. Recent studies of the rate of growth of sucrose crystals in sucrose glasses of varying water contents are recorded. There is no simple relationship between the moisture content (in the 2-12 w/w % H2O range) and the rate of growth of the sucrose crystals. PMID- 1746356 TI - Wheat gluten: rheological and gas retaining properties. AB - Three general properties of the gluten proteins appear to be responsible for gluten's ability to product unique light products. First is the ability to form a cohesive dough. This probably results from the low charge density of the proteins, which allows for strong hydrogen and hydrophobic bonding. The second factor is the ability of the dough to retain gas. This appears to result from the slow diffusion of low molecular weight molecules, including carbon dioxide, through the gluten matrix. The third factor is the transformation of dough to bread. Little is known about this transformation. PMID- 1746357 TI - Leaching of amylose from wheat and corn starch. AB - Wheat starch gave a 21% yield (based on starch) of amylose (AM) when leached at 3% solids under mild agitation, and at a heating rate of 10 degrees C/min to 95 degrees C followed by holding at least 10 min. Annealing wheat starch prior to leaching at 95 degrees C or using a heating rate of 1 degrees C/min during leaching, increased AM yield from 21% to 23% at 3.0% starch solids, and 8% to 16% at 4.5% starch solids. At 0.5% solids, almost all wheat AM (29% of starch) was solubilized into the continuous phase at 95 degrees C, but only one-half of the lipid in the starch co-leached with AM. Corn starch behaved similarly to wheat starch during leaching below 1.5% starch solids, while at 3.0% almost 40% more AM was obtained from wheat than corn starch. Wheat AM molecules isolated by leaching were larger than those obtained by crystallizing its n-butanol complex, and they gave a different size-distribution as evidenced by high-performance size exclusion chromatography. A triangular phase diagram was useful in depicting the overall process of leaching AM from starch. The critical concentrations of wheat (5.4%) and corn (5.2%) starches were determined using phase diagrams. PMID- 1746358 TI - Ionic diffusion in frozen starch gels. AB - Quality changes in food frozen by different conditions and at different storage temperatures were demonstrated using a model system. A frozen starch gel represents a frozen food matrix, and ions in the external medium represent the reactant molecules. We determined the effective diffusion rates of Zn+2 ions into frozen starch gel cylinders that were frozen at different freezing rates. The diffusion was performed at -8 degrees and -15 degrees C. The amounts of ion diffused were determined by atomic absorption, whilst the structure of the frozen samples could be simultaneously determined by scanning electron microscopy. The effective diffusion rates were found to correlate with the amount of unfrozen portion of the samples. This suggests that ions move mainly through the unfrozen portion around the ice crystals. Fast- and slow-frozen samples exhibited significantly different effective diffusion rates at -15 degrees C, which might be due to differences in size and orientation of ice crystals. Zn+2 ions moved slower at -15 degrees C than at -8 degrees C. PMID- 1746359 TI - Resistance of lipid films to transmission of water vapor and oxygen. AB - Various lipids, present as thin films on polar filter paper supports, were evaluated for resistance to the transmission of water vapor (rH2O) and oxygen (rO2). Beeswax exhibited the largest r(H2O), followed in order by fully hydrogenated soy-rapeseed oil, stearyl alcohol, acetylated monoglycerides, hexatriacontane, tristearin, and stearic acid. Most of the lipids exhibited negative activation energies, E, for resistance to transmission of water vapor and positive Es for resistance to transmission of oxygen. The type of lipid support (hydrophobic or hydrophilic) also influenced E for resistance to water vapor transmission. Differences in r(H2O) for the various lipids, comparative r(H2O) and r(O2) values, and the temperature dependence of these values can be explained, in part, by the degree of hydrophilicity of the lipid molecule. Tempering at 48 degrees C of stearyl alcohol caused a substantial decrease in its permeability to oxygen and water vapor. The polymorphic form of a blend of fully hydrogenated soybean and rapeseed oil had a moderate influence on its permeability to oxygen and water vapor. This information will be useful for formulating lipid-containing films with controlled barrier properties to the passage of water vapor and oxygen. PMID- 1746360 TI - Compression of foods during freeze-drying: water plasticization at the ice-dry layer interface. AB - The compressive mechanical properties of freeze-dried green beans show a pronounced decrease in rigidity when moisture content and/or temperature are increased. There exist several temperature and moisture combinations which give common values for mechanical properties. These combinations also give a common compressive behavior. Using this information on mechanical properties, it is possible to predict a stress-strain relationship, if given either a temperature, a moisture content, or the value of a pertinent mechanical property. It is shown that the moisture contents and temperatures that exist in the dry layer during freeze-drying result in mechanical properties that are suitable for compression of the dry layer. From studies on compression behavior during freeze-drying, it is shown that applied compressive pressure is the main determinant of final degree of compression. Increasing the compressive pressure gave a higher compression effect and gave a more rapid drying, presumably due to improved heat transfer in the compressed dry layer. From the above information, a simple method to predict compression behavior during freeze-drying was developed. PMID- 1746361 TI - Molecular dynamics simulation of the aqueous solvation of sugars. AB - Recently, several molecular dynamics simulations of the aqueous solvation of carbohydrates have been reported. These studies represent the first theoretical picture available of the microscopic character of sugar solutions, and may provide explanations of the unusual and complex behavior of this class of molecules in solution. This paper will discuss two MD simulations of D glucopyranose, including a free energy perturbation calculation of the anomeric free energy difference. Solvation was found to have little effect upon the mean conformational structure of the pyranoid rings, but the presence of solvent significantly affected the motions and orientations of the exocyclic groups. Adjacent functional groups of the sugar rings were found to mutually perturb one another's hydration, depending upon the local stereochemistry, which may prove to play a part in the observed anomeric preferences of the sugars. From a component analysis of the free energy of solvation of the two anomers of D-glucopyranose, it was found that a large solvation term favors the beta anomer, which is the form found to be preferred in aqueous solution. PMID- 1746362 TI - Flexibility of globular proteins in water as revealed by compressibility. AB - In order to elucidate the flexibility-structure-function relationships of proteins, the adiabatic compressibility of about 30 globular proteins, including food proteins, was determined by means of sound velocity and density measurements in aqueous solutions. Most proteins studied showed positive compressibility, indicating the large internal flexibility of the molecules. The volume fluctuation was in the range of 30-200 ml/mol, which corresponded to about 0.3% of the total protein volume. From the statistical analyses of the compressibility data, it was found that the flexibility of proteins is closely related to structural factors such as hydrophobicity, helix element, and amino acid composition, and to functional properties such as digestibility and foaming capacity. These results indicate that the dynamics of protein structure should be taken into account in predicting precisely the functions and properties of a protein from its primary or tertiary structure. PMID- 1746363 TI - Interactions of ordered water and cations in the gel-forming polysaccharide gellan gum. AB - Gellan gum, useful to the food industry, is chosen as a model system for the investigation of the structural role of water molecules and cations in its gel forming properties. X-ray fiber diffraction technique has been used to determine the crystal structure of potassium gellan. This gives the three-dimensional structure of the polysaccharide, the locations of ordered water molecules, and of potassium ions. The precise interactions among the three components at molecular level reveal that the water molecules are essential for the stability of the polysaccharide chains, for the binding of cations with the polymer molecules, and for the aggregation of the polymers, all of which are crucial for the gelation process. Computer modeling shows how the calcium ions can directly crosslink adjacent gellan molecules, but the potassium ions cannot, and this explains the stronger gelation properties of calcium gellan, even at very low ionic concentrations. L-glycerate, but not acetyl, groups interfere with the intermolecular association of native gellan molecules and are thus responsible for its weak and rubbery gels. PMID- 1746364 TI - Ordered water in hydrated solid-state polysaccharide systems. AB - Water molecules within a monolayer or so of macromolecular surfaces are often located in well-defined positions and have restricted mobility. These ordered water molecules play a role in stabilizing polysaccharide ordered structures and intermolecular interactions that are the basis of the rheological properties utilized in food systems. X-ray fiber diffraction can be used to determine the three-dimensional structures of polysaccharides in solid, but well-hydrated, polycrystalline fibers. In favorable cases, difference Fourier synthesis can be used to locate ordered water molecules in these systems, allowing one to visualize their functionally important interactions. These studies provide relevant evidence regarding water interactions in more hydrated systems and in solution. The functionality of ordered water in some polysaccharides used in food systems, as well as in some connective tissue glycosaminoglycans where the ordered water has been defined in considerable detail, as determined by fiber diffraction, is described in this chapter. These structures allow one to derive some general features of the role of ordered water in such systems. PMID- 1746365 TI - [Visual evoked potential and relative afferent pupillary defect in patients with unilateral optic neuritis]. AB - The relationships between relative afferent pupillary defect (RAPD) and visual evoked potential (VEP), visual acuity or visual field in 14 patients with idiopathic unilateral optic neuritis, were investigated during the period of recovery from an acute episode. Grading of RAPD into four steps mainly based upon an escape phenomenon in a swinging flashlight test, was used to determine the degree of RAPD. The degree of RAPD significantly correlated with a reduction in VEP amplitude, visual acuity and loss of central visual field, while it did not correlate with delay in VEP latency. These results suggest that RAPD is mainly related to the integrity of central vision, and that grading of RAPD, as well as a comparison of VEP amplitude between the affected and contralateral eyes, is useful for an objective evaluation of visual functions of the affected eyes in patients with unilateral optic neuritis. PMID- 1746366 TI - [Long-term changes in the corneal endothelium after intraocular lens implantation]. AB - The characteristics of the corneal endothelium of 134 eyes which underwent extracapsular cataract extraction and intraocular lens implantation from 1984 to 1990 were studied. We classified the initial 29 eyes as group 1 and the most recent 105 eyes as group 2. Endothelial cell loss of group 1 was much larger than that of the latter group, reflecting the degree of surgical damage. Endothelial cell of both groups decreased with index functions. The coefficient of variation of both groups showed no significant change during the observation period. The hexagonal cells of both groups decreased once after surgery, and it increased after one year in group 1, and after three months in group 2. However the late phase of the change of hexagonal cells appeared to have no relation to the degree of surgical damage. The change of hexagonal cells was supplemented by the appearance of pentagonal cells and heptagonal cells. PMID- 1746367 TI - [Retinochoroidopathy and systemic state in toxemia of pregnancy]. AB - We carried out a retrospective study of 74 patients with toxemia of pregnancy with reference to retinochoroidal complications. Thirty-two patients (43.2%) had overt retinochoroidal disease; 23 cases (group A) showed retinal hemorrhages and cotton-wool spots compatible with hypertensive retinopathy, while 9 cases (Group B) had widespread serous retinal detachment associated with choroidal vasculopathy. There was no significant difference between the two groups in the severity of toxemia of pregnancy, in the hematologic examinations or in the fetal prognosis, although Group A showed a higher rate of fetal mortality, and Group B had a more significantly decreased platelet count and lower concentration of fibrinogen that may indicate a mild form of chronic disseminated intravascular coagulopathy. PMID- 1746368 TI - [Optic neuritis]. PMID- 1746369 TI - [Effects of cigarette smoking on ocular circulation chronic effect on choroidal circulation]. AB - The effects of long-term smoking on choroidal circulation were studied. For this purpose, Wistar rats were made to inhale mainstream smoke for 30 minutes daily. After periods of inhalation (16 weeks and 25 weeks), choroidal blood flow (CBF) was measured by the hydrogen clearance method and the index of choroidal vascular resistance (systolic tail arterial pressure/CBF) was calculated. There was no significant difference in CBF between either smoking group (16 weeks and 25 weeks) and controls. However the index of choroidal vascular resistance increased significantly after inhalation of smoke for 25 weeks. No histopathological abnormalities were detected in the choroid and outer layer of the retina. The results suggested that long-term smoking might induce disturbance of choroidal circulation. PMID- 1746370 TI - [The distribution of actin on cultured oligodendrocytes from rat optic nerve]. AB - Two types of cultured oligodendrocytes (OLs) from rat optic nerve were analyzed for the distribution of actin, a major contractile protein, using immunocytochemistry. Type 1 OLs showed extensive network of processes and type 2 OLs showed elaborate membranous expansion along an extensive network. Actin was diffusely stained on an extensive network of processes in type 1 OLs and on the distal portion of membranous expansion in type 2 OLs, but some oligodendrocytes were not stained. It was demonstrated that the distribution of actin in type 1 OLs and type 2 OLs varied with development in oligodendrocyte differentiation and maturation. Our results suggest that undifferentiated and immature oligodendrocytes display remarkable cell movement to search for target axons, and differentiated and mature oligodendrocytes do not require cell movement when myelination has finished. In conclusion, it is considered that actin plays an important role in myelinogenesis. PMID- 1746371 TI - [Studies on the ultrastructure of the inner limiting membrane of the retina- distribution of anionic sites in the inner limiting membrane of the retina]. AB - For demonstrating ultrastructurally the distribution of anionic sites (AS) in the inner limiting membrane (ILM) of the rabbit's retina, the immersion method with cationic tracer, polyethyleneimine (PEI) was applied. This method was found to be simple and useful for the observation of AS in the ILM. In the posterior pole of the eyeball (visual streak and medullary ray), PEI particles were arranged evenly in the lamina rara (LR) of the ILM. The mean diameter of PEI particles was 20 nm, and intervals between them (40-50 nm) were the same as those of fine strands in the LR. However, the peripheral retina, the distribution of PEI particles were sparse and random, while in the lamina densa (LD) of each ILM, PEI particles were absent. AS stained with PEI were present in the residual vitreous fibers. These results may provide the morphological basis for the theory that AS of the ILM act as a charge barrier between the retina and the vitreous cavity. PMID- 1746372 TI - [A morphological classification of retinal ganglion cells in Chinese hamsters]. AB - Retinal ganglion cells in Chinese hamsters were morphologically classified into alpha, beta and gamma cells by the horseradish peroxidase labeling method. The alpha cells had large somatic and dendritic fields. The beta cells were small to medium in somatic size and had small dendritic field size. The gamma cells had small to medium somatic and large dendritic fields. Each cell type had either symmetrical or asymmetrical dendrites arising from the soma. The dendrites of alpha, beta and gamma cells extended into either the internal or external stratum of the inner plexiform layer. PMID- 1746373 TI - [Intraocular light transmission characteristics using a microfiber system]. AB - There have been some reports about light transmission into the vitreous, but few that have been measured directly in vivo. The author attempted to measure visible light and ultraviolet light using a microfiber system in the vitreous. Microfibers 0.6 mm in diameter were made. The microfiber system can be inserted into the vitreous at the pars plana and can measure the characteristics and intensity of the transmitted light. We used rabbit, monkey and aphakic rabbit eyes in this study. The light transmission into the vitreous of normal rabbits and monkey eyes gradually decreased from 400 nm to 360 nm, but the light transmission of the aphakic rabbit eyes did not distinctly decreased. This tendency was found in vivo and in vitro. It was considered that this system is useful to determine the light transmission characteristics of various eye conditions. PMID- 1746374 TI - [Analysis of electrically evoked response (EER) in relation to the central visual pathway of the cat (2). Response characteristics of the lateral geniculate neurons]. AB - To analyze the electrically evoked response (EER) in relation to the central visual pathway, the response characteristics of the lateral geniculate neurons (LGNs) of the EER in 35 anesthetized adult cats were studied. Responses of the LGNs showed interindividual variation of more than one log unit in terms of the stimulus threshold for electrical stimuli. As the stimulus intensity increased, the spikes with constant latencies were recorded, which showed bursts with much stronger stimuli. The latencies of the spikes were closely correlated with those of negative components of EER. The LGNs were divided into two major groups by the latency. The periodical and alternative excitation of these neurons contributed to form the first negative wave of EER. The latency of these two major groups of LGNs was reversed when the electrode polarity was changed. At higher stimulus intensities, the components with short latency became dominant and those with longer latency were suppressed. The above results suggested that the periodical excitation of LGNs and the formation of the prominent EER components may result from the interaction between on- and off-type retinal ganglion cells and amacrine cells. It was also suggested that the origins of the wavelets in negative waves of EER at strong stimuli are the bursts of the spikes of the visual cortex neurons. PMID- 1746375 TI - [Recovery of visual field defects in ischemic optic neuropathy and idiopathic optic neuritis]. AB - Fifty-four eyes of 41 patients with optic nerve disease demonstrating acute visual field defects without any traumatic, compressive, or other known etiology were classified into four categories. Those showing poor recovery of visual field defects were ischemic optic neuropathy which was subclassified into either anterior ischemic optic neuropathy (AION) or posterior ischemic optic neuropathy (PION) according to the ophthalmoscopic changes in the optic nerve head. Those showing good recovery of visual field defects were idiopathic optic neuritis which was subclassified into either papillitis or retrobulbar neuritis according to the ophthalmoscopic pathology of the optic disc. Patients with ischemic optic neuropathy were significantly older than those with optic neuritis. All eyes with optic neuritis showed good recovery of vision, whereas those with ischemic optic neuropathy showed varying outcomes of vision. With regard to the pattern of field defect, central or paracentral scotoma was predominant in all but eyes with AION in which altitude defect predominated. Pale swelling of the optic nerve head and angiographic evidence of circulatory disturbance in the optic disc or adjacent choroid were common findings in eyes with AION, whereas such findings were never observed in eyes with papillitis. The amplitude of pattern visual evoked potential was significantly lower in eyes with PION than in those with retrobulbar optic neuritis. Four patients classified as optic neuritis developed into multiple sclerosis in the follow-up study. It was concluded that poor recovery of visual field defect is one of the most convincing evidences for the diagnosis of ischemic optic neuropathy. PMID- 1746376 TI - [Visual functions of optic neuritis in children caused by demyelinating disease]. AB - Optic neuritis in childhood caused by demyelinating disease is very rare, and its effect on visual function has not been well documented. The visual function of 11 patients treated in the last 11 years was retrospectively studied and the results were compared with 15 cases of optic neuritis of unknown etiology. Optic neuritis in children with demyelinating disease was characterized as follows. 1. abnormal visual evoked cortical potentials (VECP) and color vision were found not only in the affected eye but also in the non-affected fellow eye, 2. VECPs became normal long after the recovery of visual acuity, 3. full recovery of visual function took longer, 4. at onset, vision was more severely affected, but showed a good outcome. These findings provide useful information to make a diagnosis of multiple sclerosis even at the first attack of optic neuritis. PMID- 1746377 TI - Beyond critical care: appearance-related afflictions. AB - There is no reason to believe that humans will not continue in their never-ending quest for self-fulfillment, for in it mankind carries forward the purpose of life itself. Through the art and science of aesthetics, specialists throughout the various health professions are cooperating to help individuals from all socio economic backgrounds overcome appearance-related afflictions and improve the quality of life. (Figure 10). PMID- 1746378 TI - AHCPR estimates cost of treating HIV infection. PMID- 1746379 TI - The odd couple. PMID- 1746380 TI - Bicycling and ulnar tunnel syndrome. PMID- 1746382 TI - Domestic violence hotline. PMID- 1746381 TI - Pregnant patients with HSV infection. PMID- 1746383 TI - Shoulder manipulation by DOs. PMID- 1746384 TI - AAFP white paper on proprietary relationships: just do the right thing. PMID- 1746385 TI - The National Screening Initiative and the family physician. PMID- 1746386 TI - Common oral mucosal lesions in adults. AB - Patients often present to family physicians with oral lesions. According to a recent study, the 10 most common oral mucosal lesions comprise almost three quarters of oral lesions. The most common oral lesions are leukoplakia, tori, inflammatory lesions, fibromas, Fordyce's granules, hemangiomas, ulcers, papillomas, epuli and varicosities. PMID- 1746387 TI - Acute sinusitis: diagnosis and treatment update. AB - Acute sinusitis in adults is manifested by fever, facial pain and purulent rhinorrhea, but children--who rarely have headache or facial tenderness--have persistent cough in addition to fever and purulent rhinorrhea. Sinus transillumination is diagnostically useful only in adults. In children, maxillary sinus radiographs are indicated. New studies show ultrasound examination to be less sensitive than plain radiographs. Cultures obtained by aspiration of the maxillary sinuses are useful in complicated cases. Amoxicillin is still effective as first-line treatment, but treatment failure requires a prompt change to trimethoprim-sulfamethoxazole or ciprofloxacin. Nosocomial sinusitis requires coverage for gram-negative bacteria, including Pseudomonas aeruginosa. Immunocompromised patients, including those with acquired immunodeficiency syndrome, require treatment for fungal organisms. Decongestants are of unproven value. Referral for irrigation and surgical drainage is indicated for recurrent or recalcitrant sinusitis. Flexible endoscopy allows visualization and debridement of diseased tissue in cases of chronic sinusitis. PMID- 1746388 TI - Psychosocial issues in symptomatic HIV infection. AB - Psychosocial issues are a major factor in the quality of life of a patient with advanced human immunodeficiency virus infection. To provide effective, supportive care, the physician must assess the patient's psychosocial needs, with an understanding of the patient's sociocultural background. Good communication and a multidisciplinary team approach are essential aspects of successful management. Unconditional emotional support and both verbal and nonverbal expressions of caring increase patient compliance and comfort. Appropriate treatment of neuropsychiatric syndromes and debilitating physical symptoms also add significantly to the patient's quality of life. Most importantly, the patient must be given the opportunity to be an active participant in decisions about treatment and lifestyle. PMID- 1746389 TI - Risk factors for poor nutritional status in older Americans. AB - Inappropriate dietary intake and chronic disease or disability place a substantial number of older adults at high risk of malnutrition. Malnutrition often results in considerable dysfunction and disability, reduced quality of life and, in some instances, premature or increased morbidity and mortality. Nutrition screening should prevent nutrition-related problems or allow early intervention. The elements that contribute to nutritional problems in the elderly must be clearly identified and prioritized. The desired goal of nutrition screening is a more vigorous older population able to maintain optimal nutrition, resulting in improved health and quality of life. PMID- 1746390 TI - Anticoagulants, iliopsoas hematoma and femoral nerve compression. AB - A case of bilateral compression femoral neuropathy due to iliopsoas muscle hematomas during anticoagulant therapy is described. Diagnosis was confirmed with computed tomographic scan. The right hematoma was larger than the left and caused a more severe femoral neuropathy. The hematoma on the right side was surgically evacuated, and the left-sided one was treated conservatively. The patient had a complete recovery. PMID- 1746391 TI - Weight-training injuries in children and adolescents. AB - Thousands of children and adolescents participate in weight lifting for recreation or as a means of training for sports. Weight lifting can cause serious musculoskeletal injuries, such as ruptured intervertebral discs, spondylolysis and spondylolisthesis, fractures and meniscal injuries of the knee. Deaths related to weight lifting have been reported. Although the incidence of weight lifting injuries is not well documented in children and adolescents, several reports indicate that few injuries occur in carefully supervised programs. The most common cause of injury appears to be loss of form when heavy weights are lifted. Proper technique, good supervision and training programs appropriate to the athlete's level of physical and emotional maturity are important. PMID- 1746392 TI - An introduction to tympanometry. AB - The tympanogram is an objective measure of middle ear effusion or eustachian tube dysfunction. It provides information about the compliance or mobility of the tympanic membrane, the pressure within the middle ear and the volume of the external ear canal. Tympanograms are classified as type A (normal), type B (indicating fluid behind the tympanic membrane) or type C (indicating eustachian tube dysfunction). The objective data obtained by tympanometry are a useful adjunct in the diagnosis and follow-up of middle ear disease. PMID- 1746393 TI - Commonly used suture materials in skin surgery. AB - The ideal suture is strong, handles easily and forms secure knots. It causes minimal tissue inflammation and does not promote infection. It stretches, accommodates wound edema and recoils to its original length with wound contraction. Ideally, it is also inexpensive. Although no single suture material possesses all of these features, proper selection of sutures helps achieve better results in skin surgery. Among the absorbable sutures are catgut and treated catgut (both are used infrequently) and the synthetic sutures, which are designed for good tensile strength, easy handling and low tissue reactivity. Nonabsorbable sutures include silk (now infrequently used) and several synthetic materials designed for elasticity, easy handling, good knot security and minimal tissue irritation. PMID- 1746394 TI - CPR in hospitalized patients: when is it futile? AB - When cardiac or pulmonary arrest occurs in hospitalized patients, cardiopulmonary resuscitation (CPR) is often futile. Although "do-not-resuscitate" orders are widely used and presumably screen out many patients who are poor candidates for CPR, recent studies have shown that an average of only 13 percent of patients receiving CPR in the hospital survive to discharge. An average of 4 percent of patients receiving CPR in general ward settings survive. Of those who do survive after CPR, many are in a persistent vegetative state or a chronic dependent condition. Patients with malignancy, sepsis, pneumonia, renal failure, diabetes or advanced age have a low chance of surviving after CPR. It is important for both patients and physicians to make a realistic appraisal of the likely outcome of CPR. PMID- 1746395 TI - Treatment of bacterial prostatitis. AB - Bacterial prostatitis can be distinguished from nonbacterial prostatitis on the basis of the symptoms, the findings on physical examination and the results of microbiologic testing. Evaluation of fractionated urine specimens, including expressed prostatic secretions, is helpful in making the diagnosis. Bacterial prostatitis may be acute or chronic. Acute prostatitis can be a serious illness requiring inpatient treatment with parenteral antibiotics. Chronic prostatitis is difficult to cure, and prolonged antibiotic therapy is required for eradication of symptoms. The most useful agents for the treatment of prostatitis include trimethoprim-sulfamethoxazole and the fluoroquinolones. Evidence indicates that fluoroquinolones may result in superior symptom control and microbiologic cure. PMID- 1746396 TI - Patient-controlled analgesia. AB - It has become increasingly obvious that traditional narcotic dosage schemes are not optimally effective in relieving pain. Inadequate relief of pain results in increased patient morbidity, probably due to adverse effects on the neurologic, endocrine, pulmonary and cardiovascular systems. Insufficient pain relief also contributes to patient dissatisfaction. Patient-controlled analgesia allows a patient to balance analgesic levels with the degree of pain relief required. This analgesic technique is easy to use and is well accepted by patients, physicians and nurses. Significant benefits include earlier ambulation, decreased overall narcotic use, improved postoperative pulmonary function, shorter hospital stay and reduced health care costs. PMID- 1746397 TI - Update on breast implants. PMID- 1746398 TI - AAFP Congress approves statement on ethics of proprietary relationships. PMID- 1746399 TI - AAFP age charts for periodic health examinations: 19 months to six years. PMID- 1746400 TI - Combination test for HIV-1 and HIV-2 licensed. PMID- 1746401 TI - Didanosine approved for advanced AIDS. PMID- 1746402 TI - Graphical description of health threat defeats parent company opinion. PMID- 1746403 TI - Confusion regarding asbestos data and censoring. PMID- 1746404 TI - Hexamethylenetetramine: a review. PMID- 1746405 TI - Guideline for chemical exposure to the skin. PMID- 1746406 TI - A transportable, remote sensing, infrared air-monitoring system. AB - A transportable, remote sensing instrument has been built that is capable of performing real-time quantitative analysis of gas and vapor contaminants of workplace air. The emphasis in this system is on simplicity and sensitivity for use over pathlengths of up to 40 m. A method was developed to overcome the effect of nonanalyte species present in the background spectrum on the quantitation of analytes in the sample spectrum. In addition, results demonstrated that instrument response was proportional to the beam pathlength under homogeneous concentration conditions. The application of software capable of qualitative analysis was also demonstrated. PMID- 1746407 TI - Modeling a worker's exposure from a hand-held source in a uniform freestream. AB - The phenomenon of boundary layer separation can be an important factor in determining a worker's exposure to toxic airborne pollutants. A conceptual model was developed to understand this phenomenon and to predict the average concentration in the reverse flow region downstream of a worker in a uniform freestream. Subsequently, the assumptions of this model were tested experimentally in wind tunnel studies. On the basis of these results, a revised model is presented and validated by using a tracer gas method. The revised model provides a reasonable estimate of the average concentration in the reverse flow region of the mannequin. Empirical models are presented that relate both the average concentration in the reverse flow region and the breathing zone concentration to the body dimensions and the freestream air velocity. Applications and limitations of the results are discussed. PMID- 1746408 TI - Evaluation of the acute toxicity of silahydrocarbon. AB - Silahydrocarbon (SHC) is a base stock for a candidate high-temperature hydraulic fluid. Because United States Air Force personnel working with SHC may be exposed to potential health hazards, a complete battery of acute toxicity tests was performed with the fluid. A single neat dose of 0.1 mL SHC into New Zealand White (NZW) rabbit eyes resulted in slight conjunctival irritation 1 hr after treatment in all unflushed eyes and one of three flushed eyes. Conjunctival irritation persisted through 24 hr but dissipated by 48 hr. Rinsing the eyes after treatment was of questionable benefit. A single treatment of 0.5 mL neat SHC to rabbit skin produced negative results for all but a single animal, which had very slight erythema at the test site 48 hr after treatment. Guinea pigs failed to exhibit a sensitization response following repeated application of SHC. A single oral dose of 5 g SHC/kg body weight given to five male and five female F-344 rats and a single dermal dose of 2 g SHC/kg body weight applied to five male and five female NZW rabbits resulted in no deaths or signs of toxic stress. Five male and five female F-344 rats were exposed to 4.8 mg/L (near limit concentration) of aerosolized SHC for 4 hr. All male rats and four female rats survived. During exposure, the animals exhibited signs of eye and upper respiratory irritation. PMID- 1746409 TI - Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene. AB - Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746410 TI - Exposure to airborne asbestos associated with simulated cable installation above a suspended ceiling. AB - Installing cable above a suspended ceiling in the presence of asbestos-containing fireproofing is an example of an activity that may disturb in-place asbestos and associated dust and debris. Two simulations of cable installation were conducted in a room of an unoccupied school to test the extent of such disturbance and resulting elevations in airborne asbestos. Average airborne asbestos concentrations in the room increased over 500-fold during the simulations, with several samples exceeding 50 structures per cubic centimeter (s/cm3), as measured by transmission electron microscopy (TEM) with an indirect preparation technique. Elevated concentrations persisted during a subsequent cleaning of horizontal surfaces in the room and for several hours thereafter. Personal samples collected on the cable installers yielded TEM measurements averaging approximately 68 s/cm3 for the two simulations. PMID- 1746411 TI - Wood dust exposure during furniture manufacture--results from an Australian survey and considerations for threshold limit value development. AB - A survey of time-weighted average (TWA) personal inhalable dust exposures for woodworkers in 15 Australian furniture factories was undertaken. There was significant variation in the individual dust measurements with mean exposures of 3.2, 5.2, and 3.5 mg/m3 for wood machinists, cabinetmakers, and chair framemakers, respectively. Hardwoods, softwoods, and reconstituted woods are used in the industry, but only minor differences in mean exposures or particle size distributions were found for the broad categories. In addition, a modified British Medical Research Council respiratory questionnaire was used to obtain information about work-related symptoms and job activities. Compared with a control group, the woodworkers reported more eye, ear, and nasal problems, with the differences being statistically significant. However, among the woodworkers themselves, with the exception of several nasal symptoms, the prevalences of reported symptoms were poorly correlated with gravimetric measurements of personal dust exposure. The problem of selection bias in cross-sectional studies is discussed. For a mean TWA personal exposure of about 3 mg/m3, hardwood users were more likely to report nasal symptoms than users of reconstituted wood. The question of appropriate exposure standards for woods in general is addressed by reference to those important health effects, besides sino-nasal cancer, that have been investigated. Further exposure guidelines should be formulated for groups of woods that are known to cause a common health effect, such as nasal/respiratory sensitization. PMID- 1746412 TI - A measure of goodness-of-fit for the lognormal model applied to occupational exposures. AB - The lognormal distribution is often applied to occupational exposures, yet the assumption of lognormality is rarely verified. This lack of rigor in evaluating the appropriateness of the lognormal model has resulted, in part, from the difficulty of applying formal goodness-of-fit tests. When evaluation of model fit has been attempted, occupational hygienists have relied upon probability plotting of exposures rather than upon formal statistical methods. The goal of this work was to develop for the occupational hygienist a simple quantitative evaluation to supplement the probability plot. A measure of goodness-of-fit to the lognormal model based on the ratio of two estimators of the mean of the distribution, the simple or direct estimate of the mean and the maximum likelihood estimate of the mean of a lognormal distribution, is described. This new measure, the ratio metric, is a simple extension of calculations made routinely by many occupational hygienists. Results from using the ratio metric were compared to probability plotting and to two traditional measures of goodness-of-fit, the Lilliefors test and the W test, for two occupational exposure data sets. The results of the ratio and W tests are comparable for a variety of occupational exposure data, but the Lilliefors test is overly conservative and does not detect several cases of gross deviations from lognormality. The ratio metric is an effective alternative to the Lilliefors test and is easier to perform than the W test for the range of data usually encountered by occupational hygienists. Occupational hygienists are encouraged to use the ratio metric in conjunction with the probability plot in evaluating the lognormal assumption. PMID- 1746413 TI - Ventricular remodeling and unloading following myocardial infarction. A symposium. April 5-6, 1991, Barbados. PMID- 1746414 TI - Early treatment of acute myocardial infarction with angiotensin-converting enzyme inhibition: safety considerations. SMILE pilot study working party. AB - The use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (AMI) is based on their capacity to limit ventricular enlargement and dysfunction. To date, the safety profile of administration of ACE inhibitors early in the course of AMI has not been established. In-hospital and long-term consequences of treatment with the ACE inhibitor zofenopril initiated within 24 hours of the onset of symptoms were compared with those of standard treatment in an open-label trial involving 204 patients with AMI who were not undergoing thrombolytic treatment. Zofenopril promptly blocked ACE activation. Blockade was almost complete (91 +/- 6%) after 72 hours and paralleled decreases in systolic blood pressure. Systemic blood pressure was acutely reduced by zofenopril, and severe but reversible hypotension occurred in 15% of hospitalized patients and in 3% of those treated over the long term. No adverse clinical or biochemical events were reported during the course of zofenopril therapy. Overall cardiovascular mortality was not significantly reduced by early zofenopril compared with placebo therapy (7.8% vs 10.7% [difference not significant]). The inhospital incidence of acute left ventricular failure and ventricular arrhythmias decreased by 63% and 39%, respectively, among zofenopril-treated patients, who also reported fewer anginal episodes both acutely (68% reduction) and over the long term (56% reduction) and did not require as much drug treatment (i.e., diuretics, digoxin, and/or anti-ischemic agents) during the follow-up phase. Left ventricular size decreased and ejection fraction (EF) increased in patients who received zofenopril, and the improvement was greater among patients with poorer ventricular function (EF less than 40%). Early administration of ACE inhibitors may therefore constitute a safe form of therapy for patients with AMI, particularly when the event is complicated by clinical signs or evidence of ventricular dysfunction. PMID- 1746415 TI - Early intervention with angiotensin-converting enzyme inhibitors during thrombolytic therapy in acute myocardial infarction: rationale and design of captopril and thrombolysis study. CATS investigators group. AB - The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase prostacyclin and bradykinin levels. In the chronic phase, ventricular remodeling may be attenuated. At present, a large number of controlled clinical trials mainly focusing on the effects of ACE inhibition in the chronic phase are underway. Only a few studies concentrate on the effect of acute intervention with ACE inhibitors in ischemia-reperfusion, i.e., thrombolysis in myocardial infarction. In April 1990 under auspices of the Interuniversity Cardiology Institute of the Netherlands, a large nationwide acute intervention trial with captopril in 280 patients receiving thrombolytic therapy was started, the Captopril and Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of ACE inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately on thrombolysis and during the first year after myocardial infarction. PMID- 1746416 TI - Influence of severity of heart failure on the efficacy of angiotensin-converting enzyme inhibition. AB - Angiotensin-converting enzyme (ACE) inhibition slowed the progression of congestive heart failure (CHF) in 170 patients who were randomly assigned to either captopril or placebo in the Munich Mild Heart Failure Trial. The two major end points were progression from New York Heart Association (NYHA) functional classes I, II, or III to class IV, despite optimal, adjusted standard therapy, and death due to CHF. The relative risk for progressive CHF with captopril therapy was 0.34 (95% confidence interval = 0.17-0.68; p = 0.01). A total of 52 prerandomization variables were tested to determine their contribution to disease progression. Logistic regression analysis revealed 5 independent risk factors for progressive CHF: NYHA class, left ventricular end-systolic diameter, need for diuretic, age, and cardiothoracic ratio. The presence of greater than 2 of these risk factors increased the odds ratio for progression to 8.13 (p less than 0.001) compared with the presence of 0-2 risk factors. However, the effectiveness of captopril in preventing progression was higher within the subgroup of patients who had less severe CHF: the odds ratio was 0.12 (95% confidence interval = 0.03 0.45; p less than 0.01) for patients in NYHA class I or II on captopril and was 0.83 for those in class III. We conclude that the severity of CHF, as represented by the above-defined risk factors, is directly related to the likelihood for the development of progressive heart failure. However, the less severe the heart failure, the more effective the treatment with captopril will be in preventing disease progression. Thus, ACE inhibition has considerable potential for improving the prognosis of patients with mild heart failure. PMID- 1746417 TI - Effects of captopril on contractility after myocardial infarction: experimental observations. AB - After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746418 TI - Fourth International Study of Infarct Survival: protocol for a large simple study of the effects of oral mononitrate, of oral captopril, and of intravenous magnesium. ISIS-4 collaborative group. AB - The fundamental aim of the International Studies of Infarct Survival (ISIS) collaborative group is to assess reliably the balance of any benefits and risks for widely practicable treatments that might produce moderate but worthwhile mortality reductions in patients with suspected acute myocardial infarction. Substantial numbers of lives might be saved by such treatments, but benefits of the size that can realistically be expected may be reliably detected only by randomized trials involving some tens of thousands of patients. In order to recruit such numbers, ISIS involves almost no extra work for collaborators: hence, busy general hospitals--where the majority of acute myocardial infarction patients are actually treated--can take part easily. The ability of the ISIS trials to yield clear, reliable answers depends entirely on the collaboration of many doctors and nurses in the participating hospitals. For this reason, publication of the final results is in the names of all the collaborators. All patients, high risk as well as low risk, presenting within 24 hours of the onset of suspected acute myocardial infarction are eligible for ISIS-4, provided that the responsible physician does not initially consider there to be any clear indications for, or clear contraindications to, any one of the trial treatments- nitrate, angiotensin-converting enzyme inhibitor, or magnesium. Patients are randomized between 1 month of oral controlled-release mononitrate or placebo; between 1 month of oral captopril or placebo; and between 24 hours of intravenous magnesium or open control (i.e., no infusion). (Patients who are to be given intravenous or other non-trial nitrate for just a few days can still be entered). In this trial, 3 quite different treatments will each be evaluated. At first glance, this may appear to complicate the results, but in fact appropriate statistical analysis of this "factorial" design will allow all patients to contribute fully to assessment of the separate effects of each treatment (while also providing important information about the combined effects). Apart from giving the trial treatments, all other aspects of individual patient management are left entirely to the responsible physician to decide. For example, previous trials in suspected acute myocardial infarction have shown that, for many categories of patients, antiplatelet and fibrinolytic therapy can save lives. Hence, most collaborating doctors will wish to give antiplatelet therapy routinely and to start fibrinolytic therapy in many of their patients before randomizing them in ISIS-4.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1746419 TI - Relation between acute ventricular arrhythmias, ventricular late potentials and mortality in acute myocardial infarction. AB - The relation between ventricular late potentials and the occurrence of acute (in hospital) and hyperacute (before hospital admission) ventricular tachycardia or fibrillation was studied in 281 consecutive patients with uninterrupted acute myocardial infarction. The prevalence of late potentials was significantly higher in patients with than without ventricular tachycardia/fibrillation (65 vs 22%; p less than 0.01). These relations persisted among patients with left bundle branch block, although a different definition was used for identifying late potentials in these patients. Multivariate analysis showed that presence of late potentials and peak creatine kinase enzyme level were the only 2 independent variables associated with early ventricular tachycardia/fibrillation. Total in-hospital mortality, as well as in-hospital cardiac mortality, was significantly higher among patients with than without acute ventricular tachycardia/fibrillation. However, at 1 year, mortality rates did not differ between the 2 groups. The following conclusions were drawn from this study: (1) Late potentials are closely related to ventricular tachycardia/fibrillation in hyperacute and acute phases of infarction. (2) Presence of left bundle branch block does not mitigate against the finding of late potentials in these patients. (3) Early ventricular tachycardia/fibrillation in acute infarction is related to large infarctions and to a high in-hospital mortality rate. PMID- 1746420 TI - Importance of myocardial infarct artery patency on the prevalence of ventricular arrhythmia and late potentials after thrombolysis in acute myocardial infarction. AB - Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction. PMID- 1746421 TI - Usefulness of QRST time-integral values of 12-lead electrocardiograms in diagnosing healed myocardial infarction complicated by left bundle branch block. AB - The usefulness of QRST time-integral (IQRST) values of 12-lead electrocardiograms for diagnosing a prior myocardial infarction complicated by left bundle branch block (LBBB) was determined. The study consisted of 25 patients with LBBB (11 with and 14 without myocardial infarction). The IQRST values in each lead point of 12-lead electrocardiograms were calculated. Data from 607 normal subjects were used as controls and mean +/- 2 standard deviations was regarded as the normal range. The following parameters were derived: number of leads less than the normal range of IQRST values (nQRST) and sum of the differences between the normal mean IQRST value and IQRST value of a given patient in leads where this value was less than the normal range (sigma QRST). The criteria of nQRST (12 lead) greater than or equal to 5 and sigma QRST (12-lead) greater than or equal to 500 microV in 12-lead electrocardiograms were selected on a relative cumulative frequency distribution and demonstrated the presence of a myocardial infarction in LBBB with a sensitivity of 82% and a specificity of 100% for each. With regard to the localization of the myocardial infarction, the criterion of sigma QRST (V1-6) greater than or equal to 300 microV in leads V1-6 of 12-lead electrocardiograms demonstrated the presence of an anterior myocardial infarction in the LBBB with a sensitivity of 88% and a specificity of 77%. It was difficult to localize an inferior myocardial infarction in patients with LBBB by using IQRST values of inferior leads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746422 TI - Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity. AB - Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 +/- 7 (4.84 +/- 0.18 mmol/liter), 134 +/- 6 (3.47 +/- 0.15 mmol/liter), 41 +/- 3 (1.06 +/- 0.08 mmol/liter) and 106 +/- 30 mg/dl (1.20 +/- 0.03 mmol/liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 +/- 4%, p less than 0.05 vs baseline) and diseased (19 +/- 4%, p less than 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p less than 0.001) and diseased (r = 0.62, p less than 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746423 TI - Effects of serum lipid levels on restenosis after coronary angioplasty. AB - Although the association of serum lipid levels with the risk of atherosclerosis is well-recognized, the relation between these levels and restenosis after coronary angioplasty is uncertain. This study examines 186 patients enrolled in a trial of fish oil for prevention of restenosis. Fasting lipid levels (cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides) were measured before angioplasty, and in 90 patients repeated at 6-month follow-up. Fifty-nine patients (32%) developed clinical restenosis confirmed by angiography. Patients who went on to develop restenosis underwent multivessel angioplasty (p less than 0.05) and were more likely to be on lipid-lowering therapy at baseline (27 vs 13%; p less than 0.05). In addition, they had higher baseline cholesterol/HDL ratios (6.5 +/- 2.2 vs 5.9 +/- 2.0; p less than 0.05) and triglyceride levels (233 +/- 210 vs 183 +/- 112 mg/dl; p less than 0.05). Multiple logistic regression analysis confirmed cholesterol/HDL ratios at baseline (p = 0.021) and follow-up (p = 0.0008) to be independent predictors of risk for restenosis. Using these data, regression lines have been developed that predict risk of restenosis based on type of procedure and on lipid values. These results suggest that serum lipid levels may be associated with the risk of clinical restenosis after coronary angioplasty. PMID- 1746424 TI - Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE) AB - Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained. PMID- 1746425 TI - Causes and correlates of death after unsupported coronary angioplasty: implications for use of angioplasty and advanced support techniques in high-risk settings. AB - To better understand the factors predisposing a patient to death after elective percutaneous transluminal coronary angioplasty (PTCA) and to gain insight into indications for high-risk PTCA both with and without adjunctive use of support devices, the outcomes of 8,052 consecutive procedures were reviewed. Death occurred after 32 procedures (0.4%) and was directly related to coronary artery closure in 26 (81%) of these cases. Left ventricular failure due to vessel closure at the dilated site, the most common cause of death, was independently correlated with female sex (p less than 0.001), "jeopardy score" (p less than 0.001) and PTCA of a proximal right coronary artery site (p = 0.002), but not with left ventricular ejection fraction or presence of multivessel disease. Right ventricular failure after closure of the proximal right coronary artery, and left main coronary dissection accounted for the majority of the remaining deaths. Systolic blood pressure immediately after coronary artery closure was also closely correlated with jeopardy score, and cardiogenic shock was frequent in women with scores greater than or equal to 3.5 and in men with scores greater than or equal to 5.0. These data highlight the superiority of the jeopardy score versus ejection fraction in the determination of risk, stress the importance of gender in determining outcome and point to the need for better means of right ventricular protection from severe ischemia. Therefore, an initial framework for rational use of PTCA and support devices in the high-risk setting is established. PMID- 1746426 TI - Value of transesophageal echocardiography during complex or high-risk coronary interventions in the cardiac catheterization laboratory. AB - The increasing complexity of coronary intervention and the limitations of hemodynamic and electrocardiographic monitoring have facilitated the introduction of new imaging techniques in the cardiac catheterization laboratory. Transesophageal echocardiography (TEE) has proved valuable for left ventricular (LV) monitoring during high-risk surgery, but its reported use in the cardiac catheterization laboratory has been limited. Accordingly, we assessed the feasibility and value of TEE during complex or high-risk coronary intervention in the catheterization laboratory. The TEE probe was successfully introduced in 53 of 54 (98%) attempted cases. The primary imaging goals were LV monitoring in 39 (74%), left main coronary artery (LMCA) imaging in 9 (17%) and both in 5 (9%) cases. LV monitoring was successful in 43 of the 44 (98%) attempted cases. In 25 (58%) of these, additional important observations were made by TEE that were not apparent by symptoms, or hemodynamic, electrocardiographic or radiographic monitoring. These included unexpected changes in regional myocardial function (n = 20), alteration in LV size (n = 2), exclusion of considered pericardial tamponade (n = 2) and detection of unsuspected mitral regurgitation (n = 1). Management of the interventional procedure was directly influenced by the findings of TEE in 11 of the 43 (26%) monitored cases. The LMCA was successfully visualized in 13 of the 14 (93%) attempted cases. In 11 of these, measurement of the stenotic lesion diameter by TEE correlated well with quantitative angiography both before (r = 0.83, standard error of the estimate = 0.01, p less than 0.002) and after (r = 0.80, standard error of the estimate = 0.03, p less than 0.005) intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746427 TI - Effects of cardiac denervation on atrioventricular nodal accommodation and hysteresis. AB - Conduction through the atrioventricular (AV) node is significantly altered by changes in autonomic tone. AV nodal accommodation (time-dependent changes in AV nodal conduction after a sudden change in atrial cycle length) and AV nodal hysteresis (asymmetry of AV nodal accommodation after directionally opposite atrial pacing cycle length changes) have been characterized in humans. Studies in dogs after cardiac transplantation suggest that the rapid phase of AV nodal accommodation is altered following ablation of neural input to the AV node. To determine if cardiac denervation alters AV nodal accommodation and hysteresis in humans, 13 patients after orthotopic cardiac transplantation and 12 control patients with normal AV nodal function were studied. Atrial pacing was performed for 1 minute at different pacing cycle lengths and AH or AV intervals were measured after cycle length changes. The rapid phase of accommodation is defined as the time required for the AV interval to reach 75% of the final AV interval. During abrupt changes from long to short pacing cycle lengths, the rapid phase of accommodation took 3.2 +/- 1.0 and 4.3 +/- 1.0 beats in control subjects and transplant patients, respectively (p = not significant [NS]). When going from short to long pacing cycle lengths, the rapid phase of accommodation took 1.7 +/- 1.2 and 2.1 +/- 1.8 beats in control subjects and transplant patients, respectively (p = NS). Hysteresis of 1.5 +/- 1.3 and 2.1 +/- 1.4 beats was noted in the control and transplant groups, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746428 TI - Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]). AB - Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension. PMID- 1746429 TI - Systemic and left ventricular responses to exercise stress in asymptomatic patients with valvular aortic stenosis. AB - Patients with heart disease may have myocardial ischemia or left ventricular (LV) dysfunction without symptoms. The exercise responses of 14 asymptomatic patients with valvular aortic stenosis (AS) were studied using treadmill testing, thallium 201 scintigraphy and radionuclide angiography. Compared with age- and gender matched control subjects, patients with AS demonstrated reduced exercise tolerance (10.7 +/- 2.5 vs 13.3 +/- 4.2 min; p = 0.06) and maximal oxygen consumption (26.7 +/- 6.3 vs 36.3 +/- 9.5 ml O2/min/kg; p = 0.004) associated with decreased peak systolic blood pressure response to exercise (177 +/- 18 vs 214 +/- 42 mm Hg; p less than 0.004). Ten of 14 patients developed ST-segment depression during exercise, only 3 of whom had reversible thallium defects. Patients with AS tended to have greater LV ejection fractions at rest (65 +/- 11 vs 58 +/- 7; p = 0.08) and significantly decreased early peak filling rates (4.8 +/- 1.3 vs 6.1 +/- 0.6 stroke volume/s; p = 0.003) compared with those of control subjects. During maximal supine exercise, patients with AS had less of an increase in ejection fraction (2 +/- 9 vs 15 +/- 7%; p less than 0.001) associated with a decrease in end-diastolic (-7 +/- 15 vs +5 +/- 16%; p = 0.06) and stroke (-6 +/- 17 vs +30 +/- 13%; p less than 0.001) volumes from baseline measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746430 TI - Doppler echocardiographic findings in adults with severe symptomatic valvular aortic stenosis. Balloon Valvuloplasty Registry Echocardiographers. AB - Baseline echocardiographic data in 680 adults (mean age 78 years) undergoing balloon aortic valvuloplasty at 24 medical centers were analyzed to describe the degree of outflow obstruction in patients with symptomatic aortic stenosis. Maximal aortic jet velocity ranged from 2.3 to 6.6 m/s (mean 4.4 +/- 0.8) and continuity equation valve area ranged from 0.1 to 1.4 cm2 (mean 0.6 +/- 0.2). Of note, 36% had a jet velocity less than or equal to 4.0 m/s but only 3% had a valve area greater than 1.0 cm2 due to a high prevalence of impaired systolic function (54%). Outflow tract diameter was poorly correlated with body surface area (p = 0.26), although the group mean diameter was smaller in women than in men (1.9 +/- 0.2 vs 2.1 +/- 0.3 cm, p = 0.0001). Mean pressure gradient was related closely to maximal gradient (r = 0.92) and to maximal jet velocity (mean delta P = 2.4 V2 + 0.75 mm Hg). Simpler measures of aortic stenosis severity were correlated with Doppler and invasive valve area as follows: maximal jet velocity (r = -0.36 and -0.32), mean gradient (r = -0.33 and -0.29), outflow tract to jet velocity ratio (r = 0.67 and 0.40), and the fractional shortening velocity ratio (r = 0.29 and 0.22). This study demonstrates marked variability in stenosis severity in symptomatic adults referred for balloon aortic valvuloplasty. The absence of a predictable relation between outflow tract diameter and body size emphasizes the importance of this measurement in each patient if definition of valve area is needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746431 TI - Doppler echocardiographic estimation of mitral valve area during changing hemodynamic conditions. AB - Patients with mitral stenosis often present during periods of hemodynamic stress such as pregnancy or infections. The Doppler pressure half-time method of mitral valve area (MVA) determination is dependent on the net atrioventricular compliance as well as the peak transmitral gradient. The continuity equation method of MVA determination is based on conservation of mass and may be less sensitive to changes in the hemodynamic state. To test this hypothesis, 17 patients admitted for catheterization with symptomatic mitral stenosis and no more than mild regurgitation underwent Doppler echocardiography at rest and during supine bicycle exercise targeted to an increase in heart rate by 20 to 30 beats/minute. Net atrioventricular compliance was also estimated noninvasively. Cardiac output and transmitral gradient increased significantly during exercise (p less than 0.001), while net atrioventricular compliance decreased (p less than 0.001). MVA by the pressure half-time method increased significantly during exercise from 1.0 +/- 0.2 to 1.4 +/- 0.4 cm2 (p less than 0.001). There was no significant difference in MVA estimation using the continuity equation comparing rest to exercise, with the mean area remaining constant at 0.8 +/- 0.3 cm2 (p = 0.83). Thus, during conditions of changing hemodynamics, the continuity equation method for estimating MVA may be preferable to the pressure half-time method. PMID- 1746432 TI - Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960. AB - This study was designed to determine the clinical status, cause of death, and effects of pulmonary vascular disease and conduction abnormalities 30 to 35 years after surgery in 296 consecutive surviving patients of closure of ventricular septal defect. Of the 296 patients, current status was determined by contact with patient and physician in 290 cases, with 6 (2%) lost to follow-up (7,912 patient years are included). Cardiac catheterization after surgery in 168 patients showed complete closure of the defect in 80%. Death occurred in 59 patients (20%), with higher mortality rates in those operated on after the age of 5 years, those with pulmonary vascular resistance greater than 7 units (51%), and those with complete heart block (78%). Of 37 patients with transient heart block after surgery, 8 (22%) have died (3 pulmonary vascular disease, 2 sudden death, 2 unknown causes and 1 complete heart block). Twenty other patients had a dysarrhythmia after surgery, and none of these died. Nine episodes of endocarditis occurred (11.4/10,000 patient years). Nine of 296 (3%) offspring had cardiac malformation. Most patients are in New York Heart Association class I, 57% attended college and 15% received an advanced degree. The data show good results for this group of patients operated on during an early era (1954 to 1960) of open cardiac surgery. They support the current trend toward operation in patients with ventricular septal defects at an early age and with low pulmonary vascular resistance. PMID- 1746433 TI - Comparison of transcranial Doppler ultrasound and transesophageal contrast echocardiography in the detection of interatrial right-to-left shunts. AB - Transesophageal contrast echocardiography is an effective but semiinvasive technique for the detection of interatrial right-to-left shunts. Transcranial Doppler ultrasound is an alternative noninvasive method, but may be limited by false-positive diagnoses due to intrapulmonary shunting. This study examined the accuracy of transcranial Doppler for the detection of shunt lesions. Transcranial Doppler of the right middle cerebral artery was performed simultaneously with transesophageal and transthoracic contrast echocardiography in 32 patients using agitated saline contrast during normal respiration and Valsalva. Transesophageal contrast echocardiography diagnosed an interatrial right-to-left shunt in 13 patients and intrapulmonary shunting in 6 patients. Transcranial Doppler identified all 13 interatrial right-to-left shunts and an intrapulmonary shunt in 3 of 6 patients. Absence of a shunt was confirmed by transcranial Doppler in 12 of 12 patients. Transcranial Doppler had a sensitivity of 100% (13 of 13), specificity of 100% (18 of 18) and accuracy of 100% (31 of 31) for prediction of an interatrial right-to-left shunt by transesophageal contrast echocardiography. In comparison, transthoracic contrast echocardiography had a sensitivity of 54% (7 of 13), specificity of 94% (17 of 18) and accuracy of 77% (24 of 31). Thus, transcranial Doppler is highly accurate for detection of an interatrial right-to left shunt and not compromised by physiologic intrapulmonary shunts, whereas transthoracic contrast echocardiography lacks sensitivity. Transcranial Doppler may be useful as an alternative to transesophageal study, where the primary indication for transesophageal echocardiography is exclusion of an interatrial right-to-left shunt. PMID- 1746434 TI - Effect of digoxin on ST-segment changes detected by ambulatory electrocardiographic monitoring in healthy subjects. AB - Digoxin causes false-positive ST depression during exercise stress testing, but it is unknown if digoxin produces ST depression during ambulatory electrocardiographic monitoring. Fifty healthy volunteers underwent both exercise stress testing and ambulatory electrocardiographic monitoring before and after 14 days of digoxin (0.25 mg/day) administration. Significant ST depression was defined as greater than or equal to 1 mm of horizontal or downsloping ST depression 80 ms after the J point lasting for greater than or equal to 60 seconds. During therapy, 13 subjects (26%) had at least 1 episode of ST depression and 5 subjects (10%) had multiple episodes of ST depression detected by ambulatory monitoring. Ten subjects (20%) had ST depression that occurred during exercise that was detected by both stress test and ambulatory monitoring. Three subjects (6%) had ST depression that was detected on the ambulatory recording only at times other than during the stress test. Stratification of demographic and clinical variables did not predict digoxin-induced ST depression. Thus, digoxin causes false-positive ST depression detected by ambulatory monitoring. The incidence is similar to that observed during stress testing, but also occurs at heart rates lower than that achieved during stress tests. Ambulatory electrocardiographic monitoring will be less useful in the noninvasive assessment of coronary artery disease in patients receiving digoxin. PMID- 1746435 TI - Two-dimensional contrast echocardiography in the detection and follow-up of congenital pulmonary arteriovenous malformations. AB - Pulmonary arteriovenous (A-V) malformation is frequently a manifestation of Osler Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia). We identified 14 patients (9 men and 5 women) with A-V malformation by contrast echocardiography; 10 patients with atrial right-to-left shunt served as control subjects. Agitated saline solution (10 ml) was injected through a peripheral vein during echocardiographic imaging. The delay in the appearance of microcavitations in the left atrium was measured (in number of frames) after right atrial appearance. The degree of left ventricular opacification was graded 1 to 4+ (where 4+ = intense left ventricular endocardial outline, and 1+ = minimal opacification). Results indicated patients with A-V malformation had a significant delay (p less than 0.001) in left atrial appearance of microcavitations compared with those with atrial right-to-left shunt (66 +/- 27 vs 21 +/- 7 frames, mean +/- 1 standard deviation). In the group with A-V malformation, abnormal blood gases were present in only 6 of 14 patients and chest x-ray was positive in 7. Pulmonary angiography was performed in 11 of 14 patients with positive contrast echocardiography, and all 11 had A-V malformation identified. In patients with 3 to 4+ left ventricular opacification (n = 8), large (greater than 5 mm feeding vessel) or multiple malformations were present, whereas patients with small or isolated malformation had 1 to 2+ left ventricular opacification. Balloon occlusion of malformations was performed in all 11 of these patients; repeat contrast echocardiography revealed significant diminution of right-to-left shunt in 9, and 2 required repeat embolotherapy for an additional previously undetected A-V malformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746436 TI - Cardiac myocytes and dendritic cells harbor human immunodeficiency virus in infected patients with and without cardiac dysfunction: detection by multiplex, nested, polymerase chain reaction in individually microdissected cells from right ventricular endomyocardial biopsy tissue. AB - Two hundred fifteen patients infected with human immunodeficiency virus (HIV) participated in a prospective longitudinal study of HIV-related heart disease. Evaluation included signal-averaged electrocardiography and echocardiography. Fifteen patients underwent endomyocardial biopsy, 5 had cardiovascular symptoms and 10 did not. Cardiac myocytes or dendritic cells were prepared by individual cell microdissection to sort them from other cell types such as interstitial cells or circulating blood elements. HIV proviral sequences were amplified in samples of 15 to 20 cells of each type by multiplex, nested, polymerase chain reaction and hybridized to 32P-labeled probes specific for regions within the gag and pol genes of HIV-1. The results showed the presence of HIV sequences in myocytes of 2 of 5 patients with cardiac symptoms and in 6 of 10 without. Thus, symptomatic HIV cardiomyopathy did not appear to be a direct consequence of the virus on myocardial cells. In dendritic cells, HIV sequences were detected in 5 of 5 patients with cardiac symptoms and in 8 of 10 with apparently normal ventricular function. Furthermore, dendritic cells were somewhat more numerous in the myocardium of symptomatic than asymptomatic patients. Our studies are the first to directly detect the HIV genome in purified cardiac myocytes from patients with and without cardiac dysfunction. Our findings do not support a direct role of the virus in myocardial dysfunction. However, the results do suggest that the interstitial dendritic cells may be involved in some manner in the development of cardiac dysfunction observed in HIV-infected patients. PMID- 1746437 TI - Moricizine (ethmozine HCl)--a new antiarrhythmic drug: is it unique? PMID- 1746438 TI - Medical, ethical and legal issues regarding thrombolytic therapy in the Jehovah's Witness. PMID- 1746439 TI - Coronary artery surgery in octogenarians. PMID- 1746440 TI - Prevalence and significance of ST-segment alternans during coronary angioplasty. PMID- 1746441 TI - Echocardiographic documentation of splenic anatomy in complex congenital heart disease. PMID- 1746442 TI - Frequency of positive blood cultures during transesophageal echocardiography. PMID- 1746443 TI - Prevalence of cardiac abnormalities early in the course of systemic lupus erythematosus. PMID- 1746444 TI - Focal myocardial necrosis associated with multiple sclerosis of the medulla. PMID- 1746445 TI - Thrombolytic therapy. Introduction. PMID- 1746446 TI - Overview of patency as an end point of thrombolytic therapy. AB - Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development. PMID- 1746447 TI - Thrombolysis, anticoagulation, and reocclusion. AB - Based on apparent higher recanalization rates of the infarct-related artery, preferential use of thrombolytic agents with high clot specificity has been proposed for treating patients with acute myocardial infarction. In the Thrombolysis in Myocardial infarction (TIMI-I) and European Cooperative Group studies, higher reperfusion rates were observed with alteplase compared with streptokinase, causing many to assume that the former would achieve a greater reduction in early hospital mortality. However, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-2) and its associated International Study Group failed to show any differences in 15-day mortality between these agents in more than 20,000 patients. This apparent lack of correlation between reperfusion rates and early mortality may be explained in part when one considers that recanalization or patency rates measured at a given point in time, such as 90 minutes after onset of therapy, fail to define the subsequent vessel status. Early reocclusion is the major reason for this and is a major limitation to the clinical efficacy of thrombolytic drugs. Following recanalization, residual fibrin-bound thrombin adherent to the site of arterial injury from plaque rupture strongly promotes rethrombosis. Although antiplatelet and antithrombin agents such as aspirin and heparin help to decrease rethrombosis, these agents are far from ideal. Thrombolytic agents that produce a significantly prolonged systemic thrombolytic state, such as streptokinase and anistreplase, are likely to result in less rethrombosis. Therefore, a systemic fibrinolytic state would appear to be an advantage rather than a disadvantage, particularly because the incidence of intracerebral hemorrhage does not appear to be greater with their use compared with agents producing less systemic fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746448 TI - Use of left ventricular function as an end point of thrombolytic therapy. AB - In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation. PMID- 1746449 TI - Importance of the pharmacological profile of thrombolytic agents in clinical practice. AB - Three thrombolytic agents are frequently used in the United States for treating patients with acute myocardial infarction: streptokinase, alteplase (tissue plasminogen activator [t-PA]), and anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]). A fourth agent, urokinase, is occasionally used but clinical experience is considerably more limited with this agent. Streptokinase, alteplase, and anistreplase differ in a number of pharmacologic properties, which include half-life, enzymatic efficiency, and induction of platelet aggregation; these differences may be clinically important. For example, anistreplase and alteplase have high affinity for fibrin and bind to intravascular thrombi after intravenous administration, which may result in higher clot specificity. Anistreplase has the longest half-life of the 3 agents and, therefore, can be administered conveniently and quickly. Alteplase has a shorter half-life and heparin is generally a necessary adjunctive agent. These differences can be clinically significant in various settings and application of such theoretical advantages is just beginning. PMID- 1746450 TI - Comparative safety of thrombolytic agents. AB - Three available thrombolytic agents, streptokinase, alteplase, and anistreplase, have been shown to have similar effects on preservation of left ventricular function and mortality reduction after acute myocardial infarction (AMI). The agents are, however, quite different with respect to their safety profiles. Clinical trials to date suggest that alteplase (tissue plasminogen activator) or anistreplase administration is associated with a high incidence of cerebral hemorrhage. In contrast, streptokinase is associated with a low rate of cerebral hemorrhage. Streptokinase and anistreplase are associated with a higher risk of allergic reaction when compared with alteplase. Hypotension is also more common with streptokinase and anistreplase, but occurs significantly with alteplase as well. Alteplase is associated with a lower reinfarction rate when compared with streptokinase and anistreplase. The Third International Study of Infarct Survival (ISIS-3), a direct comparison of 3 thrombolytic agents (streptokinase, anistreplase, and duteplase), may provide some insight regarding the safety of these agents. Because these agents have been shown to be equally effective, selection of an appropriate agent for an individual patient may depend more on assessment of the likelihood of an adverse event or other factors, such as cost or convenience of administration, rather than assessment of the probability of greater benefit with a particular agent. PMID- 1746451 TI - Comparative analysis of long-term mortality after thrombolytic therapy. AB - In patients with acute myocardial infarction, thrombolytic therapy has a demonstrable and favorable impact on a range of clinical indicators, including left ventricular function, infarct size, coronary arterial patency, and symptom relief. However, these indicators have not provided a reliable basis for the comparison of thrombolytic regimens; mortality provides the "gold standard." One year mortality obviates the differences in the timing of short-term comparisons (in-hospital, 30-day, or 5-week). In addition, late effects of differences in patency, including the impact of reocclusion, infarct healing, and remodeling, will be evident by 1 year. Meta-analysis of data from previous major mortality studies shows that differences in design and the overlap of confidence intervals of mortality studies suggest that no thrombolytic agent is superior in terms of short-term mortality. Long-term survival may provide a more meaningful basis for comparison of efficacy of the thrombolytic regimens. Long-term mortality has been evaluated for anistreplase in acute myocardial infarction in a composite analysis, similar to a meta-analysis. From the pooled life table analysis of all anistreplase studies, the odds reduction in mortality at 1 year was approximately 48%. PMID- 1746452 TI - Brief overview of the end points of thrombolytic therapy. AB - In addition to mortality, several measurable end points of thrombolytic therapy have been studied. These include coronary arterial patency, left ventricular function, reocclusion, reinfarction, and bleeding complications. Current wisdom dictates that recanalization of occluded arteries in the early phases of acute myocardial infarction should be attempted to preserve viable cardiac muscle, with the ultimate goal of decreasing mortality. Unfortunately, the number of patients eligible for thrombolytic therapy far exceeds the number receiving it, despite the clear benefits that have been demonstrated. PMID- 1746453 TI - Early detection of acute myocardial infarction by measurement of mass concentration of creatine kinase-MB. AB - The diagnostic sensitivity and performance of immunoenzymometric measurements of creatine kinase (CK)-MB mass concentrations in the early diagnosis of acute myocardial infarction (AMI) were examined and compared with the sensitivities and performances of CK and CK-MB activity, in the context of simultaneous measurements of CK, CK-MB activity, and CK-MB mass concentrations in serially drawn blood samples obtained immediately from 36 patients with AMI and 126 patients with chest pain on admission to the emergency room of the department of internal medicine. In the 36 patients with AMI, who were all admitted no later than 4 hours after the onset of chest pain, pathologic increase occurred significantly earlier in CK-MB mass than in both CK and CK-MB activity, with a median difference of 1 hour each. In patients coming to the emergency room (51 with AMI, 51 with angina pectoris and 24 with chest pain not related to coronary artery disease), CK-MB mass was the best diagnostic measurement for AMI of all markers tested (significantly higher efficiency, Youden index and likelihood ratio than both CK and CK-MB activity). Before initiating thrombolytic therapy, the sensitivity of CK-MB mass is significantly higher than CK-MB activity during the 0- to 6-hour period and significantly higher than CK activity during the 2- to 4-hour period after the onset of chest pain. Consequently, it is often possible to diagnose an AMI on the basis of increased CK-MB mass concentrations even at a time when CK and CK-MB activities are still within the reference interval. PMID- 1746454 TI - Comparative quantitative angiographic analysis of directional coronary atherectomy and balloon coronary angioplasty. AB - An attempt to assess the "utility" of directional atherectomy was made using a new quantitative angiographic index. This index can be subdivided into an initial gain component and a restenosis component. The initial gain index is the ratio between the gain in diameter during intervention and the theoretically achievable gain (i.e., reference diameter). The restenosis index is the ratio between the decrease at follow-up and the initial gain during the procedure. The net result at long-term follow-up is characterized by the utility index, which is the ratio between the final gain in diameter at follow-up and what theoretically could have been achieved. For this purpose, 30 coronary artery lesions were selected from a consecutive series of successfully dilated primary angioplasty lesions and were matched with the initial 30 successfully treated primary atherectomy lesions. Matching by location of stenosis and reference diameter resulted in 2 comparable groups with identical preprocedural stenosis characteristics. Atherectomy resulted in an increase in minimal luminal diameter 2 times larger than angioplasty (1.53 vs 0.77 mm; p less than 0.0001). However, at follow-up there was a significant decrease in minimal luminal diameter and a significant increase in percent diameter stenosis in the groups with atherectomy and angioplasty (1.69 +/- 0.58 vs 1.57 +/- 0.58 mm, p = not significant [NS], and 37 +/- 18 vs 47 +/- 18%, p = NS, respectively). The decrease in minimal luminal gain was more pronounced in the group with atherectomy than in that with angioplasty (0.92 +/- 0.69 vs 0.35 +/- 0.51 mm; p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746455 TI - Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group. AB - The effect of simultaneous infusions of low-dose recombinant tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) on coronary arterial thrombolysis was investigated in 23 patients treated within 6 hours (mean 2.6 +/- 1.1, range 1.2 to 5.9) of symptoms of an acute myocardial infarction. Infarct artery patency at 90 minutes was achieved in 16 (70%, 95% confidence limits of 0.47 to 0.87) of 23 patients after a 1-hour intravenous infusion of 20 and 16.3 mg of t-PA and scu PA, respectively. At 90 minutes, the fibrinogen concentration decreased from 369 +/- 207 to 316 +/- 192 mg/dl (p = not significant), while plasminogen decreased to 69 +/- 24% (p = 0.001) and alpha-2-antiplasmin to 77 +/- 24% (p = 0.001) of pretreatment values. Although no bleeding requiring termination of drug infusion or transfusion occurred, 1 patient with cerebrovascular amyloidosis had a fatal intracerebral hemorrhage. These findings suggest that combination therapy may allow substantial reductions in total thrombolytic doses while still achieving effective fibrin-specific coronary thrombolysis. PMID- 1746456 TI - Effectiveness of double bolus alteplase in the treatment of acute myocardial infarction. AB - Fifty-nine consecutive patients presenting within 6 hours of the onset of symptoms of an acute myocardial infarction were treated with 150 mg of soluble aspirin orally, and either 70 or 100 mg of alteplase divided into 2 intravenous bolus injections separated by 30 minutes. Dosage regimens were either 20 followed by 50 mg (group A), 50 followed by 20 mg (group B), or 50 followed by 50 mg (group C). Coronary angiography 60 minutes after the first bolus showed infarct related coronary artery patency (Thrombolysis in Myocardial Infarction score 2 or 3) in 13 of 16 (81%) patients in group A, 12 of 17 (71%) in group B, and 10 of 11 (91%) in group C (overall patency rate at 60 minutes: 35 of 44 [80%] patients; 95% confidence interval 68 to 91%). At 90 minutes, patency rates were 15 of 20 (75%) patients in both groups A and B, and 18 of 19 (95%) in group C (overall patency rate 48 of 59 [81%] patients; 95% confidence interval 72 to 91%). Residual thrombus was identified with the 90-minute angiogram in 7 patients in group A, 5 in group B, and 3 in group C. Although there was no statistically significant difference in patency between the 3 dosage regimens at either 60 or 90 minutes there was a trend toward increased patency and more complete thrombolysis at 90 minutes in group C. No episodes of bradyarrhythmia, hypotension or cerebrovascular bleeding were observed after double bolus therapy. There were 7 episodes (12%) of reocclusion, and 3 deaths (5%) within 1-month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746457 TI - Prognostic significance of silent myocardial ischemia in variant angina pectoris. AB - The present study investigates the prognostic significance of silent myocardial ischemia in variant angina. Forty-eight-hour Holter monitoring and coronary angiography were performed in 54 patients with transient ST elevation and no history of myocardial infarction admitted to the coronary care unit for worsening of symptoms. Coronary artery spasm was documented in most of these patients. Over the subsequent month, 20 patients (group 1) had a major coronary event (2 died, 6 had nonfatal myocardial infarction and 12 had urgent coronary revascularization), and the remaining 34 patients (group 2) had a good clinical outcome. From 2,578 hours of recording, 547 ischemic episodes were identified of which only 9% were associated with angina. The mean daily number of ST elevation in group 1 was similar to that in group 2 (4.8 +/- 5.1 vs 4.1 +/- 4.6; p = not significant). Conversely, the mean daily duration of such ischemic episodes was consistently greater in group 1 than in 2 (79 +/- 36 vs 37 +/- 25 minutes; p less than 0.005). The occurrence of greater than or equal to 1 long-lasting (greater than or equal to 10 minutes) episode of ST elevation was observed in 18 of 20 patients in group 1 (sensitivity 90%), but only in 4 of 34 in group 2 (specificity 88%). Significant coronary atherosclerosis (greater than 50% stenoses) was found at angiography in 18 of 20 patients in group 1, and in 18 of 34 in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746458 TI - Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal's angina pectoris. AB - In 30 consecutive patients with Prinzmetal's angina pectoris, the antiischemic effect of felodipine, a new long-acting vasoselective calcium antagonist, administered at doses of 10 and 20 mg once daily was compared with that of the well-established therapeutic regimen with nifedipine administered at a dose of 20 mg 4 times daily. Twenty-four-hour Holter monitoring was performed during a 2-day placebo run-in and at the end of each of 3 consecutive 6-day periods during which the 3 active treatments were administered in randomized sequence. Three patients withdrew, whereas 27 completed the study. The therapeutic regimens tested proved to be similarly effective; primary end points (ischemic episodes recorded by Holter monitoring, and anginal attacks reported on diary cards) occurred in 5 patients (19%) during nifedipine treatment, and in 7 (26%) and 3 (11%) during felodipine treatment with 10 and 20 mg, respectively (p = not significant). The distribution of residual ischemic episodes demonstrated that treatment with felodipine once daily provides 24-hour antiischemic protection. Twenty-six patients were followed up with 20 mg of felodipine once daily for a mean of 6 +/- 5 months, and 21 of them (81%) remained free of symptoms and Holter-recorded ischemic attacks. It is concluded that for Prinzmetal's angina pectoris, 24-hour antiischemic protection may be achieved with administration of felodipine once daily. The availability of a simplified therapeutic approach may constitute a real advantage in terms of patient compliance and improving the quality of life. PMID- 1746459 TI - Effects of daily high-intensity exercise on myocardial perfusion in angina pectoris. AB - Forty male patients with chronic stable angina pectoris and no prior myocardial infarction were studied by planar thallium scintigraphy with use of circumferential profile analysis. Ischemic defects were assessed by measuring degrees of circumference involved and area of defect. Data were collected for 3 vascular regions in each of 3 views (anterior, 45 degrees and 65 degrees left anterior oblique projection). Patients were then randomized to exercise and control groups, the former training for a period of 1 year using the Canadian Airforce plan for physical fitness. After 1 year, both groups were restudied. Exercise training produced a 34% reduction in degrees of ischemia overall (p less than 0.02), the most significant change being seen on the anterior view (72 degrees +/- 59 degrees before vs 30 degrees +/- 35 degrees after training). Regional analysis showed markedly improved perfusion anterolaterally and apically on the anterior view and anteroseptally on the 65 degrees left anterior oblique view. These improvements support the hypothesis that exercise training improves myocardial perfusion by enhanced collateral function. PMID- 1746460 TI - Silent versus symptomatic ischemia during a thallium-201 exercise test. AB - One hundred thirty-four patients with redistribution on a thallium-201 exercise test who did not experience angina (group 1) were compared with 134 patients also having redistribution who had angina during the test (group 2). The groups were matched by age, sex, and peak exercise heart rate. Although patients in both groups achieved an equivalent exercise level, patients in group 1 had less frequent (53 vs 71%, p less than 0.005) and less severe (0.15 +/- 0.13 vs 0.20 +/ 0.13 mV, p less than 0.005) ischemic ST-segment depression. Group 1 also had less ischemic thallium-201 images in terms of the number of redistributing defects, the severity of the worst redistributing defect, and an ischemic index composite of both extent and severity. Patients in group 1 were less likely to undergo early revascularization (12 vs 29%, p less than 0.005), but in the remaining patients the occurrence of adverse cardiac events was similar (21% vs 29%, p = not significant). By multivariate analysis, only the ischemic index correlated with early revascularization in group 1 (p = 0.0017), whereas the percent maximal predicted heart rate correlated best in group 2 (p = 0.0003). In group 1 the ratio of lung/heart thallium-201 uptake correlated best with an outcome of nonfatal myocardial infarction or cardiac death (p = 0.0024); in group 2 the presence of fixed left ventricular dilatation did (p = 0.0022). Thus, patients with exercise-induced thallium-201 redistribution without angina have less ischemia than patients experiencing angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746461 TI - Experience with low-dose intracoronary recombinant tissue-type plasminogen activator for nonacute total occlusions before percutaneous transluminal coronary angioplasty. AB - The primary success rate for angioplasty of total occlusions is significantly worse than for subtotal lesions. Pharmacologic recanalization of total occlusions before angioplasty has the potential to improve the primary success rate. To determine the ability of recombinant tissue-type plasminogen activator (rt-PA) to recanalize occlusive thrombi before elective percutaneous transluminal coronary angioplasty, 12 patients with total occlusions, 100% obstruction and Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow, and 5 with functional total occlusions, severe stenoses and TIMI grade 1 flow received an intracoronary infusion of rt-PA. The first 10 patients received 0.2 mg/min for 90 minutes, and the next 7 patients received 0.4 mg/min for 60 minutes. Flow improved by greater than or equal to 1 TIMI grade in 11 patients. Mean TIMI flow improved from 0.3 +/ 0.5 to 1.5 +/- 1.2 (p less than 0.0001). There was a significant improvement in severity of stenosis after rt-PA infusion by both digital caliper (99 +/- 2 vs 84 +/- 16%; p less than 0.0001) and quantitative videodensitometric area assessment (99 +/- 3 vs 94 +/- 6%; p less than 0.004). Angioplasty was successful in 16 of 17 patients (94%). There were 2 out-of-laboratory abrupt closures at 4 days; both were medically treated and 1 had a small myocardial infarction. Only 1 patient had a bleeding complication significant enough to need a transfusion. It is concluded that low-dose intracoronary rt-PA is effective at lysing thrombi less than 3 weeks old. This approach warrants further investigation since it may significantly improve the primary success rate of percutaneous transluminal coronary angioplasty in patients with occlusive thrombus. PMID- 1746462 TI - Comparison of angiographic findings and demographic variables in patients with coronary artery disease presenting with acute pulmonary edema versus those presenting with chest pain. AB - One hundred nineteen patients admitted to the coronary care unit with pulmonary edema were retrospectively reviewed to identify the demographic characteristics and underlying cardiac disorders of this population. The patients with pulmonary edema were compared with 119 patients admitted to the coronary care unit with chest pain. Cardiac catheterization in 71 patients with pulmonary edema and 93 with chest pain showed left main and 3-vessel coronary artery diseases to be equally common in both groups, although anginal pain was infrequent in patients with pulmonary edema (n = 28, 24%). Left ventricular function was reduced in the patients with pulmonary edema compared with those with chest pain (mean ejection fraction 42 vs 59%; p less than 0.001). More patients with pulmonary edema were black, and had diabetes and preexisting hypertension than those with chest pain. The results of cardiac catheterization were the same for black and white patients with pulmonary edema. In conclusion, patients with pulmonary edema have a high incidence of cardiac disease, and pulmonary edema may be 1 manifestation of silent myocardial ischemia. Important demographic differences exist between patients admitted with pulmonary edema and those who present with chest pain. PMID- 1746463 TI - Significance of signal-averaged P-wave changes during exercise in patients with coronary artery disease and correlation with angiographic findings. AB - The maximal P-wave duration in all time-aligned leads, and the maximal P-wave amplitude in leads V5 and V6 were measured on a 12-lead, signal-averaged electrocardiogram during the recovery period of an exercise stress test (EST). The study group consisted of 75 patients with coronary artery disease (CAD) documented by greater than or equal to 50% diameter stenosis in 1 or more arteries and a control group of 47 subjects, 15 of them young volunteers and 32 with no or minimal coronary atherosclerosis and normal left ventricular function. All subjects underwent a symptom limited EST, with use of the Ellestad protocol. Signal-averaged P waves recorded before exercise, and for the first 6 minutes in recovery were measured using a 5x magnifier. The mean P duration before exercise in the control group was 107 +/- 16 ms (+/- 1 standard deviation) and 111 +/- 15 ms at the third minute of recovery, (p less than 0.001). In patients with CAD it was 112 +/- 12 and 129 +/- 19 ms (+/- 1 standard deviation), p less than 0.001, respectively. Differences in P-wave duration were found to be statistically significant (p less than 0.001) throughout recovery in the group with CAD when compared with control and maximal values at the third minute. The increase in P wave duration (greater than or equal to 20 ms) was used as an additional parameter to exercise-induced ST-segment depression, ST elevation, or anginal pain for the test interpretation. The sensitivity increased from 57 to 75% and the specificity decreased from 85 to 77%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746464 TI - Assessment of medial thinning in atherosclerosis by intravascular ultrasound. AB - This study investigated the in vitro (40 MHz) and in vivo (30 MHz) feasibility of intravascular ultrasound to document the influence of atherosclerotic lesions on the typical 3-layered appearance of muscular arteries. The in vitro images of 39 arteries were compared with the corresponding histologic sections. Media and lesion thickness were measured at the areas of minimal and maximal lesion thickness. The median media thickness was 0.8 mm in the absence of a lesion, decreasing to 0.3 mm in the area of maximal atherosclerosis. The ultrasonic data correlated closely with histologic measurements (0.6 and 0.3 mm, respectively). The in vivo study was performed in 29 patients undergoing coronary or peripheral vascular procedures. A total of 150 still-frames were selected for quantitative analysis. The median media thickness was 0.6 mm in the absence of a lesion, decreasing to 0.1 mm in the area with maximal atherosclerosis. This study revealed that intravascular ultrasound imaging accurately determines that media thickness of muscular arteries is inversely related to lesion thickness. In vitro data, verified with histology, can be translated to humans in vivo. PMID- 1746465 TI - Coronary hemodynamics and coronary flow reserve after intracoronary diltiazem in humans. AB - To analyze the effect of the calcium antagonist diltiazem on coronary hemodynamics, epicardial coronary artery diameter, coronary blood flow and coronary blood flow velocity were assessed at baseline and after a 0.5 mg intracoronary bolus of diltiazem in nonstenotic coronary arteries of awake humans. Patients (n = 20) were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 microgram/kg/min infusion; n = 10), and coronary flow reserve was measured before and after administration of diltiazem. There were significant increases in epicardial coronary artery diameter (10%; p = 0.0001) and coronary blood flow (30%; p = 0.0001) in all patients after administration of diltiazem. Whereas basal coronary blood flow velocity increased only slightly (7%; p = not significant), there was a significant decrease in coronary flow reserve (10%; p = 0.004). Increases in coronary diameter and blood flow after diltiazem were comparable in patients pretreated with placebo or nitrates. However, the decrease in coronary flow reserve was significant only in patients pretreated with placebo (19%; p = 0.0008). This reduction in coronary flow reserve could be due to "raising the floor" (increased baseline coronary blood flow) or "lowering the ceiling" (reduction of maximal coronary blood flow). PMID- 1746466 TI - Regional myocardial perfusion and metabolism assessed by positron emission tomography in children with Kawasaki disease and significance of abnormal Q waves and their disappearance. AB - To clarify the significance of newly appearing abnormal Q waves and their disappearance in patients with Kawasaki disease, regional myocardial perfusion and glucose metabolism at rest in the fasting condition were assessed by positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose (FDG), and regional wall motion by left ventriculography in regions with persistent and transient abnormal Q waves in 14 patients. PET identified 3 groups of abnormal myocardial segments: segments with hypoperfusion without increased FDG uptake, those with hypoperfusion and increased FDG uptake, and those with normal perfusion and increased FDG uptake. Almost all the segments with persistent or transient abnormal Q waves had abnormal PET findings. PET demonstrated evidence of metabolic activity in 57% of segments with persistent abnormal Q waves and 67% of those with transient abnormal Q waves. Regional wall motion, scored from 0 (normal) to 4 (dyskinesia), was not significantly different between segments with persistent and transient abnormal Q waves (2.3 +/- 1.3 vs 2.2 +/- 1.2). The persistence of abnormal Q waves on serial electrocardiograms was significantly shorter in metabolically active than in inactive segments (19 +/- 17 vs 92 +/- 27 months). In conclusion, in patients with Kawasaki disease, the new appearance of abnormal Q waves is a reliable clue to the presence of ischemic myocardial injury and a high proportion of them are associated with metabolically active myocardial regions. The disappearance of abnormal Q waves does not necessarily mean the normalization of regional myocardial perfusion, metabolism or function, and their early disappearance may imply "viability" in the associated myocardial region. PMID- 1746467 TI - Usefulness of the total cholesterol to high-density lipoprotein cholesterol ratio in predicting angiographic coronary artery disease in women. AB - To investigate the relation between lipids and angiographic coronary artery disease (CAD) in women, fasting lipid profiles were obtained on 108 women undergoing coronary angiography (group I). CAD, defined as greater than or equal to 25% luminal diameter narrowing in a major coronary artery, was present in 57 (53%). Neither serum total cholesterol nor triglyceride levels correlated with the presence of CAD. Mean total/high-density lipoprotein (HDL) cholesterol ratio was higher among women with than without CAD (5.5 +/- 0.3 vs 4.2 +/- 0.2, p less than 0.0001). Multiple regression analyses identified a higher total/HDL cholesterol ratio as the variable most predictive of the presence (p less than 0.001), extent (number of narrowed arteries) (p less than 0.0001), and severity (% maximum stenosis) (p less than 0.001) of CAD. Age and lack of estrogen use were also independently associated with the presence of CAD, age and low-density lipoprotein cholesterol level were additional indicators of extent, and age was the only other discriminator of severity of CAD. In 56 women with total cholesterol less than 200 mg/dl (group II), mean total/HDL cholesterol ratio was higher in women with (n = 24) than without CAD (4.3 +/- 0.2 vs 3.5 +/- 0.2, p = 0.01). Higher total/HDL cholesterol ratio was the variable most predictive of the presence of CAD (p = 0.01), and the lone variable associated with severity (p less than 0.001) after adjustment for other risk factors. Age was independently associated with presence and extent, and hypertension was also independently related to extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746468 TI - Radiofrequency catheter ablation of accessory pathways: a learning experience. AB - Success rates of approximately 90% have recently been reported with radiofrequency catheter ablation of accessory pathways. This study determined whether this success could be repeated using a conservative approach generally limiting fluoroscopy time to 1 hour. Consecutive patients referred for management of arrhythmias associated with accessory atrioventricular pathways were included over a 9-month period. Ablation was attempted in 75 patients with 84 pathways. Overall success rate (including second attempts in 9 patients) was 60 of 84 accessory pathways (71%). Success rates for the first 3 months (n = 23) were 52%, the second 3 months (n = 23) 60% and the last 3 months (n = 38) 90%. Success rate varied with pathway location, with left lateral pathways having the best early success rates. Mean fluoroscopy time for successful procedures of 33 +/- 21 minutes was shorter than the time for unsuccessful procedures of 63 +/- 24 minutes (p = 0.001). There were no major complications and no patients with successful procedures (n = 53) have had recurrence of accessory pathway conduction or reciprocating tachycardia (follow-up 1 to 10 months). A conservative approach can yield success rates approaching 90% in a short time. The absence of major complications supports earlier reports suggesting that radiofrequency catheter ablation of accessory pathways is a reasonable first-line therapy in the Wolff-Parkinson-White syndrome. PMID- 1746469 TI - Reduction in medical care cost associated with radiofrequency catheter ablation of accessory pathways. AB - The cost of definitive therapy was compared in 25 patients who underwent radiofrequency catheter ablation of accessory pathways in 1990 and 25 patients who underwent surgical ablation of accessory pathways in 1989. In the radiofrequency group, 23 of 25 patients had a single accessory pathway and the remaining 2 patients each had 2 accessory pathways. In the surgical group, 20 patients had a single accessory pathway and 5 patients each had 2 accessory pathways. The success rate was 96% in each group. The mean duration of hospitalization was 3 +/- 1 days in the radiofrequency group and 9 +/- 4 days in the surgical group (p less than 0.0001). All the cost data are expressed in fiscal year 1990/1991 dollar values. The total cost of therapy in the radiofrequency group was $14,919 +/- $6,740 compared with $53,265 +/- $12,755 in the surgical group (p less than 0.0001). The cost of radiofrequency ablation consisted of a hospital charge of $7,753 +/- $3,472 and physician fees of $7,166 +/- $3,439. The hospital charge included charges for use of the electrophysiology laboratory, hospital stay, electrocardiograms, echocardiograms and blood studies. The cost of surgery consisted of a hospital charge of $37,708 +/- $10,179 and physician fees of $15,557 +/- $3,149. The hospital charge in the surgical group included the costs of a baseline electrophysiology study, in-hospital care and a follow-up office visit. In conclusion, radiofrequency catheter ablation of accessory pathways results in a dramatic reduction in the cost of definitive therapy in patients with the Wolff-Parkinson-White syndrome. PMID- 1746470 TI - Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients with congestive heart failure secondary to coronary artery disease. AB - Before heart rate (HR) variability can be used for predictive purposes in the clinical setting, day-to-day variation and reproducibility need to be defined as do relations to mean HR. HR variability and mean HR were therefore determined in 2 successive 24-hour ambulatory electrocardiograms obtained from 33 normal subjects (age 34 +/- 7 years, group I), and 22 patients with coronary disease and stable congestive heart failure (CHF) (age 59 +/- 7 years, group II). Three measures were used: (1) SDANN (standard deviation of all mean 5-minute normal sinus RR intervals in successive 5-minute recording periods over 24 hours); (2) SD (the mean of the standard deviation of all normal sinus RR intervals in successive 5-minute recording periods over 24 hours); and (3) CV (coefficient of variation of the SD measure), a new measure that compensates for HR effects. Group mean HR was higher and HR variability lower in group II than in group I (80 +/- 10 vs 74 +/- 9 beats/min, p less than 0.04). Mean group values for HR and HR variability showed good correlations between days 1 and 2 (mean RR, r = 0.89, 0.97; SDANN, r = 0.87, 0.87; SD, r = 0.93, 0.97; CV, r = 0.95, 0.97 in groups I and II, respectively). In contrast, considerable individual day-to-day variation occurred (group I, 0 to 46%; group II, 0 to 51%). Low HR variability values were more consistent than high values. SDANN and SD correlated moderately with HR in both groups (r = 0.50 to 0.64). The CV measure minimizes HR effects on HR variability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746471 TI - Comparison of transthoracic and transesophageal echocardiography for assessment of left-sided valvular regurgitation. AB - To compare transthoracic and transesophageal echocardiography in the clinical assessment of left-sided valvular regurgitation, 118 patients who underwent both transesophageal and transthoracic echocardiographic studies within a 24-hour period were included in this study. Presence or absence of aortic regurgitation was identified concordantly by both techniques in 93 patients (79%). Complete agreement between both techniques was found in 88 patients (75%). Presence or absence of mitral regurgitation was identified concordantly by both techniques in 89 patients (75%). Complete agreement in grade was found in only 74 patients (63%). Twenty-nine patients (25%) had mitral regurgitation detected by transesophageal echocardiography, but not by transthoracic echocardiography. Four of these patients (14%) had significant (2 to 3+) mitral regurgitation. Differences between transesophageal and transthoracic echocardiography do not appear to be clinically important in patients with aortic regurgitation. In mitral regurgitation, significant differences exist between these 2 techniques, with transesophageal echocardiography being much more sensitive. PMID- 1746472 TI - Pulmonary valve-moderator band distance and association with development of double-chambered right ventricle. AB - Double-chambered right ventricle (DCRV), a form of right ventricular outflow obstruction that sometimes accompanies a ventricular septal defect (VSD), is associated with superior and rightward displacement of the septal insertion of the moderator band. It was hypothesized that this superior displacement is present and identifiable by echocardiography in patients with a VSD even before right ventricular outflow tract obstruction develops. Eight patients who had a previous echocardiographic study showing a VSD alone were echocardiographically diagnosed as having DCRV. Their initial echocardiographic studies were reviewed, and superior displacement of the moderator band was quantified by measuring the distance between the pulmonary valve and moderator band, normalized to tricuspid anulus diameter. These measurements were compared with those from the initial studies of the following 3 other groups: (1) an age-matched group of 10 patients with no structural heart disease; (2) an age-matched group of 10 patients with a VSD who did not develop DCRV; and (3) a group (not age-matched) of 10 patients with VSD and DCRV in whom subpulmonary obstruction was present on the initial study. The 8 patients who eventually developed subpulmonary obstruction had significant superior displacement of the moderator band at the time of their initial echocardiogram compared with that of the 2 age-matched control groups (p less than 0.01). In contrast, there was no significant difference in moderator band displacement between these patients and the 10 with DCRV who already had right ventricular outflow obstruction at their initial study (p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746473 TI - Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. AB - Ten patients with pulmonary hypertension associated with diffuse systemic sclerosis (1 patient), the CREST syndrome (calcinosis cutis, Reynaud's phenomenon, esophageal dysmotility, sclerodactyl, telangiectasia) (6 patients) and mixed connective tissue disease (3 patients) were studied to assess the effect of oral nifedipine on pulmonary and systemic hemodynamics. Each patient underwent right-sided cardiac catheterization just before nifedipine administration. Thereafter, oral nifedipine was administered in 10 mg increments every 90 minutes until pulmonary vascular resistance normalized or a total dose of 30 mg was achieved. Hemodynamic measurements were obtained at 30-minute intervals for 3 hours, then hourly for 9 hours (acute study). Hemodynamic studies were repeated 3 to 6 months after the initial catheterization with the minimum dose of oral nifedipine (administered every 8 hours) required to achieve maximal reduction of pulmonary vascular resistance in the acute study (long-term study). In the acute study, oral nifedipine produced a significant decrease in mean pulmonary vascular resistance from 6.3 +/- 3.8 to 4.3 +/- 3.6 U (p less than 0.001). Similar changes in pulmonary vascular resistance were noted in the long term study (n = 6). The results indicate that oral nifedipine is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease. PMID- 1746474 TI - Echocardiographic assessment of left ventricular function and wall motion at high altitude in normal subjects. AB - To understand the effects of high-altitude hypoxia on cardiac function and the change in cardiac function during high-altitude acclimatization, precise studies were first performed at greater than 5,000 m of altitude in Himalaya by 2 dimensional echocardiography. In addition to examining well-known indexes of cardiac function, the centerline method was used to assess regional wall motion, which has not been examined under conditions of high-altitude hypoxia. The subjects were 11 climbing members (aged 21 to 43 years) of the Kyoto University Medical Research Expedition of Xixabangma (8,027 m) in 1990. Examinations were performed at sea level, at the base camp (5,020 m), and twice at the advanced base camp (5,650 m). Heart rate, left ventricular (LV) end-diastolic volume, cardiac output, mean rate of circumferential fiber shortening, ejection fraction, % fractional shortening, and regional LV wall motion were measured. At high altitude, heart rate increased to 136% of the sea level value, but gradually decreased in the degree of increment at the early and late advanced base camp measurements. LV end-diastolic volume decreased significantly by 70%. At base camp there were significant increases in ejection fraction, mean rate of circumferential fiber shortening, and % fractional shortening, which showed little change during the long-term stay at high altitude. Regional wall motion at high altitude (measured by the center-line method) decreased at the septal wall and increased at the posterolateral wall. These results demonstrate that: (1) LV cardiac performance at high altitude is enhanced significantly in spite of reduced preload. After good acclimatization, cardiac performance remains augmented, but there is a tendency to decrease the degree of augmentation. (2) In regional LV wall motion, septal wall motion is impaired, but LV posterolateral wall motion shows a compensatory increase. PMID- 1746475 TI - Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest. AB - Syndrome X is characterized by an abnormal vasomotility of coronary microvessels. It is unknown whether the presence of an ischemic-like pattern in the electrocardiogram at rest (T-wave inversion) reflects a more severe vasomotion disturbance. Changes in coronary sinus flow (thermodilution) and epicardial vessel diameter (quantitative angiography) during adrenergic activation were measured with a standard cold pressor test in patients with syndrome X whose electrocardiogram at rest was normal (group 1: 17 patients) or showed stable, symmetrically inverted T waves (group 2: 22 patients). Cold pressor test increased mean blood pressure and rate-pressure product to a similar extent in both groups, increased coronary sinus flow in group 1 (88 +/- 29 to 119 +/- 36 ml/min; p less than 0.05) and not in group 2 (109 +/- 37 vs 104 +/- 36 ml/min; p = not significant), and decreased coronary resistance in group 1 (1.38 +/- 0.42 to 1.19 +/- 0.38 mm Hg/ml/min; p less than 0.05) and augmented it in group 2 (1.06 +/- 0.32 to 1.28 +/- 0.43 mm Hg/ml/min; p less than 0.02). During cold stimulus, the proximal and middle segments of epicardial arteries showed negligible changes in their lumen, whereas the distal segment dilated in group 1 (1.81 +/- 0.27 to 2.01 +/- 0.32 mm; p less than 0.05) and constricted in group 2 (1.82 +/- 0.12 to 1.62 +/- 0.20 mm; p less than 0.05). Differences in coronary hemodynamic and angiographic responses between the groups were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746476 TI - Cost-effectiveness analysis of the use of digoxin immune Fab (ovine) for treatment of digoxin toxicity. AB - Each year many people have digitalis toxicity severe enough to require extensive hospital treatment. Digoxin immune Fab[ovine]-Fab fragments (Digibind) have been shown to reverse digitalis toxicity and substantially reduce the risk of death. Data were used from uncontrolled studies of patients treated with Fab fragments as well as clinical, medical care and pharmacokinetic data from symptomatically treated patients to derive estimates of the difference in clinical outcomes and medical care costs when treating with this new drug. Estimates are derived separately for treatment of patients with toxicity that is immediately life threatening and patients whose manifestations are not immediately life threatening. Treatment with Fab fragments reduces the probability of dying more for the seriously toxic than for the less seriously toxic patient. Such treatment is generally associated with an increase in total medical care costs for the seriously toxic patients because more of them survive the toxic episode and require additional medical care before discharge from the hospital. For these patients, the estimated cost per life-year saved is between $1,900 and $5,400. When Fab fragments are used to treat less seriously toxic patients, total medical care costs decrease because of an estimated decreased number of days in the coronary care unit and decreased use of pacemakers and other aggressive treatments. PMID- 1746477 TI - Limitations of testing methods for evaluation of dual chamber versus single chamber adaptive rate pacing. PMID- 1746478 TI - Usefulness of coronary angiography in patients requiring repeat cardiac valve surgery. PMID- 1746479 TI - Effectiveness of balloon percutaneous valvuloplasty for stenotic bioprosthetic valves in different positions. PMID- 1746480 TI - Clinical spectrum of venous thrombi in the Fontan patient. PMID- 1746481 TI - Clinical characteristics of patients with acute pulmonary embolism. PMID- 1746482 TI - Lymphoproliferative disorder early after cardiac transplantation. PMID- 1746483 TI - Appearance of or persistence of severe mitral regurgitation without left ventricular outflow obstruction after partial ventricular septal myotomy-myectomy in hypertrophic cardiomyopathy. PMID- 1746484 TI - Alkaline paper and preserving the record. PMID- 1746485 TI - Sorting out heightened interactions between platelets and von Willebrand factor. "IIB or not IIB?" is becoming an increasingly answerable question in the molecular era. PMID- 1746486 TI - DNA measurement by image analysis of paraffin-embedded breast carcinoma tissue. A comparative investigation. AB - Measurement of cellular DNA content may provide useful prognostic information in several human neoplasms. The DNA content by image analysis of fresh tissue has been compared with flow cytometry with good correlation, but the use of paraffin embedded tissue for image analysis has not been studied widely. This study reports the DNA content of 54 breast carcinomas and compares the results of image analysis of paraffin-embedded tissue and results of image analysis and flow cytometry of corresponding fresh tumors. Image analysis of paraffin blocks and fresh tumors showed comparable results in 51 tumors (94%), whereas 47 tumors (87%) were similar by all three methods. The DNA indices from image analysis of fresh and paraffin-embedded tumors showed significant correlation by linear regression analysis (r = 0.96; P less than 0.001). Discordances between image analysis of fresh and paraffin-embedded tumors are the result of technical problems, such as staining and tissue preservation. Discordances between image analysis and flow cytometry reflect the advantages and pitfalls of the two techniques. These data suggest that image analysis of paraffin-embedded tissue is a viable technique that will permit the performance of retrospective studies with long-term follow-up data for the evaluation of the prognostic significance of DNA content. PMID- 1746487 TI - Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases. AB - The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Bottcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation. PMID- 1746488 TI - The rapid differentiation of type IIb von Willebrand's disease from platelet-type (pseudo-) von Willebrand's disease by the "neutral" monoclonal antibody binding assay. AB - The differentiation of type IIb von Willebrand's disease from other variants of von Willebrand's disease, especially platelet-type (pseudo-) von Willebrand's disease, poses a significant clinical problem because, although they are similar in the clinical and diagnostic laboratory settings, the therapy of type IIb von Willebrand's disease is different from the therapy of platelet-type von Willebrand's disease. This discrimination has required cumbersome assays using fresh platelet-rich plasma that often yielded equivocal results. Because it was shown by other researchers that type IIb von Willebrand factor binds to normal platelets with increased avidity at low concentrations of ristocetin, it was reasoned that von Willebrand factor from patients with type IIb von Willebrand's disease would also bind to formalin-fixed washed platelets at low concentrations of ristocetin. Using the radiolabeled "neutral" monoclonal antibody AVW1 to label plasma von Willebrand factor, the binding of von Willebrand factor to formalin fixed washed platelets was studied as a function of ristocetin concentration. These studies demonstrated that the 125I-AVW1 von Willebrand factor from 13 patients with type IIb von Willebrand's disease binds to formalin-fixed washed platelets at significantly lower concentrations of ristocetin than plasma von Willebrand factor from 18 normal individuals, 3 patients with platelet-type von Willebrand's disease and 8 patients with other variant forms of von Willebrand's disease. This radiolabeled "neutral" monoclonal antibody technique provides a rapid, simple method for the differentiation on frozen plasma samples of type IIb von Willebrand's disease from platelet-type and other variants of von Willebrand's disease. PMID- 1746489 TI - The estimation of whole blood viscosity by a porous bed method. AB - A significant impediment in determining the relative contribution of whole blood viscosity to the pathogenesis of cardiovascular and cerebrovascular disease has been the lack of an uncomplicated method to measure whole blood viscosity. To address this problem, a simplified porous bed viscometer has been developed to measure whole blood viscosity. Whole blood is passed through a porous bed of branching channels with a mean pore diameter of 69.6 +/- 20.2 microns and an estimated mean shear rate of 19.6 seconds-1. The effects of sample collection, sample storage, and temperature are described. The mean whole blood viscosity of 242 healthy persons was 22.7 +/- 5.3 seconds, which, when corrected to centipoise using Darcy's equation, corresponds to an apparent viscosity of 5.7 +/- 1.3 cp. There was a significant difference in the whole blood viscosity of normal men and women related to their different packed cell volumes. Platelets and granulocytes influenced whole blood viscosity in proportion to their contribution to the total packed cell volume. Fibrinogen levels did not significantly influence measured whole blood viscosity, which is consistent with the disaggregating conditions and the mean shear rate of the instrument. The porous bed viscometer is a convenient means to measure whole blood viscosity and it should be useful as a screening test for clinical and epidemiologic studies. PMID- 1746490 TI - Diversity of organ site involvement among malignant lymphomas of mucosa associated tissues. AB - Fifteen cases of low-grade B-cell lymphoma involving unusual extranodal sites have been studied in comparison to cases reported or observed arising in typical mucosa-associated lymphoid tissues. In every case, histopathologic features conformed to those characteristic for lymphomas of mucosa-associated lymphoid tissues, including the production of lymphoepithelial complexes. Immunoglobulin light chain restriction was demonstrated by immunocytochemistry in 14 cases. Sites of involvement included the breast (6), skin (5), kidney (1), prostate (1), gallbladder (1), and uterine cervix (1). In three cases there was simultaneous or previous lymphoma of mucosa-associated lymphoid tissues identified in a more common mucosal site. It is concluded that the unifying concept of lymphomas of mucosa-associated lymphoid tissues applies to extranodal organs less commonly associated with mucosa-associated lymphoid tissues, as well as to those mucosal organ sites described in earlier series. PMID- 1746491 TI - Immunoglobulin gene rearrangement in abnormal lymph node hyperplasia. AB - The histologic designation "abnormal lymphoid hyperplasia" is applied to lymph nodes demonstrating varying degrees of architectural effacement and/or cytologic atypia. Although some of these cases may be suggestive of non-Hodgkin's lymphoma, a definitive diagnosis is not possible despite careful morphologic and immunophenotypic studies. Because the demonstration of immunoglobulin and T-cell receptor gene rearrangements by Southern blot analysis provides a sensitive marker of lineage and clonality in lymphoid malignant conditions, the frequency with which such gene rearrangements could be identified in abnormal hyperplasia and their significance were studied. DNA samples from lymph node biopsy samples of 11 patients with abnormal lymphoid hyperplasia were analyzed for rearrangements of immunoglobulin and T-cell receptor genes by Southern blot hybridization. Six of these patients had monoclonal B-cell populations identified by immunoglobulin gene rearrangements; all were found subsequently to have non Hodgkin's lymphoma by repeated biopsy from 8 days to 46 months later. Two patients with negative Southern blot studies also developed lymphoma, one a T cell non-Hodgkin's lymphoma and one a cutaneous B-cell non-Hodgkin's lymphoma. Three patients without detectable gene rearrangements showed no evidence of malignant lymphoma at 36-, 45-, and 60-month follow-up evaluations. Southern blot analysis thus identified monoclonal B-cell lymphoid populations in a subset of patients with abnormal lymphoid hyperplasia; the presence of clonal immunoglobulin gene rearrangement predicted progression to overt non-Hodgkin's lymphoma. PMID- 1746492 TI - Evaluation of four coagulation tests to detect plasma lupus anticoagulants. AB - Lupus anticoagulant was detected in 205 newly diagnosed, untreated patients with systemic lupus erythematosus by the following tests: kaolin clotting time, activated partial thromboplastin time, plasma prothrombin time, and, in the last 99 patients, by dilute Russell's viper venom time. In 10 patients, lupus anticoagulant was detected by kaolin clotting time prolongation, corrected by inosithin but not by normal plasma; 12 and 6 of them had prolonged activated partial thromboplastin time and partial plasma prothrombin time, respectively. Only 10 patients had a history of recurrent abortions and/or thrombosis, nine of whom had lupus anticoagulant as shown by the kaolin clotting time test. Of the 99 patients studied by all four tests, 9 showed lupus anticoagulant by both kaolin clotting time and dilute Russell's viper venom time; 7 had a history of abortion and/or thrombosis. The dilute Russell's viper venom time test is easy to perform and not affected by inhibitors to factor VIII or IX. It is recommended as a primary screening test for lupus anticoagulant detection in a hospital clinical laboratory. PMID- 1746493 TI - TestPack Strep A kit for the rapid detection of group A streptococci on 11,088 throat swabs in a clinical pathology laboratory. AB - Results obtained with Abbott Laboratories' TestPack Strep A, a rapid test kit to detect group A streptococcal antigen on throat swabs, were compared with the culture results. All tests were performed by American Society of Clinical Pathology-registered technologists in a large clinical laboratory. A total of 11,088 throat swabs were tested; 9,161 belonged to pediatric patients and 1,927 to adults. For TestPack Strep A, the study demonstrated a sensitivity value of 0.91 and a specificity value of 0.96; positive predictive value and negative predictive values were 0.82 and 0.98, respectively. These data indicate that even when performed by experienced technologists, in a laboratory setting, approximately 1 of 10 patients with group A streptococcal tonsillopharyngitis will be missed if physicians rely solely on this direct antigen test. A backup culture on all patients who are negative by a rapid antigen detection test is recommended. PMID- 1746494 TI - Rejuvenation of erythrocytes preserved with AS-1 and AS-3. AB - Rejuvenation of erythrocytes (biochemical modification of adenosine triphosphate and 2,3-diphosphoglycerate) preserved with currently available nutrient additive solutions has not been licensed or adequately studied. The ability of the commercially available solution PIPA to modify erythrocytes preserved with AS-1 or AS-3 for 35 and 42 days was studied. Use of PIPA produced greater-than-normal levels of adenosine triphosphate in the preserved erythrocytes. Restoration of 2,3-diphosphoglycerate was suboptimal at both periods. (PIPA treatment produces normal levels of 2,3-diphosphoglycerate in erythrocytes preserved for 35 days with citrate-phosphate-dextrose-adenine-1.) In erythrocytes preserved with AS-1 or AS-3 for 42 days, 2,3-diphosphoglycerate returned to normal levels after a second PIPA rejuvenation. This study demonstrates that biochemical modification is possible in erythrocytes preserved with AS-1 or AS-3 for 42 days. PMID- 1746495 TI - Laboratory hemostatic abnormalities in massively transfused patients given red blood cells and crystalloid. AB - Most of the literature on massive transfusion concerns whole blood replacement, whereas clinically, packed red blood cells are commonly given. To determine when hemostatic abnormalities occur in patients resuscitated primarily with packed red blood cells and crystalloid, the cases of 39 consecutive patients who were transfused with 10 or more red blood cell units of any kind within 24 hours were reviewed. After transfusion with 20 or more units of red blood cell products of any kind (packed red blood cells, cell-saver units, or whole blood), 75% (3 of 4) of patients had platelet counts less than 50 x 10(9)/L, compared to 0 of 29 patients given less than 20 units (P less than 0.001). After transfusion of 12 units of relatively plasma-free red blood cell products (packed red blood cells or cell-saver units), 100% (8 of 8) of patients had prothrombin time prolonged by more than 1.5 times mid-range of normal, compared to 36% (5 of 14) of patients given less than 12 units (P = 0.012). These data confirm that patients massively transfused with red blood cells of any kind develop significant thrombocytopenia after 20 units. Importantly, probably clinically significant prothrombin time and partial thromboplastin time prolongations occurred consistently after transfusion of 12 units of relatively plasma-free red blood cells in unselected patients at an urban trauma hospital. These data suggest that coagulation factor replacement is necessary in patients who receive 12 or more units of packed red blood cells or cell-saver blood, and platelet replacement is necessary in patients who receive 20 or more units of any red blood cell product. A prospective study is needed to determine whether the expected abnormal clinical bleeding indeed occurs in patients with such laboratory coagulation abnormalities and to determine when plasma transfusion is indicated in patients massively transfused with red blood cells. PMID- 1746496 TI - The mystique of the mistake. With proposed standards for validating proficiency tests in anatomic pathology. AB - Variability in classification in anatomic pathology does not necessarily indicate that a mistake has been made. It is usually an artifact, created when pathologists choose a single category from among two or more justifiable alternatives. This is most common when standard classifications with uniform terminology are not used. It also can occur when classification systems are not constructed so as to insure mutual exclusivity of categories. It is proposed that a proficiency test in anatomic pathology should not be considered scientifically valid until a professional organization primarily concerned with anatomic pathology has endorsed its proposed classification system as having categories that are close to 100% mutually exclusive in the hands of expert pathologists not involved in developing the system. All possible precautions should be taken to insure that the "right answers" for any proficiency test are generated in a way that excludes the possibility of multiple justifiable alternatives. PMID- 1746497 TI - The range of small cell tumors of the bone: yet more phenotypic variants. PMID- 1746498 TI - Multilocular cystic renal cell carcinoma. PMID- 1746499 TI - Metaplastic carcinomas and sarcomas of the breast. PMID- 1746500 TI - Underdiagnosis of alcohol dependence in psychiatric inpatients. AB - Alcoholism is prevalent among psychiatric inpatients, and accurately diagnosing alcohol problems is a critical step in treatment planning. The authors diagnosed alcohol dependence in 35 psychiatric inpatients by blind review of interview protocols and hospital records. They then examined the frequency with which admitting and attending clinicians diagnosed alcohol abuse and dependence in these patients. Alcoholism was underdiagnosed; 24% of the clinicians' diagnoses included no alcoholism diagnosis, 39% were alcohol abuse, and only 37% were alcohol dependence. Underdiagnosis was strongly associated with the presence of a comorbid psychosis, as well as with patients' denial of alcoholism and with less severe alcoholism. The authors discuss the patient and clinician variables which may contribute to underdiagnosing alcoholism and recommend educational and administrative measures to improve clinicians' diagnostic sensitivity. PMID- 1746501 TI - Substance abuse in an inpatient psychiatric sample. AB - The relationship between psychoactive drug abuse and psychopathology is complex. There have been few systematic explorations of substance abuse in psychiatric populations since the recent epidemic of cocaine abuse. To update and further explore the relationship between psychiatric illness and substance abuse, 100 consecutively admitted patients to an inpatient psychiatry unit were administered a drug and alcohol use/abuse questionnaire. Sixty-four percent endorsed current or past problems with substance abuse and 29% met DSM-III-R criteria for substance abuse in the 30 days prior to admission. For the major diagnostic categories, there were no significant differences between groups in percentages of patients with substance abuse disorders. There was a trend (p less than or equal to .2) toward an increased number of lifetime psychiatric hospitalizations in the substance-abusing group. Alcohol was the most common drug of choice followed by stimulants, cannabis, and sedative hypnotics. Differences in drug choices between diagnostic categories are discussed. Forty-three percent of urine drug screens obtained were positive, and of those with positive urine drug screens, 42% denied drug use upon admission. Only 40% of patients with current or past substance abuse problems had received treatment for their chemical dependency. In our sample, while substance abuse was very prevalent, it was underreported and undertreated. PMID- 1746502 TI - Drug abuse risk among pregnant adolescents attending public health clinics. AB - The drug abuse risk status and characteristics of pregnant adolescents (under 21 years) were evaluated at public maternal health clinics in Prince George's County, Maryland. During the project period (March 1988 to September 1989), 403 young women were interviewed. Based on those interviews, one of four risk judgments, scaled for increasing severity of risk, was assigned. Twenty percent of the sample was found to be either at high risk or current abusers of alcohol or other drugs. Risk was equally represented across both the age range (14-20 years) and marital status of the sample, but Whites were overall at significantly higher risk than Blacks (P less than .0001). Post-hoc examination of risk correlates identified drug use in the home and past or current cigarette smoking to be strongly predictive of risk (gamma = .92). While parental drug use was the most frequently reported social environment drug influence factor, as risk status of the young women increased in severity, the parental influence factor declined and the significant-other influence factor increased. A separate sample of adult women (21 years and older) was interviewed for comparison to the youth sample. PMID- 1746503 TI - Combined substance abuse and psychiatric disorders in homeless and domiciled patients. AB - Although homelessness in patients with combined addictive and psychiatric illness is a common problem, little has been reported about the epidemiology of homelessness in this patient population. The authors, in a study of 100 dually diagnosed patients admitted to a large metropolitan psychiatric hospital, found that a large portion of patients (N = 46) were homeless at the time of admission. Alcohol and crack/cocaine were the most frequently used drugs. Interestingly, there were no significant differences on most parameters between those who were homeless and those who were not. The authors observed that among the disadvantaged, inner-city dually diagnosed, many move in and out of the homeless state, seriously compromising their chances for recovery. Self-help treatment programs were more commonly used by homeless than domiciled patients. The homeless population may therefore be amenable to treatment in 12-step groups, as are domiciled patients. PMID- 1746504 TI - Effect of cocaine on thyroid functions. AB - Results of routine thyroid function tests in heavy cocaine abusers at the time of treatment admission were not statistically different from normal values for our laboratory or from a similar group of other substance abuse patients in treatment. This suggests that heavy cocaine use per se does not affect thyroid function. Therefore, if the thyroid function tests are abnormal in a cocaine abuser, then a true thyroid dysfunction should be considered and completely evaluated. In addition, nonspecific alterations in thyroid function tests in nonthyroidal illnesses should be kept in mind. PMID- 1746505 TI - The intoxication power of alcoholic beverages: image and reality. AB - Because of the newness of wine coolers and their youthful appeal, questions have arisen of whether consumers have a realistic understanding of coolers' intoxication power. Questionnaires were given to 459 undergraduates to determine how accurately they could estimate the number of drinks (beer, light beer, wine, wine coolers, and whiskey) they would have to consume to become legally intoxicated. Results indicate that, although responses differ by race and gender, respondents have a poor understanding of the intoxication power of alcohol in general and of hard liquor and wine coolers in particular. Whereas liquor's intoxication power was overestimated, the intoxication power of wine coolers was underestimated relative to other types of drinks by the total sample and underestimated in absolute terms by females. PMID- 1746506 TI - Risk factors associated with alcohol abuse in college students. AB - A survey of 989 college students was conducted to investigate risk factors- gender, family history of alcohol abuse, family history of depression and mental illness, childhood hyperactivity, and antisocial personality-associated with alcohol abuse. Two hundred ninety-four subjects (29%) completing the alcohol subscale of the Diagnostic Interview Schedule met lifetime DSM-III criteria for alcohol abuse. Utilizing a loglinear model, expression of childhood and early adolescent deviant behavior, family history of depression, and gender were shown to be significantly associated with alcohol abuse among students. PMID- 1746507 TI - Buprenorphine for pain relief in a patient with drug abuse. AB - Buprenorphine is a mixed opioid agonist/antagonist which appears to produce less physical dependence and respiratory depression than typical mu-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a mu-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia. PMID- 1746508 TI - Improving the people's health: some Hopkins' contributions. PMID- 1746509 TI - The Washington County Training Center: an exemplar of public health research in the field. PMID- 1746510 TI - Adapting to specialization: the founding, growth, and transformation of the American Journal of Hygiene. PMID- 1746511 TI - American Journal of Epidemiology: its evolution since 1965. PMID- 1746512 TI - Seventy years ago in the Journal. PMID- 1746513 TI - Epidemiology is the study of "epidemics" and their prevention. PMID- 1746514 TI - Epidemiology and public policy. PMID- 1746515 TI - Statistical reasoning in epidemiology. PMID- 1746516 TI - Case investigation in epidemiology. PMID- 1746517 TI - The interaction of basic science and population-based research: autoimmune thyroiditis as a case history. AB - This brief commentary illustrates how laboratory research compliments populational research. The finding that susceptibility to autoimmune thyroid disease in animals is due to the additive effects of a number of unrelated genes led to a field study of a genetically predisposed population. In humans, as in animals, the major histocompatibility complex plays a preeminent role. Unlike many other autoimmune diseases, however, different HLA haplotypes predominate in different families, just as different H-2 haplotypes determine susceptibility in different strains of mice. Like the predisposed chicken, humans have a number of other genes that act independently to influence autoimmune susceptibility. Insight into the nature and action of the additional genes depends upon renewed studies of the animal models. Thus, we see a symbiotic relation between basic science as practiced in the laboratory and population-based research in the field. PMID- 1746518 TI - "Race" in the epidemiologic literature: an examination of the American Journal of Epidemiology, 1921-1990. AB - The routine presentation of epidemiologic data by "race" has been challenged as impeding identification of modifiable risk factors and fostering an unsubstantiated belief in the biologic distinctness of the "races." This study examines the past and current uses of "race" in US epidemiologic research. The authors reviewed every paper published in the 1921, 1930, 1940, 1950, and 1960 volumes of the American Journal of Hygiene and in the 1965, 1970, 1975, 1980, 1985, and 1990 volumes of the American Journal of Epidemiology. Of the total of 1,200 papers published during the sample years, 558 reports of original epidemiologic research conducted in the United States were identified. The proportion of these papers containing a reference to "race" rose steadily from 1975. However, the proportion of papers reporting inclusion of "nonwhite" populations did not show a parallel increase. Exclusion of "nonwhite" subjects and description of predominantly "white" study populations increased instead. Recommendations for future epidemiologic practice include the following: 1) greater inclusion of "nonwhite" populations in epidemiologic research and 2) vigorous investigation of the root causes of observed "race"-associated differences. PMID- 1746519 TI - Migration, blood pressure pattern, and hypertension: the Yi Migrant Study. AB - Rural-urban migration provides an ideal opportunity to examine the effects of environment and genes on blood pressure. The effect of migration on the Yi people of China was studied. The Yi people live in a remote mountain area in southwestern China. In 1989, blood pressure was measured in 14,505 persons (8,241 Yi farmers, 2,575 urban Yi migrants, and 3,689 Han urban residents) aged 15-89 years. Different patterns were seen for men and women. Among the men, Yi farmers had the lowest mean blood pressure, the least rise in blood pressure with age (systolic blood pressure, 0.13 mmHg/year; diastolic blood pressure, 0.23 mmHg/year), and the lowest prevalence of hypertension (0.66%). In contrast, both Yi migrant men and Han men had higher levels of mean blood pressure, rise in blood pressure with age (Yi migrants: systolic pressure, 0.33 mmHg/year; diastolic pressure, 0.33 mmHg/year; Han: systolic pressure, 0.36 mmHg/year; diastolic pressure, 0.23 mmHg/year), and prevalence of hypertension (Yi migrants, 4.25%; Han, 4.91%). Among the women, however, mean systolic pressure was higher in Yi farmers than in Yi migrants or in Han. Diastolic pressure was similar among the three groups. However, the Yi farmer women's age-related rise in blood pressure (systolic pressure, 0.06 mmHg/year; diastolic pressure, 0.14 mmHg/year) and their prevalence of hypertension (0.33%) were lower than those in the other two groups. Yi migrant women had an intermediate rise in blood pressure with age (systolic pressure, 0.37 mmHg/year; diastolic pressure, 0.23 mmHg/year) and prevalence of hypertension (2.40%). Han women had the greatest rise in blood pressure with age (systolic pressure, 0.56 mmHg/year; diastolic pressure, 0.36 mmHg/year) and the highest prevalence of hypertension (4.76%). For both men and women, the above differences were only partially explained by age, body mass index, heart rate, smoking, and alcohol use. This study, using standardized methods, demonstrates an important effect of migration on rise in blood pressure with age and on the prevalence of hypertension. PMID- 1746520 TI - A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. AB - The Baltimore Eye Survey was a population-based survey conducted from January 1985 to November 1988 among residents of east Baltimore, Maryland, who were 40 years of age or older. A total of 5,308 black subjects and white subjects received a comprehensive screening examination for glaucoma including tonometry, visual fields, stereoscopic fundus photography, and a detailed medical and ophthalmic history. Based on a definitive examination, a diagnosis of glaucoma of any type was made for 196 persons. Tonometry, cup:disc ratio, and narrowest neuroretinal rim width were evaluated for their ability to correctly classify subjects into diseased or nondiseased states. There were no cutoff values at which these variables provided a reasonable balance of sensitivity and specificity, separately or in combination. Logistic regression models were fit that included demographic and other risk factors. Sensitivities and specificities were calculated for varying cutoff levels on the distribution of predicted probabilities. There was no cutoff for which reasonable sensitivity and specificity were obtained. The authors conclude that the effectiveness of current techniques for glaucoma screening is limited. PMID- 1746521 TI - Age- and sex-specific incidence rates of migraine with and without visual aura. AB - Age- and sex-specific incidence rates for the onset of migraine headache with and without preceding visual aura were estimated from a population-based telephone interview survey conducted between March 1986 and June 1987 of 10,169 randomly selected residents of Washington County, Maryland, between the ages of 12 and 29 years. A total of 392 males and 1,018 females were identified as having a history of migraine. Of these, 27% of male cases and 28% of female cases were defined as having migraine with visual aura. Among both males and females, the incidence rate for migraine with visual aura appears to have peaked as much as 3-5 years earlier than the age peak for migraine without aura. For males, the age-specific incidence for migraine with visual aura appears to have peaked on or before 5 years of age at 6.6/1,000 person-years, or possibly higher. In contrast, the highest incidence for migraine without aura occurred between 10 and 11 years of age at 10.1/1,000 person-years. New cases of migraine were uncommon among males in their late 20s. The initial onset of migraine headache begins at a later age among females than among males. For females, the highest incidence of migraine with aura occurred between 12 and 13 years of age at 14.1/1,000 person-years; the highest incidence for migraine without aura occurred between 14 and 17 years of age at 18.9/1,000 person-years. In contrast to males, new onset of migraine was relatively common among females in their late 20s. PMID- 1746522 TI - Factors associated with osteoarthritis of the hand in males: data from the Baltimore Longitudinal Study of Aging. AB - The association of metabolic and physiologic factors with hand osteoarthritis was studied in 888 Caucasian male subjects aged 17-102 years in the Baltimore Longitudinal Study of Aging. Left-hand radiographs taken between 1958 and 1975 were read by one investigator for grade of osteoarthritis using Kellgren-Lawrence scales. Possible risk factors, assessed at the same visit as the last radiograph during this interval, included age and measures of bone mass, body composition, muscle mass, and muscle strength. Results of bivariate analyses of these cross sectional data showed that increasing grade of hand osteoarthritis was associated with increasing age; greater mean levels of waist/hip ratio and percentage of body fat; and lower mean levels of percentage of cortical area, grip strength, and forearm circumference. After adjustment for age using residuals from best-fit quadratic regression models, none of these independent variables remained significantly associated with grade of hand osteoarthritis. These data fail to support hypotheses that metabolic and physiologic factors are associated with hand osteoarthritis independent of their known age-related changes. PMID- 1746523 TI - Hip fractures among the elderly: factors associated with in-hospital mortality. AB - Factors associated with mortality were examined for 27,370 hip fracture patients aged 65 years or older in Maryland hospitals, using discharge data for 1979-1988. Variables of interest included sociodemography, principal medical and injury diagnoses, E-code, year, disposition, and hospital. For both white males and white females, the hip fracture rate doubled with each 5-year increment in age. The overall proportion who died during hospitalization was 4.9% (n = 1,339). After multivariate adjustment, there remained a substantially increased risk of death for males. The relative odds (RO) of dying for males versus females were 1.6. Other factors associated with high relative odds of dying during hospitalization included the diagnosis of septicemia (RO = 12.3), pneumonia/influenza (RO = 4.9), and digestive system disorder (RO = 3.6). The RO of dying doubled in the presence of cardiac, neoplastic, or cerebrovascular disease. Patients with diagnoses of nervous system or mental disorder, hypertension, anemia, musculoskeletal system disease, or urinary tract infection were at decreased risk of dying. Results of the study suggest that the prevention or early diagnosis and treatment of serious infections in the elderly patient with a hip fracture remain an important challenge to clinicians. PMID- 1746524 TI - The driver's role in fatal two-car crashes: a paired "case-control" study. AB - This population-based study examines drivers' characteristics associated with driving errors that resulted in fatal motor vehicle crashes. Routinely collected data from the Fatal Accident Reporting System were used to assess whether a driver initiated the crash (case) or was passively involved (control) in 6,506 two-car collisions (81% of 7,993 eligible events). A paired comparison of cases and controls avoided confounding by environmental factors, exposure to traffic, and differences in case fatality. The strongest predictor of crash initiation is alcohol (odds ratio (OR) = 11.5; 95% confidence interval (CI) 9.57-13.9). Odds ratios are elevated even at the lowest blood alcohol concentration levels and increase dramatically as alcohol levels rise. Drivers aged 40-49 years are least likely to initiate crashes; odds ratios rise in a U-shaped manner to 3.35 in teenagers (95% CI 2.72-4.13) and to 22.1 in drivers over 80 years (95% CI 14.2 34.5). Other risk factors for initiating a fatal crash are the following: not wearing a seat belt (OR = 1.54; 95% CI 1.35-1.75), driving without a valid driver's license (OR = 2.16; 95% CI 1.72-2.73), and having had a crash within the last year (OR = 1.21; 95% CI 1.07-1.38). Driving errors leading to fatal crashes do not occur at random, but are associated with specific driver characteristics. The risk factors for crash initiation among crash-involved drivers are similar to risk factors for crash involvement found in other studies. These findings suggest that driving errors often explain high rates of crash involvement, invite further use of crash initiation in traffic injury research, and underscore the value of population-based registries for analytic epidemiology. PMID- 1746525 TI - Methodological issues in using hospital discharge data to determine the incidence of hospitalized injuries. AB - Estimates of the incidence of hospitalized injuries based on hospital discharge data are inconsistent because of variations in 1) the definition of injury and 2) the criteria for excluding repeat admissions for the same injury event. Using 1983 data from the Uniform Hospital Discharge Data Set for the state of Rhode Island, the authors demonstrate the effects on injury incidence rates associated with the various definitions and exclusion criteria used in previous studies. The overall injury rate (11.9/1,000 population) was substantially reduced (rate difference, 1.7; 95% confidence interval 1.2-2.1) when adverse effects or complications of medical and surgical care ("medical injuries"), not usually defined as injuries by injury researchers, were excluded. Estimates of the incidence of "true" injury hospitalizations (excluding medical injuries, late effects, and complications of care) ranged from 9.9/1,000, when repeat admissions identified as transfers from another acute facility were excluded, to 7.2/1,000, when repeat admissions identified as elective admissions were excluded. Marked variability in incidence rate estimates by age, sex, nature of injury, and state of residence of victim was also noted. The addition to hospital discharge data sets of a separate variable to identify readmissions for the same problem would result in more valid incidence estimates for injury research and surveillance. PMID- 1746526 TI - Interpartner reliability of reporting of recent sexual behaviors. AB - Epidemiologic studies exploring risks for sexually transmitted diseases, including human immunodeficiency virus infection, typically rely on self-report of sexual behaviors. Estimates of the incidence and prevalence of sexual practices are important measures for assessment of behavioral interventions as well as for examining disease transmission. This study examined the degree of agreement within heterosexual couples reporting frequency and type of sexual behaviors, including condom use. Self-reports were obtained from 71 couples attending Baltimore sexually transmitted disease clinics in 1989-1990 regarding the number of days and number of episodes of three specific sexual practices (any type of sexual activity, vaginal sex, and vaginal sex with condom use) over a 30 day period. Paired t test analysis revealed both sexes to be very consistent in their reporting of recent sexual experiences. Multivariate analysis showed that agreement did not vary by socioeconomic status, by whether the partners were married to each other, or by age. These findings suggest that reliable information regarding sexual behaviors may be obtained from men or women. PMID- 1746527 TI - Race, family income, and low birth weight. AB - The relations among race, family income, and low birth weight were examined using information obtained from the National Longitudinal Survey of Youth, which conducted yearly interviews with a nationally representative sample of young women identified in the late 1970s. Data were available for these women and their offspring from 1979 through 1988. Maternal education, maternal age, age/parity risk, marital status, and smoking during pregnancy served as covariates in cross sectional and longitudinal analyses. The risk of low birth weight among births to black women and white women who were poor was at similarly high levels regardless of whether poverty was determined prior to study entrance or during the study period. Longitudinal analyses showed an exceptionally large increase in risk of low birth weight among children born to women whose prior pregnancy ended in a low-birth-weight infant. These two findings emphasize the importance of factors antecedent to the pregnancy in the genesis of low birth weight. PMID- 1746528 TI - New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1. AB - To examine whether recent intravenous use of cocaine might be associated with increased risk of human immunodeficiency virus type 1 (HIV) infection, the authors studied 2,597 active intravenous drug users: 2,399 with recent cocaine injection and 198 with recent injection of heroin or other drugs but not cocaine. These subjects were adult residents of Baltimore City and the surrounding Maryland counties, recruited via outreach into the community between February 1988 and March 1989. In contrast to the first report on the cocaine-HIV association, the present study sample was not recruited solely from drug treatment programs. In the present study, estimated HIV seroprevalence was 26.4% for recent cocaine injectors as compared with 10.6% among all other recent intravenous drug users; the relative odds estimate was 3.03. In the untreated segment of the sample, HIV seroprevalence was 26.0% for recent cocaine injectors as compared with 8.9% among others (relative odds (RO) = 3.61). The estimated degree of association did not change appreciably when multiple logistic regression was used to hold constant potentially confounding and/or mediating variables such as receptive anal intercourse, number of sex partners, and use of injection equipment obtained at shooting galleries (RO = 2.64). Augmenting these cross-sectional data, preliminary prospective data showed excess risk of HIV seroconversion among recent cocaine injectors (estimated relative risk = 2.11). While other research has examined the cocaine-HIV association, the present study differs in that it has allowed a test for whether the association was a spurious artifact of studying drug users recruited solely from drug treatment programs, a broad array of alternative determinants of HIV infection have been held constant, and the association has been examined with seroconversion data. The results lend support to the abiding concern about the risk of HIV infection among cocaine users. PMID- 1746529 TI - Estimating the 1978-1990 and future spread of human immunodeficiency virus type 1 in subgroups of homosexual men. AB - The authors studied the historical spread of human immunodeficiency virus type 1 (HIV-1) infection in homosexual/bisexual men and projected its future spread in these men using data from an AIDS-free cohort recruited during late 1984 in Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Dates of preentry seroconversion in HIV-1 seroprevalent men were estimated using study entry values of hematologic variables influenced by HIV-1 infection. The authors used survival methods incorporating truncation to determine numbers/dates of seroconversion for men with a pre-1984 AIDS diagnosis who were selectively excluded by design from the 1984 AIDS-free cohort. Overall, the annual seroconversion hazard rose progressively from 0.4% in 1978 to 13.8% in 1983, dropped to 4.6% in 1985, and remained relatively stable at 1.1-2.2% from 1986 to 1990. By January 1990, almost 46% of men who were seronegative in 1978 had seroconverted. The authors estimated historical rates of spread by city, age, education, and ethnicity to examine the effects of these factors in the early and continuing stages of the HIV-1 epidemic. There were striking differences among cities with respect to pre-1985 seroconversion rates but not with respect to post 1985 seroconversion rates. Age, education, and ethnicity were all associated with 1978-1990 seroconversion rates. Future seroconversion among homosexual men was predicted assuming that the "stabilized" 1986-1990 hazards (stratified by age) observed here will be representative of future rates. Truncated Kaplan-Meier methods gave the probability of a seronegative 20-year-old man's remaining seronegative in subsequent years. Such a man has a 20.2% chance of seroconverting before reaching the age of 25 years (a 4.4% yearly hazard). The annual hazard drops to 2.5% between 25 and 30 years, to about 1.5% between 30 and 45 years, and to 1.0% between 45 and 55 years. The overall probability of seroconversion prior to age 55 years is about 50%, with seroconversion still continuing at and after age 55. Given that this cohort consists of volunteers receiving extensive anti HIV-1 transmission education, the future seroconversion rates of the general homosexual population may be even higher than those observed here. PMID- 1746530 TI - Effects of age, breast feeding, and household structure on Haemophilus influenzae type b disease risk and antibody acquisition in Alaskan Eskimos. AB - Invasive Haemophilus influenzae type b (Hib) disease occurs with unusually high incidence in Alaskan Eskimos. In 1983, the authors evaluated the unique susceptibility of the Yupik-speaking Eskimo population in southwest Alaska. A matched case-control design was used to assess the influence of age, breast feeding, and household composition on disease risk, with a historical cohort design to evaluate their effects on acquisition of Hib anticapsular antibody. The authors studied 103 cases with known invasive Hib disease that occurred at a mean age of 8.7 +/- 8.6 months; healthy controls were matched for age and village of residence. Living in extended families at the time of disease onset was significantly associated with Hib disease (p less than 0.04; odds ratio = 1.8; 95% confidence interval 0.87-3.25). The authors found that breast feeding was significantly less common among cases than controls (p less than 0.03; odds ratio = 0.53; 95% confidence interval 0.27-0.98). Although there was a positive correlation between age and acquired level of total anticapsular antibody (r = 0.59; p less than 0.0001), previous exposure to invasive Hib disease did not influence these levels. Household crowding and breast feeding also did not appear to affect Hib antibody acquisition. PMID- 1746531 TI - Applicability of industrial sampling techniques to epidemiologic investigations: examination of an underutilized resource. AB - In carrying out surveys to estimate disease prevalence or health services coverage in a region, investigators are often interested in identifying communities or other subareas in which the problem of interest is especially severe. In view of the large number of subareas to be examined, the investigator seeks rapid methods of assessment that require minimum sampling in each. Lot quality assurance sampling, developed more than 60 years ago to meet industrial quality control needs, has been found to serve public health purposes as well. Curiously, other more recent and more powerful industrial techniques have not received the recognition they deserve. Several of them are discussed in this paper and likely applications are cited. They fall into two categories: 1) lot acceptance methods to depict static conditions in a population and 2) more dynamic process monitoring methods for continuous surveillance. Under the first category, techniques of double sampling and sequential sampling are described. Reduced and tightened scrutiny, control charts, and exponential smoothing are highlighted as especially promising approaches under the process control category. PMID- 1746532 TI - Differential misclassification arising from nondifferential errors in exposure measurement. AB - Misclassification into exposure categories formed from a continuous variable arises from measurement error in the continuous variable. Examples and mathematical results are presented to show that if the measurement error is nondifferential (independent of disease status), the resulting misclassification will often be differential, even in cohort studies. The degree and direction of differential misclassification vary with the exposure distribution, the category definitions, the measurement error distribution, and the exposure-disease relation. Failure to recognize the likelihood of differential misclassification may lead to incorrect conclusions about the effects of measurement error on estimates of relative risk when categories are formed from continuous variables, such as dietary intake. Simulations were used to examine some effects of nondifferential measurement error. Under the conditions used, nondifferential measurement error reduced relative risk estimates, but not to the degree predicted by the assumption of nondifferential misclassification. When relative risk estimates were corrected using methods appropriate for nondifferential misclassification, the "corrected" relative risks were almost always higher than the true relative risks, sometimes considerably higher. The greater the measurement error, the more inaccurate was the correction. The effects of exposure measurement errors need more critical evaluation. PMID- 1746533 TI - Intravenous immunoglobulin in the treatment of human immunodeficiency virus related thrombocytopenia. AB - Fourteen patients with sexually transmitted human immunodeficiency virus (HIV) related immune thrombocytopenia were treated with intravenous gammaglobulin (IVIG). The patients were treated with a uniform program consisting of 1 g/kg of IVIG on day 1 and day 2, followed by 1 g/kg on day 15. Most patients had pretreatment bleeding symptoms, which included petechiae, spontaneous and traumatic ecchymoses, gum bleeding, and epistaxis. Median baseline platelet count was 17,000/mm3 (range 3-61,000/mm3). After the infusion of the IGIV, all patients had a resolution of their bleeding by day 8. The median maximum platelet count achieved with the IGIV was 220,000/mm3 (range 76-426,000/mm3). No patient achieved either a sustained complete or partial remission after the conclusion of the IVIG therapy. Toxicities were minimal with the majority being headache and nausea. In conclusion, patients with sexually transmitted HIV infection and immune thrombocytopenia respond favorably to IVIG. This treatment should be considered as first-line therapy for patients with HIV-related immune thrombocytopenia who require immediate but temporary increase in their platelet count, attributable to symptoms or signs of clinical bleeding or because of the need for an invasive procedure. PMID- 1746534 TI - Epirubicin and cytosine arabinoside for the induction therapy of childhood acute nonlymphocytic leukemia. AB - Epirubicin, a new anthracycline, was used in combination with cytosine arabinoside for the induction therapy of de novo acute nonlymphocytic leukemia in childhood. The treatment consisted of epirubicin 20 mg/m2/day for 3 days and cytosine arabinoside 100 mg/m2/day for 7 days. The treatment could be repeated every 3 weeks. Remission induction rate was 80% (20/25). Moreover, in 13 patients, the remissions were obtained after a single course. In general, the side effects of epirubicin and cytosine arabinoside were tolerable. However, the main causes of all the three deaths were infections. Our study suggests that epirubicin is acceptable and effective for the induction therapy for de novo acute nonlymphocytic leukemia in childhood. PMID- 1746535 TI - Lupus anticoagulant associated with primary malignant lymphoplasmacytic lymphoma of the spleen: a report of four patients. AB - Primary lymphoma of the spleen is characterized by predominant splenomegaly. Lymphoplasmacytic malignant lymphoma of the spleen, of low malignancy in the Kiel classification, low and intermediate grade in the National Cancer Institute Working Formulation (NCIWF), is rare. It is often associated with a monoclonal immunoglobulin M (IgM). Four patients presenting with primary splenic lymphoma of plasmacytic type associated with a high level of monoclonal IgM and a lupus anticoagulant (LA) are described. This association has not previously been reported. In contrast with the usual heterogeneity of LA, this LA is relatively homogeneous with an important prolongation of the prothrombin time (greater than 18 sec for a control of 12), more prolonged partial thromboplastin time (PTT) of the mixture patient + control plasma than PTT of the patient plasma. Despite the important coagulation abnormalities, none of these four patients has presented any hemorrhagic or thrombotic complications, even during major surgery such as splenectomy. The lupus-like anticoagulant effect ran parallel with the monoclonal IgM. Survival, after splenectomy and chemotherapy, appears to be favourable: three patients are alive with survivals of greater than or equal to 7 years. The follow-up is as yet too short for the last patient. PMID- 1746536 TI - Hemoglobin constant spring in Bangkok: molecular screening by selective enzymatic amplification of the alpha 2-globin gene. AB - Hemoglobin Constant Spring (Hb CS) is a hemoglobin variant with an elongated alpha-globin chain secondary to a chain termination mutation. The diagnosis of HbCS by electrophoresis is difficult because it is present in very low amounts in the red cells of heterozygotes. Selective enzymatic amplification of the alpha 2 globin gene and allele-specific hybridization for Hb CS gene provided accurate diagnosis of Hb Constant Spring. We have used this approach to detect the alpha cs mutation in the cord blood that contained all four alpha-globin genes but had Hb Bart on electrophoresis. The alpha cs mutation was found in six subjects whose Hb Bart levels were 3.0, 3.2, 3.7, 4.0, 4.9, and 9.8%. The latter also had -alpha mutation on the other chromosome, giving rise to the genotype alpha cs alpha/ alpha, which produced high Hb Bart. The gene frequency for alpha cs in the Thai calculated from a total of 406 cord blood studied in Bangkok was found to be approximately 0.008. PMID- 1746537 TI - An effective acute graft-vs.-host disease prophylaxis with minidose methotrexate, cyclosporine, and single-dose methylprednisolone. AB - Cyclosporine and methotrexate at standard doses (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of acute graft-vs.-host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single-dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2 (5 mg/m2 on days 1, 3, and 6, and then 10 mg/m2 on days 11 and 18) and then to 20 mg/m2 (5 mg/m2 on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose. PMID- 1746538 TI - Characterization of novel platelet and endothelial cell target antigens in a family with genetic susceptibility to autoimmunity. AB - This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia. PMID- 1746539 TI - The single zeta globin gene rearrangement: hematologic phenotype and its frequent occurrence in Polynesian Niueans. AB - The single zeta globin gene rearrangement (-zeta/) is an unusual mutation associated with the alpha globin gene cluster on chromosome 16p13.3. It has been detected regularly among West Africans (gene frequency approximately 0.05) and sporadically among other populations. DNA samples from 186 Polynesian Niueans living in Auckland, New Zealand, were studied. Eighteen (gene frequency 0.05) were shown to have the -zeta/gene arrangement, which results from loss of the psi zeta 1 gene. Hematological phenotypes in six cord blood samples and 12 affected adults were normal. The high frequency for -zeta/in Niueans may represent another example of genetic drift and a founder effect in Polynesians or may reflect a different founding population. PMID- 1746540 TI - Simple method for differentiating between HLA and platelet-specific antibodies by flow cytometry. AB - Since platelets express both platelet-specific and class I HLA antigens, serum antiplatelet reactivity assessed by most platelet antibody techniques could be due to antibodies with either or both specificities. Flow cytometric analysis of sera for detection of antiplatelet antibody commonly employs a purified platelet preparation as target cells. A method is described for investigating sera for platelet antibodies by flow cytometry using a mixture of platelets and lymphocytes. The mixture of lymphocytes and platelets as target cells has the advantage of confirming the presence of the HLA antibodies in reactive sera. The concomitant use of platelets and lymphocytes treated with citric acid, pH3, or with chloroquine (to remove or alter surface HLA antigens without affecting platelet specific antigens) may further assist in identifying antiplatelet antibodies in alloimmunized patients. These techniques may also be useful in platelet crossmatching procedures. PMID- 1746541 TI - Hemophagocytic syndrome associated with aggressive natural killer cell leukemia. AB - We describe a patient who had aggressive natural killer cell leukemia with profound hemophagocytosis. This combination must be underscored as one of several hemophagocytic syndromes. Activated phagocytes in the bone marrow appeared morphologically normal and could possibly be proliferating in response to some cytokine(s) such as interferon-gamma produced by leukemic cells, whose serum level was found to be extremely elevated in this case. PMID- 1746542 TI - Disseminated toxoplasmosis in a severely immunodeficient patient: demonstration of cysts in bone marrow smears. AB - A 30-year-old woman was treated with unrelated HLA-compatible bone marrow transplantation for acute myeloid leukemia. Examination of her bone marrow smears because of fever and pancytopenia revealed the presence of Toxoplasma cysts. Although Toxoplasma cysts are rarely found in the bone marrow, bone marrow examination in the immunocompromised patient offers rapid diagnosis of systemic toxoplasmosis. PMID- 1746543 TI - Immunologic thrombocytopenia followed by thrombotic thrombocytopenic purpura in two HIV1 patients. AB - Two homosexual HIV1-positive male patients with thrombotic thrombopenic purpura (TTP) were found to have past history of immune thrombocytopenia (ITP). The first patient had ITP 10 months prior to TTP and was successfully treated by splenectomy. The second patient had ITP 32 months before TTP. No specific treatment was given for his asymptomatic ITP. Association of HIV infection to TTP seems to be frequent. These two types of purpura have different pathogenic mechanisms but share a common altered immune response to antigenic challenge. The occurrence of ITP and TTP in HIV-positive patients may lead to errors in diagnosis and therapy. PMID- 1746544 TI - Aplastic anemia associated with systemic lupus erythematosus. AB - Hematologic complications of systemic lupus erythematosus (SLE) usually involve peripheral destruction of blood cells. We report a case of aplastic anemia associated with SLE observed during the remission phase of SLE 3 months after the beginning of treatment. CD8+ T cells in the patient's bone marrow may have suppressed maturation of hematopoietic progenitor cells, which may have induced the aplastic anemia associated with SLE. Repeated therapy with high-dose methylprednisolone resulted in lasting remission. PMID- 1746545 TI - Vitamin E treatment in triplicated alpha-globin gene-heterozygous beta thalassemia. PMID- 1746546 TI - Hemostasis in malignancy. PMID- 1746547 TI - Dengue virus infection-associated hemophagocytic syndrome. PMID- 1746548 TI - Dissecting the genetic contribution to coronary heart disease. PMID- 1746549 TI - Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol. AB - A large segment of the population is modifying its dietary cholesterol intake to achieve a healthier life-style. However, all individuals do not respond equally. We have investigated the effects that that two physiologically important polymorphisms in the apolipoprotein (apo) E and B genes have on the responses of plasma lipid, lipoprotein, and apolipoprotein levels to a high-cholesterol diet. Over a 6-wk period, individuals were prescribed two diets, one consisting of 300 mg dietary cholesterol/d for 3 wk and one consisting of 1,700 mg dietary cholesterol/d for 3 wk. Total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and apo B levels were significantly increased on the high-cholesterol diet. Average total cholesterol (numbers in parentheses are SDs) went from 167.6 (23.4) mg/dl on the low-cholesterol diet to 190.8 (36.2) mg/dl on the high cholesterol diet; LDL-C went from 99.9 (24.8) mg/dl to 119.2 (33.4) mg/dl, and apo B went from 74.9 (24.5) mg/dl to 86.8 (29.5) mg/dl. In 71 individuals, the frequencies of the apo epsilon 2, epsilon 3, and epsilon 4 alleles were .09, .84, and .07, respectively. The frequency of the longer, apo B signal peptide allele (5'beta SP27) was .68. Apo epsilon 2/3 individuals had significantly lower LDL-C levels than did epsilon 3/3 homozygotes, on both the low-cholesterol diet (LDL-C lower by 21 mg/dl) and the high-cholesterol diet (LDL-C lower by 27 mg/dl). Average triglyceride levels were significantly different among apo B signal peptide genotypes, with the 5'beta SP27/37 homozygotes having the lowest levels (70 mg/dl). When individuals were switched from the low-cholesterol diet to the high-cholesterol diet, in no case were the average responses in lipid levels significantly different among apo E or B genotypes. Therefore, these gene loci do not have a major effect on the response of lipid levels to increased dietary cholesterol. PMID- 1746550 TI - Genetic studies of human apolipoproteins. XX. Genetic polymorphism of apolipoprotein J and its impact on quantitative lipid traits in normolipidemic subjects. AB - Apolipoprotein J (apo J) is a newly identified member of a growing family of proteins associated with various lipoprotein particles. Apo J is a glycoprotein which exists in the plasma associated with high-density lipoprotein subfractions which also contain apo A-I and cholesteryl ester transfer protein (CETP). We have investigated the possible existence of genetic polymorphism at the apo J structural locus and have evaluated its role in lipid metabolism. By employing isoelectric focusing and immunoblotting techniques, we have screened plasma or serum samples from six population groups: U.S. whites, Amerindians, Eskimos, New Guineans, U.S. blacks, and Nigerian blacks. Apo J revealed a common two-allele polymorphism only in populations with African ancestry and was found to be monomorphic in all other population groups tested. The genetic basis of the two alleles designated--APO J*1 and APO J*2, at a single structural locus, apo J-- was confirmed in a large number of segregating families. In the U.S. blacks, the frequencies of the APO J*1 and APO J*2 alleles were .76 and .24, respectively, and in the Nigerian blacks these values were .72 and .28, respectively. In addition, a single example of a rare allele designated APO J*3 was also encountered in the U.S. black sample. In Nigerian blacks, the apo J polymorphism's impact on seven quantitative lipid traits--total cholesterol, LDL cholesterol, HDL-cholesterol, HDL3-cholesterol, HDL2-cholesterol, VLDL cholesterol, and triglycerides--was investigated. No significant impact of the apo J polymorphism was observed for any of these lipid traits. PMID- 1746551 TI - Statistical methods for multipoint radiation hybrid mapping. AB - On the basis of the earlier work of Goss and Harris, Cox et al. introduced radiation hybrid (RH) mapping, a somatic cell genetic technique for constructing fine-structure maps of human chromosomes. Radiation hybrid mapping uses X-ray breakage of chromosomes to order a set of genetic loci and to estimate distances between them. To analyze RH mapping data Cox et al. derived statistical methods that employ information on sets of two and four loci, to build an overall locus order. Here we describe alternative nonparametric and maximum-likelihood methods for the analysis of RHs that use information on many loci simultaneously, including information on partially typed hybrids. Combination of these multipoint methods provides a statistically more efficient solution to the locus-ordering problem. We illustrate our approach by applying it to RH mapping data on 14 markers in 99 radiation hybrids for the proximal long arm of human chromosome 21. PMID- 1746552 TI - Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). AB - We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies. PMID- 1746553 TI - Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4. AB - Wolf-Hirschhorn syndrome is a clinically recognizable, multiple congenital anomaly syndrome usually associated with terminal deletion of the short arm of chromosome 4. A girl with clinical features of Wolf-Hirschhorn syndrome did not show an obvious deletion of chromosome 4, and a molecular defect was suspected. RFLPs of genomic DNA from the proband and her parents were studied using DNA probes from the distal region of chromosome 4p. Fluorescence in situ hybridization using a cosmid p847.351 containing the fragment 847 E-C was performed to investigate the possibility of a subtle translocation. Cytogenetic analyses done on the child and on both parents did not conclusively reveal abnormalities of chromosome 4. Molecular studies using two probes mapped to distal 4p showed the absence of the maternal haplotype in the child. These findings are thus consistent with a molecular deletion of 4p and confirm the diagnosis of Wolf-Hirschhorn syndrome. Cytogenetic experiments involving fluorescence in situ hybridization showed that the mother carried a subtle translocation between chromosomes 4 and 19, 46,XX,t(4,19)(p16.3; p13.3), which resulted in an unbalanced form in the child. Chorionic villus sampling for prenatal diagnosis in a subsequent pregnancy showed the fetus to be unaffected. This provides the first evidence, in chromosome 4p, of a molecular deletion due to a subtle, inherited translocation leading to the Wolf-Hirschhorn phenotype. Such subtle translocations may become an important mechanism for some recurrent genetic defects. PMID- 1746554 TI - The genetic and environmental sources of body mass index variability: the Muscatine Ponderosity Family Study. AB - The role of genetic and environmental factors in determining the variability in body mass index (BMI; kg/m2) was investigated in 1,302 relatives identified through 284 schoolchildren from Muscatine, IA. BMI levels were first adjusted for variability in age, by gender and by relative type. There was significant familial aggregation of adjusted BMI in the pedigrees, as indicated by inter- and intraclass correlation coefficients significantly different from zero. A mixture of two normal distributions fit the adjusted BMI data better than did a single normal distribution. Genetic and environmental models that could explain both the familial aggregation and the mixture of normal distributions were investigated using complex segregation analysis. There was strong support for a single recessive locus with a major effect that accounted for almost 35% of the adjusted variation in BMI. Polygenic loci accounted for an additional 42% of the variation. Approximately 23% of the adjusted variation was not explained by genetic factors. For spouses living in the same household, their shared environment accounted for 12% of their variation. For siblings living in the same household, their shared environment accounted for 10% of their variation. While shared environments contributed to variation in adjusted BMI, more than 75% of the variation was explained by genetic factors that include a single recessive locus. Approximately 6% of the individuals in the population from which these pedigrees were sampled are predicted to have two copies of the recessive gene, while 37% of the individuals are predicted to have one copy of the gene. PMID- 1746555 TI - Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium. AB - Linkage of at least two complementation groups of ataxia-telangiectasia (AT) to the chromosomal region 11q23 is now well established. We provide here an 18-point map of the surrounding genomic region, derived from linkage analysis of 40 CEPH families. On the basis of this map, 111 AT families from Turkey, Israel, England, Italy, and the United States were analyzed, localizing the AT gene(s) to an 8-cM sex-averaged interval between the markers STMY and D11S132/NCAM. A new Monte Carlo method for computing approximate location scores estimates this location as being at least 10(8) times more likely than the next most likely interval, with a support interval midway between STMY and D11S132 that is either 5.2 cM (sex averaged and conservatively based on 3 lod scores from the maximum-location score) or 2.8 cM (male specific, based on a 2.72:1 interval-specific female-to male distance ratio. PMID- 1746556 TI - Prenatal hemoglobinopathy screening. IV. Follow-up of women at risk for a child with a clinically significant hemoglobinopathy. AB - To determine the benefits and burdens of prenatal hemoglobinopathy carrier identification and genetic counseling and its impact on subsequent reproductive behavior, we recontacted women whom we had previously identified as at risk for having a child with a clinically significant hemoglobinopathy, regardless of whether they had accepted the offer of prenatal diagnosis. Of the 46 such women, 31 were available for interview. These 31 women had received offers of prenatal diagnosis in 47 pregnancies. Seventeen had been accepted, and 30 had been declined. The proportion of patients accepting the offer of prenatal diagnosis was higher for the index pregnancy (50%) than for subsequent pregnancies (22%). The mean interval between the initial counseling of the patient and the follow-up interview was 43 mo (standard error +/- 2.7 mo). Ninety-four percent of those interviewed recalled having received information from the screening program; 74% recalled the name of their condition; 90% knew that trait did not affect their health; 84% recalled the name of the condition for which their fetus had been at risk; and 77% could state at least one symptom of the disease. Of the 29 women asked whether they intended to use prenatal diagnosis in future pregnancies, 13 said yes and 16 said no. Of the 26 patients asked about satisfaction with their previous decision about prenatal diagnosis, all were satisfied with their decision. Eighteen said they would make the same decision in their next pregnancy, but seven patients said they would not, and one was undecided.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746557 TI - Identification of a single missense mutation in the adenine phosphoribosyltransferase (APRT) gene from five Icelandic patients and a British patient. AB - We have completely sequenced the adenine phosphoribosyltransferase (APRT) gene from each of six patients--five (I-V) from Iceland and one (VI) from Britain. Cases I and II shared a common ancestor six and seven generations ago, and cases I and V shared a common ancestor seven generations ago, but cases III and IV were unrelated to the above or to each other, over seven generations. Genomic DNA was amplified by PCR, subcloned into M13mp18, and sequenced. Genomic and PCR amplified DNAs were also analyzed by restriction-enzyme digestion and Southern blotting. The same missense mutation was identified in all six patients. This mutation leads to the replacement of asp (GAC) by val (GTC), at amino acid position 65. The gene sequences from all patients were otherwise identical to our wild-type sequence. The homozygous nature of the mutation was confirmed by sequencing the PCR product directly. All six patients were homozygous for the 1.25-kb TaqI RFLP. The Icelandic patients were also homozygous for the 8-kb SphI RFLP, but the British patient was heterozygous at this site. These studies suggest that a founder effect is likely to be responsible for APRT deficiency in the Icelandic population. The finding of the same mutation in a patient from Britain suggests that this mutation may have originated in mainland Europe. PMID- 1746558 TI - Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)n repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26). AB - We recently reported a new X-linked mental retardation (XLMR) disorder in a four generation family of Dutch descent. Features included Dandy-Walker malformation, basal ganglia disease, and seizures. Twenty-six family members, including two living affected males and two obligate carriers, were available for study. No evidence of linkage was observed between the disease locus and RFLPs from several X-chromosome regions, including Xp21-p22 (13 markers), proximal Xq (four markers), and Xq28 (three markers). However, a new hypervariable short tandem repeat (STR) within the HPRT gene at Xq26 showed positive linkage to the disease locus, with a maximum lod score of 2.19 at a recombination fraction of 0. A second hypervariable marker in Xq26, the dinucleotide repeat XL90A3 (DXS425), showed a lod score of .84 at a recombination fraction of .11. Both the HPRT and DXS425 markers were typed in 40 CEPH families, and subsequent multipoint linkage analysis showed the following order: Xcen-DXS425-(HPRT,XLMR)-F9-qter. HPRT and these flanking markers are therefore useful for carrier detection and prenatal diagnosis in this family. This study illustrates that hypervariable STRs will be powerful tools for linkage analysis and genetic diagnosis, particularly when relatively small families are involved. PMID- 1746559 TI - A random walk method for computing genetic location scores. AB - Calculation of location scores is one of the most computationally intensive tasks in modern genetics. Since these scores are crucial in placing disease loci on marker maps, there is ample incentive to pursue such calculations with large numbers of markers. However, in contrast to the simple, standardized pedigrees used in making marker maps, disease pedigrees are often graphically complex and sparsely phenotyped. These complications can present insuperable barriers to exact likelihood calculations with more than a few markers simultaneously. To overcome these barriers we introduce in the present paper a random walk method for computing approximate location scores with large numbers of biallelic markers. Sufficient mathematical theory is developed to explain the method. Feasibility is checked by small-scale simulations for two applications permitting exact calculation of location scores. PMID- 1746560 TI - Consistent linkage of the long-QT syndrome to the Harvey ras-1 locus on chromosome 11. AB - The long-QT syndrome (LQT; Ward-Romano syndrome) is a cardiac disorder that is inherited as an autosomal dominant trait. Affected family members suffer from recurrent syncope and sudden death due to ventricular arrhythmias. Recently, we identified a DNA marker on the short arm of chromosome 11 (the Harvey ras-1 locus [H-ras-1]) that was completely linked to the LQT locus in one large family. In the study presented here, we performed linkage investigations on six new and unrelated families with LQT. The LQT locus was again completely linked to the H ras-1 locus in all families examined, with a combined lod score of 5.25 at a recombination fraction of 0. This work confirms our previous assignment of the LQT locus to chromosome 11p and supports the hypothesis that LQT is genetically homogeneous. As no obligate recombinants were identified in either this or our previous study, the H-ras-1 protooncogene remains a candidate for the LQT disease gene. Identification of LQT families with locus homogeneity is an important step in the development of a refined genetic map of this locus and will help determine whether the H-ras-1 marker would be of general use for presymptomatic diagnosis of this potentially fatal, but treatable, disorder. PMID- 1746561 TI - Adrenoleukodystrophy: a complex chromosomal rearrangement in the Xq28 red/green color-pigment gene region indicates two possible gene localizations. AB - We have characterized a complex chromosomal rearrangement in band Xq28, in an adrenoleukodystrophy patient who also has blue-cone monochromacy. A 130-kb region upstream from the color-vision pigment genes was isolated as yeast artificial chromosome or cosmid clones. Another Xq28 sequence, not included in the above region, was obtained by cloning a deletion breakpoint from the patient. Using probes derived from the cloned sequences, we have shown that the rearrangement affects the color-pigment genes and includes two deletions, most likely separated by a large (greater than 110-kb) inversion. One deletion encompasses part of the pigment gene cluster and 33 kb of upstream sequences and accounts for the patient's blue-cone monochromacy. If this rearrangement also caused ALD, the disease gene would be expected to lie within or close to one of the deletions. However, deletions were not detected in a 50-kb region upstream of the red-color pigment gene in 81 other ALD patients. Two CpG islands were mapped, at 46 and 115 kb upstream from the pigment genes. PMID- 1746562 TI - Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12. AB - The gene for Batten disease (CLN3) has been mapped to human chromosome 16 by demonstration of linkage to the haptoglobin locus, and its localization has been further refined using a panel of DNA markers. The aim of this work was to refine the genetic and physical mapping of this disease locus. Genetic linkage analysis was carried out in a larger group of families by using markers for five linked loci. Multipoint analysis indicated a most likely location for CLN3 in the interval between D16S67 and D16S148 (Z = 12.5). Physical mapping of linked markers was carried out using somatic cell hybrid analysis and in situ hybridization. A mouse/human hybrid cell panel containing various segments of chromosome 16 has been constructed. The relative order and physical location of breakpoints in the proximal portion of 16p were determined. Physical mapping in this panel of the markers for the loci flanking CLN3 positioned them to the bands 16p12.1----16p12.3. Fluorescent in situ hybridization of metaphase chromosomes by using these markers positioned them to the region 16p11.2-16p12.1. These results localize CLN3 to an interval of about 2 cM in the region 16p12. PMID- 1746563 TI - Interpreting nonsignificant outcomes of heterogeneity tests in gene mapping. PMID- 1746564 TI - Locked storage of refrigerated controlled substances. PMID- 1746565 TI - Resolving problems in the use of omeprazole. PMID- 1746566 TI - Do we know what we are really looking for? PMID- 1746567 TI - The theory of ADD-MORE. PMID- 1746568 TI - Pharmacists should initiate as well as prevent. PMID- 1746569 TI - Comment on stability of ranitidine hydrochloride in total nutrient admixtures. PMID- 1746570 TI - Pharmacy manager need not be pharmacist. PMID- 1746571 TI - Upgrading quality assurance for pharmacy-prepared sterile products. PMID- 1746572 TI - ASHP invitational conference on quality assurance for pharmacy-prepared sterile products. PMID- 1746573 TI - National survey of quality assurance activities for pharmacy-prepared sterile products in hospitals. AB - The results of a survey of pharmacy department activities for quality assurance in the preparation of sterile drug products in short-term, nonfederal hospitals are reported. A questionnaire was mailed in March and April 1991 to pharmacy directors at hospitals that had indicated in ASHP's 1990 national survey of pharmaceutical services that they had formal quality assurance processes for intravenous admixture preparation. The adjusted gross sample size was 465. The net response rate was 71% (330 usable replies). Nearly all respondents indicated that sterile drug products were prepared extemporaneously in their departments; 61% reported batch preparation of such products. Both pharmacists and pharmacy technicians prepared sterile products. Respondents identified which guidelines were used in developing departmental policies and procedures for sterile product preparation. Specific areas were identified in which educational programs for pharmacists are needed; the most frequently indicated area (85%) was principles of aseptic technique. A majority of respondents used the following means for the orientation and training of personnel who prepare sterile products: aseptic technique lectures or videotapes, on-the-job training, written policies and procedures, and direct observation of technique. Almost all of the respondents (99%) had laminar-airflow hoods in their departments. Three fourths of those respondents indicated that laminar-airflow hoods were located in a limited-access room. Half of the respondents reported that laminar-airflow hoods were located certified every six months and that prefilters were changed monthly. Less than one third sampled environmental areas for microbial contamination. Less than one third of the surveyed hospitals routinely sampled sterile products for microbial contamination or pyrogens. Almost half indicated the absence of policies and procedures for testing chemical purity, drug concentration, sterility, pyrogenicity, or the environment for sterile preparations. Few respondents indicated the use of sterilization techniques other than microbial filtration, which was used by 32% of pharmacies involved in extemporaneous preparation and 16% of those involved in batch preparation. About 90% of the respondents used published references and manufacturers' recommendations to determine expiration dating. This survey revealed that certain quality assurance procedures related to pharmacy-prepared sterile products need major improvement. PMID- 1746574 TI - Sterility testing of antimicrobial-containing injectable solutions prepared in the pharmacy. AB - The need for sterility testing of antimicrobial-containing injectable solutions is discussed and specific testing methods are described. Despite their antimicrobial activity, antimicrobial-containing injectable drug products are not necessarily self-sterilizing and can become contaminated. In addition to practicing aseptic technique, pharmacists must perform end-product sterility testing on intravenous solutions to ensure their sterility. The United States Pharmacopeia provides guidelines for the performance and validation of two sterility test methods: membrane filtration and direct transfer to culture media. Membrane filtration is the method of choice for sterility testing of many antimicrobial-containing injectable solutions. After the test article is filtered, the membrane is rinsed with sterile fluid to remove residual antimicrobial agent, cut into two portions, and immersed in two types of culture medium. Visible turbidity of a sample within the appropriate incubation period indicates the presence of a contaminating microorganism. Closed filtration systems minimize false-positive results. In the direct transfer method, samples of the test article are directly inoculated into vessels of culture media, and antimicrobial activity is eliminated by dilution or by deactivation with chemical or enzymatic agents. Sterility testing as well as aseptic technique is needed to ensure the sterility of antimicrobial-containing injectable solutions. PMID- 1746575 TI - Sterility testing of a total nutrient admixture with a biphasic blood-culture system. AB - The ability of a biphasic blood-culture system to detect microbial contamination of a total nutrient admixture (TNA) was studied. A TNA consisting of amino acids, dextrose, lipid emulsion, electrolytes, and trace elements was prepared under aseptic conditions. Septi-Chek blood-culture bottles were then injected with a TNA sample and with one of various dilutions of five bacterial or fungal suspensions, and an agar slide unit was attached to each bottle. One bottle was injected only with a TNA sample. The bottles were incubated and examined once daily. Each bottle was inverted immediately after inoculation and at each observation time to allow the broth to wash over the agar slide unit. Because the lipid contained in the TNA caused the broth in all bottles to become turbid, it was impossible to determine whether microbial growth was present in the broth. Microbial growth, however, became evident in 24-72 hours on all slide units except the one attached to the bottle that had been injected only with TNA. The Septi-Chek biphasic blood-culture system appears to be useful in evaluating the sterility of TNAs. PMID- 1746576 TI - Method for evaluating drip-rate accuracy of intravenous flow-regulating devices. AB - The effects of patient movement and position on the drip-rate accuracy of several i.v. flow-regulating devices were investigated. Intravenous infusion sites were established in 20 healthy adult volunteers. All the subjects received 5% dextrose injection through the same type of i.v. tubing from 500-mL bags hung from standard i.v. fluid poles. The flow-regulating devices tested were the IVAC 280, which served as the control device; a roller clamp; the Dial-A-Flo; the Exacdrop; and the 3M IV Flow Regulator. Drip rates were present at 40 drops/min and were measured before and after the subjects moved among the supine, sitting, and standing positions and walking. The drip rate was reset to 40 drops/min after each position change. Changing position from supine to sitting did not affect mean drip rates for the IVAC 280 and 3M IV Flow Regulator devices but significantly decreased the rates for the roller clamp, Dial-A-Flo, and Exacdrop. The change from sitting to standing did not affect the IVAC 280 and 3M IV Flow Regulator drip rates but significantly decreased the rates for the other devices. None of the rates was dramatically affected when the subjects went from standing to walking, although the effect achieved significance for the roller clamp and Exacdrop devices. The change from walking to the supine position did not affect the drip rates for the IVAC 280 and 3M IV Flow Regulator but significantly increased the rates for the other devices. The drip-rate accuracy of the roller clamp, Dial-A-Flo, and Exacdrop devices was significantly affected when subjects changed positions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746577 TI - Irreversibility of procainamide-dextrose complex in plasma in vitro. AB - The extent to which the procainamide-dextrose complex reverts to free procainamide hydrochloride in plasma was studied in vitro. The procainamide dextrose species was formed, isolated using preparative liquid chromatography, and then added to six different lots of pooled plasma that were maintained at physiological temperature (37 +/- 0.1 degrees C). At zero, four, and eight hours after preparation of the samples, 1-mL portions were removed from each sample, extracted, and assayed for procainamide hydrochloride using high-performance liquid chromatography. The mean procainamide hydrochloride concentrations at zero, four, and eight hours after preparation were 2.67, 4.81, and 1.38 g/mL, respectively. Each lot of pooled plasma was statistically analyzed to determine if a significant amount of procainamide hydrochloride reappeared. Analysis of variance showed significant difference between the concentrations of free procainamide hydrochloride in the samples at zero, four, and eight hours (p less than 0.02). Follow-up with Duncan's multiple comparisons test determined that the mean procainamide hydrochloride concentrations immediately after preparation were not significantly different from those at eight hours, but the mean procainamide hydrochloride concentrations at four hours were significantly different from those at eight hours (p less than 0.01). A paired Student's t test comparing the data from zero and eight hours showed a significant reduction in mean procainamide hydrochloride concentrations with time (p less than 0.05). The procainamide-dextrose complex in vitro does not revert to free procainamide hydrochloride in plasma at physiological temperature during the first eight hours. PMID- 1746578 TI - Stability of amphotericin B in four concentrations of dextrose injection. AB - The stability of amphotericin B in 5%, 10%, 15%, and 20% dextrose injection was investigated. The dextrose solutions were prepared in triplicate from sterile water for injection and 70% dextrose injection and placed in empty 50-mL polyvinyl chloride bags. The pH of each solution was determined before amphotericin B was added to a concentration of approximately 100 micrograms/mL. The bags were stored at 15-25 degrees C and protected from light. Three 1-mL samples were taken from each bag at various times up to 24 hours. One sample was analyzed for precipitation and color and pH changes. Two samples were analyzed in duplicate by stability-indicating high-performance liquid chromatography. No visual changes were observed, and pH did not change substantially. The mean amphotericin B concentration was greater than 90% of the initial concentration at each sampling time. However, the drug concentration in 3 of the 27 samples from the admixtures with 10% dextrose injection and 5 of the 27 samples from the admixtures with 20% dextrose injection fell below 90% of the initial concentration. Amphotericin B 100 micrograms/mL was stable in 5%, 10%, 15%, and 20% dextrose injection when stored for up to 24 hours at 15-25 degrees C and protected from light. PMID- 1746579 TI - Medicare and Medicaid fraud and abuse regulations. AB - Specific business arrangements that are protected under legislation and regulations governing parties doing business with Medicare or Medicaid are discussed. Regulations implementing the Medicare and Medicaid Patient Protection Act of 1987 specify practices and activities that are not subject to criminal penalties under the antikickback provisions of the Social Security Act or to exclusion from Medicare or state health-care programs. As of July 29, 1991, all organized health-care settings that receive payments from either Medicare or state health-care programs must comply with these regulations. The final rule sets forth "safe harbors"--exceptions to prohibitions against (1) kickbacks, bribes, rebates, and other illegal activities involving remunerations for patient referrals and (2) inducements to purchase or lease goods paid for by Medicare or state health-care programs. The safe harbors comprise 11 broad categories- investment interests, space rental, equipment rental, personal services and management contracts, purchase of a medical practice, referral services, warranties, discounts, employees, group purchasing organizations, and waiver of deductibles and coinsurance. Implications for pharmacy are discussed. These regulations will affect the purchase of pharmaceuticals by institutional pharmacies. Each institution should review its current practices to determine whether they are within the safe harbors. PMID- 1746580 TI - Guidelines for the preparation of sterile ophthalmic products. PMID- 1746581 TI - Impact of treatment guidelines on the use of aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia. PMID- 1746582 TI - Visual compatibility of indomethacin sodium trihydrate with drugs given to neonates by continuous infusion. PMID- 1746583 TI - Cardioplegia solutions. AB - The mechanism of action, characteristics and components, dosage and administration, and adverse effects of cardioplegia solution are described. The pharmacist's role in the formulation, preparation, and quality control of cardioplegia solution is also discussed. The use of cardioplegia solution has substantially increased the safety of cardiac surgery. It protects the myocardium by inducing a rapid and complete diastolic arrest, minimizing myocardial energy requirements and preventing ischemic damage during the arrest phase, and minimizing or preventing reperfusion injury once coronary blood flow is restored. Chemical components added to the cardioplegia solution, such as potassium and glucose, are largely responsible for this protective effect. Basic characteristics of cardioplegia solutions include temperature, osmolarity, and pH. Crystalloid solution has traditionally been used as a vehicle for cardioplegia solution; however, laboratory and clinical studies have demonstrated favorable effects of blood-based cardioplegia solution. Single-pass and recirculating delivery systems can be used to administer either crystalloid or blood cardioplegia solutions. Pharmacists can play a major role in the formulation, preparation, distribution, and quality control of cardioplegia solutions; these solutions prevent myocardial injury during the arrest and reperfusion phases of cardiac surgery. PMID- 1746584 TI - Epidural analgesia. AB - The process of nociception, the anatomy of the epidural space, and the placement of the epidural catheter are reviewed, and the pharmacology and pharmacokinetics, analgesic efficacy, and potential adverse effects of epidurally administered narcotics and local anesthetics are discussed, as well as patient monitoring standards and solution preparation guidelines for these agents. The epidural space is located between the dura mater (the outer-most membrane surrounding the spinal cord) and the vertebral canal. The site of catheter placement is determined by the dermatomes corresponding to the site of desired analgesia. The primary factors that differentiate epidural narcotics are related to their pharmacokinetic profiles. Morphine, which is hydrophilic, has a slower onset of action and a longer duration of analgesia than lipophilic compounds such as fentanyl; morphine also results in less segmentalization (the degree to which analgesia is limited to discrete dermatomal segments corresponding to the level of the epidural narcotic injection) than is seen with lipophilic compounds. Studies have shown that epidural narcotics provide superior pain relief compared with systemic narcotics. Common adverse effects associated with therapeutic doses of intraspinal narcotics include itching, nausea and vomiting, urinary retention, and sedation; respiratory depression is uncommon after epidural administration of narcotics. The most bothersome adverse effect encountered with analgesic doses of local anesthetics is paresthesia. Solutions for epidural administration must be sterile and preservative free. Epidural administration of narcotics and local anesthetics seems to provide better pain relief than conventional methods but may be associated with more bothersome adverse effects. PMID- 1746585 TI - Pediatric pharmacy practice guidelines. Pediatric Pharmacy Administrative Group Committee on Pediatric Pharmacy Practice. AB - Pediatric patients are unique because of age-specific differences in metabolic capacity, disease processes that may make commercially available pharmaceutical preparations unacceptable for use, a lack of published information on the effects of many new pharmacotherapeutic agents in this population, and changes in population demographics caused by new diseases (e.g., AIDS) and new technologic applications. Comprehensive pharmaceutical services are essential for maximizing the benefits--while avoiding or minimizing adverse effects--of pharmacotherapy and new technologies. Comprehensive pharmaceutical services can help maximize the use of health-care resources in the pediatric population and assist in the development, implementation and evaluation of new methods of treatment that will benefit children everywhere. PMID- 1746586 TI - Megestrol acetate in AIDS-related cachexia. PMID- 1746587 TI - Antiretroviral activity of naloxone and naltrexone. PMID- 1746588 TI - Proceedings of a symposium. Acquired factor VIII inhibitors in the nonhemophiliac: historical perspectives, and future approaches. November 30, 1990, 32nd American Society for Hematology Annual Meeting Boston, Massachusetts. PMID- 1746589 TI - An introduction to factor VIII inhibitors: the detection and quantitation. AB - Spontaneous development of autoantibodies against factor VIII:C (FVIII:C) protein in a nonhemophiliac is a rare but significant clinical occurrence that frequently is associated with life-threatening hemorrhagic complications. These autoantibodies often arise as an epiphenomenon of various disease states that are autoimmune or manifest a component of immune dysfunction. The present symposium reviews the immunochemistry of FVIII:C auto-antibodies and describes ways in which this knowledge has been applied to gain insight into the structure-function relationship of the FVIII:C protein. Also discussed are the etiology and natural history of acquired FVIII:C inhibition as well as evolving approaches to its treatment. Therapeutic options for this condition continue to expand, and choice of the optimal regimen for each patient is based on many considerations, including the level of the inhibitor, the underlying disease state, clinical responses to previous treatment, and degree of antibody interaction with heterologous purified FVIII:C protein. Acquired FVIII:C autoantibodies isolated from nonhemophiliacs are characterized as heterogeneous, noncomplement-fixing, nonprecipitating immunoglobulins directed against functional epitopes (antigenic sites) of FVIII:C in a time- and temperature-dependent manner. The clinical significance of these inhibitors is determined qualitatively by studying in vivo survival of FVIII:C activity with infused replacement materials or quantitatively by laboratory mixing tests that measure the capacity of the inhibitor to neutralize FVIII:C activity. In the United States inhibitor potency is expressed most commonly in Bethesda Units (BU), where 1.0 BU is the reciprocal dilution of patient test plasma, permitting detection of 50% residual FVIII:C activity in a mixture with normal pooled plasma. In Europe, FVIII inhibitors are now often quantitated in New Oxford Units, which are derived from neutralizing-mixing studies of patient test plasma with diluted FVIII concentrate. One Oxford unit is equivalent to approximately 0.83 BU. Although analyses that measure functional inhibition of FVIII:C activity by the autoantibody provide a useful tool to assess clinical efficacy of therapeutic regimens, these assays may not recognize nonactivating antibodies. These immunoglobulins may bind to alternative epitopes and significantly influence plasma clearance, survival times, and circulating levels of infused FVIII:C protein. Finally, this symposium will speculate on the potential application of innovative approaches to inhibitor therapy, based on results from numerous provocative studies on the nature of the human immune response. PMID- 1746590 TI - Cytotoxic suppression of acquired factor VIII:C inhibitors. AB - Autoantibodies directed against factor VIII:C (FVIII:C) are associated with serious and often fatal bleeding. Efforts to suppress or abolish these antibodies with cytotoxic agents are frequently successful if antibody titer is not too high or there is an associated disease that undergoes remission. Corticosteroids alone may hasten antibody disappearance in almost half of patients, and cyclophosphamide is useful in those who are resistant to steroids administered alone or in combination. Patients refractory to these regimens may respond to a more aggressive approach using combination chemotherapy with cyclophosphamide, prednisone, and vincristine. Unfortunately, because of the rarity of this disorder, randomized, controlled trials have not been conducted either to compare treatments directly or to examine the factors presaging favorable outcomes. Recently, however, a multicenter trial comparing prednisone, cyclophosphamide, and the combination has been initiated, and some preliminary data from this investigation are presented. Approaches to the recognition and clinical management of this disorder also are described. PMID- 1746591 TI - Rationale and evolution of therapy with porcine factor VIII:C. AB - Highly purified porcine factor VIII:C (FVIII:C) concentrate prepared by polyelectrolyte fractionation has been available for therapeutic use since 1980. Over the last decade substantial international experience has confirmed the value of porcine FVIII:C in management of hemophilia with inhibitors, and recent studies have underlined its particular effectiveness in treating patients with the acquired form of the disease. The rationale for use of porcine FVIII:C is based on a twofold premise. First, most inhibitors interact less strongly with porcine FVIII:C than they do with the human factor; cross-reactivity is especially low, and often negligible, among patients with acquired disease. Second, when measurable levels of circulating FVIII:C can be achieved, the likelihood of clinical hemostasis is maximized. In a variable proportion of patients with the congenital disease, anamnestic rises in titers of the inhibitor against human FVIII:C may follow treatment with the porcine factor, and this phenomenon may constrain therapy. These events seem to occur rarely in persons with acquired inhibitors, however, thus broadening therapeutic application of porcine FVIII:C to these patients. Although anamnesis often is perceived as a limitation, significant untoward transfusion reactions are highly unusual after porcine FVIII:C therapy. Although early experience with this form of treatment centered on management of major bleeding episodes and hemostatic crises, use of porcine FVIII:C has more recently been extended to more routine bleeding problems, immune tolerance induction regimens, prophylaxis, and home therapy. These and other advances are discussed. PMID- 1746592 TI - The use of porcine factor VIII in the treatment of patients with acquired hemophilia: the United Kingdom experience. AB - Data have been collected by questionnaire on 15 acute bleeding episodes in 12 patients with acquired hemophilia, treated with porcine factor VIII (FVIII). The median initial anti-human FVIII inhibitor level was 40 Bethesda Units (BU)/ml, whereas that against porcine was 1 BU/ml. The mean initial dose of porcine FVIII infused was 54 micrograms/kg, which resulted in a rise of 0.57 IU/mL in the FVIII concentration. Therapy was continued for a mean of 8.5 days, during which time the average number of infusions was 11. Clinical response was rated as good or excellent in 82% of recipients. Side effects were uncommon; only one patient experienced a severe reaction. Following therapy, no increase in antihuman antibody levels was noted; increased levels of antiporcine antibody was detected in only two patients. One patient bled on three further occasions and was successfully retreated with porcine FVIII. Porcine FVIII is a safe and clinically effective treatment for bleeding episodes in acquired hemophilia and should be considered as first-line therapy for patients with low antiporcine FVIII levels. PMID- 1746593 TI - Innovative use of porcine factor VIII:C for immune tolerance induction. AB - Of all nonhemophilic patients with acquired factor VIII:C (FVIII:C) inhibitors, as many as 87% suffer from hemorrhagic complications, and approximately 22% die as a result. Immunosuppressive therapy reduces or eradicates the inhibitor in 50 80% of patients, but a significant proportion remain refractory to such treatment and have a continued need for replacement therapy to manage bleeding complications. The possibility that porcine FVIII:C might fulfill this role has not been thoroughly investigated although limited data are available for patients with congenital hemophilia, which may offer some guidance. We recently reported the successful treatment with porcine FVIII:C over 2-8.5 years in five congenital hemophilia patients with high-level inhibitors initially lacking measurable cross reactivity to porcine FVIII:C. One of four patients who developed transient, specific antiporcine inhibitors became refractory to treatment. Three further patients' antibodies demonstrated as much as 30% cross-reactivity but tolerated porcine FVIII:C therapy on demand for 18-24 months, with good clinical effect and no significant anamnesis or other untoward reactions. All five of these patients with non-cross-reacting antibodies began therapy with porcine FVIII:C and eventually lost their original inhibitors against human FVIII:C during treatment with the porcine factor. Surprisingly, when human FVIII:C was then reintroduced in three patients there was no recurrence of inhibitor activity during 3-4 subsequent years. This finding suggests that porcine FVIII:C, when administered over some interval to congenitally hemophilic patients, can induce a state of specific immune-tolerance to the human factor. On the other hand, porcine FVIII:C therapy may not suppress acquired inhibitors in nonhemophiliacs, since there is no evidence that administration of human FVIII:C causes immune-tolerance in this group. Porcine FVIII:C can be administered safely for a period of years. Anamnestic responses are unusual in acquired hemophilia, and only 20% of patients develop specific antiporcine antibodies. Porcine FVIII:C may play an important part in the long-term management of inhibitors in either congenital or acquired hemophilia. PMID- 1746594 TI - Perspectives on the use of factor IX complex concentrates in the treatment of bleeding in persons with acquired factor VIII inhibition. AB - In contrast to the type of bleeding encountered in congenital hemophilia with inhibitors, the diathesis toward bleeding exhibited by patients with spontaneously acquired factor VIII (FVIII) inhibitors often is severe and life threatening. Large hematomas and retropharyngeal or central nervous system hemorrhage may appear suddenly. Thus, a high premium is placed on rapid therapeutic intervention. Several treatment options are at the physician's disposal. The role of factor IX (FIX) complex concentrates, both standard and purposely activated, is discussed. The FIX products are also known as prothrombin complex concentrates (PCCs). Prudent choice of any treatment modality requires weighing its benefits and shortcomings. Advantages of PCCs--particularly the activated products--include availability, ease of reconstitution and administration, and at least partial efficacy; control of bleeding episodes can be achieved with PCCs in many (but not all) instances. One salient disadvantage of therapy with FIX complex concentrates is that they are not subjected to such rigorous viral-attenuation processes as are most of the currently marketed FVIII products. Therefore, a small but definite risk of infection with hepatitis B or C (HBV, HCV) remains. An assay that detects antibodies against HCV has been licensed and is being used to screen blood donors. Nevertheless, up to the present time the U.S. Food and Drug Administration (FDA) has ruled that HCV screening of plasmapheresis donors should not be performed for plasma collections destined to be pooled for fractionation and that units of HCV-positive source plasma (e.g., that provided by American Red Cross donors) found to be HCV positive be sent for fractionation. The starting plasma from which FIX complex concentrates and human FVIII concentrates are made thus contains some HCV and may also contain some HBV. Because nonhemophiliacs with acquired antibodies against FVIII are unlikely to have had prior exposure to blood products and are unlikely to have been vaccinated against HBV, they are at risk of viral hepatitis and its sequelae when treated with FIX complex concentrates. Furthermore, therapy with FIX complex concentrates is not always effective in controlling bleeding in persons with FVIII inhibitors, its mechanism of action in bypassing the need for FVIII remains unclear, very large doses are required, and it has an attendant risk of several adverse effects when used in large, repeated doses. These include disseminated intravascular coagulation, thromboembolism, and acute myocardial infarction. Thus, FIX complex concentrates may play a useful role in the treatment of bleeding in nonhemophiliacs with acquired inhibitors against FVIII, but one must carefully consider their disadvantages profile.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1746595 TI - Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors. AB - Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender. PMID- 1746596 TI - Future approaches to factor VIII inhibitor therapy. AB - Future progress in our ability to treat acquired factor VIII (FVIII) inhibitors must be based on advances in knowledge of both the FVIII molecule and the nature of the human immune response. New therapeutic approaches to patients with acquired FVIII inhibition likely will emphasize modifications of the immune response. This concept holds considerable promise, because studies have characterized the critical steps leading to tolerance of self-antigens. Development of FVIII inhibitors represents a loss of self-tolerance, which any successful therapy must restore. Conceivably, restoration of self-tolerance can be accomplished in many ways: prevention of antigen binding to helper T lymphocytes, deletion of self-antigen-reactive T cells, inhibition of major histocompatibility complex (MHC) recognition, or enhancement of the antigen specific suppressor T lymphocyte population. Recent data have demonstrated that highly specific methods can suppress ongoing immune responses against defined autoantigens. Antibodies that inhibit T-cell activation, peptides that block self antigen binding, and antibodies that inhibit MHC recognition all have been successful in modifying experimentally induced autoimmune diseases. Whether any of these immunotherapeutic approaches will be effective in the treatment of acquired FVIII inhibition remains to be determined. Until data from animal model systems establish the feasibility of immune intervention, scrutiny of other new therapeutic approaches to patients with spontaneous inhibitors will continue to be important. Administration of FVIII-bypassing procoagulant proteins shows promise, as does removal of inhibitors by affinity reagents, such as FVIII peptides containing relevant epitopes (antigenic sites). Farther on the horizon is development of recombinant FVIII molecules so modified as to remove antigenic determinants while preserving procoagulant function. Articles in this supplement summarize several avenues for treatment of patients with acquired FVIII inhibitors. Alternatives include treatment with sufficient human or porcine FVIII to offset inhibitors, use of materials that reestablish hemostasis even though FVIII levels are not increased (the so-called FVIII-bypassing agents), manipulation of immune responses through physical depletion of inhibitor by plasmapheresis or affinity chromatography, and administration of intravenous immunoglobulin or immunosuppressive cytotoxic drugs. Thus, the heterogeneous clinical presentation is paralleled by the wide range of available therapeutic approaches. PMID- 1746597 TI - Acquired inhibitors in malignant and nonmalignant disease states. AB - Acquired inhibitors against factor VIII:C (FVIII:C) arise in nonhemophilic patients who have many associated disease states, both malignant and benign. This review emphasizes knowledge of the association with malignant diseases and places particularly close attention on the hematologic malignancies, including plasma cell dyscrasias and lymphoproliferative disorders. Characteristics of postpartum inhibitors are examined, as well as the association of inhibitor with certain drugs and dermatologic conditions. Also discussed is the experience amassed by one center over the past decade in the treatment of patients with inhibitors against FVIII:C. PMID- 1746598 TI - Premutation for the Martin-Bell syndrome analyzed in a large pedigree segregating also for G6PD-deficiency. I: A working hypothesis on the nature of the FRAX mutations. AB - A large Sardinian family including 13 Martin-Bell syndrome (MBS) patients, several instances of normal transmitting males or females, and the G6PD Mediterranean mutant segregating in some of its branches, has been thoroughly investigated with the hope of gaining further insight on the nature of the FRAX mutation. All the MBS patients and the 15 obligate heterozygous women present in the pedigree could be traced back through their X-chromosome lineage to the same ancestress, who must have been heterozygous for a silent premutation at the FRAX locus. This premutation appears to have turned into a true FRAX-mutation at least 9 times during the gametogenesis of the ancestress' X-related descendants of whom four are males. This finding alone suggests that the transition from the FRAX premutation to the true mutation can be the result of intra- as well as interchromosomal events. This conclusion is supported by the additional observation that the genetic phase between the FRAX and the G6PD loci remained unaltered when the transition occurred in a repulsion double heterozygote for the premutation and the G6PD-Mediterranean mutant. The data described are compatible with the hypothesis that MBS patients and normal transmitting males are, respectively, hemizygous for deletion or duplication products generated by aberrant recombination events at a highly recombinogenic site of the region Xq27 Xqter. The overall message stemming from this report is that no firm conclusion can be drawn on the genetic linkage between the FRAX-locus and other markers of this region until the nature of the FRAX-mutations and the mechanism of their occurrence are fully understood. PMID- 1746599 TI - Extending the Pallister-Hall syndrome to include other central nervous system malformations. AB - Hall-Pallister syndrome is defined by specific facial anomalies, post axial polydactyly, imperforate anus, and brain anomalies including a rare diencephalic mass, hypothalamic hamartoblastoma. In this article, two patients are described with the usual features of Hall-Pallister syndrome, including diencephalic anomalies, but without hamartoblastomas. These patients may suggest an appropriate extension of the definition of the Hall-Pallister syndrome. PMID- 1746600 TI - Delayed spontaneous pubertal growth spurt in girls with the Ullrich-Turner syndrome. AB - By means of an appropriate mathematical model (Sager's 2-components-concept) a delayed spontaneous pubertal growth spurt can be demonstrated in girls with 45,X Ullrich-Turner syndrome (UTS) (n1 = 45) as well as in those with 45,X/46,XX mosaicism (n2 = 14) never treated with any growth stimulating drug. On the average, this growth spurt begins later and its extent is smaller (mean growth rate = 3.10 and 2.79 cm, respectively, in the 15th year of chronological age) than in normal girls. The delay in acute growth spurt corresponds very well to the delay of skeletal maturation in the UTS (on the average 2 to 3 years of chronological age). PMID- 1746601 TI - New X-linked syndrome of mental retardation, gynecomastia, and obesity is linked to DXS255. AB - We describe 14 males from 3 successive generations in a family who have X-linked mental retardation (XLMR), obesity, gynecomastia, speech difficulties, emotional lability, tapering fingers, and small feet. Linkage analysis using markers spread along the X chromosome demonstrated a gene localisation close to the centromere. Maximum lod scores for markers near the centromere, all at theta = 0.00, were 1.36 for DXS72, and 1.46 for DXYS1. The closest flanking markers which showed recombination were DXS84 and DXS94, defining the physical localisation within Xp21.1-q22. DXS255 was fully informative with lod-1 confidence interval for theta of 0.00-0.12. Clinical findings and linkage data in this family distinguish it from the Borjeson-Forssman-Lehmann syndrome and other previously described XLMR syndromes. PMID- 1746602 TI - Ectrodactyly, retrognathism, abnormal ears, highly arched palate, spina bifida, congenital heart defect, single umbilical artery. PMID- 1746603 TI - Dominantly inherited syndrome comprising partially absent eye muscles, hydrocephaly, skeletal abnormalities, and a distinctive facial phenotype. PMID- 1746604 TI - Hepatic dysfunction in Alstrom disease. AB - Alstrom disease is a rare disorder; less than 20 cases have been reported. An 11 year-old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alstrom disease. PMID- 1746605 TI - Presymptomatic testing for adult onset polycystic kidney disease in at-risk kidney transplant donors. AB - Autosomal dominant adult-onset polycystic kidney disease (ADPKD) is estimated to have an incidence of 1/1,000 and accounts for approximately 10% of all end-stage renal disease in the United States. While relatives are attractive as renal donors due to their availability and the improved transplant success associated with living-related donors, they may coincidentally be at risk for ADPKD. Accurate presymptomatic testing for at-risk potential donors is critical for both the donor and the recipient. We report here 2 families in which presymptomatic testing for ADPKD was accomplished by DNA linkage analysis on several potential renal donors prior to transplant. This resulted in the protection of both donors and recipients by preventing the transplantation of a kidney affected by ADPKD. Thorough counseling prior to DNA analysis (including discussion of accuracy and possible testing outcomes of presymptomatic diagnosis of ADPKD, diagnosis of noncarrier status, false paternity, and non-informative study) was essential to provide informed consent and preserve confidentiality within the family. Confidentiality for potential donors found presymptomatically to be affected (with a 94% or greater probability) was especially difficult to maintain. PMID- 1746606 TI - Severe anomalies associated with ring chromosome 7. AB - A newborn infant with the polyasplenia sequence, intrauterine growth retardation, cutaneous nevi, and minor anomalies was found to have mosaicism for ring chromosome 7. This patient's anomalies are markedly different from those of previous patients reported with this cytogenetic anomaly. PMID- 1746607 TI - Uniparental disomy, isodisomy, and imprinting: probable effects in man and strategies for their detection. AB - The concept of uniparental disomy--the presence of a chromosome pair derived solely from one parent in a diploid offspring--was introduced in 1980 as a probable consequence of the high rate of germ cell aneuploidy in man, and has now been convincingly demonstrated through molecular analyses in several families. A most likely mechanism for the production of uniparental disomy is the chance reunion, and complementation, of 2 gametes aneuploid for the same chromosome member; uniparental disomy could also occur through other mechanisms including postzygotic non-segregation in a trisomic conceptus. Uniparental disomy may result in isodisomy, i.e., homozygosity of a series of contiguous alleles in a pair of homologues. The presence and degree of isodisomy in an offspring depend in turn on the occurrence, timing, and extent of the meiotic recombination that had occurred in the chromosome pair of the disomic gamete involved. Uniparental disomy with or without isodisomy can explain a number of unusual observations, such as the unexpected pattern of transmission of a genetic disorder. The two may be associated with an imprinting effect to produce pathological phenotypes, as has been observed in the mouse, and may be the basis for a number of syndromes of as yet unclear cause. The evidence for uniparental disomy, isodisomy, and imprinting in man is reviewed, and strategies for their detection presented. PMID- 1746608 TI - Chromosome 7p--syndrome: craniosynostosis with preservation of region 7p2. AB - Deletion of a portion of the short arm of chromosome 7 is associated with a recognizable phenotype which often includes craniosynostosis. Recent reports have suggested that craniosynostosis occurs only if there is a deletion involving band 7p21 or the segment distal to that band. We report on a boy who had an interstitial deletion of 7p, not involving band 7p21 or the segment distal to that band, who nevertheless had craniosynostosis. Thus, it appears that the determination of craniosynostosis in this syndrome is more complicated than has been suggested previously. PMID- 1746609 TI - Opitz trigonocephaly syndrome. AB - We report on a patient with Opitz trigonocephaly syndrome. The girl was the first born child of consanguineous parents and had trigonocephaly, apparent hypertelorism, upslanted palpebral fissures, strabismus, small nose with broad root, abnormally modeled ears, high palate, short neck with loose skin, polysyndactyly, and prominent clitoris and labia majora. In addition, a complex cardiovascular defect (Eisenmenger disease) was observed. The patient was mentally retarded. PMID- 1746610 TI - Hypomelanosis of Ito associated with chromosomal translocation involving Xp11. AB - We report on a 3-year-old girl with hypomelanosis of Ito (HI). She has typical skin lesions and mild CNS involvement characterized by impaired walking and borderline mental retardation. Cytogenetic investigation showed a 18/X translocation with breakpoint on Xp11. This is the sixth case of HI in which this breakpoint has been reported, underlining that this event cannot be considered coincidental. Further studies are needed to understand the etiologic and pathogenetic meaning of this finding. PMID- 1746611 TI - Ring chromosome 15 and 15qs+ mosaic: clinical and cytogenetic behaviour spanning 29 years. AB - A phenotypic female with mild mental retardation, minor facial anomalies, and short stature has been evaluated clinically and cytogenetically over 29 years. At age 59, she remains physically well and shows no signs of dementia. Cytogenetic analysis, performed on peripheral blood specimens on 10 occasions between 1961 and 1990, showed mosaicism with one cell line containing a large stable ring (15) chromosome and another cell line without the ring but with a 15qs+. The different cell lines remained constant. The case provides information on the natural history of the ring chromosome 15 syndrome. PMID- 1746612 TI - Trisomy 9 confined to the placenta: prenatal diagnosis and neonatal follow-up. AB - Chorionic villus sampling (CVS), performed on a woman in the 23rd menstrual week because of bilateral fetal hydronephrosis and suspected intrauterine growth retardation (IUGR), documented trisomy 9 in all cells examined. Chromosomes of amniocytes and fetal blood lymphocytes were normal. The ongoing pregnancy was monitored closely, and at 37 weeks, a phenotypic normal male infant was delivered. Multiple placental biopsies showed 47,XY,+9, while a repeat chromosome analysis of the infant and biopsies from the amniotic membrane were normal (46,XY). This case further emphasizes the association between placental aneuploidy and IUGR. To our knowledge, nonmosaic trisomy 9 in CVS confined to the chorionic villi and later confirmed in the placenta has not been reported previously. PMID- 1746613 TI - San Luis Valley recombinant chromosome 8 and tetralogy of Fallot: a review of chromosome 8 anomalies and congenital heart disease. AB - Tetralogy of Fallot, the most common cyanotic heart defect, has not been closely associated with a specific chromosome defect. The San Luis Valley Recombinant Chromosome 8 [SLV Rec(8)] syndrome is strongly associated with congenital heart disease, particularly tetralogy of Fallot. This article reviews SLV Rec(8) syndrome and other chromosome 8 aberrations to suggest locations for cardiogenic genes. SLV Rec(8) [rec(8),dup q,inv(8)(p23q22)] syndrome has been found in Hispanic families in the southwestern United States. Congenital heart disease is found in 93.3% of SLV Rec(8) individuals (n = 45), with tetralogy of Fallot constituting 40.5% of all lesions and conotruncal defects, 55.6%. These frequencies exceed the incidence of tetralogy of Fallot (10%) and conotruncal defects (20%) among all children with heart defects (P less than 0.003 for both). Review of patients with deletion 8p (n = 13) showed heart defects in 84.6% with 27.3% being conotruncal defects. Among duplication 8q patients (n = 20), 45% had heart defects with conotruncal defects constituting 44%. Neither group differed significantly from expected in its incidence of conotruncal defects. Among patients with mosaic trisomy 8 (n = 47), 12 had heart abnormalities including one conotruncal defect. Among 3 patients with other rec(8) chromosomes, one had a ventricular septal defect. The cause of heart defects in SLV Rec(8) cannot be assigned to either the deletion of 8p or the duplication of 8q. The lack of an association between other chromosome 8 abnormalities and tetralogy of Fallot suggests that genes at the SLV Rec(8) breakpoints or an interaction between genes on both arms of chromosome 8 are important. PMID- 1746614 TI - Retrospective survey of urea cycle disorders: Part 2. Neurological outcome in forty-nine Japanese patients with urea cycle enzymopathies. AB - We analyzed neurological data, including DQ or IQ, EEG, and CT scan, in 49 patients with urea cycle enzymopathies, all of whom were included in a retrospective survey from 1978-1988 in Japan. We classified 3 groups depending on age-at-onset: group 1 (0-28 days, N = 11), group 2 (29 days-5 years, N = 31), and group 3 (greater than 5 years, N = 7). The least DQ or IQ score and the highest CT score, representing the most severe brain damage was found in group 1, and the highest DQ or IQ and the least CT score was found in group 3. Intermediate scores of both parameters were found in group 2. There was a negative correlation between these 2 parameters (r = -0.82, P less than 0.01). Abnormal EEG during the attack-free period was predominantly observed in patients with CT abnormalities compared to those with a normal CT scan (P less than 0.01). Approximately 40% of the patients, mostly in groups 2 and 3 (92.8%) had normal findings in all 3 parameters. Thus, the magnitude of developmental abnormalities is clearly related to the degree of brain damage and to the age-at-onset of these diseases. PMID- 1746615 TI - Autosomal dominant transmission of congenital erythroid hypoplastic anemia with radial abnormalities. AB - We describe a mother and son with congenital hypoplastic anemia. The mother has apparently normal thumbs and forearms but her son has bilateral radial hypoplasia. They provide a further example of dominant inheritance of Diamond Blackfan anemia/Aase syndrome and suggest that thumb and radial abnormalities are a component of this syndrome. PMID- 1746616 TI - Blepharophimosis sequence and de novo balanced autosomal translocation [46,XY,t(3;4)(q23;p15.2)]: possible assignment of the trait to 3q23. AB - We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46,XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the belpharophimosis sequence, based on the comparison of clinical manifestations between 4p- and 3q-syndromes. PMID- 1746617 TI - Neurological aspects of del(1q) syndrome. AB - We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions. PMID- 1746618 TI - Quantitative analysis of associations between birth defects and suspected human teratogens. AB - Case series of infants with certain birth defect patterns and putative teratogenic exposures should be interpreted with caution since the presence of birth defects and the exposure among the same infants could be entirely due to chance. In the absence of other epidemiologic data, the plausibility for a causal association is strengthened by 1) rarity of the defect pattern, 2) rarity of the exposure in the population, 3) small source population, 4) short time period for the study, and 5) biologic plausibility for the association. These concepts are illustrated using case reports of putative teratogenicity of cocaine and etretinate. In the presence of epidemiologic data, the concept of attributable fraction in exposed (AFE) can be used to evaluate the likelihood that the defect pattern among infants with a particular exposure is attributable to the exposure. This quantity is related to the strength of the epidemiologic association between the defect pattern and the exposure, as measured in terms of relative risk R (or odds ratio), and is equal to (R-1)/R. Even for strong teratogens such as maternal diabetes and isotretinoin, where R is about 7, in more than 14% (1-AFE) of exposed infants with birth defects, the pattern of defects is not attributable to the exposure. Furthermore, AFE can be used to "correct" crude measures of sensitivity (the proportion of exposed malformed infants with a defect pattern attributable to the exposure) and positive predictive value (the proportion of malformed infants who have the exposure and have the defect pattern attributable to the exposure).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746619 TI - Absence of fetal cells in maternal circulation at a level of 1 in 25,000. AB - A dual polymerase chain reaction (PCR) technique is developed which enables the detection of one part male DNA in 25,000 parts female DNA. The technique amplifies a part of the X-Y homologous amelogenin gene in which the Y counterpart has a 189 bp deletion within one of the introns. This deletion has made it possible to identify individual X and Y counterparts based on the difference in size between them. None of the 18 pregnant women studied showed a positive Y signal although eight of them bear male fetuses excluding the presence of fetal cells at one in 25,000 maternal cells. The results presented here show that a sensitivity of greater than one in 25,000 is required for detection of fetal genetic disease using maternal peripheral blood. PMID- 1746620 TI - De novo inv(2)(p21q31) associated with isolated bilateral microphthalmia and cataracts. AB - We report on a patient with bilateral microphthalmia and unusual cataracts with a de novo pericentric inversion of chromosome (2)(p21q31). A literature review of previous associations of eye abnormalities and anomalies of chromosome 2 suggests probable gene locations for eye development. PMID- 1746621 TI - "Snail-like pelvis" chondrodysplasia: a further case report. AB - Chondrodysplasia with snail-like pelvis (Schnechenbecken dysplasia) is a rare distinct, lethal, short-limbed dwarfism. We describe the clinical and radiological features of a new case in an Italian family. PMID- 1746622 TI - Risk calculations in the fragile-X syndrome. PMID- 1746623 TI - The illusion of progress. PMID- 1746624 TI - The mental health professional and social action. PMID- 1746625 TI - The prevalence of abuse among homeless and housed poor mothers: a comparison study. AB - The history of physical and sexual abuse among 50 homeless and 50 housed poor mothers was compared, with particular attention to details of prevalence, type, and severity. No significant differences were found except in higher reported rates of sexual abuse in adulthood among housed mothers. However, 89% of the total sample reported experiencing some form of abuse in their lifetimes. The unexpected lack of differential and the high prevalence rates are discussed in terms of service delivery and social policy implications. PMID- 1746626 TI - Caregiver burden: gender and the psychological costs of caregiving. AB - The psychological costs of providing care for a parent with Alzheimer's disease are examined, together with the consequences of depression, anxiety, guilt, and resentment in relation to the caregiver's coping style, social support, and sense of control. The use of fantasy by women as a coping mechanism was associated with greater anxiety and depression, adequate social support was somewhat more helpful for men, and a sense of control was more helpful for women. PMID- 1746627 TI - Acute versus chronic grief: the case of pregnancy loss. AB - Conceptual and measurement problems in identifying those at risk of chronic grief are reviewed, and results are presented of a longitudinal study of people who have experienced pregnancy loss. Coping resources, particularly prior mental health and social support, were the best predictors of low scores on subscales of the Perinatal Grief Scale that indicate chronic grief reactions. Results also offer some evidence of delayed grief responses, especially among men and those who experienced early losses. PMID- 1746628 TI - Preventing birth injury among women in Africa: case studies in northern Nigeria. AB - Among the most serious maternal injuries from childbirth in Africa is vesicovaginal fistula (VVF). Case studies of 55 VVF patients in northern Nigeria showed them to be poor, underage village women without sufficient access to modern health facilities at the time of the injury. Suggestions for short-term and long-term preventive measures are presented and discussed. PMID- 1746629 TI - Statutory emancipation of minors: use and impact. AB - Interviews with 18 adolescents who petitioned for emancipation under a California statute revealed that the decision to seek emancipation was often based on the concerns of adult family members, and that those adults sometimes facilitated the actual legal process. The study also revealed that the statute's prerequisites for emancipation were frequently not fulfilled. PMID- 1746630 TI - The parent-child interview: use in evaluating child allegations of sexual abuse by the parent. AB - The practice of using parent-child interviews to determine whether children have been sexually abused by the parent is called into question. The relevant literature is reviewed, and practical and ethical reasons for eschewing such interviews are discussed. Three case examples in which parent-child interviews were attempted or employed are described and discussed. PMID- 1746631 TI - The frog prince: tale and toxicology. AB - Bufotenin is a substance present in the skin of some common species of frogs, and its ingestion (such as would occur in licking or kissing a frog) can result in vivid hallucinations. This biological property offers an explanation for the portrayal of frogs in folklore as creatures of transformation, or as intermediaries with other worlds. PMID- 1746632 TI - Psychotherapy as an approach to special education prevention: perceptions of student behavior. AB - This study investigated the impact of one year of psychotherapy, used in an attempt to avoid special education referral, on teachers' and psychotherapists' perceptions of student disruptiveness and withdrawal. Results indicated that psychotherapists perceived improvement in both types of behavior, while teachers did not. Possible reasons for this perceptual difference are discussed. PMID- 1746633 TI - Mandated leave: an analysis of federal and state legislation. AB - Results of a survey of federal and state legislation on family and medical leave, based on proposed legislative activities in 1986 and 1987 and on the outcome of these activities from 1986 to 1991, are presented. Major variations in employee provisions and employer protections are outlined and discussed, and likely directions for future legislation identified. PMID- 1746634 TI - The elusive search for certainty in child welfare: introduction. PMID- 1746635 TI - Issues in foster family care: where do we stand? AB - An overview of recent findings about children and families in foster care describes the population, reviews positive and negative results of foster care, and raises such clinical and policy issues as the beneficial outcomes of long term foster care, the economic crisis for foster parents, and the vulnerability of minority children and families. Implications for research are discussed. PMID- 1746636 TI - Whose child is this? Assessment and treatment of children in foster care. AB - Clinicians who treat children in foster care must continually balance the development and therapeutic needs of the foster child with the expectations of a complex network of caretakers and professionals with whom the child interacts. A model that integrates individual and systemic issues in the assessment and treatment of children in foster care is proposed. PMID- 1746637 TI - Child welfare and the role of women: a feminist perspective. AB - Linked by caretaking, the major stakeholders in the child welfare system are women and children. Contrary to general assumption, however, their rights and needs are not equally satisfied by the same service systems. A feminist reanalysis of basic policy aims, and of caretaking roles and functions, is crucial to the development of a more satisfactory child welfare system. PMID- 1746638 TI - The delivery of child welfare services to African American clients. AB - African Americans have historically suffered inequities in the delivery of child welfare services. The necessity for awareness of cultural contexts is examined, particularly in decision making about maintenance in the child's home, out-of home placement, reunification of child and parents, other permanency planning options, and mental health referrals. The implications of such awareness for service delivery, administration, and policy making in the child welfare system are discussed. PMID- 1746639 TI - The optimism of policy choices in child welfare. AB - That the desire for sure answers to problems in child welfare has led to acceptance of programs on the basis of faith rather than realism is illustrated by examination of some current programs. The need for rational choices in policy, program, and practice that respond to the basic human requirements of vulnerable families is highlighted. PMID- 1746640 TI - Crafting a federal legislative framework for child welfare reform. AB - The nature and scope of the problems plaguing child welfare systems across the country make federal solutions especially urgent. A decade after enactment of the Adoption Assistance and Child Welfare Act (PL 96-272), legislation is pending that builds on its framework to enhance services and supports for vulnerable children and their families. The legislation reflects a growing consensus about the nature of the child welfare crisis and about the reform strategies that will be effective. PMID- 1746641 TI - Compact bone distribution and biomechanics of early hominid mandibles. AB - This investigation explores the effects of compact bone distribution on the biomechanical properties of the postcanine mandibular corpus of the fossil hominid taxa Australopithecus africanus and Paranthropus robustus. The mandibles of extant great apes, modern humans, and the fossil hominids are examined by computed tomography (CT), and compact bone contours are used to calculate cross sectional biomechanical properties (cortical area, second moments of area, and Bredt's formula for torsional strength). The relative amount of compact bone is comparable in the modern and fossil mandibles, but the mechanical properties of A. africanus and P. robustus jaws are distinct in terms of the ratio of minimum to maximum second moments of area. This difference most likely represents a structural response to elevated torsional moments in the fossil hominids. Although the relative amount of compact bone in cross-section does not differ significantly between taxa by statistical criteria, A. africanus utilizes less cortical bone than P. robustus in the same manner in which Pongo is separated from the condition in other extant large-bodied hominoids. It has been suggested that the phenomenon of mandibular "robusticity" (expressed as an index of corpus breadth/corpus height) may be an effect of postcanine megadontia and/or reduced canine size in the australopithecines. Results presented here, however, indicate that it is unlikely that either factor adequately accounts for mandibular size and shape variation in early hominids. PMID- 1746642 TI - Increased vital and total lung capacities in Tibetan compared to Han residents of Lhasa (3,658 m). AB - Larger chest dimensions and lung volumes have been reported for Andean high altitude natives compared with sea-level residents and implicated in raising lung diffusing capacity. Studies conducted in Nepal suggested that lifelong Himalayan residents did not have enlarged chest dimensions. To determine if high-altitude Himalayans (Tibetans) had larger lung volumes than acclimatized newcomers (Han "Chinese"), we studied 38 Tibetan and 43 Han residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m) matched for age, height, weight, and smoking history. The Tibetan compared with the Han subjects had a larger total lung capacity [6.80 +/- 0.19 (mean +/- SEM) vs 6.24 +/- 0.18 l BTPS, P less than 0.05], vital capacity (5.00 +/- 0.08 vs 4.51 +/- 0.10 1 BTPS, P less than 0.05), and tended to have a greater residual volume (1.86 +/- 0.12 vs 1.56 +/- 0.09 1 BTPS, P less than 0.06). Chest circumference was greater in the Tibetan than the Han subjects (85 +/- 1 vs 82 +/- 1 cm, P less than 0.05) and correlated with vital capacity in each group as well as in the two groups combined (r = 0.69, P less than 0.05). Han who had migrated to high altitude as children (less than or equal to 5 years old, n = 6) compared to Han adult migrants (greater than or equal to 18 years old, n = 26) were shorter but had similar lung volumes and capacities when normalized for body size. The Tibetans' vital capacity and total lung capacity in relation to body size were similar to values reported previously for lifelong residents of high altitude in South and North America. Thus, Tibetans, like North and South American high-altitude residents, have larger lung volumes. This may be important for raising lung diffusing capacity and preserving arterial oxygen saturation during exercise. PMID- 1746643 TI - Characteristics of hamadryas-like male baboons living in anubis baboon troops in the Awash hybrid zone, Ethiopia. AB - In the twenty-two years since the Awash baboon hybrid zone was first described, about 25-30 hamadryas or hamadryas-like hybrid males have taken up residence in anubis baboon groups. Most enter as mature adults, though some may immigrate as juvenile followers. Long-term tracking of known immigrants indicates that they may reside for four years or more in their adopted troop, during which time they establish a series of comparatively short-term harems, and probably sire hybrid offspring. "Abductions" of anubis females to hamadryas troops, as postulated by early observers, were not seen, though their occurrence cannot be ruled out. Younger, more recent immigrants tend to be "purer" hamadryas in phenotype, perhaps reflecting a more distant origin, or a change in the composition of neighboring hamadryas populations. Coexisting hamadryas and anubis show no signs of reproductive isolation by behavioral barriers, and evidently belong to a single "recognition species." PMID- 1746644 TI - Interspecific perspective on mechanical and nonmechanical models of primate circumorbital morphology. AB - Linear dimensions and angular orientations of the browridge, postorbital bar, and postorbital septum were obtained from a representative series of primates and compared with variables associated with several nonmechanical and biomechanical/mechanical models put forward to explain the form and function of the circumorbital region. Analyses of the results indicate that face size is the primary determinant of variation in primate circumorbital morphology. Anteroposterior browridge thickness is correlated with neural-orbital disjunction among anthropoid primates, but not among prosimians. This difference appears related to differences in the construction of the upper face and anterior cranial fossa between prosimians and anthropoids. Little support is demonstrated for the anterior dental loading model of browridge development. Mediolateral postorbital bar width and (to a lesser degree) browridge height are correlated with neurofacial torsion during mastication and variation in masticatory muscle size. These analyses further suggest that since circumorbital structures (especially the browridges) are located the farthest away from the chewing apparatus, they are least affected by masticatory stresses. PMID- 1746645 TI - Articular and diaphyseal remodeling of the proximal femur with changes in body mass in adults. AB - Proximal femoral dimensions were measured from radiographs of 80 living subjects whose current body weight and body weight at initial skeletal maturity (18 years) could be ascertained. Results generally support the hypothesis that articular size does not change in response to changes in mechanical loading (body weight) in adults, while diaphyseal cross-sectional size does. This can be explained by considering the different bone remodeling constraints characteristic of largely trabecular bone regions (articulations) and largely compact cortical bone regions (diaphyses). The femoral neck shows a pattern apparently intermediate between the two, consistent with its structure. When the additional statistical "noise" created by an essentially static femoral head size is accounted for, the present study supports other studies that have demonstrated rather marked positive allometry in femoral articular and shaft cross-sectional dimensions to body mass among adult humans. Body weight prediction equations developed from these data give reasonable results for modern U.S. samples, with average percent prediction errors of about 10%-16% for individual weights and about 2% for sample mean weights using the shaft dimension equations. When predicting body weight from femoral head size in earlier human samples, a downward correction factor of about 10% is suggested to account for the increased adiposity of very recent U.S. adults. PMID- 1746646 TI - Euclidean distance matrix analysis: a coordinate-free approach for comparing biological shapes using landmark data. AB - For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form can be conveniently defined as consisting of size and shape. Several approaches for comparing biological shapes using landmark data are available. Lele (1991a) critically discusses these approaches and proposes a new method based on the Euclidean distance matrix representation of the form of an object. The purpose of this paper is to extend this new methodology to the comparison of groups of objects. We develop the statistical versions of various concepts introduced by Lele (1991a) and use them for developing statistical procedures for testing the hypothesis of shape difference between biological forms. We illustrate the use of this method by studying morphological differences between normal children and those affected with Crouzon and Apert syndromes and craniofacial sexual dimorphism in Cebus apella. PMID- 1746647 TI - Brief communication. on the problem of immunological detection of antigens in skeletal remains. AB - A detailed investigation with affinity-chromatography-purified fractions of antihemoglobin serum from rabbit shows that the hemoglobin content of human bones dating back 15 to 3,000 years may be very small. Some of the previous results (Ascenzi et al., 1985) indicating a high hemoglobin titer were +vitiated because of an unexpected cross-reactivity of bone extracts with the hemoglobin-unreactive fraction of the antiserum. PMID- 1746648 TI - Strategies to prevent HIV infection in the United States. PMID- 1746649 TI - Health for all: a public health vision. AB - The approach of a millennial passage invites public health to a review of past performance and a preview of future prospects toward assuring a healthy public. Since the 1974 Canadian Lalonde report, the best national plans for health progress have emphasized disease prevention and health promotion. WHO's multinational Health for All by the Year 2000 promotes basic health services essential to leading a socially and economically productive life. Healthy People 2000, the latest US guide, establishes three goals: increase healthy life span, reduce health disparities, and achieve universal access to preventive services. Its objectives can be used to excite public understanding, equip program development, evaluate progress, and encourage public accountability for health initiatives. Needed is federal leadership in defining requisite action and securing necessary resources. Elsewhere a "new public health" emphasizes community life-style and multisectoral "healthy public policy." In the United States, a national health program is needed to achieve equity in access to personal health care. Even more essential is equitable sharing in basic health determinants in society--nutritious food, basic education, safe water, decent housing, secure employment, adequate income, and peace. Vital to such a future is able and active leadership now from governments and public health professionals. PMID- 1746650 TI - Lessons from London: the British are reforming their national health service. AB - In an effort to keep abreast of the changing needs of a more affluent society and to ensure better value for money, the British are reforming their National Health Service. They are promoting competition and entrepreneurship, and directing funding to follow a patient rather than flowing directly to institutions. British physicians are resisting these changes. The United States, in the middle of a health care crisis of its own, can learn a great deal from Britain, especially in the area of controlling expenditures. The low cost of the National Health Service can be attributed to four major factors: (1) It is general practitioner driven and no patient accesses a specialist or hospital directly. (2) Hospitals, which employ all the specialists and supply most of the technology, operate on very tight, cash-limited budgets. (3) Administrative costs are very low. (4) The expense of malpractice is not (yet) a major concern. Changes occurring in both countries foretell a future wherein our health care systems may look very much alike. PMID- 1746651 TI - Injury-related medical care utilization in a problem drinking population. AB - BACKGROUND: Population-based data on the overall risk of injury among problem drinkers are extremely limited. METHODS: We conducted an eight-year study of injury-related medical care utilization for a group of problem drinkers (n = 3 729) enrolled in the health insurance plan of a large manufacturing firm with plants in a number of midwestern states. A comparison non-problem drinking cohort matched on age, gender, and number of years of enrollment with the same company plan was also utilized. RESULTS: Problem drinkers utilized injury-related medical care at a rate 1.6 times that of the comparison group and experienced injury related medical care costs which were three times as high. Increased risks were found for both men and women and for all ages studied. CONCLUSIONS: This study is one of the few to examine the overall incidence of fatal and non-fatal injuries among a large population of problem drinkers and provides evidence that higher medical care costs are associated with chronic alcohol use. PMID- 1746652 TI - HIV infection, genital ulcer disease, and crack cocaine use among patients attending a clinic for sexually transmitted diseases. AB - BACKGROUND: Recently there has been a rise in genital ulcer disease (GUD) in urban minority heterosexuals in the United States. The impact of these increased GUD rates on HIV transmission patterns in this population is unknown. METHODS: Sexually transmitted disease (STD) diagnoses were correlated with HIV antibody status and risk factor history in 194 patients who consented to HIV testing at an STD clinic in central Brooklyn. RESULTS: Of 36 HIV-positive patients, 23 (64%) denied HIV risk factors other than heterosexual contact with persons of unknown HIV status. HIV antibody was associated with GUD (odds radio [OR] = 2.72, 95% confidence interval [CI] = 1.20-6.24), multiple concurrent STDs (OR = 2.51, 95% CI = 1.08-5.81), and a history of crack cocaine use (OR = 2.98, 95% CI = inexact 9.61). Crack use was also associated with GUD (OR = 15.15, 95% CI = 3.27-inexact) and multiple simultaneous STDs (OR = 13.87, 95% CI = 4.62-inexact). In a log linear model analysis, HIV infection was independently associated with GUD and crack use. HIV infection, genital ulcer disease, and crack cocaine use were more common in women than men. CONCLUSIONS: The association between HIV infection and GUD seen here may be secondary to high-risk sexual behavior, which in turn may be partially attributable to crack cocaine use and drug-related prostitution. The high rate of coinfection with HIV and GUD raises a concern about the increased efficiency of sexual transmission of HIV in this population. PMID- 1746653 TI - Reduction of high-risk sexual behavior among heterosexuals undergoing HIV antibody testing: a randomized clinical trial. AB - BACKGROUND: We evaluated the effect of HIV antibody testing on sexual behavior and communication with sexual partners about AIDS risk among heterosexual adults at a clinic for sexually transmitted diseases. METHODS: We randomized 186 subjects to receive either AIDS education alone (the control group) or AIDS education, an HIV antibody test, and the test results (the intervention group). These subjects were then followed up 8 weeks later. RESULTS: At follow-up, mean number of sexual partners decreased, but not differently between groups. However, compared with controls, HIV antibody test intervention subjects, all of whom tested negative, questioned their most recent sexual partner more about HIV antibody status (P less than 0.01), worried more about getting AIDS (P less than 0.03), and tended to use a condom more often with their last sexual partner (P = 0.05): 40% of intervention subjects vs 20% of controls used condoms, avoided genital intercourse, or knew their last partner had a negative HIV antibody test (P less than 0.005). CONCLUSION: HIV antibody testing combined with AIDS education increases concern about HIV and, at least in the short term, may promote safer sexual behaviors. Additional strategies will be necessary if behaviors risky for HIV transmission are to be further reduced. PMID- 1746654 TI - Behavior changes after notification of HIV infection. AB - BACKGROUND: To learn more about how people who did not volunteer for testing react to information about HIV infection, we assessed short-term behavior changes in HIV-positive blood donors. METHODS: Blood donors who were notified at the New York Blood Center that they were HIV positive were asked to participate in a study. A nurse elicited a medical history, performed a limited medical examination, and asked participants to complete a questionnaire that included questions about drug use, sexual behavior, and psychological characteristics. Participants were asked to return in 2 weeks to complete another questionnaire. RESULTS: Many fewer men and women reported engaging in unsafe sexual behaviors in the 2 weeks preceding the follow-up visit than had reported such behaviors prior to notification. These changes were greater than those other investigators have reported, but about 40% of the participants still reported unsafe sexual activity at the follow-up interview. CONCLUSIONS: To make nonvolunteer screening programs for HIV infection more effective in reducing the spread of HIV infection, we need to learn more about how to help people change their high-risk behaviors. PMID- 1746655 TI - Knowledge about AIDS and HIV in the US adult population: influence of the local incidence of AIDS. AB - BACKGROUND: Accurate information about acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) is important for prevention. This study determined whether AIDS knowledge varied among populations residing in areas with a low, medium, or high incidence of AIDS. METHODS: Respondents to the 1988 National Health Interview Survey of AIDS Knowledge and Attitudes, which is based on a nationally representative sample of 29,659 adults, were rated on their knowledge about modes of HIV transmission, general knowledge about AIDS, and misperceptions about HIV transmission through casual contact. RESULTS: Persons 50 years of age or older, Blacks, Hispanics, and persons with less than a high school education had lower knowledge scores and higher misperception scores. Residents of the high-incidence area had more misperceptions than those who lived in the medium- or low-incidence areas. Sociodemographic determinants of scores were important factors overall and within each AIDS incidence area. CONCLUSIONS: These data suggest that the ability of educational messages to reach and be absorbed by individuals nationwide is less dependent on whether they live in an area with a high incidence of AIDS and more dependent on other demographic variables. New and continued efforts are needed to improve knowledge in older persons, minorities, and the less educated in all parts of the country. PMID- 1746656 TI - HIV instruction, HIV knowledge, and drug injection among high school students in the United States. AB - BACKGROUND: The prevalence of HIV-related behaviors and determinants of these behaviors among adolescents in the United States have not been well studied. METHODS: To determine the prevalence of HIV-related drug behaviors and to assess the effects of HIV-related school-based instruction and HIV knowledge on these behaviors, data were analyzed from a 39-item, self-administered questionnaire completed by a probability sample of all students in grades 9 through 12 in the United States. RESULTS: Usable responses were obtained from 8098 students. Of these, 2.7% (95% confidence interval [CI] = 2.3-3.2) and 1.7% (95% CI = 1.3-2.1) reported injecting illicit drugs ever and during the past year, respectively. Corresponding prevalences of needle sharing were 0.8% (95% CI = 0.5-1.1) and 0.5% (95% CI = 0.3-0.7). Regression analysis revealed that students with higher knowledge scores were less likely and males more likely to have ever injected drugs. HIV knowledge was similarly associated with other outcome measures of drug injection behavior. Although HIV instruction did not directly influence drug injection behavior independently of demographic characteristics, it was positively associated with HIV knowledge. CONCLUSIONS: While these results do not establish a causal relationship, they suggest that HIV knowledge and school-based instruction may play a role in maintaining low levels of drug-injection behavior among high school students. PMID- 1746657 TI - Needle sharing in The Netherlands: an ethnographic analysis. AB - BACKGROUND: Needle sharing has been reported to be the main cause of the rapid spread of the human immunodeficiency virus (HIV) among injecting drug users. Risk behaviors such as needle sharing are, however, the end result of complicated interaction patterns in drug user networks, which have their specific rules and rituals, and larger social structures and official drug policy. METHODS: To study these interaction patterns we examined the drug administration rituals of heroin addicts in Rotterdam, The Netherlands. Intensive ethnographic descriptions were collected by participant observation. RESULTS: In less than 10% of the observed self-injections unsafe syringes were used. In 68% of the self-injections new, sterile syringes were used. Needle sharing as a planned sequence was not observed. Sharing was determined primarily by the availability of syringes, experience with the injecting ritual, and drug craving. In all observed needle sharing events, subjects were aware of the risks involved and undertook efforts to clean the injection equipment. CONCLUSIONS: In contrast to psychological approaches aimed at reducing individual "risk behavior," these findings suggest that HIV prevention can be made more effective if active drug injectors are organized to help themselves and their peers prevent high-risk exchange situations. PMID- 1746658 TI - Socioeconomic status and electrolyte intake in black adults: the Pitt County Study. AB - BACKGROUND: Although the inverse association between socioeconomic status (SES) and blood pressure has often been observed, little is known about the relationship between SES and dietary risk factors for elevated blood pressure. Therefore, this study described the distribution of dietary intakes of sodium, potassium, and calcium and examined the association between electrolyte intake and SES among 1784 Black men and women aged 25 to 50 residing in eastern North Carolina. METHODS: Household interviews were conducted in 1988 to obtain information on psychosocial and dietary correlates of blood pressure. Electrolyte intake (mg/day) was assessed using a food frequency questionnaire adapted to reflect regional and ethnic food preferences. SES was categorized into three levels defined by the participant's educational level and occupation. RESULTS: After adjustment for age and energy intake, potassium and calcium intake increased with increasing SES for both sexes. Sodium intake was high for all groups and did not vary markedly with SES, but sodium to potassium and sodium to calcium ratios decreased with increasing SES. In addition, high SES individuals were more likely to believe that diet affects risk for disease and to report less salt use at the table and less current sodium consumption than in the past. CONCLUSION: These data indicate that nutritional beliefs as well as the consumption of electrolytes are associated with SES in Black adults. PMID- 1746659 TI - An evaluation of the impact of maternity care coordination on Medicaid birth outcomes in North Carolina. AB - BACKGROUND: Care coordination is an important component of the enhanced prenatal care services provided under the recent expansions of the Medicaid program. The effect of maternity care coordination services on birth outcomes in North Carolina was assessed by comparing women on Medicaid who did and did not receive these services. METHODS: Health program data files, including Medicaid claims paid for maternity care coordination, were linked to 1988 and 1989 live birth certificates. Simple comparisons of percentages and rates were supplemented by a logistic regression analysis. RESULTS: Among women on Medicaid who did not receive maternity care coordination services, the low birth weight rate was 21% higher, the very low birth weight rate was 62% higher, and the infant mortality rate was 23% higher than among women on Medicaid who did receive such services. It was estimated that, for each $1.00 spent on maternity care coordination, Medicaid saved $2.02 in medical costs for newborns up to 60 days of age. Among the women who did receive maternity care coordination, those receiving it for 3 or more months had better outcomes than those receiving it for less than 3 months. CONCLUSIONS: These results suggest that maternity care coordination can be effective in reducing low birth weight, infant mortality, and newborn medical care costs among babies born to women in poverty. PMID- 1746660 TI - The importance of assessing the fit of logistic regression models: a case study. AB - BACKGROUND: The logistic regression model is being used with increasing frequency in all areas of public health research. In the calendar year 1989, over 30% of the articles published in the American Journal of Public Health employed some form of logistic regression modeling. In spite of this increase, there has been no commensurate increase in the use of commonly available methods for assessing model adequacy. METHODS: We review the current status of the use of logistic regression modeling in the American Journal of Public Health. We present a brief overview of currently available and easily used methods for assessing the adequacy of a fitted logistic regression model. RESULTS: An example is used to demonstrate the methods as well as a few of the adverse consequences of failing to assess the fit of the model. One important adverse consequence illustrated in the example is the inclusion of variables in the model as a result of the influence of one subject. CONCLUSIONS: Failure to address model adequacy may lead to misleading or incorrect inferences. Recommendations are made for the use of methods for assessing model adequacy and for future editorial policy in regard to the review of articles using logistic regression. PMID- 1746661 TI - Overcoming denial and increasing the intention to use condoms through the induction of hypocrisy. AB - Feelings of hypocrisy were induced in college students to increase condom use. Hypocrisy was created by making subjects mindful of their past failure to use condoms and then having them persuade others about the importance of condoms for AIDS prevention. The induction of hypocrisy decreased denial and led to greater intent to improve condom use relative to the control conditions. The implications of these findings for AIDS prevention are discussed. PMID- 1746662 TI - Knowledge about HIV and behavioral risks of foreign-born Boston public school students. AB - In 1990, 3049 Boston public middle and high school students were surveyed anonymously in English, Spanish, Vietnamese, Chinese, French, or Haitian Creole. Significantly fewer immigrant students, 35% of those surveyed, knew the principal modes of human immunodeficiency virus transmission. Fewer immigrants reported having sexual intercourse (31% vs 53% of nonimmigrants), but among the sexually active only 38% always used condoms, and more immigrants reported intercourse with intravenous drug users (4% vs 1% of non-immigrants). AIDS education should be taught to immigrant students in their native languages. PMID- 1746663 TI - HIV infection and risk behaviors among intravenous drug users in low seroprevalence areas in the Midwest. AB - We studied behavioral factors that place intravenous drug users at risk for the acquisition and transmission of the human immunodeficiency virus (HIV) in a sample of 855 individuals not in drug treatment, living in central and southwestern Ohio. The HIV seropositivity rate for the sample was 1.5%. Three factors were significantly related to HIV infection: homeless shelter residence (odds ratio [OR] = 7.7, 95% confidence interval (CI) = 3.0-20.0), travel to northeastern HIV hyperendemic areas (OR = 5.2, 95% CI = 1.8-15.4), and recent male homosexual or bisexual behavior (OR = 11.2, 95% CI = 2.9-43.9). PMID- 1746664 TI - Frequency and thoroughness of STD/HIV risk assessment by physicians in a high risk metropolitan area. AB - The US Preventive Services Task Force recommends that all primary care physicians assess the sexually transmitted disease/human immunodeficiency virus (STD/HIV) risk of all adolescent and adult patients. To determine whether factors amenable to change through continuing medical education are associated with frequent and thorough STD/HIV risk assessment, a telephone survey of primary care physicians in the Washington, DC metropolitan area was conducted (n = 961). Thirty-seven percent of physicians reported regularly asking new adult patients about their sexual practices; 60% asked new adolescent patients. STD/HIV risk questioning was associated with physicians' confidence in their ability to help prevent HIV, comfort with discussing patients' sexual practices, and perception of a large STD/HIV problem in their practice. These findings suggest that continuing medical education should target improvement in physicians' sexual practice questioning skills. PMID- 1746665 TI - Changes in AIDS case reporting after hospital site visits. AB - In an effort to improve AIDS case reporting, site visits (meetings with hospital staff to encourage reporting) were made to all Philadelphia hospitals. Comparisons of hospitals visited during a 7-week period with hospitals not visited during that period indicated that the site visits were followed by a marked increase in case reports. No similar increase was observed at the comparison hospitals. The increased reporting was accompanied by an increased lag time from diagnosis to report, suggesting that the additional reports at visited hospitals were the result of the identification of previously missed cases rather than a speedup of reporting. Cases reported after the visits were more likely to have white-collar occupations or private medical insurance than were those reported before the visits. PMID- 1746666 TI - Patterns of breast and cervical cancer screening at three public health centers in an inner-city urban area. AB - In an effort to examine breast and cervical cancer screening patterns among poor African-American urban women, medical records were abstracted at three public health centers located in the inner city of Chicago. The proportions of eligible women at these three centers who received Pap smears, breast examinations, and mammograms were computed. These proportions were notably low and differed significantly among the three centers. Because the literature is now suggesting that an appropriate sequence best defines adequate screening, sequences of screenings were also determined and were found to be lacking. All of these screening histories fall far below the screening objectives set by the National Cancer Institute for the year 2000. This information suggests that interventions are needed that will help health centers serving poor women to deliver more frequent cancer screening. PMID- 1746667 TI - The impact of vitamin A supplementation on morbidity: a randomized community intervention trial. AB - A randomized community trial investigated the impact of vitamin A supplementation on symptoms of respiratory and enteric infections among Indonesian children aged 1 to 5 years. A sample of 450 villages had been randomized into 229 villages that received vitamin A distribution and 221 that were observed as controls. The prevalence rates of cough, fever, and diarrhea were reduced in the treatment villages compared with the control villages by 8%, 5%, and 11%, respectively, but the reduction was not statistically significant. These results indicate that vitamin A supplements did not produce a substantial reduction in these symptoms, in spite of a reported reduction in all-cause mortality. PMID- 1746669 TI - Hooray for health! A health education program for day-care home providers. PMID- 1746668 TI - Epidemiology and the law: courts and confidence intervals. AB - Beginning with the swine flu litigation of the early 1980s, epidemiological evidence has played an increasingly prominent role in helping the nation's courts deal with alleged causal connections between plaintiffs' diseases or other harm and exposure to specific noxious agents (such as asbestos, toxic waste, radiation, and pharmaceuticals). Judicial reliance on epidemiology has high lighted the contrast between the nature of scientific proof and of legal proof. Epidemiologists need to recognize and understand the growing involvement of their profession in complex tort litigation. PMID- 1746670 TI - Lazy eyes and public vision: health department focus on preschool vision testing. PMID- 1746671 TI - Study on PMS and caffeine consumption flawed. PMID- 1746672 TI - Outbreak of Coxsackievirus A16 hand, foot, and mouth disease in a child day-care center. PMID- 1746673 TI - Liquid scintillation versus gamma ray counting in Radon measurements with charcoal. PMID- 1746674 TI - Homicide trends in New York State, 1980 to 1988. PMID- 1746675 TI - Suicides at Niagara Falls. PMID- 1746676 TI - Let's not "blame the victim"--exercise does protect against heart disease. PMID- 1746677 TI - Differences in biological responses to cigarette smoking remain unexplained. PMID- 1746678 TI - Histologic classification of the combined nevus. Analysis of the variable expression of melanocytic nevi. AB - The designation combined nevus gives recognition to mixed cytologic patterns. In the common variant, plump, pigmented spindle cells form fascicles among nests of ordinary nevus cells. In other variants, one or several cellular components that share cytologic features with either a blue nevus or a Spitz nevus are represented. Ninety-five cases, 49% of which were of the common type, were studied. Grossly, most of the lesions were darkly pigmented papules or nodules. The clinical diagnosis in three-fourths of the cases was nevus, blue nevus, or melanoma. Fifteen percent had concomitant histologic features of melanocytic dysplasia, and most of these lesions were of the common type. For the common variant, the cytologic features, pattern of apparent infiltration, and variable representation of the features of a premalignant melanocytic dysplasia often mislead a pathologist in interpreting and predicting biologic potential. In combined nevi, the phenotypic diversity and genetic lability of melanocytic nevus cells is manifested. PMID- 1746679 TI - Diffuse laminar endocervical glandular hyperplasia. A benign lesion often confused with adenoma malignum (minimal deviation adenocarcinoma). AB - We report seven examples of a hitherto undescribed pseudoneoplastic glandular lesion of the uterine cervix that we have designated "diffuse laminar endocervical glandular hyperplasia." The patients ranged in age from 22 to 48 (mean 37) years. Only one of them had a history of hormone intake. All the lesions were incidental findings in hysterectomy specimens performed for dysfunctional uterine bleeding (five cases) or symptomatic leiomyomas (two cases). Microscopic examination revealed a proliferation of moderate-sized, evenly spaced, differentiated endocervical glands within the inner one-third of the cervical wall, sharply demarcated from the underlying cervical stroma. Reactive atypia was seen in some cases but significant cytologic atypia was absent. A marked inflammatory response was present in five of the seven cases. The main consideration in differential diagnosis was adenoma malignum (minimal deviation adenocarcinoma). Major features that helped in this distinction were a lack of irregular stromal infiltration and a desmoplastic stromal response, and an absence of focal malignant cytologic features. Follow-up for an average of 6.5 years in five of the seven cases was uneventful. PMID- 1746680 TI - Sinusoidal hemangioma. A distinctive benign vascular neoplasm within the group of cavernous hemangiomas. AB - Twelve cases of sinusoidal hemangioma, a distinctive subset of the group of lesions known as cavernous hemangioma, are described. All presented as solitary subcutaneous/deep dermal lesions in adults, predominantly females. Five arose on a limb and five on the trunk; two of the latter were situated in mammary subcutaneous tissue. Histologically they were characterized by dilated, interconnecting, thin-walled vascular channels that frequently showed a pseudopapillary pattern. These vessels had a predominantly lobular architecture but peripherally showed focally ill-defined spread into subcutaneous tissue. The lining endothelium was single-layered but showed focal pleomorphism and hyperchromasia, which, combined with the pseudopapillae and apparent infiltrative pattern in areas, raised the possibility of angiosarcoma in four cases, most notably in the breast lesions. This possibility was further suggested by the presence of pseudonecrotic central infarction in two cases. Follow-up in eight cases, however, has revealed no tendency for either local recurrence or metastasis. PMID- 1746681 TI - Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). AB - Twenty-six cases of malignant peripheral nerve sheath tumor with a predominant epithelioid pattern were studied to determine the range of its histologic patterns, immunophenotype, and biologic behavior. The tumor presented as an asymptomatic mass either in superficial (16 cases) or in deep soft tissue (10 cases) of the extremity. Characteristically, those in deep soft tissue were composed of vague nodules of varying cellularity made up of cords or strands of rounded epithelioid cells with prominent nucleoli. Those in superficial soft tissue were uninodular masses composed of tight clusters of cells showing cell-to cell molding but possessing the same prominence of nuclei and mitotic activity as those in deep soft tissue. Several were associated with a preexisting benign nerve sheath tumor. A number of cases deviated from the above description, including cases that resembled a clear cell carcinoma, a malignant rhabdoid tumor, and a pleomorphic sarcoma. The majority of cases (80%) strongly expressed S-100 protein and neuron-specific enolase, but all lacked a melanoma-associated antigen (as defined by HMB-45) and cytokeratin. Stains for type IV collagen defined linear immunoreactivity around single cells and groups of cells. This pattern did not differ substantially from that of melanomas and therefore did not serve as a reliable discriminant. Follow-up information indicated a more favorable course for those in superficial soft tissue compared with those in deep sites. Two of 16 patients in the former group developed metastatic disease compared with three of 10 in the latter group. Tumors in superficial soft tissue may be eminently treatable and curable, depending on size. PMID- 1746682 TI - Inflammatory fibrosarcoma of the mesentery and retroperitoneum. A tumor closely simulating inflammatory pseudotumor. AB - We report 38 cases of inflammatory fibrosarcoma occurring in 23 females and 15 males, 2 months to 74 years of age (median, 8.5 years; mean, 15 years) with symptoms of abdominal pain (17 cases), anemia (21 cases), fever (14 cases), mass (16 cases), and gastrointestinal obstruction (7 cases). Primary tumor sites included mesentery and retroperitoneum (31 cases), omentum (two cases), mediastinum (two cases), liver (one case), diaphragm (one case), and abdominal wall (one case). Sizes ranged from 2.4 cm to 20 cm (mean, 9.6 cm). Follow-up data in 27 cases revealed local recurrences in 10 patients, with multiple local recurrences in three and histologically proven distant metastases to lung (two cases) and brain (one case). Five patients died from their disease (median, 20 months). All tumors, including metastases, consisted of fibroblasts, myofibroblasts, and plasma cells, with variable degrees of fibrosis and calcification. Immunostains indicate myofibroblastic differentiation; 18 of 20 (90%) stained for actin, 15 of 18 (83%) for vimentin, and 10 of 13 (77%) for keratin (primarily in a submesothelial location). Ultrastructural studies also disclosed myofibroblastic features. The locally aggressive, recurrent nature of these neoplasms, as well as the occurrence of metastases and tumor deaths, indicate that they are potentially malignant neoplasms that we believe are better classified as inflammatory fibrosarcomas, not as cellular inflammatory pseudotumors. PMID- 1746683 TI - Histologic grade, DNA ploidy, and intraglandular tumor extent as indicators of tumor progression of clinical stage B prostatic carcinoma. A direct comparison. AB - Histologic grade, DNA ploidy, and percentage tumor area were assessed in prostatectomy specimens from 73 patients with clinical stage B adenocarcinoma of the prostate and analyzed for their value as predictors of tumor progression. Further, the relationship between percentage tumor area and DNA ploidy was studied. Percentage tumor area was the indicator most strongly associated with the likelihood of tumor extension beyond the capsule of the prostate and of tumor progression as assessed in a logistic regression model. Grade was slightly superior to percentage area in predicting time to progression in a Cox model analysis. Increasing percentage tumor area was associated with an increased likelihood of aneuploidy. Little additional predictive ability was obtained with the concurrent use of two indicators in multivariate analysis, suggesting a high degree of interrelatedness of percentage tumor area, histologic grade, and DNA ploidy. DNA ploidy was not an independent predictive factor, and from a practical standpoint histologic grade and percentage tumor area were more important predictors of tumor progression than DNA ploidy. PMID- 1746684 TI - Assessment of ampulla of Vater pathology. An endoscopic approach. AB - One hundred eighty-nine endoscopic biopsies of the papilla of Vater were obtained from 125 patients during a 10-year period. Chronic inflammation was the most common histologic change identified. Of the 44 patients with papillary neoplasia, 42 were diagnosed by endoscopic biopsy. Sixteen of the 18 patients with invasive carcinoma were diagnosed by biopsy. Follow-up biopsies in patients endoscopically managed demonstrated recurrent tumors in 6 of 11 patients. With advances in instrumentation and techniques, pathologists can expect to see increasing numbers of ampullary biopsies. When multiple biopsy fragments are obtained and step sectioned, the diagnostic reliability of endoscopic biopsies in patients with tumors and carcinoma is greater than 90%. The morphologic spectrum of papillary lesions is similar to that seen in the colon with some significant exceptions. Tumor morphology varied considerably from area to area. Variations were seen in the basic architecture (villous-tubular), grade of dysplasia, presence of malignancy, and invasion from fragment to fragment, and in some cases from microscopic field to field. Another notable difference between the ampulla and colon is the rich mucosal lymphatic network of the ampullary region. Thus, any carcinoma invading the lamina propria was diagnosed as invasive carcinoma. PMID- 1746685 TI - Pleomorphic fibroma of tendon sheath. AB - We report an example of fibroma of tendon sheath with pleomorphic bizarre cells without mitoses. The tumor appears to be morphologically identical to a similar tumor in the skin and represents yet another example of a benign soft-tissue neoplasm with disturbing morphological features. PMID- 1746686 TI - Sarcomatoid neoplasm of monocytic lineage. PMID- 1746687 TI - [Features of the endometrial steroid receptor system in habitual abortion with high risk of infectious complications]. AB - Analysis of microbiologic and histologic findings and measurements of estrogen and gestagen receptors in the endometrium have shown manifest shifts in the endometrial steroid receptor system in women with asymptomatic chronic endometritis. The authors claim that disordered reception of steroid hormones may be regarded as one of the causes of spontaneous, abortions. PMID- 1746688 TI - [Several aspects of management of women with abortions in a women's clinic]. AB - Comprehensive instrumental examinations including hysteroscopy, tonometry, ultrasonic scanning were carried out in 190 women with symptoms of threatened abortion in pregnancy terms of 13-14 to 36-37 weeks. The findings evidenced that the presence of subjective signs of threatened abortion was not always supported by the results of objective instrumental examinations. Therapy of threatened abortions with commonly used drugs was monitored by instrumental methods; electro relaxation (non-medicinal physiotherapeutic method for correction of the uterine contractility) was carried out in 117 cases at the maternity center. The detection in these women of preclinical signs of threatened abortions permitted an early start of adequate therapy and was conducive to a reduction of the incidence of preterm deliveries. PMID- 1746689 TI - [Systemic lupus erythematosus and pregnancy: specific features of gestation and course of the disease]. AB - The authors analyze the course and outcomes of 33 pregnancies in 26 women suffering from systemic lupus erythematosus (SLE). In patients with active SLE the incidence of gestoses and abnormalities of the newborns is significantly higher than in those with inactive SLE, whose gestational and neonatal complication rate is almost the same as in healthy women. Pregnancy course and outcomes are particularly unfavorable in cases with lupus glomerulonephritis. PMID- 1746690 TI - [Homeostasis disorders in chronic hypoxia in pregnant women with heart defects]. AB - Central hemodynamics, free-radical lipid oxidation, anti-oxidant system, activities of lysosomal enzymes, and homeostasis system were studied in 86 pregnant women with congenital and acquired heart diseases. The studies have revealed a hypodynamic circulation type, activated lipid peroxidation processes, reduced level of alpha-tocopherol, a natural antioxidant, and activated coagulating and depressed anticoagulating system of the blood. These pathologic processes results in development of a mixed form of chronic hypoxia, augmenting with the progress of the heart condition. Assessment of these parameters helps timely start differentiated intensive care and improve labor outcome for the mother and fetus. PMID- 1746691 TI - [Functional state of the hepatobiliary system and immune status of pregnant women who have had viral hepatitis]. AB - Hepatobiliary function and immune status were evaluated in 92 pregnant women who had had viral hepatitis A (group 1) and in 35 who had suffered from viral hepatitis B. A control group included 102 healthy pregnant women. In group 1 there appeared clinical symptoms suggesting impairment of hepatobiliary system. It is suggested that pregnant women with the history of hepatitis should consult specialist on infections or gastroenterologist to specify the pathological process in order to correct it adequately. PMID- 1746692 TI - [Age-related features and possibilities of prognostication of the development of the reproductive system in girls living in the Amur Region]. AB - Physical and genital status of 2473 girls aged 12-16 was studied and factors of risk of development of the reproductive system in puberty detected. A scale for individual prediction of the reproductive function development, based on the girls' health status, body mass, exercise, was derived. PMID- 1746693 TI - [Pregnancy and labor in minor girls in the Ukraine]. AB - Analysis of the data on pregnancy and labor in girls under age in the Ukraine has shown a growing incidence of abortions, including criminal ones, in this population. Since these women come to consult a doctor too late, no necessary prophylactic measures can be taken, this being particularly hazardous in cases with extragenital diseases. Abortions in the third pregnancy trimester can be allowed only by vital indications after a consultation of several physicians. The author emphasizes the necessity of health-educating work at schools and vocational schools, as well as with parents, and of developing methods to prevent unplanned pregnancy. PMID- 1746694 TI - [Biological properties of peritoneal fluid in health and in pathology of the reproductive system]. PMID- 1746695 TI - [Features of the course of pregnancy and labor in students of higher education schools]. AB - Analysis of the course of pregnancy and labor in 50 students has revealed that half of these women suffered from gestoses and threatened abortions and more than half of them developed labor complications. These values were significantly lower in the reference group of age-matched women. PMID- 1746696 TI - [Coagulation parameters characterizing features of physiological course of pregnancy in primiparas and multiparas]. PMID- 1746697 TI - [Relations of the functional state of the visual analyzer and abnormalities of uterine contraction]. PMID- 1746698 TI - [Diagnosis of disorders of the fetal status using computer-assisted cardiotocography]. AB - The diagnostic system of cardiotocogram analysis in real time scale is described, and the diagnostic data of computer cardiotocography in various periods of os dilatation presented. Analysis of correlations and regressions of the parameters reflecting disorders of the fetal status has shown that the most significant parameter in the diagnosis of fetal status abnormalities is variability from beat to beat. PMID- 1746699 TI - [Effects of prenatal factors on the colloid-osmotic status of the newborn]. AB - Studies of prenatal factor effects on the newborns' colloid-osmotic status, a pressing problem in present-day obstetrics, were carried out in 2 groups of women: Group 1 consisted of 50 women with spontaneous delivery and Group 2, also consisting of 50 women, who delivered via cesarean section, 25 of them because of a cicatrix on the uterus and the rest because of severe gestoses characterized by nephropathy and Stage III pre-eclampsia. Blood samples were collected directly after delivery from the mother's vein and from the newborn's umbilical vein, and the colloid-osmotic status of the plasma was analyzed. The results permitted singling out a number of prenatal factors influencing the newborns' colloid osmotic status. These factors are as follows: obstetrical abnormalities, gestosis among other things; intensive care of the mother during delivery or after surgery, administration of diuretics, delivery mode, etc. These results have brought the authors to a conclusion that standardized infusion therapy without due consideration for the colloid-osmotic status is inadmissible, for it may result in iatrogenic complications in the newborns. PMID- 1746700 TI - [Clinical-morphological aspects of suppurative inflammatory diseases of the adnexa uteri]. AB - Draining of pyo-inflammatory foci of the uterine tubes, monitored by transvaginal echography, computer-aided tomography and laparoscopy, or surgery were carried out in 169 patients. Morphologic analysis helped define the characteristic features of the most prevalent clinical forms of pyo-inflammatory conditions of the uterine appendages and thus promoted a more accurate diagnosis of such conditions and their differentiated therapy. Immediate and late results of therapeutic draining of the pyo-inflammatory foci in the uterine tubes, monitored by the afore-said methods, are analyzed. PMID- 1746701 TI - [Hypothalamo-hypophyseal-thyroid system in patients with dysfunctional uterine bleeding]. PMID- 1746702 TI - [Pulsed secretion of gonadotropins in polycystic ovary syndrome]. AB - Pulsed secretion of gonadotropins was studied in 8 women suffering from polycystic ovarian syndrome, aged 23-28. Data on the time course of LH and FSH levels were processes by Santen and Bardin's method and by harmonic analysis. The results evidence that regular ejections of LH at a frequency higher than circahoralian rhythm (about 2 impulses per h) in such patients may be the cause of the development of the polycystic ovarian syndrome. Therapy with norcolut, carried out for 3 months, resulted in development of a trend to normalization of LH secretion, FSH secretion remaining unchanged. PMID- 1746703 TI - [Clinical course of the disease in familial and non-familial forms of serous cystadenocarcinoma of the ovary]. AB - A retrospective analysis of the case histories of patients with familial and nonfamilial ovarian carcinomas has shown that patients with the familial condition develop a higher resistance of the body to tumor dissemination and their survival rate is better. This conclusion may be of interest for those who research carcinogenesis mechanisms. PMID- 1746704 TI - [Biologically active agents associated with the placenta]. PMID- 1746705 TI - [Significance of tumor-associated CA-125 antigen in the diagnosis and monitoring of ovarian cancer]. AB - Blood serum levels of CA 125 were measured by enzyme immunoassay in 60 patients with ovarian carcinoma during the diagnosis and treatment of the condition. The level of this antigen was found correlating with the disease stage and surpassing the normal value in 18% of cases with Stage II, in 62.2% of those with Stage III, and in 91% of those with Stage IV condition. Therefore, measurements of CA 125 may be used in the diagnosis of ovarian carcinoma, identification of the origin of ascitic fluid, and objective evaluation of the therapeutic effect. CA 125 is a IVth Stage marker in cancer of the stomach or rectum. Measurements of this antigen improve the accuracy of ovarian carcinoma diagnosis by 15%. PMID- 1746706 TI - [Experimental and clinical studies of the causes of the rise of blood pressure during pregnancy]. PMID- 1746707 TI - [Modification of the ovary demedullation method in sclerocystic ovary syndrome]. PMID- 1746708 TI - [Early invasive cancer of the endometrium]. PMID- 1746709 TI - [Obstetrical tactics in patients who had undergone heart surgery]. PMID- 1746710 TI - [Use of polymer materials in surgical gynecology]. PMID- 1746711 TI - [The effect of acid-base management on the oxygen uptake of the human body during hypothermic extracorporeal circulation]. AB - The effects of two different systems of acid-base management on whole-body oxygen consumption during and following hypothermic cardiopulmonary bypass were investigated in 42 patients undergoing coronary artery bypass grafting or valve replacement surgery. In group I (22 patients) pH-stat management and in group II (20 patients) alpha-stat management was used. METHODS. Anesthesia was performed with fentanyl, midazolam, and pancuronium bromide. Halothane was added whenever MAP exceeded 100 mmHg. Cardiopulmonary bypass was conducted with a membrane oxygenator and a roller pump. Pump flow varied between 2 and 2.5 l/min per m2 body surface area. Once patients had been initially cooled down to a venous blood temperature of 27 degrees C they were kept stable between 28 degrees C and 30 degrees C during the ischemic phase. Measurements were performed after sternotomy during normothermia (control values) and every 15 min from the start until termination of bypass. RESULTS AND DISCUSSION. Neither hemodynamic parameters (MAP, CI, SVR) nor rectal or skin temperatures differed significantly between the two groups during the entire study period. Although at 27 degrees C oxygen availability fell by 43% and 35% in groups I and II, respectively, mixed venous oxygen saturation was significantly elevated compared with the control value, because of a decrease of 60% and 51%, respectively, in the arterio-venous oxygen content difference and of 62% and 55%, respectively, in oxygen consumption. Rewarming led to normalization of the metabolic parameters except for oxygen availability, which was still decreased as a result of low hemoglobin content. After termination of the bypass oxygen consumption increased steadily, which may have been due either to the beginning of shivering or to repayment of an oxygen debt caused by hypothermic bypass. As statistically significant differences were detected between the two groups in metabolic parameters during the course of the investigation, the hypothesis of Rahn and Reeves [2, 3], according to which oxygen consumption must be expected to be higher with alpha-stat than with pH stat management, could not be verified by this study. PMID- 1746712 TI - [The combination of general anesthesia and interscalene block in shoulder surgery]. AB - Surgery on the shoulder often causes severe pain and, therefore, requires high doses of opiates. As postoperative pain is frequently treated inadequately, it is desirable to seek alternatives for providing effective analgesia. In a prospective study we examined the efficacy of balanced anesthesia consisting of general anesthesia combined with interscalene brachial plexus blockade for intra- and postoperative analgesia for operations on the shoulder. METHODS. Using the technique described by Winnie, interscalene block (ISB) was performed in 100 awake patients. After location of the brachial plexus by means of a peripheral nerve stimulator, we injected 40 ml bupivacaine 0.375%, after which general anesthesia (GA) was induced. At three predetermined points in time (recovery room, 8 h, and 24 h after the end of surgery), pain was evaluated by a visual analogue scale ranging from 0 to 10 and the extent of sensory blockade was tested by the pinprick method. The results of the pain scores and individual demands for analgesics were compared with a group of 22 patients who received only GA. Both groups were comparable in age, sex, and type of surgical procedure. RESULTS. We noted technical failure of the ISB in 8% of our patients. Side effects such as Horner's syndrome (18%), phrenic nerve paralysis (10%), and recurrent laryngeal nerve block (1%) were only temporarily observed during the action of the local anesthetics. During the surgical procedure, the group with ISB received a mean dose of 0.13 +/- 0.07 mg fentanyl versus 0.29 +/- 0.08 mg in the GA group (P less than 0.01) with equipotent doses of volatile anesthetics (1.0 to 1.5 MAC enflurane). Postoperative pain occurred for the first time in 39% of the patients given ISB later than 12 h after the end of surgery (average 8.7 +/- 5.9 h). In contrast, 95% of the patients with GA complained of pain in the recovery room. Pain measurement by the analogue scale clearly demonstrated the advantages of balanced anesthesia directly and 8 h after the operation (P less than 0.01). Even 24 h after the end of the surgical procedure the patients had better pain relief (P less than 0.05) in spite of the decreasing effect of the ISB. These significant differences led to the following results for postoperative treatment: 35% of the patients with ISB did not require additional analgesics during the first 24-h period after surgery, whereas 95% of those with GA requested analgesia. Only 32% of the ISB patients required opioids versus 86% with GA. The average duration of stay in the recovery room was reduced by 25% in the group with ISB (86 vs 134 min). In a final assessment, 84% of the patients were satisfied with the balanced anesthesia and only 5% were disappointed with the method. CONCLUSION. The combination of ISB and GA allows a reduction in intraoperative doses of opiates and facilitates postoperative pain management. Because of the low incidence of side effects, the lack of complications, and the high degree of patient acceptance, we recommend this type of balanced anesthesia for patients undergoing shoulder surgery. PMID- 1746713 TI - [The potentialities of EEG analysis using the Lifescan in anesthesiology]. AB - In 87 patients a new computerized EEG monitor was used in clinical anesthesia. Following aperiodic analysis, the Lifescan shows the computerized EEG in a striking color visualization allowing recognition of changes in the course of the EEG and of interhemispheric differences. The computerized EEG can be read after a brief training period. The changes caused by different clinical situations are visualized in detail. Different changes were observed with the anesthetics used. During induction with thiopentone a sudden increase in activity was obvious. During a lighter level of anesthesia with thiopentone beta activity was easily recognizable. During induction with high-dose fentanyl frequency was slowed over a long period and activity was increased. The monitor shows the changes in the lower frequency range in detail. A bimodal pattern occurred with a higher dosage of enflurane. During lightening of anesthesia with enflurane a typical pattern indicated return to consciousness. When nitrous oxide was administered during anesthesia with halothane, and to a lesser degree during anesthesia with enflurane or isoflurane, remarkable slowing and decrease in activity occurred. The monitor allowed detailed recognition of the different patterns obtained with the various anesthetics. In some cases it was possible to say what dosage of the anesthetic used had been given or what depth of anesthesia had been achieved. The effect of combined anesthesia, however, was difficult to judge. In carotid artery surgery a quick unilateral decrease in activity and slowing of frequency indicated cerebral ischemia and quickly disappeared after insertion of a shunt. This change was particularly obvious with the new monitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746714 TI - [Comments on the article by D. Jooss et al. Bronchial rupture. Diagnosis and therapy of a rare complication of the use of a double-lumen tube]. PMID- 1746715 TI - Fine structure of the human synovial lining cell in osteoarthritis: its prominent cytoskeleton. AB - The cytoskeleton of the human osteoarthritic synovial lining cell (SLC) consists of an extensive number of vimentin intermediate filaments (IFs) in addition to microfilaments and microtubules. The IFs are especially prevalent in the SLC processes, but are commonly seen in a paranuclear arrangement. Processes, ending in numerous microvilli and blebs, project into the joint space. Scanning electron microscopy (SEM) further reveals the processes that may parallel the synovium surface for a short distance. IFs extend to the termination of such Numerous pinocytotic vesicles and extensive rough endoplasmic reticulum (rER) are characteristic of the type B cells. Lysosomes and long microvilli identify the type A cell. Punctate adherens, gap junctions, and cilia are the cell membrane specializations of the osteoarthritis (OA) synovium. A comparison with synovium from rheumatoid arthritis (RA) patients is made in order to assess the effect o this inflammatory disease on the SLC cytoskeleton, cell type relationship, and cell arrangement. The prominent cytoskeleton appears to play an important role in the architecture of the synovium. Our findings are further presented in the form of a drawing which in some aspects could describe the morphology of the normal synovium. PMID- 1746716 TI - Formation and release of vesicles from the basal surfaces of rat eye non pigmented ciliary epithelial cells: a novel secretory mechanism? AB - When rat ciliary body is processed by high pressure freezing and freeze substitution, numerous membrane-bound vesicle profiles are seen in the vitreous associated with the pars plana and in the valleys between the ciliary processes. They consist of a homogeneously distributed fine granular matrix and varying numbers of ribosome-like structures. The mechanism by which these vesicles are secreted appears to follow an apocrine-type pattern, albeit at the basal cell surface. Matrix material accumulates between the basal plasma membrane of non pigmented ciliary epithelial cells and a cortical layer of cytoskeletal components; the blebs thus formed protrude through a discontinuity in the basal lamina and, by a progressive narrowing of the neck region, are eventually pinched off, giving rise to free vesicles. Under conventional aqueous chemical fixation conditions, most of these vesicles are washed away or their contents solubilized and extracted, which accounts for their not having been identified hitherto as genuine morphological structures. They are nonetheless apparent, albeit in reduced numbers and mostly empty. Such vesicles are also observed in tissue processed according to several other chemical fixation techniques, namely, conventional fixation in the presence of the cationic dye ruthenium hexamine trichloride, simultaneous glutaraldehyde/osmium tetroxide fixation, and microwave fixation. In the latter instance, comparable vesicle preservation to that obtained by high pressure freezing/freeze substitution may be achieved if fixation is followed by cryoprotection, plunge freezing, and freeze substitution instead of conventional post-fixation and dehydration procedures. PMID- 1746717 TI - Cell and matrix biology of the suprapatella in the rat: a structural and immunocytochemical study of fibrocartilage in a tendon subject to compression. AB - The structure, ultrastructure, histochemistry, and immunohistochemistry of the suprapatella have been described in the rat. The suprapatella is a fibrocartilaginous sesamoid within the tendon of quadriceps femoris that articulates with the femoral condyles during flexion of the knee joint and reduces the amount of bending required at the tendon-bone junction. The cells of the suprapatella were much larger and more numerous than those in the associated tendon and were packed with vimentin-containing, intermediate filaments. The tendon cells contained far fewer filaments. The cells of both regions contained actin and tubulin. Histochemical and immunohistochemical studies showed that the suprapatellar cells were embedded in a matrix that is rich in chondroitin sulphate, but does not contain keratan or heparan sulphate. The fibrocartilage of the adjacent attachment zone of the quadriceps tendon also contained chondroitin sulphate, but in addition was rich in type II collagen. The structure of the suprapatella was similar to that of the fibrocartilaginous regions of tendons that pass around bony pulleys. However, there were differences in matrix composition that could reflect functional differences between the fibrocartilages. PMID- 1746718 TI - The anionic charge barrier in the renal corpuscle of the pronephros in the lamprey, Petromyzon marinus L. AB - The charge barrier within the renal corpuscle of the pronephric kidney of the lamprey, Petromyzon marinus, was investigated at two life cycle intervals using cationized ferritin and polyethyleneimine. In the larval renal corpuscle the endothelium of the glomerular capillaries and the laminae rarae externa and interna of the glomerular basement membrane show regularly-spaced deposits of the tracers. The lamina densa remains unstained. Concomitant with a loss of major processes of the visceral epithelial podocytes and development of an extensive mesangial matrix in late adult life are alterations in the distribution of the anionic sites. The lamina rara interna is no longer a distinct entity and the mesangium contains irregularly-distributed anionic sites surrounding electron dense deposits. The results indicate that the distribution of the anionic sites during adult life most likely affects the ability of the renal corpuscle to act as an efficient filtration device. This charge distribution is consistent with that seen during some renal pathologies of higher vertebrates. PMID- 1746719 TI - Interactions between rat epididymal epithelium and spermatozoa. AB - We studied in the rat epididymis the presence of membrane-bounded vesicles in the stereociliar areas of the epithelial cells. The intimate contact between principal cell stereocilia and luminal spermatozoa was also explored. The epididymidis of adult male albino rats were fixed with Mollenhauer's fixative via the thoracic aorta; they were removed and the caput and the cauda were separated and fixed for 4 additional hours at 4 degrees C. After fixation, the samples were processed with routine techniques for transmission and scanning electron microscopy. The study showed membrane-bounded vesicles in the lumen of the caput and cauda epididymidis. They are present between stereocilia, in the most peripheral regions of the epididymal lumen, and in a stereocilia-free zone in the apical plasma membrane of the principal cells. The smaller vesicles are located near the apical surface of the latter, and the larger ones are located near the tips of the stereocilia. Their contents are electron lucent in some images and electron dense in others. In several thin sections some of the vesicles are observed to have a stalk. This suggests that the possible mode of production may be an exocytotic process. Some membrane-bounded vesicles were found to be in contact with the head or the tail of maturating spermatozoa. Moreover, an intimate contact was found to exist in the epididymidis between the plasma membranes of the spermatozoa and the stereocilia. These observations seem to suggest two possible mechanisms for sperm-epididymal cell relations: 1) release of a secretion product via the membrane-bounded vesicles and 2) direct contact between stereocilia and spermatozoa. PMID- 1746720 TI - Morphometric study of the human neonatal ovary. AB - A morphometric analysis, based on mathematical evaluations and stereological methods, has been used to study five left neonatal ovaries, removed from full term neonates with a 46,XX karyotype free from malformations of the genital apparatus. Each ovary was completely cut obtaining serial sections and one 1 micron-thick section every 1,000 microns was examined. Ovarian length ranged from 9 to 17 mm (mean 13 mm), width from 3.5 to 7 mm (mean 5.7 mm), thickness from 2.5 to 5 mm (mean 4 mm), and volume from 82.23 to 198.3 mm3 (mean 125.88 mm3). In the ovarian cortex, primitive cortical tissue accounted for 10-20% of the total volume, follicles for 10-25% and interstitium for 35-45%; 10-30% of the organ consisted of inner medulla. The total follicle number ranged from 130,000 to 385,000 per ovary, with an average of 266,000 with 95% being represented by primordial follicles. In all ovaries examined follicular growth was still in process, with follicles at different stages of development. PMID- 1746721 TI - Application of stereological analysis of cell volume to isolated myocytes in culture with and without adrenergic innervation. AB - A three-dimensional analysis to evaluate structural changes in cultured cardiac myocytes following adrenergic innervation was performed using stereological techniques formerly limited to cells in tissue and organs. Cell volumes were calculated for two groups of cells at 96 hours in culture: isolated myocytes and myocytes innervated with adrenergic neurons. Relative and absolute volumes of the nucleus, cytoplasm, and cell were quantified by systematically sampling sections throughout the cell and by point count sampling techniques. Volumetric estimates were similarly determined for the mitochondria, sarcomeres, and other cellular components in the cytoplasm. Data were analyzed with ANOVA and randomized block design to control for variation among the cultures. Adrenergic innervation produced a 44% increase in cell volume, X +/- SEM, (3,344 +/- 196 microns3 to 4,816 +/- 400 microns3, P = 0.007). The absolute volume of mitochondria significantly increased after innervation (521 +/- 42 microns3 to 744 +/- 54 microns3, P less than 0.01). Absolute sarcomere volume did not change significantly (750 +/- 92 microns3 to 642 +/- 1061 microns3, P = 0.14). Other cellular components, defined as all cytoplasmic components except mitochondria and sarcomeres, significantly increased with innervation (1,739 +/- 166 microns3 to 3,097 +/- 338 microns3, P = 0.02). The relative volume of the nucleus and the cytoplasm in the cell remained unchanged following innervation. However, the relative volume of mitochondria decreased by 6%, the percent of the cytoplasm occupied by the sarcomeres decreased by 44%, and the volume occupied by the other cellular components increased by 22%. These findings support the use of stereological analysis as a means to quantify cell volumes of cultured myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746722 TI - Immunochemical localization of extracellular materials in bone marrow of rats. AB - The distribution of type I collagen, fibronectin, laminin, and heparan sulfate was studied in marrow of rats by indirect immunofluorescence. Most of the type I collagen of marrow is associated with large blood vessels and connective tissue trabeculae, but type I collagen was also localized in a delicate meshwork throughout the marrow and in the basement membrane of the sinusoidal endothelium. Fibronectin is partially co-distributed with type I collagen, but is much more widely distributed. Sheets or septa of fibronectin-rich material divide the marrow into small compartments that contain and appear to separate clusters of developing blood cells. These septa may serve as a substrate for anchorage and migration of blood cells. Labeling of laminin was observed in the basement membranes of blood vessels, of fat cells, and of the sinusoidal wall, but only scattered labeling was seen in other extracellular materials. Heparan sulfate proteoglycan was poorly labeled in the extracellular matrix of marrow. PMID- 1746723 TI - Organization of the membrane skeleton in spreading mouse blastomeres. I. Morphological analysis. AB - Differentiation in the mouse embryo begins at the 8-cell stage when the blastomeres spread against each other in a process called compaction. The spreading behavior of blastomeres on lectin-coated coverslips mimics that of blastomeres in the embryo, and we have utilized this model system to obtain an en face view of the membrane skeleton in the spreading blastomeres. Embryos were cultured on the coverslips for periods ranging from 20 sec to 6 hr, and the cells were disrupted to expose the cytoplasmic face of the adherent membranes and their associated filaments. The "membrane lawn" preparations were fixed, critical point dried, rotary shadowed, and the replicas examined by transmission electron microscopy. Using this technique we found that the plasmalemma of rounded blastomeres is associated with a lacy 3-dimensional filamentous meshwork that is transformed into a thin mat of densely woven filaments when the cells flatten. The overall organization of the membrane skeleton is similar in flattening 2- and 8-cell embryos, but there are significant differences in the time required for spreading to take place, in the means whereby the membrane skeletons are reorganized, and in the extent of maximal flattening. The significance of these observations for the compaction process is discussed. PMID- 1746724 TI - Changes in glycoconjugate expression during early chick embryo development: a lectin-binding study. AB - A selection of lectins was used to investigate developmentally regulated changes in the distribution of cell surface oligosaccharides during the gastrulation and neurulation stages of early chick embryo development. Lectins from three specificity classes were used: glucose/mannose specificity (concanavalin A [Con A], Lens culinaris agglutinin [LCA], Pisum sativum agglutinin [PSA]); N acetylglucosamine specificity (Lycopersicon esculentum agglutinin [LEA], wheat germ agglutinin [WGA], succinylated WGA [sWGA]); N-acetylgalactosamine/galactose specificity (Dolichos biflorus agglutinin [DBA], soybean agglutinin [SBA], Sophora japonica agglutinin [SJA], Bandeiraea (Griffonia) simplicifolia lectin I [BSL I], peanut agglutinin [PNA], Artocarpus integrifolia lectin [Jacalin], Ricinus communis agglutinin-1 [RCA-1], Erythrina cristagalli lectin [ECL]). At gastrulation stages, patterns of lectin binding could be distinguished in the epiblast, mesoderm, and endoderm cell layers. The primitive streak failed to bind any of the lectins, but LEA and WGA bound to the epiblast in regions lateral to the streak, indicating the loss of some glucosamine residues medially in preparation for the ingression movements of gastrulation. Several lectins showed marked binding to the mesoderm cells after their passage through the primitive streak; these were LCA, PSA, WGA, sWGA, BSL, and most particularly PNA. Therefore, the epithelial-mesenchymal transformation from epiblast to mesoderm at the primitive streak is accompanied by cell surface oligosaccharide changes in the epiblast and mesoderm that involve all classes of lectins including the PNA binding sequence Gal beta 1-3GalNAc. Ultrastructurally, PNA was shown to bind extracellularly to matrix fibrils. Jacalin, having the same sugar specificity as PNA, but binding to serine/threonine linked chains rather than asparagine linked chains showed no binding to the mesoderm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746725 TI - Talpid2 mutant chick limb has anteroposterior polarity and altered patterns of programmed cell death. AB - The talpid2(ta2) chick mutant is of interest for the study of limb pattern formation. Talpid2 is a simple Mendelian recessive lethal mutation which affects the mesoderm and results in short, spade-like, polydactylous wings and legs. Here, we describe ta2 limb development with particular attention to those aspects of ta2 which may illuminate the process of normal limb development. From the onset of budding, ta2 limb buds are significantly wider than normal buds along the anteroposterior axis. They lack the normal anterior and posterior necrotic zones and have variable development of the central opaque patch. Interdigital programmed cell death is variable and may result in development of distal phalanges without more proximal ones. Talpid2 wing vasculature is similar to that of normal wings; but ta2 legs are supplied by four large blood vessels. Feathers form regular, parallel rows, similar to normal feathers, but ta2 embryos lack the loose mesenchyme which separates the feather buds. Finally, and most significantly, ta2 wings and legs display anteroposterior polarity. Anterior and posterior limb skeletal elements can be clearly distinguished from one another within the ta2 phenotype. Our observations suggest that the ta2 mutant may be useful in analyzing programmed embryonic cell death and anteroposterior limb pattern formation. PMID- 1746726 TI - Sectional anatomy of the pelvis in the male rat with ultrasound correlations. AB - Ten-week-old male Wistar rats were used for sectional anatomy and ultrasonic diagnosis of the pelvis. The prostate and the urinary bladder were identified easily on longitudinal section by ultrasound examination. The prostate (ventral, lateral, and dorsal lobes) was located in the midline of the pelvis cavity on transverse sections and the caudal side of the urinary bladder on longitudinal sections. The urinary bladder was positioned at the cranial side of the prostate on longitudinal sections and in the midline of the pelvis cavity on transverse sections. The seminal vesicles were located at right and left positions of the urinary bladder. Ultrasonic diagnosis was estimated to be useful for experimental studies and we hope that ultrasound techniques may reduce the number of rats used for the treatment of prostate and urinary bladder cancers. PMID- 1746727 TI - Inflated, dried whole lung specimens. AB - A method is described for preparing fully-inflated whole lung specimens that are suitable for instruction or research purposes. Undamaged lungs are removed from the body and then tracheally cannulated and lavaged with tap water more than 250 times. The treatment also includes rinsing blood from vessels with water. A final filling of the lung with alcohol is optional. The multiply rinsed lung is drained and inflated to 30 cm of H2O pressure with dehumidified air and held at that pressure until the tissue is completely dry. The resulting specimens are light in color and appear to be permanent if stored properly. PMID- 1746728 TI - Magnetic resonance imaging in minor head injury. AB - STUDY OBJECTIVES: To investigate the role of cranial magnetic resonance (MR) imaging in evaluating patients discharged from the emergency department after minor head injury. DESIGN: A prospective blinded cohort study. SETTING: University hospital ED. TYPE OF PARTICIPANTS: Fifty-eight patients with minor head injury who were discharged from the ED with written head injury instructions. Patients admitted to the hospital were excluded. INTERVENTIONS: Ultra-low-field cranial MR scans were performed on patients within 24 hours of discharge. Scans were read blindly by two radiologists. MEASUREMENTS AND MAIN RESULTS: Fisher's exact test was used to compare symptoms in patients with abnormal and normal MR scans. There was no significant difference in symptoms between patients with abnormal and those with normal scans (P greater than .10). The proportion of abnormal MR scans was analyzed using the binomial distribution. Six of the 58 patients (10.3%) had traumatic intracranial abnormalities (proportion, 0.103; SD, 0.04; 95% CI, 0.04-0.21). Three had cortical contusions, and three had small subdural hematomas. Two of the six patients with abnormal MR scans, both with small subdural hematomas, had normal computed tomography scans. CONCLUSION: Ten percent of patients discharged from the ED after minor head injury had abnormal ultra-low-field cranial MR scans. Additional research is needed to establish the clinical importance of this unexpected observation. PMID- 1746729 TI - Is routine computed tomography scanning too expensive for mild head injury? AB - OBJECTIVE: To compare relative costs of treating mildly head-injured patients by routine admission or by using skull radiographs or cranial computed tomography (CT) scanning to screen patients for admission. DESIGN: Retrospective record review, hypothetical costs based on actual patient course and requirements. SETTING: Southern New Jersey Regional Trauma Center at Cooper Hospital/University Medical Center. PARTICIPANTS: 658 consecutive mildly head-injured patients admitted from 1986 to 1988. All were given cranial CT scans. MEASUREMENTS: Records were reviewed retrospectively and hypothetical costs were calculated based on actual length of hospitalization, surgical intervention, etc. These costs were compared for different treatment protocols. MAIN RESULTS: The average cost if every patient had been admitted for observation given skull radiographs, with CT scans done on those exhibiting skull fracture or later deterioration, was $1,207. If the CT scan had been used to identify patients with intracranial lesions and the others had been discharged, costs would have been almost 10% less. Had skull radiography been used to screen admissions, costs would have been 22% below those of routine CT scanning. However, these small savings are likely to be reduced by additional expenses related to missed intracranial lesions. CONCLUSIONS: Every patient with loss of consciousness or post-traumatic amnesia should have routine CT scanning. If the scan is normal and there are no other reasons for admission, the patients can be discharged safely from the emergency department. This represents optimal care from a medical standpoint and is justified from a cost-effectiveness point of view. PMID- 1746730 TI - Randomized, prospective comparison of open and closed peritoneal lavage for abdominal trauma. AB - STUDY OBJECTIVE: The study was designed to determine if open peritoneal lavage is superior to closed peritoneal lavage. DESIGN AND PARTICIPANTS: Patients who were admitted to a trauma center and needed peritoneal lavage were assigned to alternate trauma teams. Team 1 performed only open lavages one month and then switched to closed lavages; team 2 did only closed lavages and then switched to open lavages. MEASUREMENTS: The incidences of positive lavages and lavage complication were noted. Also measured were the length of time for catheter insertion, length of time of fluid retrieval, volume of effluent, technical difficulty of lavage, training level of the operator, effluent RBC count, and material cost. RESULTS: Two hundred twenty patients were randomized. No differences were noted in complication rate, volume of effluent, or length of time for fluid retrieval. Significant differences were noted for catheter insertion time (3.6 minutes for closed lavage and 6.9 minutes for open), ease of catheter insertion (closed technique is favored), and material cost ($96.26 for open lavage and $69.70 for closed lavage). CONCLUSION: Closed peritoneal lavage is superior to open peritoneal lavage in abdominal trauma; it is faster, easier to use, cheaper, and as safe as open lavage. PMID- 1746731 TI - The efficacy and safety of methohexital in the emergency department. AB - STUDY OBJECTIVE: To determine the efficacy and safety of methohexital sodium (MTX) in emergency department patients. DESIGN: A consecutive case series; all ED patients who received MTX from July 1989 through July 1990 were studied in a prospective manner. SETTING: A university hospital ED. PARTICIPANTS: All 102 adult and pediatric patients who received MTX. INTERVENTIONS: Emergency physicians trained in the use of MTX administered the drug. A study form was completed that provided data on dosage and response, indications for use, final diagnosis, hemodynamic and respiratory parameters, and an efficacy survey. RESULTS: Average cumulative dose of MTX was 1.6 +/- 1.3 mg/kg. The average duration of action per dose was 7.6 +/- 5.0 minutes. Leading indications for use were orthopedic procedures (54), endotracheal intubation (18), head computed tomography scan (ten), and wound care (eight). Hemodynamic changes were minimal; the average change in systolic blood pressure five minutes after MTX was -1.8 +/- 20 mm Hg. Average heart rate change was 3.0 +/- 20 beats. Percent respiratory depression was 17 +/- 24%. There was no correlation between MTX dose and the degree of respiratory depression. Narcotics and/or benzodiazepines were given with MTX in 92 cases, with no significant increase in respiratory depression. No major complications attributable to MTX were identified. CONCLUSION: MTX, when used by trained personnel who adhere to an established protocol, appears to be a safe and effective drug in selected ED patients. PMID- 1746732 TI - The impact of injury severity and prehospital procedures on scene time in victims of major trauma. AB - STUDY OBJECTIVE: To evaluate the relationship among injury severity, prehospital procedures, and time spent at the scene by paramedics for victims of major trauma. DESIGN: Retrospective study of 98 consecutive patients with an Injury Severity Score of more than 15 who were brought to a trauma center by fire department paramedics. SETTING: A medium-sized metropolitan emergency medical services (EMS) system and a Level I trauma center. RESULTS: There were 66 male and 32 female patients with a mean age of 34 years. Thirty-two patients (32.6%) died. Blunt and penetrating trauma accounted for 68.4% and 31.6% of cases, respectively. Thirty-three patients (33.7%) had successful advanced airway procedures, and 81 (82.7%) had at least one IV line started in the field. Analysis of scene time, prehospital procedures, and injury severity parameters revealed that more procedures were performed in the field on the more severely injured cases; that despite this, there was a trend toward shorter scene time for more severely injured patients; and that there was a mean scene time of 8.1 minutes. This is the shortest scene time reported to date for prehospital trauma care in an EMS system. CONCLUSION: Extremely short scene times can be attained without foregoing potentially life-saving advanced life support interventions in an urban EMS system with strong medical control. In such a system, the most severely injured victims may spend less time at the scene although more procedures are performed on them. PMID- 1746733 TI - Effect of standing orders on paramedic scene time for trauma patients. AB - STUDY OBJECTIVE: To determine if a protocol change that allowed paramedics to perform certain procedures before base station contact (standing orders) would decrease scene time in trauma patients. DESIGN: Retrospective review of case series. SETTING: A single-tiered, all advanced life support emergency medical services system. INTERVENTION: Implementation with standing orders for invasive procedures. TYPE OF PARTICIPANTS: All physiologically unstable trauma patients transported to a Level I trauma center by ambulance. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-seven patients met the inclusion criteria--87 before and 110 after the initiation of standing orders. Mean scene times for the control group (15.3 +/- 8.4 minutes) and for the standing orders group (15.1 +/- 7.6 minutes) were similar (P = .18). The power of the study to detect a two-minute difference in scene time was .92. Scene time was not influenced by mechanism of injury, and the number of procedures performed on patients was similar between the two groups. CONCLUSION: Standing orders did not decrease scene time in physiologically unstable trauma patients. Further study is necessary to delineate the factors that actually contribute to on-scene time and the factors that are important in determining whether standing orders or on-line medical contact should be used. PMID- 1746734 TI - Prospective study of manikin-only versus manikin and human subject endotracheal intubation training of paramedics. AB - STUDY OBJECTIVES: To determine the effect of manikin-only training on field success of endotracheal intubation by paramedics. DESIGN: Prospective evaluation of individual field endotracheal intubation success rates for paramedics after they participated in a manikin-only or a manikin-plus-cadaver training program. TYPES OF PARTICIPANTS: Paramedics responding to emergency calls involving adult medical or trauma victims. INTERVENTIONS: All participants were trained using a controlled manikin training program; then, half were randomly selected for additional instruction using fresh human cadavers. MEASUREMENTS AND MAIN RESULTS: Individuals trained using only the manikin program had mean +/- SD individual success rates of 82 +/- 32%, and individuals who received additional cadaver training had mean individual success rates of 83 +/- 31%. Overall success rates for the two groups were 86% for the manikin-only group and 85% for the manikin plus-cadaver-trained group. The sample size was not adequate to allow rejection of the null hypothesis. CONCLUSION: Paramedics trained in endotracheal intubation using a systematic manikin-only teaching program can attain acceptable individual success rates in the actual field setting. PMID- 1746735 TI - Monitoring EMS protocol deviations: a useful quality assurance tool. AB - STUDY OBJECTIVE: To determine the incidence, type, and outcome of protocol deviations in an emergency medical services (EMS) system. DESIGN: Retrospective consecutive case series. SETTING: Seven advanced life support ambulance services servicing five area hospital emergency departments. PATIENTS: 1,246 patients requiring advanced life support care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Advanced life support ambulance runs during a two-month period were examined for protocol deviations. Of 1,246 runs examined, 16% had deviations. Approximately 55% of these deviations were minor, 38% were serious, and 7% were very serious in nature. The effects of the errors were evaluated using hospital records. Results showed that 89.5% of patients were unaffected, 5.0% improved, and 5.5% suffered complications from deviations. Emergency medical technicians committed 69% of the deviations without the consent of medical control, medical control committed an additional 18%, and both were responsible in 13% of cases. Incomplete histories were found in 8% of cases. CONCLUSION: Protocol deviations committed in prehospital care do not usually cause direct harm to patients. On review of these deviations, however, several disturbing trends were uncovered, including misconceptions in the use of IV therapy, a number of serious deviations in advanced cardiac life support protocols, and lack of communication with medical control. This type of quality assurance study has the ability to identify areas of strength and weakness in an EMS system, allowing planning of ongoing educational efforts in the system. PMID- 1746736 TI - An optically scanned EMS reporting form and analysis system for statewide use: development and five years' experience. AB - Analysis of emergency medical services (EMS) systems data is crucial to planning, education, research, and quality assurance programs. Currently, comparative analysis of EMS data between regions or states is virtually impossible due to wide variations in data collection and analysis methods. To devise a practical and uniform EMS reporting system, we referenced the minimum data set (MDS) established by the federal government in 1974 and surveyed 22 states known to be using uniform reporting systems. In developing our final data set, elements were added based on inclusion in the MDS, national survey results, a review of current EMS literature, and consensus of local EMS providers. This set of 48 elements then was incorporated into a reporting form using narrative and optically scanned formats, allowing automated data collection for computer analysis. After a pilot study, the system was improved to allow high-speed ink reading and large volume data storage and analysis using a microcomputer. This system has subsequently been adopted by seven states. The combined data base exceeds 250,000 cases. Error screening algorithms ensure data integrity and are also used for quality assurance. Customized output reports can be generated within minutes and have assisted in EMS quality assurance, planning, and research. We believe that the successful performance of this system supports the use of the suggested data elements as well as optical scanning and microcomputer analysis of EMS data. PMID- 1746737 TI - Lights and siren: a review of emergency vehicle warning systems. AB - Emergency medical services providers routinely respond to emergencies using lights and siren. This practice is not without risk of collision. Audible and visual warning devices and vehicle markings are integral to efficient negotiation of traffic and reduction of collision risk. An understanding of warning system characteristics is necessary to implement appropriate guidelines for prehospital transportation systems. The pertinent literature on emergency vehicle warning systems is reviewed, with emphasis on potential health hazards associated with these techniques. Important findings inferred from the literature are 1) red flashing lights alone may not be as effective as other color combinations, 2) there are no data to support a seizure risk with strobe lights, 3) lime-yellow is probably superior to traditional emergency vehicle colors, 4) the siren is an extremely limited warning device, and 5) exposure to siren noise can cause hearing loss. Emergency physicians must ensure that emergency medical services transportation systems consider the pertinent literature on emergency vehicle warning systems. PMID- 1746738 TI - The role of military emergency physicians in an assault operation in Panama. AB - The December 1989 assault in Panama provided an opportunity to examine the role of emergency physicians in low-intensity military operations. Emergency medicine specialists accompanied the assault forces and established casualty collection points (CCPs) at each target. Emergency physicians played a role in triage, resuscitation, and aeromedical evacuation. More than 275 casualties were resuscitated and stabilized at the CCPs. Two died after reaching a CCP. Casualties were flown from each CCP to a joint casualty collection point (JCCP). Surgical stabilization was required for 21 casualties at the JCCP. A team at the JCCP coordinated evacuation of casualties to the United States. The first casualties arrived at hospitals in Texas within 12 hours of the assault. From the drop zones through hospitalization in the United States, emergency physicians cared for combat casualties at every level of the evacuation system. The success of the medical plan for the assault suggests that the role of emergency physicians in military operations extends from the front lines to fixed medical facilities in the United States. PMID- 1746739 TI - Management guidelines for health care workers exposed to blood and body fluids. AB - The purpose of this article is to propose specific management guidelines for the immediate emergency department and subsequent occupational health treatment of health care workers (HCWs) following accidental exposures to blood or body fluids. These guidelines are based on a collective review of the literature and the recommendations of the Advisory Committee on Immunization Practices (ACIP) and authorities expert in this knowledge domain. Guidelines are needed to assure appropriate treatment and coordinated efforts by ED and occupational health providers. Although numerous infections can potentially be transmitted by exposure to blood and body fluids, these guidelines are intended only for evaluation and postexposure prophylaxis of hepatitis B, hepatitis C, and infection with HIV. PMID- 1746740 TI - Prophylaxis with zidovudine (AZT) after exposure to human immunodeficiency virus: a brief discussion of the issues for emergency physicians. AB - Sound scientific information with which to determine the true efficacy of zidovudine for prophylaxis will probably not be available soon. Physicians should educate themselves thoroughly on the issues. It is highly recommended that thoughtful discussions of the issue of transmission of HIV from health personnel to patients as well as the key articles cited in this discussion be read. The details of a prophylaxis program, including laboratory evaluation, are provided in an article by Henderson and Gerberding and in greater detail in the article by Go et al. (Health care workers exposed to HIV can be enrolled in the Centers for Disease Control surveillance program by calling 404/639-1644. To enroll persons with large exposures to HIV in the zidovudine prophylaxis study, call 800/537 9978.) ED directors should work closely with local infectious disease specialists to determine if such a program is needed and how to implement it. Further details regarding the implementation of a prophylaxis program should be obtained from the literature and the Centers for Disease Control. All of the details of such a program should be worked out well in advance so that knowledgeable and immediate counseling can be provided to health care workers within one or two hours of exposure. Highly qualified individuals and institutions vary in their recommendations on prophylaxis, although most provide them. Zidovudine probably does not provide very effective protection, if it provides any. However, the medical, social, and economic consequences of HIV infection of health care workers are very real, and the serious irreversible adverse effects of zidovudine are very rare.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746741 TI - Hemorrhagic shock and encephalopathy syndrome. AB - Hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating symptom complex that affects previously healthy infants and is associated with significant mortality and neurologic morbidity. The syndrome was first reported less than ten years ago, and there continues to be debate regarding whether HSES actually represents a distinct clinical entity or instead is a manifestation of heat illness, occult sepsis or endotoxic shock, or perhaps toxic ingestion. Nevertheless, the signs and symptoms described as HSES present in a typical fashion in the emergency department with sudden onset of shock, encephalopathy, seizures, and coagulopathy. Even with the initiation of intensive support in the ED, the outcome is probably dismal. We describe a case of HSES and review the presentation, proposed etiologies, and management of this catastrophic illness. PMID- 1746742 TI - Isolated intraperitoneal bladder rupture in patients with alcohol intoxication and minor abdominal trauma. AB - Rupture of the urinary bladder secondary to abdominal trauma is uncommon and is usually associated with visceral or bone injuries; less than 10% of all cases occur without associated injuries. We present two cases of bladder rupture in intoxicated patients after minor abdominal trauma and without evidence of associated injuries. Given the absence of any symptoms in either case, we did not initially suspect bladder rupture. One of the two patients also presented with an intravesical herniation of the rectosigmoidal junction. PMID- 1746743 TI - Unstable occult cervical-spine fracture. AB - Recognition of injuries to the cervical spine is of critical importance. Such injuries may be difficult to recognize in patients who have an altered level of consciousness or other significant injuries. We present the case of an alert ambulatory patient with no complaint of neck pain, no tenderness of the neck on physical examination, and no history of trauma who, while being evaluated for fever, was found to have an unstable cervical-spine fracture that was not present on radiographs done one year earlier. PMID- 1746744 TI - Female urethral injury secondary to blunt pelvic trauma. AB - Urethral injury after blunt pelvic trauma is rare in women. We report a case of urethral injury and vaginal laceration secondary to blunt pelvic trauma. Pelvic examination should be performed in any female patient who has sustained blunt pelvic trauma to avoid the morbidity associated with delayed diagnosis of urethral injury. PMID- 1746745 TI - HIV-infected health care providers: legal rights and protections. PMID- 1746746 TI - EMS data collection: filling in the dots. PMID- 1746747 TI - The role of neuroimaging in minor head injury. PMID- 1746748 TI - Emergency care guidelines. American College of Emergency Physicians. PMID- 1746749 TI - Questions & answers: statistical tests & consent. PMID- 1746750 TI - Preventing prescription fraud. PMID- 1746751 TI - RN copes with HIV infection: she was infected while providing emergency care. Interview by Terry Selby. PMID- 1746752 TI - New rules expand role of NPs, CNSs. PMID- 1746753 TI - Fassbinder testifies on personal struggle. PMID- 1746754 TI - RNs oppose mandatory HIV testing. PMID- 1746755 TI - AIDS report urges health care for all. PMID- 1746756 TI - Position statement on HIV testing. PMID- 1746757 TI - Position statement on personnel policies and HIV in the workplace. PMID- 1746758 TI - HIV exposure demands immediate action. Position statement on post-exposure programs in the event of occupational exposure to HIV/HBV. PMID- 1746759 TI - HIV client won't tell sex partners. PMID- 1746760 TI - Payment reforms will affect RNs' practice. PMID- 1746761 TI - Small victories count in cancer fight. PMID- 1746762 TI - Needlestick leads Chicago RN to form peer support system. PMID- 1746763 TI - Testing alone won't stop HIV spread. As I see it. PMID- 1746764 TI - Know your value, what you want. PMID- 1746765 TI - Mid-Atlantic offers urban, rural opportunities. PMID- 1746766 TI - RNs, consumers--a natural alliance. PMID- 1746767 TI - Nurses and HIV. PMID- 1746768 TI - New ANA will move to D.C. PMID- 1746769 TI - A reconsideration of testing for competence rather than for intelligence. AB - David C. McClelland's 1973 article has deeply influenced both professional and public opinion. In it, he presented five major themes: (a) Grades in school did not predict occupational success, (b) intelligence tests and aptitude tests did not predict occupational success or other important life outcomes, (c) tests and academic performance only predicted job performance because of an underlying relationship with social status, (d) such tests were unfair to minorities, and (e) "competencies" would be better able to predict important behaviors than would more traditional tests. Despite the pervasive influence of these assertions, this review of the literature showed only limited support for these claims. PMID- 1746770 TI - Transforming the debate about child care and maternal employment. AB - Over the past two decades, the large-scale entrance of women into the work force has fundamentally changed the fabric of work and family life. Unlike 75 other nations, the United States has no comprehensive family policy that helps families cope with the competing demands of work and family. Research within psychology has not been helpful in pointing out the need for a major shift in public policy. This article argues that both governmental policy and psychological research reflect the popular culture's idealized myth of motherhood. It suggests an interruption of the research agenda that searches for negative consequences of maternal employment and alternative child care. A new agenda is proposed that would document the negative consequences of not providing high-quality, affordable day care. This new agenda would also acknowledge the centrality of fathers and family process to developmental outcomes in children. PMID- 1746771 TI - Co-occurring disorders among mentally ill jail detainees. Implications for public policy. AB - Studies have demonstrated that police often arrest the mentally ill when treatment alternatives would be preferable but are unavailable. Thus, jails may contain disproportionate numbers of severely mentally ill persons who have co occurring disorders. Data on the co-occurrence of severe mental disorder, substance abuse, and antisocial personality disorders were gathered from 728 randomly selected male urban jail detainees. Using difference of proportions tests and loglinear analysis, the authors demonstrated that most subjects with a severe mental disorder (schizophrenia or a major affective disorder) also meet criteria for a substance abuse or antisocial personality disorder. These findings suggest several changes in public policy regarding health care delivery in correctional settings and for the general population. PMID- 1746772 TI - Resolving legal questions with psychological data. AB - Psychologists are ever finding new legal arenas for their psychological data and concepts. Findings about the character and operation of stereotyping have been introduced in sex discrimination litigation in the United States. Findings about conformity, obedience to authority, and bystander apathy have been introduced into death penalty cases in South Africa. These concrete and detailed applications of psychological science demonstrate the expanding role that psychology is playing in the legal world. PMID- 1746773 TI - Crowd psychology in South African murder trials. AB - South African courts have recently accepted social psychological phenomena as extenuating factors in murder trials. In one important case, eight railway workers were convicted of murdering four strike breakers during an industrial dispute. The court accepted conformity, obedience, group polarization, deindividuation, bystander apathy, and other well-established psychological phenomena as extenuating factors for four of the eight defendants, but sentenced the others to death. In a second trial, death sentences of five defendants for the "necklace" killing of a young woman were reduced to 20 months imprisonment in the light of similar social psychological evidence. Practical and ethical issues arising from expert psychological testimony are discussed. PMID- 1746774 TI - Endometriosis mimics general surgical disease. AB - Endometriosis is rarely encountered by the general surgeon but may on occasion mimic general surgical disease. Although usually diagnosed easily because of cyclic symptoms and typical physical findings, six atypical cases are presented. These cases were diagnosed as appendicitis (2), subcutaneous mass (2), pelvic wall malignancy, and lower gastrointestinal hemorrhage. Diagnosis was ultimately made by laparotomy or excisional biopsy in five cases and by fine needle aspiration in one. Resection of the lesion, if feasible, is often curative. If resection is not feasible, therapy depends on the severity of the symptoms, and the patient's desire for fertility. Recognition of the typical appearance of an endometrioma may avoid mistaking it for cancer. PMID- 1746775 TI - Adverse surgical outcomes among patients with cognitive impairments. AB - To determine the factors that contributed to adverse outcomes, the records of 59 cognitively impaired patients with nonfatal complications (n = 23) or death (n = 36) on a general surgery teaching service over a 30-month period were examined retrospectively. Specific complications are reported. Patient, disease, and management factors related to mortality and morbidity are identified. Patients with cognitive impairments had a higher mortality rate (9.6 vs 6.3%) and approximately the same rate of nonfatal complications (6.1 vs 7.6%) when compared with general surgery patients as a whole. Patient characteristics including age over 70, dementia, nursing home residence, contractures, inability to communicate, need for total care, and gross malnutrition were associated with fatal outcomes. Vascular, colonic, esophageal, gastric, or duodenal conditions, emergency admission, urgent operation, and admission APACHE II scores greater than or equal to 15 were disease-related factors associated with mortality. Management risk factors were prehospital or inpatient diagnostic delays and technical or judgmental errors of surgical management. Twenty-four of 36 deaths were directly related either to a diagnostic delay (11), an operative technical error (11), or a judgmental error of postoperative airway management (2). Eighty five per cent of diagnostic delays (11/13) and 37 per cent (11/30) of technical errors resulted in mortality. Suggestions for improving the care of these patients are discussed. PMID- 1746776 TI - Measurement issues in evaluating physicians' practice patterns using hospital billing and surgeon's self-report data. AB - The availability of computerized case mix data, which merge medical records information and patient billing data, provide opportunity for measuring physician specific practice patterns. However, the validity of physician comparisons is a concern when total patient charges are measured at two points in time. In this physician-initiated multicenter study, comparisons using samples of uncomplicated, baseline cases, as determined from medical records chart reviews of five surgical procedures at three institutions, demonstrated a statistically significant reduction in average length of stay (ALOS) from 0.8 to 2.8 in seven of the 15 studies while total patient charges increased in 11 of the studies from one to 29 per cent. Billing data were useful in measuring ALOS and the frequency of specific laboratory tests ordered and then comparing these to physicians' self report practice. PMID- 1746777 TI - Successful use of subcutaneous recombinant human erythropoietin before cholecystectomy in an anemic patient with religious objections to transfusion therapy. AB - Use of recombinant human erythropoietin has been advocated for therapy in anemic patients with end-stage renal disease and to enhance the harvesting of autologous red blood cells from healthy patients scheduled for elective orthopedic surgery. The authors report the case of a diabetic patient with moderate chronic renal failure and cholelithiasis but whose religious beliefs forbade the use of transfusion therapy. She underwent successful cholecystectomy only after treatment with recombinant human erythropoietin. PMID- 1746778 TI - Strategies in the management of pyogenic psoas abscesses. AB - The presentation and management of eight patients with pyogenic psoas abscesses treated at the National Naval Medical Center, Bethesda, Maryland, between January 1986 and July 1989 are presented. The psoas abscesses were secondary to underlying gastrointestinal disease in six patients and sacral osteomyelitis in one patient. In one patient, the etiology of the abscess could not be determined. The average duration of symptoms in these patients was 16 days. Computed tomography was useful in identifying the abscess, defining its complexity, and planning therapy in all eight patients. Seven patients had complex, multiloculated abscesses, and one patient had a simple abscess. Extraperitoneal drainage was used in all patients. The patients with multiloculated abscesses had open surgical drainage, while the patient with the simple abscess had percutaneous catheter drainage. Most patients with a gastrointestinal etiology for their abscess underwent staged resection 3 to 6 weeks after the drainage procedure. There were no deaths, recurrent abscesses, or fistulae in these patients. Two patients developed thromboembolic complications postoperatively. Extraperitoneal drainage with staged resection of underlying gastrointestinal pathology is a safe and effective way of treating patients with psoas abscesses. PMID- 1746779 TI - Transderm scopolamine for the control of perioperative nausea. AB - A randomized prospective study of 201 patients in two institutions was performed to evaluate the efficacy of a transderm scopolamine patch in the control of postoperative nausea. Of 201 patients, 180 successfully completed the protocol. Demographically, the groups were similar in age, sex, and surgical procedures. Adverse effects were noted in both treatment and control groups. Forty-seven per cent of the placebo and 49 per cent of the transderm scopolamine group did not experience postoperative side effects. The most common adverse reactions were urinary retention, dry mouth, agitation, nausea, and vomiting. There was a reduction in the number of vomiting episodes in the transderm scopolamine treatment group from the control group (21% transderm scopolamine vs. 36% placebo). These differences became more significant among the subgroups in surgery, especially after orthopedic procedures. Thirty-five per cent of the transderm scopolamine group experienced nausea compared with 65 per cent from the placebo, 11 per cent of the transderm scopolamine experienced vomiting compared to 26 per cent. Transderm scopolamine was effective in reducing but not eliminating postoperative nausea. PMID- 1746780 TI - The influence of preoperative radiation therapy on morbidity and mortality for transhiatal esophagectomy. AB - To assess the morbidity and mortality of preoperative radiation therapy (RT), the authors reviewed 37 consecutive patients who underwent transhiatal esophagectomy for carcinoma of the esophagus. Twelve patients received no RT, 13 patients received RT only to the neck, and 12 received RT to the chest (three of these received radiation therapy to the chest and neck). Preoperative chest RT did not significantly increase postoperative fistula formation but was associated with significantly higher operative mortality, overall complication rate, and time on ventilators than either the patients receiving neck RT alone or no RT (P less than 0.05). Postoperative hospital stay was longer and intraoperative blood loss greater for the chest RT group compared to those with no RT (P less than 0.05). Neck RT did not result in these complications (P = NS). The authors conclude that preoperative chest RT is associated with significant postoperative morbidity and mortality. PMID- 1746781 TI - Ureteroinguinal hernia: a rare companion of sliding inguinal hernias. AB - Ureteroinguinal herniation is a rare occurrence with only 54 reported cases in the English literature. This article reviews the literature and reports on a case that typifies the problems posed by ureteroinguinal herniation. General surgeons should be aware of the potential of this condition so that they can prevent ligation or severance of the involved ureter. PMID- 1746782 TI - Esophageal obstruction and mediastinitis: a hard pill to swallow for drug smugglers. AB - Ingestion of foreign bodies is a common cause of esophageal laceration and obstruction. Mediastinitis may occur if the problem is not managed expediently. A case of upper thoracic esophageal obstruction resulting from an attempted transenteric smuggling of illicit drugs is presented. PMID- 1746783 TI - A traumatic splenic rupture in a healthy adult. AB - Splenic rupture in blunt and penetrating trauma is well documented. Other etiologies include hematologic and inflammatory disorders. The case presented documents occult splenic rupture. There was no history of trauma. Furthermore, no evidence of systemic disease or pathology could be found. Occult, spontaneous splenic rupture is rarely diagnosed, although the associated mortality/morbidity is high. The astute clinician must have a high index of suspicion relying on clinical and roentgenographic study for rapid diagnosis and management. PMID- 1746784 TI - Twenty questions about hernioplasty. AB - The twenty most asked and answered questions about advances in hernia surgery are enumerated. These inquiries have been collected over 20 consecutive years of exhibiting at a scientific booth at the American College of Surgeons conventions. The questions generally are concerned with synthetic patches, the use of local anesthesia, and, more recently, the "tension free" hernia repairs. The treatment of hernial sacs, the diagnosis, prevention and treatment of postoperative pain, the Shouldice Clinic repair, the importance of Cooper's ligament, and the cause, prevention, and treatment of recurrences are also examined. PMID- 1746785 TI - Is colonoscopy safe in the early postcolectomy period? AB - Colonoscopy was performed preoperatively and 1, 2, 3 and 7 days following a left hemicolectomy with a primary anastomosis in 11 dogs. The remaining colon and anastomosis were adequately visualized. Maximal intraluminal pressures achieved were from 15 to 35 mmHg. No leakage of air or intra-abdominal abscesses were present. In ten patients undergoing colonoscopy for lower gastrointestinal symptoms, the pressures were similarly measured. Although pressures were slightly higher in patients, averaging 30 mmHg, the results suggest that colonoscopy can be safely performed during the early postcolectomy period. PMID- 1746786 TI - Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma. AB - The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm. PMID- 1746787 TI - Superoxide dismutase polyethylene glycol improves survival in hemorrhagic shock. AB - Oxygen free radicals are known to form after reperfusion of ischemic tissue. To test the role and importance of oxygen free radicals in hemorrhagic shock, an animal model of hemorrhagic shock and resuscitation was utilized. Sprague-Dawley rats were anesthetized with halothane and then subjected to approximately 50 per cent blood volume hemorrhage (30 cc/kg), followed by a 60 min shock period. Resuscitation was performed over 1 hour with lactated ringers (LR) at a volume of two times blood loss (60 cc/kg). This model results in a survival rate of 25 per cent over 72 hrs. Using this model, animals were randomized to receive either LR, Superoxide Dismutase-Polyethylene Glycol (SOD-PEG) (15,000 units/kg) with LR or Catalase-Polyethylene Glycol (CAT-PEG) (175,000 units/kg) with LR. The group treated with SOD-PEG demonstrated significantly increased survival rates vs the group treated with LR (67% vs 25%, P = 0.02). The group treated with CAT-PEG demonstrated no significant improvement in survival when compared to the LR treated group (20% vs 24%). These data suggest that treatment directed toward oxygen free radicals and reperfusion injury may play an important role in hemorrhagic shock resuscitation. PMID- 1746788 TI - Three dimensional vascular ultrasound imaging. AB - Intravascular ultrasound (IVUS) is a new catheter-based system that produces two dimensional (2D) images of vascular structures. Existing systems produce real time, cross-sectional "slices" of vessels using 5.0 French (Fr) (30 MHz) and 8.0 Fr (20 MHz) IVUS catheters containing ultrasound transducers at the tip. Computerized, three-dimensional (3D) reconstruction of these 2D images using a personal computer- (PC) based image analysis system is described. A set (n = 90) of longitudinally aligned, consecutive images is sampled from a 5.0 cm vessel segment, and computerized processing creates rendered 3D images. By adjusting image density threshold and viewing angle, the morphology, location, and spatial distribution of arterial pathology can be seen. Refinements in computer hardware and software have reduced processing time and improved image resolution to the point where 3D IVUS imaging is a clinically applicable tool. Possible applications include diagnosis of complex arterial pathology, guidance of intraluminal instruments, and assessment of the effects of endovascular interventions. PMID- 1746789 TI - A review of carotid endarterectomy at a large teaching hospital. AB - Before 1981, the neurologic morbidity and mortality associated with carotid endarterectomy (CEA) in the Los Angeles County/USC Medical Center public teaching institution was 20 per cent, similar to results from other hospitals. In 1981, a standardized protocol was adopted in an attempt to improve surgical outcome following CEA. Between 1981 through 1990, 89 patients with a mean age of 60.9 years (range 38 to 80 yrs) had 100 consecutive CEAs. Atherosclerotic risk factors included hypertension in 57 patients (61.8%), tobacco use in 57 (64.0%), and diabetes mellitus in 28 (31.5%). Forty-nine patients had a history of ischemic heart disease. Indications for CEA were stroke in 40 cases, transient ischemic attack in 33 cases, and asymptomatic, high-grade stenosis of the internal carotid artery (greater than 85 per cent) in 19. Perioperative and surgical management are detailed in the authors' protocol. Intraluminal shunts were routinely used (99 cases) and 24 arteriotomies were patched. Completion arteriograms were performed in 99 cases, four of which were revised because of arteriographic abnormalities. Three patients sustained postoperative ipsilateral neurologic events. Ten patients had cranial nerve palsies, six of which were transient. Two patients had nonfatal postoperative myocardial infarctions. There were no deaths. The combined stroke and transient ischemic attack (TIA) mortality rate was 3 per cent. In conclusion, the audit and quality assurance process identified unacceptable results following CEA. A protocol was developed that addressed pre, intra, and postoperative details of patient selection, operative technique, and postoperative care. By adhering to the protocol, the major neurologic morbidity and mortality rate has been reduced to 3 per cent. PMID- 1746790 TI - Early absorption of enteral ranitidine after major laparotomy. AB - Thirty-six patients were studied following abdominal aortic surgery to determine if a commonly used medication could be absorbed from the gastrointestinal (GI) tract in the early postoperative period. Patients were randomized into two groups: Group I received ranitidine elixir 3 mg/kg via nasogastric tube every 12 hours; Group II received intravenous (IV) ranitidine 1 mg/kg every 8 hours. Ranitidine serum levels were measured with high performance liquid chromatography 1 hour after administration of the first three doses. Gastric pH was measured every 4 hours. It was found that serum ranitidine levels generally regarded as clinically effective were achieved in both groups. Although the levels were significantly higher following intravenous (IV) administration (Group II), there were no differences in average gastric pH. The authors conclude that within 24 hours of aortic surgery enterally administered ranitidine is effectively absorbed and provides prophylaxis equivalent to IV administration of the drug at lower cost. Other medications might be deliverable via the GI tract in the early postoperative period. PMID- 1746791 TI - The role of Yersinia enterocolitica in appendicitis in the southwestern United States. AB - Infection with Yersinia enterocolitica had been associated with acute appendicitis in approximately six per cent of patients in northern European countries. However, the incidence of Y. enterocolitica in patients with appendicitis in this country is uncertain. Therefore, this study was undertaken to ascertain whether Y. enterocolitica is a possible infectious agent in appendicitis in the southwestern United States. Fifty prospective patients (35 men and 15 women) with an average age of 22.3 years (range 3 to 62 years) underwent appendectomy for presumed appendicitis. Portions of each specimen were cultured for Y. enterocolitica with highly selective media (Cefsulodin-Irgasan Novobiocin [CIN] agar). Pathologically, 44 of the patients had appendicitis and 6 patients had normal appendices. Four of the 44 patients (9.1%) with appendicitis were found to be culture positive for Y. enterocolitica, while it was recovered from none of the normal appendices. This indicates that Y. enterocolitica may represent the major pathogen in acute appendicitis in a small, but distinct, portion of indigent patients within Los Angeles County as it does elsewhere in the world. PMID- 1746792 TI - Adjunctive antimicrobials in surgery of soft tissue infections: evaluation of cephalosporins and carbapenems. AB - The authors report three trials of B-lactams and carbapenems for soft tissue infections treated on a surgical service: 1) cefmetazole versus cefoperazone, n = 44; 2) cefotetan versus cefoxitin, n = 24; and 3) meropenem versus imipenem, n = 44. A total of 138 hospitalized patients were enrolled with 112 meeting evaluability criteria. Four hundred twenty-three isolates were cultured (mean, three/patient) of which 67 per cent were aerobes and 33 per cent anaerobes. Cure rates for each trial were: 1) 93 per cent; 2) 92 per cent; 3) 100 per cent. Failures were caused by resistant organisms (Streptococcus group D, Bacteroides fragilis and Pseudomonas) appearing in incompletely drained infection sites. Three patients receiving meropenem had adverse effects (headache, nausea) and one receiving cefoxitin (truncal rash). Operative drainage and debridement remain the critical elements in therapy. Agents with longer half lives allowing twice daily dosing (cefmetazole and cefotetan) were as effective and less expensive than multiple doses of short-acting agents. The extended spectrum carbapenems are most useful for severe infections or resistant organisms. PMID- 1746793 TI - Early diagnosis and treatment of sinusitis in the critically ill trauma patient. AB - Sinusitis is an important cause of sepsis in the critically ill patient and may be difficult to diagnose. Four patients admitted to the surgical intensive care unit with closed head trauma were found to have sinusitis as the cause of persistent bacteremia. All patients received pharmacologic doses of corticosteroids for treatment of head injury and had prolonged nasotracheal and/or nasogastric intubation. A bedside procedure was used for diagnosis and management. Under local anesthesia, a 16-gauge angiocatheter was inserted under the inferior turbinate and into the maxillary sinus. After purulent fluid was aspirated, the sinuses were irrigated with normal saline. All four patients defervesced within 24 to 48 hours of this procedure, and facial x rays demonstrated clearing of the maxillary sinus. It was concluded that: 1) Sinusitis is a complication of closed head trauma in critically ill patients and should be included in the differential diagnosis when persistent bacteremia occurs; 2) The use of corticosteroids in the treatment of head injury may increase the risk of sinus infection; 3) Facial x rays showing air-fluid levels and/or opacification are a valuable screening test for paranasal sinusitis; and 4) bedside aspiration of the maxillary sinus is an effective diagnostic and therapeutic technique for management of sinusitis in the critically ill. PMID- 1746794 TI - Survival in trauma victims with pulmonary contusion. AB - The author evaluated 203 consecutive patients with severe chest trauma admitted to the trauma center between 1985 and 1989. The goal was to identify risk factors that play a significant role in mortality of patients with pulmonary contusion. There were 160 men and 43 women. The average was 33 years (range 2 to 92 years); 178 patients were younger than 60 years and 25 were older. There were 183 motor vehicle or motorcycle accidents, five gun shot wounds, one stab wound, five falls from height, three industrial accidents, one altercation, and five other undetermined causes. One hundred and fifty-nine patients survived; 44 died (22%). Their injury severity scores averaged 27 (range 9 to 59) for the survivors and 43.5 (range 17 to 75) for the nonsurvivors. Fifty-seven per cent of the patients required mechanical ventilation. The average time on the ventilator was 4.4 days (range 1 to 47 days) for the survivors and 14.2 days for the nonsurvivors (range 1 to 126 days). Of the patients less than 60 years old, 34 (20%) died, but 10 (40%) of the 25 patients older than 60 years died. Average blood loss was 1,047 cc (range 0 to 14,300 cc), but the difference was not statistically significant between survivors and nonsurvivors in the authors' series. Injuries to the central nervous system were present in 80 (40%) of the patients and were associated with death in 30 (68%) of the cases. Age, severity of injury, associated head trauma, and shock were the most important factors affecting survival in the authors' patients with pulmonary contusion. PMID- 1746795 TI - The relationship between ARDS, pulmonary infiltration, fluid balance, and hemodynamics in critically ill surgical patients. AB - Hypervolemia from fluid overload with resultant pulmonary edema is thought to be a frequent cause of Adult Respiratory Distress Syndrome (ARDS). However, ARDS may also occur as a result of the hypovolemic shock of surgery or trauma. To develop an appropriate rationale for fluid therapy in high-risk surgical patients, the relationship between fluid balance, hemodynamics, the onset of ARDS by physiologic criteria (shunt greater than or equal to 20%, and/or PaO2/FiO2 ratio less than 250) and the onset of pulmonary infiltration (PI) associated with ARDS were examined. Fifty patients were prospectively followed from admission throughout their hospitalizations; 38 (76%) had trauma and 12 (24%) were postoperative. Cardiac index, central venous pressure (CVP), wedge pressure (WP), and shunt (Qsp) were measured. All chest x rays were read by one staff radiologist who was blinded to the patients' identities. PI was graded from "0" to "4" (0 = no PI, 4 = maximum PI). The first x ray reading of "2" or greater was used as the time of onset of PI. ARDS by physiologic criteria occurred in 29 of 50 (58%) patients; 27 of these 29 (94%) also developed +2 or greater PI. The mean onset times of ARDS and of +2 PI were 40 +/- 41 hours and 40 +/- 38 hours, respectively. The ARDS patients had a significantly smaller net positive fluid balance than the non-ARDS patients over the first 40 hours after admission (+6,831 ml +/- 4,909 ml vs 12,440 ml +/- 7,817 ml, (P less than 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746796 TI - The socioeconomic impact of assault injuries on an urban trauma center. AB - In 1983, Los Angeles County designated 23 level I or II trauma centers. During the subsequent 7 years, ten centers closed because of adverse financial impact. To analyze the causes of this trend, hospital admissions for gunshot and stabbing injuries were reviewed for two separate 1-year periods at a level I urban trauma center. Of 1,160 patients arriving with injuries meeting county triage criteria from January 1, 1986 through December 31, 1986, 323 (27%) sustained penetrating assault, of which 96 were with firearms (30%). From January 1, 1988 through December 31, 1988, 1,213 met triage criteria; 301 (25%) were intentional, of which 179 (59%) were due to firearms. Epidemiologic and clinical data from the two periods is similar with 90 per cent of the patients being men ages 25 to 30 and of minority ethnic background. Seventy-five per cent of the patients required a truncal operative procedure and needed about 5.5 days of hospitalization. Overall, mortality averaged 4.7 per cent and morbidity 14.5 per cent. Complete financial data was available on 561 of the 624 intentionally injured patients for which costs totaled $2,481,346 (mean = $5,260 for gunshots; mean = $3,640 for stab wounds). The total collections were $545,896 (22% of total charges). Only 5 per cent of the charges were reimbursed from insurance; MediCal reimbursed 13 per cent and only 1 per cent was from Medicare. Eighty-one per cent of the patients had no financial resources, resulting in a hospital deficit of $1,861,009 (75% of the total charges).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746797 TI - Impact of ICU nosocomial infections on outcome from surgical care. AB - The authors studied the impact of intensive care unit (ICU) acquired nosocomial infections on surgical patients stratified by severity of illness before acquisition of the infection. Data were analyzed from 2,122 consecutive patients admitted to a 20 bed surgical intensive care unit (SICU) from January 1, 1988 to December 31, 1988. The simplified acute physiology score (SAPS), a measure of illness severity that correlates with mortality, was calculated for all patients on their first SICU day. Ninety-seven nosocomial infections from various sites were documented in 54 patients. Patients who acquired a nosocomial infection were significantly more ill upon admission to the SICU than patients who did not acquire such an infection (control patients). Stratified by admission severity of illness, patients acquiring one or more nosocomial infections had a significantly longer SICU stay, averaging 25.3 days compared to 2.3 days in control patients (P less than 0.001). Hospital stay was also significantly increased at 59.9 days, compared to 15.0 days in control patients (P less than 0.001). However, the overall mortality rate for patients developing nosocomial infections was significantly higher than control patients only in the middle range of admission SAPS measurements. The authors found that the monthly incidence of isolates of Xanthomatous maltophilia, a multiply-resistant nosocomial organism, reflected the overall incidence of nosocomial infections in the SICU. They observed a decline in the number of new X. maltophilia isolates and nosocomial infections concomitant with the introduction of gown and glove contact isolation procedures. The authors conclude that nosocomial infections in the SICU setting are directly related to increased patient morbidity and mortality depending, in part, on severity of illness upon admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746798 TI - Wound infection in patients with traumatic small intestinal injuries. AB - Delayed closure has been the traditional management of wounds in patients with traumatic colon injury, whereas small bowel injury has generally been treated with primary wound closure. Sixty-seven patients with traumatic hollow viscus injury isolated to jejunum and ileum were reviewed to determine the incidence of septic wound complications. Fifty-eight patients underwent primary wound closure with 15 (26%) developing wound infections. Nine patients had their wounds left open because of major intraperitoneal contamination with no resulting wound infection. In patients with primary closure of their wounds, there was no difference between these developing wound infections and those without with regard to the presence of hypotension, amount of spill, type of repair, site of injury, or antibiotic given. Significant difference was present regarding time between injury and surgery (8.6 vs 17.7, P = .025). Results suggest that delayed wound closure should be performed in patients with traumatic small bowel injury. PMID- 1746799 TI - The hepatorenal syndrome in liver transplant recipients. AB - The hepatorenal syndrome (HRS) is a well-known complication of liver failure, and medical treatment is usually not successful unless liver function can be improved. The authors review their experience with 130 adults undergoing orthotopic liver transplantation (OLT) over a 20-month period to determine the incidence of HRS and its effects on patient outcome, need for hemodialysis (HD), and the degree of recovery of renal function. The clinical diagnosis of HRS preoperatively was made by using criteria to exclude prerenal azotemia, acute tubular necrosis, and primary renal diseases. Nineteen patients were identified as having the HRS for a preoperative incidence of 15.1 per cent. Overall, 41 of the 126 patients reviewed required postoperative HD, and the mortality in this group was 54 per cent. Fifty-eight per cent of the HRS patients were dialyzed postoperatively vs 28 per cent of non-HRS patients. The mean posttransplant creatinine improved over time in the HRS patients while it worsened slightly in the non-HRS group. At 12 weeks posttransplant, there was a significant difference in the mean creatinine levels (1.8 +/- 0.3 mg/dl vs 1.2 +/- 0.04 mg/dl, P = .001). However, at 24 weeks the small difference was not statistically significant between the two groups (1.6 +/- 0.15 mg/dl vs 1.3 +/- 0.06 mg/dl, P = NS). The current survival of the hepatorenal group is comparable to the nonhepatorenal patients at a follow-up of 6 to 25 months: 68 per cent vs 78 per cent, P = NS. The authors conclude that liver transplantation reverses the HRS, and that hepatorenal patients can undergo liver transplantation with outcomes comparable to nonhepatorenal patients. PMID- 1746800 TI - Diaphragmatic injuries: recognition and management in sixty-two patients. AB - Between 1979 and 1989, 62 patients were treated for traumatic injury of the diaphragm. Forty-five had penetrating injuries following stab wounds or gunshot wounds, and 17 had diaphragmatic tears from motor-vehicle and auto-pedestrian accidents. Forty-one patients sustained left-sided injuries; 20 patients sustained right sided injuries; and one patient sustained bilateral ruptures. All patients underwent exploratory laparotomy and diagnosis was confirmed at surgery. Diaphragmatic injury was suspected in only 17 (27%) patients preoperatively. The chest radiograph showed nonspecific abnormalities in 48 (77%) patients and was diagnostic in 15 (24%) patients. Six patients had diagnostic peritoneal lavage; five were positive and one was negative. Computerized tomography (CT) of the lower thorax and abdomen was performed on 11 (18%) patients, but not one scan was diagnostic. Fluoroscopy in two patients was helpful. All patients had other associated injuries. The liver, spleen, or stomach were frequently injured in association with penetrating diaphragmatic lacerations. Bony fractures, splenic injuries, and head trauma were more commonly found with blunt diaphragmatic ruptures. The average hospital stay for the penetrating injuries was 11 days and for blunt trauma was 16 days. The operative mortalities was 2 per cent for penetrating injuries and 12 per cent for blunt injuries. PMID- 1746801 TI - Diffuse bile duct tumors: guidelines for management. AB - The majority of patients with bile duct cancer have small focal adenocarcinomas localized to the upper, middle, or lower third of the bile duct. In contrast, a small subgroup of patients have been identified with bile duct tumors that are diffuse, involving multiple segments of the extrahepatic biliary tract. Among 186 patients with documented bile duct cancer treated at the UCLA Medical Center between 1954 and 1988, 13 patients (7%) had diffuse lesions. Patients with diffuse tumors had markedly poorer survival rates than did those with focal lesions. As diffuse tumors are not amenable to resection, surgical management consists primarily of establishing suitable biliary drainage. All patients with bile duct cancer should undergo careful intraoperative evaluation to exclude a diffuse lesion before tumor resection. PMID- 1746802 TI - Xanthogranulomatous cholecystitis: a chronic inflammatory pseudotumor of the gallbladder. AB - Xanthogranulomatous cholecystitis is a benign chronic inflammation of the gallbladder that can morphologically mimic carcinoma. In severe cases, the diagnosis is made intraoperatively using frozen section histology and pathologic consultation. Once the diagnosis of xanthogranulomatous cholecystitis is confirmed, cholecystectomy should be performed. Occasionally, the inflammatory reaction and fibrosis within the gallbladder is so severe that conventional cholecystectomy is unsafe. In these instances, a subtotal cholecystectomy is required. PMID- 1746803 TI - Acalculous candida cholecystitis: a complication of critical surgical illness. AB - Four patients with underlying diseases including multiple trauma, aortic graft infection, and complex fistulae developed acute acalculous cholecystitis with bile cultures positive only for Candida albicans. The primary site of the candida infection included urinary tract, gastrointestinal tract, and an aortic graft in one patient each and was undetermined in the trauma victim. All had received broad-spectrum antibiotics; three of the four were in the intensive care unit (ICU) with organ failure. Ultrasonography showed a thickened gallbladder wall in three patients and sludge in one. Hepato-iminodiacetic acid scans were nonvisualizing in these three patients. Operative findings included gangrenous cholecystitis in two patients and edematous cholecystitis in one. The fourth patient was treated with percutaneous cholecystostomy and interval cholecystectomy. The interval from the onset of symptoms to recognition of the need for operation was an average of 7 days. Two of the four patients died of ongoing sepsis. Candida cholecystitis is a life-threatening complication of critical surgical illness. Risk factors are similar to those for candida infection elsewhere and include antibacterial therapy, complex fistulae, disseminated malignancy, immunosuppression, and prolonged ICU stay. A high index of suspicion for this fungal pathogen and aggressive surgical therapy offer the only chance for a favorable outcome. PMID- 1746804 TI - Transfusion therapy in cardiac surgery: impact of the Paul Gann Blood Safety Act in California. AB - The Paul Gann Blood Safety Act became law in California on January 1, 1990, mandating that patients be informed of the risks and alternatives of blood transfusions. To evaluate the impact of this legislation, the authors compared transfusion therapy in patients undergoing cardiac surgery during 1990 to previous years (1986 to 1987 and 1989). Surgical techniques were unchanged. Homologous component usage was 8.7 +/- 0.6 (mean +/- SE) units/patient in 1986 to 1987 (n = 373), 8.2 +/- 0.9 in 1989 (n = 219) and 4.3 +/- 0.6 in 1990 (n = 222), P less than .001 by ANOVA. Erythrocyte transfusions were 3.5 +/- 0.2, 3.2 +/- 0.2, and 2.2 +/- 0.2 units/patient (P less than .001); platelet/plasma usage was 5.2 +/- 0.5, 4.9 +/- 0.7 and 2.1 +/- 0.4 units/patient (P less than .001). The number of patients not requiring transfusions increased from 28 per cent in 1989 (61 of 219) to 47 per cent in 1990 (104 of 222). A slight but significant decrease in cardiopulmonary bypass time and perioperative blood loss occurred. The authors conclude that this legislation stimulated the surgical team to control blood loss during surgery and to avoid the anticipatory use of component transfusions. PMID- 1746805 TI - Time-course of cardiopulmonary effects tumor necrosis factor and endotoxin are similar. AB - Tumor necrosis factor (TNF) is a postulated proximal septic mediator. The authors compared the time course and extent of the cardiopulmonary effects of recombinant human TNF (rTNF) in swine vs those of Escherichia coli endotoxin (ETX). Intravenous boluses of either rTNF (n = 4), ETX (n = 2), or saline (n = 4) were given to swine. Mean pulmonary artery pressure and extravascular lung water (EVLW) were increased at 60 minutes for rTNF and ETX to 31 +/- 2 mmHg and 33 +/- 3 mmHg and 6.3 +/- 0.9 ml/kg and 7.1 +/- 1.6 ml/kg, while saline animals were unchanged. The authors conclude that rTNF mimics ETX both in time course and magnitude of effects. Right-sided cardiopulmonary effects predominate in both with minimal left-sided effects at these dosages. The time course of early increased EVLW suggests an initial hydrostatic influence on pulmonary edema formation in this septic model. PMID- 1746806 TI - Health, hygiene, work and wealth--Warner Lecture 1991. PMID- 1746807 TI - Studies on the cytotoxicity of ceramic respirable dusts using in vitro and in vivo test systems. AB - The effect of a number of ceramic raw materials and airborne samples in workplaces has been investigated in vitro [erythrocyte haemolysis, macrophage TTC (2,3,5-triphenyl-tetrazolium chloride) reduction and LDH (lactate dehydrogenase) activity] and in vivo (protein, LDH and phospholipid in cell-free bronchopulmonary lavage). In the in vitro experiments described we were able to distinguish between the dusts causing different types of reaction in the lung. Dusts classified as 'quartz type' in vitro were also cytotoxic in vivo. Dusts have also been divided into three groups according to their degree of hazardous nature, taking into consideration the time before an inflammatory reaction is detected and the degree of inflammatory response as characterized by biochemical parameters. One feature of the test systems which is of practical significance is that in vitro experiments require only 15 mg of dust, and in vivo experiments only 100 mg. PMID- 1746808 TI - Comparison of measured respirable dust sampler penetration curves with sampling conventions. AB - Measured sampler penetration curves are presented for British personal cyclone samplers and the MRE 113A static horizontal elutriator in calm air. These curves are compared with previous results for these instruments, and with theoretical models of sampler behaviour. The sampling efficiency of the elutriator when facing a moderate wind is discussed. The penetration curves are assessed by comparison with standard sampling conventions for respirable dust. PMID- 1746809 TI - Posture control and the risk of industrial accident: a stabilographic investigation in a naval shipyard. AB - In a previous case-control study on the effect of impaired perceptual acuity on the risk of industrial injuries at a naval shipyard, three factors which might influence the perception and processing of sensory impressions--alcohol consumption, hearing loss exceeding 20 decibels (dB) and exposure to noise exceeding 82 dB(A)--were found to contribute to the risk of injury. According to recent reports, these factors can all lead to impaired posture control. Because in general about 40% of all accidents are associated with falling, tripping, slipping and the like, a supplementary study has been carried out to unravel possible confounding effects of posture control on these three risk factors. Cases (who had suffered two or more accidents during the preceding 4 years) and controls (who had been accident-free in the same period) were compared as regards posture control measured during silence or noise. No significant difference in posture control was found between cases and controls, either in silence or during exposure to heavy noise. PMID- 1746810 TI - Study of the count-to-mass conversion factor for asbestos fibres in samples collected at the emissions of three industrial plants. AB - Count-to-mass conversion factors for asbestos fibres in the stack emissions of three industrial plants were calculated. Dust samples deriving from different working processes were collected downstream from the fabric-based filtration systems. Gravimetric measurements were carried out utilizing an X-ray diffraction procedure based on the use of a silver filter that permits the correction for X ray absorption by the sample. The number of fibres covered by regulations ('Regulated fibres') (F) was counted by phase-contrast optical microscopy (PCOM) on a section of the same filter as had been used for gravimetric measurements. The values of the conversion factors vary widely, ranging from 0.4 x 10(3) to 4.9 x 10(3) fibers per microgram (F microgram -1) according to the working process involved. They are always less than 20 x 10(3) F microgram -1, the value specified in the EEC Directive 217/87 concerning the prevention of asbestos pollution in the environment. PMID- 1746811 TI - The effect of environmental factors on the pharmacokinetic behaviour of organic solvent vapours. AB - A review of the literature concerning environmental factors affecting toxicokinetic behaviour of organic solvents revealed that alcohol consumption and exposure to other organic solvents are of great importance among such factors. An insight into how environmental factors affect the toxicokinetic behaviour of organic solvents is discussed by modelling (a) the effect of alcohol consumption on the toxicokinetics of trichloroethylene (TRI), and (b) the effect of the metabolic interaction between benzene and toluene. In general, hepatic metabolism of an organic solvent (substrate) is assumed to follow the Michaelis-Menten equation, v = Vmax.S/(Km + S), where v is the rate of substrate metabolism, Vmax and Km the maximum velocity and Michaelis constant for the metabolism, respectively, and S the substrate concentration in the liver. On the assumption of competitive inhibition, inhibition of the substrate metabolism by the simultaneous presence of ethanol or other organic solvents (inhibitors) can be expressed as follows: v = Vmax.S/[Km + (Km/Ki)I + S] where I is the inhibitor concentration in the liver and Ki the inhibitor constant toward the substrate metabolism. An increase in Vmax without a change in Km can represent enzyme induction due to alcohol consumption or previous repetitive exposure to other solvents. A simulation study on the effect of alcohol consumption on the metabolism of TRI revealed that the lower the exposure concentration, the larger the inhibitory effect of ethanol. In contrast, the effect of enzyme induction following alcohol consumption makes its full appearance only when the exposure concentration is high. Another simulation study on the mutual metabolic interaction between benzene and toluene suggested that at low exposure concentrations of both benzene and toluene where enzymes are supposed to have in reserve some capacity to catalyse the metabolism of both solvents, each solvent inhibits only slightly the metabolism of the other. On the other hand, at high exposure concentrations where enzymes have little or no capacity in reserve, the simultaneous presence of benzene and toluene notably suppresses the metabolism of each other. PMID- 1746812 TI - Pharmacokinetic models in the development of exposure indicators in epidemiology. AB - Physiological pharmacokinetic (PK) models can estimate tissue levels from data on blood solubility, partition coefficients and metabolic rate(s) of a chemical agent. Use of these models in epidemiological studies has been limited. PK models can be useful if four conditions are met: (1) potential causal agents are identified; (2) groups of subjects with substantially different profiles of exposure intensity are identified; (3) a physiological PK model is available to extrapolate target tissue concentrations for potential agents; and (4) mechanistic hypotheses predict substantially different risk for different time profiles of tissue concentration. An example of this approach is presented for cancer risk from mixed hydrocarbon exposures, including the development of three practical dose indices. This use of PK models produces dose-response relationships useful for risk assessment, and it permits epidemiological evaluation of mechanistic hypotheses derived from laboratory studies. PMID- 1746813 TI - Ocular thrombosis associated with antiphospholipid antibodies. AB - Four patients with isolated acute ocular ischemic syndromes also had circulating antiphospholipid antibodies. Two patients had vaso-occlusive retinopathy and two, anterior ischemic optic neuropathy (which was successive in one). Extensive clinical laboratory evaluation identified vascular risk factors in two patients. One patient had essential thrombocytosis, confirmed by bone marrow biopsy; the other had stable hypertension and a history of coronary artery disease. These cases suggest that small vessel thrombosis in situ may be a mechanism for antiphospholipid-associated ocular and cerebral ischemia. PMID- 1746814 TI - Recurrent uveitis after influenza vaccination. AB - A 77-year-old woman had complicated cataract surgery with resultant uveitis. Four months after an apparently complete recovery, she was vaccinated with influenza vaccine. Within two weeks, she had a recrudescence of her inflammation accompanied by cystoid macular edema and reduced vision. We discuss the mechanisms of this reaction. PMID- 1746815 TI - Effect of topical corticosteroids on goblet-cell density in an alkali-burn model. AB - Conjunctival alkali burns result in a loss of goblet cells in the acute postinjury period. A deficiency of goblet cells and their primary product, mucin, is associated with both short- and long-term ocular sequelas. We evaluated the effect of topical corticosteroids on goblet-cell density in a prospective, randomized, controlled trial using 24 eyes of 12 adult albino rabbits in which a standard conjunctival burn was made. The treatment group was found to have 97.38 goblet cells per unit area of conjunctiva; the control group had 65.81 goblet cells per unit area of conjunctiva. This was a statistically significant difference (P less than .02). These results suggest that topical steroids are beneficial in suppressing goblet-cell loss after a conjunctival alkali burn. PMID- 1746816 TI - Regulating the dose of 5-fluorouracil to prevent filtering bleb scarring. AB - Repeated doses of 5mg of 5-fluorouracil (5-FU) were injected subconjunctivally in 25 poor-prognosis glaucomatous eyes after filtering surgery to prevent filtering bleb scarring. The frequency (1-2 times a day) and duration (minimum, 7 days) of injections were determined by the degree of the anterior chamber reaction and/or conjunctival hyperemia at the filtering bleb site. Punctate corneal erosions or filaments were not considered a contraindication to continuation of 5-FU treatment. After 12 months, intraocular pressure (IOP) of 16 mmHg or less without medical treatment was found in 19 (76%) eyes. In 16 of these (64%), the IOP was 12 mmHg or less. In two (8%) other eyes, it was 20 mmHg or less with medication. We believe that the comparatively low IOP levels achieved without medical treatment in 76% of the eyes in our study can be attributed in part to our therapeutic approach with 5-FU. PMID- 1746817 TI - Orbital and sinus inflammation with secondary optic neuropathy. AB - Optic neuropathy with simultaneous orbital and sinus inflammation is a diagnostic dilemma. Although sinus inflammation was described previously as causative in some cases of optic neuritis, the relatively high rate of asymptomatic sinus opacification in radiologic studies of the general population (as high as 13%) makes this a diagnosis of exclusion. We describe a patient who had optic neuropathy associated with simultaneous orbital and sinus inflammation. Although definitive determination of etiology may not be made without tissue biopsy, cases suspected of having a bacterial etiology may benefit from an initial 48-hour trial of intravenous antibiotics before initiation of systemic corticosteroids. PMID- 1746818 TI - Infectious keratitis in Baltimore. AB - One hundred thirty cases of ulcerative keratitis occurring from 1985 to 1989 at Sinai Hospital of Baltimore were reviewed. Positive corneal cultures were obtained from 40% of cases. The most common isolates were Staphylococcus epidermidis (28%), S. aureus (16%), and Pseudomonas aeruginosa. P. aeruginosa was the most common in contact lens wearers. Antibiotic pretreatment did not affect the rate of positive cultures significantly. Bilateral conjunctival and eyelid margin cultures also were examined. An association was found between corneal and ipsilateral conjunctival isolates (P = .05). Gram stains were consistently negative. Most patients were treated successfully as outpatients. The value of simultaneous conjunctival and eyelid margin cultures and Gram stains was questioned. PMID- 1746819 TI - Psychological change following 18 months of cochlear implant use. AB - Consecutive recipients of multichannel cochlear implants participated in preimplant as well as 9-month and 18-month psychological evaluations. Before receiving a cochlear implant, psychological tests indicated that the implant recipients were more depressed, suspicious, socially isolated, lonely, and socially anxious than was the general population. After 18 months of implant use, there was a significant reduction in depression, loneliness, social anxiety, social isolation, and suspiciousness. These changes in psychological state did not correlate with improved performance on audiological measures. The data suggest that although cochlear implants can have a positive effect on the emotional and behavioral status of persons with acquired postlingual profound deafness, the psychological outcome of implants is not simply a function of the audiological benefit assessed with standardized speech-based audiological tests. PMID- 1746820 TI - Effect of age at onset of deafness on children's speech perception abilities with a cochlear implant. AB - The speech perception abilities of 37 children with cochlear implants (single channel or multichannel) were examined as a function of age at onset of deafness. There was no significant difference in the speech perception abilities of implanted children who were born deaf and those of implanted children who lost their hearing during the first 3 years of life. In contrast, the performance of children whose age at onset of deafness was 5 years or later was significantly better than that of the children with congenital or early-acquired deafness on tests of stress pattern categorization, closed-set word identification, open-set identification of common phrases, and lipreading enhancement. PMID- 1746821 TI - Round window versus promontory stimulation: assessment for cochlear implant candidacy. AB - Electrical stimulation of the cochlea is a part of the preliminary evaluation protocol for cochlear implant candidacy at many centers. Typically, a transtympanic needle electrode is placed on the promontory of the ear under consideration and electrical current is presented to measure auditory percepts and psychophysical-electrophysiologic measures. Since 1984, we have used a ball electrode placed directly on the round window (via a tympanotomy) for stimulation, with 27 subjects being so tested to date. Nine additional subjects have had stimulating electrodes placed on both the round window and the promontory. Seven of these subjects yielded complete data. For measurements of threshold, maximum acceptable loudness level, and dynamic range, promontory testing mean values were higher than round window measurements. However, the differences were not significant. PMID- 1746822 TI - Indication of a relation between speech perception and temporal resolution for cochlear implantees. AB - In order to better understand the reasons for success or failure of a cochlear implant system for various patients, it appears necessary to analyze the patients' basic psychophysical capacities in relation to speech perception. Five patients with intracochlear multichannel Ineraid implants were studied in terms of their performance on temporal analysis in relation to their perception of consonants. For temporal analysis we measured the detection of a silent gap in noise and of an interval between two clicks. For consonant perception we established a confusion matrix based on 12 consonants presented in a vowel consonant-vowel context using the vowel /a/. The results showed a correlation between temporal resolution for two successive clicks at the most basal cochlear electrode used, and the perception of place of articulation of consonants. This finding indicates that delivering fine temporal coding can be crucial for the success of an implant and that for a given subject, optimal capacity for temporal resolution may serve as a criterion for choosing a basal electrode. PMID- 1746823 TI - Prediction of behavioral threshold and comfort values for Nucleus 22-channel implant patients from electrical auditory brain stem response test results. AB - We have studied the prediction of behavioral threshold and comfort values for 11 patients who use the Nucleus 22-channel cochlear implant by means of the results of electrical auditory brain stem response (EABR) procedures. For prediction purposes, EABR and behavioral testing were done in the same electrode mode configuration for three specific electrodes. The results of this investigation suggest that EABR threshold current level is consistently near the behavioral comfort current level, rather than the patient's behavioral threshold level. PMID- 1746824 TI - Laryngeal manifestations of gout. AB - Gout is a disorder of purine metabolism characterized by hyperuricemia with rare involvement of the head and neck. We present a 72-year-old woman with a known history of gout who presented with hoarseness and a lesion suspicious for carcinoma of the larynx. Endoscopic biopsy revealed a tophus of the true vocal cord with characteristic birefringent crystalline deposits and giant cell granuloma. There have been limited reports of gouty involvement of the larynx, more commonly involving cricoarytenoid arthritis. Tophi of the laryngeal soft tissues are exceedingly rare. In this paper we will discuss the pathophysiology and management of this interesting clinical entity. PMID- 1746825 TI - Causes of childhood deafness at a Dutch school for the hearing impaired. AB - This study was conducted on 162 hearing-impaired school pupils who were investigated as to the cause of their hearing loss. In 64 pupils (40%) a hereditary cause was recognized, and in 43 (27%), an acquired cause; in 55 (34%) the cause remained unknown, according to the criteria we used for defining a cause. Special attention was paid to the differences between the hereditary and acquired forms of deafness in relation to the degree of hearing loss. The study population therefore was divided into groups per 10 dB of hearing loss. Using this method we found that an autosomal dominant hearing loss occurred significantly more frequently among the less severe hearing disorders. This finding, which has not been seen in the literature, is important in genetic counseling for the deaf. Another remarkable finding was that Usher's syndrome, especially type 2 with a moderate hearing loss, was more frequent among the hearing-impaired subjects than we had expected. PMID- 1746826 TI - Abnormalities of lateral cartilaginous lamina and lumen of eustachian tube in cases of cleft palate. AB - Development of the lateral lamina (LL) of the eustachian tube (ET) cartilage was investigated in cleft palate (CP) cases and controls by measuring the areas of the LL and medial lamina (ML) of the ET cartilage in histologic cross section, and comparing the ratio of the area of LL to that of ML (LL/ML) in CP cases and controls. The degree to which the ET lumen appeared straight or C-shaped in cross section was also measured. Thirty temporal bones with the entire ET--10 CP cases and 20 controls--were studied. The ratio of the areas of the ET cartilage was significantly smaller (t = 2.903, p less than .01) and the curvature of the ET lumen was significantly less (t = 2.080, p less than .05; chi 2 = 3.936, p less than .05) in CP cases than in controls. In addition, in all 30 CP cases and controls, the ratio of the areas of cartilage was significantly less in specimens with straight ET lumens than in those with C-shaped lumens (t = 2.713, p less than .02). The results appear to show that the ET cartilages and lumens are anomalous in CP cases. These anomalies are considered to be important factors in active ventilatory dysfunction of the ET. PMID- 1746827 TI - Evaluation of the temporal bones of a multichannel cochlear implant patient. AB - In this report we detail the temporal bone findings of a 57-year-old patient who underwent placement of a Nucleus 22-channel electrode 7 months prior to his death. Audiometric testing postoperatively demonstrated suprasegmental speech cue discrimination only. Histologic evaluation of the cochleas revealed significant sensorineural survival except in the region of the basal turn of the implanted cochlea adjacent to the implant. There was no significant pathologic condition attributable to the operation or the electrode in areas remote from the basal turn of the cochlea. PMID- 1746828 TI - Airway obstruction and high-frequency jet ventilation during laryngoscopy. AB - High-frequency jet ventilation has been reported as an effective method of ventilation during laryngoscopy, but may expose the patient to the risks of barotrauma or alveolar hypoventilation. The aim of the study was to evaluate the determining factors of pulmonary complications under high-frequency jet ventilation in 83 patients undergoing laryngoscopy for upper airway cancer. Pulmonary distention was mainly influenced by upper airway obstruction score (p = .0001), while patients with chronic obstructive pulmonary disease (COPD) did not suffer from gas trapping. Impaired gas exchange was predicted by increased weight (p = .0001), smaller injector diameter (p = .02), and lower airway obstruction (p = .001). Hypercapnia occurred in both upper and lower airway obstruction, while hypoxemia was principally observed in COPD patients. Emphasis is placed on monitoring by pulse oximetry, end-expiratory pressure, and PCO2 measurement, especially in patients with obesity, COPD, or upper airway obstruction. PMID- 1746829 TI - Congenital conductive or mixed deafness, preauricular sinus, external ear anomaly, and commissural lip pits: an autosomal dominant inherited syndrome. AB - Branchiogenic syndromes such as branchio-oto-renal syndrome, Treacher Collins syndrome, and hemifacial microsomia are well delineated. From a clinical study in a large family spanning three generations, it can be concluded that the association of conductive deafness, commissural lip pits, preauricular sinuses, and external ear anomalies can be differentiated from the above-mentioned syndromes and is a separate autosomal dominant syndrome. PMID- 1746830 TI - Glycoconjugates in the chinchilla tubotympanum. AB - Various biotinylated lectins were used to characterize and semiquantitate glycoconjugate residues in the tubotympanum. Epithelial goblet cells were stained predominantly by WGA, LFA, SNA, RCA-I, Con-A, LCA, SBA, PHA-E, and UEA; this finding suggests they contain alpha-neuraminic acid, beta-galactose, alpha mannose, N-acetyl alpha-galactosamine, and alpha-fucose. Glandular mucous cells were stained predominantly by WGA, LFA, SNA, and RCA-I; this finding suggests that they contain alpha-neuraminic acid and beta-galactose. The glandular serous cells were stained predominantly by Con-A, WGA, and LFA; this finding suggests that they produced alpha-mannose and alpha-neuraminic acid that represented serum type glycoprotein. The positive staining of epithelial goblet cells and glandular mucous cells with PNA after neuraminidase digestion suggests that they produced mucin-type glycoproteins. The staining of the mucous blanket by WGA, LFA, SNA, RCA-I, LCA, PNA, SBA, PHA-E, and UEA suggests the presence of alpha-neuraminic acid, beta-galactose, N-acetyl alpha-galactosamine, and alpha-fucose. The epithelial cell (nonsecretory) surface was stained largely by WGA, LFA, SNA, RCA I, Con-A, and LCA; this finding suggests the presence of alpha-neuraminic acid, beta-galactose, and alpha-mannose. PMID- 1746831 TI - Afferent activity in the external branch of the superior laryngeal and recurrent laryngeal nerves. AB - We investigated the presence of respiratory-modulated receptors in the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (ExtSLN) in anesthetized, spontaneously breathing dogs. Of 39 receptors recorded from the ExtSLN, the vast majority responded with a slowly adapting discharge to compression of the cricothyroid muscle, and only 1 responded to probing of the laryngeal mucosa. Ten receptors showed a respiratory modulation. All 30 receptors recorded from the RLN responded to probing of the laryngeal lumen, most of them (60%) with a rapidly adapting response. Seven of the slowly adapting receptors exhibited a respiratory modulation; 38% of the receptors tested were stimulated by water, and only 15% by smoke. No receptors stimulated by laryngeal cooling were identified in either nerve. Our study indicates that in the RLN and the ExtSLN there are relatively few afferents responding to changes in transmural pressure and mechanical irritation, as compared to the internal branch of the SLN. The relative scarcity of receptors responding to transmural pressure and irritant stimuli is consistent with previous observations in dogs that indicate a preponderant role for afferents in the internal branch of the SLN in the reflex responses to laryngeal stimulation. PMID- 1746832 TI - Pulsatile tinnitus from a dural arteriovenous fistula. PMID- 1746833 TI - Salivary neoplasms of the jaw bones with particular reference to central mucoepidermoid carcinomas. AB - Intragnathic salivary-type neoplasms are few in number, are of debated histogenesis, and are most often classified as mucoepidermoid carcinomas. Two generating tissues have been proposed for the origin of these central (intraosseous) tumors: enclaves of salivary tissue and a metaplasia of the linings of odontogenic cysts. They are not mutually exclusive. Although most mucoepidermoid carcinomas have been low grade, these neoplasms nonetheless have a very respectable recurrence rate and can be fatal. PMID- 1746834 TI - Facial nerve and medially invasive petrous bone cholesteatomas. PMID- 1746835 TI - Further morphologic studies on collagen injected into canine vocal folds. AB - We compared the morphologic fate of three types of soluble bovine collagen injected into vocal folds of dogs: 1) Zyderm collagen implant containing 35 mg/mL of collagen (ZCI I), 2) Zyderm collagen implant containing 65 mg/mL of collagen (ZCI II), and 3) GAX collagen containing 35 mg/mL of collagen minimally cross linked with 0.0075% glutaraldehyde. Light and electron microscopy showed good host tolerance and a long-term persistence of the three types of collagen at the site of injection. The collagen implants were progressively colonized by fibroblasts and capillaries accompanied by host collagen deposition. No inflammatory process or foreign body reaction occurred, in contrast to the typical host reaction to injected Teflon. The colonization of GAX collagen was slower than for ZCI I and ZCI II. No other significant difference was evident among the three types of injectable collagen. All three appear to be very suitable materials for laryngeal implants; moreover, they seem to best meet accepted requirements for a good implant: they are easy to inject, they are well tolerated, and they persist for a long time. We prefer GAX collagen for clinical use because of its lower reactivity and higher stability, and because overinjection is not necessary (GAX shrinks less than ZCI I and ZCI II). PMID- 1746836 TI - Cochlear bone erosion: effects on cochlear hair cells. A scanning electron microscopy study. AB - Cochleae from gerbils with normal middle ears were compared with cochleae from gerbils with experimentally induced cholesteatomas that were in contact with the cochlear wall (stage III cholesteatomas). Cochleae from gerbils with stage III cholesteatomas were further divided into two groups: one without erosion of cochlear bone, and one with cholesteatoma-induced bone erosion but without cochlear fistulae. The cochleae with bone erosion showed significant loss of outer hair cells in the middle and apical turns, but not in the basal turn. The cochleae with stage III cholesteatomas but without bone erosion did not differ from normal controls. These results suggest that an ototoxic agent, involved in the process of bone erosion, acts through the bony cochlear wall. PMID- 1746837 TI - Serial culture and characterization of the chinchilla middle ear epithelium. AB - We have successfully cultured a fibroblast-free chinchilla middle ear epithelium up to the 10th passage by using conditioned medium or using irradiated 3T3 cells as feeder cells. The cultured epithelial cells assumed a polygonal shape with a cobblestone appearance, indicating tight junction formation. A small number of the cells began to show abnormal morphology, such as indistinct cell boundaries, fibroid appearance, or giant cell formation, as the passage increased, particularly after the 5th passage. These morphologically transformed cells showed positive labeling with an anticytokeratin antibody, which indicated the epithelial origin of these cells. Neither ciliated nor secretory cells were observed in the serially cultured cells. The rate of cell growth slowed after the 7th passage, and after the 11th passage the cells no longer proliferated. Even with the above limitations, these cultured cells can be used for a number of in vitro experiments. PMID- 1746838 TI - Perineural extension of squamous cell carcinoma. PMID- 1746839 TI - Stensen's duct carcinomas. AB - Stensen's duct is rarely a primary site for a salivary neoplasm (11 examples in the English-language literature from 1927 to 1984). Bereft of myoepithelium, the neoplasms are histologically malignant and have been of mucoepidermoid, squamous, or undifferentiated types. Surgical management is predicated on the location and stage of the carcinoma. PMID- 1746840 TI - Microbiology of 'normal' tonsils. PMID- 1746841 TI - Hearing gain after stapedotomy, partial platinectomy, or total stapedectomy for otosclerosis. AB - The differences in hearing gain 1 year after stapedotomy, partial platinectomy, or total stapedectomy for otosclerosis were studied separately at 0.5, 1, 2, 4, and 8 kHz with the data available from 311 consecutive primary operations performed between 1980 and 1982 in the University of Nijmegen Department of Otorhinolaryngology. Three groups of patients were matched for age, sex, clinical type of otosclerosis, and type of 0.6-mm all-Teflon piston. The hearing gain for air conduction was significantly better by an average of 7.4 dB for all frequencies combined after either stapedotomy or partial platinectomy compared to total stapedectomy. PMID- 1746842 TI - Blood flow in expanded tissue treated with an anticontractile agent. AB - The present study investigates blood flow at several stages of expansion with and without enhancement by anticontractile agents (papaverine). Twelve 1-kg guinea pigs were divided into two groups. In group 1 were six animals undergoing tissue expansion without anticontractile agents, and in group 2 were six animals treated with a saturated solution of papaverine prior to expansion. Laser-Doppler velocimetry was used to monitor the changes in blood perfusion that occurred with each expansion. Animals pretreated with papaverine (group 2) maintained higher blood flow following inflation of the expander than untreated animals (group 1). This study provides physiologic evidence of the benefits of pharmacologic enhancement of the expansion process. Agents of this type may have a future role in the prevention of ischemic complications. PMID- 1746843 TI - Utricle, saccule, and cochlear duct in relation to stapedotomy. A histologic human temporal bone study. AB - This study was performed to determine the area in which and the circumstances under which stapedotomy can be relatively safely performed. Measurements were made from central areas of the medial surface of the stapedial footplate to the utricle, the saccule, and the cochlear duct in 10 normal and 11 otosclerotic temporal bones. The mean distances to the utricle ranged from 1.9 to 2.4 mm, and those to the saccule from 1.7 to 2.1 mm. The minimal distance to the utricle was measured from the posterior (0.58 mm) and superior (0.62 mm) borders of the stapedial footplate. The minimal distances to the saccule were from the anterior (0.76, 0.86, and 1.00 mm) border of the stapedial footplate. All other measurements were of more than 1 mm. The shortest distance between the cochlear duct and the inferior border of the footplate was 0.2 mm. Statistical analysis has shown no significant differences for the mean values obtained in normal and otosclerotic temporal bones. Fathoming of the vestibule below the central and inferior thirds of the footplate surface has shown that there is no likely danger to the vestibular end organs or cochlear duct if manipulations are carried out no deeper than 1 mm below the surface. The safest place for a stapedotomy opening is in the central and inferior-central thirds of the footplate. A stapedotomy piston of 0.4 mm in diameter can be introduced relatively safely to a depth of 0.5 mm in the vestibule over the entire surface of the stapedial footplate. PMID- 1746844 TI - Orthostatic postural control in vestibular neuritis: a stabilometric analysis. AB - Posturographic data for 182 vestibular neuritis patients were recorded on a static posturographic platform (stabilometry) with the patients' eyes both open and closed. Three of the parameters studied are presented here: mean position of the center of pressure, area of the statokinesigram, and Romberg's quotient. Vestibular neuritis modifies the performance of the fine-postural system in unpredictable ways, varying with the subject. It may disturb either the mean position of the center of pressure or the integration of visual input. Sixty of the patients in this study did not use visual input to stabilize their position in relation to their surroundings. The value of stabilometry as a method for observing the integration of visual input in the control of orthostatic posture is discussed. PMID- 1746845 TI - Tullio phenomenon and postural stability: experimental study in normal subjects and patients with vertigo. AB - The effect of low-frequency sound (LFS) on postural stability was studied in 55 healthy volunteers and in 152 patients with vertigo due to different types of inner ear disease. The sound pressure levels ranged from 130 to 132 dB and were given at frequencies of 25, 50, and 63 Hz. The duration of each stimulation lasted 30 seconds. The postural responses were measured with a force platform. The LFS stimulation improved the postural stability of the healthy subjects through the alerting response. We did not observe any difference in the body sway according to whether the LFS was delivered with monaural or binaural stimulation. Twenty-six percent of the patients with Meniere's disease, 40% with chronic otitis media with vertigo, and 26% with vertigo of peripheral origin experienced significant postural instability at least at two of the three test frequencies during stimulation with LFS. The results demonstrate that in subjects with different types of inner ear disease the vestibular system starts to respond to LFS. The activation of vestibulospinal responses by LFS seems to be an expression of the Tullio phenomenon. PMID- 1746846 TI - Inexpensive cochlear implant device. AB - We have developed a cochlear implant (CI) device modified from the House/3M cochlear implant device. The cost of raw materials was about $25. We used a new and simple technique for coating the implanted coil. We modified the circuit and removed the amplitude-modulated circuit. With this modification, the device uses less electricity and fewer transistors. There are slightly more than 3,000 patients using CI devices all over the world. Millions of profoundly deaf patients are poor and cannot afford the CI device that is now commercially available. Any university with well-trained otolaryngologists and physicists or electrical engineers can perform this technique. PMID- 1746847 TI - Bone destruction mechanisms in chronic otitis media with cholesteatoma: specific production by cholesteatoma tissue in culture of bone-resorbing activity attributable to interleukin-1 alpha. AB - To clarify specific mechanisms underlying cholesteatoma-induced bone destruction, surgical specimens of middle ear inflammatory granulation tissue with or without cholesteatoma were maintained in vitro and the bone-resorbing activity in their culture supernatants was analyzed by means of calcium release from mouse calvaria. Almost the same levels of bone-resorbing activity and prostaglandin (PG) E2 were found in the supernatants of both types of tissue. By contrast, aural polyp tissue yielded hardly any such activity or PGE2. Under the influence of indomethacin, however, only tissue with cholesteatoma produced considerable bone resorption activity, whereas PGE2 production was suppressed completely. Such activity in the cholesteatoma culture supernatant was not due to contamination of endotoxin and proved to be blocked by the introduction of anti-interleukin (IL)-1 alpha antibody into the calvarial assay system. Anti-IL-1 beta antibody had no effect on such activity. Interleukin-1 alpha was detected only in cholesteatoma tissue culture supernatants by means of enzyme-linked immunosorbent assay and by bioassay. These data suggest that the bone destruction in otitis media with cholesteatoma may be attributed to IL-1 alpha in addition to PGE2. PMID- 1746848 TI - [Antibiotic therapy in pediatrics]. PMID- 1746849 TI - [Antibiotic treatment of cystic fibrosis]. AB - Lower respiratory tract superinfection is nearly constant in cystic fibrosis and has a significant impact on mortality. The three organisms which most often colonize the bronchial tree are Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The latter organism is found in 70% to 90% of older cystic fibrosis patients. P. aeruginosa infections are remarkably persistent and cause severe, extensive lung damage. Antimicrobial therapy is indicated in patients with clinical symptoms (fever, weight loss, changes in sputum and auscultation) and should be selected on the basis of cytobacteriologic studies of sputum. Oral antibiotics are usually successful in eradicating S. aureus and H. influenzae. Conversely, intravenous therapy is required in most cases of P. aeruginosa infection. Fifteen-day courses are given repeatedly, either on a routine basis every three months, or whenever new clinical symptoms develop. Antimicrobials usually fail to eradicate P. aeruginosa even when significant clinical improvement occurs. Two-drug therapy and judicious use of the various available anti-microbial agents should delay development of resistant strains, an event which is nearly inevitable as antimicrobial treatments are repeated. PMID- 1746850 TI - [Treatment of bacterial meningitis in children]. AB - The initial treatment of infantile and childhood bacterial meningitis is now well standardized, but three current aspects are discussed in this paper. Although classically, ampicillin can still be given as the initial treatment of bacterial meningitis in children, current epidemiologic data demonstrate the emergence of resistant strains of Haemophilus and Pneumococcus, and consequently use of a third-generation cephalosporin should be preferred. Concerning duration of treatment, 4 to 5 days seem adequate for meningococci and 7 days for Haemophilus influenzae and pneumococci. Lastly, the usefulness of adjunctive antiinflammatory treatment is considered. The purpose of this treatment is to lower the risk of cerebral complications and neurosensory impairment. Current data suggest that use of corticosteroids as early as possible may be helpful. Improved understanding of the pathophysiology of pediatric bacterial meningitis has led to other forms of treatment being proposed, but their value remains to be proven. PMID- 1746851 TI - [Antibiotic therapy in maternal-fetal infections]. AB - The selection of first-line antimicrobial therapy in neonates with maternofetal infection is based on probability data from epidemiologic studies of bacterial infections. Because of the high prevalence of ampicillin-resistant E. coli strains and of the lack of susceptibility of Listeria and group D streptococci to cephalosporins, combined use of two complementary drugs, such as amoxicillin and cefotaxime with an aminoglycoside, is recommended. Each dose should be increased twofold in patients with meningeal involvement. The interval between aminoglycoside doses depends on the degree of renal maturity and therefore on gestational age. Discontinuation of treatment on the third day when clinical and biologic monitoring disproves the suspected infection avoids the occurrence of untoward effects, especially on the intestinal flora. In other cases, administration of two drugs selected on the basis of bacteriologic findings is needed beyond the third day. Specific therapy is required in infrequent infections (Candida, tuberculosis, syphilis, Helicobacter). The dosage of antimicrobials with narrow therapeutic margins (vancomycin, aminoglycosides) should be adjusted on the basis of serum assays performed at four-day intervals. Duration of therapy is usually ten days but may reach 21 days in neonates with meningitis. Prevention, in the absence of specific vaccines, rests on antenatal and perinatal treatment of women at high risk for infection. Management of neonates with group B streptococcal infection is controversial; close clinical and biologic monitoring over 48 hours may allow to reduce the use of antimicrobials. PMID- 1746852 TI - [Antibiotic treatment of pharyngitis]. AB - Antimicrobial therapy of pharyngitis focuses mainly on eradicating group A streptococci and treating recurrent pharyngitis. The French strategy rests on routine treatment of all cases of childhood pharyngitis; in the United-States, rapid tests are used to identify group A streptococci in the throat before treating. Antibiotics used against group A streptococci include beta-lactams and macrolides. Among beta-lactams, the reference drug is still penicillin, e.g., penicillin V for 10 days. However, numbers of carriers with positive throat cultures for Streptococcus pyogenes seem to be growing in the United States, with a 10-20% increase over the last twenty years. Duration of therapy could be reduced from 10 to 5 days with the new oral cephalosporins but these drugs are more expensive than penicillin. Recurrent pharyngitis is caused by a variety of organisms which are often penicillinase-producers. It follows that penicillin should not be used in these cases, which require oral cephalosporins or the amoxicillin-clavulanic acid combination. Maintenance antimicrobial therapy between acute episodes should be considered. PMID- 1746853 TI - [Antibiotic treatment of acute otitis media]. AB - The strategy of antimicrobial therapy in acute otitis media rests on bacteriologic and pharmacokinetic data. Pneumococci and Haemophilus are still the two most prevalent pathogens in acute otitis media and raise problems regarding susceptibility: 25% of Haemophilus beta-strains produce beta-lactamases and 6 to 12% of pneumococci are intermediate or resistant to penicillin. Pharmacologic features required of antimicrobials used in acute otitis media include good penetration in the ear and sustained supra-MIC levels in middle ear fluid. Kinetics of drugs in the ear are still often incompletely understood. The last selection criterion is analysis of comparative trials. Available data do not point to superiority of any drug over the others. Amoxicillin should no longer be given as first-line therapy. Amoxicillin combined with clavulanic acid (Augmentin) is effective on the entire spectrum of causative organisms. Higher levels of amoxicillin may be needed (concomitant use of amoxicillin and (Augmentin). First-generation cephalosporins are effective but may prove unsuccessful in patients with large inocula. Pediazole is clinically effective although penetration of erythromycin in the ear is delayed. The new oral third generation cephalosporins are effective in infections due to beta-lactamase producing Haemophilus strains. A bacteriologic study should be performed routinely whenever otitis media occurs in an infant under three months of age. PMID- 1746854 TI - [Treatment of urinary tract infections]. AB - Urinary tract infection (UTI) is common in pediatric age groups and may cause permanent renal damage. Because UTI may occur as the first manifestation of urinary tract malformation, evaluation, of urinary tract morphology should be routine. Variables influencing selection of the most appropriate therapy include the causative organism, location of the infection to the distal and/or proximal urinary tract, severity of constitutional symptoms, age, and history for prior urologic disease. Treatment of pyelonephritis requires bactericidal antimicrobial agents capable of achieving rapid sterilization of the renal parenchyma. Animal experiments have shown that the most effective agents are third-generation cephalosporins and aminoglycosides. Antibiotics are selected on the basis of age and severity of infectious symptoms. In infants under 18 months of age and in patients with severe constitutional symptoms, parenteral administration of both a third-generation cephalosporin and an aminoglycoside is recommended. Patients above 18 months of age who are not severely ill can be given a single oral drug, e.g., a cephalosporin, amoxicillin with clavulanic acid, or cotrimoxazole. Therapy should be continued for ten days in patients with infection of the proximal urinary tract, whereas 5 to 7 days are adequate in patients with cystitis and normal urinary tract morphology. PMID- 1746855 TI - [Counseling for the prevention of HIV infections in pediatric situations]. AB - Health care professionals who are not adequately informed may have irrational attitudes when caring for HIV-infected pediatric patients. Prevention of contamination rests on thorough knowledge of high-risk pediatric groups and of potentially contaminating situations. In the delivery room and in intensive care settings, a broad set of measures for preventing contamination by blood is needed, whereas in maternity wards preventive steps are needed only during cord stump care. In pediatric departments, care should be taken to avoid injuries with sharp, blood-soiled instruments and to cover all skin lesions. HIV-infected children should be allowed to participate in group activities if they are healthy enough to do so. If an injury should occur, management includes immediate disinfection, reporting, and serial serologic testing, as well as early AZT therapy. PMID- 1746856 TI - [Bilateral newborn testicular torsions]. AB - A case of bilateral spermatic cord tension in a neonate is reported. Clinical findings are compared with those in 22 previously published cases. Obstetrical history is usually unremarkable. Torsion occurs prior to birth or immediately after birth. The two cords are involved simultaneously or successively. Edema of the scrotum is found in recent spermatic cord tension, whereas subsequently the tests are extremely hard and occasionally severely atrophied. Prognosis is poor since castration or poor testicular viability was the outcome in most cases. PMID- 1746857 TI - [A rare and little known cause of cyanosis: pulmonary arteriovenous aneurysm]. AB - Cyanosis with digital clubbing and a systolic murmur were found in a five and a half-year-old. The usual causes of cyanosis, including congenital heart disease, were discussed. Correct diagnosis was, however, arteriovenous aneurysm of the lung which was seen on the pulmonary angiogram. The lung density on chest films and lack of echocardiographic evidence of congenital heart disease might have suggested this infrequent malformation. Permanent cure was achieved by removing the lower and middle lobes of the right lung. PMID- 1746858 TI - [Arterial blood pressure in Moroccan children and adolescents]. AB - To develop blood pressure reference values for Maroccan children, a survey was carried out in 1987-88 in a group of 10,000 children 4 to 18 years of age. Study subjects were randomly selected among schoolchildren from the Great Casablanca Wilaya. There were 4,818 boys and 5,182 girls. To ensure optimal reliability of data, a precise, standardized methodology was used; blood pressure was measured in the supine position after at least five minutes rest, two cuffs of different sizes were available and selected according to age and body weight, and diastolic blood pressure was defined as Korotkow phase V. Distribution of blood pressure values was studied by age, sex and stature. Results were expressed as means +/- standard deviations and as percentiles. Blood pressure values were found to increase gradually with age, with sex-specific variations. Values were higher in post-pubertal girls. A linear positive correlation between arterial blood pressure and stature was found. This correlation was stronger than the blood pressure-age correlation. These data were compared with previous reports in the literature, although this analysis proved difficult because of variations in methods and results across studies. PMID- 1746859 TI - Why aesthetic plastic surgery became popular in Brazil. PMID- 1746860 TI - Orbicularis oris muscle: a double-breasted suture for its repair in the unilateral cleft lip. AB - The release of abnormal insertions of orbicularis oris muscle from the columella and ala base, and from their inferior attachments along the labial margin, provides muscle flaps for a double-breasted suture in cleft lip repair. Using the muscle flaps for double-breasted sutures realigns the orbicularis oris muscle fibers to achieve an anatomical and functional repair that is characterized by a symmetrical lip length, nostrils, philtral column, and philtral dimple. Double breasted sutures also increase muscle thickness surrounding the lip and consequently provides better symmetry for the nostril floor. PMID- 1746861 TI - Flankplasty: a specific treatment to improve body contouring. AB - A complete study of the flank region's unaesthetic distortions is reported. Comments regarding and illustrations of the different clinical appearances of local skin turgor and fat deposits are also noted. A classification of the different types of flank distortions, whether or not combined with similar problems of the surrounding regions, complete the study for the indication of correct treatment. Liposuction, surgery, or both, combined in the same or different stages, complete the main steps of the procedure. PMID- 1746862 TI - Subcutaneous pedicle flaps in facial repair. AB - This study shows the importance of rotating subcutaneous pedicle flaps for a wide range of possibilities in face and nose reconstruction. The method described was studied and developed over 10 years in 305 patients with basocellular carcinoma of the face. This method uses areas with natural depressions and provides good aesthetic results, which are sometimes difficult to obtain using conventional reconstruction methods. Because of their circulatory nature, subcutaneous pedicle flaps can be performed on most parts of the face. The flap can be prepared from skin where there is cellular subcutaneous soft tissue (randomized vascularization), in which the facial circulation is tangential and vertical to the skin surface (i.e., like perforating arteries). These characteristics can be found in nasogenian wrinkles, the malar region, the upper and lower lips, and the chin. The flaps can not be prepared, however, from a region corresponding to the front of the face, the cervical, or the nose, where the necessary circulatory details and soft tissue are not available. PMID- 1746863 TI - Calf augmentation. AB - I present my experience with calf augmentation surgery for improvement of the contour of so-called "thin legs" due to hypotrophy of the gastrocnemius muscles and the local skin covering. A special type of silicone-gel prosthesis is placed between the muscle and its fascia. The space is created by a specific instrument I developed to perform the dissection. The introduction of the prosthesis is done through a 3-cm transverse skin incision on the popliteal line. PMID- 1746864 TI - Extended dissection of the mental area in face-lift operations. AB - Extended dissection of the mental area has been used successfully in the last 15 years, in the routine rhytidectomy, to solve the problem of the senile mental, also called the "witch's chin." After the face and neck dissection, the chin skin is completely dissected at the same anatomical level of the face and finally molded with micropore into its new position. Ancillary procedures on the neck, face, and chin can be combined and performed in the same stage. The technique and combined procedures in the last 500 patients, from a total of 4,856 patients with rhytidectomy, are evaluated and analyzed. PMID- 1746865 TI - Omphaloplasty. AB - Two different omphaloplasty procedures are presented. The first procedure, resulting in a four-point, star-shaped navel and indicated for patients with classic abdominoplasties, aims at preventing widening of the navel, as well as stenosis, later on, postoperatively. The second procedure, based on the rotation of the remaining navel and indicated for both patients with midi or mini abdominoplasties and patients with secondary omphaloplasty, also aims at preventing stenosis and widening of the umbilical scar; however, no external scars remain after this procedure. PMID- 1746866 TI - Micrografts and minigrafts: a new approach for baldness surgery. AB - The main problem in conventional operations for baldness has certainly been the resultant scar. The scar stigmatizes the patient's forehead and frequently gives an unaesthetic and unnatural appearance. Any observer would say the patient is wearing a "hairpiece" or some other artificial element. To minimize this problem, we introduced and improved a new procedure for the treatment of pattern baldness by using microsurgical hair grafts taken from the occipital region. These are inserted, one by one, into the bald area through a small microsurgical knife and with the help of a jeweler's forceps. This technique is based on works of Marrit and Nordstrom, who made use of these micrografts for the first time to hide the anterior line of the forehead after surgery. PMID- 1746867 TI - Nasal tip treatment by lengthening of the short columella in bilateral cleft lip sequelae. AB - The mobilization of two muco-chondrocutaneous flaps obtained by two parallel incisions along the nasal dorsum may elevate and elongate the columella in patients with bilateral cleft lips. The nose tip is also modulated by a triangular tissue resection right above the alar segment in both sides. Thirty four patients have been treated with this method. PMID- 1746868 TI - Treatment of the Negroid nose without nasal alar excision: a personal technique. AB - A new procedure is used for surgery of the Negroid nose. It is based on the elevation of the columella, rebuilding the nose tip and the nostril entrance, and bialar diameter reduction, leaving no external scars. The technique requires an almost all subperiosteal undermining of the soft tissues of the mid-one-third of the facial level. This procedure is performed through the Caldwell-Luck incision. Special stitches are placed on the bialar line and the columella, narrowing the nose base to the desired dimensions. No recurrency has been observed in all the patients who underwent surgery. PMID- 1746869 TI - [Ultrasound-guided fine-needle punctures of abdominal masses: cytology or histology? Comparative prospective study]. AB - The aim of this study has been for one part to assess the obtaining of cytological and histological material from the same patients with the minimum amount of injections using a fine needle (diameter less than 1 mm) and also to evaluate the histological and cytological supply, individually and jointly in the diagnosis of abdominal tumors. Seventy lesions of which 58 hepatic have been punctured with fine needles of 20 (0.9 mm) to 22 G (0.7 mm). Material has been obtained in 98.6 per cent of cases for cytology and 54 per cent of cases for histology. Their respective sensitivity in the diagnosis of malignant tumors was 96.8 per cent and 86.8 per cent and was not improved by adjoint analysis. The specificity was 1 for cytology. The differential diagnosis in malignant hepatic tumors between hepatocarcinoma and metastasis was existent in 94.3 per cent of cases for cytology and 90 per cent for histology with no benefit coming from the association of two. In the group having hepatic metastasis without known primary cancer having found histological confirmation of the primary lesion, the cellular type has been revealed in exactitude in 94.4 per cent of cases with cytology and in 63.6 per cent with histology. No complications have been observed. The fine needle cytological aspiration ponction gives very satisfying results, comparable with regard to the diagnosis contribution to results of published studies, obtained with the use of coarse needle biopies. We suggest that fine needle ponction should be used preferentially and that coarse needle biopsy should be restricted to the few cases in which the former does not yield sufficient information. PMID- 1746870 TI - [Obstructive jaundice in Yaounde. Value of echography and transhepatic cholangiography in determining the cause]. AB - The purpose of the study was to assess the clinical value of ultrasonography (US) and percutaneous transhepatic cholangiography (PTC) in the workup of obstructive jaundice in Yaounde. From 3,000 ultrasonographic studies done between September 1987 and February 1990, the authors drew 37 cases of obstructive jaundice. 22 of them were explored with both US and PTC. The cause of obstruction was tumor for 14, inflammation or malformation for 4 and biliary stone for 4. US could predict the cause in 55 p. cent of cases and PTC in 77 p. cent of cases. PTC was particularly helpful in case of non tumoral causes. The authors conclude that, in their setting where computed tomography is scarce and expensive, the combination of both US and PTC is rewarding, when the problem is the determination of the nature of obstruction. PMID- 1746871 TI - [Mesenteric carcinoid tumor presenting as an intra-abdominal abscess]. AB - The authors describe a case of mesentery primitive carcinoid tumor presenting as an abdominal abscess. The clinical findings and the physiopathological mechanisms are discussed. PMID- 1746872 TI - [Secondary tuberculous infection of a pilonidal sinus]. AB - The authors report the case of a pilonidal sinus which was the site of active tuberculosis. They stress the rarity of this condition. Particular emphasis is placed upon the need for histopathological examination of all operative specimens resulting from excision of a perianal lesion. PMID- 1746873 TI - [Giant cystadenocarcinoma of pancreatic origin and supra-mesocolic topography]. AB - The authors report a case of pancreatic cystadenocarcinoma developed within a few days as a voluminous cyst of the left hypochondriac region, pushing away the organs of the supramesocolic zone. The tumor removal is easily performed because it was surrounded by a fibrotic capsule and their was no precise attach to the neighbouring organs. Diagnosis is carried out by microscopic examination revealing a tubulo-papillary cystadenocarcinoma of the pancreas. Quasi synchronous apparition of disseminated hepatic metastases advocates for heavy malignancy and justifies intrahepatic chemotherapy. PMID- 1746874 TI - [Crohn's disease and pregnancy]. PMID- 1746875 TI - [Helicobacter pylori gastritis: a new infectious disease. Reflections from personal experience]. AB - To determine the relationship of microscopic chronic antral gastritis to Helicobacter pylori, 69 consecutive patients were studied. In a prospective longitudinal study, at least 2 successive gastroscopies with antral biopsies were performed (177 investigations on the whole). Sixty six of the 69 patients were treated with various therapeutic regimens i.e. antiulcer drugs and/or antibiotics. The type and intensity of inflammation (as based on whole inflammatory infiltrate density, polymorphonuclear cells presence or absence and IgA and IgM plasma cells counts) were correlated with H. pylori status (Giemsa staining and/or biopsy culture). The presence of the organism (Hp) and the gastritis were significantly correlated (high grade of whole inflammatory infiltrate Hp + ve: 98/109 90 p. cent, Hp-ve: 9/61 15 p. cent, p less than 0.001- presence of neutrophil PMNC Hp + ve: 80/109 73 p. cent, Hp-ve: 1/61 2 p. cent; p less than 0.001--IgA and IgM plasma cells respectively Hp + ve: 7.6 +/- 6.6, 10.6 +/- 7.1, Hp-ve 1.9 +/- 2.9, 4.2 +/- 4.5; p less than 0.005). Clearance and/or eradication of H. pylori after antibiotic treatment were associated with the disappearance of chronic gastritis activity and a statistically significant decrease of whole inflammatory infiltrate density (p less than 0.001) and IgA (p less than 0.005) and IgM (p less than 0.01) plasma cells counts. Mucosal inflammation was unchanged in case of H. pylori persistence and inflammation worsening occurred in case of infection relapse. H. pylori gastric mucosa colonization seemed to be responsible for the antral chronic inflammation associated with its presence. This study documents that antral chronic gastritis is a microbial disease associated with infection by H. pylori, against which there is an inflammatory response characterized by a significant mucosal infiltration with granulocytes and IgA and IgM secreting plasma cells. PMID- 1746876 TI - [The history of the Zollinger-Ellison syndrome]. AB - In 1955, the concept that an ulcerogenic islet cell tumor was responsible for a marked ulcer diathesis that led to gastric hyperacidity was proposed by myself and Ellison. Recently is was suggested that this concept marked the beginning of modern gastrointestinal endocrinology. Although these pancreatic ulcerogenic tumors are relatively uncommon, a survey in 1987 stated that inquiries about the tumor were the most common references requested from surgical journals. The original diagnostic triad proposed included a fulminating ulcer diathesis (12-hr secretion 2-3 liters), rapidly recurring ulceration despite adequate medical, surgical, and radiation therapy, and identification of a non-beta islet cell tumor of the pancreas. The non-beta islet cell was considered to be different from the cells producing insulinoma, which up to that time was thought to be the only type of islet cell tumor produced by the pancreas. PMID- 1746877 TI - [Lactitol in the treatment of constipation in the adult. Open, non-comparative study of its efficacy and its clinical and biological tolerance]. AB - To study clinical and biological tolerability, 114 chronically constipated patients of both sexes, aged 18-70, without any organic alteration of the colon, received lactitol over a period of one or two months. Clinical tolerability was found to be good by 80 per cent of patients and biological tolerability excellent. Clinical efficacy was found correct for 80 per cent of patients with a dosage of 20 g (single dose in the evening). All patients, except one, agreed with the packaging and the taste of the product. PMID- 1746878 TI - Effect of mitomycin C and bromodeoxyuridine on Fanconi anemia lymphocytes. AB - The authors studied the effect of mitomycin C (MMC) and bromodeoxyuridine (BrdU) on the induction of chromosome aberrations on lymphocytes of four patients with Fanconi anemia (FA) and of one normal subject. A control culture and six experiments were designed to test the possible synergic effect of MMC and BrdU. Their results revealed no evidence of MMC-BrdU synergism on the induction of chromosome aberrations in FA lymphocytes. However, chromosomes showed more damage when FA cells were harvested 24 h after MMC stress than when cells were harvested shortly after treatment. This can be explained by a DNA repair defect or by a toxic effect of oxygenation of cells during the procedure. PMID- 1746879 TI - Pure 4p trisomy due to a de novo 4q;22p dicentric translocated chromosome karyotype 46,XX,-22,+t(4;22)(q1200;p13). AB - A de novo t(4;22)(q1200;p13) is reported in a girl with a florid 4p trisomy phenotype. The abnormal chromosome was identified by high resolution, C-bands and confirmed by 5-BrdU as de novo dicentric translocated chromosome. PMID- 1746880 TI - Segregation analysis of autosomal fragile sites in three families with the fragile X chromosome. AB - Fragile sites on chromosomes 9, at 9p21, 10, at 10q25 and 12, at 12q24, were found in the lymphocytes of some members of three families during the study for detection of a fragile X chromosome. The sites were found to be heritable and folato-sensitive. The genetic implications of these results are discussed. PMID- 1746881 TI - Four cases of trisomy 9p syndrome with particular chromosome rearrangements. AB - The authors present four children, two males and two females, with a 9p duplication, derived from various chromosome rearrangements, diagnosed using clinical, cytogenetic and biochemical evaluations. In particular, GALT dosage allowed them to define with accuracy the different chromosome break-points. PMID- 1746882 TI - Assessment of X bends in patients with atypical X chromosome phenotypes. AB - Several patients with X chromosome structural abnormalities have been more severely affected clinically than expected. Since bends at Xq13-21 have been associated with inactivation, the authors scored bends retrospectively in 62 patients with X chromosome aneuploidy and 21 cases with structural abnormalities of the X chromosome. They found that patients with 2 X inactivation sites where one X was structurally abnormal had significantly fewer cells with X bends than normal 46,XX. In addition, these patients also showed X bends on the normal X more often than would be expected if non-random X inactivation of the abnormal X chromosome was occurring. Five of the 6 patients with a short or long arm deletion or paracentric inversion of Xq were mentally retarded or had other congenital anomalies not usually associated with Turner syndrome. This suggests to them that these clinical findings may be related to interference with X inactivation patterns in cells with a structurally abnormal X chromosome. PMID- 1746883 TI - Slide Flask direct amniotic fluid cultures. AB - Slide Flask direct amniotic fluid culture enabling: to decrease the risk of abnormalities caused by the technique itself, to facilitate laboratory work, to shorten culture time (8 to 13 days). PMID- 1746884 TI - Prune-belly anomaly and large interstitial deletion of the long arm of chromosome 6. PMID- 1746885 TI - [Two novel reciprocal translocations involving chromosome 6 in the domestic pig]. AB - In the present study 2 new reciprocal translocations are described in two hypoprolific boars. The first one, a Gascon/Meishan boar, has produced a mean value of 7.37 +/- 0.69 piglets, vs 12.41 +/- 0.22 piglets per litter in contemporaries. The second one, a Pietrain/Large-White boar, has produced a mean of 5.42 +/- 0.69 vs 12.41 +/- 0.22 piglets per litter in contemporaries. Each of these animals carries a new chromosome translocation involving chromosomes 6, 8 and 15, respectively. The first translocation seems to be a de novo occurring abnormality. The economic consequences of these abnormalities are discussed. Carrier of the gene HAL, the abnormal chromosomes 6 involved in these translocations are important, and could useful markers in gene mapping and flow cytometry studies in pigs. PMID- 1746886 TI - [Frequency and distribution of aneuploidy in human gametes: differences as a function of sex]. AB - The frequency and the distribution of aneuploidies were analysed in both spermatozoa and mature oocyte. The present study has pooled 13,975 human sperm chromosome complements and 1,897 oocyte chromosome complements examined to date. The overall frequency of aneuploidy is 10% in spermatozoa and 22.4% in oocytes. Human sperm is characterized by a significant excess of hypo-haploidies and an equitable distribution of aneuploidies among all chromosome groups, whereas mature oocytes display an equal ratio of hypo-haploidies: hyper-haploidies and a high variability in the distribution of non-disjunctions; in the A, B, C and especially in D and G groups, there is a significant difference between the observed and estimated rates of non-disjunction and the frequencies expected from an equal partitioning of non-disjunctions among all chromosomes. This indicates that non-disjunction is not a random event in female meiosis, and consequently that there are differences in the meiotic process between the sexes. PMID- 1746887 TI - Routine autoradiographic analysis of DNA excision-repair. Report of prenatal and postnatal diagnosis in eleven families. AB - DNA excision-repair of UV induced damages was investigated by unscheduled DNA synthesis and quantitative autoradiography. The method has been routinely used on lymphocytes for postnatal diagnosis of xeroderma pigmentosum and PIBIDS syndrome. Ten XP-families including 13 clinical XP patients and 9 XP-risk children, and one family with one clinical PIBIDS case and one PIBIDS-risk child were screened. Each of the 14 affected patients were biologically ascertained with a significant excision-repair defect. Among the 9 XP-risk children without clinical manifestations, the DNA excision-repair was defected in 4 cases considered as biological XP, and normal in 5 cases considered as biologically normal subjects. Likewise the PIBIDS-risk child exhibited a normal excision-repair. According to the age of the XP or PIBIDS-risk children, and the delay of appearance of clinical manifestations, the method should not present neither false positive nor false negative results and allows the infraclinical diagnosis. The protocol was extended for prenatal diagnosis on amniocytes and fetal cord blood. Excision repair analysis on normal cultivated chorionic villi cells has been performed allowing a further first trimester prenatal diagnosis. PMID- 1746888 TI - Lethal progeroid syndrome with osteolysis. Case report. AB - A particular progeroid syndrome with severe acro-osteolysis, cutaneous changes, failure to thrive, and early death is described in a young boy. Progeria and mandibulo-acral dysplasia are discussed, but early death is unusual in these two syndromes. This observation raises the question of a large spectrum including all of these syndromes. PMID- 1746889 TI - Interstitial deletion of 16(q13q22) in a newborn resulting from a paternal insertional translocation. AB - A dysmorphic newborn showed an interstitial deletion of the long arm of a chromosome 16 due to a balanced paternal insertional translocation 46,XY,ins(14;16)(q23;q13q22). The insertion was confirmed by chromosomal in situ suppression (CISS-) hybridization. Clinical features considered to be typical for a 16q- phenotype are demonstrated in this patient. Similar observations described in the literature are compared and discussed with reference to the phenocritical region. PMID- 1746890 TI - Ring chromosome 8 associated with microcephaly. AB - A two-year-old mental defective girl with microcephaly and minor dysmorphic features had a 46,XX,r(8) karyotype. Low birth weight, short stature, and mental retardation were common features in the four known patients with r(8). PMID- 1746891 TI - Ring chromosome 14 syndrome. Report of two cases, including extended evaluation of a previously reported patient and review. AB - A case of r(14) chromosome is described and new information is added to a previously reported patient. The r(14) syndrome is reviewed on the basis of 37 known patients. The major features include prenatal and postnatal growth retardation, mental retardation, seizures, microcephaly, and distinct facial dysmorphism, including elongated face, narrow palpebral fissures, epicanthus, and broad nasal bridge. Other characteristic anomalies found only in some patients are retinal anomalies, lymphoedema of hands and feet, and prones to pulmonary infections. PMID- 1746892 TI - Pericentric inversion of the X chromosome: presentation of a case and review of the literature. AB - A large pericentric inversion of the X chromosome [inv(X)(p22.31q26.3)] was found to be transmitted in four generations through phenotypically normal males and females. In one female carrier, the inv(X) was late replicating in 70% of lymphocytes and 46% of skin fibroblasts. Steroid sulfatase (STS), an enzyme which normally escapes inactivation has been located to Xp22.32 and, in our case, has been moved to an aberrant position. We have assayed its activity in clones with the inv(X) inactive or the normal X inactive and found no significant differences. Thus, the STS locus escaped X inactivation in both the normal and the inverted X chromosomes. A review of the literature shows that almost half of the breakpoints on the short arm are found at region p22 and we propose that low copy repetitive DNA segments along the X chromosome are responsible for non homologous pairing and production of inversions. PMID- 1746893 TI - A peptide from the GAP-binding domain of the ras-p21 protein and azatyrosine block ras-induced maturation of Xenopus oocytes. AB - The ras-oncogene-encoded p21 protein causes malignant transformation of NIH 3T3 cells and maturation of Xenopus oocytes when microinjected into these cells. P21 is known to interact with GTPase activating protein (GAP) intracellularly. Residues 32-45 of p21 have been implicated in interacting with GAP. In a previous study, we demonstrated that a synthetic peptide containing residues 35-47 from the GAP-binding region of p21 could block in vivo the effects of oncogenic p21 protein. It has also been found that an antibiotic, azatyrosine, blocks ras initiated cell transformation. We now demonstrate that both of these agents inhibit the ras-p21 protein-induced maturation of Xenopus oocytes in a dose related manner when microinjected into oocytes. The effects of each of these agents is specific. Both agents block insulin-induced maturation of oocytes, a process which is known to involve activation of endogenous normal p21 protein. On the other hand, neither agent inhibited oocyte maturation induced by progesterone, which is known to initiate oocyte maturation by ras-independent pathways. The inhibitory effects of the peptide were not mimicked by a control peptide from the CD4 receptor protein. Furthermore, the effect of azatyrosine was not mimicked by L-tyrosine. These results suggest that both the peptide and azatyrosine have potent anti-ras effects intracellularly. PMID- 1746894 TI - Distribution, DNA damage and cytotoxic effects of etoposide in human tumor xenografts in vivo. AB - Mechanisms of resistance to VP-16 in vivo were studied using sensitive and multidrug resistant human breast tumor (MCF-7) cells, implanted bilaterally in nude mice. Administration of VP-16 (40 mg/kg, i.p.) indicated that there were no significant differences in either accumulation and retention of VP-16 or in the drug-induced bulk DNA damage in sensitive or resistant solid xenografts. Furthermore, under these conditions, no differential cytotoxic response to VP-16 was observed in solid tumors. PMID- 1746895 TI - Clinical evaluation of the new tumor marker TAG-72. AB - Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.) carcinoma. Moreover, the measurement of TAG-72 may also be clinically useful in discriminating malignant from benign effusions. Serum TAG 72 and CEA levels were evaluated longitudinally in a series of patients following resection of primary G.I. carcinomas. A consistent relationship between efficacy of the surgery and serum TAG-72 clearance was observed, and TAG-72 alone or in combination with CEA accurately predicted recurrence of malignant disease in greater than 90% of the patients. The results indicate that TAG-72 is a new human serum tumor marker which, measured alone or in combination with other well established markers, may improve the diagnosis and/or clinical management of malignant disease. PMID- 1746896 TI - Hypoxia and acidity increase the cytotoxicity of mitomycin C and carboquone to human tumor cells in vitro. AB - To clarify the influence of hypoxic and acidic environments on the cytotoxicity of mitomycin C (MMC) and carboquone (CQ), the cytotoxicity was assessed based on decreases in intracellular ATP levels of HeLa cells exposed to the drugs at various acidic pH (pH 5.8-6.8) and low oxygen tension (5% and 0% O2) in vitro. Hypoxia and acidity individually increased the cytotoxicity of MMC, although hypoxia no longer increased it under acidic conditions. On the other hand, the cytotoxicity of CQ was enhanced in the presence of hypoxic and acidic conditions, and even more so with their combination. We conclude that acidity is a determining factor and excels hypoxia in influencing the cytotoxicity of MMC and that these two factors act synergistically on CQ. PMID- 1746897 TI - The initial steps of tumor progression in melanocytic lineage: a histochemical approach. AB - Antigen expression was studied by immunohistochemistry in 133 human melanocytic skin lesions to gain insight into the initial steps of tumor development, i.e. in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma associated antigens (HMB-45, NKI/C3, MA-930, LS59), (iii) proliferation associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression associated antigens (HLA-DR, ICAM-1), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular")nevi. A dramatic shift of antigen expression (antigen types [i] to [v]) was noted in benign nevi compared with melanocytes. Nevi with cellular atypia disclosed a tendency towards an increased percentage of tumor cells reactive for melanoma- and progression-related antigens (types [ii] and [iv]). However, there was no clear cut level of distinction of antigen expression (types [i] to [v]) between benign and primary malignant melanocytic tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression. PMID- 1746898 TI - p53 expression in cytologic specimens from benign and malignant breast lesions. AB - This study was undertaken to determine the expression of p53 gene in cytologic specimens from benign and malignant breast lesions. To detect p53 an immunocytochemical assay with p53 (pAb421) monoclonal antibody was used. Abnormalities in p53 expression were found in 19 out of 40 Fine Needle Aspiration (FNA) smears with infiltrating ductal breast carcinomas. Benign epithelial breast cells obtained from fibroadenomas, fibrocystic disease and smears from nipple discharge reacted negatively for p53 in 38 out of 39 cases. Moderate positive reaction, confined to a few clusters of epithelial cells, was observed in one smear of fibroadenoma with cellularity. The results recorded in this study show that no significant association was found between p53 staining and stage of disease, tumor size or nodal status and that the immunocytochemical assay represents a simple method for the detection of p53 associated proteins in breast lesions. PMID- 1746899 TI - A monoclonal antibody which discriminates between sub-types of astrocytoma. AB - A monoclonal antibody, M2, was produced by somatic cell hybridisation of splenocytes, from mice immunised with human fetal brain, with the murine myeloma cell line NS-1. Indirect immuno-peroxidase staining of formalin-fixed, paraffin embedded tissue sections showed that, whilst the monoclonal antibody gave a positive reaction with 32/39 astrocytomas from adult patients and 33/36 of children's astrocytomas of the adult histological type, only 17/39 of juvenile astrocytomas were stained. A Chi-squared test showed that the difference in staining between the two groups (adult versus juvenile) was highly significant (p less than 0.0001). In contrast, using a polyclonal antiserum to GFAP, a significantly larger proportion of juvenile astrocytomas than adult astrocytomas stained positively (p less than 0.05). Thus, whereas the distribution of GFAP accorded with the general finding that the degree of malignancy of a tumour correlates with the loss of cell type specific markers, the distribution of M2 reactivity was similar to that of some oncogene products which increase with malignancy. From the flow cytometry data it is apparent that the antigen recognised by M2 is not cell cycle dependent. PMID- 1746900 TI - Implication of the ras and myc oncoproteins in the pathogenesis of mycosis fungoides. AB - In the present work, we studied the expression of the c-myc oncoprotein p-62 and the ras oncoprotein p-21 in the dermal cellular infiltrate of paraffin embedded skin specimens, obtained from patients suffering from Mycosis Fungoides and Sezary syndrome. Nineteen specimens from early stage Mycosis Fungoides, nineteen from advanced stage Mycosis Fungoides and four from Sezary syndrome were included in the study. The oncoprotein detection was achieved immunohistochemically, using the mouse monoclonal antibody myc 1-9E10 and the rat monoclonal antibody Y13-259 for p-62 and p-21 respectively. Increased detection of both p-62 and p-21 in atypic lymphoid cells was shown in advanced stages of Mycosis Fungoides (third stage plaques and tumors) as compared to early stages (premycotic erythema, second stage plaques). In advanced stages, however, the percentage of P-62+ atypic cells proved to be higher than that of p-21+ atypic lymphoid cells. The implication of increased p-62 and p-21 oncoprotein expression in the process of lymphomagenesis in cutaneous T-cell lymphomas is discussed. PMID- 1746901 TI - Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer. AB - The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined. PMID- 1746902 TI - Characterization of multiple cathepsin B mRNAs in murine B16a melanoma. AB - We have previously shown that the highly metastatic murine B16a melanoma expresses a high level of cathepsin B mRNA which is associated with three transcripts of 2.2, 4.0 and 5.0 kb, while in contrast only a single 2.2 kb cathepsin B RNA was detected in normal murine tissues. Using recombinant DNA techniques, cDNAs corresponding to these three transcripts have been isolated from a B16a melanoma cDNA library. Sequence analysis indicates that all three mRNA transcripts contain identical coding sequences for normal preprocathepsin B. However, the 4.0 and 5.0 kb transcripts contain unusually long extended 3' untranslated regions. These results suggest that the post-transcriptional processing pathway of the cathepsin B gene is modified in B16 melanomas. The results also indicate that the increased extracellular secretion of larger forms of cathepsin B by tumors is most likely due to post-translational mechanisms and does not involve alternative splicing or a coding mutation in the gene. PMID- 1746903 TI - Cancer growth and progression in the framework of comparative oncology. A new approach to cancer therapy. AB - The influence of comparative oncology is most timely in view of the fact that there are significant intra- and interspecies differences in tumor development, tumor behavior and tumor reaction to various types of treatment, chemotherapy, radiotherapy, immunotherapy and multimodality-therapy. A comparison of the diverse processes which occur under normal, physiological, neoplastic and therapeutic conditions will result in a clearer understanding of tumor growth and progression. Similarly, it can be applied for selection of suitable treatment by enriching our knowledge about the progression of neoplastic diseases. Such a course will also enhance a general acceptance of the value of comparative oncology. PMID- 1746904 TI - Effects of gossypol on the cell cycle phases in T-47D human breast cancer cells. AB - Since gossypol, a naturally occurring component of cottonseed oil, exhibits a broad spectrum of activities, we have examined it as an antitumor agent on breast cancer. The effects of different concentrations of gossypol on the T-47D human breast cancer cell cycle phases were studied using cytometric image processing on Feulgen stained nuclei. The proportion of cells at different cell cycle phases was determined by discriminate analysis of the image parameters and gave good classification ranging from 86 to 100%. Gossypol was found to increase the G0/G1 fraction of the T-47D cells. This cell kinetic alteration by gossypol was shown to be dose dependent and reversible. Complete reversal of the effect of gossypol was observed after four days with a simple change to gossypol-free medium. The cells then progressed into S and G2/M phase, thus indicating that gossypol treated cells remain viable. Gossypol was shown to have a strong inhibitory effect on cellular proliferation in T-47D cells. It was also found that this agent is only toxic to cells at the highest dose tested (10 microM). The results of this study may be of clinical significance in the treatment of breast cancer, since gossypol shows strong antiproliferative properties. PMID- 1746905 TI - Chromosome and oncogene studies in human rectal and colon carcinomas. AB - Cytogenetic examinations of 48 rectal and 17 colon carcinomas and analyses of proto-oncogene activation on 67 of the former and 8 of the latter tumors were performed. Besides a general considerable heterogeneity of chromosome counts, some chromosomes were found to contribute non-randomly to hypersomies (# 2, 3, 7, 9, 19, 20 and 6) and to hyposomies (# 14, 15, Y, 21, and 18) in this material. Chromosomal markers non-randomly involved breakpoint clusters on 17p11, 13q11, 7p, 1p11, and 1p36 and on the centromeric regions of chromosomes 1, 8, 14, 15 and 21. Cytogenetic equivalents of gene amplification ("double minutes") were present in only rather small cell fractions (less than 20%) of 50% of the studied tumors. Using a cDNA technique and a battery of respective probes, proto-oncogene overexpression was screened for in the tumor samples, but also in 24 samples of inconspicuous mucosae of tumor patients and in two mucosae of healthy individuals. Simultaneous overexpression of several proto-oncogenes was the most characteristic finding in the tumor cells. However several of the mucosa samples obtained from tumor patients also just exhibited clear signals of proto-oncogene overexpression, which were not found in epithelial cells from non-tumor patients. PMID- 1746906 TI - Loss of heterozygosity at selective sites on chromosomes 13 and 17 in human breast carcinoma. AB - Four chromosomal regions were tested for loss of constitutional heterozygosity in primary tumours from 85 Icelandic breast cancer patients. Loss of heterozygosity and other types of gene rearrangements were observed in 37% of informative cases at the retinoblastoma locus, RB1, on chromosome 13q. Allele losses on chromosome 17 were tested with two polymorphic probes on 17p and two on 17q. Loss of heterozygosity or other types of genetic rearrangement were detected in 43.5% of cases on 17p near the p53 gene and 40.5% on 17q. In our study abnormalities at the RB1 locus and on chromosome 17 frequently occurred together, indicating that the coincident inactivation of more than one tumour suppressor gene may, in some cases, play a part in tumour formation. No significant correlation was found between these losses and clinico-histological parameters. Family history of breast cancer was found to be more common among patients with RB1 deletions and this trend was strengthened in cases where there were deletions at both the RB1 locus and on chromosome 17. PMID- 1746907 TI - Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leucocyte migration inhibition test in breast cancer patients. AB - To date, the results concerning the prognostic importance of parameters of cell mediated immunity in breast cancer patients are very contradictory; moreover, in most of them the results are hardly comparable due to methodological differences and heterogeneous groups of patients. In 123 patients with nonmetastatic breast carcinoma TNF alpha, INF alpha, IL 2 and reactivity in the leucocyte migration inhibition test (LMI-Test) against autologous tumor tissue were determined and the results correlated with the clinical course of the disease up to a maximum of 108 months. In breast cancer patients TNF alpha-serum levels were significantly (p less than 0.05) elevated compared to healthy controls. We also found that patients with progressive disease had higher levels than patients without recurrences. There were no differences concerning the IL-2 and IFN alpha serum levels between cancer patients and controls, nor did we find a correlation with the clinical course of the disease. In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI test. There was no difference concerning the LMI-reactivity between the groups of lymph-node negative and positive patients, but the observation that those patients with an unfavourable clinical course respond more frequently with an enhanced macrophage migration and rarely with migration inhibition was considered of notable prognostic significance. According to these results, it is possible that determination of TNF alpha and delayed type hypersensitivity reaction against tumor tissue in the LMI-test is of clinical value for the determination of risk groups. PMID- 1746908 TI - Cremophor EL inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein phosphorylation in human myeloblastic leukemia ML-1 cells. AB - Cremophor EL, a polyloxyethylene castor oil derivative used clinically as a parenteral vehicle, inhibits protein kinase c activity in vitro. The tumor promoting agent TPA (12-0-tetradecanoylphorbol-13-acetate) activated protein kinase C and induced phosphorylation of cellular proteins of human myeloblastic leukemia ML-1 cells. Polypeptides of 56 KDa, 44 KDa, 37 KDa, 35 KDa and 31 KDa were particularly phosphorylated in response to TPA activation. However, the phosphorylations of these polypeptides, especially that of 37 KDa, were greatly reduced by treatment of the TPA-activated ML-1 cells with Cremophor EL. Cremophor EL also inhibited the growth of ML-1 cells. On the other hand, the TPA-induced cell differentiation in ML-1, which is considered a separate event from protein kinase C activation, was not affected by Cremophor EL. These studies suggest biological implications for the observed in vitro activity of Cremophor EL. The studies may also provide a mechanism for the Cremophor EL-associated cytotoxicities observed when it is used clinically as a parenteral vehicle. PMID- 1746909 TI - Expression analysis of EGF-R and TGFa in human ovarian carcinomas. AB - Differences in the tumor biology of ovarian carcinomas probably influence operability and response to chemotherapy which are the most relevant prognostic factors. The phenotype of different malignant epithelial tumors including ovarian carcinomas is obviously associated with an activation of the EGF/TGFa signal pathway. When we analysed the expression of EGF-R and TGFa with biochemical, molecular-chemical and immunohistochemical methods in 29 different ovarian carcinomas, we found a correlation between the mRNA and protein levels of EGF-R as well as TGFa for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGFa expression by the tumors. The EGF-R binding ligand TGFa is produced by the tumor cells; stromal cells are TGFa negative as shown by immunohistochemistry. By the use of an immunostaining index the TGFa protein concentration was measured semiquantitatively, classifying tumors according to their TGFa production rate. The comparison of TGFa mRNA amounts and staining index supports the hypothesis that TGFa is modified posttranslationally. EGF-R or TGFa expressing ovarian carcinomas had a high response rate to chemotherapy, whereas the EGF-R or TGFa negative tumors mostly exhibit a no change or progressive disease behaviour. These findings are the basis for our assumption that ovarian carcinomas with the basis for our assumption that ovarian carcinomas with an activated EGF-TGFa system are tumor biologically different compared to the EGF-R/TGFa negative tumors. PMID- 1746910 TI - Induction of tumor degeneration by sodium benzylideneascorbate. AB - Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4 dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts. PMID- 1746911 TI - Dipyridamole potentiates adriamycin cytotoxicity by a mechanism other than inhibiting nucleoside uptake. AB - Nitrobenzylthioinosine (NBTI) and dipyridamole (DP) are competitive inhibitors of cellular nucleoside uptake. Although combined treatment of HeLa cells with adriamycin (ADM) and DP enhanced ADM cytotoxicity in cell growth and clonogenic assays, the combination of ADM and noncytostatic levels (less than 1 microM) of NBTI did not change the cytotoxic potential of ADM in vitro. DP enhanced the inhibition of clonogenicity by ADM, even in nucleoside-enriched mediums. These results suggest that the synergy between ADM and DP was hardly due to the inhibition of nucleoside uptake by DP, but was due to the enhancement of intracellular ADM accumulation by DP. PMID- 1746912 TI - Cepharanthine potentiates the antitumor effect of methylglyoxal bis (cyclopentylamidinohydrazone) on human leukemia cells. AB - Antiproliferative effects of cepharanthine, a biscoclaurine alkaloid, in combination with methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhibitor for polyamine biosynthesis, were investigated. The antitumor activity of MGBCP on human leukemic cells was potentiated by cepharanthine. Cellular polyamine levels in the leukemic cells treated with both MGBCP and cepharanthine were much lower than those of the cells treated with MGBCP alone. On the contrary, the cellular MGBCP concentration was much higher in the cepharanthine treated leukemic cells. Thus cepharanthine was considered to enhance the incorporation of MGBCP into the leukemic cells. The combination of MGBCP and cepharanthine resulted in a greater suppression of macromolecule synthesis in the cells that might have caused the greater suppression of tumor cell growth. PMID- 1746913 TI - Efficacy of pentoxifylline as a modulator of alkylating agent activity in vitro and in vivo. AB - Pentoxifylline, a methylxanthine that is used to treat veno-occlusive disease, can increase perfusion in undervascularized tissues. Addition of high concentrations, like caffeine, causes progression through radiation or drug induced G2 phase blocks, thereby limiting time for repair of DNA breaks and crosslinks. We have examined the potential of pentoxifylline to augment the effects of antitumor alkylating agents in vitro and in vivo. In MCF-7 human breast cancer cells in vitro, pentoxifylline (2 mM) present for 24 h was only slightly cytotoxic (approximately 10% cell kill at 2 mM), but when present prior to and during AA it increased the cytotoxicity of CDDP by 2 logs at 250 microM. With L-PAM in vitro, pentoxifylline was much less effective and only at a concentration of 250 microM L-PAM did 2 mM pentoxifylline increase cytotoxicity (approximately 0.3 logs). In the FSaIIC murine fibrosarcoma system, 100 mg/kg of pentoxifylline i.p. immediately prior to the alkylating agent or 50 mg/kg x 5 of pentoxifylline over 24 h with the alkylating agent given immediately after the third dose increased the tumor cell kill achieved by CDDP, carboplatin, cyclophosphamide, and thiotepa. The increase in tumor cell killing was modest (2.9-fold). Pentoxifylline in the multiple dose regimen (50 mg/kg x 5 over 24 h) was more effective than in the single dose (100 mg/kg) protocol. In the EMT6 mouse mammary adenocarcinoma, pentoxifylline (100 mg/kg daily x 5) improved the tumor growth delay produced by CDDP (3.3 mg/kg alternate days x 3), carboplatin (25 mg/kg daily x 5), cyclophosphamide (100 mg/kg alternate days x 3) and thiotepa 5 mg/kg (daily x 5). Only with cyclophosphamide, however, did the interaction appear to be large, as a 2.4-fold increase was observed. PMID- 1746914 TI - Control of the growth of leukemic cells (L1210) through manipulation of trace metals. AB - Trace metals have a role in the activity of the enzyme ribonucleotide reductase (RR) which is essential for the synthesis of DNA and the growth of lymphocytes. Manipulation of the intracellular metals of leukemic cells has been proposed for the therapeutic control of cell growth. We studied the effects of prolonged metal deprivation (Fe, Cu, Zn) on cell growth and RR activity of murine leukemic lymphocytes in culture in metal-depleted media. Intracellular metals, cell growth and RR activity were decreased in related and interdependent ways. A metal chelator (deferoxamine, DFX) had similar effect. In all cases these effects were reversible by metal supplementation. We conclude that it is possible to control RR activity and growth of leukemic cells in vitro by exposing them to a metal poor environment (eg. through the action of a chelator). These effects are not permanent, but might be beneficial if integrated with more conventional measures (chemotherapy). PMID- 1746915 TI - Monoclonal antibody characterization of sarcoma-associated antigen p102. AB - A membrane protein of Mr 102,000 Da (p102) was detected in 51 out of 53 human sarcomas, using a murine IgG1 monoclonal antibody 23-26. Antigen expression in sarcoma histologic subtypes appeared dependent on the amount of fibrous tissue matrix present in the original specimen. High levels of p102 antigen were also found in all sarcoma, carcinoma cell lines and neonatal skin fibroblasts tested. Low levels of p102 were also expressed in membranes from some specimens of melanoma, lung and colorectal carcinoma, first trimester fetus, fat, lung and liver while skin specimens expressed slightly higher levels of antigen. Lectin affinity absorption indicated p102 was mannose containing glycoprotein, isoelectric point (pI) 4.7 and affinity constant of 2.3 x 10(9) M-1, with 5.9 x 10(5) binding sites per cultured human HT-1080 fibrosarcoma cell. The overexpression of p102 in sarcomas and other neoplastic tissues suggests that this protein may be associated with the neoplastic state. PMID- 1746916 TI - Effects of various growth factors on growth of a cloned human esophageal squamous cancer cell line in a protein-free medium. AB - In order to investigate molecular mechanisms of the growth of human esophageal cancer in relation to growth factors, we have recently established a protein-free culture system [Ham's F-12: Eagle's minimum essential medium (1:1, v/v)] of TE-3 OS cells (a cloned cell line from human esophageal squamous cancer, TE-3). In the present study, we first examined effects of exogenous growth factors on the growth of TE-3-OS cells. The growth of TE-3-OS cells in the protein-free medium was significantly stimulated by insulin and insulin-like growth factor (IGF)-I or IGF-II, and less effectively stimulated by epidermal growth factor (EGF) or transforming growth factor (TGF)-alpha; platelet-derived growth factor, TFG-beta, acidic fibroblast growth factor (FGF) or basic FGF had no effects. TE-3-OS cells contained specific IGF-I binding sites (110,000 sites/cell), with a Kd value of 800 pM. Moreover, the growth induced by IGF-I, IGF-II or insulin was markedly and similarly (70-80%) inhibited by anti-IGF-I receptor antibody IgG. These data suggest that IGF-I, IGF-II and insulin, as well as EGF and TGF-alpha, are important mitogens for human esophageal cancer cells and that effects of IGFs and insulin are mediated predominantly via IGF-I receptors. PMID- 1746917 TI - Relationship of the epidermal growth factor-receptor to the growth fraction (Ki 67 antibody) and the flow cytometric S-phase as cell kinetics parameters, in human mammary carcinomas. AB - Epidermal growth factor (EGF) has been shown to have a mitogenic effect on some breast cancer cells lines in vitro. The growth of the subclass of human breast tumors which expresses the specific receptor for EGF seems to be mediated by autocrine mechanisms rather than steroid hormones. The expression of EGF receptor, as detected by an immunocytochemical method, was compared with the Growth Fraction (GF) by the Ki-67 monoclonal antibody and the S-phase content as tumor proliferative activity indexes, and with DNA ploidy and some pathologic features in 86 stage I-II breast carcinomas. Overall 52 out of 86 (60%) of the tumors were EGF-receptor positive. There was no correlation between the cell kinetics parameters and the EGF-receptor status, suggesting that its expression may be unrelated to the proliferative activity of the tumor in these clinical stages and that the EGF-receptor GF and S-phase may be independent variables in breast cancer. In our series 57% of tumors were DNA aneuploid and only a trend was found towards EGF-receptor positivity (P = 0.08). There was no correlation between EGF-receptor expression and grading or node-status. The overall picture is that of an independent relationship between EGF-receptor with the cell kinetics parameters and ploidy, confirming the complex and heterogeneous biology of breast carcinoma. These results suggest the possibility of better recognition of subsets of patients with diverse tumor aggressiveness, combining together EGF receptor status, cell kinetics and ploidy, with a better stratification for treatment options. PMID- 1746918 TI - Induction of c-myc oncoprotein and of cellular proliferation by radiation in normal human urothelial cultures. AB - Normal urothelial cultures were established from transplant ureters and irradiated or exposed to nitrosamines. The cells which survived the treatment were monitored for expression of c-myc oncoprotein. The cultures were also exposed to tritiated thymidine (3HTdR) to determine the total number of cells synthesizing DNA. The area of explant outgrowth was also measured. Proliferation is considered to be a fundamental precondition which has to be present before malignant change can take place or which has to accompany this change. The results indicate that the overall growth rate of the carcinogen-treated cultures is relatively faster than that of the controls. This is particularly true one to two weeks after carcinogen exposure. Certain areas of the culture develop abnormally, cells are different in size and shape to the normal uroepithelial cell and have the capacity to pile up and form characteristic foci. These foci continue to proliferate after senescence of control cultures and after senescence of normal areas of treated cultures. The cells in these foci express high levels of c-Myc oncoprotein. Control and treated but normal cells are negative for this antigen under the conditions used. N-ethyl nitrosamine (NEN) (0.005-0.05 micrograms/ml) and radiation (2.5-10.0 Gy) are both able to induce the changes described. The results suggest that radiation and/or nitrosamine treatment can induce uroepithelial cells to divide at a faster rate than usual. Certain cells within this fast growing culture attain the capacity to pile up and acquire a different morphology. These cells do not senescence at the usual time and are c myc positive. They may represent a subpopulation which has undergone some pre or early malignant changes. PMID- 1746919 TI - A feasibility study of cisplatin administration with low-volume hydration and glutathione protection in the treatment of ovarian carcinoma. AB - Glutathione (GSH) is a sulfur-containing nucleophile that protects against cisplatin-induced renal toxicity without reducing the antitumor activity of the cytotoxic agent. To document further the clinical role of GSH in improving the outcome of cisplatin-containing regimens, the feasibility of the GSH/cisplatin combination using a low-volume hydration protocol was evaluated in untreated ovarian cancer patients. Twelve patients at stage III (minimal residual disease) and 23 with localized disease at high risk for recurrence were treated with cisplatin (90 mg/m2, i.v. in 250 ml of normal saline over 30 min) and cyclophosphamide (600 mg/m2 i.v.) every 3 weeks. GSH (5 g in 200 ml of normal saline) was administered by a short-term infusion (15 min) prior to cisplatin. The hydration protocol consisted of 1 liter of fluids without diuretics. The treatment was well tolerated; no nephrotoxic or neurotoxic manifestations were observed. The renal excretion of cisplatin (23%) at 24 hours following infusion was lower than expected using a standard i.v. hydration protocol. No reduction of renal elimination of cisplatin could be detected in subsequent courses, thus suggesting a minimal degree of impairment in renal function. In the series of evaluable patients (11) with stage III disease, 9 had complete pathological response. In the series of patients with no clinically detectable disease initially, all were disease-free at treatment completion. Taken together with previous observations, these results support the view that the use of GSH is a successful approach in the attempt to optimize cisplatin treatment, providing a new modality of drug administration for out-patient treatment. PMID- 1746920 TI - Conservative surgery and irradiation (QUART) in the treatment of 243 stage I-II breast cancer patients. AB - From 1980 to 1987, 243 evaluable patients with pT1, pT2 (less than 3 centimeters in diameter), N0, M0, invasive breast cancer were treated with "quadrantectomy" with axillary dissection followed by electron beam radiation therapy (QUART) at the St. Bortolo Hospital, Vicenza. Stage II patients received adjuvant chemotherapy (CMF) if preperimenopausal or hormonotherapy (tamoxifen) if postmenopausal. The median follow-up was 54 months (26 to 116 months). The 4.5 year overall survival (OS) and disease-free survival (DFS) were respectively 91% and 85%; the 10-year actuarially estimated OS and DFS was 77%. Thirty-three patients relapsed, 11 of whom had local recurrence, and 23 developed distant metastases. A significantly longer OS and DFS were observed in stage I versus stage II (p = 0.0008) and in pT1 versus pT2 (p = 0.001) tumors. No difference was found regarding menopausal status and histotype. The local control of disease was very high (95.5%), with a significantly higher local recurrence rate in premenopausal women compared to postmenopausal (10/117 versus 1/126; p = 0.009). Tumor size did not influence the frequency of local recurrence. No major complications occurred but a significantly higher rate of reversible radiation pneumonitis occurred in patients treated with higher energies of electrons (17 to 20 MeV) compared with lower (6 to 13 MeV) (33/177 versus 7/66; p less than 0.05). Cosmetic results were judged as excellent in 20%, satisfactory in 68%, unsatisfactory in 6% and not evaluable in 6% of cases. We conclude first, that small pT2 breast carcinomas may also be safely treated with QUART, second, that the electron beam is a radiotherapeutic technique able to produce a good cosmetic result and to assure a satisfactory local control and, finally, that the use of tamoxifen in postmenopausal stage II breast carcinomas is safe and easy to combine with radiotherapy in the conservative management of early breast cancer due to the lower toxic effects, compared to those observed in premenopausal women treated with chemotherapy. PMID- 1746921 TI - Intraperitoneal chemotherapy with carboplatin and interferon alpha in the treatment of relapsed ovarian cancer: a pilot study. AB - In ovarian cancer patients intraperitoneal chemotherapy confers pharmacokinetic advantages and appears an attractive way to improve the efficacy of certain antineoplastic agents. Intraperitoneal carboplatin and interferon alpha have been separately evaluated in ovarian cancer "with promising results". We report a phase I-II pilot trial of intraperitoneal carboplatin 400 mg/sqm plus interferon alpha 25 x 10(6) U q 28 d in 16 patients (pts) previously treated with intravenous cisplatin based chemotherapy. All the patients had relapsed (11 pts) or refractory (5 pts) disease; residual tumors were less than 2 cm in 10 pts and greater than 2 cm in 6 pts. Local and general toxicities were moderate, with neither WHO grade 4, nor neurotoxicity and ototoxicity. Myelotoxicity was the most frequent side effect. Among 14 evaluable pts, objective responses were observed in 6 pts (42.8%) including 3 pts with pathologically confirmed complete response (21.4%); six more pts presented prolonged disease-free survival. Response occurred in both categories of pts with greater than or less than 2 cm residual disease, also in pts refractory to prior intravenous cisplatin. The proper role of intraperitoneal treatment cannot be exactly defined without large randomized trials designed to compare intraperitoneal to intravenous drug administrations. PMID- 1746922 TI - The significance of nuclear morphometric variables as prognostic predictors in breast cancer. AB - The preoperative biopsies from primary breast carcinomas of 504 women were subjected to interactive morphometric analysis of a) the mean nuclear area (NA), b) standard deviation of nuclear area (SDNA), c) mean area of the 10 largest nuclei (NAl0), d) nuclear perimeter (PE), e) standard deviation of nuclear perimeter (SPDE), f) largest nuclear diameter (Dmax) and g) shortest nuclear diameter (Dmin), h) histological grade and i) classical prognostic variables. The above data were correlated with the disease outcome during the mean follow-up period of 11.2 years. Tumor size (p less than 0.0001), morphometric variables (p = 0.0001-0.005) and histological grade (p = 0.03) predicted axillary lymph node metastasis at the time of diagnosis. According to multivariate analysis, tumour size and NA predicted the axillary lymph node metastasis independently. Axillary lymph node status (p less than 0.0001) and histological grade (p = 0.01) predicted the tumour recurrence and recurrence-free survival, whereas the morphometric variables had no significant predictive value. Axillary lymph node status (p less than 0.0001), tumour size (p less than 0.0001), histological grade (p = 0.0012) and morphometric variables (p = 0.003-0.035) predicted the disease related survival. Of the morphometric variables, NA and the Dmin were the two most important predictors of tumour-related survival in univariate analysis. Dmax had independent prognostic information in multivariate survival analysis. In the same analysis, tumour size and axillary lymph node status were more important predictors. In conclusion, the morphometric variables analysed have independent predictive value in female breast cancer. Their value is, however, inferior to that of the tumour size and axillary lymph node status, but equal to that of the histological grade. PMID- 1746923 TI - [Interferon and interleukin 2 in metastatic cancer of the kidney. Apropos of 18 cases]. AB - Eighteen patients with advanced renal cancer received a combination of IFN alpha 10 x 10(6) U/m2/Day (D) x 5D followed by Interleukin 2 (IL2) 18 x 10(6) UI/m2/D x 5 D. The median follow-up is 10 months. Four partial responses were observed lasting 7 to 13 months (22.2%). The clinical safety was satisfactory. The survival for responding patients is 12 months (median). The safety of treatment is an argument in favour of future trials in an attempt to demonstrate the benefit of combinations of biomodulators. PMID- 1746924 TI - Uretero-ileocecocapsuloplasty. Preliminary reports. AB - A uretero-ileocecocapsulaplasty and ileal patch operation was performed on seven patients following cystectomy. All the patients were carefully selected cases of unifocal T2, T3 vesical carcinoma localized at least 2-3 cm from the bladder neck. Vesical mapping and intraoperative histological examination of resection edges were negative. The operative technique is described together with early clinical and urodynamic findings. PMID- 1746925 TI - [Reversal of urinary diversion after radical surgery for rhabdomyosarcoma of the bladder]. AB - The authors report a case of reversal of urinary diversion in a 14 year old boy who had presented, three years previously with an embryonal rhabdomyosarcoma of the base of the bladder. The initial treatment had consisted of preoperative and postoperative chemotherapy combined with radical cystoprostatectomy with urinary diversion via a colonic conduit. The principle of the technique of reversal of urinary diversion are discussed in the light of this unusual case. PMID- 1746926 TI - [Cancer of the prostate: curative radiotherapy preceded by lymphadenectomy in 20 patients. Follow-up over 10 years]. AB - Twenty patients with prostatic cancer were treated by external beam radiotherapy after ilioobturator lymphadenectomy. The patients could be divided into two groups: Group I: no lymph node invasion and Group II: presence of lymph node metastases. In Group I, only one death was due to cancer and the 6-year survival was 90%. In Group II, 7 deaths were due to cancer and the 6-year survival was 20%. Secondary endocrine treated administered at the time of recurrence appeared to significantly prolong survival in comparison with the stage D1 cancers treated immediately by endocrine therapy. PMID- 1746927 TI - [Treatment trials of prostatic adenoma using local hyperthermia induced by microwaves]. PMID- 1746928 TI - [Unusual tumors of the testis. Apropos of 22 cases]. AB - The authors report their experience of rare non-germ-cell tumours of the testis over a period of 10 years. The criteria of benign disease, justifying testicular preservation in 5 out of 7 cases of epidermoid cysts, are defined. Four cases of Leydig cell tumours, including 3 with gynaecomastia, are described. Three cases of adenomatoid tumours with conservative surgery, 3 lymphomas, 2 mature teratomas and 2 cysts of the rete testis are also reported. The place of ultrasonography is defined and the possibility of conservative surgery is discussed in relation to a review of the recent literature. PMID- 1746929 TI - [Is sucrose a risk factor in calculus formation?]. AB - The addition of sucrose to drinking water of rats at the rate of 2.5 or 5 grams per 100 ml, for one month, induced hypercalciuria which appeared to be dependent on the degree of supplementation. In spite of these disorders, calcium deposits were not observed in treated animals. This protection against renal calculi was probably due to high urinary excretions of magnesium, phosphorus, zinc and copper. These lithogenesis inhibitors varied, like oxaluria and calciuria, in parallel with dietary sucrose intake. PMID- 1746930 TI - A museum showcase. Developing a special OR nurse week project. PMID- 1746931 TI - Discharge instructions. Advice for knee, shoulder arthroscopy outpatients. PMID- 1746932 TI - Procuring a laser system. PMID- 1746933 TI - The nurse as an expert witness. PMID- 1746934 TI - Cardiopulmonary resuscitation drug therapy. PMID- 1746935 TI - Mandatory HIV testing cures no one. PMID- 1746936 TI - Goals, benefits, costs, member involvement with Project Teams. PMID- 1746937 TI - Situational leadership. A tool for OR staff development. PMID- 1746938 TI - Pediatric endoscopic sinus surgery. A new approach to chronic sinus disease. PMID- 1746939 TI - Tributyltin-resistant bacteria from estuarine and freshwater sediments. AB - Resistance to tributyltin (TBT) was examined in populations from TBT-polluted sediments and nonpolluted sediments from an estuary and from fresh water as well as in pure cultures isolated from those sediments. The 50% effective concentrations (EC50s) for populations were higher at a TBT-polluted freshwater site than at a site without TBT, suggesting that TBT selected for a TBT-resistant population. In contrast, EC50s were significantly lower for populations from a TBT-contaminated estuarine site than for those from a site without TBT, suggesting that other factors in addition to TBT determine whether populations become resistant. EC50s for populations from TBT-contaminated freshwater sediments were nearly 30 times higher than those for populations from TBT contaminated estuarine sediments. We defined a TBT-resistant bacterium as one which grows on trypticase soy agar containing 8.4 microM TBT, a concentration which prevented the growth of 90% of the culturable bacteria from these sediments. The toxicity of TBT in laboratory media was influenced markedly by the composition of the medium and whether it was liquid or solid. Ten TBT-resistant isolates from estuarine sediments and 19 from freshwater sediments were identified to the genus level. Two isolates, each a Bacillus sp., may be the first gram-positive bacteria isolated from fresh water in the presence of a high concentration of TBT. There was a high incidence of resistance to heavy metals: metal resistance indices were 0.76 for estuarine isolates and 0.68 for freshwater isolates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746940 TI - Effects of time and watershed characteristics on the concentration of Cryptosporidium oocysts in river water. AB - Water samples were collected from four locations on two rivers in Washington State and analyzed by membrane filtration-immunofluorescence assay to establish Cryptosporidium oocyst concentrations. Sampling locations were selected to evaluate effects of watershed character, from pristine mountain to downstream agricultural, on oocyst concentrations. Samples were collected at six biweekly intervals from late June to early September, with two additional sets of five samples taken on separate days (one set taken at bihourly intervals and one set taken simultaneously). Cryptosporidium oocysts were found in 34 of 35 samples at concentrations ranging from about 0.2 to 65 oocysts per liter. Oocyst concentrations were highest early in the sampling period, when they were influenced by postrainfall runoff, and decreased through the summer months. Oocyst concentrations found in ten samples collected on two days (5 samples per day) showed no short-term variations. Oocyst concentrations and oocyst production per square mile (ca. 2.6 km2) of watershed found in water draining a controlled public water supply watershed were the lowest observed. The concentrations and production rates for drainage from an adjacent, comparable, but uncontrolled watershed were nearly 10 times higher. The concentration and production rates of the downstream area influenced by dairy farming were nearly 10 times higher than rates at the upstream stations. The data showed clearly that oocyst concentrations were consistently observed above the detection limit of the analytical method, about 0.1 oocysts per liter; that oocyst concentrations were continuous as opposed to intermittent; and that watershed character and management affected surface water oocyst concentrations significantly. PMID- 1746941 TI - Metabolic engineering of Klebsiella oxytoca M5A1 for ethanol production from xylose and glucose. AB - The efficient diversion of pyruvate from normal fermentative pathways to ethanol production in Klebsiella oxytoca M5A1 requires the expression of Zymomonas mobilis genes encoding both pyruvate decarboxylase and alcohol dehydrogenase. Final ethanol concentrations obtained with the best recombinant, strain M5A1 (pLOI555), were in excess of 40 g/liter with an efficiency of 0.48 g of ethanol (xylose) and 0.50 g of ethanol (glucose) per g of sugar, as compared with a theoretical maximum of 0.51 g of ethanol per g of sugar. The maximal volumetric productivity per hour for both sugars was 2.0 g/liter. This volumetric productivity with xylose is almost twice that previously obtained with ethanologenic Escherichia coli. Succinate was also produced as a minor product during fermentation. PMID- 1746942 TI - Identification of putative insect brush border membrane-binding molecules specific to Bacillus thuringiensis delta-endotoxin by protein blot analysis. AB - Binding sites for insecticidal toxins of Bacillus thuringiensis are located in the brush border membranes of insect midguts. Two approaches were used to investigate the interactions of B. thuringiensis subsp. kurstaki HD-73 CryIA(c) toxin with brush border membrane vesicles from sensitive and naturally resistant insects: 125I-toxin-vesicle binding assays and protein blots probed with 125I CryIA(c) toxin. In bioassays, Manduca sexta and Heliothis virescens larvae were highly sensitive, Helicoverpa zea larvae were moderately sensitive, and Spodoptera frugiperda larvae were resistant to CryIA(c) toxin. Studies of binding of 125I-CryIA(c) toxin to brush border membrane vesicles from the larval midguts revealed that all insects tested had high-affinity, saturable binding sites. Significantly, S. frugiperda larvae bind but are not killed by CryIA(c) toxin. Labeled CryIA(c) toxin incubated with protein blots identifies a major binding molecule of 120 kDa for M. sexta and 148 kDa for S. frugiperda. H. virescens and H. zea are more complex, containing 155-, 120-, 103-, 90-, and 63-kDa proteins as putative toxin-binding molecules. H. virescens also contains a minor toxin binding protein of 81 kDa. These experiments provide information that can be applied toward a more detailed characterization of B. thuringiensis toxin-binding proteins. PMID- 1746943 TI - Intermediates and products of synthetic lignin (dehydrogenative polymerizate) degradation by Phlebia tremellosa. AB - Agitated, nitrogen-limited cultures of Phlebia tremellosa caused substantial changes in the distribution of 14C-labelled synthetic lignin (dehydrogenative polymerizate [DHP]) between water-soluble, dioxane-soluble, alkali-soluble, and insoluble fractions before much lignin carbon was metabolized to CO2. First, the insoluble form increased at the expense of the dioxane-soluble form. Later, the amounts of alkali-soluble and water-soluble 14C increased, and release of 14CO2 began. The molecular weight distribution of the dioxane-soluble lignin remained constant during degradation, but that of the water-soluble fraction changed to higher molecular weights. Culture agitation accelerated the attachment of suspended DHP to the mycelia and stimulated production of water-soluble 14C and 14CO2. The nonionic detergent Tween 80 also hastened release of 14CO2 and increased the early conversion of dioxane-soluble DHP to the alkali-soluble and insoluble forms. Oxidative polymerization is suggested as the first step in degradation of DHP by P. tremellosa. PMID- 1746944 TI - Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25 dihydroxyvitamin D3 by using Streptomyces sp. strains. AB - To enzymatically synthesize vitamin D derivatives, we screened about 300 Streptomyces sp. strains. Streptomyces sclerotialus FERM BP-1370 and Streptomyces roseoporus FERM BP-1574 were found to have the ability to convert 25 hydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3, respectively, to 1 alpha, 25 dihydroxyvitamin D3. The average rates of 1 alpha hydroxylation of 25 hydroxyvitamin D3 were 6.9 micrograms liter-1 min-1 with FERM BP-1370 and 7.0 micrograms liter-1 min-1 with FERM BP-1574. The specific cytochrome P-450 inhibitors carbon monoxide, SKF-525-A, and metyrapone inhibited the hydroxylation of 1 alpha- and 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by FERM BP-1370 and FERM BP-1574. The cytochromes P-450 of these strains were detected by reduced CO difference spectra in the whole-cell suspensions. The appearance of cytochrome P-450 suggests that the cytochromes P-450 of FERM BP-1370 and FERM BP 1574 carry out the hydroxylation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3. PMID- 1746945 TI - Biodegradation of dichloromethane and its utilization as a growth substrate under methanogenic conditions. AB - Biodegradation of dichloromethane (DCM) to environmentally acceptable products was demonstrated under methanogenic conditions (35 degrees C). When DCM was supplied to enrichment cultures as the sole organic compound at a low enough concentration to avoid inhibition of methanogenesis, the molar ratio of CH4 formed to DCM consumed (0.473) was very close to the amount predicted by stoichiometric conservation of electrons. DCM degradation was also demonstrated when methanogenesis was partially inhibited (with 0.5 to 1.5 mM 2 bromoethanesulfonate or approximately 2 mM DCM) or completely stopped (with 50 to 55.5 mM 2-bromoethanesulfonate). Addition of a eubacterial inhibitor (vancomycin, 100 mg/liter) greatly reduced the rate of DCM degradation. 14CO2 was the principal product of [14C]DCM degradation, followed by 14CH4 (when methanogenesis was uninhibited) or 14CH3COOH (when methanogenesis was partially or completely inhibited). Hydrogen accumulated during DCM degradation and then returned to background levels when DCM was consumed. These results suggested that nonmethanogenic organisms mediated DCM degradation, oxidizing a portion to CO2 and fermenting the remainder to acetate; acetate formation suggested involvement of an acetogen. Methanogens in the enrichment culture then converted the products of DCM degradation to CH4. Aceticlastic methanogens were more easily inhibited by 2-bromoethanesulfonate and DCM than were CO2-reducing methanogens. When DCM was the sole organic-carbon and electron donor source supplied, its use as a growth substrate was demonstrated. The highest observed yield was 0.085 g of suspended organic carbon formed per g of DCM carbon consumed. Approximately 85% of the biomass formed was attributable to the growth of nonmethanogens, and 15% was attributable to methanogens. PMID- 1746946 TI - Degradation of organochlorine compounds in spent sulfite bleach plant effluents by actinomycetes. AB - Actinomycetes isolated from different soil samples were tested for their abilities to utilize spent sulfite bleach effluents from a paper mill. Degradation and dechlorination of the chlorinated compounds in the effluents of the first two bleaching stages, i.e., chlorination stage [(C + D)red.] and alkaline extraction stage (E1O), were monitored by determining total organic carbon (TOC) and activated-carbon-adsorbable organic-bound halogen (AOX). The isolates showed increased degradation rates after repeated incubations in the effluent-containing medium. Separation of the culture supernatants by ultrafiltration into three fractions of different molecular weights revealed substantial AOX and TOC reductions in the low-molecular-weight fraction. The AOX values of the higher-molecular-weight fractions were also reduced. Extracellular peroxidase and cell wall-bound catalase activities were produced during growth of the microorganisms on bleach effluents. PMID- 1746947 TI - Effect of 2-hydroxybenzoate on the maintenance of naphthalene-degrading pseudomonads in seeded and unseeded soil. AB - The addition of specific nontoxic inducers of catabolic operons to contaminated sites is an approach that may enhance the efficiency of in situ biodegradation. We determined the genetic response of six pseudomonads to salicylate (also known as 2-hydroxybenzoate) added directly to 50 g of nonsterile soil samples. The strains, isolated from a polyaromatic hydrocarbon-contaminated soil, metabolized naphthalene as the sole source of available carbon, and their DNA sequences show significant homology to the nahAB genes of the degradative plasmid NAH7. Duplicate nonsterile soil cultures were incubated for up to 30 days. Experimental soil cultures were seeded with naphthalene-degrading strains (10(8) CFU g-1) originally isolated from the soil and amended with salicylate (16 or 160 micrograms g-1). Soil samples were analyzed periodically for the population density of heterotrophic bacteria and naphthalene degraders and for the abundance of the naphthalene-degradative genotype in the bacterial community. At 160 micrograms g-1, salicylate sustained the density of naphthalene degraders at the introduced density for 30 days in addition to producing a two- to sixfold increase in the occurrence in the bacterial community of DNA sequences homologous to the nah operon. No change in recoverable bacterial population densities was observed when soil samples were amended with 16 micrograms of salicylate g-1, but this concentration of salicylate induced a significant increase in the level of nah-related genes in the population. PMID- 1746948 TI - Subcloning of bph genes from Pseudomonas testosteroni B-356 in Pseudomonas putida and Escherichia coli: evidence for dehalogenation during initial attack on chlorobiphenyls. AB - The bphA, -B, -C, and -D genes from Pseudomonas testosteroni B-356 were mapped to a 5.5-kb DNA fragment of cloned plasmids pDA1 and pDA2 by use of deletion and insertion mutants of these plasmids. The expression of each of these genes was evaluated in Escherichia coli and in Pseudomonas putida, and it was found that the bphC and bphD genes are well expressed in both E. coli and P. putida cells while the bphA and bphB genes are very poorly expressed in E. coli, even when placed downstream of a tac promotor. P. putida clones carrying the bphA gene were used to study the metabolites produced from 4,4'-dichlorobiphenyl, 2,2' dichlorobiphenyl, and 2,4'-dichlorobiphenyl. It was shown that dehalogenation of 4-Cl and 2-Cl occurs in the course of the initial oxygenase attack on these molecules, which always occurs on carbons 2 and 3, independently of the positions of the chlorine atoms. Our data also suggest that in the case of polychlorobiphenyl congeners carrying chlorine atoms on both rings, it appears that, depending on the chlorine positions, dioxygenation will occur predominantly on one ring over the other. However, attack of the more resistant ring is not excluded, resulting in multiple conversion pathways. PMID- 1746949 TI - Site-specific mutagenesis method which completely excludes wild-type DNA from the transformants. AB - A highly efficient site-specific mutagenesis method has been devised to exclude wild-type DNA from incorporation into the transformed cells. Two complementary oligonucleotides, corresponding to a target sequence of a DNA molecule and containing an insertion mutation which created an endonuclease restriction site, were synthesized. By using the wild-type DNA molecule flanked by two restriction sites on each side of the target region as a template, the two oligonucleotide primers were extended, enriched, and isolated. The extended products, in turn, were used as templates in a polymerase chain reaction to obtain a mutagenized double-stranded DNA fragment which was conveniently cloned into plasmids by using the flanking restriction sites. Escherichia coli cells transformed by these plasmids were subject to large-scale analysis. One hundred percent of the transformants examined by colony hybridization, restriction enzyme analysis, and DNA sequencing were found to contain the mutant DNA sequence. PMID- 1746950 TI - 7-Mercaptoheptanoylthreonine phosphate substitutes for heat-stable factor (mobile factor) for growth of Methanomicrobium mobile. AB - Methanomicrobium mobile requires a heat-stable factor present in ruminal fluid and in boiled cell extract from Methanobacterium thermoautotrophicum for growth. By comparing the growth of M. mobile with boiled cell extract with that observed with various methanogenic cofactors, we found that 7-mercaptoheptanoylthreonine phosphate (HS-HTP) supported sustained growth of M. mobile, at an optimal concentration of 100 microM. No derivatives or possible biosynthetic precursors of HS-HTP could replace HS-HTP as the sole source of growth factor. Results suggest that the growth requirement might be satisfied by 7-mercaptoheptanoic acid plus a second, unidentified heat-stable factor. PMID- 1746951 TI - Expression of the Escherichia coli beta-glucuronidase gene in Pseudocercosporella herpotrichoides. AB - The plant-pathogenic fungus Pseudocercosporella herpotrichoides has been successfully transformed by using two different positive selection systems in combination with the Escherichia coli gusA gene. The selectable markers used in this study were the hygromycin B phosphotransferase gene (hph) from E. coli and the gene (bml) for beta-tubulin from a benomyl-resistant mutant of Neurospora crassa. A lower transformation rate was obtained with the bml system than with the hph system. Conversely, cotransformation frequencies, as determined with medium plates containing the chromogenic substrate 5-bromo-4-chloro-3-indolyl beta-D-glucuronic acid, were higher with bml than with hph as the selectable marker. The hygromycin-resistant transformants were mitotically stable, and both the selectable gene and gusA were maintained through conidiation. The vector DNA was integrated into the genome, and the number and sites of insertion varied among transformants. Enzyme assays of mycelial extracts showed that beta glucuronidase activity was highest in transformants with a high gusA copy number. Expression of gusA during growth of the fungus on plants was easily detectable and did not affect pathogenicity. These results form the basis for construction of a versatile and sensitive reporter gene system for P. herpotrichoides. PMID- 1746952 TI - Aflatoxin production via cross-feeding of pathway intermediates during cofermentation of aflatoxin pathway-blocked Aspergillus parasiticus mutants. AB - Cofermentation of Aspergillus parasiticus strains (SRRC 163 and SRRC 2043) blocked at different steps in the aflatoxin B1 (AFB1) biosynthetic pathway in a synthetic liquid medium or on seeds (cottonseed, corn kernels, and peanuts) resulted in production of AFB1. Strain SRRC 2043 accumulated O methylsterigmatocystin (OMST), a late precursor in AFB1 biosynthesis, whereas SRRC 163 accumulated averantin, an early precursor in the pathway. Strain SRRC 2043 secreted large amounts of OMST in culture relative to the amounts of several other pathway intermediates secreted into media (by other AFB1 pathway-blocked strains). AFB1 production occurred even when colonies of SRRC 163 and SRRC 2043 strains (producing no detectable AFB1) were grown together on an agar medium while physically separated from each other by a filter membrane (0.22-micron pore size). In addition, when mycelia of strain SRRC 163 were added to culture filtrates (containing no mycelia but containing secreted OMST) of strain SRRC 2043, AFB1 production occurred. The results suggested a chemical (rather than genetic) mechanism of complementation for AFB1 production between AFB1 pathway blocked strains, since no mycelial contact was required between these strains for AFB1 production. The mechanism for chemical complementation involves secretion of OMST by SRRC 2043 and subsequent absorption and conversion of OMST to AFB1 by mycelia of strain SRRC 163. PMID- 1746953 TI - Possible mechanisms underlying the slow lactose fermentation phenotype in Shigella spp. AB - A Southern hybridization analysis revealed that the region homologous to Escherichia coli lacZ was present on the chromosomal DNAs of beta-galactosidase positive Shigella strains, such as Shigella dysenteriae serovar 1 and Shigella sonnei strains, whereas this region was absent from chromosomal DNAs of beta galactosidase-negative strains of Shigella flexneri and Shigella boydii. We found that the lacY-A region was deficient in S. dysenteriae serovar 1 and believe that this is the reason for the slow fermentation of lactose by this strain. S. sonnei strains possessed the region which hybridized with E. coli lacY-A despite their slow hydrolysis of lactose. The whole lactose-fermenting region was cloned from S. sonnei and compared with the cloned lac operon of E. coli K-12. Both clones directed the synthesis of beta-galactosidase in an E. coli K-12 strain lacking indigenous beta-galactosidase activity (strain JM109-1), and we observed no difference in the expression of beta-galactosidase activity in S. sonnei and E. coli. However, E. coli JM109-1 harboring the lactose-fermenting genes of S. sonnei exhibited the slow lactose fermentation phenotype like the parental strain. S. sonnei strains had no detectable lactose permease activities. E. coli JM109-1 harboring the lactose-fermenting genes of S. sonnei had a detectable permease activity, possibly because of the multicopy nature of the cloned genes, but this permease activity was much lower than that of strain JM109-1 harboring the lac operon of E. coli K-12. From these results we concluded that slow lactose fermentation by S. sonnei is due to weak lactose permease activity. PMID- 1746954 TI - Distribution of Legionella spp. in hydrothermal areas in continental Portugal and the island of Sao Miguel, Azores. AB - Nineteen aquatic environment sites from three hydrothermal areas on continental Portugal and one area on the island of Sao Miguel, Azores, were examined for the recovery of Legionella spp. Physicochemical and bacteriological parameters were also determined for each site. Water temperatures varied between 22 and 67.5 degrees C, although the majority had temperatures above 40 degrees C; the pH varied between 5.5 and 9.2. The number of Legionella spp. recovered varied between 5.0 x 10(2) and 2.3 x 10(6) CFU/liter. A total of 288 isolates from 14 sites were identified by indirect immunofluorescence assay. The majority of the isolates belonged to Legionella pneumophila (74.3%), of which most belong to serogroup 1, but the relative proportion of L. pneumophila serogroups varied considerably. L. pneumophila serogroup 1 constituted 96.2% of the isolates in area 2 from central Portugal, but no isolates of this serogroup were recovered from Sao Miguel, where serogroup 6 strains were the predominant isolates. Ninety six percent of the L. pneumophila serogroup 1 isolates belonged to monoclonal antibody subgroups OLDA and Bellingham. Other species identified were L. bozemanii serogroup 2, L. dumoffii, L. micdadei, L. moravica, L. oakridgensis, L. sainticrucis, and L. sainthelensi. Two undescribed species, which react by indirect immunofluorescence assay to antisera to "L. londoniensis" and "L. nautarum" and a group of isolates with strong cross-reaction to L. cincinnatiensis/L. sainticrucis/L. longbeachae by indirect immunofluorescence assay were also recovered. The latter were the only isolates recovered from area 3, in east central Portugal, over a period of 1 year. PMID- 1746955 TI - Detection and production of verotoxin 1 of Escherichia coli O157:H7 in food. AB - Verotoxin 1 (VT1) is a recognized virulence factor of Escherichia coli O157:H7, a cause of severe food-borne disease. The public health significance of preformed verotoxin in food is unknown, and relatively little research has been done to determine the production of VT1 in food. The purposes of this study were to develop a sensitive method to detect VT1 in milk and in ground beef and to determine the conditions for VT1 production in these foods. A sandwich enzyme linked immunosorbent assay in which we used VT1-specific monoclonal antibody 9C9F5 as the capture antibody and a rabbit polyclonal antibody raised against VT2 as the detection antibody was developed for the detection and quantification of VT1 in milk and in ground beef. The enzyme-linked immunosorbent assay was sensitive to a minimum of 0.5 ng of VT1 per ml of milk and 1.0 ng of VT1 per g of ground beef. The greatest amount of VT1 detected in milk (306 ng/ml) was detected in samples that were incubated at 37 degrees C with agitation (160 rpm) for 48 h. Very little toxin (1 ng/ml) was produced at 25 or 30 degrees C within 96 h. VT1 production was greater in ground beef than in milk; 452 ng of VT1 per g was produced in beef at 37 degrees C in 48 h. Relatively little VT1 was produced in beef within 96 h at 25 and 30 degrees C (2.1 and 9.8 ng of VT1 per g, respectively). Our results indicate that ground beef is a better medium for VT1 production than milk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746956 TI - Inhibition of pure cultures of methanogens by benzene ring compounds. AB - The inhibition of methane production by Methanosaeta concilii GP6, Methanospirillum hungatei GP1, Methanobacterium espanolae GP9, and Methanobacterium bryantii M.o.H. during short-term (6-h) exposure to eight benzene ring compounds was studied. The concentration that caused 50% inhibition of the methane production rate (IC50) was dependent on the species and the toxicant. Pentachlorophenol was the most toxic of the tested compounds, with an IC50 of less than 8 mg/liter for all species except M. hungatei. Abietic acid was the next most toxic compound for all the species, with an IC50 in the range of 21.4 to 203 mg/liter. Sodium benzoate was generally the least toxic, with an IC50 in the range of 1,225 to 32,400 mg/liter. 3-Chlorobenzoate was substantially more toxic (IC50, 450 to 1,460 mg/liter) than benzoate. The inhibition by benzene, phenol, vanillic acid, and toluene was intermediate to that of pentachlorophenol and benzoate. Long-term incubation (days) studies to determine effect on growth indicated that all eight compounds were usually much more toxic than predicted from the short-term data. In these latter studies, there was generally a good correlation in the observed inhibition as determined from growth and methane production. PMID- 1746957 TI - Taxonomic relationships among strains of the anaerobic bacterium Bacteroides ruminicola determined by DNA and extracellular polysaccharide analysis. AB - DNA and extracellular polysaccharide (EPS) analyses were performed on 14 strains of Bacteroides ruminicola. The guanine-plus-cytosine (G+C) base contents, determined from the buoyant densities of chromosomal DNAs, showed a broad range of values, from 37.6 to 50.9 mol%. DNA hybridization showed generally low DNA relatedness among the strains. Seven strains formed two groups of closely related bacteria consisting of five (group 1) and two (group 2) strains, and another strain, E42g, showed moderate relatedness to group 1 strains. However, the remaining six strains were not related to any of the other strains. DNA reassociation indicates that the strains constitute a genetically diverse group representing as many as nine separate species. EPS analysis showed that the strains produced EPS with rather uniform sugar compositions, which did not correlate with strain relationships determined by DNA analysis. Four strains had EPS with acidic sugars or unknown compounds. The EPS of strain 20-63 contained the unusual acidic sugar 4-O-(1-carboxyethyl)-rhamnose. This monosaccharide has been shown to occur in nature in only one other bacterial species. PMID- 1746958 TI - Substrate interactions of benzene, toluene, and para-xylene during microbial degradation by pure cultures and mixed culture aquifer slurries. AB - Benzene, toluene, and p-xylene (BTX) were degraded by indigenous mixed cultures in sandy aquifer material and by two pure cultures isolated from the same site. Although BTX compounds have a similar chemical structure, the fate of individual BTX compounds differed when the compounds were fed to each pure culture and mixed culture aquifer slurries. The identification of substrate interactions aided the understanding of this behavior. Beneficial substrate interactions included enhanced degradation of benzene and p-xylene by the presence of toluene in Pseudomonas sp. strain CFS-215 incubations, as well as benzene-dependent degradation of toluene and p-xylene by Arthrobacter sp. strain HCB. Detrimental substrate interactions included retardation in benzene and toluene degradation by the presence of p-xylene in both aquifer slurries and Pseudomonas incubations. The catabolic diversity of microbes in the environment precludes generalizations about the capacity of individual BTX compounds to enhance or inhibit the degradation of other BTX compounds. PMID- 1746959 TI - Deletion of pgi alters tryptophan biosynthesis in a genetically engineered strain of Escherichia coli. AB - Deletion of the structural gene for phosphoglucose isomerase (pgi) of Escherichia coli dramatically alters the path of glucose catabolism by diverting carbon into the hexose monophosphate shunt. The effect of this genetic alteration on the conversion of glucose to tryptophan by strains optimized for the biosynthesis of this amino acid was determined by using 13C-nuclear magnetic resonance spectroscopy in vivo. Pgi- strains converted glucose to tryptophan almost twice as efficiently as did their Pgi+ counterparts. PMID- 1746960 TI - Selection and application of Streptococcus bovis as a silage inoculant. AB - Three strains of Streptococcus bovis, a homolactic bacterium capable of utilizing starch, were evaluated for growth kinetics and ability to decrease the pH of alfalfa silage. A selected strain was evaluated for its competitiveness as an inoculant with Enterococcus faecium, an organism used in inoculants, and for its ability to enhance the effect of a commercial inoculant. Testing was completed over three studies using wilted alfalfa (28 to 34% dry matter) ensiled into laboratory silos. Treatments were control, E. faecium, E. faecium and commercial inoculant, S. bovis, and S. bovis and commercial inoculant. Replicate silos were emptied and analyzed at 0.5, 1, 2, 4, 8, and 40 days for pH, fermentation products, and nitrogen fractions. S. bovis alone lowered the pH quicker and improved silage parameters early in the fermentation compared with E. faecium, the commercial inoculant, and control treatments. When combined with a commercial inoculant, S. bovis lowered pH more quickly than the commercial inoculant alone and E. faecium plus commercial inoculant. At 40 days, S. bovis combination had lower pH and ammonia nitrogen and acetate contents than the E. faecium combination. Starch in the silage was not utilized by S. bovis as had been anticipated. Results indicate that S. bovis was more effective than E. faecium as a silage inoculant and could enhance a commercial inoculant on low-dry-matter alfalfa. PMID- 1746961 TI - Phenotypic characterization of CO2-requiring strains of Streptococcus bovis from koalas. AB - We examined phenotypic characteristics of six mannitol-fermenting strains of Streptococcus bovis, including two unusual CO2-requiring strains isolated from koala feces. These strains did not grow in air, but grew in air supplemented with CO2 and under reduced oxygen conditions. All six strains had the same biochemical characteristics, except that the CO2-requiring strains did not produce beta-N acetylglucosaminidase. PMID- 1746962 TI - Enumeration of Flexibacter canadensis in environmental samples by using a bacteriophage isolated from soil. AB - The denitrifier Flexibacter canadensis, in the presence of sulfide, can reduce N2O in the presence of concentrations of C2H2 which normally inhibit N2O reduction. Most-probable-number estimates of naturally occurring F. canadensis populations in various soils and sediments were made with a bacteriophage which is active against and specific for a strain of denitrifying F. canadensis (Is 11). Our survey suggests that F. canadensis is common in the natural environment. PMID- 1746963 TI - Development of an improved chemically defined minimal medium for Listeria monocytogenes. AB - A chemically defined minimal medium for Listeria monocytogenes has been developed by modification of Welshimer's medium. The growth factors required by L. monocytogenes Scott A are leucine, isoleucine, arginine, methionine, valine, cysteine (each at 100 mg/liter), riboflavin and biotin (each at 0.5 micrograms/ml), thiamine (1.0 micrograms/ml), and thioctic acid (0.005 micrograms/ml). Growth was stimulated by 20 micrograms of Fe3+ per ml as ferric citrate. Glucose (1%) and glutamine (600 mg/liter) are required as primary sources of carbon and nitrogen. Glucose could not be replaced by various organic acids or amino acids. Of several sugars tested, fructose, mannose, cellobiose, trehalose, maltose (weak), glycerol (weak), and the amino sugars glucosamine, N acetylglucosamine, and N-acetylmuramic acid supported growth in the absence of glucose. Evidence was found that chitin and cell walls of starter bacteria (Lactococcus lactis) supported survival of L. monocytogenes, which suggests that the pathogen may obtain carbon and energy sources during colonization of some foods, such as cheeses, by assimilating bacteria or molds that are present. PMID- 1746964 TI - Kinetics of Saccharomyces cerevisiae elimination from the intestines of human volunteers and effect of this yeast on resistance to microbial colonization in gnotobiotic mice. AB - When healthy volunteers were given a daily dose of 3 x 10(8) life-dehydrated Saccharomyces cerevisiae cells for 5 days, the volunteers excreted 10(5) living yeast cells per g of feces at first, but the yeast cells disappeared within 5 days of the end of treatment. In gnotobiotic mice, S. cerevisiae administered alone colonized the intestinal tract but did not interfere with previous or subsequent colonization by a variety of potentially enteropathogenic microorganisms. When these microorganisms were present, the intestinal counts of S. cerevisiae were greatly reduced. PMID- 1746965 TI - [Outpatient cancer chemotherapy employing implantable systems]. AB - Outpatient cancer chemotherapy (OCC) employing implantable systems was introduced and the objects, conditions and problems of OCC were discussed based on experiences in 324 cases. The aims of OCC are improved QOL and the continuation of chemotherapy. Our requirements are safety, effectiveness, easy management and non-disturbance of activity. Implantable systems are very useful for OCC, especially continuous infusion combined with ambulatory pumps. However, the improvement of ambulatory pumps and the establishment of methods to evaluate OCC are required to further develop OCC. PMID- 1746966 TI - [Evaluation of induced hypertension chemotherapy (IHC) in ambulatory cancer patients]. AB - To evaluate ambulatory cancer chemotherapy (ACC), the clinical response, dose intensity of anticancer drugs, toxicities, ambulatory periods (AP) and survival days (SD) were analysed among 20 outpatients with various types of advanced cancer who were continuously treated by angiotensin II-IHC for the past 10 years. ACC was assessed with a questionnaire by the patients themselves or their families. In advanced cancer, at first, it was essentially to obtain a get clinical response or to stabilize the condition for a while, and secondly, to upgrade the performance status in better grade. Although AP and SD were so differed with the individuals: AP/SD = 1692.2 +/- 1450.2 days/2075.0 +/- 1348.0 days for CR (n = 5); 1086.0 +/- 1160.2 days/1344.3 +/- 1143.7 days for PR (n = 10); and 197.3 +/- 129.2 days/471.7 +/- 362.5 days for PD (n = 3). Alopecia, nausea/vomiting and appetite loss were the most frequent side effects, though these were almost completely controllable by ACC. Patients and their families could be cooperated and allow receiving ACC. The key in fighting cancer is the formation of good human relationship between medical oncologists and patients (including their families) mutual confidence, and giving a sufficient explanation for therapies. PMID- 1746967 TI - [Maintenance of housewife activity and the quality of familiar interactions by home continuous infusion chemotherapy in patients with recurrent gynecological cancer]. AB - Sixteen patients with recurrent gynecologic cancer were studied to evaluate maintenance of housewife activity and the quality of familiar interactions by the home continuous infusion of CDDP at a daily dose of 5 mg/body. A total dose of CDDP in one course was 100 mg/body, and more than one course was performed in every patient. Eight patients underwent intra-arterial infusion of CDDP by the 20 day continuous infusion and another 8 patients intra-venous infusion by 5-day continuous infusion every other week. The average caloric intake was 2201 kcal measured by the record of a three-day food intake during the treatment. 88% of the patients arouse between 6 and 7 in the morning, and all the patients cooked breakfast and supper, went shopping for food materials, cleaned a house and did the washing with the help of her family. All the patients accepted the treatment and were satisfied with it but appeared anxious about recurrence. Information or advice by the doctor was important to relieve their anxiety. Their husbands also accepted the treatment and tolerated well their wives, continuation of home therapy. PMID- 1746968 TI - [Total parenteral nutrition for home therapy in cancer patients]. AB - Home parenteral nutrition (HPN) was used in 14 cancer patients within a 4-yr and 4-month period. Indications included severe malabsorption, short bowel syndrome, radiation enteritis, and malignancies. The mean duration of HPN was 184 days (range: 21-706 days). HPN duration for patients with benign causes (BP) was longer [427 days (range: 176-706 days)] than for cancer-related patients (CP) [49 days (range: 21-121 days)]. The mean catheter life spans to date for BP and CP have been 596 days (range: 187-1173 days) and 127 days (range: 73-278 days), respectively. Serious catheter problems occurred 4 times in BP with the external catheter. Metabolic complications with clinical symptoms occurred in one BP who had short bowel syndrome. We followed with an evaluation of the quality of life of HPN patients. Three in 14 cases returned to work, two of them part time, and two others did most of the housekeeping, but 9 remained at home receiving only outpatient treatment. Some physical distress was recorded in all but one case. We concluded that HPN for cancer patients is a relatively safe, effective means of improving and maintaining the nutritional status, and it can reduce the length of hospitalization. We attempted to evaluate whether these patients were able to achieve a meaningful and satisfactory social and familial life. Our study was not sufficient to assess the psychological and social problems. We should establish criteria for quality of life to evaluate overall satisfaction with conditions of life under HPN. PMID- 1746969 TI - [Nutritional support for cancer bearing patients]. AB - A care system for cancer bearing patients at a highly advanced stage should be informed by a better quality of life based on a life style of the patients and their families. These patients are suffering from various types of trouble including pain, loss of appetite and nausea, which preclude oral intake. Radiotherapy or chemotherapy can be another factor aggravating their nutritional state. In terms of nutritional management, intravenous or enteral alimentation is indispensable, but these conventional alimentary supports generally lead to prolonged hospitalization and re-admission. If parenteral nutritional care can be given to patients at home and not in the hospital, it is leading to the improved quality of life would result. We focus on the issue of home alimentary care, especially intravenous alimentation, for cancer patients at the terminal stage from the nursing standpoint. PMID- 1746970 TI - [A comparative clinical study of adjuvant chemotherapy of tumors in the head and neck areas by means of HCFU]. AB - In order to evaluate the efficacy of HCFU as an adjuvant chemotherapy agent for squamous cell carcinoma of the head and neck areas, a randomized comparative study was performed with cooperative facilities. 191 patients who had undergone radical therapy were randomly assigned to the following two groups: Group A was the control group, which underwent radical therapy only, and Group B was a group which received long-term HCFU administration (300-600 mg/day x 12 weeks or more). In the comparison of non-recurrence rate in both groups, Group B had better results among patients who were at the advanced clinical stages such as N1 through N3, Stage II (p = 0.0583) and Stage III (p = 0.0970). The adverse reactions to HCFU included pollakiuria, feverishness, and digestive symptoms, but these were mild and the recovery was possible. PMID- 1746971 TI - [Pharmacokinetics of KRN 8602 in cancer patients]. AB - The pharmacokinetic properties of KRN 8602, an anthracycline compound, was studied by HPLC following intravenous administration of KRN 8602 to cancer patients. The results were as follows. (1) The plasma concentration-time curve declined as a triphasic function (alpha, beta, gamma) (t1/2 (alpha) = 0.02910, +/ 0.0054 hr, t1/2 (beta) = 0.704 +/- 0.319 hr, t1/2 (gamma) 8.37 +/- 1.37 hr). The blood cell concentration was higher than that in plasma. (2) The distribution volumes of the tissue compartment were larger than those of the central compartment. This result suggested that KRN 8602 would be easily transferred into the tissues. (3) The area under the curve (AUC) of KRN 8602 increased in proportion to the increase of dosage. (4) The metabolites of KRN 8602 were detected in plasma, blood cell and urine. (5) Urinary excretion of KRN 8602 and its metabolites were extremely low. PMID- 1746972 TI - [Inhibitory effect of UFT on rat hepatocarcinogenesis induced by 3'-methyl-4 dimethylaminoazobenzene and phenobarbital promotion]. AB - Inhibitory effect of UFT on hepatocarcinogenesis in rats induced by 3'-methyl-4 dimethylaminoazobenzene (3'-MeDAB) and phenobarbital (PB) promotion was studied. Donryu male rats were divided into four groups. Group A was fed a diet containing 0.06% 3'-MeDAB for 3, 5, or 7 weeks, and then fed normal diet for 2 weeks, subsequently received a diet containing 0.05% PB. Group B was given UFT (20 mg/kg/5 days a week) simultaneously with feeding 3'-MeDAB. Group C was given UFT simultaneously with feeding PB. Group D was given 3'-MeDAB alone. In all groups, the development of hepatocellular carcinoma was investigated 37 weeks later and the number and area per mm2 of induced glutathione S-transferase placental form (GST-P) positive foci were measured using an image processor. The number and area of GST-P positive foci in group B and group C were markedly decreased as compared with those in group A. These results seem to show that the administration of UFT inhibited the production of GST-P positive foci and that stronger inhibitory effect of UFT was observed by simultaneous administration of an initiator than by that of a promoter. PMID- 1746973 TI - [Complete response in a case of rectal carcinoma with multiple liver metastasis treated by infuse-a-port]. AB - Much effort has been developed to control of multiple liver metastases of colo rectal cancer, but the results of various therapies are not necessarily satisfactory. We report here a 73-year female with advanced rectal cancer and multiple liver metastases (H3), who showed a complete response to hepatic arterial infusion of mitomycin C using "Infuse-a-port". Hepatic arterial infusion of chemotherapeutic agents using totally implantable reservoir might be one of the most potent therapies for non-resectable liver metastasis of colo-rectal cancer. PMID- 1746974 TI - [A case of colon cancer with severe anal bleeding caused in a preoperative chemotherapy]. AB - UFT was orally administered at a dose of 600 mg/day as a preoperative chemotherapy for a 44-year old male with colon cancer. On the seventh day of the administration, severe anal bleeding occurred, and an emergent colectomy was performed. The macroscopic findings of the resected tumor were different from the first endoscopic picture, and the histopathological findings showed the significant effects of preoperative chemotherapy. PMID- 1746975 TI - [Studies on a slow releasing anticancer agent for prevention of peritoneal recurrence of advanced gastrointestinal carcinomas (experimental study)]. PMID- 1746976 TI - [Effects of urinastatin on prevention of cisplatin induced nephrotoxicity]. PMID- 1746977 TI - Transmission and epidemiology of newly transmitted falciparum malaria in the central highland plateaux of Madagascar. AB - The recent reappearance of Plasmodium falciparum in the central highland plateaux of Madagascar has led to an important increase in both morbidity and mortality in the population. To understand the phenomena that originated this outbreak, and to evaluate the clinical and biological reactions of the population, we conducted entomological surveys during the whole malaria transmission season of 1988. In parallel, 41 individuals presenting with a malaria attack in January were given a curative antimalarial treatment and were followed weekly for 20 weeks, until the end of the transmission season, in June. During the follow-up, individuals presenting with a clinical malaria attack or with a parasite density above 5000 per mm3 of blood were again given antimalarial treatment. Overall, individuals presented with an average of 5.6 thick blood smears positive for P. falciparum, and 1.4 malaria attacks requiring treatment. Plasmodium falciparum prevalence rates gradually increased to 53.8% in April, one to two months after the observed peak of transmission, then decreased to 15.4% at the end of follow-up. The proportion of P. falciparum infections with clinical symptoms did not follow a similar temporal evolution and was significantly lower than at enrollment. Splenic rates gradually decreased from 29.3-2.6%, while anti-P. falciparum and anti-Pfl55/RESA antibodies increased. For the whole transmission season individuals experienced a mean 1.5 infective bites; the malaria vectors were Anopheles gambiae s. 1 and An. funestus. This study demonstrates that, in this population newly exposed to P. falciparum infections, almost all sporozoite inoculations lead to blood parasite infection requiring treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1746978 TI - Anaplasmosis in Uganda. II. Prevalence of bovine anaplasmosis in Uganda. AB - The prevalence of bovine anaplasmosis was studied in 320 Zebu cattle randomly selected from three regions of Uganda: (Central, Southwestern and Northwestern) using dot-ELISA, Western immunoblotting, rapid card agglutination test (RCAT), capillary tube agglutination test (CAT), complement fixation test (CFT), and parasitological techniques. Dried blood on Whatman filter paper No. 1 was eluted in PBS 0.05% Tween 20 prior to testing at an initial dilution of 1:25. The prevalences of parasitaemia were 25% in the central region, 28% in the southwestern region, and 35% in the northwestern region, and the serological prevalence was lowest in the central region and highest in the northwest. Overall, prevalence rates obtained by dot-ELISA (61.9%) and Western immunoblotting (62.5%) were 1.5 times those obtained by RCAT (41%) and three times those obtained by CAT (22.5%). The overall prevalence rates obtained by dot ELISA and Western immunoblotting compared favourably with the CFT data. The present data utilizing dried blood on filter papers indicate that there is a high prevalence of anaplasmosis in those regions of Uganda surveyed, and confirm our observations and those of others that collecting blood on filter papers is a suitable technique for large scale screening and for seroepidemiological studies. PMID- 1746979 TI - Description of a mono-screen trap for Glossina fuscipes fuscipes Newstead in Uganda. AB - A low-cost mono-screen trap for Glossina fuscipes fuscipes suitable for use by a rural community in Uganda is described. The trap has a single blue/black screen and a cone made from mosquito netting. The supporting framework is made from indigenous plant materials. The differences in trap catches between the mono screen, biconical, pyramidal and vavoua traps were highly significant (P less than 0.001). Taking the standard biconical trap as control, the mono-screen trap was 1.25 times as efficient and the pyramidal trap was 0.04 times as efficient. The cost of one mono-screen trap is estimated as 1800 Uganda shillings (= U.S. $4.7), about half the cost of a pyramidal trap and one-quarter the cost of a biconical trap. The prospects for the use of the mono-screen trap by the community are discussed. PMID- 1746980 TI - A new approach to community participation in tsetse control in the Busoga sleeping sickness focus, Uganda. A preliminary report. AB - A process is described by which trapping technology is being taught to a rural community which has been affected continuously by an epidemic of sleeping sickness for over a decade. Through a systematic health education programme, people are actively involved in making and setting traps and in learning about the general characteristics of the tsetse fly and the disease. A mono-screen trap has been developed for community use and is being used to trap flies. This is the first time that this kind of community participation has been attempted in tsetse control--and this approach is discussed in relation to other approaches. PMID- 1746981 TI - Leishmania major: resistance of promastigotes to paromomycin, and susceptibility of amastigotes to paromomycin-methylbenzethonium chloride ointment. AB - Cutaneous lesions caused by Leishmania major in BALB/c mice were cured completely when treated topically with an ointment comprising 15% paromomycin sulphate and 1 2% methylbenzethonium chloride ointment in soft white paraffin twice daily for 10 days. No parasites were detected in tissue smears or in cultures from treated cutaneous lesions. Re-developing lesions, considered to be resulting from the migration of parasites from internal organs, showed almost the same response to topical treatment. Promastigotes of the virulent clone 121 of L. major LRC-L137 which were exposed to 100 micrograms ml-1 of paromomycin in RPMI medium at 28 degrees C developed resistance to the drug over 10 passages of exposure. Enzyme analysis of susceptible and resistant promastigotes of this clone showed no differences with regard to their profiles based on 11 enzymes. PMID- 1746982 TI - The development of Onchocerca dukei and O. ochengi microfilariae to infective stage larvae in Simulium damnosum s.l. and in members of the S. medusaeforme group, following intra-thoracic injection. AB - Neonate Simulium females from an endemic area of human and bovine onchocerciasis in North-Cameroon were injected in one set of experiments with microfilariae (mff) of Onchocerca dukei and in another with mff of O. ochengi. Onchocerca dukei was found to develop to infective third-stage larvae in Simulium flies: 148 third stage larvae (28.1% of injected mff) were recovered in S. hargreavesi, seven (10.4% of injected mff) in S. vorax, and 12 (1.3%) in S. damnosum s.l. Onchocerca ochengi mff developed in S. hargreavesi at a rate of 17.3% and in S. damnosum s.l. at 16.1%, yielding a total of 77 and 32 third-stage larvae respectively. Onchocerca dukei infective larvae had a mean length of 717.3 microns and a mean maximum diameter of 17.5 microns, and were slightly shorter and conspicuously thinner than those of O. ochengi (748.3 microns x 20.4 microns). All larval stages of O. dukei typically had an attenuated anterior end. The implications of these findings for the epidemiology of human onchocerciasis are discussed. PMID- 1746983 TI - Human cutaneous myiasis due to mixed infestation in a drug addict. AB - Soft tissue infestation by maggots of flies (myiasis) is a well-recognized complication of neglected wounds. Mixed infestation by larvae of more than one species of fly is a rarity. We report, for the first time in India, one such case of cutaneous myiasis due to mixed infestation--in this instance by Chrysomya bezziana and Sarcophaga sp. in a drug addict. PMID- 1746984 TI - Enhancement of virulence of Entamoeba histolytica by in vitro liver treatment. AB - Enhancement of the virulence of five strains of Entamoeba histolytica (three xenically maintained and two axenically maintained) was studied after in vitro incubation with normal hamster liver. Increased virulence was shown by the ability of a small number of liver-treated trophozoites to produce liver lesions in hamsters. Enhancement of virulence was positively correlated with increased resistance to normal hamster serum complement in vitro. PMID- 1746985 TI - Serum cholinesterase levels of vector control workers in Trinidad, West Indies (1979-1987). AB - During 1979-1987 studies were carried out in vitro on the serum cholinesterase levels of 46 vector control workers exposed to insecticides on a daily basis but without clinical manifestations of insecticide poisoning. The results were compared with those of a control group of workers who had not been exposed to insecticides at home or at work. Cholinesterase levels of both groups were determined by a standard colorimetric method. Suppressed serum cholinesterase levels were detected in all 46 workers exposed to insecticides, 25 of whom were aged 30-39 years. Four persons from the control group showed suppressed levels of enzyme; one of these had a genetically low level, and the other three were on medication when the low levels were recorded. PMID- 1746986 TI - Sero-epidemiological studies of cysticercosis in school children from two rural areas of Transkei, South Africa. AB - Anticysticercus antibody titre levels were measured in the sera of 1352 school children from two rural areas of Transkei with different climatic conditions, in the southeastern seaboard of South Africa. The overall seropositivity rate was 5.5%, while the rates for children with good and poor nutritional status were 7.3% and 3.3% respectively. The rates for the two geographical areas did not differ. However, the mean antibody titre level in the 'dry' area (Cofimvaba) with extreme temperature regimes was higher than that in the 'wet' area (Umtata), and well-nourished children from the Cofimvaba area were significantly the most likely to be seropositive. On the other hand, undernourished children from Cofimvaba, and undernourished male children generally, were more likely to be seronegative (Odds Ratio 2.78 and 3.62 respectively). The implications of the findings for the treatment and control of cysticercosis are discussed. PMID- 1746987 TI - Sodium azide: ineffective as a faecal preservative for parasitological diagnosis. AB - Sodium azide was compared with 10% formalin to evaluate sodium azide's effectiveness as a faecal preservative for intestinal helminths and protozoa. Faecal specimens collected from Haiti were preserved in sodium azide and in 10% formalin and analysed after 1.5, 6.5 and 11.5 weeks by examining direct wet-mount preparations. Sodium azide did not preserve the morphology of either helminths or protozoa as well as 10% formalin did. However, sodium azide prevented embryogenesis of helminth eggs, while some helminth eggs in 10% formalin contained living larvae. Biosafety guidelines regarding the toxicity, reactivity, and disposal of sodium azide were strictly followed. Use of 10% formalin is a significantly better choice than sodium azide for preserving parasites when accurate identification of parasites and biosafety are the main concerns. PMID- 1746988 TI - Bacterial infection of hydatid cyst following albendazole treatment. PMID- 1746989 TI - Immunological diagnosis of amoebic liver abscess. PMID- 1746990 TI - Calcium antagonists and diabetic nephropathy. PMID- 1746991 TI - Medical therapy for gastroesophageal reflux disease. Not all treatments are equal! PMID- 1746992 TI - A perspective on converting enzyme inhibitors and calcium channel antagonists in diabetic renal disease. AB - Hypertension and renal disease are major causes of morbidity and mortality in the diabetic population, with the presence of microalbuminuria established as a predictor of excess mortality. Numerous attempts, both pharmacologic and nonpharmacologic, have been made to intervene in the disease process. Experimental and clinical evidence suggests that the converting enzyme inhibitors and, more recently, certain calcium antagonists have beneficial effects on renal function above and beyond those simply due to blood pressure control. These effects are likely attributable to favorable systemic and renal hemodynamic changes as well as to direct cellular effects. However, intervention with these agents in various rat models of diabetes or hypertension is initiated very early. Hence, some of the beneficial renal effects may not be as dramatic in clinical practice because of the more commonly advanced stage seen at the time of intervention. We present an overview of the histologic, renal hemodynamic, and antiproteinuric effects of these agents in the experimental setting, as well as the clinical evidence supporting the use of angiotensin-converting enzyme inhibitors and certain classes of calcium antagonists in diabetic renal disease. PMID- 1746993 TI - Silent myocardial ischemia. A clinical perspective. AB - Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis. PMID- 1746994 TI - Hepatic hydrothorax. Cause and management. AB - Significant pleural effusions are infrequently noted in patients with cirrhosis of the liver. A large effusion (hepatic hydrothorax) occasionally appears during the course of the disease. The fluid in the pleural space is believed to be derived from ascitic fluid that may accompany hepatic cirrhosis. Although the exact mechanism is somewhat controversial, it appears that the ascitic fluid is transported directly into the pleural space. A therapeutic thoracentesis, usually accompanied by a paracentesis, may be necessary to relieve acute symptoms. Long term management, however, centers around eliminating or reducing the formation of ascites. When this is not successful, tube thoracostomy followed by chemical pleurodesis, primary repair of diaphragmatic defects with pleural sclerosis, or peritoneovenous shunting in conjunction with chemical pleurodesis may be attempted. These interventions may or may not be successful. Management of hepatic hydrothorax remains a clinical challenge. PMID- 1746995 TI - Raynaud's phenomenon. The French tricolor. AB - Recent epidemiologic surveys indicate that episodic vasospasm of arterioles (Raynaud's phenomenon) is a common finding in the general population. In a small minority of these individuals, an underlying, often reversible cause or systemic disease associated with vasospasm can be identified. The range of these so-called secondary forms of vasospasm is broad and includes systemic rheumatic syndromes, vibration-induced vascular injury, drug-induced vasospasm, and infectious disorders. Several different physiologic mechanisms may be responsible for vasospasm; hyperactivity of the sympathetic nervous system and abnormal adrenergic receptor function appear to be most important. PMID- 1746996 TI - Famotidine relieves symptoms of gastroesophageal reflux disease and heals erosions and ulcerations. Results of a multicenter, placebo-controlled, dose ranging study. USA Merck Gastroesophageal Reflux Disease Study Group. AB - We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose. PMID- 1746997 TI - The impact of diuretic therapy on reported sexual function. AB - BACKGROUND: --Thiazide diuretics are the most commonly prescribed antihypertensive agent in the treatment of hypertension. No studies to date have isolated conclusively the effect of diuretic therapy on patient quality of life, and particularly on sexual dysfunction. METHODS: --We carried out a randomized placebo-controlled trial of the effect of thiazide diuretics on quality of life in mildly hypertensive men between the ages of 35 and 70 years. After a 1-month washout period off diuretic therapy, the men were randomized to a 2-month trial of a thiazide treatment or placebo. At the end of the trial, 176 men completed a confidential self-administered questionnaire assessing aspects of social performance, general well-being, and emotional and physiologic states. RESULTS: - Patients taking diuretics reported significantly greater sexual dysfunction than control subjects, including decreased libido, difficulty in gaining and maintaining an erection, and difficulty with ejaculation. Multivariate analysis suggested that the findings were not mediated by low serum potassium levels or by low blood pressure. Sexual dysfunction was noted more often in the confidential self-report questionnaire than in response to direct questions from clinicians. We found no differences between diuretic and placebo groups in measures of mood, general sense of well-being, ability to work, alertness, and social/recreational activities. CONCLUSIONS: --Thiazide diuretic use is associated with male sexual dysfunction but does not appear to adversely affect other aspects of quality of life. PMID- 1746998 TI - The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope. AB - Adenosine appears to be an important mediator of hypotension and bradycardia in certain subsets of patients with vasodepressor syncope. Adenosine receptor blockage with methylxanthines may hypothetically prevent the vasodepressor spell. We studied the chronotropic, hemodynamic, and cardiac autonomic responses to head up tilt in patients (mean age 40.7 +/- 18.1 years) with vasodepressor syncope before and after treatment with oral theophylline. At baseline, hypotension and syncope or near syncope were induced at 11.7 +/- 2.3 minutes of 60 degrees head up tilt in all patients. Cardiac vagal and sympathetic tone showed biphasic and directionally opposite changes during tilt. Repeat tilt during oral theophylline therapy (6-12 mg/kg/day for 14 +/- 6 days) did not provoke symptomatic hypotension in 82% of patients. During 10.7 +/- 6.1 months of follow-up, seven patients had no recurrence of vasodepressor syncope and seven patients discontinued theophylline because of adverse reactions. Low-dose theophylline prevents tilt-induced vasodepressor syncope and may prevent spontaneous vasodepressor syncope in selected patients who can tolerate theophylline. PMID- 1746999 TI - Primary pulmonary hypertension in the elderly. AB - Primary pulmonary hypertension is usually considered a disease of younger adults. We reviewed the natural course of primary pulmonary hypertension in patients aged 65 years or greater. During an 8-year period, 63 elderly patients were discharged from our hospital with a diagnosis of pulmonary hypertension. In eight instances, an elevated mean pulmonary arterial pressure (greater than 25 mm Hg) could not be explained by secondary causes. These elderly patients with primary pulmonary hypertension had symptoms common to younger patients with this disease, including dyspnea (eight patients), chest pain (five), pedal edema (four), and fatigue (one). In all but one patient, the initial diagnosis was incorrect, and the patients were thought to have more common diseases of the elderly that cause similar symptoms. Coexisting medical problems were common and further obscured the correct diagnosis. Survival was significantly shorter in those patients with symptoms of less than 6 months' duration. Primary pulmonary hypertension should be considered in the differential diagnosis in elderly patients with unexplained dyspnea and chest pain. PMID- 1747000 TI - High frequency of human immunodeficiency virus-associated autonomic neuropathy and more severe involvement in advanced stages of human immunodeficiency virus disease. AB - We conducted a controlled trial to determine frequency and severity of autonomic neuropathy in patients infected with the human immunodeficiency virus (HIV). We studied 25 HIV-seropositive patients and 10 seronegative controls in HIV risk groups by means of five cardiovascular tests, and autonomic neuropathy was graded with a scoring system. The overall autonomic test score differed between patients and controls and was higher in patients with advanced (Centers for Disease Control class IV) disease than in those with earlier (class II or III) HIV disease. Of the patients, 60% had findings of autonomic dysfunction. Our data demonstrate a high prevalence of autonomic neuropathy in HIV-infected patients. Advanced HIV disease is associated with more severe involvement than earlier disease states. PMID- 1747001 TI - Decrease in reported posttransfusion hepatitis. Contributions of donor screening for alanine aminotransferase and antibodies to hepatitis B core antigen and changes in the general population. AB - Blood donor screening for hepatitis B core antibody and elevation of serum alanine aminotransferase level, surrogate markers of hepatitis C/non-A, non-B (NANB) infection, was implemented in 1986. Reported cases of posttransfusion hepatitis (PTH) from 1985 to 1988 were reviewed to ascertain the effect of surrogate testing on the number and character of cases and to compare any changes with those in the incidence of hepatitis in the general population. The reports of all PTH, NANB PTH, and type B PTH decreased 61.5%, 75.4%, and 84.5%, respectively. The rates of reported cases of NANB hepatitis and hepatitis B in the general community also fell during the period of review. The decrease in PTH and background hepatitis was similar between 1985 and 1986. In 1987, the first complete year of surrogate testing, the incidence of PTH decreased at a greater rate, to levels 50% below what would have been projected on the basis of background changes alone for NANB PTH, and to 35% below projected for type B PTH. There appears to have been a substantial decrease in the risk of both type B PTH and NANB PTH in the northeastern United States between 1985 and 1988 due to a combined effect of donor surrogate testing and a decrease in the background rates of hepatitis in the donor population. PMID- 1747002 TI - A reappraisal of the causes of hemoptysis. AB - We reviewed the records of 264 patients who underwent fiberoptic bronchoscopy for unexplained hemoptysis to determine the various causes of hemoptysis. Bronchogenic carcinoma (29%), bronchitis (23%), and idiopathic hemoptysis (22%) accounted for the majority of causes of hemoptysis. In contrast to older studies, the incidence of hemoptysis secondary to tuberculosis and bronchiectasis has decreased. Although our patient population is predominantly male and elderly, our data may well be representative of more recent epidemiologic trends in causes of hemoptysis. PMID- 1747003 TI - The provision of physical activity to hospitalized elderly patients. AB - Physical activity has been recognized as an important aspect of patient care for nearly 50 years. Yet, deconditioning and functional decline of hospitalized elderly patients continue to be reported. Such outcomes suggest that a good system for providing activity in hospitals is lacking. In this retrospective study we assessed the provision of physical activity to 500 elderly patients (100 in each of five hospitals) during the first 7 days of hospitalization. No activity order was in effect on 13% of the 3500 patient days reviewed. When activity was ordered, patient activity was different from the activity permitted by the physician orders on 41% of the days. Patients who remained in bed or in a chair rarely received physical therapy, never had physician orders for exercises, and never performed exercises with the nurses. These findings demonstrate that the current practices for the provision of physical activity in hospitals are ineffective. PMID- 1747005 TI - What should house officers know about medical ethics? PMID- 1747004 TI - Thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. Randomized, double-blind, placebo-controlled study of 100-mg oral fluconazole daily. AB - Recurrent oropharyngeal candidiasis is common in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. It causes local pain and discomfort, loss of taste, and aversion to food and may lead to secondary complications. We examined, in a double-blind study, whether recurrent thrush could be prevented by prophylaxis. Twenty-five patients with one to four previous thrush episodes who had no thrush at the outset of the study were randomized to receive 100 mg of fluconazole or placebo daily for 12 weeks. If thrush occurred, prophylaxis was stopped and patients were treated conventionally, after which prophylaxis was resumed. After the randomized study, some patients were given continuous fluconazole (open phase). In the randomized study, thrush occurred in eight of 13 placebo-treated patients and none of 12 fluconazole-treated patients. Possible side effects were not different between the groups. Dermatophytosis and onychomycosis and cryptococcuria also improved in the fluconazole-treated patients, and fungal colonization was significantly decreased. One episode of thrush occurred in the open phase in an intermittently compliant patient (group total, 71.5 patient-months of fluconazole treatment); in contrast, the 25 patients also had had two episodes of Candida esophagitis, three of cryptococcosis, and 13 of dermatophytosis before entry. Subsequent to entry in the randomized trial, in 92.3 patient-months without fluconazole, there were 35 episodes of thrush, one of esophagitis, one of cryptococcemia, and one of dermatophytosis, and preexisting dermatophytosis and onychomycosis were unchanged or worsened. Individual patients observed with and without fluconazole treatment also showed its efficacy. In conclusion, thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome related complex with negligible toxic effects. Larger trials to confirm prevention of all mycoses with prophylaxis should be considered. PMID- 1747007 TI - Categories of patients with gastroesophageal reflux. PMID- 1747006 TI - Pneumothorax following feeding tube placement. PMID- 1747008 TI - Decision analysis for isoniazid chemoprophylaxis. PMID- 1747009 TI - Respiratory syncytial virus pneumonia in hospitalized adults. PMID- 1747010 TI - Health promotion and nurses. PMID- 1747011 TI - Drug interaction with quinolone antibiotics in intensive care unit patients. PMID- 1747012 TI - Sonography-guided thoracentesis. PMID- 1747013 TI - Which categories of patients are known to benefit from aspirin? PMID- 1747014 TI - Hippocampal neuron number in schizophrenia. A stereological study. AB - Neuropathologic and neuroradiologic studies have reported hippocampal abnormalities in schizophrenics. We estimated the total number of neurons in the hippocampus of schizophrenics and controls to elucidate the neuronal basis of such changes. Thirteen brains of schizophrenics and 13 control brains closely matched for sex and age were studied. A new stereological method was applied to serial coronal sections through the whole hippocampus. Total hippocampal volume was reduced in the schizophrenic sample, more pronounced on the left side, but mean differences were not significant. The volumes of the pyramidal cell layer in the four subdivisions subiculum and cornu Ammonis sectors CA 1, CA 2/3, and CA 4 were almost identical in both groups. Schizophrenics did not differ from controls with regard to nerve cell density in any of the four subdivisions. The estimates of the total number of neurons in the hippocampal subdivisions were not different between schizophrenics and controls. The data do not support the hypothesis that hippocampal abnormalities are caused by neuronal cell loss. However, they are consistent with the suggestion that white matter changes in the hippocampus may play a role in the pathogenesis of schizophrenia. PMID- 1747015 TI - Alterations in Alzheimer's disease-associated protein in Alzheimer's disease frontal and temporal cortex. AB - Alzheimer's disease (AD)-associated protein is present in brain and cerebrospinal fluid of patients with AD but not in adult, nondemented, normal controls. This protein may represent an abnormal epitope of the "tau" microtubule-associated protein and has been detected before the appearance of senile plaques and neurofibrillary tangles. The amount of AD-associated protein in the frontal and temporal cortices in 93 cases of neuropathologically confirmed AD was compared with the amount that was present in 20 cases without AD. The amount of AD associated protein was significantly increased in the cases of AD for both brain regions compared with that in the cases without AD. The presence of high levels of this protein is a useful adjunct, postmortem marker of the presence of AD and may eventually lead to tests that allow early detection of individuals at risk for this disease. PMID- 1747016 TI - Brain anatomic effects of electroconvulsive therapy. A prospective magnetic resonance imaging study. AB - To determine prospectively whether electroconvulsive therapy (ECT) produces structural brain changes, 35 inpatients with depression underwent magnetic resonance imaging before and twice after (at 2 to 3 days and at 6 months) completion of a course of brief-pulse, bilateral ECT. The magnetic resonance images were analyzed blindly for evidence of changes in brain structure using two approaches: measurement of regional brain volumes and a pairwise global comparison. Structural brain abnormalities were present in many patients before ECT. The course of ECT produced no acute or delayed (6-month) change in brain structure as measured by alterations of the total volumes of the lateral ventricles, the third ventricle, the frontal lobes, the temporal lobes, or the amygdala-hippocampal complex. In five subjects, the pairwise global comparisons revealed an apparent increase in subcortical hyperintensity, most likely secondary to progression of ongoing cerebrovascular disease during follow-up. Our results confirm and extend previous imaging studies that also found no relationship between ECT and brain damage. PMID- 1747017 TI - Volunteers for biomedical research. Recruitment and screening of normal controls. AB - We examined the process of accruing healthy control subjects for biomedical research on brain function. Of 1670 responders to newspaper advertising, 23.1% were uninterested when learning more about the studies, and 50.9% of those remaining were found by structured telephone screening to meet exclusionary criteria for having a history of psychiatric, neurologic, or medical disease that might affect brain function. Of 312 volunteers passing the telephone screening who came to an in-person evaluation by a physician and agreed to participate, 49.7% were found to meet exclusionary criteria, and only 157 were admitted to the study. This underscores the importance of attending to the issue of screening and assessment of "normal volunteers." Alternative strategies should be considered for enriching the pool. PMID- 1747018 TI - The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. PMID- 1747019 TI - Genetic factors in stuttering confirmed. PMID- 1747020 TI - Natural history of schizophrenia subtypes. I. Longitudinal study of paranoid, hebephrenic, and undifferentiated schizophrenia. AB - To explore the validity of different approaches for subtyping schizophrenia, the conditions of 187 schizophrenic patients from the Chestnut Lodge follow-up study were rediagnosed with the use of classic subtype criteria. Independently collected data allowed construction of a longitudinal profile of the natural history of illness for patients who met operational criteria for paranoid (n = 78), hebephrenic (n = 26), and undifferentiated (n = 83) schizophrenia. Paranoid schizophrenia had an older age at onset, often developed rapidly in individuals with good premorbid functioning, tended to be intermittent during the first 5 years of illness, and was most associated with good outcome or recovery. Hebephrenia had an earlier age at onset, often developed insidiously, and was associated with a greater family history of psychopathology, poor premorbid functioning, and, frequently, a continuous illness with a poor long-term prognosis. While also early and insidious in onset, unlike hebephrenia, undifferentiated schizophrenia was poorly distinguished from the patients' premorbid state, associated with an early history of behavioral difficulties, and often resulted in a continuous but stable disability. We discuss implications for nosology. Although distinctive patterns were discernible, the considerable heterogeneity within subtypes calls for continued efforts to develop and explore alternate classification schemes. PMID- 1747021 TI - Natural history of schizophrenia subtypes. II. Positive and negative symptoms and long-term course. AB - The natural history and long-term course of schizophrenia divided by pervasiveness of positive and negative symptoms was explored among 187 schizophrenic patients from the Chestnut Lodge follow-up study. Schizophrenia with many negative symptoms was associated with poor premorbid functioning, insidious onset, partial or no remissions during the first several years of illness, and in most cases a progressive course leading to permanent disability. Schizophrenia with few negative symptoms was associated with good premorbid functioning, acute onset, intermittent early course, and a better prognosis. Positive symptoms predicted future hospitalizations but were less powerful and specific as indicators of differential illness history, course, and long-term functional incapacity. As predictors of long-term outcome, negative symptoms were of greater value measured at index admission several years after illness onset than at first hospital admission. Multivariate analyses indicated that two negative symptoms (anhedonia and affective flattening) contribute significantly to outcome variance independent of their association with premorbid functioning or positive symptoms. Patients with the poorest long-term outcome tended to show an increase in negative symptoms during the early years of their illness. Progressive negative symptoms early in the course of schizophrenia may thus reflect or signal a process leading to long-term functional disability. PMID- 1747022 TI - Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform disorder. A regional cerebral blood flow study. AB - To measure prefrontal and subcortical activity during a cognitive task, we examined 19 newly diagnosed schizophrenics and patients with schizophreniform psychosis. Seven healthy volunteers served as controls. The patients were drug naive or had received neuroleptics for a few days only. Cerebral blood flow distribution was depicted by single photon emission computed tomography at rest and during activation with the Wisconsin Card Sorting Test. A significant relative activation deficit in the left inferior-prefrontal region was revealed during the Wisconsin Card Sorting Test in the patient group. Furthermore, the patients had impaired striatal suppression on the left side during the cognitive task. The test performance was significantly impaired in the patients. The inability to reduce striatal activity may be due to a lack of corticostriatal feedback during prefrontal activation. PMID- 1747024 TI - Papillary endothelial hyperplasia in the thyroid. PMID- 1747023 TI - Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. AB - A recent report suggested that neurons in the prefrontal, anterior cingulate, and primary motor cortex of the brains of schizophrenic subjects may be less dense than those in the brains of nonschizophrenic subjects. We have determined whether pyramidal neurons and/or interneurons are preferentially reduced in schizophrenic subjects. Twelve control subjects and 18 schizophrenic subjects were studied in a blind, quantitative analysis of the density of pyramidal cells, interneurons, and glial cells in each of the six layers of the anterior cingulate and prefrontal cortex. The results showed that numbers of small neurons (interneurons) were reduced in most layers of the cingulate cortex in schizophrenic subjects compared with nonschizophrenic subjects, with the differences being greatest in layer II. In the prefrontal area, interneuronal density was also lower in layer II and, to a lesser extent, in layer I in schizophrenic subjects compared with control subjects. In most cases, the differences were similar, although more significant, in schizophrenic subjects who had had superimposed mood disturbances than in schizophrenic subjects who had not had such comorbidity. Numbers of pyramidal neurons generally were not different between control and schizophrenic subjects, except in layer V of the prefrontal area, where schizophrenic subjects showed higher densities of these neurons. Glial numbers did not differ between the control and schizophrenic subjects, suggesting that a neurodegenerative process did not cause the reduced interneuronal density observed. Using multiple regression analysis and analysis of covariance, decreases in the density of layer II interneurons could not be adequately explained by the effects of various confounding variables, such as age, postmortem interval, duration of specimen fixation, or administration of neuroleptic agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747025 TI - Reducing the number of routine preoperative screening bleeding time tests. PMID- 1747026 TI - Quality of laboratory performance in testing for human immunodeficiency virus type 1 antibody. Variables associated in multivariate analyses. AB - In May 1988, the Centers for Disease Control's Model Performance Evaluation Program (Atlanta, Ga) surveyed 1092 laboratories that performed enzyme immunoassays and Western blot tests for human immunodeficiency virus type 1 antibody on mailed plasma samples of known human immunodeficiency virus type 1 antibody reactivity and that described their laboratory characteristics and testing practices. The study objective was to evaluate the quality of laboratory performance in testing for human immunodeficiency virus type 1 antibody. After identifying relevant variables in univariate analyses, multivariate analyses were performed using stepwise logistic models. Human immunodeficiency virus type 1 antibody test performance was independently associated with analytic variables such as commercial test kit used and with nonanalytic variables such as experience, training, and degree requirements of laboratory personnel. These results validate the importance of nonanalytic variables to the quality of outcomes in laboratory testing. PMID- 1747027 TI - Recruitment of pathology trainees. Recent trends from the 1989 Association of Pathology Chairmen's Survey of first-year pathology residents. AB - The evolving pathology manpower shortage requires that we examine recruitment issues closely. We present data from the 1989 Association of Pathology Chairmen residents' questionnaire and analyze the most important recruitment patterns. Of 685 first-year pathology residents in 1989, 451 (66%) responded to the survey. When compared with other specialties, 1989 pathology residents are older (mean age, 30.1 years), more frequently women (38%), more often foreign medical graduates (23%), and more commonly have MD/PhD degrees (7.8%). Among pathology residents, the fifth year of required training is the most important negative factor in choosing pathology. Over 50% of 1989 first-year pathology residents changed their mind about another specialty to enter pathology; 37% chose pathology only after graduating from medical school. In 1988 and 1989, 63% of first-year pathology residents responding to the Association of Pathology Chairmen residents' questionnaire indicated that role models were an important factor in their specialty choice. The most typical role model was a male pathologist, approximately 47 to 48 years old. Role model influence tended to be greater for those residents who decided to enter pathology earlier in medical school. Nevertheless, over 50% of those residents who decided to enter pathology after medical school claimed that role model influence was important in their choice. Role models remain a valuable resource for improved recruitment into pathology. PMID- 1747028 TI - How can hospital autopsy rates be increased? AB - Autopsy studies have provided the foundation of our knowledge of clinical medicine. Despite the acknowledged value of this postmortem procedure, hospital autopsy rates have fallen to only 10% of deaths. New diseases and therapeutic modalities are in danger of not being properly evaluated. A number of proposals have been made to increase autopsy rates. While many of these proposals are excellent, the key to increasing autopsy rates is direct reimbursement by third party payers. PMID- 1747029 TI - The neuropathology of human immunodeficiency virus infection. The Dallas, Texas, experience. AB - Postmortem neuropathologic changes were evaluated in 141 consecutive patients dying with human immunodeficiency virus infection at publicly supported hospitals affiliated with the University of Texas Southwestern Medical Center in Dallas, between August 1984 and September 1990. Morphologic abnormalities were identified in 112 cases (79%). Cytomegalovirus was the most common opportunistic infection encountered, with characteristic viral inclusions identified in 23 patients, and presumptive evidence of infection in six additional patients. Progressive multifocal leukoencephalopathy was present in four patients. Gram-positive bacterial infections were identified in six patients, and mycobacterial infections in three patients. Opportunistic fungal infections included cryptococcosis (13 cases), histoplasmosis (two cases), and coccidioidomycosis (one case). Toxoplasmosis was uncommon, with active or quiescent lesions identified in five patients. Lymphoma was present in nine patients and was primary in the central nervous system in five patients. Multinucleate giant cell (human immunodeficiency virus) encephalitis was identified in 28 patients. In an additional 26 patients, microglial nodules and/or more generalized white-matter abnormalities were encountered in the absence of multinucleate giant cells, cytomegalovirus inclusions, or systemic cytomegalovirus infection. Vacuolar change was present in 21% of spinal cords, and was highly correlated with cytomegalovirus infection in the nervous system. Mixed infections and/or neoplasms were identified in 24 patients. This survey documents a high frequency of neuropathologic abnormalities in human immunodeficiency virus-infected individuals in a geographical region of the United States not represented in previous series. Variations noted in the frequencies of specific central nervous system disorders between this and other study populations reinforce the need for continuing documentation of geographical trends in human immunodeficiency virus associated disorders. PMID- 1747030 TI - Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome. AB - In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection. PMID- 1747031 TI - Blastomycosis and opportunistic infections in patients with acquired immunodeficiency syndrome. An autopsy study. AB - Patients with acquired immunodeficiency syndrome (AIDS) are subject to a host of opportunistic infections, but to our knowledge a predisposition to blastomycosis has not previously been established. Autopsies of two patients with AIDS revealed disseminated blastomycosis with massive pulmonary involvement, Blastomyces meningoencephalitis, and widespread dissemination. The massive systemic involvement and rapid terminal course in both cases may reflect the state of acquired immunodeficiency. An analysis of an autopsy series showed that the incidence of blastomycosis was increased in patients with AIDS, although some other opportunistic organisms were more common (eg, Pneumocystis carinii, Mycobacterium avium-intracellulare, and Candida species). Thus, the diagnosis and treatment of blastomycosis must be pursued in patients with AIDS. Additional data are needed to further determine the incidence of blastomycosis in the population of patients with AIDS. PMID- 1747032 TI - Disseminated pneumocystosis without pulmonary involvement during prophylactic aerosolized pentamidine therapy in a patient with the acquired immunodeficiency syndrome. AB - Pneumocystosis, the most common opportunistic infection associated with the acquired immunodeficiency syndrome, is usually restricted to the lungs and results in severe bilateral pneumonia, which is fatal unless vigorously treated. Rare cases have been reported in which involvement of other organs or disseminated disease occurred in addition to the pulmonary lesions. Pentamidine, an efficient drug used intravenously for the treatment of pulmonary pneumocystosis, has also recently been used in aerosolized form for the prevention of Pneumocystis infection in patients with the acquired immunodeficiency syndrome. In the present case, widely disseminated, though symptomless, pneumocystosis developed in a human immunodeficiency virus-positive individual treated prophylactically with aerosolized pentamidine. Despite heavy multiorgan infection with Pneumocystis carinii, the lungs revealed no microorganisms or characteristic inflammatory lesions. This case indicates that aerosolized pentamidine, while efficient against the pulmonary infection, may not produce fungicidal blood levels sufficient for the prevention of disseminated pneumocystosis. PMID- 1747033 TI - Herpes simplex virus infection of the placenta. The role of molecular pathology in the diagnosis of viral infection of placental-associated tissues. AB - Herpes simplex infections of the placenta and its associated tissues are rarely seen and, consequently, the pathologic features are not well understood. We describe the occurrence of herpes simplex virus infection of the placenta that was limited to maternal-derived cells of the subchorionic tissue. The microscopic findings were remarkable for both the absence of inflammation and characteristic viral inclusions. However, in situ DNA hybridization, as well as immunohistochemistry using antibody to herpes simplex virus type 2, revealed herpes virus infection of decidualized cells in the decidua capsularis. The significance of this finding, and the importance of molecular techniques for the diagnosis of herpes virus infection in placental pathology, are discussed. PMID- 1747034 TI - Human immunodeficiency virus-related Kaposi's sarcoma of the appendix and acute appendicitis. Report of a case and review of the literature. AB - We describe a case of acute appendicitis precipitated by human immunodeficiency virus-related Kaposi's sarcoma of the appendix. This presentation in an otherwise asymptomatic homosexual man led to the establishment of a diagnosis of acquired immunodeficiency syndrome. Immediate follow-up revealed multicentric gastrointestinal involvement by Kaposi's sarcoma, and skin involvement ensued in 2 months. Salient features of this case and two other similar reports in the literature are highlighted. PMID- 1747035 TI - Respiratory and enteric cryptosporidiosis in humans. AB - A 24-year-old homosexual man with acquired immunodeficiency syndrome presented with intractable diarrhea and fever. Examination of a rectal biopsy specimen and stool revealed Cryptosporidium. Approximately 4 months after admission he developed respiratory failure and died. Postmortem examination revealed cryptosporidiosis involving the entire gastrointestinal tract as well as the tracheobronchial tree. To our knowledge, this is one of the rare presented cases of tracheobronchial cryptosporidiosis documented histologically. PMID- 1747036 TI - Lymphadenopathic tumor exhibiting intermingled features of Kaposi's sarcoma, malignant lymphoma, and angiofollicular hyperplasia. AB - A 56-year-old man presented with an inguinal lymph node enlargement. Histologic study of the tumor revealed three intermingled pathologic lesions: a nodular small cell lymphoma, an angiofollicular hyperplasia of vasculohyaline type, and a vascular neoplasia closely resembling Kaposi's sarcoma. The patient was immunocompetent and denied any homosexual relationships, transfusions, or drug use. The serum was negative for the presence of human immunodeficiency virus antibody. Computed tomographic scan and ultrasound examination revealed no other lymphadenopathies. This case shows that both hyperplastic and neoplastic lymphoid proliferations can occur simultaneously with vascular neoplasia. It thereby suggests that the neoplastic populations might interact to favor the tumor growth, the sequence and the nature of the stimulating events remaining unclear. PMID- 1747037 TI - Pseudofungi in a lymph node. A case report with energy dispersive X-ray elemental analysis. AB - A case of pseudofungi in axillary lymph nodes is presented. They resembled septate hyphae and were stained with a periodic acid-Schiff stain. Gomori methenamine silver stain failed to stain them. Because of morphologic similarity to true septate fungi and positive staining with periodic acid-Schiff stain, these structures can be misinterpreted as septate hyphae forming true fungal organisms. Further studies, some of which included energy-dispersive x-ray elemental analysis and special stains, revealed that they were composed of iron, phosphorus, and calcium. The relationship of these pseudofungi to previously published cases and clues that enable one to make a correct diagnosis are described. PMID- 1747038 TI - Urethral T-cell lymphoma as the initial manifestation of the acquired immune deficiency syndrome. AB - We report the first case (to our knowledge) of a primary urethral T-cell lymphoma as the initial manifestation of the acquired immune deficiency syndrome. A 36 year-old white homosexual man with antibodies to human immunodeficiency virus type 1 was evaluated for a hemorrhagic urethral discharge. A 2-cm fleshy, polypoid mass in the bulbous urethra was removed, and the diagnosis of small non cleaved cell (non-Burkitt's) lymphoma was made. Immunohistochemical analysis confirmed that the tumor was of T-cell lineage. Patients with the acquired immunodeficiency syndrome have an increased incidence of lymphomas, particularly extranodal high-grade non-Hodgkin's lymphomas. Primary urethral lymphomas are extremely rare, with only a handful of cases reported in the literature. This rare form and site of lymphoma should be considered in patients with the acquired immunodeficiency syndrome who have genitourinary symptoms. PMID- 1747039 TI - The attitudes of second- and third-year medical students to the autopsy. A survey by postal questionnaire. AB - Questionnaires were mailed to medical students in the cohorts who had just completed the second and third years of their courses. These included 52 attitude statements to which students indicated their responses on five-point Likert scales. Significant differences were found between the responses of the two cohorts to 18 statements. The results indicate a good general acceptance of the principle of autopsy in both groups, but the senior cohort was more reluctant to become personally involved, despite being more aware of the value of the autopsy in clinical audit, more aware that the autopsy has nonforensic uses, and more aware that autopsies remain useful in elderly subjects. Additionally, they were considerably less likely to want autopsies on close relatives. PMID- 1747040 TI - Self-reports of "positive" childhood and adolescent sexual contacts with older persons: an exploratory study. AB - An exploratory, descriptive study of 37 male and 26 female subjects reporting childhood or adolescent intergenerational sexual contacts about which subjects maintained, at least in part, "positive" feelings is reported. An informal comparison group of 7 female victims of sexual abuse also participated. Subjects were administered a 21-page, 130-item questionnaire designed to explore and evaluate childhood functioning and development, the nature of the sexual experience, and its possible impact on adult life. Eight subjects also participated in subsequent in-depth telephone interviews. A wide range of characteristics and possible effects of the experiences were reported, suggesting that intergenerational sexual contacts may represent a continuum of experience rather than a unitary and discrete pathological phenomenon. PMID- 1747041 TI - Development of male gender identity/role and a sexual orientation towards women in a 46,XY subject with an incomplete form of the androgen insensitivity syndrome. AB - Transsexualism and homosexuality have been theorized to originate in the male from insufficient androgenization of the brain. For verification of this hypothesis clinical science must rely on subjects with an abnormal prenatal/perinatal endocrine history. A case of a 33-year-old 46,XY subject with an incomplete form of androgen insensitivity syndrome (AIS) is presented. In adulthood the only genital sign of masculinization is a clitoris of 4 cm; the vagina is normal size. The diagnosis AIS was verified by androgen receptor studies. At birth there was confusion as to the sex of the newborn. Originally, the subject was assigned to the male sex, but this decision was reversed 5 days after birth and the subject was reared as a girl. At age 30 the subject applied for gender reassignment treatment to the male sex. Upon psychological evaluation the gender identity was unambiguously male and the sexual orientation was exclusively towards women. The estrogen feedback effect on LH, regarded by some as a marker of the sexual differentiation of the neuroendocrinium was negative before orchiectomy but positive after orchiectomy. Our observation demonstrates that in 46,XY subjects a male gender identity and a sexual orientation towards women can develop with a strikingly lower-than-normal level of biological action of androgens. PMID- 1747042 TI - Examining predictors of sex guilt in multiethnic samples of women. AB - Previous research has shown that attitudes, including sex guilt, may influence the nature and type of sexual practices in which a person engages. This study examined the relationship of socioeconomic status (SES), ethnicity, and religiosity to sex guilt and aspects of sexual permissiveness that relate to sexual attitudes. Subjects were random samples of 126 African American women and 122 white American women in Los Angeles County. They were interviewed face-to face and completed the Mosher Forced Choice Sex Guilt subscale. Results indicated that while the association between church attendance and sex guilt was stronger for white than for black women, no significant differences in sex guilt across attendance levels was found for black women. Overall, contrary to previous reports, black women had higher levels of sex guilt than their white peers. The importance of understanding factors including SES and religiosity as they relate to African American and white American women's sexual attitudes and behaviors is discussed. PMID- 1747043 TI - Homosexual mounting in free-ranging female Hanuman langurs (Presbytis entellus). AB - Female-female mounting was studied for 3233 hr in a bisexual one-male troop of free-ranging Hanuman langurs in northwestern India over a period of 6 years. The population breeds throughout the year and female-female mounts (n = 524) occurred during all months. All 15 adult females mounted and were mounted, although only 20% of the individuals exhibited more than half of all mounter activity and 33% more than half of all mountee activity. Various similarities with heterosexual mounting suggest that sexual arousal is a stimulus of the activity. Cycling, pregnant, and lactating females acted as mounters as well as mountees. However, ovulating individuals were greatly overrepresented concerning their likelihood of mounting and being mounted. Females of any given rank in the dominance hierarchy showed mounter as well as mountee activity, although mounters were higher ranking than mountees in 84% of cases. Young mounters were overrepresented and middle- to old-aged mounters underrepresented, whereas no such differences existed for mountees. Mounting relations among four young adult paternal half-sisters who occupied top positions in the dominance hierarchy were significantly overrepresented. Although the ultimate function of homosexual female mounting is not fully understood, it is suspected to be connected with intrasexual competition: If "pseudocopulations" induce mountees to reduce the number of solicitations addressed to the male, the probability of insemination decreases and mounters thus reduce the number of future competitors. PMID- 1747044 TI - Who speaks for general surgery? PMID- 1747045 TI - The demise of general surgery: deja vu. PMID- 1747046 TI - Total axillary lymphadenectomy in the management of breast cancer. AB - The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided. PMID- 1747047 TI - Breast biopsy techniques and adequacy of margins. AB - The change toward breast-conserving surgery for cancer has altered the role of the initial biopsy. We retrospectively analyzed two methods, traditional excisional biopsy (n = 47) and lumpectomy (n = 44) to evaluate their usefulness as the initial procedure for breast-conserving surgery. Lumpectomy required more time (mean +/- SEM, 53 +/- 3 minutes) than traditional biopsy (37 +/- 2 minutes). Margins were verified by microscopic examination to be clear in 73% of the patients in the lumpectomy group and in only 17% of patients in the traditional biopsy group. Patients in the lumpectomy group subsequently underwent more axillary dissections than patients in the traditional biopsy group (31% vs 4%, respectively) and fewer modified radical mastectomies (49% vs 71%, respectively). A correlation between extensive intraductal components and positive margins was found in the lumpectomy group. These data suggest that as the initial biopsy method, lumpectomy more often provides adequate margins and may decrease the number of subsequent procedures on the breast for breast-conserving surgery. PMID- 1747048 TI - Malignant melanoma in black Americans. A trend toward improved survival. AB - A search of patients seen at the Duke University Melanoma Clinic (Durham, NC) identified 79 black patients. Five- and 10-year survival was 35% and 26%, respectively. Patients presenting in the recent decade had less advanced disease, resulting in an improved 5-year survival of 49%. Five-year survival for white patients was 74%. Black patients had more negative prognostic indicators when compared with white patients. In a multivariate analysis, however, race was not a prognostic indicator, suggesting melanoma is not inherently more aggressive in black patients. The trend during the past decade has been for black patients to present with less advanced disease, with improved survival. This may be related to better appreciation of the disease by patients and physicians alike. Continued emphasis on education and early diagnosis may result in further improvement for black patients with melanoma. PMID- 1747049 TI - A prospective randomized trial of perioperative cefazolin treatment in axillary and groin dissection. AB - One hundred thirty-four patients undergoing axillary or inguinal lymph node dissection were randomized to receive perioperative treatment with either cefazolin or placebo. Risk factors for wound complications (age greater than 60 years, open wound, obesity, smoking, extremity edema, diabetes, arteriosclerotic cardiovascular disease) were recorded. The rate of complications was 36% in 97 patients (72%) with any risk factor present, compared with 14% in patients with no risk factors. Complications were seen in 30% of patients: in 14% after axillary lymph node dissection, and in 64% after inguinal lymph node dissection. The risk of complications was 23% in the group administered antibiotic treatment compared with 36% in that administered placebo treatment. This trend toward fewer complications was seen only after axillary lymph node dissection, when the rate of complications was 8% in the antibiotic-treated group compared with 20% in the placebo-treated group. After inguinal lymph node dissection, the rate of complications was 69% in the antibiotic-treated group compared with 62% in the placebo-treated group. PMID- 1747050 TI - Depletion of dietary arginine inhibits growth of metastatic tumor. AB - The effects of dietary arginine on the growth of a murine colon tumor metastatic to the liver were examined in a model of advanced neoplastic disease. Tumor growth was influenced by arginine both in vivo and in vitro. An arginine supplemented diet stimulated tumor growth by 55% compared with controls. Conversely, an arginine-depleted diet inhibited tumor growth by 78% compared with controls. In vitro culture of both murine and human colon tumor cells confirmed that arginine was necessary for cell growth. Flow-cytometric analysis using propidium iodide and bromodeoxyuridine suggested that colon tumor cells cultured without arginine enter a quiescent S phase and depend on arginine for further growth and cell cycle progression. The potential roles for selective dietary arginine modulation in patients with cancer with advanced disease are discussed. PMID- 1747051 TI - Oncogene-mediated transformation. An in vitro model for colon carcinogenesis. AB - Evaluation of molecular events in human colon polyps and tumors has revealed constitutive elevated expression of c-myc, activation of both ras and src proto oncogenes, and allelic deletion events involving inactivation of putative regulatory genes, including p53. To evaluate the contribution of each of these events to colon carcinogenesis, it is desirable to establish epithelial cell lines representing different stages of neoplastic progression. Such in vitro models can be used to establish a primary role for different genes implicated in neoplastic transformation, identifying events involved in multistep carcinogenesis and delineating the factors modulating cellular transformation. We present herein a summary of such an in vitro model for colon carcinogenesis using the introduction of relevant genetic elements into normal mucosa to identify the molecular steps and accompanying cellular events underlying neoplastic progression in the colon. PMID- 1747052 TI - Treatment of abdominal malignant neoplasms using regional chemotherapy with hemofiltration. AB - The regional delivery of high-dose chemotherapy for malignant neoplasms of the limb with the isolated regional perfusion technique was first described in the late 1950s. Recently, the use of concomitant hemofiltration for rapid systemic drug removal permits the use of higher regional drug levels in treating patients with advanced abdominal malignant neoplasms without complete vascular isolation. Twenty-five patients successfully underwent 42 treatments of high-dose intra arterial chemotherapy with concomitant hemofiltration at Tulane University Medical Center Hospital, New Orleans, La, from 1989 through 1990. One patient (4%) achieved a complete response. Two patients (8%) had partial responses following high-dose intra-arterial chemotherapy with concomitant hemofiltration and their residual disease was resected for cure. Seven patients (28%) achieved a partial response, 11 (44%) had stable disease, and four (16%) had progression of disease. PMID- 1747053 TI - Intraoperative gamma detection probe with presurgical antibody imaging in colon cancer. AB - In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake. PMID- 1747054 TI - Surgical oncology--a specialty or just special? James Ewing Lecture. PMID- 1747055 TI - Paranasal sinusitis in burn patients following nasotracheal intubation. AB - Paranasal sinusitis is a complication of nasotracheal intubation. Of 99 nasally intubated adult patients who survived 48 hours after being burned, 22 who were intubated for more than 7 days underwent a computed tomographic scan of all paranasal sinuses, with timing dictated by the patient's clinical condition. Eight patients had computed tomographic and clinical findings consistent with sinusitis. Treatment consisted of removal of all nasal tubes, oral and topical nasal decongestants, and, when appropriate, culture-specific antibiotics. A subgroup of patients with preexisting sinus disease made up 50% of the patients with sinusitis; early conversion to an oral airway or a tracheostomy should be considered in such patients. Only one patient required surgical drainage of the sinuses. The frequency and morbidity of sinusitis in nasotracheally intubated burn patients does not justify the risk of routine conversion to an oral airway. PMID- 1747056 TI - Gastric emptying after fundoplication with and without proximal gastric vagotomy. AB - Fifty-four patients having antireflux surgery (20 fundoplication alone [group 1] and 34 fundoplication with proximal gastric vagotomy [group 2], had their gastric emptying assessed preoperatively and postoperatively. At 3 years after operation, in group 1, the emptying of a solid meal was significantly accelerated. In contrast, no such acceleration in solid emptying was observed in group 2. Liquid emptying was significantly accelerated in both groups of patients postoperatively. No consistent relationship was found between symptomatic outcome and gastric emptying in either group of patients. We conclude that proximal vagotomy interferes with reflex pathways that are involved in the acceleration of solid gastric emptying after fundoplication. PMID- 1747057 TI - The effect of the Angelchik prosthesis on esophageal and gastric function. AB - The effects of the Angelchik prosthesis on esophageal and gastric function were investigated in 17 patients (11 men and six women; median age, 57 years; age range, 36 to 88 years) who underwent surgery for treatment of gastroesophageal reflux disease. All patients demonstrated unequivocal reflux, either at endoscopy or 24-hour pH testing. There was a significant increase in lower esophageal sphincter pressure after surgery, and no patient demonstrated abnormal reflux on pH testing. Gastric emptying of liquids and solids was not altered by surgery. Six months after surgery, all symptoms except dysphagia had significantly improved. Thirty-three months after surgery, six patients described symptoms as severe as or worse than those before surgery. Four patients had the prosthesis removed, two because of dysphagia alone, one because of reflux and dysphagia, and one because of flatulence and bloating. The patients who required removal of the prosthesis because of dysphagia had gross delay of esophageal emptying. We conclude that the Angelchik prosthesis is an effective antireflux device, but it interferes with esophageal function in some patients, requiring removal of the prosthesis. We think the rate of removal of the prosthesis is too high for its routine use in the treatment of gastroesophageal reflux disease. PMID- 1747058 TI - Trauma experience of a rural hospital. AB - We sought to evaluate the ability of a small rural hospital with level 2 trauma capability to provide adequate care to the patient with multiple trauma. Using the TRISS method, we reviewed 163 patients with trauma admitted to our institution over 2 years. An outcome equivalent to those level 1 centers that contributed to the Major Trauma Outcome Study is documented. The clinical commitment and institutional resources necessary are discussed. PMID- 1747060 TI - Identification and quantitative determination of a carboxylic and a mercapturic acid metabolite of etridiazole in urine of rat and man. Potential tools for biological monitoring. AB - Etridiazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S (5-ethoxy-1,2,4-thiadiazol-3-yl-methyl)-L-cysteine (ET-MA). Selective and sensitive analytical procedures to determine etridiazole, the carboxylic acid ET CA and the mercapturic acid ET-MA in urine were developed. The detection limit of etridiazole, applying GC with nitrogen selective detection (GC-NPD), was 36 micrograms/l urine (CV = 15.4%, n = 3). The detection limit of ET-CA, applying GC with sulphur selective detection (GC-FPD), was 100 micrograms/l urine (CV = 9.8%, n = 3). In urine of rats orally treated with etridiazole, ET-CA and ET-MA were identified as metabolites of etridiazole, whereas in urine of humans given oral etridiazole, only ET-CA was identified. Unmetabolized etridiazole was excreted for less than 0.1% of the administered dose in rats. ET-CA, however, accounted for 22 +/- 9% of the administered dose of etridiazole in rats and for 13 +/- 6% in humans. ET-MA appeared to be a minor urinary metabolite of etridiazole. ET-CA is proposed as a possible biomarker for the biological monitoring of etridiazole. PMID- 1747059 TI - AIDS, drugs of abuse and the immune system: a complex immunotoxicological network. AB - Two of the most interesting questions often asked about AIDS is why many people do not become immunodeficient or get complicating disease when first infected with Human Immunodeficiency Virus (HIV) and what are the "risk factors" making some individuals more susceptible to the disease. A large majority of people with AIDS have a well established history of drug and alcohol abuse. Both drugs of abuse and alcohol have immunotoxic properties as evidenced by a number of studies. These include marked changes in the cellular, humoral and other components of the immune defense mechanism. Such a compromise of the immune system can render it susceptible to the development of AIDS after HIV infection. This paper reviews the evidence suggesting possible links between substance abuse and its immunotoxicology, and their possible roles in the pathogenesis of AIDS. PMID- 1747061 TI - DNA binding, adduct characterisation and metabolic activation of aflatoxin B1 catalysed by isolated rat liver parenchymal, Kupffer and endothelial cells. AB - In vitro studies with rat liver parenchymal, Kupffer and endothelial cells isolated from male Sprague-Dawley rats were undertaken to investigate cell specific bioactivation of aflatoxin B1, DNA binding and adduct formation. In the mutagenicity studies, using homogenates of all three separated liver cell populations (co-incubated with NADP+ and glucose-6-phosphate as cofactors for the cytochrome P-450 monooxygenase system) parenchymal, Kupffer and endothelial cells were able to activate aflatoxin B1 to a metabolite mutagenic to Salmonella typhimurium TA 98. In the case of nonparenchymal cells (i.e. Kupffer and endothelial cells) 10-fold higher concentrations of aflatoxin B1 had to be used to obtain a similar number of revertants to that observed with parenchymal cells. Induction studies with Aroclor 1254 led to a striking decrease in the activation of aflatoxin B1 in parenchymal cells, whereas nonparenchymal cells had a slightly enhanced metabolic activation capacity for aflatoxin B1. Metabolism studies with microsomes from induced and noninduced cells using testosterone as substrate revealed comparable results: after induction with Aroclor 1254, parenchymal cells showed a 60% decrease in the formation rate of 2 alpha-hydroxytestosterone, whereas the formation rate of this metabolite remained unchanged in nonparenchymal cells; 2 alpha-hydroxytestosterone is specifically formed by cytochrome P-450 IIC11, which also catalyses the activation of aflatoxin B1 to its epoxide. When freshly isolated, intact cells were incubated with tritiated aflatoxin B1, a dose-dependent aflatoxin B1 binding to DNA in parenchymal and nonparenchymal cells was observed. HPLC analysis of DNA acid hydrolysates of all three cell types showed the major adduct to be 8,9-dihydro-8-(N7-guanyl)-9 hydroxy-aflatoxin B1. PMID- 1747062 TI - Suppression of sodium arsenite-potentiated cytotoxicity of ultraviolet light by cycloheximide in Chinese hamster ovary cells. AB - Post-treatment with sodium arsenite synergistically increased the cytotoxicity of ultraviolet (UV) light. The potentiation of UV cytotoxicity by sodium arsenite was apparently suppressed by cycloheximide (CHM), a protein synthesis inhibitor. The protective effect of CHM against sodium arsenite-potentiated UV cytotoxicity was well correlated to its activity in inhibiting the synthesis of stress proteins, particularly a small polypeptide with a molecular weight of 8500 dalton. This small stress protein was demonstrated as ubiquitin by immunoprecipitation. Our results also showed that neither ubiquitin induction nor potentiation of UV cytotoxicity by post-treatment with sodium arsenite was observed in the stationary cells. Thus, we suggested that ubiquitin is possibly involved in the action of arsenite in potentiating UV-induced cell killing. PMID- 1747063 TI - Bioavailability of bismuth from 205Bi-labelled pharmaceutical oral Bi preparations in rats. AB - The bioavailability of 205Bi from various 205Bi-labelled pharmaceutical oral bismuth preparations was studied in rats. The intestinal absorption, calculated from 205Bi whole body retention and accumulated 205Bi urinary excretion, was small in general, but significantly higher (0.26-0.33% of dose) from oral bismuth citrates (basic bismuth citrate, colloidal bismuth subcitrate) as compared to basic bismuth nitrate, salicylate, gallate, and bismuth aluminate (0.04-0.11% of dose). After oral administration, the retained bismuth was mainly accumulated in the kidney, followed by bone, red blood cells and the lung. The whole body retention, faecal and urinary excretions of 205Bi were described by a three compartment model. Biological 205Bi half-lives of 10, 36 and 295 h were derived in rats. PMID- 1747064 TI - Corneal edema induced by bis (tributyltin) oxide. AB - Corneal edema induced by bis (tributyltin) oxide (TBTO) was studied with an electron microscope and the accumulation sites of tin were determined with an X ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg TBTO. After time intervals of 2, 4, 6, 8, 10, 12 h after injection, corneas were isolated and provided for electron microscopy. Corneas from untreated rats served as controls. Marked swelling of mitochondria in the corneal endothelial cells occurred at 4 h after TBTO injection. The corneal edema appeared in the endothelial layer and the stroma at 6 h after injection. By X-ray microanalysis, Sn peaks were obtained from swollen mitochondria in the endothelial cells. At 12 h after TBTO injection, edematous swelling of the corneal tissue became more advanced. These results indicated that parenterally administered TBTO accumulated in the mitochondria of corneal endothelial cells. The direct toxic effects of TBTO on the mitochondria might cause the interference with active pump function of endothelial cells and induced the corneal edema. PMID- 1747065 TI - Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 3. No immunosuppressive effect of 2,3,7,8-TCDD in the popliteal lymph node assay (PLNA) in rats. AB - We used a modified version of the popliteal lymph node assay in rats to investigate the immunosuppressive potential of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD). In 10 months we conducted 3 experimental series. Animals were treated with single s.c. injections of TCDD and 7 days later human red blood cells (HRBC) were injected s.c. into the right hind footpad of the rat. Another 7 days later, both popliteal lymph nodes were prepared, weighed, the cell number was counted and the quotients ("index") of these variables from the treated and the untreated side were determined. The doses applied in three experimental series were 600', 60, 6, 0.6, and 0.06 ng TCDD/kg body wt. In the first experimental series only the three highest doses were tested, in a second experimental series doses of 60, 6, 0.6, 0.006 ng TCDD/kg body wt were applied. Combining the results of these two experimental series, a statistically significant difference was found in the cell number index between the controls and the two highest doses tested (60 and 600 ng/kg body wt; p less than 0.01). This result was recently published as an abstract (Korte et al. 1990). However, with slight methodological changes in the third series of experiments (doses applied: 600, 60, 6, 0.6, and 0.06 ng TCDD/kg body wt) and using a greater number of animals we could not confirm these preliminary results. No difference was seen in the immune response to the antigen challenge in controls and in any of the treatment groups. We conclude that TCDD does not clearly influence the immune response as observed in the popliteal lymph node assay under our experimental conditions. PMID- 1747066 TI - Distribution and effects on cytochrome P450 system of two hexachlorobiphenyl isomers in the rat. AB - Tissue distribution and effects induced by 2,2',4,4',5,5'-hexachlorobiphenyl (245 HCB) on cytocrome P450 isozymes were compared with those of 2,2',3,3',6,6' hexacholorobiphenyl (236-HCB). Male Wistar rats were given a single intragastric dose (23 mg/kg body wt) of either isomer, and killed after 72 h. At termination the tissue concentrations of 245-HCB were considerably higher than those of 236 HCB, suggesting a more effective metabolism of the latter. The binding affinity of 236-HCB to cytochrome P450 was higher and the magnitude of binding greater than of 245-HCB. 245-HCB-treatment elevated the hepatic concentration of cytochrome P450 and also the activities of 7-pentoxyresorufin O-depentylase (50 fold), aniline p-hydroxylase (2-fold) and 7-ethoxycoumarin O-deethylase (2-fold), a response typical of phenobarbital-type inducers. In the Western immunoblot of liver microsomes from 245-HCB treated rats, an increased amount of P450IIB 1/2 was detected by a monoclonal antibody 2-66-3, which specifically detects phenobarbital inducible isoenzymes. The minimum molecular mass of the P450 isozyme induced was 52 kDa. After 236-HCB administration, a weak inducing effect was observed. PMID- 1747067 TI - Protective effect of O-phenanthroline against mechlorethamine toxicity in the rat liver slice system and in the guinea pig skin. AB - The effect of O-phenanthroline (OP) on mechlorethamine hydrochloride (HN2) toxicity was studied in in vitro and in vivo experiments. Incubation of HN2 with the in vitro rat liver slice system resulted in leakage of alanine aminotransferase (ALT) in a time-dependent manner. Exposure of the slices to HN2 for 4 h caused 79.2% ALT leakage. In the presence of OP enzyme leakage was reduced to 28.7%. OP-induced protection was shown to be dose dependent. Other metal chelators such as dithiothreitol (DTT) and EDTA (ethylenediaminetetraacetic acid) had a weak effect on HN2 cytotoxicity. The protective activity of OP was also demonstrated in in vivo skin toxicity studies in the guinea pig. The ulcerative effect of topically applied HN2 was inhibited by OP even when applied 10 min following the alkylator. Histology of NH2-treated skin showed epidermal ulceration associated with a covering layer of encrusted exudate. However, only a slight diffuse acanthosis of the epidermal layer was observed when OP was applied for 10 min after the vesicant. It is suggested that OP may be used for the prevention of tissue damage caused by antineoplastic treatment with nitrogen mustard. It might also be employed in military medicine as an antidote to the chemical weapon sulfur mustard. PMID- 1747068 TI - Respiratory effects of trimellitic anhydride aerosols in mice. AB - Groups of mice were exposed to trimellitic anhydride (TMA) aerosols for 30 min at concentrations ranging from approximately 2 to 150 mg/m3. The sensory and pulmonary irritating properties of TMA were assessed during these exposures. Sensory irritation, as evidenced by a lenghthening of the time of expiration (TE), was not evoked in any exposure. However, TMA aerosols evoked other rapid, reversible alterations of respiratory cycle timing, suggestive of pulmonary irritation. The time of inspiration (TI) and expiration (TE) decreased as TMA exposure concentration was increased. Also, characteristic pauses (i.e., apneic periods) occurred between breaths. The length of these pauses (TP) increased as TMA exposure concentration was raised. Respiratory frequency (f) was dependent upon the magnitude of increase in TP. At lower TMA concentrations, TP was short and f was elevated, whereas at higher concentrations, TP was long and f was reduced. Interestingly, there was no other evidence of pulmonary irritation besides the alterations in respiratory cycle timing. Histopathological evaluation of the respiratory tracts of TMA-exposed animals revealed no changes from those of controls. Finally, there was no evidence of cumulative or delayed pulmonary effects in mice repeatedly exposed to TMA aerosols. These acute changes in respiratory cycle timing may have occurred as a result of stimulation of vagal nerve endings along the conducting airways and in the deep lung, directly produced by TMA aerosols. PMID- 1747069 TI - Chronic intoxication with acetaldehyde stimulates collagen biosynthesis in rat liver. AB - It was found that chronic intoxication of rats with acetaldehyde results in a distinct, progressive increase of 5(3)H-proline incorporation into collagen synthesized by liver. At the same time, biosynthesis of other proline-containing (noncollagenous) proteins does not change significantly. The effects are similar to those induced by chronic intoxication of rats with ethanol. Since acetaldehyde is an intermediary metabolite formed during ethanol oxidation in liver, it may be concluded that acetaldehyde is a factor responsible for alcohol-induced liver fibrosis. PMID- 1747070 TI - Potential tolerance against bromobenzene-induced acute hepatotoxicity due to prior subchronic exposure. AB - Groups of adult male Sprague-Dawley rats were treated i.p. with 0, 0.3 and 0.5 mmole bromobenzene (BB)/kg per day in corn oil, 5 days a week for 4 weeks. Thereafter, one half of each of these groups was treated i.p. with a single acute toxic dose of 2.5 mmole BB/kg. Urines were then collected for 24 h and the animals were then sacrificed. The hepatotoxicity induced by an acute dose of BB was significantly reduced due to prior subchronic exposure to BB at 0.5 mmol/kg, but not so at 0.3 mmol/kg. These data indicate a potential tolerance against acute hepatotoxicity of BB due to prior subchronic exposure. A significant increase in the urinary excretion of thioethers or mercapturic acids of BB combined with a significant increase in the urinary level of p-bromocatechol due to prior subchronic treatment with 0.5 mmol BB/kg relative to those due to acute treatment alone was observed. Thus enhanced bromobenzene metabolism could partly explain such potential tolerance against its acute hepatotoxicity. Such protection may also be related to certain cellular events which might occur subsequent to metabolic activation of BB. PMID- 1747071 TI - Gastrointestinal absorption of Cd-metallothionein and cadmium chloride in mice. AB - CdCl2 or Cd-metallothionein (MT) (6 micrograms Cd with 2.25 muCi (83.25 KBq) 109Cd) was given orally to mice, which were sacrificed at 30 min and 2 h after intubation. Although 109Cd in Cd-MT was excreted rapidly into the urine, its absorption was found to be significantly less than that of CdCl2. The poor absorption was due to a decrease of Cd-MT uptake into the intestine. Cadmium chloride taken up into the mucosa could stimulate MT synthesis even 30 min after its intubation. However, the percentage of MT-bound Cd in the Cd of intestinal supernatants was lower with CdCl2 (62% at 30 min and 2 h) than with Cd-MT (78% and 84% at 30 min and 2 h, respectively). These results suggest that the transport mode of lumenal Cd-MT to mucosal cells is different from that of lumenal CdCl2. Lumenal Cd-MT is probably internalized into intestinal cells in an intact form. Furthermore, the Cd-MT may pass through the basolateral membrane in this form. This hypothesis was supported by the different distributions of Cd in the liver and kidney after Cd-MT and CdCl2 intubations. PMID- 1747072 TI - Crevicular IgG antibodies and Streptococcus mutans on erupting human first permanent molars. AB - The specific IgG antibody activity against indigenous Streptococcus mutans in gingival crevicular fluid (GCF) was determined in 25, 6-7-yr-old children. Samples of plaque and GCF were collected from all erupting first permanent molars. Plaque samples were also collected from the adjacent second primary molars. The presence of clinical caries was scored as defs. In the same individual a highly significant correlation (p less than 0.005) was found between the level of specific antibody activity in GCF when comparing first permanent molars with each other. No correlation was found between the specific antibody activity in GCF and the number of indigenous Strep. mutans colonizing the buccal surfaces of the first permanent molars. Caries-free children had significantly less specific antibody activity in GCF than children with caries experience (p less than 0.05). In the same child a highly significant correlation (p less than 0.0001) was found between the level of colonization by mutans streptococci on the permanent molars and the adjacent second primary molars. PMID- 1747073 TI - Subcellular co-localization and co-variations of two vitamin D-dependent proteins in rat ameloblasts. AB - The immunocytochemical patterns of calbindin-D9k (CaBP 9k) and calbindin-D28k (CaBP 28k) were compared by light and electron microscopy throughout amelogenesis. Labelling on serial sections and co-localization of CaBPs confirmed that the two proteins were restricted to a single cell type, the ameloblasts. Their quantity increased during presecretion, was stable during secretion and alternately high and low during the cyclic modulation of ameloblasts which occurs during maturation. Ruffle-ended ameloblasts contained the highest apparent concentration. Investigations with several fixatives indicated that the CaBPs were present in the cytosol and the nucleus, although there were slight differences with various fixatives by light microscopy. Their concentrations in these compartments varied in parallel throughout amelogenesis. However, mitochondria contained only immunoreactive CaBP 9k. While the distribution of CaBP 9k in zones containing Golgi apparatus and rough endoplasmic reticulum was similar, CaBP 28k concentration has, in another paper, been shown to be higher near the rough endoplasmic reticulum. PMID- 1747074 TI - Morphological and immunocytochemical characterization of cultured rat incisor cervical epithelial cells. AB - Epithelial cells from the cervical loop of the rat incisor were isolated by co culture of apical explants with growth-arrested 3T3 fibroblasts. The epithelial phenotype of the expanding outgrowths was confirmed 10 days after the seeding of the explants by phase-contrast microscopy and immunocytochemical identification of cytokeratins. After 3 weeks in culture, the epithelial cells covered the entire surface of the coverslips and were then passaged. Subcultures gave rise to a confluent sheet within 10-12 days. Light and electron microscopy showed that confluent cervical epithelial cells generally reconstituted a bi-layered structure similar to Hertwig's epithelial sheath. Epithelial cells from the rat palate, cultured and subcultured according to the same procedure, organized themselves in 5-6 cell layers, the upper cells having generally a squamous morphology. Synthesis of extracellular matrix molecules by rat incisor cervical epithelial cells was studied with specific antibodies. These cells failed to produce type I collagen, but synthesized all the major basement membrane components (type IV collagen, laminin, heparan sulphate proteoglycan and fibronectin). These observations suggest that the culture conditions allowed the reconstitution of a typical Hertwig's epithelial sheath by rat incisor cervical epithelial cells. PMID- 1747075 TI - Degradation of collagen types I, III, IV and V by extracellular proteinases of an oral flagellate Trichomonas tenax. AB - Proteinases secreted by an axenic strain of Trichomonas tenax were active against native types I, III, IV and V collagens when evaluated by polyacrylamide gel electrophoresis. Degradation of all four collagen types was temperature dependent. Basement membrane type IV collagen was digested most effectively. An inhibition of all collagenolytic activities by a specific inhibitor of cysteine proteinases, E-64, and activation by a reducing agent, dithiothreitol, indicated the involvement of cysteine proteinases of the oral flagellate in the cleavage of collagen. PMID- 1747076 TI - A histochemical study on the distribution of melanin in human oral epithelium at six regional sites. AB - Oral mucosa from six sites in 95 autopsies was tested for melanin using the Masson-Fontana silver reduction method. Melanin was detected in 51.6% of labial, 46.3% of palatal, 45.3% of buccal, 28.4% of mandibular gingival, 25.3% of lingual and 21.1% of maxillary gingival samples. 93.7% of epidermal samples from the same population were positive. In 24.2% of the subjects there was no detectable melanin at any intraoral site and 4.2% showed activity in all six sites. The mean number of positive oral sites per individual was 2.2. There are thus regional differences in oral epithelial melanocyte activity, but no parallel with the known regional incidence of primary oral melanoma. PMID- 1747077 TI - The extent and distribution of intratubular collagen fibrils in human dentine. AB - Dentine of 27 permanent human teeth was examined by scanning electron microscopy. The teeth were incisors, canines, premolars and molars, ranging in age from 18 to 54 yr. Intratubular collagen was found in 65% of the dental tubules in inner dentine (closest to the pulp) with 16% of the tubules containing large collagen bundles occupying more than one-fifth of the lumen. In middle dentine the corresponding figures were 42 and 7%, and for outer dentine, 12 and 0% This pattern of distribution was the same for all tooth families examined and appeared to be unrelated to age. PMID- 1747078 TI - An instrument to monitor physiological and environmental parameters associated with heat stress on an ambulatory subject. AB - This paper outlines the development and construction of an instrument for use on an ambulatory subject which monitors selected physiological and environmental parameters that are a reflection of the degree of physiological strain associated with heat stress. The resulting instrument is rugged, reliable, and uses existing practical technology for in-the-field ambulatory monitoring, and provides minimal restriction to subject movement. The physiological parameters monitored (heart rate and skin temperature) were selected following examination of systemic, skin, and psychoneurotic heat disorders, with the environmental parameters (wind velocity, ambient temperature and relative humidity) based on existing heat stress indices' correlation with physiological parameters. A microprocessor is utilized for data acquisition, mathematical computation and long term storage, and software for downloading the data to a large mainframe computer is provided. Following calibration of the transduction circuits, the instrument was assembled and tested. Improvements are required to obtain the reliability originally envisaged. Additional field trials would see the collection of data to establish criteria to determine the values of the parameters monitored enabling prediction of the onset of heat stress in hot, humid environments. PMID- 1747079 TI - Distribution of expired air in carry cots--a possible explanation for some sudden infant deaths. AB - A possible explanation for the cause of some cot deaths is examined by placing an appropriate cot death model on a cold wet sheet so that its "breath" is directed downwards across the sheet, thereby being cooled and becoming heavy enough to stay trapped in the hollow of the mattress. The breath is then available for rebreathing by the model. The level of carbon dioxide (CO2) "inhaled" is showed to be lower in nostril breathers, singletons and in bassinets and higher with mouth breathing models, in "twins", and in carry cots, especially if the model's head is accidentally covered. Under these conditions a living infant would become progressively acidotic due to inability to adequately excrete its metabolic CO2. This must inevitably be accompanied by increasing hypoxia. If left undisturbed in this predicament, it would rebreathe its own breath for the period of time between feeds and develop increasing degrees of asphyxia, depending on the circumstances outlined. PMID- 1747081 TI - College membership standards. PMID- 1747080 TI - Management and autopsy of a radioactive cadaver. AB - A 69 year old male was treated with an ablative dose of 3.7 GBq (100 mCi) of I131 for carcinoma of the thyroid and died 10 days after administration. The requirement for an autopsy and the level of radiation still present in the body necessitated the intervention of Radiation Safety Personnel to minimise support staff radiation exposure and area contamination. Preventative measures were taken in accordance with the ALARA principle and a detailed procedure is presented as a suggested model for any future occurrence. PMID- 1747082 TI - Recent developments in time-dose modelling. AB - Two recent innovations in time-dose models are reviewed: the linear-quadratic (L Q) and the variable-exponent Time-Dose Factor (TDF) models. The basic L-Q equations for fractionated and continuous (brachytherapy) regimes are presented as well as those for incomplete repair and short half life radionuclides. None of these equations has provision for a repopulation factor, so a "wasted ERD" parameter is introduced, which is a linear function of overall treatment time, with incorporation of a lag time if desired. For low dose rate therapy, an effective treatment time is defined, at which the ERD reaches its maximum value when the rate of increase due to irradiation equals the rate of decrease due to repopulation. The variable-exponent TDF model has a volume-effect parameter and scaling factors which make TDFs of 100 correspond to tolerance for all volumes of tissue treated, for both fractionated and continuous therapy. These, as well as the exponents, are all tissue-specific. Volume-effect and scaling factors are also appropriate for the L-Q equations. With these it is possible to apply the TDF and L-Q models to problems which involve inhomogeneous dose distributions. Several examples of the use of these models are presented. PMID- 1747083 TI - A mathematical study of non-Newtonian blood flow through elastic arteries. AB - Existing models of blood flow through arteries are revisited. Non-Newtonian and viscous properties are also considered. Treating blood as a non-Newtonian, pseudoplastic fluid obeying the power law, the flow equations are rigorously derived, using the same principles applied in existing models. An appropriate and more physically and physiologically correct model is obtained. Another model in exponential form is also derived. The resulting equations are solved numerically for a range of parameters and the various graphs are compared. PMID- 1747084 TI - Optical design in a flow system for imaging cells. AB - The imaging flow cytometer is an instrument that acquires the images of cells in a flow system. These images are analyzed for real-time cell classification and sorting. The optical units in the system perform the functions of laser beam focusing, cell detection, and cell imaging. The glass nozzle in which the cell stream flows introduces air-glass optical interfaces, resulting in optical aberrations that impair performance. This report describes the analysis of the optical aberrations in nozzles fabricated from a cylindrical glass capillary tube. Flat surfaces could be machined on the originally cylindrical surface to reduce the severity of these aberrations. The analysis shows that a nozzle with three flat surfaces is a feasible low-cost solution. PMID- 1747085 TI - The temperature for fusing blood vessels using a copper vapour laser. AB - Specimens of canine femoral or carotid artery were preserved at the temperature of liquid nitrogen and restored to room temperature before use. Fusing experiments were performed by repeatedly scanning along cuts of 1.0 cm long using a copper vapour laser at a power level of 500 mW. The laser was delivered via a 0.2 mm diameter optical fibre, 10 cm from the specimen, providing a beam spot area of 0.125 mm2 (a power density of 400 W cm-2). Drops of saline solution were applied to the irradiated areas for cooling at a rate of one drop every five seconds. At a scanning rate of 1 cm s-1, about 300 s were taken to successfully fuse a cut of 1 cm long with minimum tissue damage. Direct measurement of tissue temperatures whilst the beam was applied was not possible because of the interference of the laser, therefore the fusing temperature was estimated by the method of extrapolation. Time dependence of the surface temperature at the centre of the target area immediately after exposure and the spatial distribution of the surface temperature around the target area during exposures were measured using a thermocouple thermometer. The fusing temperature was estimated to be 62 degrees C by extrapolation of the time dependence and spatial distributions. PMID- 1747086 TI - Computer generation of random deviates. AB - The need for random deviates arises in many scientific applications, such as the simulation of physical processes, numerical evaluation of complex mathematical formulae and the modeling of decision processes. In medical physics, Monte Carlo simulations have been used in radiology, radiation therapy and nuclear medicine. Specific instances include the modelling of x-ray scattering processes and the addition of random noise to images or curves in order to assess the effects of various processing procedures. Reliable sources of random deviates with statistical properties indistinguishable from true random deviates are a fundamental necessity for such tasks. This paper provides a review of computer algorithms which can be used to generate uniform random deviates and other distributions of interest to medical physicists, along with a few caveats relating to various problems and pitfalls which can occur. Source code listings for the generators discussed (in FORTRAN, Turbo-PASCAL and Data General ASSEMBLER) are available on request from the authors. PMID- 1747087 TI - Mammography in New Zealand: radiation dose and image quality. AB - The mean glandular doses to the breast, image quality and machine performance have been determined for all mammographic x-ray facilities in New Zealand, during 1988-89. For 30 mm and 45 mm phantoms the mean doses per film were 1.03 +/- 0.56 mGy and 1.97 +/- 1.06 mGy. These doses are within international guide-lines. Image quality (detection of simulated microcalcifications, and contrast-detail performance) was found to depend on focal spot size/FFD combination, breast thickness, and film processing. The best machines could resolve 0.2 mm aluminium oxide specks with the contact technique. The use of a grid improved image quality as did magnification. Extended cycle film processing reduced doses, but the claimed improvement in image quality was not apparent from our data. The machine calibration parameters kVp, HVL and timer accuracy were in general within accepted tolerances. Automatic exposure controls in some cases gave poor control of film density with changing breast thickness. PMID- 1747088 TI - Environmental events and psychopathology. Restoring the balance. PMID- 1747089 TI - The effects of divorce on children's adjustment. Review and implications. AB - Divorce has become one of the most frequent environmental stressors experienced by children. This article reviews present conceptualizations of children's adaptation to divorce. Most notably, researchers have moved away from the view that family structural variables, such as single-parent status, necessitate the development of psychopathology in children. In recent years, investigators have shifted their attention to events that accompany marital dissolution, rather than the event of divorce per se. Such process variables have been identified as more salient correlates of children's adjustment. Additionally, the article examines children's short- and long-term adjustment to divorce, specific problem areas that are common among children from divorced families, and directions for future investigations. PMID- 1747090 TI - Depression in pediatric illness. AB - Depression is a major complication of medical illness in adults and is increasingly being recognized as a complication of pediatric illness. The author reviews issues in the assessment and diagnosis of depression in pediatric illness and reviews recent studies on the prevalence of and risk factors for depression in different illnesses. Pediatric illness may be a major stressor that precipitates depression in children vulnerable because of life events, family dysfunction, or predisposition to affective illness. PMID- 1747091 TI - Effects of unemployment on mental health in the contemporary family. AB - This article summarizes research conducted in the past 20 years concerning mental health effects of involuntary job loss. The majority of studies and previous reviews focus on unemployment effects on men. Although these studies are also reviewed, this article highlights studies of (a) the involuntarily unemployed woman, (b) the spouse of the unemployed person, and (c) their children. Within each of these research areas, the authors consider studies grouped according to their methodological strength for drawing causal inferences about the impact of job loss on psychological status, ranging from cross-sectional to longitudinal to prospective studies. The implications of the unemployment literature not only for future research but also for clinical practice are addressed. Knowledge of family effects of this stressful life circumstance is critical to developing effective treatment plans for patients who, although perhaps not the direct victims of job loss themselves, may nevertheless present with problems indirectly caused or exacerbated by unemployment within the family. PMID- 1747092 TI - Homicide as a risk factor for PTSD among surviving family members. AB - In this National Institute of Justice-funded study, random digit dialing telephone survey methodology was used to screen a large, nationally representative sample (N = 12,500) of the noninstitutionalized U.S. adult population to identify surviving family members and friends of victims of criminal homicide and alcohol-related vehicular homicide. A total of 9.3% of the national sample had lost a family member or friend to homicide. Immediate family survivors (n = 206) completed an interview assessing demographic characteristics and DSM-III-R criteria for homicide-related post-traumatic stress disorder (PTSD). The interview participation rate was 84%. Among immediate family survivors, 23.3% developed PTSD at some point in their lifetimes, and 4.8% met full diagnostic criteria for PTSD during the preceding 6 months. Survivors of criminal and vehicular homicide victims were equally likely to develop PTSD. Survivors who experienced the homicide during their childhood, adolescence, or adulthood also showed equal likelihood of PTSD. Clinical implications of findings are discussed. PMID- 1747093 TI - Child, adolescent, and adult victims of residential fire. Psychosocial consequences. AB - Behavior of children, adolescents, and adults during and after a residential fire was objectively assessed. Antecedents, behaviors, and consequences of the nighttime residential fire immediately and 1 month following the fire were obtained. Also, the extent of agreement between children/adolescent and adult functioning was determined. Eight children and adolescents and 12 adults were individually interviewed. Results showed that individuals' reactions to residential fire could be assessed, and several PTSD-related symptoms were expressed. A follow-up study in which 25 adolescent boys whose dormitory had been totally destroyed by fire were compared to 13 boys who had not experienced the fire showed similar findings. These findings add to the dearth of literature concerning children and adolescents in fire-related disasters. PMID- 1747094 TI - Molecular identification and comparison of the starch synthase bound to starch granules between endosperm and leaf blades in rice plants. AB - Normal (nonglutinous) rice plants (Oryza sativa and O. glaberrima) contain more than 18% amylose in endosperm starch, while waxy (glutinous) plants lack it in this starch. In contrast, leaf starch contained more than 3.6% amylose even in waxy plants. SDS-PAGE analysis of proteins bound to endosperm starch granules in the normal plants revealed a single band with a Mr of 60 kd, whereas waxy plants did not exhibit a similar band. The activity of starch synthase (NDP-glucose starch glucosyltransferase) was completely inhibited by antibody against the 60 kd protein. Thus, we conclude that the 60-kd protein is the waxy protein encoded by the Wx allele, which also plays a role in the synthesis of nonglutinous starch in endosperm tissue. In leaf blades, the proteins bound to starch granules separated into five bands with Mr's of 53.6 to 64.9 kd on SDS-PAGE. Analysis of these proteins by immunoblotting using antiserum against Wx protein and inhibition of starch synthase activity by the synthase antibody revealed that none of these proteins was homologous to Wx protein. We suggest that the synthesis of amylose in leaf blades is brought about by a protein encoded by a gene(s) different from the Wx gene expressed in the endosperm. PMID- 1747095 TI - Isolation of Caenorhabditis elegans mutants lacking alcohol dehydrogenase activity. AB - Alcohol dehydrogenase (ADH) and the genes encoding this enzyme have been studied intensively in a broad range of organisms. Little, however, has been reported on ADH in the free-living nematode Caenorhabditis elegans. Extracts of wild-type C. elegans contain ADH activity and display a single band of activity on a native polyacrylamide gel. Reaction rate for alcohol oxidation is more rapid with higher molecular weight alcohols as substrate than with ethanol. Primary alcohols are preferred to secondary alcohols. C. elegans is sensitive to allyl alcohol, a compound that has been used to select for ADH-null mutants of several organisms. Allyl alcohol-resistant mutant strains were selected from ethylmethanesulfonate (EMS)-mutagenized nematode populations. ADH activity was measured in extracts from eight of these strains and was found to be low or nondetectable. These results form a basis for molecular and genetic characterization of ADH expression in C. elegans. PMID- 1747096 TI - Genetics and polymorphism of a duplicated malate dehydrogenase (MDH) locus in the grasshopper Oxya japonica japonica (Orthoptera:Acrididae:Oxyinae). AB - A biochemical genetic study of the enzyme malate dehydrogenase (MDH) was conducted in the grasshopper Oxya j. japonica. Analysis of MDH electrophoretic variation in this species of grasshopper shows that one of the two autosomal loci for MDH in grasshoppers, the Mdh-2 locus, controlling the anodal set of MDH isozymes, is duplicated. Results of breeding studies confirm this and the observed polymorphism at the Mdh-2 locus in the two populations of Oxya j. japonica studied can be attributed to three forms of linked alleles at the duplicated locus in equilibrium in both populations. In this respect, all individuals of this species possess heterozygous allelic combinations at the duplicated Mdh-2 locus, which may account for the spread of the duplicated locus in the populations of this species of grasshopper. PMID- 1747097 TI - Conservation genetics of the koala (Phascolarctos cinereus). II. Limited variability in minisatellite DNA sequences. AB - We have examined variability in TaqI and EcoRI restriction fragment sizes of DNA from the koala (Phascolarctos cinereus) using six HVR (hypervariable region) probes which reveal complex, individual-specific restriction patterns in humans and other species. Frequency of band-sharing among unrelated koalas was extremely high. This result is likely to be a consequence of the history of near-extinction and artificial recolonization of the populations we have studied, rather than a general marsupial or koala-wide phenomenon. PMID- 1747098 TI - Biochemical and physiological studies of soluble esterases from Drosophila melanogaster. AB - Twenty-two soluble esterases have been identified in D. melanogaster by combining the techniques of native polyacrylamide gel electrophoresis and isoelectric focusing. The sensitivity of each isozyme to three types of inhibitors (organophosphates, eserine sulfate, and sulfydryl reagents) identified 10 as carboxylesterases, 6 as cholinesterases, and 3 as acetylesterases. Three isozymes could not be classified and no arylesterases were identified. The carboxyl- and cholinesterases could each be further divided into two subclasses on the basis of inhibition by organophosphates and sulfhydryl reagents, respectively. Choline- and acetylesterases have characteristic substrate preferences but both subclasses of carboxylesterases are heterogeneous in substrate utilization. Subclass 2 carboxylesterases exhibit diverse temporal expression patterns, with subclass 1 carboxylesterases generally found in larvae and subclass 1 cholinesterases and acetylesterases more characteristic of pupae and adults. Tissues showing the greatest number of isozymes are larval body wall (eight) and digestive tract (six in larvae, six in adults). Carboxylesterases are distributed across a wide range of tissues, but subclass 1 cholinesterases are generally associated with neural or neurosecretory tissues and subclass 2 cholinesterases with digestive tissues. PMID- 1747099 TI - Genetic differentiation of Drosophila melanogaster populations as assessed by two dimensional electrophoresis. AB - Seven populations of Drosophila melanogaster, representing a worldwide distribution, were compared using two-dimensional protein gel electrophoresis. A total of 611 protein spots was scored, which probably represent a sample of over 500 loci that were surveyed. Of the protein spots scored, 521 spots were found to be invariant, but another 90 spots were found to be variable among the populations. Of these variable protein spots, 12 were found to be present in only one population. All the populations, except one, had at least one protein spot restricted to itself. However, the Japanese population had by far the most, with five protein spots restricted to this one population, which has been observed in previous studies of private alleles in oriental populations. The mean genetic similarity (F) found among the seven populations was 0.965, with a range of between 0.956 and 0.977. This is similar to previous reports of lower variation found in population genetic surveys using two-dimensional electrophoresis. It was found that the historical relationships among these populations was somewhat congruent with the geographic distribution of the populations, but as in previous studies, it was not exactly coincident. PMID- 1747100 TI - Two-dimensional electrophoresis of 1D-encoded B and D glutenin subunits in common wheats with similar omega gliadins. AB - Gli-D1-encoded omega gliadins of bread wheats show little variation; their electrophoretic patterns can be classified into two main groups which broadly resemble the patterns found in the cultivars Chinese Spring and in Cheyenne. B and D subunits of low molecular weight glutenin encoded by the chromosome 1D loci Glu-D3 and Gli-D1, respectively, also showed little variation. D subunits were found only in bread wheats with "Chinese Spring-type" omega gliadins and they all exhibited the same electrophoretic pattern. This material also showed very similar B subunits. "Cheyenne-type" bread wheats displayed the same electrophoretic distribution of chromosome 1D-encoded B subunits, although they were slightly different from that found in Cheyenne itself. PMID- 1747101 TI - Regulation of arachidonic acid release in vascular endothelium. Ca(2+)-dependent and -independent pathways. AB - Ca2+ metabolism and its relationship to arachidonic acid release were studied in cultured pig aortic endothelial cells. When cells were treated with bradykinin, a rapid rise in intracellular Ca2+ concentration ([Ca2+]i) occurred. Arachidonic acid release from cells prelabelled with [3H]arachidonic acid and subjected to flow-through conditions closely followed the changes in [Ca2+]i. Attenuation of the Ca2+ response by chelating extracellular and intracellular Ca2+ or by desensitization of receptors led to comparable attenuation of arachidonate release. Activation of protein kinase C inhibited Ca2+ mobilization in response to bradykinin and stimulated arachidonic acid release. Inhibition of protein kinase C had no effect on bradykinin-stimulated arachidonic acid release, suggesting that protein kinase C does not mediate the bradykinin response. The role of GTP-binding regulatory proteins (G-proteins) in mediating the bradykinin response was also investigated. Bradykinin-stimulated arachidonic acid release was not diminished by preincubation with pertussis toxin. Treatment with the G protein activator AlF4- resulted in the release of a large pool of arachidonic acid and the formation of lysophospholipids. Combined treatment with AlF4- and bradykinin resulted in a greater than additive effect on arachidonic acid release. In contrast with bradykinin, AlF(4-)-stimulated arachidonic acid release was not dependent on the presence of extracellular Ca2+ or the mobilization of intracellular Ca2+. These results demonstrate Ca(2+)-dependent (bradykinin) and Ca(2+)-independent (AlF4-) pathways of phospholipase A2 activation. PMID- 1747102 TI - Polyamine catabolism in rodent and human cells in culture. AB - N1-Acetylspermidine (N1AcSpd) accumulates in late exponential phase, or after certain stresses such as heat shock, in both human tumour (A549) and rodent (HTC, CHO) cells, grown in medium containing an inhibitor of the FAD-dependent polyamine oxidase (PAO). Inhibition of PAO has little effect on cell growth or on the cellular content of the major polyamines, putrescine, spermidine or spermine, found in proliferating cells in culture, but decreases cellular putrescine content in heat shocked cells. Putrescine and spermidine are generated when N1AcSpd or N1-acetylspermine (N1AcSpm) respectively is added to either human or rodent cells depleted of the former amines by alpha-difluoromethylornithine. N1AcSpm is formed in polyamine-depleted human A549 cells when N1AcSpd is added to cultures treated with the PAO inhibitor. This reaction does not occur in either rodent line, suggesting that N1AcSpd can be converted directly into N1AcSpm in human, but not rodent, cells under specific conditions. The data presented demonstrate that a variety of human and rodent cells express PAO activity and catabolize polyamines by a mechanism which includes PAO. PAO activity is of little consequence to proliferating A549, HTC or CHO cells in culture, but does produce new putrescine in both late-exponential-phase and heat-shocked cells. These findings suggest that polyamine catabolism is part of a general response of both rodent and human cells to a variety of environmental and physiological stresses. PMID- 1747103 TI - Determination of the intracellular sites and topology of glucosylceramide synthesis in rat liver. AB - We examined the intracellular site(s) and topology of glucosylceramide (GlcCer) synthesis in subcellular fractions from rat liver, using radioactive and fluorescent ceramide analogues as precursors, and compared these results with those obtained in our recent study of sphingomyelin (SM) synthesis in rat liver [Futerman, Stieger, Hubbard & Pagano (1990) J. Biol. Chem. 265, 8650-8657]. In contrast with SM synthesis, which occurs principally at the cis/medial Golgi apparatus, GlcCer synthesis was more widely distributed, with substantial amounts of synthesis detected in a heavy (cis/medial) Golgi-apparatus subfraction, a light smooth-vesicle fraction that is almost devoid of an endoplasmic-reticulum marker enzyme (glucose-6-phosphatase), and a heavy vesicle fraction. Furthermore, no GlcCer synthesis was detected in an enriched plasma-membrane fraction after accounting for contamination by Golgi-apparatus membranes. These results suggest that a significant amount of GlcCer may be synthesized in a pre- or early Golgi apparatus compartment. Unlike SM synthesis, which occurs at the luminal surface of the Golgi apparatus, GlcCer synthesis appeared to occur at the cytosolic surface of intracellular membranes, since (i) limited proteolytic digestion of intact Golgi-apparatus vesicles almost completely inhibited GlcCer synthesis, and (ii) the extent of UDP-glucose translocation into the Golgi apparatus was insufficient to account for the amount of GlcCer synthesis measured. These findings imply that, after its synthesis, GlcCer must undergo transbilayer movement to the luminal surface to account for the known topology of higher-order glycosphingolipids within the Golgi apparatus and plasma membrane. PMID- 1747105 TI - A low-temperature method for the isolation of small-intestinal epithelium along the crypt-villus axis. AB - A variety of enzymic and non-enzymic methods to isolate epithelium from the small intestine have been previously published. Sequential fractionation of cells from the villus to the crypt has been reported in some of these papers, which allows the comparative study of terminally differentiated and proliferative cell phenotypes. However, these methods often involve the incubation of tissues at 37 degrees C, which may affect the structural and biochemical integrity of the cells. We have developed a rapid low-temperature (4 degrees C) method for isolating purified populations of crypt and villus cells from mouse and rat intestines. The fractionated cells have been partially characterized, and the potential value of the procedure has been indicated by the ability to analyse the comparative protein and mRNA expression along the crypt-villus axis. PMID- 1747104 TI - A classification of glycosyl hydrolases based on amino acid sequence similarities. AB - The amino acid sequences of 301 glycosyl hydrolases and related enzymes have been compared. A total of 291 sequences corresponding to 39 EC entries could be classified into 35 families. Only ten sequences (less than 5% of the sample) could not be assigned to any family. With the sequences available for this analysis, 18 families were found to be monospecific (containing only one EC number) and 17 were found to be polyspecific (containing at least two EC numbers). Implications on the folding characteristics and mechanism of action of these enzymes and on the evolution of carbohydrate metabolism are discussed. With the steady increase in sequence and structural data, it is suggested that the enzyme classification system should perhaps be revised. PMID- 1747106 TI - Fluoroaluminate treatment of rat liver microsomes inhibits GTP-dependent vesicle fusion. AB - 1. Inhibition of GTP-dependent membrane fusion of rat liver microsomes requires preincubation of the membranes with GDP (17 microM) and relatively high Mg2+ concentration (0.5 mM) as well as AlCl3 (30 microM) and KF (5 mM). Preincubation is required for maximal inhibition (75%). 2. Vesicle fusion in rat liver microsomes has been demonstrated in the absence of polyethylene glycol (PEG). Further, inhibition by AlF4- of GTP-dependent vesicle fusion in the absence of PEG has been demonstrated. 3. Under similar preincubation conditions AlF4- can bring about inhibition (80%) of the high-affinity PEG-stimulated GTPase activity in rat liver microsomes, previously described by Nicchitta, Joseph & Williamson [(1986) FEBS Lett. 209, 243-248]. 4. Preincubation of small-Mr GTP-binding proteins (Gn proteins) on nitrocellulose strips with GDP (20 pM), AlCl3 (30 microM) and KF (5 mM) results in inhibition of binding of guanosine 5'-[gamma [35S]thio]triphosphate to Gn proteins. The extent of inhibition of this binding differs for different Gn proteins. PMID- 1747107 TI - Large-scale purification and characterization of the major phosphoproteins and mucins of human submandibular-sublingual saliva. AB - The major components of human submandibular-sublingual saliva (HSMSL) are mucins, amylases, cystatins, proline-rich proteins and statherin. Structure-function studies of these molecules have been hampered by the small amounts of purified materials that can be isolated from human secretions. The present study describes an integrated purification protocol for the large-scale preparation of many of these molecules. To dissociate partially heterotypic complexes among salivary molecules, HSMSL was initially fractionated into four pools by gel filtration with 6 M-guanidine hydrochloride. Subsequent fractionation of these four pools by gel-filtration and ion-exchange chromatography resulted in the purification of high- and low-Mr mucins, neutral and acidic cystatins, acidic and basic proline rich proteins and statherin. Many variants or isoforms of these salivary molecules have been identified and biochemically characterized. Biochemical studies indicated that the low-Mr mucin exists as two isoforms which vary in their sialic acid to fucose ratios. Three isoforms of acidic cystatin S were characterized which differ in their phosphate content. Two isoforms of a basic proline-rich peptide were identified; the smaller peptide was a truncated form missing the first seven amino acids. PMID- 1747108 TI - Selective uptake of cholesteryl esters from apolipoprotein-E-free high-density lipoproteins by rat parenchymal cells in vivo is efficiently coupled to bile acid synthesis. AB - [3H]Cholesteryl ester-labelled human high-density lipoprotein (HDL) was injected into rats and its decay, intrahepatic cellular distribution and the kinetics of biliary secretion were determined. At 10 min after injection the hepatic uptake of cholesteryl esters from HDL was 3-fold higher as compared with the apolipoprotein. Selective uptake was exerted only by parenchymal cells (5.6-fold more cholesteryl esters than apolipoprotein) and not by liver endothelial or Kupffer cells. The kinetics of biliary secretion of processed cholesteryl esters initially associated with HDL or low-density lipoprotein (LDL) were compared in unrestrained rats, equipped with permanent catheters in bile duct, duodenum and heart. At 72 h after injection of [3H]cholesteryl oleate-labelled HDL, 51.0 +/- 2.5% of the injected dose was recovered as bile acids, which is about twice as high as the secretion of biliary radioactivity after injection of [3H]cholesteryl oleate-labelled LDL. Oestradiol treatment stimulated only liver uptake of LDL cholesteryl esters, and resulted in a 2-fold higher liver uptake than with HDL. However, the rate of radioactive bile acid formation from [3H]cholesteryl oleate labelled HDL was still more rapid than for LDL. It is concluded that the selective uptake pathway for cholesteryl esters from HDL in parenchymal cells is more efficiently coupled to the formation of bile acids than is the cholesteryl ester uptake from LDL. This efficient coupling may facilitate the role of HDL in reverse cholesterol transport. PMID- 1747109 TI - Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats. AB - We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile duct ligation decreased by about 30% both the amount of microsomal cytochrome P 450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3 methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380 fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P 450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated. PMID- 1747110 TI - Studies on the activation of human neutrophil 5-lipoxygenase induced by natural agonists and Ca2+ ionophore A23187. AB - By using exogenous substrates, activation of human neutrophil 5-lipoxygenase can be investigated independently of the release of endogenous arachidonic acid. We have developed a sensitive assay to measure 5-LO activation which takes advantage of the 5-LO-mediated conversion of 15S-hydroperoxy-5,8,11,13(Z,Z,Z,E) eicosatetraenoic acid (15-HpETE) into 5S,15S-dihydroxy-6,8,11,13(E,Z,Z,E) eicosatetraenoic acid (5,15-DiHETE). When resting neutrophils were incubated with low micromolar concentrations of 15-HpETE, a minor dose- and time-dependent formation of 5,15-DiHETE was observed. In contrast, co-addition of 15-HpETE with Ca2+ ionophore A23187 or with the neutrophil agonists platelet-activating factor (PAF), fMetLeuPhe or complement component C5a resulted in a sizeable concentration-dependent synthesis of 5,15-DiHETE, while lyso-PAF and phorbol myristate acetate were without effect on 5,15-DiHETE formation from 15-HpETE. This stimulation of 5,15-DiHETE synthesis by A23187 or by natural agonists was effectively inhibited by MK-886, a compound that has recently been reported to inhibit the A23187-induced translocation of 5-LO to membrane structures. Furthermore, natural-agonist-induced activation of the 5-LO-mediated transformation of 15-HpETE was inhibited by pertussis toxin, indicating the involvement of a GTP-binding protein in the 5-LO activation process. PMID- 1747111 TI - Interaction of LY171883 and other peroxisome proliferators with fatty-acid binding protein isolated from rat liver. AB - Fatty-acid-binding protein (FABP) is a 14 kDa protein found in hepatic cytosol which binds and transports fatty acids and other hydrophobic ligands throughout the cell. The purpose of this investigation was to determine whether LY171883, a leukotriene D4 antagonist, and other peroxisome proliferators bind to FABP and displace an endogenous fatty acid. [3H]Oleic acid was used to monitor the elution of FABP during chromatographic purification. [14C]LY171883 had a similar elution profile when substituted in the purification, indicating a common interaction with FABP. LY171883 and its structural analogue, LY189585, as well as the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate, bezafibrate and WY14,643, displaced [3H]oleic acid binding to FABP. Analogues of LY171883 that do not induce peroxisome proliferation only weakly displaced oleate binding. [3H]Ly171883 bound directly to FABP with a Kd of 10.8 microM, compared with a Kd of 0.96 microM for [3H]oleate. LY171883 binding was inhibited by LY189585, clofibric acid, ciprofibrate and bezafibrate. These findings demonstrate that peroxisome proliferators, presumably due to their structural similarity to fatty acids, are able to bind to FABP and displace an endogenous ligand from its binding site. Interaction of peroxisome proliferators with FABP may be involved in perturbations of fatty acid metabolism caused by these agents as well as in the development of the pleiotropic response of peroxisome proliferation. PMID- 1747112 TI - Heterogeneous distribution of antithrombin-binding sites in rat brain heparan sulphate proteoglycans. AB - Heparan sulphates with high binding affinity for antithrombin (HA-HS), labelled in vivo with [35S]sulphate, were extracted from rat brains and purified by chromatography on DEAE-cellulose and on antithrombin-agarose. HA-HS proteoglycans (HA-HSPG) were then separated from HA-HS chains on Sepharose CL-6B. The total HA HSPG product was rechromatographed on antithrombin-agarose. Six HA-HSPG subfractions with differing degrees of affinity for antithrombin were recovered and treated with NaOH to release their chains. Rechromatography of these six 35S labelled HS chain preparations on antithrombin-agarose showed that their proportions of chains with no affinity for antithrombin (NA-HS chains) ranged from 36 to 71%. There was a reciprocal relationship between the proportion of NA HS chains in each HA-HSPG subfraction and the degree of affinity for antithrombin of the rest of its chains (assessed relative to 3H-labelled HA-heparin chains with which they were co-chromatographed). Similar characteristics of antithrombin binding-site distribution apply to HA-heparin proteoglycans from rat skin studied previously [Horner (1987) Biochem. J. 244, 693-698]. The data suggest that the sites at which 3-O-sulphation of some glucosamine N-sulphate residues occurs in the Golgi complex of brain cells (probably endothelial cells) which synthesize HA HSPGs (as in mast cells, which synthesize HA-heparin PGs) are distributed sparsely but not randomly. PMID- 1747113 TI - Immunohistochemical distribution of isoenzymes of glutathione transferase in adult rat adrenal gland before and after hypophysectomy. AB - The distribution of glutathione transferase subunits 1, 2, 3, 4, 7 and 8 in the different cells of the female and male rat adrenal and the effects of hypophysectomy on these isoenzymes were studied using immunohistochemical methods. All these glutathione transferase subunits, with the exception of subunit 1, were present in the adrenal. Each subunit showed, however, its own characteristic distribution pattern. After hypophysectomy, increased staining for these isoenzymes was generally observed, and this effect was also cell-specific. Staining for subunit 2 increased in intensity in the zona fasciculata and reticularis after hypophysectomy, whereas a decrease was observed in the zona glomerulosa. Staining for subunit 8 was increased in the borderline between the capsule and zona glomerulosa, as well as in medullary chromaffin cells after hypophysectomy. The Mu subunits 3 and 4 increased markedly in fascicular and reticular cells after hypophysectomy and staining for subunit 3 was also increased in the medullary cells. A slight, but more general, increase was observed for subunit 7. We conclude from these experiments that the increases in glutathione transferase subunits observed in the rat adrenal after hypophysectomy are due to increased protein synthesis and/or increased protein stability and not to a selective destruction of cells lacking, or with low levels of, the isoenzymes. PMID- 1747114 TI - Kinetic mechanism of Clostridium perfringens phospholipase C. Hydrolysis of a thiophosphate analogue of lysophosphatidylcholine. AB - The hydrolysis of S-[2-(hexadecanoyloxy)ethyl]thiophosphocholine (I), an analogue of lysophosphatidylcholine, by Clostridium perfringens phospholipase C, was followed at pH 7.5, 37 degrees C and I 1.0 (maintained with KCl), in a continuous assay, by monitoring the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) at 412 nm. Simple saturation kinetics are observed with linear mixed-type slope intercept effects for the hydrolysis of compound (I) with variable [Ca2+] at fixed concentrations of compound (I) and a simple slope effect as [compound (I)] is varied at fixed concentrations of Ca2+. These data are consistent with a simple ordered rapid-equilibrium mechanism in which Ca2+ binds to the enzyme first followed by substrate. The observed kinetic constants at pH 7.5, 37 degrees C and I 1.0 are K1 = 12.0 mM (Ca2+ dissociation), K2 = 36 microM [compound (I) dissociation] and Vmax. = 552 microM.min-1.mg-1. Alkane diammonium salts inhibit the enzyme by a non-competitive mechanism that involves binding to free enzyme, E.Ca2+ and E.Ca2+.S. The use of the simple micellarized substrate under these conditions allows the determination of kinetic and inhibition constants without complications arising from enzyme-micelle interactions. PMID- 1747115 TI - Interaction of the small proteoglycan decorin with fibronectin. Involvement of the sequence NKISK of the core protein. AB - Decorin, an interstitial small proteoglycan, was shown to interact with fibronectin via its core protein. In a solid-phase assay, both high-affinity (KD values between 10 and 20 nM) and low-affinity (KD values between 110 and 130 nM) binding sites were found. The central position of decorin core protein is made up of several repeats containing NKISK in positions 85-89 and similar sequences in other repeats. The pentapeptide inhibited, albeit not completely, the high affinity interaction between decorin and fibronectin in a specific charge independent manner. Half-maximal inhibition occurred at a peptide concentration of 10 microM. Core-protein-derived peptides that had been produced by endoproteinase Lys-C digestion were not inhibitory, but endoproteinase Arg-C generated peptides served as inhibitors of binding. These results suggest that NKISK as a component of repetitive sequences of decorin is involved in the interaction between the proteoglycan and fibronectin. PMID- 1747116 TI - Effects of lactate on pathways of glycogen formation in the perfused rat liver. AB - In order to investigate the roles of lactate as substrate and regulator of hepatic glycogen synthesis, two groups of rat livers were perfused with oxygenated blood for 2 h. The initial perfusate glucose and lactate concentrations of Group I and II were 245 +/- 6.8 and 254 +/- 12.9 mg/dl and 49 +/- 2.6 and 54 +/- 2.2 mg/dl respectively. Labelled glucose was added to the perfusate to assess direct glycogen formation. Either additional glucose (Group I) or lactate (Group II) was added (1 mg/min) to a recirculating liver-perfusion system. Initial lactate uptake and glucose formation was identical in the two groups of studies. For Group I, both glucose and lactate uptake by the liver fell to nearly zero, in spite of increasing glucose concentrations. However, with lactate infusion (Group II), its uptake by the liver was maintained at 0.89 +/- 0.14 mg/min after 120 min. In total, 6.2 +/- 0.7 mg (Group I) or 20.2 +/- 3.9 mg (Group II) of glycogen was formed, 4.0 +/- 0.7 mg or 9.2 +/- 2.0 mg by direct synthesis from glucose and 2.2 +/- 0.3 mg or 11.0 +/- 2.1 mg by gluconeogenic formation, in Groups I and II respectively. With the provision of additional lactate, its uptake by the perfused liver tripled, as did glycogen synthesis. Glucose production doubled when lactate was added instead of glucose. Gluconeogenic formation of glycogen increased by 400%. Surprisingly, direct synthesis from glucose also rose by 130%. These data indicate that continued lactate uptake by the liver with gluconeogenic glycogen formation determines the amount of glycogen formed not only by this route, but also by direct synthesis from glucose. PMID- 1747117 TI - Fluorimetric assay of the neurotensin-degrading metalloendopeptidase, endopeptidase 24.16. AB - Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp (Mcc = 3-carboxy-7-methoxycoumarin; Dnp = dinitrophenyl), a quenched fluorimetric substrate originally designed as a probe to measure Pz-peptidase (also called endopeptidase 24.15), was examined as a putative substrate of the neurotensin-degrading neutral metalloendopeptidase, endopeptidase 24.16. During the purification of endopeptidase 24.16 the neurotensin(1-10) and neurotensin(11-13) formation due to this enzyme was coeluted with Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp-hydrolysing activity. By both fluorimetric and h.p.l.c. analyses, we observed that the latter activity was dose dependently and completely abolished by neurotensin with an IC50 value (2.6 microM) that closely corresponds to the affinity of purified endopeptidase 24.16 for neurotensin (Km = 2.5 microM). Furthermore, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp hydrolysis was inhibited by a series of dipeptides with a rank of order of potencies that parallels that observed in competition experiments of tritiated neurotensin hydrolysis by brain and intestinal endopeptidase 24.16. Altogether, these data clearly demonstrate that, in addition to Pz-peptidase, Mcc-Pro-Leu-Gly Pro-D-Lys-Dnp also behaves as a substrate of endopeptidase 24.16, with a Km of about 26 microM. In addition, we show that, even in crude membrane preparations, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp behaves as a useful tool to monitor and accurately quantify endopeptidase 24.16. PMID- 1747118 TI - Synthesis and secretion of a cobalamin-binding protein by HT 29 cell line. AB - An HT 29 cell line derived from human colonic carcinoma was shown to synthesize and release a cobalamin-binding protein. The cobalamin-binding protein was classified as transcobalamin (TC). By gel filtration on Sephacryl S200 HR, we observed that the secreted protein bound to cobalamin had the same size as plasma transcobalamin. Like transcobalamin, the cobalamin-binding protein bound cobalamin but not cobinamide. Purification of the cobalamin-binding protein was performed by heparin-Sepharose affinity chromatography and by Sephacryl S200 gel filtration. The molecular mass of the purified protein was estimated at 44 kDa by SDS/PAGE. The isoelectric point was determined to be 6.4. The purified cobalamin binding protein reacted with an antiserum produced against human transcobalamin. A 44 kDa band was also identified by SDS/PAGE of an immunoprecipitated homogenate from HT 29 cells labelled with [35S]methionine and in a Western blot of cell homogenates. The secretion of the cobalamin-binding protein was maximal between 10 and 12 days of cell culture and was inhibited by cycloheximide. PMID- 1747119 TI - The regulation of phospholipase D activity and its role in sn-1,2-diradylglycerol formation in bombesin- and phorbol 12-myristate 13-acetate-stimulated Swiss 3T3 cells. AB - Addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) to quiescent Swiss 3T3 cells resulted in a sustained increase in sn-1,2-diradylglycerol (DG) mass and [3H]DG in [3H]palmitate-labelled cells where phosphatidylcholine was the major labelled phospholipid. This occurred in the absence of inositol phosphate accumulation. In [3H]palmitate-labelled cells both bombesin and PMA stimulated the formation of phosphatidylbutanol ([3H]PtdBut) in the presence of 0.3% (v/v) butan-1-ol. The kinetics of [3H]PtdBut formation were consistent with phospholipase D (PLD) activation preceding sustained DG formation. The inclusion of butan-1-ol inhibited 70% of PMA-stimulated DG formation but only 30% of the bombesin response. The ability of bombesin and PMA to stimulate the accumulation of [3H]PtdBut was completely abolished in Swiss 3T3 cells which had been pre treated with 400 nM-PMA for 48 h to down-regulate protein kinase C activity. PMA stimulated [3H]PtdBut formation was inhibited by 90% by the protein kinase C inhibitor Ro-31-8220 (10 microM), but bombesin-stimulated PtdBut accumulation was inhibited by at most 50% by the same concentration of inhibitor. Cyclic AMP elevating agents, i.e. forskolin, dibutyryl cyclic AMP and isobutylmethylxanthine, did not inhibit bombesin stimulation of PLD activity. Bombesin-stimulated PLD activity was inhibited by 50% by buffering of the extracellular Ca2+ concentration to 150 nM, but combination of this treatment with Ro-31-8220 addition was less than additive. Ionophore A23187 alone was able to stimulate PLD activity, but this response was inhibited 50% by Ro-31-8220. Thapsigargin was unable to stimulate PLD activity and had no modulatory effect upon bombesin-stimulated PLD activity at any agonist concentration. The results are discussed in terms of the role of PLD in DG generation and the regulation of PLD activity both by bombesin and by PMA. PMID- 1747120 TI - Mutagenesis of arginine residues in the catalytic cleft of Escherichia coli porphobilinogen deaminase that affects dipyrromethane cofactor assembly and tetrapyrrole chain initiation and elongation. AB - Substitutions of conserved arginine residues in the catalytic cleft of Escherichia coli porphobilinogen deaminase were constructed by site-specific mutagenesis of the hemC gene. Mutant proteins exhibited a range of defects including the failure to assemble the dipyrromethane cofactor and the inability to initiate and propagate the tetrapolymerization reaction. Mutations of arginine residues at positions 11, 131, 132 and 155, all of which interact with the carboxylic acid side chains of the dipyrromethane cofactor, were the most disruptive. PMID- 1747121 TI - The Enterococcus hirae R40 penicillin-binding protein 5 and the methicillin resistant Staphylococcus aureus penicillin-binding protein 2' are similar. AB - The penicillin-resistant Enterococcus hirae R40 has a typical profile of membrane bound penicillin-binding proteins (PBPs) except that the 71 kDa PBP5 of low penicillin affinity represents about 50% of all the PBPs present. Water-soluble tryptic-digest peptides were selectively produced from PBP5, their N-terminal regions were sequenced and synthetic oligonucleotides were used as primers to generate a 476 bp DNA fragment by polymerase chain reaction. On the basis of these data, the PBP5-encoding gene was cloned in Escherichia coli by using pBR322 as vector. The gene, included in a 7.1 kb insert, had the information for a 678 amino acid-residue protein. PBP5 shows similarity, in the primary structure, with the high-molecular-mass PBPs of class B. In particular, amino acid alignment of the enterococcal PBP5 and the methicillin-resistant staphylococcal PBP2' generates scores that are 30, for the N-terminal domains, and 53, for the C terminal domains, standard deviations above that expected for a run of 20 randomized pairs of proteins having the same amino acid compositions as the two proteins under consideration. PMID- 1747122 TI - Purification and characterization of cephalosporin 7 alpha-hydroxylase from Streptomyces clavuligerus. AB - Cephalosporin 7 alpha-hydroxylase, which catalyses the conversion of cephalosporins into their 7 alpha-hydroxy derivatives, was purified nearly 390 fold from Streptomyces clavuligerus through ion-exchange chromatography, (NH4)2SO4 fractionation, gel filtration and dye chromatography, with the use of h.p.l.c. to monitor enzyme activity. The nearly pure enzyme migrates as a single major band, with an Mr of 32,000 in SDS/PAGE. Its optimum pH is in the range 7.3 7.7. Under our conditions the reaction was fastest at temperatures in the range 20-30 degrees C. The Km for cephalosporin C is 0.72 mM, and the Vmax. is 15.4 mumol of cephalosporin C hydroxylated/min per mg. Cephalosporin 7 alpha hydroxylase did not show any deacetoxycephalosporin C synthase or deacetoxycephalosporin C hydroxylase activity. PMID- 1747123 TI - Methanol oxidation and assimilation in Hansenula polymorpha. An analysis by 13C n.m.r. in vivo. AB - The metabolism of methanol was monitored in whole cells of the methylotrophic yeast Hansenula polymorpha by using [13C]methanol and n.m.r. in vivo. The main products observed under normal conditions were trehalose and glycerol, whereas cells that were starved before exposure to [13C]methanol also accumulated glutamate, glutamine and alanine; formate was also more prominent in spectra from starved cells. Cells exposed to high methanol concentration together with high oxygenation oxidized methanol extensively, leading to formaldehyde accumulation; label was not found in any subsequent metabolic products, indicating possible cell inactivation. [13C]Formate was incorporated into metabolic products in glucose-grown cells exposed to 150 mM-methanol for 3 h, but not in cells starved for 3 h, in which it was oxidized. At 21 degrees C such 3 h-starved cells showed a slower metabolism of [13C]methanol compared with those at 37 degrees C, and also converted methanol into formate rather than into assimilation products. The labelling pattern in trehalose from starved cells at 37 degrees C was consistent with methanol assimilation via the pentose phosphate pathway. Lack of appearance of labelled formaldehyde and formate during metabolism under normal conditions suggests that the linear oxidation pathway is not a major contributor to methanol oxidation; their appearance in extreme conditions suggests instead a more likely role in detoxification. PMID- 1747124 TI - Characterization and chromatin distribution of the H1 histones and high-mobility group non-histone chromosomal proteins of trout liver and hepatocellular carcinoma. AB - The H1 histones serve as general repressors of gene expression by inducing the formation of a compact chromatin structure, whereas the high-mobility-group (HMG) non-histone chromosomal proteins have roles in maintaining the structure and function of transcriptionally active chromatin. The distribution of the H1 histone subtypes and HMG proteins among various trout tissues (liver, hepatocellular carcinoma, testis and erythrocyte) was determined. Histone H1b was present in the chromatin of liver, but not in the chromatin of hepatocellular carcinoma, testis or erythrocyte. Nuclease-resistant regions of liver chromatin had elevated levels of histone H1b. Histone H1b was isolated, and the N-terminal amino acid sequence of histone H1b was found to be highly similar to that of mammalian histone H1(0) and duck H5. HMG proteins T1, T2, T3, H6, C, D and F were associated with liver and hepatocellular-carcinoma chromatin, with hepatocellular carcinoma containing higher levels of HMG T1 and F. Testis and erythrocyte had HMG T2 and H6 as their predominant HMG proteins. Most of the HMG H6 of hepatocellular carcinoma, but not of liver, was located in a chromatin fraction that was soluble at physiological ionic strength and enriched in transcriptionally active DNA. These alterations in the chromatin distribution and content of hepatocyte HMG proteins and H1 histone subtypes may contribute to aberrant hepatocyte gene expression in the hepatocellular carcinoma. PMID- 1747125 TI - Accumulation of acyl-enzyme in DD-peptidase-catalysed reactions with analogues of peptide substrates. AB - Thioester substrates can be used to study the hydrolysis and transfer reactions catalysed by beta-lactamases and DD-peptidases. With the latter enzymes, accumulation of the acyl-enzyme can be detected directly. The efficiency of various amines as acceptor substrates was in excellent agreement with previous results obtained with peptide substrates of the DD-peptidases. The results indicated the presence of a specific binding site for the acceptor substrates. Although most of the results agreed well with a simple partition model, more elaborate hypotheses will be needed to account for all the data presented. PMID- 1747126 TI - Ricinoleic acid biosynthesis and triacylglycerol assembly in microsomal preparations from developing castor-bean (Ricinus communis) endosperm. AB - Microsomal membrane preparations from the developing endosperm of castor bean (Ricinus communis) catalysed the transfer of oleate from [14C]oleoyl-CoA to phosphatidylcholine (PtdCho). In the presence of NADH, radioactive ricinoleate (12-hydroxyoctadec-9-enoate) was synthesized from [14C]oleate, and this was largely recovered in PtdCho and as free fatty acid. The addition of unlabelled ricinoleoyl-CoA to these incubation mixtures did not increase the low [14C]ricinoleate concentration found in the acyl-CoA fraction nor decrease the [14C]ricinoleate concentration in PtdCho and free fatty acid, and thus no evidence was obtained for a hydroxylation with oleoyl-CoA as a substrate. The addition of NADH, necessary for the formation of ricinoleate, caused a decrease of the total radioactivity in PtdCho with a corresponding increase in the amount of label in free ricinoleic acid. This increase was due to the action of a phospholipase A, which released ricinoleic acid but not oleic acid from PtdCho. Such a phospholipase activity, attacking ricinoleoyl-PtdCho but not oleoyl PtdCho, was also demonstrated in microsomal preparations from developing cotyledons of safflower and oil-seed rape. An analysis of the acyl groups at different positions in microsomal PtdCho of castor bean showed that ricinoleate was almost entirely associated with position sn-2. Likewise the [14C]ricinoleate in [14C]PtdCho formed after incubations with microsomal preparations with NADH and [14C]oleoyl-CoA resided in position sn-2 with none in position sn-1. In contrast, the [14C]linoleate formed by desaturation of [14C]oleoyl-PtdCho was present at both positions. In the presence of ATP, CoA and Mg2+, the ricinoleate acid released from PtdCho was activated to ricinoleoyl-CoA. The ricinoleoyl-CoA was an efficient acyl donor in the acylation of glycerol 3-phosphate (Gro3P) to yield phosphatidic acid and triacylglycerols. In microsomal preparations incubated with an equimolar mixture of [14C]oleoyl-CoA and [14C]ricinoleoyl-CoA in the presence of Gro3P, only a minor amount of [14C]ricinoleate entered PtdCho, and this was believed to be via the exchange of phosphocholine groups between a diacylglycerol pool and the PtdCho. On the basis of our results, a scheme of ricinoleate formation and its incorporation into triacylglycerols in castor-bean endosperm is proposed. PMID- 1747127 TI - Inhibition by pertussis toxin of the activation of Na(+)-dependent uridine transport in dimethyl-sulphoxide-induced HL-60 leukaemia cells. AB - The effects of pertussis toxin on the Na(+)-dependent transport of uridine were studied in HL-60 leukaemia cells induced to differentiate along the granulocytic or monocytic pathways by dimethyl sulphoxide (DMSO) or phorbol 12-myristate 13 acetate (PMA) respectively. Pertussis toxin at 50 ng/ml completely inhibited the activation of Na(+)-dependent uridine transport and consequently prevented the formation of intracellular pools of free uridine which occurs in HL-60 cells induced to differentiate by DMSO. The inhibition of Na(+)-dependent uridine transport by pertussis toxin in cells exposed to DMSO was associated with a 14 fold decrease in affinity, with no change in Vmax. Pertussis toxin, however, had no effect on Na(+)-dependent uridine transport in PMA-induced HL-60 cells. Furthermore, 500 ng of cholera toxin/ml had no effect on the Na(+)-dependent uptake of uridine in DMSO-treated HL-60 cells. These results suggest that the activation of the Na(+)-dependent transport of uridine in HL-60 cells induced to differentiate along the granulocytic pathway by DMSO is coupled to a pertussis toxin-sensitive guanine-nucleotide binding protein (G-protein). PMID- 1747128 TI - Aluminium transport in blood serum. Binding of aluminium by human transferrin in the presence of human albumin and citrate. AB - The binding of Al3+ by human serum transferrin has been investigated by u.v. visible difference spectroscopy. In the presence of 25 mM-HCO3- at pH 7.4, the apparent association constants were found to be 1.69 x 10(12) M-1 and 5.36 x 10(11) M-1. These association constants are pH-dependent, reducing with both increasing and decreasing pH. The apparent pKa values were found to be 6.7 and 8.2. Competitive assays of binding of Al3+ to transferrin in the presence of citrate and human serum albumin at molar ratios corresponding to those found in normal plasma showed that a considerable amount of Al3+ was not bound to transferrin. Taking a concentration of 5 microM as a typical value observed for the plasma of patients on haemodialysis [Harris & Sheldon (1990) Inorg. Chem. 29, 119-124] the competitive binding assay indicate that approximately 60% of it is bound to transferrin, approximately 34% to albumin and the remainder to citrate. These results therefore suggest that, although transferrin at pH 7.4 is the major Al(3+)-binding component of plasma, an appreciable amount of Al3+ present in patients on haemodialysis may be bound to albumin. PMID- 1747129 TI - Effects of platelet-activating factor on lipid metabolism in rats in vivo. Origin of the hypertriglyceridaemia. AB - Administration of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine; PAF) did not alter the rate of triacylglycerol entry into the plasma. The gastrointestinal absorption of [1-14C]triolein was, however, inhibited by PAF, yet there was increased accumulation of [14C]lipid in the plasma and hypertriglyceridaemia. The half-life of injected [9,10(n)-3H]triolein in the plasma increased by 47%, and there was decreased accumulation of [3H]lipid in brown adipose tissue. This was accompanied by a decrease in lipoprotein lipase activity. The hypertriglyceridaemia induced by PAF appears to be mainly due to decreased peripheral removal, one important site affected being brown adipose tissue. PMID- 1747130 TI - Progressive suppression of muscle glucose utilization during pregnancy. AB - Glucose utilization indices (GUIs) were measured in heart and a range of skeletal muscles in conscious, unrestrained, virgin or pregnant rats in the absorptive and post-absorptive phases. A clear effect of pregnancy to diminish muscle GUIs was identified, the magnitude of which was greatest in late gestation in the absorptive phase. Differences in the time courses and magnitudes of the response to pregnancy were observed between individual muscles. The effects of pregnancy are discussed in relation to an increased availability of lipid fuels and to decreased insulin and glucose concentrations. PMID- 1747131 TI - Anomalous behaviour of a protein during SDS/PAGE corrected by chemical modification of carboxylic groups. AB - The 29,000-Mr Actinomadura R39 beta-lactamase exhibited a remarkably low electrophoretic mobility on SDS/PAGE, yielding an Mr value almost twice that computed from the corresponding gene sequence. We showed that chemical modification of the carboxylic groups of glutamic acid and aspartic acid residues restored a normal electrophoretic mobility and that the anomalous behaviour of that protein on SDS/PAGE was due to its very large negative charge at neutral pH. We also compared the behaviour of the same enzyme on gel filtration in the presence of SDS with those of other class A beta-lactamases (Mr approx. 30,000). These experiments suggested that the very low electrophoretic mobility of the Actinomadura R39 beta-lactamase upon SDS/PAGE was more probably due to a low degree of SDS binding rather than to an unusual shape of the SDS-protein complex. PMID- 1747132 TI - Allosteric regulation of phosphonoacetaldehyde hydrolase by n-butylphosphonic acid. AB - The effect of n-butylphosphonic acid on the activity of phosphonoacetaldehyde hydrolase from Pseudomonas aeruginosa was investigated: at low concentrations this compound appeared as an activator of the enzyme activity, whereas at higher concentrations it exhibited inhibitory properties. The experimental results were modelled according to an allosteric model involving two different classes of sites for n-butylphosphonic acid. PMID- 1747133 TI - Influence of antihyperuricemic therapy on the clinical and radiographic progression of gout. AB - Ten years ago, we studied the clinical and radiographic manifestations of gout in 60 patients and described 3 patterns of disease. To determine the consequences of management over a 10-year period, we recently reassessed the 39 available patients of this population. We found that although reduced tophaceous deposition on physical examination correlated with normalization of the serum urate concentration, no correlation existed between radiographic changes and mean serum urate concentrations. Progression of gouty changes on radiography reflected progressive deformity on physical examination. We have described the radiographic changes that occurred in a well-characterized population of subjects with gout over 10 years and determined that serum urate concentrations alone may not provide an effective means of monitoring the progression of tophaceous disease in bone. PMID- 1747134 TI - Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washington, 1987-1989. AB - As part of a prospective case-control study of newly diagnosed rheumatoid arthritis (RA) in women, we identified all cases of probable, definite, or classic RA diagnosed in 1987-1989 in 18-64-year-old women who were members of a health maintenance organization based in the Seattle, Washington area. Using both the 1958 and the 1987 American Rheumatism Association criteria for the diagnosis of RA and enrollment data from the health maintenance organization, we calculated the incidence by age and diagnostic class. Rates of RA incidence in women increased steadily with age. The incidence of probable, definite, or classic RA ranged from 13.1 per 100,000 person-years at risk for 18-29-year-old women to 82.1 per 100,000 person-years for 60-64-year-old women. The overall incidence rate, age-adjusted to the 1980 US female population, was 27.9/100,000 person years. The overall incidence rate for definite/classic RA, age-adjusted to the 1980 US female population, was 23.9 per 100,000 person-years. When compared with adjusted rates of incidence of definite RA in Rochester, Minnesota, in 1950-1974, the incidence rates we found were 44.7% lower. Methodologic differences, changes in diagnostic criteria, and a declining incidence of RA among women over time may all be partial explanations for these results. The possible effects of reproductive factors, including oral contraceptives use, are discussed. PMID- 1747135 TI - A comparative study by morphometry of the microvasculature in normal and rheumatoid synovium. AB - Vascularity is said to be increased (subjectively) in rheumatoid arthritis, yet synovial fluid is hypoxic and acidotic. Morphometry by image analysis was used to quantify vascularity in normal and rheumatoid synovium from the knee joint. Capillaries were distributed more deeply in the rheumatoid synovium (93.3 microns, compared with 32.5 microns in normal synovium) and were significantly less densely arranged (80.2/mm2 rheumatoid, 241.5/mm2 normal). The blood volume fraction fell from 2.9% in normal knee synovium to 1.2% in rheumatoid synovium. These results imply that there is impairment of O2 transfer, which contributes to the intraarticular hypoxia, in rheumatoid arthritis. PMID- 1747136 TI - Aspirin alters methotrexate disposition in rheumatoid arthritis patients. AB - Intravenous methotrexate (MTX) (10 mg), either alone or with oral aspirin (ASA) (3,900 mg/day), was administered to 15 patients with rheumatoid arthritis. Systemic and renal clearance of MTX were lower, and the unbound fraction of MTX was higher when patients were also receiving ASA than when taking MTX alone. No acute hematologic, renal, or hepatic toxicity was observed with either treatment. The findings of this study therefore indicate that concomitant aspirin therapy acutely alters the clearance of low-dose MTX in patients with rheumatoid arthritis. PMID- 1747137 TI - Absorbed dose profiles for radionuclides of frequent use in radiation synovectomy. AB - Absorbed dose profiles are presented for radionuclides of frequent or potential use in radiation synovectomy, an intraarticular technique aimed at treating rheumatoid arthritis through direct and highly selective irradiation of inflamed synovium. The radionuclides investigated were 198Au, 165Dy, 32P, 186Re, 90Y, and 166Ho. These profiles reveal the absorbed dose imparted per unit activity of injected radionuclide (Gy/mCi) as a function of penetration distance (mm) to major components of the arthritic synovial joint. Their usefulness is twofold: they can be employed to select the radionuclide best suited to achieving the proper depth of penetration in tissue (approximating the thickness of the inflamed synovium) and to determine, a priori, the necessary dose of radioactivity (delivering an absorbed dose sufficient to effectively treat all the diseased tissue). The extent of radiation of other synovial joint components, such as bone and articular cartilage, and how the advancing rheumatoid arthritis can be expected to alter the extent and pattern of absorbed dose penetration in the joint are also discussed. PMID- 1747138 TI - Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis. AB - To determine whether complement turnover in synovial fluids of patients with rheumatoid arthritis (RA) reflects activation by the classical or alternative pathway, we used novel immunoassays to measure products of complement activation (the membrane attack complex SC5b-9 and the cleavage fragments Bb and C4d). Mean synovial fluid levels of SC5b-9 were more than 8 times higher in RA than in crystal-induced arthritis (gout and pseudogout) and over 16 times higher than in degenerative joint disease (DJD). Similarly, Bb levels were more than 3 times higher in RA synovial fluids than in crystal-induced arthritis and over 7 times higher than in DJD. Levels of C4d did not differ among the groups. SC5b-9 levels correlated with synovial fluid C3 anaphylatoxin (C3a), Bb, and C4d levels (r = 0.81, 0.62, and 0.51, respectively). In patients with RA, synovial fluid SC5b-9 levels correlated with C3a and Bb (r = 0.6 and 0.56, respectively) but not with C4d. Therefore, novel assays for complement activation indicate that both classical and alternative pathways are involved in complement turnover and that the alternative pathway contributes more to complement activation in RA than in DJD or crystal-induced arthritis. PMID- 1747139 TI - Continuous removal of anti-DNA antibody, using a new extracorporeal immunoadsorption system, in patients with systemic lupus erythematosus. AB - We performed selective and continuous immunoadsorption of anti-DNA antibodies from the blood of 6 patients with systemic lupus erythematosus, using a newly developed extracorporeal immunoadsorption system equipped with twin dextran sulfate-cellulose columns with an automated regenerating unit. Levels of anti DNA, which were initially high, were rapidly diminished after 2-4 apheresis procedures in each patient; in 3 patients with proteinuria and 4 patients with lymphocytopenia, these symptoms also improved. Analysis of the kinetics and the adsorbed amounts of anti-DNA during the apheresis indicates that both the intravascular and the extravascular pool of anti-DNA are reduced with this potent apheresis technique. PMID- 1747140 TI - Malignant histiocytosis as a fatal complication of systemic lupus erythematosus. AB - We present the case of a 26-year-old Caucasian woman with systemic lupus erythematosus (SLE) of 9 years duration, mainly involving the kidney. Her clinical course was complicated in the last year by several infectious and noninfectious events, and after pancytopenia, fever, and extremely high levels of lactate dehydrogenase developed, the woman died. Light and electron microscopy of bone marrow, together with immunophenotyping, disclosed malignant histiocytosis, a complication of SLE that has not been reported. PMID- 1747141 TI - Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament. AB - Anterior cruciate ligament transection (ACLT) in the dog results in osteophyte formation and in morphologic, metabolic, biochemical, and biomechanical changes in the articular cartilage of the unstable knee that mimic those of human osteoarthritis (OA). However, in dogs studied up to 2 years after ACLT, the changes have appeared to be self-limiting, which has led to the suggestion that this is a model of cartilage damage and repair, rather than of OA. To ascertain whether changes in articular cartilage and subchondral bone of dogs subjected to ACLT lead to progressive changes of OA, we studied 3 dogs for 54 months after ACLT. Arthrotomy was performed in the dogs to visualize and then transect the anterior cruciate ligament. When the dogs were killed, full-thickness ulceration of the articular cartilage was seen on the medial femoral condyle and tibial plateau of the unstable knee, while cartilage in other regions was thicker than that of the contralateral knee, consistent with hypertrophic cartilage repair. Synovial infiltration by mononuclear cells was not more severe than that seen in dogs killed at earlier intervals after ACLT, although gross fibrotic thickening of the capsule was apparent in each dog. Histomorphometric studies revealed a marked increase in subchondral bone volume and active bone formation. These findings show that the changes that develop in the canine knee joint after ACLT are progressive and are unambiguously those of OA. PMID- 1747142 TI - Temporal arteritis with low erythrocyte sedimentation rate: a review of five cases. AB - We compared 5 patients who had biopsy-proven temporal arteritis and erythrocyte sedimentation rates (ESR) less than 50 mm/hour with 25 patients who had temporal arteritis and high ESR and with 10 patients who had negative temporal artery biopsy results and low ESR. Patients with low-ESR temporal arteritis were similar to the other groups, except that they had a higher mean hemoglobin level than the high-ESR group and a significant increase in the percentage of patients (4 of 5) who had a previous diagnosis of polymyalgia rheumatica or had received steroid therapy compared with either of the other groups. The latter finding suggests that even low-dose steroid therapy can lower the ESR in patients with temporal arteritis. We conclude that the ESR is low in only a small percentage of patients with temporal arteritis, and that most of these patients have a history of polymyalgia rheumatica or steroid therapy. PMID- 1747143 TI - Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis. AB - We describe a 16-year-old girl with systemic-onset juvenile arthritis who presented with pulmonary hypertension, without evidence of pleural or parenchymal involvement of the lung, pulmonary vasculitis, or immune deposition in the pulmonary vasculature. Pleuropulmonary involvement occurs occasionally in juvenile arthritis, but primary pulmonary hypertension has not, to our knowledge, been previously reported. Histocompatibility typing showed positivity for HLA-DR3 and DRw52, both of which are associated with idiopathic pulmonary hypertension in children, and with pulmonary hypertension among patients with systemic sclerosis. Treatment with cyclosporine and corticosteroids resulted in a marked improvement in the clinical findings and pulmonary function in our patient. PMID- 1747144 TI - Serial magnetic resonance imaging in juvenile dermatomyositis. AB - Magnetic resonance imaging (MRI) was used to follow the course of juvenile dermatomyositis from the onset of disease through resolution of a primary relapse. The signal intensity of the T2-weighted image of involved muscles was elevated during periods of disease activity, and returned to approximately normal levels with effective suppression of disease activity. T1-weighted images of involved muscles remained approximately normal despite disease activity. PMID- 1747145 TI - Erosive arthritis in monoclonal gammopathy of uncertain significance: report of four cases. AB - We report 4 case histories in which an erosive arthritis was associated with the presence of a monoclonal gammopathy of uncertain significance. In all 4 cases, the appearance of paraprotein was noted either before or during the development of the arthritis. Two patients had a rather atypical oligoarthritis, while the others had a rheumatoid-like, symmetric polyarthritis. A synovial amyloid deposit was present in 2 patients, while mild mixed mononuclear infiltrates were the main pathologic finding in the others. In 2 patients, immunohistochemical investigation demonstrated deposits of immunoglobulin-derived material of the same isotype as the monoclonal component in the synovial tissue. PMID- 1747146 TI - Induction of arthritis in rats by soluble peptidoglycan-polysaccharide complexes produced by human intestinal flora. AB - Peptidoglycan-polysaccharide complexes were isolated from feces of a healthy subject and from ileostomy fluid from 5 patients. Peptidoglycan-polysaccharide complexes were tested for arthritogenicity in a rat model, by subcutaneous injection in Freund's incomplete adjuvant. Complexes from the healthy subject did not induce arthritis, but those from ileostomy fluid of 1 of the patients induced severe, chronic joint inflammation. We concluded that peptidoglycan polysaccharide complexes from intestinal flora are potentially arthritogenic in rats. This arthritogenicity may be influenced by the content of muramic acid and rhamnose in these complexes. PMID- 1747147 TI - Development of rheumatoid arthritis after hepatitis C virus infection. PMID- 1747148 TI - Multicenter double-blind trial of interferon-gamma versus placebo in the treatment of rheumatoid arthritis. PMID- 1747149 TI - Soluble interleukin-2 receptor in patients with ankylosing spondylitis. PMID- 1747150 TI - Reconsideration of the risk of post-arthroplasty infection in patients treated with methotrexate. PMID- 1747151 TI - Who pays for nonprofit? PMID- 1747152 TI - Why choose a nonprofit community speech and hearing center setting? PMID- 1747153 TI - Keeping the promise to those who serve. The VA Healthcare System. PMID- 1747154 TI - Third-party billing for school services. The schools' perspective. PMID- 1747155 TI - Hodgkin's disease. Treatment of the young child. AB - Age of a patient when afflicted with Hodgkin's disease is an important prognostic factor. Although there are histologic and stage differences as a function of age, the younger a patient is when diagnosed, the better the cure rate. Youngsters less than age 10 years have a freedom from relapse of 80% at 26 years follow-up examination; adolescents in the 11 to 16 age group have a freedom from relapse or 74%; and adults aged 17 years or older have a freedom from relapse of 64%. These differences translate into significant survival differences as well, with children aged 10 years or younger and those aged 11 to 16 years having a 26-year survival of 74%, as compared to adults, who have a 37% survival (P = 0.003). These differences remain significant when comparing those with stage I and II disease, as opposed to those with advanced stage III and IV disease. Children present the greatest challenges with respect to staging and treatment. The older child with localized disease can be managed appropriately as an adult. However, for the younger child the use of low-dose radiation and multiagent chemotherapy is widely accepted. Using this approach, survival rates of 85% or greater are reported from many large institutional and cooperative group experiences. The goals of treatment today are cure of disease, with maximal quality of life and minimal complications from the treatment. The late effects of greatest importance to the youngest children are skeletal and bone growth abnormalities, sterility, and malignant tumor induction. Treatment programs today should be directed towards refining therapy to minimize sequelae while maximizing quality of life. These goals are best achieved when children are managed in regional centers with demonstrated expertise in the management of children with Hodgkin's disease. Whereas cure can be achieved in a large majority of children diagnosed with Hodgkin's disease, our challenge is cure, with the least sequelae and the greatest quality of life. "Children are not simply micro-adults, but have their own specific problems." PMID- 1747156 TI - Temporal behavior of peripheral organ distribution volume in mammillary systems. PMID- 1747157 TI - Crystallization and preliminary X-ray diffraction data of the Fab fragment of a monoclonal antibody against apamin, a bee venom neurotoxin. AB - Fab fragments of anti-apamin monoclonal antibodies have been purified to homogeneity and crystallized. The crystals belong to the monoclinic space group P21 with cell dimensions a = 99.0 +/- 0.3 A, b = 137.1 +/- 0.4 A, c = 76.0 +/- 0.2 A and beta = 92.9 +/- 0.9 degrees. They most likely contain four molecules in the asymmetric unit (Vm = 2.39 A3/Da). The possibility of the existence of non crystallographic symmetry is discussed. PMID- 1747159 TI - A multidisciplinary approach to cardiac rehabilitation. AB - As health care professionals we believe rehabilitation and patient education should commence on admission and continue through to discharge. Ideally it should be started from birth, with education by the family, school, GPs and well person clinics. This should include family screening an awareness of health and factors which may affect this. When patients develop angina, support should be given so that they can control the effects more adequately and reduce potential risk factors. There should be no exclusion criteria for patients accepted on these programmes as those who would probably be excluded are those who would require rehabilitation the most. Every individual can participate in discussion and any form of exercise can be tailored to meet the individual's needs. Many benefits have been mentioned, but the most important one is the improved quality of life for the patient and her or his family. Cardiac rehabilitation programmes and self help groups may provide additional support to the patient and family during convalescence. Group programmes through their dynamics help to overcome feelings of isolation. Patients feel they gain support from their peer-group and they in turn can help each other overcome residual symptoms and practical difficulties. This 'social' rehabilitation is often the most beneficial aspect of the course; the group really helps them succeed. Rehabilitation must be accepted as part of the treatment and not a luxury for a few patients. This is a very exciting time when interest in this area is developing and research is examining the quality of life. We need to evaluate continually and undertake research to improve nursing practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747158 TI - Neuropeptide Y inhibits nicotinic cholinergic currents but not voltage-dependent calcium currents in bovine chromaffin cells. AB - The effects of neuropeptide Y (NPY; 1-36) and NPY fragment (16-36) on nicotinic currents (IACh) and voltage-dependent calcium currents (ICa) were studied in bovine chromaffin cells using the whole-cell patch-clamp technique. The peak amplitude of inward nicotinic currents was markedly depressed by both NPY (1-36) and NPY (16-36). In contrast, ICa was unaffected by either NPY (1-36) or NPY (16 36). Both pertussis toxin pretreatment and including GDP [beta-S] in the patch pipette solution completely abolished the inhibitory effect of NPY on IACh. It is concluded that inhibition of IACh probably represents the mechanism by which NPY decreases catecholamine release from adrenal medulla. This effect appears to be mediated by a G-protein-coupled Y2 receptor. PMID- 1747160 TI - The mouse proline-rich protein MP6 promoter binds isoprenaline-inducible parotid nuclear proteins via a highly conserved NFkB/rel-like site. AB - Proline-rich protein (PRP) gene MP6 was isolated from a mouse BALB/c genomic DNA library in lambda EMBL3, characterised by hybridisation and restriction mapping and the promoter region, from -162 to +72 around the PRP consensus cap-site, was sequenced. In gel shift assays this region formed complexes C1 and C2 with parotid nuclear proteins which were induced by the beta-adrenergic agonist isoprenaline. DNA competition studies and direct binding assays of promoter subfragments showed that it was the sequence from -157 to -91 that was forming the isoprenaline-dependent complexes. All PRP genes conserve a 23bp. sequence, termed PRP Box1, with ets and NFkB/rel binding site-like elements, upstream of their promoters. In the MP6 promoter, PRP Box1 was within the region forming the complexes. Further gel shift assays using PRP Box1 oligonucleotides as competitors and targets indicated that the NFkB/rel binding site-like element was important in formation of the isoprenaline-inducible complexes. HeLa nuclear extracts also formed complexes with PRP Box1 similar to C1 and C2 but nuclear extracts from spleen, submandibular gland and liver did not. These complexes are thus candidate regulators for the isoprenaline-dependent and tissue-specific transcription of PRP genes. PMID- 1747161 TI - Clozapine and loxapine for schizophrenia. PMID- 1747162 TI - The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells. AB - Recent evidence indicates that the transmembrane form of IgM on murine and human B lymphocytes is physically associated with at least two proteins, forming a disulfide-linked dimer, which may control cell surface expression of IgM and also play a role in signal transduction after Ag binding (by analogy with the TCR associated CD3 components in T lymphocytes). We have used mAb and polyclonal antibodies against an intracytoplasmic epitope on one of these polypeptides (previously identified in murine B cells as the product of the B cell specific mb 1 gene) to study the distribution of the IgM-associated dimer in human cells. By immunocytochemical staining of normal and neoplastic B cells, we show that the human mb-1 protein appears early in B cell differentiation, probably before expression of cytoplasmic mu-chain, and persists until the plasma cell stage, where it is seen as an intracytoplasmic component. According to immunohistologic analysis of reactive lymphoid tissue and lymphoma samples, mb-1 protein is completely B cell specific. Anti-mb-1 also labels B cell areas in tissues from seven different mammalian species. Finally, the Ig-associated dimer could be isolated from human hairy-cell leukemia cells in high purity and yield by affinity chromatography using anti-mb-1 antibody. Mice immunized with this material have produced a strong polyclonal response, so that it should now be possible to prepare a panel of new mAb reactive with different epitopes on both mb-1 and on its associated polypeptide(s). PMID- 1747163 TI - Work stress after smoking cessation. AB - 1. Since smoking relapse occurs most frequently during the first 3 to 6 months after cessation, worksite maintenance sessions during this critical time may promote long term abstinence. 2. Uncertainty or ambiguity about what is expected of the worker on the job is a consistent predictor of relapse during the first year postcessation. 3. A worker's perception of workload is related to smoking status. Workers who perceived a heavier load at 3, 6, and 12 months postcessation were likely to have resumed smoking. PMID- 1747164 TI - Self-Efficacy Theory. Implications for the occupational health nurse. AB - 1. Self-efficacy, a concept derived from Social Learning Theory, provides a theoretical framework for behavior change. This framework can be used by the occupational health nurse to develop programs designed to effect behavior change. 2. Research studies focusing on behavior change (e.g., smoking cessation, weight control, exercise and cardiac rehabilitation, work resumption) employing the concept of self-efficacy are reviewed. 3. Self-efficacy predicts modification and maintenance of behavior. PMID- 1747165 TI - Shiftwork. Consequences and considerations. AB - 1. The shiftworker's inability to adapt to shiftwork schedules can lead to a loss of physical and psychological well being, and can produce negative safety and performance consequences. 2. The factors that contribute to the intolerance of working shiftwork schedules are complex and interrelated and include host variables (i.e., circadian rhythms) and environmental variables (i.e., type of shifts worked). 3. The most direct and consistent effect of working shiftwork is the impairment of the quality and quantity of sleep. 4. Interventions should include a program that monitors workers' tolerance to shiftwork and provides information and recommendations for employees to effectively manage a lifestyle that incorporates nighttime work schedules. PMID- 1747166 TI - Occupational stress and burnout in the nursing profession. A model for prevention. AB - 1. Work overload, lack of control over one's work, non-supportive work environment, limited job opportunity, role ambiguity, rotating shift work, and machine paced work are occupational stressors that have been suggested as factors contributing to psychological disorders. 2. The model of occupational stress defined in this article utilizes organizational social support and coping strategies as buffering agents with the potential to decrease occupational stress and burnout. 3. Although this model and suggested methods for measurement of components in the model were developed for the investigation of stress in health care populations, the model can be applied to other work settings. PMID- 1747167 TI - Carpal tunnel syndrome among employees at a window hardware manufacturing plant. Health hazard evaluation series. PMID- 1747168 TI - Strategies to develop "interconnectedness". Part I: Connections within the organization. PMID- 1747169 TI - Forty years of litigation involving residents and their training: I. General programmatic issues. AB - An analysis of reported state and federal adjudication from 1950 through 1989 was undertaken to identify issues and trends in litigation involving residents and their training. Of the 174 decisions cited, 38 (22%) involved disputes over general programmatic issues. The great majority of these addressed academic administration, especially issues arising from dismissals of residents. During more recent periods, residency programs have accommodated to judicial scrutiny of dismissals and have prevailed more often than claimants in litigation. Successful accommodation by residency programs has apparently not operated as a disincentive to further litigation, however. PMID- 1747170 TI - Involvement of health maintenance organizations in graduate medical education. AB - Prepaid health care plans are likely to play an important part in the current transition from inpatient to ambulatory care training of physicians, because such plans enroll one in seven Americans. In the spring of 1990, the Group Health Association of America conducted a survey of health maintenance organizations (HMOs) to assess their level of involvement in graduate medical education (GME). A questionnaire was sent to the 481 HMOs in the United States that had been operational for at least four years; 58% responded. Fifteen percent (42 HMOs) indicated that they were directly involved in GME. The majority of these 42 indicated that they had an agreement with an academic medical center (AMC) or a teaching hospital to serve as an ambulatory care rotation site. About one-sixth of the 42 HMOs had been approved by the Accreditation Council for Graduate Medical Education to serve as a sponsoring organization. HMOs directly involved in GME were more likely to be staff model and group model HMOs; older plans with an enrollment of 50,000 or more; not-for-profit plans; and those owned or sponsored by an AMC. PMID- 1747171 TI - The potential of the academic medical center to shape policy-oriented rural health research. AB - Rural communities continue to have problems in gaining access to basic health care services, a problem exacerbated by persistent shortages of physicians, financially threatened rural hospitals, and weak local economies. Academic health centers can help to address these issues, not only by increasing the flow of their graduates to rural areas, but also by supporting health services research designed to shape public policy that affects the rural United States. Examples of such research include experiments designed to influence the locational decisions of medical students and residents, studies of the quality and cost-effectiveness of care in rural hospitals, and the testing of new ways to provide emergency medical care in rural areas. Such policy-oriented research is compatible with both the intellectual and the service missions of most medical schools; in addition, lessons learned in rural areas may be relevant in more urbanized areas. PMID- 1747172 TI - An elective course in medical history. PMID- 1747173 TI - The fee schedule and academic medicine. PMID- 1747174 TI - The Veterans Health Administration: a health care model for the nation. PMID- 1747175 TI - Credit and responsibility in authorship. PMID- 1747176 TI - Affirmative action for women and promotion of academic excellence. PMID- 1747177 TI - Physicians as human engineers. PMID- 1747178 TI - A student-organized nutrition course. PMID- 1747179 TI - Teacher definition. PMID- 1747180 TI - Where physicians practicing in Appalachia in 1978 to 1990 were trained and how they were distributed in urban and rural Appalachia. AB - Medical school graduates who graduated from 1978 to 1986 were analyzed to determine the health professions' ability worldwide to educate and place primary care physicians in rural areas of Appalachia. These data indicate that the University System of West Virginia--consisting of the West Virginia School of Osteopathic Medicine, West Virginia University Medical School, and Marshall University Medical School--produced the most primary care physicians who began practicing in rural Appalachia during the 1980s. The West Virginia School of Osteopathic Medicine successfully retained 106 (26%) of its graduates in primary care practices throughout rural Appalachia, with 77 of them in rural West Virginia, making the institution the nation's leading provider of primary care physicians practicing in rural Appalachia and West Virginia during this eight year study period. With the exception of West Virginia, these and additional data support concerns of medical educators and public health officials that physicians in Appalachia are distributed disproportionately, more to urban than to rural counties. PMID- 1747181 TI - A review of studies concerning effects of sleep deprivation and fatigue on residents' performance. AB - Possible effects of sleep deprivation and fatigue on the performance and well being of residents have received little scientific examination until recently. This article is a review of the studies on this topic published since 1970. All those studies that dealt with residents' moods and attitudes demonstrated deleterious effects of sleep deprivation and fatigue. The implications of this finding for patient care deserve exploration. Residents' acuity on performance tests requiring prolonged vigilance tended to deteriorate with acute sleep loss, while their performances on most brief psychomotor tests measuring manual dexterity, reaction times, and short-term recall were not adversely affected. The data presently available suggest that sleep-deprived or fatigued house officers can compensate for sleep loss in crises or other novel situations. However, sleep deprived residents may be more prone to errors on routine, repetitive tasks and tasks that require sustained vigilance, which form a substantial portion of residents' workload. The authors concur with the recommendation of the Executive Council of the Association of American Medical Colleges that the total working hours for residents should not exceed 80 hours per week averaged over four weeks. PMID- 1747182 TI - Impact of physicians' part-time status on inpatients' use of medical care and their satisfaction with physicians in an academic group practice. AB - Inpatients' use of medical care and their satisfaction with their physicians were examined comparing the patients of three part-time physicians and five full-time physicians in an internal medicine group practice at the Columbia-Presbyterian Medical Center. In one study, by chart review over a seven-month period in 1988, each patient's length of stay and severity of illness were measured. A total of 58 cases were reviewed: 34 from full-time physicians and 24 from part-time physicians. When matched for severity of illness, there was no difference in lengths of stay between the patients of the part-time and those of the full-time physicians. In a second study, on interviewer-administered questionnaires completed over a ten-month period in 1986-1987, 60 patients gave satisfaction ratings of their primary physicians: 36 with full-time physicians and 24 with part-time physicians. Patients' satisfaction was equally high for both groups of physicians. The authors suggest that since more women physicians in internal medicine are demanding part-time work, and since part-time arrangements have been criticized as having adverse effects on patient care, their findings may contribute to more enlightened attitudes towards physicians who choose part-time status. PMID- 1747183 TI - Residency directors' assessments of which selection criteria best predict the performances of foreign-born foreign medical graduates during internal medicine residencies. AB - In the summer of 1990, 102 directors of internal medicine residency programs from nine areas of the country with the largest numbers of foreign-born foreign medical graduates (FFMGs) were surveyed by mail to determine what criteria used to select FFMGs for residency positions best predicted performance. The directors felt that the most important predictors were performance on the Foreign Medical Graduate Examination in the Medical Sciences or the National Board of Medical Examiners examinations; performance during the interview; and postgraduate clinical experience in the United States. Recent graduation from medical school was felt to be a better predictor than postgraduate clinical experience in a foreign country. Seventy-three percent of the directors found letters of recommendation from a foreign country to be useless. The author suggests the results of this study may be useful to residency programs in evaluating FFMG applicants and to FFMGs in assessing their own credentials. PMID- 1747184 TI - Association between third-year medical students' abilities to organize hypotheses about patients' problems and to order appropriate diagnostic tests. AB - The authors studied the abilities of three groups of third-year medical students (a total of 310) at two schools to order appropriate diagnostic tests and procedures for four cases studies. Each student was classified as "organized," "mixed," or "non-organized" based on the degree of organization of the approach the student used to list hypotheses for the two cases he or she was assigned. Analysis of variance revealed that the students in the organized and mixed groups spent significantly fewer dollars for inappropriate diagnostic evaluations than did the students in the non-organized group for three of the four cases (p less than .05). Analyses of the mean expenditures for all cases revealed that the students in the organized and mixed groups spent significantly fewer dollars for inappropriate evaluations than did the students in the non-organized group (p less than .05). The medical school that was teaching its students to organize hypotheses had more students in the organized group than expected for every case. The authors conclude that the ability of students to organize hypotheses is directly related to their ability to avoid increased expenditures for inappropriate diagnostic tests and procedures, and that organized thinking about patients' problems is a skill that can be taught. PMID- 1747185 TI - Internal medicine residents' monitoring of their colleagues' moonlighting activities at the University of Cincinnati. AB - The University of Cincinnati Department of Internal Medicine instituted in 1989 90 a peer review moonlighting committee of residents to (1) design departmental guidelines for work activities and number of work hours, (2) confidentially document work activities of fellow residents, (3) identify discrepancies between the recommended guidelines and residents' work activities, and (4) initiate control policies. Quarterly self-report questionnaires documenting moonlighting activities were given to each of the 35 residents in the second and third postgraduate years (20 and 15 residents, respectively). There was a 98% compliance rate by the residents through the initial 12 consecutive months. The completed questionnaires indicated that there were four first-time violators of established guidelines. The authors suggest that a peer review moonlighting committee may help in establishing mutually acceptable work activity guidelines while maintaining the accountability of the residency review committee and the program director. PMID- 1747186 TI - Estimating impacts on developing countries of the decrease in U.S. training opportunities for foreign medical graduates. AB - Between 1973 and 1983, the number of foreign nationals from developing nations who entered the United States for graduate medical education decreased by approximately 90%. Many of those who would have studied in the United States if this decrease had not occurred would have returned home to serve their countries. To estimate the impact of this loss, a survey was conducted in six major cities in Latin America between 1983 and 1989. Selected local medical students interviewed 554 physicians who had returned home after U.S. training and 60 of their classmates who had not trained there. The findings indicate that the returned physicians had given approximately twice as much time to teaching, research, and medical administration as did those who had not left home. The authors maintain that this and related findings show how the curtailment of opportunities for training foreign nationals in the United States is detrimental to both the aspirations of developing nations and the influence of the United States in world affairs. PMID- 1747187 TI - Investigating whether timing of students' third-year internal medicine clerkships affects their performances as seniors on the NBME examination. PMID- 1747188 TI - Comparing the resource use of sympathetic and empathetic physicians. PMID- 1747189 TI - Computer simulations of electron-transfer reactions in solution and in photosynthetic reaction centers. PMID- 1747190 TI - New methods for electronic structure calculations on large molecules. PMID- 1747192 TI - Generation of high-resolution protein structures in solution from multidimensional NMR. PMID- 1747191 TI - Electrode reactions of well-characterized adsorbed molecules. PMID- 1747193 TI - Vibrational energy relaxation and structural dynamics of heme proteins. PMID- 1747194 TI - Characterization of service intervals and frequency of short oestrus cycles in Zebu (Bos indicus) cows in Ethiopia. AB - Data collected over a 10-yr period on 1,778 service intervals in 1,111 Arsi (Bos indicus), cows at the Ethiopian Ministry of Agriculture ranch were analyzed. Conception rate to first service was 48%, cows calving from June to February being more likely to conceive at first oestrus. Overall interval between services in animals returning for insemination averaged 53 +/- 40 (SD), range 6-262 d. There were (6%) "short" cycles of less than 17 d, mostly during the first (69%) and second (30%) intervals (P less than 0.01). A quarter of service periods (24%) were within the normal length of 18-24 d, 52% were its multiples while 18% were abnormal and probably indicative of embryonic mortality. First oestrus cycle length was affected by year (P less than 0.01) and season of calving (P less than 0.05). Second oestrus cycle length was influenced by season of calving and first oestrus onset (P less than 0.05). It is concluded that the low frequency of normal cycles is to a large extent due to heats which remained undetected by visual observation in Arsi cows under artificial insemination programmes. PMID- 1747195 TI - Ca2+ as a messenger of dorsal--ventral polarity formation in frog (Rana temporaria) eggs. AB - Three methods of Ca2+ administration were used to influence the location of the grey crescent and the dorsal lip of blastopore in R temporaria eggs, ie a Ca2+ microinjection into the subcortical cytoplasm, egg pricking in high Ca2+ solutions and Ca2+ ionophore A23187 microinjection and application. The treatments all induced grey crescent and dorsal lip of blastopore formation near the Ca2+ administration site. Inositol trisphosphate injections gave similar results. Colchicine injections into the eggs inhibited the appearance of both natural and Ca(2+)-induced grey crescents. PMID- 1747196 TI - [Refeeding after ingestion of diets containing 10% soybean protein associated with various concentrations of alginate or sodium carrageenan. Effects on growth and lipid parameters in the rat]. AB - Male 21-d-old Wistar rats were fed over 3 experimental periods. During the first period of 4 wk, diets contained 10% casein or defatted soy flour proteins, with or without 0.5, 1, 2 or 3% sodium alginate or sodium carrageenan, and were heated. During the second period, they were fed a standard diet for 16 wk with 17% proteins, and during the third period, they received the same diet as in the first period, but with 20% proteins. Rat body weights were measured throughout the study period; plasma lipid levels were then determined after fasting. Presence of sodium alginate in the diet had no effect on growth, but rats fed carrageenan presented growth retardation at the end of the experimental period, which was not altered by refeeding the standard diet. Sodium alginate did not modify rat triglyceridemia, except at the 1% level. Carrageenan had a hypotriglyceridemic effect. Alginate and carrageenan had no effect on blood cholesterol. Compared to soybean protein, casein intake did not increase plasma cholesterol levels as generally described. The effect of carrageenans on growth and plasma triglyceride levels could be a result of their physico-chemical properties. PMID- 1747197 TI - Insulin and glucose in neonatal calves after peroral insulin and intravenous glucose administration. AB - Effects of peroral insulin on plasma concentrations of immunoreactive insulin (IRI) and glucose in newborn calves were studied. Bovine insulin was administered in amounts of 0.5 mg/kg body weight immediately preceding first colostrum. Thereafter, neither an increased IRI response nor a lowering of blood glucose level were observed, indicating that insulin was either not absorbed from the intestine or possibly retained in the liver. Feeding of whole milk was followed by a higher rise in IRI and glucose concentrations than feeding of colostrum after po insulin. However, when compared with 1-3-month old calves, IRI responses to feeding and to iv infused glucose were markedly smaller on the first and second day of life respectively, while glucose responses were similar. This indicates that insulin secretory mechanisms are not fully developed in the newborn calf. PMID- 1747198 TI - [Transport of amino acids in the splanchnic bed by blood plasma and blood in the preruminant calf]. AB - Three preruminant calves were fitted with catheters in portal and hepatic veins and in a mesenteric artery. Two electromagnetic flowmeter probes were clipped around the portal vein and the hepatic artery. The calves were fed either a diet with a low (L) or a high (R) abomasal emptying rate for dietary proteins. Blood flow and free amino acid levels in plasma (P) and blood (S) were determined before the morning meal and during the following 7 h. In the portal vein, for most amino acids P/S ratios were correlated to the net amino acid balance of the digestive tract measured in plasma. By contrast in the hepatic vein, these ratios were mainly correlated to hepatic balance measured in whole blood. Correlations between digestive tract and hepatic balance calculated using either plasma or whole blood pool were different for some amino acids. This suggests that amino acid exchange between plasma and blood cells is low and absorbed amino acids are mainly transported to the liver by plasma, whereas whole blood rather than plasma is concerned in amino acid exchanges in the liver. PMID- 1747199 TI - Intestinal absorption of calcium from yogurt in lactase-deficient subjects. AB - Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency. PMID- 1747200 TI - Relationships between plasma lipoproteins and glucose in fasted chickens selected for leanness or fatness by three criteria. AB - In order to identify the mechanisms which underlie fattening in commercial birds, lean and fat broiler chickens have been selected according to 3 different criteria: abdominal fat content, plasma glucose level and plasma concentration of very-low-density lipoproteins (VLDL), the latter being the main substrate from which bird adipose tissues accumulate triglycerides. Chickens selected for high abdominal fat content displayed a higher level of VLDL and a lower level of glucose than their lean counterparts. Conversely, selection for high plasma VLDL or low plasma glucose resulted in 2 fat lines of chickens. The differences in intermediate- and low-density lipoproteins reflected a different balance in synthesis and catabolism of VLDL among the lines, whereas there was no difference in high-density lipoproteins. These data clearly demonstrate the relationship between lipid and carbohydrate metabolism and their role in the susceptibility to fattening. They suggest a greater use of carbohydrate for hepatic lipogenesis in fat chickens, resulting in a higher synthesis and secretion of VLDL and of their subsequent accumulation of triglycerides in the adipose tissue. PMID- 1747201 TI - Thyrotropin-releasing hormone (TRH) is not thyrotropic but somatotropic in fed and starved adult chickens. AB - Adult fed and starved Warren chickens, 2 yr of age, and approaching the end of the second laying year, were injected iv with 1 of the following products: 10 micrograms of thyrotropin releasing hormone (TRH); 100 micrograms of bovine thyrotropin (bTSH); 100 micrograms of ovine growth hormone (oGH); saline. The influence on plasma concentrations of thyroxine (T4), triiodothyronine (T3) or chicken GH (cGH) were followed. Prior to injection, it was clear from the control values that starvation for 3 d decreased plasma levels of T3 and increased cGH, whereas 7 d of fasting increased T4 and cGH. The plasma levels of cGH were elevated greater than 10-fold at 15 min following the TRH challenge in food deprived chickens compared to a less than 4-fold increase in normal fed hens. This increase was followed by a rise in T3 after 1 h, which was also more pronounced in the starved animals, whereas T4 decreased or remained unaffected. Increases in T4 can, however, be obtained with 100 micrograms TSH in normal fed (2-fold) or starved animals (greater than 3-fold). Following injection of 100 micrograms oGH, a significant increase in T3 levels was observed which in fed animals was already present at 30 min, but the higher levels persisted for 1 and 2 h in fed and starved hens. At the same time, a decrease in T4 was observed in both groups of GH-treated chickens. It is concluded that TRH at the dose used is not thyrotropic but has a somatotropic effect and is responsible for the peripheral conversion of T4 into T3. PMID- 1747202 TI - Microscopic investigation of changes in histology and digestibility in the rumen of a forage grass and a forage legume during the first growth stage. AB - An Italian "Dalita" ryegrass (Lolium italicum) and a European lucerne (Medicago sativa) were harvested at 5 different growth stages to determine the anatomical factors limiting their digestibility and in particular the effects of lignification of the tissues. In vitro digestibility, cell wall contents of the whole plant and stem of lucerne and of the whole plant, stem and leaf blade of ryegrass were determined. The rate and the extent of degradation in the rumen of the different tissues were observed by scanning electron microscopy. This degradation occurred very rapidly with the lucerne stems; the xylem of lucerne was the only undegradable tissue whatever the stage. The collenchyma was degraded in the rumen although with acid phloroglucinol it stained positive for the presence of phenolic compounds. Ryegrass stems were digested more slowly than lucerne stems, and the sclerenchyma and xylem of ryegrass were indigestible whatever the stage. The parenchyma located close to the sclerenchyma became indigestible as the cell walls lignified progressively from the third stage. These results contribute to the understanding of the decrease in digestibility over the first growth stage and the variation in rate of digestion of lucerne and ryegrass in the rumen. PMID- 1747203 TI - Differential effects of T4 and T3 on TRH- and GRF-induced GH secretion in the domestic fowl. AB - The in vivo growth hormone (GH) response of immature domestic fowl to thyrotrophin-releasing hormone (TRH) and GH-releasing factor (GRF) was suppressed in birds fed diets supplemented (1 ppm) with triiodothyronine (T3) or given bolus intraperitoneal (ip) injections (100 micrograms/kg for 10 d) of T3. Supplementation (ppm) of the diet with T4 had no effect on secretagogue- induced GH release. Exogenous T3 or T4 suppressed basal, TRH- and GRF-induced GH release 2 h after daily ip administration (100 micrograms/kg for 10 d). 24 h after the last injection, only T3 was effective in inhibiting basal and stimulated GH secretion in vivo. The systemic administration of T3 was followed 2 h and 24 h later by a downregulation of pituitary TRH binding sites. T4 administration had no effect on pituitary TRH binding. When chicken pituitary glands were incubated in vitro, basal GH release was unaffected by the addition of 10(-9)-10(-5) M T3 or T4 to the incubation media. The in vitro GH response to TRH (10(-6) M) or GRF (10(-6) M) challenge was, however, suppressed in a dose-related manner by T3 but was unaffected by the coincubation of T4. These results demonstrate inhibitory effects of T3 and T4 on basal and secretagogue-induced GH secretion in fowl. T4 is less active than T3 and probably exerts some of its effects via T3-independent mechanisms. PMID- 1747204 TI - Light- and electron-microscopic observations on the relationship between prelampbrush oocytes and surrounding granulosa cells in the laying Japanese quail (Coturnix coturnix japonica). AB - Transmission electronmicroscopic (TEM) observations demonstrated that the most superficial region of quail oocytes during the prelampbrush stage differs locally from the deeper ooplasm and is an active zone which forms exooplasmic cones, ridges or knob-like protrusions in the direction of/or in the granulosa cells. This exooplasm, in which no mitochondria were seen, is separated from the endooplasm, by a narrow interrupted filamentous layer. Using a lipid-preserving method of fixation, morphological evidence was found for the transport of lipid material from the granulosa cells into the exooplasm of the oocyte. Open intercellular bridges between exooplasm and granulosa cell cytoplasm were also seen. Differences between the electronmicroscopic aspect of clear and dark granulosa cells have been described. PMID- 1747205 TI - First reflection: a special transcultural experience. PMID- 1747206 TI - Transcultural nursing: providing culturally congruent care to the Hausa of Northwest Africa. AB - Research around the world is now beginning to validate the theory of Cultural Care as an important means to provide culturally congruent care to clients, families, and groups of diverse cultures. Knowledge of Leininger's Theory of Cultural Care Diversity and Universality can provide meaningful care to clients who have different traditional and current beliefs and values. The Leininger Sunrise Model can serve as a valuable guide to discover care meanings and practices related to the theory, and to provide practical and meaningful culture specific care decisions and actions by nurses. The three major modes of action, namely, cultural care maintenance or preservation, accommodation or negotiation, and repatterning or restructuring, are important differential means to provide culturally congruent care to clients within their own cultural setting. This article considers the application of such care for the Hausa of Northwest Africa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747207 TI - Second reflection: comparative care as central to transcultural nursing. PMID- 1747208 TI - Transcultural care principles, human rights, and ethical considerations. AB - During the past three decades, the author has developed and used some general principles to guide transcultural instruction, practice and research. These principles were developed from my transcultural care theory, research studies and direct clinical experiences, consultation and general writings on the subject [Leininger 1967, 1970, 1973, 1976, 1978, 1979, 1980, 1981, 1984a, 1984b, 1988, 1989, 1990]. The principles include some assumptive premises with regard to universal and diverse considerations of human beings with the importance to know and respect the cultural rights of people in order to provide meaningful, satisfying and appropriate culture care to people. Through the years, a number of nursing students, faculty, and clinicians have used these principles, rights and ethical considerations to guide them in their thinking and to protect client's human and ethical rights. Since many nurses frequently request copies of these statements for teaching, consultation and clinical work, they are published below with this intent in mind. PMID- 1747209 TI - Response to published article: nursing diagnosis. PMID- 1747210 TI - Transcultural nursing in South Africa: prospects for the 1990's. PMID- 1747211 TI - Harmonizing: a North American Indian approach to management of middle ear disease with transcultural nursing implications. AB - In a grounded theory study of Canadian Indian family management of persistent middle ear disease, harmonizing was identified as the major strategy employed in the process of learning to manage. This finding resulted in a recasting of the substantive theory of management identified in an earlier study of Caucasian families. Although families from both cultures advance and retreat on the continuum of learning to manage in response to the relationship with the health care system, the effects of the disease on the child, and the amount of disruption in family life, culture was found to influence the ways in which these families learned to manage. In general, native families harmonized by integrating the experience into their reality in contrast with their Caucasian counterparts who attempted to direct or take charge of the experience. Factors that influenced native Indian management included autonomy of the child, perceptions of health and illness, expectations of the health care system, orientation to present and past time, and listening skills. These findings significantly contributed to the development of transcultural nursing knowledge. PMID- 1747212 TI - Variation in apparent serum digitalis-like factor levels with different digoxin antibodies. The "immunochemical fingerprint". AB - Increased levels of a circulating digoxin-like factor (DLF) occur in a number of physiologic states in which sodium homeostasis is altered, and may contribute to the pathogenesis of hypertension. We exploited the different affinities for DLF of seven antisera directed at digoxin to develop an immunochemical profile, and then employed this index to address two questions: does the same DLF species exist in several conditions associated with increased DLF levels, including pregnancy, renal failure, hepatic failure, and neonatal cord blood? Will this approach prove useful in assessing candidates proposed to be DLF? An identical profile was identified in serum from pregnant women and patients with renal or hepatic failure, and a highly significant correlation existed between DLF levels measured with antisera of high and intermediate affinity in 42 subjects with increased levels (r = 0.93; P less than .001). In patients with renal failure, when endogenous DLF levels were too low to assess the profile, concentration of the serum resulted in measurable DLF levels that had an identical profile. The profile was somewhat altered in umbilical cord blood, perhaps reflecting an influence of increased steroid hormone levels. Among agents suggested as candidates for DLF, neither lysophosphatidylcholine nor ouabain showed a profile resembling DLF. Progesterone, 17-OH-progesterone, and bufalin, on the other hand, did show substantial similarity, perhaps providing a clue to the structure of DLF. The normal plasma levels of progesterone and 17-OH-progesterone are 100- to 1000-fold too low to be candidates for DLF and bufalin was sufficiently dissimilar not to be a candidate. DLF in at least three different patient populations probably represents identical chemical species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747213 TI - Parathyroid hypertensive factor is present in DOCA-salt but not two-kidney-one clip hypertensive rats. AB - In order to determine whether the expression of parathyroid hypertensive factor (PHF) is secondary to hypertension or whether it is specifically related to low renin hypertension, PHF levels were measured in DOCA-salt and two-kidney-one-clip (2K-1C) hypertensive rats. Despite equivalent elevations of blood pressure, PHF was detected in the DOCA-salt rats, but not in the 2K-1C rats (17.5 +/- 3.1 mm Hg, P less than .0001 v 0.9 +/- 2.8 mm Hg, P = NS, respectively). Moreover, PHF levels correlated with mean arterial pressure in the DOCA-salt group (r = 0.91, P less than .0001). We conclude that PHF expression is not a secondary phenomenon caused by hypertension, but rather may be causally related to the development of low-renin forms of hypertension. PMID- 1747214 TI - Rapid smooth muscle cell growth and endogenous prostaglandin system in spontaneously hypertensive rats. AB - Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit rapid cell growth. In this study, to reveal the mechanisms of the quick VSMC growth, we analyzed the alterations in the respective periods of the proliferating cell cycle, and investigated the role of the endogenous prostaglandin system in this rapid cell growth. The VSMC from SHR showed increased [3H]thymidine uptake and shortened doubling time, compared with Wistar Kyoto rats (WKY). These properties were mainly due to both shortened transition time from G0/G1 to S and shortened G2 duration. There was a difference neither in the DNA-replication rate nor in the mitotic period. Generating capacity for vasodepressor prostaglandins was significantly reduced in the VSMC from SHR, particularly in the G0/G1 period. When the endogenous prostaglandin synthesis was inhibited by 10(-5) mol/L indomethacin, the transition from G0/G1 to S was shortened. This alteration was eliminated by supplementation with OP41483, a stable prostacyclin analog. In contrast, the alteration in the G2 duration was unaffected by indomethacin. These data indicate that the rapid VSMC growth in SHR is mainly due to the shortening of both the G0/G1 and G2 period, and that the impaired prostaglandin system is responsible, at least in part, for the shortened G0/G1 duration. PMID- 1747215 TI - Influence of sex and body weight on forearm hemodynamics in patients with sustained essential hypertension. AB - Forearm hemodynamics using pulsed Doppler flowmeter measurements were studied in 60 hemodynamics men (30 nonobese and 30 obese) and in 45 hypertensive women (15 nonobese and 30 obese subjects). Age and blood pressure of nonobese and obese patients were identical in men as well as in women. Blood flow, expressed in milliliters/minute or corrected for body surface area, was significantly higher in obese hypertensive patients. When blood flow was expressed per unit liter of forearm volume, the difference was no longer present. The increased blood flow in milliliters/minute in obese hypertensive patients was due to an increased blood velocity, while arterial diameter was similar in nonobese and obese hypertensive patients. Forearm vascular resistance, expressed either in absolute values or in normalized values was significantly higher in nonobese than in obese hypertensive patients. When men and women with similar body weight and mean arterial pressure were compared, women were characterized by lower values of arterial diameter, body surface area and forearm volume, whereas vascular resistance in absolute value or corrected for body surface area was higher. This increase was no longer present when vascular resistance was normalized for forearm volume. This study provides evidence that body composition and body mass index evolve as determinants of arterial blood velocity whereas the gender of the patient seems to influence the arterial diameter. PMID- 1747216 TI - Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril. AB - This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ. PMID- 1747217 TI - Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring. AB - We used 24-h monitoring of blood pressure (BP) to evaluate the effect of calcium supplementation on mild to moderate essential hypertension in elderly hospitalized patients for the first time in a controlled crossover study. The mean systolic and diastolic BP over a period of 24 h declined by 13.6 mm Hg (P less than .005) and 5.0 mm Hg (P less than .05) respectively in patients whose diet was supplemented with 1 g of elemental calcium in the form of oystershell electrolysate (AA calcium). Serum ionized calcium and urinary calcium and sodium excretion increased (serum Ca2+ 0.16 +/- 0.03 mEq/L, P less than .05; FECa 0.5 +/ 0.2%, P less than .05; FENa 0.4 +/- 0.1%, P less than .05) and plasma parathyroid hormone was suppressed (12.2 +/- 2.3 pg/mL, P less than .005). These data suggest that supplementation of dietary calcium may contribute to a reduction of BP in elderly patients with essential hypertension. PMID- 1747218 TI - Altered expression of inhibitory guanine nucleotide regulatory proteins (Gi alpha) in spontaneously hypertensive rats. AB - We have recently shown that the stimulatory effects of guanine nucleotides and some agonists on adenylate cyclase activity were diminished in aorta and heart sarcolemma (SL) of spontaneously hypertensive rats (SHR). In the present studies we have examined the activity of GTP-binding proteins (G-proteins) at ADP ribosylation level, by using pertussis toxin (PT) and cholera toxin (CT) at protein level, by using specific antibodies against Gi (inhibitory) and at mRNA level, by using cDNA probes encoding G-proteins. The labeling of Gi by PT was significantly increased in the aorta and heart SL from SHR as compared to their Wistar-Kyoto control rats (WKY). However, no change in the labeling of Gs (stimulatory) by CT was observed in SHR. Furthermore, immunoblotting experiments using AS/7 antibody which reacts with both Gi alpha-1 and showed an increased immunoprecipitation of Gi alpha-2 in heart SL from SHR. In addition, when the expression of G-proteins was probed at the mRNA levels by Northern blot analysis using cDNA probes, the mRNA levels of Gi2 alpha and Gi3 alpha were significantly enhanced in aorta and heart from SHR. However, the mRNA levels of Gs alpha were not altered in SHR. These results indicate that the gene of Gi and not of Gs is overexpressed in heart and aorta from SHR. PMID- 1747219 TI - White coat phenomenon in patients receiving antihypertensive therapy. AB - The occurrence of the white coat phenomenon in hypertensive patients receiving drug therapy was determined in a consecutive series of 71 patients undergoing ambulatory blood pressure (ABP) recordings because of suspected differences between office and ambulatory values. Overall mean (+/- SEM) office blood pressure (BP) was 166 +/- 2/95 +/- 1 v awake ABP 139 +/- 2/86 +/- 1 mm Hg. The white coat phenomenon [(office BP - ABP) greater than or equal to 20/10 mm Hg] was present in 52 of 71 patients: office BP 170 +/- 3/96 +/- 2 v ABP 135 +/- 2/83 +/- 1 mm Hg. A marked white coat effect [(office BP - ABP) greater than or equal to 40/20 mm Hg] was seen in 22 patients with office BP being 178 +/- 4/98 +/- 3 v ABP 131 +/- 3/79 +/- 2 mm Hg. The frequent occurrence of white coat phenomenon in these patients suggests that office BP readings may not always represent usual ABP in patients receiving chronic antihypertensive therapy. PMID- 1747220 TI - Verapamil and nifedipine in combination for the treatment of hypertrophy heart disease. PMID- 1747221 TI - Associated effect of hepatic hydroxymethylglutaryl coenzyme A reductase + angiotensin converting enzyme inhibitors on the progression of renal failure in hypertensive subjects. PMID- 1747222 TI - Proceedings of the 38th scientific session, Japanese College of Cardiology. Hiroshima, October 4-6, 1990. Abstracts. PMID- 1747223 TI - A recent advance in auricular reconstruction. PMID- 1747224 TI - Long-term survival after surgical resection for recurrent nasopharyngeal cancer after radiotherapy failure. AB - Results are reported of transpalatal, transcervical, and transmaxillary resection in 15 patients with recurrent nasopharyngeal cancer after failure of primary radiotherapy. Seven patients treated for cure have been followed up for more than 3 years (mean, 55 months; range, 40 to 82 months), with three (43%) remaining free of disease. Two patients are living with local disease (59 and 40 months postoperatively), while two have died of their local and regional recurrence (40 and 17 months postoperatively). Two additional patients underwent nasopharyngectomy for palliation. One of these patients died of uncontrolled disease 12 months postoperatively; the other remains alive with disease 70 months after resection. Six patients have been followed up for less than 3 years (mean, 22.3 months; range, 16 to 32 months). Of this group, one (17%) is without evidence of disease, four are living with local disease (13, 16, 17, and 27 months postoperatively), and one has died of disease (13 months postoperatively). Recurrence (10 of 13 patients) has occurred an average of 8 months after surgery (range, 4 to 17 months). Complications include transient marginal mandibular nerve weakness (one), permanent cranial nerve paralysis (two), nasopharyngitis and/or osteomyelitis of the cervical vertebrae or base of skull requiring intravenous antibiotics (two), aspiration pneumonia (two), prolonged nasogastric tube feeding (two), and intraoperative thyroid storm (one). No cerbrospinal fluid leaks or perioperative deaths occurred. The long-term cure rate and disease-free interval of transpalatal nasopharyngectomy lead us to believe that this technique is probably only slightly better than reirradiation in the appropriately selected patient. PMID- 1747225 TI - Parathyroid exploration. A review of 125 cases. AB - Cervical exploration was performed in 106 patients with primary hyperparathyroidism and in 19 patients with chronic renal failure. Initial exploration for primary hyperparathyroidism was successful in 97% of the cases. Single adenomas were found in 84, double adenomas in six, and multiple-gland hyperplasia in 12 patients. Two of the four patients in whom cervical exploration failed were ultimately given the diagnosis of benign familial hypocalciuric hypercalcemia. Thirteen adenomas were ectopic. Preoperative thallium-technetium scans and ultrasound correctly localized only 63% of the adenomas. Only 45% of the ectopic adenomas were correctly localized. All four glands should be examined at initial exploration. Because of the occurrence of double adenomas, contralateral exploration is always indicated regardless of whether an enlarged gland and a normal one are found on the first side. All enlarged parathyroids should be removed when dealing with single or multiple adenomas; subtotal parathyroidectomy (3 1/2 glands) should be performed in multiple-gland hyperplasia. Frozen section confirmation of excised parathyroid tissue is essential. If exploration is unsuccessful, ectopic locations such as the retroesophageal areas, thymus, anterior and posterior mediastinum, carotid sheath, and thyroid lobe must be searched carefully. Preoperative localization studies are not as reliable as an experience parathyroid surgeon. PMID- 1747226 TI - The combined latissimus dorsi-scapular free flap in head and neck reconstruction. AB - Microvascular free tissue transfer techniques offer great versatility in the selection of tissue for reconstruction of head and neck defects. The system of flaps based on the subscapular artery and vein provides the widest array of composite free flaps. The possible flaps that can be harvested based on this single vascular pedicle include the scapular and parascapular skin flaps, the serratus anterior and latissimus dorsi muscle flaps, and the lateral scapular bone flap. In addition, a segment of vascularized rib can be transferred with the serratus anterior and latissimus dorsi muscles. Large cutaneous defects can be resurfaced by combining the latissimus dorsi and scapular flaps. Another advantage of this combined flap is the independent vascular pedicles of its components, which allow freedom in orientation of the various tissue segments. Thus, the combined flap can be helpful in reconstructing complex three dimensional composite defects of the head and neck. In addition, by reinnervating the muscle portions of this flap, bulk can be preserved and an improved functional reconstruction of the oral cavity achieved. A review of the literature shows three previous reports utilizing this combination of flaps in five patients. We report the use of the combined latissimus dorsi-scapular free flap in six patients to reconstruct massive composite defects of the oral cavity, midface, and scalp. There was one flap failure, which was successfully reconstructed with the contralateral latissimus dorsi-scapular flap. The anatomy of this flap is reviewed, and the indications for its application are discussed. PMID- 1747227 TI - Prognostic variables in parotid gland cancer. AB - We performed a retrospective review of 178 previously untreated patients with primary malignant neoplasms of the parotid gland treated at our institution between 1960 and 1985. Patients were followed up for a median of 7.5 years. Fifty nine percent underwent surgery alone, and 40% underwent surgery and radiation therapy. Univariate and multivariate analyses established the prognostic influence of cancer stage, cancer grade, histologic type, presence of lymphatic invasion, perineural invasion, tumor size, extension beyond the parotid gland fascia, cervical adenopathy, quality of margins, and patient age and gender. Survival was influenced most by tumor grade, tumor size, presence of positive cervical lymph nodes, and facial nerve invasion. The risk of local-regional recurrence was most affected by cervical adenopathy and tumor size. Distant metastases were predicted by tumor grade and size. At last contact, 39% of patients were alive and free of disease, while 26% had died of the disease. We analyzed the optimal surgical procedure and the rationale for the selection of combined treatment. PMID- 1747228 TI - Elevated levels of soluble interleukin 2 receptor and tumor necrosis factor in nasopharyngeal carcinoma. AB - Depressed cell-mediated immunity as a measure of the mitogenic response of mononuclear cells in patients with nasopharyngeal carcinoma is well documented, but the mechanism is still unclear. The enzyme-linked immunosorbent assay was used to measure soluble interleukin 2 receptor and tumor necrosis factor levels in 295 patients with nasopharyngeal carcinoma and 97 age-matched control subjects. Soluble interleukin 2 receptor levels in patients with nasopharyngeal carcinoma were elevated and correlated with clinical staging. Higher soluble interleukin 2 receptor levels were found in patients with bone metastasis but not in patients with intracranial involvement. The levels of tumor necrosis factor in nasopharyngeal carcinoma were higher than in control subjects but did not correlate with clinical staging. These data suggest that soluble interleukin 2 receptor levels might be more useful than soluble tumor necrosis factor levels that indicate tumor bulk. Soluble interleukin 2 receptor serves as a blocking factor that competes with interleukin 2 function, resulting in a decreased mitogenic response in patients with nasopharyngeal carcinoma. The usefulness of the levels of soluble interleukin 2 receptor to monitor the efficacy of treatment in patients with nasopharyngeal carcinoma with bone metastasis requires further study. PMID- 1747229 TI - Sutureless vascular anastomosis with biocompatible heat-shrink tubing. AB - We have tested a new method of vascular repair using biocompatible, low temperature, heat-shrinkable tubing on canine carotid arteries. All of 16 canine carotid arteries were patent immediately after the anastomosis. None of the anastomoses leaked after the clamps were released. Average time from severing the vessel to releasing the clamps was 12 minutes. At 2 weeks, nine of 12 vessels were patent; the three failures were attributed to infection of a seroma that occurred in all of the dogs' necks. Histologic evaluation of the uninfected cases showed no inflammatory exudate around the prosthesis. Macroscopic and electron microscopic examination confirmed healing of the endothelium across the anastomoses. Sutureless vascular anastomosis with biocompatible heat-shrink tubing is a potential new modality for the acute repair of severed vessels. PMID- 1747230 TI - The effect of postoperative radiation therapy on pharyngoesophageal reconstruction with free jejunal interposition. AB - Free tissue transfer of a jejunal segment was undertaken for laryngopharyngoesophageal reconstruction in 20 patients who received postoperative irradiation therapy. Treatment consisted of 1.8- to 2-Gy-fractions, the average total dose was 55.57 Gy (range, 40 to 66 Gy). Anastomotic strictures (six) were encountered early in the series and associated with stapled anastomoses. Hand-sewing the jejunoesophagostomy eliminated the problem. Enteric cutaneous fistula, bowel necrosis, and hemorrhagic enteritis were not observed. We conclude that the application of postoperative irradiation therapy to patients requiring jejunal interposition grafts is feasible. PMID- 1747231 TI - The effect of hyperbaric oxygen on growth of human squamous cell carcinoma xenografts. AB - Hyperbaric oxygen is an important adjunct to the treatment of patients with head and neck cancer with existing or recurrent wound healing problems. Anecdotal clinical observations and a recent study of chemically induced oral cancer in hamsters have raised concern that hyperbaric oxygen therapy may accelerate tumor growth in such patients. This study evaluated the effect of hyperbaric oxygen therapy on the growth of human squamous cell carcinoma xenografts in a proved animal model. Fresh tumor specimens from three patients with head and neck squamous cell carcinoma of varying degrees of differentiation were first subcutaneously transplanted into a nude mouse host. Growing xenografts were then transplanted into one of three mouse groups. Half of the mice in each group were given hyperbaric oxygen therapy. The transplant volume as an index of tumor growth was measured in controls and mice given hyperbaric oxygen therapy six times during the 3-week course. Xenograft growth was almost linear in all mice. No statistical difference in overall group mean growth rates was observed in mice given hyperbaric oxygen or control mice regardless of the degree of tumor differentiation. Xenograft tissue from all mice was microscopically examined for tumor mitotic indices and degree of differentiation. This study suggests that hyperbaric oxygen therapy has no effect on established tumor xenograft growth. PMID- 1747232 TI - Long-term problems in patients with tracheoesophageal puncture. AB - Two hundred forty-seven patients, followed up a mean of 18 months and up to 108 months, were retrospectively studied for problems related to or affecting tracheoesophageal puncture for voice restoration. Active cases, as well as those inactive and decreased, were included. There were 154 patients with primary and 93 with secondary tracheoesophageal puncture. Problems were encountered at least once in 137 cases (55%). The 20 types of problems identified occurred in frequencies ranging from 0.4% to 21%. Most difficulties developed within the first 6 months and in general were easily managed. However, problems such as recalcitrant leakage, difficulty with changing the prosthesis, and dislodgment of the prosthesis led to permanent tracheoesophageal puncture tract closure in 18 patients (7%). PMID- 1747233 TI - Intrathecal narcotics for relief of pain from head and neck cancer. AB - We describe our experience with nine patients with head and neck pain of malignant origin who were treated with continuous low-dose intrathecal morphine via a lumbar catheter and implantable subcutaneous drug delivery pump. All patients had failed prior attempts at oral narcotic pain control due to either poor pain control or intolerable side effects. Using a visual analogue scale where the most severe pain is rated as 10 and no pain is rated as 0, the mean visual analogue scale was reduced from 7.6/10 (range, 5 to 10/10) before implantation to 1.9/10, 2.0/10, and 0.5/10 at 1 week, 1 month, and 2 months after implantation, respectively. Complications were acceptable. We conclude that intrathecal administration of morphine is a safe and effective means of pain control. This method deserves serious consideration in patients with intractable pain secondary to head and neck malignancy. PMID- 1747234 TI - Intracellular calcium changes associated with in vitro lymphokine-activated killer and natural killer cell cytotoxicity. AB - Interleukin 2-activated peripheral blood lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to lyse tumor cells in a nonspecific fashion. Although the mechanisms involved in this cell-mediated lysis are unknown, previous work has shown that T-lymphocyte-mediated cytolysis is associated with massive fluctuations in the intracellular calcium concentration within target cells. Studies were undertaken to determine whether intracellular calcium concentration changes were associated with LAK-mediated cytotoxicity and to determine the effects of calcium channel blockade on in vitro cell-mediated cytotoxicity. Natural killer (NK) and LAK cell cytotoxicity in vitro were measured against head and neck squamous cell carcinoma (UMSCC-11a and UMSCC-38) and Daudi cell lines. Assays were performed in parallel with flow cytometry to measure changes in intracellular calcium concentration within the target cells. Compared with NK cells, LAK cells showed enhanced cytotoxicity against the UMSCC 11a and Daudi lines but not the UMSCC-38 cell line. Both NK and LAK cell cytotoxicity against all the target cell lines directly paralleled significant increases in calcium concentration in the target cells. The addition of verapamil hydrochloride inhibited the rise in intracellular calcium concentration in the sensitive target cells and significantly inhibited both NK and LAK cell cytotoxicity in all the cell lines. The NK cell activity was more sensitive than LAK cell activity to verapamil inhibition. These data suggest that changes in the target cell calcium concentration are early and important events in both NK and LAK cell cytotoxicity in vitro. PMID- 1747235 TI - Detection of squamous cell carcinoma xenografts in nude mice by radiolabeled monoclonal antibody E48. AB - We recently produced the monoclonal antibody E48 as a specific reagent for squamous cell carcinomas. In our ongoing investigations to use E48 for clinical tumor detection and therapy, fundamental aspects of the antigen have to be elucidated and practical applications of the antibody have to be tested in a preclinical model. Immunoelectron-microscopic studies localized the E48 antigen along the cell surface and in between desmosomes, suggesting that the antigen serves as an adhesion molecule. To evaluate the usefulness of E48 for radioimmunodetection of neck node metastases, nodes from 20 neck dissection specimens were tested. A strong reactivity was observed. Furthermore, F(ab')2 fragments of E48 were compared with the complete IgG E48 for selective tumor detection in an animal model. It was demonstrated that E48 F(ab')2 fragments localize faster and reach higher tumor-nontumor ratios than the whole molecule. PMID- 1747236 TI - Effect on cochlear potentials of lateral semicircular canal destruction. AB - Recording of the cochlear potentials was successfully performed during experimental labyrinthectomy in the guinea pig and in three patients with acoustic neuromas during translabyrinthine removal of the tumors. In the guinea pig, complete interruption of the duct of the lateral semicircular canal including the endolymphatic canal caused little change in the endocochlear DC potential of the first cochlear turn and input-output function curve of the N1 component of the compound action potential elicited by 8-kHz tone bursts. Further drilling of the vestibular labyrinth in the guinea pig caused decline of these potentials when the vestibular was opened. In patients with acoustic neuromas, the interruption of the duct of the lateral semicircular canal hardly altered the N1 input-output function curve and N1 input-latency function curve during the 1 hour observation period. Consistent preservation of cochlear function even after interruption of lateral semicircular canals suggests the possibility of partial surgical labryrinthectomy with preservation of hearing for lesions involving semicircular canals. PMID- 1747237 TI - HLA frequency in patients with recurrent acute otitis media. AB - Clinical data suggest the involvement of hereditary factors in children susceptible to recurrent acute otitis media. That relationships of varying degree exist between the frequencies of certain HLA antigens and various disease entities is well established. In the present study, we investigated the frequencies of a number of HLA antigens in 45 patients with clinical recurrent acute otitis media and compared these frequencies with those in a control group from the same district. The HLA-A2 antigen occurred in 80% (36/45) of the group with recurrent acute otitis media, as compared with 56% of controls. Of a subgroup of 11 children with recurrent acute otitis media who were prospectively followed up, 10 (91%) were HLA-A2 positive. The HLA-A3 antigen occurred in only 11% (5/45) of the group with recurrent acute otitis media as a whole (n = 45) in comparison with 28% of controls. Among 22 prospectively followed up children without any episode of acute otitis media during the first 3 years of life, the frequency of HLA-A2 was 45% (10/22) and that of HLA-A3, 32% (7/22). The results indicate the existence of a relationship between recurrent acute otitis media and the HLA-A locus, suggesting the involvement of genetic factors in the disease. PMID- 1747238 TI - Protracted Lhermitte's sign following head and neck irradiation. AB - Lhermitte's sign is a rare complication of head and neck irradiation involving the delivery of dose to the cervical spinal cord. Although uncommon, symptoms of lightning-like electric sensations spreading into both arms, down the dorsal spine, and into both legs on neck flexion following head and neck irradiation, causes great concern in both the patient and the physician. This spontaneously reversible phenomenon is important for the otolaryngologist and radiation oncologist to recognize and discuss. A particularly severe and protracted case of Lhermitte's sign involving a patient recently completing a radical course of radiation for nasopharyngeal carcinoma is described in detail, including a review of the literature surrounding the cause and management of this condition. PMID- 1747239 TI - Anterior ischemic optic neuropathy causing blindness in the head and neck surgery patient. AB - Anterior ischemic optic neuropathy is an uncommon and devastating event that can result in unilateral or bilateral blindness. It has been reported as a complication of ophthalmologic or general surgical and cardiothoracic procedures as well as a spontaneous event in severe systemic disease. Aggravating intraoperative factors include anemia, hemorrhage, hypotension, preexisting small vessel disease, and increased intraocular pressure. We present a case of anterior ischemic optic neuropathy as a complication in a 48-year-old man undergoing extensive resection of recurrent carcinoma of the head and neck. Possible contributing risk factors in our patient include preexisting hypertension, intraoperative blood loss, previous radical neck dissection with venous compromise, intraoperative head and neck edema, and the use of tightly adherent plastic bubble-type intraoperative eye protection. The possible pathogenesis of this devastating complication and recommendations for prevention and management of anterior ischemic optic neuropathy are described. PMID- 1747240 TI - Corticosteroid treatment of otitis media with effusion. PMID- 1747241 TI - Treatment of facial paralysis. PMID- 1747242 TI - A physical study of vibrating membranes in developing a middle ear prosthesis. AB - We present a prosthesis meant to replace the tympano-ossicular set as well as the measuring apparatus for developing and characterizing this prosthesis. Such biocompatible materials as silicone elastomer and Teflon are used. Effects due to aging and sterilization have been negligible. Comparisons with anatomic specimens have yielded good results. Furthermore, the first clinical trials with this prosthesis have been promising. PMID- 1747243 TI - Laryngeal configuration of 99 dysphonic patients. AB - The aim of this investigation was to study a wide range of dysphonic patients and determine the best matches among the laryngeal configurations on phonation for each patient and those previously established for control data, which were obtained from a professional voice user producing the whole range of voice qualities. Ninety-nine patients were selected and laryngeal photographs were produced for each patient. Fifteen laryngeal parameters were quantified and normalized. The data were sorted, scalar values assigned and a measure of similarity between configurations applied. The best, second-best, third-best and worst matches between each patient separately and the control data were then examined. Although 41% of the patients did not have particularly unusual configurations, 59% exhibited a narrowing of the laryngeal vestibule caused by epiglottic retraction, cuneiform fronting and/or false fold adduction. This suggests that clinical reports for patients with dysphonia should contain information not only on any lesions present but also on laryngeal configurations and, in particular, vestibular narrowing. PMID- 1747244 TI - Antidiuretic-hormone-induced morphological changes in the ampullary epithelium of the frog semicircular canal. AB - Morphological changes induced by in vitro treatment with arginine-vasotocin, the frog antidiuretic hormone, were studied in the ampullary epithelium of the frog semicircular canal. Morphological changes appeared only in the apical side of the dark cells, while the basal part of these cells and the other cells lining the semicircular canal did not show any change. Changes consisted of the appearance of numerous small vesicles in the apical cytoplasm and the development of microvilli on the apical plasma membrane of the dark cells. These results suggest that arginine-vasotocin could play a role in the regulation of endolymph section. PMID- 1747245 TI - Normal wound healing of the paranasal sinuses: clinical and experimental investigations. AB - Twenty-two patients underwent partial or complete ethmoidectomies and were subjected to standardized postoperative follow-ups including endoscopic photography of healing tissues. Sequential biopsies were also taken from the regenerating mucosa and compared with endoscopic findings. On this basis wound healing could be divided into four different phases, allowing for the diagnosis of healing disturbances and clinical planning of stage-dependent therapy. Additionally, a model of wound healing in the maxillary antrum of the rabbit was developed for better understanding the clinical observations. Regeneration of standardized mucosal defects was studied with three-dimensional histomorphological analysis. Circular wounds were found to regenerate concentrically, with wound closure starting by epithelial migration. Within 120 h, granulation tissue covering the wound surface started to become hyperplastic and bone apposition occurred with the formation of osteoid. The systemic application of prednisolone (2 mg/kg per day i.m.) and topical 5% dexpanthenol ointment resulted in an acceleration of late epithelial wound closure together with a reduction in hyperplastic granulation tissue. Local applications of "epidermal growth factor" had no significant effect. PMID- 1747246 TI - The reaction of the guinea pig cochlea to perforations of the round window membrane with and without perilymph aspiration. AB - The influence of simple opening of the round window (RW) membrane and the effect of aspiration of perilymph on the electrophysiological characteristics of the cochlea was tested in guinea pigs by measurement of the compound action potentials. We found that perforations of the RW membrane failed to lead to either short-term or long-term damage in cochlear function. There was only a slight spontaneous escape of perilymph but without measurable functional loss. Additional aspiration of perilymph led to entry of air into the basal turn and to an immediate loss of function of the cochlea. This regressed within 4 weeks in the middle- and low-frequency ranges. Measurable long-term damage persisted only in the high-frequency ranges. We attribute contradictory results of other authors to methodological errors which we avoided by a specific selection of healthy animals and the development of standardized operation, recording and measurement procedures. PMID- 1747247 TI - The surgical treatment of atelectatic ears and retraction pockets in children and adults. AB - Eighty-four ears which underwent tympanoplasty because of an atelectasis of the tympanic membrane were followed up. Thirty-six involved children (4-13 years old). On the average, 50-55 months of postoperative follow-up showed that atelectasis, once operated, shared the same pattern and prognosis in the children as in the adults. PMID- 1747248 TI - The value of fentanyl/diazepam anesthesia for experimental operations and recordings of compound action potentials in the guinea pig cochlea. AB - Fentanyl/diazepam anesthesia is an appropriate combination for surgical operations on the guinea pig, since it ensures definitive anesthesia and analgesia without respiratory depression. Comparative investigations with pentobarbital and urethane were carried out to check their applicability for electrocochleographic recordings. We found that fentanyl/diazepam combination anesthesia is more suitable for electrocochleographic investigations than pentobarbital. We were thereby able to prove that pentobarbital has an attenuating effect on electrocochleographic recordings in contrast to the findings reported in the available literature. For this reason, and because the lowest rates of animal morbidity occurred with fentanyl/diazepam, this combination anesthesia should be used preferentially for electrophysiological experiments in guinea pigs. PMID- 1747249 TI - A technique for quantitative cytology of nasal secretions. AB - To quantitatively analyze cellular elements in mucopurulent nasal secretions from patients with chronic paranasal sinusitis, we studied five mucus-liquefying agents--dithiothreitol (DTT), ethylenediaminetetraacetic acid tetrasodium salt, propylene glycol, serratio peptidase and urea--with Hanks' balanced salt solution used as a control. Agents were compared for the number of cells, the mucus liquefying effect and the staining characteristic of cells in cytocentrifuge prepared smears. The results indicated that the treatment of nasal secretions with 10 mM DTT provides more clear and detailed cytological preparations for quantitative cytology of nasal secretions. PMID- 1747250 TI - Short- and long-term effects of transection of the ophthalmic nerve on optokinetic nystagmus in the rabbit. AB - The role of extraocular proprioception in optokinetic nystagmus (OKN) was examined, using adult pigmented rabbits following transection of the ophthalmic branch of the trigeminal nerve. OKN was induced by rotation of a drum at an angular velocity of 0.85 and 3.7 degrees/s. The eye on the operated side showed a delay in the transition from the OKN-induced quick phase to the slow phase regardless of closure of the eye on either the operated or unoperated side. In addition, the eye on the operated side showed an anticompensatory response in the vestibulo-ocular reflex (VOR) with an unstable drift in the dark. The above abnormalities in OKN and VOR following rhizotomy disappeared after 1-1.5 months. These results suggest that proprioception in the extraocular muscle plays an important role in the fine regulations of eye position for gaze accuracy. The recovery demonstrated appears to be due to a compensatory mechanism in the central nervous system. PMID- 1747251 TI - Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound. AB - Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error. PMID- 1747252 TI - Auditory-evoked brain-stem responses and auditory disorders in patients with Bell's palsy. AB - Out of 121 patients examined with acute unilateral facial paralysis, 93 were determined to have idiopathic facial palsy (Bell's palsy). The examination included pure-tone and speech audiometry, stapedial reflex recordings, temporal bone radiography and auditory-evoked brain-stem response testing (ABR). If a retrocochlear lesion was suspected, computed tomography or magnetic resonance imaging was performed. Patients with sensorineural hearing loss affecting all frequencies were compared to one group with hearing loss affecting only high frequencies and to another group with ABR findings suggesting a cochlear lesion. No association could be made between the etiology of these pathological results and the concurrent facial paresis. Most of them were probably caused by unrelated disorders of the auditory system. In cases with prolonged inter-peak latencies representing brain-stem responses, abnormal ABRs could be caused by the same pathology as the paralysis. This might well suggest the presence of a neuropathy in both the central auditory system and the facial tracts. PMID- 1747253 TI - The Hannover auditory brainstem implant: a multiple-electrode prosthesis. PMID- 1747254 TI - Cavernous sinus thrombosis following odontogenic and cervicofacial infection. AB - Cavernous sinus thrombosis (CST) is rarely seen clinically as a complication of infectious processes since the discovery of penicillin. At the present time, dental abscess is an uncommon cause of CST. We now report our experiences with a 60-year-old diabetic male, who developed CST 38 days after extraction of an infected upper third molar tooth. The importance of eradicating regional cervicofacial foci of infection is stressed. PMID- 1747255 TI - [Therapy of congestive cardiac insufficiency. A challenge]. PMID- 1747256 TI - [Transcutaneous pacemaker in cardiovascular emergencies]. AB - OBJECTIVES AND DESIGN OF THE STUDY: Retrospective study to evaluate the efficacy and tolerance of the transcutaneous cardiac pacemaker in the urgent treatment of asystole or severe bradycardia. SETTING: Coronary Care Unit (CCU) and emergency area of the central reference Hospital. PATIENTS: 24 patients, 20 males and four females, aged between 57 and 84 years (mean 70.4 +/- 7.9). Five pts were in asystole and 19 in severe bradycardia. INTERVENTIONS: The transcutaneous pacemaker used, was the "Cardio Aid Zoll NTP" model. The intensity of the electrical stimulation was increased progressively, until electrical capture or intolerable discomfort by the patients was achieved. We defined by electric efficacy, the visualization of pacing spike followed by a deflection due to ventricular depolarization; and by hemodynamic efficacy, the evidence of myocardial contraction, defined as a palpable pulse, synchronous with the pacing artefact. MAIN RESULTS: Stimulation threshold ranged from 30 to 140 mA (mean 67.7 +/- 23.4). The duration of pacing was from 15 minutes to 13 hours, being more than one hour in only four situations. From the 20 conscious patients, or the ones who got conscious, 15 (75%) tolerated well the stimulation. It was intolerable in five pts (25%). No significative side effects due to the use of transcutaneous pacemaker were observed. CONCLUSIONS: The transcutaneous pacemaker was efficient in the electric and hemodynamic stabilization in the majority of patients. It was generally well tolerated and without important side effects. We think that it may be a valid alternative to transvenous pacing technics in the treatment of asystole and severe bradycardia situations. PMID- 1747257 TI - [Rupture of the intraventricular septum and free wall of the left ventricle secondary to non-penetrating thoracic injury. Doppler echocardiography diagnosis]. AB - The heart is often injured in the setting of blunt chest trauma with a broad spectrum of cardiac lesions. We present a twenty-nine years old man with interventricular septal and rupture and left ventricular free wall rupture following chest trauma. Doppler echocardiography was essential in the diagnostic and therapeutic procedure. We concluded that Doppler-echocardiography must be performed in all patients with suspicion of cardiac affectation after blunt chest trauma. PMID- 1747258 TI - [Myocardial infarct in a young man with normal coronary vessels: apropos of a clinical case treated with streptokinase]. AB - The authors report a case of a 31 year old young man who suffered acute myocardial infarction and was subjected to early treatment with streptokinase. The immediate follow-up showed a complete recanalization of the infarct-related vessel, without any identifiable obstructive lesion on coronary arteriography. Related to this angiographic finding, common in myocardial infarction in the young adult, the authors debate the implicated mechanisms, focusing essentially in the relation endothelium-platelets-vasomotricity. The issue of cigarette smoking as a risk factor and its possible pathogenic implication, even in the absence of atherosclerotic plaque, is also approached. PMID- 1747259 TI - [Surgical therapy of infectious endocarditis]. PMID- 1747260 TI - [Arterial hypertension, insulin resistance, and disorders of membrane permeability]. PMID- 1747261 TI - [Antithrombin III. Physiologic, physiopathologic and laboratory aspects]. AB - Hemostatic control is based in a delicate balance between the activities of activator enzymes and their inhibitors, each one depending on a large number of proteins. Plasma Antithrombin III (ATIII) is one of the most important coagulation inhibitors and the fundamental enzyme for the therapeutical action of heparin. In the last years it was well established that ATIII deficiency accounts for a thrombotic state and inefficiency of heparin therapy. In this work, the authors review the biology of ATIII including its biochemical nature, its physiology, physiopathology and mechanism of action, analysing the implications of its deficiency. The authors draw the attention on clinical and laboratory studies that analyse the prevalence and importance of congenital and acquired deficiency of ATIII, in relation to the prevalence of venous thrombosis. Finally, the laboratory methods applied to the study of ATIII and to the biological control of heparin therapy are described with emphasis on the importance of the ATIII concentrates on this type of treatment. Also the fundamental aspects of heparin resistance are specially mentioned. PMID- 1747262 TI - General practice and the future of obstetric care. PMID- 1747263 TI - Stroke and the carer. PMID- 1747264 TI - Putting on the style: what patients think of the way their doctor dresses. AB - The aim of this study was to determine how acceptable patients found different styles of doctors' dress and whether patients felt that a doctor's style of dress influenced their respect for his or her opinion. A total of 475 patients from five general practices in Lothian were surveyed using photographs of different styles in a male and female doctor and questions about their attitudes to doctors' dress in general. Overall, patients seemed to favour a more formal approach to dress, with the male doctor wearing a formal suit and tie and the female doctor in a white coat scoring the most high marks. This was particularly true of older patients and those in social classes 1 and 2. The male doctor wearing a tweed jacket and informal shirt and tie scored fewer low marks and this was therefore the least disliked of the outfits. There was a marked variation between preferences of patients registered with different practices. When asked, 28% of patients said they would be unhappy about consulting one of doctors shown, usually the ones who were informally dressed. However, some patients said they would dislike their doctor wearing a white coat. Although there are more important attributes for a general practitioner than the way he or she dresses, a majority of patients (64%) thought that the way their doctor dressed was very important or quite important. Given that 41% of the patients said they would have more confidence in the ability of one of the doctors based on their appearance it would seem logical for doctors to dress in a way that inspires confidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747265 TI - Study of the management of chlamydial cervicitis in general practice. AB - The role of the general practitioner in the detection and management of Chlamydia trachomatis infections of the cervix is uncertain. The management by the primary care team of women presenting with lower genital tract symptoms has therefore been studied in one suburban practice. Of 386 women presenting with lower genital tract symptoms over the two year study period 25 (6%) had a positive cervical MicroTrak (Syva) test for Chlamydia trachomatis. Twenty four of these chlamydia positive patients were given their results and treatment by the practice. Twenty two women returned for a follow-up MicroTrak test after treatment and two of these patients (9%) had a positive test following treatment. A review of the patients' notes indicated that contact tracing had been discussed with 22 of the 25 chlamydia positive patients. The results of the management of chlamydial cervicitis by this primary health care team are acceptable when compared with studies from hospital clinics. Provided the primary care team has access to facilities for the diagnosis of C trachomatis and can follow up non-attenders to ensure they receive their results, provide information about contact tracing and follow up positive patients then chlamydial cervicitis can be managed in general practice. PMID- 1747266 TI - Survey and audit of diabetes care in general practice in south London. AB - A survey was made of the diabetic care given by general practitioners in six family practitioner committee areas. Replies were received from 388 practices, representing 1034 principals (effective response rate 69%), serving over two million patients. Fourteen per cent of practices offered mini-clinic facilities for their diabetic patients, although a much greater proportion professed to give either full or shared care to patients in ordinary surgery time. One quarter of practices kept a diabetes register, but fewer had a system of recall for patients to ensure anticipatory care. The barriers which general practitioners most often perceived in the provision of adequate care for diabetics were: lack of time, absence of a recall system and deficiency in their own clinical skills. Seventy seven of the doctors responding to the initial questionnaire participated in an audit of the level of supervision provided for 378 of their diabetic patients. Better levels of supervision of non-insulin dependent diabetics were shown in those practices where diabetes registers were kept, and where special arrangements were made for caring for diabetes. The levels of care provided by those doctors setting aside specific clinic times were not demonstrably superior to those who did not. The findings suggest that provision of support services, particularly expertise in dietetics, would help to increase general practitioners' confidence and enable more of them to improve their care of diabetic patients. PMID- 1747267 TI - Long-term follow up of patients with gastritis associated with Helicobacter pylori infection. AB - The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation. PMID- 1747268 TI - Patient education about cough: effect on the consulting behaviour of general practice patients. AB - The aim of this general practice study was to examine how the consulting behaviour of patients with a cough was affected when the tasks and responsibilities of patients, practice nurses and general practitioners were reorganized. In four 'average' single-handed general practices the effects on the consulting behaviour of patients of a rational practice policy on cough and the provision of systematic patient education on cough were compared with patient behaviour in four matched control practices. Changes of behaviour were measured in 548 patients who consulted for cough at least twice, in two successive autumn winter periods. Significantly more patients in the experimental practice changed their behaviour to follow the practice guidelines than did patients in the control practices (56% versus 30%, P less than 0.001). The proportion of patients who continued to consult in the approved manner was greater among patients receiving intervention (66% versus 29%, P less than 0.001). This was equally true for patients who had suffered less than four episodes of cough or more than four episodes. The more often the patients received the education, the more effective it was. All patients who consulted the general practitioner for cough during the first autumn-winter period filled in a cough diary during the second period. From this it appeared that the intervention did not result in patients delaying consultation when they had a cough lasting longer than three weeks or one with 'serious' symptoms. It would appear that a rational practice policy and the provision of patient education can stimulate patients to modify their consulting behaviour. This could result in a reduction in the costs of health care. PMID- 1747269 TI - How well do family practitioner committee and general practice records agree? Experience in a semi-rural practice. AB - General practice notes may be inaccurate for various reasons. A study was carried out in one semi-rural practice to investigate the agreement between records held by the family practitioner committee and those kept in the practice. Details on the practice notes and the family practitioner committee list were compared for 800 patients. The details examined included name, sex, date of birth, address and National Health Service number. While 58% of records agreed, discrepancies occurred in 339 records (42%). The most common discrepancies concerned the patient's address (30.6%), date of birth (9.4%) and NHS number (8.0%). Nearly 5% of the practice notes appeared to be for patients who were no longer on the practice list or dependent on its care. These findings have implications under the new general practitioner contract where screening programmes, target related payments, and increased capitation fees require accurate practice records. PMID- 1747270 TI - William Pickles Lecture 1991. My brother's keeper. PMID- 1747271 TI - Hepatitis B transmission within families. PMID- 1747272 TI - Assessment of cognitive impairment in the elderly. PMID- 1747273 TI - Which antidepressant? PMID- 1747274 TI - Using skeletal muscle to assist the heart. PMID- 1747275 TI - Vascular tone in heart failure: the neuroendocrine-therapeutic interface. PMID- 1747276 TI - Relation between cyclic variation in echo amplitude and segmental contraction in normal and abnormal hearts. AB - OBJECTIVE: To study the relation between cardiac systolic activity and cardiac cycle dependent variation in the ultrasound signal arising from within the myocardium. DESIGN: Regional echo amplitude was used as a measure of the myocardial ultrasound signal. Relative echo amplitude values were assigned by standardising echo gain using the posterior parietal pericardium as an in-vivo calibration. M mode measurements of the left ventricle were used to assess cardiac systolic activity. Subjects were studied prospectively. Analysis of echo amplitude was performed by investigators who were blinded to the results of the M mode analysis. The influence of impaired left ventricular performance and abnormal wall motion were assessed. PATIENTS: 11 cardiomyopathy patients with impaired ventricular function, eight patients with severe pulmonary hypertension and reversed septal motion, and 19 healthy controls. SETTING: All subject studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. MAIN OUTCOME MEASURES: Cyclic variation in echo amplitude was determined as the change in echo amplitude from end diastole to end systole. Additionally, an index of cyclic variation defined as the ratio of the cyclic change in echo amplitude to end diastolic echo amplitude was measured. Both cyclic variation and the cyclic variation index were analysed to see whether they correlated with left ventricular dimensions, fractional shortening, and systolic wall thickening. RESULTS: Stepwise regression analysis showed systolic wall thickening to be the most significant independent variable that correlated with the cyclic variation index for both the septum and posterior wall (r = 0.68, p = 0.0001, septum; r = 0.69, p = 0.0001, posterior wall). The slopes and intercepts for both regression equations were similar (y = 0.005x + 0.006, septum; y = 0.006x + 0, posterior wall). Subgroup analysis showed that the healthy controls, patients with cardiomyopathy, and patients with pulmonary hypertension had similar slopes and intercepts for their individual regression equations. CONCLUSIONS: These data support the hypothesis of a quantitative relation between the extent of cyclic variation of echo amplitude and the degree of segmental myocardial shortening, as measured by systolic wall thickening, which is not significantly influenced by location within the myocardium, left ventricular performance, or wall motion. They provide further evidence of the usefulness of quantitative analysis of myocardial echo amplitude in the study of regional myocardial function in both normal and injured myocardium. PMID- 1747277 TI - Responsiveness of raised pulmonary vascular resistance to oxygen assessed by pulsed Doppler echocardiography. AB - OBJECTIVE: To assess whether changes in Doppler echocardiographic indices in the pulmonary artery correlated with changes in pulmonary vascular resistance. DESIGN: Acceleration time, ejection time, maximal flow velocity, and velocity time integrals were measured at the same time as pressure and oxygen saturation measurements in room air and during 10 minutes of oxygen breathing in the catheterisation laboratory. Pulmonary vascular resistance and pulmonary blood flow (Qp) were calculated from catheterisation data by use of the Fick principle. PATIENTS: 14 consecutive patients with a congenital heart defect and a left to right shunt associated with raised pulmonary artery pressure who underwent routine diagnostic cardiac catheterisation to assess their pulmonary vascular resistance. RESULTS: Though pulmonary vascular resistance and systolic pulmonary artery pressure fell significantly during oxygen administration, there was no significant change in the acceleration time or ejection time. Peak velocity increased significantly during oxygen administration. During oxygen breathing Doppler derived measurements of pulmonary flow showed a significant increase in Qp similar to the increase in Qp measured by the Fick principle. There was no significant correlation between the fall in pulmonary vascular resistance and the increase in acceleration time or ejection time, increase in peak velocity, increase in pulmonary artery diameter, or increase in Doppler derived pulmonary blood flow. CONCLUSIONS: Measurements of acceleration and ejection time by Doppler echocardiography did not predict the response of pulmonary artery pressure and resistance to oxygen. Though changes in maximal flow velocity across the pulmonary artery and in Doppler derived pulmonary blood flow measurements became significant during oxygen breathing, the correlation of these changes with fall in pulmonary vascular resistance was poor. PMID- 1747278 TI - Transoesophageal echocardiographic assessment of fixed subaortic obstruction in children. AB - OBJECTIVE: To evaluate the clinical usefulness of transoesophageal echocardiography in the assessment of children with fixed left ventricular outflow tract stenosis. PATIENTS AND METHODS: Eight consecutive children, aged over 5 years, with fixed subaortic stenosis and one child with fixed subpulmonary left ventricular outflow tract stenosis were prospectively assessed by precordial and transoesophageal echocardiography. RESULTS: Transoesophageal images of the left ventricular outflow tract were much clearer than precordial images in all patients except one with a prosthetic mitral valve. Improved visualisation provided further information on the nature of the lesion (additional chordal attachment of the mitral valve in one, accessory atrioventricular valve tissue with aneurysm formation in one), on the extent of the lesion (circumferential in three), and on the very close relation of a ridge to the aortic valve leaflets in one. Transoesophageal Doppler did not provide any additional information on aortic regurgitation and was unreliable for gradient estimation across the left ventricular outflow tract. CONCLUSIONS: Transoesophageal imaging provides an excellent means of visualising lesions in the left ventricular outflow tract and can be useful in a few children and adolescents in whom precordial echocardiography does not provide adequate information. The technique can also be used intraoperatively to define the full extent of the obstructive lesion and to assess residual lesions after surgery. PMID- 1747279 TI - Assessment of right and left ventricular function in terms of force development with gestational age in the normal human fetus. AB - OBJECTIVE: To assess right and left ventricular systolic function in normal human fetuses by cross sectional Doppler echocardiography to calculate the force developed by myocardial shortening. DESIGN: Cross sectional echocardiographic images of the aorta and pulmonary arteries were obtained prospectively in order to measure great vessel diameters and calculate their cross sectional areas. Doppler velocity signals were recorded from the proximal aorta and the proximal pulmonary artery and digitised to obtain peak velocity, acceleration time, flow velocity time integral during acceleration, and the flow velocity time integral for the whole of ejection. Right and left ventricular force development was estimated by Newton's equation in which force is defined as the product of mass and acceleration. PATIENTS: 58 normal human fetuses at a gestational age of from 20 to 42 weeks. RESULTS: The cross sectional area of the pulmonary artery was 20% greater than that of the aorta. Aortic acceleration time was longer than that in the pulmonary artery, and peak blood flow velocity in the aorta was consistently greater than that in the pulmonary artery. Right ventricular stroke volume was significantly greater than left ventricular stroke volume. The force developed by the right and left ventricles was, however, similar throughout the gestational period studied, increasing tenfold from 20 weeks' gestation to term (r = 0.74, p less than 0.0001; r = 0.75, p less than 0.0001) respectively. CONCLUSION: The development of right and left ventricular force in the human fetus is similar in spite of the greater volume handled by the right ventricle. This index of ventricular performance does not require calculation of ventricular volume and because it varies independently of ventricular geometry and heart rate it should prove useful in assessing cardiac function in the normal human fetus and in fetuses with ventricular dysfunction. PMID- 1747280 TI - Non-invasive measurement of the regurgitant fraction by pulsed Doppler echocardiography in isolated pure mitral regurgitation. AB - OBJECTIVE: To assess the usefulness of pulsed Doppler echocardiography as a method of measuring the regurgitant fraction in patients with mitral regurgitation. PATIENTS AND METHODS: Twenty controls and 27 patients with isolated mitral regurgitation underwent Doppler studies. In the patients the study was performed within 48 hours of cardiac catheterisation. Aortic outflow was measured in the centre of the aortic annulus, and mitral inflow was derived from the flow velocity at the tip of the leaflets and the area of the elliptical mitral opening. The regurgitant fraction was calculated as the difference between the two flows divided by the mtiral inflow. RESULTS: In the 20 controls the two flows were almost identical (mitral inflow, 4.44 (SD 0.88) l/min; aortic outflow, 4.58 (SD 0.84) l/min), with a mean regurgitant fraction of 4.2 (SD 8.4)%. In patients with mitral regurgitation, the mitral inflow was significantly higher than the aortic outflow (8.8 (3.6) v 4.3 (1.1) l/min). In most patients the Doppler-derived regurgitant fraction (45.8 (19.2)%) accorded closely with the regurgitant fraction (41.3 (SD 17.8)%) determined by the haemodynamic technique. CONCLUSION: Pulsed Doppler echocardiography, with an instantaneous velocity-valve area method for calculating mitral inflow, reliably measured the severity of regurgitation in patients with mitral regurgitation. PMID- 1747281 TI - Reduced exercise capacity in patients with tricuspid regurgitation after successful mitral valve replacement for rheumatic mitral valve disease. AB - OBJECTIVE: To determine how severe tricuspid regurgitation influences exercise capacity and functional state in patients who have undergone successful mitral valve replacement for rheumatic mitral valve disease. DESIGN: 9 patients in whom clinically significant tricuspid regurgitation developed late after mitral valve replacement were compared with 9 patients with no clinical evidence of tricuspid regurgitation. The two groups were matched for preoperative clinical and haemodynamic variables. Patients were assessed by conventional echocardiography, Doppler echocardiography, and a maximal treadmill exercise test in which expired gas was monitored by mass spectrometry. SETTING: University Hospital of Wales, Cardiff. SUBJECTS: 18 patients who had been reviewed regularly since mitral valve replacement. MAIN OUTCOME MEASURE: Objective indices of exercise performance including exercise duration, maximal oxygen consumption, anaerobic threshold, and ventilatory response to exercise. RESULTS: Mitral valve prosthetic function was normal in all patients and estimated pulmonary artery systolic pressure and left ventricular function were similar in the two groups. Right ventricular diameter (median (range) 5.0 (4.3-5.6) v 3.7 (3.0-5.4) cm, p less than 0.01) and the incidence of paradoxical septal motion (9/9 v 3/9, p less than 0.01) were greater in the group with severe tricuspid regurgitation. Exercise performance--assessed by exercise duration (6.3 (5.0-10.7) v 12.7 (7.2-16.0) min, p less than 0.01), maximum oxygen consumption (11.2 (7.3-17.8) v 17.7 (11.8-21.4) ml min-1 kg-1, p less than 0.01), and anaerobic threshold (8.3 (4.6-11.4) v 0.7 (7.3-15.5) ml min 1 kg-1, p less than 0.05)--was significantly reduced in the group with severe tricuspid regurgitation. The ventilatory response to exercise was greater in patients with tricuspid regurgitation (minute ventilation at the same minute carbon dioxide production (41.0 (29.9-59.5) v 33.6 (26.8-39.3) l/min, p less than 0.01). CONCLUSIONS: Clinically significant tricuspid regurgitation may develop late after successful mitral valve replacement and in the absence of residual pulmonary hypertension, prosthetic dysfunction, or significant left ventricular impairment. Patients in whom severe tricuspid regurgitation developed had a considerable reduction in exercise capacity caused by an impaired cardiac output response to exercise and therefore experienced a poor functional outcome. The extent to which this was attributable to the tricuspid regurgitation itself or alternatively to the consequences of right ventricular dysfunction was not clear and requires further investigation. PMID- 1747282 TI - Quinine and quinidine. PMID- 1747283 TI - Role of transoesophageal echocardiography in evaluation of cardiogenic embolism. AB - OBJECTIVE: To determine the value of transoesophageal echocardiography in the assessment of selected patients at risk of cardiogenic embolism or after it. DESIGN: Prospective comparison of the results of transoesophageal and transthoracic echocardiography. Transoesophageal echocardiography was performed with a 5 MHz single plane phased array transducer. SETTING: University teaching hospital. PATIENTS: 100 patients referred for transoesophageal echocardiography after a cerebral ischaemic event or peripheral arterial embolism (n = 63), before percutaneous balloon dilatation of the mitral valve (n = 23), or before electrical cardioversion of atrial fibrillation (n = 14). RESULTS: Transthoracic echocardiography showed potential sources of embolism in four patients including left ventricular thrombus in two patients (with one false positive), left atrial appendage thrombus (n = 1), and patent foramen ovale (n = 1). Transoesophageal echocardiography showed 59 potential embolic sources in 45 patients including left atrial spontaneous echo contrast (n = 33), left atrial appendage thrombus (n = 13), left ventricular thrombus (n = 5), patent foramen ovale (n = 3), left ventricular spontaneous echo contrast (n = 2), mitral valve prosthesis thrombus (n = 1), mitral valve prolapse (n = 1), and pronounced aortic atheroma (n = 1). Transoesophagal echocardiography showed potential embolic sources in 36/53 (68%) patients with atrial fibrillation compared with 9/47 (19%) patients in sinus rhythm. Percutaneous balloon dilatation of the mitral valve was performed without embolic complications in 18 patients without left atrial thrombi and in three patients with small fixed thrombi in the left atrial appendage. It was cancelled in two patients with large thrombi in the left atrial appendage. Cardioversion was performed without embolic complications in 14 patients without left atrial thrombi. CONCLUSIONS: Transoesophageal echocardiography detects potential sources of embolism better than transthoracic echocardiography in selected patients at risk of cardiogenic embolism or after it. PMID- 1747284 TI - DiGeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin. AB - DiGeorge syndrome was diagnosed in an infant who had an interrupted aortic arch, hypoparathyroidism, and low T lymphocyte numbers. Two siblings had heart defects that are not commonly described in DiGeorge syndrome (a membranous ventricular septal defect and coarctation of the aorta respectively). These siblings did not have evidence of thymic dysfunction or hypoparathyroidism. Chromosome analysis showed that the mother, whose cardiovascular examination was normal, and her three offspring with heart defects had a 22q11 interstitial deletion, which was confirmed by molecular analysis. This family suggests that 22q11 deletions can cause apparently isolated heart defects and that the range of these defects may be wider than previously recognised. Once the genes that are deleted in this family are characterised they will be useful candidate genes in the investigation of isolated cardiac malformations. PMID- 1747285 TI - Silent ischaemia in diabetic men with autonomic neuropathy. AB - Autonomic neuropathy is associated with an increased incidence of silent myocardial infarction and sudden death. The purpose of this study was to investigate the prevalence of silent myocardial ischaemia in diabetic patients with autonomic neuropathy and without. Five standard autonomic function tests were performed on 41 men with diabetes: postural change in blood pressure, postural change in heart rate, heart rate response to deep breathing, heart rate response to Valsalva's manoeuvre, and blood pressure response to sustained handgrip. There were 17 patients with autonomic neuropathy (group A) and 24 with normal autonomic function (group B). All patients underwent 24 hour ambulatory electrocardiographic monitoring to detect silent ischaemia. There was no significant difference in risk factors for coronary artery disease or history of angina pectoris between these groups. The prevalence of silent ischaemia was 64.7% in group A (95% confidence interval (95% CI) 38.33 to 85.79%) and 4.1% in group B (95% CI 0.11 to 21.12%). This represents a relative risk of 42.2 (95% CI 4.5 to 39.4, p less than 0.001). These results are consistent with the concept that autonomic neuropathy may prevent the development of anginal pain and thus obscure the presence of ischaemic heart disease. Twenty four hour ambulatory electrocardiographic monitoring may identify a subgroup of diabetic patients with autonomic neuropathy who have myocardial ischaemia and to whom treatment may be offered. PMID- 1747286 TI - Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease. AB - The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic. PMID- 1747287 TI - Paradoxical embolisation of a catheter fragment to a coronary artery in an infant with congenital heart disease. AB - Six weeks after cardiac catheterisation via the right femoral vein an infant underwent an anatomical correction for transposition of the great vessels and closure of a large ventricular septal defect. The patient died intraoperatively as a result of severe left ventricular dysfunction. Necropsy showed an old myocardial infarction associated with thrombosis of the circumflex coronary artery. Electron probe x ray analysis showed that foreign refractile material within the thrombus contained bismuth, an element used in the construction of some cardiac catheters. This is believed to be the first report of "paradoxical" coronary embolisation of catheter-derived material and highlights the usefulness of electron probe x ray analysis. PMID- 1747288 TI - John Fothergill and angina pectoris. PMID- 1747289 TI - Coronary angioplasty in the United Kingdom. Report of a Working Party of the British Cardiac Society. PMID- 1747290 TI - Management of patients with Bjork-Shiley prosthetic valves. PMID- 1747291 TI - Heart valve surgery in the United Kingdom: present practice and future trends. PMID- 1747292 TI - Short and long term results after intracoronary stenting in human coronary arteries: monocentre experience with the balloon-expandable Palmaz-Schatz stent. AB - OBJECTIVE: Intracoronary stenting was designed to overcome acute complications after percutaneous transluminal coronary angioplasty and to achieve a reduced rate of restenosis, both of which are major limitations of this well accepted method for treating coronary heart disease. This report describes the experience at one centre with the implantation of balloon-expandable Palmaz-Schatz stents and focuses on device related complications and the short and long term angiographic outcome. DESIGN: A retrospective data analysis. PATIENTS: Stenting was attempted in 50 patients. Restenosis after an initially successful angioplasty procedure, inadequate postangioplasty results, saphenous coronary bypass stenoses, and bail-out situations were regarded as indications. MAIN OUTCOME MEASURES AND RESULTS: In 49 of 50 attempted patients 61 stents (1-4 per patient) were implanted. Delivery problems occurred in three patients and were successfully overcome in two patients. Bail-out situations were successfully managed in 16 patients. Complications included acute thrombus formation within the stent immediately after implantation in one patient, which was successfully treated by thrombolysis. One patient was sent for bypass surgery the day after implantation; another died 10 days after implantation for unknown reasons. Subacute stent thrombosis occurred in seven patients 5-9 days after implantation and was successfully treated by thrombolysis or balloon angioplasty in five patients. Bleeding complications occurred in nine patients, five of whom required blood transfusions. Angiography showed long term vessel patency after 4-6 months in 31 (76%) of the 41 patients who were followed up, restenosis in six (14%), and reocclusion in four (10%). Late restenosis or reocclusion was found in five (15%) of 33 patients with a single stent in contrast to five (63%) of eight patients with multiple stents. CONCLUSIONS: Balloon-expandable intracoronary stenting is a feasible method for treating the acute complications of balloon angioplasty. It reduced the rate of restenosis for single stent implantation. Subacute thrombotic events must be regarded as previously unknown and serious complications. PMID- 1747293 TI - Changes in Doppler indices of cardiac function during and after percutaneous transluminal coronary angioplasty. AB - OBJECTIVE: To assess the sensitivities of Doppler indices to changes in global cardiac function during and after controlled myocardial ischaemia induced by coronary angioplasty. DESIGN: Continuous wave Doppler signals of aortic flow were recorded during coronary angioplasty. The following Doppler indices of cardiac function were measured before, during, and after balloon inflation: V (peak velocity), MA (mean acceleration), V2/T (T = time from onset to peak ejection), and MD (minute distance corrected for baseline heart rate). SETTING: A tertiary care cardiological unit in a university hospital. PATIENTS: Sixteen patients undergoing coronary angioplasty of the left anterior descending coronary artery. Eight patients had multivessel disease. MAIN OUTCOME MEASURES: The primary outcome measures were planned before data collection began. RESULTS: 12 patients showed a significant fall of three or more Doppler indices from their baseline values during balloon inflation. This occurred in all patients with multivessel disease. The Doppler indices V2 T, MD, V, and MA fell by 43.7%, 37.7%, 27.4%, and 23% respectively from their baseline values (p less than 0.0001). The relative sensitivities of the Doppler indices to ischaemia were V2/T greater than MD (p less than 0.02), MD greater than (p less than 0.001), and V greater than MA (p less than 0.01). The impairment of global left ventricular function resulting from brief balloon inflation during single vessel angioplasty was reversible in all the patients. CONCLUSIONS: The Doppler indices V2/T, MD, V, and MA are all sensitive, in order of magnitude, to falls in global cardiac function resulting from ischaemia. They may prove useful for assessing cardiac function during ischaemia in the clinical setting. PMID- 1747294 TI - von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. AB - OBJECTIVE: To evaluate as predictors of reinfarction and mortality tissue plasminogen activator antigen and activity before and after venous occlusion, plasminogen activator inhibitor, von Willebrand factor, and established risk factors. DESIGN: Prospective study with a mean observation time of 4.9 years. SETTING: Secondary referral centre, the Department of Internal Medicine, University Hospital of Umea. PATIENTS: 123 consecutive survivors of myocardial infarction under the age of 70 years. MAIN OUTCOME MEASURES: Reinfarction and deaths from all causes. RESULTS: 23 patients died and 36 patients had at least one reinfarction. High concentrations of von Willebrand factor were independently associated with both reinfarction and mortality. A history of angina at entry into the study was also independently associated with reinfarction and mortality. Hypertension was independently associated with mortality but not with reinfarction. None of the fibrinolytic or lipid variables was associated with reinfarction or death. CONCLUSION: A high concentration of von Willebrand factor was a novel index of increased risk for reinfarction and mortality in survivors of myocardial infarction. PMID- 1747295 TI - Increased concentrations of tumour necrosis factor in "cachectic" patients with severe chronic heart failure. AB - OBJECTIVE: To ascertain whether patients with cardiac failure and reduced body weight ("cardiac cachexia") have increased circulating concentrations of tumour necrosis factor (cachectin). DESIGN: Patients with cardiac failure were prospectively identified as "cachectic" (body fat less than 27% in men and less than 29% in women measured by skinfold thickness callipers) or "non-cachectic". Tumour necrosis factor was assayed blind to patient group. SETTING: Cardiology unit in a tertiary referral centre. PATIENTS: 26 consecutive patients (10 women) (mean age 61) admitted for investigation or treatment of chronic heart failure. All were in New York Heart Association class III or IV. RESULTS: In nine of the 16 cachectic patients the concentration of tumour necrosis factor was increased (mean (SEM) 74 (20) pg/ml) compared with one of the 10 "non-cachectic" patients (22 pg/ml, p less than 0.001). Patients with a raised circulating concentration of tumour necrosis factor weighed significantly less (55.6 (3.5) kg) than those in whom the concentration of tumour necrosis factor was normal (69.0 (4.1) kg) (p = 0.02). CONCLUSIONS: Circulating concentrations of tumour necrosis factor were increased in a significant proportion of patients with chronic heart failure and low body weight. Tumour necrosis factor stimulates catabolism experimentally and it may be a factor in the weight loss seen in patients with "cardiac cachexia". PMID- 1747296 TI - Myocardial bridges: morphological and functional aspects. AB - OBJECTIVE: To assess the arrangement of myocardial bridges. DESIGN: A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS: Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS: The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia. PMID- 1747297 TI - Pregnancy outcome and Ebstein's anomaly. AB - BACKGROUND: Ebstein's anomaly is an uncommon congenital cardiac abnormality that may be associated with cyanosis and arrhythmias. For those female patients with the anomaly who survive to adult life there is little information available about pregnancy, maternal complications, and fetal outcome. This study was designed to address this issue so that these patients can receive appropriate advice and management. METHODS AND RESULTS: Forty two pregnancies in 12 women with Ebstein's anomaly were studied. The mothers' cardiac lesions were assessed on the basis of symptoms, the presence of cyanosis or arrhythmia, and by echocardiographic grading of severity. In the absence of important maternal cyanosis or arrhythmia, pregnancy was well tolerated. Neonatal outcome was good though there was an increased risk of prematurity and dysmaturity in the babies born to mothers with cyanosis. CONCLUSIONS: This study indicates that women with Ebstein's anomaly who reach child-bearing age can be advised that pregnancy is likely to be well tolerated with good fetal outcome. Maternal arrhythmia or cyanosis are indications for closer maternal and fetal observation. PMID- 1747298 TI - Doppler echocardiographic evaluation of pulmonary blood flow after the Fontan operation: the role of the lungs. AB - OBJECTIVE: To document whether the act of respiration influences pulmonary blood flow in patients after the Fontan operation. DESIGN: Prospective study in which patients acted as their own controls. SETTING: Supraregional paediatric cardiology centre. PATIENTS: Sixteen patients who had undergone atriopulmonary anastomosis (Fontan operation) for the treatment of congenital heart disease. INTERVENTION: Doppler assessment of pulmonary artery flow patterns with a simultaneous respirometer, electrocardiogram and phonocardiogram. RESULTS: Total (mean (1SD) ) forward pulmonary flow was 63.6 (35)% higher during inspiratory cardiac cycles than during expiratory ones. CONCLUSIONS: The act of breathing provides an additional energy supply to pulmonary blood flow in patients after the Fontan operation. PMID- 1747299 TI - Abnormal patterns of intraventricular flow and diastolic filling after the Fontan operation: evidence for incoordinate ventricular wall motion. AB - OBJECTIVE: To assess whether regional abnormalities of ventricular function are present in patients after the Fontan operation and to explore the implications of any such abnormalities for ventricular filling. DESIGN AND PATIENTS: Prospective study in which 25 patients after the Fontan operation were compared with 25 healthy controls and 12 patients with a univentricular atrioventricular connection, before the Fontan operation. INTERVENTIONS: Doppler echocardiography, with simultaneous electrocardiogram, phonocardiogram, and respirometer. RESULTS: Isovolumic relaxation time was significantly longer in patients after the Fontan operation than in normal children (p less than 0.001) or the preoperative patients (p = 0.001). Systolic intraventricular flow was detected in 60% of patients after the Fontan operation and in 42% of preoperative patients. After the Fontan operation 80% of patients showed intraventricular flow during isovolumic relaxation compared with 8% of normal children and none of the preoperative patients. CONCLUSIONS: Incoordinate ventricular relaxation is common after the Fontan operation. This may have important implications for ventricular diastolic filling, pulmonary blood flow, and cardiac output in these patients. PMID- 1747300 TI - Echocardiographic and angiographic diagnosis of Ebstein's anomaly of the mitral valve. AB - A rare case of Ebstein's anomaly of the mitral valve was diagnosed by cross sectional echocardiography and angiography. PMID- 1747301 TI - Double outlet left ventricle: diagnosis with magnetic resonance imaging. AB - A complex congenital cardiac malformation in a female patient was evaluated several times by angiocardiography and echocardiography in childhood but a definite diagnosis was not established. Segmental analysis of the heart and the great vessels by magnetic resonance imaging when the patient was 34, however, showed a double outlet left ventricle in which the aorta was situated anterior to and to the left of the pulmonary trunk and an associated subaortic ventricular septal defect with pulmonary valve stenosis. This is the first time that this extremely rare cardiac malformation has been diagnosed by magnetic resonance imaging. PMID- 1747302 TI - Physical activity and ischaemic heart disease in middle-aged British men. AB - OBJECTIVE: To assess the relation between reported physical activity and the risk of heart attacks in middle aged British men. DESIGN: Prospective study of middle aged men followed for a period of eight years (The British Regional Heart Study). SETTING: One general practice in each of 24 British towns. PARTICIPANTS: 7735 men aged 40-59 years at initial examination. END POINT: Heart attacks (non-fatal and fatal). MEASUREMENTS AND MAIN RESULTS: During the follow up period of eight years 488 men suffered at least one major heart attack. A physical activity score used was developed and validated against heart rate and lung function (FEV1) in men without evidence of ischaemic heart disease. Risk of heart attack decreased significantly with increasing physical activity; the groups reporting moderate and moderately vigorous activity experienced less than half the rate seen in inactive men. The benefits of physical activity were seen most consistently in men without preexisting ischaemic heart disease and up to levels of moderately vigorous activity. Vigorously active men had higher rates of heart attack than men with moderate or moderately vigorous activity. The relation between physical activity and the risk of heart attack seemed to be independent of other cardiovascular risk factors. Men with symptomatic ischaemic heart disease showed a reduction in the rate of heart attack at light or moderate levels of physical activity, beyond which the risk of heart attack increased. Men with asymptomatic ischaemic heart disease showed an increasing risk of heart attack with increasing levels of physical activity, but with a progressive decrease in case fatality. Overall, men who engaged in vigorous (sporting) activity of any frequency had significantly lower rates of heart attack than men who reported no sporting activity. However, when all men reporting regular sporting activity at least once a month were excluded from analysis, there remained a strong inverse relation between physical activity and the risk of heart attack in men without pre existing ischaemic heart disease. CONCLUSION: This study suggests that the overall level of physical activity is an important independent protective factor in ischaemic heart disease and that vigorous (sporting) exercise, although beneficial in its own right, is not essential in order to obtain such an effect. PMID- 1747303 TI - Staffing in cardiology in the United Kingdom 1990. Sixth biennial survey: with data on facilities in cardiology in England and Wales 1989. AB - The Sixth Biennial Survey of Staffing in Cardiology was conducted in July 1990. This report summarises the data that were collected, together with the results of a survey of facilities in cardiology made in 1989. The total number of cardiologists in the United Kingdom, defined as individuals trained in the specialty and spending at least 40% of their time working in it, is now 323. Six individuals work part time only, making 320 whole time posts. This number has increased over the two years from 1988 to 1990 by 32, of which 23 work only in the specialty and nine as general physicians with a major interest in cardiology. The rate of increase in numbers over the past decade has been reasonably consistent with an average of approximately 4.4% per year. Thirty one districts in England and Wales still have no cardiologist and 13 other districts have little provision with an average of three (visiting) sessions each per week. The population in these 44 districts is 8.3 million. Scotland also has an inadequate distribution of service in the specialty. If recommendations for cardiac surgery and angioplasty made in the Fourth Report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England are to be met, we calculate that we need 63 more cardiologists in our major centres. To provide one cardiologist in every district hospital and two for larger districts would require 94 more specialists, making a total shortfall of 157 individuals. We have no excess of senior registrars to provide for a major expansion at consultant level. Time spent within the senior registrar (or academic equivalent) grade has tended steadily to decline and very few now reach the end of their contracts. The need for more individuals to pass through the senior registrar grade will be met in part by a planned reduction in the training period to three years. This will be inadequate, however, because projected retirements show that the number of consultant vacancies will increase sharply from 1997. We believe that additional senior registrar posts must be created if a serious shortfall in service provision by consultants is to be avoided. The provision of non-invasive facilities in cardiology is reasonable. The need for additional equipment for invasive cardiology has not been assessed. The number of physiological measurement technicians varies considerably between regions and is generally inadequate. PMID- 1747304 TI - Endothelium in control. PMID- 1747305 TI - Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer. PMID- 1747306 TI - Back school for patients with vertebral fractures. AB - Back school is behavior training for the prevention and treatment of back problems arising from faulty body posture and muscular dysfunction. This paper describes the conception and evaluation of a back school program for patients with vertebral fractures. The curriculum includes the provision of detailed information as well as physiotherapy, training in the right way to perform activities of everyday life, counseling, relaxation training, and self monitoring. From October 1987 to June 1990 214 patients with vertebral fractures completed the back school program. The effectiveness of the program was measured by a knowledge test and a behavior test. The results suggest that this back school is an effective addition to conventional concept using physiotherapy exclusively. PMID- 1747307 TI - Long-term results of tibial plafond fractures treated with open reduction and internal fixation. AB - In this study a series of 41 consecutive cases of operatively treated fractures of the tibial plafond was retrospectively analysed. The fractures were classified into types I (9.75%), II (41.5%) and III (48.75%) as defined by Ruedi. The 10 year average follow-up revealed 66% good and 24% fair objective results overall. The recent literature uniformly reports good results in operatively treated type I and -II fractures. In this series, these essentially low-velocity injuries resulted in a satisfactory outcome in 86% of cases. Controversy exists in reports of operative treatment of type-III fractures. The incidence of satisfactory results in the present series in type-III fractures was 95% good and fair results, which appears to be better than in other authors' experience. This can be partially explained by the relatively few high-velocity injuries (50% of the type-III fractures) and also by certain technical procedures used in surgery to stabilise these fractures. The initial type of fracture and articular cartilage damage are directly related to late arthrosis. There is clear evidence that the quality of reduction correlates with later development of arthrosis. However, anatomical reduction may still be followed by significant joint arthrosis because of articular cartilage damage. Severe arthrosis present at late follow-up did not correlate with poor subjective or objective results. With adequate open reduction and internal fixation, satisfactory results can be obtained in severe tibial plafond fractures. Meticulous soft tissue care and handling at surgery are important. Various fixation devices may need to be incorporated to ensure optimal soft tissue status for fracture healing. PMID- 1747308 TI - Acceleration of wound healing by local application of fibronectin. AB - The process of wound healing under the influence of locally applied fibronectin, heparin and thrombin was studied in adult rabbits. Using immunofluorescence microscopy, a higher concentration of fibronectin within the wound area was found on the 1st day after fibronectin treatment. The tensile strength of the wounds was tested on the 6th, 9th and 12th day after operation. On the 9th day the tensile strength of the fibronectin-treated wounds was significantly higher than that of the control wounds on the 12th day after operation. The addition of heparin and thrombin, each in combination with fibronectin, did not show any significant effect on wound healing. PMID- 1747309 TI - Anterior ankle pain in sports medicine: aetiology and indications for arthroscopy. AB - Persistent pain and swelling in the anterior part of the upper ankle are encountered very frequently in sports traumatology. Classically, in the patient with a long history of typical anterior ankle pain there is no instability, but pinching effects, a sense of impingement, blocking and a feeling of unsteadiness combined with a certain restriction of movement due to the pathology. By analogy with the anatomical structures, various pathologic changes can lead to the classic clinical symptoms: adhesions, cicatrices, meniscoid-type lesions, osteophytes with synovitis, folds, fibrotic subcutaneous fatty tissue, free arthroliths, osteochondral lesions and arthrotic changes. When long-term conservative therapy has not provided a cure for the clinical syndrome surgical intervention becomes necessary. Arthroscopic interventions were carried out in a total of 21 patients, with follow-up times between 6 and 36 months. About two thirds of all the patients showed good or very good results, while in one-third the results were unsatisfactory, mainly because of degenerative changes. An precise diagnosis is essential, but the significance of a pathologic change as the cause of symptoms can be problematical. PMID- 1747310 TI - Lateral band release for post-traumatic extension contracture of the proximal interphalangeal joint. AB - In the patient with scarring of just the central band and lateral bands, there is a loss of active and passive flexion of the proximal interphalangeal (PIP) joint because the lateral bands have lost their normal volar shift. Surgical freeing of the lateral bands from the central band using parallel incisions may be required to allow full flexion of the PIP joint. This study reports on 10 patients with post-traumatic extension contracture of the PIP joint treated by lateral band release. All operations were successful, with an average gain in range of motion of 47.5 degrees. This technique is simple, quick, and can be performed effectively on an out-patient basis. PMID- 1747311 TI - Trauma involving the proximal tibial epiphysis. AB - Thirty injuries involving the proximal tibial epiphysis were treated during a period of 28 years. The epiphysis was displaced in 16 cases (53%). Three patients presented with peripheral ischemia on admission, and one patient with associated ipsilateral femoral fracture developed delayed thrombosis of the popliteal artery. The treatment results were satisfactory in 21 of the 27 (74%) who were reassessed according to Shelton's evaluation criteria after an average post traumatic interval of 11.6 years. Three of the six patients with unsatisfactory outcome had a discrepancy in leg length of more than 2.5 cm after concomitant ipsilateral fracture of the femur or the tibia. One patient had a positive 3-cm anterior drawer sign, one patient had a 10 degree valgus deformity of the tibia, and one had to undergo above-knee-amputation because of delayed diagnosis of the vascular lesion. PMID- 1747312 TI - Biomechanical analysis of the dynamic hip screw in the treatment of intertrochanteric fractures. AB - A prospective study was performed in 148 elderly patients (over 60 years old) whose intertrochanteric fractures were caused by moderate trauma. The patients were treated with dynamic hip screws and followed up for at least 2 years (average 34 months). The lag screw was placed as the biomechanical analysis favored. Follow-up showed that the majority achieved good union and were without mechanical failure. The authors conclude that a lag screw should ideally be placed inferiorly toward the medial margin in the frontal plane and centrally in the sagittal plane. The length of the lag screw should be such as to extend from 1.0 cm beneath the subchondral bone to the lateral femoral cortex. At least four cortical screws (piercing the cortex at eight points) should be inserted on the distal femoral fragment. PMID- 1747313 TI - Venous air embolism during knee arthrography. A case report. AB - A 34-year-old man developed a nonfatal venous air embolism during arthrography of his post-traumatically contractured knee joint. From the arthrographic findings, injected air was assumed to have entered the great saphenous vein via the venous opening in the knee joint. Venous air embolism is an extremely rare complication of knee arthrography, but can occur. As it is potentially fatal, prompt recognition and appropriate positional and supportive therapy are essential. PMID- 1747314 TI - Bilateral stress fracture of the scaphoid. A case report. AB - Bilateral stress fractures of the scaphoid bones in a gymnast are reported and discussed with special consideration of the possible differential diagnoses; bipartite scaphoid and pseudarthrosis of the scaphoid bone. The relevance of the mechanical factors involved and the abduction and dorsiflexion of the wrist in gymnastics are suggested as likely pathomechanisms. PMID- 1747315 TI - Sports-related two-plane fractures of the distal tibia. Report of two cases. AB - Two cases of sports-related two-plane fractures of the distal tibia, their operative treatment and the result of therapy after hardware removal are reported. The incidence and mechanism of this type of fracture in adolescents are shown as well as the indication for surgical reconstruction depending on the gap in the joint surface of the distal tibia. PMID- 1747316 TI - Transplant continuing care nurse: a pilot project to integrate inpatient and ambulatory care settings. PMID- 1747317 TI - Peripheral vascular accesses: a 13-month study of clotting trends and survival. PMID- 1747318 TI - Hemolytic uremic syndrome (HUS): nursing experience at the Hospital for Sick Children, Toronto. PMID- 1747319 TI - Effectiveness of renal peer resource consultation. PMID- 1747320 TI - Noncompliance in chronic hemodialysis patients: an assessment approach for care planning. AB - Noncompliance is a nursing diagnosis frequently encountered by nephrology nurses in their practice. Patient assessment, as part of the nursing process, gives us insight into the numerous factors contributing to noncompliance. An assessment approach has been developed to assist nurses in acquiring the knowledge, empathy and understanding to plan effective care for the noncompliant patient. PMID- 1747321 TI - CAPD in Canada. PMID- 1747322 TI - Role of plasma exchange in renal disease. PMID- 1747323 TI - Heparin kinetics. PMID- 1747324 TI - [Hypothalamo-pituitary-adrenal function in liver cirrhosis of viral etiology]. AB - With the aim of evaluating the glucocorticoid function and the role of the adrenal gland in hypogonadism and feminization of cirrhotic patients, we examined 11 patients with virus-induced liver cirrhosis and 8 normal subjects as controls. In each subject serum levels of cortisol (C), progesterone (P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), delta 4 androstenedione (A), estrone (E1), testosterone (T), luteinizing hormone (LH) were assayed in basal conditions and after adrenocorticotropic hormone (ACTH) stimulation. Serum levels of ACTH, C, E1, estradiol (E2), T were assayed in basal condition and after dexamethasone suppression test. Moreover, a circadian study of ACTH, C and corticosteroid-binding globulin (CBG) was performed, with blood samples drawn at 8:00 and 20:00 on two consecutive days. Our results demonstrate that in cirrhosis: 1) normal levels of C, when metabolism is altered and CBG levels are reduced, are maintained by inhibition of ACTH secretion; 2) circadian rhythmicity of the pituitary-adrenal axis is well preserved; 3) in non-alcoholic cirrhosis, too, there is a reduction of androgens (T, DHEA, DHEAS, A) and a rise of estrogens (E2 and, more markedly, E1) and P; 4) in cirrhotic men E1 is mainly of adrenal origin and contributes, through negative feedback on LH secretion, to low levels of T. PMID- 1747325 TI - [Heart involvement in anorexia nervosa: an electrocardiographic, functional and morphological study]. AB - Mental anorexia (MA) is the most frequent condition of malnutrition in industrialized countries. Sudden death in MA is not infrequent. Furthermore, the role of nutritional state as an important determinant of myocardial function is known. Cardiovascular function was studied in 9 patients with MA. Blood electrolytes and thyroid function were assessed, basal and dynamic ECG, chest roentgenogram, M-mode echocardiography, ergometric test, cardiac output measurement and, in two cases, magnetic nuclear resonance (MNR) were performed. Our data confirm the ECG changes which were preeminent in the clinical context, as predictors of possible major, life-threatening arrhythmic events. The correct QT interval was normal in all patients. In 4 cases with heart rate less than 40 b/min, Holter ECG showed ventricular and atrial extrasystolic beats. In one case S-A blocks with idioventricular substitutive beats were recorded; the normal performance under maximal strain stands for a normal functional reserve. Blood electrolytes were in the normal range. The hypothalamic-pituitary axis can be considered as a cocausal factor by means of autonomic nervous system modulations. Echocardiography revealed only a mild reduction of ventricular wall thickness. Scattered degenerative myocardial involvement as shown by MNR imaging, could be the anatomical counterpart of a clinically emerging cardiomyopathy with potentially severe arrhythmias. PMID- 1747326 TI - [Immunogenetics: clinical and population aspects. The HLA system: clinical correlations. II. (3d of 5 parts)]. PMID- 1747327 TI - [Digitalis and heart failure]. AB - The authors first discuss the predominant cardiovascular mechanisms of the action of digitalis from a historical point of view. They then deal with different clinical situations in which the use of digitalis is limited, such as cardiac insufficiency resulting from altered diastolic function, although further studies dealing with the ratio of digitalis to diastolic function are necessary to gain a better insight into this problem. Finally, the discussion focuses on various clinical trials (including recent studies) on the use of digitalis in cardiac compensation in subjects with sinus rhythm. While the drug seems useless, if not risky in the majority of patients, in others with cardiomegaly, III tone and fluid overload the effects of the drug still seem beneficial at the clinical level. In this case, however, improved cardiac performance could not be demonstrated. The extra-inotropic types of digitalis action are thus reexamined, and some are correlated with favourable clinical effects which can be encountered in some forms of chronic heart failure. PMID- 1747328 TI - [Myxedematous coma due to transitory secondary hypothyroidism. Description of a case]. AB - Myxedema coma is a rare manifestation of hypothyroidism, and its prognosis is usually poor. We report a case of myxedema coma due to transient pituitary hypothyroidism with complete clinical and endocrinological recovery. The possible vascular origin of the syndrome is discussed. PMID- 1747329 TI - Association of the Budd-Chiari syndrome with lupus anticoagulant. Case report and critical review. AB - The Budd-Chiari syndrome (BCS) was diagnosed in a 30-year-old male hospitalized with hepatomegaly, abdominal collateral vessels and hepatic veins and inferior vena cava thrombosis (IVC) in 1988. The presence of circulating lupus anticoagulant (LAC) was suspected and demonstrated on this occasion in view of an earlier diagnosis of systemic lupus erythematosus (SLE) and recurrent vein thrombosis dating from 1981. There are sporadic reports of an association of BCS with SLE and other autoimmune diseases. The recent literature also describes associations with hypercoagulability due to LAC. These are reviewed together with the personal case to provide the rationale for correct diagnosis and therapy. PMID- 1747330 TI - Magnetic resonance imaging in the evaluation of congenital heart disease. AB - Magnetic resonance imaging is a powerful tool for studying patients with congenital heart disease. Its phenomenal contrast resolution, improved spatial resolution, and large field-of-view allow for graphic depiction of a wide array of congenital defects. Although this method was originally handicapped by the time it took to perform an exam and by poor image quality, advances in hardware and software coupled with attention to technique have led to a reliable diagnostic imaging modality. Although the technology is still evolving, it is not unreasonable to hope that the noninvasive imaging modalities of magnetic resonance and echocardiography will ultimately replace angiography in the evaluation of congenital heart disease. PMID- 1747331 TI - Magnetic resonance imaging in the diagnosis and evaluation of myocardial infarction. AB - Magnetic resonance (MR) imaging with the aid of MR contrast agents may be helpful to assess myocardial infarct size, the area at risk, and myocardial viability. MR contrast agents may also prove useful for evaluating myocardial perfusion with ultrafast MR imaging techniques. Dynamic cine MR imaging is an accurate method to assess regional myocardial dysfunction in ischemic heart disease. In addition, myocardial contraction can be determined by MR imaging under pharmacological stress or by direct tracking of wall motion with MR myocardial tagging. Combining the information from these MR imaging techniques provides a comprehensive evaluation of patients with coronary artery disease. PMID- 1747332 TI - Magnetic resonance approaches to the evaluation of pulmonary vascular anatomy and physiology. AB - MR imaging offers the potential for combined anatomic and flow-related information about the pulmonary circulation. Although conventional spin-echo sequences have provided an accurate and noninvasive means of evaluating the anatomy of the central pulmonary arteries and veins, newer MR techniques- including cine MR, velocity-encoded phase-contrast scans, spatial modulation of magnetization (SPAMM), fast scan techniques with breath-holding, and echo planar imaging in combination with computer-based post-processing--are providing physiological information superimposed on the anatomic maps. This paper reviews these new MR approaches to the integrated anatomic and physiologic imaging of the pulmonary vasculature. PMID- 1747333 TI - Medical records: a question of access. PMID- 1747334 TI - Shattered dreams. PMID- 1747335 TI - Pay and conditions: nurses' work and worth. PMID- 1747336 TI - Who should teach nurses? PMID- 1747337 TI - Health economics in psychiatric nursing. AB - The potential benefits to psychiatric nursing of the new science of health economics are explored in this article, which stems from more extensive research carried out by the authors. It is suggested that an analysis of the relationship between costs and clinical outcomes of community psychiatric nursing interventions will enable an objective ratification of the costs and benefits of treatment to emerge. The new discipline must be incorporated into evaluative research processes to allow psychiatric nursing to have an influence over future changes in health care provision. PMID- 1747338 TI - The process of continuing education. PMID- 1747339 TI - Non-steroidal anti-inflammatory drugs. PMID- 1747340 TI - Assessing the cost of nursing. PMID- 1747341 TI - Setting standards. PMID- 1747342 TI - Health promotion: head lice to heart disease. PMID- 1747343 TI - The meeting game. PMID- 1747344 TI - Ethics: professional accountability. PMID- 1747345 TI - Alternative therapy: complementary compliments. PMID- 1747346 TI - Practising nursing practice. PMID- 1747347 TI - Lateral thinking. Order from chaos. PMID- 1747348 TI - Lateral thinking. Thinking straight? PMID- 1747349 TI - Iatrogenic arterial injuries resulting from invasive procedures. AB - The many invasive arterial procedures that require cannulation of an artery with a large or traumatic catheter can be expected to produce iatrogenic injuries in a certain number of patients. While almost all arterial cannulation procedures are performed by physicians, nurses play a major role in performing baseline assessment of arterial blood flow, monitoring indwelling catheters, and detecting evidence of arterial injury. Clinical manifestations may appear during a procedure, while an indwelling arterial catheter is in place or after the catheter has been removed. Vigilant attention is essential to prevent serious injury or death due to a complication of an iatrogenic arterial injury. PMID- 1747350 TI - Commentary on carotid endarterectomy. PMID- 1747351 TI - Preoperative arteriogram revealed this "string" sign. PMID- 1747352 TI - Blue toe syndrome. AB - Taking a precise history from a patient who presents with a "bruised" toe in the absence of trauma requires sharp assessment skills and an investigative nature. Looking beyond the obvious in an otherwise healthy appearing individual calls for knowledge of many different disease processes including blue toe syndrome. Rapid identification, proper diagnosis, and correct medical and nursing management are essential for a positive outcome. PMID- 1747353 TI - Presidential address. PMID- 1747354 TI - Discharge planning for the vascular patient: where does home care fit in? PMID- 1747355 TI - Extracavitary vascular trauma. AB - Extracavitary vascular injuries involving the cervical area and the extremities constitute about 50% of all vascular injuries. Initial evaluation and resuscitation of patients with vascular injuries should follow standard Advanced Trauma Life Support protocols. Diagnosis of the injury is heavily reliant on physical examination, supplemented by arteriography in specific instances. Intraoperative management utilizes all the basic principles of vascular surgery. Postoperative nursing care focuses on the entire patient including the detection of early complications of vascular repair. Recent advances in transportation, resuscitation and operative techniques have lead to a decrease in mortality and morbidity. PMID- 1747356 TI - Esophageal atresia, tracheomalacia and arterial compression: role of aortopexy. AB - Between 1985 and 1990, we treated 46 cases of esophageal atresia in the pediatric surgery department in Marseille. In 17 of these patients atresia was associated with tracheomalacia. The most common respiratory manifestations were acute apneic attacks, cyanotic spells and recurring pneumopathy. The underlying cause was arterial compression of the airways by the innominate artery in 6 cases, the aortic arch in 2 cases, and a common origin of the innominate and left carotid arteries in 2 cases. Eleven patients underwent surgery to relieve arterial compression: suspension of the aorta from the under surface of the sternum (10 cases) and reimplantation of the innominate artery (1 case). Results in terms of tracheal caliber and symptomatic relief were excellent in 10 cases including 1 case requiring redo, and poor in 1 case. For diagnosis, our experience shows the importance of endoscopy, nuclear magnetic resonance and recognition of gastroesophageal reflux which is often associated (9/11). The role of tracheomalacia is discussed. On the basis of our results and those previously reported, aortopexy appears to be an effective surgical technique in patients with esophageal atresia presenting respiratory complications due to arterial compression. PMID- 1747357 TI - Clinical findings in middle lobe syndrome and other processes of pulmonary shrinkage in children (atelectasis syndrome). AB - Processes of atelectasis and pulmonary shrinkage are not confined to the right middle lobe. This fact is illustrated by case reports of five of our nine such patients. All cases shared common clinical and morphologic similarities: congenital malformations of the bronchial skeleton, compression, and chronic inflammation produce comparable pulmonary morphology that always includes atelectasis. Atelectasic processes of longer duration require surgical resection; this led to cures in all the authors' patients. PMID- 1747358 TI - Morbidity and mortality of short bowel syndrome in infancy and childhood. AB - This report concerns 59 infants and children with short bowel syndrome, most commonly caused by necrotizing enterocolitis in this study. Resection of atretic or gangrenous bowel was performed in 53 patients, tapering enteroplasty and primary anastomosis was performed in 13 patients, and temporary enterostomies were performed in 40 patients. Second-look laparotomy was useful in two of four cases of questionable bowel viability. The ileocecal valve was resected in 32 patients and remained intact in 27. The mean length of the remaining bowel was 58.4 cm. All patients received total parenteral nutrition and early enteral feedings. Home hyperalimentation was attempted when 50 per cent of the calorie intake was enteral. Intestinal adaptation required from 3 to 14 months. Frequent setbacks were related to catheter sepsis, rotavirus infection, carbohydrate intolerance, and liver dysfunction. The overall survival rate was 80 per cent with mortality due to sepsis associated with total parenteral nutrition and liver failure. PMID- 1747359 TI - Chronic recurrent appendicitis. A clinicopathologic study of 47 cases. AB - As part of a retrospective study 47 appendices from patients with a clinical and morphologic diagnosis of chronic recurrent appendicitis were studied by morphologic and immunohistochemical methods. Appendices with chronic recurrent appendicitis histologically show chronic active inflammation with increased numbers of immunocompetent cells, mostly T lymphocytes and subsequent scarring. In addition, there is an increase in the number of neural cells. Apparently the secretion of neurotropic inflammatory mediators, especially by activated and degranulating eosinophils, leads to a stimulation of nociceptive receptors and thus to the clinical symptoms. The diagnosis of recurrent chronic appendicitis is thus warranted in these cases not only clinically but also on the basis of histologic and immunohistochemical findings. PMID- 1747360 TI - High and intermediate imperforate anus: functional results and postoperative manometric assessment. AB - Between 1983 and 1989, 21 patients with high (12) and intermediate (9) imperforate anus were operated on according to the author's procedure. The anatomical results are satisfactory (20/21). The records of the clinical and paraclinical assessments of 13 of these patients with a follow-up of at least 5 years, is reported. The patient history demonstrates that 12 out of 13 are clean at night, with 1 to 3 bowel movements during the day. The intermediate forms have no accidental defecation and almost no soiling. Conversely, the high forms often soil but usually do not wear thick protections. Criteria of successful reconstruction as rectal examination, defecogram, CT scan or MRI, yield limited data but no formal conclusions. Manometric studies provide a better understanding of the bowel function after pull-through procedures, by studying the rectoanal inhibitory reflex threshold (RAIRT), the maximal anal resting closure (MARCP), the conscious rectal sensitivity threshold (CRST) and the maximal rectal compliance (MRC). Technical aspects of these recordings are detailed. Manometric recording from 13 of these 21 patients show that RAIRT is present in 3 out of 6 intermediate forms and 3 out of 7 high forms. CRST is normal in all the cases except 1. MARCP was normal in 5 out of 6 intermediate lesions and 5 out of 7 high lesions. MRC is good in 5 intermediate forms and 3 high forms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747361 TI - Single-stage correction of posterior hypospadias (178 cases). Comparison of three techniques: free skin graft, free bladder mucosal graft, transverse pedicle preputial graft. AB - Three techniques have been developed for single-stage repair of posterior hypospadias: free skin grafts, free bladder mucosal grafts, and pedicle preputial grafts. This multicenter retrospective study of 178 children who underwent surgery for posterior hypospadias was designed to compare the results achieved with these procedures. Free skin grafts (15 cases) resulted in the most frequent complications, and in particular the most severe strictures; in our opinion this technique should be abandoned. Pedicle preputial grafts (133 cases) gave the greatest number of successes from the outset, and should be preferred whenever the dimensions of the prepuce are sufficient for urethroplasty. Results with bladder mucosal grafts (30 cases) were not as good as with preputial grafts, but this technique remains the only solution when the meatus is in a very posterior position, and for children who have already undergone multiple operations. PMID- 1747362 TI - Importance of morphological findings in the progress and treatment of chest wall deformities with special reference to the value of computed tomography, echocardiography and stereophotogrammetry. AB - Patients with chest wall deformities have many particular anatomical, physiological, genetic, biomechanical and psychological characteristics. It is generally recognized that surgical correction of funnel chest and pigeon breast may be done for psychosocial reasons alone. Morphological and dynamic investigations are done to identify the function of the deformed chest wall and to permit objective assessment of the cosmetic and functional outcomes of the operation. There is no universally agreed standard for the diagnosis of funnel chest and pigeon breast. Non-invasive investigations, such as computed tomography (CT), echocardiography (ECG) and stereophotogrammetry (SP), improve the quality of the diagnostic assessment, including evaluation of its functional aspects, without directly influencing the decision to operate, which is still made mainly on subjective grounds. The value of these techniques in the diagnosis of chest wall deformities is assessed and the results of our personal experience are presented. PMID- 1747363 TI - Origin and treatment of fractures in spina bifida. AB - Children with spina bifida cystica have a high risk of fracturing their paraplegic legs. During the last fifteen years we observed 261 fractures and epiphyseal injuries in 173 children out of 1,400 (12.2%) patients with spina bifida. The increased risk of fracture seems to be due to reduced muscle activity in the paralysed limb with insufficient axial loading of the legs. A large proportion of fractures occurs after orthopedic interventions. Fractures are less common after urologic or neurosurgical procedures. Breaks are extremely frequent after operations in association with cast immobilization. Early standing and short immobilization times are the best defence mechanisms against fractures. If plasters are needed postoperatively one should preferably use the "Max and Moritz" standing cast. Fractures in spina bifida children heal quickly as compared to those in non-paralyzed children. In 30% excessive callus is seen. Immobilization for fracture care can be done in a standing cast even in the very early phase of treatment. In spite of the swelling and elevated temperature axial loading in the standing cast should continue. Splints and braces can be used instead of the plaster cast. By any means, the vicious circle of Fracture-Plaster Fracture-Plaster should be avoided. Repeated stress on the growth plate causes a mechanism of loosening. The most common site is the distal tibia and femur, less often loosenings occur in the proximal tibia and proximal femur. Epiphyseal loosening is a nosological entity seen in spina bifida and also in congenital absence of sensation. Distal tibial epiphyseal loosening is frequently seen in adolescents who have learned to walk only after muscle balancing procedures in the hips.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747364 TI - Uncommon torticollis in children. AB - We report on one case of uncommon torticollis in children caused by a pencil cap lodged in the neck. Diagnosis had been established two months after the trauma, during a screening for oro-pharyngeal cancer. The foreign body had pierced the posterior wall of pharynx without damaging the spine and large vessels. PMID- 1747365 TI - Gastric duplication communicating with an aberrant pancreas. AB - A case of gastric duplication in connection with an aberrant pancreas in a 14 months old boy is related. The non-specificity of signs and symptoms explains why the diagnosis of these lesions has been often mislead and usually made at laparotomy. Ultrasound and technetium scan could adequately characterize these anomalies pre-operatively. Simple excision is the treatment of choice. PMID- 1747366 TI - Renal oncocytoma in a child. AB - Oncocytoma is an exceptionally rare renal tumor in children. We report on one case of a twelve-year-old girl treated by nephrectomy. PMID- 1747367 TI - Identification of a ferryl intermediate of Escherichia coli cytochrome d terminal oxidase by resonance Raman spectroscopy. AB - The 680-nm-absorbing "peroxide state" of the Escherichia coli cytochrome d terminal oxidase complex, obtained by addition of excess hydrogen peroxide to the enzyme, is shown to be a ferryl intermediate in the catalytic cycle of the enzyme. This ferryl intermediate is also created by aerobic oxidation of the fully reduced enzyme. Resonance Raman spectra with 647.1-nm excitation show an FeIV = O stretching band at 815 cm-1, a higher frequency than noted in any other ferryl-containing enzyme to date. The band shows an 16O/18O frequency shift of 46 cm-1, larger than that observed for any porphyrin ferryl species. The FeIV = O formulation was unambiguously established by oxidations of the reduced enzyme with 16O2, 18O2, and 16O18O. Only the use of a mixed-isotope gas permitted discrimination between a ferryl and a peroxo structure. A catalytic cycle for the cytochrome d terminal oxidase complex is proposed, and possible reasons for the high v(Fe = O) frequency are discussed. PMID- 1747368 TI - Large-scale stable opening of supercoiled DNA in response to temperature and supercoiling in (A + T)-rich regions that promote low-salt cruciform extrusion. AB - We have studied the properties of (A + T)-rich sequences derived from ColE1 that promote cruciform extrusion at low ionic strength in supercoiled plasmids. We compared the chemical reactivity of the sequences in negatively supercoiled DNA (using osmium tetroxide and bromoacetaldehyde) with the results of two dimensional gel electrophoresis performed under the same conditions. Taken together, the results indicate the occurrence of cooperative helix-coil transitions in the (A + T)-rich DNA at low ionic strength, to form stable, denatured regions. The extent of the open region is a function of temperature and superhelix density, with an additional local destabilization brought about by the presence of cruciform structures. We present a simple statistical mechanical model of the helix-coil transition in the (A + T)-rich DNA, from which we have obtained estimates of the free energy for average base-pair opening of 0.31 kcal mol-1 and that for the formation of a helix-coil junction of 4.9 kcal mol-1, in 45 mM Tris-borate, pH 8.3, 0.5 mM EDTA. The results offer a model for the C-type mechanism of cruciform extrusion. Inverted repeats that are incorporated into the melted region undergo hairpin loop formation below 50 degrees C, and upon closure of the melted region, by reduction of temperature or increased ionic strength, they remain as a fully extruded cruciform structure. PMID- 1747369 TI - The mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysis. AB - We have used directly combined high-performance liquid chromatography-mass spectrometry (LC/MS) to examine the mechanism of the reaction catalyzed by the double-stranded RNA unwinding/modifying activity [Bass & Weintraub (1988) Cell 55, 1089-1098]. A double-stranded RNA substrate in which all adenosines were uniformly labeled with 13C was synthesized. An LC/MS analysis of the nucleoside products from the modified, labeled substrate confirmed that adenosine is modified to inosine during the unwinding/modifying reaction. Most importantly, we found that no carbons are exchanged during the reaction. By including H2(18)O in the reaction, we showed that water serves efficiently as the oxygen donor in vitro. These results are consistent with a hydrolytic deamination mechanism and rule out a base replacement mechanism. Although the double-stranded RNA unwinding/modifying activity appears to utilize a catalytic mechanism similar to that of adenosine deaminase, coformycin, a transition-state analogue, will not inhibit the unwinding/modifying activity. PMID- 1747370 TI - Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme. AB - To determine the energetic and structural consequences of placing a charged group within the core of a protein, two "buried charge" mutants, Met 102----Lys (M102K) and Leu 133----Asp (L133D) were constructed in phage T4 lysozyme. Both proteins fold at neutral pH, although they are substantially less stable than wild type. The activity of M102K is about 35% that of wild type, while that of L133D is about 4%. M102K could be crystallized, and its structure was determined at high resolution. The crystal structure (at pH 6.8) of the mutant is very similar to that of wild type except for the alpha-helix that includes residues 108-113. In wild-type lysozyme, one side of this helix is exposed to solvent and the other contacts Met 102. In the M102K structure this alpha-helix becomes much more mobile, possibly allowing partial access of Lys 102 to solvent. The stability of M102K, determined by monitoring the unfolding of the protein with CD, is pH dependent, consistent with the charged form of the substituted amino acid being more destabilizing than the uncharged form. The pKa of Lys 102 was estimated to be 6.5 both by differential titration and also by NMR analysis of isotopically labeled protein with 13C incorporated at the C epsilon position of all lysines. As the pH is lowered below pH 6.5, the overall three-dimensional structure of M102K at room temperature appears to be maintained to pH 3 or so, although there is evidence for some structural adjustment possibly allowing solvent accessibility to the protonated form of Lys 102. PMID- 1747371 TI - Alboaggregin-B: a new platelet agonist that binds to platelet membrane glycoprotein Ib. AB - A new protein, called alboaggregin-B (AL-B), has been isolated from Trimeresurus albolabris venom by ion-exchange chromatography. It agglutinated platelets without the need for Ca2+ or any other cofactor. The purified protein showed an apparent molecular mass on SDS-PAGE and gel filtration of about 23 kDa under nonreducing conditions. Ristocetin did not alter the binding of AL-B to platelets or affect AL-B-induced platelet agglutination. Agglutinating activity was not dependent on either proteolytic or lectin-like activity in AL-B. Binding analysis showed that AL-B bound to platelets with high affinity (Kd = 13.6 +/- 9.3 nM) at approximately 30,800 +/- 14,300 binding sites per platelet. AL-B inhibited the binding of labeled bovine von Willebrand factor (vWF) to platelets. Monoclonal antibodies against the 45-kDa N-terminal domain of platelet glycoprotein Ib inhibited the binding both of AL-B and of bovine vWF to platelets, and also inhibited platelet agglutination induced by AL-B and bovine vWF. Specific removal of the N-terminal domain of GPIb by treatment of the platelets with elastase or Serratia marcescens protease reduced the binding of labeled AL-B and bovine vWF to platelets and blocked platelet agglutination caused by both agonists. Monoclonal antibodies to glycoprotein IIb/IIIa, to bovine vWF, and to bovine serum albumin did not show any effect on the binding of AL-B to platelets. Our results indicate that the binding domain for AL-B on platelet GPIb is close to or identical with the one for vWF. This new protein may be a very useful tool for studying the interaction between platelets and vWF. PMID- 1747372 TI - Interaction of microtubule-associated proteins with microtubules: yeast lysyl- and valyl-tRNA synthetases and tau 218-235 synthetic peptide as model systems. AB - The respective contributions of electrostatic interaction and specific sequence recognition in the binding of microtubule-associated proteins (MAPs) to microtubules have been studied, using as models yeast valyl- and lysyl-tRNA synthetases (VRS, KRS) that carry an exposed basic N-terminal domain, and a synthetic peptide reproducing the sequence 218-235 on tau protein, known to be part of the microtubule-binding site of MAPs. VRS and KRS bind to microtubules with a KD in the 10(-6) M range, and tau 218-235 binds with a KD in the 10(-4) M range. Binding of KRS and tau 218-235 is accompanied by stabilization and bundling of microtubules, without the intervention of an extraneous bundling protein. tau 218-235 binds to microtubules with a stoichiometry of 2 mol/mol of assembled tubulin dimer in agreement with the proposed binding sequences alpha[430-441] and beta[422-434]. Binding stoichiometries of 2/alpha beta S tubulin and 1/alpha S beta S tubulin were observed following partial or complete removal of the tubulin C-terminal regions by subtilisin, which localizes the site of subtilisin cleavage upstream residue alpha-441 and downstream residue beta 434. Quantitative measurements show that binding of MAPs, KRS, VRS, and tau 218 235 is weakened but not abolished following subtilisin digestion of the C terminus of tubulin, indicating that the binding site of MAPs is not restricted to the extreme C-terminus of tubulin. PMID- 1747373 TI - Cytochalasin B interferes with conformational changes of the human erythrocyte glucose transporter induced by internal and external sugar binding. AB - To gain insight into the mechanism of facilitated sugar transport and possible mechanisms by which glucose transporter intrinsic activity might be altered, we have investigated conformational changes of the human erythrocyte glucose transporter induced by internal and external sugar binding and by the transporter inhibitor, cytochalasin B. Changes in the ability of thermolysin to digest glucose transporters present in erythrocyte ghosts were used to monitor conformational changes of the glucose transporter. The degree of protease digestion was determined by the amount of undigested glucose transporter remaining after the protease treatment, as assessed in Western blots using the glucose transporter specific monoclonal antibody 7F7.5. D-Glucose, the physiological substrate of the transporter, increased the transporter's susceptibility to cleavage by thermolysin. Nontransportable glucose analogues which bind specifically to either an internal or external glucose transporter sugar binding site also altered susceptibility of the transporter to thermolysin. Both methyl and propyl glucoside, which preferentially bind the internal sugar site, increased thermolysin susceptibility of the glucose transporter in a manner similar to that of D-glucose. In contrast, 4,6-O-ethylideneglucose, which preferentially binds the external sugar site, protected the transporter from thermolysin digestion. These results suggest that sugar binding to internal and external sugar sites induces distinct conformational changes and that the observed D-glucose effect on the susceptibility of the glucose transporter to thermolysin is due to D-glucose at equilibrium predominantly forming a complex with the internal sugar site. The protection from cleavage by thermolysin caused by external sugar binding is attenuated by the addition of an internally binding sugar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747374 TI - Development of affinity labeling agents based on nonsteroidal anti-inflammatory drugs: labeling of the nonsteroidal anti-inflammatory drug binding site of 3 alpha-hydroxysteroid dehydrogenase. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibiting the target enzyme cyclooxygenase (prostaglandin H2 synthase); however, little is known about the peptides comprising its NSAID binding site. Hydroxyprostaglandin dehydrogenases also bind NSAIDs, but their NSAID binding sites have not been well characterized. Using existing synthetic strategies, we have incorporated the bromoacetoxy affinity labeling moiety around the perimeter of two potent NSAIDs, indomethacin and mefenamate, a N-phenylanthranilate. The compounds synthesized were 1-(4-(bromoacetamido)benzyl)-5-methoxy-2-methylindole-3-acetic acid (1), 3 (2-(2-bromoacetoxy)ethyl)-1-(4-chlorobenzyl)-5-methoxy-2-methylindole (2), 4 (bromoacetamido)-N-(2,3-dimethylphenyl)anthranilic acid (3), N-(3 (bromoacetamido)phenyl)-anthranilic acid (4), and N-(4 (bromoacetamido)phenyl)anthranilic acid (5). To access whether these compounds have general utility in labeling NSAID binding sites, the compounds were evaluated as affinity labeling agents for 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) from rat liver cytosol. This enzyme displays 9-, 11-, and 15 hydroxyprostaglandin dehydrogenase activity, is inhibited potently by NSAIDs, and is homologous to bovine lung prostaglandin F synthase. Compounds 1-5 were shown to affinity label the NSAID binding site of 3 alpha-HSD. They inactivated 3 alpha HSD through an E.I complex in a time- and concentration-dependent manner with t1/2 values ranging from seconds to hours. Ligands that compete for the active site of 3 alpha-HSD (NAD+ and indomethacin) afforded protection against inactivation, and the inactivators could demonstrate competitive kinetics against 3 alpha-hydroxysteroid substrates by forming an E.NAD+.I complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747375 TI - Transport and metabolism of glucose in an insulin-secreting cell line, beta TC-1. AB - Kinetic characteristics of glucose transport and glucose phosphorylation were studied in the islet cell line beta TC-1 to explore the roles of these processes in determining the dependence of glucose metabolism and insulin secretion on external glucose. The predominant glucose transporter present was the rat brain/erythrocyte type (Glut1), as determined by RNA and immunoblot analysis. The liver/islet glucose transporter (Glut2) RNA was not detected. The functional parameters of zero-trans glucose entry were Km = 9.5 +/- 2 mM and Vmax = 15.2 +/- 2 nmol min-1 (microL of cell water)-1. Phosphorylation kinetics of two hexokinase activities were characterized in situ. A low-Km (0.036 mM) hexokinase with a Vmax of 0.40 nmol min-1 (microL of cell water)-1 was present along with a high-Km (10 mM) hexokinase, which appeared to conform to a cooperative model with a Hill coefficient of about 1.4 and a Vmax of 0.3 nmol min-1 (microL of cell water)-1. Intracellular glucose at steady state was about 80% of the extracellular glucose from 3 to 15 mM, and transport did not limit metabolism in this range. In this static (nonperifusion) system, 2-3 times more immunoreactive insulin was secreted into the medium at 15 mM glucose than at 3 mM. The dependence of insulin secretion on external glucose roughly paralleled the dependence of glucose metabolism on external glucose. Simulations with a model demonstrated the degree to which changes in transport activity would affect intracellular glucose levels and the rate of the high-Km hexokinase (with the potential to affect insulin release). PMID- 1747376 TI - Analysis of hydride transfer and cofactor fluorescence decay in mutants of dihydrofolate reductase: possible evidence for participation of enzyme molecular motions in catalysis. AB - A remarkable correlation has been discovered between fluorescence lifetimes of bound NADPH and rates of hydride transfer among mutants of dihydrofolate reductase (DHFR) from Escherichia coli. Rates of hydride transfer from NADPH to dihydrofolate change by a factor of 1,000 for the series of mutant enzymes. Since binding constants for the initial complex between coenzyme and DHFR change by only a factor of 10, the major portion of the change in hydride transfer must be attributed to losses in transition-state stabilization. The time course of fluorescence decay for NADPH bound to DHFR is biphasic. Lifetimes ranging from 0.3 to 0.5 ns are attributed to a solvent-exposed dihydronicotinamide conformation of bound coenzyme which is presumably not active in catalysis, while decay times (tau 2) in the range of 1.3 to 2.3 ns are assigned to a more tightly bound species of NADPH in which dihydronicotinamide is sequestered from solvent. It is this slower component that is of interest. Ternary complexes with three different inhibitors, methotrexate, 5-deazafolate, and trimethoprim, were investigated, along with the holoenzyme complex; 3-acetylNADPH was also investigated. Fluorescence polarization decay, excitation polarization spectra, the temperature variation of fluorescence lifetimes, fluorescence amplitudes, and wavelength of absorbance maxima were measured. We suggest that dynamic quenching or internal conversion promotes decay of the excited state in NADPH-DHFR. When rates of hydride transfer are plotted against the fluorescence lifetime (tau 2) of tightly bound NADPH, an unusual correlation is observed. The fluorescence lifetime becomes longer as the rate of catalysis decreases for most mutants studied. However, the fluorescence lifetime is unchanged for those mutations that principally alter the binding of dihydrofolate while leaving most dihydronicotinamide interactions relatively undisturbed. The data are interpreted in terms of possible dynamic motions of a flexible loop region in DHFR which closes over both substrate and coenzyme binding sites. These motions could lead to faster rates of fluorescence decay in holoenzyme complexes and, when correlated over time, may be involved in other motions which give rise to enhanced rates of catalysis in DHFR. PMID- 1747377 TI - Kinetics of extension of O6-methylguanine paired with cytosine or thymine in defined oligonucleotide sequences. AB - The frequency of extending m6G.C or m6G.T pairs, when the 3' and 5' flanking neighbors of m6G are either cytosines or thymines, was investigated using primed 25-base-long oligonucleotides and the Klenow fragment of Escherichia coli DNA polymerase I (Kf). The efficiency, Vmax/Km, of extension to the following normal base pair was up to 40-fold greater than for the formation of the m6G.T or m6G.C pair. The frequencies of inserting either dCMP or dTMP opposite these m6G bases did not appear to be different in the two sequences, C-m6G-C and T-m6G-T, but extension was favored in the C-m6G-C sequence. The m6G.T pair extended to a C.G pair most efficiently, indicating that it was not a strong block to continued replication past the template lesion. Thus, m6G.T flanked by cytosines replicates more readily than when flanked by thymines, increasing G----A transitions. These data lend further support to the importance of sequence context in mutagenesis. PMID- 1747378 TI - What educational requirements for a nursing executive? AB - A review of the literature, interviews with nursing executives in community and tertiary care facilities, and consideration of courses at one Canadian university are the basis for the development of a sample graduate level nursing program with an administration major. Course inclusion was predicated by the defined roles of practising nursing executives. Future trends in health care were considered as they affect needs for programming. PMID- 1747379 TI - Interviewing for a deanship in nursing--an informed process. AB - This article has been written to assist those individuals who aspire to administration in nursing education. Being interviewed for a Deanship is an exacting experience during which the candidate must make an impression, as well as, collect enough data upon which an informed decision can be made. Good preparation for the process is essential. Data is gathered about the School, the people in the School (faculty, students and staff), the position (and the University and the professional community), as well as, the community. No one School of Nursing is perfect but the informed candidate will be more able to decide which risks are worth taking. PMID- 1747380 TI - The staff nurse employment interview selection process: judgment and decision errors and how to avoid them. Part I. AB - The employee interview is a complex decision-making process which has a potential effect on the future of the organization. It is in the organization's best interest to ensure that the interview process results in the selection of candidates who most clearly meet predetermined selection criteria. Reliable and valid interviews improve the probability of selecting candidates who are most likely to succeed. A review of employment interview literature is discussed relating to judgement and decision errors, and the reliability and validity of the employment interview. Part II will review the development of a semistructured, employment interview questionnaire which was based on College of Nurses of Ontario Standards of Practice (1984) and staff nurse position description. PMID- 1747381 TI - The staff nurse employment interview: predicting performance outcomes. Part II. AB - The Employment Standards Act of Ontario and Labour Relations policy in health care organizations require that employment decisions be based on the comparative level of knowledge, skills, abilities, and experience of job applicants. Reliable and valid employment interviews guide employers in that process. A semistructured staff nurse employment interview tool was developed and tested for reliability and validity (content and predictive) on a medical unit in an acute-care hospital setting. Of 25 interview questions evaluated as having content validity based on comparison with the job analysis and Standards of Practice, five (holistic care, assessments of patient's ability to cope, teaching, collaboration, and problem solving) were identified as having statistically significant relationships with performance outcomes evaluated one year after the initial interview. Total interview test scores were predictive of overall competency in job performance. Those questions evaluated as content valid and as attaining predictive validity were used as the basis for the development of a structured staff nurse employment interview questionnaire. PMID- 1747382 TI - A barometer for nursing education: the health of Canadian universities. PMID- 1747383 TI - The head nurse: perceptions of stress and ways of coping. AB - Head nurses occupy an important position in hospitals, but there have been few studies of the stress experienced by these first line managers. The purpose of this research was to investigate patterns and sources of workplace stress and how head nurses coped with it. Twenty-one head nurses from four teaching hospitals were interviewed. Major sources of stress were lack of resources including nursing staff, work load and powerlessness. Events were seen as stressful because the head nurse lacked control or did not feel competent. Length of time in position affected perceptions of stress. Coping with stress was generally through problem-focused strategies. The findings may reflect the impact of role changes on head nurses. PMID- 1747384 TI - Cholesterol-induced alteration of apolipoprotein A-I conformation in reassembled high density lipoprotein. AB - Recent reports have shown that apolipoprotein A-I (apo A-I), the major protein of high density lipoprotein (HDL) may exist in different conformational states. We studied the effects of apolipoprotein A-II and/or cholesterol on the conformation of apo A-I in reassembled HDL. Analysis of tryptophan fluorescence quenching in the presence of iodine suggested that cholesterol increased the number of apo A-I tryptophan residues accessible to the aqueous phase, but decreased their mean degree of hydration. These observations cannot be totally explained on the basis of the effect of cholesterol on phospholipid viscosity as determined by fluorescence anisotropy of diphenyl hexatriene. We did not observe any effect of apo A-II on the conformation of apo A-I. PMID- 1747385 TI - Characterization of an osmoregulated periplasmic glycine betaine-binding protein in Azospirillum brasilense sp7. AB - Azospirillum brasilense is able to use glycine betaine as a powerful osmoprotectant; the uptake of this compound is strongly stimulated by salt stress, but significantly reduced by cold osmotic shock. Non-denaturing PAGE in the presence of [methyl-14C] glycine betaine and autoradiography demonstrated the presence of one glycine betaine-binding protein (GBBP) in periplasmic shock fluid obtained from high-osmolarity-grown cells. The binding activity was absent in periplasmic fractions from cells grown at low osmolarity. SDS-PAGE analysis showed that the osmotically inducible GBBP has an apparent molecular weight of 32,000. The isoelectric point was between 5.9 and 6.6, as determined by isoelectric focusing. This protein bound glycine betaine with high affinity (KD of 3 microM), but had no affinity for either other betaines (proline betaine, gamma-butyrobetaine, pipecolate betaine, trigonelline, homarine) or related compounds (choline, glycine betaine aldehyde, glycine and proline). Optimum binding activity occurred at pH 7.0 to 7.5, and was not altered whether or not the binding assays were done at low or high osmolarity. Immunoprecipitation and Western blotting showed that immunoadsorbed anti-GBBP antibody from E coli cross reacted with the GBBP produced by A brasilense cells grown at high osmolarity. PMID- 1747386 TI - Kinetic properties of normal human erythrocyte glucose-6-phosphate dehydrogenase dimers. AB - The steady-state kinetics of normal human erythrocyte glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ oxidoreductase, EC 1.1.1.49) dimers were studied as a function of pH and temperature. Inhibition studies using glucosamine 6-phosphate, NADPH and p-hydroxymercuribenzoate (P-OHMB) were also carried out at pH 8.0. The existence of two binding sites on the enzyme with a transition from low to high affinity for NADP+ when NADP+ concentration is increased is indicated by the nonlinear Lineweaver-Burk plots and sigmoid kinetic patterns. NADPH inhibition was found to be competitive with respect to NADP+ and non-competitive with respect to glucose-6-phosphate. Logarithmic plot of Vmax against pH and inactivation by P-OHMB indicate the participation in the reaction mechanism of imidazolium group of histidine and sulhydryl groups. The initial velocity and product inhibition data gave results which are consistent with the dimeric enzyme following an ordered sequential mechanism. A possible random mechanism is ruled out by the inhibition results of glucosamine 6-phosphate. PMID- 1747387 TI - Mechanogenetic regulation of transcription. AB - In many biological systems mechanical forces regulate gene expression: in bacteria changes in turgor pressure cause a deformation of the membrane and induce the expression of osmoregulatory genes; in plants gravity regulates cell growth ('geotropism'); in mammals stretching a muscle induces hypertrophy which is accompanied by qualitative changes in protein synthesis. Consequently, the term 'mechanogenetic control' seems to be a suitable common name for all these processes. The mechanism by which mechanical factors modulate transcriptional activity is still unknown. The purpose of this review is to bring together data from different fields in order to obtain a better understanding of the mechanogenetic control of cell growth. PMID- 1747388 TI - Structure and biological activity of crustacean gastrointestinal peptides identified with antibodies to gastrin/cholecystokinin. AB - Four gastrin/cholecystokinin-like peptides (G/CCK) which cross-react with a specific C-terminal gastrin/CCK antiserum have been isolated from the stomach of the marine crustacean Nephrops norvegicus. The molecular weight of the four peptides was estimated between 1000 and 2000 Da by molecular sieving. By radioimmunoassay, the cross-reactivity of these peptides with human gastrin 17-I was found to be around 0.03%. Pure peptidic fractions were recovered after four successive steps of HPLC. Amino-acid analysis suggested a similarity between the four peptides identified which may belong to a new family. A limited homology between the C-terminus of one Nephrops peptide and vertebrate G/CCK was found after sequencing. Two of the peptides exhibited secretagogue effects on crustacean isolated midgut glands. The Nephrops peptides, although structurally distinct from the vertebrate G/CCKs, appear to serve similar biological functions in crustaceans. PMID- 1747389 TI - The initiation codon AUG binds at a hydrophobic site on yeast 40S ribosomal subunits as revealed by fluorescence studies with bis (1,8 anilinonaphthalenesulfonate). AB - Binding studies of yeast 40S ribosome with bis (1,8-anilinonaphthalenesulfonate) (bis-ANS) revealed the binding of 3-4 molecules of bis-ANS per ribosome with a dissociation constant (Kd) of 1.45 microM. Binding of AUG to the 40S subunits resulted in a concentration-dependent decrease in the bis-ANS fluorescence without displacing all of the bound bis-ANS from the ribosomes. The residual bis ANS fluorescence at saturation with AUG corresponds to about 3 molecules of bis ANS per ribosome. Thus AUG displaces one of the bound bis-ANS molecules. The data suggest that AUG binds at a hydrophobic site on the yeast 40S subunit. PMID- 1747390 TI - Purification and characterization of a germ cell-specific form of elongation factor 1 alpha (EF-1 alpha) from Xenopus laevis. AB - Elongation factor 1 alpha (EF-1 alpha) was purified to homogeneity from full grown oocytes of Xenopus laevis. This protein is encoded by a gene previously shown to be expressed in male and female germ cells, and repressed in somatic cells. The purified protein was identified with EF-1 alpha on criteria of molecular mass, cross-reaction with antibodies raised against Artemia salina EF-1 alpha, affinity for guanine nucleotides, and ability to promote the mRNA dependent binding of aminoacyl tRNA to 80S ribosomes. PMID- 1747391 TI - Pineal gland transplants into the cerebral hemisphere of newborn rats: a study of the blood brain barrier and innervation. AB - Pineal glands from neonatal (0-1 day) Long-Evans black-hooded rats were transplanted into the cerebral hemispheres of litter mates for periods of 1 to 5.5 months. Grafts exhibited differentiated pinealocytes that were intensely immunoreactive for serotonin. Transplant vasculature was permeable to endogenous IgG, comprised fenestrated endothelia with wide pericapillary spaces typical of in situ glands, and had a volume density intermediate to that of surrounding cortex and in situ pineals. Along the periphery, transplant capillaries tended to have continuous endothelia similar to those of host cortex. This peripheral zone was impermeable to endogenous IgG and appeared to increase in size in older grafts. The presence of noradrenergic-like fibers within the perivascular compartment suggested that transplants were innervated by peripheral sympathetic neurons from the superior cervical ganglia. In animals which had been superior cervical ganglionectomized, noradrenergic-like fibers were absent or degenerating. Neural regulation of transplant metabolic activity was suggested by the increased frequency of pinealocyte synaptic ribbons in denervated grafts. These findings are consistent with the hypothesis that factors from both graft and host influence vasculature physiology and differentiation in neural transplants. Furthermore, grafts appeared to receive appropriate neural input from the peripheral sympathetic system. PMID- 1747392 TI - Electrophysiological and morphological properties of embryonic neocortical grafts developing in different regions of the host rat brain. AB - Parallel morphological and electrophysiological studies of embryonic neocortical tissue (primordia of anterior parietal--presumptive sensorimotor--cortex) grafted into different regions of the host adult brain (sensori-motor cortex, caudate putamen, septum or thalamus) were carried out to investigate to what extent the properties of transplanted embryonic neocortex--an advanced organizational form of neuronal tissue--are affected by homotopic or heterotopic surroundings. The results point to the importance of the host tissue environment as it influences both the size, the morphological and functional properties of the implanted embryonic cortical plate tissue. The cortical grafts were smaller in size when developed homo-topically in sensorimotor cortex and grew larger in heterotopic environment (caudate-putamen, septum, thalamus). The orientation of neuronal dendrites in the grafts tends to follow that seen in the surroundings. The homotopic grafts showed a better structural integration into the host brain. Differences were seen between intracortical and subcortical transplants in the spontaneous firing rate of neurons and in the ratio of units with various types of spontaneous discharge. PMID- 1747393 TI - Intraocular retinal transplantation: a review. AB - This review covers intraocular transplantation of retinal tissue. This has importance both for theoretical understanding of retinal and neural development and for possible future clinical application. Transplantation sites have ranged from the anterior chamber through the retina to the subretinal space. Transplanted tissue has ranged from whole retina to specific retinal layers or specific types of retinal cells. Both within-species and inter-species transplants have been performed, and donor age has ranged from embryonic to adult. The ability of transplanted tissue to be accepted and to differentiate in host eyes has been studied. The conditions under which successful transplants are obtained, host-graft interactions, and transplantation methodologies have been explored. Morphological, and to a small extent, also functional characteristics of the transplants have been studied. PMID- 1747394 TI - Survival and synapse formation of transplanted rat rods. AB - Isolated rods enzymatically removed from normal adult rat retina have been transplanted to the subretinal space of adult rats with a retinal dystrophy which has destroyed almost all the photoreceptors. These transplanted rods survive for months after transplantation during which time they form synapses with other retinal cells. Rod spherules with large amounts of synaptic vesicles and synaptic ribbons are found forming discreet contacts with pre- and post-synaptic densities in arrangements closely resembling those seen in the normal retina. PMID- 1747395 TI - A comprehensive method validation strategy for bioanalytical applications in the pharmaceutical industry--2. Statistical analyses. AB - The first paper in this two-part series described [Lang and Bolton, J. Pharm. Biomed. Anal. 9, 357-361 (1991)] an overall validation strategy for bioanalytical methods. This second paper focuses on the statistical analyses performed on the validation data that will allow the analyst to evaluate the reliability and reproducibility of a bioanalytical method. Based on the validation results, acceptance criteria for the quality control concentrations are established and used during the study proper to determine if the analytical run is valid. After analysing the clinical study samples and accepting the analytical runs, the quality control results are incorporated into databases to update their acceptance limits. This continuous validation process enables the analyst to monitor the method's performance over time and be confident that accurate sample concentrations are being reported. It is important to emphasize that the statistical analyses of the data provide information that should be considered from a practical point of view by the analyst. The analyst should use sound judgement in evaluating the reliability of the method. PMID- 1747396 TI - Photostability testing of drug substances and drug products in UK pharmaceutical laboratories. AB - Results of a survey on photostability testing of drug substances and products by UK pharmaceutical laboratories are presented. The results indicate diverse practices in the form of presentation of the product and particularly in exposure to light (as measured in lx days), although there was more consistency in analytical methods and in the analytical criteria used to classify products as stable or unstable for those laboratories adopting this type of classification. A majority of laboratories use daylight in addition to artificial light sources for tests on drug substances and products. Artificial daylight fluorescent tubes and xenon lamps are the most widely used sources of artificial light and both should provide a reasonable simulation of natural light. All laboratories intend their photostability tests to represent light exposure which exceeds that expected to occur in practice but the tests actually applied vary widely in severity as shown in the wide range in light exposure (8-4500 klx days). Therefore the classification of products as stable or unstable needs to be considered carefully in relation to the severity of the test used. Testing procedures for drug substances are broadly similar to those used for drug products. It is concluded that the variation in testing procedure is the result of differing perceptions regarding product exposure in practical usage and the absence of regulatory guidelines. PMID- 1747397 TI - Solubility and acid-base behaviour of midazolam in media of different pH, studied by ultraviolet spectrophotometry with multicomponent software. AB - The solubility of midazolam is less than 0.1 mg ml-1 at neutral pH and it increases considerably in acidic media. A pKa value of 6.04 at 24 +/- 1 degree C was calculated from the solubility data. In acidic media midazolam is reversibly converted to the corresponding benzophenone (open-ring form). The extent of this reaction was investigated by assaying the two compounds simultaneously by UV spectrophotometry with multicomponent software. The structure of the benzophenone derivative was verified by IR, MS and 1H and 13C NMR spectrometry. PMID- 1747398 TI - Synthesis and identification of pilocarpic acid diesters, prodrugs of pilocarpine. AB - A series of new pilocarpic acid diesters were synthesized to obtain prodrugs for pilocarpine with varying physico-chemical properties. Thermospray liquid chromatography-mass spectrometry (TSP-LC-MS), liquid chromatography with UV detection (LC-UV) and NMR-spectroscopy were used for the identification of the synthetic products and for evaluation of their purity including typical impurities (pilocarpic acid monoester, pilocarpine). TSP-LC-MS-analysis was performed in the reversed-phase mode using acetonitrile (60%)-0.2 M ammonium acetate (40%) as mobile phase. In LC-UV-analysis chromatographic separation was carried out on a reversed-phase column and the mobile phase consisted of methanol (71%) and 0.02 M potassium dihydrogen phosphate, pH 4.5 (29%). Electron ionization-mass spectrometry (EI-MS) was used for elucidation of structures. Elemental compositions of the substances were verified with high resolution-mass spectrometry (HR-MS). The complete establishment of structures presented was based on 1H-, and COSY-NMR-spectroscopy joined to TSP-LC-MS-analysis. PMID- 1747399 TI - Use of normal-phase microcolumn high-performance liquid chromatography for the study of hydrolytic stability, metabolic profiling and pharmacokinetics of an antiepileptic drug, benzonal. AB - A normal-phase microcolumn HPLC method is proposed for the quantitative determination of the most frequently used antiepileptic drugs and some compounds developed recently. The main advantage of this method, in comparison with other micro-scale HPLC techniques for antiepileptic drugs, is that it is used under isocratic conditions at room temperature (22 degrees C). The hydrolytic stability of benzonal (BZ) has been studied using this method together with mass spectrometry (MS), and IR, UV and NMR spectroscopy. Three pathways of hydrolytic degradation were established in alkaline conditions, whereas in an acid medium only one of these routes was followed. An investigation of the metabolic profiling of BZ in guinea-pigs showed that the drug undergoes fast hydrolysis in the intestinal tract forming phenobarbitone (PB) and benzoic acid (BA). Only PB was detected in brain tissue and it is probably responsible for the whole therapeutic effect. The pharmacokinetic parameters of this metabolite (PB) were determined in guinea-pigs, and their identity with the pharmacokinetic parameters of PB as the parent drug was confirmed. PMID- 1747400 TI - Analysis of nifedipine and its pyridine metabolite dehydronifedipine in blood and plasma: review and improved high-performance liquid chromatographic methodology. AB - A reversed-phase HPLC method is described for the simultaneous determination of nifedipine and its primary pyridine metabolite dehydronifedipine in blood and plasma, that involves UV detection and neutral (blood) or alkaline (plasma) extraction. The limit of reliable determination is found to be 3 ng ml-1 with an inter-assay RSD of below 11%. In the presence of haemoglobin, nifedipine is unstable at pH greater than 10, necessitating neutral extraction for the measurement of nifedipine in haemolysed blood. Published methods for analysis of nifedipine are reviewed, emphasizing the lack of specificity and sensitivity which render many of them unsuitable for the investigation of nifedipine disposition in man. PMID- 1747401 TI - Determination of clenbuterol in urine of calves by high-performance liquid chromatography with in series ultraviolet and electrochemical detection. AB - A method for the determination of clenbuterol in calf urine is described. After a simple two-step sample pretreatment, involving an Extrelut-3 column and a solid phase extraction column (C2), the separation of clenbuterol from interfering compounds present in urine samples was performed with ion-pair chromatography on a LiChrospher RP-Select-B column with a mixture of acetonitrile and sodium dodecyl sulphate/acetate buffer (pH 3.5) as mobile phase. To obtain a higher specificity, two different physico-chemical detection techniques, i.e. UV absorption (244 nm) and electrochemical detection (+1250 mV), were applied in series. The lowest limit of determination was 0.5 ng ml-1 and the mean recovery of clenbuterol spiked at 10 ng ml-1 level was 79.9% (RSD = 6.3%; n = 9). The analysis of one urine sample, including sample preparation, took less than 2 h. Results obtained with this method correlated well with GC-MS analysis. With the described method about 400 urine samples were analysed. In a pilot experiment, in which a calf received orally 4 micrograms clenbuterol.HCl per kilogram body weight twice a day (five times the therapeutic dose for oral application) for 5 days, the highest concentration of clenbuterol found in urine was 73 ng ml-1. In a second experiment, in which two calves received the therapeutic dose of clenbuterol.HCl twice a day over a period of 2 weeks, the highest concentration of clenbuterol was 75 ng ml-1 of urine. Eight days after the final application, concentrations of clenbuterol were lower than 0.5 ng ml-1. From this excretion study for clenbuterol a half-life value of approximately 1.5 days was calculated. PMID- 1747402 TI - Derivatized beta-cyclodextrins combined with high field NMR for enantiomer analysis: application to ICI 185,282 (5(Z)-7- ([2RS,4RS,5SR]-4-o-hydroxyphenyl-2 trifluoromethyl-1,3-dioxan-5-yl) heptenoic acid). PMID- 1747403 TI - Stability of adrenaline pH-adjusted solutions of local anaesthetics. PMID- 1747404 TI - The determination of 2,6-diisopropylphenol (propofol) in an oil in water emulsion dosage form by high-performance liquid chromatography and by second derivative UV spectroscopy. PMID- 1747405 TI - Rapid simultaneous determination of trimethoprim, sulphamethoxazole and acetylsulphamethoxazole in human plasma and urine by high-performance liquid chromatography. PMID- 1747406 TI - Determination of (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2- yl] 2,2-dimethylpropanoic acid), a novel leukotriene biosynthesis inhibitor, in human plasma and urine by liquid chromatography. PMID- 1747407 TI - [Analysis of the structure of prolactin terminal fragments as potential substrates of serine and proline-specific proteinases]. AB - The biochemical mechanism of action of prolactin is unknown. This hormone enters the blood stream and binds to receptors predominantly in the monomeric form. A structural analysis of mammalian and piscine prolactin based on the present-day concepts of proteolytic processing of the hormone molecules in target tissues has been carried out. The experimental data suggest that prolactin molecules are protected from exopeptidase influence by their terminal cyclic peptides. The highly conservative proline-2 residues increase the resistance of the mammalian hormone N-terminal fragment to the effects of many aminopeptidases. Structurally the C-terminal cyclic peptides of prolactin, growth hormone and placental lactogen were shown to be homologous to peptides inhibiting trypsin-like proteinases. A structural analysis of the N-terminal domain of mammalian prolactin revealed the important role of Pro-2 and Pro-4 residues at positions adjacent with and inside the disulfide moiety. It is assumed that these proline residues and the cyclic structure are necessary for the manifestation of the inhibiting effect of the mammalian prolactin N-terminal dodecapeptide on proline specific proteinases. It is assumed that proteolytic degradation of prolactin molecules in target tissues may induce the secretion of functionally active peptides. PMID- 1747408 TI - [Inhibition of Fc-receptor dependent platelet aggregation by monoclonal antibodies against the glycoprotein IIb-IIIa complex]. AB - A murine monoclonal antibody (MoAb) VM16a specifically binding to human platelets has been produced. Approximately 56,000 molecules of VM16a bound per platelet at saturation (Kd = 7.9 nM) but no binding to platelets from Glanzmann's thrombasthenia patients was detected. VM16a precipitated two proteins with molecular masses corresponding to those of glycoproteins (GP) IIb and IIIa from solubilized surface-labelled platelets. However, after dissociation of the GPIIb- IIIa complex with EDTA VM16a did not bind to platelets and precipitated nothing from their lysate, thus evidencing that its determinant is complex-dependent. VM16a had no effect on ADP-, thrombin- and ristocetin-induced platelet aggregation but inhibited the aggregation induced by collagen. This inhibitory effect was more pronounced in the presence of plasma. VM16a completely blocked the Fc-receptor-mediated aggregation induced by aggregated human IgG, aggregated murine IgG1 and the previously described MoAb VM58. F(ab')2 fragments of VM16a were also able to inhibit this aggregation by decreasing the rate of aggregation induced by aggregated IgG and by extending the lag phase of VM58-induced aggregation. These results suggest that the platelet Fc-receptor may be topographically associated with the GPIIb-IIIa complex. PMID- 1747409 TI - [Substrate specificity of T4 RNA-ligase. The role of phosphate nucleotide residues in the formation of a covalent AMP-RNA-ligase complex]. AB - The inhibiting effect of adenosine, AMP, ADP, ATP, gamma-thio ATP (I), beta,gamma imine ATP (II), beta,gamma-methylene ATP (III), P1,P3-di(adenosine-5') triphosphate (IV), P1,P4-di(adenosine-5') tetraphosphate (V) and adenosine 5' tetraphosphate (VI) on the first step of the T4 RNA ligase reaction was studied. All the compounds tested, with the exception of adenosine, appeared to be competitive inhibitors of the first step of the enzymatic reaction. The inhibition constants (Ki) for the ATP analogs were determined. The data obtained suggest that the efficiency of inhibition depends on the number of phosphate groups and on the structure of ATP analogs. All the compounds under study (I-VI), except for AMP and ADP, form covalent AMP-RNA ligase complexes. PMID- 1747410 TI - [Metabolism of cholesterol esters in cultured macrophages under the action of the calcium antagonists verapamil and nifedipine]. AB - Using mouse macrophage cultures, the effects of verapamil and nifedipine on cholesterol ester metabolism were studied with special reference to the following parameters: i) incorporation of 14C-oleate into cholesterol esters (ChE), ii) contents of common and free cholesterol (FCh), iii) removal of 14C-oleate from ChE and incorporation of 3H-FCh into ChE and, iiii) excretion of 3H-Ch from the cells. Verapamil and nifedipine (10-100 microM) decreased the incorporation of 14C-oleate into ChE, increased the concentration of FCh but had no appreciable effect on the concentration of common Ch in macrophages cultured in the presence of acetylated low density lipoproteins. The drugs stimulated the removal of 14C oleate from cellular ChE. The pharmacological concentrations (25-75 microM) of verapamil and nifedipine increased the excretion of 3H-Ch from ChE of macrophages in the presence of serum and high density lipoproteins. The results obtained suggest that verapamil and nifedipine mediate the antiatherosclerotic effect via reduction of intracellular synthesis of ChE, stimulation of ChE hydrolysis and cholesterol excretion from the cells. PMID- 1747411 TI - [Interconnection between the structure and protective action of normal and pathological ceruloplasmin preparations in copper-induced erythrocyte lysis]. AB - It was found that the differences in the protective effects of ceruloplasmin (CP) isolated from the blood of healthy donors and of the ceruloplasmin-like protein (pat-CP) isolated from the blood of patients with hepatovertebral dystrophy (HCD) during Ca(2+)-induced lysis of erythrocytes (RBC) result from significant changes in the carbohydrate fragment of pat-CP, the bulk of which (65%) is devoid of mannose and acetylglucosamine residues. According to the data from lentil-lectin Sepharose chromatography, only 4% of pat-CP molecules contain the [formula; see text] fragment necessary for the binding to ER receptors. The curves reflecting the Cu2+ accumulation in healthy donor ER and in pat-CP during the Cu(2+)-induced lysis were found to differ significantly. The ability of pat-CP to prevent the accumulation of Cu2+ in ER and pat-ER was markedly decreased compared with CP. Besides, CP prevented the diminution of reduced glutathione (GSH) in ER in a greater degree than pat-CP, whereas pat-ER, in contrast with CP, had no effect on the GSH concentration in pat-ER. It is suggested that the reactions occurring in the cell during Cu(2+)-induced lysis of ER and pat-ER are different. PMID- 1747412 TI - [Oxidative iodination of rabbit IgG: localization of markers in an Fc-fragment and effects of modification]. AB - A comparative study of rabbit IgG, both native and modified ones, designed to assess the functional activity of these proteins under oxidative iodination conditions has been carried out. Polyclonal IgG, its antigen-specific fraction and Iodogen as an oxidant were used. Polyclonal antibodies directed against the CH2 domain of IgG, protein A targeted at the CH-2-CH3 domain interface and ferritin testing the conformation of the antigen-binding Fv fragment, were applied as conformational probes for assessing the changes in the IgG conformation. By taking advantage of pepsin proteolysis of [125I]-IgG, from 80% to 92% of the label was found to be localized within the CH3 domain, thus implying the domain-selective nature of iodination, when the degree of modification was below 0.1 atom of iodine per IgG molecule. Yet, when the three above-mentioned conformational probes were used, considerable alterations in the conformation of not only the CH2 domain and CH2-CH3 domain interface, but in the Fv domain being a part of the Fab fragment, were observed. By using competitive enzyme immunoassay for the straightforward comparative evaluation of functional properties of "cold" (native) and 125I-modified IgG, the deleterious effect of the oxidant (Iodogen) rather than iodine atom substitution at the phenolic ring of Tyr residues was shown to be the major determinant of alterations in the IgG molecule. PMID- 1747413 TI - [Membrane reception of thyroid hormones]. AB - Comparative and competitive analyses of thyroxine (T4) and triiodothyronine (T3) binding to highly purified rat liver, brain and lung cell plasma membranes were carried out. The dependence of hormone binding on the time, temperature and concentration was studied. The effects of trypsin and partial delipidation on the binding parameters of thyroid hormones were investigated. Two thyroid hormone binding sites were detected in cell plasma membranes of all tissues under study. The maximal binding of T4 to rat liver membranes and the maximal binding of T3 to rat brain membranes was observed in all experiments, the affinity for T3 being higher than that for T4. An important role of both protein and lipid components of plasma membranes in the membrane reception of thyroid hormones is proposed. PMID- 1747414 TI - [Kinetics of immunoglobulin G transport through the multi-layer epithelial hematic barrier of the respiratory tract]. AB - A new class of drugs is now utilized for in vivo diagnoses and therapy of many widespread diseases. In these pharmacological and diagnostic preparations the active substance is conjugated with a vector which transports the drug to specific biological targets. Monoclonal antibodies are the most commonly used vectors: estimation of their permeability through multilayer and unilayer biomembranes is an important step in the analysis of efficiency of vector drugs. Experiments with Sprague-Dawley rats (mature females weighing 500 to 160 g) have demonstrated the ability of immunoglobulins G to penetrate through the respiratory epithelial-hematic barrier. Using solid phase ELISA, it was found that 5-25% of the total amount of mouse antiinsulin immunoglobulins G1 injected into the trachea under hexenal anesthesia can penetrate into the blood plasma. Accumulation of antibodies in the blood begins 4 hours and ceases 32 hours after the drug application in a dose of 400 micrograms. The kinetics of transmembrane transport is described by an S-like saturation function: C(t) = Cmax/(1+e-(at-b]. Penetration of monoclonal antibodies into the blood is accompanied by their distribution in the organs and tissues as well as by their clearance from the blood plasma. The clearance of monoclonal antibodies is characterized by a 24 hour half-life and is described by an exponential equation: C(t) = C0 x exp-kt. An algorithm for the interaction of these processes which should be taken into account during measurements of the transport of monoclonal antibodies and their complexes through biomembranes is proposed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747415 TI - [Comparison of lipid metabolism in rat liver cells and nuclei during cycloheximide-induced superinduction of nuclear oncogenes]. AB - Using a model of cycloheximide (CHI)-induced expression of nuclear oncogens, a comparative study of metabolism of the major lipid classes in rat liver nuclei and cells was carried out. A short-term activation of sphingomyelinase which preceded on a time scale the maximal accumulation of c-fos and c-myc transcripts was observed both in the cells and in the nuclei. In contrast with the whole cell, the level of phospholipase C activity in the nuclei did not change under conditions of oncogene activation. It was found that the maximal expression of nuclear oncogens coincided in time with cyclic changes in the content of practically all phospholipids and neutral lipids with simultaneous activation of their synthesis both in the cells and in the nuclei. However, in the nuclei the sphingomyelin metabolism activation was predominant. It is concluded that in the nucleus sphingomyelin and its metabolites may influence oncogene expression via nuclear protein kinase C. PMID- 1747416 TI - [Study of sphingomyelinase activity and sphingomyelin and ceramide levels in comparison with other lipid fractions of the cell nucleus in regenerating rat liver]. AB - The changes in the activity of cell nuclear sphingomyelinase at different times of activation of RNA and DNA syntheses in regenerating rat liver were studied. A comparative analysis of the intranuclear content of sphingomyelin and the primary product of the sphingomyelinase reaction, ceramide, as well as of other classes of phospholipids and neutral lipids, was carried out. The changes in the sphingomyelin and ceramide content in the nuclei during the induction of synthetic processes were more conspicuous as compared with other phospholipid classes. Neutral lipids of cell nuclei were also shown to undergo substantial changes. The mechanism of possible involvement of sphingomyelin and other lipids in the regulation of replication and transcription processes is discussed. PMID- 1747417 TI - [The effect of insulin on the catalytic efficacy of rat skeletal muscle hexokinase isoenzyme II]. AB - The effect of insulin on the intracellular localization of rat skeletal muscle hexokinase isozyme II (hexokinase II) was studied in vivo. It was found that after injection of the hormone the glucose concentration in the muscle gradually increases in parallel with the hexokinase II redistribution between the cytosol and the mitochondrial fraction in the direction of the bound form of the enzyme. This effect of insulin is due to glucose, an indispensable participant of the complex formation between the enzyme and the mitochondrial membrane. It was shown that the effect of glucose as a hexokinase II adsorbing reagent is a highly specific one. The hexokinase II binding to mitochondria in the presence of glucose is accompanied by changes in some kinetic properties of the enzyme. A kinetic analysis of catalytic efficiency of the free and bound hexokinase II forms revealed that the catalytic efficiency of hexokinase II within the composition of the enzyme-membrane complex exceeds by two orders of magnitude that of the free enzyme. The data obtained are discussed in the framework of an adsorption mechanism of hexokinase activity regulation in the cell. PMID- 1747418 TI - [Modifying effect of concanavalin A and diamide on erythrocyte sensitivity to cold shock]. AB - The temperature (0 degrees C and 37 degrees C) and the medium tonicity (0.15-1.20 M NaCl) were shown to affect erythrocyte agglutination by concanavalin A. Treatment of cells with lectin caused no significant decrease in the erythrocyte hemolysis upon cooling. Diamide, unlike concanavalin A used at concentrations above 2.0 M decreases the cell sensitivity to the cold shock. The changes in the erythrocyte susceptibility to cooling within the temperature range of 37-0 degrees C correlate with changes in the electrophoretic spectrum of membrane proteins. The progressive decrease in the spectrin bands intensity with a simultaneous formation of high molecular weight protein aggregates not included in the gel composition was observed after diamide treatment. The diamide effect depends on the medium tonicity, at which the treatment was performed, being especially well pronounced in hypertonic media with 0.8-1.2 M NaCl concentrations, the maximal spectrin aggregation being observed under these conditions. It is suggested that the main factor of the mechanism underlying the erythrocyte hypertonic cold shock is the increase in the association of peripheral cytoskeleton proteins with plasma membrane in osmotically dehydrated cells which limits the ability of lipids to adapt during cooling and results in the stabilization of defects in the membrane structure at low temperatures. Diamide eliminates these unfavourable changes eventually resulting in the dissociation of peripheral proteins from the cytoplasmic surface of the membrane on the protein aggregation. PMID- 1747419 TI - [Quaternary structure of uridine phosphorylase from E. coli K-12]. AB - Uridine phosphorylase was isolated from E. coli K-12 cells in a homogeneous state. The molecular mass of the enzyme as determined by gel filtration corresponds, approximately, to a hexamer made up of 27.5 kDa monomers. Evidence for the hexameric structure of uridine phosphorylase was obtained by electron microscopy with numerical treatment of the images. The six monomers within the enzyme molecule are arranged in two layers, three monomers in each, at the apices of a triangular antiprism with a point group symmetry of 32. PMID- 1747420 TI - [Participation of the ATP/ADP antiporter and fatty acids in oxidative phosphorylation uncoupling in squirrel liver mitochondria during winter hibernation and awakening]. AB - The parameters of energy coupling of mitochondria isolated from the livers of hibernating and awakening gophers were studied. The ATP/ADP-antiporter inhibitor carboxyatractylate slowed down the respiration rate, increased delta psi and decreased the ionic conductivity of the inner mitochondrial membrane as measured by the rate of the delta psi decline after addition of cyanide (in the presence of oligomycin and EGTA). A similar effect was produced by BSA, carboxyatractylate being fairly ineffective in the presence of BSA. In hibernating gophers the maximal rate of the uncoupled respiration and the ionic conductivity of the inner mitochondrial membrane were markedly decreased as compared with awakening gophers. The data obtained suggest that in awakening animals fatty acids induce the uncoupling of oxidative phosphorylation by the ATP/ADP-antiporter, this process being simultaneous with the activation of the respiratory chain. PMID- 1747421 TI - [Myosin head structure]. AB - The current data and concepts of the structural organization of the head of myosin, one of the major muscle proteins, are reviewed. The primary structure of the isolated myosin head (myosin subfragment-1) heavy chain and localization in it of sites and groups responsible for the binding and hydrolysis of ATP and myosin interaction with actin, are considered. Evidence is given of reciprocal spatial distribution of these sites and their localization on the myosin head surface. Some present-day concepts on the domain organization of the myosin head and its changes occurring during binding and hydrolysis of ATP, are discussed. A model describing the folding of the heavy and light chains in the myosin head is proposed. PMID- 1747422 TI - [Factors in rat liver cytosol, inhibiting chemiluminescence during nonenzymatic lipid peroxidation]. AB - The effect of normal rat liver cytosol on the level of Fe/ADP-ascorbate-induced lipid peroxidation in the total particulate fraction (mitochondria plus microsomes) has been studied. The intensity of lipid peroxidation was measured using the chemiluminescence technique and by malonic dialdehyde (MDA) production. Dialyzed cytosol significantly decreased the level of chemiluminescence and, to a much lesser extent, the rate of MDA production. Gel filtration on a Sephadex G 200 column led to the appearance of at least three cytosolic fractions which suppressed the low-level chemiluminescence. These fractions differed from one another by their molecular masses, kinetics of chemiluminescence inhibition and effects on the intensity of MDA production. The putative functional role of antioxidative defence factors from rat liver cytosol is discussed. PMID- 1747423 TI - [Activation of (ADP-ribose) polymerase by DNA fragmented by micrococcal nuclease and DNAase I]. AB - Activation of (ADP-ribose) polymerase by DNA fragments obtained by digestion of calf thymus DNA with micrococcal nuclease and DNAase I was studied. It was found that activation of the enzyme is due to its interaction with the terminal parts of double-stranded DNA fragments, the level of activation being independent of the size of DNA fragments. PMID- 1747424 TI - [Age changes in the level of pyridinoline cross-linking and ratio of soluble and insoluble collagen in human rib collagen]. AB - The changes in the content of mature crosslinks with pyridinoline structure and soluble/insoluble collagen ratio in the costal cartilage tissue of human beings aged from 1 month to 57 years were found to be age-dependent. The effect of the pyridinoline crosslink content on the soluble/insoluble collagen ratio in human costal cartilage tissue may constitute no less than 67% of the total influence of the sum of all factors. The pronounced nonlinearity of the studied dependencies points to a possible involvement of a factor(s) other than the pyridinoline crosslink content. PMID- 1747425 TI - [Changes in the lipid and protein components of thymus cell membrane during lipid peroxidation]. AB - Nonenzymatic lipid peroxidation in thymus cell plasma membranes was studied. The composition of lipid and protein components, intensity of fluorescence of the membrane probes (1-anilinonaphthalene-8-sulfonate, 4-dimethylaminochalcon, eosin, pyronin and rhodamine), fluorescence polarization of tryptophan residues of membrane proteins and quenching by acrylamide of intrinsic fluorescence of proteins were determined. Induction of lipid peroxidation by the Fe(2+)-ascorbate system caused changes in the composition and structure of lipids. This was paralleled with changes in the structural-dynamic organization of membrane proteins, transition of some peripheral proteins to the water phase and increased solubilization of integral proteins by Triton X-100. PMID- 1747426 TI - [Immunoenzyme determination of the total level of ceruloplasmin in the serum from patients with hepatocerebral dystrophy]. AB - An immunoenzymatic method for ceruloplasmin analysis (IEA) based on the use of horseradish peroxidase-labelled monospecific antibodies as markers has been developed. IEA can be used for direct measurements of ceruloplasmin in blood serum, as can be evidenced from the coincidence of calibration plots obtained after the use of potassium-phosphate buffer and ceruloplasmin-free sera. The procedure allows the determination of the total content of ceruloplasmin present in the blood sera of patients with hepatocerebral dystrophies both in the active and inactive forms. The minimum ceruloplasmin concentration detectable by this method is 5 x 10(-9) g/ml. The method was used to determine ceruloplasmin levels in the blood of patients with various grades of hepatocerebral dystrophy. Analysis of blood sera from 6 patients revealed that the ceruloplasmin concentrations determined by IEA were very close, whereas the oxidase activities of this protein differed more than 7-fold. The amount of enzymatically active ceruloplasmin as determined from the oxidase activity made up to 10-68% of the total ceruloplasmin content in the sera, depending of the severity of the pathology. PMID- 1747427 TI - [Change in energy metabolism of ascites cancer cells with a decrease in pH]. AB - In Hank's balanced salt solution EL-4 ascites thymoma cells possessed endogenous respiration which was sufficient for the maintenance of their ATP level: pH decrease down to 6.0 had no effect either on endogenous respiration or the ATP level. Glucose had no influence on the respiration of EL-4 cells but inhibited that of Ehrlich ascites carcinoma (EAC) cells by 40% (Crabtree effect); respiration of the both cell lines was strongly (4-fold) inhibited after simultaneous addition of glucose, lactate and pH decrease. EL-4 cells had no endogenous glycolysis; EAC cells showed a low level of glycolysis only after pH decrease. Glucose addition led to activation of glycolysis (both inhibited 2-fold after a decrease of pH down to 6.0. The respiration inhibition at pH 7.3 and 6.0 caused no decrease of ATP depletion when glucose was present in the medium; this result may be due to suppression of ATP consumption. Incubation of EL-4 cells under respiration and glycolysis deficiency conditions resulted in a sharp ATP depletion; pH decrease delayed this depletion. PMID- 1747428 TI - [Kinetics of NADH oxidation of NAD+ reduction by mitochondrial complex I]. AB - The kinetics of the NAD: artificial acceptor-oxidoreductase and delta mu H(+) dependent succinate: NAD(+)-oxidoreductase reactions (reverse electron transfer) reactions catalyzed by the membrane-bound complex I was studied. The values of apparent rate constants of dissociation of complexes of the oxidized and reduced enzyme with NAD+ and NADH were determined. It was shown that the apparent affinity of NADH for the oxidized complex I is by nearly three orders of magnitude as high as that of the reduced one; a reverse correlation is found for NAD+. A kinetic scheme of complex I functioning in the forward and reverse reactions, according to which the free reduced enzyme is not an intermediate of the forward (NADH-oxidase) reaction and the free oxidized enzyme is not an intermediate of the reverse (NAD(+)-reductase) reaction, is proposed. PMID- 1747429 TI - The evolution of a claim in a medical malpractice case. PMID- 1747430 TI - General form for requesting hospital documents. PMID- 1747431 TI - Tax benefits of being self-employed. PMID- 1747432 TI - Liability issues. PMID- 1747433 TI - The seven habits of highly effective people. PMID- 1747434 TI - Unravelling your malpractice insurance policy [continuing education credit]. PMID- 1747435 TI - Biological research in geriatric psychiatry. PMID- 1747436 TI - Positron emission tomography and magnetic resonance imaging: a review and a local circuit neurons hypo(dys)function hypothesis of schizophrenia. AB - A review of brain imaging (PET and MRI) studies on schizophrenia and recent data from neuroanatomy, neurophysiology, neuropathology, neurochemistry, neuropsychology, and cortical organization theory is integrated with the concept of local circuit neurons (LCNs) in a new hypothesis--the local circuit neurons hypo(dys)function hypothesis of schizophrenia--that attempts to explain the pathogenesis and pathophysiology of schizophrenia through a hypofunction (or dysfunction) of the local circuit neurons in prefrontal and limbic-temporal areas. This hypofunction (dysfunction) is then related to the neurocircuitry, neuropsychology, and psychopathology of schizophrenia. PMID- 1747437 TI - Lack of a bimodal distribution of ventricular size in schizophrenia: a Gaussian mixture analysis of 1056 cases and controls. AB - The finding of clinical and laboratory differences between schizophrenic patients with large and small cerebral ventricles has led to the widespread assumption that large ventricles are a marker that characterizes a subgroup of patients with schizophrenia. We reviewed all published English language ventricle-to-brain ratio (VBR) studies in which individual data points were available (schizophrenics: n = 691, medical controls; n = 205, normal volunteers: n = 160). Using a univariate normal mixture model to examine the distribution of ventricular size in each group, we found no evidence of a mixture of Gaussian distributions (i.e., "bimodality") within any of the three groups. The same analysis was then performed on the combined sample of schizophrenic patients and normal and medical controls, respectively. In each case the improvement in fit of a mixture of normal distributions compared to a single component normal distribution was significant. The data do not support the notion that ventricular enlargement is a discontinuous marker of a subtype of schizophrenia. PMID- 1747438 TI - Pretreatment EEG predicts short-term response to haloperidol treatment. AB - This study analyzed the relationship between pretreatment electroencephalogram (EEG) and response to haloperidol medication in a group of acutely exacerbated schizophrenic patients (n = 34). Improvement was assessed after 3 and 6 weeks of treatment; it was measured globally, as decrease in the total score on the Brief Psychiatric Rating Scale (BPRS), as well as multidimensionally through the individual BPRS factors. Relative powers from four clinical EEG frequency bands were employed as predictor variables. Baseline alpha activity was significantly related to clinical response. Higher alpha values were associated with poorer response to treatment. Specifically, improvements on the "thought disturbance" and "hostility-suspiciousness" factors underlied the relationship between the pretreatment EEG and outcome. PMID- 1747439 TI - The effect of tetrahydroaminoacridine (THA) on P300 in Alzheimer's disease. PMID- 1747440 TI - Draft guideline on detection of toxicity to reproduction for medicinal products. PMID- 1747441 TI - Proposal for international guidelines for reproductive and developmental toxicity testing for pharmaceuticals. AB - 1. A Workshop was organized by the Centre for Medicines Research in London, 13th 15th May 1991 to discuss the current situation concerning tests for reproductive and developmental toxicity required for new drug development, and whether a unified series of guidelines could be developed which would satisfy Regulatory Authorities and Scientists worldwide. 2. The international group of experts invited to participate in this meeting reached a consensus regarding the desirability of developing new and flexible guidelines. An approach was proposed based on the state of the art of scientific knowledge in the field of reproductive and developmental toxicology coupled with the minimum use of experimental animals, and taking into consideration the European proposal for a new guideline which has been open for discussion since 1989. 3. Although time did not permit detailed discussion of all study designs, several which are considered to provide acceptable tests for reproductive and developmental toxicity of new therapeutic candidates have been proposed for further discussion. These include the possibility of considerable reduction in duration and size of studies, and numbers of animals used where there is an indication that a low hazard potential exists. 4. Whichever of the combinations are ultimately used in the premarketing assessment, it is most important that the investigators justify in detail the rationale underlying the choice of studies undertaken. This should take into account the specific properties of the drug molecule and its proposed clinical use. 5. This paper reflects the discussions which took place at the Workshop and its publication has been agreed to by the participants. It is intended that it could be used as the basis for discussions of a harmonized approach to reproductive and developmental toxicity testing of pharmaceuticals. As such, it will be made available to regulatory agencies, trade associations and other appropriate groups for their consideration and acceptance, modification or scientific augmentation. PMID- 1747442 TI - Animal toxicology studies on new medicines and their relationship to clinical exposure: a review of international recommendations. AB - Written guidance on the toxicology studies which should be completed to support an application to market a new medicinal product in the EEC, Japan, and the USA is readily available, although the recommendations can vary significantly between the three markets. Less clear are the regulatory authorities' expectations concerning the timing of these studies relative to the clinical development programme. All available guidelines for premarketing toxicology requirements, and the portions thereof needed to support various stages of the clinical trials programme will be reviewed. Significant differences among the three markets and between written guidance and customary practice will be highlighted. The practical implications for the clinical development programme will be identified. PMID- 1747443 TI - The safety of angiotensin-converting enzyme (ACE) inhibitors in moderate hypertension. PMID- 1747444 TI - Androgen in the treatment of refractory anemia. AB - We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups. PMID- 1747445 TI - Enzyme histochemical, immuno histochemical and electron microscopic studies of two cases of leukemic malignant histiocytosis. AB - Two cases of leukemic malignant histiocytosis had similar morphologic and enzyme histochemical findings. Large blasts with low nuclear/cytoplasmic ratios, occasional azurophilic granules, and immature nuclei with nucleoli were seen in peripheral blood and bone marrow smears. Case 1 had occasional erythrophagocytosis, while in Case 2 it was rare. They were peroxidase negative, and very strongly positive by alpha-naphthyl butyrate esterase stain, the latter being inhibited by sodium fluoride. Acid phosphatase stains were also very strongly positive and were inhibited with tartaric acid. They were also stained granularly with PAS. Surface marker analysis revealed myeloid surface antigens, CD11+, CD13+ and HLA-DR+ in Case 1, and CD11+, CD13+, CD33+ and HLA-DR+ in Case 2. Immunoperoxidase stains of bone marrow biopsies revealed that lysozyme was positive in both cases. S-100 protein was strongly positive in Case 1, but weakly so in the skin tumor and negative in the bone marrow of Case 2. Electron microscopy showed both cases to be myeloperoxidase negative and rich in cytoplasmic organelles, such as lysosomes, mitochondria, and endoplasmic reticuli. Nuclei were irregularly shaped and nucleoli were present in virtually all the cells. These findings suggest that the malignant histiocytes in these two cases derive from bone marrow macrophages, and S-100 protein can also be detected in monocyte-macrophage derived histiocytes. PMID- 1747446 TI - Gene amplification of Japanese non-Hodgkin lymphoma with involvement of the BCL2 gene. AB - Twenty cases of Japanese non-Hodgkin's lymphoma with B cell markers were studied with respect to their immunoglobulin heavy (IgH) chain gene loci on chromosome 14 and BCL2 loci on chromosome 18. All of the 20 cases showed IgH gene rearrangement on at least one of the alleles. Molecular analysis using two chromosome 18 specific DNA probes (pFL1 and pFL2) showed rearrangement of the BCL2 region in three of 20 cases. As these three samples showed the rearranged allele of the IgH gene comigrating with that of the BCL2 gene, polymerase chain reaction (PCR) was carried out to amplify the juncture between IgJH on chromosome 14 and BCL2 on chromosome 18. In all of these three cases, gene amplification between the two loci was found to occur, indicating that molecular mechanisms involved in this type of chromosomal translocation in Japan might be similar to cases in the United States (U.S.) in a limited number of cases. Furthermore, this amplification technique revealed minimal tumor cells circulating in peripheral blood, even though lymphoma cells could not be identified morphologically. Thus, the PCR technique is useful for both the detection of minimal tumor cells as well as for the determination of the molecular nature of chromosomal translocation in some of Japanese cases. PMID- 1747447 TI - Establishment and characterization of a new human Bence Jones-type myeloma cell line, NOP-2. AB - A new human myeloma cell line NOP-2, producing immunoglobulin (Ig)-lambda-light chain was established from a patient with Bence Jones-type multiple myeloma. Morphologically, the cell line had plasmacytoid characteristics by light- and electron-microscopic examination. Phenotypic studies of NOP-2 cells revealed no surface Ig, but they were positive for cytoplasmic Ig-lambda, OKT10 (CD 38), and PCA-1. Epstein-Barr nuclear antigen was not detected. Chromosomal abnormalities of t(11;14) and t(8;22) were found in both NOP-2 cells and the original myeloma cells obtained from the patient. NOP-2 cells produced and secreted Ig-lambda light chain, but lacked immunoglobulins of any heavy chains. Rearrangements of both immunoglobulin heavy- and light-chain genes were observed in NOP-2 cells, though the cells expressed detectable mRNA only for Ig-lambda light chain. This cell line may serve as a useful model for understanding the hierarchy of human immunoglobulins and the pathophysiology of Bence Jones-type multiple myeloma. PMID- 1747448 TI - Expression of H-related antigen on human megakaryocytes and megakaryocytic leukemia cells. AB - A mouse monoclonal antibody (MoAb), MG-2, was produced by immunizing a characterized human megakaryoblastic cell line, MEG-01. Since MG-2 reacted with erythrocytes of all ABH blood groups except Oh (O Bombay), and since anti-H MoAb inhibited MG-2 binding to MEG-01 cells, MG-2 is considered to recognize a molecule closely related to blood group antigen H. MG-2 reacted more strongly with normal smaller sized megakaryocytes than with larger sized ones, and not with platelets. The expression of the intrinsic H-related antigen on MEG-01 cells decreased concomitant to megakaryocytic differentiation induced by phorbol esters. This H-related antigen was expressed on leukemia cells with the megakaryocytic features from blast crisis of chronic myelogenous leukemia and acute megakaryoblastic leukemia. PMID- 1747449 TI - Thrombopoietic factor enhances murine megakaryopoiesis induced by recombinant erythropoietin. AB - Partially purified thrombopoietic factor (TPF) potentiated in vitro murine megakaryopoiesis induced by recombinant human erythropoietin (rh-Epo). High doses (2.5-10 units) of rh-Epo generated a considerable number of megakaryocytes in a dose-dependent manner in a serum-free liquid culture, whereas low doses of rh-Epo (0.5-1 units) failed to generate megakaryocytes. The addition of high doses of rh Epo and TPF caused a significant increase of megakaryocytes in comparison with high doses of rh-Epo alone. Furthermore, low doses of rh-Epo with TPF caused generation of a small number of megakaryocytes, although TPF alone did not generate megakaryocytes. In addition, TPF enhanced the acetylcholinesterase (Ach E) activity of megakaryocytes induced by rh-Epo. The potentiating effects of both factors, rh-Epo and thrombopoietic factor, may play an important role in thrombocytopenic states in vivo as well as in in vitro megakaryopoiesis. PMID- 1747450 TI - Long-term cultivation of an interleukin-3-producing cell line in a chemically defined protein-free medium. PMID- 1747451 TI - Transport of ferritin from Kupffer cells to liver parenchymal cells. Morphological and immunocytochemical observations. AB - In attempting to determine the pathway of ferritin from Kupffer cells to liver parenchymal cells, anionic iron colloid particles of a ferric hydroxide-potassium polyvinyl sulfate complex (Fe-PVS) were injected intravenously into blood depleted anemic rats. After iron loading, the process of ferritin formation and the daily change in the latter's distribution in the liver were studied by ultrastructural-immunocytochemical techniques. Three days after Fe-PVS injection, a mass of reaction products of ferritin was found in Kupffer cells, though not in the sinusoidal endothelial or parenchymal cells. Four days post-Fe-PVS injection, however, reaction products in Kupffer cells disappeared, while appearing in parenchymal cells. Observations at 3.5 days after the injection revealed heavy deposition of reaction products in the sinusoid and Disse's spaces as well. Electron microscopic observation of tissue sections treated with bismuth subnitrate taken at this stage revealed diffuse dispersion of ferritin particles in the cytoplasmic matrix of parenchymal cells as well as in the sinusoid and Disse's spaces. Ferritin particles were not found in the coated pits and vesicles of the Kupffer cells and parenchymal cells. Four days after injection, ferritin particles were found in clusters in the cytoplasm of the parenchymal cells and also in their lysosomal bodies. The results indicate that ferritin synthesized in Kupffer cells is released into sinusoidal and Disse's spaces and then accumulated in parenchymal cells. PMID- 1747452 TI - Effects of iron on lipid peroxidation. AB - To elucidate the effects of iron on lipid peroxidation, three kinds of assays were done. (i) The effects of intravenous injection of single doses of iron dextran (100 mg iron) on lipid peroxidation in various tissues and the blood plasma of rats were examined by the thiobarbituric acid reaction. Malondialdehyde concentrations were significantly elevated in the spleen, heart, and plasma 3 h after injection, whereas significant increases were observed in the liver and adipose tissue at 24 and 48 h, respectively. In the liver and spleen, the elevated malondialdehyde concentrations persisted until Day 28. In contrast, levels were reduced in the heart and adipose tissue within 4 weeks after iron injection. Plasma malondialdehyde concentrations were 70-times that of controls at 24 h after iron injection. The level subsequently decreased sharply by Day 6. In red blood cells, lipid peroxidation was not affected by iron. Malondialdehyde levels were correlated with the iron contents of the liver, spleen, heart, adipose tissue, and plasma (r value range 0.39-0.88, p less than 0.05). Furthermore, there was a strong correlation in the liver and spleen at iron levels below 2,000 micrograms/g (r = 0.94, p less than 0.0001; r = 0.94, p less than 0.0001, respectively). (ii) In vitro experiments demonstrated that the addition of iron as ferric chloride, iron dextran, ferritin, and hemosiderin to normal liver homogenate accelerated malondialdehyde production. However, such increases were less than 10% of those caused by equivalent iron in the liver homogenate of iron treated rats. (iii) Compared to controls, spleens from eight thalassemia patients showed a high level of malondialdehyde and iron. PMID- 1747453 TI - Successful 0 degree C liquid preservation of red blood cells. AB - In an effort to determine the lowest acceptable temperature for liquid preservation of red blood cells, the latter were stored at 5, 0, -2 and -5 degrees C. When polyvinylchloride (PVC) bags plasticized with di(2 ethylhexyl)phthalate (DEHP) were used as containers, hemolysis of red cells stored for 42 days at 0 degree C was lower than at the other three temperatures. Adenosine triphosphate (ATP) levels, morphology scores, and deformability indices were also best maintained at 0 degree C, and erythrocyte osmotic fragility did not increase at that temperature. On the other hand, when blood was stored in glass bottles at 0 degree C, hemolysis and erythrocyte osmotic fragility increased. The addition of DEHP to red cells stored in glass bottles at 0 degree C decreased hemolysis and erythrocyte osmotic fragility to levels equal to those in PVC bags. Thus, storage of red cells can be done at temperatures as low as 0 degree C, if PVC bags are used as the container. Previous negative assessments of storage temperatures below 4 degrees C, may be due to the use of glass bottles as containers for blood preservation. PMID- 1747454 TI - Iron balance following recombinant human erythropoietin therapy for anemia associated with chronic renal failure. AB - Erythrokinetic changes before and after rHuEPO therapy in 15 anemic patients with chronic renal failure undergoing maintenance hemodialysis were analyzed by means of ferrokinetics and measurement of red cell mass and survival. To estimate the change in iron status no exogenous iron was administered during the observation period unless a lack of response due to iron deficiency was confirmed. During 13 29 weeks of therapy there was an increase in red cell mass from 12.5 +/- 1.7 mg/kg to 20.1 +/- 3.6 ml/kg, compatible with the increase in hematocrit from 21.5% to 31.8%. In ferrokinetics the plasma iron disappearance time (t1/2) shortened from 163 +/- 44 min to 92 +/- 24 min. The plasma iron turnover rate rose from 0.39 +/- 0.10 mg/dl per day to 0.56 +/- 0.11 mg/dl per day. Serum ferritin levels were decreased from 160 +/- 115 ng/ml to 26 +/- 22 ng/ml, although there was only one patient showing poor response to rHuEPO because of iron deficiency. The increase in red cell volume correlated with the decrease in serum ferritin levels (p less than 0.02). There was no significant difference in these ferrokinetic parameters between transfused and non-transfused patients not only before, but also after, rHuEPO therapy. It is suggested that an elevation of about 8 ml/kg of red cell mass (approx. 10% as hematocrit) exhausts iron stores in the majority of patients. PMID- 1747455 TI - The role of diferric transferrin in iron absorption and transferrin concentration in rat pancreatic juice and milk. AB - Transferrin (Tf) was found immunologically in pancreatic juice of normal rats at a concentration of 0.28 +/- 0.10 mg/ml but was found to be approximately 4-times higher in iron-deficient rats. Iron saturation of pancreatic Tf of normal rats was 40% and similar to that of serum Tf. Approximately 27% of a dose of iron from 59Fe-diferric Tf was absorbed through the ligated segments of proximal intestine in normal rats. The iron absorption ratio of 59Fe-diferric Tf was higher from the duodenal and jejunal segments than the ileum and significantly inhibited by monodansylcadaverine (MDC) or 20-times excess of unlabeled diferric Tf. The presence of Tf receptors was demonstrated by specific binding of 125I-diferric Tf to the brush border membrane vesicles of the small intestine in normal rats. The binding was not inhibited by the presence of albumin or IgG. The association constant (Ka) was 1.03 +/- 0.50 x 10(8) M-1 and number of binding sites was 5.10 +/- 0.96 x 10(12) sites/mg protein in the proximal intestine. The number of binding sites for Tf was higher in the proximal intestine than in the distal one. These results suggested that some iron was absorbed as diferric Tf into enterocytes through receptor-mediated endocytosis. PMID- 1747456 TI - Spontaneous remission in pure red cell aplasia associated with thymoma. AB - A 57-year-old woman with thymoma-associated pure red cell aplasia (PRCA) manifested spontaneous recovery of erythropoiesis. Anemia recurred before the surgical removal of her thymoma, however, and the second anemic remission following surgery did not occur promptly. In this report, we describe a rare occurrence of spontaneous remission in PRCA. PMID- 1747457 TI - In vitro chemosensitivity of lymphoblasts at relapse in childhood leukemia using the MTT assay. AB - Lymphoblasts from 21 previously untreated patients with acute lymphoblastic leukemia (ALL) and 31 patients in relapse were tested for chemosensitivity. Blast cells were cultured with 22 anticancer drugs for 4 days and assayed by MTT dye using a scanning microplate photometer. The percent cytotoxicity index (%CI) and LD50 (micrograms/ml) were calculated for each drug. The mean absorbances (+/- S.D.) of 1 x 10(5) cells in the untreated group and relapsed groups in control wells were 0.219 (+/- 0.126) and 0.385 (+/- 0.147), respectively (p less than 0.01). Cells in the untreated group were more sensitive in vitro to vincristine, prednisolone, L-asparaginase (L-ASP), vinblastine, 5-fluorouracil, epirubicin, bleomycin (BLM), and etoposide (VP16) with respect to the %CI value and to L-ASP, VP16, BLM, and mitoxantrone with respect to the LD50 value than those in the relapsed groups. In contrast, no significant differences were observed for the other 13 drugs. There was also a significant difference in sensitivity within the relapsed group--13 having good clinical response and 15 showing no response to chemotherapy--with regard to four drugs, mitomycin C, neocarzinostatin, L-ASP, and teniposide. Cells in the relapsed group had more heterogeneous chemosensitivity than those in the untreated group, and divided into sensitive and resistant types, but large interindividual differences existed. The MTT assay and LD50-drug resistance percentile curves are useful for the selection of effective drugs in both untreated and relapsed patients with acute leukemia. PMID- 1747458 TI - Hypereosinophilic syndrome evolving to acute lymphoblastic leukemia. AB - We report a case of hypereosinophilic syndrome (HES) which later evolved into acute lymphoblastic leukemia (ALL). A 37-year-old man showed typical clinical manifestations of HES: pulmonary infiltrates, erythematous skin rash, deep vein thrombosis, endomyocardial fibrosis, and diffuse central nervous system dysfunctions. Although he was treated with prednisolone and hydroxyurea, marked eosinophilia persisted and lymphoblasts gradually increased in the bone marrow. He died of severe disseminated fungal infection after anti-leukemic therapy. Autopsy revealed marked fibrous thickening of the endocardium, bilateral common iliac vein thrombosis, and chronic hepatitis with fibrosis. Neither eosinophilic nor leukemic cell infiltration was seen in any tissue at autopsy. Including this case, 24 patients with ALL and hypereosinophilia have been reported in English language literature. We discuss the relationship between eosinophilia and ALL, and the mechanisms, particularly the role of eosinophil cationic protein (ECP), in causing various organ system dysfunctions in HES. PMID- 1747459 TI - Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study. AB - A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma. PMID- 1747460 TI - Ph1-positive acute lymphoblastic leukemia associated with an isochromosome 17q. AB - We report a patient with Ph1-positive acute lymphoblastic leukemia (ALL) having i(17q) in whom bony lesions were the initial clinical manifestation. The patient was a 53-year-old male who began to have pains in his left hip early in March 1985. Relevant findings on admission included: WBC 21,300/microliters; blast cells 73.5%; peripheral blood blast cells, peroxidase (-), PAS (-) and esterase ( ); cytoimmunologic markers, Ia(+) cells 49.1%, CD10(+) cells 67.1%, CD20(+) cells 75.1%; positivity for TdT, and Ph1(+); and i(17q) upon chromosomal analysis. These findings led to a diagnosis of ALL with Ph1(+),i(17q). This case seems to represent an exceedingly rare instance of Ph1(+),i(17q) ALL in which the differential diagnosis between blast transformation of CML and Ph1(+) ALL was initially difficult to make. PMID- 1747461 TI - Aplastic anemia in a patient receiving tamoxifen. PMID- 1747462 TI - [Microvesicles in the developing synapses]. AB - The sensomotor cortex and nucleus caudatus of the embryonal (14-22 days) and newborn rats have been investigated by electron microscopic method. There were described two groups of microvesicles (10-20 nm in diameter) with smooth and rough external surface. They differ from other vesicular components of the developing synapses (such as synaptic vesicles, vesicles of growing conus and other) by the minimal size, structure and localization. Microvesicles with the rough external surface are found only at that moment when the membranous specialization of the further synapse from desmosomes begins to form. They are found along the membranes of active contact zone and are correlated with the degree of differentiation of these membranes. Microvesicles with the smooth external surface are found during the all period of synaptogenesis. They are found either in presynaptic terminal freely or they are attached to presynaptic membrane where they form cluster of microvesicles and they can be found on the surface of synaptical vesicles too. In this article the functional role and genesis of microvesicles are discussed. PMID- 1747463 TI - [Adrenergic nature of vagal acceleration of heart beat in frogs]. AB - Acceleration of heartbeats occurring during the irritation of vagal nerve was discovered as early as in 1846. Many hypotheses about mechanisms of its appearance proved to be not confirmed. Some authors (researchers) considered that the accelerated effect resulted from secreting a small amount of acetylcholine by vagal nerve. We discovered the cause of this groundless opinion and determined that vagal acceleration of heartbeats in frogs was accomplished, partially, by sympathetic fibres of vagal nerve, partially, by catecholamines secreted, probably, from chromaffin cells. PMID- 1747464 TI - [Effects of endogenous opioids on the development of reproductive function in rats]. AB - The influence of opioid peptide on the process of formation of reproductive function in rats was studied. Administration of beta-endorphin to neonatal female rats did not affect the concentrations of oestrogen and androgen receptors in the hypothalamus and pituitary, whereas the content of testosterone receptors was significantly higher in both hypothalamus and pituitary. Chronic administration of beta-endorphin to both female and male rats does not affect the concentration of sex hormones. The results obtained indicate that chronic administration of beta-endorphin to neonatal female rats lead to formation of instable contacts in the mechanism of regulation of hypophysis gonadotropic function. PMID- 1747465 TI - [Characteristics of formation of the generator of pathologically increased excitation (epileptic focus) in the sensorimotor cortex of the brain in rats during its rhythmic electric stimulation]. PMID- 1747466 TI - [Lipid peroxidation in the kidneys of rats with nephritis induced by nephrotoxic serum and proteinuria induced by albumin overload]. AB - Lipid peroxidation (LPO) stimulated by ascorbate was studied in renal cortex of 20 rats with nephrotoxic nephritis (NTN) and of 9 rats with proteinuria induced by a 3-day course of i. p. injections of the human serum albumin. At the early stages of NTN (0.5 h. and 3 h.) LPO activities were of the same values as in control rats. A small decrease in renal cortex LPO was found on the 4-th day of NTN when nephrotic syndrome has been developed. A significant reduction in LPO activity was observed on the 16-th day of NTN characterized by a more pronounced nephrotic syndrome. LPO activity in renal cortex of the rats with albumin overload proteinuria was also reduced. An inhibitory effect of proteinuria on LPO activity in kidney is discussed. PMID- 1747467 TI - [Corazol kindling in rats with different tolerance to hypoxia]. AB - Research was conducted studying the peculiarities of development of pharmacological kindling in rats with different tolerance to hypoxia. Kindling was evoked by injecting subconvulsive doses of corazol (25 mg per kg) every day. Intensity of convulsions was expressed in points. Reliable distinction in intensity of convulsion between low-tolerant rats and high-tolerant rats to hypoxia was found on the 17th day of stimulation; amongst the group of low tolerant rats the intensity of convulsions was found to be 2.46 + 0.30 points, and amongst the group of high-tolerant rats--1.20 + 0.22 points (p 0.05). On the 23rd day of injection the preparation convulsions in the group of low-tolerant rats reached up to 4.00 + 0.20 points and in the group of high-tolerant rats 2.28 + 0.45 points (p 0.01). The changes of violation of behavior were found to be different. Thus, the higher the individual resistance to hypoxia, the more is the resistance of the animal to the effect of epileptogens. PMID- 1747468 TI - [Possibilities of using peripheral blood erythrocytes of rats and man in the detection of long-term action mutagens]. PMID- 1747469 TI - [Combined effects of desialylated and glycosylated low density lipoproteins on lipid content of human aortic intima cells in vitro]. AB - We have studied a combined effect of glycosylated low density lipoproteins (LDL) on the cholesterol content of cells cultured from unaffected human aortic intima. Native LDL did not alter the intracellular cholesterol level while glycosylated LDL taken in the concentration of 50 and 100 mg/ml increased the cell cholesterol content by 30 and 70 percent, respectively. The effect of the same concentrations of glycosylated LDL treated with neuraminidase (desialylated-glycosylated LDL) was twice as powerful. Desialylated LDL in the concentration of 50 and 100 mg/ml raised the cholesterol level by 1.4- and 2.1-fold, respectively. Simultaneous incubation of cells with glycosylated (50 mg/ml) and desialylated (50 mg/ml) LDL brought about a 3.4-fold increase in intracellular cholesterol. The obtained data suggest that intensive development of atherosclerosis in diabetes mellitus may be partially explained by synergic effects of desialylated and glycosylated lipoproteins as well as LDL with both types of modification. PMID- 1747470 TI - [Calcium-binding properties of tissue proteins after kidney allotransplantation]. AB - The kinetics of calcium binding to tissue substrates in hypercalcaemia, induced by intravenous constant rate infusion of calcium gluconate were studied in 19 patients after renal transplantation and in 14 healthy volunteers. Langmuir, Scatchard and Hill analysis revealed the positive cooperative mechanism of calcium binding to tissue in all patients and in healthy volunteers. These results provide indirect evidence of binding of calcium to tissue proteins. The significant decrease of the values of specific buffer capacity of tissue proteins, pool of exchangeable calcium and also the effective Ka were observed in 37% of patients. These changes are proposed to play a role in the pathological calcification of vessels and soft tissues in patients after renal transplantation. PMID- 1747471 TI - [Respiration of rat brain mitochondria in hyperoxia and normoxia]. PMID- 1747472 TI - [Antiepileptic effects of nifedipine]. AB - In experiments on freely moving male Wistar rats it was shown that nifedipine in a dose 10 mg/kg (i.p.) suppressed the penicillin-induced focal epileptic activity in cerebral cortex. A similar suppressing effect of nifedipine was shown on acute generalized tonic-clonic pentylenetetrazol (PTZ) seizures (75 mg/kg, i.p.). Nifedipine in the same dose was not effective on chronic PTZ administration (PTZ kindling, 30 mg/kg i.p. during 28 days): when injected 30 min before each PTZ administration it didn't delay the development of kindling induced seizure susceptibility and had no effect on the severity of seizures. The administration of nifedipine in a dose of 10 or 30 mg/kg to control kindled animals which had not been treated with nifedipine had no influence on the severity of seizures provoked by a testing dose of PTZ (30 mg/kg i.p.): its intensity was similar to that of caused by PTZ injection along. PMID- 1747473 TI - [Interactions of neurotropic drugs with phosphatidylcholine bilayer. Effects on sorption of polyvalent cations]. AB - It is found that neurotropic drugs, whose molecules have positively-charged amino groups and a considerable hydrophobic region (in size), can be incorporated into the phospholipid bilayers. This results in a decrease of the lifetime of Pr3+ cations in the membrane-associated state. No correlation was found to exist between local anaesthesia activity of the study drugs and its capability of displacement polyvalent cations from the membrane surface. PMID- 1747474 TI - [Interrelations of cellular and humoral immune response and different doses of sheep erythrocytes in mice]. AB - In experiments on CBA and C57BL/6 mice the generation of antibody-forming cells respectively either in the popliteal lymph nodes or spleen as well as a rate of delayed type hypersensitivity response (DTHR) on the background of subcutaneous (into foot) or intraperitoneal injection of different doses of sheep erythrocytes (from 10(4) to 10(8)) have been studied. In so doing two types of immune response can be isolated on the dependence upon the sensitivity threshold to antigen of DTHR and humoral immunity. Thus in C57BL/6 mice the antigen threshold for DTHR is of one time (in intraperitoneal immunization) or of a two times (in subcutaneous) lower order than for antibody response. In CBA line mice under subcutaneous immunization there can be seen quite an opposite picture while intraperitoneal immunization causes exact correlation of antigen threshold for cellular and humoral immune response. PMID- 1747475 TI - [Functional activity of natural killers and T-killers in transplantation of the ovary in mice]. AB - The activities of natural killer (NK) cells and T-killers of mice after transplantation of allogeneic ovaries were studied. It was shown that during first month after transplantation cytotoxic and membrano-toxic activities of these effector cells were increased. Activation of NK and T-killers depends on tension of transplantation immunity and may serve as prognostic criteria of rejection. PMID- 1747476 TI - [Immunomorphological changes in the mouse brain after intracerebral administration of a neurotropic strain of influenza virus]. AB - The work dealt with intracerebral inoculation of 150 mice with neurotropic strain of influenza virus A/WSN/33. Virological and immunohistochemical study of virus localization in the mice brain was carried out. It was shown that virus reproduction in ependymal lining cells and plexus choroideus epithelium is followed by destruction of cells and uptake of disintegration products by macrophages. Since the influenza infection is followed by a large number of macrophages involved in gene expression of the main histocompatibility complex, the development of autoimmune reaction with the formation of autoantibodies to brain specific antigens can't be ruled out. PMID- 1747477 TI - [Immunocytochemical analysis of interleukin-1 beta production by human monocytes]. AB - IL-1 was localized within the cytoplasm of human blood monocytes by indirect immunofluorescence using polyclonal rabbit antibodies. After LPS stimulation first IL-1-positive cells appeared at 2 hours and maximal intracellular IL-1 concentration was observed at 10-24 hours when nearly 90% monocytes were labeled with subsequent decline at 48 hours. The highest intracellular IL-1 content preceded its maximal level in cell supernatants. PMID- 1747478 TI - [Activation of phospholipase hydrolysis in the process of oxidative cell damage]. AB - Effect of tert-butyl hydroperoxide toxic action on phospholipase A2 activity and the changes in phospholipid composition from mastocytoma P815 cells were investigated. Oxidative damage of tumor cell membranes was accompanied by the release of arachidonic acid from membrane phospholipids and the accumulation of lysophosphatidylcholine, the product of phospholipase A2 reaction and a potent detergent. Tert-butyl hydroperoxide also increased relative contents of sphingomyelin, phosphatidylserine and phosphatidic acid in tumor cell membranes. It is possible that phospholipase A2 activation and the changes of phospholipid molecular species contents may cause the damage of cell membrane stability. PMID- 1747479 TI - [Synthesis of tumor necrosis factor-alpha (TNF-alpha) by human monocytes in vitro]. AB - The presence of TNF-alpha mRNA and protein in circulating human blood monocytes isolated by continuous Percoll gradient fractionation was studied. The technique of RNA isolation from the blood samples was used to study TNF-alpha mRNA expression. It was shown that human blood monocytes of healthy donors contained no presynthesized pool of TNF-alpha mRNA as well as no TNF-alpha protein. PMID- 1747480 TI - [Use of liposomes for the association of foreign genetic material to spermatozoa]. AB - The binding of liposomes of different composition with sperm cells and their effect on cell behaviour were studied. Experiments have demonstrated, that liposomes, containing positively charged phospholipids, had maximal degree of association with sperm cells. Besides, liposomes seem to be nontoxic for sperms and do not change the functional activity of the latter. Theoretically, sperm cells may serve as a natural vector for transfer of liposome-encapsulated DNA into the ovary cells of animals for obtaining transgenic animals. PMID- 1747481 TI - [Formation of cointegrates between F-like conjugate plasmids]. PMID- 1747482 TI - [Prevention and correction with nonopiate analog of leu-enkephalin of disorders induced in the liver of newborn white rats by prenatal hypoxia]. AB - The newborn rats after 48 hours after the birth were used in the study. The prenatal hypoxia caused the development of hypotrophy. Index of labeled 3H thymidine nuclei decreased 1.5 fold, mitotic index decreased 1.4 fold. The content of aberrant figures of mitosis increased 2.6 times. Hexapeptide injection before hypoxia reduced the alterations caused by hypoxia, the data of body and liver weight did not differ from the control level. PMID- 1747483 TI - [Hepatocytes from the liver of mice with experimental post-toxic cirrhosis stimulate in heterokaryons DNA synthesis in the nuclei of resting fibroblasts of the NIH 373 line]. AB - Hepatocytes from mouse liver with experimental post-toxic cirrhosis (received by means of 10-12 inhalations with CCl4) were fused with serum-deprived (0.2%) resting NIH 3T3 mouse fibroblasts to elucidate mechanisms of liver stroma cells proliferation at cirrhosis. After fusion, nuclei of fibroblasts in such heterokaryons were found to enter into S-period without any exogenous stimulation of cell proliferation (in the medium with low content of serum). The obtained data allow us to suggest that hepatocytes from mouse liver with experimental post toxic cirrhosis can produce and secrete into the medium (blood) factor (s) capable of stimulating the mesenchymal origin cell proliferation. PMID- 1747484 TI - [Thermal effect existing in the action of carbon dioxide laser on the bone tissue]. AB - In the experiments in vitro we have studied the influence of carbon dioxide laser radiation on bone tissues of man. We have found out the range and thermal effect dependence on the density of laser energy, the character and thickness of radiated tissues. We have determined the dynamics of temperatures at any time. The received results give us the possibility to differentiate the optimum regimen of radiation. PMID- 1747485 TI - [Role of mast cells in reactions of the blood system in inflammation]. AB - On the model of the acute infectious peritonitis in mice it is shown that the previously osmotic disruption of the peritoneal mast cell population remarkably affects the inflammatory focus, blood and bone-marrow leukocytic reactions. The initial neutrophil accumulation increase and the earlier and more intensive leukocytosis and activation of granulo-monocytopoiesis are established. At the same time the kinetics of monocytes in inflammatory focus is expressed weaker and testifies to the prolongation of the inflammatory response. Thus, in the natural inflammatory conditions mast cells of the inflammatory focus directly or indirectly modulate leukocytes and hematopoiesis. PMID- 1747486 TI - [Participation of peptide hydra morphogen in the regulation of proliferation processes in different tissues of white rats]. AB - The PMH influence on proliferation processes in some tissues of white rats was studied. PMH injections in doses 10.0 mkg/kg and 100.0 mkg/kg stimulated the processes of DNA--synthesis after 24 hours in corneal and tongue epithelium. The direct dose-dependent effect was revealed. PMH in dose 10.0 mkg/kg activated the proliferative processes in the stomach epithelium and thymus cortex. after 24 hours too. The given dose of PMH caused trustworthy decreasing of proliferative activity in thymus after 4 hours. The stimulation of DNA-synthesis and acceleration of mitosis were found after 5-times application on white rat's corneal with 100 nM PMH solution. PMID- 1747487 TI - [Reaction of cell population of the rat nucleus tractus solitarius to disorders of carbohydrate metabolism]. AB - Cell responses in disparate subnuclei of the nucleus tractus solitarius (NTS) to experimental alloxan diabetes were studied using light microscopic morphometric methods. Histophysiological features in seven of fourteen cell divisions distinguished in the rat NTS, demonstrated their dependence on impaired carbohydrate metabolism. The data obtained are consistent with the hypothesis of the NTS involvement in the control of carbohydrate homeostasis. PMID- 1747488 TI - [A morphofunctional study of an experimental staphylococcal and Pseudomonas aeruginosa infection in rats with the background of administration of a synthetic analog of endogenous opioids--dalargin]. PMID- 1747489 TI - [Autoradiography of protein synthesis as a method of assessment of morphofunctional changes in brain structures]. AB - A combination of two groups of autoradiography technique (for a hole brain and individual cells) was applied with using 3H-leucine to evaluate the changes of brain functional activity on the level as anatomical structures and as different type neurons. It was found that Wistar rats with lowered motor activity induced by 3-4 weeks treatment with L-DOPA 100 mg/kg displayed the motor nuclei of the brain stem the cerebellum as highly labelled structures and the motor cortex and n. caudatus as feebly ones in comparison with control. However, a quantitative assessment of silver grains over the neurons of layers III and V of motor cortex and n. caudatus showed not only a significant increase of labelling, especially in neurons of layer V on 174%, in comparison with control but revealed unequal labelling of different type neurons. It was concluded that the applied two groups of autoradiography technique can be a useful approach to assess the brain functional activity. PMID- 1747490 TI - [Use of the procedure of photo-oxidation of fluorescent preparations of autopsy material of the human brain for light and electron microscopy]. AB - Neurons and fibers from human autopsy material were labeled by application of Lucifer Yellow or diI. Dye-filled neurons and fibers were immersed in a diaminobenzidine and potassium cyanide solutions and irradiated with epifluorescent illumination until all visible fluorescence had faded. This simple photo-oxidation procedure resulted in the autopsy human tissue of a stable, nonfading, brown reaction product, visible with the light microscope providing a Golgi-like image, and EM level. This methodological procedure was successfully used for revealing detailed morphology of neurons with dendritic spines, axons with collaterals and varicosities in the human cortical areas and hippocampus. PMID- 1747491 TI - [Ultrastructure of liver cells of shrews]. AB - It was established that the hepatocytes of least shrew (Sorex minutissimus) contained 1-2 nucleus with wide nuclear pores and big nucleolus. There are abundant mitochondria with numerous crists in their matrix (many organelles were divided along the crists). Each mitochondrion was surrounded by the cistern of granular endoplasmic reticulum. The ultrastructure of Golgi complex (1-2 flat cisterns, small vesicles] indicated that the bile was secreted often, by small portions, that was the adaptation to repeated fractional feeding. There were many peroxisomes in the cytoplasm of hepatocytes. Lipid droplets were absent, glycogen granules were not at all hepatocytes. Sinusoidal cells had the usual structure. All sinusoids were open and consisted of the erythrocytes, fragments of hepatocyte cytoplasm and myelin figures in its lumen. PMID- 1747492 TI - [Suppression of epithelial cell proliferation in mice by splenocytes from unilaterally sialoadenectomized syngeneic donors]. AB - Partially hepatectomized CBA mice immediately after the operation were intra orbitally injected with splenocytes of intact (I), Sham-operated (SH-0) or unilaterally sialadenectomized (USAE) syngenic donors. It was shown that splenocytes from USAE donors in contrast to their types of splenocytes acutely suppress the mitotic activity of hepatocytes in the regenerating liver 48 and 72 h after their transfer. Splenocytes isolated 17, 144 and 168 h after removal of submandibular (together with sublingual) gland had the biggest inhibiting ability. Similar effect was obtained in respect of corneal epithelium due to administration of USAE mice splenocytes 17, 48 and 72 h after surgery. Operated recipients are more susceptible to the action of splenocytes from USAE donors, than the non-operated ones. PMID- 1747493 TI - Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study. AB - The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects. PMID- 1747494 TI - Combined therapy with 5-aminosalicylic tablets and enemas for maintaining remission in ulcerative colitis. AB - A combined therapy with 5-aminosalicylic (5-ASA) tablets (1.6gr/day) and 5-ASA enemas (4gr/twice weekly) was evaluated for maintaining remission of ulcerative colitis in 40 patients. All patients were in complete remission which had been maintained for at least 1 month. The remission was assessed by clinical, endoscopic and histological criteria. Clinical and endoscopical evaluations were performed at intervals of 2 and 6 months, respectively. The relapse-rate associated with this combined therapy was 7.5% at 6 months and 16% at 12 months. In comparison with previous investigations using continuous sulphasalazine, our study showed that the combination of 5-aminosalicylic tablets and enemas provided low relapse rates both at 6 and 12 months, suggesting a potential effectiveness in this form of treatment. Further studies are needed to confirm this result with controlled clinical trials. PMID- 1747495 TI - Hepatic damage after danazol treatment. AB - A case of liver damage following treatment with Danazol for fibrocystic breast disease is reported. The findings are based on liver histology and the exclusion of other causes of liver damage. PMID- 1747496 TI - Bacterial N-nitrosation and gastric carcinogenesis in humans. AB - It has been hypothesized that bacterially produced N-nitroso compounds cause the progression from chronic atrophic gastritis through intestinal metaplasia and dysplasia to gastric cancer. If this is true then various consequences follow. These consequences are discussed, together with the evidence for or against them. The conclusion is that there is much to support the hypothesis. PMID- 1747497 TI - Cell proliferation kinetics as a marker of gastric cancer risk. AB - Although cell proliferation studies on gastric mucosa are relatively few compared to the results obtained in the large bowel, they brought important contributions to our knowledge of the mechanisms involved in the development and progression of neoplasia. In normal gastric mucosa, the proliferative zone is limited to the neck region of the glands. In diseases at risk for gastric cancer, such as chronic atrophic gastritis, two main features have been observed: an increased cell proliferation rate and expansion or upward displacement of the proliferative compartment. However, while a high cell turnover rate can be due to many stimuli such as inflammation or the effect of hormones (i. e. gastrin), the expansion of the proliferative compartment is more evident with the development and progression of neoplasia. It could be due to an error in the control of cell proliferation and maturation. This kinetic pattern is probably a marker of gastric cancer risk. Application of these observations in clinical investigations are the search for proliferative abnormalities and other phenotypical markers in order to define an individual profile of cancer risk, and to evaluate the effects of xenobiotics or dietary intervention in controlled trials. PMID- 1747498 TI - Liver transplantation for chronic viral hepatitis. AB - Liver transplantation remains a problem for end stage liver disease due to chronic viral hepatitis, in contrast to the success with fulminant hepatitis B, D and C in which recurrence of viraemia is relatively rare. Following transplantation for chronic HCV disease recurrence of hepatitis C is infrequent and does not appear to be an important clinical problem. The complete picture will only be described when a suitable HCV-RNA test becomes routinely available. Patients with cirrhosis due to hepatitis B, with low levels of viraemia, or patients with hepatitis D are less likely to develop reinfection than those with high levels of HBV viraemia. The use of hepatitis B immunoglobulin in high doses for prolonged periods delays rather than prevents recurrence. It is a very expensive ancillary treatment. Patients with chronic hepatitis D related cirrhosis in whom levels of hepatitis B replication are suppressed, have a low recurrence rate even without immunoglobulin prophylaxis although HDAg remains in the liver. Hepatitis only reoccurs with recurrence of HBV infection. Unfortunately transplantation of HBV DNA and HBeAg positive patients has many shortcomings, and reinfection of the engrafted liver and subsequent development of hepatitis B is common. Survival rates are reduced in this latter group. At present there are no firm recommendations that can be given to prevent recurrence: HBIG in large doses and for prolonged periods would appear to be insufficient to prevent reinfection and these patients often die of recurrent disease. A major challenge for transplant groups will be the prevention of viral reinfection particularly in this latter group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747499 TI - Liver cirrhosis in Italy. A multicentre study on presenting modalities and the impact on health care resources. National Project on Liver Cirrhosis Group. AB - A cross-sectional multicentric study was carried out over a six-month period as part of the "Progetto Nazionale Cirrosi Epatica", in order to update information about: a) the prevalence of different aetiologic factors and various nosological varieties of cirrhosis in Italy, as well as its presenting modalities; b) the currently used approach either to the diagnosis or the treatment of complications of cirrhosis; c) the impact of liver cirrhosis on medical care in terms of number of hospitalizations and length of hospital stay, instrumental procedures and management, and d) the size of patient's population referred to the participating centers, in order to help design further studies. From February 1st through July 31st 1987, 1,386 forms relative to 1,101 patients were collected. In 320 patients the diagnosis of cirrhosis was first made during the investigation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747500 TI - Mycobacteria and subgroups of patients in Crohn's disease. AB - Some recent studies have proposed a subclassification of Crohn's Disease (CD) on the basis of the pathological picture. In fact CD is a heterogeneous disease, and it is probable that the clinical and pathological disorders we now consider as CD may in the near future be divided into several conditions, probably with different causes as well, including environmental factors. Clinical and pathological similarities to mycobacterial disease, along with recent isolation of mycobacteria from tissues taken from patients with CD, and the recognition of atypical mycobacteria as causative agents of an enteritis pathologically similar to CD, all go to strengthen the hypothesis that these organisms are one of the above environmental factors. Researchers should therefore seek to identify and characterize this subgroup of CD patients who may have mycobacterial disease and to perform trials of antimycobacterial therapy. Analysis of the literature gives some suggestions for identifying this subgroup of patients: i) isolation of atypical mycobacteria from the tissues; ii) presence of high specific antibody levels and increase of same after antimycobacterial therapy; iii) presence of granulomas, and iv) strong suspicion of an environmental factor. PMID- 1747501 TI - Omeprazole vs. ranitidine in short-term treatment of Helicobacter pylori positive duodenal ulcer patients. AB - Forty-three patients with active duodenal ulcer and Helicobacter pylori positivity in gastric antrum were randomly assigned to either omeprazole treatment (20 mg once a day) or ranitidine treatment (300 mg once a day) for 28 days. Re-evaluation of the patients (clinical and endoscopic examination and assessments for H pylori detection) was repeated after 2 weeks and at the end of the treatment. Healing rates in the omeprazole group were 40% after 2 weeks and 90% after 4 weeks, in the ranitidine group ulcer healing was recorded in 20% of patients after 2 weeks and in 80% after 4 weeks. Differences between treatments at 2 and 4 weeks were not statistically significant. Clinical response (disappearance of ulcer-related symptoms) was better in the omeprazole group at 2 weeks (p less than 0.05) but not at 4 weeks. At the end of the trial H pylori positivity in gastric antrum disappeared in 95% of the patients treated with omeprazole and in 5% of the patients who received ranitidine (p less than 0.001). The results confirm the effectiveness of omeprazole in short-term treatment of duodenal ulcer and re-emphasize the powerful activity of the drug on H pylori infection. PMID- 1747502 TI - What is new on cancer research. PMID- 1747503 TI - Role of sulphydryl compounds in the defense of rat gastric epithelial cells against oxygen reactive metabolite-induced damage. AB - This study evaluated the role of endogenous and exogenous sulphydryl compounds in the defense of rat gastric epithelial cells against damage brought about by oxygen reactive metabolites in vitro. Toxic oxygen species were generated by xanthine oxidase in the presence of xanthine. Cell damage was assessed by 51 chromium release assay. Our data confirm that xanthine oxidase, in the presence of xanthine damages cultured rat gastric cells in a dose dependent manner (r = 0.0885, p less than 0.05). Depletion of endogenous thiols by N-ethylmaleimide significantly increases the amount of damage induced by oxygen radicals causing, at the concentration of 0.005 mM, a 60% increase in 51 chromium release (p less than 0.001). The sulphydryl agent cysteamine did not prevent cell damage induced by oxygen reactive metabolites. In conclusion, 1) depletion of endogenous thiols significantly increases the susceptibility of rat gastric epithelial cells to oxygen radical-induced damage; 2) this damage is not prevented by an exogenous agent containing a SH group. PMID- 1747504 TI - Investigations on caffeine passage into the canine gastric juice. AB - Two caffeine boluses (5 and 10 mg/kg) were i.v. administered to four gastric fistula dogs. Gastric secretion was collected before and during pentagastrin stimulation (1, 2 and 4 micrograms/kg/h). Caffeine concentration in serum and gastric juice was determined by HPLC. Mean serum caffeine concentrations were clearly dose-dependent: 4.88 +/- 0.73 (n = 72) and 10.18 +/- 0.98 mg/l (n = 70). After each bolus, the time course of serum concentration was described by a single exponential, yielding an estimation of caffeine half-life: 310 +/- 46 (n = 9) and 453 +/- 59 min (n = 9), respectively. In both cases the same apparent volume of distribution: 0.87 +/- 0.02 l/kg (n = 9) was found. In gastric juice, caffeine concentration depended on the caffeine dose: 2.51 +/- 2.15 (n = 66) and 6.04 +/- 2.57 mg/l (n = 62); outputs were found to be linearly related to juice output, the slope being controlled by the caffeine dose. It was concluded that caffeine passage into gastric juice was governed by a solvent drag mechanism. PMID- 1747505 TI - Famotidine vs ranitidine h.s. in acute duodenal ulcer. A multicentre endoscopic trial. AB - A double-blind, randomized, active drug-controlled study was conducted in order to evaluate the efficacy and safety of famotidine vs ranitidine h.s. in promoting the healing of acute duodenal ulcers. Two hundred and eighty patients participated in the trial and received either famotidine 40mg h.s. or ranitidine, 300mg h.s. The two groups were not significantly different with regard to sex and risk factors such as alcohol consumption and family history of peptic ulcer disease, while in the famotidine group, there was a slightly higher number of patients who smoked. Endoscopy was performed at the end of 4 and 6 weeks in 248 patients (128 in the famotidine group and 120 in the ranitidine group). The healing rate in those receiving famotidine was 73.4% at the end of 4 weeks and increased to 93% at the end of 6 weeks, while in the ranitidine group, the rate was 75.8% and 92.5% respectively. Day and night pain markedly reduced in both groups and therapy was generally well tolerated. PMID- 1747506 TI - Epithelial dysplasia in atrophic gastritis. Bioptical follow-up study. AB - Fifty-nine cases of gastric dysplasia (46 of which were mild, 11 moderate and 2 severe) were studied in relation to their association with atrophic gastritis and intestinal metaplasia. Atrophic gastritis was found in 39 cases (28 of which were mild, 10 moderate and 1 severe). Dysplasia was considered "persistent" when found of the same degree in at least two consecutive check-ups after initial diagnosis (13 cases); it was considered "progressive" if found more severe or evolving as cancer (5 cases) or "regressive" if detected in a lesser degree or no longer detected (13 cases). Sixteen of the 18 persistent or progressive cases of dysplasia were associated with atrophic gastritis, whereas 10 of the 13 cases with regressive dysplasia revealed no concomitant pattern of gastric mucosa atrophy (p less than 0.005). These findings suggest that dysplasia represents a truly pre-neoplastic change particularly when associated with atrophic gastritis and which must therefore be more carefully monitored. PMID- 1747507 TI - Effect of physical exercise on one-sample antipyrine clearance. AB - Moderate physical exercise for a few hours is not expected to reduce the hepatic elimination of drugs exhibiting capacity-limited metabolism (low-clearance drugs such as antipyrine). However, previous studies have shown that antipyrine half life, measured by the multiple-sampling technique, is increased by exercise. A simplified one-sample procedure for antipyrine clearance determination is increasingly being used as a liver function test. The effects of exercise on this measurement have never been evaluated. We measured antipyrine clearance, using the one-sample, simplified procedure in a group of 50 young Italian army soldiers, while at rest and during a 6 hour march in the mountains (extra energy expenditure: 7.43 kjoule per min). Mean antipyrine clearance was on average 46.6 (SD 10.2) ml/min (range 30.5-65.4) while resting, and 46.2 (10.5) (range 25.5 64.8) while exercising (not different). No specific advice regarding physical exercise is needed whenever liver function is measured in outpatients by the one sample, simplified antipyrine clearance test. PMID- 1747508 TI - Abdominal ultrasonography in the diagnosis of extrinsic endoscopic compressions of stomach and duodenum. AB - Extrinsic compressions of stomach or duodenum (ECSD) are occasionally found during endoscopic examination. Ultrasonography is usually performed in order to explain the significance of this feature. We have prospectively assessed the prevalence of ECSD and the diagnostic role of US in this context. ECSD were found in 37 out of 6604 gastroduodenoscopies. An abdominal US was performed after endoscopy in all these patients. The extrinsic compressions were in the gastric anterior wall in 7 patients in the gastric posterior wall in 10 patients, and in the lesser curvature in 9 patients and in the duodenum in 11 patients. In 20 patients the compression was due to neoplastic lesions, in another 15 non neoplastic conditions were found (hepatomegaly, splenomegaly, gallbladder hydrops, pancreatic pseudocyst, vascular malformations). Ultrasonography was demonstrated to have an elevated sensitivity (87.5%) and an elevated specificity (100%) when technically adequate. We conclude that extrinsic compressions of stomach and duodenum detected at endoscopy are frequently associated to neoplastic lesions. Abdominal ultrasonography is an accurate tool, when technically adequate, as an initial screening test for such lesions. Endosonography, CT scan or other invasive tests must be performed in doubtful cases. PMID- 1747509 TI - Eosinophilic gastroenteritis: report of two atypical cases. AB - Eosinophilic Gastroenteritis (EG) is a poorly understood disorder defined by eosinophilic infiltration of the bowel wall, eosinophilia and gastrointestinal symptoms. The disease's aetiology, course and treatment are not well known. We report two atypical cases of EG: one involving the mucosal layer and another involving the serosal and muscularis layer. The first shows how EG may present with a long history of episodes of intestinal obstruction and malabsorption and how the disease could take a severe course and may be unresponsive to treatment. The second case shows EG presenting as acute abdomen and which subsequently became asymptomatic without therapy, regardless of the fact that peripheral eosinophilia remained present. This case raises the problem of how to treat an asymptomatic patient, what parameters should be considered in order to assess the progress of the disease and the indications for treatment. PMID- 1747510 TI - Gastrospirillum Hominis associated chronic active gastritis: the first report from Italy. AB - Recently a spiral bacterium different from Helicobacter Pylori (HP) was observed in the human stomach and the name of Gastrospirillum Hominis (GH) was proposed for this organism. GH presence is reported to be not associated to HP but related to chronic active gastritis. We describe the case of a 31 year old male suffering from upper abdominal symptoms, who underwent oesophagogastroduodenoscopy, which revealed a picture of duodenal hyperemia. Gastric body showed a normal mucosa and absence of HP, while active chronic gastritis associated with HP was found in the antrum. In addition few spiral bacteria showing 4-5 spirals, larger than HP were observed within the gastric crypts and beneath the mucus layer in this site. This case represents the first report from our geographic area (Southern Italy) of the possibility of finding bacteria different from HP in the human stomach. The simultaneous HP presence does not allow us to relate the chronic active gastritis of the patient with the GH like bacteria. Our finding, however, suggests the possibility that HP and GH may be simultaneously present in the course of type B antral chronic inflammation. This association was not observed in previous investigations. PMID- 1747511 TI - Acquired factor VIII inhibitor in a patient with adenocarcinoma of the colon rectum. AB - The presence of a circulating inhibitor of factor VIII was observed and described in several pathological conditions. In the present study we describe the case of a patient with a severe haemorrhagic syndrome caused by the presence of a circulating inhibitor of factor VIII discovered following abdominal surgery for an adenocarcinoma of the colon rectum. The haemorrhagic syndrome evolved independently from the course of the neoplastic disease. PMID- 1747512 TI - Iatrogenic haemobilia: ultrasound appearance of intragallbladder haemorrhage. A report of two cases. AB - Ultrasound appearance of intragallbladder haemorrhage in two patients with haemobilia is presented. Gallbladder lumina were occupied by non-shadowing, firm masses of mixed echogenicity representing blood clots. In both cases iatrogenic trauma following percutaneous transcholecystic cholangiography and blind hepatic biopsy caused bleeding in the biliary tree. PMID- 1747513 TI - Sensory nerves in the gastrointestinal tract: changing concepts and new perspectives. AB - In recent years great interest has been directed to study the function of capsaicin-sensitive primary afferents in the gastrointestinal tract. It has been demonstrated that these fibers not only have a sensory role but also play a local efferent function through direct and indirect effects of released neurotransmitters. Peptides released by capsaicin-sensitive nerves are involved in several functions modulating either the local blood flow or the gastrointestinal motility. The analysis of the action of released transmitters may serve to understand the physiology and pathophysiology of the gastrointestinal tract. All data here reported demonstrate that the study of capsaicin-sensitive primary afferents may be helpful to develop new pharmacological treatment of various human disease of the gastrointestinal tract. PMID- 1747514 TI - [Public health in very low fertility era]. PMID- 1747515 TI - [A review on mental health and psychiatric services in England]. AB - Psychiatric care in Japan has received criticism not only within Japan but from other parts of the world. By contrast, the services for mentally ill in England is considered to be superior and is therefore presented briefly to benefit the development of better community psychiatric care in Japan. The history of psychiatric services in England is described briefly. After World War II, deinstitutionalization has been occurring and the in-patient rate per 100,000 population which was 354 in 1954 and has decreased to 120 in 1990. Despite a decrease in the in-patient rate, the admission rate per 100,000 population has been increasing gradually during this period. Deinstitutionalization process and the development of community care services are summarized. Among these are alternative services such as primary care, day care and residential services in the community which are considered to be important elements. Problems associated with deinstitutionalization process are also discussed. In developing community care services in Japan, lessons can be learned from the success and failures of England's attempt over the last 30-years to build a better, more community-based system. PMID- 1747516 TI - [Relationship of self-rated health to mortality among the community elderly]. AB - The purpose of the present study is to examine the relationship of self-rated health to mortality. Subjects consisted of 1096 elderly (471 men, 625 women) aged 65 years and over in 1983, living in the town of Yuwa in Akita Prefecture. They were followed to determine survivorship status and relocation for 7 years after the baseline survey in 1983. The relationship of self-rated health to mortality was tested using a logistic model. The results obtained were as follows: (1) Poor self-rated health was significantly related to higher mortality in a graded fashion by univariate analyses. (2) The significant relationship of self-rated health to mortality was still observed after controlling for sex, age, education, drinking, smoking, physician visits, history of stroke, and activities of daily living. (3) The contribution of self-rated health to mortality differed by sex, age group (65-74, 75-), and period of follow-up (early, late). The contribution was greater in men, aged 75 and over, and during the latter part of the follow up. PMID- 1747517 TI - [A population based epidemiological study of senile cataracts]. AB - A population based study on senile cataracts was conducted on 295 participants in an ophthalmologic examination in a rural area of Ishikawa prefecture. Subjects were above 40 years of age and received an ophthalmologic examination and were personally interviewed. The following results were obtained. 1) Prevalence of senile cataracts increased with age. 2) For eyes with lens opacity grade III 66.3% showed a visual acuity below 0.7, while about 45% with lens opacity grade I or II was a visual acuity below 0.7. 3) Among those determined to have senile cataracts by this study the proportion with a prior diagnosis of senile cataracts was low, i.e., 36% even in advanced cataracts with lens opacity grade III. The proportion improved with worsened visual acuity and having a personal ophthalmologist. 4) Of those already diagnosed with senile cataracts, 56.7% failed to visit an eye specialist after than. This proportion tended to be lower in persons with worsened visual acuity. 5) About a half of those who continued to visit an eye doctor utilized anti-cataract medication. 6) The level of knowledge regarding senile cataracts was statistically lower with age. PMID- 1747518 TI - [Effect of intensive vacuum cleaning in reducing house dust mite antigen in bed rooms of asthmatic children]. AB - House dust mite (Dermatophagoides farinae) antigen was measured by enzyme-linked immunosorbent assay in house dust samples obtained from the bed rooms of asthmatic children and normal controls. In 37 rooms where regular vacuum cleaning was performed, the mean of D.f. antigen was 4.42 +/- 7.55 micrograms/m2. In the 24 bed rooms of asthmatic children, mean levels of D.f. antigen decreased significantly (p less than 0.05) after intensive cleaning (systematic cleaning) was continued for 4 weeks (0.78 +/- 0.93 micrograms/m2) compared to prior to initiation of systematic cleaning (4.12 +/- 6.31 micrograms/m2). Symptom scores decreased in 65% of the asthmatic children. In 8 bed rooms of normal controls, mean levels of D.f. antigen also showed a decrease after systematic cleaning (0.43 +/- 0.62 micrograms/m2) compared to before (5.59 +/- 12.46 micrograms/m2). However there was no significant difference in D.f. antigen between the bed rooms of asthmatic children and normal controls. Intensive cleaning markedly decreased the allergen in both groups, clearly suggesting effectiveness in the reduction of asthmatic attacks in patients and perhaps also in preventing sensitization of healthy children. PMID- 1747519 TI - [Studies on the dynamics of Salmonella organisms in raw sewage treatment plants]. AB - The dynamics of Salmonella organisms in raw sewage treatment plants was studied over a period from July 1987 to August 1989. An experiment where Salmonella ser. Havana NAr was introduced into raw sewage was also performed over 2 days during this period. The results are as follows. 1) A number of strains of Salmonella could be isolated usually from samples drawn from raw sewage influent and up to the activated sludge stage of sewage processing. 2) After Salmonella ser. Havana NAr was introduced into raw sewage, the number of the organisms decreased in the activated sludge process to 1/1000 and the organisms were not found in the treatment plants after about forty days. 3) These results suggest that Salmonellas are adsorbed to activated sludge or other sludges, and are not discharged into rivers from this treatment plant. 4) The possibility of being able to determine the strain of Salmonella in regional epidemics by serovars of Salmonella detected in raw sewage treatment plants was suggested. PMID- 1747520 TI - [Isolation of Yersinia, campylobacter, Plesiomonas and Aeromonas from environmental water and fresh water fishes]. AB - Yersinia, Campylobacter, Plesiomonas and Aeromonas are known causative agents in waterborne diseases. For about 10 years, outbreak of diarrhea has been observed, especially among children, in the mountain areas of Okayama. Y. pseudotuberculosis recently isolated from non-chlorinated drinking water sources such as mountain streams and wells has been suspected to be the causative bacteria of the disease. Attempts were made to isolate Yersinia and Campylobacter from water samples from rivers in rural areas and Plesiomonas and Aeromonas from samples of well water and fresh water fishes in Okayama prefecture from 1987 to 1990. The isolation rate of Yersinia from river water samples was 7.5% with a higher rate in the mountain areas than in the nonmountain areas. While Y. enterocolitica was isolated throughout the year, Y. pseudotuberculosis was only seen during the winter. Various serogroups including human types of Y. enterocolitica and serogroup 2B, 4A and UT of Y. pseudotuberculosis were detected. Campylobacter was isolated from 0.5% of river water samples. Plesiomonas from 1.5% of fresh water fishes, and Aeromonas was isolated from 6.9% of well water samples and 47.1% of fresh water fishes. PMID- 1747521 TI - [Tuberculosis epidemic in a mental hospital]. PMID- 1747522 TI - [Japan's official development assistance in medicine and public health]. PMID- 1747523 TI - [Mental and physical condition group characteristics of disabled elderly living at home and principal diseases related to them]. AB - A survival study over a period of one thousand days from July 1985 was performed on 177 cases of disabled elderly (aged 65 and over) living in Moriguchi-city, Osaka, who were enrolled as recipients of solatia for the disabled elderly. At the start of this study, subjects or family members were questioned regarding physical and mental status, clinical history and social environment of these elderly and their family. On the basis of these findings, the level of disability of the elderly was estimated by applying scores to identify physical and mental conditions: The score on physical status, named Total Functional Capacity (TFC), is equivalent to the dependent level of ADL: mental status was scored by assessing seven typical psychiatric questions relating to dementia (Mental Status Score: (MSS]. The following findings were obtained. 1) It was confirmed that mortality probability tended to increase by degrees in proportion to lower level of independent ADL which was indicated by high scores of TFC, and a greater number of psychiatric symptoms such as often observed in the case of dementia (i.e. high scores of MSS) in either sex. 2) For males, among the major diseases precipitating disability, the proportion for stroke was about 50%. In females, disability causes were distribute into various categories of diseases, but orthopedic diseases (e.g. accident or a fracture), contributed a large proportion. The percentage of elderly who became disabled due to stroke was higher in the lower age categories for females. 3) TFC scores did not correlate with age among either sex. 4) More than 40% had more than one psychiatric symptom included in the MSS score. The proportion of elderly having any one symptom tended to increase with age for either sex, and was especially significant for females. 5) Correlation was seen between TFC and MSS for only female. PMID- 1747524 TI - [The relationship of chewing ability to nutrient and food intakes in the community elderly]. AB - The purpose of the present study is to investigate the relationship of chewing ability to nutrient and food intakes in the community elderly. Subjects consisted of 145 elderly residents (56 males, 89 females) ranging in age from 65 to 79 years, living at home in a village of Okinawa Prefecture. Chewing ability was divided into two categories: being able to chew ordinary foods was defined as "good", and being able to chew only soft foods as "bad". To determine quantitative food intakes 24-hour dietary records were utilized which were confirmed by nutritionists during interviews. Good chewing ability was found in 82.1% for males and 83.1% for females with no statistically significant difference concerning age or sex. Teeth status was significantly related to chewing ability. For both males and females, protein intake was lower in the group with bad chewing ability than in the good group. Only in males intakes of total energy, fats, Ca, and Fe were lower in the group with bad chewing ability. Concerning food items, intakes of dark green and yellow vegetables and fat in males, and intake of rice in females, were lower in the group with bad chewing ability. PMID- 1747525 TI - [Standardization of definitions concerning smoking behavior among Japanese adolescents--results from the Japan Adolescent Smoking Survey (JASS)]. AB - The aim of the Japan Adolescent Smoking Survey (JASS) is to standardize the definitions of smoking behavior among Japanese adolescents together with measurement methods and questionnaires concerned. A study of 9921 school children aged 9 to 18 years in 17 elementary schools, 16 junior high schools and 18 senior high schools in 9 prefectures, was conducted between June and July of 1989, to determine the relationship between actual smoking behavior during the past month or year and the "self-referent label" concerning their smoking status. The main results were as follows: 1) The percentage of those who smoked at least one cigarette during the past month showed a high degree of similarity to the percentage of those who referred to themselves as "regular smokers" or "occasional smokers". 2) Less than 10% of students who identified themselves as "never smokers" or "ex-smokers" smoked at least one cigarette during the past month, while more than 80% of students who referred to themselves as "regular smokers" or "occasional smokers" smoked during the past month. 3) On the whole, those who smoked 20 or more cigarettes during the past month referred to themselves as "regular smokers"; those who smoked between 2 and 19 cigarettes as "occasional smokers"; those who smoked 1 cigarette as "ex-smokers"; those who did not smoke during the past month as "never smokers". 4) The definition where students who smoked one cigarette during the past month are classified as a category of smoker, displayed a high level of sensitivity and specificity for all school-level groups and for both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747526 TI - [Survey on international health related education in preventive medicine curricula of medical school in Japan]. AB - A nation-wide survey of the 150 active members of the Japan Association of the Directors of the Departments of Hygiene and Public Health at Medical Schools (80 medical schools) in Japan was conducted regarding international health related education for the 1990 academic year. The survey questionnaire used 6 basic questions, including some space for free answers. There were 105 effective responses (70.0%). Among them 61 answered that educational courses related to international health were provided in their curriculum; 16 out of 39 (41.0%) in the department of hygiene, 34 out of 48 (70.8%) in the department of public health, and 11 out of 18 (61.1%) in others. However, there were 24 that had the same title of "International Health". The most prevalent key-word was WHO (41), with international exchange and cooperation (15), JICA (14), PHC (12), ILO (12) following in that order. These results suggest a need for curriculum improvement in the near future for implementing international health education. Some strategies for developing international health related education in the broader context of the whole medical curriculum in collaboration with other departments are discussed. PMID- 1747527 TI - [Survey on international health related education in the schools of public health nurses in Japan]. AB - A nation-wide survey of directors of 60 schools for public health nurse education in Japan was made from April and May of 1990 regarding international health related education for the 1990 academic year. The survey questionnaire utilized 3 questions, and a column for free answers. An effective response rate of 76.7% from a total of 46 schools was obtained: 4 year colleges-4; 3 year junior colleges-4; and 37 schools with a 1 year course. Among them 27 schools (67.9%) responded that related courses was available in their curriculum. Except for 2 key-words (WHO, Alma-Ata Declaration-PHC) which are found in all schools, quarantineable diseases were taught in 34 schools, international exchange and cooperation in 23, JICA (Japan International Cooperation Agency) in 10, NGO in 10, health care for the Japanese in foreign countries in 6. Free answers were provided by 22 schools. From these results, the need for a changing role of the public health nurses in the internationalizing of Japan's society and for future curriculum development is seen. PMID- 1747528 TI - [A method of interval estimation for number of patients in the nationwide epidemiological survey on intractable diseases]. AB - A method for estimating the intervals for the number of patients with intractable diseases from nationwide epidemiological surveys was developed under the assumption that response is independent of frequency of patients. This method is based on data utilizing the number of response hospitals classified by their reported number of patients. The approximate 95% confidence intervals of numbers of several intractable diseases patients were estimated using this method. PMID- 1747529 TI - [Measures for problems concerning community dental health plan]. PMID- 1747530 TI - [Seasonal variation of mortality from cerebro-cardiovascular diseases--effect of ambient temperature on death]. AB - A study to clarify the relationship between seasonal variations in mortality from cerebro-cardiovascular diseases and ambient temperature (maximum/minimum temperature and daily range) was performed using time series analysis, and the role of ambient temperature as an associated factor in cerebro-cardiovascular disease caused death was discussed. The following results were obtained: 1) The seasonality factor associated with the monthly variation for mortality was of greater magnitude for heart diseases more than for cerebral diseases. There was a tendency for mortality from cardiac diseases to decline gradually from February/March to July/August, and to increase in October/November, with a maximum peak in the curve of seasonal variation observed in January/February. 2) The seasonal factor associated with maximum/minimum temperature and daily temperature range showed a stable variation in magnitude from January to December, with temperatures displaying a single peak in August. Daily temperature range was lowest during summer and highest during the late fall, winter or early spring. 3) A statistically significant negative correlation was seen between mortality from cerebro-cardiovascular diseases and seasonality and temperature, while a positive correlation was seen between mortality and daily temperature range, suggesting that low environmental temperatures may operate indirectly as a factor that affects cerebro-cardiovascular disease mortality. PMID- 1747531 TI - [Clustering of suicides under age 20--seasonal trends and the influence of newspaper reports]. AB - The existence of temporal clustering of suicides was analyzed by comparing the distribution of weekly numbers of suicides under age 20 in Japan (1982-1987) with a Poisson distribution. The linkage between newspaper reports about teenage suicides and these clusters of suicides was examined in an ecologic study. The following results were obtained: 1) The distribution of weekly numbers of suicides under age 20 was not consistent with a Poisson distribution. The observed numbers for weeks with clustering was higher than the expected numbers. Therefore it is suspected that teenage suicides was not an independent occurrence but clustered in specific weeks with clustering observed in April and between the 15th and 25th weeks in 1986. 2) The age and sex characteristics of those who committed suicide during the observed clusters every April did not differ from that of suicide victims for the rest of the year. The incidence ratio for suicide between 15th and 25th weeks in 1986 compared to the same period for other years was higher in girls than in boys, and higher in younger teenagers than older teenagers. Analysis by prefecture of suicides which occurred between the 15th and 25th weeks in 1986 showed high incidences for Hokkaido, Tohoku, Chugoku, and Shikoku blocks, and low incidences for the Kanto and Kinki blocks. 3) Twenty news articles reporting teenage suicides with headings much larger than four columns appeared in the Asahi Newspaper in 1982-87. Significant linkage between newspaper reports about teenage suicides and trend of weekly numbers of suicides in 1985 and 1986 was not observed. 4) Weekly numbers of suicides significantly increased following newspaper reports on January 23rd 1985 and on April 8th 1986, describing a suicide caused by battering, and a jumping suicide of a young singer who was popular among teenagers, respectively. However no increase in the number of suicides was observed following other newspaper reports. PMID- 1747532 TI - [Subjective health and related factors among middle-aged men living in Tokyo--a comparative study]. AB - Random samples of middle-aged (35-64) male residents of two different areas in Tokyo, Bunkyo-ku, a low-mortality area (n = 767) and Koto-ku a high mortality area (n = 790) were interviewed between March and April in 1988, concerning health and life style. The two populations were compared regarding, 1) health status which was examined from the view point of fatigue, symptoms and self-rated health, 2) factors related to the three health indices. The main results were as follows: 1. No significant differences were seen between the two populations in the gross means for health indices. However when the health indices were stratified by age group, mental fatigue and minor symptoms were more prevalent in Bunkyo-ku than Koto-ku among young people, while prevalence of physical fatigue and major symptoms was higher in Koto-ku among old people. 2. The relationship between the health indices and job type, income, education and marital status was examined. In Bunkyo-ku, no relationship was seen after controlling for age, working conditions and life style. On the other hand, in Koto-ku, significant relationships were seen with age, job type and marital status, and health problems were prevalent not only among those with low socioeconomic status but also in other socioeconomic groups. These results were maintained even after controlling for age, working conditions and life style, similar to the analysis for Bunkyo-ku, indicating that health problems in this population do not appear to be solely the result of working conditions or life style. PMID- 1747533 TI - [A cohort study on deaths from SMON in Japan]. AB - Causes and risk factors of deaths from subacute myelo-optico neuropathy (SMON) were studied in a prospective cohort of 4,329 SMON patients followed for 3 years and 7 months (Sept. 1985-March 1989) with the following findings: (1) Recent excess deaths of SMON patients was estimated as 4% from ratio of O/E (SMR = 104) and deaths due to SMON itself was 6.4%. (2) The ratio of O/E was significantly higher for deaths from cancer of colon/rectum in females, cancer of pancreas in males, hypertension in males, pneumonia/influenza in females, chronic obstructive pulmonary diseases in males, tuberculosis and intestinal obstructive disease in males and females. (3) The ratio of O/E was 1.8 times or greater for those SMON patients with complications of cerebrovascular disease, severe blindness, complete loss of ambulation, and who were bedridden, and who are unable to receive home care from family members or trained home helpers. PMID- 1747534 TI - [Trends in length of stay of psychiatric inpatients based on "patient survey"]. AB - The average length of occupancy for psychiatric beds in Japan has been pointed out to be among the longest in the world. However, neither the average length of occupancy since admission of psychiatric resident patients present at a facility at a given point of time (e.g. at the end of every October) nor the average length of stay of psychiatric patients until discharge have been reported in national health statistics. Using data from the "Patient Survey (1974-1984, 1987)" by the Ministry of Health and Welfare, estimates of trends for 1) length of hospitalization since admission of resident patients at the end of every October and 2) length of hospital stay from admission to discharge in patient cohorts admitted each year from 1974 to 1984, were determined. A remarkable difference in distribution was observed in the length of hospitalization in psychiatric residents and length of stay until discharge. For psychiatric residents surveyed at the end of October 1987, 13% had been resident for less than 3 months, 27% within one year, and 54% within 5 years. On the other hand, 33% of the patient cohort admitted in 1984 were discharged within one month, 59% within 3 months, and 85% within one year. Six percent of the cohort, however, had remained hospitalized for more than 3 years, some of whom were potential 'new' long-stay patients. The proportion of patients staying more than ten years shows an increase from 17% in 1974 to 30% in 1987, with the distribution of length of hospitalization in residents demonstrating a definite shift to increased length. On the other hand, length of stay until discharge shows a slight shortening. PMID- 1747535 TI - [Fatty acid composition of foods (report 2)--substituted dairy products]. PMID- 1747536 TI - [Risk evaluation of changes in global environment on human health]. PMID- 1747537 TI - [Survey of attitudes among general practitioners regarding the introduction of a personal computer medical network system in community health care]. AB - General practitioners (GPs) play an important part in community health care. Their opinion regarding introduction of a medical information network system using a personal computer and factors influencing the decision to introduce such a system were surveyed among 977 randomly sampled GPs. A response from 727 GPs was obtained. Based on a two stage selection method, 20 factors were selected as effective factors among the 73 factors surveyed, with the following results: (1) Responses to the question concerning the approval of system introduction were classified into three groups: "not necessary + too early to make a decision (DA)" (DA group), "approve (A)" (A group) and "undecided (UD)" (UD group). Each group had nearly equal numbers of respondees. (2) Significant effective factors were "experience with personal computers", "a desire to use a personal computer", "a desire to use a computer-diagnosis-system", "cost", and "a volition to operate a computer by himself". (3) The "A group" had high experience and affirmative opinions, while the "DA group" had low experience and negative opinions. The "UD group" also tended to respond with "do not know" regarding the factors. (4) Approval of system introduction requires providing basic knowledge on computers, opportunities for positive experience with computers, and practical examples of problem solutions in a general practitioner's work. PMID- 1747538 TI - [Evaluation of methods for measuring daily physical activity in terms of energy expenditure]. AB - Various methods exist for measuring daily physical activity and daily energy expenditure and daily pedometer readings are most commonly used for the amount of physical activity. In this study, three methods for measuring energy expenditure 24-hr heart rate method (HR), time study method, and caloric expenditure accumulator (CC)-, and the feasibility of a pedometer for the assessment of energy expenditure were examined under laboratory conditions and during normal daily life. Daily physical activity was measured by four methods (HR, Time study, CC, Pedometer) in a field study of 14 young, healthy and sedentary women, and compared. Laboratory validation of the three methods with measurement of oxygen uptake was performed with 5 young men and 1 woman walking and running at different speeds and grades on a treadmill. In addition validation tests of whether pedometer readings reflect differences in energy expenditure due to speed and grade and whether pedometer counts steps exactly were also conducted. The 24 hr energy expenditure derived from CC was significantly lower than that derived from HR and Time study, due to lower estimation of energy expenditure from activities compared to other methods. In the laboratory study, the energy expenditure measured at 5% grade was low by CC and differences in energy expenditure for changes in grade could not be differentiated. Time study revealed a significant relationship between CC and HR in field study. These results suggest that CC tends to underestimate the 24-hr energy expenditure from activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747539 TI - [Cigarette smoking and mortality among Japanese males in a prospective cohort study]. AB - The relationship between smoking and disease was studied in a prospective cohort study among a Japanese male working population. The relative risk of cigarette smoking was positively associated with mortality for all diseases and major neoplasms. In current smokers consuming 25 to 34 cigarettes per day, relative risk for all diseases, major neoplasms, and lung cancer compared to nonsmokers was 1.38, 2.04, 2.36, respectively. These data suggest that there is a positive relation between smoking and disease mortality in this male working population. As for ex-smokers, estimated relative risk for all neoplasms was between that of current smokers and nonsmokers. PMID- 1747540 TI - [A study of dental status and its contributing factors in mentally retarded persons institutionalized in welfare facilities]. AB - Two hundred and forty-one mentally retarded persons, institutionalized in three private welfare facilities in Oita Prefecture, were assessed for dental status and tooth brushing ability. Information on their life style was also obtained by a questionnaire completed by their supervisors in the facilities. 1) Dental status of mentally retarded subjects was found to be inferior compared to the general Japanese population studied in the survey of dental disease in 1987 by the Ministry of Health and Welfare. Inferior dental status was characterized by a low score for filled teeth and a high score for missing teeth. 2) Both low tooth brushing ability and low intelligence quotient were associated with their poor dental status. 3) Discrepancy between supervisor assessment of tooth brushing ability and actual ability was observed. 4) Periodontitis was observed in young epileptics taking antiepileptic medication at a high rate. However there was no association between the taking of antiepileptic medication and missing teeth score. These results indicate a necessity for more active dental services including the teaching of tooth brushing and early treatment by dentists and supervisors. PMID- 1747541 TI - [Mutagenicity of rice-straw and -husk ashes by Ames test]. AB - In the rice-producing district of Japan, environmental pollution by smoke from burnt rice straws has become a matter of concern. The mutagenicity of fly- and bottom-ashes of rice-straw and -husk was assayed by the Ames test, TA100 +/- S9 and TA98 +/- S9, and the relationship of combustion temperature to mutagenicity was investigated. Fly ash showed weak mutagenicity at 300 degrees C, with no remarkable change in mutagenic activity between 300 degrees C and 500 degrees C. Above 500 degrees C the mutagenic activity increased with a rise of temperature. The increasing rate of mutagenicity was much higher in the test system with S9 mix than that without S9. Moreover, the mutagenicity with TA100 was stronger than with TA98. With respect to bottom ash, weak mutagenic activity was observed at 300 degrees C, but at 400 degrees C decreased and at 500 degrees C or above could not be observed. Fly ash derived from burning 1 g of rice straw at 600 degrees C showed about 14 times and 2.5 times higher mutagenicity than main stream smoke condensates from the burning of 1 g of cigarette in TA100 + S9 and TA98 + S9 test systems respectively. PMID- 1747542 TI - [A study of victims of methylmercury poisoning outbreaks by age and sex in Minamata, Niigata and Iraqi outbreaks]. AB - To investigate features of the incidence of methylmercury poisoning cases presumably caused by intake of polluted foods in Japan and Iraq, several populations exposed to polluted foods were analyzed by geography and/or occupation. Ratios of confirmed cases to the corresponding number by age and sex in the defined exposed population were calculated. The distribution of the ratios showed a unimodal age distribution for both males and females in the Japanese Minamata and Niigata population. On the contrary, in the Iraqi population, ratios distributed equally by age and sex groups, having no peaks. This difference between the two countries is probably due to the difference of ingestion by age and sex in fish and wheat, which was the primary source of methylmercury exposure. PMID- 1747543 TI - [Descriptive epidemiology of 30 intractable disease patients receiving financial aid for treatment]. PMID- 1747544 TI - [Epidemiology and civil trials]. AB - The role epidemiology in courts has become increasingly important both in the United States and in Japan, especially in the field of product liability. In the United States, attributable risk percent (AR%) is used in civil trials as a measure to judge whether alleged factors caused health disturbances of plaintiffs. Most epidemiologists believe that an AR% of more than 50%, ie, relative risk more than 2, supports causality of alleged factors, because "preponderance of evidence" is regarded as a fundamental legal rule in the United States. In Japan, judges in courts require a more strict standard for proof of facts, which means that a much higher AR% may be needed to convince judges. The role of epidemiologists in courts may be to show a plausible range of AR%, based on design, execution, and analysis of quoted epidemiologic studies. Standards for accepting plaintiffs' allegation should be discussed in the legal framework of Japan. PMID- 1747545 TI - [A study of family support, health state and medical care among functionally dependent elderly in Shanghai, China]. AB - The effect of family caregiver's attitudes to elderly on health conditions of functionally dependent elderly, relationships between family support and perceived burden among family caregivers, and factors related to family support were analyzed. Support in this study was defined as help directed at helping functionally dependent elderly achieve independence or self-care. In 1989, a survey was conducted of family caregivers in Shanghai. Functionally dependent elderly were collected by screening of people aged 65 years old and over, and family caregivers who were able to provide support as defined above were included as subjects (n = 468). The following results were obtained: 1. Caregivers with positive attitudes for support had a higher proportion having the ability to obtain physician care compared to those with low family support. The proportion of persons with bedfast condition, cognitive impairment, and abnormal behaviors did not appear to have a relationships to level of family support. 2. There was only a weak relation between family support and perceived burden scale of caregivers. 3. Among all factors, the strongest relationship to family support was with educational background. The health of caregivers and the family relationship between caregivers and functionally dependent elderly were also related to level of family support. PMID- 1747546 TI - [Relationship between senile dementia and findings of an initial health examination--a 20 year retrospective cohort study of Kamo Village (1965 to 1985)]. AB - The correlation between incidence of senile dementia and variables determined in baseline health examinations was analyzed in a retrospective cohort study. The study cohort was assembled in 1965 and followed up to 1985. A survey of dementia was performed on those alive in 1985, and on the decreased through their families who were queried about his or her condition just before death. The survey was conducted by public health nurses and assistants. The results obtained were as follows: 1. There was a slightly higher incidence in women and incidence for both sexes demonstrated an increase with age. 2. Analysis by cause of death showed increased death by cerebrovascular diseases for both men and women, and by cardiovascular disease for women, but decreased death from cancer. 3. Correlations of senile dementia with high blood pressure and albuminuria findings at the initial examination were seen. In addition, results of fundus oculi examination in men, and electrocardiography in women were also regarded as risk factors for the occurrence of senile dementia. 4. Comparative analysis showed higher incidence among farmers rather than fishermen, and in drinkers rather than nondrinkers, while no relation was found to smoking habits. PMID- 1747547 TI - [Prediction of 24-hour urinary creatinine excretion from age, body weight and height of an individual and its application]. AB - Equations to predict 24-hour urinary creatinine excretion (UcrV) from age, body weight (W) and body height (H) were developed based on the data for UcrV determined by collecting 24-hour urine for 3-5 days in 256 male and 231 female clinically healthy subjects, aged from 20 to 84 years. By regression analysis a regression equation was developed. Multiple regression analysis revealed that age, W and H contributed most to the measured value of UcrV. The regression equations to predict UcrV from age, W and H were as follows: Predicted value of UcrV (PRCr) = -12.63 x Age + 15.12 x W + 7.39 x H - 79.90 (male: mg/day) PRCr = 4.72 x Age + 8.58 x W + 5.09 x H - 74.50 (female: mg/day) The multiple correlation coefficients were 0.87 for males and 0.73 for females, respectively. The difference between PRCr and measured UcrV (residual) was +0.81 +/- 154 (SD) mg/day on the average. An analysis of residuals by means of plotting of standardized residuals and predicted standardized dependent variables showed no remarkable deviations in both sexes, suggesting that these equations are applicable to the prediction of UcrV. These equations were applied to 38 Japanese men and women who were asked to collect 24-hour urine for 14 days on average, and also to 47 foreigners (American, Nepalese and Italian). The average residual in the former was +27 +/- 87 mg/day and that in the latter -3 +/- 85 mg/day, suggesting that these equations can be applied not only to the Japanese but also to the foreigners as a useful index in predicting 24-hour urinary creatinine excretion. PMID- 1747548 TI - [A report of the state of health in Zimbabwe]. AB - The health state in Zimbabwe is reported in terms of currently significant diseases, health statistics and hygiene and health care system in conjunction with the author's experiences as a visiting doctor in the country between June and September in 1989. Since independence in 1980 the government has transformed the colonial and racial health system and attempted to redistribute health care resources to the rural population. Similar to many countries in Central and East Africa, the accumulative number of AIDS cases in Zimbabwe is increasing rapidly despite the vigorous governmental campaigns launched in the early stage. The incidence of tuberculosis has also been rising since 1986 apparently in association with HIV spread in the country. On the other hand Zimbabwe is unique among the countries in Africa because rural clinics and preventive medicine such as immunization, basic sanitation and health education have been well-established throughout the country. As a result various communicable diseases common to the tropics and subtropics have been successfully controlled. The country now needs to improve quality and quantity of hospital medicine. While hospital facilities are available, the number of doctors, particularly in the district, is far below demand. Zimbabwe is one of the few countries in Africa where doctors trained in Japan could work efficiently and therefore it is suggested that it be considered as a country amenable to international medical cooperation. PMID- 1747549 TI - [Nurse's leadership to the primary care-giver in community setting]. PMID- 1747550 TI - [A manual for community mental health activities for a public health center in Japan]. AB - A system for treatment of persons with chronic mental disease such as schizophrenics in the present structure of the Japanese public Health Center is proposed. Presently, while cases are handled by responsible staff members, incorporation into the health center system with full utilization of its personnel and resources is seldom accomplished. There is a necessity for a systems approach in order to organize essential programs that would provide care for the mentally diseased. Health centers would have three main roles in this system: as a coordinator of mental health resources in the community, as a specialized agency for case management, and responsibility for public relations in its service area. For proper administration of its system, health centers should follow a team concept. The team would consist of a director of health centers, physicians, part-time psychiatrists, public health nurses, psychiatric social workers and clerical staff. At case conferences discussion of whether a prospective case should be registered, assessment of the needs, and development of management plans for all of the registered cases would be conducted. The files and documents of each case would be deleted or re-registered 5 years after initial registration. Cases would have a case-manager to coordinate public health care, including home visits, family care, psycho-educational consultation and crisis intervention. Health centers would be responsible for bringing together available social resources such as sheltered workshops and transient residential programs. The goal of health centers' mental health activities would be to facilitate the normalization of the mentally diseased within the community. PMID- 1747551 TI - [Incidence of and circumstances related to falls among the elderly in a Japanese community]. AB - In order to determine incidence of and the circumstances related to falls among the elderly in a community in Japan, general health surveys were carried out in 1988 and in 1989. Subjects for the first survey were 685 elderly residents (276 men, 409 women) aged 65 years and over, living in a rural village of Akita Prefecture. Subjects who were confined to bed almost all day were excluded from analysis. Subjects were interviewed regarding falls at both surveys. Results obtained were as follows; 1) Incidence of falls were 19.2% for men, and 20.3% for women at the first survey. There was no significant difference in incidence between sexes. 2) Age had no significant effect on incidence in either sex. 3) The incidence at the follow-up survey was significantly higher among those who had reported falls at the first survey than in those who had not (relative risk; men; 2.71, women 2.40, p less than 0.05). 4) Most falls occurred during the daytime in either sex, with approximately 90% of falls for men and 60% of falls for women occurring outdoors. The cause of falls was mainly extrinsic. Compared to men, falls of women had a greater tendency to lead to major injury. PMID- 1747552 TI - [A study of falls experienced by the aged among users of preventive health examination services]. AB - In order to determine what factors are related to falls and the effect on the aged, a study was conducted on subjects aged 60 years and over who had undergone preventive health examinations in the western region of Shizuoka Prefecture. Subjects (n = 305) had an average age of 64.4 +/- 3.8 years, and all were interviewed regardless of their history of falls. For the 66 cases who had experienced falls, further questions prepared in advance, were included. The following results were obtained: 1) There were 66 subjects (21.6% of the subjects) who had experienced falls with some experienced multiple falls for a total count of 91 falls. 2) The frequency of falls of female subjects was significantly higher than that of males. Further, with respect to the type of injuries suffered, in the case of many of the female subjects, these took the form of contusions. 3) The majority of subjects who experienced falls were engaged in farming and most of the falls were work-related. 4) Results of this study showed that, while not statistically significant, cerebrovascular diseases are closely connected to falls and increases the falls coefficient among the aged. PMID- 1747553 TI - [A community-based education program for serum cholesterol reduction in urban hypercholesterolemic persons--comparison of intensive and usual education groups]. AB - A community-based education program was conducted for persons found to be hypercholesterolemic by screening during cardiovascular surveys, in an urban population, to evaluate the feasibility and effect of the program in primary prevention of coronary heart disease. The subjects were men and women aged 40-64 living in the suburbs of Osaka whose serum total cholesterol was between 240 and 299 mg/dl in both the 1988 and the 1989 surveys. Persons with hypothyroidism, those taking medication for hypercholesterolemia or hypertension, and with a history of stroke and coronary heart disease were excluded. Of the 111 persons who were eligible, 104 persons were recruited for the program on March, 1989. The 104 persons were randomly assigned to either an intensive education group (n = 51) or a usual education group (n = 53). For the intensive education group, seven education classes were held from April to November, 1989. Lectures, practice sessions, interviews, and spot cholesterol measurements were conducted in a local community center. The usual education group received a letter with results from the 1989 survey and dietary instruction in April 1989 and an education class in September 1989. Mean serum cholesterol in the intensive education group showed a 10.0 mg/dl greater reduction in September 1989 and a 9.0 mg/dl greater reduction in March 1990 than in the usual education group (p less than 0.05) while mean HDL cholesterol did not change in either groups. The intensive education group reported a larger decrease in the dietary frequency of chicken egg, poultry skin and small fishes, foods which are rich in saturated fat and cholesterol. The frequency of fatty meat, butter and fish eggs was low in both groups and did not differ between the two groups after the one-year program. These results indicate that a population-based education program is feasible and effective in reducing serum total cholesterol of hypercholesterolemic persons. PMID- 1747554 TI - [Asbestos concentration and fiber size in lungs of the urban residents]. AB - Asbestos fiber concentrations and fiber size distribution in lung tissues of 53 urban residents (males: 34, female: 19) were analyzed by low temperature ashing analytical transmission electronmicroscopy. The following findings were obtained. 1. Pulmonary asbestos fibers were found in 51 out of 53 patients. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite and tremolite. 2. Thirty-six of 53 patients had no history of occupational asbestos exposure, and their geometric mean concentration of asbestos fibers was 1.67 x 10(6) fibers/g dry lung. Most of these asbestos fibers are probably attributable to general environmental contamination. Thirteen patients who had a history of occupational asbestos exposure showed a geometric mean of their pulmonary asbestos concentrations (5.82 x 10(6) fibers/g dry lung) which was significantly higher than that of patients without occupational asbestos exposure (p less than 0.01). 3. The geometric mean concentration of asbestos fiber in males (2.70 x 10(6)) was higher than in females (1.59 x 10(6)), probably due to a difference in the occupational asbestos exposure between males and females. 4. Regardless of the patient's sex, the geometric mean concentration of asbestos fibers in patients without a history of smoking (male: 4.91 x 10(6), female: 1.78 x 10(6)) was higher than that in patients with a smoking history (male: 2.76 x 10(6), female: 1.37 x 10(6)). The difference, however, was not statistically significant, and no correlation was seen between the concentration of asbestos fibers and smoking history. 5. Although most asbestos fiber utilized in Japan is chrysotile, the geometric mean concentration of chrysotile (0.87 x 10(6)) was almost identical to that of amphibole asbestos fiber (0.90 x 10(6)). 6. Of the asbestos fibers observed, 95% of chrysotile and 85% of amphibole asbestos were less than 5 microns in length and 93% of the total asbestos fibers were too small to be visible by light microscopy. PMID- 1747555 TI - [Indications and value of endosonography of the upper gastrointestinal tract]. AB - Endoscopic ultrasound (EUS) has been used in the diagnosis and staging of gastroenterologic tumors for about ten years. High accuracy rates of EUS in staging of esophageal, gastric and pancreatic carcinoma (T-stage: 80-95%, N stage: 75-85%) have been reported. EUS is therefore a valuable diagnostic tool fur assessment of prognosis as well as for planning of therapy of these tumors. Its value in benign gastroenterologic disease is unclear. EUS seems to be much less reliable in the differentiation between benign and malignant changes (e.g. esophageal stenoses, gastric ulcers, pancreatic mass lesions). PMID- 1747556 TI - [Endosonography of the rectum]. AB - Endorectal ultrasound is proving to be a very accurate method for the preoperative staging of cancer. The tumor penetration depth is assessed with an accuracy of more than 90% for all T stages. The preoperative endosonographic evaluation of lymph nodes is superior to other imaging modalities, being more than 80% accurate in comparison to CT and lymphoscintigraphy. It is relatively easy to perform and inexpensive compared with other imaging modalities. It has proved its influence on decision making, selection for local therapy, planning of radiotherapy and reoperation of early tumor recurrencies. PMID- 1747557 TI - [Improvements in 3-D ultrasonic imaging]. AB - The problem of gaining a coordinated sequence of section cuts by ultrasound is solved by rotating the plane section around a vertical and a horizontal axle. There are two possibilities in presenting the 3D image of the examined organ: ring structure image or transparent image. Precondition in the ring structure image is time consuming and defective since it has to be done by hand using a cursor. These pitfalls can be avoided when using a method without contouring by showing the 3D image transparently. Each section cut has to be calculated transparently. Both methods are presented in this paper and compared as to their applicability in medicine. The problem of the transparent 3D presentation lies in the fact that it cannot be well presented on printed paper, as is done her. The moving picture on the computer screen gives an optimal 3D image. This new method seem to be useful in tumor diagnostic and diagnostic of malformations in early pregnancies. PMID- 1747558 TI - [Use of the 3D procedure in nuclear magnetic resonance tomography in ENT diagnostics]. AB - The use of 3D-gradient-echo sequences improved the diagnosis of malignant tumors of the skull base, the nasopharynx, the nasal cavities, the paranasal sinuses and the upper parts of the parapharyngeal space with relation to the skull base. Therefore the tumor extent and infiltration may be better appreciated than in conventional 2D-spin-echo or gradient echo sequences. Using this method, the examinations of 22 patients with carcinomas could be compared. Precise tumor delineation was achieved in six of these patients when compared with surgical and histological findings. The 3D sequences most frequently used were FLASH 40 degrees with TR of 40 ms and the shortest TE (5 to 6 ms). 3D turbo-FLASH (MPRage) with Gad-DTPA was applied in order to shorten the acquisition time by half and especially to reduce motion artefacts. PMID- 1747559 TI - [Para-pleural lung lesions: diagnostic value of sonography versus computerized tomography]. AB - 45 patients with pleural and/or peripheral lung lesions detected by chest radiography were examined by chest ultrasound. A chest CT-scan was obtained as a reference method afterwards. In 43 pleural or peripheral lung lesions we found corresponding results comparing size, invasivity and nature comparing the two diagnostic methods. In 35 of 41 cases an ultrasound (US)-guided needle biopsy confirmed the preliminary diagnosis suspected after sonography of the chest. Six needle biopsies allowed no definite diagnosis. Two patients developed a pneumothorax that required drainage after US-guided needle biopsy. CONCLUSION: Real-time sonography of the chest and chest CT-scans are complementary methods examining pleural and peripheral lung lesions, corresponding results are demonstrated in respect of location, size, invasivity and nature of the lesions. PMID- 1747560 TI - [Tumors of the oropharynx, hypopharynx and larynx--diagnosis with magnetic resonance imaging]. AB - 312 patients with neoplasms of the oropharynx, hypopharynx and larynx--301 of these suffered from malignancies--were examined with use of magnetic resonance imaging (MRI) and--in most cases--with computed tomography (CT) for comparison. MRI yielded better results than CT in the case of oropharyngeal tumors. With regard to hypopharyngeal tumors, however, slight discrepancies in the diagnostic capacities of both methods were observed. MRI afforded a clearer tumor definition through sagittal and coronal slice orientations. In the case of laryngeal neoplasms in the glottic region, CT is currently superior to MRI. This could change in the future as a result of improvement in signal behavior of the 2D gradient echo (2D GE) sequences and of the use of phonation studies (Turbo FLASH). MRI, on the other hand, is superior to CT in the definition of sub-, supra- and panglottic tumors. PMID- 1747561 TI - Dysphagia of the treated laryngeal cancer--detection of functional and morphological changes by cineradiography. AB - After treatment of laryngeal cancer 35 patients with dysphagia have been examined by high speed cineradiography. When compared to normal swallowing patterns, the following abnormalities were observed: Excursion of the posterior pharyngeal wall during swallowing is twice as intensive as normal. The function of the base of the tongue becomes more important for pharyngeal emptying--a fact that surgeons should take into consideration when planning laryngeal resection. Timing of pharyngeal constriction and function of the upper esophageal sphincter are definitively altered. In view of these changes we think that cineradiography can help to find better methods for functional surgery of the pharynx and the adjacent structures. PMID- 1747562 TI - Ectopic pregnancy in an uncommon location revealed by ultrasound. AB - We report the case of extrauterine intraovarian pregnancy of a young woman. The patient was preoperatively examined by ultrasound which revealed extrauterine pregnancy of the fourth lunar month. Histologically, intraovarian gravidity of four months was proven. PMID- 1747564 TI - [8th International Symposium. Endoscopic ultrasonography, Munich 15 June 1991]. PMID- 1747563 TI - CT appearance of shearing injuries of the brain. AB - Shearing injuries, also called diffuse axonal injuries, are a special kind of severe head trauma, usually caused by a motor vehicle accident, in which disruption of white matter axons takes place. Twelve cases of shearing injuries were diagnosed by computed tomography (CT). The typical CT findings were small hemorrhagic lesions in the cerebral white matter, most often in cerebral hemispheres and internal capsules. In most patients, hemorrhagic foci were multiple. Single lesions were found in only two patients. Features of brain edema were found in eight of ten early studies, and subarachnoidal hemorrhage only in three. Two patients also had subdural hematomas. CT appearance of the shearing injuries is characteristic, especially in connection with clinical data indicating a history of head trauma and severe state of the patient. PMID- 1747565 TI - A serum substitute promotes osteoblast-like phenotypic expression in cultured cells from chick calvariae. AB - The effects of medium supplements were tested on embryonic chick calvarial cells in culture. Isolates were divided among four treatment groups: Nu-Serum, chicken serum, fetal bovine serum, or calf serum. Expression of the osteoblastic phenotype was assessed by cell morphology, DNA content, [3H]thymidine incorporation, lactate production, cellular and medium alkaline phosphatase activities, and collagen synthesis. Cells grown in Nu-Serum demonstrated increased alkaline phosphatase activity and a six-fold higher rate of collagen synthesis compared to chicken serum. These cells displayed a polygonal profile, abundant rough endoplasmic reticulum, Golgi apparati, and elaborated an extensive matrix of banded collagen which was well mineralized by day 10 of culture. Although highly mitogenic, chicken serum promoted a more fibroblastoid morphology. Compared to the sera tested, Nu-Serum preferentially promoted the osteoblast-like phenotype in chick calvarial cells in culture. PMID- 1747566 TI - Estrogens reduce bone loss in the ovariectomized, lactating rat model. AB - Estrogen treatment of ovariectomized, lactating rats improved retention of bone mineral mass by 15-25% compared to ovariectomized, lactating rats receiving vehicle only. On the second day postpartum all lactating rats were ovariectomized and were placed along with age-matched non-mated controls on a whole-wheat flour based diet with 0.1% calcium and 0.4% phosphorus. On day 6 postpartum estrogen treatment was begun with either implantation of a slow-release 17 beta-estradiol pellet or with the first of daily subcutaneous injections in sesame oil (vehicle). Increasing doses of estrogen resulted in decreased food consumption and decreased litter weight gain, both well-known effects of estrogens. Ovariectomized, lactating rats implanted with a slow-release pellet containing 0.35 mg 17 beta-estradiol had mean serum estradiol levels of 113.5 pg/ml. At the end of 21 days of lactation, femurs of dams with placebo pellets showed loss of 54% of bone ash weight compared with the non-mated controls versus only 42% loss by rats receiving estradiol treatment. Rats were also injected with estradiol benzoate in a sesame oil vehicle at 3 dose levels of 1.6, 5, or 16 micrograms/day. Only the 5 and 16 micrograms/day doses significantly improved retention of bone mineral mass during lactation (+17% and +18%, respectively, vs vehicle-injected, lactating rats). Estrone administered by subcutaneous injection also improved retention of bone during lactation; however, injection of 50 micrograms/day of estrone was required to produce an equivalent bone retention compared to 5 micrograms/day of estradiol. Thus, treatment of ovariectomized, lactating rats with estrogens results in a significant reduction of the loss of bone mineral mass associated with lactation. PMID- 1747567 TI - Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats. AB - The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: 1) increased bone width and mineral density; 2) increased total tissue and total bone areas; 3) decreased marrow area; 4) increased periosteal and corticoendosteal lamellar bone formation; 5) activated corticoendosteal lamellar and woven trabecular bone formation and 6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2. PMID- 1747569 TI - Selected bibliography. PMID- 1747568 TI - The prevention of corticosteroid-induced osteoporosis with nandrolone decanoate. AB - The effects of nandrolone decanoate (ND; 50 mg IM every three weeks) on calcium metabolism and forearm bone density were studied in a randomized trial in 35 women receiving long-term therapy with corticosteroids (CST) for rheumatic disease. The 17 patients who served as controls were on CST therapy for less years and their bone density was higher. Thus a second control group, pair matched with the active treatment group for age, duration of CST therapy and bone density, was selected retrospectively. At the end of the 18 months' treatment course with ND, forearm bone density was increased by 5.1% (P less than 0.01) but fell by 11.3% (P less than 0.01) and 6.7% respectively in the first and second control group. The patients on ND differed significantly from both control groups in the changes at 6, 12 and 18 months (P less than 0.01). Urinary excretion of hydroxyproline fell significantly in patients receiving ND, whereas the biochemical indices of bone formation did not change (alkaline phosphatase) or increased (osteocalcin; P less than 0.01). In conclusion, nandrolone decanoate therapy may be used in the prevention of CST-induced osteoporosis. It also seems to exert mild inhibition of bone resorption without affecting or even stimulating bone formation. PMID- 1747570 TI - How will the single European market affect health care? PMID- 1747571 TI - Rugby injuries. PMID- 1747572 TI - Neonatal vitamin K. PMID- 1747573 TI - Salt substitutes and potassium intake. PMID- 1747574 TI - More radiotherapists, please. PMID- 1747575 TI - General practitioners' pay. PMID- 1747576 TI - Criminal charges over HIV in French blood transfusions. PMID- 1747577 TI - beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination. AB - OBJECTIVE: To determine the effects of the beta 1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication. DESIGN: Randomised controlled double blind four way crossover trial. SETTING: Royal Hallamshire Hospital, Sheffield. SUBJECTS: 49 patients (40 men) aged 39-70 with chronic stable intermittent claudication. INTERVENTIONS: Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments. MAIN OUTCOME MEASURES: Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales. RESULTS: Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to -13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p less than 0.003)) and skin temperature of the more affected foot (-1.1 degrees C; 0 to -2.2 degrees C (p = 0.05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes. CONCLUSIONS: There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to beta blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication. PMID- 1747578 TI - Haemorrhagic disease of the newborn in the British Isles: two year prospective study. AB - OBJECTIVE: To determine the incidence of haemorrhagic disease of the newborn in the British Isles, study risk factors, and examine the effect of vitamin K prophylaxis. DESIGN: Prospective survey of all possible cases of haemorrhagic disease of the newborn as reported by consultant paediatricians using the monthly notification cards of the British Paediatric Surveillance Unit and a follow up questionnaire for each case to validate the diagnosis and accrue further data. SETTING: Britain (England, Scotland, and Wales) and Ireland (Northern Ireland and the Irish Republic) during December 1987 to March 1990. PATIENTS: 27 infants classified as having confirmed (n = 25) or probable (n = 2) haemorrhagic disease of the newborn. RESULTS: 24 of the 27 infants were solely breast fed. 10 suffered intracranial haemorrhage; two of these died and there was clinical concern about the remainder. 20 infants had received no vitamin K prophylaxis, and seven had received oral prophylaxis. Relative risk ratios for these groups compared with babies who had received intramuscular vitamin K were 81:1 and 13:1 respectively. Six infants had hepatitis (alpha 1 antitrypsin deficiency in four), unsuspected until presentation with haemorrhagic disease of the newborn, of whom four had received oral prophylaxis. One other baby had prolonged jaundice. One mother had taken phenytoin during pregnancy. CONCLUSIONS: All newborn infants should receive vitamin K prophylaxis. Intramuscular vitamin K is more effective than oral prophylactic regimens currently used in the British Isles. PMID- 1747579 TI - Vitamin K prophylaxis against haemorrhagic disease of the newborn in the United Kingdom. PMID- 1747580 TI - Potassium concentrations in irradiated blood. PMID- 1747581 TI - Children seen frequently out of hours in one general practice. AB - OBJECTIVE: To identify reasons why some children receive more out of hours visits than most. DESIGN: A one year prospective study to identify the study group. This was followed by a case-control study involving a record search and personal interviews. SETTING: One three doctor urban general practice in West Lothian with 4812 patients. SUBJECTS: 40 children aged under 10 years identified as high users of the out of hours service (more than two visits a year) and 40 age and sex matched controls. MAIN OUTCOME MEASURES: Numbers of visits; social factors such as lone motherhood, low educational attainment; score for management response to clinical vignette. RESULTS: 147/756 (19%) out of hours visits in the study year were to children aged under 10 years; 109 (74%) to 41 children (6%). Problems seen were mainly minor, and little active management was required. Family and social factors which were significantly more common for the cases than for the controls included a lone mother (15 v 4), low educational attainment by the mother (25 v 14), receipt of income support (22 v 7), and non-ownership of the home (45 v 22) or a car (19 v 9). Mothers of the cases were more likely to choose to contact a doctor when presented with vignettes describing common childhood illnesses (median score for 16 vignettes 16.5 for cases v 14.5 for controls, Wilcoxon signed rank test, p = 0.01). CONCLUSIONS: Children seen more frequently than expected out of hours came from more socially disadvantaged families and their mothers were more likely to seek medical advice about minor childhood illness. Maternal education, to promote confidence in managing minor illness, may reduce their use of the out of hours service. PMID- 1747582 TI - The Health of the Nation: responses. Strategy full of good intentions. PMID- 1747583 TI - What the government should do. PMID- 1747584 TI - Using the potential of all staff. PMID- 1747585 TI - Importance of a healthy environment. PMID- 1747586 TI - ABC of vascular diseases. Treating aortic aneurysms. PMID- 1747587 TI - General practitioners' awareness of COSHH regulations. PMID- 1747588 TI - Health of the nation. PMID- 1747589 TI - Seafarers and HIV infection. PMID- 1747590 TI - Monkey business over AIDS vaccine. PMID- 1747591 TI - Routine testing for HIV infection at fertility clinics. PMID- 1747592 TI - Counselling patients before an HIV test. PMID- 1747593 TI - Hypertension and non-insulin dependent diabetes. PMID- 1747594 TI - Inner city psychiatry. PMID- 1747595 TI - Management of convulsions with fever. PMID- 1747596 TI - Incentives to fundholding. PMID- 1747597 TI - Preventing coronary heart disease in primary care. PMID- 1747598 TI - Informed consent. PMID- 1747599 TI - We may never understand each other. PMID- 1747600 TI - Junior doctors' hours. PMID- 1747601 TI - Outpatient physicians. PMID- 1747602 TI - Burning down their houses. PMID- 1747603 TI - Avoiding autocannibalism. PMID- 1747604 TI - Patient's charter. PMID- 1747605 TI - Surgical pathology and general practice. PMID- 1747606 TI - Preventing AIDS now. PMID- 1747607 TI - AIDS surveillance in Africa. PMID- 1747608 TI - Parent support groups. PMID- 1747609 TI - Auditing AIDS spending. PMID- 1747610 TI - French will compensate for infected blood. PMID- 1747611 TI - Relation of coronary heart disease and apolipoprotein E phenotype in patients with non-insulin dependent diabetes. AB - OBJECTIVES: To examine the relation between coronary heart disease and the apolipoprotein E phenotypes in patients with non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study. SETTING: District around Kuopio University Central Hospital, East Finland. SUBJECTS: 138 men with non-insulin dependent diabetes and 64 men without diabetes as controls. MAIN OUTCOME MEASURE: Apolipoprotein E phenotype, electrocardiographic abnormalities, other signs of coronary heart disease. RESULTS: The prevalences of definite myocardial infarction and ischaemic electrocardiographic changes were highest in the diabetic men with the phenotypes E4/4 or E4/3 (25% (95% confidence interval 18% to 32%) and 50% (42% to 58%) respectively), although the difference between the phenotype groups was not significant. The prevalence of angina pectoris was 69% (61% to 77%) in men with the phenotypes E4/4 or E4/3 (p = 0.005 compared with other phenotypes), 41% (33% to 49%) in men with phenotype E3/3, and 47% (39% to 55%) in those with phenotypes E2/2 or E2/3. Similarly, the simultaneous presence of angina pectoris and ischaemic electrocardiographic changes was highest in the diabetic men with the phenotypes E4/4 or E4/3 (42% v 22% in those with E3/3 and 29% in those with E2/2, E2/3; p = 0.038). Overall, the prevalence of any evidence of coronary heart disease among the diabetic subjects with the phenotypes E4/4 or E4/3 was 81% (p = 0.011 compared with other phenotypes), 58% in those with phenotype E3/3, and 53% in those with phenotypes E2/2 or E3/3. CONCLUSION: Apolipoprotein E phenotypes E4/4 and E4/3 modulate the risk of coronary heart disease in men with non-insulin dependent diabetes. PMID- 1747612 TI - Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy. AB - OBJECTIVE: To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN: Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING: Gastroenterology department of teaching hospital. PATIENTS: 96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES: Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS: 28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION: Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient. PMID- 1747613 TI - Effectiveness of routine ultrasonography in detecting fetal structural abnormalities in a low risk population. AB - OBJECTIVE: To review the efficacy of routine prenatal ultrasonography for detecting fetal structural abnormalities. DESIGN: Retrospective study of the ultrasonographic findings and outcome of all pregnancies in women scanned in 1988 9. SETTING: Maternity ultrasonography department of a district general hospital. SUBJECTS: 8785 fetuses. MAIN OUTCOME MEASURES: Correlation of prenatal ultrasonographic findings with outcome in the neonate. RESULTS: 8733 babies were born during 1988-9, and 52 pregnancies were terminated after a fetal malformation was identified. 8432 (95%) of the fetuses were examined by ultrasonography in the second trimester. 130 fetuses (1.5%) were found to have an abnormality at birth or after termination of pregnancy, 125 of which had been examined in the second trimester. In 93 cases the abnormality was detected before 24 weeks (sensitivity 74.4%, 95% confidence interval to 66.7% to 82.1%. Two false positive diagnoses occurred, in both cases the pregnancies were not terminated and apparently normal infants were born. This gives a specificity of 99.98% (99.9% to 99.99%). The positive predictive value of ultrasonography in the second trimester was 97.9% (92.6% to 99.7%). Of the 125 abnormalities, 87 were lethal or severely disabling; 72 of the 87 were detected by the routine screening programme (sensitivity 82.8%, 73.2% to 90.0%). CONCLUSION: Routine fetal examination by ultrasonography in a low risk population detects many fetal structural abnormalities but can present several dilemmas in counselling. PMID- 1747614 TI - Can morbidity associated with untreated asthma in primary school children be reduced?: a controlled intervention study. AB - OBJECTIVE: To determine whether an intervention programme based on existing school and community resources can reduce school absence and improve participation in games lessons and sport in children with unrecognised or undertreated asthma. DESIGN: Parallel group controlled intervention study. SETTING: 102 primary schools in Nottingham: 49 were randomised to receive the intervention and 53 to be control schools. SUBJECTS: All children aged 5 to 10 years with parent reported absence from school because of wheezing in the previous year and taking no treatment or beta agonists only. INTERVENTIONS: Children with asthma were referred to their general practitioner for assessment of symptoms and treatment. Teachers were given education on asthma by the school nurse in 44 of the 49 intervention schools. MAIN OUTCOME MEASURES: Changes in school absence and missed games and swimming lessons because of wheezing, and schools' policy towards management of asthma in school. RESULTS: Of 17,432 children screened, 451 met the entry criteria--228 in intervention schools and 223 in control schools. 152 (67%) children in intervention schools visited their general practitioner, of whom 39 (26%) were given a new diagnosis of asthma and 58 (38%) had treatment for asthma increased or changed. Over the next academic year mean (SE) parent reported school absence due to wheezing fell significantly, but to a similar extent, in both intervention and control schools (0.82 (0.11) and 1.09 (0.21) weeks respectively). There was little change in school recorded absence or participation in games lessons and swimming lessons in either group. At the end of the study intervention schools were more likely to have improved aspects of management of asthma in school. CONCLUSION: The intervention resulted in a majority of children being assessed by their general practitioner and improved teachers' understanding and management of asthma, but it did not result in any appreciable reduction in morbidity. PMID- 1747615 TI - Surveillance of antibody to rubella virus in Grampian: closing the immunity gap. AB - OBJECTIVES: To identify causes for the continuing deficit of rubella immunity in women of childbearing age with a view to further reducing the risk of the congenital rubella syndrome. DESIGN: A questionnaire was sent to the general practitioner and a laboratory follow up study conducted in a one year cohort of women found on screening to have inadequate protection against rubella. SETTING: Virus laboratory of the department of medical microbiology, Aberdeen, serving the health board areas of Grampian, Orkney, and Shetland. PATIENTS: 239 women whose concentration of antibodies to rubella virus was either absent or below standard (15,000 IU/l) and whose general practitioner could be contacted to supply a history of infection, immunisation, pregnancy, and antibody testing. MAIN OUTCOME MEASURES: Whether rubella vaccination was given and whether those vaccinated were tested for seroconversion. RESULTS: Only 122 (55%) of the women for whom information was available received the recommended vaccine; only 74 (61%) of these were tested for seroconversion. Oversight was the reason given for not vaccinating 64 (65%) of the women who remained at risk. Women who were pregnant when tested were significantly less likely to receive vaccine (odds ratio 3.36) than women who were not pregnant, and even if vaccinated were less likely to have a follow up antibody test (odds ratio 1.94). CONCLUSION: Once women are identified as being unprotected against rubella they are often overlooked and not vaccinated. Prompting mechanisms aimed at general practitioners, such as the one recently set up in Grampian, should reduce the immunity gap and help to eradicate rubella in pregnancy. PMID- 1747616 TI - Performance of skin biopsies by general practitioners. AB - OBJECTIVE: To evaluate and appraise skin biopsies performed by general practitioners and compare their performance with that of hospital doctors. DESIGN: Retrospective analysis of histology records. SETTING: University hospital. SUBJECTS: Records of 292 skin biopsy specimens obtained by general practitioners and 324 specimens obtained by general and plastic surgeons. MAIN OUTCOME MEASURES: Clinical and pathological diagnoses and completeness of excision. RESULTS: The number of specimens received from hospital surgeons and general practitioners increased over the study period; the proportion of specimens from general practitioners rose from 17/1268 (1.3%) in 1984 to 201/2387 (8.7%) in 1990. The range of diagnoses was similar among hospital and general practitioner cases, although malignancy was commoner in hospital cases (63/324 (19%) v 14/292 (5%) in general practitioner cases; chi 2 = 28, p less than 0.00001). Completeness of excision was less common among general practitioners than hospital surgeons (150/233 (3/15 malignant) v 195/232 (57/63); chi 2 = 22, p less than 0.00001). CONCLUSIONS: The increase in minor surgery has implications for the staffing and finance of histopathology departments. General practitioners must be given proper training in performing skin biopsies, and all specimens should be sent for examination. PMID- 1747617 TI - Skin biopsy in general practice. PMID- 1747618 TI - Effect of general practitioner contract on referral of specimens for histological examination. PMID- 1747619 TI - Continuity of care: influence of general practitioners' knowledge about their patients on use of resources in consultations. AB - OBJECTIVE: To examine the relation between general practitioners' knowledge about their patients and the use of resources in consultations. DESIGN: A cross sectional evaluation of consultations. SETTING AND SUBJECTS: A representative sample of 133 Norwegian general practitioners were each asked to record 30 consecutive consultations. 131 did so, and of 3990 possible registrations, 3918 (98%) were evaluated. MAIN OUTCOME MEASURES: The influence, as assessed by the doctor, of accumulated knowledge on the use of laboratory tests, expectant management, prescriptions, sickness certification, referrals, and time spent in the consultation. RESULTS: Accumulated knowledge was a substantial factor in saving time, especially in consultations with children, the elderly, patients with psychosocial problems, and those with chronic diseases. It also influenced the overall use of laboratory tests, expectant management, sickness certification, and referrals, and to a lesser degree the use of medication. CONCLUSION: The findings imply strong but complex associations between accumulated knowledge and the use of resources in the consultation. PMID- 1747620 TI - For debate. AIDS surveillance in Africa: a reappraisal of case definitions. PMID- 1747621 TI - What use is a clinical case definition for AIDS in Africa? PMID- 1747622 TI - ABC of vascular diseases. Peripheral arteriovenous malformations. PMID- 1747623 TI - Health and the environment. Population: more than a numbers game. PMID- 1747624 TI - Health of the nation. PMID- 1747625 TI - Fluoxetine and suicide. PMID- 1747626 TI - Omeprazole. PMID- 1747627 TI - Topical anaesthesia in upper gastrointestinal endoscopy. PMID- 1747628 TI - Adenoma screening and colorectal cancer. PMID- 1747629 TI - Orthopaedic surgeons and thromboprophylaxis. PMID- 1747630 TI - Haemophilus influenzae type b invasive disease. PMID- 1747631 TI - Corticosteroids and tuberculosis. PMID- 1747632 TI - Lies, damned lies, and waiting lists. PMID- 1747633 TI - Changing patterns of work. PMID- 1747634 TI - Winter pressure on hospital beds. PMID- 1747635 TI - The RCGP approaches 40. PMID- 1747636 TI - Auditing necropsies. PMID- 1747637 TI - Reforming health care in the United States. PMID- 1747638 TI - Does triamterene cause renal calculi? PMID- 1747639 TI - Manslaughter convictions for making mistakes. PMID- 1747640 TI - Trials of HIV vaccine planned for developing countries. PMID- 1747641 TI - Group cognitive and behavioural treatment for hypochondriasis. AB - OBJECTIVE: To assess the feasibility of carrying out group cognitive and behavioural treatment for hypochondriasis in a general hospital setting. DESIGN: Assessment of patients referred for therapy. SETTING: District general hospital. PATIENTS: Six patients aged 35 to 55 (mean 43) years with a mean duration of symptoms of 12 years who fulfilled the Diagnostic and Statistical Manual for Mental Disorders (DSM III-R) criteria for hypochondriasis. MAIN OUTCOME MEASURES: Number of visits to their doctors, time spent thinking about illness, and scores on the hospital anxiety and depression scales. RESULTS: The mean number of visits to a doctor fell significantly after treatment (3 before treatment v 0.8 after treatment; p = 0.03) as did the time spent thinking about illness (57.3 v 40.6; p = 0.14). The depression and anxiety scores also fell, although the differences were not significant (depression: 9.5 before v 8.5 after; anxiety: 13 before v 12 after). CONCLUSION: It is feasible to carry out group cognitive and behavioural treatment in patients with hypochondriasis, and controlled studies are now indicated. PMID- 1747642 TI - Detention of British citizens as hostages in the Gulf--health, psychological, and family consequences. AB - OBJECTIVE: To describe the physical, psychological, and family consequences of the detention of British subjects as hostages in Kuwait or Iraq, or both, after the invasion of Kuwait on 2 August 1990 and to investigate the relation between types of trauma experienced and these reactions. DESIGN: Postal questionnaire. SUBJECTS: 381 respondents. RESULTS: Many health, social, and psychological sequelae were identified. Problems with present finance, accommodation, and work are important causes of distress. Many hostages coped well and gained self esteem. CONCLUSIONS: A minority of respondents require further support and treatment. Expatriates in risk areas should retain assets in their home country. PMID- 1747643 TI - Caffeine restriction: effect on mild hypertension. AB - OBJECTIVE: To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure. DESIGN: Four way, randomised, crossover trial of four consecutive two week dietary regimens: normal diet, caffeine free diet alone, caffeine free diet with decaffeinated instant coffee, caffeine free diet with caffeinated instant coffee (instant coffee phases conducted double blind). SETTING: Hospital hypertension clinic, Scotland. PATIENTS: 52 patients (23 men; aged 26-67 years) with untreated borderline or mild hypertension (diastolic blood pressure 90-105 mm Hg) who normally drank a minimum of three cups of coffee daily. MAIN OUTCOME MEASURES: Mean ambulatory blood pressure over 24 hours; mean morning, daytime, and night time ambulatory blood pressure; sitting clinic blood pressure at 1700; plasma caffeine concentration at 1700 on the last day of each regimen. RESULTS: Mean 24 hour ambulatory blood pressure was not different between regimens. There was no difference in blood pressure variability between regimens. During the caffeine free diet alone morning ambulatory diastolic blood pressure was higher (2.8 mm Hg) than during the caffeine free diet with caffeinated coffee. Mean sitting clinic systolic blood pressure was higher at 1700 (4.7 mm Hg) with a caffeine free diet than with the caffeine free diet with caffeinated coffee (p less than 0.05). Dietary compliance as assessed by plasma caffeine concentration was excellent. There was no significant correlation between plasma caffeine concentration and blood pressure. CONCLUSIONS: Drinking caffeinated instant coffee over a two week period does not adversely influence blood pressure in patients with borderline or mild hypertension; abstinence is of no benefit. PMID- 1747644 TI - Eradicating Helicobacter pylori and symptoms of non-ulcer dyspepsia. AB - OBJECTIVE: To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia. DESIGN: Four week prospective study. SETTING: One hospital outpatient and endoscopy department. PATIENTS: 90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic, biliary, pancreatic, or malignant disease; all had histological and microbiological evidence of infection with H pylori. 83 patients completed the treatment regimen. INTERVENTION: Colloidal bismuth subcitrate 120 mg four times a day for four weeks (27 patients); metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week (27); and bismuth subcitrate 120 mg four times a day for four weeks, metronidazole 400 mg three times a day for one week, plus amoxycillin 500 mg three times a day for the first week (29). MAIN OUTCOME MEASURES: Change in symptom scores determined with questionnaire; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens. RESULTS: Overall, H pylori was eradicated in 41 (49%) patients. Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated (from 1.56 to 0.61, p less than 0.01 v from 1.83 to 1.07, p = 0.52) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated (3.0 v 2.3, NS). Similarly the mean symptom score improved whether or not gastritis improved (2.8 v 3.1 respectively, p = 0.72). The observations were similar for treatment groups analysed individually. CONCLUSION: Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term. PMID- 1747645 TI - Relation between Glasgow coma scale and the gag reflex. PMID- 1747646 TI - Pre-eclampsia: discordance among identical twins. PMID- 1747647 TI - Safety of thrombolysis in association with cardiopulmonary resuscitation. PMID- 1747648 TI - Anal human papillomavirus infection in heterosexuals with genital warts: prevalence and relation with sexual behaviour. PMID- 1747649 TI - Communication of results of necropsies in north east Thames region. AB - OBJECTIVE: To evaluate the adequacy of reporting of results of necropsy to referring clinicians and to general practitioners. DESIGN: Questionnaire survey of referring clinicians and general practitioners of deceased patients in four districts in North East Thames region. Patients were selected by retrospective systematic sampling of 50 or more necropsy reports in each district. SETTING: One teaching hospital, one inner London district general hospital, and two outer London district general hospitals. PARTICIPANTS: 70 consultants and 146 general practitioners who were asked about 214 necropsy reports; coroners' reports were excluded. MAIN OUTCOME MEASURES: Time taken for dispatch of final reports after necropsy, consultants' recognition of the reports, general practitioners' recognition of the reports or of their findings, and consultants' recall of having discussed the findings with relatives. RESULTS: Only two hospitals dispatched final reports including histological findings (mean time to dispatch 144 days and 22 days respectively). 42 (60%) consultants and 83 (57%) general practitioners responded to the survey. The percentage of reports seen by consultants varied from 37% (n = 13) to 87% (n = 36); in all, only 47% (39/83) of general practitioners had been informed of the findings by any method. Consultants could recall having discussed findings with only 42% (47/112) of relatives. CONCLUSIONS: Communication of results of necropsies to hospital clinicians, general practitioners, and relatives is currently inadequate in these hospitals. IMPLICATIONS AND ACTION: A report of the macroscopic findings should be dispatched immediately after necropsy to clinicians and general practitioners; relatives should routinely be invited to discuss the necroscopic findings. One department has already altered its practice. PMID- 1747650 TI - Medical audit: the Spanish experience. PMID- 1747651 TI - Effectiveness and efficiency under competition: the Cochrane test. PMID- 1747652 TI - Health implications of climatic change. PMID- 1747653 TI - Booked admissions as a replacement for waiting lists in the new NHS. PMID- 1747654 TI - Edit a staff round. PMID- 1747655 TI - ABC of vascular diseases. Thrombosis and pulmonary embolism. PMID- 1747656 TI - Human insulin. PMID- 1747657 TI - Aging and rationing. PMID- 1747658 TI - Chemotherapy in advanced ovarian cancer. PMID- 1747659 TI - Developing new drugs for cancer. PMID- 1747660 TI - Sudden deafness after dental surgery. PMID- 1747661 TI - Necropsy as a monitor of clinical diagnosis performance. PMID- 1747662 TI - Disasters in the inner city. PMID- 1747663 TI - Postoperative feeding. PMID- 1747664 TI - The rise of post-traumatic stress disorders. PMID- 1747666 TI - Voluntary confidential audit of outcome of surgery. PMID- 1747665 TI - Seven stages of audit. PMID- 1747667 TI - Oral iron chelation is here. PMID- 1747668 TI - Camelford revisited. PMID- 1747669 TI - Tomorrow's biotechnology. PMID- 1747670 TI - Restraint of children in cars. PMID- 1747671 TI - Vision screening in preschool children: comparison of orthoptists and clinical medical officers as primary screeners. AB - OBJECTIVE: To see if there were differences in referral rates and abnormalities detected from two areas that were operating different preschool vision screening programmes. DESIGN: Cohort study using case notes of referrals. SETTING: Community based secondary referral centres in the county of Avon. PATIENTS: 263 referrals from a child population of 7105 in Southmead district, an area that used orthoptists as primary vision screeners; 111 referrals from a child population of 2977 in Weston-super-Mare, an area that used clinical medical officers for screening. MAIN OUTCOME MEASURES: Amblyopia and squint detection rates, together with false positive referral rates. RESULTS: The amblyopia detection rate in Southmead district was significantly higher than in Weston super-Mare (11/1000 children v 5/1000), as was the detection rate of squint (11/1000 v 3/1000). However, the false positive referral rate from Southmead was significantly lower than that from Weston-super-Mare (9/1000 v 23/1000). CONCLUSION: Preschool vision screening using orthoptists as primary screeners offers a more effective method of detecting visual abnormalities than using clinical medical officers. PMID- 1747672 TI - Dynamics of spread of HIV-I infection in a rural district of Uganda. AB - OBJECTIVE: To define the geographical distribution of HIV infection and the community characteristics associated with HIV prevalence in a rural population of Uganda. DESIGN: Seroprevalence survey and interviews of the population aged 13 years and older in 21 randomly selected clusters. SETTING: Rural population of Rakai district, south west Uganda. SUBJECTS: 1292 adults, of whom 594 men and 698 women gave a blood sample and answered the questionnaire. MAIN OUTCOME MEASURES: HIV status determined by ELISA and western blotting in relation to community characteristics. RESULTS: The weighted seroprevalence of HIV for the district was 12.6% with prevalence by cluster varying from 1.2% to 52.8%. Seroprevalence was highest in main road trading centres (men 26%, women 47%), intermediate in rural trading villages on secondary roads (men 22%, women 29%), and lowest in rural agricultural villages (men 8%, women 9%). For both men and women, multiple regression showed a strong negative association between cluster seroprevalence and the proportion of the population employed in agriculture (beta = -0.677 for men, -0.807 for women). Among women, cluster seroprevalence increased with a higher proportion of the population reporting multiple sex partners (beta = 0.814), external travel (beta = 0.579), and injections (beta = 0.483). CONCLUSIONS: Community characteristics, particularly the proportion of the population in agriculture, are associated with HIV prevalence and can be used for targeting interventions. The seroprevalences of HIV suggest spread of infection from main road trading centres, through intermediate trading villages, to rural agricultural villages. PMID- 1747673 TI - Serum sialic acid concentration and smoking: a population based study. PMID- 1747674 TI - Surveillance of antibiotic resistance in clinical isolates of Neisseria gonorrhoeae. PMID- 1747675 TI - Urinary incontinence: prevalence, need for treatment, and effectiveness of intervention by nurse. AB - OBJECTIVE: To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN: Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING: One urban and one rural general practice in Somerset. SUBJECTS: 7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION: Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES: Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS: The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS: About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training. PMID- 1747676 TI - Unstable asthma and theophylline. PMID- 1747677 TI - Medicine in Europe. 1992 and all that. PMID- 1747678 TI - ABC of vascular diseases. Assessment of leg ischaemia. PMID- 1747679 TI - Dangers of ozone depletion. PMID- 1747680 TI - Impact resistance of drinking glasses. PMID- 1747681 TI - Dietary reduction of serum cholesterol concentration. PMID- 1747682 TI - Health of the nation. PMID- 1747683 TI - Estimating the risk of heart attack. PMID- 1747684 TI - Community care for patients with schizophrenia. PMID- 1747685 TI - Threatening miscarriages and new advice on anti-D immunoglobulin. PMID- 1747686 TI - Advertising infant formulas in hospitals. PMID- 1747687 TI - Education on AIDS during biology classes. PMID- 1747688 TI - Privatisation on parade. PMID- 1747689 TI - A gauntlet for senior house officers. PMID- 1747690 TI - US lowers lead limits. PMID- 1747692 TI - Visiting other departments. PMID- 1747691 TI - Joint replacement in the 1990s. PMID- 1747693 TI - Outcome of parenteral gold therapy in RA patients: a comparison between two periods using life-table analysis. AB - Tolerance and outcome of parenteral gold therapy were compared using life-table analysis and ARA remission criteria between 151 rheumatoid arthritis (RA) patients treated in 1983 and in 210 patients treated in 1985. The total risk of termination of therapy was significantly higher in patients treated in 1983 than those treated in 1985. The most common causes were mucocutaneous reactions (41 and 25% in 1983 and 1985, respectively), unsatisfactory effect (15 and 25%) and practical problems (14 and 26%). The outcome regarding all ARA remission criteria except for fatigue (not systematically registered) was significantly more favourable in patients treated in 1985 than in those treated in 1983. PMID- 1747694 TI - How should I treat a 24-year-old female with a 6-year history of relapsing polychondritis, mainly affecting the nasal cartilage, and to a lesser extent the auricular cartilages? PMID- 1747695 TI - Insidious loss of renal function in patients with anticardiolipin antibodies and absence of overt nephritis. AB - Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA. PMID- 1747696 TI - Joint space in radiologically normal knees. AB - Joint space loss is a characteristic feature of rheumatoid arthritis and osteoarthritis. It cannot be fully evaluated, however, without knowledge of the normal variability of joint space size. We have measured joint space size using digital image analysis in a population of radiologically normal individuals. Anteroposterior films of the knee were studied from 685 consecutive patients attending Casualty with unexplained knee pain or following trauma, but with no clinical or radiological evidence of arthritis. Results show that in a radiologically normal population, men have larger joint spaces than women and there is a steady decline in joint space size with age. We found no significant difference in joint space size between weight bearing and non-weight bearing women. There was also no difference in patients presenting with pain and those presenting following an injury. Normal joint space size was not related to height, weight or body mass index in a subgroup of 213 patients. We suggest that patients lose joint space with increasing age and eventually reach a 'pain threshold' at which symptoms of osteoarthritis occur. This explains the increase in joint symptoms in those who begin with smaller joint spaces; that is in women and in the elderly. PMID- 1747697 TI - Antinuclear antibodies in first-degree relatives of patients with polymyositis dermatomyositis: analysis of the relationship with HLA haplotypes. AB - Antinuclear antibodies (ANA), as detected by indirect immunofluorescence on HEp-2 cells, have been investigated in five spouses and 41 first-degree relatives of nine probands with polymyositis-dermatomyositis (PM-DM) and in 41 sex- and age matched controls. ANA were detected in 12 out of the 41 first-degree relatives and in two controls (chi 2 = 6.97; P less than 0.01). HLA typing was done in four out of the nine families; in two of them only, ANA segregated with a haplotype. ANA positivity was not correlated either to sex or to age or to household contact. Our results show that ANA occur in a significant percentage of first degree relatives of patients with PM-DM. The finding seems to be genetically conditioned. PMID- 1747698 TI - Factor VIII von Willebrand factor antigen levels correlate with symptom severity in patients with Raynaud's phenomenon. AB - We have previously documented raised levels of factor VIII von Willebrand factor antigen (FVIII vWF Ag), an endothelial product, in patients with vascular diseases and suggested that levels of this relate to disease activity. No one has yet investigated patients with Raynaud's phenomenon (RP) alone to see if the severity of vasospastic attacks relates to FVIII vWF Ag. We studied 22 patients with RP. None of these patients fulfilled diagnostic criteria for a connective tissue disease but all had severe symptoms which warranted referral to hospital. We measured the FVIII vWF Ag and the procoagulant factor VIII (FVIII:c) levels in these patients. FVIII:c is not an endothelial product and is released by different mechanisms, thus it forms an active control to FVIII vWF Ag. FVIII vWF Ag measurements were carried out using the Laurell method and FVIII:c was assessed using the technique described by Nilsson. Patients were asked to complete diaries over a 2-week winter period. The frequency and duration of all Raynaud's attacks were recorded. There were significant positive correlations between FVIII vWF Ag and the total number and duration of RP attacks over the 2 week period (P less than 0.005, r = 0.67 and P less than 0.05, r = 0.40, respectively; Spearman's rank correlation). No correlation was found between levels of FVIII:c and the same clinical parameters. It has been suggested that patients with clinical evidence of vascular damage have elevated plasma levels of FVIII vWF Ag. Our present study has demonstrated correlations between FVIII vWF Ag levels and the clinical severity of vasospasm in patients with RP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747699 TI - Is there a place for corticosteroid injection in the management of Achilles' tendon lesions? PMID- 1747700 TI - Primary Sjogren's syndrome in north east England--a longitudinal study. AB - We have documented the initial clinical features of 100 patients with primary Sjogren's syndrome (SS) together with the results of their baseline investigations. The evolution of the disease in these patients has been followed for a median of 34 months (range 3-84 months). The majority of patients were females aged 40-60 years, and common clinical features included eye symptoms (100%), xerostomia (100%), polyarthralgia (94%), Raynaud's phenomenon (81%) and salivary gland swelling (47%). Thyroid disease was relatively common (14%) while other endocrine disease was rare. Four patients died during follow-up, and three cases of lymphoma were detected. Other serious complications included pericarditis (10%), pleuroparenchymal lung disease (9%), renal tubular acidosis (3%) and cerebrovascular accidents (2%). The presence of anti-Ro antibodies identifies patients with more severe systemic disease. Spontaneous improvement occurred in 12 patients, while steroids were required for specific complications in 18. Overall, although lymphoma was found to excess in our group, the high mortality reported with primary SS elsewhere was not seen. PMID- 1747701 TI - Single cell imaging reveals abnormal intracellular calcium signals within rheumatoid synovial neutrophils. AB - Intracellular calcium (Ca2+) signalling in synovial fluid (SF) polymorphonuclear leucocytes (PMN) from patients with rheumatoid arthritis (RA) was compared to RA and normal circulating blood PMN using single cell imaging. RA SF PMN stimulated by the peptide f-Met-Leu-Phe (FMLP) showed a striking difference in the release of Ca2+ from the intracellular store compared to RA and normal circulating blood PMN. Stimulation caused the release of a very dispersed, nonrestricted 'cloud' of Ca2+ in 60% of RA SF PMN compared to the highly localized and restricted 'cloud' observed in only 30% of normal circulating PMN. In the presence of extracellular Ca2+, both RA SF and normal blood PMN showed heterogeneity in both the timing and magnitude of their cytosolic free Ca2+ signalling. These observations imply that the Ca2+ signalling mechanism in RA SF and RA blood PMN has been primed in a way which could exacerbate the release of inflammatory mediators. This may have serious implications for explaining the aberrant behaviour of SF PMN in RA. PMID- 1747702 TI - Should disease-modifying agents be used in mild rheumatoid arthritis? AB - A 12-month double-blind controlled study comparing hydroxychloroquine 400 mg daily with placebo in 104 patients with mild RA was conducted to see whether patients with mild rheumatoid arthritis (RA) benefit from treatment with disease modifying agents. Mild RA was defined as synovitis limited to the hands and feet, an ESR less than 30 mm/h and C-reactive protein less than 20 mg/l, a situation where accepted clinical practice is to use a non-steroidal anti-inflammatory agent alone. By 6 months, the improvement of clinical and laboratory parameters in the hydroxychloroquine treated patients was significant compared with pretreatment levels and significantly greater than the control group. This improvement was maintained at 12 months. In addition, fewer patients withdrew through lack of efficacy, eight on hydroxychloroquine versus 18 on placebo. The implications of treating this well defined group of patients is discussed. PMID- 1747703 TI - Arthritis artefacta: factitious disease in rheumatology. AB - Self-induced disease can be difficult to diagnose and costly of time and money to investigate. The key is to think of the possibility. Five patients in whom the evidence for factitious rheumatological illness was strong are discussed and their histories, physical signs and family backgrounds are explored in relationship to factitious disease presenting in other fields. Young immature individuals seem most at risk and the discrepancy between physical signs and understandable pathological mechanisms may suggest the diagnosis. The outlook seems frequently poor. PMID- 1747704 TI - A preliminary study of magnetic resonance relaxation times (T1 and T2) in inflammatory and degenerative synovial fluids. AB - Multiple synovial fluid samples from 21 patients were analysed using standard synovial analysis techniques and by nuclear magnetic resonance spectroscopy. Significant negative correlations were noted between both T1 (P less than 0.01) and T2 (P less than 0.0006) relaxation times and synovial fluid total protein. No differences in T1 or T2 relaxation times were noted in synovial fluid between 16 patients with inflammatory forms of arthritis and five patients with degenerative arthritis. In a single rheumatoid arthritis patient with concurrent staphylococcal arthritis, T1 and T2 relaxation times did not vary between the active phase and the recovery phase. The lack of any significant differences in the measured relaxation times as a function of joint condition suggest that in vivo magnetic resonance measurements of T1 or T2 for joint analysis may not reveal information of either a diagnostic or pathophysiological nature. PMID- 1747705 TI - Carpal tunnel syndrome complicated by reflex sympathetic dystrophy syndrome. AB - This report describes three patients with reflex sympathetic dystrophy complicating carpal tunnel syndrome. Pain disproportionate and more diffuse than that commonly associated with carpal tunnel syndrome suggested the associated diagnosis in each patient and facilitated prompt management. PMID- 1747706 TI - Malignant hypertension and antiphospholipid antibodies as presenting features of SLE in a young woman using oral contraceptives. AB - A 24-year-old woman developed malignant hypertension while on oral contraceptives (OCs). She was found to have incomplete systemic lupus erythematosus (SLE) with DNA antibodies and high levels of antiphospholipid antibodies (APLA). She later developed SLE and has had three miscarriages and a cerebellar infarction. PMID- 1747707 TI - Transient erosion of the ulnar styloid process. AB - A patient with polyarthritis had radiographs of the wrists taken at presentation and again at 6 months. At presentation radiographs were normal, but repeat X-rays at 6 months showed complete erosion of both ulnar styloid processes. This did not correlate with the clinical picture of a mild synovitis. A third X-ray showed normal wrists, revealing the cause to be a positional artefact during the X-ray procedure. Clinicians should be aware of this 'catch'. PMID- 1747708 TI - Reiter's syndrome and reactive arthritis. PMID- 1747710 TI - Role of prolactin in autoimmune diseases and autoimmunity. PMID- 1747709 TI - Pneumocystis carinii pneumonia causing hypertrophic osteoarthropathy. PMID- 1747711 TI - Genetics of rheumatoid arthritis. PMID- 1747713 TI - Does the weather affect the osteoarthritic patient? PMID- 1747712 TI - Assessment of disability in male and female rheumatoid patients. PMID- 1747714 TI - Psoriatic spondylitis presenting as chronic torticollis. PMID- 1747715 TI - The investigation of impotence. PMID- 1747716 TI - Hyperoxaluria in patients with recurrent calcium oxalate calculi: dietary and other risk factors. AB - The presence of mild hyperoxaluria in recurrent calcium oxalate stone formers is controversial. The aim of this study was to identify recurrent stone formers with mild hyperoxaluria and to classify them further by assessing their response to a low oxalate diet. In addition, the prevalence of other risk factors for stone formation in this group of patients was investigated. A total of 207 consecutive patients with recurrent renal calculi were screened and 40 (19%) were found to have mild hyperoxaluria. Of these, 18 (45%) responded to dietary oxalate restriction by normalising their urinary oxalate. The remaining 22 patients were classified as having idiopathic hyperoxaluria and were subdivided into those in whom urinary oxalate excretion was consistently elevated in all specimens measured and those in whom the elevation was intermittent in nature. Dietary oxalate restriction had a partially beneficial effect in lowering oxalate excretion in the patients with persistent hyperoxaluria. No difference in urinary oxalate excretion was found after dietary restriction in the patients with intermittent hyperoxaluria. Other risk factors, including dietary, absorptive and renal hypercalciuria and hypocitraturia, were documented, the prevalence of which (65%) was not significantly different from that (62.5%) found in 40 age- and sex matched calcium stone formers without hyperoxaluria. The prevalence of hyperuricosuria was significantly greater in patients with hyperoxaluria when compared with stone controls. Further studies are required to elucidate the underlying mechanisms of hyperoxaluria in recurrent stone formers. PMID- 1747717 TI - Renal function after partial nephrectomy with the Nd-YAG laser. Experimental study in piglets. AB - Twelve partial nephrectomies were performed in 12 piglets using either the combination (contact and non-contact) Nd:YAG laser technique or a steel scalpel. Additional haemostasis was attempted with ligatures. The renal artery was not clamped and renal cooling was not attempted. Total nephrectomy was performed on the contralateral side. Serum creatinine and urea levels were measured, and 99mTc DTPA renography was performed pre-operatively and 1 and 2 weeks post-operatively. One week post-operatively the mean serum creatinine level was 35% higher than the pre-operative level in the laser group and 30% higher in the steel scalpel group. Two weeks post-operatively the respective differences were 34 and 24%. The mean urea level 1 week after operation was 50% higher than the pre-operative level in the laser group and 17% higher in the steel scalpel group. Two weeks post operatively the respective differences were 38% in the laser group and 20% in the steel scalpel group. The mean DTPA disappearance rate was 34% lower 1 week after operation in the laser group and 23% lower in the steel scalpel group when compared with the preoperative state. Two weeks post-operatively the respective changes were 48 and 25%. These data indicate that there is no significant difference in renal function when the Nd: YAG combination laser technique is used in partial nephrectomy as compared with the steel scapel. PMID- 1747718 TI - Pyonephrosis and renal abscess associated with kidney tumours. AB - Whilst the diagnosis of pyonephrosis and renal abscess is fairly easy, the source of obstruction and infection is an important indicator of treatment. The association of kidney tumours with these inflammatory manifestations has not previously been emphasised. Reviewing our cases of pyonephrosis and renal abscesses, we report 4 patients with concomitant tumours of the kidney and discuss their management. PMID- 1747719 TI - Renal hydatid disease. AB - Hydatid disease is caused by the larval form of Taenia echinococcus (Echinococcus granulosus) in humans, the most common sites being the liver and the lungs. Involvement of the kidneys is uncommon and can be asymptomatic for long periods. Renal hydatid disease has no pathognomonic signs except for hydatiduria. Because of the risk of fatal anaphylaxis, puncture of the cyst should be avoided, and partial or total nephrectomy is still the preferred treatment. We present 10 patients with renal hydatid disease treated in the Department of Urology, Ankara University. PMID- 1747720 TI - Comparison of clinical and pathological characteristics in incidentally detected and suspected renal carcinoma. AB - In a study of the clinical and pathological characteristics of incidentally detected and suspected renal carcinoma, we reviewed the manner of presentation, serum immunosuppressive acidic protein (IAP), tumour stage and size in 112 consecutive patients with renal carcinoma who were diagnosed clinically and surgically between 1980 and 1989. The results showed an increase in the proportion of incidentally diagnosed cases. The routine use of radiological imaging, especially ultrasound and computed tomography (CT), has led to tumours being diagnosed earlier than when IAP is used as a tumour marker in patients with incidentally detected renal carcinoma. Tumours were lower stage and smaller in patients with incidentally detected renal carcinoma than in patients in whom the diagnosis was suspected. PMID- 1747721 TI - Sex distribution of adult idiopathic detrusor instability in relation to childhood bedwetting. AB - The urodynamic case records of 1000 consecutive men and women were reviewed to study the link between idiopathic detrusor instability (DI) and childhood nocturnal enuresis and to determine whether a sex difference in this relationship may exist. Idiopathic DI was found in 10% of the men, 63% of whom had suffered from childhood bedwetting; 29% of the women had idiopathic instability, of whom 38% had been nocturnal enuretics. Thus the link between adult idiopathic DI and childhood bedwetting appeared to be stronger for men than for women. The sex distribution of subjects is not always reported in urodynamic studies of bedwetters and adults with an unstable bladder. We suggest that this should become routine practice as it may help to shed light on the aetiology of idiopathic detrusor instability. PMID- 1747722 TI - Subtrigonal phenol injection. How safe and effective is it? AB - A series of 24 patients underwent 27 transtrigonal phenol injections for the treatment of bladder instability. Only 2 of 18 patients with detrusor instability and 2 of 6 with detrusor hyperreflexia continued to derive benefit from the procedure 6 months after it was carried out. Serious complications attributable to phenol were seen in 2 patients in this series and in a further 4 patients referred for complications resulting from this therapy in other centres. These results and a review of the literature lead us to suggest that transvesical phenol injection should not be used except in the hyper-reflexic bladder when no alternative treatment is possible. Particular care should be exercised in patients who have undergone extensive prior surgery or radiotherapy. PMID- 1747723 TI - Clam ileocystoplasty. AB - Clam enterocystoplasty has been used successfully in the treatment of refractory urge incontinence. We report 31 patients who underwent ileocystoplasty between 1982 and 1989. The majority of patients were pleased with the outcome of the operation. The main post-operative complication was voiding dysfunction due to relative bladder outflow obstruction. Urinary tract infection and mucus production were significant long-term problems. PMID- 1747724 TI - Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity. AB - A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy. PMID- 1747725 TI - How effective is topical alpha-2b interferon in preventing recurrence of superficial bladder cancer? AB - A total of 44 patients with low and intermediate grade superficial urothelial bladder cancer Ta and T1 were randomised into a controlled, long-term, phase III trial on topical instillation therapy with high dose alpha-2b interferon (100 x 10(6) IU versus low dose alpha-2b interferon (10 x 10(6) IU) versus ethoglucid. Thirteen patients in the low dose group, 11 in the high dose group and 10 in the ethoglucid group completing the trial were evaluable (median follow-up 36.5 months) and were followed up for 3 years. They were treated weekly for 10 weeks and then monthly for a total of 1 year. The aim of the trial was to establish the prophylactic efficacy and the toxic side effects, if any, of alpha-2b interferon in the topical treatment of superficial bladder cancer. Recurrence rate and disease-free survival were chosen as study end-points. The recurrence rate was 4.4 in the low dose interferon group, 2.76 in the high dose interferon group and 3.08 in the ethoglucid group. In the low dose interferon group the time to the first recurrence was 22.23 months versus 22.36 in the high dose group and 21.76 months in the ethoglucid group. No differences of statistical significance were noted between the 3 groups. Progression occurred in 5 patients on interferon but was not seen in those on ethoglucid. Neither systemic nor local side effects were seen in the interferon groups, but 3 patients had to be taken off ethoglucid because of severe chemocystitis. In superficial bladder cancer, topical instillation therapy with interferon is as effective as conventional chemotherapy and has no side effects. PMID- 1747726 TI - Relationship between clinical stage and histological zone of origin in early prostate cancer: morphometric analysis. AB - A detailed morphometric analysis of 96 radical prostatectomy specimens (13 clinical stage A1, 29 A2, 34 B1 and 20 B2) was undertaken to examine the relationship of zone of origin to volume, grade and extraprostatic extension of cancer. In patients with stage A disease, transition zone (TZ) cancer (present in 81%) was significantly larger but of lower grade than peripheral zone (PZ) cancer (present in 90%). The total volume of cancer in stage A1 patients averaged 1.55 ml with 72% of TZ origin. In patients with stage A2 disease, tumour volume averaged 5.83 ml with only 57% of TZ origin. Specimens taken during transurethral resection of the prostate (TURP) revealed TZ cancer in 82% and PZ cancer either alone or with TZ cancer in 22%. The 9 patients with PZ cancer in the TURP specimen included 5 of the 11 with extracapsular extension and all 5 of those with seminal vesicle invasion. Every patient with stage B disease had PZ cancer which, in all except 3 cases, was of significantly larger volume and higher grade than any TZ cancer (present in 43%) in the same gland. In patients with stage B cancer, total tumour volume was 5.13 ml with 91% of PZ origin. TZ cancer tended to be well differentiated in all patients, even at large volumes, whereas PZ cancer was often moderately or poorly differentiated even at low volumes. In patients with stage B disease, TZ cancer appeared to be incidental and of no clinical importance, while in stage A patients PZ cancers were sometimes large, poorly differentiated and extended outside the prostate. Progression of a stage A cancer seems more likely to result from PZ cancer than TZ cancer, and the finding of PZ cancer in a TURP specimen should probably preclude its classification as stage A1. PMID- 1747727 TI - Unusual foreign bodies in the urethra and bladder. AB - We report 8 cases of self-inserted unusual foreign bodies in the lower urinary tract, all being treated from 1976 to 1990. Three of them were located in the urethra and 5 in the bladder. Several objects were found (electric cable, tweezers, hairpin, drawing pin, pebbles, paper clip). In 4 cases the objects were inserted for masturbatory purposes. Five of the patients were psychologically ill or handicapped. The most common reason for consultation was dysuria, and the treatment procedures were endoscopy in 5 patients and cystotomy in the other 3. PMID- 1747728 TI - Surgical technique for inguinal surgery and its effect on fertility in the Wistar rat model. AB - This study has explored the relatively neglected effects of operative manipulation of the vas deferens on fertility. Following unilateral vasectomy the contralateral vasa of 52 4-week-old Wistar rats were subjected to 7 different manipulations. After 7 weeks a fertility trial was conducted. All sham operated rats (n = 18) were fertile. Of the remaining 34 rats, 22 (65%) were sterile. All of those with tight ring reconstruction (n = 6) were sterile, due initially to venous obstruction. Nine of 14 rats with acute clip trauma (65%) remained fertile but 11 of 14 (78%) with full mobilisation were sterile owing to extensive avascular fibrosis of the vas deferens. These results suggest that overzealous cord handling and operative technique in the immature animal is counterproductive and leads to vasal occlusion. This may have important repercussions in paediatric inguinal surgery, with a subsequent higher incidence of azoospermia and male subfertility. PMID- 1747729 TI - Microsurgical epididymovasostomy by loop intussusception. A new technique in the rat model. AB - A new technique, epididymal loop intussusception into the vas deferens, is offered as an improved form compared with the side-to-end method. Loop intussusception has been experimentally studied bilaterally in 15 adult male rats. This report provides details of the technique. A 3-month anatomical and histological follow-up showed a 100% patency rate, no anastomotic stricture, and reabsorption of the blind intussuscepted loop in all but 3 cases. Macroscopic sperm granulomas were present in only 10% of the anastomoses examined. Advantages and disadvantages of microsurgical epididymovasostomy techniques are discussed. PMID- 1747730 TI - Animal models for epididymoepididymostomy. Development of an alternative microsurgical procedure for vasoepididymostomy. AB - The present success rate for high level microsurgical vasoepididymostomy in patients with obstructive azoospermia is generally poor in comparison with more distal vasoepididymal bypasses, suggesting that the development of a high level bypass method which preserves the distal maturation and storage functions of the epididymis might increase the fertility success rate. To achieve this we have developed a segmental bypass of the distal caput-proximal corpus regions of the epididymis (epididymoepididymostomy) using the rat and rabbit as animal models. In this procedure the epididymides of 11 adult male Sprague-Dawley rats were exposed through a scrotal incision and a convolution of the duct in the proximal corpus region was attached to an opened convolution in the mid-caput epididymides using a standard microsurgical technique. Each male was rested for at least 3 months after the microsurgical bypass operation to allow the preoperative sperm contents of the caudal storage region to be replaced by post-bypass spermatozoa. Six of the 11 rats were proven fertile after surgery by siring litters from mating trials up to 11 months later. The patency of anastomoses was confirmed in 3 animals by laparotomy and recovery of large numbers of sperm with normal motility from the cauda epididymidis distal to the anastomosis site and also from the vas. Similar unilateral surgery in 2 adult male rabbits resulted in normal post-operative semen profiles in 1 and an in vivo fertilisation rate of 100% from 1 mating trial 8 months after surgery. The successful development of a reliable animal model for epididymoepididymostomy provides an experimental tool for studying the function of the epididymis. This technique may also have clinical application as an alternative to high level vasoepididymostomy in selected patients with obstructive azoospermia. PMID- 1747731 TI - Seminal white blood cells in men with urethral tract infection. A monoclonal antibody study. AB - Monoclonal antibodies were used to detect seminal leucocytes in 19 men with urethritis. A wide range in the number and type of leucocytes between individuals was documented (median 2.06 x 10(6)/ml, range 0.6-29.89 x 10(6)/ml); 22% of the men had less than 1 x 10(6) leucocytes/ml. The results suggest that the threshold of greater than or equal to 1 x 10(6)/ml proposed by the World Health Organisation to indicate genital tract infection is unsuitable for men with urethritis. PMID- 1747732 TI - The role of colour duplex ultrasonography in the diagnosis of vasculogenic impotence. AB - Colour duplex ultrasonography was used to obtain peak systolic velocity (PSV) readings from cavernosal arteries at rest and during papaverine-induced tumescence. Results from 31 men with vasculogenic impotence were compared with those from 17 men with non-vasculogenic impotence and a control group of 6 potent men. In the flaccid state no significant differences in PSV readings were found between the vasculogenic and control groups. Following the injection of papaverine, men from the vasculogenic group without venous leakage were alone in having significantly lower PSV readings compared with the potent controls. All 23 men with normal penile haemodynamics had a mean PSV greater than or equal to 20 cm/s during tumescence. This was also the case for 19 (61%) of the vasculogenic group, including 9 (69%) of the 13 patients with venous leakage. The remaining 12 men in the vasculogenic group (39%) had a mean PSV less than 20 cm/s, this being diagnostic of an inadequate arterial inflow. Colour duplex ultrasonography can identify patients who have marked arterial insufficiency as the major cause of their impotence and hence allows more rational selection for angiography and revascularisation. Lesser degrees of arterial deficit are difficult to characterise using mean PSV readings alone. PMID- 1747733 TI - Urinary stone formation in children with prenatally diagnosed uropathies. AB - Among a series of 312 patients with prenatally diagnosed uropathies, 4 male children developed urinary calculi at ages varying from 2 to 5 years. All had upper urinary tract dilatation not associated with vesicoureteric reflux or with renographically defined obstruction; 3 followed Proteus urinary infections. Strategies for prevention are discussed. PMID- 1747734 TI - Surgical management of incontinence in bladder exstrophy. AB - Between 1978 and 1990, 86 patients with previously closed classical bladder exstrophy and 10 patients seeking undiversion have presented for continence management and have undergone selective reconstruction designed for voiding and/or intermittent urethral catheterisation. The reconstruction in these 96 patients has been reviewed. Eight of the 10 patients undergoing undiversion achieved a satisfactory state of continence but 4 required Mitrofanoff procedures to enable catheterisation. Of the other 86 patients, 2 reached a satisfactory state of continence without further surgery; 79 underwent bladder neck surgery for continence either without augmentation (n = 32) or with augmentation (n = 47). Twenty of the 32 patients who were treated by bladder neck reconstruction alone were later found to require augmentation. Five patients had very early augmentation either to facilitate neonatal closure or on account of severe upper tract dilatation. Of these, 1 became continent without further surgery and 4 demonstrated the need for bladder neck reconstruction. Thus 12 children achieved successful continence (n = 6) or are evolving satisfactorily with potential success (n = 6) as a result of bladder neck reconstruction. Of the 71 patients requiring bladder neck reconstruction and augmentation, 68 have completed their surgery. The current status of these patients is: satisfactory in 57 (80%) (42 void/urethral clean intermittent catheterisation (CIC), 7 waiting to learn CIC, 5 Mitrofanoff, 3 artificial urinary sphincter (AUS]. Of the remaining 11 patients (20%), 8 are unsatisfactory to varying degrees and the status of the other 3 is unknown. PMID- 1747735 TI - Unusual presentation of a testicular tumour. PMID- 1747736 TI - Candida albicans infection in solitary kidney presenting as anuria. PMID- 1747737 TI - Primary lymphoma of the bladder arising from an area of Malakoplakia. PMID- 1747738 TI - Priapism in haemodialysis patient due to prazosin? PMID- 1747739 TI - Partial extraction of double-J stent during nephrostomy tube removal and its prevention. PMID- 1747740 TI - Filling defects of infectious origin in the cystogram of a 6-year-old child. PMID- 1747741 TI - Chronic urinary retention masquerading as meralgia paraesthetica. PMID- 1747742 TI - Urinary tract infections: the need for pure culture technology in clinical laboratory diagnosis. PMID- 1747743 TI - Electrophysiological responses to muscarinic receptor stimulation in cultured hippocampal neurons. AB - Electrophysiological recordings of responses to muscarinic receptor stimulation in cultured embryonic hippocampal neurons have been largely unsuccessful to date. In this study muscarinic receptor binding was demonstrated in 2-week-old embryonic rat hippocampal cultures. Using whole-cell patch-clamp recording we found that 1-5 microM carbachol produced multiple effects including depolarization, increased action potential firing rate, increased synaptic activity and a reduction in the amplitude of medium-duration afterhyperpolarizations. Voltage-clamp analysis revealed a time-dependent current relaxation with hyperpolarizing steps from a holding potential of about -40 mV which was inhibited by 10 microM muscarine or 50 microM carbachol and had characteristics similar to those of the m-current. Both atropine and pirenzepine inhibited all of these effects indicating that these cholinergic actions were mediated by muscarinic receptors. This study shows that muscarinic responses obtained classically in hippocampal brain slices can also be produced in cultured hippocampus. PMID- 1747744 TI - Inhibition of NMDA-induced protein kinase C translocation by a Zn2+ chelator: implication of intracellular Zn2+. AB - The role of intracellular Zn2+ in the translocation of protein kinase C from cytosol to membrane fractions was examined by the [3H]phorbol 12,13-dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. N-methyl-D aspartate (NMDA, 100 microM) and calcium ionophore A23187 (0.3-30 microM) decreased the binding activity in the cytosol with a concomitant increase in the membrane fractions. Pretreatment of synaptoneurosomes with a heavy metal chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), inhibited the NMDA- and A23187-induced changes of the distribution of [3H]PDBu binding sites in cytosol and membrane fractions. The inhibitory effect of TPEN was negated by a preincubation of TPEN with equimolar Zn2+ but not by that with Ca2+. The addition of 500 microM Zn2+ to the lysate of synaptoneurosomes induced an increase of [3H]PDBu binding activity in the membrane fraction with a concomitant decrease in the cytosol fraction, as did 100 microM Ca2+. Low concentrations of Zn2+ (10 microM), which alone had no effect on the distribution of the binding, significantly enhanced the effect of 10 microM Ca2+ in the lysate. Under those conditions TPEN inhibited the Zn(2+)-potentiated Ca(2+)-dependent changes in the binding. These results suggest that intracellular Zn2+ is essential for the agonist-induced translocation of protein kinase C in guinea pig synaptoneurosomes. PMID- 1747745 TI - Age effects on monoamine turnover of the rat substantia nigra. AB - Measurement of turnover of dopamine (DA), noradrenaline (NA) and serotonin (5 hydroxytryptamine (5-HT), and their metabolites has been performed in 6- and 24 month-old rats. Dopamine synthesis in 24-month-old rats did not show any change with respect to 6-month-old rats. However, our results seem to indicate decreased DA release in 24-month-old rats. This hypothesis could be supported by the changes found in the 3-methoxytyramine (3-MT) accumulation rate after monoamine oxidase inhibition with pargyline. The turnover of NA and its main metabolite, 3 methoxy-4-hydroxyphenylglycol (MHPG) decreased in 24-month-old rats compared with 6-month-old rats. Serotonin synthesis did not change in 24-month-old rats with respect to 6-month-old rats. However, the metabolism of 5-HT quantified as turnover of 5-hydroxy-3-indoleacetic acid (5-HIAA) increased in 24-month-old rats with respect to 6-month-old rats. The monoamine oxidase B:monoamine oxidase-A ratio increased in 24-month-old rats. The significance of these changes is discussed. PMID- 1747746 TI - Chronic ethanol ingestion decreases vasopressin mRNA in hypothalamic and extrahypothalamic nuclei of mouse brain. AB - Endogenous arginine vasopressin was previously shown to modulate the rate of loss of functional (CNS) tolerance to ethanol, suggesting that chronic ethanol ingestion might alter vasopressin synthesis and/or release. Since extrahypothalamic vasopressin is believed to be involved in the CNS effects of the peptide, we determined the effect of ethanol on vasopressin mRNA in the bed nucleus of the stria terminalis (BST), as well as in several hypothalamic nuclei. Chronic ethanol ingestion, that produced functional tolerance and physical dependence in mice, resulted in decreased vasopressin mRNA levels in all areas examined. In contrast, as expected, dehydration resulted in increases in vasopressin mRNA in the BST and in all hypothalamic nuclei except the suprachiasmatic nucleus. In the BST, both ethanol ingestion and dehydration affected cells in the central region of the nucleus, while cells in the caudal portion were only affected by ethanol treatment. The results indicate that chronic ethanol ingestion generally reduces the synthesis of vasopressin, and that increased vasopressin synthesis is not necessary in order for the peptide to affect ethanol tolerance. PMID- 1747747 TI - Asymmetric sigmoid non-linearity in the rat olfactory system. AB - The statistical relationship between multi-unit spike activity and simultaneously recorded local dendritic field potentials in the olfactory system of the waking rat was studied with chronically placed electrodes. The relationship had the form of a sigmoid increase in axonal firing probability conditional on the amplitude of dendritic potentials. These data were fitted with an asymmetric sigmoid curve previously derived from the Hodgkin-Huxley equations. The curve was fitted using non-linear regression to optimize its parameter: the maximal firing rate. The maximal rate also gave the steepness of the slope of the sigmoid. Pulse trains were recorded from excitatory and inhibitory neurons in the olfactory cortex (including the anterior olfactory nucleus, the prepyriform cortex and the lateral entorhinal area) as identified by the phase relations of the pulse probability and the dendritic potentials, and from the excitatory neurons in the bulb (the inhibitory granule cells do not give extracellularly detectable action potentials). All these neurons are known to interact in disynaptic negative feedback loops giving rise to oscillations. The same sigmoid function fit the data from both types of neurons in all locations. The curves for neurons in all parts of the olfactory cortex had a 3-fold higher slope and maximal value than the curves from bulbar neurons. The significances of this difference and of the asymmetric sigmoid are discussed in terms of models for olfactory oscillatory dynamics and pattern recognition. PMID- 1747748 TI - Sympathetic neuron factors involved in bradykinin-induced plasma extravasation in the rat. AB - Previous studies have demonstrated that bradykinin (BK) produces a sympathetically dependent plasma extravasation into the rat knee joint which is, in part, dependent upon the production of a prostaglandin. In the present study, co-administration of the specific prostaglandin, PGE2, markedly enhanced the BK induced plasma extravasation. In this study we also report that after chemically induced sympathectomy, by chronic pretreatment with 6-hydroxydopamine (6-OHDA), both the plasma extravasation produced by BK and the enhancing effect of PGE2 are markedly attenuated. Plasma extravasation induced by PGE2 alone was small and was not significantly attenuated by sympathectomy. We conclude that BK-induced extravasation involves production of at least two sympathetic postganglionic neuron (SPGN) terminal-dependent factors, one of which is a cyclo-oxygenase product of arachidonic acid metabolism, probably PGE2, (Coderre et al., J. Neurophysiol., 62 (1989) 45-58) and another that is unidentified. PMID- 1747749 TI - Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat. AB - To study the possible involvement of hypothalamic growth hormone-releasing factor (GRF) in sleep regulation, a competitive GRF-antagonist, the peptide (N-Ac-Tyr1,D Arg2)-GRF(1-29)-NH2, was intracerebroventricularly injected into rats (0.003, 0.3, and 14 nmol), and the EEG and brain temperature were recorded for 12 h during the light cycle of the day. Growth hormone (GH) concentrations were determined from plasma samples taken at 20-min intervals for 3 h after 14 nmol GRF-antagonist. The onset of non-rapid eye movement sleep (NREMS) was delayed in response to 0.3 and 14 nmol GRF-antagonist, the duration of NREMS was decreased for one or more hours and after 14 nmol EEG slow wave amplitudes were decreased during NREMS in postinjection hour 1. The high dose of GRF-antagonist also suppressed REMS for 4 h, inhibited GH secretion, and elicited a slight biphasic variation in brain temperature. These findings, together with previous observations indicating a sleep-promoting effect for GRF, support the hypothesis that hypothalamic GRF is involved in sleep regulation and might be responsible for the correlation between NREMS and GH secretion reported in various species. PMID- 1747750 TI - Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam. AB - The effects of psychological stress on catecholamine and indoleamine metabolism were examined in various brain regions of rats. Psychologically stressed rats were exposed to emotional responses of foot-shocked rats, but were themselves prevented from receiving foot-shock. Psychological stress for 30 min resulted in significant increases of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the medial prefrontal cortex (MPFC), but not in other dopamine (DA) terminal fields. The levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were unaffected in all brain regions examined after 30 min of psychological stress. A small but significant increase of DOPAC levels in the ventral tegmental area (VTA) was observed after a shorter (10 min) duration of stress. Moreover, an increase of DOPAC levels in the MPFC 30 min after psychological stress was attenuated by diazepam (5 mg/kg), and this attenuating effect was antagonized by Ro 15-1788 (15 mg/kg). These results suggest that mesoprefrontal DA neurons are selectively activated by psychological stress, and that the activation of the A10 cell body site (VTA) may precede that of the terminal field (MPFC). Moreover, diazepam was found to possess an inhibitory effect on the activation of mesoprefrontal DA neurons induced by psychological stress, and this effect may be partly mediated by benzodiazepine (BZD) receptors and implicated in the specific anxiolytic action of BZDs. PMID- 1747751 TI - Inhibitory effects of phrenic afferent fibers on primate lumbosacral spinothalamic tract neurons. AB - Studies were conducted to determine if electrical or mechanical stimulation of phrenic afferent fibers (PHR) would inhibit the activity of lumbosacral spinothalamic tract (STT) neurons. Twelve monkeys were anesthetized, paralyzed, and artificially ventilated. Extracellular action potentials were recorded from 78 STT neurons located in L2-S3 spinal segments. Electrical stimulation of PHR reduced the activity of 65%, did not affect 33%, and excited 1% of STT neurons. Mechanical stimulation of the diaphragm reduced the activity of 63%, did not effect 34%, and excited 1% of lumbosacral STT neurons. Distention of the urinary bladder (UBD) inhibited 52%, did not affect 23%, excited 23%, and elicited a biphasic response in 1% of STT neurons. However, there was no correlation between the effect of PHR and UBD or somatic classification of the neurons. We conclude that electrical or mechanical stimulation of PHR can produce a generalized inhibition of lumbosacral STT neurons. This inhibitory effect of PHR is similar to inhibitory effects reported for a variety of other afferent systems. PMID- 1747752 TI - Patterns of cerebellar foliation in recombinant inbred mice. AB - Morphometric analysis of cerebellar foliation patterns at the midsagittal plane was done in the inbred strains BALB/cByJ, C57BL/6ByJ and their 7 recombinant inbred strains in order to assess possible major gene influences. The cerebellum was dissected away from the brainstem and weighed prior to histology so that measures of the depth of fissures and sulci could be related to overall size of the brain and cerebellum. Results for 177 mice revealed that many brains had extra sulci present within the central lobe, the culmen, the declive and the uvula, and that patterns within a genetically uniform inbred strain were highly variable. The measure of sulcus depth was continuous, showing no evidence of a normal versus abnormal dichotomy. Furthermore, the frequency and depth of extra sulci were greater in mice with larger cerebella. Strain differences in size of the whole brain and cerebellum clearly resulted from several genetic loci. This was also true of the extra sulci, except for the declival sulcus which revealed a single gene influence. The gene symbol 'declival sulcus of cerebellum' (dsc) is proposed. PMID- 1747753 TI - Distribution and origin of noradrenergic and serotonergic fibers in the cochlear nucleus and inferior colliculus of the rat. AB - We examined the monoaminergic innervation of the rat cochlear nucleus (CN) and the inferior colliculus (IC) by using retrograde transport of the fluorescent dye Fluoro-Gold combined with immunohistochemistry. We used antisera against the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT), and one against the transmitter serotonin (5-HT). Each substance revealed a distinct pattern of immunoreactive staining in the CN and the IC. In the CN, DBH immunoreactive (-ir) fibers were present in all subnuclei. The molecular layer of the dorsal CN and the granular layer of the ventral CN, however, were largely devoid of DBH-ir fibers. In contrast, 5-HT-ir fibers were abundant in the molecular layer and the granular cell layer of the CN. In the dorsal CN and the postero- and anteroventral CN, however, this innervation was less dense and evenly distributed across subnuclei. In the IC, the DBH-ir fibers were slightly more numerous in layer 2 of the dorsal cortex than in other subnuclei, while the layer 1 of both the dorsal and the external cortex contained only a few fibers. In contrast, the 5-HT-ir fibers formed a dense network in both the dorsal and external cortices of the IC, while they were less abundant in the remaining subnuclei. PNMT-ir fibers were not found in any of the auditory brainstem nuclei. Following Fluoro-Gold injections into the CN or IC, retrogradely labeled DBH-ir neurons were found in the A6 noradrenergic cell group (locus coeruleus). The CN received additional projections from the A5 noradrenergic cell group, as well as sparse projections from the A4 and A7 cell groups. The serotonergic innervation of the CN and IC originated largely in the B7 serotonergic cell group (dorsal raphe nucleus). Serotonergic neurons in other groups of the raphe nuclei were only occasionally labeled. Our data indicate that both noradrenaline and serotonin may play a role in central auditory processing. Their differential distribution in the IC and CN subnuclei suggests that these transmitter systems might influence different functional circuits. PMID- 1747754 TI - Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2). AB - We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard polysomnography. Unlike our previous study in man showing a highly significant 25% decrease in CMRO2 during deep sleep (stage 3-4) we found a modest but statistically significant decrease of 5% in CMRO2 during stage 2 sleep. Deep and light sleep are both characterized by an almost complete lack of mental activity. They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than to mental activity. PMID- 1747755 TI - Modulation of synaptic plasticity in the dentate gyrus of the rat by electrical stimulation of the median raphe nucleus. AB - The effects of median raphe nucleus (MRN) stimulation on the induction of long term potentiation (LTP) was investigated in the dentate gyrus (DG) of urethane anaesthetized rats. LTP of both DG population spike amplitude and population EPSP slope was induced when tetanic electrical stimulation (100 Hz, 1 s) of the perforant path (PP), at an intensity which did not produce significant LTP alone, was presented concurrently with tetanic stimulation of the MRN. Tetanic stimulation of either the PP alone or of the PP and MRN together did not affect the short-term enhancement of population spike amplitude produced by single stimuli to the MRN. These findings suggest that serotonergic afferents from brainstem raphe nuclei may modulate the induction of LTP in the dentate gyrus. PMID- 1747756 TI - Characterization of 4 light-responsive putative motor neurons in the pedal ganglia of Hermissenda crassicornis. AB - As part of the analysis of the circuitry underlying phototaxis, 4 light responsive pedal neurons were identified and characterized. The 4 newly identified neurons have been designated as pedal neurons P7, P8, P9 and P10. Pedal cell P7 has an inhibitory response to light, lasting several minutes. Pedal cells P8, P9 and P10 exhibit excitatory 'on' responses to light that last for a few seconds after light onset. Lucifer yellow fills showed that each identified pedal cell has only one process which exits the nervous system through one of the pedal nerves. Various procedures were used to investigate the responses to illumination expressed by the 4 identified pedal neurons. The results indicate that: (1) the light responses are not intrinsic, but are due to synaptic input from other light-responsive cell(s), and (2) the sources of the synaptic input to the pedal cells are the photoreceptors of the eye, and not extraocular photoreceptors or light sensitive neurons within the circumesophageal nervous system. PMID- 1747757 TI - Intramedullary connections of the rostral nucleus of the solitary tract in the hamster. AB - The rostral nucleus of the solitary tract (NST) figures prominently in the gustatory system, giving rise to ascending taste pathways that are well documented. Less is known of the local connections of the rostral NST with sites in the medulla. This study defines the intramedullary connections of the rostral NST in the hamster. Small iontophoretic injections of horseradish peroxidase (HRP), confined to the rostral NST, resulted in Golgi-like filling of axons that exited the NST or that interconnected cytoarchitectonic subdivisions within the NST complex. The NST efferent axons terminated sparsely in the trigeminal, facial and hypoglossal motor nuclei, but axons and endings were heavily distributed in the parvicellular reticular formation ventral to the NST. HRP injections centered in this part of the reticular formation resulted in heavy projections to the orofacial motor nuclei. Intranuclear connections, labelled after NST injections, linked NST subdivisions that receive primary afferent taste inputs to subdivisions involved in (1) projections to the preoromotor reticular formation, (2) projections to swallowing motor neurons, (3) activation of preganglionic parasympathetic neurons, and (4) general viscerosensation. In general, the connections defined in the present study provide anatomical details about the substrate for gustatory-motor and gustatory-visceral interactions. PMID- 1747758 TI - Calcium deficiency enhances cadmium accumulation in the central nervous system. AB - Weanling male rats were administered 1 of 4 diets for 40 days: control (CONT), low Ca (LOCA), control plus Cd (CONT + Cd) or low Ca plus Cd (LOCA + Cd). After 40 days, Cd was analyzed in 7 brain regions, spinal cord, serum, liver, kidney, muscle and femur by atomic absorption spectrophotometry with Zeeman background correction. No significant difference in Cd between CONT and LOCA was found except in femur, where it was increased. In CONT + Cd rats, peripheral tissues showed an increase in Cd of 30-71 fold above CONT rats. Brain regions exhibited a more modest 7-10 fold change, and serum Cd was 8.5 times above control. LOCA + Cd rats showed a 25-fold increase of Cd above LOCA in serum, 25-100 fold in peripheral tissues, and a 14-20 times in brain. These findings show that brain Cd is increased during Ca deficiency, but that central nervous system Cd changes less than peripheral tissue Cd. This increase in brain Cd could alter brain function. PMID- 1747759 TI - Melatonin modifies calmodulin cell levels in MDCK and N1E-115 cell lines and inhibits phosphodiesterase activity in vitro. AB - The interaction between melatonin and calmodulin was explored. Calmodulin cell levels in MDCK and N1E-115 cells cultured with 10(-9) M melatonin were increased after 3 days but decreased after 6 days. Melatonin inhibited calmodulin-dependent phosphodiesterase and when either melatonin or [3H]melatonin was preincubated with calmodulin and separated by electrophoresis, comigration of calmodulin with the radioactivity as well as modification of the Ca2+ calmodulin shift were observed. The results point out that one of the mechanisms of action of melatonin is a calmodulin-melatonin interaction. PMID- 1747760 TI - Effects of sciatic nerve transplants after fimbria-fornix lesion: examination of the role of nerve growth factor. AB - At two weeks post-transplantation, sciatic nerves inserted into the lesioned septo-hippocampal pathway contain NGF levels more than twice that of normal nerves. These transplanted nerves also contain regenerating cholinergic axons. Moreover, transplanted animals exhibit septal NGF levels that are significantly greater than in animals with lesions only. These results suggest a role for NGF in the ingrowth of axons into the transplants and in the increase in ChAT(+) septal neurons previously observed at this post-transplant time. PMID- 1747761 TI - Evidence that sensitivity to steroid anesthetics appears late in evolution. AB - The effects of pregnanolone, a steroid anesthetic, were compared with diethyl ether and short chain alkanols in 21 aquatic species from 7 phyla. Loss of righting reflex and escape response were used as indicators of anesthesia. All organisms were anesthetized by diethyl ether and short chain alkanols, but pregnanolone affected only organisms belonging to the phylum Chordata. It is probable that pregnanolone exerts its effect on the gamma-aminobutyric acid (GABA) receptor. Because many invertebrates do possess GABA receptors, our results suggest that a binding site at which steroid binding causes organismal anesthesia appeared early in chordate evolution on a previously existing GABA receptor. The results also appear to exclude a primary lipid bilayer site for steroid anesthetic action. PMID- 1747762 TI - Behavioral and anatomical consequences of unilateral fornix lesions and the administration of nimodipine. AB - Male Wistar rats subjected to unilateral fimbria-fornix transection by mechanical knife cut or to sham operations were tested in a water maze and in an open field. Half the animals in each group were treated with either 0.06 mg/kg nimodipine or vehicle, administered i.p. for 7 days, beginning the day of surgery. Animals were sacrificed and brains were processed for acetylcholine esterase (AChE) histochemistry. In the water maze, lesioned rats showed a significant impairment relative to the sham-operated animals. Nimodipine treatment did not improve performance. There were no differences among the groups in the observed frequencies of the open field behaviors of locomotion, hole-poke, rearing and grooming. A significant reduction of AChE-positive cell bodies was found in the medial septal region on the side of the lesion. There were no differences in water maze performance among groups of rats treated with 0.0, 0.5, 1.0, or 5.0 mg/kg nimodipine for 7 days, beginning the day of fimbria-fornix transection, in an attempt to determine any dose-dependent effect of the drug. PMID- 1747763 TI - Increased activity of superoxide dismutase in kindled brain and suppression of kindled seizure following intra-amygdaloid injection of superoxide dismutase in rats. AB - The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure. PMID- 1747764 TI - Cytokine-induced activation of the neuroendocrine stress axis persists in endotoxin-tolerant mice. AB - Chronic administration of lipopolysaccharide (LPS) to mice markedly reduced activation of the neuroendocrine stress axis elicited by an acute challenge dose of LPS. LPS-induced elevation in norepinephrine turnover in the hypothalamus showed complete tolerance whereas elevation of plasma corticosterone showed only partial tolerance. Challenge-induced increased turnover of dopamine in hypothalamus persisted in LPS-tolerant animals. Neuroendocrine activation persisted following acute challenge with interleukin-1 and tumor necrosis factor following chronic LPS exposure. PMID- 1747765 TI - Stimulation-induced setting of postural muscle tone in the decerebrate rat. AB - These studies demonstrate the presence of pontomedullary areas in the rat brainstem which, when stimulated electrically, serve to set postural muscle tone in the hindlimbs. Low amplitude stimulation of the dorsal tegmental field (DTF) was found to inhibit postural muscle tone and, in some rats, was found to decrease mean arterial pressure. Low amplitude stimulation of the ventral tegmental field (VTF) was found to increase postural muscle tone and, in all cases tested, was found to increase mean arterial pressure. PMID- 1747766 TI - Repeated injection of cocaine potentiates methamphetamine-induced toxicity to dopamine-containing neurons in rat striatum. AB - Rats were treated with daily injections of saline or cocaine (20 mg/kg i.p. x 15 days) and, beginning 24 h after the last injection, administered saline or methamphetamine (6.25-50 mg/kg s.c., BID x 4 days) and sacrificed two weeks later. Repeated daily administration of cocaine potentiated the long-lasting striatal dopamine depletions caused by methamphetamine. The results suggest that human use of cocaine may increase the likelihood of neurotoxicity resulting from ingestion of high doses of methamphetamine. PMID- 1747767 TI - Responses of neurons in the rat ventrolateral orbital cortex to phasic and tonic nociceptive stimulation. AB - Responses of ventrolateral orbital cortex (VLO) neurons to innocuous touch and pressure, and noxious pinch and cold were examined by extracellular recordings. Eight neurons increased their firing rate in a graded fashion to all stimuli applied, 4 units decreased their discharges, and 6 neurons remained unaffected. All responsive units displayed the greatest change in firing rate during noxious cold, and all exhibited whole-body receptive fields. These data further implicate the VLO in nonciception. PMID- 1747768 TI - Afferent influences on brainstem auditory nuclei of the chick: nucleus magnocellularis neuronal activity following cochlea removal. AB - Elimination of presynaptic elements often results in marked changes, such as atrophy and death, in postsynaptic neurons in the central nervous system. These transneuronal changes are particularly rapid and profound in young animals. In order to understand the cellular events underlying transneuronal regulation it is necessary to explore changes in the local environment of neurons following manipulations of their afferents. In previous investigations we have documented a variety of rapid and marked cellular changes in neurons of the cochlear nucleus of neonatal chicks (n. magnocellularis) following cochlea removal. In adult chickens, however, these transneuronal changes are either absent or minor. The goals of the studies presented here were to examine changes in the electrical activity of nucleus magnocellularis cells and their afferents following removal of the cochlea and to determine if these changes were similar in adult and neonatal animals. Two measures of electrical activity were used; multiunit recording with microelectrodes and incorporation of radiolabeled 2-deoxyglucose (2-DG). Microelectrode recordings revealed high levels of spontaneous activity in n. magnocellularis and n. laminaris, the binaural target of n. magnocellularis neurons. Neither puncturing of the tympanic membrane nor removal of the columella causes significant changes in spontaneous activity, although the latter results in a profound hearing loss (40-50 dB). Removal of the cochlea, on the other hand, results in immediate cessation of all extracellular electrical activity in the ipsilateral n. magnocellularis. Recordings from the same location for up to 6 h failed to reveal any return of spontaneous activity. When the electrode tip was placed in n. laminaris, unilateral cochlea removal had no discernible effect on extracellularly recorded spontaneous activity, probably due to the high levels of excitatory input from the intact ear. Bilateral cochlea removal, however, completely eliminated activity in n. laminaris. 2-DG studies conducted 1 h to 8 days following unilateral cochlea removal revealed marked decreases in 2-DG incorporation in the ipsilateral n. magnocellularis and bilaterally in the n. laminaris target of the ablated cochlea. No compensatory return of 2-DG incorporation was observed for up to 8 days. Comparisons of adult and neonatal chicks failed to reveal significant differences in the effects of cochlea removal on multiunit activity or 2-DG incorporation, suggesting that age differences in transneuronal regulation are due to intrinsic biochemical differences in young and adult neurons rather than differences in the proportion of synaptic input that has been abolished. PMID- 1747769 TI - Effects of tetrahydroaminoacridine (THA) on functional recovery after sequential lesion of the entorhinal cortex. AB - Unilateral lesions of rat entorhinal cortex produce a transitory performance deficit on spatial learning tasks, such as reinforced alternation in a T-maze. Tetrahydroaminoacridine (THA), a cholinesterase inhibitor, was administered to determine its effects on behavioral recovery using a reinforced alternation task in a T-maze. Rate of recovery after unilateral entorhinal lesion was not affected by a low dose of THA (0.05 mg/kg), while a higher dose (5.0 mg/kg) impaired recovery. Behavioral recovery was subsequently evaluated in the same rats following lesions to the contralateral entorhinal cortex. Serial bilateral lesions of the entorhinal cortex are known to produce a prolonged performance deficit on the alternation task. The 0.05 mg/kg THA group exhibited an intermediate rate of recovery, between the undamaged control group and bilateral lesion-saline injected groups. The group receiving 5.0 mg/kg of THA after bilateral lesion did not differ from the bilateral lesion-saline group. The failure of THA to significantly improve functional recovery in rats with lesions of the entorhinal cortex indicates that the compound may have limited applicability in treating human neurodegenerative disorders such as Alzheimer's disease. PMID- 1747770 TI - Time-dependent variations of central norepinephrine and dopamine following antigen administration. AB - Administration of sheep red blood cells (10(6) cells, i.p.) resulted in central norepinephrine (NE) and dopamine (DA) changes which corresponded with the time of the peak immune response. These amine variations, however, appeared to be specific to certain brain regions. The increased accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylethylene glycol, was evident in hypothalamus, locus coeruleus and hippocampus and a moderate reduction of NE was evident in the hypothalamus. Alterations of DA levels or utilization appeared in mesocorticolimbic structures (i.e. nucleus accumbens and prefrontal cortex) but not in striatum. This profile of transmitter changes was reminiscent of that previously shown to be induced by uncontrollable stressors and the possibility was offered that antigenic challenge is interpreted as a stressor by the central nervous system. PMID- 1747771 TI - Identification of the midbrain locomotor region and its relation to descending locomotor pathways in the Atlantic stingray, Dasyatis sabina. AB - The midbrain locomotor region (MLR) in the Atlantic stingray, Dasyatis sabina, was identified and characterized. Stimulation (50-100 microA, 60 Hz) of the midbrain in decerebrated, paralyzed animals was used to elicit locomotion monitored as alternating activity in nerves innervating an antagonist pair of elevator and depressor muscles. Effective sites for evoking locomotion in the midbrain included parts of several nuclei: the caudal portion of the interstitial nucleus of the medial longitudinal fasciculus and the caudomedial parts of the cuneiform and subcuneiform nuclei. This region did not include the red nucleus, any parts of the optic tectum or the medial or lateral mesencephalic nuclei. Electrical stimulation in the MLR evokes locomotion in either the ipsi- or contralateral pectoral fin, whereas stimulation in the medullary reticular formation evokes locomotion only in the contralateral fin. Lesion experiments were performed to identify the location of descending pathways from the midbrain to the medullary reticular formation. To abolish locomotion evoked by electrical stimulation in the MLR, the medial reticular formation in the rostral medulla had to be lesioned bilaterally, or the ipsilateral medial medullary reticular formation and fibers projecting from the MLR to the contralateral midbrain had to be disrupted. Injections of HRP into the magnocellular/gigantocellular reticular formation confirmed that this area received bilateral projections from the MLR. The MLR of the Atlantic stingray appears to be similar to the lateral component of the mammalian MLR and to the MLR in other non-mammalian vertebrates. PMID- 1747772 TI - The electrophysiological basis of epileptiform magnetic fields in neocortex: spontaneous ictal phenomena. AB - In a previous report (Barth, D.S. and Di, S., Brain Research, 530 (1990) 35-39), electrical measurements of epileptiform cellular currents produced by physiologically evoked interictal penicillin spikes in rat somatosensory cortex were directly compared to the extracranial magnetic fields these currents generate. The present study uses the same methodology to extend these observations to spontaneous interictal and ictal phenomena in rat auditory cortex, and provides a more realistic empirical foundation for physical models with which to interpret non-invasive neuromagnetic recordings of human focal seizures. These data indicate that seizure foci under 1 x 1 cm2 in cortical surface area are capable of producing magnetic fields that may be recorded at extracranial distances similar to those used in humans. Furthermore, physical models based on the dipole approximation appear to be appropriate for the interpretation of ictal magnetic field phenomena in neocortex. PMID- 1747773 TI - Designing a neural network simulator--the MENS modelling environment for network systems: I. AB - During recent years, the field of neural network research has increasingly attracted the interest of workers from a large number of different disciplines. Current research topics include aspects as different as detailed simulations in brain physiology, predictions of protein structure in biochemistry, database organization in computer science, or various technical applications. The common scheme behind these different approaches is the use of distributed networks of simple computational elements that communicate with each other by means of weighted links. Computer simulations of neural networks require an appropriate software environment. Due to the computational similarities of many classes of such networks, simulation software can be structured into modular components that, to a large degree, are independent of specific applications. The aim of this and the following paper is to discuss some of the design considerations concerning software for neural network simulations. The aspects presented are interesting for both the development of new simulation software and the efficient use and modification of existing programs. Therefore, the general user as well as the software designer may hopefully benefit from this material. This paper briefly introduces some of the basic principles of neural networks. After a short discussion of different approaches to software design, two simple example applications are presented in order to demonstrate a conceptual framework common to many network simulations. The transfer of these considerations to the design of simulation software is then shown by example of the MENS network simulator developed in the Max-Planck-Institute for Brain Research. The paper gives a general introduction to the layout of data structures and different software components. Using the two introductory examples some aspects of network analysis are demonstrated. The following paper then considers further details of the design of a neural network simulator with respect to performance, implementation, and testing. PMID- 1747774 TI - Designing a neural network simulator--the MENS modelling environment for network systems: II. AB - During recent years, neural network research has been extended to a large number of different fields, increasingly attracting the interest of workers from various disciplines. The computer simulations carried out with this research require an appropriate software environment. The computational similarities of many kinds of simulations allow the design of software components that are largely independent of the specific application. These considerations are reflected, for example, by the general layout of the MENS network simulator, as described in the accompanying first paper. This paper presents the design considerations for the simulator's different software components in more detail. In particular, design and implementation are discussed with respect to computational and memory efficiency. The discussion includes, for example, the representation of a network by the simulator's data structure, the file-driven configuration and initialization of a network, the simulator's stimulus and monitor system, and the simulator's control structures. In addition, the separation and interaction of application-specific and application-independent software components are addressed. Particular performance aspects comprise the implementation of synaptic delays, the dynamic deletion of synaptic links in network learning, and the preprocessing of stimulus films. In addition, some general aspects of simulator performance and testing are considered. The material presented in this paper concerns both the development of new simulation software and the efficient use of existing programs. Therefore, both the general user as well as the software designer may hopefully benefit from this presentation. PMID- 1747775 TI - Improved algorithms for searching restriction maps. AB - We present algorithms for searching a DNA restriction enzyme map for a region that best matches a shorter 'probe' map. Our algorithms utilize a new model of map alignments, and extensive experiments prove our model superior to earlier approaches for certain applications. Let M be the number of map sites and P be the number of probe sites. Our first algorithm, which optimizes only over a restricted class of alignments, requires O(MP log P) worst-case time and O(M + P) space. Our second algorithm, which optimizes over all alignments, runs in O(MP3) time and O(M + P2) space, under reasonable assumptions about the distribution of restriction enzyme cleavage sites. Combining the algorithms gives a map-searching method that optimizes over all alignments in O(MP log P) time in practice. The algorithms' effectiveness is illustrated by searches involving a genomic restriction map of Escherichia coli. PMID- 1747776 TI - A menu-shell for the GCG programs. AB - We provide a menu-driven integration of the genetic programs of the Genetics Computer Group (GCG). This allows in-experienced users a very simple access to all GCG programs regardless of the system environment. No modifications to the GCG package are necessary. PMID- 1747777 TI - Investigation of an expert systems approach to bacterial identification. AB - An investigation was carried out to assess the feasibility of using an expert systems approach to assist in the identification of unknown isolates of bacteria. A system was developed using Lisp which utilized the knowledge stored in standard bacteriological texts. A comparison of the expert systems approach and the probabilistic approach based on Bayes Theorem was made together with the advantages and disadvantages of each approach. PMID- 1747778 TI - Structural interpretation of fluorescence resonance-energy transfer measurements. AB - Fluorescence resonance-energy transfer (FRET) has been widely used to determine distance information in macromolecular systems. However, little has been written about methods for combining FRET distances into coherent structural models. I argue that the methods used so far are inappropriate. This paper describes an algorithm specifically tailored for finding structures from FRET measurements. This algorithm finds structures which fit the experimentally measured parameter, the efficiency of energy transfer, rather than derived distances. The algorithm was implemented in Mathematica and applied to FRET distances obtained for the contractile protein actin. The approach used is applicable to other experimental techniques which measure distances between a relatively small number of loci. PMID- 1747779 TI - A novel randomized iterative strategy for aligning multiple protein sequences. AB - The rigorous alignment of multiple protein sequences becomes impractical even with a modest number of sequences, since computer memory and time requirements increase as the product of the lengths of the sequences. We have devised a strategy to approach such an optimal alignment, which modifies the intensive computer storage and time requirements of dynamic programming. Our algorithm randomly divides a group of unaligned sequences into two subgroups, between which an optimal alignment is then obtained by a Needleman-Wunsch style of algorithm. Our algorithm uses a matrix with dimensions corresponding to the lengths of the two aligned sequence subgroups. The pairwise alignment process is repeated using different random divisions of the whole group into two subgroups. Compared with the rigorous approach of solving the n-dimensional lattice by dynamic programming, our iterative algorithm results in alignments that match or are close to the optimal solution, on a limited set of test problems. We have implemented this algorithm in a computer program that runs on the IBM PC class of machines, together with a user-friendly environment for interactively selecting sequences or groups of sequences to be aligned either simultaneously or progressively. PMID- 1747780 TI - Improving signal peptide prediction accuracy by simulated neural network. AB - The accuracy of distinguishing amino-terminal signal peptides from cytosolic proteins has been improved to 95% by combining a neural network classifier with von Heijne's statistical prediction, the latter is itself 85-90% reliable. The network processed not the cleavage site, but amino-terminal 20-residue segments by the 'tiling' algorithm. Concordant positive predictions of both methods led to the safe identification of 496 novel signal peptides from the Protein Identification Resources. PMID- 1747781 TI - A simple algorithm for averaging multiple cycles of waveforms having varying cycle periods. AB - We present a simple method for averaging multiple cycles of a waveform having cycles with varying periods. This averaging process preserves the morphology of the waveform by converting fixed time per point data into fixed fraction of cycle data. The algorithms are implemented using the ASYST system, which provides efficient code for performing the computations and permits straightforward integration of the data acquisition and analysis tasks. An example is given of the results of the program in processing cyclical waveforms obtained in respiratory research. PMID- 1747782 TI - A new method for finding long consensus patterns in nucleic acid sequences. AB - We describe a fast computer algorithm for identifying consensus patterns in DNA sequences. The method requires no prior assumptions about the consensus pattern other than its length. In particular no previous knowledge of the frequency or spacing of consensus patterns is required. However, a priori information about the shape of the consensus pattern, or invariability of individual positions, or the overall conservation level, can be utilized to enhance the selectivity and sensitivity of search. As the number of all possible consensus words increases very rapidly with length, comprehensive searches have usually been restricted to a maximum of 10-12 nucleotides, even when large mainframes are used. Our algorithm enables searching for consensus patterns of this order on current mid range and powerful microcomputers. Searches may be conducted on single, long sequences or a set of possibly aligned shorter sequences. We give examples of identified consensus patterns in both prokaryotic and eukaryotic DNA sequences, along with some typical program timings. PMID- 1747783 TI - A simple approach for the distribution of computationally intense tasks in an heterogeneous environment: distribution of the MDPP image-processing package. AB - A method has been developed to link the display ability of a high-resolution graphics workstation with the computational power of a local mainframe or a remote supercomputer via an electronic data network. The method allows this link to be established in a manner largely transparent to the user. The application of the method is illustrated by our successful distribution of the computationally intensive portions of an imaging program (MDPP) from a small VAX workstation to a VAX mainframe and Cray Y-MP8/832 using a simple message-passing technique. This technique can be applied to almost any configuration of networked machines. PMID- 1747784 TI - 'Size leap' algorithm: an efficient extraction of the longest common motifs from a molecular sequence set. Application to the DNA sequence reconstruction. AB - We propose a new method, called 'size leap' algorithm, of search for motifs of maximum size and common to two fragments at least. It allows the creation of a reduced database of motifs from a set of sequences whose size obeys the series of Fibonacci numbers. The convenience lies in the efficiency of the motif extraction. It can be applied in the establishment of overlap regions for DNA sequence reconstruction and multiple alignment of biological sequences. The method of complete DNA sequence reconstruction by extraction of the longest motifs ('anchor motifs') is presented as an application of the size leap algorithm. The details of a reconstruction from three sequenced fragments are given as an example. PMID- 1747785 TI - The application of SSADM to modelling the logical structure of proteins. AB - A logical design that describes the overall structure of proteins, together with a more detailed design describing secondary and some supersecondary structures, has been constructed using the computer-aided software engineering (CASE) tool, Auto-mate. Auto-mate embodies the philosophy of the Structured Systems Analysis and Design Method (SSADM) which enables the logical design of computer systems. Our design will facilitate the building of large information systems, such as databases and knowledgebases in the field of protein structure, by the derivation of system requirements from our logical model prior to producing the final physical system. In addition, the study has highlighted the ease of employing SSADM as a formalism in which to conduct the transferral of concepts from an expert into a design for a knowledge-based system that can be implemented on a computer (the knowledge-engineering exercise). It has been demonstrated how SSADM techniques may be extended for the purpose of modelling the constituent Prolog rules. This facilitates the integration of the logical system design model with the derived knowledge-based system. PMID- 1747786 TI - A Macintosh Hypercard stack to simulate the pharmacokinetics of infusion of intravenous anesthetic drugs (NarSim). PMID- 1747787 TI - PRIMEGEN, a tool for designing primers from multiple alignments. PMID- 1747788 TI - Automated protein sequence pattern handling and PROSITE searching. AB - The protein sequence searching program Scrutineer has been modified to search for targets from a file. We are distributing a reformatted file of PROSITES which can be read by Scrutineer. In addition, Scrutineer still accepts targets typed in interactively but can now write them out in the format required as input. Since the input format is the same as the output format, target management and re-use is simple. PMID- 1747789 TI - Psychosocial correlates of physician-patient communication at time of informed consent for bone marrow transplantation. AB - In obtaining informed consent for bone marrow transplantation (BMT) oncologist investigators may feel that they engender emotional distress in patients due to the disclosure of potentially lethal complications associated with BMT. However, little is known regarding the psychological profile of BMT patients at the time of informed consent or what impact the consent process has upon the physician patient relationship. The purpose of this study was to assess (1) the psychological symptom profile of patients consenting to BMT and (2) the relationship of behavioral and psychological factors to patients' perceptions of the quality of communication between physician and patient. The results indicated that adult BMT patients experienced significant psychological distress at the time at which they provided written consent for BMT. Two factors were positively related to perceived quality of communication between physician and patient: problem-focused coping style and perceived autonomy in decision making. These findings are interpreted in relation to the goals of informed consent and its implications for the physician-patient relationship. PMID- 1747790 TI - Pharmacokinetics of cis-diammine-dichlor-platin in a hemodialysis patient. AB - Cisplatin (CDDP) was administered to a 49-year-old dialysis female patient with advanced uterine cervical cancer. Analysis of the pharmacokinetics of CDDP in the patient with renal failure and at hemodialysis were compared with that of patients without renal impairment. CDDP at 30 mg was administered by drip infusion. The samples were ultrafiltrated and measured its concentration of both free (F-P) and total CDDP (T-P) by atomic absorption method. The effect of hemodialysis on the concentration of CDDP was analyzed. For the control, three patients without renal impairment were administered CDDP using the same method and its concentration was measured. The T-P clearance registered no difference between dialysis patients and controls, but F-P clearance in the HD patient was almost 5-fold lower than those in control patients, showing that F-P exposure to HD patients was 5-fold greater as a consequence of delayed disposition. The protein binding rate of CDDP was more gradual than that of the controls. The T-P and F-P removal rates positively correlated to the shunt side blood F-P. PMID- 1747791 TI - 5-Fluorouracil by protracted venous infusion: a review of recent clinical studies. AB - The pharmacokinetics of continuous infusion 5-fluorouracil make it an ideal drug to administer as a protracted infusion (continuous infusion more than 30 days). During the last decade numerous clinical studies have been conducted to evaluate the efficacy of 5-fluorouracil (5FU) administered as a protracted venous infusion. Phase II studies in metastatic colorectal cancer in 345 patients have demonstrated an average response rate of 36% (range 15-59%) and a prospective randomized study performed by the Mid-Atlantic Oncology Program (MAOP) has confirmed a higher response rate with 5FU infusion compared with a bolus schedule. Phase II studies in refractory carcinoma of the breast in 177 patients have demonstrated a 30% response rate (range 17-50%); studies in pancreatic, gastric, and refractory prostate cancer have also demonstrated clinical utility. The major toxicities of 5FU infusion are mucositis and hand-foot syndrome; life threatening myelosuppression is rare and treatment-related deaths have not been reported. 5FU infusion is a useful palliative treatment for many adult patients with advanced malignancies. PMID- 1747792 TI - Age, phenotype, and curability in acute myelogenous leukemia. PMID- 1747793 TI - Paying for expensive new technologies: Medicare's experiences with recombinant erythropoietin. PMID- 1747794 TI - In vitro evaluation of chemotherapeutic agents. PMID- 1747795 TI - Radionuclide detection of occult infection: current strategies. AB - A number of new radionuclide techniques are available for diagnosing infection. These include the radiolabeling of neutrophils and lymphocytes with a variety of chelating agents and isotopes, and the use of antibodies directed against bacteria in the inflammatory exudate. Other new techniques include radiolabeled nanocolloids, chemotactic peptides, and liposomes. This article reviews the evolving role of these techniques in the detection of sites of occult infection. PMID- 1747796 TI - Fraudulent research in science: the responsibility of the peer reviewer. PMID- 1747797 TI - Funding for cancer research. PMID- 1747798 TI - Cardiorespiratory alterations during normal pregnancy. AB - Maternal cardiorespiratory changes can hinder satisfactory evaluation of gravid women. Alterations in the maternal cardiorespiratory system may be further modified by pain, labor, surgery, maternal posture, and gestational age. Critical illness during pregnancy demands an aggressive multidisciplinary approach by health care professionals who are familiar with these changes. This article reviews pertinent issues that should assist physicians treating complex medical complications during pregnancy. PMID- 1747799 TI - Obstetric emergencies. PMID- 1747800 TI - Cardiac disease in pregnancy. AB - The pregnant patient with normal cardiac function can accommodate many significant alterations in the cardiovascular system without difficulty. Pregnancy in a patient with significant cardiac disease, however, can be extremely hazardous, resulting in decompensation and even death. these conditions account for up to 30% of maternal mortality. This article reviews the interaction between cardiac disease and pregnancy. PMID- 1747801 TI - Acute fatty liver of pregnancy. AB - AFLP is a syndrome that occurs in the last trimester or postpartum, characterized by jaundice, coagulopathy, and central nervous system disturbances. Renal insufficiency is common. Clinical and laboratory findings are nonspecific. Diagnosis is based primarily on histologic examination of the liver. The cause of AFLP is unknown. The illness has been associated with a high maternal and fetal mortality; with increased awareness and more liberal use of liver biopsy, however, milder forms of the disease are now recognized. Some speculate that AFLP is part of the spectrum of preeclampsia. Liver histology shows microvesicular fat and little or no inflammation or hepatocellular necrosis. Treatment consists of expeditious delivery and maximal supportive care, which may include intensive care unit monitoring, blood component therapy, glucose infusion, sodium restriction, diuretic agents, mechanical ventilation, and dialysis. The role of hepatic transplantation in AFLP appears limited. The risk of mortality during AFLP must be compared with the short- and long-term morbidity and mortality associated with liver transplantation. PMID- 1747802 TI - Clinical management of thromboembolic disorders in pregnancy. AB - Early diagnosis, treatment, and appropriate prophylaxis may prevent serious maternal sequelae of thromboembolism. Objective techniques for diagnosis should be used aggressively. Heparin is the preferred anticoagulant. Although the risks and benefits of prophylaxis are currently debated, it appears most prudent to consider subcutaneous heparin prophylaxis beginning in the first trimester. PMID- 1747803 TI - Management of severe preeclampsia and eclampsia. AB - Pregnancy-induced hypertension is a disorder of unknown etiology unique to pregnant women. Classic clinical manifestations include hypertension, proteinuria, and edema. Early recognition and proper management of this disease may serve to avoid serious maternal complications. Ultimate maternal treatment depends on delivery of the fetus and placenta. Advanced stages of this disease result in multi-organ system dysfunction that may be life-threatening to the mother and her fetus. Such maternal complications of PIH include severe hypertension, oliguria or anuria, HELLP syndrome, eclamptic seizures, liver rupture, pulmonary edema, cerebral edema, and abruptio placentae. A multidisciplinary approach of the critical care team often will effect a reduction in maternal morbidity and mortality. PMID- 1747804 TI - Intrapartum obstetric emergencies. AB - Shoulder dystocia, uterine inversion, and prolapse of the umbilical cord are three uncommon complications of the intrapartum period. These complications share several common characteristics in that they are rare, difficult to predict, and can result in significant morbidity and mortality. This article describes the etiology, predisposing factors, and methods of management of these complications. PMID- 1747805 TI - Abruptio placentae. AB - Despite our heightened awareness of placental abruption, this condition remains largely unpreventable. The incidence of placental abruption may actually be on the rise due to increasing use of cocaine and "crack" and a greater contribution from abdominal trauma. Whether recurrence of abruption associated with hypertension can be prevented with low-dose aspirin is yet to be determined. Unfortunately, although our recognition of this condition may have improved, placental abruption remains a high cause of perinatal morbidity and mortality. PMID- 1747806 TI - Amniotic fluid embolism. AB - Amniotic fluid embolism remains an enigmatic and often lethal condition. The pathophysiology is complex, however, from a clinical standpoint. Right or, more commonly, left heart failure is the dominant physiologic aberration. Disseminated intravascular coagulation is often present. The detection of squamous cells in the central circulation of living patients can no longer be considered pathognomonic for this condition. PMID- 1747807 TI - Postpartum hemorrhage. AB - Early PPH remains a significant cause of maternal morbidity and mortality. Many cases occur in women with antecedent risk factors and can thus be anticipated, promptly diagnosed, and promptly treated. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as ecbolic medications, uterine massage or bimanual compression, and blood and fluid replacement. Appropriate laboratory studies should be obtained promptly. Women with significant bleeding should receive blood product transfusions. Patients who do not promptly respond to these conservative measures should be considered and counseled for operative procedures. Surgical intervention, either to repair lacerations, transiently reduce pelvic pulse pressure, or remove the uterus, can be life-saving. PMID- 1747808 TI - Critical care obstetrics: management of the fetus. AB - Whenever a critically ill gravida presents for care, consideration should be given to consulting an obstetrician or a maternal-fetal medicine specialist. The technological advances of the past two decades permit these critical care obstetrical specialists to immediately assess fetal health with ultrasonography or a fetal monitor. By so doing, maternal and fetal care can be optimized through a team approach. PMID- 1747809 TI - Incentives and profit-sharing revisited. PMID- 1747810 TI - Cosmetic imaging: the new wave of co-diagnosis. PMID- 1747811 TI - Negotiating the road to financial success. PMID- 1747812 TI - Dr. Gordon Christensen at the CDA Convention. PMID- 1747813 TI - The future is now, seven steps for making it happen. AB - These seven key areas form a foundation on which a practice can build a solid structure to prepare for the future. In today's world, it is necessary for a dentist, as an employer, to become a risk taker. As the old saying goes "nothing ventured, nothing gained." Sometimes even the wrong move or action can be more positive than no action at all. Because of training and natural inclination, a majority of dentists are perfectionists, which can result in risk taking being a stressful aspect of management, growth and change. PMID- 1747814 TI - Dentistry for the future. PMID- 1747815 TI - Hepatitis & HIV: prevalence of infection and changing attitudes toward infection control procedures in British Columbia. AB - Dental professionals attending the annual meeting of the College of Dental Surgeons of British Columbia in June 1990 were involved in a survey to assess the prevalence of infection with Hepatitis B, Hepatitis C and Human Immunodeficiency viruses, the acceptance of vaccination for protection against Hepatitis B virus, and the compliance with infection control guidelines. Participation was voluntary and anonymous and required completion of a questionnaire and donation of a blood sample. Four hundred one of 1,995 convention attendees participated. Fourteen were found to have markers of Hepatitis B infection; 13 had antibodies to both Hepatitis B surface antigen and Hepatitis B core antigen, and one was positive for Hepatitis B surface antigen. One individual had markers for both Hepatitis C and Hepatitis B viruses. None tested positive for antibody to Human Immunodeficiency virus. Vaccination against Hepatitis B virus was reported overall by 67 percent of the participants, but dentists and hygienists had a higher rate of vaccination (82 percent and 81 percent, respectively) when compared to dental assistants (41 percent; P less than .001). Acceptance of infection control procedures was high, with 92 percent of participants reporting use of gloves for all patients and 82 percent reporting use of masks and eye protection. PMID- 1747816 TI - The issues of chemical dependency in dentistry. AB - The problem of chemical dependency is a topical issue in society today. With the increase in the number and types of prescription drugs, the proliferation of illegal drugs, and easy access to alcohol, chemical dependency has no socioeconomic boundaries. Professionals, blue collar workers and students, both male and female, are susceptible to the problem. The purpose of this paper is to review the literature on chemical dependency as it relates to the profession of dentistry. It will also look at the definition, prevalence, etiology, recognition, treatment and prevention of chemical dependency. Most of the evidence from the literature indicates that chemical dependency is a disease; it is treatable and can be prevented. The treatment of the disease requires the input of support groups at the professional level as well as at student level. The prevention of chemical dependency must begin in the curricula of dental schools with emphasis on the pharmacology and interaction of drugs. PMID- 1747817 TI - Utilization of dental services by older adults in four Ontario communities. AB - The elderly tend to use dental services less than most younger age groups. While the elderly's utilization rates may be rising, very low utilization by edentulous people depresses the overall rate for the group. We use data from the Ontario Study of the Oral Health of Older Adults to identify the variations in the use of dental services in the four study sites of Toronto, North York, Simcoe County and Sudbury and District. We reached 3,033 subjects by telephone and conducted dental examinations and a multi-item personal interview with 907 of them. The 907 subjects ranged in age from 50 to 87 years, 57 percent were female and two-thirds were born in Canada. Overall, 60.5 percent had seen a dentist or denturist in the previous year, but this was much lower among the edentulous (17 percent) when compared to the dentate (72 percent) (Chi-square test; p less than .0001). Of the 357 who did not visit a dentist or denturist in the previous year, nearly half (48 percent) felt they had nothing wrong and 20 percent reported they could not afford care. A high proportion (94 percent) of the edentulous reported visiting only for pain or trouble compared to 26 percent of the dentate (Chi-square test; p less than .0001). Using logistic regression, we found dental status (edentulous), community of residence (Sudbury), income (up to $20,000) and dental insurance coverage (none) were important factors in not making a dental visit in the last year. These same factors, plus education (elementary) were important where subjects reported visiting a dentist or denturist only when there was pain or trouble. PMID- 1747818 TI - Interactive videodisc: its place in today's nursing curricula. AB - The need for nurse educators to realistically assess interactive videodisc technology is readily apparent when one considers the analyzed educational benefits of that medium. Skills of discrimination, generalization, and sequencing are particularly targeted for the population of nursing students because these abilities are necessary for problem solving, analysis, nursing diagnosis, and conceptual learning. However, in these times of limited resources one must carefully evaluate the necessary expenditures versus the perceived advantages of the technology. This article reviews the literature on educational applications of videodisc technology and reports on a survey of videodisc use at 504 National League of Nursing (NLN) accredited baccalaureate programs. Results of this study validate the current cautious approach to implementing interactive videodisc technology in nursing programs. PMID- 1747819 TI - Computer conferencing: the "nurse" in the "Electronic School District". AB - As computer-based instructional technologies become increasingly available, they offer new mechanisms for health educators to provide health instruction. This article describes a pilot project in which nurses established a computer conference to provide health instruction to high school students participating in an electronic link of high schools. The article discusses computer conferencing, the "Electronic School District," the design of the nursing conference, and the role of the nurse in distributed health education. PMID- 1747820 TI - Application of a computer-based zero-one methodology to the assignment of nurses to a clinical rotation schedule. AB - This article discusses the application of a zero-one approach to the development of a total program schedule that assigns students to all required clinical courses in an academic nursing program. The approach is based on an operations research technique, zero-one programming. Unlike zero-one programming, the objective function in this formulation is arbitrary; any solution that meets the constraints of the system is acceptable. Also described in this article are the constraints that limit flexibility of student assignments (i.e., available clinical sites and units, instructors, day or evening, maximum class sizes, order of courses), a solution to the scheduling problem at Saint Joseph's (which involves 1,067 equations), and suggestions for the general utility of a zero-one approach for similar administrative problems. PMID- 1747821 TI - Computer graphics for slide presentations. AB - This applications article describes the use of a computer to generate high quality presentation materials. Different programs and methodologies are discussed. PMID- 1747822 TI - The use of machine learning program LERS-LB 2.5 in knowledge acquisition for expert system development in nursing. AB - LERS-LB (Learning from Examples using Rough Sets Lower Boundaries) is a computer program based on rough set theory for knowledge acquisition, which extracts patterns from real-world data in generating production rules for expert system development. From LERS-LB evaluation of an SPSS-X data file containing data for recovery room patients, it was concluded that both statistical data files and existing databases can be converted to decision-table format needed by LERS-LB, but it is less desirable to work with statistical files than a well-developed database. It was also concluded that choosing a well-developed database and checking it thoroughly for accuracy and completeness should be done before running LERS-LB, or other learning programs, to avoid problems with data errors. Using rough set theory and a technique called 'dropping conditions' LERS-LB offers, at least in theory, a possible method for identifying which data items are critical to nursing practice. Further research and continued LERS-LB program enhancements still may help with identifying critical data items versus redundant data for nursing practice. LERS-LB, and other learning programs, offer techniques which will help reduce the knowledge acquisition bottleneck in nursing expert system development. It is doubtful, however, that learning programs will eliminate the need for involving domain experts in evaluating rules and expert systems for clinical decision support. PMID- 1747823 TI - Polyethylene wear debris. PMID- 1747824 TI - Arthroscopic debridement of the knee. PMID- 1747825 TI - Cecal ulceration in a neutropenic child. PMID- 1747826 TI - Canadian Association of General Surgeons presidential address 1990. PMID- 1747827 TI - The future of vascular surgery in Canada. PMID- 1747828 TI - Choledochocholecystojejunostomy: a quick, effective method of biliary decompression for carcinoma of the pancreas. AB - The frequency of pancreatic carcinoma appears to be increasing. Effective treatment is essential for most patients whose tumours are unresectable. Definitive treatment by stenting techniques are currently limited to those patients who are high surgical risks, elderly, present with metastatic disease or refuse the surgical option. Surgical bypass offers the best palliation and should reliably decompress the biliary obstruction caused by the tumour with the least surgical trauma. Roux-en-Y choledochojejunostomy (CDJ), with or without a gastroenterostomy, is usually the preferred method of bypass; however, for patients with a distended gallbladder this procedure is often made easier by its removal. Even then providing a proximal, tension-free anastomosis can be challenging. In 13 consecutive patients who still had a gallbladder and required a biliary bypass for carcinoma of the pancreas, the authors interposed the gallbladder between the proximal bile ducts and a Roux-en-Y loop. This procedure could be done more quickly than CDJ and performed well. PMID- 1747829 TI - Antimicrobial prophylaxis in general surgery. AB - When used appropriately, antimicrobial prophylaxis is highly beneficial and cost effective. Antibiotics are not indicated for "clean procedures" such as hernia and breast surgery. A single preoperative dose will suffice, followed by an intraoperative dose if the operation takes more than 3 hours. For vascular (prosthesis or groin wound), head and neck (pharynx entered), thoracic (gastrointestinal or respiratory entrance) and high-risk gastroduodenal and biliary procedures, cefazolin, 1 g intravenously, is indicated. For procedures involving small intestine, appendix or penetrating abdominal trauma, cefoxitin or cefotetan, 2 g intravenously, is indicated. For colorectal procedures, either oral neomycin plus erythromycin or intravenous aminoglycoside plus clindamycin (or metronidazole) are effective. If valvular heart disease is present, endocarditis prophylaxis should be administered. PMID- 1747830 TI - Prophylaxis of deep venous thrombosis and pulmonary embolism. AB - Clinically silent deep venous thrombosis (DVT) develops in up to 25% of patients who undergo general surgical procedures. Approximately 10% of these thromboses are complicated by potentially fatal pulmonary embolism. Two recent meta-analyses of more than 70 published trials of DVT prophylaxis in general surgery have demonstrated conclusively that prophylaxis significantly reduces rates of DVT and fatal pulmonary embolism and results in improved overall survival. Physical methods of prophylaxis, including compression stockings and intermittent pneumatic compression, are as effective as pharmacologic prophylaxis (the most common regimen being heparin, 5000 units subcutaneously ever 8 to 12 hours). Bleeding complications are increased with the use of heparin, although they are clinically minor. Deep venous thrombosis prophylaxis should be routinely instituted for all general surgical patients who undergo major operative procedures. PMID- 1747831 TI - Prophylactic nutrition. AB - The potential clinical benefits of preoperative and postoperative enteral or parenteral nutritional support are reviewed. Special consideration is given to the problem of nutritional support for the cancer patient and to immunonutrition, a new research avenue in modular nutritional treatment. In the absence of uniformly accepted data regarding the use of prophylactic nutritional support, sound clinical judgement is still important. The simplest indications for the use of perioperative nutritional support are the following: patients without nutrition for 7 to 10 days; duration of illness anticipated to be longer than 10 days; malnutrition--more than 10% acute loss of usual body weight. PMID- 1747832 TI - Preventive measures in the elderly surgical patient. AB - The death rates associated with all forms of surgical illness increase consistently with age but appear more closely related to physiologic and medical status than to age per se. Changes in physiologic function with advancing age are marked by a decreased sensitivity to perturbations and a decreased efficiency of homeostatic mechanisms. Recognition of the heterogeneity of the aging process is fundamental to appropriate decision-making in the elderly surgical patient and thus to avoiding complications. Careful preoperative assessment of medical problems and potential age-related changes in physiologic function, preoperative orientation and teaching, consideration of deep venous thrombosis prophylaxis, effective pain management, early postoperative mobilization and careful attention to drug and fluid and electrolyte therapy are essential in management of the elderly surgical patient. PMID- 1747833 TI - The surgical stress response: should it be prevented? AB - Postoperative complications such as myocardial infarction, pulmonary infection, thromboembolism and fatigue are probably related to increased demands, hypermetabolism, catabolism and other physiologic changes included in the global "surgical stress response." Strategies have been developed to suppress the detrimental components of the stress response so as to improve postoperative outcome. Of the various techniques to reduce the surgical stress response, afferent neural blockade with regional anesthesia to relieve pain is the most effective, although not optimal. Data from numerous controlled clinical trials have demonstrated a reduction in various aspects of postoperative morbidity by such a nociceptive blockade. Although a causal relationship has still to be demonstrated, these findings strongly argue the concept of "stress-free anesthesia and surgery" as an important instrument in improving surgical outcome. PMID- 1747834 TI - Noninvasive assessment of cardiac transplant rejection. A critical look at the approach to acute rejection. AB - The diagnosis of acute rejection remains a key issue in the management of the heart transplant recipient. Myocardial biopsy for tissue examination is the basic step for screening and diagnosis of acute rejection. Although endomyocardial biopsy is reliable, it is an inefficient approach to screening after transplantation and yielded only a 14% rate of positive results in the author's experience, from 1983 to 1990, of 568 biopsies. A reliable noninvasive method for screening acute rejection is therefore needed. Numerous noninvasive methods have been studied to monitor the systemic immune process against the allograft or to evaluate the effect of rejection on graft function and status. For 13 methods of evaluating immune process against the allograft the sensitivity and specificity ranged from 13% to 95% and 19% to 94% respectively. For nine methods of evaluating allograft function, sensitivity and specificity ranged from 60% to 93% and 65% to 97% respectively. Overall, methods monitoring allograft function and status have better results in predicting acute rejection. Nevertheless, the author estimated that 15 episodes of acute rejection would have been missed by these monitoring methods in his group of patients. PMID- 1747835 TI - [Pediatric heart transplantation 1990]. AB - In this presentation the author updates the progress made in pediatric cardiac transplantation through a review of the results obtained at Ste-Justine Hospital (SJH) and of the recent literature. Of 56 children referred to SJH for cardiac transplantation, 27 met the selection criteria; 10 died before receiving a new heart and 2 are still awaiting transplantation. Fifteen children, aged 3 to 16 years, have received a transplant. Ten of them had 32 birth defects, all of which were repaired at the time of transplantation thanks to improved graft removal methods and innovative surgical techniques. This study demonstrates that birth defects are not a contraindication to cardiac transplantation in children. Triple drug immunosuppression was used, and the cyclosporine blood levels were maintained in the range of 100 to 200 ng/mL. Survival at 2 years was 78%. Episodes of acute rejection occurred at a rate of 0.5 per patient, 85% of them within the first 3 months after transplantation. Adequate renal function was preserved (creatinine clearance between 89 and 102 mL/min.m-2). The use of low dose cyclosporine might explain in part the lack of significant nephrotoxicity. Reversible high blood pressure was observed in 5 of 13 patients during the first 6 months postoperatively. Multifactorial analysis identified, as a likely cause, a higher dose of steroids and cyclosporine during this period. Annual coronary angiography did not reveal any lesion, and apart from the acute rejection episodes, cardiac function was normal at rest, and the transplanted children have maintained an excellent level of activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1747836 TI - Mechanical bridge to cardiac transplant: where do we stand in 1990? AB - Various mechanical devices have been used to support the circulation in patients requiring cardiac transplantation who are in cardiogenic shock. The devices produce either a pulsatile or nonpulsatile blood-flow pattern. Of the former, the intra-aortic balloon pump is the most frequently used. However, it augments but does not replace the function of the left ventricle. At the Ottawa Heart Institute, orthotopic replacement of both ventricles with a total artificial heart has proven a reliable and effective bridge to transplantation in selected patients. Heterotopic ventricles, known as ventricular assist devices, may also be used to replace the function of one or both ventricles and are increasingly being used to maintain the circulation. The future of nonpulsatile devices for mechanical support remains unclear because the long-term effects of this unphysiologic flow pattern are unknown. As refinements in circulatory support devices continue and as patient selection and timing of device insertion become more clearly defined, the results in these patients will likely approach those of elective cardiac transplantation. PMID- 1747837 TI - Management of fistula-in-ano: 1990 Roussel Lecture. AB - Fistulas-in-ano may be classified as simple or complex, or according to their anatomy--intersphincteric, transsphincteric suprasphincteric or extrasphincteric. Most of them are treated surgically. Simple fistulas may be treated by fistulotomy, but complex or high fistulas require careful evaluation and often require alternative surgical procedures. In all instances, the objective should be to eradicate the fistula without compromising continence. Perianal disease may be present in 10% to 80% of patients with Crohn's disease. In these patients treatment must be individualized. Important considerations are the presence or absence of rectal disease, the complexity of the fistula and the strength of the anal sphincter muscle. Treatment options include fistulotomy, simple drainage or unroofing of abscesses and fistulas, use of medical agents, bowel rest, construction of a loop ileostomy and, ultimately, proctectomy. PMID- 1747838 TI - Value of urologic investigation in a targeted group of women with recurrent urinary tract infections. AB - According to the conclusions of clinical studies, excretory urography and cystoscopy are of no value in managing the majority of women who have a history of recurrent urinary tract infection (UTI). Of 475 women with recurrent UTIs, 186 were prospectively targeted for evaluation by cystoscopy and ultrasonography or excretory urography from selection criteria based on the degree of complicating factors, to determine the value of urologic investigation. Thirty-nine patients had significant detectable abnormalities, and 20 of them required surgical intervention. Definite indications for urologic evaluation include hematuria (gross hematuria and persistent microscopic hematuria between infections), pyelonephritis and a presentation that is not typical for simple uncomplicated UTIs (obstructive symptoms, infection with urea-splitting bacteria, clinical impression of persistent infection or urinary calculi). Diabetes itself does not warrant urologic evaluation. The findings from this study suggest that cystoscopy and upper urinary tract evaluation do play a role in the management of a selected group of women with UTIs. PMID- 1747839 TI - Arthroscopic debridement of the knee for osteoarthrosis. AB - To evaluate outcome after arthroscopic debridement, the records of 171 patients with osteoarthrosis of the knee were reviewed. All patients were unresponsive to conservative management and were treated arthroscopically. Procedures included lavage, meniscectomy, chondrectomy, removal of free bodies and removal of limited osteophytes. Outcome assessment was retrospective, evaluating the need for further surgery, control of pain, improved function and patient satisfaction. Sixty-five percent of patients felt their symptoms were improved. There was excellent control of pain in 38% and improved function in 22%. Subsequent surgical procedures were required in 12% at an average follow-up of 25 months. No factors were identified that correlated with the outcome, including the extent of degenerative changes and of debridement and patient profile. Arthroscopic debridement is a temporizing procedure with good patient satisfaction. Marked, but unpredictable, improvement in symptoms is seen in one patient out of three. PMID- 1747840 TI - Aseptic loosening in total hip implants: the role of polyethylene wear debris. AB - Radiologic and routine histologic examinations, transmission electron microscopy and scanning electron microscopy were carried out on membranes retrieved from the following hip implant prostheses: loose cemented metal-on-polyethylene, resorptive cysts around fixed cemented metal-on-polyethylene, cemented without polyethylene (Thompson), noncemented without polyethylene (Moore), loose ceramic on-ceramic and loose noncemented metal-on-polyethylene. From histologic analysis the most common factor in the membranes reviewed, in terms of production of multinucleated giant cells, is the presence of polyethylene wear debris. Neither loosening of the implant nor the presence or absence of bone cement produces such cells within the membrane. PMID- 1747841 TI - [A utilization review program of cefoxitin]. AB - A drug utilization review program of cefoxitin was conducted in a 714-bed teaching hospital. Health records of all 43 in-patients who received cefoxitin during the month of November 1987 were reviewed retrospectively. The use of cefoxitin (47 courses) was evaluated on the basis of "appropriate use" criteria developed from the literature and the physician's clinical experience. Of the 47 courses evaluated, cefoxitin was prescribed for prophylaxis in 47%, and its use was considered inappropriate in 86% of these. Overall, 66% of total cefoxitin usage was deemed inappropriate in this hospital. The cost associated with inappropriate use was estimated at $2672 for the period of the study. Corrective measures were then implemented to rectify the identified problems. A second study was conducted 2 years later to assess the impact of the corrective measures. This utilization review program of cefoxitin showed that optimal use of a drug requires not only close collaboration between pharmacists and physicians but a continuous and not a sporadic process of surveillance of the prescription for the drug being studied. PMID- 1747842 TI - Cervical esophageal diverticulum associated with an impacted denture: a case report. AB - The authors describe the case of a 19-year-old man who had swallowed his three toothed radiolucent upper denture 2 years before the current admission. Although radiologic examination of the soft tissues of the neck and the results of barium meal examination were reported as normal immediately after the event, a barium meal examination 2 years later revealed formation of a cervical esophageal pouch, within which the denture was found at operation. The swallowing and possible impaction of a foreign body within the esophagus should prompt upper gastrointestinal endoscopy despite a negative result of a barium meal examination. Endoscopic removal is the treatment of choice, but surgery is appropriate in selected cases. PMID- 1747843 TI - Osteomyelitis of the pelvis due to Fusobacterium nucleatum. AB - Anaerobic pelvic osteomyelitis occurs rarely in children. A case of Fusobacterium nucleatum osteomyelitis of the right ilium [correction of ileum] in a child without apparent risk factors is described. This case emphasizes the value of diagnostic aspirates. Therapy with a combination of intravenous and oral clindamycin led to successful resolution of the infection. PMID- 1747844 TI - Internal jugular vein reconstruction using a superficial femoral vein graft. AB - Numerous methods of venous reconstruction have been described to help prevent the many complications related to bilateral ligation of the internal jugular veins. The authors report a case in which the superficial femoral vein was used as the donor graft for reconstruction of the internal jugular vein in a 61-year-old man who underwent a tonsillar commando procedure for cancer. The advantages of using this donor vein for reconstruction of the internal jugular vein are summarized. PMID- 1747845 TI - Failure of a titanium endoprosthesis--a case report. AB - A titanium-head Thomson endoprosthesis was revised 2.5 years after insertion. Metallosis with burnishing of the head and acetabular erosion were noted. The stem and the cement mantle were in perfect condition. Because this is not an isolated case, the author recommends that a titanium-stem endoprosthesis have a cobalt-chrome or ceramic bearing surface. PMID- 1747846 TI - Overview of new dermatopathology techniques. PMID- 1747847 TI - Gene rearrangement analysis in lymphoid neoplasia. AB - Current uses for gene rearrangement analysis in clinical dermatology are listed in Table 3. This technique is useful for determining the existence of clonal populations within a background of polyclonal lymphoid cells; therefore, it is helpful in the diagnosis and staging of patients with CTCL and PTCL. Although dual genotypes do occur, this technique is usually capable of determining lineage in a clonal lymphoid infiltrate and elucidating and characterizing the etiopathogenesis of certain neoplasms. On the basis of this review of the literature and our own experience, we conclude that gene rearrangement analysis shows great promise for monitoring response to therapy and detecting progression or relapse in patients with CTCL and PTCL. With the recent technology of PCR, it is possible to amplify specific sequences of DNA, detect molecular alterations in individual malignant T cells, and even identify exogenous retroviral gene sequences in tissues of patients with CTCL. Although gene rearrangement analysis has supported or established the clonal nature of lymphomatoid papulosis, pre Sezary syndrome, granulomatous slack skin syndrome, and follicular mucinosis, the clinical significance of these findings is not yet clear. In the case of primary cutaneous B-cell lymphoma and its benign counterpart, B-cell pseudolymphoma, further investigation will be needed to determine the clinical significance of clonal rearrangements. PMID- 1747848 TI - In situ hybridization. PMID- 1747849 TI - The polymerase chain reaction. AB - In a short time the PCR techniques has revolutionized research technology in many areas of medicine. Because of the ease and rapidity of the technique it is quickly becoming a standard clinical test for many diseases. Clinical applications continue to emerge from research labs and should rapidly expand to facilitate rapid medical diagnosis. PMID- 1747850 TI - Diagnosis with oligonucleotides. PMID- 1747851 TI - Flow cytometry in the evaluation of dermatology patients. PMID- 1747852 TI - Analysis of cutaneous foreign bodies. AB - Foreign materials from exogenous sources pose a constant challenge to the diagnostic skills of practicing dermatologists. Depending upon circumstances, radiologic, histologic, and ultrastructural techniques can be of assistance in ascertaining the presence and nature of the substance in question. With technologic advancements, identification of small-sized particles is no longer limited to morphologic study alone. Ultrastructural analytic techniques now permit identification of minute particles or quantities of material in tissues with relative ease. No doubt, further application of currently available and newly evolving analytic systems will expand our limits of detection and enhance our scientific knowledge. PMID- 1747853 TI - Immunoelectron microscopy and immunofluorescence antigenic mapping: diagnostic applications. AB - In selected situations, direct and indirect IEM may provide important diagnostic information for the clinician, as pertains to the diagnosis and therefore prognosis in a given patient. As discussed, however, all of the more conventional approaches should be pursued before consideration is given to the performance of IEM, knowing its relative cost and technical difficulty. In contrast, we consider immunofluorescence antigenic mapping to be the diagnostic method of choice for the determination of the type of inherited EB present in affected individuals. When additional ultrastructural or morphometric data is required, then TEM can be performed as an adjunct study once it is determined by mapping technique that additional useful information may be derived. PMID- 1747854 TI - Ultrastructural morphometry in the diagnosis of mycosis fungoides and Sezary's syndrome. PMID- 1747855 TI - New ways to demonstrate pathogenic organisms. PMID- 1747856 TI - Immunohistochemistry in the diagnosis of malignant melanoma. PMID- 1747857 TI - Immunohistochemical evaluation of vascular neoplasms. AB - Immunohistochemistry is of proven value in the evaluation of cutaneous vascular neoplasms. Nonetheless, the lack of sensitivity and specificity demonstrated by some endothelial markers requires that a panel of antibodies to other lineage related determinants be applied in this context. Compared with electron microscopy, enzyme-linked antibody techniques can be applied in a cost-effective manner, with a satisfactory diagnostic result in most cases. The efficacy of these methods will likely improve as more sensitive and specific markers of endothelial differentiation are characterized. For the time being, the exclusion of non-endothelial proliferations remains an important aspect of the differential diagnosis of vascular tumors. PMID- 1747858 TI - Recent advances in the study of the taxonomy, pathogenicity, and infectious syndromes associated with the genus Aeromonas. AB - Over the past decade, the emergence of Aeromonas species as bona fide human pathogens and their probable role as etiologic agents of bacterial gastroenteritis have resulted in an explosion of scientific interest in the genus. Major accomplishments occurring in this field during that interval include a more refined taxonomy, identification of new cell-associated factors (surface layers, pili), and the molecular analysis of selected extracellular gene products that may play a critical role in pathogenesis (hemolysins, enterotoxins). This review provides an updated overview of recent systematic, clinical, and pathophysiologic advances and defines key areas of medical and scientific interest in which major questions remain unanswered. PMID- 1747859 TI - Histoplasma variation and adaptive strategies for parasitism: new perspectives on histoplasmosis. AB - This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease syndromes can be explained in part by natural variations within the fungal population and adaptations made by individual organisms to specific environments. H. capsulatum grows as mycelia and conidia in the soil; once inhaled, the organism undergoes a dramatic morphological and physiological conversion to a yeast form. The yeasts proliferate within the phagolysosomes of macrophages, using a variety of specific strategies for intracellular survival. Even avirulent strains or variants are able to avoid being killed by macrophages and instead establish inapparent or persistent infections. The ingested avirulent organisms assume enlarged shapes similar in appearance to those seen in histological sections of tissues from patients with histoplasmosis. Respiratory tract epithelial cells also appear to play a role in persistence: within them yeasts undergo phenotypic switching akin to the phase variation observed in other pathogens. This particular change involves the loss or modification of cell wall alpha-(1,3)-glucan, which is also correlated with the spontaneous appearance of avirulent variants. The repertoire of adaptive responses and natural variations within this species probably evolved from the need to adjust to a wide range of dynamic environments. In combination with the immune status of the host, these characteristics of H. capsulatum appear to influence the epidemiology, extent, and persistence of histoplasmosis. PMID- 1747860 TI - Applications of cellular fatty acid analysis. AB - More than ever, new technology is having an impact on the tools of clinical microbiologists. The analysis of cellular fatty acids by gas-liquid chromatography (GLC) has become markedly more practical with the advent of the fused-silica capillary column, computer-controlled chromatography and data analysis, simplified sample preparation, and a commercially available GLC system dedicated to microbiological applications. Experience with applications in diagnostic microbiology ranges from substantial success in work with mycobacteria, legionellae, and nonfermentative gram-negative bacilli to minimal involvement with fungi and other nonbacterial agents. GLC is a good alternative to other means for the identification of mycobacteria or legionellae because it is rapid, specific, and independent of other specialized testing, e.g., DNA hybridization. Nonfermenters show features in their cellular fatty acid content that are useful in identifying species and, in some cases, subspecies. Less frequently encountered nonfermenters, including those belonging to unclassified groups, can ideally be characterized by GLC. Information is just beginning to materialize on the usefulness of cellular fatty acids for the identification of gram-positive bacteria and anaerobes, despite the traditional role of GLC in detecting metabolic products as an aid to identification of anaerobes. When species identification of coagulase-negative staphylococci is called for, GLC may offer an alternative to biochemical testing. Methods for direct analysis of clinical material have been developed, but in practical and economic terms they are not yet ready for use in the clinical laboratory. Direct analysis holds promise for detecting markers of infection due to an uncultivable agent or in clinical specimens that presently require cultures and prolonged incubation to yield an etiologic agent. PMID- 1747861 TI - Immunodiagnosis of aspergillosis. AB - Aspergillus species are ubiquitous fungi and have been implicated as the causative agents of a variety of lung disorders in humans. These disorders include allergic, saprophytic, and systemic manifestations. The allergic disorders mainly affect atopic persons, and invasive or systemic diseases affect immunosuppressed individuals. Immunodiagnosis can help the practitioner diagnose these diseases. Demonstration of circulating antibodies is a useful criterion, but the lack of dependable and standardized antigens is a limiting factor in the diagnosis of most Aspergillus-induced diseases. Despite this limitation, however, immunodiffusion and enzyme-linked immunosorbent assays have been widely used for the detection of antibodies in the sera of patients with aspergillosis. Similarly, crude and semipurified antigens are being used to demonstrate skin hypersensitivity in patients, and several methods have been useful in the detection of antigenemia in patients with invasive aspergillosis. With a growing number of reports on the incidence of aspergillosis and an increase in the number of immunosuppressed individuals in the population, more rapid methods and more reliable reagents for immunodiagnosis are needed. With recent attempts at obtaining reliable reagents for through hybridoma technology and molecular biological techniques, substantial progress toward efficient immunodiagnosis may be achieved. PMID- 1747862 TI - Serodiagnosis of parasitic diseases. AB - In this review on serodiagnosis of parasitic diseases, antibody detection, antigen detection, use of monoclonal antibodies in parasitic serodiagnosis, molecular biological technology, and skin tests are discussed. The focus at the Centers for Disease Control on developing improved antigens, a truly quantitative FAST-enzyme-linked immunosorbent assay, and the very specific immunoblot assays for antibody detection is highlighted. The last two assays are suitable for field studies. Identification of patient response in terms of immunoglobulin class or immunoglobulin G subclass isotypes or both is discussed. Immunoglobulin isotypes may asist in defining the stage of some diseases. In other instances, use of a particular anti-isotype conjugate may increase the specificity of the assay. Monoclonal antibodies have played important roles in antigen purification and identification, in competitive antibody assays with increased sensitivity and specificity, and in assays for antigen detection in serum, body fluids, or excreta. Molecular biological technology has allowed significant advances in the production of defined parasitic serodiagnostic antigens. PMID- 1747863 TI - Susceptibility testing of anaerobic bacteria: myth, magic, or method? AB - The demand for susceptibility testing of anaerobes has increased, yet consensus as to procedure and interpretation in this area has not been achieved. While routine testing of anaerobic isolates is not needed, certain isolates in specific clinical settings should be tested. Also, laboratories may monitor their local antibiograms by doing periodic surveillance batch testing. The National Committee for Clinical Laboratory Standards has published a protocol of methods approved for susceptibility testing of anaerobic bacteria. Both agar and broth microdilution are included; however, the broth disk elution method is no longer approved by the National Committee for Clinical Laboratory Standards because of method-related interpretive errors. A number of newer methods are undergoing evaluation and seem promising. Clinicians and microbiologists reviewing susceptibility reports should be aware of sources of variability in the test results. Variables in susceptibility testing of anaerobes include the media and methods used, organisms chosen for testing, breakpoints chosen for interpretation, antibiotic, and determination of endpoint. Clustering of MICs around the breakpoint may lead to significant variability in test results. Adherence of testing laboratories to approved methods and careful descriptions of the method and the breakpoints used for interpretation would facilitate interlaboratory comparisons and allow problems of emerging resistance to be noted. A variety of resistance mechanisms occurs in anaerobic bacteria, including the production of beta-lactamase and other drug-inactivating enzymes, alteration of target proteins, and inability of the drug to penetrate the bacterial wall. Antimicrobial resistance patterns in the United States and abroad are described. PMID- 1747865 TI - Genetic abnormalities in myelodysplastic syndrome. PMID- 1747866 TI - Alu family variations in neoplasia. AB - Human chromosomes contain about one million copies of dispersed repeats of the Alu family which are distributed non-randomly. In this study we have compared the pattern of hybridization of tritiated Alu-probes on chromosomes of PHA-stimulated lymphocytes of normal donors and of non-stimulated bone marrow cells of acute leukemia patients, and found regular differences in this pattern over some chromosome bands (3q26, 8p11-p12, 14q24, 15q21, 6q22) between normal individuals and leukemia patients. These data were interpreted as indicative of somatic variation of the Alu family in acute leukemia. Possible mechanisms of the variation and the role of the Alu family in chromosome rearrangements in neoplasia are discussed. PMID- 1747864 TI - Bacterial vaginosis. AB - Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed. PMID- 1747867 TI - Establishment of a rhabdoid tumor cell line with a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23). AB - The malignant rhabdoid tumor is a rare, poorly understood tumor which occurs primarily in children. The kidney is a frequent primary site of origin, but the tumor has arisen in other mesodermally derived tissues as well. Controversy exists regarding the embryonic origin of the rhabdoid tumor and recent histopathologic studies suggest that it may be of neuroepithelial origin. Our immunohistochemical and electron micrographic studies support this theory. No consistent chromosome abnormalities have been reported in this tumor and no cell lines are available for study. We have established and characterized the first rhabdoid tumor cell line. It possesses a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23). The translocation may provide an important clue to the pathogenesis of the tumor as well as an opportunity for further study of the involved chromosome regions. PMID- 1747868 TI - Trisomy 13 as a primary chromosome aberration in acute leukemia. AB - Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia. PMID- 1747869 TI - Loss of amplification and appearance of a novel translocation site of the c-myc oncogene in HL-60 leukemia cells. AB - The chromosomal localization of c-myc sequences was determined by in situ hybridization in HL-60 cells (HL-60a) which contain an amplified c-myc locus and in an HL-60 subline (T-HL60) which has lost the amplification and has proportionately lower levels of c-myc RNA. While in HL-60a cells amplified c-myc sequences were found on the M3q+ marker chromosome, in T-HL60 cells one or few residual c-myc copies were found on a novel 4q+ marker chromosome. Comparative phenotypic analysis of HL-60a and T-HL60 cells show that the decrease in c-myc amplification/expression is not accompanied by changes in the malignant phenotype, namely in doubling time and clonogenic capability in semi-solid media. The significance of these results is discussed in the context of the role of c myc amplification in the establishment and/or maintenance of the leukemic phenotype in HL-60 cells. In general, these results further underscore the utility of in situ hybridization analysis in identifying oncogene translocations which are not detectable by conventional karyotypic analysis. PMID- 1747870 TI - Unstable chromosome aberrations in bladder and renal cell carcinoma. AB - Structural chromosome aberrations were investigated in 18 bladder carcinoma and 14 renal cell carcinoma patients. Unstable chromosome aberrations, such as breaks, gaps, minutes, and fragments, appeared in varying proportion. Double minutes (dmin) were also observed. In bladder carcinoma, 10 kinds of aberration were observed in 38.8% of the metaphase analyzed, and, in renal cell carcinoma, 7 kinds of aberrations were observed in 15.0%. The frequency of chromosome aberrations observed, and the occurrence of dmin and of aneuploidy, were correlated positively with histopathological grade and stage. From the results obtained here, we conclude that study of chromosome aberrations should be added as one of investigations for evaluating the malignant potential of the tumors. PMID- 1747871 TI - Translocation (Y;2) in childhood acute lymphoblastic leukemia. AB - A case of ALL in a 2 1/2-year-old boy with fatal outcome is presented. Cytogenetic analysis revealed a hypodiploid karyotype: 45,X-Y,-2,+der (2)t(Y;2), 12,i(17q),+mar. Some metaphases represented a sideline with 44 chromosomes and monosomy 8 was a consistent anomaly. These findings are rather uncommon in ALL. Hypodiploidy and the translocation, however, indicated poor prognosis in this case. PMID- 1747872 TI - Cytogenetic variability and kinetochore proteins. Comparison among populations derived from single-cell cultures. AB - This study reports comparative changes in five sub-lines obtained from a transformed culture of rat cerebral origin. Two of the lines were obtained from the original cell population while three others were raised from single-cell cultures. The comparative study was carried out on the DNA content and several cytogenetic parameters including variability in chromosome number, anaphase bridges, acentric fragments, chromosomes without detectable kinetochore proteins, and the frequency of micronuclei in these five lines. All cell lines, including the single-cell-derived clones expressed considerable variability in all aspects. One interesting aspect is the evolution of a chromosome with compound centromere, which is present only in two cell lines. The data indicate that the clone derived from a single cell does not maintain uniformity and even single cells have some sort of inherent potential to generate extreme variability. Some numerical variability may be attributed to a new phenomenon of a lack of kinetochore proteins seen on some chromosomes. PMID- 1747873 TI - Cytogenetic study of acoustic neuroma. PMID- 1747874 TI - Acute effects of amiodarone on ultrastructure and electrical activity of isolated guinea pig hearts. AB - STUDY OBJECTIVE: The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts. DESIGN: Group 1: The influence of 10 microM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. EXPERIMENTAL PREPARATIONS: Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span. MEASUREMENTS AND MAIN RESULTS: A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p less than 0.01% +47(12)%, p less than 0.01, respectively] and on heart rate [-30(9)%, p less than 0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p less than 0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 microM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol.g-1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema. CONCLUSIONS: These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium. PMID- 1747875 TI - Absence of xanthine oxidoreductase activity in human myocardium. AB - STUDY OBJECTIVE: The aim was to examine whether or not xanthine oxidase activity may be a significant source of oxygen derived free radicals in the human heart. DESIGN: Xanthine oxidoreductase activity of human myocardium was assayed in vitro. In addition, tests were performed to assess whether or not endogenous inhibitors of the enzyme were present in myocardial homogenates. The enzyme assay was based on high performance liquid chromatography with electrochemical and/or radiochemical detection of hypoxanthine, xanthine, and urate. SUBJECTS: Measurements were done on (a) isolated perfused rat myocardia and (b) left ventricular needle biopsies and papillary muscles obtained during elective cardiac surgery (chiefly aortic and/or mitral valve replacement and aortocoronary bypass) (n = 105 patients). MEASUREMENTS AND MAIN RESULTS: Homogenisation of human papillary muscles in buffer caused significant accumulation of hypoxanthine but not xanthine or urate. In addition, during incubation of crude myocardial homogenates with exogenous xanthine or hypoxanthine in the presence of NAD+ and/or O2 no production of urate was detected. Likewise, following aerobic incubation of papillary muscle homogenates with 14C-hypoxanthine neither 14C xanthine nor 14C-urate were formed. Absence of xanthine oxidising activity was also observed with human papillary muscle extracts that were subjected to either ultrafiltration or gel filtration. In contrast, the rat heart was found to contain abundant xanthine oxidoreductase activity. The rat heart enzyme was inhibited by both allopurinol and oxypurinol but remained active when mixed with human papillary muscle homogenates. CONCLUSIONS: These findings show absence of xanthine oxidase and xanthine dehydrogenase activities in human myocardium, indicating that xanthine oxidase is not a source of oxygen derived free radicals in the human heart. PMID- 1747876 TI - Release of endothelium derived nitric oxide in relation to pressure and flow. AB - STUDY OBJECTIVE: Endothelium derived nitric oxide (NO) is an important modulator of resting vascular tone. The aim of the study was to investigate the extent by which the rate of NO release is modulated by the two determinants of vascular conductance: pressure and flow. DESIGN AND EXPERIMENTAL MATERIAL: Porcine macrovascular endothelial cells cultured on microcarrier beads were used as a model in which the rate of NO release was determined photometrically. Columns packed with endothelial cell covered beads were perfused at different flow rates (2, 10, 20 ml.min-1) and perfusion pressures (ranging from 6 to 200 mm Hg). MEASUREMENTS AND MAIN RESULTS: Release of endothelial cell derived NO was continuously quantified under basal and ATP stimulated conditions using a specific difference spectrophotometric assay. Increasing flow flow from 2 to 20 ml.min-1 enhanced the basal NO release from endothelial cells fivefold. ATP (10( 4) M) augmented the NO release from endothelial cells more than 10-fold at each flow level studied. The ATP induced NO release rapidly increased by a factor of 5.8 when flow was enhanced from 2 to 20 ml.min-1 (greater than 180 pmol.min-1.mg endothelial cell protein). Raising perfusion pressure from 6 to 200 mm Hg in endothelial cells did not affect the rate of basal NO release. CONCLUSIONS: (1) The rate of NO release from endothelial cells increases when flow is enhanced. (2) Endothelial cells possess a high capacity for NO production, permitting a rapid adjustment of NO release to changes in flow. (3) The rate of NO release is not causally related to changes in perfusion pressure. PMID- 1747877 TI - Coronary pressure-flow, pressure-function, and function-myocardial oxygen consumption relations in postischaemic myocardium. AB - STUDY OBJECTIVE: The aim was to study coronary pressure-flow, pressure-myocardial wall motion and myocardial wall motion-myocardial oxygen consumption relations in postischaemic myocardium with prolonged myocardial dysfunction (stunned myocardium) in comparison with normal myocardium. DESIGN: Regional myocardial wall thickening was measured with ultrasonic crystals, and postischaemic myocardial dysfunction was achieved by occlusion of a carotid-left anterior descending coronary artery bypass (15 min) and reperfusion (30 min). Coronary perfusion pressure was decreased in 10 mm Hg steps by constricting the bypass before and after producing postischaemic myocardial dysfunction. At each constriction step, coronary flow, regional wall thickening, and regional myocardial oxygen consumption in the area perfused by the left anterior descending artery were measured. EXPERIMENTAL MATERIAL: 12 anaesthetised open chest mongrel dogs, weighing 12-16 kg, were studied. MEASUREMENTS AND MAIN RESULTS: At the basal level, myocardial wall thickening of postischaemic myocardium was depressed compared to normal myocardium, at 18.5(SD 8.9)% v 1.3(7.1)%, p less than 0.01. With coronary stenosis, wall thickening gradually decreased at a coronary pressure below 60 mm Hg in normal myocardium, but remained unchanged until mean coronary pressure was reduced to 50 mm Hg in postischaemic myocardium. Myocardial wall thickening of postischaemic myocardium was always more depressed than normal myocardium. At any level of coronary pressure, coronary flow in postischaemic myocardium was not different from normal myocardium. There was no difference in regional myocardial oxygen consumption between normal and postischaemic myocardium at any level of coronary pressure. However, regional myocardial oxygen consumption in postischaemic myocardium was higher than in normal myocardium performing similar levels of myocardial wall thickening. CONCLUSION: The coronary pressure-function relation but not the pressure-flow relation changed in postischaemic myocardium after a 15 min coronary occlusion. Regional myocardial oxygen consumption was relatively increased in postischaemic myocardium. PMID- 1747878 TI - Evaluation of factors influencing myocardial infarct size in unconscious dogs. AB - STUDY OBJECTIVE: The aim was to evaluate the factors determining myocardial infarct size in unconscious dogs. DESIGN: In anaesthetised open chest dogs, the left anterior descending coronary artery was occluded either by ligation or by thrombosis for different time periods (1.5 h, 4 h, 24 h), with or without reperfusion. Haemodynamic variables were recorded throughout the experiment. Radioactive microspheres (15 microns) were injected at the end of the ischaemic period to measure regional myocardial blood flow. Infarct size and area at risk were determined by the Evans blue triphenyltetrazolium staining technique followed by planimetry. SUBJECTS: Mongrel dogs of either sex (n = 16-42 per experiment), weight 18-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: A large interindividual variability in infarct size was observed after occlusion of the left anterior descending coronary artery at a standardised location for a well defined period. An examination of the factors responsible for this variability was carried out in order to develop a statistical model which would make it possible to predict infarct size. Using multiple regression analysis, it was found that in most protocols (except 90 min thrombosis) more than 85% of the variability in infarct size could be explained by the size of the area at risk and the amount of collateral flow. Thus, knowing the area at risk and the collateral flow, a fairly accurate prediction can be made of the size of the infarct that the dog will develop after a defined occlusion period. Furthermore, it was found that the infarct size increased with duration of occlusion, while duration of reperfusion had no effect. In the 90 min occlusion group thrombosis induced a larger final infarct than ligature. CONCLUSIONS: A correction for baseline variables is necessary in order to compare infarct size between experimental groups. The usefulness of this procedure is shown by an example of an experimental intervention, i.e., R 56,865, a drug with known cardioprotective effects. PMID- 1747879 TI - A multivariate analysis of cardiac growth in human embryos: endocardial cushions and ventricular myocardium. AB - STUDY OBJECTIVE: In view of the controversy about the morphological significance of the endocardial cushion tissue and ventricular myocardium during cardiac development, the aim was to carry out quantitative studies of these structures. DESIGN: Endocardial cushion tissue and ventricular myocardium were quantified by point count planimetry. The relative growth of the volume of these structures, and also the embryonic crown-rump length, was studied by multivariate allometry (principal components analysis) with the covariance matrix calculated from natural logarithms of the data. EXPERIMENTAL MATERIAL: 27 serially sectioned human embryos were studied, ranging from stage 15 to stage 23 (Paris collection). MEASUREMENTS AND MAIN RESULTS: The relative growth of endocardial cushion tissue, ventricular myocardium, and crown-rump length was discontinuous during the postsomitic period. The first component in principal components analysis measures overall size and, in the present analysis, accounts for 88.6% of the total variance. The growth vector isometry hypothesis was checked with the chi 2 test. This showed that differences in growth between cardiac structures and crown-rump length were allometric (p less than 0.01). Endocardial cushion tissue volume and crown-rump length grew with negative allometry during the second month of gestation, while ventricular myocardium volume grew with positive allometry. CONCLUSIONS: The results agree with those researchers who consider that endocardial cushion tissue functions only in causing initial cardiac fusion and partitioning, with little influence on the formation of definitive cardiac structures. PMID- 1747880 TI - Haemodynamic effects of arterial compliance, total peripheral resistance, and glyceryl trinitrate on regurgitant volume in aortic regurgitation. AB - STUDY OBJECTIVE: Afterload reduction is known to reduce regurgitant flow in patients with aortic regurgitation. Both arterial compliance and total peripheral resistance are determinants of afterload. The aim of this study was to evaluate the influence of arterial compliance and total peripheral resistance on the regurgitant volume. DESIGN: The values of arterial compliance and total peripheral resistance were assessed during aortic regurgitation at different regurgitant orifice areas in eight pigs before and after a bolus of glyceryl trinitrate. In a computer model the importance of arterial compliance and total peripheral resistance on the regurgitant volume was assessed by keeping each of them constant while the other variable was changed. MEASUREMENTS AND MAIN RESULTS: In both the experimental and computer models a very strong correlation was found between decreased total peripheral resistance and decreased regurgitant volume. Arterial compliance was of hardly any importance. A bolus of glyceryl trinitrate reduced regurgitant volumes and regurgitant fractions significantly. CONCLUSIONS: Total peripheral resistance is an important factor in influencing the regurgitant volumes at a given regurgitant orifice area in aortic regurgitation, while arterial compliance is of less importance. Glyceryl trinitrate effectively reduces the regurgitant volumes by its effect on peripheral resistance. PMID- 1747881 TI - Demineralization of human dentine compared with enamel in a pH-cycling apparatus with a constant composition during de- and remineralization periods. AB - A comparison was made between the demineralization of enamel and dentine with and without abraded surfaces. This was done in a pH-cycling experiment for different demineralization/remineralization ratios--in the range from 1:1 to 1:4--and for different fluoride additions (up to 2 ppm) in solution. A new automatic pH cycling system, in which the de- and remineralization solutions have a constant composition during the de- and remineralization cycles, was used to create mineral loss in human dentine and enamel. Changes in mineral content were monitored by means of longitudinal microradiography. A linear correlation was found between the amount of mineral lost and the total demineralization time for both dentine and enamel. The demineralization rates were comparable for abraded enamel and dentine and for polished enamel and dentine, and this rate was roughly doubled by the removal of the outer surface for both tissues. This showed that the presence of the outer surface is equally important to dentine and enamel. Under the pH-cycling conditions used, a logarithmic relation was found between the addition of fluoride and the decrease in demineralization for both enamel and dentine. The inhibitory effect of fluoride on demineralization was most pronounced on abraded enamel, followed by pumice-polished enamel, abraded dentine and pumice-polished dentine. About 2 ppm fluoride was needed under the conditions used to stop enamel demineralization completely; in the case of dentine, however, this amount of added fluoride did not inhibit demineralization. PMID- 1747882 TI - Fluoride, calcium and inorganic phosphorus concentrations in approximal plaque collected from young adults 1 and 24 h after toothbrushing with fluoride toothpastes. AB - A within-subject double-blind cross-over study was carried out to examine whether the chemical composition of approximal plaque was altered 1 and 24 h after brushing with fluoride toothpaste. Three fluoride toothpastes were tested, containing either sodium monofluorophosphate with calcium glycerophosphate supplement and calcium carbonate abrasive, a combination of sodium monofluorophosphate and sodium fluoride with the same supplement and abrasive or sodium fluoride with a silica abrasive. A fluoride-free toothpaste with a silica abrasive acted as the control. 19 subjects used the toothpastes separately in randomised order for 1 week each prior to collection of plaque. Contralateral half-mouth approximal plaque samples were collected 1 and 24 h after the last use of each toothpaste. Fluoride, calcium and inorganic phosphorus concentrations of plaque were estimated. The results indicated that brushing with toothpastes containing fluoride and/or calcium supplements resulted in increased concentrations of these constituents in approximal plaque 1 h after brushing. These elevated levels of inorganic ions were not observed in the samples collected 24 h after brushing. It was concluded that the potentially beneficial effect of a raised concentration of fluoride and calcium in approximal plaque observed soon after brushing is lost during the following 24 h. PMID- 1747883 TI - Optical quantification of approximal caries in vitro. AB - A fluorescent dye was applied to extracted premolars with either early artificial lesions or natural white-spot lesions. The teeth were placed in an approximal geometry, and with a specially designed fibre-optic probe the fluorescence of the dye was measured in the lesions. The same fibre-optic probe was used to measure the transmission of light at a wavelength where the dye does not absorb. This transmission of light was used to correct the fluorescence for attenuation by the intermediate layer of sound enamel situated between the probe and the lesion. Both signals varied with time because of the necessary addition of ethanol during the measurement. The mineral loss from the lesions was measured with wavelength independent microradiography (WIM) for the artificial lesions, and the optical caries monitor (OCM) for the natural white-spot lesions. The correlation coefficient between corrected fluorescence and mineral loss was r = 0.86. The results indicate that measurement of dye uptake may be a very sensitive method to diagnose early approximal caries lesions and may enable quantification of these lesions. PMID- 1747884 TI - Caries susceptibility in inbred mouse strains and inheritance patterns in F1 and backcross (N2) progeny from strains with high and low caries susceptibility. AB - We studied dental caries susceptibility in various inbred mice strains infected with Streptococcus mutans and the inheritance pattern in the F1 and the N2 backcross animals. A high caries score was observed in four laboratory strains, BALB/cAJcl, C57BL/6NJcl, C57BL/10Slc and DBA/2NJcl. Three strains, C3H/HeNJcl, AKR/JSlc and CBA/JNCrj, showed less caries. Males of strain C57BL/10Slc (mean caries score = 112.2) and females of strain C3H/HeNJcl (mean caries score = 24.0) were chosen for examinations of the inheritance of the caries susceptibility. The mean caries score in (C57BL/10Slc x C3H/HeNJcl) F1 hybrids was 98.4, demonstrating that F1 progenies were susceptible. A number of N2 mice were obtained by mating the F1 male and the C3H/HeNJcl female. The caries scores of these N2 male mice had an extensive range, from 14 to 194. Assuming that a caries score over 74 (median of the scores between C57BL/10Slc and C3H/HeNJcl) belonged to the highly caries-susceptible group, N2 mice could be divided into groups with low or high caries susceptibility. Furthermore, the effect of nu/nu mutation on caries susceptibility in mice was also examined. PMID- 1747885 TI - Cariogenicity of Milchschnitte (Ferrero GmbH) and apple in program-fed rats. AB - The cariogenicity of Ferrero Milchschnitte and apple was tested in rats using a frequency-controlled feeding machine. Twelve litters of Osborne-Mendel rats orally infected with Streptococcus sobrinus OMZ-176 and Actinomyces viscosus Ny-1 were used. Four treatment groups were tested: (1) cooked starch/sucrose 1:1 as positive control; (2) Ferrero Milchschnitte; (3) apple; (4) gastric intubation only as negative control. Groups 1-3 were additionally fed by gastric intubation with essential nutrients. Rats on Milchschnitte and apple had less fissure and smooth-surface caries than rats on a starch/sucrose diet, but significantly more than the negative controls. The Milchschnitte group exhibited less plaque extent than the positive and the negative control. The apple group showed a higher plaque extent and massively extended erosions on molar surfaces. The CFU means of S. sobrinus were decreasing from treatment 1-4. Although differences between treatments were not significant, they were associated by concomitantly decreasing caries incidence. The test foods were also assessed using intraoral plaque-pH telemetry in 6 human volunteers. Both Milchschnitte and apple were acidogenic in human telemetry. They can therefore not be regarded as safe for teeth. PMID- 1747886 TI - Optical quantitation and radiographic diagnosis of incipient approximal caries lesions. AB - The objectives of this study were to test the applicability of photocell measurements in approximal caries diagnosis and to evaluate the use of radiographs as validating criterion. Forty extracted premolars were selected, and the progression of the approximal lesions was graded clinically and radiographically by three examiners. Each tooth was transilluminated from the occlusal surface, and the throughput of light at the approximal surface was measured by a photocell. Together with clinical examination, the results of microradiographic analysis served as validating criterion in this study. The results indicate that photocell measurements can be useful in the diagnosis of incipient approximal caries lesions. Radiographs have a restricted value as validating criterion in diagnostic studies pertaining to incipient caries. PMID- 1747887 TI - Detection of occlusal caries without cavitation by visual inspection, film radiographs, xeroradiographs, and digitized radiographs. AB - The study compared visual inspection, conventional film radiographs, xeroradiographs, and digitized radiographs for the detection of caries in occlusal surfaces without cavitation. 166 extracted premolars and permanent molars without macroscopic cavitation were included. Eight observers assessed five grades of occlusal caries by visual inspection and by the three imaging techniques. Histologic sections (700-1,000 microns) served as validating criterion for the presence and depth of carious lesions, 82 teeth being found carious (27 with deep dentinal involvement) and 84 being scored as sound. Approximately 20% of the dentinal carious lesions were detected by visual inspection and 40% by conventional film radiography (both with a minimal number of false-positive observations). By xero- and digital radiography, an increasing number of false-positive scorings was seen. By digital radiography the true positive detection rate was similarly increased to 60%. The predictive values of a positive test were, on average, 0.85 for visual inspection, 0.89 for film, 0.78 for xero-, and 0.82 for digital radiography and for a negative test 0.56, 0.61, 0.61, and 0.69, respectively. However, digital radiography was able to detect over 70% of deep dentinal lesions in contrast to 45% by the other two imaging methods, without an increase in false-positive diagnoses of truly caries free teeth, compared with the other techniques. PMID- 1747888 TI - Caries prediction on the basis of past caries including precavity lesions. AB - The purpose of the present work was the construction of statistical models which allow the prediction of future high caries increments on the basis of the state of primary teeth and first molars taking into account both precavity lesions and DF experience. A child was considered to be experiencing 'high caries increment' when it had at least four new lesions (new DFS) 4 years after the first examination. Two data sets of children aged 7-10 years were analysed: (1) 803 children examined in 1980 and in 1984. The proportion of children with 'high caries increment' was 25.0%. (2) 477 children examined in 1984 and in 1988. In this group, the proportion of children with high caries increment was 16.6%. In the first group with higher prevalence of caries, sensitivity and specificity were found to be on average at 70%. In the second group, sensitivity and specificity were 77% on average. This results shows that caries prediction may be at least as successful when a 'refined' set of clinical data is used instead of a less extensive set of caries data complemented by salivary buffering capacity and microbiological data. PMID- 1747889 TI - Factors associated with active and inactive root caries in patients with periodontal disease. AB - The aim of this study was to analyze a number of microbial, salivary, and dietary factors in patients with clinically active and inactive root caries. 147 patients, aged 30-78 years, referred for specialist treatment of periodontal disease, were randomly selected. 645 decayed and 539 filled root surfaces were found. Out of the carious lesions, 372 (58%) were recorded as clinically active and 273 (42%) as inactive. 30 patients showed no lesions (group 1), 46 had only fillings or inactive lesions (group 2), and 35 showed 1-2 (group 3) and 36 greater than or equal to 3 active lesions (group 4). The lactobacillus count differed significantly between all groups, except group 1 vs. 2, and the mutans streptococcus count between groups 1 vs. 4 and 2 vs. 3 and 4. Group 4 differed in plaque score from the other groups, and the salivary buffer effect differed between the inactive groups 1 and 2 and the active group 4. By stepwise multiple regression analysis, it was shown that lactobacillus count, plaque index, salivary buffer effect, dietary habit index, and number of exposed root surfaces contributed significantly to the coefficient of determination. PMID- 1747890 TI - Active and inactive root surface caries lesions in a selected group of 60- to 80 year-old Danes. AB - In 90, 60- to 80-year-old patients with teeth retained in both jaws (mean 20.4 +/ 4.3), a total of 1,092 root surface lesions were recorded. Of these 156 were diagnosed as active caries lesions, whereas 509 were considered inactive, and 427 were filled. About 60% of the elderly had one or more active lesions and 79% had fillings. Seventy percent had more than 8 filled or carious (active or inactive) surfaces. The percentage of carious and filled root surfaces in relation to surfaces at risk demonstrated that the buccal surfaces of lower molars and premolars and upper canines were the most severely affected (RCI = 70%) with fillings predominating on easily accessible surfaces. A constant relationship between active and inactive lesions was found on all other surfaces but third molars and upper incisors. The data suggest that active and inactive root caries lesions must be diagnosed as separate entities if the dynamic nature of root surface caries is to be explored in epidemiological studies and clinical trials. PMID- 1747891 TI - Effect of intensified caries prevention on approximal caries in adolescents with high caries risk. AB - The aim of this study was to evaluate the effect of two preventive programs carried out in Public Dental Clinics for children with high caries risk. From all the 13-year-olds living in Kuopio (n = 871), 323 (37%) were selected as a high risk group on the basis of the level of salivary mutans streptococci or DS score. They were randomly divided into two groups. The first group continued with the preventive care they had received before the study. The dentists treating the children in the second group were specifically informed about their high caries risk, and instructions concerning intensified prevention were given. For comparison, half of the 13-year-olds with low caries risk were included in the study (group 3, n = 248). No special instructions concerning these children were given. After 2 years, approximal caries increment in the two risk groups was three times that of the low-risk group (2.6, 2.3 and 0.7 in groups 1-3, respectively). There was no significant difference between the two risk groups in spite of the fact that significantly more preventive procedures were provided for group 2 than for group 1. The results indicate that assessment of the subjects as high and low-risk groups was successful, but caries prevention targeted for the risk groups failed to lower the rate of caries to the same level as that of the children with an anticipated low risk. For children at high risk, the intensified prevention program monitored by dental authorities was no more successful than prevention planned by individual dentists. PMID- 1747892 TI - Plasma membrane phospholipid translocation in the mouse peritoneal macrophage: differential response to stimulation of eicosanoid production. AB - The metabolism and translocation of exogenously introduced plasma membrane phosphatidylcholine (PC) having the fluorescent fatty acid analog aminocaproyl NBD (N-nitrobenzo-2-oxa-1,3 diazole) (NBD-PC), in the sn2 position was studied in cultured murine peritoneal macrophages using biochemical and morphological techniques. Following labeling of the cell plasma membrane at 2 degrees C by vesicle lipid exchange, macrophages were warmed in the presence or absence of pharmacological stimuli of eicosanoid production and release. Fluorescence microscopy indicated that the phospholipid was translocated to an internal cellular pool upon stimulation with zymosan. In contrast, the membrane PC analog was primarily metabolized and released after being found diffusely associated with the cytoplasm in macrophages stimulated with the calcium ionophore A23187. Evidence obtained by double labeling zymosan-treated macrophages with NBD-PC and a monoclonal antibody directed against a lysosomal membrane protein demonstrated that the fluorescent lipid is internalized in association with the zymosan particles and both are found in lysosomes. The results suggest that multiple pathways exist in peritoneal macrophages which target plasma membrane PC into different cellular compartments for hydrolysis and conversion to eicosanoid products and release from cells. PMID- 1747893 TI - Morphological characteristics of the endocrine pancreas in alloxan diabetes after cyclosporin A administration. AB - Histological, immunocytochemical, morphometric and electron microscope studies were carried out on the pancreas of alloxan diabetic rats pretreated with cyclosporin A. High mortality, severe destruction of pancreatic B-cells and presence of sporadic mononuclear infiltrations in islets and around excretory ducts were observed. The results obtained show that cyclosporin A potentiates the toxic effect of alloxan on the pancreatic B-cells. PMID- 1747894 TI - Effects of steroids on human normal and otosclerotic osteoblastic cells: influence on thymidine and leucine uptake and incorporation. AB - Steroid hormones are able to influence the metabolism of bone tissue in vivo, but reports regarding their direct action on bone cells fail to agree. In this study, in vitro administration of 17 beta-estradiol, testosterone and corticosterone to normal and otosclerotic osteoblastic cells induced a drop in DNA synthesis in both populations, an increase in the neosynthesis of endocellular proteins in normal cells and a rise, mainly in proteins secreted into the medium, in otosclerotic cells. The fact that 3H-thymidine and 3H-leucine uptake were lower in otosclerotic than in normal cells suggests that the membrane permeability differs in the two populations and that steroids exert an influence on both isotope uptake and directly modulate DNA and protein synthesis. PMID- 1747895 TI - Protein synthesis in the livers of aging mice studied by electron microscopic radioautography. AB - The application of 3H-leucine results in labeling of the liver cells of mice in which protein is synthesized at various ages of the animals. Quantitative changes of protein synthesis in the hepatocytes of aging mice were studied by electron microscopic radioautography. The silver grains in the hepatocytes were mainly located over the rough surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, cytoplasmic matrix, and a few over the nuclei. The number of silver grains in the cytoplasm and nuclei of the hepatocytes gradually increased after birth, reached the maximum at 1 month after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the hepatocyte cytoplasm was more than that in nuclei at various ages. The number of silver grains in the rough surfaced endoplasmic reticulum and mitochondria gradually increased from embryo to 1 month after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the Golgi apparatus showed almost no change from fetal stage to 6 months after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the cytoplasmic matrix gradually increased from fetal stage to 2 months after birth, then decreased with aging until the 24th month. These changes reflect the quantity of protein synthesized in each cell organelle at various ages of animals. PMID- 1747896 TI - Vitellogenin gene transcription is not under strict estrogen control in winter flounder. AB - Although it is almost axiomatic that vitellogenin gene expression is under exclusive control of estrogen in oviparous animals, our results with winter flounder demonstrate that vitellogenin gene transcription in females can continue independent of estradiol. Winter flounder were hypophysectomized in January, i.e. several months after the onset of vitellogenesis. Thirty or more days after hypophysectomy, all fish had negligible levels of estradiol in the serum, and yet vitellogenin gene transcription was quite active in the liver. Our results also suggest that a pituitary factor may be involved in the normal repression of the vitellogenin gene. PMID- 1747897 TI - Appearance of lectin binding affinity to the zona pellucida during hamster oocyte maturation. AB - In our previous study, a drastic change in terminal saccharides of glycoconjugates of the hamster zona pellucida associated with oocyte maturation was observed using light microscopic methods of lectin cytochemistry. To understand the mechanism of this change, in the present study, the correlation between the cytochemical appearance of saccharide residues in the zona pellucida and nuclear maturation was examined. Immature hamsters were treated with PMSG and hCG to induce follicular development and ovulation. The animals were euthanized 0 to 26 hrs. after the injection of PMSG or 0,1,2,3,4,5,7,9 or 11 hrs. after the injection of hCG, and ovaries were dissected out, fixed, paraffin embedded and sectioned serially. Every other paraffin section was stained with hematoxylin to observe the status of nuclei and to classify follicular growth and only the fully developed preovulatory follicles were examined in experiments. The peroxidase labelled lectin-diaminobenzidine procedure was applied to sections. The lectins employed were WGA, SBA, MPA, UEA-I, LotusA and AAA. Germinal vesicle breakdown was observed within 3 hrs. after the administration of hCG. A positive reaction of WGA, SBA or MPA for zonae pellucidae in the fully developed preovulatory follicles appeared 1 hr. after hCG injection, and remained so for the next 10 hrs. UEA-I, Lotus A and AAA reactions were negative for all of the zonae pellucidae observed. The data indicate that the synthesis of saccharide residues such as GlcNAc and GalNAc forming zona components in the follicles is not triggered by germinal vesicle breakdown. PMID- 1747898 TI - Multivariate data analysis in biochemistry: a new integrative approach to metabolic control in brain aging. AB - The principal component analysis (PCA) allows to obtain a quantitative measure of the state of metabolism as a whole. In this paper we applied this method to the study of energy metabolism during aging process and of the effect of a drug (Acetyl-1-carnitine, ALCAR) on the aging brain. PMID- 1747899 TI - Localization of yolk proteins and their possible precursors using polyclonal and monoclonal antibodies, in Helix aspersa. AB - Three major yolk proteins of 140, 100, 80 KD and a faint band of 440 KD were determined by gradient gel electrophoresis in the mature eggs of Helix aspersa. Polyclonal and monoclonal antibodies were raised against mature oocyte extracts. The binding sites of these rabbit and hybridoma antibodies with the different yolk protein components were identified with a combination of WESTERN blotting, ELISA, immunofluorescence and immunogold staining. All these techniques demonstrated materials immunologically similar to vitellins in the hemolymph and in the glandular cells of the digestive gland. The data suggest that, for its vitellogenesis, the garden-snail utilizes a heterosynthetic mechanism similar to that known in oviparous animals. The vitellogenins would be produced by the digestive gland. PMID- 1747900 TI - Diabetes mellitus in sand rats (Psammomys obesus): microangiopathy during development of the diabetic syndrome. AB - The purpose of the study was to investigate the development of microangiopathic complications in North African sand rats with diabetes induced by a long-term standard laboratory diet. Hyperinsulinaemic rats, whether non-diabetic obese or diabetic, developed capillary basement membrane (CBM) thickening in the skin; in insulin-dependent animals, this change was diffuse. Many PAS positive areas were demonstrated in skeletal muscle and myocardium, together with evidence of microangiopathy; the primary myocardial lesion in insulin-dependent disease was ischaemic fibrosis. The kidney was also affected with marked basement membrane thickening in Bowman's capsule and glomerular capillaries; glomerulosclerosis and tubular changes were found in insulin-dependent disease. No evidence of diabetic retinopathy was found, and there was a high incidence of cataract. PMID- 1747901 TI - [Tobacco addiction and its treatment using replacement therapy]. AB - Tobacco or nicotine dependence is now established as a disease and listed by several countries and by the World Health Organization. The characteristics and mechanisms of tobacco dependency will be described as well as its assessment and implications for treatment. PMID- 1747902 TI - [Differential diagnosis of pleural effusions. Experience from a clinical study 1986-1990]. AB - In a group of 171 patients with pleural effusions included in a perspective study at the Second Clinic for Tuberculosis and Respiratory Diseases in Prague in 1986 1990, the authors evaluated the asset of examination methods for the diagnosis of different types of effusions. They compared differences between the group of patients with effusions associated with neoplastic diseases (group 1-108 subjects) with a group of patients with other types of effusions (group 2-63 subjects). They compared data in the case-history, physical examination, examination of the effusions and other auxiliary examinations. For significantly different parameters of blood examination (CEA, TPA, IgM, LDH) and the effusions (CEA, IgM, ALP) liminal values, specificity and sensitivity were assessed for differentiation of tumourous and other types of exudates. The authors compared also the required time and method of diagnosis in the two groups of patients. In group 1 cytology of the exudate, biopsy of the pleura and bronchoscopy were most valuable. In patients of group 2 in addition to the cytology of the exudate, biochemistry and bacteriology and auxiliary examinations were most important. The number of necessary diagnostic "steps" for assessment of the aetiology of exudates differed. Fewer steps were necessary for assessment of tumourous exudates. The groups differed as to treatment and survival of the patients. PMID- 1747903 TI - [Possibilities of psychotherapy in the comprehensive treatment of bronchial asthma]. AB - Asthma bronchiale, as all long-lasting diseases with unpleasant subjective complaints, has a considerable psychic superstructure. It is known that in chronic asthmatic patients psychic influences alone can provoke an attack. The extent and severity of mental factors in the pathogenesis of asthma can be revealed by psychological examination. By aimed psychotherapy the patient's complaints can be mitigated and it is possible to improve his quality of life. The authors give an account of principles they apply during psychotherapy and problems they encounter. The results are documented by selected case-histories. The patients' tolerance of physical work increases, the drug consumption declines as well as the number of sickness days and the length of hospitalization. The authors recommend therefore that psychological examination should be part of examinations of asthmatics and that in selected patients treatment should be supplemented by psychotherapy. PMID- 1747904 TI - [Energy requirements in women during pedalling on a bicycle ergometer]. AB - The bicycle ergometer is the most frequently used equipment for loading tests for the purpose of functional diagnosis and for the purpose of locomotor rehabilitation. The energy required to meet this locomotor activity is within a wide range of load intensities which depends linearily on the intensity of pedalling. The steepness of this linear relationship which characterizes the degree of adaptation of the organism to this type of locomotor activity is the smaller the more the investigated subjects are adapted to the load. In general it depends on the degree of training, age, sex, strength, pedalling frequency, on the load protocol and on the biomechanical conditions during pedalling (e.g. the height of the saddle). Based on our measurements in a group of untrained women of different age and in trained women of different age it can be demonstrated that all individual relations between energy characterized by means of VO2 and the intensity of the load - P is within the zone where the upper borderline is formed by the equation VO2(ml) = 11.00.P (W) + 403 and the lower borderline by VO2(ml) = 9.90.P (W) + 252. The basic relationship, independent on the degree of training, age and strength, valid in the zone of pedalling frequencies of 60-80 rot. min-1 and in the zone of load intensities of 75-325 W has the shape of VO2(ml) = 10.60.P(W) + 269. The maximum error of assessment of VO2 by means of the load intensity is 9% or less. PMID- 1747905 TI - [Mechanism of growth of giant intracranial vascular aneurysms. Its demonstration using computer tomography and angiography]. AB - The authors demonstrate three patients with gigantic intracranial aneurysms diagnosed by computed tomography (CT) and angiography (AG). The aneurysm was visualized on the CT as an expansive isodense to slightly hyperdense focus with a sharp hypodense borderline. After administration of the contrast substance the small focus was stained centrally or the slightly excentrically located focus (non-thrombotized portion of the aneurysm); the thrombotized portion of the aneurysm does not change, borders of the aneurysm are more marked (pseudomembrane, highly vascularized fibrous tissue). A number of authors describe findings confirmed on surgery or necropsy where haemorrhage into aneurysmal wall is apparent. Those findings suggest a similar mechanism of growth of the gigantic arterial aneurysm, as assumed in chronic subdural haematomas and encapsulated growing intracranial haematomas. It is assumed that haemorrhage into the aneurysmal wall is covered by a fibrous membrane into which further haemorrhage may occur, the entire cycle is repeated and thus the aneurysm grows. The clinical symptoms are due to the expansive character manifested only when the aneurysm has reached a certain size. PMID- 1747906 TI - [Evaluation of research, educational and therapeutic-preventive activity of medical school faculty members]. PMID- 1747907 TI - Fine structure of the glomerular basement membrane of the rat kidney visualized by high-resolution scanning electron microscopy. AB - The fine structure of the glomerular basement membrane (GBM) of the rat kidney was studied by means of high resolution scanning electron microscopy. Specimens were taken from kidneys perfused with paraformaldehyde, freeze-fractured and then processed with conductive staining. The fractured surface of glomerular tufts exhibited the inner and outer surface of the GBM uncovered by endothelial and epithelial cells. The lamina densa was composed of densely packed granular material together with scattered fibrils. The laminae rarae interna and externa were composed of a meshwork that showed some structural heterogeneities. The meshwork composing the lamina rara interna contained 5- to 9-nm-thick fibrils, had pores 11-30 nm wide, and was associated with granular material except in those places that corresponded with endothelial fenestrae. The meshwork of the lamina rara externa was made up of 6- to 11-nm-thick fibrils, and had smaller pores under the foot processes (10-24 nm wide) than those near the filtration slits (16-32 nm wide). In addition to the meshwork, the lamina rara interna contained microfibrils that were arranged differently depending on the topography of the capillary wall: scattered fibrils had no predominant orientation at the convex side, circumferential bundles lay at the concave side of the peripheral capillary wall, and had a circumferential arrangement in the paramesangial wall. PMID- 1747908 TI - Structural heterogeneity of the basement membrane in the rat proximal tubule. AB - The ultrastructure of the basement membrane of the rat proximal tubule was observed by transmission electron microscopy after the use of a cold dehydration technique. The basement membrane of the P1 segment is thick and possesses several structural specializations that are rare in other basement membranes; these include intraepithelial ridges, dense bars, and basement membrane vesicles. The intraepithelial ridges are found in the intercellular spaces between interdigitating processes of the proximal tubule cells. The ridges and the interdigitating processes run circumferentially around the tubule. The dense bars are frequently found in the intraepithelial ridges. They are especially prominent on the concave side of the tubular bends and to a lesser extent near sites where intracellular actin filaments anchor onto the basal cell membranes. The basement membrane vesicles are bounded by unit membranes; they are variable in both their electron density and their size. They are usually found in association with dense bars, and the grade of their accumulation is positively correlated with the development of the dense bars. These three specializations have no topographical relationship with the interstitial structures, such as fibroblasts and collagen fibrils. The specializations are best developed on the concave side of tubular bends where the circumferential stresses caused by the intraluminal hydraulic pressure are presumably the largest; we therefore propose that they are an adaptation to, or a manifestation of, the increased wall stress in the proximal tubule. PMID- 1747909 TI - Convertible adipose tissue in mice. AB - Ability to express uncoupling protein (UCP) and establish UCP-dependent thermogenesis was analyzed in anatomical areas of mice that are generally considered to be white adipose tissue: mesenterial, perimetral, epididymal, inguinal, and superficial layer of interscapular white adipose tissue. The mice were acclimatized for 1 week to 4 degrees C; the following week they were exposed to cold stress (1 h at -20 degrees C, 2-3 times daily). In such conditions in inguinal adipose tissue, slot-blot analysis detected significant amount of UCP mRNA and lipoprotein lipase mRNA. Immuno-electron-microscopic localization of UCP showed that developed mitochondria of cold-stressed inguinal adipocytes contained UCP in the same amount as uncoupled (UC)-mitochondria of brown adipocytes. Morphological and morphometrical analysis showed that such inguinal adipose tissue appeared as brown adipose tissue. Since in control mice, inguinal adipose tissue was UCP-negative and tissue appeared as white adipose tissue, the duration of this white-to-brown adipose tissue conversion was analyzed. Mice, cold stressed for 1 week, were rewarmed at 28 degrees C and their inguinal adipose tissue was analyzed in comparison with interscapular brown adipose tissue and epididymal white adipose tissue for another 37 days. During that time inguinal adipocytes ceased expressing UCP mRNA; UC-mitochondria in inguinal adipocytes were destroyed and replaced with common, C-mitochondria; and UCP was undetectable immunohistochemically. Adipocytes accumulated lipids, and the tissue morphologically once again resembled white adipose tissue. Described changes showed that besides typical brown and white adipose tissue in mice, there existed a third type of adipose tissue described as convertible adipose tissue. PMID- 1747910 TI - Three-dimensional architecture of the human myosalpinx isthmus. Scanning electron microscopy after NaOH digestion and ultrasonic microdissection. AB - The three-dimensional architecture of the human isthmic myosalpinx is directly visualized by means of scanning electron microscopy after removal of interstitial connective tissue through NaOH maceration and ultrasound microdissection. These investigations show that the myosalpinx is composed of irregularly running bundles of smooth muscle cells, changing their orientation within the myosalpinx and displaying longitudinal, oblique and circular directions. The muscular bundles anastomose and intermingle with other bundles running at different levels in the oviduct wall, and actually give rise to a wide and complex muscular network in which no distinct layers are readily discernible. These morphological data are consistent with the physiological findings that the transport of gametes and embryo in very early stages in the isthmic portion of the oviduct tube is the result of a discontinuous pattern of forward and backward movements. PMID- 1747911 TI - Immunohistochemical distribution of sulfhydryl oxidase in the human testis. AB - Sulfhydryl oxidase (SOx) is an enzyme that catalyzes the oxidation of sulfhydryl compounds. It is present in mitochondria of certain testicular cells at specific stages of functional activation. In the mature human testis moderate SOx immunoreactivity is found in Leydig cells, and lacking in Sertoli and in peritubular cells. The Adark spermatogonia usually contain immunoreactive mitochondria, while in Apale spermatogonia immunoreactivity is mostly low. In stage V of spermatogenesis, Apale spermatogonia were found containing immunoreactive material. Leptotene (stages IV and V) and zygotene (stage VI) primary spermatocytes display a moderate immunoreaction. It is strongest in pachytene spermatocytes of stages I-IV, decreases in stage V, and is low during diakinesis and in secondary spermatocytes. Late spermatids usually show a stronger immunoreactivity than early spermatids. At stage V of spermatogenesis the late spermatids contain only few immunoreactive particles. Spermatozoa are free of SOx-immunoreactive mitochondria. In residual bodies small amounts of SOx immunoreactive particles are seen. Compared to rat and hamster testis, SOx immunoreactivity of the human testis is less clearly stage-dependent and it is not confined to certain germ cell stages. As deduced from the findings in patients with spermatogenic disorders, the SOx immunoreactivity of spermatogonia in human testis seems to be of diagnostic relevance. PMID- 1747912 TI - Morphological alteration of gut-associated lymphoid tissue after long-term total parenteral nutrition in rats. AB - The morphological alteration of gut-associated lymphoid tissue (GALT) induced by long-term absence of dietary stimulation was investigated. Male Wistar rats weighing approximately 230 g were maintained with total parenteral nutrition (TPN). Control rats were allowed to have the same amount of the solution orally. After two weeks, the morphological alteration of GALT was examined. Although no significant difference in weight gain was noted between the two groups, the area comprised by Peyer's patches was decreased in TPN rats. The number of transported lymphocytes and the ratio of helper T (Th) cells to suppressor/cytotoxic T (Ts/c) cells in intestinal lymph were lowered after TPN treatment. In an immunohistochemical study of the rat ileum, the number of T cells and the Th/Ts/c ratio were decreased both in the intraepithelial spaces and in the lamina propria of TPN rats. The percentage of interleukin-2 receptor-positive cells and the number of IgA-containing cells in the lamina propria were significantly reduced in TPN rats. These results suggest that dietary stimulation might play a role in the maintenance of GALT function and morphology. PMID- 1747913 TI - Diversity of ultrastructure in different phenotypes of cultured microvessel endothelial cells isolated from bovine corpus luteum. AB - Five different types of cultured microvessel endothelial cells defined by use of light microscopy and scanning electron microscopy in a preceding study were investigated by transmission electron microscopy. Type-1 cells displayed a deep invagination of the cell membrane or a single cilium. Granules of low electron density were abundant. A perinuclear ring of intermediate filaments occurred. Cultures of type-2 cells were subdivided into phenotype A, reminiscent of cell type 1, and into phenotype B, assumed to be vascular smooth muscle cells. Many highly electron-dense granules appeared in late postconfluent cultures of both phenotypes. Cell-type 3 was conspicuous because of a large intracytoplasmic vacuole. Lysosomes with curvilinear bodies were found in cell-types 3 and 4. Both cell types developed a peripheral regular network of microfilaments. Cell-type 5 showed vesiculation of the rough endoplasmic reticulum, lipid droplets and a peripheral felt-like belt of microfilaments. Tubular forms seen in late postconfluent cultures of cell-types 1 to 3 displayed a core of extracellular matrix. Pseudotubular forms of cell-type 4 contained apoptotic bodies. Thus, as seen at the ultrastructural level, different features are maintained by cultured microvessel endothelial cells, suggesting that they have different inherent properties. PMID- 1747914 TI - Light- and electron microscopy of isolated vestibular hair cells from the guinea pig. AB - Cells isolated from the guinea-pig vestibular sensory epithelia were studied using light- and electron-microscopic techniques. The cells maintained their characteristic shapes when they had been separated. Mammalian vestibular cells are traditionally divided into two classes, type-I and type-II hair cells. It was, however, found that the population of isolated cells consisted of hair cells with a striking variability in shape and size. This was most conspicuous for the type-I hair cells. Isolated hair cells processed for electron microscopy showed that the isolation process caused minor ultrastructural damage but that the separation often was incomplete in that the large calyx-like nerve endings were still attached to type-I cells. The results suggest that the distinction of only two classes might be insufficient to describe mammalian vestibular hair cells. PMID- 1747915 TI - Formation of hair follicles from a single-cell suspension of embryonic rat skin by a two-step procedure in vitro. AB - A technique for culturing skin was devised whereby hair follicles in a normal state were generated from a single-cell suspension of embryonic rat skin. Dissociated cells obtained by trypsinization of the day-15 embryonic lip were cultured by a two-step procedure in vitro. Reorganization of hair-follicle rudiments was accompanied by reaggregation of the cells during a 24-hour initial culture with rotation, and the rudiments differentiated into hair follicles within a week during subsequent subculture of the cell aggregates by floatation. The light-microscopic features and the size of the follicles were similar to those of day-18 vibrissa follicles during normal development in vivo. Furthermore, the stratification of cells, including subcellular differentiation, and the ultrastructure of the hair follicles generated in vitro were similar to those of normal hair follicles with well-keratinized hair shafts. The present system appears to be a useful model for analytical studies in vitro on the formation of hair follicles and for studies designed to facilitate the transplantation of human hair. PMID- 1747916 TI - Anatomical mapping of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in outer hair cell efferents in adult rats. AB - The distribution of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in the cochleae of 15 adult Wistar white rats was investigated using the peroxidase-antiperoxidase (PAP) technique. A monoclonal antibody to ChAT and a polyclonal antiserum to GAD were used. Immunoreaction was investigated quantitatively, in the electron microscope, on tangential sections of the tunnel of Corti and the rows of outer hair cells. ChAT like and GAD-like immunoreactivity was found in all efferent nerve fibres in the tunnel of Corti and in all efferent synapses on the outer hair cells. A coexistence of ChAT and GAD in the efferent system to the outer hair cells of the rat is therefore assumed. PMID- 1747917 TI - Developments and perspectives on the role of cytochrome P450s in chemical carcinogenesis. PMID- 1747918 TI - Enhanced lipid peroxidation in rat gastric mucosa caused by NaCl. AB - The effects of NaCl on lipid peroxidation levels in gastric mucosa and urine were investigated in male Wistar rats. The animals were fed NaCl-supplemented diet at concentrations of 4.0, 2.0, 1.0, 0.5, 0.25 and 0% (control) for 5 weeks. Further groups were maintained on the 4.0 or 0% NaCl diets and simultaneously administered 20 p.p.m. indomethacin dissolved in the drinking water. When the rats were killed, a dose-related increase of malondialdehyde (MDA) was found in both gastric mucosa and urine, the urinary MDA levels clearly correlating with those for stomach tissue. Cell proliferation of fundic mucosa was also significantly increased in rats fed 4.0 or 2.0% NaCl-supplemented diet. Indomethacin suppressed the 4% NaCl-associated MDA increase in both gastric mucosa and urine as well as the elevation in cell proliferation. The results clearly show that administration of NaCl, a gastric tumor promoter, is associated with enhanced lipid peroxidation in the gastric mucosa. PMID- 1747919 TI - Benzo[a]pyrene-globin adducts detected by synchronous fluorescence spectrophotometry: method development and relation to lung DNA adducts in mice. AB - A simple synchronous fluorescence spectrophotometry (SFS) to detect benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-globin adducts is described. SFS for BPDE-DNA, which measures detached benzo[a]pyrene (B[a]P)-tetrols after acid hydrolysis of DNA, was applied for BPDE-globin adducts in B[a]P-treated C57BL/6 (B6) mice. Unlike DNA samples, globin is not measurable as such after acid hydrolysis because proteins give a background in SFS. Furthermore, proteinase incubation before acid hydrolysis of globin gave too much background even after purification to be useful in this assay. Of several purification procedures tried after acid hydrolysis (protein precipitation, elution through Sep-Pak C18, filtration, ether extraction of tetrols), the lowest background fluorescence was obtained with ether extractions of B[a] moieties. Ether phases were evaporated to dryness and the remainder dissolved in distilled water (1 ml), which was measured by SFS. Compared to DNA, somewhat milder hydrolysis conditions were optimal for globin samples (0.05 M HCl, 1.5 h, + 90 degrees C). Globin samples from B[a]P treated mice gave a peak at the same wavelength (345 nm excitation) as the hydrolysis products of BPDE-DNA adducts, indicating B[a]P-tetrols and triols in the sample. Less than half of B[a]P measured in globin was from covalently bound BPDE. In mice injected i.p. with 1-160 mg/kg of B[a]P there was a dose-dependent increase in the amount of BPDE adducts in globin and a positive correlation with lung and liver DNA. Globin adducts were a more sensitive indicator of B[a]P exposure than DNA adducts because more globin can be used for the assay. Although both covalently and non-covalently bound BPDE in globin are detected by SFS, this method is the simplest described so far, reproducible and theoretically sensitive enough for human biomonitoring. PMID- 1747920 TI - A three-dimensional molecular template for substrates of human cytochrome P450 involved in debrisoquine 4-hydroxylation. AB - A three-dimensional molecular template has been generated for substrates of human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6). This template defines the stereochemical requirements for CYP2D6 substrates in terms of the volume occupied and positions of key atoms. The modelling was based on the X-ray crystallographic coordinates of the location of the attacked C5 atom of camphor in relation to the haem in cytochrome P450 cam. Interactive molecular graphics combined with energy calculations were used to identify allowed conformers to superpose known CYP2D6 substrates to yield a molecular template. This model takes into account the site of attack of the known substrates and the requirement for a protonated nitrogen atom to interact with an anion site of the protein. A nitrogen-anion distance of between 2.5 and 4.5 A was allowed for the interaction. The substrates modelled were cardiovascular drugs (debrisoquine, sparteine, guanoxan and perhexiline), beta-adrenergic blocking agents (bufuralol and propranolol), tricyclic anti depressants (desipramine, amitriptyline and nortriptyline) and other miscellaneous compounds (phenformin, methoxy-amphetamine, codeine and dextromethorphan). The template generated in this manner was then used to determine the likelihood that certain other compounds were substrates for CYP2D6. A carcinogenic protein pyrolysate product, 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP), did not fit the template and is therefore unlikely to be activated by this enzyme. A potent carcinogen in tobacco smoke, 4-(N-methyl-N nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), fitted the template but could not be modelled to form a favourable nitrogen-anion interaction. Experimental substrate competition studies also showed that NNK is unlikely to be a CYP2D6 substrate. It was also shown that the widely used drug for treatment of breast cancer, trans-1 (4-beta-dimethylaminoethoxyphenyl)-,2-diphenyl-1-ene (tamoxifen), did not fit the molecular template and is unlikely to be metabolized by CYP2D6. Coordinates of the template are available. PMID- 1747921 TI - The crystal and molecular structure of ellagic acid dihydrate: a dietary anti cancer agent. AB - The crystal and molecular structure of ellagic acid dihydrate has been determined by X-ray diffraction techniques. This acid inhibits the carcinogenic properties of a variety of chemical compounds including benzo[alpha]pyrene-7,8-diol-9,10 epoxide, aflatoxin B1, N-methyl-N-nitrosourea, 3-methyl-cholanthrene and 7,12 dimethylbenz[alpha]anthracene. Ellagic acid dihydrate forms triclinic crystals with unit cell dimensions: a = 7.656(1) A, b = 9.563(1)A, c = 4.623(1) A, alpha = 97.88(1) degrees, beta = 103.2(1) degrees, gamma = 102.22(1) degrees, V = 315.9 A3, space group = P1. There is a center of symmetry in the crystal coinciding with the center of the molecule, so that there is only one molecule in the unit cell. Ellagic acid is planar and molecules are interconnected by hydrogen bonds to water, giving rise to layers of molecules throughout the crystal. Its activity and anti-cancer properties are compared with those of a similar naturally occurring compound, quercetin. PMID- 1747922 TI - Evaluation of the in vivo genotoxicity of the structural analogues 2,6 diaminotoluene and 2,4-diaminotoluene using the rat micronucleus test and rat liver UDS assay. AB - The two structural isomers 2,4- and 2,6-diaminotoluene (DAT) differ in their carcinogenic properties; the 2,4-isomer is carcinogenic in rats and mice, whereas the 2,6-isomer has been reported to be non-carcinogenic. Both isomers were reported to be mutagenic in Salmonella typhimurium in the presence of S9, which was confirmed in the present study before in vivo assays were commenced. Both isomers were tested in the rat bone marrow micronucleus test and the rat liver UDS test to investigate how well these assays discriminate between the carcinogenic and the non-carcinogenic isomer. In the micronucleus test both isomers gave weakly positive results; however, with the carcinogen 2,4-DAT this weak effect was only detectable at very toxic doses and therefore the biological relevance of this result is questionable. Thus, the micronucleus test did not discriminate correctly between the carcinogen and the non-carcinogen. With the liver UDS test, discrimination was achieved but the positive effect seen for the carcinogenic isomer was weak and dependent on the method of preparation of the dosing suspensions. The results are discussed in relation to the carcinogenicity data on both compounds. It is concluded that although both isomers are potent genotoxins in vitro they exert their genotoxic potential only weakly in vivo and convincing discrimination between the carcinogenic and non-carcinogenic isomer was not demonstrated. PMID- 1747923 TI - Formation of a glutathione conjugate and a semistable transportable glucuronide conjugate of N2-oxidized species of 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) in rat liver. AB - We have previously shown that 2-hydroxamino-1-methyl-6-phenylimidazo[4,5 b]pyridine(2-h ydroxamino-PhIP) is the principal metabolite leading to mutations in Salmonella typhimurium TA98 and DNA damage in mammalian cells. In rat hepatocytes this metabolite can be further conjugated to 2-(N-beta-D glucuronopyranosyl (hydroxamino)-1-methyl-6-phenylimidazo[4, 5-b]pyridine[N(OH) gluc-PhIP]. Its rate of formation was increased in hepatocytes from polychlorinated biphenyl (PCB)-pretreated animals. This metabolite is the main metabolite of PhIP in bile and it is hydrolyzed both by human and rat intestinal bacteria. Smaller amounts are excreted into urine. The evidence for the proposed structure is based on 1H- and 13C-NMR, beta-glucuronidase-lability giving 2 hydroxamino-PhIP upon hydrolysis and on the results obtained by using biochemical enzyme inhibitors. N(OH)-gluc-PhIP may be important for genotoxic lesions and tumors of 2-amino-1methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in extrahepatic tissue. In hepatocytes and bile from PCB-pretreated rats a PhIP-glutathione conjugate, 2-glutathionyl-1-methyl-6-phenylimidazo[4,5-b]pyridine (GSH-PhIP) was also found. The evidence for the proposed structure is based on 1H-NMR and high resolution mass spectrometry. The metabolite can also be produced by a direct nucleophilic substitution of the nitro group in 2-nitro-PhIP by glutathione (GSH) in vitro. The metabolite did not form from 2-hydroxamino-PhIP and GSH either directly or in the presence of glutathione S-transferase. The formation of GSH PhIP in rat liver and isolated cells only at a high rate of 2-hydroxamino-PhIP formation (PCB-treated animals) indicates that 2-nitro-PhIP may be formed in the liver during such N-oxidation of PhIP. PMID- 1747924 TI - Role of DNA replication in carrier-ligand-specific resistance to platinum compounds in L1210 cells. AB - L1210 cell lines have been described that are sensitive to most platinum compounds (L1210/0), resistant to ethylenediamine (en)-Pt but sensitive to diaminocyclohexane (dach)-Pt (L1210/DDP), and resistant to dach-Pt but sensitive to en-Pt (L1210/DACH). We have examined the effect of the dach and en carrier ligands on the ability of Pt-DNA adducts to inhibit DNA replication. Alkaline sucrose gradient sedimentation was used to determine the influence of both carrier ligands on the inhibition of replicon initiation and DNA chain elongation. Initiation of replicons was inhibited by Pt-DNA adducts to a greater extent than chain elongation in all three cell lines. Inhibition of replicon initiation was affected by the nature of the platinum carrier ligands only in the L1210/DACH cells in which 7.8-fold more dach-Pt adducts than en-Pt adducts were required to reach 63% inhibition. However, a strong carrier ligand effect was observed on the inhibition of DNA chain elongation in both the L1210/DDP and L1210/DACH cell lines. The L1210/DDP cell line required 4-fold more en-Pt adducts than dach-Pt adducts to inhibit DNA chain elongation by 63%. In the L1210/DACH cell line, 2.7-fold more dach-Pt adducts than en-Pt adducts were required for 63% inhibition. The L1210/0 cell line demonstrated no carrier ligand specificity for inhibition of chain elongation. Significant replicative bypass of Pt-DNA adducts was observed even in the L1210/0 cell line in that greater than 50 Pt-DNA adducts per 100 kb were required for 63% inhibition. The same level of inhibition was reached with 1.25 adducts of benzo[a]pyrene diolepoxide I per 100 kb. These data suggest that L1210 cells are capable of substantial replicative bypass of Pt-DNA adducts. Furthermore, the bypass of Pt-DNA adducts is increased in resistant L1210 cells and is markedly dependent on the nature of the platinum carrier ligand. PMID- 1747925 TI - Distribution of cytochrome CYP2E1 in murine liver after ethanol and acetone administration. AB - The effects of acetone and ethanol administration on cytochrome CYP2E1 in murine liver were investigated. A monoclonal antibody (Mab 1-98-1) specific to rat ethanol-inducible P450 recognized a major band of Mr 51,000 in Western immunoblots of mouse liver microsomes. This band was increased 1.8-fold by 10% ethanol in drinking water for 2 weeks, 4.7-fold by 1% acetone in drinking water for 1 week, and 2.5-, 2.1- and 6.8-fold by ethanol in a liquid diet for 9 days, 2 weeks and 3 weeks respectively. Immunohistochemical staining experiments with the same antibody showed specific localization in centrilobular regions of liver lobules, with variations in intensity that corresponded to differences detected in Western immunoblots. Uniform cellular increases in centrilobular staining occurred with all ethanol treatments, whereas a more heterogeneous increase in individual cells was noted after acetone. Lipid accumulation in hepatocytes was pronounced after 3 weeks on the ethanol liquid diet but was less so in other treatment groups, and thus did not consistently correlate with enzyme induction. Microsomal aniline p-hydroxylase activity was also induced by the acetone and ethanol treatments, with a progressive increase from 9 days to 3 weeks on the ethanol liquid diet. Changes in this activity in general paralleled those found with immunohistochemistry and immunoblotting. The results demonstrate that (i) the mouse is a good model for correlative biochemical and histochemical studies of CYP2E1 induction, (ii) in the mouse liver, this P450 is preferentially localized in centrilobular regions constitutively as well as in induced states, (iii) the centrilobular pattern varies under different induction conditions, and (iv) there is a progressive inductive increase in CYP2E1 protein and enzyme activity with chronic ethanol treatment over at least 3 weeks. PMID- 1747926 TI - Glutathione S-transferase mu in human lymphocyte and liver: role in modulating formation of carcinogen-derived DNA adducts. AB - Glutathione transferase (GT) activity towards trans-stilbene oxide (tSBO), benzo[a]pyrene-4,5-oxide (B[a]PO) and 1-chloro-2,4-dinitrobenzene (CDNB) was measured in human liver and lymphocytes. GT-tSBO activity is catalyzed by GT mu which has polymorphic expression in human lymphocytes. Our results show that activity of GT-tSBO in lymphocytes correlates with its activity in liver (r = 0.7, P less than 0.001). GT activity towards BPO (GT-BPO) also correlated with GT tSBO in lymphocytes and liver. However, interindividual variation of GT-BPO is less than that of GT-tSBO, suggesting that BPO may not be as specific a substrate for GT mu and therefore other GT isozymes may contribute to BPO conjugation. Conjugation of CDNB by GT was not different using cytosols from either high or low GT mu individuals. The functional significance of the GT-mu polymorphism was evaluated by measuring its effect on benzo[a]pyrene (B[a]P)- and aflatoxin B1 (AFB1)-DNA adduct formation in vitro. Human liver cytosols prepared from persons having low or high GT-tSBO activity were incubated with human liver microsomes, calf thymus DNA and B[a]P or AFB1. HPLC analysis revealed that the major B[a]P adduct was dG(N2)-7 beta, 8 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-dG). BPDE-dG adducts were decreased equally by cytosols from either low or high conjugators. In contrast, AFB1-DNA binding was inhibited to a greater extent in high conjugators than low conjugators. HPLC analysis demonstrates that adducts formed were AFB1-FAPyr and AFB1-N7-Gua. The correlation between AFB1-DNA adduct concentrations and GT mu activity was highly significant with a correlation coefficient of r = 0.88 at P less than 0.001. These results suggest that GT mu plays an important role in detoxifying DNA reactive metabolites of AFB1 and this enzyme may be a susceptibility marker for AFB1 related liver cancer. Moreover, our data demonstrate that lymphocytes are a reliable surrogate tissue for detecting liver GT mu polymorphisms. PMID- 1747927 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by cytochrome P450IIB1 in a reconstituted system. AB - Several previous studies have suggested that cytochrome P450IIB1 is involved in the bioactivation of the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), in rats as well as in mouse lung microsomes. The present investigation was undertaken to study the metabolism of NNK by purified cytochrome P450IIB1 in a reconstituted system. The metabolites 4-hydroxy-4-(3 pyridyl) butyric acid (hydroxy acid), 4-oxo-4-(3-pyridyl) butyric acid (keto acid), 4-oxo-4-(3-pyridyl) butanol (keto aldehyde), 4-(methylnitrosamino)-1-(3 pyridyl-N-oxide)-1-butanone (NNK-N-oxide) and 4-oxo-4-(3-pyridyl)-1-butanol (keto alcohol) were quantitated by HPLC. The results showed that, in addition to alpha hydroxylations, cytochrome P450IIB1 also catalyzed the formation of NNK-N-oxide efficiently, and to a certain extent, the conversion of NNK primary hydroxylation metabolites (keto aldehyde and keto alcohol) to secondary metabolites (keto acid and hydroxy acid). Cytochrome b5 at a ratio of 1:1 or 2:1 to P450IIB1 had no significant effect on the metabolic activities and profiles of NNK. The apparent Km values for the formation of keto aldehyde, NNK-N-oxide and keto alcohol were respectively 191.2, 131.4 and 318.0 microM with corresponding apparent Vmax values of 89.7, 295.5 and 333.3 pmol/min/nmol P450, indicating that hydroxylation at the alpha-methyl position is preferred over the alpha-methylene position. Measurement of formaldehyde, a product derived from the alpha-methyl hydroxylation, was developed as a convenient method to study NNK metabolism. Thiourea activated cytochrome P450IIB1-catalyzed NNK metabolism significantly. Phenethyl isothiocyanate, an inhibitor of NNK-induced lung carcinogenesis, inhibited P450IIB1-catalyzed NNK demethylation in a concentration-dependent manner. This work demonstrates that purified P450IIB1 can catalyze the conversion of NNK to most of its oxidative metabolites. PMID- 1747928 TI - 3-Methyladenine mutagenesis under conditions of SOS induction in Escherichia coli. AB - Under conditions of the induced error-prone SOS response in Escherichia coli, N methyl-N-nitrosourea (MNU) was found to produce a majority of mutations at A.T base pairs. These mutations included mainly A.T----G.C transitions, followed by A.T----T.A transversions and (-1)A.T frameshifts. The possibility that 3 methyladenine (3-MeAde) significantly contributed to these mutations was investigated. MNU mutagenesis under SOS conditions was studied in E. coli strains deficient in 3-MeAde-DNA glycosylase I (TagI), which is the major constitutively expressed repair enzyme for 3-MeAde. In SOS uninduced cells, the lack of 3-MeAde repair did not increase mutagenesis, suggesting that 3-MeAde does not contribute to mutagenesis under these conditions. In SOS-induced cells, by contrast, MNU induced a 5-fold higher mutation frequency in the TagI-deficient cell strains, suggesting that 3-MeAde is indeed an SOS-dependent premutagenic lesion. Although 3-MeAde is mutagenic under SOS conditions, it is possible that its fast repair in repair-proficient cells might result in the loss of the lesion before its mutagenic properties could be realized. Hence, the contribution of 3-MeAde to SOS dependent mutagenesis in fully repair-proficient cells was also investigated. 3 MeAde lesions were removed from MNU-treated DNA by the purified TagI protein. This prior removal of 3-MeAde had little effect on mutagenesis in SOS-induced or SOS-uninduced cells. Thus, in repair-proficient cells, 3-MeAde is efficiently removed from DNA and does not contribute in a major way to mutagenesis. These results indicate that some other A or T adduct(s) are responsible for the bulk of the mutagenesis observed under SOS-induced conditions. PMID- 1747929 TI - The effect of dose and enzyme inducers on the metabolism of 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) in rats. AB - Male Fischer 344 rats were given a single dose of 0.03-30 mg/kg of [2-14C]2-amino 1-methyl-6-phenylimidazo[4,5-b]pyridine ([14C]PhIP), the radioactivity in urine and feces was determined over 48 h, and the major metabolites were identified and quantified. Dose had little effect on the profile of metabolites in the urine but did influence the profile in the feces. PhIP was more efficiently metabolized at higher doses. In addition, rats were pretreated with Aroclor 1254 (PCB), 3 methylcholanthrene (MC), phenobarbital (PB), PhIP and corn oil prior to a single dose of [14C]PhIP, and compared with a control group receiving [14C]PhIP only. The major metabolites in the urine and feces were quantitated for each group, as well as PhIP binding to serum proteins, hemoglobin and selected tissues. Pretreatment with MC and PCB resulted in an increase in the amount of 4' hydroxylation of PhIP and a decrease in the amount of N-hydroxylated metabolites in the urine. Pretreatment with PB resulted in an increase in the amount of N hydroxylated metabolites, but a decrease in 4'-hydroxylation. Pretreatment with either MC or PCB resulted in an increase in PhIP binding to the liver and kidney, while reducing the binding in other tissues. Animals pretreated with PhIP showed few significant differences from the untreated group, while pretreatment with PB in general resulted in a decrease of PhIP binding in tissues. PMID- 1747930 TI - Effects of glucose on the formation of PhIP in a model system. AB - The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl 6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees C several mutagens were produced. Identification by HPLC, UV absorption spectroscopy and mass spectrometry revealed the presence of PhIP as well as 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline and minor amounts of 2-amino-3,4,8 trimethylimidazo[4,5-f]quinoxaline. Heating the system without glucose produced PhIP as a single mutagen, but in considerably lower amount. An inhibiting effect of glucose in high concentrations was demonstrated. When glucose was added in more than or equimolar amounts of the other two reactants, the formation of mutagens was markedly reduced. Tyrosine heated under the same conditions, with creatine and glucose, showed mutagenic activity. However, no PhIP nor any other known food mutagen was identified from the tyrosine mixture. PMID- 1747931 TI - Antiproliferative effects of the Ca2+/calmodulin antagonist B859-35 and the Ca(2+)-channel blocker verapamil on human lung cancer cell lines. AB - We have recently demonstrated that the dihydropyridine-derivative B859-35 has a selective chemotherapeutic effect on experimentally induced neuroendocrine lung tumors in hamsters. These tumors resembled human atypical lung carcinoids morphologically and expressed mammalian bombesin, calcitonin and neuron-specific enolase. In the hamster model, B859-35 had no antiproliferative effect on pulmonary adenomas of Clara cell origin. In this study, we have tested the antiproliferative effects of B859-35 and of the Ca(2+)-channel blocker Verapamil in vitro on three human lung cancer cell lines. The neuroendocrine cell line NCI H727 is derived from a lung carcinoid and expresses mammalian bombesin and calcitonin. Two non-neuroendocrine cell lines are derived from peripheral pulmonary adenocarcinomas, with line NCI-H322 expressing features of Clara cells while line NCI-H358 expresses features of alveolar type II cells. B859-35 was a potent antiproliferative agent in the neuroendocrine line NCI-H727 at concentrations as low as 0.001 pM, while it inhibited cell proliferation in the two other cell lines at concentrations of 100 nM and above. Verapamil inhibited cell proliferation in the neuroendocrine line NCI-H727 at concentrations of 1 nM and above. PMID- 1747932 TI - Comparison of the inactivation of mammalian and bacterial O6-alkylguanine-DNA alkyltransferases by O6-benzylguanine and O6-methylguanine. AB - The inactivation of human and Escherichia coli O6-alkylguanine-DNA alkyltransferase by O6-methylguanine and O6-benzylguanine was compared. When HT29 cell extracts or E. coli Ada protein were incubated in the presence of 200 microM O6-methylguanine for 1 h, alkyltransferase activity was reduced to 44 and 39% of control levels respectively. However, under the same conditions O6-benzylguanine completely depleted alkyltransferase activity in the extract from human cells but had virtually no effect on the Ada protein. Incubation of the HT29 cell alkyltransferase with O6-benzyl[3H]guanine resulted in a time-dependent production of [3H]guanine. No similar production of [3H]guanine was observed in the presence of the Ada protein. In CHO cells transfected with the bacterial ada gene (CHO-ada) or the human alkyltransferase cDNA (CHO-MGMT), treatment with 500 microM O6-methylguanine inhibited both alkyltransferases by greater than 85%. In contrast, 2 microM O6-benzylguanine inhibited human alkyltransferase expressed in CHO-MGMT cells by greater than 99% though concentrations as high as 25 microM for 24 h had no inhibitory effects on the bacterial alkyltransferase expressed in CHO ada cells. This selective inhibition was also observed in vivo in transgenic mice expressing ada in the liver where O6-benzylguanine caused a decrease of only 40% in total hepatic alkyltransferase activity compared to 95% in non-transgenic mice, consistent with inhibition of only the mammalian alkyltransferase and maintenance of bacterial alkyltransferase activity in these animals. Thus, while O6-methylguanine at high concentrations inactivates both bacterial and mammalian alkyltransferases, O6-benzylguanine is a substrate only for the mammalian protein and is unable, perhaps due to steric hindrance, to inhibit the Ada protein. PMID- 1747933 TI - Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents. AB - Carcinogen-induced aberrant crypts (AC) of the colon are a precancerous state that leads to malignancy. The inhibition of AC formation by chemopreventive agents was evaluated in this study. Colon AC were induced by 1,2 dimethylhydrazine (DMH) in 3 weeks in CF1 mice. The cecum of the large intestine of CF1 mice did not produce more than one AC focus per animal. The effect of DMH and that of the inhibitors in this part of the large bowel were essentially similar to the vehicle control and inhibitor-only controls. The response of DMH treatment in the colorectal portion of the large bowel was found to be different from that of the cecum. The DMH treated mice had 13-17 foci per animal in three different experiments. The average number of AC per focus was greater than one in all three experiments performed. None of the inhibitor-only control animals nor the cottonseed oil vehicle control animals developed AC focus in the colorectal or the cecal part of the large bowel. The known inhibitor of colon carcinogenesis 3-butyl-4-hydroxyanisole reduced DMH-induced average AC formation by 10 and 46% at 1 and 4 mg per dose, respectively. The inhibitors 2-n-butylthiophene and phenylpropylisothiocyanate reduced DMH-induced average AC formation greater than 34 and greater than 40% respectively. The postulated inhibitor 2-n octylthiophene, which is an eight-carbon homolog of 2-n-butylthiophene, similarly reduced DMH-induced AC formation. The known colon carcinogenesis inhibitor dehydroepiandrosterone, in contrast, has no effect. The inactivity of dehydroepiandrosterone to inhibit colon AC formation was attributed to its mechanism of inhibitory action, which differs from that of the phenol, isothiocyanate and thiophenes. The short duration that is required to produce quantifiable results suggests that the reduction of carcinogen-induced AC formation may be developed into a useful prescreening assay for potential chemopreventive agents against colon cancer. PMID- 1747934 TI - S9-mediated metabolism of 1-nitropyrene to a mutagen in Chinese hamster ovary cells by ring-oxidation under aerobic conditions and by nitroreduction under anaerobic conditions. AB - Both nitroreduction and ring-oxidation appear to be important pathways for the in vivo metabolic activation of 1-nitropyrene (1-NP), a tumorigenic environmental contaminant. Previous studies, however, suggest that ring-oxidation is primarily responsible for the S9-mediated mutagenicity of 1-NP in Chinese hamster ovary (CHO) cells. In this study, an anaerobic rat liver S9 metabolizing system was used to facilitate the nitroreduction of 1-NP to a mutagen in repair-proficient CHO-K1-BH4 cells and excision-repair-deficient CHO-UV5 cells, and results using this system were compared with those obtained from the aerobic S9 metabolism of 1 NP. Anaerobic S9 metabolism of 2.5-15 micrograms/ml of 1-NP produced 15 +/- 3 mutants/10(6) cells/microgram 1-NP/ml with CHO-UV5 cells and 3 +/- 1 mutants/10(6) cells/microgram 1-NP/ml with CHO-K1-BH4 cells (different at P less than 0.001). When the assays were conducted with CHO-K1-BH4 cells, the number of mutants produced by 1-NP using aerobic treatment conditions was similar to that found using anaerobic conditions. In contrast, the aerobic incubations resulted in significantly fewer 1-NP-induced mutants than the anaerobic treatments when the assays were conducted with CHO-UV5 cells. Examination of the metabolites produced during these incubations indicated that under anaerobic conditions 1-NP was efficiently converted to 1-aminopyrene, while aerobic metabolism resulted in the formation of 1-NP phenols and dihydrodiols. DNA adduct analysis by 32P postlabeling revealed that 1-NP treatment using the anaerobic procedure produced CHO-cell adducts by the reduction of 1-NP to N-hydroxy-1-aminopyrene, while aerobic incubations resulted in adducts produced by other metabolic pathways, probably involving ring-oxidation. These findings indicate that the S9-mediated metabolism of 1-NP under anaerobic conditions produces mutations and DNA adducts in CHO cells that are the result of nitroreductive metabolism. The results with aerobic S9 metabolism were consistent with the previous conclusion that this system mediated the mutagenicity of 1-NP in CHO cells mainly through the generation of ring-oxidized metabolites. The combination of the anaerobic and aerobic S9 metabolism procedures provides a new approach for evaluating the mutagenicity of nitropolycyclic aromatic hydrocarbons in mammalian cells. PMID- 1747935 TI - All-trans retinoic acid protects against conversion of chemically induced and ultraviolet B radiation-induced skin papillomas to carcinomas. AB - It is becoming increasingly clear that cutaneous carcinogenesis in murine skin is a stepwise process comprising of initiation, promotion and progression. Most of the papillomas induced by an initiation-promotion protocol regress, while a few of them progress to malignant carcinomas. Progression of benign tumors into malignant cancer is critical since the latter lesions are capable of metastatic spread and eventual death. Inhibitors of the conversion process are therefore likely to be useful as cancer chemopreventive agents. All-trans retinoic acid (RA) is a known regulator of cellular proliferation and differentiation, and a known inhibitor of tumor promotion in murine skin. In this study we assessed the effect of topical application of RA on conversion of benign skin papillomas to malignant carcinomas. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) as tumor initiator followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter. In SKH-1 hairless mice papillomas were induced by thrice weekly exposure to ultraviolet B (UVB) radiation. At 18 (DMBA/TPA group) and 25 (UVB group) weeks papilloma yield stabilized and no new tumors developed. Beginning at the 20th week (DMBA/TPA group) and at the 27th week (UVB group), malignant conversion was achieved by twice weekly topical application of TPA or free radical-generating compounds benzoyl peroxide (BPO), 2,2-azobis(2-amidinopropane) (ABP) and tert-butyl peroxybenzoate (BPB). Application of RA (10 micrograms/animal) 1 h prior to skin application of TPA, BPO, ABP or BPB afforded significant protection (up to 70%) only against malignant conversion mediated by free radical-generating compounds in both chemically induced and UVB-induced benign skin papillomas. On the other hand, preapplication of RA was less effective in the suppression of spontaneous malignant conversion in vehicle-treated animals. These results suggest that, in addition to their anti-tumor promoting effects, retinoids may also act as anti carcinogens by inhibiting the process of malignant conversion induced by free radical-generating compounds. PMID- 1747936 TI - Analysis of the Ha-ras oncogene in C3H/He mouse liver tumours derived spontaneously or induced with diethylnitrosamine or phenobarbitone. AB - In a study of the mechanisms involved in the induction of tumours by chemicals, the Ha-ras oncogene was analysed in liver tumours induced by the genotoxic carcinogen diethylnitrosamine (DEN), or the non-genotoxic agent phenobarbitone (PB) in C3H/He mice. Mutations were detected using the polymerase chain reaction and oligonucleotide hybridization. Codon 61 mutations were detected in 41% of DEN induced tumours (19/46), either in the first base (CG----AT, 12/19), a transversion, or the second base (AT----GC, 7/19), a transition. Codon 61 mutations were also found in 29% of spontaneous tumours (all CG----AT, 6/21) but none were detected in PB-induced tumours (0/15) or in normal liver tissue of untreated mice (0/30). No mutations were detected at codon 12. Low and variable expression of the Ha-ras gene was detected in all liver tissues with moderately raised levels (175-200%) in spontaneous, DEN and PB-induced tumours as compared to normal liver tissue. The H-ras gene was methylated to some extent in all liver tissues, with no discernible difference between the treatments. The frequency of the Ha-ras mutation at codon 61 in DEN-induced tumours is greater than in spontaneously arising tumours. This increase is not accompanied by any specific alteration in the expression or methylation of the gene. Since PB-induced tumours do not possess mutations in the Ha-ras gene at codons 12 or 61, the data suggest that the non-genotoxic agent PB induces tumours in the C3H/He mouse liver with a mechanism distinct from that of spontaneous tumours or those that result from treatment with a potent genotoxic carcinogen such as DEN. PMID- 1747937 TI - Assessment of the antioxidant/prooxidant status of murine skin following topical treatment with 12-O-tetradecanoylphorbol-13-acetate and throughout the ontogeny of skin cancer. Part I: Quantitation of superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase. AB - The activities of several enzymes involved in reactive oxygen production and detoxification were quantified in murine skin during the ontogeny of chemically induced skin cancer. Relative to solvent-treated controls, the specific activities of epidermal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were reduced approximately 45, approximately 60 and approximately 24% respectively, 24 h after the fourth or tenth topical application of 1 microgram of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of SENCAR mice. The specific activity of epidermal xanthine oxidase (XO) increased approximately 350% during the same period. SOD and CAT specific activities in papillomas and carcinomas generated in an initiation-promotion protocol were approximately 15 and approximately 40% respectively of the activities measured in age-matched, non-treated mice. CAT and SOD activities were also significantly suppressed in the skin adjacent to the papillomas for several weeks following the cessation of TPA promotion, but eventually recovered to the levels measured in age-matched controls. XO specific activities in papillomas and squamous cell carcinomas (SCC) were approximately 85-350% greater than the activities determined in skin adjacent to the tumors. The increases in XO and the decreases in SOD and CAT activities measured in the tumors were independent of continued treatment with TPA, and thus characteristic of the tumor phenotype. GPX activities in papillomas were comparable to normal, untreated skin, but reduced approximately 22-41% in SCC. Collectively, these studies demonstrate that TPA orchestrates changes in the activities of several enzymes involved in reactive oxygen metabolism that are characteristic of the papilloma and SCC phenotype. PMID- 1747938 TI - Assessment of the antioxidant/prooxidant status of murine skin following topical treatment with 12-O-tetradecanoylphorbol-13-acetate and throughout the ontogeny of skin cancer. Part II: Quantitation of glutathione and glutathione disulfide. AB - Tissue glutathione (GSH) and glutathione disulfide (GSSG) contents were quantitated in the skins of female SENCAR mice following the topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), and in the skin tumors generated by an initiation-promotion protocol. Total epidermal GSHt (GSH + GSSG) and GSSG contents were not reproducibly and significantly altered 0.5, 4 or 24 h after one or four topical applications of 1 microgram TPA, relative to the values obtained in age-matched, solvent-treated mice. Similar findings held for dermal GSHt at all times of analyses, and for dermal GSSG contents 0.5 and 4 h after TPA application. However, dermal GSSG contents were slightly elevated 24 h after TPA application. The GSHt and GSSG contents of skins initiated with 10 nmol 7,12 dimethylbenz[a]anthracene (DMBA) and harvested 17, 29 and 37 days after the cessation of chronic treatment with acetone (14 weeks, twice a week) were comparable to the values measured in age-matched, non-treated skins. In contrast, GSHt contents of papillomas harvested 17, 29 and 37 days after the cessation of chronic treatment with 1 microgram TPA (14 weeks, twice a week) were 2- to 4-fold greater than the values measured in non-treated mice, and DMBA-initiated, acetone promoted mice, and the non-tumorous tissue adjacent to the papillomas. Comparable changes did not occur in papilloma GSSG contents. GSHt contents in squamous cell carcinomas (SCC) were twice the values measured in papillomas and 5- to 8-fold greater than the values measured in non-treated skins, and the non-tumorous tissue adjacent to SCC. Similarly, GSSG contents in SCC were elevated multifold relative to papillomas, non-treated skin and the non-tumorous tissue adjacent to SCC. Epidermal cell suspensions prepared by the trypsin-flotation procedure retained less than 2% of their original GSHt content and had reduced GSHt/GSSG ratios. Collectively these studies suggest that (i) if promoting doses of TPA induce oxidative stress in murine epidermis, it cannot be detected by measurements of GSH/GSSG; (ii) the antioxidant capacity of epidermal cells prepared by the trypsin-flotation procedure is severely compromised; and (iii) GSHt contents progressively increase during skin tumor ontogeny. PMID- 1747939 TI - Immunochemical localization and functional characterization of cytochrome P450IIE1 in rat hepatocyte foci and nodules. AB - P450IIE1 was studied in rat hepatocyte foci and nodules from male Wistar rats, treated for 7 weeks with N-nitroso-morpholine (20, 40 and 80 mg/ml of drinking water). Livers were examined after 15, 23 and 31 weeks. Using specific anti P450IIE1 IgG, different phenotypes of P450IIE1-altered foci were observed: (i) positive foci, predominant at early times and at the two lower dosages, (ii) negative foci and (iii) mixed-type foci consisting of P450IIE1-positive and negative hepatocytes which were preponderant at 31 weeks. Immunoblotting of microsomes from livers containing foci and nodules obtained at week 31 of the experiment revealed a decrease in P450IIE1 level, which was correlated to decreased high affinity dimethylnitrosamine demethylase activity. The results suggest phenotypic heterogeneity of P450IIE1-altered foci with predominantly negative foci at later stages. PMID- 1747940 TI - Characterization of the mouse homolog of the XPBC/ERCC-3 gene implicated in xeroderma pigmentosum and Cockayne's syndrome. AB - The human XPBC/ERCC-3 DNA repair gene specifically corrects the repair defect of xeroderma pigmentosum (XP) complementation group B and rodent repair mutant cell lines of group 3. The gene encodes a presumed DNA- and chromatin-binding helicase involved in early steps of the excision repair pathway. To study the evolution of this gene, its expression in different tissues and stages of development and to permit the generation of a mouse model of XP by targeted gene replacement in mouse embryonal stem cells, we have isolated the mouse XPBC/ERCC-3 homolog. Sequence comparison of the predicted protein revealed a 96% amino acid identity with the human gene product. Notably, all postulated functional domains were strictly conserved. The mouse XPBC/ERCC-3 promoter is--like its human counterpart -devoid of classical promoter elements such as TATA and CAAT boxes and contains several conserved segments with unknown function. One of these conserved regions, consisting in part of a polypyrimidine track, is also present in the ERCC-1 promoter. The mouse XPBC/ERCC-3 gene is expressed constitutively at low levels in all tissues examined except for testis, where its expression is significantly enhanced. PMID- 1747941 TI - Incidence of Harvey ras oncogene point mutations and their expression in methylbenzylnitrosamine-induced esophageal tumorigenesis. AB - Activation of the ras oncogene was investigated in esophageal tumors induced by methylbenzylnitrosamine (MBN) in the Sprague-Dawley rat. DNA was extracted from grossly visible carcinogen-induced tumors. H-ras and K-ras gene sequences were then amplified by the polymerase chain reaction. Point mutations in the ras genes were then identified by selective hybridization to allele-specific oligonucleotide probes. A guanine to adenine transition at the 35th nucleotide in the H-ras coding sequence (GGA to GAA in the 12 codon) was observed in 67% (10 of 15) of the papillomas examined. This mutation codes for glutamate instead of glycine as the 12th amino acid of the ras p21 protein. No other H-ras or K-ras mutations were observed. To determine the distribution of this H-ras mutation in esophageal tissues, histological sections of MBN-treated esophagi were stained with a monoclonal antibody (E184) which selectively recognizes the mutated ras p 21 with glutamate substituted for glycine as the 12th amino acid. Expression of the mutant ras p21 protein was observed in 20% of the squamous papillomas, 13.6% of hyperplastic lesions and 10% of dysplastic lesions. Thus, activation of the H ras oncogene as a result of guanine to adenine point mutation is a frequent event in esophageal tumors induced by MBN, occurring in 67% of squamous papillomas, but expression of the corresponding mutant ras p21 protein is observed in a much smaller proportion of the tumors in this animal model. PMID- 1747942 TI - Comparative metabolism of 7,12-dimethylbenz[a]anthracene by the perfused liver and liver microsomal preparations from Sprague-Dawley rats. AB - The metabolism of DMBA by microsomes and various cell cultures has been widely studied. However, the biotransformation of this compound by intact organs has not been well characterized. In order to compare the metabolism of DMBA in the whole liver with that in subcellular preparations, we used an in situ single-pass rat liver perfusion system and rat liver microsomes. [14C]DMBA was infused into the livers of Sprague-Dawley rats during the first 60 min of a 120 min perfusion. HPLC analysis of extracts of perfusate samples indicated that DMBA was rapidly oxidized in this system to a series of metabolites. The major products were polar metabolites including the trans-5,6- and the trans-10,11-dihydrodiols (46%), the trans-3,4-dihydrodiol (5%) and the 7-OHM-12-MBA and the 12-OHM-7-MBA metabolites (12%) of DMBA. Microsomes prepared from livers of corn oil treated rats were incubated with [14C]DMBA for 60 min, then extracted. In the microsomal system the major DMBA metabolites were the trans-8,9-dihydrodiol (6%), the 7- and 12 hydroxymethyl (20%), and the 3- and 4-hydroxy (11%) of DMBA with the more polar metabolites and the trans-3,4-dihydrodiol present at lower levels (12 and 3% respectively). This is the first report of DMBA metabolism in a whole liver preparation and the results are clearly different from those obtained in subcellular preparations in our laboratory and in cell culture systems elsewhere. These results have important implications for understanding DMBA biotransformation in vivo. PMID- 1747943 TI - Immunohistochemical localization of glutathione S-transferases alpha, mu, and pi in normal tissue and carcinomas from human colon. AB - Analysis of the heterogeneity of glutathione S-transferase (GST) isozyme expression was carried out by immunohistochemical evaluation of human colon biopsy tissue from 30 patients. Using polyclonal antibodies specific for the GST alpha, mu and pi families of isozymes, an increased expression of pi was found in 21/30 carcinoma specimens compared to their pair-matched controls. This isozyme was the most prevalent in all colon samples. GST mu was expressed at reduced levels in 20/30 carcinoma specimens when compared to normal. GST alpha showed no consistent change. Analysis of the immunostaining in different cell types showed that the highest intensity stain for all isozymes was in the columnar epithelial cells. These cells were primarily responsible for the proportional changes in GST pi and mu between carcinoma and normal tissues. In addition, goblet (crypt), endothelial and muscle cells stained positively. In the lamina propria, lymphocytes and phagocytes stained positively, while fibroblasts, plasma cells and leukocytes were negative. Endocrine cells were also negative. The differential expression of GST pi and mu, confirming biochemical data, supports the potential utility of GST pi as a carcinoma marker. PMID- 1747944 TI - Specific reduction of I-compound levels in DNA from spontaneous hepatomas of 22 24 month old male C3H mice. AB - As previously shown by 32P-postlabeling, I-compound levels are reduced in target tissue DNA of animals exposed to one of several non-genotoxic hepatocarcinogens, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin, carbon tetrachloride, peroxisome proliferators and choline-devoid diet. I-compound levels are further reduced, sometimes to undetectable levels, in chemically induced, transplantable rat (Morris) hepatomas and hepatocellular carcinomas induced by peroxisome proliferators or choline-devoid diet. The current study investigated I-compounds in spontaneous hepatic adenomas of genetically susceptible male C3H mice. DNA samples from individual tumors, background livers (non-tumor bearing lobe from tumor bearing mouse) and non-tumor bearing normal livers taken from 22-24 month old animals were analyzed by 32P-postlabeling. I-compound profiles were qualitatively comparable among the three types of tissues. However, levels of most I-compounds were 2.6-5.0 times lower in tumors than in background liver and non-tumor bearing normal liver. There were virtually no differences between background liver and normal liver. Taken together with the previously reported I compound deficiency in carcinogen-induced hepatomas, the present observations on genetically initiated neoplasms suggest that this phenomenon may play a role in hepatocarcinogenesis and maintenance of neoplasia. PMID- 1747945 TI - Autoimmunity to a 28-30 kD cell membrane DNA binding protein: occurrence in selected sera from patients with SLE and mixed connective tissue disease (MCTD). AB - Previous experiments have established the presence of a 30-kD DNA binding protein on the surface of human leukocytes. Herein we report that selected sera from patients with systemic lupus erythematosus (SLE) and MCTD are reactive with a 28 30 kD protein on immunoblots of peripheral blood mononuclear cells (PBMC) cell membrane preparations; the reactivity is abolished by prior incubation of the blot with DNA. Antibodies eluted from the 28-30 kD strip inhibited the binding of 3H. DNA to human PBMC. An immunomatrix of 28-30 kD reactive immunoglobulins was able to extract a 29-kD DNA binding protein from a PBMC cell membrane preparation. Flow cytometry experiments confirmed the cell surface IgG reactivity of sera with T lymphocytes. Additional experiments indicated that cell surface IgG binding was not due to antibodies binding to cell surface DNA, DNA anti-DNA immune complexes reacting with a DNA binding protein, anti-histone antibodies or anti-Sm antibodies. It is hypothesized that this autoimmune response could be one component of an idiotypic network involving anti-DNA antibodies. PMID- 1747946 TI - Transforming growth factor-beta 1 in rheumatoid synovial membrane and cartilage/pannus junction. AB - Transforming growth factor (TGF)-beta has been shown to promote tissue repair and have immunosuppressive actions, and has been proposed to have a role in rheumatoid arthritis (RA). Using immunohistochemical techniques with rabbit F(ab')2 antibodies raised against recombinant human TGF-beta 1, we have detected TGF-beta 1 in the synovial tissue and cartilage/pannus junction (CPJ) from 18/18 patients with RA. TGF-beta 1 was found predominantly in the thickened synovial lining layer in RA, but also detected in a perivascular pattern in the synovial interstitium as well as in occasional cells in the lymphoid aggregates. At the CPJ it was found both in cells at the distinct junction as well as in the transitional region of the diffuse fibroblastic zone. The cells staining for TGF beta 1 were identified by double immunofluorescence staining as being from the monocyte/macrophage series as well as the type B synovial lining cells. TGF-beta 1 was also detected in the synovial membrane sections from 4/4 patients with systemic lupus erythematosus/mixed connective tissue disease and 5/8 patients with osteoarthritis, in a similar distribution to that seen in RA, and in the lining layer of 1/7 normal synovial membranes. These results add to histological evidence confirming that TGF-beta 1 is present in RA synovial cells and those from other arthritides. The distributions of TGF-beta 1 in RA synovial membrane reflects its known actions, as it can be detected at the CPJ, where it could induce repair, and close to activated cells upon which it may exert an immunosuppressive action. PMID- 1747947 TI - Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory arthropathies using biotinylated oligonucleotide probes in situ. AB - A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA, PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies. PMID- 1747948 TI - Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix. AB - Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens. PMID- 1747949 TI - Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice. AB - We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-alpha), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon gamma (IFN-gamma) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P less than 0.01) and in mice treated with control serum (P less than 0.02). This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK 432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P less than 0.01) and surface-Ig+ (S-Ig+) cells increased (P less than 0.05), whereas the proliferative response of spleen cells to concanavalin A (P less than 0.01) and lipopolysaccharide (P less than 0.05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF. PMID- 1747950 TI - Regulation of experimental autoimmune uveitis in rats--separation of MHC and non MHC gene effects. AB - Experimental autoimmune uveitis (EAU) is an organ-specific autoimmune disease and has served as a model of certain ocular inflammatory conditions in man. The present study was aimed at separating the effects of MHC and non-MHC genes on the development of EAU in the rat. EAU-susceptible LEW (RT1l), EAU-resistant WKAH (RT1k), and WKAH.1L (RT1l) MHC congenic strain of WKAH background rats were immunized with retinal soluble antigen (S-Ag) in Freund's complete adjuvant (FCA). LEW rats showed typical EAU, while neither WKAH nor WKAH.1L congenic rats developed EAU. However, when an additional i.v. injection of Bordetella pertussis was given, all rat strains developed EAU. Furthermore, when immunized with peptide M, an 18-mer synthetic peptide, which corresponds to amino acid positions 303-320 of bovine S-Ag, and given an additional i.v. injection of B. pertussis, LEW and WKAH.1L rats developed EAU, whereas WKAH did not. When ACI (RT1avl), BUF (RT1b), LEJ (RT1j), W (RT1k), F344 (RT1lvl), BN (RT1n), NIG-III (RT1q), TO (RT1t), and SDJ (RT1u) rats were immunized with peptide M or S-Ag and then B. pertussis, all strains developed EAU by immunization with S-Ag plus B. pertussis, but only F344 and NIG-III developed EAU by immunization with peptide M. These findings suggest that susceptibility to EAU in rats is controlled by both MHC and non-MHC genes; and that in the absence of B. pertussis adjuvant, the form of disease induced by native S-Ag in FCA is governed by non-MHC gene(s). However, this effect of non-MHC gene(s) could no longer be observed when the rats were also injected with B. pertussis adjuvant at sensitization. PMID- 1747951 TI - Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis. AB - Characterization of in vitro lymphocyte responsiveness was performed on selected groups of onchocerciasis patients from Sudan and Sierra Leone. These patients manifested a very broad range of clinical signs and showed widely divergent parasite infection intensities. Lymphocyte proliferative responses to soluble Onchocerca volvulus antigen (sAg) were poor in infected persons; mitogen and PPD responses were maintained in the normal range in one group of patients from southwestern Sudan, but were profoundly depressed in a group from N.E. Sudan. Proliferative responses and interferon-gamma (INF-gamma) secretion were very significantly depressed in the presence of live microfilariae of O. volvulus or secretions/excretions (S/E) from microfilariae (mf) or from female, but not male, adult parasites. Lymphocyte responses were maintained near normal when exogenous IL-2 was added to these cultures. The results indicate that O. volvulus infection and its clinical consequences are not consistently associated with systemic deficits in immune responsiveness. However, suppression of lymphocyte reactivity by mf and S/E in vitro suggests that direct parasite intervention in host cell responses could be taking place in vivo, perhaps at the local microenvironment level; mediated by effects on cytokine production. PMID- 1747952 TI - Contact sensitivity in the murine oral mucosa. I. An experimental model of delayed-type hypersensitivity reactions at mucosal surfaces. AB - We have examined in a murine model, the potential of the oral mucosa (OM) to serve as inductive and/or expression site(s) of delayed-type hypersensitivity (DTH) reactions. The expression of DTH reactions in the murine buccal mucosa was studied after topical application of oxazolone or picryl chloride onto the OM of animals previously sensitized with either hapten. Irrespective of the site of priming (skin or buccal mucosa), inflammatory cells appeared in the OM following buccal elicitation with the pertinent hapten. The density of infiltrating cells peaked at 24 h after hapten elicitation. Such inflammatory reactions, which comprised mainly mononuclear cells at 24 h, were preceded by an early inflammatory reaction that developed only in animals previously sensitized at skin sites. This early reaction, comprising mainly PMN neutrophils, peaked at 6-8 h, declined by 8-16 h, and was not observed in mice previously sensitized in the buccal mucosa. The 24 h reactions failed to develop in nude mice similarly treated, in intact unsensitized mice, as well as in animals sensitized with an irrelevant hapten. These reactions could be adoptively transferred to naive animals by LN cells but not by serum from sensitized syngeneic donors. Furthermore, LN cell suspensions depleted of T cells failed to transfer sensitization for subsequent OM DTH. Topical application of contact sensitizing haptens onto OM induced priming for subsequent DTH reactions elicited with recall antigen applied at a distant skin site or at a local buccal site. These results demonstrate that the OM has the capacity to serve both as an inductive and as an expression site for T cell-mediated inflammatory reactions, be these expressed or induced at local mucosal sites or at remote systemic (skin) sites. This animal model should be valuable for studying the regulation of T cell-mediated inflammatory responses at mucosal surfaces. PMID- 1747953 TI - Restricted specificity of the autoantibody response in Goodpasture's syndrome demonstrated by two-dimensional western blotting. AB - The autoantigen in Goodpasture's syndrome is known to be contained within the non collagenous (NC1) domain of type IV collagen. We have examined the specificity of autoantibodies to glomerular basement membrane (GBM) using the technique of 2-D electrophoresis followed by Western blotting. Protein stains of 2-D gels of collagenase-digested human GBM revealed extensive charge and size heterogeneity. Major components were of mol. wt 24-30 kD and 43-56 kD, corresponding to monomeric and dimeric subunits of NCl. Western blotting of 2-D gels with IgG from patients with anti-GBM disease demonstrated that the most antigenic components migrated as cationic 28-kD monomers (pI 10) and similarly charged dimers, although other components were recognized less strongly. The mobility of the strongly antigenic polypeptides was different to that of the known alpha 1 and alpha 2 chains of type IV collagen. Autoantibodies from all 20 patients studied showed the same pattern of reactivity, regardless of their clinical features (in particular, the presence or absence of pulmonary haemorrhage) or HLA type. A monoclonal antibody (P1) to human GBM bound in a similar pattern, particularly recognizing the cationic components. 2-D gels of affinity-purified GBM from a P1 column showed enrichment of the 28-kD monomers, which were recognized by human autoantibodies on Western blotting. These results demonstrate that the autoimmune response in Goodpasture's syndrome is of restricted specificity, and support the suggestion that the major autoantigenic determinant is present on the novel alpha 3 chain of type IV collagen. PMID- 1747954 TI - Vascular deposition of complement-split products in kidney allografts with cell mediated rejection. AB - Complement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidase staining using MoAbs reactive with complement-split products. Intense deposition of complement fragments C4d and C3d in peritubular capillaries, indicating activation of the classical pathway, could be detected in the majority of transplanted kidneys with cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biopsies from patients with high 'immunological risk' (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paucity of immunoglobulins in transplant biopsies, antibodies directed against endothelial cell antigens should be considered as a possible cause of classical complement activation. PMID- 1747955 TI - Surface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing 'charge-hybrid' molecules. AB - The deposition of antigens and immune complexes (IC) in the renal glomerulus is charge-dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly-L-lysine chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human serum albumin (HSA]. Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly-L-lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA:poly-L-lysine to be a function of the number of lysine residues; binding of HSA:poly-L-lysine20 was 2.5 times higher than HSA:poly-L-lysine17 (P less than 0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly-L-lysine by 75%, indicating the charge-based nature of the interaction. HSA:poly-L-lysine20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly L-lysine followed by anti-HSA antibody induced immune complex formation in the capillary wall, giving rise to a granular immunofluorescence pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis. PMID- 1747956 TI - Autoantibodies against Forssman glycolipids in Graves' disease and Hashimoto's thyroiditis. AB - Sera from patients with Graves' disease and Hashimoto's thyroiditis have been shown to react with the Forssman glycolipid antigen (Gb5) using the techniques of high performance thin-layer chromatography (HPTLC) immunostaining and ELISA. Human monoclonal antibodies (MoAbs) have been prepared by fusion of human myeloma with peripheral lymphocytes from patients with Graves' disease. A MoAb, TRMo-4, reacted strongly and specifically with Gb5. These results suggest that anti Forssman antibody may be involved in the pathogenesis of these autoimmune diseases. The detection of anti-Forssman glycolipid antibody may provide a useful means for clinical diagnosis and therapy. PMID- 1747957 TI - Normal and sarcoid alveolar macrophages differ in their ability to present antigen and to cluster with autologous lymphocytes. AB - Human bronchoalveolar macrophages from normal individuals function poorly as accessory cells for the presentation of common recall antigens. In sarcoidosis, alveolar macrophages (AM) are reported to be effective accessory cells for the presentation of such antigens. In this study normal and sarcoid AM were compared with blood monocytes for their ability to act as accessory cells in presenting tuberculin purified protein derivative (PPD) and streptokinase-streptodornase (SKSD) to autologous T lymphocytes, or to form spontaneous, antigen- or mitogen induced clusters with the T cells. When compared to autologous monocytes, normal AM failed to present the two recall antigens effectively. Likewise normal AM formed very few clusters with T lymphocytes when compared to monocytes, even in the presence of antigens or the mitogen phytohaemagglutinin (PHA). In contrast, sarcoid AM presented both antigens as effectively, and were equally effective as monocytes in forming clusters with T lymphocytes, spontaneously and in further response to antigen or mitogen. The results suggest that in sarcoidosis enhanced accessory cell function and enhanced cluster formation may be related features of bronchoalveolar macrophage populations. PMID- 1747958 TI - Cytotoxicity against human peripheral blood mononuclear cells and T cell lines mediated by anti-T cell immunotoxins in the absence of added potentiator. AB - Several in vitro assays have indicated that anti-T cell immunotoxins (IT), composed of monoclonal antibodies (MoAbs) conjugated to ricin A chain (RTA), are maximally effective against T cells only in the presence of potentiators. It was thought that such IT might not be sufficiently cytotoxic to deplete T cells in vivo upon administration to patients. Therefore, we have re-evaluated the in vitro assays and report herein that even with a short exposure time (2 h), the two anti-T cell IT, H65-RTA (anti-CD5 MoAb coupled to RTA) and 4MRTA (anti-CD7 MoAb coupled to RTA30), were specifically cytotoxic for peripheral blood mononuclear cells (PBMC) in the absence of potentiators. Moreover, as has been reported for IT when tested against T cell lines, prolonging the exposure time of the IT with PBMC from 2 h to as long as 90 h, without added potentiators, enhanced their cytotoxicity from 2- to 40-fold. In contrast, most T cell lines were more sensitive to IT in the presence of potentiator, and IT cytotoxicity was much less enhanced by prolonging the exposure time. Thus, T cell lines may not serve as accurate models to determine the efficacy of IT against PBMC in vitro or in vivo. We conclude that IT-induced cytotoxicity of PBMC can be demonstrated in vitro at pharmacologically achievable concentrations in the absence of added potentiators. PMID- 1747959 TI - Immunochemical characterization of human antibodies to lymphoblastoid interferon. AB - Antibodies produced in recurrent respiratory papillomatosis (RRP) patients treated with lymphoblastoid interferon (lyIFN) may neutralize antiviral activity or may only bind to lyIFN. These antibodies were characterized for immunoglobulin class, IgG subclass, and light chain type by an indirect immunoassay. Serum dilutions were incubated on lyIFN-coated plates and the presence of antibody detected using peroxidase-conjugated goat antibodies to each human immunoglobulin class and light chain isotype, or using MoAbs to each human IgG subclass. Neutralizing activity was measured as the inhibition of lyIFN antiviral activity for Vervet monkey cells challenged with Semliki Forest Virus. Among antibody positive patients, 12% produced IgM coincident with IgG, and 25% produced IgA coincident with IgG. Thus, antibody responses in patients treated with lyIFN are not exclusively of IgG class. The predominant lyIFN-specific subclasses were IgG1 and IgG3, which occurred in 70% and 83% of patients, respectively. An IgG4 response was detected in two patients who also had antibody of other isotypes; no IgG2 antibody was detected in any patient. Antibodies were not IgG subclass restricted, a trend which was more pronounced in patients having neutralizing antibody than non-neutralizing antibody. Light chain molecules of lyIFN-specific antibody were of both kappa and lambda isotypes, with kappa chains occurring most frequently. Among patients having non-neutralizing antibodies, monotypic light chains occurred in 65% of the patients, whereas no patient with neutralizing antibody had monotypic light chain antibody. Sera from 599 normal human volunteers were assayed for antibody, and seven were found to be immunoreactive to lyIFN. Only one serum of the seven was positive for neutralizing activity. PMID- 1747960 TI - Inhibition of immune reactions in vivo by liposome associated transforming growth factor (TGF) type beta 1. AB - In view of its potent inhibitory capacity on immune cells in culture, we wished to determine the ability of transforming growth factor (TGF) beta 1 to down regulate immune responses in vivo. Preliminary experiments suggested that, at the doses used, systemic injection of soluble TGF beta 1 could not affect bacterial induced spleen enlargement in mice. Therefore, we sought to utilize a physiochemical property of this molecule, namely its high pI, to determine possible association between the ligand and preformed liposomes possessing an opposite charge. TGF beta 1 was preferentially associated with negatively charged, but not with neutral, liposomes. These TGF beta 1 associated liposomes were able to deliver a suppressive signal to indicator cells in vitro. Intravenous injection of TGF beta 1, associated with liposomes possessing an opposite charge, into mice immunized with heat-killed Corynebacterium parvum significantly reduced the size of the spleen as well as the number of splenocytes. Systemically administered TGF beta 1 associated liposomes could also inhibit delayed type hypersensitivity reactions to Listeria monocytogenes. These data suggest that appropriately administered, TGF beta 1 can inhibit immune responses in vivo. PMID- 1747961 TI - Extracellular organelles (prostasomes) are immunosuppressive components of human semen. AB - Numerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement that much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 microM 19 hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is still effective in inhibiting the mitogen-induced proliferation of lymphocytes. In this study such immunosuppressive activity has been separated by molecular size fractionation and the activity has been found to be particulate and corresponded to the previously reported prostasomes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of prostasomes inhibited mitogen-induced lymphoproliferation in a dose-dependent manner with a concentration of prostasomes equivalent to 40% of that seen in seminal fluid giving 69% suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely to be due to enzymatic action associated with these organelles. Interaction with the accessory cells, involved in full development of the lymphoproliferation induced by mitogen, was indicated and this possibility was supported by the demonstration of a direct effect of prostasomes on macrophage function using a mouse macrophage cell line. The prostasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenic spermatozoa the best chance of achieving fertilization, but at the same time leave the recipient open to any infection present in the semen. PMID- 1747962 TI - Transesophageal ultrasound: "invasive" noninvasive cardiology. PMID- 1747963 TI - Perspectives on therapeutic interventions in patients with acute myocardial infarction: viewpoints after the GISSI-2 results. PMID- 1747964 TI - Ambulatory blood pressure monitoring in clinical practice. AB - Ambulatory blood pressure monitoring provides a more reliable estimate of blood pressure and its diurnal variability than casual blood pressure measurement. However, the data supporting the link between cardiovascular risk and blood pressure are based almost entirely on casual, or office-based, blood pressure readings, and this form of measurement continues to be the primary factor in clinical decision making. In recent years, compelling evidence from research centers around the world has shown that ambulatory blood pressure measurements correlate more closely with the target organ complications of hypertension and predictions of future cardiovascular events than either casual office or home blood pressure measurements. Improvements in the technology have resulted in ambulatory blood pressure monitors that are increasingly accurate and unobtrusive. As evidence supporting its use continues to mount, the role of ambulatory blood pressure monitoring in clinical medicine can be expected to increase significantly. PMID- 1747965 TI - Silent myocardial ischemia after percutaneous transluminal coronary angioplasty and its prognostic significance. AB - A cohort of 175 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) were subjected to a treadmill exercise test to determine the prognostic significance of silent and symptomatic myocardial ischemia during the follow-up (average 11.7 months). The cardiac events during the follow-up were defined as cardiac death, nonfatal myocardial infarction, class III angina, and need for repeat angioplasty or coronary artery bypass surgery. During exercise, 39 patients (22%) had abnormal exercise-induced ST depression without chest pain (Group I). A group of 22 patients (13%) had both exercise-induced chest pain and ST-segment depression (Group II), and 114 patients (65%) had normal exercise test and no chest pain (Group III). The groups were similar in sex distribution, history of previous myocardial infarction, distribution of vessel disease, and presence of left ventricular dysfunction. Group III included more patients with complete revascularization. Follow-up data revealed that cardiac event rates in Groups I and II were significantly higher than in Group III (41%, 41%, vs. 16%) (p less than 0.01). The event rates in Groups I and II with multivessel angioplasty also were significantly higher than in Group III (58%, 61%, vs. 21%) (p less than 0.01). Exercise-induced silent myocardial ischemia is frequently seen early after successful PTCA and is more prevalent in patients undergoing multivessel angioplasty and incomplete revascularization. Both silent and symptomatic ischemia early after PTCA are predictors of an unfavorable prognosis. PMID- 1747966 TI - Changes in arterial levels and myocardial metabolism of catecholamines during pacing-induced angina pectoris. AB - In order to elucidate the effects of atrial pacing on cardiac catecholamine metabolism, 11 patients were studied during cardiac catheterization. Blood samples were drawn from a peripheral artery and the coronary sinus for estimation of catecholamine concentrations. Heart rate was increased by 10 beats/min each minute, and all patients experienced chest pain at maximal pacing rate. Coronary sinus blood flow rose from 122 +/- 19 at rest to 208 +/- 25 ml/min at final pacing rate, and myocardial lactate extraction ratio decreased. There was no significant change in arterial epinephrine levels, whereas the extraction ratio decreased (p less than 0.05). The norepinephrine arterial levels increased at the final pacing rate (p less than 0.01). The calculated myocardial release increased as well, but not to a statistically significant degree. The exact mechanisms of the rise in sympathetic activity and arterial norepinephrine levels cannot be ascertained with the present study design. Myocardial ischemia with subsequent chest pain seems to be a probably cause for the increased sympathetic outflow. PMID- 1747967 TI - Global and regional abnormalities of left ventricular diastolic filling in hypertrophic cardiomyopathy. AB - Left ventricular diastolic filling was studied by left ventriculography in 17 patients with hypertrophic cardiomyopathy (HCM). In 8 patients this manifested as a spadelike shape (HCM-S type) on the left ventriculogram, and in 9 patients as a banana shape (HCM-B type). Seven patients were studied as controls. Left ventricular end-diastolic pressure was higher in HCM than in controls. In HCM, peak filling rate was decreased from 1.57 +/- 0.28 of the control to 1.28 +/- 0.20 (p less than 0.05), and the time to peak filling rate was prolonged from 27 +/- 6%DT of the control to 37 +/- 7%DT (p less than 0.01). Serial volume analysis in diastole showed filling fraction was also significantly decreased to 8.2 +/- 4.1 (p less than 0.001) at the 25% diastole time and 29.6 +/- 7.2 (p less than 0.01) at half time, compared with 19.8 +/- 6.3 and 32.8 +/- 5.8 for controls, respectively. In HCM-S type, the rate of distention of left ventricular radial axes at the apical area was lower at early and mid-diastole. In HCM-B type, the rate at the basal area was lower at early and mid-diastole. Results suggest that the left ventricular diastolic filling in HCM was impaired not uniformly but regionally in the hypertrophic area at early and mid-diastole. PMID- 1747968 TI - Effects of atrioventricular block on ventricular fibrillation threshold in dog. AB - The effects of complete atrioventricular block (CAVB) on ventricular vulnerability were studied 1 week after a transcatheter electrical ablation of the AV junction in 18 closed-chest dogs. All dogs exhibited CAVB and a stable ventricular escape rhythm with a mean cycle length of 1795 +/- 600 ms. Although QT interval during CAVB was significantly prolonged compared with that during the sinus rhythm, QTc interval was significantly shortened. The ventricular fibrillation threshold was significantly elevated after creation of the block (from 9.35 +/- 2.28 to 12.3 +/- 3.69 mA, p less than 0.01). Thus, CAVB which is not associated with QTc prolongation would be even less likely to play an important role in producing ventricular fibrillation presumably including torsades de pointes or polymorphous ventricular tachycardia. PMID- 1747969 TI - The atrioventricular plane displacement as a means of evaluating left ventricular systolic function in acute myocardial infarction. AB - Displacement of the atrioventricular (AV) plane toward the cardiac apex in systole was studied quantitatively by echocardiography in 37 patients with first time acute myocardial infarction (MI) in order to evaluate left ventricular systolic function. The amplitude of AV plane displacement was recorded from the apex at four different sites corresponding to the septal, lateral, anterior, and posterior walls of the left ventricle from apical 4- and 2-chamber views. The patients had a decreased displacement of the AV plane compared with controls which was more pronounced at the sites of infarction. The mean value of the AV plane displacement (AV mean) correlated linearly with the left ventricular (LV) ejection fraction calculated by radionuclide angiography (r = 0.87, p less than 0.001, SEE = 6.2). An AV mean of 10 mm or more had a high sensitivity (95%) and specificity (82%) in defining a normal ejection fraction (greater than or equal to 50%). A high correlation coefficient was found between LV wall motion index and the AV plane displacement. Thus, in acute MI the LV function can be assessed noninvasively using AV plane displacement. PMID- 1747970 TI - High-energy catheter ablation of cardiac arrhythmias: an outmoded technique in the 1990s. AB - Catheter ablation has become an accepted technique for creating complete heart block in patients with drug refractory supraventricular tachycardias. However, it remains experimental for other indications, such as ablation of accessory pathway or ventricular tachycardia. The use of high energy defibrillator discharges is associated with adverse effects which greatly contribute to the limitations of the technique. Advances in technology have led to newer methods, such as radiofrequency and low energy capacitive discharge, which hold significant advantages over the conventional high energy technique, to the extent that the use of defibrillator discharges should now be considered outmoded and potentially damaging. Radiofrequency is the technique of choice for accessory pathway ablation and modification of AV conduction, and low energy capacitive discharge is the preferred method for creation of complete heart block. There are currently no acceptably safe and efficacious catheter techniques for treating ventricular tachycardia, and more research needs to be done in this area. The potential for the success of these techniques depends to an extent on the creation of new standards of practice for catheter ablation. There has been no unbiased comparative assessment of the different techniques, and consequently no consensus exists on the preferred technique and technologies which should be used. Only within the framework of these standards can the technique achieve significant clinical utility. PMID- 1747971 TI - Improved diagnosis and characterization of postinfarction left ventricular pseudoaneurysm by cardiac magnetic resonance imaging. AB - A patient with a ruptured left ventricular pseudoaneurysm complicating an acute posteroinferior myocardial infarction is described. Left ventricular pseudoaneurysms are a rare complication of acute myocardial infarction, usually occurring with inferior and/or posterior infarction. In contrast to true aneurysms, pseudoaneurysms are much more likely to rupture, regardless of size, causing hemopericardium and death. Therefore, once the diagnosis has been confirmed, prompt surgical resection is the current accepted treatment. The most accurate noninvasive diagnostic method has been echocardiography, with recent reports suggesting improved diagnosis with color flow Doppler echocardiography. Ventriculography confirms the diagnosis with more accurate anatomic detail, but is an invasive procedure. In our patient, two-dimensional and color Doppler echocardiography could not demonstrate the suspected pseudoaneurysm, which was demonstrated by ventriculography. However, magnetic resonance imaging (MRI) demonstrated the pseudoaneurysm, showing detailed anatomy not obvious on ventriculography. Before surgery could be performed, the patient died and was autopsied. Heart sections corresponding to MRI planes confirmed the MRI findings. A review of the literature has revealed no similar reports using MRI in the diagnosis of postinfarction pseudoaneurysms. Major advantages of MRI are generation of three-dimensional soft tissue images noninvasively, and generation of tissue contrast by rapid imaging sequences, obviating the need for contrast injection. Major disadvantages of MRI are the high cost of instrumentation, nonportability, and a requirement for patient immobility during the study. In cases of suspected pseudoaneurysm with equivocal echocardiography findings, MRI could provide early diagnosis, leading to early surgical intervention and increased patient survival. PMID- 1747972 TI - Thrombolytic therapy in spontaneous coronary artery dissection. AB - A 42-year-old female with no cardiac risk factors had an acute anterolateral myocardial infarction treated with intravenous (IV) tissue plasminogen activator (t-PA). Selective coronary cineangiography a week later revealed extensive dissection of the left anterior descending coronary artery (LAD) and its second diagonal branch. Sixteen months later, she is asymptomatic. This is the fifth reported case of spontaneous coronary artery dissection treated with thrombolytic therapy during the acute event with uneventful recovery. PMID- 1747973 TI - Thrombolytic therapy in acute myocardial infarction following prolonged cardiopulmonary resuscitation. AB - Thrombolytic therapy was administered to a 49-year-old woman with an acute anterior wall myocardial infarction after having prolonged cardiopulmonary resuscitation for 13 minutes. On admission, there was no clinical or radiographic evidence of gross trauma. There was no significant morbidity and the patient recovered to a completely functional status. The literature of thrombolytic therapy after cardiopulmonary resuscitation is reviewed. In the absence of gross trauma from cardiopulmonary resuscitation, thrombolytic therapy in acute myocardial infarction should not necessarily be excluded because of the duration of resuscitation. Further experience with such patients will shed additional light on efficacy and safety. PMID- 1747974 TI - Paul Dudley White: the father of American cardiology. PMID- 1747975 TI - Ingestion of fluoride from dentifrices by children aged 12 to 24 months. AB - The increase of dental fluorosis is largely imputable to the ingestion of dietary fluoride supplements and fluoride toothpastes. However, the toothbrushing habits of very young children is poorly documented. The purpose of this pilot study was to determine the toothbrushing habits of 12- to 24-month-old children and to estimate the quantity of fluoride ingested during toothbrushing. Fifty-nine parents completed a questionnaire regarding the toothcleaning habits of their children. When a dentifrice was used, a dental hygienist scheduled a meeting with the parents in order to observe and measure the amount of toothpaste used. Of the 36 parents who cleaned the teeth of their children, 69% used a toothpaste. Furthermore 20% of the children ingested more than 0.25 mg of fluoride per day by toothbrushing alone. Therefore the practice of toothbrushing and the use of fluoridated dentifrices are widespread among 12- to 24-month old children, and the amount of fluoride ingested from toothpaste could constitute a substantial proportion of the total daily intake of fluoride. Several measures are suggested to enhance the safe use of fluoride dentifrices. PMID- 1747976 TI - Neonatal vein of Galen malformations: experience in developing a multidisciplinary approach using an embolization treatment protocol. AB - A multidisciplinary team approach using a staged transcatheter embolization and neurosurgical protocol was applied to 22 patients with neonatal presentation of vein of Galen malformations over a 12 year period. Aggressive medical therapy was combined with interventions including: ventricular shunting, transcatheter embolization, retrograde transtorcular embolization, and neurosurgical obliteration. There was a high frequency of high output cardiac failure, multiple organ system dysfunction, seizures, hydrocephalus, visual, developmental and neurological disability. Of the first 11 patients, five survived; four with seizures and three with marked retardation. Of the last 11 patients, six survived; five with seizures but only one with retardation. Despite persistently high morbidity and mortality, our continuously evolving protocol offers these otherwise hopeless patients some chance of survival. PMID- 1747977 TI - Normal and pathologic laughter in children. AB - Laughter is a partly involuntary act involving complex pathways in the central nervous system. Laughter normally has positive effects on emotions; however, pathologic laughter is not related to emotion and occurs independent of a stimulus in the environment. This paper outlines normal laughter and the etiology of pathologic laughter, considering both congenital and acquired causes. PMID- 1747978 TI - Polyuria in childhood. AB - Polyuria may result from either a water or a solute diuresis. Although the history and physical examination may provide clues to the cause of the polyuria, the definitive diagnosis requires laboratory tests which focus on the osmolality of the urine and serum in combination with the urine volume and the rate of excretion of osmoles. An isoosmolar or hyperosmolar urine is found in children with a solute diuresis or in normal children, whereas a hypoosmolar urine is found in children with a water diuresis. In the latter case, a low serum osmolality suggests primary polydipsia whereas a high serum osmolality suggests antidiuretic hormone (ADH) deficiency or insensitivity. A water deprivation test is necessary when the initial evaluation fails to establish the cause of polyuria. A vasopressin test enables the differentiation between neurogenic and nephrogenic diabetes insipidus (DI). PMID- 1747979 TI - Parental request for a "drug test": what should the caring pediatrician do? PMID- 1747981 TI - Early meningitis. PMID- 1747980 TI - Congenital complete arterio-ventricular block with aneurysms of the ascending aorta and main pulmonary artery. PMID- 1747983 TI - Smoking cessation. PMID- 1747982 TI - Cigarettes and cigarette smoking. AB - Tobacco use was widespread in the New World by the time of the first voyage of Columbus; however, it is only in the last century that the use of tobacco as cigarettes has been prevalent. The milder tobacco and more acidic smoke of cigarettes lead to the deeper inhalation of tobacco into the lung with resultant deposition and absorption of the addicting, toxic, and carcinogenic components of the smoke. More than 4000 individual constituents have been identified in cigarette smoke, and the relative concentrations of these constituents vary widely between brands of cigarettes. Tar yield, a measure of the total particulate matter of the smoke, varies markedly with the characteristics of the cigarette manufacture and with the pattern of inhalation. As a result, tar is not a good measure of the dose of toxic or carcinogenic agents received by the individual smoker. The particle size of cigarette smoke is in the range that will lead to deposition in the airways and alveoli of the lung, and many of the gas phase constituents are absorbed across the alveolar capillary membrane. The irritant agents in the smoke cause acute and chronic changes in lung structure and function that may result in greater retention of carcinogens within the lung and increased vulnerability of the lung to the effects of these carcinogens. Carcinogens and other constituents of cigarette smoke are also absorbed into the blood and metabolized to active forms through microsomal enzyme systems induced by cigarette smoke. The cellular influx of neutrophils and alveolar macrophages that is part of the inflammatory response may be the precursor of the alveolar wall destruction that results in emphysema. The prevalence of smoking is not uniformly distributed across the population. Men began smoking in large numbers very early in the century, but women began to smoke in large number only at the time of the Second World War. Men born after 1930 have been less likely to take up smoking than their older counterparts. The prevalence of smoking is currently declining in both men and women. PMID- 1747984 TI - Health effects of cigarette smoking. AB - Cigarette smoking is associated with increased overall morbidity and mortality. Smoking is a cause of cancer of the lung, oral cavity, larynx, bladder, and renal pelvis and a contributing factor in the development of cancer of the pancreas, stomach, cervix, liver, penis, and rectum. Smokers are at greater risk for coronary artery disease, cerebrovascular disease, and atherosclerotic peripheral vascular disease. Cigarette smoking is the single most important risk factor for chronic obstructive pulmonary disease and is associated with lower levels of FEV1 and increased respiratory symptoms and infections. Women who smoke during pregnancy have an increased incidence of complications, especially intrauterine growth retardation. Peptic ulcer disease is more common in smokers than in nonsmokers. Finally, involuntary smoke exposure is associated in adults with an increased incidence of lung cancer and possibly greater mortality rates from ischemic heart disease and in children with more frequent lower respiratory tract illnesses and reduced lung growth. PMID- 1747985 TI - Identification of the high-risk smoker. AB - The burden of smoking-related disease can be reduced through smoking prevention and cessation. While physicians should counsel all patients who smoke, disease risks are not uniform among smokers. The smokers of the largest numbers of cigarettes are at greatest risk, as are those who started at younger ages. In addition, other factors determined the likelihood of developing a smoking-related disease. Physicians can use the combination of smoking with these additional risk factors to target smokers for intervention, whether education, cessation, or appropriate screening. PMID- 1747986 TI - Health benefits of smoking cessation. AB - Extensive evidence has now accumulated on the health consequences of smoking cessation. With few exceptions, disease risks are reduced after smoking cessation and continue to drop as abstinence is maintained. The review of the evidence in the 1990 Report of the Surgeon General led to major conclusions that establish smoking cessation as a clear priority for health care providers. PMID- 1747987 TI - Basic and clinical psychopharmacology of nicotine. AB - Nicotine acts on nearly every physiological system of the human body. While the actions of nicotine on the autonomic nervous system may be of interest in understanding possible deleterious long-term effects of smoking on the cardiovascular system, the actions of nicotine on the central nervous system are of the most interest in understanding why people smoke. Many studies of the effects of nicotine on human cognitive function have been performed. Improvement in attention, learning, reaction time, and problem solving have been reported. However, most of the results are inconclusive owing to methodologic problems. Whether the enhanced performance observed after smoking is attributable to relief of symptoms of abstinence or to a primary effect of nicotine on the brain is not clear. The pharmacodynamic effects of nicotine must be considered in the design of studies of the effects of nicotine on human performance. It is not known if the effects of nicotine on performance are subject to tolerance. The facilitation of performance, perceived as a reinforcement, may tend to lessen throughout the day, as do other effects of nicotine. Studies of chronic tolerance to the behavioral effects of nicotine are needed; comparisons between regular smokers and occasional smokers may be helpful. At present, the facilitatory actions of nicotine on human performance have been explained in terms of arousal. However, nicotine actions cannot be explained in terms of this single concept. Different processes, including attention, stimulus evaluation, and response selection, appear to be involved in the effect of nicotine on human information processing. Finally, one must consider that the predominant effects of nicotine may differ among individuals, as different people smoke for different reasons, and the motives for (rewards of) smoking may vary in different situations. PMID- 1747988 TI - Cigarette smoking and addiction. AB - Tobacco use is a form of drug addiction, as shown by studies assessing the abuse liability of tobacco and nicotine in humans and animals. Tobacco experimentation frequently leads to daily use, which is characterized by a highly consistent pattern of drug intake. Such a pattern is controlled by the biologic concentrations of nicotine, a psychoactive constituent of tobacco smoke. Nicotine is a euphoriant, self-administered by humans as well as by animals in laboratory settings. Nicotine controls smokers' behavior in such a way that reducing or suppressing tobacco consumption produces a withdrawal syndrome characterized by irritability, difficulty concentrating, cognitive impairments, and weight gain. Nonpharmacologic factors are also important determinants of tobacco addiction that interfere with successful cessation. Strategies to treat tobacco addiction are comparable to those developed for other drug addictions. For example, therapy may include the use of alternate forms of nicotine and possibly also nicotine antagonists and medications targeted to alleviate specific withdrawal symptoms, if such therapies become available. As in all drug addiction treatment strategies, behavioral intervention is important whether or not a medication is used. PMID- 1747989 TI - Determinants of cigarette smoking. AB - Smoking is a complex process influenced by social, environmental, psychologic, and biologic factors. This article explores the multiple determinants of smoking and how these variables interact to promote the persistence of smoking. Further examination of how smoking persistence varies in relation to several specific diseases is discussed. PMID- 1747990 TI - Process of smoking cessation. Implications for clinicians. AB - The process of smoking cessation involves progression through five stages of change: precontemplation, contemplation, preparation, action, and maintenance. Most patients are not prepared to take action on their smoking, yet most smoking cessation programs are designed for smokers who are so prepared. Small percentages of smokers register for action-oriented cessation programs. How much progress patients make after an intervention is directly related to what stage they are in prior to intervention. The stages of change can be quickly assessed with four questions. Physicians can then be more effective with a broader range of patients by matching their interventions to the patients' stage of change. Helping patients progress just one stage can double their chances of not smoking 6 months later. Providing personalized information about the cons of smoking, asking affect-arousing questions, and encouraging patients to re-evaluate themselves as smokers are interventions physicians can use to help patients who are not prepared to quit smoking. Behavioral interventions, such as providing substitutes like nicotine gum and removing or altering cues for smoking, are most helpful for patients who are ready to take action. The use of a stage-matched, patient-centered counseling intervention can help physicians to feel less frustrated and more effective in their efforts to help a broad range of their patients. PMID- 1747991 TI - Methods for smoking cessation. AB - Smoking cessation treatment consists of three phases: preparation, intervention, and maintenance (support and coping strategies). Although most people who quit smoking do so without going through a formal program, many people act on the advice of a health professional. Self-help techniques appear to be cost effective in terms of their minimal use of professionals. The popularity of hypnosis and acupuncture as quitting methods are not warranted by their quit rates. Quit rates can be improved if physicians provide more help to their patients than just simple advice and warnings. PMID- 1747992 TI - The physician's role in smoking cessation. AB - Physicians have many opportunities to facilitate smoking cessation among individual patients, and this could be complemented by efforts to curb smoking at the community level. If every physician advised all smokers to quit, there would be considerable public health benefit from the additional 5% to 10% of smokers who followed the advice. The benefits would be substantially greater if the interventions were targeted to the smoker's stage of change and with ongoing participation by the physician in the smoking cessation process. Possibly as important as the physician's active role with individual smokers are community wide efforts to curb tobacco smoking. These efforts are essential to the prevention of the initiation of cigarette smoking among children and adolescents. Changing societal norms regarding cigarette smoking will not only decrease the numbers of future smokers but will also assist current smokers in cessation efforts. PMID- 1747993 TI - Pharmacologic approaches to smoking cessation. AB - Only 25 years ago, tobacco dependence was believed to be a simple overuse problem. Research in the last 5 years has demonstrated a much more complex and profound neurochemical and behavioral disorder. Nicotine receptors in the locus coeruleus and the midbrain mesolimbic dopaminergic system activate both arousal state and enhance cognitive functioning (locus coeruleus) and activate the brain's "pleasure center" (mesolimbic system). Pharmacologic treatments, which must be completely integrated into the behavioral treatment plan, alter these profound central nervous system nicotine effects. Currently the only agent with clear scientific evidence for treatment efficacy is nicotine itself. Available only in a transmucosally delivered ion-exchange resin as nicotine polacrilex (Nicorette), nicotine should soon be available in other delivery forms that will have different absorption kinetics: transdermal patch, nasal spray, and vapor inhaler. Other agents in various phases of preclinical and clinical evaluation include 5-HT1A partial agonists such as buspirone; alpha 2-noradrenergic agonists such as clonidine; tricyclics such as doxepin; serotonin re-uptake antagonists such as fluoxetine; ACTH; 5-HT2 antagonists such as ritanserin; central excitatory amino acid inhibitors such as kynurenate; and calcium channel blockers. PMID- 1747994 TI - Maintenance of smoking cessation. AB - Relapse is a frequently encountered problem in smoking cessation. With a cognitive-behavioral model of the relapse process, we can describe high-risk situations where smoking first recurs, the process by which people end up in these situations, and typical responses to violations of abstinence. The model posits that individuals are actively coping with situation-specific urges to smoke that result from prior conditioning. Individuals' beliefs in their ability to cope with urges are critical. Clinical strategies based on the model include assessment of risk profiles, understanding and anticipating high-risk situations, debriefing and reinterpreting lapses in abstinence, and limiting risk through lifestyle changes. These strategies can be incorporated into brief medical office visits. Recommended procedures include systematic but brief assessment, encouragement, goal setting, planning for risk, reinterpreting lapses, recommendations for lifestyle changes, and follow-up appointments. PMID- 1747995 TI - Community-based programs for smoking cessation. AB - Overall, there is a wide range of programs offered at the community level. Most of the group cessation clinics, both nonprofit and commercial, typically offer group support, behavior modification, and stress and weight management, with similar emphases in their companion self-help manuals. It often is difficult to distinguish between the various methods employed by the diverse programs, with those that offer maintenance and relapse prevention components faring the best. In general, the multiple-component programs, whether group or self-help packages, seem to hold the most promise for achieving and maintaining abstinence; however, there is some evidence that overwhelming the smoker with too many new behaviors and skills lowers the effectiveness of otherwise successful components. The challenges for community-based programs will be to modify and adapt their materials and sessions to address the needs uncovered in the recent emphasis on the process of smoking cessation. Specifically, program content must address the issue of recycling and relapse prevention. Smokers who have made unsuccessful quit attempts must be able to reframe those attempts in a positive manner, so that they are motivated to try again. Similarly, recent quitters need the skills and motivation to remain abstinent. Although some cessation programs allow clients to participate in future sessions or meetings for little or no extra cost, few have any strategies for dealing with long-term maintenance. As community-based programs incorporate these elements of cessation, quit rates are likely to increase. An additional challenge is found in the difficulty of reaching the hard-core, heavy smoker. There is little doubt that light-to moderate smokers find it easier to achieve long-term cessation. Cessation programs that motivate heavy smokers to attempt to quit or that include adjunct therapies to assist the heavy smoker (i.e., nicotine gum) to quit smoking are likely to be positively received. Currently, however, efforts specifically designed to assist heavy smokers are experimental. A final challenge is to adapt materials and sessions to motivate and assist the hard-to-reach smokers. Increasingly, smoking is becoming a habit of individuals in lower socioeconomic groups, including minorities, non-high school graduates, and young women. Avenues that have been used to reach white middle-class Americans are not easily transferred to such groups. Some attention is already being paid to development of more culturally appropriate materials (e.g., the ALA Manual oriented to blue collar workers and the ACS focus on pregnant women); however, it remains a challenge to motivate members of these groups to participate in smoking cessation activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1747996 TI - National programs for smoking cessation. AB - The smoking cessation effort has made tremendous progress since the 1964 Report of the Surgeon General described the health hazards of smoking. The impact of these efforts on smoking is particularly impressive when the current smoking level is compared with levels of smoking projected from trends apparent before that 1964 report, levels that might have been reached if there had been no national stop-smoking campaign. Because of the campaign, an estimated 35 million Americans were nonsmokers in 1985 who would otherwise have been smokers. If these figures are projected to the year 2000, the campaign will have postponed more than 2 million deaths. Therefore, reducing the prevalence of smoking in adults from about 40% in 1964 to 29% in 1987 can be considered a tremendous public health achievement. Among those who did take up smoking, there is also reason for some optimism. By 1987, more than 38 million Americans had quit smoking; this figure represents nearly half of all living adults who ever smoked. The 1990 Report of the Surgeon General gave a positive message to the 50 million Americans who continue to smoke by describing the health benefits of quitting for all the major smoking-related diseases. PMID- 1747997 TI - Separation of ovine IgG1 and IgG2 on protein A-sepharose. AB - A method using protein A-Sepharose chromatography was developed to separate and purify ovine IgG1 and IgG2. The IgG1 eluted from protein A-Sepharose at pH 6.8 and IgG2 eluted at pH 4.5. This method was used to show the specific transfer of IgG1 from the colostrum to newborn lambs. After separation on protein A-Sepharose both IgG1 and IgG2 were pure as analyzed by isoelectric focusing, Western Blotting and SDS-PAGE. The isoelectric points for the immunoglobulins were calculated to be 3.5 for IgG2 and a range from 6.2 to 8.1 for IgG1. The subclass, IgG1, was present in the whey and was the subclass that was found in the serum of lambs after being fed colostrum. The ewe sera had a decrease of both IgG1 and IgG2 at the time of lambing compared to 2 weeks prior to parturition. PMID- 1747998 TI - Gonadotropin releasing hormone (GnRH) induced luteinizing hormone (LH) secretion from perifused equine pituitaries. AB - In vitro responsiveness of the horse anterior pituitary (AP) gonadotropes to single and multiple GnRH challenges was examined. The pituitaries were collected from reproductively sound mares in estrus (n = 5) and diestrus (n = 5). Uniform 0.5 mm AP slices were subdivided using a 3 mm biopsy punch and then bisected for use in the perifusion chamber. Four bisected sections per chamber were perifused at 0.5 ml/min at 37 C for 560 min in Medium 199 saturated with 95% 0(2)/5% CO2. Ten minute fractions were collected after an initial 2 hr equilibration period. Four different treatment regimes of GnRH (10(-10) M) were evaluated: (A) three consecutive 10 min GnRH pulses separated by 80 and 100 min, respectively; (B) a single 120 min GnRH infusion; (C) a 10 min GnRH pulse followed 80 min later by a 120 min GnRH infusion and (D) two 10 min GnRH pulses separated by 60 min followed 80 min later by a 120 min GnRH infusion. Estimated total pituitary LH content was higher in estrous than diestrus mares (p less than 0.05). The total amount of LH released in response to GnRH tended to be greater in estrus than diestrus (p less than 0.1), whereas the percentage of LH released in estrus and diestrus was similar. An increase in the area under the LH response curve was noted with each successive 10 min pulse of GnRH during both estrus and diestrus (p less than 0.05), demonstrating a self-priming effect of GnRH. In addition, a significant increase in the peak LH amplitude (p less than 0.05) and the slope to peak amplitude (p less than 0.05) were observed for the 120 min GnRH pulse in regime C and D indicating that prior exposure to short-term pulses of GnRH increased the acute LH secretory response. These results suggest that in the cycling mare (1) the responsiveness of the pituitary (amount of LH released as percent of total LH) is similar in both estrus and diestrus, however, the magnitude of the LH response (total microgram amount of LH released) differs with the stage of the estrous cycle, being highest in estrus, and appears to be related, in part, to pituitary LH content and (2) GnRH self-priming occurs independently of the stage of the estrous cycle. Furthermore, we have demonstrated that the pulsatile mode of GnRH can act directly on the anterior pituitary to dictate the pulsatile release pattern of LH in the cycling mare. PMID- 1747999 TI - Luteotropic influence of the ovine uterus. AB - Preliminary observations indicated that the ovine uterus might play a contributing role in the development of the corpus luteum. In order to better define this putative relationship, we monitored luteal function in mature ewes that were hysterectomized or sham-operated at different intervals following induction of ovulation. Corpora lutea formed following hysterectomy carried out immediately after ovulation were subnormal. Circulatory concentrations of progesterone in these animals began to ascend normally, but then achieved a plateau level less than that of control animals. This was attributed to reduced size of the luteal gland, and not to anomalies per unit tissue in morphology or content of progesterone. Luteal activity was not altered in ewes hysterectomized later in the estrous cycle (Day 5). However, when such a luteal phase was terminated by exogenous luteolysin, corpora lutea formed subsequently were defective. It appears that the ovine uterus produces a hormonal factor during metestrus that augments the growth potential of the corpus luteum. PMID- 1748000 TI - Luteinizing hormone secretion in hypophysial stalk-transected gilts given hydrocortisone acetate and pulsatile gonadotropin-releasing hormone. AB - The site within the hypothalamic-pituitary axis at which cortisol acts to inhibit luteinizing hormone (LH) secretion was investigated in female pigs. Six ovariectomized, hypophysial stalk-transected (HST) gilts were given 1 microgram pulses of gonadotropin releasing-hormone (GnRH) iv every 45 min from day 0 to 12. On days 6-12, each of 3 gilts received either hydrocortisone acetate (HCA; 3.2 mg/kg body weight) or oil vehicle im at 12-hr intervals. Four ovariectomized, pituitary stalk-intact gilts served as controls and received HCA and pulses of 3.5% sodium citrate. Jugular blood was sampled daily and every 15 min for 5 hr on days 5 and 12. Treatment with HCA decreased serum LH concentrations and LH pulse frequency in stalk-intact animals. In contrast, serum LH concentrations, as well as the frequency and amplitude of LH pulses, were unaffected by HCA in HST gilts and were similar to those observed in oil-treated HST gilts. We suggest that chronically elevated concentrations of circulating cortisol inhibit LH secretion in pigs by acting at the level of the hypothalamus. PMID- 1748001 TI - Effect of bovine growth hormone gene expression, sex and age on plasma gonadotropins, estrone and testosterone in prepuberal pigs. AB - Chronic supraphysiological blood levels of growth hormone (GH) may retard sexual maturation in swine. Pigs used in this study included four founder transgenic pigs (two gilts and two boars) expressing a mouse transferrin (TF) promoter fused to a bovine (b) GH structural gene, 13 second- or third- generation transgenic pigs (seven gilts and six boars) expressing a mouse metallothionein (MT) promoter fused to a bGH structural gene and 16 control littermates (eight gilts and eight boars). Blood plasma levels of LH, FSH, estrone and testosterone were measured to determine whether expression of bGH genes altered secretion of hormones between 80 and 180 days of age. Presence of a bGH gene was detected by hybridization of DNA in dot blots of tail biopsies. Expression of a bGH gene was detected by radioimmunoassay of plasma bGH. In four TFbGH founder transgenic pigs bGH ranged from 164 to 1948 ng/ml; in one MTbGH transgenic boar of line 3104 bGH was 1211 ng/ml; and in 12 pigs of line 3706 bGH ranged from 25 to 190 ng/ml. Expression of bGH in transgenic pigs lowered (P = .0192) plasma LH with no significant differences between sexes, had no significant effect on plasma FSH and lowered plasma estrone (P = .0001) and testosterone (P = .0269) in boars (but not gilts). Plasma estrone and testosterone were higher (P = .0001) in boars than in gilts. Plasma FSH was higher (P = .0001) in gilts than boars and decreased (P = .0001) with advancing age in gilts but not in boars.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748002 TI - Effect of dietary intake on concentrations of insulin-like growth factor-I in plasma and follicular fluid, and ovarian function in heifers. AB - The objective of this study was to determine if alterations in dietary intake of heifers can influence IGF-I concentrations in plasma and(or) follicular fluid (FFL), size of follicles, and steroid concentrations in FFL (as an indicator of steroidogenic capacity). Cyclic heifers [n = 23; mean +/- SE body weight (BW) = 373 +/- 7 kg] were individually fed for 10 weeks either: a) 1.8% of BW in dry matter (DM) per d (GAIN; n = 7), b) 1.1% of BW in DM per d (MAINT; n = 8) or c) 0.7% of BW in DM per d (LOSE; n = 8). After 10 wk of treatment, heifers were ovariectomized 36-40 hr after the second injection of prostaglandin F2 alpha analog (2 injections 11 d apart), and plasma and ovaries were collected. Heifers weighed 444 +/- 13,387 +/- 8 and 349 +/- 9 kg in the GAIN, MAINT and LOSE groups, respectively, at time of ovariectomy. Mean diameter of follicles greater than or equal to 10 mm was greater (P less than .05) for GAIN (15.6 mm) than for MAINT (11.0 mm) or LOSE (12.5 mm) heifers. Numbers of follicles and concentrations of IGF-I in plasma and FFL did not differ (P greater than .20) between LOSE, MAINT and GAIN heifers. Progesterone concentrations were greater (P less than .05) in small and medium follicles of GAIN than MAINT or LOSE heifers, but were unaffected by diet in large follicles. Estradiol concentrations in FFL in small, medium and large follicles were unaffected (P greater than .20) by dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748003 TI - Bovine corpus luteum function after removal of granulosa cells from the preovulatory follicle. AB - Experiments were conducted to determine the effects of removing granulosa cells from bovine preovulatory follicles on subsequent corpus luteum (CL) function. Holstein heifers were assigned to three groups: untreated controls (n = 6), removal of granulosa cells (n = 9) and removal and return of granulosa cells (n = 7). Surgery was performed 18-24 hr after the onset of estrus and in all cases after the preovulatory luteinizing hormone (LH) surge. Jugular venous blood was collected and estrous activity monitored twice daily. Corpora lutea were formed in six heifers in each group. Concentrations of plasma progesterone were reduced (P less than 0.05) on Days 7-17 in heifers from which granulosa cells were removed when compared to the other two groups. There were no differences in the lengths of the estrous cycles nor concentrations of LH in the three groups. In summary, these experiments support the concept that granulosa cells make a substantial contribution to the output of progesterone by the cyclic CL but may have a limited role in determining the functional lifespan of the CL. These experiments also establish the fact that granulosa cells develop into functional luteal cells after their removal and return to the preovulatory follicle. PMID- 1748004 TI - Changes in the concentration of mRNAs for the inhibin subunits in ovarian follicles after administration of gonadotropins to progestin treated ewes. AB - RNA was extracted from single or small groups of ovine ovarian follicles after treatment of ewes with FSH and/or LH. The content of mRNA for the alpha-inhibin and beta A-inhibin subunits was analyzed by hybridization with specific cDNA probes. All ewes were treated with progestin vaginal pessaries to suppress spontaneous preovulatory follicle maturation and ewes were given three intramuscular injections of gonadotropins at 8-hr intervals starting 24 hr prior to collection of ovaries. In experiment I, both Schering-FSH and NIDDK-oFSH-17 (oFSH) significantly increased alpha- and beta A-inhibin mRNA per ewe in 2-5 mm follicles and tended to increase alpha- and beta A-inhibin mRNA in large (greater than 5 mm) follicles. In experiment II, oFSH and NIDDK-oLH-25 (oLH) were administered in a 2X2 factorial arrangement. Separate administration of oFSH or oLH increased (P less than .05) the alpha-inhibin mRNA concentration in large follicles. alpha-inhibin mRNA concentration in 4-5 mm follicles was also increased by oFSH but was decreased by oLH. Concomitant treatment with oFSH and oLH did not change alpha-inhibin mRNA concentrations from those measured in oFSH treated ewes. In experiment II, beta A mRNA concentrations followed a pattern similar to that of alpha A mRNA, but the differences were not statistically significant. We conclude that, in the ewe, exogenous FSH increases the concentration of inhibin mRNA in the whole follicle. The ability of exogenous oLH to alter expression of the inhibin subunit genes may depend upon the stage of follicle maturation. PMID- 1748005 TI - In situ hybridization analysis of ovarian prostaglandin endoperoxide synthase mRNA throughout the periovulatory period of the ewe. AB - Cellular alterations in level of expression of mRNA encoding for prostaglandin endoperoxide synthase were quantified within ovarian tissues of sheep obtained before, during and after induction of the preovulatory surge of LH and ovulation with LHRH. This was accomplished by isotopic in situ hybridization using a selective cRNA probe to ovine prostaglandin endoperoxide synthase mRNA. A significant elevation in mRNA was detected within the theca interna of the preovulatory follicle at 8, 16 and 24 hr following administration of LHRH. Very close to the time of ovulation (ie., at 24 hr post-LHRH) a marked rise in mRNA was observed in association with epithelial cells covering the apical surface of the follicle. Ovarian cyclooxygenase metabolites of arachidonic acid produced during the ovulatory process in the ewe originate within the thecal layer and germinal epithelium of the follicle destined to ovulate. PMID- 1748006 TI - The emergence of methicillin resistant Staphylococcus aureus in extended care facilities in northern Connecticut between 1986 and 1990. AB - Methicillin resistant Staphylococcus aureus (MRSA) is recognized as a pathogen of significant morbidity in hospital facilities. The microorganism can also be recovered from clinical specimens taken from patients who are residents of extended care facilities (ECFs). This report is a five-year retrospective review of the emergence and spread of MRSA isolates within ECFs located in north central Connecticut and their susceptibility profile over that time span. PMID- 1748007 TI - Leuprolide with flutamide for complete androgen ablation: therapeutic alternative for advanced prostatic cancer (stage D2). PMID- 1748008 TI - The leading edge? PMID- 1748009 TI - Taking fiduciary relationships seriously. PMID- 1748010 TI - Conservative treatment for myocardial infarction. PMID- 1748011 TI - Proteoglycans nondissociatively extracted from different zones of canine normal articular cartilage: variations in the sedimentation profile of aggregates with degree of physiological stress. AB - Proteoglycans were extracted and purified without dissociation (a-A1 preparations) from superficial and deeper layers of high weight-bearing (HWA) and low weight-bearing (LWA) areas of dog normal articular cartilage. These proteoglycans were then characterized by velocity gradient centrifugation. In each of the 4 different topographical regions, the weight average sedimentation coefficients related strongly with total hexuronate content of the tissue. In the superficial layers, almost all aggregates had low sedimentation coefficients: the aggregates were smaller and less abundant in LWA than in HWA. The deeper layers contained an additional population of faster sedimenting aggregates which appeared smaller and less abundant in LWA than in HWA. Quantification and functional characterization of aggregates as well as in vitro aggregating studies showed that the topographical differences in size and content of aggregates were related to differences in content of hyaluronate and link protein in the a-A1 preparations. Superficial a-A1 specimens contained twice as much hyaluronate as deeper a-A1 preparations and their hyaluronate content increased with degree of physiological stress. Deeper a-A1 specimens from weight-bearing areas did not differ in their hyaluronate content but experiments assessing the saturation with link protein of these different a-A1 preparations suggested that specimens from HWA contained more active link than those from LWA. In contrast, the capacity of aggregation of a-A1D1D1 proteoglycan monomers as well as the molecular weight (Mr = 5 x 10(5) and aggregating capacity of hyluronate molecules appeared very similar in all a-A1 preparations from areas of articular cartilage. It is hypothesized that the synthesis of the three constituents necessary for aggregate formation (i.e. proteoglycan monomers as well as hyaluronate and link protein molecules) increases with degree of physiological load and that aggregation helps to maintain within cartilage the high concentration of proteoglycans that are essential for its biomechanical functions. The reported topographical variations in the distribution of proteoglycan aggregates reflect probably a maximal adaptation of the physiologic and biomechanical properties of the matrix to meet the high stress levels experienced by the articular cartilage in vivo. PMID- 1748012 TI - The right ventricle: anatomy, physiology, and clinical importance. PMID- 1748013 TI - Social skills and antisocial conduct of delinquents. AB - A revised and abbreviated version of the Adolescent Problems Inventory (API) was used to examine the relationship between social skills deficits and antisocial behavior. A factor analysis of the revised API yielded three factors (Immediate Response Demand, Deferred Response Demand, and Antisocial Peer Influence) which were differentially related to specific measures of antisocial responding. Results are discussed in the context of a multifactorial model of juvenile delinquency. PMID- 1748014 TI - Social competence in young children's peer relations: patterns of development and change. AB - Patterns of developmental change and individual differences in social competence were examined in children of depressed and psychiatrically well mothers, during the toddler-to-late-preschool period. Forty-one children were observed in peer interaction at ages two and five under semi-naturalistic laboratory conditions intended to elicit a range of emotions and social skills. Social competence increased with age, but patterns of developmental change were moderated by maternal diagnosis. Low levels of individual stability were identified in children's social competence. PMID- 1748015 TI - The classification of conduct disorders. AB - Empirical data comparing DSM-III and DSM-III-R criteria on conduct disorders were obtained from 100 adolescent juvenile justice center residents. The importance of an ongoing classification of childhood and adolescent psychiatric disorders, with primary emphasis on the diagnosis of conduct disorders, was stressed. Demographic and associated features were presented. DSM-III-R seemed superior to its predecessor in some respects and the severity index in particular may be useful. Direction for further classification modification was suggested. PMID- 1748016 TI - Communication issues in Attention-deficit Hyperactivity Disorder. AB - Children with Attention-deficit Hyperactivity Disorder (ADHD) evidence a variety of pragmatic deficits and are particularly at risk for other speech and language disorders. Speech and language pathologists in educational settings have the special expertise needed for interpretation and treatment of communication issues associated with ADHD. They should contribute more directly to the multi-modality treatment team in creating management programs for these children. PMID- 1748017 TI - Separation reaction of psychiatrically hospitalized children: a pilot study. AB - This paper reports on the development of the Children's Separation Rating Scale (CSRS), its initial reliability and validity, and clinical/research utility with psychiatrically hospitalized children. The CSRS appears to be a reliable and valid instrument, and useful in distinguishing children's separation reaction from their general psychopathology. Findings from this pilot study support the notion that inpatient treatment programs should address the developmental needs and abilities of the various age groups and the particular deficits reflected in their psychopathology. PMID- 1748018 TI - [Case classification as a prerequisite for quality assurance measures- experiences with the PMC system in surgical patients]. PMID- 1748019 TI - [Extension of employment contracts on completion of continuing education]. PMID- 1748020 TI - [Beginning of expiration of medical fee requests only with date of medical fee bill?]. PMID- 1748021 TI - [Operation of inguinal hernia. Classification, choice of procedure, techniques and results]. PMID- 1748022 TI - [Surgical therapy of incisional hernias]. PMID- 1748023 TI - [Zenker's diverticulum. Long-term results after surgical therapy]. AB - Twenty-one patients were treated for Zenker's diverticulum in the Wurzburg University Department of Surgery between 1977 and 1989. Surgery was done in 15 cases (8 single-session resections with myotomy of the upper esophageal sphincter, and 7 resections without myotomy). The postoperative course was uneventful in 73%. Wound infection developed in 2 cases, and suture insufficiency and transient paralysis of the recurrent nerve in one each. In 3 patients, postoperative x-ray prior to release from the hospital revealed retention of contrast medium in a discrete, pocket-like protrusion between the cricoid and the pharynx. Follow-up was done after a mean interval of 4 years (range: 5 months 10.5 years) in 10 of the 15 operated patients. Two of them developed relapses about 1-1.3 cm in size within 8 months and 7 years, resp. Myotomy had not been done in either case. Neither patient had complaints. Esophageal manometry was performed in 6 patients. Resting tone of the upper esophageal sphincter was clearly diminished at 12-30 mm Hg (normal 40-50 mm Hg); maximum contraction pressure was also reduced at 30-75 mm Hg (normal 90-110 mm Hg). However, the decisive factor was the exact temporal coordination of pharyngeal contraction with sphincter relaxation. For this reason it is our unconditional recommendation that myotomy of the upper esophageal sphincter be regarded as an essential step in resection of Zenker's diverticula. PMID- 1748024 TI - [Results of surgical therapy of cervical diverticulum]. AB - Eighteen patients with a pharyngoesophageal diverticulum were operated on at the University Department of Surgery, Mainz, between September 1985 and July 1990. Results are based on follow-up studies of 15 patients. Three patients were operated upon less than six months ago. All patients underwent excision of the diverticulum and a cricopharyngeal myotomy. The mean age was 69 (49-84) years and the average follow-up interval was 30 (6-52) months. Twelve of the fifteen patients are free of symptoms concerning the esophagus since the operation. Two patients who died 17 resp. 22 months after the operation were also free of symptoms concerning the esophagus. In all 11 patients who had a barium contrast, swallowing was normal and no recurrence was found. The results show excision of the diverticulum combined with a cricopharyngeal myotomy to be an effective method with low risk for the long-term removal of pharyngoesophageal diverticulum. PMID- 1748025 TI - [Surgical indications in cricopharyngeal dysfunction]. AB - In 1989, five patients were treated for a cricopharyngeal dysfunction by cervical myotomy. In the past, due to extremely limited indications for surgery, repeated efforts of conservative treatment had been attempted in patients with idiopathic cricopharyngeal dysfunction and tracheopulmonary aspiration and/or permanent inability of oral nourishment. These patients underwent surgery after an interdisciplinary clinical assessment. Four out of five patients showed immediate improvement of their serious symptoms. Cervical myotomy is not expected to be successful in patients with insufficient oropharyngeal propulsion, as we could see in one female patient with severe upper oesophageal sphincter spasm. According to the literature and to our results, approximately 70 to 90% of the patients with idiopathic dysfunction of the cricopharyngeal muscle, who underwent surgery, showed significant improvement or even recovery. Due to the multifactoral genesis of the cricopharyngeal dysfunction it is understandable, that the surgical result is heavily dependent on the preoperative interdisciplinary diagnosis. In summary, for idiopathic cricopharyngeal dysfunction with complications we recommend the early and technically simple operation. PMID- 1748026 TI - [Surgical therapy of ulcer disease. Early and late results of elective and emergency interventions]. AB - Between 6/1974 and 12/1988 910 patients with peptic ulcer disease have been treated operatively. In 523 cases a resection, gastroenterostomy resp. ligation of a bleeding ulcer, in 160 cases with duodenal ulcers a vagotomy, and in 227 cases with perforated ulcers simple closure or primary resection have been performed. During this study the percentage of female patients rose from 32.0 to 39.7. There was also an increase of the mean age of the patients. Operative mortality rate was 7.3% for resection, GE resp. ligation of a bleeding vessel, 0.6% for vagotomies, and 16.3% for perforated ulcers. The fate of all patients was followed regularly. In patients operated before 1985--with a follow-up of 5 16 years--reoperations were necessary in 6.0% following resection, gastroenterostomy resp. ligation, in 7.7% following vagotomy, and in 21.3% following simple closure or primary resection of a perforated ulcer. PMID- 1748027 TI - [Management of pancreatic rupture]. PMID- 1748028 TI - [Stomach rupture caused by barotrauma]. PMID- 1748029 TI - [Perforated ileal diverticulitis--a rare cause of peritonitis]. PMID- 1748030 TI - Trap perches to assess the activity of pyrethrins against the poultry red mite Dermanyssus gallinae in cage birds. AB - Trap perches were utilised to quantify mite recoveries during efficacy tests of pyrethrin formulations against experimental infestations of Dermanyssus gallinae (De Geer, 1778) in budgerigars and pigeons, and to monitor mite recoveries from untreated canaries. Pyrethrins applied topically before infestation significantly reduced the mean numbers of poultry red mites found in both budgerigar and pigeon trap perches, over those in untreated controls (P = less than 0.01). In untreated control budgerigars and pigeons, and in untreated canaries, the percentage recoveries after 48 h were 12.6 +/- 1.6, 4.1 +/- 1.9, and 32.6 +/- 1.6%, respectively (geometric mean +/- SD), and the blood engorgements rates were 71.5 +/- 1.7, 11.9 +/- 5.1, and 90.1 +/- 1.0% respectively. The recovery in trap perches of mites from canaries declined exponentially; 85% of the cumulative total recovered was collected 24 h after infestation, but small numbers were recovered daily up to 96 h (limit of observation). The use of the trap perches is discussed as a way of assessing the efficacy of acaricides, and as a laboratory tool in studies on mite aggregation behaviour or immune responses to mite infestation. PMID- 1748031 TI - Influence of identification ear tags on the numbers of adult Rhipicephalus appendiculatus (Acari: Ixodidae) on the ears of cattle. AB - The influence of ear tags on the number of adult Rhipicephalus appendiculatus was investigated. Tagged ears carried significantly more ticks than untagged ears, but differences decreased with time. Ticks were seen crowding under and close to the back of the tag, on the outside of the ear. PMID- 1748032 TI - Studies on the economics of ticks in Zambia. AB - Two herds of experimental Sanga cattle were maintained under traditional savanna grazing management for three years in the Central Province of Zambia. One herd was kept free of ticks by regular acaricide treatment, while the other was given no tick control. Milk production, growth rate, fertility and mortality were monitored throughout the trial. The tick-free herd performed significantly better than the tick-infested herd, but the value of the additional production was much less than the cost of the acaricide used. It is concluded that there is no economic justification for intensive tick control under these conditions. However, strategic tick control would be justified if the quantity of acaricide used could be reduced by 50% without any major reduction in benefits. The results indicate that treating calves below 45 days of age reduces their performance, as does treating cows during periods of very low tick challenge. Therefore, it seems likely that economically beneficial strategic tick control policies could be developed. PMID- 1748033 TI - Clinical implications of drug interactions with the cytochrome P-450 enzyme system associated with omeprazole. AB - Interactions with the hepatic cytochrome P-450 microsomal enzyme system, as evidenced by statistically significant changes in pharmacokinetic parameters, have been described with some H2-receptor antagonists. Omeprazole is the first of a new class of antisecretory agents inhibiting gastric secretion by blocking hydrogen potassium ATPase. Omeprazole contains a benzimidazole moiety and thus has the potential to interact with the cytochrome P-450 enzyme group. In vitro, in vivo and human clinical studies have assessed whether such an interaction occurs, and the potential clinical consequences, in patients receiving omeprazole therapy. In vitro studies have demonstrated that omeprazole influences O deethylation and N-demethylation in liver microsomes and the clearance and elimination half-life of antipyrine in isolated perfused liver preparations. Overall, the studies reviewed suggest that omeprazole has a differential affinity toward specific cytochrome P-450 isozymes. In vivo animal studies have demonstrated that omeprazole prolongs pentobarbital sleep times and half-life and decreases [14C]-aminopyrine elimination. Human clinical studies have not demonstrated the "all or none" effect of omeprazole on cytochrome P-450-mediated drug interactions, as is seen with cimetidine. These studies confirm in vitro findings that omeprazole is a differential inhibitor of drug metabolism: interactions have been demonstrated with the model drugs aminopyrine and antipyrine, and the therapeutic drugs diazepam, phenytoin, and warfarin but not with theophylline or propranolol. Although caution should be exercised when initiating omeprazole therapy in patients taking concomitant diazepam, warfarin, and phenytoin, clinically significant drug interactions appear unlikely. PMID- 1748034 TI - Applied potential tomography. Noninvasive method for measuring gastric emptying of a solid test meal. AB - Applied potential tomography (APT) is a new noninvasive, nonradioactive method of measuring gastric emptying, which generates profiles of emptying of liquids that are similar to those obtained simultaneously by scintigraphy and dye dilution. This study validates the ability of APT to measure emptying of a solid beefburger test meal from the stomach by comparing the results obtained with those obtained simultaneously by scintigraphy. When acid secretion was inhibited, there was a significant correlation between the two methods for the time taken for half the meal to empty from the stomach and the amount of meal emptied at different time intervals. Furthermore, the profiles of gastric emptying obtained by APT resembled those obtained by scintigraphy in most studies. If acid secretion was not inhibited, there was no correlation between values obtained by the two methods. PMID- 1748035 TI - Tolerance and rebound to H2-receptor antagonists: intragastric acidity in patients with duodenal ulcer. AB - Tolerance to the antisecretory effects of H2-receptor antagonists develops consistently in healthy volunteers. The aim of this study was to determine whether tolerance occurs with repeated dosing of H2-receptor antagonists in patients with duodenal ulcer. Continuous intragastric 24-hr pH measurements were performed in 12 patients with duodenal ulcer in symptomatic remission before, on days 1 and 29, and two days after receiving ranitidine 300 mg four times a day for 34 days. The 24-hr median intragastric pH (interquartile range) was 5.4 (4.4 6.1) on day 1 and 4.6 (4.0-5.2) on day 29 of dosing with ranitidine (not significant). Median nighttime pH was 6.8 (6.3-7.0) on day 1 and 6.8 (6.6-7.1) on day 29 (not significant). During the daytime, the median pH decreased marginally from 4.7 (3.8-5.2) on day 1 to 3.8 (3.0-4.6) on day 29 (P less than 0.03). There was no difference in median intragastric pH during 24-hr, day and night periods before and two days after ranitidine dosing. No significant tolerance or rebound to H2-receptor antagonists was observed in patients with duodenal ulcer disease. This contrasts with data gathered in healthy volunteers and may be due to defects in the regulation of acid secretion in duodenal ulcer disease. PMID- 1748036 TI - Cisapride in treatment of Roux-en-Y syndrome. AB - After Roux-en-Y gastrojejunostomy patients frequently complain of upper abdominal pain, fullness, nausea, and vomiting. This Roux-en-Y syndrome is caused by slow gastric emptying, Roux-limb stasis, or both. Treatment of this syndrome is cumbersome. We evaluated the effect of cisapride on complaints and on transit through gastric remnant and Roux limb in 24 such patients. Thirteen of them had slow gastric emptying and 13 had stasis in the Roux limb (two patients had both). Symptoms and transit were evaluated before and after three weeks of treatment using a questionnaire and scintigraphy. Responding subjects continued therapy and were interviewed again after six months. Seven patients with slow gastric emptying and three patients with Roux-limb stasis had enduring symptomatic relief; all exhibited accelerated transit during therapy: mean half gastric emptying time in the seven patients with slow gastric emptying was 204 +/- 89 min before and 111 +/- 59 min during cisapride (P less than 0.05); mean percentage of radioactivity, emptied from the gastric remnant, which remained in the Roux limb at 60 min in the three patients with Roux limb stasis was 74 +/- 4% before and 25 +/- 10% during cisapride (P less than 0.05). In patients without symptomatic response, transit did not improve. CONCLUSION: with cisapride long-lasting symptomatic relief and improved transit is achieved in about 40% of patients with the Roux-en-Y syndrome. PMID- 1748037 TI - Effect of partial gastrectomy on serum anti-Helicobacter pylori immunoglobulins in peptic ulcer patients. AB - Since biliary enterogastric reflux is suggested to eradicate gastric infection with Helicobacter pylori (HP), we have investigated in a prospective randomized study the effect of partial gastrectomy with either Billroth II or Roux-en-Y anastomosis on infection with HP as assessed by the titers of IgG and IgA antibodies against HP in serum. These antibodies were measured by ELISA in serum of 22 patients before and at 10 days and 6, 15, and 24 months after either Billroth II (N = 11) or Roux-en-Y (N = 11) gastrectomy for peptic ulcer. All patients had HP demonstrated in their preoperative endoscopic gastric biopsies. The preoperative serum IgA antibodies against HP (anti-HP IgA) were increased in 20 of the 22 patients (range 0.21-1.69) while the IgG antibodies (anti-HP IgG) were increased in all 22 patients (range 0.38-1.31). Four of the Billroth II patients had clearance of HP from gastric biopsies accompanied by rapid and pronounced decrease of anti-HP IgA. In contrast, the patients with Roux-en-Y gastrectomy and the Billroth II patients with persistent HP infection had no change in anti-HP IgA after surgery. Anti-HP IgG showed variable results in the four patients without gastric HP infection and was not affected by gastrectomy in the patients with persistent HP infection. We concluded that serum anti-HP IgA, but not anti-HP IgG, is helpful in identifying those patients in whom HP is no longer demonstrable after Billroth II gastrectomy. Gastrectomy with Roux-en-Y anastomosis had no effect on gastric HP infection. PMID- 1748038 TI - Dieulafoy's lesion. Diagnosis and management. AB - A review of 177 cases of upper gastrointestinal hemorrhage due to Dieulafoy's lesion is reported. Dieulafoy's lesion is frequently responsible for severe and recurrent upper gastrointestinal hemorrhage. The lesion was predominantly found in the proximal stomach. Repeat endoscopies were needed in 33% of the patients in order to make the correct diagnosis. When preoperative diagnosis and localization were made, surgery was an effective therapeutic modality. Therapeutic endoscopy was successful in achieving permanent hemostasis in 85% of the reported cases. Re treatment was needed in an additional 10% and surgical therapy in 5% of the cases. Therapeutic endoscopy should be considered initially in all patients. Surgical intervention and angiography with embolization may be effective options if endoscopic therapy is unsuccessful. PMID- 1748039 TI - Roles of in vitro- and in vivo-administered histamine and serotonin in compound 48/80-induced gastric acid secretion in isolated, perfused rat stomach. AB - In this investigation, an isolated, perfused rat stomach system was used to elucidate the roles of histamine, serotonin, and the action of cimetidine, methysergide, and propranolol in relation to the in vivo and in vitro administration of compound 48/80. While histamine administered both in vivo and in vitro stimulated acid secretion in the perfused rat stomach, serotonin, added in vitro, inhibited histamine-induced gastric acid secretion. Cimetidine, given either in vivo or in vitro, blocked histamine-induced acid secretion, and methysergide, but not propranolol, reversed the serotonin-induced inhibition of histamine-stimulated acid secretion. Compound 48/80, given in vitro, caused gastric acid secretion that was blocked by pretreatment with cimetidine. Administered in vivo, however, compound 48/80 inhibited both basal and histamine stimulated acid secretion. This inhibition was partially reversed by pretreatment with methysergide. The absence of inhibition of acid secretion by in vitro administered compound 48/80 may be related to the timing of the serotonin effect. When serotonin was given prior to histamine, it blocked acid secretion, whereas no inhibition occurred when serotonin was administered together with histamine. None of the other agents investigated affected basal acid secretion. PMID- 1748040 TI - Effects of stimulation and inhibition of acid secretion on gastric damage induced by platelet-activating factor. AB - Intravenous administration of platelet-activating factor (PAF) induces extensive damage in rat gastric mucosa. The aim of the present study was to examine whether the presence or absence of acid in the gastric lumen could modify the PAF-induced gastric damage. The effects of inhibition of basal and pentagastrin-stimulated acid secretion by ranitidine on the deep histological gastric damage induced by 30 min of infusion of PAF (100 ng/kg/min) were assessed by using a histological score. Inhibition of basal gastric acid secretion did not prevent the histological gastric damage induced by PAF. Stimulation of gastric acid secretion by pentagastrin significantly increased PAF-induced gastric damage, and this effect was reversed by a dose of ranitidine that returns acid secretion to baseline levels. This acid-related damage was confined to the deep mucosa, since scanning electron microscope analysis ruled out an additional surface damage in PAF-infused rats when gastric acid was stimulated. The data indicate that a certain amount of acid may worsen the deep gastric mucosal damage induced by PAF. PMID- 1748041 TI - CP-66,948: an antisecretory histamine H2-receptor antagonist with mucosal protective properties. AB - CP-66,948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. The affinity of CP-66,948 for the guinea pig atria histamine H2-receptor is 15 times greater than that of cimetidine and seven times greater than that of ranitidine. In vivo, the ED50 value for inhibition of gastric acid secretion in pylorus-ligated rats is 2 mg/kg intraduodenally, and in histamine or pentagastrin-stimulated Heidenhain pouch dogs the antisecretory ED50 values are 0.3 mg/kg per os and 1.0 mg/kg per os, respectively. CP-66,948 also inhibits ethanol-induced gastric hemorrhagic lesions in rats following either oral or systemic administration (ED50 values of 12 mg/kg per os and 6 mg/kg subcutaneously). In addition, the mucosal protective activity is independent of prostaglandin synthesis. CP-66,948 inhibits gastric acid secretion in man, and its mucosal protective activity may provide additional benefits in peptic ulcer therapy. PMID- 1748042 TI - Alterations of intestinal microflora by antibiotics. Effects on fecal excretion, transit time, and colonic motility in rats. AB - The effects of intragastric antibiotics in rats were examined on fecal microflora and excretion and through transit time and cecocolonic myoelectric activity. A solution of nonabsorbable antibiotics infused into the stomach for 20 days had a dramatic effect on the quantity, composition, and bacterial content of rat feces. Both the dry weight and the water content of feces were increased. The amount of short-chain fatty acids in the feces was dramatically lowered. However, neither total nor cecocolonic transit time of solids was affected. The cyclic organization of cecocolonic myoelectric activity was altered by antibiotic treatment, and the motility index, ie, the quantity of myoelectric activity recorded on the colon, progressively increased. An infusion of short-chain fatty acids modified this motor pattern but did not restore activity to a level comparable to that of control animals. In conclusion, intragastric antibiotics dramatically reduced intestinal microflora and increased fecal excretion of dry matter and water but did not affect the transit time of solid gut contents, although they did influence cecocolonic motility. PMID- 1748043 TI - Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation. AB - The fate of 5-aminosalicylic acid (5-ASA), which is used in the treatment of chronic inflammatory bowel diseases, was studied in six healthy volunteers receiving doses of 100 mg and 250 mg intravenous bolus as well as 250 mg per os (slow release). Following intravenous administration, the drug was rapidly eliminated with a plasma half-life of about 40 min, mainly due to rapid metabolism. No parent drug was recovered in feces, and the total recovery following oral administration (30%) was significantly lower than following the intravenous doses (77% and 72%). Nonlinear pharmacokinetics were suggested as the 2.5-fold increase in intravenous dose was followed by a significant relative increase (greater than 2.5) in the renal elimination of 5-ASA, as well as a significant decrease (less than 2.5) in the elimination of the metabolite N acetyl-5-ASA. There was also a trend towards a decreasing total body clearance and metabolic ratio. The present study confirms earlier findings on the pharmacokinetics of 5-ASA and suggests a possible saturation of the N-acetylating system in the dose range studied. This may be of interest in the design of controlled-release formulations and dosage regimes for the treatment of diseases of the small-bowel, where 5-ASA is easily absorbed. Further, for the first time, a marked difference in the intestinal fate compared to the systemic fate of the drug is demonstrated, suggesting alternative presystemic metabolism of 5-ASA, which may bear relevance to its mode of action. Further studies on the pharmacokinetics of 5-ASA, preferably in patients, are warranted. PMID- 1748044 TI - Antibodies to Mycobacterium paratuberculosis in patients with Crohn's disease. AB - IgG antibodies against Mycobacterium paratuberculosis protoplasmic antigen were looked for by an enzyme immunosorbent assay in patients with Crohn's disease, Ulcerative colitis, active pulmonary tuberculosis, past pulmonary tuberculosis, and in healthy controls. Serum reactivity for these antibodies was not correlated to PPD skin test positivity without history of mycobacterial disease. A cutoff based on the mean absorbance value of a pool of healthy blood donors was chosen. Positive values were found in 12/24 (50%) patients with active pulmonary tuberculosis and 2/10 (20%) skin-test-positive subjects with past pulmonary tuberculosis as expected, because antigenic sharing is common among different mycobacteria. The control group of blood donors showed borderline positivities in 3/149 cases (2.01%). Positive values were found in 4/108 (3.70%) patients with Crohn's disease and 2/40 (5%) with ulcerative colitis. We conclude that our data do not support a causal relationship between the M. paratuberculosis and Crohn's disease, but occasional patients with inflammatory bowel diseases show unexpected positivities for these mycobacterial antibodies. PMID- 1748045 TI - Health status and health care use in persons with inflammatory bowel disease. A national sample. AB - We randomly surveyed 997 members of the Crohn's and Colitis Foundation of America with inflammatory bowel disease (320 ulcerative colitis and 671 Crohn's disease) in order to: (1) assess their health status, (2) compare members with ulcerative colitis and Crohn's disease, and (3) determine the correlates of health care use. Data collection included variables relating to physical and psychological symptoms, medication use, daily functional status, perceptions of health, and coping styles. The findings indicate that: (1) despite a number of symptoms and complications related to inflammatory bowel disease, the health status of this population is generally good and may be a result of effective coping styles; (2) those with Crohn's disease have more psychosocial difficulties, which appear related to greater symptom severity; (3) both psychosocial and physical health variables are related to number of physician visits, while primarily physical health variables are related to number of hospitalizations and surgeries. Further studies are needed to determine the representativeness of this self-selected sample with others having IBD. In this study, we have provided the basis for developing a more sensitive measure of health status than currently exists, and one which may have implications for future clinical studies. PMID- 1748046 TI - Breath hydrogen test using water-diluted lactulose in patients with gastrointestinal amyloidosis. AB - To investigate small bowel motility in gastrointestinal amyloidosis, lactulose breath hydrogen tests were performed on 16 patients with histologically proven amyloidosis and 12 age- and sex-matched controls. Fasting breath hydrogen concentration (FBHC) was not significantly different between the two groups, but there was a tendency for FBHC in symptomatic amyloidosis patients (median 31.5, range 3-78 ppm) to be higher than in asymptomatic amyloidosis patients (4, 0-34 ppm, 0.05 less than P less than 0.1) and controls (6, 1-19 ppm, 0.05 less than P less than 0.1). Orocecal transit time (OCTT) was significantly delayed in the amyloidosis group (median 150, range 40-220 min) when compared to the controls (60, 20-110 min, P less than 0.01), but OCTT was not statistically different between symptomatic and asymptomatic amyloidosis patients. These data suggest an impaired motility of the stomach and small intestine in gastrointestinal amyloidosis and the possible role of small intestinal dysfunction such as bacterial overgrowth and malabsorption in the occurrence of symptoms in this disorder. PMID- 1748047 TI - Pelvic floor muscles response to graded rectal distension and cutaneous stimulation. AB - The responses of the external ani sphincter (EAS) and the levator ani (LA) muscles to graded rectal distension and to cutaneous and genital stimulation were examined in 25 cats of either sex. The animals were anesthetized with sodium pentobarbital (30 mg/kg, intraperitoneal) and then tested in two positions: with hindlimbs extended and with hindlimbs flexed simulating the straining position. Graded rectal distension was performed at two speeds: 1 and 10 sec. Basal levels of activity in the EAS were higher in the straining than in the extended position (P less than 0.005). The EAS responded to rapid rectal distension with inhibition of its activity. When changed to the straining position significant increases in muscular activity were observed after 35 cc of balloon insufflation (P less than 0.005). In the same muscle, slow distension produced an initial decrease in activity followed by significant increases after insufflation of 40 cc in the extended position and of 30 cc in the straining position. Basal activity in the LA was similar in both positions tested. The main effects of rectal distension in this muscle were increases in activity, significant only after high volumes of air inflation in the straining position (P less than 0.0001). Cutaneous stimulation disclosed a receptive field that was widespread for the EAS, extending over lumbosacral dermatomes (L3-S2), but greatly restricted for the LA. Responses to vaginal and cervical stimulation were more reliably obtained from the LA (P less than 0.001). These differences indicate that the EAS and LA muscles of the cat correspond with distinct, although related neural circuits. PMID- 1748048 TI - Portal hypertensive colopathy. A new entity. AB - The aim of this paper was, first, to show in a case control study that in alcoholic cirrhotic patients colonic vascular ectasias (VE) are a complication of portal hypertension and, second, to establish in a histomorphometric study that colonic vascular ectasias and rectal varices (RV) are only endoscopic features of a new entity: portal hypertensive colopathy, the pathologic basis of which is colonic mucosal capillary ectasia. In the case control study, for each case, three age- and sex-matched controls selected from consecutive patients were used. Sixteen alcoholic cirrhotic patients, 12 men, 4 women (mean age +/- SD: 62 +/- 10 years) had colonic vascular ectasias. The prevalence of esophageal varices (88% vs 44%, P less than 0.005), esophageal varices (greater than or equal to 5 mm) (44% vs 12.5%, P less than 0.01), previous history of bleeding from esophageal varices (44% vs 8%, P less than 0.005), and rectal varices (63% vs 6%, P less than 0.001) was significantly greater in cases with colonic vascular ectasias than in controls without colonic vascular ectasias. The relative risk of colonic vascular ectasias in alcoholic cirrhotic patients with esophageal varices versus cirrhotic patients without esophageal varices was 14.4 (95% confidence interval 2.8-75.3). In the histomorphometric study, cirrhotic patients with vascular ectasias and/or rectal varices had a significantly higher mean diameter of vessels (20.3 +/- 1.5 microns vs 18.7 +/- 1.6 microns, P less than 0.05) and a higher mean cross-sectional vascular area (2143 +/- 396 microns 2 vs 1676 +/- 345 microns 2, P less than 0.05) than cirrhotic patients without vascular ectasias and/or rectal varices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748049 TI - Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis. AB - Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic. Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography. There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points. Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic. The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora. This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection. PMID- 1748050 TI - Hepatotoxicity from paraaminobenzoic acid. PMID- 1748051 TI - Gallstone ileus successfully treated by shock-wave lithotripsy. PMID- 1748052 TI - Cyst of the gallbladder. AB - A cyst of the gallbladder is a very rare lesion. The possible causes of such an anomaly are reviewed. It may be acquired or congenital. The latter is particularly exceptional. A case of congenital cyst is reported and illustrated by various imaging techniques. PMID- 1748053 TI - Renal factors influencing blood pressure threshold and choice of treatment for hypertension in IDDM. AB - In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (less than 45 yr of age), average mean +/- SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was approximately 90.0 +/- 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between approximately 105 and approximately 95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml.min-1.mo-1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: greater than 95 mmHg for the start of progression of microalbuminuria and greater than 105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of approximately 90-95 mmHg and only a limited fall in GFR with MAP of approximately 100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording. PMID- 1748054 TI - Factors influencing threshold and choice of treatment for hypertension in NIDDM. Cardiovascular factors. AB - In nondiabetic populations, there is an approximately 40% increase in stroke risk and a 25% increase in coronary heart disease (CHD) risk with every 6-mmHg increase above 75 mmHg in usual diastolic blood pressure. Diabetes increases the risk of both conditions by two- to threefold, and in diabetic patients, hypertension further increases these risks. The benefits of lowering blood pressure in nondiabetic subjects have been subjected to meta-analysis, which has demonstrated benefits equivalent to 100% reversal of the excess risk for stroke but with only approximately 50% of CHD risk reversible after 2-3 yr of treatment. In these analyses, the benefit of treating diastolic blood pressure is similar at all levels greater than 90 mmHg. If these results are extrapolated to diabetic patients, possible benefits of therapy for mild hypertension could be two to three times greater than in nondiabetic subjects, but this could still correspond to 300 person-yr of treatment to prevent one nonfatal stroke and 2500 person-yr of treatment to prevent one CHD death, with treatment that may deleteriously affect quality of life in 36% of all diabetic patients. There may also be risks in treating patients with mild hypertension who have existing CHD or left ventricular hypertrophy, which are more common in diabetes. Despite the theoretical risk of deleterious changes in several cardiovascular risk factors with thiazides or beta-blockers, most of the newer agents have not yet been demonstrated to produce similar benefits to the large prospective studies in which the aforementioned agents have been used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748055 TI - Relationship between insulin resistance and hypertension. AB - Patients with hypertension have been shown to be resistant to insulin-stimulated glucose uptake and to be both hyperinsulinemic and hypertriglyceridemic compared with matched normotensive control groups. These abnormalities are present before the institution of antihypertensive therapy and do not necessarily improve when blood pressure is effectively lowered. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and high blood pressure can be produced in fructose-fed Sprague-Dawley rats, but the development of these changes is inhibited by exercise training or somatostatin infusion. Furthermore, insulin-stimulated glucose uptake is lower in spontaneously hypertensive rats (SHRs) than Wistar Kyoto rats, and this is associated with higher plasma triglyceride concentrations and blood pressure. In addition, a defect in insulin-stimulated glucose uptake can be shown in adipocytes isolated from SHRs, and the greater the degree of in vitro insulin resistance, the higher the plasma insulin concentration and blood pressure. These data strongly support the view that abnormalities of insulin and lipid metabolism are associated with high blood pressure in both patients and rodent models of experimental hypertension. In the latter context, endogenous hyperinsulinemia and hypertriglyceridemia are risk factors for coronary heart disease. The fact that antihypertensive treatment has not focused on correcting these metabolic abnormalities may explain why it has been difficult to show that lowering blood pressure decreases the risk of coronary heart disease. It can be argued that abnormalities of carbohydrate and lipoprotein metabolism play a role in both the etiology of hypertension and the clinical course of hypertensive patients. PMID- 1748056 TI - Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors. AB - In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension. PMID- 1748057 TI - Introduction: hypertension and diabetes. Critical combination for micro- and macrovascular disease. PMID- 1748058 TI - Epidemiology of hypertension in diabetic patients and implications for treatment. AB - We review the epidemiology of hypertension in diabetic patients and discuss the implications for treatment. The relationship between coronary heart disease (CHD) mortality and blood pressure (BP) in the World Health Organization Multinational Study of Vascular Disease in Diabetics (WHO MSVDD) is evaluated. One thousand two hundred seventy-seven patients with insulin-dependent diabetes mellitus (IDDM) and 3463 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 35 55 yr at baseline, from 10 centers throughout the world were evaluated. CHD mortality after a follow-up of 6-7 yr was measured. Estimates of usual diastolic BP were made with data from the Framingham study. The relative risk (RR) of CHD death was plotted against usual diastolic BP for IDDM and NIDDM, and the shapes of the relationship were compared with a meta-analysis of nine prospective studies in nondiabetic populations. For the NIDDM group, the CHD RRs were significantly greater than 1.0 only for the uppermost diastolic BP category (RR 2.23, 95% confidence interval 1.14-4.40). For the IDDM group, the shape of the diastolic BP-CHD relationship was difficult to assess in view of the small number of events. In neither diabetic group was the evidence for a J-shaped relationship. Elevated BP is associated with increased cardiovascular/renal mortality in both types of diabetes. However, the efficacy of antihypertensive therapy in the prevention of these outcomes remains unclear. Prospective data from the WHO MSVDD do not provide clear evidence of benefit from treating diastolic BP less than 95-100 mmHg in NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748059 TI - Islet cell antibody reactivity with human fetal pancreatic islets. AB - To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9/14 pancreata and all (9/9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted. PMID- 1748060 TI - Diabetes-related renal growth and IGF-I accumulation in castrated rats. AB - The effects of castration on diabetes-related renal growth and IGF-I regulation were studied. In the rat, prepubertal castration is associated with a normal or increased surge in plasma insulin-like growth factor I (IGF-I) at the time of 'puberty'. In order to determine the role of sex steroids in the development of diabetes-related kidney growth and IGF-I regulation, Sprague-Dawley rats were castrated at the age of 4 weeks and streptozotocin diabetes was induced at the age of 13 weeks. The development of renal enlargement and kidney IGF-I levels was studied over the following 7 days. Kidney weight in diabetic animals was significantly greater than in controls, and by day 7, had increased by 27% (1.20 +/- 0.03 vs 0.94 +/- 0.03 g, P less than 0.001). Kidney IGF-I content was significantly elevated in diabetic rats, peaking on day 1 (diabetic, 1159 +/- 302 ng/g vs control, 237 +/- 53 ng/g, P less than 0.001) and remaining higher than control levels throughout the 7 days of the experiment. The pattern of diabetes related kidney growth and IGF-I regulation in castrated rats resembles that of age matched intact postpubertal controls, suggesting that sex steroids do not have a direct role in these phenomena. PMID- 1748061 TI - In vitro retinal and erythrocyte polyol pathway regulation by hormones and an aldose reductase inhibitor. AB - The effects of a high-glucose medium, insulin, and an aldose reductase inhibitor (ONO-2235) on sorbitol accumulation were compared in the human erythrocyte and the rabbit retina, while the effects of epinephrine on in vitro sorbitol accumulation were investigated in the human and rabbit retina. In both erythrocytes and the retina, linear increments of sorbitol accumulation were observed in a dose-dependent manner with 5 to 50 mM glucose. These increments were markedly inhibited by 100 microM ONO-2235 but not by insulin (400 microU/ml). In the presence of 5 mM glucose, a dose-dependent increase of the sorbitol content of the rabbit retina was seen following epinephrine stimulation (0.4-4.0 microM and this was markedly reduced by 100 microM ONO-2235. Moreover, both 50 mM glucose and 4.0 microM epinephrine increased the sorbitol content of the retina from a diabetic patient, and the glucose-induced increment in sorbitol was significantly reduced by 100 microM ONO-2235. Our data suggested that aldose reductase inhibitors might be useful for the treatment of diabetic retinopathy, since the polyol pathway appears to be an important factor in its pathogenesis, and that catecholamines might have some role in the activation of the retinal polyol pathway. PMID- 1748062 TI - Low-dose octreotide is able to cause a maximal inhibition of the glycemic responses to a mixed meal in obese type 2 diabetic patients treated with insulin. AB - Short-term studies have shown that octreotide, a long-acting somatostatin analog, blunts postprandial glycemic responses and reduces insulin requirement in insulin treated diabetic patients. The aim of our study was to investigate the effects of three single, different doses of octreotide on the glycemic response to a mixed meal in eight insulin treated type 2 diabetic patients after secondary failure with hypoglycemic agents. Previous treatments were substituted by regular insulin, 0.5 U/kg/day divided into three sc injections, for at least seven days. All patients received: (a) regular insulin (0.1 U/kg, sc) at 7.30 am; (b) octreotide 25 micrograms sc or (c) 50 micrograms sc or (d) 100 micrograms sc simultaneously with insulin but injected at different sites. From 8.00 to 8.15 the patients consumed a preconstituted fluid mixed meal of 250 ml. Following insulin alone a significant increase in blood glucose levels was observed after the meal. Abolished and not significantly different blood glucose responses to the meal after each of the three doses of octreotide were observed. Our findings suggest that with a low dose of octreotide (25 micrograms) it is possible to abolish the postprandial glycemic peak in type 2 diabetic patients treated with insulin. PMID- 1748063 TI - Insulin resistance and action in hypertriglyceridemia. AB - To define further the characteristics of insulin insensitivity associated with hypertriglyceridemia, the metabolic responses to the euglycemic insulin clamp were evaluated in 6 hypertriglyceridemic male patients and compared to 5 normal male controls. At baseline, the hypertriglyceridemic patients had elevated triglycerides (687 +/- 172 vs 78 +/- 7 mg/dl, P less than 0.005) and free fatty acids (702 +/- 36 vs 444 +/- 42 microM/l, P less than 0.005) concentrations. During the euglycemic insulin clamp, steady-state plasma glucose concentrations were similar in both groups (90.2 +/- 1.5 vs 88.8 +/- 2.3 mg/dl, ns) as were steady state insulin levels (142 +/- 10.1 vs 132.2 +/- 6.8 microU/ml**). The amount of glucose metabolized during the last hour of the clamp (M) was significantly reduced in the hypertriglyceridemic patient (2.9 +/- 0.4 vs 6.2 +/- 0.7 mg.min-1.kg-1, P less than 0.001). Changes in free fatty acid, glycerol, B hydroxybutyrate, lactate and pyruvate during the euglycemic insulin clamp were similar indicating a preserved antilipolytic, antiketogenic and glycolytic intermediate (lactate + pyruvate) response to insulin and glucose infusion in the hypertriglyceridemic patients. In summary, hypertriglyceridemia is associated with insulin resistance as it relates to muscle glucose utilization. However, this is not universal, as a number of other insulin responsive pathways appear to be unaffected. PMID- 1748064 TI - One-year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy. AB - A double blind placebo controlled trial was performed to evaluate the effects of the aldose reductase inhibitor, ponalrestat, on symptomatic diabetic neuropathy. After a 4-week placebo run-in phase, 60 patients were 2:1 randomized to receive either 600 mg ponalrestat or placebo once daily over 12 months. Forty-six patients, 30 of whom were treated with ponalrestat and 16 with placebo, completed the study. Motor and sensory nerve conduction, thermal and vibration sensation thresholds, heart rate variation at rest, E/I ratio, pupillary dilation velocity and pupillary reflex latency were determined at baseline and after 6 and 12 months. Neuropathic symptom scores were assessed every 3 months. Among the fifteen nerve function parameters studied, only trends in favour of ponalrestat were noted for heart rate variation and E/I ratio after 6 months (P = 0.06), but no significant differences between the groups could be demonstrated during the study. No adverse reactions were observed. It is concluded that one-year treatment with ponalrestat has no beneficial effects on symptoms or electrophysiological parameters in diabetic neuropathy. PMID- 1748065 TI - Correlation of glycosylated hemoglobin measured by affinity vs ion exchange chromatography with mean blood sugar in pediatric IDDM patients. AB - Affinity chromatography provides a more specific estimate of glycosylated hemoglobin (GlyHb) than does ion exchange chromatography (HbA1). However, whether GlyHb correlates closer than HbA1 with mean blood glucose has not been established. GlyHb and HbA1 were measured in pediatric IDDM patients attending a clinic (n = 285 visits) over a one year period and correlated with the mean of a patient's blood glucose measurements from records of home blood glucose monitoring. Mean GlyHb was higher than mean HbA1 (10.8% vs 9.6%) as was its standard deviation (2.2% vs 1.5%). While both GlyHb (r = 0.75) and HbA1 (r = 0.65) were strongly correlated with estimates of mean blood glucose, the correlation with GlyHb was significantly stronger than with HbA1 for the entire spectrum of metabolic control (P = 0.03), as well as for a segregated group of 'poorly controlled' patients with mean blood glucose greater than 150 mg/dl (P = 0.04). The results suggest that GlyHb is more accurate than HbA1 for estimating metabolic control and that GlyHb shows greater discriminating power than HbA1, especially at high concentrations of blood sugar. The mean blood glucose can be estimated from the equation: mean blood glucose (mg/dl) = (11.3 x GlyHb) + 32. PMID- 1748066 TI - Activation of erythrocyte aldose reductase in man in response to glycaemic challenge. AB - Flux via the polyol pathway, which comprises the enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH), has been implicated in the debilitating complications of diabetes. Previous studies in this laboratory have indicated that erythrocyte AR activities are increased (by 72%) in insulin-dependent diabetic patients. To investigate the mechanism underlying this activation, the response of AR activity to oral glucose challenge was investigated in eight overnight-fasted human volunteers. Glucose consumption led to a transient activation (by 76%: P less than 0.01) of erythrocyte AR, which paralleled the rise and subsequent fall in blood glucose concentrations. It is concluded that erythrocyte AR activity is acutely modulated in response to hyperglycaemia by an as yet unknown mechanism. PMID- 1748067 TI - [The selection of spongiosa donors for a bone bank]. AB - A prospective trial was carried out in 156 unselected patients (41 men, mean age 67.5 years, 115 women, mean age 71.4 years) who had undergone total hip joint replacement because of degenerative or inflammatory arthritis or fracture of the neck of the femur. The excised femoral heads were subjected to three-stage bone bank screening so as to ascertain how many of them would pass the clinical, biochemical and microbiological exclusion criteria. Only 26 out of 156 femoral heads (17%) proved to be acceptable for the bone bank. Ninety patients (58%) were excluded on clinical grounds such as old age (over 80 years), malignant neoplasms, rheumatoid arthritis, previous intraarticular injections or long-term steroid medication. Positive hepatitis serology excluded 19%, and raised preoperative neopterin concentration excluded 25%, though three months postoperatively this was confirmed in only 2%. Routine neopterin assay seems to be a useful step towards improved bone bank screening, since neopterin concentration is clearly increased in recent virus infections such as HIV. Bacterial contamination was of no practical importance. Because of the low proportion of femoral heads passed as suitable for the bone bank, the existing exclusion criteria will have to be critically scrutinized, and alternative procedures for harvesting bone safe for transplantation (freeze drying, autoclaving, irradiation) will have to be employed. PMID- 1748069 TI - [A fistula between the rectosigmoid junction and the ileum as a complication of highly malignant AIDS-associated lymphoma]. AB - A 29-year-old man, a known heroin addict until 1984 in whom HIV antibodies had been first demonstrated in 1985, was hospitalized because of fever, nocturnal sweating, weight loss and treatment-resistant diarrhoea. An opportunistic infection of the gastrointestinal tract was excluded microbiologically and serologically. Coloscopy and biopsy revealed a highly malignant gastrointestinal B-cell lymphoma, which had caused a spontaneous rectosigmoid-ileum fistula. Lymphoma infiltrations were also found in the duodenum, jejunum, left lung and brain. Because the underlying disease was far progressed (CD4/CD8 ratio: 0.04) and the patient was in a poor general condition neither surgery nor chemotherapy was undertaken. He died of cerebral lymphoma involvement. Gastrointestinal lymphoma should be included in the differential diagnosis of chronic diarrhoea in HIV-positive patients. PMID- 1748068 TI - [Pacemaker syndrome with AV-synchronized stimulation of the heart]. AB - Characteristic signs of the pacemaker syndrome occurred in a 69-year-old woman with intermittent 3 degrees atrioventricular (AV) block after implantation of a dual-chamber AV-synchronized pacemaker. Cannon beats due to inappropriate atrial timing were the main haemodynamic finding. Their development and size depended on the programmed AV interval and AV-synchronized mode of stimulation. Very long AV intervals in the DDD mode at a heart rate of 100/min caused very unpleasant palpitations and pulsations in the upper thorax. The symptoms due to the cannon beats were avoided by changing to a short AV interval. The clinical and haemodynamic events were thus the consequence of preserved sinus node function with subsequent atrial triggering. PMID- 1748070 TI - [The antibiotic therapy of community-acquired pneumonias]. PMID- 1748071 TI - [Hormonal therapy of breast carcinoma in women]. PMID- 1748072 TI - [Insulin--a side issue or indeed the cause of hypertension?]. PMID- 1748073 TI - [Liver biopsy]. PMID- 1748074 TI - [A paranoid syndrome after discontinuing tuberculostatics]. PMID- 1748075 TI - [Propranolol in portal hypertensive gastropathy]. PMID- 1748076 TI - Influence of the fiber length on the power spectra of single muscle fiber extracellular potentials. AB - Influence of the fiber length on the power spectra of the single muscle fiber extracellular action potentials (SMFEAPs) as well as on the spectral changes under alterations in the propagation velocity (v) and intracellular action potential duration (Tin) was studied theoretically for a fiber-electrode distance typical of surface recordings. It was shown that the magnitude and distribution of the SMFEAP spectral power depend on the fiber length. The shorter the fiber, the wider the frequency region in which the total spectral power is distributed and the smaller the spectrum max amplitude. The fiber length affects the spectrum changes that are due to alterations in v or Tin, and, consequently, the spectrum characteristic frequencies--Fmax, Fmed and Fmean, as well as the total spectral amplitude (TSA) and total power (TP). Whereas for a relatively long fiber Fmax depends linearly on v and Fmed and Fmean increase with v increasing, for a short fiber the linearity of the relation between Fmax and v can be disturbed, and Fmed and Fmean can decrease with v increasing. Under the condition of a relatively short fiber, a change in Tin can cause changes not only in Fmed and Fmean, but in Fmax as well. It was shown, that as a result of the finite length of the muscle fibers as well as of the asymmetry of the end-plate location in relation to the fiber ends, dips can be observed in the spectrum even in a case of monopolar recording. Positions of the dips in the power spectra depend on propagation velocity. PMID- 1748077 TI - Electromyographic study of facial expressions during pathological laughing and crying. AB - We studied facial expressions during pathological laughing and crying in 6 patients using EMG investigation. Increased EMG discharges of M. frontalis and M. corrugator supercilii are characteristic of pathological laughing and crying in addition to an increase of EMG discharges of M. orbicularis oculi, M. levator labii superiors, M. zygomaticus major, M. risorius and M. mentalis which we observed during natural laughing. Its patterns of facial expressions are similar to that of crying in normals. From the fact that normals show the same expression of laughing and crying in an extreme emotional outburst, we speculate that pathological laughing and crying is maximal manifestations of facial expressions caused by a release phenomenon of the upper center. PMID- 1748078 TI - Reversal of long-latency reflexes in first dorsal interosseous during a force tracking task. AB - Cutaneous reflexes in response to electrical stimulation of the index finger were recorded from first dorsal interosseous (1DI) at specified force levels under three conditions: during a static posture and during the incremental and decremental phases of a sinusoidal, force-tracking task. Under static conditions, while 1DI generated a steady force [10, 20 or 30% maximum voluntary contraction (MVC)], four reflex components could be identified: E1, I1, E2 and I2. The amplitudes of these components were measured as the subjects tracked a 0.5 Hz sine wave by gradually changing the force output of 1DI between zero and 40% MVC. E1 and I1 showed minimal changes from the static condition, while activity during the E2 period was inhibitory during the incremental phase and excitatory during the decremental phase of tracking. Abrupt switching from inhibition to excitation during the E2 period occurred around the transition from incremental to decremental force. Activity during the I2 period was less markedly modulated than that during E2. Reflex reversal during the E2 interval may function to reduce the rate of change of force under conditions requiring precise force-control. PMID- 1748079 TI - Premovement silence of EMG activity prior to movement in Parkinson patients. AB - Premovement silence (PMS) of tonic agonist electromyographic activity (EMG) preceding a maximum effort elbow extension was studied in eight bradykinetic Parkinson patients. The occurrence and duration of PMS have been shown to be significantly correlated with peak acceleration of movement in normal subjects. To determine if inability to silence the EMG prior to the initial agonist burst may contribute to bradykinesia of Parkinson's disease, patients maintained elbow extension against a tonic load on triceps, and in response to a tone performed a maximum effort elbow extension. All eight patients showed some trials (mean = 30%) with PMS. However, neither the incidence of PMS nor its duration were significantly correlated with mean peak acceleration. A significant correlation was found between the incidence of abnormal initial agonist bursts, called "segmented bursts," and mean peak acceleration. We conclude that ability to silence the agonist muscle prior to movement is not strongly associated with bradykinesia in Parkinson's disease. PMID- 1748080 TI - Elbow torques and EMG patterns of flexor muscles during different isometric tasks. AB - This paper examines the torque responses and EMG activity levels in four muscles acting at the elbow joint during different combinations of one- and two- degree of freedom isometric torque production (single and dual tasks, respectively). Flexor and supinator/pronator torques and surface EMG signals from m. biceps brachii, m. brachialis, m. brachioradialis and m. triceps brachii were measured in 16 male subjects while they performed maximal effort isometric contractions of pure flexion, pure supination, pure pronation, combined flexion and supination and combined flexion and pronation. In the single tasks, the torque responses were consistent with task requirements, but the dual task results were surprising in that flexor torque levels were reduced as compared to pure flexion, while supinator/pronator torque levels were as high or higher than in pure supination or pronation. Muscle activity levels varied with task, and could not always explain the differences observed in torque responses. These data are discussed within the framework of subpopulations of task-specific motor units within each muscle. The implications of such task-specific muscle units are related to musculoskeletal modelling and previous EMG - torque relationships found at the elbow. PMID- 1748082 TI - Presentations from the twenty-second annual meeting of the Environmental Mutagen Society. April 6-11, 1991. PMID- 1748081 TI - Workshop overview: new molecular techniques in genome analysis. AB - An overview of the application of various molecular techniques to the analysis of genomic DNA is presented. For the analysis of small-scale changes, the polymerase chain reaction (PCR), colony probe hybridization, mismatch hybridization, and denaturing gradient gel electrophoresis (DGGE) are providing information on mutations within prokaryotic and eukaryotic genes. For large-scale changes, fluorescence in situ hybridization (FISH), pulsed-field gel electrophoresis (PFGE), Southern blotting, multiplex PCR, hybridization of linked probes, and restriction enzyme mapping are permitting analysis of genomic alterations that are larger than point mutations but below the resolution of standard cytogenetic analysis. Many of these techniques, either alone or in combination, produce DNA that can be subjected to DNA sequence analysis, which provides the most detailed information regarding genomic changes. PMID- 1748083 TI - Analysis of Salmonella typhimurium hisD3052 revertants: the use of oligodeoxyribonucleotide colony hybridization, PCR, and direct sequencing in mutational analysis. AB - A rapid method for determining the DNA sequences of Salmonella typhimurium hisD3052 revertants is presented. DNA colony hybridization was used to analyze revertants previously studied by Isono and Yourno [Proc Natl Acad Sci USA 71:1612 1617, 1974]. Synthetic oligodeoxyribonucleotide probes (18-mers) were able to distinguish sequences that differed by a single base pair. Mutant his sequences not identified by probing analysis were amplified using polymerase chain reaction (PCR) and directly sequenced. The combined use of DNA-colony hybridization and direct sequencing offers a precise and rapid means for the molecular characterization of hisD3052 revertants. PMID- 1748084 TI - Rapid localization of point mutations in PCR products by chemical (HOT) modification. AB - Our studies of mutational mechanisms in mammalian cells use the AS52 Chinese hamster ovary cell line. AS52 mutants can be selected as 6-thioguanine resistant colonies and mutations are studied at a chromosomally integrated gpt locus. Mutant gpt sequences are amplified using the polymerase chain reaction (PCR) to distinguish deletions from putative point mutations. PCR is efficiently performed from a few thousand lysed cells or from isolated genomic DNA. Amplified mutant PCR fragments carrying putative point mutations are further characterized by localizing the site of the mutation using chemical modification. A heteroduplex molecule consisting of one wild-type and one mutant DNA strand is generated. A base mismatch will be produced at the site of the mutation. Mismatched cytosine or thymine residues are sensitive to modification by hydroxylamine or osmium tetroxide, respectively. The modified DNA heteroduplex is then sensitive to piperidine cleavage. If one strand is 32P-end labeled, then the cleavage product can be separated on a denaturing acrylamide sequencing gel and visualized using autoradiography. Thus, the site of a mutation can be localized to a specific region of the gene, thereby simplifying the DNA sequence analysis and facilitating the rapid generation of mutational sequence spectra. PMID- 1748085 TI - Use of PCR amplification of cDNA to study mechanisms of human cell mutagenesis and malignant transformation. AB - PCR is widely employed to amplify short segments of genomic DNA to determine if a specific change has occurred. But some investigators need to sequence the entire coding region of mammalian genes to determine what specific changes have occurred. In 1989, we [Yang et al: Gene 83:347-354] described a method to copy mRNA of the hypoxanthine (guanine) phosphoribosyl transferase (HPRT) gene directly from the lysate of a clone of 6-thioguanine-resistant mutant diploid human fibroblasts without the need for RNA extraction or DNA template purification. To avoid detecting random changes introduced by polymerases, 100 to 500 cells from an individual clone, each containing the identical mutation, are lysed and the cDNA is amplified 10(10)-to 10(11)-fold to obtain 5 to 10 micrograms of DNA. The consensus sequence of the cDNA is determined by direct nucleotide sequencing. Using this method, we have investigated the kinds of mutations induced by carcinogens in the coding region of the HPRT gene and their location in the gene and examined the role of DNA repair in this process. Normal repair-proficient human cells and cells deficient in DNA repair were exposed to mutagens in exponential growth or synchronized and exposed at the beginning of S phase or in G1 phase several hr prior to DNA replication. The kinds and location of mutations in the HPRT gene were determined and knowledge of the nature of the DNA lesions formed by the various mutagens allowed assignment of the DNA strand in which the premutagenic lesion that gave rise to the mutation had been located. Related assays involving PCR have been used to determine the nature of mutations in the coding region of the H-, N-, or K-ras genes of tumor-derived malignant human cells and to determine whether or not such cells express specific growth factor genes. PMID- 1748086 TI - Analysis of mutations using PCR and denaturing gradient gel electrophoresis. AB - Denaturing gradient gel electrophoresis (DGGE) separates DNA molecules based on primary sequence. Under the appropriate conditions, all base pair (bp) substitutions, frame-shifts, and deletions less than about 10 bp can be resolved from the wild type sequence using DGGE. Polymerase chain reaction (PCR) permits facile amplification of a given region of the genome. We have combined PCR and DGGE to: (i) Localize mutations in the X-linked human androgen receptor gene. PCR/DGGE was used to screen the individual exons in the 2757-bp coding region of the gene in afflicted individuals as well as in potential carriers. Inheritance of a mutant allele has been demonstrated in several cases; (ii) Analyze thousands of thioguanine-resistant mutants simultaneously. The in vitro mutational spectra of MNNG, ICR-191, and cisplatin at the human HPRT locus have been examined by this method. The compounds all have mutational hotspots in a GGGGGG sequence in exon 3; however, the particular mutations induced by the agents were different; (iii) Examine the fidelity of several DNA polymerases used in PCR. The fidelity of Thermus aquaticus DNA polymerase (Taq) is 1-2 x 10(-4) misincorporations/bp/replication. Problems with Taq polymerase arise in the analysis of complex mutant populations by DGGE because the Taq-induced errors reduce the sensitivity of the system. To circumvent this, it had been necessary to use Sequenase, a modified T7 DNA polymerase with a higher fidelity. However, Sequenase is not thermostable and must be added every PCR cycle. A thermostable DNA polymerase from Thermococcus litoralis (Vent) is now available, and we have examined the fidelity of Vent, Taq, and Sequenase polymerase in PCR using DGGE. The fidelity of Vent, Taq, and Sequenase polymerase was 2.4 x 10(-5), 8.9 x 10( 5), and 4.4 x 10(-5) errors/bp, respectively. Vent polymerase had the highest fidelity of the three enzymes tested. PMID- 1748087 TI - A molecular geneticist's view of complex genomic lesions. AB - Molecular genetic techniques have been used effectively to study the DNA lesions, many of which are large and complex, that are responsible for human genetic disease. In this workshop we explore some of these techniques, how they are applied to study genetic lesions, and how they may be applied to the needs of genetic toxicology. PMID- 1748088 TI - DNA sequence mapping by fluorescence in situ hybridization. AB - Various types of DNA probes, such as total genomic DNA, repetitive sequences, unique sequences, and composites of chromosome-specific DNA probes, can be used with fluorescence in situ hybridization (FISH) techniques to address research questions having to do with localization, mapping, and distribution of DNA in situ. FISH involves the formation of a heteroduplex between such DNA probes and chromatin targets on a microscope slide, which can be visualized with fluorescent reporter molecules. Three chromatin targets--metaphase chromosomes, somatic interphases, and zygote interphases--offer increasingly extended states of chromatin which can be strategically selected, individually or in combination, to address specific research questions of interest. PMID- 1748089 TI - Analysis of human HPRT deletion mutations with X-linked probes and pulsed field gel electrophoresis. AB - Because the human hprt gene is used in numerous mutation studies, it is important to fully characterize this gene. Therefore, our laboratory has undertaken to map the region around the hprt gene at band q26 of the human X chromosome. Utilizing hprt mutant T-cell clones isolated using the hprt clonal assay, which have deletions of all or part of the hprt gene, we have ordered 5 anonymous probes previously known to map in Xq26. Results suggest that this region includes between 460 kb and 18 Mb of DNA, which is at least 10 times the size of the hprt gene itself (43 kb). Pulsed field gel analysis of the region is underway to determine the exact distances between each of the anonymous probes and hprt and to determine deletion sizes in the mutant T-cell clones. PMID- 1748090 TI - Direct DNA sequencing of PCR products. AB - Experiments are described which elucidate some of the technical problems associated with the direct sequencing of polymerase chain reaction (PCR) amplified DNA. Sequencing primer purity, labeling methodology, and template preparation were explored. Conditions are presented for the routine sequencing of single- and double-stranded PCR products. PMID- 1748091 TI - Micronuclei as an index of cytogenetic damage: past, present, and future. AB - The workshop was designed to present what is known about the production of micronuclei, what protocols are now accepted or proposed internationally, what new results have been obtained, and what new methods and protocols are likely to be forthcoming. This report is designed to convey the flavour of the workshop and to provide the essence of the new information. After the workshop an effort was made to determine what single protocol would satisfy the requirements set for the micronucleus test by as many regulatory agencies as possible. The result, reported here, includes the requirements of six regulatory authorities in Canada, the European Economic Community, the Organization for Economic Co-operation and Development, Japan, and the United States. PMID- 1748092 TI - Overview: industrial perspectives on existing in vivo gene mutation assays. AB - In vivo gene mutation assays are considered the most definitive for the evaluation of human health risks. Suggestions are provided here for the critical evaluation of the application of established in vivo gene mutation assays and alternative approaches in the evaluation of industrial chemicals. Objective evaluation of the assays and approaches based on sound science and practical issues will allow better application of the existing assays. Such an evaluation may also help illuminate areas of improvement, as well as help guide the development of future assays. PMID- 1748093 TI - EPA use of in vivo germ cell mutagenicity data. AB - The Toxic Substances Control Act (TSCA) provides the U.S. Environmental Protection Agency, Office of Toxic Substances (EPA, OTS) with the authority to regulate chemical use by requiring testing and use restrictions as appropriate to protect human health. Regulation on the basis of heritable mutation induction is specifically mentioned in the Test Rule section of the law and has also been pursued for new chemical substances. A tiered scheme of mutagenicity testing has been employed and recently revised to assess mutagenicity hazard. In vivo assay systems play key roles at all three levels in the scheme, beginning with the first level of determining intrinsic mutagenicity hazard. Once intrinsic mutagenicity has been identified, the revised scheme requires an assay or assays to assess chemical interaction with gonadal DNA. Finally, the scheme contains tests that permit risk assessment for a chemical. The recently-revised Office of Pesticide Programs (OPP) mutagenicity testing requirements closely parallel those of OTS. PMID- 1748094 TI - Factors that affect the molecular nature of germ-line mutations recovered in the mouse specific-locus test. AB - The morphological specific locus test (SLT), which allows the scoring of 2,000 loci/hr/person, has been in use for four decades for measuring mammalian germ line mutation rates under various conditions of exposure. More recently, the SLT's capabilities for the qualitative characterization of mutations have been exploited. The large sets of mutations centered on specific loci that have been accumulated over the years, including sets of nested deletions, have provided prime material for fine-structure genetic analyses. Subsequent molecular entry to these regions has led to intensive physical/functional mapping of megabase segments of the genome. In turn, these investigations have generated genetic and molecular tools for analyzing individual mutations as to extent and nature of the genomic lesion. Using the results of such analyses, it has been shown that germ cell-stage at which mutagenic treatment is administered, rather than the nature of the mutagen used, may be the chief determinant of the nature of genomic lesions. These and related quantitative findings now make it possible to optimize conditions for the use of mutagens in providing desired types of mutations as tools (e.g., high incidences of deletions or other rearrangements vs. high incidences of point mutations). PMID- 1748095 TI - The biochemical specific-locus test and a new multiple-endpoint mutation detection system: considerations for genetic risk assessment. AB - The importance of studying the generation of mutations in mouse germ cells is emphasized, and the utility of the biochemical specific-locus test in detecting germinal mutations is described. All experiments performed to date using this test are listed. The relevance of dominant mutations to human genetic risk is also discussed. Finally, the value of using multiple tests for the study of in vivo germinal mutations is discussed, and the design for a new multiple-endpoint system is presented. PMID- 1748096 TI - Emerging technologies--the use of transgenic mice for assessing mutagenic potential in vivo. PMID- 1748097 TI - A perspective on measurement of mutations in vivo. AB - The development of transgenic mouse lines with target genes that are suitable for tissue-specific mutagenesis studies is an important contribution to the field of environmental mutagenesis. These models can accommodate many of the questions relating to metabolism, distribution and relative potency of mutagens as well as providing a more comprehensive system for the identification of mutagens. However, the lesions that the field has learned about methods, development and validation from the use of in vitro systems must be applied to the development and validation of transgenic models. PMID- 1748098 TI - Uniqueness of interval and continuous training at the same maintained exercise intensity. AB - The present study sought to evaluate the inconsistencies previously observed regarding the predominance of continuous or interval training for improving fitness. The experimental design initially equated and subsequently maintained the same relative exercise intensity by both groups throughout the program. Twelve subjects were equally divided into continuous (CT, exercise at 50% maximal work) or interval (IT, 30 s work, 30 s rest at 100% maximal work) training groups that cycled 30 min day-1, 3 days.week-1, for 8 weeks. Following training, aerobic power (VO2max), exercising work rates, and peak power output were all higher (9 16%) after IT than after CT (5-7%). Vastus lateralis muscle citrate synthase activity increased 25% after CT but not after IT. A consistent increase in adenylate kinase activity (25%) was observed only after IT. During continuous cycling testing the CT group had reduced blood lactate (lab) levels and respiratory quotient at both the same absolute and relative (70% VO2max) work rates after training, while the IT group displayed similar changes only at the same absolute work rates. By contrast, both groups responded similarly during intermittent cycling testing with lower lab concentrations seen only at absolute work rates. These results show that, of the two types of training programs currently employed, IT produces higher increases in VO2max and in maximal exercise capacity. Nevertheless, CT is more effective at increasing muscle oxidative capacity and delaying the accumulation of lab during continuous exercise. PMID- 1748099 TI - The effect of exercise intensity and duration on salivary immunoglobulin A. AB - Two experiments were performed to examine salivary immunoglobulin A (s-IgA) responses to varying levels of exercise intensity and duration. For experiment 1, 9 college men (mean age, SD = 23.56, 1.64 years) completed treadmill runs of 15, 30, and 45 min at approximately 60% of maximum oxygen consumption (VO2max). For experiment 2, 9 other college men (mean age, SD = 23.67, 2.0 years) ran for 20 min at approximately 50, 65 and 80% of VO2max. Unstimulated salivary samples were collected before, and immediately, 1 and 2 h after the exercise. Samples were assayed for s-IgA using an enzyme-linked immunosorbent assay. Mean s-IgA levels did not change significantly (P greater than 0.05) at any of the post-exercise collection times when compared to pre-exercise levels. The results of this investigation indicated that running at intensities of 50-80% of VO2max and for durations of 15-45 min did not affect s-IgA levels. PMID- 1748100 TI - Maximal peak torque as a predictor of angle-specific torques of hamstring and quadriceps muscles in man. AB - This study assessed the relationship between the isokinetic peak torque (PT) (speed of movement 1.05 and 3.14 rads-1) and the angle-specific torques (ASTs) at 0.26 and 1.31 rad of knee flexion in multiple contractions of the quadriceps and hamstrings in 70 individuals with a chronic anterior cruciate ligament (ACL) insufficiency and 78 individuals with a chronic medial collateral ligament (MCL) insufficiency in one knee. At every test speed, the Pearson product moment correlation coefficients (r) between the PT and ASTs were highly significant (P less than 0.001) in the uninjured knees (r = 0.61-0.93) as well as in the knees with ACL (r = 0.61-0.87) and MCL (r = 0.74-0.91) insufficiency. In addition, in both groups the majority of the correlation coefficients exceeded 0.80, which is generally regarded as the threshold for the relationship to be considered clinically significant. Furthermore, using regression analysis, both extremities showed completely non-systematic distribution of the residuals. It is concluded that in healthy knees or knees with ACL or MCL insufficiency, the predictability of ASTs from PT was good, and, therefore, that AST analyses may offer little additional information about thigh muscle function to that obtained from a simpler and more commonly used measurement, the PT analysis. PMID- 1748101 TI - Plasma noncholesterol sterols in male distance runners and sedentary men. AB - Plasma lathosterol concentration is taken to be an index of the rate of cholesterol synthesis and plasma concentrations of plant sterols just as campesterol and betasitosterol are taken to be indeces of cholesterol absorption efficiency. These noncholesterol sterols were measured in plasma from 14 male distance runners and 10 sedentary men. Plasma lathosterol concentration was 30% lower (P less than 0.02) and plasma betasitosterol concentration was 33% higher (P less than 0.02) in the runners compared to the sedentary men. Plasma concentrations of lathosterol and plant sterols were inversely and significantly (P less than 0.05) correlated in both the runners and the sedentary men. Plasma plant sterol concentrations were correlated positively and significantly (P less than 0.01) with plasma high density lipoprotein cholesterol (HDL-C) concentrations in the runners and sedentary men combined. These findings suggest that more efficient cholesterol absorption may lead to higher plasma plant sterol concentrations and may contribute to lower cholesterol synthesis rates, reduced concentrations of plasma lathosterol and higher plasma HDL-C concentration in distance runners. PMID- 1748102 TI - Electromechanical response times and muscle elasticity in men and women. AB - The purpose of this study was to compare the delay in performance attributable to muscle elasticity in men and women. A group of 11 active young men age (mean, SE) 21.9, 0.7 years, stature 1.780, 0.020 m, body mass 76.4, 3.2 kg and 11 women age 20.9, 0.4 years, stature 1.670, 0.020 m and body mass 61.9, 2.6 kg provided written informed consent and were recruited to the study. In response to an acoustic signal delivered via headphones, the subjects performed a plantar flexion movement of the preferred leg as quickly as possible. A seated position ensured that the knee of the subject was flexed at a right angle and that the shank was vertical. The ball of the foot was on a force platform which was used detect the onset of muscle tension and the heel rested on a pressure pad which was used to identify movement. Surface electrodes sensed electromyographic activity (EMG) in the soleus muscle. Force platform output was captured by a digital storage oscilloscope and recorded via a y-t pen recorder or subsequent analysis. A separate timer was used to determine total reaction time (TRT). Premotor time (EMGT) was taken to be the time interval from the delivery of the signal to change in EMG. Electromechanical delay (EMD) was the time interval between the change in EMG and movement and was subdivided into force time (FT) i.e. the time interval between EMG and the onset of muscle tension and elastic charge time (CT) i.e. the time interval between the onset of muscle tension and movement. The subjects performed ten trials and in most cases the mean of ten readings was used to determine TRT, EMGT, EMD, FT and CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748103 TI - The influence of metabolic alkalosis upon exercise metabolism in the thoroughbred horse. AB - Six thoroughbred horses exercised on a motorised treadmill on two separate occasions at a speed of 11 or 12 m.s-1 for up to 2 min. 4 h prior to exercise each horse was given a 21 test solution of sodium bicarbonate (NaHCO3; 0.6 g.kg-1 body mass) or a control solution of water by nasogastric intubation, the order of administration of the two solutions was randomised. Blood samples (n = 15) were obtained before and during the 4 h after intubation, during exercise and for 30 min after exercise. NaHCO3 ingestion resulted in changes in pre-exercise acid base status. The changes in blood lactate and base excess with exercise were greater after NaHCO3 administration; after 1 min of exercise in the case of lactate (P less than 0.05) and immediately after exercise in the case of base excess (P less than 0.05). Plasma ammonia levels were lower during (P less than 0.05) and immediately after (P less than 0.05) exercise following NaHCO3 ingestion. The peak change in plasma ammonia with exercise was also lower after NaHCO3 ingestion (P less than 0.05). Following exercise after NaHCO3 ingestion, five horses demonstrated lower muscle adenosine 5-triphosphate loss (P less than 0.05) and inosine 5-monophosphate formation (P = 0.05) and higher glycerol 3 phosphate formation (P less than 0.05). There is evidence to suggest that metabolic alkalosis may delay the onset of fatigue by decreasing the extent of adenine nucleotide loss during high-intensity exercise. PMID- 1748104 TI - The validation of backward extrapolation of submaximal oxygen consumption from the oxygen recovery curve. AB - The purpose of this study was to determine the validity and practicality of exponential vs linear backward extrapolation of the O2 recovery curve for prediction of exercise oxygen consumption (VO2). Eight men and women, age 20.1, 0.9 years, body mass 66.0, 2.5 kg (mean, SEM), completed seven bouts of cycle ergometer exercise at submaximal power outputs ranging from 50 to 175 W. Respiratory gases were collected from each subject during exercise and recovery. The monoexponential extrapolation of five recovery samples (r2 = 0.85) and linear extrapolation of one recovery sample taken during the first 20-s of recovery (r2 = 0.83) accounted for similar amounts of variance in predicting exercise VO2. The linear regression equation was the most practical predictor, as only one recovery gas sample was necessary and it did not require the complicated mathematical techniques used in exponential regression. PMID- 1748105 TI - Altered metabolic response of iron-deficient women during graded, maximal exercise. AB - Metabolic responses during a standardized, progressive, maximal work capacity test on a cycle ergometer were studied in 11 women, mean age 28 (SEM 2) years, at admission to the study, after their body iron stores were depleted by diet, phlebotomy and menstruation for about 80 days and after iron repletion by diet for about 100 days, including daily iron supplementation (0.9 mmol iron as ferrous sulfate) for the last 14 days of repletion. Iron depletion was characterized by a decline (P less than 0.05) in hemoglobin, ferritin and body iron balance. Iron repletion, including supplementation, increased (P less than 0.05) hemoglobin, ferritin and iron balance. No changes were observed in cardiovascular and ventilatory responses or peak oxygen uptake. Iron depletion was associated with a reduced (P less than 0.05) rate of oxygen utilization, total oxygen uptake and aerobic energy expenditure, and elevated (P less than 0.05) peak respiratory exchange ratio and post-exercise concentration of lactate. Reduction of body iron stores without overt anemia affects exercise metabolism by reducing total aerobic energy production and increasing glycolytic metabolism. PMID- 1748106 TI - Effects of carbohydrate loading and underwater exercise on circulating cortisol, insulin and urinary losses of chromium and zinc. AB - The effects of carbohydrate loading on relative stress responses of eight male subjects performing intermittent leg exercise at 80% maximum oxygen consumption during headout immersion in 25 degrees C water were tested. Carbohydrate loading increased the number of work cycles completed, with less physical stress compared with that completed following the control diet period. Pre-exercise serum cortisol values were similar on both diets prior to exercise but following exercise control values were greater (1152, 94 vs 858, 77 nmol l-1; mean, SEM). Chromium losses, which have been shown to correlate with stress, were lower during the carbohydrate loading period, 8.6, 1.3 vs 12.4, 2.0 ng h-1, and were correlated with post-exercise serum cortisol. Urinary zinc losses were also lower during carbohydrate loading, while urinary losses of potassium, magnesium and calcium remained constant. Insulin values decreased similarly following exercise in both groups and were not altered by carbohydrate loading. These data demonstrate that carbohydrate loading increases immersion exercise output with less stress as determined by serum cortisol and urinary chromium losses. PMID- 1748107 TI - Haemodynamic responses to nonhypotensive central hypovolaemia induced by lower body negative pressure in men and women. AB - Haemodynamic responses to low levels of lower body negative pressure (LBNP) were investigated in two groups of healthy, normotensive volunteers (8 men and 8 women) during two repeated experimental runs on two occasions, the latter determined by the different phases of the menstrual cycle in the women. The data consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP), pulse rate (fc), forearm blood flow (FBF) and forearm vascular conductance (FC). The resting cardiovascular status was similar in men and women, except that women had a significantly higher fc than men. LBNP (1.3, 2.7 and 4 kPa) had no significant effect on any BP variable or on fc. However, FBF and FC were reduced at all levels of LBNP. Significant overshoots in FBF and FC were seen in all subjects following the release of LBNP of 2.7 and 4 kPa and, in most cases, after release of LBNP of 1.3 kPa. There were no significant gender differences in any of the responses to LBNP. Furthermore, none of the cardiovascular variables measured showed significant differences between the follicular and luteal phases of the menstrual cycle in women, either at rest or during exposure to LBNP, and the responses in the men on the two occasions were not different. These findings indicate that gender differences in responses to LBNP hypothesized previously are not apparent during and after exposure to low levels of LBNP. PMID- 1748108 TI - Effects of sleep disturbances on subsequent physical performance. AB - The purpose of the study was to compare the cardiovascular, respiratory and metabolic responses to exercise of highly endurance trained subjects after 3 different nights i.e. a baseline night, a partial sleep deprivation of 3 h in the middle of the night and a 0.25-mg triazolam-induced sleep. Sleep-waking chronobiology and endurance performance capacity were taken into account in the choice of the subjects. Seven subjects exercised on a cycle ergometer for a 10 min warm-up, then for 20 min at a steady exercise intensity (equal to the intensity corresponding to 75% of the predetermined maximal oxygen consumption) followed by an increased intensity until exhaustion. The night with 3 h sleep loss was accompanied by a greater number of periods of wakefulness (P less than 0.01) and fewer periods of stage 2 sleep (P less than 0.05) compared with the results recorded during the baseline night. Triazolam-induced sleep led to an increase in stage 2 sleep (P less than 0.05), a decrease in wakefulness (P less than 0.05) and in stage 3 sleep (P less than 0.05). After partial sleep deprivation, there were statistically significant increases in heart rate (P less than 0.05) and ventilation (P less than 0.05) at submaximal exercise compared with results obtained after the baseline night. Both variables were also significantly enhanced at maximal exercise, while the peak oxygen consumption (VO2) dropped (P less than 0.05) even though the maximal sustained exercise intensity was not different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748109 TI - Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids. AB - Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30 km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon. PMID- 1748110 TI - Physiological responses to prolonged treadmill walking with external loads. AB - Limited information is available regarding the physiological responses to prolonged load carriage. This study determined the energy cost of prolonged treadmill walking (fixed distance of 12 km) at speeds of 1.10 m.s-1, 1.35 m.s-1, and 1.60 m.s-1, unloaded (clothing mass 5.2 kg) and with external loads of 31.5 and 49.4 kg. Fifteen male subjects performed nine trials in random order over a 6 week period. Oxygen uptake (VO2) was determined at the end of the first 10 min and every 20 min thereafter. A 10-min rest period was allowed following each 50 min of walking. No changes occurred in VO2 over time in the unloaded condition at any speed. The 31.5 and 49.4 kg loads, however, produced significant increases (ranging from 10 to 18%) at the two fastest and at all three speeds, respectively, even at initial exercise intensities less than 30% VO2max. In addition, the 49.4 kg load elicited a significantly higher (P less than 0.05) VO2 than did the 31.5 kg load at all speeds. The measured values of metabolic cost were also compared to those predicted using the formula of Pandolf et al. In trials where VO2 increased significantly over time, predicted values underestimated the actual metabolic cost during the final minute by 10-16%. It is concluded that energy cost during prolonged load carriage is not constant but increases significantly over time even at low relative exercise intensities. It is further concluded that applying the prediction model which estimates energy expenditure from short-term load carriage efforts to prolonged load carriage can result in significant underestimations of the actual energy cost. PMID- 1748111 TI - The role of fitness on VO2 and VCO2 kinetics in response to proportional step increases in work rate. AB - The purpose of this study was to determine the effect of fitness and work level on the O2 uptake and CO2 output kinetics when the increase in work rate step is adjusted to the subject's maximum work capacity. Nine normal male subjects performed progressive incremental cycle ergometer exercise tests in 3-min steps to their maximum tolerance. The work rate step size was selected so that the symptom-limited maximum work rate would be reached in four steps at 12 min in all subjects. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated breath by breath. For the group, the time (mean, SEM) to reach 75% of the 3-min response (T0.75) for VO2 increased significantly (P less than 0.01) at progressively higher work rate steps, being 53.3 (5.5) s, 63.5 (4.6) s, 79.5 (5.0) s, and 94.5 (5.8) s, respectively. In contrast, T0.75 for VCO2 did not change significantly [74.9 (7.4) s, 75.6 (5.0) s, 85.1 (5.3) s, and 89.4 (6.3) s, respectively]. VCO2 kinetics were slower than VO2 kinetics at the low fractions of the subjects' work capacities but were the same or faster at the high fractions because of the slowing of VO2 kinetics. The first step showed the fastest rise in VO2. While VO2 kinetics slowed at each step, they were faster at each fraction of the work capacity in the fitter subjects. The step pattern in VO2 disappeared at high work rates for the less fit subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748112 TI - The critical role of iron in some clinical infections. AB - The role of iron in certain clinical infections is revealed. In normal persons the antibacterial and antifungal properties of blood and other tissue fluids cannot be maintained unless there are exceptionally low levels of available iron. This is controlled by the presence of the unsaturated iron-binding proteins, transferrin and lactoferrin. In several clinical conditions an abnormal availability of iron is responsible for fatal septicaemia. This is because the phagocytic system is overwhelmed by rapidly growing organisms when iron is freely available. PMID- 1748113 TI - The use of lysis-based procedures for blood cultures. PMID- 1748114 TI - Evaluation of the new improved BHI-lysis blood culture medium for the BCB Roche system. AB - The new BHI-lysis blood culture medium for the BCB system (BCB release, Hoffmann La Roche), which lyses blood cells, was compared with the BHI-S broth of the same BCB system and the Signal system (Oxoid). A total of 2394 sets consisting of three bottles were each inoculated with 7 ml of blood at the bedside. In the laboratory agar-coated paddles were attached to the BHI-lysis and the BHI-S bottles, and the Signal device was mounted onto the Oxoid bottle. All systems were incubated at 35 degrees C for seven days. Of the 309 (13%) positive sets, 73 (3%) were contaminated and in 242 (10%) sets a total of 250 pathogenic microorganisms were isolated. These could be grown significantly more often from the BHI-lysis bottle (n = 213) than from either the BHI-S (n = 189) or Signal bottle (n = 176). No significant differences in the time needed to achieve a positive result was noted between the BHI-lysis and BHI-S bottles, but comparison of the BHI-lysis and Signal bottles revealed that overall pathogens were detected earlier significantly more often with the BHI-lysis bottle. In view of the good performance of blood culture broths containing lysing agents, their wider use is warranted in future. PMID- 1748115 TI - Analysis of Escherichia coli isolates from subjects with travellers' diarrhoea using DNA probes and serotyping. AB - Escherichia coli isolated from faeces of 54 healthy volunteers who visited Tunisia for eight days were examined. These volunteers participated in a randomized double-blind placebo-controlled study to establish whether ciprofloxacin could prevent travellers' diarrhoea. Escherichia coli strains isolated before travel, during episodes of travellers' diarrhoea, immediately after return and five weeks after return were serotyped and tested for the presence of virulence genes indicating diarrheogenic properties by hybridization with a set of four non-radioactively labelled DNA probes. Subjects receiving ciprofloxacin prophylactically to prevent travellers' diarrhoea were asymptomatic and no Escherichia coli could be cultured shortly after return home. Sixty-four percent of subjects (18/28) who did not receive antibiotic prophylaxis suffered from travellers' diarrhoea. Hybridization tests detected 8 enterotoxigenic Escherichia coli strains producing heat stable toxin, 13 enterotoxigenic strains producing heat labile toxin and 10 strains which produced both heat labile and stable toxin. Of the 31 probe positive strains, 29 (94%) were cultured from 11 volunteers with travellers' diarrhoea. A bacterial cause was thus determined in 61% of the volunteers who experienced travellers' diarrhoea. PMID- 1748116 TI - Subtyping of Legionella pneumophila serogroup 1 isolates by small-fragment restriction endonuclease analysis. AB - Whole cell DNA of Legionella pneumophila isolates was examined by small-fragment restriction endonuclease analysis (SF-REA). Fourteen serogroup 1 isolates from tap water in one hospital collected before and after eradication measures had been taken were compared with control strains of serogroup 1 and other serogroups that were not epidemiologically linked. DNA was digested with EcoRI and electrophoresed on polyacrylamide gels. The gel patterns were made visible by silver staining and analysed by direct visual comparison. All 15 epidemiologically unrelated strains of Legionella pneumophila serogroup 1 and of other serogroups exhibited different restriction fragment patterns. The isolates from the hospital could be clearly subdivided into two groups by SF-REA, suggesting that the hot water supply of the hospital was contaminated with two different strains. SF-REA performed on Legionella pneumophila serogroup 1 DNA enabled further subtyping of these organisms and thus appears to be a useful technique for investigating their epidemiology. PMID- 1748117 TI - Nosocomial outbreak of acute gastroenteritis in a neonatal intensive care unit in Tunisia caused by multiply drug resistant Salmonella wien producing SHV-2 beta lactamase. AB - In a Tunisian hospital 27 babies, including 12 who were premature, in a single intensive care unit suffered acute gastroenteritis in the period from January to May 1988. The mean age at the onset of gastroenteritis was 8.4 days; nine babies died. Salmonella wien was isolated from stools (all babies) and blood (4 babies). It was also isolated from the stools of one nurse and from a mattress. Twelve of the babies had received cefotaxime, which was successfully replaced by oral colimycin. The outbreak was stopped by the implementation of infection control measures. All isolates of Salmonella wien were of the same biotype, and had the same antibiotic resistance pattern (third generation cephalosporins, monobactams, aminoglycosides, chloramphenicol, trimethoprim and sulphonamides) and plasmid DNA restriction pattern. The isolates were all susceptible to a combination of cefotaxime and clavulanic acid (a beta-lactamase inhibitor), which displayed synergy, suggesting the presence of a beta-lactamase (geometric mean MICs 11.24 micrograms/ml for cefotaxime alone and 0.24 micrograms/ml in combination with 0.1 micrograms/ml potassium clavulanate). All isolates produced TEM-1 and SHV-2 beta lactamase which was not transferable to Escherichia coli by conjugation. The presence of the SHV-2 enzyme in Salmonella wien may allow it to adapt to newer beta-lactams which is a cause for concern in this hospital. PMID- 1748118 TI - Comparison of the Bactec and lysis concentration methods for recovery of Brucella species from clinical specimens. AB - In a comparison of the Bactec system and the lysis concentration procedure in the isolation of Brucella species in 54 patients the recovery rate was similar (60% and 55%, respectively). However, the recovery time was significantly shorter with the lysis concentration method than with the Bactec system (3.5 days versus 14 days). The lysis concentration procedure for the culture of Brucella is simple, inexpensive and reliable, and produces results for the clinician relatively quickly. PMID- 1748119 TI - Quality control in antimicrobial disk susceptibility testing: a Belgian multicenter study. AB - A Belgian multicenter trial was conducted to evaluate problems encountered with quality control results of antimicrobial disk susceptibility testing and to compare the performance of BBL disks and Rosco tablets. Over a period of four weeks 18 laboratories daily tested three reference strains against eight antibiotics. A standardised method was used by all participants. For all results together 10.4% and 7.3% of the measurements with BBL disks and Rosco tablets, respectively, were outside the recommended range. Major problems were observed for some specific strain-antibiotic combinations. Standard deviations were similar for both systems; their precision was comparable. The results suggest that cooperation between manufacturers and some reference laboratories could be improved in order to establish optimal quality control limits. PMID- 1748120 TI - Comparison of different culture media for isolation of Chlamydia trachomatis by cell culture on HeLa cells. AB - The isolation yield and number of Chlamydia trachomatis inclusions was compared using DEAE-dextran pretreated HeLa cells cultured in four different media: Eagle's minimal essential medium (EMEM) with and without cycloheximide and Dulbecco's modification of EMEM (DMEM) with and without cycloheximide. Using DMEM without cycloheximide the number of inclusions was significantly higher than using EMEM without cycloheximide. In addition, the size of the inclusions was greatly enhanced. Use of DMEM or EMEM with cycloheximide yielded results comparable to those obtained with DMEM without cycloheximide. PMID- 1748121 TI - Detection of Chlamydia trachomatis by direct immunofluorescence improved by centrifugation of specimens. AB - During a study of women with laparoscopically investigated pelvic pain, genital tract specimens were examined for Chlamydia trachomatis using a direct fluorescent antibody (DFA) technique (MicroTrak, Syva) and culture. Some smears, particularly those from the upper genital tract, contained an inadequate number of cells when examined by the DFA technique and many cell monolayers were destroyed by the specimens. To obtain results for such samples, or to confirm the original DFA result, additional specimens which had been frozen at -70 degrees C or in liquid nitrogen were centrifuged at high speed and the resulting deposit examined by the DFA technique. By this means, 32 negative results were confirmed for specimens from 10 chlamydia-negative patients with pelvic inflammatory disease or with high chlamydial antibody titres, and 26 negative results were confirmed for 19 patients who were positive at other sites. In addition, three chlamydia-positive and six chlamydia-negative results were obtained for sites where the original smear for DFA testing had been inadequate (few epithelial cells) and six specimens that were negative originally were found to be positive. Thus, of 73 specimens that were either inadequate or negative by DFA testing originally, 9 (12%) were positive by DFA testing after centrifugation. PMID- 1748122 TI - Evaluation of a chemiluminometric immunoassay and a direct immunofluorescence test for detecting Chlamydia trachomatis in urogenital specimens. AB - A new chemiluminometric immunoassay (Magic Lite) and a direct immunofluorescence technique (MicroTrak) were compared with cell culture in the diagnosis of Chlamydia trachomatis infections. Both assays were evaluated using 260 genital specimens (89 men, 171 women), 26 of which were culture positive. The respective sensitivity of the chemiluminometric immunoassay and immunofluorescence technique was 88.5% and 84.6%, the specificity 97% and 99.6%, the positive predictive value 76.7% and 95.6%, and the negative predictive value 98.7% and 98.3%. Both methods could serve as an alternative to culture in the diagnosis of urogenital chlamydial infections. PMID- 1748123 TI - Comparison of the in vitro antifungal activity of free and liposome-encapsulated amphotericin B. AB - One hundred and four pathogenic yeast isolates (32 Candida albicans, 20 Candida tropicalis, 20 Candida parapsilosis and 32 Cryptococcus neoformans) and 21 mould isolates (13 Aspergillus spp. and eight Fusarium spp.), most of which were isolated from patients with cancer, were tested for susceptibility to free amphotericin B and a small unilamellar liposomal formulation of amphotericin B using a microbroth dilution method. Minimal fungicidal concentrations were also determined for Candida spp. and Cryptococcus neoformans. The minimal inhibitory concentrations of liposomal amphotericin B were comparable with those of the free drug; furthermore, the fungicidal activity of these two drugs did not differ significantly. PMID- 1748124 TI - In vitro activity of Ro 09-1428 compared to other cephalosporins. AB - The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms. Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040. Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates. The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins. For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM 1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P 99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH. PMID- 1748125 TI - In vitro activity of cefcanel versus other oral cephalosporins. AB - Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml. Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins. Clostridium spp. were inhibited by 0.25 micrograms/ml, 8- to 128 fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp. The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime. Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases. Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1. PMID- 1748126 TI - In vitro activity of the novel cephalosporin GR69153. AB - The in vitro activity of GR69153 was compared to that of ceftazidime, ceftriaxone, imipenem and gentamicin against a total of 702 recent clinical isolates. MICs were determined by a standard agar dilution procedure and two inocula (10(4) and 10(8) cfu) were used throughout. GR69153 inhibited 90% of isolates of Escherichia coli, Klebsiella pneumonia and Proteus mirabilis at less than or equal to 0.25 mg/l and 90% of isolates of Pseudomonas aeruginosa at less than or equal to 1 mg/l. Citrobacter freundii (MIC90 16 mg/l), Morganella morganii (MIC90 128 mg/l) and Enterobacter spp. (MIC90 greater than 128 mg/l) were considerably more resistant to GR69153. GR69153 was four-fold more active than ceftazidime against methicillin-sensitive Staphylococcus aureus but was inactive against methicillin-resistant Staphylococcus aureus, Enterococcus faecalis and Bacteroides fragilis group. PMID- 1748127 TI - Impact of dirithromycin on the normal oral and intestinal microflora. AB - Twenty healthy volunteers received 500 mg of dirithromycin orally once daily for seven days. The concentrations of dirithromycin in serum and saliva were low (less than or equal to 1.5 mg/l), while the faecal concentrations were high (greater than or equal to 12 mg/kg). The numbers of streptococci, Haemophilus and Neisseria increased in the aerobic oral microflora during dirithromycin treatment. In the aerobic intestinal microflora, the numbers of enterobacteria decreased significantly, while streptococci and staphylococci increased. New colonizing dirithromycin resistant enterobacteria were isolated during and after treatment. The anaerobic intestinal microflora was also affected; thus the numbers of gram-positive cocci, bifidobacteria, eubacteria and bacteroides decreased, while the numbers of clostridia and lactobacilli increased. Dirithromycin has an ecological impact on the oral and intestinal microflora. PMID- 1748128 TI - Actinobacillus hominis as a causative agent of septicemia in hepatic failure. PMID- 1748129 TI - Presumptive identification of Mycobacterium xenopi with the radiometric Bactec system. PMID- 1748130 TI - Federal early childhood special education policy: a model for the improvement of services for children with disabilities. AB - Services in early childhood special education for children with disabilities, birth through 5 years, and their families have expanded and improved substantially in the past 25 years. The federal government, through legislation, regulation, and a variety of incentives, has played an integral role in this progress. The authors review the evolution of federal education policy in early childhood and the accomplishments achieved, including the development of the Handicapped Children's Early Education Program, the Early Childhood Research Institutes, and Public Law 99-457, the Handicapped Infant and Toddler Program (Part H). This history can serve as a model for federal involvement in the improvement of services for other groups of individuals with special needs. PMID- 1748131 TI - Instruction in early childhood special education: "seeing through a glass darkly ... knowing in part". AB - This article discusses what is not known about instruction of preschoolers with disabilities. Knowledge gaps exist in four areas: the content of the curriculum, the procedures used to individualize instruction, the instructional procedures designed to ensure acquisition, and the strategies used to ensure skill use or generalization. Barriers to generating such knowledge include the fragmentation that results from specialization, the inadequacy of the data base, and the lack of training in instruction and research design and analysis. Solutions include training programs for early childhood special educators in the analysis, application, and design of research in instruction and curriculum, as well as the publication of multiple replications and refinements of instructional strategies. PMID- 1748132 TI - Mainstreaming during the early childhood years. AB - Issues surrounding the implementation of the integration imperative during infancy and early childhood present formidable challenges to education and community providers. Key among these issues is how professionals provide high quality services to young children with disabilities in mainstream environments. This article explores current issues related to integration and reexamines the concept of "best practices" as it applies to mainstreaming during the early childhood years. The author recommends an integrated set of indicators for high quality programs and describes an outcomes-based process for making administrative and pedagogical decisions. PMID- 1748133 TI - Clinical pharmacology in Europe. The WHO European Task Force on Clinical Pharmacology. PMID- 1748134 TI - Evaluation of three methods of symptom reporting in a clinical trial of felodipine. AB - 251 patients from 23 primary health care centres were recruited to a clinical trial in which either felodipine or placebo was added to baseline metoprolol treatment. Three methods of symptom reporting were used in 191 patients, namely two previously documented self-administered questionnaires and an adverse event monitoring system (spontaneous reports to treating physician). Higher frequencies of symptoms were seen with the questionnaires compared to spontaneous reporting. However, the overlap between the methods was moderate and they were found to complement one another. The questionnaires were completed twice during the study and the adverse event monitoring system was applied on five occasions. The rate of application had consequences for the ability of each method to detect transient, dose-related symptoms, e.g. headache and dizziness. Regardless of method, the possibility of detecting dose-related symptoms was enhanced when symptoms were measured not only during active treatment but also during a run-in or other baseline period, and both phases were considered in the analyses. PMID- 1748135 TI - Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension. AB - The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg on three separate occasions). Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks. A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP. PMID- 1748136 TI - Comparison of the cardiovascular effects of nifedipine and nicardipine in the presence of atenolol. AB - A placebo controlled double blind crossover study was performed in 12 healthy volunteers to compare the cardiovascular effects of single oral doses of nifedipine (5, 10 and 15 mg) and nicardipine (20 and 30 mg) in the presence of atenolol 100 mg. Haemodynamic measurements were made by transthoracic electrical bioimpedance cardiography (TEBC) 2 h following drug administration during passive tilting, graded bicycle exercise (30-150 W) and recovery from exercise. In the absence of calcium channel blockade, atenolol reduced mean blood pressure, heart rate, and cardiac index, and increased stroke volume, peripheral resistance, pre ejection period, and ventricular ejection time, particularly during and after exercise. In comparison with atenolol alone, addition of nifedipine or nicardipine reduced peripheral resistance but did not produce significant changes in stroke volume, cardiac output, dZ/dt [max], pre-ejection period (PEP). Ventricular ejection time (VET), PEP/VET, or Heather index at any point in the experiment. Similar reductions in peripheral resistance were produced by nifedipine 10 mg and nicardipine 20 and 30 mg. These apparently equivalent doses of nifedipine and nicardipine had similar effects on stroke volume, cardiac index, PEP/VET and Heather index. Thus the increases in ventricular performance previously demonstrated in association with nifedipine and nicardipine therapy were not observed in the presence of beta-adrenoceptor blockade. Under these conditions no important differences have been observed in the cardiovascular effects of these two calcium channel blockers. PMID- 1748137 TI - Combined effects of nicardipine and hypocapnic alkalosis on cerebral vasomotor activity and intracranial pressure in man. AB - The effect of hypocapnic alkalosis (HA) on nicardipine-induced cerebral vasodilatation was studied in 2 groups of patients undergoing stereotaxic brain biopsy under general anaesthesia. Arterial diameter (AD) was measured in 16 different locations on a carotid arteriogram (lateral view), and intracranial pressure (ICP) was recorded with an intraventricular catheter. At time T0, in normocapnia an arteriogram was performed in both groups. The first group (GI) was then studied in hypocapnia (T1) and following an injection of nicardipine (T2), while the second group (GII) was studied first after injection of nicardipine (T1) and then in hypocapnia (T2). Groups GI (n = 6; 44 y) and GII (n = 6; 46 y) were similar with regard to age, blood pressure, heart rate and PaO2 at all three phases of the study. HA caused a 9.5% decrease in AD (GI.T1) compared to baseline values, and a 15.2% decrease when preceded by injection of nicardipine (GII.T2). In the latter case the decrease was 3% in comparison with baseline. Nicardipine increased AD by 14.7% (GII.T1) and by 18.5% when preceded by HA (GI.T2), but the rise (7.3%) was not significant in comparison with the baselines value. The changes variations were similar whether the entire arterial trunk or only the supraclinoid region were studied. HA decreased ICP by 44% (GI.T1) and by 50% after nicardipine (GII.T2). Nicardipine did not cause an increase in ICP. Nicardipine and HA antagonise each others vasomotor effects, as previously shown in the baboon using nimodipine. PMID- 1748138 TI - Superior local tolerability of human versus salmon calcitonin preparations in young healthy volunteers. AB - Possible local and systemic adverse effects following administration of salmon (sCT) and human (hCT) calcitonin (CT) have been evaluated in a double-blind, within-subject, comparative trial in 30 young, healthy volunteers. Each subject received 0.25 and 0.5 mg hCT and 100 IU sCT s.c.. Adverse effects and hypocalcaemia were recorded 1, 3 and 6 h after each injection. Significantly fewer local adverse reactions were observed after hCT (20 or 33%) than after sCT (80%), possibly due to the different vehicles employed (mannitol solution and acetic acid). The most frequent systemic adverse effects were gastrointestinal (nausea, vomiting), which occurred in 80% after 1 h, independently of the CT- preparation used. Hypocalcaemic changes were generally small and lasted longer after sCT. It is concluded that the hCT preparations were better tolerated locally than sCT in young, healthy volunteers, and that there were no differences in the systemic side effects or hypocalcaemic activity. PMID- 1748139 TI - Effect of pentoxifylline on liver plasma flow in normal man. AB - In ten healthy, male subjects the acute effect of pentoxifylline (a methylxanthine derivative) on liver plasma flow was investigated by the extrarenal sorbitol clearance method and on cardiac output by impedance cardiography. On the placebo day liver plasma flow decreased within 4 h from 769 to 683 ml.min-1 (P less than 0.05) and on the pentoxifylline day (300 mg i.v.) it increased from 764 to 801 ml.min-1 (NS). At the end of the experiment the difference between the groups was also significant (P less than 0.05). There was no significant change in cardiac output, blood pressure or heart rate and individual changes in those values were not correlated with liver plasma flow. There was no correlation either between the plasma concentrations of pentoxifylline or its metabolites and the changes in liver plasma flow. It is concluded that, relative to the spontaneous decrease in liver plasma flow at rest on the placebo day, pentoxifylline increased splanchnic perfusion independent of any change in cardiac output. PMID- 1748140 TI - Effect of loperamide on jejunal electrolyte and water transport, prostaglandin E2 induced secretion and intestinal transit time in man. AB - Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2-8 mg.l-1). The volunteers were pretreated with 1 mg.l-1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg.l-1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT). Loperamide 2 mg.l-1 converted the minor secretion after perfusion with the standard solution (water -145 ml.min-1, Na -0.09 and Cl -0.04 mmol.min 1) to absorption (water 0.93 ml.min-1, Na 0.23, Cl 0.25 mmol.min-1) within 15 min. Higher doses of loperamide did not increase absorption. The addition of PgE2 induced net secretion of water (-4.48 ml.min-1) and electrolytes (Na -0.57, Cl 0.51 mmol.min-1). Loperamide 4 mg.l-1 significantly diminished the PgE2-induced net secretion by approximately 50%. Loperamide dose dependently increased the MTT from 6 (2 mg.l-1) to 13.3 min (8 mg.l-1). MTT was still delayed 60 min after a wash out period (10.5 min). It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses. PMID- 1748141 TI - Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers. AB - Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml.min-1, while plasma antithrombin and thrombin generation inhibiting (TG1) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng.ml-1.h, and a significant reduction in the average serum digoxin concentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined. PMID- 1748142 TI - Pharmacokinetics of tiaprofenic acid in children after a single oral dose. AB - Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg.kg-1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age: tmax = 2.12 h, Cmax = 8.78 mg.l-1, AUC(0- --8 h) 33.9 mg.h.l-1, AUC = 39.3 mg.h.l-1, t1/2 = 2.35 h, Vt = 0.319 l.kg-1, CL = 0.094 l.h-1.kg-1. Renal clearance was 14 ml.h-1.kg-1.33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg.kg-1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3-11 year old children from that in adults. PMID- 1748143 TI - Ambulatory blood pressure monitoring in elderly hypertensives treated with the new calcium antagonist, nilvadipine. AB - A newly developed calcium antagonist, nilvadipine, was administered to 7 hypertensive patients aged 75.6 y. Nilvadipine 4 mg b.d. decreased the average 24 h blood pressure significantly from 169/89 mmHg to 152/81 mmHg after 7 to 14 days without any change in the pulse rate. The circadian patterns of blood pressure and pulse rate were not affected by nilvadipine. Although the present study was a preliminary one done over a short period in a small number of patients, the results suggest that nilvadipine exerts an antihypertensive effect without altering the circadian pattern or the variability of blood pressure in elderly hypertensive patients. PMID- 1748144 TI - Plasma level monitoring of mitotane (o,p'-DDD) and its metabolite (o,p'-DDE) during long-term treatment of Cushing's disease with low doses. AB - Mitotane (o,p'-DDD) can be used for the treatment of various adrenocortical diseases such as Cushing's syndrome, but the usual doses of 6-8 g per day are often associated with severe adverse effects. This paper reports the results of much lower doses of o,p'-DDD (0.5-2 g per day) in two patients with Cushing's disease over periods of 8 and 5 years, respectively, under concomitant monitoring of the plasma levels of the parent drug and its major metabolite, o,p'-DDE. It became apparent that o,p'-DDD and o,p'-DDE have a strong tendency to accumulate in the body due to their high lipophilicity. As a consequence, changes in dose regimens had long lag times before they were reflected in plasma levels and once an increase or decrease had started one had to be careful not to cause overshoot. Steady state plasma levels of o,p'-DDD between 5-10 micrograms/ml appeared sufficient to induce and to maintain remission of the disease, which was accompanied with normal cortisol levels in plasma and urine. DDD-levels below 5 micrograms/ml for several weeks may lead to relapses, whereas DDD-levels over 10 micrograms/ml gave rise to side effects. On the other hand, o,p'-DDE seemed inactive at levels up to 4 micrograms/ml in plasma. PMID- 1748145 TI - Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles. AB - Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year. The drugs had an equivalent effect on glycaemic control, but, in contrast to glibenclamide, metformin reduced body weight. Neither drug affected triglycerides, total- and LDL-cholesterol or C peptide. Metformin caused a slight elevation of HDL-cholesterol (P less than 0.05). No serious adverse effects were observed. The results show that oral hypoglycaemic agents are not associated with undesirable effects on lipids and lipoproteins. PMID- 1748146 TI - Identification of thymocyte precursors in murine fetal liver. AB - We have isolated thymic stem cells from murine fetal liver using a combination of approaches including discontinuous albumin density gradient separation and anti heat-stable antigen (HSA) antibody plus complement-mediated lysis. A population of early precursors has been identified which comprises approximately 1% of fetal liver, and which has the capacity to reconstitute alymphoid lobes and give rise to the four thymic subpopulations defined by expression of the T cell differentiation antigens CD4 and CD8. These early precursors express CD44 (Pgp 1), however, they are negative for expression of Thy-1, CD4, CD8, CD3, membrane immunoglobulin and HSA cell surface molecules. PMID- 1748147 TI - Limiting dilution analysis of proliferative T cell responses to mycobacterial 65 kDa heat-shock protein fails to show significant frequency differences between synovial fluid and peripheral blood of patients with rheumatoid arthritis. AB - Recent evidence has pointed to the mycobacterial 65-kDa heat-shock protein (hsp 65) as an antigen that may be important in the pathogenesis of rheumatoid arthritis (RA). Using limiting dilution analysis the frequency of purified protein derivative of tuberculin (PPD) and hsp 65-responsive T cells was measured in paired peripheral blood and synovial fluid samples of patients with RA. There was no increase in the anti-PPD or anti-hsp 65 frequency in synovial fluid compared with peripheral blood. In addition, no difference was found between peripheral blood of RA patients and healthy controls. These results do not support the idea of an important pathogenic role of T cells responding to hsp 65, or a cross-reacting antigen, in RA. PMID- 1748148 TI - Sites of specific B cell activation in primary and secondary responses to T cell dependent and T cell-independent antigens. AB - Techniques which identify hapten-specific B cells in tissues have been used to determine the sites of B cell activation in rat spleens in response to T cell dependent (TD) antigens and T cell-independent type-1 (TI-1) antigens. Surface associated hapten binding by specific memory B cells and B blasts was distinguished from the strong cytoplasmic hapten binding by specific plasma cells and plasmablasts. Blast cells in S phase were identified in tissue sections by staining cells which had been pulse labeled in vivo with 5-bromo-2'-deoxyuridine. Hapten-specific B blast cells are found in three sites: (a) around interdigitating cells in the T cell-rich zones; (b) in the follicular dendritic cell network and (c) in association with macrophages in the red pulp. Hapten binding memory B cells, which are not in cell cycle, accumulate in the marginal zones and to a lesser extent the follicular mantles in response to TD and TI-1 antigens. The hapten-specific blast response in T zones is confined to the first few days after antigen is given and is low for primary responses to TD antigens, but massive on secondary challenge, when marginal zone memory B cells migrate to the T zones. Both the primary and secondary T zone responses to TI-1 antigens are impressive and in these responses hapten-specific B blasts are also found in the splenic red pulp. The follicular response to TD antigens starts with a small number of B blasts (fewer than five) entering each follicle. These increase in number exponentially so that by the 4th day after immunization they fill the follicle. The oligoclonality of the response is shown in simultaneous responses to two haptens where 6%-31% of the follicles on day 3 after immunization contain blasts specific for only one of the two haptens. During the 4th day classical zonal pattern of germinal centers develops. The surface immunoglobulin-positive B blasts are lost from the follicle center, while one pole of the follicular dendritic cell network fills with surface immunoglobulin-negative centroblasts. Centroblasts do not increase in numbers but divide to give rise to centrocytes, which re-express sIg and migrate into the follicular dendritic cell network. Cell kinetic studies indicate that the centrocyte population is renewed from centroblasts every 7 h. Centrocytes either leave the germinal center within this time or die in situ.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1748149 TI - Cross-linking of surface IgM activates NF-kappa B in B lymphocyte. AB - In B lymphocytes, cross-linking of surface IgM activates changes in both the cell cycle and differentiation. In normal B cells and B cell tumors, many stimuli induce the activation of NF-kappa B and its translocation from the cytoplasm to the nucleus. In this study we sought to determine if cross-linking of surface IgM led to the activation of NF-kappa B. Our results show that activation of B cells by cross-linking anti-IgM antibodies activated NF-kappa B in the murine B lymphoid cell lines 70Z/3 and M12, and in the dense fraction of splenic cells. The activation of NF-kappa B required optimal doses of anti-IgM antibodies and took 5 to 10 min to reach maximal levels. Cross-linking of IgM has also been shown to activate protein kinases including protein kinase C (PKC). To test whether PKC activation was required for NF-kappa B translocation, we treated 70Z/3 cells for 18 h with phorbol 12-myristate 13-acetate, a procedure which depletes these cells of functional PKC. This treatment did not abrogate the nuclear translocation of NF-kappa B following anti-IgM cross-linking. These results indicate that the nuclear translocation of NF-kappa B is rapidly induced by surface IgM cross-linking and that this activation appears to use a pathway which does not require PKC. PMID- 1748150 TI - Immunoglobulin heavy chain cDNA from the teleost Atlantic cod (Gadus morhua L.): nucleotide sequences of secretory and membrane form show an unusual splicing pattern. AB - Rabbit antibodies to Atlantic cod (Gadus morhua L.) immunoglobulin were affinity purified and used to screen cDNA libraries from spleen and head kidney mRNA. cDNA clones for both the secretory and membrane-bound heavy (H) chain were isolated, the nucleotide and deduced amino acid sequences of which are reported here. Comparisons of the cod secretory H chain amino acid sequence show 24%, 27%, 30% identity to the mu chain of Mus, Xenopus and Ictalurus, respectively. The highest degree of identity was observed in the CH4 domain. The cDNA encoding the transmembrane form shows a novel splicing pattern where the TM1 exon is spliced directly onto the CH3 domain and not to the CH4 domain as in other animal groups. Southern blot analyses with VH and C probes on genomic DNA from cod erythrocytes indicate that there is a unique C gene but several V genes in the cod immunoglobulin H chain locus. PMID- 1748151 TI - Polarized expression of major histocompatibility complex class I molecules in human endometrial and endocervical epithelial cells. AB - The localization of major histocompatibility complex (MHC) class I molecules in human endometrial and endocervical epithelial cells was studied with an immunogold technique on ultrathin cryosections. At the cell surface, MHC class I molecules are delivered solely to the basolateral plasma membrane in human epithelia. Therefore, only the basolateral domain of epithelial cells is capable of presenting antigen to MHC class I-restricted cytotoxic T cells. PMID- 1748152 TI - Prolonged survival of skin grafts following treatment with an antibody to a putative cell triggering molecule, QCA-1. AB - The QCA-1 molecule (quiescent cell antigen-1) appears to be involved in the differentiation events undergone by T cell following occupancy of the antigen receptor. Here we show that modulation of the QCA-1 antigen from the surface of the cell normally follows activation, and that treatment of animals with the antibodies against the QCA-1 molecule inhibits the normal response to an allograft without appearing to alter the number of peripheral T cells or the expression by these cells of the alpha/beta T cell antigen receptor. PMID- 1748153 TI - Characterization of somatodendritic neuronal nicotinic receptors located on the myenteric plexus. AB - The effects of nicotine and dimethylphenylpiperazinium (DMPP) on resting and stimulation-evoked release of [3H]-acetylcholine ([3H]ACh) from cholinergic interneurons and neuro-effector neurons of the ileal longitudinal muscle and the responses of the smooth muscle to nicotinic agonists were studied. (-)-Nicotine was 15 times more effective than (+)-nicotine in releasing ACh. Since tetrodotoxin (1 microM) completely antagonized the effect of nicotinic agonists, the site of action of the nicotinic agonists studied was on the somatodendritic nicotinic receptors. The electrical field stimulation-evoked release was not affected by nicotinic agonists and antagonists, indicating that the axon terminals of cholinergic interneurons are not equipped with nicotinic receptors. This preparation proved to be useful to study the effect of nicotinic agonists on somatodendritic receptors, to determine the affinity constants of nicotinic antagonists, and to characterize these receptors. The rank order of antagonists was d-tubocurarine = mecamylamine greater than pipecuronium greater than pancuronium greater than vecuronium greater than hexamethonium; the apparent affinity constants (KD) were 1.15, 1.55, 3.06, 3.98, 13.59 and 32.88 microM, respectively. alpha-Bungarotoxin had no antagonistic activity at all. This finding indicates that nicotine and the endogenous ligand ACh act via a postsynaptic, somatodendritic nicotinic receptor that is pharmacologically similar to those located on the axon terminals of sympathetic neurons or in ganglions, but is dissimilar to those located at the postsynaptic site of the neuromuscular junction. PMID- 1748154 TI - Inhibition of the first ovulation and ovarian prostaglandin F2 alpha metabolism by danazol in rats. AB - The present study was conducted to investigate the mode of action of danazol by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PG) F2 alpha metabolism in pregnant mare serum gonadotropin (PMSG) primed immature female rats. When danazol (750 mg/kg) was given p.o. once a day for 5 days (day 24-28), the occurrence of the first ovulation, the increase in capacity to form 13,14-dihydro-PGF2 alpha and PGF2 alpha levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazol also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazol on ovulation and ovarian PGF2 alpha metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland. PMID- 1748155 TI - Nonpeptide angiotensin II receptor antagonists. Studies with DuP 753 and EXP3174 in dogs. AB - DuP 753 (or EXP3174) and PD123177 are nonpeptide angiotensin (AII)-specific ligands, which show high affinities for two AII receptor subtypes, i.e. AT1 and AT2 sites, respectively. In furosemide-treated conscious dogs with high renin, DuP 753 and EXP3714, but not PD123177, were as effective as captopril in lowering blood pressure. Both DuP 753 and EXP3174 exhibited selective vascular antagonism of AII. In conscious dogs with normal renin, DuP 753, but not captopril or EXP3174, caused a dose-dependent but transient decrease in blood pressure. In anesthetized dogs, DuP 753 and captopril caused similar renal vasodilatation and natriuresis. The renal hemodynamic effects of DuP 753 and captopril were more pronounced in dogs with sodium depletion. These results suggest that the AT1 receptor mediates the pressor and renal effects of AII in dogs. The acute transient hypotensive effect of DuP 753 in normal-renin conscious dogs is probably unrelated to AII antagonism. PMID- 1748156 TI - Arginine8-vasopressin potentiates the motor incoordinating effects of pentobarbital. AB - Arginine8-vasopressin (AVP, 10 micrograms), injected s.c., potentiated the motor impairing effects of pentobarbital (10-20 mg/kg) injected i.p. in rats 1 h after AVP. Motor incoordination was assessed on the moving belt task. However, AVP (0.1 100 nM) failed to enhance pentobarbital potentiation of GABA-mediated 36Cl- uptake in rat cerebral cortical or cerebellar microsacs. There was also no effect of a 10 micrograms s.c. injection of AVP 1 h before killing, on pentobarbital potentiation of GABA-mediated chloride flux in either cerebral cortical or cerebellar microsacs. PMID- 1748157 TI - Effects of propentofylline on adenosine A1 and A2 receptors and nitrobenzylthioinosine-sensitive nucleoside transporters: quantitative autoradiographic analysis. AB - Previous studies have demonstrated that the xanthine compound, propentofylline, has beneficial effects in models of cerebral ischemia and can enhance some and exhibit other effects of adenosine. We investigated the in vitro effects of propentofylline and its hydroxy metabolite, A72,0287, on the binding of [3H]cyclohexyladenosine ([3H]CHA), [3H]2-[p-(2-carbonyl-ethyl)-phenylethyl-amino] 5'-N- ethylcarboxamido adenosine ([3H]CGS 21680) and [3H]nitrobenzylthioinosine ([3H]NBMPR) to adenosine A1 and A2 receptors and NBMPR-sensitive nucleoside transporters, respectively, in 10-microns coronal rat brain sections. Both xanthines had micromolar affinity for each of these sites with approximately 10 fold lower affinity for A2 receptors than for A1 receptors and [3H]NBMPR binding sites. Saturation analysis of [3H]CHA or [3H]CGS 21680 binding in the presence of increasing concentrations of propentofylline produced significant increases in KD values without affecting Bmax values; thus propentofylline is a competitive inhibitor at A1 and A2 receptors. The effects on A2 receptors apparently require higher concentrations (Ki approximately 200 microM) than the effects on A1 receptors (Ki approximately 20 microM). Propentofylline was also found to be a competitive inhibitor of [3H]NBMPR binding. Therefore we conclude that propentofylline interacts with adenosine-responsive systems to increase interstitial adenosine concentrations and to selectively inhibit A1 receptors. PMID- 1748158 TI - Staurosporine, a protein kinase inhibitor, attenuates intracellular Ca(2+) dependent contractions of strips of rabbit aorta. AB - The protein kinase inhibitor staurosporine was found to be a potent relaxant of rabbit aortic strips contracted by various agonists. This relaxing effect was slow, long-lasting and in a non-competitive fashion against various agonists. The effect of staurosporine on the KCl-induced contraction was not altered by atropine, propranolol, theophylline or indomethacin. Staurosporine (5-200 nM) inhibited the contractile responses to prostaglandin F2 alpha (3 microM), endothelin (0.1 microM), phenylephrine (3 microM) and KCl (30 mM), with ED50 values of 10.8 +/- 0.6, 24.6 +/- 8.7, 48.8 +/- 7.0, 54.0 +/- 12.7 nM, respectively. Even in Ca(2+)-free physiological salt solution, staurosporine potently antagonized the contractile responses elicited by 10 microM prostaglandin F2 alpha and 0.1 microM endothelin; in fact it was more effective than it was in normal Ca2+ solution: ED50 of 11.3 +/- 3.8 vs. 21.0 +/- 4.4 nM (P less than 0.02), and of 10.6 +/- 3.6 vs. 24.6 +/- 4.3 nM (P less than 0.01), respectively. Thus, staurosporine has an equipotent inhibitory action on intracellular and extracellular calcium-dependent contractions of aortic tissues. PMID- 1748159 TI - Buspirone inhibits corticotropin-releasing factor and stress-induced cecal motor response in rats by acting through 5-HT1A receptors. AB - The effect of buspirone on corticotropin-releasing factor (CRF) and stress stimulated cecal motility and its antagonism by 5-HT1A (spiroxatrine) and sigma (BMY 14802) antagonists were evaluated by electromyography in rats equipped with chronically implanted electrodes on the cecum and a small catheter into the right lateral ventricle of the brain. Exposure to mental stress, consisting of a fear conditioned response, increased during 30 min the frequency of cecal spike bursts significantly (P less than 0.01). The frequency of cecal spike bursts was also increased following intracerebroventricular injection of CRF (500 ng/kg). Buspirone (1 mg/kg s.c.) abolished the stimulatory effects of mental stress and CRF on cecal motility. Whereas spiroxatrine (0.5 mg/kg s.c.) blocked the effect of buspirone on the colonic hypermotility induced by i.c.v. injection of CRF, BMY 14802 at a similar dose (0.5 mg/kg s.c.) was unable to block the action of buspirone. It is concluded that s.c. administration of buspirone suppresses the stress-induced cecal motor response through 5-HT1A receptors, probably by inhibiting the central or peripheral pathways involved in CRF mediation of these effects. PMID- 1748160 TI - Changes in motor activity and forebrain [propionyl-3H]propionylated-CCK-8 binding in mice after repeated administration of drugs affecting cholecystokinin receptors. AB - The effects of acute or repeated treatment of male albino BKW mice with caerulein, a cholecystokinin octapeptide (CCK-8) agonist, and with devazepide (MK 329) and L-365,260, antagonists at CCKA ('peripheral') and CCKB ('central') receptors respectively, on motor activity and [propionyl-3H]propionylated-CCK-8 ([3H]pCCK-8) binding were studied. Acute treatment with a large dose of caerulein (100 micrograms/kg s.c.) suppressed motor activity (line crossings and rearings) whereas devazepide (2 mg/kg i.p.) had the opposite action. L-365,260 (2 mg/kg i.p.) increased only the number of rearings. Tolerance developed to the locomotor effects of caerulein and devazepide when these same doses were administered once daily (caerulein) or twice daily (devazepide) for 10 days. Twice daily administration of L-365,260 (2 mg/kg) for 10 days did not significantly alter the locomotor activity of mice. The sedative effect of caerulein (20 micrograms/kg s.c.) was markedly reduced in mice receiving repeated injections of either a larger amount of caerulein (100 micrograms/kg) or devazepide but not after L 365,260. The stimulant effect of (+)-amphetamine (2 mg/kg s.c.) on motor activity was increased by subchronic administration of either devazepide or caerulein, but not by L-365,260. All three compounds (caerulein, devazepide and L-365,260) increased the number of [( 3H]pCCK-8 binding sites in mouse forebrain but the increase was only significant after L-365,260. The effects of long-term treatment with caerulein are probably related to the stimulation of CCKA receptors, whereas the paradoxically similar action of devazepide may be linked to the blockade of both subtypes of the CCK-8 receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748161 TI - Colonization of R plasmid-bearing Escherichia coli strains in the mouse alimentary tract. AB - In order to examine the ability of R plasmid-bearing Escherichia coli strains to colonize in the mouse alimentary tract, an R plasmid-positive (R(+)) E. coli strain and its R plasmid-negative (R(-)) counterpart were together inoculated into the streptomycin-treated mouse alimentary tract, and the numbers of fecal E. coli strains were enumerated. The numbers of R(+) strains were always at the level similar to or lower than those of their counterparts and rapidly decreased in the fecal population. However, when R plasmids, which were originated from a cryptic plasmid of the host E. coli strain, were utilized, an R(+) strain dominated over its R(-) counterpart during the experimental period. These experimental results indicated that the relationship between the host strain and R plasmids affected the ability of the host strain to colonize in the alimentary tract. PMID- 1748162 TI - [An injection-corrosion study on the angioarchitecture of rat skin]. AB - The angioarchitecture of the skin in the SD strain rat was investigated by scanning electron microscopy using resin cast. The neck part of rat skin was composed of 3 layers of vascular networks: the first layer (superficial layer), the second layer (middle layer), and the third layer (deep layer). Two types of capillary architectures were present around the hair follicle: small architectures composed of random network and large architectures composed of 3 parts distinguished by the construction of network. The large architecture, the capillary of hair papilla and the capillary network of sebaceous gland was thought to compose one circulation unit. The afferent vessels into such units branched from Kandelaberarterie-Petersen occurring from the 3rd layer, ascended to the 2nd layer, then descended to the bottom of the network and composed the capillary architecture. There were 2 types of efferent vessels from such circulation unit. They occurred from superficial and deep part, respectively, of the vascular architecture around the hair follicle and descended straight to the 3rd layer. The presence of straight vessels between the 2 nd and 3 rd layer, and the simple arrangement of vascular layers were thought to be characteristic of the angioarchitecture of the rat skin. PMID- 1748163 TI - Effects of methamphetamine on copulatory behavior in male rats. AB - Many papers have reported the effect of amphetamine and its close relative, methamphetamine on sexual activity in humans. The effect of these drugs on animal sexual behavior is unknown. The present study was done to determine whether methamphetamine modifies the copulatory behavior of male rats. Sexually experienced rats of the Wistar-Imamichi strain, 10 weeks of age, were singly injected intraperitoneally with methamphetamine hydrochloride at doses of 0, 1, 2 or 4 mg/kg body weight. Tests were initiated at 19: 30 in the dark period. Observations were conducted for 90 min. At dosages of 1 or 2 mg/kg there were no changes in copulatory behavior ascribed to the administration of methamphetamine. At 4 mg/kg the frequencies of mounting, intromission and ejaculation were greatly decreased but the spontaneous motor activity and stereotypic behavior increased in all males. In a further experiment, males were given methamphetamine by intraperitoneal injection once a week for 8 weeks. The copulatory behavior was tested 5 times at two weeks intervals. In the 4th testing, the percentage showing ejaculation decreased. In the 5th testing, there was no ejaculation and the incidence of intromission decreased. No stereotypic behavior was displayed in any of the males during the testing. From these results, it was concluded that methamphetamine inhibits the intromitting and ejaculating behavior in male rats. PMID- 1748164 TI - Mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats in studies of chronic toxicity and carcinogenicity. AB - In vivo historical control data, including mortality, body weight, food and water consumption, and clinical signs in F344/DuCrj rats were obtained from 11 long term toxicity and carcinogenicity studies conducted at the Biosafety Research Center, Foods, Drugs and Pesticides, (An-Pyo Center) during the last five years. Survival at 109 weeks of age was 80.2% (min: 74%, max: 90%) in males and 80.5% (min: 72%, max: 92%) in females. The maximum mean body weights of males and females were 443.3 +/- 15.8 g (mean +/- S. D.) and 295.7 +/- 13.3 g respectively. Male rats attained their maximum body weight at 82.6 +/- 5.3 weeks of age, the females at 103.5 +/- 2.5 weeks of age. Clinical symptoms increased with age, particularly after 84 weeks of age, and included: wasting, piloerection, palpable subcutaneous and abdominal masses, and decreased spontaneous movement. Lowered body temperature and auricular pallor occurred commonly in moribund animals. The nature and grade of toxicity in the treated animals were generally disclosed by comparing with the behavior and signs in the control animals. The use of in house, historical control data can be useful in subsequent evaluations of chronic toxicity and carcinogenicity studies. PMID- 1748165 TI - [Effects of captopril on acute phase in two-kidney Goldblatt hypertensive rats and spontaneously hypertensive rats]. AB - Effects of continuous oral administration of captopril were investigated on acute phase in two-kidney Goldblatt hypertensive (2 KGH) rats and spontaneously hypertensive rats (SHR). Systolic blood pressure gradually rose throughout the experimental period of 7, 14, 21 and 28 days in both 2 KGH rats and SHR. These gradual increases of systolic blood pressure were reduced by administration of captopril in both rats. Plasma renin activity were markedly increased throughout the experimental period in both rats treated with captopril, and were modestly increased in 2 KGH rats. In contrast, those changes in plasma renin activity were not obvious in SHR. In 2 KGH rats, juxtaglomerular index (JGI) and juxtaglomerular cell count (JGCC) of the clipped kidneys increased whereas JGI of the opposite kidneys decreased. In contrast, those changes in JGI and JGCC were not obvius in SHR. On the other hand, JGI and JGCC of the clipped kidneys increased in 2 KGH rats treated with captopril and those of the both kidneys increased in SHR treated with captopril. These results suggested that juxtaglomerular cells were related to the development of hypertension in 2 KGH rats, but were not clear in SHR. And these results were found that captopril showed antihypertensive effects, in spite of rises in JGI and JGCC of both 2 KGH rats and SHR. PMID- 1748166 TI - [Cryopreservation of mouse spermatozoa]. AB - The spermatozoa of cauda epididymis of mature mice were suspended in 3% skim milk in distilled water supplemented with 12, 15, 18 or 21% (W/V) raffinose. The suspension of spermatozoa were frozen in liquid nitrogen gas for 10 min, then stored in liquid nitrogen (-196 degrees C). The frozen suspensions of spermatozoa were thawed by rapid warming in water bath at room temperature. For removing the cryopreservative solution, a pair of syringes connected with a three stop cock and a filter unit (pore size 0.45 mu) were used. Highest sperm motility was obtained after 1 hr of thawing from the cryopreservative solution containing 18% raffinose and 3% skim milk. These cryopreserved spermatozoa were used for fertilization in vitro. The proportion of pronuclear oocytes was 35.9% (74/206) 6 hr after insemination, and the proportion of 2-cell embryos was 33.6% (42/125) 28 hr after insemination. All 2-cell embryos were transferred to the oviducts of pseudopregnant recipients and 45.2% (19/42) developed to normal young. PMID- 1748167 TI - Effect of the energy density of non-purified diets on reproduction, obesity, alopecia and aging in mice. AB - Four diets with graded levels of energy at 24% crude protein were fed to C57BL/6J mice for approximately 3 years to develop pelleted non-purified diets. The nitrogen-corrected metabolizable energy (MEn) of the diets ranged from 2.86 to 3.73 kcal per g of dry matter (DM). Fifteen males and 30 females were assigned to each diet. The mice were housed together for 1 week at 7 week intervals, experiencing 5 matings. After the reproduction stage, they were allowed to complete their life span. Moribund mice after 60 weeks of age were subjected to histopathological examination. The highest energy diet showed the following results in comparison with the lowest energy diet: (1) weaning weight of pups increased by 31.6%; (2) males showed slight obesity even during the reproduction stage, but females did not; (3) both sexes developed remarkable obesity after 50 weeks of age with 41.2% (males) and 49.6% (females) increasing in maximum body weight; (4) although daily feed intake decreased by approximately 18%, the MEn was slightly over consumed; (5) females showed higher incidence of alopecia with age; (6) the survival rate after 50 weeks of age decreased earlier and life span was shortened; (7) histopathological changes associated with aging developed earlier. On the other hand, the early death rate of dams at parturition increased with a decrease in dietary energy. It was concluded that at least 2 types of diets are needed throughout the life span of C57BL/6J mice; a high energy diet with an MEn value of 3.73 kcal/g DM for maximum reproduction and a low energy diet with an MEn value of 2.86 kcal/g DM for the long term stage after reproduction to retard obesity and aging most effectively. PMID- 1748168 TI - [Pituitary and plasma levels of growth hormone (GH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) in hereditary dwarf rats (rdw/rdw)]. AB - Koto et al found a new hereditary dwarf mutation from breeding colony of Wistar Imamichi rat and named 'rdw'. To characterize endocrinological functions in rdw rats, pituitary and plasma levels of pituitary hormones including growth hormone (GH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were compared between rdw and normal rats. The hormone levels were estimated with radioimmunoassay (RIA). It was found that pituitary and plasma levels of GH of rdw were drastically decreased and those of FSH and LH were inclined to decrease but not remarkable as compared with normal. Rats of rdw were, therefore, considered to be useful as a model animal for endocrinological defects. PMID- 1748169 TI - Effects of germfree status and food restriction on longevity and growth of mice. AB - An investigation was undertaken to study the effects of germfree (GF) status and mild food restriction on life span in GF and specific pathogen-free (SPF) male ICR mice either full-fed (ad libitum) or on a restricted diet of 4.5 grams per day (equivalent to approximately 80% of full-fed intake) from five-week-old. The mean life span of the full-fed SPF and GF mice was 75.9 and 88.9 weeks respectively, while the mean life span of the food-restricted SPF and GF mice was 117.5 and 109.6 weeks, respectively. Mice in both GF and SPF food-restricted groups were characterized by lower body weight and increased survival. These findings suggest that the cessation of growth may be importantly and perhaps causally related to longevity. The GF mice survived longer than the SPF mice, but the combination of GF status with food restriction did not seem to extend life span more than food restriction alone. PMID- 1748170 TI - Stumpy limb--an embryonic lethal mutation in Japanese quail (Coturnix coturnix japonica). AB - An embryonic lethal mutant was found in Japanese quail and named "stumpy limb (SL)". All SL embryos died at pre-hatching stages, showing brachycephaly, a thickened neck, short upper and lower beaks, and short and thick extremities, while their body length was similar to that of the normal embryos. Observations on the skeleton revealed a globular skull, unusual curvature of the Processus palatinus maxillaris of the upper beak, and shortening and thickening of the appendicular bones. Some embryos showed a bending of the humerus, femur and/or tibiotarsus. Abnormality was more conspicuous in the leg bones than in the wing bones. No conspicuous differences were observed in the vertebrae between the SL and normal embryos. A genetic analysis suggested that the mutation is controlled by an autosomal recessive gene, for which the gene symbol sl was proposed. PMID- 1748171 TI - Comparative studies of some functional and morphological parameters in the livers of germfree, conventional and ex-germfree mice. AB - Some parameters of hepatic function and morphology were studied to compare germfree (GF) and conventional (CV) BALB/c mice. The levels of lipid peroxide (LPO) and aniline-hydroxylase (AH) activity in the livers and the serum total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were significantly lower in GF than in CV 8-week-old mice. There were no significant differences in the histology and lectin-histochemistry of the livers in the GF and CV mice. On the other hand, in ex-GF mice which were induced by housing 4-week-old GF mice together with age-matched CV mice, the levels of LPO and AH activity in the liver and the serum TC, TG and PL contents increased rapidly within the first week and then approached values almost identical to those in CV mice 4 weeks later (i.e. at 8 weeks of age). The histologic picture of the liver was similar among the GF, CV and ex-GF mice. PMID- 1748172 TI - [Marked difference in sensitivity to gamma-ray-induced cataract between BALB/c and CBA-C3H strain mice]. AB - Nineteen BALB/c, 14CBA/KI, 12C3H/HeJ and 15 (CBA/Kl x C3H/HeJ) F1 female mice were irradiated with 850 rad gamma-rays and transferred with 10(7) syngeneic bone marrow cells 24 hrs later. The occurrence of cataract was examined in these animals. All the BALB/c mice showed visible lens opacification in both eyes between 113 and 149 days after irradiation. All the animals were autopsied 6 months after irradiation and examined for opacification of their lenses. The proportion of opaque lenses was 100, 7.1, 16.7 and 0% in BALB/c, CBA/Kl, C3H/HeJ and (CBA/Kl x C3H/HeJ) F1 mice, respectively. The results indicate that BALB/c mice are much more sensitive to radiation-induced cataractogenesis than CBA and C3H mice. PMID- 1748173 TI - Development and growth pattern of small hepatocellular carcinomas in woodchucks- analysis of an animal model of human hepatocellular carcinoma by ultrasonography. AB - Woodchucks are very useful animal models of human hepatocellular carcinoma. It is important to detect carcinomas in their early stage to study the pathogenesis of hepatocellular carcinoma. By ultrasonography (echogram) we found tumors less than 10 mm in diameter. Echographically all of the tumors except one were hypo-echoic in their early stages. One tumor showed a hyper-echoic pattern which grew very rapidly. Pathologically they were all well differentiated hepatocellular carcinoma and there were no differences between hypo- and hyper-echoic tumors. When volumes of tumors were less than 10 cm3 they grew very slowly but when tumors were larger than 10 cm3 their volume increased very rapidly. The ultrasonographic patterns of large tumors were iso-echoic and mosaic, as in human hepatocellular carcinoma. PMID- 1748174 TI - [Mycological examination on skin surface of cynomolgus monkeys (Macaca fascicularis)]. AB - Mycological examination on skin surface of 39 female and 35 male cynomolgus monkeys was carried out. Fungi were detected from 73 out of 74 subjects. Cladosporium was mostly predominant and the moderate predominant fungi were as follows: Acremonium, Curvularia, Arthrinium, Trichoderma, Stachybotrys, Emericella, Epicoccum, Pestalotia and Aureobasidium. However, dermatophytes or keratinophilic fungi were not isolated in this study. PMID- 1748175 TI - Mammary adenocarcinoma in a young female hypercholesterolemic rat. AB - Pathological examination of a 12-week-old female rat with hypercholesterolemia revealed mammary adenocarcinoma. Grossly, one grayish-white nodule was found in the hypoderm near the right posterior mammary gland. Histologically, the nodule was composed of variable-sized epithelial cells which lined the tubules and ducts in one to several layers, accompanied by proliferation of connective tissue in the stroma. Mitotic figures, necrosis and hemorrhage appeared frequently throughout the lesion. The tumor cells had invaded the surrounding muscular tissue. PMID- 1748176 TI - Linkage analysis of two murine polycystic kidney disease genes, pcy and cpk. AB - Two murine models of polycystic kidney disease (PKD) in humans are currently available: the infant-type cpk in mice and the adult-type pcy mutation in mice. Our linkage analysis was to determine whether these genes are allelic forms of the same gene, or infant-type and adult-type PKD resulting from homozygous and heterozygous mutation, as in the rat Cy gene. We found that the pcy gene in the mice was linked with the d gene on chromosome 9, but the cpk gene was not. A segregation test indicated that the two genes are inherited independently. This indicates that the cpk and pcy genes are not alleles and that the genetic mechanism of PKD pathogenesis in the mouse is different from that in the Cy rat. PMID- 1748177 TI - Ejaculations induced by p-chloroamphetamine (PCA) in rats, hamsters and mice. AB - The ejaculatory response induced by p-chloroamphetamine (PCA) in male rats, hamsters and mice was observed during 2 hours after the injection. The animals were treated intraperitoneally with PCA at doses ranging from 0.78125 to 160 mg/kg. The ED50 (effective dose in 50% of animals) values of PCA for the initiation of ejaculation in rats and hamsters were 1.3397 (1.0732-1.6725) and 0.1105 (0.0802-0.1522) mg/kg, respectively. On the other hand, no ejaculation was observed in any mice at any doses examined. So we concluded that there are species differences in the ejaculatory response, induced by PCA, among rats, hamsters and mice. PMID- 1748178 TI - [Comparison of the two different approaches of orchiectomy in guinea pigs]. AB - The results of orchiectomy conducted by the abdominal and scrotum routes were compared in guinea pigs. The operation time, surgical complication and incision healing were evaluated. About operation time, there was no distinct difference between two routes. In the abdominal route, the prognosis of this case was favorable. Also the healing of an incised wound was uneventful one week after the operation. While in the scrotum route, the tunica albuginea testis and the visceral vaginal tunic are thin, so that the risks of injuring the testis and/or scattering the contents of testis seem to be high. Inflammation of the scrotum was observed in 4 out of 5 guinea pigs, that were operated by scrotum route. From these results, the abdominal route method is highly recommended in the orchiectomy of guinea pigs. PMID- 1748179 TI - Linearity of cephalometric digitizers. AB - The present study aimed to develop a test procedure to diagnose and visualize errors in linearity of digitizing tablets. Errors of linearity are caused by the distortion of the x- and y-co-ordinates of the digitizing tablet. This results in a given object apparently having different dimensions when recorded on different locations of the digitizing surface. The test is performed by systematic recording of n equally spaced points from a calibrated test foil. Algorithms were developed to calculate the difference matrices DXji and DYji between expected and observed values of the co-ordinates. Three-dimensional mapping of the non linearity of the x- and y-co-ordinates was performed by the UNIRAS-geopak, a 3-D surface representative system. The tested digitizers showed varying degrees of scaling errors, fields of non-linearity, and random noise. Most digitizers allow for correction of scaling by setting of switches in the control unit. A method is suggested for correction of non-linearities by use of the DXji and DYji matrices in the digitizing programme. PMID- 1748180 TI - The aesthetic analysis of the face. AB - An analysis of the facial soft tissues is presented which permits aesthetic considerations of facial harmony and balance to be measured, and assessed quantitatively. The assessment is carried out in a practical and straight-forward manner, avoiding the measurement of angles. The visually determined Aesthetic Horizontal Line is used as the reference line, with more reliability than the Natural Head Position and more relevance to the soft tissues than Frankfort Horizontal. The analysis accurately predicts the correct position of the mandible so that the extent of orthopaedic or surgical correction necessary can be evaluated. The ideal position and angulation of the maxillary incisors are determined and established as treatment goals, to give optimal exposure of the dentition in expressive behaviour. Comparison of before and after treatment cephalograms permits quantitative assessment of aesthetic change. PMID- 1748181 TI - Relationships between jaw muscle cross-sections and craniofacial morphology in normal adults, studied with magnetic resonance imaging. AB - In 32 Caucasian adult males serial MRI scans of the jaw muscles were taken approximately perpendicular to the mean fibre direction of the jaw muscles to determine their cross-sectional areas. These areas are proportional to the maximal isometric strength of a muscle. To describe facial skeletal variation, nine angular and 21 linear cephalometric measurements were recorded, and statistically reduced by means of multiple regression and principal component analysis. Six components were extracted, rotated, and subsequently correlated with the maximal cross-sectional areas of the jaw elevators and anterior digastric muscle. Positive significant correlations were found between a linear combination of several transversal skull dimensions on the one hand, and the maximal temporalis and masseter cross-sections on the other. A negative significant correlation was found between the flexure of the cranial base and the temporalis cross-section. Surprisingly, no significant correlations were found between either anterior facial height or posterior facial height and any of the jaw muscles cross-sections. It was concluded that, in adult males with normal skull shape, relationships exist to a limited extent between craniofacial morphology and the cross-sectional areas of the jaw muscles. PMID- 1748182 TI - Cheek and lip pressure against maxillary dental arch during dummy sucking. AB - The sucking pattern and intra-oral negative air pressure were studied simultaneously with the cheek/lip pressure in 12 children when sucking a dummy. The cheek/lip pressure was measured at the canine and at the second primary molar on the right side of the upper dental arch. The cheek/lip pressure peaks followed the intra-oral negative air sucking pressure peaks continuously. In the canine region the mean value of maximum cheek/lip pressure was 54 g/cm2. The corresponding value at the second primary molar was 21 g/cm2. During dummy sucking the mean cheek/lip pressure was 3.4 times higher against the canine compared to the second molar (P less than 0.001). The intra-oral negative air pressure was approximately the same whether the cheek/lip pressure was measured at the canine or at the second primary molar. The results indicated that the circumoral muscles were especially active during dummy sucking, in addition to the cheek pressure in the canine region. PMID- 1748183 TI - Positioning control of the upper incisors in orthognathic surgery. Pre-operative planning with the Model Positioning Device and intra-operative application of the Sandwich Splint. AB - In orthognathic surgery a three-dimensional positioning of the maxilla is possible by means of the Le Fort I osteotomy and subsequent maxillary movement. In treatment planning and at the time of surgery it is very important to achieve an exact positioning of the upper incisors in relation to the upper lip and the rest of the skull. The Model Positioning Device described here allows three dimensional positioning of the upper incisors in one- or two-jaw surgery. The reference plane is the upper surface of the upper part of a semi-individually adjustable articulator. The application of the Sandwich Splint enables the three dimensional positioning of the maxilla in relation to the rest of the skull. The Sandwich Splint ensures that the vertical position of the mandible in relation to the rest of the skull above the osteotomy plane is exactly reproducible in the pre- and post-operative situation in both model surgery and at time of surgery. To this mandibular position the maxilla is positioned in three dimensions, as preplanned. The vertical dimension, which is identically reproducible before and after surgery is measured with a caliper. After surgery the mandible can be rotated into the planned new intercuspidation. PMID- 1748184 TI - The influence of orthodontic treatment on previously traumatized permanent incisors. AB - The reaction of previously traumatized teeth to orthodontic force application was investigated. Four groups of children were examined: group T comprised 56 children who encountered trauma to their maxillary incisors; group O comprised 29 orthodontic patients with intact incisors; group TO comprised 28 previously traumatized orthodontic patients; and group C served as the control group (n = 26). Orthodontic treatment was restricted to tipping movement executed only by means of removable appliances. Groups T, O, and TO were followed up longitudinally by means of clinical and radiographic examinations. In most of the cases the reported trauma occurred to teeth with completed roots and affected the crown only. Group TO presented the highest, though relatively moderate, prevalence of root resorption (27.8 per cent) and was followed by groups O and T (6.7 and 7.8 per cent, respectively) while in the control group no resorption was observed. Electrical pulp testing revealed the highest prevalence of loss of tooth vitality in group TO (7.3 per cent) in which the highest prevalence of pulp obliteration was also found. It can be concluded that the combination of trauma with orthodontic tipping renders the teeth more susceptible to complications, especially to root resorption and loss of vitality. PMID- 1748185 TI - Relationship between craniomandibular dysfunction and pattern of speech sound production in a series of first-graders. AB - This report investigates associations between prevalence of functional disturbances of the masticatory system and speech disorders. The subjects were 157 children referred for speech therapy to the hospital and a control group all 130 first-graders at two elementary schools, mean age 7 years 6 months. During clinical examinations, signs and symptoms of TMJ dysfunction were recorded by the same dentist. Articulatory speech disorders were diagnosed by the same phoniatrician using the Remes Articulatory Test (Remes, 1975) for the Finnish language. The results showed that in the hospital referral group the mean value for maximal opening was smaller while laterotrusion movements and maximal protrusion of the mandible were larger than in the control group. The study group also more often had CM disorders and occlusal interferences than children of the first grade sample. In the present data, a higher frequency of subjective symptoms and several clinical signs of CMD were related to certain articulatory speech disorders. Risk of having too anteriorly-produced sounds, mainly 's' sounds, decreased with advancing age in 6-8-year-old children. In conclusion, expression of both craniomandibular disorder and disorders in speech sound production seem to a considerable extent to reflect immaturity of fine motor control of the orofacial muscles in 6-8-year-old children. PMID- 1748186 TI - Examination of Chinese NiTi wire by a combined clinical and laboratory approach. AB - Chinese NiTi wire was compared with Nitinol and stainless steel wires in a combined laboratory and clinical examination. In the laboratory test, the loading and unloading-deflection properties of the wires were determined in a three-point bending test and their surface properties were studied in a scanning electron microscope. This test attempts to simulate a common clinical situation. The NiTi material showed a non-linear force-deflection relationship. The increase in force from 1 mm deflection and onwards was very slow and the force delivered during unloading from large deflections was almost constant. This behaviour was somewhat different for smaller downward deflections of NiTi wires. Plastic deformation was insignificant. The clinical study confirmed the laboratory results obtained, characterizing a wire material much superior to stainless steel and even superior to Nitinol for alignment purposes. In clinical use, however, the rate of fractures of NiTi wires turned out to be unsatisfactorily high. This disadvantage was not predicted by the three-point bending test. Scanning electron microscopy revealed surface defects and non-metallic inclusions in fractured NiTi wires. A combination of a bending test simulating a clinical situation and surface examination is recommended when new wire materials are to be tested. PMID- 1748187 TI - Spontaneous changes in the rotation of premolar teeth from eruption until the established dentition. AB - The aim of this study was to investigate whether the rotation of teeth changed from the point of eruption until the established dentition. The first 50 cases with adequate records enrolled in the Belfast Growth Study were selected, and the premolar rotation was measured at the point of eruption and again at age 15 in the established dentition. All premolars in a quadrant with early loss of the deciduous predecessors, early loss of the first permanent molars or absence of premolars, were disregarded. The results showed that the second premolars in both the upper and lower arches which erupted rotated had a tendency to improve over the observed period. Upper and lower first premolars which erupt rotated show the same tendency to improve, but to a lesser extent and less frequently than the second premolars. There seemed to be cases where a premolar deteriorated over the period, especially the first premolars. PMID- 1748188 TI - The effect of orthognathic surgery on head posture. AB - Changes in resting head and neck posture were studied in 201 patients following five different orthognathic surgery procedures: (1) LeFort I osteotomy for superior repositioning (intrusion) of the maxilla (n = 45); (2) bilateral sagittal split ramus osteotomy for mandibular advancement (n = 78); (3) mandibular setback (n = 19); (4) combined maxillary intrusion and mandibular advancement (n = 46); (5) combined maxillary intrusion and mandibular setback (n = 13). Head and neck posture were measured on standardized serial cephalograms taken in natural head position prior to, immediately after, and 1 year after surgery for each subject. Immediately after surgery, there was flexion of the head as measured by the craniovertical and craniocervical angles in all of the groups except the mandibular setback group, which showed little change. By 1 year post-surgery, the mean craniovertical and craniocervical angles were approximately the same as before surgery in the groups with one-jaw surgery. Statistically significant head flexion at 1 year (P less than 0.05) was observed in the combined maxillary intrusion and mandibular advancement group, and with maxillary intrusion plus mandibular setback, there was a trend toward persistent flexion. Neck posture showed no significant short- or long-term changes in any of the surgical groups. PMID- 1748189 TI - Ankylosis of primary molars--a future periodontal threat to the first permanent molars? AB - Most infra-occluded and ankylosed primary molars with a permanent successor will exfoliate normally. Continuous supervision of occlusal development and radiographic control of normal root resorption have been recommended. The decreased height of the alveolar bone level at the site of the infra-occluded primary molar has been reported to normalize after the eruption of the permanent successor. However, opinions that infra-occlusion of primary molars entails a risk of future periodontal damage to the first permanent molars have been presented. The aim of this study was to perform a long-term follow-up of the alveolar bone level mesial to the first permanent molars after spontaneous exfoliation or necessary extraction of the infra-occluded second primary molars. The material consisted of 143 permanent molars adjacent to 119 infra-occluded primary molars and 24 normal contralateral primary molars in 68 individuals. The subjects were re-examined about 8 years after the exfoliation or extraction of the infra-occluded second primary molars. The subjects were examined both clinically and radiographically. Alveolar bone level mesial to the first permanent molars was measured in bite-wing radiographs. All but two permanent first molars showed a normal alveolar bone level mesially. In two first permanent molars where the primary molar was extracted, mesial approximal bone loss amounted to 4 and 3 mm, respectively, but no pocket formation was found. Infra occlusion and ankylosis of primary molars does not constitute a general risk of future alveolar bone loss mesial to the first permanent molars. The general treatment recommendation to await normal exfoliation and eruption of successors remains valid. PMID- 1748190 TI - A postero-anterior cephalometric evaluation of adult open bite subjects as related to normals. AB - Reduced nasal airflow can be the result of enlarged adenoids, hypertrophic turbinates, severely deviated nasal septum, or even narrow nasal cavities. The question of whether the width of the nasal cavity may influence certain facial dimensions examined on the postero-anterior cephalometric X-ray was evaluated through the study of two different groups of subjects. Possible intercorrelations between some other frontal dimensions were also examined in these subjects. The first group consisted of 15 males and 22 females aged from 17 to 25 years diagnosed as having an anterior open bite of at least 2 mm. The second group consisted of 20 males and 16 females aged from 19 to 25 years with a normal Class I skeletal and dental pattern. Postero-anterior cephalometric X-rays were taken for all individuals and the following dimensions were measured: facial width, nasal width, maxillary width, mandibular width, nasal height, and lower facial height. Statistical analysis was performed for the primary linear measurements as well as for certain ratios. Nasal height and lower facial height were found to be significantly increased in both males and females of the open bite group. The ratios of nasal width to lower face height, as well as nasal width to nasal height, were found to differ significantly only between open bite and normal females, being higher in the latter group. PMID- 1748191 TI - Ligature wires and elastomeric rings: two methods of ligation, and their association with microbial colonization of Streptococcus mutans and lactobacilli. AB - Twelve orthodontic patients undergoing treatment with fixed appliances took part in the present study. In all patients elastomeric rings were used for ligation on one side of the dental arch midline, whereas steel wires were used on the opposite side. The number of micro-organisms in samples of plaque, taken from the labial surface of the upper lateral incisors, was recorded on five occasions during treatment. In samples of saliva, the numbers of Streptococcus mutans and lactobacilli were recorded on the same occasions. This registration was also made on two occasions before insertion of the fixed appliance, and 6 weeks after the period of active treatment. The results showed that, in the majority of patients, the incisor which was attached to the arch-wire with an elastomeric ring, exhibited a greater number of micro-organisms in the plaque than the incisor ligated with steel wire. Following insertion of fixed appliances the number of S. mutans and lactobacilli in saliva increased significantly. Variations in the number of micro-organisms in the saliva during active treatment were not reflected in any relative increase or decrease in microbial colonization on either steel ligatures or elastomeric rings. The use of retainers after active treatment was not associated with increased numbers of micro-organisms in the saliva. PMID- 1748192 TI - An atlas of the prenatal mouse brain: gestational day 14. AB - A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer. PMID- 1748193 TI - Changes in blood-brain barrier permeability are associated with behavioral and neurochemical indices of recovery following intraventricular adrenal medulla grafts in an animal model of Parkinson's disease. AB - Intraventricular adrenal medulla grafts were found to produce dissociable effects on rotational behavior induced by amphetamine and apomorphine in rats with unilateral striatal dopamine depletions. Some animals showed a decrease in the behavioral response to apomorphine, some showed a decrease to amphetamine, and some showed a decrease to both amphetamine and apomorphine. Using in vivo microdialysis, the experiments reported demonstrate that in animals with decreased rotational behavior, assessed with either amphetamine or apomorphine, there was an increase in the permeability of the blood-brain barrier to dopamine. The increased blood-brain barrier permeability was visually confirmed with horseradish peroxidase. The extent of the blood-brain barrier disruption, however, was greater in animals with a decreased response to amphetamine. Animals that exhibited decreased amphetamine-induced turning after adrenal medulla grafts also had a greater amphetamine-stimulated increase in striatal dopamine and greater extracellular striatal dihydroxyphenylacetic acid concentrations compared to controls and animals with a graft-induced decrease in the response to apomorphine. We conclude that more than one mechanism is involved in mediating the behavioral effects of adrenal medulla grafts. PMID- 1748194 TI - Do propriospinal projections contribute to hindlimb recovery when all long tracts are cut in neonatal or weanling rats? AB - Lateral hemisection lesions separated by 1 to 3 spinal segments were made on opposite sides of the mithoracic spinal cord in 1-month-old (N = 15; weanling operates) and newborn albino rats (N = 16; neonatal operates). Hindlimb behavior was assessed between 1 and 6 months p.o. for both groups of operates using a protocol and rating system that have previously proved effective in differentiating behavioral recovery of the hindlimbs as a function of age of spinal transection. In addition, at the conclusion of behavioral testing, operates received spinal injections of [3H]proline and HRP caudal to the spinal lesions to determine if lesions were complete and if neurons within the region between the two lesions (interlesion zone) projected into the caudal spinal cord. In both groups of operates, neurons were retrogradely labeled within the interlesion zone bilaterally, primarily in laminae VII-VIII. When both lesions were complete lateral hemisections in weanling operates, little behavioral recovery was observed, similar to complete spinal cord transection (N = 3). However, much greater behavioral recovery was seen, including supporting reactions and locomotor responses, when one or both lesions spared axons along the ventrolateral rim of the white matter. Neurons were retrogradely labeled in the brain stem reticular formation (N = 12) in these cases. All lesions were complete lateral hemisections in neonatal operates but much greater behavioral recovery was seen than in weanling operates with the same lesions, including supporting, placing, and locomotor responses. In an additional group of eight neonatal operates, the spinal cord rostral to the spinal hemisections was transected at 1 month of age. Supportive, placing, and locomotor responses were seen immediately after recovery from anesthesia and responses returned to pretransection levels in six of eight operates over the 10-day survival period. Fink-Heimer impregnation showed that degeneration argyrophilia from the transection bilaterally filled the interlesion zone but little argyrophilia was seen caudal to this region. Our results indicate that an intact propriospinal circuit remains in both neonatal and weanling operates but does not appear to contribute to hindlimb response development or recovery. The greater behavioral recovery in neonatal operates appears due to intrinsic connections (doral root, interneuronal) continuing to be able to drive the spinal circuitry underlying the spared behaviors. PMID- 1748195 TI - Correlative electrophysiological and behavioral evaluation following L5 lesions in the cat: a model of spasticity. AB - The present work developed an animal model of hindlimb spasticity by analyzing the electrophysiological and behavioral consequences of L5 spinal cord lesions in cats. In chronically lesioned animals (1 to 6 months), the L7-S1 dorsal roots were stimulated and evoked potentials were recorded from hindlimb flexor and extensor motor nerves. Following lateral hemisection, the monosynaptic responses were 2-5 times larger (for voltage-time integral and for amplitude) on the ipsilateral side than those from the contralateral side or from control animals. Half-widths, rise-times, and latencies of the monosynaptic responses were the same on both sides. Behavioral signs of spasticity, including hypertonia and increased deep tendon reflexes, were displayed from the ipsilateral hindlimb following lateral hemisection. With lateral hemisection or with extensive dorsal quadrant lesions, hopping and proprioceptive placing reflexes were abolished; these behavioral observations impart functional significance to physiological and anatomical studies of a mid-lumbar center considered to be important for movement control. The present model represents the first demonstration of a statistically significant correlation between electrophysiological and behavioral observations of spasticity for animals with a lateral hemisection. These correlations demonstrate the utility of behavioral screening of animals for subsequent neurophysiological analyses. This facilitates the investigation of cellular events underlying spasticity and of strategies for its relief with tissue repair techniques affecting local circuitry involved in spasticity. PMID- 1748196 TI - Neurite outgrowth on postmortem human brain cryostat sections: studies of non Alzheimer's and Alzheimer's tissue. AB - An in vitro assay to test for regional differences in neurite growth-promoting and growth-inhibiting factors in tissue sections of CNS tissue has been adapted to the use of postmortem human brain tissue. Frozen sections of the temporal lobe from victims of Alzheimer's disease were used as substrates for sympathetic neurite outgrowth in tissue culture. Tissue sections from a non-Alzheimer's brain were used as a control. Both explanted chick sympathetic ganglia and dissociated chick sympathetic neurons were cultured for 3 to 5 days on tissue sections in the presence of exogenous nerve growth factor. The dichotomy between gray and white matter portions of the tissue sections in supporting neurite outgrowth that was previously reported for fresh frozen human brain tissue was also found to persist in postmortem tissue. In addition, the total neurite outgrowth from explanted sympathetic ganglia was found to be significantly less on postmortem sections when compared with previous results obtained from fresh frozen tissue samples of epileptic tissue. Dissociated neurons exhibited neurite outgrowth on Alzheimer's sections that showed preferential growth on blood vessel segments but no affinity for senile plaques. The results suggest that there is some decline in the neurite growth-promoting ability of cortical gray matter obtained from postmortem-derived brains when compared with fresh tissue and that senile plaques do not represent sites of neurite stimulation in this in vitro system. PMID- 1748197 TI - A carbohydrate polymer that effectively prevents epidural fibrosis at laminectomy sites in the rat. AB - We demonstrate that a carbohydrate polymer, designated GL402, effectively inhibits epidural fibrosis in a rat laminectomy model. A total laminectomy in Lewis rats was performed at lumbar vertebrae 3 and 5. GL402 or phosphate buffer solutions in gelatin sponges were applied to the laminectomy sites. Epidural fibrosis was measured, using a double-blind protocol, 2 weeks postoperatively either by gross anatomical evaluation (blunt dissection) or by histological evaluation. Local application of GL402 produced nearly complete inhibition of epidural fibrosis, whereas extensive scar formation and bone growth occurred after local application of buffer or other purported anti-fibrotics. In laminectomy sites treated with GL402 the dura mater was essentially free of adhering fibrosis and bone growth was dramatically decreased. With reduction of postlaminectomy fibrosis, the spinal nerve roots are more mobile and therefore may be less prone to recurrent nerve root compression. The dramatic reduction of epidural fibrosis by GL402 will make reoperative disc surgery safer due to greater accessibility of the laminectomy site. This compound may be useful in preventing surgical adhesions in other sites as well. PMID- 1748198 TI - Long-term adrenalectomy causes loss of dentate gyrus and pyramidal neurons in the adult hippocampus. AB - A growing literature suggests that the hippocampus can be damaged by glucocorticoids, the adrenal steroids secreted during stress. Thus, considerable interest was generated by recent reports that prolonged elimination of glucocorticoids by adrenalectomy (ADX) damages hippocampal dentate gyrus neurons. To date, this phenomenon has only been observed in rats of peripubertal age or younger; moreover, reports differ considerably as to the magnitude of the damage induced. Therefore, we examined this issue in rats ADXd at 5 months of age. Three months later, there was a significant 26% loss of dentate neurons in a subset of rats. In agreement with these previous reports, this subset had attenuated weight gain and electrolyte imbalances, suggestive of complete removal of the adrenals and accessory adrenal tissue. As a novel observation, we also observed significant (19%) loss of CA4 pyramidal neurons. Thus, both severe under- or overexposure to glucocorticoids can be deleterious to a number of hippocampal neuron types. PMID- 1748199 TI - Age-related sensitivity to kainate neurotoxicity. AB - Domoate, a glutamate analog, is believed to be responsible for a seafood poisoning incident that caused acute neurological disturbances and chronic memory impairment in some victims, with the incidence of mortality and neuropsychological morbidity being highest among the aged. Domoate expresses neurotoxic (excitotoxic) activity in vitro by an action at the kainate subtype of glutamate receptor, and when administered to adult rats, it mimics kainate in causing status epilepticus and a severe seizure-brain damage syndrome. Because domoate is exceedingly expensive, we explored the feasibility of using kainate to study the age-linked features of domoate neurotoxicity. We administered kainate subcutaneously in various doses to young (5-6 months), middle-aged (12-13 months), and old (22-25 months) rats and found the middle-aged and old rats significantly more sensitive than young rats to the neurotoxic actions of kainate. Low doses of kainate, which were nontoxic to young rats, frequently triggered status epilepticus, associated brain damage, and precipitous death in old rats. Middle-aged rats were more sensitive than young rats, but less sensitive than old rats to kainate neurotoxicity. These results suggest that the kainate-treated rat may be a useful model for studying mechanisms underlying age related aspects of the human domoate neurotoxic syndrome. PMID- 1748200 TI - Induction of axon growth into Schwann cell implants grafted into lesioned adult rat spinal cord. AB - Polymerized collagen rolls enclosing Schwann cells (SCs) raised in culture were grafted into cystic cavities formed after lesioning the thoracic spinal cord of adult rats. Axons were already present within the graft by 14 days after implantation and both ensheathed and myelinated axons were numerous by 28 days. This axonal ingrowth was maintained over longer survival periods. The axons within the graft always appeared related to Schwann cells. Acellular collagen rolls did not show axonal ingrowth. These Schwann cell-collagen implants resemble peripheral nerve grafts in their ability to induce axonal regeneration into the graft. PMID- 1748201 TI - Relationship of glia to GnRH axonal outgrowth from third ventricular grafts in hpg hosts. AB - The homozygous mutant hypogonadal (hpg) mouse lacks a functional gene for the neuropeptide gonadotropin releasing hormone (GnRH). The consequence of this defect is an infantile reproductive tract in adulthood. This condition can be reversed by the implantation of normal fetal preoptic area tissue that contains GnRH neurons. Reversal is always preceded by the outgrowth of GnRH axons into the host target tissue, the median eminence, by a stereotyped pathway. In the current experiments we investigated the cellular nature of the path taken by early emerging GnRH axons focusing on their relationship with astrocytic components and with the specialized ependymal population of this area, the tanycytes. In control tissue glial fibrillary acid protein (GFAP) immunoreactivity was confined to the exterior of cerebral blood vessels and glial limitans. Both GFAP and vimentin, another intermediate filament protein, marked the specialized ependymal cells of this region, the tanycytes. There was a robust reactive astrocytic response to the injury of transplantation in both the donor and host tissue within 5 days of implantation and the reactive astrocytes persisted for 60 days. These cells were GFAP-positive and were present in many areas of the host along the cannula tract and not confined to the area of GnRH axonal outgrowth. Vimentin, another intermediate filament, marked only the specialized ependymal cells of this region, the tanycytes, in both control and grafted tissue. Despite the profound reactive gliosis, GnRH axons were shown to exit the implant as early as 5 days after grafting suggesting that the gliotic process did not constitute a barrier to this phenomenon. At the light microscopic level, double label immunocytochemical studies did not reveal any specific association between GFAP or vimentin-positive cellular processes and these pioneer GnRH fibers. However, since normal GnRH axons had been reported to travel in tanycytic channels through the medial basal hypothalamus we reinvestigated the pattern of early emerging GnRH axons at the ultrastructural level. With this higher resolution, GnRH axons were found adjacent to glial elements along their entire traverse from the graft host interface, through the host basal hypothalamus to their termination on the hypophysial portal capillaries. At the interface, GnRH-positive axons appeared to exit via glial channels similar to those described in other developing and regenerating systems. In the host, GnRH immunoreactive axonal profiles were surrounded by glial processes though the latter could not be further defined as tanycytic or astroglial. Other, immunonegative, axons were frequently seen in axonal bundles or fascicles and not necessarily in contact with glia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1748202 TI - The role of Schwann cells in the regeneration of peripheral nerve axons through muscle basal lamina grafts. AB - Evacuated muscle is a possible substitute for nerve autografts in the repair of damaged peripheral nerves. Previous experiments have shown that killed or evacuated muscle grafts are as effective as nerve autografts for bridging gaps of up to 4 cm between proximal and distal nerve stumps. Evacuated muscle grafts are made of extracellular matrix components, which are good substrates for axon growth in vitro. However, experiments in vivo have generally demonstrated that live Schwann cells are essential for successful axon regeneration. In the present experiments we have used immunohistochemical techniques with anti-S100 and anti neurofilament antibodies to visualize axon growth and Schwann cell migration into muscle grafts over the first 10 days following grafting. We only saw axons growing into grafts accompanied by Schwann cells, and most though not all Schwann cells were associated with axons. Schwann cell migration from the proximal stump in association with axons was much faster and more extensive than from the distal stump. We examined muscle grafts over the first 20 days after grafting by electron microscopy. Regenerating axons were always associated with Schwann cells, which were mostly in the basal lamina-lined tubes left by the evacuated myofibrils. A comparison between evacuated muscle grafts and grafts in which the muscle had been killed but not evacuated revealed that 7 days after grafting there were more than twice as many regenerated axons in and distal to the evacuated grafts, but that by 20 days the numbers of axons were similar in the two groups. PMID- 1748203 TI - Factors influencing survival of transplanted embryonic motoneurones in the spinal cord of adult rats. AB - The survival of transplanted embryonic motoneurones in the initially intact spinal cord of adult rats was studied and compared to that previously observed in the motoneurone-depleted cord. Embryonic (ED 11-12) spinal grafts prelabeled with 5-bromo-2'-deoxyuridine (BrDUr) were placed in the intact lumbar cord of the hosts. To provide a target for grafted embryonic motoneurones and to guide their axons to it, the contralateral extensor hallucis longus (EHL) muscle with its nerve attached was transferred paravertebrally. The nerve stump was implanted in the cord at the site of transplantation. Eight to 14 weeks later BrDUr-labeled motoneurone-like cells had migrated outside the grafts into the host's neuropil, preferentially into the anterior horn. Following injection of HRP into the implanted EHL muscle 6-17 weeks after transplantation a few retrogradely labeled motoneurones were seen in the host's anterior horn around the grafts. The lumbar cord of the rats with neuromuscular implants but without embryonic grafts had no retrogradely labeled cells. However, most animals, both with and without embryonic grafts, had retrogradely labeled motoneurones in the thoracic cord, which may contribute to the reinnervation of the implanted muscle. Thus, although some embryonic motoneurones can survive, migrate into the proper location, and probably innervate a host muscle when transplanted into the intact spinal cord, their number was significantly fewer than that in the motoneurone-depleted cord. The results show that reduction of the host's motoneurone pool increases chances of their survival. PMID- 1748204 TI - Contingent tolerance to carbamazepine is associated with lowering of amygdala kindled seizure thresholds. AB - Amygdala-kindled seizure thresholds were studied in animals which were or were not tolerant to the anticonvulsant effects of carbamazepine. The seizure threshold was defined as the lowest current that elicited a major motor seizure (stage 3 or greater). Amygdala-kindled rats received carbamazepine, once daily, either before each electrical stimulation (carba-before) or after each stimulation (carba-after). The rats given carbamazepine before, but not after, each once-daily kindling stimulation became tolerant to its anticonvulsant effects. Following this manipulation, seizure thresholds were redetermined in both groups of animals while medication-free. The carba-before (i.e., tolerant) animals showed a decreased seizure threshold, while the carba-after (i.e., nontolerant) animals showed no change. Tolerance to carbamazepine was reversed by giving the rats kindled seizures for a period of 7 days without drug; nontolerant animals received the same stimulation and seizures. When seizure thresholds were reevaluated, the carba-before animals (now not tolerant) had returned to their pretolerance values, while the carba-after group again showed no change. This effect of carbamazepine tolerance and its reversal being associated with respective decreases and increases in basal seizure threshold was replicated two more times. In each case the change in the generalized seizure threshold mirrored the change in responsivity of the animals to carbamazepine. These findings, consistent with the formulations of Siegel regarding conditioned compensatory response mechanisms mediating contingent drug tolerance, may have important clinical and theoretical implications. PMID- 1748205 TI - Effect of ischemia and reperfusion in vivo on energy metabolism of rat sciatic tibial and caudal nerves. AB - Our model of severe nerve ischemia consistently results in extinction of the compound nerve and muscle action potentials (NAP; CMAP) within 30 min. Since impulse transmission may depend on nerve energy metabolism (NEM), we studied the effects of ischemia with reperfusion on sciatic-tibial nerve NEM in vivo and compared these results with NEM of this nerve in deoxygenated Ringer's solution in vitro and postmortem. Ischemia for 30 min postmortem or in deoxygenated Ringer's solution resulted in marked depletion of adenosine triphosphate (ATP) and creatine phosphate (CP) and an increase in lactate (LAC) of sciatic-tibial nerve of adult male Sprague-Dawley rats. In vivo ischemia for up to 3 h to sciatic-tibial nerve was sufficient to extinguish CMAP but not NAP and did not deplete ATP, CP, or GLU nor did it increase LAC. Ischemia sufficient to extinguish NAP resulted in reduction of energy substrates to about 50% of resting. Muscle fails to conduct impulses before nerve and in vivo reductions of energy substrates are milder than in vitro changes. These changes are explainable in terms of energy requirements and supply. These findings support an energetic basis of ischemic conduction failure. PMID- 1748206 TI - Intraspinal sprouting of calcitonin gene-related peptide containing primary afferents after deafferentation in the rat. AB - The occurrence of sprouting in the spinal cord in response to denervation has been a subject of debate. To test for sprouting of primary afferent fibers after denervation, rats were unilaterally deafferented for 35 days (chronic side) by dorsal rhizotomies performed from T2 to T8 and T10 to L5, thus isolating or sparing the T9 root. The contralateral T9 root was spared by a similar surgery 5 days (acute side) prior to sacrifice. The survival time on the chronic side presumably allows intraspinal sprouting of T9 primary afferents to occur whereas the time on the acute side does not. To test for sprouting of primary afferents, it is necessary to identify these nerve processes. Calcitonin gene-related peptide (CGRP) immunoreactivity has been localized to a subpopulation of primary afferent nerve processes and their terminals within the dorsal horn. Therefore, immunohistochemical methods were used to determine the distribution of CGRP immunoreactivity in laminae I and II on both sides of the spinal cord. Using image analysis, there was an increase of 153 to 704% in the density of CGRP immunoreaction product on the chronic side compared to the acute side in the spared segment. This difference is statistically significant. Furthermore, the increased density on the chronic side extended two segments cranial and two segments caudal to the spared root segment. No difference was found in the laminar distribution between sides. These data support the hypothesis of primary afferent sprouting following spinal cord denervation. PMID- 1748207 TI - Development of cholinesterase histochemical staining in cerebellar cortex: transient expression of "nonspecific" cholinesterase in Purkinje cells of the nodulus and uvula. AB - Patterns of "nonspecific" cholinesterase (ChE) and acetylcholinesterase (AChE) activity were studied in developing rat cerebellar cortex by enzyme histochemistry and light and electron microscopy. Three types of ChE histochemical reaction product were observed in cerebellar cortex: (i) ChE is found in capillary endothelium throughout the cerebellum. Capillary ChE staining is present by the time of birth and continues into adulthood. (ii) ChE is found in radial glial fibers and their parent cell bodies, the Golgi epithelial cells. Radial glial fiber staining is mot intense during the first 3 weeks of postnatal life. (iii) ChE is found in Purkinje cells of the nodulus and ventral uvula. No ChE staining of Purkinje cells was seen in other parts of the cerebellum. ChE staining of Purkinje cells appears to be transient, first appearing at Postnatal Day 2 (P2), reaching peak intensity at P7-9, and decreasing to adult levels by P16. AChE activity displays a pattern markedly different from ChE, with staining in deep cerebellar nuclei, in putative mossy fiber terminals, and in Golgi neurons of cerebellar cortex. No evidence was found for transient AChE staining in Purkinje cells in any part of the cerebellum. The function of transiently expressed ChE activity in developing Purkinje neurons is unknown, but may be related to reorganization of cerebellar cortical circuitry associated with growth of mossy fiber afferents. PMID- 1748208 TI - Co-grafts of embryonic dopamine neurons and adult sciatic nerve into the denervated striatum enhance behavioral and morphological recovery in rats. AB - We have recently demonstrated that a diffusible factor(s) derived from explanted adult rat sciatic nerve can increase the number and neurite outgrowth of embryonic rat dopamine (DA) neurons in culture. The present study extends this finding to compare DA neuron-sciatic nerve co-grafts to grafts of DA-rich neural tissue alone for behavioral and morphological effects in rats with unilateral nigrostriatal lesions of the DA pathway. Our results indicate that the presence of a co-grafted segment of sciatic nerve increased the likelihood of rapid behavioral recovery and promoted complete recovery mediated by small grafts that yielded only modest behavioral changes in the absence of co-grafted nerve. These behavioral effects were accompanied by a modest increase in survival of grafted tyrosine hydroxylase-positive neurons in the striatum and a more pronounced increase in the area and density of striatal reinnervation provided by grafted DA neurons in co-grafted animals. This evidence supports the view that a diffusible product of explanted peripheral nerve acts as a growth-promoting factor for embryonic DA neurons and that the presence of this factor augments the behavioral efficacy of grafted DA neurons. PMID- 1748209 TI - The effects of NGF and fetal cell transplants on spatial learning after intradentate administration of colchicine. AB - This study was performed to assess the effects of NGF infusion alone or in combination with fetal hippocampal transplants on recovery of function after damage to hippocampal dentate granule cells. Two groups of male Fischer-344 rats received bilateral infusions of colchicine (COLCH; 2.5 micrograms/site) or artificial cerebrospinal fluid (ACSF; 0.5 microliter) through chronic indwelling cannulae into the dentate gyrus. At the time of COLCH injection, a unilateral intracerebroventricular (ICV) cannula was implanted. One week later, when animals were tested in activity chambers for 60 min, COLCH-treated rats showed a significant increase in spontaneous locomotor activity. Two weeks after COLCH treatment, animals were assigned to various post-treatment groups and received 1.0 microliter of rat fetal hippocampal cell suspensions (ED-17 or 18) or Earle's basic salt solution in the same site as previous hippocampal infusions. Modified Alzet miniosmotic pumps (0.25 microliter/h) containing NGF (10 ng/microliter) or ACSF with cytochrome C (20 ng/microliter) were implanted subcutaneously and attached to the previously implanted ICV cannulae. The animals were tested for learning ability in a Morris water maze task starting 6 or 12 weeks post-COLCH. During both test periods, COLCH lesions significantly impaired acquisition and retention. At 6 weeks postlesion, NGF treatment ameliorated this COLCH-induced behavioral deficit while the presence of transplants did not ameliorate the COLCH induced learning deficit. COLCH/transplant/NGF-treated rats performed better than both COLCH-lesioned rats with or without transplants. At 12 weeks postlesion COLCH-induced behavioral deficits were not ameliorated by NGF or transplants. Morphological examination performed after behavioral testing confirmed the presence of viable transplants and COLCH-induced granule cell loss. Exogenous NGF infusions appeared to have no effect on the morphological measures taken. These data demonstrate a time-dependent facilitative effect of exogenously applied NGF on functional deficiencies produced by experimentally induced neurodegeneration in the dentate gyrus of the hippocampus. PMID- 1748210 TI - Functional recovery following direct or graft repair of nerve gaps in the rat. AB - The tibial functional index has been employed to assess functional recovery in rats following nerve repair by direct coaptation under tension or by grafting. Recovery after direct repair of small to moderate gap sizes was better than that after grafting. PMID- 1748211 TI - Incorporation of circulating fibronectin into various tissues during sepsis: colocalization with endogenous tissue fibronectin. AB - We studied the plasma clearance and tissue incorporation of intravenously infused purified human plasma fibronectin into various tissues during a period of acute lung vascular injury induced by lethal postoperative bacteremia in sheep. Lung, liver, spleen, and heart tissue were examined for both endogenous sheep tissue fibronectin as well as the experimentally infused human fibronectin using dual label immunofluorescence. Awake sheep (n = 4) received a postoperative iv infusion of 5 x 10(9) live Pseudomonas over a 60-min infusion interval. Bacterial challenge was started 2 hr after starting the iv fibronectin infusion of purified human plasma fibronectin (100 mg iv bolus; 4 hr iv at 100 mg/hr). Human fibronectin displayed a biphasic rate of clearance from the plasma with entrance into lymph. Human fibronectin readily incorporated in all tissues studied, including the lung which was the focus of vascular injury. Analysis of tissue sections by dual-label immunofluorescence indicated that the exogenous human fibronectin colocalized with the endogenous sheep fibronectin. Thus, the plasma fibronectin concentration may influence the lung vascular barrier due to its incorporation into the tissue pool of fibronectin. Moreover, the plasma may serve as a reservoir for soluble fibronectin which can enter and colocalize with the insoluble tissue pool of fibronectin in various tissues. PMID- 1748212 TI - Macromolecular composition of the myotendinous junction. AB - The macromolecular composition of the myotendinous junction of the rat Achilles tendon was investigated. Heparan sulphate, chondroitin sulphate, and/or dermatan sulphate could be detected in the terminal processes of the muscle cells, but neither heparin nor keratan sulphate was present. The presence of hyaluronic acid was also questionable. High concentrations of sulphate containing glycosaminoglycans could be demonstrated both in the sarcolemma membranes and extracellular region. The main collagenous component in the myotendinous junction was type I collagen. Also small amounts of type III collagen was found at the myotendinous interface. In addition, high concentrations of fibronectin was present on the muscle cell surfaces of the junction. These results showed that myotendinous junction is histochemically and immunohistochemically a highly specified area rich in various polysaccharides. The high concentration of the polysaccharides in the myotendinous interface may increase the adhesive force between the muscle cell membrane and tendineal collagen fibrils and, by this way, it may be important in improving the elastic buffer capacity of the junction against loading. PMID- 1748213 TI - Comparative activity of doxorubicin and its major metabolite, doxorubicinol, on V79/AP4 fibroblasts: a morphofunctional study. AB - Doxorubicin (DXR), an anthracycline antineoplastic drug, is mainly metabolized to the C-13 dihydroderivative doxorubicinol (DXR-ol), which displays cytotoxic activity on various cell lines. To better characterize the cytotoxic activity of this metabolite, we have studied the effect of DXR (0.1-10 micrograms/ml) or DXR ol (1-100 micrograms/ml) on the transformed fibroblast cell line V79/AP4 by means of the clonogenic assay, cytofluorescence, and light and electron microscopy. Both DXR and DXR-ol displayed a dose-dependent inhibition of colony formation with an IC50 factor DXR-ol/DXR of 19.5. A striking nuclear fluorescence was observed after DXR but not after DXR-ol. A low number of mitoses and a decrease in nucleoli staining affinity were the most evident alterations induced by DXR. Electron microscopy showed both nuclear and cytoplasmic changes in DXR treated cells: nucleolar segregation, cytoplasmic vacuoles, and mitochondrial swelling with dense needle-shaped material were observed. Exposure to formic acid confirmed the calcific nature of the mitochondrial bodies. Only the highest dose of DXR-ol brought about nuclear and cytoplasmic ultrastructural changes similar to those induced by DXR. Our data describe new in vitro findings on the cytotoxicity and morphological alterations induced by both DXR and DXR-ol, with a lower activity of DXR-ol against V79/AP4 fibroblasts. PMID- 1748214 TI - Mechanism of liver injury following ischemia. AB - To clarify whether ischemic liver injury is due to ischemia itself or reperfusion, histopathological and functional changes in the liver were examined before and after liver ischemia in rats with porto-systemic collateral channels. Effects of oxygen-derived free radical scavengers or an inhibitor of platelet aggregation on development of ischemic liver injury were also examined. Liver ischemia was produced by ligation of the portal vein and hepatic artery at liver hilum for 1 hr. The primary lesion of ischemic liver injury was cloudy swelling of liver cells in the periportal and midzonal regions; it developed during ischemia. The cloudy swelling of liver cells induced uneven distribution of sinusoidal blood flow after reperfusion, and consequently individual liver cell necrosis and focal hepatocellular necrosis in the midzonal regions developed later. Elevation of cytoplasmic enzyme activities in the serum after reperfusion was due to leakage across the damaged plasma membrane of liver cells. The treatment with superoxide dismutase, catalase, or heparin had not altered the liver injury that was attributed to ischemia, biochemically and histologically. These results suggest that ischemic liver injury is due to liver cell damage developed during ischemia, and that the ischemic liver injury is not alleviated or prevented by superoxide dismutase, catalase, or heparin. PMID- 1748215 TI - Helicobacter pylori affects the quality of experimental gastric ulcer healing in a new animal model. AB - Helicobacter pylori has been implicated in the genesis of human gastritis, dyspepsia, and peptic ulcers. However, its influence in the quality of experimental gastric ulcer healing has not been previously investigated. Standardized gastric fundic ulcers were produced in 50 male Sprague-Dawley rats (150-200 g) by a 4 mm in diameter focal, serosal application of 100% acetic acid. Thirty rats were administered 2 ml H. pylori suspension (urease producing, ATCC 43504) in normal saline (10(8) CFU/ml) 2x/day for 7 days. Twenty rats (controls) received 2 ml normal saline 2x/day for 7 days. Gastric ulcer surface area was measured under a dissecting microscope and mucosal specimens were obtained for qualitative and quantitative histology. No gross or microscopic duodenal abnormalities were identified at sacrifice. Ninety percent of control rats showed grossly and microscopically entirely healed ulcers. The remaining 10% showed partially reepithelialized ulcers (area, 0.78 to 1.77 mm2; mean, 1.27 +/- 0.7 mm2). The grossly "healed" mucosa demonstrated marked dilatation of gastric glands lined with mature surface epithelial cells. Parietal cells were scanty (5 10% of all cells). One hundred percent of the H. pylori-exposed rats showed persistence of chronic active ulcers (area, 1.76 to 19.63 mm2; mean, 8.95 +/- 6.15 mm2). The ulcer beds were infiltrated by acute and chronic inflammatory cells, abundant fibroblasts, and capillary networks. The raised ulcer borders were characterized by dilated glands lined by mature surface epithelial cells. Various special stains demonstrated the presence of H. pylori in the surface mucus and within the crypts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748216 TI - Distinctive infrared spectral features in liver tumor tissues of mice: evidence of structural modifications at the molecular level. AB - Mice were treated with griseofulvin (GF) containing diet or control diet for 12 months. The livers from mice fed griseofulvin showed large tumors that were excised and used for analysis. The infrared spectra from control liver tissue and tumor tissue from GF livers were measured and compared as a function of pressure up to 27 kbar. Many changes in the infrared spectral features of the tumor tissue were observed. Results showed that neoplasm formation involved structural modifications of nucleic acids, lipids, carbohydrates, and proteins in the liver cells, which were detected from the abnormal vibrations of the functional groups in these biomolecules. The amount of glycogen was dramatically decreased in the tumor tissue compared to the control tissue. Important changes in the strength of hydrogen-bondings in the phosphodiester backbone of the nucleic acids and in the C-O groups of tissue proteins and carbohydrates were observed. Stronger interchain interactions and thus close interchain packing among the lipids in the GF liver were evident. These results showed very close similarities with those obtained with other types of tumors such as human colon cancer, suggesting that a common pattern of molecular changes has been identified in neoplastic transformation. PMID- 1748217 TI - Effect of dietary n-3 fatty acids on atherosclerosis prone JCR:LA-corpulent rats. AB - Corpulent male rats of the atherosclerosis prone JCR:LA-corpulent strain were fed diets supplemented with 10% by weight of olive oil or red fish oil. These rats are obese, with VLDL hyperlipidemia and marked insulin resistance. The diets were maintained to 9 months of age. Olive oil-fed rats had a 45% reduction in triglyceride concentrations with no significant changes in cholesterol or phospholipids. Red fish oil caused significant reduction in all lipid classes, with a 65% reduction in triglycerides and 35% reduction in cholesterol concentrations. Olive oil caused increases in the relative concentrations of oleic acid-containing triglycerides, while red fish oil preferentially enriched the longer chain fatty acids. There were no significant changes in insulin or glucose metabolism. The incidence of myocardial lesions, characteristic of the JCR:LA-cp strain, was unaltered by either oil-supplemented diet. These results, in a spontaneous animal model for cardiovascular disease, are consistent with other studies showing that diets rich in n-3 fatty acids do not, in themselves, confer protection against cardiovascular disease in animal models with genetically or experimentally induced lipid disorders. PMID- 1748218 TI - Classification of perinatal deaths. PMID- 1748219 TI - Perinatal mortality in Norway: experience with perinatal audit. AB - In order to improve perinatal service, special committees have been established in every county in Norway. These committees are responsible for making local guidelines and performing inquiries (audits) of all perinatal deaths. The focusing upon avoidable and possibly avoidable factors and identification of suboptimal care seems to be valuable in improving the quality of medical work. In 1989 the perinatal mortality was 7.8 per 1000 births. PMID- 1748220 TI - Perinatal mortality related to low birth weight. PMID- 1748221 TI - Perinatal mortality in the East Flanders Prospective Twin Survey (preliminary results). PMID- 1748222 TI - Follow-up and hormone replacement in gynecological cancer patients. PMID- 1748223 TI - Progestogens in reproductive endocrinology. PMID- 1748224 TI - Subspecialization in gynecology and obstetrics: advantages and disadvantages. AB - To discuss the problem of subspecialization in our discipline is presently very popular. Whether or not a complete separation into the three subdisciplines: (1) materno-fetal medicine - obstetrics (2) surgical gynecology - gynecologic oncology (3) gynecologic endocrinology - reproductive medicine is recommended remains unclear in most of the statements. Some describe forms of only a supplementary postgraduate education, a kind of prolongation of the basic gynecologic and obstetrical training concentrated on one of the three main fields. The complete separation, i.e., in obstetrical medicine, reproductive medicine, gynecologic pelvic surgery, has the advantage of a more effective concentration on each of the respective subdisciplines in clinical work and in research. On the other hand, the separation will certainly produce several disadvantages: (a) What is inbetween the subdisciplines will be difficult to integrate. (b) The principle of the gynecologist functioning as a primary health care physician for women will be weakened, i.e., his competence for family planning, pregnancy and delivery of normal cases, for cancer screening of genital and breast tumors, for disorders of the cycle, for pelvic inflammatory diseases and for the care of postmenopausal women will be less integral. (c) The lectures will be more than at present split or overloaded with detailed facts. (d) The need of general gynecologic care - as well cost-effective as widely available - will less frequently be met than now. (e) The opportunities for younger colleagues to settle with an office of their own will be restricted. The disadvantages outweigh the advantages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748225 TI - Undergraduate education and recruitment in obstetrics and gynaecology. AB - The extent and quality of exposure to obstetrics and gynaecology that is required in the undergraduate curriculum has bearing on the knowledge, clinical skills and behaviour that are expected from the student. How much involvement should clinical obstetricians and gynaecologists have in teaching human reproduction and basic physiology and related science to the undergraduate? Who should teach sexual medicine? What is the extent of practical experience which students should have? Should the student have an opportunity to study a particular area in the discipline at depth in order to encourage interest and involvement and thereby facilitate recruitment? These issues are being addressed in curricular changes in Manchester, and option teaching is considered to have the potential of enhancing interest in obstetrics and gynaecology as a definitive career. PMID- 1748226 TI - Ovarian cancer: introduction and development in the treatment. PMID- 1748227 TI - Detection and localization of ovarian cancer with radiolabeled monoclonal antibodies. PMID- 1748228 TI - Treatment with biologic response modifiers in patients with ovarian cancer. AB - The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN gamma augmented natural killer activity in 2 of 3 patients. PMID- 1748229 TI - Prevention of perinatal consequences of pre-eclampsia with low-dose aspirin: results of the epreda trial. The Epreda Trial Study Group. AB - A multicentric randomized double-blind trial was realized in order to determine whether a treatment with a low-dose aspirin (150 mg/day) with or without dipyridamole (225 mg/day) was able to prevent the perinatal consequences of pre eclampsia. This study demonstrated a significant difference in birthweight and incidence of fetal growth retardation between treatment and placebo groups. No difference was demonstrated between aspirin and aspirin + dipyridamole patients. PMID- 1748230 TI - The role of lipids in nutrition during the first months of life. AB - The most important functional components of dietary lipids (triglycerides, cholesterol esters and phospholipids) are fundamental to normal growth and development of infants. Fatty acids are classified according to their chain length and their degree of saturation. Each class of fatty acid is involved in specific metabolic reactions: short-chain fatty acids act as local growth factors in the colon; medium- and saturated long-chain fatty acids are a good source of energy; polysaturated long-chain fatty acids are involved in metabolic regulation; and very long-chain fatty acids are important structural components of membranes. The development of the central nervous system depends on the amount and the quality of the lipid supply in the last months of prenatal and the first months of postnatal life. Placental cord blood during foetal life and breast milk provide fatty acids in the correct amounts and ratios. Fats in breast milk provide half the infant's calorific needs and maternal dietary habits can influence the lipid composition of milk. The preparation of blends of fats for formulas is under investigation in order to improve the lipid quality and to make formulas more similar to breast milk. A major goal of current research is to define the nutritional and metabolic relationships between fatty acid groups and between fats and the other dietary sources of calories in order to improve the composition of infant formulas, in particular for premature babies. PMID- 1748231 TI - Thyroid function and release of thyroid-stimulating hormone and prolactin from the pituitary in human obesity. AB - Thyroid function, basal serum thyroid-stimulating hormone (TSH) and prolactin concentrations, and the effects of 200 micrograms TSH-releasing hormone (TRH) given intravenously on TSH (delta TSH) and prolactin (delta prolactin) were investigated in 25 euthyroid obese subjects and 20 lean controls. No significant differences in serum thyroid hormone concentrations, glucose metabolism parameters, or basal TSH and prolactin concentrations were detected between groups, but a significant (P less than 0.01) increase in delta TSH and a significant (P less than 0.01) decrease in delta prolactin were observed in obese subjects. No significant differences in basal TSH and prolactin were observed in obese men and women compared with corresponding lean controls, but delta prolactin decreased significantly (P less than 0.01) in obese men and women compared with lean controls and TSH increased significantly (P less than 0.01) in obese men and women. No correlation was found between delta TSH or delta prolactin and body mass index. The study suggests that hyper-responsiveness of TSH and hyporesponsiveness of prolactin to TRH in obese subjects can be related to changes in the central serotoninergic system. PMID- 1748232 TI - Memory storage and effect of repeated treatment with a new antidepressant drug: rubidium chloride. AB - Following 15 days' treatment with saline, 48 mg/kg rubidium chloride, 5 mg/kg imipramine hydrochloride, 10 mg/kg sodium phenobarbitone, 1000 mg/kg piracetam, or 0.20 mg/kg strychnine nitrate all administered intraperitoneally, mice were evaluated by habituation of exploratory activity using an open-field apparatus. In control animals a significant (P less than 0.05) decrease in open-field responses (ambulation, rearing and defaecation) was seen following a 1-day intersession interval and there was no retention of exploratory activity after a 5-day intersession interval. Administration of imipramine or phenobarbitone for 15 days was found to impair retention of memory after 1 day, whereas treatment with rubidium chloride, piracetam, or strychnine for 15 days improve retention after a 5-day intersession interval. PMID- 1748233 TI - Indole-3-pyruvic acid as a possible hypnotic agent in insomniac subjects. AB - In a single-blind study six male patients (mean age 39.5 years) with moderate insomnia were treated with placebo for three nights, 100 mg indole-3-pyruvic acid (IPA) for three nights, 200 mg IPA for three nights, 100 mg IPA for two nights and placebo for two nights. Polygraphic recordings were made and total sleep time, sleep efficiency, sleep latency, slow wave sleep latency, rapid eye movement (REM) sleep latency, number of arousals (greater than 1 min), percentage and duration of wakefulness after sleep onset, percentage and duration of wakefulness after sleep onset, percentage and duration of sleep stages 1, 2, 3, 4 and REM were recorded. At the end of 13 days, total sleep time, duration of stage 2 sleep and total non-REM were significantly increased when compared with baseline. Total sleep time and duration of stage 2 and total non-REM sleep on completion were significantly decreased when compared with after 200 mg IPA (night 9). Results suggest an action of IPA on human sleep similar to that of exogenous melatonin and L-tryptophan, thus confirming that IPA could be used to increase serotonin and melatonin turnover. PMID- 1748234 TI - Acute effects of alcohol ingestion on the human serum concentrations of calcium and magnesium. AB - Alcohol has been shown to reduce serum calcium concentrations in several animal studies. In humans, using relatively low doses of alcohol, however, the results were inconclusive. In addition, the effect of alcohol consumption on serum magnesium concentrations is controversial. To elucidate the influence of alcohol ingestion on serum calcium and magnesium in humans 43 intoxicated patients and seven healthy volunteers who had not previously ingested alcohol were studied. There was an inversely related diminuition of serum calcium and magnesium concentrations with increasing serum alcohol. These effects of alcohol may play a role in the metabolic and clinical disorders observed in severely intoxicated people. PMID- 1748235 TI - Antiplatelet agents and their effect on complications during or soon after percutaneous transluminal coronary angioplasty. AB - In a retrospective study, during which 179 patients had undergone percutaneous transluminal coronary angioplasty (PTCA), the overall initial success rate fell suddenly and unexpectedly from more than 90% to 70.4%: 54.9% in patients not receiving antiplatelet therapy and 86.4% in patients treated orally with 300 mg triflusal three times daily or 300 mg acetylsalicylic acid plus 75 mg dipyridamole three times daily. The initial success rate was similar in patients with unstable (66.0%) and stable (77.6%) angina. The overall incidence of severe complications (mainly occlusion) was 16.2% and was significantly (P less than 0.01) greater in the patients not receiving antiplatelet therapy (23.1% versus 9.1%). There was no significant difference between incidence according to antiplatelet therapy used. It is concluded that antiplatelet therapy during the peri-angioplasty period (from 2 days before to 2 days after) may prevent periprocedural events in patients undergoing PTCA. PMID- 1748236 TI - Acute hypertension after renal allograft rejection therapy with OKT3 monoclonal antibody. AB - Acute rejection of renal allografts was treated with the monoclonal antibody OKT3 given intravenously. A variety of adverse events were observed on days 1 and 2 following treatment with 5 mg/day OKT3 for 10 days including heart failure, pulmonary oedema and hypertension. Continuous monitoring of 19 patients treated with OKT3 for acute renal allograft rejection detected a transient increase, lasting 2 h, in systolic and diastolic blood pressures on day 1. A larger increase in systolic and diastolic pressures lasting 11-13 h was observed on day 2. Treatment with 5 mg OKT3 on day 3 did not significantly increase systolic or diastolic pressure. It is concluded that OKT3 can aggravate hypertension and hypertensive emergencies may be encountered during the initial phase of OKT3 treatment. PMID- 1748237 TI - 1990 overview of GDM. Accomplishments of the last decade--challenges for the future. PMID- 1748238 TI - Metabolic alterations in adulthood after intrauterine development in mothers with mild diabetes. AB - We studied the long-term effects of maternal diabetes mellitus on the offspring of experimentally induced diabetic Wistar rats. When stressed by an intravenous glucose load, the adult female offspring had impaired glucose tolerance and developed gestational diabetes mellitus when pregnant. Our results show that even mild diabetes mellitus induces an abnormal intrauterine milieu that causes morphological and functional changes in fetal development with consequences for later life. PMID- 1748239 TI - Islet function in offspring of mothers on low-protein diet during gestation. AB - A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood. PMID- 1748240 TI - Long-term prospective evaluation of offspring of diabetic mothers. AB - We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis. PMID- 1748241 TI - Abnormal glucose tolerance during pregnancy in Pima Indian women. Long-term effects on offspring. AB - The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima Indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 162). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation. PMID- 1748242 TI - Diabetes mellitus after GDM. AB - The impact of factors that influence diabetes mellitus (DM) and impaired glucose tolerance (IGT) incidence rates among former gestation diabetes mellitus (GDM) patients undermine attempts at interstudy comparisons. The recommended diagnostic standards for GDM by oral glucose tolerance test (OGTT) are the O'Sullivan and Mahan criteria and the World Health Organization (WHO) criteria for IGT, which result in prevalence rates of 2.5 and 7.2%, respectively, when applied to 752 unselected pregnant women. In applying the O'Sullivan and Mahan criteria, the current open-ended definition of GDM without rules either to exclude overt diabetes uncovered by pregnancy or to require a return to a normal OGTT after pregnancy is shown to be a major source of differences in subsequent incidence rates of diabetes. For subsequent nonpregnant diagnoses, the differences between WHO and National Diabetes Data Group criteria and the allowable modifications within each of the diagnostic standards all result in different incidence rates of diabetes. Review of 12 worldwide studies of diabetes among former GDM patients indicated a wide range of incidence rates, from 19 to 87% for combined DM and IGT and 6 to 62% for DM. In applying WHO DM criteria to GDM patients and control subjects, the excess risk of diabetes among GDM patients was 18% in Copenhagen and 30.9% in Boston, MA. The potential impact of varying observation periods within studies was seen when the application of an actuarial method added a further 50% to the Boston incidence rates of both GDM patients and control subjects. Although the variability in diabetes incidence rates is wide, there is broad general agreement on the predictive nature of gestational blood glucose levels. PMID- 1748243 TI - Follow-up of women with previous GDM. Insulin, C-peptide, and proinsulin responses to oral glucose load. AB - Gestational diabetes mellitus (GDM) is a strong predictor of glucose intolerance later in life. Former GDM (n = 145) and control (n = 41) subjects were studied 3 4 yr after the index pregnancy. They were subjected to a 75-g oral glucose tolerance test (OGTT) with measurements of insulin, C-peptide, and proinsulin in the basal state and every 30 min for 180 min. In the former GDM group, 5 subjects (3.4%) had developed non-insulin-dependent diabetes mellitus (NIDDM), and 32 (22%) had developed impaired glucose tolerance (IGT; by World Health Organization criteria). In the control group, 2 (4%) had IGT. In the GDM group, IGT or NIDDM was significantly associated with obesity (body mass index [BMI] greater than or equal to 25 kg/m2) and earlier diagnosis of GDM during pregnancy (P less than 0.001). Nonobese (BMI less than 25 kg/m2) GDM subjects with normal glucose tolerance at follow-up had significantly higher mean glucose (P less than 0.01), insulin (P less than 0.05), and proinsulin (P less than 0.001) values during the OGTT than control subjects, whereas there was no significant difference in C peptide values. A comparison between control subjects with normal OGTT and BMI less than 25 kg/m2 (n = 39) and GDM subjects (n = 39) selected to have a comparable area under the glucose curve, BMI, and age demonstrated no group differences in glucose, C-peptide, or insulin levels, whereas the proinsulin levels were significantly higher (P less than 0.001) during the glucose load. The molar ratio between proinsulin and insulin was also significantly higher among the former GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748244 TI - Diagnosis of gestational diabetes. What are our objectives? AB - International agreement is lacking with regard to diagnostic criteria for gestational diabetes and its treatment. Consensus is not possible without agreement on the objectives in making the diagnosis. The most commonly used criteria in North America were validated by their predictive value for the subsequent development of overt diabetes in the years after affected pregnancies. The diagnosis is also deemed by many to be important as a risk factor for adverse perinatal outcome in the present pregnancy. Attempts have been made, in various parts of the world, to derive diagnostic criteria based on pregnancy outcome; unfortunately, these have not been so intensively studied as the standards cited above. There is also a lack of agreement on whether gestational diabetes should be considered a disease or merely a risk factor. In addition, consensus has not been reached on whether population-specific criteria should be used in each location or universally accepted diagnostic thresholds should be applied. Many philosophical questions remain unanswered, and numerous opportunities for investigation present themselves. Many of these are dealt with in this workshop conference, whereas others remain as goals to be attained. PMID- 1748245 TI - Serum lipids within 36 mo of delivery in women with recent gestational diabetes. AB - We prospectively evaluated fasting serum total cholesterol (chol), low- and high density lipoprotein cholesterol (LDL-chol and HDL-chol), and triglycerides (TGs) in a large cohort of Hispanic women during the first 36 mo after pregnancies complicated by gestational diabetes mellitus (GDM). In 1340 women studied 6-12 wk postpartum (PP-GDM group), chol and LDL-chol were similar to levels in 43 postpartum control subjects without prior GDM. Compared with control subjects (2.01 +/- 1.24 mM), TG was elevated in the PP-GDM women with diabetes mellitus (DM) (2.86 +/- 2.21 mM, P less than 10(-5)) and impaired glucose tolerance (IGT) (2.64 +/- 1.68 mM, P = 0.02) but not in those with normal glucose tolerance (2.00 +/- 1.21 mM). HDL-chol was decreased in PP-GDM women with DM compared with those with normal glucose tolerance. A subgroup of 157 women with prior GDM returned for at least one annual follow-up test on nonhormonal contraception (FU-GDM: n = 60 at 3-11 mo after delivery, n = 78 at 12-23 mo, and n = 39 at 24-35 mo). The cumulative prevalence of DM by 36 mo was 40%. Chol or LDL-chol levels did not significantly change during the 1-yr intervals in the FU-GDM group and were similar to a control group of 36 women without prior GDM. TG was elevated and HDL chol was decreased in the FU-GDM women with DM at 3-11 mo but not thereafter. Overall, the prevalence of moderate- and high-risk LDL-chol in the FU-GDM group was not different from that of control subjects. These findings suggest that lipid abnormalities are uncommon during the first 36 mo after delivery in women with recent GDM. The abnormalities found consisted of increased TG and decreased HDL-chol in subjects who had developed DM during the study period. PMID- 1748246 TI - Preconception counseling and contraception after gestational diabetes. AB - Women with gestational diabetes mellitus (GDM) diagnosed in the period 1978-1984 were followed for on average 6 yr after the index pregnancy. Thirty percent had diabetes mellitus at the follow-up examination, and preliminary results indicate that at least another third will develop diabetes during a subsequent pregnancy. Therefore, family planning and contraceptive guidance should follow the lines for women with pregestational diabetes. When low-dose hormonal contraceptives containing ethinyl estradiol and levonorgestrel were given to women with previous GDM, glucose tolerance and lipoprotein levels remained unchanged during a 6-mo treatment. However, insulin response to oral glucose increased significantly after hormonal intake for 6 mo. A triphasic preparation resulted in a significantly lower insulin response than a low-dose monophasic preparation. However, the results indicate that low-dose oral-contraceptive compounds appear to be safe for women with previous GDM when administered for limited periods. At the follow-up examination, we found no increased risk of developing diabetes in women with previous GDM who used oral contraception. We consider the intrauterine contraceptives (IUD) a safe and effective alternative for women with previous GDM. Of 154 women with GDM, 33% chose IUD, 22% a combination-type oral contraceptive, and 16% barrier methods as their first choice of contraception 2 mo postpartum. We conclude that family planning and qualified contraceptive advice are important in women with previous GDM. PMID- 1748247 TI - New National Academy of Sciences guidelines for nutrition during pregnancy. PMID- 1748248 TI - Energy requirements of pregnancy. AB - The energy requirements of pregnancy is a topic of considerable uncertainty because the apparent energy costs--to supply the energy required for the changes in maternal and fetal tissues and to cover the increase in basal metabolic rate (BMR), amounting to the equivalent of an extra 250-300 kcal/day--are rarely paralleled by actual findings. However, few studies have investigated this problem in a controlled longitudinal and statistically acceptable fashion. In this study, measurements of energy intake, BMR, body weight and fatness, physical activity, and mechanical efficiency of movement were made on 162 women in Scotland at 2- to 4-wk intervals throughout pregnancy, and data from 98 of these women were also obtained in the prepregnant state. Data from a parallel study in the Netherlands are also given. The gains in body weight, fatness, the fetal and placental weights, and the increase in BMR were all at the normal expected values. However, increases in energy intake were on the order of only 100 kcal/day during the second and third trimesters. Comparatively small reductions in physical activity, which would be difficult to measure precisely, are described that could account for the difference between actual energy intake and the energy costs of pregnancy. PMID- 1748249 TI - Monitoring the severity of metabolic disturbances and effectiveness of management of gestational diabetes mellitus. AB - To monitor the severity of metabolic disturbances during gestational diabetes mellitus (GDM), some risk factors existing at the time of diagnosis must be considered, including age of the pregnant women, early gestational age at diagnosis, high fasting blood glucose level, high HbA1c or fructosamine levels, or high amniotic fluid insulin level. The degree of OGTT abnormality will also influence the therapeutic approach, although the insulin response to the glucose challenge seems to be of little discriminating value. Effectiveness of the treatment can be appreciated by self-monitoring of blood glucose, although the practical precision of these measures and their necessary repetitions will limit clear-cut evaluation of borderline cases. HbA1c and fructosamine are of little help because of lack of sensitivity and time delay between changes in blood glucose and associated glycosylated protein changes. Whether other parameters such as amino acids, growth factors, or related compounds are more specifically linked to the physiopathology of GDM complications remains to be established but would help in monitoring GDM metabolic disturbances in the future. Meanwhile, prophylactic insulin treatment may still constitute a pragmatic approach, taking into account possible and poorly appreciated drawbacks from overtreatment, e.g., maternal hyperinsulinism and chronic hypoglycemia. PMID- 1748250 TI - Calorie restriction for treatment of gestational diabetes. AB - Birth weights of infants of 35 gestational diabetic mothers treated with calorie restriction alone (1200-1800 kcal) were compared with those of infants of 2337 nondiabetic women, including two control groups (A and B) matched for race, body mass index, age, and parity. All women were screened for gestational diabetes with the O'Sullivan screening method, and a 3-h oral glucose tolerance test was performed on all abnormal results. Control group A mothers had a normal screen, and control group B mothers had an abnormal screen with a normal glucose tolerance test. Pregnancy weight gain was significantly less for the gestational diabetic mothers (mean +/- SD 4.6 +/- 4.9 kg) than for the general prenatal population (9.3 +/- 5.3 kg), group A control subjects (9.7 +/- 5.3 kg), and group B control subjects (9.7 +/- 5.4 kg; P less than 0.0005). No infant of a gestational diabetic mother was below the 10th percentile for weight, and birth weights were similar to those of the control groups even though weight gain after the 28th wk of gestation was only 1.7 +/- 1.6 kg. The frequency of macrosomia (birth weight greater than or equal to 4000 g) was similar among the gestational diabetic mothers (9.3%), the general prenatal population (7.4%), and group A mothers (11.6%) but significantly higher for the group B control subjects (20.9%; chi 2 = 8.57, P less than 0.005). This study demonstrated that gestational diabetic mothers who are calorie restricted have infants with normal birth weights and a frequency of macrosomia less than that of screen-positive nondiabetic women with similar macrosomic risk factors. PMID- 1748251 TI - Metabolic effects of hypocaloric diets in management of gestational diabetes. AB - Although hypocaloric diets have been advocated for the management of the obese gravida and the obese mother with gestational diabetes, there is no general agreement on how severely calories should be restricted or on how this therapeutic approach compares with insulin therapy. The lack of consensus is in part because of the lack of studies comparing insulin management with the effects of different degrees of hypocaloric feeding and its effects on metabolism and glycemic status. We review the effects of 50 and 33% calorie restriction on glycemic status and intermediary fuel status in obese gestational diabetic subjects and compare the results with the administration of 20 U NPH and 10 U regular insulin every morning, a therapy of proven value in reducing macrosomia in gestational diabetes. When the two calorie-restriction regimens were compared after a 9-h overnight fast, glycemic status improved 10-20% on both. Ketonuria increased about twofold with 50% calorie restriction, but on average no increase in ketonuria was seen on the 33% calorie-restriction regimen. Both calorie restriction programs led to a reduction in levels of plasma triglyceride, a correlate of infant birth weight. In contrast, the insulin regimen diminished ketonuria, but glycemic status improved little, and plasma triglyceride concentrations did not decline. Although more studies are needed to confirm these trends, the beneficial effect of 33% calorie restriction, which occurred without marked ketonuria, is consistent with previous studies in gestational diabetes. In addition, the simultaneous improvements observed in plasma glucose and triglyceride concentrations suggest that moderate calorie restriction may be valuable in preventing macrosomia in the offspring of the obese subject with gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748252 TI - Percentage of carbohydrate and glycemic response to breakfast, lunch, and dinner in women with gestational diabetes. AB - We studied the relationship between 1-h glucose response and the percentage of carbohydrates in a given meal in 14 gestational diabetic women who did not require insulin therapy and were between 32 and 36 wk gestation. Each subject was greater than 130% ideal body weight and was placed on a diet of 24 kcal.kg-1.24 h 1, with 12.5% of calories at breakfast and 28% of the calories at lunch and again at dinner, with other calorie intake divided among three snacks. Glycemic response was monitored by self-monitoring of blood glucose 1 h after the start of each meal. Ten postprandial values for each meal were averaged for each of the 14 women. The correlation between percentage of carbohydrates and postprandial glucose level at 1 h was strongest for dinner (r = 0.95, P less than 0.001), with more variability seen at breakfast (r = 0.75, P = 0.002) and lunch (r = 0.86, P = 0.001). To maintain a 1-h postprandial whole-blood glucose level less than 7.78 mM required the following percentages of carbohydrates in each meal: 45% at breakfast, 55% at lunch, and 50% at dinner. If 1-h postprandial whole-blood glucose level was to remain less than 6.67 mM, then the respective values were 33, 45, and 40%. We conclude that the glycemic response to a mixed meal in subjects with gestational diabetes is highly correlated with the percentage of carbohydrates of the ingested meal and varies among individuals and among breakfast, lunch, and dinner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748253 TI - Exercise in the treatment of NIDDM. Applications for GDM? AB - Physical training is associated with lower plasma insulin concentrations and increased sensitivity to insulin in skeletal muscle and adipose tissue of individuals with non-insulin-dependent diabetes mellitus (NIDDM). The benefits of exercise to individuals with NIDDM in terms of increased insulin sensitivity could be applied to reversing the insulin resistance associated with gestational diabetes mellitus (GDM). Exercise may also benefit women with GDM by acting as an adjunct to diet in preventing excessive weight gain and preventing or decreasing the severity of hypertension and/or hyperlipidemia during pregnancy. Regular physical exercise should be considered as a potential approach to the prevention and treatment of GDM. PMID- 1748254 TI - Is exercise safe or useful for gestational diabetic women? AB - The mainstay of management of the gestational diabetic woman is dietary manipulation to achieve and maintain normoglycemia. If normoglycemia cannot be sustained by diet alone, then insulin therapy is initiated. We instituted a series of studies to observe the value and safety of a cardiovascular fitness program to improve glucose tolerance in gestational diabetic women. We first evaluated the safety for pregnant women of five aerobic exercise machines by observing the effect of these different forms of exercise on uterine activity during the third trimester. We found that upper-extremity exercise produced no uterine contractions, but lower-extremity exercise tended to produce contractions. Upper-extremity exercise, in addition to dietary therapy, was then assigned to 10 gestational diabetic women who were matched for amount of glucose intolerance to 10 gestational diabetic women managed by diet alone. The mean fasting plasma glucose +/- SD after 6 wk was 4.87 +/- 0.34 mM in the diet group versus 3.89 +/- 0.37 mM in the diet-plus-exercise group. The mean postglucose challenge in the diet group was 10.40 +/- 0.16 mM versus 5.9 +/- 1.1 mM in the diet-plus-exercise group. Thus, upper-arm exercise may provide a useful treatment option for gestational diabetes and may obviate the need for insulin. PMID- 1748255 TI - Insulin secretion and insulin resistance in pregnancy and GDM. Implications for diagnosis and management. AB - Glucose tolerance deteriorates in human pregnancy, but approximately 97-98% of all pregnant women retain a normal glucose tolerance, and only 2-3% develop gestational diabetes mellitus (GDM). Both nondiabetic pregnant women and women with GDM exhibit much higher insulin responses to oral or intravenous administration of glucose or amino acids than found in the nonpregnant state, and the insulin responses to a protein-rich meal are also significantly enhanced in pregnancy. Both quantitative and qualitative differences in insulin secretion exist between pregnant women with normal glucose tolerance (NGT) and women with GDM. Insulin responses to oral glucose and protein-rich meals are thus lower in pregnant women with GDM than in women with NGT, despite significantly higher mean plasma glucose concentrations in the women with GDM. Furthermore, peak plasma insulin concentrations occur later in women with GDM than in pregnant control subjects. Finally, a reduced first-phase insulin response to intravenous glucose can be observed in some women with GDM. Impairment of glucose tolerance in pregnancy is not related to a disproportional secretion of proinsulin nor is increased insulin degradation involved. These observations point to pregnancy as a state of peripheral insulin resistance. Because insulin-receptor binding is only slightly changed in pregnancy and not significantly different in pregnant women with NGT and women with GDM, it follows that the insulin resistance is located at the postreceptor level. Insulin-clamp and "minimal model" studies have shown that the whole-body insulin sensitivity is similarly reduced by about two thirds of nonpregnant values in pregnant women with NGT and women with GDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748256 TI - Exercise in gestational diabetes. An optional therapeutic approach? AB - Forty-one patients with gestational diabetes requiring insulin were enrolled in a randomized study to investigate the efficacy of an exercise program in normalizing glucose tolerance. Seventeen of 21 patients completed the exercise program while maintaining normoglycemia and obviating insulin therapy. Maternal and neonatal complications did not differ between the study and control groups. The type of program described appears to be safe and can serve as a model for exercise prescription for pregnant diabetic women to attain improved glucose tolerance. PMID- 1748257 TI - Rationale for insulin management in gestational diabetes mellitus. AB - A prospective study was undertaken to test the hypothesis that insulin treatment in patients with gestational diabetes mellitus (GDM) with fasting plasma glucose (FPG) greater than 5.3 mM significantly reduces adverse perinatal outcome. Assigned to insulin or diet treatment based on FPG were 471 GDM women. Four factors believed to be associated with infants large for gestational age (LGA) were evaluated: FPG, overall glycemic control, maternal weight, and treatment regimen. We found that when glycemic control was optimized, the key factors related to large infants were FPG and treatment modality. In the low-FPG group (less than 5.3 mM), diet therapy achieved an incidence of 5.3% LGA. When insulin therapy was used to optimize control, an incidence of 3.5% LGA was found. Patients in the mid-FPG group (5.3-5.8 mM) had a higher increased rate of LGA (28.6%) for diet-treated versus insulin-treated women (10.3%). In addition, a fourfold increased risk for LGA was found in the diet-treated obese subjects in the mid-FPG group compared with insulin-treated obese women. Finally, treatment with insulin resulted in similar incidence of LGA within all FPG groups. We concluded that FPG greater than 5.3 mM can be the basis for initiation of insulin treatment in GDM subjects with optimization of glycemic control as the goal. This approach may contribute significantly to reduced neonatal risk and may foster a standardized method for rapid and effective assignment to treatment. PMID- 1748258 TI - Gestational diabetes mellitus. Levels of glycemia as management goals. AB - In the United States, glucose tolerance test criteria for the diagnosis of gestational diabetes mellitus are, in plasma glucose after a 100-g challenge, as follows: fasting, greater than 5.8 mM; 1 h, greater than 10.6 mM; 2 h, greater than 9.2 mM; and 3 h, greater than 8.1 mM; any two values must be elevated. The Second International Workshop-Conference on Gestational Diabetes Mellitus recommended in 1985 that, once diagnosed, women should receive dietary therapy. If fasting or 2-h postprandial hyperglycemia later occurs (fasting, greater than 5.8 mM; 2-h, greater than 6.7 mM), insulin therapy should begin. Data from others have suggested both that the criteria for diagnosis may be too liberal and that the thresholds for instituting insulin therapy may be too high. We address these two issues by reviewing several papers with conflicting conclusions. There is controversy over whether women with gestational diabetes diagnosed by glucose tolerance testing, but who have fasting plasma glucose levels less than 5.8 mM and 2-h postprandial values less than 6.7 mM, should also be insulin treated. Finally, the usual clinical criteria for making therapeutic decisions all rely on glycemia. Other fuels (amino acids, lipids, and ketones) are regulated by circulating insulin and have deleterious effects on fetal development. Further study is required to make more sound clinical decisions based not just on glycemia but on the entire metabolic milieu. PMID- 1748259 TI - Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. PMID- 1748260 TI - Gestational diabetes mellitus. Influence of race on disease prevalence and perinatal outcome in a U.S. population. AB - We explore whether racial differences in a United States population influence disease prevalence and perinatal outcome in gestational diabetes mellitus (GDM). The data presented are based on 3744 consecutive patients who underwent universal screening at 24-28 wk gestation; those with a 1-h plasma glucose greater than or equal to 7.2 mM underwent a 100-g 3-h oral glucose tolerance test (OGTT). The overall prevalence of GDM was 3.5 cases/100 with the standard O'Sullivan-Mahan diagnostic criteria derived for plasma, whereas use of the Carpenter-Coustan modification of the O'Sullivan-Mahan criteria yielded a prevalence of 5.5. The population was 39.1% white, 37.7% black, 19.8% Hispanic, and 3.4% Oriental/other. For those patients with a nondiagnostic test, mean plasma glucose at each time point of the OGTT was similar for all racial groups. Because of demographic and phenotypic heterogeneity between different racial groups, the influence of these different variables on the prevalence of GDM was tested by multiple logistic regression. Black and Hispanic race, maternal age, and percentage ideal body weight were found to have significant independent effects on the prevalence of GDM (P less than 0.05, 0.001, 0.001, and 0.001, respectively). The adjusted relative risk of GDM was significantly higher in black (1.81, 95% confidence interval [CI] 1.13-2.89, P less than 0.05) and Hispanic (2.45, 95% CI 1.48-4.04, P less than 0.001) patients compared with whites. The influence of race on infant birth weight was examined in the 92 patients with GDM controlled with diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748261 TI - Gestational diabetes. Can epidemiology help? AB - Diagnostic criteria for diabetes mellitus (DM) and impaired glucose tolerance from oral glucose tolerance test results in adults are reviewed in the epidemiological context, highlighting the residual differences between World Health Organization (WHO) and National Diabetes Data Group (NDDG) glycemic criteria with respect to the diagnosis of gestational diabetes. Although the value of the diagnosis of DM (WHO/NDDG criteria) in pregnancy is not called into question, attention is drawn to the paucity of evidence linking lesser degrees of glucose intolerance with significant disturbance of pregnancy outcome when confounding variables such as maternal age, adiposity, and parity are allowed for. It is in the area of the detection and treatment of these lesser degrees of glucose intolerance in pregnancy that serious questions of the detriment-to benefit ratio arise. A population-based multiethnic multicultural inquiry into diagnostic methodology and criteria in pregnancy is proposed, jointly sponsored by the WHO and the International Diabetes Federation, extending, if possible, to a controlled clinical trial of the effects of intervention. PMID- 1748262 TI - Comparison of diagnostic criteria of IGT, borderline, and GDM. Blood glucose curve and IRI response. AB - A 75-g oral glucose tolerance test (OGTT) was performed in 615 nonobese pregnant women (mean +/- SD age 29.7 +/- 4.3 yr) who were referred to the Division of Internal Medicine at our diabetes center because of glycosuria. Seventy-seven cases were found to have urinary glucose at the first trimester, 185 at the second trimester, and 353 at the third trimester. With their 75-g OGTT results, the diagnostic criteria of borderline (formulated by the Japan Diabetes Society), impaired glucose tolerance (IGT; defined by the World Health Organization [WHO]), and gestational diabetes mellitus (GDM; determined by the Japan Society of Obstetrics & Gynecology standards) were compared through blood glucose (BG) curves and immunoreactive insulin (IRI) responses. Borderline (fasting BG greater than or equal to 6.1 and less than 7.8 mM and 2-h BG greater than or equal to 6.7 and less than 11.1 mM) is neither diabetes nor normal. IGT is as referred to by the WHO. GDM exceeds two points of fasting BG greater than or equal to 5.6 mM, 1 h BG greater than or equal to 10.0 mM, or 2-h BG greater than or equal to 8.3 mM. Diabetes mellitus (DM) is as referred to by the Japan Diabetes Society (same as the WHO). The prevalence of abnormal glucose tolerance among all 615 pregnant women was 54.6% in borderline, 24.5% in IGT, 7.3% in GDM, and 3.4% in DM. The 2-h BG levels in IGT during the first trimester were higher than in borderline (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748263 TI - Incidence and severity of gestational diabetes mellitus according to country of birth in women living in Australia. AB - Gestational diabetes mellitus (GDM) was diagnosed in 1928 of 35,253 (5.5%) tested pregnancies at the Mercy Maternity Hospital in Melbourne between 1979 and the end of 1988. Compared with women born in Australia and New Zealand, the incidence of GDM was significantly greater in women born on the Indian subcontinent (15%); in women born in Africa (9.4%), Vietnam (7.3%), Mediterranean countries (7.3%), and Egypt and Arabic countries (7.2%); and in Chinese (13.9%) and other Asian (10.9%) women. There was no significant difference for women born in the United Kingdom and northern Europe (5.2%), Oceania (5.7%), North America (4.0%), or South America (2.2%). With the World Health Organization criteria as a guide to the severity of hyperglycemia, compared with mothers born in Australia and New Zealand, there were significant increases in the incidences of the more severe grades of GDM in parturients born in the Mediterranean region, Asia, the Indian subcontinent, Egypt, and Arabic countries. The incidence of GDM increased significantly in all racial groups, rising from 3.3% during 1979-1983 to 7.5% during 1984-1988. PMID- 1748264 TI - Insulin sensitivity in pregnancy. AB - Quantitation of insulin sensitivity (SI) with the insulin suppression test, glucose clamp, or the minimal model method has been achieved in various clinical circumstances. The application of these techniques to pregnancy has been limited. It is important to utilize sensitive and reproducible methods to study SI changes in pregnancy to fully understand the normal and pathological metabolic alterations that occur during gestation. These techniques demonstrate that various factors (obesity, body fat distribution, age, dietary manipulation, and exercise) may affect SI measures. The various pregnancy hormones have differential effects on insulin action. There is consensus among the limited in vivo studies in human pregnancy that late gestation is associated with significantly impaired SI compared with the nonpregnant state. Studies with appropriate matching between control and gestational diabetic subjects have failed to demonstrate a significant difference in SI between groups in the third trimester. PMID- 1748265 TI - The placenta. Not just a conduit for maternal fuels. AB - The placenta is a specialized organ of exchange that provides nutrients to and excretes waste products from the fetus. The exchange of nutrients between placenta and fetus involves three major mechanisms: 1) direct transfer of nutrients from the maternal to the fetal plasma, 2) placental consumption of nutrients, and 3) placental conversion of nutrients to alternate substrate forms. Although direct transfer has been considered the primary means by which placental fetal exchange controls the supply of nutrients to the fetus and thereby fetal metabolism and growth, the considerable metabolic activity of the placenta provides a large and fundamentally important contribution to both the quality and quantity of nutrient substrates supplied to the fetus; e.g., placental O2 and glucose consumption rates approach or even exceed those of brain and tumor tissue. Other placental metabolic activities include glycolysis, gluconeogenesis, glycogenesis, oxidation, protein synthesis, amino acid interconversion, triglyceride synthesis, and chain lengthening or shortening of individual fatty acids. Thus, consideration of the metabolism of the placenta is essential for a more complete understanding of how the placenta regulates nutrient transfer to the fetus, fetal energy balance, and fetal growth. PMID- 1748266 TI - Altered diastolic function in asymptomatic infants of mothers with gestational diabetes. AB - Left and right ventricular filling was studied prospectively in 50 full-term (39.4 +/- 1.3 wk) asymptomatic newborns of mothers with gestational diabetes mellitus (GDM). Their data were compared with those of 80 asymptomatic full-term (39.8 +/- 1.2 wk) infants who served as control subjects. Infants were examined in the immediate newborn period (less than 48 h) and then again at 2-4 and 6-9 wk. Although mean weight, length, and gestational age did not differ, the mean +/ SD left ventricular dimensions during diastole (1.73 +/- 0.15 vs. 1.81 +/- 0.18 cm, P = 0.007) and systole (1.22 +/- 0.15 vs. 1.31 +/- 0.17 cm, P = 0.004) were significantly lower in infants of mothers with GDM compared with control infants. Diastolic measurements suggested a shift from the early diastolic filling of the ventricle to the later period of atrial systole in infants of mothers with GDM. A lower initial one-third area fraction and a higher peak flow velocity and velocity time integral during atrial systole were noted at the mitral valve in infants of mothers with GDM. These changes had resolved by 2-4 wk of age. The altered diastolic filling patterns in infants of mothers with GDM indicate poor myocardial relaxation and/or decreased passive compliance of the ventricular myocardium. These alterations were observed in asymptomatic infants in the absence of left ventricular or septal hypertrophy. If exposed to significant stress such as asphyxia or sepsis, the observed myocardial dysfunction could lead to higher morbidity in these infants. PMID- 1748267 TI - Impact of maternal fuels and nutritional state on fetal growth. AB - Several maternal plasma fuel abnormalities have been described in gestational diabetes mellitus (GDM), and all may contribute to the development of fetal macrosomia, generally because of the surfeit of calories they provide. Elevated maternal plasma glucose and amino acid concentrations represent key disturbances, because they are also well-known fetal pancreatic beta-cell secretagogues. Fetal hyperinsulinemia contributes to macrosomia in a special way by selectively accelerating fuel utilization and storage in insulin-sensitive fetal tissues. Maternal obesity intensifies the insulin resistance already present in late pregnancy and probably exaggerates the metabolic abnormalities attending GDM that impact on fetal growth and development. However, the means by which maternal obesity per se promotes the development of heavy babies in nondiabetic pregnancies remains poorly defined. Significant correlations exist between newborn birth weight and the levels of maternal plasma glucose, amino acids, free fatty acids, and triglycerides in diabetic pregnancies. However, the relative influence of each disturbance on fetal birth weight remains controversial and requires more detailed investigation. PMID- 1748268 TI - Sonographic measurement of fetal humeral soft tissue thickness in pregnancy complicated by GDM. AB - Sonographic measurement of fetal humeral soft tissue thickness (STT) was performed in 93 women with gestational diabetes mellitus during the third trimester. STT measurements revealed accelerated growth in large for gestational age infants at 31 wk gestation. This new measurement proved to be the most accurate predictor of excessive fetal size compared with other standard ultrasound parameters (sensitivity 82%, specificity 95%, positive predictive value 90%). Asymmetrical growth was more evident in infants with large STT measurements in utero. Humeral STT measurement may distinguish large fetuses with truncal obesity from those that are symmetrically large, thereby allowing prediction of risk for birth trauma before delivery. PMID- 1748269 TI - Neonatal hypoglycemia. Back to basics in diagnosis and treatment. AB - Hypoglycemia continues to be found in infants of diabetic mothers, although the significance of the observation remains to be defined in terms of long-term neuro development and behavior. Most follow-up studies no longer identify CNS problems. The criterion, i.e., the level of blood glucose at which the diagnosis should be made, has evolved and drifted toward the adult level. No single criterion can be used dependably to make this clinical and chemical diagnosis. PMID- 1748270 TI - Gestational diabetes mellitus. A survey of perinatal complications in the 1980s. AB - Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, and major congenital anomalies (P less than 0.05). Although our GDM patients were stringently managed with diet or diet plus insulin, as indicated, and maintained almost euglycemic values, these neonatal complications could not be eliminated. Our data may be consistent with observations published during the last decade that even subtle degrees of maternal hyperglycemia can have a detrimental effect on perinatal outcome. Most neonatal complications readily respond to therapy if diagnosed and treated early and promptly. Macrosomia can have a detrimental effect on delivery (trauma) and later long-term implications during childhood. Tight metabolic control with diet and, when indicated, insulin treatment may be advantageous in reducing fetal birth weight. Criteria of how tight the metabolic control should be remain to be accurately defined. PMID- 1748271 TI - Obstetric complications with GDM. Effects of maternal weight. AB - Obstetric complications recorded prospectively were assessed retrospectively in 150 women with gestational diabetes mellitus (GDM) and 305 control subjects matched for age, parity, and ethnicity. Intensive diet therapy and self monitoring of capillary blood glucose were used to obtain postprandial euglycemia; 22% of GDM subjects required insulin. GDM and control subjects were grouped by body mass index to detect any influence of maternal prepregnancy weight on outcome. Polyhydramnios, preterm labor, and pyelonephritis were not more frequent in GDM, but hypertension without proteinuria (7.3 vs. 3.3%) and preeclampsia (8 vs. 3.9%) were more frequent in GDM. The frequency of hypertensive complications in GDM was not totally attributable to being overweight. Abnormalities of labor, birth trauma, and fetal macrosomia were not more common in GDM; 6.7% of the infants of mothers with GDM weighed greater than 4200 g at birth compared with 3.6% of control infants (NS), and 10% were large for gestational age and sex compared with 6.6% of control infants (NS). Despite this, cesarean delivery was more common in GDM (35.3 vs. 22%, P less than 0.01), mostly due to significantly more cesarean births without labor. PMID- 1748272 TI - Influence of pregnancy on the 75-g OGTT. A prospective multicenter study. The Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes. AB - This study reports the responses to a 75-g oral glucose tolerance test (OGTT) in 1009 pregnant women from throughout Europe. We reached the following conclusions. 1) A pregnant woman tends to have blood glucose concentrations that are elevated for a longer period of time after an oral glucose load. Therefore, approximately 10% of women will reach or exceed 8 mM glucose at 2 h, but it is unlikely that 10% of European women have disordered carbohydrate metabolism. 2) The fasting and 1-h values should be included in any analysis of the response of the patient. By doing this, many fewer women will have responses regarded as abnormal; in this series, it reduced the 79 women with a 2-h value greater than 8 mM to 15 who were considered to have carbohydrate intolerance (2 with diabetes, 13 with impaired glucose tolerance [IGT]). 3) By increasing the 2-h cutoff value to greater than or equal to 9 mM, the number of women regarded as at risk would be reduced by greater than 50% (from 79 to 32 in this series), but 10 of the 13 women with two abnormal values would still have been detected, as would the 2 diabetic women. 4) From the obstetric viewpoint, mothers who screen positive do not have bigger babies, they deliver close to term, and they do not have particular stigmas such as a family history of diabetes or an increased tendency to smoke or to have an adverse obstetric outcome. However, they do tend to be older and heavier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748273 TI - Intermediary metabolism in pregnancy. First theme of the Freinkel era. AB - During the first half of gestation in the rat, maternal net body weight increases rapidly, whereas in the second half of gestation, the mass of maternal structures declines, coincident with the rate of maternal fat accumulation. Enhanced maternal food intake, extrahepatic tissue lipoprotein lipase (LPL) activity, and adipose tissue lipogenesis are responsible for the progressive accumulation of maternal fat. However, during late gestation, decreased fat synthesis in maternal adipose tissue, enhanced lipolytic activity, and decreased LPL activity deplete maternal fat depots. These changes, plus enhanced endogenous production of triglyceride-rich lipoproteins, are also responsible for maternal hypertriglyceridemia. This condition benefits the offspring in two ways: 1) enhanced LPL activity in maternal liver when fasting increases triglyceride consumption for ketone body synthesis, giving the basis for accelerated starvation; and 2) induction of LPL activity in the mammary gland before parturition diverts maternal circulating triglycerides to milk synthesis in preparation for lactation. The magnitude of the maternal-fetal glucose transfer was higher than that of any of the other substrates studied, including alanine, and despite actions to spare glucose, this transfer causes maternal hypoglycemia, which is especially intense in the fasting condition. This increases sympathoadrenal activity in the mother, which may contribute to her active gluconeogenesis. Glycerol was a more efficient glucose precursor than alanine and pyruvate, and whereas glycerol placental transfer is very small, it is proposed that the fetus benefits from this product of adipose tissue lipolysis when it is previously converted into glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748274 TI - Functional maturation and proliferation of fetal pancreatic beta-cells. AB - We review some key aspects of the maturation of stimulus-secretion coupling and the regulation of DNA replication in the fetal beta-cell. During fetal life, the beta-cell shows a poor insulin response to glucose, although it responds to several other nonnutrient stimuli. However, chronic exposure to glucose in excess of basal levels can induce maturation of the stimulus-secretion coupling. Studies of glucose metabolism and the transmembrane flow of K+ and Ca2+ indicate that the attenuated glucose-stimulated insulin release is due to an immature glucose metabolism resulting in impaired regulation of ATP-sensitive K+ channels in the plasma membrane of the fetal beta-cell. In late fetal life, glucose is also a strong stimulus to beta-cell replication, and metabolism of glucose is a prerequisite for this process. Glucose stimulates proliferation by recruiting beta-cells from a resting state into a proliferative compartment composed of cells in an active cell cycle. The proliferative compartment comprises less than 10% of the total islet cell population even at maximal stimulation. The proliferation of fetal beta-cells is also regulated by several peptide growth factors such as growth hormone, insulinlike growth factor I, and platelet-derived growth factor. The observation that glucose can both induce precocious maturation of the stimulus-secretion coupling and stimulate proliferation of the fetal beta cell explains the intrauterine hyperinsulinemia and beta-cell hyperplasia of the offspring of diabetic mothers with relatively mild hyperglycemia. However, severe hyperglycemia, at least when induced in rats, seems to retard rather than stimulate beta-cell growth. PMID- 1748275 TI - Diabetic embryopathy. Studies with animal and in vitro models. AB - Diabetic pregnancy is associated with an increased risk for fetal maldevelopment for a largely unknown reason. A decade ago, Norbert Freinkel suggested that the altered fuel mixture offered to the growing conceptus may be the key to most of the changes in the embryogenesis of diabetic pregnancy. He coined the term fuel mediated teratogenesis. During early pregnancy, periods of maternal hyper- and hypoglycemia may cause marked changes in the availability of glucose to the conceptus. Also, increased concentrations of lipids, notably ketone bodies, and branched-chain amino acids in the maternal circulation contribute to a changed fuel mixture for the embryo. In a recent experimental study of diabetic rats, it was found that the maternal metabolism of all three major classes of nutrients and maternal somatic growth during gestation covaried with the development of the embryo. Consequently, the maintenance of normal concentrations of metabolites from all nutrient classes may be important for prevention of adverse fetal outcome in diabetic pregnancy. In vitro, a high glucose concentration causes embryonic dysmorphogenesis by generation of free oxygen radicals. An enhanced production of such radicals in embryonic tissues may be directly related to an increased risk of congenital malformations in diabetic pregnancy. Thus, the notion that alterations in the net transfer of cellular fuels from the diabetic mother to her offspring may cause embryonic dysmorphogenesis, which suggests that combustion of the fuel may produce compounds that impair embryonic development, has obtained experimental support. If this is also true for human diabetic pregnancy, it has therapeutic implications. PMID- 1748276 TI - Biphasic effects of maternal metabolism on fetal growth. Quintessential expression of fuel-mediated teratogenesis. AB - More than a decade ago, Norbert Freinkel postulated that alterations in the maternal metabolic milieu at any time during gestation can influence intrauterine development and also may have long-term consequences for certain tissues such as adipocytes, myocytes, pancreatic beta-cells, and neurons. This review illustrates that metabolic alterations early in gestation, such as those that occur in diabetes mellitus, may impair growth of the embryo and increase the risk of dysmorphogenesis. Such delayed growth of the embryo may in turn influence size at birth. In midgestation, metabolic perturbations may accelerate functional maturation of fetal pancreatic beta-cells. Fetal beta-cell development is very sensitive to alterations in the nutrient milieu and may be enhanced in gestational diabetes mellitus (GDM) with only minimal elevations of plasma glucose and minor alterations in other nutrient fuels, including insulinogenic amino acids. Data are reviewed that suggest that the ensuing fetal hyperinsulinemia may promote the development of macrosomia even if metabolic control is satisfactory during late gestation. The overall potential influences of metabolic alterations on intrauterine growth are different in pregnancies complicated by diabetes mellitus throughout gestation (pregestational) and GDM. However, the implications in an individual pregnancy may be defined by the degree of metabolic control at the specific stages of gestation when growth of the embryo, development of fetal beta-cell function, and growth of insulin-sensitive tissues are most critically influenced by the metabolic milieu. PMID- 1748277 TI - The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex lethal. AB - Female development in Drosophila is established through the activation of the X:A target gene Sex-lethal (Sxl) by an X:A ratio of 1. X-linked zygotic genes, termed numerator elements, comprise part of the X:A ratio and are primarily responsible for the activation of Sxl in females. We demonstrate that the X-linked segmentation gene runt is required for this process and has genetic and molecular properties of a numerator element. Genetically, runt has vital dose-dependent interactions with components of the X:A ratio and alterations in runt activity alter the sexual phenotype of triploid intersexes. Molecularly, loss of runt activity results in a failure to activate appropriately Sxl in the central region of female embryos. We also show that Sxl activation is influenced by the maternal anterior and terminal pattern-forming genes, bicoid (bcd) and torso (tor). These results indicate that the "uniform" activation of Sxl requires input from nonuniformly distributed products. We have demonstrated that runt is one such product and suggest that other genes with nonuniform input exist. runt is distinguished from previously identified regulators of Sxl by its nonuniform role and by the absence of an identifiable helix-loop-helix (HLH) motif, indicating that the activation of Sxl is not controlled solely by HLH proteins. PMID- 1748278 TI - Analysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene. AB - The let-60 gene of Caenorhabditis elegans controls the choice between vulval and hypodermal differentiation in response to an inductive signal from the gonad. let 60 encodes a ras protein that acts downstream of the let-23 receptor tyrosine kinase in a signal transduction pathway. Dominant-negative mutations of let-60 [let-60(dn)] cause a reduction of the gene activity in let-60(dn)/+ heterozygotes and a vulva-less mutant phenotype. We have found that nine let-60(dn) mutations cause replacements of conserved residues. Four are in two novel positions; others are in positions known previously to cause dominant-negative mutations in mammalian cells. The locations of these lesions suggest that they disrupt the ability of the ras protein to bind guanine nucleotides. Four let-60(dn) mutant genes were introduced into wild-type animals in the form of extrachromosomal arrays and were found to generate three dominant phenotypes--lethality, vulva less, or multivulva--depending on gene dose and alleles. The dominant lethality caused by high-dose transgenic let-60(dn) genes suggests a toxic effect of these mutant genes in early development. The dominant-negative effects of these mutations in heterozygotes are likely to be caused by competition between let 60(dn) and let-60(+) protein for a positive regulator. All let-60(dn) mutations interfere with let-60(+) activity, but some alleles have partial constitutive activity, suggesting that the ability to interact with the activator is separable from the ability to exert a physiological effect (stimulation of vulval differentiation). These dn mutations might be useful for interfering with ras mediated signal transduction pathways in other multicellular organisms. PMID- 1748279 TI - Coactivators for a proline-rich activator purified from the multisubunit human TFIID complex. AB - The mechanisms of transcriptional activation directed by sequence-specific regulators is central to understanding gene regulation. Here, we report the isolation of coactivators responsible for mediating transcriptional activation by Gal4-Pro, a hybrid regulator containing the proline-rich activation domain of human CTF/NFI. Chromatographic studies indicate that endogenous human TFIID consists of a multisubunit complex containing the TATA-binding protein (TBP), coactivators, and other associated factors. A fraction containing the coactivator activity was separated from the endogenous TBP after disrupting the tightly associated complex with urea. The urea-purified TBP was active for basal level transcription but no longer could support activation by Gal4-Pro. However, when the two separated components were added together, activated levels of transcription were restored in the presence of Gal4-Pro. Immunoaffinity purification of the TFIID complex identifies several polypeptides specifically associated with the endogenous TBP, some or all of which function as coactivators when reconstituted with Gal4-Pro. The isolated coactivators also mediate activation by a chimeric glutamine-rich activator derived from Sp1 but not the Gal4-VP16 activator, suggesting distinct factor requirements for different types of transcriptional regulators. PMID- 1748280 TI - Tissue-specific expression of the gene encoding hepatocyte nuclear factor 1 may involve hepatocyte nuclear factor 4. AB - Hepatocyte nuclear factor 1 (HNF-1) is a transcriptional regulatory protein possibly involved in the activation of many liver-specifically expressed genes. HNF-1 mRNA is restricted to a small number of tissues, suggesting that the HNF-1 gene itself is regulated at the transcriptional level. We have isolated and characterized the promoter region of this gene and have determined its transcriptional potential in several cell types by cell-free transcription and transient transfection experiments. In in vitro transcription assays, an HNF-1 promoter is active in nuclear extracts from liver and kidney, two tissues that contain HNF-1, but silent in nuclear extracts from spleen and lung, which are devoid of this transcription factor. Likewise, in transfection experiments, HNF-1 promoter-chloramphenicol acetyltransferase (CAT) fusion genes are expressed in Hep G2 cells, which express HNF-1, but not in mouse L cells or Hela cells, which do not express HNF-1. In both cell-free transcription and transient transfection assays, a relatively short promoter segment located between positions -82 and -40 is necessary and sufficient to direct cell type-specific HNF-1 transcription. This region contains a single site for a DNA-binding protein that has been tentatively identified as hepatocyte nuclear factor 4, a member of the steroid hormone receptor family. PMID- 1748281 TI - Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells. AB - The CT3 cytoplasmic localization mutant of SV40 T antigen is neither properly transported to the nucleus nor is it functional in rodent cells. Human precrisis cells are able to complement this mutation, as they are fully transformed by CT3 with wild-type efficiency. The human-specific factors responsible for this species-specific difference in response to CT3 were localized to human chromosome 6 by synteny in a panel of six somatic cell hybrids. A major human HSP70 heat shock protein located on chromosome 6 is expressed constitutively in human cells. Hsp70 proteins have been reported to play a role in intracellular movement of newly synthesized proteins. To test whether human HSP70 played a role in the complementation by human cells of the defect of CT3, we constructed a series of mouse cell lines expressing human HSP70 and tested them for their ability to localize CT3 T antigen in the nucleus and for their ability to be transformed by CT3 DNA. Mouse cell lines expressing human HSP70 protein were able to translocate mutant CT3 T antigen into the nucleus and were transformed by CT3 at rates comparable with wild-type SV40. Mouse-inducible HSP70 protein was not able to translocate cytoplasmic T antigen in Swiss 3T3 mouse fibroblast cells, even after heat shock. Apparently human HSP70 is capable of complementing directly or indirectly the structural and functional alterations in SV40 T antigen introduced by the CT3 mutation. PMID- 1748282 TI - legless insertional mutation: morphological, molecular, and genetic characterization. AB - Limb morphogenesis is an excellent model system to study pattern formation during vertebrate development. The legless (lgl) insertional mutation can serve as a tool to analyze specific events in limb development at the embryologic, genetic, and molecular levels. Hemizygous mice of this transgenic line are phenotypically normal, but homozygous mutants are inviable and exhibit limb, brain, and craniofacial malformations, as well as situs inversus. By morphological analysis of mutant hindlimb buds we show absence of a normal apical ectodermal ridge, a structure required for limb bud outgrowth, and an unusually high degree of mesenchymal and ectodermal cell death. Mutant embryos are extremely sensitive to retinoic acid, a known teratogen with a proposed role in limb development. The hindlimb malformations in legless mutants are less severe when bred into the BALB/c background, suggesting the involvement of other strain-specific genes. Molecular analysis of the disrupted region indicates two tightly linked insertion sites. Sequences flanking the transgene insertions have been cloned and mapped to chromosome 12, near the iv (situs inversus viscerum) locus. Consistent with this, complementation tests confirm allelism of lgl and iv and suggest that the transgene insertion may have disrupted more than one gene. Phylogenetically conserved sequences flanking the transgene insertions were identified and used to isolate candidate lgl and iv cDNAs. PMID- 1748283 TI - Abnormal brown and white fat development in transgenic mice overexpressing glycerol 3-phosphate dehydrogenase. AB - Mice carrying approximately 25 copies of a transgene encoding glycerol 3 phosphate dehydrogenase expressed from 50 to 200 times the level of enzyme produced by a single copy of the normal endogenous gene. The enzyme constituted greater than 50% of the cytoplasmic protein in the brown fat of a transgenic mouse. Young transgenic mice (10 days to 8 weeks of age) appeared physically and reproductively normal; however, at the earliest times analyzed, the amount of brown fat of transgenic mice was greater than that of nontransgenic littermate controls. In contrast, the white fat depots, both subcutaneous and peritoneal, were severely reduced in size. Brown fat in transgenic mice also had larger lipid vacuoles and lower levels of Ucp mRNA, but Ucp mRNA levels were elevated in response to cold. Brown fat hypertrophy and reduction of white fat were particularly pronounced in aged transgenic animals. The results suggest that development of brown and white fat is altered by overexpression of glycerol 3 phosphate dehydrogenase. PMID- 1748284 TI - Acidic conditions permit effective nodulation of alfalfa by invasion-deficient Rhizobium meliloti exoD mutants. AB - Rhizobium meliloti exoD mutants are deficient in invasion of alfalfa nodules and, as a consequence, the nodules that exoD strains induce fail to fix nitrogen. These nodules appear to be arrested at the same stage as nodules induced by other exo mutants, which do not make an acidic exopolysaccharide called EPS I, or by ndv mutants, which do not produce a periplasmic cyclic beta(1,2) glucan. However previous genetic and biochemical evidence suggested that the nodule invasion defect of exoD mutants arose from a biochemical deficiency distinct from those of both EPS I-deficient exo mutants and ndv mutants. In this study, we characterize mutant phenotypes of exoD strains in both free-living and symbiotic states. Nodules induced by exoD mutants are generally small and empty of bacteria, and exhibit the same structural features as nodules induced by other invasion deficient mutants. Putative incipient infection threads were visible in outer cortical cells of these nodules but not in the plant cells in the interior of the nodule. We show that exoD mutants are sensitive to alkaline conditions, ceasing to grow at elevated pH in liquid yeast extract cultures and exhibiting decreased viability in alkaline medium. Interestingly, we find that buffering the plant growth medium at slightly acidic pH (6.0-6.5) restores the ability of exoD mutants to invade alfalfa nodules. exoD mutants are thus alkali sensitive for both free-living and symbiotic phenotypes. This result implies that the nodule invasion defect of exoD mutants arises from their sensitivity to alkaline conditions and, furthermore, that alkaline conditions may obtain in the developing infection thread. The deduced amino acid sequence of ExoD is extremely hydrophobic, suggesting that the protein is membrane associated. We propose models whereby absence of a putative membrane protein might lead to sensitivity to alkaline conditions and consequent arrest of nodule invasion. PMID- 1748285 TI - Nascent pre-mRNA transcripts are associated with nuclear regions enriched in splicing factors. AB - We have used in situ hybridization and immunocytochemistry to compare the nuclear localization of a specific nascent pre-mRNA and the essential non-snRNP splicing factor SC-35. Nascent c-fos transcripts were detected in serum-induced mouse fibroblasts by in situ hybridization with genomic c-fos probes. Prior to serum induction no c-fos RNA is detected, but these transcripts localize to two dots in the interphase nucleus after induction. The time course of appearance of the dots correlates with the previously determined time course of transcriptional activation of the gene. Upon further analysis by confocal laser scanning microscopy, we have determined that the dots extend through the depth of the nucleus, forming paths. By using high-voltage electron microscopy, we have found that the c-fos path extends out and comes into direct contact with the nuclear envelope. We have also compared the localization of c-fos transcripts with the speckled nuclear regions that are enriched in snRNPs and the non-snRNP splicing factor SC-35. Direct observations of three-dimensional rotations have revealed a close association between the c-fos transcripts and the nuclear speckles. This study demonstrates a direct link between specific nascent RNA transcripts and nuclear speckles that are enriched in pre-mRNA splicing factors. PMID- 1748286 TI - The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. AB - mRNA decay rates often increase when translation is terminated prematurely due to a frameshift or nonsense mutation. We have identified a yeast gene, UPF1, that codes for a trans-acting factor whose function is necessary for enhanced turnover of mRNAs containing a premature stop codon. In the absence of UPF1 function, frameshift or nonsense mutations in the HIS4 or LEU2 genes that normally cause rapid mRNA decay fail to have this effect. Instead, the mRNAs decay at rates similar to the corresponding wild-type mRNAs. The stabilization of frameshift or nonsense mRNAs observed in upf1- strains does not appear to result from enhanced readthrough of the termination signal. Loss of UPF1 function has no effect on the accumulation or stability of HIS4+ or LEU2+ mRNA, suggesting that the UPF1 product functions only in response to a premature termination signal. When we examined the accumulation and stability of other wild-type mRNAs in the presence or absence of UPF1, including MAT alpha 1, STE3, ACT1, PGK1, PAB1, and URA3 mRNAs, only the URA3 transcript was affected. On the basis of these and other results, the UPF1 product appears to participate in a previously uncharacterized pathway leading to the degradation of a limited class of yeast transcripts. PMID- 1748287 TI - Human SRF-related proteins: DNA-binding properties and potential regulatory targets. AB - Serum response factor (SRF) is a transcription factor that binds the sequence CC(A/T)6GG found in a number of growth factor-inducible and muscle-specific promoters. We describe the isolation and characterization of cDNA clones encoding a family of three human SRF-related DNA-binding proteins. Each of these RSRF (related to SRF) proteins contains an 86-amino-acid amino-terminal region related to the SRF DNA-binding domain: In RSRFC4 and RSRFC9, this region is identical, whereas that present in RSRFR2 differs by seven conservative amino acid substitutions. The DNA-binding specificity of the RSRF proteins, which recognize the consensus sequence CTA(A/T)4TAG, is distinct from that of SRF. The entire RSRF common region is required for DNA binding, and the differential sequence specificity of the RSRFs and SRF is the result of differences in the basic amino terminal part of this domain. The RSRF proteins bind DNA as dimers and can dimerize with one another but not with SRF. Although the RSRF mRNAs are expressed in many cell types, RSRFR2 mRNA is expressed at elevated levels in several B-cell lines. Consistent with this, extracts from many cell types form CTA(A/T)4TAG binding complexes that contain RSRF proteins, and oligonucleotides containing RSRF-binding sites function as promoter elements in transfection assays. Like SRF binding sites, RSRF-binding sites are found in the regulatory sequences of a number of growth factor-inducible and muscle-specific genes, and we show that RSRF polypeptides are components of previously characterized binding activities that interact with these elements. We discuss the potential role of RSRF proteins in the regulation of these genes. PMID- 1748288 TI - TFEB has DNA-binding and oligomerization properties of a unique helix-loop helix/leucine-zipper family. AB - The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. This arrangement of interactive motifs has recently been observed in several other transcription factors and in the Myc family of oncogenes. TFEB was isolated by virtue of its binding to the major late promoter of adenovirus. DNA binding by a soluble protein was achieved by deleting a hydrophobic amino-terminal domain and permitted the structural analysis of the oligomerization and DNA-binding properties of TFEB. TFEB specifically bound DNA as both a homodimer and a heterodimer with another b-HLH-LZ protein TFE3. The LZ domain was essential for homo- or hetero-oligomerization and high-affinity DNA binding. In the absence of DNA a tetramer-sized form of TFEB was observed that dissociates to bind added DNA as a dimer. Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences. Analysis of basic domain residues in this family of proteins revealed a pattern of sequence conservation predictive of an interacting alpha-helical face. Common oligomerization and DNA-binding features suggest the b-HLH-LZ domain structure to define a distinct family of DNA-binding factors. PMID- 1748289 TI - LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer. AB - In nuclear extracts of primary murine B lymphocytes cultured with LPS we have identified an inducible DNA-binding activity that is a candidate regulator of isotype-switch recombination. This LPS-responsive factor, which we refer to as LR1, is induced in LPS-cultured primary cells with kinetics that parallel isotype switch recombination. LR1 binds sequences from the S gamma 1, S gamma 3, and S alpha switch regions, as well as the heavy-chain enhancer, and these binding sites define a consensus that occurs in each of the murine switch regions. LR1 activity is present in pre-B and B-cell lines but absent from primary B cells that have not been cultured with mitogen and from highly differentiated B-cell lines. LR1-binding activity depends on phosphorylation and is lost following incubation of nuclear extracts with acid phosphatase. The LPS inducibility and phosphorylation dependence of LR1 activity suggest that this factor monitors kinase-dependent events in cell development and communicates them to the chromosome. The locations of its binding sites and the kinetics of its induction are consistent with a role for LR1 in regulation of isotype switching. PMID- 1748290 TI - Protection of plants against viral diseases by cloned viral genes and anti-genes. PMID- 1748291 TI - Expression of the gene encoding the coat protein of cucumber mosaic virus (CMV) strain WL appears to provide protection to tobacco plants against infection by several different CMV strains. AB - The gene (cp) encoding the coat protein (CP) of cucumber mosaic virus (CMV) strain WL (CMV-WL, which belongs to CMV subgroup II) was custom polymerase chain reaction (CPCR)-engineered for expression as described by Slightom [Gene 100 (1991) 251-255]. CPCR amplification was used to add 5'- and 3'-flanking NcoI sites to the CMV-WL cp gene, and cp was cloned into the expression vector, pUC18cpexp. This CMV-WL cp expression cassette was transferred into the genome of tobacco (Nicotiana tabacum cv. Havana 423) via the Agrobacterium T-DNA transfer mechanism. R0 plants that express the CMV-WL cp gene were subcloned, propagated, and challenge-inoculated with CMV-WL. Several R0 plant lines showed excellent protection against CMV-WL infection; however, plants found to accumulate the highest CP levels did not show the highest degree of protection. Thus in our case, CP levels appear not to be a useful predictor of the degree of protection. Plants from the best protected CMV-WL cp gene-expressing R0 tobacco lines were also inoculated with CMV strains belonging to the other major CMV subgroup (subgroup I), CMV-C and CMV-Chi, and compared in a parallel experiment with a transgenic tobacco plant line that expresses the CMV-C cp gene. Plants expressing the CMV-WL cp gene appeared to show a broader spectrum of protection against infection by the various CMV strains than plants expressing the CMV-C cp gene. PMID- 1748292 TI - Isolation and sequence analysis of TGA1 cDNAs encoding a tomato G protein alpha subunit. AB - We have isolated cDNAs for a gene coding for a G protein alpha subunit from tomato (Lycopersicon esculentum, cv. VF36). This gene, named TGA1, was isolated using a cDNA of the Arabidopsis thaliana G protein alpha subunit-encoding gene, GPA1, as a DNA probe. The sequences of four cDNA clones indicate that the deduced amino acid (aa) sequence of the gene product (TG alpha 1) has 384 aa (44906 Da). The predicted TG alpha 1 protein exhibits similarity to all known G protein alpha subunits. The aa are 84.6% identical and 93% similar (identical and conservative changes) to A. thaliana GP alpha 1, and 34% identical and 59% similar to mammalian transducins. Furthermore, it has all of the consensus regions for a GTP binding protein. Finally, hybridizations of tomato genomic DNA indicate that TGA1 is a single-copy gene. PMID- 1748293 TI - Tissue-specific permutations of self-cleaving newt satellite-2 transcripts. AB - Synthetic transcripts of satellite-2 (sat2) DNA from the newt undergo self catalyzed, site-specific cleavage in vitro using the conserved hammerhead (HH) motif found in a number of infectious plant RNAs. We have analyzed sat2 transcripts from a variety of tissues to obtain evidence for the occurrence of self-cleavage in vivo. We found two distinct types of sat2 transcript populations. Monomeric transcripts in the tests and in somatic tissues such as the liver have ends that map to the in vitro self-cleavage site, and have end groups (5'-hydroxyls and phosphate blocked 3' ends) similar to those produced by self-cleavage. This is the first indication of HH-mediated self-cleavage occurring in animal cells. The monomeric sat2 transcripts found in the newt ovary have a different permutation of the basic DNA repeat sequence. These transcripts begin and end 47 nucleotides upstream from the in vitro self-cleavage site. Despite their apparent lack of utilization of the self-cleavage site, they have end groups which indicate that processing is involved in their formation. PMID- 1748294 TI - The chicken gene encoding the alpha isoform of tropomyosin of fast-twitch muscle fibers: organization, expression and identification of the major proteins synthesized. AB - The chicken gene alpha fTM encoding the alpha-tropomyosin of fast-twitch muscle fibers (alpha fTM) covers 20 kb and consists of 15 exons. From this gene, three types of mature transcripts (1.3 kb, 2 kb and 2.8 kb) are expressed through the use of alternative promoters, alternatively spliced exons and multiple 3' end processing. Northern analysis and S1 mapping have shown that the 1.3-kb transcript (exons 1a, 2b, 3, 4, 5, 6b, 7, 8, 9a-9b) is expressed in fast-twitch skeletal muscles and that 2-kb transcripts are expressed in smooth muscle (exons 1a, 2a, 3, 4, 5, 6b, 7, 8, 9d) and in fibroblasts (exons 1a, 2b, 3, 4, 5, 6a or 6b, 7, 8, 9d). These 2-kb transcripts encode distinct proteins which we have identified by two-dimensional (2D) gel electrophoresis. The 2.8-kb transcript which has not been so far characterized in birds is expressed in brain (exons 1b, 3, 4, 5, 6b, 7, 8, 9c-9d). This transcript has been characterized by a cDNA polymerase chain reaction assay and by S1 nuclease mapping. It produces a major TM isoform of chick brain which we have identified by 2D gels. PMID- 1748295 TI - Cloning and characterization of the promoter of the murine lipoprotein lipase encoding gene: structural and functional analysis. AB - The enzyme lipoprotein lipase (LPL) is responsible for the hydrolysis of triglycerides into free fatty acids and glycerol. Its synthesis is induced as the murine bone marrow stromal cell clone, BMS2, undergoes adipocyte differentiation. The murine genomic LPL promoter has been cloned, sequenced, and characterized by functional and structural assays. The transcriptional start points have been mapped by S1 nuclease and primer extension techniques. Comparison of the 1.7-kb of LPL 5'-flanking sequence between mouse and man reveals 65% identity or greater with conservation of many potential protein-recognition motifs. Using constructs linking this region to the luciferase-encoding reporter gene, transient transfection experiments have documented the promoter function of this sequence in a number of cell lines. Based on a battery of restriction endonucleases, at least 260 bp immediately adjacent to and including the 5'-untranslated region of the first exon are hypersensitive to exogenous nuclease digestion, consistent with an altered chromatin structure. Protein-DNA interactions are detected within this area at the octamer binding protein 1 site and immediately 5' to the translation initiation site based on ExoIII footprinting and gel retention assays. PMID- 1748296 TI - Characterization of the aldose reductase-encoding gene family in rat. AB - Although the enzyme aldose reductase (AR) is implicated in the development of tissue pathology in diabetes, the exact mechanism of this involvement remains unclear. To better understand the role that expression of the aldose reductase encoding gene (ALR) may play in diabetic complications, we have begun to analyze the gene and its regulatory regions, and we present here the sequence of four ALR genes in the rat. The putative functional gene is 14.1 kb long, has ten exons which show perfect sequence identity to the rat lens AR RNA sequence, and nine introns with classical splice-site consensus sequences. Potential regulatory elements in the 5'-flanking region of this gene include a TATA box and two CCAAT boxes. Probing rat genomic Southern blots with a fragment from the first intron indicates that there is probably only one copy of this gene in the rat genome. The other three genes are processed pseudogenes which show approx. 90% identity to the rat lens AR RNA sequence, contain no introns, and have poly(A) regions at their 3' ends. Chromosomal localization studies show the presence of ALR genes on chromosomes 3, 4 and 6 in the rat with the putative functional gene mapped on chromosome 4. PMID- 1748297 TI - The assembly of functional preinitiation complexes and transcription of 5S RNA encoding genes containing point mutations. AB - The transcription of several Syrian hamster 5S RNA-encoding genes (5S genes) containing single and multiple point mutations in and around the intragenic control region has been analyzed in a HeLa cell-free system. Although most genes with point mutations displayed normal levels of transcription, several exhibited a three- to fivefold reduction in transcription. These mutations interfere with the interaction between the 5S genes and the soluble factors. The above studies help to establish the importance of specific nucleotides within the 5S gene for productive interactions of individual transcription factors in vitro. PMID- 1748298 TI - High-level secretion of correctly processed recombinant human interleukin-1 beta in Kluyveromyces lactis. AB - The lactose-assimilating yeast, Kluyveromyces lactis, has been developed as a microbial host for the synthesis and secretion of human proteins. Here, we report the use of multi-copy vectors based on the 2 mu-like plasmid pKD1 from Kluyveromyces drosophilarum [Chen et al., Nucleic Acids Res. 14 (1986) 4471-4481] for the secretion of recombinant human interleukin-1 beta (reIL-1 beta). High levels of reIL-1 beta were secreted into the growth medium when the structural gene was fused in-frame to a synthetic secretion signal derived from the 'pre' region of the K. lactis killer toxin. N-terminal sequencing of the excreted protein showed highly efficient (greater than 95%) maturation of the signal sequence. Synthesis as prepro-IL-1 beta, the 'pro'-sequence being derived from the human serum albumin-encoding gene, resulted in equally efficient secretion of mature IL-1 beta. Cytoplasmic production of Met-IL-1 beta, without a secretion signal, was found to be toxic to K. lactis. As in Saccharomyces cerevisiae [Baldari et al., EMBO J. 6 (1987) 229-234], but unlike native human IL-1 beta, K. lactis reIL-1 beta is glycosylated. This glycosylation led to a 95% loss of its biological activity. Removal of the carbohydrate chains by endo-beta-N-acetyl glucosamidase H treatment fully restored the biological activity. A modified form of IL-1 beta (Asn7----Gln7), in which the unique site for Asn-linked glycosylation was deleted, exhibited the same biological activity as native IL-1 beta. The level of secretion of mature recombinant IL-1 beta ws glycosylation independent. PMID- 1748299 TI - Synthesis and functional characterization of a recombinant monoclonal antibody directed against the alpha-chain of the human interleukin-2 receptor. AB - We have determined the sequence of the light and heavy chains of mAb 3G-10 (IgG1), a monoclonal antibody competing with interleukin 2 (IL2) for binding to the human IL2 receptor Tac protein. The antibody-encoding genes were chimerized by introducing splice donor and part of the intron sequences into the cDNA and subsequently linking it to the constant parts of the human IgG1 gene. The chimeric mAb was produced in mouse myeloma cells and purified. Murine and chimeric mAbs showed similar properties with respect to inhibition of T-cell proliferation. In contrast to its murine counterpart, the chimeric mAb exhibited Ab-dependent cellular cytotoxicity and, when combined with an Ab recognizing a different epitope on the IL2 receptor Tac protein, was able to activate human complement. The chimerized mAb might therefore have improved therapeutic efficacy. PMID- 1748300 TI - Cloning and characterization of the gene encoding bovine mitochondrial adenylate kinase isozyme 3. AB - The structure of the gene (AK3) encoding bovine mitochondrial (mt) adenylate kinase isozyme 3 (AK3) has been determined. The gene spans about 46 kb and splits into five exons. The 5'-flanking region of the gene lacks typical transcriptional regulatory elements such as TATA and CAAT boxes. The G + C content of this region is high (71%), and seven GC boxes are recognized. Possible sequences responsive to transcription factors, AP-1, AP-2, Myf-6 and MyoD1, are present in this region. In the 5'-flanking region, there are sequences (mt sequence) which were found in the genes encoding other mt proteins. Transcriptional mapping analyses revealed one major mRNA start point. The promoter activity measurement in Chinese hamster ovary cells by transient expression of the cat gene connected with the 5' flanking region, showed presence of a functional promoter. PMID- 1748301 TI - Cloning and characterization of gene TNF alpha encoding equine tumor necrosis factor alpha. AB - We report the molecular cloning and nucleotide sequence of the equine gene encoding tumor necrosis factor alpha. The 2610-bp genomic sequence was derived from three overlapping polymerase chain reaction products. PMID- 1748302 TI - Cloning of an activated human ret gene with a novel 5' sequence fused by DNA rearrangement. AB - By transfecting a high-Mr DNA from human stomach cancer into NIH3T3 cells, a transforming sequence that showed homology with the human ret gene was identified. The transforming sequence was found to be generated by a DNA rearrangement in the human ret proto-oncogene. This rearrangement was suggested to have occurred during the transfection procedure. The nucleotide sequences of cDNAs of the rearranged ret gene and deduced amino acid (aa) sequences revealed that the rearrangement had resulted in recombination of the 3' segment of the ret proto-oncogene with a segment of an unknown human sequence, and that the recombination had generated a novel gene encoding a fusion protein of 435 aa. The rearrangement was presumed to be responsible for activation of the ret gene. PMID- 1748303 TI - Cloning and sequencing a cDNA encoding human ribosomal protein S25. AB - A full-length cDNA clone has been isolated from a cDNA library prepared from mRNA of adriamycin-resistant human leukemia HL60 cells. The nucleotide sequence of this cDNA has been determined and the protein coded for by the gene identified. The cDNA encodes a polypeptide of 125 amino acids (aa) with a deduced Mr of 13750. The deduced aa sequence of this protein has 56% homology to yeast ribosomal protein S31. Western-blot analysis using antibodies directed against a synthetic peptide based on the deduced aa sequence identifies the gene product as the human ribosomal protein S25. PMID- 1748304 TI - A Drosophila melanogaster H3.3 cDNA encodes a histone variant identical with the vertebrate H3.3. AB - A cDNA encoding an H3.3 histone variant in Drosophila melanogaster predicts a protein with an amino acid (aa) sequence identical with that in vertebrates. The D. melanogaster H3.3 nucleotide (nt) sequence has diverged significantly from that of both the H3.3 gene of vertebrates and the H3.1 gene of D. melanogaster, largely through third nt changes in its codons. The perfect H3.3 aa sequence conservation between organisms as phylogenetically divergent as vertebrates and flies suggests that the H3.3 histone variant itself is an important structural component of chromatin, apart from the value of its replication-independent expression pattern. PMID- 1748305 TI - Primary structure of the embryo-expressed gene KE2 from the mouse H-2K region. AB - Nucleotide (nt) sequence of the KE2 wild-type (wt) cDNA revealed a novel 669-bp open reading frame encoding a putative hydrophilic protein of 127 amino acids, pI 6.17. Comparison of the wt to the genomic nt sequence from the tw5 mutant shows the KE2 gene is conserved and is probably a functional gene unrelated to the tw5 lethality. PMID- 1748306 TI - Three pseudogenes for human U13 snRNA belong to class III. AB - The nucleotide sequences of three pseudogenes for the small nucleolar RNA, U13, were determined from three human DNA clones. The sequences are reported 50 bp 5' and 3' to each gene. These pseudogenes belong to class III because they contain dispersed mismatches when compared to the previously determined U13 RNA sequence, an adenine-rich region at the 3' end, and short imperfect repeats flanking the 5' end of the coding sequence and the 3' end of the adenine-rich region. PMID- 1748307 TI - Importance of the CArG box in regulation of beta-actin-encoding genes. AB - The beta-actin-encoding gene (Act) in carp is regulated by several cis-acting regulatory elements including the evolutionarily conserved CC(A/T)6GG (CArG box or serum-response element) sequences positioned in the promoter region between the CAAT and TATA boxes and in the first intron. To address the roles of the two CArG boxes on gene expression, we replaced them with linker sequences. The CArG box in the proximal promoter was not required for promoter activity in tissue cultured cells, but was required in conjunction with a second CArG box in the first intron to give full expression in transgenic embryos. Likewise, the geometry of cis-acting transcriptional elements in the proximal promoter was more important for expression of transgenic constructs in developing embryos than in tissue-cultured fibroblasts. Mobility-shift and exonuclease mapping experiments indicated that the same or similar protein factors bind around the two CArG boxes, suggesting that interactions between the promoter and the first intron are involved in Act regulation. PMID- 1748308 TI - DNase I-hypersensitive sites are associated, in a tissue-specific manner, with expression of the calbindin-D9k-encoding gene. AB - We have examined the chromatin structure of a 28-kb chromosomal region containing the gene (CaBP9k) encoding calbindin-D9k in different rat tissues. DNase I hypersensitive sites (HSs) were probed with DNase I using an indirect end labeling technique. Duodenal chromatin, where the gene is strongly expressed, contained one major HS (HS4) and three minor HSs (HS2, HS3 and HS5) near the promoter region. The HS4 was mapped just upstream from the promoter region and had the characteristics of a tissue-specific HS. The HS5 was located at the transcription start point, it included the TATA box and its presence was correlated with a promoter function. The duodenal chromatin contained two additional HSs, a major HS (HS1) located approx. 3.5 kb upstream from the cap site and a minor HS (HS6) in the second intron at +0.5 kb. Despite the marked effect of 1,25-dihydroxyvitamin D3 (DHD3) on the CaBP9k mRNA level, the pattern of HSs in duodenal chromatin was unchanged after stimulation with DHD3. The liver chromatin contained one major HS (HS1) identical to the duodenum HS1 (although this tissue does not express CaBP9k). It also contained a liver-specific HS (HS0) 0.1 kb upstream from HS1. The interaction of HS0 with HS1 could explain the absence of CaBP9k expression in the liver. Thus, specific sets of HSs are associated with various functional states of CaBP9k in a tissue-specific manner. PMID- 1748309 TI - A novel method for generating stable high-level transfectants involving direct immunomagnetic selection for cell-surface epitopes: expression of HLA class-II genes in HeLa cells. AB - A versatile method that allows efficient detection and selection of both transient and stable transfectants expressing exogenous cell-surface molecules is described and used to generate stable HeLa transfectants expressing each of the human HLA class-II isotypes, specifically the DR1, DQw8 and DPw2 heterodimers. The method combines use of the strong mammalian expression vector, CDM8, and a highly efficient transfection protocol with the powerful technique of immunomagnetic selection. It offers significant advantages in comparison to standard procedures involving co-selection with drug-resistance markers. The transfection efficiency can be assessed 60 h after transfection rather than after three weeks of drug selection. Repeated rounds of immunomagnetic selection applied over the subsequent ten days result in homogeneous populations which express the surface marker of interest stably at high levels, making further subcloning or fluorescence-activated cell sorting unnecessary. Any number of surface products can be transfected into the same cell, the only limitation being the availability of specific monoclonal antibodies (a DP/DR double transfectant is described expressing four exogenous gene products simultaneously). The high sensitivity of immunomagnetic selection and its applicability to large samples allows rescue of transfectants present at very low frequencies. Finally, the technique can be used as a coselection procedure, by analogy with drug coselection, to achieve expression even of non-cell surface products. PMID- 1748310 TI - Synthesis of human initiation factor-2 alpha in Saccharomyces cerevisiae. AB - A human eIF-2 alpha cDNA (encoding alpha-subunit of the eukaryotic initiation factor-2) was expressed under the control of the galactose-regulated GAL1, 10 promoter, in Saccharomyces cerevisiae, in order to study the possible interactions of human eIF-2 alpha with the yeast protein synthesis apparatus. Isoelectric focusing coupled with Western-blot analysis demonstrated that the human eIF-2 alpha subunit synthesized in yeast under a variety of growth conditions was detected as two bands which co-migrated with the phosphorylated and unphosphorylated forms of rabbit eIF-2 alpha, suggesting covalent modification in vivo. Cell fractionation studies further demonstrated that the synthesised human eIF-2 alpha protein, though present in the cytoplasm, was largely associated with the yeast ribosomes, but could be removed from these by washing with 0.3 M KCl. This possible association of the synthesised human subunit into a three-subunit (alpha, beta and gamma) eIF-2 complex was further examined by partial purification of the yeast eIF-2 complex and estimation of the molecular mass of this complex. Immunoreactive eIF-2 alpha was found in fractions with eIF-2 activity and the estimated molecular mass (130 kDa) corresponded to that predicted for the eIF-2 trimer. These analyses suggest that human eIF-2 alpha subunit synthesised in yeast can become involved with the yeast protein synthetic apparatus, though whether this is a functional incorporation requires further genetic studies. PMID- 1748311 TI - Isolation and analysis of cDNAs encoding small GTP-binding proteins of Arabidopsis thaliana. AB - We previously isolated a DNA fragment from Arabidopsis thaliana homologous to the mammalian ras gene and named it ara [Matsui et al., Gene 76 (1989) 313-319]. Screening of cDNA clones homologous to ara in A. thaliana resulted in the isolation of four homologous genes. The products of these genes, ARA-2, ARA-3, ARA-4 and ARA-5, showed conservation of amino acids (aa) in four regions, all of which are present in small GTP-binding proteins, and are important for GTPase/GTP binding activities. These products were highly homologous to those of the YPT genes of Saccharomyces cerevisiae and the ypt gene of Schizosaccharomyces pombe in the regions around aa 45, which is thought to be the site interacting with effector molecules. The products of these four genes showed characteristic aa sequence at their C termini, Cys-Cys-Xaa-Xaa. Another characteristic of this family is presence of Ser in place of Gly in the first conserved region (Gly12 of mammalian GTP-binding Ras protein). PMID- 1748312 TI - Characterization of potentially functional 5S rRNA-encoding genes within ribosomal DNA repeats of the nematode Meloidogyne arenaria. AB - In the plant-parasitic nematode Meloidogyne arenaria, isolated rDNA repeats show length heterogeneity, and are unusual in that they contain putative 5S ribosomal RNA pseudogenes [Vahidi et al., J. Mol. Evol. 27 (1988) 222-227]. Potentially functional 5S rRNA-encoding genes can also be identified in various rDNA repeats, which appear to be tandemly organized in the genome. PMID- 1748313 TI - Cloning and analysis of a cDNA encoding a human liver carboxylesterase. AB - A human liver carboxylesterase (CE)-encoding cDNA has been cloned using synthetic oligodeoxyribonucleotides (oligos) based on the known amino acid (aa) sequences of rabbit and rat liver CEs. The oligos hybridize specifically to DNA encoding liver CEs. The longest cDNA obtained from screening several cDNA libraries encodes about 80% of the protein and translates into an aa sequence which has a high degree of similarity with the sequences of liver CEs from other species. On hybridization to mRNA isolated from human liver, the cDNA gave a single band of about 2.0 kb consistent with its encoding a protein of less than 68 kDa. DNA obtained from a number of human livers and probed with the CE cDNA gave identical hybridization patterns. These patterns were moderately complex by comparison with published data. PMID- 1748314 TI - Nucleotide sequence and expression of the human gene encoding apolipoprotein H (beta 2-glycoprotein I). AB - Human apolipoprotein H (ApoH), also called beta 2-glycoprotein I, is a 50-kDa serum glycoprotein whose function is not clearly defined. We have cloned and sequenced ApoH cDNAs both from human liver and from a human hepatoma cell line (HepG2). Both cDNA sequences predict a protein 345 amino acids (aa) in length. This sequence includes a 19-aa hydrophobic, N-terminal signal sequence which is not present in the mature protein [Lozier et al., Proc. Natl. Acad. Sci. USA 81 (1984) 3640-3644]. It differs from this previously reported aa sequence at two positions, both of which strengthen the conservation among the four short consensus repeats within the ApoH molecule. COS-1 cells transiently transfected with the ApoH cDNA in a eukaryotic expression vector produced a single species of ApoH mRNA and secreted in the ApoH protein. The level of ApoH mRNA expressed by HepG2 cells is downregulated by incubation with inflammatory mediators, implying that ApoH is a negative acute-phase protein. PMID- 1748315 TI - Nucleotide sequences of two members of the chicken H4 histone-encoding gene family. AB - The nucleotide sequences of two genes (H4-III and H4-IV) from the chicken H4 histone-encoding gene family have been determined. The four H4 genes, including the previously sequenced H4-I and H4-II genes, encode the same amino acid sequence and possess several copies of the possible Sp1-binding sequences on the coding and noncoding strands within the 5'-flanking regions. PMID- 1748316 TI - Sequence of the chicken rig gene encoding ribosomal protein S15. AB - The nucleotide sequence of the chicken rig gene encoding ribosomal protein S15 was determined. The 1.6-kb gene consists of four exons and three introns. The 5' flanking region of the gene lacks TATA- or CAAT-box sequences. Several GC-box sequences were found around the transcription start point. PMID- 1748317 TI - Evaluation of the improvement of cephems on the prophylaxis of pelvic infection after radical hysterectomy. AB - Antibiotics, especially cephems, have been improved remarkably in the last 20 years. In order to evaluate the improvement of antibiotics used for the prophylaxis of infections after radical hysterectomy, two groups of patients (group A, 1978-1979, n = 54; group B, 1985-1987, n = 55) were examined in regard to bacteriological and clinical effects. In spite of the improvement of antibiotics, the positive rate of bacteriological analysis had increased from 44.4 to 76.4%. Obvious decrease of gram-negative bacilli and increase of gram positive cocci (GPC), e.g. Enterococcus, were observed. In contrast, fever index and febrile morbidity of group B decreased significantly more than those of group A. These results indicate that the improvement of antibiotics has brought more effective prophylaxis in the postoperative infection in spite of the high positive rate of GPC. PMID- 1748318 TI - Ultrasonic Doppler flow studies of the uterine arteries in women with cervix cancer. AB - The main characteristic of malignant tumors is their capacity for local destructive spread as well as infiltration into the adjacent tissue. The present study was carried out to evaluate the hemodynamic alterations in patients with advanced cervix cancer. Data of 34 patients with cervix cancer are compared to 30 healthy women with normal history. The mean pulsatility index (PI) was significantly lower in cancer patients (PI = 1.75 +/- 1.27) than in controls (PI = 3.18 +/- 0.99). Use of noninvasive Doppler ultrasound study physiology of uterine hemodynamics in patients with cervix cancer is of great clinical relevance and paves the way for further investigations in screening programs for cervix cancer. PMID- 1748319 TI - Myometrial invasion of endometrium cancer assessed by transrectal ultrasonography. AB - Transrectal ultrasonographic examinations before surgery were performed on 27 patients with stage I endometrial cancer to assess myometrial invasion. The findings were compared with the histopathologic data obtained by surgery. Sensitivity and specificity of transrectal ultrasonography in myometrial invasion of endometrium cancer were 82.6 and 100%, respectively. Therefore, transrectal ultrasonography may be a useful diagnostic tool to determine the myometrial invasion, which is the most important prognostic factor in endometrial cancer. PMID- 1748320 TI - Consecutive pregnancies in a menopausal woman following oocyte donation. AB - A second pregnancy was successfully achieved by a menopausal women who had previously conceived and delivered an infant using donated oocytes. The same nonanonymous oocyte donor provided the gametes for both procedures. Prior to embryo transfer, the functionally agonadal recipient received exogenous steroid hormone replacement therapy. Both pregnancies followed the transfer of 5 embryos which were conceived by the in vitro fertilization of the donated oocytes with the recipient husband's sperm. The first pregnancy ended with an intrauterine fetal demise at 40 weeks gestation. The second pregnancy is proceeding unremarkably. PMID- 1748321 TI - A technique for vaginal casting utilizing vinyl polysiloxane dental impression material. PMID- 1748322 TI - Effect of zinc supplementation in a Turkish woman with two previous anencephalic infants. AB - The authors report a case of nutritional zinc deficiency in a young (18-year-old) Turkish woman, who previously delivered 2 anencephalic stillborn infants. The patient was supplemented with 22.5 mg oral zinc sulfate (100 mg ZnSO4.7H2O) for 5 months after her second delivery prior to her third pregnancy. Her blood (plasma and red blood cell) and hair zinc levels returned to normal following zinc supplementation. Good response to Zn supplementation was another criterion of Zn deficiency in this particular case. After an uneventful gestational period, she delivered an apparently normal full-term male child who has grown normally during the first 12 months. PMID- 1748323 TI - Preoperative diagnostic imaging of primary vaginal carcinoma by transvaginal color Doppler and magnetic resonance imaging. AB - We treated a patient with primary vaginal carcinoma. Very valuable preoperative diagnostic imaging of the carcinoma obtained by transvaginal color Doppler and magnetic resonance is reported herein. PMID- 1748324 TI - Effects of ketanserin--a serotonin receptor antagonist--on placental blood flow, placental weight and fetal weight of spontaneously hypertensive rats and normal Wistar Kyoto rats. AB - Recently, ketanserin (serotonin receptor antagonist) has been reported to be beneficial in the treatment of preeclampsia. In this study, we investigated the effects of ketanserin on the placental blood flow, fetal weight and placental weight in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). We measured the rats' placental blood flow by monitoring the clearance of hydrogen gas generated by electrolysis. In ketanserin (12, 24, 48 mg/kg)-treated SHR, systolic blood pressure was significantly decreased. The placental blood flow was significantly (p less than 0.05) reduced compared to that before treatment in WKY and SHR. The fetal weight decreased dose dependently in WKY, while in SHR it did not decrease significantly. The placental weight of ketanserin-treated rats decreased compared to that before treatment. These data suggest that ketanserin might have some reducing effects on placental blood flow, fetal weight and placental weight proportional to the dose. PMID- 1748325 TI - Outcome of ovarian response after suppression with a gonadotropin releasing hormone agonist in different chronological periods prior to gonadotropin stimulation for in vitro fertilization. AB - Gonadotropin-releasing hormone analogues (GnRH-a) are currently used in combination with gonadotropins in ovarian stimulation for in vitro fertilization programs (IVF). The present study aims at evaluating the treatment cycles for IVF for which human menopausal gonadotropin (HMG) was initiated only when pituitary desensitization was confirmed regardless of the time of GnRH-a administration. Two groups of patients were examined. Patients in group A (n = 46) were commenced with HMG treatment on day 15 when E2 level was less than 40 pg/ml. Group B patients (n = 27) comprised the cycle treatments in which E2 levels were greater than 40 pg/ml on day 15. In these cases HMG was first given when E2 levels declined to less than 40 pg/ml. The fertilization rate was similar in both A and B groups, 71.6 and 67.7% respectively. The pregnancy rate per transfer was 27.5 and 34.6% in group A and B respectively. Multiple pregnancies were found at 18.1% in group A versus 44.4% in group B. It is concluded that postponement of HMG administration in patients with high levels of E2 on day 15 after GnRH-a administration seems to offer an improvement in embryo cleavage speed, pregnancy rate and multiple pregnancies. PMID- 1748326 TI - Second-trimester thyroid function and pregnancy outcome in mothers with hyperthyroidism. Birth weight related to mid-trimester triiodothyronine and RBC zinc. AB - Thyroid function at 24-28 weeks gestation was compared between 26 mothers with hyperthyroidism (16 on antithyroid treatment and 10 in remission without treatment) and 15 normal pregnant controls. There was no difference in the total and free thyroxine (TT4 and FT4) or in the total and free triiodothyronine (TT3 and FT3) concentrations, but the erythrocyte zinc (RBC Zn) concentration was significantly lower in the study group (187.3 +/- 46.6 mumol/l RBC versus 223.6 +/- 3.7 mumol/l RBC, p less than 0.01). In the study group, both birth weight and gestation at delivery were significantly correlated with TT3 (r = -0.500, p less than 0.02 and r = -0.460, p less than 0.05, respectively) as well as with RBC Zn (r = 0.473, p less than 0.02 and r = 0.573, p less than 0.01, respectively). The results suggest that plasma concentration of TT3 and of RBC Zn at 24-28 weeks gestation may be helpful prognostic factors in the management of pregnant patients with hyperthyroidism. PMID- 1748327 TI - Antenatal nutritional assessment: the value of upper arm circumference. AB - Nutritional indicators such as prepregnant weight or weight increase during pregnancy are often difficult to use in developing countries. The value of the mid-upper-arm circumference was therefore analyzed in a study of 833 Mozambican gravidae, mainly seen at community level. Arm circumference was associated with both the estimated prepregnancy weight (p less than 0.0001) and the arm muscle circumference (p less than 0.0001). Of the studied women, 4% had an arm circumference below 23 cm, and 69% of these women had an estimated prepregnant weight for height below 85% of standard. An arm circumference below 25 cm was encountered in 24% of the studied group, and 11 out of these 24% were below 85% of estimated prepregnancy weight for height. In Mozambican gravidae a mid-upper arm circumference below 25 cm is a warning of malnutrition and below 23 cm is a strong indicator of malnutrition. PMID- 1748328 TI - Can terbutaline be used as a nebuliser instead of intravenous injection for inhibition of uterine activity? AB - Terbutaline, a betamimetic drug, is used as bolus of 0.25 mg intravenously to inhibit uterine activity when encountered with uterine hyperstimulation and associated fetal heart rate changes. The effect of terbutaline used as a nebuliser in 1- and 2-mg doses on uterine activity in labor was investigated. It did not show any significant inhibition of the uterine activity in spontaneous term labor. Although convenient and easy to administer especially in an emergency, 1 or 2 mg terbutaline used in the form of nebuliser did not give the desired effect like 0.25 mg of terbutaline given intravenously for inhibition of uterine activity in term labor. PMID- 1748329 TI - Meteorological factors in hypertensive disorders, vaginal bleeding and premature rupture of membranes during pregnancy. AB - In order to determine whether there is a correlation between meteorological factors and the occurrence of hypertensive disorders, vaginal bleeding during pregnancy and premature rupture of the fetal membranes, we stratified all the patients hospitalized with such complications between the years 1984 and 1988 by the months of occurrence, weather, humidity and heat. During this period, there were 276 women hospitalized with exacerbation of hypertension and toxemia, 349 because of vaginal bleeding during pregnancy and 35 women following premature rupture of the fetal membrane between 30 and 33 weeks of gestation. The occurrence of pre-eclampsia and exacerbation of pregnancy-induced hypertension was significantly increased in the winter months (p less than 0.001). PMID- 1748330 TI - Evaluation of the possible interaction of the antifungal triazole SCH 39304 with oral contraceptives in normal healthy women. AB - The possible interaction of the newly developed triazole antifungal SCH 39304 with low-dose combined oral contraceptives (OCs) was studied in 15 healthy women. Serum levels of ovarian and adrenocortical steroids and sex hormone-binding globulin (SHBG) were analyzed in samples collected during the OC cycles immediately before, during and after the administration of SCH 39304. The drug was given as a single 400-mg oral dose on day 7 in the second cycle. SCH 39304 did not interfere with the ovulatory inhibitory action of low-dose combined OCs as judged from serum progesterone values. Administration of SCH 39304 caused minor decreases in serum SHBG, cortisol and dehydroepiandrosterone sulfate. The mechanism(s) behind these minor changes is not known. PMID- 1748331 TI - Comparison of oral contraceptive use in women with adenocarcinoma and squamous cell carcinoma of the uterine cervix. AB - The possible link between oral contraceptives (OCs) and cervical adenocarcinoma was tested by a case-case study of prior and current OC use in women with adenocarcinoma and squamous cell carcinoma. Cases were matched by age, year of diagnosis, and stage of the lesion, and personal, reproductive, and contraceptive data were obtained by mailed questionnaires. Except for smoking, which was significantly more prevalent in women with squamous cell carcinoma, the two groups were identical, with similar OC exposure. This study does not support the idea that OCs modulate the expression of cervical neoplasia in favor of adenocarcinoma. PMID- 1748332 TI - [Immediate breast reconstruction with tissue expander]. AB - The technique of immediate breast reconstruction, using the tissue expander and replacing it with a permanent silicone prosthesis, has been applied with increasing frequency during the past several years. We chose this technique for immediate breast reconstruction because of its simplicity, rapidity when combined with mastectomy, and good esthetic results. We have performed 29 immediate breast reconstructions in the past 1.5 years in patients ranging from 22 to 72 years (mean 47). The insertion of the tissue expander added only 20-30 minutes of operating time for the mastectomy, and did not prolong hospitalization. Before we began to replace the expander with a permanent silicone prosthesis there were complications in 4 patients (14%). These included development of a seroma in 3, 1 of which became infected 40 days after insertion of the tissue expander, and capsular contraction in a patient who had previously had radiotherapy to her breast. The case with the infection was the only failure and the expander had to be removed. Immediate reconstruction of the breast is easily performed and can be of tremendous psychological benefit to mastectomy patients. Chemotherapy or radiotherapy are not contraindications to this type of reconstruction. PMID- 1748333 TI - [The professional historical mistake: psychiatric aspects]. AB - The concept of the professional historical mistake (PHM) pertains to a wide spread, deep seated, narrow professional attitude which has prevailed for many years, or decades, and fails to take into consideration existing professional knowledge, which would broaden the narrow professional approach. 3 cases of PHM in psychiatry are discussed. It is believed that PHM occur in medicine, and since they tend to be overlooked, conscious effort to detect them is needed in order to prevent or to halt them. PMID- 1748334 TI - [Unusual presenting symptoms of hypothyroidism]. AB - The assumption that hypothyroidism has a typical presentation can lead to error. Although a common disease in adults and easily treated, the diagnosis can be missed for years. Failure to recognize the rare signs and symptoms of hypothyroidism leads to unnecessary morbidity and rarely, even to death, from myxedema coma. We discuss a number of cases which presented over the past few years with less recognized symptoms, such as convulsions, acute psychosis, neuromuscular disturbances and deafness. Other atypical presenting symptoms that have been described include intestinal pseudo-obstruction and bleeding disorders. One should be aware of these varied presentations of hypothyroidism. PMID- 1748335 TI - [Subcutaneous emphysema as a complication of colonoscopy]. AB - A 71-year-old man underwent colonoscopy and multiple poly-pectomy. A few hours after the procedure he developed massive subcutaneous emphysema of the abdomen, chest, mediastinum, scrotum and both legs. Treatment was by conservative measures only. The emphysema gradually disappeared and he was discharged within a few days without sequelae. Subcutaneous emphysema is a rare complication of colonoscopy which has also been described after other endoscopic and radiological investigations of the gastrointestinal tract. It is due to a tiny laceration of the mucosal wall of the colon incurred during aggressive instrumentation, through which pass large quantities of air. The laceration is located underneath the peritoneal sac and the air flows into the retroperitoneum (closed or extraperitoneal perforation). The appearance of subcutaneous emphysema a few hours later, usually after leaving the hospital, is characteristic. In contrast to intraperitoneal perforation (open perforation), surgical intervention is not indicated and treatment is usually conservative. It includes complete cessation of oral alimentation, insertion of a nasogastric tube, IV drip, and correction of hydro-electrolytic or acid-base imbalances. The overall prognosis following such measures is excellent. PMID- 1748336 TI - [Fentanyl vs alfentanil anesthesia for in vitro fertilization]. AB - In a prospective double-blind study, 36 women undergoing ultrasonically guided oocyte retrieval for in vitro fertilization (IVF) were examined. Anesthesia in 19 was based on alfentanil, up to 0.025 mg/kg and in 17, fentanyl, 0.0025 mg/kg. There were no significant differences between groups with regard to age, weight, duration of procedure and pregnancy rate. There were no complications aside from nausea and vomiting. Amnesia for the puncture and analgesia were always perfect. Induction was significantly shorter for alfentanil, 1.3 +/- 0.7 min, than for fentanyl, 3.4 +/- 2.2 (p less than 0.01). All who received fentanyl were drowsy at the end of the procedure, while those in the alfentanil group were fully awake and able to move from operating table to stretcher with minimal help. We therefore recommend alfentanil as the base for anesthesia for IVF. PMID- 1748337 TI - [Parathyroid adenoma in a child]. AB - Parathyroid adenoma presenting as primary hyperparathyroidism is rare in childhood. We report a case in a 9-year-old Bedouin girl. The diagnosis was based on hypercalcemia, which was found accidentally, and elevated serum parathyroid levels. Ultrasonography, scintigraphy, computerized tomography and magnetic resonance imaging failed to detect the lesion. The diagnosis was only established at exploratory operation, when an adenoma was removed from the right upper pole of the thyroid. PMID- 1748338 TI - [Cytogenic accuracy of chorionic villus sampling and second trimester amniocentesis: is early amniocentesis an alternative?]. PMID- 1748339 TI - [Medical malpractice in Israeli court judgements and defensive medicine: is it possible to restore trust between patients and physicians? Part I: Judgements regarding medical practice]. PMID- 1748340 TI - ["You shall not ... incise any marks on yourselves" practical, medical and legal aspects of tattooing]. PMID- 1748341 TI - [Heart-lung and lung transplantation in cystic fibrosis]. PMID- 1748342 TI - [Therapeutic sport]. PMID- 1748343 TI - [Primary brain lymphoma]. AB - Between 1973 and 1989, 739 patients with non-Hodgkin's lymphoma were referred here for treatment, of whom 10 (1.4%) had primary brain lymphoma (PBL) and 1 had acquired immunodeficiency syndrome (AIDS). There were 7 females and 3 males (mean age 58 years, range 35-77). Duration of symptoms ranged from several days to 3 weeks. The presenting symptoms were secondary to increased intracranial pressure. Computerized tomography (CT) performed in 8 revealed a solitary lesion in 7. Other CT scan features were various degrees of contrast enhancement, edema and midline shift. The most common site was the frontal lobe; infratentorially, the cerebellum was the most frequent site. The diagnosis was established in 8 patients by surgery and in 2 at autopsy. The most common subtype was the diffuse, large cell, immunoblastic lymphoma. 5 patients were irradiated following subtotal excision and 2 had combined radiation therapy and high-dose methotrexate-based chemotherapy; only 1 had no postoperative treatment. All patients treated by radiotherapy alone died within 3-5 months after diagnosis. The 2 who received combined therapy are alive, 15 and 48 months after diagnosis, respectively. PMID- 1748344 TI - [Quality of life in hypertensive patients]. PMID- 1748345 TI - [Relationship between left ventricular pressure and volume, and its relation to oxygen consumption]. PMID- 1748346 TI - [Antithrombotic therapy in coronary intervention: angioplasty and coronary bypass surgery]. PMID- 1748347 TI - [New molecular technology in prenatal genetic diagnosis]. PMID- 1748348 TI - [Use of remedies--precept or option?]. PMID- 1748349 TI - [Seasonal changes in sperm quality]. PMID- 1748350 TI - [Bibliography--the achilles heel of medical articles]. PMID- 1748351 TI - [Fever and splenic space-occupying lesion in a diabetic]. PMID- 1748352 TI - [Outcome of immediate management of severe head injuries]. AB - Immediate management of severe head injuries still poses a serious challenge. 50 patients with severe head injuries (Glasgow Coma Scale, 8 or less) were treated from February 1, 1989 to April 30, 1990. The effects of age, Glasgow Coma Score at admission, CT findings, pupillary reactivity to light and intracranial pressure on outcome, were evaluated. The results of the present series match those of other studies and in some aspects the results are even superior. We attribute the high incidence of good outcome to the direct referral of the severe head injury patients, thus excluding delays at peripheral hospitals. In addition, aggressive management in the intensive care units and a broader range of indications for operation were also correlated with favorable outcome. PMID- 1748353 TI - Isomeric amphetamines--a problem for urinalysis? AB - Alkyl amphetamine isomers (amphetamine, 1-phenyl-2-butylamine (PBA), methamphetamine, N-methyl-PBA, N,N-dimethylamphetamine, N-ethylamphetamine, N ethyl-PBA and N,N-diethylamphetamine) were purchased or synthesized and tested by immunoassay and GC/MS for their detectability in urine. Some cross reactivity was observed with PBA, N-methyl-PBA N-ethylamphetamine, and N-ethyl-PBA when analyzed using a series of commercial amphetamine and methamphetamine immunoassays. Chromatographic co-elution problems were observed for the underivatized isomeric group N,N-dimethylamphetamine, N-ethylamphetamine, and N-methyl-PBA under GC/MS conditions used; and their GC/MS spectra were quite similar. Of the potential derivatives, pentafluoropropionyl (PFP) anhydride and heptafluorobutyryl (HFB) anhydride provided adequate separation and easily distinguishable spectra using the electron-impact GC/MS conditions specified. PMID- 1748354 TI - Postmortem magnetic resonance images of the injured brain: effective evidence in the courtroom. AB - Magnetic resonance images (MRI) of the whole, formalin-fixed brain produce details of pathologic changes deep within brain substance not apparent on external examination. Photographs of these radiographic images present pathologic features in a black-and-white, 2-dimensional format which has proven particularly effective in court before judge and jury. This pathologist has noted acceptance of such photographs in explaining to jurors the details of his testimony in selected cases where brain trauma resulted in a wrongful death. Penetrating missile wounds and blunt impact injuries are particularly well documented by this method. PMID- 1748355 TI - Transferrin subtyping of bloodstains and semen using isoelectric focusing and immunoblotting. AB - Transferrin (TF) subtyping was carried out on bloodstains that had been made on cotton sheeting and stored under a variety of conditions ranging from -20 degrees C to +37 degrees C. The time limit of detection was longer than 54 weeks after dry storage under each condition. Moreover the correlation between isoprotein types of the TF in blood and semen samples from the same individual was determined in 103 men. All three TF common types and two rare types in all semen samples correlated with the type found in the corresponding blood sample. A combination of isoelectric focusing separation and immuno-enzyme-linked detection may prove to be very useful for forensic TF subtyping. PMID- 1748356 TI - Application of automatic image analysis (IBAS system) to age calculation. Efficiency in the analysis of several teeth from a single subject. AB - In a previous paper (M. Lopez-Nicolas et al., Forensic Sci. Int., 45 (1990) 143 150) we obtained a model of multiple regression to estimate age using computerized image analysis (IBAS) to study teeth. This method should provide more precise measurements of the parameters involved and to test this hypothesis we have carried out a blind study using more than one tooth from the same individual in order to check the diagnostic accuracy of the method. Our results show that individual variability introduced serious errors in tooth age estimation using computerized image analysis. However the study of more than one tooth per individual improves the accuracy of age estimation. Specific cases should therefore be interpreted cautiously, as a degree of variability can be expected using the parameters defined in this method. PMID- 1748357 TI - Estimation of stature from foot and shoe measurements by multiplication factors: a revised attempt. AB - Estimation of stature from foot and shoe measurements using multiplication factors is well known. It is a simple method and it is used very frequently as a ready reckoner in forensic anthropology. However the individual error is quite large. In the present work an attempt has been made to evolve revised multiplication factors to reduce this error so that this method (multiplication factor) can be used more effectively with smaller error. PMID- 1748358 TI - The ageing of bruises: a review and study of the colour changes with time. AB - This work was inspired by a recent case of child abuse where the question of the age of the bruises on the body was raised. The first part of this paper reviews published work on bruises. It illustrates the paucity of work in this field and the absence of studies of the colour changes in bruises of human skin with time. The second part of this paper consists of our own study of the appearance of bruises. The aim was to identify the colour changes which occur in bruises and over what time-scale, in order to determine whether bruises can be aged by appearance. A total of 369 photographs were obtained of bruises aged less than 6 h and up to 21 days old, in 89 subjects aged 10-100 years. It was found that the development of a yellow colour was the most significant change (subjects aged less than 65, P less than 0.001; subjects aged greater than or equal to 65 years, P less than 0.001). The development of a yellow colour occurred significantly faster in subjects aged less than 65 years. (P less than 0.001). The appearance of a blue and purple/black colour was of lesser significance. The appearance of a red colour did not alter significantly with time. From this study it was only possible to conclude that a bruise with a yellow colour was more than 18 h old. PMID- 1748359 TI - Positive and negative ion mass spectrometry and rapid isolation with Sep-Pak C18 cartridges of ten local anaesthetics. AB - The positive ion electron impact (PIEI), positive ion chemical ionization (PICI) and negative ion chemical ionization (NICI) mass spectra and a rapid isolation procedure using Sep-Pak C18 cartridges are presented for ten local anaesthetics. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m/z 86 due to the diethylaminoethyl or propylaminoethyl group constituted base peaks in six compounds. In the PICI mode, peaks due to M + H and M + C2H5 appeared. The cation at m/z 86 was also observed for the six compounds. This ion seems useful for the screening of local anaesthetics. In the NICI mode, anions at m/z M - H constituted base peaks for all compounds, peaks at m/z M + 12 appeared in many compounds. The total ion current in the PIEI and PICI modes generally gave higher sensitivity than in the NICI mode. Local anaesthetics present in whole blood or cerebrospinal fluid (CSF) could be rapidly isolated by use of Sep-Pak C18 cartridges with chloroform/methanol as an elution solvent. Their detection was possible using wide-bore capillary gas chromatography with SPB-1 and HP-17 wide-bore capillary columns with satisfactory separation from impurities. PMID- 1748360 TI - High performance liquid chromatographic determination of alcohols with reference to body distribution of methanol. AB - A method has been developed on reverse phase high performance liquid chromatography for simultaneous determination of methyl, ethyl and isopropyl alcohols under refractive index detection using pure water as the mobile phase. A good separation has been achieved between these alcohols. Detector response was linear with a detection limit of 5 mg/100 ml. Recovery studies were performed by adding known amounts of methyl and ethyl alcohols to blood, lung and liver within the range 80-90%. The reproducibility of the results was always greater than 90%. The quantitative distribution of methyl alcohol in postmortem body tissues and fluids has been reported in three cases of poisoning. PMID- 1748361 TI - Bloodgroup simulating activity in aerobic gram-negative oral bacteria cultured from fresh corpses. AB - The gram-negative aerobic oral bacterial flora of 100 consecutive corpses was isolated. After the identification and culturing of the isolated organisms, blood grouping was performed by the haemagglutination inhibition technique on dried culture smears, the dried culture medium and a dried ethanol extract of the bacteria. Forty-seven of the samples showed a gram-negative aerobic bacterial growth, giving 58 microorganisms of 14 different species. Positive blood grouping results were found in two of them (Escherichia coli and Serratia marcescens), both of type B. It is concluded that occasional mistyping of blood groups on saliva and oral material may be caused by the oral gram-negative aerobic flora, especially if the specimens are contaminated or putrefying. PMID- 1748362 TI - Enhanced genotoxicity by melphalan and hyperthermia in chronic heroin addicts. AB - Spontaneous melphalan- (MEL-) and MEL-hyperthermia- (MEL-HYP-) induced sister chromatid exchange (SCE) frequencies have been studied in 12 chronic heroin addicts (HER AD) and in 12 age- and sex-matched healthy controls. The incidence of spontaneous SCEs in lymphocytes from the HER AD was significantly greater (P less than 0.001) than those from the control subjects. When exposed to MEL in vitro, cells from both groups showed an increase in SCE frequency with yields from HER AD higher than those from controls. When exposed to MEL and hyperthermia (41.5 degrees C for 3 h) in vitro, cells from both groups showed further increases in SCE frequency with yields from HER AD higher than those from controls. We observed that hyperthermia (HYP) in combination with MEL synergistically enhances SCEs and cell division delays in both groups, with the synergistic effects in cells from HER AD higher than those from controls. PMID- 1748363 TI - ABO bloodgrouping on tooth material. AB - The ABO bloodgroup was determined on the pulp, dentin and enamel of 35 teeth using the adsorption-elution technique. A bloodstained compress from the extraction wound was used as the reference sample. Twenty teeth were examined within 6 weeks after extraction and fifteen teeth were examined 6-10 months after extraction. It was found, that bloodgrouping on pulp gives fairly good results, whereas the possibilities for correct bloodgrouping seem to be limited for dentin and debatable for enamel. Similar results were found in both groups of teeth. PMID- 1748364 TI - [Cancer and cytokines]. PMID- 1748365 TI - Psychosomatic approach to patients with gynecologic cancer. AB - In patients with terminal cancer, there is a need for a psychosomatic approach in which both the patient's psychological state, including QOL, and physical condition are considered. We studied patients with gynecologic cancer with the following practical objectives: 1. To evaluate the effect of a psychosomatic approach to patients with terminal gynecologic cancer; 2. Using psychological tests and interviews, to clarify the character tendencies of cancer patients, which are often reported in other countries; and 3. To discuss the benefits in the patient's attitude toward living with cancer. In case studies, separation anxiety of terminal cancer patients is increased due to impending death, and often patients cannot deal with these feelings. When the medical staff accepts these emotions, the patients' feelings even in the face of death often change to positive feelings of gratitude to the people around them. All of the results of psychological testing showed model answers, close to the mean of the normal range. This suggests that the patients were suppressing emotions behind their standard responses. Patients with uterine cancer showed a type C or cancer character, while those with ovarian cancer showed type A or heart disease character. Results indicated different attitudes between patients with uterine cancer and those with ovarian cancer. Cancer patients with a vigorous attitude (high POMS-V score pattern behavior) tended to have a good prognosis. This investigation represents a pilot study of a psychosomatic approach to cancer patients. However, recent psychoneuroimmunologic studies have reported the influence of emotion on cancer. Further studies of this kind are needed. PMID- 1748366 TI - [Clinical study on bronchial hyperresponsiveness and development of bronchial asthma in patients with persistent cough]. AB - The purpose of this study was to ascertain whether in patients with persistent cough the presence of bronchial hyperresponsiveness (BH) and development of asthma could be speculated based on clinical data. Only patients who met strict criteria excluding exogenous factors that influence BH, especially smoking or respiratory infection, were included in this study. The study group included 15 males and 50 females aged 18 to 62 years (mean +/- S.D. of 44 +/- 12 years) whose physical findings, chest X-rays, spirometry results and peripheral leukocyte counts were within normal limits. Duration of cough was at least one month. The patients had no history of wheezing, dyspnea or previous bronchodilator therapy. None of them had ever been smokers. In addition, there was no history of upper respiratory tract infection in the preceding month. BH was assessed by "Astograph" using methacholine. Cmin and Dmir or SGrs/Grs cont. were measured as the indexes of bronchial sensitivity or reactivity respectively. A methacholine Cmin of 3, 125 micrograms/ml or less was taken as a positive indication of BH. The evaluated clinical data were age, pulmonary function (spirogram or flow volume curve), atopic factors (serum total IgE and family or personal history of atopic diseases), peripheral eosinophil count, bronchial sensitivity or reactivity, and clinical features of cough (induction by exercise or cold air and nocturnal worsening). The results were as follows. (1) Twenty-nine (45%) of 65 patients were BH-positive (BH-positive group). (2) There was no significant difference in age, %FVC, IgE, and family or personal history of atopic diseases between the BH-positive and negative group. However, the BH-positive group had significantly lower FEV1.0%, %FEV1.0, PEFR, (p less than 0.05) and V25/H (p less than 0.01) and a higher peripheral eosinophil count (p less than 0.05) than the BH-negative group. (3) Seventeen (85%) of 20 BH-positive patients prescribed bronchodilators (beta 2 agonist/theophylline) responded to therapy within a month. (4) Seven (29%) of 24 BH-positive patients available for 2 years follow-up developed clinical asthma. (5) There was no significant difference in %FVC, FEV1.0%, V25/H and peripheral eosinophil count between the patients who developed asthma (Group A) and those who did not (Group N-A). However, The patients in Group A were older than those in Group N-A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1748367 TI - [Positron emission tomography (PET) before and after treatment of hyperammonemia in a patient with decompensated liver cirrhosis]. AB - A 56 year-old-male liver cirrhosis patient was admitted because of hepatic encephalopathy with hyperammonemia. We measured cerebral blood flow (CBF), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate for oxygen (CMRO2) by using PET before and after treatment of hyperammonemia. At the time of the first PET, serum ammonia was 152 micrograms/dl and on the second PET it was 88 micrograms/dl. The electroencephalogram and number connection test also improved on the second PET. CBF and CMRO2 were decreased by 25-42% in comparison to normal control and OEF increased 1-24% at first examination. Similar abnormal reduction of both CBF and CMRO2 and increase of OEF were seen at second examination. Reduced CBF and CMRO2 regardless of serum ammonia level suggests that heptic encephalopathy may be, at least in part, associated with pathological changes in brain tissue induced by hepatic metabolic disorder. PMID- 1748368 TI - [A case of liver cirrhosis associated with chronic subdural hematoma and hepatic encephalopathy]. AB - A 58-year-old male liver cirrhosis patient, who had a history of recurrent hepatic encephalopathy, was admitted to our hospital because of clouding of consciousness. He had an episode of recent head trauma. On admission, he was drowsy and exhibited flapping tremor, fetor hepaticus and ascites. Laboratory data showed an increase in blood ammonia level, and a decrease in peripheral thrombocytes, serum albumin and prothrombin value. A ratio of branched-chain to aromatic amino acids was reduced. Antibody against hepatitis C virus was positive. His electroencephalogram showed bilaterally large synchronous slow waves. He was treated with intravenous branched-chain amino acids, and recovered. Cranial computed tomography on day 9 demonstrated a crescent shaped area of low density in the right frontotempoparietal subdural region. He was diagnosed as chronic subdural hematoma, which was treated surgically. It has been suggested that chronic subdural hematomas develop as a complication of hemostatic deficiency due to liver cirrhosis. PMID- 1748369 TI - [Development process of human fetal movement--special reference to REM sleep/NREM sleep/arousal condition]. PMID- 1748370 TI - [Isosorbide dinitrate ameliorates myocardial ischemia after development of collateral function in a canine model]. AB - The effects of i.v. administered isosorbide dinitrate (ISDN) on the reduced level of regional myocardial function during coronary occlusion were studied in conscious dogs before and after collateral development and in the absence of persistent coronary stenosis. The animals were instrumented during sterile surgery with a miniature pressure gauge for measuring left ventricular pressure and a cannula for aortic pressure. Two pairs of piezoelectric crystals were placed in normal and ischemic areas to determine regional circumferential length. A hydraulic cuff occluder and a Doppler flow probe were placed around the left circumflex coronary artery. Collaterals were induced to develop by 2 min of coronary occlusion applied repetitively at an interval of 32 min for 2 to 9 days, until the regional dysfunction produced by coronary occlusion had disappeared. Collateral development was estimated according to percentage of systolic shortening and endsystolic length area (ESL area) during the occlusion. Before collateral development, ISDN in a dose of 100 micrograms/kg did not affect the level of regional dysfunction. The ESL area was 250 +/- 54 and 248 +/- 52 mm.sec before and after ISDN, respectively. After collateral development, the ESL area was 51 +/- 13 mm.sec and it decreased by 35% after the i.v. administration of ISDN. The improvement by ISDN of transient myocardial dysfunction was achieved even during electrical tachypacing. Accordingly, the beneficial effects of ISDN on regional wall motion rendered ischemic during transient coronary occlusion were appreciable after coronary collateral development. PMID- 1748371 TI - A different view of queues in Ontario. PMID- 1748372 TI - Health care in Australia: lessons from down under. PMID- 1748373 TI - The 1987 revision of physician fees in Germany. PMID- 1748374 TI - Europe after 1992: implications for pharmaceuticals. PMID- 1748375 TI - Translating the U.S. HMO experience to other health systems. PMID- 1748377 TI - Advancing the debate on international spending comparisons. PMID- 1748376 TI - International health spending: comparisons with the OECD. PMID- 1748378 TI - Health status in east European countries. PMID- 1748379 TI - Spain's citizens assess their health care system. PMID- 1748380 TI - Health care systems in twenty-four countries. PMID- 1748381 TI - Canadian/U.S. health care: reflections on the HIAA's analysis. PMID- 1748382 TI - Importing a model of hospital quality from The Netherlands. PMID- 1748383 TI - International health grant making. PMID- 1748384 TI - Health systems in three nations. PMID- 1748385 TI - Impact of expanding Medicaid. PMID- 1748386 TI - Medicaid and the working poor. PMID- 1748387 TI - States and the Medicaid debate. PMID- 1748388 TI - Future value of pharmaceuticals. PMID- 1748389 TI - European view of U.S. drug policy. PMID- 1748390 TI - Britain's health care experiment. PMID- 1748391 TI - Internal market reform of the British National Health Service. PMID- 1748392 TI - Reforming health care in seven European nations. PMID- 1748393 TI - Soviet health care from two perspectives. PMID- 1748394 TI - Japanese health care: low cost through regulated fees. PMID- 1748395 TI - A comparative study of proliferation-associated parameters in B-cell non-Hodgkin lymphoma. AB - The prognostic value of three proliferation-associated parameters, the frequency of cells in S-phase, mitotic index (MI) and serum deoxythymidine kinase levels (S TK), was examined in 106 primary cases of B-cell non-Hodgkin lymphomas (NHL), 76 'low grade' NHL and 30 'high grade' NHL and compared with morphology and clinical variables. All three proliferation factors displayed large differences in the mean values of the two groups 'low grade' and 'high grade' NHL, and all revealed significant prognostic information. In 'low grade' NHL, the information decreased with follow-up time. A correlation (r = 0.7) was noted between S-phase values and MI but not between S-TK and the two others. In the entire patient material and in the two prognostic groups defined by morphology, S-TK gave the best prognostic information. MI gave better prognostic information than S-phase values in the whole material and in 'low grade' NHL, whereas the reverse appeared to be true for 'high grade' NHL. In the multivariate analyses, no other parameter apart from S-TK provided any further prognostic importance in the cases of 'high grade' NHL, whereas in that of 'low grade' NHL, MI, stage, age and histology had independent importance. PMID- 1748396 TI - Treatment of terminal-phase chronic myelogenous leukemia with intermediate-dose cytarabine and hydroxyurea. AB - We used intermediate doses of Ara-C (IDAra-C) in the treatment of 15 patients with chronic myelogenous leukemia (CML) in blast crisis and, combined with hydroxyurea, in 20 CML patients in accelerated phase. Patients with blastic CML received intensive 5-day courses of IDAra-C 600 mg/m2 every 12 h as a 2-h infusion. Of 15 patients, three achieved complete response (CR) and three partial response (PR), for an overall response rate of 40 per cent. All patients developed severe leukopenia and thrombocytopenia, and two died in hypoplasia. Except nausea and vomiting requiring medication, other nonhematologic toxicities were uncommon. Median response duration was 4 months (range 1 to 7 months). Survival was 5 months for responders and 1.5 months for nonresponders. Patients with CML in accelerated phase were treated with two-day courses of IDAra-C 600 mg/m2 every 12 h by 2-h infusion, every two-three weeks. Daily hydroxyurea 1-1.5 g/day was administered between courses. Of 20 patients, 15 (75 per cent) achieved a good PR with rapid improvement of the symptoms of disease acceleration. The median duration of response was 11 months (range 3 to 38 months); duration was over 24 months in five patients. The median survival from the start of IDAra-C was 13 months for responders and 3.5 months for nonresponders. We conclude that IDAra-C is an effective approach for CML in terminal phase. Its use in 5-day induction courses for blast crisis CML has a response rate comparable to that achieved with high-dose Ara-C. In patients in accelerated phase, the combination of short courses of IDAra-C with hydroxyurea is a well-tolerated treatment able to improve substantially the clinical and hematologic symptoms of disease progression. PMID- 1748397 TI - Increased levels of circulating interleukin-6 in patients with Hodgkin's disease. AB - Expression of interleukin-6 (IL-6) and IL-6 receptors has been demonstrated in Hodgkin and Reed-Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL-6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL-6 was only rarely detectable in healthy controls or patients with non-Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL-6 levels (range 12-32 pg/ml). The rates of detectable IL-6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B-symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL-6-negative and IL-6-positive patients. Except in one of 23 follow up sera taken after therapy, IL-6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL-6. PMID- 1748398 TI - A pilot study of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL). AB - In a pilot study of the combination of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL), 10 patients with advanced or progressive disease were treated in four centres. Up to a total of 15 courses in individual patients were given. Toxicity was relatively mild with nausea due to epirubicin being the most commonly reported side-effect. One patient developed a probable septicemia during a period of neutropenia. In another patient who died from probable Pneumocystis carinii pneumonia (PCP) after only one course of therapy, death could not be regarded as necessarily treatment-related. In seven previously untreated patients, one complete response and four partial remissions were seen. All three previously treated patients showed partial remissions. PMID- 1748399 TI - Quantitative study of KI-67 antibody staining in 46 T-cell malignant lymphomas using image analysis. AB - Image analysis with a SAMBA 2005 (ALCATEL-TITN, Co) was used to quantify the Ki 67 stained area percentage in 46 T-cell malignant lymphomas (T-ML), classified according to the updated Kiel classification. This parameter demonstrated correlation with the number of Ki-67-positive cellular profiles (r = 0.88, P less than 0.001) and was more reproducible than cell counting. A significant difference was found between low and high grade T-ML (mean values +/- SEM respectively of 10.20 +/- 1.82 per cent and 25.63 +/- 3.15 per cent). The most interesting findings were that: (1) AILD-type T-ML showed an intermediate proliferation rate (15.55 +/- 2.72 per cent) between pleomorphic T-ML with medium and with large cells (respectively 12.53 +/- 3.64 per cent and 22.43 +/- 3.46 per cent), both of which belong to the high grade malignancy group. This finding is in accordance with the poor prognosis of this subtype despite its classification in the low grade malignancy group. (2) Subclassification of the pleomorphic MLs according to the predominance of small, medium or large cells, demonstrated significant differences between these three subtypes. However, the great overlap of values between pleomorphic T-ML with medium and with large cells, seems to indicate that the subclassification of these two subtypes is less valid. (3) A wide range of values with overlap was observed in AILD-type ML, in pleomorphic with medium or large cells and in lymphoblastic T-ML: for these T-ML with variable survival courses, the Ki-67 area percentage, one parameter of proliferative activity, appears worth studying as a prognostic factor. PMID- 1748400 TI - Recombinant human granulocyte macrophage colony stimulating factor following alternating non cross resistant chemotherapy in Hodgkin's disease. AB - Fourteen patients with Hodgkin's disease (two previously untreated, 12 following relapse or with refractory disease) were treated with a combination chemotherapy regimen comprising chlorambucil, vinblastine, procarbazine, prednisolone, etoposide, vincristine and adriamycin administered on days 1-8. Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (mammalian glycosylated, Sandoz/Schering-Plough) was administered after alternate cycles of chemotherapy from day 10 for 7 days by continuous intravenous (i.v.) infusion in 12 patients in a dose finding study (dose: 2 micrograms/kg/day in four patients, 4 micrograms/kg/day in four patients and 8 micrograms/kg/day in four patients) and by daily subcutaneous (s/c) injections in two patients (8 micrograms/kg/day). There was a rapid peripheral leucocytosis following the rhGM-CSF, reaching a peak at 1-2 days in 12/14 patients. The initial leucocytosis was composed of neutrophils followed by a rise in immature myeloid cells. There was no difference observed in the duration or depth of the nadir following chemotherapy or in the rate of recovery of peripheral white cell counts between cycles with and without rhGM-CSF in patients treated with 2 and 4 micrograms/kg/day. At the dose of 8 micrograms/kg/day, 3/6 patients had a shorter nadir duration in the cycle with rhGM-CSF, compared with cycle without rhGM-CSF. There was no difference in frequency of infection in cycles with and without rhGM-CSF. Following chemotherapy, six patients achieved clinical remission, six partial remission and two had progressive disease. PMID- 1748401 TI - [Study of enamel caries-lesion produced by artificial plaque]. AB - The authors used the cariogenic bacteria isolated from human dental plaque to produce an artificial plaque which can produce carious lesion in vitro. Lesions on human enamel slabs produced by artificial plaque and single bacterium were observed under polarized light microscope and scanning electron microscope. The results showed that the characters of artificial carious lesions are very similar to natural enamel caries. It is very difficult to differentiate them under the microscopes. Compared with the lesions produced by single strain, the destructive fashion observed in lesions produced by artificial plaque is more similar to the changes produced by natural dental plaque. PMID- 1748402 TI - [The effect of plaque fluid on demineralization of enamel powder]. AB - The aim of this study was to explore any substance in dental plaque which might affect the demineralization of enamel. Plaque fluid was prepared by centrifugation of pooled plaque from 56 young adults without periodontal diseases. Enamel was separated from healthy teeth of adolescents and crushed into powder. The enamel powder was treated separately by plaque fluid and synthetic plaque fluid (as a control, with similar calcium, fluoride content and pH as the natural). After this, the enamel powder was washed with PBS. Both the plaque fluid-treated and synthetic plaque fluid-treated enamel powder were demineralized by mixed organic acid (pH 4.5). The calcium content in both plaque fluids, PBS and organic acid after treatment with enamel powder was analysed by atomic absorption spectrophotometer. The results showed that there was no promoting effect in plaque fluid on demineralization of enamel, but, on the other hand, some protecting action was observed which might contribute to the presence of proteins in plaque fluid. PMID- 1748403 TI - [The distribution of apolipoproteins AI, CII and CIII mRNA in rat tissues]. AB - It was demonstrated that apo AI, CII and CIII mRNA were distributed in rat (Sprague Dawley) liver, intestine, brain and kidney by RNA-dot blot analysis with apoAI, CII and CIII cDNA probes. The relative abundances of apoAI in liver, intestine, brain and kidney tissues are 100%, 212%, 170% and 224%, respectively, those of apoCII are 100%, 61%, 163% and 214%; and those of apoCIII 100%, 65%, 70% and 73%, respectively. The experiment was repeated for three times. The results were discussed in this paper. PMID- 1748404 TI - [Preparation of SOKT1-RTA immunotoxin and its specific cytotoxic effect on human T lymphocytes]. AB - An immunotoxin, SOKT1-RTA, was prepared successfully by conjugating a murine anti human T lymphocyte monoclonal antibody (McAb) SOKT1 and the ricin toxin A chain (RTA) with the heterobifunctional linker SPDP. At the presence of 20 mmol/L NH4Cl, the SOKT1-RTA conjugate killed 82% of the human peripheral blood T cells (PBT), and decreased their 3H-Leu incorporation to 6.2% of the untreated controls. The toxic effect of the immunotoxin can be partially blocked by unconjugated SOKT1, but not by an irrelevant McAb D51. These results indicated that the SOKT1-RTA conjugate still retains both functions of its component parts:binding to human PBT specifically, and inhibiting protein synthesis. It may be an effective reagent for in vitro depletion of immunocompetent T cells from human bone marrows. PMID- 1748405 TI - [Construction of gene bank of L. interrogans serovar lai and cloning of homological sequences of virulent leptospirosis]. AB - A gene bank of the main pathogen of pulmonary diffuse haemorrhage type leptospirosis (PDH), L. interrogans serovar lai strain 017, was first constructed with plasmid vector pUC9, which contained 610 recombinant clones and laid the foundation for further investigation of molecular characteristics of leptospires with strong virulence. Recombinant plasmids which have homological sequences of pathogenic leptospires were screened from the gene bank. A recombinant plasmid, designated pCX7, could detect 1.7 kb fragment of strain 017, 9.0 kb of strain 601 and 30.0 kb of strain 610 respectively without cross hybridization with nonvirulent leptospires such as L. biflexa strain Patoc I and Leptonema illini. pCX9, another recombinant plasmid, could detect 1.9 kb fragment of strain 017 and had no hybridization with other pathogenic or nonpathogenic leptospires. The results showed that the degree of homology between pathogenic and non-pathogenic leptospires was very low and the degree of homology was very high among the pathogenic leptospires. PMID- 1748406 TI - [Plasma PGI2 and TXA2 levels on a model of PDH in leptospirosis]. AB - Guinea pigs were intravenously injected with icterhemorrhagiae serogroup Lai serovar strain 017 leptospirosis to model the pulmonary diffuse hemorrhage (PDH) in leptospirosis. Thirty-eight hours after the injection, the jugular arteries were catheterized to collect blood sample. The plasma was prepared for radioimmunoassay of TXB2 and 6-keto-PGF1a, the stable metabolites of TXA2 and PGI2 respectively. The plasma level of TXB2 in the experimental group, 107.15 +/- 41.65 pg/ml (n = 7), almost doubled that of the control, 54.05 +/- 12.93 pg/ml (n = 7), with significant difference (P less than 0.01); meanwhile, no significant difference was observed of 6-keto-PGF1a, 67.97 +/- 16.89 pg/ml (n = 6) vs. 98.06 +/- 40.63 pg/ml (n = 9) with P greater than 0.1. The fact that TXA2 causes vasoconstriction and increases vessel permeability suggests that TXA2 elevation should play a role in the mechanism of PDH in leptospirosis. PMID- 1748407 TI - [Isolation of desmosomes: a marker for epithelial tumors]. AB - A simple method is reported for the isolation of desmosomes. The fresh noncornified layers of cow nose epidermis were immersed in 0.1 mol/L citric acid sodium citrate buffer (pH 2.3, containing 0.5 mmol/L PMSF), and then treated with homogenization and discontinuous sucrose density gradient centrifugation. Desmosomes were located at the 50-56% sucrose interface. Electron microscopy revealed that the characteristic desmosome structure was well preserved, and that a few intermediate filament bundles attached to desmosome plaque were removed by the solubilizing action of the buffer. Approximate 100 mg desmosomes (dry weight) were got from 20g wet noncornified layers of epidermic tissue. PMID- 1748408 TI - [Chemiluminescent immunoassay for insulin]. AB - In this paper is reported solid phase chemiluminescent immunoassay for insulin with N-(4-aminobutyl)-N-ethylisoluminol (ABE1) labelled antibody and a double antibodies sandwich procedure. ABEI-CoCl2-H2O2 was used as the chemiluminescent system and the linear range of insulin was 0.3-150 microU/tube. The correlation coefficient of the log-log regression equation was 0.985 and the absolute limit of detection 0.32 microU/tube. PMID- 1748409 TI - [The qualitative and quantitative analyses of protein with a novel fluorescence agent (EPQS) by fluorescent scanning on solid substrate]. AB - We synthesized a new fluorescence agent, EPQS, which could be soluble in water and was stable in the analytical process. It was characteristic of good fluorescence parameters. Human serum albumin (HSA) was marked with EPQS and purified by the paper electrophoresis dialysis. We determined the fluorescent spectra and excitation spectra of the marked HSA, or EPQS on the cellulose acetate paper by RF-510 fluorescence spectrophotometer-thin-layer chromatoscanner. The former lambda ex = 370nm lambda em = 470nm; the latter lambda ex = 382nm lambda em = 476 nm. Then we touched different quantity of EPQS HSA upon the cellulose acetate. The fluorescent scanning on the paper disclosed that the relationship between the quantity adopted and the fluorescence intensity is linear. These showed that the protein could be quickly determined qualitatively and quantitatively by this simple method, and EPQS was useful. PMID- 1748410 TI - [Determination of hydrocortisone and methylprednisolone in plasma by reversed phase HPLC]. AB - A sensitive and rapid method for the simultaneous measurement of both hydrocortisone (HC) and methylprednisolone (MP) using dexamethasone (DX) as the internal standard was presented. High-performance liquid chromatograph Model 344 (Beckman, USA) with a 254 nm wavelength UV detector and reversed-phase Ultrasphere ODS (5 microns) column was used. Sample was extracted with ethyl acetate and the organic layer was evaporated to dryness under an air stream in a 37 degrees C water bath. The residue was dissolved in 30 microliters mobile phase and 20 microliters injected. The mobile phase of methanol and 0.01 mol/L acetate buffer (pH 3.0) (64:36) was pumped at 1.0 ml/min through the column. The detector was operated at 0.005 aufs. The retention time for HC, MP and DX was 5.43 min, 7.7 min and 11.5 min, respectively. Standard curve was linear in the concentration range of 0.02 to 1.28 mg/L for HC and 0.05 to 12.8 mg/L for MP. Sensitivity was 1 ng for HC and 1.5 ng for MP; extraction recovery 76-83%; within day CV less than 4%, and inter-day CV less than 6% for both steroids. PMID- 1748411 TI - [Analysis of outer membrane proteins from eight strains of Campylobacter in SDS PAGE]. AB - The outer membrane proteins (OMPs) from 8 strains of Campylobacter, including 5 reference strains and 3 local strains, were isolated and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that the population distributions of molecular weight of OMPs from different species and sources were alike based on the Rank Sum Test analysis. The number of bands of major OMP was around 2-3, the molecular weight of which varied from 33 68 kd. Moreover, three C. jejuni local strains isolated from patients in China showed common characteristics of OMPs to the reference strains. It is suggested that the OMPs of Campylobacter are of a conservative and stable structure. PMID- 1748412 TI - [The influence of vagotomy on stomach endocrine cells in rat]. AB - The effects of unilateral truncal vagotomy (UTV) and bilateral truncal vagotomy (BTV) on antrum EC cells, G cells and oxyntic gland area argyrophil cells were studied in rats by using immunohistochemistry processes, Grimelius argyrophil stain and microscopic image analysis technique. RESULTS: (1) In UTV animals, two weeks postoperation, the sectional areas of EC cells were significantly smaller in denervated side than In the other side (17%, P less than 0.05). In the innervated side of antrum, the sectional areas of EC cells were larger than those in controls (13.5%, P less than 0.05). But, five weeks after UTV, the size of EC cells was not significantly different in all animals. These suggest that vagal denervation can inhibit relatively the functional activity in a short period, but this inhibition could be compensated later. (2) There were no morphological changes in G cells of UTV rats. In BTV animals, the quantity of G cells in antrum increased by 36.2% (P less than 0.05) and their sectional areas were larger than those in sham by 26.2% (P less than 0.05). These indicate that the function of G cells is more active in BTV animals and the functional change of G cells is related to the pH value of gastric juice. (3) In UTV rats, the oxyntic gland area argyrophil cells (ECL cells are dominant) were significantly reduced in two weeks (26.8%, P less than 0.01) and in five weeks (20.1%, P less than 0.05) in denervated side after UTV. The cells became smaller also. These suggest that vagus can influence the function, proliferation and growth of ECL cells. PMID- 1748413 TI - [Prophylactic effect of refined amorphophallus konjac on MNNG-induced lung cancers in mice]. AB - Three hundred and seventy LACA mice of seven weeks old were used in 2 batches for studying the prophylactic effect of Konjaku powder on MNNG-induced lung cancers. These mice (within each batch) were randomly allocated to four groups, namely positive control (MNNG), refined Amorphophallus Konjac (R.A.K.), complex (MNNG + R.A.K.), and blank control (C). In MNNG group, MNNG (250 micrograms) was injected intravenously once five days for seven times in each mouse, the total dosage of MNNG was 1.75 mg. In R.A.K. group, according to w/w, 8% R.A.K. was well mixed into 92% common diet for long-term term breeding. In complex group, MNNG was given as that in MNNG group and the mice were reared as those in R.A.K. group. The mice in MNNG group and in C group were all reared by common diet. The results of experiments showed different degrees of preventive effect of R.A.K. on MNNG induced lung cancers in LACA mice. R.A.K. not only exerted effect on the number of induced cancer, causing a drop of the cancerous rate from 79.75% to 20.00% and the mean number of cancer in each animal, but also prolonged the survival time of animals. At the same time, the constituent ratio of the kinds of tumor denoted a decrease in malignancy (adenoma with malignant change), an absence of adenocarcinoma and relative increase in benign adenoma. The results of experiments also exhibited good duplication as well as absence of adverse reactions to Konjaku powder. PMID- 1748414 TI - [Transplacental passage of vanadium after treatment with vanadium pentoxide in Wistar rat]. AB - The passage of vanadium pentoxide across the placenta into the embryo/fetus was investigated by analyzing the vanadium content in embryo/fetus at various intervals between 1 h and 48 h after treatment of pregnant Wistar rats with single dose of the V2O5 (5mg/kg) on days 16-18 of gestation, at 4h after treatment of pregnant rats with single dose of V2O5 (5mg/kg) on day 12, and at 120 h after treatment of pregnant rats with dose of V2O5 0.33, 1.0, 3.0 mg/kg on days 6 through 15. The V concentration was determined by catalytic polarography. At after treatment on day 12, the V concentrations in maternal blood, placenta and embryos were elevated in comparison with those of the untreated group. At 4 48 h after treatment on days 16-18, the V concentrations in placenta and fetuses were elevated in comparison with those of the untreated group. The V concentration at 4 h after treatment in various tissues is the highest one among different time points. On days 16-18, 4 h after treatment, the V concentration in placenta was elevated in comparison with that on day 12 of gestation, but the V concentration in embryo/fetus was decreased. At 120 h after treatment on days 6 15, the V concentration in fetus is still high in comparison with that of the untreated group. The V content of fetus varied according to doses, suggesting that embryo/fetus accumulates vanadium. The results showed that vanadium can pass through the placental barrier and enter the embryo/fetus during the embryonal organogenesis in rat, but placenta accumulates vanadium, and the barrier action increases with placental maturity. PMID- 1748415 TI - [Applied anatomy of lymph drainage of lower lip mucosa]. AB - The lymph drainage of lower lip mucosa was studied in 30 fresh cadavers of fetus and neonatus by submucosa injection of 30% Prussian blue of chloroform solution. The collecting lymphatics in lateral third of both the right and left sides of the lower lip mucosa ran laterally to the angles of the mouth, and then back- and downward between mandible and depressor muscle of angle of mouth, and finally, accompanying the facial vessels, emptied into submandibular lymph nodes. The efferent lymphatics of the latter emptied into angular lymph nodes and jugulo omohyoid lymph nodes. The collecting lymphatics in the middle third of the lower lip mucosa went superficially to the mental muscle and downward into submental lymph nodes. The efferent lymphatic of the latter emptied, anteriorly to the body of the hyoid bone, latter- and downward into right and left jugulo-omohyoid lymph nodes. All collecting lymphatics lie in the loose connective tissue between the muscles. PMID- 1748416 TI - [The relationship between hepatitis B and renin-angiotensin-aldosterone system]. AB - The angiotensin II (AT II) levels in plasma were measured 68 times by using radio immunoassay in 30 patients with viral hepatitis B (HB) and in 35 healthy persons as the control group. The results showed that the AT II levels of patients with HB were much higher than those of the control group (P less than 0.001). They were 219.25 +/- 91.31 ng/L and 60.70 +/- 10.73 ng/L, respectively. These indicated that the renin-angiotensin-aldosterone system (RAAS) of the patients was in exciting state. The levels of 8 cases of severe chronic active hepatitis (SCAH) (AT II = 270.40 +/- 106.55 ng/L, 6 cases of subacute fulminant hepatitis (SFH) (AT II = 332.80 +/- 140.12 ng/L), and 4 cases of hepatocirrhosis (HC) (AT II = 218.50 +/- 97.64 pg/ml) were all higher than those of 8 cases of chronic active hepatitis (CAH) (100.50 +/- 83.81 ng/L) and those of 4 cases of acute icteric hepatitis (A1H) (123.33 +/- 64.97 ng/L). These findings showed that the levels of AT II were directly related with the severity of the illness. The AT II levels of 8 cases of HRS (270.50 +/- 66.31 ng/L) were higher that those without HRS (174.50 +/- 78.48 ng/L). After treatment with captopril (CPT), the renal function of the patients returned to normal and the patients got better, while the AT II levels decreased greatly. The results suggested that high AT II levels in plasma may be one of the causes aggressing the HRS. The CPT may inhibit the produce of AT II and there are some therapeutic effects for the HRS. PMID- 1748417 TI - [Clinical value of the Chengdu classification of non-Hodgkin's lymphomas]. AB - Two hundred forty-nine cases of non-Hodgkin's lymphomas (NHL) were reviewed by using the working classification of NHL (Chengdu, 1985). The results showed that the patients of 249 cases of NHL ranging in age from 5 to 76 years, with the mean age of 42 of the types were separated into three major prognostic groupings as follows: 1. low (41 of 249 cases, small lymphocytic 27 cases, lymphoplasmacytoid 2 cases, follicular cleaved 7 cases, follicular cleaved and noncleaved 5 cases); 2. intermediate (58 of 249 cases, diffuse cleaved 28 cases, diffuse cleaved and noncleaved 27 cases, follicular noncleaved 3 cases); and 3. high grade malignancy (150 of 249 cases, diffuse noncleaved 49 cases, lymphoblastic 41 cases, immunoblastic 13 cases, polymorphic 39 cases, clear cell 2 cases, histiocytic 6 cases). Each group was significantly different from the others (P less than 0.05). The prognosis of patients with angioimmunoblastic lymphadenopathy like T cell lymphoma (9 of 249 cases) was not more significant (P greater than 0.05) than that of patients with other polymorphic lymphoma (30 of 249 cases). The results showed this Chengdu classification of NHL is good for practice and usage in clinical evaluation and routine surgical pathology. PMID- 1748418 TI - [Investigation on high risk factors of neonatal necrotizing enterocolitis]. AB - In order to evaluate the factors in high-risk neonatal necrotizing enterocolitis (NEC) and predict the prognosis of NEC, a retrospective analysis of 32 factors was made in 42 neonates with NEC. The cases were divided into a low-risk (survival) group and a high-risk (death) group. Of 32 factors compared between these two group, eight were found to be of significance in evaluating the severity of NEC, and six of them were used in the development of a NEC scores (1) number of days before beginning of artificial feeding; (2) neonatal asphyxia or distress; (3) immature form in WBC differential; (4) CO2 combining power; (5) abdominal tenderness; (6) presence of portal vein air (PVA). All laboratory values and physical and radiographic signs were collected during initial presentation of NEC. Neonates with a score of 3 or more are at an increased risk of developing severe NEC with a 83% mortality. PMID- 1748419 TI - [Evaluation of a logistic regression model in predicting the prognosis of Graves' disease treated by antithyroid drugs]. AB - One hundred and twelve new cases of Graves' disease were treated by tapazole for 6 months and followed up for another 12 months. The initial dose was 30 mg/d. Clinical and biochemical euthyroidism was achieved within 1 to 3 months, then a maintenance was given until cessation of drugs at 6 months. One hundred and eleven cases completed the study. Remission and relapse were defined at the end of follow-up for 1 year according to the presence or absence of clinical manifestation of hyperthyroidism and the levels of T3 and T4. The results of the 12-month follow-up showed that 46 of 111 cases were in remission, and the remaining 65 cases suffered relapse. A logistic regression model with 4 variables was established, which included thyroid suppression rate and goitre size by palpation at the end of drug treatment, the level of T3 before therapy, and the patients' age. The model had 81.5% sensitivity, 84.8% specificity and 82.9% (92/111) accuracy in predicting the outcome of Graves' disease after withdrawal of drug for 1 year. The results were much better than any other univariate analysis in this study. PMID- 1748420 TI - [Application of polychotomous logistic regression in the study of risk factors predisposed to postpartum hemorrhage]. AB - To determine the role of history of induced abortion and pregnancy induced hypertension in postpartum hemorrhage, a polychotomous logistic regression method was introduced to analyze the data gathered in an investigation of blood loss among 933 parturients in some counties of Sichuan and Ningxia provinces. The results show that postpartum hemorrhage caused by placenta factors is related to a history of induced abortion and pregnancy induced hypertension with relative risks 2.55 (95% confidence interval = 1.2-5.3) and 4.94 (95% confidence interval = 1.8-13.2), respectively. An increased risk was noted for postpartum hemorrhage associated with pregnancy induced hypertension (relative risk = 2.58, 95% confidence interval = 1.3-5.2), but not with induced abortion. Suggestions were made for prevention of postpartum hemorrhage. PMID- 1748421 TI - [Intrauterine adhesion and ovulatory disorder following induced abortion]. AB - Follicular stimulating hormone, luteinizing hormone, prolactin, estradiol and progesterone were measured by radioimmunoassay in 34 patients with those from 34 normal cycling women after induced abortion. The result showed that the anovulatory incidence of the patients (20.6%) was significantly higher than that of the controls (2.8%) (P less than 0.05). Increased prolactin and premature ovarian failure might be responsible for the anovulatory disorder, resulting in unsatisfactory restoration of fertility. It is suggested that the low success rate in treating patients with intrauterine adhesion after induced abortion may be due to premature ovarian failure and hyperprolactinaemia. PMID- 1748422 TI - [Immunodiagnosis of ovarian cancer]. AB - Ovarian tumor associated antigen was isolated from human serous cystadenocarcinomas of ovary and purified by using affinity chromatography columns coupled to anti-normal female serum and anti-normal ovarian tissue gamma globulin. Antiserum was prepared from New Zealand white rabbits. The antiserum was absorbed with normal female serum and extracts of normal ovarian tissue thoroughly. The absorbed antiserum was appraised by immunodiffusion, immunoelectrophoresis and counter-immunoelectrophoresis with intensifiers. The absorbed antiserum has a specific immune precipitin with extracts of ovarian tumor tissue. Counter-immunoelectrophoresis with intensifiers was used to detect the ovarian tumor associated antigen in the tissue and serum of various patients. Twenty-eight of 40 ovarian tumor extracts and 1 of 5 cervical carcinoma extracts showed the presence of the cancer antigen. 14/40 were positive in the sera of ovarian tumor patients and 6/10 positive in the sera of ovarian serous cystadenocarcinoma patients; 1/5 positive in the sera of cervical carcinoma patients and 2/10 positive in the sera of ovarian cysts patients. No positive result for the sera of normal females was noted. The specificity, sensitivity and accuracy of the method were 94.7%, 42.3% and 83.3%, respectively. PMID- 1748423 TI - [Consecutive study of nutritional composition of milk from mothers of preterm delivery]. AB - The content of protein, fat, lactose, potassium, sodium, calcium, phosphorus, magnesium, copper, iron, zinc in preterm human milk was determined from the longitudinal samples during the first 8 weeks of lactation. Changes in content, over time were tested by analysis of variance. Protein, potassium, sodium, copper, iron, zinc content decreased significantly as lactation progressed. Based upon these data, a preterm infant fed 200 ml per kg per day of its own mother's milk would receive an excess of all substrates except calcium, phosphorus and iron over the estimated intrauterine accretion rates. Within 4 weeks the first in the postpartum period, the average intake of calcium, phosphorus, magnesium and copper was lower than the recommended intake. Iron intake is not adequate. After 4 weeks, the average intake of protein, sodium and zinc was lower than the recommended intake. The results may offer a basic datum for establishing premature infant feeding and formulation of human milk fortifiers (HMF). PMID- 1748424 TI - [Change of T lymphocyte subsets in peripherial blood of children with malnutrition and zinc deficiency]. AB - Sixty children with malnutrition were investigated in this study. The results showed a reduction of serum zinc in moderate and severe cases compared with the mild and normal groups. OKT3+, OKT4+ and OKT8+ cells in peripheral blood of mild malnutrition were significantly decreased in contrast to normal control. The reductive degree of OKT8+ and OKT4+ cells correlated with the severity of malnutrition. OKT8+, OKT4+ and OKT4+/OKT8+ ratio of moderate and severe malnutrition with infection were much lower than those without infection. Our findings suggested that main effective and regulative cells of cell-mediated immunity were impaired. OKT3+ and OKT4+ cells might be used as a sensitive index for early assessment of the immune function in malnutrition children. PMID- 1748425 TI - The nation's medical curriculum in transition: progression or retrogression? Reactions to the Robert Wood Johnson Foundation Commission on Medical Education. PMID- 1748426 TI - Iron pigment deposits, small vessel vasculitis, and erythrophagocytosis in the muscle of human immunodeficiency virus-infected patients. AB - Hemosiderin deposition and vascular inflammation were evaluated in muscle specimens from 50 human immunodeficiency virus (HIV)-infected individuals with neuromuscular symptoms. Iron deposits were detected in 25 of 50 cases, and were found more frequently in the distal muscles of lower limbs than in proximal muscles (22 of 30 cases v three of 20 cases; P less than .001). The incidence was higher than in controls (P less than .01). Polyarteritis nodosa was observed in three cases and microvascular inflammation was observed in 27. Direct immunofluorescence showed deposits of both immunoglobulins (mainly immunoglobulin M) and complement in small vessel walls of 19 of 34 patients. The p17 and p24 HIV antigens were detected in three of 27 cases. Both T8 lymphocytes and macrophages were significantly more numerous in patients with Perls'-positive material; these patients also showed vascular inflammation more frequently. Other findings included noninflammatory microangiopathy (18 cases), tubuloreticular inclusions in endothelial cells (one case), and free and intracytoplasmic eosinophilic globules likely representing digested erythrocytes (seven cases). The present study shows that iron pigment deposition in skeletal muscle is a nonspecific finding, frequently observed in the lower extremities of HIV-infected individuals, where it reflects immunopathologic alterations of the microcirculation. Erythrophagocytosis, which may be observed in the muscle of some HIV-infected individuals, may also be implicated. PMID- 1748427 TI - The macrofollicular variant of papillary thyroid carcinoma: a study of 17 cases. AB - We report 17 cases of a distinctive variant of encapsulated papillary carcinoma that is likely to be confused with macrofollicular adenoma or nodular goiter. The tumors showed the unusual combination of macrofollicles and foci of the conventional follicular variant of papillary carcinoma. Macrofollicles occupied over 50% of the cross-sectional areas of the tumors. The macrofollicles were lined either by cells with large ground-glass nuclei, cells with large but less pale nuclei with stippled chromatin, or cuboidal cells with hyperchromatic nuclei. Solid foci were present in four tumors, and a focal insular growth pattern was noted in a fifth tumor. All patients were females ranging in age from 15 to 69 years (mean, 35.4 years). Despite the large size of the tumors (mean diameter, 4.8 cm), only two metastasized to cervical lymph nodes. One of these neoplasms showed extrathyroidal extension, while the other widely invaded the thyroid tissue through the tumor capsule. Multicentric foci of papillary carcinoma with a follicular nonsclerosing growth pattern were demonstrated in the contralateral lobe in two thyroid glands. All patients with follow-up were alive and symptom-free 2 months to 6 years following surgery. PMID- 1748428 TI - Cryptosporidiosis in the acquired immunodeficiency syndrome: a study of 15 autopsy cases. AB - The pathologic changes associated with human cryptosporidiosis have not been well characterized. In this report, 15 cases of cryptosporidiosis in acquired immunodeficiency syndrome patients are described. Organisms were found in autopsy tissue specimens in 13 cases, and only in antemortem stool samples in two. Gastrointestinal/hepatobiliary distribution of organisms was as follows: small intestine (13 cases), extrahepatic bile ducts (eight), intrahepatic bile ducts (seven), large intestine (six), pancreas (five), stomach (three), and esophagus (one). At all sites, infection was usually associated with nonspecific reactive epithelial changes, architectural abnormalities such as villous flattening in the small intestine, and interstitial edema with mixed inflammatory cell infiltrates. Presence of organisms and associated mucosal injury were patchy and of variable severity in the intestine. In the biliary tract, injury was commonly diffuse and severe. Pancreatic duct injury was generally mild and often limited to hyperplastic squamous metaplasia. In late-stage acquired immunodeficiency syndrome patients with cryptosporidiosis, widespread infection in the gastrointestinal and biliary systems by this coccidian was more common and severe than previously suggested. Although the mechanisms have yet to be determined, infection usually is accompanied by pathologic changes that may be causally related to pathophysiologic abnormalities, such as diarrhea and malabsorption, and may account for other clinical manifestations of pancreatitis, cholangitis, and obstructive cholestasis. PMID- 1748429 TI - Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. AB - We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain. PMID- 1748430 TI - Unusual aspects of allergic bronchopulmonary fungal disease: report of two cases due to Curvularia organisms associated with allergic fungal sinusitis. AB - We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions. PMID- 1748431 TI - Immunohistochemistry and gene rearrangement studies in the diagnosis of malignant lymphomas: a comparison of 152 cases. AB - One hundred fifty-two cases (155 specimens) of lymphoproliferative disorders were studied by immunohistochemistry and gene rearrangement analysis. Ninety-five of 96 B-cell lymphomas (99%) showed genotypic B-cell monoclonality. Of these, five cases had rearranged T-cell receptor (TCR) beta chain gene in addition to immunoglobulin heavy chain (IgH) and kappa light chain (Ig-K), one case had rearranged IgH and TCR-gamma chain but not Ig-K or TCR-beta, and two cases had only Ig-K rearrangement. One exceptional case in the B-cell lymphoma group had unrearranged, germline genotypes. In contrast, only 10 of 19 (53%) phenotypic T cell lymphomas had rearranged TCR-beta, eight with concurrent TCR-gamma rearrangement. Of the remaining nine cases, six had germline configuration, two had rearranged Ig-K only, and one had both IgH and Ig-K rearrangement. This last case was reclassified as T-cell predominant, B-cell lymphoma. Thirteen of 16 cases of Hodgkin's disease had germline configuration; three cases had rearranged IgH and Ig-K, of which two were lymphocyte predominant with light chain monoclonality and one was a recurrence. Among 21 reactive lesions, 17 had germline configuration and four had rearranged IgH and Ig-K genes. Of these four cases, two were orbital lesions, one was a partially involved lymph node, and one developed a nodular lymphoma 9 months later. Our results indicate that almost all B-cell lymphomas have IgH and/or Ig-K rearrangement. In contrast, peripheral T cell lymphomas have greater genotypic heterogeneity, and germline patterns for TCR genes are not uncommon. Reactive lesions and Hodgkin's disease tend to retain germline configuration, and any exception is often associated with an unusual clinical setting and/or histology. Genotypic analysis is thus most indicated in B cell lymphomas with equivocal immunohistochemistry findings, T-cell lymphomas, and atypical cases of Hodgkin's disease and reactive lesions. PMID- 1748432 TI - Splenic hamartoma and capillary hemangioma are distinct entities: immunohistochemical analysis of CD8 expression by endothelial cells. AB - The histologic and immunohistologic features of two morphologically similar splenic tumors, a capillary hemangioma and a splenic hamartoma, are reported. The hemangioma was composed predominantly of small vascular channels lined by endothelium expressing factor VIII-related antigen and lacking T-subset antigen (CD8). In contrast, the splenic hamartoma was predominantly a spindle cell lesion with numerous vascular channels coursing through the tumor; these contained splenic-type endothelium expressing both CD8 and factor VIII-related antigen. Our results justify the concept that the splenic hamartoma is a tumor of splenic origin or a true hamartoma and is distinct from the splenic capillary hemangioma. PMID- 1748433 TI - Myxoid leiomyosarcoma of the ovary: analysis of three cases. AB - The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed mullerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis. PMID- 1748434 TI - Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency virus and zidovudine-associated myopathies. AB - Electron microscopic features of muscle biopsies from 13 human immunodeficiency (HIV)-positive patients who had myopathy while receiving zidovudine (AZT) were compared with biopsies from five patients with HIV-induced myopathy who were not treated with AZT. All specimens showed disorganization of the myofibrillar structures, along with a varying degree of nemaline (rod) bodies, vacuolization, inflammation, and endothelial tubuloreticular profiles. One untreated and all AZT treated patients had cytoplasmic bodies, which in the latter were abundant, large, and irregular. Two untreated patients had a peculiar osmiophilic destruction of the muscle fibers, with numerous tubuloreticular profiles in the endothelial cells and brisk inflammation that included lymphoplasmatoid cells. The AZT-treated group had ubiquitous abnormal mitochondria that complemented the presence of ragged red fibers seen by light microscopy. There was subsarcolemmal proliferation of mitochondria, with marked variation in size and shape and proliferation or disorganization of their cristae. Paracrystalline inclusions were seen in one patient. Blind re-examination of the electron micrographs showed abnormal mitochondria that readily distinguished patients with AZT-associated myopathy from those with untreated HIV-induced myopathy. Immunocytochemistry using antibodies to single- and double-stranded DNA revealed severe reduction of mitochondrial DNA compared with the normal nuclear DNA. Although the myopathies associated with HIV and AZT share common myopathologic features, the mitochondrial abnormalities are unique to the AZT-treated patients. Since mitochondrial DNA is specifically reduced, the structural changes noted on electron microscopy are probably associated with mitochondrial dysfunction. Zidovudine, a DNA chain terminator that inhibits the mitochondrial gamma-DNA polymerase, is toxic to muscle mitochondria. PMID- 1748435 TI - Malignant lymphoma of donor origin after renal transplantation: a case report. AB - A case of non-Hodgkin's lymphoma of polymorphous centroblastic type presenting in a renal allograft is reported. The kidney graft was explanted 10 months after transplantation because of chronic rejection. No other manifestations of lymphoma were found in the recipient. Since the human leukocyte antigen patterns of the renal allograft and the recipient differed at two loci, the donor origin of the malignancy could be clearly demonstrated by immunohistochemistry. PMID- 1748436 TI - Malacoplakia of liver: a case report. AB - This is the first reported case in the English literature of malacoplakia of the liver. In common with other cases of malacoplakia, the patient was immunosuppressed secondary to steroid therapy for underlying systemic lupus erythematosus. The patient died 18 months after presentation; at autopsy, the histologic features included those of the late or fibrous stage of malacoplakia. PMID- 1748437 TI - Fatal pulmonary arterial occlusive vascular disease following chemotherapy in a 9 month-old infant. AB - Fatal pulmonary hypertension developed in an infant during the 7-month period in which he received, via a central venous catheter, combination chemotherapy for stage IV neuroblastoma as well as intermittent parenteral feeding. In a lung biopsy and at autopsy, small pulmonary arteries showed diffuse medial hypertrophy and peripheral muscularization, very extensive concentric intimal fibrosis, and focal eccentric fibrosis evolving from organizing thrombi. Pulmonary veins were normal. Hypothetically, chemotherapeutic drug therapy (possibly potentiated either by the parenteral nutrition or simply by the vehicular fluids causing volume loading of the pulmonary circulation) could cause occlusive pulmonary arterial disease by several mechanisms, but the association has not been described previously, although use of such drugs has been reported with pulmonary veno-occlusive disease. PMID- 1748438 TI - An unusual case of hairy cell leukemia: death due to leukostasis and intracerebral hemorrhage. AB - Hairy cell leukemia (HCL) was diagnosed in a 71-year-old Chinese man. His clinical presentation and the characteristics of the hairy cells were typical of classic HCL. However, extreme leukocytosis (195 to 323 x 10(9) cells/L) in peripheral blood was in striking contrast. This leukocytosis, which was much more pronounced than any of the reported cases of HCL with leukocytosis, was associated with leukostasis in the cerebral vasculature and was causally related to a massive intracerebral hemorrhage and death. This mode of death in HCL has not been reported previously. PMID- 1748439 TI - Dynamic polarization vector of spatially tuned neurons. AB - The study of the dynamic properties of otolith neurons has been difficult previously because of the differing response sensitivities of individual cells to specific stimulus directions and the lack of a general mathematical scheme that could explain and account for all their response features. The present paper describes a method for estimating both the spatial and temporal properties of neurons like the otolith neurons that are spatially tuned to different stimulus directions. At each stimulus frequency, a response elipse can be constructed from the neural responses elicited by stimulation along three linear independent axes. The semimajor axis of the ellipse will specify the neuron's direction of maximum sensitivity (polarization vector), whereas the semiminor axis will provide its sensitivity in the perpendicular direction. The predictions of the method for nonzero length of the semiminor axis are qualitatively the same as the experimentally observed dependance of response phase on stimulus orientation. PMID- 1748440 TI - Nonparametric identification of discriminative information in body surface maps. AB - A nonparametric method, based on the Kolmogorov-Smirnov (K-S) test was used to detect significant differences between classes of body surface maps (BSPM's). By systematic application of the method throughout the cardiac cycle, discriminative spatio-temporal information can be identified. In a second method, a Sebestyen linear transformation (SLT) was derived to give estimates of pairwise, linear separability of clinical classes. The utility of the method was illustrated by the pairwise comparison of 40 normal subjects (NOR), 40 patients with anterior myocardial infarction (AMI), and 40 with inferior myocardial infarction (IMI). The application examples demonstrated that: a) diagnostic information in low potential amplitude regions may surpass that in high amplitude regions, b) probability distributions of characteristic features showed small overlap in NOR versus AMI and NOR versus IMI dichotomies although they were not linearly separable, and c) the single best separating potential sample in the K-S sense for NOR versus AMI or NOR versus IMI dichotomies recovered 88 and 73% of the SLT performance, respectively. PMID- 1748441 TI - An assessment of variable thickness and fiber orientation of the skeletal muscle layer on electrocardiographic calculations. AB - This paper assesses the effectiveness of including variable thickness and fiber orientation characteristics of the skeletal muscle layer in calculations relating epicardial and torso potentials. A realistic model of a canine torso which includes extensive detail about skeletal muscle layer thickness and fiber orientation is compared with two other uniformly anisotropic models: one of constant thickness and the other of variable thickness. First, transfer coefficients are calculated from the model data. Then torso potentials for each model are calculated from the transfer coefficients and measured epicardial potentials. The comparison of calculated and observed torso potentials indicates that a simple model consisting of a uniformly anisotropic skeletal muscle layer of 1.0-1.5 cm constant thickness significantly improves the model. However, if photographic slices of the canine torso are used to introduce more detailed data about the variation in skeletal muscle thickness and fiber orientation into the model, the agreement and between calculated and measured torso potentials decreased, although a finite element mesh of over 5000 nodes was used to describe the skeletal muscle in the more detailed model. One source of error increase was considered to be due to numerical discretization and could be reduced with a much finer mesh or by utilizing higher order polynomials to represent the potential distribution within each finite element. However, the results presented in this paper show that high precision computation (64-bit word length) on the mainframe IBM 3081 with an attached FPS-164 gives a slow rate of improvement with reduced discretization intervals and that utilizing higher order polynomials within each finite element gives an even slower rate of improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748442 TI - Errors in frequency parameters of EMG power spectra. AB - Frequency shifts in random signals, e.g., EMG or Doppler ultrasound, can be followed by monitoring one or more parameters of the power spectrum. When such a frequency parameter is determined over a finite length of the signal, a random error and sometimes a systematic error or bias are introduced. Approximate expressions, in terms of moments of the power spectrum, have been derived for bias and standard deviation of the estimates for mean frequency, zero-crossing frequency, and fractile frequency (of which the median frequency is a special case). Experimental results from surface EMG recordings of three human muscles in constant force isometric contractions were in agreement with the theoretical predictions. In this case the mean frequency had the smallest random error. It turned out that the measured values of the zero-crossing frequency can deviate considerably from the predictions by the Rice formula when the amplitude distribution is not exactly Gaussian. In the presence of noise, all frequency parameters show a systematic deviation, depending on the signal-to-noise ratio. In addition to known results on this deviation for mean and zero-crossing frequency, an exact and an approximate expression for the fractile frequency are given. In the case of EMG plus wide-band white noise, the median frequency has the best immunity to noise. PMID- 1748443 TI - Computer analysis of the electrocardiogram during esophageal pacing cardiac stress. AB - It has been estimated that 15 to 30% of patients with suspected or known coronary artery disease are unable to perform an adequate exercise stress test due to a variety of reasons such as obesity, poor physical condition, claudication, etc. Transesophageal atrial pacing has been proposed as a noninvasive alternative for inducing cardiac stress in patients who cannot exercise. Although computer analysis is commonly employed to analyze the electrocardiogram (ECG) during the conventional exercise stress test, the surface ECG recorded during transesophageal atrial pacing is contaminated with large pacing artifacts which confound beat identification by standard computer software. We report the development of a robust signal processing algorithm for interpretation of the surface ECG during transesophageal atrial pacing stress. The algorithm employs novel schemes using both linear and nonlinear transformations to detect and differentiate between the pacing artifact and QRS complex even in difficult situations where the pacing artifact is in proximity to or superimposed on the QRS complex. The algorithm uses sophisticated logic for automatic recognition of sustained capture. It subsequently calculates beat-by-beat and average (over five beats) ST segment amplitude and slope. The algorithm also reports the instantaneous heart rate, RR interval, pace-to-R interval, R-wave amplitude, and estimated sinus node recovery time upon loss of sustained capture. The limitations of present exercise ECG computer methods in processing the ECG during transesophageal atrial pacing stress are evaluated and significantly improved performance by our algorithm is demonstrated. PMID- 1748444 TI - Noninvasive estimation of cardiac output. AB - A noninvasive method of measuring cardiac output is described. The method uses adaptive aorta models in conjunction with femoral and carotid pulse contour waveform measurements to calculate aortic flow. Results are presented from measurements on dogs using internal pressure recordings made with fluid-filled catheters and compared with electromagnetic flow measurements taken in the ascending aorta. Preliminary results using external pulse measurements on patients are also presented and compared with thermal dilution measurements. PMID- 1748445 TI - Detection and imaging of electric conductivity and permittivity at low frequency. AB - This paper is concerned with low frequency electrical impedance imaging, which is the process of constructing images of the electrical impedance of a body's interior based upon measurements of voltage and current made at the body's surface. The electrical impedance accounts for both resistivity and permittivity. This paper shows how permittivity can be exploited to improve the performance of an electrical impedance imaging system. We show that explicit use of the independent information in the data due to the permittivity will ehance a system's ability to distinguish objects in the interior of a body. In addition, we report the results of experiments performed using the Rensselaer ACT 2 system on a saline bath containing various objects. These objects include both living tissue and metal conductors with oxide layers. We demonstrate the system's ability to distinguish these objects, and we exhibit gray scale images of both their resistivity and permittivity distributions. PMID- 1748446 TI - An airjet actuator system for identification of the human arm joint mechanical properties. AB - A system is described for determining the mechanical properties of the human arm during unconstrained posture and movement. An airjet perturbation device is attached to the wrist with a special cuff, and provides high-frequency stochastic perturbations in potentially three orthogonal directions. The airjet operates as a fluidic flip-flop utilizing the Coanda effect, and generates binary force sequences with a steady-state thrust of 4 N, a flat frequency response to 75 Hz, usable thrust to 150 Hz, and a rise time of 1 ms, when the static pressure at the nozzle inlet is 5.5 x 10(5) Pa (80 psi). These operating characteristics are adequate to identify the arm's mechanical properties efficiently and robustly. PMID- 1748447 TI - Automated 3-D reconstruction of vascular structures from high definition casts. AB - Three-dimensional reconstruction and computer modeling is becoming recognized as a powerful tool for studying vascular structures. The computational approach, as well as the computer hardware selected for the task, however, depend upon the information desired. For the modeling of surface geometry, as in the case of the aortic valve, a surface formation technique is favorable over the more computationally demanding volume rendering approach. Automated surface formation, however, requires good quality, high contrast images. We therefore present a technique for producing high contrast images from high definition casts. We also describe the methodology used for automatic contour tracing, generating a mesh of variable density, and the schemes used to reconstruct bifurcating objects. With this approach, 98 mbytes of imaging data could be reduced to 180 kbytes of polygon vertices, and manipulated at near real-time speed on a medium performance graphics workstation. Such a system is therefore well suited for detailed, quantitative analyses of the reconstructed structures. Overall, this paper outlines the procedures used to create a high definition, three-dimensional computer model of any vascular structure. PMID- 1748448 TI - System identification of electrically coupled smooth muscle cells: the passive electrical properties. AB - A system model approach based on a network model is used to investigate the passive electrical properties of coupled smooth muscle cells. This approach makes use of a gradient method of optimization to estimate the passive electrical parameters directly from the magnitude of the input impedance or voltage transfer function of the network model. The need for subjective measurements of parameters and many intermediate steps involved in the analysis using the conventional signal model approach are eliminated. The coupling resistance and capacitance are estimated with sound theoretical and mathematical grounds directly from experimental data. From the simulated results using SPICE, it is evident that the system model approach is accurate, flexible, and reproducible. These properties grant the new approach excellent potential for future studies of drug actions on smooth muscle cells and their associated electrical coupling. Also, sensitivities of the network model with respect to its parameters can readily be obtained. This may provide new insight into the coupling mechanisms of smooth muscle cells. PMID- 1748449 TI - Control of the cryosurgical process in nonideal materials. AB - A study of a controlled cryosurgical process is presented. This study is based on the energy equations describing the probe response and the phase change occurring in the medium. First-order nonlinear differential equations (state equations) are obtained by applying the integral-solution method. In order to obtain maximal cell destruction, it is desired to control a specific cooling rate at the solid liquid interface. This cooling rate defines the desired trajectories of the state variables through the state equations. In order to satisfy the cooling rate condition on the freezing front, a closed-loop is designed to control the probe temperature program. A simple analysis of the system stability employed linearization at several points along the desired trajectories. Ranges of stability were obtained for a system containing a proportional-integral controller. It was demonstrated that these stability ranges depend mainly on the selected sampling time of the discrete control loop and that the phase-change process does not significantly affect the stability results. A complete study of the nonlinear equations was performed by a computer simulation program which enables the selection of the final values of the controller parameters, in order to minimize the error and to ensure stability. In addition, the simulation program gives information about the effects of the A/D and D/A converters accuracy on the performance of the control loop. An A/D converter accuracy of 12 bits was found necessary in order to reduce the oscillations in probe temperature to acceptable values. The simulation also yields a complete calculated temperature field in the tissue during the controlled process. From these simulated results it can be seen that oscillations of +/- 0.5 degrees C in the desired probe temperature do not significantly affect the desired cooling rate at the freezing front. An initial overshoot of 1.5 degrees C in the desired probe temperature was obtained both experimentally and theoretically from the simulation. When this initial overshoot occurs at the beginning of the freezing process, it causes an error in freezing front velocity and consequently in ice front position. From the numerical simulation, it can be deduced that the cooling rate obtained at the front deviates from the desired value by approximately 1%. The probe-temperature error increases at two instants: a) during the super cooling effect and the subsequent sudden crystallization, and b) when the probe temperature is below -80 degrees C and unstable boiling of the cooling medium causes oscillations. PMID- 1748450 TI - The isolation mode rejection ratio in bioelectric amplifiers. AB - Galvanic isolation of a patient during a bioelectric recording is necessary to ensure the safety of the patient. In a typical measurement situation high interference voltages may be present across the isolation barrier. In this paper the necessity of a very high isolation mode rejection ratio--the ability of the amplifier to suppress feed-through from voltages across the isolation barrier to the output--is argued and a design of a multichannel amplifier with an isolation mode rejection ratio of 160 dB is described. PMID- 1748451 TI - Voltage polarity relay--optimal control of electrochemical urea oxidation. AB - Voltage polarity relay (VPR) is shown to optimize the urea oxidation rate and urea current utilization under constant current conditions in direct electrochemical urea oxidation. Direct electrochemical urea oxidation is characterized by reversible deactivation of the working electrode due to oxidation products remaining on the surface and the requirement that the working electrode potential remain below about 1.1 V relative to Ag/AgCl in order to prevent undesirable secondary electrochemical oxidations. The VPR method monitors the potential of the working electrode relative to a suitable reference and changes system polarity when the upper potential set limit is reached. Thus, what was the working electrode becomes the counter electrode and vice versa. Since urea oxidation products are desorbed from the counter electrode when its potential drops below about -0.6 V relative to Ag/AgCl, alternating electrode functions between working and counter provides cyclic electrode regeneration and continuous urea oxidation. VPR is believed to optimize constant current control for any electrochemical system that exhibits behavior similar to direct electrochemical urea oxidation. PMID- 1748452 TI - Nursing for nursing's sake. PMID- 1748453 TI - Kitt Mayo. Interview by Marcy White. PMID- 1748454 TI - I dare you. PMID- 1748455 TI - Patients' rights and DNR decisions. PMID- 1748456 TI - Current bills pending. PMID- 1748457 TI - What's holding back the nurse practitioner movement. PMID- 1748458 TI - Impaired nursing practice: evolution of a professional issue. PMID- 1748459 TI - I found a tumour in my fellow student. PMID- 1748460 TI - Conquering the challenge of student chemical dependence. PMID- 1748461 TI - Collegial support for the addicted nurse. PMID- 1748462 TI - Tennessee Nurses' Peer Assistance Program. PMID- 1748464 TI - "Why I chose nursing as a career". PMID- 1748463 TI - Ethical issues related to chemical dependency. PMID- 1748465 TI - "Why I chose nursing as a career". PMID- 1748466 TI - The new nurse on the block. PMID- 1748467 TI - How to stay sane as a student of nursing. AB - Student nurses experience both developmental and situational stress. While many of these stressors cannot be removed the level of stress experienced is dependent on perception and coping. Feelings of anxiety and stress can be decreased by a student's choice to become actively involved in stress-reduction techniques. This frees the student to experience the excitement and challenge of learning and the joy of helping people. PMID- 1748468 TI - Conservation of a polyanion binding site in mammalian and avian CD4. AB - A polyanion binding site was identified recently on human CD4 which is distinct from the human immunodeficiency virus (HIV)-gp120 binding region but which incorporates the first two immunoglobulin (Ig)-like domains of the molecule. To determine if this site is conserved in other species, several polyanions that blocked monoclonal antibody (mAb) binding to human CD4 were examined for their ability to inhibit the binding of mAb to mouse, rat, pig, sheep and chicken CD4. It was found that aurintricarboxylic acid (ATA) was a particularly effective inhibitor, blocking mAb binding to human, mouse, pig, sheep and rat CD4 by greater than 90% and to chicken CD4 by 80-90%. The polyanions dextran sulphate (DxS), polyvinyl sulphate (PVS) and polyanethole sulphonate (PAS) were also effective inhibitors of anti-CD4 mAb binding in most species, although there were clear species differences in the effects obtained. The polyanions did not inhibit mAb binding to a variety of other cell-surface antigens in the different species, with the exception of sheep CD8, suggesting that the inhibitory effects observed were essentially CD4 specific. Collectively these data indicate that a polyanion binding site is conserved in mammalian and avian CD4. Comparison of the amino acid sequences of human, mouse and rat CD4 revealed that basic residues in human CD4 which could participate in a polyanion binding site are conserved in mouse and rat CD4. It is proposed that this conserved polyanion binding site of CD4 interacts with a sulphated glycosaminoglycan chain which is associated with class II major histocompatibility complex (MHC) molecules containing recently processed antigen. PMID- 1748469 TI - Long-term maintenance of localized antibody responses in the lung. AB - Immune memory cells for antibody production in the lung respond to antigen challenges, providing an important pulmonary defence. However, studies reported here suggested that long-term antibody production in the lung might also be important in pulmonary immune memory. After localized lung immunization and challenges, antibody production of specific IgG and IgA continued in the immunized lung lobes of dogs for months after the last antigen exposure. In addition, the evaluation of lung immunity in dogs immunized and challenged 3 years or 5 years previously (without additional antigen challenge) showed significantly higher levels of specific antibody in lavage fluid from the lung lobe exposed to antigen than in lavage fluids from control lung lobes. Cells from blood or from control lung lobes did not produce significant levels of specific antibody in vitro, whereas cells lavaged from the immunized lung lobes were producing specific antibody. Therefore, long-term antibody production by cells in lung lobes exposed to antigen probably contributed to antibody levels in serum and unexposed lung lobes. Traditionally, lymphoid tissues are believed to be responsible for long-term antibody production. However, antibody production in the lung for years without repeated antigen exposure suggested that other tissues might also be important in long-term antibody production. Maintenance of localized antibody production in the lung would be an important pulmonary defence against infectious agents, but might also play a key role in hypersensitivity lung diseases. PMID- 1748470 TI - Carrier-induced suppression of the antibody response to a 'self' hapten. AB - Immunization of male rats and monkeys with gonadotropin-releasing hormone (GnRH) conjugated to a carrier results in a dramatic atrophy of the prostate. GnRH, linked to either diphtheria toxoid or tetanus toxoid as carrier, is now being evaluated for its use in the immunotherapy of hormone-dependent prostate enlargement in men. This report deals with the phenomenon of carrier-induced, epitope-specific regulation in the GnRH-carrier system. In experiments designed to assess the influence of the carrier on antibody responses to the 'self' hapten GnRH, we show that preimmunization with carriers diphtheria toxoid and tetanus toxoid results in a strain-dependent inhibition of anti-GnRH responses in mice. Results of adoptive transfer experiments indicate that T cells from carrier presensitized mice are responsible for suppression of anti-haptenic antibodies and that T cells from conjugate-immunized mice, on the other hand, can actually help overcome hyporesponsiveness. PMID- 1748471 TI - Influence of cytokines and cellular interactions on the glucocorticoid-induced Ig (E, G, A, M) synthesis of peripheral blood mononuclear cells. AB - We studied the mechanisms of action leading to the glucocorticoid (GC)-induced synthesis of the immunoglobulins (IgE, G, A, M) by human peripheral blood mononuclear cells (PBMC). It is shown that the enhanced Ig synthesis of GC stimulated PBMC is dependent on the presence of T cells and monocytes. After stimulation of purified B cells with GC only a slight enhancement of IgM could be detected. Inhibition studies with neutralizing anti-interleukin-4 (IL-4) and anti IL-6 antibodies revealed that the GC-induced IgE synthesis of PBMC is not dependent on the presence of IL-4 or IL-6. Stimulation of membrane-separated and co-cultured cell fractions revealed that the GC-induced enhancement of IgA and IgM synthesis is mediated by T-cell derived soluble mediators. The GC-induced IgG and IgE synthesis is dependent upon contact of B cells with monocytes. Antibodies against LFA-1 and ICAM-1 are capable to suppress the GC-induced IgE and IgG synthesis of PBMC. Furthermore, the monocyte expression of lymphocyte function antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and HLA-DR is modulated by GC stimulation. PMID- 1748472 TI - Three monoclonal antibodies identifying antigens on all equine T lymphocytes, and two mutually exclusive T-lymphocyte subsets. AB - The aim of this study was to produce monoclonal antibodies (mAb) recognizing equine lymphocyte surface antigens. Fusions were conducted using BALB/c mice hyperimmunized with equine thymocytes. Hybridoma supernatants were screened by flow cytometry and positive hybridomas were cloned twice by limiting dilution. These mAb were then characterized for tissue distribution by immunohistology and flow cytometry, and by precipitation and analysis of the lymphocyte antigens which they recognized. Three mAb (CVS5, CVS4 and CVS8) are described which recognize only T lymphocytes in peripheral blood. Two-colour immunofluorescent studies showed that CVS5 recognized all T lymphocytes and that CVS4 and CVS8 recognized two mutually exclusive subsets of CVS5-positive cells. In the thymus there was a large population of CVS4/CVS8 double-positive cells. Immunohistochemical staining with these mAb was restricted to T-lymphocyte areas. CVS4 and CVS5 precipitated molecules of 58,000 and 69,000 MW, respectively, in both reducing and non-reducing conditions. CVS8 precipitated two molecules of 32,000 and 39,000 MW in reducing conditions, and one molecule of 69,000 MW in non reducing conditions. This evidence suggests that CVS5, CVS4 and CVS8 recognize the equine homologues of CD5, CD4 and CD8, and that the characteristics of these antigens are similar to those of other species. PMID- 1748473 TI - Proliferation of an athymic mouse-derived T-cell clone on thymic stromal cells with interleukin-2. AB - An athymic mouse-derived CD4+8+ T-cell clone, N-9F, was established. It expresses both full length gamma and delta T-cell receptor (TcR) mRNA. N-9F clone was not maintained by interleukin-2 (IL-2) alone but required another soluble mediator(s), contained in concanavalin A-stimulated splenocyte culture supernatant, for its proliferation. By culturing N-9F on thymic stromal cells, [3H]thymidine incorporation was retained and expression of IL-2 receptor (IL-2R) was induced. This phenomenon was also observed on thymic stromal cells from H-2 allogeneic mice, but not on other cell types such as splenic adherent cells or fibroblasts. After addition of recombinant IL-2 into the N-9F culture with thymic stromal cells, N-9F showed enhanced IL-2R expression and greatly proliferated. The inability to detect any soluble factors in thymic stromal cell culture supernatant suggests that this interaction is mediated by direct cell contact between T and thymic stromal cells. Because a CD2-negative subclone, N-9.23, also proliferated on thymic stromal cells, there might exist a type of molecule other than CD2/LFA3 or TcR/MHC involved with thymic stroma and T-lymphocyte interaction. PMID- 1748474 TI - The role of interferon alpha/beta in the induction of intestinal pathology in mice. AB - We have investigated the role of interferon-alpha/beta (IFN-alpha/beta) and IFN dependent effector cells in causing enteropathy in mice. The IFN-inducer polyinosinic:polycytydylic acid (poly I:C) augmented the natural killer (NK) cell activation normally seen in neonatal (CBA x BALB/c)F1 mice with graft-versus-host reaction (GVHR) and exacerbated the systemic and intestinal consequences of GVHR. Poly I:C itself produced a similar pattern of intestinal pathology when administered to normal mice. The effects of poly I:C on NK cell activity and intestinal architecture in normal mice could be reproduced by a single injection of purified IFN-alpha/beta and the intestinal lesions caused by IFN-alpha/beta were prevented by in vivo depletion of NK cells with anti-asialo GM1. These results indicate that IFN-alpha/beta may play an important role in immunologically mediated enteropathies by virtue of its ability to activate NK cells. PMID- 1748475 TI - IL-1, IL-2 and IFN-gamma production by Theiler's virus-induced encephalomyelitic SJL/J mice. AB - Interleukins have been postulated to exert an important modulatory and recruiting role in the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination of the central nervous system (CNS) in SJL/J mice. Using bio- and radioimmunoassays, we have detected and quantified some of the interleukins suspected to play a role in this immune-mediated process. The interleukins 1 and 2 (IL-1, IL-2) and interferon-gamma (IFN-gamma) have been measured in homogenates from the CNS and sera from infected animals, as well as in supernatants from antigen-specific in vitro-stimulated spleen and meningeal cells. IL-1 was detected both in CNS tissue homogenates (approximately 20-40 fmol/ml) and in splenic cultures (200 U/ml). IL-2 was detected only after TMEV-specific antigenic stimulation in spleen cultures (approximately 120 U/ml). In vitro, IL-2 and IL-1 synthesis appear in a dose- and time-dependent manner. IFN-gamma could not be found in any case. The precise nature of IL-1 and IL-2 activity was further assessed by HPLC. The above results strongly indicate the presence of functionally active macrophages in the CNS infiltrates of cells triggering this autoaggressive immune process. In addition, we propose a central role for IL-1 in augmenting the intracerebral immune response leading to the inflammatory demyelination induced by TMEV. PMID- 1748476 TI - Anti-TNF monoclonal antibodies prevent haemorrhage-induced suppression of Kupffer cell antigen presentation and MHC class II antigen expression. AB - Kupffer cells (KC), by virtue of their ability to present antigen (AP) and express major histocompatibility complex (MHC) class II antigen (Ia), play a pivotal role in the host defence system against invading micro-organisms. Although haemorrhagic shock depresses the above KC functions, it is not known whether increased KC tumour necrosis factor (TNF) production and elevated TNF plasma levels following haemorrhage are responsible for it. To study this, C3H/HeN mice were pretreated intraperitoneally with either anti-murine TNF antibody (anti-TNF Ab) or saline. Twenty hours later mice were bled and maintained at a mean blood pressure of 35 mmHg for 60 min followed by adequate fluid resuscitation. Two and 24 hr later, plasma was collected and KC were isolated. AP was measured by co-culturing KC with the D10.G4.1 Th cell clone. Ia expression was determined by direct immunofluorescence. Interleukin (IL)-1, IL-6 and TNF levels in KC supernatants and plasma were measured with bioassays or ELISA. Haemorrhage increased circulating TNF levels by 215% at 2 hr and by 76% at 24 hr (P less than 0.05), which was prevented by pretreatment with anti-TNF Ab. Haemorrhage-induced increase of circulating IL-6 was abolished (P less than 0.05) at 2 hr but not at 24 hr in the anti-TNF Ab group. The suppression of KC AP (P less than 0.05) and Ia expression (P less than 0.05) due to haemorrhage was attenuated (P less than 0.05) in anti-TNF Ab-treated mice at 2 and 24 hr and KC IL-1 and TNF synthesis was further (P less than 0.01) increased. These results indicate that TNF plays a critical role in the initiation and regulation of KC AP, Ia expression, and cytokine production following haemorrhage. PMID- 1748477 TI - Tumour necrosis factor-alpha decreases expression of the intestinal IgG Fc binding site by HT29-N2 cells. AB - Previously, we describe a unique binding site for the Fc region of IgG in human intestinal goblet cells, but regulation of the intestinal IgG Fc binding site (Fc gamma IBS) has not been clarified. In this work, we examined the effects of tumour necrosis-alpha (TNF-alpha) and interferon gamma (IFN-gamma) on expression of the Fc gamma IBS in HT29-N2 colonic cancer cells, which differentiate readily into goblet cells containing the binding site when grown in galactose-containing medium. Expression of the site was monitored immunocytochemically and by ELISA on homogenates of the cells. TNF-alpha in doses of 0.1-100 ng/ml caused a reduction in expression of the Fc gamma IBS and the proportion of cells positive for mucin (as demonstrated by Alcian blue stain), without affecting the viability of the cells. The effects of TNF-alpha on the FC gamma IBS and mucin production could not be attributed to a decreased proliferative rate of the cells, as the cells' incorporation of 5-bromo-2'-deoxyuridine was unaffected. By contrast with TNF alpha, IFN-gamma (i) did not affect the proportion of cells expressing the Fc gamma IBS, (ii) decreased the viability of the cells, and (iii) increased cell proliferation. Additional evidence of specificity of the TNF-alpha effect on the Fc gamma IBS was that TNF-alpha did not affect expression of the polymeric immunoglobulin receptor (secretory component), whereas IFN-gamma increased it. We conclude that TNF-alpha may suppress expression of the Fc gamma IBS by colonocytes and oppose differentiation of the cells towards mucin-producing cells. PMID- 1748478 TI - TNF-alpha reverses the disease-exacerbating effect of subcutaneous immunization against murine cutaneous leishmaniasis. AB - Earlier studies have demonstrated that mice injected subcutaneously or intramuscularly with leishmanial antigens develop significantly exacerbated disease compared with unimmunized controls when challenged with the cutaneous protozoan parasites Leishmania major. We report here that this disease enhancement can be prevented, and protective immunity induced, by the incorporation of recombinant tumour necrosis factor (TNF-alpha) in the immunizing inoculum. This effect of TNF-alpha is dose-dependent and is not evident when TNF alpha and the antigens are injected into separate sites. Furthermore, TNF-alpha injected together with p183, a peptide known to preferentially stimulate Th2 cells and disease exacerbation in H-2d mice, activates spleen and lymph node cells secreting more interferon-gamma (IFN-gamma) and less interleukin-4 (IL-4) and induces a modest but significant degree of resistance against L. major infection in highly susceptible BALB/c mice. PMID- 1748479 TI - The role of the macrophage in induction of immunosuppression in Trypanosoma congolense-infected cattle. AB - Impairment of T-cell function in Boran (Bos indicus) cattle during primary infection with Trypanosoma congolense ILNat 3.1 was found to occur in peripheral blood, spleen and, in particular, the lymph nodes. Lymph node cells from infected cattle failed to proliferate in response to mitogenic stimulus and suppressed proliferation of both normal peripheral blood mononuclear cells and lymph node cells in co-culture assays. The addition of indomethacin, to inhibit prostaglandin synthesis, had no effect on the ability of lymph node cells from infected cattle to suppress the proliferative response of responder cells from uninfected cattle. The supplementation of the culture media with catalase, which degrades hydrogen peroxide, either alone or in combination with indomethacin, also did not result in restoration of proliferation. This suggested the presence of suppressor cells in lymph nodes of infected cattle which exert their effects via a prostaglandin-independent mechanism. By depleting lymph node cells from infected cattle of the monocyte-macrophage population using a cell sorter it was possible to abrogate the previously observed immunosuppression, thus indicating a key role for these macrophages in the induction of trypanosome-associated immunosuppression. PMID- 1748480 TI - Trypanosoma cruzi induces suppression of DNA synthesis and inhibits expression of interleukin-2 receptors by stimulated human B lymphocytes. AB - Trypanosoma cruzi, the causative agent of Chagas' disease, suppresses immune responses during the acute phase and has been shown to induce multiple cellular alterations in activated human T lymphocytes. However, no information is available regarding the effects of this parasite on human B cells. Using an in vitro culture system, in which purified T. cruzi are co-cultured with either peripheral blood mononuclear cells (PBMC) or B-cell-enriched preparations (BCE), we studied whether the organism can induce alterations in DNA synthesis after stimulation with Pansorbin (PS). This response was markedly reduced by the parasite at both suboptimal and optimal PS concentrations, and the extent of the inhibition was augmented as the parasite concentration was increased. Maximal reduction in DNA synthesis was observed when the trypanosomes were incorporated into the cultures at 0 time (i.e. together with PS); the effect was of a much lesser magnitude and undetectable when the parasites were added at 24 and 48 hr, respectively. These results imply that T. cruzi affects a relatively early event during B-cell stimulation. This inference was confirmed by the finding that the proportion of PS-stimulated B cells expressing interleukin-2 (IL-2) receptors was significantly reduced when the parasite was present in the culture. Addition of recombinant human IL-2 did not restore B-cell responsiveness to normal levels. Suppressed B-cell responses were also observed when T. cruzi was separated from the PBMC or the BCE by a cell-impermeable filter, indicating that a soluble factor(s) released by the organism mediated the effect. Accordingly, supernatants of T. cruzi suspensions were found to be suppressive. These results demonstrate for the first time that T. cruzi can affect human B-cell responses and that the mechanism involves inhibition of IL-2 receptor expression. PMID- 1748481 TI - Lack of IgG4 antibody response to carbohydrate antigens in patients with lymphatic filariasis. AB - It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens. To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein [streptolysin-O (SO), deoxyribonuclease B (DB)] and carbohydrate [group A carbohydrate (GAC)] antigens. Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P less than 0.01), and the subclass composition of these antibodies proved heterogenous. Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P less than 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group. These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin. PMID- 1748482 TI - Effect of probenecid on phagocytosis and intracellular killing of Staphylococcus aureus and Escherichia coli by human monocytes and granulocytes. AB - The present study concerns the effects of probenecid on the phagocytosis and intracellular killing of Staphylococcus aureus and Escherichia coli by human monocytes and granulocytes. In both monocytes and granulocytes the inhibitory effect on phagocytosis was very small. Inhibition of intracellular killing of S. aureus by monocytes and granulocytes by probenecid was concentration dependent, being half-maximal at about 2 mM probenecid, and near-maximal at about 5 mM probenecid. The intracellular killing could also be inhibited when probenecid was added when this process was already started. Probenecid also inhibited the intracellular killing of E. coli by granulocytes, but not by monocytes. In the concentration range used, probenecid had no toxic effect on phagocytes or bacteria during the 2 hr of the experiments. PMID- 1748483 TI - Involvement in lupus disease of idiotypes Id.F-423 and Id.IV-228 defined, respectively, upon foetal and adult MRL/Mp-lpr/lpr DNA-binding monoclonal autoantibodies. AB - The derivation of a monoclonal IgG3K autoantibody, designated F-423, from a foetal MRL/Mp-lpr/lpr mouse is described. It has immunochemical properties similar to DNA-binding monoclonal antibodies derived from adult mice with lupus disease in that it reacts with single-stranded DNA and, to a lesser extent, with double-stranded DNA and some forms of RNA. Its similarities to antibodies from adults extend further: it carries a public idiotype, Id.F-423, that can also be detected on antibodies from adult MRL and (NZB x NZW)F1 mice, and F-423 itself expresses other idiotypes defined originally on antibodies from adult lupus mice of both strains. Its potential involvement in pathological processes is demonstrated by two observations: (i) immunization of young MRL/Mp-+/+ mice with antibody F-423 induced the nephritic and immunological changes associated with systemic lupus erythematosus; and (ii) heterologous rabbit anti-Id.F-423 anti idiotypic antibodies suppressed the progression of lupus disease in adult MRL/Mp lpr/lpr mice. Similar effects were found with monoclonal antibody IV-228, an antibody derived from an adult MRL mouse and previously known to be directly nephrotoxic, and with anti-Id.IV-228 antibodies. It is concluded that even during foetal life mice of lupus-prone strains have lymphocytes capable of making pathogenic autoantibodies long before symptoms of lupus disease appear. PMID- 1748484 TI - Prevention of experimental autoimmune uveoretinitis and experimental autoimmune pinealitis in (Lewis x Brown-Norway) F1 rats by HgCl2 injections. AB - Mercuric chloride (HgCl2) induces in Brown-Norway (BN) and (Lewis x Brown-Norway) F1 hybrid rats a transient autoimmune disease characterized by the production of various antibodies to self and non-self antigens and by a dramatic increase of serum IgE. Experimental autoimmune uveoretinitis (EAU) can be induced in Lewis (LEW) and (LEW x BN) F1 hybrid rats by a single immunization with retinal S antigen (S-Ag). Besides uveoretinitis, animals immunized with S-Ag develop an autoimmune pinealitis (EAP). We demonstrate in this study that (LEW x BN) F1 hybrid rats, injected with HgCl2 7 days before S-Ag immunization, are quite efficiently protected against EAU and EAP. We also show that HgCl2-induced protection is neither due to a cytotoxic effect of HgCl2 nor to CD8+ T-cell dependent mechanisms nor to the HgCl2-induced increase of serum IgE concentration. The role of other hypothetical mechanisms, such as anti-S-Ag anti idiotypic antibodies and/or HgCl2-induced unbalance between T-helper cell subsets, is discussed. PMID- 1748485 TI - Effect of advanced ageing on the ability of mice to cause tumour regression in response to immunotherapy. AB - The effect of ageing on tumour immunotherapy was investigated by comparing the ability of aged mice (20 months old) and young mice (3 months old) to cause regression of an established SA1 sarcoma in response to parenteral injection of endotoxin, or to sublethal, whole-body exposure to ionizing radiation. It was found that whereas treatment with either of these agents caused T-cell-dependent regression of the tumour in young mice, it failed to cause regression of the tumour in aged mice. The results are in keeping with extensive literature showing that ageing is associated with a decline in immune competence. PMID- 1748486 TI - Structure function analysis of the H-2 Abp gene. AB - The gene encoding the H-2 Ap class II beta chain was isolated from a B10.P genomic library and sequenced. This gene was also used to construct transfectants of the CH12 lymphoma clone CH12.LX, which express the Abp gene product in association with the endogenous A alpha k chain. We present here the first report of the complete nucleotide coding sequence of Abp. The predicted amino acid sequence of Abp reveals only five residues different from Abq, four of which are present in the mature peptide. These four amino acid changes could account for the differential susceptibility of H-2q vs H-2p mice to the development of collagen-induced arthritis (CIA). Antibodies specific for the transfected Abp protein induce CH12.LX cells to secrete immunoglobulin in the presence of antigen. Comparison of the amino acid sequence with other A beta chains that have been tested in signal transduction experiments suggests that amino acid 9 may be important to the signaling ability of class II A molecules. PMID- 1748487 TI - Structure and expression of mouse germline immunoglobulin gamma 3 heavy chain transcripts induced by the mitogen lipopolysaccharide. AB - Germline immunoglobulin heavy chain gene transcription is though to direct isotype switching by modulating the accessibility of specific switch regions to a recombinase. In this study, cloned cDNA copies of mouse germline Igh-8 RNAs have been used to characterize the Igh-8 transcription unit. The 5' end of these transcripts are derived from an exon denoted Ig3, located 1 kilobase 5' of the Igh-8 switch region. Sequence analysis of cDNA and genomic clones reveals that these RNAs are noncoding. In splenic B cell cultures treated with lipopolysaccharide (LPS), germline Igh-8 transcript levels are upregulated after 8 h due to increased transcription. This induction is consistent with the identification of a putative binding site for the LPS inducible transcription factor NF-kappa B approximately 150 nucleotides upstream of the sites of transcript initiation. Furthermore, nucleotide sequence comparisons reveal that the region encompassing the site of germline Igh-8 transcription initiation is highly homologous to part of the Ig2b exon, and is also conserved upstream of the Igh-1 switch region. The implications of these findings for the control of germline Igh-8 transcription is discussed. PMID- 1748489 TI - Rapid HLA-DPB typing using enzymatically amplified DNA and nonradioactive sequence-specific oligonucleotide probes. PMID- 1748488 TI - Heterogeneity in HLA-DR2-related DR,DQ haplotypes in eight populations of Asia Oceania. AB - The relative distributions of 480 DR2-related DR,DQ haplotypes have been determined in Australian Aborigines, Papua New Guinean Highlanders, coastal Melanesians, Micronesians, Polynesians, Javanese, and Southern and Northern Chinese. Using sequence-specific oligonucleotides (SSOs) for hybridization of polymerase chain reaction (PCR) products from DRB1, DRB5, DQA1, and DQB1 genes, 15 different DR2-related haplotypes were identified. The predominant DR2 haplotype in Oceania involved a novel combination of DRB1*1502, DRB5*0101 alleles; this haplotype occurred sporadically in Java, but not in China. In Southern China, the most frequent DR2 haplotype involved the unusual arrangement DRB1*1602,DRB5*0101; alternatively, DRB1*1602 was associated with a new DRB5 SSO pattern. This study has important implications for molecular HLA-typing protocols that assume particular DRB1, DRB5 or DR,DQ linkage relationships. Further, the novel DRB1, DRB5 haplotype in Oceania suggests that the mixed lymphocyte culture (MLC) determinants Dw2 and Dw12 are discriminated by codon 86 at the DRB1 locus. PMID- 1748490 TI - Pancreatobiliary ductal union in chronic pancreatitis: is the PBDU really guilty? PMID- 1748491 TI - Significance of vasculitis in gut tuberculosis. PMID- 1748492 TI - Role of vasculitis in the natural history of abdominal tuberculosis--evaluation by mesenteric angiography. AB - To investigate the possible role of vascular changes in the pathogenesis of tubercular lesions of the abdomen, findings on barium studies of the bowel and superior mesenteric angiography in 20 patients with abdominal tuberculosis were correlated. Barium studies showed peritoneal lesions in seven patients, isolated intestinal lesions in seven and combined lesions in six. Angiograms were abnormal in all the patients and showed encasement of arteries (13 patients), stretching and crowding of vessels (13), occlusion of vasa recta (5) and hypervascularity (6). All the 13 patients with peritoneal lesions showed arterial stretching, crowding and encasement. Five of six patients with strictures had occlusion of vasa recta. Of seven patients with ulcerations, six had hypervascularity. Our observations suggest that vascular changes occur frequently in abdominal tuberculosis and may explain some pathological and clinical manifestations of this disease. Ulcerated and hypervascular lesions occur in the active and early stages of the disease, and occlusive lesions are associated with healing and 'ischemic' bowel strictures. PMID- 1748493 TI - Upper gastrointestinal mucosal lesions in chronic renal failure. AB - The upper gastrointestinal mucosa was studied endoscopically in 182 patients (140 males, 42 females) with chronic renal failure prior to hemodialysis. Endoscopy revealed normal mucosa in 77 patients (42.3%), inflammatory mucosal lesions in 88 (48.4%), peptic ulcer in 16 (8.8%; duodenal 15, gastric 1) and Barrett's ulcer in one patient. Upper gastrointestinal bleeding was noted at presentation in 16 (8.8%) cases and was associated with erosive gastritis, duodenitis and duodenal ulcer in 11, 3 and 2 patients respectively. Thus patients with chronic renal failure had a high prevalence of inflammatory mucosal changes. PMID- 1748494 TI - Use of esophagostomy in the management of corrosive esophageal strictures. AB - Thirty six cases of corrosive esophageal strictures seen over a period of ten years are presented. The primary treatment modalities followed include antegrade dilatation per oral (11 cases), retrograde followed by antegrade dilatation with endless string per oral (12), retrograde followed by antegrade dilatation with endless string through esophagostomy (12), and surgery (1). Per oral dilatation with endless string was not well tolerated by 15 patients due to friction of the string against the posterior 1/3rd of the tongue, and hence compliance was poor. Dilatation through esophagostomy was easy, and patient compliance was good. Furthermore, patients could be trained to do self bougienage easily through the esophagostomy. Esophagostomy closed within 4-6 weeks after successful distal dilatation was achieved. PMID- 1748495 TI - Misoprostol in the treatment of NSAID-induced gastroduodenal lesions. AB - The cytoprotective effect of misoprostol co-administered with non-steroidal anti inflammatory drugs (NSAIDs) was assessed in a double blind, placebo controlled study. Thirty-seven patients with rheumatoid arthritis receiving NSAIDs, having upper gastrointestinal symptoms and endoscopically confirmed gastric and/or duodenal lesions, were randomised to receive either misoprostol 200 micrograms or placebo tablets twice daily for 4 weeks. Of 31 evaluable cases, 13 of 16 (81%) patients receiving misoprostol showed endoscopic improvement as compared to 10 of 15 (67%) receiving placebo (P:NS). A significant decrease in mean (+/- SEM) mucosal lesion score was observed with misoprostol (from 3.38 +/- 0.32 to 1.32 +/ 0.44; P less than 0.001) but no change was seen with placebo (from 2.80 +/- 0.42 to 1.60 +/- 0.53; P:NS). Symptomatic relief was similar in both groups, being 44% and 40% respectively. Two patients complained of diarrhea in each group and one developed menorrhagia with misoprostol. It is concluded that though misoprostol decreased the number of NSAID-induced mucosal lesions, it was unable to relieve gastrointestinal symptoms. PMID- 1748496 TI - Hepatobiliary and pancreatic ascariasis. PMID- 1748497 TI - Liver transplantation in India: can we afford it now? PMID- 1748498 TI - Liver transplantation in India--are we ready? PMID- 1748499 TI - Thrombotic obstruction of inferior vena cava treated with streptokinase infusion and balloon dilatation. AB - A 35 year old male with thrombotic obstruction of the inferior vena cava superimposed on a membrane was treated by prolonged (48 hours) infusion of streptokinase followed by balloon membranotomy. The procedure produced excellent clinical, hemodynamic and angiographic results which are sustained at the end of six months. PMID- 1748500 TI - Giant cavernous hemangioma of liver. AB - An abscess forming in a giant cavernous hemangioma of the left lobe of the liver is reported. It was treated by lateral segmentectomy. PMID- 1748501 TI - Pancreatic cystadenoma associated with von Recklinghausen's disease. PMID- 1748502 TI - Epiphrenic diverticulum of the esophagus. AB - Esophageal diverticula are rarely found at the terminal portion, where they are called supradiaphragmatic or epiphrenic diverticula and occur in association with motility disorders of the terminal esophagus. We present here two cases of epiphrenic esophageal diverticulum, one of which was treated surgically. PMID- 1748503 TI - Prevalence of HBV markers in hemophiliacs and eunuchs in India. PMID- 1748504 TI - Intestinal malrotation in adults. PMID- 1748505 TI - Scoring system for portal hypertension. PMID- 1748506 TI - Poliomyelitis in India. PMID- 1748507 TI - Adverse events following immunization: 1990. AB - The vaccines used under the Immunization Programme are safe and effective. However, as no vaccine is 100% effective, none is entirely without risk. The benefits of immunization greatly exceed the risks because of the large number of complications and deaths prevented. Although, the risks of vaccine-associated adverse events are extremely low, the occurrence of such events in areas with high immunization coverage levels and low incidence of vaccine preventable diseases can influence public acceptance of immunization services. Moreover, since infections and neurological syndromes are common in the age-groups in which immunizations are given and there are a number of contacts with an infant under the programme, there is a risk of temporally-related severe adverse medical events being attributed to immunization. Monitoring of adverse events is essential to document low risks and to identify programmatic errors, if any, for corrective action. An important, aim of the monitoring system is to disseminate such information to the medical professionals and others associated with the immunization programme. The paper summarizes reports received in 1990, including reports of temporal events where the cause of death was other than immunization. PMID- 1748508 TI - Acute poliomyelitis in children: comparison of epidemiological and clinical features among immunized, partially immunized and unimmunized. AB - This study was conducted to compare the epidemiological and clinical features of acute poliomyelitis among immunized, partially immunized and unimmunized, as these have been postulated to be different amongst these subgroups. Of 614 children with acute poliomyelitis admitted at the Institute of Child Health, Madras, 162 (26.4%) were immunized, 183 (29.8%) were partially immunized and 269 (43.8%) were unimmunized. Poor environmental sanitation, unprotected water source and parental illiteracy were significantly more common among unimmunized group compared to the immunized group. It is concluded that there is no significant difference in symptoms, signs, clinical types, severity of paralysis and case fatality between the immunized, partially immunized and unimmunized. PMID- 1748509 TI - Epidemiology of poliomyelitis in a slum of Bombay. AB - A disease prevalence and immunization coverage survey in a typical slum in Bombay in the year 1988 revealed 93 children with residual poliomyelitis amongst 14,439 children below 9 years of age, indicating high (33.0/100,000 population) annual incidence of poliomyelitis. Only 62 (66.6%) of these 93 lame children sought admission in hospital during the acute phase of illness. The high incidence was attributed to a low immunization (OPV) coverage level in the most vulnerable age group. The immunization coverage for 3 doses of oral polio vaccine below 2 years of age was 43.5%. A large number of children were not commencing their immunization schedule at the right age. The survey indicated a poor "community participation" in the immunization programmes due to a poor "health awareness". PMID- 1748510 TI - Poliomyelitis with special reference to immunization status. AB - One hundred ninety one children below 5 years of age suffering from poliomyelitis were analyzed to find out the immunization status and its correlation with the incidence of poliomyelitis. Effects of age, sex, immunization status and seasonal variation on the morbidity and mortality status were studied. The maximum number of cases were admitted during the months of July (23.6%) and August (23.1%). Of 191 cases, 143 (74.9%) had no immunization and 48 (25.1%) were partially immunized. A total of 155 (81.2%) cases had spinal polio, 23 (12.01%) bulbo spinal polio, and 13 had (6.8%) bulbar polio. Serious illness (bulbospinal and bulbar type) was more in partially immunized children (25%) as compared to unimmunized children (16.8%). The mortality rate was more than two times higher in the partially immunized (29.6%) as compared to unimmunized children (11.2%). The possible explanation for high mortality in partially immunized children could be due to the adverse effect of OPV which has not been studied so far. PMID- 1748511 TI - Vaccine preventable diseases in eastern Maharashtra--a hospital based analysis. AB - A retrospective study of hospital admissions of six vaccine preventable diseases from 1982-86 was carried out to save as a baseline data for future evaluation of vaccination programmes. Children between 1-4 years predominated the admissions in all diseases except whooping cough. The frequency of admissions of tuberculosis showed no change. Measles showed classical cyclical trend. Male female ratio was 1.8: 1.0. The mortality rate in meningeal tuberculosis was not influenced by the immunization status. Relatively small number of admissions of diphtheria and whooping cough indicates a decline due to natural causes or due to intervention programmes. PMID- 1748512 TI - Extent of occurrence of the six vaccine preventable diseases in vaccinated/unvaccinated children. AB - Sixty two children who were diagnosed to be suffering from any of the six vaccine preventable diseases were studied to know their vaccination status prior to the occurrence of these diseases. A total of 33.9% of these children had developed these diseases inspite of full immunization. Nearly 75% of immunized children had received the vaccine from Government sources. The break-up diseases among the children studied was tetanus (35.5%), poliomyelitis and pulmonary tuberculosis (22.6% each), measles (11.3%), diphtheria (6.4%) and pertussis (1.6%). The vaccinated children who developed poliomyelitis belonged to a relatively higher age group. Seventy one per cent of measles cases developed bronchopneumonia as a complication. Seventy five per cent of the mortality in the children studied was due to tetanus neonatorum. Since one third of the children studied had developed diseases inspite of full immunization, it is inferred that closer monitoring of the Cold Chain System and intensive surveillance at peripheral levels are required. PMID- 1748513 TI - Assessment of knowledge and skills about growth monitoring amongst child development project officers. AB - Knowledge and skills about growth monitoring (GM) amongst Child Development Project Officers (CDPOs) were assessed by interview technique. Majority (94%) of subjects had correct knowledge that GM helps in early detection of growth retardation while about 83% felt that a flattened growth curve indicates no weight gain. The percentages of CDPOs who were able to interpret and read correctly about what ascending descending and flattened growth curves indicate were 83, 71 and 50% respectively. There is thus a need of in-service training of CDPOs in GM activities. PMID- 1748514 TI - Lung puncture aspiration in the diagnosis of acute pneumonias. AB - The present study was carried out in 100 children of acute pneumonia to establish the diagnosis of etiologic agents. Clinico-radiological assessment and routine investigations including sputum, throat swab and blood culture did not help in identifying the offending micro-organisms. The bacteriological examination of lung puncture aspirate was the most satisfactory tool for the etiological diagnosis. Direct smear examination/culture were positive in 50% aspirates. On cytology, definite epithelioid granulomas indicated tuberculous infection. However, in direct smear/culture negative patients, predominant mononuclear cell infiltration in the aspirated material may indicate non-pyogenic infection. Staphylococcus aureus (22%) was the commonest organism causing pneumonia in the present study. PMID- 1748515 TI - Antilymphocyte and antithymocyte globulin. PMID- 1748516 TI - Toxic shock syndrome: an unforeseen complication following measles vaccination. PMID- 1748517 TI - Age for assessment of trivalent oral polio vaccination coverage: is there a need for revision in India. PMID- 1748518 TI - Hepatic hemangioendothelioma and neonatal hepatitis. PMID- 1748519 TI - Spondylo-epiphyseal dysplasia tarda with progressive arthropathy. PMID- 1748520 TI - Pattern of pediatric malignancies in Rajasthan. PMID- 1748521 TI - Cerebral cavernous angioma. PMID- 1748522 TI - Primary generalised lymphatic dysplasia. PMID- 1748523 TI - Knowledge of immunization practices in medical students. PMID- 1748524 TI - Cholecystitis with cholelithiasis in a male child. PMID- 1748525 TI - Management of malaria. PMID- 1748526 TI - Artificial organs--an overview. PMID- 1748527 TI - Peptidic uremic retention products. PMID- 1748528 TI - Uremic goiter: the malevolent iodide. PMID- 1748529 TI - Aluminum-citrate interaction in end-stage renal disease. AB - The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption. PMID- 1748530 TI - Fluid-shift during computer-modulated profile hemodialysis (CMP-HD). AB - Computer-modulated profile hemodialysis was examined for patients' comfort and fluid-shift. Fifteen patients were studied after two weeks of dialysis with each of the following profiles: A): constant ultrafiltration (UF) and dialysate sodium (138 mmol/l); B): decreasing UF; C): decreasing UF and decreasing high dialysate sodium (starting 10% above serum-sodium, with a gradual reduction to 138 mmol/l in the fourth hour). Patients with a calculated increase of intracellular volume (ICV) during dialysis had more complaints after dialysis than the others. ICV decreased in all patients with low serum-sodium (less than 136 mmol/l) during all profiles, whereas in patients with higher sodium, only profile C led to a decrease of ICV. However, interdialytic weight gain increased about 75% in patients with low serum-sodium under profile C. The sodium profile could help in preventing imbalance without side effects in patients with high sodium. PMID- 1748531 TI - Plasma exchange (PE) treatment in drug-induced toxic epidermal necrolysis (TEN). AB - Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate. TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings. We describe the clinical course of five patients with severe drug-induced TEN, treated with PE. The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one. Three had a skin involvement affecting almost the entire surface of the body. In addition to the skin lesions, mouth, esophagus and lungs were also involved. Steroids proved ineffective. PE was carried out because of the rapid deterioration of the clinical picture. The mean number of PE sessions was 3.22 (range 1-5). Complete remission of the syndrome was achieved in four patients. One patient died due to septic shock. As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN. PMID- 1748532 TI - A randomized trial of plasmapheresis and subsequent pulse cyclophosphamide in severe lupus: design of the LPSG trial. AB - A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feed-back between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial. PMID- 1748533 TI - Calcification of chemically treated bovine pericardium. AB - One of the most important problems arising in cardiac bioprostheses made with bovine pericardium and, more generally, with biologically-derived tissues is tissue calcification. The present study assessed four chemical treatments on patches of bovine pericardium, intended to avoid or minimize calcification. Pericardium specimens were treated with: A) 0.5% glutaraldehyde; B) 0.5% glutaraldehyde + 4% formaldehyde; C) same as A, but with a further neutralization treatment; D) acylation of fresh bovine pericardium. Circular samples of 1 cm diameter were subcutaneously implanted in the abdominal region of three groups of six rats. The explants were retrieved after 2, 4 and 8 weeks. The calcium content and the histological results showed better behaviour for C and D samples than with the commonly used fixation methods (A and B). The lowest calcification was observed with treatment D, even though its morphological structures were somewhat modified with homogenation of collagen bundles. Among the glutaraldehyde-based treatments, treatment C appears to be the most promising because the pericardium shows slower calcium accumulation with a diffusive pattern. PMID- 1748534 TI - New J-3 flexible-leaflet polyurethane heart valve prosthesis with improved hydrodynamic performance. AB - The aim of this new three-leaflet valve development was to design a leaflet with minimum membrane stresses during performance. This is achieved by manufacturing the valve leaflets shaped almost flat in a medium opening position. Thus, the leaflets have two stable positions, one with maximum opening area and the other with favorable stress distribution in the closed position. The transition between the two end positions is achieved through a two-dimensional rolling motion without buckling and with minimum membrane stresses (bulge forces). The manufacturing technique is dip-coating in polyurethane. Hydrodynamic evaluation of the J-3 valve in steady and pulsatile flow showed minimum pressure drop compared to other commercially available valves. Laser-Doppler-anemometry studies indicated very low shear stresses in the flow field downstream of the valve. In durability tests prototypes have reached lifetimes of up to 17 years. In conclusion, the J-3 valve shows superior hydrodynamic performance thereby reducing potential thrombus formation. Minimization of stresses within the valve leaflets through design could reduce calcification. PMID- 1748535 TI - The simultaneous measurement of glomerular filtration rate (GFR) and renal plasma flow (RPF) following renal transplantation by use of functional imaging. AB - A new method for evaluating renal function using dynamic scintigraphy and deconvolution is described; functional images can be created from the data to quantitate kidney function. Our data are indicating that GFR measurements obtained by this method do not differ from those obtained by classical renal clearance methods. As was expected measurements of renal plasma flow exceed the values of PAH clearance. Additional studies to determine extraction ratios must be done along with direct flow meter measurements. PMID- 1748536 TI - Importance of purification on transfusional efficacy of hemoglobin solutions. AB - It has only been realized quite recently how important is the purification of hemoglobin solution for use in transfusion and several techniques have been published. We used ion exchange chromatography with which the main "contaminants" (glycoproteins, enzymes, phospholipids) are absorbed by the gel, whereas hemoglobin is not retained. The solutions studied here are non-modified hemoglobin and its homologue pyridoxylated hemoglobin (PLP-Hb). Physico-chemical analyses, usually undertaken to characterize hemoglobin solutions, show no difference before and after purification, except that the enzymatic activity almost disappears. In order to appreciate the benefits of purification, total exchange transfusions were carried out on rats. Without reperfusion, purification of the hemoglobin solution allowed a significantly longer survival time which was even more significant with PLP-Hb solution. Urinary loss did not seem to be affected by purification. With reperfusion in order to compensate these renal losses, PLP-Hb solutions gave survival times up to three days. However, the inevitable death of the animals poses the problem of instability of these purified solutions following enzyme loss. PMID- 1748537 TI - Relative pharmacokinetics of three oral 400 mg ibuprofen dosage forms in healthy volunteers. AB - The pharmacokinetic properties of two solid form, 400 mg ibuprofen (IP) preparations, a soft gelatin capsule and a film-coated tablet, were compared to those obtained after the administration of liquid prepared from effervescent IP tablets. IP was absorbed rapidly (tmax 0.6-1.9 h). The fastest absorption was observed after the ingestion of the soft gelatin capsule; liquid and film-coated tablet produced 12.2-7.8 times longer absorption half-lives, 50-39% lower peak concentrations of IP in serum and 3.5-3.2 times higher tmax values. Bioavailabilities were close to similar after all products. All products were tolerated without side effects in this single-dose, crossover study on 14 healthy volunteers. The results of this study support the earlier findings that after oral administration, IP is absorbed equally well from solid formulations as from liquid form. Liquid formulations of IP often deliver slower absorption than expected probably due to incomplete dissolution of the active principle. This may have therapeutic significance, and it should be taken into account when studies on the relative bioavailability of IP from pharmaceutical drug products are planned. PMID- 1748538 TI - Pharmacokinetics of intravenous metronidazole at different dosages in healthy subjects. AB - Metronidazole is effective in the treatment of trichomoniasis and serious anaerobic infections. Individual doses given clinically ranged from 250 mg to 2.0 gm. Most of the available pharmacokinetic data were obtained when the drug was administered at the low end of the dosage range. Several other studies were done using assays that were subject to interference by metabolites. We therefore conducted this investigation to evaluate the pharmacokinetics of metronidazole at different dosage levels in normal subjects in a crossover manner using a specific HPLC assay. Nine male normal volunteers were each administered 250 mg, 1.0 gm and 2.0 gm of intravenous metronidazole in a crossover manner. Serial blood samples were obtained immediately before and at 0, 15, 30, 60, 90 minutes, 2, 4, 6, 10, 24 and 32 hours after the dose. Serum concentrations of metronidazole and its metabolites were determined by HPLC. The half-lives, elimination rate constants, volumes of distribution and areas under the concentration-time curve were calculated. Analysis of variance revealed a statistically significant difference between the low dose (250 mg) and the high dose (1.0 gm and 2.0 gm) effect on the calculated pharmacokinetic parameters. In addition, the production and the elimination of the metronidazole hydroxy metabolite were also found to be reduced when higher doses of the drug were administered. These findings revealed that the pharmacokinetics of metronidazole and its hydroxy metabolite are altered when higher doses of the drug are given; the metabolic transformation of the parent drug is also expected to be reduced. PMID- 1748539 TI - Lack of effect of labetalol on platelet aggregation in hypertensive patients. AB - To evaluate the ex-vivo effects of labetalol, at effective vasodepressor doses, on platelet aggregation in hypertension, 30 hypertensive patients were randomized to either a labetalol or control group in a ratio of two to one. For the labetalol group, the dosage was titrated from 400 mg to 600 mg per day to achieve a fall of 10 mmHg in mean arterial pressure (MAP). No drug was used in the control group. The study lasted for 4 to 8 weeks. At the beginning and end of the study, platelet aggregation to collagen, adenosine diphosphate and epinephrine were measured according to Born's method. In contrast to the significant reduction in MAP, platelet aggregation was not altered by labetalol compared with the control group. Our data do not support the hypothesis that labetalol, at effective vasodepressor doses, inhibits platelet aggregation in mild-to-moderate hypertensive patients. PMID- 1748540 TI - Cmax/AUC is a clearer measure than Cmax for absorption rates in investigations of bioequivalence. AB - In bioequivalence studies, the maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. Cmax is highly correlated with the area under the curve (AUC) contrasting blood concentration with time. Therefore, use of the Cmax/AUC ratio is recommended for assessing the equivalence of absorption rates. The ratio is independent of both intrasubject variations and possible differences in the extent of absorption and reflects only the contrast between the absorption and disposition rate constants (ka/k). PMID- 1748541 TI - Development and present state of hormone replacement therapy. AB - The first therapeutic trials to evaluate the treatment of climacteric symptoms by the administration of ovarian tissue were reported in 1896, i.e. before the endocrine function of the ovary was known or estrogens had been discovered. These were followed by investigations using various ovarian, placental and urine extracts, implantation of ovarian tissue and by oral treatment with dried ovarian tissue. However, reasonably acceptable hormonal drugs did not become available until the third decade of this century, while drugs meeting modern requirements, including that of oral activity, have been available only since the 1940s. It took at least 20 more years before publications for lay people and intensive endocrinological research convinced both the affected women and the medical profession of the value and even the necessity of hormonal treatment for ovarian deficiency sequelae. Nowadays the treatment of climacteric and post-climacteric symptoms with estrogens and progestogens is a highly effective and indeed common practice. However, their use is of less value for the therapy of post-climacteric cardiovascular diseases and osteoporosis. As regards the latter, it may be said that androgenic-anabolic steroids and Org OD 14, a steroid related to norethynodrel, have usefully extended the available therapeutic armamentarium. Estrogens and progestogens are widely used for the prophylaxis of post climacteric osteoporosis and cardiovascular diseases because their exceptional efficacy is well proven. Intensive research has resulted in the development of highly effective and virtually harmless hormonal drugs that are available in a great variety of formulations for all possible modes of administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748542 TI - The influence of food on the absorption of diclofenac as a pure substance. AB - The interaction of diclofenac as a pure substance was investigated without and with concomitant administration of food in 8 healthy, male volunteers (age: 23-29 years, body weight: 60-87 kg). Diclofenac was given as a pure substance by means of a rapid dissolving capsule in a dose of 50 mg. Paracetamol (1.5 g), a marker of gastric emptying rate, was administered simultaneously with diclofenac in order to elucidate the influence of gastric emptying rate on diclofenac absorption. The bioavailability was determined according to the time (tmax) of the concentration maximum in plasma (Cmax) and the area under the curve (AUC). Food significantly delays tmax of diclofenac (without food: [mean +/- SD] 0.8 +/- 0.5 h, range: 0.5 +/- 2 h; with food: 2.4 +/- 0.9 h, range: 1.5-4 h) and diminishes Cmax (without food: 1,125 +/- 765 ng/ml, range: 95-2,100 ng/ml; with food: 434 +/- 151 ng/ml, range: 250-555 ng/ml). The AUC is not influenced (without food: 1,217 +/- 368 ng/ml x h; with food: 1,037 +/- 267 ng/ml x h). The bioavailability of paracetamol is unchanged. It is concluded that the diminishing of Cmax and the delay of tmax of diclofenac are possibly the consequence of an interaction with food and not of the delayed gastric emptying per se. PMID- 1748543 TI - On presentation of the Proctor Award of the Association for Research in Vision and Ophthalmology to Drs. Waldon Wacker and Robert Nussenblatt. PMID- 1748544 TI - Proctor Lecture. Experimental autoimmune uveitis: mechanisms of disease and clinical therapeutic indications. PMID- 1748545 TI - Friedenwald Award and Lecture. Introduction of R. F. Brubaker, Friedenwald Award winner 1991. PMID- 1748546 TI - Flow of aqueous humor in humans [The Friedenwald Lecture]. AB - Based on clinical experiments with fluorophotometry, several observations can be made about aqueous flow through the chambers of the human eye. 1. The rate of flow is 2.75 +/- 0.63 microliters/min in normal subjects, as derived from measurements averaged during normal office hours. The normal range (95%) is 1.8 to 4.3 microliters/min. 2. There is a circadian rhythm of flow, with the highest rates during morning hours, slightly lower rates during afternoon hours, and rates during sleep that are approximately one half of those during the morning. The hormonal basis for this rhythm is unknown, but it is known to be present in both eyes of persons with unilateral Horner's syndrome. 3. A slight decline of the rate occurs after age 10 yr--3.2% per decade. There is no significant difference in aqueous flow between men and women. 4. Of the hundreds of drugs that are used clinically, most are unlikely to have a significant effect on aqueous flow. Exceptions are the beta-adrenergic agonists that, under certain circumstances, are able to increase flow, the corticosteroids that may have a stimulating effect on flow, and three classes of drugs that have therapeutically useful suppressing effects on flow: carbonic-anhydrase inhibitors, beta adrenergic antagonists, and alpha 2-selective adrenergic agonists. 5. Timolol, which has a remarkably consistent suppressing effect on flow during the day, has no effect on the flow of sleeping subjects. By contrast, acetazolamide and apraclonidine are able to reduce the flow of sleeping subjects. 6. Acute doses of beta-adrenergic antagonists and alpha 2-agonists are not additive, but beta adrenergic antagonists and carbonic-anhydrase inhibitors are partly additive. 7. The eye adapts partly to the chronic use of timolol and recovers from its effects when it is discontinued. 8. The rate of disappearance of the effect of beta adrenergic antagonists is longer for the noncardioselective agents, such as timolol and levobunolol, but is relatively short for the cardioselective agent, betaxolol. 9. The rate of aqueous flow is insensitive to moderate changes of intraocular pressure. Clinical studies can provide suggestive leads for more basic investigations or test specific hypotheses. Biochemical, biologic, and pharmacologic approaches in simpler, more controlled experimental conditions are necessary to determine the fundamental processes that bring about aqueous formation in the living eye. The combination of many disciplines (eg, studying molecules, cells, tissues, organs, and the intact living system) has the best chance of furthering our understanding of the aqueous circulation. PMID- 1748547 TI - Transplanted photoreceptors identified in dystrophic mouse retina by a transgenic reporter gene. AB - Dissociated photoreceptor cells from a transgenic strain of mice, containing a bovine promoter lac Z gene construct, were transplanted to the dystrophic retinas of a strain of mice (C3H, rd/rd) without obvious photoreceptors. The transgenic photoreceptor cells expressed beta-galactosidase and were distinguishable from the host retinal cells by light and electron microscopy after the 5-bromo-4 chloro-3-indolyl-beta-D-galactopyranoside histochemical reaction. These results showed that transplanted transgenic photoreceptor cells survived at least 1 month in the host retina and had a primitive outer segment and a well-developed synaptic terminal. PMID- 1748548 TI - Retinal polyol and myo-inositol in galactosemic dogs given an aldose-reductase inhibitor. AB - Galactitol and myo-inositol concentrations were measured in retinas, erythrocytes, and skeletal muscle of experimentally galactosemic dogs receiving a placebo or the aldose reductase inhibitor, sorbinil, for 5 yr. The concentration of galactitol was increased more than 30-fold in the retina and other tissues by galactosemia, and the increase was inhibited 90-96% in all tissues by sorbinil. The concentration of free myo-inositol was greater than normal in retinas of galactosemic dogs, and its concentration was not altered by the aldose-reductase inhibitor. The myo-inositol concentration likewise was greater than normal in the retinas of dogs that were diabetic for 2-4 months. The marked inhibition of polyol production and accumulation in the retina of sorbinil-treated galactosemic dogs was not associated with a comparable inhibition of retinopathy. PMID- 1748549 TI - Cytoskeleton in normal and reactive human retinal pigment epithelial cells. AB - The cytoskeleton of normal and reactive retinal pigment epithelium (RPE) was analyzed immunohistochemically in five light microscopically normal formalin fixed, paraffin-embedded human eyes enucleated because of orbital tumor and in 44 eyes with a uveal melanoma. In 26 eyes, the RPE overlying the tumor was morphologically normal or atrophic; in 18 eyes, hyperplastic changes were present. Normal RPE cells lacked vimentin, but it was present in 35 of 44 eyes with uveal melanoma. Antibodies that recognize cytokeratins CK8 and CK18 labeled normal and reactive RPE cells in all specimens. Although CAM 5.2 and CY-90 detected RPE cells strongly and quantitatively, clones CK5, KS-B17.2, and pancytokeratin antibody lu-5 reacted weakly and did not label some specimens. Immunoblotting supported the presence of CK8 and CK18 in human RPE. Normal RPE cells did not express other simple epithelial cytokeratins, but both atrophic and hyperplastic reactive RPE cells were labeled with antibodies to CK7 or CK19 in 24 of the 44 eyes. Hyperplastic proliferating RPE cells that formed subretinal membranes reacted positively for alpha-smooth muscle actin in 13 of 18 eyes. Antibodies to CK8 and CK18 are valuable markers of normal and reactive human RPE cells, but a panel of reagents is necessary to document reactive changes in the cytoskeleton. Acquisition of alpha-smooth muscle actin by human RPE cells may be related to their ability to form periretinal membranes and contribute to intraocular proliferative diseases. PMID- 1748550 TI - Localization of alkaline phosphatase on basolateral plasma membrane of normal and regenerating retinal pigment epithelium. A cytochemical study in rabbits. AB - Ultrastructural cytochemistry was used to analyze the polarized distribution of alkaline phosphatase (AP) on the plasma membranes of normal and regenerating retinal pigment epithelium (RPE) and the ciliary body epithelium in rabbits. The AP activity was concentrated on the basolateral plasma membrane in normal RPE. In regenerating RPE (after intravenous administration of sodium iodate to damage the RPE), there was a differential expression of AP activity according to the site on the regenerating epithelial sheet. At the edge of the sheet, where cells were undifferentiated and immature (ie, without the polarized distribution of basolateral and apical plasma membrane specializations seen in normal RPE), no plasma membrane AP activity was observed. The AP activity was reexpressed more proximal in the regenerating sheet. It was first evident where contiguous cells formed junctional complexes and cytologic polarization again became apparent. New AP activity was restricted to the basolateral plasma membrane. Eventually, the polarized distribution of AP activity seen in normal RPE was reestablished. In the ciliary body, AP activity was localized to the basolateral plasma membranes of the outer, nonpigmented epithelial cells. It was concluded (1) that cytochemical activity for nonspecific AP is concentrated on the basolateral plasma membrane domain of normal RPE and the normal pattern of AP activity is lost initially and then reexpressed. PMID- 1748551 TI - Studies of tumor-infiltrating lymphocytes from a human choroidal melanoma. AB - Cell suspensions prepared enzymatically from an ocular choroidal melanoma were cultured in vitro in an effort to generate (1) melanoma tumor cell lines and (2) tumor-infiltrating lymphocytes cytotoxic for ocular melanoma cells. Even though histologic study of the tumor did not show "significant" infiltrating bone marrow derived cells, lymphocytes were generated readily in cultures to which interleukin-2 was added. Phenotypic analysis of the cultured lymphocytes indicated that T-cells, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were present. Moreover, functional studies of the cultured lymphocytes revealed NK activity, LAK activity, and most importantly, tumor antigen-specific cytotoxic T-cell activity. It was concluded that it is possible to obtain tumor cell lines and tumor-infiltrating lymphocytes from ocular tumors, both of which would be required if cellular immunotherapy of ocular tumors is contemplated. In addition, these results indicate that ocular melanomas can express unique tumor-specific antigens and that the immune system of a patient with such an ocular tumor can perceive these tumor antigens because antigen specific precursor cytotoxic T-cells were present in the tumor-containing eye at the time of enucleation. The theoretic and therapeutic implications of these findings are discussed. PMID- 1748552 TI - Pharmacokinetic study of recombinant human epidermal growth factor in the anterior eye. AB - This study investigated the pharmacokinetics of recombinant human epidermal growth factor (EGF) in the eyes of live rabbits and enucleated human eyes. After intracameral injection of 1.2 muCi (1.1 micrograms) of 125I-EGF into rabbit eyes, tissues in the anterior segment were analyzed for uptake of 125I-EGF after 1, 2, 4, and 24 hr. The half-life of EGF during the initial 4 hr was 1.3 +/- 0.6 hr (+/ the confidence limit at P = 0.05) in the cornea, 0.7 +/- 0.4 hr in the iris, 1.9 +/- 0.9 hr in the lens, and 0.6 +/- 0.5 hr in the aqueous humor (n = 18 for each tissue). Between 4-24 hr, the percent retention of EGF in the tissues (relative to the initial amount in respective tissue) is in the order of lens greater than cornea greater than iris greater than aqueous humor. The kinetics of EGF uptake by excised human corneas was determined by incubating the endothelial surface with 1.2 muCi/ml (100 ng/ml) of 125I-EGF for 4 hr at 37 degrees C or 4 degrees C. After 4 hr, the total amount of EGF accumulated in the corneas was 2.3 +/- 0.2 ng (+/- standard deviation; n = 6) at 37 degrees C, and 1.4 +/- 0.1 ng at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748553 TI - Tobramycin liposomes. Single subconjunctival therapy of pseudomonal keratitis. AB - The authors compared 24 doses of hourly topical fortified tobramycin (Group A) therapy with a single subconjunctival administration of multivesicular megaliposome-encapsulated tobramycin (Group B) and free subconjunctival tobramycin (Group C) in treating a rabbit model of keratitis caused by Pseudomonas aeruginosa. One cornea each of 50 rabbits was infected with P. aeruginosa for 24 hr. The animals then were divided randomly into five groups of ten each. Groups A, B, and C were treated as described. Group D received liposomes without tobramycin and Group E, hourly balanced salt solution. Significantly fewer Pseudomonas colonies were present in the corneas of all three drug-treated groups (A, B, and C) compared with the two control groups (D and E) at 24 hr (P less than 0.005). Significantly fewer Pseudomonas colonies were present in Groups A and B compared with Group C (P less than 0.02). No significant difference was noted between Groups A and B (P = 0.30). Tobramycin encapsulated in megaliposomes may be useful in treatment of pseudomonal keratitis. PMID- 1748554 TI - In vivo fibroplasia of a porous polymer in the cornea. AB - We have developed a melt-blown fibrous construction of polybutylene/polypropylene in which we previously demonstrated keratocyte ingrowth and collagen synthesis in vitro. In the present studies, we evaluated this material in vivo in interlamellar corneal pockets for periods of up to six months. By day 42, the porous interstices of the disc were heavily populated with keratocytes. Extracellular matrix deposition occurred and there was a 5000-fold increase in total protein and a 1000-fold increase in total collagen over background. The cells within the disc continued to be synthetically active for the six months of our study. Discs remained in corneas for periods of up to one year without any extrusion. This material has great promise as a porous peripheral component of a keratoprosthetic device. PMID- 1748555 TI - Correlation of chromatic, spatial, and temporal sensitivity in optic nerve disease. AB - Spearman rank-order correlations (R) were made between the color-mixture threshold, spatial contrast sensitivity, and flicker sensitivity measurements of 38 patients with a variety of optic nerve disorders. Patients had to satisfy the following criteria: greater than 0.5 log unit loss of chromatic or achromatic sensitivity (compared to age-matched normals), central fixation, no congenital color defects, and no ocular media abnormalities. The results of the analysis show a significant correlation between selective losses of high spatial frequency sensitivity (relative to low) and selective losses of red/green and blue/yellow sensitivities [R = -0.680 (P less than 0.001) and R = -0.439 (P less than 0.01), respectively]. A mild correlation was found between selective spatial and selective temporal losses [r = -0.399 (P less than 0.05)] (ie, low temporal frequency losses correlate with high spatial frequency losses and vice versa). A stronger correlation was found between selective red/green and selective blue/yellow sensitivity losses [R = 0.657 (P less than 0.001)]. No correlation was found between selective temporal losses and selective chromatic losses. These findings can be explained in terms of differential losses of three types of fibers: (1) fibers that are particularly sensitive to red/green color, high spatial and low temporal frequencies; (2) fibers signalling blue/yellow color; and (3) fibers that are relatively sensitive to high temporal frequencies and low spatial frequencies. PMID- 1748556 TI - Optic nerve head blood speed as a function of age in normal human subjects. AB - We used the laser Doppler technique to determine the relation between age and the speed of blood cells moving through the capillaries of the optic nerve head. We studied 22 normal human volunteers ranging in age from 16-76 years. The results were best described by a statistically significant quadratic relationship between capillary blood speed and age. Blood speeds were lowest in the youngest and oldest subjects and highest in subjects between 27 and 35 years old. A two-phase linear model showed a statistically significant 20% decrease in blood speed in volunteers between the ages of 31 and 76. The results were not affected by gender, degree of refractive error, systemic blood pressure, intraocular pressure, cup/disc ratio of the optic nerve head, or by site-to-site differences in the light scattering properties of the optic nerve head tissue. Capillary blood speed was, on average, 15% greater from temporal sites than from nasal sites, corresponding to the equally greater distribution of ganglion cell axons within the same area. The results provide a baseline of normal age-controlled data that can be compared to measurements obtained from patients with disorders of the optic nerve head thought to have a vascular etiology. PMID- 1748557 TI - Identification of lectin binding proteins in human tears. AB - The identity of glycoproteins in stimulated normal human tears was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of tears onto minigels, blotting, and subsequent incubation with different biotinylated lectins (concanavalin A [Con A], peanut agglutinin [PNA], glycine max agglutinin [SBA], Phaseolus vulgaris agglutinin, wheat germ agglutinin [WGA, native form], Artocarpus integrifolia agglutinin [Jacalin], and Pisum sativum agglutinin). Control proteins included purified secretory immunoglobulin A (sIgA) from human colostrum, human milk lactoferrin, and chicken-egg lysozyme. All samples were prepared in a denaturing (SDS) buffer under nonreducing and reducing conditions. The sIgA in tears and IgA (alpha) heavy chain fragments (reduced sample) were identified with most of the lectins tested. A particular high molecular weight (greater than 200 kD) protein fraction in tears that just entered the separation gel on SDS-PAGE was detected with WGA and Jacalin. This fraction stain poorly with silver. Tear lactoferrin was identified with all lectins used, although binding was low with SBA. Purified milk lactoferrin showed a poor reaction with Jacalin, but a protein in tears of similar mobility bound this lectin (nonreduced samples). Under both nonreducing and reducing conditions, tear-specific prealbumin in tears did not bind any of the lectins tested. Tear lysozyme only reacted with lectin after reduction. The techniques described may provide additional valuable information in addition to commonly used methods for tear protein analysis and further knowledge concerning the role of glycoproteins on the ocular surface. PMID- 1748558 TI - Ocular hypothermia depresses the human pupillary light reflex. AB - Twelve human volunteers were studied to determine the effect of eye surface cooling on the parameters of the light reflex. Surface cooling resulted in a 38% decrease in the maximum constriction velocity and a 36% decrease in the maximum redilation velocity. These changes were thought to be the result of a "sluggish" response of the pupillary sphincter. PMID- 1748559 TI - Accommodation and ciliary muscle muscarinic receptors after echothiophate. AB - Twice daily topical administration of echothiophate for 2 weeks to the eyes of living cynomolgus monkeys produced profound subsensitivity of the accommodative response to pilocarpine and an approximately 50% decrease in the number of specific binding sites for 3H-quinuclidinyl benzilate (3H-QNB) in the ciliary muscle without a change in their affinity. When echothiophate treatment was discontinued, functional cholinergic sensitivity and the number of QNB binding sites both returned to normal over a similar 4-8 week period. Most animals had a modest overshoot of both functional sensitivity and number of binding sites for at least several weeks thereafter. The treated to control eye ratios for the number of binding sites and accommodative response to pilocarpine were correlated and the plot of log treated to control binding site ratio versus treated to control accommodation ratio resembled a dose-response curve. Similarly, the treated versus control eye differences for the two parameters were correlated, with the regression line passing through the 0-0 axis intercept. Collectively, these findings suggest that agonist-induced modulation of functional cholinergic sensitivity in the parasympathetically innervated (as opposed to denervated) ciliary muscle occurs by a muscarinic receptor-mediated mechanism. This system appears to provide a useful model to study the regulation of ciliary muscle cholinergic sensitivity. PMID- 1748560 TI - Upper eyelid movements measured with a search coil during blinks and vertical saccades. AB - Upper eyelid movements were recorded in nine human subjects by mounting a miniature coil of wire directly on the eyelid and subjecting the search coil to a vertically directed alternating magnetic field. The metrics of blinks and lid movements accompanying saccades were described by "main sequence" relationships, linking maximum velocity to amplitude and duration to amplitude. In general, lid movements were faster than those reported previously in the literature, but there was considerable intersubject variability. On average, the main sequence relationships for blinks were independent of either starting lid position or whether the blinks were generated spontaneously, reflexively, or voluntarily. For the down phase of the average blink, both the maximum velocity and duration increased almost linearly with amplitude. The maximum velocity of the down phase was faster than that of the up phase. For lid movements accompanying vertical saccades, the maximum velocities in the up and down directions were similar and increased nonlinearly with amplitude, saturating at about 120 mm/sec (approximately 450 degrees/sec). Duration increased approximately linearly with amplitude. The down phases of blinks were much faster than those of saccade related lid movements. By comparison, the maximum velocities of the up phase of blinks and of saccade-related lid movements were almost equal. The large intersubject variability suggests caution when using normative data to interpret abnormal lid motion for clinical purposes. PMID- 1748561 TI - Evaluation of sensitivity and specificity of spatial resolution and Humphrey automated perimetry in pseudotumor cerebri patients and normal subjects. AB - To determine the sensitivity and specificity of high-pass resolution perimetry ("ring test"), 18 patients with pseudotumor cerebri (PTC) and 18 age-matched controls were examined with the Humphrey program 24-2 and the ring test. Goldmann perimetry also was done to determine if defects found with the ring test were present with another method. Testing with Humphrey perimetry revealed defects in 15 PTC patients and four control subjects; with the ring test, 13 PTC patients and two control subjects had abnormalities. The disturbed areas in the control subjects with both automated tests were not reproducible. Humphrey perimetry had a sensitivity of 83% and the ring test, 72%. The specificities were Humphrey perimetry, 78% and the ring test, 89%. These differences were not statistically significant. Qualitative assessment of the presence and extent of damage using the pointwise probability plots and graphically displayed raw data showed good correlation of the tests in 11 of the 18 patients. The lack of correlation in four of the patients was caused by the presence of a generalized depression or a peripheral contraction on the Humphrey test; this defect, not present on retesting, may have been related to fatigue or poor motivation. The ring test is a sensitive and specific perimetric technique in patients with PTC. PMID- 1748562 TI - The relationship between synthesis of secretory products and reducing capacity in pancreas and parotid acinar cells. AB - The secretory products in exocrine pancreas acinar cells in utero were found to reduce osmium tetroxide. This reducing capacity was also exhibited by adult pancreas and parotid glands in different phases of synchronized secretion, and after single or chronic administration of a secretagogue, pilocarpine or isoprenaline. In utero, the reducing capacity appeared in the pancreas concomitantly with the synthesis of secretory products, and was limited to the transitional vesicles on the cis Golgi side. After birth, osmium staining occurred in the cis Golgi vesicles and cisternae of both glands. In the chronically-treated parotid gland, where the occupational programme for secretory proteins had been altered, the reducing capacity was diminished, resembling that in embryonic exocrine pancreas. PMID- 1748563 TI - A quantitative cytochemical investigation of osteoclasts and multinucleate giant cells. AB - Quantitative cytochemical, immunocytochemical, autoradiographic and electron cytochemical investigations have been used to compare osteoclasts with multinucleate giant cells that had been freshly obtained from the same animal. The levels of beta-acid galactosidase activity, the DNA in individual nuclei and the cellular protein content were similar in both cell types. However, osteoclasts generally possessed greater acid phosphatase and NADH dehydrogenase activity but lower levels of fluoride-inhibited non-specific esterase activity than multinucleate giant cells. The acid phosphatase activity in multinucleate giant cells was completely inhibited by 100 mM tartrate, but in osteoclasts only a 20% reduction in activity was observed. Formation of multinucleate giant cells in a "bone microenvironment" (thin bone slices) did not increase their content of tartrate-resistant acid phosphatase activity. Moreover, in osteoclasts, endogenous peroxidase activity was undetectable but present in several granules within the cytoplasm of multinucleate giant cells. Osteoclasts and multinucleate giant cells displayed a similar microtubules distribution, but calcitonin, which induced rearrangement of microtubules and cellular contraction in osteoclasts, had no effect on multinucleate giant cells. Thus, these investigations reveal both similarities and differences between these two syncytia and support the hypothesis that osteoclasts and multinucleate giant cells are related. Possibly osteoclasts arise from monocyte progenitors before commitment to a macrophage lineage has occurred. PMID- 1748564 TI - Localization of the gene transcripts of 11 beta-hydroxylase and aldosterone synthase in the rat adrenal cortex by in situ hybridization. AB - Using in situ hybridization, localization of the gene transcripts of 11 beta hydroxylase and aldosterone synthase was investigated in order to clarify the sites for the synthesis of corticosterone (glucocorticoid) and aldosterone (mineralocorticoid) in the rat adrenal cortex. The gene transcript of 11 beta hydroxylase was localized in all the endocrine cells of the entire adrenal cortex, while that of aldosterone synthase was exclusively confined in zona glomerulosa cells. These results represent that every endocrine cell of all the cortical zones synthesizes 11 beta-hydroxylase which converts 11 deoxycorticosterone to corticosterone, and only glomerulosa cells synthesize aldosterone synthase which produces aldosterone from corticosterone. Thus it is clearly shown that zona glomerulosa cells synthesize mineralocorticoid, while zona fasciculata as well as reticularis cells produce glucocorticoid. PMID- 1748565 TI - Undegraded chromogranin A is present in serum and enters the endocytotic lysosomal pathway in kidney. AB - Analysis of human and bovine serum by immunoblotting revealed the presence of the proprotein chromogranin A. By the same method chromogranin A was also found in rat, bovine and human kidney. However this organ did not contain any chromogranin A mRNA arguing against a synthesis within this organ. By immune-electron microscopy chromogranin A immunoreactivity was found in proximal tubule cells of rat kidney. Positive immunostaining was present in small vesicles within and in close proximity to the brush border and closer to the nucleus in typical lysosomal structures. These results make it likely that chromogranin A from serum reaches kidney tubule cells by glomerular filtration and is taken up into the endocytotic lysosomal pathway. PMID- 1748566 TI - Uptake, distribution and binding of vertebrate and invertebrate steroid hormones and time-dependence of ponasterone A binding in Calliphora vicina. Comparisons among cholesterol, corticosterone, cortisol, dexamethasone, 5 alpha dihydrotestosterone, 1,25-dihydroxyvitamin D3, ecdysone, estradiol-17 beta, ponasterone A, progesterone, and testosterone. AB - The presence of specific binding sites for radiolabelled vertebrate-type and arthropod-type steroid hormones was investigated in several organs including salivary gland, and central nervous system of third instar Calliphora vicina larvae by thaw-mount autoradiography. Ponasterone A, a 20-hydroxyecdysone agonist and 20-hydroxyecdysone are the only steroids which bind to nuclear high affinity binding sites. These binding sites are DNA associated while nucleoli show no tracer binding. Ecdysone, an endogenous 20-hydroxyecdysone precursor, is taken up by target cells but no significant nuclear binding occurs. 1,25-Dihydroxyvitamin D3 concentrates in cytoplasm only and its uptake is highest compared to all other steroids. Progesterone and testosterone show weak accumulation in the cytoplasm, while for cholesterol, corticosterone, cortisol, dexamethasone, dihydrotestosterone and estradiol-17 beta, no noticeable uptake occurs. For ponasterone A, a clear time dependence of uptake and intracellular distribution is visible, suggesting the existence and involvement of specific ecdysteroid uptake and transport mechanisms. These results suggest the presence of binding sites for various mammalian steroids in insects. Whether vertebrate steroid hormones or metabolites of them play a role in insects or whether the uptake and binding is based on chemical similarities alone without biological significance remains to be further investigated. PMID- 1748567 TI - Expression of facilitative glucose transporter in rat liver and choroid plexus. A histochemical study in native cryostat sections. AB - Two isoforms of facilitative glucose transporters (GLUT), namely the erythroid/brain-type GLUT 1 and the liver-type GLUT 2, were demonstrated in native cryostat sections of normal rat liver and brain by immunofluorescence and a very sensitive immunoalkaline phosphatase reaction. Fixation with 0.1% alcoholic periodic acid resulted in an excellent localization of GLUT 2 in liver and GLUT 1 in brain. GLUT 1 in liver, however, could successfully be demonstrated after fixation with 1% alcoholic formaldehyde. GLUT 2 occurred in all hepatocytes as a basolateral membrane protein with a gradient of high expression in the periportal area and a lower one in the perivenous part. The first layer of hepatocytes adjacent to the hepatic vein coexpressed GLUT 1. In addition, GLUT 1 could be detected in the smooth muscle layer of the portal vein and in the apical and lateral plasma membrane of the bile duct epithelium. In brain, GLUT 1 showed a high expression in the microvessels, the ependyma and in the basal plasma membrane of choroid plexus epithelial cells. The blood capillaries associated with the choroidal epithelium were, however, negative for GLUT 1. The importance of the new findings in this study for the physiological role of the respective facilitative glucose transport proteins is discussed. PMID- 1748568 TI - Identification of lymph and blood capillaries by immunohistochemical staining for various basement membrane components. AB - In the present report we analyzed the presence and distribution of various basement membrane (BM) proteins in normal blood and lymph vessels with special emphasis on BM-associated heparan sulfate proteoglycan (HSPG) when compared to the BM-components collagen IV, laminin and fibronectin. We found that normal lymph capillaries have a BM that contains only collagen IV and small amounts of laminin, but almost no BM-associated HSPG and fibronectin, while blood capillaries showed a BM comprising of all components tested for. Larger lymphatics, however, were indistinguishable from blood vessels on the basis of BM staining. Lymphangiomas showed a BM pattern similar to that of lymph capillaries. Our findings provide evidence that the differential staining of BM-components may represent a reliable method for morphological distinction between blood and lymph capillaries. A comparison of these results with the BM-pattern in other functionally specialized blood vessels (glomerulus, sinusoids) provides evidence that the BM-composition may have some major impact on the functional properties. Thus, it is conceivable that the lack of HSPG in lymph capillaries may be essential for a free influx of fluid and proteins into these capillaries, which may have been extravasated into the interstitium. PMID- 1748569 TI - [ENT antibiotic therapy: therapeutic guidelines. Part I]. AB - We discuss the variety of ear, nose and throat infections and then define the criteria for the choice of an adequate antibiotic. The importance of "supercalculated" therapy based on the results of Gram's stain is stressed, as it can save patients from over-treatment and adverse side-effects. Indications for Gram's stain in ENT as well as the value of the characteristics of the pus produced by different pathogens are described. The severity of the infection determines the choice between parenteral or oral therapy. The importance of the decision taken on the 1st and 3rd day of a severe infection is emphasised. Therapeutic principles in ENT infections are shown by grouping different infections with a similar spectrum of pathogens; also the indications for antibiotic therapy are outlined. Finally the priority of antibiotic treatment in some surgical infections is mentioned, and the peri-operative prophylaxis and treatment are described as well as the guidelines for treatment of infectious post-operative complications. PMID- 1748570 TI - [Acute inner ear deafness]. AB - Sudden inner ear hearing loss initially might suggest a psychogenic disorder of hearing, particularly when it is bilateral and simultaneous. The differential diagnosis includes disseminated encephalitis, syphilitic labyrinthitis and Cogan's syndrome. The history and cause of acute bilateral deafness in meningitis are easy to recognise. Furthermore, unilateral acute inner ear deafness should not be regarded as idiopathic without further consideration. A acoustic neuroma is a possible cause even of a low-tone hearing loss. More controversial is rupture of the round window membrane as a cause of sudden deafness. The deafness after epidemic parotitis obviously leads to a total unilateral hearing loss in every case. Even labyrinthine apoplexy with loss of hearing and vestibular function can be caused by a tumour of the cerebellopontine angle. Idiopathic sudden deafness should be defined as an acute sensory hearing loss whose anatomical basis in an acute vascular endolymphatic hydrops of unknown cause. The sudden deafness affects only one ear; tinnitus and brief vertigo can be accompanying symptoms. A sudden hearing disorder due to other causes should be distinguished from idiopathic lesions. PMID- 1748571 TI - [Angioarchitecture of the cricoid cartilage and anterior trachea]. AB - Two dense capillary networks have been described lying in the anterior and posterior parts of the human cricoid cartilage. Between these two lies an area supplied by a very sparse capillary network. The anterior sector is derived from branches of the cricothyroid and inferior laryngeal arteries, the posterior from branches of the superior and inferior laryngeal arteries. The tracheal cartilages are supplied from above downwards by circular branches derived from two parallel longitudinal arteries. Therefore the centre of each cartilage is very sparsely supplied by small arteries. PMID- 1748572 TI - [Endogenous tracheobronchial foreign body. An indication for emergency bronchoscopy with a rigid bronchoscope]. AB - We report two patients, a 3-year-old child and a 75-year-old woman, with a foreign body of the trachea, and of the entire tracheobronchial system respectively. We emphasise the importance of rigid endoscopes for foreign body extraction and for respiration. Also, we describe the differentiation of endogenous from exogenous foreign bodies of the tracheobronchial system. PMID- 1748573 TI - [Semi-automatic TNM classification of malignant tumors with the ESTER system exemplified by the larynx]. AB - Classification of tumours according to the TNM scheme has been accepted worldwide. However, vague baseline assessments and borderline cases render a comparison of the outcome on the basis of TNM classification impossible. Therefore we integrated the TNM rules as a new algorithm into an existing expert system for determining therapy. Thus, every tumour documented with the ESTHER system is automatically classified according to current TNM rules. The program is designed to cope with future changes of the TNM system: raw data are used for classification so that only the algorithms need to be modified. PMID- 1748574 TI - [Subglottic metastasis of multiple myeloma. Case report and review of the literature of laryngeal plasmacytoma]. AB - A total of 111 cases of laryngeal plasmacytoma have now been reported. The disease may present either as a primary extramedullary plasmacytoma (n = 90) or as a metastasis of a multiple myeloma (n = 21). The distinction between these two types is very important in therapy and prognosis. We report a subglottic plasmacytoma in a 48-year-old woman. Investigations showed bone marrow infiltration, osteolysis and light chain expression in serum, indicating generalized disease. Therefore polychemotherapy was given, during which complete macroscopic and microscopic regression of the laryngeal plasmacytoma was observed. However, 14 months later, the patient died of renal failure due to systemic progression of the multiple myeloma. PMID- 1748575 TI - [Life threatening adverse effect of captopril]. PMID- 1748576 TI - [Non-neoplastic central hearing loss--a review]. AB - Acquired central auditory disorders not due to a tumour are unusual. The well known conditions such as hypoxic encephalopathy, erythroblastosis, bacterial meningitis and trauma are reviewed. Recent experimental and clinical studies contribute to progress in the understanding of the pathogenesis and etiology of these conditions. The pattern of presbyacusis and cortical deafness is discussed also. AIDS must be considered as a new cause of acquired central auditory dysfunction. PMID- 1748577 TI - [Binaural evoked brain stem potentials. Effect of sound direction on inferior colliculus response]. AB - Auditory evoked brain-stem responses were recorded using binaural stimulation on 12 test subjects. Rotation of the sound source in the horizontal plane was simulated digitally using a binaural mixing console. Binaural processing in the inferior colliculus was thus demonstrated in humans. The amplitude of the inferior colliculus response depends in an almost linear manner on sound direction and presents a typical directionality. While the amplitude is considered an important central code of sound direction, response latency of the inferior colliculus is controversial. The results confirm neuronal mechanisms which had been established by animal experiments for single units of the inferior colliculus and the auditory cortex. PMID- 1748578 TI - [Changes in early auditory evoked potentials in acoustic neuroma]. AB - The auditory brain-stem responses (ABRs) of 38 patients with acoustic neuroma (AN) were recorded pre-operatively and evaluated with regard to pathological deviations from the normal. Several qualitative and quantitative features of the ABRs were compared statistically with the results obtained from a control group for age and sex, and considering patients with various cochlear pathologies (Meniere's disease, sudden deafness, presbycusis). Retrocochlear disorders were ruled out by computed tomography or magnetic resonance imaging. Statistical analysis yielded the following results. The central conduction time (latency difference between Jewett waves J1 and J5) is significantly prolonged in the AN group. A critical value of 4.3 ms separates the retrocochlear from the cochlear lesions, with a sensitivity and specificity of 90%. If conductive hearing loss can be excluded, and if the amount of cochlear hearing loss is taken into account, about the same separation effectively is achieved by evaluation of the sole latency of J5 and its stimulus level dependence. The interaural difference of the central conduction time can be a useful parameter for indicating the presence of acoustic tumours, unless both sides are affected. The same is true of the interaural differences for the J5 latency, but this quantity must be corrected for the effects of peripheral hearing loss. The critical interaural difference values are 0.3 ms for the conduction time (at any stimulus level) and 0.5 ms for the latency of J5 (for stimulus levels above 60 dB nHL). A weaker distinction is provided by the amplitude of J5 and the amplitude ratio of J5 and J1. These quantities are only slightly smaller in cases of AN. Only the combination of small J5 amplitudes with large latency values can be regarded as being characteristic of retrocochlear lesions. This can be highlighted in an amplitude-latency diagram. Further hints as to the site of the lesion can be obtained from a distorted waveform morphology and from an abnormally large distance between hearing threshold and response threshold. The combined evaluation of all these features optimizes the effectivity of ABRs as a powerful tool in the diagnosis of retrocochlear disorders, but some false-positive and false-negative results cannot be excluded entirely. PMID- 1748579 TI - [Effect of venting the ear mold on speech discrimination in masking noise]. AB - In this study the importance of in situ measurement during the fitting of a hearing aid is clearly emphasized. Reliable evaluation of the real ear gain can be achieved only with this method, and hence the assessment of the advantages of earmold modifications on the hearing aid. In particular, the gain can be evaluated by the person fitting the aid. The insertion of a vent into an earmold raises the listening comfort of the hearing-impaired person. The speech intelligibility in background noise may also improve. We analysed the effect of earmold venting on speech intelligibility under different background noise conditions. We found that venting improves the speech intelligibility, especially in background noise simulating modulated speech. Our example clearly demonstrates the importance of an exact control of the hearing aid fitting by the physician. In one case a vent ended at the ear canal wall so that no improvement of hearing comfort could be expected. A new earmold was made and the effect on insertion gain was demonstrated when enlarging the vent step by step. PMID- 1748580 TI - [Idiopathic facial paralysis and magnetic resonance tomography (MRT)]. AB - We investigated 15 patients with unilateral facial paralysis using gadolinium(Gd) DTPA (diethylenetriamine pentaacetic acid) enhanced (magnetic resonance imaging (MRI). Eleven were idiopathic and 1 each was due to basal skill trauma, Lyme's disease, Foville's syndrome and herpes zoster oticus. Ten of 11 Bell's palsies showed a significant enhancement of the facial nerve on the paralysed side. In all cases enhancement was shown in the labyrinthine segment, in 9 in the meatal segment, in 8 in the mastoid segment and in 7 in the tympanic segment also. Follow-up Gd-enhanced MRI investigation was performed 3-11 months later in 8 patients. In 1 case with incomplete return of function after 3 months MRI enhancement was decreased. We could not find any correlation between the intensity of the Gd enhancement and the course, severity or outcome of Bell's palsy, or stapedius reflex audiometry. The mechanisms and aetiology of the Gd enhancement in Bell's palsy seem to be non-specific phenomena which are also found in post-traumatic facial lesions, for instance. Nevertheless, the ability to image the facial nerve in Bell's palsy provides a new means of examination in this disorder. In our opinion Gd-enhanced MRI is recommended in cases of recurrent or "atypical" Bell's palsy and in cases with total loss of electrical excitability, to exclude tumours. It is further suggested that MRI may provide valuable information concerning areas which may require surgical exploration or decompression. PMID- 1748581 TI - Training physicians to be doctors--teachers and healers, problem-solvers and decision-makers. AB - With the scientific advances made in medicine during the past 200 years, the training of physicians in America has changed from that of a mentor/apprenticeship relationship to one in which students are part of an impersonal, mass production process. From a historical perspective, it is contended that basic science and rote memorization of medical theory have subsumed the art of medicine. As a result, students are overloaded with irrelevant facts, few of which they carry over in their professional practice of medicine. To alter this teaching approach and, hence, the quality of physicians, medical school curricula should incorporate recommendations found in the General Professional Education of Physicians Report, among other sources. These recommendations, which have been incorporated successfully in the curriculum at the University of New Mexico School of Medicine, for example, include: establishing goals that may be coordinated interdepartmentally; reestablishing the physician/mentor for each student; using a small-group, interactive, problem solving, clinically oriented approach to teaching; measuring each student's ability to not only retain knowledge but, more importantly, apply such information to actual clinical problem-solving and decision-making situations; admitting liberal arts graduates--not premedical students--to medical schools; and recruiting and training faculty members who have the time to each and the ability to emphasize biomedicine rather than their special discipline. These changes will make students more than physicians. They will be "real doctors," individuals who not only possess knowledge but can apply it in their daily practice of medicine. PMID- 1748582 TI - Controlling systolic hypertension effectively and economically. PMID- 1748583 TI - A tissue pressure model for palpatory perception of the cranial rhythmic impulse. AB - A tissue pressure model was developed to provide a possible physiologic basis for the manifestation of the cranial rhythmic impulse (CRI). The model assumes that the sensation described as the CRI is related to activation of slowly adapting cutaneous mechanoreceptors by tissue pressures of both the examiner and the subject, and that the sources of change in these tissue pressures are the combined respiratory and cardiovascular rhythms of both examiner and subject. The model generates rhythmic impulses with patterns similar to those reported for the CRI. Also, a significant correlation was found between frequencies calculated from the model and published values for CRI obtained by palpation. These comparisons suggest that the CRI may arise in soft tissues and represents a complex interaction of at least four different physiologic rhythms. PMID- 1748584 TI - Fine needle aspiration. AB - The evolution of fine needle aspiration in the United States over the past three decades has overcome the initial concerns of clinicians regarding the accuracy of diagnosis and the potential for disseminating malignancy through the needle tract. The team approach, constant communication between interpreter and clinician, and acquisition of experience minimize the occurrence of false negative and false-positive results. The procedure is simple and easy to perform, it is safe with rare exceptions, it has patient acceptance, and it has unlimited application in the practice of medicine and patient evaluation. PMID- 1748585 TI - Influence of lateralized neuropsychological activities with and without sensorimotor components on EEG spectral power (alpha-rhythm). AB - Spectral analysis of the EEG (alpha-rhythm) was studied in 8 young right-handed men who underwent 6 experimental tasks which were compared with rest, and included two pure motor activities using only the right and then the left hand, two pure neuropsychological tasks, and two "mixed" tasks with both neurophysiological and motor activities. The electrophysiological parameters studied were the log of spectral power and an asymmetry index (RP-LP)/(RP + LP). In order to demonstrate lateralization of the EEG, one must associate lateralized motor and neuropsychological tasks (which are supposed to preferentially involve one of the cerebral hemispheres). These results may reconcile apparently divergent views published in the literature with respect to lateralized EEG modifications associated with cognitive activities. PMID- 1748586 TI - Heart rate, anxiety, anger, and arousal reactions to enforced time-wasting: dependence on reactive uncontrol, work involvement, and dominance factors of 'type A'. AB - The factor structure of 'Type A' was examined in an experiment derived from the observation of Frankenhaeuser et al. (1980) that 'Type A' people are abnormally 'aroused' when deprived of work. Questionnaire scales were used which dissected 'Type A' (based on replicated factor analyses). The sample statistics for 21 female volunteers approximated the parent population statistics on orthogonal scales of Work Involvement (WI), Reactive Uncontrol (RU) and Dominance (D). The laboratory session involved reading for 15 min: (a) self-chosen 'useful' work material and (b) material judged by subjects (Ss) to be 'useless'. Ss and trained observers used the same scales for rating anxiety, arousal and anger states during reading periods. Observers interpreted facial expressions from video tapes. Finger pulse amplitude and tonic heart rate (HR) were recorded during reading periods. RU (but not WI or D) correlated negatively with HR level and positively with increases in both HR and observed arousal under time-wasting conditions. Combination of changes in HR and observed arousal in a multiple R gave optimum 'prediction' of RU. While much evidence supported Frankenhaeuser's (1980) hypothesis, the multifactorial nature of 'Type A' was demonstrated. PMID- 1748587 TI - Empirical evidence against the 'cycle time dependency' assumption. AB - The interpretation of the 'cardiac cycle time effect', also named 'time-dependent primary bradycardia' by the Laceys, who first observed it, has been controversial in psychophysiology. Unconfounded evidence for the dependence of a vagal effect of psychological stimuli on time of stimulation within the cardiac cycle has been missing to date. An experiment in which the subjects could not anticipate the occurrence of the stimuli (short tones of a specific frequency that had to be counted) was performed. The data reduction procedure secured unambiguous interpretation of the data with respect to time-dependency or no time-dependency. No indication of any kind of cycle time dependency of the vagal effect was found. PMID- 1748588 TI - Autonomic, neuroendocrine, and subjective responses to emotion-inducing film stimuli. AB - The aim of the present study was to investigate differential emotional response patterns to film stimuli by multimodal assessment of subjective, autonomic and endocrine variables. Scenes of two films, chosen to induce different affective states, were presented to 20 male subjects. Changes in mood and perceived bodily sensations, autonomic activity (heart rate and skin conductance) and one endocrine parameter (salivary cortisol) were measured. Analyses revealed that the films elicited differential mood patterns. The cartoon film, which induced a pleasant, amused state, was accompanied by very few changes in bodily sensations, a temporary decrease in heart rate, and a rapid decrease in electrodermal activity. The suspense film, which elicited a marked reduction in joyfulness and relaxation together with an enhancement in irritation, differed from that pattern primarily by marked changes in several bodily sensations, an increase in electrodermal activity, and a temporary decrease in heart rate. There were no film-dependent cortisol changes. The results together with evidence from other emotion induction experiments support the usefulness of film segments in eliciting mild to moderate affective states and their concomitances. They particularly point to the relevance of bodily sensations as an emotional response component. PMID- 1748589 TI - Specific respiratory patterns distinguish among human basic emotions. AB - Prototypical respiratory-facial-postural actions ('emotional effector patterns') related to six basic emotions had been extracted from an ensemble of physiological reactions present in subjects reliving intense emotional situations (Bloch & Santibanez, 1972). Subjects reproducing these actions could evoke the corresponding subjective experience, which suggested their use as an experimental model for generating controlled emotional states. The aim of the present study was to quantify the respiratory parameters which characterize the emotions of joy laughter, sadness-crying, fear-anxiety, anger, erotic love and tenderness. Respiratory movements and facial/postural expressions were recorded from 36 young actors who had learned in previous workshops to express these emotions by reproducing the corresponding prototypical actions. A qualitative analysis of the recordings showed that as the emotional reproduction went along, both breathing and expression evolved from an initial 'robot-like' phase to a more natural stage in which spontaneous vocalizations and gestures appeared. This suggested a partial activation of the emotional network. The quantitative analysis of the respiratory movements for the fundamental cycles showed that for anger, erotic love and tenderness significant changes in amplitude, rate and duration of the 'expiratory pause' were the major elements of differentiation, while for sadness, joy and fear inspiratory over expiratory time ratios were the elements of differentiation. These last three emotions were further characterized by small amplitude/high rate saccadic respiratory movements superposed to different phases of the fundamental cycles. It is concluded that quantitatively well differentiated sets of respiratory changes characterize each of six basic emotions. The bottom-up experimental model for generating such emotions based on the joint activation of the respiratory-facial-postural systems and its relation to corresponding 'real-life' emotions is discussed. PMID- 1748590 TI - Event-related potentials to irrelevant deviant motion of visual shapes. AB - Event-related potentials to visual shapes moving across the visual field were recorded from 10 subjects. The subjects had to respond to the appearance of one of the shapes, while other shapes were irrelevant. On the periphery some of the shapes changed their orientation or their form. Sometimes the direction of movement was different from the standard direction. Subjects did not detect the changes of the pattern on the visual periphery, and the ERPs to these non detected deviants were identical to the ERPs to the standard stimuli. Six subjects detected the irrelevant direction of movement. In these subjects the deviant direction of motion elicited a fronto-central positive wave (P3s) with 322 ms mean latency. There was no such sharp positive peak in the four subjects who did not detect the deviant direction of movement. Unlike the non-target stimuli, the targets elicited a large positive wave (P3b) with 530 ms mean latency. PMID- 1748591 TI - HGM1: a research-oriented portable heart rate and galvanic skin response monitor. AB - A convenient portable recording device, HGM1, which allows digital field recording of skin conductance and heart rate data with laboratory levels of precision, is described. Examples of individual data are provided from a study of orienting response habituation, and from students participating in a study of examination anxiety, recorded while they sat scheduled class examinations. These illustrate the potential value of the device in field studies. PMID- 1748592 TI - Impaired eye tracking performance in patients with presenile onset dementia. AB - Smooth pursuit eye movements, saccades and eye blinks were electrooculographically recorded from 26 healthy subjects of different age and 35 patients with presumptive presenile onset dementia (mean age 54), who had to track a light spot which oscillated with different speeds. Older subjects (mean age 51) performed the eye tracking with less accuracy and more saccades than younger ones (mean age 22). 16 patients with stage CDR 1 according to Washington University Clinical Dementia Rating performed smooth pursuit eye movements significantly worse with increased saccade numbers than the healthy older subjects and lost attention significantly more often which was measured by omitted trackings to presented target oscillations. Their number of eye blinks was partly increased. The test is found suitable for early diagnosis of dementia onset, supporting clinical findings and presumptive diagnosis by objective parameters. PMID- 1748593 TI - Heartbeat perception, instructions, and biofeedback in the control of heart rate. AB - The present study was designed to examine the possibility that individual differences in heartbeat perception and instructions to control heart rate (HR) may influence the acquisition of voluntary control. Good (n = 20) and poor (n = 20) perceivers of cardiac activity were selected on the basis of their performance according to Whitehead et al. (1977) heartbeat discrimination procedure. Measures of state and trait anxiety (the State-Trait Anxiety Inventory Form X-1 and Form X-2) and Tellegen's Absorption Scale (TAS) were used to assess emotionality and absorptive ability. Good and poor heartbeat perceivers (a) were given non-motivating instructions to try to either increase or decrease their heart rate (HR) with, or (b) without the use of HR-feedback, and (c) were given motivating instructions to try to either increase or decrease their HR with, or (d) without HR-feedback. Heart rate, skin conductance (SC), and EMG activity were monitored. Subjects were also requested to indicate the cognitive strategies used during their HR control training. No relationship between heartbeat perception and state-trait anxiety measures was found. The results did not support the idea that individual differences in heartbeat perception are related to individual differences in HR-control. They did indicate, however, that motivating instructions improve the capacity to increase or decrease HR. Subjects were able to voluntarily increase or decrease their HRs with or without a feedback signal. However, more pronounced HR increases were obtained in the feedback as compared with the no-feedback condition. SC and EMG activity were in accordance with arousal levels demanded by HR decrease and increase tasks. Subjects used cognitive strategies concerning activation responses during HR-increase and relaxation responses during HR-decrease conditions. PMID- 1748594 TI - EEG alpha-wave in the visual cortex: check of the hypothesis of the scanning process. AB - In computer-controlled experiments the recognition by seven human observers of tachistoscopically presented geometrical figures of different size (from 0.5 to 9 angular degrees) or of different eccentricity (from 3 up to 16 degrees) in the visual field was studied. The onset of figures presentation coincided with different phases of the EEG alpha-wave in the occipital region. According to the criterion of an increase of recognition probability, an inverse dependence was revealed between the distance of the figures contour from the gaze (up to 9 degrees) and the succession of phases of alpha-wave. Small or more centrally localized figures were significantly better recognized when presented at relatively earlier phases of EEG alpha-wave, while bigger or relatively more peripherally localized figures - at earlier phases. At 16 degrees form the gaze no reliable dependence of recognition on the alpha-wave phases was revealed. The data obtained are discussed in connection with Pitts and McCulloch (1947) hypothesis about a periodical (with alpha-wave frequency) scanning wave spreading over the visual cortex. Possibility of a synchronous excitability fluctuation in the whole visual cortex with alpha-rhythm frequency that imitated the spreading process is also discussed. Data obtained and simulation of the mentioned possibilities confirmed the first explanation and thus confirmed Pitt's and McCulloch's ideas on the EEG alpha-wave as a reflection of the scanning process in the visual cortex. PMID- 1748595 TI - Motor imagination--a model for motor performances? AB - The effect of training competition (TC) on central nervous activation was investigated in order to examine whether motor imagination could serve as a model for complex motor skills concerning information processing and motor control. EEG was recorded before and immediately after the TC. The mean alpha frequency (MAF) was computed from the EEG power density spectra. A significant increase of MAF was found after the TC. Similar changes were found during motor imagination. Thus, motor imagination seems to be a good model to examine activation processes. PMID- 1748596 TI - Generalization of cardiovascular response: supportive evidence for the reactivity hypothesis. AB - Cardiovascular responses were monitored while 36 subjects completed a battery of laboratory stressors comprising mental arithmetic, a reaction time task, a speech task, and the forehead cold pressor. Inter-task consistency was assessed for each of 6 physiological parameters for all task pairings. Considerable inter-task consistency for reactivity scores was seen among the psychological stressors for all variables. The question of such consistency between the cold pressor and the psychological tasks was then addressed. The pattern of consistency was not as clear-cut in this case. For systolic blood pressure and pre-ejection period, reactivity scores to the cold pressor did not correlate with those to any of the psychological tasks. In contrast, cardiac output and total peripheral resistance responses showed considerable consistency. The importance of determining the nature of the relationship between psychological and physical stressors is discussed. PMID- 1748597 TI - Effects of stress management on blood pressure and other cardiovascular variables. AB - Blood pressure and impedance cardiography derived measures of heart rate, stroke volume, cardiac output and total peripheral resistance were measured in 16 persons before and after participation in a comprehensive program of stress management that included home monitoring of blood pressure and feedback of finger skin temperature during relaxation. Ten of the subjects were hypertensive and six were normotensive. Baseline measures of systolic and diastolic blood pressure and heart rate decreased significantly after participation in the program. In addition, reactivity to a psychological stressor (oral quiz) was significantly lower as revealed in reduced systolic and diastolic pressure, heart rate and cardiac output at the second assessment. A reduction in sympathetic nervous system activity is postulated as a possible mechanism for the changes observed. PMID- 1748598 TI - P300 from auditory and somatosensory stimuli: probability and inter-stimulus interval. AB - The P300 (P3) event-related brain potential (ERP) was elicited with auditory and somatosensory stimuli using an easy discrimination task in two experiments. Experiment 1 manipulated target stimulus probability (0.20 vs. 0.80). Experiment 2 manipulated inter-stimulus interval (2 s vs. 6 s) for both stimulus modalities in different conditions while keeping target probability constant. Probability and inter-stimulus interval had similar effects for auditory and somatosensory stimuli, with lower probability and longer inter-stimulus intervals producing larger P3 amplitudes. No statistically reliable differences in scalp distribution between modalities were obtained, with both modalities producing maximal amplitudes at Pz. The results suggest that auditory and somatosensory stimuli when used in a relatively easy discrimination task yield the same overall P3 values. PMID- 1748599 TI - Effects of mental countermeasures on psychophysiological detection in the guilty knowledge test. AB - This study focused on the effects of mental countermeasures on psychophysiological detection in a guilty knowledge paradigm. Two experiments which utilized a 3 x 2 between subjects factorial design were conducted. Two types of mental countermeasures (specific dissociations from the relevant stimulus and continuous dissociation throughout the entire test, as well as a control-no countermeasure condition were used). Each group was further subdivided into two conditions--a high attention condition created by motivational instructions and a deceptive verbal response to the relevant question; and a low attention condition in which no motivational instructions were provided and no verbal response was required. The results of both experiments (one was conducted in a field set up, and the other utilized more standard experimental equipment and measurement procedures) revealed the following pattern: the item-specific countermeasures tended to increase psychophysiological detection, whereas the continuous dissociations tended to decrease detection efficiencies. The pattern was consistent across attention conditions and experiments but it was stronger in the field experiment where overall detection efficiency was relatively high. In other respects the present results replicated previous findings and revealed a significant effect for the attention factor. PMID- 1748600 TI - Is your practice a drug-free workplace? PMID- 1748601 TI - Drug and alcohol abuse can affect your practice. PMID- 1748602 TI - Relevance of social science to veterinary medicine. PMID- 1748603 TI - Attitudinal survey of Tennessee beef producers regarding evacuation during an emergency. PMID- 1748604 TI - Underachiever's guide to building a small clientele. PMID- 1748605 TI - Practitioner's mid-life crisis. PMID- 1748606 TI - Clinical evaluation of 1% cyclosporine for topical treatment of keratoconjunctivitis sicca in dogs. AB - Keratoconjunctivitis sicca (KCS) is a prevalent and often vision-threatening condition in dogs. In several reports, 2% cyclosporine (cyclosporin A, CsA) was described as effective in modulating the clinical signs of KCS. This study was designed to compare the efficacy of 1% CsA vs a placebo, using a randomized double-blind clinical trial. Topical administration of 1% CsA significantly improved Schirmer wetting values and subjective markers of corneal health as compared with the placebo. In the dogs treated with topical administration of 1% CsA, the clinical signs of KCS were improved in 81.8% of cases. PMID- 1748607 TI - Topical administration of cyclosporine for treatment of keratoconjunctivitis sicca in dogs. AB - Sixty dogs with chronic keratoconjunctivitis sicca were treated by topical administration of 2% cyclosporine twice daily. Causes and duration of keratoconjunctivitis varied. Tear production improved in 75 of 100 eyes, and corneal pigmentation decreased in 45 of 67 eyes. Six factors were evaluated to determine their influence on treatment outcome. The only significant variable was the initial Schirmer tear test value. Side effects were few. Evidence of burning in response to application of cyclosporine resolved with change in the formulation of the topical solution. PMID- 1748608 TI - Reciprocal apparatus dysfunction as a cause of severe hind limb lameness in a horse. AB - A 2-year-old Appaloosa mare was admitted because of acute, severe hind limb lameness (grade 4 of 5). The hock could be flexed or extended without influencing the position of the stifle joint, and the fetlock and proximal interphalangeal joints could be extended while the hock was maintained in flexion. The diagnosis was functional loss of the reciprocal apparatus. The differential diagnoses for functional loss of the reciprocal apparatus include disruption of the common calcaneal tendon, the gastrocnemius muscle, the peroneus tertius, or the superficial digital flexor muscle. In this horse, the diagnosis was disruption of the superficial digital flexor muscle. The horse made an excellent recovery following 5 months of stall confinement. PMID- 1748609 TI - Anterior uveal melanoma, with secondary keratitis, cataract, and glaucoma, in a horse. AB - Intraocular melanoma was diagnosed in a 13-year-old horse. Secondary clinical findings included keratitis, cataract, and glaucoma. The eye was enucleated. Follow-up information did not give an indication of metastatic disease. PMID- 1748610 TI - Tarsocrural joint luxation in a horse. AB - A 14-year-old Quarter Horse x Thoroughbred gelding was admitted to the teaching hospital because of inability to bear weight on its right hind limb, associated with a severe deviation of the tarsus. The provisional diagnosis was tarsal joint luxation or fracture. Radiography revealed complete luxation of the tarsocrural joint. The luxation was reduced, using minimal force. The horse was confined to a box stall and was maintained in a full-length hind-limb cast for 33 days. Box stall confinement was continued for 3 months after removal of the cast. On reexamination 18 months after the injury, the horse had only mild lameness (grade 1 of 5), but had marked reduction in the range of motion of the tarsus. Radiography revealed extensive changes indicative of severe degenerative joint disease. The horse was still used occasionally as a light pleasure riding horse and maintained itself on pasture well. PMID- 1748611 TI - Thoracolumbar vertebral osteochondroma in a young dog. AB - Osteosarcoma was diagnosed in a 7-month-old female German Shepherd Dog with hind limb paresis. Radiography revealed a circumscribed calcified mass in the dorsal vertebral lamina at T13-L1 resulting in extradural compression of the spinal cord. Surgical excision of the mass resulted in gradual return to normal neurologic function. Four weeks after surgery, the dog became severely atactic after rolling onto its back. A chip fracture of T13 was identified, and the dog was euthanatized at the owners' request. PMID- 1748612 TI - Osteogenic sarcoma and cisplatin chemotherapy in dogs: 16 cases (1986-1989). AB - Sixteen dogs, given adjuvant cisplatin chemotherapy after amputation for osteogenic sarcoma of the appendicular skeleton, had a median survival time of 413 days. Ten dogs (62%) were alive 1 year after amputation. Dogs were given cisplatin at a dosage of 50 mg/m2 of body surface every 4 weeks for a total of 6 cisplatin treatments, or until metastatic disease was detected. Cisplatin chemotherapy was well-tolerated by most dogs, with only 1 dog developing serious gastrointestinal toxicosis, requiring hospitalization. Results of this study support other investigators' findings that when a cisplatin chemotherapy-based protocol is administered, survival times after amputation can be prolonged for dogs with osteogenic sarcoma. PMID- 1748613 TI - Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989). AB - The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions. PMID- 1748614 TI - Myiasis in two box turtles. AB - Two eastern box turtles (Terrapene carolina carolina) were treated for myiasis caused by Sarcophaga cistudinis. The tortoises were examined because of swellings of the proximal cervical regions. Both fully recovered following surgical removal of multiple larvae. PMID- 1748615 TI - Suspected lead toxicosis in a captive goshawk. AB - Lead toxicosis was diagnosed in a 3-week-old male goshawk after evaluation of the history, clinical signs, radiographic lesions, and laboratory values. Treatment with Ca-EDTA and supportive measures was successful. The presumed source of lead was from birds that had been shot with a pellet gun and used for food. PMID- 1748616 TI - What is your diagnosis? Benign bone cyst in the distal portion of the left femur. PMID- 1748617 TI - Do injection site reactions induce fibrosarcomas in cats? PMID- 1748618 TI - Reassures that academia values interdisciplinary cooperation. PMID- 1748619 TI - Exploring llama reproduction. PMID- 1748620 TI - Legionella pneumophila in a human trophoblast cell line. PMID- 1748621 TI - Epidermal growth factor, DNA synthesis and human hepatocytes. PMID- 1748622 TI - Insect muscle cell line forms contractile tissue networks in vitro. PMID- 1748623 TI - Different survival of continuous cell lines transported in live or frozen form. PMID- 1748624 TI - Culture of fetal alveolar epithelial type II cells in serum-free medium. AB - A serum-free culture medium (defined medium = DM) was elaborated by adding to Eagle's minimum essential medium (MEM), non-essential amino acids, transferrin, putrescine, tripeptide glycyl-histidyl-lysine, somatostatin, sodium selenite, ethanolamine, phosphoethanolamine, sodium pyruvate, and metal trace elements. This medium was tested for its ability to support sustained surfactant biosynthesis in fetal alveolar epithelial type II cells. For up to 8 days, ultrastructure was maintained with persistence of lamellar inclusion bodies. Thymidine incorporation into DNA was enhanced about 50% in DM as compared with MEM, whereas it was enhanced 300% in 10% fetal bovine serum. With DM, the incorporation of tritiated choline into phosphatidylcholine (PC) of isolated surfactant material was about twice that with MEM. Deletion experiments evidenced the prominent role of pyruvate, transferrin, and selenium in the stimulation of surfactant PC biosynthesis. The addition of biotin to DM enhanced surfactant PC biosynthesis slightly and nonsurfactant PC biosynthesis markedly. The presence of nucleosides seemed unfavorable to the synthesis of surfactant PC. Type II cells responded to the addition of epidermal growth factor and insulinlike growth factor-I both by increased thymidine incorporation into DNA and choline incorporation into PC. It is concluded that DM represents a useful tool for cultivating type II cells without loss of their specialized properties and for studying the regulation of cell proliferation and surfactant biosynthesis in a controlled environment. PMID- 1748625 TI - Induction of metamorphosis by thyroid hormone in anuran small intestine cultured organotypically in vitro. AB - We have developed an organ culture system of the anuran small intestine to reproduce in vitro the transition from larval to adult epithelial form which occurs during spontaneous metamorphosis. Tubular fragments isolated from the small intestine of Xenopus laevis tadpoles were slit open and placed on membrane filters in culture dishes. In 60% Leibovitz 15 medium supplemented with 10% charcoal-treated serum, the explants were maintained in good condition for at least 10 days without any morphologic changes. Addition of triiodothyronine (T3) at a concentration higher than 10(-9) M to the medium could induce cell death of larval epithelial cells, but T3 alone was not sufficient for proliferation and differentiation of adult epithelial cells. When insulin (5 micrograms/ml) and cortisol (0.5 microgram/ml) besides T3 were added, the adult cells proliferated and differentiated just as during spontaneous metamorphosis. On Day 5 of cultivation, the adult cells rapidly proliferated to form typical islets, whereas the larval ones rapidly degenerated. At the same time, the connective tissue beneath the epithelium suddenly increased in cell density. These changes correspond to those occurring at the onset of metamorphic climax. By Day 10, the adult cells differentiated into a simple columnar epithelium which possessed the brush border and showed the adult-type lectin-binding pattern. Therefore, the larval epithelium of the small intestine responded to the hormones and transformed into the adult one. This organ culture system may be useful for clarifying the mechanism of the epithelial transition from larval to adult type during metamorphosis. PMID- 1748626 TI - Differential stabilization of cytochrome P-450 isoenzymes in primary cultures of adult rat liver parenchymal cells. AB - Cytochrome P-450 dependent hydroxylation of testosterone was measured in 7-day old cultures of primary rat liver parenchymal cells. Determinations were carried out in monocultures of parenchymal cells and co-cultures of parenchymal cells with rat liver nonparenchymal epithelial cells, or mouse embryo fibroblasts. In the monoculture system, testosterone metabolism was drastically reduced and hardly measurable after 7 days in culture. In the co-culture systems, individual P-450 isoenzymes were stabilized on different levels. P-450s p and presumably c were well preserved, P-450 a was reduced but clearly measurable, P-450 h was totally lost whereas P-450s b and e were not measurable after 7 days (the activities of these isoenzymes however were already low in freshly isolated parenchymal cells). The results were independent of the cell line used for co cultivation and of the method of parenchymal cell isolation, that is whether collagenase or EDTA was used as the agent for dissociating the cells from the liver. The results showed that the co-cultivation of liver parenchymal cells with other nonparenchymal cells significantly improved the differentiated status of the former. In this cell culture system however, not every parameter was equally well stabilized. PMID- 1748627 TI - Organ culture as a model for investigating the effects of antimetabolites and nucleoside transport inhibitors on rodent colonic mucosa. AB - The in-vitro effects of hydroxyurea 5-FU and 5-FUdR have been extensively studied in experimental systems employing cell-line techniques. In this study we investigated the effects of these drugs on the levels of incorporation of labeled nucleosides into DNA in explants of intact rat colonic mucosa maintained in organ culture. The effects of the nucleoside transport inhibitors nitrobenzylthioinosine (NBMPR) and dipyridamole--which are modulators of antimetabolite cytotoxicity--on the incorporation of tritiated thymidine ([3H]TdR) into DNA were also studied. The incorporation of tritiated TdR into DNA was reduced by hydroxyurea but was not altered by either 5-FU or 5-FUdR. The levels of tritiated deoxyuridine were reduced by 5-FU and 5-FUdR in separate experiments; this is in keeping with thymidylate synthase inhibition. NBMPR and dipyridamole also reduced 3H-TdR incorporation into DNA. These results can be explained in terms of the known mechanisms of action of these drugs. This experimental model is therefore useful in assessing the effects of antimetabolites and nucleoside transport inhibitors in intact colonic mucosa. PMID- 1748628 TI - Adhesion, spreading, and proliferation of cells on protein carpets: effects of stability of a carpet. AB - In the present report we have investigated the role that the physical properties of substrata play in modulating the effects which components of extracellular matrix (ECM) exert on adhesion, spreading, and growth of retinal pigmented epithelial cells. By simple modifications of conditions for protein adsorption on glass we obtained a set of substrata all coated with proteins of ECM (protein carpets) but with different physical properties. Using these protein carpets we have shown that their stability (desorption rate) in tissue culture conditions varies according to the technique with which they were prepared. Both semiremovable and immobilized carpets are stable, whereas removable protein carpets desorb readily. Therefore, the protein concentration or composition or both may change with time in tissue culture depending on the technique used to prepare the carpet. In addition, efficacy of cell attachment to given protein may vary depending on whether a technique used to prepare the protein carpet involves denaturation of the protein. Adherent cells quickly remove (clear) weakly adsorbed protein carpets and it seems that the carpet removal is a mechanical process. During the carpet removal cells are rounded, which indicates that a spread cell phenotype normally associated with stress fibers and focal contacts occurs when the substratum is rigid enough to sustain cell traction. In addition, substrata lacking the rigidity to support the spread phenotype do not support cell proliferation either. PMID- 1748629 TI - Concomitant proliferation and formation of a stratified epithelial sheet by explant outgrowth of epidermal keratinocytes from adult mice. AB - A chemically defined medium containing 1.2 mM Ca2+ has been developed for the culture of primary epidermal keratinocytes from untreated adult mice such that proliferation is accompanied by the formation of desmosomes and stratification. Cultured cutaneous explants of 1 mm2 from the backs of untreated, control, and carcinogen-exposed mice all demonstrated epithelial outgrowth within 1 wk, and by 5 wk approached confluence with characteristics of terminal differentiation such as desmosomes and stratification. Addition of 12-O-tetradecanoylphorbol-13 acetate (TPA) to the medium in concentrations of 0.001, 0.01, and 0.1 micrograms/ml resulted in a delay of approximately 1 wk in the outgrowth of the explants compared with the acetone controls and in a 30% decrease in the diameter of the epithelial outgrowth at 3 wk. The inhibition in outgrowth was overcome at higher concentrations (0.5, 1.0, and 10 micrograms/ml TPA). No obvious differences in morphology or in the rate of epidermal outgrowth within a 5-wk interval among explants from normal untreated epidermis, epidermis from mice treated with acetone, or epidermis from mice treated with an initiating application of 7,12-dimethylbenz[a]anthracene were observed. The defined composition of this medium and its ability to support reproducibly and conveniently both proliferation and differentiation of normal as well as treated primary adult murine epidermal cells suggest that it should be useful for a number of studies not previously possible that are relevant to the biology of the skin, to toxicology, and to carcinogenesis in the murine model system. PMID- 1748630 TI - A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression. AB - The c-myc gene encodes a sequence-specific DNA-binding protein (c-Myc) that forms leucine zipper complexes and can act as a transcription factor. Growth factor stimulation of cells causes the phosphorylation of the c-Myc transcriptional activation domain at Ser62 within a proline-rich region that is highly conserved among members of the Myc family (Alvarez, E., Northwood, I.C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). This phosphorylation site is a substrate for growth factor-regulated MAP kinases and for the cell cycle-dependent protein kinase p34cdc2. We report that serum treatment of cells results in a marked increase in the transactivation of gene expression mediated by the c-Myc transcriptional activation domain. A point mutation at the site of growth factor-stimulated phosphorylation (Ser62) decreases the serum induction of transactivation. These data indicate that the c-Myc transcriptional activation domain may be a direct target of signal transduction pathways. PMID- 1748631 TI - The sequence of squash NADH:nitrate reductase and its relationship to the sequences of other flavoprotein oxidoreductases. A family of flavoprotein pyridine nucleotide cytochrome reductases. AB - Nucleotide sequences were determined for cDNA clones for squash NADH:nitrate oxidoreductase (EC 1.6.6.1), which is one of the most completely characterized forms of this higher plant enzyme. An open reading frame of 2754 nucleotides began at the first ATG. The deduced amino acid sequence contains 918 residues, with a predicted Mr = 103,376. The amino acid sequence is very similar to sequences deduced for other higher plant nitrate reductases. The squash sequence has significant similarity to the amino acid sequences of sulfite oxidase, cytochrome b5, and NADH:cytochrome b5 reductase. Alignment of these sequences with that of squash defines domains of nitrate reductase that appear to bind its 3 prosthetic groups (molybdopterin, heme-iron, and FAD). The amino acid sequence of the FAD domain of squash nitrate reductase was aligned with FAD domain sequences of other NADH:nitrate reductases, NADH:cytochrome b5 reductases, NADPH:nitrate reductases, ferredoxin:NADP+ reductases, NADPH:cytochrome P-450 reductases, NADPH:sulfite reductase flavoproteins, and Bacillus megaterium cytochrome P-450BM-3. In this multiple alignment, 14 amino acid residues are invariant, which suggests these proteins are members of a family of flavoenzymes. Secondary structure elements of the structural model of spinach ferredoxin:NADP+ reductase were used to predict the secondary structure of squash nitrate reductase and the other related flavoenzymes in this family. We suggest that this family of flavoenzymes, nearly all of which reduce a hemoprotein, be called "flavoprotein pyridine nucleotide cytochrome reductases." PMID- 1748632 TI - Oxalate decarboxylase from Collybia velutipes. Purification, characterization, and cDNA cloning. AB - The oxalate-degrading enzyme oxalate decarboxylase (EC 4.1.1.2), which is inducible by oxalic acid, was purified to homogeneity from a crude extract of Collybia velutipes, a basidiomycetous fungus. Two forms of the enzyme were resolved on chromatofocusing. The two isozymes were shown to be related by amino acid composition, peptide mapping, and immunological cross-reactivity. Peak A, eluting at pH 3.3, was used for further study; the Km was found to be 4.5 mM, and the Vmax was 166 mumol/min/mg. The subunit molecular mass of the glycosylated enzyme was 64 kDa, whereas the mass of the deglycosylated protein was 55 kDa. The enzyme showed an acidic pl, was very stable over a wide pH range, and was moderately thermostable. The cDNA encoding the enzyme was obtained by immunoscreening a lambda gt11 expression library. In vitro translation of hybrid selected mRNA gave a 55-kDa protein. Genomic Southern hybridization indicated the oxalate decarboxylase is encoded by a single gene. The cDNA probe hybridized to a single 1.5-kilobase pair species of mRNA. The mRNA was shown to be induced by oxalic acid. A temporal relationship between enzyme activity and mRNA levels was observed, thus suggesting that the expression of oxalate decarboxylase is regulated at the transcriptional level. PMID- 1748633 TI - Substantial increase of the inhibitory activity of Mirabilis antiviral protein by an elimination of the disulfide bond with genetic engineering. AB - Mirabilis antiviral protein (MAP) is a rigid, heat-stable protein composed of 250 amino acids with an intramolecular disulfide bond. MAP inhibits the in vitro protein synthesis of rabbit reticulocyte with approximately one-thirtieth the activity of the ricin A chain, a homologous protein with no such bond (Habuka, N., Murakami, Y., Noma, M., Kudo, T., and Horikoshi, K. (1989) J. Biol. Chem. 264, 6629-6637; Habuka, N., Akiyama, K., Tsuge, H., Miyano, M., Matsumoto, T., and Noma, M. (1990) J. Biol. Chem. 265, 10988-10992). The bond is presumed to induce some structural perturbation that alters the mode of interaction with the substrate ribosome and thus lowers the activity. To confirm this hypothesis, a mutant MAP gene in which the codons of both cysteines were replaced by those of serines was constructed and expressed in Escherichia coli, and its product (C36/22OS) was purified. In a sodium dodecyl sulfate-polyacrylamide gel electrophoresis, C36/220S showed the same mobility as that of MAP reduced by 2 mercaptoethanol, whereas nonreduced MAP showed faster migration. The inhibitory activity of C36/220S was approximately 22 times higher than that of native MAP, that is the mutant had an IC50 of 0.16 nM for the protein synthesis of the rabbit reticulocyte system, whereas the native MAP had an IC50 of 3.5 nM. The results indicate that the activity of MAP is increased by the elimination of the disulfide bond, and this supports the hypothesis. PMID- 1748634 TI - Metabolism of 5,6-epoxyeicosatrienoic acid by the human platelet. Formation of novel thromboxane analogs. AB - Radiolabeled cis-(+-)-5,6-epoxyeicosatrienoic acid (5(6)-EpETrE) was incubated with a suspension of isolated human platelets in order to study its metabolic fate. The epoxide slowly disappeared from the suspension and was completely metabolized within 30 min. After extraction and analysis by reverse-phase high performance liquid chromatography, seven metabolites were found. Addition of either indomethacin (0.01 mM, cyclooxygenase inhibitor) or BW755C (0.1 mM, cyclooxygenase/lipoxygenase inhibitor) to the incubations blocked the formation of four and six metabolites, respectively, 1,2-Epoxy-3,3,3-trichloropropane (inhibitor of microsomal epoxide hydrolase) failed to inhibit the formation of 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETrE), a hydrolysis product of the precursor 5(6)-EpETrE. The metabolites were characterized by UV spectroscopy, negative ion chemical ionization liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and, in one instance, coelution with synthetic standard. Three primary platelet metabolites were structurally determined to be 5,6-epoxy-12-hydroxyeicosatrienoic acid, 5,6-epoxy-12-hydroxyheptadecadienoic acid, and a unique bicyclic metabolite, 5-hydroxy-6,9-epoxy-thromboxane B1, which originated from intramolecular hydrolysis of 5,6-epoxythromboxane-B1. This thromboxane analog was partially separated into stereoisomers and coeluted with the racemic synthetic standard in gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Three other metabolites were characterized as 5,6,12-trihydroxyeicosatrienoic acid, 5,6,12-trihydroxyheptadecadienoic acid, and 5,6-dihydroxythromboxane-B1, and resulted from the hydrolysis of the corresponding epoxides rather than from the metabolism of 5,6-DiHETrE. The latter was not metabolized by platelet cyclooxygenase or lipoxygenase. The biosynthesis of two cyclooxygenase metabolites indicated the formation of unstable 5,6 epoxythromboxane-A1 as an intermediate precursor. Platelet aggregation was not induced by 5(6)-EpETrE, although responsiveness to arachidonic acid was reduced following preincubation with the epoxide. The platelet metabolites of 5(6)-EpETrE might be useful in assessing its in vivo production in humans. PMID- 1748635 TI - Oleic acid promotes changes in the subcellular distribution of protein kinase C in isolated hepatocytes. AB - The effect of oleate on the subcellular distribution of protein kinase C (PKC) was studied in isolated hepatocytes and in perfused rat liver in the presence of physiological concentrations of serum albumin. A time- and dose-dependent translocation of PKC from the cytosol towards the membranes was observed at oleate concentrations that fell within the range of concentrations reached under several physiological conditions. Analysis of the membrane-bound isoenzymes of PKC by hydroxylapatite chromatography revealed that the beta isoenzyme was preferentially translocated to this compartment in hepatocytes incubated with oleate. Activation of PKC after incubation of hepatocytes with oleate involved at least three different effectors of the enzyme: the fatty acid itself, the diacylglycerol synthesized from oleate, and the rise in the cytosolic calcium concentration elicited by oleate. As a result of PKC activation, protein phosphorylation of intact hepatocytes in response to oleate exhibited an enhancement in the phosphate content of a protein of 82 kDa, similar to that phosphorylated in the presence of phorbol dibutyrate. PMID- 1748636 TI - Skeletal myoblasts utilize a novel beta 1-series integrin and not alpha 6 beta 1 for binding to the E8 and T8 fragments of laminin. AB - The E8 fragment of laminin stimulates myoblast attachment and locomotion. Myoblast attachment to laminin/E8 was blocked by anti-integrin antibodies against beta 1-chains but not by antibodies against alpha 6-chains. By contrast, other cell lines (e.g. B16, HT1080, P19, F9, Pys2, 3T3, and 3T6) were blocked both by anti-beta 1 and anti-alpha 6. All cells tested also bound to approximately 125 kDa C-terminal fragments of E8 (T8 and T8'). Immunoprecipitation of surface iodinated myoblasts revealed beta 1-, alpha 3-, and alpha 5-integrin chains and a novel chain that co-precipitated with anti-beta 1 antibodies running at approximately 95 kDa (reduced). I125-alpha 6 beta 1 was immunoprecipitated from cells whose attachment to E8 was blocked by anti-alpha 6 antibodies. By contrast, little alpha 6 beta 1 could be immunoprecipitated from myoblasts. beta 1-Integrin and the novel alpha-chain (alpha'), Mr approximately 120,000/approximately 95.000 (nonreduced/reduced), from myoblast lysates were retained during affinity chromatography on Engelbreth-Holm-Swarm-laminin affinity columns. beta 1, alpha 1, and the novel alpha' were retained from Rugli cell lysates on Engelbreth-Holm Swarm-laminin columns. alpha 3 was not bound. When E8 was used as affinity matrix, only beta 1 and alpha' were retained. The N-terminal sequence of Rugli alpha' was homologous to alpha-chains of beta 1-series integrins and was most similar to alpha 6 (9 identical residues out of 14). However, there were distinctive differences; in particular, 2 residues were deleted in comparison with alpha 6. PMID- 1748637 TI - Drosophila 5 S RNA processing requires the 1-118 base pair and additional sequence proximal to the processing site. AB - Using an in vitro processing system, we have identified a required sequence surrounding the Drosophila melanogaster 5 S RNA processing site at nucleotide 120. Mutations in this region vary the processing rate from complete inhibition to a level equal to or greater than wild type. Analysis of mutants at +1 and in the region 118-122 separates the inhibitory effect into two parts. 1) Nucleotide 118 C, the base-paired nucleotide in helix I proximal to the processing site, plays an essential role. Changing it to a purine inhibits processing. The +1-118 base pair must be intact, but this alone is not sufficient for processing, since compensatory changes at +1 do not restore down-processing mutants at 118 to the wild type level. 2) The processing site has to be pyrimidine rich; multiple contiguous purines inhibit processing. On the other hand, multiple pyrimidines can largely negate the inhibitory effect of a mutation at position 118. Thus a base-paired C at 118 followed by a stretch of pyrimidines is the processing signal, which may be recognized by the processing enzyme and/or a required accessory factor. PMID- 1748638 TI - Transport of proteins into chloroplasts. Delineation of envelope "transit" and thylakoid "transfer" signals within the pre-sequences of three imported thylakoid lumen proteins. AB - The targeting of cytosolically synthesized proteins into the thylakoid lumen is mediated by an aminoterminal pre-sequence consisting of an "envelope transit" and a "thylakoid transfer" signal in tandem. We have investigated the structural characteristics of several thylakoid transfer signals by determining the intermediate sites at which the stromal processing peptidase cleaves to remove the transit sequences. Using this approach we have found that the thylakoid transfer signals of Silene pratensis plastocyanin, 23-kDa oxygen-evolving complex protein from wheat, and 33-kDa oxygen-evolving complex protein from wheat, are 25, 39, and 48 residues in length, respectively. All of the transfer signals contain hydrophobic core sequences and a "-3,-1" motif reminiscent of those found in signal sequences, but the amino-terminal regions of the transfer signals of the 23- and 33-kDa proteins are both longer and more highly charged. The net charge of each amino-terminal region of the transfer sequences is +1, including the amino-terminal amino group. In each case, the stromal processing peptidase cleaves immediately after a positively charged residue, but otherwise the cleavage sites exhibit no common elements of either primary or secondary structure. PMID- 1748639 TI - Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition, and phagocytosis. AB - Damaged or old erythrocytes are cleared rapidly from circulation. Because several common biochemical lesions can induce the clustering of integral membrane proteins, we have proposed that formation of microscopic protein aggregates in the membrane might constitute a cell surface marker that promotes removal of the defective/senescent cells. We demonstrate here that treatments that cluster integral membrane proteins in erythrocytes (1 mM ZnCl2, 1 mM acridine orange, and 0.35 microM melittin) induce autologous IgG binding, complement fixation, and phagocytosis by human monocytes in vitro. Removal of the clustering agents prior to incubation in autologous serum or cross-linking of cell surface proteins before addition of clustering agents prohibited the above response, while cross linking after treatment with the clustering agents preserved the response even if the clustering agents were later removed. Furthermore, subsequent reversal of the chemical cross-link maintaining the clustered distribution also reversed the induction of IgG binding, complement deposition, and phagocytosis. Finally, by deleting or inactivating different steps in the phagocytosis pathway, the chronology of steps was shown to be: (i) integral protein clustering, (ii) IgG binding, (iii) complement deposition, and (iv) phagocytosis. PMID- 1748640 TI - Regulation of agonist-induced prostaglandin E1 versus prostaglandin E2 production. A mass analysis. AB - Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2), derived by enzymatic oxidation of cellular dihomogammalinolenic acid (DHLA) and arachidonic acid (AA), respectively, have diverse and, at times, distinct biological actions. It has been suggested that PGE1 specifically inhibits a variety of inflammatory processes, and, in light of the potential therapeutic benefit of PGE1 and its fatty acid precursor in inflammatory disorders, there is growing interest in the biochemical mechanisms which determine the balance between PGE1 and PGE2 synthesis. Metabolic studies in this area have been hampered by the difficulties in measuring the extremely small masses of these prostaglandins which are generated in cell culture systems. We studied the regulation of PGE1 versus PGE2 synthesis using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Because EFD-1 cells contain no endogenous AA or DHLA, we were able to replete the cells with AA and DHLA of known specific activities; thus, the mass of both cellular AA and DHLA, and synthesized PGE1 and PGE2, could be accurately determined. The major finding of this study is that production of PGE2 was highly favored over production of PGE1 due to preferential incorporation of AA versus DHLA into, and release from, the total cellular phospholipid pool. Further, we correlated the selective release of AA versus DHLA from total cellular phospholipids with the selective incorporation of AA versus DHLA into specific phospholipid pools. In addition, we showed that conversion of DHLA to AA by delta 5 desaturase was enhanced by increasing the cellular mass of n-6 fatty acids and by increasing the cell proliferative activity. Together, these results indicate that the relative abundance of PGE2 versus PGE1 in vivo is not merely a function of the relative abundance of AA versus DHLA in tissues, but also relates to markedly different cellular metabolism of these two fatty acids. PMID- 1748641 TI - Proteolytic formation of either of the two prothrombin activation intermediates results in formation of a hirugen-binding site. AB - Hirugen, a synthetic dodecapeptide corresponding to the carboxyl-terminal amino acids 53-64 of hirudin, binds within a deep groove in thrombin that contains a cationic region referred to as the anion-binding exosite. This region is important in many of the binary interactions of thrombin with macromolecular substrates and cofactors. Fluorescein-labeled hirugen was used to probe which steps in the prothrombin activation process generate this anion-binding exosite. Two activation cleavage sites exist in bovine prothrombin. Cleavage at Arg274 Thr275 releases the activation fragments to generate the thrombin precursor, prethrombin 2. Cleavage of prothrombin within a disulfide loop at Arg323-Ile324 leads to formation of meizothrombin with no loss of peptide material but with formation of amidolytic activity. Cleavage of the same bond in prethrombin 2 generates thrombin. Hirugen, labeled at the amino terminus with fluorescein isothiocyanate, does not bind to prothrombin but does bind to thrombin (Kd = 9.6 +/- 1.2 x 10(-8) M), prethrombin 2 (Kd = 1.3 +/- 0.1 x 10(-7) M), thrombin fragment-2 complex (Kd = 1.1 +/- 0.2 x 10(-6) M), and meizothrombin (Kd = 1.6 +/- 0.5 x 10(-8) M). Prothrombin fragment-2 and hirugen both bind independently to thrombin. A ternary complex can form with hirugen and fragment-2 and either thrombin or prethrombin 2, suggesting that fragment-2 and hirugen bind to discrete sites. Hirugen also alters the active site conformation of thrombin as detected by modulation of synthetic substrate hydrolytic activity. These studies suggest that conformational changes, rather than alleviating steric hindrance, are responsible for the formation of the hirugen-binding site during prothrombin activation. Furthermore, this conformational change can be effected by the cleavage of either of the two bonds required for activation of prothrombin. PMID- 1748642 TI - Structural and functional consequences of amino acid substitutions in the second conserved loop of Escherichia coli adenylate kinase. AB - All known nucleoside monophosphate kinases contain an invariant sequence Asp-Gly Phe(Tyr)-Pro-Arg. In order to understand better the structural and functional role of individual amino acid residues belonging to the above sequence, three mutants of Escherichia coli adenylate kinase (D84H, G85V, and F86L) were produced by site-directed mutagenesis. Circular dichroism spectra revealed that the secondary structure dichroism spectra revealed that the secondary structure of all three mutant proteins is very similar to that of the wild-type enzyme. However, each of the substitutions resulted in a decreased thermodynamic stability of the protein, as indicated by differential scanning calorimetry measurements and equilibrium unfolding experiments in guanidine HCl. The destabilizing effect was most pronounced for the G85V mutant, in which case the denaturation temperature was decreased by as much as 11 degrees C. The catalytic activity of the three mutants represented less than 1% of that of the wild-type enzyme. Furthermore, for the D84H-modified form of adenylate kinase, the impaired binding of nucleotide substrates was accompanied by a markedly decreased affinity for magnesium ion. These observations support the notion that Asp84 is directly involved in binding of nucleotide substrates and that this binding is mediated by interaction of the aspartic acid residue with divalent cation. The two remaining residues probed in this study, Gly85 and Phe86, belong to a beta-turn which appears to play a major role in stabilizing the three-dimensional structure of adenylate kinase. PMID- 1748643 TI - Ligand recognition by influenza virus. The binding of bivalent sialosides. AB - Infection by influenza virus is initiated by a cellular adhesion event that is mediated by the viral protein, hemagglutinin, which is exposed on the surface of the virion. Hemagglutinin recognizes and binds to cell surface sialic acid residues. Although each individual ligand binding interaction is weak, the high affinity of influenza virus for cells that bear sialic acid residues is thought to result from a multivalent attachment process involving many similar recognition events. To evaluate such binding we have synthesized three series of compounds, each containing two sialic acid residues separated by spacers of different length, and have tested them as ligands for influenza hemagglutinin. No increased binding to the bromelain-released hemagglutinin ectodomain was seen for any of the bivalent compounds as determined by 1H NMR titration. In contrast, however, a spacer length between sialic acid residues of approximately 55 A sharply increases the binding of these bidentate species to whole virus as determined by hemagglutination inhibition assays. The most effective compound containing glycines in the linking chain displayed 100-fold increased affinity for whole virus over the paradigm monovalent ligand, Neu5Ac alpha 2Me. PMID- 1748644 TI - Complete structure of the glycan of lipopeptidophosphoglycan from Trypanosoma cruzi Epimastigotes. AB - The lipopeptidophosphoglycan is the major cell surface glycoconjugate of the epimastigote forms of the parasitic protozoan Trypanosoma cruzi. A detailed partial structure for this molecule has been reported (Previato, J. O., Gorin, P. A. J., Mazurek, M., Xavier, M. T., Fournet, B., Wieruszesk, J. M., and Mendonca Previato, L. (1990) J. Biol. Chem. 265, 2518-2526). In this study, we complete the primary structure assignments and describe the microheterogeneity found in the lipopeptidophosphoglycan glycan, using a combination of 1H and 31P NMR, fast atom bombardment mass spectrometry, methylation linkage analysis, and exoglycosidase sequencing. The lipopeptidophosphoglycan is a glycosylated inositol-phosphoceramide with striking homology to glycosylphosphatidylinositol membrane anchors found attached to a wide variety of plasma membrane proteins throughout the eukaryotes. PMID- 1748645 TI - Methylation patterns of the human apoA-I/C-III/A-IV gene cluster in adult and embryonic tissues suggest dynamic changes in methylation during development. AB - We describe here a detailed analysis of the methylation patterns of the apoC-III and apoA-IV genes in adult and embryonic tissues. Together with previously reported data on the human apoA-I gene (4), the results presented here constitute a comprehensive study on the methylation pattern of the apoA-I/C-III/A-IV gene cluster. The two genes (apoC-III and apoA-IV) display tissue-specific methylation patterns that correlate with their activity. This gene-specific methylation pattern indicates that the apoA-I/C-III/A-IV gene cluster is not one entity with respect to methylation. The cluster is almost entirely methylated in tissues that do not express any of the genes; however, individual gene regions are unmethylated in the tissue of expression. A comparison of the observed methylation patterns in adult tissues with those in embryonic tissues suggests that the mature tissue-specific methylation patterns are a result of an interplay between demethylation and de novo methylation events in the embryo. These changes in DNA methylation include demethylation in the early embryo followed by de novo methylation at later stages. A second round of tissue-specific demethylation and methylation de novo occurs in the late embryo as well. Evidence presented here supports the idea that CpG islands are protected in general from methylation de novo by a built-in signal and not by CpG density per se. PMID- 1748646 TI - Mobility of the terminal regions of flagellin in solution. AB - The mobility of the disordered terminal regions of flagellin was examined in detail based on 1H NMR chemical shifts and spin-lattice relaxation times in the rotating frame. Proteolytic fragments of flagellin with terminal deletions of different sizes were used to compare the dynamical properties of various N- and C terminal segments. We found that dynamic properties of different terminal segments were similar to each other and were close to those of the heat-denatured state of flagellin. The main chain of these terminal segments undergoes rapid motions with effective correlation times of 1.3-4.1 x 10(-9) s. The terminal regions contain no large segments with well-defined structure. However, comparison with the random-coiled state of poly-L-lysine suggests significant structural constraints in the terminal regions (as well as in the heat-denatured flagellin) which may reflect the existence of some highly fluctuating secondary structure, as suggested by earlier CD studies. PMID- 1748647 TI - Purification of solanesyl-diphosphate synthase from Micrococcus luteus. A new class of prenyltransferase. AB - The activity of solanesyl-diphosphate synthase from Micrococcus luteus is stimulated by a high molecular mass fraction (HMF) which is separated from cell free extracts of the same bacterium by DEAE-Toyopearl chromatography followed by Sephadex G-100 chromatography. By employing HMF in the assay procedure, solanesyl diphosphate synthase was able to be purified to homogeneity and was found to be a homodimer with a monomeric molecular mass of 34 kDa. In contrast to hexaprenyl- and heptaprenyl-diphosphate synthases, which are composed of two easily dissociable components that are inactive unless combined, the homogeneously purified solanesyl-diphosphate synthase itself showed a catalytic activity, though weak, catalyzing the synthesis of both (all-E)-nonaprenyl-(solanesyl-) and (all-E)-octaprenyl diphosphate. HMF does not affect the stability of solanesyl diphosphate synthase or Km values for isopentenyl diphosphate and farnesyl diphosphate, but it markedly increases Vmax values in a time-dependent manner. Several lines of evidence indicate that HMF contains a factor which binds to polyprenyl products and removes them out of the active site of enzyme to facilitate and maintain the turnover of catalysis. PMID- 1748648 TI - Two-dimensional NMR investigation of iron-sulfur cluster electronic and molecular structure of oxidized Clostridium pasteurianum ferredoxin. Interpretability of contact shifts in terms of cysteine orientation. AB - A two-dimensional NMR study has been carried out on the four-iron clusters of a bacterial oxidized ferredoxin for the purpose of investigating the relationship between contact shift patterns and the orientation of the individual coordinated cysteines. The ferredoxin from Clostridium pasteurianum, CpFdox, was selected because of its extensive sequence homology, and likely close structural similarity, to the crystallographically characterized ferredoxin from Peptococcus aerogenes, Pa Fdox (Adman, E.T., Sieker, L.C., and Jensen, L. H. (1973) J. Biol. Chem. 248, 3987-3996). Rapid data collection rates with minimal but adequate acquisition time allowed the detection of numerous CpFdox cross-peaks from the contact-shifted and strongly relaxed coordinated cysteinyl C beta H protons in the resolved 10-20 ppm window. Relatively strong magnitude COSY cross peaks from the resolved eight cysteinyl C beta H resonance unambiguously locate the geminal C beta H partner for each residue; weaker cross-peaks locate the C alpha Hs from three of the residues. The geminal nature of the magnitude-COSY detected partners to the resolved C beta H peaks is confirmed by strong NOESY cross-peaks. The NOESY spectra, moreover, assign an additional two cysteinyl C alpha H resonances. The present results confirm some previous one-dimensional NOE assignments, revise others, and locate resonances previously undetected (Bertini, I., Briganti, F., Luchinat, C., and Scozzafara, A. (1990) Inorg. Chem. 29, 1874-1880). A striking pairwise pseudo-symmetry in cysteinyl contact shift patterns is observed which is attributed to the previously recognized pseudo-symmetry in the crystal of PaFdox. A detailed analysis of the structural/electronic determinants of the coordinated cysteine C beta H contact shift pattern is made, and the NMR data necessary for unique interpretation are identified. It is shown that analysis of the relaxation properties of cysteine beta-methylene protons provides the stereospecific assignments necessary for comparison of shift ratios with crystallographic structural data. The available structural data on PaFdox (Backes, G., Mino, Y., Loehr, T., Meyer, T., Cusanovich, M., Sweeney, W., Adman, E., and Sanders-Loehr, J. (1991) J. Am. Chem. Soc. 13, 2055-2064) are qualitatively but not quantitatively consistent with the observed cysteinyl contact shift pattern, with the NMR data reflecting more asymmetry than previous studies. A tentative assignment of a single pair of symmetry-related cysteines is proposed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1748649 TI - The role of calcium in follicle-stimulating hormone signal transduction in Sertoli cells. AB - Sertoli cells are hormonally regulated by follicle-stimulating hormone (FSH) acting upon a G-protein-linked cell surface FSH receptor. FSH increases intracellular cyclic AMP but the involvement of other signal transduction mechanisms including intracellular calcium in FSH action are not proven. Using freshly isolated rat Sertoli cells we measured cytosolic free ionized calcium levels by dual-wavelength fluorescence spectrophotometry using the calcium sensitive fluorescent dye Fura2-AM. The cytosolic calcium concentration in unstimulated Sertoli cells was 89 +/- 2 nM (n = 151 experiments) and was markedly increased by either calcium channel ionophores (ionomycin, Bay K8644) or plasma membrane depolarization consistent with the presence of voltage-sensitive and independent calcium channel in Sertoli cell membranes. Ovine FSH stimulated a specific, sensitive (ED50, 5.0 ng of S-16/ml), and dose-dependent (maximal at 20 ng/ml) rise in cytosolic calcium commencing within 60 s to reach levels of 192 +/ 31 nM after 180 s and lasting for at least 10 min. The effect of FSH was replicated by forskolin, cholera toxin, and dibutyryl cyclic AMP, suggesting that cyclic AMP may mediate the FSH-induced rise in cytosolic calcium. The FSH-induced rise in cytosolic calcium required extracellular calcium and was abolished by calcium channel blockers specific for dihydropyridine (verapamil, nicardipine), nonvoltage-gated (ruthenium red) or all calcium channels (cobalt). Thus FSH action on Sertoli cells involves a specific, rapid, and sustained increase in cytosolic calcium which requires extracellular calcium and involves both dihydropyridine-sensitive, voltage-gated calcium channels and voltage independent, receptor-gated calcium channels in the plasma membranes of rat Sertoli cells. The replication by cyclic AMP of the effects of FSH suggests that calcium may be a signal-amplification or -modulating mechanism rather than an alternate primary signal transduction system for FSH in Sertoli cells. PMID- 1748650 TI - Translocation of HL-60 cell 5-lipoxygenase. Inhibition of A23187- or N-formyl methionyl-leucyl-phenylalanine-induced translocation by indole and quinoline leukotriene synthesis inhibitors. AB - We have demonstrated translocation of HL-60 cell 5-lipoxygenase to a membrane compartment in response to both the calcium ionophore A23187 and the receptor mediated stimulus, N-formyl-methionyl-leucyl-phenylalanine (fMLP). In addition, we have shown inhibition of A23187- and fMLP-induced 5-lipoxygenase translocation by an indole and a quinoline leukotriene synthesis inhibitor, MK-886 and L 674,573, respectively. Selectivity of inhibition of 5-lipoxygenase translocation in both fMLP- or A23187-challenged cells is shown using the indole L-583,916 and quinoline L-671,480, which neither inhibit leukotriene synthesis nor inhibit 5 lipoxygenase translocation. The present study in HL-60 cells is the first demonstration of the selective inhibition of 5-lipoxygenase translocation by quinoline leukotriene synthesis inhibitors, exemplified by L-674,573. Also described here is the first demonstration of 5-lipoxygenase translocation and inhibition in response to a stimulus other than A23187, namely the receptor mediated stimulus, fMLP. PMID- 1748651 TI - The phosphorylation and activation of B-raf in PC12 cells stimulated by nerve growth factor. AB - Treatment of PC12 cells with nerve growth factor does not alter the levels of B raf mRNA, but does induce rapid phosphorylation of B-raf proteins. Phosphorylation was observed after 1.5 min and reached a maximum by 10-15 min. B raf protein was phosphorylated almost exclusively on serine residues; no tyrosine phosphorylation was detected. Nerve growth factor-induced phosphorylation was not affected by depletion of protein kinase C or by removal of extracellular calcium but was inhibited by K-252a. Concomitant with the increase in serine phosphorylation, nerve growth factor treatment also increased the serine/threonine kinase activity of B-raf protein within 1-2 min. PMID- 1748652 TI - Differential regulation of protein kinase C isozymes by thyrotropin-releasing hormone in GH4C1 cells. AB - GH4C1 cells, which express Ca(2+)-dependent alpha- and beta- as well as Ca(2+) independent gamma-, epsilon- and zeta-protein kinase C (PKC) isozymes, provide a cell culture model for studying isozyme-specific properties and functions. Hormonal activation of PKCs regulates the differentiated functions of these cells, namely secretion and synthesis of prolactin (PRL). We previously reported that thyrotropin-releasing hormone (TRH) selectively down-modulates epsilon-PKC with no effect on alpha- or beta-PKCs (Kiley, S.C., Schaap, D., Parker, P., Hsieh, L.-L., and Jaken, S. (1990) J. Biol. Chem. 265, 15704-15712). We now extend those studies to explore the relationship between TRH-stimulated diacylglycerol (DAG) levels and epsilon-PKC down-modulation. TRH stimulates three distinct DAG phases in GH cells. Phase 1 DAG peaks at 15 s, is accompanied by a 6 fold increase in intracellular Ca2+, and causes the redistribution of alpha-, beta-, delta, and epsilon-PKC isozymes from a soluble to a detergent-insoluble particulate compartment. Phase 2 DAG peaks at 10 min, is not associated with a Ca2+ signal, and does not activate PKC by any criteria tested. Phase 3 DAG peaks at 6 h and is sustained through 12 h. This novel DAG phase is not associated with increased intracellular Ca2+. The time course of phase 3 DAG formation corresponds to the time course of TRH-stimulated epsilon-PKC down-regulation; maximal effects are observed at 6-12 h for both events. Unlike alpha-, beta-, and delta-PKCs which are preferentially distributed in the soluble fraction of resting GH cells, epsilon-PKC is also distributed in the detergent-insoluble particulate fraction. The selective compartmentalization of epsilon-PKC in the particulate fraction may render this pool uniquely susceptible to proteolytic degradation. The time course of phase 3 DAG formation and epsilon-PKC down modulation corresponds to the time course of decreasing PRL message synthesis in GH4 cells. The data suggests that loss of epsilon-PKC may be associated with the down-regulation of prolactin synthesis and that regulation of PRL gene transcription may be an epsilon-PKC-specific function in GH cells. PMID- 1748653 TI - Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. AB - Fluorescence measurements were used to monitor the interaction of the neurotoxin pardaxin and its analogues with membranes. Eight peptides were selectively labeled with the fluorophore 7-nitrobenz-2-oxa-1,3-diazole-4-yl, either at their N-terminal or at their C-terminal. No detectable changes in membrane permeability or hemolytic activity were observed upon modification. Upon the titration of solutions containing the different peptides with small unilamellar vesicles, the fluorescent emission spectra of 7-nitrobenz-2-oxa-1,3-diazole-4-yl-labeled pardaxin and its analogues, but not those of control peptides, displayed blue shifts in addition to enhanced intensities upon relocation of the probe to a more apolar environment. The results revealed that the N terminus of pardaxin is buried within the lipid bilayer while the C terminus is located at the bilayer's surface. Binding isotherms were obtained from the observed increases in the fluorescence emission yields, from which surface partition constants, in the range of 10(4) M-1, were in turn derived. The existence of an aggregation process was suggested by the shape of the binding isotherms. Furthermore, the results show good correlation between the incidence of aggregation and the ability of the different analogues to induce the release of relatively large molecules from vesicles. As such, our results suggest that the mechanism of pore formation employed by pardaxin and its analogues could be described by the "barrel stave" model. PMID- 1748654 TI - Function of glycoprotein Ib alpha in platelet activation induced by alpha thrombin. AB - We have obtained evidence that selective inhibition of high affinity thrombin binding sites located in the amino-terminal domain of the membrane glycoprotein (GP) Ib alpha results in impaired platelet activation, as shown by abrogation or reduction of the following responses induced in normal platelets by exposure to less than 1 nM alpha-thrombin: (i) increase in intracellular ionized calcium concentration ([Ca2+]i), (ii) release of dense granule content, (iii) binding of fibrinogen, (iv) aggregation. An anti-GP Ib monoclonal antibody, LJ-Ib 10, which does not inhibit von Willebrand factor binding to platelets, obliterated the high affinity alpha-thrombin-binding sites on normal platelets. Isotherms of alpha thrombin binding to normal platelets treated with saturating amounts of the antibody were virtually identical to those obtained with platelets from a patient with classical Bernard-Soulier syndrome. In parallel with decreased binding of the agonist, this antibody caused 50% inhibition of the maximal extent of platelet aggregation and 90% inhibition of ATP release induced by 0.3 nM alpha thrombin. By inhibiting alpha-thrombin binding to GP Ib, the antibody prevented the activation of platelets exposed to low concentrations of the agonist, as demonstrated by abrogation of the increase in intraplatelet ionized calcium concentration induced in control platelets by 0.18 nM alpha-thrombin; under these conditions, fibrinogen binding was inhibited by 84%. Therefore, there is a correlation between occupancy of the high affinity sites for alpha-thrombin on GP Ib alpha and platelet activation, secretion, and aggregation, suggesting that GP Ib alpha is part of an alpha-thrombin receptor relevant for platelet function. PMID- 1748655 TI - The carboxyl terminus of the S1 subunit of pertussis toxin confers high affinity binding to transducin. AB - The kinetic constants for the ADP-ribosylation of transducin were determined for the recombinant S1 subunit of pertussis toxin (rS1, composed of 235 amino acids) and two genetically derived deletion peptides, C180 and C195, which are composed of the 180 and 195 amino-terminal residues of the S1 subunit, respectively. Titration of NAD in the presence of a constant concentration of transducin (0.5 microM) showed that the KmappNAD in the ADP-ribosylation of transducin were similar, approximately 20 microM, for rS1, C195, and C180. In contrast, titration of transducin in the presence of a constant concentration of NAD (25 nM) showed that rS1 possessed a lower Kmapp(transducin) and greater kcat than either C195 or C180. Previous studies (Cortina, G., and Barbieri, J.T. (1991) J. Biol. Chem. 266, 3022-3030) showed that the 16 carboxyl terminal residues of the S1 subunit did not function in the ADP-ribosylation of transducin. It thus appears that residues between 195 and 219 of the S1 subunit are required for high affinity transducin binding and may be involved in the transfer of ADP-ribose to transducin. To localize the defect in the recognition of transducin by C180, rS1 and C180 were assayed for the ability to ADP-ribosylate either transducin or the purified alpha subunit of transducin (T alpha). Upon saturation of the target protein, rS1 ADP-ribosylated equivalent moles of transducin or T alpha, with the linear velocity of rS1-mediated ADP-ribosylation of transducin approximately 16 fold more rapid than the rate of ADP-ribosylation of T alpha. In contrast, the initial linear velocity of C180-mediated ADP-ribosylation of transducin was only 1.7-fold more rapid than the rate of ADP-ribosylation of T alpha. These data indicate that the amino-terminal 180 amino acids of S1 confer the specificity for ADP-ribosylation primarily through the interaction with T alpha, while residues between 195 and 219 of S1 confer high affinity binding to transducin primarily through the interaction, either directly or indirectly, with T beta gamma. PMID- 1748656 TI - The primary structure of the subunits of carbon monoxide dehydrogenase/acetyl-CoA synthase from Clostridium thermoaceticum. AB - CO dehydrogenase/acetyl-coenzyme A synthase (CODH) is the central enzyme in the pathway of acetyl-coenzyme A biosynthesis in Clostridium thermoaceticum. It catalyzes the interconversion of CO and CO2 and the synthesis of acetyl-coenzyme A from the methylated corrinoid/iron sulfur protein, CO, and coenzyme A. It is a nickel-iron-sulfur protein and contains two subunits in the form (alpha beta)3. Reported here is the cloning and sequencing of the genes for both subunits of CODH. The gene for the alpha subunit codes for a protein with 729 amino acids and a molecular weight of 81,730, and the beta gene for a protein with 674 amino acids and a molecular weight of 72,928. The alpha subunit follows the beta subunit by 23 bases and the genes for both subunits are preceded by a sequence which is similar to the Shine-Dalgarno sequence of Escherichia coli. No significant amino acid sequence homology has been found to any known sequence. Labeling CODH with 2,4-dinitrophenylsulfenyl chloride and isolating labeled peptide fragments demonstrated that a tryptophan, residue 418 of the alpha subunit, is protected by coenzyme A and thus may be considered a potential part of the coenzyme A site. PMID- 1748657 TI - Molecular characterization of the iron transport system mediated by the pJM1 plasmid in Vibrio anguillarum 775. AB - Complementation of insertion mutants showed that the polypeptides FatD, FatC, FatB, and FatA are essential for the iron-transport process encoded by pJM1. Sequence analysis followed by homology studies indicated that transport of ferric anguibactin into Vibrio anguillarum 775 follows the same mechanism as reported for transport of Fe(3+)-hydroxamates, Fe(3+)-catecholates, ferric dicitrate, and vitamin B12 into Escherichia coli. Homology of FatA, part of the receptor complex, to seven E. coli receptor proteins involved in uptake of siderophores and vitamin B12 supports the idea of a common ancestral gene. A "TonB-Box" was found in FatA suggesting the existence of a TonB-like protein function in V. anguillarum. A high homology in the primary structure of FatB to FhuD, FecB, FepB, and BtuE suggests that FatB is the anguibactin-binding protein located in the periplasmic space. FatD and FatC are polytopic integral membrane proteins. According to their homologies to other proteins from other transport systems, they may be involved in the translocation of ferric anguibactin across the cytoplasmic membrane. PMID- 1748658 TI - Biosynthesis of 5-hydroxybenzimidazolylcobamid (factor III) in Methanobacterium thermoautotrophicum. AB - Cultures of Methanobacterium thermoautotrophicum were supplemented with 13C labeled acetate or pyruvate, and the labeling pattern of the corrinoid, factor III, was established by 13C NMR spectroscopy. Complete 13C signal assignments were obtained by two-dimensional NMR experiments. The labeling pattern of factor III was analyzed by comparison with those of amino acids and nucleosides. The corrin ring system is derived from eight molecules of glutamate. The aminopropanol moiety is derived in a hitherto unknown pathway from pyruvate by reductive amination. The heterocyclic ring of hydroxybenzimidazole shares the labeling pattern of the imidazole ring of purines. The remaining four carbon atoms of the carbocyclic ring show the labeling signature of a carbohydrate with two of the carbons introduced from acetate and two from C-1 of pyruvate. However, erythrose can be ruled out as the specific precursor on the basis of a detailed investigation of aromatic amino acids indicating that erythrose 4-phosphate is obtained by reductive carboxylation of a triose precursor and not by the pentose phosphate cycle. PMID- 1748659 TI - Selective transcription of rat proenkephalin fusion genes from the spermatogenic cell-specific promoter in testis of transgenic mice. AB - The rat and mouse proenkephalin genes each contains two distinct promoters, one of which is utilized exclusively by spermatogenic cells. The germ cell-specific promoter lacks TATA sequences, is G+C rich, and contains multiple initiation sites. To investigate the nature of the cis-acting elements that determine selective transcription of the proenkephalin gene in male germ cells, two rat proenkephalin-chloramphenicol acetyltransferase fusion genes containing the two different promoter regions as well as 1.6 or 0.3 kilobases, respectively, of 5' flanking sequence were expressed in transgenic mice. Multiple transgenic lines were developed which expressed the fusion genes in testis, brain, and heart but not in tissues that do not normally express the proenkephalin gene. Fusion gene transcripts in transgenic mouse testes were localized to those spermatogenic cell types that utilize the spermatogenic cell promoter and were selectively and accurately initiated from the multiple rat germ cell start sites. Transgenic mice thus provide a useful model for the localization and characterization of cis acting elements mediating transcription of the proenkephalin gene from its germ cell-specific promoter. PMID- 1748660 TI - Crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella typhimurium at 2.7-A resolution. AB - A wide variety of sugars, amino acids, peptides, and inorganic ions are transported into bacteria by periplasmic transport systems consisting of substrate-specific receptors (binding proteins) and membrane-bound protein complexes. The crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) at 2.7-A resolution shows that the molecule has a bi-lobal structure and that its topological structure is different from other amino acid binding proteins but is similar to the sulfate-binding protein and maltose binding protein. High sequence homology between LAO and the histidine-binding protein (HisJ) and the fact that LAO and HisJ share the same membrane-bound protein complex allow one to define functional regions responsible for the ligand binding and for the interaction with the membrane complex. PMID- 1748661 TI - The K258R mutant of aspartate aminotransferase stabilizes the quinonoid intermediate. AB - Lys-258 of aspartate aminotransferase forms a Schiff base with pyridoxal phosphate and is responsible for catalysis of the 1,3-prototropic shift central to the transamination reaction sequence. Substitution of arginine for Lys-258 stabilizes the otherwise elusive quinonoid intermediate, as assessed by the long wavelength absorption bands observed in the reactions of this mutant with several amino acid substrates. The external aldimine intermediate is not detectable during reactions of this mutant with amino acids, although the inhibitor alpha methylaspartate does slowly and stably form this species. These results suggest that external aldimine formation is one of the rate-determining steps of the reaction. The pyridoxamine-5'-phosphate-like enzyme form (330-nm absorption maximum) is unreactive toward keto acid substrates, and the coenzyme bound to this species is not dissociable from the protein. PMID- 1748662 TI - Epimerization of 3-hydroxy-4-trans-decenoyl coenzyme A by a dehydration/hydration mechanism catalyzed by the multienzyme complex of fatty acid oxidation from Escherichia coli. AB - The mechanism of 3-hydroxyacyl-CoA epimerase (EC 5.1.2.3), which is associated with the multienzyme complex of fatty acid oxidation from Escherichia coli, was studied with D-3-hydroxy-4-trans-decenoyl-CoA as a substrate. The E. coli complex catalyzes the rapid and direct dehydration of D-3-hydroxy-4-trans-decenoyl-CoA to 2-trans,4-trans-decadienoyl-CoA, which is slowly hydrated to L-3-hydroxy-4-trans decenoyl-CoA. A kinetic analysis of the epimerase and its partial reactions established that epimerization of 3-hydroxyacyl-CoAs occurs solely by a dehydration/hydration mechanism. The results of a substrate competition study with L-3-hydroxy-4-trans-decenoyl-CoA and its D-isomer, together with the conclusion from a sequence analysis of the large subunit of the E. coli complex (Yang, X.-Y., Schulz, H., Elzinga, M., and Yang, S.-Y. (1991) Biochemistry 30, 6788-6795), prompt the suggestion that a single active site is responsible for the dehydration of the D- and L-isomers of 3-hydroxyacyl-CoAs. PMID- 1748663 TI - Purification and properties of a unique flavin-containing chloroperoxidase from the capitellid polychaete Notomastus lobatus. AB - A unique flavin-containing chloroperoxidase from the marine worm Notomastus lobatus was purified to homogeneity. This enzyme is composed of two dissociable protein moieties, a flavoprotein and a heme protein, in 1:1 molar ratio. The flavoprotein (Mr = 120,000) consists of four identical subunits having Mr of 30,000, and contains FAD. The heme protein (Mr = 54,000) is composed of two copies each of two non-identical subunits (Mr = 15, 500 and 11, 500) and contains ferriheme. The native N. lobatus chloroperoxidase (Mr = 174,000) therefore has a structure of alpha 4 beta 2 gamma 2. Neither the flavoprotein nor the heme protein alone has detectable chloroperoxidase activity but readily associate to form fully active enzyme. This enzyme is capable of oxidizing Cl-, Br-, and I- with optimum pH values of 4.5, 5.0, and 4.5, respectively, at 440 microM H2O2 and has halide-independent catalase activity in the absence of organic substrate. The enzyme can halogenate a wide variety of aromatic compounds, including phenol, from which it produces 4-bromophenol, 2,4-dibromophenol, and 2,4,6 tribromophenol. The same compounds are found in N. lobatus. The N. lobatus chloroperoxidase is the first haloperoxidase to be purified to homogeneity from a marine polychaete, the first reported to contain flavin, and has several unusual physical and catalytic properties. This chloroperoxidase appears to represent a new class of haloperoxidases. PMID- 1748664 TI - Mapping of trypsin cleavage and antibody-binding sites and delineation of a dispensable domain in the beta subunit of Escherichia coli RNA polymerase. AB - We have mapped principal sites in the Escherichia coli RNA polymerase molecule that are exposed to attack by trypsin under limited proteolysis conditions. The 1342-amino acid-long beta subunit is alternatively cleaved at Arg903 or Lys909. The cleavage occurs adjacent to a dispensable domain (residues 940-1040) that is absent in the homologous RNA polymerase subunits from chloroplasts, eukaryotes, and archaebacteria. In E. coli, this region can be disrupted with genetic deletions and insertions without the loss of RNA polymerase function. Insertion of 127 amino acids into this region introduces a new highly labile site for trypsin proteolysis. The dispensable domain carries the epitope for monoclonal antibody PYN-6 (near residue 1000), which can be used for anchoring the catalytically active enzyme on a solid support. We also report the identification of a secondary trypsin cleavage at Arg81 of the beta' subunit within a putative zinc-binding domain that is conserved in prokaryotes and chloroplasts. PMID- 1748665 TI - Mapping of the priming substrate contacts in the active center of Escherichia coli RNA polymerase. AB - The active center of DNA-dependent RNA polymerase performs the principal biochemical reaction of gene expression. Using cross-linkable substrate analogs and site-directed mutations, two evolutionarily invariant amino acids in the beta subunit of the Escherichia coli enzyme (Lys1065 and His1237) were mapped close to the binding site of the priming substrate of the reaction. Surprisingly, the mutational substitution of these residues (Lys1065----Arg and His1237----Ala) did not inactivate the catalytic function, but inhibited transition from the initiation to the elongation stage of transcription. PMID- 1748666 TI - Molecular characterization of a mammalian smooth muscle myosin light chain kinase. AB - A 5.6-kilobase cDNA clone has been isolated which includes the entire coding region for the myosin light chain kinase from rabbit uterine tissue. This cDNA, expressed in COS cells, encodes a Ca2+/calmodulin-dependent protein kinase with catalytic properties similar to other purified smooth muscle myosin light chain kinases. A module (TLKPVGNIKPAE), repeated sequentially 15 times, has been identified near the N terminus of this smooth muscle kinase. It is not present in chicken gizzard or rabbit skeletal muscle myosin light chain kinases. This repeat module and a subrepeat (K P A/V) are similar in amino acid content to repeated motifs present in other proteins, some of which have been shown to associate with chromatin structures. Immunoblot analysis after sodium dodecyl sulfate polyacrylamide gel electrophoresis, used to compare myosin light chain kinase present in rabbit, bovine, and chicken smooth and nonmuscle tissues, showed that within each species both tissue types have myosin light chain kinases with indistinguishable molecular masses. These data suggest that myosin light chain kinases present in smooth and nonmuscle tissues are the same protein. PMID- 1748668 TI - Purification, characterization, cloning, and amino acid sequence of the bifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase/5,10 methenyltetrahydrofolate cyclohydrolase from Escherichia coli. AB - We have purified the enzyme 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) from Escherichia coli to homogeneity by a newly devised procedure. The enzyme has been purified at least 2,000-fold in a 31% yield. The specific activity of the enzyme obtained is 7.4 times greater than any previous preparation from this source. The purified enzyme is specific for NADP. The protein also contains 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and behavior on a molecular sieving column suggest that the enzyme is a dimer of identical subunits. We have cloned the E. coli gene coding for the enzyme through the use of polymerase chain reaction based on primers designed from the NH2 terminal analysis of the isolated enzyme. We sequenced the gene. The derived amino acid sequence of the enzyme contains 287 amino acids of Mr 31,000. The sequence shows 50% identity to two bifunctional mitochondrial enzymes specific for NAD, and 40 45% identity to the presumed dehydrogenase/cyclohydrolase domains of the trifunctional C1-tetrahydrofolate synthase of yeast mitochondria and cytoplasm and human and rat cytoplasm. An identical sequence of 14 amino acids with no gaps is present in all 7 sequences. PMID- 1748667 TI - The carboxyl terminus of the smooth muscle myosin light chain kinase is expressed as an independent protein, telokin. AB - It has been proposed that the carboxyl terminus of the smooth muscle myosin light chain kinase is expressed as an independent protein. This protein has been purified from tissues and named telokin (Ito, M., Dabrowska, R., Guerriero, V., Jr., and Hartshorne, D. J. (1989) J. Biol. Chem. 264, 13971-13974). In this study we have isolated and characterized cDNA and genomic clones encoding telokin. Analysis of a genomic DNA clone suggests that the mRNA encoding telokin arises from a promoter which appears to be located within an intron of the smooth muscle myosin light chain kinase (MLCK) gene. This intron interrupts exons encoding the calmodulin binding domain of the kinase. The amino acid sequence deduced from the cDNA predicts that telokin is identical to the carboxyl-terminal 155 residues of the smooth muscle MLCK. Unlike the smooth muscle MLCK which is expressed in both smooth and non-muscle tissues, telokin is expressed in some smooth muscle tissues but has not been detected in aortic smooth muscle or in any non-muscle tissues. PMID- 1748669 TI - Presence of terminal N-acetylgalactosamine residues in subregions of the endoplasmic reticulum is influenced by cell differentiation in culture. AB - Using Helix pomatia lectin as a specific probe for terminal, nonreducing N acetylgalactosamine residues, glycoprotein precursors bearing newly initiated O linked oligosaccharides have been localized in the lumen of the endoplasmic reticulum and cis-Golgi cisternae. This pattern contrasts with the detection of the terminal disaccharide galactose beta-1,3-N-acetylgalactosamine by Arachis hypogaea lectin in middle and trans-Golgi compartments, which are considered elongation sites for O-glycosylation. Distribution of H. pomatia ligands in the endoplasmic reticulum is confined to specialized regions or subcompartments in both human colonic adenocarcinoma cells and cultured chicken chondrocytes. Since in cartilage, chondrocytes contain H. pomatia-binding sites exclusively concentrated in cis-Golgi cisternae, primary cultures of this cell type have been used to study those conditions that promote initiation of O-glycosylation in the endoplasmic reticulum. A correlation has been found between the age of the culture and the extent of reactivity of the endoplasmic reticulum with either H. pomatia lectin or antibody against the sequence GalNAc alpha-serine/threonine (Tn antigen). Cells showing an extensive reaction are not hindered in their secretory activity and still maintain the chondrocyte phenotype. Taken together the results suggest that the intracellular distribution of the glycosylation enzymes is not only cell type-specific as previously shown (Roth, J., Taatjes, D. J., Weinstein, J., Paulson, J. C., Greenwell, P., and Watkins, W. M. (1986) J. Biol. Chem. 261, 14307-14312) but it might also vary depending on the stage of cell differentiation. PMID- 1748670 TI - The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. AB - Site-directed mutagenesis was used to study the cysteine residue involved in the assembly of human acetylcholinesterase (HuAChE) catalytic subunits. Substitution of the cysteine at position 580 by alanine resulted in impairment of interchain disulfide bridge formation; the mutagenized enzyme (C580A) was secreted from recombinant cells in the monomeric form and failed to assemble into dimers. The mutant monomeric HuAChE did not differ from the native oligomeric enzyme neither in rate of catalysis nor in affinity to acetylthiocholine. Mutant monomers were also shown to retain the acetylcholinesterase characteristic sensitivity to high substrate concentrations. The mutation did not seem to affect the efficiencies of either synthesis or secretion of recombinant HuAChE polypeptides, as was demonstrated in cell lines derived from human embryonic kidney (293 cells) as well as from a human neuroblastoma (SK-N-SH). Furthermore, the mutation did not lead to an increase in accumulation of intracellular HuAChE polypeptides, suggesting that export of acetylcholinesterase from cells may not be coupled to subunit assembly. PMID- 1748671 TI - The type I and type II bovine scavenger receptors expressed in Chinese hamster ovary cells are trimeric proteins with collagenous triple helical domains comprising noncovalently associated monomers and Cys83-disulfide-linked dimers. AB - Scavenger receptors have been implicated in the development of atherosclerosis and other macrophage-associated functions. The structures and processing of type I and type II bovine macrophage scavenger receptors were examined using polyclonal anti-receptor antibodies. Pulse/chase metabolic labeling experiments showed that both types of scavenger receptors expressed in Chinese hamster ovary (CHO) cells behaved as typical cell surface membrane glycoproteins. They were synthesized as endoglycosidase H-sensitive precursors which were converted to endoglycosidase H-resistant mature forms expressed on the cell surface. The reduced precursor and mature forms were doublets on sodium dodecyl sulfate-gel electrophoresis, primarily because of heterogeneous N-glycosylation. The approximate molecular sizes were: type I precursor, 65/63 kDa; type I mature, 82/76 kDa; type II precursor, 57/53 kDa; and type II mature, 72/65 kDa. During post-translational processing, the cysteine-rich C terminus (SRCR domain) of some of the type I receptors was proteolytically removed to form a relatively stable, approximately 69-kDa degradation product. Type II receptors differ from type I receptors in that they do not have SRCR domains and an analogous proteolytic cleavage was not observed. Several experiments provided strong evidence that the Gly-X-Y-repeat domains in the scavenger receptors oligomerize into collagenous triple helices. For example, alpha,alpha'-dipyridyl, an inhibitor of the collagen modifying enzymes prolyl and lysyl hydroxylases, interfered with both the kinetics and nature of post-translational receptor processing, and both precursor and mature forms of the receptors in intact cells could be cross-linked with difluorodinitrobenzene into reduction-resistant trimers. In intact cells, precursor receptor trimers (type I, 198 kDa; type II, 176 kDa) were assembled in the endoplasmic reticulum by the noncovalent association of monomers and Cys83 disulfide-linked dimers (type I, 129 kDa; type II, 119 kDa). When cells were lysed in the absence of the sulfhydryl trapping agent iodoacetamide, oxidation of the side chain of Cys17 in the cytoplasmic domain leads to the artifactual formation of reduction-sensitive covalently linked trimers. The approximate masses of the mature dimer and trimer forms were 162 and 237 kDa for type I receptors and 147 and 219 kDa for type II receptors. Cys83-disulfide-linked dimer formation was not required for function because mutant receptors (Cys83----Gly83) assembled into trimers of noncovalently associated monomers and exhibited normal receptor activity. Treatment of cells with difluorodinitrobenzene cross-linked some of the receptors into complexes larger than trimers, raising the possibility that the trimers may assemble into higher order oligomers. PMID- 1748672 TI - Site-specific DNA cleavage by antisense oligonucleotides covalently linked to phenazine di-N-oxide. AB - Site-specific degradation of DNA was achieved by the use of DNA oligonucleotides covalently tethered to phenazine 5,10-di-N-oxide. When annealed to a complementary DNA target strand, the antisense oligonucleotide effected alkylation of guanosine residues in proximity to the phenazine di-N-oxide prosthetic group. Admixture of dithiothreitol to the formed duplex resulted in reductive activation of the phenazine di-N-oxide moiety with concomitant generation of diffusible oxygen radicals; the latter effected strand scission of the target DNA oligonucleotide. Several parameters of DNA degradation were studied, including the effect on DNA degradation of chain length in the tether connecting the oligonucleotides and prosthetic group, the relative efficiencies of DNA cleavage when the prosthetic group was in the middle or at the end of the antisense oligonucleotide, and the effect of O2 on DNA degradation. Also studied was the actual chemistry of DNA oligonucleotide degradation and the ability of individual diastereomers of the modified oligonucleotides to mediate degradation of the target DNA. PMID- 1748673 TI - Site-directed mutagenesis and expression of PC2 in microinjected Xenopus oocytes. AB - The biosynthesis and post-translational maturation of PC2, a neuroendocrine specific Kex2-like endoprotease, following expression in Xenopus oocytes is described. The initial translation product was a 75-kDa membrane-associated protein which was released from the oocytes as a glycosylated 71-kDa protein. During extended chase periods, the extracellular 71-kDa protein was converted to a mature 68-kDa product. A deletion mutant lacking a putative COOH-terminal amphipathic helix was still membrane-associated, suggesting that this domain was not essential for attachment of PC2 to membranes. Two putative proregion cleavage site mutants were also constructed. Conversion of the 75-kDa peptide to the 71 kDa peptide involved cleavage at the sequence Lys-Arg-Arg-Arg (amino acids 78 81), since mutation of this sequence to Lys-Val-Arg-Leu resulted in the secretion of the 75-kDa peptide. Extracellular conversion of the 71-kDa peptide to the 68 kDa peptide involved cleavage at the sequence Arg-Lys-Lys-Arg (amino acids 106 109), since deletion of this tetrabasic sequence resulted in secretion of the 71 kDa peptide without further conversion to the 68-kDa form. Finally, a mutation which changed a catalytically important Asp to Asn did not affect processing of proPC2. These results may be relevant to our understanding of mechanisms in the intracellular sorting and maturation of proPC2 in neuroendocrine cells. PMID- 1748674 TI - Use of radiation suicide to isolate constitutive and temperature-sensitive conditional Chinese hamster ovary cell mutants with defects in the endocytosis of low density lipoprotein. AB - A radiation suicide procedure was used to isolate cells with either constitutive or temperature-sensitive (ts) defects in the receptor-mediated endocytosis of low density lipoprotein (LDL). Mutagen-treated Chinese hamster ovary cells maintained at 34 degrees C (permissive temperature) were shifted to 39.5 degrees C (nonpermissive temperature) for 14-26 h and incubated at 39.5 degrees C for an additional 6-8 h with [3H]cholesteryl linoleate LDL. Wild-type cells internalized this lipoprotein via LDL receptors and accumulated [3H]cholesteryl linoleate (1.5 2 dpm/cell). Radiolysis during 80 days of frozen storage killed most of these cells (radiation suicide). Receptor-deficient cells were identified by screening the surviving cells for their inability to internalize and accumulate 125I-LDL using a replica plating assay. From 3.6 x 10(7) tritium-labeled cells, two clones fell into previously defined constitutive and ts complementation groups (ldlA and ldlG, respectively). Another constitutive and two other ts mutants defined two new complementation groups, ldlI (constitutive) and ldlH (ts). This increases to nine the current number of recessive, LDL receptor-deficient, Chinese hamster ovary complementation groups. All of the mutants with ts defects in LDL endocytosis exhibited ts conditional-lethal phenotypes. At the nonpermissive temperature, the rates of loss of LDL receptor activity (t 1/2 = 10-14 h) were significantly faster than the rates of loss of protein synthesis (t 1/2 greater than 24 h), suggesting that the temperature sensitivity of receptor activity was not simply due to the metabolic collapse of dying cells. Detailed analysis of these new classes of mutants should help define gene products and functions required for LDL receptor activity. PMID- 1748675 TI - Expression of human aldose and aldehyde reductases. Site-directed mutagenesis of a critical lysine 262. AB - Human aldose reductase (EC 1.1.1.21) and aldehyde reductase (EC 1.1.1.2) are implicated in the development of diabetic complications by a variety of mechanisms, and a number of drugs to inhibit these enzymes have been proposed for the therapy and prevention of these complications. To probe the structure and function of these two enzymes, we used site-directed mutagenesis in the cDNAs of both enzymes to replace lysine 262 with methionine. Wild-type and mutant enzymes were overexpressed in Escherichia coli and purified by anion exchange and affinity chromatography. N-terminal sequence analysis, Western blots, and kinetic studies confirmed the identity of the recombinant wild-type enzymes with the native human placental and liver enzymes. Recombinant aldose reductase (hAR) and aldehyde reductase (hGR) have apparent kinetic constants virtually identical to their respective native enzymes. The mutant aldose reductase (hARK262 greater than M) shows a 66-fold increase in Km for NADPH with respect to the wild type (1.9 +/- 0.4 microM versus 125 +/- 14 microM), whereas the Km for DL glyceraldehyde increased 35-fold (20 +/- 2 versus 693 +/- 41 microM). The same constants for the mutant aldehyde reductase (hGRK262 greater than M) increased 97 and 86-fold, respectively (from 2.0 +/- 0.4 to 194 +/- 16 microM and from 1.6 +/ 0.4 to 137 +/- 3 mM). These results indicate that lysine 262 in aldose reductase and aldehyde reductase is crucial to their catalytic activity by affecting co factor binding. PMID- 1748676 TI - Localization of UDP-GalNAc:NeuAc alpha 2,3Gal-R beta 1,4(GalNAc to Gal)N acetylgalactosaminyltransferase in human stomach. Enzymatic synthesis of a fundic gland-specific ganglioside and GM2. AB - A glycolipid detected in human gastric mucosa with anti-GM2 monoclonal antibody was characterized to be GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4GlcNAc beta 1 3Gal 1-4Glc-Cer (NGM-1), which was lost in gastric cancer tissue with complementary increase of GM2 sharing the same terminal carbohydrate structure as NGM-1 (Dohi, T., Ohta, S., Hanai, N., Yamaguchi, K., and Oshima, M. (1990) J. Biol. Chem. 265, 7880-7885). The study on differential expression of NGM-1 in gastric fundic mucosa, pyloric mucosa, gastric cancer, and various other tissues indicated that NGM-1 existed specifically in fundic mucosa. The content of GM3 and sialylparagloboside (SPG), which are the substrates for the synthesis of GM2 and NGM-1, respectively, were not significantly different in these tissues. Therefore, the presence of two kinds of beta 1,4GalNAc transferases having different substrate specificity was considered to be critical for the expression of NGM-1 and GM2. The activity of beta 1,4GalNAc transferase which synthesizes GM2 or NGM-1 was determined by detecting the products with specific monoclonal antibodies. The activity of beta 1,4GalNAc transfer to SPG was high in fundic mucosa, while it was absent in pyloric mucosa or cancer. On the other hand, the increased activity of beta 1,4GalNAc transfer to GM3 was observed in cancer tissues and cancer cell lines which were rich in GM2. Our conclusion is that the limited expression of NGM-1 in fundic mucosa and the increase of GM2 in cancer are attributed to two types of beta 1,4GalNAc transferases localized in each region with different substrate specificity; the one in fundic mucosa transfers GalNAc to SPG but not to GM3, and the other one enhanced in cancer transfers GalNAc to GM3 but not to SPG. PMID- 1748677 TI - Glucose increases the expression of the ATP/ADP translocator and the glyceraldehyde-3-phosphate dehydrogenase genes in Chlorella. AB - A presumably full-length cDNA clone of the mitochondrial ATP/ADP translocator (AAT) of Chlorella kessleri has been isolated and sequenced. The expression of the AAT gene is highly increased in the presence of D-glucose (14 mM). At least nine more genes are activated when autotrophically grown Chlorella cells switch to heterotrophic growth. Among these is the HUP1 gene coding for the hexose transporter (Sauer, N., Caspari, T., Klebl, F., and Tanner, W. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7949-7952) and, as also shown in this paper, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. When glucose or the nonmetabolizable analogue 6-deoxyglucose is added to the cells, an increased expression of GAPDH or AAT is observed after 10 or 30 min, respectively. Hexose uptake mutants (HUP1-) do not respond to sugars in this way, which indicates that either the inducer has to be internalized or that the HUP1 translocator is part of the signal transduction mechanism. PMID- 1748678 TI - Molecular basis of multiple UDP-glucuronosyltransferase isoenzyme deficiencies in the hyperbilirubinemic rat (Gunn rat). AB - The Gunn rat is a mutant strain of Wistar rat which has unconjugated hyperbilirubinemia as a result of the absence of hepatic UDP glucuronosyltransferase (UDPGT) activity toward bilirubin. The Gunn rat is also deficient in UDPGT activities toward phenol substrates, and also toward digitoxigenin-monodigitoxiside. We have demonstrated that the defect of the isoenzyme for 4-nitrophenol (4NP) in Gunn rat liver arises from a -1 frameshift mutation that removes 115 amino acids from the COOH terminus (Iyanagi, T., Watanabe, T., and Uchiyama, Y. (1989) J. Biol. Chem. 264, 21302-21307). To investigate the molecular basis of defects in other UDPGT isoenzymes, we isolated and sequenced cDNAs from a Gunn rat liver library using mutant 4NP-UDPGT cDNA as a probe. Three novel cDNAs were identified that had identical 3'-regions of 1362 base pairs containing a single-base deletion in the same position as that of the mutant 4NP-UDPGT cDNA. However, their 5'-regions, encoding the substrate-binding domain, showed no more than 40% homology to that of 4NP-UDPGT. These data provide evidence that defects in some UDPGT isoenzymes in the Gunn rat are caused by a single mutation that results in the formation of a common truncated COOH terminus. Furthermore, the data also suggest that these mRNAs are transcribed from a single gene and that the 5'-exons are transcribed independently and differentially spliced to common 3'-exons encoding the conserved domain. PMID- 1748679 TI - Genomic organization of collagenous domains and chromosomal assignment of human 180-kDa bullous pemphigoid antigen-2, a novel collagen of stratified squamous epithelium. AB - We have recently isolated a 1.0-kilobase (kb) cDNA encoding 180-kDa bullous pemphigoid antigen (BPAG2), an autoantigen in blistering skin disease, bullous pemphigoid (Giudice, G. J., Squiquera, H. L., Elias, P. M., and Diaz, L. (1991) J. Clin. Invest. 87, 734-738). The deduced amino acid sequence identified two collagenous domains characterized by Gly-X-Y repeats. In this study we have elucidated the genomic organization of the corresponding segment in the human BPAG2 gene. Screening of a genomic lambda-phage DNA library yielded six overlapping clones, and the sequences corresponding to the 1.0-kb cDNA spanned approximately 12 kb of genomic DNA. The coding segment consisted of 19 separate exons varying in size from 27 to 222 base pairs. The organization of these exons and the splice sites at the intron-exon junctions were clearly different from other fibrillar and nonfibrillar collagen genes described to date. The BPAG2 gene was mapped by chromosomal in situ hybridization to the long arm of human chromosome 10, at locus 10q24.3; this location is distinct from any previously mapped collagens, and it also distinguishes BPAG2 from BPAG1, a 230-kDa bullous pemphigoid antigen, which has been mapped to chromosome 6p (Sawamura, D., Nomura, K., Sugita, Y., Mattei, M.-G., Chu, M.-L., Knowlton, R.G., and Uitto, J. (1990) Genomics 8, 722-726). These data suggest that BPAG2 is a novel collagen present in stratified squamous epithelia. PMID- 1748680 TI - Purified estrogen receptor DNA binding domain expressed in Escherichia coli activates transcription of an estrogen-responsive promoter in cultured cells. AB - The region of the Xenopus laevis estrogen receptor responsible for interaction with DNA, the DNA binding domain (DBD), has been cloned and overexpressed in Escherichia coli using a T7 RNA polymerase expression system. Extracts from cells transformed with the DBD expression vector contain a single protein which reacts with polyclonal antibodies to estrogen receptor and exhibits sequence-specific binding to a DNA fragment containing a consensus estrogen response element. The DBD protein has been purified to near homogeneity. Determination of the rotational relaxation time of the dansylated DBD by fluorescence polarization and size fractionation by Superdex column chromatography indicate that the DBD is a monomer in solution. The DBD forms a single protein-estrogen response element complex in gel mobility shift assays at DBD concentrations of 18-3,600 nM, suggesting that the DBD is bound to both halves of the palindromic estrogen response element. To investigate the ability of the DBD expressed in bacteria to activate gene expression, we have developed a simple liposome-based system for delivery of protein into cultured cells. Transfected DBD protein elicited large, concentration-dependent increases in transcription of an estrogen receptor regulated reporter gene. These data demonstrate that the bacterially expressed DNA binding domain, which represents a small portion of the Xenopus laevis estrogen receptor, retains significant ability to activate transcription of an estrogen-responsive promoter in vertebrate cells. PMID- 1748681 TI - Two additional common subunits, ABC10 alpha and ABC10 beta, are shared by yeast RNA polymerases. AB - Yeast nuclear RNA polymerases are multisubunit enzymes that contain in common some small subunits. We show that the smallest, a 10-kDa component of three enzymes (A10, B10, and C10), is heterogeneous. In each case, it can be resolved into two distinct polypeptides (alpha and beta) by reverse-phase chromatography. A10 alpha, B10 alpha, and C10 alpha were indistinguishable on the basis of their electrophoretic and chromatographic behaviors, characteristic silver staining, and tryptic peptide analysis. All three polypeptides are blocked at their amino termini. By the same criteria, A10 beta, B10 beta, and C10 beta were also indistinguishable. The amino-terminal sequence of A10 beta and C10 beta corresponded to that of subunit B10 recently cloned by Woychik and Young (Woychik, N. A., and Young, R. A. (1990) J. Biol. Chem. 265, 17816-17819). Thus, the three forms of RNA polymerase share two additional and distinct polypeptides, ABC10 alpha and ABC10 beta, that therefore can be considered bona fide subunits of these enzymes. Interestingly, these two subunits bind zinc. PMID- 1748682 TI - Early induction of ribonucleotide reductase gene expression by transforming growth factor beta 1 in malignant H-ras transformed cell lines. AB - Previous investigations have indicated that the suppression of proliferation by transforming growth factor (TGF) beta 1 is often lost upon cellular transformation, and that proliferation of some tumors is stimulated by TGF-beta. The present study provides the first observation of a link between TGF-beta 1 regulation of this process and alterations in the expression of ribonucleotide reductase, a highly controlled rate-limiting step in DNA synthesis. A series of radiation and T24-H-ras-transformed mouse 10T1/2 cell lines exhibiting increasing malignant potential was evaluated for TGF-beta 1 induced alterations in ribonucleotide reductase M1 and M2 gene expression. Early increases in M1 and/or M2 message and protein levels were observed only in malignant cell lines. The TGF beta 1 induced changes in M1 and/or M2 gene expression occurred prior to any detectable changes in the rates of DNA synthesis, supporting the novel concept that ribonucleotide reductase gene expression can be elevated by TGF-beta 1 without altering the proportion of cells in S phase. T24-H-ras-transformed 10T1/2 cells were transfected with a plasmid containing the coding region of TGF-beta 1 under the control of a zinc-sensitive metallothionein promoter. When these cells were cultured in the presence of zinc, a large induction of TGF-beta 1 message was observed within 1 h. Both M1 and M2 genes were also induced, with increased mRNA levels appearing 2 h after zinc treatment, or 1 h after TGF-beta 1 message levels were clearly elevated. In total, the data suggests a mechanism of autocrine stimulation of malignant cells by TGF-beta 1, in which early alterations in the regulation of ribonucleotide reductase may play an important role. PMID- 1748683 TI - A site-directed approach for constructing temperature-sensitive ubiquitin conjugating enzymes reveals a cell cycle function and growth function for RAD6. AB - We have determined the gene sequence of a temperature-sensitive allele of the cell cycle-related ubiquitin-conjugating enzyme CDC34 (UBC 3) from Saccharomyces cerevisiae. The basis of temperature sensitivity is a missense mutation resulting in a proline to serine substitution at a residue that is conserved in all ubiquitin-conjugating enzymes identified thus far. This observation raised the possibility that other temperature-sensitive ubiquitin-conjugating enzymes could be generated in the same way. We therefore created the corresponding substitution in the DNA repair-related ubiquitin-conjugating enzyme, RAD6 (UBC2), and examined the effect of temperature on the cell proliferation and DNA repair-related functions of this altered polypeptide. Yeast strains carrying this mutation proved to be temperature-sensitive with respect to cell proliferation but not with respect to the DNA damage-processing phenotypes exhibited by other rad6 mutants. Upon further investigation of the proliferation defect exhibited by this mutant, we discovered that other rad6 gene mutants deleted for the gene undergo cell cycle arrest at the nonpermissive temperature, whereas the engineered temperature-sensitive allele showed no evidence of a cell cycle defect. From these findings, we conclude that the proliferation function of RAD6 can be subdivided into a growth component and a cell division cycle component and that the growth component is unrelated to the DNA repair functions of RAD6. A reasonable interpretation of these results is that different proteins are targeted for ubiquitination in each case. The conserved proline residue of RAD6 and CDC34 is part of a turn motif common to all ubiquitin-conjugating enzymes. It is therefore likely that site-directed substitution of prolines located in turns can be generally applied for the creation of other temperature-sensitive ubiquitin-conjugating enzymes and possibly other proteins as well. PMID- 1748684 TI - Erythropoietin induces cytosolic protein phosphorylation and dephosphorylation in erythroid cells. AB - Erythropoietin, the prime regulator of red blood cell growth and differentiation, causes rapid changes in the phosphorylation of several integral plasma membrane proteins (Choi, H-S., Wojchowski, D. M., and Sytkowski, A. J. (1987) J. Biol. Chem. 262, 2933-2936; Choi, H-S., Bailey, S. C., Donahue, K. A., Vanasse, G. J., and Sytkowski, A. J. (1990) J. Biol. Chem. 265, 4143-4148). In the present study we have demonstrated that erythropoietin's signal is transduced rapidly to the cytosol resulting in specific phosphorylation/dephosphorylation events. Erythropoietin treatment of Rauscher murine erythroleukemia cells previously labeled with [32P]orthophosphate results in a rapid increase in phosphorylation of two cytosolic proteins, designated pp96 and pp80, and a decrease in phosphorylation of another protein, designated pp90. The relative molecular mass and pI of pp80 are virtually identical to those reported for the protein kinase C substrate p80, or "MARCKS protein." Treatment of the cells with 12-O tetradecanoylphorbol-13-acetate also increases pp80 but not pp96 phosphorylation, suggesting that erythropoietin triggers a protein kinase C-dependent pathway to pp80 and a protein kinase C-independent pathway to pp96. The effect of erythropoietin on pp96 phosphorylation was also shown in nontransformed erythroid cells isolated from the spleens of phenylhydrazine-treated mice. In contrast, almost no 32P labeling of pp80 or pp90 was detected, and pp80 and pp90 protein were nearly absent from these normal cells. These differences in expression and phosphorylation of erythropoietin-sensitive phosphoproteins may be related to the growth factor independence or dependence of the erythroid cells. PMID- 1748685 TI - Protein kinase C (PKC) activation via human leucocyte antigen class II molecules. A novel regulation of PKC activity. AB - Analysis of intracellular localization of protein kinase C (PKC) in a lymphoblastoid B cell line shows that anti-human leucocyte antigen (HLA) class II antibodies induce an increase of cytosolic and membrane PKC activities. This phenomenon is both time- and dose-dependent. The maximal PKC activation was observed after exposure to 12.5 micrograms/ml antibody for 30 to 45 min. Unlike TPA, no translocation of the cytosolic PKC was observed at any time following exposure to the anti-HLA class II antibodies. We observed a good correlation between the [3H]phorbol dibutyrate binding activity and the enzymatic activity of PKC. Using a panel of antibodies specific for the HLA class II isotypes (DP, DQ, DR), we demonstrated that PKC activation via HLA class II molecules is not restricted to one isotype. We also showed by Western blot analysis that the increased PKC activity correlates with a quantitative increase of PKC. The increase of PKC activity induced by anti-HLA class II antibodies was completely abolished by the treatment with actinomycin D, a transcriptional inhibitor, or cycloheximide, a translational inhibitor. Finally, Northern blot analysis revealed that anti-HLA class II antibodies induce an increase of the PKC alpha and PKC beta mRNAs levels which are significant after 20 min of stimulation and rose to a maximum after 60 min. In summary, our results show that increased PKC activity induced by HLA class II antibody is regulated at the transcriptional level. PMID- 1748686 TI - Expression of human glycophorin A in wild type and glycosylation-deficient Chinese hamster ovary cells. Role of N- and O-linked glycosylation in cell surface expression. AB - Glycophorin A, the most abundant sialoglycoprotein on human red blood cells, carries several medically important blood group antigens. To study the role of glycosylation in surface expression and antigenicity of this highly glycosylated protein (1 N-linked and 15 O-linked oligosaccharides), glycophorin A cDNA (M allele) was expressed in Chinese hamster ovary (CHO) cells. Both wild type CHO cells and mutant CHO cells with well defined glycosylation defects were used. Glycophorin A was well expressed on the surface of transfected wild type CHO cells. On immunoblots, the CHO cells expressed monomer (approximately 38 kDa) and dimer forms of glycophorin A which co-migrated with human red blood cell glycophorin A. The transfected cells specifically expressed the M blood group antigen when tested with mouse monoclonal antibodies. Tunicamycin treatment of these CHO cells did not block surface expression of glycophorin A, indicating that, in the presence of normal O-linked glycosylation, the N-linked oligosaccharide is not required for surface expression. To study O-linked glycosylation, glycophorin A cDNA was transfected into the Lec 2, Lec 8, and ldlD glycosylation-deficient CHO cell lines. Glycophorin A with truncated O-linked oligosaccharides was well expressed on the surface of ldlD cells (cultured in the presence of N-acetylgalactosamine alone), Lec 2 cells, and Lec 8 cells with monomers of approximately 25 kDa, approximately 33 kDa, and approximately 25 kDa, respectively. In contrast, non-O-glycosylated glycophorin A (approximately 19-kDa monomers) was poorly expressed on the surface of ldlD cells cultured in the absence of both galactose and N-acetylgalactosamine. Thus, under these conditions, in the absence of O-linked glycosylation, the N-linked oligosaccharide itself is not able to support appropriate surface expression of glycophorin A in transfected CHO cells. PMID- 1748687 TI - A Chinese hamster cDNA encoding a protein essential for phosphatidylserine synthase I activity. AB - A phosphatidylserine-auxotrophic mutant of cultured Chinese hamster ovary (CHO) cells, PSA-3, is defective in phosphatidylserine synthase I activity. Transfection of PSA-3 cells with a cDNA expression library of CHO-K1 (the parent of PSA-3) yielded a phosphatidylserine-prototrophic transformant with normal phosphatidylserine synthase I activity. Using a cDNA segment retrieved from the transformant as a probe, a cDNA clone (pssA) responsible for phosphatidylserine prototrophy was isolated from the original cDNA library by colony filter hybridization. Introduction of the pssA cDNA into PSA-3 cells restored the phosphatidylserine content, and the resultant transformant exhibited 15-fold higher specific phosphatidylserine synthase I activity than CHO-K1 cells. The nucleotide sequence of the pssA cDNA contained a single long open reading frame capable of encoding a protein of 471 amino acid residues with several putative membrane-spanning domains. Our results indicated that the pssA cDNA encodes an integral membrane protein essential for phosphatidylserine synthase I activity. PMID- 1748688 TI - Identification and chemical synthesis of a substrate-binding site for factor IX on coagulation factor XIa. AB - We have previously used monoclonal antibodies to identify an epitope on the heavy chain of factor XIa that is a substrate-binding site for factor IX (Sinha, D., Seaman, F.S., and Walsh, P.N. (1987) Biochemistry 26, 3768-3775; Baglia, F.A., Sinha, D., and Walsh, P.N. (1989) Blood 74, 244-251). To define the factor XIa domain that binds factor IX, we have now screened a panel of factor XI heavy chain-derived synthetic peptides for their capacity to inhibit the formation of an activation peptide reflecting factor IX activation by factor XIa. Peptide Asn145-Ala176 (which is located in the second tandem repeat or A2 domain of the factor XI heavy chain) is a competitive inhibitor of factor IX activation by factor XIa with a Ki of 30 nM, whereas structurally similar peptides in the A1, A3, and A4 domains were required at 10-1000-fold higher concentrations for similar effects, and a synthetic peptide identical with a highly homologous region of the heavy chain A2 domain of prekallikrein (Tyr143-Ala176) had no effect on factor IX activation by factor XIa. Because detailed structural information is lacking, a potential three-dimensional structure for the factor XI A2 domain was calculated based on its sequence information in conjunction with previously determined structural constraints. The resulting structure depicted three juxtaposed beta-stranded stem-loops that, based on biological information, constitute a candidate surface for contact with factor IX. The A2 model was therefore used as a template in the rational design of three synthetic peptides (Ala134-Ile146 (peptide a), Leu148-Arg159 (peptide b), and Ile160-Leu172 (peptide c]. When peptides a and b or a and c were added together and the activation of factor IX by factor XIa was examined, a synergistic inhibitory effect was observed, compared with each peptide added individually, whereas peptides b and c showed additive effects. Our data suggest that the sequence of amino acids from Ala134 through Leu172 of the heavy chain of factor XI contains three antiparallel beta-strands connected by beta-turns that together comprise a continuous surface utilized for the binding of factor IX. PMID- 1748689 TI - Studies on the interaction of ribonuclease inhibitor with pancreatic ribonuclease involving differential labeling of cysteinyl residues. AB - Ribonuclease inhibitor (RI) is a protein that forms a very tight complex with ribonucleases (RNases) of the pancreatic type. RI contains 30 thiol groups, some of which are important for the enzyme-inhibitor interaction. To examine which thiols are affected by the binding of RNase, differential labeling experiments were performed. Reaction of porcine RI with the cysteine-specific labeling reagent 4-N,N-dimethylaminoazobenzene-4'-iodoacetamido-2'-sulfonic acid resulted in labeling of an average of 7.4 of the 30 cysteinyl residues. Binding of bovine pancreatic RNase A caused a 3.2-fold reduction in the extent of modification. Peptide mapping showed that in free RI, Cys-57, -371, and -404 were labeled to the greatest extent (yield, 0.4-0.6 mol/mol). RNase A did not protect Cys-57 against modification, whereas the labeling of Cys-371 and -404 was reduced by more than 90%. A second group of residues was labeled to a lesser extent in free RI (yield, 0.04-0.2 mol/mol). Within this group 11 residues were protected by RNase A by more than 90%, 2 were not affected at all, and 7 were protected between 10 and 90%. Seven cysteinyl residues in RI that were protected in the RI.RNase A complex were no longer protected in the RI.S-protein complex. These residues were mainly present in the N-terminal region of RI. However, when the S peptide was included to yield the RI.RNase S complex, the same pattern of labeling was obtained as with the RI.RNase A complex. Addition of the S-peptide alone had no effect on the labeling. The implications of these observations with respect to RNase binding areas of RI are discussed in relation to the results obtained from the analysis of active RI molecules that contain deletions. PMID- 1748690 TI - Characterization of the active part of the human transferrin gene enhancer and purification of two liver nuclear factors interacting with the TGTTTGC motif present in this region. AB - The human transferrin gene enhancer is composed of two functional domains (A and B). We have previously shown that domain A is able to mediate enhancer activity in transient expression experiments. Here, we show that multimers of the domain A single enhanson coupled to a canonical TATA box are sufficient to promote transcription in vitro with liver nuclear extracts. Gel mobility shift assays reveal the binding of two liver nuclear factors to this enhanson, and methylation interference experiments show that the motif 5'-TGTTTGCTTT-3' is the target site for these factors. This was confirmed by the use of mutants in gel retardation assays and transient expression experiments. The two proteins interacting with the decanucleotide have been purified from rat liver nuclear extracts by DNA affinity chromatography. The purified proteins named enhancer-binding protein (EBP)-45 and EBP-40 appear as single polypeptide bands with respective molecular masses of 45 and 40 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The TGTTTGC motif was found to be important for the hepatocyte specific expression of several genes; and in some cases, it was demonstrated that the transcription factor CCAAT/enhancer-binding protein (C/EBP) is able to bind to this sequence. In vitro experiments show that EBP-45 and EBP-40 are different from C/EBP; they also show that the two proteins interact with the TGTTTGC motif present in control regions of other hepatic genes, such as the mouse albumin enhancer eH and hepatitis B virus enhancer E elements. PMID- 1748691 TI - Pharmacological characterization of muscarinic receptor subtypes in rabbit isolated tissue preparations. AB - 1 The affinity of some muscarinic antagonists for muscarinic receptors was determined in functional isolated tissue studies in order to compare the muscarinic receptor subtypes in the rabbit. 2 Our attention was specially focused on the question of whether the muscarinic receptors mediating vasodilatation in the aorta resemble or not the ones present on the jejunum of the gastrointestinal tract. 3 Isolated aorta, jejunum, stimulated left atrium and vas deferens preparations of rabbit were investigated with the following muscarinic antagonists: atropine, pirenzepine, methoctramine (N,N'-bis[6-92 methoxybenzyl)amino hexyl]-1,8-octane-diamine tetrahydrochloride) and 4-DAMP (4 diphenylacetoxy-N-methylpiperidine methiodide). 4 The results demonstrate that the receptors on aorta are unlike those on the other rabbit tissues: pirenzepine pA2 was 6.4 on aorta but 8.1 on vas deferens; methoctramine pA2 was 5.9 on aorta but 7.1 on heart; 4-DAMP pA2 was 8.7 on aorta and 8.0 on jejunum. This raises the question: what subtype might be involved? PMID- 1748692 TI - Effect of benzylamine and its metabolites on the responses of the isolated perfused mesenteric arterial bed of the rat. AB - 1. Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme activity which can be found in the plasma membrane of rat vascular smooth muscle cells. We have investigated the possibility that the products of deamination by this enzyme, namely ammonia, hydrogen peroxide and the aldehyde, may be important in the modulation of the responses of vascular smooth muscle to extracellular stimuli. 2. The isolated perfused mesenteric arterial bed of the rat was used and dose pressure response curves (DRC) to bolus injections of adrenaline (Ad) or ATP were plotted by non-linear curve fitting. The relaxant effects of carbachol (CCh), which releases endothelium dependent relaxing factor (ERDF), were studied by co administering CCh with Ad. The effects of including the preferred SSAO substrate, benzylamine (BZ; 25 microM), in the perfusion fluid throughout the experiment and of inhibition of SSAO by treatment of rats with (E)-2-(3',4'-dimethoxyphenyl)-3 fluoroallylamine (MDL 72145; 1 mg kg-1) 1 h before dissection, have been studied. 3. Neither BZ nor SSAO inhibition affected the DRC to ATP. BZ shifted Ad responses to the left, inhibition of SSAO increased this shift indicating that the amine, but not its metabolites, were responsible for the potentiation of the responses to Ad. DRC to CCh showed a shift to the left and a significant decrease in the Hill slope with BZ, indicative of a potentiation of low doses of CCh more than high doses. Inhibition of SSAO prevented this change and so the metabolites of BZ deamination appeared to be involved in the potentiation. 4. Ammonia generated by SSAO may contribute to the production of EDRF or hydrogen peroxide may sensitize guanylate cyclase to stimulation by EDRF and so explain these findings. PMID- 1748693 TI - Hydroxyapatite-coated femoral stems. Histological analysis of components retrieved at autopsy. AB - Plasma-sprayed coating of hydroxyapatite are biocompatible and, because of their osteoconductive properties, may contribute to the early fixation of total joint prostheses. To evaluate this interface, we histologically analyzed five hydroxyapatite-coated femoral stems which, along with the surrounding bone, were retrieved from three humans at autopsy. The five femoral components had been in situ for a mean duration of twelve months (range, almost five to twenty-five months) and had been inserted for osteonecrosis (two), osteoarthrosis (two), and as an uncermented revision for failure of a cemented stem. The three patients had had a good or excellent clinical result and had died of causes unrelated to the joint arthroplasty. A coating of hydroxyapatite was identified on each stem. There was a variable amount of apposition of bone (32 to 78 per cent of available surface per section). The deposition of bone was most prominent on the surface of the prosthesis that was close to the endosteal surface of the bone, especially in areas that are predicted by Wolff's law (anterior and medial aspects of the implant, and at lateral-oblique corners). There were occasional foci of bone remodeling around the implant, including osteoclast-mediated removal of the coating of hydroxyapatite along with adjacent bone. Occasional particles of ceramic were present within macrophages in the adjacent bone marrow. Other areas showed formation of new bone with a few areas of bone directly against the metal substrate. The over-all histological features suggest mechanically stable implants with bone-remodeling at the surface of the bone-implant interface. PMID- 1748694 TI - Use of a hinged silicone prosthesis for replacement arthroplasty of the first metatarsophalangeal joint. AB - A series of ninety consecutive total joint replacements of the first metatarsophalangeal joint with a flexible hinged prosthesis was reviewed after an average duration of follow-up of three years (range, twenty-four to sixty-one months). Although subjectively the results were satisfactory in most of the patients, and pain, the most common preoperative symptom, was reduced, mechanical failure of the implant was common, as determined radiographically. The frequency of failure of the implant and the extent to which it failed were related to the length of time that the implant had been in place. The range of motion of the metatarsophalangeal joint was decreased from normal. Dorsiflexion averaged 26 degrees and plantar flexion, 18 degrees. Callosities under at least one metatarsophalangeal joint were noted in fifty (69 per cent) of the feet that had a physical examination. Pedobarographic analysis of the distribution of plantar pressure revealed that none of the patients exerted weight-bearing pressures on the affected great toe. However, the subjective results were not significantly associated with radiographic evidence of failure of the implant. Despite its success in relieving the symptoms in our patients, we have abandoned this procedure because of the high and increasing rate of failure of the implant, as demonstrated radiographically. PMID- 1748695 TI - The use of bone allografts in two-stage reconstruction after failure of hip replacements due to infection. AB - Bone allografts were used to reconstruct deficient acetabular and femoral bone in eighteen patients during two-stage revision of a hip arthroplasty that had failed due to infection. At a mean of 4.2 years after reimplantation, only two patients had had recurrence of the infection. Four patients needed another revision arthroplasty for reasons other than infection. These results suggest that allografts of bone are useful for the reconstruction of osseous deficiencies in carefully selected patients who have a hip arthroplasty after infection. The results do not support the concern that allografts that are used under these circumstances necessarily lead to a high rate of recurrence of infection. However, the long-term results of the use of allografts in hip arthroplasty after infection remain unknown. PMID- 1748696 TI - Metachronous infections in patients who have had more than one total joint arthroplasty. AB - Sixty-eight patients who had had 159 replacement arthroplasties of more than one major joint between 1975 and 1984 and who had had an infection after at least one of these procedures were identified in a retrospective review. Subsequent infection in another total joint replacement was documented in ten of these patients. The risk of development of an infection about another total joint replacement after an infection had occurred about one total joint replacement in a patient who had had more than one arthroplasty was 18 per cent, according to the survivorship-analysis method of Kaplan and Meier. Many variables that were previously thought to increase the risk of infection, such as rheumatoid arthritis, older age of the patient, previous operations, and the use of corticosteroids or immunosuppressive agents, or both, were not found to increase the risk of a subsequent infection in patients who had had more than one arthroplasty with infection of one of the arthroplasties. The recent occurrence of a major systemic infection did increase the risk of infection about the other total joint replacements. Eight of the ten subsequent joint infections were due to the same causative organism as the index infection about a total joint replacement and occurred within the first year after the index infection. The initial treatment of the index infection included specific parenteral antimicrobial therapy combined with debridement and excisional arthroplasty in forty patients, removal of the components and arthrodesis in three patients, and debridement with retention of the prosthesis in twenty-five patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748697 TI - Vehicle-moose accidents in Newfoundland. AB - During 1987 and 1988, in Newfoundland, there were 661 motor-vehicle accidents involving a moose; 133 people were injured and three died. This constitutes a major problem for the provincial health-care system. In 95 per cent of the patients who were involved in fifty-five primary collisions (the vehicle hit only the moose), the injury-severity score was less than 9 (mean and standard deviation, 3.2 +/- 4.6). There were thirty-six secondary collisions: in eighteen, the vehicle hit other objects after avoiding the moose (group A), and in the other eighteen, the vehicle hit the moose and then hit other objects (group B). In group A, the mean injury-severity score was 4.2 +/- 2.9 and in group B, it was 19.6 +/- 27.1. The three patients who died were in group B. There were more injuries to the thorax, thoracolumbar spine, and abdomen in group B than in the single-collision groups (primary-collision group and group A). PMID- 1748698 TI - Interlocking intramedullary nailing for ipsilateral fractures of the femoral shaft and distal part of the femur. AB - A review of the data on 684 fractures of the femur that had been treated with intramedullary nailing led to the identification of twenty-three patients who had had a fracture of the shaft of the femur with an accompanying ipsilateral supracondylar fracture (twelve patients, group I) or a concomitant ipsilateral intercondylar fracture (eleven patients, group II). The group-I fractures had been treated with interlocking nailing without supplemental fixation. In group II, ten fractures were stabilized with interlocking nailing and supplemental screw fixation and one, with interlocking nailing and a supplemental plate and screws. The average time to union for all fractures was nineteen weeks (range, twelve to thirty-six weeks), and the average duration of clinical and radiographic follow-up was thirty months (range, nine to fifty-nine months). In group I, alignment of the femur was within 5 degrees of normal in ten of the twelve fractures. In group II, seven intra-articular fractures healed in anatomical alignment, three had slight articular displacement (1.0 to 3.0 millimeters), and one had displacement of more than 3.0 millimeters. The average range of motion of the knee at the most recent follow-up was 0 to 120 degrees in group I and 0 to 115 degrees in group II. Two patients (both in group II) needed a reoperation for a previously unrecognized fracture of a femoral condyle in the coronal plane; post-traumatic arthritis developed in both. No patient in either group had loss of fixation or failure of the implant. We concluded that ipsilateral diaphyseal, supracondylar, and intercondylar fractures of the femur can be adequately stabilized with interlocking nailing and supplemental intercondylar screw fixation. The presence of a fracture in the coronal plane of a femoral condyle (AO type-B3 and type-C3 injuries) is a relative contraindication to the use of this technique. PMID- 1748699 TI - Pericardial tamponade secondary to perforation by central venous catheters in orthopaedic patients. AB - Pericardial tamponade from an indwelling central venous catheter developed in four orthopaedic patients. Two of these patients died acutely, and the other two sustained severe anoxic brain injury. The early signs of tamponade include tachycardia, hypotension, and increased central venous pressure. The outcome most often is fatal. When a central venous catheter has been placed incorrectly or has migrated, it can perforate the heart and produce pericardial tamponade. To avoid this complication, the tip of the catheter must be placed within the superior vena cava rather than the right atrium, and the position of the catheter must be ascertained with a radiograph of the chest. Prompt recognition and treatment of pericardial tamponade are imperative if a disastrous outcome is to be prevented. PMID- 1748700 TI - Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. AB - We evaluated specimens obtained from the biopsy of spontaneously ruptured tendons in 891 patients who were treated between 1968 and 1989. The specimens, which were removed at the time of repair, included 397 Achilles tendons, 302 biceps brachii tendons, forty extensor pollicis longus tendons, eighty-two quadriceps tendons and patellar ligaments, and seventy other tendons. Age and sex-matched control specimens, from 445 tendons taken at the time of death from the cadavera of previously healthy individuals who died accidentally, also were obtained and evaluated. The histopathological analyses of the specimens included light and polarized light microscopy and scanning and transmission electron microscopy. A healthy structure was not seen in any spontaneously ruptured tendon, but two thirds of the control tendons were structurally healthy (p less than 0.001). There were characteristic histopathological patterns in the spontaneously ruptured tendons. Most (97 per cent) of the pathological changes were degenerative; they included hypoxic degenerative tendinopathy, mucoid degeneration, tendolipomatosis, and calcifying tendinopathy, either alone or in combination. These changes were also found in 34 per cent of the control tendons, but significantly less frequently (p less than 0.001). In the other twenty-six ruptured tendons (3 per cent), the pathological change was an intratendinous foreign body, rheumatoid tendinitis, a xanthoma, a tumor, or a tumor-like lesion such as an intratendinous ganglion. The findings clearly indicate that, at least in an urban population, degenerative changes are common in the tendons of people who are older than thirty-five years and that these changes are associated with spontaneous rupture. PMID- 1748701 TI - The shoulder girdle in ankylosing spondylitis. AB - We report the clinical findings in the shoulders of fifty-two patients who had ankylosing spondylitis. The three major patterns that were found included limitation of scapulothoracic motion (forty-one patients), acute inflammatory arthropathy of the sternoclavicular or acromioclavicular joint (six patients), and severe restriction of glenohumeral motion (five patients). Although radiographic abnormalities were common, they correlated with the clinical findings in only minor respects. PMID- 1748702 TI - X-chromosome inactivation in patients who have pigmented villonodular synovitis. AB - We performed a histological examination and DNA analysis on samples of tissue from a forty-seven-year-old woman who had a clinical diagnosis of pigmented villonodular synovitis. The histological examination confirmed the diagnosis. The evaluation of the samples of tissue with preferential X-chromosome inactivation analysis (a molecular biological method for the study of clonality in tumors) showed that the lesion was polyclonal in origin. We concluded, therefore, that pigmented villonodular synovitis is more likely to be a reactive process than a true neoplasm. PMID- 1748703 TI - Extrusion of an intervertebral disc associated with traumatic subluxation or dislocation of cervical facets. Case report. PMID- 1748704 TI - Fractures of the shaft of the femur. PMID- 1748705 TI - Report of the 1991 ABC Traveling Fellows. A scientific presentation. PMID- 1748706 TI - Perioperative blood loss associated with total knee arthroplasty. A comparison of procedures performed with and without cement. PMID- 1748707 TI - Idiopathic osteonecrosis of the patella: an unusual cause of pain in the knee. A case report. PMID- 1748708 TI - The effect of intravenous fixed-dose heparin during total hip arthroplasty on the incidence of deep-vein thrombosis. A randomized, double-blind trial in patients operated on with epidural anesthesia and controlled hypotension. PMID- 1748709 TI - Tests for posterolateral instability of the knee in normal subjects. Results of examination under anesthesia. PMID- 1748710 TI - Ingrowth and formation of bone in defects in an uncemented fiber-metal total hip replacement model in dogs. PMID- 1748711 TI - Indications for magnetic resonance imaging. PMID- 1748712 TI - Dedifferentiated chondrosarcoma. Report of an unusual case. PMID- 1748713 TI - Radiographic assessment of instability of the knee due to rupture of the anterior cruciate ligament. A quadriceps-contraction technique. PMID- 1748714 TI - IL-1 beta and prostaglandins regulate integrin mRNA expression. AB - The purpose of this study was to examine the effects of IL-1 beta on integrin expression in MG-63 human osteosarcoma cells. Human recombinant IL-1 beta (rIL-1 beta) produced significant increases in both alpha 2- and alpha 5-subunit mRNA levels, as well as a smaller increase in alpha v-subunit mRNA. In contrast, IL-1 beta decreased alpha 4-subunit mRNA levels by approximately 30% relative to untreated controls. These findings suggest that human IL-1 beta differentially regulates expression of integrins. When cultures were treated with both IL-1 beta and the cyclooxygenase inhibitor, indomethacin, the expression of alpha 2-, alpha 5-, and alpha v-subunit mRNA levels were dramatically increased relative to untreated controls; co-treatment with 0.5 mM prostaglandin E2 (PGE2) partially reversed this effect. Indomethacin alone did not affect integrin mRNA levels. Treatment with IL-1 beta or IL-1 beta + indomethacin also induced significant changes in MG-63 morphology (i.e., increased cell elongation) and increased the ability of cells to contract collagen gels. PGE2 reversed the above effects on cell morphology and gel contraction. These findings indicate that (a) IL-1 beta differentially regulates the expression of integrins and (b) that PGE2, which is induced by IL-1 beta, may provide a negative feedback loop which counteracts the stimulatory effect of IL-1 beta on integrin gene expression. It is suggested that products of inflammation may affect cell behavior by differentially regulating the expression of various integrins. PMID- 1748715 TI - Effect of tunicamycin on glycosylation of a 50 kDa protein and thermotolerance development. AB - We investigated whether or not a 50 kDa glycoprotein might play an important role in protein synthesis-independent thermotolerance development in CHO cells. When cells were heated for 10 min at 45.5 degrees C, they became thermotolerant to a heat treatment at 45.5 degrees C administered 12 hr later. The thermotolerance ratio at 10(-3) isosurvival was 4.4. The cellular heat shock response leads to enhanced glycosylation of a 50 kDa protein. The glycosylation of proteins including a 50 kDa glycoprotein was inhibited by treatment with various concentrations of tunicamycin (0.2-2 micrograms/ml). The development of thermotolerance was not affected by treatment with tunicamycin after the initial heat treatment, although 2 micrograms/ml tunicamycin inhibited glycosylation by 95%. However, inhibiting protein synthesis with cycloheximide (10 micrograms/ml) after the initial heat treatment partially inhibited the development of thermotolerance. Nevertheless, there was no further reduction of thermotolerance development by treatment with a combination of 2 micrograms/ml tunicamycin and 10 micrograms/ml cycloheximide. These data suggest that development of thermotolerance, especially protein synthesis-independent thermotolerance, is not correlated with increased glycosylation of the 50 kDa protein. PMID- 1748716 TI - Recessive (mediator-) revertants from c-H-ras oncogene-transformed NIH 3T3 cells: tumorigenicity in nude mice and transient anchorage and serum independence of the recovered tumor cells in culture. AB - We have reported earlier the isolation of two recessive, serum- and anchorage dependent revertants (R116 and R260) from a c-H-ras oncogene-transformed NIH 3T3 line. In both revertants, the oncogene was fully expressed and fusion of either revertant with (untransformed) NIH 3T3 cells, or of the two revertants with one another, resulted in transformed progeny. These, and other data, indicated that the transforming activity of the oncogene was impaired in the two revertants in consequence of defects in distinct genes needed to mediate this activity. We report here that neither revertant could be re-transformed by the K-ras or N-ras oncogene (though they could be re-transformed by several other oncogenes). The two revertants turned out to be tumorigenic in nude mice (though less so than the parental transformed cells). The tumor cells, as recovered, formed foci and had a transformed morphology and a greatly diminished serum and anchorage dependence. Growth of the cells in culture (for 20 passages) resulted in their regaining the characteristics (i.e., anchorage and serum dependence) of cultured R116 and R260 cells. Proliferation of the cells in nude mice was not accompanied by a change in the level of ras oncogene expression or in gene amplification, at least as manifested in the lack of appearance of double-minute chromosomes. The addition of the growth factors TGF alpha and beta to the medium of either revertant did not support anchorage-independent growth. PMID- 1748717 TI - Dexamethasone and retinoic acid regulate the expression of epidermal growth factor receptor mRNA by distinct mechanisms. AB - Retinoic acid and dexamethasone have antagonistic effects on epidermal growth factor (EGF) receptor expression in fetal rat lung (FRL) cells: Receptor synthesis is enhanced by retinoic acid and reduced by dexamethasone. In the presence of actinomycin D, neither agent has the capacity to modify receptor synthesis or 125I-EGF binding capacity. Northern blot analysis demonstrates a tenfold increase in EGF mRNA following retinoic acid treatment and a 60% decrease in receptor message levels after dexamethasone treatment. To dissect the mechanisms of these effects, the expression of mRNA was separated from effects requiring protein synthesis by the use of cycloheximide and actinomycin D. Ligand binding, EGF receptor protein synthesis, and mRNA levels were measured in cultures of FRL cells that were incubated with retinoic acid or dexamethasone in the presence of cycloheximide, then washed and reincubated with fresh media containing actinomycin D, but not retinoic acid, dexamethasone, or cycloheximide. The results demonstrate that dexamethasone reduces the expression of EGF receptor mRNA in the absence of protein synthesis. In contrast, the mechanism by which retinoic acid increases the expression of EGF receptor mRNA requires protein synthesis. These data indicate that, in FRL cells, dexamethasone negatively regulates EGF receptor mRNA in a direct manner, while retinoic acid controls transcription of an intermediate protein, possibly a transcription factor, that subsequently increases transcription of receptor message. PMID- 1748718 TI - Insulin-like growth factor 1, insulin, and progesterone induce early and late increases in Xenopus oocyte sn-1,2-diacylglycerol levels before meiotic cell division. AB - After a 3 to 6 hour incubation, addition of progesterone (the most effective), insulin-like growth factor 1 (IGF-1; the second most effective), or insulin induces meiotic cell division in Xenopus oocytes. Measurement of an endogenous activator of protein kinase C, sn-1,2-diacylglycerol (DAG), by an enzymatic method recording mass demonstrates that all three hormones alter DAG levels. Five seconds after addition, only progesterone transiently reduces DAG levels by about 25%. At 15 minutes after addition, all three hormones produce a peak of DAG (115% to 160% of control values), with the more effective hormones producing a larger increase in DAG. Insulin produces the smallest DAG increase, but the DAG release is longer lasting. Finally, all three hormones induce a second peak in DAG levels just before white spot appearance (at 0.85 GVBD50, where 1.0 GVBD50 is when 50% of the cells have divided). With these data and since an activator of protein kinase C, a phorbol ester, has been found to induce meiosis, the kinase may play a role in early proliferative events at the plasma membrane and in late events at the nucleus. PMID- 1748719 TI - Clustering of erythrocytes by fibrinogen is inhibited by carnitine: evidence that sulfhydryl groups on red blood cell membranes are involved in carnitine actions. AB - Carnitine is bound by intact red blood cells, by red blood cell ghosts, and by glutaraldehyde-fixed human erythrocytes in a non-saturable, temperature-dependent manner. Binding of carnitine by these preparations is blocked by sulfhydryl reagents. Incubation or preincubation of red blood cell preparations with carnitine inhibits the aggregation of erythrocytes otherwise elicited by fibrinogen. Identical effects are obtained with red blood cell ghosts. In contrast, choline, even at high concentrations, is inactive in preventing the aggregation of erythrocytes. We discuss possible mechanisms by which carnitine favors the dispersion of red blood cells, and we present data indicating that sulfhydryl groups on erythrocyte membranes are required to permit these carnitine actions to be manifested. PMID- 1748720 TI - Isoprenoids and astroglial cell cycling: diminished mevalonate availability and inhibition of dolichol-linked glycoprotein synthesis arrest cycling through distinct mechanisms. AB - Primary astroglial cultures were used to compare the relationships to cell cycling of dolichol-linked glycoprotein synthesis, and of availability of mevalonate, the precursor of dolichol and other isoprenoid lipids. With shift-up to 10% serum (time 0) after 48 h of serum depletion, the proportion of cells in S phase (bromodeoxyuridine immunofluorescence) remained under 15% for 12 h, then increased by 20 h to 72 +/- 10%; DNA synthetic rates (thymidine incorporation) increased 5-fold. S phase transition was prevented by addition at 10-12 h of tunicamycin, an inhibitor of transfer of saccharide moieties to dolichol. Mevinolin, an inhibitor of mevalonate biosynthesis, also blocked cycle progression when added at this time. However, mevinolin markedly inhibited the isoprenoid pathway, as reflected by over 90% reduction of sterol synthesis, without inhibiting net glycoprotein synthesis. Removal of mevinolin after a 24 h exposure delayed S phase until 48 h, following recovery of sterol synthesis, even though kinetics of glycoprotein synthesis were unaffected. Tunicamycin removal after 24 h spared sterol synthesis, but caused delay of S phase until 72 h, following recovery of glycoprotein synthesis. In mevinolin-treated cultures, S phase transition was restored by 1 h of exposure to mevalonate at 10 h, although cycling was thereby rendered sensitive to inhibition by cycloheximide and by tunicamycin. Cell cycle progression following hydroxyurea exposure and release was unaffected by mevinolin, tunicamycin, or cycloheximide. Thus, in these developing astroglia, mevalonate and its isoprenoid derivatives have at least two cell cycle-specific roles: dolichol-linked glycoprotein synthesis is required at or before the G1/S transition, while a distinct mevalonate requirement is apparent also in late G1. PMID- 1748721 TI - Sphingosine reverses growth inhibition caused by activation of protein kinase C in vascular smooth muscle cells. AB - In certain cell systems, including neonatal vascular smooth muscle (VSM) cells, phorbol esters are growth inhibitory. Here we show that 1,2-dioctanoyl-sn glycerol (DiC8), when added 2 h after alpha-thrombin, reverses by greater than 95% the induction of DNA synthesis in VSM cells by alpha-thrombin. Sphingosine, a naturally occurring lysosphingolipid inhibitor of protein kinase C, and its synthetic analogues N-acetylsphingosine and C11-sphingosine were used to investigate this phenomenon further. Neither phorbol 12-myristate 13-acetate (PMA;200 ng/ml) nor sphingosine (up to 10 microM) alone had any effect upon basal DNA synthesis in VSM cells. Like DiC8, PMA totally blocked the induction of DNA synthesis by alpha-thrombin. This inhibitory effect of PMA was reversed by sphingosine in a dose-dependent manner with complete reversal at 10 microM. Neither N-acetylsphingosine nor C11-sphingosine exhibited any effect on DNA synthesis in VSM cells. The effect of sphingosine and its analogues on the activity of protein kinase C extracted from VSM cells was measured by histone III S phosphorylation. Protein kinase C activity was inhibited 50% by 300 microM sphingosine, but less than 15% by similar concentrations of N-acetylsphingosine and C11-sphingosine. To assess the effects of sphingosine and analogues on protein kinase C in intact cells, we examined the effect of the lipids on [3H]phorbol dibutyrate binding. Sphingosine (at greater than 5 microM), but not N acetylsphingosine or C11-sphingosine, blocked [3H]phorbol dibutyrate binding in a dose- and time-dependent fashion. Thus the mechanism of growth inhibition by DiC8 and PMA in neonatal VSM cells appears to be through activation of protein kinase C by these compounds. Sphingosine reverses this growth inhibition through interference with the binding to protein kinase C of phorbol esters or other activators of this enzyme. PMID- 1748722 TI - Regulation of glucose uptake by stressed cells. AB - Lactate production by BHK cells is stimulated by arsenite, azide, or by infection with Semliki Forest virus (SFV). In the case of arsenite or SFV infection, the increase correlates approximately with the increase in glucose transport as measured by uptake of [3H] deoxy glucose (dGlc); in the case of azide, the increase in lactate production exceeds that of glucose transport. Hence glucose utilization by BHK cells and its stimulation by anaerobic and other types of cellular stress is controlled at least in part at the level of glucose transport. The glucose uptake by BHK cells is also stimulated by serum and by glucose deprivation. In these circumstances, as with arsenite, stimulation is reversible, with t1/2 of 1-2 hours; stimulation is compatible with a translocation of the glucose transporter protein between an intracellular site and the plasma membrane (shown here for serum and previously for arsenite). The surface binding and rate of internalization of [125I]-labelled transferrin and [125I] alpha 2 macroglobulin was studied to determine whether changes in glucose transport are accompanied by changes in the surface concentration or rate of internalization of membrane proteins. The findings indicate that changes in glucose transport do not reflect a consistent and general redistribution of membrane receptors. Taken together, the results are compatible with the proposal that BHK cells exposed to stimuli like insulin or serum, or to stresses like arsenite, azide, SFV infection, or deprivation of glucose, respond in the same manner: namely, by an increased capacity to transport glucose brought about by reversible and specific translocation of the transporter protein from an (inactive) intracellular site to the plasma membrane. PMID- 1748723 TI - Changes in cobalamin metabolism are associated with the altered methionine auxotrophy of highly growth autonomous human melanoma cells. AB - Our aim was to identify the biochemical defect responsible for the inability of highly growth autonomous human tumor cells to proliferate in culture medium devoid of methionine, but containing homocysteine and 5-methyletrahydrofolic acid. We have adopted the terms "homocysteine-responsive" and "homocysteine nonresponsive" to describe cells which can or cannot proliferate in methionine free homocysteine-supplemented medium. Using a panel of genetically related homocysteine-responsive and -nonresponsive human melanoma cell lines, the results from a number of experiments indicate that acquisition of the "homocysteine nonresponsive phenotype" is associated with the reduced intracellular accumulation of methyl-cobalamin, a critical cofactor of the methionine synthase enzyme. When in vitro methionine synthase assays were performed in the presence of exogenously added methyl-cobalamin, specific methionine synthase activity in extracts obtained from homocysteine-responsive cells was only twofold greater than that observed with extracts prepared from homocysteine-nonresponsive cells. However, when exogenous methyl-cobalamin was omitted from the enzyme assays, methionine synthase activity in extracts derived from homocysteine-nonresponsive cells was dramatically reduced, compared with the small decrease observed with homocysteine-responsive cell extracts. Compared with their homocysteine responsive counterparts, homocysteine-nonresponsive cells exhibited increased levels of cobalamin efflux and decreased intracellular accumulation of methyl cobalamin. There was a clear relationship between the abilities of these related melanoma cell lines to proliferate in methionine-free homocysteine-supplemented medium, and the extent of cobalamin loss and capacity of exogenously added methyl cobalamin to stimulate in vitro methionine synthase activity. These results indicate a link between alterations in the intracellular trafficking and/or metabolism of cobalamin and the increased growth autonomy of human melanoma cells. PMID- 1748725 TI - Journal of Chromatography. Cumulative author, subject and compound indexes. Volumes 501-550 (1990-1991). PMID- 1748724 TI - Adipogenic activity produced by hepatocyte-derived cell lines and by normal hepatocytes in primary culture. AB - Culture media conditioned by several hepatocyte derived cell lines were analyzed for their ability to stimulate adipose differentiation of the adipogenic cell line 1246. The results presented here show that culture media from HepG2 and Hep3B cell lines contain a high level of the activity, whereas media from hepatoma and hepato adenocarcinoma cell lines Huh-7, PLC/PRF/5, and SK-Hep-1 do not contain adipogenic activity. Conditioned medium from HepG2 cells also stimulated differentiation of 3T3-L1 cells and of rat epididymal adipocyte precursors in primary culture. Partial biochemical characterization of the adipogenic activity carried out using HepG2 conditioned medium indicates that the hepatocyte derived adipogenic factor has an apparent molecular weight between 445 and 232 kDa, is destroyed by treatment at 100 degrees C, with protease, with 2 mercaptoethanol and in acidic conditions. The activity is stable at alkaline pH. Culture media conditioned by normal rat hepatocytes in primary culture also contained adipogenic activity. In contrast, medium conditioned by primary culture of nonhepatocyte cell also isolated from liver was deprived of this activity. The data presented in this paper suggest that hepatocytes could be a physiological site of production of adipogenic activity. PMID- 1748726 TI - Intraorbital transection of the rabbit optic nerve: consequences for ganglion cells and neuroglia in the retina. AB - Rabbit retinae were stained with antibodies to glial fibrillary acidic protein (GFAP) at various times up to 5 months after complete unilateral intraorbital optic nerve transection, which is known to induce degeneration of ganglion cell axons and perikarya in the retina. A transient immunoreactivity for GFAP was observed in Muller glial cells that normally lack this marker. Muller-cell GFAP immunoreactivity became detectable 4 days after the lesion, but Muller cells were no longer labeled 3 months later. GFAP-labeled astrocytes located in the nerve fiber layer showed no change in immunoreactivity at any stage after transection. Application of horseradish peroxidase to the left and right superior colliculus of a rabbit whose optic nerve had been transected unilaterally 2 years before confirmed the completeness of the transection. Yet electron microscopy showed the presence of some healthy-looking ganglion cell axons in the lesioned retina, although these cells were deprived of their target. Labeling retinal wholemounts with neurofilament antibodies confirmed the presence of some ganglion cell axons and perikarya in the retina more than 2 years after transection. The course of these axons suggested that they were remnants of axons. Using antibodies to galactocerebroside (GC) we found that, as in the normal rabbit, these persisting ganglion cell axons were myelinated in the medullary rays. Although many ganglion cell axons had disappeared after 2 years, the number of neuroglial cells (including astrocytes and oligodendrocytes) present in the medullary ray region was not altered. The cell bodies of some oligodendrocytes were covered with a myelin sheath, an aberrant feature not seen normally. PMID- 1748727 TI - Early development of the retinal line of decussation in normal and albino ferrets. AB - This work describes the retinal origin of the crossed and uncrossed projections in newborn, 9-day-old and adult normally pigmented and albino ferrets. Horseradish peroxidase (HRP) was injected unilaterally into the thalamic and midbrain visual centers of ferrets to label retinal ganglion cells retrogradely. In normally pigmented adults, the retinal line of decussation was sharp and passed through the area centralis. Ganglion cells with uncrossed axons occupied the entire temporal retina. In albino adults, ganglion cells with uncrossed axons were distributed in the periphery of the temporal retina away from the area centralis. In the normally pigmented adults, about 11% of the retinal ganglion cells had uncrossed axons compared to about 4% in the albinos. At birth, normally pigmented ferrets had a sharp line of decussation with most (about 98%) uncrossed ganglion cells found in the temporal retina. In the newborn albinos, most uncrossed ganglion cells were in the temporal retina (about 89%), but there were many fewer than in the normal neonates and, as in the albino adults, the uncrossed ganglion cells were distributed along the temporal most margin of the retina. In the normal neonates, about 11% of the ganglion cells had uncrossed axons, compared to about 3% in the albino neonates. The area centralis and visual streak were not evident until 9 days after birth. From these results we conclude that the retinal line of decussation is essentially mature by birth in the ferret, and the degree of the albino's abnormality is as extreme in neonates as in adults. The retinal decussation is virtually mature at a stage of development when the crossed and uncrossed retinal afferent axons are completely intermingled in their target nuclei and prior to the onset of significant retinal ganglion cell loss. PMID- 1748728 TI - Neuromuscular organization of the buccal system in Aplysia californica. AB - The intrinsic muscles and peripheral nerves in the buccal system of the sea hare Aplysia californica were studied to build a foundation on which to base future investigations of feeding in intact animals. A detailed description of the bilaterally paired intrinsic muscles is given identifying previously unreported muscles. Each of the six buccal nerves (n1-n6) and the cerebrobuccal connective (CBC) have been characterized in several respects. Cell bodies in the buccal ganglion with projections into each of the buccal nerves have been identified via the cobalt backfilling technique. All nerves contain axons of cell bodies in the ipsilateral as well as the contralateral ganglia. For each nerve, there is a consistent pattern in the distribution of cell bodies in the paired ganglia with the number of cell bodies in the contralateral ganglion being less than or equal to the number in the ipsilateral ganglion. Although the total number of backfilled cell bodies varies among the nerves, their size ranges are similar with the majority being small. Nerves 1, 2, 4, 5, and 6 provide motor innervation to the intrinsic buccal muscles in varying degrees with nerve 4 supplying all the intrinsic muscles; nerve 2 supplies only one. The axon composition of each nerve was scrutinized and revealed large numbers of axon profiles, the majority of which were less than 2 microns in diameter. The present study provides a framework for analysis of feeding behavior in Aplysia californica. PMID- 1748729 TI - Comparison of serotonin 5-HT1 receptors and innervation in the visual cortex of normal and dark-reared cats. AB - The visual cortical serotoninergic system was compared in normal and dark-reared cats to determine whether visual experience is necessary for its normal development. In vitro receptor binding of [3H]5-HT indicated an increase in 5-HT1 receptor number in dark-reared cats with no change in affinity. This elevation was specific to the visual cortex and no changes were found in the frontal cortex as a result of dark rearing. Autoradiographic histology revealed that in the normal cat visual cortex, 5-HT1 receptors were present in all cortical layers and were slightly more dense in supragranular and infragranular layers. In dark reared cats, there was a marked elevation in receptor density in supragranular and infragranular layers and little change within layer IV. Immunohistochemical techniques (anti-5-HT) were used to compare serotoninergic innervation in the visual cortex of normal and dark-reared cats. In normal cat visual cortex, serotonin fibers were most dense in the superficial layers (I-III), least dense in layers IV and VI, and intermediate in layer V. No differences were found between normal and dark-reared cats in the laminar distribution or density of serotoninergic innervation. These results indicate that visual experience is necessary for the normal development of the visual cortical serotonin system. The findings that the effects of dark rearing were specific to the visual cortex and that within the visual cortex these effects were specific to supra- and infragranular layers are consistent with a possible role for serotonin in the prolonged physiological plasticity that occurs in the visual cortex of dark reared cats. PMID- 1748730 TI - Medial terminal nucleus terminals in the nucleus of the optic tract contain GABA: an electron microscopical study with immunocytochemical double labeling of GABA and PHA-L. AB - In this study the medial terminal nucleus (MTN) projection to the nucleus of the optic tract (NOT) was investigated in pigmented rats at the light and electron microscopical levels with a new combination of techniques. MTN terminals were anterogradely labeled with Phaseolus vulgaris-leucoagglutinin (PHA-L). Preembedding immunocytochemistry, followed by gold intensification, was used to visualize PHA-L. Postembedding immunocytochemistry with 15 nm immunogold particles was carried out to demonstrate the inhibitory neurotransmitter gamma aminobutyric acid (GABA). Both PHA-L and GABA labeling can be easily discriminated at the electron microscopical level even when present in the same neuronal profiles. Light microscopically MTN-NOT fibers proved to have several branches with many varicosities. MTN terminals were found concentrated in terminal fields. Electron microscopically, it was shown that MTN boutons display characteristics resembling F-type terminals, i.e., terminals with dark mitochondria, pleomorphic vesicles, and symmetrical synapses. All NOT afferents originating from the MTN contained GABA and made multiple contacts exclusively with GABA negative NOT somata and dendrites. These results indicate the existence of a strong and direct inhibitory input onto GABA negative projection neurons in the NOT. This substantiates earlier physiological and morphological reports. It was further demonstrated that the location and organization of MTN terminals in the neuropil differ from that of the retinal input: MTN terminals are largely separated from retinal terminals. MTN terminal fields contain large amounts of GABA positive F terminals in contrast to retinal terminal areas. MTN terminals take part in irregularly shaped agglomerations of terminals, which contain many F terminals and dendritic processes and are surrounded by a glial sheet. Retinal terminals are found grouped together in small circular arrangements contacting a central dendrite. PMID- 1748731 TI - Morphology and mosaics of VIP-like immunoreactive neurons in the retina of the rhesus monkey. AB - Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that has been demonstrated to reside in cells ( = VIP+ cells) of the retinae of various vertebrate species. In an attempt to study the morphology and distribution of VIP+ cells in the retina of the rhesus monkey in more detail, we subjected VIP+ cells observed in cryostat sections or wholemounts rhesus monkey retinae to a quantitative analysis. VIP+ cells were found to reside in the innermost row of the inner nuclear layer (INL) and in the ganglion cell layer (GCL) in similar numbers (estimate: 50 cells/mm2 at 6-10 mm eccentricity each) and only on rare occasions (12% of all VIP+ cells) in varying positions within the inner plexiform layer (IPL). Somata of VIP+ cells were circular and had a mean diameter of 9.1 microns. They gave rise to 1-3 main dendrites, which were usually oriented toward the IPL. Main dendrites ramified widely into thin fibers (dendritic field diameter less than = 1 mm), carrying varicose swellings. The fibers that contributed to one and the same plexus of VIP+ fibers preferred the middle third of the IPL, independent of the positions of the parent somata. A quantitative analysis of nearest-neighbour distances in the retinal wholemount preparation suggested that VIP+ cells in the GCL and in the INL might be distributed according to 2 independent mosaics. A comparison with Golgi-stained material leads to the tentative equation of VIP+ cells with the "spiny" A12 amacrine cell of Mariani ('90). Whereas the low density and large dendritic field size of VIP+ cells might suggest a more widespread function, the varicose dendritic morphology seems to be more compatible with functionally independent dendritic subunits mediating localized effects. PMID- 1748732 TI - Functionally distinct subdivisions of the macroglomerular complex in the antennal lobe of the male sphinx moth Manduca sexta. AB - Each antennal lobe in the brain of a male moth has a distinctive neuropil structure, the macroglomerular complex (MGC), which is specialized for primary processing of information about the conspecific female sex-pheromone blend. Olfactory interneurons with dendritic arborizations in the MGC were examined by means of tandem intracellular recording and staining with Lucifer Yellow. Neurons that responded selectively to stimulation of the antenna with the major pheromone component, (E,Z)-10,12-hexadecadienal, had arborizations that were restricted to a toroidal subdivision (the "toroid") of the MGC. Similarly, neurons that responded selectively to antennal stimulation with (E,Z)-11,13-pentadecadienal, a more stable mimic of a second essential but chemically unstable pheromone component, (E,E,Z)-10,12,14-hexadecatrienal, had arborizations confined to a globular subdivision (the "cumulus") of the MGC situated more proximally to the antennal nerve input. One neuron that responded to both of these stimuli clearly had arborizations in both subdivisions of the MGC. These anatomically distinct subdivisions of the MGC thus appear also to be functionally separate regions of pheromone-processing neuropil. PMID- 1748733 TI - Somatotopy of spinal nociceptive processing. AB - Relatively little is known about the spatial organization of spinal nociceptive processing. This study has employed the expression of c-fos-like protein as a marker for neuronal activity and has analyzed the patterns of immunoreactivity seen within the rodent spinal cord following noxious mechanical stimulation of various portions of one hindlimb. The results indicate that noxious mechanical stimulation induces distinct, somatotopic patterns of immunolabeling in laminae I IV. Individual digits of a foot are represented medially in the dorsal horn over a short rostrocaudal distance, with the most lateral digit represented approximately one segment caudal to the most medial digit. Representation of the hip region is more lateral, is centered at L2, and extends rostrocaudally over many segments. The patterns of neuronal excitation seen in laminae V-IX following noxious peripheral stimulation were similar to those noted in laminae I-IV but were less tightly organized. C-fos-like immunoreactivity was noted both medially and laterally in the deeper laminae following stimulation of any portion of the hindlimb, but stimulation of different areas produced different columns of labeled cells extending from the superficial dorsal horn into lamina VII. In the rostrocaudal direction, immunolabeling in lamina V-IX was maximal at the same segmental level as in laminae I-IV, but the more ventral laminae exhibited increases in c-fos-like immunoreactivity over longer rostrocaudal distances. Experiments in spinally transected animals indicated that long, descending pathways contributed little or nothing to the pattern of immunolabeling. The results of this study imply that spinal nociceptive processing is spatially organized not only in laminae I-IV, but also in more ventral regions of the spinal cord. PMID- 1748734 TI - Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum. AB - Angiotensin II (Ang II) binding sites were localized in the thalamus, basal ganglia, midbrain, and pons of the human central nervous system by in vitro autoradiography, employing 125I-[Sar1, Ile8]angiotensin II as the radioligand. High-density binding occurs in the substantia nigra pars compacta, the interpeduncular nucleus and two of the raphe nuclei, the raphe magnus, and median raphe nucleus. Moderate densities occur in the caudate nucleus, putamen, bed nucleus of the stria terminalis, rostral linear nucleus, caudal linear nucleus, dorsal and paramedian raphe nuclei, locus coeruleus, and region of the subcoeruleus, oral dorsal paramedian nucleus, and A5/periolivary region. Low levels occur in the region between the subthalamic nucleus and the zona incerta, the mediodorsal thalamic nucleus, the central gray, the lateral and medial parabrachial nuclei, and the molecular layer of the cerebellum. The high density of Ang II receptor binding in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons. The binding in this site, and in the striatum, is not observed in any of the other species we have studied. It displays similar pharmacological characteristics to the Ang II receptor binding site in other regions of the human brain. Overall we demonstrate a discrete pattern of Ang II receptor binding sites in the human brain, which shows a high correlation with the distribution observed in other mammalian species. PMID- 1748735 TI - Topography and ultrastructure of sensory nerve endings in the glans penis of the rat. AB - The aim of the present study was to describe the types and location of sensory nerve endings in the glans penis of the rat on the basis of light and electron microscopy. Free nerve endings are abundant throughout the glans and are derived from either thinly myelinated A delta or unmyelinated C fibers. The free nerve endings derived from A delta fibers often extend into the epidermis as far as the granular layer and exhibit buttonlike terminal thickenings. The distal urethra contains many free nerve endings from C fibers. Numerous lamellated corpuscles are present. Each corpuscle, innervated by one or two medium diameter myelinated nerve fibers, consists of 4-10 spiralling and intertwined inner cores enveloped by Schwann cell lamellae. The corpuscles are usually enclosed by a perineural capsule, although some located near the epidermis lack a capsule. Lamellated corpuscles in the superficial dermis are located adjacent to but not directly under a penile spine and change their orientation when the glans is erect. The dermal papillae of the penile spines are devoid of any neural structure. Lamellated corpuscles are also located within the trabeculae of the corpus spongiosum glands and in the lamina propria of the urethra. Occasionally, unmyelinated nerve bundles are seen inside these corpuscles. Ruffini corpuscles are few in number and are located in the deep connective tissue near the os penis. They have an incomplete connective tissue capsule and the nerve terminals are anchored between collagen fiber bundles. No Merkel nerve endings, Meissner, or Vater-Pacini corpuscles were found in any of the sections. We conclude that the glans penis of the rat contains a sensory receptor complement that is generally similar to the human glans penis but is unlike the glabrous and hairy skin. PMID- 1748736 TI - Auditory, electrosensory, and mechanosensory lateral line pathways through the forebrain in channel catfishes. AB - The forebrain auditory, electrosensory, and mechanosensory lateral line pathways in the channel catfish, Ictalurus punctatus, were examined by applying the fluorescent tracer DiI to 1) the auditory part of the torus semicircularis, 2) the electrosensory part of the torus semicircularis, 3) the lateral preglomerular nucleus, and 4) the anterior tuberal nucleus. Three distinct pathways ascend from the torus semicircularis to the telencephalon; they course through either 1) the lateral preglomerular nucleus of the posterior tuberculum, 2) the anterior tuberal nucleus of the hypothalamus, or 3) the central posterior nucleus of the dorsal thalamus. The anatomical data suggest that each of these ascending pathways carries information from more than one sensory modality. The lateral preglomerular nucleus receives an electrosensory input from nucleus electrosensorius in the diencephalon, but it also receives auditory and mechanosensory inputs directly from the torus semicircularis. The anterior tuberal and central posterior nuclei receive primarily auditory and mechanosensory, but also minor electrosensory, inputs. The efferent projections of the central posterior nucleus are presently unknown, but the lateral preglomerular and anterior tuberal nuclei project to nonoverlapping portions of the telencephalon. A cladistic analysis of these indirect torotelencephalic pathways reveals that 1) the pathway through the dorsal thalamus is probably a primitive character for gnathostomes, 2) a well-developed pathway through the posterior tuberculum is probably a derived character for actinopterygian fishes, 3) the pathway through nucleus electrosensorius is probably a derived character for catfishes and gymnotoid teleosts, and 4) auditory pathways through the hypothalamus probably evolved independently in catfishes and frogs. PMID- 1748737 TI - Identity of cells produced by two stages of cytogenesis in the postnatal cat retina. AB - Cytogenesis in the postnatal cat retina was studied with the aid of 3H-thymidine autoradiography to identify the cell classes generated. Cells proliferate in two stages, which are separate spatially and temporally. Previous studies have shown that during Stage 1, cytogenesis occurs at high density at the ventricular surface of the retina, whereas Stage 2 occurs at low density in the inner retinal layers. At the ages studied, the progeny of Stage 1 cytogenesis are distributed in an annulus toward the margin of the retina, and those of Stage 2 occur central to the annulus, indicating that Stage 2 follows Stage 1. Cell genesis in Stage 1 appears to cease by P16; genesis in Stage 2 persists until between P21 and P30. The same cell classes (amacrine cells, bipolar cells, Muller cells, and rod photoreceptors) are generated during both Stages 1 and 2, but there are significant changes in their proportions both within and between stages. The proportion of the Stage 1 mitoses that form bipolar cells increases from 31% at P0 to 62% at P14. A corresponding decrease is observed in the proportion of rods (from 60% at P0 to 32% at P14). The proportion of cells generated during Stage 2 that become rods increases from 39% at P0 to 70% at P21, whereas the proportion of bipolar cells decreases from 50% at P0 to 23% at P21. Muller cells form a relatively constant proportion (8 to 15%) of the cells generated during both Stage 1 and 2. Thus at the end of Stage 1, mostly bipolar cells are generated; at the end of Stage 2, mostly rods are generated. PMID- 1748738 TI - Somatotopic component of the multisensory map in the deep laminae of the cat superior colliculus. AB - The topographic organization of the somatosensory representation in the deep layers of the cat superior colliculus was reexamined using methods previously used to examine the visuotopy in these layers. This technique identified the distribution of neurons in the superior colliculus that represent a designated region of the body surface (i.e., a dermal image), as well as assessed the differential distribution of deep layer neurons representing different body regions (e.g., face, forelimb, hindlimb, etc.). When the area of densest representation within a dermal image was considered, a well-ordered somatotopy was evident that was similar to the one previously described (Stein et al., '76: J. Neurophysiol. 39:401-419). Each region of the body surface, however, was represented within a surprisingly broad area of the deep layers, which often had considerable overlap with the representations of adjacent body regions. This organization was similar to that of the deep layer visuotopy and emphasizes that the representation of a peripheral stimulus is accomplished by the simultaneous activation of a large population of deep layer neurons. Furthermore, an examination of the convergence patterns on somatosensory-responsive neurons demonstrated that the somatotopy was formed primarily by multisensory neurons. These data indicate that the somatosensory representation is best considered as a component of a comprehensive multisensory functional unit that plays a critical role in effecting behavioral responses to a wide variety of stimuli. PMID- 1748739 TI - Patterns of connectivity in the cat sensory-motor cortex: a light and electron microscope analysis of the projection arising from area 3a. AB - Through its complex network of interconnections, each of the functionally specialized subdivisions in the cat primary somatosensory cortex may provide the motor cortex with different input and thus play a unique role in motor behavior. Areas 2 and 3a receive separate peripheral information. Cells in both regions project directly to the cat motor cortex but are thought to target different populations of neurons. In this study the morphology and distribution patterns of the area 3a projection to the motor cortex were compared to previous findings on the projection from area 2. Also, details of the projection from area 3a to area 2 were studied. Injections of Phaseolus vulgaris leucoagglutinin were made into area 3a and fixed brain tissue was processed for immunohistochemical staining of this anterograde tracer. Tissue was examined with the light microscope to determine the patterns of the 3a projections to area 2 and motor cortex, area 4. Axons arising from cells in area 3a terminated in multiple column-like clusters in both motor cortex and area 2. The small number of cells labeled at the injection sites suggested that multiple foci of the 3a fibers are formed by collateral axonal branches of the same neurons. The topography of the projection from area 3a to the motor cortex was more clearly defined than that from area 3a to area 2. Electron microscope analysis determined the laminar distribution and types of synapses formed between area 3a efferents and their target neurons. A high proportion of synapses was found in layer III in both target regions. However, unlike in area 4, labeled terminals were sparse in laminae I and II of area 2. Axospinous synapses were slightly more numerous than axodendritic synapses, but both were distributed similarly throughout the thickness of the cortex. In area 2 the axospinous synapses accounted for 63% of synapses and in area 4 for 57% of synapses. No axosomatic synapses were detected. PMID- 1748740 TI - The visually related posterior pretectal nucleus in the non-percomorph teleost Osteoglossum bicirrhosum projects to the hypothalamus: a DiI study. AB - This study was done to elucidate the ancestral (plesiomorphic) condition for visual pathways to the hypothalamus in teleost fishes. Three patterns of pretectal organization can be discerned morphologically and histochemically in teleosts. Their taxonomic distribution suggests that the intermediately complex pattern (seen in most teleost groups) is ancestral to both the elaborate pattern (seen in percomorphs) and the simple pattern (seen in cyprinids). The pretectal nuclei involved can be demonstrated with acetylcholinesterase histochemistry selectively and reliably in different species of teleosts, suggesting that the same-named nuclei are homologous in representatives of the three different patterns. Whereas there are visual pathways to the hypothalamus in both the elaborate (percomorph) and the simple (cyprinid) patterns, different pretectal and hypothalamic nuclei are involved. Thus visual hypothalamic pathways in these two patterns would not appear to be homologous. In this study, circuitry within the third, i.e., the intermediately complex, pattern is investigated. It is demonstrated that visual pathways project via the pretectum to the hypothalamus in Osteoglossum bicirrhosum and that they are very similar to the visual pathways in the elaborate pattern. This suggests that the circuitry in the intermediately complex pattern, as represented by Osteoglossum, is plesiomorphic (evolutionarily primitive) and the circuitry in both the simple pattern (seen in cyprinids) and the elaborate pattern (seen in percomorphs) is apomorphic (evolutionarily derived) for teleosts. PMID- 1748741 TI - PNS-CNS transitional zone of the first cranial nerve. AB - This study examined the ultrastructure of the region of transition where fascicles of olfactory axons leave the peripheral nervous system (PNS) to enter the central nervous system (CNS), the so-called PNS-CNS transitional zone. Adult rats were transcardially perfused with a solution of 1% glutaraldehyde and 1% paraformaldehyde, decapitated, and the heads decalcified over a period of several weeks in a solution of 1% glutaraldehyde in 0.1 M tetrasodium ethylenediamine tetraacetic acid; the latter solution was changed daily. It was found that astrocytes did not form the glia limitans at the nerve entry zone, unlike the situation that exists in other cranial and spinal nerves. Rather, the glia limitans in this region of the olfactory bulb was formed by a special type of glial cell, referred to as an ensheathing cell. Ensheathing cells are found only in the nerve fiber layer of the olfactory bulb. They possess a mixture of Schwann cell and astrocytic features and are more likely to be of placodal than of CNS origin. The meningeal coverings of the olfactory nerve rootlets and of the olfactory bulb are also described and the functional implications of the findings discussed. PMID- 1748742 TI - Funicular organization of avian brainstem-spinal projections. AB - The purpose of this study was to determine which reticulospinal projections need to be preserved to allow voluntary walking and to differentiate between those pathways descending within the ventrolateral funiculus versus the ventromedial funiculus. Retrogradely transported tracers (True Blue, Fast Blue, Diamidino Yellow dihydrochloride, fluorescein-conjugated dextran-amines) were used alone as discrete funicular injections (4-5 microliters) into the lumbar cord (L1), or in conjunction with a more rostral subtotal lesion of the low thoracic cord, to determine the trajectories of brainstem-spinal projections in adult ducks and geese. No difference was found between the species. The major components of the ventromedial funiculus include projections from the medullary reticular formation, pontine reticular formation, raphe obscurus and pallidus, lateral vestibular nucleus, and interstitial nucleus, and to a minor extent from the locus coeruleus, lateral hypothalamus, and nucleus periventricularis hypothalami. The components of the ventrolateral funiculus (VLF) include projections from the nucleus of the solitary tract, nucleus alatus, pontomedullary reticular formation, raphe pallidus, raphe magnus, locus coeruleus, subcoeruleus, lateral vestibular, and descending vestibular nuclei. The principal descending projections within the dorsolateral funiculus (DLF) arose from the red nucleus, the paraventricular nucleus, locus coeruleus, subcoeruleus, dorsal division of the caudal medullary reticular formation, and raphe magnus. The functional implications of the distribution of these descending pathways are discussed with regard to locomotion. Since birds were able to walk despite bilateral lesion of the DLF or VMF but were unable to walk following a bilateral lesion of the VLF, this suggests that medullary reticulospinal pathways coursing within the VLF are essential for the provision of locomotor drive. PMID- 1748743 TI - A biomechanical evaluation of a cannulated compressive screw for use in fractures of the scaphoid. AB - The compressive force generated by a 3.5 mm ASIF cannulated cancellous screw with a 5 mm head was compared with that generated by a standard 3.5 mm ASIF screw (6 mm head), a 2.7 mm ASIF screw (5 mm head), and a Herbert screw. The screws were evaluated in the laboratory with the use of a custom-designed load washer (transducer) to the maximum compressive force generated by each screw until failure, either by thread stripping or by head migration into the specimen. Testing was done on paired cadaver scaphoids. To minimize the variability that occurs with human bone, and because of the cost and difficulty of obtaining human tissue specimens, a study was also done on polyurethane foam simulated bones. The 3.5 cannulated screw generated greater compressive forces than the Herbert screw but less compression than the 2.7 mm and 3.5 mm ASIF cortical screws. The 3.5 mm cannulated screw offers more rigid internal fixation for scaphoid fractures than the Herbert screw and gives the added advantage of placement over a guide wire. PMID- 1748744 TI - Augmented external fixation of unstable distal radius fractures. AB - The technique of "augmentation" of external fixation employs the use of percutaneous Kirschner wires to secure the radial styloid fragment as a lateral buttress, elevate and fix in place the depressed lunate fossa fragment, and, when necessary, add support to the elevated articular surface by means of subarticular bone grafting. A series of 51 cases of comminuted, unstable intraarticular distal radius fractures has been managed using this technique. Detailed evaluation has demonstrated precise articular reconstitution with an overall satisfactory result rate of 92%. PMID- 1748745 TI - Malunited Colles' fractures: correction with a biplanar closing wedge osteotomy. AB - A malunited Colles' fracture causes distortion of three anatomic features of the distal radius: length of the bone and the angles of its articular surface in both frontal and sagittal planes. The relative importance of each of these factors was studied in a series of 14 patients with malunited Colles' fractures and severe disabilities. Reversal of the normal palmar tilt of the distal radius in the sagittal plane was the most consistent and serious deformity of the bone, and in five patients it was associated with dorsal subluxation of the entire carpus. Correction of the malunion was achieved with a biplanar closing wedge osteotomy without a bone graft. Resection of the ulna head and decompression of the median nerve within the carpal tunnel were done to reduce the likelihood that additional surgery would be required in the future. PMID- 1748746 TI - Classification system for factitious syndromes in the hand with implications for treatment. AB - We evaluated 29 patients with factitious disorders in the hand who received Worker's Compensation benefits. Three types of factitious hand disorders based on physical presentation were self-mutilation and wound manipulation, edema, and finger and hand deformities. Two distinct psychological diagnoses present were factitious disorder with physical symptoms and conversion disorder. The Minnesota Multiphasic Personality Inventory revealed two personality profiles: emotionally dependent and angry and hostile. Behavioral treatment was implemented. The emotionally dependent group responded well, with 80% returning to work. The angry and hostile group had a much poorer response, with 21% returning to work. None of the self-multilating patients returned to work. We recommend a combined evaluation by a physician, a psychologist, and a hand therapist to achieve a definitive diagnosis for these disorders. The identification of psychological profiles assists in ascertaining which patients will be responsive to behavioral treatment. PMID- 1748747 TI - Glove perforation in hand surgery. AB - A survey of glove perforation in 100 consecutive hand surgery operations was undertaken. A total of 397 pairs of gloves were tested for punctures after the operation. Evidence of perforation was found in 19% of the gloves used, and only in 12 cases did the surgeons actually realize that a perforation had occurred. With a perforation rate of 43%, the surgeons were significantly more at risk of glove perforation than the other members of the operating team. PMID- 1748748 TI - The measurement of cold sensitivity of the hand. AB - There is no widely accepted method of measuring the severity of cold sensitivity of the hand. A patient-answered questionnaire was developed. This consisted of seven items divided into two subscales: the first to measure the severity of cold sensitivity, and the second to grade exposure of the hands to cold at the workplace. The test-retest reliability was 0.92 for the severity subscale and 0.94 for the work exposure scale. An initial test of validity supports the use of the scale to measure cold sensitivity of the hand. PMID- 1748749 TI - Effects of cold exposure on the circulation of replanted fingers during the early postoperative period. AB - The replanted finger after a complete amputation is an excellent model for the study of many aspects of vascular physiology. In the present clinical study, 10 patients were investigated to evaluate the incidence of cold-induced vasospasm in replanted digits during the early postoperative period. The results indicate that cold-induced vasospasm is not a risk factor in the early postoperative phase after digital-replantation surgery. It is concluded that cold-induced spasm of the digital arteries is primarily a central, nerve-mediated reflex. PMID- 1748750 TI - Pseudotumor of the palm due to an anomalous flexor digitorum superficialis muscle belly. AB - A pseudotumor of the palm was due to an anomalous flexor digitorum superficialis muscle belly. Magnetic resonance imaging is an excellent diagnostic tool to define the three dimensional extension of such an anomaly. Surgical resection of the anomalous muscle belly resulted in a complete relief of all symptoms. PMID- 1748751 TI - Locked thumb metacarpophalangeal joint caused by sesamoid entrapment. AB - We report an unusual case of locked thumb in a 24-year-old man, caused by entrapment of the radial sesamoid in the metacarpophalangeal joint. Tomography clearly revealed sesamoid entrapment in the joint. Surgical exploration and cadaver dissection demonstrated that avulsion of the proximal portion of the palmar plate and some dissociation of the sesamoid from the palmar plate with intraarticular displacement were necessary for the sesamoid to be trapped in the joint. PMID- 1748752 TI - Comparison of four objective methods of monitoring digital venous congestion. AB - This study sought to determine which of the four most commonly used objective monitoring modalities--pulse oximetry, laser Doppler flowmetry, skin surface temperature measurement, and skin surface fluorescence--is best able to detect early digital venous congestion. Digital venous congestion was induced in 12 hands by inflating a digital cuff to 5 mm Hg above the resting diastolic pressure. The cuff remained inflated for 1 hour while monitoring was done at 10 minute intervals. The baseline and experimental laser Doppler indices differed by at least 30% in each subject, and the laser Doppler index was always less than 40% during venous congestion. Skin surface fluorescence gave falsely normal results in three of eight hands, while pulse oximetry failed to detect venous congestion in any hand. The difference in temperature between the control and experimental fingers almost always exceeded the threshold of 2.5 degrees C. The results indicate that both laser Doppler flowmetry and skin surface temperature measurement are highly accurate methods of monitoring early digital venous congestion that are noninvasive and easy to use. Skin surface temperature measurement has further advantages in that thermometers are less expensive and easier to transport than laser Doppler devices. In contrast, skin surface fluorescence is invasive and cumbersome in addition to being less sensitive to experimentally induced early digital venous congestion than either laser Doppler flowmetry or skin surface temperature measurement. Pulse oximetry is unreliable in detecting early digital venous congestion. PMID- 1748753 TI - Venous anatomy of the thumb. AB - The venous anatomy of 20 thumbs (10 pairs) was detailed by latex injection. The thumbs were studied on the dorsal, palmar, radial, and ulnar surfaces. Characteristic patterns were found; these included a dominant longitudinal network, palmar veins within the pulp, oblique veins at the interphalangeal joint on the radial side, and a web space vein. A layered vascular pattern with a superficial fine network overlying a deeper system was noted. Cross sections were taken at the metacarpophalangeal joint and at the proximal and distal phalanges. The distribution of the vessels in cross section reveals consistent dorsal veins at all levels, as well as palmar veins distal to the interphalangeal joint in all thumbs. Palmar veins were present over the length of the proximal phalanx in more than 65% of the thumbs. PMID- 1748754 TI - Acute and chronic ischemia of the hand: pathophysiology, treatment, and prognosis. AB - Fifty consecutive patients with acute and chronic ischemia of the hand were investigated by Allen testing, Doppler ultrasound, digital plethysmography, and angiography over a 4-year period. The pathophysiologic mechanism responsible for the ischemia was determined to be emboli in 6%, vasospasm in 10%, thrombosis or "sludging" in 28%, occlusive disease in 26%, and occlusive disease associated with either vasospasm or external compression in 30%. Ten patients required emergency medical treatment with intraarterial streptokinase, intravenous heparin, or dextran 40 and continuous stellate ganglion blocks, and three patients required emergency microsurgical revascularization because of radial artery thrombosis. Patients with chronic ischemia of the hand were maintained on nifedipine, 30 to 60 mg daily, and pentoxifylline, 1200 mg daily. Seven patients underwent digital sympathectomy and 14 patients underwent microsurgical revascularization as prophylactic procedures for chronic digital ischemia. Amputations were required in 18 patients because of end-stage gangrene. Long-term follow-up revealed a 20% incidence of recurrent digital ulcerations. There have been six deaths during follow-up, five of them due to myocardial infarction; this reflects the underlying systemic arteriopathy in many of these patients. PMID- 1748755 TI - Histologic anatomy of the triangular fibrocartilage. AB - The collagen arrangement of the triangular fibrocartilage complex was studied in 20 fresh cadaver wrists by means of standard and polarized light microscopy and scanning electron microscopy. The collagen fibres in the articular disk are arranged in undulating sheets oriented at oblique angles to each other. The fibers of the radioulnar ligaments are oriented longitudinally from the radial origin to the ulnar insertion. The origin of the articular disk from the radius is characterized by thick fibers 1 to 2 mm in length radiating from the radius into the articular disk. Five specimens were also injected with india ink. The radioulnar ligaments and the peripheral 15% to 20% of the articular disk are well vascularized, whereas the central 80% of the articular disk is avascular. PMID- 1748756 TI - The microvasculature of the triangular fibrocartilage complex: its clinical significance. AB - The microvascular anatomy of the triangular fibrocartilage complex was investigated in 10 cadaver specimens by histology and tissue clearing (Spalteholz) techniques. It was found that the triangular fibrocartilage of the wrist is supplied by small vessels that penetrate the triangular fibrocartilage complex in a radial fashion from the palmar, ulnar, and dorsal attachments of the joint capsule and supply the peripheral 10% to 40%. The inner (horizontal) portion is avascular, and no vessels cross the radial attachment of the triangular fibrocartilage complex. The results of this study suggest that tears in the periphery of the triangular fibrocartilage complex may have sufficient blood supply to mount a reparative response and, in theory, can be repaired. However, tears that occur in the center and along the radial attachment do not have immediate access to a blood supply and are not likely to heal. PMID- 1748757 TI - The distal radioulnar ligaments: a biomechanical study. AB - The mechanical roles of the triangular fibrocartilage have been examined in three experiments. Kinematic analysis by a stereophotogrammetric method revealed that the palmar radioulnar ligament was taut in supination and that the dorsal radioulnar ligament was taut in pronation. In full pronation, the palmar radioulnar ligament decreased to an average of 71% of its length in tension. In full supination, the dorsal radioulnar ligament decreased to an average of 90% of its length. Mechanical testing of the triangular fibrocartilage under axial load disclosed a significant laxity (mean: 10.4 mm), which was decreased in pronation. Transverse loading tests demonstrated that the triangular fibrocartilage is less stiff in neutral forearm rotation. Study of the material properties of the palmar and dorsal parts of the triangular fibrocartilage showed these structures to be strong ligaments with material properties similar to those of the radiocarpal ligaments. PMID- 1748758 TI - Distal ulnar head shortening for treatment of triangular fibrocartilage complex tears with ulna positive variance. AB - Patients with a tear of the horizontal part of the triangular fibrocartilage complex and ulna plus variance were treated by excision of the distal part of the ulnar head. Three of the seven consecutive patients also had lunotriquetral ligament injuries and had fusions of that joint. Six of the seven patients had either complete relief or marked improvement of symptoms at the distal radioulnar joint. When ulnar shortening is indicated, ulnar head shortening should be considered. PMID- 1748759 TI - Hemiresection-interposition arthroplasty of the distal radioulnar joint associated with repair of triangular fibrocartilage complex lesions. AB - Sixteen wrists of 15 patients with traumatic triangular fibrocartilage complex tears were treated by hemiresection-interposition arthroplasty of the distal radioulnar joint combined with repair of the torn triangular fibrocartilage complex. The surgical procedure was performed to avoid impingement of the ulnar head against the reconstructed triangular fibrocartilage complex. Most of the wrists showed a positive ulnar variance. The average age of the patients was 39 years. Follow-up averaged 41 months. Complete relief of pain was obtained in 10 wrists. Slight pain persisted in 6 wrists, although it was less than before surgery. The range of motion of the wrist joint and forearm improved postoperatively. Grip strength in all wrists increased. Postoperative complications occurred in 7 wrists of 6 patients: reoperation in 2 wrists, fracture in 1, and tendinitis of the extensor carpi ulnaris in 4. All 15 patients subsequently returned to their previous occupations. PMID- 1748760 TI - The Sauve-Kapandji procedure: a salvage operation for the distal radioulnar joint. AB - The Sauve-Kapandji procedure, a distal radioulnar arthrodesis with surgical creation of a pseudoarthrosis in the distal ulna, was used to treat 11 patients. Although all patients had had at least one previous operation on the involved wrist, they were still having pain and functional limitations. Ten patients were available for follow-up, which averaged 33 months. Of the nine patients with posttraumatic arthritis, six had excellent results (a painless wrist that averaged 82 degrees of pronation and 83 degrees of supination). Three patients had good results (mild pain during activities with an identical range of forearm rotation). One patient who had rheumatoid arthritis had an excellent result for 3 years but recently had a radiocarpal wrist fusion because of radiocarpal arthritis. We have found the Sauve-Kapandji procedure to be a reliable treatment option for intractable disorders of the distal radioulnar joint and recommend it as a salvage procedure when previous treatment has failed. PMID- 1748761 TI - Extensor mechanism of the fingers. I. A quantitative geometric study. AB - A close-range stereophotogrammetric measurement system was used to determine the three-dimensional geometric characteristics of the extensor assembly in seven human finger specimens and five finger configurations. The numerical data obtained showed that, although changes in length of the different bundles are small, their spatial orientation varies considerably from one to another position. This information should help to improve the accuracy of models derived to understand the extensor assembly behavior in normal and pathological conditions. PMID- 1748762 TI - Extensor mechanism of the fingers. II. Tensile properties of components. AB - Seven fresh human finger specimens have been studied to determine the differences in structural stiffness between different components of the extensor assembly. Differences were found to be significant, ranging from an average of 275 N/mm for the proximal and distal segments of the central band to an average of 40 N/mm for the central-to-lateral intercrossing fascicles. The terminal tendon of the lateral band was shown to be as stiff as the middle segment of the central band. PMID- 1748763 TI - The extensor medii proprius and anomalous extensor tendons to the long finger. AB - The extensor medii proprius is a muscle analogous to the extensor indicis proprius in that it has a similar origin, but inserts into the long finger. The extensor indicis et medii communis muscle is an extensor indicis proprius muscle that splits to insert into both the index and long fingers. The extensor tendons to the fingers were dissected in 58 adult hands to determine the incidence and anatomy of the extensor medii proprius and extensor indicis et medii communis. The incidence of the extensor medii proprius was 10.3% and the incidence of the extensor indicis et medii communis was 3.4% in this series. The extensor medii proprius and extensor indicis proprius muscles had a common origin in all cases. The insertion of the extensor medii proprius into the dorsal aponeurosis was palmar and ulnar to the extensor digitorum communis of the long finger, but in one case, the extensor medii proprius inserted into the deep fibrous tissue proximal to the metacarpophalangeal joint. The tendon slip of the extensor indicis et medii communis inserting into the long finger did not insert into the dorsal aponeurosis, but into the deep fibrous tissue near the metacarpophalangeal joint. Both the extensor medii proprius and the extensor indicis et medii communis may represent evolutionary remnants. Awareness of their potential presence and anatomy should be helpful in extensor identification, repair, and transfer. PMID- 1748764 TI - Results of acute zone III extensor tendon injuries treated with dynamic extension splinting. AB - Motivated by the favorable results of dynamic splinting in the treatment of more proximal extensor tendon injuries, we explored the use of dynamic splinting in the treatment of zone III extensor tendon lacerations. Twenty-two tendon repairs in 19 patients were available for review. On the basis of degree of extension lag and pulp-to-palm distance, 14 repairs were rated as excellent, 6 as good, and 2 as fair. Using total active motion at 10 weeks, the proximal interphalangeal and distal interphalangeal joints averaged 170 degrees. There was one mild boutonniere deformity. The results of this prospective study show that carefully monitored dynamic splinting is safe in the treatment of zone III lacerations. When results were compared with the results of our method of static splinting used prior to this prospective study, patients returned to full activities with good-to-excellent results 8 weeks earlier instead of at 16 to 18 weeks. PMID- 1748765 TI - "Temporary ectopic implantation". PMID- 1748766 TI - Successful reeducation of functional sensibility after median nerve repair at the wrist. PMID- 1748767 TI - Osteoarthritis of the trapeziometacarpal joint: the pathophysiology of articular cartilage degeneration. I. Anatomy and pathology of the aging joint. AB - An anatomic study of the trapeziometacarpal joint was conducted on 47 cadaver thumb specimens. The superficial capsule restrained only metacarpal rotation about its long axis. Intracapsular anatomy was notable for a large anterior subthenar recess limited dorsally by the abductor pollicis longus insertion and palmarly by the deep palmar or "beak" ligament. This beak ligament was essential for translational stability of the metacarpal on the trapezium with flexion of the thumb ray. There was a direct correlation between the status of the articular surfaces and the integrity of the beak ligament. Normal surfaces were associated with an intact ligament confluent with the hyaline cartilage of the palmar lip of the metacarpal; degeneration of the palmar lip cartilage was always associated with attritional detachment of the beak ligament. Advanced articular disease occurred only in the palmar contact areas and was predicted by degeneration of the adjacent beak ligament; only nonprogressive chondromalacia was found on the dorsal portions of the articular surfaces. PMID- 1748768 TI - Osteoarthritis of the trapeziometacarpal joint: the pathophysiology of articular cartilage degeneration. II. Articular wear patterns in the osteoarthritic joint. AB - An anatomic and radiographic study of the osteoarthritic trapeziometacarpal joint was conducted on 27 surgical specimens harvested during basal joint arthroplasty. Surface wear patterns were analyzed by hyaline cartilage staining, and relative involvement of trapezium and metacarpal was calculated as the trapezium/metacarpal eburnation ratio. Eburnation occurred only on facing trapeziometacarpal surfaces in contact areas of the palmar compartment. Metacarpal degeneration began at the palmar joint margin adjacent to the beak ligament and extended dorsally, while trapezial degeneration originated on the central palmar slope and spread centrifugally with more advanced disease. Eburnation consistently involved a greater surface area on the trapezium than on the metacarpal in a ratio of nearly 3:1. A decreasing trapezium/metacarpal eburnation ratio correlated closely with worsening radiographic stage. These observations suggest translation of metacarpal on trapezium in the production of arthritic surface lesions and support a hypothesis of pathologic joint instability as the cause of trapeziometacarpal osteoarthritis. PMID- 1748769 TI - Tendon suspension sling arthroplasty for thumb trapeziometacarpal arthritis. AB - Forty consecutive tendon suspension sling arthroplasties for relief of pantrapezial osteoarthritis in 38 patients were reviewed. The procedure consists of excision of the trapezium and reconstitution of the tethering action of the first intermetacarpal and the palmar oblique carpometacarpal ligaments; 50% of the distally based flexor carpi radialis tendon is used. A double figure-eight sling suspends the first metacarpal securely, followed by distal advancement of the abductor pollicis longus to tighten the sling and palmarly abduct the thumb ray. The technique resulted in relief of pain, preservation of strength, maintenance of a normally contoured first web space, and functional carpometacarpal range of motion. Procedures were performed over a 4-year period (1986 to 1990), with an average follow-up of 21 months. At final follow-up, 85% of the patients had minimal symptoms; key pinch and grip strengths measured 76% and 81% of the contralateral uninvolved side, respectively. The logic of the mechanical design of the procedure and encouraging subjective and objective follow-up at 4 years make the technique of tendon suspension sling arthroplasty an attractive alternative to existing procedures for the surgical management of recalcitrant and disabling osteoarthritis of the basilar thumb joint. PMID- 1748770 TI - Biomechanical and functional testing of plate fixation devices for proximal phalangeal fractures. AB - Functional testing in fresh cadaver digits of a dorsally applied mini-H plate, a mini-straight plate, and a laterally applied mini-condylar plate demonstrated that all three significantly reduce (p less than 0.2) simulated active PIP joint flexion. The mini-condylar plate, however, provided the least reduction of any of the three plates. Biomechanical testing of the same three plates on proximal phalanx after osteotomy in apex palmar and apex dorsal direction bending showed all three plates to provide rigidity less than the intact bone. PMID- 1748771 TI - Biomechanical comparison of cannulated small bone screws: a brief follow-up study. AB - The compressive forces generated by the ASIF and Herbert small bone cannulated screws were measured in the laboratory with the use of simulated bones and a custom-designed load washer as a means of quantifying their fixation capabilities. Comparative data were also generated for the Herbert scaphoid bone screw and the ASIF 4 mm cancellous screw. The cannulated Herbert bone screw and the ASIF 4 mm cancellous screw were found to have nearly identical compression capabilities. Both generated compression forces approximately five times those of the Herbert scaphoid bone screw. The ASIF small cannulated screw demonstrated a compressive capacity 2 1/2 times that of the Herbert screw. PMID- 1748772 TI - Society/community expectation. PMID- 1748773 TI - Role of fine needle aspiration biopsy cytology in general practice. PMID- 1748774 TI - Clinical profile of herpes zoster ophthalmicus. AB - Herpes zoster ophthalmicus was seen in 22 cases out of 195 cases of herpes zoster (11.3% incidence). It was affecting mainly adults (90.9%). Oedema over the lids (81.8%) was invariably present and lead to ptosis. Mucopurulent conjunctivitis, predominantly mucoid (72.7%) was the commonest manifestation associated with vesicles over the lid margins. Sectorial (22.7%) and diffuse (9.1%) episcleritis appeared in later part of first week, while nodular episcleritis was observed in one case only on 12th day of the disease. Nummular keratitis was seen in 31.8% of cases between 8-10 days. Iritis and iridocyclitis was seen in 45.4% of cases out of which 36.3% had secondary ocular hypertension (glaucoma). Neuroparalytic keratitis and internal ophthalmoplegia were detected in one patient each. Postherpetic neuralgia occurred in 22.7% of cases and was uncommon in younger age group (below 40 years, 4.5%). Carbamazepine was effective in relieving the herpetic pain. PMID- 1748775 TI - Carcinoma penis. AB - In the present study 90 cases of carcinoma penis were studied. The disease is more common after the age of 40 years; phimosis was found to be most important predisposing factor. Most common presentation was proliferative lesion with commonest involvement of glans penis. All the cases were of squamous cell carcinoma except one case of malignant melanoma. Clinical determination of lymph node metastasis is falacious as there was discrepancy between clinical and histopathological stage of the disease in 26.67% of cases. Therefore lymph node biopsy at the time of primary surgery is advocated. The result of total amputation is better than other mode of treatment. PMID- 1748776 TI - Postoperative analgesia with extradural buprenorphine and pentazocine. AB - A randomised study of the efficacy, duration of action and side-effects of two analgesic regimens following lower abdominal surgery is described. Patients received extradural pentazocine 30 mg or extradural buprenorphine 0.3 mg to provide postoperative analgesia. Interval for the next analgesia was significantly greater after extradural buprenorphine (18.96 hours) than after extradural pentazocine (8.39 hours) (p less than 0.001). No serious side-effects were reported. PMID- 1748777 TI - Evaluation of different surgical procedures in filarial lymphoedema of lower extremity. AB - Ninety-six cases of different stages of lymphoedema of inferior extremity were taken for study. Twenty-four patients with early lymphoedema (stage II) were subjected to lymphonodovenous shunt (LNVS) operation; 54 patients of late lymphoedema with skin changes (Stage IV) were subjected to Charles' operation and 18 patients with late lymphoedema without skin changes (stage III) were subjected either to Sistrunk's or Thompson's operation. All the results were studied, evaluated and compared. The cases subjected to LNVS operation had a rapid relief of lymphoedema in the early postoperative period followed by slow reduction. Patients subjected to Charles' operation had immediate volume and circumference reduction and take up of skin grafting was 84%. The cases subjected to Thompson's operation did not have satisfactory reduction in volume and circumference postoperatively. There were a few minor postoperative complications in all these procedure, infection being most notable in those who had undergone Charles' operation. It is concluded that while excisional surgery, such as Charles' operation becomes necessary for late stages of lymphoedema, which have progressed to elephantiasis, nodovenous shunt alone is sufficient to relieve early stages of lymphoedema due to filariasis. PMID- 1748778 TI - Dissolution of gall-stones in vitro. AB - An in vitro study on dissolution of 36 gall-stones obtained from 3 patients (12 stones from each patient) was carried out in heparin, bile salt and clofibrate solutions of different strengths. Heparin was found to be a poor solvent while bile salt (sodium desoxycholate) proved better and clofibrate the best solvent in various concentrations used. In addition 3 stones, one from each patient, were placed in normal saline to serve as control. PMID- 1748779 TI - Antibacterial susceptibility of anaerobes by agar dilution method. AB - Of the 9 antibacterials, vancomycin alone at its break-point (optimum blood level) revealed highest (93.3%) efficacy on Gram-positive cocci. The remarkable activity of carbenicillin, chloramphenicol and vancomycin on Gram-positive cocci (95.4 to 96.9%), carbenicillin and chloramphenicol on Gram-positive bacilli (94.8% to 98.2%) and chloramphenicol on Gram-negative bacilli (95.4%) was noted by increasing their concentrations 1.5 to 2.5 times above their break-points. These (and even higher) concentration, however, showed relatively lower efficacy of metronidazole, rifampicin, penicillin, clindamycin and erythromycin on Gram positive cocci (76 to 84.1%), rifampicin, tetracycline, erythromycin, clindamycin and vancomycin on Gram-positive bacilli (81 to 87.9%) and clindamycin, metronidazole, rifampicin and carbenicillin in Gram-negative bacilli (72.7 to 84%). By and large, rifampicin, chloramphenicol and carbenicillin are also quite effective (72.1 to 75.1%) at lower concentration. PMID- 1748780 TI - Spirometric indices of early airflow obstruction. AB - Thirty cigarette smokers and 25 non-smoking controls, all men were evaluated by history, physical examination and simple spirometry. The history and physical examination were not of much use in predicting airflow obstruction. Forced mid expiratory flow (FEF 25-75%) was abnormally low in 23 of the 30 subjects, while forced expiratory volume in 1 second (FEV1) and FEV1/FVC (forced vital capacity) were less sensitive. Thus simple spirometry is a useful screening tool to detect early airflow obstruction even when it is clinically undetectable. PMID- 1748781 TI - Clinical profile of trichotillomania. AB - Twenty-four cases of trichotillomania attending psychiatry outpatient department and child guidance clinic at Kalawati Saran Children's and Smt Sucheta Kriplani Hospitals over a period of 2 years from July, 1985 to November 1987 were studied. Females (66.7%) outnumbered the males (33.3%). Majority of cases belonged to age group 6-10 years (54.2%) and nuclear family (68.5%). Nail-biting (25.0%) was the commonest associated neurotic trait, followed by enuresis (20.9%), temper-tantrum (12.5%), etc. A past history of hysterical fits and neurotic depression was found in 3 cases (12.5%) and 2 cases (8.3%) respectively. Family history of neurosis was seen in mothers and fathers of 20.9% and 12.5% cases respectively. Trichobezoars and trichophytobezoars were found in 6 cases (25.0%) and 3 cases (12.5%) respectively. Majority of patients of trichobezoars presented with vague complaints like heaviness in the stomach (55.6%), inability to gain weight (44.4%), etc, while 22.2% cases were asymptomatic and detected only on screening. PMID- 1748782 TI - An unusual case of eventration of the diaphragm with intractable vomiting. PMID- 1748783 TI - Sports injuries in common rural games and their management. PMID- 1748784 TI - Pathogenesis of dengue haemorrhagic fever. PMID- 1748785 TI - Relief of chronic pain. PMID- 1748786 TI - Platelet adhesiveness in diabetes mellitus with relation to treatment. AB - To determine whether diabetes mellitus alters the function of platelets, a study on platelet adhesiveness in 30 controls and 75 newly diagnosed diabetics (25 cases of type-1 and 50 cases of type-II) before and after treatment was undertaken. The platelet adhesiveness was 68.83 +/- 6.09% (mean + SD) in type-I diabetics, 72.43 +/- 6.10% in type-II diabetics and 56.31 +/- 9.62% in controls (p less than 0.001 for all comparisons). In complicated diabetics (54 cases) the platelet adhesiveness was 72.33 +/- 5.99% and in uncomplicated diabetics (21 cases) it was 67.33 +/- 5.82% (p less than 0.05). Platelet adhesiveness was significantly reduced after treatment (with insulin it was 62.12 +/- 7.46%, with phenformin 62.10 +/- 8.63 and with tolbutamide 67.12 +/- 7.97%) when compared with pretreatment values. Platelet adhesiveness had no significant correlation with blood sugar and serum cholesterol levels. These results support the concept that platelet adhesiveness is high in diabetes mellitus and is reduced with control of diabetic state after treatment. PMID- 1748787 TI - Non-operative treatment of fractures of the humeral shaft: a comparative study. AB - Forty cases of diaphyseal fracture of humerus were treated by functional cast bracing (FCB). Results were compared with a series of 25 patients treated by U cast method. Average time taken for union was 7.5 weeks with a range of 5-14 weeks by FCB method. Fractures treated by U cast method took on an average 10 weeks to unite. Stiffness at shoulder and elbow was uniformly found in patients treated by U cast. More than 50% patients had varus angulation less than 5 degrees after treatment by FCB. Only 16% had varus angulation less than 5 degrees by U cast method while 32% had varus angulation more than 15 degrees. FCB is distinctly superior method of treatment for diaphyseal fracture of humerus. PMID- 1748788 TI - A study of prolonged labour. AB - Two hundred and three consecutive cases of prolonged labour have been retrospectively reviewed from January 1984 to December 1986. The incidence of prolonged labour was 4.39%. It was noted that 66.5% of the patients with prolonged labour were unbooked emergency admissions, and 73.3% were primipara. The causes of prolonged labour were the occipitoposterior position (10.8%), relative cephalopelvie disproportion (18.2%), uterine dysfunction (44.5%), and in 26.1% an obstructive cause was present. A spontaneous vaginal delivery occurred in 34.4%, a forceps delivery in 22.6% and the caesarean section rate was 29%. The maternal mortality, febrile and non-febrile morbidity were 9.7 per 1000 total births, 42.8% and 17.2% respectively, which showed a direct relation to the duration of labour, and a significant increase in the patients with obstructed labour, and after an abdominal delivery. The corrected perinatal mortality was 165 per 1000 total births, which was also directly related to the duration of labour, and 74.3% of the perinatal deaths occurred in the patients with obstructed labour. The perinatal mortality in the study group was nearly three times higher than the overall hospital group. Neonatal morbidity occurred in 48.8% of the newborns. PMID- 1748789 TI - Electrocardiographic changes in tetanus: a serial study. AB - Serial electrocardiograms (ECGs) were recorded in 20 consecutive male patients admitted to the Infectious Diseases Hospital, Calcutta with generalised tetanus. Age of patients varied from 5 to 40 years (mean age 20.4 years). Ten patients died. ECGs were recorded daily for the first week after admission and later every 2nd or 3rd day. Altogether, 167 ECGs were analysed. Sinus tachycardia was present in 17 (85%) patients, prolonged QT interval in 12 (60%) patients, non-specific ST T abnormalities in 12 (60%) patients and P wave changes in 10 (50%) patients. Other abnormalities recorded, included short PR interval, supraventricular tachycardia, intraventricular conduction delay, sinus bradycardia, 1 degree A-V block, abnormal axis deviation, right ventricular hypertrophy and sino-atrial Wenckebach phenomenon, although all of the findings cannot clearly be attributed to tetanus. Spatial QRS-T angle was calculated in 18 of these patients to determine any possible change in this parameter of prognostic significance. Two out of 9 who survived had abnormally wide (greater than or equal to 55 degrees) spatial QRS-T angle on admission; the angle narrowed with recovery. In the non survivor group, 4 patients had abnormally wide QRS-T angles on admission; further widening was noted in patients on whom follow-up tracings were available. The difference in spatial QRS-T angle between the survivor and the non-survivor groups was statistically significant (p less than 0.05). Spatial QRS-T angle changes have not been reported in tetanus before. Although non-specific, serial study in individual cases would be useful in assessing prognosis. PMID- 1748791 TI - Vertebral artery injury: management by packing. PMID- 1748790 TI - Study of immunisation: knowledge, attitude and practice. AB - A study was conducted to find out the knowledge, attitude and practice of preventive health care among the industrial workers by interviewing the workers of Durgapur Steel Plant, Durgapur and their family members who attended the health unit. The study revealed that 7.98% of the industrial workers were not aware of preventive aspects of health care. Most of this group were illiterate, rural in origin with family income less than Rs 1000 per month. Female child and the third and fourth child were more neglected. Main source of knowledge about preventive health care is mass media. Trade unions did not play any role in health education. There is seasonal variations in number of immunisation and drop out. Most common reason for drop out was negligency on the part of the parent and the parents remaining out of station. About 1% of the workers believed in other than scientific system of medicine. PMID- 1748792 TI - Spontaneous rupture of a gravid uterus resulting in abdominal pregnancy and lithokelyphos formation. PMID- 1748793 TI - An unusual case of primary renal cell carcinoma with normal excretory urography, sonography and computed tomography. PMID- 1748794 TI - Pyoderma. PMID- 1748795 TI - Who is afraid of cancer? PMID- 1748796 TI - Aspirin and coronary artery disease. PMID- 1748797 TI - Chemo-immunotherapy and immunological study in carcinoma of larynx and laryngopharynx. AB - Eighteen of 25 patients had squamous cell carcinoma in the supraglottic region. Anergy to skin test antigen (DNCB) and T-cell mitogen (PHA) was observed in 17 patients with laryngeal and laryngopharyngeal malignancies. Chemo-immunotherapy did not improve the skin reactivity to either agents. However, a rise in absolute T-cell counts was observed following combined therapy. Moreover, T-lymphopenia was detected in the patient group prior to therapy as compared to mean T-cell counts in normal control subjects. PMID- 1748798 TI - A profile of pyogenic meningitis in children. AB - Clinical profile of pyogenic meningitis was studied in 256 cases over a period of 8 years. The male to female ratio was 1.46: 1 and 83.6% of the patients were less than 3 years of age. Fever, altered sensorium, refusal to feed, convulsions and vomiting were the common presenting symptoms. Six (2.3%) of them had subnormal temperature and the sensorium was normal in 12.5% of cases. Cerebrospinal fluid was clear in 9.4%, cell count was less than 100/cmm in 8.2%, sugar was more than 40 mg% in 24.2% and protein was less than 50 mg% in 12.5% of cases. Diplococcus pneumoniae was the commonest causative agent. The overall mortality was 30.5%. It is concluded that young children suffering from this disease may not have the typical features and one should have the highest suspicion to make an early diagnosis so that the morbidity and mortality from this condition can be reduced. PMID- 1748799 TI - Effect of simultaneous isoniazid administration on pharmacokinetic parameters of pyrazinamide. AB - Pyrazinamide (PZN) was administered to 10 patients of pulmonary tuberculosis (for 7 consecutive days) each day after an overnight fast. On 8th day serum levels and urinary elimination were measured at 2,4,6 and 8 hours. Simultaneous administration of isoniazid to same patients significantly decreased the peak serum concentration (Cmax). Although, time to peak serum concentration (Tmax) remained unaffected, serum half life (t1/2) prolonged, the elimination rate constant (Kel) and area under serum concentration time curve (AUC) decreased and apparent volume of distribution (Vd) and plasma clearance (Clp) of PZN increased significantly. However, the cumulative per cent dose of PZN excreted in urine was not changed significantly. Although, serum levels of PZN were decreased at 2, 4, 6, and 8 hours, PZN levels remained above minimum effective concentration thereby not affecting the therapeutic status of PZN administered in combination with isoniazid, if PZN is administered in moderate doses. PMID- 1748800 TI - Cardiovascular responses to cold pressor test: a test for autonomic functions. AB - Circulatory dynamics during the cold pressor test, done by immersing the hand in water at 5 degrees C for one minute, were studied in 30 male healthy volunteers. All the subjects responded to the test with statistically significant increase in blood pressure (22.04%, p less than 0.001), heart rate (11.21%, p less than 0.001), galvanic skin resistance (36.17%, p less than 0.001) and decrease in forearm blood flow (40.85%, P less than 0.001). The measurement of cardiovascular responses following cold pressor test constitutes another test which can be used to test the efficiency of the autonomic nervous system in various autonomic neuropathies. PMID- 1748801 TI - Sublingual nifedipine in hypertensive emergencies with special reference to cerebrovascular accident. AB - Effect of sublingual nifedipine was evaluated in 39 cases of hypertensive emergencies (diastolic blood pressure greater than or equal to 120 mm Hg with impending organ failure, loss of vital function or death). It was found to be effective (95%), safe, with prompt (with 15 minutes) and predictable response (lowering of systolic blood pressure, diastolic blood pressure, mean arterial pressure by 30% at the end of 3 hours), and few adverse effects. Its use in patients of cerebrovascular accident (24 cases) was found to be effective and safe without any significant clinical problem or increased mortality. PMID- 1748802 TI - Doubting atopy? AB - Sera of 37 patients attending the allergic clinic and of 10 normal healthy non allergic controls were collected and in a double blind manner they were tested using phadiatop RIA for differentiation of patient's symptoms as due to atopy or otherwise without performing other troublesome investigations. It is an easy, less time consuming and reliable technique. PMID- 1748803 TI - Multiple intervertebral disc prolapse. PMID- 1748804 TI - Mismatched transfusion without any untoward side-effect. PMID- 1748805 TI - Peptic ulcer--newer concepts. PMID- 1748806 TI - Dripless cholecystectomy. PMID- 1748807 TI - A new clinical test in gastroduodenal perforation. PMID- 1748808 TI - Febrile convulsion. PMID- 1748809 TI - Quantitation of plasma levels of 8-methoxypsoralen by competitive enzyme-linked immunosorbent assay. AB - An immunologic method for the quantitation of 8-methoxypsoralen (8-MOP) levels in human plasma has been developed. A monoclonal antibody recognizing 8-MOP was prepared by immunizing mice with an 8-MOP derivative conjugated to bovine serum albumin with 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide-HCl. The antibody was characterized by competitive enzyme-linked immunosorbent assay (ELISA) and recognizes 8-MOP (50% inhibition at 2 pmol) as well as structurally related psoralen derivatives including 4'-aminomethyl-4,5',8-trimethylpsoralen (50% inhibition at 50 pmol), 5-methoxypsoralen (50% inhibition at 150 pmole), and 6,4,4'-trimethylangelicin (50% inhibition at 360 pmol). The assay has a limit of sensitivity of 1 ng/ml plasma. For analysis of 8-MOP levels in plasma, samples were first extracted using SepPak C18 cartridges. The extracts were analyzed for 8-MOP levels both by ELISA and high-pressure liquid chromatography. There was a good correlation between the values determined by both methods (r = 0.92, p less than 0.0005). The development of immunologic methods should greatly facilitate the quantitation of 8-MOP levels in patient plasma. PMID- 1748810 TI - Structural investigations of human stratum corneum by small-angle X-ray scattering. AB - The structure of human stratum corneum was investigated with small-angle X-ray scattering (SAXS). At room temperature the scattering curve was characterized by a strong intensity at low scattering vector (Q less than 0.8 nm-1) and two complicated diffraction peaks originating from a lamellar structure of the lipids. The lamellar lipid structure in the stratum corneum transformed to a disordered structure between 65 degrees C and 75 degrees C, the same temperature region at which a thermal lipid transition occurred. After cooling down to room temperature a recrystallization of at least a part of the lipids took place, after which only one unit cell with a repeat distance of 13.4 nm could be detected. Comparison of the scattering curve of the stratum corneum after crystallization with the scattering curve of the stratum corneum before recrystallization leads to the conclusion that in the original curve the lipids are arranged in two unit cells with repeat distances of 6.4 nm and 13.4 nm. From model calculations it appears that the latter unit cell consists of more than one bilayer. The scattering curves of stratum corneum hydrated to various levels were measured. A change in the water content of stratum corneum between 6% w/w and 60% w/w (fully hydrated) did not result in swelling of the bilayers, but the scattering curve obtained with stratum corneum hydrated to 60% w/w differed from those at lower hydration levels: the scattering curve at 60% w/w showed only the diffraction peaks corresponding to a unit cell with a repeat distance of 6.4 nm. This observation implies that the ordering of a part of the lipids is reduced at very high water contents, which may explain the strong penetration-enhancing effects of water in the stratum corneum. PMID- 1748811 TI - Contour mapping of the cutaneous microvasculature by computerized laser Doppler velocimetry. AB - A probe holder for laser Doppler velocimetry was designed to allow a narrow (1.24 mm) probe to be moved in increments of 1.04 mm, approximately the width of the probe window itself, so that four contiguous 1-mm2 spots in a 2.29 x 2.29 mm area could be sampled. An area as large as 2.48 x 2.48 cm can be measured with this device. The flux was fed into a computer by an analog/digital board, for visualization as a wave-form on the monitor, and for analysis by fast Fourier transforms and power spectrum analysis. Each spot sampled was given a unique x,y coordinate and the mean amplitude of the flux was designated as the z coordinate. With the aid of software, the values of these three coordinates were mathematically processed to produce contour graphs with shading that represented a map of the arteriolar circulation in the skin. This methodology allows for accurate movement and placement of the probe on the skin and the ability to relocate a spot within 1 mm of its original location after intervals of hours to days. Video images of the superficial plexus at the sites where the maps were made confirm the topographic appearance of these maps. Data generated by these maps raise the intriguing possibility that microcirculatory vessels may be engaged in a division of labor--some involved primarily with tissue perfusion, others with thermoregulation. PMID- 1748812 TI - Characteristics of vascular responses to endothelin-1 of simian digital arteries that distribute their branches to the skin. AB - Using the cannula-inserting method, vascular responses to endothelin-1 were investigated in the isolated and perfused simian digital artery. Endothelin-1 produced a strong and sustained vasoconstriction with EC50 of 5.15 +/- 1.24 ng. The endothelin-1-induced vasoconstriction was significantly inhibited in the Ca(++)-removed perfusate. It was partly attenuated by diltiazem, a potent Ca++ entry blocker, but not affected by alpha-adrenoceptor antagonist phentolamine, indicating that endothelin-1 causes vasoconstriction by either the extracellular Ca++ entry or intracellular movement of Ca++ from the cytosolic storage site. From these results, it is suspected that ET-1 is partially related to skin circulatory disturbances such as Raynaud's phenomenon. PMID- 1748813 TI - Conditioned medium from cultured human keratinocytes has growth stimulatory properties on different human cell types. AB - Evidence for growth-stimulatory properties of keratinocyte-conditioned medium (KCM) on human fibroblasts, endothelial cells, keratinocytes, smooth muscle cells, and a mouse fibroblast cell line (3T3 cells) is presented. On human fibroblasts KCM caused an increase of over 400% in DNA synthesis as revealed by 3H-thymidine incorporation and autoradiography. The proliferative effect was comparable to that of platelet-derived growth factor (PDGF), but was not inhibited by PDGF antibodies and exceeded that of transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and basic fibroblast growth factor (bFGF). Furthermore, KCM was found to stimulate smooth muscle cells, keratinocytes, and endothelial cells more potently than PDGF, EGF/TGF-alpha, and bFGF, respectively. KCM was also potent in stimulating thymidine incorporation in 3T3 cells, whereas EGF showed a twenty fold weaker stimulatory effect. Because keratinocytes have been shown to secrete TGF-alpha, which binds to the EGF receptor, binding of factors in KCM to the EGF receptor was assayed. The displacement of radiolabeled EGF by KCM corresponded to a low concentration of EGF (0.5 ng/ml), implying that the growth-stimulatory effect of KCM was not mediated via activation of EGF receptors. Taken together, these results suggest the presence of hitherto unidentified growth-stimulatory factor(s), expressed and secreted by cultured human keratinocytes. PMID- 1748814 TI - Comparison of minimal phototoxic dose and skin type for determining initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis. AB - Twenty-five patients with extensive psoriasis were randomly assigned into one of three groups, each receiving 0.5 mg/kg of oral liquid methoxsalen photochemotherapy followed 1 h later by exposure to long-wave ultraviolet light (UVA). The sole difference between the three groups was the method used to determine the initial UVA dose, which was either based on skin type, 25% of the minimal phototoxic dose (MPD), or 50% of the MPD. All patients were treated in the Phototherapy Unit at the Massachusetts General Hospital. Data were obtained until reaching the endpoint of clearance. At clearance, the results of the number of treatments required to clear, final UVA dose, cumulative UVA dose, and side effects were tabulated, compared, and analyzed for each of the three groups. The 25% and 50% MPD groups required a mean of 15.0 +/- 1.7 and 13.4 +/- 1.9 treatments to clear, respectively, as compared to the skin type group, which needed an average of 17.6 +/- 2.5 treatments. The mean final UVA dose was 7.4 +/- 0.9 J/cm2 and 8.4 +/- 1.4 J/cm2 for the 25% and 50% MPD groups, respectively, in contrast to 11.6 +/- 1.4 J/cm2 for the skin type group. The mean cumulative UVA dose at clearance for the 25% and 50% MPD groups was 79 +/- 16 J/cm2 and 87 +/- 27 J/cm2, respectively, versus 136 +/- 30 J/cm2 for the skin type group. The comparisons between the individual MPD groups and the skin type group did not achieve statistical significance with the exception of a marginally significant difference in final dose between the skin type group and the 25% MPD group (p = 0.06). However, the results of the two MPD groups were then pooled and the mean final (7.9 +/- 0.8 J/cm2) and cumulative (83 +/- 15 J/cm2) UVA doses were significantly (p = 0.04) and marginally significantly (p = 0.07) lower than the respective means of the skin type group. The number of treatments to clear, although lower in the pooled MPD groups (14.2 +/- 1.3) than in the skin type group, did not attain statistical significance (p = 0.19). Our data suggest that the MPD measurement may be superior to the skin-typing system when calculating the initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis. PMID- 1748815 TI - Thymidine salvage changes with differentiation in human keratinocytes in vitro. AB - We compared the capacity of proliferating and differentiating keratinocytes to salvage and catabolize extracellular thymidine. Both populations of cells catabolized thymidine to thymine and possessed thymidine phosphorylase activity. As keratinocytes differentiate, thymidine phosphorylase activity ultimately increased twofold. In contrast, proliferating and differentiating keratinocytes differed markedly in their capacity to salvage extracellular thymidine. Proliferating keratinocytes readily salvaged extracellular thymidine to form nucleotides, whereas differentiating cells rapidly lost this capacity. The inability of differentiating cells to form nucleotides from thymidine was not attributed to reduced availability of thymidine due to catabolism but rather was the result of the rapid loss of thymidine kinase activity. As keratinocytes differentiate in suspension culture, they lose 41% of thymidine kinase activity in 8 h and over 90% of activity in 12 h. Our data indicate that loss of capacity to salvage extracellular thymidine for synthesis of nucleotides closely parallels the onset of differentiation in keratinocytes. PMID- 1748816 TI - Identification of late differentiation antigens of human cornified epithelia, expressed in re-organized desmosomes and bound to cross-linked envelope. AB - Little is known about the process leading to desquamation in cornified epithelia. We describe late differentiation antigens (Ag) specific for human cornified squamous epithelia, defined by two murine monoclonal antibodies (MoAb), G36-19 and B17-21, produced after immunization with plantar stratum corneum (SC). Histologically, in epidermis both Ag are cytoplasmic in the lower stratum granulosum (SG), become pericellular in the upper SG, and progressively disappear in the lower SC. In contrast, they persist up to the desquamating corneocytes in the palmoplantar epidermis and hard palate epithelium, as well as in the three cornified epithelial components of the inner root sheath (IRS) of the hair follicle (HF). Cytologically, both Ag are expressed as surface spots only on rough corneocytes. They are largely preserved on cross-linked envelopes (CLE) of the fragile type. Ultrastructurally, both Ag appear in keratinosome-like cytoplasmic vesicles in the upper stratum spinosum (SS) and the SG keratinocytes, then are found in both the regular and reorganizing desmosomes of the SG keratinocytes, and lastly in the corneocyte-specific reorganized desmosomes we propose to name corneodesmosomes. On CLE, the Ag are located on fibrils gathered over the external side of the envelope. Immunochemically, the G36-19--defined epitope is sequential and shared by five non-cytokeratin protein antigens of molecular weight 33.5, 36.5, 40, 49, and 52 kD, the higher molecular weight polypeptides being possibly precursors of the 33.5-kD protein. In contrast, the B17-21 epitope, unaccessible by immunoblotting, is probably conformational. In long-term cultured keratinocytes, the Ag are only expressed when epidermal sheets are morphologically differentiated. The expression is enhanced in the absence of fetal calf serum (FCS) and of epidermal growth factor (EGF). G36-19 and B17-21 Ag participate in a corneodesmosome-CLE superstructure that is probably involved in corneocyte cohesiveness and partly responsible for the mechanical resistance of the SC. These Ag are relevant markers for studying desmosomal maturation during epidermal differentiation and desquamation. PMID- 1748817 TI - Effect of L-dopa methylester and glutathione depletion on murine B16BL6 melanoma growth in vitro. AB - The cytotoxic and growth-inhibitory effect of levodopa methylester (LDME) in murine B16BL6 (BL6) melanoma cells after glutathione (GSH) depletion was studied in vitro. Pretreatment of BL6 cells with 50 microM buthionine sulfoximine (BSO) depleted GSH content by nearly 90% and enhanced the growth-inhibitory effect of even a minimally cytotoxic concentration of LDME. Radiothymidine incorporation into BL6 cells significantly increased compared to untreated controls during the first 4 h of exposure to 0.2 mM LDME. However, pretreatment with BSO prevented this LDME-induced increase in radiothymidine incorporation. Because the percentage of cells in S-phase of the cell cycle was not altered, these results suggest that BSO exposure may be inhibiting unscheduled DNA synthesis, which could contribute to the cytotoxic effects of LDME. In addition, spectrophotometric studies indicated that in a cell-free system, GSH scavenged dopaquinone produced by the tyrosinase-mediated oxidation of LDME, presumably by formation of glutathionyldopa. Thus, enhancement of LDME cytotoxicity by BSO may also involve depleting the amount of GSH available for the nucleophilic addition to the quinone. PMID- 1748818 TI - Relation between the incidence and level of pigment cell antibodies and disease activity in vitiligo. AB - Patients with vitiligo often have antibodies to pigment cells. To examine whether there is a relation between the presence of such antibodies and disease activity, sera of 24 patients with vitiligo (10 with active and 14 with inactive disease) and 19 normal individuals were tested for antibodies to pigment cell surface antigens using a live cell enzyme-linked immunoabsorbent assay. IgG pigment cell antibodies were present in 80% (eight of 10) of patients with active vitiligo but in none of those with inactive disease or in normal individuals. The antibody level of patients with active vitiligo (mean binding index [BI] 3.3 +/- 0.59) was significantly higher than in patients with inactive disease (BI 0.96 +/- 0.04) or normal individuals (BI 1.0 +/- 0.04, p less than 0.001). Antibodies present in eight patients with high titers of pigment cell antibodies reacted to three of four pigment cells but to only one of six unrelated cells. These findings indicate that a correlation exists between the incidence and level of pigment cell antibodies and the activity of vitiligo, and support the hypothesis that vitiligo is an autoimmune disease mediated by an immune reaction to pigment cells. PMID- 1748819 TI - Low catalase levels in the epidermis of patients with vitiligo. AB - Suction blister roofs taken from the involved and uninvolved epidermis of patients with vitiligo showed a consistent reduction in levels of catalase compared to normal healthy controls of matched photo-skin types (Fitzpatrick classification). A decrease in catalase activity is expected to increase the concentration of hydrogen peroxide in the epidermis of these patients. Hydrogen peroxide functions as a reversible inhibitor of human tyrosinase with a KI of 8 X 10(-6) M. Also, hydrogen peroxide undergoes photochemical reduction yielding highly reactive hydroxyl radicals (OH.) and hydroxyl ions (OH-) mainly by the Haber-Weiss reaction. Hydroxyl radicals are capable of bleaching constitutional melanin and cause membrane lysis through lipid peroxidation reactions. Hydroxyl ions increase the pH in the epidermis, and as a consequence glutathione reductase activity is increased in patients with vitiligo compared to controls. Based on these new results, together with the previously reported calcium transport defect, a new hypothesis has been formulated for the pathogenesis of vitiligo. PMID- 1748820 TI - Do all epidermal keratinocytes contain parathyroid hormone related protein (PTHrP)? PMID- 1748821 TI - Comparison of methods for transfection of human epidermal keratinocytes. AB - Several methods for DNA-mediated cell transfection were tested to determine the optimal conditions for transfection of human epidermal keratinocytes. The following methods were compared: electroporation, lipofection, Ca3(PO4)2 co precipitation, DEAE-dextran, and polybrene-mediated transfection. The transfected DNA included human keratinocyte-specific promoter for keratin K14 as well as SV40 and RSV viral promoters. Enzyme assays and in situ staining were used to evaluate both quantitative and qualitative aspects of transfection, and both subconfluent and post-confluent, stratifying keratinocytes were examined. Lipofection, Ca3(PO4)2 co-precipitation, and polybrene methods transfect very efficiently, but lipofection is expensive and Ca++ in the co-precipitation procedure induces keratinocytes to differentiate. We have found that polybrene-mediated transfection followed by a 27% DMSO shock is optimal for introducing DNA into human epidermal keratinocytes. PMID- 1748822 TI - Isolation, detection, and amplification of intact mRNA from dermatome strips, epidermal sheets, and sorted epidermal cells. AB - Three different strategies for isolating RNA from epidermal cells were compared. Starting with dermatome sections frozen or disaggregated epidermal cells purified by fluorescence activated cell sorting (FACS), RNA was isolated with a guanidinium thiocyanate technique. Specific mRNA were detected by Northern blot analysis (involucrin, keratin 5, actin), or by reverse transcription and amplification with the polymerase chain reaction (PCR), using primers specific for keratinocyte products (keratins 1 and 14) and Langerhans cells (CD1a). Messenger RNA's characteristic of Langerhans cells and of keratinocytes at different stages of differentiation were detected in dermatome and epidermal sheet preparations as well as in FACS-separated cells. The use of snap-frozen dermatome sections allows the isolation of RNA from epidermis that has undergone minimal trauma and is very close to its in vivo state, but that includes RNA from some dermal cells. Extraction of RNA from Dispase-separated sheets involves slightly more manipulation of the epidermis but provides a sample free from dermal contaminants. PCR analysis of sorted epidermal cells is both sensitive and specific, but involves still greater manipulation. This final technique, however, allows the investigation of mRNA produced by small groups of epidermal cells that are still much closer to their in vivo state than if they had been cultured. By combining these techniques it is possible to determine the baseline production of specific mRNA in the skin in vivo and to assign their production to specific groups of cells with a sensitivity and specificity greater than any approach previously described. PMID- 1748823 TI - Construction of a full-length murine pro alpha 2(I) collagen cDNA by the polymerase chain reaction. AB - Construction of large collagen cDNA has been hindered by the relatively large size and high G-C content of processed mRNA. We describe here the development of a rapid and efficient method for obtaining large full-length collagen cDNA. A full-length (4.3 kb) murine pro alpha 2(I) collagen cDNA was constructed by synthesis of a first-strand cDNA library with use of poly-A RNA (MC3T3-E1) and the oligo-dT17-adapter primer described by Frohman et al (Proc Natl Acad Sci USA 85:8998, 1988). Pro alpha 2(I) collagen cDNA were specifically amplified by the polymerase chain reaction (PCR) with a pro alpha 2(I) specific primer as the 5' primer (20mer; corresponding to nucleotide positions 42-61 in the first exon of the murine pro alpha 2(I) collagen gene, COL1A2), and with the adapter sequence 5' to the dT17 as the 3' primer. The PCR conditions were optimized to allow amplification of the expected 4.0-5.0-kb product; a major 4.3-kb product was visualized by ethidium bromide, identified by in situ gel hybridization, and cloned. DNA sequencing determined that it contained the correct 5' sequence and the 3' end had a 68 basepair (bp) 3' untranslated region. The entire sequence that codes the amino-terminal propeptide domain has been determined and compared to the human sequence. The homology between human and mouse is less in the amino terminal propeptide than in the triple helical domain; exon 5 of murine COL1A2 codes for an additional six amino acids not found in human COL1A2. PMID- 1748824 TI - Activation of keratinocytes with psoralen plus UVA radiation induces the release of soluble factors that suppress delayed and contact hypersensitivity. AB - Exposure of mice to psoralen plus ultraviolet A (320-400 nm) radiation or midrange ultraviolet B (280-320 nm) radiation causes a systemic suppression of the immune response. Although the mechanisms involved in the induction of suppression are not entirely clear, recent studies have demonstrated that ultraviolet B--irradiated keratinocytes release soluble factors that depress delayed-type hypersensitivity to alloantigens and activate the suppressor cell pathway. The purpose of this study was to determine whether PUVA-treated keratinocytes could also cause the release of such immunosuppressive factors. Treatment of keratinocytes with psoralen and UVA radiation induced the release of a factor that depressed the delayed-type hypersensitivity reaction to alloantigen. The suppressive factor was released regardless of whether the psoralen formed monofunctional or bifunctional adducts with DNA and regardless of its phototoxicity. In addition, keratinocytes treated with psoralen and lower doses of UVA radiation released a factor that inhibited contact but not delayed type hypersensitivity, suggesting that more than one immunosuppressive factor is released following treatment of keratinocytes with appropriate doses of psoralen and UVA radiation. Our findings provide evidence that immunosuppressive factors released from keratinocytes may play a role in the induction of systemic immune suppression following PUVA treatment. Moreover, they demonstrate that PUVA treatment, unlike UVB treatment, can cause the release of more than one immunosuppressive factor from keratinocytes. PMID- 1748825 TI - The silent killer. PMID- 1748826 TI - Clinicopathological study of pancreatic carcinoma with particular reference to the invasion of the extrapancreatic neural plexus. AB - A clinicopathological study of 44 ductal carcinomas of the head of the pancreas revealed 39 with retroperitoneal invasion, of which 27 showed extrapancreatic plexus involvements. The second portion of the plexus pancreaticus capitalis was the most frequent site of invasion. A statistically significant correlation was found between neural invasion in the pancreatic tissue and plexus invasion, but no clear correlation was found between plexus invasion and lymphatic invasion or tumor size. Even small-sized tumors (t1) showed plexus invasion. The cases with plexus invasion had a statistically higher incidence of lymph-node involvement around the superior mesenteric artery than those without plexus invasion. These results indicate that complete dissection of extrapancreatic plexus around the superior mesenteric artery, including lymph nodes and soft tissue, could prolong the survival of patients with ductal carcinoma of the pancreas, even in cases of small-sized carcinomas. PMID- 1748827 TI - Cell-kinetic analysis of pancreatic cancers in Syrian golden hamsters. AB - Cell-kinetic analysis of pancreatic cancers using bromodeoxyuridine (BrdU) was performed on four transplantable pancreatic ductal adenocarcinomas, which were experimentally induced by giving N-nitrosobis (2-hydroxypropyl) amine (BHP) to Syrian golden hamsters. The volume-doubling time (Td) of the tumor was 0.43, 1.03, 2.30, and 3.50 d for tumor lines J, D, B, and F, respectively. In the pulse labeling study, the labeling index was 15.8, 23.3, 27.9, and 31.7, respectively. The most rapidly growing tumor line, J, unexpectedly showed the lowest BrdU labeling index (LI). The further study of tumor using the cumulative-labeling method revealed that the duration of S phase (Ts), the generation time (Tg) and the growth fraction (GF) were 2 h, 14 h, and 90% for tumor J and 12 h, 37 h, and 85% for slowly growing tumor B, respectively. Cells of limited life span (CLLS) of these lines did not differ from each other. These results conclude that the marked difference of Tg between tumor lines J and B resulted in a distinction of their growth rates. The disagreement of Ts/Tg also lead to a reversion of LI between the two lines. Furthermore, LI of BrdU with one-point pulse labeling did not seem to be a sufficient indicator of the growth characteristics, at least, in the present experiment. PMID- 1748828 TI - Glucose-dependent effects of pancreastatin on insulin and glucagon release. AB - Pancreastatin (PST), a peptide isolated from porcine pancreas in 1986, has been reported to inhibit insulin and to stimulate glucagon secretion. Since both of these effects have been questioned, we investigated the effect of PST (20, 200, or 2000 pM) on hormone release in the isolated perfused rat pancreas at different glucose levels (1.7, 5.5, 11.1, and 16.7 mM). At 1.7 mM glucose, 20 pM PST had no significant effect on glucagon secretion, whereas 200 pM and 2 nM PST significantly inhibited glucagon release. At a concentration of 5.5 mM glucose, insulin output was not affected by PST in any of the concentrations tested. At 11.1 mM glucose, however, 200 pM and 2 nM PST significantly inhibited insulin output. At 16.7 mM glucose, insulin secretion was significantly reduced by all concentrations of PST tested. Unstimulated exocrine pancreatic secretion was not affected by PST in any of the experimental settings. We conclude that PST inhibits glucagon and insulin secretion dose-dependently, and these effects apparently are glucose-dependent. PST does not influence basal exocrine pancreatic secretion in vitro. PMID- 1748829 TI - Multifocal pancreatic serous cystadenoma with atypical cells and focal perineural invasion. AB - A case of multifocal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The distal common bile duct was obstructed, and the proximal bile duct was remarkably dilated on cholangiography. The main portal vein was obstructed and collateral vessels had developed on portal angiography. Total pancreatectomy was performed. The resected specimen contained one tumor in the head of the pancreas, five in the body, and one in the tail. The tumors of the head and body were morphologically the same. Microscopically, both contained spongelike multilocular cysts on their cut surfaces. These cysts were covered with low cuboid epithelium containing clear cytoplasm and abundant glycogen. Neural invasion was also found. The tumor cells exhibited an increased N/C ratio, variable nuclear size, irregular nuclear margins, and coarse nuclear chromatin. These tumors had aneuploid nuclear DNA with a DNA index of 1.9 and a proliferation index of 0.28. We feel that it is necessary to reconsider the biological concept of serous cystadenoma. PMID- 1748830 TI - Are Kentuckians using advance medical directives? AB - Findings of a statewide survey indicate that only 9% of Kentucky adults are completing Living Wills and an equal percent are designating Health Care Surrogates. Designed to protect patient's rights of self-determination in treatment decisions and protect physicians and other health care professionals from liability in complying with patient wishes, only 37% of the state's residents know about Kentucky's Living Will and 24% known about the Designation of Health Care Surrogate. In view of the results, it is recommended that educational efforts be undertaken, changes in legislation occur to ease advance medical directive access and use, and that, following customary medical practice, legislation be enacted to provide authorization of family members to serve as substitute health care decision makers for incapacitated patients. PMID- 1748831 TI - Acquired factor VIII inhibitor. AB - Development of a circulating inhibitor of the coagulant activity of factor VIII is a rare event producing a clinical picture similar to that of classic hemophilia. A case of autoimmune factor VIII inhibitor has been presented. Although a hemostatic response was rapidly achieved with the infusion of factor IX concentrates, immunosuppressive therapy was initiated. The inhibitor disappeared in less than 20 days from the initiation of therapy. PMID- 1748832 TI - Thoracic empyema due to Streptococcus intermedius. AB - With improved laboratory identification procedures, Streptococcus milleri (intermedius) is becoming recognized as an important human pathogen with the potential to form abscesses in a wide range of organs. The occurrence of a rapidly progressive and toxic empyema due to this organism in an otherwise healthy young adult without a predisposing lower respiratory tract infection allows us to examine the possibility that this microbe may be a significant but frequently unrecognized cause of adult empyema. PMID- 1748833 TI - Yellow nail syndrome: a perspective. AB - The Yellow Nail syndrome is an unusual lymphangitic disorder classically characterized by the presence of nail discoloration, lymphedema and pleural effusion. Since the recognition of the significance of these associated physical findings, four cases have been diagnosed at our institution in the last six years. This suggests that the syndrome may not be as rare as previously reported in medical literature. More often it may remain unrecognized in the absence of the classic triad of physical findings. To heighten awareness of this disorder, we describe our most recent patient diagnosed with YNS and provide a review of the current medical literature. PMID- 1748834 TI - Medical cost containment--the issues for 1992. PMID- 1748835 TI - The Kentucky Cancer Program. PMID- 1748836 TI - Economic disclosure and economic advocacy. New duties in the medical standard of care. PMID- 1748837 TI - Cruzan v. Director, Missouri Department of Health. Too much ado. PMID- 1748838 TI - The experimental treatment exclusion clause. A tool for silent rationing of health care? PMID- 1748839 TI - Dynamics of human neutrophil aggregation evaluated by flow cytometry. AB - In order to directly monitor neutrophil aggregation, we have developed a simple particle counting technique using flow cytometry. Flow times were used to determine aggregation from changes in the total number of particles per unit volume (%PA(T)), while fluorescent signals emitted from glutaraldehyde-fixed neutrophils were used to measure changes in the total number of singlet neutrophils (%PA(S)). Flow cytometrically-determined %PA values were found to be virtually identical to values determined from microscopy. We show that aggregation parameters can be evaluated and compared simply from measures of changes in total particle count without a need for distinguishing singlets from multiplets. A number of aggregation parameters are introduced and related to the initial cell concentration (N(o)) and stir speed (shear). Aggregation of neutrophils, following stimulation with 0.5 microM FMLP (N-formyl-methionyl leucyl-phenylalanine), showed a latent time (tl) of 4 +/- 1.5 sec independent of N(o) or stir speed; had a forward rate of aggregation (vf) which was proportional to the initial cell concentration and the stir speed; plateaued for greater than or equal to 60 s; and showed partial to complete reversal by 7.5 min. Above a critical stir speed, the extent and duration of aggregation varied inversely with the stir speed. The stir and N(o) dependence of the aggregation parameters studied suggest the existence of subpopulations of neutrophils with distinct efficiencies of aggregation. PMID- 1748840 TI - Activation of human neutrophils by phorbol ester decreases the cytoplasm compactness and the lactoferrin content of the granulocytes. AB - Human neutrophils isolated from the blood were incubated in vitro for 30 min with 25 ng/ml of phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, to study its effect on the fine structure of granulocytes and on the subcellular distribution of lactoferrin (Lf). Flow cytometry analysis of the human neutrophils showed that PMA induced a decrease in size and granularity of the cells. By electron microscopy, the PMA-treated cells showed numerous empty vesicles, smoothing of the cell surface, and a marked decrease in the compactness of the cytoplasmic ground substance. High-resolution immunogold ultracytochemistry showed that neutrophils lost most of their content in Lf after the PMA incubation. In thin sections, the cytoplasmic compartment of PMA-treated neutrophils contained an average of 1.03 +/- 0.3 Lf-positive vesicles per microns 2, whereas control granulocytes showed an average of 5.72 +/- 1.49 Lf vesicles per microns 2 of cytoplasm. Most of PMA-treated neutrophils kept some Lf-positive vesicles; a significant minority (10-15%) of the granulocytes showed cytological features of cell death. We conclude that the PMA-induced neutrophil activation is associated with microanatomical changes that include i) exocytosis of most, but not all, of the Lf-bearing vesicles; ii) rounding up of the cell outline; and iii) decrease in the compactness of the cytoplasmic ground substance. PMID- 1748841 TI - Kinetics of the biosynthesis of complement subcomponent C1q by murine macrophages: LPS, immune complexes, and zymosan alone and in combination with interferon-gamma. AB - We investigated the effects of bacterial lipopolysaccharide (LPS), immune complexes (IC), and C3b opsonized zymosan (AZ) alone and in combination with interferon-gamma (IFN-gamma) priming on macrophage synthesis and secretion of C1q. Our results indicated that LPS, IC, and AZ alone stimulated C1q mRNA and secretion in the absence of IFN-gamma. The increase in mRNA accumulation was detectable after 3 h, peaked at 6 h and was maintained at constitutive levels for 24 h. There was a corresponding early burst of increased secretion of functional C1q after 3 to 6 h which declined rapidly after 9 to 24 h culture of LPS stimulated macrophages. Priming of macrophages with IFN-gamma and simultaneous triggering with LPS, IC, or AZ produced additive rather than synergistic increases in C1q mRNA accumulation. These same agents inhibited constitutive secretion of C1q in the absence of IFN-gamma priming as determined by autoradiographic analysis of metabolically radiolabeled secretory C1q. Triggering of IFN-gamma primed macrophages with LPS, IC, or AZ also markedly suppressed the increased rate of C1q secretion induced by IFN-gamma in a dose-related fashion. A corresponding dose-dependent increased accumulation of endogenous C1q in cell lysates was detected by Western blot analysis of macrophages which had been stimulated by LPS, IC, or AZ alone or in combination with IFN-gamma. Our findings indicate that LPS as well as FcR and C3bR triggering agents stimulate early and sustained C1q synthesis accompanied by an early and short-lived burst of C1q secretion which rapidly diminished and results in an increased intracellular accumulation of C1q due to ongoing synthesis. IFN-gamma appeared to further amplify the same kinetics of increased C1q mRNA accumulation and decreased extracellular accumulation mediated by LPS, IC, and ZM. Our results suggest that LPS, IC, and AZ alone or in combination with IFN-gamma stimulate early C1q production to modulate macrophage effector functions followed by an inhibition of C1q secretion when the activation process has been culminated. PMID- 1748842 TI - Leukocyte-endothelial cell adhesive interactions: role of xanthine oxidase derived oxidants. AB - The objective of this study was to determine whether agents that either scavenge or inhibit the production of oxygen radicals can alter the adhesive interactions between leukocytes and venular endothelium elicited by ischemia-reperfusion. Cat mesenteric and intestinal blood flows were reduced to 20% of baseline for 1 hr, followed by 1 hr of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either manganese-superoxide dismutase (Mn-SOD), catalase, desferrioxamine, or oxypurinol was administered intravascularly. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. Catalase, Mn-SOD, and oxypurinol significantly attenuated neutrophil adherence while neither inactivated-catalase nor desferrioxamine altered the reperfusion-induced leukocyte adhesion. The ratio of Vw to erythrocyte velocity, an index of the fracture stress between rolling leukocytes and venular endothelium, was not altered by any of the agents studied. These results and data in the literature indicate that many of the agents that are commonly used to either scavenge or inhibit the production of oxygen radicals in postischemic tissues exert a significant inhibitory influence on leukocyte adhesion to microvascular endothelium in vivo. Our results are also consistent with the view that xanthine oxidase-derived oxidants contribute to the leukocyte endothelial cell adhesive interactions associated with reperfusion of ischemic tissues. PMID- 1748843 TI - Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis. AB - Herein we demonstrate that continuous infusion of either TNF-alpha or IFN-gamma (10(4) U/day) via osmotic micropumps leads to an increased resistance of mice infected with a lethal dose (10(7)) of M. tuberculosis H37Rv, associated with a decreased microbial growth in all target organs. This result was reinforced by the finding that infusion of antibodies against TNF-alpha or IFN-gamma greatly enhanced susceptibility of naive mice to tuberculosis. In a final set of experiments, using neutralizing antibodies, we show that IFN-gamma, not TNF-alpha is involved in determining acquired resistance against murine tuberculosis, as seen by the fact that acquired immunity is resistant to anti-TNF-alpha antibodies, yet sensitive to anti-IFN-gamma antibodies. This suggests a role for both IFN-gamma and TNF-alpha in determining innate resistance whereas IFN-gamma may be the mediator of the anamnestic response. PMID- 1748844 TI - Independence of the pattern of early cytokine release from autoregulation by nitric oxide. AB - The L-arginine-dependent tumor cell cytotoxicity produced by activated macrophages (M phi) may be mediated either directly by production of nitric oxide (NO), or by induction of NO synthesis in the tumor cell. The influence of M phi NO synthesis on the release of soluble cytotoxic mediators was investigated in this study. The synthesis of M phi NO, measured as nitrite, was detected 6 h after lipopolysaccharide (LPS)-triggering and reached a peak level by 44 h. A concurrent decrease in M phi viability beginning at 18 h after triggering was detected during a period of 72 h in culture. Both the production of NO and loss of viability correlated with the presence of L-arginine in the incubation media and was inhibited by NG-monomethyl-L-arginine (NMA). The medium in which LPS triggered adherent peritoneal exudate cells were incubated was examined for the presence of tumor necrosis factor (TNF), gamma interferon (IFN-gamma), and the soluble mediators that induce mitochondrial respiratory inhibition in tumor cells. All of these effector molecules were released at peak levels into the conditioned supernatants within 12 h after LPS-triggering. The peak level obtained for each effector molecule was influenced by the media in which the M phi was incubated; however, no correlation was detected between the level of cytokines produced and the synthesis of nitrite by the M phi indicating that NO synthesis has no inhibiting effect on the initial burst of cytotoxic factors released. PMID- 1748845 TI - Using neural networks to diagnose cancer. AB - While artificial brains are in the realm of science fiction, artificial neural networks (ANNs) are scientific facts. An artificial neural network is a computational structure modeled somewhat on the neural structure of the brain; both have many highly interconnected processing elements. These biologically inspired processing elements are taught by feeding examples until the results are acceptable. In the past 5 years, neural networks have become successful in providing meaningful second opinions in clinical diagnosis. In our research, a prototype artificial neural network was trained on numeral ultrasound data of 52 actual cases and then correctly identified renal cell carcinoma from renal cysts and other conditions without diagnostic errors. Our nonlinear artificial neural network was trained on software using the standard backpropagation paradigm on a 80386 microcomputer. Our ANN learned from ultrasound data in 52 cases (17 malignant, 30 cysts, and 5 other) at a Memphis hospital. The trained prototype performed without error on 47 cases which were not in the data used for training. This prototype must be validated by extending this study to more cases. PMID- 1748846 TI - Analog-to-digital clinical data collection on networked workstations with graphic user interface. AB - An innovative respiratory examination system has been developed that combines physiological response measurement, real-time graphic displays, user-driven operating sequences, and networked file archiving and review into a scientific research and clinical diagnosis tool. This newly constructed computer network is being used to enhance the research center's ability to perform patient pulmonary function examinations. Respiratory data are simultaneously acquired and graphically presented during patient breathing maneuvers and rapidly transformed into graphic and numeric reports, suitable for statistical analysis or database access. The environment consists of the hardware (Macintosh computer, MacADIOS converters, analog amplifiers), the software (HyperCard v2.0, HyperTalk, XCMDs), and the network (AppleTalk, fileservers, printers) as building blocks for data acquisition, analysis, editing, and storage. System operation modules include: Calibration, Examination, Reports, On-line Help Library, Graphic/Data Editing, and Network Storage. PMID- 1748847 TI - The use of X-terminals as clinical workstations. AB - The Medical Computer Facility at the Fox Chase Cancer Center has installed X terminals in patient examination rooms and at nursing stations for clinical data access by physicians and nurses. The X-terminals are connected to UNIX operating system RISC processors via Ethernet. The RISC processors communicate with databases on a minicomputer cluster. Simultaneous presentation of textual (e.g., pathology and radiology reports) and graphical (e.g., clinical laboratory results) clinical data is provided under X-Windows. CT and MRI images can also be displayed in windows. Our experiences implementing X-terminal clinical workstations in a production environment will be discussed. PMID- 1748848 TI - A new teaching tool for dental and medical schools: multimedia CD-ROM on dental and skeletal development. AB - Multimedia teaching tools in Medicine are still very rare. Their presentation on a CD-ROM format is part of the emerging technologies in Medical Informatics. The Multimedia material presented here on Dental and Skeletal Development is mostly a Database and a Tutorial. The Database, which contains more than 2000 hand/wrist radiographs, is mostly intended for Pediatricians, Endocrinologists, Forensic Dentists and Physicians, as well as for Orthodontists and Pedodontists. The material is the result of 20-year of Longitudinal Growth study of children in Montreal. In this Multimedia CD-ROM, the research results are used for Medical teaching purposes. PMID- 1748849 TI - A model for designing intelligent tutoring systems. AB - A model for the design of an intelligent tutoring system is presented using artificial intelligence techniques and cognitive processing theories. The model of cognitive processing known as the Knowledge Acquisition and Recall Theory is derived from Anderson's Adaptive Control of Thought Theory. The model is used as a basis for a methodology for the design of an intelligent tutoring system that teaches problem-solving strategies for blood grouping discrepancies. The system developed was tested to determine the effectiveness of the methodology developed and to provide support for the concepts in the model of cognition developed. The preliminary results provide some evidence that an intelligent tutoring system designed using the methodology developed may aid in the knowledge acquisition process. (knowledge acquisition, artificial intelligence, computer-assisted instruction, cognition, intelligent tutoring system). PMID- 1748850 TI - Automated analysis of medical text. II. Cognitive strategy. AB - In a previous paper, the authors described three paradigms applicable to automated medical text analysis. In this paper, the relative importance of the three paradigms is discussed, viz. the relative value of the linguistic word categorization, the semantic paradigm, and the medical fact delineation. The strategy adopted was to limit the linguistic disambiguation and apply probabilistic rules, in order to speed up the analytic process. PMID- 1748851 TI - Pathologic elements in the planning of information systems: the case of hospitals in Quebec. AB - The existing usage of information technology for information systems in hospitals draws attention to the fact that: (a) health care units which operate sophisticated numerical instrumentation to support medical activities rarely employ computers for the management of their operations and (b) despite the availability of affordable information technologies (microcomputers, networks, etc.), few hospitals include such elements as health care unit management in the development of their information systems portfolio. Is this paradoxical situation a result of the planning methodologies or of factors affecting their use? Or can it be attributed to the failure of present planning methodologies to incorporate the diversity of computerization approaches of the various stakeholders involved? If this is the case, untapped potential computerization possibilities exist that could lead to the development of hospital services and increased organizational efficiency. PMID- 1748853 TI - 182nd meeting of the Society for Endocrinology. 13-15 November 1991. Abstracts. PMID- 1748854 TI - Atherothrombotic mechanisms in smoking. PMID- 1748852 TI - Iliad training enhances medical students' diagnostic skills. AB - Iliad is a computerized, expert system for internal medical diagnosis. The system is designed to teach diagnostic skills by means of simulated patient case presentations. We report the results of a controlled trial in which junior students were randomly assigned to received Iliad training on one of two different simulated case mixes. Each group was subsequently tested in both their "trained" and "untrained" case domain. The testing consisted of computerized, simulated patient cases for which no training feedback was provided. Outcome variables were designed to measure the students' performance on these test cases. The results indicate that students made fewer diagnostic errors and more conclusively confirmed their diagnostic hypotheses when they were tested in their trained domain. We conclude that expert systems such as Iliad can effectively teach diagnostic skills by supplementing trainees' actual case experience with computerized simulations. PMID- 1748855 TI - T-cell vaccination in immunological disease. PMID- 1748856 TI - High coronary mortality in cold regions of Sweden. AB - The hypothesis that cold climate is associated with high coronary mortality in Sweden is tested. Cold exposure was calculated in each of the 284 municipalities of Sweden. There was a significant association between cold exposure and coronary mortality in both sexes in all age groups. The strongest association was found in men aged 40-64 years (coefficient of determination k = 0.39). The decile of men aged 40-64 years who lived in the coldest municipalities had a 40% excess mortality. A significant association was also found between cold exposure and mortality from cerebrovascular diseases. We conclude that there is a strong regional association between cold exposure and high coronary mortality. PMID- 1748857 TI - Water hardness does not contribute substantially to the high coronary mortality in cold regions of Sweden. AB - Earlier studies have shown an association between cold climate and high coronary mortality. The aim of this study was to elucidate in more detail the effect of drinking water hardness on this association. Drinking water parameters were obtained from 259 municipalities in Sweden over a 10-year period. During the same period a 'cold index' was calculated for each municipality. Standardized coronary mortality rates in men aged 40-64 years were used. A negative association was found between water hardness and coronary mortality (coefficient of determination k = 0.080). A much stronger association was found between coronary mortality and cold index (D = 0.389). When coronary mortality was explained by both water hardness and cold index, the association was not significantly strengthened (D = 0.391). Water hardness was negatively correlated with cold index (r = 0.55). We conclude that the association between cold climate and coronary mortality was stronger than that between drinking water hardness and coronary mortality, and that it persisted after stratification for water hardness. PMID- 1748858 TI - Cardiac left ventricular function before and during early thyroxine treatment in severe hypothyroidism. AB - In some patients with severe hypothyroidism, thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even cured. Cardiac function in eight severely hypothyroid patients was studied by means of radionuclide ventriculography (RNV) at rest and during supine bicycle exercise before thyroxine treatment, and repeated during treatment before and after administration of 160 mg of oral verapamil. There was an exercise-induced fall in left ventricular ejection fraction (LVEF) in two patients before therapy, and in two additional subjects after 17 d on suboptimal doses of thyroxine. Verapamil attenuated the fall and induced a significant increase in LVEF during exercise (P less than 0.014). No abnormal regional cardiac wall movement (RWM) was observed. After 2 months of thyroxine treatment, LVEF increased significantly during exercise both before and after verapamil (P less than 0.012 and P less than 0.005). These findings are indicative of reversible coronary artery dysfunction. We recommend that, if feasible, thyroxine should be supplemented with verapamil during the early phase of treatment. PMID- 1748859 TI - The role of paid work in Swedish chronic dialysis patients--a nation-wide survey: paid work and dialysis. AB - The role of paid work in chronic illness has been investigated in this nation wide study of all Swedish-speaking patients on chronic dialysis above the age of 16 years, who were not too tired or severely ill to participate and who had been treated for at least 3 months. Young age and female gender were consistently associated with increased prevalence of self-reported depression, poor psychological health, psychosomatic symptoms and sleep disturbance. In multivariate analyses paid work, strong emotional support, and care at intermediate or small units were independently associated with a good quality of life. Chronic dialysis patients who did paid work (19.6% of the patients below 65 years of age) perceived their work as more socially supportive than did men and women in the normal working population. It may be concluded that paid work is of particular importance to this patient group because it may give extra social support to patients whose social network is in general rather poor. PMID- 1748860 TI - Effect of pancreas transplantation on glucose counterregulation in insulin dependent diabetic patients prone to severe hypoglycaemia. AB - Pancreatic transplantation was performed in three patients with insulin-dependent diabetes mellitus in whom recurrent and severe episodes of hypoglycaemia had been found to be due to defective glucose counterregulation. Thus in these patients the spontaneous blood glucose recovery after insulin-induced hypoglycaemia (0.1 U kg-1 h-1 i.v. insulin until blood glucose levels fell below 2.8 mmol l-1) was delayed, and the responses of glucagon, epinephrine and growth hormone (GH) were absent or diminished. After pancreas transplantation the patients exhibited essentially normal blood glucose control. When the insulin infusion test was repeated 3 months after the transplantation, the blood glucose level recovered rapidly after insulin withdrawal. The glucagon response was restored, and the responses of epinephrine and GH were improved. Plasma C-peptide was suppressed by approximately 50%, which is less than is observed in normal subjects. It is concluded that glucose counterregulation improves after pancreas transplantation. This appears to be mainly due to an improvement in the hypoglycaemia-induced glucagon response, but an amelioration of sympatho-adrenal and hypothalamic pituitary regulatory mechanisms may also be involved. The apparent failure to suppress completely the insulin release from the denervated pancreas transplant indicates that inhibition of beta-cell secretion during insulin-induced hypoglycaemia may be partly under neural control. PMID- 1748861 TI - Acute fungal thyroiditis in a patient with acute myelogenous leukaemia. AB - Acute suppurative thyroiditis of any origin is uncommon, but fungal infections of the gland are particularly rare. Haematogenous spread is the usual route of infection. We here present the case of a recently encountered patient with neutropenic fever and Candida thyroiditis. Fine-needle aspiration biopsy greatly aided the diagnosis. In immunocompromised patients, the specimens should be treated with special stains to detect the presence of opportunistic organisms; if any are found, appropriate therapy should be initiated. PMID- 1748862 TI - Diclofenac-induced thrombocytopenic purpura with renal and hepatic involvement. AB - A case of diclofenac-induced thrombocytopenic purpura in a 59-year-old woman is described. Unlike the majority of earlier cases, ours was associated with renal insufficiency and jaundice. Despite the dramatic clinical picture, with severe thrombocytopenia and marked renal insufficiency, the prognosis appears to be excellent, as is shown in our case and in similar ones reported in the literature. A high dose of steroids is the treatment of choice. PMID- 1748863 TI - The response of paraneoplastic fever of lymphomas and solid tumours to the administration of naproxen. PMID- 1748864 TI - Activity of antibiotics against various strains of clinically isolated glucose non-fermenting gram-negative bacteria. PMID- 1748865 TI - Non-functional expression of Escherichia coli signal peptidase I in Bacillus subtilis. AB - The Escherichia coli lep gene, encoding signal peptidase I (SPase I) was provided with Bacillus subtilis transcription/translation signals and expressed in this organism. When present on a low-copy-number plasmid, the amount of E. coli SPase I produced (per mg cell protein) in B. subtilis was half that produced in wild type E. coli cells. The production of E. coli SPase I in B. subtilis was increased approximately fivefold by cloning the lep gene into a high-copy-number plasmid. The expression of E. coli SPase I in B. subtilis did not appear to increase the rate of processing of two hybrid secretory precursor proteins. Two observations may explain the failure of E. coli SPase I to stimulate processing of exported proteins in B. subtilis. First, the E. coli SPase I was apparently not exposed on the outside of the B. subtilis cytoplasmic membrane, indicating its incorrect insertion into the membrane. Second, in vitro processing studies, using cell-free extracts of B. subtilis producing E. coli SPase I, suggested that the enzyme was not active. A further outcome of this study was that conditions favouring processing of precursors by SPase I in cell-free extracts of E. coli did not favour processing by the corresponding enzyme in B. subtilis cell-free extracts. This suggests that significant differences exist between the two enzymes. The observation that antibodies directed against E. coli SPase I did not cross-react with B. subtilis membrane proteins supports this idea. PMID- 1748866 TI - Structural organization of the Corynebacterium glutamicum plasmid pCG100. AB - pCG100, a 3 kb cryptic plasmid of Corynebacterium glutamicum ATCC 13058, probably identical with pSR1 from C. glutamicum ATCC 19223, was characterized. The minimum region for autonomous replication was shown to be contained on a 1.9 kb BglII NcoI fragment; a 380 bp HindIII-SphI fragment can replicate in the presence of the parental plasmid, which presumably provides a trans-acting replication factor. Derivatives of pCG100 are able to replicate in several Corynebacterium, Brevibacterium and Arthrobacter strains. pCG100 is compatible with pBL1, a cryptic plasmid of Brevibacterium lactofermentum. Shuttle plasmid vectors, containing the kanamycin-resistance gene from Tn903 or from Streptococcus faecalis as selectable markers and the AmpR, TetR or lacZ alpha genes for insertional inactivation, were constructed using the minimum replication fragment of pCG100. PMID- 1748867 TI - Identification of three gene regions associated with virulence in Dichelobacter nodosus, the causative agent of ovine footrot. AB - Dichelobacter nodosus (formerly Bacteroides nodosus) is a Gram-negative strict anaerobe and is the primary pathogen involved in ovine footrot. A comparative hybridization strategy was used to isolate recombinant clones which hybridized to DNA from a virulent strain of D. nodosus but not with a benign isolate. Three virulence-associated gene regions were identified and one of these regions was shown to be present in multiple copies in the D. nodosus genome. Hybridization studies on 101 clinical isolates of D. nodosus showed that these strains could be divided into three hybridization categories which could be correlated with the virulence of the isolates. The recombinant clones have considerable potential for the development of a gene-probe-based method for the differential diagnosis of ovine footrot. PMID- 1748868 TI - Lysogeny in Leuconostoc oenos. AB - Thirty strains of Leuconostoc oenos were exposed to mitomycin C to induce lysogenic bacteriophages. Lysis curves typical for lysogenic strains were obtained with 19 strains. Indicator strans were found for 17 of these phages. Five were characterized by electron microscopy, lytic spectrum, molecular masses of the proteins, sequencing of five N-terminal amino acids of the two major proteins and DNA analysis (restriction patterns, cross hybridization). The results revealed a very close relationship between the phages. Hybridization experiments between the DNAs of the temperate phages and the appropriate lysogenic strains revealed phage-related sequences in the DNA of the lysogenic strain. PMID- 1748869 TI - Resistance of Streptomyces cinnamonensis to butyrate and isobutyrate: production and properties of a new anti-isobutyrate (AIB) factor. AB - Butyrate and isobutyrate (after isomerization to n-butyrate) are specific precursors for the biosynthesis of monensin A in Streptomyces cinnamonensis. High concentrations of both butyrate and isobutyrate (greater than 20 and 10 mM, respectively) were toxic to S. cinnamonensis plated on solid medium. Spontaneous mutants resistant to these substances were isolated. These new strains produced monensins at even higher concentrations of butyrate or isobutyrate, with an increased yield of monensin A. S. cinnamonensis produced an anti-isobutyrate (AIB) factor, which was originally found to be excreted by some isobutyrate resistant stains growing on solid medium containing isobutyrate. On plates, the AIB factor efficiently counteracted toxic concentrations not only of isobutyrate, but also of acetate, propionate, butyrate, 2-methylbutyrate, valerate and isovalerate against S. cinnamonensis as well as other Streptomyces species. Although the AIB factor enabled normal growth, sporulation and monensin production on plates, it did not have positive effects on submerged cultures of S. cinnamonensis with isobutyrate. The partial purification of the AIB factor was achieved. The role of the AIB factor during spore germination on solid medium containing isobutyrate or its homologues is discussed. PMID- 1748870 TI - In vitro characterization of intra-generic inhibition of growth in Salmonella typhimurium. AB - The intra-generic inhibition of bacterial growth observed previously in vivo and in vitro with strains of Salmonella, Citrobacter and E. coli was studied in vitro using S. typhimurium strain F98. There was complete inhibition of multiplication of S. typhimurium when it was added to stationary-phase broth cultures of different Salmonella serotypes, but only partial inhibition when added to broth cultures of E. coli. The degree of inhibition between different mutants of F98 was affected by the numbers of bacteria of the inhibiting strain, but this was not the only factor, since exponential-phase bacterial cells were less inhibitory than stationary-phase cells. The inhibitory effect was produced at temperatures between 20 degrees C and 40 degrees C. The complete inhibition of growth observed between F98 mutants was abolished by ampicillin, rifampicin and streptomycin, but not by nalidixic acid. Inhibition was also prevented by separating the two cultures by a dialysis membrane. A TnphoA insertion mutant of F98 was produced which did not show inhibition in vitro but was still inhibitory in vivo. It is suggested that this complete inhibition of bacterial multiplication between organisms of the same genus, which is greater than that produced between organisms from different genera, is mediated by a cell surface protein. PMID- 1748871 TI - Synergistic action of nikkomycin X/Z with azole antifungals on Candida albicans. AB - Fluconazole, ketoconazole and tioconazole were shown to act synergistically in vitro with the antibiotic nikkomycin X/Z on the pathogenic fungus Candida albicans. The phenomenon was demonstrated using a checkerboard technique and growth inhibition experiments. The azole antifungal agents, even at concentrations not affecting growth, decreased the incorporation of the 14C-label from [14C]glucose into chitin of the candidal cell wall. After 3 h incubation with tioconazole, 1 microgram ml-1, the incorporation of the radiolabelled glucose into chitin of intact cells and regenerating spheroplasts of C. albicans was inhibited by 43% and 30%, respectively. Moreover, the relative chitin content was approximately 45% lower than that of control cells. The chitin content increased after prolonged incubation with azoles, thus confirming the known phenomenon of azole-induced uncoordinated chitin synthesis and deposition. On the other hand, azole derivatives had very little effect on the rate of nikkomycin transport into C. albicans cells. A sequential blockade mechanism of synergism is proposed. PMID- 1748872 TI - Regulation of chitinase synthesis in Trichoderma harzianum. AB - The production of chitinase by Trichoderma species is of interest in relation to their use in biocontrol and as a source of mycolytic enzymes. Fourteen isolates of the genus were screened to identify the most effective producer of chitinase. The best strain for chitinase was Trichoderma harzianum 39.1, and this was selected for study of the regulation of enzyme synthesis. Washed mycelium of T. harzianum 39.1 was incubated with a range of carbon sources. Chitinase synthesis was induced on chitin-containing medium, but repressed by glucose and N acetylglucosamine. Production of the enzyme was optimal at a chitin concentration of 0.5%, at 28 degrees C, pH 6.0 and was independent of the age of the mycelium. The synthesis of chitinase was blocked by both 8-hydroxyquinoline and cycloheximide, inhibitors of RNA and protein synthesis, respectively. The mode of chitinase synthesis in this fungus is discussed. PMID- 1748873 TI - Defective mycolic acid biosynthesis in a mutant of Mycobacterium smegmatis. AB - A mutant of Mycobacterium smegmatis defective in mycolic acid biosynthesis was isolated following chemical mutagenesis. Fatty acids were extracted from the mutant and subjected to structural analysis by thin-layer chromatography and high performance liquid chromatography (HPLC) of both methyl and p-bromophenacyl ester derivatives. Thin-layer chromatography did not show the presence of any fatty acid of RF comparable to that of standard methyl mycolate. The HPLC profile revealed a broad peak in the standard mycolic acid ester region. No characteristic peaks of mycolic acid esters comparable to the wild-type could be resolved. Mass spectral analysis of the HPLC-purified peak demonstrated the presence of shorter-chain fatty acids in the mutant. These data support the idea that the mutant accumulates precursors of mycolic acids and is incapable of carrying out the final conversion to mycolic acids of 60-90 carbon atoms. PMID- 1748874 TI - Physiological regulation and optimization of lipase activity in Pseudomonas aeruginosa EF2. AB - Physiological regulation of extracellular lipase activity by a newly-isolated, thermotolerant strain of Pseudomonas aeruginosa (strain EF2) was investigated by growing the organism under various conditions in batch, fed-batch and continuous culture. Lipase activity, measured as the rate of olive oil (predominantly triolein) hydrolysis, was weakly induced by general carbon and/or energy limitation, strongly induced by a wide range of fatty acyl esters including triglycerides, Spans and Tweens, and repressed by long-chain fatty acids including oleic acid. The highest lipase activities were observed during the stationary phase of batch cultures grown on Tween 80, and with Tween 80-limited fed-batch and continuous cultures grown at low specific growth rates. The lipase activity of Tween 80-limited continuous cultures was optimized with respect to pH and temperature using response surface analysis; maximum activity occurred during growth at pH 6.5, 35.5 degrees C, at a dilution rate of 0.04 h-1. Under these conditions the culture exhibited a lipase activity of 39 LU (mg cells)-1 and a specific rate of lipase production (qLipase) of 1.56 LU (mg cells)-1 h-1 (1 LU equalled 1 mumol fatty acid released min-1). Esterase activity, measured with p nitrophenyl acetate as substrate, varied approximately in parallel with lipase activity under all growth conditions, suggesting that a single enzyme may catalyse both activities. PMID- 1748875 TI - Purification and properties of extracellular lipase from Pseudomonas aeruginosa EF2. AB - Extracellular lipase was purified from a Tween 80-limited continuous culture of Pseudomonas aeruginosa EF2 by ultrafiltration of the culture supernatant followed by anion-exchange and gel-filtration FPLC. The lipase was composed of a single subunit (Mr 29,000, pI 4.9), which was capable of a variable degree of aggregation, and which exhibited both lipase activity, measured with the insoluble substrate olive oil (predominantly triolein), and esterase activity, measured with the soluble substrates p-nitrophenyl acetate and Tween 80. Lipase activity was approximately eight times higher than either type of esterase activity (kcat approximately 3000 s-1 for the hydrolysis of olive oil). The enzyme showed a marked regiospecificity for the 1,3-oleyl residues of radiolabelled triolein, was relatively stable at moderate temperatures (exhibiting a biphasic loss of activity with an initial t1/2 of 17.5 min at 60 degrees C) and was very stable to freezing and thawing. Lipase activity was only weakly inhibited by the serine-active reagent 3,4-dichloroisocoumarin, and was not inhibited by the chelating agent EDTA (1 mM). The N-terminal amino acid sequence of the Ps. aeruginosa EF2 lipase showed a marked similarity to those of several other bacterial lipases. PMID- 1748876 TI - Molecular genetics of Pseudomonas syringae pathovar pisi: plasmid involvement in cultivar-specific incompatibility. AB - A mutant (PF24) of the race 1 strain, 299A, of Pseudomonas syringae pv. pisi has been characterized in terms of its interactions with pea (Pisum sativum) cultivars. The mutant showed a changed reaction (avirulence to virulence) with a group of pea cultivars, including cvs. Belinda and Puget, previously thought to contain resistance genes R1 and R3. Avirulence towards cv. Puget was restored by transfer of any one of five cosmid clones from a race 3 (strain 870A) gene library to a rifampicin-resistant derivative of PF24. These observations were in agreement with a revised race-specific resistance genotype for Belinda and similar cultivars comprising a single resistance gene, R3. An incompatible interaction was observed between strain PF24 and cvs. Vinco (postulated to harbour race-specific resistance genes R1, R2, R3 and R5) and Hurst's Greenshaft (R4 and possibly R1), indicating that the mutant retains at least one avirulence gene (A1 or A1 and A4). Mutant PF24 showed loss of a cryptic plasmid (pAV212) compared with its progenitor, strain 299A. A subclone (pAV233) of one of the race 3 restoration clones showed strong hybridization with similar-sized digestion fragments in race 3 plasmid DNA, confirming the A3 gene to be plasmid-borne. Strong cross-hybridization was also observed with a single 3.27 kb EcoRI fragment of plasmid DNA present in strain 299A but absent from strain PF24. This is consistent with the corresponding A3 determinant being located on pAV212 in the race 1 strain 299A. The novel avirulence gene corresponding to A3 in strain 870A is provisionally designated avrPpi3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1748877 TI - A survey of peptidase activity in rumen bacteria. AB - Twenty-nine strains of 14 species of rumen bacteria were screened for their ability to hydrolyse Ala2, Ala5, GlyArg-4-methoxy-2-naphthylamide (GlyArg-MNA) and Leu-MNA. Several species, notably Megasphaera elsdenii, were active against Ala2, and a smaller number, including Bacteroides ruminicola, Butyrivibrio fibrisolvens, Ruminococcus flavefaciens, Lachnospira multipara and Ruminobacter amylophilus, broke down Ala5. Streptococcus bovis had an exceptionally high leucine arylamidase activity. However, only Ba. ruminicola hydrolysed GlyArg-MNA. Further investigation revealed that only Ba. ruminicola and Bu. fibrisolvens hydrolysed Ala5 to Ala3 and Ala2, with little ALa4 being produced, in a manner similar to rumen fluid. The activity of Ba. ruminicola against synthetic peptidase substrates, including GlyArg-MNA, LysAla-MNA, ArgArg-MNA, GlyPro-MNA, LeuVal-MNA, and Ala3-p-nitroanilide, was similar to that of rumen fluid, whereas the activity of Bu. fibrisolvens was quite different. Since the main mechanism by which peptides are broken down in the rumen is similar to dipeptidyl aminopeptidase type I, for which GlyArg-MNA is a diagnostic substrate, it was concluded that Ba. ruminicola was the most important single species in peptide breakdown in the rumen. PMID- 1748878 TI - Relationship of Wallerian degeneration to regrowing axons. AB - Because Wallerian degeneration constitutes a highly significant and unavoidable position in the sequence of nervous system regeneration we have extended our observations regarding this process as it occurs in our cryogenic model of spinal cord injury in the rat. In previous studies we have observed essentially no growth into the Wallerian zone despite a significant amount of axonal regrowth through the injured region. In the present study we have examined by electron microscopy the Wallerian degeneration and its interface with the axons from the injured region. In the Wallerian region our observations have not only confirmed those of many previous investigators but have suggested an orderly sequence of changes during the first 60 days post-injury, beginning with relative tissue preservation followed by depletion of degenerating axoplasm, extracellular deposition of myelin and the development of a cellular reaction. Associated with the cellular reaction is the development of large astrocytic cells which can be found adjacent to unmyelinated and thinly myelinated axons. With this limited evidence of support for axonal growth in the Wallerian zone it is suggested that further expansion of this cellular matrix should provide significant support to regrowing axons. PMID- 1748879 TI - Transperineurial arterioles in human sural nerve. AB - The perineurial sheath of nerve fascicles is a protective cellular layer that separates the endoneurium from the epineurium. Transperineurial arterioles (TPA) connect the endoneurial capillary plexuses to the epineurial arterial nutrient supply. Transperineurial arterioles are defined as any arteriole that is confined to a perineurial cell compartment, which would include all arterioles within the perineurium proper or within perineurial sleeves in the epi- or endoneurium. In this study of biopsied human sural nerves, three-dimensional reconstruction of one micron sections and ultrastructural analysis of step serials, we find that TPA are confined in open-ended perineurial sleeves by which they pass from the epineurium through the perineurial sheath proper into the endoneurium. Most TPA are terminal arterioles as evidenced by size (10-25 microns), morphological characteristics, and the fact that they connect with capillaries. Transperineurial arterioles gradually lose their continuous muscle coat and become post-arteriolar capillaries (PAC). Vascular segments that emerge into the endoneurium from the perineurial sleeves are generally of the PAC variety. Transperineurial arterioles and post-arteriolar capillaries are often associated with a plexus of unmyelinated nerve fibers. Axon varicosities exhibit a variety of morphologically distinct vesicles including dense-cored and a diversity of agranular vesicles. These findings suggest that TPA play a role in the neurogenic control of endoneurial blood flow. PMID- 1748880 TI - Restoration of blood-nerve barrier in neuropathy is associated with axonal regeneration and remyelination. AB - We investigated the temporal course of blood-nerve barrier (BNB) breakdown during the evolution of tellurium neuropathy, ricin neuropathy, and Wallerian degeneration following nerve transection or nerve crush. Blood-nerve barrier permeability was assessed with a 4,000-molecular weight fluoresceinated dextran from three days to 19 weeks after onset of neuropathy. Blood-nerve barrier breakdown was present during the first two weeks in all four models of neuropathy. Restoration of the BNB to the dextran began within four weeks and was complete by 14 weeks in tellurium neuropathy, a model of demyelinating neuropathy characterized by rapid remyelination, and after nerve crush, a model of Wallerian degeneration characterized by rapid axonal regeneration into distal stump. In contrast, there was persistence of BNB breakdown beyond 14 weeks in ricin neuropathy, a model of neuropathy with no axonal regeneration or remyelination, and after nerve transection, a model of Wallerian degeneration characterized by minimal axonal regeneration into distal stump. We conclude from these data that alterations in the BNB over the course of neuropathy differ among various types of neuropathy, and that these alterations are dependent on the form of nerve fiber injury. The lack of regenerating or remyelinating axons in ricin neuropathy and after nerve transection may be responsible for the persistent BNB breakdown found in these neuropathies. PMID- 1748881 TI - The neuropathologic basis of different clinical subgroups of Parkinson's disease. AB - Clinical and neuropathologic data in 45 patients with Parkinson's disease (PD) were compared. Twenty-seven patients suffered from marked akinesia and rigidity (AR-type) and 18 patients from predominant resting tremor (T-type). Dementia, depression, and psychosis occurred in 26, 18, and 18 patients, respectively. Neuronal counts were performed in defined areas of the medial and lateral substantia nigra (SNM, SNL), locus ceruleus (LC), and dorsal raphe nucleus (DRN). The AR-type (compared with the T-type) showed higher neuronal loss of LC, SNL, SNM, and more severe gliosis, extraneuronal melanin deposits, and neuroaxonal dystrophy in substantia nigra. Demented PD patients showed more intense cortical Alzheimer lesions and higher neuronal depletion in the SNM, whereas PD subjects with moderate or marked dementia differed from mildly or not demented ones only in the higher degree of cortical Alzheimer lesions. More severe neuronal cell loss of DRN was observed in PD patients with depression. Occurrence of psychosis was not associated with any pathologic feature. Our findings indicate that some major clinical features of PD are related to distinct neuropathologic lesions. PMID- 1748882 TI - Occurrence of lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 in human gliomas in vitro and in vivo. AB - Monoclonal antibodies (MAb; DMAb, monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl gangliosides 3' isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and their reactivity spectra compared to that of the alpha-3'-isoLM1 MAb SL-50. The IgM MAb SL-50 defines the epitope NeuAc (or NeuGc)alpha 2-3Gal beta 1 3GlcNAc, the terminal sequence of both gangliosides. SL-50 requires an unsubstituted GlcNAc residue; IgM DMAb-14 will accept the alpha 2-6 linked sialic acid to GlcNAc found in 3',6'-isoLD1. Immunohistochemical localization of 3' isoLM1 was performed on 31 biopsy specimens of human gliomas; 15 (48%) expressed 3'-isoLM1 as defined by binding of MAb SL-50. Staining of small anaplastic cells, giant cells, and the glial component of gliosarcomas was observed. Neoplastic gemistocytes, when present, showed particularly intense staining. The 3'-isoLM1 and 3',6'-isoLD1 distribution in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Six of 29 cell lines expressed 3'-isoLM1: 2/16 gliomas, 3/3 teratomas, 1/1 pancreatic adenocarcinoma. No cell line expressed detectable 3',6'-isoLD1 by immunostain analysis of ganglioside extracts. The 3'-iso-LM1-positive cell lines expressed it in xenograft form; in five xenografts, the corresponding cell lines of which were 3'-isoLM1-negative, it was a proportion of the monosialoganglioside fraction. 3',6'-isoLD1 was detected in two xenografts, D-54 MG (glioma) and PA-1 (teratoma). The demonstration of 3'-isoLM1 in gliomas in in vivo forms and the relatively infrequent expression by derived cultured cells suggest that ganglioside expression is modified by environmental forces. Expression of 3'-isoLM1 and 3',6' isoLD1 in fetal and neonatal brain, in intense reactive astrocytosis such as polyunsaturated fatty acid lipidosis, and in primary neoplasms of the central nervous system suggests their role in cell-cell attachment during development, migration, and neoplastic transformation. PMID- 1748883 TI - Localization of the CD44 glycoprotein to fibrous astrocytes in normal white matter and to reactive astrocytes in active lesions in multiple sclerosis. AB - The CD44 antigen is a proteoglycan recently implicated in several adhesion events including that of lymphocytes to endothelium. The CD44 antigen, reactive with monoclonal antibody (MAb) 44D10, has been shown previously to be expressed in normal human white matter homogenates and to be found at higher concentrations in brain homogenates of victims of multiple sclerosis (MS). The cellular localization of CD44 in human brain of normal individuals and in those afflicted with MS has now been determined. Monoclonal antibody 44D10 reacted with astrocyte like cells in 40 microns thick paraformaldehyde-fixed sections but not in thin (6 microns) fixed sections. A double labeling experiment performed on a frozen brain section with MAb 44D10 and rabbit anti-glial fibrillary acidic protein (GFAP), a cytoplasmic marker of astrocytes, confirmed the co-localization of these two antigens. The reactivity with brain tissue sections of a rabbit antiserum produced against lymphocyte-CD44 could be absorbed by a preparation of the CD44 glycoprotein, purified 2,100-fold from a white matter homogenate. The antiserum was shown by Western blot analysis to be specific for p80 glycoprotein in brain extracts derived from a normal and MS patients. This antibody reacted with fibrous astrocytes predominantly in white matter; staining was also noted in subependymal and subpial regions. Inhibition studies using a cellular radioimmunoassay indicated that the highest concentrations of CD44 in three MS victims were found in plaques, followed by periplaques and non-involved areas of white matter which were higher than normal white matter. Reactive astrocytes, identified in active lesions, expressed high levels of CD44 on their surfaces. Thus, CD44 is associated with astrocytes in human brain and the increased expression observed in MS brain may reflect activation and/or proliferation of astrocytes implicated in the pathogenesis of this disease. PMID- 1748884 TI - Periodontal health status and treatment needs for index age groups in Turkey based on CPITN values. AB - A national oral health pathfinder survey has been conducted by our research team in Turkey, in collaboration with the WHO European Region. Some of the data obtained by this survey were for CPITN values for age groups above 10 years, and can be summarized as follows: formula: (see text) These findings demonstrate that preventive periodontal therapy and community-based prophylaxis methods, will undoubtedly be of prime importance in future nationwide dental health service planning in Turkey. PMID- 1748885 TI - Long-term evaluation of surgical periodontal treatment with and without maintenance care. AB - A study was conducted on the effectiveness of individual maintenance recalls and the long-term effects of surgical therapy on pocket depth and tooth loss in 43 patients with moderate to advanced periodontal disease. Sixteen of the patients had periodic control and 27 were uncontrolled. Intervals of periodic recall ranged from 3 to 6 months according to individual needs. Pocket depths were measured from four aspects of each tooth and initially classified as shallow (1-3 mm), moderate (4-6 mm) or deep (7 mm or more). Changes in each pocket depth level were determined after 10 years. Tenth-year comparisons showed that the uncontrolled group had significantly higher mean pocket depth values. Tooth loss rate was 3.6% in the controlled group, and 14.1% in the uncontrolled group, and the mean numbers of lost teeth were 0.69 and 3.63, respectively, in the ten-year period. It was concluded that periodic recalls were essential for long-term success of periodontal surgery. PMID- 1748886 TI - A cephalometric study of changes in point A under the influence of upper incisor inclinations. AB - Today the ANB angle is commonly used for defining the anteroposterior apical base relationships of the jaws. The factors that influence the ANB angle have been studied by various investigators. The axial inclination of the maxillary central teeth is one of the factors influencing the location of point A. In this study the relationship between the axial inclination of the upper central incisor and the location of point A was studied. Four criteria that define the location of the maxillary central teeth were used: I (incisal point), Ap (apical point), R (rotation point), and I-SN (angle between I and SN plane). A significant positive correlation was found between the location of points A and R. We also calculated a regression equation for this relationship. PMID- 1748887 TI - Pathological study of the hyperplastic dental follicle. AB - Eleven specimens of hyperplastic dental follicles were studied clinicopathologically, with reference to the patient's sex and age at the time of diagnosis, site of the lesions, and histopathology. The patients comprised 6 males and 5 females with an average age of 15.7 years (range 10 to 23 years). Two cases involved multiple lesions, and 9 a single lesion. The lesions were related to impaction of the canine, second premolar, second molar or third molar. Radiographically, the lesions showed various degrees of radiolucency around the crown of the impacted tooth. Most of the cases were diagnosed clinically as dentigerous cyst. The histopathological features of the lesions were similar to those of normal dental follicular tissue around the developing tooth. No tumorous features such as odontogenic fibroma, odontogenic myxoma or myxofibroma were evident in the lesions. PMID- 1748888 TI - Gingival hyperplasia induced by nifedipine. AB - We describe 4 cases of gingival hyperplasia induced by nifedipine, together with clinical and histological findings. Hyperplasia of the interdental papillae was observed in all cases. Histologic examination showed multilayered epithelial parakeratosis with variations in the width, proliferation, reticulation and elongation of the rete pegs. Substitution of another drug and improvement of oral hygiene led to reduction of the gingival overgrowth without gingivectomy. These treatments are essential for gingival hyperplasia induced by nifedipine. PMID- 1748889 TI - Broadening our perspectives. PMID- 1748890 TI - Assessing career commitment. The role of staff development. AB - Staff development and inservice educators may be called on to respond to their organizations' need to recruit and retain nurses. One important role is to promote professional commitment and loyalty. This article describes the Gardner Career Commitment Scale as a tool for use in human resources management and decision making to assess career commitment. PMID- 1748891 TI - Patient controlled analgesia in pediatrics. AB - Patient controlled analgesia is a new, upcoming method of managing pain in the pediatric population. Introducing it to the nursing division of a children's hospital requires that the nursing staff development educator assess, plan, implement, and evaluate its method of introduction and use. The educator must involve multidisciplinary team members to facilitate this change. PMID- 1748892 TI - Fostering decision making in nursing. AB - Health care organizations have focused on external nursing recruitment incentives such as improved pay scales, greater bonuses, and flexible scheduling. Frequently, they have failed to take into account a fundamental source of professional satisfaction: the opportunity to make decisions. It is important for nurse managers, nurse educators, and clinical nurse specialists to understand the anatomy of the decision-making process, which includes gathering patient data, recalling possible nursing diagnoses and interventions, analyzing, synthesizing, making judgments, and implementing, following through, and evaluating the intervention. More decision making will put more fulfillment into the role of the professional nurse. PMID- 1748893 TI - Nurses' views on sexuality. Why, what, and how to change. AB - What practicing professional nurses believe about the sexual functioning of their patients has a direct influence on the patients' psychological well being. A preliminary investigation identifying some of nurses' beliefs demonstrated their attitudes and knowledge about the effects of chronic disease on sexuality. Staff development educators can assist nursing staff to change attitudes and improve knowledge through an educational program outlined in this article. PMID- 1748894 TI - Assisting nursing staff to learn and conduct research. An interinstitutional approach. AB - This article describes a resource sharing and collaborative interinstitutional project designed to assist the nursing staff of three hospitals to gain expertise in research and to promote collaborative research endeavors. Information is provided that will help staff development educators complete a similar project with a group of staff nurses. PMID- 1748895 TI - Enhancing verbal communication skills and promoting effective socialization of newly hired Spanish-speaking registered nurses. AB - Eight Spanish-speaking registered nurses from Puerto Rico were hired at the Veterans Affairs Medical Center, Washington, DC. Verbal communication with patients and staff was difficult for these highly skilled, competent nurses. This article describes a program to improve English language skills provided for the orientees. Such a program can assist staff development educators to attract well qualified, professionally satisfied staff nurses during acute shortages in hospital settings. PMID- 1748896 TI - Evaluating educational materials for patients. PMID- 1748897 TI - AIDS Train-the-Trainer Programs work. PMID- 1748898 TI - Program outcome evaluation. PMID- 1748899 TI - The fine structure of the testis, Part I. PMID- 1748900 TI - Testicular differentiation in mammals under normal and experimental conditions. AB - Gonadal differentiation begins with the establishment of a sexually undifferentiated gonad, in which gonadal cords are formed by condensation of somatic cells and deposition of basal laminar components around the cluster of epithelial-like cells. The first event of sexual differentiation is the invasion of mesenchymal and endothelial cells into the genital ridge in the XY gonad. As a consequence of this event, the gonadal cords become conspicuous, recognized as seminiferous cords (or testis cords). Cytological differentiation of Sertoli cells follows these stromal changes. In the XX gonad, by contrast, the invasion of the mesenchyme is absent and gonadal cords remain associated with the surface epithelium. In the B6.YDOM XY ovotestis, seminiferous cords and ovarian gonadal cords are often enveloped by common basal laminae, confirming that both structures share the embryonic origin. It has been recently reported that seminiferous-like cords are formed after loss of oocytes in the rat XX ovary cultured in the presence of Mullerian inhibiting substance or after long-term culture in the basic medium alone. These results are comparable with our observation on the persistent gonadal cords in the ovary of busulphan-treated rats or W/WV mutant mice, in which oogonia are absent or scarce. Ultrastructural evidence for Sertoli cell differentiation from XX cells has been presented, so far, only in the fetal mouse ovary that has been grafted beneath the kidney capsule of adult male mice. Possible mechanism of gonadal sex determination is discussed based on these morphological studies. PMID- 1748901 TI - Sertoli cells and testicular differentiation in the rat fetus. AB - The fetal testis is not merely a precursor of the adult organ: it is indeed an endocrine gland whose function is the masculinization of the fetus. It differs physiologically and morphologically from the adult testis. In this paper, the first stages of testicular differentiation in the rat are described, with special emphasis on the ultrastructural aspects. At the stage of 13.5 days after fertilization, the first Sertoli cells differentiate; they are characterized by a voluminous and little electron dense cytoplasm, a well-developed RER formed by vesicles and short cisternae filled with a flocculent material. Progressively, they polarize and adhere to one another by adherens-like junctions and cytoplasmic interdigitations to form the differentiating seminiferous cords. In the basal part of the Sertoli cells, a mat of microfilaments differentiates under the plasmalemma, while cytoplasmic blebs protruding in the extracellular space tend to disappear. A continuous basal lamina delineating the seminiferous cords begins to appear on day 14.5 and becomes widespread on day 15.5. These observations, when compared with other data from the literature, emphasize the fact that the differentiation of the Sertoli cells is the first morphological event during testicular differentiation. A possible role of the Sertoli cells in the subsequent organogenesis of the testis is suggested. PMID- 1748902 TI - High-resolution scanning electron micrographs of freeze-cracked cells in testes from normal and irradiated rats at different stages of gonadal development. AB - Newly developed techniques in high-resolution scanning electron microscopy (SEM) and for tissue-processing procedures have been applied to an investigation of structures of various cells in rat testes at different stages of gonadal maturation. A series of high-resolution SEM micrographs are presented which survey the surfaces of different types of testis cells during normal development, and which also illustrate ultrastructural features of some of their intracellular organelles. In addition, a series of high-resolution SEM micrographs are presented which compare the structural features of Sertoli cells in normal testes with those in germ-cell-depleted testes obtained from rats killed at varying times after having been irradiated in utero. We describe our observations on the structural properties of surfaces and intracellular organelles in Sertoli cells, Leydig cells, peritubular myoid cells, and some classes of germinal cells. We also consider the possible role of Sertoli cell apical cytoplasmic processes in lumen formation. Similarities are pointed out between the structure of germ-cell depleted testes, resulting from irradiation in utero, and the structure of germ cell-depleted testes in seasonal breeders during periods of involution. Finally, we discuss advantages and disadvantages of methods employed to reveal the fine structure of intracellular organelles in cells of the testis. PMID- 1748903 TI - Ultrastructure of the seminiferous epithelium and intertubular tissue of the human testis. AB - The ultrastructural features of the human testis are reviewed with emphasis upon the process of spermatogenesis and the cytology of the Leydig cells. The seminiferous epithelium is structurally partitioned by the Sertoli cells into basal and adluminal compartments via the specialized tight junctions between the Sertoli cells. Spermatogonia reside in the basal compartment, and, via a series of cell divisions, produce the primary spermatocytes, which at the commencement of their development move into the adluminal compartment, and thus the lengthy process of meiotic maturation is initiated. The fine structure of primary spermatocytes is described together with the complex transformation of the spermatids into spermatozoa during the process of spermiogenesis. Earlier studies of the organization of the human seminiferous epithelium showed that germ cells at different developmental stages formed identifiable collections termed cell associations or stages, but since several stages were seen in a single tubule cross-section, this gave the impression of an extremely irregular pattern of spermatogenic development. When the topographic arrangement of germ cells was re examined with the aid of computer modelling, a highly ordered distribution was revealed, conforming to a helical pattern based on the geometry of spirals. Thus spermatogenesis in the human testis is subjected to a precise regulation in keeping with the ordered arrangement of the germ cells seen in other mammalian species. The intertubular tissue of the human testis is composed of loose connective tissue containing blood vessels, occasional lymph capillaries, macrophages, mast cells, and the Leydig cells which occur either as single cells or form small clusters. The Leydig cell cytoplasm contains an abundant supply of smooth endoplasmic reticulum and mitochondria with tubular cristae, both features being characteristic of steroidogenic cells. Human Leydig cells contain large Reinke crystalloids of variable size and number, but their function remains obscure. The frequent occurrence of paracrystalline inclusions within the cytoplasm of the human Leydig cell suggests that these elements are precursors of the Reinke crystalloids. PMID- 1748904 TI - Ultrastructure of the aging human testis. AB - The ultrastructure of the progressive testicular involution with advancing age in men is reviewed. There is no definite age at which testicular involution begins, and the onset and severity of testicular lesions are subjected to pronounced individual variations. Hormone studies also indicate great individual variations, and subtle changes in both the testis and the pituitary develop progressively with age. Testicular size, sperm quality, and numbers of all germ cell types, Sertoli cells, and Leydig cells decrease with age. The volume occupied by the seminiferous tubules decreases, whereas that occupied by the testicular interstitium remains constant. The most frequent histological pattern of the aging testis is a mosaic of different seminiferous tubule lesions, varying from tubules with complete, although reduced, spermatogenesis, to completely sclerosed tubules. The tubules with complete spermatogenesis may show numerous morphological abnormalities in the germ cells, including multinucleation. Abnormal germ cells degenerate causing Sertoli cell vacuolation. These vacuoles correspond to dilations of the extracellular spaces resulting from the premature exfoliation of germ cells. Degenerating cells that are phagocytosed by the Sertoli cells give rise to an accumulation of lipid droplets in the Sertoli cell cytoplasm. The loss of germ cells begins with the spermatids, but progressively affects the earlier germ cell types, and tubules with maturation arrest at the level of the spermatocytes or spermatogonia are observed. The Sertoli cells show morphological abnormalities such as dedifferentiation, mitochondrial metaplasia, and multinucleation. Germ cell loss is associated with thickening of the tunica propria. When all seminiferous epithelial cells have disappeared, only an intensely collagenized tunica propria with myoid cells remains (sclerosed tubules). The Leydig cells progressively dedifferentiate with a decrease in the quantity of both smooth endoplasmic reticulum and mitochondria, together with an accumulation of lipid droplets, crystalline inclusions, and residual bodies, and formation of multinucleate cells. The development of tubular involution with age is similar to that observed after experimental ischemia, suggesting that vascular lesions may play an important role in age-related testicular atrophy. PMID- 1748905 TI - Homogeneous embedding for orientated monolayer cell cultures. PMID- 1748906 TI - Nursing observations of central venous catheters. The effect on patient outcome. AB - The purpose of this descriptive study was to obtain information concerning rates of intravascular infection in patients with central lines and to identify the variables related to nursing care of these lines that may influence the development of systemic infection. The study was conducted at a large southern teaching hospital during a 6-week period. The sample for this study consisted of adult inpatients who underwent central-line insertions. The results suggested that careful nursing observations, combined with early recognition and intervention, can significantly influence a positive patient outcome. PMID- 1748907 TI - Clinical evaluation of Per Q Cath for both pediatric and adult home infusion therapy. AB - The use of a single-lumen silastic percutaneous catheter, Per Q Cath, in home pediatric and adult cases was evaluated among 54 patients. Sixty-one catheters were successfully placed in 54 home infusion patients. No patient demonstrated systemic signs of infection or sepsis. Five catheters were removed because of local phlebitis and four because of clotting. Per Q Cath provided long-term I.V. access without the trauma and expense of inserting a central venous catheter. PMID- 1748908 TI - Lower incidence of peripheral catheter complications by the use of elastomeric hydrogel catheters in home intravenous therapy patients. AB - A prospective study was conducted to compare the performance of a nonconventional short peripheral catheter made of elastomeric hydrogel material with that of the conventional short peripheral catheters used to administer intravenous therapy to patients before this study was undertaken. The catheters were inserted in home care patients, primarily diagnosed with Lyme disease, for the delivery of I.V. antibiotic therapy. The study results showed that the institutional 48-to-72-hour removal policy for conventional catheters is not practical for the elastomeric hydrogel test catheter. However, this policy indeed appears appropriate for conventional catheters because one half (50%) of the control catheters in this study and in other published studies failed within 72 hours compared with only 19% of the test catheters. This demonstrates that catheter material significantly affects catheter performance because the nonconventional catheters could be kept in place more than twice as long before causing the complication rates seen with the conventional control catheters at 3 days of dwell. PMID- 1748909 TI - Thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder that was considered a fatal disease until the early 1960s. This syndrome is complex and controversial. It has been characterized by thrombocytopenic purpura, hemolytic anemia, neurologic symptoms, renal disease, and fever. The causative factor appears to be an increase of a platelet-aggregating factor or a deficiency in some platelet-aggregation inhibitor. The disease process seen is usually caused by endothelial damage mediated by a variety of stimuli. This endothelial damage then results in the formation of microscopic thrombi composed primarily of platelets and found in the small blood vessels of many organs. TTP can occur in any age group but is most often seen in patients 30 to 50 years of age. It is a very serious and potentially fatal acute disorder, but greater than 50% of the patients with this syndrome will have long-lasting remission if proper therapy is initiated and maintained. This article presents clinical findings and symptoms, methods of diagnosis, and appropriate therapeutic interventions for this disorder. PMID- 1748910 TI - State boards of nursing and issues of advanced practice. AB - Technological advances in today's health care arena and the evolution of the nursing profession have resulted in many questions about scope-of-practice issues. These questions are of a legal nature and frequently must be addressed by the board of nursing in each state. The results of a survey of all state boards of nursing are discussed along with recommendations for the preparation needed to approach a state board of nursing. PMID- 1748911 TI - Recent comparison of catheters makes unsubstantiated conclusions. PMID- 1748912 TI - A comparative study--manual versus computerized automated drug delivery systems. AB - In this study, single-channel manual pumps were compared with multiple-channel computerized pumps with respect to specific nursing and pharmacy procedures. The nursing procedures include all the steps involved in taking care of a central line catheter, from verifying physician's orders, performing line changes, administering intermittent medications, and documenting fluids and medication infusions. The pharmacy procedures included assembling and priming the infusion sets. Nurses and pharmacy technicians were observed performing these functions, and a total of 358 timed observations were obtained. The data revealed a greater time savings with the computerized multiple-channel system when complex intravenous therapy is necessary. PMID- 1748913 TI - Filtering out the confusion about leukocyte-poor blood components. AB - During the past decade, intensive investigation into the adverse clinical potential of leukocytes in red cell and platelet products has been undertaken. Clinical data indicated several benefits associated with the delivery of leukocyte-depleted blood products. These benefits include a reduction in nonhemolytic febrile transfusion reactions, human leukocyte antigen alloimmunization, and viral transmission. In response to such findings, several procedures and devices have been designed to remove leukocytes from blood components. PMID- 1748914 TI - Nursing perspectives on intraperitoneal chemotherapy. AB - During the past decade, a number of studies have established that there is a considerable pharmacologic advantage to direct intraperitoneal instillation of chemotherapy for treatment of cancer confined to the abdominal cavity. This article explores the history, present status, and future directions of intraperitoneal chemotherapy. The therapeutic advantages, various chemotherapeutic agents used, delivery systems, administration procedures, toxic effects, and nursing management are addressed. PMID- 1748915 TI - The immune system and intravenous administration of immune globulin. Part I, The immune system. AB - Interest in the immune response has greatly increased, mostly because of the discovery of the AIDS virus. An understanding of the basic function of the normal human immune system is vital knowledge for today's nurse. Part 1 of this article describes normal immune response as well as abnormal immune system function, and correlates this information with the clinical picture of the patient. PMID- 1748916 TI - Bar code systems justify staffing for i.v. teams. AB - This article concerns the implementation of a bar code system in an i.v. department. The i.v. team was disbanded in 1984 and 1985. The team was brought back, but it was a struggle to maintain staff and deliver quality, comprehensive i.v. services. With the implementation of the bar code system, nursing productivity could be demonstrated. The i.v. department now generates revenue of significant magnitude, and productivity can be proved with the new bar code system. PMID- 1748917 TI - The benefits of professional credentialing. PMID- 1748918 TI - Provision of intravenous therapy in a skilled nursing facility. AB - Intravenous therapy is one of the admission criteria for the geriatric patient to enter a skilled nursing facility. Because of shortened hospital stays, more and more geriatric patients are placed in this type of nursing home. These facilities are also potential alternatives to hospitalization of the nursing home resident who requires I.V. therapy. Multiple factors, such as the aging population, federal programs for the elderly, and the economic health care climate, have contributed to the emergence of the skilled nursing facility as a practice setting for I.V. therapy. As the acuity of nursing home residents continues to rise, I.V. therapy will become a more frequent treatment modality. Therefore, I.V. nurses must be aware of the impact of provision of this service in the skilled nursing facility setting. PMID- 1748919 TI - All about patient-controlled analgesia. AB - The goal of patient-controlled analgesia is to provide the patient with a serum analgesia level for comfort with minimal sedation. In light of the increased use of patient-controlled analgesia, this article details indications for the administration of pain control as well as available technology and monitoring parameters within the hospital and home care environment. PMID- 1748920 TI - Future dimensions in vascular access--peripheral implantable ports. AB - The development of reliable long-term intravenous access devices is both a blessing for patients and a challenge for nurses. The peripheral implantable port is a unique vascular access device that offers some new advantages over previously developed central venous catheters. This article includes a brief review of prior advances in vascular access, as well as indications, insertion techniques, advantages, disadvantages, and nursing management of the new peripheral implantable port (Port-A-Cath P.A.S. Port, Pharmacia Deltec Inc., St. Paul, Minn.). Additionally, a retrospective study of clinical experience and complications is presented. PMID- 1748921 TI - The immune system. Part II, Intravenous administration of immune globulin. AB - Part I of this article, published in the September/October 1991 issue of the Journal of Intravenous Nursing, reviews normal immune function, immune disorders, and diagnosis. The main treatment modality discussed in Part II is therapy with immune globulin IgG. History, indications, administration technique, and nursing care are highlighted. PMID- 1748922 TI - Immune function and nutrition. The clinical role of the intravenous nurse. AB - Protein-calorie malnutrition is considered to be one of the most frequent causes of immunosuppression in the world today. Malnutrition can affect the functioning of T cells, B cells, and macrophages, the principle players involved in cell mediated and humoral immunity. Immune function is measured by the total lymphocyte count and delayed cutaneous hypersensitivity reaction. Nutritional markers include serum albumin and transferrin levels. Immune function is affected by protein (especially arginine intake); the balance between omega-6 and omega-3 fatty acid intake; and adequate amounts of vitamins A, E, and C, and the minerals zinc and iron. A deficiency of these nutrients puts the patient at increased risk of infection. Non-nutritional factors can influence immune functioning as well. The intravenous nurse must review the patients history, physical examination, and laboratory values to achieve a global view of the patient's immune function and nutrition status in order to be able to develop an appropriate care plan based on this nursing diagnosis: potential for infection secondary to alteration in immune function. PMID- 1748923 TI - Homicide: a killer of youth. PMID- 1748924 TI - Pediatric nurse practitioners: primary care providers and case managers for chronically ill children at home. AB - A new role has been developed for pediatric nurse practitioners that is home based and provides primary care and case management for chronically ill children. In a pilot program at Children's Hospital and Health Center in San Diego, pediatric nurse practitioners address the complex needs of chronically ill children who require comprehensive care, education, psychosocial support, and coordination of services. This article describes the population, program, and expanded role for PNPs, emphasizing case management, management of chronic illness, minor illnesses, and management of well child care. Clinical impressions of the benefits of the role to the child and family are presented. PMID- 1748925 TI - Childrearing knowledge, beliefs, and practices of Cambodian refugees. AB - Forty Cambodian women in Seattle, Washington were interviewed to learn about their childrearing knowledge, beliefs, practices, and information resources. It was found that women who once relied on family and elders for advice now turned to pediatric providers and other clinic staff. Most women reported accurately the ages at which developmental milestones occur, with the exception of vision and hearing milestones. Their treatment of common childhood illnesses included both Western and Cambodian remedies. Beliefs about children's nature, discipline, learning, and reincarnation were explored. Implications for providers trying to support the parenting efforts of Cambodian women in the United States are discussed. PMID- 1748926 TI - Physiologic sequelae of prematurity: the nurse practitioner's role. Part VI. Feeding difficulties and growth failure. (Prevention, intervention, parent teaching, and complications). AB - Feeding difficulties and growth failure are common problems of the premature infant who has been in a neonatal intensive care unit. This article, the sixth in a series, discusses the prevention, intervention, and parent teaching necessary to assist parents in coping and dealing with feeding problems in their premature infant. PMID- 1748927 TI - Vesicoureteral reflux. AB - Vesicoureteral reflux, the regurgitation of urine from the bladder into the ureters, varies in severity. Controversy persists in relation to the cause, diagnosis, significance, and treatment of this condition. The practitioner's role in early referral and treatment of urinary tract infection is important to prevent renal damage. Patient and family support and education about reflux, diagnosis, and follow-up is crucial. Early diagnosis and optimal management will preserve maximal renal function, and patient education will foster compliance and quality care. PMID- 1748928 TI - The future of cocaine babies: primary care and early intervention. PMID- 1748929 TI - Moral development. PMID- 1748930 TI - Growth hormone therapy for short stature. PMID- 1748931 TI - Abdominal mass on a well child examination. PMID- 1748932 TI - New pesticide policies focus on pediatrics. PMID- 1748933 TI - New role for PNPs in an inpatient setting. PMID- 1748934 TI - Association of Faculties of Pediatric Nurse Practitioner/Associates Programs. Update. PMID- 1748935 TI - NAPNAP position statements. PMID- 1748936 TI - Transvaginal color Doppler in the assessment of abnormal early pregnancy. AB - The study groups comprised 61 pregnant women whose gestational age ranged from 7 to 12 weeks from the last menstrual period. All patients apparently had a normal developing pregnancy; there were no clinical symptoms of pathology e.g. bleeding in early pregnancy. Eighty-two patients with a clinically and ultrasonographically normal pregnancy whose gestational age ranged from 7 to 12 weeks, served as a control group. When the anatomical position of investigated area have been obtained clearly, pulsed wave Doppler sample volume was placed on the structures of interest: the both uterine arteries and intervillous space. There is no statistically significant difference between the Resistance Index (RI) in the left or right uterine artery (P greater than 0.01) and among investigated groups of patients (P greater than 0.01). The intervillous blood flow RI in the case of molar pregnancy was 0.38 with SD +/- 0.03; in blighted ovum 0.43 with SD +/- 0.03, and in missed abortion 0.43 with SD +/- 0.02. It should be stressed that in nine (31%) cases of blighted ova and in five (26%) cases of missed abortion, intervillous space flow could not be detected. In the control group, intervillous blood flow was always visualized and the mean RI was 0.45 with SD - 0.04. Statistical analysis showed significantly higher RI in control group in comparison with other groups of patients (P less than 0.01), and significantly lower RI in molar pregnancy in comparison with other groups of patients (P less than 0.01). There was no difference in RI between blighted ova and missed abortions (P greater than 0.01). PMID- 1748937 TI - Single dose of labetalol in hypertensive pregnancy: effects on maternal hemodynamics and uterine and fetal flow velocity waveforms. AB - The short-term effect of 0.8 mg/kg of an intravenous bolus of labetalol on maternal and fetal hemodynamics was investigated in ten women with pregnancy induced hypertension. The maximum effect occurred within 35 minutes after labetalol administration. At that point, the mean arterial pressure had decreased by 18% and there was a slight decrease in maternal heart rate. As to flow velocity waveforms, no significant change was found in mean systolic/diastolic (S/D) ratio of the uterine artery, umbilical artery or fetal middle cerebral artery. However, in two subjects with a marked reduction in blood pressure also the uterine artery S/D ratio decreased. PMID- 1748938 TI - Indomethacin therapy and fetal urine production in twins with polyhydramnios. AB - Indomethacin has been used in twins with polyhydramnios to decrease amniotic fluid volume. Under therapy, a marked reduction of both fetuses' urine production has been demonstrated within 24 hours concomitant with maternal symptomatic relief. Discontinuation of therapy was associated with a rapid increase in fetal urine production. The clinical observation indicates that the benefit of indomethacin in prolonging such pregnancies is most probably the result of relief of polyhydramnios through decreased fetal urine production. PMID- 1748939 TI - Auditory evoked response of the human fetus: simplified methodology. AB - The author presents a retrospective study where he analyzes the possibility of using sound-evoked movements of human fetuses to evaluate their conditions in utero. He uses a narrow band stimulator at 1,500 cycles/second at 125 decibels of sound level pressure as five pulsed stimuli lasting two seconds each and one second apart applied to maternal abdomen. Analysis was performed on 2,025 fetal electronic monitoring tests on which 1,626 auditive stimulation were applied. A test was considered positive when sound stimulation evoked no movements or only a slight, slow, not immediate movement was observed by the mother or the professional applying the test. A test was considered negative (fetus in good health) when a fetal immediate sudden, strong, Moro like reaction was observed clinically (starttle reflex). This test produced a sensitivity of 57.35%, greater than any other observed in nonstress cardiotocography. The author suggests this simple, easy-to-apply test should have a place as screening procedure in large populations or where facilities for more complete monitoring are not available. The combination of this simplified auditive stimulation with the conventional auditory evoked response offers better sensitivity and positive predictive values than the largely used non-stress test. In any case it would help in the detection of potential risk cases and should be included as a first simple procedure to be applied to high risk pregnancies. PMID- 1748940 TI - The effect of maternal oxygen administration on fetal and maternal blood flow values using Doppler ultrasonography. AB - Thirty-one pregnant women divided into three groups (AGA prepartum, SGA prepartum without distress, AGA in labor) were examined using Doppler ultrasonography before, during and after oxygen administration to mothers via a face mask. The aim of the study was to find out if there was any effect on the blood flow values in the fetal aorta, the umbilical artery, the fetal common carotid artery and the uterine arcuate arteries. The resistance index (RI) did not change in those vessels during maternal hyperoxygenation with one exception: in the group of SGA fetuses the RI in the fetal aorta increased significantly. Blood flow velocity and volume blood flow remained unchanged in the fetal aorta during oxygen administration. PMID- 1748941 TI - Significance of prenatal diagnosis in a patient with a huge neck tumor. AB - Due to the great advancements in fetal ultrasonography, the number of prenatal diagnoses are increasing, greatly contributing to improved neonatal surgery. It is now relatively easy to detect huge fetal cystic masses, and we have experienced three cases with a huge neck tumor detected in utero, one case with teratoma and two cases with cystic hygroma. Each case was complicated by neonatal asphyxia, and the neonate needed resuscitation by means of endotracheal intubation. The infant with teratoma unfortunately died of respiratory distress due to compression of the trachea before a perinatal team could be organized. Although the remaining cases with cystic hygroma were treated by a perinatal team, one died 19 hours after birth and the other has survived with the aid of endotracheal intubation in the hospital for three years. In addition, all four cases of cystic hygroma detected antenatally in our institute, which were not delivered, also had fetal hydrops which suggested a general lymphatic derangement. Cystic hygroma detected in utero is considered to be different from that detected after birth, since the former is associated with genetic lymphatic derangement. Prenatal diagnosis enables such patients to survive the perinatal period, but may not improve the prognosis of fetal cystic hygroma so much. PMID- 1748942 TI - Pressures on the fetal head during normal labor. AB - The pressure recordings from both parietal regions of the fetal head during the second stage of labor of 44 spontaneous deliveries with vertex presentation were evaluated and compared to the simultaneously recorded pressures in the amniotic cavity by calculating pressure parameters during and between uterine contractions. Analysis of the bearing down period revealed on the average higher values at the anterior side in comparison to the posterior side of the skull. This is explained by the complex anatomy of the curved birth canal. Overall, the head pressure values averaged from the recordings of both parietal regions were about twice as high as the corresponding amniotic pressure values. During the descend of the head through the birth canal, an increase of pressure on the fetal head was observed that is mainly due to the rising resistance of the narrowing pelvis and stretched tissue of the passageway. A marked interindividual deviation of head pressure was found that was independent from amniotic pressure variations thus preventing indirect deduction of head strain from internal togography. PMID- 1748943 TI - Predictive value of a fetal heart rate acceleration at the time of fetal blood sampling in labour. AB - It has been suggested that the fetal heart rate response to fetal stimulation in labour is an indication of fetal condition. This study was designed to evaluate scalp stimulation at the time of fetal blood sampling. All labours requiring fetal scalp pH measurement during one year at the John Radcliffe Maternity Hospital were reviewed to determine the association between pH result and the fetal heart rate response to the first scalp blood sample. Sixty-nine (50%) cases showed an acceleration and none had a scalp blood pH less than 7.20. Six (8.7%) of the cases which did not show an acceleration of the fetal heart rate had a pH less than 7.20 and this group had a greater incidence of analgesia usage and twice as many caesarean sections (39%). The detection rate for non-acidaemia using a fetal heart rate acceleration at the time of fetal blood sampling was 52 percent but the specificity and positive predictive value were both 100 percent. The false negative rate was 91 percent. Thus, whilst an acceleration was reassuring, the absence of an acceleration at the time of fetal blood sampling was not a good predictor of fetal acidaemia. These results are compared with the data from four other published reports. PMID- 1748944 TI - Scalp electrode associated neonatal Escherichia coli meningitis--a case report. AB - A case of Escherichia coli meningitis in a newborn boy is described which seemed to be related to the use of a screwed top scalp electrode for perinatal monitoring. First a subcutaneous abscess developed at the place of the former electrode and the infant recovered well after surgical incision. 36 hour later the boy became acutely ill because of a purulent meningitis. From both the subcutaneous Abscess as the CSF identical E. coli (K1-strain) were cultured. PMID- 1748945 TI - How to assess fetal metabolic acidosis from cord samples. AB - The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis. PMID- 1748946 TI - Prenatal diagnosis of vein of Galen arteriovenous malformation by duplex sonography. AB - Arteriovenous malformation of the vein of Galen, a rare disorder, has been diagnosed in several cases by in utero sonography. A case is presented in which the prenatal diagnosis of this entity was made by the combined use of real-time ultrasound and pulsed Doppler. PMID- 1748947 TI - Endoscopic fetal surgery by excimer laser. An experimental study in premature lambs. AB - Fetal malformations are detected early in pregnancy by means of ultrasound challenging fetal therapy. While open fetal surgery has been preformed during preliminary clinical trials we evaluated fetoscopic therapy avoiding laparotomy and uterotomy. We used a laser fibre (900 mu) which was introduced into the uterus by an endoscope. During animal experiments in five fetal lambs with a gestational age of 120-122 days we used an excimer laser (Technolas, x) with a wave-length of 308 nm. Laser incisions were compared with the conventional cutting technique using a scapel. During histological evaluation the tissue effect was morphometricly analysed. The zone of devitalisation was characterized by pycnosis of the nuclei and in a change of cytoplasma volume. The excimer laser incisions using a frequency of 40 HZ had a mean zone of devitalisation of 50.3 +/ 4.5 mu. Using the excimer laser with a frequency of 10 HZ we found a tissue alteration of only 11.2 +/- 3.4 mu. The incisions by scapel showed a extended traumatisation with a mean tissue effect of 153.2 +/- 16.3 mu. From these results we conclude, that endoscopic surgery may be come a usefull additional tool for fetal therapy. PMID- 1748948 TI - School-based adolescent mental health project survey of depression, suicidal ideation, and anger. AB - This study on adolescent mental health was conducted in a school setting. Sixty nine subjects, aged 16-18 years, were surveyed to provide data on anger, depression, and suicide ideation. Suicide ideation was present in 15.9% of subjects and depression in 14.1%. Subjects with suicidal ideation demonstrated greater levels of anger and pooer anger control. Recommendations are made for psychiatric nurses to collaborate with school administrators to develop programs with specific evaluation criteria to promote adolescent mental health in the schools. PMID- 1748949 TI - Exploring the grief of adolescents after the death of a parent. AB - This study explored the grief of 26 adolescents after the death of a parent during the subjects' adolescent years. Data collection involved a one-time semi structured interview. In addition, the adolescents were asked to write and draw about death. The study identified variables and themes that appeared to have possible significance for how adolescents coped. The study conclusions were that adolescents do grieve differently from children and differently from adults; younger adolescents even grieve differently from older adolescents. No discernible differences in grieving were ascertained on the basis of sex, type of death, or prior loss experiences. The one adolescent who was perceived as grieving in an adaptive manner had the advantage of open communication with family members, had closure with the parent now dead, had seen the parent when dead, and had been involved with the rituals surrounding the death. Implications for future research and recommendations for adults involved with adolescents are included. PMID- 1748950 TI - Intuition in psychiatric-mental health nursing. AB - A descriptive study was done to explore how psychiatric-mental health nurses define and act on intuition in clinical practice with children and adolescents, and to identify supports for and barriers to taking such action. Interviews of 16 nurses were tape-recorded, transcribed, and analyzed for manifest and latent content. Findings support previous studies about intuition in nursing practice and have implications for psychiatric-mental health nurses working with high-risk populations of children and adolescents. PMID- 1748951 TI - Infant-toddler mental health. An emerging concern. PMID- 1748952 TI - Communication techniques for allaying anxiety and providing support for hospitalized children. PMID- 1748953 TI - Perceived stress and stress projected into the spontaneous storytelling of two groups of fourth grade children. AB - The purpose of this descriptive correlation study was to describe stress levels in fourth grade children from two geographic locations: an inner city recreation club and a suburban parochial school. The use of spontaneous storytelling and a life events questionnaire provided information about the stress being experienced by the children. This article presents story themes and stressful life events of interest to adult caregivers helping children cope with stressful experiences. PMID- 1748954 TI - Marital strife, social support, and the development of mentally retarded toddlers. AB - The birth of a mentally retarded child is a stressful experience for the family. Research exploring the differences between these families based on the child's developmental competence is sparse. This study examined marital strife and social support within two groups of retarded toddlers. Data were collected through observation, an interview, and questionnaires. The focus of marital agreement and disagreement differed between the groups, as did social support. However, birth order and family life cycle stage were found to be important confounding variables. PMID- 1748955 TI - Evaluation of a teen parent program designed to reduce child abuse and neglect and to strengthen families. AB - The purpose of this study was to evaluate a teen parent program designed to increase parents' self-esteem, improve parenting skills, and increase parental knowledge about child development. Subjects (n = 30) in the program were referred from public health services. Control subjects (n = 30) were served by a local health department. Subjects were tested before and on completion of the program (or 6-9 months later for controls) using the Coopersmith Self-Esteem Inventory (SEI), the Inventory of Parents' Experiences (IPE), and the Denver Developmental Screening Test (DDST). Findings included (a) intervention subjects scored lower than control subjects on the pretesting in self-esteem (p less than 0.05), parental role satisfaction (p less than 0.05), and community support (p less than 0.0001); (b) control subjects scored lower on satisfaction with intimate relationships (p less than 0.0001); (c) at post-test, there were no statistically significant differences, and intervention subjects recorded self-esteem scores had increased to control levels; and (d) no developmental delays were detected in newborns at either pre- or post-testing. Implications of this study include (a) data support effectiveness of the program in enhancing self-esteem, maintaining satisfaction in parental role, and increasing community support for teen parents; and (b) evaluation of teen parent programs' effects should be done every 3-6 months to reduce subject attrition. PMID- 1748956 TI - Assessing psychotropic medication side effects among children. A reliability study. AB - The Dosage Record Treatment Emergent Symptom Scale (DOTES) is a rating scale for measuring the presence and intensity of psychotropic medication side effects. Studies to evaluate its reliability have not been published. The purposes of this pilot study are to (1) develop a protocol for training raters to use the DOTES, (2) assess inter-rater agreement, 3) examine the reasons for disagreement among raters to clarify training procedures and symptom definitions, and (4) further refine this instrument for use in clinical and research settings. Five nurses were trained to use the DOTES to rate the absence or presence and intensity of specific medication side effects. After training, Raters 1, 2, and 3 watched a videotape of a nurse interviewing a 13-year-old child and completed the DOTES rating scale. There was agreement on the intensities of 6 (67%) of the 9 symptoms identified as present and agreement on 17 (89%) of the 19 symptoms identified as absent. Process tracings were conducted on the ratings of Nurses 4 and 5 to elicit the criteria they used to determine their ratings. The results of the process tracings were used to identify ambiguities that led to disagreement among raters so that the training protocol and interview could be improved. PMID- 1748957 TI - HIV infection. Helping adolescents choose safer behaviors. AB - Although adolescents comprise only 1% of the diagnosed cases of acquired immune deficiency syndrome (AIDS), the risk of human immunodeficiency virus (HIV) infection among this group should not be underestimated. This article discusses how adolescents' behaviors place them at risk for HIV infection. One educational program is described that illustrates an innovative approach to use with adolescents. Nurses who use the Relationship Safety and Vigilance Plan can assist individual adolescents to assess their interpersonal relationship patterns to establish goals and reduce impulsive or destructive behaviors. PMID- 1748958 TI - Perceived seriousness of children's surgery and family adaptability and cohesion. AB - This study investigates the relationship between the family's perception of the seriousness of a child's surgery and the level of family adaptability and cohesion before and after the surgical event. Research hypotheses are based on the Family Crisis and Circumplex models of marital and family systems. Forty-one families were included in the pretest/posttest single group design in which a child underwent a tonsillectomy. Study findings do not consistently support the conceptual models, and implications for the testing of middle range family theories are described. PMID- 1748959 TI - Development of an adolescent risk-taking instrument. AB - The purpose of this research study was to estimate the reliability and content validity of an instrument designed to measure risk-taking in adolescents. Six subscales containing 69 items were developed to measure the adolescent's perception of risk-taking. Subjects consisted of 75 male and female adolescents enrolled in a vocational training program. Support for reliability was obtained by the use of Chronbach's alpha correlation coefficient for the subscales and the Risk-Taking Instrument. PMID- 1748960 TI - Genetic epidemiology in child psychiatric nursing. Tourette's Syndrome as a model. AB - Recent discoveries in the field of molecular biology and increased attention to genetic epidemiology have stimulated renewed interest in the genetics of psychiatric disorders. Tourette's syndrome, a neuropsychiatric disorder characterized by motor and phonic tics, is used as a model to describe the research strategies employed in the genetic epidemiology of child psychiatric disorders. The relevance of genetic research findings to child psychiatric nursing is also discussed. PMID- 1748961 TI - An electrodynographic study of foot function in shoes of varying heel heights. AB - Forty-three female test subjects had electrodynographic gait analysis performed in barefoot, low-heel shoe, and high-heel shoe conditions. Comparisons of segmental foot function, actual pressures, and pressure durations were determined. The findings suggest that an increased duration of forefoot loading, rather than an increased actual pressure, is responsible for pedal pathology secondary to wearing high-heel shoes. Contrary to previous reports in the literature, evidence of abnormal pronation in high heels was not found in this study. PMID- 1748962 TI - Isolation of a stimulatory system in an Aloe extract. AB - The authors' previous work on a 50% ethanol extract of Aloe vera was done to evaluate anti-inflammatory activity using the croton oil-induced ear swelling assay. The anti-inflammatory activity was found in the supernatant fraction. The supernatant fraction decreased inflammation, when applied topically, by 29.2%, and the precipitate decreased inflammation by 12.1%. However, in the present work, the precipitate fraction decreased the wound diameter by an average of 47.1% (stimulatory system). Little or no wound healing activity was found in the supernatant. Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions. PMID- 1748963 TI - Anterior inferior tibiofibular ligament. Variations and relationship to the talus. AB - The anterior inferior tibiofibular ligament was evaluated in 46 preserved specimens with a mean age of 73.8 years. A classification system was devised to encompass the observed variations in ligamentous structure. Particular emphasis was placed on evaluating the extent of impingement between the inferior border of the ligament and the talus. It was determined that the presence of a separate inferior fascicle is not a prerequisite for impingement. However, a triangular, beveled region located anteriorly on the border between the trochlear and lateral surfaces of the talus was identified in association with anterior inferior tibiofibular ligament impingement. PMID- 1748964 TI - Achilles tendon rupture. A protocol for conservative management. AB - The authors discuss surgical versus conservative management of closed Achilles tendon ruptures. They favor a conservative approach in most cases and present arguments to support this preference. They present a protocol for conservative management of closed Achilles tendon ruptures, which has been developed at the Center for Sports Medicine, Saint Francis Memorial Hospital, San Francisco. PMID- 1748965 TI - Charcot-Marie-Tooth disease. Podiatric and systemic considerations. AB - Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy with well documented manifestations in the extremities. Recent literature suggests systemic involvement in this neuropathy. The authors present a review of the literature, anesthetic considerations, and practical recommendations for the assessment of involved systems. PMID- 1748966 TI - Fracture-dislocation of the talus in the pediatric patient. An unusual injury. AB - Subtalar fracture-dislocations in children are unusual, perhaps because of the greater elasticity of bone in children. The authors have presented a case of medial subtalar dislocation in a 13-year-old boy, accompanied by a rare fracture of the entire posterior process of the talus. This particular fracture has not been previously reported in association with a subtalar joint dislocation, nor has it been reported in a child. The patient was treated successfully by closed reduction of both the dislocation and the fractures. PMID- 1748967 TI - Bilateral styloid fracture. A case report. AB - Styloid fractures are common, and their treatment is relatively straightforward. This case demonstrated delayed healing because of continuous pathologic motion aggravating the styloid fractures. PMID- 1748968 TI - Intraosseous lipoma of the calcaneus. A case report. AB - The intention of this report is to heighten the practitioner's clinical suspicion of intraosseous lipoma of the calcaneus. The apparent infrequency of this diagnosis may be attributed to the dependence on radiographic evaluation and the use of closed needle biopsy. Thus, to make a proper diagnosis, a computed tomography scan with the rate of attenuation and, ultimately, a large tissue biopsy with attentive gross and microscopic examination are necessary. PMID- 1748969 TI - Middle facet talocalcaneal coalition presenting with a subtalar varus deformity. PMID- 1748970 TI - The stepped cuboid. AB - The authors review a case presentation of a symptomatic cuboid metatarsal joint anomaly and discuss possible treatments, both conservative and surgical. The patient was treated conservatively and had some relief of symptoms. PMID- 1748971 TI - Physicians' plan for health care reform. AB - Numerous proposals have been made for health care reform during the last decade. Still, the richest health care system in the world offers little or nothing to millions of Americans. The quality of nursing practice is threatened by calls for rationing of health care resources and cost control. The Canadian system for national health care is frequently cited as a model for health care reform in the United States. Physicians for a National Health Program have designed a plan similar to that of Canada. This article presents an overview of the physicians' proposal and suggests its comparison with that of the Pepper Commission. PMID- 1748972 TI - In the line of duty. PMID- 1748973 TI - The coding of signals in the electric communication of the gymnotiform fish Eigenmannia: from electroreceptors to neurons in the torus semicircularis of the midbrain. AB - In the context of aggression and courtship, Eigenmannia repeatedly interrupts its electric organ discharges (EODs) These interruptions contain low-frequency components as well as high-frequency transients and, therefore, stimulate ampullary and tuberous electroreceptors, respectively. Information provided by these two classes of receptors is relayed along separate pathways, via the electrosensory lateral line lobe (ELL) of the hindbrain, to the dorsal torus semicircularis (TSd) of the midbrain. Some neurons of the torus receive inputs from both types of receptors and some respond predominantly to EOD interruptions while being rather insensitive to other forms of signal modulations. This high selectivity appears to result from convergence and gating of inputs from individually less selective neurons. PMID- 1748974 TI - Directional hearing in the gray tree frog Hyla versicolor: eardrum vibrations and phonotaxis. AB - 1. We used laser vibrometry to study the vibrational frequency response of the eardrum of female gray tree frogs for different positions of the sound source in three-dimensional space. Furthermore, we studied the accuracy of 3-D phonotaxis in the same species for sounds with different frequency contents. 2. The directionality of the eardrum was most pronounced in a narrow frequency range between 1.3 and 1.8 kHz. 3. The average 3-D, horizontal and vertical jump error angles for phonotactic approaches with a sound similar to the natural advertisement call (1.1 and 2.2 kHz frequency components) were 23 degrees, 19 degrees and 12 degrees, respectively. 4. 3-D jump error angle distributions for the 1.4 + 2.2 kHz, 1.0 kHz and 2.0 kHz sounds were not significantly different from that for the 1.1 + 2.2 kHz sound. 5. The average 3-D jump error angle for the 1.4 kHz sound was 36 degrees, and the distribution was significantly different from that for the 1.1 + 2.2 kHz sound. Hence, phonotactic accuracy was poorer in the frequency range of maximum eardrum directionality. 6. Head scanning was not observed and is apparently unnecessary for accurate sound localization in three-dimensional space. 7. Changes in overall sound pressure level experienced by the frog during phonotactic approaches are not an important cue for sound localization. PMID- 1748975 TI - Expression of circadian rhythmicity in Djungarian hamsters under constant light: effects of light intensity and the circadian system's state. AB - Djungarian hamsters (Phodopus sungorus), were exposed to constant light with increasing intensities (20, 60, 350 lux), and wheel running activity was recorded. With increasing light intensity the percentage of hamsters showing a split in their daily activity pattern increased and the free running period was lengthened for both the unsplit and the split state. The fact that the free running period of both states depended on the light intensity together with the observation that the highest incidence of a circadian activity occurred under 350 lux, provoked the idea that the emergence of splitting or a circadian rhythmicity is a direct consequence of the light induced lengthening of the free running period. However, analysis of the data failed to support the idea that emergence of a split or a circadian activity is a threshold phenomenon with respect to the free running period. Due to differences in circadian function some Djungarian hamsters do not exhibit photoinduction following short day exposure. In these individuals splitting also occurred but required exposure to a higher light intensity than in photo-responsive hamsters. This observation is in accordance with the idea that the two phenotypes differ in the interaction of the two component oscillators underlying circadian rhythmicity. PMID- 1748976 TI - Seismic and auditory tuning curves from bullfrog saccular and amphibian papillar axons. AB - We present seismic and auditory frequency tuning curves of individual bullfrog, Rana catesbeiana, saccular and amphibian papilla axons that responded to both seismic and auditory stimuli. In this study we found: 1) most saccular axons respond well to auditory stimuli with moderate signal strength (50-70 dB SPL) as well as to seismic stimuli; 2) most amphibian papilla axons respond well to seismic stimuli as well as to auditory stimuli, and their seismic sensitivities are comparable to those of saccular axons (responding to sinusoidal stimuli with peak accelerations in the range 0.001 to 0.1 cm/S2); 3) the responses to both seismic and auditory stimuli from both saccule and amphibian papilla are tuned, i.e. the strength of the response varies with the frequency of the stimulus; and this tuning is clearly not the result of second order resonance; 4) in individual axons the tuning properties for seismic stimuli often are not the same as those for auditory stimuli, a fact that may provide clues about how the stimulus signal energy is transferred to the hair cells in each case. PMID- 1748977 TI - Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma. AB - Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol. PMID- 1748979 TI - Prognostic factors in dogs with lymphoma and associated hypercalcemia. AB - Lymphoma and hypercalcemia were diagnosed in 37 dogs. Twenty-six of the dogs received chemotherapy. The association between some prognostic factors including clinical stage of disease, illness status, presence of bone marrow involvement, and presence of an anterior mediastinal mass and remission duration and survival time was evaluated. Statistical analysis of the prognostic factors showed that the presence of an anterior mediastinal mass had an adverse effect on remission duration (P less than 0.03). Calcium concentration was not significantly related to any of the prognostic factors evaluated. Dogs that received chemotherapy were more likely to be self-supporting than the dogs that were not treated (P less than 0.005). However, initial illness status was not significantly related to remission duration or survival time in the 26 dogs that were treated. Six dogs (25% of dogs treated) survived longer than 14 months. Five of these dogs were female. Overall mean and median remission times were 10.4 and 6 months, respectively. PMID- 1748978 TI - Unusual patterns of serum antibodies to Streptococcus equi in two horses with purpura hemorrhagica. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for use in horses to determine serum titers of antibodies of the immunoglobulin classes IgA, IgG, and IgM to Streptococcus equi M-like protein and culture supernatant protein antigens. Serum antibodies were determined in 28 adult horses, including 9 horses with recent S. equi infections, 17 horses without known exposure to S. equi, but without a history of respiratory disease in the preceding 4 months, and 2 horses with clinical purpura hemorrhagica. Serum IgA titers to culture supernatant protein antigen were highest in recently infected horses (P less than 0.001). Serial determinations of antibody titers in the horses with purpura showed that IgG antibodies to both S. equi M-like protein and culture supernatant protein antigens were undetectable initially, but later rose coincidental with clinical recovery from the disease. Possible mechanisms for these findings are discussed. PMID- 1748980 TI - Interleukins: biological properties and therapeutic potential. AB - Interleukins are biologically active glycoproteins derived primarily from activated lymphocytes and macrophages. Tremendous insight into the biochemical and biological properties of interleukins has been gained with advances in recombinant DNA technology, protein purification, and cell-culture techniques. The biological properties of interleukins include induction of T-lymphocyte activation and proliferation, augmentation of neutrophil, macrophage, and T lymphocyte cytotoxicity, and promotion of B lymphocyte and multilineage bone marrow stem-cell precursor growth and differentiation. Interleukins may play a role in the pathogenesis of several important diseases. Interleukin therapy is likely to play an important role in the treatment of cancer, infectious diseases, and immunodeficiency syndromes. PMID- 1748982 TI - Comparison of latex agglutination, indirect hemagglutination, and ELISA techniques for the detection of Toxoplasma gondii-specific antibodies in the serum of cats. AB - The primary purpose of this study was to determine whether commercially available latex agglutination and indirect hemagglutination kits for the detection of Toxoplasma gondii-specific antibodies were capable of detecting T. gondii specific immunoglobulin M (IgM) in the serum of cats. Serum samples from 35 cats containing either T. gondii-specific IgM, T. gondii-specific immunoglobulin G (IgG), or both were collected. Each serum sample was assayed using a latex agglutination kit, an indirect hemagglutination kit, an enzyme-linked immunosorbent assay (ELISA) for the detection of T. gondii-specific IgG, and an ELISA for the detection of T. gondii-specific IgM. When serum samples containing only T. gondii-specific IgM as determined by ELISA were assayed, the latex agglutination kit and the indirect hemagglutination kit detected antibodies in 33.3% and 13.3%, respectively. When T. gondii-specific IgG was present in a serum sample, the results from the latex agglutination kit, the indirect hemagglutination kit, and the IgG-ELISA were similar; however, there was a wide variation in titer magnitude results between the three assays. It was concluded that the latex agglutination kit and the indirect hemagglutination kit did not adequately detect T. gondii-specific IgM in feline serum. PMID- 1748981 TI - A comparison of simultaneously collected arterial, mixed venous, jugular venous and cephalic venous blood samples in the assessment of blood-gas and acid-base status in the dog. AB - Blood samples were collected simultaneously from the pulmonary artery, jugular vein, cephalic vein, and carotid artery in awake dogs. Blood-gas and acid-base values were measured from these blood samples in normal dogs and in dogs after production of metabolic acidosis and metabolic alkalosis. The values obtained from each of the venous sites were compared with those obtained from arterial blood to determine if venous blood from various sites accurately reflected acid base balance and could therefore be used in the clinical patient. The results of this study demonstrated significant differences between the blood from various venous sites and the arterial site for PCO2 and pH in all acid-base states. Significant differences for standard bicarbonate (SHCO3) were found only when jugular and cephalic venous blood were compared with arterial blood in dogs with a metabolic acidosis. No significant differences were found for BE when blood from the venous sites was compared with arterial blood. The values for pH, HCO3, TCO2, BE, and SHCO3 measured on blood collected at the various venous sites were found to correlate well with those obtained from arterial blood, with a correlation coefficient of 0.99 for HCO3, TCO2, BE, and SHCO3. These correlation coefficients, together with similar values in BE at all collection sites, indicate that, in the dog with normal circulatory status, blood from any venous site will accurately reflect the acid-base status of the patient. PMID- 1748983 TI - Treatment of acute digoxin toxicosis with digoxin immune fab (Ovine). PMID- 1748984 TI - The process of becoming Board certified. PMID- 1748985 TI - Congenital hypothyroid dwarfism in a family of giant schnauzers. PMID- 1748986 TI - Interactions between viral coat protein and a specific binding region on turnip crinkle virus RNA. AB - The turnip crinkle virus coat protein binding sites in the ribonucleoprotein complex resulting from virion dissociation have been identified previously. In this study, RNA binding characteristics of viral coat protein to a region encompassing the protected RNA fragments Fa, Ff, and Fc (Fafc) have been investigated further using an RNA transcript (the Fafc fragment). These experiments have shown that coat protein requires no additional viral RNA elements to bind to this region. Such binding was shown to be specific for turnip crinkle virus coat protein using an ultra-violet light cross-linking assay. Gel mobility shift analyses demonstrated that the protein-RNA interactions produced two complexes: a homogeneous small ribonucleoprotein complex, and larger complexes which failed to migrate into gels. High salt and limiting protein concentrations favored the formation of the small ribonucleoprotein complex, whereas low salt and excess protein concentrations favored the larger complexes. RNA competition experiments demonstrated that small ribonucleoprotein complex formation coincided with specific RNA binding of the coat protein to the Fafc fragment. In addition, the coat protein possessed a poly(U)-binding site(s), which enabled it to interact with single-stranded RNA in a sequence non-specific manner to form large complexes. The results suggest that the coat protein contains both specific and non-specific RNA binding activities located at physically distinct sites. These results are consistent with the proposed assembly model for turnip crinkle virus. PMID- 1748987 TI - Crystallization and preliminary data for the ferric form of Lucina pectinata hemoglobin I. AB - Cytoplasmic monomeric hemoglobin I from the bacteria-harboring gill of the bivalve mollusc Lucina pectinata has been crystallized in a form suitable for atomic resolution X-ray structural investigations. The crystals have been grown at pH 4.8, in 0.05 M-acetate buffer, using 2.6 M-ammonium sulfate as precipitating agent. The crystals belong to the monoclinic space group P2(1), with unit cell constants a = 50.0 A, b = 38.6 A, c = 42.1 A, beta = 107.1 degrees, and contain one molecule (14,000 Mr) in the asymmetric unit. By means of single crystal microspectrophotometry it has been shown that the crystals contain the ferric form of L. pectinata "sulfide reactive" hemoglobin I. On the other hand, by careful control of the buffering medium composition, it has been possible to obtain stable crystals of the deoxy, oxy and sulfide forms of the protein. PMID- 1748988 TI - Purification, crystallization and preliminary X-ray diffraction studies of the PvuII endonuclease. AB - The PvuII endonuclease (PvuIIR) is a restriction enzyme from a type II restriction-modification system of Proteus vulgaris coded on plasmid pPvu1. The protein recognizes the DNA sequence 5' CAG'CTG 3' and shows no sequence homology to other restriction enzymes. This makes PvuIIR an interesting subject for structural determination. A purification procedure was developed that yields milligram quantities of the PvuIIR from plasmids expressed in the Escherichia coli strain HB101. The protein was crystallized using ammonium sulphate as precipitant. The crystals are orthorhombic, space group P2(1)2(1)2 with cell dimensions: a = 84.2 A, b = 106.2 A, c = 46.9 A. The asymmetric unit contains one PvuIIR dimer. Diffraction extends to 2.3 A, so the crystals may permit structural determination at atomic resolution. PMID- 1748989 TI - Scanning transmission electron microscopic mass determination of in vitro self assembled smooth muscle myosin filaments. AB - We have measured the mass per unit length of in vitro self-assembled smooth muscle myosin filaments, using scanning transmission electron microscope darkfield images of freeze-dried samples. The measured values were integral multiples, usually 1, 2, 3 or 4, of 75 kDa per nm. The data corroborate an earlier proposal, that these filaments are built from monolayer sheets of molecules, each sheet having two antiparallel myosin molecules per 14.3 nm of its length. PMID- 1748990 TI - Crystallization and preliminary X-ray diffraction studies of the spinach chloroplast thioredoxin f. AB - Thioredoxins are low-molecular-mass proteins that function as hydrogen carriers in DNA synthesis and in the transformation of sulfur metabolites. They also act as regulatory proteins in the light-dependent enzyme activation during photosynthesis. F-type thioredoxin from spinach chloroplasts, a monomeric protein of 113 amino acid residues, has been found to specifically activate fructose-1,6 bisphosphatase and other key enzymes of CO2 assimilation. It has been crystallized in the monoclinic system, space group P2(1) with a = 30.6 A, b = 63.1 A, c = 31.6 A and beta = 110.7 degrees. The crystals are suitable for X-ray diffraction studies. PMID- 1748991 TI - Crystallization of a complex of hemoglobin components II and III of the symbiont harboring clam Lucina pectinata. AB - Diffraction data to 3.1 A resolution were collected on crystals of a complex of components II and III of the cytoplasmic hemoglobin of the symbiont-harboring clam Lucina pectinata. The crystal system is tetragonal, a = 76.3 A, c = 153.1 A and the space group is P42212. The asymmetric unit probably contains a dimer of the tetrameric complex. PMID- 1748992 TI - Control regions of an archaeal gene. A TATA box and an initiator element promote cell-free transcription of the tRNA(Val) gene of Methanococcus vannielii. AB - To identify the DNA sequences required for initiation of transcription in archaea, the 5'-flanking region of the tRNA(Val) gene of Methanococcus vannielii was modified by deletions, restructuring and site-directed mutagenesis, and the tRNA encoding sequence was replaced by a fortuitous Escherichia coli sequence. The effects of these mutations on promoter function were tested in an homologous cell-free transcription system. The DNA region from position -35 to +9 relative to the transcription start site was sufficient for maximal initiation of cell free transcription. Removal of the DNA region between -35 and -30 reduced initiation by a factor of 2. Deletions extending to position -24 almost completely abolished specific transcription. Analysis of 16 site-specific mutations in the region from -33 to +2 provided evidence that a conserved A + T rich sequence (TATA box), centered at -25, is essential for initiation of transcription. Single point mutations in six positions of the TATA box reduced initiation of transcription from 0.2 to 0.01 of wild-type levels. A second conserved motif at the transcription start site (consensus ATGC) could be replaced by some sequences containing a pyrimidine-purine dinucleotide but appeared necessary for a maximal rate of gene transcription. Mutations altering the spacing between the two conserved elements demonstrated that initiation occurs at a strictly defined distance of 22 to 27 base-pairs downstream from the TATA box. Our results support the conclusion that the TATA box is the major DNA region mediating promoter recognition, influencing the efficiency of transcription and specifying the site of transcription initiation. This Methanococcus promoter element closely resembles in structure and function the TATA box of promoters of eukaryotic protein-encoding genes transcribed by RNA polymerase II. PMID- 1748993 TI - Detailed physical map and set of overlapping clones covering the genome of the archaebacterium Haloferax volcanii DS2. AB - An integrated approach of "bottom up" and "top down" mapping has produced a minimal set of overlapping cosmid clones covering 96% of the 4140 kilobase-pairs (kbp) Haloferax volcanii DS2 genome and a completely closed physical map. This genome is partitioned into five replicons: a 2920 kbp chromosome and four plasmids, of 690 kbp (pHV4), 442 kbp (pHV3), 86 kbp(pHV1) and 6.4 kbp (pHV2). A restriction map for six infrequently-cutting restriction enzymes was constructed, representing a total of 903 sites in the cloned DNA. We have placed the two ribosomal RNA operons, the genes for 7 S RNA and for RNaseP RNA and 22 protein coding genes on the map. Restriction site frequencies show significant variation in different portions of the genome. The regions of high site density correspond to halobacterial satellite or FII DNA which includes two small regions of the chromosome, the plasmids pHV1 and pHV2, and half of pHV4, but not pHV3. PMID- 1748994 TI - By-passing immunization. Human antibodies from V-gene libraries displayed on phage. AB - We have mimicked features of immune selection to make human antibodies in bacteria. Diverse libraries of immunoglobulin heavy (VH) and light (V kappa and V lambda) chain variable (V) genes were prepared from peripheral blood lymphocytes (PBLs) of unimmunized donors by polymerase chain reaction (PCR) amplification. Genes encoding single chain Fv fragments were made by randomly combining heavy and light chain V-genes using PCR, and the combinatorial library (greater than 10(7) members) cloned for display on the surface of a phage. Rare phage with "antigen-binding" activities were selected by four rounds of growth and panning with "antigen" (turkey egg-white lysozyme (TEL) or bovine serum albumin) or "hapten" (2-phenyloxazol-5-one (phOx], and the encoding heavy and light chain genes were sequenced. The V-genes were human with some nearly identical to known germ-line V-genes, while others were more heavily mutated. Soluble antibody fragments were prepared and shown to bind specifically to antigen or hapten and with good affinities, Ka (TEL) = 10(7) M-1; Ka (phOx) = 2 x 10(6) M-1. Isolation of higher-affinity fragments may require the use of larger primary libraries or the construction of secondary libraries from the binders. Nevertheless, our results suggest that a single large phage display library can be used to isolate human antibodies against any antigen, by-passing both hybridoma technology and immunization. PMID- 1748995 TI - Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. AB - The very high concentration of macromolecules within cells can potentially have an overwhelming effect on the thermodynamic activity of cellular components because of excluded volume effects. To estimate the magnitudes of such effects, we have made an experimental study of the cytoplasm of Escherichia coli. Parameters from cells and cell extracts are used to calculate approximate activity coefficients for cytoplasmic conditions. These calculations require a representation of the sizes, concentrations and effective specific volumes of the macromolecules in the extracts. Macromolecule size representations are obtained either by applying a two-phase distribution assay to define a related homogeneous solution or by using the molecular mass distribution of macromolecules from gel filtration. Macromolecule concentrations in cytoplasm are obtained from analyses of extracts by applying a correction for the dilution that occurs during extraction. That factor is determined from experiments based upon the known impermeability of the cytoplasmic volume to sucrose in intact E. coli. Macromolecule concentrations in the cytoplasm of E. coli in either exponential or stationary growth phase are estimated to be approximately 0.3 to 0.4 g/ml. Macromolecule specific volumes are inferred from the composition of close-packed precipitates induced by polyethylene glycol. Several well-characterized proteins which bind to DNA (lac repressor, RNA polymerase) are extremely sensitive to changes in salt concentration in studies in vitro, but are insensitive in studies in vivo. Application of the activity coefficients from the present work indicates that at least part of this discrepancy arises from the difference in excluded volumes in these studies. Applications of the activity coefficients to solubility or to association reactions are also discussed, as are changes associated with cell growth phase and osmotic or other effects. The use of solutions of purified macromolecules that emulate the crowding conditions inferred for cytoplasm is discussed. PMID- 1748996 TI - Refinement of the three-dimensional solution structure of barley serine proteinase inhibitor 2 and comparison with the structures in crystals. AB - The three-dimensional structure of barley serine proteinase inhibitor, CI-2, has been determined using nuclear magnetic resonance spectroscopy. The present structure determination is a refinement of the structure previously determined by us, using in the present case stereo-specific assignments, and a virtually complete set of assignments of the two-dimensional nuclear Overhauser spectrum. The structure determination is based on the identification of more than 1300 nuclear Overhauser effects, of which 961 were used in the structure calculation as distance restraints, and on 94 dihedral angle restraints, of which 31 are for chi 1 angles in defined chiral centers. These have been used to calculate a series of 20 three-dimensional structures using a combination of distance geometry, simulated annealing and restrained molecular dynamics. Each of the 20 structures was in agreement within less than 0.5 A of each of the distance restraints and with all dihedral angle restraints. When compared to the geometric average structure of the 20 refined structures the root-mean-square differences for the backbone atoms were 0.8 (+/- 0.2) A and for all atoms were 1.6 (+/- 0.2) A. By comparison, the values obtained for the structures determined previously were 1.4 (+/- 0.2) A and 2.1 (+/- 0.1) A, respectively. The structures were also compared to the structure determined in the crystalline state by X-ray diffraction showing root-mean-square differences of 1.6 (+/- 0.2) A and 2.8 (+/- 0.2) A for the backbone and all atoms, respectively. Common features of the solution structure and the two crystal structures are the four-stranded beta structure, composed of a pair of parallel strands, and three pairs of antiparallel beta-strands flanked on one side by a 12-residue alpha-helix and on the other side by a loop containing the serine proteinase binding site. The new analysis of the structure has revealed an additional pair of antiparallel beta strands, consisting of residues 65 to 67 and 81 to 83, that was not seen in either of the crystal structures or the previous solution structure. Identification of this was based on nuclear magnetic resonance evidence for the hydrogen bond (67HN to 81CO) not reported previously. Also the presence of a bifurcated hydrogen bond involving Phe69 CO and HN atoms of Ala77 and Gln78 was observed in solution but not in crystals. Minor differences between the two structures were observed in the phi-angles of residues Met59 and Glu60 in the inhibitory site. PMID- 1748997 TI - DNase I-induced DNA conformation. 2 A structure of a DNase I-octamer complex. AB - The structure of a complex between DNase I and d(GCGATCGC)2 has been solved by molecular replacement and refined to an R-factor of 0.174 for all data between 6 and 2 A resolution. The nicked octamer duplexes have lost a dinucleotide from the 3' ends of one strand and are hydrogen-bonded across a 2-fold axis to form a quasi-continuous double helix of 14 base-pairs. DNase I is bound in the minor groove of the B-type DNA duplex forming contacts in and along both sides of the minor groove extending over a total of six base-pairs. As a consequence of binding of DNase I to the DNA-substrate the minor groove opens by about 3 A and the duplex bends towards the major groove by about 20 degrees. Apart from these more global distortions the bound duplex also shows significant deviations in local geometry. A major cause for the observed perturbations in the DNA conformation seems to be the stacking type interaction of a tyrosine ring (Y76) with a deoxyribose. In contrast, the enzyme structure is nearly unchanged compared to free DNase I (0.49 A root-mean-square deviations for main-chain atoms) thus providing a rigid framework to which the DNA substrate has to adapt on binding. These results confirm the hypothesis that groove width and stiffness are major factors determining the global sequence dependence of the enzyme's cutting rates. The nicked octamer present in the crystals did not allow us to draw detailed conclusions about the catalytic mechanism but confirmed the location of the active site near H134 on top of the central beta-sheets. A second cut of the DNA induced by diffusion of Mn2+ into the crystals may suggest the presence of a secondary active site in DNase I. PMID- 1748998 TI - Molecular basis of co-operativity in protein folding. AB - The folding/unfolding transition of proteins is a highly co-operative process characterized by the presence of very few or no thermodynamically stable partially folded intermediate states. The purpose of this paper is to present a thermodynamic formalism aimed at describing quantitatively the co-operative folding behavior of proteins. In order to account for this behavior, a hierarchical algorithm aimed at evaluating the folding/unfolding partition function has been developed. This formalism defines the partition function in terms of multiple levels of interacting co-operative folding units. A co operative folding unit is defined as a protein structural element that exhibits two-state folding/unfolding behavior. At the most fundamental level are those structural elements that behave co-operatively as a result of purely local interactions. Higher-order co-operative folding units are formed through interactions between different structural elements. The hierarchical formalism utilizes the crystallographic structure of the protein as a template to generate partially folded conformations defined in terms of co-operative folding units. The Gibbs free energy of those states and their corresponding statistical weights are then computed using experimental energetic parameters determined calorimetrically. This formalism has been applied to the case of myoglobin. It is shown that the hierarchical partition function correctly predicts the presence, energetics and co-operativity of the heat and cold denaturation transitions. The major contribution to the co-operative folding behavior arises from the solvent exposure of non-polar residues located in regions complementary to those that have undergone unfolding. This entropically uncompensated and energetically unfavorable solvent exposure characterizes all partially folded states but not the unfolded state, thus minimizing the population of partially folded intermediates throughout the folding/unfolding transition. PMID- 1748999 TI - Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution. AB - The three-dimensional structure of the highly thermostable 3-isopropylmalate dehydrogenase (IPMDH) from Thermus thermophilus has been determined by the multiple isomorphous replacement method and refined to 2.2 A resolution. The final R-factor is 0.185 for 20,307 reflections. The crystal asymmetric unit has one subunit consisting of 345 amino acid residues. The polypeptide chain of this subunit is folded into two domains (first and second domains) with parallel alpha/beta motifs. The domains are similar in their conformations and folding topologies, but differ from those of the NAD-binding domains of such well-known enzymes as the alcohol and lactate dehydrogenases. A beta-strand that is a part of the long arm-like polypeptide protruding from the second domain comes into contact with another subunit and contributes to the formation of an isologous dimer with a crystallographic 2-fold symmetry. Close subunit contacts are also present at two alpha-helices in the second domain. These helices strongly interact hydrophobically with the corresponding helices of the other subunit to form a hydrophobic core at the center of the dimer. Two large pockets that exist between the first domain of one subunit and the second domain of the other include the amino acid residues responsible for substrate binding. These results indicate that the dimeric form is essential for the IPMDH to express enzymatic activity and that the close subunit contact at the hydrophobic core is important for the thermal stability of the enzyme. PMID- 1749000 TI - Construction of new ligand binding sites in proteins of known structure. I. Computer-aided modeling of sites with pre-defined geometry. AB - We have devised a molecular model building computer program (DEZYMER) which builds new ligand binding sites into a protein of known three-dimensional structure. It alters only the sequence and the side-chain structure of the protein, leaving the protein backbone fold intact by definition. The program searches for a constellation of backbone positions arranged such that if appropriate side-chains were placed there, they would bind the ligand according to a pre-defined geometry of interaction specified by the experimentalist. These binding sites are introduced by the program by taking into account simple rules such as steric hindrance, atomic close-packing and hydrogen bond patterns, which are known to maintain the integrity of a protein structure to a first approximation. A test case is presented in this paper where the copper binding site found in blue-copper proteins such as plastocyanin, azurin and cupredoxin is introduced into Escherichia coli thioredoxin. The model building of one of the solutions found by the program is presented in some detail. The experimental construction and properties of this new protein are described in an accompanying paper. It is hoped that this program provides a general method for the design of ligand binding sites and enzyme active sites, which can then be tested experimentally. PMID- 1749001 TI - A simplified mechanical model of proteins tested on the globin fold. AB - It has been shown that the distribution of presently known protein loop lengths is consistent with even the simplest available theory of rubber-like elasticity, and with the idea that such loops generate an entropically derived end-to-end tension. It has also been asserted that the molten globule phase, just like the native form, must be mechanically stable, and that a simple demonstration of the potential for mechanical stability would be a powerful test in predictions of new protein folds. This paper amplifies this suggestion by explicit calculation of a familiar but non-trivial test case: sperm-whale myoglobin. The method used is to describe the protein molecule in terms of a highly simplified mechanical model bearing some resemblance to a pre-stressed mechanism. The alpha-helices are treated as rigid rods and the loops are treated as elastic strings. The entropic tensions exerted by the loops are imposed on the mechanism using an approximation proposed earlier. The helices are then held to generate frictionless reaction forces at their mutual points of contact. These contact forces are calculated to null out maximally the effects of the loop tensions, and hence stabilize the molecule. It is shown that the crystallographically determined structure of myoglobin has a significantly higher mechanical stability on this model than does any of a previously published set of combinatorially generated predictions. Amongst the predictions alone, the best is also the one with the highest stability. It is anticipated that this result could be of general importance in sorting or filtering out bad predictions. A further exciting feature of the model is that it offers a natural explanation for the strong conservation of the C2 proline and the invariably long unconserved sequence from the end of the C helix to the start of the E helix in the globins and phycocyanins. PMID- 1749002 TI - Insulin increases the rate of degradation of 2-deoxy-glucose-6-phosphate in the perfused rat heart: a 31P NMR study. AB - The effect of insulin on the production and degradation of 2-deoxyglucose-6 phosphate (2DG6P) from 2-deoxyglucose (2DG) in the Langendorff-perfused rat heart was studied by 31P NMR. The 2DG concentrations ranged from 0.25 to 20 mM in the 5 mM acetate perfusion medium, and from 2 to 4 mM in the 12 mM glucose medium. With acetate as the carbon source, the apparent Km for the production of 2DG6P was 7 mM and Vmax was 1.8 mumols/min/mg prot. Insulin enhanced Vmax 7-fold without change in Km of the transporter. With glucose perfusion, insulin had no effect on the initial rate of production of 2DG6P. The interpretation is that glucose phosphorylation is regulated by work when glucose is the energy substrate. In acetate-perfused hearts, in the conditions where the 2DG6P content reached a plateau, the rate of production of 2DG6P (equal to the measured degradation rate, see below) was eight times smaller than the initial rate, both with and without insulin. In glucose-perfused hearts, it was the same as the initial rate. The degradation of 2DG6P upon interruption of 2DG perfusion was exponential. The time constant was the same in acetate or glucose. It was strongly affected by insulin, being 225 +/- 60 min without, and 92 +/- 13 min with insulin. The observation that 2DG6P degradation is sensitive to insulin in the heart shows that its rate may vary. This possibility should be kept in mind in the analysis of PET studies of glucose metabolism. PMID- 1749003 TI - Evaluation of mRNA levels by the polymerase chain reaction in small cardiac tissue samples. AB - Doxurubicin is an effective and widely used chemotherapeutic agent. However, use of this drug is often limited by its cardiotoxic side effects. We have observed that an early event accompanying doxorubicin cardiomyopathy is a selective decrease in levels of muscle gene transcripts in cardiac tissue (Ito et al., Proc. Natl. Acad. Sci. USA 87: 4275-4279). Since this decrease precedes ultrastructural evidence of cardiac damage, measurements of muscle transcripts might assist in the clinical evaluation of doxorubicin cardiotoxicity. We have therefore assessed the utility of the polymerase chain reaction in the measurement of mRNA in control and doxorubicin-treated animals. These measurements were performed on small tissue samples that simulate endomyocardial biopsies. We measured cardiac alpha-actin transcripts as a fraction of ferritin heavy chain transcripts using the method described by Chelly et al. (Nature 333: 858-860, 1988). 0.5 micrograms of total RNA, an amount equivalent to that obtainable from a typical endomyocardial biopsy, was efficiently co-amplified with cardiac alpha-actin and ferritin heavy chain specific primers. The cardiac alpha-actin/ferritin heavy chain ratio calculated from the PCR results correlated well (R = 0.981) with results obtained using Northern blot analysis of 10 micrograms RNA. The correlation was maintained over a wide range of cardiac alpha actin transcript abundance. These results show that mRNA from cardiac tissue can be estimated by the polymerase chain reaction, even from a small, endomyocardial biopsy-sized sample. PMID- 1749004 TI - Effects of acidosis and ATP depletion on cardiac muscle electron transfer complex I. AB - The loss of NADH-ubiquinone oxidoreductase activity, the activity of mitochondrial electron transfer complex I, underlies the loss of mitochondrial phosphorylating respiration with NAD-linked substrates observed during myocardial ischemia. In the present study the loss of complex I activity was found to be considerably more rapid during zero-flow ischemia in rat heart, a fast heart-rate heart, than in dog heart, a slow heart-rate heart. Moreover, the greater rapidity of the loss of complex I activity in the ischemic rat heart appeared to reflect the more rapid and more severe decreases in tissue pH and in tissue ATP characteristic of the zero-flow ischemic rat heart compared to zero-flow ischemic dog heart. In vitro enzyme inactivation studies on dog heart electron transfer complex I showed that the enzyme was approximately 40% inactivated after 1 minute by incubation at pH 6.0 in the absence of added ATP. The effect of low pH upon enzyme activity was mitigated considerably by the presence of one to two mM MgATP in the incubation mixtures. Moreover, a portion of the activity-sparing effect of MgATP was still observed in the presence of the uncoupler, FCCP. This latter observation suggests that part of the function-stabilizing effect of ATP was attributable to inner membrane energization and part appeared to have been due to a direct protective effect of ATP upon the complex. PMID- 1749005 TI - Cellular source and role of adenosine in isoproterenol-induced coronary vasodilatation. AB - The role of adenosine and its cellular source in isoproterenol-induced coronary vasodilatation was investigated in isolated perfused rat hearts prelabelled with [3H]adenosine. Time courses (times for half-maximal increase) were measured for changes in oxygen consumption (2.23 +/- 0.22 min), coronary flow (3.30 +/- 0.33 min), concentrations of effluent radioactivity (3.92 +/- 0.30 min) and adenosine and its metabolites (inosine, hypoxanthine and xanthine) (2.00 +/- 0.23 min). Isoproterenol stimulation decreased the cellular energy state and increased the concentration of tissue adenosine and its metabolites. Coronary flow was linearly correlated with tissue adenosine (r = 0.85) and phosphorylation potential (r = 0.82) and tissue adenosine also showed a linear correlation with phosphorylation potential (r = -0.84) and tissue free [AMP] (r = 0.79). The specific radioactivities of tissue nucleotides remained constant, but those of adenosine, inosine and hypoxanthine + xanthine were decreased by 42%, 26% and 46%, respectively. Purine compound concentrations increased during isoproterenol stimulation from basal values of 56 +/- 23, 98 +/- 33 and 44 +/- 19 nM to 388 +/- 173, 583 +/- 156 and 178 +/- 27 nM, respectively. The basal specific radioactivity ratio of adenosine:inosine:(hypoxanthine + xanthine) in the effluent perfusate was 1:0.5:7, but the specific radioactivities decreased rapidly upon isoproterenol stimulation, and at 3 min the ratio had changed to 1:2.5:16.5. The time courses of release and the changes in the specific radioactivities of the nucleosides indicate that adenosine release occurred mainly from cardiomyocytes, and that the release of adenosine and its metabolites from the cardiomyocytes preceded that from the endothelium. It is also shown that adenosine release during catecholamine stimulation occurs concomitantly with a decrease in the cellular energy state and AMP accumulation. This is in accord with the adenosine hypothesis of coronary vasoregulation. PMID- 1749006 TI - The protective role of glucose on ischemic-reperfused hearts: effect of dietary fats. AB - The dietary polyunsaturated fatty acids are well known to promote the cardiac output and to protect the myocardium against arrhythmias. The exogenous glucose is generally considered as a protective agent against arrhythmias resulting from ischemia and reperfusion. But the effects of dietary fats, which also influence arrhythmias, on this beneficial effect of glucose has not been yet considered. We have studied the effects of a 7 days diet with or without polyunsaturated fatty acids on the cardiac performance and arrhythmias of isolated rat hearts, perfused with saline containing either glucose 5.5 mM or 11 mM. Acute regional ischemia was produced by ligature of the left main coronary artery with subsequent release to achieve reperfusion for some hearts. Previously, our results showed that the dietary polyunsaturated fatty acids led to an enhancement of the cardiac performance and to a decreased susceptibility to arrhythmias. The present data showed that the protective action of the exogenous glucose appeared to be dependent of the dietary lipid profile. Dietary polyunsaturated fatty acids increase cardiac performance under ischemia and decrease ventricular arrhythmias' occurrence under ischemia and on reperfusion. It might be related to endogenous substrate utilization and exogenous glucose availability which was influenced by the coronary flow. PMID- 1749007 TI - The isoproterenol-induced chloride current and cardiac resting potential. AB - Isoproterenol can induce potentially arrhymthogenic depolarizations of the resting membrane of single guinea-pig ventricular myocytes. This effect on resting potential of single guinea-pig ventricular myocytes differs qualitatively from results obtained by others from intact cardiac muscle preparations and also differs from our experience with single dog ventricular myocytes. We performed experiments on dog and guinea-pig ventricular myocytes in an attempt to clarify the effects of isoproterenol on the resting potential of mammalian ventricular myocytes. Voltage recordings with 40-60 M omega 3 M potassium chloride filled microelectrodes revealed an isoproterenol-induced depolarization of 4.3 +/- 1.0 mV in guinea-pig but no depolarization in dog myocytes. Activation of an outwardly rectifying chloride current is responsible for the isoproterenol induced depolarization of guinea-pig ventricular myocytes. Our whole cell patch clamp recordings consistently revealed such a current in guinea-pig cells but always failed to demonstrate an isoproterenol-induced chloride current in dog myocytes under identical conditions. In contrast to single cells, isoproterenol did not depolarize intact guinea-pig papillary muscle when potential was recorded with 40-60 M omega 3 M KCl filled electrodes. Furthermore, we saw no depolarization in single guinea-pig myocytes when recording electrodes did not contain chloride. We conclude that: (1) despite activation of a chloride current, isoproterenol does not significantly depolarize guinea-pig ventricular muscle unless the driving force for the current at the resting potential is increased by elevating [Cl]i above physiological levels, and (2) an isoproterenol-induced chloride current, although demonstrable in guinea-pig ventricular cells, is not present in healthy dog ventricular cells. PMID- 1749009 TI - Reimbursement influences choice of cancer therapy. PMID- 1749008 TI - Choosing the right radionuclide and antibody for intraperitoneal radioimmunotherapy. PMID- 1749010 TI - Biotech industry flourishes with cancer research advances. PMID- 1749012 TI - NIH formulates a strategic plan. PMID- 1749013 TI - Twenty-one states operate cancer pain initiatives. PMID- 1749011 TI - Father's lifestyle can have fetal consequences. PMID- 1749014 TI - Heavy tobacco use in high schools needs to be addressed. PMID- 1749015 TI - Community Intervention Trial for Smoking Cessation (COMMIT): summary of design and intervention. COMMIT Research Group. AB - The Community Intervention Trial for Smoking Cessation (COMMIT) is a multicenter project created to test a comprehensive smoking control intervention. COMMIT was designed to effectively reach cigarette smokers, especially heavy smokers, and to aid them in achieving and maintaining long-term cessation of cigarette smoking. COMMIT was also designed to work through communities, using existing media channels, major organizations, and social institutions capable of influencing smoking behavior in large groups of people. This ongoing trial was begun in 1989 in 11 matched pairs of communities. Each pair consists of one community randomized to intervention conditions and one community randomized to comparison conditions. A comprehensive set of mandated activities is organized around four task forces encompassing health care providers, work sites and organizations, cessation resources and services, and public education. Intervention activities are adapted and implemented in each community through a local community board that provides oversight and management of COMMIT activities. Cessation rates will be assessed in randomly selected cohorts of heavy cigarette smokers, identified at the baseline survey and tracked for 5 years, as estimators of the overall quit rates in both intervention and comparison communities. Various data collection methods will be used to provide intermediate outcome measurement and to evaluate implementation. These methods include cross-sectional community surveys and surveys of health providers, work sites, religious organizations, cessation resource providers, and other systems used to track smoking control activities. The trial will have an impact on more than 200 000 adult smokers. PMID- 1749016 TI - Analysis of the role of cancer prevention and control measures in reducing cancer mortality. AB - One goal of the war against cancer is to create declines in cancer mortality rates. A decrease in these rates can only occur in two ways: 1) a decrease in incidence rates and 2) a real increase in overall survival rates. Reductions in incidence rates can be envisioned to occur through three mechanisms (in order of the time course of cancer): 1) reduction or amelioration of environmental or lifestyle risk factors, 2) use of agents that prevent the occurrence of cancer by blocking the progression to cancer, and 3) early detection at a preneoplastic state combined with treatment that prevents or delays progression to invasive cancer. "True" increases in overall survival can occur by two mechanisms (in order of the time course of cancer): 1) early detection of cancer by screening tests and subsequent effective treatment and 2) advancements in treatment. Unique patterns or "fingerprints" of stage-specific incidence and overall incidence and of survival rates characterize the various cancer prevention and control mechanisms that can decrease mortality rates. The rates are presented for five organ sites that have shown reduced cancer mortality. The patterns of rates for breast cancer for women under the age of 65 years were most consistent with early detection. The testicular cancer fingerprints were most consistent with advances in treatment, whereas cervical cancer rates were most consistent with the detection of preneoplastic lesions. The stomach cancer fingerprints were indicative of reductions in lifestyle or environmental risks, and colorectal cancer rates were indicative of a combination of treatment advances and early detection. These fingerprint patterns can be extended to other situations in which mortality trends are changing in order to suggest possible causes of observed changes. Limitations of this model are also discussed. PMID- 1749017 TI - Is there evidence of a therapy-related increase in germ cell mutation among childhood cancer survivors? AB - Few studies have examined human population data for evidence of an association between environmental mutagens and genetic disease. Our objective was to determine whether study of pregnancies and offspring of childhood cancer survivors would show evidence that therapy potentially mutagenic to germ cells is associated with increased risk of miscarriage, serious congenital abnormalities, or altered sex ratio. We analyzed information from patients' general practitioners for 2286 survivors of childhood cancer (1049 females and 1237 males) who were exposed or not exposed to direct irradiation of the abdomen or gonads or treatment with an alkylating agent. In addition, external control data based on the general population were used for some of the comparisons relating to congenital abnormalities and sex ratio. Data on reproductive history were complete for 1037 female survivors, who had 944 completed pregnancies, and 1078 male survivors, who produced 537 offspring. For the female survivors given abdominal or gonadal irradiation, there was an excess of miscarriages for the total number of pregnancies (17%) and for first pregnancies (19%), compared with the proportion for the total number of pregnancies in the females with similar neoplasms who were not exposed to such therapy (9%) and for first pregnancies in these females (8%). These results show re-emergence of an association suggested in our previous report of an increased risk of miscarriage as well as low birth weight among off-spring of female survivors of childhood cancer who received abdominal irradiation. In that study, it was considered unlikely that the association was due to germ cell mutation. Data in the present study do not show an association of exposure to therapy potentially mutagenic to germ cells with sex ratio, or with occurrence of serious congenital abnormalities in the offspring of male or female survivors of such therapy. However, the question of a possible germ cell mutagenic effect of therapy will be adequately addressed only through an international collaborative effort. PMID- 1749018 TI - Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors. AB - Dunning R3327-AT prostate carcinomas growing in Fischer X Copenhagen rats were treated with interstitial photodynamic therapy (PDT--15 mg/kg Photofrin II 4 hours before illumination with 630-nm light via four parallelly implanted optical fibers) at different light intensities. Forty to 60 minutes after treatment, 31P nuclear magnetic resonance spectra of tumors in anesthetized animals were obtained at 2.35 Tesla using surface coil localization. Areas under resonance peaks were normalized to the area under the peak of a phosphorus standard positioned at a fixed distance on the opposite side of the surface coil. Tumor concentrations of phosphomonoesters and phosphodiesters showed no change after tumor light doses up to 3000 J. Phosphocreatine, alpha-adenosine triphosphate (ATP), beta-ATP, and gamma-ATP signals decreased and inorganic phosphate signals increased with increasing light doses. The intratumor pH did not change significantly at these short times after PDT. In other R3327-AT and R3327-H tumor bearing animals, [3H]misonidazole was administered 30 minutes prior to PDT treatments of both tumors. Twenty-four hours later, the tumors were resected in toto, and levels of retained [3H]misonidazole were determined in lased tumor specimens by liquid scintillation procedures. The amount of [3H]misonidazole activity in tumor tissue (covalently bound after hypoxic reduction) increased with light doses up to 3000 J. Sensitizer-adduct formation was found to correlate with the ratio of the concentration of inorganic phosphate to that of beta-ATP, both of which are presumed measures of tumor oxygenation status. These measurements have high-lighted the heterogenous nature of the oxygenation status of these experimental tumors. The precision of each assay for estimating tumor oxygenation is discussed. PMID- 1749019 TI - Enhanced expression of interleukin-6 in primary human renal cell carcinomas. AB - We have demonstrated interleukin-6 (IL-6) production by human renal carcinoma cells. The IL-6 gene expression was detected by Northern blot analysis in 22 of 43 primary renal cell carcinoma tissues and in five of seven renal cell carcinoma cell lines. Immunohistochemical analysis confirmed the expression of IL-6 by the tumor cells. Patients with a high-level expression of IL-6 had significantly greater incidences of lymph node metastasis and a larger increase in serum C reactive protein than those without it. We have also probed for the presence of IL-6 receptor by Northern blot analysis; we detected this receptor in 11 of the 43 primary renal cell carcinoma tissues but in none of the seven renal cell carcinoma cell lines. However, by use of the complementary DNA-polymerase chain reaction, the IL-6 receptor transcript was detected in all specimens, including the seven cell lines. No expression of the interleukin-3 (IL-3) gene was identified in any of the 43 primary renal cell tumors. These data provide evidence that IL-6 and its receptor may play a role in promoting the transformation and/or proliferation of renal cell carcinomas as well as in teh development of symptoms. PMID- 1749020 TI - Antineoplastic dolastatins: potent inhibitors of hematopoietic progenitor cells. AB - Dolastatins 10 and 15, isolated from the shell-less marine mollusk Dolabella auricularia, are potent antineoplastic agents with unknown myelotoxic effects in vivo. The goal of this study was to determine whether the dolastatins inhibit the proliferation of normal hematopoietic progenitor cells. Assays to test inhibition of colony formation and of cell proliferation were performed in vitro with bone marrow cell preparations enriched for progenitor cells and with progenitor cell lines, respectively, using varying drug concentrations and exposure times. Dolastatins 10 and 15 both inhibited human and murine bone marrow cell colony formation in a concentration-dependent manner, with the concentration required for half maximal inhibition ranging from 0.1 to 1 pg/mL for dolastatin 10 and from 10 to 100 pg/mL for dolastatin 15. These concentrations are 25-fold to 100 fold lower than the concentration required for antineoplastic activity. Complete inhibition of human bone marrow cell colony formation was observed at concentrations of 10-100 pg/mL for dolastatin 10 and 1000-10,000 pg/mL for dolastatin 15. Committed progenitor cells and multipotential progenitor cells were similarly inhibited. The magnitude of inhibition of human hematopoietic cell colony formation was dependent on pre-exposure time to dolastatins 10 and 15, with a reversible effect up to 8 hours and with a 24-hour preincubation resulting in maximal (100%) and irreversible inhibition. Dolastatin 10 at a concentration of 10-100 pg/mL limited the proliferation of six human and four murine hematopoietic progenitor cell lines, as measured by tritiated thymidine incorporation, to between 34% and 83% of that occurring in the absence of the drug. These results indicate that the dolastatins are potent inhibitors of normal hematopoietic progenitor cell proliferation. PMID- 1749021 TI - Time trends in incidence of brain and central nervous system cancers in Connecticut. PMID- 1749022 TI - An alternative hypothesis for bladder cancer among workers exposed to ortho toluidine and aniline. PMID- 1749023 TI - Proliferation rate in hereditary nonpolyposis colon cancer. PMID- 1749024 TI - Trauma surgery: every surgeon's specialty--presidential address, Western Trauma Association. PMID- 1749025 TI - Management of transperitoneal gunshot wounds of the spine. AB - To evaluate the results of a conservative approach to gunshot wounds of the spine with a transperitoneal trajectory, we analyzed our 4-year experience with 21 patients. The management protocol consisted of standard treatment of the intra abdominal injuries, vigorous irrigation of the missile track, and a 48-hour course of antibiotic therapy. The lumbar spine was involved in 14 patients (67%) and the thoracic spine was injured in seven (33%). Eleven patients (52%) were paraplegic on admission and ten patients (48%) had a fixed partial neurologic deficit. One patient with an ISS of 75 died intraoperatively from exsanguination (mortality, 5%). Early morbidity correlated with ISS greater than 40 and spinal AIS greater than 3. Late nonneurologic morbidity was independent of ISS and spinal AIS. One patient required reoperation for a retroperitoneal abscess secondary to a leak from a repaired ureter. Another patient had a retroperitoneal collection on a CT scan which resolved spontaneously. There were no spinal or paraspinal infectious complications in the presence (five cases) or absence of a colonic injury. No change in neurologic status was observed in any patient during a mean follow-up period of 3 months. This preliminary experience suggests that a conservative approach consisting of irrigation of the missile track and short term antibiotic therapy without laminectomy or removal of fragments from the spinal canal yields optimal results without increasing infectious complications of the spine. PMID- 1749026 TI - Acute posttraumatic renal failure: a multicenter perspective. AB - Acute renal failure (ARF) following trauma is rare. Historically, ARF has been associated with a high mortality rate. To investigate this entity we conducted a retrospective review of 72,757 admissions treated at nine regional trauma centers over a 5-year period. Seventy-eight patients (0.098%) developed acute renal failure requiring hemodialysis. Detailed demographic, clinical, and outcome data were collected. Patients with pre-existing medical conditions (group I) had a 70% increase in mortality over those without pre-existing conditions (p less than 0.004). Twenty-four patients (31%) developed ARF less than 6 days after injury (group II). The remainder (group III) developed late renal failure (mean time to first dialysis, 23 days). The predominant cause of death was multiple organ failure (82%). There were no differences in mortality because of multiple organ failure among the three groups of patients. Of the 33 survivors, six (18%) were discharged with renal insufficiency, three (9%) were discharged on dialysis, 23 (70%) were discharged home or to rehabilitation, and 27 (82%) had no significant evidence of renal insufficiency. CONCLUSION: Posttraumatic renal failure requiring hemodialysis is rare (incidence, 107 per 100,000 trauma center admissions), but the mortality rate remains high (57%). Two thirds of the cases of posttraumatic renal failure develop late and are secondary to multiple organ failure; one third of the cases of posttraumatic renal failure develop early and may result from inadequate resuscitation. PMID- 1749027 TI - Outcome for delayed operation of penetrating colon injuries. AB - It has been stated that delay in operative repair of penetrating injuries to the gastrointestinal tract will result in a high rate of complications related to infection. To test this assertion, a group of patients with penetrating injuries to the colon were analyzed who had operative repair delayed (usually because of triage considerations) more than 6 hours after admission to the hospital. Nine hundred six patients who survived at least 48 hours after injury were divided into two groups. The immediate group of 769 patients was treated within 6 hours of admission and the delayed group of 137 patients was treated more than 6 hours after admission. The mortality for the immediate group was 4.0% vs. 1.5% for the delayed group. Colon-related infectious complications, defined as abscess or colon suture-line failure, occurred in 10% of the immediate group and 4.4% of the delayed group. To eliminate the effect of associated injuries, the group of patients with colon injuries only was analyzed separately. There was no mortality for 128 patients with colon injuries only operated on within 12 hours of injury, and the colon-related infectious morbidity rate was 3%. Eleven patients with colon injuries only were treated after 12 hours with a mortality of 9% and colon related infectious morbidity of 18%. These data demonstrate that even patients with fecal contamination can have operative repair delayed for up to 12 hours without undue morbidity related to infection. PMID- 1749028 TI - Trauma management in a war zone: the Lebanese war experience. AB - Lessons learned from the Vietnam and Korean conflicts have emphasized the necessity of an organized preparedness for optimal management of casualties. The present report summarizes the experience of a tertiary care center in the present Lebanese war. Between 1975 and 1986, approximately 30,000 war casualties were treated at the American University of Beirut Medical Center (AUBMC). A disaster plan was implemented whenever more than 25 major trauma victims were received within 1 hour. In-field stabilization and emergency room (ER) thoracotomy were not employed. The results are illustrated by an analysis of 1,500 cases of abdominal trauma, (1,314 high-velocity gunshot wounds, 29 stab wounds, 157 blunt injuries). A total of 1,420 patients were operated on within 6 hours of admission and 711 within the first hour. Overall mortality was 130, 8.7%; 9.5% for gunshot wounds, 3.4% for stab wounds, and 2.5% for blunt trauma. One hundred forty-five patients or 9.7% had negative findings at laparotomy. The factors affecting mortality were hypotension on admission (26.5% for a BP less than 90 mm Hg and 2.8% for a BP higher than 90 mm Hg) and the presence of extra-abdominal injuries (14.4% with and 4.4% without). The chief causes of death were hemorrhage (3.7%), sepsis (2.1%), and ARDS (1.2%). PMID- 1749029 TI - Distal pancreatectomy for trauma: a multicenter experience. AB - During a 5-year period, 74 patients with pancreatic injuries were managed by distal pancreatic resection at nine referral trauma centers. Patient ages ranged from 4 to 72 years. Injury mechanism was blunt trauma in 34 (46%) patients, gunshot wound in 27 (36%), stab wound in 11 (15%), and shotgun blast in two (3%). There were 19 class II, 50 class III, and 5 class IV pancreatic injuries. The resection comprised up to 33% of the pancreas in 21 (28%) patients, from 34% to 66% in 45 (61%), and greater than 67% in eight (11%). The pancreatic resection margin was closed with staples in 44 (59%), silk sutures in 20 (27%), and polypropylene sutures in eight (11%). Of 32 patients in whom the spleen was uninjured, the spleen was left intact in 17 (53%). There were nine (12%) deaths. The cause of death was irreversible shock in three patients, multiple organ failure in five, and severe head injury in one. Pancreas-related complications occurred in 32 (45%) of 71 patients who survived the initial operation. Intra abdominal abscess developed in 24 patients; 11 were managed by percutaneous drainage alone. Pancreatic fistula developed in 10 patients; eight closed spontaneously from 6 to 54 days. Other pancreas-related morbidity included pancreatitis (6), pseudocyst (2), and hemorrhage (2). Exocrine insufficiency was not evident in any patient and diet-controlled hyperglycemia occurred in one individual following 80% pancreatic resection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749030 TI - Hypertonic fluid resuscitation improves cerebral oxygen delivery and reduces intracranial pressure after hemorrhagic shock. AB - Prospective clinical studies have shown that hypotension from hemorrhage contributes to increased morbidity and mortality in patients with traumatic brain injury. It is implied that poorer outcome is the result of secondary brain injury from impaired cerebral oxygen delivery (cO2del). We studied the early and late effects of hypertonic sodium lactate (HSL: 500 mOsm/L) resuscitation on mean arterial pressure (MAP), cardiac output (CO), systemic oxygen delivery (sO2del), cerebral perfusion pressure (CPP), intracranial pressure (ICP), cO2del, cerebral blood flow (CBF), serum osmolality, and cortical water content (CWC) in a porcine model of hemorrhagic shock. Swine were randomized to receive a bolus (4 mL/kg) of either lactated Ringer's solution (LR: 274 mOsm/L) or HSL after shock, followed by either LR or HSL to return MAP to baseline levels. Shed blood was returned 1 hour after resuscitation, and all animals were studied for 24 hours. Control animals were instrumented only. The HSL resuscitation significantly increased cO2del and CBF for 24 hours postresuscitation when compared with LR. The ICP in the HSL-treated animals was significantly lower throughout the postresuscitation phase when compared with the LR-treated animals (p less than 0.05). The CWC was significantly lower in the HSL-treated animals (p less than 0.05). We attribute these effects to hypertonic dehydration of both the brain parenchyma and the cerebrovascular endothelium. These data suggest that by decreasing ICP and improving cO2del after shock, HSL could decrease secondary brain injury when brain injury and shock occur together. PMID- 1749031 TI - Penetrating zone-II neck injuries in children. AB - Over a 4-year period, 1,237 children under 16 years of age were managed at our level-I pediatric trauma center, of which 24 (1.9%) had zone-II penetrating neck injuries. Six of these 24 children (25%) were explored surgically with positive findings in four and negative findings in two neck explorations; five children (21%) underwent radiologic or endoscopic studies and were observed; 13 (54%) were observed only and did not require studies or exploration. Nonoperative observation of penetrating zone-II neck injuries is safe and the procedure of choice if active observation can be performed and the facilities for immediate operative intervention are available. PMID- 1749032 TI - Minor splenic injuries: associated injuries and transfusion requirements. AB - To address criticisms of nonoperative management of splenic injury, we hypothesized that (1) patients with minor splenic injuries have a lower risk of associated visceral damage than patients with splenic injuries in general, and (2) exploration of these patients does not decrease their blood requirements. We reviewed charts of 182 patients who suffered blunt splenic trauma between 1983 and 1988. Sixty-seven sustained minor injuries, defined as requiring no therapy or responding to topical hemostatic agents. Twenty-three were initially managed nonoperatively, with three subsequently explored surgically for falling hematocrit; no associated injury requiring therapy was found. The median transfusion requirement in these 23 patients was 2 units. Forty-four were immediately explored, 11 for readily diagnosed injuries mandating laparotomy. The other 33 were explored for hemoperitoneum. One had an unsuspected bowel injury. The median blood requirement in these 33 was 2.5 units. We conclude that patients with minor splenic injuries who have no other indication for laparotomy have a very low incidence of associated significant abdominal injury. Their transfusion requirements are also not reduced by exploration. PMID- 1749033 TI - Delayed diagnosis of cervical spine injuries. AB - Over a 32-month period, the cases of all patients with multiple injuries on whom cervical spine roentgenograms (CSRs) were obtained during blunt trauma evaluation in a trauma center were reviewed to determine the incidence, outcome, and clinical consequence of delayed diagnosis of cervical spine injuries. A total of 1,331 patients had CSRs following blunt injury. Sixty-one (4.6%) of the patients had documented cervical fractures or dislocations. The patients were seriously injured (mean Trauma Score, 12; mean Glasgow Coma Scale score, 11; and mean Injury Severity Score, 30.3). Eleven of the patients died in the trauma room; 9 with fatal atlantoaxial dislocation. Of the 50 survivors (81.9%), neurologic deficits were present in 15 (30%), and 8 of those had complete spinal cord injuries. The diagnosis of the cervical spine injury was made during the initial evaluation in 56 of the 61 patients (91.8%). Five patients had delayed recognition of their cervical spine injury (2-21 days). The reason for the delay was incomplete CSRs in all patients, despite multiple views (up to 13). The missed injuries occurred in patients in whom complete visualization of the spine was most difficult (i.e., severe degenerative arthritis of the cervical spine in two patients; previous cervical fractures in one patient; instability during resuscitation in one patient). Radiologic misinterpretation occurred in one patient. The diagnosis of cervical spine injury was pursued because of persistent neck pain in two patients, and the development of subtle neurologic findings in three. The neurologic deficits in the three patients resolved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749034 TI - Management of patients with indeterminate diagnostic peritoneal lavage results following blunt trauma. AB - The management of blunt trauma victims with indeterminate diagnostic peritoneal lavage (DPL) findings remains controversial. We reviewed 1,196 patients undergoing DPL to identify patients with indeterminate DPL (red cell counts of 20,000 to 99,999 rbc/mm3). Only 4% (48%) had indeterminate DPL results. Repeat DPL (R-DPL) was performed in 31 patients. Six repeat DPLs produced positive results (greater than 100,000 rbc/mm3), 15 produced indeterminate results, and 10 produced negative results (less than 20,000 rbc/mm3). A review of the nine laparotomies performed in this group revealed only two operations that were therapeutic. Twelve patients had abdominal CT scans following indeterminate DPL. Six patients had negative CT scans and were successfully managed without operation. The findings were positive on six other CT scans. Four patients with positive CT scans, including two splenic injuries, one liver injury, and one renal laceration, were managed successfully without surgery. The remaining two patients with positive CT scans underwent laparotomy. The first had a renovascular injury diagnosed from the CT scan after negative findings on repeat DPL. The second had a minor splenic injury diagnosed from the CT scan. A subsequent repeat DPL produced a positive result prompting a nontherapeutic operation. Eleven patients were observed without repeat DPL or CT scanning. Of these, four eventually underwent laparotomy on the basis of clinical suspicion alone. Only one of these patients required therapeutic intervention at the time of laparotomy. Intra-abdominal injury was common in patients with indeterminate DPL results, however, only four (8%) of the patients required a therapeutic operation. Both negative repeat DPL results or negative findings on CT scans predicted successful nonoperative management.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749035 TI - Death and disability from agricultural injuries in Wisconsin: a 12-year experience with 739 patients. AB - During a 12-year period, 739 patients were admitted to a referral trauma center as the result of injuries incurred while farming. There were 608 (82%) male patients and 131 female patients. Ages ranged from 1 to 89 years including 160 patients (22%) less than 16 years old and 78 patients (11%) more than 65 years old. The injury mechanism was a farm animal in 225 (30%), farm machinery in 168 (23%), a tractor in 120 (16%), a fall in 77 (10%), a power take-off in 47 (7%), a cornpicker in 42 (6%), and miscellaneous in 60 (8%). There were 16 (2%) deaths attributable to the agricultural accident. Tractors were involved in eight of these deaths, falls in four, power take-offs in three, and farm machinery in one. Furthermore, 159 (22%) patients were left with significant permanent disability including orthopedic problems in 131 patients, neurologic deficits in 22, and pulmonary disability in 6. Agricultural trauma is frequent and diverse with unique injury mechanisms. Life-threatening injuries are often seen and permanent disability is common. Effective injury prevention must focus on farmer education, additional mandatory safety features on agricultural equipment, and appropriate design of rural trauma systems. PMID- 1749036 TI - Sagittally oriented fractures of the lateral masses of the cervical vertebrae. AB - Lateral flexion of the cervical spine may cause a sagittally oriented fracture of the lateral mass with shearing of all or part of the lateral mass away from the vertebral body. We report 22 patients with 24 sagittal fractures of the cervical lateral masses. Cross-table lateral roentgenograms suggested the presence of a sagittal lateral mass fracture in two thirds of the cases based upon malalignment or widening of the facet joints, displaced fracture fragments, subluxation of the spine, or rotation of the spine above the level of abnormality. However, the cross-table lateral roentgenogram was normal in one third of cases. Oblique roentgenograms were available in eight cases; these were positive in five, equivocal in one, and negative in two. Visible fracture lines, often associated with lateral displacement of part or all of the lateral mass, allowed all 24 fractures to be detected on the supine anteroposterior view films. Sagittal lateral mass fractures were unstable in 59% (13/22) of the cases; neurologic deficits, including quadriplegia, hemiplegia, and radiculopathy, were present in 45% (10/22). Computed tomography and complex-motion tomography were useful in confirming the sagittal lateral mass fracture and in detecting other associated fractures. PMID- 1749037 TI - Epidemiology of acute knee injuries: a prospective hospital investigation. AB - During a 1-year period, data on all acute injuries treated at emergency departments were entered into a registry; of these injuries, 6% involved the knee joint. The patients were followed until a definite diagnosis was established. The rate of anterior cruciate ligament injuries and meniscus tears was, respectively, 0.3 and 0.7 (injuries per 1,000 inhabitants per year). The rate of dislocations of the patellofemoral joints was equal to the rate of anterior cruciate ligament injuries. Ten percent of the cases involved ligament injuries, and isolated ruptures of the anterior cruciate ligaments were twice as common as combined lesions of this ligament. Injuries of both the collateral ligament and the meniscus represented 6% of the cases. In most age groups male patients predominated, but the frequency of anterior cruciate ligament injuries was similar in both sexes, while the frequency of collateral ligament injuries and meniscus tears varied according to both gender and age. Only 27% of the injuries were associated with sports activities, but they were found twice as often among athletes than people injured in nonathletic accidents. Ruptures of the collateral ligament and anterior cruciate ligament were four and seven times more common among athletes, respectively, while athletes sustained fewer meniscus tears than people involved in nonathletic activities. Half of the patients needed further care after primary treatment, and 18% were primarily (65%) or secondarily (35%) admitted to in-patient care. Operative treatment, including arthroscopic examination, was performed in 20% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749038 TI - Early experience with the gamma interlocking nail for peritrochanteric fractures of the proximal femur. AB - Surgical fixation, early weight-bearing, and bony union remain a challenge in the treatment of peritrochanteric femur fractures, especially if the fractures are comminuted or unstable. Preliminary experience with the Gamma locking nail, a short intramedullary nail connected to a sliding compression screw augmented with distal locking screws, is presented. In a consecutive series of 29 patients, all fractures were adequately reduced and immediate weight-bearing was begun regardless of fracture configuration (13/27 fractures classified as unstable). Twenty-seven patients were reviewed at 6 months. At follow-up, all patients continued to be ambulatory and all fractures healed. Major complications included screw migration in the femoral head (two patients), difficulty in securely placing the distal screws (eight patients), and a femoral shaft fracture through the distal locking screws following a fall. The technical problems inherent in the device and its instrumentation are discussed. In this early experience, the Gamma nail appears to allow for early patient ambulation regardless of the fracture configuration with excellent clinical results. PMID- 1749039 TI - Distal femoral nonunion treated with interlocking nailing. AB - From December 1986 to September 1989, 24 consecutive cases of distal femoral nonunion in adults were treated with Grosse-Kempf interlocking nailing and prospectively followed for an average of 32 months. The union rate was 91.7% (22/24) with a union period of 4.5 +/- 1.8 months. Complications occurred in two patients (8.3%), who suffered nonunion because of implant failure. A cast brace is very useful in promoting ambulation and reducing early overactivity. The potential for implant failure is a result of a concentration of stress over the nail hole, with the most stress occurring near the fracture site (p less than 0.05). PMID- 1749040 TI - Interleukin 6--a potential mediator of lethal sepsis after major thermal trauma: evidence for increased IL-6 production by peripheral blood mononuclear cells. AB - We studied the plasma levels of the acute phase mediator interleukin 6 (IL-6) in 21 severely burned patients (burn injuries ranging from 24% to 75% total body surface area). The posttraumatic course of the IL-6 plasma levels was closely related to the clinical outcome. The nonseptic survivors as well as survivors with suspected sepsis (n = 14) exhibited maximal amounts of IL-6 (251 +/- 32 pg/mL) during the first 3 days post-burn, which subsequently returned to values within the normal range (days 30 to 50; 26 +/- 8 pg/mL). In the nonsurvivors (n = 7) IL-6 concentrations permanently increased (up to 1,921 +/- 356 pg/mL) until death (days 10 to 19) resulting from sepsis with consecutive multiple organ failure. Peripheral blood mononuclear cells (PBMCs) of patients expressed IL-6 specific mRNA in vivo at high levels in contrast to the PBMCs of healthy donors. In addition, the spontaneous and PHA-induced in vitro production of IL-6 by patients' PBMCs was enhanced compared with healthy controls, whereas no significant differences were obtained with bacterial endotoxin (LPS). The findings suggest that interleukin 6 is a potential mediator of lethal sepsis after major thermal trauma. PMID- 1749041 TI - Angiographically placed balloons for arterial control: a description of a technique. AB - Obtaining proximal and distal control is essential in the repair of arterial injuries. Occasionally, the location of the injury makes this difficult, risks excessive blood loss, or requires wide exposure to obtain control. Recently, we have used percutaneously placed balloons as an aid to vascular control in 11 patients who had arterial injuries identified angiographically. The balloon is placed under fluoroscopic guidance and is then deflated. The balloon is reinflated intraoperatively at the time vascular control is needed. Five balloons were placed for inflow control in patients with very proximal subclavian artery injuries. All were then able to undergo successful repair through a limited supraclavicular incision without sternotomy or thoracotomy. Two were placed in the internal carotid artery to obtain distal control in injuries located at the base of the skull. Both injuries were then repaired without problems. Two patients had balloons placed for external iliac artery injuries located at the inguinal ligament, one for proximal and one for distal control. Both injuries were then repaired through a limited incision. Two additional patients who had arterial injuries identified began to bleed massively while in the angiography suite. Balloons were placed proximally to control bleeding during transport and dissection. There were no complications from balloon placement. All balloons functioned well, greatly limited blood loss, and allowed for repair through a limited incision. We feel this is a technique that can be utilized in selected cases of angiographically identified arterial injuries in which operative exposure is likely to be difficult, cause significant blood loss, or require an extensive incision and dissection. PMID- 1749042 TI - Plastic deformation of the forearm: a review and case reports. AB - Plastic deformation of long bones can occur in any age group but it is more common in children. Based on our experience with this condition and the suggested guidelines for treatment in the literature, we believe that significant deformity (15 degrees or more) in children over 10 years of age should be manipulated and corrected. In children 6 to 10 years of age, attempts should be made to correct a severe deformity (20 degrees or more). Children under 5 years of age probably require no treatment, since remodelling most likely will restore the correct anatomy and function. PMID- 1749043 TI - Radial neck fracture complicating closed reduction of a posterior elbow dislocation in a child: case report. AB - A case of radial neck fracture complicating repeated attempts at closed reduction of a posterior elbow dislocation in a child is described. This case underscores the necessity of using proper technique when reducing posterior elbow dislocations. The mechanism of radial neck fracture in association with posterior elbow dislocation is discussed. PMID- 1749044 TI - Bilateral traumatic anterior/posterior dislocations of the hip joints: case report. AB - A case of simultaneous traumatic bilateral anterior/posterior hip dislocations in a 28-year-old man is presented. The mechanism and treatment of this injury, as well as its complications, are discussed. PMID- 1749045 TI - Posttraumatic meningococcal meningitis: case report. AB - A case is described of fulminant meningococcal meningitis occurring 1 day after serious head and facial trauma. Although meningococcus is one of the most common causes of bacterial meningitis in general, it is distinctly rare as a cause of posttraumatic meningitis. A review of the literature is included. PMID- 1749046 TI - Isolated injury of the coracoid process: case report. AB - Injuries of the coracoid process are generally rare in traumatic injuries of the shoulder. To our knowledge, there have been fewer than 12 cases of isolated injury of the coracoid process reported in the world literature. We present a case of isolated injury to the coracoid process and discuss its significance. PMID- 1749047 TI - Hepatic duct disruption from blunt abdominal trauma: case report and literature review. AB - A laceration-avulsion injury of the hepatic duct from blunt trauma is described. Operative findings rather than preoperative studies led to the correct diagnosis. A combination of suture repair, left hepatic duct ligation, and hepaticojejunostomy were used to primarily manage this complex injury. Postoperative hepatobiliary scintigraphy and clinical follow-up over 1 year demonstrate satisfactory biliary drainage. Principles of the management of hepatic duct injury are reviewed. PMID- 1749048 TI - Rupture of the flexor tendon secondary to osteoarthritis of the pisotriquetral joint: case report. AB - Attrition ruptures of the flexor tendons in the carpal tunnel are uncommon. A case of rupture of the flexor digitorum profundus tendon to the little finger secondary to osteoarthritis of the pisotriquetral joint is reported. Mechanical attrition against the radial side of the pisiform was thought to be responsible for the rupture. PMID- 1749049 TI - Chronic neuropsychological and neurological impairment following acute exposure to a solvent mixture of toluene and methyl ethyl ketone (MEK). AB - A 38 year-old laborer experienced solvent intoxication during each of two spray paintings of a dump truck and other heavy equipment in an enclosed, unventilated garage. The paint base consisted primarily of toluene and methyl ethyl ketone. Nausea, headaches, dizziness, respiratory difficulty and other symptoms began after exposures. Over the next several days he developed impaired concentration, memory loss and cerebellar signs including an intention tremor, gait ataxia and dysarthria. MRI of the brain and EGG early in the work-up were normal, although later MRIs demonstrated fluid collection over the left parietal area. Examination by a toxicologist and neurologist revealed likely toxic encephalopathy with dementia and cerebellar ataxia. Three formal neuropsychological assessments over 2 1/2 years quantified cognitive, motor and behavioral changes. Despite similar findings in chronic exposure to these solvents, lasting sequelae following acute exposure have not been widely reported. PMID- 1749050 TI - Acetonitrile serum concentrations and cyanide blood levels in a case of suicidal oral acetonitrile ingestion. AB - Acute acetonitrile toxicity is mainly dependent on the release of cyanide via hepatic metabolism. Although evaluated in animals, few data are available concerning the toxicokinetic parameters of acetonitrile and acetonitrile liberated cyanide in human. This paper reports a case of suicidal oral acetonitrile ingestion of about 5 mL without severe symptoms of intoxication in a previously healthy adult male with a body weight of 60 kg. Acetonitrile serum concentrations as well as cyanide blood levels were determined over the whole hospitalization. The elimination half-lives calculated from these data were 32 h for acetonitrile and 15 h for cyanide. After sodium thiosulfate bolus application, the cyanide blood level rapidly decreased to 10% of the initial value, indicating that sodium thiosulfate sufficiently detoxifies acetonitrile liberated cyanide. Since cyanide levels again increased to maximal values about 4.5 h after sodium thiosulfate application, continued thiosulfate therapy is required as predicted by the long elimination half-lives of acetonitrile and acetonitrile-liberated cyanide. Determination of cyanide and acetonitrile concentrations is recommended for the estimation of optimal individual sodium thiosulfate dosage. PMID- 1749051 TI - Mushroom poisoning in the United States--an analysis of 1989 United States Poison Center data. AB - An analysis of mushroom case exposures reported in 1989 to the American Association of Poison Control Centers "National Data Collection System" by poison centers in the United States was conducted to obtain a clearer view of mushroom poisoning epidemiology and outcome in the United States. PMID- 1749052 TI - Toxicity after self-poisoning by ingestion of potassium chloroplatinite. AB - A 31 year-old man ingested 10 mL of a photographic toning solution containing 600 mg of potassium chloroplatinite in a suicide attempt. Subsequent toxic effects included acute oliguric renal failure, metabolic acidosis, fever, muscle cramps, gastroenteritis and rhabdomyolysis. Laboratory abnormalities included mildly elevated liver enzymes and elevated peripheral blood neutrophil and eosinophil counts. All symptoms and signs of toxicity resolved over a six day hospital stay with supportive medical management only; thereafter he was lost to medical follow up. A spot serum platinum concentration was 245 mcg/dL and a spot urine platinum concentration was 4200 mcg/L. PMID- 1749053 TI - Normal fetal outcome after maternal ciguateric toxin exposure in the second trimester. AB - A case of a severe episode of ciguatera poisoning in a mother during the second trimester is presented. The mother experienced an increase of fetal movements one hour after the poisonous meal. She endured multisystemic symptoms typical of ciguatera for eight weeks. The presence of ciguatoxin in the fish was confirmed by immunoassay and two bioassays. The newborn at term was normal with adequate respiratory and neurological reflexes. The child developed normally in his first 10 months. This is in contrast with another report of a mother exposed to ciguatoxin at term who delivered an infant suffering from facial palsy and possible myotonia of the hands. Dose and gestational timing may explain these observed differences. PMID- 1749054 TI - Toxic neonatal effects following maternal clomipramine therapy. AB - Clomipramine is a chlorinated tricyclic antidepressant commonly used in the treatment of depression (1). The drug is widely prescribed in Europe and Canada and has been recently approved for use in the USA. Its safety during pregnancy and breastfeeding, however, has not been fully established. Very few reports on its effect on the fetus and neonate have been published (2,3). We report a case of a mother treated with clomipramine during pregnancy, and the side effects observed in the infant. The correlation between plasma clomipramine concentrations in the baby's blood and clinical effects are described. Subsequently, we present the pregnancy outcome of five prospectively collected cases. PMID- 1749055 TI - Philodendron/dieffenbachia ingestions: are they a problem? AB - Ingestions involving the philodendron/dieffenbachia members of the Arum family are allegedly associated with the development of intense irritation of mucous membranes, resulting in swelling of the tongue, lips and palate. Although numerous literature citations promote their toxicity, there are few case reports which substantiate a cause-effect relationship between ingestion and resultant symptomatology. To assess the toxic manifestations associated with the ingestion of these plants, a retrospective review of such cases reported to a Regional Poison Information Center was performed. 188 cases were identified and the integrity of the leaf had been broken in all cases. Philodendrons accounted for 67.5% and dieffenbachias for 32.5% of the cases. 72.8% involved children aged 4 12 months. Only 2.1% (4) of the patients were symptomatic (dieffenbachia-3; philodendron-1). In all cases, the symptoms occurred within 5 minutes of the exposure and were of short duration and the outcome was classified as minor. In this 24 month senses of 188 exposures, severe oral complications and the delayed development of symptoms were not observed. PMID- 1749056 TI - Diagnosis of snake venoms by a reverse latex agglutination test. AB - A reverse latex agglutination test using protein A column purified rabbit antivenom IgG-sensitized latex particles was developed for the detection of the six medically important snake venoms of Thailand. The detection limit of the reverse latex agglutination test was 0.16 to 1.2 micrograms/mL of crude venoms. Cross-reactions with heterologous venoms were observed at concentrations 460 to 16000 times that of homologous venoms. Detection of various snake venoms in clinical specimens was carried out by the reverse latex agglutination test. The sensitivity was 52.5% of the 59 serum samples. There was one (1.69%) false positive sample. The positive detection of venom in wound swabs (26 cases) was 38.5% and was not statistically different from that observed in paired serum samples. Interference from human plasma, serum and urine on the reverse latex agglutination test could be eliminated by adsorption with normal rabbit IgG coated latex suspension or by heat inactivation at 56 degrees C for 30 min. Prozone effect observed in some sera was eliminated by heat inactivation at 56 degrees C for 30 min. The sensitized latex particles were stable at 4 degrees C and -20 degrees C for at least 3 months. Cycles of freezing-thawing and lyophilization did not change their reactivities. The total test time was about 40 min. PMID- 1749057 TI - Rhabdomyolysis after suicidal ingestion of an overdose of caffeine, acetaminophen and phenazone as a fixed-dose combination (Spalt N). AB - Rhabdomyolysis without renal failure was noted after suicidal ingestion of 29 tablets of Spalt N containing 7.25 g of acetaminophen, 7.25 g of phenazone and 1.45 g of caffeine by a 29 year-old weighing 73 kg. The maximum serum creatine kinase was 1920 U/L, serum myoglobins were 49 to 167 ng/mL. Acetaminophen, phenazone and caffeine were quantified and identified in serum by gas chromatography and gas chromatography/mass spectrometry. It is suggested that rhabdomyolysis might have been caused by caffeine. PMID- 1749058 TI - Flumazenil for the reversal of refractory benzodiazepine-induced shock. AB - Benzodiazepines are known to cause central nervous system and centrally mediated cardiovascular depression. The benzodiazepine antagonist flumazenil has been shown to antagonize benzodiazepine-induced central nervous system depression. We report a case in which cardiovascular depression secondary to benzodiazepine use was reversed by this agent. PMID- 1749059 TI - Poison center numbers. PMID- 1749060 TI - Adverse drug reaction. PMID- 1749061 TI - Cocaine Abuscreen in the emergency room. PMID- 1749062 TI - Nutritional adjustments in response to reproductive stresses within Guatemalan women. PMID- 1749064 TI - Maternal malnutrition and breastfeeding: is there really a choice for policy makers? PMID- 1749063 TI - Influences of maternal nutrition and lactation on length of post-partum amenorrhoea. PMID- 1749065 TI - The implications of poor maternal nutritional status during pregnancy for future lactational performance. PMID- 1749066 TI - Treatment of torsade de pointes with intravenous magnesium in idiopathic long QT syndrome. AB - A middle aged woman with idiopathic long QT syndrome was found to have repetitive ventricular tachycardia of the "torsade de pointes" type. The arrhythmia was resistant to mexiletine and lidocaine, but was controlled by intravenous magnesium sulfate (MgSO4). The recurrent attacks were abolished by a bolus of 2.0 g MgSO4, and extremely prolonged QTU interval was reduced by intravenous infusion of 5 mg/min MgSO4 for 36 h. This case shows the effectiveness of intravenous magnesium in controlling the attack of torsade de pointes in patients with idiopathic long QT syndrome. PMID- 1749067 TI - Transient segmental asynergy of the left ventricle of patients with various clinical manifestations possibly unrelated to the coronary artery disease. AB - Eight cases of transient reversible segmental asynergy of the left ventricle thought not to be related to coronary artery lesions are reported. Three cases were associated with inflammatory reactions of unknown origin, and one each with lactic acidosis, abdominal surgery, hypoglycemia, tetanus and pneumonia. None of the patients had symptoms suggestive of ischemic heart disease before or after these episodes. Electrocardiograms before these episodes were all normal. Two dimensional echocardiography was performed to evaluate abnormal electrocardiograms. Coronary angiography was performed in 4 of 8 cases and was normal in all 4 cases; 2 done as emergencies and 2 non-emergencies. Two ergonovine tests were negative. Left ventricular wall motion abnormalities, present mainly at the apex of the left ventricle, returned to normal in 1 to 4 weeks. Giant negative T waves in the chest leads during this recovery period were characteristic electrocardiographic features and normalized in 6 weeks on average. We believe that these episodes were not related to ischemia due to coronary artery disease, but to some metabolic humoral factors. An excellent prognosis can be expected if these abnormal metabolic circumstances can be resolved. PMID- 1749068 TI - Hemodynamic efficacy of E-1020 in comparison with dopamine on acute mitral regurgitation in anesthetized dogs. AB - To evaluate the effects of a new phosphodiesterase inhibitor, E-1020 (1, 2 dihydro-6-methyl-2-oxo-5-(imidazo [1, 2-a] pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate), on cardiovascular hemodynamics in acute heart failure, we compared its effects with those of dopamine on experimentally produced acute mitral regurgitation in dogs. After the production of mitral regurgitation by transmyocardial chordal sectioning and obtaining a stable state, dopamine (5 micrograms/kg/min) was infused until the peak positive dP/dt (peak (+) dP/dt) increased to about 50% of the predopamine value. After complete recovery, E-1020 (30 micrograms/kg) was infused over 5 min and the data were obtained 10 min later. Both drugs equally increased peak (+) dP/dt, decreased systemic vascular resistance, and increased cardiac output. Left ventricular (LV) end-diastolic pressure, LV end-diastolic segment length (EDL), and mean left atrial (LA) pressure decreased with both drugs. The changes in EDL and mean LA pressure were larger with E-1020 than with dopamine (p less than .01 and p less than .05). Although mean inferior vena caval blood flow volume (mIVCF) increased and mean inferior vena caval pressure decreased with both drugs, the increment of mIVCF was smaller with E-1020 (p less than .001). Thus, E-1020 had not only a positive inotropic effect but also a vasodilatory action both on resistance vessels and on capacitance vessels. PMID- 1749069 TI - XeCl excimer laser-induced fluorescence for selective ablation of atheromatous tissue. AB - In order to develop a reliable laser-induced fluorescence (LIF) guided laser angioplasty system, real time, pulse-by-pulse fluorescence spectra were recorded and the same fiberoptic was used for both detection of the fluorescence and for atheromatous tissue ablation. A 308 nm XeCl excimer laser served as the laser source for both the induction of fluorescence and the ablation. The fluorescence signal was induced at high laser energies during ablation without any serious change in the fluorescence pattern. A new characteristic fluorescence peak at 540 nm for atheromatous tissue was observed after treatment with chlortetracycline hydrochloride (CTC). This allowed the development of an algorithm and a subsequent index to discriminate the atheromatous tissue from the normal tissue. During atheromatous tissue ablation, this index changed as normal tissue was approached, thereby avoiding vessel perforation. Our results suggest that monitoring of this index through the catheter delivering the laser energy enhances selective ablation while simultaneously reducing the risk of vessel perforation. PMID- 1749070 TI - Contribution of calcium-activated neutral protease to the degradation process of ischemic heart. PMID- 1749071 TI - Neutrophil-induced myocardial cell damage and active oxygen metabolites. AB - Free radicals derived from polymorphonuclear leukocytes (PMN) have been suggested to play an important role in myocardial ischemia-reperfusion injury. To define the mechanism by which activated PMN exacerbate ischemic myocardial damage, we investigated the extent of cell injury, free radical generation and lipid peroxidation in embryo mouse myocardial cells co-incubated with activated PMN. The generation of free radicals derived from PMN correlated with the extent of myocardial cell injury. Among the cell sheets preconditioned with hypoxic and glucose free medium, PMN-adhered myocardial cells were initially injured after adding PMN activator, extending to adjacent cells. Chemiluminescence emission and thiobarbituric acid reactive substance in the co-incubated cells were markedly increased and sustained compared with those in each cell monoincubation. The augmented lipid peroxidation was related to the progression of myocardial cell injury. These results indicate that PMN-derived free radicals cause membrane disruption, contributing to the progression of myocardial injury. PMID- 1749072 TI - Cardiac muscle cell damage through autoimmune mechanism--can cardiac proteins provoke autoimmune myocarditis? AB - In this paper, the ability of human cardiac myosin to provoke autoimmune myocarditis was investigated. Myosin fractions were immunized into A.SW. mice, Lewis rats or Hartley guinea pigs. All of the immunized rats displayed overt symptoms of myocarditis and, in a few cases, died from it. The hearts of these rats were enlarged and discolored. Histologically, the muscles of the heart were characterized by remarkable cell infiltration, extensive myofiber necrosis and the appearance of polynuclear giant cells. Neither mice nor guinea pigs showed such disease profile. In this novel experimental model, the disease state was transferable by T lymphocytes. Thus, cardiac myosin was shown to provoke muscle cell damage through a T cell mediated autoimmune process. PMID- 1749073 TI - Mitochondrial DNA mutations and disturbances of energy metabolism in myocardium. AB - Since mitochondria occupy a pivotal position in energy metabolism, mitochondrial dysfunction is directly linked with disturbances in cellular function. Mitochondria possess their own DNA, which codes 13 subunits of the mitochondrial energy transducing system; the other subunits are coded by nuclear DNA. Recent advances in gene technology, especially the polymerase chain reaction (PCR), permit us to analyze mitochondrial DNA mutations in a small quantity of tissue. We devised rapid and accurate methods to detect mitochondrial DNA mutations, i.e., the primer shift PCR method and the PCR-Southern method. We also developed a method to determine DNA sequences directly without cloning. Using these methods, we revealed that multiple mitochondrial DNA mutations exist in the myocardium of patients with cardiomyopathy. One mutation was based on the following directly repeated sequence: 5'-CATCAACAACCG-3'. This sequence exists in both the ATPase6 gene and the D-loop region, and pseudo-recombination occurs at that directly repeated sequence resulting in a 7.4 kbp deletion. Accordingly, some subunits of the mitochondrial energy transducing system can not be biosynthesized by these deleted mitochondrial DNA, and energy transduction is substantially depleted. Even without reduction of blood supply, mitochondrial DNA mutations can induce a chronic ischemia-like state in the myocardium, which might be a factor in the genesis of cardiomyopathy. PMID- 1749074 TI - [Recent progress of Pseudomonas aeruginosa infections; pathological mechanisms of new toxic metabolites]. PMID- 1749075 TI - [Refractory infection with Pseudomonas aeruginosa and the trend of clinical studies]. PMID- 1749076 TI - [Methods for isolation, identification and serotyping of Pseudomonas aeruginosa]. PMID- 1749077 TI - [Virulence factors of Pseudomonas aeruginosa in mice]. PMID- 1749078 TI - [Role of phagocytes in pseudomonal infections]. PMID- 1749079 TI - [Mechanism of susceptibility and resistance of Pseudomonas aeruginosa to aminoglycosides]. PMID- 1749080 TI - [Mechanism of susceptibility and resistance of bacteria to beta-lactam antibiotics]. PMID- 1749081 TI - [Chemical structure, anti-bacterial activity and pharmacokinetics of cephems]. PMID- 1749082 TI - [Chemical structure, anti-bacterial activity and pharmacokinetics of monobactams]. PMID- 1749083 TI - [Carbapenems as antibiotics against Pseudomonas aeruginosa]. PMID- 1749084 TI - [Chemical structure, anti-bacterial activity and pharmacokinetics of aminoglycosides]. PMID- 1749085 TI - [Pseudomonas aeruginosa infections of airway]. PMID- 1749086 TI - [Pseudomonas aeruginosa pneumonia]. PMID- 1749087 TI - [Mucoid Pseudomonas aeruginosa infection in cystic fibrosis]. PMID- 1749088 TI - [Respiratory infections by Pseudomonas aeruginosa in the elderly]. PMID- 1749089 TI - [Pseudomonas aeruginosa bacteremia]. PMID- 1749090 TI - [Pseudomonas infection of severe burn patient]. PMID- 1749091 TI - [Pseudomonas aeruginosa infections in children]. PMID- 1749092 TI - [Pseudomonas corneal ulcer]. PMID- 1749093 TI - [Chronic otitis media infected with P. aeruginosa]. PMID- 1749094 TI - [Trend of resistant Pseudomonas aeruginosa from field of clinical laboratory medicine]. PMID- 1749095 TI - [Changing resistance of Pseudomonas aeruginosa isolates from patients with respiratory tract infections]. PMID- 1749096 TI - [Urinary tract infection caused by Pseudomonas aeruginosa]. PMID- 1749097 TI - [Pseudomonas aeruginosa ocular infection]. PMID- 1749098 TI - [Prophylactic effects of Pseudomonas aeruginosa vaccine on patients with chronic pulmonary disease]. PMID- 1749099 TI - [Vaccine therapy against Pseudomonas aeruginosa]. PMID- 1749100 TI - [Pseudomonas multicomponent vaccine in major burn patients]. PMID- 1749101 TI - [Generation and protective activities of human monoclonal antibodies against Pseudomonas aeruginosa]. PMID- 1749102 TI - [Therapeutic human monoclonal antibodies directed to Pseudomonas aeruginosa]. PMID- 1749103 TI - [Functional image of local cerebral circulation using digital subtraction angiography]. PMID- 1749104 TI - [A trend of molecular approaches to the mechanism of cancer metastasis]. PMID- 1749105 TI - [On the mechanisms of retardation of aging and inhibition of mammary tumorigenesis by energy restriction in SHN/C3H F1 female mice]. AB - Although it has long been known that energy restriction (ER) inhibits tumors and retards aging in rats and mice, its mode of action remains unknown. In rodents, ER alters the rate of age-related changes in physiological indices. Thus, it affects a broad array of age-sensitive parameters. However, present evidence does not indicate which parameters are primary contributors to the deceleration of aging. Compared to fasting or short-term underfeeding, little is known about the metabolic effects of long-term, life-prolonging ER. We thus investigated the effects of ER on hepatic enzyme activities, including drug-metabolizing enzymes and antioxidant enzymes such as superoxide dismutase and catalase. The catalase activity was found to be higher in ER mice than in control mice both at 12 and 24 months of age. In accord with the high catalase activity, lipid peroxidation in liver was much less in ER mice than in age matched control mice. beta Naphthoflavone, known to induce P-450 related enzymes and xanthine oxidase, was given (ip) to increase lipid peroxidation. The ER was found to inhibit lipid peroxidation after beta-naphthoflavone treatment. It was, therefore, concluded that long-term life-prolonging ER increases antioxidant defence, supporting indirectly the free radical theory of aging. It is well known that ER delays puberty in rodents and has a profound influence on serum hormone levels, including those of prolactin (PRL) and thyroid hormones. However, it remains unknown how these effects are produced by ER. We therefore investigated the effects of ER on the islets of Langerhans in the pancreas and on the pituitary ovarian axis. In the islets of Langerhans, ER was found to increase the density of alpha-cells significantly both in 11- and 67-week-old mice. In the pituitary gland in ER mice, the cellular density of PRL-producing cells diminished significantly while that of growth-hormone-producing cells did not. One of the modes of action of ER on the endocrine system is thus concluded to be mediated by changing cellular population. Since ER decreased PRL-producing cells and PRL plays a key role in mammary tumorigenesis, we investigated whether ER decreased the gene expression of mouse mammary tumor virus (MMTV) in SHN/C3H mice. The SHN strain, which was found to have a new MMTV provirus locus, mtv-4, was used in the study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1749106 TI - [Carcinogenic heterocyclic amines in the environment]. AB - The purpose of this report is to summarize data on carcinogenic heterocyclic amines mainly from the aspect of environmental medicine. Since 1977, a new series of heterocyclic amines has been isolated as potent mutagens and they have been shown to be carcinogenic to experimental animals. Among these carcinogens, carcinogenic amino-alpha-carbolines and amino-gamma-carbolines are widely distributed in such components of the environment as airborne particles, rain water, cigarette smoke, diesel exhaust particles and cooked foods. Moreover, most carcinogenic heterocyclic amines are reported to be present in cigarette smoke. These facts suggest that carcinogenic heterocyclic amines are likely to be ubiquitous environmental pollutants. These results also support the hypothesis that carcinogenic heterocyclic amines may be formed through combustion of various materials such as food, grass and petroleum. PMID- 1749107 TI - Effects of the consumption of cigarettes, alcohol and foods on serum concentrations of carotenoids, retinol and tocopherols in healthy inhabitants living in a rural area of Hokkaido. AB - The relationship between serum concentrations of carotenoids, tocopherols and retinol and the consumption of cigarettes, alcohol and foods was investigated in 835 healthy inhabitants (aged 35-79 years) of a rural area of Hokkaido. Serum concentrations of beta-carotene (BC), alpha-carotene (AC), lycopene (LY), beta cryptoxanthin (BX), zeaxanthin (including lutein, ZX), canthaxanthin (CX) and beta-tocopherol (including gamma-tocopherol, BT) were higher in females than in males, while serum retinol (RE) concentrations were lower. Serum alpha-tocopherol (AT) concentrations were the same for both sexes. The serum values of BC, BX, AC, LY and ZX for males were inversely associated with the consumption of cigarettes in multiple-regression analysis. The serum values of BC, AC and BX for males were inversely associated with alcohol consumption, while serum RE values were positively related to alcohol consumption for both sexes. There were significant relations between serum values of BC, AC, and ZX and the intake frequencies of carrots, tomatoes, milk and/or green-leaf vegetables, especially for females, and between serum BX values and the intake of oranges, juices and fruits. Serum RE and AT concentrations were not associated with any food intake, and BT concentrations were associated with the intake of tomatoes and juices for males. PMID- 1749108 TI - [Changes of peripheral blood parameters in aerobic dance instructors after aerobic dance instruction]. AB - To investigate the biological load of aerobic dance instruction on the body, a blood biological study was performed on 13 female instructors. The values were compared with 10 female healthy controls. The results obtained were as follows. 1. A significant negative correlation was observed between the total experience of aerobic dancing (in years) and the levels of serum phospholipids. In addition, the numbers of white blood cells and the levels of serum phospholipids, lipoperoxide, uric acid and creatinine were significantly related to aerobic dance instruction time (years). 2. The levels of serum CPK, aldolase, GOT, BUN and creatinine in the aerobic dance instructors were significantly higher than those in the controls. 3. The levels of serum CPK, uric acid, BUN, creatinine and Ca increased significantly after an intermediate class lesson (about 60 minutes). In addition, the numbers of white blood cells also increased after the lesson, but not significantly. Moreover, Significant decreases of the mean corpuscular volume and serum Mg were observed after the lesson. PMID- 1749109 TI - [The effect of sharing medical costs for the aged 70 or more on the financial balance of the health insurance society]. AB - The rapid increase of the proportion of older persons in society has made the problem of medical costs more important. Although medical cost-sharing for those aged 70 or more is decided by their medical costs and by the current proportion of such persons in the Society, it is not constant throughout the Society. The study evaluated the contribution ratio of medical cost-sharing for those aged 70 or more to the financial balance of the Society. In addition, characteristics of the Society associated with medical cost-sharing for those aged 70 or more were analyzed. The results are as follows. 1) Medical cost-sharing for those aged 70 or more was the greatest factor in the financial balance of the Society with a contribution ratio of as much as 55.2%. 2) Multiple regression analysis disclosed that dependent ratio, the average monthly salary, the area, the rate of those aged 70 or more and the average age of the Society members are significant in medical cost-sharing for those aged 70 or more. 3) Dependent ratio and the average monthly salary are the most important characteristics among those associated with medical cost-sharing for those aged 70 or more. A higher dependent ratio and a lower average monthly salary are related to higher cost sharing. This is also related to geographic factors as cost-sharing in western Japan is higher than in eastern Japan. The lower rate of those aged 70 or more and the higher average age of the Society members are related to the higher cost sharing. PMID- 1749110 TI - [A study on urinary tin in healthy adults: relationship between the concentration of urinary tin and life style]. AB - The concentrations of urinary tin in healthy adults in Aichi prefecture were determined by anodic stripping voltammetry over a period of three years (1986 1988), to obtain the normal tin level in urine and to elucidate the influence of environmental alterations on health conditions in the future. In addition to the above-mentioned method, the relationship to life style, dietary habits, smoking habits and living environment were studied, and the following results were obtained. 1) The mean +/- standard deviation of urinary tin levels for males was 3.7 +/- 2.2 (micrograms/g creatinine), and 5.9 +/- 3.0 (micrograms/g creatinine) for females. The data showed logarithmic normal distributions in both sexes, and the mean concentration for females was significantly higher than that for males (P less than 0.001). The levels of urinary tin concentrations significantly increased according with age. 2) Significant correlations of urinary tin concentrations between two observations were noticed in repeated by observed subjects. 3) As to the dietary habits, fish intake increased the urinary tin concentration, but no definite association with canned-food intake was observed. 4) Smoking habits and living environment also showed a tendency to increase the urinary tin concentration, but the difference was not statistically significant. PMID- 1749111 TI - [Study on digestibility and energy availability of daily food intake (Part 4. Shiitake mushroom)]. AB - The digestibilities of nutrients and energy in Shiitke mushrooms (Lentinus edodes) was measured in healthy adult males. A test diet was given for 5 days after 5 days on a basal diet which supplied 40g/day of protein and 45kcal/kg/day of energy. The test diet was identical with the basal diet except that shiitake was incorporated. Digestibility was calculated by the difference of fecal output between the test period and the basal period. The results obtained were follows: 1. Shiitake 60g/day intake level Digestibility of protein was 69.3 +/- 11.2%. Digestibility of fat was 66.6 +/- 24.9%. Digestibility of carbohydrate was 55.7 +/- 10.5%. The ratio of the total available energy to intake energy (Net Energy Availability) was 55.4 +/- 15.4%. 2. Shiitake 40g/day intake level Digestibility of protein was 85.5 +/- 23.8%. Digestibility of fat was 70.0 +/- 90.1%. Digestibility of carbohydrate was 65.8 +/- 13.1%. The ratio of the total available energy to intake energy (Net Energy Availability) was 67.4 +/- 25.9%. PMID- 1749112 TI - [Correlation between odor thresholds and saturated vapor pressures of odorants]. AB - The purpose of our work is to develop an estimation method for odor thresholds on the basis of physicochemical properties of odorous compounds. In this report, we examined the correlation between odor thresholds (Cth) and the saturated vapor pressures (Pvp) of various odorants. Results. 1) There were very good correlations between Pvp and k. k represents an indicator of lipid affinity. In our earlier report, k was obtained by the analysis of the gas chromatography with a column packed with a support coated by a phospholipid. Accordingly the correlations show that Pvp may be an indicator of solubility into the lipid phase. 2) It was found that correlations between Pvp and Cth were very good in several homologous series of aliphatic compounds. However ionized substances, such as acids and amines, and sulfur compounds had no good correlations. 3) In odorants having more than 3-5 carbon atoms, odor thresholds of normal types were higher than those of iso types. 4) In the series of amines, the relationship between Cth and Pvp depended upon the length and the number of alkyl chains combined with the contained nitrogen atom. 5) In the series of alcohol and aldehyde, the decrease of Cth in the rate became smaller with the decrease of Pvp. PMID- 1749113 TI - Lifestyle and the right to clean air in public places (RCA) (Part 3). Relationship between opinions concerning RCA and personal lifestyle. AB - As a preliminary study to evaluate the possible roles of health education (education to acquire a healthy lifestyle) in supporting the development of a smokeless society, the relationship between opinions concerning the right to clean air in public places (RCA) and personal lifestyle as well as the relationships among three aspects of RCA and personal lifestyle were investigated in a randomly-selected sample (n = 887) of a population using a self-administered questionnaire. Relationships between opinions concerning RCA and lifestyle were analyzed within four subgroups of subjects defined by smoking status and sex. The results of these analyses indicated that opinions concerning RCA among women are related to knowledge of RCA and personal lifestyle while male opinions concerning RCA bear no statistical relationship to personal lifestyle. These results imply the possibility that knowledge of RCA and opinions concerning RCA among women can be effectively promoted by health education. The results of our analyses concerning the three aspects of RCA and personal lifestyle also indicate that attitudes toward RCA are positively correlated with factors other than knowledge and opinions concerning RCA; this implies the possibility that health education has but a limited impact on attitudes toward RCA. PMID- 1749114 TI - [Regional distribution of sulfatide in human kidney, and anti-sulfatide antibodies in sera from patients with nephritis detected by TLC immunostaining]. AB - Glycolipids were isolated from lipid extract of human kidney. The major neutral glycolipids have been identified as ceramide monohexoside (CMH), ceramide dihexoside (CDH), ceramide trihexoside (CTH), and globoside. As the major acidic glycolipids, Gal Cer sulfate (sulfatide), Lac Cer sulfate, GM3, sialosyl paragloboside, GD3, and disialosyl paragloboside were identified and the most abundant component was sulfatide. Sulfatide was 2 times more concentrated in medulla compared to cortex. In addition, the localization of sulfatide antigen was determined in renal sections by immunoperoxidase staining method. Strong positive staining with sulfatide was observed in distal tubules, limbs of Henle's loop and collecting tubules of normal tissue, whereas glomeruli were negative of staining. However, positive results of glomerular epithelial cells occurred in FSGS and IgA nephropathy so far. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with nephritis contain antibodies to the sulfatides of human kidney as determined by the direct binding of antibody to thin-layer chromatograms. These results suggest that sulfatide antigen may play important role in the occurrence and aggravation of glomerular diseases. PMID- 1749115 TI - [Study on the assay of uremic protein-binding inhibitors: furan compound and hippuric acid]. AB - Plasma levels of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (FA) and hippuric acid (HA) were studied in healthy subjects, uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Analysis of FA and HA in the plasma were performed by gas chromatography with capillary column. The mean value of FA in HD patients (16.7 +/- 6.1 micrograms/ml) was significantly higher than these in healthy subjects (3.6 +/- 1.0 micrograms/ml) and in patients on CAPD (4.1 +/- 3.7 micrograms/ml) (p less than 0.01). HA levels in CAPD and HD groups were higher than those in healthy controls (2.4 +/- 0.8 micrograms/ml). In addition, the values in HD patients (46.7 +/- 53.5 micrograms/ml) were more increased than those in CAPD (18.5 +/- 16.5 micrograms/ml) (p less than 0.05). Approximately 95% of total FA and 25% of HA were bound to the plasma protein. However, the plasma level of HA was significantly reduced by HD therapy, whereas that of FA was not altered. In the previous study, it was described that no effect of HD on the percent of the binding of acid drugs to the plasma protein in the uremic plasma was observed. Therefore it is supposed that FA is more involved in the binding of drugs to the plasma protein in comparison with HA. The peritoneal losses of FA and HA in CAPD were 2.3 +/- 1.3 mg/day and 276 +/- 40 mg/day, respectively. As the duration of HD became longer, plasma concentrations of FA in HD patients were more increased. In general, they were maintained to be comparatively low in patients on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749116 TI - [The effect of abnormal lipid metabolism to glomerular injury]. AB - To clarify the effect of abnormal lipid metabolism and lipid deposition in glomerular injuries, we conducted clinical and pathological examination of various glomerulonephritis. There was no relationship between serum TC, TG or apo B and renal deposition of apo B or TG in glomerulonephritis. Apo B staining was intense for MCNS but was very weak for FGS. The staining was more intense in higher grade of glomerular injury in IgAN. Apo B demonstrated a specific pattern for MN, MPGN and lupus nephritis. These data suggest that apo B deposition reflects disturbance of glomerular permselectivity of macromolecules including abnormal influx, transport and endocytosis of macromolecules. PMID- 1749117 TI - [Intravenous cyclophosphamide therapy in patients with steroid-resistant lupus nephritis]. AB - We evaluated short term clinical effects of intravenous cyclophosphamide (iv CyP) therapy performed by every three month in 7 patients with steroid-resistant lupus nephritis. Significant improvements were observed in daily urinary protein excretion (3.1 to 0.83 g/day), creatinine clearance (65.4 to 95.3 ml/min), CH 50 levels (20.8 to 37.4 U/ml), and anti-DNA antibody titer (26.6 to 7.0 U/ml). In addition, the mean daily dose of prednisolone (PSL) could be markedly reduced from 38.6 mg to 13.9 mg at the final observation. Two patients suffered from Herpes Zoster infection at a few months after ivCyP therapy, however this incidence were not considered as critical side effect which reached to the discontinuation of this therapy. We concluded that ivCyP therapy by every three months were safety and achieved beneficial clinical effects on steroid-resistant lupus nephritis as far as short observation. On the contrary, the long term effect of this mode of therapy is to be defined. PMID- 1749118 TI - [The relationship between complement C3 receptors (CR1, CR3) on polymorphonuclear leukocytes and complement fragments during hemodialysis]. AB - The expression of complement receptor type 1 (CR1) and type 3 (CR3) on polymorphonuclear leukocytes (PMNs) and generation of complement fragments, C3a, C5a, C4d, iC3b and Bb, were studied in patients during hemodialysis using cuprammonium rayon (Cu) membranes. Furthermore, the relation between the expression of CR1 and CR3 on PMNs from healthy donors and complement fragments was investigated. The expression of CR1 and CR3 on PMNs increased during hemodialysis. Plasma C3a, C5a and iC3b levels increased in the first 15 minutes and then decreased at 120 minutes of dialysis. But plasma Bb level remained high until the end of hemodialysis. Purified Bb had no effect on the expression of CR1 and CR3 on PMNs, but C5a augmented those expression in vitro. Nafamostat mesilate, an artificial proteinase inhibitor, inhibited augmentation of complement receptors on PMNs in concentration dependent fashion. C5a generated through the activation of complement was thought to take an important role in the increased expression of CR1 and CR3 on PMNs. PMID- 1749119 TI - [Clinicopathological studies of renal disorders in patients with progressive systemic sclerosis]. AB - The renal impairments were studied clinicopathologically in 57 patients with progressive systemic sclerosis (scleroderma). Proteinuria, hematuria, azotemia and hypertension, used as markers for renal involvements, were observed in 3 (5.3%), 4 (7.0%), 2 (3.5%) and 6 patients (10.5%) respectively, at the initial examination. Hypertension was increased 2.6 times at the last observation, although the incidence of other three markers have not changed during the follow up period. Finally, 17 out of 57 patients (29.8) revealed more than one of these clinical markers throughout the study. The decrease of GFR (CThio) was noticed in 3 out of 36 cases (8.3%), however that of RPF (CPAH) in 11 of 36 patients (30.6%), including 5 without abnormal clinical markers. Histological studies were performed in 12 patients. One showed crescentic glomerulonephritis, two membranous nephropathy, and the remaining 9 minor glomerular abnormalities. On the other hand, the vascular changes such as intimal proliferation of interlobular arteries were frequently observed. The frequency of pulmonary involvements, skin ulcer and gastro-intestinal involvement in the patients with renal lesions were not significantly different from that of the non-renal group. The level of RPF was significantly lower in the patients with skin ulcer than that of those without skin ulcer. No significant difference was noticed in the frequency of renal involvements between the patients with or without anti-Scl-70 antibody. PMID- 1749120 TI - [A clinicopathological study of 17 cases recovered from acute tubular necrosis]. AB - Renal biopsy specimens of 17 cases recovered from clinical acute renal failure (ARF) and subsequent pathological acute tubular necrosis (ATN) were analyzed clinicopathologically. The cases were divided into two groups: 11 patients who underwent hemodialysis (HD group) and 6 patients who did not need hemodialysis (non-HD group). The varied histopathological findings were assessed by scoring as parameters and were compared between the two groups and with severity of the clinical conditions as well. Among the histopathological parameters, tubulorrhexis and cell infiltration, mainly composed of lymphocytes, in the interstitium as well as in the tubules were significantly marked in the HD group, while other parameters such as necrosis, flattening, vacuolization and regeneration of the tubular epithelial cells and presence of casts were not necessarily significant. Tubulorrhexis were supposed to reflect the severity of the attack factors on the kidney which had caused ARF and subsequent ATN, and to have caused in turn prolongation of the recovery of the impaired renal function. Cell infiltration, which was divided into 4 types according to the corresponding conditions, might probably have affected the prolonged recovery in the HD group. In 8 cases which could be followed up for 2 years, non showed aggravation of the renal function. PMID- 1749121 TI - [A case of sarcoid granulomatous interstitial nephritis improved by steroid therapy]. AB - We report a case of sarcoid granulomatous tubulointerstitial nephritis diagnosed by renal biopsy. A 60-year-old man presented with productive cough, and exertional dyspnea of 3 months duration. A chest X-ray film revealed diffuse reticulonodular infiltrates in both lung fields. A transbronchial lung biopsy specimen showed inflammation of the alveolar septum associated with non-caseating granulomas. The patient also had tubular proteinuria and glucosuria. Ga scintigraphy demonstrated an abnormal accumulation of gallium in both lungs and kidneys. Renal function tests revealed tubular dysfunction. Tubulointerstitial nephropathy was suspected. A renal biopsy specimen exhibited tubulointerstitial nephritis associated with numerous non-caseating granulomas, similar to the findings of the lung biopsy specimen. No glomerular abnormalities were evident. Later, a scalene node biopsy confirmed the diagnosis of sarcoidosis. Prednisolone therapy yielded a favorable outcome for both the renal and pulmonary involvement. During the corticosteroid therapy, measurement of the urinary beta-2 microglobulin concentration proved a valuable monitoring tool for assessing the recovery of the tubular impairment. PMID- 1749122 TI - Proceedings of the 68th annual meeting of the Physiological Society of Japan. March 27-29, 1991 (Kyoto). PMID- 1749123 TI - [Effects of repeated presentation of stimuli on the learning and recognition of a highly structured set of stimuli]. AB - In this article, we report the results of two experiments which investigated the repetition effect of stimulus presentation on recognition judgement. Each stimulus in sets of stimuli had five or six binary attributes. Any two stimuli could be mutually transformed by changing values of some attributes. In the experiments, subjects learned and immediately recalled stimuli, presented one after another. Learning was repeated several times. In the following recognition task, subjects were presented, one after another, the set of test stimuli consisted of old and new stimuli and judged whether each stimulus was old or new, and rated the degree of confidence of the judgement. The results showed that when learning of the presented stimuli progressed, the degree of the confidence of 'old' judgement increased for the presented stimuli, while for the new stimuli, it increased, at first, and then decline. PMID- 1749124 TI - [Determinants of requesting expressions: referring to a speaker's state]. AB - The purpose of this study is to examine situational determinants of one type of expressions used in situations of requests: expressions in which a speaker refers to his surroundings or his own condition without using conventional forms of requests (expressions of a speaker's state: ESSs). In four experiments subjects read scenarios in each of which the protagonist needed to make a request, and then the subjects made a note of how they would say in that situation. The findings were as follows: (Experiment 1) Subjects used ESSs more when it was obligatory for the addressee to obey the request than when it was not. (Experiment 2) Intimacy between the protagonist and the addressee did not uniformly influence subjects' use of ESSs. (Experiment 3) When the addressee made a previous statement which indicated his knowledge of the protagonist's goal, ESSs decreased. (Experiment 4) Subjects used indecisive ending expressions ( kedo,-ga) in ESSs more when the addressee's behavior brought benefits to the protagonist than when it did not. PMID- 1749125 TI - [Interaction between visual and auditory memories in repetitive learning]. AB - A serial recall experiment under same- and cross-modality conditions was carried out according to Hebb's (1961) paradigm. Subjects memorized strings of nine digits in 18 trials, which were divided into early trials and late ones. Under the same-modality condition the strings used in the 18 trials were presented through the same modality, i.e., visual or auditory, whereas under the cross modality condition the strings used in the early and late trials were presented through two different modalities. A repeated string and unrepeated strings were presented 3 and 6 times respectively in both early and late trials. The results showed that (1) repetitive learning in the same-modality occurred for both visual and auditory; (2) there was a non-additivity of cross-modal repetitive learning from auditory to visual, whereas there was an additivity of cross-modal repetitive learning from visual to auditory. We inferred that the visual inputs received both visual coding and auditory coding through an audio-transformation so as to be separately memorized in visual and auditory memories, whereas the auditory inputs were memorized in the auditory memory through the auditory coding alone. PMID- 1749126 TI - [Comparison of learning and concentration effects of "knowledge of results (KR)" in alpha-wave feedback training]. AB - Effects of KR on biofeedback have conventionally been limited by learning factor. The effects of feedback on an increase in EEG alpha have been believed to be so limited as well. However, the effects of KR are also believed to include factors such as motivation and concentration. In this study, the tendencies for alpha rhythm to change were analysed and compared under 3 different KR conditions in order to demonstrate the existence of the later factors. Effects of two parameters, alpha index and microvolt integral value, were also compared. The KR conditions consisted of three types with regard to an increase in alpha rhythm: true-KR, false-KR, and mixed-KR. Ten female college students underwent the feedback task for 10 minutes under each condition. It was shown that (1) the degree of achievement and temporal profile under three KR conditions demonstrated the involvement of learning factor as well as motivation and concentration factors, and (2) alpha index showed the effects of learning, motivation and concentration in KR more distinctly than the microvolt integral value. PMID- 1749127 TI - [The influence of between-channel selection on the brain potentials related to within-channel selection in auditory attention]. AB - Event-related potentials (ERPs) were recorded during a selective listening paradigm similar to a previous study (Okita, 1989). Stimuli were random sequences of five vowels and a tone pip in two "channels' (separated by location, left and right). The difficulty of between-channel selection was varied in discriminability of location, easy (EL) or hard (HL), whereas within-channel selection was manipulated by designating either tone (T), one vowel (1V), or two vowels (2V) as targets. Subjects were required to attend to one channel and detect targets therein. ERPs for the EL condition replicating the earlier study, confirmed the effects of within-channel selection on the early phase of attention related negativity (Nd): the early Nd being larger, the higher the target/nontarget selection load. In the HL condition, however, the 1V/2V difference disappeared: the early Nd effect was reduced for 2V, but prolonged in duration for 1V. The interaction between selection processes of the between- and within-channel was discussed in relation to the allocation of limited attentional capacity for operations rechecking outcomes of a preattentive target classification stage. PMID- 1749128 TI - [The effect of orthographic familiarity on recall of stimulus items read aloud]. AB - The purpose of this study was to examine the effect of orthographic familiarity on free recall of Katakana words which were read aloud. Two experiments were conducted to compare Katakana items with Hiragana ones about recall performance in incidental learning paradigm, in which subjects were instructed to perform a reading aloud task. In Experiment I, an immediate recall test was used. Number of correct free recall for high imagery items was larger than low imagery ones. In Experiment II, 30-s delay was inserted between an orienting task and a recall test. The recall performance indicated the superiority of Hiragana items. This result showed that the higher orthographic familiarity of stimulus item was, the poorer performance of its recall. It was interpreted in terms of the effect of cognitive effort on recall. PMID- 1749129 TI - Mandatory testing and disclosure of health care workers' HIV status offers patients little protection. PMID- 1749130 TI - The Pediatric Committee: our dream is finally a reality. PMID- 1749131 TI - The leading edge of nursing specialty certification renewal programs. PMID- 1749132 TI - ED physician staffing guidelines erroneously attributed to Joint Commission on Accreditation of Healthcare Organizations (JCAHO) PMID- 1749133 TI - Case report of adenosine used for a patient with paroxysmal supraventricular tachycardia. PMID- 1749134 TI - Trauma research assistant complains of male bashing. PMID- 1749135 TI - Guest editorial on nursing diagnosis applauded. PMID- 1749136 TI - More applause for guest editorial on nursing diagnosis. PMID- 1749137 TI - Telling the patient about a terminal diagnosis: is it the decision of the family or the ED staff? PMID- 1749138 TI - Similar packaging for heparin, potassium chloride, and 1% lidocaine by one drug manufacturer causes concern. PMID- 1749139 TI - A 6-month-old paraplegic infant with spinal cord injury without radiologic abnormalities (SCIWORA) PMID- 1749140 TI - I am an emergency nurse: twelve hours in the pediatric emergency department. PMID- 1749141 TI - Atraumatic rhabdomyolysis in a 20-year-old bodybuilder. PMID- 1749142 TI - Improperly positioned passenger-restraint systems as associated mechanisms of injury in motor vehicular collisions. PMID- 1749143 TI - A 3-year-old with spinal cord injury without radiographic abnormality (SCIWORA). AB - The results of hyperextension, flexion, and traction injuries can be devastating and permanent; the results of treatment, dismal. Reducing the incidence of spinal cord injury requires education about the proper use of automobile restraint devices, scene of injury immobilization, selection of child-appropriate furniture, diving safety, and increased awareness of the risks of contact sports. Immediate treatment should center on strict cervical spine immobilization until complete neurologic and radiologic evaluations have been completed, with special awareness of the possibility of SCIWORA. PMID- 1749144 TI - Near-hanging injury: two case studies and an overview. AB - Near-hanging injuries result in respiratory, cardiac, neurologic, metabolic, and psychiatric problems. A patient surviving an attempted hanging can arrive at the emergency department in a comatose state, as documented in case 1, or in a conscious but disoriented state, as in case 2. Severe neurologic deficits are often reversible in cases of near-hanging. Regardless of initial findings, aggressive treatment of near-hanging victims should be initiated. PMID- 1749145 TI - The American Red Cross: a nursing-oriented overview of services. AB - Nurses are at the heart of many Red Cross services. Their expertise is recognized and often sought throughout the organization. Nurses can, through active participation and personal donation, assist the agency in reaching its humanitarian goals. The resources, services, and assistance available through the Red Cross give the busy emergency nurses more options in meeting the needs of patients. Nurses in turn can be a resource for the Red Cross. The strength, support, and commitment of dedicated volunteers give meaning to the endeavors of the American Red Cross. PMID- 1749146 TI - A hospital-wide approach to crisis control: one inner-city hospital's experience. PMID- 1749147 TI - A survey of emergency department triage in 185 hospitals: physical facilities, fast-track systems, patient-classification systems, waiting times, and qualification, training, and skills of triage personnel. PMID- 1749148 TI - Mnemonics for cardiac care. PMID- 1749149 TI - Law and the emergency nurse--pre-COBRA days. PMID- 1749150 TI - Acquired immunodeficiency syndrome: ten years later. PMID- 1749151 TI - Patient teaching in the emergency department: vaginal bleeding during early pregnancy. PMID- 1749152 TI - Immobilizing children in care safety seats--why, when, and how. PMID- 1749153 TI - Visual acuity testing. PMID- 1749154 TI - Pulse oximetry: pearls and pitfalls. PMID- 1749155 TI - A 19-year-old woman, four months' pregnant and with a history of headache. PMID- 1749156 TI - What we do. PMID- 1749157 TI - [Treatment of dysplasia of the gastric mucosal epithelium]. AB - Examined were 53 patients with dysplasia of the gastric mucosal epithelium revealed at endoscopic and histologic study. In detection of moderately pronounced dysplasia, the conservative treatment of the underlying disease with endoscopic and histologic control every 6 mos is indicated; in severe dysplasia- conservative treatment with dynamic control every 3 mos; in absence of positive dynamics of the dysplastic process within a year, or in suspected malignant transformation--the operative intervention, the volume of which is determined by spreading of the foci of dysplasia. The patients operated on for severe dysplasia of the gastric mucosal epithelium should be under continuous supervision. PMID- 1749158 TI - [Changes in immunologic reactivity in patients with gastrointestinal bleeding]. AB - The disorders in immunologic reactivity in acute gastrointestinal bleeding were studied in dynamics in 160 patients. Pronouncement of disorders in the T-system of immunity, activation of the reactions of specific sensibilization and autoallergic phenomena depend on severity of the blood loss. In ulcer location in the duodenum, the performance of an organ-preserving operation with vagotomy and elimination of the ulcer which is a source of antigen stimulation is preferable. PMID- 1749159 TI - [Blood flow in the gastric mucosa and components of the kallikrein- kinin system in patients with duodenal ulcer]. AB - The results of study of the blood flow rate in the gastric mucosa by means of intraoperative rheography and content of the main components of kallikrein-kinin system in the systemic and regional blood flow were compared. It was established that increase in the volumetric blood flow rate in patients with a complicated duodenal ulcer disease was caused by activation of the kallikrein-kinin system in the regional blood flow. Blockade of the celiac plexus has a pronounced effect on the state of a kallikrein-kinin system. PMID- 1749160 TI - [Effect of suture material on the development of anastomosis reaction after gastric resection]. AB - In the experiment on rabbits, response of tissues of the stomach and small intestine to implantation into in of the catgut, capron, capromed "DC" threads and an absorbable Dexon thread was studied. Catgut, when absorbing in the tissues, causes acute purulent-necrotic response, edema of the tissues, their hyperplasia with development of a deep scar. The optimal suture material in gastric resection is the absorbable thread--polymer of polyglycolic acid Dexon, which causes minimal reaction after its implantation into the wall of a stomach. Catgut replacement by the synthetic absorbable threads, first of all by Dexon, is one of the important factors in prophylaxis of anastomositis after gastric resection. PMID- 1749161 TI - [Pylorus-reconstructing operations in complicated gastric and duodenal ulcer]. AB - The results of treatment of 185 patients with complicated gastric and duodenal ulcer disease have been analysed. The results of operative treatment in 132 patients followed up for the period of from 1 to 7 years were studied. In gastric ulcer, resection of the stomach with preservation of the pyloric sphincter, or its reconstruction by means of the flaps taken from the antrum, is indicated; in duodenal ulcer--vagotomy, ulcer excision added by pylorus-preserving and pylorus reconstructing methods of drainage operations. PMID- 1749162 TI - [Experimental basis for the prophylactic use of litonit in acute gastroduodenal erosion and ulcer]. AB - The certain indices of morphofunctional state of the cellular membranes and mass of the stress-competent organs of rats in acute stress and its prophylaxis by means of lithonit--a new native atypical tranquilizer with a neotropic action were studied. The immobilization-cold stress caused a statistically significant adrenal hypertrophy and deep degradation of the thymico-lymphatic system. Prophylactic administration of lithonit for 7 days had a protective action on the organs studied. In prophylactic administration of lithonit, the accumulation of membranotoxic products of peroxide oxydation of lipids reduced considerably. PMID- 1749163 TI - [Surgery in bleeding stenosing pyloroduodenal ulcer]. AB - The results of surgical treatment of 147 patients with a bleeding stenosing pyloroduodenal ulcer are presented. The operation of choice in this pathology is a selective proximal vagotomy in combination with the original methods of ulcer excision and drainage operations, and as well a selective proximal vagotomy with antrectomy. Gastric resection is indicated in patients with decompensated stenosis of gastric outlet and pronounced disorders in motor-evacuatory function of the stomach. In patients with a severe, or extremely severe state, the ulcer excision in combination with pyloroduodenoplasty dilating the lumen is expedient. PMID- 1749164 TI - [Radical treatment of penetrating duodenal ulcer]. AB - The results of treatment of 450 patients with duodenal ulcer have been analysed. Of them, in 198 (44%), ulcer penetration into the adjacent organs was revealed. An excellent and good results were noted in 80.3% of the patients. Vagotomy with an ulcer excision and subsequent restoration of the pyloric sphincter function in penetrating duodenal ulcer permits to reduce lethality and achieve stable recovery of the majority of patients. PMID- 1749165 TI - [Surgical treatment of patients with a bleeding giant ulcer of the stomach and duodenum]. AB - The results of surgical treatment of 112 patients with a bleeding giant gastric, or duodenal ulcer, comprising 18.6% of the number of patients with acute ulcerous gastrointestinal bleeding operated on in the emergency order are presented. The use of active surgical tactics permitted to increase the specific weight of radical operations to 62.8%, reduce the incidence of early postoperative complications 1.8-fold, lethality--3.4-fold when compared with the results of the use of active-expectant tactics. An operation of choice in bleeding giant gastric ulcer is Billroth-I resection of the organ, or its suprapyloric resection; in ulcer location at the pyloroduodenal region--selective proximal vagotomy with ulcer excision, or selective vagotomy with antrectomy. To arrest bleeding in performance of minimal, or organ-preserving operation with vagotomy, it is necessary to perform ulcer excision, because after closing the bleeding ulcer, or suturing the bleeding vessel in an ulcer, 25.8% of the patients developed recurrency of the bleeding at the nearest postoperative period. PMID- 1749166 TI - [Combined seromuscular vagotomy in the treatment of pyloroduodenal ulcer]. AB - The posterior truncal and anterior proximal seromyotomy were performed in 150 patients. One and three years after the operation, 102 of the patients were examined. An excellent and good results were noted in 86.3%, a satisfactory one- in 13.7% of the patients. No unsatisfactory result was noted. The given modification has the following advantages: rapid elimination of the pain syndrome, low traumaticity, technical simplicity and short duration of the operation. PMID- 1749167 TI - [Some problems of the surgical treatment of stomach and duodenal ulcer]. AB - The analysis of the results of surgical treatment of the gastric and duodenal ulcer disease in 191 patient under conditions of surgical department of the central district hospital was carried out. It was established that performance of the organ-preserving operation with vagotomy in duodenal ulcer disease permitted to reduce the mean duration of postoperative treatment and temporary invalidity, reduce the lethality. In gastric ulcer, the best result was obtained when using Billroth-I and stepped resection of the stomach. PMID- 1749168 TI - [Simultaneous operations in gastric and duodenal ulcer]. AB - The experience with surgical treatment of 112 patients with gastric and duodenal ulcer disease associated with pathology of the abdominal organs is summarized. Most frequently in ulcer disease, sliding hiatal hernia (34.1% of cases) and adhesive disease (25.7%) were revealed. In all the patients, the simultaneous operations were performed. The incidence of postoperative complications was 13% and didn't exceed that in the control group of patients, who underwent only the operations on the stomach and duodenum. PMID- 1749169 TI - [Surgical treatment of multiple and associated gastroduodenal ulcers]. AB - Operated on were 53 patients with multiple and associated gastric and duodenal ulcers, which were characterized by a high rate of complications (54.7%) and low effectiveness of the conservative treatment. Gastric resection with removal of the pathologically changed areas was the main operation. After the operation, 2 (3.7%) patients died. PMID- 1749170 TI - [Patient's reaction to surgical trauma in surgical treatment of duodenal ulcer]. AB - Evaluation of metabolism and state of central hemodynamics in 134 patients with duodenal ulcer before the operation and at the early postoperative period was carried out. It was established that pronouncement of postaggressive response of an organism to trauma in surgical treatment of a duodenal ulcer didn't depend on a type of the operation due to use of the modern methods of anesthesia. Therefore, moderate pronouncement of such a response after the organ-preserving operations can't be a criterium for the wide use of surgical treatment of an uncomplicated duodenal ulcer. PMID- 1749171 TI - [Prophylaxis of intestinal paresis after colon surgery]. AB - In the clinic, a method for prophylaxis of postoperative intestinal paresis with the use of local consecutive electroimpulse influencing upon the zones- pacemakers of the small and large intestine by a current with a frequency corresponding to the physiologic frequency of contractions of a given intestinal segment at the time corresponding to the physiologic one in restoration of motor activity of the intestine have been developed. Electric stimulation of a pacemaker contributes to organization and synchronization of activity of the neural ganglia and amplification of their myoelectrical signal. As a result, the activity of proximal pacemakers predominates over that of the distal ones and contributes to restoration of a gradient of propulsive activity. The method was employed in 53 patients. The time of restoration of peristaltic and propulsive functions of the intestine corresponded to the physiologically substantiated time. PMID- 1749172 TI - [Methods of surgical treatment of ulcerative gastrointestinal bleeding]. PMID- 1749173 TI - [Intragastric pH-metry in the surgical treatment of ulcers]. PMID- 1749174 TI - [Pathogenesis, prophylaxis and therapy of Roux syndrome]. PMID- 1749175 TI - [Urologic complications of non-specific colitis]. PMID- 1749176 TI - [Errors and complications of pylorus-preserving gastric resection]. PMID- 1749177 TI - [Acute gastric dilatation complicated by spontaneous rupture]. PMID- 1749178 TI - [Perforation at gastroscopy of a gastric ulcer penetrating into the liver]. PMID- 1749179 TI - [Method for determination of the completeness of vagotomy]. PMID- 1749180 TI - [Electrostimulation of gastric peristalsis as a method of prevention of postvagotomy gastroplegia in the early postoperative period]. PMID- 1749181 TI - [Modification of Billroth-1 gastric resection in penetrating pyloroduodenal ulcer]. PMID- 1749182 TI - [A method of gastric stump suture technique]. PMID- 1749183 TI - [Method of esophagofundophrenoplication in the surgery of gastric and duodenal ulcer]. PMID- 1749184 TI - [Jejunoplasty in surgical treatment of chronic and malignant gastric ulcers]. PMID- 1749185 TI - [Fibrosarcoma of the small intestine as a cause of repeated profuse intestinal bleeding]. PMID- 1749186 TI - [Reconstructive surgery after subtotal resection of the small intestine and placing the intestinal anastomosis]. PMID- 1749187 TI - [Small intestinal ulcer complicated by perforation and hemorrhage]. PMID- 1749188 TI - [Small intestine ulcer complicated by bleeding and perforation]. PMID- 1749189 TI - [Bleeding neurinoma of the duodenum]. PMID- 1749190 TI - [Evaluation of the acid producing function of the stomach by pH-metry in surgical treatment of duodenal ulcer]. AB - The comparative analysis of changes in acid production according to the data of pH-metry in 266 patients with duodenal ulcer disease after surgical treatment was carried out. The peculiar features of the dynamics of gastric acid production and dependance of the incidence of ulcer recurrences on a volume of the intervention performed have been established. PMID- 1749191 TI - [Severe complications of ulcer in an elderly patient]. PMID- 1749192 TI - [Omental coccidioidosis as a cause of gastrostasis in a patient after vagotomy]. PMID- 1749193 TI - [Treatment of acute Roux syndrome after vagotomy and gastric resection]. PMID- 1749194 TI - [Postural symptom in perforative ulcer of the stomach and duodenum]. PMID- 1749195 TI - [Repeated development of trichobezoar in the stomach]. PMID- 1749196 TI - [Foreign body of the pleural cavity after gastric resection]. PMID- 1749197 TI - [Asymptomatic presence of multiple metallic foreign bodies in the stomach]. PMID- 1749198 TI - [Recovery of a child operated on for necrosis of the abnormally situated stomach]. PMID- 1749199 TI - [Effectiveness of the parenteral and enteral feeding in the comprehensive treatment of the postoperative fistulas of the alimentary canal]. PMID- 1749200 TI - Differences in the risk factor patterns for coronary heart disease in China, Japan, and Germany. AB - In Asia coronary heart disease mortality is almost 10 fold less frequent than in European countries. These findings attract interest to search for different risk factor patterns. From 1982 to 1985 epidemiologic surveys were carried out in China (n = 2047), Japan (n = 7580) and Germany (n = 6052). Healthy, male subjects, aged 30 to 59 years were enrolled. The prevalence rate of hypertension for the Germans was 20% versus 18% for the Japanese, and 11% for the Chinese. About 69% of Chinese, 55% of Japanese, and 37% of Germans were smokers. About 66% of the Germans were overweight (BMI greater than 25), 17% of the Japanese, and 11% of the Chinese. The highest risk group with cholesterol levels of greater than 300 mg/dl included no Chinese subject, 0.1% of the Japanese, but 5% of the Germans. The lipoprotein profiles among the Japanese and the Chinese collectives typically showed antiatherosclerotic characteristics, whereas most Germans exhibited profiles which support development of atherosclerosis. About 36% of the participants from Germany showed 3 or more risk factors accumulated per person (Japan and China 5%). Multifactorial risk factor reduction for Germany is recommended. PMID- 1749201 TI - The spontaneous course of small abdominal aortic aneurysms. Aneurysmal growth rates and life expectancy. AB - Since abdominal ultrasonography has become a routine diagnostic procedure, increasing numbers of small asymptomatic abdominal aortic aneurysms are detected incidentally. Of 128 patients (108 male, 20 female) with abdominal aortic aneurysms, 96 patients were observed clinically and by repeated ultrasound studies for an average of 3.47 years, adding up to a total observation period of 333 patient-years. Among these 96 patients, 72 had small aneurysms (averaged diameters less than 5 cm). Three of them were lost to follow up. None of the remaining 69 patients died from rupture, 20 died from other causes and 8 patients were successfully operated. Of the patients with a large aneurysm one was lost to follow up. Five patients of the remaining 23 died as a result of rupture, 7 were successfully operated. The average growth rate of small aneurysms was 0.18 cm/year, whereas the larger aneurysms showed a growth rate of 0.28 cm/year (diameter). The survival rate of patients with small aneurysms was 94% after one year, 80% after 3 years, and 73% after 5 years, indicating that life expectancy is reduced in patients with an aneurysm of the abdominal aorta, but not because of complications of the aneurysm. PMID- 1749202 TI - Zinc levels after intravenous administration of zinc sulphate in insulin dependent diabetes mellitus patients. AB - Diabetic patients commonly have increased urinary excretion of zinc, although blood concentrations may be normal, lowered, or raised. We analyzed zinc levels in plasma and urine after an intravenous overload of zinc sulphate (8 mg) in 22 patients with insulin-dependent diabetes mellitus (IDDM) and 22 healthy individuals. No significant differences were found in basal levels of serum zinc in either group (111 +/- 29 micrograms/dl in IDDM vs 119 +/- 19 micrograms/dl in controls), although urinary excretion of zinc was significantly raised in diabetics (1396 +/- 622 micrograms/24 h) versus controls (611 +/- 235 micrograms/24 h). After zinc overload, both serum and urinary levels of this element varied between the two groups. Serum zinc in IDDM patients initially increased more markedly, and subsequently showed a more significant decline, than in controls. Urinary zinc levels in IDDM patients, in contrast to control values, showed no increase after overload. These alterations in serum and urinary zinc concentrations suggest that our diabetic patients may be zinc-deficient. PMID- 1749203 TI - Effects of atenolol, slow-release nifedipine, and their combination on respiratory gas exchange and exercise tolerance in stable effort angina. AB - The effects of atenolol, nifedipine, and their combination on gas exchange and exercise tolerance were studied in 27 patients with effort angina and normal global ventricular function in an open-label and randomized cross-over trial. Symptom-limited semi-supine exercise tests using a ramp protocol (20 W/min) with simultaneous breath-by-breath analysis of gas exchange were carried out after a 4 day wash-out period and after consecutive 2-week treatment periods with atenolol (50 mg b.i.d.), slow-release nifedipine (20 mg b.i.d.), and their combination (b.i.d.). Exercise tolerance was not significantly higher with atenolol than with nifedipine [118(24) vs 113(23) W]. Combination therapy [120(23) W] was more effective than monotherapy with nifedipine (p less than 0.05) but produced no further increase in exercise tolerance over atenolol monotherapy. Maximum oxygen uptake was not significantly different among the treatments. In the range of light to moderate exercise, the slope of the VO2-workload regression line expressed as ml.min-1.W-1 was lower with atenolol than with nifedipine [8.64(1.59) vs 10.28(1.74), p less than 0.005] and intermediate with combination therapy [9.99(1.83)]. The intercept on the VO2 axis was higher with atenolol than with nifedipine [366(111) vs 299(113) ml.min-1, p less than 0.05]. A similar pattern of results was seen when the drug effects on the slope of the VCO2 workload relation were analyzed. VE was higher with nifedipine than with atenolol at all points of the regression analysis [greater than 30 W].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749204 TI - Thromboxane production and platelet aggregation in type 2 diabetes mellitus without vascular complications. AB - Diabetic individuals frequently have platelet hyperaggregability and increased thromboxane (TXB2) production. To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids might alter thromboxane (TXB2) formation and platelet function, we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control (HbA1, fell from 12.0 +/- 0.3 to 9.0 +/- 0.3%; p less than 0.01) was associated with significant decrease in total cholesterol, triglycerides, and ratios of total cholesterol/HDL-cholesterol and LDL cholesterol/HDL-cholesterol. Palmitic acid of phospholipids decreased significantly, whereas eicosapentaenoic acid increased. Regardless of this, the ADP-induced platelet aggregability and sensitivity were not altered. There was no effect whatever on the TXB2 synthesis capacity of clotting whole blood (204.9 +/- 25.0 vs 222.8 +/- 32.0 ng/ml) over 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor were there any correlations to serum lipids and their fatty acid composition. Thus, we are tempted to speculate that glucose metabolism in diabetes itself does not affect platelet aggregation or TXB2 formation in type 2 diabetes mellitus. PMID- 1749205 TI - Sequence analysis of the cystic fibrosis gene in patients with disseminated bronchiectatic lung disease. Application in the identification of a cystic fibrosis patient with atypical clinical course. AB - The diagnosis of classical cystic fibrosis (CF) is easily made by clinical assessment alone, but may be missed or delayed in cases with an atypical clinical course. In a recent major study the age at diagnosis varied between 2 months and 47 years. For diagnostic purposes we have investigated the cystic fibrosis transmembrane regulator (CFTR) gene in 10 adult patients (age 18 to 45 years) with chronic obstructive pulmonary disease since childhood or adolescence and bronchiectases disseminated through both lungs. Only one subject (a 29-year-old male) had exocrine pancreatic insufficiency (PI); all others were pancreatic sufficient (PS). The first nucleotide (ATP)-binding fold of the CFTR was analyzed by direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA in these cases. Two patients with different phenotypes (one PI, one PS) were found to be homozygous for the common delta F508 mutation of the CFTR gene, which proved the diagnosis of cystic fibrosis in their cases and allowed genetic counselling. The PS patient had normal sweat tests and had not previously been recognized as having CF. Four other patients were heterozygous for delta F508, with no other mutation in exons 10 or 11 of the gene, and four patients had normal sequences of these exons. Because only about 70% of all CF chromosomes carry delta F508, the unexpectedly high frequency (4/8 = 50%) of heterozygosity for delta F508 among the non-delta F508/delta F508 patients with bronchiectases suggests that some of these might also have unrecognized CF with rare genotypes and mutations in any of the 22 exons not sequenced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749206 TI - Hyperparathyroidism after kidney transplantation: a retrospective case controlled study. AB - We studied retrospectively patients with hyperparathyroidism after successful renal allotransplantation. Since 1972, 1119 transplantations have been performed in our department, and 534 patients survive with functioning grafts. Hyperparathyroidism requiring parathyroidectomy developed in 32 (5.9%). The frequency of interventions increased markedly after introduction of cyclosporine A treatment in our unit. The time between transplantation and parathyroidectomy was 22.5 months (SD 16.5, range 1-82 months). The age of the patients was 49.0 years (SD 10.5, range 17-63 years); the group consisted of 16 female and 16 male patients. All patients but two (no measurement performed) repeatedly exhibited high serum parathormone and calcium levels and therefore underwent surgery. In comparison to a control group, matched for time of transplantation, age, sex, and cause of renal failure, the patients with hyperparathyroidism had longer dialysis treatment (54.2 months, range 9-132 vs 26.9 months, range 1-72) and exhibited lower phosphate concentrations in the early posttransplantation period. Before surgery, serum chemistry was different for hyperparathyroid and control subjects: serum calcium 2.80 +/- 0.23 mmol/l vs 2.48 +/- 0.13 mmol/l and alkaline phosphatase 157.4 +/- 92.0 U/l vs 85.2 +/- 51.5, respectively. We did not see any influence of oral phosphate binders, calcium supplementation, or vitamin D treatment on the development of parathyroid gland hyperactivity during dialysis treatment. Serum creatinine concentration did not change after parathyroidectomy. In four patients, long-term calcium supplementation after surgery was necessary. PMID- 1749207 TI - Primary malignant pericardial mesothelioma. AB - Malignant primary tumors of the pericardium are rare. The authors present two male patients, aged 44 and 67 years, not exposed to asbestos, who died from pericardial mesothelioma. Repeated evacuation of fluid from the pericardium due to cardiac tamponade failed to reveal the cause of pericarditis. In one case, the diagnosis was made on surgical exploration, and in the other, at autopsy. A significant difference between benign and malignant pericardial effusion was observed. In cases of pericardial mesothelioma, symptoms of epicardial involvement cannot be attributed solely to the hindered inflow and cardiac tamponade, but also to congestive heart failure due to myocardial infiltration. In one patient, temporary improvement was achieved, first by pronisone therapy and then by radiotherapy. PMID- 1749208 TI - The liver and inherited metabolic disorders. The 28th Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM). Birmingham, 1990. PMID- 1749209 TI - The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. AB - The mechanisms by which the liver maintains a constant supply of oxidizable substrates, which provide energy to the body as a whole, are reviewed. During feeding, the liver builds up energy stores in the form of glycogen and triglyceride, the latter being exported to adipose tissue. During fasting, it releases glucose and ketone bodies. Glucose is formed by degradation of glycogen and by gluconeogenesis from gluconeogenic amino acids provided by muscle. Ketone bodies are produced from fatty acids, released by adipose tissue, and from ketogenic amino acids. The major signals which control the transition between the fed and the fasted state are glucose, insulin and glucagon. These influence directly or indirectly the enzymes which regulate liver carbohydrate and fatty acid metabolism and thereby orient metabolic fluxes towards either energy storage or substrate release. In the fed state, the liver utilizes the energy generated by glucose oxidation to synthesize triglycerides. In the fasted state it utilizes that produced by beta-oxidation of fatty acids to synthesize glucose. The mechanisms whereby a number of inborn errors of glycogen metabolism, of gluconeogenesis and of ketogenesis cause hypoglycaemia are also briefly overviewed. PMID- 1749210 TI - Detoxification pathways in the liver. AB - The liver plays an important role in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is their ability to catalyse the oxidation, reduction and hydrolysis (Phase I) and/or conjugation (Phase II) of functional groups on drug and chemical molecules. The broad substrate specificity, isoenzyme multiplicity and inducibility of many of these enzyme systems make them particularly well adapted to handling the vast array of different chemical structures in the environment to which we are exposed daily. However, some chemicals may also be converted to more toxic metabolites by certain of these enzymes, implying that variations in the latter may be important predisposing factors for toxicity. Pharmacogenetic defects of xenobiotic biotransformation enzymes, a subclass of inborn errors of metabolism which are manifested only upon drug challenge, introduce marked variation into human populations for the pharmacokinetics and pharmacodynamics of therapeutic and toxic agents, and thus may have important clinical consequences for drug efficacy and toxicity. PMID- 1749211 TI - Hereditary variation of liver enzymes involved with detoxification and neurodegenerative disease. AB - Enzymes involved with the metabolic transformation of xenobiotics have recently been studied in patients with the neurodegenerative diseases, Alzheimer's disease, Parkinson's disease and motor neurone disease. Defects were detected in sulphur pathways and also, in the case of Parkinson's disease, in monoamine oxidase B. The possibility exists that the ability to cope safely with endogenous and exogenous substances which have neurotoxic properties is important in the pathogenesis of these diseases. Potentially such individuals could be identified preclinically and these diseases postponed by reduction in the load of toxin or modification of the relevant enzymic activity. PMID- 1749212 TI - Interrelationships of liver and brain with special reference to Reye syndrome. AB - Reye syndrome is an acute non-inflammatory encephalopathy that can be precipitated by toxic, infective, metabolic or hypoxic upsets. The biochemical changes point to mitochondrial dysfunction and this is substantiated by structural changes in mitochondria on electron microscopy. The toxic metabolites that accumulate are similar to those incriminated in hepatic encephalopathy and other metabolic diseases. These metabolites exert their deleterious effects by direct neuronal damage, neurotransmitter blockade, vascular damage, cerebral oedema, hypoxic ischaemic damage, demyelination, retardation of brain growth and neuronal storage. Brain capillary endothelial cells are very rich in mitochondria and mitochondrial disorders can effect the central nervous system primarily, and not just as a consequence of systemic metabolic upset. PMID- 1749213 TI - Fetal and neonatal bile acid synthesis and metabolism--clinical implications. AB - It has become apparent that with sophisticated technology we are now able to recognize defective bile acid metabolism in a wide variety of disease states. Recognition of specific aberrations, such as inborn errors in bile acid metabolism manifesting as neonatal cholestasis, offers new opportunities for therapeutic intervention. Future studies should determine the incidence of inborn errors in patients with enigmatic and unexplained liver diseases such as idiopathic neonatal hepatitis. PMID- 1749214 TI - Inborn errors of bile acid metabolism. AB - Cholesterol is converted to cholic acid and chenodeoxycholic acid by a series of reactions involving modifications to the steroid nucleus and oxidation of the side chain. These reactions can be affected by a number of inborn errors of metabolism. When this happens unusual bile acids or bile alcohols are synthesized; these can be identified using gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry techniques. Two defects affecting the modifications to the steroid nucleus have been described; both present with cholestatic liver disease of neonatal onset. The better characterized of the two- 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency--leads to excretion of 3 beta-7 alpha-dihydroxy-5-cholenoic acid and 3 beta,7 alpha,12 alpha trihydroxy-5-cholenoic acid in the urine. The liver disease improves dramatically on treatment with chenodeoxycholic acid. Deficient activity of 3-oxo-delta 4 steroid 5 beta-reductase is thought to be the cause of familial liver disease in some infants who excrete 7 alpha-hydroxy-3-oxo-4-cholenoic acid and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid in the urine. However, diagnosis of this disorder is problematical; a similar pattern of metabolite excretion can occur as a result of liver damage caused by viruses or inborn errors of pathways unrelated to bile acid synthesis. Defective side chain oxidation in patients with cerebrotendinous xanthomatosis (CTX) leads to synthesis of bile alcohols such as 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol. Patients with CTX do not have cholestatic liver disease. Their major problems (neurological disease, atherosclerosis and xanthomata) are caused by accumulation of cholestanol and cholesterol in the tissues. Bile acid precursors are probably diverted into synthesis of cholestanol. Chenodeoxycholic acid suppresses the production of abnormal metabolites from cholesterol (by inhibition of cholesterol 7 alpha-hydroxylase) and leads to improvement in the neurological disease. Defective side chain oxidation also occurs in peroxisomal disorders but this time it leads to accumulation of C27 bile acids such as 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta cholestanoic acid (trihydroxycoprostanic acid, THCA). This compound is readily detected in the bile and plasma of patients with defects of peroxisome biogenesis. In patients with defects of a single peroxisomal beta-oxidation enzyme (the 3-hydroxyacyl-CoA component of the bifunctional protein or the thiolase), the major C27 bile acid in bile may be 3 alpha,7 alpha,12 alpha,24 tetrahydroxy-5 beta-cholestanoic acid (varanic acid).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1749215 TI - Alpha 1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment. AB - The alpha 1-antitrypsin deficient subject (protease inhibitor (PI) phenotype ZZ) has an increased susceptibility to liver disease. The condition is most commonly identified in early infancy as a conjugated hyperbilirubinaemia with hepatitis (11%) or a bleeding state due to vitamin K malabsorption (2%). 50% of cases have cirrhosis and 25% die in the first decade of life. A further 2% present with cirrhosis in later childhood. Adult males are at risk of hepatoma development with or without cirrhosis. Diagnosis is by isoelectric focussing or allele specific oligonucleotide hybridization. The treatment is that of cholestasis and cirrhosis including transplantation. The pathobiology of the deficiency state, the mechanism of liver damage and the vulnerability of the newborn liver are discussed in this review. A plea is made for a trial of infusions of alpha 1 antitrypsin in early infancy, as is used safely but without proven efficacy in the emphysematous PIZZ subject. Prospects of therapy by gene modification are also reviewed. PMID- 1749216 TI - Alpha 1-antitrypsin deficiency and liver disease. AB - Alpha 1-antitrypsin (alpha 1AT) deficiency, one of the most common lethal hereditary disorders among Caucasians, is associated with emphysema in adults, while in children it is associated with liver disease. Produced in the liver and released into the plasma, alpha 1AT serves as the body's major inhibitor of neutrophil elastase, a powerful proteolytic enzyme capable of degrading extracellular structural proteins. The pathogenesis of the liver disease associated with alpha 1AT deficiency is not as well understood, but is clearly linked to specific mutations in coding exons of the alpha 1AT gene, and the resulting accumulation of alpha 1AT within hepatocytes. At present, therapy for the liver disease associated with alpha 1AT deficiency is symptomatic, with liver transplantation as a last resort. New strategies are being developed to suppress the accumulation of alpha 1AT by transferring the normal gene into the liver. PMID- 1749217 TI - Clinical presentation of metabolic liver disease. AB - Some clinical clues should alert paediatricians to the possibility of metabolic liver diseases. They can be classified into three categories: (i) Manifestations due to hepatocellular necrosis, acute or subacute, which can reveal galactosaemia, hereditary fructose intolerance, tyrosinaemia type I, Wilson disease and alpha 1-antitrypsin deficiency. Symptoms and signs suggestive of Reye syndrome should lead to a study of fatty acid oxidation and urea cycle enzymes. All these manifestations may necessitate a rapid diagnosis and treatment when liver dysfunction is severe. (ii) Cholestatic jaundice can reveal alpha 1 antitrypsin deficiency, Byler's disease, cystic fibrosis, Niemann-Pick disease and some disorders of peroxisome biogenesis. (iii) Hepatomegaly can reveal disorders with liver damage but also storage diseases such as glycogen storage diseases, cholesteryl ester storage disease and, when associated with splenomegaly, lysosomal storage diseases. Appropriate investigations for recognizing all these entities are proposed. PMID- 1749218 TI - Investigation of paediatric liver disease. AB - The investigation of children with liver disease falls into two categories: the investigation of the cholestatic baby and the investigation of the older child (over 2 years) with hepatomegaly. The approach to investigation is directed by the clinical features and employs many different investigational methods including biochemistry, haematology, radiology, electrophysiology and histology. As the clinical presentation of many diseases is similar, it is appropriate to perform a variety of first-line tests, proceeding to more complex investigations only as indicated. PMID- 1749219 TI - The role of histochemical investigations in metabolic disorders affecting the liver. AB - The application of histochemical techniques to the study of metabolic disorders affecting the liver can yield considerable information, provided the methods used are sound and the interpretation is not over-enthusiastic. The appropriate methods can give insight into liver function and can identify and localize a wide variety of carbohydrates, lipids, proteins and enzyme activities. It is often thought that tissue taken for histochemical analysis cannot be used for morphology, but properly prepared tissue will provide the architectural and cytological detail necessary for histological assessment. There are several advantages to the histochemical approach, the main ones being economy of use of the valuable tissue sample (in theory about 100 sections and tests can be done on a 1 mm depth of tissue) and that the results of the tests can be assessed in relation to the structure of the liver. There are two areas in which histochemical investigations are used: firstly, to detect cellular constituents, structures and cells not otherwise visible by routine methods. In this mode, histochemistry is an extension of the histological approach and constitutes a 'super haematoxylin and eosin' stain. Secondly, it is possible to assess enzyme activities and their localization, and in some well-defined instances to offer reliable indications of whether there is deficient activity, normal activity or enhanced activity. Although there is a body of opinion which believes that quantitative enzyme histochemistry is possible and reliable, the author has not found the data, in particular or lysosomal enzymes, to be reliable and remains unconvinced that this technique has a place in the study of pathological tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749220 TI - Techniques for studying hepatic metabolism in vivo. AB - Techniques for studying metabolic events in vivo in patients with inborn errors are reviewed. Loading or provocation tests that have been used widely are insensitive and frequently non-specific. Compounds labelled with stable isotopes can be used to study enzyme kinetics and substrate turnover, providing more detailed and specific information. Intracellular events may be studied using nuclear magnetic resonance spectroscopy. The results using these techniques to study patients with selected inborn errors are discussed, namely phenylketonuria, glycogen storage disease type I and propionic acidaemia. PMID- 1749221 TI - Tyrosinaemia type I--an update. AB - Tyrosinaemia type I is a recessively inherited disorder caused by a deficiency of fumarylacetoacetase (FAH), the last enzyme in tyrosine degradation. The presumed toxic agents are fumaryl- and maleylacetoacetate which are converted to succinylacetone (SA), a metabolite found in increased amounts in urine and plasma of the patients. The major clinical features are progressive liver damage and renal tubular defects with hypophosphataemic rickets. Renal tubular dysfunctions with secondary rickets may be lacking altogether, even in chronic patients. Hepatocellular carcinoma is a major cause of death in the chronic form. Diagnosis of the disorder is made by assay of SA in urine and serum and by determination of FAH in lymphocytes or fibroblasts. Prenatal diagnosis is performed by SA assay in amniotic fluid supernatant and FAH analysis in cultured amniotic fluid cells or chorionic villus material. Presence of a 'pseudodeficiency' gene for FAH prevents prenatal diagnosis by enzyme analysis in some families, and this gene also precludes identification of heterozygotes outside tyrosinaemia families. Immunoblot analyses show that acute patients and some chronic patients lack immunoreactive FAH protein. cDNA probes for FAH have been developed and several polymorphisms related to the FAH gene have been reported, which may allow prenatal diagnosis in families with complex genotypes. The gene for FAH has been mapped to chromosome 15 q23-q25. Liver transplantation is the ultimate treatment; most patients continue to excrete SA in urine after liver transplantation and therefore there is a possibility of kidney disease after transplantation. PMID- 1749222 TI - Investigation of the molecular basis of the genetic deficiency of UDP glucuronosyltransferase in Crigler-Najjar syndrome. AB - Liver biopsy samples were obtained from eight Crigler-Najjar patients. Bilirubin UDPGT activity, assayed by a microassay with HPLC analysis, was not detectable in type I livers, and low levels (9-26% of controls) of monoglucuronide conjugates only were observed in type II livers. 1-Naphthol UDPGT activity was normal in most patients, where membrane integrity was maintained by correct sample procurement and preparation. Our data on type II livers suggest that a defect in UDPGA transport is an unlikely cause of the hyperbilirubinaemia, but reduced affinity for UDPGA was observed in one sample. Analysis of four patient liver samples by immunoblot analysis revealed the heterogeneous nature of this inherited disease within the patient population, and one sample where 1-naphthol UDPGT activity was considerably reduced appeared to correlate with the non detection of a phenol UDPGT protein. Progress towards a molecular genetic diagnosis of Crigler-Najjar syndromes is discussed. PMID- 1749223 TI - Niemann-Pick disease type C: an update. AB - The concept of Niemann-Pick disease type C as a secondary sphingomyelin storage disorder (in contrast to the sphingomyelinase-deficient types A and B) has become more and more prevalent, in view of the complex lipid storage pattern and variable sphingomyelinase activities. Although the primary lesion is still unknown, studies conducted over the past six years have led to a breakthrough by showing that this disorder is characterized by unique abnormalities of intracellular translocation of exogenous cholesterol. In cultured fibroblasts of patients, this block leads to a delayed induction of the homeostatic responses to exogenous cholesterol, in particular cholesteryl ester formation, and to the accumulation of unesterified cholesterol in a vesicular, essentially lysosomal, compartment. The transport of endogenous cholesterol is apparently unaffected. The spectrum of phenotypic heterogeneity in relation to abnormal LDL-processing has been defined in a large patient population. Clinical presentation of the disease is also reviewed and biochemical correlations are discussed. This discovery has had immediate medical applications, by providing the first strategy for reliable prenatal diagnosis of the disorder and easy diagnosis of patients. To date, the exact implication of the cholesterol transport defect in the pathogenesis of Niemann-Pick type C is not known; recent observations have opened up new possible approaches for the understanding of this lesion. Although final classification of Niemann-Pick disease type C must await elucidation of the primary defect(s), present knowledge already establishes that the disease is a nosological entity distinct from Niemann-Pick disease type A and B, and suggests that it might be the model for a new molecular concept of neurolipidosis--and even of inherited metabolic disease. PMID- 1749224 TI - Paediatric liver transplantation: review of current experience. AB - During the 1980s the results of liver replacement in children improved dramatically, with 12-month survival rates rising from around 20% to over 85% at the most experienced centres. This improvement has been due to several factors, including better patient selection and timing of transplantation, advances in immunosuppressive therapy, and developments in liver preservation. Moreover, the learning curve effect has contributed with advances both in surgical technique and in the rapid diagnosis and treatment of complications, including the need to retransplant patients in whom the first graft has been irreversibly damaged. One major development is the refinement of the anatomically reduced grafts where a larger, usually adult, graft is cut down to fit a child. This has allowed a greater number of children to be grafted, including emergency cases such as fulminant hepatic failure in whom there is insufficient time to wait for a size matched donor. PMID- 1749226 TI - The place of fetal liver transplantation in the treatment of inborn errors of metabolism. AB - Over the last 16 years, 202 fetal tissue transplants have been performed in our department to treat 29 patients with severe inborn errors of metabolism without immunodeficiency, 26 patients with congenital and severe immunodeficiency diseases, and 2 patients with severe aplastic anaemia. The actuarial survival curve of patients with inborn errors of metabolism treated with fetal liver transplantation shows a 12-year survival of 77%. The condition of many of these patients has been improved by the treatment, but transplantation has had to be repeated in order to maintain clinical amelioration. Enzyme levels were not significantly and durably increased in peripheral blood but the quantities of substrates detected in sera and urines were significantly reduced and tissue deposits were stabilized. PMID- 1749225 TI - Treatment of inherited metabolic disorders by liver transplantation. AB - Among the worldwide accepted indications for liver transplantation, inherited metabolic disorders play an increasing role. In some paediatric centres this indication runs second after extrahepatic biliary atresia. The aim of liver transplantation in inherited metabolic disorders is twofold: the first is to save a patient's life, the second is to accomplish phenotypic and functional cure of his disease. These aims may be achieved in disorders presenting with cirrhosis, hepatoma, life-threatening progression or failure of other organs with preserved liver function. The timing of liver transplantation has become easier with development of surgical techniques of reduced-size donor livers. These techniques enable the performance of liver transplantation with ABO blood group compatible organs of almost any size if indicated either by deterioration of liver function or impending complications such as hepatoma or life-threatening progression. In comparison with other indications such as extrahepatic biliary atresia, postnecrotic liver cirrhosis or acute liver failure, the results of transplantation in patients with inherited metabolic disorders seem to be better, reaching up to 78-95% actuarial 1-year survival rates. However, lifelong immunosuppressive therapy is necessary. This seems to be acceptable even in disorders with only partial liver function defects. PMID- 1749227 TI - Screening and economics. AB - Screening for disease involves expenditure now in order to reap benefits in the future. It is important to understand why future benefits should be discounted in the cost-benefit calculation. The reasons are derived from a societal preference for consumption now over consumption tomorrow, combined with the productivity of capital, which enables goods today to be transformed into more goods tomorrow. It is also necessary to put costs and values on human lives. This is simplified at present in the UK because a highly restrictive immigration policy implies that the net value of the average additional citizen is zero (or even negative). The cost-benefit calculations that are presented must be carried out highly systematically in order to avoid double counting or omission. A computerized spreadsheet is ideal for this purpose. PMID- 1749228 TI - Economic evaluation of cost-benefit ratio of neonatal screening procedure for phenylketonuria and hypothyroidism. AB - A comparison between the cost of identification and care of patients with phenylketonuria (PKU) and congenital hypothyroidism (CH) and the expenditure for the care of untreated retarded patients has been established on the basis of the activity of the Nord-Pas-de-Calais regional screening centre and of interviews with patients' families. The analysis yields a benefit-cost ratio of 6.6 for PKU and 13.8 for CH prophylaxis. However, cost-benefit varies depending on the economic partner, i.e. the patient's family, Social Security or Administration. PMID- 1749229 TI - Services for thalassaemia as a model for cost-benefit analysis of genetics services. AB - Economic appraisal of genetics services is usually limited to consideration of financial costs and benefits, but this can generate misunderstandings about the aims of these services. We propose a general framework for economic analysis that includes non-financial costs and benefits, and the concept of genetic fitness. PMID- 1749230 TI - A comparison of selected phonatory behaviors of healthy aged and young adults. AB - Selected phonatory behaviors of healthy aged and young men and women were compared. Inverse-filtered air flow, electroglottograph (EGG), and intraoral air pressure signals were recorded as subjects phonated in each of four conditions: normal, soft, loud, loud/high pitched. Minimum flow offset, flow amplitude, air flow duty cycle, EGG duty cycle, estimated subglottal pressure, and fundamental frequency were derived from the recorded signals and compared among age/gender groups. Males had significantly greater flow amplitude than females regardless of age. Significant Age x Sex interactions were found for fundamental frequency and duty cycle measures. Duty cycles and fundamental frequency increased for males and decreased for females with aging. For the normal phonatory condition, aged men had significantly greater duty cycle measures, flow amplitude, and estimated subglottal pressure than young men. There were significant differences in fundamental frequency and EGG duty cycle between aged and young women during normal phonation. It was concluded that the effects of aging on phonatory behaviors are different in degree and kind for men and women. Fewer significant age-related differences in phonatory measures for women than men were consistent with reports of less age-related laryngeal degeneration in females than males. PMID- 1749231 TI - Syllabic stress and the occurrence of stuttering. AB - The occurrence of stuttering on stress-peak and unstressed syllables in connected speech was studied in 10 young adult stutterers. Results showed a significant coincidence of stutter events and syllabic stress peaks, particularly in polysyllabic words. Stuttering on the first three words of principal clauses, however, appeared independent of syllabic stress. Similarities between the loci of stutter events and segmental errors of speech are considered in relation to explanations that regard stuttering as evidence of failure in normal speech production processes. PMID- 1749232 TI - Slow-to-recover brain-injured patients: rationale for treatment. AB - Approximately 10-20% of head injury survivors sustain extensive neurological damage and remain minimally or inconsistently responsive to stimuli for 3-6 months postinjury. These patients, designated as slow to recover (STR), may be candidates for sensory stimulation programs rather than traditional rehabilitation. Medical and insurance personnel have resisted referral and payment for treatment because of the lack of objective measures of progress, a theoretical basis for treatment, and evidence of treatment efficacy. A valid, reliable assessment tool has recently been developed (Western Neuro Sensory Stimulation Profile) that assesses low-level cognitive/communicative function and documents improvement in STR patients. This article addresses the theoretical rationale for treatment. Evidence from four areas--sensory deprivation, enriched environments, nervous system plasticity, and sensitive periods of neurodevelopment--suggests that sensory stimulation programs are potentially beneficial for STR patients. Speech-language pathologists are encouraged to study the recovery patterns of STR patients and to determine the efficacy of treatment strategies. PMID- 1749233 TI - The effects of minimal pairs treatment on the speech-sound production of two children with phonologic disorders. AB - Two children whose speech-sound production could be described by phonologic processes were administered a linguistically based treatment program that utilized minimal pair words. A subset of phonemes affected by a target phonologic process was taught consecutively. Spontaneous picture-naming probes were administered periodically to measure speech-sound production for all phonemes affected by the targeted phonologic process and several control phonologic processes. For both subjects, motoric components (i.e., models and phonetic placement cues) had to be added to the minimal pairs treatment. With the added motoric components, both subjects successfully passed through all treatment steps. However, neither subject generalized modified speech-sound production to treated phonemes in untreated words or to untreated phonemes affected by the target phonologic process. PMID- 1749234 TI - Young stutterers' nonspeech behaviors during stuttering. AB - The purpose of this study was to assess the nonspeech behaviors associated with young stutterers' stuttering and normally fluent children's comparable fluent utterances. Subjects were 28 boys and 2 girls who stutter (mean age = 54 months) and 28 boys and 2 girls who do not stutter (mean age = 54 months). Each child and his or her mother were audio-video recorded during a loosely structured, 30-min conversation. Sixty-six different nonspeech behaviors associated with 10 randomly selected stutterings per stutterer and 10 comparable fluent utterances per normally fluent child were assessed by means of frame-by-frame analysis of the audio-video recordings. Results indicate that (a) young stutterers produce significantly more nonspeech behaviors during stuttered words than do normally fluent children during comparable fluent words, (b) young stutters produce significantly more head turns left, blinks, and upper lip raising during stuttered words than do normally fluent children during comparable fluent words, and (c) talker group membership could be significantly determined on the basis of certain types of nonspeech behaviors despite considerable overlap in frequency and type of nonspeech behavior between the two talker groups. Findings suggest that children can be classified as stutterers on the basis of their nonspeech behaviors and that these behaviors may reflect a variety of cognitive, emotional, linguistic, and physical events associated with childhood stuttering. PMID- 1749235 TI - Effects of long-term tracheostomy on spectral characteristics of vowel production. AB - This study investigated the effects of long-term tracheostomy on the development of speech. Eight children who underwent tracheotomy during the prelingual period were compared to matched controls on selected spectral parameters of the speech acoustic signal and standard measures of oral-motor, phonologic, and articulatory proficiency. Analysis of formant frequency values revealed significant between group differences. Children with histories of long-term tracheostomy showed reduced acoustic vowel space, as defined by group formant frequency values. This suggests that these children were limited in their ability to produce extreme vocal tract configurations for vowels (a,i,u) postdecannulation. Oral motor patterns were less mature, and sound substitutions were not only more variable for this group, but also reflected a persistent overlay of maladaptive compensations developed during cannulation. PMID- 1749236 TI - Assessment of the dynamics of vocal fold contact from the electroglottogram: data from normal male subjects. AB - Electroglottographic (EGG) and acoustic records from 10 normal men prolonging the vowel /a/ at 60-68 dB, 70-78 dB, and 80-88 dB SPL were obtained. "Contact quotient" (EGG duty cycle) was shown to vary directly with vocal SPL. The mean contact quotient was 0.57 (SD = 0.07) and varied on the order of 1% over the course of a given phonation. "Contact index", a metric of EGG symmetry, also tended to vary with SPL. Consistent with previous qualitative descriptions of EGG morphology in modal register voice, the contact index averaged -0.52 (SD = 0.08), indicating that the EGG "closing phase" represents about 24% of the entire "contact phase". Contact index was more variable than contact quotient on consecutive EGG waves, varying by about 10% during phonation. Subjects were also instructed to produce a slow crescendo. Sound pressure and EGG data indicated that both the slope of increasing EGG contact and EGG duty cycle were significantly related to the amplitude of the acoustic signal. These results suggest that quantitative electroglottography may provide powerful insights into the control and regulation of normal phonation and into the detection and characterization of pathology. PMID- 1749237 TI - Accuracy of the pressure-flow method in estimating induced velopharyngeal orifice area: effects of the flow coefficient. AB - A two-part study was conducted to determine the accuracy of the pressure-flow method in estimating induced velopharyngeal orifice areas when the flow coefficient k was empirically determined. In Study 1, short tubes, 4.5 cm in length and with internal diameters of 3.2, 4.8, and 6.4 mm, were placed in a model of the vocal tract, and the associated flow coefficients were calculated. In Study 2, the 4.8-mm internal diameter tube was inserted into the nasopharynx of a normal adult subject to induce oronasal coupling during production of the syllable/pa/. Results for the human subject revealed that the error between the known and estimated orifice areas was approximately 7%. This finding indicates that the pressure-flow technique is accurate when the flow coefficient of the orifice is known. It is suggested that future research attempt to estimate flow coefficients associated with the geometry of the human velopharyngeal orifice in order to improve the accuracy of the pressure-flow technique. PMID- 1749238 TI - Research design issues in relationships between anxiety and stuttering: comments on Craig. PMID- 1749239 TI - Response to Perkins, "What is stuttering?". PMID- 1749240 TI - Responses to requests for conversational repair by adults with mental retardation. AB - This study focused on adjustments made in conversation in response to listener feedback. Subjects consisted of 22 community-based and 22 institutionalized adults with mental retardation individually matched for full-scale IQ. For each subject, data were collected in a dyadic conversation with an investigator. During the course of the conversation, the investigator introduced stacked sequences of three requests for clarification of the same message ("Huh?" "What?" "What?"). Each subject's responses to these requests were analyzed. Results indicated that community-based subjects used certain sophisticated repair strategies more often than did their institutionalized peers. However, neither group of subjects was as responsive to the requests for clarification as would have been predicted considering their general levels of intellectual and linguistic functioning. PMID- 1749241 TI - Predicting poor-communication status in preschool children using risk factors present at birth. AB - The speech and language status of 662 children between the ages of 30 months and 5 years was determined through the use of parent report information. Twelve of these children were reported by their parents to have been diagnosed as having a speech-language disorder, and 50 of these children were found to be at or below the 10th percentile in language development for children of their age. Information about family background and birth history obtained when these children were born was evaluated with respect to its power to predict speech language status in these preschool children. A set of risk criteria was found to accurately predict 55% of those children with poor communication skills and 76% of those with normal communication development. This prediction was improved by the addition of data about the child's birth order. These results suggest that programs of preschool identification should consider the inclusion of a registry of children who are at risk for a communication disorder. PMID- 1749242 TI - The continuity of babble and speech in children with specific expressive language delay. AB - A natural language sample of babble and words was obtained for 37 two-year-olds with severe specific expressive language delay. Variables derived from this sample were used to predict individual differences in expressive language scores 5 months later. The rate of word use was positively related to language outcome, whereas rate of vowel babble was negatively related to outcome. Together, these two variables accounted for 41% of the variance in language outcome test scores. The addition of one nonlinguistic variable, a measure of behavior problems, allowed the prediction equation to account for over 50% of the variance in expressive language outcome. The single strongest correlate of language outcome was the proportion of consonantal to vowel babble. The degree of social responsiveness of babble and the length of babble were not related to later language scores. These findings indicate that for children with specific expressive language delay, vowel babble competes with expressive language, consonantal babble facilitates expressive language, and the length and social responsiveness of babble are independent of expressive language. The continuity between babble and speech is multidimensional and multidirectional. PMID- 1749243 TI - Verb particle and preposition acquisition in language-impaired preschoolers. AB - This study examined the acquisition of verb particles and prepositions in language-impaired, language-matched, and age-matched preschool children. A videotape experimental task, in which subjects viewed and described brief action sequences, was implemented. The videotape task included particle, preposition, full noun phrase, and pronoun noun phrase items for six different particle/preposition words. Primary results indicated that the use of verb particles constituted a particularly challenging linguistic task for the language impaired subjects relative to both their age- and language-matched peers. These results suggest multiple sources of difficulty for language-impaired children in the acquisition of grammatical form classes. Lexical and grammatical difficulties, as well as possible processing limitations, are implicated. PMID- 1749244 TI - Redundancy enhances emotional inferencing by right- and left-hemisphere-damaged adults. AB - This study investigated the influence of enhanced textual redundancy on affective interpretations made by unilaterally right or left hemisphere brain-damaged adults and normally aging control subjects. Emotional interferences were drawn from linguistic or prosodic material, and redundancy effects were examined within and across stimulus boundaries. Results indicate that heightened semantic redundancy improved the accuracy of linguistic and prosodic judgements of affect for all groups. Correct prosodic judgements were also made more quickly by a subset of each group when textual redundancy was maximized. The facilitory influence of increased redundancy was not attributable solely to perseveration or response rigidity. Possible mechanisms by which semantic redundancy affects cognitive processing are considered. PMID- 1749245 TI - Family history in developmental expressive language delay. AB - Familial aggregation of language deficits has been demonstrated in previous studies. However, researchers have typically failed to differentiate subgroups of language-impaired children. The present study used questionnaire data to assess the family history of speech, language, and school problems in a group of young children with developmental expressive language delay (ELD) and in a sample of normally developing children. In contrast to previous studies of language and speech problems, no strong familial component of ELD was found. Further, family history was not predictive of later language development in ELD children. These findings argue against genetic and familial causes of ELD and attest to the importance of differentiating subtypes of early language problems. PMID- 1749246 TI - Otitis media in early childhood and later language. AB - The relationship between early otitis media with effusion (OME) experience and later language development was examined in a prospective cohort study of 30 children from middle-class families and 33 children from low-income families. Ear status was monitored using otoscopy and tympanometry during wellness and illness periods between birth and 3 years of age. Language was assessed using standardized tests and a language sample between 4 1/2 and 6 years. Findings suggested no reliable relationship between early OME experience and later language development. PMID- 1749247 TI - Very-low-birthweight children and speech and language development. AB - Very low birthweight (VLBW) is often considered to be a risk factor for speech and language disorders, yet data are equivocal. The present study compared speech and language comprehension and production between 249 very-low-birthweight (VLBW: less than 1.5 kg) and 363 normal-birthweight 8-year-olds, randomly sampled in a geographic area. Mean performance for the entire group of VLBW children and for the group when 24 VLBW children with major neurologic abnormalities were excluded, was significantly lower than for controls on the majority of speech and language measures. Further analyses addressed the clinical significance of these statistically significant differences. Test scores were converted to standard scores and grouped according to standard deviation intervals, thus portraying each child's performance in terms of the magnitude of discrepancy from each test's mean. When the 24 children with major neurological abnormalities were excluded, no significant differences between the VLBW and control children were observed. Using discrepancy between WISC-R performance IQ and language to define specific language impairment (SLI), a higher percentage of control than VLBW children were identified as having SLI. Neonatal risk factors did not differentiate between VLBW children with or without SLI. A higher proportion of VLBW than control children did present subnormal language associated with IQ less than 85, hearing deficits, and/or major neurological impairments. Thus, SLI is not more common among VLBW than control children. Language deficits accompanied by more general developmental problems, however, are more frequent. PMID- 1749248 TI - Effects of different frequency response strategies upon recognition and preference for audible speech stimuli. AB - The purpose of this study was to examine whether the amount of low- versus high frequency amplification should change as a function of input level, as is done in some recently developed hearing aids. Adults with high-frequency sensorineural hearing loss served as subjects. Both identification performance and preference judgments for audible CV syllables were assessed as a function of input level for three different signal processing conditions both in quiet and in noise. The first signal processing condition was a conventional high-pass frequency response that did not change its transfer function as the input level increased; the second condition was similar to a typical adaptive frequency response (AFR) hearing aid: a high-pass frequency response that became increasingly high-pass as the input level increased; the third condition was similar to the K-Amp hearing aid recommended by Killion (1988): a high-pass frequency response that became more broadband as the input level increased. Results indicated no significant differences among the three different processing conditions for syllable recognition and a strong listener preference for the syllables presented via the conventional amplification scheme. PMID- 1749249 TI - Test-retest reliability in tympanometry. AB - Test-retest reliability for tympanometric measures was evaluated across five sessions in 20 subjects with normal hearing and normal middle-ear function. Tympanograms were obtained on each ear for probe frequencies of 226, 678, and 1000 Hz using both ascending and descending directions of pressure change. Across all conditions, the tympanometric measure that consistently demonstrated the highest test-retest reliability was compensated static acoustic admittance. Test retest correlations for peak compensated static acoustic admittance measures were higher than those for ambient measures across all probe frequencies and both directions of pressure change; the differences in correlations for peak and ambient measures, however, reached significance only for 226-Hz conditions. Across-session correlations for tympanogram width did not differ significantly for measures referenced to the lowest tympanogram tail and those referenced to +200 daPa. PMID- 1749250 TI - Conductive hearing loss during infancy: effects on later auditory brain stem electrophysiology. AB - Long-term effects on auditory electrophysiology from early fluctuating hearing loss were studied in 27 children, aged 5 to 7 years, who had been evaluated originally in infancy. For controls (Group A), infant auditory brain stem responses (ABRs) were normal from birth to age 2 years. A second group (Group B) had intermittent conductive hearing loss. A third group (Group C) had more abnormal ABRs during infancy than Group B and more severe and frequent conductive hearing loss. For this follow-up study, all children had normal peripheral hearing at test. ABRs were obtained to monaural and binaural stimuli. Binaural interaction (BI) in the ABR was assessed in difference traces, derived by subtracting summed binaural from summed monaural waveforms. Controls differed from both groups with early hearing loss for wave III and wave V latencies and interpeak I-III and I-V latencies. There was a significant difference in the presence of BI. Eight of 9 A subjects and 8 of 9 B subjects, but only 4 of 9 C subjects, had demonstrable BI. Findings suggest that early fluctuating hearing loss disrupts later auditory brain stem electrophysiology. PMID- 1749251 TI - Clinical applications of otoacoustic emissions. AB - On the basis of recent advances in auditory physiology, new tests of cochlear function have been developed using measures of otoacoustic emissions. In the present report, the clinical potential for each of the four basic emission types is examined. In addition, the practical advantages of examining the ear with two specific types of evoked emissions, transiently evoked and distortion-product otoacoustic emissions, are reviewed in detail. Finally, the future role of tests of otoacoustic emissions in the diagnosis of hearing impairment is discussed. The current view is the evoked emissions hold promise as an essential part of the clinical examination of the auditory system. PMID- 1749252 TI - Maternal linguistic input to toddlers with slow expressive language development. AB - Maternal speech styles to children between 20 and 34 months of age who were slow to acquire expressive language were compared to those of mothers with normally speaking toddlers. Aspects of the mothers' speech examined included use of various sentence types (declaratives, negative, questions, etc.); the mother's lexical contingency with regard to the child's utterance; mother's use of pragmatic functions such as requests, comments, and conversational devices; and the mother's use of topic management. Results revealed that mothers of toddlers with slow language development are different from mothers of normal speakers only in their frequency of use of lexical contingency devices, specifically, expansion and extension. However, the proportion of expansions and extensions relative to the number of child utterances is not different, indicating that when late talkers give their mothers something to expand, the mothers do so, but that the late talkers do not give their mothers as much speech to work with as do the normal toddlers. Implications of these findings for parent training are discussed. PMID- 1749253 TI - Interobserver reliability using the Phonetic Level Evaluation with severely and profoundly hearing-impaired children. AB - This study examines whether observers reliably categorize selected speech production behaviors in hearing-impaired children. A group of experienced speech language pathologists was trained to score the elicited imitations of 5 profoundly and 5 severely hearing-impaired subjects using the Phonetic Level Evaluation (Ling, 1976). Interrater reliability was calculated using intraclass correlation coefficients. Overall, the magnitude of the coefficients was found to be considerably below what would be accepted in published behavioral research. Failure to obtain acceptably high levels of reliability suggests that the Phonetic Level Evaluation may not yet be an accurate and objective speech assessment measure for hearing-impaired children. PMID- 1749254 TI - A simple model of host-parasite evolutionary relationships. Parasitism: compromise or conflict? AB - The evolutionary biology of host-parasite relationships are considered here using a simple game-theory model in which hosts play against parasite and vice versa. In this model, the players can choose between two strategies (aggressive or not aggressive) and the utility of the game is envisaged in terms of fitness and selective costs. The game solutions suggest that the two types of confrontation are encountered in symbiotic relationships and thus constitute two Evolutionary Stable Strategies (ESS). These observations lead us to discuss: (i) the status of different kinds of symbiotic relationships (i.e. parasitoidism; parasitism, commensalism and mutualism) related to selective costs and (ii) the position of coevolution in this game theory context. PMID- 1749255 TI - Counting phylogenetic invariants in some simple cases. AB - An informal degrees of freedom argument is used to count the number of phylogenetic invariants in cases where we have three or four species and can assume a Jukes-Cantor model of base substitution with or without a molecular clock. A number of simple cases are treated and in each the number of invariants can be found. Two new classes of invariants are found: non-phylogenetic cubic invariants testing independence of evolutionary events in different lineages, and linear phylogenetic invariants which occur when there is a molecular clock. Most of the linear invariants found by Cavender (1989, Molec. Biol. Evol. 6, 301-316) turn out in the Jukes-Cantor case to be simple tests of symmetry of the substitution model, and not phylogenetic invariants. PMID- 1749256 TI - Frequencies of codons in histones, tubulins and fibrinogen: bias due to interference between transcription signals and protein function. AB - The distribution of codons was studied in 65 proteins: 48 histones, 14 tubulins, and three fibrinogens, With the methodology used, (1) we confirmed that the preterminator state of a codon has no detectable effect on codon bias. (2) The well-known effect of CG suppression was visible. We also found that (3) some codons which are very rare, are equal to parts of known transcription signals. Thus, we advanced that to avoid signal interference, the use of these codons is suppressed when a synonymous codon is available. In addition we found that in the whole series of codons, transcription signals are less frequent than in a random sequence of equal composition. Finally we observed (4) that tryptophan is absent in histones. This absence was related not to the TGG codon itself, but to characteristics of the amino acid. We conclude that the functional constraints of a protein can influence, at least for synonymous codon usage, the evolution of its own coding sequence. PMID- 1749257 TI - Evolution of split genes. PMID- 1749258 TI - The world's current situation on development of traditional Chinese medicine and its prospects. PMID- 1749259 TI - Combined application of scalp and body acupuncture in the treatment of pseudobulbar paralysis. PMID- 1749260 TI - Treatment of headaches by acupuncture and Chinese herbal therapy--conclusive data concerning 1000 patients. PMID- 1749261 TI - Deep puncture of renying point in the treatment of cerebrovascular disease with sequalae--a report of 89 cases. PMID- 1749262 TI - Magnetic disk applied on Neiguan point for prevention and treatment of cisplatin induced nausea and vomiting. PMID- 1749263 TI - Treatment of papillo-retinitis and uveitis associated with cat-scratch disease by combination of TCM and modern drugs. PMID- 1749264 TI - Treatment of urinary retention with acupuncture and moxibustion. PMID- 1749265 TI - Anti-hypertensive effect of auriculo-acupoint pressing therapy--clinical analysis of 274 cases. PMID- 1749266 TI - 408 cases of urinary calculus treated by auriculoacupoint pressure. PMID- 1749267 TI - 42 cases of climacteric syndrome treated with auricular pellet pressure. PMID- 1749268 TI - Treatment of urinary retention due to postoperative anal pain. PMID- 1749269 TI - Massage for the treatment of voice ailments. PMID- 1749270 TI - Advances in researches on auriculo-acupoints. PMID- 1749271 TI - [Clear cell carcinoma of the female genital tract]. AB - From 1980 to 1989 clear-cell carcinoma was diagnosed in 66(4.2%) out of 1562 adenocarcinomas of the female genital tract: in the ovary, 2.9% in the endometrium, 9.8% in the uterine cervix; 4.5% in the vagina, and 1.9% in the Fallopian tube. The diagnosis was made at clinical stage I in 26.9% of cases located in the ovary, 62.5% in the endometrium, and 42.8% in the uterine cervix. At stages III and IV the highest percentage of cases was diagnosed in the ovary 42.3% and 26.9%, respectively. The material was divided into the histological subtypes, and the glandular papillary was found in 54.5%, the tubulocystic in 31.8% and the solid in 13.6% of cases. The tubulocystic subtype showed the best prognosis, with the 50% five-year survival rate, while the glandular papillary subtype had 38.1%, and the solid subtype a 14.3 five-year survival rate was 66.6% for the ovary, 85% for the endometrium and 75% for the uterine cervix. For all other stages together (II, III, IV), the five-year survival rate was 0% for the ovary, 20% for the endometrium and 0% for the uterine cervix. PMID- 1749272 TI - [Bioethics in neonatology]. PMID- 1749273 TI - [Evaluation of embryotoxicity of materials used in the IVF laboratory]. AB - It has been established that the quality of water for the preparation of culture media has an essential influence on the percentage of two cell-stage mouse embryos developing successfully until the blastocyst stage. The quality of media prepared with bidistilled water (p less than 0.001) is inferior to that prepared with bidestilled demineralized water (p less than 0.02). Best results were attained by using the medium prepared with Nanopure water (Barnstead), in which 73.2% of embryos developed into blastocysts. There was no statistically significant difference between this medium and the commercial liquid medium (Sigma), in which 83.1% of embryos developed into blastocysts. The age of the medium and the percentage of added serum have no statistically significant influence on the outcome of the test. Contact of the medium with the syringe containing a black rubber piston proved explicitly embryotoxic (p less than 0.001). PMID- 1749274 TI - [Levels of estrogen and progesterone receptors in premalignant and malignant states in the endometrium]. AB - In a prospective study conducted from 1981 to 1989, concentrations of estrogen (ER) and progesterone (PR) receptors were determined by the saturation analysis of cytosols prepared from 67 samples of human endometrial tissue. Patients over 35 years of age who had come to the hospital because of irregular bleeding were included in the investigation. In the group examined it was found that 25 patients developed endometrial carcinoma, 22 hyperplasia adenomatosa and 20 patients had normal pathohistological findings. The median values of ER concentrations were 46, 99 and 31 fmol/mg of protein, with the ranges of 0-628, 0 2348 and 0-552 fmole/mg of protein in the group with normal endometrial tissue, hyperplastically transformed endometrial tissue and in the group with endometrial carcinoma, respectively. The median values of PR concentrations were 196, 307 and 96 fmol/mg of protein, with the ranges of 0-1714, 0-2402 and 0-582 fmole/mg of protein in the group with normal endometrial tissue, hyperplastically transformed endometrial tissue and in the group with endometrial carcinoma, respectively. In the group of patients with endometrial carcinoma 40% of ER+/PR+ tumors (greater than 50 fmole/mg of protein), 36% of ER-/PR-tumors, and 24% of ER-/PR+ tumors were found. The results of the median test showed that there were no statistically significant differences among ER concentrations (chi 2 = 2.822; P = 0.2439), or among PR concentrations (chi 2 = 3.582; P = 0.1668) in the groups of patients examined. PMID- 1749275 TI - [Pregnancy outcome after early amniocentesis]. AB - The indications, karyotype, and outcome of 1812 pregnancies following midtrimester amniocentesis (eACZ/as) performed from 1977 to 1989 are presented, especially regarding the risk of pathologic karyotypes and spontaneous abortion. There were 37 pathologic karyotypes (trisomy 21 in 24 pregnancies). The spontaneous abortion rate following amniocentesis was 2.8% although it was almost halved after direct ultrasound guidance had been introduced (1.87% versus 3.66%). In gravidas with previous spontaneous abortion, the preterm delivery rate and spontaneous abortion rates following rACZ were significantly increased. There is a progressive increase of the spontaneous abortion rate after eACZ with the number of previous spontaneous abortions; 5.83% when there was only 1 previous spontaneous abortion, 7.83% when there were 2, and 8.75% when there were 3 or more spontaneous abortions. Previous spontaneous abortions do not increase the risk of chromosomal aberration. In women aged 37 years or more the risk of trisomy 21 is 0.69%, aged 38 years 1.55% and over 39 years 0.44%. The risk is rapidly increasing after 40 years of age (2.25%). The proportion of pathologic karyotypes in these age groups was significantly higher in comparison to younger women. The age limit of 37-38 years as the indication of a possible appearance of mid-trimester ACZ is discussed. PMID- 1749276 TI - [Correlation between weather factors and the number of premature and yearly births]. AB - In a retrospective study for a period of five years, a total of 41,760 births in Sarajevo were analysed. For the same period, also meteorological data, such as air temperature, humidity, rain, cloudiness, barometric pressure, were gathered, by determining the weather type for each day. Using computer analyses, daily weather types with the number of births were compared. On the basis the statistical method of Friedman's test it is concluded that there is a significant correlation (p less than 0.05) between the weather types and the daily number of births. By comparing the daily number of births with the weather type of the preceding day the same conclusion was drawn. A cyclic fluctuation was also observed in the number of human births: the increased number of births in the December-January period and the decreased number of births in the August September period. Premature births did not show any cyclic pattern. PMID- 1749277 TI - [Comparison of prostaglandin E2 and oxytocin infusions for induction of labor in primiparas at term with an unripe cervix and premature rupture of fetal membranes]. AB - The study aimed at examining the effectiveness of labor induction in term pregnant nulliparas with the premature rupture of the membranes (PRM) and unriped cervix (Bishop less than 6). Each group contained 17 nulliparas. In the first group the labor was induced with the prostaglandin E2 (PgE2) infusion, in the second group the oxytocin infusion was used. The results of both groups were compared. PgE2 was found to be effective in labor induction; the rate of caesarean sections was 18.75% in the first group and 29.41% in the second group. The PgE2 drug was found to be safe for the fetus and also well tolerated by pregnant women. The effect of the drug on the ripening of the cervix has not been noticed. The time interval from the induction of labor to the delivery is equal in both groups. However, in the first group significantly less work was done by the uterus at the same interval. No incidence of uterine hyperactivity was recorded. All newborns in the first group were in good condition: in the second group two cases of fetal distress were recorded. The pregnancy outcome shows that the PgE2 drug is superior to oxytocin for labor induction in term pregnant nulliparas with the PRM and unriped cervix. PMID- 1749278 TI - [Correlation between levels of prolactin in maternal serum, fetal serum and amniotic fluid in childbirth at term]. AB - In 117 parturients with 38-41 gestation weeks, prolactin was analysed by the radioimmunologic method in the mother serum, the umbilical cord serum and vein, and in the amnionic fluid. Three groups of parturients and their newborns were examined: the group (n = 44) with the birth having started spontaneously with the appearance of labour pains 1/10 minutes, the group (n = 38) with a programmed birth induced by the infusion of oxytocin, and the group (n = 35) with the birth comprising elective cesarean section. The concentration of prolactin in the examined sera is characterized by considerable individual oscillations. The highest prolactin level was in the amnionic fluid (395.6 +/- 130.1 mu/L) and the lowest in the mother serum (174.6 +/- 84.1 mu/L) which shows a statistically significant difference (p less than 0.01). Prolactin values in the umbilical artery (244.6 +/- 98.3 mu/L) and vein (230.4 +/- 91.7 mu/L) are significantly (p less than 0.001) higher than the value in the mother sera and significantly lower (p less than 0.001) than the prolactin concentration in the amnionic fluid. The difference of the prolactin values in the sera of the umbilical cord blood vessels has no statistical significance (p greater than 0.05). Nor is there any statistically significant difference between prolactin concentrations in spontaneous and induced deliveries versus those in deliveries terminated with elective cesarean section (p greater than 0.05). A correlation analysis of the functional connection of prolactin in the sera of the mother, fetus, and amnionic fluid gives the correlation coefficient values of high statistical significance (0.482 less than r less than 0.906; p less than 0.001). PMID- 1749279 TI - [Relation between fetal hypoxia, neonatal asphyxia and hypoxic-ischemic encephalopathy]. AB - Clinical data, duration of labour, mode of delivery and possibilities of fetal heart rate monitoring in predicting perinatal asphyxia and neonatal encephalopathy in 143 consecutively delivered asphyxiated infants and 143 paired healthy infants are analyzed. Perinatal asphyxia occurred in only 2.6% of normal pregnancies and significantly more frequently in pregnancies complicated by gestosis. It is far more common in children subject to operative deliveries (15 20%) and when labour lasts longer than 12 hours, either in vertex or breech presentations. The occurrence of encephalopathy is less frequent in children delivered by cesarean section (1.6%) and almost three times more frequent than in vaginal breech deliveries. In asphyxiated children delivered vaginally, significantly more frequently CTG scores were prepathologic (38% versus 3.4%). In the cesarean section group the differences are not significant in prepathologic CTG scores but are highly significant when CTG scores were pathologic (36% versus 2.7%). The mean duration of the pathologic heart rate pattern is significantly longer in mild asphyxia in comparison to the control group (45 minutes versus 12.5 minutes). In moderate asphyxia the pathologic CTG pattern lasted 72.1 minutes and in severe asphyxia 52 minutes. PMID- 1749280 TI - [Preservation and relocation of the ovaries in an experiment on female dogs and the initial experience in radical hysterectomy in women]. AB - During an experiment in bitches, the ovaries were placed sub-peritoneally beneath the skin of the abdominal wall preserving the infundibulo-pelvic ligament. A year later a relaparotomy was performed. No alterations were evidenced in the ovaries placed either sub-peritoneally of beneath the skin. In 7 patients of less than 36 years of age, during radical hysterectomy performed for cervical carcinoma the ovaries were placed intraperitoneally at the level of the lower kidney pole, preserving the vascularisation of the infundibulo-pelvic ligament. In one patient a cystic degeneration occurred on the right side, while the ultrasound control did not reveal any pathology in the rest of the patients. A year later the total urine estrogen levels were within normal ranges. PMID- 1749281 TI - [Evaluation of short-term exposure to a polyacrylonitrile cervical dilator in preabortion preparation of the uterine cervix in adolescent girls]. AB - Authors investigated possibilities of application of polyacryl-nitrile cervical dilators PCD-Dilapan in preabortion preparation of the cervix during the first trimester of pregnancy in 39 adolescent patients. Control of the achieved degree of cervical dilatation was performed by largest No Hegar dilator which did not show resistance during insertion. The control group comprised 35 adolescent patients in whom cervical dilatation was performed only by Hegar dilators till optimal dilatation for vacuum aspiration was achieved. Mean cervical dilatation in the investigated group was means = 8.85 mm (SD +/- 0.85) and in the control group means = 8.55 mm (SD +/- 0.78) with no statistically significant difference (T = 0.024, p greater than 0.05). "Analogous visual scale" was used for pain estimation during cervical dilatation. In the investigated group means = 2.01 (SD +/- 1.83) of pain degrees while means = 6.71 (SD +/- 1.89) in the control group. Side effects during cervical dilatation were noted in 15.38% of patients in the investigated group and in 51.41% of patients in the control group which difference was not statistically significant (chi 2 = 5.59, p greater than 0.05). PMID- 1749282 TI - [Sterilization--where are we and what do we want?]. AB - According to the estimation from the mid-eighties, about 135 million people were sterilized, 95 million females and 40 million males. In 1977, sterilization was legalized in Slovenia, in 1978 in Croatia. In the period from 1978 to 1989, 4,503 females and 654 males were sterilized in Slovenia. The majority of female sterilizations were performed in the interval and post partum (the third cesarean section), applying laparoscopy or mini-laparotomy according to Pomeroy, in some cases the obsolete Madlener technique, while vasectomies were performed by using the standard method. The accurate statistical data on complications are not available but are estimated to be minimal. Requests for a tubal or seminal duct reconstruction have been exceptional. With a higher number of sterilizations the incidence of induced abortions in women at the age of more than 35 years would be reduced and the use of contraception would be increased. Yugoslavia, besides Albania and the Soviet Union, was the last to resort to contraceptives. PMID- 1749283 TI - [The HELLP syndrome--a case report]. AB - A 31-year-old secundipara with eclampsia developed the HELLP syndrome after delivery. Clinically, along with very high blood pressure values (29.3/17.3 kPa) and eclamptic attacks, an intense pain in the upper abdomen and nausea were dominant. The patient also had severe thrombocytopenia (18 x 10(9)/L), hemolysis, and increased liver enzymes (SGOT up to 220 U/L and SGPT up to 100 U/L). An intensive therapy, including--together with usual interventions in serious EPH gestoses--also plasmapheresis, antithrombin III substitution, freshly frozen plasma, and transfusion of blood and thrombocytes, proved successful in achieving the normalization of the blood pressure, blood count and liver enzymes, as well as a clinical improvement, so that 18 days after delivery it was possible for the patient to go home, provided with necessary instructions. PMID- 1749284 TI - [Malignant ovarian tumors in childhood and adolescence in Novi Sad (1946-1989)]. AB - In the period from 1946-1989, at the Department of Gynecology and Obstetrics University of Novi Sad, 79 ovarian tumors in children and adolescents were registered. There were 10 (12.6%) malignant tumours. The most common were dysgerminoma and carcinoma (total 6-7.6%). The treatment depended on the extent of the disease at the time of diagnosis (surgery, irradiation, chemotherapy or combination). PMID- 1749285 TI - [Anterior pelvic exenteration with ileocystoplasty in advanced cancer of the uterine cervix]. AB - A female patient with the IV grade cervical carcinoma without distant metastases is presented. The patient underwent a radical surgical intervention. An anterior pelvic exenteration with ileocystoplasties was successfully performed. The patient is alive 14 months after the initial treatment. No greater complications were observed during the operation and after it, but in spite of a satisfactory general status, the patient has had nocturnal incontinence all the time. It is believed that this complication is the sequel of the newly formed urinary bladder, as the convolution of the ileum is only 30 cm long which has proved insufficient. PMID- 1749286 TI - [Atypical cervical cytology during pregnancy in the region of Baranja]. AB - In the period from 1985 to 1989, 2521 pregnant women, making up 18.7% of women in fertile age, were controlled in antenatal surgeries in the area of Baranja. In 73 (2.9%) women a cytologic picture of cervical atypia was found: in 2.1% of them there was a cytologic picture of light and moderate dysplasia (group IIIA), in 0.6% a picture of severe dysplasia (group IIIB), and in 0.2% pregnant women there was a picture of carcinoma in situ (group IV). Progression of cytologic findings into a higher stage was noted in 23.3% women, persistence was recorded in 21.9% and regression in 54.8% women. A total of 71.2% pregnant women with the cytologic atypia of the cervix were colposcopically examined. An abnormal colposcopic picture was found in 65.4% of them. By the end of the puerperium histologic verification was made in 38.4% cases and 61.6% were controlled only cytologically and colposcopically. By means of histologic examination of the tissue specimen, progression of an intraepithelial lesion into an invasive carcinoma was not found in any of the women. These results corroborate the point of view that in pregnant women with the cytologic atypia of the uterine cervix the histologic verification can be postponed until after the delivery without any considerable risk. Only in the case of a cytologic or colposcopic suspicion of invasion it is necessary to verify the finding histologically. PMID- 1749287 TI - Surgical management of hepatic hydatid disease. AB - The use of conservative or radical surgical procedures in the management of hepatic echinococcosis is controversial. A review of data on 23 patients with hydatid cysts of the liver that were diagnosed between 1935 and 1990 at our institution was undertaken to determine the safety and efficacy of various surgical procedures. In eight patients (group 1), the cysts were treated conservatively by instillation of a scolicidal agent followed by evacuation of the cyst, drainage, or omentoplasty of the residual cyst cavity. Thirteen patients (group 2) underwent radical excision of the cyst by either pericystectomy or hepatic resection. In addition, two patients were treated by combined techniques. Scolicidal agents were used in 18 patients (78%) and apparently resulted in caustic biliary injury and death in 2 patients. Group 1 and group 2 patients had similar complication rates (62% and 54%, respectively) and mean hospital stay (24 and 23 days, respectively). Recurrent cysts, however, were detected in three of six patients who underwent a conservative surgical procedure and participated in follow-up, whereas no patients treated by a radical procedure had a recurrence. Because pericystectomy and hepatic resection resulted in a low rate of recurrence and eliminated the need for use of potentially toxic scolicidal agents, these procedures may be the preferred method for the surgical management of hepatic hydatid disease. PMID- 1749288 TI - Levels of lipids, lipoproteins, and apolipoproteins in a defined population. AB - As part of a large cross-sectional investigation--the Rochester Family Heart Study--plasma levels of lipids, lipoproteins, and apolipoproteins were measured in a sample from the general population of male and female subjects who ranged in age from 5 to 90 years. Polyclonal radioimmunoassays developed at the Mayo Clinic were used for measurement of apolipoproteins A-I, A-II, C-II, C-III, and E, whereas a monoclonal enzyme-linked immunosorbent assay was used for apolipoprotein B. On the basis of 984 subjects who reported that they were fasting, were not pregnant, had never smoked, and were taking no medications thought to influence lipid levels, we determined age- and gender-specific percentiles for plasma levels of cholesterol, triglycerides, high-density lipoprotein cholesterol, and six apolipoproteins. These percentiles will facilitate identification of persons who are in the highest and lowest percentiles for their age and gender. The levels of the apolipoproteins varied for both age and gender. This is the first study to provide a reference sample for plasma levels of these apolipoproteins for male and female subjects 5 to 90 years of age selected from the general population. PMID- 1749289 TI - Magnetic resonance imaging of the hand, wrist, and forearm: utility in patients with pain and dysfunction as a result of trauma. AB - We reviewed the clinical data, results of imaging studies, and surgical pathologic correlations in 41 consecutive patients with pain in the hand, wrist, or forearm to evaluate the role of magnetic resonance imaging in comparison with that of other imaging techniques. Of the 41 patients, 24 had a trauma-related lesion. In 18 of these 24 patients, the findings on magnetic resonance imaging were equivalent to (6 cases) or better than (12 cases) the clinical findings or the findings on other imaging studies for the detection of lesions of the hand, wrist, or forearm. Moreover, the results of magnetic resonance imaging affected the clinical management in 7 of the 24 cases (29%). PMID- 1749290 TI - The evolution of Hodgkin's disease and necrobiotic xanthogranuloma syndrome. AB - We describe a woman in whom hypogammaglobulinemia and severe granulomatous cutaneous lesions had developed during childhood; subsequently, Hodgkin's disease and necrobiotic xanthogranuloma were diagnosed. This case illustrates an apparent association with disease activity and raises the question of a direct relationship of necrobiotic xanthogranuloma with lymphoproliferative disease. PMID- 1749291 TI - The potential for muscarinic receptor subtype-specific pharmacotherapy for Alzheimer's disease. AB - In several neurodegenerative disorders, including Alzheimer's disease, a loss of the cholinergic projections of the basal forebrain to the cerebral cortex and hippocampus occurs. Studies of the anatomic and physiologic characteristics of these ascending cholinergic systems suggest that they are important in processing information and in memory function. Muscarinic receptors are situated at various critical control points in these pathways. Activation of postsynaptic muscarinic receptors often increases the excitability of neurons; thus, the signal-to-noise ratio for sensory processing is enhanced. In addition, muscarinic receptors negatively control cholinergic tone at presynaptic sites. Molecular biologic methods have disclosed the existence of five muscarinic receptors, which are coupled to different second messenger systems. The evidence reviewed suggests that at least four of the five muscarinic receptor genes are expressed as functional receptor proteins in the neocortex and hippocampal formation. On the basis of the current information about their pharmacologic properties and coupling mechanisms in nervous tissue, drugs that selectively affect subtypes of muscarinic receptors could enhance cortical cholinergic function and thereby ameliorate certain cognitive impairments in Alzheimer's disease. PMID- 1749292 TI - Childhood sinusitis. AB - Childhood sinusitis is difficult to diagnose. It is classified on the basis of duration of inflammation--acute or chronic--and cause of inflammation--infectious or noninfectious. Infectious sinusitis is often a result of obstruction of the osteomeatal complex. Inflammation in noninfectious sinusitis is similar to the inflammatory changes detected in respiratory mucosa of patients with asthma. Acute sinusitis is primarily an infectious process similar to a prolonged infection of the upper respiratory tract. Plain radiography has limited value for the diagnosis of acute sinusitis in children. The most effective treatment of acute sinusitis is administration of a beta-lactamase-resistant antibiotic. Chronic sinusitis may be infectious, noninfectious, or both. Coronal computed tomography of the sinuses and nasal endoscopy are the preferred methods for determining the presence of chronic sinusitis. When physicians prescribe therapy for chronic sinusitis, they need to consider whether the underlying cause is infectious, noninfectious, or both. Treatment of chronic infectious sinusitis is most effective when a beta-lactamase-resistant antibiotic is administered. Chronic noninfectious sinusitis may respond to topically intranasally applied corticosteroids. If medical treatment fails to resolve the disease within 3 months, surgical intervention may be necessary. Finally, although an association between asthma and sinusitis exists, a cause-and-effect relationship has not been established. PMID- 1749293 TI - Ludwik Rydygier--famous Polish surgeon. PMID- 1749294 TI - The fluoroquinolones. AB - The fluoroquinolone class of antibiotics promises to become as diverse and as important as beta-lactam agents. The fluoroquinolones inhibit bacterial DNA gyrase and are bactericidal. All fluoroquinolones have potent activity against most gram-negative bacteria; ciprofloxacin is the most active against Pseudomonas aeruginosa. Activity against gram-positive organisms is variable; methicillin resistant Staphylococcus aureus has acquired resistance to the fluoroquinolones at an alarming rate. Currently available quinolones do not have, but new quinolone agents likely will have, substantial activity against anaerobic bacteria. Some quinolones are also active against Mycobacterium, Chlamydia, and Mycoplasma organisms. All fluoroquinolones have excellent absorption after oral administration; however, this process can be impaired by the presence of aluminum or magnesium-containing antacids and by zinc, iron, or calcium supplements. Ciprofloxacin is also available for intravenous use. Although most fluoroquinolones do not achieve adequate cerebrospinal fluid levels, penetration into other tissues is excellent. Dosage adjustments for renal and hepatic dysfunction vary among the quinolones. Although side effects are rare, concomitant use of caffeine or theophylline with some quinolones may cause toxicity to the central nervous system. Because they may affect the development of cartilage, all fluoroquinolones are contraindicated in children, adolescents, and pregnant or breast-feeding women. PMID- 1749295 TI - Trimethoprim-sulfamethoxazole. AB - The antimicrobial combination of trimethoprim and sulfamethoxazole is active in vitro against various gram-positive and gram-negative bacteria. Clinically, it is useful for prophylaxis and treatment of selected infections of the genitourinary, respiratory, and gastrointestinal tracts. Trimethoprim-sulfamethoxazole by itself or in combination with other antimicrobial agents is indicated for most Nocardia asteroides infections and is the antimicrobial agent of choice for Pneumocystis carinii pneumonia. The drug is relatively nontoxic in patients who do not have the acquired immunodeficiency syndrome (AIDS) and is available in both oral and intravenous forms. The native compounds and the metabolites of trimethoprim and sulfamethoxazole are excreted primarily in the urine. When the creatinine clearance is less than 30 ml/min, the dosage of trimethoprim-sulfamethoxazole should be adjusted. PMID- 1749296 TI - Tetracyclines, chloramphenicol, erythromycin, clindamycin, and metronidazole. AB - The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and also can be used for gonococcal infections in patients unable to tolerate penicillin. These drugs may cause gastrointestinal irritation, diarrhea, phototoxic dermatitis, and vestibular damage, and fatal reactions due to hepatotoxicity have occurred in pregnant women. Chloramphenicol has a broad spectrum of bacteriostatic activity, but its association with suppression of the bone marrow and aplastic anemia has relegated it to a historical role. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious adverse effects associated with the use of erythromycin is low; dose-related epigastric distress may occur. Clindamycin is bactericidal to most nonenterococcal gram positive aerobic bacteria and many anaerobic microorganisms. Although historically it was a frequent cause of antibiotic-associated diarrhea and colitis, clindamycin is considered an excellent alternative to beta-lactam antibiotics for treatment of many staphylococcal infections, and it has therapeutic utility in anaerobic infections and in several protozoan infections in immunosuppressed patients. Metronidazole is efficacious for treating nonpulmonary anaerobic infections, various parasitic infections (trichomoniasis, amebiasis, and giardiasis), nonspecific vaginitis, and Clostridium difficile mediated colitis. With use of metronidazole, mild side effects such as epigastric discomfort, diarrhea, reversible neutropenia, and allergic-type cutaneous reactions may occur. PMID- 1749297 TI - Management of echinococcal cysts of the liver. PMID- 1749298 TI - Trends in cancer incidence, survival and mortality in northern Sweden 1960-1986. AB - The impact of cancer on a population may be measured in several ways. Incidence, relative survival and mortality are frequently utilized for this purpose. Incidence and relative survival are, however, often influenced by changes in the diagnostics of incident cancer, particularly by an altered rate of detection of non-fatal cancer. Mortality, as traditionally studied, is often influenced by changes of death causes diagnostics or of coding routines. In an attempt to overcome some of these difficulties, the concept of excess mortality was suggested, which is independent of death cause diagnoses or coding routines, as well as of the rate of detection of non-fatal cancer. In order to elucidate time trends in the overall effects of cancer we analysed incidence, survival and mortality from all cancer in the northern region of Sweden 1960-1986. An increasing age-adjusted cancer incidence was paralleled by an improvement in relative survival, whereas age-adjusted cancer mortality was mainly unchanged, at least when studied as excess mortality. We interpreted these findings as due mainly to an increased detection of non-fatal cancer, and to an unchanged occurrence rate of fatal cancer. PMID- 1749299 TI - Hemopoietic stem-cell differentiation in fetal liver, spleen and thymus of rhesus monkeys. PMID- 1749300 TI - Resistance of single tumor cells and their intracellular compartments to lipid peroxidation. AB - An attempt was made to analyze heterogeneity of tumor populations with respect to potential stability of single cells and their intracellular compartments (lipid containing refractory granules, RG, and cytoplasmic sites) to lipid peroxidation (LP). LP was initiated by a combined action of hypoxia and u.v.-light and measured by the level of fluorescent product of lipid peroxidation (FPLP) well distinguished from other fluorescent components of the cell. Irrespective of the cell growth stage, RG were found to make a major contribution to the total intensity of FPLP of the cell. However, this contribution was minimal (20 to 30%) in exponentially growing ascites tumor cells and maximal (70 to 90%) in the stationary growing ones. It is noteworthy that in both cases the heterogeneous tumor population has cells with a high stability to inhibitory and cytokilling action of LP. We believe that the approach suggested in this work is of potential importance for experimental and clinical practice since it is highly sensitive for detecting FPLP in single cells, which allows one to reveal various subcellular tumor populations and estimate their stability to LP. PMID- 1749301 TI - Interphase cell death as related to the cell cycle of melphalan-treated human myeloma cells. AB - The effect of melphalan on cell loss, cell growth and cell-cycle traverse was studied on the human myeloma cell line RPMI 8226. Melphalan treatment resulted in arrest of cells in late S- and G2-phases in a population of unsynchronized cells. At high concentrations of melphalan (e.g. 40 microM), cell loss was noticed during the first cell cycle after melphalan treatment in addition to the aforementioned arrest of cells in late S and G2. The cell loss after melphalan treatment was further analysed in cells enriched for G1-phase. Cell death in this population of cells occurred between 24 and 48 hr after treatment as the cells were in S and moving over to G2. PMID- 1749303 TI - 5-Fluorouracil (FU) and mitomycin C (MMC) in the management of colorectal carcinoma. Part II. In vitro activity of the two drugs in short-term tumor cultures. AB - Eighty-seven colorectal adenocarcinomas from untreated patients were investigated by short term tumor cultures to test in vitro sensitivity to 5-fluorouracil and mitomycin C. This study reports the preliminary results of a multistep program aimed at the prospective clinical application of the assay. At present this in vitro experience was performed in parallel with a clinical trial carried out with the same drugs. The in vitro activity of the two anticancer agents is in agreement with the response rate reported in monochemotherapy; our data would suggest an increase of responses using the combination of fluorouracil and mitomycin in comparison to single drug therapy. A low cosensitivity rate and a high number of cases sensitive to one drug but resistant to the other, account for the use of this test as screening of active drugs in the individual patient. PMID- 1749302 TI - 5-Fluorouracil (FU) with folinic acid (FA) and mitomycin C (MMC) in the adjuvant treatment of colorectal carcinoma. Part I. Evaluation of toxicity. AB - Ninety-six patients with colorectal cancer (stage B2-C) were randomized to the control arm or to receive adjuvant chemotherapy with folinic acid, FU and MMC. Ninety-three patients are evaluable. The median follow up is 12 months. The average time between surgery and the start of therapy is 28 days. Toxicity is evaluable in 36 of 41 treated patients. Four patients (10%) failed to complete the projected treatment due to toxicity. Toxicity observed in 208 courses of therapy was mostly gastrointestinal and hematological. No cases of treatment related death or cancer-associated hemolytic uremic syndrome (C-HUS) were reported. The average relative dose intensity (rDI) of the projected treatment was 82.6%. Our study is ongoing and further patients are required to achieve statistically significant results. PMID- 1749304 TI - Interaction between cytostatics and nutrients. AB - Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The presence of the tumor alone may lead to reduced intake of different nutrients and treatment modalities such as surgery, chemotherapy and radiation therapy may further exacerbate nutritional disturbances. Dietary manipulation in experimental systems has shown improvement of tumor response to cancer therapy. Drug pharmacokinetics has been shown to be altered by changes in nutritional delivery. This article reviews the present knowledge, from experimental and clinical standpoints, of the potential role of different nutritional factors on the specific cancer treatment. It is obvious that alteration of at least some dietary factors affect the outcome of different forms of cancer treatment. Indeed, although interest in the clinical significance of optimal dietary intake and supplementation during cancer therapy so far remain marginal, accumulating data indicate that this area deserves further research attention. PMID- 1749306 TI - Cranial irradiation and cerebrospinal fluid levels of 6-mercaptopurine in children with acute leukemia. AB - We measured 6-mercaptopurine levels in the cerebrospinal fluid and plasma of 15 children undergoing treatment for acute leukemia. Plasma and cerebrospinal fluid samples obtained by lumbar puncture were collected before, during, and after cranial irradiation in order to evaluate a possible change in blood-brain barrier permeability to orally administered 6-mercaptopurine. Considerable interpatient variability has been observed in both plasma and cerebrospinal fluid 6 mercaptopurine levels. No statistical differences in the 6-mercaptopurine cerebrospinal fluid levels under the three different conditions could be detected. Our data suggest that cranial irradiation does not significantly influence the cerebrospinal fluid levels. PMID- 1749305 TI - Inflammation amplifies the antitumor cytostasis by human peritoneal macrophages. AB - The effect of an inflammatory environment on the antitumor cytostatic ability of human macrophages was examined. Peritoneal macrophages of patients on continuous ambulatory peritoneal dialysis (CAPD) were collected, when CAPD was without complication, during an intercurrent infectious inflammation and after recovery. Inhibition of 3H-thymidine uptake served as a measure of cytostasis by macrophages co-cultured with target murine cells MOPC-315 plasmacytoma, WEHI-3B myelomonocytic leukemia and L929 transformed fibroblasts. Macrophages from inflammatory peritoneum expressed a markedly enhanced cytostasis, irrespective of the nature of the tumor cell. Endotoxin (LPS) challenge of inflammatory macrophages failed to further reinforce the cytostasis towards MOPC-315 plasmacytoma, but reinforced the cytostasis towards WEHI-3B leukemia (sensitive to inhibition by IL-1) and towards L929 (sensitive to TNF alpha). Cytostasis by supernatants of human peritoneal macrophages against L929 was markedly inhibited by anti-rHuTNF alpha and against WEHI-3B by anti-rHuIL-1 beta. The results suggest a link between inflammatory function and antitumor cytostasis by macrophages. This link is constituted by mediators involved in the activation process of macrophages. PMID- 1749307 TI - Methotrexate, vinblastine, epidoxorubicin and cisplatin (M-VEC) in patients with locally advanced transitional bladder cancer. AB - M-VEC (methotrexate, vinblastine, epidoxorubicin and cisplatin), a new combined drug regimen in which epidoxorubicin has been substituted to adriamycin to reduce the toxicity of the original M-VAC chemotherapy, has been tested in 23 patients with locally advanced transitional cell bladder cancer (TCBC) (stage T2-T4 No Mo). After two to four courses, an objective response was observed in 19 patients, with 13 clinical complete responses. Seven patients underwent cystectomy after chemotherapy: one patient had no residual tumor on bladder specimens, five patients had a surgical eradication of the disease, while one patient had only a partial resection. Eight relapses of bladder carcinoma were observed, three among the surgically treated patients and five among patients who did not undergo cystectomy, with a median time-to-relapse of 9.7 months. Progression-free survival at 24 months was 52.3%. M-VEC regimen appears to be effective in locally advanced TCBC, with acceptable toxicity. PMID- 1749308 TI - Temporal dynamics of pituitary prolactin depletion and release in three strains of rats. AB - Previous reports have shown that pituitary prolactin is rapidly transformed to a less soluble, but much more releasable, form prior to release from the lactotroph. One manifestation of this transformation is that pituitary prolactin depletion is significantly greater than concurrent release both in vivo and in vitro. The objective of this study was to compare the magnitude and temporal dynamics of depletion and release from pituitaries of ovariectomized estrogen treated rats of three different strains in vitro to assess the effect of strain on the transformation process. Mature ovariectomized Wistar-Furth (WF), Sprague Dawley (SD) and Long-Evans (LE) rats (7-10/group) were killed by decapitation 7 days after a single s.c. injection of 100 micrograms of polyestradiol phosphate. The anterior pituitaries were quickly removed and cut into quarters which were incubated for up to 4 hrs in the absence of dopamine or other prolactin secretagogues. Representative fragments from each strain were not incubated but were snap frozen to measure pre-incubation content. Fragments from each strain were removed from incubation at 30, 60, 120, 180 and 240 min for prolactin content measurement. Medium was collected at 30 min intervals and replaced with fresh medium. The experiments were repeated twice. Prolactin in medium and pituitary homogenates was measured by radioimmunoassays using NIAMDD-RP-1 as standard. In all three stains release of prolactin was approximately 30-50% of the prolactin depleted from the pituitary in 4 hrs. Strains varied in the magnitude of this difference and the time course over which it occurred. WF and SD rats showed significantly greater depletion and release of prolactin than did LE rats when the data were expressed as micrograms prolactin/mg pituitary. When the data were expressed as a percentage of prolactin available for release, the differences in depletion between strains disappeared and the LE rats released a significantly greater percentage of the prolactin available for release than did the other two strains. We conclude that pituitary prolactin undergoes a process of transformation prior to release which causes it to disappear from the pituitary but not appear in culture medium. We further conclude that the magnitude and temporal dynamics of this process are not equivalent across all strains of rats. PMID- 1749309 TI - Acute sodium-dependent changes in membrane dynamic properties. AB - Na+ ions, which can play a pathogenic role in the development of high blood pressure, have been reported to regulate membrane enzymatic activities, receptor ligand interaction and coupling of G-protein receptors to their effectors. This study was designed to investigate the in vitro effects of Na+ ions on membrane dynamic properties. The fluorescence anisotropy values of TMA-DPH (trimethylamino diphenylhexatriene, probe selectively incorporated into the outer leaflet of the plasma membrane) was evaluated in platelets and erythrocytes of sodium-dependent hypertension-prone and -resistant rats of the Sabra Strain. Whereas no difference was observed between the 2 strains, TMA-DPH anisotropy was found to be strongly influenced in platelets by external Na+ ions. In the absence of external Na+, TMA DPH anisotropy increased in human and rat platelets. In contrast, Na+ ions did not affect the anisotropy when the probe was inserted into erythrocyte ghosts. This indicates that Na+ ions can acutely regulate order parameter and microviscosity of platelet plasma membrane in the regions explored by the probe. PMID- 1749310 TI - Cytoskeleton-dependent release of human platelet epidermal growth factor. AB - To study the source of immunoreactive epidermal growth factor (ir-EGF) released by thrombin formation we removed 99.9% of the leukocytes normally present in platelet-rich plasma and induced coagulation with 30 mM of Ca2+. The absence of leukocytes did not reduce the amount of ir-EGF released; thus platelets are most likely the only source of the ir-EGF released during aggregation. To identify the site of ir-EGF in platelets we exposed washed platelets to collagen or thrombin and compared the kinetics of releases of ir-EGF, beta-thromboglobulin (bTG, an alfa-granule marker), ATP (dense granule marker), N-acetyl-beta-D-glucosaminidase (NAGA, a lysosome marker) and lactate dehydrogenase (LDH, a cytoplasmic marker). Release of ir-EGF started immediately and continued linearly. The process differed clearly from the releases of the granule markers, which occurred readily, and were completed in a few minutes. The release of ir-EGF also differed from the leakage of LDH, the start of which was delayed greater than 5 min, but then proceeded linearly. Cytochalasin B inhibited the release of hEGF, but demecolcine had no effect. We conclude that the ir-EGF released from platelets during aggregation derives neither from the granules nor the cytoplasma. The assembly of cytoskeleton is needed for its release. PMID- 1749311 TI - Toxicity of "DiI" for embryonic rat motoneurons and sensory neurons in vitro. AB - The carbocyanine dye DiIC18(3) ("DiI") is commonly used for both anterograde and retrograde labeling of neurons, including live neurons in situ and in vitro. In the present experiments, DiIC18(3) was used to label motoneurons in the spinal cords and sensory neurons in the dorsal root ganglia of embryonic rats. When the neurons from these regions were placed in culture, the neurons labeled by the dye were found to die rapidly, suggesting that DiIC18(3) can be toxic to neurons of these types. A related dye, DiIC12(3), was found to be equally suitable for labeling these neurons, and was found not to have detectable toxic effects in vitro. PMID- 1749312 TI - The mechanism of low susceptibility to stress in gastric lesions of spontaneously hypertensive rats. AB - The mechanism of low susceptibility to stress in gastric lesion formation in spontaneously hypertensive rats (SHR) was investigated focusing on the sympathetic and parasympathetic nervous systems. In the gastric tissues of SHR, norepinephrine (NE) and dopamine (DA) contents were higher, while acetylcholine content and choline acetyltransferase activity were lower than those of Wistar Kyoto rats (WKY). Water-immersion restraint induced gastric lesions frequently in WKY (ulcer indices : 52 +/- 7mm2) but less frequently in SHR (ulcer indices : 3 +/- 1mm2). Although NE content decreased in both SHR and WKY as a result of water immersion restraint, it remained higher in SHR than in WKY. ACh content decreased by the procedure in WKY but not in SHR. DA content was increased by the procedure in all gastric regions of SHR. The gastric lesions induced in SHR were aggravated by pretreatment with 6-hydroxydopamine, an agent for chemical sympathectomy, following decreases of NE and DA contents. These results indicate that the relative sympathetic hyperfunction, parasympathetic hypofunction and dopaminergic mechanism in the stomach contribute to the prevention of gastric lesion formation in SHR. PMID- 1749313 TI - Inhibition of proliferation of fibroblasts by lazaroids (21-aminosteroids). AB - Lazaroids (21-aminosteroids) are a novel group of compounds that inhibit lipid peroxidation in biological systems and protect cells from oxidative damage during tissue injury. In vivo efficacy of lazaroids has been demonstrated in a variety of animal models of traumatic or ischemic injury of central nervous system (1-6). However, very little is known about the affects of lazaroids on cellular responses associated with tissue repair and remodeling eg cell proliferation and synthesis of extracellular matrix. In the present study, we show that lazaroids and certain related compounds inhibit cell proliferation in vitro. Light microscopic examination and determination of release of intracellular enzyme, lactate dehydrogenase suggested that cell growth inhibition by lazaroids was not due to cell death resulting from cytotoxic effects. Examination of several lazaroid related antioxidants and other known antioxidants eg vitamin E and Probucol showed that compounds with similar antioxidant potential did not exhibit identical antiproliferative activity, suggesting that cell growth inhibition by lazaroids may be unrelated to their antioxidant action. These results may have implication in the therapeutic actions of lazaroids. PMID- 1749314 TI - Forging connections: the consumer connection. PMID- 1749316 TI - Restructured workplace could result in chaos. PMID- 1749315 TI - Parental assistance important in pain control for children. PMID- 1749317 TI - Sorting the complexities of respiratory distress syndrome. PMID- 1749318 TI - Giving infants and children drugs: precision + caution = safety. PMID- 1749319 TI - A crossword quiz: labor and delivery medications. PMID- 1749320 TI - Standards for testing and test users. PMID- 1749321 TI - "Rust v. Sullivan". PMID- 1749322 TI - Needle recapping: do we practice what we preach? PMID- 1749323 TI - Investigating "greedy.". PMID- 1749324 TI - [The capillary blood flow in the lungs of patients with chronic laryngeal and tracheal stenosis]. AB - Altogether 19 patients with chronic laryngo- and tracheostenosis of different etiology were investigated. All the patients were broken into 3 groups (1--less than 1 year, 2-1-3 years, 3--over 3 years) with regard to the time of canulla bearing. The patients were examined with 99mTc-human serum albumin particles. Major disorders in the capillary blood supply of both lungs were detected. These changes were focal-diffuse. Abnormalities were mainly observed in the apical area of both lungs and in the mediastinal zone. Redistribution of the pulmonary blood supply in the direction of the upper parts of the lungs was revealed. Lung abnormalities increased depending on the time of canulla bearing. PMID- 1749325 TI - [The ultrasonic diagnosis of changes in the hepatobiliary system in the practice of mass medical examinations]. AB - Investigation of 1258 servicemen during the first year of their service using ultrasound scanning of the hepatobiliary system has shown signs of chronic cholecystitis in 170, chronic hepatitis in 70, pyelonephritis and renal calculi in 120; 25 servicemen were recommended for further medical examination. It has been concluded that ultrasound scanning must become part of obligatory investigations of conscripts. PMID- 1749326 TI - [A case of the ultrasonic detection of familial autoimmune thyroiditis]. AB - During mass screening of 22,053 persons a case of familial autoimmune thyroiditis was detected by ultrasound investigation. Diagnosis was based on characteristic ultrasound signs of thyroiditis and was reaffirmed by cytological and immunological methods of investigation. PMID- 1749327 TI - [The radiation therapy of bladder cancer in a regimen of nontraditional fractionation with local radiomodification by metronidazole]. AB - The authors presented short-term and immediate results of radiation therapy of bladder cancer by a conventional method and optimized program, combining accelerated hyperfractionation and local radiomodification with metronidazole. A variant, proposed by the authors, included the use of a single focal dose of 1.4 Gy twice a day with a 4-hour interruption up to a total dose of 39.2 Gy. It was followed by a dose of 6 Gy once a week with preliminary administration of 2 g of metronidazole in 30-40 ml of 50 per cent dimexide solution in the bladder. A total of 2 large fractions of irradiation combined with metronidazole were used. This method was used for the treatment of 89 cancer patients. Better local control and survival in anemic patients with poorly differentiated cancer were observed. PMID- 1749328 TI - [The surgical treatment of radiation damage to the rectum]. AB - Radiation therapy of cervical cancer causes late radiation lesions of the rectum in a majority of patients. Surgery is a method of choice of the treatment of postradiation corrosive strictures and fistulas. Modern diagnosis of complications permits adequate surgical rehabilitation. PMID- 1749330 TI - [The structure of radiation therapy and of the guarantee of its quality]. PMID- 1749329 TI - [Physicotechnical and dosimetric support of human whole-body irradiation in a standard medical source of photon radiation]. AB - The paper is concerned with physicotechnical and dosimetric support of technology of therapeutic whole-body irradiation on a serial gamma apparatus ROKUS, with which a majority of radiological institutions in the USSR are fit out. Technology consists of the following procedures: patient positioning with relation to a source with a horizontal axis of radiation. Correction of dose distribution by means of a three-element compensator taking into account patient's constitutional peculiarities and preradiation preparation data; double irradiation in the bilateral regimen in the supine position. PMID- 1749331 TI - [Postmanipulation hemostasis in angiography from different approaches]. AB - The paper is concerned with some data on the quality of hemostasis after various types of angiography in 629 patients: manual hemostasis in transfemoral catheterization was used in 130 patients, mechanical fixing rubber pellets were used in 108 patients. Postmanipulation tamponade in the area of catheterization was used in 163 of 321 patients after catheterization translumbar angiography. In mechanical hemostasis, hematomas were found in 1.8%, in manual hemostasis--in 4.6%; CT and USI findings showed no hematomas after catheterizations translumbar angiography, in PTLA hematomas over 200 ml were found in 3.7%. PMID- 1749332 TI - [The characteristics of managing cancer patients during gamma teletherapy]. AB - Gamma-beam therapy of cancer patients is accompanied by general and local radiation reactions, their degree depending on numerous factors (a tumor site, an area of irradiated tissues and a value of a total absorbed dose). Preventive and therapeutic measures during radiotherapy allow the reduction of severity of a course of general and local radiation reactions. PMID- 1749333 TI - [The chronicle of Russian roentgenology: the first pages (1896)]. PMID- 1749334 TI - [The ultrasonic study of the liver, its large vessels and the spleen in chronic diffuse liver diseases]. AB - The paper is concerned with some methodological aspects of ultrasound investigation of the liver, portal veins and the spleen, the importance of this investigation for the detection, differential diagnosis and follow-up of patients with various chronic liver diseases. PMID- 1749335 TI - [The current achievements in radiopharmaceutical dosimetry]. PMID- 1749336 TI - Enemy radar, theoretical physics, and computer-assisted diagnosis. PMID- 1749337 TI - Analysis of complex data, image reconstruction, and Joshua Willard Gibbs. PMID- 1749338 TI - The HELP system: a review of clinical applications in infectious diseases and antibiotic use. AB - The HELP hospital information system, now under development for more than 20 years, has become an essential part of the daily operation of LDS Hospital, a 500 bed tertiary-care facility in Salt Lake City, Utah. The overall goal of the system is to provide decision-making capabilities for medical personnel and thus improve patient care. Since 1983, clinical applications have been available to improve the use of antibiotics and increase infection control. This article describes these applications and the essential features of the HELP system. PMID- 1749339 TI - A computer-based outpatient medical record for a teaching hospital. AB - We developed a computer-based outpatient medical record system to facilitate direct physician interaction with the clinical computing system at the Beth Israel Hospital in Boston. During the 2 years since the medical record system was installed, 20 staff physicians, 5 fellows, 64 residents, and 11 nurse practitioners have entered 15,121 active problems and 1996 inactive problems for 3524 patients, as well as 12,651 active medications and 1894 discontinued medications for 3430 patients. Another 20,321 items were entered on health promotion and disease-prevention screening sheets, and with the help of automatic updating by the computer, an additional 21,897 entries on screening sheets were made for 8686 patients. Clinicians wrote 10.9 +/- 12.8 (mean +/- SD) words per problem when they were working at the computer, as compared with 4.3 +/- 2.5 words per problem when they were writing in the paper medical record. We conclude that physicians will readily enter data directly into a computing system when they are given appropriate tools, and that they consider the computer-based problem list to be a valuable improvement over its paper counterpart. Use of a computer-based medical record system has obvious benefits for data management and patient care. PMID- 1749340 TI - Reasoning foundations of medical diagnosis. PMID- 1749342 TI - Getting to know your operating system. PMID- 1749341 TI - Obligations of the expert system builder: meeting the needs of the user. AB - Builders of expert systems have generally accepted the principle that computer software should not be subject to government regulation if health care practitioners can be expected to interpret and apply the systems intelligently. The purpose of this paper is to identify the information that builders must make available to permit health care practitioners to exercise their clinical judgment in interpreting and applying the output of computing systems. PMID- 1749343 TI - Medical hardware and software. Buyers guide. PMID- 1749344 TI - How to produce instructional text for a medical audience. AB - Instructional text continues to play a major role in medical education. Production of this type of learning resource requires an understanding of the objectives of the learner and the characteristics of text which facilitate student learning. Success in producing effective readable text requires attention to the content as well as to the way it is presented. This review outlines the factors which have a major impact on those two elements. PMID- 1749345 TI - Can medical education be researched? AB - Many medical educators are tempted or encouraged to conduct research into teaching techniques, methods of evaluation, and curricular change. These educators are generally career physicians who become distressed by their inability to apply the social science model of research to their project with impunity. This paper addresses the issues involved in conducting educational research and provides some suggestions for methodology that can be used. PMID- 1749347 TI - Teaching medical decision making and students' clinical problem solving skills. AB - Medical students need to be taught explicitly about decision making to be prepared for the changing health care environment. Medical decision making curricula have received favourable responses from students and have influenced some aspects of student performance. Questions remain about the impact of the teaching on students' general problem solving skills. A 15 hour course covering decision making topics was presented during a preclinical elective preceptorship for 5 years. Problem solving ratings made by clinical supervisors for the third year psychiatry and internal medicine clerkships were not better for the students who had the instruction and clinical experience than for the students in the comparison group. The results suggest that this approach to teaching decision making requires further development and testing. PMID- 1749346 TI - Alternative medical school curriculum design: the independent study program. AB - The University of Wisconsin Medical School established an alternative Independent Study Program (ISP) in the basic medical sciences in 1972. This program enabled class size to be increased without increasing laboratory teaching space, provided better education for students with diverse educational backgrounds, permitted individual progress, and promoted independent study. When compared to the most receptive oriented regular curriculum students (RCR) and those most discovery oriented (RCD), the preferred learning style of self-selected ISP students was more discovery or self-directed. They retained that style after graduation, while RCD students frequently became less discovery oriented. The ISP group was older, had more females, and had more advanced degrees. Although they had lower undergraduate grade point averages, they did well on the Verbal, General Information, Problem-Solving, and Quantitative sections of the MCAT. They also did well scholastically in Medical School, scored well on the National Boards Medical Examination, had the same distribution of residencies, and obtained the same quality of residency placement for medicine, surgery, and pediatrics. They have been very supportive of the program and feel that it was valuable in developing their abilities for continued self education. PMID- 1749348 TI - The way we train the clinical eye through slides. AB - Inspection is an important clinical skill. It is remarkable that in basic medical education this skill is not specially trained. To remedy this, we have developed a method of instruction at Groningen University Hospital to train inspection. We give an outline of the method and provide examples of dialogue. PMID- 1749349 TI - When babies die: death and the education of obstetrical residents. AB - This paper, based on 4 years in a Department of Obstetrics and Gynecology in which the author was both a resident physician and anthropologist participant observer, explores how obstetrical residents are taught to deal with the birth of anomalous and/or dead or dying babies. Not only is formal training lacking in this area, but residents may be strongly sanctioned for any emotional response in such situations. This paper argues that unless, and until, residents are taught to recognize and deal with, rather than repress, their responses, these physicians-in-training will not be equipped to help grieving parents deal with these situations. PMID- 1749350 TI - Medical education and the GCSE generation--a transferable activity-skills programme in medical sociology. AB - The first major intake of medical students who studied the new GCSE occurred in Autumn 1990. These students have experienced a range of student-centred educational approaches to learning, but medical education in the UK remains committed to teacher-centred approaches. This mismatch of expectations is discussed. An innovative course in medical sociology at the University of Sheffield is reported, which illustrates student-centred learning approaches including transferable activity-skills development and self-assessment profiling. An innovative approach to course evaluation is discussed. PMID- 1749351 TI - [The dual condemnation of Gramsci. A tentative biographical interpretation]. AB - This study proposes a "biographical" approach using a particular heuristic method. The structure of an important and significant letter written by Gramsci while in prison is analysed in this light. This interpretation leads us to the conclusion that, at the time of writing, Gramsci was in full possession of all his mental faculties, although worried by his long imprisonment and smitten by a profound disillusion as a result of the deformation of the "socialist" system. The victim of a "dual seclusion", he was not only able to make an exhaustive analysis of the situation, but in a certain sense he also succeeded in predicting the tragic events which were taking shape on the historical-political horizon of the world to which he belonged. PMID- 1749352 TI - [Clinical investigation on depression on a randomized and stratified sample in an elderly population]. AB - The prevalence of depression in the elderly was investigated in a random stratified sample of 100 subjects from the general population of Appignano (Macerata, Regione Marche, Italy). After sampling with the simple random method, each subject underwent a diagnostic work-up including: a) three psychodiagnostic tests (Short Scale for the Assessment of Mental Health--SSAMH, Geriatric Depression Scale--GDS, and Scale for the Self-evaluation of Depression from the Psychogeriatric Interview--PGI) and b) psychiatric evaluation (according to DSM III-R diagnostic criteria). Results were as follows: a) all the 3 tests (SSAMH, GDS, PGI) were suitable for the goals of this research, with a sensibility of 95.4%, 90.9%, and 95.4%, and a specificity of 90.4%, 88.9%, and 90.5%, respectively; b) the prevalence of depression in the sample was 25.9% (26.1% in females and 25.6% in males); c) the most common disorder was dysthymia, with higher percentage in females than in males (75% and 50% of all the depressive syndromes, respectively); d) the prevalence of depression was higher in females 60-69 years old and in males 70-79 years old. PMID- 1749353 TI - [Psychopathological heterogeneity in opium drug addicts]. AB - The aim of the study was to assess the presence and nature of psychiatric disorders in opium drug addicts. One hundred and six subjects receiving treatment at the CMAS in Cagliari were included in the study. Hathawai and McKinley's MMPI test was preventively carried out on all subjects; each drug addict was then interviewed three times in the space of three weeks in order to formulate a diagnosis in line with DSM III R criteria. The results obtained show a high incidence of psychopathological disorders which are not included among those caused by drug abuse, and a high degree of diagnostic heterogeneity on both axis I and axis II. The comparative assessment of three subsamples undergoing different phases of treatment reveals both qualitative and quantitative differences. PMID- 1749354 TI - [Custodianship or abandonment in psychiatry? The neo-contractual hypothesis]. AB - In this report role, possibilities and limits of psychiatry have been taken into account. Starting from a historical analysis, the Authors advance some hypotheses. Psychiatry could possible play a mediation role between sociology and biology, providing every patients with a specific therapy. PMID- 1749355 TI - [Dynamic psychopathology for a unified approach to psychogenic eating disorders]. AB - The paper focuses on psychopathological problems relating to psychogenic dietary disorders. Using a psychodynamic approach, the Authors hypothesise the existence of a structural "continuum" which links these diseases to the contexts of either exaggerated food consumption or reduced or insufficient food intake. The discussion in centered on the dynamic-genetic aspect, also taking into account intermediate psychopathological morphologies, which underlies this branch of clinical psychiatry. The failure to overcome "infantile dependence" is identified as the most important genetic factor. The type and efficacy of strategy used to neutralise the persistent anxiety caused by this unresolved "separation/identification" of the Ego shape the individual symptomatology of each dietary disorder described in the study. PMID- 1749356 TI - [Time in depression]. AB - Subjective estimation of time varies according to age, to physical state and to the activity we are occupied with. The relationship between time and major depression can be considered from two different point of view. From a clinical psychological point of view normal subjects with major depression estimate time intervals differently. Future, past and present change their meaning in major depression. These alterations cause important consequences in the cognitive structure of subjects with major depression and therefore influence depressive symptoms. On the other hand also the "biological time" is altered in major depression. Subjects with major depression suffer from many chronobiological alterations. The relationship between these two aspects are considered in the present report. PMID- 1749357 TI - [Acting out and schizoid personality]. AB - The Authors examine the crime-symptoms, sole index of an asymptomatic clinic history, and make some remarks on the indexes of social dangerousness. By this point of view, the structural traits of pre and post-critic personality seem to be a first predictory index. In relation to this question the Authors make mention to schizoidia. PMID- 1749358 TI - [Graphology in intuition, science and conscience. Cognitive possibility and ethical behavior of the graphologist]. PMID- 1749359 TI - Mental health and the community. PMID- 1749360 TI - Libel and medicine. PMID- 1749361 TI - The medical and legal trauma of disasters. PMID- 1749362 TI - Medical negligence: disclosure of risk and causation (Singapore). PMID- 1749363 TI - Drugs for sexually transmitted diseases. PMID- 1749364 TI - Rapid metabolic failure in spontaneously hypertensive rats after middle cerebral artery ligation. AB - The metabolic characteristics of the penumbral region were examined in spontaneously hypertensive rats one hour after permanent middle cerebral artery occlusion. The effect of hyperglycemia on this region was examined by providing a glucose load prior to occlusion. The depressed concentrations of adenosine triphosphate and elevated levels of lactate in the penumbral region were similar to those found in the ischemic focus. The purported neuroprotective effect of hyperglycemia in the penumbral region was not reflected in an increased high energy phosphate level in the penumbral region. The rapid deterioration of the metabolic status of this region in this strain of rat suggests that the increased consistency of infarction may come at the expense of the penumbral region, and thus this model may not be well suited for the study of metabolic changes and perhaps even therapeutic intervention. PMID- 1749365 TI - Cerebrospinal fluid amino acids in relation to neurological status in experimental portal-systemic encephalopathy. AB - Using an indwelling cisterna magna catheter technique, serial CSF samples were analyzed for amino acid content in rats at various stages of portal-systemic encephalopathy resulting from ammonium acetate administration following portacaval anastomosis. Anastomosis alone resulted in increased CSF concentrations of glutamine, tyrosine, phenylalanine, glutamate and alanine. GABA levels, on the other hand were not significantly changed. Onset of severe neurological symptoms following ammonium acetate administration resulted in selectively increased CSF alanine. Other amino acids were not further increased at severe stages of encephalopathy. Increased CSF alanine probably results from increased glutamine transamination in the brains of portacaval shunted rats. PMID- 1749366 TI - Transient changes in energy metabolites and intracellular pH during spreading depression in the chick retina. AB - The in vitro preparation of the chick retina can be used to show the occurrence of transient changes in the intracellular pH and of energy metabolites which occurs during spreading depression (SD). There is an initial increase in intracellular pH associated with elevated values for ADP, P-Creatine, lactate and pyruvate, an intermediary acid shift with increases in ATP values and decreases in ADP, and a late alkaline rebound where P-Creatine levels are reduced and the content of ADP and lactate are elevated. These transient changes in intracellular pH observed during SD, when correlated to the levels of energy metabolites, supports the hypothesis that the intracellular pH can be used by the tissue as a mechanism to rapidly modify the metabolic activities of neurons and glial cells. We suggest that the first alkaline shift is caused by glial cells and the intermediary acid shift by neurons. However, a specific cell could not be pointed out as responsible for the late alkaline shift but it could explain the refractoriness of the neurons during the phenomenon. PMID- 1749367 TI - Energy metabolism in rat hippocampus during and following seizure activity. AB - The hippocampus exhibits a post-ictal phenomenon in which it is unresponsive to further stimulation. It has been suggested that this loss of excitability is the basis of post-seizure amnesia. The biochemical events associated with this phenomenon are unclear. In the present study, energy metabolites were measured in the stratum oriens, stratum pyramidale and stratum radiatum in rat hippocampus, and correlated with field potential recordings. Wistar rats were anesthetized and the calvarium removed. Following removal of the cortex by aspiration, the hippocampus was covered with oil, and stimulating and recording electrodes were placed. Stimulation consisted of a train of stimuli at 100 Hz (10-20 m Amps). This stimulation was found to be effective in evoking self-sustaining after discharges and post-ictal depression. Tissues for metabolite analysis were taken from a series of controls, from animals during active self-sustaining seizures, and from animals which were totally unresponsive to further electrical stimulation. Hippocampal tissue for metabolite analysis was obtained by pouring liquid N2 on the exposed tissue, then removing the frozen tissue. Glucose, ATP, and phosphocreatine were measured in hippocampal layers of CA1 using fluorescence techniques and enzymatic cycling. Results showed that during seizure activity, glucose, ATP, and phosphocreatine were all decreased from 40-80% in the three layers of the hippocampus, whereas from 60 seconds after the onset of hippocampal shutdown, energy metabolites had returned toward normal. Thus, at a time when the hippocampus was unresponsive, energy metabolites were at control levels. These data suggest that the shutdown phenomenon occurs in the presence of adequate energy stores. PMID- 1749369 TI - Characteristics and risk behaviors of homeless black men seeking services from the Community Homeless Assistance Plan--Dade County, Florida, August 1991. AB - The number of homeless persons in the United States has been estimated to range from 600,000 to 3 million (Dr. Barbara Cohen, The Urban Institute, personal communication, 1991), with higher concentrations of these persons in several large urban centers. Because of the circumstances of homelessness, neither the health status nor the public health needs of these persons are well defined. In Dade County (which includes incorporated Miami), Florida (1990 population: 1.9 million), the average daily number of persons who are homeless is estimated to be 6000; during a 1-year period, approximately 10,000 persons are homeless at some time (Dr. Andrew Cherry, Barry University, Miami, personal communication, 1991). This report presents findings from a survey conducted in August 1991 to assess the health risks of homeless persons in Dade County seeking services from the Community Homeless Assistance Plan (CHAP), a pilot case-management project that places homeless persons into housing, jobs, and appropriate social services. PMID- 1749368 TI - Synergistic effect of bile acid, endotoxin, and ammonia on brain edema. AB - The effects of cytotoxic substances such as ammonia, bile acids and endotoxin, all of which increase in the circulating blood during fulminant hepatic failure (FHF), on the blood-brain barrier (BBB) permeability and development of brain edema were examined in the rats. Direct intracarotid injection of various bile acids resulted in the staining of the cerebral hemisphere with Evans blue as well as the increase of brain water contents. Elevation of ammonia was also observed in the cerebral hemisphere where the reversible opening of the BBB was induced by deoxycholate under hyperammonemic conditions. To see the synergistic significance of cytotoxic substances (ammonia, bile acid and endotoxin) under the more physiological condition as FHF, they were simultaneously injected into a peripheral vein. Brain uptake index of 14C-inulin and brain water content increased, and electron micrographs showed the swollen astrocytic foot processes surrounded brain capillary, but not opening of tight junction, the same as an animal model of fulminant hepatic failure. The results suggest that ammonia, bile acids and endotoxin might have a possible synergistic role in the pathogenesis of the brain edema, mainly cytotoxic, and vasogenic due to acceleration of vesicular transport, in FHF. PMID- 1749370 TI - Tuberculosis among residents of shelters for the homeless--Ohio, 1990. AB - During 1990, 17 cases of clinically active pulmonary tuberculosis (TB) occurred among residents of homeless shelters in three Ohio cities (Cincinnati, Columbus, and Toledo). This report summarizes the results of investigations of these cases by the Ohio Department of Health. PMID- 1749371 TI - Deaths among homeless persons--San Francisco, 1985-1990. AB - In San Francisco (1990 population: 723,959), an estimated 6000-18,000 persons are homeless. To characterize the causes of death among homeless persons in San Francisco during 1985-1990, the Health Care for the Homeless Program, San Francisco Department of Public Health, reviewed records of homeless decedents from the city medical examiner's (ME's) office. This report summarizes the results of that study. PMID- 1749372 TI - Federal regulatory action against sporicidin cold sterilizing solution. PMID- 1749373 TI - Food and Drug Administration approval of use of diphtheria and tetanus toxoids and acellular pertussis vaccine. PMID- 1749375 TI - Analysis of the structural relationships between the DNA-binding phosphoproteins pp42, pp43 and pp44 by in situ peptide mapping. AB - A structural homology is established between three DNA-binding phosphoproteins located in the 42 to 44 kDa range, referred to as pp42, pp43 and pp44, from Chironomus tentans salivary gland cells by in situ peptide mapping. The staining patterns of pp42, pp43 and pp44 which resulted from digestion with Staphylococcus aureus V8, trypsin or papain proteases show the presence of 8 to 15 spots majority of which have identical mobility. In the patterns of the digests generated by treatments with trypsin about 10 spots appear in common between any pair of the protein substrates. In addition, each pattern includes two to three peptides of mobility not present in the other. Thus the peptide mapping of pp42, pp43 and pp44 based on the staining patterns of proteolytic digests suggest the existence of structural homology between the three unlabelled substrates. The proteolytic peptides carrying the rapidly turning over phosphate groups form markedly different electrophoretic patterns than the unlabelled peptides visualized by staining. Treatment of 32P-labelled pp42, pp43 and pp44 with V8 generates only one labelled fragment in the 30 kD range. The cleavage patterns of pp44 produced by chymotrypsin or papain contain seven to ten labelled fragments while those of pp42 and pp43 contain only two. The 32P-labelled tryptic peptides of pp42, pp43 and pp44 exhibit a ladder pattern for each substrate which probably arise by a consecutive removal of 25 to 35 amino acid residues from the primary digestion products pp29, pp29.5 and pp30 by cleavage of four to five putative interdomain regions. The possibility that these three structurally related phosphoproteins belong to the category of transcription factors is discussed. PMID- 1749374 TI - The role of glycation in aging and diabetes mellitus. AB - One of the hypotheses trying to explain the process of aging is the idea of glycation of proteins. This reaction, also called the Maillard or browning reaction, may explain age-related symptoms such as cataract, atherosclerosis and modification of collagen-containing tissues. Diabetics, which possess elevated blood sugar levels, show signs of accelerated aging exposing similar complications. The Maillard reaction, which occurs on a large scale in vivo, may play a key role in the initiation of these symptoms. PMID- 1749376 TI - Plasmodium falciparum: recombinant baculoviruses direct the expression of circumsporozoite proteins in Spodoptera frugiperda cell cultures. AB - The DNA coding for the circumsporozoite protein (CPS) of Plasmodium falciparum has been cloned into the baculovirus expression vector pAcYM1 and expressed in Spodoptera frugiperda (Sf9) insect cells. Three DNA constructs have been made: the first one directs the synthesis of the complete CSP (aa 1-412), the second leads to the production of a species devoid of the anchor domain (aa 1-391) and the third one to a molecule lacking both signal and membrane anchor sequences (aa 18-391). All three recombinant CPS were produced at about 3 micrograms per 10(6) infected cells and were characterized in terms of immunoreactivity and apparent molecular weight. Analytical purification of the recombinant proteins was achieved by a combination of heat treatment, acidification, isoelectric focusing and ion exchange chromatography. The purified material, when injected into mice, generated only modest antibody responses, although antisera from immunized mice reacted with control CSP antigens carrying or not the major immunodominant repeat region. PMID- 1749377 TI - DNA-protein cross-linking in L1210 cells sensitive and resistant to cis diamminedichloroplatinum (II). AB - The role of restricted cellular accumulation of cis-diamminedichloroplatinum(II) (cis-DDP) and altered repair of DNA-Pt-protein cross-links in the mechanism of L1210 murine leukemia cell resistance was examined. An immunochemical method was used to analyze the formation and removal of DNA-Pt-protein complexes in L1210 cells sensitive and resistant to cis-DDP. The accumulation of Pt into the cells and the binding of Pt to the DNA was measured by atomic absorption spectroscopy. The results demonstrated that both decreased accumulation of the drug and the rate of DNA-Pt protein cross-link removal may be important factors in L1210 cell resistance to cis-DDP. PMID- 1749378 TI - Sequence analysis of the first intron of the bovine gamma s-crystallin gene. PMID- 1749379 TI - Commemorative issue for the 100th anniversary of the discovery of antibodies (1890-1990). PMID- 1749380 TI - [The mechanism of diphtheria immunity and tetanus immunity in animals. 1890]. PMID- 1749381 TI - Discovery of antitoxins and development of antibody preparations for clinical uses from 1890 to 1990. PMID- 1749382 TI - IgG galactosylation--its biological significance and pathology. PMID- 1749383 TI - Structure of antibodies and their complexes with antigens. PMID- 1749384 TI - Dynamic aspects of antibody structure. PMID- 1749385 TI - Engineering monoclonal antibodies to determine the structural requirements for complement activation and complement mediated lysis. PMID- 1749386 TI - Diversification of the IgG molecule by oligosaccharides. PMID- 1749387 TI - The minimal antigen-binding fragment of antibodies--Fv fragment. PMID- 1749388 TI - Autoantibodies and autoantigens: a conserved system that may shape a primary immunoglobulin gene pool. AB - Formation of certain autoantibodies is associated with a variety of autoimmune diseases, but the production of small amounts of autoantibodies also occurs in the normal immune system. Germline-encoded IgM antibodies that are autoreactive and bind to diverse antigen structures with low affinity are prominent in the primary antibody repertoire. Many IgG disease-related autoantibodies differ in structure and binding properties from these normally occurring IgM autoantibodies. The two sets may arise independently, but some properties, such as shared idiotypes, link some members of the two populations. Many autoantigen targets of both sets of autoantibodies are structurally conserved among species, as are certain features of the autoantibodies themselves. These elements, interacting before exposure of the system to foreign antigens, may constitute a conserved system that contributes to shaping and maintaining a primary immunoglobulin gene pool. PMID- 1749389 TI - Ultrastructure of asteroid bodies in sporotrichosis. AB - Ultrathin sections were prepared from a paraffin-embedded tissue specimen which had been obtained from a sporotrichosis patient and in which large numbers of asteroid bodies had been observed. Electronmicroscopic examination of the ultrastructure of the asteroid bodies revealed a central fungal cell with peripheral rays. These cells were almost structurally identical with fungal elements found elsewhere than in asteroid bodies; and in the rays, electron-dense granular substance was arranged in layers marked by fissures and material resembling remnants of destroyed host cells. The outermost layer was formed of a granular substance of rather low electron density, surrounded by adherent cell membrane fragments. These findings suggest that an asteroid body might be composed of crystalline products of disintegrated host cells deposited around a fungal cell. PMID- 1749390 TI - A rapid Candida albicans hyphal-form growth inhibition assay: determination of myelomonocytic-mediated antifungal activity. AB - An in vitro microassay for the measurement of Candida albicans hyphal-form growth inhibition by myelomonocytic cells is described. The assay is rapid, easy-to perform and objective. A Candida strain capable of in vitro dimorphic transition from yeast to hyphal form has been employed. The assay is based on the incorporation of 3H-glucose by the fungus, the effect being dependent upon the time of pulse, size of the inoculum and concentration of radiolabelled metabolite. In particular, C. albicans hyphal form, obtained by a 3 h incubation in vitro in the presence of 10% fetal calf serum, is co-incubated with the effector cells. A pulse with 3H-glucose in water is then performed and the radioactivity incorporated by the residual Candida is taken as an indication of hyphal growth. We found that polymorphonuclear cells, peritoneal macrophages and the cloned GG2EE macrophage cell line significantly inhibited hyphal growth, the effects being time and effector-to-target cell ratio dependent. PMID- 1749391 TI - Penetrating gastric ulcer as a cause of mixed bacterial and fungal pericarditis. AB - We describe a case of pneumopyopericarditis caused by a mixture of fungal and bacterial pathogens. This originated from a gastric ulcer (within a hiatus hernia) which had eroded into the pericardial sac. Further complications included the late discovery of the ulcer and asplenism. Similar cases have been reported, but to the best of the authors' knowledge, none with an actual mixture of the two pathogens. PMID- 1749392 TI - Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases. AB - Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA. PMID- 1749393 TI - Opsonizing activity of C-reactive protein in phagocytosis of Aspergillus fumigatus conidia by human neutrophils. AB - In complement-free neutrophil monolayer assays pathological levels of C-reactive protein (CRP) were found to promote greater phagocytosis of metabolically-active conidia of Aspergillus fumigatus than dormant spores. This suggests that metabolically-active conidia bind CRP which facilitates in vitro phagocytosis by human neutrophils. PMID- 1749394 TI - Study of the invasion of human hair in vitro by Aphanoascus spp. AB - The course of the destruction of human hair in vitro by three species of the genus Aphanoascus (A. keratinophilus, A. fulvescens and A. verrucosus) was studied with light microscopy, and transmission and scanning electron microscopy. The results obtained show that all the three species develop keratinolytic activity. A. fulvescens and A. verrucosus have similar sequences of degradation, invading the hair through the cuticula, but without the presence of specialized erosive organs. A. keratinophilus, however, shows a different way of invasion, and the keratinolytic activity was mainly located in the cortex and from that point on expanded to the cuticula. PMID- 1749395 TI - Ultrastructural aspects of the demolition of human hair in vitro by Chrysosporium tropicum Carmichael. AB - The pattern of invasion of human hair in vitro by a non-dermatophytic fungus, Chrysosporium tropicum, was studied by transmission and scanning electron microscopy. The components of the hair were attacked in sequence, depending on their level of keratinization, i.e. their content of cystine. In the cuticle, the sequence of digestion was as follows: intercellular material, cytoplasmic membrane, endocuticle, exocuticle, layer A, and a thinner layer below the inner cytoplasmic membrane of the cuticle cells. In the cortex, the order was: cementing material, plasmalemma, intermacrofibrillar material, microfibrils and matrix of the microfibrils. At the same time a different mode of attack was radial penetration of the various layers without regard to degree of keratinization. This occurred by means of perforating hyphae originating in the cuticle from structures similar to appressoria. With both modes of attack, the process showed all the characteristics of enzymatic digestion rather than physical breakdown. Ch. tropicum thus demonstrated important physiological parallels with dermatophytes in its demolition of hair in vitro. This could be of interest in predicting its ability to infect in vivo. PMID- 1749396 TI - Kinetic study of antifungal activity of amphotericin B, 5-fluorocytosine and ketoconazole against clinical yeast isolates using liquid-phase turbidimetry. AB - The fungal growth of clinical yeast isolates and of VW32 clone of Candida albicans were measured in vitro using a liquid-phase turbidimetric system (Bioscreen from Labsystems, France) in defined conditions. Cultures were performed in Shadomy's liquid medium and the fungal growth automatically evaluated every 10 minutes for 24 hours using various concentrations of drugs. The system made it possible to test 200 culture samples in one experiment. Yeast sensitivity to drugs was also measured by using our routine semi-automatic turbidimetric system. We observed that kinetic patterns of activity of each antifungal agent were typical. The in vitro tests showed that of 927 clinical yeast isolates 99.2% were sensitive to amphotericin B, 94.4% to 5-fluorocytosine and 69.7% to ketoconazole. PMID- 1749397 TI - The preservation of fungal cultures by lyophilization. AB - A method for the preservation of fungal strains is presented. The cultures are grown on Sabouraud glucose agar in glass ampoules and lyophilized without further processing. By this method the macroscopical morphology of the cultures is preserved, so that these can be used immediately without recultivation as reference cultures. All tested mould and yeast strains remained viable over the six months duration of the experiment, whereas the dermatophyte strains could only partially be recultivated. PMID- 1749398 TI - Modification of responses of Candida albicans to cisplatin by membrane damaging antimycotic agents. AB - The genotoxic, antineoplastic platinum coordination complex, cisplatin (cis diamminedichloroplatinum (II], exists as a positively charged aquated complex in water solution and as a neutral, nonaquated complex in saline solution. Candida albicans exhibited greater susceptibilities to cellular inactivation and induction of mitotic recombination when treated with the aquated rather than the nonaquated drug. The differential in responses was expressed by cells grown after treatment at 37 degrees C or at 25 degrees C, a temperature which promotes recovery from DNA damages by the yeast generally. Studies with protoplasts established that cell wall components do not influence cellular reactions to either form of the drug. However, membrane damaging antimycotic agents markedly affected responses. Pretreatments with fungistatic ketoconazole or with miconazole, under fungistatic or fungicidal conditions, enhanced cellular resistance to inactivation by aquated cisplatin: the effect was more pronounced with post-cisplatin growth at 25 degrees C than 37 degrees C. Fungicidal pretreatments with amphotericin B or miconazole greatly increased susceptibilities of surviving cells to the lethal and recombinagenic effects of nonaquated cisplatin with post-cisplatin recovery at 25 degrees C or 37 degrees C. Possible mechanisms underlying these responses and their implications for stability of C. albicans populations in cancer patients undergoing therapy with cisplatin are discussed. PMID- 1749399 TI - Dermatophytoses in Cusco (Peru). AB - A total of 90 cases of suspected dermatophytoses was observed over a period of 9 months in the city of Cusco (Peru) and in its environs. The age groups most commonly infected were 1-10 and 11-20 year old. The most common tineae diagnosed were tinea capitis (13.3%) and tinea unguium (11.1%). Only four species of dermatophytes were isolated: Microsporum canis (52.4%), Trichophyton mentagrophytes (35.7%), Tr. rubrum (9.5%) and Epidermophyton floccosum (2.4%). Dry weather, low temperature and high altitude do not seem to affect proliferation and infections by dermatophytes. PMID- 1749400 TI - Effect of the incubation conditions on the production of patulin by Penicillium griseofulvum isolated from wheat. AB - Sixty-four wheat samples from Spanish flour factories were screened for patulin and patulin-producing moulds. None of them was found to contain any patulin, whereas samples experimentally contaminated with this toxin proved it to be highly unstable. On the other hand, Penicillium griseofulvum was the only in vitro patulin-producing species found (19 samples). Mould growth in the samples was investigated by using yeast-sucrose medium (YES) and high-performance liquid chromatography (HPLC) to measure the amounts of toxin produced during 40 day's incubation at 20 and 28 degrees C. The highest yield rate of patulin was obtained between the 20th and 30th day of incubation; such a rate, however, was very low throughout the vigorous growth phase, during the first 20 days of incubation. The more appropriate temperature for incubation and patulin production was 28 degrees C. We also investigated the influence of other incubation conditions in the yield and found stationary dark cultures to be more efficient that shaken or fermentation cultures in YES medium. The best patulin yield achieved was 11.9 mg in the culture broth and 6.3 mg in the mycelium from 100 ml of medium. PMID- 1749401 TI - Isolation of beauvericin as an insect toxin from Fusarium semitectum and Fusarium moniliforme var. subglutinans. AB - Nonpolar methylene chloride-soluble extracts from the mycelia of Fusarium semitectum and Fusarium moniliforme var. subglutinans were toxic to Colorado potato beetles. The major toxic metabolite was isolated and found to be the cyclodepsipeptide, beauvericin. This is the first report of the isolation of beauvericin from the genus Fusarium. PMID- 1749402 TI - Allergic contact dermatitis caused by mushrooms. A case report and literature review. AB - The first author is allergic to skin contact with mushrooms of Suillus americanus, S. granulatus, S. grevillei, S. luteus, or S. neoalbidipes. Symptoms develop between one and two days after contact and last for approximately a week, disappearing completely without treatment. Symptoms consist of reddening, swelling, and itching, at the sites of contact with pileus cuticle mucilage of all five species. Pore layer tissues (tested for S. americanus and S. luteus) also produced strong reactions, as did pileus trama (tested for S. luteus). Spores from spore prints (tested for S. americanus and S. luteus) produced no reaction. The reaction can be avoided by wearing gloves when handling allergic species and by washing hands promptly after working with these species. Similar cases, reported from North America, Europe, and Russia, involve Agaricus, Boletus, Lactarius, Paxillus, Ramaria, and Suillus species. Several cases involve allergy to multiple species or genera. Symptom severity varies, presumably with intensity of exposure. In one case, symptoms were renewed following ingestion. Most cases demonstrate delayed allergic contact sensitivity. PMID- 1749403 TI - Adhesion of Candida albicans to epithelial cells effect of polyoxin D. AB - Data from our previous studies suggested that the fungal cell wall component, chitin, is involved in the adhesion of Candida albicans to mucosal surfaces. In the present study, we investigated the effect of polyoxin D, an inhibitor of chitin synthase, on the interaction of the fungus with epithelial cells. The effect of polyoxin D on Candida was evaluated in in vitro assays for its capacity to adhere to buccal epithelial cells (BEC), and by fluorescent-microscopy photometry and flow cytometry using cells stained with cellufluor (CF), a fluorochrome with affinity for chitin. C. albicans grown with and without polyoxin D was stained with CF and examined in a fluorescent microscope equipped with a photometer. Measurements of fluorescence revealed a wide range of intensity among C. albicans cells and a decreased intensity in polyoxin D treated cultures. Flow cytometry analyses of yeasts revealed 2 peaks of fluorescence intensity, and pointed to differences between polyoxin D treated and non-treated microorganisms. C. albicans stained with CF were separated into 2 subpopulations by flow cytometry according to fluorescence intensity. In vitro adhesion of each subpopulation to BEC was similar. Polyoxin D treated fungi showed significantly reduced adherence to BEC, as evaluated by a radioactivity assay with radiolabelled yeasts and by microscopic readings. The reduction in adhesion was Polyoxin D concentration dependent. These observations support our previous findings suggesting involvement of chitin in the attachment process of C. albicans (CBS562) to epithelial cells. PMID- 1749404 TI - Cardiovascular toxicity of cocaine: underlying mechanisms. PMID- 1749405 TI - Cocaine-induced myocardial depression. PMID- 1749406 TI - Prevalence of myocardial ischemia in cocaine addicts. AB - The finding that most young cocaine addict patients had a negative exercise treadmill test suggests that they did not have preexisting obstructive coronary artery disease. Noninvasive testing did show, however, that these patients frequently had a high incidence of ST elevation episodes during the first 2 weeks of withdrawal. The pathophysiological mechanism of cocaine-induced cardiovascular disease is not yet clearly understood, but it is probably more complex than the drug's acute direct effects on the cardiovascular system. It may be complicated by fluctuations in catecholamine homeostasis and further temporally complicated by cycles of cocaine use and withdrawal. Research on how cocaine use alters catecholamine homeostasis will increase the understanding of the pathophysiology of cocaine and assist in developing effective pharmacologic and prophylactic treatment for its abuse. PMID- 1749407 TI - Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations. AB - Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha mediated, other in vitro data suggest the opposite. The finding of cocaine induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded. PMID- 1749408 TI - Cardiac electrophysiological effects of cocaine in animal models. PMID- 1749409 TI - Effects of cocaine on intracellular calcium handling in cardiac and vascular smooth muscle. AB - The inotropic and lusitropic (i.e., relaxant) actions of cocaine on the heart appear to be caused primarily by changes in intracellular calcium handling. The positive inotropic and lusitropic effects of low and moderate concentrations (i.e., less than or equal to 10(-5)M) are mediated by catecholamines; the negative inotropic effects of higher concentrations appear to be due to the direct local anesthetic effects of cocaine on excitation-contraction coupling mechanisms. The relevance of these findings to humans is suggested by the fact that blood levels of cocaine in excess of 10(-5) M have been described in patients abusing this drug (Van Dyke et al. 1976; Paly et al. 1982). Blood vessels from certain vascular beds, including the epicardial coronary arteries of humans and swine, show little or no constrictor response to low concentrations of cocaine and relax at higher concentrations. In contrast to the effects on the heart, the relaxant effects of cocaine on vascular smooth muscle appear to be related to marked changes in myofilament calcium responsiveness, which may be mediated by the protein kinase-C system. These results at least indicate that the depressant effects of cocaine on cardiac vs. vascular smooth muscle occur by different mechanisms and suggest the need for specific therapeutic approaches to managing cardiac depression vs. vasodilatation when they occur in cocaine intoxicated individuals. Moreover, these data provide evidence supporting the hypothesis that the net effects of cocaine in the intact organism are highly dependent on the underlying level of sympathetic adrenergic activity. PMID- 1749410 TI - Cocaine-induced changes in the biochemistry and morphology of rabbit aorta. PMID- 1749411 TI - Effects of cocaine on the physiology of exercise. PMID- 1749412 TI - Effect of acute cocaine administration on cardiac and respiratory patterning in the freely moving cat. PMID- 1749413 TI - Direct and indirect morphological markers of cocaine toxicity in the human heart. PMID- 1749414 TI - Cocaine-associated cardiovascular disease: clinical and pathological aspects. AB - With regard to cardiac findings in cocaine abuse, at autopsy the vast majority of patients dying with cocaine toxicity have either no pathologic change in the heart or only minimal changes that could not account for the patient's death. The second most frequent finding is underlying, mild-to-moderate coronary atherosclerosis, with or without coronary thrombosis. There may be acute or healed myocardial infarction or a sudden cardiac death without myocardial changes of ischemia. A high incidence of contraction band necrosis has been reported in the absence of coronary artery disease and may cause a sudden arrhythmic death. Myocarditis also has been described in a few cases as either lymphocytic or lymphocytic and eosinophilic infiltrate in the presence of myocyte necrosis. Usually, the foci are sparse and not always associated with contraction band necrosis. The underlying mechanisms are thought to be either direct effects of norepinephrine on myocytes or through vasospasm of resistance vessels and secondary myocardial ischemia. Cocaine rarely has been associated with aortic dissection, which is probably a result of cocaine's hypertensive effects. PMID- 1749415 TI - Pharmacokinetics and time-action profile of cocaine in dogs. PMID- 1749416 TI - Acute tolerance to the chronotropic effect of cocaine in humans. PMID- 1749417 TI - Mechanisms of cardiac and vascular responses to cocaine. PMID- 1749418 TI - Maternal-fetal cardiovascular system: a target of cocaine. PMID- 1749419 TI - Cardiovascular effects of cocaine in squirrel monkeys. PMID- 1749420 TI - Role of the sympathetic nervous system in the cardiovascular effects of cocaine. PMID- 1749421 TI - FDA vs. free speech over drug promotions. PMID- 1749422 TI - US plans frontiers support. PMID- 1749423 TI - HIV infection. France will compensate. PMID- 1749424 TI - Human genome dispute. PMID- 1749425 TI - Tissue shortage. PMID- 1749426 TI - Gene therapy on the move. PMID- 1749427 TI - A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. AB - The group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000. We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q, close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP. Another adRP gene has been mapped to chromosome 8p. A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p, showing tight linkage with the gene for peripherin, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmembrane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa. PMID- 1749428 TI - A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. AB - The human X-linked gene A1S9 complements a temperature-sensitive cell-cycle mutation in mouse L cells, and encodes the ubiquitin-activating enzyme E1. The gene has been reported to escape X-chromosome inactivation, but there is some conflicting evidence. We have isolated part of the mouse A1s9 gene, mapped it to the proximal portion of the X chromosome and shown that it undergoes normal X inactivation. We also detected two copies of the gene on the short arm of the mouse Y chromosome (A1s9Y-1 and A1s9Y-2). The functional A1s9Y gene (A1s9Y-1) is expressed in testis and is lost in the deletion mutant Sxrb. Therefore A1s9Y-1 is a candidate for the spermatogenesis gene, Spy, which maps to this region. A1s9X is similar to the Zfx gene in undergoing X-inactivation, yet having homologous sequences on the short arm of the Y chromosome, which are expressed in the testis. These Y-linked genes may form part of a coregulated group of genes which function during spermatogenesis. PMID- 1749429 TI - Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. AB - Recent advances indicate a link between tumour promoters, transformation, and AP 1 activity. Protein kinase C activation increases AP-1 DNA-binding activity independently of new protein synthesis. AP-1 is also stimulated by transforming oncoproteins and growth factors. These proteins are thought to participate in a signalling cascade affecting the nuclear AP-1 complex composed of the Jun and Fos proteins. Because c-Jun is the most potent transactivator in the AP-1 complex and is elevated in Ha-ras-transformed cells, in which c-Fos is downregulated, we focused on it as a potential target. c-Jun could convert input from an oncogenic signalling cascade into changes in gene expression. Indeed, transformation of rat embryo fibroblasts by c-Jun requires an intact transcriptional activation domain and cooperation with oncogenic Ha-ras. Expression of oncogenic Ha-ras augments transactivation by c-Jun and stimulates its phosphorylation. Here we describe the mapping of the Ha-ras-responsive phosphorylation sites to serines 63 and 73 of c Jun. Site-directed mutagenesis indicates that phosphorylation of these serines is essential for stimulation of c-Jun activity and for cooperation with Ha-ras in ocogenic transformation. PMID- 1749430 TI - [Paralysis of the recurrent nerve and a normal thorax picture: idiopathic?]. PMID- 1749431 TI - [Transient ischemic attacks, non-invalidating brain infarcts and the prevention of worse: current findings on its treatment]. PMID- 1749432 TI - [Serological diagnosis in rheumatoid arthritis]. PMID- 1749433 TI - [The surgical treatment of rheumatoid arthritis]. PMID- 1749434 TI - [Consensus cerebrovascular accident]. AB - A consensus conference on stroke was held on March 22, 1991. Subjects on which consensus was reached were: There are different kinds of cerebral haemorrhage and infarction, which can be differentiated by computerized tomography, and this can have practical consequences. At clinical examination special attention should be paid to cognitive impairment. Angiography is indicated only if carotid surgery or unusual causes are considered. CSF examination and EEG are performed only on special indications. Cardiological consultation is necessary in young patients, or if clinical signs of cardiogenic embolism are present. Coumarin derivatives are prescribed in some of these cardiac causes of stroke, to prevent recurrence. There is as yet no effective medical treatment for cerebral infarction. In lobar and cerebellar haemorrhage surgical treatment may be indicated. In the acute phase of stroke it is always important to prevent aspiration pneumonia, pulmonary embolism and decubitus, and to care for muscles and joints. Advantages and disadvantages of gastric tube and indwelling catheter should be weighed. Treatment of hypertension after the acute phase is indicated to prevent recurrent stroke. After TIA and minor stroke, aspirin is prescribed, which reduces the risk of cerebral and myocardial infarction by 30%. Carotid endarterectomy in symptomatic patients with carotid stenosis of 70% or more, reduces the number of fatal or disabling strokes by 50%, if perioperative complications are less than 4%. Rehabilitation after stroke reduces disability and improves the adaptation of both the patient and his environment. The patient should be stimulated and supported; good information, including the family, is essential. Supplying aids and taking special measures should be done on individual basis, after a period of training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749435 TI - [Prevalence of Lyme borreliosis in The Netherlands]. AB - In the autumn of 1989 a seroepidemiological study was carried out among 440 owners of hunting dogs and 1052 blood donors from different regions in the Netherlands. To detect IgG antibodies to Borrelia burgdorferi an enzyme-linked immunosorbent assay was performed. The prevalence of antibodies to B. burgdorferi in owners of hunting dogs was 15%, which was significantly higher than in blood donors (9%). In both groups the prevalence of seropositivity increased with age. There was no difference between men and women. The prevalence of antibodies to B. burgdorferi in blood donors from different regions varied significantly, ranging from 2% to 17%. Only 3% of the owners of hunting dogs could recall having had symptoms most likely to be due to Lyme borreliosis. Of the 68 seropositive hunters 64 (94%) were asymptomatic. The results of this study indicate that in the Netherlands asymptomatic infections with B. burgdorferi are common in individuals highly exposed to ticks and that there is considerable variation in the prevalence of seropositivity in the general population. Hence caution is called for in the clinical interpretation of IgG test results. PMID- 1749436 TI - [Exercise-dependent anaphylaxis]. AB - The clinical features of exercise-induced anaphylaxis in 5 patients are described, with an accurate history, skin tests, IgE determinations and exercise tests. In these 5 patients we were able to distinguish three different forms of exercise-induced disease: exercise-induced anaphylaxis based upon an IgE-mediated allergy to foods, exercise-induced anaphylaxis without food allergy and cholinergic urticaria. PMID- 1749437 TI - [How toxic is dioxin for humans?]. PMID- 1749438 TI - [Pancreatitis in children]. PMID- 1749440 TI - [Cell biology from a medical perspective. VIII. The cytoskeleton, cell movement]. PMID- 1749439 TI - [Identical breathing sounds]. PMID- 1749441 TI - [Hormonal aspects and hormone therapy of cancer]. PMID- 1749443 TI - [Report by the Commission Nomenclature Lung Sounds]. PMID- 1749442 TI - [Nephrotic syndrome: therapeutic possibilities]. PMID- 1749444 TI - [Comparison of iodine scintigraphy and computerized tomography in the localization of pheochromocytoma]. AB - A comparison is made of the results of CT scanning and MIBG scintigraphy in the localization of phaeochromocytoma. In 21 out of 24 patients with clinically diagnosed phaeochromocytoma in the University Medical Hospital, Groningen in 1983 1990, MIBG scintigraphy provided accurate localization, while in 16 out of 18 patients with phaeochromocytoma who underwent CT scanning a correct localization was obtained. False negative results were mainly present when lesions were smaller than 2 cm. There were no false positive results. It is concluded that the sensitivity of the two methods in the localization of phaeochromocytoma is about equal. The use of one of the methods rather than of both is advised. PMID- 1749445 TI - [Regulation of diabetes and late complications in the ambulatory treatment of patients with Type II diabetes mellitus]. AB - In order to obtain more information on the quality of metabolic control and presence of secondary complications in type 2 diabetic patients treated in a hospital outpatient-clinic, we studied 124 of our diabetic patients (56 males, 68 females, age 65 (SD 11) years, duration of diabetes 9, range 1-32 years). HbA1c levels were 7.9% in patients on oral hypoglycaemic agents (n = 56), and 8.2% in insulin-treated patients (n = 59). Cholesterol and triglyceride levels tended to be lower in the insulin-treated patients. The prevalence of vascular abnormalities was high: in comparison with a population of general practice patients more patients had hypertension (56% vs 38%), coronary artery disease (48% vs 40%), and cerebrovascular disease (15% vs 6%). In addition, 35% of our diabetics had signs of peripheral artery disease. Retinopathy was present in 35 patients, microalbuminuria was found in 31 patients, proteinuria in 18 patients. The presence of microalbuminuria and proteinuria was a strong indicator for cardiovascular disease, polyneuropathy and retinopathy. The use of cardiovascular medication was high: 57 patients used antihypertensive therapy, 37 used diuretics, and 26 long-acting nitrates. Only 25 patients took no medication apart from to their diabetes therapy. PMID- 1749446 TI - [Hemorrhagic fever caused by dengue in 2 tourists]. AB - Dengue haemorrhagic fever in two female tourists to Thailand (1990) and Indonesia (1989) respectively, is reported for the first time in the Netherlands. The main symptoms directly after return were high fever, haemorrhagic exanthema, thrombocytopenia and in one patient signs of haemoconcentration. Initially both patients were treated with antibiotics. They recovered after intravenous fluid therapy; one of them received a thrombocyte transfusion. Increasing travel to Asia and South America will result in more tourists returning with this potentially serious arboviral disease (dengue haemorrhagic shock). PMID- 1749447 TI - [Medical activities under adverse conditions. The Royal Institute for the Tropics]. PMID- 1749448 TI - [Are there still indications for plasma transfusions?]. PMID- 1749449 TI - [Cell biology from a medical perspective. IV. Cell nucleus and the action of the genome]. PMID- 1749450 TI - [Neurogenetics--the challenge for neurology. Part 1. Gene mapping and gene diagnostics]. AB - Recent advances in gene mapping have provided distinct chromosomal locations for a number of neurological disease genes. Mapping strategies include the identification of chromosomal aberrations associated with disorders and the candidate gene approach which requires correct assumptions about the primary biochemical defect. The most successful strategy, linkage analysis, relies on family studies and allows the mapping of genes without knowledge of the molecular cause of a disorder. Once the chromosomal position for a disease gene is known, indirect DNA diagnosis becomes available, providing risk estimates for individuals in affected families. Identification of the disease gene itself allows the characterization of the protein involved and direct diagnosis at DNA and protein level, thus leading to a greater understanding of the molecular pathology of neurogenetic disorders. PMID- 1749451 TI - [Neurogenetics--the challenge for neurology. 1. Neurogenetic diseases]. AB - Progress in molecular genetics has provided insight into a number of neurogenetic disorders. The chromosomal location of the genes for Huntington's disease, Wilson's disease, myotonic dystrophy and Friedreich's ataxia are now known. In families affected by these illnesses, linkage analysis can now be employed for presymptomatic or prenatal diagnosis. The genes for Duchenne and Becker muscular dystrophy and neurofibromatosis I have been cloned and sequenced, allowing the direct analysis of the genetic defect in many cases, and thereby providing further insight into the pathophysiology. In addition, the classification of several neurogenetic diseases, such as the hereditary motor and sensory neuropathies or the spinal muscular atrophies can now be based on the chromosomal location of the affected gene(s). PMID- 1749452 TI - [Anticerebellar antibodies--anti-Hu and anti-Yo--in the diagnosis of paraneoplastic neurologic syndromes]. AB - The detection of antineuronal antibodies against cytoplasm and nuclei of Purkinje cells is considered to be an essential factor in the diagnosis of neurologic paraneoplastic syndromes. Published data rely on different immunological methods and relatively small numbers of patients. The clinical relevance of this phenomenon is not clear from the literature. A positive correlation between antibody detection and the appearance of neurologic paraneoplastic syndromes has been reported, but this finding has been questioned in critical reviews. PMID- 1749453 TI - [Corpus callosum agenesis. Interhemispheric integration of semantic information]. PMID- 1749454 TI - [Speech apraxia in dialysis-associated aluminum encephalopathy]. AB - A 57-year-old man on long-term renal dialysis presented with speech dyspraxia, a symptom characteristic of early aluminium encephalopathy. Once fully developed, this condition has a poor prognosis despite deferoxamine (DFO) treatment. PMID- 1749455 TI - [Presenile dementia in xeroderma pigmentosum]. AB - Neurological manifestations of xeroderma pigmentosum, a rare autosomal recessive neurocutaneous syndrome, are variable. The association with progressive mental retardation, usually with onset in childhood, is well known. We present a case of x.p. with progressive presenile dementia. This combination has, to our knowledge, not yet been reported in the literature. Although no hints on another aetiology have been found, the coincidental combination of x.p. with M. Alzheimer has to be taken into consideration. CT scan and MRI showed a marked cerebral atrophy. PMID- 1749456 TI - [Clinical aspects and electrophysiologic findings in an unusual course of central pontine myelinolysis]. PMID- 1749458 TI - Effect of medial zona incerta lesions on the ovulatory surge of gonadotrophins and prolactin in the rat. AB - Bilateral electrolytic lesions of the incertohypothalamic A13 dopamine (DA) system were made on the morning of proestrus in female rats with regular estrous cycles under ether anesthesia. Hourly blood samples were withdrawn, via a jugular catheter from conscious, freely moving rats, between 14.00 h and 18.00 h on the afternoon of proestrus. Plasma LH, FSH and prolactin levels were determined by RIA. The preovulatory surges of LH and prolactin were blocked in animals in which the A13 DA nucleus was destroyed by more than 70%. Levels of FSH were not significantly different from those of control of sham-lesioned groups. Lesions that were dorsal, ventral or caudal to the A13 DA systems did not affect the preovulatory surges of LH and prolactin whereas anterior lesions caused variable changes in the level of all three hormones. These data suggest that the A13 DA region may have a role in the control of the preovulatory surges of LH and prolactin. PMID- 1749457 TI - Regulation of hypothalamic gonadotropin-releasing hormone and neuropeptide Y concentrations by progesterone and corticosteroids in immature rats: correlation with luteinizing hormone and follicle-stimulating hormone release. AB - In a previous study, we demonstrated that progesterone (P4) and the synthetic glucocorticoid triamcinolone acetonide (TA), but not cortisol, could induce LH and FSH release in estrogen-primed ovariectomized immature rats. Therefore, the purpose of this study was to determine if the stimulatory effect of P4 and TA on LH and FSH release were associated with changes in GnRH or NPY concentrations in the medial basal hypothalamus (MBH) or preoptic area (POA). Ovariectomized immature rats primed with estradiol at 27 and 28 days received either vehicle, P4, TA or cortisol (1 mg/kg BW) at 9.00 h on day 29. Animals were killed at 9.30, 10.00, 12.00 and 13.00 h on day 29 for serum LH and FSH measurements, and the MBH and POA were dissected and analyzed for GnRH and NPY concentrations via RIAs. P4- and TA-treated animals showed significantly elevated serum LH and FSH levels from 13.00 h to 15.00 h. Cortisol was without effect. P4 significantly increased MBH GnRH and NPY concentrations at 12.00 h followed by a significant fall at 13.00 h. P4 modulated POA GnRH and NPY concentrations in a fashion similar to that seen in the MBH, except POA NPY concentrations did not fall at 13.00 h after the elevation at 12.00 h. TA had no significant effect on MBH GnRH and NPY levels at 12.00 h compared to the values at 9.30 h and 10.00 h but, as with P4, there was a significant fall in MBH GnRH and NPY levels at 13.00 h. TA had no significant effect on POA GnRH and NPY concentrations at any time point studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749459 TI - Naltrexone does not reverse the inhibitory effect of chronic restraint on gonadotropin secretion in the intact male rat. AB - There is considerable evidence suggesting that endogenous opioids may play an important role in acute stress-induced decreases in luteinizing hormone (LH) release. Studies were undertaken to analyze the role of endogenous opioids in chronic stress-induced decrease in circulating LH and follicle-stimulating hormone (FSH). Chronic restraint (6 h daily over 4 days) evoked a decrease in circulating LH and FSH. Naltrexone treatment, (2 mg/kg three times daily) during the 4 days of restraint, caused an increase in plasma concentrations of LH and FSH, and antagonized the LH suppressory effect of morphine (10 mg/kg) administration. Despite this, naltrexone treatment was ineffective in preventing the inhibitory effect of chronic restraint stress on circulating LH and FSH. Chronic restraint also induced a decrease in hypothalamic LH-releasing hormone (LHRH) content in saline-treated rats. On the contrary, in naltrexone-treated rats, chronic restraint evoked an increase in hypothalamic LHRH content. Thus endogenous opioids and chronic stress seem to act by different mechanisms on the hypothalamic LHRH neuron. In unstressed orchidectomized rats, naltrexone administration did not modify circulating LH, but increased plasma concentrations of LH in acutely restrained rats. These data suggest that endogenous opioids may mediate gonadotropin secretion during acute stress, but not during chronic stress. PMID- 1749460 TI - Autoradiographic analyses of the effects of restraint-induced stress on 5-HT1A, 5 HT1C and 5-HT2 receptors in the dorsal hippocampus of male and female rats. AB - Quantitative autoradiography was used to evaluate the effects of sex and either 1 or 5 daily 2-hour sessions of restraint stress on binding at 5-HT1A, 5-HT1C and 5 HT2 receptors in the rat dorsal hippocampus. Neither sex nor restraint stress were found to have effects on binding at 5-HT1C or 5-HT2 receptors. However, restraint stress increased binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin at 5-HT1A receptors in the CA4 region and in the infrapyramidal dentate gyrus. In addition, levels of binding at 5-HT1A receptors in the oriens and lacunosum moleculare layers of the CA1 region were significantly higher in female rats. Neither estradiol benzoate nor estradiol benzoate plus progesterone had effects on binding at hippocampal 5-HT1A receptors in ovariectomized rats, making it unlikely that the sex differences were related to stages of the estrous cycle. Stress-induced levels of corticosterone (CORT) were higher in females. Although CORT levels in blood obtained during restraint decreased from session 1 to session 5 in both male and female rats, the decrease became significant in females only. Female rats also displayed higher levels of activity in the open field. Although activity in the open field was reduced in male and female rats after restraint, these decreases were not significant. Results are discussed in relation to anxiety and depression. PMID- 1749461 TI - Influence of human corticotropin-releasing hormone and adrenocorticotropin upon spontaneous growth hormone secretion. AB - Hormones of the hypothalamo-pituitary-adrenocortical (HPA-) axis are considered to be of physiological and clinical relevance in regulating spontaneous growth hormone (GH) secretion. To further investigate interdependencies between both systems, we studied the effects of adrenocorticotropin [ACTH(1-24)] and human corticotropin-releasing hormone (h-CRH) upon spontaneous GH secretion in 10 male volunteers. Administration of 1 microgram ACTH (1-24), 10 micrograms h-CRH or saline (control: CTL) every hour from 9.00 to 6.00 p.m. resulted in significant differences of cortisol secretion during the entire observation period (8.00 a.m. 3.00 a.m.) between the three groups (p less than 0.001, Friedman two-way ANOVA). Mean area under the time course curve (AUC) values (+/- SEM) for cortisol expressed as ng x 1,000 x min/ml showed also significant differences between the three treatments from 8.00 a.m. to 3.00 a.m.: CTL 64.0 +/- 6.4, ACTH(1-24) 178.5 +/- 9.4 (p less than 0.01, Wilcoxon test), h-CRH 88.5 +/- 5.6 (p less than 0.01). The main portion of cortisol was released during daytime from 8.00 a.m. to 11.00 p.m., where the most significant differences in the AUC values emerged: CTL 59.6 +/- 5.8, ACTH(1-24) 171.5 +/- 8.8 (p less than 0.01, Wilcoxon test), h-CRH 80.2 +/- 5.1 (p less than 0.01). With regard to GH secretion, significant differences became obvious between the three treatments during daytime from 8.00 a.m. to 11.00 p.m. and the sleep-related period from 11.00 p.m. to 3.00 a.m. (p less than 0.01 and p less than 0.02, Friedman two-way ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749462 TI - Effect of cold exposure on the hypothalamic release of thyrotropin-releasing hormone and catecholamines. AB - The effects of cold exposure on the release of thyrotropin-releasing hormone (TRH) and catecholamines as estimated by push-pull perfusion of the mediobasal hypothalamus were studied. Before cold exposure, the male rats had been kept at room temperature or at 30 degrees C for 3 weeks. Transfer to 4 degrees C increased plasma levels of thyroid-stimulating hormone (TSH), but this cold induced TSH response was more pronounced in animals which had been acclimatized to 30 degrees C. Exposure to 4 degrees C also increased plasma thyroid hormone levels, but had no effect on plasma prolactin. The hypothalamic content of TRH and dopamine remained similar after transfer to 4 degrees C, but after 6 h of cold, the content of noradrenaline and adrenaline had increased 1.6-fold and 3 fold, respectively. In vivo hypothalamic release of TRH, adrenaline and dopamine remained similar during a 2-hour period in control rats kept at room temperature or 30 degrees C. The hypothalamic release of TRH, dopamine and adrenaline did not change in rats transferred from room temperature to 4 degrees C. The amount of dopamine and adrenaline in push-pull perfusate also remained similar in rats acclimatized to 30 degrees C after transfer to low temperatures. However, in these rats kept at 30 degrees C for 3 weeks, exposure to 4 degrees C increased TRH release in perfusate from the mediobasal hypothalamus in the first 15 min of cold exposure (2-fold increase). Thus, exposure to cold stimulates the hypothalamo-pituitary-thyroid axis and increases the hypothalamic release of TRH in rats which had been acclimatized to 30 degrees C. PMID- 1749463 TI - Influence of pentobarbital and urethane on release from magnocellular neurons. AB - We examined the responses of vasopressin-neurons (VP-neurons) and oxytocin neurons (OT-neurons) to acute salt-loading in a group of conscious rats (CON, n = 8) and rats under sodium pentobarbital (NEM, 50 mg/kg, i.p., n = 8) or urethane (URE, 1.6 g/kg, i.p. n = 8) anesthesia. Fifteen minutes following the induction of anesthesia, sodium pentobarbital produced an increase in basal plasma osmolality (Posm, 290 +/- 2 to 296 +/- 3 mosm/kg H2O, p less than 0.007) while urethane did not change basal Posm (287 +/- 2 to 289 +/- 2 mosm/kg H2O). Neither anesthetic agent resulted in any significant changes in basal plasma levels of vasopressin-associated neurophysin (VP-RNP) and oxytocin-associated neurophysin (OT-RNP). In response to intravenous infusion of 18% saline, all three groups of rats had similar rises in Posm. The slopes of the relationship between the rise in plasma VP-RNP and the rise in Posm were markedly reduced in both groups of anesthetized animals compared to that observed for conscious animals (CON = 2.54 +/- 0.5; NEM = 1.22 +/- 0.18; URE = 1.17 +/- 0.24 fmol.ml-1.mosm-1.kg H2O-1 p less than 0.0126). The slopes of the relationship between the rise in plasma OT RNP and the rise in Posm were not significantly (p less than 0.4478) different between the CON group and the NEM group, while the slope for the URE group was significantly (p less than 0.05) smaller than that for the CON group (CON = 10.9 +/- 1.5; NEM = 9.3 +/- 1.5; URE = 6.3 +/- 0.7 fmol.ml-1.mosm-1.kg H2O 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749464 TI - Electrophysiological actions of oxytocin on hypothalamic neurons in vitro: neuropharmacological characterization and effects of ovarian steroids. AB - Oxytocin (OT) neurotransmission in the brain has a facilitatory effect on sexual receptivity in rats. This effect of OT is dependent on priming by ovarian steroids, estrogen and progesterone. These steroids modulate OT binding in specific brain nuclei, including the ventrolateral portion of the ventromedial hypothalamic nucleus (vlVMN). In the present study, single-unit activity was recorded from the vlVMN in hypothalamic slices to characterize the electrophysiological actions of OT. To examine the effects of ovarian steroids on OT actions, we used brain slices prepared from ovariectomized rats either treated with estrogen or not, and some slices were treated with progesterone in vitro. OT had little modulatory action on neuronal responses to other agents, but affected the activity of large numbers of vlVMN units. Of those neurons affected, 94% responded with excitation. This predominant stimulatory action of OT is consistent with its lordosis-facilitating effect, because increases in the activity of VMN neurons are generally associated with the facilitation of lordosis. Pharmacological analyses with selective OT agonists and antagonists as well as structurally related peptides showed that the excitatory action of OT is mediated by OT receptors. Estradiol modulated several aspects of OT transmission. First, it increased neuronal responsiveness to OT, especially at the lowest concentration used (0.2 nM). In addition, it caused neuronal responses to OT to correlate significantly with responses to acetylcholine and norepinephrine, which also can act on the ventromedial hypothalamus to facilitate lordosis. Finally, estradiol enhanced the excitability of laterally projecting neurons, which have been implicated in lordosis. In estrogen-pretreated slices, addition of progesterone in vitro caused little further effect on responses of individual neurons to exogenous OT. Altogether, the present electrophysiological findings are consistent with the hypothesis that estrogen potentiates OT action by increasing functional OT receptors preferentially in lordosis-relevant neurons, thereby enabling OT to efficiently facilitate female reproductive behavior. PMID- 1749465 TI - The role of imaging in the management of cerebral and ocular ischaemia. AB - The last decade has seen several major technological advances in vascular neuroradiology, the most clinically significant of which have been the facility to image the brain and the extracranial carotid bifurcation noninvasively with accuracy and safety. Another major advance has been unequivocal evidence from formal statistical overviews that antiplatelet therapy, particularly aspirin, reduces the risk of serious vascular events by about 25%. These advances have changed clinical practice such that most patients presenting with symptoms suggestive of cerebral ischaemia should now have cranial CT to exclude intracerebral hemorrhage, not only because the causes and prognosis of cerebral ischaemia differ from those of intracerebral hemorrhage, but because many patients with cerebral ischaemia should be considered for antiplatelet therapy. Besides the use of long term antiplatelet therapy and control of vascular risk factors, other acute treatment options are limited with the possible exception of anticoagulation, thrombolysis, cytoprotective agents and carotid endarterectomy. If, as seems likely, the current clinical trials show that carotid endarterectomy plus medical therapy improve upon the stroke-free survival of patients treated medically, at least in symptomatic patients with severe stenosis, the number of carotid endarterectomies performed will increase considerably because carotid bifurcation disease is the most common cause of cerebral and ocular ischemic events. It will then be even more important to be able to obtain accurate anatomical and physiological information about the extracranial and intracranial circulations with utmost safety. Duplex ultrasound is currently the noninvasive screening method of choice for carotid bifurcation disease because it is available, relatively cheap, and reasonably accurate. It not only images the vessel lumen and degree of stenosis, but also the morphology of the vessel wall and associated plaque, the relevance of which is still uncertain in the pathogenesis of cerebral and ocular ischaemia. A major limitation of duplex sonography is that it cannot reliably distinguish tight stenosis from occlusion and it does not image the proximal or distal carotid circulation. The aim of newer techniques will be to distinguish tight extracranial carotid stenosis from occlusion and to provide anatomical, physiological and pathological information about the intracranial circulation and ischemic lesions (in view of potential for thrombolytic therapy of major intracranial vessel occlusion) with safety and reproducible accuracy. PMID- 1749466 TI - MR imaging of the brainstem: normal postnatal development. AB - Magnetic resonance imaging (MRI) of the mesencephalon during the first four years of life allowed normal maturational processes of the various midbrain structures in vivo to be followed. Using T2-weighted SE sequences, we found 5 characteristic age dependent patterns on axial tomograms taken at the level of the superior colliculi, that let us derive a grading system for normal development of the quadrigeminal plate, the cerebral peduncles, the reticular substantia nigra and the red nuclei. A subsequent statistical analysis of these age dependent changing patterns on T2-weighted MRI of 60 neonates, infants and small children yielded normal age ranges for each of the 5 maturational stages of the midbrain. Grading the changing pattern of midbrain structures during early postnatal life into 5 distinct maturational stages allowed not only monitoring of normal differentiation, e.g. myelination of the brainstem in vivo, but may also help to distinguish between normal, delayed and abnormal development of the mesencephalon on routine MRI. PMID- 1749467 TI - MRI: a method to detect minor brain damage following coronary bypass surgery? AB - In order to assess the occurrence of minor focal brain lesions after coronary bypass surgery, magnetic resonance imaging (MRI) was used. Nine male patients (age 42-63) with angina pectoris were investigated at 0.5 Tesla. The investigation was performed one to seven weeks prior to the operation and one month after the operation. Before surgery, the images demonstrated more than five high intensity spots in the white matter of the brain in all but two patients. No additional spots were found after operation. This pilot study indicates that it might be difficult to use MRI to detect minor parenchymal lesions after cardiopulmonary bypass surgery. PMID- 1749468 TI - Granular cell tumour of the orbit: radiological findings. AB - Radiological findings in four cases of intraorbital granular cell tumour are presented, and compared with those previously reported. These rare lesions often appear to involve an extraocular muscle, and are seen on CT as an enhancing mass, usually well defined, and frequently lying anteriorly. Plain films are characteristically normal; angiographic findings range from normality to a dense tumour blush. PMID- 1749469 TI - Low-dose CT and inflammatory disease of the paranasal sinuses. AB - Computed tomography (CT) is the gold standard for exact delineation of inflammatory sinus disease, especially before endoscopic surgical treatment, and in cases of postoperative recurrences. In routine CT studies, the radiation dose to the patient is not negligible. Therefore, the authors evaluated prospectively the CT scans of 44 patients with inflammatory disease of the paranasal sinuses, to define the imaging ability of low-dose CT (i.e. 60 mA-3 s, 30 mA-3 s, and 30 mA-2 s), comparatively with the standard mAs settings (130 mA-3 s). In all cases, the exact extent of the disease was correctly assessed on each of the low-dose settings, with no false negative study. The increasing graininess of low mAs sections did not induce errors of interpretation, despite a less pleasant appearance to the eyes. In cases of extensive sinus disease, the thickness and integrity of the ethmoid septa were sometimes more difficult to evaluate on low dose CT sections. The authors recommend the use of low mAs settings in the evaluation of inflammatory disease of the sinuses, complemented, if necessary, in cases of extensive abnormalities, by one or two sections obtained with standard mAs settings, focused on questionably abnormal bone septa. PMID- 1749470 TI - Lumbar percutaneous discectomy. Initial experience in 28 cases. AB - Since November 1988, 28 patients with lumbar L5 radiculopathy refractory to conservative care and with a radiologically verified central or mediolateral disc herniation at the level of L4/L5 had had a percutaneous discectomy. Radiological verification consisted of spinal CT +/- myelography, +/- myelo-CT, +/- MRI. A short-term follow-up analysis of at least 2 months taking the clinical and functional status as well as the professional reintegration into account revealed a 64.3% (18/28 patients) satisfactory outcome and a 32.1% (10/28 patients) failure rate. Of the latter 28.6% (8/28 patients) required further open surgery. One patient whose pain had only partially in regressed was shown at open operation to have a sequestered cranial prolapse as revealed by spinal CT after the percutaneous procedure. There were no major complications. One patient developed a sequestered extraforaminal herniation through the nucleotomy canal three weeks after the procedure. One patient bled for 2 minutes. There were no major vessel injuries. One patient reported local muscular pain, and enhanced nerve root pain after introduction of the trocar sleeve. PMID- 1749471 TI - Theory and practice: how much contrast for myelography? AB - A questionnaire sent to members of the British Society of Neuroradiologists revealed that the majority of practitioners will, when necessary, inject more than 3 g of iodine during myelography with iohexol or iopamidol. The 3 g limit recommended by the contrast medium manufacturers is not based upon scientific studies involving these media, and it is the experience of British neuroradiologists that larger amounts of modern contrast agents can be used without an increase in post myelography complications. There is, therefore, a need for a controlled trial to assess the question of the most appropriate dose of contrast medium in myelography. PMID- 1749472 TI - CT of adult lumbar disc herniations mimicking posterior apophyseal ring fractures. AB - This report concerns 35 adult patients with lumbar or sciatic pain and axial CT findings reportedly associated with posterior apophyseal ring fractures. Review of the CT images suggested two pathophysiologic categories. (1) Posterior Schmorl -A posterior intravertebral disc herniation with posterior displacement of a fractured or remodelled vertebral margin. (2) Calcified subligamentous--Reactive annular and or posterior longitudinal ligament calcification at the periphery of a herniated disc with or without remodelling and anterior displacement of the posterior vertebral margin. PMID- 1749473 TI - Combined use of spin-echo and gradient-echo MR-imaging in cervical disk disease. Comparison with myelography and intraoperative findings. AB - In a prospective study we compared the diagnostic value of combined gradient-echo (GE) and spin-echo (SE) MR imaging with cervical myelography in 30 patients with clinical signs and symptoms of cervical radiculopathy and/or myelopathy due to disk disease. Only patients who subsequently underwent surgery (anterior interbody approach) were included. By means of MRI the clinically relevant segment was identified in all cases, by means of myelography in all but two patients. Using both spin-echo (SE) and gradient-echo (GE) techniques it was possible to differentiate between bone tissue and disk material by MR in all but one. It is concluded that MRI-especially gradient-echo imaging is a viable alternative to cervical myelography and can be considered as an initial diagnostic procedure for suspected cervical disk disease. PMID- 1749474 TI - Long term follow-up of diffuse idiopathic skeletal hyperostosis in the cervical spine. Analysis of progression of ossification. AB - In eleven patients with diffuse idiopathic skeletal hyperostosis who presented with extensive ossification in the cervical spine, progression or regression of ossification during the follow-up period were measured in extent and thickness radiographically. Intervertebral range of motion was also measured and the relation between changes of ossification and intervertebral mobility was analyzed. The range of motion at the segments at which ossification progressed was statistically quite different from those at which no progression was observed. It was found that ossification grew in thickness at mobile segments and no growth of ossification was present at immobile segments. Dysphagia caused by massive ossification was cured by surgical removal in two cases. Recurrent ossifications were detected in them some years after surgery, and one of them complained of dysphagia again. To prevent recurrent ossification and dysphagia, it was considered that immobilization of the concerned segment was necessary by bone grafting or preservation of the continuity of ossification. PMID- 1749475 TI - Visual toxicity following intra-arterial chemotherapy with hydroxyethyl-CNU in patients with malignant gliomas. A prospective study with statistical analysis. AB - We studied the effects of intra-arterial chemotherapy (IAC) with a new nitrosourea (hydroxyethyl-chloroethyl nitrosourea: HeCNU) on the visual system of 68 patients with malignant gliomas. The intra-arterial chemotherapy was given as a complementary treatment of glioma after surgery (19 patients), after tumor recurrence (28 patients) and as the preliminary treatment before radiotherapy (21 patients). Eleven patients (16%) suffered a visual complication after two or more courses of chemotherapy. The main visual symptoms included mild to major decrease of visual acuity and in some cases ocular pain, palpebral edema and conjunctival injection. The delay in onset of ocular symptoms from the last course of IAC varied from 1 week to 9 months. From ophthalmoscopic findings, visual field testing and fluorescein angiography, the visual symptoms presented by our patients could be related to ischemic optic neuropathy or retinal vasculopathy. None of the patients had hypertension, diabetes, cardiopathy or hematological disease. Statistical analysis failed to demonstrate a relationship between the occurrence of visual toxicity and patient age, number of courses of HeCNU, the vascular axis treated, total systemic dose or dose by carotid artery, suggesting a possible specific sensitivity of some patients to chemotherapy. The pathophysiology and the therapeutic implications of this visual toxicity are discussed. PMID- 1749476 TI - Computed tomography in Alexander's disease. An atypical case with extensive low density in both frontal lobes. PMID- 1749477 TI - Hajdu-Cheney syndrome: MR imaging. AB - Hajdu-Cheney syndrome is a rare congenital disease with acro-osteolysis, osteoporotic changes of the spine and long bones of extremities and marked basilar invagination with an unusually deformed skull. Magnetic resonance imaging of a 32-year-old male revealed the deformed skull and almost horizontal basal angle and the elongated and upwardly shifted brain stem caused by the tip of the odontoid process of the second cervical vertebra invaginating the base of the skull. In addition there were atrophic pituitary gland, widely open sella turcica and symmetrical fluid collections along the optic nerve sheath. PMID- 1749478 TI - Gd-DTPA-enhanced MR imaging of cryptococcal meningoencephalitis. AB - This report describes magnetic resonance (MR) imaging of biopsy-proved cryptococcal central nervous system (CNS) infection in a 31-year-old HIV negative man. Initial MR imaging revealed multi-focal Gd-DTPA enhancement and showed more lesions than contrast enhanced CT. The lesions regressed after antifungal therapy. MR imaging aids in diagnosis as well as helps to monitor the response to the pharmacological therapy of cryptococcal meningoencephalitis and possibly provides valuable insights into the pathophysiology of this condition. PMID- 1749479 TI - Medulloblastoma with extensive calcification. AB - Calcification in cases of medulloblastoma has been described with varying frequency (10%-15.4%) on computed tomographic (CT) scan. Usually these calcifications are small in size and speckled. The authors report a case of medulloblastoma with extensive calcification in the lateral hemisphere of the cerebellum in an 18-year-old boy. PMID- 1749480 TI - Massive ischemic cerebellar infarction due to cocaine use. AB - This young female suffered massive unilateral infarction of the cerebellum due to cocaine use. While cocaine-associated small, asymptomatic cerebellar infarcts have been reported in the literature, massive, symptomatic cerebellar infarction attending the use of cocaine has not been previously reported. PMID- 1749481 TI - Aneurysm of the lingual artery. Endovascular treatment. PMID- 1749482 TI - Bony exostosis of the atlas with resultant cranial nerve palsy. AB - A case of tenth and twelfth nerve compression secondary to a bony exostosis of the first cervical vertebra is described. This uncommon phenomenon serves to outline the importance of imaging the course of a cranial nerve when no intracranial abnormality is demonstrable on CT or MRI. The radiologic features of spinal osteochondromas are reviewed. PMID- 1749483 TI - MRI diagnosis of thoracic ossification of posterior longitudinal ligament with concomitant disc herniation. AB - Ossification of the posterior longitudinal ligament is a potentially curable cause of thoracic myelopathy. As this case illustrates, MRI can confirm the diagnosis, demonstrate other concomitant pathology such as disc herniation, and help assess the clinical significance of OPLL by showing spinal word compression. PMID- 1749484 TI - Capillary hemangioma in the cauda equina: neuroradiological findings. AB - A case of capillary hemangioma of the cauda equina is reported. Myelography with water-soluble contrast material showed a complete obstruction of the contrast column at the L1-L2 level. Neither plain nor intravenously enhanced CT revealed the tumor. Spinal angiography showed a feeding vessel to the tumor and a faint tumor stain. Magnetic resonance imaging (MRI) showed a mass lesion of slightly higher than cauda equina intensity, which was clearly enhanced with Gd-DTPA. MRI, especially Gd-DTPA-enhanced study, plays the most important role in the diagnosis of a spinal capillary hemangioma. Spinal angiography was interesting in showing a tumour with a capillary blush. PMID- 1749485 TI - Spinal epidural cavernous angioma. MRI finding. PMID- 1749486 TI - Posterior dislocation of the neural arch of L5 due to spondylolysis. PMID- 1749487 TI - Agenesis of a lumbar pedicle: MR demonstration. PMID- 1749488 TI - CT and MR of the sellar spine. PMID- 1749489 TI - Cerebral berry aneurysms and systemic lupus erythematosus. PMID- 1749490 TI - Snakebite management. PMID- 1749491 TI - Ballistics accuracy. PMID- 1749492 TI - Physical training. PMID- 1749493 TI - A philosophy of limb salvage in war: use of the fixateur externe. AB - Over the period 1973-1983, we treated by external fixation 110 severe grade three open or complicated fractures caused in war (minimum follow-up, 7 years). We present our data analyzed according to method, location, and type of fracture. The methods we have evolved over the years are described in detail: primary wound stabilization by fixateur externe; primary radical wound excision, repeated every 48 hours as required, including excision of dead bone; delayed primary vascular soft tissue cover; delayed primary or secondary skeletal and soft tissue reconstruction as dictated by local wound conditions; prophylactic antibiotics and intensive physiotherapy to the joints and muscles of the injured limb and as rapid an ambulation of the patient as possible. The advantages and limitations of external fixation are enumerated. It is possible to avoid the complications of pin tract infection and ring necroses, but care is required to avoid refracture after removal of the apparatus, since the quality of bone healing is not always good with the use of external fixation. External fixation has greatly facilitated the various methods for achieving delayed primary vascular soft tissue cover over severe open fractures, bringing about an improved prognosis; micro-vascular techniques hold great promise for wound cover and skeletal reconstruction. Similarly, the Ilizarov method of bone osteotaxis has opened up new vistas in the treatment of bone mass loss. The latter requires a sophisticated set-up which will not be available in most war zones. In spite of the advances in treatment and in the improved results achieved by modern techniques of wound stabilization, wound soft tissue cover, and bone and soft tissue reconstructions, the temptation to try to salvage useless limbs must be resisted. Amputation, judiciously adjudged and correctly timed, remains one of the most successful forms of treatment in these severe injuries, saving the casualty from a physical and spiritual via dolorosa. Enthusiasm for surgical endeavor must be well tempered with mature judgment and realistic clinical acumen. PMID- 1749494 TI - Risk factors for infection in fracture war wounds (1973 and 1982 wars, Israel) AB - The development of post-surgical wound infection was compared in two groups of soldiers who sustained fractures or amputations on the battlefield during the first month of the 1982 and 1973 wars. Risk factors for the development of post surgical wound infection were sought. In the 1982 group, numbering 184, the four variables independently associated with infection were multiple operations during the follow-up period; drains inserted in the first operation; extensive tissue loss; and blood transfusion during the first operation. For the 1973 group, numbering 130, the significant variables were multiple operations; amputations (highly correlated with extensive tissue loss); injury involving other body systems in addition to the fracture; and open drains. The high risk associated with open drains in both wars raises doubt about their usefulness. The main distinction between injuries of the two wars was the high prevalence (72.3%) of multi-system injuries in 1973 versus low prevalence (29.2%) in 1982. Overall infection rates were similar (30.5% and 31.5%), but infections at the site of the fracture were twice as high in 1982. Pseudomonas was the most common single species of bacteria isolated from infected wounds (26% in 1982, 33.6% in 1973). It appeared in the wounds relatively late, 10-14 days after admission. PMID- 1749495 TI - Risk factors for stress fractures among Israeli infantry recruits. AB - In order to answer the question of why the stress fracture morbidity rates among Israeli infantry recruits are so high, we prospectively evaluated 392 infantry recruits for risk factors for stress fractures. Prior to training, each recruit underwent a detailed evaluation. Using multivariate analysis, five risk factors for tibial fractures were identified: shorter tibial length (p less than 0.0001); relatively greater valgus knee alignment (p less than 0.002); right leg dominance (p less than 0.02); external rotation of the hip greater than 65 degrees (p less than 0.02); and training in specific subunits (p less than 0.0002., 0.03). No risk factors for femoral stress fracture were found by multivariate analysis. PMID- 1749496 TI - Medical support of the Sinai Multinational Force and Observers: an update, 1990. AB - The Multinational Force and Observers in an 11-nation peacekeeping force established to monitor the 1979 Egyptian-Israeli Treaty of Peace. Provision of medical support for this force was the first employment of the U.S. Army Medical Department in an effort of this kind. This article is an update to "Medical Support of the Sinai Multinational Force and Observers, 1982," published in Military Medicine in October 1983. We compare the execution of medical support in 1982 with that of 1990 and describe medical conditions and problems encountered during our tour. PMID- 1749497 TI - Field assessment of wet bulb globe temperature: present and future. PMID- 1749498 TI - An overview of physical fitness of female cadets at the military academies. PMID- 1749499 TI - Preventative mental health in disaster situations: "terror on the autobahn". AB - As part of Return of Forces to Germany 1990, a number of Second Armored Division soldiers participated in the heroic rescue of German and American civilians injured in a 32-vehicle crash on an autobahn in West Germany. Six people were killed and 18 others were seriously injured at the accident site. This paper (1) briefly reviews acute and chronic stress reactions; (2) describes the accident and rescue; (3) emphasizes specific risk factors for the rescuers; and (4) reviews specific preventative actions that were taken to minimize the risk of future psychologic morbidity in these individuals. PMID- 1749500 TI - A new look at disaster medical assistance teams. PMID- 1749501 TI - Total quality management and the Army health care system. AB - Total quality management (TQM) is the newest in a long line of magic formulas which have been touted as saviors for American industry and medicine. The author discusses the basic concepts of TQM and notes that much of it resembles philosophical beliefs long held by the medical community. TQM does offer many opportunities to refine old concepts and further those goals of quality care to which health care providers have always aspired. If, however, it becomes simply another codified bureaucracy, then a great deal of time and money will be invested for very little gain. PMID- 1749502 TI - Hodgkin's disease at William Beaumont Army Medical Center: survey of practice from 1985 to 1988. AB - We reviewed the records of all patients with a diagnosis of Hodgkin's disease from 1985 to 1988 at William Beaumont Army Medical Center. The clinical presentation, staging, time efficiency to diagnosis and treatment, and survival were analyzed. PMID- 1749503 TI - Surgical management of anorectal infection in the leukemic patient. AB - Anorectal infections are a common complication in immunocompromised patients. Such infections are multifactorial in etiology, often promoted by breaks in the anorectal mucosa and depressed leukocyte counts, both secondary to chemotherapy. Because of altered immune response to infection, diagnosis of anorectal infections in leukemic patients is often delayed, with a resultant mortality of up to 78%. Management is typically supportive for fears of extension of infection or non-healing of wounds with surgical intervention. We recently encountered a 17 year-old woman who presented with an anorectal infection heralding the onset of acute nonlymphocytic leukemia. Because of her unusual presentation, chemotherapeutic induction occurred subsequent to surgical drainage of an anorectal abscess. She demonstrated adequate healing of her wounds in the early post-operative, post-induction period. Her case and a review of the current management of anorectal infections in patients with leukemia are presented. PMID- 1749504 TI - Effort thrombosis: recognition and management while underway. AB - Effort thrombosis of the axillary and subclavian veins is an uncommon cause of upper extremity swelling. Prompt recognition and treatment of this disorder is important in order to minimize the complications of pulmonary embolism and postphlebitic syndrome that can occur with this condition. This can be very challenging while underway or in the field. A sailor who developed effort vein thrombosis while underway on board the aircraft carrier USS Abraham Lincoln is presented to review the presentation and management of this disorder, particularly as it applies to active duty military personnel. PMID- 1749505 TI - Charcot foot osteoarthropathy in diabetes mellitus. AB - Charcot joint, a destructive bone and joint disorder of the foot, is becoming more common in long-term diabetic patients. The combination of diabetic neuropathy and painless trauma causes dislocation and collapse of the tarsal joints. The resulting soft tissue and osseous pathology easily mimics an infective episode. This report presents a review of the clinical identification, diagnosis, and treatment of this unusual diabetic complication, plus a review of three cases. Also, the pathogenesis of Charcot joint is explained in describing why surgery can be a viable treatment alternative in these patients, after careful evaluation. It is also necessary that physicians inspect the feet of their diabetic patients to rule out quiescent beginnings of Charcot joints. Referral to a podiatrist is recommended for long-term management of the Charcot foot. PMID- 1749506 TI - Casualty radiology with lightweight X-ray machine. AB - A small lightweight X-ray machine is needed for use in military medicine for humanitarian service missions, training exercises, and even tactical situations. In such circumstances, the large size and great weight of conventional X-ray equipment limit its use and make this diagnostic modality unsuitable. I have used a small lightweight X-ray machine and obtained adequate X-ray exams in a high percentage of patients. PMID- 1749507 TI - Simulator sickness provoked by a human centrifuge. AB - Simulator sickness is now a well-recognized entity. It is recognized as a form of motion sickness, having a higher incidence in the more sophisticated simulators. Human centrifuges (dynamic simulators) are the newest innovation in aircrew training devices. Simulator sickness has never been reported in human centrifuges. We are reporting on a case of delayed simulator sickness in a pilot subject after a centrifuge experience. A review of the "psycho-physiological" problems routinely experienced by subjects on human centrifuges indicates such problems are due to simulator sickness, although they are not reported as such. In this paper, we give a brief overview of simulator sickness and briefly discuss simulator sickness, as related to the human centrifuge experience. PMID- 1749508 TI - Immunomodulators: a key to controlling infections in military personnel? PMID- 1749509 TI - Sulfated glycoprotein-2 (SGP-2) mRNA is expressed in rat striatal astrocytes following ibotenic acid lesions. AB - A combination of in situ hybridization and immunocytochemistry (ICC) was used to identify the cells that contained mRNA for sulfated glycoprotein-2 (SGP-2) in adult male rats after striatal ibotenic acid (IA) lesioning. Astrocytic responses were monitored by ICC for glial fibrillary acidic protein (GFAP). IA lesioning that caused death of striatal neurons also stimulated astrocytic responses as monitored by GFAP and SGP-2. The SGP-2 immunoreactivity showed punctate deposits in the lesioned striatum without any apparent cellular localization. By in situ hybridization combined with ICC, SGP-2 mRNA was localized in astrocytes that were GFAP-immunopositive. These data suggest that reactive astrocytes may express SGP 2 which may be eventually secreted. PMID- 1749510 TI - A fractal analysis of pyramidal neurons in mammalian motor cortex. AB - Pyramidal neurons in the mammalian cerebral cortex can be described by a fractal dimension (Mandelbrot, 1982), which is an objective, quantitative measure of the complexity of their soma/dendritic borders. In the cat, the fractal dimensions of lamina V cells, which include pyramidal tract neurons (PTN), indicate that these cells are more complex than other pyramidal neurons (PN) in the same region of motor cortex. The lamina V cells of the cat are also more complex than those in motor cortex of the monkey. Moreover, lamina III neurons in the monkey are more complex than monkey lamina V neurons. The fractal dimension of the intracortical axon collateral arborizations of the same pyramidal neurons indicated, in all cases, that the branching of these terminals is less complex than the branching of the dendrites of the same cells. In line with the observation that the fractal dimensions of some homologous cellular populations are different in different species, it is suggested that the fractal dimension and the degree of morphological complexity may relate to the requirement for the number of separable functions to be accommodated within one neuron. For example, as the size of the cortex and the number of neurons in a region increase, the opportunity exists within a given cortical zone, for individual functions to be segregated and for functional specialization to be accommodated with less morphological complexity of the individual neurons performing each of these functions. PMID- 1749512 TI - Membrane bilayer instability and the pathogenesis of disorders of myelin. AB - We have previously shown that total lipid extracts from normal nervous tissues spontaneously form a structure in vitro resembling the cell membrane bilayer, but only at a critical temperature, T*, equal to the 'physiological' temperature of the original tissues. In the present study, we found T* for normal human myelin lipids was 37 degrees C, in agreement with the concept that lipid metabolic pools maintain a critical composition in vivo which permits spontaneous formation of the (myelin) membrane bilayer at normal body temperature. But T* for myelin lipids from a patient with metachromatic leukodystrophy was less than 30 degrees C. Thus, myelin lipid composition was inappropriate for normal bilayer stability at this patient's core temperature, suggesting a mechanism whereby defective lipid metabolism in this disease could produce pathological myelin. The shift in T* in this patient was unlikely to be simply secondary to myelin destruction, as myelin lipids from a patient with advanced multiple sclerosis yielded a normal value for T* of 37 degrees C, even when extracted from areas of extensive demyelination. PMID- 1749511 TI - NGF restores decrease in catalase and increases glutathione peroxidase activity in the brain of aged rats. AB - The effects of subchronic administration of nerve growth factor (NGF) into the lateral ventricle on catalase and selenium-dependent glutathione-peroxidase (GSH Px) activity in several areas of the brain in 3-, 12- and 24-month-old rats were studied. NGF given daily (1 microgram for 28 consecutive days) produced in all brain areas studied a significant increase in catalase activity in 12- and 24 month-old rats. The most important finding was a complete restoration in 12- and 24-month-old rats of catalase activity to levels similar to those occurring in young (3-month-old) rats. In addition, NGF produced in comparison to 3-month-old rats and to same age vehicle-treated rats a significant increase in selenium dependent GSH-Px in all the brain areas studied in 12- and 24-month-old animals, whereas selenium-independent GSH-Px was unaffected. In conclusion, the present results show that long-term administration of NGF into the lateral ventricle significantly increases in old animals the activity of key enzymes involved in the metabolic degradation of hydrogen peroxide. PMID- 1749513 TI - Activation of spinal neurons by afferent fibers in the ventral roots of rats. AB - The present investigation was aimed to search for spinal neurons which are activated by afferent fibers in the ventral roots, and once found, to study their receptive field and rostral projection. After dorsal roots L1-S4 on the left side were cut, ventral roots were stimulated to record extracellular responses of the neurons using glass microelectrodes filled with Fast green FCF. Thirty-nine neurons were activated by stimulating ventral roots at 2.5-26.7 x threshold (T) of the lowest threshold fibers of the ventral root. Six neurons were classified as wide dynamic range neurons and 16 high threshold neurons according to their response patterns to the periphery. Seventeen neurons were unresponsive to cutaneous stimulation, suggesting they had innervated visceral organs. Most of the neurons (71%) were located in layer V and VI. In 7 neurons (18%), rostral projection was confirmed by collision block method and ability to respond to high frequency stimuli with constant latency. PMID- 1749514 TI - Influence of oxygen availability on the neurotoxic effect of 6-hydroxydopamine on nigro-striatal dopaminergic neurons. AB - The neurotoxin 6-hydroxydopamine (6-OHDA) was intracerebroventricularly injected (50 micrograms per mouse) in mice submitted to various oxygenation conditions and the striatal levels of dopamine (DA) and its metabolites were determined by HPLC 7 days later. In normoxic conditions the striatal depletion in DA reached 50%. This effect was not modified by a normobaric hypoxia (10% O2) applied 30 min before and 30 min after the 6-OHDA injection. On the contrary, the neurotoxic effect was reduced when the hypoxia was prolonged up to 11 h after the drug administration. When a normobaric hyperoxia (60% O2) was applied 30 min before and 11 h after the 6-OHDA injection, the neurotoxic effects of the latter were not modified. These data, as well as other results obtained from ex vivo experiments showing that normobaric hypoxia or hyperoxia did not modify the striatal synaptosomal [3H]DA uptake, indicate that oxygen availability does not exert a critical influence on the efficiency of the neuronal dopamine uptake complex. PMID- 1749515 TI - Carbachol microinjections in the mediodorsal pontine tegmentum are unable to induce paradoxical sleep after caudal pontine and prebulbar transections in the cat. AB - In 7 cats, total transections of the brainstem at the caudal pontine or the prebulbar level led to preparations which presented neither behavioral nor electrophysiological signs of paradoxical sleep (PS) throughout their survival periods (17-30 days). Carbachol microinjections in the mediodorsal pontine tegmentum (MDPT), which induced PS in the intact cat, were no longer able to induce it in the transected animals. Rapid eye movement (REM) and pontogeniculo occipital (PGO)-like bursts were evoked by carbachol microinjections in the pontine magnocellular tegmental field (FTM) of cats transected at the prebulbar level, as in the intact cat. Only REM bursts were obtained by the same injections in caudal pontine transected cats. It is concluded that (1) the pons is insufficient to generate PS; (2) complex reciprocal interactions with the medulla are necessary for the generation of this state of sleep; and (3) the production of long REM and PGO bursts is controlled by the caudal pontine tegmentum. PMID- 1749516 TI - Effect of ketone body (D-3-hydroxybutyrate) on neural activity and energy metabolism in hippocampal slices of the adult guinea pig. AB - The role of ketone body on neural activity and energy metabolism in the brain was investigated. Guinea pig hippocampal slices were prepared, and postsynaptic field potentials (PSPs) were recorded in the granular cell layer of the dentate gyrus. ATP and phosphocreatine (CrP) in the tissue slice were measured after 60 and 120 min incubation in standard medium (1) with 10 mM glucose, (2) with 10 mM glucose plus 20 mM D,L-3-hydroxybutyrate (3-OHBA), (3) without glucose, (4) with 20 mM 3 OHBA instead of 10 mM glucose. In (3), both ATP and CrP in the slice decreased to 40-45% of the original level after 120 min. On the other hand, the ATP level was well maintained even 120 min after incubation in (1), (2) and (4), whereas the CrP level decreased to 62% in (4). Further, slices were incubated in (3) and (4) for 30, 60, and 120 min, and the presence of PSP was tested. In (3), the number of slices from which PSPs could be recorded decreased, and after 120 min PSPs were hardly observed. In (4), that number decreased gradually, and only 45% of the slices showed PSPs after 120 min. These results indicate that 3-OHBA can be a substrate to produce high-energy phosphate but cannot maintain the neural activity as glucose does. PMID- 1749517 TI - Alteration of second messenger systems after transient cerebral ischemia in gerbils: protective effect of pentobarbital and an autoradiographic analysis. AB - The postischemic alteration of second messenger systems in the gerbil brain was analyzed by receptor autoradiography using [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]inositol 1,4,5-trisphosphate (IP3). The alteration of the [3H]PDBu binding in striatum and hippocampus was milder than that of the [3H]IP3 binding 5 h and 7 days after 10-min ischemia. The administration of pentobarbital prevented a decrease in the [3H]IP3 binding sites in all areas 5 h and 7 days after ischemia. These results suggest that the disruption of intracellular calcium homeostasis may play an important factor in ischemic brain damage. PMID- 1749518 TI - Phosphorylation of pyruvate dehydrogenase in the hippocampal slice: time course of response to cellular depolarization. AB - In the rat hippocampal slice, we evaluated the effects of potassium depolarization on phosphorylation of the alpha subunit of the pyruvate dehydrogenase complex (E1 alpha, mol. wt. approximately 41 kDa) using an in vitro back-titration assay. The in vitro back-titration phosphorylation of El alpha was maximal following 30 s of depolarization and remained elevated for up to 3 min following termination of the depolarizing pulse. Possible significance of and mechanisms for the depolarization-induced changes in E1 alpha phosphorylation are discussed. PMID- 1749519 TI - Reversible decrease of fluoride resistant acid phosphatase-positive neurons after herpes simplex virus infection. AB - Herpes simplex virus (HSV) frequently infects human sensory ganglion neurons, and similar infections have been reported in experimental animals. Reported here is an investigation of in vivo neuronal function after HSV infection. It was observed that the proportion of fluoride resistant acid phosphatase (FRAP) positive trigeminal ganglion neurons was decreased for several months after experimental infection of mice, and it is suggested that other neuronal functions may also be altered by HSV. PMID- 1749520 TI - Short biotinylated oligonucleotides bind non-specifically to senile plaques of Alzheimer's disease. AB - We have used in situ hybridization with biotinylated oligonucleotide (antisense) probes and streptavidin-biotinylated alkaline phosphatase method to detect the amount of amyloid beta-protein mRNA in the paraffin-embedded and formalin-fixed brain samples of patients affected by Alzheimer's disease and those of non affected controls. Instead of the expected specific binding to neuronal cytoplasm, the probes did constantly bind to neuritic senile plaques, the strongest binding being found in the hippocampus and the cerebral cortex. We have been able to constantly repeat this peculiar phenomenon with other (30-mer) oligonucleotide probes, e.g. the sense probes for beta-amyloid protein and those specific for human papillomavirus (HPV) 18- and c-erb B-2 mRNAs. Replacing the probe with water as a negative control lead to abolishment of the colour reaction, thus excluding the possibility of the non-specific staining being due to the detection system. This confirms that the oligonucleotide probe is essential for this binding phenomenon. PMID- 1749521 TI - Is balance or posture at the end of a voluntary movement programmed? AB - Two leg movements, differing only by the final balance conditions, were analysed to determine whether the final body posture or the equilibrium were taken into account by the motor programming. The test movement was a flexion-extension of a lower limb executed at maximal velocity. The initial body posture was bipedal, while the final one was either bipedal or unipedal. The biomechanical and electromyographic data showed significant differences between parameters of the two movements. The results indicate that the final body equilibrium is the major parameter controlled. PMID- 1749523 TI - License suspension. PMID- 1749522 TI - Retinal lesion by bright artificial light increases vasoactive intestinal polypeptide in the rat ventral tegmental area/substantia nigra. AB - Sprague-Dawley rats were treated with bright light to induce retinal lesions and vasoactive intestinal polypeptide in the ventral tegmental area/substantia nigra was measured by radioimmunoassay. In Sprague-Dawley rats, but not in Brown Norway rats where light did not induce retinal lesions, significantly increased concentrations of vasoactive intestinal polypeptide were found 21 days after exposure with bright light. This increase declined to control values 60 days after the treatment. Our studies indicate that vasoactive intestinal polypeptide may be involved in visual neurotransmission and that the ventral tegmental area/substantia nigra may be connected to retinal input. PMID- 1749524 TI - The study of cancer in minorities. AB - Data inventories provide a concise reference base for researchers. The authors created a set of reference volumes listing databases used for studying cancer in New Jersey minorities. The process followed can be adapted for other disease outcomes or other regions. PMID- 1749525 TI - Tonsillar polypoid lymphangioma in a small child. AB - The authors report a case of an unusual tonsillar polypoid lymphangioma in a three-year-old child. A discussion of the possible mechanisms of its pathogenesis is included, as well as a review of the literature of benign lymphangiomatous tonsillar lesions. PMID- 1749526 TI - Prostatic cancer: the case for conservatism. AB - Carcinoma of the prostate is the most common malignancy in men. It is the second leading cause of cancer deaths in men, with a five-year survival rate of 72 percent. One asks, "Is the cure necessary in those in whom it may be possible? Is cure possible in those whom it may be necessary?" PMID- 1749527 TI - Diet, nutrition and the prevention of chronic diseases. A report of the WHO Study Group on Diet, Nutrition and Prevention of Noncommunicable Diseases. PMID- 1749528 TI - The osteocalcin gene promoter: stimulated by vitamins A and D, inhibited by cell growth factors Jun-Fos. AB - The gene of the bone protein osteocalcin has a promoter region recognized by the receptors for 1,25-dihydroxyvitamin D3 and retinoic acid, both of which stimulate transcription. Unexpectedly, this same gene element interacts with the cell proliferation factors Jun-Fos, which inhibit osteocalcin gene transcription. PMID- 1749529 TI - Iatrogenic liver disease from vitamin A. AB - In a retrospective case series, 41 patients developed severe liver disease after prolonged administration of vitamin A originally recommended for the treatment of medically benign conditions, mostly dermatologic. Six patients died of liver failure during follow-up. PMID- 1749530 TI - Behavioral consequences of pyridoxine deficiency in mothers and infants. AB - Maternal vitamin B6 status correlates birth weight with infant behavior and maternal infant interactions. PMID- 1749531 TI - Folate deficiency and pregnancy outcome. AB - The degree of folate deficiency can be manipulated in rats by the extent of exposure to a deficient diet. In turn, this can affect pregnancy outcome and neonatal health. PMID- 1749532 TI - Lowering cholesterol with diet and lovastatin. AB - The addition of lovastatin to a high- and a low-fat diet produces a comparable percentage improvement in plasma lipoprotein profiles. However, lower absolute lipid and lipoprotein levels are achieved by adherence to a low-fat diet. PMID- 1749533 TI - A short course of intravenous nutrition in inflammatory bowel disease improves respiratory and skeletal muscle function. AB - In malnourished patients hospitalized because of acute exacerbations of inflammatory bowel disease, a brief course of intravenous nutrition can restore skeletal and respiratory muscle function even before body protein has been repleted. PMID- 1749534 TI - New insights on prolactin function. AB - A new rat model for the study of hyperprolactinemia has been developed by subcutaneous injection of a prolactin-secreting pituitary tumor cell line. Hyperprolactinemia caused excess urinary calcium. Bone loss in this animal model may be associated with suppressed calcium levels or an effect of prolactin on renal calcium reabsorption. PMID- 1749535 TI - Nutritional resilience in a hostile environment: positive deviance in child nutrition. AB - The term "positive deviance" applies to the study of children who demonstrate above-average growth in impoverished environments. Favorable values on known malnutrition correlates and attentive child care characterize positive deviants. Best-growing children do not necessarily mirror the malnourished; for example, best- and worst-nourished infants may both get more breast-milk substitutes than middle growers. Positive deviants receive more high-quality foods, physical interaction, affection and praise, and verbal and environmental stimulation. Factors that influence child growth through care quality also predict cognitive development, health, and social adjustment. They include: the type of society; parental education, mental health, initiative, and work burden; family and community structure; and the value of children to parents. Feeding practices related to growth include: permitting the child to control the length of feeding, encouraging eating while avoiding a power struggle, actively spoon- or hand feeding, not displacing appetite by giving frequent sweets, and timely introduction of appropriate foods. PMID- 1749536 TI - The American Journal of Clinical Nutrition, Volume 25, 1972: Influence of recurrent infections on nutrition and growth of children in Guatemala. PMID- 1749537 TI - United States Nutrition Labeling and Education Act of 1990. PMID- 1749538 TI - Different effects of dietary saturated fatty acids on cholesterol metabolism in nonhuman primates. AB - Dietary saturated fatty acids did not act alike in their effect on plasma cholesterol concentrations in non-human primates. Palmitic acid was less hypercholesterolemic than lauric plus myristic acids. Myristic appeared to be a greater offender than lauric. PMID- 1749539 TI - Energy intake restriction and oxidant defense. AB - Caloric restriction alters the expression of genes in rat liver that code for oxidant defense enzymes. Dietary restriction also reduces ethane production, an index of in vivo lipid peroxidation. PMID- 1749540 TI - All-trans and 13-cis-retinoic acids are normal constituents of human blood formed from all-trans-retinyl palmitate. AB - All-trans and 13-cis-retinoic acids are normal constituents of human blood. Blood levels of both compounds increase upon oral ingestion of all-trans-retinyl palmitate, to a greater extent with higher amounts of ingested retinyl palmitate. These data suggest a mechanism whereby levels of dietary vitamin A could influence blood levels of the known cancer chemopreventive retinoic acids. PMID- 1749541 TI - Folate deficiency, parenteral caffeine, and cytogenetic damage in mice. AB - Chromosomal damage can be detected in bone marrow or peripheral red blood cells in the form of micronuclei. In mice, folate deficiency increased the frequency of micronuclei in erythrocytes. Intraperitoneal caffeine administration, in the setting of folate deficiency, increased the risk of cytogenetic damage in rodents. PMID- 1749542 TI - The influence of tea on iron and aluminum bioavailability in the rat. AB - The aluminum from tea or tea leaves was very poorly absorbed by young, growing rats. Tea had a decidedly adverse effect on the animals' iron status. PMID- 1749543 TI - Keep potassium chloride off your unit. PMID- 1749544 TI - My most treasured Christmas gift. PMID- 1749545 TI - H.I.V.-positive nurse tells her story. PMID- 1749546 TI - Obstructed airway with wired jaws. PMID- 1749547 TI - Protecting yourself from allegations of nursing negligence. PMID- 1749548 TI - Pain control a top priority. PMID- 1749549 TI - The doctor was wrong. PMID- 1749550 TI - How much do you know about laboratory studies? PMID- 1749551 TI - Sandra was a rebellious teenager in a wheelchair. PMID- 1749552 TI - New drugs. PMID- 1749553 TI - Hypomagnesemia correction. PMID- 1749554 TI - Nurs/patient ratio too high. PMID- 1749555 TI - Shedding light on i.v. therapy. PMID- 1749556 TI - Keeping hope alive. PMID- 1749557 TI - Dealing with a hidden hazard: M.R.S.A.--methicillin-resistant Staphylococcus aureus. PMID- 1749558 TI - Using an aquathermia pad safely. PMID- 1749559 TI - My applesauce lady. PMID- 1749561 TI - Are you a good follower? PMID- 1749560 TI - Managing the patient with diabetes. PMID- 1749562 TI - Breathe new life into your career. PMID- 1749563 TI - Abstracts of the fifteenth annual meeting of the Japan Neuroscience Society, Tokyo, Japan, December 17-19, 1991. PMID- 1749564 TI - AIDS and the ADA. PMID- 1749565 TI - The changing face of dental students. AB - Today's dental students are more diverse than typical. What they have in common, however, is a desire for independence and stability in an increasingly more complex profession. PMID- 1749566 TI - Papillon-Lefevre syndrome. AB - Papillon-Lefevre syndrome is a particularly devastating disease that eludes all forms of therapy. It challenges researchers to find a connection between the dermatologic aspects of the disease and the severe periodontosis resulting in an edentulous patient in just a few years. PMID- 1749567 TI - Dentistry is making a career comeback. AB - Technology took some of the bloom off dentistry as a career choice. Ironically, it's the same force that has given new status to the profession and made dentistry the career of the future. PMID- 1749568 TI - The dental assistant. The case for recognition. PMID- 1749569 TI - Restorative needs and pathological findings in northern Manhattan dentate community. AB - When determining the dental health of the population, radiographic findings cannot be omitted. Nor should large groups of people be left out as this affects the results significantly. PMID- 1749570 TI - Dentists and pharmacy law. PMID- 1749571 TI - New health department policy supports DSSNY position. PMID- 1749573 TI - Medicaid Search Committee formed. PMID- 1749572 TI - First district office is target of takeover. PMID- 1749574 TI - The future of science and medicine. PMID- 1749575 TI - U.S. Senate adds AIDS amendments. PMID- 1749576 TI - 10 years of AIDS in Ohio. PMID- 1749577 TI - Physician responsibilities under new living will law. PMID- 1749578 TI - Tissot's twist in taste. PMID- 1749579 TI - Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies. AB - The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients. PMID- 1749580 TI - Treatment of myelodysplastic syndromes with orally administered 1-beta-D arabinofuranosylcytosine-5'-stearylphosphate. AB - 1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS. PMID- 1749581 TI - Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP). AB - Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease. PMID- 1749582 TI - Ifosfamide, methotrexate and 5-fluorouracil for pretreated advanced breast cancer. AB - A total of 51 fully evaluable patients with advanced and intensively pretreated breast cancer were treated with a combination chemotherapy of ifosfamide plus mesna, methotrexate and 5-fluorouracil. All patients had received at least one series of combined chemotherapy, 30 patients had received more than one combination and 41 patients had had anthracyclines before. Metastatic lesions in more than one site were found in 42 patients, and 24 patients had metastatic liver lesions. Partial remission was achieved in 10 patients (20%) and no change in 16 patients (31%). Survival was almost identical in both groups of responding patients and significantly shorter in treatment failures. Response was favorable in patients without pretreatment with anthracyclines. Two patients who received this protocol directly after progression with cyclophosphamide, methotrexate and 5-fluorouracil (CMF protocol) responded with a partial remission. Median time to progression was 7 months for partial responders and 4.5 months for patients achieving a no-change status. Median survival was 8 months for all patients. Toxicity was tolerable. Leukocytopenia and thrombocytopenia were treatment limiting parameters. Overall, this protocol is well tolerable and effective in breast cancer patients with advanced disease and in intensively pretreated patients. PMID- 1749583 TI - Immunologic changes in renal cell carcinoma patients receiving gamma interferon. AB - Immunologic changes were monitored in 5 patients with metastatic renal cell carcinoma participating in a phase II trial of recombinant interferon gamma (rIFN gamma). Treatment consisted of a 4-week period of intravenous infusion of either 0.1 mg/m2 given over 4 h on alternate days (3 times/week) or 2 mg/m2 given over 1 h for 5 days every other week. One minor response was seen at the higher dose level and toxicity was minimal (grades I-II). Absolute leukocyte counts and lymphocyte subpopulations did not change significantly. Both natural killer cytolytic activity and spontaneous monocyte-mediated tumoricidal activity increased. Prostaglandin E2 synthesis of patient leukocytes was abnormally high and pretreatment levels dropped during treatment. Data suggest that rIFN gamma may be potentially useful for enhancing immunologic function in renal cell carcinoma. PMID- 1749584 TI - Modulation of methotrexate cytotoxicity with natural interferon upon human leukemia cell line HL-60. AB - The effect of alpha- and gamma-interferon on methotrexate cytotoxicity against human promyelocytic cell line HL-60 has been evaluated. Synergistic inhibition of proliferation is observed with the combination of methotrexate and gamma interferon. Enhanced cytotoxic effect of methotrexate with alpha- or gamma interferon is removed by adding thymidine to the growth medium. The depletion of folate pools caused by methotrexate is enhanced in presence of interferons, this depletion is also removed by adding thymidine to the growth media. Synchronization of HL-60 cells in 'S' phase of cell cycle caused by methotrexate is enhanced in the presence of interferons. These results suggest that specially gamma-interferon changes the cellular environment of HL-60 cells in such a way as to make methotrexate more potent cytotoxic agent to HL-60 cells causing cell death. This study also clearly indicates the biochemical role of thymidine in modulating the activity of methotrexate in combination with interferons. PMID- 1749585 TI - Protective effect of elastase on cis-platinum-induced renal toxicity. AB - The protective effects of elastase (Ela) and fosfomycin against renal toxicity of cis-diamminedichloroplatinum (II) (CDDP) were evaluated in an experimental study using rats. When Ela was used concomitantly with CDDP, the elevation of urinary N acetyl-beta-D-glucosaminidase levels in the early phase and the sharp fall in these levels in the latter phase were prevented. It was also found that the blood urea nitrogen levels and serum creatinine levels were significantly lowered. Histologically, atrophic and necrotic changes in the tubular epithelium were prevented. The total serum platinum levels showed no change with the addition of Ela; however, the platinum levels in the renal tissues were significantly reduced. These results suggested that Ela is effective against platinum deposits in the renal tissues, particularly in the tubular epithelium, thus protecting the kidneys. On the other hand, fosfomycin demonstrated no such positive results suggestive of a protective effect on the renal function parameters or during histological observation. PMID- 1749586 TI - Nasopharyngeal carcinoma: role of marrow biopsy at diagnosis. AB - Twenty-seven new patients with advanced nasopharyngeal carcinoma were evaluated by marrow biopsy at diagnosis. The marrow trephines and blood clots were evaluated by morphology and immunohistochemical studies for cytokeratin and found negative in all cases. The median follow-up of this group of 27 patients was 22 months, and 7 of them had relapsed in the skeletal system. We conclude, in view of its poor sensitivity, that routine use of marrow biopsy for the staging of nasopharyngeal carcinoma is not recommended. PMID- 1749587 TI - Follicular cancer of the thyroid gland. AB - Between 1965 and 1987 the authors studied the survival of 169 patients (130 females, 39 males) suffering from follicular thyroid cancer. It is established that the factors favorably influencing the course of the disease are as follows: age below 40 years, female sex, tumor location inside the thyroid capsule. Radical surgery does not affect the survival, though it prolongs the time to the onset of metastases. In women below 40 years of age, iodine treatment performed within 1.5 months following surgery does not increase the effectiveness; therefore, its routine application is not recommended. In case of local metastases associated with hindered swallowing or respiration, external beam radiotherapy is indicated. Hormone substitution ensuring TSH restriction results in improved prognosis. PMID- 1749588 TI - Diet and urine estrogens among postmenopausal women. AB - Creatinine-adjusted levels of estrone, estradiol and estriol were determined in overnight urine specimens from 88 postmenopausal women from Athens, Greece, and were correlated with daily nutrient intakes estimated through a semiquantitative food frequency questionnaire. Although obesity was positively and significantly related to all three urinary estrogens and their total, none of the investigated macro- or micronutrients was significantly or suggestively associated to any of these urinary estrogens, after controlling for energy intake, reproductive and biosocial variables. These results suggest that quantitative rather than qualitative aspects of nutrition affect the levels of postmenopausal estrogens, although endogenous factors could also be responsible for the association of these estrogens with obesity. Alcohol intake was also positively associated with urinary estrogens (mainly estrone and estradiol), after controlling for energy intake, obesity and the other indicated variables. PMID- 1749589 TI - Reticulum cell sarcoma: two complete 'spontaneous' regressions, in response to high-dose ascorbic acid therapy. A report on subsequent progress. AB - In 1975, we reported the remarkable case of a 42-year-old man with histologically proven widely disseminated reticulum cell sarcoma who, in a remarkably short time, appeared to enjoy not one, but two, complete spontaneous regressions of his fatal illness. Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses. For those interested in spontaneous regressions of cancer and the possible mechanisms, we now report his subsequent progress some 17 years later. PMID- 1749590 TI - Effects of combined therapies with protein-bound polysaccharide (PSK, Krestin) and fluorinated pyrimidine derivatives on experimental liver metastases and on the immunologic capacities of the hosts. AB - An experimental model is introduced for the study of liver metastases using intrasplenically injected EL-4 and Lewis lung tumor cells. Fluorinated pyrimidine derivatives, 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil, showed inhibitory effects on the frequencies of liver metastases. Immunosuppressive effects of these drugs were compared at the doses capable of showing 50% inhibition of the development of metastatic nodules. These derivatives strongly suppressed the phagocytic activity and the number of Kupffer cells of the liver and then the humoral response against sheep red blood cells, the delayed hypersensitivity against picryl chloride. On the contrary, combined administration of protein-bound polysaccharide (PSK) and 1-(2-tetrahydrofuryl)-5 fluorouracil showed no inhibitory effect on these activities. PMID- 1749591 TI - Effects of retinoid glucuronides on mammary gland development in organ culture. AB - Retinoyl beta-glucuronide (RAG) and retinyl beta-glucuronide (ROG) inhibit prolactin-induced morphological developments in cultured mouse mammary gland, and are equally effective in depressing prolactin and steroid hormone-induced DNA synthesis in the same tissue. Retinol is essentially inactive by both assay methods. Although RAG and ROG show little or no toxicity in several cell and animal models, some possibly toxic manifestations were seen at higher concentrations in cultured mammary tissue. Nonetheless, because of the strong correlation between the actions of chemopreventive agents in culture mouse mammary glands and their effectiveness in vivo, the retinoid glucuronides may well prove to be useful cancer chemopreventive agents. PMID- 1749592 TI - Fractional incorporation of radionucleotides, a marker of in vitro tumor cell chemosensitivity in colorectal cancer. AB - Working with the antimetabolic chemopredictivity assay on short term cultures we evidenced a correlation between in vitro chemosensitivity of colorectal cancer and fractional incorporation of radionucleotides. Four different drugs (5-FU, mitomycin C, 4'-iododeoxydoxorubicin and ruboxyl, a nitroxyl derivative of daunorubicin) were tested on 102 tumor cultures. The extent of 3H-TdR and 3H-UdR incorporation into DNA and RNA in the related control cultures was in relationship with the chemosensitivity of the tumor. Along with the labeling index this simple metabolic-kinetic trait may gain a role for the screening of tumor phenotypes sensitive to chemotherapy. PMID- 1749593 TI - Glenn A. Fry Award Lecture 1990: three perspectives on low vision reading. PMID- 1749594 TI - Computerized contact lens fitting. AB - A keratometer with a standard and a large mire was used to estimate the corneal apical radius and p value. A computer program used this information to determine an optimum fitting contact lens. A fitting set was used independently to determine the optimum contact lens by conventional clinical assessment. The two approaches were in broad agreement, but the computerized approach was quicker. However, calculations revealed that in this group of subjects standard keratometry provides a good estimate of the equivalent sphere which is used to determine the optimum back optic zone radius in the computerized approach. PMID- 1749595 TI - Quantity of protein deposited on hydrogel contact lenses and its relation to visible protein deposits. AB - The purposes of this study were to determine if the quantity of protein deposited (QPD) upon hydrogel lenses was affected by enzymatic cleaning and to test the potential relation between QPD and visible protein deposition (VPD) and change. Seventy-four contact lens patients classified as "heavy depositors" wore new lenses for an average of 80 (SD = 32) days. Cleaning and disinfection solutions varied. One lens was cleaned weekly by a papain enzymatic treatment. The distribution of QPD measurements was bimodal and was related to the FDA material for nonionic, low water content lenses (FDA Materials Group no. 1). The mean deposition was 45 micrograms/cm2 (N = 112) compared with that of ionic, high water content lenses (FDA Materials Group no. 4), which was 1010 micrograms/cm2 (N = 30). VPD distributions were the same for the FDA Group no. 1 and no. 4 lenses. Enzymatic treatment did not significantly reduce QPD; however, enzymatic treatment did reduce VPD. Thus QPD and VPD are independent phenomena and possible reasons for this are given. PMID- 1749596 TI - Hydrogel lens water content and the stability of the prelens tear film. AB - Using a noninvasive method, the stability of the tear film over a hydrogel lens appears to be related to its water content. The clinical and practical relevance of the findings are discussed. PMID- 1749597 TI - Aging-related foveal flicker sensitivity losses in normal observers. AB - Photopic flicker sensitivity for healthy subjects over 60 years of age was compared with that of subjects in their 20s and 30s. The stimulus was achromatic and viewed foveally through a 2.0-mm artificial pupil which assured a constant pupil size in all subjects. As a group, older subjects had lower flicker sensitivity than younger subjects. This was found even when the retinal illuminance difference between age groups that arises from increased lens absorption in older adults was taken into account. The results indicate that a reduction in retinal illuminance with age cannot account for all the flicker sensitivity losses in older adults. PMID- 1749598 TI - Spatial contrast sensitivity in Alzheimer's disease: a comparison of two methods. AB - The present study was designed to compare the contrast sensitivity functions (CSF) obtained with the Nicolet CS2000 and the Vistech VCTS6500 for a sample (N = 25) of patients diagnosed with probable Alzheimer's disease (AD) and a sample (N = 25) of healthy elderly adults. With the Nicolet, CSF were determined for gratings presented under static and rapidly counterphased (7.5 Hz) conditions. All research participants were able to complete the Vistech test. However, 13.7 and 7.4% of the original samples of Alzheimer patients and healthy adults, respectively, did not yield usable data. Both test instruments showed uniformly low contrast sensitivities for the AD group. The results support the proposition that AD involves a primary visual disturbance and suggest that the Vistech chart can be used with a broader range of patients for initial screening. PMID- 1749599 TI - Reading speed through different equivalent power low vision devices with identical field of view. AB - Adequate reading speed is one of the criteria low vision patients may use to assist them when they are comparing and selecting equivalent power low vision devices. Inherently, various optical devices of equivalent power will produce different fields of view. We compared the reading speed of 32 trained, normal observers with 4 commonly prescribed types of low vision devices of +12 D equivalent power (spectacles, hand magnifier, stand magnifier, and telemicroscope) which were modified to provide nearly identical fields of view. Our results show that only the reading speed obtained with the telemicroscope was significantly different from those of the other systems (p less than 0.01). Implications are that the field of view provided by a low vision device is the primary parameter limiting reading speed of equivalent power devices. PMID- 1749600 TI - Tear characteristics of the VDU operator. AB - The volume and stability of the tear film was measured in a small group of Visual Display Unit (VDU) operators and a non-VDU operating group. Using noninvasive methods of tear measurement, we found no difference in precorneal tear film stability between the two groups; however, the tear volume of the VDU users was greater than in the non-VDU operating group. No relation was found to exist between precorneal tear film stability and tear volume. PMID- 1749601 TI - Binocular interaction with neutral density filters as measured by the visual evoked response. AB - The influence of neutral density (ND) filters on the pattern visually evoked response (VER) was investigated as a function of check size. Monocular and binocular transient pattern reversal VER's were recorded through three ND filters (0.6, 1.0, and 2.6 log units) before 1 eye on 55 adult subjects using 5.5 min arc and 50 min arc check sizes. The 5.5 min arc check produced responses which suggest that partial binocular summation is present in the absence of ND filters but disappears as the filter density increases. In the case of the 50 min arc check size the presence of binocular summation is less certain and a 1.0 log unit ND filter produces binocular inhibition which may be due to latency differences between the two eyes. Eye dominancy appears to have no effect on these results. PMID- 1749602 TI - Anomalous kinetic visual fields found in family members of patients with a confirmed diagnosis of Gilles de la Tourette syndrome. AB - Three visual manifestations of Gilles de la Tourette syndrome (TS), a neuropsychiatric disorder, have been previously reported. In this paper we report anomalies in the measured kinetic paracentral visual field of TS patients and their family members. We found that 96% of TS patients exhibited paracentral kinetic visual field defects (nasal and temporal steps, enlargement, "ringing," and/or baring of the blind spot). Ninety-three percent of fathers of TS children and, surprisingly, about 80% of mothers exhibit these characteristic visual field anomalies. Sample data and examples of family studies are reported. PMID- 1749603 TI - Changes in ocular astigmatism over the whole range of accommodation. AB - The refraction of 20 subjects was measured over the whole range of accommodation using an objective automated refractometer in order to investigate the astigmatic change whose origin is presumed to be at the lens. For this purpose, the corneal vertex was used as the plane of reference to avoid changes in the optical effectively of a cylindrical lens at near. The change in the astigmatism with accommodation was observed in each subject. Subjects were then divided into three groups: (1) seven subjects showed an increase in astigmatism with accommodation; (2) eight subjects showed constant astigmatism up to the accommodative nearpoint; and (3) five subjects showed other types of change, such as reduced astigmatism in the intermediate accommodative state. These variations suggest that accommodative astigmatism is affected by many elements such as lens, zonule, and muscle. Two of 20 subjects could see the vertical line of the visual target composed of many directional lines clearer than the horizontal line at distance. Conversely, they could see the horizontal line clearer than the vertical line at near. We also studied the correspondence between the dark focus of accommodation and the dioptric distance where astigmatism is at a minimum, as suggested previously. The results showed that no such direct relation existed. PMID- 1749605 TI - Lens power matrices and the sum of equivalent spheres. PMID- 1749604 TI - Inhibition of binocular contrast sensitivity in hypermetropic anisometropia. AB - Binocular contrast inhibition can occur when the monocular contrast sensitivities are not equal. It has been reported in cases of monocular cataracts. Our case is an 18-year-old female with 3.50 D of hypermetropic anisometropia. She was not amblyopic but showed a typical binocular contrast inhibition. PMID- 1749606 TI - Clinical experience in halting myopia. PMID- 1749607 TI - [The computer and the orthodontist]. PMID- 1749608 TI - [Esthetics of the face and teeth]. PMID- 1749609 TI - [Esthetics and orthodontics]. PMID- 1749610 TI - [Functional hierarchy and mandibular esthetics]. AB - The purpose of the present study based on the comparison of two populations showing a different average of age, was to see the possible action of the tongue on the mandibular morphology. This study included the examination of norma lateralis teleradiographs, while both facial and lingual musculatures were in rest position. If it appears that older subjects show a close correlation between mandibular divergence and lingual height, this relation doesn't take place in younger subjects although they present an earlier mandibular hyperdivergence. May breathing, a function hierarchically of the highest importance be more determinant in lower face organisation than deglutition and lingual equilibrium? PMID- 1749611 TI - [Prognostic factors of treatment results through diagnostic and therapeutic elements]. AB - A file including 559 treated patients, from whom the result of treatment is know, is analysed. It concerns 52 diagnostic and 7 therapeutic variables. The statistic analysis is executed in particular by scoring method. It allows to identify the 8 most discriminating variables relating to orthodontic prognosis. The ANGLE Class presents an essential weight. The other 7 variables differently interfer according to ANGLE Classes. PMID- 1749612 TI - [Morphogenetic normalization, the contribution of orthodontics]. PMID- 1749613 TI - [A comparative study of cephalometric evaluation criteria of the cutaneous profile]. AB - The objectives of this study is to challenge the soft tissue profile standards of esthetics and to compare them with the feeling and the sense of beauty of the large public. The facial profile of one hundred fifty-two cinema stars and top models (seventy-one men and eighty-one women) were analysed. Twenty three measurements were taken among the most used and widely accepted. These references come from the works of very reknown orthodontists and researchers: BURSTONE, HOLDAWAY, MERRIFIELD, PECK and PECK, RICKETTS, STEINER, WORMS (as described by MOSHIRI). The results demonstrate, after statistical analysis that: some values are very different compared with the references; those discrepancies neither concern the same values nor for the same amount, or to the same direction for the male or the female samples. The mean male soft tissue profile is more concave, prognathic type with more retruded upper and lower lips and more reduced lower face height than the standards described by the authors. The mean women soft tissue profile tends to be more convex with a relatively more protruded upper lip and a more retrognathic mandible than the "standards". The whole face height is significantly reduced with a more marked discrepancy for the nasal height and the lower lip length. The nasal prominence is also reduced compared with the norms. It appears then that we cannot trust anymore references that do not take into account differences between men and women ideal facial profiles for the analysis of soft tissue profile in orthodontics and maxillo-facial surgery. The values described by the authors, which are our daily standards, do not seem to match the large public sense of esthetics and therefore our patients feeling of beauty. PMID- 1749614 TI - [The therapeutic smile: orthodontics, surgery and mental attitude]. PMID- 1749615 TI - [Esthetics and bioprogressive therapy]. PMID- 1749616 TI - [Labial incompetence. Therapeutic considerations of esthetic and functional deficits]. AB - The lips constitute an anatomic, physiologic and aesthetic specific entity which is integrated between nasal and chin areas. Inocclusion of the lips at rest forms an anomaly which affects mandibular growth, lip function and facial morphology. This vertical labial dysharmony implies on one hand an architectural skeletal unbalance at inferior third of the face, mostly associated with dento-alveolo maxillary disturbance, on the other hand a disorder of oro-facial muscular behaviour. The treatment's aim is the restoration of a spontaneous lip seal at rest. It will be institute as early as growth-hood using functional orthopaedic devices. In adolescent and adult, the correction of existing dento-alveolar dysharmonies by orthodontic means will be completed, if necessary, by surgical procedures either orthognathic correcting retrognathism or maxillary anterior alveolar hyperplasia with dental extrusion, or morphologic to achieve elongation of congenital upper short lip or elevating of lower lip attracted towards the chin. Orthopaedic and morphologic analyses are necessary to locate the site of the responsible anomalies and indicate particular surgical technics relative to the magnitude of functional and aesthetic repercussion. PMID- 1749617 TI - [The Tip Edge technic. Is it an advance in orthodontic concepts?]. AB - The originality of Tip Edge technique is due to the possibilities to take benefit both of the advantages of BEGG technique and Edgewise technique. With the differential anchorages, bite opening is more rapid and the correction of all the occlusal abnormalities is easy during stage I. During stage III the bracket Tip Edge with its original design permit a progressive torque, roots uprighting and an Edgewise finish. PMID- 1749618 TI - [Aging of the facial profile in the adult resting and balanced occlusion]. PMID- 1749619 TI - [Control of treatment and facial balance]. AB - Cephalometric analysis (made from the tracings of lateral head X-rays) participates to the orthodontic diagnosis. As it is done for each patient before and after treatment, the analysis allows for precision of the goals and for the control of their obtainance. Because therapeutic means have grown more and more precise, progress tracings during the active treatment are now considered very precious. They display teeth (and bones) good and bad displacement. They allow for mechanical activations, therapeutic decisions, and help for a better precision of the patient's cooperation. As the stability of the treated occlusion is the main goal, may be the post-treatment records (taken immediately after debanding) could be delayed for some months or even some years. PMID- 1749620 TI - ["Special" orthodontics to serve esthetics and function]. AB - Classical orthodontic approaches to bicuspid extractions in closed bite cases do not always reach the esthetic goal. To avoid worsening the profile concavity and undesired alterations in the nasolabial angle, incisor retraction must be discussed individually. We report third molar extraction cases with optimized changes in facial profiles. PMID- 1749621 TI - [Our testament in neuro-occlusal rehabilitation]. PMID- 1749622 TI - [High vaccination rates--only a question of information?]. PMID- 1749623 TI - [Therapeutic drugs, illicit poisons and environmental chemicals in breast milk- assessing the risk]. AB - Our knowledge about the transfer of drugs and environmental chemicals into breast milk has increased in the last years. This review is mainly based on recently published literature and focuses on all drugs and environmental substances with documented effects on lactation and the nursing infant. Our aim is to provide brief information for physicians who are counseling breastfeeding mothers. PMID- 1749624 TI - [Comparison of the classical Gibson-Cooke methods and the chloride-sensitive electrode in sweat testing for diagnosis of cystic fibrosis]. AB - In 43 children and adolescents (30 healthy and 13 CF patients) the Quantitative Pilocarpine Iontophoresis Test (QPIT) was compared with the ion-specific electrode. We found an excellent correlation between these two methods (r = 0.93) and no false positive or false negative results. With both procedures the total chloride-ion-concentration in sweat of healthy subjects and patients with CF differed significantly (p less than 0.001). Both, the original Gibson and Cooke sweat-test (QPIT) and the assessment of chloride with the sensitive electrode are highly reliable procedures for confirming the diagnosis of CF. PMID- 1749625 TI - [Delayed evaluation of test strips for blood glucose determination in small reflectometers]. AB - The precision and accuracy of reacted reagent strips (Haemoglucotest 20-800 R, Reflocheck) stored in an envelope and analysed 24 and 48 hours later, by means of glucose reflectance meters (Reflolux II, Reflocheck) was studied. A good correlation of the values estimated after 24 and 48 hours to the value analysed immediately after sampling was found for both systems (Reflolux II 24 hours later, r = 0.9713, y = 24.16 + 0.7369. x, and 48 hours later, r = 0.9388, y = 44.21 + 0.5234. x; Reflocheck 24 hours later, r = 0.977, y = 9.72 + 0.9525. x, and 48 hours later, r = 0.9433, y = 45.97 + 0.4802. x). Our data show, that the initial value can be calculated using the 24 and 48 hour values by means of linear regression. Therefore the analysis of reacted reagent strips for blood glucose determination is beneficial in the management of Typ-I-Diabetics. PMID- 1749626 TI - [Prenatal diagnosis and postnatal management of urologic abnormalities. Review and personal experiences]. AB - The possibilities and the difficulties of prenatal ultrasonography in detecting fetal renal abnormalities are discussed in this review article. The consequences of prenatally diagnosed uropathies are: intrauterine surgery, termination of pregnancy, induction of premature labour and an optimal preparation for the immediate postnatal diagnosis and management. PMID- 1749627 TI - [Polyvalent immunoglobulins in prevention of viral infections in children with neoplastic diseases treated with immunosuppressive therapy]. AB - 31 children with leukemias, lymphomas and solid tumors treated by polychemotherapy received prophylactic i.v. polyvalent immunoglobulins during 48 hours after exposion with varicella-zoster-virus, rubella-virus or mumps-virus. None of the 23 children with immunity against the exposed virus developed the infection. 8 children had no antibodies against the exposed virus. The prophylaxis with the polyvalent immunoglobulin protected them against chickenpox (6 children) and rubella (2 children). All children showed an elevation of the IgG level in plasma and the antibody titers against measles-, mumps-, rubella- and varicella-zoster-virus after application of the immunoglobulin. A study with a larger number of patients is necessary to confirm our results, that polyvalent immunoglobulins with high titers against exposed viruses are effective in prevention of this diseases in immunocompromised children. PMID- 1749628 TI - McKusick-Kaufman syndrome: report of the 66th case complicated by a staphyloma of the left eye. AB - Sixty-five cases of the Kaufman-McKusick syndrome, an autosomal recessive disorder, have been thus far reported in the literature. In the female, hydrometrocolpos and postaxial polydactyly are the prominent features of the disorder, and together with congenital heart disease form the distinctive triad of symptoms characterizing this entity. Since the initial reports, multiple other anomalies have been reported in the affected patients. Hydrometrocolpos, especially if unrecognized, may be a life-threatening condition in the newborn girl. We present a child with the features of the syndrome, and a staphyloma of the left eye, which necessitated its enucleation. PMID- 1749629 TI - [You make the diagnosis. Marshall syndrome]. PMID- 1749630 TI - [Rare indications for iron chelation therapy with desferrioxamine]. AB - In beta thalassaemia patients the subcutaneous desferrioxamine chelation therapy is performed routinely. Rare indications are hypoplastic anaemia, congenital dyserythropoetic anaemia and Fanconi anaemia. We initiated the chelation agent in three patients with the above mentioned diagnoses. The beginning of treatment in hypoplastic anaemia depends upon the quantity of red cell transfusions, whereas in dysterythropoetic anaemia the increased intestinal iron absorption has to be taken into consideration. Aim of the therapy is a negative iron balance. The evaluation of the iron balance is relatively simple. The girl with hypoplastic anaemia has been treated for 1.5 years. Within this time she received 11,680 mg iron by blood transfusions. The urinary iron output was 7112 mg. Depending on the analyzing method, the mean fecal iron excretion amounts 36.5% or 61% of the global excretion. Laboratory findings and clinical course are in favour to the aimed negative iron balance in two patients. PMID- 1749631 TI - [Vaccination against Haemophilus influenzae]. PMID- 1749632 TI - [The Austrian Scientific Prize for Pediatrics and Adolescent Medicine. An alternative method of financing research in pediatrics]. PMID- 1749633 TI - [Publications from Austrian pediatric institutions--analysis of the year 1989]. PMID- 1749634 TI - Is there such a thing as geriatric pain? PMID- 1749635 TI - Getting away from simple muscle contraction as a mechanism of tension-type headache. PMID- 1749636 TI - Clinical and pathophysiological observations in migraine and tension-type headache explained by integration of vascular, supraspinal and myofascial inputs. AB - A vascular-supraspinal-myogenic (VSM) model for pain in migraine based on our previous clinical and pathophysiological observations is proposed. According to the model, perceived pain (headache) intensity is determined by the sum of nociception from cephalic arteries and pericranial myofascial tissues converging upon the same neurons and integrated with supraspinal effects (usually facilitating). Vascular input predominates over myofascial input in migraine, whereas significance of supraspinal facilitation is difficult to estimate. The importance of these 3 effects may vary between patients and in the same individual with time. The model is in accordance with recent experimental studies showing convergence of somatovisceral afferents upon n. caudalis neurons. Also, long term potentiation due to nociceptive activation and sensitization of neurons to input from wider areas and non-nociceptive stimuli are relevant to our model. In tension-type headache, nociception is primarily myofascial, but vascular input cannot be disregarded. Supraspinal facilitation probably plays a large, sometimes dominant role (the MSV model). The model explains much of the complexity of the clinical picture of these disorders as well as their tendency to overlap and to change into one another. Also, a number of pathophysiological observations such as why muscles are tender during migraine, why trigger-point injection may cure migraine attacks and why chronic tension-type headache is often associated with episodes of pulsating pain, can be explained. The model gives a rational explanation of empirically developed, internationally accepted, multimodal treatment strategies for migraine and tension-type headache. It may thus serve a useful purpose in explaining the disorder to patients. Finally, the model points to several avenues of future research in animals and man. PMID- 1749637 TI - Differential effect of glucocorticoids on abdominal pain induced by morphine. AB - In patients with unexplained pain after cholecystectomy, morphine often induces pain and may increase plasma aspartate aminotransferase (AST) activity because of exaggerated or prolonged rises in pressure within the biliary system. These anomalous effects of morphine may be mediated by activation of autonomic or related afferent nuclei. In this study, 16 patients with pain and increases in AST after morphine were further studied after pre-treatment with dexamethasone and hydrocortisone. Pre-treatment with dexamethasone decreased scores for pain and nausea and prevented or attenuated increases in plasma AST and glucose; these effects were not observed after pre-treatment with hydrocortisone. Serial changes in plasma concentrations of catecholamines were determined in 8 patients and showed that pre-treatment with dexamethasone, but not hydrocortisone, was associated with lower concentrations of norepinephrine and epinephrine with overall reductions of 53% and 67%, respectively. These observations are consistent with a role for sympatho-adrenomedullary activation in abdominal pain induced by morphine. The different effects of dexamethasone and hydrocortisone raise the possibility that sympatho-adrenomedullary activation after morphine is influenced by the interaction of cortisol with type I glucocorticoid receptors which have a low affinity for dexamethasone and a high affinity for cortisol. PMID- 1749638 TI - Analyzing pain in rheumatoid arthritis patients. Pain coping strategies in patients who have had knee replacement surgery. AB - This study used the Coping Strategies Questionnaire (CSQ) to investigate pain coping strategies in 52 rheumatoid arthritis patients who reported having knee pain 1 year or more following knee replacement surgery. Data analysis revealed that, as a group, these patients were active copers in that they reported frequent use of a variety of pain coping strategies. Pain coping strategies were found to be related to measures of pain and adjustment. Patients who rated their ability to control and decrease pain high and who rarely engaged in catastrophizing (i.e., who scored high on the Pain Control and Rational Thinking factor of the CSQ) had much lower levels of pain and psychological disability than patients who did not. Coping strategies were not found to relate to age, gender, obesity status or disability/compensation status. Taken together, these results suggest that an analysis of pain coping strategies may be helpful in understanding pain in arthritis patients who have pain following joint replacement surgery. PMID- 1749639 TI - Does the sympathetic block outlast sensory block: a thermographic evaluation. AB - A study to evaluate the duration of sympathetic and sensory block in the L2 and L5 dermatome distributions using thermography and pinprick was conducted. Twenty patients received epidural block using 2% lidocaine with epinephrine. Onset and duration of the sensory and sympathetic blocks were determined and compared statistically. There was no difference between the duration of sensory and sympathetic block over the L2 dermatome, but sympathetic block was significantly longer than sensory block in the L5 dermatome. This study demonstrates that the duration of sympathetic block can be either longer or shorter than sensory block in L2 and L5 dermatomes. This has important implications for interpretation of results of differential epidural studies in that one cannot predict the duration of sympathetic block based on duration of sensory block. PMID- 1749640 TI - Depression and the chronic pain experience. AB - The present study examined the relationship between depression and a constellation of pain-related variables that describe the experience of chronic pain patients. Thirty-seven depressed and 32 non-depressed heterogeneous chronic pain patients were identified through structured interviews, use of standardized criteria and scores on the Beck Depression Inventory (BDI). The 2 groups were compared on demographic variables and scores on the Marlowe-Crowne Social Desirability scale (MC), as well as measures of disability and medication use, pain severity, interference due to pain and reported pain behaviors. The depressed group was found to be younger and to score lower on the MC than the non depressed group. Multivariate analyses of covariance (MANCOVA), using age and MC as covariates, revealed that depressed chronic pain patients, relative to their non-depressed counterparts, reported greater pain intensity, greater interference due to pain and more pain behaviors. There were no group differences on the measures of disability and use of medications. The results provide further support for the importance of incorporating depression into clinical and theoretical formulations of chronic pain. Future use of structured interviews and standardized criteria for diagnosing depression may clarify some of the inconsistencies found in the literature. PMID- 1749641 TI - Pain beliefs and the use of cognitive-behavioral coping strategies. AB - Patients' beliefs about chronic pain, such as how long it will last and whether it is a mysterious experience, have been shown to be related to compliance with treatment programs. The present study examined whether these pain beliefs related to a specific component of pain management, namely the frequency of use and the perceived effectiveness of cognitive and behavioral coping strategies. One hundred twenty chronic pain patients were administered the Pain Beliefs and Perceptions inventory (PBAPI) and the Coping Strategies questionnaire (CSQ). A cluster analysis of 2 pain beliefs (that pain is enduring and that pain is mysterious) was conducted revealing 3 distinct subgroups of patients based upon these 2 beliefs. Multivariate analysis of variance was used to detect whether the use of cognitive-behavioral pain coping strategies differed in patients in the 3 pain beliefs subgroups. The results indicated that patients belonging to the group characterized by the belief that pain was enduring and mysterious were less likely to use cognitive coping strategies (e.g., reinterpretation of pain sensation), more likely to catastrophize, and less likely to rate their coping strategies as effective in controlling and decreasing pain than patients believing their pain to be understandable and of short duration. The implications of these results for understanding the patient's choice of and compliance with treatment and coping efforts is discussed. PMID- 1749642 TI - A possible indicator of functional pain: poor pain scale correlation. AB - We studied correlations of pain measures in patients with either inflammatory bowel disease (IBD), a disease with a clear organic cause, or irritable bowel syndrome (IBS), a functional pain syndrome in which there is little demonstrable pathology. Correlations were determined between measures on the visual analogue scale (VAS) and on the McGill Pain Questionnaire (MPQ). The VAS score and present pain intensity scale (PPI) of the MPQ correlated well in the organic IBD but correlated poorly in the functional IBS. Differences in correlation between the VAS and PPI scores in functional versus organic disease did not appear to be due to altered sensory and affective pain components. This finding is similar to what we observed in our previous study of organic and functional pain syndromes in the musculoskeletal system. Correlations between the other measures are also discussed. PMID- 1749643 TI - The prognosis with postherpetic neuralgia. AB - One hundred and fifty-six patients with moderate to severe postherpetic neuralgia (PHN) were followed for up to 11 years. Nearly half of all patients were doing well at the final assessment (median 2 years) and more than half of these were on no therapy at this time. The most commonly used agents associated with a good outcome were antidepressants, topical capsaicin and analgesics of various kinds. Longer duration PHN appeared to have a worse prognosis. More of these patients were noted to be using some form of treatment at follow up. A group of patients seemed to follow a progressive course and were refractory to all treatments used in this study. PMID- 1749644 TI - Discharge behaviour of feline gamma-motoneurones following induction of an artificial myositis. AB - The study was undertaken to test the widely held hypothesis that a painful lesion of the skeleto-motor system leads to an increase in the neuromuscular component of muscle tone by activating gamma-motoneurones in the affected region. In chloralose-anaesthetized cats, artificial myositis was induced in the lateral gastrocnemius-soleus (LGS) muscle and several hours later the impulse activity was recorded from single gamma-motoaxons supplying the medial gastrocnemius (MG) muscle. Under the conditions of the study, the majority of the fusimotor neurones had a resting activity and could be readily excited by natural stimuli. In contrast to the assumptions of the working hypothesis, the gamma-motoneurones in the myositis animals were not activated but showed a strong inhibition; both resting activity and excitability by electrical and natural stimuli were decreased. Additional recordings from fusimotor neurones of a flexor muscle (tibialis anterior, TA) demonstrated that in the preparation used, the behaviour of the flexor gamma-motoneurones was different from extensor ones in that the former usually had no resting activity and did not respond to natural stimuli. The only discernible effect of a myositis of the LGS muscle on the TA gamma motoneurones was a decrease in their electrical reflex threshold. The results of the study do not support the assumption that a painful muscle lesion is followed by an activation of the gamma-loop that leads to an increase in muscle tone. Instead, the data may offer an explanation for the weakness and--in chronic cases -the reflex atrophy of lesioned muscles. PMID- 1749645 TI - The threshold for the depressive effect of intrathecal morphine on the spinal nociceptive flexor reflex is increased during autotomy after sciatic nerve section in rats. AB - The effect of intrathecal (i.t.) morphine on the spinal nociceptive flexor reflex in doses ranging between 10 ng and 10 micrograms was studied in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves or in rats in which the sciatic nerve had been unilaterally sectioned. In rats with intact nerves the initial effect of i.t. morphine on the flexor reflex was a brief facilitation followed by depression. The threshold dose of morphine for reflex depression was 100 ng. In animals which did not develop autotomy after nerve section or in which autotomy had ceased for several days prior to the acute experiments, i.t. morphine had a similar depressive effect on the flexor reflex as in animals with intact nerves. However, in rats which were autotomizing at the time of the acute experiment, the threshold dose of the depressive effect of morphine was increased 3-5 fold. With higher doses of morphine (1-3 micrograms), similar depression of the reflex was found in all groups. The present results revealed a decreased sensitivity of spinal reflex mechanisms to low, but not high, doses of morphine after sciatic nerve section accompanied by autotomy. Nerve section per se did not alter opioid sensitivity. Thus, decreased effectiveness of morphine in this model for neuropathic pain may be partially due to a desensitization to the analgesic action of opioids in the spinal cord. Since after sciatic nerve section there is a differential sensitivity to the antinociceptive effect of i.t. morphine between autotomizing and non-autotomizing rats, it is further suggested that autotomy after peripheral nerve section in rats is a useful model for the study of neuropathic pain. PMID- 1749646 TI - Pain in chronic pancreatitis. PMID- 1749647 TI - On "The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy" by Bach et al. in Pain, 40 (1990) 29-34. PMID- 1749648 TI - An additional perspective on the Fordyce/Schmidt controversy. PMID- 1749649 TI - On 'Spinal cord stimulation for chronic, intractable pain: superiority of 'multi channel' devices' by North et al., in Pain (1991) 119-130. PMID- 1749650 TI - Stable and unstable fractures of the femoral shaft. AB - A retrospective review of 99 cases of stable and unstable femoral shaft fractures treated with Grosse-Kempf intramedullary fixation is presented. Despite minor complications and technical problems, the procedures resulted in union with acceptable alignment in 98% of cases. Details of the complications and technical problems are reviewed. There was no incidence of deep infection despite 16 open fractures. The two cases of nonunion were salvaged with revision internal fixation and bone grafting. Grosse-Kempf interlocking intramedullary fixation is a technically demanding procedure, but offers excellent results in the management of stable and unstable, open and closed fractures of the femoral shaft. PMID- 1749651 TI - Traumatic axial-ulnar disruption of the carpus. AB - Six men and two women (aged 37 to 50) with traumatic axial-ulnar disruption of the carpus were evaluated at an average of 34 months following treatment. The injuries were caused by a broad, anteroposterior crushing force to the hand and wrist resulting from, in most cases, an industrial accident. Our treatment began 2 weeks postinjury in five patients and more than 1 month postinjury in three patients. Treatment techniques included closed or open reduction and plaster immobilization, primary or delayed skin grafting, immediate revascularization, and secondary techniques. Cooney's criteria rated treatment results as excellent in one patient, good in two, fair in two, and poor in three. Although four variations of this injury were identified, the pattern of disruption appeared to have no influence on the results. An early surgical procedure seems to be most effective. PMID- 1749652 TI - Reflex sympathetic dystrophy of the patellofemoral joint. AB - Eighteen patients with a diagnosis of reflex sympathetic dystrophy (RSD) affecting the knee were reviewed. Minor isolated injuries and operations about the knee triggered the original episode. The symptoms, regardless of location and mechanism of injury, occurred in the patellofemoral joint. Roentgenographic features of patchy demineralization and abnormal uptake on a 99mTc scan were typically located in the patella and corresponding femoral articular surface. At the initial stage of the syndrome, pain, hypersensitivity to touch, and inhibition of the quadriceps muscle were the most prominent features. In the later stages of the syndrome, functional instability due to quadriceps weakness created dependence on a knee brace or crutch support. Six patients whose RSD was initially misdiagnosed underwent numerous unsuccessful surgical procedures. In three of these patients, the knee was ultimately fused. All patients had an initial isolated knee injury (usually after minor trauma), and prolonged periods of immobilization and a cast, and 12 of the 18 patients were involved with workers' compensation. Early diagnosis and prompt treatment with an epidural block, followed by intensive physiotherapy, are recommended. A personal doctor/patient relationship that offers guidance and encouragement is key to successful management of this syndrome. PMID- 1749653 TI - Intraosseous ganglia of the carpal bones. AB - Intraosseous ganglia are benign, cystic lesions of bone that are most commonly found in the subchondral region of long bones of the lower extremity. Reports of isolated carpal involvement are rare; however, it has been well documented that these lesions may produce chronic wrist pain. Various theories of pathogenesis have been advanced, including synovial herniation, mucoid degeneration, primary cellular metaplasia, and chronic repetitive trauma. In our study, 11 patients (seven female, four male) with 12 lesions were treated for chronic wrist pain associated with intraosseous carpal ganglia. All patients had similar complaints preoperatively and were unable to obtain relief with rest, immobilization, or nonsteroidal medication. Aside from local tenderness over the involved bone, the physical examination was unremarkable. Acute trauma was not found to be a factor in any of these patients' histories. Eleven lesions in 10 patients were grafted with bone from the distal radius. A complete resolution of symptoms was seen at a 20-month follow-up examination. PMID- 1749654 TI - Arthroscopic treatment of septic arthritic knees in children and adolescents. AB - Septic arthritis of the hip and knee is very common in children and adolescents. Sixteen consecutive patients were treated for septic arthritis of the kee with arthroscopic lavage and debridement. Ten of the 16 knees were culture positive on preoperative aspiration. The average duration of antibiotic treatment was 19 days. The mean immobilization period was 1 1/2 days and the time to full and painless range of motion averaged 2.8 weeks. All patients resumed normal activities by 3 weeks, no infections recurred, and postoperative morbidity was minimal. PMID- 1749655 TI - Works in progress #7. Clinical experience with the Accu-Path threaded acetabular cup. A preliminary report. AB - Clinical experience with the Accu-Path threaded titanium hemispheric cup is presented. A series of 62 cases was followed for an average of 28.1 months (range, 6 to 48). Primary surgery was performed in 50 cases and revision surgery in 12. The surgical technique is described in detail. Preoperative Harris scores improved from 28 to 93 in primary cases and from 24 to 84 in revision cases. Complications included 3.2% dislocation, 3.2% loss of cup position, and 1.6% recurrent subluxation. The overall reoperation rate was 8% (8% in primary surgery and 8.3% in revision surgery). Roentgenographic analysis is discussed. The importance of preservation of the subchondral plate and a rim fit in the use of this implant is stressed. It is not indicated in those with loss of the plate due either to prior surgery (as in revision) or in aggressive over-reaming in primary cases. Although the overall results were encouraging, caution was recommended- especially in revision surgery or in the patient with severe osteopenia. PMID- 1749656 TI - Tips of the trade #40. Removal of a fractured intramedullary nail. PMID- 1749657 TI - Growing pains. PMID- 1749658 TI - Imaging rounds #109. Intraosseous ganglia of the scaphoid. AB - An intraosseous ganglion is a relatively uncommon, benign, cyst-like lesion that occurs in middle-aged adults, and has a predilection for the tibia. Roentgenographically, it commonly appears as well a well-defined osteolytic lesion with a surrounding area of sclerosis. PMID- 1749659 TI - Tips of the trade #41. Modified coaptation splint for humeral shaft fractures. AB - A technique for applying a modified coaptation splint for humeral shaft fractures is presented. Using this method, the splint extends from the base of the neck, passes over the shoulder and along the front and back of the arm, and returns toward the axillary fold. To prevent slippage, the proximal end of the splint is secured to the chest with a strap. PMID- 1749660 TI - Recurrent dislocation of the proximal tibiofibular joint. AB - Recurrent dislocation of the proximal tibiofibular joint is a rare injury. This report presents a case of bilateral recurrent dislocations of the proximal tibiofibular joint in a jet skier that responded to physical therapy and activity modification. A review of the literature is provided, with attention to the mechanism of injury and other treatment options--including arthrodesis and resection of the proximal fibula. This diagnosis should be considered in jet skiers with lateral-sided knee pain. PMID- 1749661 TI - Operative management of distal femoral fractures. AB - Fractures of the distal femur can be managed successfully with surgery. A good result depends on identification of all fragments, adequate repair of soft tissue, appropriate bone grafting, meticulous intrafragmentary compression, and complete reduction of the joint space. Instrumentation may include condylar blade plates, condylar screws, or locked intramedullary rods. Anatomic reconstruction with stable fixation permits early rehabilitation and recovery of full function after fracture. PMID- 1749662 TI - Isolated dislocation of the radial head. AB - Fifty-four patients (12 bilateral) with isolated dislocations of the radial head were encountered over a 20-year period. The congenital varieties (26 patients) included isolated unilateral, familial, synostosis-related, and syndrome-related. The acquired types (28 patients) involved trauma, neuromuscular impairment, or adaptive dislodgments. Acute, traumatic dislocation (17 patients) was the most common presentation. Others were diagnosed incidentally, or associated with discomfort, dysfunction, or deformity. Closed reduction of an acute traumatic dislocation was generally successful (16 of 17 patients). Realignment attempts (three cases) on late diagnosed traumatic cases and isolated congenital types were invariably unsuccessful, eventually requiring radial head excision. Four patients underwent excision of the head of the radius as primary treatment. PMID- 1749663 TI - Hematoma block of distal forearm fractures. Is it safe? AB - Fractures of the distal radius and ulna are common, and methods of obtaining pain relief prior to their reduction include general anesthesia, intravenous regional anesthesia, and local infiltration of the fracture hematoma (hematoma block). A prospective study of 132 distal forearm fractures treated with hematoma block was undertaken. This group was compared with a control group of 100 patients who had had either general anesthesia or intravenous regional anesthesia. Results revealed no incidence of infection in either group. If appropriate precautions are taken, hematoma block does not increase the risk of infection. PMID- 1749664 TI - Survey of health care available to child athletes. AB - Surveys were sent to 84 children's hospitals and 397 sportsmedicine clinics to characterize the care available for the child athlete (aged 4 to 12 years); they were completed by 209 facilities (43% response rate). Fourteen of the facilities had a sportsmedicine clinic specifically for children; care was available for the child athlete in an additional 46 facilities, but less than 10% of the clinic visits were made by athletes aged 4 to 12 years. All responding clinics were further characterized by location, length of operation, composition, referral base, profitability and funding, etc. Although there are few sportsmedicine clinics specifically for children, many facilities provide experienced personnel in existing clinics to care for young athletes. PMID- 1749665 TI - Low-velocity knee dislocation. AB - Complete knee dislocation is an uncommon but potentially devastating injury with a reported high rate of neurovascular injury. Treatment of this ligamentous injury is controversial. The operative (repair of all ligaments) and nonoperative management of ligament injuries appears to result in a stiff knee (decreased range of motion [ROM]), and/or a significant incidence of clinical instability and pain. We report our data on low-velocity knee dislocations and present a treatment plan of noninvasive assessment of the vascular status, a stabilizing procedure centered on posterior cruciate ligament reconstruction (PCL) and an aggressive rehabilitation program that can result in improved ROM, acceptable stability, and a more optimal functional outcome. PMID- 1749666 TI - Imaging considerations of central nervous system manifestations in pediatric patients with neurofibromatosis type 1. AB - CT and MRI were used in a prospective study of the central nervous system (CNS) manifestations in 41 consecutive children with neurofibromatosis type 1 (NF-1). Gadolinium-DTPA was used in 15 patients. MRI was more effective than CT in delimiting the extension of the optic pathway glioma and in evaluating associated cerebral malformations. MRI visualized lesions generally undetected by CT, in the form of iso- or hyperintense foci with respect to the cerebral cortex in T2 weighted sequences. Well-delimited lesions of high signal intensity were observed in the globus pallidus (22 cases), the internal capsule (6 cases), corpus callosum (2 cases), anterior commissure (1 case) and semioval center (2 cases). Poorly defined hyper- or isointense areas were also observed affecting the cerebellar white matter (21 cases) and brain stem (17 cases). None of these lesions showed Gadolinium-DTPA enhancement, and were of no clinical significance. MRI has displaced CT in the initial diagnosis of patients with NF-1. Periodic annual MRI controls are only justified in patients with MRI changes to evaluate the progression or stabilization of the lesions. PMID- 1749667 TI - Cerebral-blood-flow-velocity measurements in neonates: technique and interobserver reliability. AB - The interobserver reliability for absolute cerebral-blood-flow-velocity measurements by colour and duplex Doppler sonography was tested in 32 neonates with a mean birth weight of 1489 (SD 644) g, and a gestational age of 29.9 (SD 3.5) weeks. Using standardized technique, two observers recorded on videotape, the Doppler spectrum of the anterior cerebral artery, the intracranial internal carotid artery and the middle cerebral artery. Peak systolic flow, end diastolic flow, mean flow velocity, resistive index and pulsatility index were computed from 3 consecutive waveforms by each observer. The estimates of interobserver reliability using the intraclass correlation coefficient of the examiners varied from 0.95 to 1.00. Therefore, cerebral blood flow velocity can be reliably measured in premature infants. PMID- 1749668 TI - Neurosonographic abnormalities in chromosomal disorders. AB - A retrospective study of cranial sonograms in infants with autosomal trisomies excluding Down's syndrome was performed. A range of abnormalities was found including structural anomalies, vascular changes and hydrocephalus. Although nonspecific, many of these abnormalities can suggest a specific chromosomal abnormality in the appropriate clinical setting. PMID- 1749669 TI - Cervical lymphadenitis complicated by mycotic carotid artery aneurysm. AB - A case of mycotic carotid artery aneurysm due to cervical lymphadenitis in a four year old child is presented. Sonography and computed tomography (CT) demonstrated an irregular fluid-containing neck mass, similar in appearance to an uncomplicated abscess. Continuity with the carotid artery was suggested on sonography, and CT demonstrated intense contrast enhancement of the liquid portion of the mass. Mycotic carotid artery aneurysm is a rare, but potentially fatal, complication of cervical lymphadenitis that is detectable with noninvasive diagnostic imaging studies. PMID- 1749670 TI - Pulmonary changes in congenital syphilis. AB - Three of seven infants afflicted with congenital syphilis at our institution in the past five years showed diffuse pulmonary infiltrates. These persisted long after adequate antibiotic treatment of the primary infection. Review of pathologic literature suggests these infiltrates represent pulmonary immaturity, extramedullary hematopoiesis, and interstitial scarring. PMID- 1749671 TI - Esophageal foreign bodies in children with vascular ring or aberrant right subclavian artery: coincidence or causation? AB - This is the report of 4 children, 2 with a vascular ring and 2 with an aberrant right subclavian artery, who presented with an esophageal foreign body in the proximal esophagus above the level of the vascular anomaly. A deep erosion of the esophagus at the site of the foreign body was demonstrated in 2 patients. PMID- 1749672 TI - Esophageal diverticula in childhood associated with strictures from unsuspected foreign bodies of the esophagus. AB - Two pediatric patients are presented with progressive dysphagia due to esophageal strictures secondary to unrecognized foreign bodies. Diverticula were present above the strictures. PMID- 1749673 TI - Salt losing nephropathy simulating congenital adrenal hyperplasia in infants with obstructive uropathy and/or vesicoureteral reflux--value of ultrasonography in diagnosis. AB - Salt losing nephropathy, occurring predominantly in male infants, has been reported in association with a spectrum of urologic diseases including obstructive uropathy and massive, infected vesicoureteral reflux (VUR). This has been called pseudo-hypoaldosteronism (PHA) or alternatively, pseudo salt-losing congenital adrenal hyperplasia (CAH), and is thought to reflect a tubular unresponsiveness to aldosterone. We report our experience with six cases, discuss one case in detail and review the 39 cases previously reported. A one month old male infant presented with a left upper quadrant mass. Signs and symptoms included vomiting, dehydration, hyponatremia and hyperkalemia. This suggested the diagnosis of CAH for which therapy was instituted. Ultrasonographic examination subsequently revealed the mass to be a urinoma in an infant with posterior urethral valve (PUV) and obstructive hydronephrosis. PMID- 1749674 TI - RARE-MR-urography in the diagnosis of upper urinary tract abnormalities in children. AB - RARE-MR-urography (Rapid Acquisition with Relaxation Enhancement) is a fast MR imaging technique (6.4 s/acquisition) that selectively depicts fluid by heavy T2 weighting. From 9/1989 to 11/1990, RARE-MR urograms were prospectively evaluated in the diagnosis of upper urinary tract abnormalities in 55 children. The method is performed in several planes and combined with a coronal, T1-weighted spin-echo sequence. Forty out of 42 kidneys with dilated renal pelvis, and 21 out of 24 dilated ureters were identified, only the mildly dilated ones were missed. Even in non-functioning kidneys the urinary tract was clearly depicted by RARE-MR urography. However, no differentiation could be made with this technique between vesicoureteral reflux and non-refluxing dilatation of ureter and/or renal pelvis. All 19 pelviureteric obstructions and all eight renal duplications with a dilated segment were identified. RARE-MR-urography is a new tool for diagnosing urinary tract abnormalities in children without having to employ ionizing radiation, contrast media, or general anesthesia. A dilated urinary tract can be shown in one image displaying the entire urinary system, similar to excretory urography. The technique is presently not able to provide the information of voiding cystourethrography or renal scintigraphy, nor is it as easy to perform as ultrasound. However, in certain cases it may replace excretory urography. PMID- 1749675 TI - Perinatal lethal hypophosphatasia; clinical, radiologic and morphologic findings. AB - Clinical, radiographic and morphologic analysis of nineteen cases of perinatal (lethal) hypophosphatasia was performed. Three families each had two affected offspring. All of the patients had lethal short limb dwarfism with very soft calvaria. Other clinical findings included polyhydramnios, blue sclerae and spurs in the mid-portion of the forearms and lower legs. Considerable variability was found in the skeletal radiographs. In addition to the well known radiographic features such as generalized decrease in the size of ossified bones with some bones not ossified at all, other changes observed included: 1) marked variability in the amount of bone ossification; 2) variability between patients as to which bones were most severely affected; 3) unusually dense, round, flattened, butterfly shaped; and sagittally clefted vertebral bodies; 4) variability in femoral shape including "chromosome" like, "campomelic" like, and shortening with or without metaphyseal cupping or irregularities; 5) osteochondral projections (Bowdler spurs) of the midshaft of the fibula and ulna. Recognition of the marked clinical and radiographic variability in this autosomal recessive lethal skeletal dysplasia is important for accurate genetic counseling and prenatal diagnosis. PMID- 1749676 TI - Kabuki make-up (Niikawa-Kuroki) syndrome: clinical and radiological observations in two Sicilian children. AB - The Authors describe two patients aged 5 and 8, a female and a male, affected by a condition of polymalformations known as Kabuki make-up or Niikawa-Kuroki syndrome, having a neonatal incidence of 1:32,000 in Japan. There are two hypothesis about the apparent rarity of the syndrome in the rest of the world, including the Asian Continent: the first is that it exists, but is infrequently recognized outside Japan and the second is that it is really more frequent in those parts of the world, where ethnic exchanges are uncommon, as it happens in Japan. PMID- 1749677 TI - Tuberous sclerosis complex: oligosymptomatic variant associated with subependymal giant-cell astrocytoma. PMID- 1749678 TI - Rectal diverticulum in an infant. AB - The occurrence of rectal diverticula are rare. They are invariably accompanied by colonic diverticulosis, especially the sigmoid segment. To our knowledge, this condition has not been previously detected during childhood, and the youngest patient reported was 18 years old. In this report we present a solitary rectal diverticulum in a 25-day-old infant without accompanying colonic diverticula. The existence of rectal diverticulum in this infant convincingly suggests a congenital etiology. PMID- 1749679 TI - Primary lymphoma of brain in childhood. AB - Primary brain lymphoma is exceedingly rare during the first decade of life. We report an unusual case, not only being one of the youngest presented, but also because of the unusual CT features exhibited. PMID- 1749680 TI - Normal size left ventricle on antenatal scan in lethal hypoplastic left heart syndrome. AB - We present a case of lethal hypoplastic left heart syndrome missed at routine 20 week antenatal ultrasound examination because the left ventricle was of normal size on the standard four-chamber cardiac view. Hypoplastic left heart syndrome includes a spectrum of cardiac malformations. This case illustrates the difficulty in excluding the diagnosis of hypoplastic left heart syndrome on a single view from one antenatal second-trimester ultrasound examination. PMID- 1749681 TI - Infected teratoma of lower posterior mediastinum in a six-year-old boy. AB - A six-year old boy presented with prolonged unexplained fever caused by an infected teratoma of the lower posterior mediastinum. Modern imaging, combining ultrasonography with computed tomography, enabled the correct diagnosis of topography, extension and nature of this rare lesion to be made and explained the clinical features. Follow-up CT showed regression of the abscess after antibiotics thus permitting elective surgery. PMID- 1749682 TI - Left-sided posterior mediastinal thymus--MRI findings. AB - Anomalous descent of the thymus may result in ectopic thymic tissue in the neck and/or the mediastinum and can mimic an abnormal mediastinal mass. We present one case of a "posterior mediastinal mass" that was diagnosed as a posterior mediastinal thymus utilizing CT plus MRI. PMID- 1749683 TI - Torsion of a wandering spleen in a one month old, with a confusing ultrasound examination. AB - Torsion of a wandering spleen is an uncommon diagnosis and rare in children. The entity is commonly misdiagnosed. In our case, a one month old infant presented with an abdominal mass. Ultrasound identified a large heterogeneous mass but also revealed what appeared to be normal splenic tissue below the left hemidiaphragm. The ultrasound findings steered us away from the diagnosis of wandering spleen or splenic infarction. Differential diagnosis of the mass included twisted hemorrhagic ovarian cyst, neoplastic mass, or inflammatory abscess. Postoperative histologic analysis demonstrated splenic infarction. PMID- 1749684 TI - Plasma cell granuloma presenting as an iliopsoas mass--mimicking a rhabdomyosarcoma. AB - Plasma cell granuloma is a rare benign tumour that can affect people of all ages. These are most commonly found in the lung but have been reported in numerous extrapulmonary sites. By gross and radiographic appearance they can mimic malignancies. We report a case of a plasma cell granuloma arising in the right pelvis contiguous with the iliopsoas mimicking a sarcoma. PMID- 1749685 TI - Chondroosseous dysplasia in severe combined immunodeficiency due to adenosine deaminase deficiency (chondroosseous dysplasia in ADA deficiency SCID). AB - Adenosine deaminase (ADA) deficiency may manifest as severe combined immunodeficiency (SCID) in early infancy. Some of these children develop radiologic changes which may be in part related to effects of this enzyme deficiency on the bony epiphysis. We describe the radiologic changes in a neonate with ADA deficiency and their resolution with polyethylene glycol conjugated adenosine deaminase (PEG-ADA, ADAGEN: Enzon, Inc., South Plainfield, NJ) enzyme replacement therapy. PMID- 1749686 TI - Congenital ossifying fibroma (osteofibrous dysplasia) of the tibia--a case report. AB - Ossifying fibromas of the long bones of the leg are benign lesions occurring in the pediatric age group identical in histological appearance to the similarly named tumor of the jaw in adults. Most frequently presentation occurs after minor trauma with symptoms of a swelling of the tibia or fibula which may be painful. Pathological fracture or limp are also occasional presentations. Congenital cases are extremely rare. We describe an otherwise normal male neonate who presented at birth with a bowed right lower leg. The limb was 1 cm shorter than the other side, with tibia vara and a firm mass situated anteriorly. X-ray showed a mixed lytic and sclerotic lesion in the proximal metaphysis of the tibia. Biopsy showed collagenous stroma containing spindle cells and irregular trabeculae of woven bone rimmed by plump osteoblasts. As the appearances were typical of an ossifying fibroma (osteofibrous dysplasia) no surgical treatment was given. The patient was well with no growth of the tumor and with radiological evidence of healing at 1 year follow up. This case is presented to draw attention to the clinicopathological features of this unusual lesion which must be considered in the differential diagnosis of congenital lesions of the tibia. PMID- 1749687 TI - Simultaneous (synchronous) occurrence of Ewing sarcoma. AB - A case of Ewing sarcoma in a girl 13 year-old with multiple bone and soft tissue lesions at the time of diagnosis is presented. The lungs were free from the disease. This patient represents most likely a simultaneous (synchronous) Ewing sarcoma. PMID- 1749688 TI - Multifocal chronic osteomyelitis with exuberant periosteal formation. AB - A very protracted unusual course of multifocal osteomyelitis in a young child is presented. Initial radiolucencies were followed by a marked periosteal overgrowth, which resulted in severe bone deformities. A viral etiology is suggested. PMID- 1749689 TI - Maple tree knee: a unique foreign body--value of ultrasound and CT examination. AB - This report describes an intraosseous maple branch fragment which presented on initial radiographs as a benign appearing lytic bone lesion. Sonography and CT confirmed the presence of intraosseous and intra-articular foreign body and chronic foreign body reaction. PMID- 1749690 TI - Management of the febrile child: a survey of pediatric and emergency medicine residency directors. AB - We conducted a survey to determine whether there is uniformity in the training of residents regarding the management of febrile children. One hundred forty-three (62%) of 231 pediatric and 39 (53%) of the 73 emergency medicine residency directors responded. There was no uniformity in the definition of a fever. Ninety nine percent of the pediatric and 82% of the emergency medicine residency directors teach that all febrile infants less than 4 weeks of age should be hospitalized (P less than 0.0001). Forty-six percent of residency directors teach that a lumbar puncture should be performed for all children less than 12 months of age with their first febrile convulsion. Thirty percent of pediatric and 62% of emergency medicine residency directors teach that a blood culture should be obtained from a child with fever without source who is younger than 24 months of age (P less than 0.0005). Nonspecific tests are taught to be used to determine which febrile child should have a blood culture as follows: white blood cell count, 50%; differential, 20%; erythrocyte sedimentation rate, 13%; and C reactive protein, 2%. There was little uniformity of teaching regarding the approach to the febrile child and there were significant differences in training by specialty. PMID- 1749691 TI - The changing spectrum of group B streptococcal disease in infants: an eleven-year experience in a tertiary care hospital. AB - Risk factors, clinical syndromes and the case-fatality rates associated with Group B Streptococcus (GBS) infections in infants managed at the University of Rochester Medical Center during 1979 to 1989 were reviewed. Overall 92 episodes of early onset disease (EOD) and 54 of late onset disease (LOD) were diagnosed in 143 infants (3 infants with EOD presented later with LOD). About one-third of patients with EOD and controls were non-white compared with two-thirds of patients with LOD that occurred in racial minority groups. Prematurity and low birth weight were significantly more common in patients with invasive GBS disease than in controls. Eighty-three of 92 (90%) cases of EOD were detected during the first day of life and 10 of 54 (19%) cases of LOD occurred in infants older than 3 months of age. At the time of diagnosis 4% of infants with EOD were asymptomatic, 54% had respiratory disease, 27% had sepsis without a focus, 15% had meningitis and 1% had urinary tract infection or omphalitis. Among infants with LOD 46% had sepsis, 37% meningitis, 7% urinary tract infection, 6% osteomyelitis and/or septic arthritis and 4% cellulitis or pneumonia. Leukopenia and shift to the left were observed in 43 and 61% of episodes of EOD and in 28 and 57% of episodes of LOD, respectively. All infants were promptly treated with antibiotics and vigorous supportive therapy. The case-fatality rate was 13% in EOD and 0 in LOD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1749692 TI - Characteristics and outcome of acute infection with hepatitis B virus in children with cancer. AB - After an outbreak of hepatitis B virus (HBV) infection in a unit of pediatric oncology, the clinical outcome and HBV markers were followed in 1 child with chronic and 10 children with acute HBV infection for 12 months. Four children had acute hepatitis with jaundice whereas 7 of the infections were subclinical. Ten children had antecedent malignancies and 1 had aplastic anemia. Four patients died of causes unrelated to the hepatitis after periods of 2, 4, 8 and 10 months. All 3 children who were not immunosuppressed at the time of contracting the HBV infection quickly turned negative for hepatitis B surface antigen (HBsAg), whereas only 2 of 8 patients who were immunosuppressed by chemotherapy eventually became HBsAg-negative. The latter 8 patients were also hepatitis B e antigen (HBeAg)-positive. Two of them quickly cleared HBeAg, but 6 remained HBeAg positive throughout the follow-up. In 6 of 9 patients HBsAg was also detected in saliva. These results suggest that children who are receiving anticancer chemotherapy have an increased risk of remaining HBeAg-positive and secreting HBsAg and possibly HBV in their saliva, which makes them particularly infective. PMID- 1749693 TI - Immunologic study of the asplenia syndrome. AB - Asplenia syndrome is usually associated with complex congenital cardiovascular defects. These patients often succumb to overwhelming infections. A complete immunological evaluation was therefore conducted on 13 consecutive patients with asplenia syndrome and 12 age-matched patients with congenital heart disease but without evident splenic problems. IgG, IgA, IgM and C3 and C4 values were normal for age in all subjects studied. T cell subsets, including the percentage of CD3, and CD4 cells and the CD4/CD8 ratio were significantly different in patients and controls (P less than 0.01, respectively). Lymphoproliferative responses to mitogens (ConA, concanavalin A, phytohemagglutinin and pokeweed mitogen) were also decreased in patients. Fc-mediated clearance of sensitized autologous erythrocytes was significantly impaired in patients (n = 13) when compared with age-matched controls (n = 5) (clearance t1/2 59.0 +/- 9.6 minutes vs. 12.5 +/- 1.6 minutes, P less than 0.001). Thus profoundly impaired reticuloendothelial clearance and decreased T cell function might account for the life-threatening infections frequently seen in patients with congenital asplenia syndrome. PMID- 1749694 TI - Ureaplasma urealyticum demonstrated by open lung biopsy in newborns with chronic lung disease. AB - Lung biopsy tissue from eight infants with chronic lung disease was evaluated for the presence of Ureaplasma urealyticum. Specimens from four infants grew the organism. Pleural fluid cultures matched lung tissue but tracheal cultures were negative in two babies with positive lung tissue. There were no distinguishing pathologic findings in the four culture-positive infants which could be used to identify them vs. the culture-negative infants. Three culture-positive infants improved clinically after therapy directed at Ureaplasma even though two remained culture-positive. Ureaplasma grows in lung tissue of infants with chronic lung disease, it does not demonstrate any specific standard pathologic findings and tissue cultures do not match endotracheal cultures. PMID- 1749695 TI - Stability of isoniazid, rifampin and pyrazinamide in suspensions used for the treatment of tuberculosis in children. AB - The stability of monosuspensions, cosuspensions and multisuspensions of isoniazid (INH), pyrazinamide (PZA) and rifampin (RIF) has been evaluated by high pressure liquid chromatography over a period of 28 days both with and without the addition of vitamin C (20 micrograms/ml) and at ambient temperatures of 4 degrees C, 24 degrees C and 40 degrees C. At the end of 28 days greater than 90% of initial concentrations of INH, PZA and RIF in monosuspensions remained unchanged irrespective of ambient temperature as was the case with INH and PZA in cosuspension. The addition of RIF to either INH or PZA in cosuspension or together in multisuspension led to a marked fall in the concentration of one or more of the agents, an effect that was accentuated by the addition of vitamin C. In the case of a multisuspension of INH + RIF + PZA with vitamin C added, 41.7% (4 degrees C), 24.1% (24 degrees C) and 20.3% (40 degrees C) of initial INH concentrations and 1.9% (4 degrees C), 1.3% (24 degrees C) and 0.0% (40 degrees C) of initial RIF concentrations remained detectable after 28 days. The addition of vitamin C to monosuspensions of INH and PZA led to a marked decline in the amount of drug detectable and only in the case of RIF was greater than 90% of initial concentrations of the drug detectable after 28 days. The dispensing of cosuspensions or multisuspensions of antituberculosis agents containing RIF is inadvisable as is the addition of vitamin C in any form. PMID- 1749697 TI - Pityriasis rosea. PMID- 1749696 TI - Miliary tuberculosis in children: a review of 94 cases. AB - This is a retrospective review of the clinical, radiologic and laboratory features of 94 cases of childhood miliary tuberculosis seen during a 5-year period, 1985 to 1989. A history of Bacillus Calmette-Guerin vaccination was documented in 88% of children. The median age at presentation was 10.5 months, 52% of cases occurring in those younger than 1 year. The presenting symptoms were nonspecific: cough (72%); fever (61%); loss of appetite and weight (40%); and diarrhea and vomiting (33%). The main presenting signs were hepatomegaly (82%), splenomegaly (54%), lymphadenopathy (46%) and pyrexia (39%). Most of the patients were malnourished and anergic. Meningitis occurred in 19% of patients and this was the only significant risk factor identified for mortality, the overall case fatality rate being 14%. The diagnosis in the vast majority was made on the clinical presentation supported by a classic miliary pattern on chest roentgenogram (91% of cases). Mycobacterium tuberculosis was cultured in 33% of cases. In addition a review of hospital admissions from 1981 to 1989 revealed that annually miliary tuberculosis in children and adults accounted for 8.3 and 1.3%, respectively, of all tuberculosis admissions. This study confirms that miliary tuberculosis is a relatively common complication of tuberculosis in young children. PMID- 1749698 TI - Spinal epidural abscess in infancy: successful percutaneous drainage in a nine month-old and review of the literature. PMID- 1749699 TI - The effects of maternal antibodies on neonatal rotavirus infection. PMID- 1749700 TI - Fatal intrauterine meningococcal infection. PMID- 1749701 TI - Peritonitis with Paecilomyces complicating peritoneal dialysis. PMID- 1749702 TI - Ceftriaxone failure in meningitis caused by Streptococcus pneumoniae with reduced susceptibility to beta-lactam antibiotics. PMID- 1749703 TI - Trimethoprim/sulfamethoxazole-resistant nontypable Haemophilus influenzae. PMID- 1749704 TI - Growth retardation, congenital heart disease and thrombocytopenia in a newborn infant. PMID- 1749705 TI - Zidovudine therapy in thrombocytopenic human immunodeficiency virus-infected children. PMID- 1749706 TI - Management of asymptomatic bacteriuria. PMID- 1749707 TI - Controlling cancer chemotherapy-induced emesis. An update. AB - Cytotoxic chemotherapy can induce acute, delayed and anticipatory nausea and vomiting. The efficacy and toxicity data of the available anti-emetics and their role in chemotherapy-induced emesis are reviewed. Moreover, some pitfalls in the methodology of anti-emetic trials as well as factors known to affect the individual sensitivity of patients for the emetic challenge are illustrated. So far, high-dose metoclopramide (3-6 mg.kg-1.d-1) was the most effective single agent in the control of acute emesis. However, extrapyramidal reactions caused by its dopamine antagonism remained a major drawback. The addition of dexamethasone and/or lorazepam decreases the incidence of extrapyramidal reactions, and further improves anti-emetic control. In animals, serotonin type 3 receptor antagonists have demonstrated promising anti-emetic results against chemotherapy-induced and radiotherapy-induced emesis; the results of clinical studies are awaited. Delayed nausea and vomiting have not been studied as extensively. At present, the combination of metoclopramide and dexamethasone offers an optimal protection in approximately 50% of patients on cisplatin chemotherapy. Anticipatory nausea and emesis remain major problems, and an effective pharmacological treatment is lacking. Attempts to control this type of emesis focus on drugs with amnesic properties and on behaviour therapy. PMID- 1749708 TI - Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfamethomidine in humans. AB - Sulfamethomidine metabolism was studied in 6 volunteers. In humans, only N1 glucuronidation and N4-acetylation take place, leading to the final double conjugate N4-acetylsulfamethomidine N1-glucuronide. The N1-glucuronides were directly measured by high pressure liquid chromatography. Fast and slow acetylators show a similar half-life for sulfamethomidine (26 +/- 6 h) and its conjugates sulfamethomidine (26 +/- 6 h) and N4-acetylsulfamethomidine (36 +/- 16 h). Approximately 50-60% of the oral dose of sulfamethomidine is excreted in the urine, leaving 40-50% for excretion into bile and faeces. The main metabolite of sulfamethomidine is its N1-glucuronide, which accounts for 36 +/- 7% of the dose, followed by N4-acetylsulfamethomidine (16 +/- 8%). N1-glucuronidation results in a 75% decrease in protein binding of sulfamethomidine. N4-acetylsulfamethomidine and its N1-glucuronide showed the same high protein binding of 99%. The renal clearance of N4-acetylsulfamethomidine is 7.9 +/- 2.2 ml/min and approximately 20 times as high as that of the parent drug (0.46 +/- 0.16 ml/min). Total body clearance of sulfamethomidine is 4.5 +/- 0.9 ml/min and the volume of distribution in steady state 10.6 +/- 1.7 1. No measurable plasma concentrations of the N1-glucuronides from sulfamethomidine are found in plasma. This may be explained by renal glucuronidation after active tubular reabsorption. PMID- 1749709 TI - Ofloxacin intravenous. Compatibility with other antibacterial agents. AB - The physical and chemical compatibility of ofloxacin (infusion solution 100 ml = 200 mg) with amoxicillin, amoxicillin + clavulanic acid, flucloxacillin, tobramycin, gentamicin, clindamycin, vancomycin, ceftazidime and piperacillin was investigated. Upon admixture with flucloxacillin a precipitate formed between 7 and 24 hours. No other physical or chemical incompatibilities were observed with any of the other combinations. Ofloxacin may be safely combined with the tested antimicrobial drugs, except for flucloxacillin. PMID- 1749710 TI - In vitro and in vivo comparison of creams containing dithranol 0.5%. AB - In an in vitro model, the release and penetration through a silicon membrane of different cream formulations and ointments containing 0.5% dithranol were studied. The results indicated that the method is not suitable for predicting in vivo release and penetration. Experiments with rabbits showed that the degree of skin irritation produced by a hospital-prepared product containing 0.5% dithranol was comparable to that of of a commercial product. Clinical efficacy and side effects of these two products were investigated in a double-blind left-right comparative study in 35 patients with chronic plaque psoriasis. The two creams proved to be equally effective and showed the same incidence of side-effects. PMID- 1749711 TI - Omeprazole. A pharmaco-epidemiological study of its use in a university hospital. AB - A pharmaco-epidemiologic study in hospitalized patients was carried out in order to establish the place and use of omeprazole (Losec), a new and promising drug in the treatment of acid-related diseases. A comparison is made with cimetidine and ranitidine use. It appeared that prescribed omeprazole doses were high in relation to the established defined daily doses and that substitution of H2 receptor antagonists by omeprazole led to tremendously increased drug costs. From the clinical indication data it could be established that the drug was prescribed appropriately. PMID- 1749713 TI - Abstracts of papers. Clinical pharmacological meeting. Utrecht (The Netherlands), 4 October 1991. PMID- 1749712 TI - Abstracts of posters. Drug utilization research and pharmacoepidemiology meeting. Leiden (The Netherlands), 13 December 1991. PMID- 1749714 TI - Abstracts of papers. Biopharmaceutical meeting. Leiden (The Netherlands), 13 October 1991. PMID- 1749715 TI - Morning sickness. PMID- 1749716 TI - Anaemia. PMID- 1749717 TI - Status regarding development of infrastructural facilities in India: the primary health care approach. PMID- 1749718 TI - Noise-induced hearing impairment and health problems of the industrial workers. PMID- 1749719 TI - Self retaining catheter: a brief manual. PMID- 1749720 TI - About nurses and nursing. PMID- 1749722 TI - Maintaining professional ethics and discipline in nursing. PMID- 1749721 TI - Nurses in psychiatric rehabilitation. PMID- 1749723 TI - Module on weaning and supplementary feeding. PMID- 1749724 TI - A study of complications of intravenous therapy in children. PMID- 1749725 TI - You and your child: the need for love and security. PMID- 1749726 TI - Attitude of unmarried girls towards family planning: a study in an Orissa City. PMID- 1749727 TI - European multicenter prospective follow-up study of 1,002 implants of a single lead VDD pacing system. The European Multicenter Study Group. PMID- 1749728 TI - Blood transfusion reactions. Which are life-threatening and which are not? AB - Adverse reactions occur acutely or some time after the fact in 20% of all blood transfusions. Since reactions are so common, it is important to recognize quickly whether the reaction is easily correctable or serious enough to force discontinuation or modification of treatment. The authors present a practical discussion of the topic, classifying reactions in terms of clinical presentation rather than pathophysiologic description. PMID- 1749729 TI - Hypothyroidism in the elderly. When symptoms are not a 'normal' part of aging. AB - Clinical findings alone may not lead to prompt diagnosis of hypothyroidism in elderly patients. Therefore, routine thyroid function tests may be warranted in older patients, especially women. Serum thyrotropin (TSH) is the most sensitive marker for hypothyroidism, although the test is more costly than that for serum thyroxine (T4). Patients with overt hypothyroidism who have elevated TSH and low T4 levels require replacement therapy. In addition, patients who have a TSH level higher than 20 microU/mL or who have a mildly elevated TSH level and high titers of antithyroid antibodies may benefit from prophylactic treatment. The usual recommended replacement dose is 0.05 to 0.1 mg/day of levothyroxine sodium (Levothroid, Synthroid). PMID- 1749730 TI - Understanding serum electrolytes. How to avoid mistakes. AB - Serum electrolyte levels by themselves may be difficult to interpret. For example, an abnormal serum potassium concentration cannot be understood without taking into account the patient's history, other serum electrolyte values, and possibly results of other laboratory tests. Knowledge of the principles of serum electrolyte concentrations, therefore, is an important adjuvant to understanding their implications. PMID- 1749731 TI - Adult respiratory distress syndrome. Strategies to provide support and enhance oxygen delivery. AB - Respiratory failure itself is rarely the cause of death in patients with adult respiratory distress syndrome (ARDS). The multiple-organ failure that often accompanies the syndrome or the underlying disease or trauma that leads to ARDS is more frequently the cause. Thus, care of these patients consists of providing life-sustaining support until they respond to therapy. The authors explain what happens in respiratory failure and how gas exchange can be enhanced in these critically ill patients. PMID- 1749732 TI - Corticosteroid therapy for rheumatoid arthritis. Benefits and limitations. AB - Oral corticosteroids, despite their potential side effects, have a select role in the treatment of rheumatoid arthritis. For articular disease, these drugs must be targeted to short-term goals, such as symptom relief. Close attention to the indications and potential hazards of steroid therapy may ensure optimal benefit and reduced risk. Intra-articular steroid injections can provide local symptomatic relief when only one or a few joints are swollen. Septic arthritis is most important to exclude before injection of a joint. Complications of intra articular injection are few, and relief may be long-lasting. PMID- 1749733 TI - Social phobia. Helping patients who are disabled by fear. AB - Persistent fear of embarrassment or humiliation in social situations can paralyze a person's educational and career advancement and lead to loneliness and isolation. What are the clinical signs of social phobia? How does it lead to disability and impairment? Dr Marshall answers these questions and discusses differential diagnosis and management. PMID- 1749734 TI - Hepatitis C update. New answers, new questions. AB - Currently available tests for infection with the hepatitis C virus detect the presence of antibodies against the virus. The value of these tests is limited, however, because the appearance of antibodies may be delayed and because there is a significant rate of false-positive results. Supplementary tests now being developed should greatly facilitate diagnosis of hepatitis C. Patients with chronic liver disease due to the hepatitis C virus can be treated with interferon alfa-2b (Intron A). This treatment should also be considered for patients with markedly elevated transaminase levels, evidence of significant histologic injury, or symptoms referable to the liver. PMID- 1749735 TI - A bright spot in winter. PMID- 1749736 TI - Leishmaniasis. Another threat to Persian Gulf veterans. AB - Leishmaniasis, a protozoal infection transmitted by sand flies, is one of the most common parasitic diseases worldwide. As US military troops return from endemic areas, it is likely that physicians will encounter cases of this previously seldom seen disease. The incubation period is long, and initial infection is often insidious and difficult to diagnose. To prevent the high mortality of untreated visceral forms and the potentially disfiguring scarring of the cutaneous form, primary care physicians (especially those caring for Persian Gulf veterans) should be aware of the disease and familiar with its treatment. PMID- 1749737 TI - Delayed weakness following a gunshot wound. AB - Injury to the vascular system in the cervical mediastinal area can cause delayed neurologic symptoms. In this article, the authors describe a patient in whom pseudoaneurysm formation after a gunshot wound eventually led to weakness in the shoulder and arm. PMID- 1749738 TI - Triglycerides and serum cholesterol. PMID- 1749739 TI - Ischemic stroke. How to keep the first one from happening. AB - The prevention of stroke has undenied merit. Recognition of stroke-inducing conditions (eg, cardiac diseases associated with embolism, polycythemia) provides opportunities for specific prevention strategies. For a larger number of patients, however, risk factors for degenerative vascular disease should be addressed. The evidence for efficacy is strongest for treatment of hypertension, and smoking cessation also reduces the risk of stroke. The value of treatment of hyperlipidemia in reducing the incidence of a first stroke remains to be demonstrated. Optimal management of carotid bruit and asymptomatic stenosis will be clarified by results of ongoing clinical trials. On the basis of available data, use of aspirin by healthy persons without risk factors cannot be recommended as a method for preventing a first ischemic stroke. PMID- 1749740 TI - Cardioembolic stroke. Primary and secondary prevention. AB - Modern prospective trials have recently shown that warfarin prescribed to produce less anticoagulant effect than was customary in the past reduces cardioembolic stroke by up to 80% in patients with nonvalvular atrial fibrillation. These results represent a major advance in stroke prevention. The effectiveness of antithrombotic treatment in other settings in which there is risk of cardioembolism is less well established but likely to be substantial. PMID- 1749741 TI - Prevention of recurrent ischemic stroke. AB - Treatment after an ischemic stroke or transient ischemic attack (TIA) should target the presumed cause of the initial episode to facilitate focused prophylaxis. In the majority of ischemic strokes, degenerative large- and small vessel disease is the cause. In these patients, attention to modifiable risk factors is an important priority. However, uncertainty and controversy remain regarding therapy, although issues are gradually being settled. There are now strong scientific data to support the use of carotid endarterectomy in patients with 70% to 99% stenosis and an ipsilateral TIA or nondisabling stroke. Aspirin is accepted as standard preventive therapy and should be used in all patients with a TIA or stroke, including those who undergo endarterectomy. Although the dose most commonly used in clinical trials is 1,300 mg/day, a daily dose of 325 mg is probably equally effective with less gastrotoxicity. Given present evidence, use of dipyridamole (Persantine) is not warranted. The role of ticlopidine hydrochloride (Ticlid) in stroke prophylaxis is not well defined. Its superiority over aspirin demonstrated in one study may make it the drug of first choice despite its expense and side effects. The efficacy of warfarin sodium (Coumadin, Panwarfin, Sofarin) or heparin in ischemic stroke caused by degenerative cerebrovascular disease is not supported by scientific data, but no prospective controlled studies have demonstrated that these agents are ineffective. Therefore, it seems prudent to reserve anticoagulant therapy for situations in which an ongoing thrombotic process is likely (eg, progressing stroke). Heparin therapy in the immediate post-TIA period is not warranted on the basis of current scientific evidence. PMID- 1749742 TI - Antiarrhythmic drug therapy in congestive heart failure. Indications and complications. AB - High-grade ventricular arrhythmias are common in congestive heart failure (CHF). However, antiarrhythmic drug therapy is indicated only for patients with symptomatic or hemodynamically significant sustained arrhythmias. Before such therapy is initiated, reversible causes of arrhythmias (eg, electrolyte imbalance, drug interactions and toxicity, decompensation of CHF, ongoing ischemia) should be sought out and corrected. Patients with poor ventricular function or a history of CHF should be hospitalized and monitored continuously during initiation and evaluation of antiarrhythmic therapy so that early detection of proarrhythmic response is possible. Therapy should be initiated with the smallest effective dose, which then is increased slowly to minimize the risk of side effects. Drug selection should be guided electrophysiologically or noninvasively, and empirical antiarrhythmic drug therapy must be avoided. PMID- 1749743 TI - Tumour necrosis factor in inflammation: relation to other mediators and to macrophage antitumour defence. PMID- 1749744 TI - Molecular action of class I antiarrhythmic drugs and clinical implications. AB - This report briefly reviews the advance in our knowledge of cellular electrophysiological effects of membrane stabilizer antiarrhythmic drugs (sodium channel blockers) including some new ones. The class I drugs block cardiac sodium channels and differ in the kinetics of the interaction with sodium channels and in the actions on the repolarization phase. The class I drugs can be subdivided into subclasses (I a,b,c). This review focuses on the interaction of these drug with sodium channels and the molecular models of their action. The interaction of class I drugs with the sodium channel receptor is influenced by the state of the myocardium (pH, ischaemia) and by other drugs as well. The clinical implications of different actions of sodium channel blockers, alone and in combination, and their proarrhythmic effects are summarized. PMID- 1749745 TI - The in vitro effects of lipid peroxidation on the content of individual forms of cytochrome P-450 in liver microsomes of guinea-pigs. AB - The effect of lipid peroxidation in vitro on the amounts of several forms of cytochrome P-450 in liver microsomes from guinea-pigs was investigated. Lipid peroxide formation in liver microsomes from ascorbic acid (VC)-deficient animals was much higher than that observed in control animals. The antibodies to rat P 450IA2 (P-448-H), P-450IIB1 (P-450b) and human P-450IIIA4 (P-450NF) recognized one or two forms of cytochrome P-450 in liver microsomes of guinea-pigs. Neither cytochrome P-450 cross-reactive with anti-P-450IIB1 antibodies nor cytochrome P 450 cross-reactive with antibodies to P-450IIIA4 was virtually affected by microsomal lipid peroxidation induced by NADPH in vitro. In contrast, the forms of cytochrome P-450 immunochemically related to P-450IA2 were decreased with the increased level of lipid peroxide formation. The form-specific degradation of cytochrome P-450 due to lipid peroxidation was in agreement with our previous observation that the amounts of cytochrome P-450 cross-reactive with antibodies to P-450IA2 but not with antibodies to P-450IIIA (P-450PB-1) were predominantly decreased in VC-deficient guinea-pigs compared to control animals in vitro. PMID- 1749746 TI - Different effects of captopril and other angiotensin converting enzyme inhibitors on cardiovascular preparations. AB - The effects of captopril and of other angiotensin-converting enzyme inhibitors (zofenopril, fosenopril and enalaprilic acid) were tested on the isolated rabbit heart and aorta. Captopril elicited an erratic negative inotropic effect and a reduction in basal coronary perfusion pressure (10(-5)-10(-4) M). The increase of coronary perfusion pressure induced by vasopressin, methoxamine, angiotensin II and Bay K 8644 was partially antagonized by captopril (10(-7)-10(-4) M) in a non specific manner. These actions were not modified by saralasin or indomethacin and by ex vivo pretreatment with captopril itself. On the aortic strips, the contraction plateau induced by KCl and angiotensin II was partially inhibited (10(-6)-10(-4) M), while no effect was observed on those induced by noradrenaline, serotonin and PGF2 alpha. The Ca2+ concentration-response curve appeared shifted to the right in a non-competitive manner. The other angiotensin converting enzyme inhibitors showed no effect up to 10(-4) M on isolated heart or aorta. Results obtained with captopril were consistent with vasorelaxant activity independent of the tissue renin-angiotensin system. Modulatory activity on the intracellular calcium movement may be involved. PMID- 1749747 TI - Effects of different drugs on the cystometrogram in conscious rats. AB - The effects on urodynamic parameters of i.v. administration of different drugs utilized in the therapy of detrusor instability, have been studied in conscious catheterized rats. Emepronium bromide, oxybutynin and nifedipine affected in a dose-dependent way the micturition pressure (MP), with sporadic changes in bladder volume capacity (BVC). Terodiline induced significant increases in BVC values in a wide range of doses. These changes, however, were always not dose dependent. The drug significantly reduced MP only at the higher administered dose (10 mg/kg). Flavoxate induced increases of bladder capacity (BVC) not dependent on the administered doses, with no changes in micturition pressure (MP). Indomethacin significantly increased BVC and weakly reduced MP, but the effects were not dose-related. The effects of drugs on BVC were unrelated with the basal value of this parameter, whereas the decrease of MP seems to be related to high basal values before treatment. From a quantitative point of view, cystometrographic recordings in conscious normal rats can provide comparative data among drugs acting on bladder contractility (MP) such as anticholinergics and strong calcium antagonists. PMID- 1749748 TI - Clonidine differentially modulates the release of endogenous GABA in various rat brain areas. AB - The effects of clonidine on the release of endogenous gamma-aminobutyric acid (GABA) have been studied in superfused synaptosomes prepared from rat hypothalamus, nucleus tractus solitarii (NTS) and cerebellum. Clonidine enhanced in a concentration-dependent manner the basal release of GABA from hypothalamus and NTS synaptosomes. In contrast, the imidazoline did not affect the release of the amino acid from the cerebellar preparation. The alpha 2-adrenoceptor antagonist yohimbine prevented the releasing effect of clonidine, while the alpha 1-adrenoceptor antagonist prazosin was ineffective. The results show that the release of GABA from hypothalamus or NTS nerve endings can be enhanced by clonidine through the activation of adrenoceptors of the alpha 2 subtype. The GABAergic nerve terminals of cerebellum do not seem to possess presynaptic adrenoceptors by which clonidine can regulate the basal outflow of the amino acid. The results suggest that some of the clonidine effects may occur through activation of the GABA system. PMID- 1749749 TI - The role of the adrenergic system in the heart: regulation of contractility by cardiac adrenoceptors. PMID- 1749750 TI - Spectral analysis of cardiovascular variabilities in the assessment of sympathetic cardiac regulation in heart failure. PMID- 1749751 TI - [Tuberculin diagnosis and its significance in massive BCG re-vaccination]. AB - The diagnosis of primary tuberculosis contamination becomes difficult and the effectiveness of tuberculin diagnosis drastically declines under conditions of mass vaccination and threefold revaccination of children. Study of the influence of different intervals between BCG revaccination on the nature of tuberculin sensitivity was carried out in order to improve the preventive measures in children and adolescents. An increase in revaccination intervals was found to contribute to a more precise detection of primary tuberculosis contamination and larger (more than four times) BCG coverage of adolescents. PMID- 1749752 TI - [BCG vaccination of children with differing perinatal pathology]. AB - Information on 586 newborns with perinatal abnormalities who were not given BCG vaccination in the maternity homes of Novosibirsk is analysed. The most common causes of BCG vaccination refusal were intrauterine hypotrophy (35%), CNS affection (29.2%) and prematurity (22.7%). A follow-up of 693 children with perinatal abnormalities who received BCG vaccination in polyclinics has shown that this vaccination is sufficiently effective and the course of the vaccination reaction does not differ from that in children who were vaccinated in the maternity homes. It has been concluded that BCG vaccination can be given to the majority of children with perinatal abnormalities within the first 2 months of life provided their condition is satisfactory. PMID- 1749753 TI - [The differential diagnosis of sarcoidosis of the respiratory organs using mathematical methods and computers]. AB - A system for detecting sarcoidosis has been proposed on the basis of the results of a primary examination, which comprises a combination of programs for determining whether sarcoidosis may occur in various X-ray syndromes (enlarged intrathoracic lymph nodes, disseminated process, infiltrative or pneumonia-like shadow and cavity formation). The system has been developed with the help of a program-algorithm complex which enables one to make the dialogue system of the decision-make support on the basis of statistical methods of "image recognition" containing basic structural elements of the expert systems. Program development proceeds from the findings obtained in 406 patients with sarcoidosis of respiratory organs and 723 patients having similar clinical and X-ray picture of the disease. The diagnostic efficiency of the system was 89% in disseminated processes, 90% in enlarged intrathoracic lymph nodes and cavitary changes, and 96.2% in infiltrative changes. PMID- 1749754 TI - [The incretory function of the pancreas in patients with pulmonary tuberculosis and diabetes mellitus]. AB - Serum C-peptide levels were studied in 88 patients with pulmonary tuberculosis concurrent with diabetes mellitus. The pancreatic incretory function in combined pathology was found to be related both to the type and severity of diabetes mellitus and the severity of tuberculosis. Specific and medicamental intoxication negatively affects residual insulin secretion and the body's insulin-sensitivity. High functional capacity of B-cells of the pancreas and insulin resistance in noninsulin dependent diabetes, on the one hand, and rapid depletion of the insular apparatus in serious chronic tuberculosis, on the other, made it possible to recommend combined hypoglycemic therapy with insulin and oral sugar-lowering drugs to patients with a prolonged severe course of each of the diseases (pulmonary tuberculosis and Type II diabetes) in their combination. PMID- 1749755 TI - [Tarivid in the combination therapy of patients with pulmonary tuberculosis]. AB - The effectiveness of tarivid, a new drug having a broad spectrum of antimicrobial action and antituberculous effect, was studied. The drug was given to 29 patients with newly detected destructive pulmonary tuberculosis and bacillary excretion. Eight patients had microbacterial resistance to streptomycin, rifampicin and isoniazid, 12 had tolerance to them, in 9 patients tuberculosis was complicated by a nonspecific inflammatory process. The course of treatment ranged from 3 weeks to 3 months. The drug was well tolerated. Its effect was manifested by reduction of intoxication, resolution of the inflammatory and pericavitary pulmonary lesions and bacilli absence. Tarivid can be considered an efficacious drug in the multimodality therapy of tuberculosis patients. PMID- 1749756 TI - [The use of bio-controlled electrostimulation of the respiration in the combined modality treatment of patients with pulmonary tuberculosis]. AB - Electric respiration stimulation (ERS) synchronized with the onset of spontaneous breathing is more effective than induced one. Introduction of the biocontrolled ERS into the treatment and prevention of respiratory complications in the postoperative period improved the effectiveness of surgical treatment of phthisiopulmonologic patients. The biocontrolled ESR is known to provide favourable results in the multimodality treatment of patients with pneumonia, chronic bronchitis and bronchial asthma. PMID- 1749757 TI - [Diagnosis of ocular tuberculosis]. AB - Ways for enhancing the diagnostic accuracy for tuberculous diseases of the eyes and shortening the terms of examination of patients are shown on the basis of research and the elaboration of new early diagnostic methods. It is only further work in this direction that will promote the improvement and accuracy of the diagnosis of tuberculous uveitis. PMID- 1749758 TI - [The surgical treatment of disseminated forms of tubercular spondylitis using Byzov's apparatus]. AB - Analysis of treatment of 123 patients with disseminated forms of tuberculous spondylitis is presented. Among the patients 67 (54.4%) subjects were over 55 years of age. The main cause of disseminated spondylitis forms was ungroundlessly prolonged conservative treatment under bed regime. As a result, symptoms of low cardiac activity were seen in 79 (64.2%), lymphovenous stasis in 22 (17.8%) and osteoporotic signs in 38 (30.8%) patients. Complications and concurrent diseases in 41 (33.3%) of the cases prompted surgery from the posterior approach, in 82 (66.7%)--from the anterior approach with replacement of the defect by an autograft or biocompatible implant with extrafocal posterior fixation of the operated segments by Byzov's apparatus. The patients became active beginning on days 7-12 of postoperation, which promoted reparative process normalization in the operative area. The late therapeutic results were studied in 117 patients. Support capacity recovered in 99 patients and improved in 18. The method used is functionally justified, well tolerated by patients and highly effective in treating the abnormality. PMID- 1749759 TI - [Characteristics of primary tuberculosis from the morphologic point of view (lecture)]. PMID- 1749760 TI - [The method of endobronchial thermometry in the evaluation of the activity of tuberculosis of the respiratory organs]. AB - Local temperature reactions were studied in 72 patients with intrathoracic tuberculosis (64 of them had active tuberculosis and 8 residual pulmonary changes after prior tuberculosis). Endobronchial thermometry in the dynamics of a specific process was conducted in 7 patients with pulmonary tuberculosis. Bronchial temperature was measured during fibrobronchoscopy under local anesthesia by a device of an original design. Marked thermoregulatory disturbances were found in the bronchi which were caused by a specific active process in the lungs and were manifested in a significant decline of endobronchial temperature as compared to normal values. Clinical recovery of pulmonary tuberculosis with the development of posttuberculous fibrous changes does not cause any disturbances in local temperature reactions. The temperature level in the bronchi is significantly affected by the nature and degree of the inflammatory process in the bronchi. PMID- 1749761 TI - [AIDS and lung diseases]. PMID- 1749762 TI - [The NBT test of alveolar macrophages in patients with infiltrative pulmonary tuberculosis]. PMID- 1749763 TI - [Hemofiltration in the treatment of patients with renal tuberculosis and tuberculosis of other organs, complicated by chronic renal insufficiency]. PMID- 1749764 TI - [The voluntary limitation of lung ventilation and suppression of expiration in the treatment of bronchial asthma]. PMID- 1749765 TI - [The use of highly dispersed iron particles for increasing the sensitivity of the luminescent microscopic method of determining Mycobacterium tuberculosis]. AB - A highly dispersed ferromagnetic powder obtained by a plasmochemical method (particle size was 100-500 A) was treated by means of an ultrasonic disperser: suspension was added to the trisodium phosphate homogenized and neutralized sputum (0.3 mg of the initial powder per 1 ml of sputum) of patients with various forms of pulmonary tuberculosis. The sputum was then incubated at slight stirring for 40 min and centrifuged; the precipitate was used to prepare smears which were stained with auramine; mycobacteria were detected by luminescence microscopy. The ferromagnetic suspension was found to increase luminescence microscopy sensitivity to 85.4%. The efficacy of the method was 30.8% more than that in the cultivation of infectious material in solid nutrient media. PMID- 1749766 TI - [Dynamics of the indices of the immune system as affected by endobronchial laser therapy in patients with complicated tuberculosis of the lungs]. AB - The results of study of the local and humoral immune defense during endobronchial laser therapy of nonspecific endobronchitis in patients with newly diagnosed pulmonary tuberculosis are presented. Laser therapy proved to have no negative action on the humoral immunity in pulmonary tuberculosis patients during treatment of catarrhal and purulent endobronchitis, while a marked increase in IgM levels, thus rapidly reacting and well opsonizing antibodies can be regarded as a positive or stimulating the impact on the whole immune system. Endobronchial laser therapy for catarrhal and especially purulent inflammatory bronchial process in the multimodality treatment of patients with newly diagnosed pulmonary tuberculosis normalized parameters of the local immune system, especially that of locally secreted immunoglobulins, i.e. helium-neon laser radiation has a favourable influence on local immune defense, which is essential in increasing the efficacy of therapy of this category of patients. PMID- 1749767 TI - [Potentialities and perspectives for the use of thermographic methods in phthisiology and pulmonology]. PMID- 1749768 TI - [The 70th anniversary of the Chair of Phthisiopulmonology of the I.M. Sechenov Moscow Medical Academy]. PMID- 1749769 TI - [Apropos of V.M. Kolomiits's article "Administrator-phthisiologist in current conditions"]. AB - The editorial board of the journal presented for discussion the paper by V. M. Kolomiyits "A phthisiological curator under the present-day conditions". Four review papers have been received which are concerned with pro and contra of the activity of a phthisiological curator. All the participants of the discussion supported the idea of remaining curator's activities in either form. PMID- 1749770 TI - An autoantibody to single-stranded DNA: comparison of the three-dimensional structures of the unliganded Fab and a deoxynucleotide-Fab complex. AB - Crystal structures of the Fabs from an autoantibody (BV04-01) with specificity for single-stranded DNA have been determined in the presence and absence of a trinucleotide of deoxythymidylic acid, d(pT)3. Formation of the ligand-protein complex was accompanied by small adjustments in the orientations of the variable (VL and VH) domains. In addition, there were local conformational changes in the first hypervariable loop of the light chain and the third hypervariable loop of the heavy chain, which together with the domain shifts led to an improvement in the complementarity of nucleotide and Fab. The sugar-phosphate chain adopted an extended and "open" conformation, with the base, sugar, and phosphate components available for interactions with the protein. Nucleotide 1 (5'-end) was associated exclusively with the heavy chain, nucleotide 2 was shared by both heavy and light chains, and nucleotide 3 was bound by the light chain. The orientation of phosphate 1 was stabilized by hydrogen bonds with serine H52a and asparagine H53. Phosphate 2 formed an ion pair with arginine H52, but no other charge-charge interactions were observed. Insertion of the side chain of histidine L27d between nucleotides 2 and 3 resulted in a bend in the sugar-phosphate chain. The most dominant contacts with the protein involved the central thymine base, which was immobilized by cooperative stacking and hydrogen bonding interactions. This base was intercalated between a tryptophan ring (no. H100a) from the heavy chain and a tyrosine ring (no. L32) from the light chain. The resulting orientation of thymine was favorable for the simultaneous formation of two hydrogen bonds with the backbone carbonyl oxygen and the side chain hydroxyl group of serine L91 (the thymine atoms were the hydrogen on nitrogen 3 and keto oxygen 4). PMID- 1749771 TI - Thiol proteases and aldehyde dehydrogenases: evolution from a common thiolesterase precursor? AB - The C-terminal 222 residues of human liver aldehyde dehydrogenase can be aligned with the C-terminal 226 residues of a thiol protease from Dictyostelium discoideum to yield 47 residue identities, including matching active site cysteine residues. A multiple alignment with three more aldehyde dehydrogenases and three more thiol proteases yields three regions with clustered residue similarities. In the tertiary structure of papain, these three regions are in close proximity although widely separated in primary structure, and many conserved residues are located in the active site groove. The three-dimensional relationships, the common thiol ester mechanisms of the enzymes, the locations of exon boundaries in the dehydrogenase and protease genes, and the conservation of internal salt-bridging and disulfide-paired residues in papain, all appear compatible with the hypothesis of an ancestral relationship between thiol proteases and aldehyde dehydrogenases. PMID- 1749772 TI - A 175-psec molecular dynamics simulation of camphor-bound cytochrome P-450cam. AB - The structure and internal motions of cytochrome P-450cam, a monooxygenase heme enzyme with 414 amino acid residues, with camphor bound at the active site have been evaluated on the basis of a 175-psec molecular dynamics simulation carried out at 300 K. All hydrogen atoms were explicitly modeled, and 204 crystallographic waters were included in the simulation. Based on an analysis of the time course of the trajectory versus potential energy, root mean square deviation, radius of gyration, and hydrogen bonding, the simulation was judged to be stable and representative of the average experimental structure. The averaged structural properties of the enzyme were evaluated from the final 135 psec of the simulation. The average atomic displacement from the X-ray structure was 1.39 A for all heavy atoms and 1.17 A for just C-alpha atoms. The average root-mean square (rms) fluctuations of all heavy atoms and backbone atoms were 0.42 and 0.37 A, respectively. The computed rms fluctuations were in reasonable agreement with the experimentally determined temperature factors. All 13 segments of alpha helix and 5 segments of beta-sheet were well preserved with the exception of the N-terminal half of helix F which alternated between an alpha-helix and a 310 helix. In addition there were in general only small variations in the relative orientation of adjacent alpha-helices. The rms fluctuations of the backbone dihedral angles in the secondary structure elements were almost uniformly smaller, with the fluctuation in alpha-helices and beta-sheets, 31 and 10% less, respectively, than those in nonsecondary structure regions. The reported crystal structure contains kinks in both helices C and I. In the simulation, both of these regions showed high mobility and large deviations from their starting positions. Since the kink in the I helix is at the oxygen binding site, these motions may have mechanistic implications. PMID- 1749773 TI - Collective motions in proteins: a covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations. AB - A method is described for identifying collective motions in proteins from molecular dynamics trajectories or normal mode simulations. The method makes use of the covariances of atomic positional fluctuations. It is illustrated by an analysis of the bovine pancreatic trypsin inhibitor. Comparison of the covariance and cross-correlation matrices shows that the relative motions have many similar features in the different simulations. Many regions of the protein, especially regions of secondary structure, move in a correlated manner. Anharmonic effects, which are included in the molecular dynamics simulations but not in the normal analysis, are of some importance in determining the larger scale collective motions, but not the more local fluctuations. Comparisons of molecular dynamics simulations in the present and absence of solvent indicate that the environment is of significance for the long-range motions. PMID- 1749774 TI - Crystal parameters and molecular replacement of an anticholera toxin peptide complex. AB - TE33 is an Fab fragment of a monoclonal antibody raised against a 15-residue long peptide (CTP3), corresponding in sequence to residues 50-64 of the cholera toxin B subunit. Crystals of the complex between TE33 and CTP3 have been grown from 20% (w/v) polyethylene glycol-8000 at pH 4.0. The crystals are orthorhombic, space group P2(1)2(1)2, with unit cell dimensions a = 104.15, b = 110.61, and c = 40.68 A. X-Ray data have been collected to a resolution of 2.3 A. The asymmetric unit contains one molecule of Fab and one molecule of CTP3. The presence of CTP3 has been demonstrated by fluorescence quenching of the dissolved crystal after X-ray data collection. A molecular replacement solution was found based on the coordinates of DB3, an antiprogesterone Fab fragment. PMID- 1749775 TI - Analysis of the steric strain in the polypeptide backbone of protein molecules. AB - The extent to which local strain is present in the polypeptide backbone of folded protein molecules has been examined. The occurrence of steric strain associated with nonproline cis peptide bonds and energetically unfavorable main chain dihedral angles can be identified reliably from the well ordered parts of high resolution, refined crystal structures. The analysis reveals that there are relatively few sterically strained features. Those that do occur are located overwhelmingly in regions concerned with function. We attribute this to the greater precision necessary for ligand binding and catalysis, compared with the requirements of satisfactory folding. PMID- 1749776 TI - Crystallization and preliminary X-ray diffraction studies of human salivary alpha amylase. AB - Nonglycosylated alpha-amylase, a major component of human parotid saliva, has been crystallized by the vapor diffusion technique using 2-methyl-2,4-pentanediol as the precipitant in the presence of CaCl2 at pH 9.0. The crystals are orthorhombic, space group P2(1)2(1)2(1) with unit cell dimensions of a = 53.3, b = 75.8, and c = 138.1 A. The asymmetric unit contains one amylase molecule. The solvent content is 54%. The crystals are stable to X-rays and diffract up to 2.8 A and appear to be suitable for X-ray diffraction studies. PMID- 1749777 TI - Crystallization and preliminary X-ray investigation of a recombinant form of rat catechol O-methyltransferase. AB - Rat catechol O-methyltransferase cDNA was introduced into an E. coli expression vector pKEX14, which utilizes the inducible T7 promoter. Active and soluble recombinant catechol O-methyltransferase was produced in bacteria and purified to electrophoretic homogeneity by chromatographic procedures. The purified enzyme has been crystallized by the method of vapor diffusion using polyethylene glycol as precipitant. The space group is P3(1)21 or P3(2)21 with a = b = 51.3 A and c = 168.5 A and one molecule in the asymmetric unit. The crystals diffract beyond 3.2 A and are suitable for three-dimensional X-ray structure determination. PMID- 1749778 TI - Asymmetry of mandibular dimensions in European skulls. AB - Eighteen mandibular dimensions (mm) in sex-determined, 10th-12th-century European skulls from burial sites in South-Eastern Hungary were examined to discover whether differences exist between the right and left sides. There was a statistically significant difference in only one dimension, the smallest sagittal diameter of the mandibular neck, in both males and females. The frequencies with which the various 18 dimensions were identical between right and left sides ranged from 39.9% to 82.0% in males, and from 45.9% to 83.2% in females. The examined individual dimensions appeared to be smaller on the right side in 7.0% to 33.7% (mean 19.1%) of the male cases, and in 7.1% to 29.9% (mean 17.9%) of the females, while the right side was larger in 7.7% to 50.9% (mean 22.3%) of the males and in 7.9% to 54.3% (mean 22.5%) of the females. In conclusion, asymmetry of the left and right sides was found between the measured individual mandibular dimensions on average in 41.4% of the males and 40.4% of the females. PMID- 1749779 TI - A new method for studying the effect of glass ionomer on plaque in vivo. AB - In order to study the amount of fluoride originating from glass ionomer, a test appliance was constructed and set on upper molars of sixteen volunteers using glass ionomer. The control appliance was set on the contralateral tooth using composite. Six weeks after the setting of appliances, plaque samples were taken and analysed. Mean amounts of protein corresponding to the amounts of plaque were equal in the test and the control groups. The mean fluoride/protein ratio in plaque was 80 times higher in the glass ionomer group than in the composite group. With this sampling method it is possible to collect sufficient amounts of plaque for quantification of plaque fluoride. PMID- 1749780 TI - Plaque accumulation on glass ionomer filling materials. AB - It has been suggested that fluoride released by glass ionomers inhibits the growth of plaque. The aim of this study was to compare plaque accumulation on glass ionomers and composite. The materials tested were (1) freshly mixed glass ionomer (Ketac-Fil), (2) artificially aged glass ionomer (Ketac-Fil), (3) freshly mixed silver glass ionomer (Ketac-Silver) and (4) light-cured hybrid composite (Valux). Ten volunteers wore an acrylic appliance for three periods of 18 hours, one for each glass ionomer. A glass ionomer disk was inserted on one randomly chosen side of the appliance and the composite disk on the other. The volunteers rinsed once an hour with a 15% sucrose solution. The amount of pellicle and plaque on the disk was estimated by analysing its protein content. During each cycle, more plaque accumulated on the glass ionomers than on the composite (fresh Ketac-Fil/Valux p less than 0.05, aged Ketac-Fil/Valux p less than 0.01, Ketac Silver/Valux NS). On examination using a scanning electron microscope the surfaces of the glass ionomers were found to be markedly more porous, and to contain more microbes, than the composite surface. The presence of silver in the silver glass ionomers may have affected the initial adherence of bacteria. PMID- 1749781 TI - Safety of dental restorative materials: a survey of dentists' attitudes. AB - In order to obtain information from practising dentists in Finland about their experiences of and attitudes to dental restorative materials, a cross-sectional survey was conducted in spring 1990 using a postal questionnaire. The response rate was 73% (454 replies). Virtually all (99%) respondents had faced questions about the safety of dental materials in 1989 and 93% of all questions concerned amalgam. Most respondents assessed their theoretical knowledge and practical experience of amalgam, composite and glass ionomer as good, whereas gold and ceramics as filling materials were less familiar. However, the three latter materials were regarded as safe by most respondents. Composite was believed to pose the highest risk of side-effects. Although few dentists regarded amalgam as hazardous, it was estimated that the use of this material will decrease over the next five years in favour of glass ionomer, ceramic materials and composite. Changing dental fillings at the patient's request without odontological indications was opposed by about 80% of the dentists, even if patients were to bear the total cost themselves. Only 7% of the dentists claimed to be worried about the possible risks to themselves of handling amalgam at work, and 97% reported having amalgam fillings personally. PMID- 1749782 TI - Dental erosion and associated factors among factory workers exposed to inorganic acid fumes. AB - The occurrence of dental erosion and the relative importance of some related factors were explored in a cross-sectional study, using blind dental examinations. A sample of 186 workers from four factories was drawn. Among the 157 dentate participants 76 were working in departments containing acid fumes and 81 controls had never worked under such conditions. Out of the dentate participants, 20 (12.7% had erosion). Anterior teeth were affected more often than posterior ones. Exposure to acid fumes, increasing age and frequency of intake of fruits increased the probability of dental erosion. It can be concluded that exposure to acid fumes in the work environment is associated with dental erosion especially on anterior teeth. PMID- 1749783 TI - The Finnish family competence study: dental oral self-care behaviour and awareness of gingivitis/calculus in fathers of young families. AB - The purpose of this study was to examine oral self-care behaviour and the prevalence of gingivitis and dental calculus in fathers of young families using a questionnaire. The participation rate at 18 months after the birth of the first child was 73.1%. The mean age of the respondents (n = 917) was 28.1 years (range 17-49; SD 4.6). Dental health and dental care were assessed by asking about the existence of gingivitis and dental calculus. Oral hygiene habits were analysed by asking about the use of toothpicks and dental floss and the regularity of toothbrushing. Gingivitis and dental calculus were found to be related to age and to educational and occupational status. The older respondents used dental floss and toothpicks more often and brushed their teeth more regularly than those in the younger age group. When the wife's knowledge was poor, the respondent's oral hygiene habits were also poor. If the wife's knowledge level was good, the young father's oral hygiene was good, too. Parents transfer their own oral health care habits to their children. Respondents whose parents had a high socio-economic status exhibited good oral hygiene habits. The Maternity Health Care Clinic and Well-Baby Clinic network can also influence oral health care habits. The relevant parts of general prophylactic guidance given at these clinics should be included in dental health programmes. PMID- 1749784 TI - The frequency of mother-infant salivary close contacts and maternal caries activity affect caries occurrence in 4-year-old children. AB - Dental caries was investigated in 248 4-year-old children in the Lohja District Health Centre, Finland in relation to the postpartum caries incidence rate in their mothers and the frequency of salivary close contacts between mothers and babies when the latter were 7 months old. Dental caries occurred in 32% of the children. Frequent maternal consumption of sugar-containing foods and drinks was significantly associated with a high maternal caries incidence rate. The mothers who had frequent close contacts with their babies gave them significantly more sweet comforters than the mothers who did not have close contacts frequently. However, only 25% of the children (n = 44) who had frequent maternal close contacts and whose mothers had a high caries incidence rate had caries, although levels of risk factors (bottle feeding with juices, frequent consumption of refined foodstuffs, added sugar and sweets, infrequent toothbrushing) were highest for these children. Dental caries was significantly more frequent in children in whom maternal caries incidence was low and close contacts were frequent (n = 35, 40%) and in those in whom maternal caries incidence was high and close contacts were rare (n = 55, 45%) than in those in whom maternal caries incidence was low and close contacts rare (n = 68, 18%). The results of the study support the theory that maternal caries incidence and salivary contacts with a child are connected with caries infection and immunity. Variations in bacterial challenge via such factors before and during the eruption of teeth may modify caries development in the primary dentition. PMID- 1749785 TI - Nutritional and hormonal regulation of genes for lipogenic enzymes. PMID- 1749786 TI - Trace element-gene interactions with particular reference to zinc. PMID- 1749787 TI - Genetics of obesity and human energy metabolism. PMID- 1749788 TI - Digestion of non-starch polysaccharides by non-ruminant omnivores. PMID- 1749790 TI - Organ-specific measurements of protein turnover in man. AB - Methods that were originally developed for animal studies have now been modified for measuring tissue protein turnover in man with stable isotopes. Of the three techniques which have been discussed, only the arterio-venous difference method has the capacity to measure both the synthesis and degradation. This technique is, however, difficult to perform and has a number of potential sources of error, one of the most important being the assessment of precursor labelling. Constant infusion of a labelled amino acid with measurement of the incorporation into protein of a biopsy is a simpler and more precise technique for measuring synthesis in patients as well as volunteers, but the most appropriate means of assessing the precursor labelling still remains to be worked out. The flooding dose procedure aims to minimize the difficulty of assessing precursor labelling and there is no evidence that the unphysiological dose of labelled amino acid given influences the synthesis rate which is measured. It is rapid to perform and is very well suited to measurements in patients, in whom a wide range of tissues can be studied. These advances in techniques have been facilitated particularly by improvements in mass spectrometry, which have allowed the use of stable in place of radioactive isotopes, and have enabled measurements of isotopic enrichments to be made in small samples of tissue. These techniques for assessing the dynamics of protein metabolism in individual tissues are now being used to answer nutritionally and clinically important questions in human volunteers and patients. PMID- 1749789 TI - Whole-body protein and amino acid turnover in man: what can we measure with confidence? PMID- 1749791 TI - Measurement of energy expenditure: the doubly-labelled-water method in clinical practice. PMID- 1749792 TI - Indirect calorimetry in critical care. PMID- 1749793 TI - Vitamin E and the immune response. PMID- 1749794 TI - Vitamin A and immune function. PMID- 1749795 TI - Selenium and the immune response. PMID- 1749796 TI - Atopy, allergy and the alimentary canal. PMID- 1749797 TI - Fructose intolerance: diet and inheritance. PMID- 1749798 TI - Current perspectives on placental development and its integration with fetal growth. PMID- 1749799 TI - Energy and substrate requirements of the placenta and fetus. PMID- 1749800 TI - Placental transport studied by means of isolated plasma membrane vesicles. PMID- 1749801 TI - Perfusion of isolated human placenta. PMID- 1749802 TI - Human placental trophoblast culture: one-sided and two-sided models. PMID- 1749804 TI - Placental corticotrophin-releasing hormone: activator of the pituitary-adrenal axis in human pregnancy? PMID- 1749803 TI - In vivo measurements of placental transport and metabolism. PMID- 1749805 TI - Determinants of energy density with conventional foods and artificial feeds. PMID- 1749806 TI - Dietary energy density on using sugar alcohols as replacements for sugars. PMID- 1749807 TI - Changes in dietary energy with novel proteins and fats. PMID- 1749808 TI - 'Slimming.'. PMID- 1749809 TI - Obesity and health: why slim? PMID- 1749810 TI - A diet for slimming? PMID- 1749811 TI - Physiological responses to slimming. PMID- 1749812 TI - Exercise for slimming. PMID- 1749814 TI - The media and slimming. PMID- 1749813 TI - The association of slimming with eating disorders. PMID- 1749815 TI - The safety of dieting. PMID- 1749816 TI - The Sir David Cuthbertson Medal Lecture 1990. The effects of injury and joint disease on muscle mass and protein turnover. PMID- 1749817 TI - A chlamydial plasmid is differentially transcribed during the life cycle of Chlamydia trachomatis. AB - A 7.5-kb cryptic plasmid is found in all serotypes of the obligate intracellular parasite, Chlamydia trachomatis. Although at least nine open reading frames are apparent from sequence analysis of plasmid DNA, only a small region of approximately 500 bp has been consistently shown to be transcriptionally active by Northern blot analysis. In this study, transcription was analyzed using a host free system in which RNA synthesized by chlamydiae isolated from host cells was hybridized to different regions of the plasmid. The results suggest that fragments corresponding to all open reading frames are transcribed, but at varied relative levels depending upon the stage of the life cycle. The hybridization patterns also suggested a net chemical degradation of plasmid-specified RNA in a 3' to 5' direction. PMID- 1749818 TI - Nucleotide sequence analysis of the unusually long terminal inverted repeats of a giant linear plasmid, SCP1. AB - SCP1 is a giant linear plasmid of 350 kb coding for the methylenomycin biosynthetic genes in Streptomyces coelicolor. The unusually long terminal inverted repeats present on both ends of SCP1 were analyzed on the nucleotide sequence level. Analysis of six clones containing the terminal 0.35-kb XbaI fragment revealed a slight heterogeneity in the nucleotide sequences of the SCP1 ends. Moreover, it was indicated that this fragment contained seven palindromic inverted repeats and a GT-rich region in the 5'-end strand. The size of the terminal inverted repeats was determined to be 81 kb by the cloning and sequencing of their end-points. An insertion sequence, IS466 was shown to be present just at the end of the right terminal inverted repeat. PMID- 1749819 TI - Low cost device for electrotransformation and its application to the highly efficient transformation of Escherichia coli and Enterococcus faecalis. AB - A simple, low cost device for electrotransformation has been designed and constructed. The cost of the circuit was only $150. Maximum field strength of 12,000 V/cm with an actual time constant up to 11 msec was obtained with a newly designed circuitry and a 0.1-cm electrode gap cuvette. Eschericia coli strains DH1, DH5 alpha, and LE392 were transformed at an efficiency of 10(9)/micrograms DNA with plasmids pUC18 and pBR322. E. faecalis strain OG1X was transformed at an efficiency of 0.9 x 10(5)/micrograms DNA without treatment with glycine. PMID- 1749820 TI - Bacteriophages for incompatibility group H plasmids: morphological and growth characteristics. AB - Two independently isolated temperature-sensitive bacteriophage that are specific for enterobacterial hosts harboring HI and HII plasmids were characterized to determine if any identifiable differences existed between them. The traits examined included adsorption pattern of phage to H pili, bacteriophage size, sensitivity to chloroform, RNA strandedness, reaction with F-specific antiphage serum, virion protein pattern, temperature range of lytic ability, and plaque morphology. No differences between the phages were observed for any of the features analyzed. Ecological questions on the origin and maintenance of temperature-sensitive phages are discussed. PMID- 1749821 TI - A fully modular vector system for the optimization of gene expression in Escherichia coli. AB - The new expression vector system CYTEXP is designed to facilitate the optimization of both transcription and translation in Escherichia coli, while at the same time allowing the exchange of its major components using unique restriction sites. In vitro mutagenesis can be performed in situ using single stranded DNA generated from the bacteriophage f1 ORI sequence. The basic vector pCYTEXP1 bears a synthetic copy of the intercistronic sequence that enhances the translation of the E. coli atpE gene. Reading frames can be inserted directly downstream of this sequence. The bacteriophage lambda promoters, the atpE sequence, the bacteriophage fd transcriptional terminator, the f1 ORI, and the amp antibiotic resistance gene are all borne on exchangeable "modules." Thus, both the efficiency and the conditions of expression of cloned genes can be readily optimized. PMID- 1749822 TI - Identification and mapping of loci involved in motility, adsorption to wheat roots, colony morphology, and growth in minimal medium on the Azospirillum brasilense Sp7 90-MDa plasmid. AB - We have constructed a cosmid library of the Azospirillum brasilense Sp7 90-MDa plasmid (p90) and established the EcoRI restriction map of this plasmid. The central regions of cloned p90 DNA fragments from several recombinant cosmids were deleted by restriction endonuclease digestion and replaced by a DNA cassette encoding kanamycin resistance. Using these in vitro constructed deletions for marker exchange in Sp7, we made six different p90 deletion derivatives spanning all together 50% of the total length of p90. Comparison of the deletion derivatives with Sp7 for several properties revealed p90 loci involved in colony morphology, growth on minimal medium, motility, and adsorption to wheat roots. In analogy with the rhizobial symbiotic plasmids (pSym), we propose to denote the p90 plasmid as a rhizocoenotic plasmid (pRhico), carrying several genes involved in the A. brasilense-plant root interaction. PMID- 1749823 TI - Protein dynamics: comparison of simulations with inelastic neutron scattering experiments. PMID- 1749824 TI - Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective. PMID- 1749825 TI - Development of an "early" detection battery for dementia of the Alzheimer type. AB - 1. To develop a diagnostic battery sensitive to and specific for the early detection of Alzheimer disease (AD) dementia, the authors reviewed over 400 journal articles dealing with the diagnosis of A.D. or senile dementia and cognitive assessment in organic brain dysfunction and closed head injury. 2. We culled those studies that met our criteria for solid, reliable and statistically significant results and recommend the testing paradigms that most often produced good discrimination of mild AD dementia from normal senescence. 3. These include tests of language, verbal and non-verbal memory, perception, praxis, attention and reasoning. 4. The battery we assembled takes less than 1 hour to administer, requires no special equipment, and was designed as an early screen for use by psychologists, psychiatrists and other trained health care professionals; it is not intended for repeated administration, as in pharmacological or longitudinal studies. PMID- 1749826 TI - Cytokines in Alzheimer's disease. AB - 1. Human astrocytoma cells produced biologically active interleukin-6 when treated with a variety of agents including bacterial lipopolysaccharides, viruses, and interleukin-1. 2. Both human recombinant IL-6 and IL-6 produced by stimulated astrocytes promoted differentiation of cultured neuronal cells and reduced survival time in culture. 3. Interleukin-6 and interleukin-1 stimulated the synthesis of the Alzheimer's disease beta-amyloid precursor protein. 4. Cytokines may be involved in stimulation of dystrophic neuritic sprouting, neuronal death, and amyloid deposition noted in the brains of Alzheimer's disease patients. PMID- 1749827 TI - Clonidine and scopolamine: differences and similarities in how they change human information processing. AB - 1. Humans have been tested on a choice reaction time task designed to disclose interactions between stimulus complexity and drug effect. 2. Tests were carried out using oral scopolamine (1.2 mg) and clonidine (0.2 mg). 3. Reaction times and event related potentials were measured. 4. Both drugs slowed reaction time and the N1 component of the ERP. 5. SCOP slows RTs to easy-to-discriminate stimuli more than RTs to harder stimuli. Its effect on P3 is the same for both types of stimuli. 6. CLON tends to slow P3 latencies to easy stimuli more than P3 latencies to harder stimuli, while the RT slowing is almost identical for both types of stimuli. PMID- 1749828 TI - Abuse of "BRON": a Japanese OTC cough suppressant solution containing methylephedrine, codeine, caffeine and chlorpheniramine. AB - 1. The paper describes the mental disturbances of 44 abusive cases of "BRON," an over-the-counter (OTC) cough suppressant solution containing methylephedrine, codeine, caffeine, and chlorpheniramine. 2. Major psychiatric symptoms observed included hallucinatory-paranoid state and affective disorder. There also were groups which exhibited a combination of the two states and abuse only. 3. The hallucinatory-paranoid state group had a relatively small BRON usage amount, short usage term and few withdrawal symptoms. The affective disorder group, in contrast, had large usage amount, longer usage term, and showed significant autonomic nerve disorders during withdrawal. These tendencies were seen more clearly in the mixed state group. 4. The hallucinatory-paranoid state group showed little or no physical dependence, while that of the affective disorder group was thought to be firmly established. Thus, in the former group, methylephedrine was considered the major behavior modifying drug, while in the latter, it was thought to be codeine. PMID- 1749829 TI - Buprenorphine responders: a diagnostic subgroup of heroin addicts? AB - 1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets. PMID- 1749830 TI - A nicotinic receptor antagonist enhances the hypothermic response to a muscarinic agonist. AB - 1. Chronic treatment with amitriptyline produces supersensitivity to the hypothermic effects of the muscarinic agonist oxotremorine. 2. Chronic treatment with amitriptyline also produces supersensitivity to the hypothermic effects of nicotine. 3. Oxotremorine and other naturally occurring muscarinic agonists are also nicotinic agonists. 4. Chronic treatment with amitriptyline produces time dependent and reversible supersensitivity to the hypothermic effects of nicotine. 5. The authors assessed the possibility that the development of supersensitivity to oxotremorine following chronic treatment with amitriptyline is related to an effect of this antidepressant on a nicotinic mechanism. 6. A nicotinic receptor antagonist would blunt (though not necessarily eliminate) enhanced sensitivity to the thermic effects of oxotremorine if the nicotinic effects of the latter are significant. 7. The simultaneous administration of mecamylamine (a peripherally and centrally active nicotinic receptor antagonist) greatly augments (rather than blunts) the hypothermic response to oxotremorine. 8. The data suggest that the oxotremorine may activate a nicotinic mechanism counterbalancing its effect on a muscarinic mechanism. 9. This is consistent with previously published reports that the activation of nicotinic and muscarinic mechanisms can exert opposite effects. PMID- 1749831 TI - Interleukin-1 potentiation of beta-endorphin secretion and the dynamics of interleukin-1 internalization in pituitary cells. AB - 1. This study demonstrates that human recombinant interleukin-1 (IL-1) stimulates beta-endorphin release and potentiates the secretion of beta-endorphin in both a mouse anterior pituitary cell line AtT-20 and rat pituitary cell cultures. 2. In pituitary cell cultures, prolonged treatment with phorbol ester had no effect on IL-1-induced beta-endorphin release, but abolished the potentiating effects of IL 1 on vasopressin-induced beta-endorphin secretion. 3. The enhancement of CRF stimulated beta-endorphin release by IL-1 was also reduced in normal pituitary cell cultures following depletion of protein kinase C. 4. The late IL-1-induced secretion of beta-endorphin does not require the continuous presence of the cytokine. 5. Incubation of monolayers with 125I-IL-1 alpha (10(-9) M) at 8 degrees C and then at 37 degrees C for various times revealed that IL-1 alpha was internalized. There was a progressive increase in the ratio of cytoplasmic to cell-surface-associated 125I-IL-1 alpha. 6. These results indicate that the IL-1 induced beta-endorphin release and its potentiation of beta-endorphin secretion involves internalization of this cytokine, perhaps via cell surface IL-1 receptors. PMID- 1749832 TI - Effect of ageing on melatonin synthesis induced by 5-hydroxytryptophan and constant light in rats. AB - 1. This paper describes the effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on pineal melatonin synthesis young and old rats. 2. 5-HTP itself increased pineal melatonin levels in old rats but did not change melatonin concentrations in young rats kept under 12 hr/12 hr light/dark conditions. 3. After continuous exposure to light for 72 hrs, 5-HTP induced a significant increase in melatonin levels in young rats but did not change the 5-HTP effect on melatonin in old animals. 4. These results are discussed in consideration of previous reports of altered beta-receptor up-regulation by light in old animals, and suggest that the age-related decrease in melatonin synthesis is not entirely related to changes of the enzymatic machine for melatonin synthesis. PMID- 1749833 TI - Naloxone effects on the visual evoked potentials recorded from the main and accessory visual pathways of the cat. AB - 1. The effects produced by repetitive i.v. administration of naloxone (1, 2 or 4 mg/kg) on the visual evoked potentials (VEPs) recorded along the main and accessory visual pathways were investigated in a modified "encephale isole" cat preparation. 2. Naloxone provoked a progressive amplitude enhancement and latency reduction of some components, depending on the structure analyzed, the dose used and the number of administrations applied. Electroretinogram (ERG) and N1-P1 VEP components of optic chiasm (OCh), lateral geniculate body (LGB) and visual cortex (VC) did not present significant changes. 3. Late-latency components (more than 200 msec) appeared in the VEPs of LGB and VC, mainly when 4 mg/kg were used. 4. Our results suggest that endogenous opioids have a modulatory role in the processing of sensory information at different levels of the visual system. PMID- 1749834 TI - Caring for depression in America: lessons learned from early findings of the medical outcomes study. AB - Research has documented that depressive disorders are a highly prevalent condition among adults in general population and patient samples and that these disorders are strongly associated with functional limitations. But data have not been available to compare the societal importance of depression to other major health conditions. In addition, although about one-half of persons with psychiatric disorders are believed to have their only contact with health care providers in the primary care sector, research findings suggest that depression often remains undetected and untreated in this secto; and there have been few data on how appropriateness of care for depression differs for patients in different health care delivery systems, or whose care is financed by prepayment or fee-for-service arrangements. As a result, it is not clear which health care systems should be promoted as providing appropriate care for this important psychiatric disorder. Data from the Medical Outcomes Study corroborate and strengthen the conclusion that depression is of considerable clinical and social importance in both outpatient medical and mental health specialty care sectors. Specifically, we have learned that depression is associated with as much limitation in multiple aspects of daily functioning and well-being as are most common chronic medical conditions. In addition, we have found that rates of detection of depressive disorder in the primary care sector are low and influenced by nonclinical factors such as type of payment for services. These findings increase the urgency of improving care for depression in the primary care sector, and of carefully evaluating how changes in the financing and organization of health care delivery systems affect the clinical care of psychiatric disorders. PMID- 1749835 TI - Research advances in consultation-liaison psychiatry. PMID- 1749836 TI - Uses of hypnosis in managing medical symptoms. PMID- 1749837 TI - The medical-psychiatric unit as a site for outcome research in dementia/depression syndromes. AB - The era of cross-sectional "snapshot" clinical epidemiology studies in consultation-liaison psychiatry, while still important, do not in themselves yield the critical outcome information needed to document both the clinical efficacy and cost-efficacy of timely psychiatric treatment of patients with concurrent medical-psychiatric illness. As consultation-liaison psychiatry has been plagued by problems regarding reimbursement for clinical services rendered and has only a few systematic outcome studies as yet documenting the effectiveness of treatment interventions, more prospective studies are desperately needed to confirm the value of our efforts. The era of proselytizing the virtues of consultation-liaison psychiatry is over, and as with every other area of psychiatric therapy, governmental policy makers and third party payors are appropriately demanding to see "proof" that our treatments are both clinically- and cost-effective. As may be seen from this brief overview of our research demonstrating the potential reversibility of disabling cognitive dysfunction in depressed medical-psychiatric patients and the efficacy of labetalol in decreasing cardiovascular complications from ECT in high risk medical patients, positive reports from clinical investigations that are strategically planned and implemented on specific populations form strong arguments for the clinical and probable cost efficacy of both consultation liaison psychiatry and medical-psychiatric units. PMID- 1749838 TI - Effectiveness of treatment for somatoform disorder patients. PMID- 1749839 TI - Research applications of a consultation-liaison psychiatry data base. PMID- 1749840 TI - The development of a randomized trial of consultation-liaison psychiatry trial in distressed high utilizers of primary care. PMID- 1749841 TI - Experimental study of psychiatric consultation for unrecognized psychopathology in general medical inpatients. PMID- 1749842 TI - The shift from outcome studies to epidemiological studies of specific medical illnesses in consultation-liaison psychiatry. PMID- 1749843 TI - Psychiatric aspects of renal dialysis and organ transplantation. PMID- 1749844 TI - Challenges, problems, and opportunities in consultation-liaison psychiatry research. AB - While consultation-liaison (C-L) psychiatry has blossomed as a psychiatric sub specialty, C-L research remains relatively underdeveloped. Individual case reports or else small series studies predominate. In contrast, relatively few studies are hypothesis-driven, experimental, or include design features such as blinding or randomization. Now that the field has matured, it is ready for such studies. Aside from the fact that developing fields require time to develop a research infrastructure, another reason for the lag in consultation-liaison research is the distraction with other issues such as the continuing debate between advocates of consultation vs liaison, competition with behavioral medicine practitioners, and the quest for formal sub-specialization status. Unless the development of a firm research base is equally emphasized, one worries about the longterm intellectual development of this important area. PMID- 1749845 TI - Value of MR imaging in evaluating focal fatty infiltration of the liver: preliminary study. AB - Focal fatty infiltration of the liver is a well-known entity that occasionally mimics metastatic disease on ultrasonographic (US) and computed tomographic (CT) scans and requires biopsy for diagnosis. To determine if high-field-strength magnetic resonance (MR) imaging might be useful in the differential diagnosis of the lesions, the authors compared US, CT, and MR findings in three patients with biopsy-proved fatty hepatic lesions. Areas of focal fatty infiltration were hyperechoic on US scans and had low attenuation on CT scans. No mass effect of the lesions on vascular structures or liver contours was observed, particularly on contrast material-enhanced CT scans. For all three patients, MR findings suggested the correct diagnosis by demonstrating focal high signal intensity on spin-echo T1- and T2-weighted images. On the basis of these preliminary findings, it appears that focal fatty infiltration of the liver may be differentiated from metastatic disease by means of high-field-strength MR imaging. PMID- 1749846 TI - State-of-the-art digital radiography. AB - Technologic advances in digital radiography have improved the ways in which radiographic images are acquired, displayed, transmitted, recorded, and archived. With computed radiography, performed with storage phosphor plates and interactive high-resolution workstations, radiation dose is reduced and repeat exposures necessitated due to technical errors are eliminated. Digital fluorography allows reductions in dose, procedure time, and film costs. These digital imaging modalities have been well accepted clinically and are equal in diagnostic accuracy to conventional methods. Teleradiology has advanced with the development of laser film digitization, fiberoptic networks, and dial-up circuit switching technology. Laser film printers yield improved hard copies of transmitted images, but further work is needed to faithfully reproduce the images displayed on high resolution work-stations. Although the capacity for archiving digital image data has increased (260,000 examinations or 23,500 Gbytes can be stored in a six-unit optical disc library), higher capacity storage media are needed. Further technologic advances in the speed of image transmission and storage capacity are anticipated. PMID- 1749847 TI - Radiology and computer science? PMID- 1749848 TI - Role of angiography in limb-tumor surgery. AB - Routine preoperative angiograms obtained in 97 consecutive patients with bone and soft-tissue tumors of the extremities were retrospectively reviewed to determine the role of angiography in surgical planning. Some degree of major vessel displacement was demonstrated in 51 patients. Encasement of major vessels, which precluded limb-salvage surgery, was seen in five of 76 bone tumors and in three of 21 soft-tissue tumors. All five patients with osteochondromas had associated vessel occlusion or compromise. For surgical planning, the demonstration of adequate anastomoses in the arches of the hands and feet is important, as branches of brachial and popliteal arteries may have to be sacrificed during limb tumor surgery. Angiographic findings indicated or supported the need for a vascular surgeon in five cases in this series. Preoperative angiography provides important information with regard to the status of the vasculature and therefore is essential in the management of bone and soft-tissue tumors of the extremities. PMID- 1749849 TI - CT of posterior mediastinal masses. AB - This article presents an algorithmic approach to the evaluation of posterior mediastinal masses seen with computed tomography (CT). CT remains the study of choice, since it not only can be used to help confirm the presence of these masses, but it also helps define the (a) location and extent of the lesion, (b) adjacent organ involvement, or (c) vascular involvement. Causes of posterior mediastinal masses include esophageal lesions, congenital or acquired vascular lesions, foregut cysts, intrathoracic goiters, mediastinal pseudocysts, fat containing tumors, adenopathy, neurogenic tumors, infectious spondylitis, and vertebral tumors. From the CT appearance of the lesion, one can often distinguish among the various masses and identify their origin and cause. This information enables patient triage and therapy to be expedited and, in most cases of posterior mediastinal masses, allows a correct diagnosis to be made solely on the basis of the CT examination. PMID- 1749850 TI - Developmental lymphatic disorders of the thorax. AB - Developmental disorders that involve the lymphatic channels of the thorax, although rare, are important and must be distinguished from the more common causes of chest masses or diffuse lung disease. There are four major types of developmental lymphatic disorders that affect the thorax: lymphangiectasis, characterized by congenital anomalous dilatation of pulmonary lymph vessels; localized lymphangioma, a rare and benign, usually cystic, lesion characterized by masslike proliferation of lymph vessels; diffuse lymphangioma, a proliferation of vascular, mainly lymphatic, spaces in which visceral and skeletal involvement are common; and lymphangioleiomyoma, which involves a haphazard proliferation of smooth muscle in the lungs and dilatation of lymphatic spaces. These characteristic findings can be seen with radiographic studies as well as with histologic evaluation. The discovery of one of these lymphatic disorders may prompt an investigation for associated congenital anomalies, including Noonan syndrome, asplenia, Gorham syndrome, and tuberous sclerosis. PMID- 1749851 TI - Typical, atypical, and misleading features in meningioma. AB - Meningiomas are the most common nonglial primary tumors of the central nervous system and the most common extraaxial neoplasms, accounting for approximately 15% of all intracranial tumors. They are usually benign neoplasms, with characteristic pathologic and imaging features. However, there are several important histologic variants of meningioma, and even a histologically typical meningioma can have unusual or misleading radiologic features that may not be suggestive of meningioma. The typical meningioma is a homogeneous, hemispheric, markedly enhancing extraaxial mass located over the cerebral convexity, in the parasagittal region, or arising from the sphenoid wing. Meningiomas may originate in unexpected locations such as the orbit, paranasal sinus, or ventricles or be entirely intraosseous (within the calvaria). Unusual imaging features such as large meningeal cysts, ring enhancement, and various metaplastic changes (including fatty transformation) can be particularly misleading. Because meningiomas are so common, the radiologist must be aware of their less frequent and uncharacteristic imaging features in order to suggest the correct diagnosis in cases that are atypical. PMID- 1749852 TI - Personal and public perceptions of radiation risks. AB - Risks often are accompanied by benefits, which are not attainable without incurring the risks. When a person voluntarily decides to take a risk, he or she assumes responsibility for the outcome, whether beneficial or adverse. The converse concerning involuntary risks is also true, with the result that many people oppose involuntary risks with their threat of adverse outcomes. Medical exposure to radiation can be perceived as both an involuntary and voluntary risk. In American culture, the entertainment and news media have contributed greatly to the public's abhorrence of radiation, radioactivity, and nuclear energy. Because people respond emotionally rather than intellectually to risk information, the risks of radiation exposure are best communicated by someone who is knowledgeable, is recognized as a health expert, is trustworthy, and has no conflict of interest but a stake in the community, such as a community physician. Such a spokesperson must respond first to perceptions of risks and underlying emotions, since use of only facts often fails to counteract fears. With trust established, a rational discussion of risks and benefits can begin. PMID- 1749854 TI - Career choices in radiology. PMID- 1749853 TI - Wrong turns on radiology's road of progress. PMID- 1749855 TI - Ultrasound case of the day. Cystic adenomatoid malformations of the lung, type II. PMID- 1749856 TI - General case of the day. Congenital bronchial atresia. PMID- 1749857 TI - Pediatric case of the day. Cystic lymphangioma (omental cyst). PMID- 1749858 TI - Color Doppler US of the scrotum. AB - Color Doppler ultrasonography (US) is an increasingly important tool in the evaluation of the scrotum, especially in acute scrotal disorders. With this modality, arterial flow is readily detected in the normal spermatic cord and testis but is not seen in the epididymis; venous flow is not seen anywhere in the normal scrotum. Scrotal inflammatory lesions appear as hypervascularity of the epididymis or testis, even though gray-scale findings may be normal or nonspecific. Testicular torsion is demonstrated by an absence or marked decrease in the number of visible vessels. Small tumors (less than 1.5 cm) are hypovascular, and larger tumors (greater than 1.5 cm) are hypervascular. The modality also demonstrates Valsalva maneuver-induced venous flow augmentation in varicoceles and altered flow in testicular tumors. Color Doppler US allows for evaluation of morphologic findings and perfusion and enables accurate diagnosis of most scrotal disorders. PMID- 1749859 TI - Imaging of intra- and extraabdominal desmoid tumors. AB - Desmoid tumors are characterized by proliferation of fibroblastic cells that arise from the fascia or aponeurosis of muscle. They are most commonly found in the abdomen of adults, arising from the anterior abdominal wall, mesentery, or retroperitoneum. At sonography, desmoids have variable echogenicity, with smooth, well-defined margins. On contrast-enhanced computed tomographic scans, the tumors are generally high attenuation (relative to muscle) and have either ill- or well defined margins. At magnetic resonance imaging, desmoids have low signal intensity relative to muscle on T1-weighted images and variable signal intensity on T2-weighted images. There are no specific imaging features to distinguish desmoid tumors from other solid masses. The diagnosis of desmoid tumor should be considered in patients with an abdominal mass, a history of abdominal surgery or injury, or Gardner syndrome. PMID- 1749860 TI - Diagnostic pitfalls in abdominal CT. AB - Many factors result in suboptimal performance of abdominal computed tomography (CT) or inaccurate interpretation of the images. Improper technique, observers' errors, and lack of clinical information are major contributors to misdiagnoses. Because of inadequate oral administration of contrast material, normal structures (eg, bowel) may remain unopacified and simulate tumors. Repeat scanning with additional contrast material and sodium bicarbonate, at selected levels, and perhaps with changes in patient position often reveals the true nature of pseudotumors in the gastrointestinal tract. Dynamic CT of the liver, performed during contrast material injection, yields the best results. Occasionally, reconstruction of axial images in coronal or sagittal planes helps delineate normal sectional anatomic variations of the diaphragm and liver and avoid misdiagnosis of pseudomasses. Volume averaging can cause problems when the section thicknesses are larger than the lesions (eg, small hepatic cysts) or structures are very close (eg, kidney and spleen); repeat CT with thinner sections is needed to obtain accurate attenuation values or delineate normal anatomic relationships. The gallbladder, spleen, and pancreas can change position due to prior surgery and raise suspicion of a mass unless clinical history is known. Familiarity with these and other pitfalls described herein should lead to accurate interpretation of CT scans. PMID- 1749861 TI - [Inflammatory aspects in bronchial asthma]. PMID- 1749862 TI - [New insights on and diversity of causative allergens for bronchial asthma]. PMID- 1749863 TI - [Epidemiology and natural history of bronchial asthma--prognosis of child-onset asthma in adulthood]. PMID- 1749864 TI - [Clinical role of antiallergic drugs in the treatment for bronchial asthma]. PMID- 1749865 TI - [Mortality from asthma]. PMID- 1749866 TI - [Software contest: aims, procedures and results]. PMID- 1749867 TI - [Electrophysiological effect of verapamil on human atrium]. AB - To investigate the effect of verapamil on atrial vulnerability, the following measurements were performed before and after the intravenous administration of verapamil (0.15 mg/kg) in 10 subjects with paroxysmal atrial fibrillation (Paf), and 10 subjects without Paf (non-Paf). During the sinus rhythm, 1) intra /interatrial conduction time (Intra-/Inter- ACT); the initial deflection of high right atrium (HRA) to that of His bundel/coronary sinus were measured. After 8 consecutive HRA stimuli (A1), premature stimulus (A2) was introduced by shortening the coupling interval (A1A2) and we measured 2) conduction delay zone (CDZ); the zone of A1A2 with the prolongation of Inter-ACT, 3) % maximum atrial fragmentation (%MAF); % maximum value of the ratio of HRA activity width at A2 (Awt) against that at A1 (Awc), 4) fragmented atrial activity zone (FAZ); the zone of A1A2 with % value of Awt/Awc more than 150%,5) repetitive atrial response (RAR); more than 2 atrial activities which occur in response to A2. (6) right atrial effective refractory period (RAERP). Verapamil significantly shortened CDZ and %MFA, slightly lengthened RAERP, and had RAR disappear in Paf, while it did not effect any indices significantly in non-Paf. We concluded that verapamil could reduce atrial vulnerability in Paf due to blocking of atrial conduction delay mediated by slow response fibers. PMID- 1749868 TI - [Impairment of left ventricular diastolic function during the asymptomatic period in vasospastic angina patients without significant coronary stenosis]. AB - We examined whether recurrent transient ischemia may effect left ventricular systolic and diastolic function or not. Left ventricular systolic and diastolic function during the asymptomatic period was studied by gated radionuclide ventriculography (RNV) in 25 patients with vasospastic angina (VA) who had no significant coronary stenosis, in 25 patients with effort angina (EA), and in 20 controls (C). There was no significant difference among patients in all three groups in regards to systolic indices (Ejection Fraction, Peak Ejection Rate). But diastolic indices (Peak Filling Rate, Time to Peak Filling Rate, 1/3 Mean Filling Rate, 1/3 Filling Fraction) were impaired not only in patients with EA but also in patients with VA. The treatment with nitrates and/or Ca antagonist for 6-24 months did not bring about any changes in these data concerning systolic and diastolic function in patients with VA. Thus, it is suggested that the diastolic function is impaired in patients with VA even during the asymptomatic period, though systolic function remains normal. Recurrent transient ischemia may cause irreversible myocardial injury. PMID- 1749869 TI - [Mitral flow dynamics in patients with hemodialysis: assessment with pulsed Doppler echocardiography]. AB - We investigated transmitral flow dynamics before (B) and after (A) hemodialysis (HD). Pulsed Doppler echocardiography was performed in 15 patients (10 males and 6 females, with a mean age of 51) with neither valvular disease nor heart failure. After HD, systolic and diastolic pressure declined significantly to [156 +/- 27----135 +/- 24mmHg (p less than 0.01) and 84 +/- 16----75 +/- 15mmHg (p less than 0.02)] respectively. However, heart rate did not change. Doppler derived indexes were peak early filling velocity (E), peak filling during atrial contribution (A), early filling time velocity integral (IE), atrial time velocity integral (IA), and percent atrial contribution [IA/(IE + IA) x 100] (%A) There was a positive correlation between E and peak systolic stress (r = 0.437, p less than 0.05). Conclusion; In HD, early diastolic filling is dependent on preload. It is necessary to consider preload when diastolic function is assessed. PMID- 1749870 TI - [Coronary flow reserve and stenosis as the determinant of exercise capacity in patients with stable effort angina]. AB - The coronary flow reserve was evaluated in 33 patients with stable effort angina and single vessel disease of the left anterior descending artery. We used a catheter-tip Doppler flow probe with injection of contrast media to the vessel in order to induce so-called reactive hyperemia. The reactive change was used as an index of the flow reserve of the coronary artery. In 15 patients out of 33, PTCA was performed and the change in the coronary flow reserve was evaluated. There was a good correlation between the coronary flow reserve and the exercise capacity in the treadmill ECG exercise test. As theoretically expected, the exercise capacity was determined by the coronary flow reserve. There was a poor correlation between the degree of stenosis shown in coronary arteriography and the coronary flow reserve. The degree of stenosis did not relate with the exercise capacity. The coronary flow reserve was increased with the procedure of PTCA. Though the patho-anatomic findings in coronary angiography give us important information to evaluate patients with ischemic heart disease, we concluded that these findings were still insufficient to allow us to estimate the flow reserve in the coronary artery. The exercise capacity did not relate well with the degree of stenosis. PMID- 1749871 TI - [Tolerance to a sustained release form of isosorbide dinitrate: comparison between 20 mg four times and 40 mg twice-daily administrations]. AB - Attenuation of antianginal effects of oral isosorbide dinitrate in a sustained release from (ISDN-SR) were studied using the treadmill exercise test in eleven patients with stable exertional angina and a positive exercise test. We compared the four-time-daily administration of 20 mg with a twice-daily regimen of 40 mg for 10 days using the double-blind, crossover method. On the 1st day of the administration, with both regimens, the treadmill walking time, the time to 1mm and 2mm ST depression, and several hemodynamic parameters increased significantly. These improvements were reduced gradually on day 5 and day 10 after the administration. In the comparison between the four-time-daily and two time-daily regimens, the former application showed clearer antianginal and hemodynamic effects than the latter regimen, but these effects were attenuated more markedly in the four-time daily administration. With both dosage regimens, the plasma ISDN concentrations increased gradually. With the long-term four-time daily regimen, the time-to-time changes of the ISDN concentration were smaller each day. These data suggest that tolerance to oral ISDN-SR exists even if it is applied only two time daily, but its degree is less than when a four-time-daily dose in administered. PMID- 1749872 TI - [Two cases of atrial septal defect diagnosed by two-dimensional Doppler echocardiography: comparison with other methods for detecting atrial septal defect]. AB - We describe two cases of atrial septal defect(ASD) diagnosed by chance with two dimensional Doppler echocardiography(2DD) which was carried out for another purpose. There were no findings characteristic of ASD such as systolic murmurs in the pulmonary area, incomplete right bundle branch block pattern on electrocardiograms, increased hilar shadow on chest films or increased right ventricular chamber diameter in two-dimensional echocardiography. However, the 2DD showed blood flow crossing through the atrial septum. Cardiac catheterization confirmed the presence of a small ASD. ASD diagnosed by 2DD alone without other classical characteristic signs of ASD indicates that the ASD is small and clinically insignificant as it is with Doppler valvular heart disease. PMID- 1749873 TI - [A case of Behcet's disease complicated with acute myocardial infarction]. AB - A 23-year-old-man was admitted to our department complaining of chest oppression. He had had a diagnosis of intestinal-Behcet because of a 7-year history of recurrent oral and genital ulcers, arthritis, cutaneous folliculitis and ulcer in the ileocecal region. Cardiac catheterization revealed total occlusion at the proximal portion of the left anterior descending artery (LAD) without aneurysm formation at other coronary trees. During medical follow-up, this case showed vasospastic angina probably associated with active coronary vasculitis. The incidence of vascular involvement in the total number of cases of Behcet's disease reported in the literature is 3.6-7.7%. Overall, thrombophlebitis and arterial aneurysm formation is relatively common and frequently reported in cases of vasculo-Behcet. Our case demonstrated the following uncommon pattern as vasculo-Behcet; 1) initial clinicopathologic manifestation at the coronary artery without any other vascular lesion, 2) abrupt total occlusion (clear cut lesion) at LAD, 3) complication of vasospastic angina, which has not yet been reported in medical literature. PMID- 1749874 TI - [A case of adult type of anomalous origin of left coronary artery from pulmonary artery--with a referential consideration to the disease in Japan]. AB - A case of a 33-year-old man with anomalous origin of the left coronary artery from the pulmonary artery (ALCP) was reported with a referential consideration to the adult type of ALCP previously reported in Japan. The patient visited our hospital for further examination of cardiac murmur detected on a mass physical checkup. He was found to have a continuous murmur, the loudest in the left sternal border of 3rd intercostal space, and developed evidence of ischemia during the exercise stress test in the ECG leads of L2, L3, aVF, and V2 through V6. In addition, studies using echocardiography and color Doppler echocardiography detected a hypertrophied intraventricular septum and a pattern of turbulent blood flow in the proximal pulmonary artery. Cardiac catheterization and aortography proved the existence of ALCP with a markedly developed collateral circulation from the right coronary artery to the left coronary artery. After surgical restoration by ligating the anomalous opening of the left coronary artery, and by bypass grafting to the left coronary artery, it was clear that dilation and kinking of the right coronary artery was lessened and hypoperfusion in the anterior left ventricular wall was improved. As far as we know, this case is the 35th of adult type ALCP reported in our country. Results from this case and others suggest that early detection and therapy for adult type ALCP is important from the point of view preventing ischemic progression, and indicate that restoration by ligation and bypass grafting may be one of the effective surgical procedures for ALCP. PMID- 1749875 TI - [What is your diagnosis? Tension headache - basilar migraine?]. PMID- 1749876 TI - [Substitution therapy in alpha 1-protease inhibitor deficiency (alpha 1 antitrypsin deficiency)]. AB - Deficiency of alpha 1-protease inhibitor is a dominant autosomally inherited error of metabolism leading to destruction of alveolar septa by proteolytic enzymes mainly released by neutrophils often before the fifth decade. Diagnosis and determination of phenotype are achieved by serologic tests. Affected individuals have to be informed about the accelerated evolution of the lung disease by smoking and the possibility of therapy by substitution. The latter aims at maintenance of anti-proteolytic serum levels compatible with arrest of emphysema by weekly to monthly injections of human alpha 1-protease inhibitor as we illustrate with a case-report. In the future antiprotease produced by gene technology, the application via aerosols or an infection of endothelial cells with viruses transferring genes for antiprotease may be possible. PMID- 1749877 TI - [New viewpoints on old cases: pneumonia. 1841]. AB - In this third presentation of reviewed old case histories a lecture by the famous clinician Schoenlein held in 1841 at the Charite on a patient with pneumonia is commented on. This case is in many ways instructive and interesting. The lecture at first reveals the numerous diagnostic difficulties in medicine 150 years ago and then demonstrates the great innovation brought to physical examination by ausculatation introduced to the clinic by Schoenlein against great opposition. For the first time the clinical diagnosis of pulmonary lesions had become possible whereby the diagnostic criteria for pneumonia obtained by auscultation and percussion were already precisely established. Furthermore the utilized therapeutic measures are in part still applicable. This impressive didactic demonstration reveals why Schoenlein was regarded as the most important clinical teacher of his time introducing modern scientific medicine. PMID- 1749878 TI - [Maculopapular rash, pruritus, upper abdominal pain, attacks of dizziness]. AB - A 48 year old male patient presented with maculopapular rash, pruritus, peptic ulcer disease and attacks of headache and vertigo. Rubbing of the cutaneous lesions led to urticarial whealing which is indicative of abnormal mast cell proliferation in the cutis. Histologic evidence of abnormal mast cell proliferation in biopsy specimens of skin and bone marrow led to the diagnosis of systemic mastocytosis. Treatment with H1 and H2 receptor antagonists was started. PMID- 1749879 TI - [A case from practice (231). Erythema nodosum of unclear origin]. PMID- 1749880 TI - [What is your diagnosis? Multiple sclerosis]. PMID- 1749881 TI - [Gastrospirillum hominis--a new bacterium in chronic gastritis]. PMID- 1749882 TI - [Primary volvulus of the small intestines in adults]. AB - In our area, small bowel volvulus is a sporadic form of mechanical intestinal obstruction. Diagnostic problems may occur. The clinical presentation is that of an acute abdomen. The cause of symptoms may be due to narrowing of the bowel itself, or strangulation of the blood supply, or both. The types (primary and secondary) and incidence of small bowel volvulus are age-related and demonstrate astonishing geographical differences. Goals for treatment of small bowel volvulus should include physician awareness and accurate workup of this uncommon diagnosis. PMID- 1749883 TI - [Experiencing and coping with the diagnosis and therapy of a malignant bone tumor and the survival time afterwards]. AB - Six patients who had been treated for osteosarcoma of the lower extremity report their experience and how they mastered diagnosis and therapy as well as the time thereafter. They give information regarding especially the following points: psychological stress during different phases of their disease, aspects of the information they received during treatment, how they felt during therapy and how and where they have received support, wishes, etc. RESULTS: In order to master the disease as well as the sequelae they need sufficient time and opportunities to express their feelings to others and sufficient understandable informations about examinations, therapy and prognosis. There are large variations in how the individual patient responds to the threat by the disease. The whole period of time with repeated hospitalizations that extends over about one year in retrospect has been judged to be very burdening. Most of the patients feel to be strongly challenged during chemotherapy; physically, they are reduced, are oversensitive and need sensitivity and support by the persons taking care of them. The informations given by the patients allow us to improve treatment and support of patients in the future. PMID- 1749884 TI - [A case from practice (233). Eosinophilic myalgia syndrome]. PMID- 1749885 TI - [Phlebo-varicography in chronic venous insufficiency of the lower limbs]. PMID- 1749886 TI - [Chronic venous insufficiency: clinical functional tests and non-invasive paraclinical studies]. PMID- 1749887 TI - [Superficial thrombophlebitis]. PMID- 1749888 TI - [Nutritional support of the patient with AIDS]. PMID- 1749889 TI - [12 theses on drug abuse]. PMID- 1749890 TI - [Accident insurance, CNA and medical corps]. PMID- 1749891 TI - [Role of the medical consultant in Sick Fund cases]. PMID- 1749892 TI - [Medical secrecy]. PMID- 1749893 TI - [Intercantonal Office for Drug Control. Its history, activities, current problems]. PMID- 1749894 TI - [Tasks of the Federal Office of Social Security in the field of health]. PMID- 1749895 TI - [The Swiss health system. Potentials, problems and perspectives]. PMID- 1749896 TI - [Venous insufficiency: review of anatomy, physiopathology and epidemiology. Definition of varices]. PMID- 1749897 TI - [Clinical and cutaneous aspects of chronic venous insufficiency]. PMID- 1749898 TI - [Ambulatory treatment of chronic venous insufficiency]. PMID- 1749899 TI - [Diagnosis of deep venous thrombosis of the lower limbs: the role of clinical and paraclinical methods]. PMID- 1749900 TI - [Phlebography in deep venous thrombosis of the lower limbs]. PMID- 1749901 TI - This nurse recalls a leeching case long ago. PMID- 1749902 TI - A plea to remember the constant need for organ donations. PMID- 1749903 TI - FDA makes AIDS drug available before tests are complete. PMID- 1749905 TI - Do nurses know the fact about AIDS? PMID- 1749904 TI - Voice your opinions about the mandatory AIDS testing bills. PMID- 1749906 TI - New estimates on the cost of treating HIV. PMID- 1749907 TI - When your supervisor hands you the reins. PMID- 1749908 TI - The best fetal monitor? Maybe it's you. PMID- 1749909 TI - Cardiac assessment. PMID- 1749910 TI - RN pins down nursing history. PMID- 1749911 TI - Pediatric i.v. therapy: soothing the patient. PMID- 1749912 TI - Pediatric i.v. therapy: starting the line. PMID- 1749913 TI - A simple way to treat simple pneumothorax. PMID- 1749914 TI - One way up. In tandem with a doctor. PMID- 1749915 TI - Pressure ulcer update. PMID- 1749916 TI - If you're asked to be an expert witness. PMID- 1749917 TI - Vitamins, minerals, and the common cold. PMID- 1749918 TI - Oxygen therapy helps when treating reimplanted limbs. PMID- 1749919 TI - Dietary antigen handling by mother and offspring. AB - Sows were fed ovalbumin (OvA) as a novel protein antigen either throughout gestation and lactation (G + L) or during lactation only (L). This resulted in a significant uptake of OvA into blood, colostrum and milk along with a specific IgG response. In piglets from the G + L group, OvA and antibodies to OvA were detected in serum after ingestion of colostrum. In a large proportion of these piglets OvA was still detected at 3 weeks of age. In the L group a significant proportion of the piglets responded to OvA whilst still suckling their mother. At 3 weeks of age all piglets were weaned onto an egg-based diet. A similar uptake of OvA was seen in all piglets but there was no response to OvA in the G + L piglets. In piglets from sows fed only during lactation, however, a rapid IgG anti-OvA response and signs of diarrhoea were seen. The results suggest that factors of immunological importance are passed over from mother to offspring and it is proposed that immunological experience of dietary antigens by the mother is important for a 'safe' tolerance induction in her offspring. PMID- 1749920 TI - Separation of leucocytes: improved cell purity by fine adjustments of gradient medium density and osmolality. AB - This paper briefly reviews commonly used procedures for separation of mononuclear cells (MNC) and granulocytes from human blood with X-ray contrast media as gradient material, and also presents new and modified procedures for leucocyte preparation. Standard techniques for human blood do not always yield satisfactory results with blood from other species. In general pure MNC are easily obtained (top fraction), but often the granulocyte fraction has a low purity, due to contamination with MNC that move to the bottom during centrifugation and contaminate the granulocyte suspension. Obviously the density distribution of MNC differs between species. However, the separation can be improved by fine adjustment of gradient medium osmolality. For this purpose we have used Nycodenz, a non-ionic X-ray contrast medium. A favourable property of Nycodenz solutions is that the osmolality and density can easily be varied over a broad range. The cells react promptly to a change of medium osmolality. In hypertonic medium the cells expel water, shrink, their density increases and they sediment faster, in spite of a smaller radius. Further, the cells may pass what was initially a density barrier. A hypotonic environment has the opposite effect. In the present work we were able to show that a slight change of medium osmolality clearly improved different techniques for separation of leucocyte subgroups. For instance, the Isopaque-Ficoll (IF) technique consistently yielded MNC and granulocytes of high purity with human blood. However, with blood from rabbits, rats and mice the granulocyte suspensions were contaminated by 40-60% MNC. By utilizing Nycodenz, and lowering the osmolality by 10-12 per cent (at constant density--1.077 g/ml) we obtained satisfactory separation of MNC as well as granulocytes with blood from these species. A problem in the routine separation of granulocytes (IF) is a high contamination of erythrocytes (2-5 per cell) in the granulocyte suspension. With a two-layer technique with Nycodenz solutions of different densities it was possible to separate granulocytes almost devoid of erythrocytes, after proper adjustment of osmolality. By appropriate combination of density and osmolality, Nycodenz was a suitable gradient material in other separation procedures as well, e.g. the separation of monocytes and mast cells. To facilitate the use of Nycodenz as a versatile gradient material, a computer program providing recipes for various Nycodenz solutions is included as an appendix. PMID- 1749921 TI - Enhancement of IgE synthesis in the human myeloma cell line U-266 with an IgE binding factor from a human T-cell line. AB - An IgE-binding factor(s) (IgE-BF(s] was partially purified from the supernatant of human HTLV-II carrying T-cell line MO. This IgE-BF(s) was shown to increase the IgE synthesis in the human myeloma cell line U-266, but did not affect its viability or growth. The effect of the IgE-BF(s) was dose-dependent and selective for IgE protein synthesis as beta 2-microglobulin synthesis in the U-266 and the immunoglobulin production in the U-1958 IgG-secreting human myeloma cell line were unaffected. The IgE-BF(s) increased the production of the epsilon heavy chain but not the lambda light chain production. The IgE-BF(s) was distinct from IL-1 beta, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, -beta, -gamma, M-CSF, and fragments of CD23. PMID- 1749922 TI - Spectral analysis of the renal sympathetic neurogram during left ventricular assistance. AB - To assess the effect of left ventricular assistance on cardiac-related sympathetic nerve activity, renal sympathetic nerve activity was analysed using power spectrum and coherence function. Our TH-7B pneumatically driven sac type Ventricular Assist Device (VAD) was used in the acute experiment of 7 adult mongrel dogs. VAD were inserted between the left atrium and the descending aorta as left heart bypass. RSNA was detected by use of the bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were measured at the cardiac rhythm and VAD pumping rhythm. Before the left ventricular assistance, coherence at the cardiac rhythm and the pumping rhythm were 0.62 +/- 0.15, 0.23 +/- 0.18 (mean +/- SD), respectively. With the VAD pumping, these values became 0.09 +/- 0.05, 0.53 +/- 0.20, respectively. These results indicate that arterial pressure wave which was created by the VAD assistance contributed to the post ganglionic sympathetic activity. PMID- 1749923 TI - Development and evaluation of the vibrating electromagnetically-driven artificial heart. AB - An vibrating electromagnetically driven univalved artificial heart was newly developed in our team. The fluid mechanical, hematological, and hemodynamical properties of this pump was evaluated in the moc circulation and animal experiments using adult goats. This vibrating electromagnetic (VEM) pump could generate more than 101/min with 10 Hz vibration, and could obtain the 2 kinds of flow and pressure patterns, such as constant peak and periodical peak patterns. The values of free Hb showed within acceptable values. We concluded that this pump is useful for totally implantable artificial heart. PMID- 1749924 TI - TH-7B pneumatically driven sac-type ventricular assist device and drive system. AB - TH-7B pneumatically driven sac-type ventricular assist device and drive system including automatic control system were developed and evaluated in the chronic animal experiments. The blood-contacting surfaces of the blood pump are coated with either Cardiothane or Cardiomat. In the chronic experiments using adult goats, only one of fifteen goats showed sudden thrombus formation after 34 pumping days. No gross findings of thrombus formation were observed in any of the cases, except for a thin circular thrombus at the junction of the connectors and the sac of the blood pump. These results suggest that antithrombogenicity of this system was satisfactory for clinical use. PMID- 1749925 TI - Development of the total artificial heart control system. AB - Sympathetic neurogram is potentially useful for the real time total artificial heart (TAH) control system. In this study, we used sympathetic tone and hemodynamic derivatives to prospect the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as the parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was also utilized as the parameter of the sympathetic tone. Equation which prospect the following cardiac output was calculated using the multiple linear regression analysis of the time series data in adult mongrel dogs. A significant correlation was observed between the prospective and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system. PMID- 1749926 TI - Coherence function between sympathetic neurogram and arterial pulse wave in animal with total artificial heart. AB - To assess the influence of the total artificial heart replacement on autonomic nervous system, sympathetic neurogram was analyzed by power spectrum and coherence function. Two pneumatically driven sac-type ventricular assist devices were implanted as biventricular bypass (BVB) in adult mongrel dogs. After the BVB pumping, natural heart was electrically fibrillated to constitute the BVB type TAH model. Renal sympathetic nerve activity (RSNA) was recorded using the bipolar electrode attached to the left renal sympathetic nerve. RSNA was amplified and integrated by the use of R-C integrator. Power spectra of the RSNA and the values of squared coherence between the arterial pressure waveform and the RSNA were calculated by the computer system. In animal with TAH, coherence at the cardiac rhythm frequency was decreased, and coherence at the TAH pumping rhythm frequency was increased. These results indicate that the arterial pulse wave which was observed in TAH animal contributed to sympathetic neurogram. PMID- 1749927 TI - Clinical application of the ventricular assist devices in Japan. AB - From 1980 to March in 1989, there were 177 clinical application of ventricular assist device in Japan. Original diseases were 50% ischemic heart disease and 37% valvular disease. Duration of assistance ranged from one hour to 70 days. Thirty one cases weaned from ventricular assistance and 11 cases became long-time survivors. PMID- 1749928 TI - Importing biological materials. PMID- 1749929 TI - Negative reinforcement. PMID- 1749930 TI - David Baltimore's final days. PMID- 1749931 TI - Hepatitis A vaccine shows promise. PMID- 1749932 TI - MRC denies blocking access to genome data. PMID- 1749933 TI - The energy landscapes and motions of proteins. AB - Recent experiments, advances in theory, and analogies to other complex systems such as glasses and spin glasses yield insight into protein dynamics. The basis of the understanding is the observation that the energy landscape is complex: Proteins can assume a large number of nearly isoenergetic conformations (conformational substates). The concepts that emerge from studies of the conformational substates and the motions between them permit a quantitative discussion of one simple reaction, the binding of small ligands such as carbon monoxide to myoglobin. PMID- 1749934 TI - Heterogeneous amino acids in Ras and Rap1A specifying sensitivity to GAP proteins. AB - Guanosine triphosphatase (GTPase) activity of Ras is increased by interaction with Ras-GAP (GTPase-activating protein) or with the GAP-related domain of the type 1 neurofibromatosis protein (NF1-GRD), but Ras is not affected by interaction with cytoplasmic and membrane forms of Rap-GAP; Rap1A, whose effector function can suppress transformation by Ras, is sensitive to both forms of Rap GAP and resistant to Ras-GAP and NF1-GRD. A series of chimeric proteins composed of portions of Ras and Rap were constructed; some were sensitive to Ras-GAP but resistant to NF1-GRD, and others were sensitive to cytoplasmic Rap-GAP but resistant to membrane Rap-GAP. Sensitivity of chimeras to Ras-GAP and cytoplasmic Rap-GAP was mediated by amino acids that are carboxyl-terminal to the effector region. Residues 61 to 65 of Ras conferred Ras-GAP sensitivity, but a larger number of Rap1A residues were required for sensitivity to cytoplasmic Rap-GAP. Chimeras carrying the Ras effector region that were sensitive only to Ras-GAP or only to cytoplasmic Rap-GAP transformed NIH 3T3 cells poorly. Thus, distinct amino acids of Ras and Rap1A mediate sensitivity to each of the proteins with GAP activity, and transforming potential of Ras and sensitivity of Ras to Ras-GAP are at least partially independent properties. PMID- 1749935 TI - Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. AB - The cDNA for human gamma-glutamyl carboxylase, which accomplishes the post translational modification required for the activity of all of the vitamin K dependent proteins, was cloned. The enzyme is a 758-residue integral membrane protein and appears to have three transmembrane domains near its amino terminus. The hydrophilic COOH-terminal half of the carboxylase has 19.3 percent identity with soybean seed lipoxygenase. Expression of the cloned cDNA resulted in an increase in carboxylase activity in microsomes of transfected cells compared to mock-transfected cells. PMID- 1749936 TI - Dopaminergic and ligand-independent activation of steroid hormone receptors. AB - The current view of how steroid hormone receptors affect gene transcription is that these receptors, on binding ligand, change to a state in which they can interact with chromatin and regulate transcription of target genes. Receptor activation is believed to be dependent only on this ligand-binding event. Selected steroid hormone receptors can be activated in a ligand-independent manner by a membrane receptor agonist, the neurotransmitter dopamine. In vitro, dopamine faithfully mimicked the effect of progesterone by causing a translocation of chicken progesterone receptor (cPR) from cytoplasm to nucleus. Dual activation by progesterone and dopamine was dissociable, and a serine residue in the cPR was identified that is not necessary for progesterone dependent activation of cPR, but is essential for dopamine activation of this receptor. PMID- 1749938 TI - Schonlein-Henoch syndrome in adults and children. AB - Sixty-one patients (15 adults and 46 children) with Schonlein-Henoch syndrome (SHS) were seen at the Hadassah University Hospital over the last 20 years. The presentation, clinical course, and prognosis of these patients were studied. The disease course was generally similar in children and adults, except for the epidemiological background and the pattern of skin and joint involvement. In these nonselected patients, the disease was self-limited, and progressive renal failure was not found. The long-term prognosis was excellent for both adults and children. PMID- 1749937 TI - Intracellular signaling by 14-hydroxy-4,14-retro-retinol. AB - In mammals, retinol is the precursor for retinoids, which affect various aspects of morphogenesis and development. However, B lymphocytes, although retinol dependent, do not use retinoic acid as mediator. Retinol is metabolized by B lymphocytes and other cell lines to optically active 14-hydroxy-4,14-retro retinol; it is this compound that mediates the growth control. Thus another second messenger molecule, in addition to retinoic acid and retinal, is derived from retinol. PMID- 1749939 TI - Treatment of the eosinophilia-myalgia syndrome. AB - The eosinophilia-myalgia syndrome (EMS) is a unique entity associated with products that contain L-tryptophan (L-trp). Studies of the underlying etiopathogenic processes are underway. EMS is a distinct syndrome, but shares features with eosinophilic fasciitis and other variants of systemic sclerosis. A wide spectrum of clinical manifestations has been described, but there is no consensus regarding treatment. We report the clinical and laboratory features of 12 patients. All were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics with transient or minimal effect. Two received D-penicillamine (DP) and colchicine, with minimal improvement; one had no response to azathioprine (AZA). Eleven received corticosteroids and had improvement of general symptoms, arthralgias, arthritis, myalgias, skin changes, eosinophilia, and leukocytosis. Nevertheless, all but the latter two findings recurred when corticosteroids were tapered. Seven patients who were unresponsive to the former treatments received low-dose pulse oral methotrexate. Six exhibited continued improvement after a mean follow-up of 4.5 months, with good drug tolerance. Corticosteroids were tapered and, in some instances, discontinued without relapse or complications. One patient improved but later died of aspiration pneumonia. We conclude that methotrexate (MTX) is a therapeutic alternative for patients with severe or refractory EMS. PMID- 1749940 TI - The rheumatoid hand: orthotics as preventative. AB - The treatment of hand disease in patients with rheumatoid arthritis (RA), with focus on rehabilitation and splinting, is discussed. A review of the data on splinting of hands in RA is included, as is a review of methods for evaluating hand function and staging RA. Recommendations are made for splinting early in the disease course and prior to surgery, rather than late in the course of RA, in an effort to minimize contractures. PMID- 1749941 TI - Variables associated with decreased survival in systemic lupus erythematosus. AB - Fifty-one deaths occurred among 310 patients with systemic lupus erythematosus (SLE) observed for 1,234 patient-years. Twenty-one of 97 entry variables at first clinic visit were associated with an increased risk of mortality. When corrected for multiple comparisons, the only risk factor that retained statistical significance was systolic blood pressure. Each millimeter unit increase in systolic blood pressure corresponded to a 2% increase in mortality risk. Stepwise covariance and recursive partitioning analyses tended to identify nonspecific prognostic variables, rather than the classic serological and diagnostic features of SLE. These data suggest that hypertension is a more significant risk factor for mortality in SLE than the more specific measures of disease severity. PMID- 1749942 TI - Septic arthritis in heroin addicts. AB - Over a 6-year period (1982 to 1988), 36 episodes of septic arthritis were diagnosed in 35 heroin addicts from Barcelona, Spain. Thirty (86%) were men and five (14%) were women, with a mean age of 24 years (range, 14 to 39). Twenty-nine episodes (80%) were monoarticular and seven (20%) were oligoarticular. The sacroiliac (16 cases), sternoclavicular (8), hip (5), and shoulder (4) joints were most frequently infected. Staphylococcus aureus and Pseudomonas aeruginosa were the etiological agents in 75% and 11% of episodes, respectively. Response to antibiotic treatment was good in 32 cases (90%), eight patients needed surgical drainage, and none died. We conclude that septic arthritis in heroin addicts localizes predominantly in axial joints. In our geographic area, infection with S aureus is more frequent than with gram-negative rods such as P aeruginosa or Serratia marcescens, which are most frequently found in reports from the United States. PMID- 1749943 TI - Chiral stereoisomeric molecules in the treatment of arthritis. AB - Pharmacokinetic and pharmacodynamic properties of drugs and their ultimate therapeutic effects are often significantly influenced by interactions between the geometry of host receptors, host enzymes, and the three-dimensional structure of drugs. Drug molecules that are mirror images of each other are chiral stereoisomers, and such chiral isomer compounds are commonly used as therapeutic agents by rheumatologists either as racemates (mixtures of chiral isomers) or as pure stereoisomers. Understanding and using such stereoisomeric drugs may lead to lower risks of drug toxicity, better therapeutic indices, and newer approaches for the treatment of articular disorders. A review of the properties of these special isomers is presented, and their therapeutic advantages are discussed. PMID- 1749944 TI - The place of methotrexate in the treatment of rheumatoid arthritis. Introduction. PMID- 1749945 TI - A double-blind comparison of parenteral methotrexate and parenteral gold in the treatment of early erosive rheumatoid arthritis: an interim report on 102 patients after 12 months. AB - One hundred two patients with active erosive rheumatoid arthritis (RA) without malalignment or deformities (median disease duration, 14 months) entered a double blind, randomized study to compare the effects of 50 mg gold sodium thiomalate (GST) with 15 mg methotrexate (MTX) administered intramuscularly for 12 months. Roentgenograms of hands, wrists, and forefeet were taken at baseline and after 6 and 12 months, and 32 joints were evaluated according to Larsen. Sixteen of 50 patients in the MTX group were withdrawn; one patient in the MTX group died of cerebral bleeding that was not related to treatment. Thirty-four GST patients and 44 MTX patients were evaluated for efficacy. Thirty-eight joints were counted. The number oftender and swollen joints, the Lansbury articular index, morning stiffness, activities of daily living (ADL) score, and erythrocyte sedimentation rate improved significantly in both groups without statistical intergroup differences. After 12 months, there was a significant deterioration of the mean Larsen index and the number of joints with erosions without intergroup difference. However, the radiological progression was retarded significantly during the second 6-month period in the gold group, whereas this effect was less pronounced in the MTX group. At 12 months, the progression rate was the same in both groups. PMID- 1749946 TI - Therapy for rheumatoid arthritis: combinations of disease-modifying drugs and new paradigms of treatment. AB - The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment. PMID- 1749947 TI - Pathogenesis of rheumatoid arthritis: basis for future therapies. AB - Despite an increase in the number of rheumatologists in clinical practice over the past 15 years, the outcome for patients with rheumatoid arthritis (RA) remains relatively poor. The poor prognosis for patients with this disease is due to a lack of effective therapies. Better therapies will be developed only after the cause and pathogenesis of RA are better understood. Although the precise cause is unknown, a variety of evidence indicates that RA results from the presentation of a relevant antigen to an immunogenetically susceptible host. This report reviews recognized potential antigens and known genetic variables affecting the immune response, as well as the various cellular and humoral immune responses that result from the antigen-host interaction. More successful therapy for RA will most certainly result from a better understanding of the pathobiology of the disease. PMID- 1749948 TI - Prognostic staging for therapy of rheumatoid arthritis. AB - An attempt should be made to predict the most likely course of individual disease when a patient is first diagnosed as having rheumatoid arthritis (RA). Such a prediction can be called prognostic staging for therapy. While no specific marker will accomplish this accurately, the summation of demographic, genetic, historical, physical, laboratory, radiologic, and scanning data may be used to make a reasonable estimation of outcome. The use of immunogenetic typing is the newest technique that can help identify patients likely to develop more serious disease. Once patients are identified as having probable aggressive disease, that is, beyond stage I, combination therapy should be initiated. Goals of therapy should include the prevention and/or interference of progression of radiologic erosions, as well as functional improvement as measured by life-style and productivity. PMID- 1749949 TI - [Organ donation. How to proceed with organ donation]. PMID- 1749950 TI - [Portuguese legislation on the utilization of organs and tissues]. PMID- 1749951 TI - [Joao Cidade, nurse of God]. PMID- 1749952 TI - [The psychotic patient]. PMID- 1749953 TI - [The role of nurses in promoting family life (the contribution of the Comitee International Catholique des Infirmieres et Assitantes Medico-Social for the WHO strategies for "Health for All in the Year 2000" and for the preparation and execution of the International Year of the Family in 1994)]. PMID- 1749954 TI - [A prayer from the sick person]. PMID- 1749955 TI - [The humanization of care. The paper crane]. PMID- 1749956 TI - [Ethical conflicts. The relation between parents and minor children and between guardians and the mentally retarded and the eventual conflict with the responsibility of the health team]. PMID- 1749957 TI - [The myths--and facts--about postoperative discomfit]. PMID- 1749958 TI - Demographic characteristics of cigarette smokers in the United States. AB - This research uses a multivariate log-linear examination of a national data set to analyze the combined influences of ethnicity, age, and sex on cigarette smoking status, not only for smokers but for former smokers and current nonsmokers as well. In general, we find that demographic differences in smoking vary across several dimensions. For instance, compared to females, males are more likely to smoke and to smoke heavily. The differences between male and female cessation rates vary with ethnicity; also, males and females tend to have different ratios of former smokers to light, moderate, and heavy smokers. Mexican Americans who smoke generally smoke small quantities of cigarettes. And Blacks are as likely as other groups not to smoke at all, and less likely than Anglos to smoke heavily. This article discusses potential future mortality effects, intervention strategies, and directions for future research. PMID- 1749959 TI - Seasonality of vital events in a Pacific Island population. AB - Analyses of vital data derived from a family record register for the native population of Guam reveal significant variations in births, deaths, and marriages over the period 1901-41. Although lacking marked photoperiod or temperature changes of temperate zones, the tropical island is subject to marked seasonal differences in rainfall characteristic of western Pacific islands. Marital patterns exhibit troughs associated respectively with the Lenten period and with Christmas celebrations. Infant and childhood deaths show close correspondence with rainfall patterns, consistently exceeding expected values during the rainy season (July-November) when conditions are optimal for the spread of communicable and gastrointestinal diseases. Births attain a peak in November, or at the beginning of the more advantageous season for infant health and survival. Seasonality in vital events, reported for many Euroamerican and some African and Asian populations of modern and historical periods, has rarely been documented for native populations of the tropical Pacific. Comparisons of differences in these patterns among different populations in varied environments provide unique opportunities to evaluate causal models of interactions among biological, sociocultural, and physioenvironmental factors. PMID- 1749960 TI - Effect of infertility on the population structure of the Herero and Mbanderu of southern Africa. AB - Analysis of the fertility of Herero and Mbanderu pastoralists of the northern Kalahari Desert of Botswana indicates that they have suffered from infertility. The smoothed population pyramid constructed from a recent census shows waves of births occurring about every 22 years. Since generation times in human populations are typically longer, we suggest that infertility is responsible for prematurely terminating the reproductive spans of women, resulting in a reduced generation time. The eigenvalues of a series of Leslie matrices indicate that the periods of oscillation in the population have increased from 22 to 29 years following the recovery from infertility. Increases in fertility since the 1950's have also transformed the Herero from a slowly declining population to one growing at a rate of nearly 3.5 per cent per year. PMID- 1749961 TI - Race of parents and infant birthweight in the United States. AB - Detailed 1977 national natality data are used to investigate social, demographic, and genetic effects on birthweight differentials. Analysis of birthweight differences among infants with white, black, and mixed black-white parents indicates that a portion of the observed weight differentials appear to be due to biologic factors. Infants with a black mother and father have the lowest mean birthweights, while infants with two white parents have the highest weights. Newborns with mixed-race parents have intermediate birthweight distributions. Multivariate analysis suggests that the effects of parental race on birthweight are not the result of maternal/obstetric differences among parents of the same or mixed race. PMID- 1749962 TI - Note on the reliability and validity of mothers' retrospective reports of their children's birthweights. AB - Using data from the 1973, 1976, and 1982 National Survey of Family Growth Studies, mothers' retrospective reports of their children's birthweights are compared across surveys and with vital registration data. Comparisons focus on estimated levels for blacks and whites, and on the effects of possible determinants. Despite the fact that nonresponse is more common for blacks, especially for births occurring at dates more distant from the surveys, results show that retrospective reports of low birthweight (less than 5.5 pounds) provide valid and reliable estimates of trends and differentials. PMID- 1749964 TI - Mean age and life expectancy at birth in stationary populations: comment. PMID- 1749963 TI - Births and cohort size. AB - Ahlburg (1983, 1986) tested a simple version of Easterlin's relative-cohort-size model of fertility on the basis of U.S. and Canadian post-war data. His conclusion was that the Easterlin model fits the data very well and can therefore be used for calculating forecasts. However, the model he estimated is oversimplified. In this paper an alternative specification is presented. The model is applied to Dutch fertility data. The Easterlin effect is found to affect the movement of births in the Netherlands during the period 1950-85, but a declining long-term trend in average family size proves far more important in explaining post-war births. The model forecasts a rise of births until 2000. PMID- 1749965 TI - Comment on "Sudden Infant Death Syndrome as a socially determined cause of death". PMID- 1749966 TI - Japanese migration in contemporary Japan: economic segmentation and interprefectural migration. AB - This paper examines the economic segmentation model in explaining 1985-86 Japanese interregional migration. The analysis takes advantage of statistical graphic techniques to illustrate the following substantive issues of interregional migration: (1) to examine whether economic segmentation significantly influences Japanese regional migration and (2) to explain socioeconomic characteristics of prefectures for both in- and out-migration. Analytic techniques include a latent structural equation (LISREL) methodology and statistical residual mapping. The residual dispersion patterns, for instance, suggest the extent to which socioeconomic and geopolitical variables explain migration differences by showing unique clusters of unexplained residuals. The analysis further points out that extraneous factors such as high residential land values, significant commuting populations, and regional-specific cultures and traditions need to be incorporated in the economic segmentation model in order to assess the extent of the model's reliability in explaining the pattern of interprefectural migration. PMID- 1749967 TI - Seasonality of births in human populations. AB - Seasonal fluctuations in births have been observed in virtually all human populations. In this paper we re-examine the seasonality of births with two main objectives in mind. The first is to provide an overview of the basic facts about the seasonality of births, presenting new estimates of the seasonal patterns. Seasonality is an important if not dominant source of nontrend variation in births in virtually all populations, but there are dramatic and puzzling differences across countries and time periods in the pattern of seasonal variation observed in particular populations. The second purpose of the paper is to survey the leading hypotheses about birth seasonality that have appeared in the literature and to discuss the consistency of these hypotheses with observed seasonal patterns. Using our estimates of seasonal patterns along with other evidence in the literature, we conclude that no single explanation receives strong, consistent support from the data. PMID- 1749968 TI - Voluntary childlessness among American men and women in the late 1980's. AB - Most studies of childlessness in the United States have relied on unrepresentative, opportunistic samples collected in a variety of ways. Thus, the relationship of various correlates to childlessness is not well known. Some studies have focused on demographic variables, but have not examined attitudinal factors associated with childlessness--something the opportunistic samples have been able to do. In this paper we examine both attitudinal and demographic factors associated with childlessness in the United States. The data used in this paper are from the National Survey of Families and Households collected in 1987 and 1988. The data set includes both demographic data, perceived advantages and disadvantages of having children, and attitudinal data about related social issues. Overall, the rate of voluntary childlessness was not high. Only 3.5 per cent of the men and 2.8 per cent of the women reported that they were childless and did not expect to have children. Only one category of people (unmarried men and women over the age of 35) had rates that exceeded ten per cent. A combined variable of age and marital status was the best predictor of childlessness. A scale of reasons or justifications for having children was the next best predictor. In addition, attendance at religious services, number of hours the respondents desired to work and education (for women only) were related to childlessness. Those who scored highly on measures of support for traditional families and support of extended families also tended to have lower rates of childlessness. Occupational status, religious denomination, and race, on the other hand, were not significantly related to childlessness. Measures of gender equality, religious fundamentalism, and support for mothers working were also not related to childlessness. PMID- 1749969 TI - Anticipated child loss to migration and sustained high fertility in an east Caribbean population. AB - Development today is commonly accompanied by rapid urbanization and, where possible, high rates of migration to industrialized countries. At the same time, the expected demographic transition has often not materialized despite decreases in death rates. Child-to-woman ratios in St. Vincent and the Grenadines are related to the educational attainment of women in a census district, the percentage of men engaged in agriculture, whether the district has direct access to the outside world through a port or airport, and, when the other variables are controlled, the stability of a district's population. Those districts with the greatest stability of population had the lowest child-to-woman ratios, suggesting that the anticipated loss of children to migration may be an important factor in maintaining high reproductive rates. PMID- 1749970 TI - Chaplains and the health care team. PMID- 1749971 TI - What to say to persons with HIV disease. AB - I believe that the circumstances in which one learns of being infected with human immunodeficiency virus (HIV) can form a pattern that may either hasten or postpone the physical and psychologic progress of HIV to full-blown AIDS. The experience of learning about one's seropositivity from one's physician sets the stage for the patient to determine who else needs to be told. This paper discusses the steps in communicating the diagnosis of seropositivity. PMID- 1749972 TI - Endovascular infections caused by enterococci highly resistant to ampicillin. AB - Enterococci frequently cause endocarditis and are the most common gram-positive isolates in polymicrobial bacteremia. We report three cases of polymicrobial endovascular infections at a single institution during a 12-month period; the enterococcal isolates were highly resistant to penicillins. These cases comprised 18% of all enterococcal endovascular isolates during the same 12-month period. Previous use of antibiotics, presence of endovascular catheters, and nosocomial acquisition of the organism occurred in all three cases. Clinicians should be aware of enterococcal resistance to penicillins and should exercise care in designing appropriate regimens for serious enterococcal infections. PMID- 1749973 TI - Emphysematous pyelitis and emphysematous pyelonephritis characterized by computerized tomography. AB - We report three cases of emphysematous pyelonephritis, all of them associated with perinephric emphysema, and one case of emphysematous pyelitis to demonstrate the value of computerized tomography (CT) in both diagnosis and patient management. The differentiation between air in the collecting system (emphysematous pyelitis), air within the parenchyma (emphysematous pyelonephritis), and air in the perinephric space (perinephric emphysema) may have significant prognostic (survival) and therapeutic (medical vs surgical) implications. Computerized tomography is currently the best method for demonstrating intrarenal air and for characterizing the location of that air (intracalyceal, intraparenchymal, perinephric, or pararenal). PMID- 1749974 TI - Cutaneous aging: effect of intrinsic changes on surgical considerations. AB - Intrinsic age-related structural and functional changes in the skin, independent of sun-induced damage, directly affect wound healing in the elderly. These alterations, as well as concomitant medical illness, pharmaceutical intake, and dietary changes, result in delayed wound healing, decreased ultimate tensile strength, and increased rates of wound dehiscence, ecchymosis, tape-strip injuries, infection, and persistent contact dermatitis. PMID- 1749975 TI - Evaluation of surgical services in a large university-affiliated VA hospital: use of an in-house-generated quality assurance data base. AB - In this era of occurrence screening, increased documentation of surgical resident supervision, and overall efforts to alter quality of patient care through increased documentation, an in-house quality assurance data base can greatly facilitate these activities. To establish a data base, 6241 operative procedures over a 15-month interval were logged into a StatView II Database using the patient's name and record number, diagnosis, and operative information available from the standard operation report worksheet. Additional information, including the name of the supervising staff and level of supervision, had also been recorded concurrently on this form. Each month, after this demographic information has been entered into the data base for each surgical service, it is reviewed, ensuring 100% surveillance of all cases. The subsequent morbidity and mortality (M & M) information is then added to the data base. Using the contingency table option of the StatView II Database, quarterly and annual reviews have been done to study individual services, types of cases, staff attending, individual supervision, levels of staff involvement, and incidence of complications. Our Surgical Service has reported an overall morbidity of 306 cases (4.9%) and mortality of 71 (1.14%). Average numerically coded levels of resident supervision have been compiled with regard to individual services and staff surgeons. This data base has proved helpful in the recredentialling process of our surgical staff, resident logs, identification of necessary reviews of certain case types, and formation of a computerized operative log. PMID- 1749976 TI - Flow cytometry of needle aspirates from bone and soft tissue tumors. AB - Fine needle aspiration specimens from 29 patients with bone and soft tissue neoplasms were analyzed by flow cytometry for DNA index and cell cycle analysis to determine whether such studies were helpful in cytologic diagnosis. Of 15 cases initially cytologically diagnosed as benign, 14 had a DNA index of 1.0, indicating a diploid population. The remaining case diagnosed as cytologically benign had a DNA index of 1.3. Further tissue from this tumor revealed an osteogenic sarcoma. Of the 14 cases initially diagnosed as malignant, 12 were hyperdiploid. Cell cycle analysis showed that malignant tumors had a higher proportion of cells in S phase (15.2% +/- 8.7%) than benign tumors (6.9% +/- 1.6%). Furthermore, high-grade malignancies had a significantly greater number of cells in S phase (18.5% +/- 1.5%) than low-grade tumors (9.9% +/- 6.3%). PMID- 1749977 TI - Awareness of substance abuse in orthopedic patients: a survey of orthopedic surgeons. AB - We surveyed 178 orthopedic physicians in the Washington, DC, area to ascertain the effect on patient care of previous education in the area of drug and alcohol issues. The return rate was 75%. Of the respondents, 99% were male, average age was 46.7 years (+/- 9.3), and average number of years in practice was 15.2 (+/- 9.6). A majority of respondents indicated that they did not have training in the abuse potential of analgesics (92 [69%]), characteristics of benzodiazepine abuse (77 [58%]), or when to seek the assistance of an addiction medicine specialist for patients with chronic pain (106 [80%]). Only 41 (31%) of the orthopedists indicated that they inquire about alcohol and drug use before prescribing opiates for more than a week. We offer suggestions for self-education for interested physicians. PMID- 1749978 TI - Analgesia after thoracotomy in children: a comparison of interpleural, epidural, and intravenous analgesia. AB - The cohort for this study included 39 patients, between the ages of 8 and 20 years, who had had thoracotomy. Postoperative analgesia was provided by one of three techniques: intravenous narcotics (20 patients), thoracic epidural catheter (10 patients), or interpleural analgesia (IPA) (nine patients). Both IPA and epidural analgesia were administered according to a specific protocol. The efficacy of the three methods was evaluated using two indicators: the total intravenous narcotic requirements for the initial 72 hours and the number of times a dose of intravenous narcotic or supplemental epidural fentanyl was administered to each patient. Patients in the IPA group required significantly less intravenous narcotics (P less than .05) during the first three postoperative days (2.2 +/- 0.4, 1.9 +/- 0.6, and 1.4 +/- 0.5 mg of meperidine/kg/day) than patients in the intravenous narcotic group (8.1 +/- 1.2, 7.2 +/- 0.9, and 5.6 +/- 1.2 mg of meperidine/kg/day). When comparing epidural analgesia and IPA, the number of interventions in the patients receiving epidural analgesia was significantly less (P less than .05) than in the group receiving IPA. Four of 10 patients in the epidural group and two of nine in the IPA group required no interventions during the initial 72-hour postoperative course. In the epidural analgesia group, there were 19 days (of a total of 30 days) during which patients required no interventions. This percentage was significantly greater (P less than .05) than that of the IPA group, in which there were 9 days (of a total of 27 days), during which no interventions were required. PMID- 1749979 TI - Inpatient cardiopulmonary resuscitation: is survival prediction possible? AB - We retrospectively reviewed 443 patients who had cardiopulmonary resuscitation (CPR). The focus of the study was to discover what preexisting factors should be assessed to determine the probability of survival. There were 88 successes out of 340 cases (25.9%). The absence of a previous myocardial infarction (MI), shock, partial pressure of oxygen (PaO2) less than 60 mm Hg, blood urea nitrogen (BUN) level greater than 20 mg/dL, pneumonia, pulmonary edema, and oliguria were found to predict a successful outcome. Logistic regression was used to predict percentage of successes in the various groups of patients with various clinical characteristics. The observed and predicted numbers of successes were in close agreement in most cases. We also constructed a classification function to predict whether an individual subject would survive the event for which CPR was required. Sixty-seven of the 88 observed successes would have been predicted, for an estimated sensitivity of 76%, and 164 of the 252 failures would have been predicted, for an estimated specificity of 65%. A large percentage (24%) of cases in which the patient actually survived CPR would have been predicted to be failures. We conclude that preexisting factors before a cardiopulmonary arrest do not accurately predict survival after CPR. PMID- 1749980 TI - Ectopic pregnancy in an urban teaching hospital: can tubal rupture be predicted? AB - We evaluated the medical history, physical examination, and laboratory tests done on 245 patients with laparoscopically proven ectopic pregnancies. The absence of abdominal pain was the only clinically useful negative predictive value (91%) regarding tubal rupture. Although mean levels of serum human chorionic gonadotropin (hCG-beta subunit) were significantly higher in patients with ruptured versus unruptured ectopic pregnancies (16,612 mIU/mL vs 6406 mIU/mL), no breakpoint excluded the possibility of tubal rupture. In fact, one third of ectopic pregnancies in patients with a serum beta-hCG level below 100 mIU/mL were ruptured. We conclude that clinical symptoms and signs are poor predictors of tubal rupture. In addition, absolute values of serum beta-hCG are not helpful in excluding the possibility of rupture. PMID- 1749981 TI - Diet, behavior modification, and exercise: a review of obesity treatments from a long-term perspective. AB - Reviewed herein are the long-term weight loss outcomes of three fairly recent major modifications of standard dietary therapy for obesity. Appraised separately and in combination, these therapeutic approaches are very low calorie diets (VLCD), behavior modification, and exercise. The weight loss results from VLCD are impressive for only the first 6 to 10 months. Adding behavioral procedures to VLCD increases the weight loss for the first year or two, but not in 3 to 5 years. Adding exercise further increases the weight loss at 1 to 2 years, and those who continue regular exercise achieve the best weight loss results 1 to 6 years later. PMID- 1749982 TI - Myths about vitamin B12 deficiency. AB - Neurologic manifestations of vitamin B12 deficiency are protean, including neuropathy, depression, and dementia. We present evidence to dispel confounding myths about vitamin B12 deficiency. Hematologic indices are normal in up to 30% of patients with vitamin B12 deficiency, and results of the Schilling test may be normal in patients with symptoms of deficiency. Isolated neuropathy or myelopathy may occur independently, but often appear concurrently. The neuropathy is primarily axonal and predominantly sensory. Myelopathy is caused by demyelinated areas in posterior and lateral columns. After therapy, recovery from neuropathy is incomplete or may extend for several years. Vitamin B12 replacement should not be withheld from patients with borderline vitamin B12 levels, since the consequences of allowing myelopathy, neuropathy, dementia, and mental disorders to worsen clearly outweigh any disadvantage of therapy. PMID- 1749983 TI - Use of the chaplaincy in the neonatal intensive care unit. AB - The hospital chaplain is a relatively new member of the health care team, and there is little objective information on the chaplaincy's role in the hospital. To evaluate the chaplain's role, I collected information from the chaplain's daily logs and from a medical staff/parent questionnaire on the use of the chaplaincy in the neonatal intensive care unit (NICU). Both the medical/nursing staff and the chaplains viewed the chaplain's role as encompassing both traditional (religious functionary) and nontraditional functions. However, the medical/nursing staff consulted chaplains only for traditional roles. The discrepancy in chaplain use suggests a need for objective study about the chaplain's role. I offer hypotheses for testing the role of the chaplaincy in the NICU. PMID- 1749984 TI - Horace Smithy: pioneer heart surgeon. PMID- 1749985 TI - William Harvey and the circulation of the blood. PMID- 1749986 TI - Plato's cavagram: shadows on the wall of the reading room. PMID- 1749987 TI - Incisional hernias: factors influencing development. AB - We have presented a study of 125 patients treated for incisional hernia. This complication occurred more frequently in women (81%), and gynecologic and obstetric procedures were responsible for 58%. The method of surgical repair in all cases was peritoneal-aponeurotic transposition. The 5-year recurrence rate was less than 3%. PMID- 1749989 TI - Comparing ECGs. PMID- 1749988 TI - Mycobacterium kansasii infection in a patient with AIDS. AB - We have presented the case of a 45-year-old HIV-positive man who had a 2-week history of shortness of breath and fever and who was found to have pneumonia due to an acid-fast bacillus. Despite treatment with isoniazid, rifampin, ethambutol, and clofazimine, he died of the infection. Culture results obtained after his death showed the organism to be Mycobacterium kansasii. Mycobacterial infections are common in patients with AIDS, but are usually due to M tuberculosis or M avium complex. Of the 35 patients with AIDS and M kansasii infection mentioned in the literature, only eight of these were described; and of the four patients (including our patient) who received therapy considered appropriate for this infection, only two survived. PMID- 1749991 TI - Hodgkin's disease in epitrochlear lymph node only. PMID- 1749990 TI - Imipramine-induced syndrome of inappropriate antidiuretic hormone secretion. PMID- 1749992 TI - Aspartame. PMID- 1749993 TI - Hyperpyrexia as the sole symptom of thyrotoxicosis. PMID- 1749994 TI - Periactin for headache. PMID- 1749995 TI - Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leukocyte antigen haplotype. AB - To evaluate the genetic background of ossification of the posterior longitudinal ligament, the relationship between the presence of absence of ossification and human leukocyte antigen haplotypes was studied in 33 families of patients with ossification of the posterior longitudinal ligament. The study revealed that human leukocyte antigen haplotypes formed certain types of clusters, and that some human leukocyte antigen haplotypes were very rare in the Japanese population, suggesting the involvement of human leukocyte antigen-linked factors in the pathogenesis of ossification of the posterior longitudinal ligament of the cervical spine. In the families of these patients, ossification of the posterior longitudinal ligament was demonstrated by radiography in 56% (10/18) of the siblings. Each of these siblings shared both human leukocyte antigen haplotypes with the patient. None of those who shared only one human leukocyte antigen haplotype with the patient had developed ossification of the posterior longitudinal ligament. From these findings, the presence of both pathogenic human leukocyte antigen haplotypes is considered to be necessary for the development of ossification of the posterior longitudinal ligament, and this genetic predisposition may be activated by multiple factors, including regressive degeneration due to aging and the environment. PMID- 1749996 TI - Comparative study between magnetic resonance imaging and histopathologic findings in ossification or calcification of ligaments. AB - Magnetic resonance imaging findings were compared with histopathologic specimens of ossified or calcified ligaments, including the surrounding tissue, to evaluate the usefulness of magnetic resonance imaging as a means to predict the progression of ossification. In addition, factors influencing signal intensity were evaluated by histochemical and immunohistochemical analyses. The area of low signal intensity corresponded to the hyperplastic ligament around the ossification, and to the transitional area between the ligament and the ossification. A mineralization front and chondrocyte proliferation with strong metachromasia were recognized in these areas. The presence of a low-intensity signal area suggested the progression of ossification. The isointensity signal corresponded to proliferation of small vessels in the hyperplastic ligament, presumably representing the initiation of ossification. Histochemically, the metachromasia was intense at the transitional area between the ligament and the ossification, and the main constituent in these areas was chondroitin sulfate. Immunohistochemically, S-100 protein, transforming growth factor-beta 1, and Type II collagen showed an intense immunoreactivity in the chondrocytes, indicating increased production of the extracellular matrix. We postulate that the activation of chondrocytes and the alteration of the extracellular matrix may have affected the signal intensity. PMID- 1749997 TI - Magnetic resonance imaging and histologic study of hypertrophic cervical posterior longitudinal ligament. A case report. AB - Magnetic resonance imaging and histologic features of hypertrophic cervical posterior longitudinal ligament were determined in a cervical myelopathy patient. On T1-weighted images, the thickened ligament and the prolapsed nucleus pulposus showed isointensity shadows, making it impossible to differentiate these tissues. On T2-weighted images, the thickened ligament and prolapsed nucleus pulposus were visualized at high and low intensity, respectively. Sagittal T1-weighted images after gadolinium-diethylene triamine pentaacetic acid injection showed obvious enhancement of the thickened ligament. PMID- 1749998 TI - A simple technique for cervical myelography. AB - A new method has been devised for obtaining high-quality cervical myelograms safely and easily through lumbar injection. This method uses simple radiographic equipment, and does not require a tiltable table or fluoroscopy. Fifty-seven patients with cervical disorders were examined by this method using 9.5 ml of iohexol (300 mg l/ml), and successful myelograms were obtained in all patients. No serious complications were encountered. PMID- 1749999 TI - Bilateral open laminoplasty using ceramic laminas for cervical myelopathy. AB - Evaluation was done of 65 patients with cervical myelopathy treated by bilateral open laminoplasty using artificial laminas, between 1984 and 1988, who had been followed for more than 2 years. The mean recovery rate on the Japanese Orthopaedic Association scoring system was 65% in all cases, and 72% in the cases with no other complications. The artificial laminas appeared well adapted to the laminas in computed tomography and dynamic radiographic examinations, and there were no cases of reduction of the enlarged canal. Postoperative restriction of the range of motion of the cervical spine was lessened by the positioning of lateral grooves, more appropriate external fixation, and posterior flexion exercise after operation. This procedure is not technically complicated, it does not involve appreciable blood loss during operation, it prevents grafted free fat from migrating into the spinal canal, and is advantageous for posterolateral bone chip grafting. PMID- 1750000 TI - Neurologic complications of surgery for cervical compression myelopathy. AB - Neurologic complications resulting from surgery for 384 cases of cervical myelopathy (cervical soft disc herniation, spondylosis, ossification of the posterior longitudinal ligament) were reviewed. Surgical procedures performed included 134 anterior interbody fusions (Cloward or Robinson-Smith technique), 70 subtotal corpectomies with strut bone graft, 85 laminectomies, and 95 laminoplasties. Twenty-one patients (5.5%) sustained neurologic deterioration related to surgery. The deterioration was classified into two types on the basis of the neurologic signs observed: deterioration of spinal cord function or of nerve root function. Manifestations of the former varied from weakness of the hand to tetraparesis. Paralysis of the deltoid and biceps brachii muscles was an exclusive feature of deterioration in the nerve root group. Causes of this paralysis included malalignment of the spine related to graft complications, and a tethering effect on the nerve root following major shifting of the spinal cord after decompression. The causes of deterioration of the cord function included spinal cord injury during surgery, malalignment of the spine associated with graft complication, and epidural hematoma. PMID- 1750001 TI - Changes in the evoked spinal cord potentials associated with chronic experimental cord compression. AB - To determine the functional changes occurring in the early period after the development of chronic cord compression, an ossification of the ligamentum flavum model, which is a model of chronic cord compression, was created in domestic rabbits using bone morphogenetic protein, and monitored evoked spinal cord potentials. Sixty-seven rabbits were used for these experiments. Myelography, evoked spinal cord potential measurements, and histologic examinations were performed in 16 of the ossification of the ligamentum flavum rabbits and six of the healthy control rabbits. Our results show that 1) mild degrees of cord compression produce greater evoked spinal cord potential alterations in chronic than in acute compression, as reported in the literature; 2) chronic compression from the dorsal side produces injury in the superficial layer of the dorsal column and dorsolateral column; and 3) changes in evoked spinal cord potentials precede the development of paralysis and histologic changes. PMID- 1750002 TI - Intraoperative monitoring for tethered spinal cord syndrome. AB - Functions of the lower extremities and bowel and bladder must be monitored during releasing surgery for tethered spinal cord syndrome, because neural elements are embedded in lipoma or anomalous tissues. Evoked muscle action potentials of the external anal sphincter muscle, external urethral sphincter muscle, and lower extremity muscles can indicate promptly whether or not neural elements are involved before the surgeon releases or cuts the tissue for cord release. It is also important to monitor vesical pressure because of different types of innervation from the external urethral and anal sphincters, in spite of slow reaction times of vesical pressure elevation. Evoked muscle action potentials indicate only motor function; therefore, it is more appropriate to record evoked spinal cord potentials from the spinal cord above a lumbosacral operative field, because sensory function can also be monitored. Evoked muscle action potentials are an easy and extremely sensitive monitoring system; nevertheless, monitoring of vesical pressure and evoked spinal cord potentials should also be done to achieve optimum monitoring. For the past 5 years, 10 patients have undergone cord release surgery with such a monitoring system, and the results indicate no exacerbating case. PMID- 1750003 TI - Spinal dysraphism. A study of patients over the age of 10 years. AB - Thirty patients over the age of 10 years, exhibiting cutaneous manifestations on the back suspected to be due to spinal dysraphism, and neurologic deficits, were studied to analyze neurologic appearance. Neurologic deficits appeared by age 5 in 26 patients. No patient complained of low-back pain or sciatica. Paralytic deformities of the lower extremities were divided into four grades for evaluation: A = no deformity, with only urinary disturbance (four cases); B = toe limited deformity (two cases); C = toe and foot-limited deformity (six cases); D = toe, foot, ankle, and lower limb deformity (18 cases). Patients with slight neurologic disturbance, either Grade A or without urinary disturbance, were seen among the patients who had undergone a release operation by age 2, although neurologic appearance in patients in severe grades was not related to the age at release operation. Also, the release operation was thought to be effective in preventing low-back pain or sciatica. PMID- 1750004 TI - Cotrel-Dubousset pedicle screw system for various spinal disorders. Merits and problems. AB - Eighty-five consecutive patients with various spinal disorders who underwent surgery using the Cotrel-Dubousset pedicle screw system at Kantoh Rosai Hospital between August 1986 and November 1989 were studied. The group included 52 men and 33 women, ranging in age from 19 to 76 years, with an average age of 53 years. The postoperative follow-up period was from 15 to 54 months, with an average of 33 months. The diagnoses were lumbar degenerative disorders in 69 cases (spondylolisthesis in 32, lumbar degenerative spinal canal stenosis without spondylolisthesis in 21, and "unstable lumbar spine" in 16), spinal trauma in 9, spinal deformities in 5 (scoliosis in 3 and kyphosis in 2), and tumor in 2 (1 spinal cord tumor and 1 vertebral tumor). The Cotrel-Dubousset pedicle screw system proved not only to be useful in fixing an unstable spine from the lower thoracic vertebra to the sacrum, as is the case with the other pedicle screw systems, but also to have great advantages for use in various spinal disorders, including reduction of slipped vertebra, correction of spinal deformity combined with a hook system, and for anterior spinal instrumentation. Postoperative clinical results were good in most of the cases, but pseudarthrosis considerably affected the results in a few cases. Therefore, great care must be taken, both strategically and technically, to prevent pseudarthrosis. PMID- 1750005 TI - A biomechanical analysis of Zielke, Kaneda, and Cotrel-Dubousset instrumentations in thoracolumbar scoliosis. A calf spine model. AB - A biomechanical study was performed in order to evaluate the initial stability of three spinal instrumentation systems, applied to a scoliosis model. Five calf spines (T11-L2) were destabilized anteriorly, and, by inserting a wedge-shaped resin disc within each destabilized intervertebral space, a thoracolumbar scoliosis was created. Three spinal instrumentation systems (Zielke anterior instrumentation, Kaneda anterior multisegmental fixation device, and Cotrel Dubousset posterior instrumentation) were applied to correct the simulated scoliotic condition. Mechanical nondestructive cyclical testing in axial compression, rotation, flexion, and extension was performed on each spinal construct. The Kaneda device was the most stable instrumentation in all four loading conditions. Zielke instrumentation failed to restore the stability to the level of the intact spine in rotation, and was the least rigid instrumentation in flexion and extension. The Cotrel-Dubousset instrumentation demonstrated favorable stability in flexion and extension, but became the least rigid instrumentation in axial compression and rotation. This study suggests that a one stage procedure with Zielke instrumentation and a two-stage procedure (anterior release with bone graft and posterior stabilization) with Cotrel-Dubousset instrumentation applied for the correction of scoliosis, should be supplemented with additional external or internal supports. The Kaneda device may offer enough stability with an anterior procedure alone in the correction of scoliosis. PMID- 1750006 TI - Diagnosis and operative treatment of intraforaminal and extraforaminal nerve root compression. AB - The clinical, radiologic, and operative findings, and clinical results in 26 cases of foraminal nerve root involvement, each treated by variable operative procedures for an existing pathologic condition, were studied. These 26 cases consisted of 8 intraforaminal or extraforaminal lumbar disc herniations and 18 foraminal nerve root entrapments. The cases with an extreme lateral lumbar disc herniation underwent lateral fenestration or osteoplastic hemilaminectomy without concomitant spinal fusion, and showed excellent operative results. A sufficient selective decompression was achieved with a good clinical result in the cases of lumbar spondylosis without preoperative spinal instability, by lateral fenestration or osteoplastic hemilaminectomy. This result suggests that the selective decompression procedure is recommended for cases with reliable preoperative diagnoses. When an intraspinal lesion makes it difficult to diagnose coexisting foraminal nerve root involvement, decompression of the nerve root canal, approaching from medial to lateral, is recommended. The fusion operation should be performed in cases undergoing even a unilateral total facetectomy, regardless of the patient's old age. A correct preoperative diagnosis is crucial in order to obtain satisfactory operative results. PMID- 1750007 TI - A quantitative evaluation of sensory dysfunction in lumbosacral radiculopathy. AB - A quantitative evaluation of sensory disturbance of the foot was attempted in 94 cases of lumbosacral radiculopathy using the biothesiometer, the Semmes-Weinstein esthesiometer, light touch, tuning fork, and dermatomal somatosensory evoked potentials. Dermatomal somatosensory evoked potentials was the most sensitive of these tests, and reflected the duration of the lumbosacral radiculopathy better than the biothesiometer and the Semmes-Weinstein esthesiometer. The biothesiometer and Semmes-Weinstein esthesiometer reflected the clinical severity of sensory dysfunctions, the extent of numbness, and the immediate change in sensory function better than the dermatomal somatosensory evoked potentials. It is important to understand the characteristics of each test and to choose informative tests for clinical use. Grades of sensory disturbance in patients with lumbosacral radiculopathy were classified into three categories in combination with the findings of dermatomal somatosensory evoked potentials and the values recorded with the biothesiometer and Semmes-Weinstein esthesiometer. PMID- 1750008 TI - The Steffee variable screw placement system using different methods of bone grafting. AB - Two groups of patients with diseased lumbar spines treated by the Steffee variable screw placement system were studied, in order to compare concomitant posterolateral fusion and posterior lumbar interbody fusion. The use of posterolateral fusion resulted in less invasiveness than posterior lumbar interbody fusion, with regard to operating time and blood loss. With the posterolateral fusion method, correction of olisthesis or kyphotic deformity, if attained at all, was difficult to maintain. Posterior lumbar interbody fusion produced better correction and maintenance, even in osteoporotic cases. Bone union was achieved at an average of 11 months in only 60% of the posterolateral fusion group, whereas it was complete within a significantly shorter period (average; 6 months) in 91% of the posterior lumbar interbody fusion group. Breakage or loosening of screws occurred in 14% of the posterolateral fusion group. Deep wound infection and adhesive arachnoiditis, which were never seen in the posterolateral fusion group, developed in 3% of the posterior lumbar interbody fusion group. Posterior lumbar interbody fusion is considered to be a better method of bone grafting than posterolateral fusion, when used with the Steffee variable screw placement system. PMID- 1750009 TI - An experimental study on transpedicular screw fixation in relation to osteoporosis of the lumbar spine. AB - In order to elucidate the relationship between the severity of osteoporosis and the fixation strength of a pedicle screw, screw pull-out tests were performed using cadaveric lumbar vertebrae. The severity of osteoporosis was evaluated by the Jikei osteoporosis grading scale (Jikei method), bone mineral density, and microdensitometry. When a 7.0-mm screw was used, the pull-out force of the screw was 1,056.4 N in the normal group (as determined by the Jikei method), while it was 495.6 N in the Grade I osteoporosis and 269.5 N in the Grade II osteoporosis groups, respectively. There were also positive correlations between the pull-out force and bone mineral density and each parameter of the microdensitometry method. When bone cement was used in an osteoporotic vertebra, twofold stronger pull-out force was obtained in comparison to that obtained without bone cement. PMID- 1750010 TI - Cervical myelopathy with Prader-Willi syndrome in a 13-year-old boy. A case report. PMID- 1750011 TI - Spinal metastasis of sweat gland carcinoma. A case report. PMID- 1750012 TI - Conjoined nerve roots associated with lumbosacral spine anomalies. A case report. PMID- 1750013 TI - Tuberculosis in the Third World. PMID- 1750014 TI - Extracorporeal membrane oxygenation: a breath of fresh air or yesterday's treatment? PMID- 1750015 TI - Body composition and exercise performance in patients with chronic obstructive pulmonary disease. AB - To investigate whether a compromised nutritional state may limit exercise performance in patients with chronic obstructive pulmonary disease we studied 54 such patients (FEV1 less than 50% and arterial oxygen tension (PaO2) greater than 7.3 kPa) whose clinical condition was stable and who were admitted to a pulmonary rehabilitation centre. Fat free mass was assessed anthropometrically (from skinfold measurements at four sites) and by bioelectrical impedance; creatinine height index and arm muscle circumference were also assessed. The mean (SD) distance walked in 12 minutes was 845 (178) m. No association was established between the distance walked and spirometric measures. A good correlation was found between the distance walked and fat free mass in the whole group (r = 0.73 for impedance measurements and 0.65 for skinfold thickness) and in a subgroup of 23 lean patients (body weight less than 90% of ideal weight; r = 0.66 for impedance measurements and 0.46 for skinfold thickness). Body weight correlated with the distance walked only in the whole group (r = 0.61). On stepwise regression analysis fat free mass measured by bioelectrical impedance, maximal inspiratory mouth pressure, and PaO2 accounted for 60% of the variation in the distance walked in 12 minutes. We conclude that fat free mass, independently of airflow obstruction, is an important determinant of exercise performance in patients with severe chronic obstructive pulmonary disease. PMID- 1750016 TI - Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease. AB - BACKGROUND As respiratory virus infections often lead to exacerbations of chronic bronchitis and asthma an effective antiviral drug may be helpful in such patients. Alpha 2 interferon has been shown to give protection against rhinovirus infections in field studies. METHODS Patients with chronic respiratory disease exposed to close contacts with symptoms of upper respiratory tract infection were randomly allocated to receive nasal sprays of recombinant alpha 2 interferon (3 x 10(6) IU) or placebo twice daily for five days. Of the 123 patients recruited into the study, 69 took 117 courses of medication; 11 courses were excluded from analysis. RESULTS No important side effects were recorded and the incidence of possible adverse effects was similar in the two groups. Interferon treatment did not reduce the number or severity of symptomatic episodes; 11 of 48 patients given interferon and 16 of 58 given placebo developed lower respiratory symptoms. There were no differences in mean symptom scores (51 interferon and 52 placebo), number of symptomatic days (3.3 interferon and 5.0 placebo), peak flow values, number of general practitioner consultations, or use of antibiotics. CONCLUSION Alpha 2 interferon 3 x 10(6) IU taken twice daily for five days does not protect patients with chronic respiratory disease from exacerbations after they have been in contact with an upper respiratory tract infection. PMID- 1750017 TI - Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. AB - BACKGROUND The metered dose inhaler is difficult to use correctly, synchronising actuation with inhalation being the most important problem. A breath actuated pressurised inhaler, designed to help patients with poor inhaler technique, was compared with a conventional metered dose inhaler in terms of aerosol deposition and bronchodilator response. METHODS Radioaerosol deposition and bronchodilator response to 100 micrograms salbutamol were measured in 18 asthmatic patients, who inhaled from a conventional metered dose inhaler by their own chosen metered dose inhaler technique, from a conventional metered dose inhaler by a taught metered dose inhaler technique, and from a breath actuated pressured inhaler (Autohaler). RESULTS In the 10 patients who could coordinate actuation and inhalation of the inhaler on their own deposition of aerosol in the lungs and bronchodilator response were equivalent on the three study days. By contrast, in the eight patients who could not coordinate the mean (SEM) percentage of the dose deposited in the lungs with their own inhaler technique (7.2% (3.4%] was substantial lower than those attained by the taught metered dose inhaler technique (22.8% (2.5%] and by Autohaler (20.8% (1.7%]. CONCLUSION Although of little additional benefit to asthmatic patients with good coordination, the Autohaler is potentially a valuable aid to those with poor coordination, and should be considered in preference to a conventional metered dose inhaler in any patient whose inhaler technique is not known to be satisfactory. PMID- 1750018 TI - Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers. AB - BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials. PMID- 1750019 TI - Diagnostic value of lung clearance of 99mTc DTPA compared with other non-invasive investigations in Pneumocystis carinii pneumonia in AIDS. AB - Various non-invasive investigations were carried out in patients infected with HIV who had respiratory symptoms with and without pneumocystis pneumonia (with pneumonia, n = 13 (five smokers); without pneumonia, n = 22 (13 smokers]. These included chest radiography; lung function tests (forced expiratory volume in one second, forced vital capacity; transfer factor and coefficient for carbon monoxide); arterial blood gas tensions; arterial oxygen saturation at rest and on exercise; and lung clearance of diethylenetriaminepenta-acetic acid labelled with technetium-99m (99mTc DTPA). The effect of scan time (seven v 45 minutes from peak counts) and subtraction of background counts were examined. There were no significant differences between the two groups in lung function tests or arterial blood gas tensions at rest. The median clearance half time of inhaled 99mTc DTPA for the first seven minutes from peak counts was 7.2 minutes for patients with pneumocystis pneumonia and 22 minutes for those without. The median arterial oxygen desaturation on exercise was 5% in patients with pneumocystis pneumonia and 2% in those without. 99mTc DTPA lung clearance was better than the other non invasive tests in discriminating pneumocystis pneumonia from other pulmonary disorders in patients positive for HIV. A short scan time of seven minutes was as sensitive and specific as the longer scan time of 45 minutes, and this allows the clearance of 99mTc DTPA to become a rapid screening test. PMID- 1750020 TI - Results of thoracotomy in osteogenic sarcoma with pulmonary metastases. AB - BACKGROUND Resection of pulmonary metastases may be followed by long term survival and now that it is an accepted method of treatment for patients with osteogenic sarcoma indicators of favourable prognosis are needed to aid the assessment of suitability for resection. This study compares the survival rates of patients who did and did not undergo resection of their pulmonary metastases and relates them to prognostic indicators. METHODS The study population was the 43 patients with osteosarcoma who developed pulmonary metastases out of the 111 patients with osteosarcoma treated by the Birmingham bone tumour treatment service during 1977-83. All patients who developed metastases confined to the lungs were considered for resection, thoracotomy being advised for all patients (provided that they were fit enough) who had metastases thought to be resectable even if they were multiple. RESULTS Of the 18 patients who did not have a thoracotomy, 15 died of disseminated disease after a mean interval of eight months; one patient died of cardiomyopathy and two are alive after 26 and eight months. Of the 25 patients who underwent thoracotomy in an attempt to resect metastases, three were found to have inoperable disease and died after a mean interval of 5.4 months from thoracotomy. Overall, after thoracotomy (repeated if necessary) there was a 20% survival at five years from the first thoracotomy. When survival was assessed with respect to the disease free interval and the number and bilaterality of the metastases no significant relationships were found. There was, however, a significant relation between survival and the position of metastases, patients with metastases confined to one lobe of the lung having a mean survival of 29.5 months, compared with 13.7 months in patients with disease in more than one lobe. CONCLUSION Thus patients who had a thoracotomy survived longer from the time of diagnosis of pulmonary metastasis than those not undergoing thoracotomy; metastases confined to one lobe predicted a better prognosis. PMID- 1750021 TI - Measurement of tracheobronchial clearance after sauna in subjects with chronic bronchitis. AB - The effect of sauna on tracheobronchial clearance was studied in five male patients with chronic bronchitis by a radioaerosol technique. No enhancement of tracheobronchial clearance could be detected. PMID- 1750022 TI - What makes granulomas tick? PMID- 1750023 TI - Mycobacterium fortuitum lung abscess treated with ciprofloxacin. AB - Mycobacterium fortuitum rarely causes lung disease. Although treatment in the past has included intravenous antibiotics, this is the first report of a Mycobacterium fortuitum lung abscess that resolved with a prolonged course of oral ciprofloxacin alone. There is no evidence of recurrence 14 months after the end of treatment. PMID- 1750024 TI - Computed tomography and magnetic resonance findings in lipoid pneumonia. AB - A case of exogenous lipoid pneumonia was documented by computed tomography and magnetic resonance imaging. Although strongly suggesting the presence of fat on T1 weighted images, magnetic resonance does not produce images specific for this condition. Computed tomography is the best imaging modality for its diagnosis. PMID- 1750025 TI - Percutaneous biopsy of mediastinal tumours under sonographic guidance. PMID- 1750026 TI - The laryngeal mask airway and flexible bronchoscopy. PMID- 1750027 TI - [A non-specific veterinarian]. AB - John Akkermans, who became 65 on july 4th, 1991, started his veterinary career on december 1st, 1952. He contributed in many ways to veterinary science. In the Netherlands many diseases were diagnosed by him for the first time. He had the ability to arouse the interest of many for his findings by writing papers as the sole author. But by stimulating his co-workers even more papers were published of which he was co-author and not always the first one. He was obviously able to follow the developments in veterinary science and animal husbandry without any problems and to create openings when the profession was confronted by problems. He was often involved in diseases of pigs but also in furred animals and ruminants. He was not a specialist in a single species of animal or in a single professional area, but in several fields. Not a specialist, but a more specific veterinarian in the sense that he is unique. PMID- 1750028 TI - [Changed health problems in a changing pig-farming concern in The Netherlands until 1980]. AB - In 1905 Poels published 'Disease of swine in the Netherlands'. This book dealt predominantly with swine fever, erysipelas, tuberculosis and 'pneumonia'. Between 1920 and 1940 others reported on streptococci, lobular haemmorrhagic pneumonia, bordetellosis, Aujeszky's disease and postweaning diarrhoea. After the second world war, particularly after 1960, the Dutch pig-farming industry developed at a tremendous rate. As a consequence, the health problems changed. Certain diseases became less important: tuberculosis, erysipelas, Leptospira tarrasovi, enteroviruses. Yet other diseases including postweaning diarrhoea, atrophic rhinitis and Aujeszky's disease became problems of increasing importance. At the end of the seventies the knowledge of E. coli toxin types was substantial. On the other hand, information concerning the pathogenesis and pathophysiology was very limited. Bordetella bronchiseptica was still considered to be the most important agent in AR, zootechnical factors being predisposing. However, one was aware of missing links. Aujeszky's disease was obscure until the late fifties. Until 1972 only occasional reports were made. In that year, an epidemic occurred in the Gelderse Vallei. Another epidemic occurred in 1974 in the provinces of Brabant and Limburg. By 1980 proper vaccines were available and Aujeszky's disease was not yet a political problem. PMID- 1750029 TI - [The Veterinary Service Board, EEC-guidelines for the protection of the welfare of domestic animals]. PMID- 1750030 TI - [Atrophic rhinitis A.D. 1991]. AB - In the Netherlands the Central Veterinary Institute (CVI) and the Animal Health Services carried out investigations on aetiology, pathogenesis, therapy and prevention of Atrophic Rhinitis (AR) since 1970. Since the discovery of AR toxin in AR pathogenic P. multocida in SPF piglets, quicker and cheaper tests were developed e.g. the mouse test and guinea pig skin test. Today ELISA-tests with poly- and monoclonals are also available. The CVI carried out DNA probes and is developing a PCR-test. Tests to detect a natural infection were difficult to develop. The SN test by Bechmann, the skin test by Schimmelpfenning and the ELISA test by Foged give some perspectives. From investigations with B. bronchiseptica in piglets, it appears that the role of this germ is overestimated in the development of AR. On 16-week-old pigs an infection with AR toxigenic P. multocida caused conchae atrophy and septum deviation within 4 weeks. This fact has to be taken into account concerning the preventive medications in piglets. Only high maternal antibody titres against the AR toxin are able to protect the piglets for a sufficiently long period. Conchae atrophy and brachygnathia superior are indicators for suspicion of AR but do not prove the diagnosis of AR. By means of selective agars the isolation of P. multocida from nose, tonsils and lungs could be improved. The incubation period of clinical AR may last longer than two years. The AR pathogenic P. multocida is predominantly transmitted by pigs, incidentally also by rabbits, cattle, sheep, goat, poultry, dogs and cats. Humans can get infected and diseased. The AR pathogenic P. multocida has to be classified as a zoonosis. By way of stamping out and air filtering the transmission can be prevented. Vaccination cannot avoid an infection with the AR pathogenic P. multocida. The Animal Health Services developed a program to certify breeding herds 'free of AR pathogenic P. multocida'. PMID- 1750031 TI - [Towards a better health status in pig farming]. AB - The Dutch pig-farming industry is on the verge of sweeping changes due to national and European legislation and changes towards a buyers market. An improved health-status is a necessity. Such improvements must fall in line with changes in the industry. This paper presents the characteristics of primary, secondary and tertiary infectious disease, and methods by which improvements can be achieved. These are: stamping out; systematic vaccinations; systematic pre medications; improved husbandry; in-line production; breeding for improved disease-resistance; the SPF system; and Early Medicated Weaning. In the Dutch pig farming industry the number of farms will decrease to approx. 10,000. These farms will be organised in vertically integrated production systems. IN CONCLUSION: improvement of the national pig-health status is acquired through vertically integrated production systems under improved husbandry conditions. Particular infectious microorganisms will be banned through EEC regulations; other diseases will be minimised by vaccination. Selection for disease-resistance will contribute to some extent to an improved health-status in the future. PMID- 1750032 TI - [Coprophagia in dogs]. PMID- 1750033 TI - [A belly full of lucky breaks]. PMID- 1750034 TI - [The Veterinary Service Board. Legislation for the practice of veterinary medicine]. PMID- 1750035 TI - Regional blood flow in skeletal muscle measured by the heated thermocouple method during electrical nerve stimulation of the canine gracilis muscle. AB - Skeletal muscle blood flow (MBF) and intramuscular pressure (IMP) were measured using a heated thermocouple (HTC) and a solid-state catheter-tip transducer during electrical nerve stimulation in the gracilis muscle of anesthetized dogs. MBF values obtained simultaneously by the HTC method and the inhalated hydrogen gas (H2) clearance method showed an excellent linear regression with a correlation coefficient of 0.93. Electrical nerve stimulation at frequencies of 5 and 100 Hz increased total MBF, determined by an electromagnetic flowmeter, over control values 6.57 +/- 0.82 and 6.32 +/- 0.93 ml/min/100 g, respectively. Regional MBF at 5 Hz stimulation determined with HTC increased in the same magnitude both at the midpoint and the distal portion of the gracilis muscle. However, following 100 Hz stimulation, MBF at the midpoint was decreased from 8.15 +/- 1.55 to 4.09 +/- 1.54 ml/min/100 g, whereas at the distal portion flow was increased from 6.39 +/- 1.71 to 21.2 +/- 5.29 ml/min/100 g. IMP in both regions was low and approximately 2.0 mmHg at rest. IMP was remarkably increased to 27.9 +/- 8.43 mmHg at the midpoint but not in the distal portion during 100 Hz tetanic contraction, but showed no significant change in either region following 5 Hz stimulation. These data suggest that HTC can serve to measure MBF, and that following 100 Hz tetanic contraction, increased IMP may be associated with decreased regional MBF, irrespective of a total increase in flow in the gracilis muscle. PMID- 1750036 TI - Effects of elastic loading and exercise on pulmonary gas exchange in dogs. AB - We assessed the effects of negative intrathoracic pressure induced by inspiratory elastic loading on pulmonary, gas exchange with and without electrically induced hindlimb exercise in 8 normal, anesthetized dogs. Two elastic loads (EL) were used; one of 81 and one of 140 cmH2O/liter. These are equivalent to doubling and tripling the normal elastance of the dog's respiratory system, respectively. Elastic loading decreased ventilation and caused hypoxemia and hypercapnia, but it did not affect systemic arterial pressure or heart rate. During exercise, increase in ventilation was limited, whereas increase in cardiac output was not affected by elastic loading. Alveolar-arterial O2 tension difference (A-aDO2) was not changed significantly by exercise alone. However, elastic loading accompanied by exercise increased A-aDO2. Although comparable end-inspiratory pleural pressure was achieved with large EL (-29 +/- 2 cmH2O, mean +/- SE) and small EL with exercise (-30 +/- 2 cmH2O), the latter increased A-aDO2 whereas the former did not. Large negative intrapleural pressure combined with increased cardiac output may have caused transient interstitial edema. PMID- 1750037 TI - Establishment of an estrogen receptor-positive cell line (HMA-1) derived from human breast carcinoma. AB - We have established a novel human breast carcinoma cell line, HMA-1, derived from ascites of a female breast cancer patient. HMA-1 was shown to be an epithelial cell line with intracytoplasmic duct-like vacuoles, microvilli, desmosomes and tonofibrils in accordance with human breast cancer. The cell line demonstrated a good cell growth ability in monolayer fashion with a doubling time of 46 hr. Based on a whole cell binding assay the cell line contained estrogen receptor (1.45 x 10(-4) sites/cell). Tamoxifen, an anti-estrogen agent induced a dose dependent decrease in the cell growth rate, but estradiol stimulated the cell growth. HMA-1 could be transplanted subcutaneously into BALB/c nude mice, and was able to cause tumors approximately two months after heteroinoculation. These results indicate that HMA-1 cell line may serve as a new human breast carcinoma cell line which could be utilized in the breast cancer research. PMID- 1750038 TI - Association between renal tubular dysfunction and mortality among residents in a cadmium-polluted area, Nagasaki, Japan. AB - A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex- and age- specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary beta 2-microglobulin (beta 2-m) concentration greater than 1,000 microgram/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary beta 2-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary beta 2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality. PMID- 1750039 TI - Environmental pollutants and diseases. A cell biological approach using chronic cadmium exposure in the animal model as a paradigm case. PMID- 1750040 TI - A critical appraisal of stroke evaluation and rating scales. AB - BACKGROUND: To judge the efficacy of new, putative stroke therapies, we need a method to measure neurological deficit accurately in groups of patients before and after treatment. No single measurement technique has yet proven to be universally acceptable, but one approach is the use of rating instruments that summarize the neurological deficit found on clinical examination. Currently, stroke assessment scales may be based on the examination of physical deficits, an inventory of activities of daily living, or a global evaluation of functional outcome. SUMMARY OF REVIEW: Scientific methods for authenticating stroke scales are available in the psychometric and statistical literature. We review currently available stroke scales for their validity and reliability and propose investigations needed to refine further the standardized measurement of neurological deficit following stroke. CONCLUSIONS: We suggest that clinical stroke trials include a physical deficit scale and a global rating during the acute phase and that an activities of daily living scale be added at later points in recovery. PMID- 1750041 TI - Selection process for surgeons in the Asymptomatic Carotid Atherosclerosis Study. AB - BACKGROUND AND PURPOSE: The Asymptomatic Carotid Atherosclerosis Study is a prospective, multicenter, randomized clinical trial of carotid endarterectomy for the treatment of asymptomatic hemodynamically significant stenosis. This report describes the selection process for participating surgeons in the trial. METHODS: The Surgical Management Committee established guidelines for minimal annual experience and maximum neurological morbidity and mortality for surgeons to qualify to participate in the study. For approval, a surgeon must perform at least 12 carotid endarterectomies per year. Based on a review of the surgeon's last 50 consecutive endarterectomies, the combined neurological morbidity and mortality rate must be no greater than 5% for all indications and no greater than 3% for endarterectomies performed on asymptomatic patients. RESULTS: One hundred sixty-four surgeons from 48 centers applied for approval: 117 were approved, 17 were rejected, and 30 were not reviewed. The 117 approved surgeons submitted a total of 5,641 endarterectomies with a combined mortality and neurological morbidity rate of 2.3% for the variety of indications for operation. CONCLUSIONS: This overall experience with carotid endarterectomy is one of the largest series reported to date. The data from approved surgeons are well within the range of acceptable neurological morbidity and mortality rates recommended by the Stroke Council of the American Heart Association, which attests to the overall quality of the surgeons participating in the study. PMID- 1750042 TI - Systemic vascular changes in spontaneous occlusion of the circle of Willis. AB - BACKGROUND AND PURPOSE: We examined the presence of systemic etiologic factors causing vascular changes in so-called "spontaneous occlusion of the circle of Willis" (cerebrovascular moyamoya disease) to determine whether extracranial, as well as intracranial, vessels are involved in this disease. METHODS: Histopathologic examination and morphometric analysis of the extracranial vessels were performed in 13 patients with this disease. RESULTS: The histopathologic findings of the extracranial vessels were as follows: 1) advanced intimal fibrous thickening similar to that of the intracranial vessels; and 2) characteristic intimal fibrous nodular thickening, which may indicate organization of mural thrombi, at the proximal portions of the pulmonary arteries in three of 13 patients. Morphometric analysis revealed significant intimal thickening of the pulmonary arteries (p less than 0.05), renal arteries (p less than 0.05), and pancreatic arteries (p less than 0.01) in patients with this disease as compared with age- and sex-matched control patients. CONCLUSIONS: On the basis of these findings, it is highly likely that this disease has systemic etiologic factors, as well as focal etiologic factors, that work to create vascular change in both the intracranial and extracranial vessels. PMID- 1750043 TI - Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats. AB - BACKGROUND AND PURPOSE: The aim of the study was to selectively examine the effects of converting enzyme inhibition on the large brain arteries by using concomitant inhibition of carbonic anhydrase to cause severe dilatation of mainly parenchymal resistance vessels. METHODS: Cerebral blood flow was measured using the xenon-133 injection technique in three groups of Wistar rats either during carbonic anhydrase inhibition with acetazolamide (treatment A, n = 8), during carbonic anhydrase inhibition followed by converting enzyme inhibition with captopril 40 minutes later (treatment B, n = 10), or during carbonic anhydrase inhibition preceded by converting enzyme inhibition 20 minutes earlier (treatment C, n = 7). RESULTS: After treatment A, cerebral blood flow rose rapidly and stabilized within 20 minutes at an average of 220 ml/100 g.min; flow remained stable until at least 60 minutes. After treatment B, cerebral blood flow increased by a further 17.4%, from an average of 219 ml/100 g.min to an average of 257 ml/100 g.min (p less than 0.01). After treatment C, cerebral blood flow stabilized at an average of 238 ml/100 g.min, with flow from 20 to 60 minutes always being higher (from 5% to 17%) than during carbonic anhydrase inhibition alone (p less than 0.02). Thus the additional inhibition of converting enzyme resulted in higher cerebral blood flow than during inhibition of carbonic anhydrase alone. CONCLUSIONS: These results suggest that converting enzyme inhibition reduced resistance of large brain arteries and support the hypothesis that there is some angiotensin II-induced tone in large cerebral arteries. PMID- 1750044 TI - Lacunar infarcts. Pathogenesis and validity of the clinical syndromes. AB - BACKGROUND AND PURPOSE: In this study, we investigated the lacunar hypothesis to answer three questions: 1) Is the lacunar syndrome valid for diagnosing lacunar infarction? 2) What is the frequency of potential cardiac versus carotid sources of embolism in patients with lacunar versus cortical infarct? 3) What is the frequency of vascular risk factors in these two groups of patients? METHODS: The study was performed in a well-defined prospective series of 103 patients with a first-ever lacunar infarct and 144 other patients with a first-ever infarct involving the cortex. RESULTS: Sensitivity and specificity of the lacunar syndromes in diagnosing lacunar infarction were 95% and 93%, respectively. Positive and negative predictive values of diagnosing lacunar infarction in patients with lacunar syndromes were 90% and 97%, respectively. Risk factor analysis showed no differences for either group of cerebral infarction. A cardiac source of embolism was significantly less frequent in patients with lacunar infarction (odds ratio = 0.32, 95% confidence interval = 0.17-0.61, p less than 0.001). Significant carotid stenosis (diameter reduction greater than or equal to 50%) was also less frequent in patients with lacunar infarction (odds ratio = 0.35, 95% confidence interval = 0.16-0.76, p less than 0.001). CONCLUSIONS: These findings show that the lacunar syndrome is an excellent clinical test for diagnosing lacunar infarction and that cardiac and carotid embolism are unlikely causes of lacunar infarction, supporting the hypothesis that lacunar infarcts are usually caused by small vessel disease. PMID- 1750045 TI - Incidence of silent lacunar lesion in normal adults and its relation to cerebral blood flow and risk factors. AB - BACKGROUND AND PURPOSE: There are few reports comparing incidence of silent lacunar lesions detected by magnetic resonance imaging and cerebral blood flow in neurologically normal adults. METHODS: We studied the incidence of such lesions and its relation to cerebral blood flow and risk factors in 246 neurologically normal adults (145 men, mean age 62 years; 101 women, mean age 60 years) who received health screening examinations of the brain. RESULTS: Thirty-two subjects (13%) had possible silent lacunar lesions (66% of these were recognized by both T1- and T2-weighted image). The regional cerebral blood flow measured by the xenon-133 inhalation method was significantly lower in subjects with silent lacunes than in those without (p less than 0.02). Cerebral blood flow was mildly but significantly decreased in those with silent lacunes (p less than 0.05). Periventricular hyperintensity was closely related to silent lacune (p less than 0.01). However, there was no significant difference in cerebral blood flow between subjects with and without apparent periventricular hyperintensity. CONCLUSIONS: Silent lacunar lesion was closely related to decrease of cerebral circulation and may be an important risk factor for symptomatic cerebrovascular disease. PMID- 1750046 TI - Cerebral blood flow and neuropsychological asymmetries in unilateral stroke. AB - BACKGROUND AND PURPOSE: This study sought to determine the degree of agreement between asymmetries of neuropsychological functioning and nine methods of quantifying asymmetries of regional cerebral blood flow. METHODS: The regional cerebral blood flow methods combined three markers of cerebral blood flow asymmetry (percent hemispheric difference, maximum percent probe-pair asymmetry, and number of probe-pair asymmetries) with three indexes of regional cerebral blood flow (fast compartment flow, initial slope index, and initial slope). Eleven patients with left hemispheric ischemic strokes and 13 with right hemispheric ischemic strokes were studied with the xenon-133 inhalation technique and neuropsychological tests. RESULTS: Blind clinical judgments of neuropsychological asymmetry significantly correlated with all nine methods of cerebral blood flow asymmetry determination; correlations ranged from -0.42 to 0.77. Clinical judgment of asymmetry of neuropsychological functioning accurately predicted the hemisphere of lower flow in 71-92% of cases, depending on the method of cerebral blood flow asymmetry determination. Agreement between cerebral blood flow and neurobehavioral signs of asymmetry was greater for initial slope and initial slope index than for the fast flow index. The initial slope and initial slope index showed equally good agreement. The use of the number of asymmetrical probe pairs to detect cerebral blood flow asymmetries agreed less well with neurobehavioral asymmetry than did the other two markers studied. CONCLUSIONS: Both the initial slope index and the initial slope measures of cerebral blood flow are useful in predicting neuropsychological asymmetries, especially when the magnitude of the asymmetry is taken into account. PMID- 1750047 TI - 14,15-Epoxyeicosatrienoic acid inhibits platelet aggregation in mouse cerebral arterioles. AB - BACKGROUND AND PURPOSE: Epoxygenase metabolites of arachidonic acid are produced by several tissues and have been shown to inhibit in vitro platelet aggregation. The purpose of the present investigation was to determine whether 14,15- or 8,9 epoxyeicosatrienoic acid, epoxygenase derivatives of arachidonic acid, affect the speed of platelet aggregation in in vivo mouse cerebral arterioles. METHODS: We performed a craniectomy in 116 anesthetized male mice and observed the pial arterioles by microscopy. We induced in situ platelet aggregation using a mercury light and intravascularly injected fluorescein dye. RESULTS: Indomethacin (0.5 mg/kg i.p.), a known cyclooxygenase inhibitor, and 14,15-epoxyeicosatrienoic acid (0.3 mg/kg i.v.) increased the time necessary for the light plus dye to induce the first arterial platelet aggregate by 35% and 26%, respectively, whereas 8,9 epoxyeicosatrienoic acid (0.3 mg/kg i.v.) had no effect. Analysis of mouse serum by radioimmunoassay showed that the degree of inhibition of platelet aggregation by indomethacin and epoxyeicosatrienoic acids correlated with the degree of inhibition of thromboxane production. CONCLUSIONS: We conclude that 14,15 epoxyeicosatrienoic acid is a potent inhibitor of in vivo platelet aggregation but cannot conclusively confirm that its effect on aggregation occurs via its reduction of platelet thromboxane A2. Because epoxyeicosatrienoic acids are produced by several tissues, including brain and vascular tissue, they may be important in vivo modulators of platelet aggregation and hemostasis. PMID- 1750048 TI - Dietary treatment of atherosclerosis abolishes hyperresponsiveness of retinal blood vessels to serotonin in monkeys. AB - BACKGROUND AND PURPOSE: Atherosclerosis alters vascular responses of the eye to serotonin. Augmented vasoconstrictor responses in the retina to serotonin are associated with functional impairment and may contribute to amaurosis fugax. The goal of this study was to test the hypothesis that dietary treatment of atherosclerosis restores vascular responses of the eye toward normal. METHODS: We measured blood flow to the retina using microspheres in six normal monkeys, five atherosclerotic monkeys, and five atherosclerotic monkeys that were fed a normal (regression) diet for 18 months. RESULTS: Infusion of 8 and 40 micrograms.min 1.kg-1 serotonin into the left atrium had little effect on blood flow to the retina in normal monkeys. In contrast, the high dose of serotonin reduced blood flow to the retina by a mean +/- SEM of 81 +/- 9% (p less than 0.05) in atherosclerotic monkeys. In monkeys that were fed the regression diet, serotonin had no effect on blood flow to the retina. CONCLUSIONS: Regression of atherosclerosis abolishes augmented responses of the retinal circulation to serotonin. PMID- 1750049 TI - Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery. AB - BACKGROUND AND PURPOSE: Experiments were carried out in rabbits to determine whether clentiazem (8-chlorodiltiazem), a cerebrovascular-selective calcium channel blocker, administered 24 hours before subarachnoid hemorrhage influenced the subsequent cerebral vasospasm. METHODS: Subarachnoid hemorrhage was induced by multiple injections of blood into the prepontine cisterns of 35 male New Zealand White rabbits, and clentiazem (5 mg/kg) was administered 4 times daily until sacrifice. Cerebral artery diameter was assessed in vivo by angiography. Functional features of basilar arteries were measured using conventional in vitro methodology. RESULTS: Clentiazem reduced the angiographic narrowing seen on days 2 and 5 from 35% and 34%, respectively (sham control, 1.42 +/- 0.31 mm [n = 22]), to 8% and 11%, respectively, and prevented the narrowing (32%) that occurred on day 9. Narrowing in the untreated rabbits was only partly reversed by papaverine; all narrowing in clentiazem-treated animals was papaverine sensitive. Clentiazem prevented or reduced many of the changes in the basilar artery caused by the subarachnoid hemorrhage. Of particular relevance to arterial narrowing were the increased wall stiffness, the transient spontaneous changes in wall force, and the reduction in relaxation to acetylcholine. Reduction of the changes in wall force induced by agonists and by stimulation of intramural sympathetic nerves was observed. CONCLUSIONS: The vascular damage associated with chronic cerebral vasospasm is related to calcium entry into the smooth muscle and endothelial cells, and possibly sympathetic nerve terminals, through calcium channels sensitive to clentiazem, which suggests that clentiazem may be of value in the management of chronic cerebral vasospasm. PMID- 1750050 TI - Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats. AB - BACKGROUND AND PURPOSE: We sought to determine the effects of aging on regional cerebral blood flow and ischemic brain damage in transient cerebral ischemia in rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of bilateral carotid occlusion and 60 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Regional cerebral blood flow in the hippocampus and striatum was measured using the hydrogen clearance method. Nine adult and 14 aged rats were subjected to 20 minutes of bilateral carotid occlusion or were sham-operated under ether anesthesia. Seven days after 20 minutes of cerebral ischemia, the rats' brains were perfusion fixed. Ischemic damage in the hippocampus and striatum was graded (0 [normal] to 3 [majority of neurons damaged]). RESULTS: After 20 minutes of bilateral carotid occlusion, striatal cerebral blood flow decreased to 9.1 +/- 1.5 and 3.9 +/- 2.0 ml/100 g/min in aged and adult rats, respectively, and hippocampal cerebral blood flow decreased to 8.6 +/- 2.4 and 5.7 +/- 2.4 in aged and adult rats, respectively. Although these ischemic cerebral blood flow values were not significantly different between the two age groups, scores for ischemic damage in the hippocampus CA-1 subfield and striatum were significantly higher in aged than in adult rats (p less than 0.05, Kruskal-Wallis' h test with Bonferroni correction). CONCLUSIONS: We conclude that aging may be a primary factor in the development of greater ischemic neuronal damage observed in aged hypertensive rats. PMID- 1750051 TI - Does vasospasm occur in small pial arteries and arterioles of rabbits? AB - BACKGROUND: Vasospasm is a serious complication associated with subarachnoid hemorrhage. Successful management of vasospasm will ultimately depend on a clear understanding of the scope of this phenomenon, including whether arterial elements of different calibers are equally affected. We therefore examined the responses to subarachnoid hemorrhage in rabbit basilar arteries, small pial arteries, and arterioles. SUMMARY OF REPORT: We compared the brain stem pial arteries of 10 perfusion-fixed male New Zealand White rabbits after experimental subarachnoid hemorrhage to those of five control rabbits using morphological analysis of cross-sections of plastic-embedded vessels. After subarachnoid hemorrhage, the internal elastic lamina was highly corrugated in all basilar arteries (mean diameter 319 +/- 51 microns). These arteries were severely constricted in comparison with the control group, in which the mean diameter was 691 +/- 17 microns, and corrugation of the internal elastic lamina was not present. In contrast, small pial arteries and arterioles very rarely demonstrated a vasoconstrictive configuration after subarachnoid hemorrhage. The contractility of the smaller vessels was confirmed by injecting 2 mg/kg BaCl2 intracisternally. Following BaCl2 injection, corrugation of the internal elastic lamina was detected in the small arteries and arterioles as well as the basilar arteries. CONCLUSIONS: We conclude that experimental chronic vasospasm after subarachnoid hemorrhage in rabbits tends to occur in large conducting arteries rather than in smaller pial arteries and arterioles. PMID- 1750052 TI - Familial association of intracranial aneurysms and cervical artery dissections. AB - BACKGROUND AND PURPOSE: The familial occurrence of intracranial aneurysms and cervical artery dissections has been described in different families and supports the hypothesis that a primary arteriopathy may play a role in the pathogenesis of these disorders. Although the basis for this arteriopathy is generally not believed to be similar among cases of intracranial aneurysms and cervical artery dissections, several similarities exist in the epidemiology of these disorders and a common underlying arterial abnormality may be suspected. SUMMARY OF REPORTS: The medical records of all 175 patients with spontaneous dissections of the cervical arteries who were seen at the Mayo Clinic between 1970 and 1989 were reviewed to identify families in which intracranial aneurysms and cervical dissections coexisted. Three families were identified in which intracranial aneurysms and cervical artery dissections were observed among siblings. These families are described in detail. CONCLUSIONS: The familial occurrence of intracranial aneurysms and cervical artery dissections within the same families provides support to the importance of a common underlying arteriopathy in the pathogenesis of both these disorders. The underlying vascular defect may, at least in some cases, be inherited. PMID- 1750053 TI - Deriving clinical prediction rules from stroke outcome research. AB - BACKGROUND AND PURPOSE: Our purpose was to determine whether clinical prediction rules could be derived from current stroke outcome research. SUMMARY OF REPORT: We reviewed 92 articles on stroke outcome research to determine their suitability for implementation as a clinical prediction rule. Methodological problems in many of these studies made implementation of their results as a clinical prediction rule difficult. CONCLUSIONS: Implementation of stroke outcome research as clinical prediction rules would be facilitated by description of patient population demographics; precise definitions of predictor and outcome measures; stratification of patients by stroke mechanism; use of adequate patient sample sizes; and description of the mathematical methods used, including coding schemes, cutpoints, beta coefficients, constant terms, and a priori probabilities. PMID- 1750054 TI - Cerebral vasculitis associated with cocaine abuse. AB - BACKGROUND: Earlier reports of cocaine-associated cerebral vasculitis have been based primarily on angiographic findings without pathological verification. CASE DESCRIPTION: We present a case of acute encephalopathy following intravenous and intranasal administration of cocaine. Brain biopsy revealed vascular changes involving primarily small arteries. Findings included lymphocytic infiltration, endothelial thickening, and deposition of proteinaceous amorphous material within and around vessel walls. CONCLUSIONS: These abnormalities are consistent with pathological features of arteritis previously reported in association with amphetamine and multiple-drug abuse. Vasospasm-induced changes are an alternative explanation for the vascular picture seen in this case. The patient made modest improvement with high-dose intravenous steroids. PMID- 1750055 TI - Lacunar infarctions due to cholesterol emboli. AB - BACKGROUND AND PURPOSE: Hypertension is commonly considered the major cause of lacunar infarctions. However, in some cases, it has been suggested that lacunes could be caused by cerebral emboli from cardiac or carotid sources. Cholesterol cerebral emboli have been rarely reported as a cause of lacunes. CASE DESCRIPTION: We describe a 79-year-old patient with a progressive multi-infarct dementia who developed transient motor aphasia and paresis of the right arm. Computed tomography showed lacunar infarcts in the right caudate nucleus, left thalamus, and left putamen, as well as an old right frontal infarction. Neuropathological examination demonstrated no prominent vascular hyalinosis, but did show multiple cholesterol emboli occluding small arteries around lacunar infarcts and leptomeningeal arteries near cortical infarcts. The cholesterol material presumably originated in the extended atheromatous changes along the aortic arch. CONCLUSIONS: Our report confirms that lacunes can be caused by cholesterol emboli in some patients. Small cerebral emboli should not be overlooked as a cause of lacunes. PMID- 1750056 TI - Evidence of somatotopic organization of the sensory thalamus based on infarction in the nucleus ventralis posterior. AB - BACKGROUND: This is to describe a restricted sensory syndrome of unique distribution due to thalamic infarct. CASE DESCRIPTION: We report a case of pure sensory disturbance involving the left intraoral and perioral regions and the tips of the thumb and forefinger of the left hand. Magnetic resonance imaging revealed a small infarct in the contralateral thalamus, presumably affecting the nucleus ventralis posterior. CONCLUSIONS: This patient provides an excellent correlation between clinical findings and thalamic representation of body surface as established during stereotactic procedures. PMID- 1750057 TI - Central nervous system complications of infective endocarditis. PMID- 1750058 TI - South Australian stroke rehabilitation outcome study. PMID- 1750059 TI - Responses of rat basilar artery to acetylcholine and platelet products in vivo. PMID- 1750060 TI - Effect of elevated norepinephrine levels on electrocardiographic changes in subarachnoid hemorrhage. PMID- 1750061 TI - Improvement in experimental cardiac preservation based on metabolic considerations. AB - Viability of rat hearts preserved in the standard Euro-Collins and a modified preservation medium utilizing the Euro-Collins medium as the base were assessed. The additions for the modified medium were chosen in order to attenuate the various forms of damage that may occur to an organ during cold ischemia. The viability of the hearts was assessed biochemically via 31P nuclear magnetic resonance spectroscopy and functionally during reperfusion in an isolated Langendorff preparation. It was noted that a modified medium containing magnesium, adenosine, allopurinol, glutathione, and polyethylene glycol provided superior protection of the cold ischemic myocardium as compared with the standard Euro-Collins medium in the isolated heart perfusion apparatus. Both physiologic function (dp/dt) and metabolic status (Pi/PCr ratio) were superior with the modified compared with the control medium (325 +/- 83 vs. 90 +/- 35 mmHg/sec and 0.42 +/- .09 vs. 0.68 +/- .05, respectively, both P less than 0.05). Moreover, this modified solution resulted in more rapid development of contractions, as well as improved Pi/PCr ratio (0.71 +/- .32 vs. 2.02 +/- .59, P less than 0.05) in the in vivo heterotopic transplant model. It seems likely that a combination of pharmacologic additives may be developed that synergistically attenuate damage to the preserved myocardium. PMID- 1750062 TI - The quality of initial function following renal transplantation determined by creatinine elimination kinetics. Comparison of Minnesota antilymphocyte globulin and cyclosporine induction immunosuppression. AB - To compare the effect of type of induction immunosuppression on the quality of initial renal allograft function, we identified 35 cadaver donor kidney pairs in which one recipient of a kidney from a given pair received induction immunosuppression with Minnesota antilymphocyte globulin (MALG group) while the recipient of the contra-lateral kidney received cyclosporine from day zero (CsA group). In the absence of an existing quantitative measure to assess and compare the status of those grafts that function primarily, we defined the half-life of creatinine elimination (t1/2SCr) as such an outcome measure based on a review of creatinine elimination kinetics. All organs were procured with in-situ perfusion and en-bloc removal. Total cold storage times, rewarm times, and perioperative management were comparable for the two groups. In the MALG group, the mean t1/2SCr) was not different from that in the CsA group (1.38 +/- 0.96 days vs 1.35 +/- 1.2 days P = NS). Multiple regression analysis performed on the differences in recipient age, number of DR-B locus matches, total cold ischemia time, rewarm time, and central venous pressure at reperfusion of a given donor pair demonstrated no significant impact of any of these differences on the difference in t1/2SCr for the same pair set in this sample. The nadir of serum creatinine achieved in the first five days posttransplant was somewhat higher in the CsA group (234 +/- 131 mumol/L) as compared with the MALG group (200 +/- 132 mumol/L) but the difference was not significant. A similar nonsignificant trend was observed in the comparison of mean serum creatinine values at 30 days posttransplant (MALG group: 158 +/- 62 mumol/L vs. CsA group: 200 +/- 141 mumol/L). Only one of seventy recipients (CsA group) was dialyzed within the first 5 days posttransplant for an overall incidence of ATN of less than 2%. Fourteen of 35 (40%) recipients in both groups received treatment for acute rejection. The mean time to first treatment for acute rejection episode was shorter in the CsA group than the MALG group (10 +/- 8 days vs 23 +/- 24 days, P = 0.055). Graft survival at one year was not different for the two groups (92% vs. 87% for the MALG and CsA groups respectively, P = NS).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1750063 TI - Hepatic dysfunction following T-cell-depleted allogeneic bone marrow transplantation. AB - We reviewed the medical records of 97 patients undergoing T cell-depleted allogeneic bone marrow transplantation at our institution from 1984 to 1990 to determine the incidence of hepatic dysfunction, including venoocclusive disease of the liver following BMT. All patients received allogeneic marrow that had been purged with monoclonal antibody to the CD6 surface antigen (T12) and rabbit complement as the sole method of graft-versus-host disease prophylaxis. No additional immunosuppressive agents were routinely administered to these patients. Overall, 55% of patients in our series developed two-fold elevations in serum bilirubin, SGOT, or alkaline phosphatase within the first 30 days following BMT. A five-fold elevation in any liver function test was noted in only 19% of patients. Logistic regression analysis revealed that the presence of GVHD, female sex, and administration of amphotericin B all were independently associated with laboratory evidence of hepatic dysfunction. While LFT abnormalities were common in our series, they were generally mild, and the development of VOD was rare. Only three patients (3.1%) fulfilled clinical criteria sufficient to establish a diagnosis of VOD. Among the 86 patients whose ablative regimen consisted of cyclophosphamide (60 mg/kg x2) and total-body irradiation (1200-1400 cGy in 200 cGy fractions), only 1 patient (1.2%) developed VOD. Our experience suggests that patients undergoing allogeneic BMT are at low risk for VOD and other serious hepatic complications when they receive high-dose cyclophosphamide, fractionated TBI, and T cell-depleted marrow without hepatotoxic medications for GVHD prophylaxis. PMID- 1750064 TI - Biliary secretion of bile acids, lipids, and bilirubin by the transplanted liver. A quantitative study in patients on cyclosporine. AB - To investigate biliary secretion in liver-transplanted patients on cyclosporine treatment we used duodenal perfusion with a nonabsorbable marker. After an overnight fast, 4 women and 5 men were studied for 6 hr at least 6 weeks after orthotopic liver transplantation. The data were compared with those obtained in 6 healthy controls. All transplanted patients received immunosuppressive therapy (corticosteroids, azathioprine, and cyclosporine). Biliary secretion rates of healthy controls were: bile acids 1.58 +/- 0.67 mmol/hr, phospholipids 0.27 +/- 0.11 mmol/hr, cholesterol 0.11 +/- 0.01 mmol/hr, and bilirubin 18 +/- 0.7 mumol/hr (mean +/- SEM). Liver-transplanted patients excreted 2.60 +/- 0.4 mmol/hr bile acids, 0.56 +/- 0.08 mmol/hr phospholipids, 0.18 +/- 0.04 mmol/hr cholesterol, and 22.0 +/- 4.5 mumol/hr bilirubin. Analysis of individual bile acids revealed that in the bile of liver transplant patients the percentage of cholic acid was elevated, whereas that of deoxycholic acid was reduced as compared with controls. These findings indicate that in the transplanted liver under immunosuppressive therapy with cyclosporine biliary secretion of bile acids, lipids, and bilirubin is not reduced. PMID- 1750065 TI - bcr/abl mRNA detection following bone marrow transplantation for chronic myelogenous leukemia. AB - We have utilized the polymerase chain reaction (PCR) to sensitively detect persistence of the chronic myelogenous leukemia (CML) malignant clone and to study bcr/abl mRNA splicing patterns following bone marrow transplantation. Thirteen of sixteen patients displayed persistent malignant cells during post-BMT clinical remission. In two patients bcr/abl mRNA was detected 4 and 9 months prior to clinical relapse. In eleven of fourteen patients in continued clinical remission malignant cells were detected post-BMT. Ten of these eleven patients were also cytogenetically normal. Seven patients have lost all evidence of bcr/abl transcript, but only at 1-2 years posttransplant, while four have shown persistence of the bcr/abl transcript from 28 days to 3 years post-BMT and one has converted from an initially negative result at 1 year post-BMT to detectable levels of chimeric mRNA at 2 years. Thus, 8/9 patients tested at or before 6 months, 7/12 at 1 year, and 3/10 at 2 years showed persistent detectable CML cells. Intriguingly, mRNA splicing patterns changed in 5 patients following BMT, with complete loss of mRNA containing bcr exon 3 (n = 2) or new appearance of mRNA not containing bcr exon 3 (n = 2). A single patient transiently lost evidence of bcr exon 3 expression while persistently expressing the bcr exon 2/abl exon 2 splice. Our data suggest that the majority of patients harbor small numbers of malignant cells following transplantation, and that such persistence may not inevitably predict clinical relapse. Complete elimination of the malignant CML clone post-BMT may rely on immunological mechanisms (e.g., graft-vs leukemia). PMID- 1750066 TI - The role of natural antibodies in the activation of xenogenic endothelial cells. AB - Hyperacute rejection of organ xenografts is thought to be mediated by the reaction of naturally occurring antibodies and complement of the recipient with blood vessels in the donor organ. We have suggested previously that the pathogenesis of hyperacute rejection might involve the activation of endothelial cells in the graft. To evaluate the potential role of natural antibodies and complement in hyperacute xenograft rejection, sixteen human sera were tested for variation in the ability to activate porcine endothelial cells as manifested by the release of biosynthetically labeled heparan sulfate from the cells. It was then asked to which extent such variation might reflect differences in natural antibody titer and/or complement activity. The sera mediated release of 3.6-57% of endothelial cell-associated heparan sulfate. Heparan sulfate release correlated significantly with the titer, in the sera, of IgM antibodies that bound to cultured endothelial cells (P = 0.0008) or to a triad of glycoproteins believed to represent the major targets of natural antibodies in porcine to primate xenografts (P = 0.001); correlation was also observed with the total concentration of IgM (P = 0.0046). The release of heparan sulfate did not correlate with corresponding properties of serum IgG, with anti-swine hemagglutination or with isohemagglutination titers. Heparan sulfate release correlated with deposition on endothelial cells of iC3b (P = 0.0095), but not with serum complement activity. Our findings indicate that in the reaction between human serum and xenogeneic endothelial cells, it is the concentration of xenoreactive IgM and not differences in complement activity that limits the ensuing pathophysiologic events. PMID- 1750067 TI - The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity. AB - Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine. PMID- 1750068 TI - The immunosuppressive properties of enisoprost and a 5-lipoxygenase inhibitor (SC 45662). AB - Metabolic derivatives of arachidonic acid such as prostaglandins and leukotrienes may alter immune responses. Enisoprost (ENO), a synthetic prostaglandin E analog, inhibited the response of human peripheral blood mononuclear cells to phytohemagglutinin in a concentration-dependent fashion: .1, 1.0, and 10 micrograms/ml yielding 4.0, 21.7, and 74.3% inhibition, respectively. ENO also potently inhibited both IL-2 production (measured by ELISA) and IL-2 responsiveness (measured by CTLL-2 response to IL-2) in a concentration-dependent manner, yet did not inhibit acquisition of IL-2 receptors. ENO similarly diminished efferent immune function in a concentration-dependent fashion, as measured by inhibition of cytotoxic T cell and natural killer effector function. A 5-lipoxygenase inhibitor (5-LO), SC-45662, also inhibited mononuclear cell response to PHA in a concentration-dependent manner: 0.1, 1.0, and 10 micrograms/ml yielding 5.0, 9.7, and 79.7% inhibition, respectively. Although 5 LO potently inhibited IL-2 production, it had no effect on IL-2 responsiveness or IL-2 receptor acquisition. Like ENO, 5-LO impaired CTL and NK effector function yet was not as potent in inhibiting CTL effector function. In summary, ENO and 5 LO inhibit afferent and efferent immune function. The inhibitory effects of these drugs are not related to cytotoxicity as cell viability is maintained for 72 hr in the presence of these drugs, and the inhibitory effect is reversible when the drugs are removed. The 5-LO does not inhibit mononuclear cell responses simply by shunting the formation of arachidonic acid precursors to form inhibitory prostaglandins, since it does not impair IL-2 responsiveness in a manner similar to ENO. These two compounds may prove to have clinical utility in organ transplantation if safely achieved serum concentrations of these drugs yield in vivo immunosuppression parallel to our in vitro results. PMID- 1750069 TI - Detection of pancreatic islet tissue following islet allotransplantation in man. PMID- 1750070 TI - Renal transplant patients with steroid withdrawal evaluated longitudinally for their donor--specific cytotoxic T cell reactivity. PMID- 1750071 TI - The effect of meal composition on cyclosporine absorption. PMID- 1750072 TI - The renal artery resistive index and serum creatinine changes during the treatment of renal allograft rejection with the monoclonal antibody OKT3. PMID- 1750073 TI - Soluble interleukin 2 receptor and neopterin serum levels after lung/heart-lung transplantations--absence of predictive value for late allograft rejection. PMID- 1750074 TI - Production of marked prolongation of survival of canine islet xenografts in mice by antilymphocyte sera and L3T4 antibody. PMID- 1750075 TI - A technique of cervical heterotopic heart transplantation in mice. PMID- 1750076 TI - Transplantation in the mouse model--the use of a Y-chromosome-specific DNA clone to identify donor cells in situ. PMID- 1750077 TI - Problems with therapeutic monitoring of cyclosporine using silicone central venous line samples. PMID- 1750078 TI - Essential fatty acid deficiency and cardiac allograft survival in histoincompatible rats. PMID- 1750079 TI - The barrier to xenotransplantation. PMID- 1750080 TI - Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration. AB - Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS. PMID- 1750081 TI - The combi-effect--reduced rejection of the heart by combined transplantation with the lung or spleen. AB - The term combi-effect was introduced to describe the phenomenon of a reduction in rejection of heart grafts after combined transplantation with the lung. In this study in rats we investigated whether the combi-effect was an immunological process and whether it could also be induced by combined transplantation of the heart with the spleen or with a lymphocyte-depleted spleen. Heart and spleen grafts were transplanted into the abdomen; left lungs were transplanted into the thorax of recipient rats. To deplete spleens of their lymphocytes, prospective donor rats were irradiated. Cyclosporine was injected once, on day 2 after transplantation. All heart allografts transplanted alone and treated with cyclosporine were rejected acutely (median survival time [MST] of 14.5 days). In contrast, after combined transplantation of a donor lung or spleen with the heart, almost all heart grafts survived indefinitely. Transplantation of a syngeneic lung or third-party spleen had little effect on heart graft survival (MST of 22.5 days and 26.5 days, respectively). Without cyclosporine treatment, combined transplantation with a donor lung or spleen hardly prolonged heart graft survival. Transplantation of a lymphocyte-depleted spleen with the heart induced a combi-effect in cyclosporine-treated rats that was somewhat weaker: only two of six hearts survived indefinitely. We conclude that in the combi-effect an immunological mechanism reduces rejection of the heart. This mechanism is probably generated by the lymphoid tissue (bronchus-associated lymphoid tissue in lung and white pulp in spleen) in the combined transplant. PMID- 1750082 TI - Inhibition of myointimal hyperplasia and macrophage infiltration by estradiol in aorta allografts. AB - A major cause of organ graft loss after heart transplantation is accelerated atherosclerosis. In this study we used aorta allografts and investigated the effect of estradiol-17 beta treatment on both the degree of myointimal hyperplasia and morphological changes evaluated by light and electron microscopy. Outbred New Zealand white male rabbits (2.7-3.5 kg) were fed cholesterol (0.5%) from one week prior to transplantation, and until sacrifice three weeks later. The donor abdominal aorta was transplanted end-to-end to the right carotid artery of the recipient animals. Immediately following surgery, cyclosporine (10 mg/kg/d s.c.) was administered to prevent graft rejection. The allograft recipients were randomly assigned to one of five groups and treated with cottonseed oil (placebo) or estradiol cypionate at 1, 10, 100, or 1000 micrograms/kg/d i.m. for 3 weeks. The aorta grafts were harvested and fixed for transmission electron microscopy and morphometry. The area of myointimal thickening was calculated as a percent of total vessel area (mean +/- SEM); the control group was 6.6 +/- 0.5% (n = 5). Estradiol treatment significantly inhibited (P less than 0.05) myointimal hyperplasia at all doses. The values were 3.9 +/- 0.6% (n = 6) for 1 microgram/kg/day; 4.4 +/- 0.7% (n = 5) for 10 micrograms/kg/day; 3.5 +/- 0.4% (n = 6) for 100 micrograms/kg/day; and 2.9 +/- 0.1% (n = 3) for 1000 micrograms/kg/day. Electron microscopic evaluation revealed that the four doses of estradiol protected the endothelium from the degenerative changes seen in all aorta allografts from the animals in the control group. Furthermore 10, 100, and 1000 micrograms/kg/day of estradiol prevented the appearance of vacuolized macrophages (foam cells) and also the vacuolization of smooth muscle cells that was observed in the aorta allografts from the control group and the group treated with 1 microgram/kg/day of estradiol. We conclude that the inhibitory effect of estradiol on the development of graft atherosclerosis may be due to inhibition of smooth muscle cell proliferation and preservation of ultrastructurally normal endothelial cells. The inhibitory effect on foam cell production and a concomitant vacuolization of smooth muscle cells may play a lesser role. We suggest that estrogen replacement therapy may be beneficial in postmenopausal women with organ allografts. PMID- 1750083 TI - Hepatic and splanchnic metabolism of plasma proteolytic enzymes before, during, and after clamping of the hepatic artery and portal vein. AB - Parameters of the kallikrein-kinin, fibrinolytic, and coagulation systems before (control), during, and after occlusion of the hepatic artery and the portal vein were studied in anesthetized pigs. Hepatic synthesis was observed for kallikrein, plasmin, and plasminogen. The other factors, prekallikrein, kallikrein inhibitor, alpha 2-antiplasmin, prothrombin, and antithrombin-III were all released by the liver and underwent partial hepatic inactivation. The splanchnic area showed a significant synthesis of antithrombin-III. After 90 min of hepatic arterial occlusion, the hepatic release of all factors declined, and synthesis of kallikrein, plasmin, and plasminogen fell an average of 54%. The inactivation of prekallikrein and alpha 2-antiplasmin was increased and the splanchnic synthesis of antithrombin-III fell. Portal vein blood flow fell by 38%. After 15 min of portal vein occlusion (combined occlusion of the hepatic artery and portal vein) the splanchnic area started to synthetize kallikrein and the hepatic inflow of kallikrein increased by more than 50%. Splanchnic metabolism of other factors was also altered, but after revascularization of the hepatic artery changes were mostly insignificant. Hepatic synthesis of kallikrein and plasmin remained depressed after reperfusion, and that of plasminogen fell to zero. After this short period of occlusion of the hepatic artery and portal vein, plasma concentrations of prekallikrein, plasmin, and alpha 2-antiplasmin were decreased, causing a state of fibrinolysis. A role for kallikrein/bradykinin in hepatic blood flow regulation is proposed and implications of these observations for liver transplantation are discussed. PMID- 1750084 TI - The beneficial effect of a prostaglandin I2 analog on ischemic rat liver. AB - This study was undertaken to determine whether or not prostaglandin I2 (PGI2) analog pretreatment could successfully preserve organ viability after warm hepatic ischemia in rats. Although 120-min ischemia of the liver did not permit survival in rats administered normal saline solution (NS group) before warm ischemia, the survival rate of PGI2 analogue (500 ng/kg/min)-treated rats (PG group) significantly improved to 57% (P less than 0.05). Recirculation following 120-min hepatic ischemia in the NS group resulted in no improvement of B phosphorus of the ATP (B-ATP)/inorganic phosphate (Pi) ratio measured by 31P nuclear magnetic resonance, a marked increase in the serum aspartate aminotransferase (SAST) level, and an increase in the malondialdehyde (MDA) level in liver tissue. In the PG group, the B-ATP/Pi ratio was significantly improved (P less than 0.05), the elevation in SAST was also markedly suppressed (P less than 0.05), and the MDA level of the liver was lowered more than that in the NS group. Severe congestion and extensive vacuolization of hepatocytes from the peripheral to the midzonal areas were histologically exhibited with single-cell necrosis in the NS group. There were fewer histological alterations of the liver and these coincided with the changes in other parameters in the PG group. Our results indicate that PGI2 analog reduces warm ischemic injury of the liver and provides greater protection for organs to be transplanted. PMID- 1750085 TI - Correlation between high adenosine triphosphate tissue concentration and good posttransplant outcome for the canine pancreas graft after preservation by the two-layer cold storage method. AB - Assessment of viability of a pancreas graft during preservation is very important to avoid transplantation of a nonfunctioning allograft. In the present report the correlation between adenosine triphosphate tissue concentration at the end of cold preservation by the two-layer method and viability a of canine pancreas graft following transplantation was studied. After preservation by an original two-layer (Euro-Collins' solution/perfluorochemical) method (group 1) and a modified two-layer (University of Wisconsin solution/PFC) method (group 2) for 24, 48, 72, 96, and 120 hr (subgroups A, B, C, D, and E), the tissue concentration of ATP was determined using high-performance liquid chromatography, and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. Maintenance of normoglycemia for at least five days after transplantation was considered to indicate a viable pancreas graft. In group 1, functional success rates were A: 5/5, (100%), B: 4/4 (100%), C: 4/4, (100%), and D: 0/4 (0%), respectively. The ATP tissue concentrations were 7.47 +/- 0.47 (n = 5), 7.91 +/- 1.21 (n = 4), 8.29 +/- 0.21 (n = 4), and 4.94 +/- 1.11 (n = 4) mumol/g dry weight in groups 1A, 1B, 1C, and 1D, respectively. There was a statistically significant difference between viable groups (groups 1A, 1B, and 1C, 7.86 +/- 0.77 mumol/g dry weight [n = 13]) and the nonviable group (group D, 4.94 +/- 1.11 mumol/g dry weight (n = 4) (P less than 0.01). On the other hand, the functional success rates were 3/3 (100%), 3/3 (100%), 3/3 (100%), 5/7 (71%), and 0/3 (0%) in groups 2A, 2B, 2C, 2D, and 2E, respectively. Two of seven dogs died of causes related to the grafts (pancreatitis and thrombosis). The ATP tissue concentrations were 8.53 +/- 1.45 (n = 3), 9.64 +/- 1.77 (n = 3), 13.81 +/ 2.09 (n = 3), and 12.49 +/- 2.52 (n = 5) mumol/g dry weight in groups 2A, 2B, and 2C and in viable grafts in group 2D, respectively, but the ATP tissue concentration of nonviable grafts in group 2D and group E were 3.51 +/- 0.81 (n = 2) and 3.98 +/- 1.34 (n = 3) mumol/g dry weight, respectively. There was a statistically significant difference between viable groups (groups 2A, 2B, 2C and viable grafts in group 2D, 11.03 +/- 2.72 mumol/g dry weight [n = 14]) and nonviable groups (group E and nonviable grafts in group 2D, 3.79 +/- 1.06 mumol/g dry weight [n = 5]) (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1750086 TI - Evidence that adenosine is a key component in Carolina rinse responsible for reducing graft failure after orthotopic liver transplantation in the rat. AB - Recently, a rinse solution, Carolina rinse, designed to minimize reperfusion injury following liver transplantation in the rat has been developed. When used to rinse cold-stored grafts prior to completion of implantation surgery, Carolina rinse improved postoperative survival dramatically. Here we report the results of studies designed to determine the key components of Carolina rinse. Livers were explanted, stored for 12 hr in cold UW solution (0-4 degrees C), and rinsed with 15 ml of Ringer's solution immediately prior to completion of implantation surgery. In this group, 12/13 rats died within 2 days (nonsurvival conditions). In a second group, explants stored under identical conditions were rinsed with 15 ml of Carolina rinse. Carolina rinse increased average 30-day survival time significantly to over 75%. Furthermore, when grafts were rinsed with Carolina rinse lacking nicardipine or with the pH increased to 7.4, long-term survival of recipient rats was also about 75% (i.e., the modifications did not affect survival). However, Carolina rinse lost its efficacy (12% survival) when adenosine was omitted. In addition, when donor livers were rinsed with Ringer's solution containing adenosine (0.1 mM), average survival time was increased from 8% to 63%. Rinsing with Ringer's solution containing higher concentrations of adenosine (5 mM), however, did not improve survival significantly. Survival was also not improved by rinsing with Ringer's containing 0.1 mM ribose and 0.1 mM adenine, substrates for ATP synthesis that are not vasoactive. SGOT values were around 3000 U/L 1-3 days postoperatively in the nonsurviving group rinsed with Ringer's solution alone. Values were decreased over 6-fold by Carolina rinse but were not reduced significantly by Ringer's solution containing adenosine. Thus, adenosine improves survival following liver transplantation without preventing parenchymal cell injury, indicating that adenosine may work via nonhepatic mechanisms. Liver injury was also assessed by electron microscopy. After either adenosine or Ringer's rinse, sinusoidal thrombi and polymorphonuclear margination were observed together with a pattern of pericentral hepatocellular vacuolization and disruption of the sinusoidal lining characteristic of changes observed following hypoxia. With Ringer's rinse, Kupffer cells exhibited surface irregularity in pericentral regions indicative of activation. Following adenosine rinse, however, Kupffer cells appeared more flattened with less ruffling and reduced surface debris (i.e., they were less activated). Carbon uptake by Kupffer cells was also decreased significantly by Ringer's rinse when adenosine was present. Furthermore, adenosine lowered intracellular free calcium concentration in cultured Kupffer cells and improved hepatic microcirculation postoperatively. Adenosine rinse also affected extrahepatic systems: it reduced postoperative clotting time and diminished lung injury significantly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1750087 TI - Functional analysis of graft lamina propria associated lymphocytes from a recipient of a human cadaveric small bowel allograft primarily immunosuppressed with FK 506. PMID- 1750088 TI - FK 506 used as rescue therapy for human liver allograft recipients. PMID- 1750089 TI - A tuberculosis outbreak in a renal transplant program. PMID- 1750090 TI - Effect of FK 506 on islet allograft rejection in mice and pigs. PMID- 1750091 TI - Rapamycin and cyclosporine synergistically prolong heart and kidney allograft survival. PMID- 1750092 TI - Xenotransplantation in newborn goats with FK 506. PMID- 1750093 TI - The new era of immunosuppressive therapy in autoimmune diseases. PMID- 1750094 TI - The effect of FK 506 on cyclophosphamide-induced diabetes in the NOD mouse model. PMID- 1750095 TI - Prevalence of malaria in native and transmigrant populations. Effects of age and history of exposure. AB - A malaria prevalence study was performed in a village in Irian Jaya, Indonesia, that contains a population of people who have been exposed lifelong to hyperendemic malaria and another population of people who had arrived 18 months previously from areas of very low endemicity. Mean spleen sizes correlated positively with prevalence of malaria, not resistance to it. Prevalence of sexual and asexual blood stage parasites was higher in transmigrants than in the natives. The data also show that clinical resistance to malaria in this part of the world includes resistance to Plasmodium falciparum gametocytemia and that this is not the passive byproduct of a reduction in asexual parasites. This indicates that the introduction of native people into a populated malarious area will increase the percent of gametocyte carriers and may, thereby, increase the entomologic inoculation rate. PMID- 1750096 TI - Diabetes mellitus and Klebsiella pneumoniae liver abscess in adults. AB - Klebsiella pneumoniae hepatic abscess in five diabetic patients is reported. The recognition of a possible association between diabetes mellitus and pyogenic hepatic abscess, especially solitary ones, is highlighted. The clinical presentation including metastatic complications and the need for early diagnosis and institution of therapy are emphasized. Needle aspiration under ultrasonography is advocated and culture for anaerobes is stressed. PMID- 1750097 TI - Multiple faecal and urinary fistulae as a complication of native treatment of inguinal hernia. AB - A case is described of a patient who developed multiple faecal and urinary fistulae after repeated treatment for right-sided scrotal hernia by a native doctor. The patient recovered after resection of an incarcerated loop of sigmoid colon which showed fistulae with the inguinal skin and with the bladder. The bladder defect was closed. This kind of complication may be more frequent than reported. PMID- 1750098 TI - Evaluation of antibody response in meningococcal patients, contacts and vaccinees in north India. AB - Serological response was studied in a high risk age 16-30 years group, during the period December 1986-April 1988, following vaccination with a meningococcal vaccine (Biomerieux, France). A total of 200 serum samples were collected from 50 individuals before vaccination and at 1, 3 and 6 months post-vaccination respectively. Antibody response was measured by Enzyme Linked Immuno-Sorbent Assay (ELISA) and indirect haemagglutination assay (IHA). In the vaccinees antibody response by IHA test showed 56%, positivity in the pre-vaccination samples and 82%, 78% and 74% positivity 1 month, 3 months and 6 months in the post-vaccination samples. By ELISA 2%, 80%, 74% and 66% of the above groups showed serological response. Difference in the pre-vaccination and titres/O.D. of various post-vaccination groups was found to be statistically significant (p = 0.001). There was, however, no significant difference (p = 0.05) amongst the titres/O.D. of three post-vaccination groups. Similarly, acute and convalescent blood samples of 25 patients one sample each of 31 contacts was studied for antibody response. In general, higher antibody titres are produced with systemic infection than with local nasopharyngeal infection or following vaccination. PMID- 1750099 TI - Adenomyosis uteri in Ile-Ife, Nigeria. A prospective clinicopathologic study. AB - A 12-month prospective study of 120 consecutive hysterectomy and 12 myomectomy specimens received at the histopathology laboratory of the Obafemi Awolowo University Teaching Hospitals was undertaken to determine the occurrence of adenomyosis. The observed incidence was 9.8%. Adenomyosis was commonest in multiparous women in the fifth decade of life. The principal presenting complaint was abnormal uterine bleeding. The average dimension of a typical affected uterus was 10 x 7 x 6 cm weighing an average of 175 g. Diagnosis was mostly post operative. This study shows that adenomyosis uteri is not uncommon in Nigerians. PMID- 1750100 TI - A hospital outbreak of cholera in Dhaka, Bangladesh. PMID- 1750101 TI - Serum ferritin and cholera. A prospective study. AB - An association has been shown between iron deficiency and a low gastric acidity while the latter is known to increase susceptibility to cholera. This study was undertaken to ascertain whether iron deficiency is a risk factor for contracting cholera. The subjects were 60 adult males-30 with cholera admitted to ICDDR,B and 30 controls matched for age, sex and socio-economic status from the same household or immediate neighbourhood of the index case. Fingerstick blood was taken from all subjects to estimate the haematocrit, and serum ferritin concentration by an ELISA. The mean ferritin level of the study group was 38.7 ng/100 ml, in the controls. There was a significant difference in the serum ferritin level between the groups (P less than 0.005), Wilcoxon Sign Rank test for matched pairs suggesting that cholera patients tend to have lower serum ferritin concentration. Further prospective studies are required to define the possible association between iron deficiency and cholera more accurately. PMID- 1750102 TI - Chloroquine therapy still useful in the management of malaria during pregnancy in Muheza, Tanzania. AB - In searching for effective malaria chemosuppressives during pregnancy in Muheza District--Tanzania, pregnant women are randomly given either 300 mg base chloroquine once weekly or 200 mg daily proguanil. Breakthroughs presenting with clinical malaria are treated with 25 mg base chloroquine/kg (25 CQ) over three days. Due to loss of malaria immunity during pregnancy and Muheza moderate levels and degrees of chloroquine resistance, the in vivo response to 25 CQ was monitored. Between March and May 1989, 49 women were treated resulting into 32 (65%) parasitological clearances and 17 (35%) failures within 7 days. Two of 17 failures (12%) exhibited RIII response and the remaining 15 (88%) had a favourable clinical response. Only 6 (19%) of 32 cleared patients either recrudesced or got reinfected during the three weeks follow up period. In addition to its safety and affordability, the observed drug efficacy during peak malaria transmission and inspite of prevailing resistance makes 25 CQ an ideal first line drug for the management of malaria during pregnancy. PMID- 1750103 TI - Parasitic infections in young Jamaicans in different ecological zones of the island. AB - Data are presented for the first country wide prospective study on gastrointestinal tract parasitic infections done in Jamaica. Samples from 2,947 young Jamaicans drawn from all ecological zones and from all parochial divisions of the island were analyzed. Pica was practised by 8.6%. Generally, prevalence of organisms was as follows: Trichuris trichiura (12.3%), Ascaris lumbricoides (9.5%), hookworm (2.2%), Strongyloides stercoralis (0.3%), Giardia lamblia (6.3%) and Entamoeba coli (7.7%). Several other spp. of protozoans were recorded. Prevalence of A. lumbricoides, T. trichiura and Necator americanus was significantly greater in upland than in lowland (both urban and rural), while the situation was reversed for G. lamblia-infections. Greatest variations were age related. A. lumbricoides and T. trichiura reached peak prevalence of 15.3 and 20.5% respectively in 5-9-year-olds, while hookworm peaked later at 15-19 years of age. Suggestions are made for a national and even regional antihelminthic program for the mass treatment of pre- and primary school age children. PMID- 1750104 TI - Studies on a focus of yaws in the Santiago Basin, province of Esmeraldas, Ecuador. AB - A clinical and serological epidemiological study done on a yaws focus in the Santiago Basin area, province of Esmeraldas, showed a prevalence of 11.3% for active clinical lesions and a seropositivity of 94.9%. The Rio Santiago was hyperendemic for yaws (prevalence, 17.9%; seropositivity, 98.0%) while Rio Zapallito was found to be mesoendemic and the Rio Cayapas and Rio Onzoles hypoendemic. Active and latent evidence of yaws was found only in the black race. Children, ages 5-12 year, were found to have the highest incidence (55.8%) of clinical lesions, with the majority found on the legs (64.2%). Papilloma was the most prevalent lesion (55.4%). Mass treatment of the basin using benzathine penicillin G was done according to WHO recommendation. PMID- 1750105 TI - Epidemiology of common transmissible skin diseases among primary school children in north-west Ethiopia. AB - A total of 1842 school children were examined for the occurrence of common transmissible skin infections in a rural area in North-West Ethiopia. The result showed a prevalence rate of 49.2%. Tinea capitis, impetigo, infected wounds and verrucae vulgaris were common. In addition the overall prevalence rate of lice infestation was 55.4%. The findings indicated the need to develop appropriate intervention programmes both at school and community levels. PMID- 1750106 TI - Hepatic dysfunction in undernourished patients receiving isoniazid and rifampicin. AB - Adult undernourished tuberculous patients receiving isoniazid, rifampicin and ethambutol were evaluated clinically and biochemically for hepatic dysfunction. The nutritional status was assessed by body-mass index, serum albumin and haemoglobin. While only 11% of the patients developed jaundice, the majority of the patients had a significant elevation of the serum hepatic enzymes suggesting subclinical hepatotoxicity. A significant downward trend during the 3-6 months period was seen in patients with multiple estimations of SGOT and SGPT indicating a self-limiting toxic process. However, the continued elevation of GGT suggests enzyme induction by rifampicin. Undernutrition contributes to drug toxicity by various mechanisms. Therefore, it is important to evaluate the nutritional status of the tuberculous patients receiving drugs, which are potentially hepatotoxic. PMID- 1750107 TI - A study of group B streptococcal carrier state during late pregnancy. AB - The carriage of Group B Streptococcus was investigated in 500 females in the third trimester of their pregnancy by culturing vaginal and rectal swabs and urine collected from each patient. A high rate of colonization was noted since 152 cases (30.4%) were found to harbor the organism, and 219 specimens (48%) from a total of 456 collected from these 152 cases were positive for Streptococcus agalactiae. Of the 219 positive specimens, 94 (42.9%) were vaginal swabs, 90 (41.1%) were rectal swabs and the remaining 35 (16%) were urine specimens. It is recommended that vaginal and rectal swab culture be used to detect carriers of group B streptococci, since using such a combination in this study revealed 91.4% of all positive cases. PMID- 1750108 TI - Lack of relationship between sorghum consumption, mycotoxin contamination and pellagra in a traditionally sorghum eating population. AB - Traditionally, the disease pellagra has been associated with corn consumption and niacin deficiency, and has presently been recognised as a multiple factor nutritional syndrome. In the recent past, it has been suggested that consumption of mycotoxin contaminated sorghum/corn may be involved in the development of pellagra in a sorghum/corn eating population. The present study relates to the assessment of levels of mycotoxins (aflatoxin B1 and T-2 toxin) in sorghum collected from a traditionally sorghum eating population. Despite 25% fungal contamination in the sorghum samples collected, the levels of mycotoxins were minimal (1.4%) and there was no incidence of pellagra in the survey area. The absence of pellagra in the survey areas may be attributed to the changing dietary pattern. PMID- 1750109 TI - Surveillance of patients attending a rural diarrhoea treatment centre in Bangladesh. AB - In May 1983, a surveillance system was set up at a rural diarrhoea treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) to study a 20% systematic sample of all admissions. Between May 1983 and April 1984, 2,635 patients were studied. A recognized enteric pathogen was detected in 69% of the patients screened, 15% of whom had a mixed infection. Vibrio cholerae 0: 1 was the most common enteropathogen detected (39%), followed by enterotoxigenic Escherichia coli (ETEC) (14%), Shigella spp. (11%), and Campylobacter jejuni (11%). Detection of C. jejuni was highest in infants, Shigella spp. in children between 1-4 years and V. cholerae 0:1 in children between 3-9 years of age. 75% of patients presented with watery diarrhoea, a presentation that was significantly more common in patients infected with V. cholerae 0:1 (94%) and ETEC (88%). Bloody diarrhoea was the presenting complaint in 18% of all patients, but in 65% of patients in whom Shigella spp. was isolated. Although 91% of patients reported that they had prior experience of use of oral rehydration therapy (ORT), 54% of the patients came to the treatment centre with no or mild dehydration and more than half of them did not use ORT before coming to the treatment centre. Most of these patients could have been safely treated at home if ORT could be made available and acceptable. PMID- 1750110 TI - Haematologic indices in African children. AB - A full blood count was performed on 380 children (186 preschool and 194 school children). It was found that the school children had significantly higher haemoglobin, haematocrit, neutrophil and platelet counts than the preschool children. The preschool children had higher total leucocyte and lymphocyte counts. PMID- 1750111 TI - Glucose-6-phosphate dehydrogenase variants and sickle cell genes in Al-Qunfuda, Saudi Arabia. AB - This study was conducted on 823 male and female subjects to determine the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell gene in Al-Qunfuda, a densely populated and malaria endemic region in western Saudi Arabia. The results show the presence of both sickle cell and G-6 PD deficiency genes in this population. The prevalence of Hb S heterozygotes in the total population was 18.93% and that of homozygotes was 2.02%. The gene frequency of sickle cell gene was 0.121. G-6-PD-B+ was the normal enzyme and occurred at a frequency of 83.60% and 78.46% in the male and female population, respectively. G-6-PD variants identified included G-6-PD Mediterranean, G-6-PD A+, G-6-PD-A- and G-6-PD-Mediterranean-like. The frequency of each variant in the male and female population was 10.65% and 9.74% for G-6-PD-Mediterranean, 2.30% and 1.53% for G-6-PD-A+, 0.46% and 0.51% for G-6-PD-A- and 3.0% and 9.74% for the G-6-PD-Mediterranean-like variants, respectively. No significant interaction between sickle cell and G-6-PD genes could be demonstrated. PMID- 1750112 TI - Inpatient or outpatient initiation of insulin therapy. Experience and cost effective analysis in a suboptimal clinical setting. AB - In diabetic day-care centres insulin therapy is started on an outpatient basis. However, in areas where such centres are non-existent, diabetics are admitted to hospital for initiation of insulin therapy. As an alternative to this practice, insulin was initiated in 53 outpatients in a suboptimal clinical setting to find out if it is safe, feasible, acceptable and cost-effective. Fifty-one diabetics, admitted for initiation of insulin, served as controls. No significant difference was found in the mean blood glucose before and after treatment, insulin requirement and response to treatment in both groups. Cost analysis showed that outpatient treatment was cheaper than inpatient treatment at third class and indicated a saving of US $273.00 per patient; these costs were much higher for those admitted to expensive classes. None of the outpatients had hypoglycaemia or ketoacidosis during the study period. Thus, outpatient insulin therapy is safe, feasible, acceptable and cost effective; it could be adopted even in places with suboptimal clinical setting. PMID- 1750113 TI - Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies. AB - The red powdery extract from the seeds of the annatto, Bixa orellana, is a well known food colouring. In an oil suspension it is used as a folk remedy (bush tea) in the West Indies, for diabetes mellitus. Detailed investigations on this extract, yielded a methyl ester, trans-bixin, molecular weight 394 and molecular formula C24H30O4. This purified substance was demonstrated, in anaesthetised mongrel dogs, to cause hyperglycaemia. Concomitant electron microscopy of tissue biopsies, revealed damage to mitochondria and endoplasmic reticulum mainly in liver and pancreas. When dogs were fed on a diet fortified with riboflavin, there was neither demonstrable tissue damage nor associated hyperglycaemia. These findings point to: (i) the potential dangers of informal medications such as 'bush teas'; (ii) the possible role of plant extracts/food additives in the development of diabetes mellitus especially in the undernourished state. PMID- 1750114 TI - The pattern of malignant disease in north east Nigeria. AB - This paper is a retrospective review of the 780 admissions with malignancy to the University of Maiduguri Teaching Hospital over a five year period, 1983-1987, carried out to determine the type of malignancies presenting and their relative frequencies and to compare this with the rest of West Africa. The commonest tumours were primary liver cell carcinoma with a proportional frequency of 17%, carcinoma of the breast (8%) and bladder (7%). There is a lower incidence of trophoblastic carcinoma (0.3%) than might be expected and a higher incidence of nasopharyngeal carcinoma (8% of male tumours). Carcinoma of the stomach and colorectum are uncommon. The possible reasons for this are discussed. PMID- 1750115 TI - Coronary heart disease and coronary risk profile in a primitive population. AB - A study of coronary heart disease and risk factors was conducted in a total Sri Lankan aboriginal population who face imminent extinction due to developmental programmes in the vicinity of their jungle homelands. Coronary heart disease was not detected among the aborigines. Hypertension was present in 5.7% of males and 1.9% of females. 39% of males smoked. Serum cholesterol, triglyceride and high density lipoprotein cholesterol levels were 5.25 mmol/l (SD 0.45), 1.99 mmol/l (SD 0.92) and 1.2 mmol/l (SD 0.2) respectively. Obesity was not seen and the level of physical activity was high. The rarity of coronary heart disease could be attributed to this favourable coronary risk profile. PMID- 1750116 TI - Pattern of upper gastrointestinal disease in the eastern province of Saudi Arabia. Endoscopic evaluation of 2,982 patients. AB - The records of 2,982 patients who were subjected to upper gastrointestinal (UGI) endoscopy were retrospectively analyzed. All patients were seen at King Fahd Hospital of the University, Al-Khobar during the period 1982-1986. All were adult patients with a mean age of 46 years, of whom two thousand nine (67.4%) were males. The commonest endoscopic diagnosis was chronic gastritis (21.4%) followed by duodenal ulcer (17%) and chronic oesophagitis (11.7%). Of 1,256 biopsied patients a 'histologically normal' diagnosis was obtained in 565 (45%) from all sites. However, chronic non-specific superficial gastritis (22.6%) followed by chronic duodenitis (17.5%) constituted the two commonest histological diagnoses. Helicobacter pylori was identified histologically on the gastric mucosa of 72% of patients with superficial chronic active gastritis, with or without associated peptic ulcer disease. Duodenal ulcers followed by oesophageal varices were the two commonest diagnoses encountered in 200 patients presenting with UGI bleeding. These results are discussed and compared to those of other studies. PMID- 1750117 TI - The prevalence of symptoms of dyspepsia in north eastern Nigeria. A random community based survey. AB - In a randomised household survey of 620 people in rural north eastern Nigeria there was a 26% six month prevalence of dyspepsia in adults and a 6% prevalence amongst teenagers. Dyspepsia was associated with the intake of alcohol (p less than 0.0054) and Cola nut (p less than 0.00013). The prevalence increased with age; the mean length of history was nearly four years and over half of the subjects with dyspepsia had sought medical advice, mainly from traditional healers. 12% of a similar group of hospital patients with dyspepsia were previously found to have peptic ulceration, suggesting that the community prevalence for peptic ulceration is 18/1000. This is lower than found in the 'West'. PMID- 1750118 TI - Poliomyelitis control by annual immunization campaigns with oral polio-virus vaccine in a rural area of India. AB - The effectiveness of Oral Polio Vaccine (OPV) delivered in annual immunization campaigns in reducing the prevalence of poliomyelitis was evaluated in January 1989 by conducting a sample survey in 66 villages in Northern India with a population of 42,000. The prevalence of residual paralytic poliomyelitis was 13.4 per 1,000 children born during 1974-1978; this is 2.7 times higher than the rate of 5.0 per 1,000 born in 1979-1983 and 9.6 times higher than the rate of 1.4 per 1,000 born during 1984-1988. The marked decline in disease prevalence in recent years may be related to the rise in OPV immunization. The vaccination rate was less than 26% before 1978, 38-75% during 1979-1983 and 77-89% during 1984-1987. The annual immunization strategy can be used to control poliomyelitis in developing countries where the health care infrastructure is not well developed. PMID- 1750119 TI - Reactivation of Chagas' myocarditis during therapy of Hodgkin's disease. AB - A 46-year-old female patient with chronic Chagas' myocarditis without heart failure was submitted to chemotherapy because of Hodgkin's disease. During treatment the frequency of polymorphic ventricular extrasystoles raised and the patient died by a sudden cardiac arrest. Autopsy revealed chronic Chagas myocarditis with an acute exacerbation. Nests of amastygotes with a density of up to 14 pseudocysts/cm2 were found in the myocardium, although restricted to the septum and left ventricular posterolateral wall. Extensive histologic examination did not reveal parasites in other locations. This favors the concept of a localized exacerbation of Chagas' disease due to immunosuppression developing from a persistent parasitic focus in the heart. Although this reactivation during chemotherapy of malignant disease is rarely reported in literature, a careful monitoring of patients with positive Chagas' serology during chemotherapy is recommended. PMID- 1750120 TI - Rice-ORS shortens the duration of watery diarrhoeas. Observation from rural Bangladesh. AB - In rural Bangladesh, standard glucose based oral rehydration salt (glucose-ORS) and rice based oral rehydration salt (rice-ORS) were compared as domiciliary treatment for watery diarrhoea. Using identical supply systems, packaged glucose ORS was provided in one area and packets of rice-ORS in another. Mothers of under five children in each area were trained in the preparation and use of the respective ORS. A third area, where no ORS was provided from the study source, served as comparison. In two years of surveillance and follow-up about 10,000 diarrhoeal episodes were detected in each area, approximately one-third of which were watery diarrhoea. Rice-ORS alone was used to treat 74% of these episodes and glucose-ORS alone for 65% of the episodes in the respective areas. Drugs were the main treatment regimen used in the comparison area. Results of the study showed that rice-ORS treated episodes of watery diarrhoea ended with shorter duration (median duration 2 days vs. 4 days) and fewer hospitalisation (0.1% vs. 0.5%) compared to those treated with glucose-ORS. These differences were statistically significant. But, diarrhoeal mortality was unaffected by the use of either ORS under the study situation. PMID- 1750121 TI - Severe clinical nutritional neurological damage in a young Nigerian detainee. AB - The case of a 22-year-old Nigerian detainee with features of severe clinical malnutrition, is reported. Within 2 years of prison confinement and undernutrition, he developed features of severe malnutrition, with severe sensory and motor neuropathy of the lower limbs, and pulmonary tuberculosis. Despite intensive nutritional rehabilitation, patient did not regain the use of his lower limbs. The initial economic constraint in the management is highlighted. PMID- 1750122 TI - Adenosquamous carcinoma of the stomach. With a note on pathogenesis. AB - A case of the rare adenosquamous carcinoma of the stomach is presented. This unusual type of stomach tumour is the first such case to be reported in Jamaica and in the Commonwealth Caribbean. We provide evidence in support of the metaplastic derivation of the squamous component from an existing adenocarcinoma. PMID- 1750123 TI - Felty's syndrome in a Nigerian. AB - The first case of Felty's syndrome to be reported in a Nigerian, a fifty five year-old woman who developed splenomegaly and leukopenia during the course of strongly seropositive rheumatoid arthritis of ten years duration is presented. her arthritis had lasted for about ten years, but she did not have the severe deforming disease known to be associated with Felty's syndrome. Radiologically there were no erosions and subcutaneous nodules were absent. She had a positive granulocyte specific anti-nuclear factor, cryoglobulins containing IgA and IgM and her polymorph-nuclear granulocytes showed evidence of impaired killing of staphylococci. PMID- 1750124 TI - Default and non-compliance among adult epileptics in Zaria, Nigeria. The need to restructure continued care. AB - Forty five epileptics were observed for non-compliance or default over 2 1/2 years. There were 39 episodes of non-compliance among 19 patients. Six patients had 3 or 4 episodes of non-compliance. Thirteen patients gave their reasons as non-availability of drugs or excessive cost of drugs. Drowsiness or confusion over drug dosages was the reason given by 3 others. Three other patients unilaterally suspended medication. Eighteen patients had defaulted. Twelve of them were males. Three had defaulted after only a single clinic attendance. Seizures in 9 patients were in temporary control immediately prior to default. It is suggested that otherwise well epileptics should be managed in their local community. As a matter of urgency governments need to provide drugs at subsidised rates and provide a mechanism for distributing them efficiently. PMID- 1750125 TI - Immunological response to Helicobacter pylori among Nigerians. AB - Among 420 Nigerians examined, 39% had antibodies to Helicobacter pylori. The prevalence was significantly higher in males (55%) than in females (29%). The prevalence tended to rise with age in both sexes and was significantly higher in the 30-34 years age group. Socio-economic class and rural dwellage did not affect the prevalence. The study may indicate that H. pylori is endemic in Nigeria. It also shows that the detection of antibodies to H. pylori may be a rapid and cheap method for diagnosing H. pylori infection in developing countries where sophisticated equipment for detecting this organism is not available. PMID- 1750126 TI - Urinalysis and electrolyte profiles in patients with acquired immunodeficiency syndrome. AB - One hundred and twenty six patients diagnosed as having AIDS had their urinalysis and electrolyte profiles studied. The commonest electrolyte abnormalities were a low serum bicarbonate in 56% of the patients and hyponatraemia in 48%. Possible aetiological factors are discussed. Significant pyuria was found in 10% of the patients and significant bacteriuria in 13%. Escherichia coli was the commonest isolated organism (56% of all the culture positive cases). Proteinuria above the upper limit of normal was detectable in 13% of the patients; of these, 25% had proteinuria in the nephrotic range. Of the patients 3% had clinical and biochemical evidence of renal insufficiency. It is concluded that significant bacteriuria occurs commonly in AIDS and that renal insufficiency and nephrotic syndrome may be associated with the disease. It is also noted that other electrolyte and acid-base abnormalities, in particular hyponatraemia and low bicarbonate levels may contribute to the morbidity and mortality in patients suffering from AIDS. PMID- 1750127 TI - Human immunodeficiency virus type 1 infection in a community of southern Mozambique. AB - We report the results of a study held between 1986 and 1988 on a population constituted by 493 subjects (425 of Mozambican nationality) all living in the camp organized for the building of the dam in Corumana (Sabie district, Maputo). We found five subjects, all of them from Mozambique, seropositive for HIV-1 antibodies (ELISA and WB) with a prevalence of 1.2%. Four of the positive samples came from female subjects (1.7% of 239 females tested); one positive sample came from a male subject (0.5% of 186 tested). PMID- 1750128 TI - Food intake and socioeconomic status in children in northeast Thailand. AB - To assess the food intake and to evaluate the relationship between socioeconomic status (SES) and food consumption of northeastern Thai children a dietary survey was carried out among 108 urban and rural 3-8-year-olds in Sakon Nakhon province. Energy and nutrient intakes were assessed by the 24 hour recall method and calculated with local food consumption tables. Urban children consumed significantly more eggs and products containing animal proteins than rural children. In urban areas the percentage of users of meat, eggs, and fruit was significantly higher than in rural areas; fish was consumed more frequently in rural areas. As compared with the FAO/WHO RDA (Recommended Daily Allowances) all children showed a very inadequate supply of energy, calcium, iron (except urban children), vitamin A, thiamin, riboflavin, and niacin. The mean daily protein intake was almost equal to or higher than the calculated requirements. Children of lower socioeconomic background showed a lower fat intake, a lower contribution of fat to the energy intake, and a higher contribution of carbohydrates to the energy intake than children from families with a higher SES. This study shows that nutrient intakes far below recommended intakes are common among the examined northeastern Thai children and of a serious nature, and that much more emphasis needs to be given to increase the energy or food intake rather than the protein content of their grossly inadequate diets. PMID- 1750129 TI - The use of plasma fructosamine in the assessment of diabetic control. AB - Plasma fructosamine and glycosylated haemoglobin were measured in insulin dependent (n = 30) and in non-insulin-dependent diabetics (n = 90) and in healthy controls (n = 45). Fructosamine correlated significantly with glycosylated haemoglobin in the non-insulin dependent (r = 0.5, P less than 0.001) better than in the insulin-dependent group (r = 0.39, P less than 0.05). No correlation was found between plasma fructosamine and albumin or total protein concentrations when the concentrations of albumin and protein are within normal reference range. The fructosamine test has got many desirable characteristics, which will give it a role in the assessment of diabetic control. PMID- 1750130 TI - Plasma lipids and lipoproteins in type II diabetic Nigerians with retinopathy. AB - Derangements in plasma lipids and lipoproteins have been observed in Caucasian diabetics with retinopathy, a major microvascular complication of diabetes mellitus. The role of plasma lipids and lipoprotein in the development of diabetic retinopathy is not clear and its alteration in black Africans has not been investigated. Fasting plasma cholesterol, triglyceride and HDL-cholesterol concentrations were estimated in 27 Type II (non insulin-dependent) Nigerian diabetics with retinopathy and 37 without retinopathy and 63 healthy subjects. Both diabetic subgroups were comparable regarding their blood glucose control, body mass index and duration of diabetes. Plasma lipid and lipoprotein concentrations were similar in each group of patients, with no significant differences in diabetics with and without retinopathy. Plasma lipids and lipoproteins were not affected by the duration of the diabetic state. These results suggest that diabetic retinopathy in Nigerians is not associated with significant alteration in the concentration of plasma lipids and lipoproteins. PMID- 1750131 TI - Nasopharyngeal carcinoma. A comparative study. AB - A comparative study of Ghanaian and Saudi hospital cases of nasopharyngeal carcinoma (NPC) shows a higher occurrence among younger subjects in the Ghanaian group, with the peak age incidence in the Saudi group being similar to those reported from other parts of the world. In view of the known high prevalence of Burkitt's lymphoma among Ghanaian children, it is suggested that the much higher proportion of younger Ghanaian subjects with NPC may be related to early exposure to the Epstein-Barr virus which is known to be associated with both malignancies. PMID- 1750132 TI - Histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease) in Saudi Arabia. AB - Five cases of histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease) are described. As the condition appears to be poorly recognised in Saudi Arabia, an extensive review of the histological features is presented, in order to improve pathologists' awareness and to minimise the risk of diagnosing prognostically less favourable conditions such as malignant lymphoma. Etiologic and pathogenetic features of the disease are also discussed. PMID- 1750133 TI - An effective and safe surgical method for the treatment of hydatid cysts of the liver in children. AB - Between June 1986 and May 1989 35 children (18 boys and 17 girls) below the age of 12 years were surgically treated for hydatid cysts of the liver. Of the children 24 (68.5%) had a single cyst situated in either of the lobes of the liver, while the remaining 11 (31.5%) harboured more than one cyst. A uniform method of enucleation, partial cystectomy and external tube drainage was used in all of them. Small residual cavities were not drained but were kept open on to the surface of liver. Results showed that six patients (17.1%) had transient biliary discharge which resolved within 3-6 days, whereas in two children (5.7%) biliary drainage persisted for four, respectively six weeks following surgery. This also stopped spontaneously. The method we used in our patients was safe and effective. PMID- 1750134 TI - Attitudes and behaviour of physicians towards smoking in Riyadh city, Saudi Arabia. AB - In Riyadh city 698 physicians were studied for their smoking habits, attitudes and behaviour; 48% were smokers and 34% are currently smoking. Males smoked significantly more than females currently and in the past. Smoking prevalence and intensity tended to decrease with age and quitting periods were longer. More than 60% of the physicians agreed that smoking is a major contributing factor in the causation of coronary artery disease, lung cancer and chronic bronchitis; less than 20% said the same for bladder cancer and neonatal death. Setting a good example for children was the most important reason for not smoking. PMID- 1750135 TI - The problem of trauma in Nigeria. Pattern as seen in a multicentre study. AB - Between 1982 and 1984 a multicentre study of trauma was conducted at the University of Ilorin Teaching Hospital (UITH) and eight other hospitals receiving patients from four states adjoining Kwara State of Nigeria. Average trauma admissions ranged between 4.3 and 20.6% of total admissions while 2.4% of dam construction workers sustained injuries. Peak trauma incidence and operations occurred in the third decade of life, followed road traffic accidents (RTA's) and involved males. Most outpatient trauma activity occurred on Saturdays while trauma admissions were highest on Mondays and Wednesdays. Trauma mortalities in the hospitals appeared to reflect severity of trauma encountered. PMID- 1750136 TI - Jimson weed food poisoning. An epidemic at Usangi rural government hospital. AB - Ten agitated and psychotic patients were admitted to Usangi hospital after having eaten stiff-porridge (Ugali) made from millet (Serena). This had been bought from the local regional branch of the National Milling Corporation (NMC). The patients had cardinal signs of atropine poisoning, viz., psychosis with hallucinations, tachycardia, fixed dilated pupils and a dry mouth. Toxicological analysis of the food samples revealed contamination with Jimson weed (Datura stramonium) seeds which contained an atropine-like alkaloid. On studying the records of the chief government chemist, it was found that a similar type of food poisoning had occurred in at least eight other regions. The clinical picture and management of this entirely preventable type of agricultural food poisoning are discussed. PMID- 1750137 TI - Two cases of ocular leishmaniasis. AB - Two cases of cutaneous leishmaniasis with ocular involvement are presented. The diagnostic difficulty, the possible complications and the importance of a correct diagnosis of such cases is discussed in the light of the cases presented and of previous similar case reports. PMID- 1750138 TI - Sickle cell-thalassemia in a Jordanian family. AB - A family case report of sickle cell-thalassemia syndrome shows three problems concerning this disease. Firstly, the problem of differentiating sickle cell thalassemia from the sickle cell disease; secondly, the wide range varieties in clinical picture; thirdly and finally contradiction in the criteria of prognosis. In this report sickle cell-thalassemia case was confirmed by constructing a hemoglobin electrophoresis pedigree for the patient. Clinical varieties and prognosis of sickle cell-thalassemia in this family are discussed. PMID- 1750139 TI - [Rheumatic manifestations in human immunodeficiency virus (HIV) infection]. PMID- 1750140 TI - [Caries prophylaxis by fluoride, is it necessary in Tunisia?]. PMID- 1750141 TI - [Biochemical approaches in states of urinary proteins]. PMID- 1750142 TI - [The role of echography in the diagnosis of extra-uterine pregnancy]. PMID- 1750143 TI - [Digestive hemorrhages in the cirrhotic patient]. PMID- 1750144 TI - [Resuscitation of drowning patients]. PMID- 1750145 TI - [AIDS and tuberculosis in central Tunisia]. PMID- 1750146 TI - [Role of ultrasensitive detection of TSH and free thyroxine in the surveillance of primary treated hypothyroidism (79 cases)]. PMID- 1750147 TI - [The contribution of tomodensitometry in the evaluation of hypopharyngeal esophageal cancer metastasis]. PMID- 1750148 TI - [Current role of anterior sero-myotomy associated with posterior vagotomy (Taylor operation) in the treatment of chronic duodenal ulcer]. PMID- 1750149 TI - Energy-loss near-edge fine structure and compositional profiles of cryomilled oxide-dispersion-strengthened aluminum. AB - Spatially resolved electron energy-loss spectroscopy (SREELS) makes possible the identification of small second-phase particles in an oxide-dispersion strengthened aluminum alloy produced by mechanical alloying in a liquid-nitrogen slurry. Near-edge fine structure profiles based on aluminum L23 features that are characteristic of Al-Al or Al-O bonding yield the metal/oxide fraction as a function of probe position. Profiles of nitrogen fraction are derived from linear sequences of spectra so that detection limits can be analyzed at each point in a scan. Quantitative analysis of these linear profiles shows that particles with diameters in the range 10 to 30 nm are rich in nitrogen. A combination of statistical analysis of background removal results with visual inspection of derivative spectra is used to estimate detection limits. PMID- 1750150 TI - Algorithms for Bayesian background-subtracted Fourier darkfield imaging. AB - Formal consideration of prior information on the Fourier amplitude of background contrast in an image, using the same Bayesian principles of statistical inference which underlie thermodynamics, allows one to subtract background without favoring only selected parts of frequency space. Without the bias in frequency space which causes periodicity bleeding and mars literal interpretation of Fourier-filtered images, the shape transform of aperiodic objects can be left intact. Algorithms for Bayesian background subtraction from one- and two-dimensional images are presented which further consider, in ad hoc fashion, one's uncertainty about background amplitude. The results help explain the reported success of Fourier truncation, and indicate that Bayesian background-subtracted images can minimize root-mean-square image error, as well as periodicity bleeding, in comparison to Fourier-filtered and Fourier-truncated alternatives. PMID- 1750151 TI - [Nursing insurance. Insurance responsibility or responsibility insurance?]. PMID- 1750152 TI - [Meaning of the "scientific validity clause" of private hospital insurance (section 5/1 f MB/KK 76). With reference to recent verdicts]. AB - As per Section 5/1 f of the classic conditions 1976 of the "Association of private health insurance carriers" (Verband der privaten Krankenversicherung), benefits won't be paid for methods of examination or treatment and remedies which are from the scientific point of view generally not recognized. Basic reflections have led to the fact that today the term "scientifically recognized methods" and the term "traditional medicine" will be treated as equivalent. Contrary verdicts, according to which treatments on the basis of anthroposophic medicine or by means of electro-acupuncture by Voll would be considered as generally recognized medicine from the scientific point of view and would have to be paid by the private health insurance carriers, are consequently not comprehensible. Supposing that the trend continues that private health insurers have to pay more and more expenses incurred for all kind of outsider-methods, this would lead not only to a great drain on the purse of the private health insurance carriers, but have also unpleasant consequences for the whole medicine, because the uniformity of the medicine is endangered. To take steps against has not only to be the task of the private health insurance carriers, but it is also in the interest of the physicians and, at last, of the patients, too. PMID- 1750153 TI - [Alternative therapy. Chances in Bechterew disease?]. AB - The Bechterew disease is inherited but the illness is triggered by outer influences. We are therefore not able to do causal treatment. In consequence a lot of alternative remedies like the extract of Thymus and Vitamin E have been tried. If the Bechterew disease shows more or less an ossifying progress they do not show any effect. If the issue is inflammatory Vitamin E could act as radicalintercepter. The extract of Thymus is only a placebo. PMID- 1750154 TI - [Risks of electromagnetic fields for humans]. AB - Different kinds of electromagnetic fields are treated regarding their possible effects on the human organism. Only scientific findings are taken as a basis for these considerations. According to the latest state of research only strong magnetic fields of low frequency and strong electromagnetic fields of high frequency can be critical for humans if exposed for a prolonged period. Possible causes for this threat are either the incidence of heart fibrillation or grave burnings of the body. Fields with such a strong intensity, however, are found only in few specific technical environments where they usually can be avoided by the specialists there. An impairment of well-being may also occur in connection with almost all other kinds of fields due to direct or indirect influence when the strength of the field becomes very high. An exception to that is only the static magnetic field where there are different findings from in-vivo- as well as in-vitro-experiments which, however, do not fit into these categories. Since the mechanisms of these effects are not understood yet, it is impossible to make statements about the medical relevance of the observed effects. Considering the variability and the partial inconsistency of the results found in magnetic fields it must be concluded that additional studies are necessary to validate these findings statistically. Last not least this also applies to the presumed and in public controversially discussed connection between the promotion of cancer and relatively weak time-varying magnetic fields, which in these low intensities occur not only in households, cars and trains, but also in almost all working environments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750155 TI - [Heart damage after electric injury]. AB - Death from electrical accident due to low voltage (220 Volt/380 Volt) is usually caused by ventricular fibrillation. In humans who sustain non fatal electrical injury abnormal ECG findings due to myocardial damage are rare. 243 (76%) of 320 ECGs of survivors of an electrical accident were diagnosed as normal. In 42 patients (13%) unspecific electrographic changes were seen and in 35 (11%) abnormal ECGs were found. In comparison to findings in normal populations no significant accumulation of ECG changes was observed. A causal relationship between abnormal ECG findings and electrical accident is only then probable if ECG abnormalities are documented immediately after injury and serial ECG controls demonstrate significant changes in comparison to the initial abnormality. PMID- 1750156 TI - [Arteriosclerotic plaque rupture. Its significance for myocardial infarct, sudden heart death and unstable angina]. AB - In coronary heart disease ruptures of atherosclerotic plaques have a key position. As a rule plaque fissuring develops in the fibrous cap of a complex atherosclerotic plaque with necrotic core. In myocardial infarction in nearly all cases mural or occlusive thrombi develop as a consequence of plaque ruptures. In instable angina, too, plaques with ruptured surfaces are very numerous but often thrombi are smaller than in patients dying from myocardial infarction. Also in cases of sudden death plaque fissurings are frequently observed. Dynamic thrombi covering plaque ruptures may be sources of microemboli in the myocardium. PMID- 1750157 TI - [Intermittent claudication]. AB - The symptom of intermittent claudication indicates a generalised arteriosclerosis. The high mortality of these patients is due to myocardial infarction, cerebrovascular events and rupture of aortic aneurysms. Prognostic factors for the progression of peripheral occlusive arterial disease to rest pain and trophical lesions are persistent nicotine consumption, arterial occlusions on more than one extremity, brachiopedal pressure quotient less than 0.5 and diabetes mellitus. Therapy of choice in most cases is the walking exercise. When the claudication distance remains very short or decompensation of peripheral circulation is imminent, reopening procedures like percutaneous transluminal angioplasty should be performed. If they are successless a prostanoid therapy is able to relief the complaints. PMID- 1750158 TI - [Diagnosis and prognosis of carotid artery stenosis]. AB - The diagnosis of a carotid stenosis inevitably includes a neurological examination as well as CCT or MRI of the brain. Typical neurological and neuropsychological symptoms and signs as well as syndromes are described according to the vascular supply areas of the brain. CCT as well as MRI may identify cerebral infarction or other diseases and additionally give some information with regard to the underlying etiology or pathogenesis of an infarct. Satisfactory non-invasive demonstration of the carotid and vertebral arteries including their intracranial branches can be achieved by the use of sonographic methods (Dopplersonography, B-mode imaging, Duplex and colour-coded systems). Additionally, transcranial Dopplersonography is mandatory in most instances. Cerebral angiography is only justified preoperatively or for a disease which cannot be diagnosed reliably by other means, eg. cerebral venous thrombosis. The prognosis of a carotid stenosis depends not only on the degree of luminal narrowing and the shape of the stenosis but also on the clinical status of the patient (asymptomatic or symptomatic carotid stenosis, accompanying coronary artery disease etc.). Prophylactic treatment implies therapy of risk factors as well as antiaggregation, anticoagulation and carotid endarterectomy in selected cases. PMID- 1750159 TI - Neutrophil function in dogs with congenital ciliary dyskinesia. AB - In vitro neutrophil function was assessed in two English Springer Spaniel dogs, two Bichon Frise dogs, and one Chow Chow dog with congenital ciliary dyskinesia; three clinically normal English Springer Spaniel dogs that were presumed heterozygous for congenital ciliary dyskinesia; and five control dogs. Chemotaxis and random migration in affected and heterozygous dogs were found to be comparable to those of control dogs. Increased (P less than or equal to 0.05) neutrophil adhesion, antibody dependent cell-mediated cytotoxicity, iodination of proteins, and oxygen radical production in neutrophils from affected dogs were probably the result of chronic bacterial infection in vivo. Bacterial ingestion by neutrophils from the three heterozygous English Springer Spaniel dogs was significantly increased compared to control dogs but was not different from affected English Springer Spaniel dogs, suggesting a breed-related phenomenon. Significant decreases in neutrophil function were not seen in any of the dogs with congenital ciliary dyskinesia, indicating that a defective microtubular system is not shared by respiratory cilia and neutrophils and that defective neutrophil function does not contribute to respiratory infection. PMID- 1750160 TI - Ganglioneuromas of the thyroid gland in a colony of Sprague-Dawley rats. AB - Ganglioneuromas of the thyroid gland of Sprague-Dawley rats were found in 7.2% of 698 rats used in two, 2-year oncogenicity bioassays. The incidence of the tumor was unrelated to treatment or sex. Of the 52 ganglioneuromas of the thyroid gland identified in 50 animals, 40 (80%) had coincident C cell proliferations in the same or contralateral lobe. Ganglioneuromas were contiguous or commingled with C cell proliferations in 63.5% of the cases. The ganglioneuromas consisted of large ganglion cells and, in a few cases, cells thought to be less differentiated neuronal precursors, in a matrix of neurites and Schwann cells. They grew, infiltrating and expanding in the thyroid parenchyma, and did not metastasize. Immunohistochemical staining for calcitonin, S-100 protein, and neurofilaments, as well as electron microscopy, were used to further characterize the tumors. The close association of ganglioneuromas with C cell tumors supports the theory of neural crest origin of C cells and provides a parallel to the association of ganglioneuromas and pheochromocytomas in the adrenal medulla. This is the first report of ganglioneuromas occurring in the thyroid gland or occurring as a common entity in any species. PMID- 1750161 TI - Congenital and acquired melanocytomas (benign melanomas) in eighteen young horses. AB - In a retrospective study, cutaneous melanocytic tumors from 18 horses, less than 2 years old, were examined histopathologically and clinical follow-up requested. Melanocytomas (benign melanomas) occurred in a variety of breeds and in horses of varied coat color. The age of the horses at the time of biopsy ranged from 3 weeks old to 2 years old. Four melanocytomas were congenital, 11 melanocytomas were acquired by 1 year of age, and three were acquired prior to 2 years of age. Of the 18 horses, five were male, and 13 were female. All tumors were solitary and located on the legs or trunk; none were in the perineal region. Ulceration of the overlying epidermis was common. Tumors were generally localized and were not encapsulated. The tumors had a variety of cell patterns ranging from sheets, to streams, or nests of melanocytes. Cellular morphologic findings also ranged from epithelioid, to a mixture of epithelioid and spindle cells or to a spindle pattern. The nuclei were large and euchromatic, especially in the epithelioid cells. Several tumors had moderate cellular pleomorphism and binucleate cells. Mitotic activity was generally low (less than 1/high-powered field), but was readily detected (1-2/high-powered field) in bleached sections of four cases. Melanin pigmentation varied from mild to heavy. Melanophages were admixed with the tumor cells or in the adjacent tissue. Follow-up information was obtained on 15/18 horses and revealed that 14/15 horses were free of recurrence following excision. One neoplasm, that was poorly demarcated and had a spindle cell pattern, was not completely resected and continued to grow. These melanocytic tumors in young horses are distinct from melanomas in aged horses in their location, epithelial involvement, and age of horses affected. The majority of these tumors appear to be benign and share features of melanocytic nevi of human beings. PMID- 1750162 TI - Immunocytochemistry of canine thyroid tumors. AB - Immunocytochemical studies using the peroxidase-antiperoxidase method with commercial antibodies against thyroglobulin, calcitonin, calcitonin gene-related peptide (CGRP), neuron specific enolase (NSE), somatostatin, and neurotensin were performed on 38 Bouin-fixed, paraffin-embedded canine thyroid tumors obtained from necropsy and surgical files from 2 Ecoles Nationales Veterinaires (Alfort and Nantes, France) and from the Laboratoire d'Histo-Cytopathologie Veterinaire, Maisons-Alfort (France). The tumors consisted of two follicular adenomas, nine follicular carcinomas, nine solid carcinomas, 12 follicular-compact-cellular carcinomas, and six C-cell carcinomas. All 32 follicular-cell tumors were stained positively for thyroglobulin, half of them had weak to moderate positive immunoreactivity for NSE, and all histologic patterns were represented. They had no immunoreactivity for somatostatin or neurotensin. Four C-cell carcinomas had a solid alveolar pattern, while two had a pseudo follicular pattern characterized by uneven, often coalescent, pseudo-follicular formations with a multilayered epithelium surrounding a cavity that often contained red blood cells. Four C-cell carcinomas had uneven immunoreactivity for calcitonin, while all six were positive for CGRP or NSE. Immunoreactivity for CGRP was stronger or more widespread than positivity for calcitonin when both occurred in the same tumor. Some cells of three C-cell carcinomas had positive immunoreactivity for somatostatin. No immunoreactivity for neurotensin was detected. Seven tumors of follicular cell origin contained a few cells positive for calcitonin or CGRP, while three C-cell carcinomas had a few cells positive for thyroglobulin. These tumors were considered to contain entrapped remnants of normal thyroid tissue rather than being dual hormone producing tumors. PMID- 1750163 TI - Spontaneous fibro-osseous proliferative lesions in the sternums and femurs of B6C3F1 mice. AB - Bone morphology associated with fibro-osseous proliferation in the femurs and sternums of 98 female B6C3F1 mice were compared morphologically and quantitatively to femurs and sternums from 100 male B6C3F1 and 79 CF1 mice (48 female and 31 male). In addition, sternal samples from five B6C3F1 mice per sex were collected and processed for electron microscopy. Fibro-osseous proliferation was present in female B6C3F1 mice, but not male B6C3F1 or female CF1 mice. In female B6C3F1 mice at 32 weeks of age, the marrow spaces in the region of the proximal and distal epiphyseal plate were lined by large osteoblasts and had large vascularized centers. At 58 weeks, metaphyseal fibrovascular proliferative areas containing multinucleated cells and new cancellous bone delineating the lesion were seen. At 84 weeks, fibro-osseous tissue occupied the outer third of the sternal marrow cavity and by 110 weeks, more than two thirds of the marrow cavity. Fibro-osseous proliferation was present in 100 and 94% of the examined sternums and femurs, respectively, of female B6C3F1 mice at 110 weeks of age, but not in male B6C3F1 or female CF1 mice. Ultrastructural examination of the sternal changes at 110 weeks showed numerous osteoblasts, irregular bony spicules, and fibrocyte-like cells. By morphometry, the normal marrow cavity in B6C3F1 females occupied 35% of a longitudinal section of the whole sternebra compared with 70% and 75% of the whole sternebra in B6C3F1 males and CF1 female, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750164 TI - Cutaneous neoplasia in 340 cats. AB - A total of 340 cases of cutaneous neoplasia were diagnosed in 340 of 3,564 cats that were examined by biopsy or necropsy during a 41-month period from January 1, 1986 through May 31, 1989. Eighteen types of tumor occurred, but four types comprised 77% of the cases. These were basal cell tumor, 89 cases (26%, mean age 10.3); mast cell tumor, 72 cases (21%, mean age 8.6); squamous cell carcinoma, 52 cases (15%, mean age 11.6); and fibrosarcoma, 50 cases (15%, mean age 10.2). For each of these four types of tumors, peak number of cases occurred in cats older than 10 years. Mast cell tumor was the only tumor diagnosed in cats younger than 1 year. The head was the most common site for basal cell tumors, mast cell tumors, and squamous cell carcinomas. The legs were the most common location of fibrosarcomas. Siamese cats had approximately three times as many mast cell tumors as statistically expected, but only one-fourth as many squamous cell carcinomas. Breed predilection for other skin tumors was not apparent. Sex predilection was not detected for any skin tumor. PMID- 1750165 TI - Distinctive unclassified mesenchymal tumor of the digit of dogs. AB - Four examples of a mesenchymal tumor of undetermined histogenesis occurred in three mixed-breed dogs and one Yorkshire terrier. All tumors occurred as solitary, soft to firm, solid, tan, and ulcerated masses in the digits of dogs aged 11 to 15 years. The compact cellular tumor had cells with anisokaryotic round, oval, or irregular nuclei, some of which were multinucleated. The neoplastic cells appeared to arise in the tissue near the third phalanx in the area of dense collagenous trabeculae located proximal to the fat pad and sweat glands. The unclassifiable cells had some features of histiocytes by transmission electron microscopy, but failed to stain for lysozyme and alpha-1 antichymotrypsin, markers for monocyte-macrophage derived cells. Immunohistochemically, the cells stained for vimentin but not for cytokeratins, desmin, S-100 protein, epithelial membrane antigen, alpha-lactalbumin, lysozyme, alpha-1-antichymotrypsin, alpha-lactalbumin, casein, and heavy and light chain immunoglobulins. The combined findings of light and transmission electron microscopy and immunohistochemistry exclude tumor histogenesis from an epithelial cell, melanocyte, mast cell, plasma cell, Schwann cells, and Merkel cell. PMID- 1750166 TI - Spontaneous amelanotic melanomas of the uveal tract in F344 rats. AB - Five intraocular amelanotic melanomas were identified in the National Toxicology Program's database consisting of records from more than 60,000 female and 60,000 male F344 rats, which were used as control and treated animals in 2-year carcinogenicity studies. The five spontaneous melanomas were grossly observed as white or yellow, unilateral nodules, which originated in the region of the iris and ciliary body, often also involving the choroid. These amelanotic melanomas were composed predominantly of spindle cells arranged in a whorled pattern often with perivascular orientation. Mitotic figures were common in five tumors. The spindle cells had a positive immunoreactivity for S-100 protein but were negative for desmin. Electron microscopic studies provided clear evidence that these tumors originated from the uveal melanocytes. Ultrastructurally, the spindle cells contained numerous cytoplasmic premelanosomes (stage II melanosomes) that were not associated with melanin. Special histochemical studies showed that the spindle cells had a negative reaction for melanin. Although electron microscopic features are critical in the diagnosis of amelanotic melanomas of the uveal tract, the whorled pattern of spindle cells is a useful histologic criterion in differential diagnosis of this tumor in F344 rats. PMID- 1750167 TI - Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters. AB - The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice (n = 24, 6 to 8 weeks old) and hamsters (n = 9, 90-110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extraneural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extraneural disease before major central nervous system disease developed. PMID- 1750168 TI - Heterophil function in healthy chickens and in chickens with experimentally induced staphylococcal tenosynovitis. AB - Heterophil function was evaluated in 16 healthy chickens and in 46 chickens with experimentally induced staphylococcal tenosynovitis. In paired blood samples, heterophils from chickens with tenosynovitis had a significant increase in adherence, chemotaxis, phagocytosis, and bacterial killing of Staphylococcus aureus compared to heterophils from healthy chickens. The percent adherence of heterophils to nylon fiber columns increased significantly from a 78.4% mean +/- 6.6% standard deviation to 87.6% +/- 3.2% after induction of staphylococcal tenosynovitis. Heterophil movement following in vitro exposure to saline or endotoxin was increased in chickens with tenosynovitis; 3 +/- 1 heterophils/0.25 mm2 to 10 +/- 6 heterophils/0.25 mm2 and 136 +/- 29 heterophils/0.25 mm2 to 340 +/- 74 heterophils/0.25 mm2, respectively. Endotoxin-activated serum was chemoattractive for heterophils from all chickens. Flow cytometry was used to define the heterophil population on light scatter histograms, evaluate individual cell phagocytosis of latex beads, and quantitate the number of beads phagocytosed per heterophil. When incubated with increased numbers of beads, only heterophils from chickens with tenosynovitis phagocytosed higher numbers of beads. At heterophil to bead ratios of 1:10, the percentage of heterophils that phagocytosed beads increased from baseline values of 37.8% +/- 9.0% to post infection values of 67.3% +/- 7.5%. Using 1:20 heterophil to bead ratios, heterophil phagocytosis increased from 38.7% +/- 9.9% to post-infection values of 79.8% +/- 7.3%. Heterophils from all chickens were able to phagocytose and kill log phase staphylococcal bacteria. After phagocytosis, the heterophils from chickens with staphylococcal tenosynovitis rapidly decreased the number of viable bacterial colony forming-units per milliliter by approximately one log.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750169 TI - Bovine undifferentiated alveolar rhabdomyosarcoma and its differentiation in xenotransplanted tumors. AB - At necropsy, a 7-year-old Holstein cow, clinically diagnosed via rectal palpation as having malignant abdominal neoplasia was found to have many metastatic tumors of various sizes in the abdominal and thoracic cavities and in the liver, lung, kidney, adrenal, uterus, and lymph nodes. These tumors were examined by histologic and immunohistochemical methods using anti-human myoglobin, anti bovine myoglobin, and anti-desmin sera. Tumors were diagnosed as undifferentiated alveolar rhabdomyosarcomas. The tumors in the abdominal and thoracic cavities differed histologically from the metastases in organs. The former tumors consisted of only undifferentiated cells, most of which did not stain positively for desmin or myoglobin. The metastatic tumors contained a few rhabdomyoblastic cells that stained positively for desmin and myoglobin. Tumors tissues from the cow were transplanted and propagated through six passages in athymic nude mice. After one passage, the transplanted tumor histologically resembled those from the abdominal serosa and consisted of cells with scanty cytoplasm with an alveolar arrangement. Cells from this tumor stained positively for desmin and negatively for myoglobin. After two passages through nude mice, tumor cells were of two distinct histologic types: those cells with scanty cytoplasm and elongated cells with plentiful eosinophilic cytoplasm. Both of these cells stained positively for both desmin and myoglobin. After six passages, cross striations were detected in neoplastic cells by electron microscopy. These findings illustrate that a highly undifferentiated bovine rhabdomyosarcoma, in which most of the cells in the original tumor lacked desmin and myoglobin, became better differentiated and stained positively for desmin and myoglobin after serial transplantation in nude mice. PMID- 1750170 TI - Intradermal neutrophil mobilization induced by complement fragments and endotoxin is more effective in neonatal than in adult cattle. PMID- 1750171 TI - Prevalence and location of mast cell tumors in slaughter cattle. PMID- 1750172 TI - Dentigerous cysts in sheep. PMID- 1750173 TI - Transmission of salmonellae among calves penned individually. AB - An analysis of the spatial and temporal patterns of excretion of salmonellae by calves penned individually showed that non-contagious routes were more important than contagious routes in disease spread. The avoidance of aerosol production, and the effective cleaning and disinfection of utensils between feeds and of buildings between batches, are likely to be more important than pen design in the control and prevention of calf salmonellosis. PMID- 1750174 TI - Physiological responses of sheep to two hours anaesthesia with diazepam-ketamine. AB - The cardiopulmonary effects of repeated intravenous injections of a combination of diazepam and ketamine for anaesthesia were evaluated in six domestic sheep. Induction doses of 0.375 mg/kg and 7.5 mg/kg were followed by maintenance doses of 0.188 mg/kg and 3.75 mg/kg every 15 minutes for 105 minutes. Although this dosing regimen produced the desired anaesthetic effects, it caused untoward cardiopulmonary effects. Salient features of multiple dosing with diazepam and ketamine were hypoventilation, respiratory acidosis and an increase in both systemic and pulmonary vascular resistance. PMID- 1750175 TI - Immobilisation of southern elephant seals and leopard seals with cyclohexamine anaesthetics and xylazine. AB - Ketamine and xylazine were given to 55 southern elephant seals (Mirounga leonina) for stomach lavaging, and to three leopard seals (Hydrurga leptonyx). The elephant seals showed prolonged apnoea and two of them died owing to aspiration of stomach contents. Two of the leopard seals died from unknown causes. Tiletamine and zolazepam were given to five elephant seals and one leopard seal. Two of the elephant seals and the leopard seal died from unknown causes. Xylazine alone was administered to 34 leopard seals. Sedation was poor at low dose rates (less than 1.7 mg/kg) but four of the seals given higher dose rates died owing to the aspiration of stomach contents. PMID- 1750176 TI - Cryptosporidiosis in game birds. PMID- 1750177 TI - Patent urachus with a perforated urethra in a Nigerian Balami lamb. PMID- 1750178 TI - Use of transtracheal aspiration to identify pathogens in pneumonic calves. PMID- 1750179 TI - Anticoccidial efficacy of diclazuril in partridges. PMID- 1750180 TI - Homeopathic remedies. PMID- 1750181 TI - Homeopathic treatment of a dog. PMID- 1750182 TI - Systolic cardiac murmurs in boxers. PMID- 1750183 TI - Enterotoxaemia in cats. PMID- 1750184 TI - Practice in Bulgaria. PMID- 1750185 TI - Pathology of septum formation in primary biliary cirrhosis: a histological study in the non-cirrhotic stage. AB - Bridging or incomplete septum formation, an important step leading to cirrhosis in various chronic progressive liver diseases, was examined in 231 liver biopsy specimens of primary biliary cirrhosis (non-cirrhotic stage. Incomplete septa from the enlarged portal tracts and portal to portal bridges were frequent and appeared first, while portal to central ones appeared subsequently and became frequent in the liver specimens with changes resembling cirrhosis. These septa were divided into four types histologically: ductular, lymphocytic, loose connective tissue and fibrous type. More than one type was usually found in the same specimen. The pathology of the first three types was similar to and frequently continuous with that of neighbouring periportal regions, suggesting that most of these septa were formed by the extension of periportal destructive processes. The fibrous type might be an advanced form of the other three types. Incomplete septa seemed to pinch off part of the hepatic parenchyma in a hepatic lobule; this was followed by an unusual enlargement of the portal tracts and an approximation of portal tracts and central veins. There were perivenular hepatocellular necroses on occasion. Progression of periportal hepatocellular damage may lead to septum formation and finally progress to cirrhosis, in primary biliary cirrhosis. The significance of perivenular necroses remains speculative. PMID- 1750186 TI - Purkinje cell toxicity of beta-aminopropionitrile in the rat. AB - Compounds causing neurolathyrism are putative aetiological agents in neurodegenerative disorders including amyotrophic lateral sclerosis. beta Aminopropionitrile (BAPN) is one such compound. We have administered this lathyrogenic agent at a dose of 1 g/kg by the intraperitoneal route in experiments in adult Sprague-Dawley rats during a period of 10 weeks. The rats developed marked kyphoscoliosis, ataxia with paralysis and muscle wasting of the hind limbs. Vacuolation and loss of Purkinje cells developed, but no anterior horn cell degeneration was noted. Immunohistochemical studies of phosphorylated neurofilaments and the 72 kDa heat shock protein were normal and no intraneuronal ubiquitinated inclusions were seen. High-dose intraperitoneal BAPN in the rat causes Purkinje cell changes, but no other central nervous system abnormalities. PMID- 1750187 TI - The histopathology of the liver in older patients with hepatitis B virus surface antigenaemia. AB - The histopathology of the liver and the detectability of intrahepatic hepatitis B virus (HBV) markers were studied in 34 autopsy cases in elderly patients (mean age 73.9 years, range 60-91 years) who had had a history of positive HBV surface antigenaemia prior to death. Seven of 14 persistent HBV carrier cases (group A) in which long-lasting HBV surface antigen (HBsAg) carriage in the sera had been confirmed by sequential assays, and 5 out of 15 HBV-infected people (group C, single assay) showed significant primary liver damages including chronic hepatitis, toxic hepatitis, liver cirrhosis and hepatocellular carcinoma. In 5 cases (group B), one of which was type B liver cirrhosis, HBsAg became negative and HBsAb appeared during the follow-up period (up to 33 months). Among confirmed HBV carriers, HBsAg and HBV core antigen were most frequently found in the liver of cirrhotic cases with and without hepatocellular carcinoma (5 of 6), whereas these were rarely detected in those with non-specific changes or slight hepatitic activity (1 of 7). All 5 cases in group B were negative for histological HBV related antigens and the findings in group C were variously interpreted. Post mortem cases of the aged HBV carriers who survived their mean life expectancy represent an important population in which to study the natural history of HBV carriers. PMID- 1750188 TI - Endosteal surfaces in hyperparathyroidism: an enzyme cytochemical study on low temperature-processed, glycol-methacrylate-embedded bone biopsies. AB - Alkaline phosphatase (AlP) and tartrate-resistant acid phosphatase (TRAP) activities have been studied comparatively in needle biopsies of the iliac crest of four cases of secondary hyperparathyroidism (renal osteodystrophy). AlP activity was associated with the plasma membrane of osteoblasts and their processes, of reticular cells of bone marrow and of young osteocytes of osteoid borders and woven bone. Moreover, it was detected in the fibroblast-like cells of the endosteal "fibrosis". These cells were orderly in arrangement and were parallel to the endosteal surfaces near zones of bone formation. They were disorderly near zones of bone resorption. A strong TRAP-positive reaction was present in osteoclasts and mononuclear cells of endosteal "fibrosis" and in osteocytes located near active osteoclasts and in woven bone. These results suggest that the so-called fibrosis of hyperparathyroidism, rather than representing reparative, inert tissue, consists of osteoblast-like cells, probably precursors of osteoblasts derived by parathormone-stimulated proliferation of AlP-positive stromal cells of bone marrow, and of TRAP-positive, mononuclear cells, probably preosteoclasts. Moreover, they show that TRAP activity can be present in osteocytes, probably under stimulation by the same factors which stimulate osteoclast activity. The histochemical demonstration of AlP and TRAP facilitates the morphological diagnosis of metabolic bone disease and may improve knowledge of bone physiopathology. PMID- 1750189 TI - Morphological and cytogenetic studies of angiosarcoma in Stewart-Treves syndrome. AB - A morphological and cytogenetic analysis of a multifocal angiosarcoma in a typical case of Stewart-Treves syndrome is reported. The morphological analysis indicated differentiation along both blood and lymph vessel endothelium lines. By light and electron microscopy there were areas with well-developed erythrocyte containing, capillary-like vessels and poorly differentiated areas with abortive vascular formations. In these the endothelium revealed immunoreactivity to factor VIII RAg, binding of Ulex europaeus I and Psophocarpus tetragonolobus agglutinin lectins, Weibel-Palade bodies ultrastructurally and presented a continuous enclosing external lamina and immunoreactivity for laminin and collagen IV, all features of blood-vessel differentiation. There were also lymphangioma-like areas as well as poorly differentiated areas where the immunohistochemical, lectin binding and ultrastructural features were compatible with a lymph vessel differentiation. Cytogenetic analysis of cultured tumour cells revealed chromosome counts in the diploid region. About 40% of the cells analysed had a normal diploid karyotype. The remaining cells showed a multitude of mainly nonclonal structural alterations; 17 unique marker types resulting from different translocations and deletions were observed. There were also a few cells with clonal numerical deviations showing monosomy 22, monosomy X and trisomy 2 respectively. It is of interest that the losses of chromosome 22 and the X chromosome also have been observed in Kaposi's sarcoma and that the PD-ECGF gene, a novel angiogenetic factor, has been mapped to chromosome 22. PMID- 1750190 TI - Leu-M 1 immunoreactivity in papillary carcinomas of the thyroid gland; microcarcinoma, encapsulated, conventional and diffuse sclerosing subtypes. PMID- 1750191 TI - A study of malignant lymphomas in Iran, based on the updated Kiel classification. AB - One hundred and sixty-two consecutive cases of malignant lymphomas were collected from two diagnostic centres in north and south Iran. Tissue samples were examined by immunohistological methods, and the non-Hodgkin's lymphomas were classified according to the updated Kiel classification. The distribution of the different types of malignant lymphoma in this study is compared with the situation in Western countries. PMID- 1750192 TI - Paragangliomas: neuroendocrine features and cytometric DNA distribution patterns. A clinico-pathological study of 22 cases. AB - Paragangliomas from 22 patients with extraadrenal tumours of this type were studied. Neuroendocrine features were examined using immunohistochemical techniques. Twenty-two antisera raised against neuroendocrine "markers", regulatory peptides, serotonin and intermediate filament proteins were studied in this group and cytometric DNA assessments were made by means of image cytometry. One normal and 5 hyperplastic carotid bodies were used as controls in the DNA cytometric investigations. Clinical and/or histopathological evidence of "malignancy" was present in 5 cases. The tumour cells showed heterogeneity with regard to their expression of different peptides, and the immunohistochemical analyses did not permit differentiation between benign and malignant paragangliomas. An euploid nuclear DNA distribution pattern was found in all controls and in 17 of the tumours; all except 1 were clinico-pathologically benign. An aneuploid DNA pattern was observed in 5 of the cases and some malignant features were present in 4 of these cases. DNA data may give further information apart from that obtained from the histopathological findings which may be of value in predicting the biological behaviour of this tumour type. PMID- 1750193 TI - Nuclear DNA content in 27 pancreatic endocrine tumours: correlation with malignancy, survival and expression of glycoprotein hormone alpha chain. AB - Paraffin-embedded tissue from resection specimens of 14 functioning and 13 nonfunctioning pancreatic endocrine tumours (PET) was analysed for nuclear DNA content by image cytometry. Data on follow-up (mean 5.5 years) were available in all patients. DNA histograms with a diploid pattern were found in 13 (48%) tumours, while an aneuploid pattern was seen in the remaining 14 tumours (52%). Six (40%) of the diploid tumours and 9 (60%) of the aneuploid tumours were malignant. Survival was shorter in patients with malignant and aneuploid PET (mean 3.5 years, range 0.5-7) than in those with malignant and diploid PET (mean 5.7 years, range 3-8). Human chorionic gonadotropin-alpha was expressed in 3 of 12 benign PET, with 1 being aneuploid, and 6 of 15 malignant PET, with 4 being aneuploid. We conclude from these results that the ploidy pattern of PET allows no discrimination between benign and malignant tumours but may provide prognostic information on the aggressiveness of malignant PET. PMID- 1750194 TI - Is the grading of breast carcinomas affected by a delay in fixation? AB - The effect of delay in fixation on the modified Bloom and Richardson grade of eight breast carcinomas was investigated. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 2, 4, 6, 18 and 24 h after surgical removal. The grade of each tumour was assessed at delays of 0.5 and 6 h. The tubule formation and nuclear pleomorphism components of the grade showed no change with a delay in fixation of 6 h. The number of mitotic figures declined by a mean of 53% over the same period and this resulted in a decrease in the histological grade of one of the tumours. The implications of these findings for the handling of breast specimens in a diagnostic histopathological laboratory are discussed. PMID- 1750195 TI - Mucin-histochemical and immunohistochemical profiles of epithelial cells of several types of hepatic cysts. AB - Epithelial cells of several types of hepatic cysts were examined by mucin histochemistry and immunohistochemically. There were some differences in mucus and antigenic expression among the hepatic cysts examined. Epithelial cells of non-parasitic simple cysts and adult-type polycystic liver showed similar mucin histochemical and immunohistochemical features, and were characterized by little mucin and weak immunoreactivities to several antibodies examined. Epithelial cells of hepatic hilar cysts were characterized by much mucin and moderate immunoreactivities to carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Epithelial cells of ciliated hepatic foregut cysts were characterized by much mucin and immunoreactivities to actin and tubulin which were positive in cilia. Epithelial cells of biliary cystadenoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. Epithelial cells of biliary cyst-adenocarcinoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. These differences in epithelial mucus and antigenic expression among several types of hepatic cysts may reflect differences in their origin and biological characteristics. These differences may be helpful in the differential diagnosis of hepatic cysts in small biopsy specimens. PMID- 1750196 TI - Quantitative analysis of nucleolar margination in diagnostic cytopathology. AB - The diagnostic value of nucleolar margination, defined as the percentage of nucleoli touching the nuclear membrane, was investigated in 359 cytological preparations of benign and malignant lesions of the thyroid, breast, prostate and central nervous system. Premalignant lesions of the uterine cervix and non invasive papillary carcinomas of the bladder were also examined. It was observed that the percentages in benign lesions were, in general, lower than in the malignant and that the values increased progressively with increasing grade in the cervix and bladder. When the overlap index was calculated, this gave exact information on the usefulness of nucleolar margination in distinguishing benign from malignant lesions, particularly in the prostate and thyroid and, to a lesser extent, in the breast and central nervous system. As for lesions of different grades, the calculation of the index allowed the identification of two subgroups, one corresponding to low grades (mild cervical dysplasia or urothelial papillary carcinoma of grade 1), the other subgroup to high grades (severe cervical dysplasia and carcinoma in situ, or papillary carcinoma of grade 3). Moderate dysplasia cases and grade 2 papillary carcinomas do not appear as separate intermediate categories but rather show values falling into the range of either the higher or lower grades. The margination values obtained from the cytological preparations corresponded well to those in the histological slides obtained from the resected specimens. In conclusion, nucleolar margination appears to be a feature which is easy to evaluate in a reproducible way and useful in cytological diagnosis. PMID- 1750197 TI - Very large peroxisomes in distinct peroxisomal disorders (rhizomelic chondrodysplasia punctata and acyl-CoA oxidase deficiency): novel data. AB - We report very large hepatic peroxisomes (d-circle greater than 1 micron) in a patient with rhizomelic chondrodysplasia punctata and a patient with acyl-CoA oxidase deficiency. The effects of peroxisomal enlargement on the enzymatic activity are discussed. As increase in peroxisomal size is also reported in at least 12 other patients with peroxisomal disorders, we propose a relationship between the enlargement of the organelles and their functional deficiency. PMID- 1750198 TI - [Kidney sorbitol dehydrogenase: kinetic mechanism]. AB - Properties of sorbitol dehydrogenase isolated from rat kidney were studied. Sorbitol dehydrogenase reactions followed the consecutive irregular order as shown in studies of kinetic patterns, inhibition by end products and thermoinactivation of the enzyme in the presence of substrates. PMID- 1750199 TI - [Protein metabolism in patients with atherosclerosis using a 15(N) isotope]. AB - Incorporation of 15N into blood plasma proteins and blood cells was studied in 11 patients with ischemic heart disease and peripheric atherosclerosis and in 7 healthy volunteers after oral administration of 15NH4Cl (95 atm%/15N) at a dose of 3 g per 70 kg of body mass. Metabolism of fibrinogen was stimulated, while incorporation of 15N into thrombocyte proteins was decreased in the patients with atherosclerosis as compared with healthy persons. Possible reasons of these alterations are discussed. PMID- 1750200 TI - [Various features of the formation and secretion of bile acids in spontaneous atherosclerosis]. AB - Main pathways of cholesterol catabolism were found to be dissimilar in patients with spontaneous coronary atherosclerosis accompanied by hyperlipoproteinemia as compared with healthy persons of the same age. In the patients, independently of the hyperlipoproteinemia type, a longer pathway prevailed which terminated at the step of cholic acid formation, while in healthy persons the shorter pathway was found to be discontinuous after chenodeoxycholic acid production. The specific property of cholesterol catabolism in healthy persons appears to be due to a decrease in activity of V12 alpha-hydroxylase thus protecting against development of spontaneous atherosclerosis. PMID- 1750201 TI - [Stability of serum immunoglobulin conformation in various tumors]. AB - As shown by means of temperature-perturbation differential spectrophotometry blood serum immunoglobulins G from patients with gastric cancer and with some other tumors were more resistant to 2 M urea as compared with the immunoglobulins from healthy volunteers and patients with gastric ulcerous disease. The resistance of IgG conformation was altered in the course of gastric cancer treatment. PMID- 1750202 TI - [Characteristics of the structure and biological role of lysophospholipids]. PMID- 1750203 TI - [Proteolytic lysosomal enzymes in ovarian cancer]. AB - Activity of lysosomal proteinases cathepsins B and D was studied in normal tissues, malignant and benign ovary tumors, in blood sera and ascites fluid of patients with primary ovary cancer. The cathepsin B activity was 12-fold higher in tissues of ovary malignant tumors as compared with that of normal ovary and 6 fold higher -- as compared with tissues of benign tumors. Activation of the enzyme depended directly on the mass of malignant tumors and on the intensity of their penetration into surrounding tissues (uterus, urinary bladder, small pelvic fat) and spreading over peritoneum. Activity of cathepsin D was 2- and 2.6-fold higher in malignant ovary tumors as compared with normal tissue and benign tumors, respectively. The data obtained suggest that estimation of cathepsins B and D activities in bioptic material from ovary tumors might be useful for diagnosis of the disease. PMID- 1750204 TI - [Comparative characteristics of membrane bound and cytoplasmic monoamine oxidases in human placenta]. AB - Catalytic and physico-chemical properties of human placental monoamine oxidases (MAO) were studied. Both forms of the enzyme, membrane-bound and soluble, exhibited similar properties: optimal activity at pH8.3, equal rate of inhibition with selective MAO inhibitors, identical substrate specificity (the best substrate--serotonin). Some specific differences were found only for cytoplasmic (soluble) MAO: lower affinity for substrates as compared with membrane-bound enzymes, reversible interaction with an inhibitor Lilly 51641 even after long term preincubation, whereas the mitochondrial MAO bound Lilly 51641 irreversibly. The property of cytoplasmic MAO to form aggregates during storage and/or in gel filtration and concentration did not affect the main catalytic properties of soluble enzyme. Analysis of isoenzyme spectra of membrane-bound and cytoplasmic MAO by means of selective inhibitors and electrophoresis showed that MAO of the two types--A and B were detected in all the subcellular fractions studied. Subunits of MAO of the A type had molecular masses 62, 61 and 61 kDa and of MAO of the B type--51, 55 and 55 kDa in mitochondria, microsomes and cytosol, respectively. PMID- 1750205 TI - [Brain monoamine oxidase during aging]. AB - MAO activities were studied in 4 months old and 19 months old Wistar rats. MAO-B activity was higher in brain stem and hemispheres of old rats as compared with that of young animals. MAO-A activity was lowered only in the stem and was not changed in the hemispheres of old rats. Actinomycin D increased MAO-A activity in the brain stem of young rats and lowered MAO-B activity in the hemispheres of old rats. Emotional stress increased MAO-A activity in the stem and hemispheres of both young and old animals. Actinomycin D abolished the stress effect on these two forms of MAO both young and old rats. Delta-sleep including peptide at the dose of 120 micrograms/100 g increased MAO-A activity and lowered MAO-B activity in young animals but did not affect the MAO-A activity in old rats. PMID- 1750206 TI - [Regulation of the activity of brain cytoplasmic creatine kinase by pyridine nucleotides]. AB - Effect of oxidized and reduced forms of pyridine nucleotides on activity of creatine kinase BB was studied in rat brain. NAD did not affect the enzymatic activity at concentrations of 1.0-4.0 mM, while in presence of NADH activity of creatine kinase BB was gradually decreased as the coenzyme concentration increased. The plot of 1/V against 1/S at various NADH concentrations produced a series of lines intersecting at one point (-1/Km), thus indicating the noncompetitive type of brain cytoplasmic creatine kinase inhibition by reduced pyridine nucleotides. Apparent Ki value for NADH was about 1.5 mM which was lower than the known parameter for cytoplasmic creatine kinase isozymes from skeletal and heart muscles. Dependence of brain creatine kinase BB on the rate of pyridine nucleotide reduction suggested a possible mechanism for the enzyme regulation under hypoxic conditions. PMID- 1750207 TI - [The effect of early visual deprivation on the level of N-acetyl-1-asparaginic acid and the activity of phosphate-activated glutaminase in visual analyzer structures and various regions of the dog cerebral cortex and cerebellum]. AB - Under conditions of 45-days visual deprivation content of N-acetyl-L-aspartic acid was considerably increased in visual cortex (field 17) tissues and decreased in the superior colliculus and exterior geniculate body. At the same time, content of N-acetyl-L-aspartic acid was not altered in the visual cortex mitochondrial fraction; in the outer structures studied level of this amino acid was distinctly decreased both in tissues and mitochondrial fractions. After prolongation of the visual deprivation up to 90 days content of N-acetyl-L aspartic acid was sharply decreased in tissues and mitochondrial fractions of all the formations studied of dog brain visual analyzer. The maximal 4.5-fold decrease was found in mitochondrial fractions of the visual analyzer (field 17), in the exterior geniculate body and superior colliculus content of the amino acid was decreased 2.4-3.9-fold as compared with controls. In 90 days-long visual deprivation total activity of phosphate-dependent glutaminase was considerably increased (1.18-3.71-fold as compared with controls) in myelinic (A), membraneous (B), light (C), and heavy synaptosomal and synaptic mitochondrial (E) subfractions of the visual cortex (field 17). The rate of the enzyme activation was distinctly higher in these subfractions as compared with that of the motor and parietal cortical subfractions. After 90 days-long visual deprivation the similar alterations were found in A, B, D and E cerebellum subfractions but these alterations were less distinct as compared with the visual, motor and parietal subfractions. PMID- 1750208 TI - [Stable reduction of endogenous insulin production in the body in experimental insulin-dependent diabetes]. AB - Implantation of beta-cells allogenic culture into animals with alloxan diabetes did not produce persistent positive effect. The implanted beta-cells lost their viability as a result of toxic effect of natural diabetogenic factor occurring in blood plasma during insulin-dependent diabetes. Long-term administration of heparin into these animals within first 90 days of the experiment enabled to avoid the negative phenomenon and to neutralize the diabetogenic factor activity. Under these conditions the implanted beta-cells effectively produced endogenous insulin and the symptoms of diabetes disappeared within 14 months. PMID- 1750209 TI - [Pancreatic glycosaminoglycans in acute pancreatitis]. AB - Content of glycosaminoglycans was increased in pancreas of rats with acute pancreatitis. With development of the disease not only content of glycosaminoglycans but heterogeneity of their molecules were increased. This suggests that carbohydrate chains of glycosaminoglycans were degraded; the rate of degradation correlated with severity of pancreatitis. PMID- 1750210 TI - [Age-dependent status of the antioxidant system of rat tissues under the effect of short-term vibration]. AB - Oxidation of low molecular thiols and ascorbic acid, alterations in superoxide dismutase, catalase, glutathione reductase and glucose-6-phosphate dehydrogenase activities were observed in erythrocytes and tissues of rats after short-term total vertical vibration. The rate of alterations found depended on the initial state of the antioxidative system components as well as on the vibration duration. The most pronounced impairments of the antioxidative system were detected in blood and nervous system of old animals in which the initial level of the antioxidative system functional activity was minimal. PMID- 1750211 TI - [Regulation of by arginine of cytochrome p-450 activity and lipid peroxidation in rat liver and testicular tissue during hypoxia]. AB - Arginine, preadministered intraperitoneally at a dose of 120 mg per 100 g of body mass before hypoxia, decreased content of diene conjugates by 42-64% and Schiff bases by 7-15% in rat liver and testicular microsomal membranes as compared with control rats nontreated with arginine. Under these conditions cytochrome P-450 catalytic activity with aniline as a substrate was increased by 65-152% and with amidopyrine as a substrate--by 72-148%, respectively. Exogenous arginine inhibited an increase in membranes microviscosity, specific for hypoxic state; relative microviscosity of lipid bilayer was decreased by 36% and of the protein lipid contact zones--by 84% as compared with control hypoxic animals. PMID- 1750212 TI - [Efficacy of various antioxidants in experimental ischemia and myocardial infarct in the rat]. AB - Complex of vitamins E and C showed the most effective antinecrotic action in rats with simulated myocardial infarction in series of antioxidants studied: ascorbate, alpha-tocopherol, quercetine, derivatives of o-benzoquinone OBQ2 and OBQ3. Stabilization of lipid peroxidation in cardiomyocytes, increase in biomembranes stability and absence of distinct alterations in the antioxidative enzymatic system were found in rats with ischemia and myocardial infarction after treatment with the complex. Protective effect of the vitamins E and C complex was realised via antiradical mechanism. PMID- 1750213 TI - [Effect of the functional state of the central nervous system on brain lipid peroxidation processes in experimental cranial-brain trauma]. AB - Interrelationship between the functional state of central nervous system and brain metabolism was studied in animals with craniocerebral trauma. Stimulation of nervous activity was shown to prevent an increase in lipid peroxidation in brain of the experimental animals. A distinct decrease of the brain antioxidative activity was also noted. Lipid peroxidation and antioxidative activity were markedly impaired in the animals with craniocerebral trauma either after depression of central nervous system or without any additional treatment. PMID- 1750214 TI - [Metabolism of thiamine and its di- and triphosphorus esters in the blood of patients with neurological symptoms of osteochondrosis]. AB - Concentrations of phosphate esters in blood of patients with vertebral osteochondrosis and activities of enzymes involved in thiamine metabolism have been investigated. The pathological processes were characterized by a decrease in content of thiamine triphosphate while concentration of coenzyme, thiamine diphosphate, was relatively constant. The enzymes involved in the initial and final steps of biosynthesis and degradation of thiamine phosphorylated derivatives play the main role in maintaining vitamin B1 metabolic homeostasis. PMID- 1750215 TI - [Metabolic function of isolated liver mitochondria during various conditions of vitamin D and K supply and administration of pelentane]. AB - Alimentary deficiency of vitamin K caused a decrease in the rate of respiration in presence of ADP and in the rate of oxidative phosphorylation in the presence of succinate. Administration of the antivitamin K pelentane, excess of vikasol and deficiency of vitamin D did not affect these parameters. As distinct from controls and rats treated with pelentane, transport of calcium was decreased in presence of all the substrates studied in mitochondria isolated from liver tissue of animals deprived of vitamins K and D as well as of animals treated with vikasol excess. At the same time, accumulation of calcium led to time-dependent inhibition of respiratory chain if NAD-dependent substrates were used. Possible reasons of dissimilarity observed are discussed; the phenomenon found may occur due to exhaustion of the mitochondrial pyridine nucleotides pool. The data obtained suggest that antivitamins K altered only some parameters of body status (prothrombin time) similarly to the alterations observed in alimentary deficiency of vitamin K. PMID- 1750216 TI - [Level and ratio of prostaglandins group E and F2(alpha) in bronchoalveolar washes in pulmonary tuberculosis patients]. AB - Content of prostaglandins PGE and PGF2 alpha was studied by means of radioimmunoassay; their ratio was calculated in bronchoalveolar lavages obtained from impaired lung and from contralateral, intact lung of 86 patients with various forms of pulmonary tuberculosis. Concentration of prostaglandins was calculated per 1 mg of protein in lavage to standardize the data obtained. In the patients with tuberculosis production of PGE was increased in both lungs. However, the prostaglandin content was distinctly higher in the impaired lung but approximately similar in various forms of the disease. Hyperproduction of PGF2 alpha occurred in the impaired lung and depended on the type of the process. Content of PGF2 alpha was maximal in complicated destructive forms of tuberculosis. Bronchial muscle tension depended on the ratio of both groups of prostaglandins in bronchoalveolar space. Bronchial obstruction was accompanied by a decrease of PGE content in intact lung and by high concentration of PGF2 alpha near the tuberculosis focus. PMID- 1750217 TI - [Physico-chemical properties of alveolar surfactant in intermediate type allergy]. AB - Development of sensitization involved accumulation of protein, lipoproteins and neutral triglycerides in lung surfactant, which inactivated surface active phospholipids and decreased the surface activity of surfactant. In anaphylactic shock a decrease in content of phospholipids and alteration of their fatty acid spectrum occurred as a result of which the moistening capacity of the covering complex was lowered and expiration of the bronchoalveolar secretion was restricted thus contributing to formation of asphyxia. PMID- 1750218 TI - [Use of reagents from various firms in the "Spectrum" biochemical analyzer made by Abbott Laboratories]. PMID- 1750219 TI - [Enzymatic methods for quantitative determination of total cholesterol in blood serum]. AB - Advantages and disadvantages of enzymatic assays of total cholesterol content in human blood serum are reviewed. Factors, affecting these assays are discussed: specificity of the enzymes used (cholesterol esterase and cholesterol oxidase), conditions of analysis and composition of the reaction mixture, interference with components of blood serum. Adaptation of the enzymatic assays of total cholesterol estimation for various types of biochemical analyzers, including systems containing immobilized enzymes, is considered. PMID- 1750220 TI - [Spectrophotometric determination of lipid peroxidation end products]. AB - Spectrophotometric assay of the final lipoperoxidation products based upon light absorption at 400 nm was developed. Relative content of these products in different phases of lipid extract was calculated as E400/E220 ratio. Data obtained by the technique developed were consistent with those of histochemical results. Appreciable correlation between the relative lipoperoxidation products content and age was demonstrated. PMID- 1750221 TI - The present status of eicosanoids and related substances in the control of the cardiovascular system. PMID- 1750222 TI - [Metabolism of intravenously administered prostaglandin E1 in patients with peripheral arterial occlusive disease]. AB - Using high performance liquid chromatography and radioimmunoassay we have investigated the stability of prostaglandin (PG) E1 and its metabolite 13,14 dihydro-PGE1 in human plasma as well as the initial metabolism of PGE1 infused intravenously (80 micrograms/patient/hour) in patients with peripheral arterial occlusive disease. 13,14-dihydro-PGE1 degraded like PGE1 in human plasma at 37 degrees C with a half-life of several hours. During infusion of PGE1 higher plasma concentrations of the major metabolite 15-keto-13,14-dihydro-PGE1 and lower plasma levels of PGE1 and 13,14-dihydro-PGE1 were observed. The metabolite 13,14-dihydro-PGE1 is of interest, since in contrast to 15-keto-13,14-dihydro PGE1 it is biologically active. The biosynthesis of 13,14-dihydro-PGE1 could contribute to the therapeutic efficacy of PGE1 administered intravenously in patients with peripheral arterial occlusive disease. PMID- 1750223 TI - [Prostaglandin E1 in therapy of peripheral arterial occlusive disease]. AB - The intraarterial and intravenous infusion of prostaglandin E1 (PGE1) today is well established in the therapy of peripheral arterial occlusive disease. This review summarizes the results of pharmacological-clinical studies and the influence of PGE1 on the pathomechanism of ischaemia due to its antithrombotic, leukocyte and endothelial stabilizing properties. Clinical data available on continuous and intermittent infusion for both modes of administration are critically appraised, taking into account more recent data on active metabolites. PMID- 1750224 TI - [Risk factors of atherosclerosis: results of screening in Southern Austria]. AB - In the western industrialized countries atherosclerosis is the leading cause of death. In this investigation serum cholesterol and blood pressure were measured in 4321 (60.9% females) inhabitants of Lower Austria. In addition, a short cardiovascular history was taken and age, sex, body weight, height and smoking habits were recorded. In the various villages the mean serum cholesterol differed considerably (194 +/- 52-244 +/- 49 mg/dl). Overall, women had a slightly, but non-significantly, higher serum cholesterol (224.0 +/- 53.5 mg/dl) than men (218.6 +/- 58.4 mg/dl). Although 2/3 of the participants showed an elevated serum cholesterol, only 6% were taking lipid lowering drugs. An age-dependent increase in cholesterol was found in women, whereas this correlation was present in men only until the age of 40. Approximately 30% of the participants reported a positive family history. A comparison with the mortality register showed a correlation between smoking and bronchogenic cancer. No correlation, however, was demonstrable between smoking and cardiovascular mortality--perhaps due to methodological difficulties. Regional analysis of the results indicates the importance of the role of local general practitioners in the prevention of atherosclerosis. PMID- 1750225 TI - Cocaine alters heart rate dynamics in conscious ferrets. AB - This study was designed to test the hypothesis that cocaine intoxication induces distinctive alterations in sinus rhythm heart rate dynamics. Time-series and spectral analysis techniques were used to examine the effects of lethal doses of cocaine on heart rate variability in conscious, restrained ferrets. In all animals (n = 5), cocaine administration resulted in a marked decrease in sinus rhythm heart rate variability prior to sudden death. Heart rate variability (coefficient of variation of heart rate) just prior to death (0.018 +/- 0.005) was significantly (p less than 0.02) decreased compared to that at baseline prior to cocaine administration (0.061 +/- 0.022). There was also a significant (p less than 0.02) decrease in total spectral power prior to death compared to baseline. Transient low-frequency (0.04-0.10 Hz) oscillations in heart rate were also noted in three of the five animals following cocaine administration. There were, however, no significant changes in mean heart rate in response to cocaine. Alterations in heart rate dynamics were not seen in three saline-treated controls. Lethal effects of cocaine included ventricular arrhythmias (n = 2) and seizures (n = 3). One animal developed transient ST segment elevations that were consistent with coronary vasospasm. In conclusion, lethal doses of cocaine in the conscious ferret induce characteristic alterations in heart rate dynamics. These abnormalities (loss of heart rate variability and the appearance of low-frequency heart rate oscillations) are similar to those reported previously in certain patients at high risk of sudden cardiac death due to organic heart disease. PMID- 1750226 TI - Roentgen therapy for infections: an historical review. AB - Radiation was used extensively for the treatment of all types of infections before the advent of antibiotics. Although this mode of therapy is now in disrepute, radiation therapists of that era were firm believers in the ability of radiation to cure infections. A review of the literature suggests, but certainly does not prove, that low-dose local radiation, in the range of 75 to 300 roentgens, is an effective treatment modality for a wide variety of infections. Two then-prevailing rationales held that the effect was due either to radiation damage to the immune cells, causing stimulation of the immune response, or to the increase in local inflammation with resultant increased blood flow. Modern research has been limited but provides support for both arguments. Although there are no present indications for using radiation as therapy for infectious disease, a reasonable argument can be made from the available data that radiation is effective for the treatment of localized infections. The mechanisms of low-dose radiation as a treatment for infections remain unclear. The known and probable long-term sequelae of low-dose local irradiation preclude its common use for this condition. Nevertheless, it is hoped that this review will stimulate investigations into this relatively unexplored area of radiobiology. PMID- 1750227 TI - Ozone, air pollution, and respiratory health. AB - Of the outdoor air pollutants regulated by the Clean Air Act of 1970 (and recently revised in 1990), ozone has been the one pollutant most difficult to control within the federal standards. The known human health effects are all on the respiratory system. At concentrations of ozone which occur during summer air pollution episodes in many urban metropolitan areas of the United States, a portion of the healthy population is likely to experience symptoms and reversible effects on lung function, particularly if exercising heavily outdoors. More prolonged increase in airway responsiveness and the presence of inflammatory cells and mediators in the airway lining fluid may also result from these naturally occurring exposures. Serial exposures to peak levels of ozone on several consecutive days are more characteristic of pollution episodes in the Northeast United States and may be associated with recurrent symptoms. No "high risk" or more sensitive group has been found, in contrast to the case of sulfur dioxide, to which asthmatics are more susceptible than normals. The occurrence of multiple exposure episodes within a single year over many years in some areas of California has led to studies looking for chronic effects of ozone exposure on the lung. To date, no conclusive studies have been reported, although further work is under way. Much of what we know about the effects of this gas on the lung are based on controlled exposures to pure gas within an environmental exposure laboratory. Interactions between substances which commonly co-occur in air pollution episodes are also under investigation. PMID- 1750229 TI - [Percutaneous balloon valvuloplasty of pulmonary stenosis in childhood: early hemodynamic results and long-term Doppler echocardiography results]. AB - Pulmonary balloon valvuloplasty was performed in 35 children aged 3 days to 18 years (mean 4.5 years). Balloon/annulus ratio was 1.21 +/- 0.12. There were 6 infants less than 1 year of age (including 1 newborn), 4 with dysplastic valves and 4 with postoperative restenosis. Systolic transvalvular gradient showed a decrease of 69 +/- 14% from 68 +/- 15 mm Hg before to 21 +/- 11 mm Hg after dilatation (p less than 0.0001), and right ventricular pressure/systemic pressure ratio decreased from 0.8 +/- 0.29 to 0.4 +/- 0.15 (p less than 0.0001). Follow-up studies were performed in all patients up to 5 years (2.5 +/- 1.3 years) after dilatation. In 63% (22/35) follow-up period was more than 2 years (3.5 +/- 0.95 years). Doppler derived gradient had further decreased to 16 +/- 11 mm Hg (n.s.). Results in the 6 infants showed an immediate gradient relief of 71 +/- 11% from 85 +/- 4 mm Hg to 25 +/- 10 mm Hg (p less than 0.0001) with a further decrease to 20 +/- 10 mm Hg at follow-up. There were two early complications which had to be treated (tachycardia in WPW-syndrome, femoral vein dissection), no late complications were seen. The good immediate results and high persistent long-term success rate confirm balloon pulmonary valvuloplasty being the treatment of first choice for all patients in childhood. PMID- 1750228 TI - Effects of calcium channel blockers on potassium homeostasis. AB - The known effects of calcium channel blockers on various aspects of potassium homeostasis are reviewed. Regulation of potassium homeostasis requires both renal and external handling mechanisms. Signaling by calcium appears to mediate both of these. Calcium channels have been identified in adrenal glomerulosa cells, and cellular calcium entry has been demonstrated in vitro to be necessary for the synthesis and secretion of aldosterone. Calcium channel antagonists such as verapamil and nifedipine, at pharmacologic doses, can block aldosterone production. In vivo, however, only chronic administration of verapamil appears to attenuate aldosterone responsiveness to angiotensin II. Chronic administration of nifedipine does not have a dramatic effect on aldosterone production following potassium loading. Other studies have demonstrated improved extrarenal potassium disposal following treatment with calcium channel blocking agents. Clinically, there are no reports of either hyperkalemia or hypokalemia with the routine therapeutic use of these agents given alone. This review was prompted by the development of hyperkalemia in a patient with chronic renal failure following the initiation of therapy with the calcium channel blocker diltiazem: however, numerous other etiologies may also have contributed to the development of hyperkalemia in this case. Review of the data indicates that current evidence implicating this class of drugs in the pathogenesis of disordered potassium regulation remains equivocal. PMID- 1750230 TI - [Experiences with the Rashkind duct occluder]. AB - In five patients, aged from 34 to 64 years, a persistent ductus arteriosus was occluded transvenously with a Rashkind umbrella occluder. The diameter of the ductus ranged from 3.6 to 9 mm, the pulmonary artery pressure ranged from 20/4 to 55/25 mm Hg. Four patients had calcifications of the ductus wall. In one patient with a very large ductus a first occluder embolized into the pulmonary artery and was removed together with the introducer sheath. The ductus was occluded with a second umbrella. However, there was a residual shunt in this patient. In all other patients the procedure was successful without residual shunt. PMID- 1750231 TI - [Diagnosis by endomyocardial biopsy: angina pectoris as a manifestation of lupus erythematosus]. AB - A 64-year-old female patient with a prosthetic mitral valve suffered from recurrent typical angina and dyspnea. Left heart catheterization excluded a dysfunction of the prosthesis and coronary artery disease (CAD). A stress thallium scan demonstrated an ischemic reaction. An antimyosin scintigram was positive, indicating myocytal membrane disruption. Serological tests were suspicious for systemic lupus erythematosus (SLE). Therefore, an endomyocardial biopsy (EMB) was performed and a severe alteration of an intramyocardial artery, comparable with chronic SLE, was diagnosed. EMB is a useful diagnostic tool in patients with typical chest pain, positive thallium and anti-myosin scintigrams, however exclusion of CAD. PMID- 1750232 TI - [Diagnosis and classification of tricuspid valve insufficiency with dynamic magnetic resonance tomography: comparison with right ventricular angiography]. AB - To evaluate the diagnostic potential of magnetic resonance imaging (MRI) to diagnose and evaluate tricuspid incompetence (TI), right ventricular angiography (RVA) and MRI were compared in 51 patients. For angiographic semi-quantification a 4-grade modified Sellers classification was used. Several MRI-parameters (jet volume, jet area, number of slices with visible jet, duration of the regurgitation and volume of the right atrium) were examined concerning their validity to evaluate TI and compared to the angiographic data. Limits for MRI jet areas and volumes for each angiographic group were defined to obtain the best agreement with angiographic results. Thirty of 34 patients with angiographically visible TI (sensitivity = 88%) were diagnosed correctly with MRI. The 4 remaining patients also showed a small regurgitant jet which was, however, interpreted as physiologic. One of the 17 patients without angiographic TI was diagnosed as mild TI by MRI (specificity = 94%). MRI classification using jet volume (46/51 = 90% correct classifications) was not significantly better than the easier and faster MRI classification using jet area (43/51 = 84%). The other parameters (number of slices, duration of regurgitation and volume of the right atrium) showed considerable overlap between angiographic groups and did therefore not allow a classification into 4 grades. However, simple classification into hemodynamic relevant and irrelevant TI was possible. Thus MRI is able to diagnose TI with good sensitivity and specificity. Classifications based on jet volume and jet area showed good agreement with angiographic results. However, both parameters depend on the magnet and the pulse sequence used and must therefore be specifically determined for each imaging routine. PMID- 1750233 TI - [Diagnosis of arrhythmogenic right ventricular disease using magnetic resonance tomography]. AB - In our study, 12 patients with ventricular arrhythmias, but without any documented cardiac disease, and 10 healthy volunteers were investigated by spin echo magnetic resonance tomography (MRT) using a 0.5 Tesla magnet. Axial T1 weighted spin-echo sequences, as well as double angulated, multislice-multiphase sequences were acquired. Left- and right-ventricular volumes were then evaluated by outlining the endocardium in an end-systolic and an end-diastolic frame. The right-ventricular free wall and the right-ventricular outflow tract were investigated for myocardial thickness and intramural fat. PMID- 1750234 TI - [Principles, epidemiology and pharmacotherapeutic interventions in atherosclerosis]. PMID- 1750235 TI - [Apotheosis and tragedy of S. S. Iudin]. PMID- 1750236 TI - [Biomedical aspects of the use of cadaver blood]. AB - The author analyzes historical periods during which Academician S. S. Yudin developed the theory of cadaveric blood and pioneered its practical implementation, storage and the clinical use. Demonstrates the efficacy of the new transfusion medium in the management of patients with emergency conditions. Reviews 3 trends in the investigations carried out in this area: in morbid anatomy and forensic medicine, in experimental and clinical transfusiology, and in biomedical studies. Provides evidence for the fact that blood plasma of sudden death victims and perfusate of the vessels are specific raw materials for obtaining plasmakinase, a fibrinolytic agent, and fibrinogen degradation products as well as another source for obtaining preparations with a directed action. Based on a large factual material, the author shows the possibility, importance, prospects and efficiency of the use of components, preparations and biologically active substances from cadaveric blood plasma. PMID- 1750237 TI - [A goal-oriented local approach to the prevention of postoperative suppurative complications]. AB - A goal-oriented local approach to the prevention of postoperative purulent complications includes the use of compression suture devices to establish intestinal anastomoses and a complex of measures aimed at preventing surgical wound suppurations. To form compression anastomoses, use was made of the original AKA-2, AKA-4, IZhKA and SPTU devices fitted with compression clamps and of magnet facilities. The complex of measures to prevent postoperative wound suppurations includes optimal methods of laparotomy wound suture and the use of antibacterial suture materials, bathing of the wound by pulsed douche under pressure, local antibacterial prophylaxis by new dosage forms, preventive aspiration lavage and drainage of the wounds. Comparative clinical investigations carried out in more than 3,000 patients have demonstrated the effectiveness of the preventive methods under consideration and a decrease of the rate of postoperative wound suppurations from 11.7 to 2.3%. The rate of anastomosis failure amounted to 2.7%. PMID- 1750238 TI - [Use of fibrinolysis blood in patients with acute surgical diseases and injuries]. AB - S. S. Yudin paid much attention to the use of cadaveric blood in urgent medicine. While transfusing large amounts of blood (2-3 1) for pre- and intraoperative correction of hypovolemia, the danger of isoimmune reaction is reduced. Blood circulation measurement fluctuations while using both cadaveric and donor's blood are similar. However, the use of cadaveric blood helps correct hypercoagulation caused by some anesthetics. Cadaveric blood can be substituted for donor's blood. Besides, large amounts of cadaveric blood can be used from the same donor, which provides economic effectiveness. PMID- 1750239 TI - [Realization of the decisions of the 61st session of the General Meeting of the USSR Academy of Medical Sciences and further goals of the Academy]. PMID- 1750240 TI - [Plastic surgery of the pharyngo-esophageal junction as a new method of the surgical treatment of achalasia of the upper esophageal sphincter]. AB - Dramatic disorders of swallowing function of the central genesis (mostly because of cerebral circulatory disturbances) can be eliminated by surgery. Based on the first experience gained in this country with aphagia correction the author devised and employed a new method of surgical treatment--plasty of the pharyngoesophageal transition, providing beneficial short- and long-term results. PMID- 1750241 TI - [Surgical tactics in patients with postburn cicatricial esophageal stenosis]. AB - Surgical policy during the first years after burn was aimed at the recovery of natural nutrition. To achieve that, esophageal bougienage (503 cases) or total retrosternal esophagoplasty from the large intestine (192 cases) were performed. The authors hold that in order to attain complete medical rehabilitation for the patients, it is necessary to remove all the cicatricially changed tissues. Esophageal resection was performed in 78 patients, including 27 with preservation of the n. vagus. In the long-term postburn period, a problem arises as to the surgical correction of functional and morphological alterations associated with the establishment of artificial esophagus (80 cases including 35 patients who were operated on by S. S. Yudin). While choosing surgical policy it is necessary to take into account both the technical skills of a surgeon and the whole complex of changes in the patient's body, which have already developed and are going to develop in the future. PMID- 1750242 TI - [Effectiveness of the treatment of chemical burns of the esophagus by local endoscopic laser therapy]. AB - Overall 240 patients with chemical burns of the esophagus were examined. Local endoscopic treatment with the aid of lasers was applied in 180 victims. The efficacy of different types of laser radiation was compared in terms of the times of the healing of the esophageal wall. It is concluded that further studies should be carried out in the given area. PMID- 1750243 TI - [Pathogenetic bases of the use alpha-tocopherol and emoxypin in acute hemorrhage]. AB - The accumulation of lipid peroxidation (LP) products and decrease of alpha tocopherol (TP) content were demonstrable in the heart, lungs, kidneys and liver after acute blood loss. Injection of TP acetate inhibited LP and raised the content of endogenous TP in the heart, lungs and liver. The antioxidant emoxypin increased the reduced oxygen tension in the liver and kidneys after blood loss. The drug prevented the reduction of the glucocorticoid type II receptor level and increased the content of the type III receptors in liver cytosol of hemorrhagic animals. PMID- 1750244 TI - [Mechanisms of enteral correction of posthemorrhagic hypovolemia]. AB - It has been demonstrated in chronic experiments that after hemorrhage liquid absorption from the small intestine does not interfere with the process of its supply from the interstice. Totally both these processes considerably enhance the degree of autohemodilution. Infusion of the electrolyte monomer solution to the duodenum of the dogs which suffered hemorrhage (20-50 ml/kg bw) ensure, during the preserving of absorption function, a rapid and stable growth of the circulating plasma volume, proteins, sodium and potassium, being an effective means of steady replenishment of posthemorrhagic hypovolemia. Reduction of water retaining plasma components discovered in the experiments attests to the participation of the digestive organs in formation of the basic volemia substrate water-protein-electrolyte in volemic homeostasis maintenance. PMID- 1750245 TI - [Anthropogenic low-intensity environmental factors and life expectancy: new aspects of the problem]. AB - Based on their own universal concept of the causal relationship between chemical environmental agents and the human body, confirmed by numerous experimental data, the authors suggest that the biological process of aging may be accelerated or inhibited under exposure to chemical low-intensity environmental factors due to changes in the nonspecific resistance of the body. PMID- 1750246 TI - [Diabetes mellitus: facts and hypotheses]. AB - The paper summarizes the experience gained in examining diabetes mellitus and its complications in the experimental and clinical settings for many years. It forwards the basic aspects in the major problems of diabetology: etiology, pathogenesis, prevention, and therapy. The paper analyses the fate of some hypotheses advanced in different years and emphasizes new advances made in theory and practice of medicine. PMID- 1750247 TI - [Lung cancer and age factor]. AB - The authors provide the results of examination and treatment of 920 young patients under 45 (group I) and 462 elderly patients aged 60-74 years (group II). It has been revealed that in the young patients, primarily affected were the distal, proximal, intermediate and main bronchi. In group I patients, the tumor was localized in the intermediate or in the main (extrapulmonary) bronchus (in 6.9 and 9.8% of cases, respectively). In the elderly patients, the analogous data accounted for 2.7 and 1%, respectively. The segmental bronchi were more often involved in the patients of group II (11.3%) than in those of group I (5.3% of the cases examined). Analysis of the forms of lung carcinoma shows that in group I patients, the tumor was more often located near the root. Thus, in the young patients, the nodular peribronchial and peripheral (connected with the bronchus gap) forms of growth have been recorded in 34.1 and 25% of the cases examined whereas in the elderly patients, only in 14 and 13.1% of the cases. It has been noted that group I patients mostly demonstrated poorly differentiated carcinoma (47.6%) rather than high-differentiated epidermoid cancer (35.8%). Meanwhile high differentiated adenocarcinoma was seen only in 16.4% of the cases analyzed. In the elderly patients, the estimates were respectively 29.6, 59.0 and 11.2%. It should be emphasized that in young male patients, poorly differentiated carcinoma occurred 1.7 times more often that in group II patients (48.8 and 28.3%, respectively). PMID- 1750248 TI - [Structural bases of the barrier-protective function of the stomach and small intestine]. AB - The gastrointestinal tract acts as a barrier-protective tool in addition to its digestive and transport functions. The structural bases of the barrier protective function of the stomach and small intestine were shown in health, duodenal ulcer (DU), experimental gastroduodenal ulcers (GDU), vagotomy, and peritonitis in case of the interaction of these structures with parietal microflora (PM) which may be a valid criteria for assessing the barrier-protective function. PM increases in number in DU, GDU, vagotomy, and peritonitis. Various modifying interventions can normalize this parameter. Identifying the components of protective levels makes it possible to differentiate the affect of protective levels and makes it possible to differentiate affect some links of the barrier-protective function in order to restore it or prevent its disturbance. PMID- 1750249 TI - [Resolutions of the 62d session of the General Meeting of the USSR Academy of Medical Sciences]. PMID- 1750250 TI - Gestational diabetes in Papua New Guinea. AB - Pacific populations have some of the highest prevalences for diabetes in the world. Whilst universal screening for diabetes in pregnancy does yield the best pick-up rate it is not economically feasible in developing countries. Traditional risk factors have increasingly been shown to miss most gestational diabetes, particularly in populations for whom family history is unknown and obstetrical history not recorded. This study shows genetic origin to be a potent marker for gestational diabetes in a Pacific Island population. It is recommended that in Port Moresby 'at-risk ethnicity' (urban Motuan or Marshall Lagoon origin) be added to the list of indications for antenatal glucose tolerance testing in Papua New Guinean women. PMID- 1750251 TI - Motor development and nutritional status of young children in Madang, Papua New Guinea. AB - The relationship between nutritional status and motor development was investigated in a cross-sectional study of 457 0-2 year old children in Madang, Papua New Guinea. The median ages at which the major motor developmental milestones are attained are almost comparable to western populations up to 6 months of age. However, crawling and independent walking are slower to develop. At any given age children of higher nutritional status by weight for age (W/A), length for age (L/A) or weight for length (W/L) are more likely to have attained a given developmental stage than children of lower nutritional status. PMID- 1750252 TI - Betel-nut chewing may aggravate asthma. AB - A questionnaire survey on the relationship between chewing betel nut and asthma was carried out in 61 asthmatic patients who regularly attend a follow-up clinic at Port Moresby General Hospital. 54 of these had once chewed or were still chewing betel nut; 20 patients had already given it up, while 34 were still regular or occasional chewers. 7 patients had never chewed. 11 of the 20 patients who used to chew but had given up reported having stopped because of aggravation of their asthma. 22 of the 34 patients who still chewed also reported aggravation of their asthma by betel nut. Anecdotal reports were given directly linking specified methods of chewing the nut with asthma aggravation, in some cases indicating dose-response (toxicity) relationships. While more elaborate and objective studies are being undertaken, it is hereby suggested that patients with asthma be cautioned against chewing betel nut. PMID- 1750253 TI - Management of common potentially serious paediatric illnesses by aid post orderlies at Tari, Southern Highlands Province. AB - Systematic observations were made of a small number of aid post orderlies (APOs) managing children with the common but potentially serious symptoms of cough, fever and diarrhoea. On-site performance was evaluated against recommended management guidelines set out in Dr Keith Edwards' Diagnosis and Treatment of Common Childhood Illnesses for APOs. History taking at the aid post was brief and usually non-exploratory; examination of patients was often neglected. Drug prescription was generally appropriate for the diagnosis made, but drug dosages were often incorrect and treatment principles were rarely explained to guardians. Preventive health issues were rarely tackled. Our study reaffirms the need for on site assessment of the performance of paramedical workers, sets priority demands for continuing education of health workers, and provides a framework for competency-based problem-solving activities within this context. PMID- 1750254 TI - A survey of Papua New Guinea's health sector financing and expenditure. AB - As a result of increasing economic constraints in the health sector of Papua New Guinea, the Department of Health embarked upon a major financial policy review program in 1986, which incorporated several studies in key areas. This paper presents the results of one component of the review, a health sector financing and expenditure study, which was undertaken for the 1986 financial year. The study found that: 1) 88% of health sector expenditure was provided by the public sector; 2) over 95% of expenditure was used for recurrent costs and there was poor utilization of overseas aid for capital projects; 3) the balance of expenditure between primary and secondary health was appropriate; 4) there were regional inequities in expenditure; and 5) a disproportionate amount of recurrent expenditure was consumed by personnel costs. The need to increase nongovernment expenditure on health was identified and further investigation of alternative sources of financing the health sector is required. PMID- 1750255 TI - Supervision of rural health centres in Papua New Guinea: consolidation of the delivery of health services. AB - Aid posts and health centres remain the health facilities in most direct contact with the community in Papua New Guinea. The planners of health services have well accepted the difficulties of adverse geography and sectoral differences, and adapted a method of delivery which is efficient and appropriate for all levels of health personnel. Those peripheral staff, however, have been left to their own devices. It should be considered that the continued success and achievement of the milestones of health care in Papua New Guinea require close surveillance and support at the basic level. Intensive supervision is essential to the consolidation and progress of existing health services. PMID- 1750256 TI - The diagnosis and management of common forms of arthritis in adults in Papua New Guinea. AB - Reactive arthritis is the leading cause of arthritis in Papua New Guinea, followed probably by gonococcal arthritis. Indomethacin and local hydrocortisone acetate are useful in the treatment of reactive arthritis. Refractory cases of reactive arthritis may be helped by weekly low-dose oral methotrexate or by long courses of doxycycline. When Neisseria gonorrhoeae is thought to be involved treatment should cover penicillinase-producing strains. Infective arthritis due to Staphylococcus aureus and Mycobacterium tuberculosis is less common but should be considered in all patients because prompt and specific treatment is required to avoid permanent damage. PMID- 1750257 TI - Making family planning more effective--Papua New Guinean style. PMID- 1750258 TI - Primary amoebic meningoencephalitis in the Western Province. AB - Six cases of primary amoebic meningoencephalitis were diagnosed and treated at the Balimo Health Centre between December 1986 and September 1988. This disease has not previously been reported in Papua New Guinea although from information derived from other studies it should be occurring in the lowlands of Papua New Guinea from time to time. Although less than optimum treatment was given to the early cases the case fatality rate in the series was only 66%. This compares very favorably with a case fatality rate of nearly 100% from other studies. Early diagnosis and prompt treatment should help to reduce mortality. PMID- 1750259 TI - Impaired cell-mediated immunity in Papua New Guinean infants. AB - Immune function was studied in Papua New Guinea highland infants with pneumonia, healthy highland controls and expatriate controls under the age of 15 months. Delayed-type hypersensitivity to tuberculin was depressed in highland pneumonia patients and highland controls as were CD4/CD8 T-lymphocyte ratios. The differences between highland and expatriate infants were more pronounced after 6 months of age, suggesting an environmental effect. Serum immunoglobulin and complement concentrations were higher in highland infants than in expatriate controls. Indices of nutritional status were similar in highland and expatriate infants but iron deficiency was more common in the highland infants in the study. PMID- 1750260 TI - The aetiology, management and prevention of acute respiratory infections. PMID- 1750261 TI - Control of acute respiratory infections in children in Papua New Guinea. PMID- 1750262 TI - Mortality and morbidity from acute lower respiratory tract infections in Tari, Southern Highlands Province 1977-1983. AB - Monthly demographic surveillance by village reporters has been ongoing in the Tari Basin since 1970. Cause of death is ascertained by verbal autopsy. 20% of deaths between 1977 and 1983 were from acute lower respiratory tract infection (ALRI). ALRI mortality rates were highest in the very young and the elderly and have risen since the early 1970s but declined in the 1981-1983 period when pneumococcal vaccine was being tested in Tari. 44% of ALRI deaths in children under 5 years of age occurred before the age of 6 months but ALRI mortality remained high during the second year of life. Utilization of health services before death was highly age-dependent, with the vast majority of young children but few elderly people receiving some form of medical attention. However, less than half the children who died of ALRI received inpatient care. Fortnightly morbidity surveillance of children between 1981 and 1983 showed that ALRI was the commonest cause of severe morbidity; children suffered 2-3 episodes of ALRI in the first year of life, 20% of which were moderate or severe disease. Improved case management, nutritional status and hygiene in addition to good coverage with pertussis and measles vaccines and immunization with efficacious pneumococcal and H. influenzae vaccines are required to reduce mortality and morbidity from ALRI. PMID- 1750263 TI - The bacteriology of acute pneumonia and meningitis in children in Papua New Guinea: assumptions, facts and technical strategies. AB - Acute respiratory infections in children aged less than 5 years in the Eastern Highlands of Papua New Guinea were investigated bacteriologically for 10 years from November 1978. Haemophilus influenzae and Streptococcus pneumoniae were responsible for 73% of all bacteria cultured from lung aspirate (83 samples), 85.5% from blood (1024 samples) and 92% from cerebrospinal fluid (155 samples). Nonencapsulated H. influenzae was carried by up to 90% of children and was the predominant haemophilus type cultured from lung tissue. Mixed infections of the lung with two types of H. influenzae (8 cases) and both H. influenzae and S. pneumoniae (18 cases), commonly together with other organisms of questionable pathogenicity, reflected the proximity of this organ to the upper respiratory tract. Serotype b accounted for 62% and 82% of H. influenzae isolated from bacteraemic pneumonia and meningitis cases, respectively. Polymicrobic bacteraemic pneumonia occurred in 16 children. Both H. influenzae and S. pneumoniae establish dense, unregulated long-term colonization in the nasopharynx during the neonatal period. Each inhibit autochthonous microflora by mechanisms that are currently unclear. Infections with two or more types occur in 30% (S. pneumoniae) and 60% (H. influenzae) of carriage-positive children. 70-75% of H. influenzae and S. pneumoniae isolates from blood concomitantly colonize the upper respiratory tract. Intense exposure of Papua New Guinean children to penicillin at all levels of health care since the 1940s has resulted in widespread relative resistance among pneumococci to this antibiotic. Resistant strains are now found in 32 serotypes, and in children penicillin resistance is present in 75% of all carriage strains and 52% and 22% of blood and cerebrospinal fluid isolates, respectively. Penicillin-susceptible and resistant pneumococcal serotypes commonly coexist in multiply populated carriage sites. Resistance to betalactam antibiotics is rare among H. influenzae strains and resistance has not been detected in either H. influenzae or S. pneumoniae to chloramphenicol, erythromycin, tetracycline or cotrimoxazole. It should not be assumed that the technology of respiratory bacteriology as it is practised in developed countries can be transferred to the third world for utilization in paediatric aetiology and carriage studies. Respiratory bacteriology strategies as they evolved in Goroka were subject to diverse influences. The type distribution of the major causative agents defied fashionable beliefs, generated the need for more precise epidemiological differentiation and, by virtue of their carriage density, cultural properties and response to commonly used antibiotics, required the introduction or development of compatible diagnostic procedures. PMID- 1750264 TI - Influenza virus activity in Papua New Guinea. AB - Influenza viruses remain a major cause of respiratory disease in both developed and developing countries. A great deal of information concerning the structure, pathology and modes of transmission of these viruses has been accumulated, but no means of successfully combating them have, as yet, been devised. The most appropriate strategy for limiting the effects of influenza is to monitor the emergence and spread of new strains carefully and warn the public and at-risk groups of impending epidemics. In Papua New Guinea, as in most other developing countries, the major at-risk groups are the very young and the elderly. In the past, influenza epidemics were rare and affected the whole community, but with modern development and increased mobility the transmission dynamics of influenza have changed. The only influenza surveillance centre in Papua New Guinea is at the Papua New Guinea Institute of Medical Research in Goroka, and the surveillance activities of this centre are limited to the immediately surrounding areas. There is a need to establish a national influenza surveillance network, to provide nation-wide monitoring of influenza activity, and to provide a central repository of current information on influenza infections in the country. PMID- 1750265 TI - Acute respiratory infections in Australian Aboriginal children: current knowledge and future requirements. AB - Although inadequately documented, it is clear that acute respiratory infection (ARI) is a major cause of morbidity and hospitalization in Australian Aboriginal children. ARIs continue to cause substantial mortality in Aboriginal children, and they are likely to cause a variety of potentially serious sequelae. The literature emphasizes the importance of pneumonia as a cause of hospitalization of Aboriginal children. There is good evidence that Streptococcus pneumoniae and Haemophilus influenzae are predominant causes of severe pneumonia, but little is known about the importance of other respiratory pathogens, such as respiratory syncytial virus, as causes of ARI in Aboriginal children. Poor living conditions, low birthweight and malnutrition are likely to be important risk factors for ARI in some groups of Aboriginal children. Although broad-ranging economic and environmental changes will be required to bring about a sustained reduction in ARI in Aboriginal children, there should be an emphasis upon correct case management of ARI at the primary care level so as to reduce the need for hospitalization. Some research priorities are discussed. PMID- 1750266 TI - Immune function risk factors for acute lower respiratory tract infections. AB - The immune response of pneumonia patients and controls to Streptococcus pneumoniae was investigated by enzyme-linked immunosorbent assay (ELISA). Patients less than 6 months of age had significantly lower levels of anti pneumococcal polysaccharide antibodies than their age-matched controls. Patients and controls 6-14 months of age had lower antibody levels than the children 0-5 months of age. Adult patients and controls did not differ in their antibody status. However, patients and Papua New Guinean controls had depressed cell mediated immunity and low T-cell numbers. Low levels of antibodies to pneumococcal polysaccharides in children less than 6 months of age appear to be an important risk factor for acute lower respiratory tract infections but other factors may be important in older infants and adults. PMID- 1750267 TI - Health systems research and acute respiratory infections: essential focus on the health system. AB - Health systems research is receiving increasing prominence in the developing world as an aid to decision-making. In acute respiratory infection (ARI), health systems research has focused on alternative means of educating mothers to recognize pneumonia and seek treatment and on improving the case management practices of health workers. While these interventions have demonstrated their effectiveness in reducing ARI mortality in the research setting, on a wider scale the management and control of ARI will depend on a well-functioning health system, with skilled workers, essential drugs and equipment, an operating referral system, adequate supervision and an active monitoring system. The essential focus for health systems research in the reduction of the impact of ARI on public health in Papua New Guinea should be on improving the effectiveness of the health care delivery system. Some potential areas for health systems research are outlined. PMID- 1750268 TI - Clinical management of acute respiratory infections and measles in Papua New Guinea. PMID- 1750269 TI - [Low dose ionising radiation and cancer: findings and methods. Report of a meeting and consequences for Switzerland]. AB - Today's society is concerned about the dangers of ionising radiation, especially in the aftermath of Chernobyl. On the other hand, there exists a widespread lack of understanding radiation biology and radioepidemiology--the very sciences which provide the data from which today's risk estimates have been derived. The papers in this issue of the Journal were presented at a workshop on "Low level radiation and cancer: data and methods" held on 10th-11th December in Feuisberg, near Zurich. The meeting was organised by the Institute of Social and Preventive Medicine of the University of Zurich under the auspices of the Swiss Federal Office of Public Health. Its aims were threefold. First, to give an introduction to some basic facts and methodological issues in radiation physics, biology and epidemiology. Secondly, to give an overview of the availability of data for radioepidemiological research in Switzerland and, thirdly, to evaluate possible research strategies in this country. A list of some notions and units commonly used in the radiation sciences serves an an introduction to the field (G. Schuler et al.). In using units and notions it is important to distinguish the description of biological experiments and epidemiological observations from definitions and risk projections proposed by international reports and consensus bodies for radioprotection purposes. The next papers deal more specifically with selected aspects of the basic sciences. Dosimetry means quantifying the physical effects of ionizing radiation in human tissue; this is not a straight-forward procedure (I. Cordt). The foundations of general radiation biology are succinctly summarised by C. Michel. An account of our present knowledge and theories of radiation carcinogenesis is provided by W. Burkart. W Lutz compares dose-response models of chemical carcinogenesis with those used in radiation carcinogenesis. During the last decade the epidemiological foundations of radioprotection have changed considerably. Longer follow-up studies have become available from the atomic bomb survivors and fro other cohorts. A new dosimetry system (DS 86) has been introduced for Hiroshima and Nagasaki. Exposure to domestic radon has become a major focus of interest. Not only the data, but also the methods of analysis and modeling of risks have evolved, as shown by the recent reports of national and international scientific committees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750270 TI - Some notions and units in radioepidemiology and radiation protection. A structured list for the epidemiologist. AB - An annotated list of some notions and units used in radioepidemiology is presented, with special emphasis on differentiating between the realms of radiation physics, radiation biology, radioepidemiology and radiation protection. PMID- 1750271 TI - Comments on radiation dosimetry and linear energy transfer. AB - The quantification of the physical effects of ionizing radiation in human tissue is the basis of risk assessment. This quantification results from determination of kerma or absorbed dose. The procedure for the absolute determination of absorbed dose with an ionization chamber is discussed. The biological effects of ionizing radiation are dependent, not only on the absorbed dose but also on a second physical parameter, the linear energy transfer. PMID- 1750272 TI - Radiobiological fundamentals in radioepidemiology and radiation protection. AB - Radiation is a convenient tool to study fundamental processes of life. Biological effects of irradiation may result from indirect actions which are mediated by free radicals (e.g. OH-radicals) or from direct actions which involve ionizations in the DNA and other biomolecules. Damage to the DNA is the principal, but not exclusive target for cell death, loss of reproductive integrity, mutation, cancer, developmental anomalies and other radiobiological effects. Repair of damaged DNA and cellular recovery processes play an essential role in affecting the survival of cells. Dose, dose rate, radiation quality, biological and chemical modifiers also have a pronounced effect upon the extent of radiation responses. The biological effects of ionizing radiation are somatic or hereditary and can further be classified into stochastic and deterministic effects. For radiation epidemiology and protection the stochastic action is more relevant because the probability of an effect is a function of dose, without a threshold. Induction of cancer, hereditary diseases and probably also mental retardation are regarded as stochastic effects. PMID- 1750273 TI - From energy deposition to cancer. AB - Recent progress in molecular biology, genetics and microdosimetry has considerably increased our knowledge of the mechanisms of radiation-induced carcinogenesis. However, as a result of the complexities involved in the many genetic and epigenetic changes in cells leading to the expression of malignancy only years or even decades after radiation exposure, risk coefficients for the quantification of health detriment still have to be derived largely from epidemiological data and animal studies. On the other hand, improved understanding of molecular and cellular mechanisms is increasingly important in testing and refuting hypotheses about the relative carcinogenic potential of different radiation qualities and dose rates, and of low-level exposures. PMID- 1750274 TI - Dose-response relationship for chemical carcinogenesis by genotoxic agents. AB - Formation and repair of DNA adducts from genotoxic carcinogens is expected to be proportional to dose as long as the rates of the enzymatic and non-enzymatic activation and inactivation reactions are all proportional to the substrate concentration. Deviations from linearity are expected in situations of induced and saturated kinetics. A sublinear shape of the dose-response curve is always expected at toxic dose levels when regenerative hyperplasia accelerates the fixation and accumulation of mutations resulting from the DNA adducts. In a heterogeneous population, however, a nonlinear dose-response curve is linearized when genetic and life-style factors result in individual variability in the rates of the activation and inactivation pathways. Finally, in the light of the endogenous and therefore partly unavoidable nature of genetic damage, it is proposed that the cancer risk from exposure to an exogenous carcinogen should be expressed as a reduction of tumor-free life span rather than in absolute terms of additional cases. PMID- 1750275 TI - Projecting radiation-induced cancer risks across time and populations. AB - Various methods can be used to project the risks of radiation-induced cancer estimated in cohort studies beyond the period of follow-up and to other populations. The epidemiological evidence for the choice of risk projection model is reviewed based on data from studies such as those of the Japanese atomic bomb survivors and UK ankylosing spondylitis patients given x-ray therapy. The results of risk projections based on various approaches are presented, including those suggested by UNSCEAR and by the BEIR V Committee. It is emphasised that the continued follow-up of populations such as the Japanese atomic bomb survivors is of great importance in estimating lifetime risks, and that further parallel analyses are required to examine how risks vary across populations. PMID- 1750276 TI - Lung cancer and alpha radiation. AB - The considerable radiosensitivity of the human lung together with the highly localized alpha-doses in the bronchial and pulmonary regions from naturally occurring and man-enhanced radon decay products make the respiratory tract the most critical organ for cancer from exposure to ionizing radiation in our environment. From indoor radon, the tracheobronchial region of the lung generally receives radiation doses which are at least an order of magnitude above the total dose to any other organ. Excess lung cancer deaths found in epidemiological studies on heavily exposed populations of miners can be fitted reasonably well to a relative risk model, when declines in relative risk with both age at risk evaluation, and time since exposure, are incorporated. Smoking seems to act synergistically. A comparison of the major radon risk projections shows considerable discrepancies in the best estimates of risk, indicating that the uncertainties remain large. PMID- 1750277 TI - Radiation-induced thyroid neoplasia. AB - Thyroid cancer is a well documented late effect of exposure to ionizing radiation. The excess risk begins 5-10 years after exposure and continues until at least 40 years after exposure. Females are roughly three times more susceptible to both radiogenic thyroid cancer and to thyroid cancer of other origins than are males. Therefore, relative risk estimates for radiogenic thyroid cancer do not necessarily differ by sex. The excess risk is higher among children exposed prior to five years of age than in those exposed later. The risk for radiogenic cancer following exposure to 131I appears to be lower than that following exposure to high dose-rate external irradiation, and in the Swedish diagnostic study 131I was nearly one fourth as efficient as external X-rays in inducing thyroid cancer. The Swedish data suggest that 131I is substantially less efficient in inducing thyroid cancer than high dose-rate exposures. In that study, however, 95% of the exposed individuals were 20 years or older (mean age 45 years). PMID- 1750278 TI - Approaches to investigating clusters: by example, childhood leukaemia near Sellafield. AB - There is occasionally concern about suspected clusters of disease in geographically localised areas among members of the general public or other groups. These occurrences need a systematic approach to their investigation. Such an approach needs to consider the definition and characteristics of the cluster and of the putative environmental cause for concern. Depending on the outcome of these considerations there will be different actions, possibly involving epidemiological studies. The necessary components of the approach and resulting actions are outlined in this paper, and illustrated by the example of childhood leukaemia rates around the Sellafield nuclear plant. PMID- 1750279 TI - Epidemiological designs in radioepidemiological research. AB - Most of the information currently available on radiation effects comes from the observation of individuals who received high doses, either from one acute exposure or a series of exposures. Because of the uncertainties in extrapolating risks from these studies to the exposure circumstances of most cancers today (in particular, low-level environmental exposure), direct epidemiologic studies of populations receiving low doses chronically are needed. The effects which we want to quantify are likely to be small, however, and extreme care must therefore be put into the design of such studies if they are to be informative for risk assessment purposes. The areas of particular importance in designing risk assessment studies are reviewed. The advantages and limitations of various epidemiological study designs, and the problems and importance of dosimetry are discussed. Examples from the recent epidemiological literature are presented to illustrate the discussion. PMID- 1750280 TI - Components of total irradiation dose in Switzerland and their ranges. AB - The present knowledge about dose components in Switzerland and their ranges is reviewed. Considerable ranges are found for doses induced by radon decay-products and by cosmic and terrestrial radiation. Yearly doses from radon decay-products show average values between about 1 and 20 mSv in different communities and individual values up to about 150 mSv. The reliability of these average values is, however, limited, because radon concentrations have been measured up to now only in a small number of houses, and because corrections of the raw data are necessary, increasing the uncertainty of the results. Doses from terrestrial and cosmic radiation show locally variable values between about 0.5 and 1.5 mSv per year. These doses are mainly derived from outdoor measurements. Therefore, these results also are only of limited use in possible epidemiological applications. PMID- 1750281 TI - Dosimetric data on radiation workers in Switzerland: availability and limitations for epidemiological research. AB - In 1990 the Swiss National Dose Registry started a test phase of data collection and processing. The question has been raised whether this new, centralised database with its computerized, easily obtainable data on occupational radiation exposure in Switzerland can be used for radioepidemiological studies. This paper sketches the organisation of personal dosimetry in Switzerland, describes the dose registry and other dosimetric data sources and discusses their suitability and limitations for radio-epidemiological studies. PMID- 1750282 TI - Medical prophylaxis for Swiss nuclear workers. AB - Medical prophylaxis for Swiss nuclear workers is prescribed by law, as for all other persons occupationally exposed to radiation. Medical examinations including questions about the personal history, a physical examination and blood counts take place on entering the job and each year thereafter. Follow-up after leaving the job is not done. With the coming new legislation, medical prophylaxis will be better adjusted to the latest requirements. PMID- 1750283 TI - The "post-Chernobyl" childhood leukemia study (ECLIS Study). AB - Numerous European cancer registries are working together to evaluate the current trends in the incidence of childhood leukemias after the Chernobyl accident. The study is coordinated by the International Agency for Research on Cancer. The primary objective is to establish whether the accident has resulted in an increase in the number of cases. The results will also allow an evaluation of the clusters which could be reported. According to the provisional estimations, the accident could lead to an increase of an average of 0.8% of the frequency of new cases in the European regions covered by the study. For the whole of Switzerland, this increase would correspond to 0.5 supplementary cases per year. PMID- 1750284 TI - [Diagnosis and therapy of malignant thyroid diseases]. AB - The clinically important malignancies are characterized on the basis of 257 primary surgical procedures performed between 1973 and 1990 (9.1% of all thyroid operations during this period). Our own proceeding is characterized both in diagnostics and surgical technique in primary and recidive operations under special regard of a modified lymph node dissection. Obligatory and facultative adjuvant therapies are described. The follow-up schedule, which has found to be essential for the individual prognosis, should be discussed. PMID- 1750285 TI - [Spinal metastases of differentiated thyroid cancers. Disease picture, diagnosis, therapy]. AB - Thyroid malignancy should be ruled out, whenever an osteolytic lesion in the spine is detected. In the presence of a single bone lesion, surgical procedure should be the treatment of choice. Even if these patients will not be "tumour free" after the orthopedic correction they can live without pain and no mobility problem. PMID- 1750286 TI - [Diagnosis and interdisciplinary therapy of spinal cord compression caused by spinal metastases]. AB - Metastatic tumours of the bone system occur up to 60% in the spinal cord. The epidural spinal cord compression is also found by metastatic tumour, so patients with metastatic disease in this localisation carry a poor prognosis. From 1986 to 1988 35 patients with symptomatic spine metastasis are operated upon. 43% of these patients recover their capability of walking. 90% from the operated collective show a reduction of pain. The primary tumour is first found from cancer of the lung and second from the kidneys. The most common localisation of metastatic tumour is the thoracic spine. The ratio from male to female is 2:1. If the risk of operation and differential therapy is discussed, the decompression and tumour resection will be the first. The concept for postoperative mobilisation and therapy concludes the stabilisation of spinal cord with internal fixation. Treatment of metastatic tumours takes aim at the improvement of life quality. PMID- 1750287 TI - [Evaluation of thyroid gland scintigraphy and thyroid gland ultrasonography from the surgical viewpoint]. AB - The results of thyroid ultrasound and scanning on 251 patients have been reviewed in regard of the postoperative histological findings. Both procedures (thyroid ultrasound and scanning) cannot predict the histology. But with ultrasound adenomas of the thyroid for example could be localized in 93%, with isotope scanning only in 74%. Merely 2% of cold nodules with decreased or mixed sonographic pattern have been malignant. Ultrasonography is extremely helpful for the surgeon in his operative planning. PMID- 1750288 TI - [Atypical thyroid gland adenoma. Experiences during 12 years struma surgery]. AB - In a period of 12 years atypical adenomas were found in 82 cases and thyroid carcinomas were diagnosed in 93 patients in the main group of 2176 patients undergoing a thyroid resection. Mean age was 46.5 years for atypical adenomas and 48 years for carcinomas. In 76.8% of the cases with atypical adenomas the postoperative course and long term results were followed up. None of these patients developed a recurrence or malignancy. 93.3% of the patients were treated with Levothyroxin for prevention. Hyperthyroidism did not occur pre- or postoperatively. PMID- 1750289 TI - [Reoperations in primary hyperparathyroidism]. AB - We report on 14 patients suffering from persistent (n = 13) and truly recurrent (n = 1) primary hyperparathyroidism. Reoperations were successful in 13 cases. Cervical reexploration was only required for 5 patients who had previous operations by unexperienced surgeons in other clinics. In 5 out of 7 patients operated by us, the causes of the persistent primary hyperparathyroidism were 4 adenomas and one hyperplastic gland in the mediastinum found by median sternotomy. The remaining cases were a rare ectopic location of the inferior glands and an inadequate resection in four-gland-hyperplasia. Preoperative localization procedures were carried out for most patients. 201-Tl/99m-Tc subtraction scintigraphy has proved for localization in both the cervical region and the mediastinum to be a highly sensitive method. Reoperative parathyroid surgery can be reduced with thorough initial cervical exploration by experienced surgeons in specialized clinics. PMID- 1750290 TI - [Improved survival rate of postoperative renal failure caused by high volume hemofiltration]. AB - Continuous arteriovenous hemofiltration is the treatment of choice for postoperative acute renal failure (ARF). The clinical value of two different treatment modalities (spontaneous vs. pump-driven hemofiltration PDHF) were compared in two groups of patients with postoperative ARF. There were no differences in both groups regarding age, duration of treatment, severity of illness or cause of renal failure. The survival rate of patients treated with PDHF was significantly higher (29.4 vs. 12.5%). PDHF also led to a significantly larger daily ultrafiltrate volume (15.6 +/- 1.9 vs. 7.0 +/- 0.4 l/d, p less than 0.05). The accelerated elimination of toxic mediators through the filtration membrane in high-volume filtration using a pump system (PDHF) may have been responsible for the improved survival rate. PMID- 1750291 TI - [Animal experiment studies of the distribution and elimination of radioactively marked endotoxin]. AB - We were able reproduce typical morphological and laboratory changes of endotoxinemia in dogs and small experimental animals by administration of E. coli = 111 K58 endotoxin labelled with 99m Tc. Contrary to the literature our distribution studies in rats showed a high concentration of endotoxin in the kidney. An effective endotoxin elimination was possible by extracorporal hemoperfusion in vitro and vivo. Optimal results were achieved using immunoabsorption in combination with plasmapheresis. However, further experimental studies are necessary to clarify the problem fully. PMID- 1750292 TI - [The colloid osmotic pressure of blood. Physiology, measuring technique and pre analytic factors of influence]. AB - Since the fundamental work of Starling the central of colloid osmotic pressure for maintaining volume homoeostasis and for transcapillary fluid exchange has been well known. To treat an intravasal volume deficit colloidal plasma substitution solutions are able to secure a sufficient colloid osmotic pressure. The last one can be measured by oncometry. Therefore an individual therapy is possible. This review describes the physiologic function, measurement techniques and important influencing parameters and disturbing factors which may be taken into consideration when colloid osmotic pressure is determined. PMID- 1750293 TI - [Experiences with synthetic laparotomy frames]. AB - Report about good experiences with frames for laparotomy made with synthetic material. They reduce bruise of abdominal wall and pressure lesions of femoral nerve. PMID- 1750294 TI - [Report on the 6th International Congress on infections in gynecology and obstetrics, 13-16 February 1991 in Munich]. PMID- 1750295 TI - [Chronic recurrent vaginal candidosis]. PMID- 1750296 TI - [The cardiovascular system in pre-eclampsia. Pathophysiology and sequelae to be treated]. AB - Physiologic alterations of the cardiovascular system during normal pregnancy are the basis of all discussions about the problem of preeclampsia and treatment. The main point has to be the sufficient blood supply to the fetus. In this review cardiovascular alterations in high and low pressure system have been reported. High arterial blood pressure, elevated total peripheral resistance, reduced plasma volume, hemoconcentration, reduced suspension stability and hyperviscosity are symptoms which can be treated. Clinical experiences with a hemodynamic adjusted treatment, giving firstly infusionary therapy for correcting hypovolemia with the aim of an improvement within the low pressure system which cause an increase of cardiac output and then secondly the use of only such antihypertensive drugs having favourable effects on the uteroplacental blood flow are good and confirm theoretical considerations. PMID- 1750297 TI - [Therapeutic aspects of trichomonas infection of the female genitals]. AB - Infection with trichomonas is a common event in patients in gynecologic practice. In patients in an outpatient department the incidence of trichomonas infection was 7%, in cases with other genital infections 16%. Especially in alcalic vaginal milieu and in Gardnerella infections higher rates of trichomonas could be observed. The recurrence rate after monotherapy was 8%. PMID- 1750298 TI - Serum concentration of secretory IgA during pregnancy and in gynaecological diseases affecting glands and mucosas. AB - Secretory IgA (S-IgA) was measured in serum samples from pregnant women by means of radial immunodiffusion according to Mancini with an antiserum against the secretory component and an S-IgA standard. The results neglect the differentiation in SC, S-IgA, and S-IgM. The study includes S-IgA serum levels during pregnancy and post partum as well as in patients with cervical carcinoma and inflammation of the genital tract. The S-IgA serum levels of pregnant women (2nd and 3rd trimester) and after delivery were increased significantly in comparison to nonpregnant women (p less than 0.01). The S-IgA levels in genital inflammation diseases and cervical carcinoma were only sometimes elevated. Pregnant women, 1st trimester: means = 40.0 mg/l (s = 12.2); pregnant women, 2nd trimester: means = 60.13 mg/l (s = 18.9); pregnant women, 3 rd trimester: means = 73.5 mg/l (s = 17.4); post partum: means = 77.5 mg/l (s = 29.52); cervical carcinoma: means = 41.9 mg/l (s = 17.3); adnexitis: means = 46.46 mg/l (s = 16.8); controls: means = 38.61 mg/l (s = 10.5). In a second part S-IgA could be estimated in serum samples of pregnant women by means of an enzyme-linked immunosorbent assay (ELISA). The levels ranged from 7.1 mg/l to 19.3 mg/l in the 1st trimenon and from 16.8 mg/l to 82 mg/l in the 3rd trimenon (means = 11.72 mg/l; s = 4.419; n = 21 and means = 40.01 mg/l; s = 15.117; n = 60). This increasing was significant too (p less than 0.01). PMID- 1750299 TI - [Morphologic studies of endometrial cancer for biological assessment of nuclear grading]. AB - Three hundred and eighty-three cases of endometrial carcinoma stage pT1NxM0 had been reviewed retrospectively by making use of histo- and cytomorphological studies. The carcinomas were re-classified and histological and cytological gradings, independent from each other, have been carried out. Typical tumor characteristic of the nucleus (nuclear grading) and their biological importance have been described compared with morphological factors of prognosis (typing, histological grading, depth of myometrial invasion, lymph- and blood vessel invasion). Interrelations and discrepancies between histological and nuclear grading will also be described. PMID- 1750300 TI - Long term care inservice resource centres. PMID- 1750301 TI - 1991--75th Anniversary AARN. Our history--a proud heritage 1980-1991. PMID- 1750303 TI - Writing a research grant for AFNR: talk to someone first. PMID- 1750302 TI - Graduate education: the first step. PMID- 1750304 TI - A Christmas gift: valuing nursing. PMID- 1750305 TI - Barer-Stoddart Report: toward integrated medical resource policies for Canada. PMID- 1750306 TI - Scheduling satisfaction: a job enhancement project Medicine Hat Regional Hospital. PMID- 1750307 TI - Beneficial effect of sodium sucrose-sulfate on the ocular surface of patients with severe KCS in primary Sjogren's syndrome. AB - Sucralfate (aluminium sucrose-sulfate), a well known gastric mucosal protectant, has been tested topically on 22 patients (20 females and 2 males) suffering from primary Sjogren's syndrome. Median treatment period was 6 months (range 1-19 months). Statistically significant improvement in the ocular surface condition was found judged from the reduction in Rose-Bengal score (P less than or equal to 0.00005). The beneficial effect appeared within the first 1-4 months of treatment. No adverse side effects were encountered. PMID- 1750308 TI - Correlation of conjunctival impression cytology results with lacrimal function and age. AB - Impression specimens were obtained from the bulbar conjunctiva of 146 eyes of 73 healthy volunteers (mean age, 52 years). Goblet cell densities and nuclear cytoplasmic (N/C) ratio were determined. Break-up time (BUT), Schirmer-I test (S I), Rose Bengal scores (RBs) were also recorded. Using a simple linear regression analysis, no correlation between the number of Goblet cells and age, BUT and S-I was found. Negative correlation with RBs (P = 0.05) was found. The N/C ratio has a negative correlation (P less than 0.01) with age and RBs and a positive correlation with BUT (P less than 0.01) and S-I (P = 0.03). PMID- 1750309 TI - Plasminogen activator inhibitors in human tears. AB - Plasminogen activator inhibitor activity was demonstrated in tears of patients suffering from various corneal and conjunctival diseases. Active plasminogen activator inhibitor was also detected by reverse fibrin zymography in tears of a patient suffering from Sjogren's syndrome and in those who underwent eye surgery. Immunoblotting revealed that both type 1 and type 2 plasminogen activator inhibitors may be present in human tears when the epithelial cells of the cornea and conjunctiva are affected and/or the permeability of the conjunctival blood vessels is increased. The molecular weight of inhibitors suggested the simultaneous presence of both free and activator-complexed inhibitors. However, no plasminogen activator inhibitor was detectable in normal human tears, suggesting that the presence of plasminogen activator inhibitors in tears may be associated with the pathological events at the ocular surface. PMID- 1750310 TI - A comparison of the precorneal residence of an artificial tear preparation in patients with keratoconjunctivitis sicca and normal volunteer subjects using gamma scintigraphy. AB - The precorneal residence of an artificial tear preparation has been compared in twelve patients with keratoconjunctivitis sicca (KCS) and twelve normal healthy volunteers. The artificial tear solution was radiolabelled by the inclusion of 1 MBq technetium-99m diethylenetriaminepentaacetic acid (99Tcm-DTPA), and 25 microliters was instilled into one eye only. Deposition of the preparation was followed by gamma scintigraphy. Precorneal clearance of the solution was found to follow bi-exponential kinetics in all subjects with no significant differences in clearance rates between the two study populations. There was also no significant difference in the area under the time-activity profile for the two study groups. This suggests that the reduced reflex tearing and basal lacrimation in KCS patients, indicated by the Schirmer's test, are not important in the clearance of isotonic solutions from the eye surface. PMID- 1750311 TI - Long-term prognosis of pigmentary glaucoma. AB - Outcome, prognosis and course of pigmentary glaucoma were studied in 38 patients (75 eyes). The mean age of the subjects at the time of diagnosis was 34.0 years and at the time of the study 44.1 years. The follow-up time ranged from 2 to 30 years with a mean follow-up time of 10.1 years. At the time of the study eighty nine percent of the eyes had normal vision (0.7 or better), 3% slight impairment of vision (0.6-0.3), 5% low vision (0.2-0.05) and 3% were blind. Visual field defects were mild in 78%, moderate in 13% and severe in 8% of the eyes. One eye (1%) had normal fields. In 8 patients the stage of the field defects was asymmetrical between the two eyes. All were able to read at least monocularly with glasses. No one was blind, retired early or professionally limited because of pigmentary glaucoma. Thirty-nine eyes were on topical treatment. Fifteen eyes had additionally been treated with laser trabeculoplasty when the glaucoma could not be stabilized with topical treatment combined with systemic acetazolamide. Further twenty eyes had undergone trabeculectomy, 18 of them when medical treatment had failed and 2 following LTP. The non-involved eye of a patient suffering from a monocular disease was without treatment. The mean intraocular pressure at the time of the diagnosis was 33.5 mmHg (SD 10.4 mmHg) and at the final visit 17.5 mmHg (SD 3.4 mmHg). Four eyes were operated for cataracts and one for retinal detachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750312 TI - Computerized patient record system for the glaucoma ward. AB - A system for computerized glaucoma patient record, developed from a data base called 'Advanced Revelation', is described. The record is made up from free text as well as from choices among listed alternatives. All data are stored on magnetic media and also printed out on paper in a well disposed and easily surveyable form. Apart from saving personnel and time in the clinical routine, the main advantages of the system is a powerful tool for clinical research. Data retrieval occurs on 'list', 'count', or 'sort' orders, facilitating retrospective studies. The system has been used for over a year at a glaucoma ward (Lund) to increasing satisfaction. PMID- 1750313 TI - Trabeculectomies. A long-term study. AB - This study comprises 277 primary open-angle glaucomas in 239 patients followed up to 10 years after trabeculectomy. Sixty-four per cent had capsular glaucoma and 36% simple glaucoma. The number of cases showing no progression of glaucoma damage and not needing additional medical therapy decreased slowly with time. Seventy-five per cent showed no progress after one year, 70% after 2 years, 57% after 5 years and 42% after 10 years. There was a significant trend that fewer capsular glaucomas progressed than simple glaucomas. High pressure levels before trabeculectomy did not indicate a bad prognosis. Cases with advanced or moderate glaucomatous damage seemed to have the same prognosis. Cataract was a common complication; a 50% reduction of preoperative visual acuity was found in 37% of eyes after 5 years of follow-up. PMID- 1750314 TI - Trabeculectomy with 5-fluorouracil. AB - The effect of subconjunctival injection of 5-fluorouracil (5-FU) after trabeculectomy was studied retrospectively in 205 eyes of 168 patients. A life table analysis of the surgical outcome was based on the type of glaucoma and age related differences, and a comparison was made with patients who had trabeculectomy without subconjunctival 5-FU. The success rate at 30 months after trabeculectomy with 5-FU therapy was considerably higher in primary open-angle glaucoma at 93.6% (72.7%), secondary glaucoma at 88.9% (72.4%), and refractory glaucoma at 72.2% (32.5%) with (or without) the use of ocular hypotensive drops when compared with historical control groups treated without 5-FU (60.0% (41.7%), 35.5% (24.0%), and 18.0% (8.0%), respectively). In patients aged over 70 years, no statistically significant improvement could be demonstrated with the use of 5 FU after trabeculectomy in primary open-angle glaucoma. Our study may provide data on the appropriate dosage and indications for the use of this drug after glaucoma surgery. PMID- 1750315 TI - Prevention of the rise in intraocular pressure following neodymium-YAG posterior capsulotomy using topical clonidine. AB - We studied the ability of topical clonidine, an alpha-agonist, to suppress the acute rise in intraocular pressure (IOP) following neodymium-YAG posterior capsulotomy (YPC). In a randomized controlled trial 63 eyes were pretreated with one drop of either 0.25% clonidine or saline 1 h before performing YPC and immediately following the procedure. The greatest IOP rise in the saline treated eyes occurred in the second hour after YPC, when the mean (+/- SD) IOP rose from a baseline pressure of 12.7 +/- 3.2 to 18.7 +/- 10.7 mmHg. In clonidine treated eyes, the IOP fell from a mean of 11.9 +/- 3.4 to 9 +/- 3.3 mmHg 2 h postoperatively. In the saline treated group 9 eyes (27%) developed an IOP rise greater than 10 mmHg. Clonidine proved to be highly effective in preventing the rise in IOP following YPC. PMID- 1750316 TI - Iris vasculopathy in exfoliation syndrome. An immunocytochemical study. AB - Samples of control iris tissue obtained from seven enucleated eyes and nine exfoliative iridectomy specimens were prepared for an immunocytochemical study of the matrix in the walls of iris vessels. The distribution of collagen types I, IV and laminin was studied in normal and exfoliative vessels. Laminin was an integral component of exfoliation material and was present mainly in the matrix of the outer surface of normal vascular cohort cells. The laminin content in the latter location was reduced in vessels in which exfoliation aggregates were not visible. Collagen type IV was absent from exfoliation material. While type I was present in the deposits, it was considered to represent a residue of native normal tissue. Exfoliation deposits appeared to stimulate the synthesis of collagen types I and IV at an early stage of the disease. PMID- 1750317 TI - Primary success with low vision aids in age-related macular degeneration. AB - The benefit obtained from various low vision aids (LVAs) was studied in 65 consecutive patients with atrophic (70.3%) or disciform (29.7%) age-related macular degeneration (ARMD). 13.8% were able to read newsprint with age-related reading correction under proper lighting conditions. The primary success achieved with LVAs was good, 91.4% of patients being able to read newsprint. In most cases a simple magnifier (52.3%), high-powered reading glasses (10.8%) or Fonda's glasses (12.8%) were sufficient. The magnification preferred was 5x or less in 25.6% and greater than 5x to 9x in 48.8%. Patients with disciform degeneration required higher magnification than those with atrophic degeneration. It is concluded that most patients with ARMD found low vision aids useful for reading purposes and that a simple optical device was sufficient to achieve reading vision. PMID- 1750318 TI - pH homeostasis in the frog retina: the role of Na+:HCO3- co-transport in the retinal pigment epithelium. AB - Transport of acid/base equivalents across the isolated frog retinal pigment epithelium (RPE) was studied by means of pH selective microelectrodes. Abrupt changes in retinal extracellular pH, from 7.40 to values between 6.66 and 7.66, were found to cause rapid changes in both intracellular pH and choroidal extracellular pH. The initial rates of these changes were reduced by more than 60%, when the cellular Na+:HCO3- co-transport system was inhibited by Na+ removal, or by administration of 1 mM SITS. It is concluded that RPE transcellular HCO3- transport changed in response to changes in retinal extracellular pH. If present in vivo these changes in RPE HCO3- transport would tend to stabilize retinal extracellular pH. It is suggested that cellular Na+:HCO3- cotransport plays a significant role for the retinal pH homeostasis. PMID- 1750319 TI - The postnatal development of the oscillatory potentials of the electroretinogram. III. Scotopic characteristics. AB - The postnatal development of the oscillatory potentials (OPs) of the rat electroretinogram (ERG) was studied during more extreme scotopic conditions. Enhancement of scotopic conditions did not facilitate any earlier appearance of the OPs, including the later ones, compared to previously studied less scotopic conditions. The oscillatory activity appeared at Days 12 to 15, and increased rapidly up to Day 17, which coincided with the major period of development of the photoreceptors. After the physiological opening of the eyelids there was a decline of the OPs. We propose that the decline of the oscillatory activity induced during more extreme scotopic conditions is related to early cell death in the distal retina and/or to developmental neuronal plasticity in the proximal retina. PMID- 1750320 TI - High-pass resolution perimetry and age-related loss of visual pathway neurons. AB - The normal, age-related decline of results of high-pass resolution perimetry (HRP) predicts a loss of approximately 9,000 retino-cortical neural channels per year of age, or about 1 channel each hour. Previously published counts of numbers of neurons in the optic nerve indicate a loss of approximately 5,000 neurons per year. The HRP results can be accounted for by postulating that neurons are lost at the same rate also in the geniculo-striate visual pathway. PMID- 1750321 TI - High-pass resolution perimetry in uncomplicated myopia. AB - Fifteen subjects (28 eyes) with uncomplicated myopia (3-9 D) were examined using high-pass resolution and Goldmann perimetry. In the central 30 degree field a slight increase was observed in mean resolution threshold significantly correlated to the degree of myopia. In the Goldmann visual fields threshold increase was observed in the area around the blind spot in eight subjects (10 eyes). In the resolution fields only one subject (one eye) showed a corresponding abnormality. PMID- 1750322 TI - Loss of visual function associated with microalbuminuria in diabetes mellitus: a pilot study. AB - Visual function loss has been documented in diabetes mellitus in relation to flicker and contrast. However, no direct correlation between the degree of loss in sensitivity and the level of retinopathy has been established. It has been suggested that such non-invasive psychophysical procedures actually reflect metabolic disturbances within the diabetic retina. This study investigates the possibility of whether early nephropathy demonstrated by microalbuminuria, is an indicator of microangiopathy which may be a cause of retinal disturbance leading to a loss of visual function. The visual function of a group of diabetics showing microalbuminuria was studied. Contrast and flicker threshold were measured and the results compared with those obtained with an age-matched control diabetic group. The procedures used effectively separated the two groups and raises the issue of incorporating psychophysics in retinal screening programmes. PMID- 1750323 TI - Does the lymph drainage from the head influence aqueous humour outflow and visual functions? AB - Effect of lymphoedema of the head on the central nervous system is known. Possible changes in intraocular pressure, tonogram, electroretinogram, visual functions and ophthalmologic state was studied in animal experiments and in patients following serious surgical impairment of the cervical lymph drainage. Lymph drainage from the orbit to the deep cervical lymphatics was established, while no ophthalmologic alteration was detected after surgery. PMID- 1750324 TI - Tear lysozyme levels in bacterial, fungal and viral corneal ulcers. AB - Low levels of tear lysozyme were observed in patients with infective corneal ulcers, when compared with controls. Lowest levels were seen in patients with bacterial corneal ulcers. The levels of tear lysozyme showed a corresponding decrease with the increase in Schirmer test values; meaning thereby, that in ocular conditions associated with increased rate of tear flow, the lysozyme content in tears tends to be low. PMID- 1750325 TI - A model for testing the mutagenicity of excimer laser radiation in ophthalmology. AB - Because excimer laser radiation is applied more and more in therapeutic and refractive corneal surgery, the possibility of mutagenic side effects of this treatment should be considered. A mutagenicity model is presented approximating closely the ophthalmological conditions when mutagenic effects are studied: Heparinized human blood is filled into the anterior chamber of an enucleated cow eye. After irradiation of the cornea with the excimer laser, the blood is removed and whole blood cultures are set up. Lymphocytes are stimulated, fixed during metaphase, and scored for chromatid and chromosome aberrations. First results obtained with this model after 248 nm laser irradiation (500 J, 277 mJ/cm2, 10 or 20 Hz) revealed no mutagenic effects. However, when the blood was exposed under the same physical conditions in a quartz chamber (positive control), statistically highly significant increases of the yields of chromatid aberrations were observed. PMID- 1750326 TI - Image analysis of conjunctival hyperemia. A personal computer based system. AB - An image analysis system that estimates conjunctival hyperemia is described. The system gives a good estimate of minor to moderate hyperemia in the conjunctiva, and is easy and fast to operate. PMID- 1750327 TI - Increased magnesium in aqueous humour from patients with senile cataract. AB - A previous observation of increased aqueous magnesium in eyes with senile cataract has been re-examined in a totally different material. The serum and aqueous level of calcium and magnesium from 34 patients with senile cataract were tested against comparable values from 4 patients with choroidal melanoma. In contrast to calcium, the magnesium aqueous/serum ratio was significantly higher in the cataract group. Possible explanations are suggested. PMID- 1750328 TI - Occult haemolacria in females. AB - A series of 125 healthy subjects were examined by the stix method (chemical response) for occult occurrence of blood in tears. Blood was found in 18% of fertile women, definitely most often in the menstrual phase (in 39% of 51 samples within the first week, reckoned from the first day of menstruation). The incidence was independent of use of the contraceptive pill. On the other hand, occult haemolacria was observed in no more than 7% (= 30) of pregnant women and in none at the menopause (N = 7). Among males the phenomenon was noticed in 8% (N = 24). Occult haemolacria in fertile women thus seems to be induced by hormones, whereas haemolacria most often is provoked by local factors (bacterial conjunctivitis, environmental damage, injuries). PMID- 1750329 TI - Visual acuity and refraction in type I diabetic patients aged 25-34 years. AB - Of the total population of 270 25- to 34-year-old insulin dependent diabetic patients with onset less than or equal to 30 years in the county of Fyn, Denmark, a sample of 138 was drawn for examination. Of the 138 examined patients, 4 (2.9%) were legally blind and 119 (86.2%) had good vision in both eyes. The cause of reduced vision was proliferative retinopathy in the majority of eyes. Refraction, measured objectively with a refractometer in cycloplegia and transformed to spherical equivalents, was -0.25 D or more myopic in approx. 50% of eyes. Correlation analyses did not demonstrate significant association between refraction, and duration of diabetes or Hb-A1c. PMID- 1750330 TI - Recurrent corneal epithelial erosions in Alport's syndrome. AB - Alport's syndrome is a heritable disorder of uncertain aetiology characterized by nephritis, sensorineural deafness and ocular abnormalities. Bilateral corneal epithelial erosions are a previously unreported finding which support the hypothesis that Alport's syndrome is a disorder of selected basement membranes. PMID- 1750331 TI - Acute glaucoma in the presence of a patent neodymium: YAG laser iridotomy. PMID- 1750332 TI - Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test. AB - The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores. PMID- 1750333 TI - Neonatal macrosomia and hypoglycaemia in children of mothers with insulin-treated gestational diabetes mellitus. AB - All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Orebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight greater than 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose less than 1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia. PMID- 1750334 TI - Studies on adherence and outer membrane protein of enteropathogenic Escherichia coli 0127: H6 and their related plasmids. AB - The following characteristics were found in 20 epidemic strains of enteropathogenic Escherichia coli (EPEC) 0127: H6 isolated from an outbreak of neonatal diarrhea: 1) Absent Vero toxin production; 2) No potential for invasiveness; 3) Possession of 1.5 and 60 Md plasmid identical restriction digest and outer membrane protein (OMP) patterns; 4) Ability of localized adherence to HEp-2, HeLa and FL cells; 5) Capability to cause diarrhea in rabbits with destruction of the ileal microvilli at the areas of bacterial adherence. After elimination of the 60 Md plasmid from EPEC 0127: H6 the 45 and 82 Kd OMPs of the parent strain were lost. These plasmid-cured strains became non-adherent to HEp 2, HeLa and FL cells, and unable to cause diarrhea in rabbits. These results suggest that the pathogenic mechanism of EPEC 0127: H6 induced diarrhea may be related to the genes on a 60 Md plasmid expressed as 45 and 82 Kd OMPs which cause localized adherence to epithelial cells and destruction of ileal microvilli. This damage leads to a marked reduction in absorptive surface area, resulting in diarrhea. PMID- 1750335 TI - The treatment of persistent diarrhoea and malnutrition: long-term effects of in patient rehabilitation. AB - This study aimed to characterise the clinical condition of Gambian children presenting with persistent diarrhoea and severe protein energy malnutrition and to evaluate the effects of short term in-patient treatment in terms of long-term outcome. Twenty-two children (aged 6 to 36 months) with persistent diarrhoea (greater than or equal to four loose stools/day for more than two weeks) and severe malnutrition (weight-for-height less than 75% of the National Center for Health Statistics median value) were assessed prior to in-patient treatment for three weeks with antibiotics and high nutrient-density milk. Initial assessment included biochemical and immunological status together with stool microbiology. Criteria for discharge--cessation of diarrhoea for five consecutive days and steady weight gain--were met in all subjects within four weeks. Progress was assessed clinically and anthropometrically at weekly intervals and 6 and 12 months following discharge. Results showed a steady improvement in growth during the period of in-patient treatment. Continuing improvement in weight-for-age and mid-upper arm circumference was observed after 6 and 12 months and weight-for height continued to improve up to 6 months but fell back by 12 months. This study has demonstrated that, in the treatment of persistent diarrhoea in the tropics, relatively short periods of in-patient rehabilitation, whilst leading to a resolution of diarrhoeal symptoms and weight gain in the short term, do not lead to complete recovery. Persistent diarrhoea and malnutrition are likely to recur when the child returns to his village.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750336 TI - Types of fluid disorder in children with bacterial meningitis. AB - As part of a prospective study of children with bacterial meningitis we analyzed in 36 patients of our hospital the fluid balance on admission and during the first three days of treatment. On admission 10 of them (28%) had inappropriate antidiuretic hormone secretion SIADH, 10 (28%) hypo-osmolal and 10 (28%) iso osmolal contraction. Six patients (17%) had no clear fluid disorder. The patients with SIADH had significantly lower mean serum NA+ (127 vs. 132 mEq/l, p less than 0.01) and higher mean urine Na+ (111 vs. 26 mEq/l, p less than 0.01) concentration as well as higher mean urinary Na+/K+ ratio (2.23 vs. 0.365, p less than 0.005) than the patients with hypo-osmolal contraction. They also tended to be younger and have a shorter history of fever. The patients with SIADH had a less strict fluid restriction than the patients with hypo-osmolal contraction, and their fluid balance normalized more slowly. Our findings support initial water restriction for all children with bacterial meningitis. PMID- 1750337 TI - Immunoglobulin and complement studies in children with Schonlein-Henoch Syndrome and other vasculitic diseases. AB - In 35 children with Schonlein-Henoch Syndrome (SHS) serum IgG, IgM, and IgA concentrations were increased in 15%, 21%, and 44% of cases, respectively. Seven children with other vasculitic syndromes (VS) had normal serum Ig concentrations. Serum concentration of IgG subclass IgG1 was increased in 72% of children with SHS and 57% with VS. In SHS this was related to the presence of arthritis, but inversely related to nephritic symptoms. Only a few children had IgG subclasses IgG2, IgG3, or IgG4 concentrations outside the normal ranges. Platelet associated Ig (PAIg) was found in 75% of children with SHS or VS. In SHS the identification of increased amounts of PAIgG was related to the presence of nephritis. The serum concentration of properdin, a component of the alternative complement system, was reduced in 21% of children with SHS. This was related to the presence of abdominal symptoms or nephritis. No cases of retinal vasculitis was observed, but 4 of 22 children with SHS had punctuate retinal haemorrhages. SHS and VS may be clinical variations of the same syndrome. The immunological aspects indicate a close relationship with autoimmune diseases. PMID- 1750338 TI - The natural history of screening detected IgA glomerulonephritis in children. AB - The clinical course of 43 children with IgA glomerulonephritis detected by mass urine screening was followed for a mean period of 8.1 years. Histological findings were graded according to the severity of glomerular and tubulointerstitial lesions. There was no correlation in the severity of histological grade and clinical outcome between subjects with microscopic hematuria and those with microscopic hematuria and proteinuria nor between those with and without one or more episodes of macroscopic hematuria during the follow up period. None of the 35 children with proteinuria less than or equal to 1 g/m2/day had severe histological findings or developed renal impairment. In contrast, the 8 children with proteinuria greater than 1 g/m2/day had moderate and severe histological findings. Four of these 8 children developed hypertension or renal insufficiency during the follow-up period. Our study indicates that the outcome of screening detected IgA glomerulonephritis in children correlates with the level of proteinuria and the severity of renal pathology. PMID- 1750339 TI - Psychological and respiratory physiological effects of a physical exercise programme on boys with severe asthma. AB - Ten boys 9-12 years of age with severe perennial asthma participated in a physical exercise programme lasting 8 months. Pulmonary function and psychological tests were performed before training, immediately after, and one year after the end of the exercise programme. Static lung volumes, flow-volume variables and histamine tolerance were used as indicators of pulmonary function. Ego structure, body image, social development and concentration capacity were used as indicators of personality development. Before the study, the group had high FRC (p less than 0.05) and RV (p less than 0.001), low FEV1, MEF50 and MEF25 (all p less than 0.001) and low histamine tolerance. They showed marked disturbances in their personality development with low scores in psychological variables. During the training period, MEF50 and MEF25 increased slightly (p less than 0.01). Marked improvement was observed in all psychological variables (p less than 0.001). The positive effects remained during the following year. The marked and lasting improvement in personality development was regarded as an essential factor behind the more modest positive clinical and pulmonary function changes. The results emphasize the importance of including exercise programmes in the treatment of children with asthma. PMID- 1750340 TI - Epidemiology of absence epilepsy. III. Clinical aspects. AB - Absence epilepsy was studied in a Swedish population, aged 0-15 years, in 1978 1982. Cases were selected by electroencephalographic criteria. In the 134 children with 3 Hz spike-and-wave discharges, 97 (72.4%) had absences alone or in combination with generalized tonic-clonic seizures (grand mal): 56 had absences alone, 31 absences followed by grand mal, and 10 started with initial grand mal. Two distinct groups could be discerned: 1) childhood absence epilepsy: onset before the age of 12, with a quick response to therapy, little or no risk of grand mal, and a high remission rate; 2) juvenile absence epilepsy: onset at the age of 12 or later, a very high risk of grand mal, and usually a good response to therapy, but a high risk of relapses at withdrawal. This classification of absence epilepsy into subgroups may be useful for prognostic guidelines. PMID- 1750341 TI - Nose tapping test inducing a generalized flexor spasm: a hallmark of hyperexplexia. AB - The present report describes a benign disorder of neonates or young infants presenting with generalized hypertonicity accompanied by brisk muscle stretch reflexes, intermittent clonus, and exaggerated startle response. This condition is termed hyperexplexia, and may be either familial or sporadic. Two affected families are reported: Two sisters and their mother are involved in the first family; in the second family, where the parents are asymptomatic first degree cousins, all three siblings suffer from hyperexplexia of various severity. Nose tapping in infants of affected families induced a uniform reaction of facial twitching accompanied by head extension, and a generalized flexor spasm, all of which may be a hallmark of hyperexplexia. Severely hypertonic infants were treated with small doses of benzodiazepines and improved markedly, all becoming asymptomatic by two years of age. Unnecessary investigation and treatment may be avoided by sufficient awareness of possible hyperexplexia. PMID- 1750342 TI - School readiness and CNS maturity: relation to psychophysical and psychosocial development and to early school achievement. AB - In randomly selected schools 113 girls and 102 boys were subjected to a School Readiness (SR) test and to a Complex Reaction Time (CRT) measurement at the age of 7. Their psychophysical development, social adjustment and school achievement were assessed by teachers and by means of self-ratings during the first 3 school years. The developmental outcome of the children seemed principally related to CNS-maturity as measured by CRT, and not to the SR test scores. A CNS dysfunction, indicated by slow CRT, seemed to be an essential handicap during the early school years, impairing particularly the boys' language and motor development and their school achievement and causing feelings of inferiority. This handicap, which is mainly a developmental delay, should thus be taken into consideration when assessing school maturity. Early detection of this handicap might enable us to take preventive measures with regard to these children. PMID- 1750343 TI - Product-related home accidents in children. A survey of 1590 accidents. AB - In a well defined geographical area a total of 1590 accidents related to home products in children 0-15 years of age were prospectively registered. The incidence of product-related accidents was 279 per 10,000 children per year. A higher incidence in boys and a decreasing incidence of accidents with age was found. The most common localization of lesions was upper extremities 41% and face and skull 30%. In children 0-4 years of age household and child furniture, constructional features of the house and corrosives, hot liquids and heating equipment were the most common products causing accidents, whereas in children 5 15 years of age playthings and sports equipment as well as constructional features of the house were involved in a higher percentage of accidents. PMID- 1750344 TI - Is cow's milk protein sensitive enteropathy a cell mediated immunological phenomenon? PMID- 1750345 TI - Defective regulation of electrolyte and protein secretion in submandibular saliva of cystic fibrosis patients. PMID- 1750346 TI - Osteocalcin cord plasma levels: influence of perinatal factors. PMID- 1750347 TI - The responses of plasma ionised calcium and intact parathyrin to calcium supplementation in preterm infants. PMID- 1750348 TI - Frequent past exposure to adenovirus 12 in coeliac disease. PMID- 1750349 TI - Brain abscess in glycogen storage disease type Ib. AB - Neutropenia, neutrophil dysfunction, and recurrent infections are important manifestations of glycogen storage disease type Ib. We report here a child who has had adequate metabolic control, but developed brain abscess, an infection not previously described in this disease. This case provides further evidence that the neutrophil anomaly is related to the basic enzyme defect, not secondary to the metabolic derangement. PMID- 1750350 TI - Faecal incontinence due to perianal cellulitis. AB - A 4-year-old boy presented with a 6-week history of painful defaecation and faecal incontinence due to streptococcal perianal cellulitis. After treatment with a 10-day course of oral penicillin his symptoms had fully resolved. Early diagnosis and treatment of this under-recognised condition is essential. PMID- 1750351 TI - Imerslund-Grasbeck syndrome in a Saudi family. AB - Imerslund-Grasbeck syndrome, an autosomal recessive trait of defective uptake of intrinsic factor-vitamin B12 complex by terminal ileum, is described in a Saudi family (two siblings and their first cousin). This rare disease has previously been reported only in Northern Europe and North African Jewish ethnic groups. PMID- 1750352 TI - Atypical allergic colitis in preterm infants. AB - Two atypical cases of colitis due to cow's milk protein intolerance (CMPI) are reported, affecting preterm infants. One developed a toxic dilatation of the colon and responded well to a casein hydrolysate based feed. The second presented insidiously and failed to tolerate a casein hydrolysate, but responded well to a chicken-based modular feed. PMID- 1750353 TI - Design and performance of blanket heat shields for neonates. AB - BACKGROUND: Several designs of plastic blanket heat shields are in use. This study was done to compare different designs for their efficiency in reducing heat loss. METHODS: Four heat shield designs were tested by sequentially covering each of 14 infants (wt. 640-2,030 g) cared for under radiant warmers. The power consumption of the radiant warmers was measured as a surrogate for heat loss. All designs were tested for a total of 20 min on all infants. Results were calculated as percent change in power consumption from shield to shield. The most efficient design was further modified and evaluated in another group of 14 infants (wt. 700 1,180 g). RESULTS: The relative reductions in power consumption were: no shield (control) -0%, a plastic foil over the side rails: -17%, a single layer close to the infant but excluding the head: -34%, the same as double layer -37% and the most efficient one, a single layer covering the whole infant -42%. A modification of this design, tested in the second group of infants, reduced power consumption by 13% (95% CI -5.9/-19.7), (p less than 0.004) when compared to the single layer covering the whole infant. It was tucked under the connecting tubes to the ventilator. It also reduced the risk for displacement and allowed for the endotracheal tube to be suctioned without removing the blanket. CONCLUSION: Modifications of the design of heat shield blankets for infants resulted in significant increases in efficiency. PMID- 1750354 TI - Periodic variations in skin perfusion in full-term and preterm neonates using laser Doppler technique. AB - In 37 full-term and preterm infants periodic oscillations of skin blood flux were studied by means of laser Doppler technique during the first week of life. The development of rhythmic oscillations of skin blood flux was similar in all infants. On the first postnatal day rhythmic oscillations were present in the heel skin of all full-term and preterm infants, but were rarely observed in the back and thigh skin. These flux motion patterns were not influenced by small changes in skin temperature. On day 4 rhythmic oscillations became predominant in all body regions. The oscillation frequencies of blood flux in the back, thigh and heel skin of full-term neonates reached the lower range of adult values at the end of the first postnatal week, whereas the oscillation frequencies in the preterm infants were still below the range of full-term neonates. PMID- 1750355 TI - Glutathione peroxidase and glutathione S-transferase, class alpha, in rat intestine. Immunohistochemical and immunoblotting studies on changes in expression of these antilipoperoxidative enzymes during normal development. AB - Glutathione peroxidase (GSH-PO) and glutathione S-transferase (GST), class alpha, showing GSH-PO-like enzymatic activity, were localized immunohistochemically in frozen sections of rat intestine in order to elucidate changes in the expression of these antilipoperoxidative enzymes during normal development. The direct immunoperoxidase method was performed using specific rabbit antibodies (Fab fragments) against the enzymes purified from rat liver. Immunoreactive GSH-PO and GST-alpha were demonstrated in the intestinal villous epithelial cells. In the duodenum, GSH-PO was positive during the period from 19 days of gestation to 1 week after birth, while GST-alpha was negative during this period. Two weeks after birth, positivity for GST-alpha appeared, and GSH-PO became undetectable. In the ileum, both of the enzymes were observed until 2 weeks of age, but after weaning their expression disappeared. These immunohistochemical findings were confirmed by immunoblot analysis using intestinal tissue extracts. To evaluate environmental effects on the expression of these enzymes, germ-free animals, common bile duct-ligated rats, and Hank's solution-fed infant rats were prepared. No remarkable alterations in the immunohistochemical localization pattern were observed. Since the switching of enzyme expression around the time of weaning was not influenced by these experimentally induced environmental conditions, it appears that these enzymatic changes are genetically predetermined. PMID- 1750356 TI - Immunohistochemical observation of recovery of the periarteriolar lymphoid sheath, lymph follicle and marginal zone in the 60Co-irradiated spleen of rats. AB - After 60Co irradiation of rat spleen, the most severe damage was found initially in the lymph follicles (LFs); lymphocytes were decreased in number in the periarteriolar lymphoid sheath (PALS), and almost completely depleted in the marginal zone (MZ). Recovery was observed first in the PALS, followed by the LFs, and finally the MZ. From the results of immunohistochemistry, the process of recovery was assumed to involve migration of T and B lymphocytes along the arterioles from the area surrounding the terminal arteriole at the end of the PALS into the central part of the PALS and into the LF. Peripheral blood IgM+, IgD- B lymphocytes, known to be MZ precursor cells, flowed from the follicular artery to settle in the MZ. Furthermore, recovery of the PALS prior to the LFs was suggested to be essential for lymphocyte migration to the LFs. PMID- 1750357 TI - Quantitative study of neurofibrillary tangles in subdivisions of the hippocampus. CA2 as a special area in normal aging and senile dementia of the Alzheimer type. AB - The frequency of neurofibrillary tangles (NFTs) in relation to aging was examined in five regions of the hippocampus of 139 normal controls (60 to 106 years) and 14 patients with senile dementia of the Alzheimer type (SDAT). The regions were CA4, CA3, CA2 and CA1, the latter being subdivided into CA1a (the region near CA2) and CA1b (the region near the subiculum). Only CA2 showed no correlation of NFTs with normal aging. CA2 in SDAT was the site most vulnerable to NFT formation. Therefore, it is considered that CA2 is a special region in both normal aging and SDAT. CA1 was characterized by the early appearance of large amounts of NFT, and was the most reliable marker of senile change related to aging. Like CA1, both CA3 and CA4 showed an increase of NFTs with normal aging, but their aging process was far less marked. In addition, statistical analysis based on a "normal" distribution was considered to be unsuitable for quantitative study of senile change, because no histogram of NFTs in any subdivisions for any age showed such a distribution. PMID- 1750358 TI - Granulomatous arteritis with massive eosinophilic leukocyte infiltration and transient peripheral eosinophilia subsequent to transarterial embolization therapy with a gelatin sponge. AB - A 38-year-old man presented with a cavernous hemangioma in the liver. Transarterial embolization (TAE) using a gelatin sponge was carried out 14 days prior to surgical resection of the tumor. Granulomatous arteritis with massive infiltration by eosinophilic leukocytes and histiocytes was present at the periphery of the hemangioma, and transient eosinophilia in the peripheral blood occurred six days after resection. Granulomatous arteritis was evident in medium sized arteries and there was narrowing or occlusion of the vascular lumen. In the granulomatous cellular infiltrates in the arteries, giant cells of the foreign body type were numerous. An eosinophilic substance differing from fibrin was present in some of the vascular lumina. As this showed staining for collagen, it was considered likely to be fragments of the gelatin sponge. The patient had no symptoms of fever, chills or general fatigue. The clinical course and pathologic findings suggest a causative role of the gelatin sponge in this case of granulomatous arteritis. Vascular change, a rare complication of TAE therapy, may be induced by a hypersensitivity reaction against the intra-arterial gelatin sponge. PMID- 1750359 TI - Primary malignant lymphoma of the rectum with diagnostic problems. Report of two cases with an analysis of gene rearrangement. AB - We present two similar cases of rectal B-cell lymphoma with diagnostic problems. Grossly, both tumors appeared as a well demarcated polypoid mass with eroded mucosa. In spite of their histologic resemblance to reactive lymphoid hyperplasia, including the presence of lymph follicles, fibrosis and polyclonal plasma cells, both cases were diagnosed as malignant lymphoma of low-grade malignancy because of the full-thickness involvement of the rectum with diffusely infiltrated small or medium-sized lymphoid cells showing rare mitoses. In one case, clonal proliferation of differentiated B cells was demonstrated by analysis of gene rearrangement. Therapeutic problems related to low-grade malignant lymphoma in the rectum are also discussed. PMID- 1750360 TI - Abortion of a sow caused by Pasteurella aerogenes. AB - Three strains of the Pasteurella aerogenes complex were isolated as sole pathogens from aborted fetuses of a sow aborted at the 12th week of gestation on a farm of 600 sows. Gross pathology showed no characteristic lesions. The isolates were biochemically identical and resembled P. pneumotropica on the basis of their strong indole and urease positivity but they produced gas, were ornithine decarboxylase negative and fermented mannitol but not trehalose. Only a few differences were apparent in biochemical characteristics between the isolated strains and P. aerogenes. They differed from the type strain of P. aerogenes in ornithine decarboxylase activity, indole production and lactose and mannitol fermentation; however, such strains do occur within this heterogeneous species. At the time of abortion the antibody titre of the aborted sow was 1 in 16 when examined with live bacterial suspension and 1 in 128 if boiled antigen was used. Similar strains could not be isolated from the vaginas of aborted sows or pregnant and newly farrowed sows in the same group. The bacteriological, serological and histological findings support the opinion of other workers on the occasional pathogenic nature of P. aerogenes. PMID- 1750361 TI - Suitability of lactate dehydrogenase activity and somatic cell counts of milk for detection of subclinical mastitis in Merino ewes (short communication). AB - The relationship between somatic cell counts (SCC) and LDH activity in milk was examined in Turkey to find out the suitability of these variables for early detection of subclinical mastitis in Merino ewes. A significant positive correlation was found between LDH activity and SCC in ewes' milk. LDH activity in milk samples appeared to be a sensitive and specific indicator of subclinical mastitis in ewes: it was significantly higher in milk from inflamed (mastitic) udders than in normal milk. PMID- 1750362 TI - Goat serum, a substitute of bovine serum in cultivation of Babesia bovis. AB - Babesia bovis (a Mexican isolate) was cultivated in MASP culture system using goat serum in various concentrations as substitute of bovine serum. It was observed that 20% goat serum + 20% bovine serum + 60% Parker's medium 199 supported the growth of the parasite, which was maintained in this medium through 8 subcultures. The soluble exoantigen (vaccine) present in the culture supernatant is to be quantified and tested in vitro. Goat serum from slaughterhouses may be utilized for in vitro cultivation of the parasite and, expectedly, production of vaccine. This study may prove to be useful in reducing the cost of vaccine at least in tropical countries. PMID- 1750363 TI - Changes induced in newborn piglets by the trichothecene toxin T-2. AB - Three pregnant sows, being in the last quarter of gestation, were used in an experiment to study the changes induced in newborn piglets by T-2 toxin. One sow was used as control (C). The other two received 24 mg (sow A) and 6 mg (sow B) T 2 toxin, respectively, mixed in the feed, daily, up to the time of farrowing. The piglets of sow A became ill by 48-72 h after birth, while the litters of sow B and C remained healthy. The clinical symptoms included faintness, diarrhoea, decreased blood glucose level, and collapse followed by death. The milk and urine of sow A and the stomach contents of affected and dead piglets contained T-2 toxin and its metabolites. Pathological changes seen at necropsy included acute enteritis, degeneration of the liver and kidneys, and oedema of the mesentery. The stomach was filled with clotted milk. Histopathological and electron microscopic findings consisted of reduced glycogen content and pathological simple fatty infiltration of the liver cells, lymphocyte depletion and necrosis in the lymphoid follicles of the intestinal mucosa, atrophy of the thymic cortex, and hyperfunction of the adrenal and thyroid glands compared to the control. PMID- 1750364 TI - Effect of treatment with Prolan or with a GnRH superactive analog on the sexual function of sows after weaning. AB - On a large, closed pig farm using artificial insemination (AI), 29 sows were treated with Prolan S-ol injection (Bayer, FRG) and 31 sows with a GnRH superactive analog (Ovurelin, D-Phe6-GnRH-EA, Reanal, Hungary) 48 h after weaning. The effect of treatment on the sows' sexual function was monitored by serum progesterone radioimmunoassay (RIA). The conception rate in the control group (36 sows) was 69.4%. In the groups treated with Prolan and Ovurelin it was 79.3 and 71%, respectively. The use of Prolan S-ol injection markedly reduced the number of acyclic sows and of those having an irregular oestrous cycle. Treatment with the GnRH analog inhibited the manifestation of weaning-induced heat; subsequently, however, it induced a regular cycle in 30 out of the 31 sows treated. PMID- 1750365 TI - Effect of volatile fatty acid infusion on blood plasma free amino acid profiles in growing lambs. AB - Five ram lambs (average body mass: 25 kg) were given, through a catheter inserted into the left ruminal vein, a total of 28.8 mM sodium acetate, 14.4 mM sodium propionate and 4.8 mM sodium butyrate per kg body mass as a 2-hour infusion. During and at 0, 1, 2, 4, 6, 10 and 24 h after the infusion blood samples were taken from the jugular vein and the blood plasma was assayed for free amino acid (FAA) and immunoreactive insulin (IRI) concentrations. Volatile fatty acid (VFA) infusion significantly decreased the blood plasma concentrations of all FAA but cystine. The lowest FAA concentrations were measured in plasma samples taken at the end of the 2-h infusion. Subsequently the level of all amino acids rose and by 24 h after the infusion the blood plasma concentration of all FAA came close to the preinfusion value. The largest differences were observed in the concentration of glutamate, glycine, leucine and isoleucine. In contrast to FAA, IRI concentration was increased significantly (almost fivefold) by VFA infusion. By 10 h after the infusion IRI concentration returned to the initial level. The results reported here indicate that energy supply given in the form of VFA infusion significantly affects blood plasma FAA profiles, supposedly as a result of changes induced in protein synthesis in tissues. Insulin presumably plays a role in the regulation of these changes. PMID- 1750366 TI - Blood pH, plasma carotene, vitamin A, albumin and globulin concentrations in newborn calves and in dams during the first three days of the postnatal period. AB - Blood pH, total plasma carotene, plasma vitamin A fractions and some plasma proteins were determined in newborn calves (n = 38) and their dams. Calves were assigned to one of two groups according to their blood pH immediately after birth: group 1 (normal) with pH above 7.2 (n = 27) and group 2 (slightly acidotic) with pH 7.0 to 7.2 (n = 11). The difference between the neonatal blood pH values of the two groups immediately post partum disappeared 24 h after birth. The blood pH of the dams was normal. The extremely low plasma carotene concentration (group 1: 32.7 micrograms/l; group 2:20.5 micrograms/l) and the low plasma globulin fractions (group 1:19.6 g/l; group 2:19.2 g/l) immediately after birth were elevated by the intake of colostrum. There was no significant change in plasma vitamin A fractions (retinol, retinyl ester) during the early postnatal period (3 days post partum) in newborn calves. The acid-base balance of newborn calves does not have any influence on the physiological alterations of plasma vitamin A, carotene and some plasma proteins during the first three days of life. PMID- 1750367 TI - Lipid composition of pulmonary surfactant in breeding foxes with cardiopulmonary insufficiency. AB - The lipid composition of the pulmonary surfactant of breeding foxes was examined. The surfactant isolated from healthy polar and common foxes did not show significant strain differences in lipid composition. On the other hand, in the surfactant isolated from the lung of common foxes that died with the symptoms of cardiopulmonary insufficiency the quantity of phosphatidylcholine and phosphatidylglycerol was lower and that of sphingomyelin and lysophosphoglycerides was higher than in the surfactants prepared from healthy animals. Moreover, in the phosphatidylcholine and phosphatidylglycerol fractions of the surfactant isolated from the diseased animals the level of palmitic acid was significantly lower. PMID- 1750368 TI - Effect of some electrolytes on in vitro rumen microbial protein synthesis in buffaloes. AB - In vitro studies were carried out to examine the effect of MnCl2, MgCl2, CoCl2 and CaCl2 on protein synthesis by rumen microorganisms obtained from fistulated buffalo calves (Bubalus bubalis). The concentration of the electrolytes in stained rumen fluid (SRF) ranged from 1 to 20, 1 to 20, 0.25 to 5 and 1 to 20 mM, respectively. MnCl2 (15 mM), MgCl2 (10 mM), CoCl2 (2.5 mM) and CaCl2 (20 mM) increased the protein content in the incubation mixture (IM) by 501, 230.8, 537.6 and 84% and the per cent incorporation of 35S from (NH4)2 35SO4 into microbial protein by 125.6, 108.5, 113.4 and 40.3, respectively, over the control values, when the incubation lasted 8 h. The NH3-N content in IM decreased by 8, 14, 43 and 16% when 10 mM MnCl2, 20 mM MgCl2, 1 mM CoCl2 and 1 mM CaCl2, respectively, was added and the incubation lasted 6 h. The reasons for increased protein biosynthesis by rumen microorganisms in the presence of the above electrolytes are discussed. PMID- 1750369 TI - The school placement revolution. PMID- 1750370 TI - Teacher competency exams. PMID- 1750371 TI - Conservation and metaphor acquisition in hearing-impaired children. Some relationships with communication mode, hearing acuity, schooling, and age. AB - This study focused on conservation and metaphor acquisition in 35 hearing impaired children who used different modes of communication and who spanned a wide age range. Children who used either cued speech or oral-aural communication modes were tested at two different school sites. Relationships were determined between the dependent variables, conservation and metaphor, and the independent variables of age, degree of hearing loss, years of schooling, and mode of communication. Findings revealed a significant positive relationship between conservation and metaphor in both communication modes. Significant relationships between age and metaphor and between age and conservation were also found, suggesting that experience plays an important role in understanding both of them. Neither conservation nor metaphor was significantly related to either degree of hearing loss or communication mode. The conservation order of acquisition was number (91%), weight (60%), volume (50%), and liquid (46%). Suggestions for teachers based on the findings are presented. PMID- 1750372 TI - ASL and the family system. AB - This paper examines some of the sociological implications of poor interaction on families in which one of the members is deaf. When a family systems perspective is used, once a child is diagnosed as deaf the family is no longer considered "hearing"; the parents may be hearing, the other children may be, but the family system becomes "hearing and deaf." By viewing this as a hearing/deaf problem, it becomes clear that no adequate solution can be found without the participation of deaf adults and the benefit of their perspectives and insights. We suggest that attention be directed toward neutralizing the effects of the stigma associated with deafness so that American Sign Language can become a pivotal tool for facilitating functional symbolic interaction in hearing/deaf families. PMID- 1750373 TI - Improving the career decisions of deaf seniors in residential and day high schools. AB - Career development interventions can have positive effects on the career decisions that deaf seniors make before graduating from high school. Interviews with 189 seniors from 16 residential and day high schools revealed their career decisions and their experiences with career development activities. School staff evaluated the seniors' career decisions, career decision-making skills, and probable post-high school placements. The results indicated that seniors who had vocational training were more knowledgeable about their vocational aptitudes than were seniors who had no vocational training. Seniors with vocational training were also more likely to have considered other careers prior to making career decisions. Seniors who had received career counseling were more knowledgeable than those who had not about the skills needed to enter their chosen careers and were more interested in their career choices. More importantly, the amount of interest in one's career choice was determined to be related to ratings of motivation, readiness, and prospects for completing the postsecondary placement. The implications of these results are discussed below for professionals in education and rehabilitation. PMID- 1750374 TI - A national profile of school-based transition programs for deaf adolescents. AB - In this study, the transition programs of 326 secondary educational programs for deaf and severely hearing-impaired adolescents were surveyed. Three types of programs were surveyed: residential, mainstream, and "other" (a combination of the first two programs). Sixty-four items depicting desirable transition characteristics were included in the survey, and each item was rated by the programs on a value scale and an implementation scale. Analyses of variance were calculated to determine if there were statistically significant differences among the three program types for each individual survey item on the two rating scales. Based on the data, it appears that the residential schools had higher implementation rates than the mainstream and other programs. All three respondent groups valued the transition items more than they had implemented them (i.e., the value scores were higher than the implementation scores). The data point out the need for researchers and educators to develop and implement more effective transition programs for deaf and severely hearing-impaired students. PMID- 1750375 TI - When the same is different. A comparison of the information processing strategies of deaf and hearing people. AB - In this study, the information processing strategies of Gallaudet University students who are profoundly and prelingually deaf were evaluated. The subjects demonstrated the highest levels of recognition to the left and right of the fixation point, often referred to as a reading strategy when found in hearing people. Additionally, they demonstrated higher levels of recognition at positions in the top right quadrant of the display, a pattern not found in hearing people. A main effect was found: subjects whose primary and secondary school backgrounds were oral and manual combined had significantly higher levels of recognition overall than did subjects from oral-only educational backgrounds. Differences in background did not interact with strategy use in this study. These findings lead to the conclusion that the information processing strategies of deaf people need to be evaluated closely before general conclusions can be made. Alternative means for evaluating these types of findings are suggested. PMID- 1750376 TI - Self-concept in hearing and prelingual, profoundly deaf students. A comparison of teachers' perceptions. AB - A self-concept measure was administered to a group of 68 deaf students aged 8-19 years and a comparison group of 68 hearing students. Teachers for both of the groups completed observer reports of self-concept. Although tentative, the findings indicate that hearing teachers' perceptions of students' self-concepts are in closer agreement for hearing students than they are for deaf students. At the same time, the results show that deaf students do not appear markedly different from hearing students in their own reports of self-concept. PMID- 1750377 TI - Family-centered early intervention. The perceptions of professionals. AB - This paper, based on a nationwide survey, examines the attitudes and opinions of professionals regarding parent-professional involvement in the planning and implementation of goals and services for hearing-impaired infants and toddlers and their families. The implications of the findings are discussed as they pertain to PL 99-457, the new federal mandate for services to young children with special needs and their families. PMID- 1750378 TI - New aspects of the morphology and function of the human hip joint ligaments. AB - The capsular ligaments of the human hip joint were submitted to exact morphological analysis, and they proved to be multiple and numerous. We have described various ligamentous systems and their interconnections, and have suggested new terminologies and systematics. The ligaments were subjected to functional analysis by means of measuring strips to determine the positions in which the ligaments are taut. The ligament systems were all found to serve a restrictive function, and various parts of the apparatus restricted all possible movements in the hip joint. Extension is restricted by the medial iliofemoral complex, abduction by the pubofemoral ligament, and adduction by the posterior coxal ligaments and by the superior ischiofemoral ligament. Flexion is restricted by the inferior ischiofemoral ligaments, inward rotation by the superior ischiofemoral ligament, and outward rotation by the lateral iliofemoral complex. Only the ligament of the femoral head is unable to exert a restricting function, despite reaching a state of tension in extreme adduction. PMID- 1750379 TI - Generation of color composites for enhanced tissue differentiation in magnetic resonance imaging of the brain. AB - Currently, the diagnostic interpretation of magnetic resonance (MR) images requires that radiologists integrate specific tissue contrast information from several different images obtained at the same anatomic slice position. Each of these images has its own unique tissue contrast patterns which are based on the image acquisition parameters (pulse sequence) selected. The complex contrast patterns observable in these images reflect the inherent biophysical characteristics of the tissues and fluids present in the imaged section. In an effort to increase the diagnostic accuracy and efficiency of MR image interpretation, we have generated color composite images from quantitatively analyzed achromatic MR images of the brain, obtained while utilizing different pulse sequences. By using a DEC MicroVAX II computer with Interactive Digital Language (IDL), this color display method has been applied to images obtained from General Electric Signa and Siemens Magnatom imagers. For this study, our image sets included T1-weighted, T2-weighted, and proton density spin echo sequences as well as both high and low flip angle gradient echo sequences. Advantages of our color composite methods, in contrast to many other image processing techniques that have been described, are that minimal information is lost, computer misclassification of tissues is avoided, and the conspicuity of specific tissues is enhanced. Furthermore, with this method it is possible to produce composite images whose color renditions approach a natural anatomic tissue appearance. Availability of these color composites to radiologists may improve the efficiency and accuracy of the diagnostic interpretation of MR images. PMID- 1750380 TI - Electron microscopic and histochemical studies of the mononuclear osteoclast of the mouse. AB - Osteoclasts collected from the long bones of mice were cultured on dentin slices. To identify osteoclasts, the tartrate-resistant acid phosphatase (TRACPase) activity of cultured cells was histochemically examined by the azo dye method. The TRACPase-positive cells could be distinguished from other cells by light microscopy. The cells were sectioned by alternating semithin and ultrathin sections to observe their ultrastructure and three-dimensional structure. TRACPase activity was detected both in multi-nucleated osteoclasts and in mononuclear cells. Most of the mononuclear TRACPase-positive cells had features similar to preosteoclasts. A mononuclear TRACPase-positive cell was a ruffled border and clear zone was reconstructed three-dimensionally by NIKON COSMOZONE 2SA. The reconstruction showed that this cell possessed a large clear zone and small ruffled border. Under the ruffled border, no lacuna was apparent; but there was disruption of the dentin surface. The results suggest that this cell was a mononuclear osteoclast and that it might have been in the process of making a new lacuna. PMID- 1750381 TI - Morphological and histochemical comparison of the cells elicited by ectopic bone implants and tibial osteoclasts. AB - Pellets of mineralized and demineralized bone and a composite mixture of mineralized and demineralized, devitalized bone particles were implanted subcutaneously on the dorsal body wall of young adult rats. Two weeks post implantation, the pellets were removed and processed for histochemical and morphological analyses. Rat proximal tibia was also processed for evaluation. The levels of tartrate-resistant acid phosphatase (TRAP) activity in the multinucleated giant cells (MNGCs) from each of the three implants and from osteoclasts were assessed using an image analyzer. The osteoclasts from the proximal tibia and the majority of MNGCs from the demineralized implants demonstrated high levels of TRAP activity. MNGCs from the mineralized implants showed either a low level or absence of TRAP activity. Most MNGCs from the composite implants exhibited a low level of TRAP activity; however, there was a population of cells that demonstrated a high level of reaction product, similar to that seen in the tibia and demineralized implant. Morphologically, osteoclasts from the proximal tibia and from the osteogenic demineralized implant exhibited ruffled borders. A small population of MNGCs from the composite implant also revealed osteoclastic features. In summary, MNGCs from the mineralized implant did not exhibit a level of TRAP reaction product or morphology similar to osteoclasts, while the majority of cells from the demineralized implant and a subpopulation of the MNGCs elicited by the composite implant did demonstrate TRAP expression and morphology similar to osteoclasts. The expression of osteoclastic characteristics in cells at an ectopic site may be dependent on accessory signals from the skeletal microenvironment; such signals appear to be absent from or incomplete in the mineralized implants but appear to be present when demineralized bone particles are implanted. PMID- 1750382 TI - Ultrastructure of palatal taste buds in the perihatching chick. AB - Palatal taste buds of perihatching chicks were examined by electron microscopy. Four intragemmal cell types were characterized. 1) Light: with voluminous, electron-lucent cytoplasm containing scattered free ribosomes, rough and smooth endoplasmic reticulum, plump mitochondria, sparse perinuclear filaments, occasional Golgi bodies, and numerous clear and dense-cored vesicles. Clear vesicles sometimes aggregate in a presynaptic-like configuration apposed to an axonal profile. These cells contained large, spherical, uniformly granular nuclei with one nucleolus. 2) Dark: with dense cytoplasm containing filamentous bundles surrounding the nucleus, occasional clear vesicles, centrioles, rough endoplasmic reticulum, and compact mitochrondria. The apical cytoplasm noticeably lacks dense secretory granules. Irregular to lobulated nuclei are densely granular, and contain scattered clumps of chromatin, adhering especially to the inner leaflet of the nuclear membrane, and at least one nucleolus. Cytoplasmic extensions of dark cells envelop other intragemmal cell types and nerve fibers. Light and dark cells project microvilli into the taste pore. 3) Intermediate: contain gradations of features of light and dark cells. 4) Basal: darker than the other intragemmal cell types and confined to the ventral bud region. Putative afferent synapses in relation to light cells, and axo-axonal contacts are described. While the appearance of axo-axonal contacts may be a transient developmental event, other bud features are consonant with observations in adult chickens and suggest that the peripheral gustatory apparatus is mature at hatching in this precocial avian species. PMID- 1750383 TI - Temporospatial study of the migration and distribution of cardiac neural crest in quail-chick chimeras. AB - It has been demonstrated that the septation of the outflow tract of the heart is formed by the cardiac neural crest. Ablation of this region of the neural crest prior to its migration from the neural fold results in anomalies of the outflow and inflow tracts of the heart and the aortic arch arteries. The objective of this study was to examine the migration and distribution of these neural crest cells from the pharyngeal arches into the outflow region of the heart during avian embryonic development. Chimeras were constructed in which each region of the premigratory cardiac neural crest from quail embryos was implanted into the corresponding area in chick embryos. The transplantations were done unilaterally on each side and bilaterally. The quail-chick chimeras were sacrificed between Hamburger-Hamilton stages 18 and 25, and the pharyngeal region and outflow tract were examined in serial paraffin sections to determine the distribution pattern of quail cells at each stage. The neural crest cells derived from the presumptive arch 3 and 4 regions of the neuraxis occupied mainly pharyngeal arches 3 and 4 respectively, although minor populations could be seen in pharyngeal arches 2 and 6. The neural crest cells migrating from the presumptive arch 6 region were seen mainly in pharyngeal arch 6, but they also populated pharyngeal arches 3 and 4. Clusters of quail neural crest cells were found in the distal outflow tract at stage 23. PMID- 1750384 TI - Pigment cell localizations in anuran ventral skin at climactic metamorphosis. AB - In anuran amphibians, the specific color pattern of the skin is expressed after metamorphosis, and its formation involves pigment cell migrations. Pigment cells are differently distributed in the tadpole, larval, and froglet skin. To learn more about their fate during metamorphic climax and in the young froglet, we focused our attention on the different localizations of larval melanophores and iridophores in the ventral skin of Rana esculenta before and during skin homing. Localizations of melanophores and iridophores can be elucidated at the developmental stages suggested by Taylor and Kollros (TK stages). At TK stage II (during early premetamorphosis), large melanophores beneath the larval skin are detected. At TK stage X, dispersed melanophores lie under bundles of muscular striated fibrils near the larval skin; they are also observed at the vascular level. At TK stage XVII (prometamorphosis), melanophores are extended on the inner side of the basement lamellar collagen. At the end of prometamorphosis, iridophores are located with melanophores in the separating space between attached basement collagen and derived basement collagen. At TK stage XX (earlier climax), melanophores and iridophores are detected inside the upper extremities of fractures opened in the derived basement collagen. At TK stage XXIV (later climax), both types of larval pigment cells are observed in the inner extremities of breaks derived from the fractures. During climax, these pigment cells occupy the well-formed breaks. At TK stage XXV in young froglet, the pigment cells remain alone in the breaks formed in the derived basement collagen. Briefly, breaks in the basement lamellar collagen are opened by invading cell processes of mesenchymal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750385 TI - Police brutality. The role of clinical forensic medicine. PMID- 1750386 TI - Unusual cases from Dubai, United Arab Emirates. AB - Dubai is one of the small countries of the United Arab Emirates located on the shores of the Persian Gulf in the Middle East. This report deals with two deaths: one an unusual method of suicide by hanging and the other, a death under investigation into whether it was accidental or suicidal. PMID- 1750387 TI - An analysis of the medicolegal autopsies performed in Adana, Turkey, in 1983 1988. AB - Data on 1,000 medicolegal autopsies have been compiled by the Morgue Department of the Adana branch of the Council of Forensic Medicine of Turkey, and have been reviewed to determine the local differences in causes of death, as well as age and sex distributions of decedents, in medicolegal deaths in this region. This is the first report on this subject in this region of Turkey. Unusual categories of death and incidences of death are also discussed. The results of this study show that the number of medicolegal autopsies and the rate of natural death in Adana are quite close to those of some other cities of Turkey and some foreign countries. Contrary findings are revealed in the frequencies of the causes of death. PMID- 1750388 TI - Medicoritual trephinations in modern Israel. AB - Two recent cases of ritual trephinations that were revealed during regular autopsies are described. The osteologic findings are discussed in relation to hospital craniotomy and ancient trephination, and the forensic practitioner is offered a set of criteria to differentiate properly between trephination and craniotomy. PMID- 1750389 TI - Human immunodeficiency virus infection in cases presenting to the Philadelphia Medical Examiner's Office. AB - Serum samples were available from 492 of 1,058 cadavers seen at the Philadelphia Medical Examiner's Office between August 4 and December 15, 1989. These sera were tested for the presence of antibodies to human immunodeficiency virus (HIV) by enzyme-linked immunosorbent assay (ELISA) and Western blot. The overall prevalence of HIV in the autopsy population was 2.24%. The following populations showed increased prevalence as compared to the total sampled population: blacks (3.60%, p less than 0.01), males (2.51%, n.s.), and homicide victims (3.74%, n.s.). Seroprevalence data from this study are compared with those from earlier studies of other related populations, with regard to overall prevalence and risk factor analysis. PMID- 1750390 TI - Gunshot residue, ten years later. AB - Gunshot residues may be central to a competent reconstruction of a shooting incident. When a young boy was shot in the neck by a playmate using a .22-caliber single-action revolver, permanent paralysis from mid-thorax downward ensued. Ten years later the victim sued the importer, the vendor, the German manufacturer, and the shooter's family. Investigative reports indicated "horseplay" and questionable emergency medical team care. Depositions were contradictory. The entry wound, removed at surgery, was fixed and processed for slides. The histopathologist referred to "black pigment granules" in the wound track. The 10 year-old slides and block were retrieved. The coverslip was removed from a representative slide that was examined under the scanning, x-ray dispersive microscope. The black granules contained amounts of lead, barium, and antimony far beyond any normal range. The firing range had to have been no greater than 6 12 in (15.24-30.48 cm). The case was promptly settled out of court. PMID- 1750391 TI - An unusual entrance wound associated with rimfire rifles. AB - In many cases of self-inflicted contact wounds of the head with rimfire rifles, we have noted that the entrance wound appears unusual: in 50% of cases studied, a pencil-like extension or zone of blackened and seared skin extends downward from the entrance. The most probable cause for the appearance of this wound is a momentary break in contact between the muzzle and skin as the victim reaches for the trigger with resultant escape of a jet of hot sooty gas. Whereas not unique for rimfire rifles, such a wound from a handgun is uncommon. PMID- 1750392 TI - Qualitative diatom analysis as a tool to diagnose drowning. AB - Since the 1950s, quantitative diatom analysis has been used successfully at the Department of Forensic Medicine at the University of Helsinki as a supportive method for diagnosing deaths by drowning. The reliability of the method was firmly established in 1986 by a study involving 107 probable cases of drowning. Since 1982, the quantitative analysis has been complemented with qualitative diatom analysis. This report presents potential applications of the latter method by describing its use in six cases of drowning. PMID- 1750393 TI - Death during immersion in water in childhood. AB - Drowning is a relatively common cause of accidental death in children. Autopsy records at the Adelaide Children's Hospital over a 27-year period from 1964 to 1990 were examined, and 58 cases were found where the cause of death was listed as drowning. In six cases, however, careful examination of the history and postmortem findings provided important additional information that suggested a more complex antemortem sequence of events. Specifically, four patients aged between 6 years, 10 months and 11 years were known to have had epilepsy. A further patient, an 8-year-old boy, died from a subarachnoid hemorrhage due to a bleeding cerebral arteriovenous malformation while swimming. The final patient, an 11-year-old boy who collapsed in a public swimming pool, was found at autopsy to have marked hypoplasia of the right coronary artery. In this series, six of 58 (10.3%) of the pediatric cases had additional underlying medical problems that could either have initiated the drowning episode or caused death due to alternate mechanisms. We present the clinicopathological findings in detail to demonstrate that a high index of suspicion must be maintained in all cases of pediatric drowning, not only for unnatural causes of death but also for additional natural disease processes that may have contributed significantly to the fatal episode. These findings may have particular relevance in jurisdictions where full postmortem examination is not always required by law. PMID- 1750394 TI - Diagnosis of electrical skin injuries. A review and a description of a case. AB - This paper presents a brief review of the results of research in the area of electrical skin injuries. It also includes a case report of a 5-year-old girl noted on her admission to the hospital to have injuries to the skin of her chest and left arm. Histological examinations demonstrated that the skin lesions were segmental and showed necrosis and inflammation. Deposits of calcium salts distinctly located to collagen fibers were observed below the regenerated epidermis at the periphery of two skin lesions of the chest wall, in the lower part of dermis at the periphery of a skin lesion of the left arm, and within connective tissue adjacent to elastic arteries and peripheral nerves from the thoracic cavity. The pattern of calcification localized to collagen fibers and situated both superficially and deeply in the skin in a zone of viable tissue close to necrotic tissue is characteristic of electrically induced lesions. Although there have been reports of deposition of calcium salts on collagen fibers after application of calcium salts in high concentration at the skin surface, the collagen calcification in the pattern observed in this patient is probably diagnostic of electrical injury. PMID- 1750395 TI - A 28-year (1963-90) study of homicide in Marion County, Oregon. AB - We describe 240 consecutive homicidal deaths that occurred in Marion County, Oregon, over a 28-year period (1963-90). An epidemiological assessment of the homicides yielded the following information: More than 91% of these deaths were primary homicides. In primary homicide, 63% of the victims and 88% of the offenders were male. In secondary homicide, 76% of the victims and all of the offenders were male. A high percentage of victims (83%) and offenders (84%) in primary homicide were Caucasian, as were 100% of victims and offenders in secondary homicide. About 12% of victims and 10% of offenders in primary homicide were Hispanic. Fifty-nine percent of primary homicides were intrasexual, as compared to 87% of secondary homicides. An intraracial pattern was found in 90% of primary homicides and in 100% of secondary homicides. The most frequent means of death in both primary and secondary homicides were firearms, physical beating, and stabbing. Strangers committed 80% of secondary homicides. This was in marked contrast to the victim-offender relationship found in primary homicides, where strangers were responsible for approximately 16% of the total, acquaintances for approximately 36%, and family members for approximately 48%. The overall clearance rate (i.e., the identification and charging of a suspect for the death) was 88%. PMID- 1750396 TI - Effect of carcass size on rate of decomposition and arthropod succession patterns. AB - Decomposition studies were conducted using two carcasses of domestic pigs, Sus scrofa L., 8.4 kg and 15.1 kg in weight, to determine the effects of carcass size on the rate of decomposition, composition of the arthropod fauna, and succession patterns. A total of 46 arthropod taxa were recovered during this study. No size related differences were observed between carcasses with respect to composition of the arthropod fauna or patterns of succession. A greater number of arthropods were observed attracted to the 15.1-kg carcass, and the rate of decomposition observed was more rapid for the 15.1-kg carcass than for the 8.4-kg carcass. Internal temperatures of the 8.4-kg carcass were more directly related to external ambient temperatures during the fresh and bloated stages of decomposition. During the decay stage, both carcasses generated internal temperatures significantly above ambient temperatures. Following this stage, internal temperatures fell to approximate ambient temperatures during the postdecay and remains stages. PMID- 1750397 TI - Cyanide ingestion. Case studies of four suicides. AB - Deliberate ingestion of cyanides is relatively rare, as reflected in the Registrar General's figures. There are no pathognomonic specific autopsy findings and even the distinctive smell may be missed by some individuals. We present four cases of cyanide ingestion, one of which appears to be the first reported case of magnesium cyanide poisoning in humans. The problems involved in investigating deaths from cyanide ingestion are discussed. PMID- 1750398 TI - The unusual accidental death of a pregnant woman by sexual foreplay. AB - This is the case of a young pregnant black woman who died during foreplay when her male partner with his hands accidentally forced air from her vaginal cavity into her uterine cavity, causing air embolization in the veins on the surface of her heart and her brain. Her premature infant was removed by cesarean section by emergency-room personnel after she died. The infant survived for 12 days before being declared brain dead. PMID- 1750399 TI - Demonstration of a fatal hemolytic transfusion reaction using immunoperoxidase techniques. AB - An immunoperoxidase technique coupled with monoclonal antibodies to the ABO blood group antigens was used to document a fatal ABO hemolytic transfusion reaction in a medical examiner's case. A case report with explanation of the technique is presented. PMID- 1750400 TI - The man in the scarlet cloak. The mysterious death of Peter Anthony Motteux. AB - Peter Anthony Motteux (1663-1718), a Huguenot refugee in London, established a literary reputation by completing Sir Thomas Urquhart's translation of Rabelais' Gargantua and Pantagruel, then Cervantes' Don Quixote. He later became an import export merchant. On his 55th birthday he donned his scarlet cloak and went out on the town. He picked up a prostitute and after some dalliance returned to her bordello. Shortly thereafter he was found dead, although the evidence is that he was in good health when he arrived. Literary evidence is that he died from assisted erotic asphyxia, a variant of autoerotic asphyxia, cf. the case of Frantisek Koczwara (Am J Forensic Med Pathol 5:145-149, 1984.) PMID- 1750401 TI - A simple dictation device. AB - A simple device for autopsy and scene dictation uses a small cassette recorder with a built-in microphone attached to a remote push-button switch worn on the belt or waistband. The recorder is carried in a shirt or scrub suit pocket and is functional under a protective apron or gown. The components, construction, advantages, and disadvantages of the device are presented. PMID- 1750402 TI - Sudden death of an elderly man with multiple malignant neoplasms. AB - With the lengthening of the human life span, cancer has become an increasingly important medical problem for the aged. It is not uncommon to find multiple primary neoplasms in elderly individuals. We recently investigated the death of an elderly man who had died suddenly and had three incidental malignant neoplasms, including a pleural mesothelioma, first diagnosed at autopsy. The importance of performing a complete medicolegal autopsy for epidemiological and statistical purposes is emphasized. PMID- 1750403 TI - Medicolegal problems in the health care field. PMID- 1750405 TI - Peer review for medical examiners. PMID- 1750404 TI - Nail gun suicides. PMID- 1750406 TI - Religious objections to autopsy. PMID- 1750407 TI - Rhabdomyolysis and heroin abuse. PMID- 1750408 TI - Proceedings of a symposium. Consensus Development Conference on Osteoporosis. October 19-20, 1990, Copenhagen, Denmark. PMID- 1750409 TI - Estrogens, bone mass, and osteoporotic fracture. PMID- 1750410 TI - Evaluating the benefits and risks of postmenopausal hormone therapy. AB - The evidence that estrogen protects against coronary heart disease is biologically plausible, consistent, and strong. These benefits have not been established by a randomized trial, however, so that the degree of protection against heart disease might have been overestimated because estrogen users tend to be healthier than nonusers. A randomized trial to determine whether estrogen alone or in combination with progestin protects against coronary heart disease should be given a high priority. Progestins generally attenuate the effects of estrogen on the concentrations of HDLC. It is not known whether this effect also limits the beneficial effects of estrogen on the risk of coronary heart disease. Recent studies suggest that estrogen may protect against coronary heart disease in other ways besides favorably altering serum concentrations of lipoproteins and that progestins might not have adverse effects on the risk of heart disease. Currently, theoretical concerns that progestins might be harmful seem outweighed by the evidence that they protect against endometrial cancer in women who have a uterus. For these women, some may find the side effects of progestins to be so bothersome that they prefer to take estrogen alone. This approach is reasonable so long as the patient has periodic endometrial biopsies for early detection of pre-malignant or malignant endometrial changes. Women without a uterus should take estrogen alone. Women who take long-term estrogen therapy appear to have about a 30% greater chance of developing breast cancer. On the other hand, breast cancer that develops while taking estrogen therapy might have a slightly better prognosis. Quantitative comparisons of fatal conditions suggest that the benefits of long-term therapy outweigh the risks. But these comparisons assume that all causes of deaths are equally important and do not adequately take account of other psychologic and physical effects of hormone therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750411 TI - Effect of calcitonin on bone mass and fracture rates. PMID- 1750412 TI - Theoretical overview: bone development, peak bone mass, bone loss, and fracture risk. PMID- 1750413 TI - Effect of calcium on skeletal development, bone loss, and risk of fractures. AB - In assessing the role of calcium, it must be stressed that calcium is not the cause of bone health but simply a necessary condition for it. It is mechanical usage that is of primary importance for bone. In just the same way iron is essential for hemoglobin synthesis and protein is essential for muscle mass, but neither is sufficient by itself. What, then, ought we to expect from a high calcium intake? Can we prevent estrogen-withdrawal bone loss? No. Calcium is not a substitute for estrogen, anymore than it is a substitute for exercise. Will calcium slow the remodeling loss that occurs with aging? Yes, to some extent; as calcium slows remodeling, it will inevitably slow remodeling-related loss. But most importantly, a high calcium intake will prevent calcium-deficiency bone loss. The only question, therefore, is the extent to which calcium deficiency loss may contribute significantly to bone fragility in various populations. The bone loss and fracture data reviewed briefly here indicate that an important portion of the osteoporotic fracture burden is calcium-related. What that portion is will be a function of the fraction of the population with inadequate intakes in any given country. Better than half of all adult American women have calcium intakes less than 500 mg/day, whereas only a small fraction of Dutch or Danish women, for example, would be under that level. Hence, a population-wide program to increase calcium intake in the United States would be likely to yield a greater benefit than in either the Netherlands or Denmark. That does not mean, of course, that there could not be substantial benefit to individuals with low intakes in all countries. Calcium intakes of greater than or equal to 1,500 mg are both safe and natural. While not all bone loss and low trauma fractures are due to low calcium intake, some almost certainly are. Adaptation to low intakes does occur, but it is seldom sufficient to compensate for the low intake. We cannot easily distinguish those who need more calcium from those who need less, and for that reason it makes good sense to ensure an adequate calcium intake for the entire adult population. What should that intake be? During adolescence, 1,500 mg will come close to ensuring the achievement of genetically programmed levels of peak bone mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750414 TI - The restoration of skeletal mass: a theoretic overview. PMID- 1750415 TI - Treatment of osteoporosis with sodium fluoride or parathyroid hormone. PMID- 1750416 TI - Use of bisphosphonates in the prevention of bone loss and fractures. PMID- 1750417 TI - Risk prediction in osteoporosis: a theoretic overview. PMID- 1750418 TI - Measurement of bone mineral density: current status. PMID- 1750419 TI - Exercise and its interaction with genetic influences in the determination of bone mineral density. PMID- 1750420 TI - Bone mass measurements in diagnosis and assessment of therapy. PMID- 1750421 TI - Biochemical markers of bone turnover: methodology and clinical use in osteoporosis. PMID- 1750422 TI - Biochemical markers of bone turnover in diagnosis and assessment of therapy. PMID- 1750423 TI - Helicobacter pylori and the etiology of duodenal ulcer: necessary but not sufficient. PMID- 1750424 TI - Is Helicobacter pylori a cause of duodenal ulcer? A methodologic critique of current evidence. AB - INTRODUCTION: Helicobacter pylori (HP) in the gastric antrum has been strongly associated with both duodenal ulcer (DU) and chronic active gastritis (CAG). The relationship between HP and DU has been interpreted as causal by many observers. An alternate hypothesis is that HP coincidently colonizes CAG, which is independently associated with DU by some yet-unknown mechanism. PURPOSE: To assess the extent to which a causal relationship between HP and DU has been demonstrated, we performed a methodologic critique of published clinical studies. We carried out a literature search to identify clinical studies that included at least 25 subjects. Of the eight studies we identified, six used a cross-sectional design and two used a prospective cohort design. We applied methodologic criteria to assess causation: strength of association, biologic gradient, temporality, and experiment. METHODS: A strong association between HP and DU was demonstrated in all eight studies. Biologic gradient and temporality were not assessed in any study. In the two experimental studies of therapy, loss of antral HP was associated with a decreased rate of DU relapse; however, we did not interpret this as sufficient to support causality because the effect may have been due to a direct mucosal action rather than eradication of HP. CONCLUSION: We conclude that published evidence does not establish HP as a cause of DU. One approach to address causality would be an observational cohort study of ulcer relapse to assess the temporal relationships between HP, CAG, and DU. PMID- 1750425 TI - The baseline electrocardiogram. PMID- 1750426 TI - Resting electrocardiograms as baseline tests: impact on the management of elderly patients. AB - PURPOSE: We evaluated management decisions of house staff in a university hospital emergency department (ED) to determine the impact of baseline electrocardiogram (ECG) results on the care of elderly patients. SUBJECTS AND METHODS: The study employed a prospective before-after research design. The subjects included internal medicine house staff assigned to the ED and the 47 elderly patients treated by them during 58 ED visits. The measures of impact on patient care included how often and in what ways comparison of baseline and ED ECG results changed the house staff's diagnostic impressions and treatment plans. To determine changes, we asked house staff to indicate their impressions and management plans before and after comparing baseline and ED ECG results. In addition, a panel of faculty members used a modification of the nominal group process to determine treatment changes and to estimate benefit to patients from the changes. RESULTS: House staff indicated that baseline ECG results led them to change diagnostic impressions during 13 (22%) and treatment plans during eight (14%) of the 58 visits. Six of the patients benefited from the treatment changes. The faculty judges indicated that baseline ECG findings would have altered their diagnostic impressions in eight (14%) and treatment decisions in three (5%) of the 58 cases, one of which would have benefited from the change. All patients for whom there were changes of impression or plan had prior histories of cardiovascular disease. CONCLUSION: We conclude that baseline ECGs provide ED house staff with diagnostic information that often leads to changes in management of elderly patients with prior histories of cardiovascular disease. Future studies should evaluate the efficacy of baseline ECGs in patients without such histories. PMID- 1750427 TI - Improving influenza vaccination rates for high-risk inpatients. AB - PURPOSE: In 1987, the Minneapolis Veterans Affairs Medical Center implemented an ongoing, multifaceted influenza vaccination program that targeted all high-risk outpatients followed at the medical center. While the program achieved and sustained vaccination rates of 60% or more for high-risk outpatients, vaccination rates for high-risk inpatients continued to be 25% or less. Beginning with the 1989-1990 immunization season, the "flu shot" program was extended to include all high-risk inpatients. Both the outpatient and inpatient components of the Minneapolis Flu Shot Program emphasized administrative and organizational elements. The program's goal was to achieve vaccination rates of at least 60% for both high-risk outpatients and inpatients. This study assesses the effectiveness of the inpatient program among elderly patients hospitalized on the medical service during the immunization season. PATIENTS AND METHODS: To estimate patient risk characteristics and vaccination rates, 50% of elderly patients who were discharged from the medical service during the immunization season were surveyed using a validated postcard questionnaire. Their responses were compared with the responses of elderly patients to the annual outpatient survey conducted to assess the "flu shot" program. RESULTS: Overall, 78.6% of elderly respondents discharged from the medical service during the immunization season were vaccinated. Vaccination rates within various high-risk subgroups all exceeded 70%. None of these vaccination rates for inpatient groups differed significantly from the rates for corresponding outpatients. CONCLUSION: An outpatient "flu shot" program that emphasizes administrative and organizational elements can be successfully expanded to high-risk inpatients. The vaccination rates attained with such a program may not only achieve but exceed the national health objective for influenza vaccination. PMID- 1750428 TI - Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent. AB - PURPOSE: Essential hypertension is, in some patients, complicated by impairment of insulin-mediated glucose disposal and hyperinsulinemia. Whether this metabolic disturbance is a consequence of the hypertensive process or whether it may precede, and thus possibly promote, the development of hypertension has been unknown. SUBJECTS AND METHODS: Searching for hereditary or familial defects in hypertension-prone humans, we prospectively investigated insulin sensitivity, plasma insulin and glucose, and serum lipoproteins in normotensive offspring of essential hypertensive as compared with age- and body habitus-matched offspring of normotensive families. RESULTS: Compared with 78 control subjects, 70 offspring of essential hypertensive parents had similar age (mean +/- SEM: 24 +/- 1 versus 24 +/- 1 years, respectively) and body mass index (22.3 +/- 0.2 versus 22.4 +/- 0.2 kg/m2), a blood pressure of 127/77 +/- 1/1 versus 123/76 +/- 1/1 mm Hg (p less than 0.05 for systolic), and significantly elevated (p less than 0.01 to 0.001) fasting plasma insulin levels (9.9 +/- 0.3 versus 8.6 +/- 0.3 microU/mL), serum total triglycerides (1.03 +/- 0.06 versus 0.83 +/- 0.03 mmol/L), total cholesterol (4.37 +/- 0.08 versus 3.93 +/- 0.07 mmol/L), low density lipoprotein cholesterol (2.45 +/- 0.08 versus 2.14 +/- 0.07 mmol/L), and total/high-density lipoprotein cholesterol ratio (4.3 +/- 0.1 versus 3.7 +/- 0.1). Insulin sensitivity was lower (9.4 +/- 0.7 versus 13.2 +/- 1.1 x 10(-4) x minute-1/microU/mL, p less than 0.001), while post-glucose-load plasma insulin levels were higher (p less than 0.05) in the 41 offspring of essential hypertensive parents than in the 38 offspring of normotensive parents so investigated. CONCLUSION: These findings demonstrate that young normotensive humans in apparently excellent health but with one essential hypertensive parent tend to have an impairment of insulin-mediated glucose disposal, hyperinsulinemia, and dyslipidemia. It follows that a familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism that can be detected before or at least at a very early stage of the development of high blood pressure as judged by resting blood pressure measurements. PMID- 1750430 TI - Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease. AB - PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease. PMID- 1750429 TI - The hypocholesterolemic effect of an antacid containing aluminum hydroxide. AB - STUDY OBJECTIVE: To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. DESIGN: A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. SETTING: Family practice clinics of two rural communities (kibbutzim) in Israel. PATIENTS: Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. INTERVENTION: After 2 months of dietary modification (low fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. MEASUREMENTS AND MAIN RESULTS: Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. CONCLUSIONS: An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients. PMID- 1750431 TI - Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis. AB - PURPOSE: Systemic mast cell disease (SMCD) follows an indolent course in most patients, but a significant number of patients die of neoplastic hematologic disorders. Reviews of the literature and retrospective studies in a single institution have defined features that may be associated with a poor prognosis, but prospective studies have been lacking. Therefore, we prospectively analyzed the relationship between clinical, laboratory, and hematopathologic findings and clinical outcome in a series of 46 patients with mast cell disease. This analysis was employed to both define clinically useful prognostic variables and describe the histologic evolution of bone marrow mast cell infiltration and its relationship to hematologic neoplasia. PATIENTS AND METHODS: Forty-six adult patients were referred to the National Institutes of Health (NIH) with clinical and/or pathologic evidence of mast cell proliferation. All patients had bone marrow examinations, and 10 patients underwent serial bone marrow biopsies. The diagnosis of SMCD required pathologic documentation of bone marrow mast cell infiltrates. The patients were followed for up to 13 years at the NIH (up to 30 years after the initial pathologic diagnosis of mast cell disease). Statistical analysis defined the correlation between variables and the presence of diagnostic bone marrow lesions. The Kaplan-Meier method was used to construct survival curves, and the effects of various variables on the survival time were examined. RESULTS: Thirty-two of 46 patients (74%) had a bone marrow biopsy diagnostic for SMCD. The remaining 14 patients were considered to have cutaneous mast cell disease (CMCD). Univariate analysis showed that hepatosplenomegaly, alkaline phosphatase level, absolute lymphocyte count, and age at onset of symptoms were positively correlated with SMCD, whereas hemoglobin level was negatively associated with diagnostic bone marrow lesions. With multivariate analysis, only hemoglobin and absolute lymphocyte count remained as significant independent predictors of bone marrow findings. No CMCD patient died or had significant clinical deterioration in the 1- to 30-year period of follow-up (median = 8.5 years), whereas 10 of 32 SMCD patients (31%) died from 1 to 22 years after diagnosis (median = 2.5 years) (p less than 0.0001). Univariate analysis revealed the following variables as significantly increasing the risk of death in patients with SMCD: later onset of symptoms, absence of cutaneous mastocytosis, thrombocytopenia, elevated lactate dehydrogenase (LDH) level, anemia, bone marrow hypercellularity, qualitative peripheral blood smear abnormalities, elevated alkaline phosphatase level, and hepatosplenomegaly. Multivariate analysis showed that only the age at onset of symptoms and LDH levels were significant independent predictors of survival. Eight of the 10 SMCD patients who died had myeloproliferative or myelodysplastic syndromes or acute nonlymphocytic leukemia. CONCLUSION: Our prospective study has defined a number of important variables in patients with clinical evidence of mast cell proliferation that can predict both the presence of SMCD and the likelihood of fatal disease. Since recent evidence suggests that mast cells derive from a bone marrow hematopoietic progenitor, SMCD may represent a myeloproliferative condition with the propensity to evolve into a neoplastic granulocytic disorder in a significant minority of patients. PMID- 1750432 TI - Frequent occurrence of asplenism and cholelithiasis in patients with autoimmune polyglandular disease type I. AB - PURPOSE: This study assesses the occurrence of asplenism and gallstones in patients with autoimmune polyglandular disease type I (APG I). PATIENTS AND METHODS: Nine patients with APG I (ages 14 to 48) were studied at the National Institutes of Health. Each patient received endocrine testing, a careful examination of his or her peripheral blood smear, lymphocyte immunophenotyping, a liver-spleen scan, and either an upper abdominal ultrasound or a computer assisted tomogram to evaluate the spleen and gallbladder. RESULTS: We documented asplenism in four patients and cholelithiasis in four patients, with two patients having both conditions. The patients with asplenism had Howell-Jolly bodies on peripheral blood smears, lack of splenic uptake by liver-spleen scan, and absent spleens by abdominal computed tomographic scan or ultrasound evaluation. The clinical presentation of the patients with cholelithiasis ranged from acute symptoms requiring surgery to asymptomatic gallstones. Lymphocyte immunophenotyping did not reveal consistent changes in either B- or T-cell subpopulations in the patients studied. CONCLUSION: Asplenism and gallstones occur frequently in patients with APG I. In addition to careful examination of the peripheral blood smear for Howell-Jolly bodies to screen for asplenism, we recommend an abdominal ultrasound to detect asplenism and/or gallstones in all patients with APG I. Appropriate immunizations and antibiotic coverage may be helpful in those patients with absent spleens. PMID- 1750433 TI - Familial occurrence of hypersensitivity to phenytoin. AB - PURPOSE: Therapy with anticonvulsants such as phenytoin, phenobarbital, and carbamazepine can be complicated by severe hypersensitivity reactions. Previous work has suggested that the predisposition to such reactions is based on an inherited abnormality in the detoxification of reactive metabolites of the drugs. However, there are no reports of familial occurrence of the reactions in the literature. In the current study, we examined a family in which three siblings developed hypersensitivity reactions to phenytoin, confirming the inheritance of a predisposition to the reactions. Detoxification of reactive metabolites of the anticonvulsants was studied in cells from the patients and their siblings. PATIENTS AND METHODS: Three siblings from a family of 12 siblings developed hypersensitivity reactions to phenytoin characterized by fever, rash, lymphadenopathy, and anicteric hepatitis. All recovered completely after discontinuation of treatment. One sibling tolerated phenobarbital without toxic sequelae. Peripheral blood mononuclear cells from the three patients and five additional siblings who had never taken anticonvulsants were exposed to oxidative metabolites of phenytoin, phenobarbital, and carbamazepine generated by a hepatic microsomal drug-metabolizing system in vitro. The toxicity of metabolites in the cells from the siblings was compared with that in cells from control subjects. RESULTS: Cells from each of the patients who had experienced a hypersensitivity reaction exhibited increased toxicity from metabolites of phenytoin and carbamazepine, while the cellular response to metabolites of phenobarbital was within normal limits. Cells from four of the other siblings showed an abnormal response to phenytoin metabolites, while cells from the final sibling detoxified phenytoin metabolites normally. CONCLUSION: Our observations on the patients confirm the inherited nature of phenytoin hypersensitivity reactions in vivo. In vitro studies demonstrated abnormal metabolite detoxification in the patients and several of their siblings. The detoxification defect included metabolites of phenytoin and carbamazepine but not of phenobarbital. A family history of a drug hypersensitivity reaction should alert physicians to the probability of a markedly increased risk of an adverse reaction in family members. In vitro assays to confirm adverse reaction risks may ultimately be able to provide individualized risk assessment for patients who must take anticonvulsants. PMID- 1750434 TI - National High Blood Pressure Education Program (NHBPEP) review paper on complications of shock wave lithotripsy for urinary calculi. AB - This decade has witnessed dramatic advances in the surgical management of urinary calculi. Today, most stones can be removed by minimally invasive means. In fact, the treatment of choice in 60% to 90% of patients with renal and ureteral calculi that need to be surgically removed is extracorporeal shock wave lithotripsy (ESWL). This article reviews indications for ESWL and discusses deleterious effects of ESWL. PMID- 1750435 TI - Psychologic effects of the diagnosis and treatment of hypercholesterolemia: lessons from case studies. AB - Some patients exhibit adverse psychologic responses to the diagnosis and treatment of hypercholesterolemia. These responses are, in part, a function of the patient's perception of the distinction between disease and illness and the patient's understanding of the probabilistic relationship between risk factors and associated diseases. Moreover, failure to acknowledge some of the specific complexities of hypercholesterolemia (e.g., natural fluctuations in serum cholesterol levels, variability of response to diet, etc.) may result in considerable anxiety. Clinicians should recognize and address these potential sources of dysfunctional psychologic reactions when they counsel hypercholesterolemic patients. PMID- 1750436 TI - Refractory hypoxemia in right ventricular infarction from right-to-left shunting via a patent foramen ovale: efficacy of contrast transesophageal echocardiography. PMID- 1750437 TI - Cocaine-associated thrombocytopenia. AB - In this retrospective report, four male intravenous cocaine users are described with thrombocytopenia temporally related to the use of the drug. Mucosal bleeding and megakaryocytic hyperplasia occurred in all patients. The cocaine thrombocytopenia relationship was especially apparent in one individual who developed thrombocytopenia on two separate occasions after intravenous cocaine use. Three patients were treated successfully with high doses of intravenous gamma globulin and steroids, while one patient required splenectomy. Along with the widespread use of cocaine in our society has come the recognition of a number of adverse effects of the drug. Thrombocytopenia may be added to a list that includes myocardial infarction and central nervous system complications. PMID- 1750438 TI - The rashes of dermatomyositis in a black patient. PMID- 1750439 TI - Pericarditis: an unusual manifestation of giant cell arteritis. PMID- 1750440 TI - Interleukin-4 levels in the eosinophilia-myalgia syndrome. PMID- 1750441 TI - Academic medicine: no longer an individual sport. PMID- 1750442 TI - "Transfer" and "turning" fractures in nursing home patients. PMID- 1750443 TI - Upright tilt-table testing in patients with syncope. PMID- 1750444 TI - RNA-directed molecular hybridization screening: evidence for inapparent chlamydial infection. AB - Both clinical and epidemiological data suggest that inapparent infection by Chlamydia trachomatis occurs in humans. To confirm and study such infections, we developed a hybridization screening system directed toward chlamydial ribosomal RNA (rRNA). Six restriction endonuclease fragments derived from the cloned rrnA operon of chlamydial serovar L2(434) were tested as hybridization screening probes, but only one fragment encoding the 5' portion of the 16s rRNA gene plus some upstream flanking sequence was both sensitive and highly specific in such experiments. In Northern slot blot assays, hybridization analyses with this fragment as probe routinely detected one picogram or less of chlamydial RNA when that RNA was bound to membranes alone or as part of a mixture with a vast excess of mammalian RNA. The probe did not hybridize to RNA from mammalian and relevant bacterial sources but did hybridize to rRNA from B (ocular) and E (genital) serovars of C. trachomatis. Experiments using RNA from conjunctival biopsies and standard conjunctival swab samples from cynomolgus monkeys showed that the probe reliably distinguishes between known chlamydia-infected and uninfected samples. This suggests that it may be useful for clinical screening. Characterization assays for the RNA-directed probe screening system in this monkey model of trachoma provide initial molecular evidence that ocular chlamydial infection may persist longer than previously thought, based solely on direct fluorescence antibody assay (DFA) and culture analyses. PMID- 1750445 TI - Evaluation and management of patients with chronic fatigue. AB - Chronic fatigue is a common and disabling problem in primary care practice. The differential diagnosis of chronic fatigue is extensive and includes medical disorders, altered physiologic states (eg, pregnancy, exertion), psychiatric disorders, lifestyle derangements, drugs, and controversial entities (eg, chronic candidiasis, food allergies, environmental illness, and chronic fatigue syndrome). The most common diagnoses are psychiatric disorders, including mood, anxiety, and somatoform disorders. A comprehensive approach to diagnosis and management is necessary, including structured psychiatric interviewing, functional assessment, and elicitation of the patient's diagnostic beliefs. Patients often believe they are suffering from an organic medical disorder (eg, viral or immunologic) and resist psychiatric labelling of their symptoms and referral to mental health practitioners. Establishing and maintaining rapport, having a flexible approach, and demonstrating a personal concern for the patient is essential. Drug therapy for specific psychiatric and medical illnesses and cognitive-behavioral approaches for enhancing coping mechanisms are effective. PMID- 1750446 TI - Computer imaging analysis of the correlation between intensities of glomerular immune-deposits and histopathology in patients with IgA nephropathy. AB - The relationship between the intensities of IgA, C3c, and C9 deposition in renal glomeruli and the severity of histopathologic injuries in patients with IgA nephropathy was examined using Microscope-Photometer 01K and a computer. Percentages of glomerular adhesion to Bowman's capsules, crescent formation, and glomerular sclerosis were calculated in the renal specimens. There was a significant correlation between the intensity of each C3c and C9 deposition in glomeruli and the degree of glomerular adhesion to Bowman's capsules and crescent formation in patients with IgA nephropathy. There was no significant correlation between the intensity of C3c or C9 deposition in glomeruli and the degree of glomerular sclerosis. No relationship was found between the intensity of IgA deposition in glomeruli and the degree of histopathologic injuries. The patients with negative or trace amounts of glomerular C3c deposits showed less severe glomerular injuries. Thus, the intensity of C3c and C9 deposition in glomeruli appears to be one of the critical factors responsible for the active progression of glomerular inflammatory process in patients with IgA nephropathy. PMID- 1750447 TI - Gastric mucosal cytoprotection in the rat by scavenging oxygen-derived free radicals. AB - Oxygen-derived free radicals are cytotoxic and promote tissue damage. Dimethyl sulfoxide (DMSO) and allopurinol scavenge hydroxyl radicals, and the latter agent also inhibits the enzyme xanthine oxidase, which is responsible for the formation of superoxide anions. These agents were given daily by gavage (1 ml/d). After 2 days of administration as 1, 2, or 5% solutions, the H+ output of the rat with or without pyloric ligation was not significantly affected. After six hours reserpine (5 mg/kg i.p.) or serotonin (50 mg/kg i.p.) produced ischemic mucosal injury in all stomachs (39 +/- 5.2 mm2 and 25.9 +/- 2.8 mm2, mean +/- standard error of the mean [SEM], n = 10). Pretreatment for 2 days with 1 ml/d of 1% allopurinol or DMSO significantly (p less than 0.001) protected the rat against the reserpine (23 +/- 2.1 mm2 and 24 +/- 1.9 mm2, respectively, vs 39 +/- 5.2 mm2, n = 10) and serotonin injury (10 +/- 1.5 mm2 and 11 +/- 1.8 mm2, respectively, vs 25.9 +/- 2.8 mm2, n = 10). However, 2 days pretreatment with 1 ml/d of 2% allopurinol or DMSO was more effective (p less than 0.001) in this respect, and injury only developed in 40% of the rats given reserpine (8 +/- 1.2 mm2 and 9 +/- 1.6 mm2) and in 20% of those given serotonin (2.4 +/- 0.4 mm2 and 1.9 +/- 0.5 mm2). Similar pretreatment with 5% solutions completely protected the rat stomach against the reserpine and serotonin injuries without significantly influencing the H+ output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750448 TI - Case report: extensive brain calcification in hypoparathyroidism. AB - It is well known that most patients with hypoparathyroidism have radiologically detectable basal ganglia calcification. Not as well known is that the brain calcinosis may be more extensive. We describe a 55-year-old woman with a 44-year history of symptomatic idiopathic hypoparathyroidism who has extensive calcification of her cerebrum and cerebellum as well as her basal ganglia, evident on computed tomography of the head. When first evaluated here 32 years ago, plain radiography of the skull demonstrated calcification of both caudate and lentiform nuclei (basal ganglia). Despite fair control of her serum calcium level, she has developed focal seizures, possibly related to the calcinosis of her brain. PMID- 1750449 TI - Case report: salmonellosis complicated by leukocytoclastic vasculitis. AB - We report the case of a healthy young Hispanic man with Salmonella typhimurium bacteremia and leukocytoclastic vasculitis. Leukocytoclastic vasculitis has not been previously reported as a complication of salmonella gastroenteritis and bacteremia. Salmonella gastroenteritis is rarely associated with bacteremia in healthy young adults. PMID- 1750450 TI - Prospects of gene therapy for hemoglobinopathies. AB - Gene therapy offers the promise of a definitive cure of the hemoglobinopathies and thalassemias. The background of gene therapy for these disorders is discussed along with the obstacles that must be overcome before this promise becomes reality. PMID- 1750451 TI - Community responsive medicine: defining an academic discipline. AB - Academic medicine is entering a period of introspection created by changing patterns of health and disease and changing patterns in reimbursement and health policy. To respond to existing health challenges, innovative strategies for health care delivery and education must be devised. The migration of medical education and health care delivery into centralized and frequently difficult-to access campuses is being reviewed by payors, policy analysts, and purchasers of care. One proposed solution to this problem responds to the identified shortcomings in medical education and some of the failures of our health care delivery system. Community Oriented Primary Care (COPC) and the related discipline of Community Responsive Medicine define health-oriented strategies that blend traditional primary care and public health. The classroom in Community Responsive Medicine is the community. The curriculum is defined by the elements and skills necessary to improve the health status of the target community. The model allows the student and resident to appreciate and experience the entire spectrum of health and disease and to understand the sequence of events that may lead to illness. Tertiary care is a critical curriculum component, but in Community Responsive Medicine the curriculum is balanced between the ambulatory and tertiary care settings. Community Responsive Medicine defines a role for new leadership that can create responsive educational and health care delivery systems accountable to the communities they serve. PMID- 1750452 TI - The endothelium--a key regulator of vascular tone. AB - Emerging evidence suggests the endothelium produces several substances capable of locally regulating organ blood flow. Vasoactive prostaglandins, endothelium derived relaxing factor, and endothelin are examples of these vasoactive substances. Abnormalities of endothelial function may contribute to the pathogenesis of disease in several circumstances, including hypertension, diabetes, and septicemia. Evidence for the endothelium as a regulator of regional perfusion and several of the endothelium-derived substances and their potential role in disease are reviewed. PMID- 1750453 TI - Elevated fetal plasma lactate produces polyhydramnios in the sheep. AB - In human fetuses with hemolytic diseases such as erythroblastosis fetalis, hydrops fetalis or polyhydramnios often develops. The mechanism(s) that produces these fluid imbalances is unknown, although lactate concentrations have been reported to be elevated in hydropic human fetuses with erythroblastosis. In this study we explored the role of lactate in producing fetal fluid imbalances. In seven near-term fetal sheep, we infused 5 mol/L sodium lactate at a rate of 10 mmol/hr for 3 days. Fetal plasma lactate rose by 6.0 +/- 1.0 (mean +/- SE) mmol/L above control. Fetal plasma osmolality and Na+ increased slightly, Cl- decreased, and bicarbonate rose in proportion to the Cl- decrease. Fetal renal lactate excretion was 1.1 +/- 0.3 mmol/hr while Na+ excretion was 10.6 +/- 1.9 mEq/hr. Fetal urine flow increased by 1.9 +/- 0.4 L/day and the urine remained hypotonic relative to fetal plasma throughout the infusion. Amniotic fluid lactate and Na+ rose during the infusion period and remained elevated during a 24-hour recovery period. Amniotic plus allantoic fluid volume at autopsy was 5.3 +/- 0.8 L compared with a normal of 0.5 to 1.0 L. There was little evidence of fetal edema. In summary, a moderate sustained elevation in fetal plasma lactate concentration appears to be a powerful osmotic agent for fetal accumulation of fluid from the maternal compartment over a period of days. This may be the primary mechanism whereby hydrops fetalis or polyhydramnios develops in severely anemic human fetuses. PMID- 1750454 TI - Oral-nasal membranes are not the major route for fetal absorption of amniotic fluid arginine vasopressin. AB - Intraamniotically injected substances such as arginine vasopressin and digoxin have been found to rapidly appear in the ovine fetal circulation, irrespective of whether the fetal esophagus has been ligated or occluded. To determine if the ovine fetal oral-nasal membrane plays a significant role in this fetal absorption of amniotic substances, we used two groups of chronically catheterized fetal sheep with a surgical glove sewed over the fetal head to prevent access of the head to amniotic fluid. In the first group 22.5 micrograms of arginine vasopressin was injected into the amniotic cavity; in the second group 22.5 micrograms was injected into the glove over the fetal head. We found that, after injection into the amniotic cavity, there were rapid and highly significant increases in amniotic fluid arginine vasopressin concentrations, from 6.1 +/- 1.3 to 51,249 +/- 18,182 pg/ml (mean +/- SE) (p less than 0.00001). Concurrently there was a rapid increase in fetal plasma arginine vasopressin concentrations from 4.5 +/- 1.3 to 93.8 +/- 18.9 pg/ml (p less than 0.00001). The increase was significant within 15 minutes and reached a maximum at 60 minutes after the injection. Fetal arterial pressure increased by 10 +/- 2 mm Hg, whereas heart rate decreased by 30 +/- 5 beats/min (p less than 0.00001). In contrast, after the injection into the glove covering the fetal head, there were no significant changes in any of the measured parameters. This suggests that the ovine fetal oral-nasal membrane is not a significant route of absorption of amniotic fluid arginine vasopressin and that the most likely route of absorption is the vascularized fetal surface of the placenta and vascularized fetal membranes, i.e., the intramembranous pathway. PMID- 1750455 TI - Amniotic fluid volume response to esophageal occlusion in fetal sheep. AB - Although ovine and human fetuses swallow considerable volumes of fluid, the impact of absence of fetal swallowing on amniotic fluid volume regulation is unclear. To study the role of fetal swallowing on urine production and amniotic fluid, seven ovine fetuses (126 +/- 1 days) were chronically prepared with fetal bladder and vascular catheters, an esophageal flow probe, an inflatable esophageal cuff, and amniotic fluid catheters. In the five fetuses that underwent esophageal ligation after the control period, fetal swallowing averaged 0.27 ml/min before occlusion. In response to esophageal occlusion, significant increases were noted in fetal plasma arginine vasopressin (6.9 +/- 2.6 to 16.6 +/ 4.4 pg/ml) and urine osmolality (159 +/- 1 to 324 +/- 30 mOsm/kg), whereas urine volume (0.25 ml/min) did not change. Amniotic fluid volume increased nearly threefold after 3 days of esophageal occlusion (582 +/- 180 to 1530 +/- 271 ml). Amniotic fluid volume remained normal (334 to 419 ml) in the one fetus in which the occluder did not inflate. In the one fetus in which the esophagus was occluded at surgery, amniotic fluid volume was increased after the surgical recovery period (1489 ml). These data indicate an important role of fetal swallowing in amniotic fluid homeostasis and the potential interaction of swallowing with fetal urine production. PMID- 1750456 TI - Angiotensin II vascular smooth-muscle receptors are not down-regulated in near term pregnant sheep. AB - Normal human and ovine pregnancies are associated with elevated plasma angiotensin II levels and refractoriness to the vasoconstrictor effects of infused angiotensin II, which is greater in the ovine uteroplacental vascular bed than in the systemic vasculature. It remains unclear whether this refractoriness reflects alterations in angiotensin II vascular smooth-muscle receptor density or affinity. We examined the angiotensin II vascular smooth-muscle receptor in nonpregnant (n = 12) and near-term pregnant (130 +/- 3 days [mean +/- SD], n = 10) sheep, comparing binding characteristics on plasma membranes prepared from the medial layer of aorta, mesenteric artery, and uterine artery. Plasma angiotensin II levels were increased threefold to fourfold (p less than 0.001) in pregnant ewes. A single class of high-affinity angiotensin II vascular smooth muscle receptor was identified in each type of artery. Receptor density was similar in nonpregnant and pregnant mesenteric artery (92 +/- 21 vs 103 +/- 40 fmol/mg protein, respectively), aorta (186 +/- 29 vs 220 +/- 46 fmol/mg protein), and uterine artery (59 +/- 20 vs 77 +/- 20 fmol/mg protein) tissue. Receptor affinity also was unchanged during pregnancy. Because changes in the density and affinity of the angiotensin II vascular smooth-muscle receptor were not observed in near-term pregnant ewes, the attenuated vasoconstrictor responses seen during pregnancy do not reflect receptor down-regulation or decreased affinity. PMID- 1750457 TI - Effects of hyperglycemia on mitochondrial morphology in the region of the anterior neuropore in the explanted rat embryo model: evidence for a modified Reid hypothesis as a mechanism for diabetic teratogenesis. AB - Congenital malformations are the leading cause of the increased perinatal mortality in the infants of insulin-dependent diabetic mothers. The mechanisms(s) of diabetic teratologic development has yet to be defined. Hyperglycemia is known to depress aerobic metabolism in many organisms and cell lines. Reid hypothesized that exposure to hyperglycemia could result in decreased mitochondrial biogenesis in embryonic cells. Should these cells suddenly be changed to an environment of lower glucose concentration, decreased energy capabilities would exist until sufficient numbers of mitochondria could be regenerated. Such cells may not be capable of meeting temporal-spatial requirements, thereby resulting in structural abnormalities. In our study the explanted rat embryo model demonstrated that in the head-fold region hyperglycemia produced morphologic alterations of mitochondria but no difference in the number of mitochondria per cell. Specifically, embryos cultured in euglycemia demonstrated orthodox mitochondrial configuration, whereas those cultured in hyperglycemia had mitochondria in a condensed configuration. These findings were reversible. A modification of Reid's original hypothesis may provide an explanation for the mechanism of diabetic teratologic development. PMID- 1750458 TI - Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. AB - To assess the longitudinal changes in insulin release and insulin sensitivity in nonobese normal women during gestation, six women were evaluated with oral glucose tolerance testing, body composition analysis, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp before conception, at 12 to 14 weeks, and at 34 to 36 weeks' gestation. There was a significant increase in the insulin/glucose ratio (p = 0.028) during the oral glucose tolerance test during gestation. There was also a significant 3.0- to 3.5-fold increase throughout gestation in first-phase (p = 0.001) and second-phase (p = 0.0001) insulin release during the intravenous glucose tolerance test. Peripheral insulin sensitivity was estimated as the glucose infusion rate (in milligrams per kilogram fat-free mass per minute) during the hyperinsulinemic-euglycemic clamp. There was a significant (p = 0.0003) 56% decrease in insulin sensitivity through 36 weeks' gestation. These results are the first to prospectively evaluate the longitudinal changes in maternal carbohydrate metabolism from the time before conception through late gestation with newer methods such as the hyperinsulinemic euglycemic clamp. PMID- 1750459 TI - The changing glycemic response to exercise during pregnancy. AB - This study was designed to test the hypothesis that pregnancy reverses the nonpregnant hyperglycemic response to sustained exercise. Serial data were obtained from 75 exercising women. Before pregnancy, exercise produced an intensity-dependent increase in blood glucose that averaged 1.5 mmol/L at high intensities. By the eighth week this response was blunted and blood glucose increased only when exercise intensity exceeded 80% of maximum. At 15 weeks this progressed and was not associated with a change in either the insulin or catecholamine response. By the twenty-third week exercise produced a decrease in blood glucose that was no longer related to exercise intensity. We conclude that the hypothesis is correct and speculate that the early change in the response is related to decreased hepatic glucose release coupled with increased glucose oxidation. In late pregnancy this is probably accentuated by fetoplacental demands. PMID- 1750460 TI - The changing thermal response to endurance exercise during pregnancy. AB - This study was designed to test the hypothesis that the thermal response to endurance exercise is altered by the thermal adaptations to pregnancy. Accordingly, rectal temperature was monitored in 18 recreational athletes before, during, and after 20 minutes of continuous exercise before conception and every 6 to 8 weeks during pregnancy. Mean exercise intensity was 64% of VO2 max before conception and did not change during pregnancy. However, the peak rectal temperature reached during exercise decreased by 0.3 degrees C at 8 weeks and then fell at a rate of 0.1 degrees C per lunar month through the thirty-seventh week. This appeared to be related to changes in resting temperature, thermal mass, sweating threshold, and venous capacitance that began early in pregnancy. These data suggest that the magnitude of any exercise-associated thermal stress for the embryo and fetus is markedly reduced by the maternal physiologic adaptations to pregnancy. PMID- 1750461 TI - Maternal levels of prostacyclin, thromboxane, vitamin E, and lipid peroxides throughout normal pregnancy. AB - In normal pregnancy the vasodilating actions of prostacyclin and the antioxidant activity of vitamin E are important for normal physiologic function. Thromboxane and lipid peroxides oppose these actions by promoting vasoconstriction and peroxidation reactions, respectively. An imbalance between thromboxane and prostacyclin and between lipid peroxides and antioxidant activity is implicated in pathologic states such as preeclampsia. We hypothesized that in normal pregnancy there would be a balance in the ratios of prostacyclin to thromboxane and of vitamin E to lipid peroxides that would favor prostacyclin and vitamin E. Blood samples were collected from normally pregnant women throughout gestation and analyzed for prostacyclin, thromboxane, vitamin E, and lipid peroxides. Serum levels of lipid peroxides remained relatively stable throughout gestation, but the levels of vitamin E progressively increased. Plasma levels of prostacyclin progressively increased with advancing gestation, whereas levels of thromboxane progressively decreased. Therefore the ratios of both prostacyclin/thromboxane, and vitamin E/lipid peroxides progressively increased during pregnancy. The increase in the ratios was highly correlated, r = 0.94. We conclude that the changes in the maternal concentrations of these compounds and the progressive increase in the ratios of prostacyclin/thromboxane and vitamin E/lipid peroxides suggest that the vasodilating actions of prostacyclin and the antioxidant activity of vitamin E are progressively favored with advancing gestation in normally pregnant women. PMID- 1750462 TI - The imbalance between thromboxane and prostacyclin in preeclampsia is associated with an imbalance between lipid peroxides and vitamin E in maternal blood. AB - Preeclampsia is associated with an imbalance between thromboxane and prostacyclin. The cause of the imbalance is unknown. Preeclampsia sera contain cytotoxic factors that can damage endothelial cells. Lipid peroxides can damage cell membranes, so elevated levels in the mother's blood could be related to endothelial cell injury and decreased prostacyclin in preeclampsia. This study determined maternal plasma levels of thromboxane and prostacyclin and serum levels of lipid peroxides and vitamin E in women with normal pregnancy (n = 12), mild preeclampsia (n = 16), and severe preeclampsia (n = 19) between 36 and 40 weeks' gestation. In normal pregnancy the ratio of thromboxane to prostacyclin (0.63) favored prostacyclin, and the ratio of lipid peroxides to vitamin E (0.43) favored vitamin E. Prostacyclin was significantly decreased in both mild and severe preeclampsia. Thromboxane was not increased in mild preeclampsia but was significantly increased in severe preeclampsia. The ratio of thromboxane to prostacyclin was increased in mild preeclampsia (0.77) and greatly increased in severe preeclampsia (1.94). Lipid peroxides were significantly increased in mild preeclampsia and increased further in severe preelcampsia. Vitamin E levels were unaltered in mild preeclampsia but significantly decreased in severe preeclampsia. The ratio of lipid peroxides to vitamin E was increased in mild (0.52) and greatly increased in severe (1.09) preeclampsia. We concluded the following: (1) Maternal plasma prostacyclin is decreased in both mild and severe preeclampsia, but thromboxane is increased only in severe cases. (2) Lipid peroxides are significantly increased in both mild and severe preeclampsia and vitamin E is significantly decreased in severe preeclampsia. We speculate that this imbalance could result in endothelial and platelet cell damage and in decreased prostacyclin and increased thromboxane synthesis. (3) Preeclampsia is associated with an imbalance not only between thromboxane and prostacyclin but also between lipid peroxides and vitamin E in maternal blood. The imbalances progressively favor thromboxane and lipid peroxides with the increasing severity of preeclampsia, which is consistent with the clinical symptoms of this disorder. PMID- 1750463 TI - Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension. AB - Increased free radical activity has been implicated in the pathogenesis of pregnancy-induced hypertension. This article investigates whether changes in antioxidant systems contribute to this condition. Two extracellular (plasma thiols and ceruloplasmin) and two intracellular (red blood cell lysate thiols and red blood cell superoxide dismutase) antioxidant markers were assayed in 25 nonpregnant women, 16 pregnant women with normal blood pressure, 19 women with pregnancy-induced hypertension, and 13 women with proteinuric pregnancy-induced hypertension. In the normotensive pregnant group (in comparison with the nonpregnant group) the plasma thiol level was reduced (p less than 0.001) and the ceruloplasmin level raised (p less than 0.005), suggesting increased free radical activity. The lysate thiol level increased (p less than 0.005), which may reflect a compensatory protective response. In the hypertensive pregnant groups the lysate thiol rise was not present. These red blood cells may be more prone to oxidative stress. Whether this situation is a cause or an effect of oxidative stress in pregnancy-induced hypertension has yet to be elucidated. PMID- 1750464 TI - Selective effects of preeclamptic sera on human endothelial cell procoagulant protein expression. AB - Current concepts of preeclampsia suggest that dysfunction of maternal vascular endothelium in vivo is a central pathogenetic feature of this syndrome. This hypothesis is suggested by the activation of the coagulation cascade associated with preeclampsia and evidence for a role of endothelium in maintaining thromboresistance. Previous in vitro studies with monolayers of human umbilical vein endothelial cells demonstrated direct cytotoxic effects of sera from preeclamptic parturients. In the current studies, we have examined the in vitro expression of three procoagulant protein activities regulated by endothelial cells: cellular fibronectin, an important mediator of platelet aggregation known to be elevated in preeclamptic women in vivo; tissue factor, the most potent endogenous procoagulant activity; and von Willebrand factor, a major component of coagulation factor VIII. Monolayer cultures of human umbilical vein endothelial cells were incubated with pregnancy sera for 24 hours before these proteins and activities were quantified. Exposure of identical endothelial cell cultures to predelivery preeclamptic sera caused significantly greater release of cellular fibronectin than postdelivery preeclamptic or predelivery or postdelivery normal pregnancy sera (p less than 0.05). However, neither tissue factor activity nor von Willebrand factor expression appeared to be increased preferentially by preeclamptic sera. The data indicate that sera from women with preeclampsia induce a selective, but not a generalized, activation of endothelial cell procoagulant protein production. PMID- 1750465 TI - Potential role of endothelin-1 in normal and hypertensive pregnancies. AB - Endothelins are the most potent naturally occurring vasoconstrictors yet discovered. Both normal and abnormal pregnancies are associated with significant changes in vascular smooth muscle; therefore the potential role of endothelin in pregnancy was investigated. Plasma immunoreactive endothelin-1 concentration was measured by radioimmunoassay in blood from women with normal pregnancy and preeclampsia and in cord blood from normal pregnancies. Endothelin-1 levels were elevated in pregnant women during labor when compared with levels in nonpregnant women and patients with normal pregnancies before labor. Preeclampsia in nonlaboring women before treatment was associated with higher endothelin values when compared with values in normal nonlaboring patients and women with preeclampsia after magnesium sulfate infusion. The umbilical venous concentration of endothelin was 10 times higher than normal pregnant levels and four times higher than levels in laboring patients. PMID- 1750466 TI - Endothelin-1-induced vasoconstriction is not mediated by thromboxane release and action in the human fetal-placental circulation. AB - The vasoconstrictor peptide endothelin-1 (8 x 10(-10) to 1 x 10(-8) mol/L) significantly increased fetal-placental perfusion pressure in vitro in a cumulative manner from 30 +/- 2 to 123 +/- 25 mm Hg (mean +/- SEM, n = 5, p less than 0.0005, analysis of variance). Accompanying this vasoconstriction was a corresponding reduction in fetal-placental perfusate flow rate. Measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in the fetal-placental perfusate revealed a significant reduction in their release (p less than 0.0096 and p less than 0.0004, analysis of variance, respectively) when corrected for flow rate. Neither the thromboxane synthesis inhibitor dazoxiben (10(-6) mol/L) nor the thromboxane receptor antagonist SQ29548 (10(-6) mol/L) was able to block the vasoconstrictor actions of endothelin-1. Therefore endothelin-1-induced vasoconstriction in the human fetal-placental circulation does not appear to be mediated by thromboxane release or action. The stimulus to eicosanoid release in the fetal-placental circulation may be hydrodynamic, i.e., flow or shear stress. PMID- 1750467 TI - An endothelial cell model for the investigation of the molecular regulation of fetal vascular tone. AB - Human umbilical vessels are not innervated, and hence regulation of tone in these vessels must come from locally derived vasoactive substances such as prostacyclin. To evaluate the regulation of prostacyclin production by human umbilical vein endothelial cells, we incubated confluent cultures of these cells with various concentrations of inflammatory mediators (endotoxin, interleukin-1 beta, and tumor necrosis factor), protein kinase C agonists (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate), and calcium ionophores (A-23187 and ionomycin). Human umbilical vein endothelial cells were prepared from term pregnancies, and confluent cultures were incubated with test substances for 16 hours. Prostacyclin was measured as its metabolite 6-keto-prostaglandin F1 alpha by radioimmunoassay. Concentration-related increases in 6-keto-prostaglandin F1 alpha production were observed in response to endotoxin, cytokines, phorbol esters, and calcium ionophores. We conclude that human umbilical vein endothelial cell prostacyclin production is influenced by several intracellular messengers and that human umbilical vein endothelial cells may provide a useful in vitro model for investigating the physiology and pathophysiology of umbilical vessel vascular tone. PMID- 1750468 TI - Prenatal diagnosis with fetal cells isolated from maternal blood by multiparameter flow cytometry. AB - A long-sought goal of medical genetics has been development of prenatal diagnostic procedures that do not endanger the conceptus. Reliable and universal screening for cytogenetic disorders would require analysis of fetal cells isolated from the maternal circulation. This would be applicable to all pregnant women, irrespective of their ages or histories. In the current study fetal nucleated erythrocytes were flow sorted on the basis of four parameters: cell size, cell granularity, transferrin receptor, and glycophorin-A cell surface molecule. By polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific deoxyribonucleic acid sequences, male fetuses were correctly identified among flow-sorted samples in 12 of 12 (100%) pregnancies; female fetuses were correctly identified in 5 of 6 (83%) pregnancies. We also achieved the prenatal diagnosis of fetal aneuploidies by use of flow-sorted nucleated fetal erythrocytes and in situ hybridization with chromosome-specific deoxyribonucleic acid probes: one case of trisomy 21 that was detected in maternal blood taken 1 week after chorionic villus sampling and one case of trisomy 18 that was detected in maternal blood taken immediately before chorionic villus sampling. Although our results are promising, additional data on the background sensitivity and specificity of in situ hybridization in flow-sorted fetal cells will be necessary to minimize subjective interpretation and permit clinical application. PMID- 1750469 TI - Absence of hyperinsulinemia in isoimmunized fetuses treated with intravascular transfusion. AB - We serially sampled blood from fetuses of five severely isoimmunized pregnancies at the time of each intrauterine intravascular transfusion and at birth. We were unable to demonstrate either an elevation in the plasma insulin/glucose ratio or a relationship between the insulin/glucose ratio and hemoglobin concentration at any time period. Plasma total glutathione concentration, however, decreased dramatically from the initial to the second transfusion (323 +/- 114 to 43 +/- 9 ng/ml; t = -5.06, p less than 0.01). We speculate that intrauterine transfusion may modify or prevent the previously reported fetal pancreatic beta-cell hyperplasia and hyperinsulinemia associated with isoimmunization by decreasing red blood cell hemolysis and thereby circulating glutathione. PMID- 1750470 TI - Does the brachial artery Doppler flow velocity waveform reflect changes in downstream impedance? AB - Brachial artery Doppler flow velocity waveforms were recorded from 10 nonpregnant women and 19 women with uncomplicated pregnancies. The pregnant group showed higher peak systolic frequencies (3.24 compared with 2.26, p = 0.01), higher maximum end-diastolic frequencies (0.62 compared with 0.25, p = 0.01), and lower pulsatility indices (2.57 compared with 3.95, p = 0.06) when compared with the nonpregnant group. These Doppler changes could reflect the increase in maternal cardiac output and decline in systemic vascular resistance that occur in normal pregnancy. The effect on brachial artery Doppler of acutely increasing downstream impedance by hand immersion in ice-cold water was studied in nine women with uncomplicated pregnancies at 32 to 38 weeks' gestation. Immersion for 15 seconds was associated with a significant reduction in peak systolic frequencies (from 3.06 to 1.97, p less than or equal to 0.005) and maximum end-diastolic frequencies (from 0.82 to 0.03, p less than or equal to 0.005) and a significant increase in the pulsatility index (from 1.87 to 5.62, p less than or equal to 0.005). These changes persisted for the duration of immersion (60 seconds). After immersion, the brachial artery flow velocity waveform returned to its preimmersion pattern by 60 seconds. We conclude that in normal pregnancy, the maternal brachial artery Doppler flow velocity waveform reflects acute and chronic changes in downstream impedance. PMID- 1750471 TI - Effect of pregnancy on the accuracy of light-reflection rheography. AB - Light-reflection rheography is a noninvasive method to detect venous obstruction by indirectly measuring venous emptying time. In nonpregnant women it has greater than 90% sensitivity when compared with venography but has not been tested during gestation. To determine if the nonthrombotic occlusion of venous outflow by the pregnant uterus might alter the performance of light-reflection rheography, we examined 17 normal patients with a vascular Accuscan (Hemodynamics, Inc., Boca Raton, Fla.) in the third trimester of pregnancy and 11 patients during the early second trimester. These results were compared with the defined normal (nonpregnant) rate of venous emptying (slope 0.54 +/- 0.06). The mean (+/- SD) for the entire sample was 0.58 +/- 0.23 mm/sec in the right leg and 0.52 +/- 0.19 mm/sec in the left leg measured in the standard sitting position (p = 0.21). The results did not vary with gestational age. A subset of patients in late pregnancy were used to compare the effect of various positions (supine, lateral decubitus, and sitting) on test performance. Positions other than sitting provided results that were inconsistent. It appears that the large pregnant uterus does not significantly obstruct venous outflow from the lower extremities in the standard sitting position; thus the results of light-reflection rheography are not affected. Comparison of light-reflection rheography versus venography in pregnant patients with suspected venous thrombosis is being investigated. PMID- 1750472 TI - Anticardiolipin antibody-positive serum enhances endothelial cell platelet activating factor production. AB - Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis. PMID- 1750473 TI - Combination antibiotics and indomethacin in idiopathic preterm labor: a randomized double-blind clinical trial. AB - Subclinical infection may play a role in the failure of magnesium sulfate tocolysis. Using a double-blind randomized study design, we administered a combination of ampicillin-sulbactam and indomethacin or corresponding placebos to patients in preterm labor who were receiving intravenous magnesium sulfate tocolysis. The mean gestational age at enrollment was 30.1 weeks, and mean cervical dilatation was 2.15 cm. No differences were noted between placebo (n = 43) and study patients (n = 43) in gestational age at delivery, term deliveries, days gained, or neonatal outcome. Preterm delivery (less than 36 weeks) occurred in 61% of the total population. The likelihood of a beta error was 0.07 to 0.23 on the basis of outcome analysis. In our population adjunctive ampicillin sulbactam with indomethacin did not improve the success of magnesium sulfate tocolysis. PMID- 1750474 TI - Dose-related action of gonadotropin-releasing hormone on basal prostanoid production from the human term placenta. AB - The dose-related effect of gonadotropin-releasing hormone on placental prostanoids was studied with a perifusion system. Villous tissues were perifused with medium 199 (1 ml/hr) and at the beginning of the fifth hour, either 0, 10( 10), 10(-9), 10(-8), 10(-7), or 10(-6) mol/L gonadotropin-releasing hormone was added to the medium of triplicate chambers. The concentration of prostaglandin E, prostaglandin F, 13,14-dihydro-15-keto-prostaglandin F2 alpha, 6-keto prostaglandin F1 alpha, and thromboxane B2 in the effluent medium, collected every hour, was determined by specific radioimmunoassay. The cumulative release after gonadotropin-releasing hormone treatment for each chamber was calculated, and replicate chambers were averaged. Linear regression analysis of the average for each dose from three different placentas was used to determine the dose response relationship. Gonadotropin-releasing hormone significantly inhibited the release of placental prostaglandin E, prostaglandin F, and thromboxane B2 in a dose-dependent fashion. Gonadotropin-releasing hormone had no significant effect on 13,14-dihydro-15-keto-prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha, although there was an apparent increase in 13,14-dihydro-15-keto prostaglandin F2 alpha. These data support the hypothesis that chorionic gonadotropin-releasing hormone inhibits prostanoid production from the placenta, which in turn may regulate various functions of prostanoids during pregnancy. PMID- 1750475 TI - Circadian myometrial and endocrine rhythms in the pregnant rhesus macaque: effects of constant light and timed melatonin infusion. AB - Six chronically catheterized rhesus macaques maintained on a 12-hour-light/dark cycle (lights on from 7 AM to 7 PM) showed a nocturnal uterine activity rhythm with peak contractile events between 9 and 11 PM (p less than 0.05). In blood samples collected at 3-hour intervals over a 24-hour period, we determined that plasma melatonin and progesterone concentrations were elevated at night whereas estradiol, estrone, and cortisol reached peak concentrations in the early morning (p less than 0.05). Lights were then left on for the remainder of the study. After 12 days in constant light, daily rhythms in uterine activity and plasma steroid levels were relatively unchanged, whereas melatonin concentrations were suppressed. Animals then received a timed infusion of melatonin (0.2 mg/kg/hr each day from 7 PM to 6 AM daily until delivery). The nocturnal uterine activity rhythm and the rhythms in plasma steroid concentrations were maintained. We conclude that the 24-hour patterns in maternal uterine activity and plasma steroid hormone levels are circadian rhythms generated by an endogenous biologic clock and do not appear to be driven by the pattern of melatonin in circulation. PMID- 1750476 TI - Effects of intravenous cocaine on reproductive function in the mated rabbit. AB - A dramatic increase in the use of crack cocaine by young women has resulted in the exposure of a substantial number of fetuses to the drug in utero. The goal of these experiments was to investigate the effects of intravenous cocaine (a model for crack) on reproductive function in the female rabbit. We used two protocols: (1) single daily injections over the course of pregnancy ("single daily" protocol), with animals examined on day 1, 8, 15, 22, or 29, and (2) six hourly injections on the day of mating ("binge" protocol). The maximum tolerated dose of cocaine, 4 mg/kg, was administered at 0.5 ml/min. The single daily protocol increased ovulation but had no effect on fetal and placental weights or preterm delivery. The binge protocol significantly reduced in vitro development of retrieved embryos but did not affect implantation assessed on day 8 of pregnancy. PMID- 1750477 TI - Expression of extracellular matrix-degrading metalloproteinases by cultured human cytotrophoblast cells: effects of cell adhesion and immunopurification. AB - In vitro, invasion of basement membrane by human trophoblast can be blocked by metalloproteinase inhibitors. The purpose of our study was to characterize these enzymes by zymography, to define their cellular origin. First-trimester cytotrophoblast cells were prepared according to the method of Kliman et al. Half of the cell suspension was further purified with an antibody to leukocyte common antigen (CD45). Cytotrophoblast cells (immunopurified or not) were incubated in Dulbecco's modified Eagle's medium on different matrices. Progesterone, total human chorionic gonadotropin, and free beta-human chorionic gonadotropin were measured in the supernatant by radioimmunoassay or enzyme immunoassays. Secreted (in the medium) and cell-bound proteases were characterized by zymography on sodium dodecyl sulfate-polyacrylamide gels containing gelatin. Cytotrophoblast cell preparations contained 12% to 34% leukocyte common antigen-positive cells before and 0% after immunopurification. Large zones of digested matrices were observed after 48 hours of culture on Matrigel or rat tail collagen but not on agarose. Cells secreted progesterone, human chorionic gonadotropin, and free beta human chorionic gonadotropin in vitro, but no difference was observed among cells grown on different matrices or between immunopurified and nonimmunopurified cells. By zymography, seven gelatin-degrading enzymes were seen in culture supernatants and five of them were present in cell lysates. The molecular weights of these proteases ranged from 59 to 230 kd. Immunopurification eliminated three of these enzymes, so they were clearly produced by bone marrow-derived cells (leukocyte common antigen positive) contaminating the cytotrophoblast cell preparation. Cells grown on Matrigel express a unique 59 kd gelatinase that was not seen in the supernatants of cells grown on other matrices. Zymography in the presence of inhibitors showed that these enzymes were neutral metalloproteinases, which might be responsible for the observed extracellular matrix degradation. PMID- 1750478 TI - Improvement of in vitro fertilization and early embryo development in mice by coculture with human fallopian tube epithelium. AB - Coculturing one- and two-cell embryos with various cell lines has been shown to overcome species-specific developmental blocks and to improve blastocyst transformation rates. The objective of this study was to assess whether human fallopian tube epithelium organ explants influence in vitro fertilization and subsequent early embryo development in a murine model. Fertilization, blastocyst transformation, and blastocyst expansion and hatching rates were significantly higher in the coculture group when compared with rates for culture in standard media or media conditioned by human tubal explant cultures. The results from conditioned and unconditioned media were not significantly different. PMID- 1750479 TI - Comparison of intermittent and continuous use of a gonadotropin-releasing hormone antagonist (Nal-Glu) in in vitro fertilization cycles: a preliminary report. AB - The agonistic effect of the gonadotropin-releasing hormone agonist often necessitates an extended period of treatment, resulting in a longer treatment cycle and increased cost. We have evaluated the intermittent use of a gonadotropin-releasing hormone antagonist, Nal-Glu, and have designed a new, simplified protocol for its use in in vitro fertilization. Seven women who had previously undergone treatment with leuprolide acetate and human menopausal gonadotropins were treated with Nal-Glu. Leuprolide acetate, 1 mg/day subcutaneously, was administered in the midluteal phase until down regulation was achieved (estradiol less than 30 pg/ml). Human menopausal gonadotropins, three to four ampules per day intramuscularly, was administered in conjunction with 500 micrograms subcutaneous leuprolide acetate. In the treatment cycles Nal-Glu (50 micrograms/kg/day) was administered intramuscularly on cycle day 1 or 2 for 3 days to achieve down regulation. Human menopausal gonadotropins, three to four ampules intramuscularly, was then administered daily without the antagonist. Nal Glu was resumed when the follicles reached 14 to 16 mm and was continued until the day of human chorionic gonadotropin administration. Compared with leuprolide acetate-human menopausal gonadotropins cycles, the days required for down regulation with Nal-Glu were significantly shortened (20.6 +/- 4.1 vs 1.6 +/- 0.3 days, p less than 0.001), as was total cycle length (31.3 +/- 5.8 vs 11.0 +/- 1.0 days, p less than 0.01). The mean number of days of treatment with human menopausal gonadotropins, the mean number of ampules of human menopausal gonadotropins, peak estradiol levels, the number of oocytes, and the percent of oocytes fertilized were not statistically different. No luteinizing hormone surges were detected with Nal-Glu in serum or urine. Nal-Glu was well tolerated, and five pregnancies have resulted. We conclude that intermittent administration of Nal-Glu is highly effective in achieving down-regulation and blocking spontaneous luteinizing hormone surges. Compared with leuprolide acetate-human menopausal gonadotropins cycles, an equally high oocyte and embryo yield may be anticipated. This new protocol substantially decreases cycle length and increases patient convenience. PMID- 1750480 TI - The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women. AB - The gonadotropin-releasing hormone antagonist offers several advantages over the use of the agonist and allows several physiologic questions to be addressed. In this study, we evaluated the ability of Nal-Glu to acutely inhibit the luteinizing hormone surge and prevent ovulation. We also assessed whether recovery of the follicle would be possible after several days of gonadotropin deprivation and estradiol decrement. Eight normal ovulatory women were randomized to control or Nal-Glu-treated cycles (50 micrograms/kg intramuscularly) for 3 to 4 days. Monitoring was carried out with daily vaginal ultrasonographic scans and serum estradiol levels and twice-daily serum luteinizing and follicle-stimulating hormone levels. Nal-Glu acutely inhibited the luteinizing hormone surge and ovulation, even when administered as late as the onset of the luteinizing hormone surge. Evidence was provided that spontaneous follicular rescue recurred in eight of 10 cycles after 3 to 4 days of Nal-Glu administration. Although an estradiol to follicular size dissociation occurred with Nal-Glu, subsequent ovulation occurred in 5.1 +/- 0.6 days after the last Nal-Glu dose. The decrement in estradiol after Nal-Glu administration correlated negatively with the days required for subsequent ovulation to occur (r = 0.77, p less than 0.05). The subsequent luteal phase also was normal in terms of length and progesterone levels. These data confirm the potency and efficacy of Nal-Glu in acutely inhibiting gonadotropins and extends our knowledge on the physiologic characteristics of the dominant follicle. PMID- 1750481 TI - The effect of the menstrual cycle and of decompression stress on arachidonic acid induced platelet aggregation and on intrinsic platelet thromboxane production in women compared with men. AB - Menstrual cycle variations in platelet aggregation and thromboxane production in association with sex steroids have been reported. External stimuli such as decompression sickness have been associated with clotting activity changes, specifically, increased platelet aggregation. Differences in response of platelets from women and men, when subjected to such a stress, have been observed. This study evaluated the ability of washed platelets from women in the proliferative and secretory phases of the menstrual cycle to aggregate in response to arachidonic acid and the aggregation difference between washed platelets from women and men in response to decompression stress and arachidonic acid. Additionally, platelet thromboxane production differences between the assessed platelet populations were compared. Our results indicate no difference in platelet aggregability between phases of the menstrual cycle. A significant aggregation difference between platelets from women and men was noted. Platelets from women were more sensitive to arachidonic acid aggregation. These differences were not affected by decompression stress. No difference in thromboxane B2 production was noted between the platelet populations evaluated. PMID- 1750482 TI - Tryptophan and neutral amino acids in premenstrual syndrome. AB - An abnormality of the serotonin system may play a role in the genesis of the symptoms of premenstrual syndrome, especially those related to mood and appetite. Whole blood and platelet uptake of serotonin are decreased during the luteal phase in women with premenstrual syndrome. The ratio of L-tryptophan (the amino acid precursor of serotonin) to the sum of the other neutral amino acids that compete for the same protein carrier cerebral uptake mechanism has been suggested to reflect central L-tryptophan levels and resultant serotonin levels in the brain. We evaluated the ratio of plasma L-tryptophan to the sum of five competing neutral amino acids in women with premenstrual syndrome and in controls. There were no significant differences between groups or across time, suggesting that it is unlikely that the aberrations of the serotonergic system in women with premenstrual syndrome are due to saturation of the tryptophan-carrying protein. PMID- 1750483 TI - The role of prostaglandins in detrusor instability. AB - To study the role of prostaglandin production by detrusor muscle in women with idiopathic primary detrusor instability, biopsies of detrusor muscle were obtained from 20 women. Nine women had detrusor instability, and 11 women had stable bladders. Prostaglandin F2 alpha and the stable metabolites of prostacyclin and thromboxane A2, namely, 6-keto-prostaglandin F1 alpha and thromboxane B2, respectively, were measured after in vitro incubations of detrusor muscle for 3 hours. A significant reduction in the production of 6-keto prostaglandin1 alpha in women with detrusor instability was noted. There were no differences in the production of prostaglandin F2 alpha and thromboxane B2, between women with stable and unstable bladders. These results suggest for the first time that women with idiopathic primary detrusor instability may have a deficient production of prostacyclin. PMID- 1750484 TI - Effects of peritoneal macrophages from patients with endometriosis on the proliferation of endometrial carcinoma cell line ECC-1. AB - Endometriosis has been shown to be associated with increased number and activity of peritoneal macrophages. The peritoneal macrophage-conditioned media from 33 women with or without endometriosis were studied for their effects on an endometrial carcinoma cell line, ECC-1. The media from six of six stage III/IV cases demonstrated a mitogenic effect, which was blocked by an antibody to epidermal growth factor receptor. However, the conditioned media from seven of nine stage I/II cases and 14 of 18 normal women did not show a mitogenic effect. The difference between stage III/IV and the other two groups was significant (p less than 0.01). The incorporation of tritium-thymidine was three times higher with the media from stage III/IV cases, as compared with that of controls. When purified cytokines were tested in the tritium-thymidine uptake assay, only epidermal growth factor-transforming growth factor-alpha was mitogenic on ECC-1, whereas tumor necrosis factor, interleukin-1, and platelet-derived growth factor had no effect. Thus peritoneal macrophages in patients with endometriosis may play an important role in the progression of endometriosis, and the noted effects could be mediated by epidermal growth factor or a related growth factor. PMID- 1750485 TI - Prolonged clearance of intraperitoneal 16 alpha-[125I]iodo-17 beta-estradiol in presence of ascites. AB - Radioestrogens have potential as adjunct therapeutic agents against ovarian carcinoma, because selected radionuclides can deposit lethal doses of radiation to tumor cells and many ovarian carcinomas and their metastases express estrogen receptors. Because intraperitoneal administration is a possible approach, we investigated absorption from the peritoneal cavity of a radioiodoestradiol after intraperitoneal application in rats with and without ovarian tumors and ascites and compared the distribution of the radioactivity with that obtained after intravenous injection. In the absence of ascites, 70% of the intraperitoneal dose was cleared into the intestine within 2 hours after injection, indicating fast absorption from the peritoneal cavity. In the presence of ascites, clearance of intraperitoneal radioiodoestradiol was considerably slower; at 2 hours after injection, 50% of the injected dose remained in the ascites, mostly as radioiodoestradiol. Uptake of radioactivity in estrogen receptor-rich tissues, e.g., uterus, after intraperitoneal injection was high (about 20:1 over blood), regardless of the presence of ascites, but moderately lower than that observed after intravenous injection of radioiodoestradiol. PMID- 1750486 TI - Increased progesterone concentrations are necessary to suppress interleukin-2 activated human mononuclear cell cytotoxicity. AB - Fetal trophoblast is generally resistant to lysis by cytotoxic cells. Trophoblast progesterone and estrogens may act at the choriodecidual interface, where they are present in high concentrations to provide a local, paracrine immunosuppressive effect on cellular cytotoxicity. However, interleukin activation of these cytotoxic lymphocytes enhances their ability to lyse trophoblast. Recent evidence suggests that immunoactivation occurs in certain aberrant pregnancy conditions, including preeclampsia. Preeclamptic placentas produce more progesterone in vitro than do normal placentas. To study the potential association between progesterone production and immunoactivation, we evaluated the immunomodulatory effect of progesterone on cellular cytotoxicity. Comparisons were made with the use of both normal and interleukin-2-stimulated peripheral blood mononuclear cells as effector cells in a cytotoxicity assay. Progesterone suppressed cytotoxicity in a dose-dependent manner. Interleukin-2 augmented cellular cytotoxicity, and higher concentrations of progesterone were required to attenuate this response. An additive suppression of cytotoxicity was also observed when estrone, estradiol, estriol, and progesterone were combined. We speculate that the higher placental production of progesterone seen in preeclampsia may be a trophoblast compensatory response to immunoactivated maternal effector cells. PMID- 1750487 TI - Sister chromatid exchange frequency in directly prepared cytotrophoblasts: demonstration of in vivo deoxyribonucleic acid damage in pregnant women who smoke cigarettes. AB - Assessing frequency of sister chromatid exchange is a sensitive method of monitoring exposure to clastogens, mutagens, and other substances that induce deoxyribonucleic acid damage. Aware that cigarette smoke is associated with increased sister chromatid exchange in many cell types, we sought to determine whether an in vivo effect of cigarette smoke could be demonstrated by study of sister chromatid exchange in chorionic villus cells. Directly prepared cytotrophoblasts and cultured mesenchymal core cells were analyzed. Mean sister chromatid exchange frequency in cytotrophoblasts from smoking subjects (8.87 sister chromatid exchanges per cell) was significantly greater than in nonsmoking subjects (5.81 sister chromatid exchanges per cell; p less than 0.001); however, no significant difference in cultured mesenchymal core cells was found. Our results demonstrate that maternal exposure to cigarette smoke results in direct placental deoxyribonucleic damage, which in turn could explain deleterious effects of smoking on pregnancy. Increased sister chromatid exchange frequency was observed only in directly prepared cytotrophoblasts, showing the necessity of using this cell type to evaluate the effects of clastogens on placentas. PMID- 1750488 TI - Cellular localization of mullerian inhibiting substance messenger ribonucleic acid during human ovarian follicular development. AB - Mullerian inhibiting substance is expressed in the human reproductive system and has been associated with oocyte meiotic arrest. In situ hybridization was used to selectively localize ovarian cells containing high levels of mullerian inhibiting substance messenger ribonucleic acid, a mullerian inhibiting substance precursor, during different stages of human follicular development. Mullerian inhibiting substance transcript was noted in the granulosa cells of primordial, primary, and antral follicles. Surprisingly, transcript was also identified within the cytoplasm of oocytes and throughout the ovarian stroma. Controls included sense oligoprobe, positive and negative tissue controls, and treatments minus the detection antibody. Localization of transcript within the cytoplasm demonstrates that active transcription of mullerian inhibiting substance messenger ribonucleic acid occurs within both fetal and adult human female gonads. The presence of mullerian inhibiting substance messenger ribonucleic acid within oocyte cytoplasm could implicate an autocrine role for mullerian inhibiting substance-derived peptides in the establishment of oocyte competence. PMID- 1750489 TI - The presence of the testicular determining sequence, SRY, in 46,XY females with gonadal dysgenesis (Swyer syndrome). AB - Subjects with 46,XY gonadal dysgenesis (Swyer syndrome) have a distinctive phenotype. They are normal or tall in stature, lack somatic anomalies, and possess bilateral rudimentary gonads. Critical Yp deletions have been described in some cases, but in the majority no defects at the molecular level have been reported. To verify the presence or absence of SRY, the putative testicular determining factor gene, specific primers were designed to amplify the conserved region of the SRY gene. Deoxyribonucleic acid from control males (n = 10) and sex reversed females with the Swyer syndrome phenotype (n = 5) generated the anticipated 310 bp band. This Y-specific band was absent in the deoxyribonucleic acid from control females (n = 9). To search for possible point mutations, the amplified products of all study subjects and one control male were sequenced in both orientations. The base pair sequences were all identical and similar to the previously published report. PMID- 1750490 TI - Evidence for a partial deletion in the androgen receptor gene in a phenotypic male with azoospermia. AB - Androgen resistance is thought to vary phenotypically from a normal female to an infertile male. Previous evaluation of infertile males has been limited to androgen receptor-binding affinity. The androgen receptor gene has been isolated, cloned, and studied extensively in patients with complete androgen insensitivity syndrome, but no comparative data are available on infertile males. To address this matter, the androgen receptor gene was studied in seven azoospermic males by use of the polymerase chain reaction and Southern blot hybridization. A partial gene deletion was found in one patient. This study provides the first molecular evidence of an abnormality in the androgen receptor gene in a phenotypic male with azoospermia. PMID- 1750491 TI - Giacomello's observation and nuchal cords. PMID- 1750492 TI - Ethics in medical studies with human subjects. PMID- 1750493 TI - Factors affecting embryo implantation after human in vitro fertilization. PMID- 1750494 TI - The origin of brain lesions in survivors of twin gestations complicated by fetal death. PMID- 1750495 TI - First report: prenatal diagnosis of a true knot. PMID- 1750496 TI - The effect of amnioinfusion on uterine pressure and activity. PMID- 1750497 TI - Alternative estimates of ectopic pregnancy risks during contraception. PMID- 1750498 TI - First report: prenatal diagnosis of long cord. PMID- 1750499 TI - Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease. AB - Transforming growth factor (TGF) beta 1 has been implicated in the control of hepatocyte growth and stimulation of extracellular matrix synthesis in acute and chronic liver disease. The cellular localization of transforming growth factor (TGF) beta 1 and beta 2 RNA transcripts was determined in normal and fibrotic liver by in situ hybridization with [35S]-labeled RNA probes in combination with immunostaining for cell type characteristic markers. Fibrotic specimens were from patients with hepatitis B virus infection or alcohol abuse and rats with fibrosis secondary to bile duct ligation and scission. In normal liver, low levels of TGF beta 1 transcripts were found in some portal tract stromal cells, and TGF beta 2 RNA was not detectable. In fibrotic liver, high TGF beta 1 RNA levels were present in most mesenchymal liver cells, in most inflammatory cells, and in few bile duct epithelial cells. Hepatocytes did not express this cytokine with the exception of few limiting plate hepatocytes in cases of human cirrhosis with high activity. TGF beta 2 transcripts were detected at high levels in proliferating bile ducts of fibrotic livers, but were absent in all other cell types. TGF beta 1 expression in the liver is thus a function predominantly of mononuclear and mesenchymal cells as well as of some hepatocytes, whereas TGF beta 2 expression is a specific property of bile duct epithelial cells that may be related to the formation of specialized periductular connective tissue during bile duct proliferation. PMID- 1750500 TI - Absence of t(14;18) major and minor breakpoints and of Bcl-2 protein overproduction in Reed-Sternberg cells of Hodgkin's disease. AB - The t(14;18) translocation, found in most human follicular non-Hodgkin's lymphomas (NHLs), juxtaposes the Bcl-2 oncogene at 18q21 with the immunoglobulin heavy chain locus at 14q32. As a result, the Bcl-2 protein is markedly overproduced. Most of the breakpoints on chromosome 18 cluster at one of two sites, the major breakpoint region (mbr) and the minor cluster region (mcr). Recently, others used the polymerase chain reaction (PCR) to detect the t(14;18) mbr in 32% of specimens diagnosed as Hodgkin's disease (HD). In an attempt to confirm and extend those observations the authors used PCR to assay for both the mbr and mcr in HD specimens diagnosed at their institution and examined the specimens for Bcl-2 overproduction. The authors subjected the DNAs from 28 well characterized HD tumors of 26 patients to PCR analyses using primers specific for the t(14;18) mbr and mcr breakpoints. Based on various PCR controls, the authors ascertained that 26 of the 28 specimens contained amplifiable template DNA. Southern blotting of the amplification products showed that none of the 26 HD DNAs had detectable t(14;18) mbr or mcr breakpoints. By admixing small amounts of t(14;18)-bearing NHL DNA with HD DNA samples, the authors directly demonstrated that the sensitivity of the PCR assays was adequate for the molecular detection of t(14;18)-bearing cells at a frequency comparable to that of Reed-Sternberg cells and their variants in HD. Immunohistochemical studies employing a highly specific anti-Bcl-2 antiserum under conditions optimized to detect t(14;18) mediated overexpression of the Bcl-2 gene showed that the Reed-Sternberg cells and variants in all 19 HD tumors examined were negative for Bcl-2 immunostaining. In conclusion, the PCR and immunohistochemical data provided evidence that the t(14;18) translocation was not involved in the pathogenesis of the HD cases. PMID- 1750501 TI - AIDS-associated Kaposi's sarcoma-derived cells in long-term culture express and synthesize smooth muscle alpha-actin. AB - Spindle-shaped cells from Kaposi's sarcoma lesions (AIDS-KS cells) were cultured for long periods in the presence of conditioned medium from activated CD4 positive T cells (HTLV-II infected transformed nonvirus producer) and characterized under in vitro conditions. To investigate a possible vascular origin, AIDS-KS cells were analyzed for the presence of smooth muscle alpha actin, a differentiation marker for vascular smooth muscle cells. Immunofluorescence studies using a monoclonal antibody for smooth muscle alpha actin demonstrated positive staining of the AIDS-KS cells (KS-3 and KS-4) but not by endothelial cells or fibroblasts. Northern blot analysis using an oligonucleotide probe unique for human smooth muscle alpha-actin indicated the expression of this gene by AIDS-KS cells. Similar analysis of biopsies from the KS lesion showed that in addition to the staining of smooth muscle cells associated with the blood vessels, the tumor-related spindle cells also stained positively. These cells were also analyzed for the expression of different growth factor genes. The platelet-derived growth factor (PDGF) A-chain gene was expressed at a moderate level. The insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) genes were not overexpressed in relation to control cells. These data suggest that the analyzed AIDS-KS cells may be smooth muscle-like cells and therefore of vascular origin. Based on these results as well as previous reports, we speculate that cells of the immune system may regulate growth of cells in the vascular wall by a novel pathway. PMID- 1750502 TI - Myositis in mice inoculated with Borrelia burgdorferi. AB - The authors describe the appearance of myositis in immunocompetent and immunodeficient mice after subcutaneous inoculation with Borrelia burgdorferi by histology and immunohistology. Experimental infection of mice 1) causes inflammation of striated but not smooth muscles, 2) affects the entire musculoskeletal system, and 3) is characterized by perivascular and interfacicular infiltration of mononuclear leukocytes in the striated muscle leading to necrosis as well as disruption of muscle fibers. The lesions found in striated muscle specimens were most pronounced in immunodeficient (SCID), less severe in T-cell-deficient nu/nu (BALB/c, C57BL/6) and marginal to moderate or almost not present in immunocompetent AKR/N and C.B-17 mice, respectively. PMID- 1750503 TI - Early viral replication in the brain of SIV-infected rhesus monkeys. AB - To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express the CD68 marker, suggesting that infected mononuclear phagocytes crossing the blood-brain barrier represent the main source of virus in the CNS. Early viral replication coincided with neuropathologic changes, consisting in gliosis, perivascular infiltrates and rare glial nodules. Immunophenotyping of brain tissue showed that increased macrophage infiltration, microglial reactivity and MHC class II induction occurred within the first week of infection, indicating a possible immunopathologic mechanism in early CNS pathogenesis. PMID- 1750504 TI - Angiotensin-converting enzyme inhibitor versus angiotensin II, AT1 receptor antagonist. Effects on smooth muscle cell migration and proliferation after balloon catheter injury. AB - The angiotensin-converting enzyme (ACE) inhibitor, benazeprilat and the angiotensin II (Ang II), AT1-specific receptor antagonist, DuP753, were compared for their effects on intimal lesion formation as well as smooth muscle cell (SMC) proliferation and migration in Sprague Dawley rats after carotid balloon injury. Both the ACE inhibitor (benazeprilat, 3 mg/kg/day) and the AT1 antagonist (DuP 753, 10 mg/kg/day) significantly reduced intimal lesion formation after balloon injury (by 35% and 49%, respectively). Medial SMC proliferation after injury was reduced 53% by the AT1 antagonist; however, the ACE inhibitor had no effect on SMC proliferation. SMC migration was reduced 94% by the AT1 antagonist and 68% by the ACE inhibitor. These data demonstrate the importance of Ang II in SMC proliferation and migration after balloon injury. They also demonstrate that in the balloon injury model, the ACE inhibitor reduced intimal lesion size by inhibiting SMC migration alone without affecting SMC proliferation. A more pronounced reduction in lesion size was obtained after AT1 antagonism, however, when both SMC migration and proliferation were inhibited. PMID- 1750505 TI - HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit. AB - The monoclonal antibodies HML-1, B-ly7 and Ber-ACT8 recognize intramucosal gut T lymphocytes, activated cells, and hairy cell leukemia. The antigen on hairy cells consists of three glycoproteins (160 kappa D, 130 kappa D and 105 kappa D unreduced; 145 kappa D and 120 kappa D reduced). These peptides have biochemical features reminiscent of integrins but we have shown by immunoprecipitation that they are not known integrin subunits. We have used a newly produced antibody (BP6) to purify this molecule and shown by N-terminal sequence analysis that the smallest subunit is the product of integrin beta 7 cDNA. This molecule is thus a new member of the integrin family of leucocyte adhesion proteins. Immunoprecipitation experiments indicate that the two larger subunits are recognized by HML-1, B-ly7 and Ber-ACT8. PMID- 1750506 TI - Human lung-derived mature mast cells cultured alone or with mouse 3T3 fibroblasts maintain an ultrastructural phenotype different from that of human mast cells that develop from human cord blood cells cultured with 3T3 fibroblasts. AB - Culture systems designed to maintain or develop human mast cells have proved difficult, yet these systems would provide valuable resources for future investigations of human mast cell biology. Cocultures of either isolated mature human lung mast cells (Levi-Schaffer et al., J Immunol 1987, 139:494-500) or human cord blood mononuclear cells (Furitsu, Proc Natl Acad Sci USA 1989, 86:10039-10043) with 3T3 embryonic mouse skin fibroblasts have implicated fibroblasts as an important factor in the successful maintenance and development of human mast cells in vitro. The authors cultured isolated, mature human lung mast cells either with or without 3T3 cells for 1 month and examined their ultrastructural phenotype. Mast cell viability in each circumstance was equivalent, but mast cell yield was improved in the presence of 3T3 cells. The ultrastructural phenotype was identical in both culture systems. Mast cells were shown to maintain the phenotype of their in vivo lung counterparts (ie, scroll granules predominanted, and numerous lipid bodies were present). This ultrastructural phenotype differs from that of mast cells that develop in cocultures of human cord blood cells and 3T3 cells, where developing mast cells with crystalline granules and few lipid bodies prevail, a phenotype much like that of human skin mast cells in vivo (Furitsu, Proc Natl Acad Sci USA 1989, 86:10039-10043). PMID- 1750507 TI - Immunohistochemical localization of syndecan in mouse skin tumors induced by UV irradiation. Loss of expression associated with malignant transformation. AB - Immunoreactivity for syndecan, a cell surface proteoglycan, which binds extracellular matrix molecules and growth factors, was studied in hairless (hr/hr) mice exposed to UV-A and UV-B irradiation. Positive staining was observed at the surface of normal epidermal cells as well as in the dermal abortive hair follicle cysts characteristic to this mouse strain. Early reaction to UV irradiation showing hyperplastic epidermis with slight cellular atypia showed also positive, although reduced, staining of epidermal cell surfaces. Specimens with severe dysplasia showed weak staining in the granular cell layer, whereas the basal cell layer was negative. In papillomas and keratoacanthomas, immunoreactivity for syndecan was observed in the benign hyperplastic epidermal cells as well as in the proliferating epidermal cells of the horn cysts. Malignant transformation of epithelium, expressed as the formation of early invasive and anaplastic squamous cell carcinomas, was uniformly associated with loss of syndecan staining. These results are consistent with the previous findings of reduced expression of syndecan associated with malignant transformation of cultured epithelial cells, but also suggest an important role for syndecan in the maintenance of normal tissue architecture and differentiation pattern of the skin. PMID- 1750508 TI - Characterizations of and interactions between bile ductule cells and hepatocytes in early stages of rat hepatocarcinogenesis induced by ethionine. AB - Numerous hepatic cell lineage pathways have been proposed for the development of hepatocarcinogensis induced by chemical carcinogens in rats. The roles of bile ductule cells and hepatocytes in the development of carcinogenesis were investigated using light and electron microscopic procedures to detect differences in morphology and in the phenotypic expression of antigens that are associated with each cell type. In early stages of hepatocarcinogenesis (4-10 weeks after initiation of feeding of a choline-deficient ethionine containing diet), both bile ductulelike (BDL) cells and hepatocytes were seen in mitosis. At the light microscope level, BDL cells showed intense cytoplasmic pyronin (RNA) staining and were positive for the antigens defined by monoclonal antibody 270.38 (bile ductule cells and "oval" cell marker) and glutathione-S-transferase (Yp isoform), whereas hepatocytes were positive for the antigens defined by monoclonal antibodies 270.26 and 258.26 (liver parenchymal cell markers), catalase activity (peroxisome marker) and adenosine triphospatase activity (bile canalicular marker). The authors frequently encountered BDL cells and hepatocytes in close proximity. Ultrastructural examination showed extensive plasma membrane appositions between a subset of BDL cells and hepatocytes. Desmosome structures, tight junctions, microvilli interdigitations and ATPase-positive bile canalicularlike structures were present along the contiguous plasma membrane domains of BDL cells and hepatocytes. Many of the BDL cells attached to hepatocytes were also attached to other BDL cells that had retained a basal lamina. In many cases, BDL cells connected to both hepatocytes and other BDL cells were no longer completely surrounded by basal lamina and had acquired a dual polarity as a consequence of their sharing apical and lateral membrane domains with both BDL cells and hepatocytes. BDL cells showed increased numbers of microperoxisomes (catalase positive organelles) and numerous free ribosomes. Hepatocytes showed a prominent development of the smooth endoplasmic reticulum, a feature prominent in hepatocytes within hyperplastic nodules. Since BDL cells and hepatocytes proliferate and BDL cells and hepatocytes develop intercellular junction sites, the authors propose that both cell types in early stages of carcinogenesis have the capacity to enter the cell lineage pathway leading to the development of hepatocarcinoma. Furthermore, the finding that BDL cells and hepatocytes form multiple attachment sites at the level of the plasma membrane, suggests the possibility that at some stage convergence of separate hepatic cell pathways may occur. PMID- 1750509 TI - Differential expression of basement membrane collagen in membranous nephropathy. AB - Membranous nephropathy (MN) is characterized by subepithelial immune complex formation and progressive thickening of the glomerular basement membrane (GBM). Kidney tissues from 21 patients stratified according to morphology (stage I: 5 patients; stage II: 5 patients, stage III: 11 patients) were studied by immunohistochemical techniques using antibody probes to matrix components of recently described (novel) chains of type IV collagen [alpha 3(IV)NC, alpha 4(IV)NC, Alport antigen] and of traditional type IV collagen [alpha 1(IV)NC, alpha 2(IV)NC, 7S(IV), triple helix]; as well as laminin B2, nidogen and fibronectin. In Stage I, there were no detectable changes when compared with normal tissue. In Stage II and early Stage III, the subepithelial projections of GBM (spikes) and the thickened GBM consisted predominantly of the novel type IV collagen chains as well as laminin B2 and nidogen, with no detectable changes in traditional type IV collagen. In late Stage III, an increase in the latter was observed in the subendothelial region of the thickened GBM with narrowing of the capillary lumen. At this stage, there was close apposition of novel and traditional type IV collagen molecules. The expression of these two groups of molecules is spatially and temporally distinct during the evolution of MN. It is hypothesized that immune complex formation in the subepithelial region of the GBM leads to increased formation of the novel type IV collagen network by visceral epithelial cells resulting in the formation of spikes and thickening of GBM between and surrounding immune deposits. These changes precede and are distinct from detectable alterations in traditional type IV collagen. With progression and time, the deposits become embedded in the novel collagen network and increased subendothelial formation of traditional type IV collagen molecules occurs with narrowing of the capillary lumen. PMID- 1750510 TI - Central nervous system endothelial cell-polymorphonuclear cell interactions during autoimmune demyelination. AB - The homing and adhesion of circulating cells to target tissue vasculature precedes their subsequent invasion of inflamed tissue. Polymorphonuclear cells (PMNs), key players in most inflammatory events, are among the first cells to arrive. The present work, performed on CNS lesions from mice with experimental autoimmune encephalomyelitis, provides morphologic evidence for interactions between PMNs and unique, frondlike extensions from endothelial cells (EC) during early attachment. Platelets also were seen attached to these endothelial fronds. The structures projected into vessel lumina from the vicinity of tight junctions and were often branched and complex, the latter characteristics suggesting a possible role in cellular 'trapping'. Polymorphonuclear cells appeared to traverse the CNS vasculature between EC where the blood-brain barrier was severely compromised with junctional complexes reduced to simple contact points. The cells from which the fronds derived were often plump and possessed cytoplasm rich in organelles, perhaps indicative of activation. The present report contrasts with previous observations on lymphocytes in the same system where lymphocytic pseudopodia formed intimate contacts before their burrowing directly through the endothelium and where EC fronds were not involved. PMID- 1750511 TI - Tissue distribution, intracellular localization, and in vitro expression of bovine macrophage scavenger receptors. AB - Macrophage scavenger receptors are trimeric membrane proteins implicated in the pathologic deposition of cholesterol in atherogenesis. The authors have studied the tissue distribution and intracellular localization of bovine scavenger receptors using monoclonal antibovine receptor antibody IgG-D2. The receptor proteins were detectable in macrophages of various organs and tissues, particularly Kupffer cells, alveolar macrophages, and macrophages in the spleen and lymph nodes. In the brain, perivascular macrophages were immunoreactive with IgG-D2. Fibroblasts, endothelial cells, smooth muscle cells, and dendritic cells such as epidermal Langerhans cells, interdigitating cells, or follicular dendritic cells, however, showed no immunoreactivity to IgG-D2. Immunoelectron microscopy showed localization of reaction products for these receptors on the cell surface, vesicles, and endosomes of macrophages. Transient expression of bovine scavenger receptors on cultured cells shows that scavenger receptors are mainly expressed in the endoplasmic reticulum, nuclear envelope, and Golgi apparatus of nonmacrophage cells and moved to the cell surface and endosomes of macrophagelike cells. These results indicate that efficient intracellular transport of scavenger receptors in macrophages is mediated by a macrophage specific transport system. PMID- 1750512 TI - Iron translocation by free fatty acids. AB - Organic extracts of cigarette smoke and uncombusted tobacco contain substances capable of translocating iron from aqueous solutions into immiscible organic solvents. Such extracts will also effect the organic solvation of iron present in ferruginous forms of asbestos such as amosite and crocidolite (Qian and Eaton, Arch Biochem Biophys 1989, 275:280). These substances, previously detected by their iron-translocating properties, have now been purified and identified by mass spectroscopy as saturated fatty acids, predominantly stearic and palmitic acids. Organic extracts of tobacco smoke, as well as the pure fatty acids, also transfer ferrous iron into both isolated red cell membranes and intact human erythrocytes. The increased membrane iron may enhance cellular susceptibility to exogenous oxidants; erythrocyte membranes subject to fatty acid-mediated iron accumulation show elevated peroxidation of endogenous polyunsaturated fatty acids. These observations may help explain the phlogistic effects of tobacco use and suggest, in a broader context, that free fatty acids may act as physiologic and pathologic mediators of metal translocation. PMID- 1750513 TI - Heterogeneous distribution of Weibel-Palade bodies and von Willebrand factor along the porcine vascular tree. AB - Vessels obtained from different levels of pig vascular tree were examined by transmission electron microscope, with the aim of determining whether or not their endothelial cells contain Weibel-Palade bodies (WPB). As these organelles are known to store the von Willebrand factor (vWF), a two-step immunogold labeling of this protein also was performed. Our results showed for the first time a heterogeneous distribution of WPB along the vascular tree of the normal pig: These structures were absent from the thoracic aorta, rare in the abdominal aorta, present in myocardial capillaries, and numerous in the inferior vena cava and pulmonary artery. Atypical WPB devoid of tubules were seen in all endothelial cells. The ultrastructural labeling of vWF demonstrated its presence only in the WPB, being absent in the subendothelium, and showed the same variation in its distribution along the vascular tree as for its storage organelle. Pigs homozygous for the von Willebrand disease were found to have only the atypical WPB, and do not express the vWF. PMID- 1750514 TI - Repeated exposures to enzyme-generated oxidants cause alveolitis, epithelial hyperplasia, and fibrosis in hamsters. AB - Oxidant-mediated epithelial injury and repair processes may promote the development of pulmonary fibrosis. The authors examined this hypothesis by inducing oxidant injury in hamsters with intratracheally instilled mixtures of glucose, glucose oxidase (GO) and lactoperoxidase at weekly intervals. Solutions containing denatured GO (DE) served as a control treatment. One and six days after each treatment, anesthetized animals were sacrificed and lavaged, and their lungs and plasma were preserved for further study. Although DE-treatment consistently evoked a transient, neutrophil-rich inflammatory response, no significant biochemical or morphologic changes were detected at the ensuing 6-day time points. In contrast, repeated GO treatments prolonged inflammation and injured the alveolar epithelium, evidenced by significantly greater levels of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and increased BALF levels of protein, beta-glucuronidase and lactic dehydrogenase activities. Active GO also altered BALF lymphocytes and monocytes, but no discernable pattern emerged. Fibrotic, consolidated parenchyma appeared after the second and third GO exposures, coinciding with increased levels of total collagen, prolyl hydroxylase activity, and anti-oxidant enzyme activities. Although alveolitis and type II cell hyperplasia were observed after the initial treatment, polyplike nodules covered by hyperplastic, undifferentiated epithelium were evident after the third treatment. After each exposure, GO-treated animals had larger volumes of parenchymal lesion than DE-treated hamsters. These data indicate that normal alveolar epithelial repair processes were greatly disrupted by repeated oxidant injury and suggest that repeated and/or continued epithelial injury may contribute to the development of pulmonary fibrosis. PMID- 1750515 TI - Antiproliferative effects of novel, nonanticoagulant heparin derivatives on vascular smooth muscle cells in vitro and in vivo. AB - The proliferation of vascular smooth muscle cells (VSMC) is strongly inhibited by whole heparin both in vitro and in vivo. To identify and characterize antiproliferative, but nonanticoagulant heparin derivatives, heparin fragments made by periodate treatment were produced and acylated with 2-, 4-, or 6-carbon chain lengths. In culture, the 4- and 6-carbon acylated compounds were more effective than whole heparin in inhibiting serum stimulated VSMC growth at equal mass or approximately equal mean molar concentrations. Further testing was performed in the rat carotid balloon injury model. Myointimal VSMC proliferation produced by balloon catheterization of rat carotid arteries was inhibited by the 4-carbon acylated compound as effectively as heparin at the same mass dose. Importantly, unlike heparin, the 4-carbon acylated compound had no anticoagulant effect in vivo. These experiments suggest nonanticoagulant, acylated heparin derivatives may have a pharmacologic role in preventing myointimal proliferative lesions that are responsible for failures of vascular surgeries and angioplasties. PMID- 1750516 TI - Ovine GM-1 gangliosidosis. PMID- 1750517 TI - Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure. AB - The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg 1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect. PMID- 1750518 TI - Coupled water transport by rat proximal tubule. AB - Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to examine water reabsorption by this epithelium. Osmolality of the luminal solution was varied with changes in NaCl concentration and by the addition of raffinose. Capillary perfusates contained either low (2 g/dl) or high (16 g/dl) concentrations of albumin. We used low-bicarbonate perfusates for both lumen and capillary so that we might apply the nonequilibrium thermodynamic model of transport for a single solute (NaCl) to interpret our observations. Linear regression with the volume flux equation Jv = -Lp delta II - Lp sigma delta C + Jav (where Jv is volume flux, Lp is hydraulic conductance, delta II is oncotic force, sigma is osmotic reflection coefficient, delta C is salt concentration difference, and Jav is the component of Jv not attributed to transepithelial hydrostatic or osmotic forces) revealed a tubule water permeability (Pf = 0.11 +/- 0.01 cm/s) and a sigma (0.74 +/- 0.08) in agreement with previous determinations. These transport parameters were unaffected by changes in peritubular protein. We also found that Jav was substantial, approximately three-fourths of the rate of isotonic transport under these perfusion conditions. Further, this component of water transport nearly doubled with the transition from low- to high-protein peritubular capillary perfusion. When expressed as a capacity for water reabsorption against an osmotic gradient, the salt concentration differences required to null volume flux were 13.2 +/- 2.4 and 29.4 +/- 4.0 mosmol/kgH2O under low and high peritubular protein. Our data suggest that this protein effect is, most likely, an increase in solute transport by the tubule epithelial cells. PMID- 1750519 TI - Localization of ral, a small Mr GTP-binding protein, to collecting duct cells in bovine and rat kidney. AB - Plasma membranes from bovine kidney cortex were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose membranes. Blotting with [alpha-32P]GTP and [35S]GTP gamma S demonstrated specific binding to three and six distinct protein bands, respectively, in the 20,000- to 29,000-Mr range. This indicated the presence of small Mr GTP binding proteins (smg) in bovine kidney cortex. Only one smg with 28,000 Mr was labeled with hydrolysis-resistant GTP photoaffinity probe p3-(4 azidoanilido)-p1-5GTP (AAGTP). The major smg in platelet membranes that binds GTP on nitrocellulose blots has been identified as ral-Mr 29,000. With the use of an antiserum against the ral A gene product, one of the smg with Mr of 29,000 present in bovine renal cortical plasma membranes was identified as ral. Ral was absent from glomerular homogenate, suggesting that it is localized to the tubular segments of the nephron. Ral was detected only in the particulate fraction and not the cytosol. Further subcellular localization of ral was investigated by immunohistochemical staining. Anti-ral antibody immunostained the apical and basolateral membranes of cells in the cortical and medullary collecting ducts in a speckled pattern in the bovine kidney. In the rat kidney, however, uniform linear staining of cortical and medullary collecting ducts predominantly localized to the apical membrane was observed. To date, no function has been assigned to ral. Localization of the ral gene product to the collecting duct suggests a specific functional role for this GTP-binding protein. PMID- 1750520 TI - Expression of cytokine-like genes JE and KC is increased during renal ischemia. AB - Both mitogenic and inflammatory phenomena accompany the renal response to ischemic injury. Previous studies have shown that several nuclear-binding members of the immediate early genes are prominently expressed after renal ischemia and may underlie the mitogenic response to such injury. We now report on the expression of JE and KC, other growth-factor-responsive genes that code for small secreted glycoproteins with cytokine-like properties, which may play a role in inflammation. The expression of the immediate early genes JE and KC was determined in rat kidney tissue at varying time points after release of a 50-min period of bilateral renal hilar clamping. Relative levels of mRNA for JE and KC were analyzed by Northern blot analysis of cortical and outer stripe mRNA. KC mRNA rose rapidly to peak values at 1 h and returned toward low baseline levels by 24 h after release of the hilar clamp. By contrast, JE mRNA reached peak levels later and remained elevated for at least 96 h after ischemia. JE antigen was localized immunocytochemically to the apical regions of the cortical and medullary thick ascending limbs as well as in the lumen of the distal nephron in ischemic kidneys. Cells of the glomerulus and proximal tubules were negative for JE antigen. In contrast to the increase in JE and KC mRNA, steady-state levels of uromodulin (Tamm Horsfall) mRNA, a cytokine binding protein also made by the thick ascending limb, declined to virtually undetectable levels by 24 h after ischemia. Thus the increases in JE and KC are not generalized phenomena.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750521 TI - Osmotically regulated taurine content in rat renal inner medulla. AB - During antidiuresis renal medullary cells were previously found to accumulate large amounts of organic osmolytes, namely sorbitol, myo-inositol, glycerophosphorylcholine (GPC), and betaine. Large quantities of amino acids are also present in the renal medulla, but it has been questionable whether the levels of medullary amino acids are osmotically regulated. Therefore we directly measured 26 different amino acids, as well as sorbitol, myo-inositol, GPC, and betaine alone the corticomedullary axis of rats that were either salt loaded, after infusion of hypertonic NaCl solution, or were hydrated, after infusion of hypotonic NaCl solution. The amounts of sorbitol, myo-inositol, GPC, and betaine are greater in the inner medullas of salt-loaded rats compared with hydrated rats. In addition, the amount of taurine is much greater in the inner medullas of salt-loaded rats. Aspartic acid also increases in salt-loaded rats but to a lesser extent. There are substantial gradients of taurine, aspartic acid, and some of 24 other measured amino acids along the corticomedullary axis. However, taurine and aspartic acid are the only measured amino acids that increase significantly during salt loading. PMID- 1750522 TI - Differing renal effects of activated and nonactivated isoelectric peaks of human prorenin in rats. AB - Isoelectric species of renin are physically heterogeneous. Recent evidence suggests that they may differ functionally, with some species producing natriuresis and diuresis, whereas others have no effect. A physiological function of secreted prorenin has not been documented in any species. The present study was designed to confirm and describe for the first time the renal effects of certain isoelectric species of prorenin. Anesthetized Sprague-Dawley rats were injected (0.1 ml) with trypsin-activated or nonactivated prorenin obtained from human ovarian follicular fluid. The dose chosen was calculated as sufficient to produce 2,300 ng angiotensin I.h-1.100 g rat body wt-1 in the presence of excess sheep substrate. Blood pressure, creatinine clearance, urine flow rate, and urine sodium, potassium, and osmolar excretion were measured. Activated prorenin from isoelectric peaks at isoelectric points (pI) 5.1, 5.2, 5.4, and 5.6 produced marked increases in urine volume (sixfold) and sodium excretion (7- to 10-fold) compared with the group receiving the vehicle (1% albumin in 0.9% saline). Activated prorenin from peaks at pI 4.9 and 5.8 produced no significant increase over the vehicle-only experiments. Captopril pretreatment (1 mg/kg iv) completely blocked the effects of peaks at pI 5.4 and 5.6. Interestingly, injection of nonactivated prorenin from peaks at pI 5.4 and 5.6 produced effects similar to the injection of activated prorenin from these peaks. Similarly, this effect was blocked by pretreatment with captopril. In summary, only certain isoelectric peaks of human prorenin whether activated, to active renin, or nonactivated produced a marked natriuresis and diuresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750523 TI - Effect of inhibitors of oxidative phosphorylation on erythropoietin mRNA in isolated perfused rat kidneys. AB - We have used RNase protection to measure oxygen-dependent changes in erythropoietin (EPO) mRNA in isolated perfused kidneys and to compare the effect of hypoxia with the response to inhibitors of oxidative phosphorylation. In well oxygenated kidneys perfused for 2 h at 12 ml/min, with hematocrit of 0.09 +/- 0.005 and PO2 of 443 +/- 67 mmHg, EPO mRNA levels were similar to the baseline levels measured in nonperfused contralateral kidneys from the same animals. When perfusions were performed under identical conditions but at a PO2 of 32 +/- 4 mmHg, EPO mRNA increased approximately 16-fold. In contrast, graded concentrations of cyanide (10, 100, and 300 microM and 1 mM), antimycin (0.01, 0.1, 0.5, and 1 microM), and oligomycin (0.01, 0.1, and 1 microM) did not alter EPO mRNA in well-oxygenated perfused kidneys. However, in kidneys perfused at low PO2 with a high concentration of each inhibitor, EPO mRNA levels were increased, demonstrating that the ability to respond to hypoxia was retained. Thus inhibitors of oxidative phosphorylation did not mimic the effects of hypoxia, indicating that oxygen-dependent expression of the EPO gene in the kidney is not effected through hypoxic compromise of oxidative phosphorylation. PMID- 1750524 TI - Kinetic analysis of clearance of epidermal growth factor in isolated perfused rat kidney. AB - Our previous in vivo studies identified the saturable uptake of epidermal growth factor (EGF) by rat kidney (D.C. Kim, Y. Sugiyama, H. Sato, T. Fuwa, T. Iga, and M. Hanano, J. Pharm. Sci. 77: 200-207, 1988). In the present study, renal handling of EGF in filtering and nonfiltering isolated perfused rat kidneys was investigated. At designated times after the recirculatory perfusion of 125I-EGF in the nonfiltering kidney, the surface-bound and internalized EGF were separately determined by an acid-washing technique. Time profiles of cell-surface bound and internalized EGF obtained at the perfusion of a tracer 125I-EGF were fitted to the pharmacokinetic model, and kinetic parameters obtained were as follows: konRs = 0.49 ml.min-1.g-1, koff = 0.87 min-1, kint = 0.20 min-1 where konRs is the binding clearance of EGF with its receptor and koff and kint represent the dissociation and internalization rate constants of the EGF-receptor complex, respectively. The Scatchard analysis of the concentration-dependent EGF binding in the nonfiltering kidney suggests the presence of two binding components, one with high affinity [the apparent dissociation constant (Kd1 = 0.1 nM) and the other with low affinity (Kd2 = 30 nM]. By comparing the internalization clearance (CLi) with filtering and nonfiltering kidneys, we concluded that the renal uptake of EGF occurs mainly from the antiluminal side via receptor-mediated endocytosis in a saturable manner and that the nonsaturable reabsorption of EGF from the luminal membrane after glomerular filtration is relatively small. The contribution of reabsorption, however, becomes larger with the increase in EGF concentration. PMID- 1750525 TI - Adenosine triphosphate-sensitive potassium channels in the cardiovascular system. AB - ATP is normally available in cells at millimolar concentrations and is "buffered" by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular [ATP] [( ATP]i) may seem an unlikely candidate for a regulatory signal inside cells. Recent evidence suggests, however, that [ATP]i regulates the behavior of a class of potassium (KATP) channels that are found throughout the cardiovascular system. KATP channels are present in cardiac, skeletal, and vascular smooth muscle. The channels are inhibited by micromolar [ATP]i, and this inhibition is relieved by micromolar [ADP]i. We present evidence in support of the idea that variations of [ATP]i and [ADP]i, even within normal concentration ranges, may influence cellular function in the heart and vascular system via a direct action on the KATP channel. Furthermore, very specific modulators of KATP channel activity are available. We discuss the mechanism of action of these agents and their interaction with endogenous modulators and consider their potential roles in cardiovascular therapy. PMID- 1750526 TI - Areas of rostral medulla providing tonic control of renal and splenic nerves. AB - The objective of this study was to determine whether nonuniform control of tonic discharge of renal and splenic nerves by the rostral ventrolateral medulla (RVLM) is dependent on viscerotopic representation of the kidney and the spleen in this region. Small (15 nl, 13 pmol) injections of the potent tau-aminobutyric acid agonist muscimol were used to map the RVLM of anesthetized rats, searching for areas that selectively provided tonic excitation of renal or splenic nerves. Most of the muscimol microinjections produced depressor responses and inhibition of sympathetic nerve activity. Activity of renal nerves was inhibited significantly more than that of splenic nerves, but we found no evidence for topographical organization of RVLM influences on tonic activity of these two nerves. However, this investigation did yield an important new observation, since approximately 10% of the injections caused pressor responses and increases in sympathetic discharge. The unexpected increases must have been caused by blockade of small groups of tonically active sympathoinhibitory neurons located throughout the RVLM. This disinhibition was not evoked from any specific region of the RVLM. In conclusion, the RVLM neurons and putative interneurons that tonically control the discharge of postganglionic renal and splenic neurons appear to be distributed homogeneously throughout this area. Neither excitatory nor inhibitory elements were organized topographically to specifically influence the renal or the splenic nerve. The neural organization responsible for the preferential effect on renal nerves may exist in the local microcircuitry within the RVLM and will be revealed only by an even more discrete analysis of these circuits. PMID- 1750527 TI - Experimental instrumentation and left ventricular pressure-strain relationship. AB - Pericardial pressure measurement with a balloon transducer requires opening and reapproximating the pericardium. If this instrumentation significantly compromises pericardial volume, the heart may be constrained, exaggerating the magnitude of pericardial pressure and thus altering the left ventricular end diastolic pressure-volume relationship. In open-chest dogs, we studied the effects of opening the pericardium, inserting a pericardial balloon transducer and myocardial sonomicrometer crystals, and reapproximating the pericardium on the left ventricular end-diastolic pressure-strain relationship (LVEDPSR). After a thoracotomy, sonomicrometer crystals were inserted through small holes (less than 3 mm) in the pericardium to measure LV segment length. A micromanometer with a reference lumen was used to measure LV pressure. LVEDPSRs were recorded in the following situations: 1) before the pericardium was opened (but after the crystals were inserted); 2) after the pericardium was opened, the heart was instrumented (4 pairs of crystals and 1 balloon), and the pericardium was reapproximated with interrupted sutures; and 3) after the pericardium was removed. For each dog, a cubic regression equation was fitted to the data obtained before opening the pericardium, and the 95% confidence intervals for the individual data points were determined. In each case, the LVEDPSR obtained after instrumentation was similar to the LVEDPSR described before opening the pericardium. Furthermore, data obtained after instrumentation were uniformly located within the confidence intervals of the LVEDPSR obtained before opening the pericardium and instrumenting the heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750528 TI - Glycolysis is predominant source of myocardial ATP production immediately after birth. AB - Glycolytic flux, as well as glucose, fatty acid, and lactate oxidation, was determined in isolated working hearts obtained from 1- and 7-day-old rabbits. One day-old rabbit hearts were perfused via the inferior cava against a constant aortic and pulmonary arterial afterload, whereas hearts from 7-day-old rabbits were perfused via the left atria against a constant aortic afterload. Hearts were perfused with buffer containing 100 microU/ml insulin and either 1) 11 mM [U 14C/2-3H]glucose, 0.4 mM palmitate, 2 mM lactate; 2) 11 mM glucose, 0.4 mM [1 14C]palmitate, 2 mM lactate; or 3) 11 mM glucose, 0.4 mM palmitate, 2 mM [U 14C]lactate. Glycolytic rates (measured as 3H2O production) were high in 1-day old hearts but decreased by 7 days (from 2,730 +/- 280 to 580 +/- 80 nmol.min-1.g dry wt-1). Rates of glucose oxidation (measured as 14CO2 production) were lower in both 1- and 7-day-old hearts (59 +/- 4.4 and 23 +/- 2 nmol.min-1.g dry wt-1). Palmitate oxidation rates were low in 1-day-old hearts but dramatically increased by 7 days (22.6 +/- 5.6 and 305 +/- 33 nmol oxidized.min-1.g dry wt-1, respectively). In contrast, lactate was readily oxidized by both 1- and 7-day-old hearts (169 +/- 14 and 456 +/- 52 nmol.min-1.g dry wt-1, respectively). In 1-day old hearts, 44% of steady-state ATP production from exogenous sources were derived from glycolysis, whereas 18, 13, and 25% were derived from glucose, palmitate, and lactate oxidation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750529 TI - Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels. AB - Pressure-induced myogenic responses and flow-induced vasodilatory responses have been documented in coronary resistance arterioles, but the interaction of these two mechanisms and the nature of the flow-mediated response are not well understood. Experiments were designed to quantitatively study the interaction of pressure- and flow-induced responses and to characterize the nature of the substance responsible for flow-mediated dilation in isolated coronary arterioles. Subepicardial arterioles (40-80 microns) were isolated from pigs and cannulated with two glass micropipettes and then pressurized via independent reservoir systems. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions thus generating a pressure gradient (delta P) without changing the mean intraluminal pressure (IP). IP was changed by moving both reservoirs in the same direction to alter myogenic tone in the absence of flow (delta P = 0). Flow-mediated dilation competed with myogenic constriction when flow and pressure were elevated. Also, flow potentiated myogenic dilation when IP was decreased. The magnitude of flow-induced dilation was greatest at an intermediate level of vascular tone (IP = 60 cmH2O) but was attenuated at higher and lower levels of tone. In the presence of flow (delta P = 4 cmH2O), pressure diameter relationships were shifted upward, and the magnitude of myogenic responsiveness was attenuated. Double-vessel bioassay studies indicated that a transferable substance was released from intact endothelium in response to flow. Flow-induced dilation was not affected by indomethacin but was abolished by NG monomethyl-L-arginine or by mechanical removal of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750530 TI - Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arterial tone. AB - In monkey and dog superficial temporal artery strips denuded of the endothelium, transmural electrical stimulation and nicotine produced a contraction that was abolished by phentolamine and potentiated by NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthesis inhibitor. The potentiation was reversed by L arginine but not by its D-enantiomer. The arteries treated with phentolamine and contracted with prostaglandin F2 alpha responded to the electrical stimulation and nicotine with relaxations that were abolished by tetrodotoxin and hexamethonium, respectively, and were markedly inhibited by L-NNA but not by D NNA, atropine, and timolol. The L-NNA-induced inhibition was reversed by L arginine. Nicotine increased the level of guanosine 3',5'-cyclic monophosphate in the monkey arteries; the increment was prevented by L-NNA. It is concluded that the monkey and dog temporal arterial tone appears to be reciprocally regulated by adrenergic vasoconstrictor and nonadrenergic noncholinergic vasodilator nerves. The neurogenic relaxation would be mediated by NO that is possibly released from the vasodilator nerve and transmits information to smooth muscle; therefore the nerve may be called "nitroxidergic." PMID- 1750531 TI - Abnormal Cai2+ handling is the primary cause of mechanical alternans: study in ferret ventricular muscles. AB - We tested the hypothesis that mechanical alternans of the heart is due to alternations in intracellular calcium (Cai2+) levels. Eight papillary muscles were isolated from the right ventricles of male ferrets and were chemically loaded with aequorin to record cytoplasmic Cai2+. To produce a steady-state mechanical alternans, the preparations were perfused with a physiological salt solution containing a low calcium concentration (0.25 mM), at 22 degrees C, and stimulated at 0.5-1.0 Hz in the presence of carbachol and propranolol. The aequorin signal (Cai2+) and isometric contraction were simultaneously recorded. In each muscle, the strong beats (beats with higher peak tension) were associated with larger Ca2+ transients than the weak beats. The relationships between peak Cai2+ and peak tension, both during strong and weak beats, were similarly modified by short-term frequency responses. On the other hand, the time courses of the isometric contractions and Ca2+ transients during strong beats and weak beats were superimposable. These data indicate that mechanical alternans is caused by an alternate change of Cai2+ available for activation of the myofilaments. Prolongation of the time for recycling Ca2+ by the sarcoplasmic reticulum, i.e., a depressed uptake function of the Ca2+ pump with concomitant slow transportation of Ca2+ from the uptake compartment to the release compartment in the sarcoplasmic reticulum, is suggested as a cause of the abnormal Cai2+ handling during mechanical alternans. PMID- 1750532 TI - Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate. AB - Acetoacetate, when present as the only fuel for respiration in rat hearts, causes an impairment in contractile function that is reversible with the addition of substrates that can contribute to anaplerosis. To determine the importance of pyruvate carboxylation via NADP(+)-dependent malic enzyme on metabolism and function in hearts oxidizing acetoacetate, isolated working rat hearts were perfused with [1-14C]pyruvate and acetoacetate. While the cardiac power output after 60 min of perfusion in hearts utilizing acetoacetate alone had fallen to 44% of the initial value, the addition of pyruvate resulted in a stable performance with no fall in the work output. When hydroxymalonate, an inhibitor of NADP(+)-dependent malic enzyme and malate dehydrogenase, was added to the two substrates, function at 60 min was similar to the value for hearts oxidizing acetoacetate alone. Measurements of the specific activities of malate, aspartate, and citrate confirm inhibition of both pyruvate carboxylation and malate oxidation. The findings are consistent with a mechanism in which the enrichment of malate by pyruvate improves function by increasing the production of reducing equivalents by the malate dehydrogenase and the isocitrate dehydrogenase reactions increase flux through the span of the tricarboxylic acid cycle from malate to 2-oxoglutarate. The present study demonstrates the physiological importance of anaplerotic pathways in maintaining contractile function in the heart. PMID- 1750533 TI - Blood volume changes in liver and spleen during cardiogenic shock in dogs. AB - Changes in vascular capacitance of the liver and spleen were studied in seven anesthetized dogs during cardiogenic shock induced by coronary microembolization. Left ventricular end-diastolic pressure increased from 2 +/- 2 to 28 +/- 4 mmHg (P less than 0.001), and mean aortic pressure decreased from 111 +/- 7 to 56 +/- 9 mmHg (P less than 0.001). Hepatic venous pressure increased from 1.8 +/- 0.6 to 5.0 +/- 1.0 mmHg (P less than 0.05). Portal venous pressure did not change. Blood volume changes were assessed from sonomicrometric measurements of organ diameters. Hepatic diameter increased after embolization, corresponding to an estimated 54 +/- 14 ml increase of hepatic blood volume (P less than 0.01). Splenic diameter gradually decreased during shock until an estimated 33 +/- 12 ml of blood had been released (P less than 0.05). Occlusion of hepatic venous outflow by a balloon catheter was used to cause ramp changes in hepatic volume and hepatic venous pressure so that a pressure-volume curve could be estimated. Analysis of the hepatic curves showed an increase in unstressed volume with no change in vascular compliance during shock. The blood volume increase could in part be attributed to increased outflow pressure, but active dilation of hepatic capacitance vessels probably contributed. Splenic curves were shifted downward, suggesting expulsion of blood by active contraction. PMID- 1750534 TI - External mechanical work during relaxation period does not affect myocardial oxygen consumption. AB - We assessed the effect of external mechanical work (EW) during the relaxation period (RP) on myocardial oxygen consumption (VO2) and clarified the energetic significance of the potential energy (PE) portion of the pressure-volume area (PVA) in the cross-circulated dog left ventricle. We changed the course of the relaxation segment of the pressure-volume (P-V) trajectory by increasing or decreasing EW within a given PVA without changing the end-diastolic volume (EDV) and the systolic segment of the P-V trajectory while measuring VO2. Thus the ventricle underwent ejection or filling during RP. Although the percent fraction of EW in PVA (%EW/PVA) was markedly increased from 32 +/- 12 (SD) to 93 +/- 3% in ejecting contractions (8 hearts) and from 0 to 93 +/- 5% in isovolumic contractions (3 hearts), these marked changes in %EW/PVA did not significantly affect VO2. Moreover, the VO2-PVA data during these procedures fell on the reference VO2-PVA relation line obtained by changing EDV and PVA of isovolumic contractions. We conclude that EW during RP at a constant PVA does not affect VO2 and part of PE can be converted into EW in an energetically equivalent manner. PMID- 1750535 TI - Endothelium-dependent vasodilation of canine coronary collateral vessels. AB - The objective of this study was to determine whether endothelium-mediated relaxation occurs in canine coronary collateral vessels. Responses to endothelium dependent vasodilators in coronary collateral vessels (250-350 microns) were compared with those obtained in normal native coronary arteries of similar size. Rings of small arteries and collateral vessels were suspended in baths, and tension was recorded. All rings were constricted with prostaglandin F2 alpha (3 microM) and subsequently exposed to cumulative concentrations of acetylcholine or bradykinin. In separate experiments, the procedure was repeated in the presence of 300 microM NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-mediated vasodilation. Endothelium-dependent relaxation was further studied in the presence of indomethacin, and endothelium-independent relaxation was examined with sodium nitroprusside. Acetylcholine and bradykinin relaxed both normal native and collateral rings. In preconstricted small arteries and collateral vessels the concentration at 50% of maximal response of acetylcholine was 85.5 +/ 19.5 and 61.0 +/- 14.0 microns, and bradykinin was 11.9 +/- 7.4 and 10.7 +/- 2.1 microns, respectively. L-NMMA attenuated the response to acetylcholine and bradykinin in both groups. The results indicate that endothelium is present and functional in canine coronary collateral vessels. Both small coronary arteries and collateral vessels are equally responsive to endothelium-dependent vasodilators and inhibition of endothelium-dependent relaxing factor. PMID- 1750536 TI - Coronary artery narrowing in rats: mechanical alterations of left and right myocardium. AB - To determine the effects of chronic coronary artery narrowing on myocardial contractile performance, nonocclusive constriction of the left coronary artery near its origin was surgically induced in rats and global cardiac hemodynamics, left and right myocardial mechanics, and the magnitude and distribution of tissue damage and interstitial fibrosis in the left ventricular wall were analyzed 1 mo later. Reductions in coronary artery luminal diameter of 55% resulted in left ventricular failure as characterized by decreases in systemic arterial pressures, systolic ventricular pressure, rise and decay in first derivative of left ventricular pressure (+/- dP/dt), and an increase in left ventricular end diastolic pressure. Right side dysfunction was also present as documented by an elevation in right ventricular end-diastolic pressure and a reduction in -dP/dt. In vitro measurements of papillary muscle mechanics revealed a biventricular reduction in isometric developed tension and peak rates of tension rise and decay. Moreover, the kinetic parameters of isometric contraction duration, time to peak tension and time to one-half relaxation, were significantly shorter in left muscles from coronary artery-narrowed animals. Isotonically, peak muscle shortening was reduced in the left muscle, whereas time to peak shortening was prolonged in the right myocardium. In addition, the velocities of muscle shortening and relengthening were decreased in both ventricles. Foci of replacement fibrosis and diffuse interstitial fibrosis were found in the epimyocardium, midmyocardium, and endomyocardium, demonstrating that a significant amount of myocyte loss occurred throughout the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750537 TI - Role of sinoaortic afferents in modulating BP and pulse-interval spectral characteristics in unanesthetized cats. AB - Sinoaortic denervation (SAD) is accompanied by an increase in blood pressure (BP) and a reduction in pulse-interval (PI) variance. Little is known, however, about the effect of SAD on the complex BP and PI variability pattern, which is identified by spectral analysis. In nine unanesthetized cats in which intra arterial BP was monitored before and 7-10 days after SAD, spectral powers (estimated by fast Fourier transform) were calculated for the low frequency (LF, 0.025-0.07 Hz), midfrequency (MF, 0.07-0.14 Hz), and high frequency (HF, 0.14 0.60 Hz) band. The very low frequency (VLF) BP and PI components (VLF less than 0.025 Hz) were also estimated. SAD increased systolic BP variance and decreased PI variance. The reduction of PI variance was paralleled by significant and marked reductions in all PI powers including the VLF components. In contrast, the increase in systolic BP variance was accompanied by a marked increase in LF power, a decrease in MF power, and no change in HF power. The VLF BP components increased after SAD for frequencies between 0.025 and 0.0012 Hz, whereas a sudden marked reduction was observed below 0.0012 Hz. Similar results were obtained for diastolic BP powers. Thus the reduction in PI variance induced by SAD is paralleled by a reduction in all PI fluctuations identified by spectral analysis. This is not the case for the SAD-related increase in BP variance, which is accompanied by an increase, no change, or even a reduction in the different BP spectral components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750538 TI - Regional circulatory contributions to increased systemic vascular conductance of pregnancy. AB - In pregnancy, maternal systemic vascular conductance increases, a new vascular circuit grows, and the maternal systemic circulation develops a diminished pressor response to angiotensin II (ANG II). However, the quantitative contributions of the latter two circulatory changes to the increased systemic vascular conductance of pregnancy have not been explored. In this experiment, we examined regional circulatory contributions to the increased systemic vascular conductance in conscious, late-gestation guinea pigs. Systemic arterial pressure, cardiac output (dye dilution), and regional blood flows (radiolabeled microspheres) were measured during baseline conditions and progressive ANG II infusion. Systemic and regional conductances were calculated from arterial pressure and cardiac output or regional blood flows. In pregnancy, maternal systemic vascular conductance increased from 3.2 to 5.0 ml.min-1.mmHg-1 (P less than 0.001); increased nonuteroplacental conductance contributed 71% to the increase in whole body conductance. Pregnancy tended to decrease the nonuteroplacental conductance response (P = 0.072), but did not change the uteroplacental conductance response (P greater than or equal to 0.29), to ANG II. The increased uteroplacental blood flow of pregnancy was preserved during ANG II induced vasoconstriction. We conclude that maternal systemic vascular conductance increased primarily because nonuteroplacental vascular conductance increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750539 TI - Protein kinase C and phospholipase C in adenosine receptor-mediated relaxation in coronary artery. AB - The effect of adenosine, 2-chloroadenosine (CAD), and 5'-(N-ethylcarboxamido) adenosine (NECA) on the contraction produced by phorbol 12,13-dibutyrate (PDB) was investigated in porcine coronary artery in vitro to determine whether adenosine receptor-mediated relaxation was linked to protein kinase C. Also, the coronary relaxation produced by adenosine and NECA in KCl-contracted coronary rings was investigated before and after treatment with the phospholipase C inhibitor neomycin to examine a possible link between phospholipase C and adenosine receptor-mediated relaxation. Ring segments of coronary artery were suspended in organ baths for measurement of isometric force. PDB (10 nM-1 microM) caused concentration-dependent contraction, and this response was significantly attenuated by pretreatment with the protein kinase C inhibitor staurosporine (200 nM) but not 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (10 microM). Treatment of rings with either adenosine, CAD, or NECA (100 microM) significantly attenuated the PDB-induced contraction, whereas treatment with either sodium nitroprusside (SNP; 1 microM) or isoproterenol (Isop; 1 microM) did not affect the contraction produced by PDB. The attenuation of the PDB-induced contraction by adenosine and its analogues was blocked by prior treatment of the coronary rings with 8-phenyltheophylline (10 microM). In a separate series of experiments, pretreatment of rings with the phospholipase C inhibitor neomycin (1 mM) resulted in a significant attenuation of the relaxing response to both adenosine and NECA while having no significant effect on the relaxation-response to SNP or Isop. These results provide indirect evidence that adenosine receptor-mediated relaxation in porcine coronary artery may be linked to modulation of protein kinase C and phospholipase C. PMID- 1750540 TI - Myocardial mechanics predict hemodynamic performance during normal function and alcohol-induced dysfunction in rats. AB - To determine whether mechanical evaluation of muscle tissue removed from the myocardium can be employed as a direct indicator of cardiac contractile performance in situ, isometric and isotonic parameters of muscle mechanics in vitro were correlated with in vivo global functional characteristics of the same heart. Twelve-month-old animals maintained on standard food and water were employed as representative of normal cardiac function. Animals of identical age with left ventricular (LV) dysfunction induced by oral alcohol (30%) ingestion from 4 to 12 mo were utilized to represent depressed cardiac performance. Accordingly, 24 h after the establishment of the hemodynamic profile for a control or experimental heart, the LV posterior papillary muscle was removed from the same heart and examined isometrically and isotonically. Least squares regression analysis was employed to establish a correlation coefficient and P values between various in vitro and in vivo parameters. Hemodynamic measurements were performed under chloral hydrate anesthesia and LV pump performance was evaluated with respect to aortic and ventricular pressures and the rates of rise and decay of the LV pressure trace. Papillary muscles were evaluated with respect to timing parameters of the isometric and isotonic twitch, the first derivative of isometric tension development, and the speed of muscle shortening at increasing physiologic loads. LV peak rate of pressure rise and decay were then correlated with the various isometric and isotonic properties. Myocardial mechanics and hemodynamics revealed depressed function in the papillary muscles and hearts from alcoholic rats. Moreover, significant correlations were found between the LV rate of pressure change (peak +dP/dt and -dP/dt) and both isometric and isotonic twitch measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750541 TI - Responses of atrium and ventricle to sustained sympathetic nerve stimulation. AB - To determine whether chronotropic and atrial inotropic responses to sympathetic nerve stimulation are maintained longer than ventricular inotropic response, the present study was performed with control and acute reserpinized dogs. We stimulated the right stellate ganglion of both groups supramaximally for 60 min and compared right atrial responses (chronotropism and inotropism) with left ventricular (LV) dP/dtmax. In the control group, heart rate (HR) immediately increased and was only slightly attenuated with 60 min of stimulation, and right atrial (RA) inotropic response was less attenuated than was LV response (7% in HR, 33% in RA dP/dtmax, 50% in LV dP/dtmax, P less than 0.01, from the peak value of each response). RA and LV norepinephrine (NE) content was decreased by the stimulation but remained higher than the LV control value. In the reserpinized group, NE content in the RA was low before the stimulation and was further decreased by the stimulation. In this group, HR response was attenuated (27% in HR, P less than 0.01) as was LV dP/dtmax, and the difference in contractile responsiveness between atrium and ventricle disappeared (58% in RA dP/dtmax vs. 61% in LV dP/dtmax, NS). The results indicate that the chronotropic response was only slightly attenuated and that the atrial contractile response was attenuated less than the ventricular response, with sustained sympathetic nerve stimulation in the normal heart. This can be ascribed to the much higher NE content in the RA than that in the LV. PMID- 1750542 TI - Immunoglobulin and renal abnormalities in Dahl genetically hypertensive rat. AB - The Dahl salt-sensitive rat (DS) is a model of genetically determined arterial hypertension exacerbated by dietary salt. We report two additional abnormalities of DS rats, which are both genetically determined and enhanced by salt: 1) immunoglobulin disorders and 2) renal dysfunctions. These abnormalities precede and are not the result of the arterial hypertension. In young, prehypertensive DS rats the plasma and tissue concentrations of immunoglobulin (Ig) G, but not of IgM or IgA, are decreased compared with those of the salt-resistant strain (DR). A high-salt diet (8.0% NaCl) decreases the plasma and tissue IgG levels of DS but not of DR rats. Reduction of IgG in the DS strain results from both decreased synthesis and increased urinary excretion. Renal dysfunction in young, prehypertensive DS animals is manifested by increased excretion of high molecular weight proteins, including albumin, IgG, IgA, and IgM. The high-salt diet increases the urinary excretion of these proteins within 1-2 days, and the effect is much greater in DS compared with DR rats. The urinary excretion of IgG is selectively increased relative to immunoglobulin light chains, IgA and IgM in DS compared with DR animals. The present studies provide new markers characteristic of the DS phenotype and pose the issue of possible genetic or functional interrelationships among the salt-sensitive hypertension, immunoglobulin disorders, and renal dysfunctions. PMID- 1750543 TI - Carotid baroreceptor control of right atrial mechanics in dogs. AB - To investigate the influence of the carotid arterial baroreceptors on right atrial mechanics, the carotid sinus region was isolated surgically in eight dogs prepared acutely under pentobarbital. Right atrial pressure and conductance volume were measured with a strain-gauge tip catheter and a conductance catheter, respectively. Reduction of carotid sinus pressure from 225 to 50 mmHg elicited significant increases in the a wave in right atrial pressure, in atrial stroke volume, in atrial stroke work (2.5-fold), and in atrial stroke power (4-fold). Mean central venous pressure and atrial volume at the onset of each beat did not change. These responses were unchanged after bilateral cervical vagotomy. Head-up tilt was applied at carotid sinus pressures less than or equal to 150 mmHg in four dogs to oppose any contribution of decreased systemic venous capacity to the responses through increased atrial filling. Tilt did not change atrial stroke work or atrial filling during late ventricular systole before vagotomy but inhibited these variables significantly after vagotomy. The slope of the relationship between right atrial stroke work and atrial volume at the onset of contraction increased significantly with reduction of carotid sinus pressure. This response was unaffected by either vagotomy or tilt. Carotid arterial hypotension appears to augment right atrial stroke work and stroke volume through an increase in atrial contractility. A decrease in venous capacity may contribute to this response especially after vagotomy. PMID- 1750544 TI - Cigarette smoke extract attenuates endothelium-dependent arteriolar dilatation in vivo. AB - The purpose of this study was to examine the effects of cigarette smoke extract on endothelium-dependent and endothelium-independent dilatation of arterioles in vivo. Using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with acetylcholine and nitroglycerin, before and after treatment with cigarette smoke extract. Under control conditions, acetylcholine and nitroglycerin produced dose related dilatation of cheek pouch arterioles. Superfusion of cigarette smoke extract (1.0%) did not alter baseline diameter of arterioles or vasodilatation in response to nitroglycerin but impaired dilatation of arterioles in response to acetylcholine. Next, we examined the possibility that impaired dilatation of cheek pouch arterioles in response to acetylcholine after exposure to cigarette smoke extract may be related to the release of substances produced via the cyclooxygenase pathway. In indomethacin-pretreated hamsters, acetylcholine produced similar vasodilatation before and after exposure to cigarette smoke extract. Thus these findings suggest that cigarette smoke extract impairs endothelium-dependent responses of cheek pouch arterioles. The mechanism of impaired responses of cheek pouch arterioles after exposure to cigarette smoke extract appears to be related to the release of substances produced via the cyclooxygenase pathway. PMID- 1750545 TI - Relationships between lymphatic pump flow and total lymph flow in the small intestine. AB - Response of collecting lymphatics to acute elevations in lymph formation was studied in vivo. Mesentery of 33 rats was prepared for intravital microscopic study, and indexes of lymph propulsion (contraction frequency, stroke volume, and ejection fraction) were monitored. In 14 rats, total lymph flow was measured by cannulating the main intestinal lymph trunk. After a control period, lymph flow was increased by hemodilution with isotonic saline. Right atrial pressure did not significantly increase during the hemodilution period. Total lymph flow increased to approximately 25 times control. Lymph propulsion (the product of stroke volume and contraction frequency) decreased in five lymphangions (group I). In 22 lymphangions, lymph propulsion increased one to five times control (group II). The remaining six lymphangions increased lymph propulsion by greater than five times control (group III). Group I possessed the largest end-diastolic diameter, highest baseline contraction frequency, and did not dilate as lymphatic filling increased. Group III possessed the smallest initial end-diastolic diameter and lowest baseline contraction frequency, and end-diastolic diameter doubled as lymphatic filling increased. The characteristics of group II were between those of groups I and III. Total lymph flow and lymph propulsion by group III lymphangions tended to agree when lymph flow was less than five times control. In more edematous conditions, total lymph flow exceeded lymphatic pump flow. The characteristics of group II were between those of groups I and III. Analysis of the location of various sized lymphangions within the lymphatic network indicated that the smaller group III lymphangions were located nearer the intestinal wall, and the larger group I lymphangions were nearer the outflow from the mesentery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750546 TI - Synergistic nonuniform shortening of atrial refractory period induced by autonomic stimulation. AB - We investigated the nonuniform effects of autonomic nerve stimulation of the effective refractory period (ERP) of the right atrium in the anesthetized dog. Stimulation of the discrete intracardiac sympathetic nerves to the sinoatrial (SA) nodal region uniformly shortened ERPs at three sites in the right atrium after administration of atropine. Right ansa subclavia (RS) stimulation similarly shortened ERPs in the absence of atropine. Stimulation of the discrete intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) shortened ERPs of the right atrium in a nonuniform manner. Simultaneous RS and SAP stimulation additively shortened ERPs at each site and decreased sinus rate much more than SAP stimulation alone. Shortening of ERP induced by SAP stimulation was greater than that induced by RS stimulation at similar absolute changes in heart rate. These results suggest that simultaneous activation of sympathetic and parasympathetic nerves nonuniformly shortens the ERP in the right atrium as the algebraic sum of the individual responses to each stimulation. However, parasympathetics exert the principal neural control over atrial ERP. PMID- 1750547 TI - Regulation of glycolytic flux by coronary flow in guinea pig heart. Role of vascular endothelial cell glycocalyx. AB - Hemodynamic forces continuously act on endothelial cell lining of blood vessels. Blood flow, perfusing pressure, and shear stress are known to induce the release of bioactive substances from the endothelium. Furthermore, coronary flow (CF) is a well-known stimulant of myocardial contraction. Our concern was whether other Ca(2+)-dependent responses like glycolytic flux (Gf) were also CF dependent. For this purpose, isolated guinea pig hearts were perfused with a medium containing 5 mM 3-[3H]glucose, and the 3H2O released during perfusion was measured as an index of Gf. Changes in CF within the 3- to 25-ml/min range resulted in linear increase of Gf. This stimulatory effect of CF was also observed in K(+)-arrested hearts. In addition, increasing shear stress on addition of dextran to the perfusing solution (5% and 10% wt/vol), while keeping CF constant, also stimulated Gf. We hypothesized that endothelial cell membrane glycocalyx may act as sensor to this stimuli. Thus one would expect that substances acting on these structures (enzymes heparinase, hyaluronidase, or chondroitinase or the lectin concanavalin A) when added to the perfusate might inhibit the CF-induced Gf. The results showed that concanavalin A and heparinase inhibited the Gf-CF-induced response, whereas chondroitinase and hyaluronidase had no effect. These findings suggest that there may be a selective effect of these agents affecting the Gf response to CF. Our data suggest that CF stimulates Gf through shearing forces acting on specific endothelial glycocalyx component(s). Therefore, deformation of these components could result in the transduction of physical signals into release of chemical messengers that act on the biochemical machinery of underlining parenchymal cells. PMID- 1750548 TI - Effect of an arginine analogue on acetylcholine-induced coronary microvascular dilatation in dogs. AB - The purpose of this study was to elucidate the contribution of endothelium derived relaxing factor (EDRF) derived from arginine to acetylcholine (ACh) induced coronary arteriolar vasodilatation in vivo. Experiments were performed in 62 open-chest anesthetized dogs. Internal diameters of small arterioles (less than 120 microns) and large arterioles (greater than 120 microns) were measured using an intravital microscope and stroboscopic epiillumination synchronized to the cardiac cycle. Topically administered NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) M) constricted small arterioles (-10.7 +/- 3.1% from control diameter, P less than 0.05), but L-NMMA did not produce vasoconstriction in large arterioles. ACh, in the absence of L-NMMA, caused a dose-dependent vasodilatation in both small and large arterioles. In large arterioles, L-NMMA completely abolished the ACh-induced vasodilatation (10(-5) M topical ACh: from 13.3 +/- 3.0 to -2.0 +/- 1.5%, P less than 0.05; 10(-4) M ACh: from 20.9 +/- 3.9 to -3.0 +/- 1.9%, P less than 0.01). In small arterioles, L-NMMA only partially inhibited the vasodilatation (10(-5) M ACh: from 35.4 +/- 4.0 to 19.0 +/- 2.7%, P less than 0.05; 10(-4) M ACh: from 42.5 +/- 4.8 to 22.6 +/- 3.1%, P less than 0.05). L Arginine (10(-3) M topically) reversed L-NMMA inhibition of ACh-induced vasodilatation. Persistent dilatation of small arterioles also occurred when NG nitro-L-arginine rather than L-NMMA was administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750549 TI - Arteriovenous oxygen diffusion shunt is negligible in resting and working gracilis muscles. AB - Distribution of O2 within and among arterioles and venules was determined in dog and rat gracilis muscles with a cryospectrophotometric method. Saturation in 40 microns arterioles was not demonstrably different from saturation in the aorta even when flow was abnormally low. Arterioles greater than 40 microns ran parallel to venules. Measurements and a mathematical model indicate that diffusive shunting is negligible for typical separation distances between arterioles and venules. Most separation distances were greater than 30 microns. In some venule segments less than 15 microns from an arteriole, saturation within 10 microns of the wall facing the arteriole was higher than at other locations within the venule. However, saturation in the population of venules did not increase with venule diameter, and mean venular saturation was not different from saturation in effluent blood. We make the following conclusions: 1) a small arteriovenous diffusive O2 flux exists in postural muscles; 2) contribution of this flux to O2 mass balance is negligible; 3) O2 diffusivity of the arteriolar wall and surrounding tissue in vivo cannot be much higher than O2 diffusivity determined in vitro; and 4) effluent PO2 closely approximates mean end-capillary PO2. PMID- 1750550 TI - Pulse-chase study on lipoprotein lipase in perfused guinea pig heart. AB - Lipoprotein lipase (LPL) in guinea pig hearts was labeled by perfusion for 15 min with [35S] methionine, followed by chase perfusion with unlabeled medium for less than or equal to 90 min. Suitable conditions for pulse and chase and for immunoprecipitation of LPL were worked out. Differences in labeling between individual hearts were found to be substantial. A technique to take serial biopsies (approximately 20 mg) from the heart ventricle was therefore worked out and validated. Regional differences of LPL labeling within the ventricle were small. There was no evidence for enhanced release of LPL caused by biopsy. When heparin was present throughout the chase, labeled LPL began to appear in the medium after 30 min. Thus LPL can move rapidly from synthesis in parenchymal cells to the endothelial surface and into the medium. After 90 min chase with heparin, approximately equal amounts of LPL (approximately 32%) had been released to the medium, remained in the heart, or had been degraded, respectively. In contrast, no detectable amount of labeled LPL appeared in the medium during 90 min chase without heparin, and a heparin flush at this time brought out only approximately 9% of the pulse-labeled LPL. PMID- 1750551 TI - Role of xanthine dehydrogenase and oxidase in focal cerebral ischemic injury to rat. AB - The role of xanthine dehydrogenase and oxidase as a source of free radicals contributing to focal cerebral ischemic injury was evaluated in Long-Evans rats after the middle cerebral artery was permanently occluded and both carotid arteries were clamped for 90 min. The fraction of xanthine dehydrogenase present as the free radical producing oxidase increased slightly from 22% in control cortex to 30% in the ischemic right cortex during the first 3 h of reperfusion and then remained relatively unchanged over the next 24 h. This increase may in part be due to entrapped plasma, which contained 4.5 +/- 0.8 nmol.min-1.ml-1 xanthine oxidase entirely in the free radical-producing form. Infarct volume was unaffected by pretreatment with 50 mg allopurinol/kg per day over 3 days before surgery but was decreased by 8% with 100 mg/kg and 24% with 150 mg/kg of allopurinol (P less than 0.05). However, inhibition of xanthine oxidase by dietary depletion of the essential molybdenum cofactor increased infarct volume by 19%, suggesting that protection by allopurinol at higher dosages was independent of xanthine oxidase inhibition. Neither xanthine oxidase present in rat brain nor circulating in plasma appears to be the primary source of oxygen radicals that contributes to infarction in focal cerebral ischemia. PMID- 1750552 TI - Measurement of regional glucose metabolic rates in reperfused myocardium. AB - Regional myocardial glucose utilization was measured with [18F]fluorodeoxyglucose (FDG) and positron emission tomography in normal and postischemic tissue after 3 h of intracoronary balloon occlusion in closed-chest chronically instrumented anesthetized dogs. Estimates of glucose metabolic rates were made using the Sokoloff model, assuming the lumped constant to be unchanged in reperfused tissue. Myocardial sectors were classified as normal, reversibly injured, or infarct containing based on occlusion blood flow images and postmortem histology. Occlusion flow, measured by microspheres, was reduced by 38% in reversibly injured and 74% in infarct-containing sectors, recovering to 91 and 66%, respectively, 1 h postreperfusion. One month postreperfusion, flow was normal in reversibly injured sectors but remained depressed at 60% in infarct-containing sectors. Glucose utilization at baseline was homogeneous, averaging 0.8 mumol.g 1.min-1. After 3 h of reperfusion following occlusion of the left anterior descending coronary artery, regional glucose metabolic rate was increased 60% relative to baseline in normal myocardium but not in postischemic sectors, leading to an enhancement of FDG uptake in normal relative to postischemic myocardium. At 24 h postreperfusion, the glucose metabolic rate decreased in normal remote tissue to 46% of baseline levels, probably reflecting increased plasma free fatty acid levels, but was not significantly altered in reversibly injured myocardium, leading to enhanced FDG uptake in reversibly injured relative to normal myocardium. Subsequently, glucose metabolism in normal and postischemic sectors was not significantly different. Prolonged relative enhancement of glucose metabolic rate in postischemic tissue was found when the glucose metabolic rate in normal myocardium was low. Myocardial glucose utilization correlated with hg, the rate constant for FDG phosphorylation under all conditions (r = 0.88). PMID- 1750553 TI - Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade. AB - Ischemically sensitive abdominal visceral afferents are known to reflexly stimulate the cardiovascular system. These nerve endings respond to severe hypoxia as well as to exogenously administered bradykinin and prostaglandins such as PGI2, PGE, and PGF2 alpha. We have shown previously that these prostaglandins can sensitize some previously unresponsive afferents to respond to ischemia. To determine if endogenously produced prostaglandins contribute to the observed increase in activity during ischemia, we recorded activity of 6 A delta- and 23 C fiber sympathetic afferents in anesthetized cats during 5 min of ischemia before and 15-30 min after intravenous administration of either indomethacin (5 mg/kg) or aspirin (50 mg/kg). Before cyclooxygenase inhibition, we noted repeatable increases of 1.44 +/- 0.22 and 1.44 +/- 0.36 impulses/s in the A delta- and C fibers, respectively, in response to ischemia. After indomethacin or aspirin, these increases were significantly reduced (P less than 0.05) in both thinly myelinated and unmyelinated afferents (0.69 +/- 0.36 and 0.46 +/- 0.21 impulses/s, respectively). In a second protocol, we observed that the activity of six A delta- and seven C-fibers was significantly reduced by aspirin or indomethacin when a single period of ischemia preceded cyclooxygenase blockade. These data, in conjunction with our previous observations, indicate that prostaglandins significantly contribute to the increased afferent discharge activity associated with ischemia of the abdominal visceral region. PMID- 1750554 TI - Independent dual perfusion of left and right coronary arteries in isolated rat hearts. AB - A novel dual lumen aortic cannula was designed and constructed to permit independent perfusion of left and right coronary beds in isolated rat hearts without necessitating the cannulation of individual arteries. Stability of the dual-perfusion preparation was shown to be similar to that of the conventional Langendorff preparation, in terms of coronary flow, heart rate, and high-energy phosphate content. The independence of left and right perfusion beds was confirmed by unilateral infusion of disulfine blue dye and spectrophotometric detection of the dye in ventricular homogenates. Transient cessation of flow to the left coronary bed resulted in severe ventricular arrhythmias upon reperfusion, as in conventional models of regional ischemia and reperfusion. The dual-perfusion model is technically undemanding, reproducible, inexpensive, and can be used in several species. It enables studies with 1) regional low flow ischemia, 2) regional zero-flow ischemia without coronary ligation (with attendant damage to vasculature), 3) selective application of drugs or interventions to the ischemic-reperfused zone, and 4) selective application of components of ischemia and reperfusion to a site anatomically relevant to ischemic heart disease. PMID- 1750555 TI - 1H-nuclear magnetic resonance deoxymyoglobin signal as indicator of intracellular oxygenation in myocardium. AB - We report in this study that the intracellular oxygenation state is measurable with the 1H nuclear magnetic resonance signal of the proximal histidine N delta H proton of deoxymyoglobin. The signal appears in a clear spectral region of the 1H spectrum and is sensitive to various hypoxic and ischemic conditions. In perfused heart, the deoxymyoglobin's response to tissue oxygenation precedes the one reflected in the 31P phosphocreatine or ATP signals, suggesting that oxidative energy metabolism is still sufficient even when the myoglobin is partially saturated with oxygen. Our method offers then a unique way to observe tissue oxygenation and its interaction in localized tissue region in vivo. PMID- 1750556 TI - Lipid-soluble cardiodepressant factor vs. water-soluble myocardial depressant factor-like substances in shock. PMID- 1750557 TI - Comparative insights into the mechanisms of renal organic anion and cation secretion. AB - Comparative models have played a major role in defining the mechanisms that enable vertebrate proximal tubules to transport organic anions and cations from the peritubular interstitium to the urine. The unique advantages of these models and their contributions to our understanding of organic anion and cation transport mechanisms are summarized here. Recent studies of the organic anion transport system suggest that transport is coupled to metabolic energy via indirect coupling to the sodium gradient. Organic anions enter the cell across the basolateral membrane in exchange for alpha-ketoglutarate (alpha-KG), and the alpha-KG is returned to the interior via Na-alpha-KG cotransport. Indirect coupling to Na has been demonstrated in both isolated membranes and intact renal epithelial cells of species ranging from marine crustaceans to mammals. This mechanism was shown to drive not only cellular accumulation but also secretory transepithelial fluxes of organic anions. Luminal exit of secreted organic anions appears to be carrier mediated but is, at present, poorly understood, with mediated potential-driven efflux and anion exchange-driven efflux implicated in some species. As for organic anions, the renal clearance of some organic cations approaches the renal plasma flow. Although there is considerable variation in the handling of specific substrates between species, the basic properties of organic cation transport include carrier-mediated potential-driven uptake at the basolateral membrane, intracellular sequestration that reduces the free concentration of the cation, and luminal exit by organic cation-proton exchange. Reabsorptive transport is also observed for some organic cations, but its mechanisms and driving forces are not well understood. PMID- 1750558 TI - Freeze-thaw injury in erythrocytes of the freeze-tolerant wood frog, Rana sylvatica. AB - Erythrocytes from the freeze-tolerant wood frog (Rana sylvatica) were subjected to in vitro tests of freeze tolerance, cryoprotection, and osmotic fragility. The responses of cells from frogs acclimated to 4 or 15 degrees C were similar. Erythrocytes that were frozen in saline hemolyzed at -4 degrees C or lower. The addition of high concentrations (150 and 1,500 mM) of glucose or glycerol, cryoprotectants produced naturally by freeze-tolerant frogs, significantly reduced cell injury at -8 degrees C, but concentrations of 1.5 or 15 mM were ineffective. Hemolysis was reduced by 94% with 1,500 mM glycerol and by 84% with 1,500 mM glucose; thus glycerol was the more effective cryoprotectant. Mean fragility values for frog erythrocytes incubated in hypertonic and hypotonic saline were 1,938 and 49 mosM, respectively. Survival in freeze tolerance and cryoprotection experiments was comparable for erythrocytes from frogs and humans, suggesting that these cells may respond similarly to freezing-related stresses. However, the breadth of osmotic tolerance, standardized for differences in isotonicity, was greater for frog erythrocytes than for human erythrocytes. Our data suggest that erythrocytes from R. sylvatica are adequately protected by glucose under natural conditions of freezing and thawing. PMID- 1750559 TI - Glucose increases rat plasma norepinephrine levels by direct action on the brain. AB - The hypothesis that glucose can selectively activate the sympathetic nervous system (SNS) by direct action on the brain was tested using plasma norepinephrine (NE) and epinephrine (Epi) responses to intracarotid and intravenous glucose injections as indexes of SNS and adrenal medullary responses, respectively. Intracarotid glucose bolus injections (0.1 g/kg) transiently raised plasma glucose (22%) and insulin (98%) levels at 2 min and increased plasma NE, but not Epi, levels from 2 to 60 min. Areas under the NE curve were 700% higher than equiosmolar doses of mannitol. An intravenous glucose bolus (1 g/kg) gave quantitatively similar but delayed (30 min) NE responses to the 0.1 g/kg intracarotid dose but raised plasma glucose 500% and insulin 1,700% above baseline at 2 min postinjection. Slow intracarotid glucose infusions for 60 min at 4 mg.kg-1.min-1 raised plasma NE levels from 30 to 60 min with 250% higher areas under the NE curve than the intracarotid and intravenous bolus doses but without a change in plasma glucose, insulin, or Epi levels. Infusions at 6 mg.kg 1.min-1 transiently raised plasma NE levels at 30 min without altering glucose, insulin, or Epi levels. These results suggest that glucose alone can produce a selective, delayed SNS activation by a direct action on the brain. PMID- 1750560 TI - Role of gram-negative and gram-positive gastrointestinal flora in temperature regulation of mice. AB - An earlier study showed that the presence of gut flora elevates body temperature of mice and rats. In these experiments, we questioned whether the signal coming from the gut was endotoxin from gram-negative (Gm-) bacteria or some signal derived from gram-positive (Gm+) microorganisms. To test the idea that endotoxin is responsible for the effects of flora, we compared the temperature of the endotoxin-resistant mouse (C3H/HeJ) with that of endotoxin-sensitive strains of mice (C3H/SnJ and C3H/HeN). Temperature of C3H/HeJ was not different from that of C3H/SnJ or C3H/HeN during the light period but was significantly lower during the later hours of the dark period. We speculated that, if endotoxin leaking across the gut wall were responsible for elevating temperature, then reduction of gut flora with nonabsorbable antibiotics would depress the temperature of the endotoxin-sensitive mice more than that of the endotoxin-resistant mice. Because antibiotics lowered the temperature of both strains of mice to the same extent, the signal coming from the gut is unlikely to be endotoxin. To test whether Gm+ flora can be responsible for elevating temperature, we inoculated one group of germfree mice with Gm+ organisms. Their mean temperature was significantly higher than that of mice that remained germfree. Cecectomy had no effect on temperature, indicating that the special properties of the germfree cecum were not involved in lowering the temperature of germfree mice. These data support the hypotheses that Gm+ organisms are a major source of the stimulatory effect of flora on normal body temperature and that the presence of Gm- organisms is unnecessary. PMID- 1750561 TI - Role of adrenal catecholamines during forced submergence in ducks. AB - Maximum underwater tolerance (UTmax) of chronically adrenalectomized ducks (ADX, 5.3 +/- 0.3 min) and chronically adrenal-denervated ducks (DNX, 7.2 +/- 0.2 min) was significantly lower than sham-operated controls (SH-ADX, 10 +/- 0.8 min; SH DNX, 12.2 +/- 0.5 min). After 4 min forced submergence, heart rates of ADX (62 +/ 16 beats/min) and DNX (31 +/- 2 beats/min) ducks were significantly higher than in their respective sham-operated controls (23 +/- 3 and 17 +/- 2 beats/min), although their blood pressure was significantly lower. Arterial partial pressure of O2, arterial O2 content, arterial pH, and lactate levels in DNX ducks (42 +/- 2 mmHg, 4.5 +/- 0.8 ml O2/100 ml blood, 7.233 +/- 0.016, 3.1 +/- 0.3 mM, respectively) were significantly lower than in SH-DNX ducks after 5 min forced submergence (53 +/- 1 mmHg, 6.8 +/- 0.4 ml O2/100 ml blood, 7.301 +/- 0.007, 4.8 +/- 0.4 mM, respectively). Venous infusion of catecholamines in ADX and DNX ducks during forced submergence significantly increased UTmax. It is suggested that adrenal catecholamines increase tolerance to underwater submersion by enhancing peripheral vasoconstriction, thus preserving the O2 stores for the heart and brain. Other adrenal products could also be involved. PMID- 1750562 TI - Intraruminal rehydration of ovine fetuses. AB - During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water. PMID- 1750563 TI - Regulation of food intake and body weight in rats by the synthetic heme analogue cobalt protoporphyrin. AB - Cobalt protoporphyrin (CoPP) in single subcutaneous doses produces prolonged weight loss in adult and aged male rats. The altered body weight level in treated animals is actively defended against starvation or overfeeding over prolonged time periods (greater than 50-100 days). The actions of CoPP on appetite and body weight regulation are biphasic, comprising an initial period of hypophagia, probably mediated centrally, until a particular body weight level is attained. Resumption of normal calorie intake follows, although lowered body weight levels are sustained, suggesting an additional action of the compound on peripheral substrate metabolism. Controlled decrements in body weight can be produced by repetitive low-dose CoPP treatment (e.g., 1 mumol/kg body wt weekly); low-dose regimens do not elicit altered hormonal homeostasis or aberrations in heme/cytochrome P-450 regulation that have been observed following larger doses (25-50 mumol/kg body wt) of the compound. CoPP may be a valuable probe with which to explore the role of heme-related molecules in the regulation of appetite and body weight. PMID- 1750564 TI - Intracerebroventricular administration of cobalt protoporphyrin elicits prolonged weight reduction in rats. AB - Intracerebroventricular administration of the synthetic heme analogue cobalt protoporphyrin (CoPP) results in a dose-dependent decrease in body weight in rats. Among several other metalloporphyrins tested, this effect was found to be specific to cobalt chelated in native or minimally modified protoporphyrin rings. Metabolic balance studies showed that the initial effect of intracerebroventricular treatment with CoPP (0.4 mumol/kg body wt) was a transient reduction in food intake. However, following resumption of normal food intake and growth rate, absolute body weights remained reduced for prolonged periods of time (200-300 days) in both male and female rats. Heme oxygenase activity was induced and cytochrome P-450 activities were reduced in both brain and hypothalamus following intracerebroventricular administration of CoPP. The proximate mechanism of action of this synthetic heme analogue is not known at present, but it appears to act in the central nervous system, probably in the vicinity of the hypothalamus, to reduce the body weight set point of treated animals. PMID- 1750565 TI - Elevations of plasma glucose do not support taste-to-postingestive consequence learning. AB - We examined whether elevations in plasma glucose are a sufficient postingestive consequence to support taste-to-postingestive consequence learning. Because real, but not sham, feeding supports taste-to-postingestive consequence learning, we recorded changes in plasma glucose during sham and real feeding. For the 1st 15 min of the meal, both sham and real feeding produced similar elevations in plasma glucose. Thereafter, real feeding produced sustained elevations in plasma glucose, whereas sham feeding did not. However, mimicking the plasma glucose profile of real feeding in the sham feeding rat by infusing glucose intravenously did not produce taste-to-postingestive consequence learning. Using radiolabeled sucrose, we determined that the rise in plasma glucose during sham feeding results from absorption of nutrient. We conclude that elevations in plasma glucose in isolation are not a sufficient consequence to support taste-to postingestive consequence learning. PMID- 1750566 TI - Heart rate variability as a measure of autonomic function during weight change in humans. AB - Changes in autonomic function were studied during experimentally induced weight changes in seven subjects. A spectral analysis of heart rate variability (HRV) was used to evaluate autonomic activity during weight change. With a 10% increase in body weight above the usual or starting weight, there was a decline in parasympathetic power accompanied by a rise in mean heart rate. Heart rate declined during weight reduction, but the power of HRV did not change significantly. Because heart rate power at the frequency of respiratory rate can be affected by respiratory rate, three additional subjects were tested at a constant respiratory rate. Weight increases in this group also led to a decline in the power of HRV at a frequency attributable to the parasympathetic nervous system. Such a parasympathetic effect of weight increase may be one mechanism for the arrhythmias and other cardiac alterations that accompany obesity. PMID- 1750567 TI - Low salt mimics effects of dark pulses on circadian pacemaker in cultured chick pineal cells. AB - Chick pineal cells in static culture display a persistent photosensitive circadian rhythm of melatonin production and release. Pulses of white light or darkness, in otherwise constant red light, induce phase shifts in subsequent cycles whose magnitude and direction depend on the phase at which the pulse is given. Such "phase-dependent phase shifts" are mediated by effects on the underlying pacemaker. We reported previously that inhibiting the Na-K-ATPase with ouabain or salt solutions lacking potassium evokes phase shifts with the same phase dependence as those induced by pulses of darkness. One of the consequences of inhibiting the sodium pump is cell swelling. To test the relevance of this effect, we exposed chick pineal cells to pulses of medium containing reduced concentrations of NaCl, which should cause cell swelling. These hypotonic solutions induced phase shifts in the melatonin rhythm with the same phase dependence as those caused by pulses of ouabain or darkness. The size of the phase shifts varied with degree of dilution, and phase shifting was prevented by replacement of NaCl. In view of previous results showing that hypertonic media mimicked the phase-shifting effects of light, these results suggest that cell swelling may mediate the darklike effects of ouabain on the circadian pacemaker in chick pineal cells. PMID- 1750568 TI - Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats. AB - Conscious rats treated with bolus endotoxin (ET; 4.0 mg/kg) increased plasma epinephrine (Epi) 48-fold (from 134 +/- 5 to 6,545 +/- 1,607 pg/ml) at 30 min, but by 6 h this elevation was less than 9-fold above control (1,174 +/- 166 pg/ml). In contrast, plasma norepinephrine (NE) elevation (6.5-fold above control) was maintained during the protocol. The present study was designed to test the hypothesis that the decreased Epi response following ET was due to 1) depletion of adrenal Epi content such that adrenomedullary stimulation would not release Epi, 2) decreased Epi release with direct stimulation, i.e., desensitization of release, or 3) decreased afferent signals generated by ET itself. In these experiments an initial low ET dose (0.5 mg/kg) was followed 3 h later by a second dose of either the same (0.5 mg/kg) or greater (4.0 mg/kg) magnitude. Plasma Epi was elevated following the initial (low) dose but not following the same second (0.5 mg/kg) dose, whereas the second higher dose (4.0 mg/kg) resulted in elevated plasma Epi. This response to high dose was 60% less than that observed with 4.0 mg/kg as an initial dose. Just before the second ET bolus, there was no depletion of adrenal Epi content (P greater than 0.05 saline vs. ET treated), and direct nerve stimulation demonstrated enhanced rather than attenuated Epi release from the adrenal medulla (P less than 0.05 saline vs. ET treated). These results suggest that the decline in Epi following the ET-induced elevation may be mediated by a decrease in the afferent signal that initiates Epi release. PMID- 1750569 TI - Development of passive permeability characteristics of rat placenta during the last third of gestation. AB - To investigate how the passive permeability of the rat placenta changes during the last third of gestation we measured the unidirectional maternofetal clearance (Kmf) of three polar nonelectrolytes. We found that Kmf (microliters.min-1.g placenta-1) for all three tracers increased between days 15 and 22 (term is 23 days). The increase was less for the largest tracer, [14C]inulin (3.5-fold increase from 0.5 +/- 0.1 to 1.6 +/- 0.1 microliters.min-1.g placenta-1), than for the smaller tracers, [14C]mannitol (7-fold increase from 1.6 +/- 0.1 to 10.9 +/- 0.4 microliters.min-1.g placenta-1) and 51Cr-labeled EDTA (9.5-fold increase from 0.8 +/- 0.04 to 7.6 +/- 0.7 microliters.min-1.g placenta-1). These data suggest that whilst the overall permeability of the rat placenta increases during this period of pregnancy, restriction to the diffusion of large (greater than or equal to 1.5 nm molecular radius) polar nonelectrolytes also increases. PMID- 1750570 TI - Compartmental analysis and glomerular filtration in chick embryos. AB - We have developed microtechniques that allow the determination of compartmental fluid distribution and glomerular filtration rate in chick embryos during three significant developmental periods: phase 1, the developmental period when the mesonephros alone is functioning; phase 2, periods of simultaneous meso/metanephric kidney function; and phase 3, the period during late development when the metanephros completely replaces the degenerated mesonephros. Water content of tissues is greater in younger embryos (89.4 +/- 0.2%, day 10) compared with older animals (78.3 +/- 0.5%, day 18). Although all major tissue components show an absolute increase in mass during this period, the embryo proper increases at five times the rate of the extraembryonic tissues. Glomerular filtration rate increases during development from 0.61 +/- 0.08 ml/h at day 10 to 2.31 +/- 0.11 ml/h at day 18. Glomerular filtration rate scales to body mass with an allometric exponent identical to adult birds only if total tissue mass (embryo + membranes) is considered. Our data suggest that significant errors in allometry will be encountered when scaling measurements are made on embryonic or fetal amniotes without taking into consideration the extraembryonic tissues. PMID- 1750571 TI - Effect of desipramine on norepinephrine metabolism in humans: interaction with aging. AB - To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake. PMID- 1750572 TI - Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats. AB - The basis for astrocytic swelling after the early period after portacaval anastomosis (PCA) is poorly defined. In other eukaryotic cells intracellular pH (pHi) and volume are determined, in part, by the same general mechanisms, yet how astrocytic pHi varies with enlargement of these cells after PCA is unknown. Therefore, direct measurements of pHi in astrocytes were made and compared with pericapillary astrocytic area as determined from electron micrographs in rats 5-8 days after PCA. Astrocytic area (n = 14 measurements for each group) was found to be significantly (P less than 0.0009) greater in PCA animals (n = 3) than in sham operated control animals. (n = 3). Double-barrel pH-sensitive microelectrodes were used to measure pHi in neocortical cells defined by electrophysiological criteria to be astrocytic. Astrocytes (n = 25) from PCA animals (n = 5) had a resting membrane potential of 72 +/- 5 mV (mean +/- SD) and an pHi of 7.11 +/- 0.11 while comparable cells (n = 12) from sham-operated controls (n = 2) had a membrane potential of 81 +/- 6 mV and an pHi of 7.00 +/- 0.10. Astrocytes from PCA animals were significantly more depolarized (P less than 0.001) and alkaline (P less than 0.009), at a time when they were also significantly larger than those from sham-operated controls. Astrocytes are known to become more alkaline when they are activated by brief depolarizing stimuli. However, this is the first demonstration that such an interrelationship can also exist for steady-state conditions of these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750573 TI - Role of angiotensin in ameliorating the renal actions of norepinephrine. AB - To determine the importance of the arterial pressure effects of angiotensin II (ANG II) on renal function during acute renal adrenergic stimulation, we examined the effects of a 2-h intrarenal arterial infusion of norepinephrine (NE) at 0.1 and 0.25 micrograms.kg-1.min-1 on renal function in five conscious dogs during 1) control conditions, 2) servo-control of renal arterial pressure (RAP) at control levels, and 3) chronic captopril administration. The low rate of NE infusion produced an approximately 20% decrease in glomerular filtration rate (GFR) and renal plasma flow (RPF) and an approximately 8-mmHg increase in RAP in association with an approximately 2.5-fold rise in plasma renin activity (PRA). The high rate of NE infusion produced greater increments in both PRA and RAP and an approximately 50% reduction in GFR and RPF. Neither servo-control of RAP nor captopril administration significantly affected the above renal responses to the low rate of NE infusion. In marked contrast, when increases in RAP (approximately 20 mmHg) were prevented at the high rate of NE infusion by servo-control of RAP, both the PRA and renal responses were enhanced. Furthermore, when RAP was reduced (approximately 25 mmHg) as a result of chronically blocking the renin-angiotensin system with captopril, the renal responses to the high rate of NE infusion were exaggerated even further; in four of five dogs, total renal ischemia occurred in response to NE. These results indicate that ANG II indirectly ameliorates the renal actions of renal adrenergic stimulation by increasing RAP. PMID- 1750574 TI - Increase in hepatic blood flow during early sepsis is due to increased portal blood flow. AB - Although hepatic blood flow increases significantly during early sepsis [as produced by cecal ligation and puncture (CLP)], it is not known whether this is due to the increase in portal or hepatic arterial blood flows. To study this, rats were subjected to CLP, after which they and sham-operated rats received either 3 or 6 ml normal saline/100 g body wt subcutaneously (i.e., all rats received crystalloid therapy). Blood flow in various organs was determined by using a radioactive microsphere technique at 5 and 20 h after CLP or sham operation. Portal blood flow was calculated as the sum of blood flows to the spleen, pancreas, gastrointestinal tract, and mesentery. Total hepatic blood flow was the sum of portal blood flow and hepatic arterial blood flow. A significant increase in portal blood flow and in total hepatic blood flow was observed at 5 h after CLP (i.e., early sepsis), and this was not altered by doubling the volume of crystalloid resuscitation after the induction of sepsis. In contrast, hepatic arterial blood flow during early sepsis was found to be similar to control; however, it was significantly reduced in late sepsis (i.e., 20 h after CLP). Cardiac output was significantly higher than the control in early sepsis. However, even in late sepsis, cardiac output and total hepatic blood flow were not significantly different from controls. These results indicate that the increased total hepatic blood flow during early hyperdynamic sepsis is solely due to the increased portal blood flow. PMID- 1750575 TI - Inhibitory renorenal reflexes: a role for renal prostaglandins in activation of renal sensory receptors. AB - In anesthetized rats, activation of renal sensory receptors with a mechanical stimulus (increased ureteral pressure) and a chemical stimulus (renal pelvic perfusion with 0.9 M NaCl) results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion, i.e., a contralateral inhibitory renorenal reflex. Because both interventions are known to increase renal prostaglandin (PG) synthesis, we examined whether renal PGs were involved in the renorenal reflex response to renal sensory receptor stimulation. In the first part, mechanical and chemical activation of renal sensory receptors was performed in the absence and presence of renal pelvic perfusion with indomethacin or meclofenamate (0.2 micrograms/min). Indomethacin inhibited the ipsilateral afferent renal nerve activity response to increased ureteral pressure (7 +/- 2 vs. 38 +/- 10%, P less than 0.01) and renal pelvic perfusion with 0.9 M NaCl (3 +/- 3 vs. 28 +/- 5%, P less than 0.01) and the contralateral diuretic and natriuretic responses in the absence of any renal hemodynamic changes. Similar effects were produced by meclofenamate. In the second part, mechanical and chemical activation of renal sensory receptors was performed in the presence of renal pelvic perfusion with vehicle, indomethacin, and indomethacin plus PGE2 (20 micrograms/min). Addition of PGE2 to the renal pelvic perfusate in indomethacin-treated kidneys restored the responses to mechanical and chemical activation of renal sensory receptors to levels not different from their pre-indomethacin control values. We conclude that PGs in the renal pelvic area are involved in inhibitory renorenal reflex responses to mechanical and chemical activation of renal sensory receptors. PMID- 1750576 TI - Inhibition of gluconeogenesis by extracellular ATP in isolated rat hepatocytes. AB - The aim of this study was to determine the effect of externally added ATP on gluconeogenesis by isolated hepatocytes from starved rats. High concentrations of extracellular ATP inhibited gluconeogenesis from lactate and pyruvate but not from glycerol or fructose. This inhibition was associated with an increase in intracellular adenosine contents. ADP, AMP, or adenosine but not guanosine 5'triphosphate, inosine 5' triphosphate, or adenine also inhibited gluconeogenesis. alpha, beta-Methylene-ATP, a nonmetabolizable structural analogue of ATP, did not affect the rate of gluconeogenesis. Intracellular ATP levels were increased by externally added ATP or adenosine, but ATP-to-ADP ratios in the cytosolic and mitochondrial compartments were diminished. Malate and phosphoenolpyruvate contents were decreased by extracellular ATP or adenosine. Our results show that inhibition of gluconeogenesis by high levels of extracellular ATP may be mediated by adenosine derived from ATP catabolism at the plasma membrane. PMID- 1750577 TI - Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia. AB - To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure. PMID- 1750578 TI - Glucose loading prevents freezing injury in rapidly cooled wood frogs. AB - The wood frog (Rana sylvatica) is the most commonly studied of ten species of freeze-tolerant vertebrates. Under natural (i.e., slow) rates of cooling, freezing initiates the production of the cryoprotectant glucose, which is mobilized from the liver and distributed to tissues throughout the body. Rapid cooling during freezing is injurious to wood frogs, probably because cryoprotectant production and mobilization are inhibited. To test this hypothesis, we investigated whether rapid-cooling injury is reduced if exogenous glucose is experimentally introduced to tissues before freezing. Glucose-loaded and control (saline-injected) wood frogs were rapidly cooled during freezing to 2.5 degrees C and subsequently assayed for injury at both cellular (erythrocyte) and neuromuscular (behavioral reflex) levels. Rapid cooling produced substantial hemolysis in control frogs, but erythrocyte injury was significantly reduced in glucose-loaded frogs. Similarly neuromuscular injury was significantly higher in control frogs than in glucose-loaded frogs. These findings suggest that rapid cooling injury results from an inadequate production and distribution of endogenous glucose during freezing. Furthermore, the inverse relationship between the degree of freezing injury and the quantity of exogenous glucose present strongly implicates glucose as a cryoprotectant in R. sylvatica. PMID- 1750579 TI - Dietary fat, hypothalamic glutamate decarboxylase, and food intake of streptozotocin-diabetic rats. AB - The association among changes in glucose status, glutamate decarboxylase (GAD) activity, and food intake was evaluated in several hypothalamic areas of streptozotocin-diabetic rats fed a low- (12% of calories as fat) or high-fat diet (59% of calories as fat). Control rats consumed approximately 90 kcal/24 h of either diet, whereas diabetic rats consumed approximately 150 kcal/24 h of the low-fat diet and approximately 100 kcal/24 h of the high-fat diet. At the end of the study, diabetic rats fed the high-fat diet weighed more and had higher retroperitoneal fat depot weights (P less than 0.05) than diabetic rats fed the low-fat diet. In diabetic rats, GAD activity was 15-20% higher in the ventromedial nucleus (P less than 0.01) but similar to controls in the lateral hypothalamus, paraventricular nucleus, and area postrema. Diet did not affect GAD activity in the brain areas studied. The increase in ventromedial nucleus GAD activity was not associated with the level of food intake and was the likely result of altered glucose homeostasis in diabetic rats. PMID- 1750580 TI - alpha-Chloralose alters autonomic reflex function of the lower urinary tract. AB - The effects of alpha-chloralose on the micturition reflex were evaluated using an efficiently voiding decerebrate cat model. At laparotomy cannulas were introduced into the urethra and/or bladder for measurement of urethral perfusion pressure and/or bladder pressure during bladder filling and voiding. After establishment of efficient voiding in the anesthetic-free decerebrate cat, chloralose, 50 mg/kg iv, was administered. Parameters assessed before and after anesthetic included bladder pressure at peak of contraction (voiding pressure), intravesical pressure at onset of bladder contraction (threshold pressure), contraction amplitude, duration of bladder contraction, bladder volume at onset of bladder contraction (volume threshold), and residual bladder volume after voiding (postvoid residual). In addition to these parameters, preparations with intact bladder urethra and with divided bladder-urethra were used to assess effects of chloralose on voiding efficiency and coordination between bladder and urethra, respectively. Chloralose significantly reduced voiding pressure, contraction amplitude, and voiding efficiency. Neither vehicle for the chloralose nor sympathetic denervation of the lower urinary tract affected these reductions. Chloralose had no effect on direct contraction of the bladder and urethra produced by intra-arterial acetylcholine (25-100 micrograms). Chloralose converted the synergic bladder and urethral responses during voiding to dyssynergic responses. Neuromuscular blockade with gallamine, 10 mg/kg iv, improved voiding efficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750581 TI - Dietary modulation of intestinal nutrient transport in the teleost fish tilapia. AB - Tilapia (Oreochromis mossambicus) were fed a diet with either 60% carbohydrate (70% grain-4% fish meal) or 17% carbohydrate (11% grain-65% fish meal) for greater than or equal to 4 wk. Intestinal uptake of radiolabeled acetate, D glucose, and L-proline was measured in brush-border membrane vesicles. As expected, fish fed high carbohydrate had significantly higher D-glucose uptake than those fed low carbohydrate [maximal uptake rate (Vmax), respectively, 84.2 +/- 18.2 vs. 37.4 +/- 10.9 pmol.mg protein-1.s-1; n = 4 batches of vesicles in each case; t test, P less than 0.025]. The change in glucose transport was specific, because in the same batches of vesicles there was no significant diet effect on carrier-mediated uptake of L-proline or acetate. Also as expected, dietary modulation of carrier-mediated transport was effected primarily by alterations in Vmax and not apparent Michaelis constant (Km); Km was not significantly altered by diet for either D-glucose (high carbohydrate vs. low carbohydrate, respectively, 0.34 +/- 0.17 vs. 0.12 +/- 0.03 mM; P greater than 0.2), L-proline (respectively, 0.10 +/- 0.03 vs. mM 0.13 +/- 0.05), or acetate (respectively, 4.8 +/- 1.4 vs. mM 6.5 +/- 2.2). PMID- 1750582 TI - Neural and humoral effects on hindlimb vascular resistance of ducks during forced submergence. AB - Circulating catecholamines increase by three orders of magnitude in forced submerged ducks; their role in promoting vascular resistance was studied using vascular perfusion of hindlimbs. Perfusion pressure and blood flow were recorded simultaneously in hindlimbs of ducks during forced submergence. One leg was perfused with blood mixtures devoid of catecholamines (test leg) and compared with the other autoperfused leg. Perfusion pressures in test legs perfused with hyperoxic and hypocapnic blood or with hypoxic and hypocapnic blood were not significantly different from those in the matching autoperfused legs. However, when test legs were perfused with hypercapnic blood, regardless of whether blood was hypoxic or hyperoxic, perfusion pressures were significantly lower than in autoperfused legs. Adding catecholamines to test legs perfused with hypoxic and hypercapnic blood, after 3 min submergence, significantly enhanced vasoconstriction. Hypercapnia acts directly on the peripheral vascular beds and impairs the neurally mediated vasoconstriction during submergence, while circulating catecholamines restore peripheral vasoconstriction. Thus circulating catecholamines are needed to compensate for the depressant action of hypercapnia on neurally mediated vasoconstriction. PMID- 1750583 TI - Isoflurane field anaesthesia at extreme temperatures. PMID- 1750584 TI - The potential hazards of using iodine as an antiseptic solution. PMID- 1750585 TI - Supplementary oxygen--potential for disaster. PMID- 1750586 TI - Dose-response relationship and time course of action of Org 9426. A new muscle relaxant of intermediate duration evaluated under various anaesthetic techniques. AB - The dose-response relationship of Org 9426, its time course of action and the reversibility of the residual block by neostigmine have been investigated in 100 patients undergoing various anaesthetic techniques. The dose-response was measured immediately following induction of anaesthesia. Doses of Org 9426, required for 50% and 90% depression of the twitch height, were 202 and 328 micrograms.kg-1, respectively. The clinical duration of the maintenance doses, 150 micrograms.kg-1, ranged from 9.5 to 13.4 min and from 12.8 to 18.9 min for the first and fifth maintenance doses, respectively. Spontaneous recovery indices (25%-75%) were between 9.5 and 16.7 min; neostigmine methylsulphate administered at 25% recovery of the twitch height promptly reversed the residual block. No side effects were observed. The extent of the influence of the anaesthetic on the time course of Org 9426 appears to be fractional considering the variation of the time course within the separate groups. PMID- 1750587 TI - Effects of epidural diamorphine on the somatosensory evoked potential to posterior tibial nerve stimulation. AB - We have studied the effects of the epidural administration of diamorphine 0.1 mg/kg at the L3-4 interspace on somatosensory evoked potentials in the cervical epidural space before corrective surgery for idiopathic adolescent scoliosis. A further eight patients in whom anaesthesia was maintained with a propofol infusion acted as a control group. Epidural diamorphine had no effect on the latency or amplitude of the evoked potentials. We conclude that epidural diamorphine is a suitable technique to use in scoliosis surgery because of its lack of effect on neurophysiological variables, although the potential respiratory problems need investigation. PMID- 1750588 TI - Analgesic efficacy of controlled-release dihydrocodeine. A comparison of 60, 90 and 120 mg tablets in cold-induced pain. AB - A prospective, double-blind, single-dose placebo-controlled four-part crossover study of 12 healthy volunteers was carried out to compare the analgesic efficacy of controlled-release dihydrocodeine tablets 60, 90 and 120 mg (DHC Continus tablets, Napp Laboratories) in cold-induced pain. Subjects received each of the four treatments in a random order using a latin square design. On each of the four study days, the volunteers performed cold pressor tests, before dose and again at 4, 8 and 12 hours after dose. Subjects rated their pain continuously over a 120-second period using a visual analogue scale. At 4 hours there was a significant reduction in pain in subjects who received 120 mg or 90 mg tablets compared with placebo, and in subjects who received 120 mg tablets compared with those who received 60 mg tablets. At 8 hours, 120 mg and 90 mg dihydrocodeine were still better than placebo. There was no significant difference in side effects between treatments. PMID- 1750589 TI - Pain following thoracotomy. A randomised, double-blind comparison of lumbar versus thoracic epidural fentanyl. AB - Fifty-eight patients scheduled for elective thoracotomy were randomly allocated to receive fentanyl by either the thoracic or the lumbar epidural route for postoperative analgesia. The infusion rate was adjusted to optimise analgesia. Dose adjustment, pain assessment and the incidence of side effects were monitored by a blinded observer at set times over the 24 hour study period. Similar pain scores were obtained in both groups at all assessment times. In addition, there was no significant difference in dose requirements or incidence of side effects between the two groups. There appears little justification for the use of the generally less familiar, and potentially more dangerous, thoracic approach when fentanyl alone is infused into the epidural space following thoracotomy. PMID- 1750590 TI - Intra-ocular pressure changes using the laryngeal mask airway and tracheal tube. AB - Intra-ocular pressure was measured before and throughout airway establishment with either the laryngeal mask airway or tracheal tube. Similar measurements were made on removal of either airway and the amount of coughing noted in the first minute after removal. There was a significantly smaller increase in intra-ocular pressure (p less than 0.001) using the laryngeal mask airway, both on placement and removal, than with the tracheal tube. Postoperative coughing was significantly reduced using the laryngeal mask airway (p less than 0.001). There was a significantly greater rise in heart rate using the tracheal tube (p less than 0.01) probably related to an increased cardiovascular response. The laryngeal mask airway is recommended as an alternative to tracheal intubation in routine and emergency intra-ocular surgery. PMID- 1750591 TI - Protamine--the need to determine the dose. Comparison of a simple protamine titration method with an empirical dose regimen for reversal of heparinisation following cardiopulmonary bypass. AB - A simple method of protamine titration using the Hemochron system was compared with an empirical dose protocol for reversal of heparinisation following cardiopulmonary bypass in 40 patients undergoing elective myocardial revascularisation. Protamine titration revealed a wide range for protamine requirement and resulted in a significant reduction in protamine dose compared with the empirical dose protocol (p less than 0.01). Heparin reversal was assessed as adequate in all patients. The titration technique was easy and straightforward to use in the operating theatre. PMID- 1750592 TI - Acute tolerance from benzodiazepine night sedation. AB - The hypothesis that benzodiazepine night sedation causes acute tolerance to benzodiazepine sedation given the following morning was examined in six volunteers in a double blind, randomised, crossover study. Before each of three study days, subjects received midazolam 15 mg or flunitrazepam 2 mg or placebo as oral night sedation. They were then given intravenous midazolam 5 mg the following morning and the resulting sedative effects examined, using an observers sedation scale and a psychomotor test battery (critical flicker fusion frequency, digit-symbol substitution, reflex time, tapping test and a visual analogue sedation scale). Although a consistent pattern emerged with the greatest degree of sedation following the placebo night sedation and the least degree of sedation following the midazolam, with flunitrazepam intermediate, no statistically significant differences were present between the three treatment groups. The results indicate that single use of benzodiazepine night sedation is not an important influence on benzodiazepine requirements for intravenous sedation. PMID- 1750593 TI - Hysteria. A cause of failure to recover after anaesthesia. AB - Hysteria as a cause of failure to recover consciousness following general anaesthesia is a rare event. This case report describes such an instance in a young, healthy 22-year-old female suffering severe dental phobia who was undergoing dental conservation. The literature is reviewed and a summary of the possible physiological mechanisms involved is given. PMID- 1750594 TI - Double-blind testing fails to confirm analgesic response to extradural morphine. AB - We report two patients with chronic non-malignant pain in whom morphine given intravenously via a patient-controlled analgesia system produced partial pain relief but was accompanied by severe side effects. Open administration of epidural morphine resulted in complete pain relief with minimal side effects and the patients were considered as candidates for implanted opioid delivery systems. However, when the epidural morphine was given in a double-blind and placebo controlled manner, morphine did not produce greater analgesia than placebo and no dose-response relationship was seen. These cases show that careful investigation is necessary before proceeding to implanted systems and that changing the route did not improve the analgesia:side effect balance for morphine in these patients. PMID- 1750595 TI - Reversible renal failure following opioid administration. AB - A patient who received intravenous papaveretum during and after operation developed anuria and biochemical evidence of impaired renal function in the first 6 hours after surgery. Administration of naloxone 0.4 mg was associated with a sustained improvement in urine output. Mean arterial pressure did not change significantly. The impairment of renal function may have been related to high plasma concentrations of codeine, one of the constituents of papaveretum. PMID- 1750596 TI - A case of malignant hyperthermia? AB - An acute episode of a malignant hyperthermia-like syndrome is described which occurred after suxamethonium and isoflurane anaesthesia in a 41-year-old healthy male patient undergoing a minor elective hand operation. Dantrolene therapy rapidly reversed the life-threatening signs. Laboratory results appeared to confirm the suspicion of malignant hyperthermia. However, the in vitro contracture test, which was carried out according to the standards of the European Malignant Hyperthermia Group, was equivocal. PMID- 1750597 TI - Extradural analgesia and previous spinal surgery. A radiological appraisal. AB - Extradural block was performed in a nulliparous patient with previous spinal surgery. Epidurographic evidence explains the rapid onset and extensive sensory block obtained. PMID- 1750598 TI - A low-flow to-and-fro system. Laboratory study of mixing of anaesthetic and driving gases during mechanical ventilation. AB - The insertion of a long deadspace tube between an anaesthetic breathing system and a ventilator produces only imperfect separation of the breathing system gas from the driving gas. This laboratory study has investigated different connecting tubes to establish the maximum tidal volume possible before ventilator gas contaminates the gas in a low-flow to-and-fro system (fresh gas flow 1 litre/minute). A larger volume tube enables the use of larger tidal volumes, and plastic corrugated tubes are slightly better than black rubber corrugated tubes in this respect. The maximum tidal volume possible without contamination decreases as ventilatory rate increases, but the maximum minute volume is increased. A 22 mm plastic corrugated tube of internal volume 1.5 litres should be adequate for clinical use with the to-and-fro system described in this study at a fresh gas flow of 1 litre/minute. PMID- 1750599 TI - Evaluation of a small soda lime canister in a to-and-fro system. AB - The main disadvantages of the to-and-fro system (the bulky canister and the progressive increase in apparatus deadspace) may be overcome by the use of a smaller canister. In this laboratory study, we have evaluated a 160 g canister in a low-flow to-and-fro system (fresh gas flow 1 litre/minute). Two carbon dioxide productions of 150 and 200 ml/minute were simulated. The mean times to exhaustion, defined here as a 0.5 kPa rise in end-tidal PCO2, were 112 and 79 minutes in the 150 and 200 ml/minute carbon dioxide groups respectively. Ventilation to normacapnia or hypocapnia did not affect the times to exhaustion. The soda lime absorbed 16 litres of carbon dioxide before exhaustion, and this was not affected by minute volume or carbon dioxide production. A small soda lime canister is suitable for carbon dioxide absorption in a low-flow to-and-fro system for ventilated adults. PMID- 1750600 TI - Environmental contamination during tracheal suction. A comparison of disposable conventional catheters with a multiple-use closed system device. AB - The extent of airborne environmental bacterial contamination which occurs following tracheal suction has been investigated in patients undergoing intermittent positive pressure ventilation in the intensive therapy unit. Two methods of performing suction, one using a conventional open technique and one using a closed system (Stericath), have been compared. Significantly lower levels of environmental contamination were observed when the closed system was used. PMID- 1750601 TI - Mortality associated with anaesthesia. A case review study. AB - The review is based on an analysis of anonymous case record material at the Medical Protection Society's London Office for the 5-year period 1982-1986, in which death was associated with anaesthetic procedures. A total of 25 cases were analysed. The principal events which resulted in death were failed intubation, drug-related problems and problems with equipment. The principal contributory factors were inadequate supervision, inadequate pre-operative assessment and failure of communication. The present review suggests that supervision and training of junior staff, decision-making by senior staff and patterns of communication both within and between specialties are areas which should be selected for further research. PMID- 1750602 TI - Acid aspiration prophylaxis in morbidly obese patients: famotidine vs. ranitidine. AB - Famotidine and ranitidine were compared as agents for the prevention of acid aspiration syndrome in 32 morbidly obese patients undergoing vertical banded gastroplasty. Single-dose oral famotidine or double-dose oral ranitidine were administered on a random basis before surgery. Gastric contents were aspirated through a gastric tube, manually aided by the surgeon with the abdomen open. Mean (SD) gastric volumes were 13.8 ml (6.7) and 12.1 ml (13.0) for the famotidine and ranitidine groups, respectively. Mean (SD) gastric pH values were 6.2 (1.5) and 6.8 (1.5), respectively. There were no significant differences between the groups and no patient was considered 'at risk' (pH less than 2.5 and gastric volume greater than 25 ml). We conclude that single-dose oral famotidine and double-dose oral ranitidine are equally effective for preventing acid aspiration syndrome in morbidly obese patients. PMID- 1750603 TI - Diamorphine analgesia after caesarean section. Comparison of intramuscular and epidural administration of four dose regimens. AB - In a randomised double-blind study, the efficacy, duration of action and side effects of five diamorphine analgesia regimens following Caesarean section are described. The time to next analgesia was shorter in the 5 mg intramuscular group (3.53 hours) than in any of the four epidural groups: 5 mg (5.7 hours, p = 0.007), 2.5 mg (4.76 hours, p = 0.103), 5 mg with adrenaline 1/200,000 (7.2 hours, p = 0.001) and 2.5 mg with adrenaline 1/200,000 (6.05 hours, p = 0.007). Multiple regression analysis showed that the addition of adrenaline significantly increased the duration of action of epidural diamorphine (p less than 0.05). The 5 mg dose with adrenaline showed no advantage when compared with 2.5 mg with adrenaline (p = 0.16). No serious side effects were reported in any group. PMID- 1750604 TI - Inhaled nebulised fentanyl for postoperative analgesia. AB - The effects of three concentrations of inhaled nebulised fentanyl citrate solution given for postoperative pain relief were studied. Each of 30 patients inhaled one dose of 3 ml of solution nebulised over 9 min. A combined analysis of pain relief, time to further analgesia and effect on respiratory frequency showed the highest concentration (318 micrograms/ml fentanyl base) to be more effective (p less than 0.01) than the two lower concentrations (159 micrograms/ml and 64 micrograms/ml) which were indistinguishable from each other. There were no major side effects. This study provides evidence for the efficacy and safety of inhaled fentanyl for postoperative analgesia. Estimation of the delivered doses did not support the hypothesis that fentanyl is more effective by this route compared with other parenteral routes. Further studies are required to improve the method of delivery and investigate the pharmacodynamic features of this technique. PMID- 1750605 TI - Parents in the anaesthetic room. A questionnaire survey of parents' reactions. AB - One hundred and forty-one parents were asked to complete a questionnaire about their reactions after accompanying their child during induction of anaesthesia. Of 139 respondents, 99% believed that their presence was of benefit to their child, and 95% believed that they helped the anaesthetist. The degree of anxiety experienced by the parent did not significantly affect this view, nor was the degree of anxiety affected by the method of induction chosen by the anaesthetist. PMID- 1750606 TI - Intubation through the laryngeal mask. PMID- 1750607 TI - Cricoid pressure and the laryngeal mask airway. PMID- 1750608 TI - Facilitation of the insertion of the laryngeal mask. PMID- 1750609 TI - Use of the laryngeal mask in a patient with an unstable fracture of the cervical spine. PMID- 1750610 TI - Cardiovascular effects of epidural local anaesthetics. PMID- 1750611 TI - Cost of intensive care. PMID- 1750612 TI - Pulse oximetry in pulseless patients. PMID- 1750613 TI - A false compatibility. PMID- 1750614 TI - Glycopyrronium and reflex bradycardia on elevation of zygoma. PMID- 1750615 TI - Pre-operative removal of dentures. PMID- 1750616 TI - Parents do not always want to be present at induction of anaesthesia of their children. PMID- 1750617 TI - Chickenpox pneumonia: NAB before IPPV? PMID- 1750618 TI - Higher pressure ventilation and the Bain coaxial breathing system. PMID- 1750619 TI - Penlon Nuffield Anaesthesia Ventilator Series 200. The case for vigilance? PMID- 1750620 TI - Atrial fibrillation after electroconvulsive therapy. PMID- 1750621 TI - Temperature and drug potency. PMID- 1750622 TI - Block of epidural needle by blood clots. PMID- 1750623 TI - Anaesthesia for laparoscopic cholecystectomy. PMID- 1750624 TI - Dangerous repairs. PMID- 1750625 TI - Sensitivity to papaveretum in Gilbert's disease. PMID- 1750626 TI - Wound infiltration and caesarean section. PMID- 1750627 TI - It would have been the anaesthetist's fault. PMID- 1750628 TI - Kuhn's endotracheal tube. PMID- 1750629 TI - Carbon monoxide poisoning. AB - Carbon monoxide is a common domestic and industrial poison which may be lethal. Survivors can develop permanent neuropsychiatric disability. The mechanisms of toxicity are poorly understood and the traditional criteria used to determine the severity of the poisoning have low predictability. Oxygen is the recommended antidote to carbon monoxide, but it appears that oxygen under hyperbaric conditions repeated either daily or as indicated by the patient's condition may be required to provide an effective dose. A reliable marker of the severity of carbon monoxide poisoning is urgently needed so that trials of alternative regimens can proceed. PMID- 1750630 TI - Granulocyte transfusions--a review for the intensive care physician. AB - In order to achieve the maximum therapeutic benefit in the treatment of malignancies, doses of chemotherapeutic agents are pushed to the point of severe marrow toxicity. This aggressive therapy can lead to iatrogenic complications including haemorrhage and sepsis due to the depletion of platelets and granulocytes. Prior to the advent of platelet transfusions, haemorrhage was the leading cause of death in these patients. Advances in blood banking and the availability of platelet transfusions have markedly decreased the incidence of fatal haemorrhage. As a result, infection has become the leading cause of death in patients with marrow failure. Although the risk of infection in patients with neutropenia has been well documented, the role of granulocyte transfusions in the treatment and prevention of these infections remains controversial. This paper will attempt to review the currently available literature regarding granulocyte procurement techniques and the efficacy of granulocyte transfusions. PMID- 1750631 TI - Gastric emptying in the postpartum period. AB - We measured gastric emptying, using the technique of paracetamol absorption, in eight women on their first and third postpartum day. Gastric emptying was rapid and there was no difference between the first and third day in the time to peak plasma concentration of paracetamol. Six women returned after six weeks for a further study. Gastric emptying was still rapid but the metabolism of paracetamol appeared to be slower than that found during the immediate postpartum period. These findings suggest that fluid fasting guidelines in patients more than one day postpartum need not be different from those in non-pregnant patients. PMID- 1750632 TI - Single versus double occlusive dressing technique to minimize infusion thrombophlebitis: Vialon and Teflon cannulae reassessed. AB - Infusion thrombophlebitis is the commonest complication of intravenous cannulation. This study was undertaken to prospectively evaluate a double occlusive dressing technique and a new cannula, bismuth oxide-Teflon (Critikon Inc., Aust.), comparing it to Vialon (Deseret Medical Inc., Utah, USA). The study group of two hundred patients had a 16 gauge intravenous cannula inserted in theatre using a standard technique. The incidence of thrombophlebitis was determined on a daily basis. Cannula tips were sent for culture on removal. Vialon was found to be superior to Teflon after day 1. Although a double occlusive dressing technique increased the duration of cannulation (50.9 vs. 41.9 hours, P less than 0.05), there was no difference in the incidence of thrombophlebitis. Neither cannula material nor dressing technique had an influence on the results of cannula tip culture (6% incidence). There was no evidence of bacteraemia in any case. PMID- 1750633 TI - The efficacy of antivenom in prevention of cardiovascular depression and coagulopathy induced by brown snake (Pseudonaja) species venom. AB - The efficacy of antivenom in prevention of cardiovascular depression and coagulopathy induced by Brown Snake species (Pseudonaja textilis, Pseudonaja affinis) was investigated in anaesthetised mechanically ventilated dogs. Venom and antivenom in variable amounts were incubated together at 37 degrees C for 30 minutes prior to intravenous injection. The dose of antivenom required to prevent severe cardiovascular depression and coagulopathy induced by Pseudonaja textilis venom was 25 times the current recommended dose for clinical use. A tenfold dose of antivenom was required to neutralise similar effects induced by Pseudonaja affinis venom. Large amounts of antivenom may be required in clinical use if coagulopathy or cardiovascular depression are present after envenomation by species of the Brown Snake genus. PMID- 1750634 TI - Diclofenac in combination with opiate infusion after joint replacement surgery. AB - The effect of intramuscular diclofenac or placebo on analgesia obtained and on opiate and antiemetic requirements was observed in a randomised double-blind study of sixty patients receiving continuous intravenous papaveretum. Those patients receiving diclofenac required less papaveretum (P = 0.001) than those receiving placebo. They also had lower visual analogue pain scores (VAS) at four hours (P less than 0.05) and decreased requirement for antiemetics (P less than 0.02). No gastrointestinal complications were observed in either group and blood loss did not differ significantly between the two. PMID- 1750635 TI - Interpleural bupivacaine infusion compared with intravenous pethidine infusion after cholecystectomy. AB - Twenty-six cholecystectomy patients received either an interpleural infusion of bupivacaine (Group B, n = 12) or an intravenous infusion of pethidine (Group P, n = 14) for management of postoperative pain over a three-day period. Patients in Group P experienced a significantly (P less than 0.05) greater incidence of total side-effects (146) than patients in Group B (66). Pain scores (VAS) and responses to a pain questionnaire were similar for both groups; however, within Group B improvement in mean VAS scores at rest with time were more sustained. Similar reductions in FEV1 and FVC from preoperative values occurred for both groups, while for Group P there were significant (P less than 0.05) changes in arterial blood gases (increase in PCO2, decrease in PO2) over two days postoperatively. Patients in Group P recorded longer times to passing flatus and unaided mobilisation (P less than 0.05), and required a significantly greater number of additional medications (anti-emetics and analgesics) over the postoperative period (41 vs 29, P less than 0.05). PMID- 1750636 TI - Use of the cell saver during elective abdominal aortic aneurysm surgery- influence on transfusion with bank blood. A retrospective survey. AB - One hundred and two patients undergoing elective abdominal aortic aneurysm repair and admitted to ICU at RPAH in 1989/90 were studied. In forty patients a cell saver was used during the operative procedure (Group CS) while in the remaining sixty-two patients intraoperative blood loss was drained and discarded conventionally (Group NCS). Preoperative ASA grade and postoperative APACHE score were similar in these two groups. The amount of bank blood transfused intraoperatively was less in Group CS than in Group NCS (0.6 +/- 0.2 vs 3.3 +/- 0.3 units) (mean +/- SEM) (P less than 0.0001). The total amount of bank blood transfused during hospital admission was also less in Group CS (1.5 +/- 0.4 vs 4.8 +/- 0.4 units, P less than 0.0001). Of Group CS, 22 patients (55%) received no bank blood compared to two patients (3%) in Group NCS. There was no difference between the groups with respect to postoperative haemoglobin and creatinine levels. ICU stay was similar in both groups. We conclude that use of the cell saver reduces perioperative bank blood transfusion in elective abdominal aortic surgery. PMID- 1750637 TI - Caudal blockade for postoperative analgesia: a useful adjunct to intramuscular opiates following emergency lower leg orthopaedic surgery. AB - The efficacy of a single caudal epidural injection of bupivacaine 20 ml 0.5% following emergency orthopaedic surgery to the lower leg and ankle was investigated. Forty adult patients were studied, randomised to either the caudal or control group. The mean 24 hour postoperative papaveretum consumption was significantly reduced in the caudal group. Analogue pain scores as assessed in a double-blind manner were also significantly reduced in this group. The duration of analgesia after caudal blockade was approximately eight hours as estimated by the average time to the first dose of papaveretum. Our study demonstrates that caudal blockade represents an effective adjunct to intramuscular opiates following this type of surgery. PMID- 1750638 TI - Variation in the blood concentration/analgesic response relationship during patient-controlled analgesia with alfentanil. AB - The effect of supplementing postoperative patient-controlled analgesia (PCA) with a mandatory fixed-rate infusion was studied using alfentanil. Patients were assigned by lottery to receive alfentanil PCA with a bolus of 200 or 300 mcg or alfentanil PCA with a bolus of 100 or 200 mcg plus an infusion of 900 mcg/hr, such that ten patients received each treatment. Seven patients receiving PCA only, compared to two in the groups receiving infusion, were withdrawn due to inadequate pain relief (0.1 greater than P greater than 0.05). One patient receiving PCA only was withdrawn because of a low respiratory rate, whereas three patients receiving PCA plus infusion developed respiratory depression. Patients prescribed PCA plus infusion received significantly more alfentanil but did not describe less pain than patients prescribed PCA only. The blood alfentanil concentration immediately prior to demands was significantly higher in the PCA plus infusion groups. These results suggest that during PCA therapy the drug prescription influences the blood concentration associated with satisfactory analgesia. PMID- 1750639 TI - CPAP, effective respiratory support in patients with AIDS-related Pneumocystis carinii pneumonia. AB - Human Immunodeficiency Virus (HIV) related Pneumocystis carinii pneumonia (PCP) associated with severe respiratory failure is an increasingly common problem in major centres and is associated with a high mortality in previous and recent studies. Early in the epidemic, alternatives to invasive intensive care treatment were utilized in our institution and found to be successful. When respiratory failure developed, mask CPAP was used instead of intubation and ventilation. A retrospective review of 175 cases of HIV infected patients with confirmed first presentation PCP was undertaken. Treatment with our protocol resulted in an overall hospital mortality of 9%. Those patients who did not require supplemental oxygen or respiratory support had no in-hospital mortality. The group who required supplemental oxygen had a mortality of 10%. If respiratory failure supervened (severe respiratory distress, PaO2 less than 50 mmHg, SaO2 less than 90% on mask oxygen), CPAP was introduced. The mortality in this group was 22%. Only two patients were admitted to the intensive care unit for respiratory support after failure of CPAP. Both patients were intubated and received intermittent positive pressure ventilation (IPPV). Both patients died. PMID- 1750640 TI - Shoulder manipulation to facilitate central vein catheterization from the external jugular vein. AB - Manipulation of the shoulder to facilitate passage of J-wires past the clavicle during external jugular vein catheterization was tested prospectively in 111 adult patients undergoing cardiac surgery. On 10 of 25 occasions when the wire would not pass into the thorax, manipulation of the shoulder then allowed the wire to pass. PMID- 1750641 TI - Epidural abscess associated with postoperative epidural analgesia. PMID- 1750642 TI - Propofol and convulsions--the evidence mounts. PMID- 1750643 TI - Interpleural anaesthesia in the management of upper limb ischaemia. A report of three cases. PMID- 1750644 TI - Two cases of naloxone-induced pulmonary oedema--the possible use of phentolamine in management. PMID- 1750645 TI - Acute anaemia to a haemoglobin of 14 g.l-1 with survival. PMID- 1750646 TI - Development of a high block in an infant during an epidural bupivacaine infusion. PMID- 1750647 TI - Urgent airway access--an indication for percutaneous tracheostomy? PMID- 1750649 TI - Diaphragmatic pacing: an alternative to long-term mechanical ventilation. AB - Electrical percutaneous stimulation of the phrenic nerves was first employed in 1948 by Sarnoff to provide temporary artificial ventilation in patients with respiratory failure. However, the technique was limited by development of infection around the electrode. Short-term radiofrequency stimulation of the phrenic nerves was first utilised by Glenn in 1964 and adapted to long-term use in patients with central hypoventilation in 1968 and with traumatic quadriplegia in 1972. The technique employed alternate pacing of each hemidiaphragm with high frequency stimulation (25-30 Hz) with a respiratory rate of 12 to 17 per minute which, in a series of 17 quadriplegic adults, although initially successful, was self-limiting because of eventual damage to the nerves and diaphragms. More recently, continuous bilateral simultaneous low frequency (up to 8 Hz) stimulation with a respiratory rate of 5 to 9 per minute has not induced myopathic changes. This phenomenon has been attributed to: 1. the conversion of the mixture of slow and fast twitch fibres in the diaphragm to a uniform population of fatigue resistant fibres induced by low frequency stimulation, and 2. the reduction in the total current necessary to achieve adequate gas exchange when both diaphragms contract simultaneously with the less frequent stimulation at lower energy. Diaphragmatic pacing has been applied to infants and children with emphasis on the selection of patients and optimum setting of stimulus parameters. This communication presents a case report of diaphragmatic pacing in a child with a review of the principles of application. The advantages and disadvantages compared to mechanical ventilation are also discussed. PMID- 1750648 TI - A comparison of five devices for the bedside monitoring of heparin therapy. AB - Five instruments were tested for their capacity to monitor heparin therapy on whole blood at the bedside. The instruments were 512 Coagulation Monitor (Ciba Corning), Thrombotrack (Nycomed), Automated Coagulation Timer (Hemotec), Hemochron-ACT and Hemochron-APTT (International Technidyne Corporation). Fifty subjects with various levels of heparinisation were tested on each instrument and were also assayed for antithrombin III, fibrinogen, haematocrit, platelet count and plasma heparin level. The results were compared with a reference APTT performed on the Automated Coagulation Laboratory 300R (Instrumentation Laboratories). The Hemochron-ACT correlated least well. The Hemotec and Thrombotrack were unsuitable in a clinical setting because of pipetting requirements, although the Thrombotrack did correlate well with the reference parameters. The 512 Coagulation Monitor was the simplest to use, but its maximum response corresponded to the midpoint of the reference APTT therapeutic range. The Hemochron-APTT was simple to use, had an adequate response range and correlated well with reference parameters. PMID- 1750650 TI - The second Geoffrey Kaye oration. PMID- 1750651 TI - Modified intravent LMA. PMID- 1750652 TI - Using a peripheral nerve stimulator as a nerve locator. PMID- 1750653 TI - Vomiting after strabismus surgery. PMID- 1750654 TI - Awareness. PMID- 1750655 TI - Ulco carbon dioxide absorber. PMID- 1750656 TI - Epidural LA/opioid. PMID- 1750657 TI - Complications of epidural analgesia. PMID- 1750658 TI - Tubeless anaesthesia for microlaryngeal surgery? PMID- 1750659 TI - A 'too close to the door' knob. PMID- 1750660 TI - Pulse oximetry or pulse photometry. PMID- 1750661 TI - Inserting the laryngeal mask. PMID- 1750662 TI - Scavenging hazard. PMID- 1750663 TI - A spuriously low end-tidal carbon dioxide. PMID- 1750664 TI - Anabolic steroids and anaesthesia. PMID- 1750665 TI - Anaesthesia system errors. PMID- 1750666 TI - Chemical procedures for C-terminal sequencing of peptides and proteins. PMID- 1750667 TI - Lysis and fractionation of Mycobacterium paratuberculosis and Escherichia coli by matrix solid-phase dispersion. AB - A novel method for the lysis and subsequent fractionation of bacterial constituents from Mycobacterium paratuberculosis strain 19698 (M. paratuberculosis) and Escherichia coli strain DH5 alpha utilizing the technique of matrix solid-phase dispersion (MSPD) is described. Bacteria were blended with octadecylsilyl (C18) derivatized silica to obtain cellular lysis. The blended material was used to prepare a column which was sequentially eluted with solvents of increasing polarity. Fractionation of cellular components was confirmed by analysis of the solvent extracts. The possible applicability of the MSPD technique as a general method for the lysis and fractionation of bacterial components is proposed. PMID- 1750668 TI - Preparative in vitro mRNA synthesis using SP6 and T7 RNA polymerases. AB - A method for preparative in vitro mRNA synthesis is presented. The method makes it possible to generate several hundred RNA copies per molecule of linearized DNA template. The protocol is applicable to the synthesis of RNAs of differing lengths (from 200 to 3000 bases), and both SP6 and T7 RNA polymerases can be used. The transcription can be scaled up to at least 6-12 ml, yielding 4.5-18 mg of homogeneous biologically active mRNA. PMID- 1750669 TI - Biotinylated basic fibroblast growth factor is biologically active. AB - Basic fibroblast growth factor (bFGF) was modified by biotinylation via amino group substitution, using biotin-N-hydroxysuccinimide ester at molar reaction ratios of 20, 200, and 2000 per bFGF molecule (respectively named bio-bFGF.20, bio-bFGF.200, and bio-bFGF.2000). The biotinylated bFGF derivatives, bio-bFGF.20 and bio-bFGF.200, conserved the same affinity for heparin as native bFGF, in contrast to bio-FGF.2000 which lost this property. Bio-bFGF.20 and bio-bFGF.200 were as effective as native bFGF in their capacity to compete with 125I-bFGF for binding to bFGF receptor on bovine brain membranes. The biological activity of these bFGF derivatives was tested on CCL39 cells; bio-bFGF.20 and bio-bFGF.200 were as able as native bFGF to promote growth of CCL39. PMID- 1750670 TI - Single-sweep polarographic investigation of concanavalin A and its interaction with polysaccharide. AB - A simple, rapid, and sensitive single-sweep polarographic method has been developed for investigation of concanavalin A (con A) and its interaction with selected polysaccharides. In a solution containing 0.001 M 2,2'-bipyridine, 0.015 M hexamethylenetetramine, and 0.1 M sodium chloride, con A exhibits a single sweep polarographic wave, and the cathodic peak potential is -1.50 V (vs SCE). The peak current varies linearly with con A concentration over a range of 1.0 x 10(-8) to 1.2 x 10(-7) M by derivative single sweep polarography. A preliminary discussion on properties of the con A polarographic wave has been made. In addition, it has been demonstrated that single sweep polarography can be a useful method for studies on interactions of con A with its complementary polysaccharides in solution. PMID- 1750671 TI - Detection of poly(ADP ribose) polymerase in crude extracts by activity-blot. AB - We have recently devised an activity-blot procedure permitting the detection, on the same nitrocellulose sheet, of the functional poly(ADP ribose) polymerase (PARP) activity as well as the immunostained active peptide(s) after renaturation of the transferred protein(s). Using this technique we have analyzed the PARP activity in higher and lower eukaryotes directly on crude extracts from cell cultures. This procedure has been extended also to in situ screening of bacterial colonies expressing the PARP enzymatic activity. PMID- 1750672 TI - Enzymatic determination of total CO2 in freeze-clamped animal tissues and plasma. AB - An enzymatic method for measuring total carbon dioxide content in freeze-clamped animal tissues is described. Total carbon dioxide content [TCO2] was defined as the sum of the dissolved CO2, the bicarbonate concentration, and the carbonate concentration. Tissue was extracted in 80% methanol, 20 mM 2-amino-2-methyl-1 propanol, pH 9.5 at 25 degrees C and homogenized in a 1.5-ml Sardstat screw-top test tube containing 0.5-mm glass beads and a minibead beater. Total CO2 was determined as bicarbonate/carbonate by monitoring the oxidation of NADH at 340 nm using the coupled assay of phosphoenolpyruvate carboxylase (EC 4.1.1.31) and malate dehydrogenase (EC 1.1.1.37). In the coupled assay system, 1 mumol of bicarbonate/carbonate consumed is equivalent to the oxidation of 1 mumol NADH at 340 nm. The assay medium comprised 50 mM 2-amino-2-methyl-1-propanol, pH 9.0 at 25 degrees C, 5 mM phosphoenolpyruvate (PEP), 0.25 mM NADH, 5 mM MgCl2, 5 mM mercaptoethanol, 0.02% bovine serum albumin, 10 mM oxamate, PEP carboxylase (0.5 units/ml), and malate dehydrogenase (0.5 units/ml). The total CO2 content measured in freeze-clamped rat heart, liver, brain, and skeletal muscle was 20.53 +/- 0.64, 17.34 +/- 0.67, 17.00 +/- 0.48, 16.06 +/- 0.53 mumol/g wet wt tissue, respectively (n = 5). The total CO2 in the crusher muscle of the lobster was found to be 5.0 +/- 0.33 mumol/g wet wt. Total CO2 was also enzymatically measured in arterial plasma from four chronically cannulated male wistar rats and was 24.65 +/- 1.81 mumol/ml plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750673 TI - Optimization of an alcian blue dot-blot assay for the detection of glycosaminoglycans and proteoglycans. AB - A modification of a method for the detection of proteoglycans on positively charged nylon was adapted for use in a dot-blot assay and improved. Different dot blot membranes were tested and variations in the Alcian blue staining solution (including pH, critical electrolyte concentration, and ionic strength) were explored. With modifications, we were able to eliminate interferences by other polyanions such as DNA or proteins. We were able to detect glycosaminoglycans and proteoglycans down to the 10 ng range. Furthermore, our assay is compatible with high concentration of urea (up to 7 M) used in classic proteoglycans extraction methods and is a useful tool to monitor the isolation of proteoglycans by anion exchange and gel filtration chromatography. It is technically easier, faster, more sensitive, and more specific than previously published methods and can be adaptated as a quantitative assay using a scanning densitometer with a linear range of detection from 10 to 100 ng of glycosaminoglycans. PMID- 1750674 TI - Correction for incomplete labeling in the measurement of distance distributions by frequency-domain fluorometry. AB - Measurements of time-resolved fluorescence are now being used to recover conformational distributions of biological macromolecules. The fluorescence data of the donor are easily corrupted by incomplete labeling of the macromolecules by the acceptor. In the present paper we describe a general procedure to correct for incomplete acceptor labeling in the determination of distance distributions from frequency-domain measurements of the donor fluorescence decay kinetics. The method can also be used to determine the extent of acceptor labeling. Simulated data were used to determine the effect of incomplete labeling on resolution of the distance distribution and the effect on the recovered distributions if one fails to account for incomplete labeling by the acceptor. The expressions and implemented algorithm were verified using known mixtures of donor-control and donor-acceptor pair molecules, which simulated the presence of a donor population lacking the acceptor. Finally, we present data on the distance distributions between two labeled sites in myosin S1 (Cys-697 to Cys-707) where it was not possible to obtain complete labeling of the acceptor site. PMID- 1750675 TI - Analysis of glutathione S-transferase from human liver by isoelectric focusing in a urea minigel system. AB - A method for the rapid analysis of isozyme subunits of glutathione transferase (GST) from human liver is described. Following purification of enzyme protein to electrophoretic homogeneity on columns of GSH-agarose, pooled transferase fractions were concentrated by ultrafiltration and subjected to further fractionation and analysis by urea-isoelectric focusing in minigels using a Hoefer Mighty Small II electrophoresis system. These methods combined with immunoblotting techniques permitted the resolution, detection, and eventual analysis of up to six different subunits of the alpha isozyme of human GST and at least three to four different forms of the pi isozyme of the transferase rapidity, accuracy, and sensitivity of the methodology may prove useful to the analysis and quantification of GST subunits in biopsies of malignant human tissue and to the development of effective chemotherapeutic regimens. PMID- 1750676 TI - Bulk purification of isochorismic acid by low-pressure octadecyl (C18) reverse phase liquid chromatography. AB - Partially purified isochorismate synthase (EC 5.4.99.6) from Klebsiella pneumoniae 62-1 was used to produce bulk quantities (3.4-6.8 mg) of isochorismate from chorismate. A new, preparative, low-pressure liquid chromatographic method for the purification of isochorismate was used; a (1.0 X 13.0 cm) octadecyl (C18) reverse-phase column with a discontinuous, stepped methanol gradient as eluent. The recovery of isochorismate was quantitative and its purity was verified by HPLC using a butyl (C4) reverse-phase column. This chromatographic method is superior to those previously described. PMID- 1750677 TI - Se-(8-azidoadenosyl)[75Se]selenomethionine as a photoaffinity label for S adenosylmethionine binding proteins. AB - A method is described for the synthesis and purification of the photoaffinity label Se-(8-azidoadenosyl)[75Se]selenomethionine. This photoaffinity label can be used to specifically and covalently label the S-adenosylmethionine binding site of proteins that use this cofactor, as exemplified by labeling of thioether methyltransferase. By utilizing the gamma-emitting isotope of selenium, Se-(8 azidoadenosyl)[75Se]selenomethionine eliminates the need for the impregnation of acrylamide gels with fluorographic enhancers and dilution of liquid samples into scintillation cocktails, as is required with the commonly used methyl-3H-labeled and 35S-labeled S-(8-azidoadenosyl)methionine. PMID- 1750678 TI - Application of a new slot comb to electrophoretic analysis. AB - In the present experiment, a new slot comb was designed in order to form a wide and sloped sample well on the stacking gel of electrophoresis. Using this slot comb, a gradient of the reagent layer of interest can be easily formed transversely on the gel that is perpendicular to the direction of electrophoresis. Thus, the protein sample overlaid on the agent migrates across the gradient layer during electrophoresis to produce a continuous electrophoretic band reflecting the interaction between the protein and reagent. This new slot comb (tentatively called slope comb) was applied to the following two experiments. In the first experiment, in combination with this comb and a reducing agent, 2-mercaptoethanol, the reducing steps of cross-linked axonemal proteins with o-iodosobenzoic acid (OIBA) were analyzed electrophoretically, enabling visualization of the reducing pattern of each axonemal protein in a single experiment. The results obtained indicate that alpha and beta tubulins are cross-linked differently by OIBA. In the second experiment, the formation of the Ca2+ gradient layer using this slope comb could electrophoretically differentiate the Ca2+ sensitivity of three Ca(2+)-binding proteins. PMID- 1750679 TI - Synthesis, chromatographic purification, and analysis of isomers of biliverdin IX and bilirubin IX. AB - Neutral solvent systems were developed to isolate the alpha, beta, gamma, and delta isomers of biliverdin IX dimethyl ester by TLC. The individual free acids of biliverdin IX were obtained by saponification of the corresponding dimethyl esters. The bilirubin IX isomers were prepared by reducing the corresponding biliverdin IX isomers with NaBH3CN. Starting from a pure biliverdin IX dimethyl ester, the corresponding free acid of biliverdin IX or bilirubin IX was available within 3-4 h. Preparation of spectrally pure bile pigment required final TLC on acid-cleaned neutral TLC plates. The absorption spectra of the free acids and dimethyl esters of biliverdin IX in methanol showed a broad band at about 650 nm and a sharp band at about 375 nm. The long-wave-length band was extremely sensitive to the presence of strong acid. A 10-fold molar excess of HCl caused a 35- to 50-nm shift of the absorption maximum to longer wavelengths and near doubling of the maximum absorption. The molar absorption coefficients of biliverdins were identical for each free acid and dimethyl ester pair. In each case, Beer's law was followed in both methanol and acidified methanol. Methanol also proved to be a suitable solvent for spectroscopic determination of the non alpha isomers of bilirubin IX. The wavelength of maximum absorption and molar absorption coefficient of each dipyrrolic ethyl anthranilate azo pigment derived from the various bilirubin IX isomers are also reported. PMID- 1750680 TI - Photoduplication and fluorescence measurement in polyacrylamide gel electrophoresis. AB - A simple method of photoduplication of gel electrophoresis, visualized with fluorescent reagents, is described. The procedure is convenient and rapid and requires no camera or expensive equipment. Using electrophoresis duplicating paper (Kodak), positive prints suitable for documentation or publication may be obtained. With usual photographic paper, negative prints may be obtained, allowing reliable measurement by scanning. The technique may be applied to protein or nucleic acid electrophoresis. PMID- 1750681 TI - Europium(III) cryptate: a fluorescent label for the detection of DNA hybrids on solid support. AB - We report here a new detection method for DNA hybrids on dot blots. The process utilizes DNA or oligonucleotide probes labeled with biotin, followed by recognition with a conjugate of streptavidin and europium cryptate, a time resolved fluorescent label. Unlike the other lanthanide chelates, this label is an organic molecule embedding a europium ion into an intramolecular cavity. This structure has a better stability in diluted assay media, a good sensitivity even on solid support, and an elevated fluorescence lifetime which allows elimination of most of the background generated by other species present in the assay medium. This procedure is quantitative and detects down to 2 amol of a model DNA, which is similar to other nonisotopic (especially colorimetric) methods. The main advantages of this method are easy automation, quantitation, and rapidity of measurements. PMID- 1750682 TI - Analysis of cardiolipin molecular species by high-performance liquid chromatography of its derivative 1,3-bisphosphatidyl-2-benzoyl-sn-glycerol dimethyl ester. AB - Cardiolipin (CL, 1,3-bisphosphatidyl-sn-glycerol) is a four-acyl-chain phospholipid whose molecular species composition cannot be analyzed by standard procedures. Here we report a method to resolve the molecular species of CL by high-performance liquid chromatography of its derivative 1,3-bisphosphatidyl-2 benzoyl-sn-glycerol dimethyl ester. The CL derivative was characterized by 1H nuclear magnetic resonance spectroscopy, ultraviolet (uv) spectroscopy, thin layer chromatography, and fatty acid analysis. The derivatization procedure did not change the fatty acid profile and provided a virtually complete conversion to the highly apolar, uv-visible product. In HPLC separations, recorded by 228 nm absorbance, a linear correlation was found between the area of individual peaks and their amount of lipid phosphorus. Bovine heart CL was resolved into 11 molecular species of which 6 (together accounting for 97 mol%) could be identified. The molecular species of bovine heart CL feature a linear relationship between their logarithmic retention time and their double bond number. PMID- 1750683 TI - Stepped potential microcoulometry of ferritin. AB - A coulometric method for measuring the redox potentials of ferritins and the rates of reduction of the iron core is reported. The half-reduction potential, Eo', of the protein is determined from the coulomb-applied potential curve. This curve is obtained from the difference between the curves for the mediator plus protein and the mediator alone. The coulomb-applied potential curves are generated by stepping the potential in increments over the region of interest and measuring the charged passed following each step. The method is reasonably fast, enabling the redox potential to be determined in 1 day, and gives Eo', values for mediators and the protein that are in good agreement with literature values. PMID- 1750684 TI - Homogeneous enzyme immunoassay for lipoic acid based on the pyruvate dehydrogenase complex: a model for an assay using a conjugate with one ligand per subunit. AB - A homogeneous enzyme immunoassay for lipoic acid was developed by using an enzyme ligand conjugate containing only one ligand per enzyme subunit. Theoretical studies have shown that the traditional use of multisubstituted enzyme-ligand conjugates has limited the detection limits and sensitivity obtainable with these assays. The use of conjugates with a smaller number of ligands should allow for improved assays. The pyruvate dehydrogenase complex was chosen for this study because each polypeptide chain of dihydrolipoyl transacetylase contains one lipoic acid as a covalently attached prosthetic group. Thus, the naturally occurring enzyme can be considered as an enzyme-lipoic acid conjugate. Anti lipoic acid antibodies were developed in New Zealand White rabbits to be used as the analyte-specific binders. Association and binder dilution curves were prepared in order to optimize the reagent concentrations and the analytical conditions. Unexpected inhibition by free lipoic acid resulted in a biphasic dose response curve with a detection limit of 5 x 10(-6) M lipoic acid. This technique has several advantages over previous electrochemical and chromatographic techniques for lipoic acid determination. PMID- 1750685 TI - Spectrophotometric method for the determination of microquantities of lactic acid in biological material. AB - A simple spectrophotometric method for the determination of microquantities of lactic acid is described. Lactic acid was quantitatively oxidized to acetaldehyde by cerium(IV) under prescribed conditions. Oxidation was terminated by reducing cerium(IV) to cerium(III) with nitrite. The acetaldehyde was reacted with copper ions and oxalydihydrazide under alkaline conditions to form an intense blue complex which is measured spectrophotometrically. The developed citrate-phosphate borate-sodium hydroxide alkalizing reagent enhanced color stability by removing cerium from solution and also ensured extremely low blank values. Beer's law was followed over the range 0 to 150 micrograms of lactate. The method was successfully applied to the routine determination of lactate in silage and blood. PMID- 1750686 TI - Assay of myosin light chain kinase activity by high-performance liquid chromatography using a synthetic peptide as substrate. AB - The most popular method to determine the activity of myosin light chain kinase is to measure the radioactivity incorporated from [gamma-32P]ATP into phosphoryl accepting substrates. In this paper, we report a new method for determination of myosin light chain kinase activity without using radioisotopes. Synthetic peptides and nonradiolabeled ATP were used as substrate, and the peptide substrate was phosphorylated by myosin light chain kinase purified from chicken gizzard. After terminating the reaction, the reaction mixture was directly injected into a reversed-phase HPLC column without pretreatment, separated with the isocratic solvent system of acetonitrile-H2O-trifluoroacetic acid, and monitored at 220 nm uv absorbance. The reaction rate was determined from the peak areas of phosphorylated and unphosphorylated peptides. One chromatographic separation was achieved within 9 min, and the analysis could be repeated successively more than 100 times without washing the column. Using this method, we measured the differential inhibition of myosin light chain kinase by various inhibitors. With the aid of an automatic injector, the HPLC method with synthetic peptide enables us to handle many samples quickly and is useful for screening new myosin light chain kinase inhibitors. PMID- 1750687 TI - Affinity electrophoresis used for determination of binding constants for antibody antigen reactions. AB - The use of affinity electrophoresis in agarose gels for determination of binding constants for the interaction of antigens with monoclonal antibodies is exemplified for monoclonal anti-human serum albumin and anti-alpha 1-fetoprotein antibodies. The calculated binding constants are verified by independent binding assays. The electrophoretic separation of antigen-antibody complexes of different stoichiometry is also demonstrated. Thus, affinity electrophoresis represents an alternative method for both qualitative and quantitative assessment of antigen antibody interactions. PMID- 1750688 TI - Measurement and analysis of triplet-state lifetimes by multifrequency cross correlation phase and modulation phosphorimetry. AB - In this paper we describe a novel approach to study the triplet-state lifetimes by a conventional multifrequency cross-correlation phase and modulation apparatus. The analysis of phase and modulation data of eosin-labeled band 3 erythrocyte ghosts revealed the existence of two phosphorescence lifetime values of 2700 and 750 microseconds, with a fractional contribution of 78 and 22%, respectively, which are in good agreement with those reported in the literature. Differential polarization phase analysis, which facilitates the study of the rotational properties of band 3, provided data in good agreement with those reported in the literature. The method proposed in this paper to study the radiative emission from the triplet state may represent a convenient alternative to the pulse laser flash technique. PMID- 1750689 TI - Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation. AB - The recent development of near-infrared time- and frequency-resolved tissue spectroscopy techniques to probe tissue oxygenation and tissue oxygenation kinetics has led to the need for further quantitation of spectroscopic signals. In this paper, we briefly review the theory of light transport in strongly scattering media as monitored in the time and frequency domains, and use this theory to develop algorithms for quantitation of hemoglobin saturation from the photon decay rate (delta log R/delta t) obtained using time-resolved spectroscopy, and from the phase-shift (theta) obtained from frequency-resolved, phase-modulated spectroscopy. To test the relationship of these optical parameters, we studied the behavior of delta log R/delta t and theta as a function of oxygenation in model systems which mimicked the optical properties of tissue. Our results show that deoxygenation at varying hemoglobin concentrations can be monitored with the change in the photon decay kinetics, delta delta log R/delta t in the time-resolved measurements, and with the change in phase-shift, delta theta, in the frequency-resolved technique. Optical spectra of the adult human brain obtained with these two techniques show similar characteristics identified from the model systems. PMID- 1750690 TI - Sequence-specific DNA affinity chromatography: application to the purification of EcoRI and SphI. AB - Several rapid and effective methods have been described to obtain restriction endonucleases suitable for commercial exploitation. However, lengthy and laborious protocols have been necessary to obtain homogeneous enzymes. We now report the use of sequence-specific DNA affinity chromatography to purify restriction endonucleases to near homogeneity. Restriction endonucleases EcoRI and SphI from the microorganisms Escherichia coli RY 13 and Streptomyces phaeochromogenes, respectively, were purified to near homogeneity employing a two step procedure which involves DNA-cellulose chromatography and oligonucleotide ligand affinity chromatography. PMID- 1750691 TI - Rotating disc electrode characterization of immobilized glucose oxidase. AB - The kinetic properties of glucose oxidase (EC 1.1.3.4) which has been covalently immobilized to a rotating glassy carbon electrode surface have been investigated. Analysis of the rotation rate dependence of the hydrogen peroxide-derived current suggests that oxygen mass transport to the enzyme-electrode surface is rate controlling at low rotation rates. Only as the diffusion layer approaches zero thickness (i.e., infinitely fast rotation rate) does mass transport become unimportant. A diffusion-free glucose Km for air-saturated buffer is found to be 66 mM using this methodology. The importance of mass transport restrictions in two-substrate enzymes such as glucose oxidase is discussed in the context of biosensor design. PMID- 1750692 TI - A two-cycle immunoprecipitation procedure for reducing nonspecific protein contamination. AB - A two-cycle immunoprecipitation procedure is described that markedly reduces nonspecific protein contamination occurring during the precipitation of hepatic lipase from rat H4 hepatoma cells. In this method, the precipitation of immune complexes during both cycles is achieved by utilizing a sodium dodecyl sulfate (SDS)-washed preparation of lyophilized Staphylococcus aureus cells (Staph A); this washed preparation effectively removes Staph A contaminants without compromising the ability to bind immune complexes. Following initial immunoprecipitation of the antigen, the Staph A/IgG/antigen complex containing coprecipitated nonspecific proteins was dissociated with SDS. Triton X-100 was added to the dissociated immunoprecipitate at a concentration (by weight) of at least 5 parts Triton X-100 to 1 part SDS. A second cycle of immunoprecipitation was then initiated by addition of fresh antibody, followed by Staph A precipitation of immune complexes and analysis by SDS-polyacrylamide gel electrophoresis. The two-cycle procedure is shown to be reproducible and suitable for the quantitative determination of relative amounts of hepatic lipase. The procedure described here is generally applicable to the immunoprecipitation of other antigens. PMID- 1750693 TI - A continuous spectrophotometric method for the determination of diphenolase activity of tyrosinase using 3,4-dihydroxymandelic acid. AB - A continuous spectrophotometric method for the rapid determination of diphenolase activity of tyrosinase is described. It uses 3,4-dihydroxymandelic acid (DOMA) as the substrate of tyrosinase and measures the final product, 3,4 dihydroxybenzaldehyde (DOBA). The spectrum of this product shows a bathochromic displacement of its absorbance maximum when the pH increases. The optimization of the method is described by using tyrosinase from several biological sources, whose enzymatic activities show different optimal pH. Thus, the enzymatic activity of mushroom tyrosinase was assayed at pH 7.5 and monitored at 350 nm (epsilon 350 pH 7.5 (DOBA) = 15,200 M-1 cm-1), whereas the spectrophotometric experiments with grape tyrosinase were carried out at pH 3.0 and monitored at 310 nm (epsilon 310 pH 3.0 (DOBA) = 9200 M-1 cm-1). The method for mushroom tyrosinase was found to be 50-fold more sensitive than the commonly used dopachrome assay, whereas for grape tyrosinase the method was found to be threefold more sensitive than the commonly used o-quinone production assay. The great solubility and stability of the chromophoric product, DOBA, as well as its high molar absorptivities at any pH, enable the method to be employed to determine the diphenolase activity of tyrosinase from different biological sources. PMID- 1750694 TI - Quantitation of uracil in rodent diet. AB - Feeding of high levels of uracil to laboratory rodents results in the formation of calculi in the lumen of the urinary bladder. This urolithiasis stimulates cellular proliferation in the bladder and has been used in studies of two-stage carcinogenesis. Quantitation of uracil in rodent diet was achieved by extraction from the diet with ammonium hydroxide. The extract was applied to a strong anion exchange solid-phase extraction column. Uracil is not retained on this matrix which adsorbs the majority of contaminants in the extract. The uracil was quantitated by HPLC on an ODS microbore column (100 x 2 mm internal diameter) eluted at 0.5 ml/min with 200 mM KH2PO4, pH 3.5, at 30 degrees C. Three structurally related pyrimidine bases, cytosine, uracil, and thymine, showed increasing retention on this column/solvent combination, thereby demonstrating selectivity of the analysis. Recovery of uracil was 76-90% with lower values observed when dietary levels of uracil were in excess of 4.5%. PMID- 1750695 TI - Operation of ion-selective electrode detectors in the sub-Nernstian/linear response range: application to flow-injection/enzymatic determination of L glutamine in bioreactor media. AB - A novel approach for eliminating positive errors from endogenous ionic interferences when using ion-selective electrodes as detectors in flow-injection enzyme-based blosensing configurations is described. The method involves using a high background level of interfering ions in the sample diluent/carrier stream to convert the normally logarithmic potentiometric sensor into a linear detector over a given concentration range of primary ions. A split-stream single-detector arrangement provides a convenient means to compensate for varying levels of background interferent ions in the injected samples. One portion of the split stream passes directly to the ion-electrode detector, yielding a signal linearly related to the concentration of endogenous primary ions in the sample. The second portion of the split sample is delayed while passing through an immobilized enzyme that generates electrode detectable primary ions in proportion to the concentration of the substrate analyte in the sample. Two linear equations with two unknowns describe the twin potentiometric responses observed. The concept is demonstrated by the accurate determination of L-glutamine in hybridoma bioreactor media via the use of an ammonium-ion-selective membrane electrode detector and immobilized glutaminase enzyme. PMID- 1750696 TI - Increased analytical precision in the hollow cathode discharge emission source by improved discharge current control. AB - A significant improvement in the precision of the hollow cathode as an emission source is reported. Precision of 1% or less has been observed several times over periods of several hours. An average long-term stability of 4.3% for Ll and 6.0% for Na in the emission signal from microsamples (less than 50 nL) deposited in the hollow cathode discharge source is reported. The improved precision is attributed primarily to the introduction of electronics that hold the discharge current more nearly constant and to the shielding of all wiring to the source from the power supply. A current-controlled switch that is capable of driving a hollow cathode discharge in either dc or pulsed mode is described. This switch is capable of generating current pulses as short as 2 microseconds through a resistive load and greatly improves the discharge stability and repeatability at turn-on in both the dc and pulsed modes. The characteristics of pulses produced by this switch are presented; however, analytical performance is reported only for the dc mode. Temporal current plots are presented for the new instrumentation and compared to plots taken with commonly used current-controlled power supplies. Instrumentation, operation, and sample preparation procedures are described. Typical temporal profiles of the emission signal from microsamples deposited in AI and stainless steel hollow cathodes are given. PMID- 1750697 TI - Trace-concentration detection of cobalt in a liquid flow cell by degenerate four wave mixing using low-power off-resonant laser excitation. AB - Optical phase conjugation by degenerate four-wave mixing (D4WM) in an absorbing metal-ion solution using a low-power argon-ion laser as the excitation source is demonstrated. This nonlinear laser technique can be used as a sensitive analytical spectroscopic method for trace-concentration measurement of metal ions in a small-volume continuously flowing analyte cell. Several important characteristics are discussed, including the effects of solvent properties, excitation wave-length, laser intensity, and analyte absorptivity on signal intensity. Detection of 0.26 ng (4.4 pmol) of cobalt inside the laser probe volume of 0.14 microL is reported using an excitation wavelength that is 136 nm away from the maximum absorption wavelength of the analyte solution. The minimum absorbance measured in our D4WM experiment is 2.0 X 10(-5) without complex formation for cobalt. The D4WM detection sensitivity, in terms of the concentration-absorptivity product, is 4.05 X 10(-4) cm-1 for cobalt(II) in ethanol. Our preliminary detection sensitivity compares favorably with other laser-based spectrometric methods. This nonlinear laser technique is applicable to both fluorescing and nonfluorescing analytes. PMID- 1750698 TI - Detection of biomolecules on surfaces using ion-beam-induced desorption and multiphoton resonance ionization. AB - Multiphoton resonance ionization (MPRI) has been combined with ion-beam-induced desorption to examine a set of thermally labile biological molecules present on surfaces. Specifically, we have examined films of adenine and beta-estradiol, molecules with a rigid skeletal backbone. In both of these cases, molecular ions could be produced efficiently without cooling the neutral molecules into their ground vibrational state. We have also studied other more fragile molecules such as tryptamine, tryptophan, phenylalanine, and serotonin. The base peak in the mass spectra of these molecules is fragment ions formed by losses of the amine side chains. Even with this fragmentation, however, it is possible to achieve sensitivity limits that are many orders of magnitude greater than for secondary ion mass spectrometry, without preparing the samples in special matrices. For serotonin, detection limits of 40 fmol on the surface of a silicon target are achievable. The results also yield a linear relation between the serotonin base fragment ion intensity and the known surface concentration. PMID- 1750699 TI - Optimization of the fragmentation in a frit-fast atom bombardment ion source for the sequencing of peptides at the picomole level. AB - Peptides derived from enzymatic digestions (cathepsin D and trypsin) were characterized and amino acid sequences determined by using their LC/MS spectra. A Frit-FAB interface that produces extensive peptide fragmentation and permits amino acid sequencing at the low picomole level is described for a model antigen, Staphylococcus aureus nuclease (Nase), and an enzyme of unknown structure, yeast aminopeptidase B. The amino acid sequences of peptides derived from digestion of Nase with cathepsin D (a relatively nonspecific endoprotease) were readily deduced and have provided insights into the nature of antigen processing. Frit FAB LC/MS spectra of the Nase peptides contained a sufficient number of fragment ions to conclusively identify peptides with a mass below 2000 Da. Capillary LC/MS provided a means for the separation and identification of these enzymatically derived peptides in a fraction of the time that would have been required by gas phase Edman sequence analysis. The optimized Frit-FAB experiment was consequently evaluated for the partial characterization of aminopeptidase B recently purified to homogeneity from Saccharomyces cerevisiae. Sequence-specific ions observed in the Frit-FAB mass spectra of these tryptic peptides were identical with those commonly observed in high-energy collision-induced dissociation (CID) spectra and included side-chain fragment ions that differentiated leucine from isoleucine. These fragment ions were used to deduce entire amino acid sequences for several of the tryptic peptides. PMID- 1750700 TI - Determination of dissolved selenium species in environmental water samples using isotope dilution mass spectrometry. AB - In order to clarify the species composition of selenium in environmental water samples, analytical methods have been developed for the selective determination of different chemical forms of this element (selenite, selenate, and organic species including trimethylselenonium) using isotope dilution mass spectrometry (IDMS). The species analysis was made possible by means of chromatographic separation procedures and an 82Se-enriched selenate, selenite, and trimethylselenonium spike for the isotope dilution process. The total selenium concentration was determined after decomposition of organic compounds with a HNO3/HCIO4 mixture. Selenium was measured in the mass spectrometer by producing negative Se- thermal ions for detection. Precise determination at the parts-per trillion level was achieved. This new methodology was applied to different types of natural water samples (groundwater, pond water, river water, moorland lake water) with total selenium concentrations in the range of 200 pg/g to 15 ng/g. Selenite and selenate have been the only detected species in most of the investigated samples, with selenate dominating all except one. In samples with high contents of dissolved organic carbon, however, different organoselenium compounds including trimethylselenonium ions were additionally quantified in the range of 10-95 pg/g. In these cases, the sum of all selenium species agreed well with the independently determined total element concentration. PMID- 1750701 TI - Determination of ethylenethiourea in crops using particle beam liquid chromatography/mass spectrometry. AB - Several food crops were analyzed for residues of ethylenethiourea (ETU), a suspect thyroid and liver carcinogen present in EBDC fungicides, using a commercial particle beam (PB) LC/MS method. The PB/LC/MS detection limits for ETU in crops (5 ppb, 1.25 ng) are comparable to those obtained by LC with electrochemical detection. Spectra obtained from crop samples containing as little as 5 ng of ETU were matched with the NBS library reference EI spectrum. Isotopically labeled ETU was used as an internal standard for quantitation and determination of recoveries. No enhancement of molecular ion signal intensity from unlabeled ETU was observed upon coelution with the isotopically labeled variant. This MS method permits detection of ETU with increased selectivity without compromising sensitivity. PMID- 1750702 TI - Liposome flow injection immunoassay: model calculations of competitive immunoreactions involving univalent and multivalent ligands. AB - The use of liposomes as detectable reagents in solid-phase immunoassays has been explored in a flow injection immunoanalysis (FIIA) system. Model calculations are presented for FIIA based on the competitive binding of univalent analyte and multivalent liposomes to immobilized antibodies. Parameters such as binding constants, concentrations of liposomes and antibody, and steric hindrance are considered for their relative effects on detectable liposome signal response to analyte concentrations. Qualitative comparisons of the model with the experimental data are made. PMID- 1750703 TI - Prediction of gas chromatographic relative retention times of anabolic steroids. AB - The prediction of gas chromatographic relative retention times (RRTs) of anabolic steroids, used in the doping control of athletes, was performed by a quantitative structure-retention relationship (QSRR) and multiple linear regression analysis study. A nine-variable model was generated with a multiple correlation coefficient R = 0.991 and relative standard error of less than 3%. Preliminary results indicated that the application of the model, especially in the prediction of RRTs of metabolites of the anabolic steroids, will be helpful. PMID- 1750704 TI - Capillary gel affinity electrophoresis of DNA fragments. AB - The incorporation of an affinity ligand within a polyacrylamide gel provides a general means of manipulating the selectivity of capillary gel electrophoresis separations. As an example of this approach, high resolution of DNA restriction fragments by capillary gel affinity electrophoresis has been achieved by adding a soluble intercalating agent, ethidium bromide, to the gel-buffer system. A migration model has been developed that can be used for selectivity optimization. Various parameters, such as ligand concentration and applied electric field, have been examined in terms of their influence on retention and selectivity of different-size DNA molecules. From this study, high-resolution separations have been developed with efficiencies as high as 10(7) theoretical plates per meter. PMID- 1750705 TI - Determination of halocarbons in drinking water by direct aqueous injection gas chromatography. PMID- 1750706 TI - Immunocytochemical localization of follicle regulatory-protein (FRP) in testis. AB - Follicle regulatory protein (FRP) can exert paracrine control over follicular development. It is synthesized by the granulosa cells of the developing follicles and was localized in the cytoplasm of the mural cells by immunocytochemistry. When administered to male dogs and rats, FRP causes impairment of spermatogenesis. In the intact male rat, it has been postulated that FRP manifests its effects at a stage prior to the conversion of testosterone to dihydrotestosterone. Sertoli cells of the seminiferous tubules are implicated in testosterone metabolism. Furthermore, Sertoli cells in male gonads are regarded as the counterpart of granulosa cells in ovaries. The exact source of FRP in the male is not known. Therefore, it was of interest to study the localization of FRP in the male gonads. Testicular sections of the pig, dog, cat, rat, mouse, monkey, and man were immunocytochemically stained with monoclonal antibody to porcine FRP of ovarian origin. Sections of pig ovaries were used as controls throughout the study. Specificity of immunocytochemical localization was established by preabsorption. FRP antibody predominantly localized to the interstitial compartment of the pig testis. In the seminiferous tubules, FRP localization was limited to basal spermatogonia and Sertoli cells of tubules at few specific stages of spermatogenesis. The study also showed that the monoclonal antibody against porcine FRP is species-specific. Antibody binding was found only in pig testis, whereas tissues from the cat, dog, mouse, rat, monkey, and man did not display any immunocytochemical reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750707 TI - FSH in testes of marmosets during development: immunocytochemical localization and de novo biosynthesis. AB - Immunocytochemical localization of FSH was carried out in various cell types of marmoset testes during development using antisera generated against intact as well as beta-subunit of human FSH. Significant differences in the intensity as well as distribution of FSH in various cell types were observed in neonatal, pubertal, and adult marmosets. Intensity of staining in Leydig cells was maximum at day 1 and in adults (1-3 years), whereas it was minimum at 3 months. In seminiferous tubules (Sertoli cells), FSH was present in trace amount until puberty and subsequently increased at maturity. Further studies demonstrate de novo biosynthesis of FSH-like moiety in vitro by testicular tissue, which was age dependent. PMID- 1750708 TI - Experimental analysis of blood vessel development in the avian wing bud. AB - Shortly after its appearance, the avian limb bud becomes populated by a rich plexus of vascular channels. Formation of this plexus occurs by angiogenesis, specifically the ingrowth of branches from the dorsal aorta or cardinal veins, and by differentiation of endogenous angioblasts within limb mesoderm. However, mesenchyme located immediately beneath the surface ectoderm of the limb is devoid of patent blood vessels. The objective of this research is to ascertain whether peripheral limb mesoderm lacks angioblasts at all stages or becomes avascular secondarily during limb development. Grafts of core or peripheral wing mesoderm, identified by the presence or absence of patent channels following systemic infusion with ink, were grafted from quail embryos at stages 16-26 into the head region of chick embryos at stages 9-10. Hosts were fixed 3-5 days later and sections treated with antibodies that recognize quail endothelial cells and their precursors. Labeled endothelial cells were found intercalated into normal craniofacial blood vessels both nearby and distant from the site of implantation following grafting of limb core mesoderm from any stage. Identical results were obtained following grafting of limb peripheral mesoderm at stages 16-21. However, peripheral mesoderm from donors older than stage 22 did not contain endothelial precursors. Thus at the onset of appendicular development angioblasts are present throughout the mesoderm of the limb bud. During the fourth day of incubation, these cells are lost from peripheral mesoderm, either through emigration or degeneration. PMID- 1750709 TI - Occurrence of epidermal growth factor-binding sites during differentiation of cementoblasts and periodontal ligament fibroblasts of the young rat: a light and electron microscopic radioautographic study. AB - Occurrence of epidermal growth factor (EGF)-binding sites during differentiation of cementoblasts and periodontal ligament (PDL) fibroblasts was investigated using radioautography after I. V. injection of 125I-EGF to 14-day-old rats. During differentiation of cementoblasts, a very low level of EGF-binding sites was present on the mesenchymal cells in dental follicle proper, precementoblasts, and cementoblasts. On the other hand, during differentiation of PDL fibroblasts, numerous EGF-binding sites were observed on the undifferentiated paravascular cells and on the perifollicular mesenchymes representing the major source of PDL fibroblast precursor cells. Also heavy labeling was observed throughout their differentiation to PDL fibroblasts, as well as during full synthetic activity as mature cells. Quantitative analysis of the light microscopic radioautographs revealed that these cells demonstrated approximately 4 grains per 100 microns 2 of cell area. These results suggest that EGF plays an important role in differentiation of PDL fibroblasts, but not in that of cementoblasts. Furthermore, the well-known in vivo effect of EGF in producing precocious eruption of teeth may be a consequence of a more extensive effect of EGF throughout differentiation of PDL fibroblasts as well as during full synthetic activity as mature cells. PMID- 1750710 TI - Anionic site and immunogold quantitation of heparan sulfate proteoglycans in glomerular basement membranes of puromycin aminonucleoside nephrotic rats. AB - Renal glomerular basement membranes (GBMs) exhibit a charge-selective barrier, consisting of heparan sulfate proteoglycan (HSPG) that restricts the passage of anionic molecules into the urine. Previous efforts to localize the HSPG core protein within various layers of the GBM have been contradictory. Furthermore, attempts to correlate proteinuria in several disease states with a decrease in anionic sites of HSPG core protein have yielded conflicting results. When antibodies to HSPG from the EHS tumor matrix [anti-(EHS) HSPG] and GBMs [anti (GBM) HSPG] were used together with immunogold to label renal tissues from puromycin aminonucleoside nephrotic (PAN) rats, immunolabeling results indicated that a portion of the protein core recognized by anti-(EHS) HSPG was significantly reduced, while immunolabeling with anti-(GBM) HSPG was only slightly reduced in early PAN. Anionic sites (stained with the cationic probe, polyethyleneimine) within the lamina rara externa of the GBM remained unaltered throughout the course of PAN. PMID- 1750711 TI - The kidney of tapirs: a macroscopical study. AB - The renal cortex of tapirs, water-loving primordial ungulates, was continuous, nonlobed, and about 80% of renal mass in adult and 71% in term-neonate. In the neonates even the peripheral glomeruli were moderately mature. Tapirus bairdi had about 4 million glomeruli per kidney and T. pinchaque about 3 million smaller glomeruli. Number of glomeruli per gm of cortex was 12,444 in T. bairdi and 13,400 in T. pinchaque. Cortical loops were common in the medullary rays. The medulla was the simple crest-type. The terminal collecting ducts (T.C.D.) opened separately at the crest and not into a tubus maximus. The "outer stripe" of the outer medulla apparently was telescoped into the deep cortex. The medullary loops turned at a thick portion and at nearly all levels of the medulla. The medullary crest was lined by urothelium which extended into the ends of the T.C.D. Otherwise the T.C.D. were made of columnar epithelium. The pelvic urothelium was continuous with that of the medullary crest at the dorsal and ventral fornices. The fornices were well within the inner medulla. Hence only inner medulla could be exposed to pelvic urine. The hilar arteries, unlike the other two perissodactyl families (rhinoceri and equids), passed through the cortico medullary (C-M) border and some large arteries and veins passed through the outer medulla to and from the C-M border without branches or tributaries. Unlike kidneys with a medullary crest in diverse eutherian mammals, tapirs lacked pelvic extensions along the major intrarenal blood vessels and thus lacked pelvic intervascular eminences. PMID- 1750712 TI - Distribution of actin isoforms within cells of the seminiferous epithelium of the rat testis: evidence for a muscle form of actin in spermatids. AB - Recently, a cDNA that coded for an enteric smooth muscle gamma-actin (SMGA) that was expressed in post-meiotic mouse testicular cells was identified. To determine the cellular location(s) of the protein encoded by this cDNA, this SMGA was probed for by immunocytochemistry in the cells of the seminiferous epithelium with two different monoclonal antibodies (Mabs), B4 and HUC 1-1, known to be muscle actin selective. As a control, we also examined the immunoreactivity of a third Mab, C4, that reacts with all non-muscle and muscle vertebrate isoactins. Using light and electron microscopy, a progressive increase in immunolabeling was observed with the muscle selective HUC 1-1 Mab over a loose actin filamentous network distributed throughout the cytoplasm of steps 4-16 spermatids. Thereafter, the labeling decreased such that at step 17 spermatids, only cytoplasmic labeling in the tail of the spermatids was observed. No labeling of this network was noted with the C4 or B4 Mabs. However, myoid cells enveloping seminiferous tubules and smooth muscle cells of interstitial blood vessels demonstrated comparable intense labeling with each of the three Mabs. The C4 Mab intensely labeled actin filaments of the Sertoli-Sertoli and Sertoli-spermatid ectoplasmic specializations. Also well labeled were numerous actin filaments found in the apical Sertoli cell processes encapsulating the heads of late step 19 spermatids at stage VII of the cycle of the seminiferous epithelium. In addition, actin filamentous bundles enveloping tubulobulbar complexes of the late spermatids within the Sertoli cell apical processes were intensely labeled. The actin filaments in the Sertoli apical processes and surrounding the tubulobulbar complexes were also strongly immunolabeled with the HUC 1-1 Mab. The C4 Mab but not the B4 or HUC 1-1 Mabs, recognized actin in the subacrosomal space of steps 4 18 spermatids. This study suggests that there are muscle isoforms of actin within the cytoplasm of developing spermatids and within apical processes of Sertoli cells. PMID- 1750713 TI - Cervical lymph nodes and mast cells in the marsupial Sminthopsis crassicaudata. AB - A study of the cervical lymph nodes from the fat-tailed dunnart, Smithopsis crassicaudata, revealed the nodes were pigmented with lipofuscin and contained many large cells which were identified as mast cells from their ultrastructure and histochemical staining properties. It is believed that the very high density of mast cells in the cervical lymph nodes contributed to an increase in size of these organs compared to other animals. Very high levels of histamine (90 micrograms/g) were found in the nodes. Cervical lymph nodes with these unusual features were found not only in healthy, umprimed laboratory bred adults, but also in pouch young, wild caught animals, and adults of the closely related species, Sminthopsis macroura. A comparison of the histochemical and ultrastructural characteristics of mast cells from various organs of adult S. crassicaudata was also made. Mast cells from lymph node, skin, tongue, salivary glands, intestinal mucosa, and spleen showed slight variations in staining and structure. PMID- 1750714 TI - Evidence that vinculin is co-distributed with actin bundles in ectoplasmic ("junctional") specializations of mammalian Sertoli cells. AB - Ectoplasmic specializations of Sertoli cells are actin containing structures found at sites of attachment to spermatids and to neighboring Sertoli cells. We suspect that these cytoskeletal structures are a form of actin-associated adhesion junction. If this is true, then molecular components, such as vinculin, that characterize actin-associated adhesion junctions in general should be present in ectoplasmic specializations. In this paper we have used two approaches to verify the prediction that vinculin is a component of ectoplasmic specializations. First, we have used fluorescence microscopy to probe immunologically for vinculin in ectoplasmic specializations associated with spermatids of the ground squirrel. Second, we have used immunogold techniques to probe for vinculin in ectoplasmic specializations of rat testis. Our results indicate that the immunological probe for vinculin was reactive with ectoplasmic specializations. In single label fluorescence experiments, linear patterns obtained with the vinculin probe were similar to those obtained with probes for filamentous actin. In double label experiments, the vinculin probe was co distributed with the actin probes. In immunogold studies, specific labelling with the probe for vinculin occurred in ectoplasmic specializations both at sites of attachment to spermatids and adjacent to basal Sertoli cell junctions. Moreover, gold particles were concentrated adjacent to filament bundles within each ectoplasmic specialization. Our results support the conclusion that vinculin is present in ectoplasmic specializations. Further, they indicate that vinculin is co-distributed with actin bundles within each ectoplasmic specialization. PMID- 1750715 TI - Patch tests: will they die a bureaucratic death? PMID- 1750716 TI - Licensing of allergen patch tests. PMID- 1750717 TI - Recent advances in contact dermatitis. PMID- 1750718 TI - Skin test reactivity to whole body and fecal extracts of American (Periplaneta americana) and German (Blatella germanica) cockroaches in atopic asthmatics. AB - Forty-six atopic asthmatic subjects aged 3 to 58 years attending the allergy clinic of a university hospital were evaluated for prick skin test reactivity with commercially available extracts of cockroach (CCE) and house dust (HD). Additionally, skin testing was performed with American cockroach whole body (AWBE) and fecal extracts (AFE) as well as German cockroach whole body (GWBE) and fecal extracts (GFE) prepared in our laboratory. Commercial cockroach extract was prepared from American, German, and Oriental cockroach whole bodies. Skin test reactivity to the different extracts were as follows: 83% to HD, 70% to CCE, 70% to AWBE and/or GWBE, 63% to AWBE, 57% to GWBE, 63% to AFE and/or GFE, 52% to AFE, 50% to GFE, 48% to both AWBE and GWBE, and 39% to both AFE and GFE. The subjects with positive skin tests to AWBE and/or GWBE (70%) were the same individuals who showed skin test reactivity to CCE (70%). Subjects from lower income families (less than $10,000) had a significantly higher skin test reactivity to cockroach allergens than those from families with an annual income of $11,000 to $24,000 (P = .04). These results demonstrate the significance of cockroach sensitization in atopic asthmatics, suggest the importance of fecal cockroach allergens, and support earlier observations of shared interspecies allergens between American and German cockroach whole bodies. PMID- 1750719 TI - Outcome of habit cough in children treated with a brief session of suggestion therapy. AB - Nine patients with habit cough, initially misdiagnosed as asthma, were treated during a period of sustained repetitive symptoms with a brief session of suggestion therapy. Symptoms had previously been present for up to 2 years (median = 2 months). Five had been hospitalized for the cough. Evaluation revealed no physiologic or radiologic abnormality. All patients became symptom free during a 15-minute session of suggestion therapy. During the subsequent week, one remained completely asymptomatic and 8 had transient minor relapses that were readily self-controlled. Seven of the 9 could be contacted for determination of long-term outcome at periods up to 9 years (median 2.2 years) after the session. Six were totally asymptomatic; one had occasional minor self controlled symptoms. A standardized questionnaire assessing psychologic symptoms at the time of follow-up revealed no somatization nor emotional distress. In contrast to this apparent cure, others have reported extended periods of continued symptoms in the absence of a uniform treatment plan for suggestion therapy even though the correct diagnosis was made. We conclude that the classical habit cough syndrome is amenable to immediate relief and long-term cure in most cases with a single session of appropriate suggestion therapy. PMID- 1750720 TI - Repeated dosing of Uniphyl tablets under fed and fasting conditions: comparison of serum theophylline levels, pulmonary function, and asthma symptoms. AB - In order to determine the effects of repeated administration under fed and fasting conditions on the bioavailability and clinical efficacy of Uniphyl tablets, 22 adult asthmatics took the drug immediately following their evening meal for seven consecutive days and under fasting conditions for an additional seven consecutive days. For each patient, the daily theophylline dose remained constant throughout the study. Peak and trough serum theophylline concentrations (STC), spirometry, asthma symptoms, side effects and use of beta-agonist inhalers were recorded daily at 0730 and 1900 hours. The mean daily theophylline dose was 818.2 +/- 213.0 mg. The mean peak STC when Uniphyl was taken with food was 14.4 +/- 4.5 mg/L and was 13.1 +/- 3.6 mg/L when taken under fasting conditions (P less than .05). The trough STC was 7.4 +/- 2.8 mg/L with food and 6.9 +/- 2.1 mg/L while fasting (NS). There were no significant differences between the two dosing conditions in terms of spirometry, asthma symptom scores, side effects or use of beta-agonist inhalers. There was no significant difference between the patients' morning and evening FEV1 under either dosing condition. Since the differences in STC between fed and fasting conditions were not clinically significant, we conclude that there is no need to restrict patients to a rigid relationship between Uniphyl dosing and meal conditions. On the basis of patient preference and compatibility with a normal lifestyle, we recommend that patients should generally be instructed to take the drug with or shortly following their evening meal. PMID- 1750721 TI - Intranasal treatment with lysine acetylsalicylate in patients with nasal polyposis. AB - Forty-three patients suffering from nasal polyposis underwent intranasal treatment with increasing doses of lysine acetylsalicylate (LAS) corresponding to 20, 200, and 2000 micrograms of aspirin (ASA), until a maximal dose of 2000 micrograms weekly was reached. The patients were divided in two groups: a group of 28 patients with ASA intolerance, including 20 with ASA triad, and a group of 15 patients without ASA intolerance. The local treatment was usually started 1 month after polypectomy and was well tolerated without side effects. A control group included 191 subjects with nasal polyposis, 130 of whom had ASA intolerance. After polypectomy the controls received no further medical treatment. Patients were examined every 3 months and radiographs of the paranasal sinuses were obtained every 6 months. After 24 months 34 of 43 patients (79.1%) treated with topical LAS had suffered no relapse of polyposis. Only 45 of 191 control patients (23.6%) failed to relapse after 24 months (P less than .0001). Nine of 28 (32.1%) ASA-intolerant patients treated with LAS and 105 of the 130 (80.77%) control subjects relapsed (P less than .0001). None of the 15 ASA tolerant patients treated with LAS relapsed, but 41 of the 61 (67.21%) nontreated control subjects relapsed (P less than .00001). These data indicate topical LAS is effective in preventing recurrence of nasal polyps after polypectomy. PMID- 1750722 TI - Evaluation of oral terfenadine for treatment of the common cold. AB - This study was a single center trial comparing the effects of the nonsedating antihistamine terfenadine, at a dose of 120 mg twice a day, with placebo in the treatment of rhinitis symptoms associated with the common cold. Forty-nine subjects were treated with terfenadine, 120 mg twice each day, and 48 subjects were treated with placebo twice each day for four or five days. Evaluations by both subjects and physicians suggest that terfenadine at 120 mg given twice daily marginally improved sneezing and total symptom scores at day 4. When comparing terfenadine to placebo, neither the symptoms nor signs of the common cold improved in a clinically or statistically significant manner. Terfenadine was well tolerated and had a low incidence of side effects. Terfenadine was found to be ineffective in the treatment of the signs and symptoms of the common cold. PMID- 1750723 TI - Etiologic significance of mosquito (Anopheles stephensi) in respiratory allergy in India. AB - The etiologic significance of Anopheles stephensi, a common mosquito species in Delhi, in respiratory allergic disorders was investigated. Intradermal (ID) tests with the mosquito whole body extract (WBE) were performed on 247 patients with bronchial asthma and/or rhinitis and 50 healthy nonallergic volunteers. Of these 247 patients, 118 (47.8%) had positive (1+ to 4+) reactions including 72 (29.1%) with markedly positive (2+ to 4+) ID reactions. We did not observe any 2+ to 4+ skin reactions in normal healthy volunteers, giving evidence for the specificity of markedly positive ID response. The skin test positivity was not influenced by various clinical characteristics (age at onset, duration and type of disease, and family history) of patients included in the study. The specificity of positive ID response was further supported by the results of mosquito RAST with the sera of 14 patients. Ten of the 12 sera (83%) from patients with positive ID response to mosquito WBE were RAST positive. Sera from two patients with negative ID reactions were RAST negative. The bronchial provocation tests (BPTs) were uniformly negative in all five healthy volunteers and two patients showing negative ID responses to mosquito WBE, while the three patients showing 2+ to 4+ responses gave positive BPTs. Our results suggest that mosquito-derived particles are important inhalant allergens in the etiology of IgE-mediated respiratory allergic disorders in India. PMID- 1750724 TI - Consistency of evaluators assessing inhaler technique. AB - Since correct inhaler technique is vital for maximum efficacy, the evaluation of technique in patients or health care professionals involved in education programs or research projects is essential. Inconsistency could lead to confused patients and inaccurate research findings. This study is the first to determine interrater consistency with assessing recitation and demonstration of inhaler technique and, if needed, was designed to improve consistency until 95% agreement was achieved. A checklist for correct inhaler technique was constructed by consolidating information from the literature and package inserts. Initially three evaluators were used, however, a fourth evaluator was added for the last two trials to create teams to improve consistency. Percent agreement, probability and kappa scores were calculated. Six trials evaluating inhaler technique of 56 health care professionals at five different sites, revisions of the checklist, and evaluator teams were required to increase overall percent agreement from 81% to 98%. Agreement increased substantially on the verbal component because of specific changes made in the checklist and the objective nature. Demonstration steps consistently had lower agreement than verbal steps. Agreement on the demonstration component was more difficult because of subjectivity involved in observing a subject actuate the inhaler at the correct time, inhale or exhale slowly, and hold one's breath. The relative rankings of percent agreement and kappa scores were the same, however, kappa scores allowed differentiation of agreement due to chance and ability. To achieve interrater consistency, training and practice are required. Interrater consistency should be achieved to ensure accurate reporting of research results on inhaler technique and education of patients. PMID- 1750725 TI - Association of cigarette smoking with elevated serum IgE levels in Hispanic Puerto Rican men. AB - Unexplained elevation of serum IgE concentrations occurs in cigarette-smoking Caucasian males from temperate zones. To determine whether race or geography might be factors, we measured serum IgE concentrations in 94 Puerto Rican Hispanic patients, including smokers and nonsmokers. Mean serum IgE levels were elevated in our total patient population compared with Caucasian Americans. Geometric mean IgE was significantly increased in total smokers (157 IU/mL) compared with nonsmokers (78 IU/mL) and in male smokers greater than age 55 years (335 IU/mL) compared with male nonsmokers (41 IU/mL). Serum IgE was not significantly increased in female smokers. Among patients older than 55 years, persistent elevation of serum IgE occurred in male smokers. Our findings in a Puerto Rican Hispanic population are similar to those in studies of Caucasian smokers in temperate zones. PMID- 1750726 TI - Interleukin 4-mediated induction of CD4+/CD8+ T cells during infancy. AB - Neonatal human CD4+ T cells will co-express CD8 on their surface following short term culture with interleukin 4 (IL-4). Adult T cells do not respond in this manner. In this study we examine this phenomenon as a function of age and determine that IL-4 responsiveness decreases with time to approach adult levels at about 2 years. This phenomenon may be relevant to the documented ability of neonatal CD4+ T cells to function as suppressors. PMID- 1750727 TI - Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge. AB - Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses. PMID- 1750728 TI - Scale model studies of the transport of airborne pollutants on coalfaces. AB - Studies have been carried out to investigate airflows in coalmine models, with special regard to the transport of airborne pollutants, and to examine how they relate to what happens at full-scale in an actual underground mine. If such models can be shown to provide data representative of actual mine ventilation engineering, then they can provide cost-effective alternatives to full-scale investigations. The work set out in the first instance to identify the properties of: (a) the bulk airflow and associated transport of airborne pollutants along a longwall coalface; and (b) the transport of material out of regions that were partially enclosed or poorly ventilated (e.g. in the cutting zone, in headings). For the former, an appropriate quantity is the dispersivity of the coalface airflow, for the latter the mean retention time. Both quantities may be rendered non-dimensional with respect to dimensions characteristic of the system and to velocities of the airflow. Their behaviour in relation to a third dimensionless quantity, the flow Reynolds' number is also important. Experiments were performed, using smoke or dust tracers, to investigate how these properties are interrelated and how they scale between small-scale and full-scale systems. They were carried out in a 1/10-scale laboratory model, in a full-scale surface model, and underground in an actual coalmine. The basis of most of the experiments was the 'tracer decay' method, in which the transport properties of the aerodynamic system under investigation were determined from observations of the changes in tracer concentration with time immediately following the removal of the tracer source. During these experiments, the feasibility of using small-scale models to investigate ventilation problems was clearly indicated and preliminary scaling relationships which may be used as an initial basis for predicting the transport and local build-up of pollutants in mines were developed. It is expected that applications of the ideas and methodology described will be relevant to other industries. PMID- 1750729 TI - Inhalation anaesthetics--exposure and control during veterinary surgery. AB - Results are reported for air sampling surveys carried out by the Health and Safety Executive (HSE) in 14 veterinary surgeries. For all personnel the geometric mean (GM) time-weighted average (TWA) exposures to halothane and nitrous oxide over the working period were 2.6 ppm (range: less than 0.5 119 ppm) and 100 ppm (range: 14-1700 ppm), respectively. Since surgery rarely lasted for more than 4 h the corresponding GMs for 8-h TWAs were lower, being 1.3 ppm (range: less than 0.5-34 ppm) for halothane and 34 ppm (range: 5-530 ppm) for nitrous oxide. The GM exposures of veterinarians and nurses were very similar. The size of the practice and the use of scavenging were significant factors in determining personal exposures to inhalation anaesthetics: by comparison general ventilation had little effect. The results are compared with earlier data from human surgery, and previous studies of exposure to inhalation anaesthetics during veterinary surgery are briefly reviewed. PMID- 1750730 TI - Inflammatory response to particles in the rat lung: secretion of acid and neutral proteinases by bronchoalveolar leucocytes. AB - Leucocyte proteinases are considered to be central to the tissue damage that is associated with chronic inflammatory lung disease. Both acid and neutral proteinases have the ability to degrade connective tissue molecules and both may therefore play a part in tissue proteolysis in inflamed lungs. In this study we have used a rat model of lung inflammation to investigate levels of acid and neutral proteinase activity in the bronchoalveolar region of control and inflamed lungs. We assessed the ability of proteinases, secreted by resident and inflammatory bronchoalveolar leucocytes, to damage the connective tissue molecule fibronectin. Inflammatory bronchoalveolar leucocytes had greater ability to mediate connective tissue damage than had resident alveolar macrophages and the tissue proteolysis was mediated, in the main, by proteinases active at neutral rather than at acid pH. The increased secretion of proteinase by inflammatory leucocytes was dependent on in vivo stimulation: exposing resident or inflammatory bronchoalveolar leucocytes in vitro to particulate or soluble stimuli had no effect in increasing their ability to degrade fibronectin or secrete the inflammogenic proteinase, plasminogen activator. Thus, neutrophils in the bronchoalveolar region of the rat lung have proteolytic activity which is mediated largely by neutral proteinases. PMID- 1750731 TI - Levels of exposure to wood dust. AB - Surveys of exposure to inhalable dust have been carried out in two woodworking machine shops and five other woodworking shops where both manual and machine tool work is carried out. The Occupational Exposure Limits for wood dust were found to be frequently exceeded in some workshops. It is possible that the fraction of dust projected from woodworking machines towards the operator may have contributed both to measured dust concentrations and to exposure. Dust exposure may be reduced by careful attention to enclosure and ventilation, possibly using total enclosure at some machines. Emission of dust from portable orbital type sanding machines was considerably reduced by the use of low-volume high-velocity type extraction. It is suggested that suppliers of woodworking machines should provide data on dust emission to assist the user to manage better the introduction of new machines. PMID- 1750732 TI - An estimate of the rate at which crocidolite asbestos fibres are cleared from the lung. AB - The cumulative fibre exposure of 36 deceased persons who had been employed on crocidolite asbestos mines of the NW Cape was compared with their lung burden determined by fibre count by optical microscope. Allowance for the period which lapsed between date of last exposure and death revealed a lung clearance rate amounting to a half-life of about 6 years. PMID- 1750733 TI - Ocular findings associated with congenital X-linked ichthyosis. AB - Ichthyosis is frequently associated with ocular and extraocular signs. We present a case of X-linked ichthyosis associated with alterations of the anterior and posterior segments. A penetrating keratoplasty was done, and because of the patient's corneal alterations, we did a histopathologic study of the button by light and transmission electron microscopy. PMID- 1750734 TI - Severe allergic keratoconjunctivitis and erythema multiforme after a routine eye examination: discerning the cause. AB - Acute allergic dermatitis of the eyelids with keratoconjunctivitis is associated with a specific triggering factor. Therapy for the acute inflammation can complicate the search for such a factor if the process worsens. We report a case of acute contact dermatitis and keratoconjunctivitis after a routine eye examination to demonstrate the difficulty in evaluating such patients and the role of skin patch testing in determining the cause. PMID- 1750735 TI - Pigmented paravenous retinochoroidal atrophy in a 68-year-old man. AB - A 68-year-old man with patchy paravenous zones of retinal degeneration with bone spicule pigmentation OU was diagnosed as having pigmented paravenous retinochoroidal atrophy. We reviewed the literature and found 71 previously reported cases of this condition. Most of the affected individuals were young adults. By comparison, our patient was afflicted at a considerably older age. PMID- 1750736 TI - Ocular findings in cutaneous T-cell lymphoma. AB - Seventeen patients with cutaneous T-cell lymphoma undergoing an investigative treatment regimen using extracorporeal photochemotherapy underwent ophthalmologic examinations to investigate the ocular findings in this disease. The most frequent finding was seborrheic blepharoconjunctivitis, which was noted in 13 of 17 patients. Other common lid findings included cicatricial ectropion, meibomianitis, chalazia, and madarosis. Corneal and conjunctival disease was also increased in this group of patients. The syndrome of cutaneous T-cell lymphoma has recently been redefined, and a discussion of the revised concept of this disease is included. Previous studies used the old definition of this disease and were limited to the subgroups of mycosis fungoides and Sezary syndrome, which comprise only one third of the cutaneous T-cell lymphoma population. PMID- 1750737 TI - Treatment for herpes zoster ophthalmicus: stellate ganglion block as a treatment for acute pain and prevention of postherpetic neuralgia. PMID- 1750738 TI - Tear lysozyme levels in contact lens wearers. AB - Tear lysozyme levels in various types of asymptomatic contact lens wearers were compared with those in age- and sex-matched healthy control subjects. We used a radial immunodiffusion technique, and the lysozyme levels were in the normal range in controls and contact lens wearers. A comparison of the tear lysozyme levels of 27 contact lens wearers (mean, 1.05 +/- 0.45 g/L) with 22 control subjects (mean, 0.84 +/- 0.39 g/L) was statistically significant (P less than .05). The mean tear lysozyme levels of rigid (1.12 +/- 0.54 g/L, P less than .05) and high water-content (1.20 +/- 0.43 g/L, P less than .03) contact lens wearers were increased in comparison with the control group. The tear lysozyme difference was significant (P less than .03) between high and low water-content (0.82 +/- 0.20 g/L) contact lens users. Our study revealed that, although most of the contact lens wearers were asymptomatic and there was no pathologic sign of external ocular inflammation, a change in tear lysozymes was observed. Contact lens wear is irritating to the cornea and conjunctiva, and tear lysozyme physiology is disturbed most by high water-content contact lenses. PMID- 1750739 TI - Antibiotic responsive exophthalmos and lateral rectus paralysis. AB - Sinusitis is an unusual cause of exophthalmos in adults since the advent of antibiotics. Many periorbital complications of sinusitis have been described; however exophthalmos associated with apparent sixth cranial nerve palsy in the absence of ipsilateral sphenoidal sinusitis is a rare and, to our knowledge, unreported complication of sinusitis. We report such a case that was treated with oral antibiotics. We believe that sinusitis must always be considered in adults as a treatable cause of exophthalmos and various orbital complications from isolated lateral rectus paralysis to acute-onset, acquired Brown's syndrome. PMID- 1750740 TI - [The perinatal transmission of the hepatitis B virus in the Paris area]. AB - HBsAg was detected in 152 pregnant women among 6,605 (2.3%) screened in the prenatal clinics of four hospitals representative of the Paris metropolitan area. In 98% of cases, HBsAg positivity indicated chronic HBV carrier status. Among patients born out of continental France (47% of screened women, 79% of positive women) relative risk of chronic infection was 6 in Asians, 5.5 in Africans, and 4 in French women born in non-continental France. No significant difference in medical history was seen between HBsAg-positive and HBsAg-negative patients, in any of the birthplace groups. In women born out of continental France, number of children and crowding in the home were correlated with HBsAg-positivity; these correlations were not found in French women born in continental France. In non African, non-Asian women, screening on the basis of medical, social and familial criteria (simulated in this study) would not be effective. Routine screening for HBsAg in pregnancy is advocated. The cost of the prevention of each case of perinatally acquired chronic HBV infection by routine screening followed by prophylactic treatment of a risk neonates was estimated at 180,000 French Francs (35,000 dollars). This approach is the only means of preventing the long-term life-threatening complications of chronic HBV infection in the 600 neonates born each year in France to HBsAg-positive mothers. PMID- 1750741 TI - [Post-vaccinal hemi-convulsion hemiplegia syndrome]. AB - An 18-month-old infant developed hemiseizure-hemiplegia syndrome following a booster dose of vaccine against diphtheria, pertussis, tetanus, and poliomyelitis. Clinical, CT scan, and electroencephalographic findings during the two-and-a-half-year follow-up are described. The timing of events and data from the literature suggest that hemiseizure-hemiplegia syndrome is related to post immunization hyperthermia rather than to direct neurologic toxicity of the vaccine. PMID- 1750742 TI - [Cerebral artery ischemia and neonatal convulsions]. AB - A new case of neonatal seizures due to arterial ischemia is reported and the symptoms and prognosis of this condition are discussed. Arterial ischemia should be routinely considered in neonates who develop seizures a few days after an uneventful birth. Seizure recurrences exhibit unchanging features, in particular consistent focalization. The value of cerebral CT scan studies is underlined. Transfontanellar ultrasonography is not helpful in this condition. MRI may be especially informative for monitoring anatomical lesions over time and Doppler studies may be of value when performed at a very early stage. The outcome in the case reported herein and in previous reports is fairly favorable. PMID- 1750743 TI - [Cardiac involvement in mucopolysaccharidosis. Apropos of an echocardiographic study in 8 cases]. AB - Of all the storage diseases, mucopolysaccharidosis is the one whose cardiac manifestations are probably the least well known. Clinical and above all echocardiographic findings of heart involvement were studied in 8 patients with mucopolysaccharidosis, including four with Hunter disease. The paucity of clinical manifestations was in sharp contrast with the highly informative echocardiographic results. Valvular dystrophy, usually of the left side of the heart, was the most common anomaly, with five patients affected. Whereas some valvular lesions had no consequences, others led to stenosis or incompetence. Asymmetrical hypertrophy of the septum was found in one patient. No patient had evidence suggestive of vascular involvement, in particular of the coronary arteries. PMID- 1750744 TI - [Examination of the prepuce in 511 nursery school children. The role of retraction technics]. AB - The foreskin of 511 nursery school children was examined. Among the 500 unoperated children, 69.4% had a freely retractable foreskin. Adhesions were found in 28% of children and phimosis in 2.6% (total proportion of children with phimosis including the operated cases was 4.5%). A negative history for forcible retraction was found in 63.6% of children; among these subjects, 64% had a freely retractile foreskin and 31.1% had adhesions, which were usually extensive. Among children who had undergone forcible retraction, 77.5% had a freely retractile foreskin and 22% had adhesions, which were minor in most instances (p less than 0.001). The person who performed forcible retraction (the family physician in 54% of cases) and the age of the child at the time of forcible retraction were recorded. This retrospective study in a pediatric population of mean age 3 years 7 months provides data on the outcome after forcible retraction. Mean age at forcible retraction was 13 months in 36.4% of patients. Among the 500 unoperated children, 204 (40.8%) were spontaneously free of foreskin adhesions. PMID- 1750745 TI - [An analytic study of cases of childhood diabetes in a pediatric department in Tunis]. AB - Insulin-dependent diabetes mellitus is common in Tunisia. Eighty-six pediatric cases managed at the diabetes clinic of a department of pediatrics in Tunis from 1979 through 1989 were studied. Relevant clinical and biological findings were abstracted from case-records. Admissions of patients with diabetes mellitus accounted for approximately 0.44% of admissions to the pediatric ward during the study period. Mean age of patients was 7 years. Sex ratio was 0.89. Polyuria with polydipsia and ketoacidosis were the two most common presenting manifestations. Mean blood glucose level at diagnosis was 22.44 mmol/l. Rate of consanguinity was 48%. HLA typing studies demonstrated a high prevalence of DR3 and DR4 alleles and especially of simultaneous expression of both these alleles. Several factors are incriminated in the development of childhood insulin-dependent diabetes mellitus. PMID- 1750746 TI - [Value and limits of research on Mycoplasma hominis and Ureaplasma urealyticum in the gastric fluid of newborn infants]. AB - Mycoplasma hominis and Ureaplasma urealyticum were cultured and counted in the gastric fluid of 153 neonates divided into three groups: 28 preterm neonates managed in an intensive care unit (Group I); 83 full term neonates with suspected infection (Group II); and 42 full term neonates with no evidence of infection (Group III). The colonization rate (17.85%) in the intensive care unit group was not significantly different from the rates seen in the two other groups. These results do not militate against the pathogenic role of the two organisms studied but rather suggest a contributory role of other factors. PMID- 1750747 TI - [The efficacy of smectite in acute infantile diarrhea, compared to a placebo and loperamide]. AB - Fifty-six infants (aged 2 months to two years) with moderate to severe diarrhea were entered in a comparative therapeutic trial of smectite versus placebo or loperamide. Results showed that diarrhea resolved faster under smectite than under placebo and at least as fast under smectite as under loperamide. Tolerance of smectite is excellent as a result of the lack of any effect on intestinal motility. PMID- 1750748 TI - [Prevention of neonatal conjunctivitis. A comparative clinical and bacteriologic study of 2 eyedrops: silver nitrate and oxytetracycline chlorhydrate]. AB - This study carried out at the Saint-Germain-en-Laye Hospital maternity ward included all the neonates delivered between February and September 1989 who exhibited no abnormal manifestations during their stay in the ward, except for ocular symptoms in some subjects. Nine hundred neonates were enrolled. Each day, one of two eyedrop preparations for the prevention of neonatal ocular infections was selected at random. Investigators were blinded to the preparation used. Study subjects were evaluated twice, between D1 and D7 (900 infants) and between D15 and D30 (407 infants). Ocular findings were classified as follows: normal, minimally abnormal (isolated swelling of the eyelids, clear discharge), or frankly abnormal (conjunctivitis, purulent discharge). A bacteriologic study was performed in all patients with minimally abnormal or abnormal findings. Between D1 and D7, ocular symptoms were significantly (p less than 0.05) more prevalent in neonates treated with silver nitrate than in neonates treated with oxytetracycline hydrochloride. This difference was no longer present between D15 and D30. Bacteriologic studies recovered no gonococci. One enfant in the oxytetracycline group had bacteriologically confirmed Chlamydia trachomatis ocular infection. The other organisms recovered were mainly Staphylococcus aureus and non-hemolytic streptococci. In inclusion, no currently available eyedrop preparation offers complete protection against C. trachomatis but tolerance is considerably better with oxytetracycline hydrochlorate than with silver nitrate. PMID- 1750749 TI - [Post-vaccinal hemi-convulsion hemiplegia syndrome]. PMID- 1750750 TI - Measurement of growth variability and environmental quality in Guatemalan children. AB - The measurement of within-population growth variability may be a sensitive indicator of environmental quality. Specifically, it is hypothesized that within population variability will increase in adverse environments. To evaluate this hypothesis the variability in stature growth of three samples of Guatemala school children (5-10 years old) is assessed. These samples include high socioeconomic status (SES) ladinos (84 boys and 98 girls) and low SES ladinos (136 boys and 101 girls) living in Guatemala City and very low SES Mayan Indians (139 boys and 73 girls) living in a rural town near the city. SES is used as a proxy for environmental quality. The coefficient of variation (CV) for distance achieved at each age, or for the increment of growth from age to age, is used as the measure of variability. The three samples differ significantly for variability in stature growth, both for the distance and the increments of growth. Low SES urban ladinos have the largest variability. Very low SES Mayan children have coefficients of variation that are sometimes equal to, and sometimes either larger or smaller than, CVs for the high SES ladinos. The results show that degree of environmental adversity does not correlate uniformly with growth variability. Factors such as rates of infant and early childhood mortality and the greater heterogeneity of the low SES urban environment, compared with the high SES urban or low SES rural environments, may account for differences in the CV in these three samples. PMID- 1750751 TI - Population genetics of abnormal haemoglobins in Burkina Faso, west Africa. AB - The gene frequencies of haemoglobin A (HbA), HbS and HbC were studied in Burkina Faso (BF) and in a neighbouring region of Niger, Ayorou. The frequency of HbS was higher in the Sahel region, (northern part of BF and Ayorou) than in the Savanna region. The reverse was true for the HbC gene. The major findings of this study are: (a) confirmation of a peak of HbC gene frequency in the central region of BF (Mossi plateau); (b) a possible negative correlation between the frequencies of HbS and HbC-Cavalli-Sforza and Bodmer have observed that this correlation is at a significantly different level from that expected because of the allelic relationship between HbS and HbC; (c) comparison with the data collected by Livingstone shows a modification in the fitness of the different genotypes in the last thirty years: AS individuals have a lower and AA and SS a higher fitness. Our data favour a partial selection relaxation in this region. PMID- 1750752 TI - Tempo-unconditional 1-year bone score velocities in well-off north-west Indian children. AB - Tempo-unconditional 1-year bone maturity score velocities in well-off 6-16 year old North-west Indian children from Chandigarh (245 boys and 238 girls) are presented for the first time using the TW2 system. Rater's replicability/comparability was high. The peak RUS bone maturity score velocity is reached at 13 years in girls and at 15 years in boys, maintaining a standard 2 year difference. Velocities of the three bone maturity scores are relatively larger, but their respective standard deviations are smaller than those reported for American whites and blacks. North-west Indian children seem to be maturing faster than the British standards. PMID- 1750753 TI - Longitudinal analysis of incomplete adolescent data. AB - An approach is illustrated for the analysis of longitudinal variables collected during adolescence. Since the method requires complete data, three techniques are compared for application when some individuals have missing values. These methods are implemented in a study of systolic blood pressures and dietary fat intakes collected longitudinally in adolescent girls. The value of adolescent systolic and fat variables in predicting systolic pressure in adult women is investigated. PMID- 1750754 TI - Anthropometric-hormonal correlation patterns in San and Kavango males from Namibia. AB - Correlations between sex hormone levels and body dimensions--so far investigated only in Caucasian populations--were analysed using data from 114 !Kung San hunter gatherers and 137 urban and rural Kavango men from Namibia. The androgens testosterone (Tser) and 5 alpha-dihydrotestosterone (DHT) in the serum and free testosterone in the saliva (Tsal) as well as oestradiol (E2) in the serum were determined by the radioimmunoassay method. The body dimensions were described by 50 anthropometric features which were additionally subjected to factor analysis yielding seven factors. Most of the individual measurements as well as the resulting factor scores correlated significantly with the sex hormone variables and the hormone ratios Tser/DHT, Tsal/Tser, and Tser/E2 in the !Kung San and the two Kavango samples. For an extended comparison pertinent data from a German sample were included in the analysis. This made it possible to test the stability of metric hormonal correlations in different populations living under various ecological and economical conditions. While the breadth measurements in all samples show relatively consistent correlations to both absolute hormones and hormone ratios, the correlations to the other body measurements and individual factor scores turn out to be less stable. Here, the effect of sex hormones on physical growth, which is experimentally well documented, is obviously differentially covered by genetic and environmental factors specific for the groups in question. PMID- 1750755 TI - Physical growth of children treated for phenylketonuria. AB - The growth of 133 children participating in the Collaborative Study of Children Treated for Phenylketonuria (PKU) was compared to growth data from the National Center for Health Statistics (NCHS) to determine whether the growth patterns of the children with PKU were the same as those of unaffected children. Height and weight by age, and weight by height, were analysed for ages 2-10 years. Head circumference by age was analysed for ages 2-7 years. Median height by age of the PKU children was consistently near the 50th percentile of the NCHS growth curves for males and females. However, for both sexes, median weight by height and by age was between the 50th and 75th percentiles for children over 3 years old. Two sample t-tests showed mean weight was significantly different (p less than 0.05) between the PKU and NCHS groups at most ages for both sexes. Median head circumference for the PKU children tended to be smaller than NCHS standards; however, the maximum difference at any age was less than 0.5 cm. Polynomial growth curves fitted to the PKU and NCHS growth data showed that, on average, the PKU males and females weighed more than their unaffected counterparts, while height and head circumference for both groups were very close. Including median serum phenylalanine (phe) level (mg/dl) in the growth curves suggested that the weight differences between the PKU and NCHS groups are related to degree of diet adherence. Higher phe levels in the PKU group were associated with higher weight levels, more so for girls (p less than 0.001) than for boys (p = 0.08). No relationship was found between phe level and height or head circumference. We conclude that growth in children treated for PKU differs from national standards for weight by age and weight by height, but not for height by age. We speculate that diet adherence may be an important factor in determining which children have a tendency to become overweight. PMID- 1750756 TI - Cerebral blood flow velocity changes after rapid administration of surfactant. AB - A computer linked Doppler system was used to make continuous measurements of cerebral blood flow velocity (CBFV) from the middle cerebral artery, mean arterial blood pressure (MAP) from the umbilical artery, and heart rate before, during, and for 20 minutes after the endotracheal administration of 200 mg/kg of porcine surfactant in 10 preterm infants with respiratory distress syndrome. Within two minutes of surfactant administration, there was a median fall of 6 mm Hg (15%) fall in MAP and 36% in CBFV. There was a change in the Doppler spectra with almost complete loss of diastolic velocities. A rapid reduction in pulmonary vascular resistance with consequent left to right ductal shunting is one possible cause. These acute changes in MAP and CBFV after bolus surfactant administration may increase the risk of intraventricular haemorrhage. PMID- 1750757 TI - Hypocapnia and cerebral ischaemia in hypotensive newborn piglets. AB - This study tested the hypothesis that hypocapnia superimposed upon hypotension produces a further reduction in cerebral blood flow velocity (CBFV). In 12 newborn piglets, CBFV was measured continuously by Doppler ultrasound through an artificial fontanelle. Hypotension was induced by removing 30 ml/kg of blood. Increasing the ventilator rate reduced the average arterial carbon dioxide tension from 5.5 to 2.0 kPa. When mean arterial pressure (MAP) was held steady at 45 mm Hg or above, hypocapnia produced a substantial drop in CBFV but, in all the piglets with MAP below 38 mm Hg, hypocapnia failed to change CBFV by 10%. Hypocapnia produced an increase in lactate in sagittal sinus blood but cerebral venous hypoxanthine concentrations were not affected by hypocapnia. Hyperventilation (without haemorrhage) produced a significant drop in MAP, preventable by infusing colloid. Hypocapnia itself does not further reduce CBFV in the hypotensive piglet. However, the pressure effect of hyperventilation may significantly impair the cerebral circulation. PMID- 1750758 TI - Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity. AB - Blood flow velocity and pulsatility index were measured with Doppler ultrasound in the superior mesenteric artery, coeliac axis, and anterior cerebral artery in 18 very low birth weight, small for gestational age infants, and compared with findings from 18 weight matched, and 18 gestation matched, appropriate for gestational age controls. Mean velocity in the superior mesenteric artery was lower in the small for gestational age infants (15 cm/s) than in the gestation matched control group (20.4 cm/s). In those small for gestational age infants who had evidence of fetal hypoxia the mean velocity in the superior mesenteric artery was even lower (11.5 cm/s). There were no differences in velocity in the cerebral artery among the groups. Infants who were small for gestational age still had significantly lower superior mesenteric artery velocity than gestation matched controls at 1 week of age. The results suggest a specific reduction in visceral perfusion in infants who are small for gestational age and who have experienced fetal hypoxia, and this could predispose these infants to necrotising enterocolitis. PMID- 1750759 TI - Global and depth resolved phosphorus magnetic resonance spectroscopy to predict outcome after birth asphyxia. AB - Twelve normal and 32 asphyxiated neonates were studied using global and depth resolved phosphorus magnetic resonance spectroscopy (31PMRS). Eight of the asphyxiated group died or survived with major neurodevelopmental abnormalities. A global phosphocreatinine/inorganic phosphate (PCr/Pi) ratio below the range of values from normal infants predicted adverse outcome after asphyxia with a positive predictive value of 64%, sensitivity 88%, and specificity 83%. Corresponding values for global inorganic orthophosphate/adenosine triphosphate (Pi/ATP) ratios were positive predictive value 88%, sensitivity 96%, and specificity 88%. Spatially localised MRS data, obtained using phase modulated rotating frame imaging, showed cerebral energy metabolism to be more abnormal in deep than superficial regions after birth asphyxia. However, in this population of full term infants none of the regional metabolite concentrations were superior to global data for prediction of outcome. PMID- 1750760 TI - Otoacoustic emissions and auditory brainstem responses in the newborn. AB - The auditory function of 370 infants, drawn from both low and high risk groups, was tested before postnatal discharge using three tests: standard auditory brain stem responses (ABR), automated analysis of ABR, and automated analysis of evoked otoacoustic emissions (OAE). All infants failing any neonatal test had further audiological evaluation. Follow up information was also available on those who passed neonatal tests. Automated OAE testing of both ears was quickest (median 12.5 minutes) and least invasive (no scalp electrodes). Bilateral failure rates (and upper 95% confidence limits) with a stimulus 35-36 dB above normal hearing threshold level (nHL) were 3.0% (4.6) with automated OAE, 3.2% (5.1) with ABR, and 2.7% (4.4) with automated ABR. Automated OAE was the test most sensitive for subsequently confirmed hearing impairment. Sequential testing with automated OAE followed, in those failing this test, by automated ABR would have provided a screening test for substantial hearing impairment with a specificity greater than 99% in this population. Possible application as a universal screen is discussed. PMID- 1750761 TI - Neonatal at risk screening and the identification of deafness. AB - From a cohort of 10,686 live births, 322 (3%) were identified as being at risk of a hearing impairment defined as moderate, or worse. These neonates were screened by measurement of auditory brainstem responses. The neonatal at risk screening programme was effective in terms of both yield and cost. The mean age at which hearing aids were fitted was 6 months in the children identified by the neonatal screen. Such a programme is both practicable and useful in a district general hospital. The yield from the neonatal programme was, however, only 43% of the total number of deaf children eventually identified from the cohort. The need to identify more deaf children by a sensitive infant distraction test screening programme remains. PMID- 1750762 TI - Impact of sleep and movement on gastro-oesophageal reflux in healthy, newborn infants. AB - Seventy four normal, healthy newborn babies were studied to examine the relationship between gastro-oesophageal reflux, sleep state, and movement. Multichannel pen recordings were made to determine sleep state, movement, breathing, and reflux. The mean number of reflux episodes per hour was highest in wakefulness, followed by active and indeterminate sleep. In quiet sleep reflux rarely occurred. The mean duration of reflux episodes per hour was longest in active sleep followed by wakefulness, indeterminate and quiet sleep. There was a strong positive correlation between duration of reflux and movement time for wakefulness, active and indeterminate sleep. Movement preceded 88% of all reflux episodes. Physiological reflux occurs in most newborn infants but is clinically inapparent. The results suggest that state and movement are related to the incidence and duration of reflux. Sleep state is therefore an important variable in determining normal values for reflux in infancy since developmentally the amount of sleep time lessens but quiet sleep proportionally increases. PMID- 1750763 TI - Patient triggered ventilation using a flow triggered system. AB - The role of patient triggered ventilation (PTV) for the newborn was assessed using a new patient triggered ventilator, the Draeger Bablylog 8000, which incorporates significant improvements in both ventilator performance and the triggering system. Thirty three infants, median gestational age 30 weeks and postnatal age 2.5 days, were entered into the study to compare blood gases obtained during conventional and patient triggered ventilation. Oxygenation did not improve with PTV in the group overall but increased significantly (median change 7%) in infants greater than 28 weeks' gestation. Arterial carbon dioxide tension (PaCO2) decreased during PTV in the majority of infants (median reduction 7%), this was not related to the gestational or postnatal age, but was greatest in infants previously on a low conventional ventilation rate. Blood gases (both PaO2 and PaCO2) deteriorated in infants requiring the highest inspired oxygen concentration. We conclude that patient triggered ventilation is most useful in infants with mild respiratory distress. PMID- 1750764 TI - Cardiac anomalies complicating congenital contractural arachnodactyly. AB - A newborn boy with congenital contractural arachnodactyly (CCA) was found to have an atrial septal defect, ventricular septal defect, patent ductus arteriosus, and aortic arch anomalies. These resulted in congestive failure but subsequent progressive dilatation of both great arteries and development of aortic regurgitation were associated with eventual cardiorespiratory failure and death at 11.5 months. Others have noted that cardiac anomalies in CCA may be comparable with those of infantile Marfan's syndrome. Our case further extends the spectrum of cardiac abnormalities in CCA and substantiates that there is overlap with infantile Marfan's syndrome. This fact and our literature review suggest that early and complete cardiac assessment is necessary for appropriate management and evaluation of prognosis in any newborn infant with findings suggestive of either condition. PMID- 1750765 TI - Amniotic fluid N-acetyl-beta-D-glucosaminidase activity and renal abnormalities. AB - Amniotic fluid N-acetyl-beta-D-glucosaminidase (NAG) activity was measured in 21 normal pregnancies to determine reference values, and in 10 pregnancies with fetuses who had prenatally recognised renal and urinary tract malformations. The normal values obtained at 17-19 and 28-31 gestational weeks did not differ, and an activity of 105 units NAG/mmol creatinine was the upper limit of the normal range. Raised NAG activities were found in four fetuses with oligohydramnios and severe bilateral renal disease, and also in two infants with a normal amount of amniotic fluid, only unilateral renal lesions, and a normal renal function after birth. Three of four cases with normal NAG activities had malformations without kidney damage, but one baby with prune belly syndrome was subsequently found to have dysplastic kidneys and renal failure. Our preliminary results suggest that a high level of NAG activity in the amniotic fluid indicates unilateral or bilateral kidney damage but is not proof of intrauterine renal failure. PMID- 1750766 TI - Factors influencing plasma renin and renin substrate in premature infants. AB - Concentrations of plasma renin (PRC) and plasma renin substrate (PRS) were measured during the first week of life in 52 infants born at less than 37 weeks' gestation (mean (SEM) gestation 30 (0.4) weeks, mean (SEM) birth weight 1.35 (0.08) kg). Both PRC (median 35, interquartiles 16.3, 94.5 ng/ml/hour) and PRS (median 2.3, interquartiles 1.3, 5.0 micrograms/ml) were raised compared with adults. The proportional rise in PRC was much greater than that in PRS, suggesting that PRS may be rate limiting in the generation of angiotensin I. Log10 PRC was inversely proportional to gestational age and a high urinary sodium loss was associated with a significantly raised log10 PRC. In hypoxaemic infants, there was a strong correlation between log10 PRS and haemoglobin concentration; this is a new observation in human infants but consistent with data available from other species. PMID- 1750767 TI - Diamorphine infusion in the preterm neonate. AB - The effects of diamorphine were studied in 34 premature neonates who were given a loading dose of 50 micrograms/kg of diamorphine followed by a constant rate intravenous infusion of 15 micrograms/kg/hour. Small but significant falls were noted in blood pressure (at 30 minutes) and heart rate (at 30 minutes, six hours, and 12 hours) after administration of diamorphine, but these did not appear to cause any clinical deterioration and were thought to be related to the sedative effect of the drug. A significant fall in respiration rate at 30 and 60 minutes reflected the desired intention to encourage synchronisation of the infants' breathing with the ventilator. The mean (SD) plasma concentration of morphine measured during the infusion at steady state was 62.5 (22.8) ng/ml (range 20 to 98 ng/ml). The data suggest that this dosage regimen of diamorphine is safe. It results in plasma concentrations of morphine in the premature neonate which are comparable with those that are known to provide effective analgesia in the child and adult. PMID- 1750768 TI - Imaging of neonatal arterial thrombosis. AB - The case of a neonate who presented with symptoms of upper limb ischemia related to spontaneous multiple arterial and venous thromboses that were demonstrated by colour Doppler sonography and digital subtracted angiography is reported. The presentation of limb ischaemia at birth may be the warning sign of simultaneous cerebral infarction. PMID- 1750769 TI - Intermittent fetal tachycardia and fetal hydrops. AB - A case is reported where fetal hydrops was noted 10 days after an initial observation of intermittent fetal tachycardia at 31 weeks. A diagnosis of supraventricular tachycardia was made and a successful conversion to sinus rhythm was achieved with maternally administered flecainide, with subsequent resolution of the hydrops. The fetus required no further treatment in pregnancy or at follow up. The mother suffered no side effects of the treatment. PMID- 1750770 TI - Family implications of neonatal Gorlin's syndrome. AB - Two very preterm infants (born at 29 and 25 weeks, respectively) were found to have abnormal ribs. Though this was thought unimportant at the time, it was subsequently shown to indicate that some members of their families had a dominantly inherited risk of developing skin cancer and other serious problems. PMID- 1750771 TI - Gastroduodenal perforation in preterm babies treated with dexamethasone for bronchopulmonary dysplasia. AB - Three cases of gastroduodenal perforation and one case of ulceration and extreme thinning of the gastric wall occurred in preterm babies treated with dexamethasone for bronchopulmonary dysplasia. This complication of treatment with steroids has not to our knowledge previously been described in preterm infants. Urgent abdominal paracentesis was an essential part of the resuscitation in these cases, and this potentially serious side effect should be considered in all babies treated with steroids. PMID- 1750772 TI - Premature labour. PMID- 1750773 TI - Dr Nils Rosen (1706-1773): the father of paediatrics in Sweden. PMID- 1750774 TI - Beyond the walls. PMID- 1750775 TI - Psychobiology and psychiatric nursing: a philosophical matrix. AB - Over the past several years, conceptualizations of the mind have been challenged by a knowledge explosion in the psychobiological sciences. Such new knowledge continues to fuel a paradigm shift in psychiatry away from traditional psychodynamic models of the mind and toward ones balanced with a psychobiological dimension. The combination of psychodynamic and psychobiological fields of knowledge offers an opportunity for a holistic perspective on the human experience. Psychiatric nursing faces the challenge of integrating this new knowledge for the enrichment of its practice. To accomplish this complex task, issues need to be addressed in many areas critical to psychiatric nursing. Three areas are discussed in this article and include philosophy, communication of philosophy, and testing of philosophy. This article concludes with a discussion of some potential mechanisms to deal with the tensions generated by a paradigm shift in psychiatric nursing. PMID- 1750776 TI - A model of clinical judgment processes in psychiatric nursing. AB - This study addressed judgment processes in psychiatric nursing by analyzing reported use of clinical cues cited as being relevant in the process of making a nursing judgment. Using an exploratory, qualitative approach, data were collected by interviewing 15 subjects who provided 36 in-depth interviews upon completion of an intake interview. Comparative content analysis was used to determine the underlying structure in subject reports. A model depicting judgment processes is presented and discussed. Results suggest that although judgments were highly context-dependent, all subjects assessed data labeled as universals in the psychiatric nursing assessment: suicidality, depression, drug and alcohol use, and patient functional abilities. Similarities among subjects were noted in that presenting behaviors were most salient, a categorization process occurs within the judgment process, and patients are included in the judgment process. Finally, nursing judgments uncovered an action orientation rather than a labeling function. PMID- 1750777 TI - Adolescents' attitudes toward mental illness and perceived sources of their attitudes: an examination of pilot data. AB - This exploratory descriptive pilot study examined the attitudes of 89 Floridian adolescents toward mental illness and found significant differences according to gender and education about mental illness. Responses to social distance items showed that adolescents tended to be less accepting as they were proposed relationships that suggested greater intimacy with the mentally ill. The mass media, personal experience with someone who had a mental illness, and parents were perceived by the adolescents as the most important sources of their attitudes. The major implications for nursing practice with adolescents, and particularly in the school system, are discussed with suggested interventions. PMID- 1750778 TI - Correlates of disruptive behavior in cognitively impaired elderly nursing home residents. AB - Disruptive behavior, resulting in negative consequences for both residents and caregivers, occurs in a large proportion of the nursing home population. This review of literature surveys studies that describe disruptive behavior and the correlates of this behavior in the cognitively impaired elderly. In the studies reviewed, the average prevalence of reported disruptive behavior among a total of 5,650 subjects was 42.8%. Correlates most frequently linked with disruptive behavior include cognitive status, functional ability, age, and premorbid personality. Suggestions for future research are discussed. PMID- 1750779 TI - The effects of reminiscence on psychological measures of ego integrity in elderly nursing home residents. AB - The purpose of this study was to investigate the efficacy of a reminiscence group to increase ego integrity in elderly nursing home residents. Erickson's developmental theory and Butler's theory of reminiscence provided the theoretical framework for the study. It was hypothesized that reminiscing would increase life satisfaction, self-esteem, and decrease depression. Fifty-four nursing home residents were randomly assigned to a reminiscence group or a control group. No statistically significant relationship was found between reminiscing and life satisfaction, depression, or self-esteem; however, results indicated there was a positive socializing effect for those who participated in the group process. PMID- 1750780 TI - Current treatment approaches to obsessive-compulsive disorder. AB - The two most useful treatments in obsessive-compulsive disorder are pharmacotherapy with potent serotonin reuptake-blocking agents and behavioral techniques, such as exposure and response prevention. Based on the authors' cumulative clinical experience, it is suggested that patient education, cognitive therapy, and psychodynamic psychotherapy are helpful adjuncts during various treatment stages of obsessive-compulsive disorder. The patient's strengths and knowledge of the illness can be used by the nurse-therapist to determine the implementation and timing of these therapeutic measures. Specific behavioral and cognitive techniques that may be useful in treating specific symptoms of obsessive-compulsive disorder are highlighted. Suggestions for future nursing research are outlined. PMID- 1750781 TI - Lance: a gay recovering alcoholic misdiagnosed as HIV-positive. AB - Lance is a 29-year-old gay alcoholic who was misdiagnosed as human immunodeficiency virus (HIV)-positive. In reaction to the diagnosis, Lance subsequently engaged in a series of destructive behaviors towards himself and others. When he was told that his diagnosis was in error, Lance was able to break out of his self-destructive cycle. This article explores the symbolic interactionist concepts of definition of the situation and of stigma and provides nursing implications for caring for people with HIV infection and the acquired immune deficiency syndrome. PMID- 1750782 TI - Literature: a vehicle for emotional connection between clinician and client. AB - Nurses have used literature in a variety of ways to increase understanding of the problems and dilemmas of their patients. Literature can be used in psychotherapy when a patient either selects a literary work to discuss or writes his or her own work. Incorporation of literature into psychotherapy offers opportunities for discussion that yield important information about the patient as he or she explores conscious and unconscious issues. PMID- 1750783 TI - The future of our profession from the eyes of today. PMID- 1750784 TI - Vascular access thrombosis in epoetin alfa therapy. PMID- 1750785 TI - The development of the nephrology nursing certification program. AB - The certification examination for nephrology nurses was developed by the Nephrology Nursing Certification Board (NNCB) and the ANNA Certification Ad Hoc Committee with guidance from the National League for Nursing (NLN) Test Services. The development of a written examination is the continuing responsibility of the NNCB. This article provides a summary of the 3 years experience with the examination and focuses on the process of actual test construction: the organization, development, evaluation, and quality of test items. PMID- 1750786 TI - Self-administration of epoetin beta by peritoneal dialysis patients. AB - Recombinant human erythropoietin (epoetin) reverses the anemia of end stage renal disease. Benefits have been evaluated primarily in hemodialysis patients because of the ease of administration via existing intravenous access. Studies are under way to evaluate the feasibility of subcutaneous self-administration of epoetin in continuous ambulatory peritoneal dialysis (CAPD) patients. Preliminary study results, using the maintenance of target hemoglobin levels to measure success and a case study demonstrate the practicality of subcutaneous self-administration of epoetin in CAPD patients. PMID- 1750787 TI - "If I only knew:" a patient education program on advance directives. AB - This article describes a unique renal patient education program on advance directives. It explains why the program was developed, the components of the program and their use, and the effects of the program. It is argued that programs like this one are needed to provide patients with reliable information about advance directives in a sensitive, time efficient manner. PMID- 1750788 TI - The synthetic axillofemoral graft for hemodialysis access. AB - Patients who have exhausted all options for conventional dialysis access due to lack of available vessels may be candidates for placement of a synthetic axillofemoral vascular graft. The axillofemoral access is surgically constructed under general anesthesia. The synthetic graft is anastomosed, end to side, to the axillary artery, proximally, and distally to the common femoral vein. Surgical complications have been negligible and intravascular blood flow rates support efficient dialysis. A review of two cases demonstrates the positive outcomes and acceptability of this nonconventional approach for blood access in hemodialysis patients. PMID- 1750789 TI - A care plan for self-administration of epoetin alfa. AB - A care plan was developed to assist nephrology nurses managing the care of patients self-administering epoetin alfa. This is a generic care plan intended to serve as a basis for communication and should be adapted for appropriateness to individual facilities. PMID- 1750790 TI - Documentation related to Epogen administration. PMID- 1750791 TI - Case study: end stage liver failure patient managed with CAVH pretransplant. AB - The patient met 4 of the 5 expected outcomes. Effective therapy with CAVH was maintained in the ICU setting and in the operating room. The catheters functioned throughout the entire treatment without signs or symptoms of infection, bleeding, or thrombosis. She received hyperalimentation, filtration replacement fluid, and adequate fluid boluses to maintain volume status, nutritional requirements and vital signs. Cardiac vasopressor medications were required for a short period. The one problem that did occur was related to the anticoagulation therapy. The PTT was checked every 4 hours and the heparin drip was titrated to keep the PTT at 50 to 60 seconds. At one point, the PTT was 92 seconds but immediate measures were undertaken to reverse the condition. In the situation where a patient has an underlying coagulopathy and a potential source of bleeding, the nursing recommendation is that hourly bedside ACTs with every 4 hour PTTs should be performed as a routine part of the care. CRRT has been used successfully in critically ill unstable patients with multiorgan involvement. These therapies provide an avenue for collaboration between nursing professionals in nephrology and critical care. The focus of CRRT can now progress from the technical aspects of the procedures to patient centered nursing issues. PMID- 1750792 TI - Medication review: fluconazole. AB - Fluconazole is an antifungal agent available for the treatment of oropharyngeal and esophageal candida and cryptococcal meningitis. It has been found to be equal to or more efficacious than amphotericin B in treating oral and esophageal candidiasis and in providing maintenance therapy for cryptococcal meningitis. It still remains to be seen if it can be equally effective in treating acute cryptococcal infections and systemic candidiasis. In these fungal infections, amphotericin B remains the clinically proven drug of choice. To its advantage, it does not cause acute renal failure, bone marrow depression, or suppress corticosteroid production which are significant drawbacks to other available agents. It is a drug with great promise for its specific indications, but more studies in renal failure and organ transplant patients are needed to firmly establish its efficacy in these populations. PMID- 1750793 TI - Case management of the anemic patient. Epoetin alfa: focus on dialysis efficiency. AB - Dialysis efficiency has traditionally been measured using kinetic modeling (KT/Vurea). However, once anemia is corrected with Epoetin alfa, using urea as the only measure of dialysis effectiveness may not be adequate. Two case studies describe the use of the urea kinetic model and other means of assessing dialysis efficiency in nonanemic patients. PMID- 1750794 TI - Systemic sclerosis (scleroderma). Introduction. PMID- 1750795 TI - Raynaud's phenomenon: its relevance to scleroderma. PMID- 1750796 TI - Epidemiology of scleroderma. PMID- 1750797 TI - Clinical aspects of systemic sclerosis (scleroderma). PMID- 1750798 TI - Major histocompatibility complex class II genes and systemic sclerosis. AB - 1. In no ethnic group is the overall association between systemic sclerosis and the MHC strong enough for direct clinical use. MHC associations do support the classification of the disease into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 2. Indications are that associations between specific subsets of patients with systemic sclerosis and genetic markers will assume greater importance both diagnostically and prognostically. The group with lung fibrosis look prime candidates, for example. 3. Genetic markers are useful means of relating chemically induced systemic sclerosis like disorders with the classical disease. Vinyl chloride disease provides an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in systemic lupus erythematosus. We believe that, eventually, genetic tests will be used to influence treatment in at least a subset of patients with systemic sclerosis but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic--that is, the overproduction of collagen. In this respect it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the action of Scl-70 (topoisomerase I). A problem is how to tie this and the other observations discussed above together. The association of autoantibodies with topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl-70 in systemic sclerosis is unknown, humoral autoimmunity, at least in systemic lupus erythematosus, seems to be strongly dependent on specific HLA genes. With an understanding of the function of MHC products at the molecular level, HLA and disease associations can now be analysed on a mechanistic level. For insulin dependent diabetes mellitus it has been shown that the MHC determined susceptibility to the disease is conferred by neutral residues (Val, Ser, Ala), at position 57 of the DQ beta chain, while Asp at this position correlates with resistance. A similar phenomenon has been described in rheumatoid arthritis. Although DR4 in general is associated with rheumatoid arthritis, it is heterogeneous, but a subtype of DR4 which is characterised by positively charged residues at positions 70 and 71 of the beta chains is not found in patients with rheumatoid arthritis (Wordsworth B P et al, unpublished data). A similar approach applied to the study of systemic sclerosis is likely to be similarly rewarding. The precise subtyping of the class II genes and the characterisation of their associated haplotypes is therefore required for a complete understanding of the contribution of the MHC to the disease. Additional genes linked to the MHC must not be overlooked, and are relevant to associations of haplotypes with the disease. Of particular interest are the recent reports of a new class of proteins, which are determined by genes in the MHC and which are considered to play a part in the assembly of the antigen peptide/MHC molecule complex. PMID- 1750799 TI - The endothelium: its role in scleroderma. PMID- 1750800 TI - Transcriptional control mechanisms for the expression of type I collagen genes. PMID- 1750801 TI - Treatment of systemic sclerosis. AB - Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of subjects with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk of developing serious disease of the internal organs (intestine, lung, heart, kidney) and should be considered for disease modifying treatment. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotective agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new agents with sound scientific rationale are currently undergoing therapeutic trials. Much can be done to improve the lifestyle of those with scleroderma. The most dramatic recent development is the ability to reverse kidney disease by the prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease. PMID- 1750802 TI - The hyperlipidemic hamster as an atherosclerosis model. AB - The descending thoracic and abdominal aortas of normal and hypercholesterolemic Golden Syrian hamsters were examined with transmission electron microscopy and immunofluorescence microscopy. Serum cholesterol distribution in lipoproteins was determined by gradient ultracentrifugation. Luminal surfaces appeared free of lesions and no intimal thickening or foam cells were seen. The main rise of cholesterol during the hypercholesterolemic diet was in the VLDL + IDL fraction. These findings suggest differences in the localization of atherosclerotic lesions and lipoprotein cholesterol distribution between humans and hamsters, which hamper the use of this species as a model for human atherosclerosis. PMID- 1750803 TI - Effects of long term 2% fish oil supplements on tissue fatty acids, phospholipids, cholesterol, and arterial histology in Japanese quail (Coturnix coturnix japonica). AB - The effects of 2% olive oil (OO) or fish oil (FO) (Super epa500) dietary supplementation (9 months) on Japanese "SEA" quail was investigated. The animals were examined for tissue biochemical changes and possible blood vessel fatty deposition. The fatty acids of blood and tissue extracts from heart, liver and fat were analyzed by gas-chromatography/mass spectrometry. The ratio of arachidonic acid to eicosapentaenoic or docosahexaenoic acid was markedly decreased in FO treated animals compared to OO or control diet treated animals. Tissue cholesterol and total phospholipids were present in elevated amounts in the heart and liver of FO treated animals. After the 9-month regimen many animals had residual atherosclerotic lesions but the FO treated birds had considerably more fatty streaks and fatty deposition in their large vessels compared to control or OO treated animals. Although the lipid composition of tissues of FO treated animals would indicate that the purported cardioprotective omega-3 fatty acids are enriched in the various tissues examined compared to olive oil and control diet treated animals, the possible detrimental effect of saturated fat, cholesterol, or some other component of the fish oil preparations is suggested from the histological appearance of fatty deposition in the blood vessels (aortae) of these inbred animals. These results in quail are strikingly similar to that seen in the omega-3 FA treated WHHL rabbit (15). PMID- 1750804 TI - The effect of apolipoprotein E isoform difference on postprandial lipoprotein in patients matched for triglycerides, LDL-cholesterol, and HDL-cholesterol. AB - The postprandial response to three test meals provided during a single day was investigated in subjects with either the apo E3/3 phenotype (n = 8), or the apo E4/3 phenotype (n = 4), who had LDL-C greater than 160 mg/dl. Vitamin A (60,000 U/m2) was ingested with the first meal and retinyl palmitate determined four hours later. Triglyceride and total cholesterol concentration were determined on whole plasma and total cholesterol and free cholesterol determined following single spin ultracentrifugation (d less than 1.006 g/ml) and dextran precipitation of the d greater than 1.006 fraction to separate apoprotein-B containing lipoproteins. Fasting values revealed significantly lower HDL cholesterol ester (p less than 0.03) and HDL3-cholesterol ester (p less than 0.03) and significantly greater HDL-free cholesterol (p less than 0.03) and HDL3 free cholesterol (p less than 0.02) in subjects with the E4/3 phenotype. Four hour postprandial HDL and HDL3 cholesterol ester increased significantly more (p less than 0.05) in E4/3 patients and HDL and HDL3 free cholesterol decreased significantly more (p less than 0.05) in E4/3 subjects. Eight-hour postprandial change values maintained the significant HDL3-cholesterol ester and free cholesterol difference, and, revealed a significantly greater triglyceride rich lipoprotein cholesterol ester reduction (p less than 0.01) in the E4/3 group. Individuals with the apolipoprotein E4/3 phenotype reveal significant differences in postprandial lipemia compared to individuals with the E3/3 phenotype, and, postprandial lipemia following multiple meals reveals differences not apparent from responses to a single meal. PMID- 1750805 TI - Lecithin:cholesterol acyltransferase activity in patients with acute myocardial infarction and coronary heart disease. AB - Literature data suggest that identification of the conditions preventing lecithin:cholesterol acyltransferase (LCAT) to produce normal cholesterol esterification might be of utmost importance in the follow-up of atherosclerosis. Interrelationship between LCAT activity, and total cholesterol (TC), unesterified cholesterol (UC), esterified cholesterol (EC), low and high density lipoprotein cholesterol (LDL-C, HDL-C), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), l-lactate (LAC), and electrolytes, i.e. zinc (Zn), calcium (Ca) and magnesium (Mg), was investigated in 60 patients with acute myocardial infarction (AMI), 30 patients with coronary heart disease (CHD) and 30 healthy control subjects. Results of the study revealed LCAT activity to be significantly decreased in atherosclerotic patients, with a significantly increased ratio of unesterified-esterified cholesterol (UC/EC), as compared to the control group of normal subjects. A decreased LCAT activity was accompanied by elevated values of phospholipids and LDL-C, a moderate increase in triglycerides, and a decreased quotient of HDL3/HDL2 cholesterol. Accordingly, a decreased activity of LCAT could with great certainty be considered a high-risk biochemical factor for atherosclerosis. PMID- 1750806 TI - Guidelines for the nursing management of alcohol related withdrawal symptoms in the home. PMID- 1750807 TI - Recreation in a nursing home: a nursing success. PMID- 1750808 TI - Postnatal depression: increasing professional and community awareness. PMID- 1750809 TI - ANF, HIV/AIDS train the trainer project year one completed. PMID- 1750810 TI - Cisapride. PMID- 1750811 TI - Nurse and the law. In the best interests of the child. PMID- 1750812 TI - Aussie DRGs: development of the Australian Inpatient Casemix Classification. PMID- 1750813 TI - Surgery for asymptomatic primary hyperparathyroidism. PMID- 1750814 TI - Advanced trauma life support in the 1980s: a decade of improvement in trauma care. PMID- 1750815 TI - Ectopia and agenesis of the gall-bladder: a report of two sets of twins and review of the literature. AB - We report two sets of twins with agenesis and ectopia of the gall-bladder. It is important to be aware of this condition, as many of these patients present with biliary-type pain and have unnecessary laparotomies. The literature on this condition is reviewed. PMID- 1750816 TI - Ulcerative colitis in the anal canal of patients undergoing restorative proctocolectomy. AB - The development of stapling instruments has obviated the need to perform anal mucosectomy for ulcerative colitis, but the potential exists for continued inflammation and, perhaps, malignant change. We reviewed the pathology specimens of patients who had had restorative proctocolectomy, to determine the incidence and severity of inflammation in the anal mucosa. PMID- 1750817 TI - Anorectal physiology and pathology. PMID- 1750818 TI - Traumatic rupture of the thoracic aorta: ten-year experience with follow up. AB - In the past 10 years, 13 cases of acute traumatic rupture of the thoracic aorta were treated at the Dunedin Hospital. Ages ranged from 16 to 77 years, with a mean of 27 years. Twelve of the patients were involved in high speed motor vehicle accidents and one sustained a fall. The diagnosis was suspected in all 13 cases by a widened mediastinum on plain chest X-ray and confirmed by aortography in all cases. Associated injuries were common. The time interval from injury to surgery ranged from 5 h to 16 days, with a mean of 3 days. A Gott Shunt was used in five patients, seven had partial bypass and one had simple aortic cross clamping. Mean aortic cross-clamp time was 62 min. Mortality was 15%, both deaths occurring in the bypass group. There were two cases of paraplegia, one occurring in the bypass group and the other in the patient having simple cross-clamping of the aorta. Follow up was possible in 8 of 13 patients and ranged from 3 months to 10 years, with a mean of 39 months. Delayed death due to heart failure occurred after discharge in a 77 year old man 40 days after operation. The long-term results were satisfactory in all survivors, apart from one poorly rehabilitated paraplegic. PMID- 1750819 TI - Measurement of the healing of venous ulcers. AB - The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments. PMID- 1750820 TI - Inhibition of human endothelial prostacyclin synthesis by different aspirin formulations. AB - The availability of different formulations of low-dose aspirin for use as anti thrombotic agents merits a comparison of their effects on vessel wall biochemistry. We compared the effect of ingestion of an enteric-coated slow release aspirin (Astrix) with that of soluble aspirin (Cardiprin) on human endothelial prostacyclin synthesis. Patients undergoing varicose vein surgery (10 per group) ingested 100 mg aspirin per day as Astrix or Cardiprin for 7 days prior to surgery. A control group ingested no aspirin. Prostacyclin synthesis by the endothelial surface of the great saphenous vein was determined in vitro. Both aspirin formulations caused significant inhibition of endothelial prostacyclin synthesis compared with the control group. Using the median values, the enteric coated slow-release aspirin caused 76% inhibition, whereas the soluble formulation caused significantly greater inhibition (95%). If differential inhibition of platelet thromboxane synthesis with 'sparing' of endothelial prostacyclin synthesis is necessary for an optimum anti-thrombotic effect of aspirin, the results suggest that a lower dose of soluble aspirin than enteric coated slow-release aspirin may be preferred. PMID- 1750821 TI - Leiomyosarcoma of the superficial femoral artery presenting as a ruptured aneurysm. PMID- 1750822 TI - Pyogenic psoas abscess. AB - In a 12-month period, five cases of pyogenic psoas abscess presented to the Townsville General Hospital. These cases are presented, together with a review of the literature to illustrate the clinical features of this condition and the therapeutic challenge it may pose. PMID- 1750823 TI - Caecal volvulus in a child: an unusual postoperative complication. AB - A 2.5 year old dysmorphic child with severe gastro-oesophageal reflux was admitted for elective fundoplication. Three days postoperatively, she developed progressive signs of intestinal obstruction. The diagnosis of caecal volvulus was suggested on the plain radiographic appearance, confirmed at laparotomy and treated by right hemicolectomy. The predisposing factors, diagnosis and approach to surgical management are discussed. PMID- 1750824 TI - Rapidly growing twelfth rib osteoid osteoma. PMID- 1750825 TI - Adenocarcinoma in a female urethral diverticulum. AB - Carcinoma occurring within a diverticulum of the female urethra is an exceedingly rare disease for which the treatment is ill-defined. We present here the first reported case of this condition from Australasia and review some of the recommendations for treatment. PMID- 1750826 TI - Electromagnetic pulsed-wave radiation in spherical models of dispersive biological substances. AB - In analytical studies, we investigated induced-field patterns and SAR distributions in a lossy, dispersive, homogeneous, dielectric sphere typical of muscle tissue as irradiated by a plane-wave pulse train consisting of a pulse modulated sinusoidal carrier wave. Calculations were made for carrier frequencies of 1, 3, and 15 GHz, pulse widths of 0.333, 2.0 and 4 ns, and pulse repetition rates of 1.11 x 10(6), 100 x 10(6), and 181.18 x 10(6) pps. The classical Mie solution was modified for a train of incident pulses that was represented by a Fourier series, and the fast-Fourier transform was used to sum the series. Computationally, the technique proved to be feasible and less expensive than we expected. The calculated field patterns show that the sphere's physical dimensions and the internal wavelength of the carrier greatly influence the nature of pulse-train propagation in the sphere. Harmonics having internal wavelengths nearly equal to the radius of the sphere produce most of the absorption; other harmonics produce little absorption. An intense hot spot is observed in spheres with radii that match the carriers' wavelengths. PMID- 1750827 TI - Japanese encephalitis virus (JEV): potentiation of lethality in mice by microwave radiation. AB - The expression of Japanese Encephalitis Virus (JEV) lethality in mice requires entry of the virus into the central nervous system. This entry is presumably through the capillary endothelial cells (CEC), because entry between CECs is inhibited by bands of circumferential tight-junctions. A viremic stage occurs during the first 4 to 5 days after JEV administration in mice, and both microwave radiation (2.45-GHz, continuous wave, 10-min exposure) and hypercarbia were employed to increase CEC permeability to JEV. Exposure to microwaves at power densities of 10-50 mW/cm2 resulted in a dose-dependent increase in JEV-induced lethality. Mice did not become tolerant or sensitized to microwave potentiation of JEV-induced mortality because 4 daily exposures at 10 or 50 mW/cm2 (SARS, approximately 24-98 W/kg) did not alter the lethality pattern to subsequent microwave radiation of JEV-exposed animals. Similarly, hypercarbia (5, 10, and 20% CO2) was observed to produce a dose-dependent increase in JEV-induced lethality. Both microwave radiation and hypercarbia are thought to promote pinocytosis in CNS capillary endothelial cells. This may be one mechanism by which they enhance JEV-induced lethality in adult Swiss-Cox mice. PMID- 1750828 TI - Electric fields induced in chicken eggs by 60-Hz magnetic fields and the dosimetric importance of biological membranes. AB - Chicken eggs are convenient models for observing the effects of inhomogeneities and variations, such as those found in biological membranes and in cellular conductivities, on the distribution of internal electric fields as induced by exposure to magnetic fields. The vitelline membrane separates the yolk, which has a conductivity of 0.26 S/m, from the white, which has a conductivity of 0.85 S/m. A miniaturized probe with 2.4-mm resolution was used to measure induced fields in eggs placed in a uniform, 1-mT magnetic field at 60 Hz. The E fields induced in eggs with homogenized contents agreed with expectations based on simple theory. Results were similar to intact eggs unless the probe moved the yolk off-center, which greatly perturbed the induced fields. A more reproducible arrangement, which consisted of saline-agar filled dishes with a hole cut for test samples, was developed to enhance definition of electrical parameters. With this test system, the vitelline membrane was found to be responsible for most of the perturbation of the induced field, because it electrically isolates the yolk from the surrounding white. From a theoretical viewpoint, this dosimetry for the macroscopic egg yolk is analogous to the interaction of fields with microscopic cells. These findings may have important implications for research on biological effects of ELF electromagnetic fields, especially for studies of avian embryonic development. PMID- 1750829 TI - Effects of exposure to a 60-kV/m, 60-Hz electric field on the social behavior of baboons. AB - We found in a previously reported study that exposure to a 30-kV/m, 60-Hz electric field had significant effects on the social behavior of baboons. However, it was not established whether or not the effects were related specifically to the 30-kV/m intensity of the field. A new experiment was conducted to determine whether or not exposure to a 60-Hz electric field at 60 kV/m would produce like changes in the baboons' social behavior. We exposed one group of eight male baboons to an electric field 12 hours a day, 7 days a week, for 6 weeks. A second group of eight animals was maintained under sham-exposure (control) conditions. Rates of performing on each of six categories of social behavior and on four categories of nonsocial behavior were used as criteria for comparing exposed with unexposed subjects and for within-group comparisons during three six-week experimental periods: Pre-Exposure, Exposure, and Post-Exposure. The results indicate that (1) during the exposure period, exposed animals exhibited statistically significant differences from controls in means of performance rates based on several behavioral categories; (2) across all three periods, within-group comparisons revealed that behaviors of exposed baboons were significantly affected by exposure to the electric field; (3) changes in performance levels probably reflect a stress response to the electric field; and (4) the means of response rates of animals exposed at 60 kV/m were higher, but not double, those of animals exposed at 30 kV/m. As in the 30-kV/m experiment, animals exposed at 60 kV/m exhibited significant differences in performances of Passive Affinity, Tension, and Stereotypy. Mean rates of performing these categories were 122% (Passive Affinity), 48% (Tension), and 40% (Stereotypy) higher in the exposed group than in the control group during exposure to the 60 kV/m field. PMID- 1750830 TI - In vitro exposure parameters with linearly and circularly polarized ELF magnetic fields. PMID- 1750831 TI - [Electron microscopy of alpha-latrotoxin from the venom of the black widow spider Latrodectus mactans tredecimguttatus]. AB - Two-dimensional crystals of alpha-latrotoxin from the venom of black widow spider (Latrodectus mactans tredecimguttatus) were studied by the negative staining electron microscopy. Two-dimensional crystals were obtained by adsorption of the protein solution with a high Mg2+ concentration on carbon-coated electron microscopy grids. The crystals were about 0.4 mkm in size, had the unit cell parameters: a = b = 15.55 nm, gamma = 90 degrees, p4 plane group symmetry. The contour map of a stain-excluding region of such crystals was calculated by the Fourier-filtering procedure at about 4 nm resolution. The calculation of molecular weight of the unit cell, with the symmetry p4 taken into account, showed that alpha-latrotoxin particles, revealed by negative staining, consisted of 4 or 8 protomers. PMID- 1750832 TI - [Tyrosyl-tRNA-synthetase from bovine liver. Functional role of histidine residues]. AB - A specific chemical modification of histidyl residues in tyrosyl-tRNA synthetase by diethyl pyrocarbonate was performed. It is shown that five of sixteen histidyl residues can react with diethyl pyrocarbonate in the native conditions. Modification of two histidyl residues per dimer results in the inactivation of tyrosyl-tRNA synthetase in both steps of the tRNATyr aminoacylation. All substrates protect tyrosyl-tRNA synthetase against inactivation with diethyl pyrocarbonate, the most effective protector being combination of ATP and tyrosine. Histidyl residues of tyrosyl-tRNA synthetase are suggested to be involved in the catalytic mechanism of aminoacylation of tRNATyr. PMID- 1750833 TI - [Anomalous behavior of certain proteins having an isoelectric point near 4.5 during their precipitation from aqueous solutions from organic solvents]. PMID- 1750834 TI - [Ligation of DNA containing a 5'-terminal thiophosphate group, with T4-DNA ligase]. PMID- 1750835 TI - [Enzymatic synthesis of acyl peptides containing p-nitroanilides of basic amino acids]. AB - A method is suggested for synthesis of acylpeptides, containing arginine or lysine p-nitroanilides at the C-terminus, via the acyl transfer reaction catalyzed by the Bacillus subtilis serine proteinase. Acyl-di- and acyltripeptide ethers with L- and D-amino acids were used as the carboxyl component taken in a twofold excess. When the concentration of dimethylformamide increases, the hydrolysis of the initial ether and the reaction product diminishes. Because of the enzyme inactivation by dimethylformamide the latter's optimal concentration is 70-80%. PMID- 1750836 TI - [Synthesis of the tripeptide glycyl-L-leucyl-L-phenylalanine and its analogs]. AB - Peptide Gly-L-Leu-L-Phe and its derivatives were synthesized by the C-end elongation utilizing DCC/HOBT technique and by enzymatic route with the help of papain using esters of N-benzyloxycarbonyl-glycine and -L-leucine as acyl donors have been suggested. The chemical, similarly to the enzymatic, synthesis was not accompanied by racemization. Conditions for HPLC separation and preparative isolation of the enzymatic reaction products were developed. PMID- 1750837 TI - [Synthesis, conversion and biological activity of 5-substituted 2'-deoxyuridines modified by carbohydrates]. AB - 5-Benzyloxymethyl(Bom)-2'-deoxyuridine and its alpha-anomer were used as the key compounds for syntheses of thymidine analogues or 3'-derivatives. Anomeric 5-Bom 2'-deoxyuridines were synthesized from 5-Bom-uracil and 2-deoxy-3,5-di-O-p-toluyl alpha-D-ribo-furanosyl chloride by means of the silyl method. 5-Bom-2' deoxyuridine was transformed successively to 3',5'-di-O-mesyl derivative, 2,3' anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofuranosyl)-5-Bom-uracil and 3'-azido 2',3'-dideoxy-5-Bom-uridine. Treatment of the last with SnCl4 in methylene dichloride--methanol led to 3'-azido-2',3'-dideoxy-5-methoxymethyluridine. Under the same conditions the 5-methoxymethyl derivative was obtained from 3',5'-di-O-p toluyl-5-Bom-2'-deoxyuridine. Interaction of 1-(2-deoxy-alpha-D-ribofuranosyl)-4 Bom-uracil with SnCl4 in methylene dichloride as well as the hydrogen transfer hydrogenolysis in the presence of cyclohexene and Pd(OH)2/C in ethanol led to 1 (2-deoxy-alpha-D-ribofuranosyl)-5-hydroxymethyluracil. Only 3'-azido-2',3' dideoxy-5-Bom-uridine showed a cytotoxic activity against CaOv cells in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA by 78.8-95.1%. Elucidation of antitumor activity in vivo showed that this nucleoside inhibits growth of solid tumours, Ca755 and LLC, by 79 and 79-83%, respectively, but has no therapeutic effect against lympholeukemia P388. PMID- 1750838 TI - [Antigenic properties of synthetic peptides of hexon proteins human adenovirus type 2 fiber]. PMID- 1750839 TI - [A rapid method of complete deblocking of synthetic oligonucleotides]. PMID- 1750840 TI - Professional practices perspective on clinical outcomes. PMID- 1750841 TI - A new institute. A promising future of research. PMID- 1750842 TI - Responsible conduct of research. PMID- 1750843 TI - Managing heritable hearing loss: the audiologist's role. PMID- 1750845 TI - Beyond tradition. PMID- 1750844 TI - A research mentoring process. PMID- 1750846 TI - Oversight noted. PMID- 1750847 TI - Scholarly publications alive and well in ASHA. PMID- 1750848 TI - Historically black and majority-white universities. AB - This paper details a cooperative sisterhood minority recruitment and retention agreement that was established between a predominantly White university and a historically Black university for the purpose of increasing the numbers of minority personnel in speech-language pathology and audiology. This paper also provides some suggestions for universities that may wish to implement a similar model. The program is still in its infancy. It is too early to determine how well a sisterhood agreement is able to provide a bridge of financial, academic, and emotional support to enable minority students to be successful. With continued experience with our new sisterhood relationship, we will be able to evaluate the program, make changes to improve it, and eventually determine whether or not the program is meeting the purpose for which it was designed. Faculty from both universities also look forward to collaborating on research projects and other scholarly activities. In the meantime, however, given the shortage of minority personnel in our profession, it seemed appropriate to offer the sisterhood concept as one means by which universities can help alleviate this critical problem. PMID- 1750849 TI - The professional doctorate: opinions of members with doctorates and of directors of doctoral programs. PMID- 1750851 TI - International Association of Laryngectomees. PMID- 1750850 TI - Medicare speech-language pathology medical review edits. PMID- 1750852 TI - Meniere's disease. PMID- 1750853 TI - "Thunderous" motor sports. PMID- 1750854 TI - Animal research. PMID- 1750855 TI - Museum proposed. PMID- 1750856 TI - Alternative testing proposed. PMID- 1750857 TI - Cultural diversity in the elderly population. PMID- 1750858 TI - Universal health care: the time has come. PMID- 1750859 TI - Dr Jack Kevorkian and medically assisted suicide. A patient's right to a good death. PMID- 1750860 TI - Transplantation of purified autologous fat: a 3-year follow-up is disappointing. AB - The idea of autologous fat microtransplants has recently resurfaced because of interest by the press. Past experiments have shown that small amounts of fat may be transplanted with an expected survival rate between 10 and 50 percent without ectodermis. A great fund of knowledge exists showing that skin grafts will survive quite dependably if their thickness is up to about 0.0020 inch. For the first week or so, they live by diffusion and inosculation, and then neovascularization enables them to continue viability. I have developed a technique whereby fat is harvested through a blunt cannula with minimal vacuum to prevent explosion of the cellular fat globules. Fibrin and cellular debris are removed, and the fat globules are separated from the free fat, blood, and other constituents of the aspirate. Individual, free-floating 1- to 3-mm adipose fragments are then suspended in nutrient solution and injected through an 18 gauge needle. Multiple radial pathways, with each fat segment being separated from the other by host tissue, maximizes the host-prosthesis interface and the possibility for exchange of nutrients. I have attempted this procedure in more than 100 patients with widely varying results. In acne pits of the face, no significant improvement could be noted 6 weeks after injection. For the first few weeks, a near-perfect result was obtained, but none of these transplants in scarred areas of this kind have been of benefit. Injection of 10 to 50 cc in other areas has resulted in some cells (perhaps 10 percent) surviving over 2 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1750861 TI - Smoking and older chest physicians. PMID- 1750862 TI - The changing face of asthma. PMID- 1750863 TI - Endothelin. Key to coronary vasospasm? PMID- 1750864 TI - Bioavailable testosterone in salivary glands. PMID- 1750865 TI - Iodine deficiency disorders and infertility. PMID- 1750866 TI - Vulval reconstruction by free tissue transfer. Case report. PMID- 1750867 TI - Setting up and using a cardiac monitor. PMID- 1750868 TI - Dynamic urethral pressure profilometry pressure transmission ratio: what do the numbers really mean? AB - Sixty-three women with genuine stress urinary incontinence were evaluated urodynamically both before and after modified Burch colposuspension to determine the association between pressure transmission ratio and leakage of urine during dynamic urethral pressure profile and the effect of surgery on pressure transmission ratio. Preoperatively, there was no difference in pressure transmission ratios between urethral pressure profiles associated with leakage of urine and those without urine leakage. Postoperatively, there were differences in pressure transmission ratios between leak and nonleak profiles in the sitting full and supine positions (P less than .001). We could not determine a threshold pressure transmission ratio that was more characteristically associated with leakage of urine. Finally, preoperative pressure transmission ratios were not associated with surgical success, but the higher the postoperative pressure transmission ratio, the more likely the surgery was to be successful (P = .023). In addition, the greater the difference between preoperative and postoperative pressure transmission ratios, the more likely was a cure (P = .011). The pressure transmission ratio may not be helpful in discriminating leak from nonleak dynamic urethral pressure profiles, and there may not be a threshold pressure transmission ratio below which patients characteristically leak urine. However, comparison of preoperative and postoperative pressure transmission ratios is helpful in determining the adequacy of surgical correction of the anatomical defect associated with genuine stress incontinence. PMID- 1750869 TI - Standardized percentile curves of body-mass index for children and adolescents. AB - Weight-for-height indexes are often used in the clinical assessment of obesity in children and adolescents. The direct measurement of adiposity, using hydrostatic weighing and other techniques, is not feasible in studies involving young children or with large numbers of older subjects. Ratios of weight relative to height, such as the body-mass index (weight/height), may be used as indirect measures of obesity and correlate with more direct measures of adiposity. Using data from the First National Health and Nutrition Examination Study, 1971 to 1974, standardized percentile curves of body-mass index for white children and adolescents were developed. These curves may be used to monitor the body-mass index of white children and adolescents longitudinally and for comparing an individual with others of the same sex and age. PMID- 1750870 TI - Training for the new contract. PMID- 1750871 TI - Effectiveness of ward based opportunistic immunisation policy. PMID- 1750872 TI - Effects of dietary supplementation on work performance in Gambian laborers. AB - The effect of food supplementation on productivity of Gambian subsistence farmers was studied during a natural food shortage induced by the annual hungry season. Sixteen men in two groups matched for weight, height, hemoglobin, and physical work capacity followed a crossover protocol with 6-wk supplementation and control periods. Productivity was assessed over the final 3 wk of each period by quantifying piece-rate-paid road building. Supplementation comprised an ad libitum supply of highly palatable energy-dense food provided three times daily. Outcome variables were total loads transported, loads per working hour, time per load, total energy expenditure assessed by doubly labeled water and heart-rate monitoring, postwork activity, and anthropometry. Body weight decreased during control periods, indicating a real energy deficit, and increased during supplementation in both groups. Supplementation had no significant impact on productivity variables. Energy-deficient men can maintain maximal productivity over short periods if sufficiently motivated but at the expense of body weight. PMID- 1750873 TI - Sociocultural correlates of eating disorders among Asian schoolgirls in Bradford. AB - A survey of 204 south-Asian and 355 Caucasian schoolgirls was conducted in Bradford using the EAT-26 and the BSQ. At interview, seven Asian girls and two Caucasian girls met DSM-III-R criteria for bulimia nervosa, yielding a prevalence of 3.4% and 0.6% respectively. One Asian girl met DSM-III-R criteria for anorexia nervosa. Factor analyses of the EAT and BSQ supported their cross-cultural conceptual equivalence in this south-Asian population. Among the Asians, high EAT and BSQ scores were associated with a more traditional cultural orientation and not with greater Westernisation. It is probable that these findings reflect the cultural and familial difficulties faced by these Asian girls growing up in Britain. PMID- 1750874 TI - Let's provide primary care to all uninsured Americans--now! AB - Gridlock in the political process makes comprehensive health insurance for the uninsured an unlikely prospect in the near future. While the debate continues, we should provide basic primary care services to all uninsured Americans. Primary care is the most economical safety net we can offer our citizens. By prepaying participating physicians, we could provide this needed care at a cost the nation could afford and with excellent prospects for controlling expenditures over time. PMID- 1750875 TI - Absence of siblings--a risk factor for hypertension? PMID- 1750876 TI - The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin alpha 6 beta 4. AB - We previously reported that altered expression of the A9 antigen (defined by monoclonal antibody UM-A9) is a predictive marker of early recurrence and progression of squamous cell carcinoma (SCC). In normal squamous cells A9 expression is limited to the site of contact with the basement membrane in vivo and the culture surface in vitro, whereas aggressive SCCs exhibit loss of polarity and increased intensity of A9 expression. The potential relationship of the A9 antigen to structures known to be involved in cell adhesion was analyzed by immunobiochemical and cell adhesion assays. UM-A9 precipitates a complex of protein chains reminiscent of the alpha and beta heterodimer glycoproteins that characterize the integrin family of extracellular matrix receptors. Proteins were isolated from A9-positive cells using UM-A9 and well-defined antibodies specific for integrin alpha and beta chains. UM-A9, anti-alpha 6, and anti-beta 4 monoclonal antibodies (mAbs) all precipitated proteins with comparable electrophoretic mobilities. Furthermore, UM-A9 mAb precleared the SCC alpha 6 beta 4 integrin complex isolated with anti-alpha 6 or anti-beta 4 mAbs but not that isolated by anti-beta 1 mAb. The isoelectric points of the A9 complex chains were consistent with those reported for alpha 6 and beta 4. Three of the polypeptide chains (140, 175, and 205 kDa) precipitated by UM-A9 showed peptide homology to one another and to the beta 4 chain precipitated by mAb 439-9B. The A9/alpha 6 subunit is composed of 125- and 30-kDa chains and was distinguished from beta 4 and beta 1 chains by its peptide map and isoelectric point. UM-A9 binds to an epitope common to the beta 4 subunits since in pulse-chase analysis the beta 4 species are precipitated at an early time point, whereas detection of alpha-subunit synthesis is detected during assembly of the mature complex. Immunoprecipitation and preclearing experiments demonstrated that in SCC the alpha 6 subunit is associated primarily with the beta 4 species and not with the 130-kDa beta 1 subunit. In cell adhesion assays on extracellular matrix proteins, the alpha 6-specific GoH3 mAb inhibited binding of SCC to laminin, suggesting that alpha 6 beta 4 may function as a laminin receptor in SCC. These data and our prior observations showing an association between altered A9 expression and early recurrence in SCC provide the first evidence that altered expression of alpha 6 beta 4 integrin is associated with the clinical behavior of human squamous cell carcinomas. PMID- 1750877 TI - Potential health effects of greenhouse effect and ozone layer depletion in Australia. AB - OBJECTIVE: To identify potential health effects of the greenhouse effect and ozone layer depletion in Australia. DATA SOURCES: Data were derived from a number of sources: (i) published articles accessed from relevant databases in the disciplines of health, public health and climatology over the past 20 years; (ii) published conference proceedings, review monographs and government reports covering the topic; (iii) a survey of experts in public health and climatology/geography (150 individuals were surveyed in the first phase with a 63% response rate); and (iv) a consensus conference in which 22 invited experts reviewed the results of the literature review and survey and a second conference in which 18 senior members of the health bureaucracy and public health profession considered the implications of the findings. STUDY SELECTION: Over 200 published articles or monographs were reviewed. Criteria for selection were whether the papers contributed information to the objectives of the review. DATA EXTRACTION: Because of the nature of the problem under investigation, predictions based on reasonable scientific assumptions were the major content of the review rather than conclusions based on scientific research. DATA SYNTHESIS: The major predicted health effects of long-term climatic change in Australia are skin and eye damage from increased ultraviolet radiation exposure, increased incidence of some respiratory diseases, vector-borne and water-borne diseases, and the social and physical effects of natural hazards and social and economic restructuring. The most vulnerable groups include the aged, the very young, the chronically ill, those living in poorly designed neighbourhoods and those working in outdoor occupations or heavy industry. CONCLUSIONS: The potential effects on health of long-term climatic change cover the broad spectrum of public health concerns. Detailed predictions of likely problems in specific geographic areas are not yet possible, but progressive development of such predictive capability is a high priority. Doctors will have an increasingly important role in monitoring local health status and participating in disease prevention and surveillance programmes. PMID- 1750878 TI - Controlling adverse effects of chemotherapy. PMID- 1750879 TI - Continuing education of general dental practitioners. PMID- 1750880 TI - A dual approach to the AIDS epidemic. PMID- 1750881 TI - Surgical treatment of obstructive sleep apnea syndrome (OSAS) AB - Obstructive sleep apnea syndrome patients usually present with multiple areas of anatomic disproportions. The site or sites of obstruction must be accurately diagnosed preoperatively by a systematic means of examining the patient. This includes nasopharyngoscopy with Muller maneuver and sometimes cephalometrics. The surgical treatment is individualized to the site or sites of obstruction and can include tracheostomy, septoplasty, UPPP, geniohyoid advancement and suspension of the hyoid. For extreme cases advancement of the maxilla, mandible and hyoid bone are sometimes necessary. PMID- 1750882 TI - Ultraviolet A radiation: staying within the pale. PMID- 1750883 TI - Is bioethics really a "new" medical specialty? PMID- 1750884 TI - Maternity services: the shaping of things to come. PMID- 1750885 TI - Junior doctors, nurses, and drips. PMID- 1750886 TI - How Europe regulates its genes. PMID- 1750887 TI - A user's guide to the T-test. PMID- 1750888 TI - Misuse of streptokinase in dissecting aortic aneurysm. PMID- 1750889 TI - Sternal-clavicular plasmacytomas with atypical morphology. PMID- 1750890 TI - Deafness in children. PMID- 1750891 TI - Appraising journals' reviewing procedures. PMID- 1750892 TI - Late bleeding after endoscopic sphincterotomy for bile duct calculi. PMID- 1750893 TI - Identification of the interpleural space. PMID- 1750894 TI - Unrecognised HIV related deaths. PMID- 1750895 TI - Skewed distributions and parametric tests. PMID- 1750896 TI - Present day anatomy. PMID- 1750897 TI - Cooling jacket modifications. PMID- 1750898 TI - Rifampicin in rheumatoid arthritis. PMID- 1750899 TI - Occupational health research needs in developing countries. PMID- 1750900 TI - Silicone intraocular lens implant discoloration in humans. PMID- 1750901 TI - Vitrectomy for prevention of macular hole study. PMID- 1750902 TI - A new Igk-V gene family in the mouse. PMID- 1750903 TI - Response to article by Foote et al. PMID- 1750904 TI - Topical (bathwater) PUVA therapy. PMID- 1750905 TI - "Eliminating" hyperthyroidism. PMID- 1750906 TI - Let's provide primary care to all uninsured Americans--now. PMID- 1750907 TI - The Marlboro Grand Prix. PMID- 1750908 TI - Transoral approach for removal of intradural lesions at the craniocervical junction. PMID- 1750909 TI - Localization of transected wire. PMID- 1750910 TI - Managing hypertension. PMID- 1750911 TI - Uric acid in pregnancy and preeclampsia: an alternative hypothesis. PMID- 1750912 TI - A morphological and immunological study of human placental bed biopsies in miscarriage. PMID- 1750913 TI - Selection of controls. PMID- 1750914 TI - Standardized care plans. PMID- 1750915 TI - Beta-carotene didn't prevent cancer: what's up doc? PMID- 1750916 TI - The impact of volume on outcome in seriously injured trauma patients: two years' experience of the Chicago trauma system. PMID- 1750917 TI - Management of prenatally diagnosed fetal abnormality. PMID- 1750918 TI - Acute asthma in children. PMID- 1750919 TI - Clinical disagreement. PMID- 1750920 TI - Relation of blood pressure to number of siblings. PMID- 1750921 TI - Surgical treatment of obstructive sleep apnea. PMID- 1750922 TI - [Infection of knee endoprosthesis]. AB - In knee arthroplasties, infection was and still is the most decisive factor with respect to the end result. Control of infection without removal of the endoprosthesis can be achieved only when an early revision is performed in the first 6 weeks after the arthroplasty. Half-hearted antibiotic medication alone is an unsuitable remedy. Therefore, an infection must be diagnosed without delay and followed up by decisive management. Clinical and laboratory data must be considered together and must supplement each other. Late infections need temporary or permanent removal of the endoprosthesis as a prerequisite for getting rid of the infection. Reimplantation and arthrodesis should be done in a two-stage procedure after the infection is healed. Reimplantation should be restricted to cases in which the infection is definitely under control and in which there is a good bone stock. Arthrodesis is still the treatment of choice, especially in patients with bony defects in the metaphysis of the femur and tibia. Arthrodesis also needs good soft tissue cover, and to prevent a reinfection in this dangerous area we suggest the use of antibiotic-releasing bone plates for stabilisation. External fixation has a high percentage of pintrack infections and often cannot be applied long enough; thus non-unions are the logical consequence. PMID- 1750923 TI - Academic boycott. PMID- 1750924 TI - Effects of fish-oil ingestion on cardiovascular risk factors. PMID- 1750925 TI - Genital self-amputation and the Klingsor syndrome. PMID- 1750926 TI - Further functions of IL-6. PMID- 1750927 TI - Ancient technique of olive detection. PMID- 1750928 TI - Manometry vs. pH step-up. PMID- 1750929 TI - The CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin alpha 4 beta 1. Inhibition of alpha 4 beta 1 function by RGD peptide homologues. AB - The alternatively spliced type III connecting segment (IIICS) region of fibronectin contains two distinct sites that support the adhesion of melanoma cells. These sites are contained within the synthetic peptides CS1 and CS5 (residues 1-25 and 90-109 of the IIICS, respectively). Recently, the cellular receptor for the CS1 site has been identified as the integrin heterodimer alpha 4 beta 1. In this report, we have investigated the role of the CS5 sequence in melanoma cell adhesion and the identity of its receptor. Adhesion to CS5, when presented to cells as an immobilized IgG conjugate, was blocked by antifunctional monoclonal antibodies directed against either the alpha 4 or beta 1 integrin subunits, but not by antibodies against other subunits, implying that alpha 4 beta 1 is also the receptor for CS5. In peptide inhibition experiments, CS5 was inhibitory for melanoma cell spreading on both CS5-IgG and CS1-IgG conjugates; conversely, CS1 inhibited spreading on both CS1-IgG and CS5-IgG. In both cases, peptide inhibition could be outcompeted by increasing the concentration of substrate-bound conjugate. These results suggest that CS1 and CS5 are recognized by the same or overlapping sites on alpha 4 beta 1. The minimal active sequence within CS5, the tetrapeptide Arg-Glu-Asp-Val (REDV), is somewhat related to the Arg-Gly-Asp-Ser (RGDS) sequence that represents a major active site in the central cell-binding domain (CCBD) of fibronectin. When RGDS peptide homologues were tested for their ability to inhibit spreading of melanoma cells on CS1- and CS5-IgG conjugates, GRGDS, GRGES, and REDV were found to be inhibitory, while GRDGS had no effect. In contrast, spreading on a fibronectin fragment containing the CCBD was inhibited by GRGDS only. GRGDS was also able to elute alpha 4 beta 1 specifically from a CS1 affinity column, confirming directly that alpha 4 beta 1 IIICS interactions are sensitive to peptides containing this recognition motif. Because the minimal active sequence within CS1 is the tripeptide Leu-Asp-Val (LDV; Komoriya et al., manuscript submitted for publication), these findings together define a new adhesive recognition sequence, X-Asp-Y, used by alpha 4 beta 1 for binding to fibronectin. The central aspartate residue in this tripeptide is almost always essential, but some flexibility in the amino acid residues at X (glycine, leucine, or glutamic acid) and Y (serine or valine) is tolerated. Potential models for the interaction of the IIICS region with alpha 4 beta 1 are discussed. PMID- 1750930 TI - Restoration by a 35K membrane protein of peroxisome assembly in a peroxisome deficient mammalian cell mutant. AB - Peroxisomes are among the intracellular organelles of eukaryotic cells that contain specialized sets of enzymes with specific functions. Little is known of membranous components involved in assembly of the intracellular compartments. We isolated two peroxisome-deficient and mutually complementary, Chinese hamster ovary cell mutants, Z65 and Z24, which closely resembled fibroblasts from patients with autosomal recessive, peroxisome-defective disorders such as Zellweger syndrome. These patients show characteristic dysmorphism, severe hypotonia, psychomotor retardation, and peroxisomal dysfunctions and rarely survive early childhood. Here we report what seems to be the first direct cloning and characterization of a complementary DNA encoding a peroxisomal membrane protein of relative molecular mass 35,000 (Mr35K) that restores the biogenesis of peroxisomes and complements the defect of peroxisomal functions in the mutant Z65. PMID- 1750931 TI - Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. I. Production, isolation and physico-chemical and biological properties. AB - Penicillium purpurogenum FO-608, a soil isolate, was found to produce a series of new inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Three active compounds, designated purpactins, A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. Purpactins inhibit ACAT activity in an enzyme assay system using rat liver microsomes with IC50 values of 121 approximately 126 microM. Purpactin A also inhibited cholesterol ester formation in J 774 macrophages, indicating the inhibition of ACAT activity in the living cells by purpactin A. PMID- 1750932 TI - The effects of graft tensioning on the laxity and kinematics of the anterior cruciate ligament reconstructed knee. AB - An in vitro study of eight cadaveric knees was conducted to investigate the effect of initial graft tension on the laxity and full three-dimensional kinematics of the anterior cruciate ligament reconstructed knee. A parallel strand, prototype, expanded polytetrafluoroethylene graft (W. L. Gore and Associates, Flagstaff, AZ, U.S.A.) was used. The graft was placed in the over-the top position with initial tensions of 18, 36, 54, 72, and 90 N applied with the knee in full extension or at 30 degrees of flexion. The motion of the tibia relative to the femur was measured by a 6 degrees-of-freedom spatial linkage, and the applied forces and moments, the quadriceps force, and the graft tension were measured by load cells. Near normal anterior laxity in the Lachman test was restored with all the tested initial graft tensions. However, over constraint, posterior, lateral, and external tibial subluxation, and abnormalities in joint stiffness developed as the initial graft tension increased. Graft tension-related posterior tibial subluxation resulted in an increase in quadriceps force needed to achieve full extension. PMID- 1750933 TI - Double-layered lateral meniscus: a newly found anomaly. AB - We report two cases of a double lateral meniscus, with one meniscus overlying another. It was characteristic that the upper accessory meniscus was connected at the posterior horn and middle segments of the lower meniscus. Symptoms in both cases disappeared after resecting the upper meniscus arthroscopically. There was no evidence of tear or other pathologic finding in the meniscus, which showed no disturbance of the fiber arrangement. PMID- 1750934 TI - Contaminated patellar tendon grafts: incidence of positive cultures and efficacy of an antibiotic solution soak--an in vitro study. AB - The incidence of positive cultures after contamination of sterile patellar tendon grafts in an operating room environment was studied in 10 specimens. The grafts were dropped on the floor for 3 min and then cultured. Six of the 10 grafts (60%) had a positive culture at 10 days. To test the efficacy of an antibiotic solution on cleansing contaminated grafts, 10 additional grafts were dropped on the floor for 3 min. Before the grafts were cultured they were soaked in a sterile saline solution containing bacitracin (33.33 U/ml) and polymyxin B (333.33 U/ml) for 15 min. Thirty percent of these grafts (3 of 10) cultured positive at 10 days. In each case the bacterial contaminant was found to be sensitive to one of the antibiotic agents used in the cleansing solution. The results of this study suggest that although soaking contaminated grafts in this antibiotic solution for 15 min may reduce the incidence of positive cultures, it still results in a 30% incidence of nonsterile grafts. PMID- 1750935 TI - Assessing arthroscopic notchplasty. AB - To evaluate the ability to perform a widening arthroscopic intercondylar notchplasty as part of an anterior cruciate ligament reconstruction, 20 patients had notch-width index measurements compared with either preoperative or normal side values. The notch-width index increased an average of 0.062, correlating with absolute notch widening of 4-6 mm. This study provides in vivo evidence that notchplasty widening can be reproducibly performed arthroscopically. The optimal notch width for reconstructive anterior cruciate ligament surgery has yet to be determined. PMID- 1750936 TI - The effect of tourniquet use and hemovac drainage on postoperative hemarthrosis. AB - Postoperative hemarthrosis is the most common reported complication after arthroscopic knee surgery. The purpose of this study was to determine the effects of hemovac drainage and tourniquet use on the incidence of postoperative hemarthrosis. Sixty patients who had undergone arthroscopic knee surgery were divided into groups based on tourniquet use and whether a drain was used postoperatively. At follow-up, patients had range of motion recorded, and clinical assessment of their hemarthrosis (Grades 0 through 4). Patients who had a hemovac drain used postoperatively, and those patients who did not have a tourniquet used, had fewer hemarthroses and a greater range of motion at all periods of follow-up. We conclude that use of a drain can decrease the incidence of hemarthrosis and allow patients to regain an active range of motion sooner. Also, the routine use of a tourniquet should be avoided because of its correlation with hemarthrosis. PMID- 1750937 TI - Lateral retinacular release for patellofemoral pain in the older patient. AB - Lateral release for patellofemoral pain was performed on 39 knees in 34 patients aged greater than or equal to 30 years. At a mean follow-up of 6 years, there were 56% good or excellent results. Only 20% of patients did not achieve any benefit from the procedure. Although these results may not be as good as in the younger patient, this low morbidity procedure is nevertheless useful in the management of the older patient with patellofemoral malalignment. PMID- 1750938 TI - Risks of neurovascular injury in elbow arthroscopy: starting anteromedially or anterolaterally? AB - A cadaver dissection study was performed to study the risks of neurovascular damage in elbow arthroscopy. The risk of injury to the radial nerve in the anterolateral approach was higher than the risk of damaging the median nerve in the anteromedial approach. In addition, starting medially may contribute to accurate placement of the anterolateral portal and may further help to decrease the risk of injuring the radial nerve. Therefore, starting with an anteromedial approach has several advantages above starting anterolaterally. PMID- 1750939 TI - Arthroscopic subacromial decompression: results in advanced impingement syndrome. AB - A study group composed of 25 shoulders in 24 patients underwent arthroscopic subacromial decompression for advanced impingement syndrome. There were no full thickness rotator cuff tears, biceps tendon ruptures, significant acromioclavicular arthrosis, or evidence of glenohumeral instability. Twenty men and four women ranging in age from 18 to 63 years (mean age 37) with dominant arm involvement in 17/24 were evaluated for an average follow-up of 20.3 months (range 14-32) postoperatively. Operative results were based on the UCLA shoulder rating scale. Eighty-eight percent of the cases (22/25) had good or excellent results. Twelve percent had fair results (3/25). There were no poor results. The average UCLA pain score improved from 2.6 preoperative (constant pain) to 7.8 postoperative (occasional pain). Ninety-two percent of the patients were satisfied, said they were better, and that they would have the surgery again. Arthroscopic subacromial decompression is recommended as an alternative to open anterior acromioplasty in advanced impingement syndrome. PMID- 1750940 TI - Extrusion of the medial meniscus. AB - Disruption of the anchoring points of the menisci of the knee has been hypothesized to result in subluxation of the affected meniscus from the articular surface. A case report of such an extrusion of the medial meniscus is presented. Medial subluxation of the meniscus from the tibiofemoral articulation occurred as a result of avulsion of the posterior horn with concomitant medial collateral and posterior cruciate ligament injuries. PMID- 1750941 TI - Precision acromioplasty in arthroscopic subacromial decompression of the shoulder. AB - Arthroscopic techniques for subacromial decompression have been criticized for lack of precision in resecting the anterior acromial undersurface and evaluating the amount of bone resected. The goal of subacromial decompression is production of a flat undersurface for the acromion and acromioclavicular joint, thus enlarging the supraspinatus outlet and deterring impingement. Achieving this goal using the arthroscope requires preoperative evaluation of the acromial morphology, planning of the dimensions of bony resection, a reproducible acromioplasty method with intraoperative evaluation of the adequacy of resection, and postoperative confirmation of the resulting acromial shape. A precise technique for arthroscopic acromioplasty has been developed in the course of performing over 200 shoulder arthroscopies. This method adheres to conventional open surgical goals for bony resection and allows for reliable intraoperative evaluation of the result. Using this technique, over 90% good and excellent results may be achieved in treatment of stage II subacromial impingement syndrome. PMID- 1750942 TI - An arthroscopic technique of demonstrating the pathomechanics of the suprapatellar plica. AB - The suprapatellar plica or incomplete suprapatellar septum of the knee is a recognized cause of knee pain in some patients and appears to exist in others without causing any symptoms. To date no clear method of demonstrating the pathomechanics of the suprapatellar plica by arthroscopic means has been described. This article describes a new technique of visualizing this structure arthroscopically and demonstrating the mechanism of its morbidity. By the use of a proximal viewpoint via the lateral suprapatellar portal, we have shown that the suprapatellar plica impinges on the medial femoral condyle and is trapped between the quadriceps mechanism and the femoral trochlea when the knee is flexed beyond 70 degrees. We conclude that our arthroscopic method may show the mechanism of production of symptoms of the pathological suprapatellar plica. PMID- 1750943 TI - Cost-effectiveness study of magnetic resonance (MR) scanning of the acutely injured knee. PMID- 1750944 TI - Sequence analysis of the D1 and D2 reaction center proteins of photosystem II. AB - A compilation of 38 sequences for the D1 and 15 sequences for the D2 reaction center proteins of photosystem II is presented. The sequences have been compared and a similarity index that takes into account the degree of conservation and the quality of the changes in each position has been calculated. The similarity index is used to identify and describe functionally important domains in the D1/D2 heterodimer. Comparative hydropathy plot are presented for the aminoacid sidechains that constitute the binding domain of the tyrosine radicals, TyrZ and TyrD, in photosystem II. The structure around TyrZ is more hydrophilic than the structure around TyrD. The hydrophilic residues are clustered in the part of the binding pocket for TyrZ that is turned towards the lumenal side of the thylakoid membrane. Most prominent is the presence of two conserved carboxylic aminoacids, D1-Asp 170 and D1-Glu 189. Their respective carboxyl-groups come close in space and are proposed to constitute a metal binding site together with D1-Gln 165. The distance between the proposed metal binding site and the center of the ring of TyrZ is approximately 7 A. The cavity that constitutes the binding site for TyrD is composed of residues from the D2 protein. Its character is more hydrophobic than the TyrZ site and the environment around TyrD lacks the cluster of putative metal binding side-chains. PMID- 1750945 TI - The end of mandatory retirement and its implications for academic medicine. AB - The prohibition against age-based mandatory retirement, codified in amendments to the Age Discrimination in Employment Act (ADEA) in 1986, remains a concern in the academic medical community. A seven-year exemption covering tenured faculty expires at the end of 1993. The author reviews the legislative history of the ADEA and explores in detail the planning and management issues--and the available projections of likely faculty behavior in the future--concerning the banning of age-based mandatory retirement of higher education faculty, with special reference to the academic medical community. Although the major studies concerning the probable course of events after the seven-year exemption expires indicate that there will not be a cataclysmic effect on institutions of higher education, it is still not certain how tenured faculty will behave and how that will affect medical schools. The author cautions that the management acumen of institutional leaders will be taxed, and that medical school deans should realize this and begin the transition into the new era by improving systems for faculty evaluation and development, clarifying the financial guarantees of tenure, implementing space utilization reviews, and developing programs to make retirement attractive. PMID- 1750946 TI - Forty years of litigation involving residents and their training: II. Malpractice issues. AB - The authors reviewed 136 cases of malpractice litigation involving residents or programs of graduate medical education that were reported from 1950 through 1989. Before 1970 malpractice constituted the only area of reported litigation for residents. The number of malpractice cases involving residents increased substantially after 1975, paralleling the growth of malpractice cases nationally. The regional pattern of reported cases involving residents also corresponded with previous findings. Questions of vicarious liability, the applicable standard of care, and residents' supervision were at issue in the great majority of cases. Questions related to judicial procedure, immunity from liability, breach or causation, and informed consent were also litigated. Residents were on the side of the prevailing party in 44% of the cases. Malpractice continues to be the key legal issue facing programs of residency training. PMID- 1750947 TI - Medical students' professional ethics: defining the problems and developing resources. AB - An AAMC working group concluded that medical educators have paid insufficient attention to students' development of professional standards and to the immediate ethical dilemmas that students face as students. Its discussion of the primary determinants of medical students' ethical development focused on improving: (1) the evaluation of candidates for admission; (2) the medical school learning climate, including recognition of the challenges inherent in the increasing cultural diversity among students and patients; and (3) communication to students of expectations of professional behaviors and standards. An AAMC initiative is outlined that includes preparation of a resource book featuring cases illustrating common ethical dilemmas that medical students face, descriptions of effective honor systems, suggestions for faculty development, and an annotated bibliography. PMID- 1750948 TI - A humanities and medicine program for faculty. PMID- 1750949 TI - The contribution of medical missions: the intercultural transfer of standards and values. PMID- 1750950 TI - The Department of Veterans Affairs health care system and national health care. PMID- 1750951 TI - Broadening the focus of medical education reform. PMID- 1750952 TI - Medical students' perceptions of the practice of internal medicine. PMID- 1750953 TI - Teaching both the management and the molecular biology of sickle cell disease. PMID- 1750954 TI - Overview of recent literature on undergraduate ambulatory care education and a framework for future planning. AB - This study provides an interpretive overview of ambulatory care undergraduate education from 1979 to 1991 and identifies two major problems for medical education: (1) the difficulties inherent in the transfer of educational techniques from the hospital to the ambulatory care setting; and (2) the misuse of and lack of agreement on definitions of ambulatory care, primary care, and community-oriented primary care. The authors distinguish various types of ambulatory care and examine factors that differentiate ambulatory care and hospital sites for educating medical students, including the setting, program management, curriculum issues, evaluation, cost, faculty time, and space. Based on concepts and issues identified in the study, the authors propose a framework for planning future ambulatory care education and research. PMID- 1750955 TI - Stability of medical specialty selection at the University of Kentucky. AB - In the fall of 1989, all graduates of a 30-year-old medical college were surveyed by questionnaire concerning their motivations for their original selections of specialties, motivations for changing their specialties when such changes had occurred, and factors involved in their current choices of specialties. The 723 respondents were grouped by specialty response into one of three groups (primary care plus medicine and pediatrics subspecialties; surgery; or controllable lifestyle), and responses were statistically analyzed. The most important factors influencing initial specialty selection were perceived match of personality and specialty; technology and methodology characteristic of the specialty; and time for family activities, in that order. The ratings of the 175 respondents who stated that they had changed specialties indicated that time for avocational pursuits and time for family activities were the most important reasons for change. The reasons for selecting a different specialty varied. This study's findings suggest that a student's likelihood of making an inappropriate specialty choice may be reduced by a broad undergraduate medical education with realistic experiences in clinical activity. Students' lack of awareness of the lifestyle of a particular specialty may be a significant factor in the flow of physicians from noncontrollable lifestyle specialty areas. Those who counsel medical students need to be aware of the increasing importance of controllable lifestyle features, changing attitudes, faculty role-modeling, and mentors as strong influences on students' choices of specialties. PMID- 1750956 TI - A review of the validity and accuracy of self-assessments in health professions training. AB - Valid self-assessment is fundamental to continuing professional competence but is seldom explicitly taught in health professions training. This review analyzed 18 scholarly articles published between January 1970 and February 1990 (14 articles regarding health professions trainees, and four concerning college students or graduate trainees) in which it was possible to compare performance as self assessed by trainees with performance as assessed by experts or objective tests. The validity of self-assessed performance was found to be low to moderate and did not improve with time in conventional health professions training programs. Self assessed performance seemed closely related to generalized self-attributions and was minimally influenced by external feedback in the form of test scores, grades, or faculty assessments. In five programs emphasizing explicit self-assessment goals and training strategies, moderate-to-high validity outcomes or improvements over time were demonstrated. Much of what passes for self-assessment in training seems the exercise of an underdeveloped skill, but effective training to improve validity and accuracy is available and feasible. PMID- 1750957 TI - Attitudes and factors affecting the decisions of men and women pediatrics residents toward having children during their residencies. AB - This study examines attitudes and factors affecting the decisions of pediatrics residents of both sexes toward having children during their residencies. In 1987, the authors surveyed by mail all 742 pediatricians who had trained at eight university-based residencies from 1981 to 1987; 417 responded. Of these, the men were significantly more likely than the women to have had children during their residencies (p less than .001). At the time of their residencies, 265 of these pediatricians were married. Of those who were married but did not have children during their residencies (175), the women were significantly more likely than the men to believe that having a child during residency would have had a negative influence on their careers (p less than .001) and would have been associated with difficulties in arranging child care (p less than .001). By contrast, among those pediatricians who were married and did have children during their residencies (90), their perceptions concerning the impacts on their careers of having children and the difficulty in arranging child care did not differ significantly by gender. The authors suggest that programs might explore the possibilities of greater flexibility in scheduling and of making child care more available so that residents could more easily combine their careers with having children. PMID- 1750958 TI - The student-initiated, faculty-assisted system of evaluation of clinical teaching at the University of Virginia. AB - The University of Virginia School of Medicine has developed a student-initiated, faculty-assisted system to evaluate the faculty who teach the third-year clinical clerkships. All students complete an evaluation at the end of each clerkship, and the fourth-year class and student government compile the results and publish a detailed annual report of the data, offering constructive criticism and recommendations for change. Teaching faculty then review the report and respond to the student government, the faculty clerkship committee, and the student curriculum committee, addressing the contents of the report and initiating proposals to correct deficiencies and improve teaching. The experience of the first two administrations of this system (1988-1990) has been encouraging, and the authors suggest that the system will be applicable to the evaluation of clinical teaching on a universal basis. PMID- 1750959 TI - A collaborative approach to a primary care preclinical preceptorship for underserved settings. AB - This study describes the first few years of a collaborative effort undertaken by the University of Washington School of Medicine (UWSM), the Washington-Alaska Montana-Idaho (WAMI) Area Health Education Center program, the Washington Academy of Family Practice, and the Family Health Foundation of Washington to provide students with an early introduction to primary care practice in rural and urban underserved settings. Starting in 1988, these collaborators organized a summer preceptorship that offered placements in the WAMI region to 23 student volunteers who were between their first and second years at the UWSM in 1989 and to 51 such students in 1990. A preliminary evaluation of the program indicated that the students (73 of whom participated in the evaluation) were extremely satisfied with the program's ability to provide them with firsthand exposure to community medicine. In conclusion, the authors discuss the advantages of collaboration and make suggestions for identifying potential educational partners. PMID- 1750960 TI - Retraining faculty for the problem-based curriculum at the University of Hawaii, 1989-1991. AB - The problem-based learning (PBL) curriculum, adopted by an increasing number of medical schools, requires retraining faculty for new roles as tutors with small groups of medical students. This study describes the procedures and results of four PBL training workshops (1989-1991) given at the University of Hawaii John A. Burns School of Medicine. Eighty-eight faculty volunteers each answered a 20-item multiple-choice questionnaire testing their knowledge of PBL both before and after they participated in a workshop. The posttest results were used to identify deficiencies in the tutors' knowledge and practice of both their role and their function. The authors conclude that these deficiencies, now identified, will be addressed in a systematic fashion in subsequent workshops. PMID- 1750961 TI - Behavior-change strategies used by a sample of physicians for patients at risk of coronary problems. PMID- 1750962 TI - Practitioners' ability to predict the educational value of their patients. PMID- 1750963 TI - [Croup and air pollutants: results of a two-year prospective longitudinal study]. AB - The Reutlingen/Tubingen/Rottenburg region in Baden-Wurttemberg is characterized by medium and small sized towns and rural areas. In 1986/87 875 cases of croup were registered there by the treating physicians during a 24-months period. In consideration of meteorological and virological "disturbing variables" the influence of the measured air pollution by SO2, NO, NO2, CO, ozone and dust on croup frequency was computed by means of statistical regression methods. For the months September till March, the main manifestation period of croup, weak but statistically significant influences of the daily means of NO and NO2 were found, for the whole year influences of NO, NO2, and CO. During the winter months temperature correlates positively and velocity of wind negatively, both statistically with significance, to croup frequency. The essential conditions of croup are individual and familiar disposition on the one hand, virus infections on the other. Air pollution of a concentration like given in the investigated region was found to be a weak additional factor that favours the manifestation of croup. PMID- 1750964 TI - A note on the comparative efficacy of three selective media for isolation of Campylobacter species from environmental samples. AB - The efficacy of three selective broths and agars, i.e. Preston-, mCCD- and CAR medium, were compared to each other in various combinations. Twelve Campylobacter coli and 9 Campylobacter jejuni strains that had been isolated from sewage were used as test strains. To evaluate the applicability for highly contaminated environmental samples 15 sewage samples were examined, subsequently. Significant differences between the media could not be ascertained. The application of Preston broth/agar or CAR broth/Preston agar, however, is strongly recommended for investigation of highly contaminated environmental samples, as bacterial overgrowth (CAR agar) and difficult retrievability from agar surfaces (mCCD agar) were observed. A necessity of blood-supplementation is assumed. PMID- 1750965 TI - [Detection methods and occurrence of Cryptosporidium sp. in selected surface waters]. AB - Cryptosporidium, a small coccidian parasite, is accepted as an important cause of severe diarrheal illness in man and animals; in immunocompromised persons illness may be life-threatening. Cryptosporidium is transmitted by oocysts, passed in the faeces. These oocysts are remarkable resistant to common disinfectants and they can survive for several months. Person-to-person, animal-to-person and faecal contaminations of the environment are proven routes of transmission. Also waterborne disease outbreaks caused by Cryptosporidium are well documented. This paper represents a modification of a method for the detection of Cryptosporidium in water, developed by Musial et al. and Rose et al. The method includes steps for filtration, elution, centrifugation, flotation and microscopic detection of Cryptosporidium oocysts in sediments using an indirect immunofluorescence technique and a native contrast-technique. With this modified method efficiency of recovery ranged from 8.1% to 27.1%. In addition, selected surface waters in Northrhine-Westphalia were examined. The finding of Cryptosporidium oocysts in 7 of 9 water samples (78%) demonstrates the occurrence of Cryptosporidium oocysts in surface waters in Western-Germany. These results suggest that more detailed studies are needed to assess the risk of this new pathogen in water, especially in removal and disinfection in water treatment plants. PMID- 1750966 TI - Evaluation of an enzymatic method for fast identification of Listeria spp. in cheese and meat products. AB - Listeria-Tek ELISA was compared with conventional cultural procedure of FIL/IDF (Federation International de Laiterie/International Dairy Federation) modified by us. The ELISA assay is able to detect Listeria innocua, Listeria monocytogenes, Listeria murrayi and Listeria welshimeri, after 48 h in artificially contaminated cheeses. No specific reactions, no false positive or negative were detected and the assay has a high correlation with the conventional method used in this research. We also analyzed meat products and cheeses and identified Listeria spp. and Listeria monocytogenes serotypes. In 313 food samples examined there were only 3 false positives. With ELISA Kit we obtained 0.9% more than with the cultural method and the percentage of false positives is 1.6%. So in commercial products the total absence of false negatives demonstrates the great sensitivity of the method in respect to investigated microorganisms. As determined by cultures 218 samples contained 47 Listeriae monocytogenes, 67 Listeriae innocua, 21 Listeriae welshimeri, 7 Listeriae ivanovii, 3 Listeriae murrayi and 3 Listeriae denitrificans. Listeria monocytogenens includes serotypes 1 (13) and serotypes 4 (14). 20 Listeriae monocytogenes were serotyped by polyantisera Difco (Detroit, Michigan). PMID- 1750967 TI - [Laboratory studies of Salmonella decontamination in bone meal using propionic acid]. AB - Laboratory investigations centered on determining the concentration and time of influence of propionic acid to decontaminate salmonella in bone meal as well as on the inhibitory effect of reanimation and recontamination. Tests have been conducted by means of contaminated bone meal charges either naturally or artificially stressed. Findings revealed, that freedom of salmonella could be achieved ranging between one hour and 21 days when adding 3% of propionic acid to the bone meal dependent on the stress of salmonella. Evidence could be proved to the inhibitory effect of reanimation of propionic acid at least one week after the entry of action. Protection of the bone meal treated with 3% of propionic acid against new contamination of salmonella has proved to be independent of the rate of recontamination. Freedom of salmonella lasting for two or three weeks could be stated after a holding time of one day. PMID- 1750968 TI - Occurrence of mycobacteria in drinking water samples. AB - 33 ground water samples from three drinking water treatment plants and 72 samples from domestic drinking water distribution systems were studied for the occurrence of mycobacteria. 86 out of these samples tested positive for mycobacteria with concentrations generally ranging between 10(2) and 10(3) cfu/l. In one distribution system up to 4.5 x 10(5) cfu/l were found. Species identified by biochemical reactions and by thin layer chromatography of mycolic acids included: Mycobacterium gordonae (most water samples), M. flavescens, M. kansasii, M. chelonae (domestic water systems) and M. fortuitum (drinking water treatment plant). Most isolates did not show patterns of biochemical reactivity attributable to any known mycobacterial species. PMID- 1750969 TI - Microorganisms in water, soil and air. Abstracts of papers presented at the Workshop of the Deutsche Gesellschaft fur Hygiene and Mikrobiologie, Section Hygiene and Public Health, Berlin, 14.-15.3. 1991. PMID- 1750971 TI - Use of a nutrition information system. PMID- 1750970 TI - [Guidelines for the testing and evaluation of skin disinfectants]. PMID- 1750972 TI - Use and misuse of dietary recommendations to evaluate food intake. PMID- 1750973 TI - Analysis of the sugar flow in Norway. PMID- 1750974 TI - Proposed system for food and nutrition surveillance in Norway. PMID- 1750976 TI - Grouping foods: uses of FAO food balance sheet database. PMID- 1750975 TI - Nutrition information systems and data quality requirements. PMID- 1750977 TI - A review of household budget surveys in 17 countries. PMID- 1750978 TI - Health impact monitoring. PMID- 1750979 TI - Food balance sheets. PMID- 1750980 TI - Household budget surveys. PMID- 1750981 TI - Dietary surveys and the use of the results. PMID- 1750982 TI - Problems and pitfalls of foot-to-nutrient conversion. PMID- 1750983 TI - Database requirements for calculations from food balance sheet data and household budget surveys. PMID- 1750984 TI - Comparison of dietary data from different sources: some examples. PMID- 1750985 TI - [Profession and market]. PMID- 1750986 TI - [Indications for home care--hot potato or logical development?]. PMID- 1750987 TI - [Indications for home care--it works this way!]. PMID- 1750988 TI - [The Free University Hospital in Amsterdam--looks to the future]. PMID- 1750989 TI - [Quality of the intake interview in district nursing]. PMID- 1750990 TI - [Nutrition of the bedridden patient. Care to measure and care for well-being]. PMID- 1750991 TI - [How competent do nurses want to be? The Law BIG/art. 55a (Professions in Individual Health Care)]. PMID- 1750992 TI - [Certification of competence]. PMID- 1750994 TI - [Nursing science and nursing care. The other side of one's own right]. PMID- 1750993 TI - [Land of courses]. PMID- 1750995 TI - [Exploring in the land of research. Experiences of the district nurse]. PMID- 1750996 TI - [Provincial Hospital Santpoort--from the dunes to the city]. PMID- 1750997 TI - [Developments in the labor market (1). Demand and supply till the year 2000]. PMID- 1750998 TI - [Nutrition in chronic loss of kidney function. Never able to just eat something that's nice...]. PMID- 1750999 TI - [Demonstration Nursing 1992 shaping up]. PMID- 1751000 TI - [Part-time education nursing science--1987 to the present]. PMID- 1751001 TI - [Training first-grade instructors in nursing. A new course]. PMID- 1751002 TI - The human cerebro-cerebellar system: its computing, cognitive, and language skills. AB - In this review of the human cerebro-cerebellar system, the focus is on the possible contributions of the cerebellum to cognitive and language functions. The role of the cerebellum in these human functions has tended to be obscured by the traditional preoccupation with the motor functions of the cerebellum, which have been widely observed in other vertebrates as well. In the human brain, some phylogenetically new parts evolved and enlarged in the cerebellum, concomitantly with the enlargement of association areas in the cerebral cortex. Anatomical evidence and behavioral evidence combine to suggest that this enlarged cerebellum contributes not only to motor function but also to some sensory, cognitive, linguistic, and emotional aspects of behavior. The anatomical evidence derives from the modularity of the cerebellum, whose cortical nerve cells are organized into longitudinal micro-modules, which are arrayed perpendicular to the cortical surface and parallel to each other. The number of these micro-modules increased when the cerebellum enlarged, which enlarged the computing capabilities of the network. (From principles underlying the processing of information, it is known that when modules with modest processing capabilities are assembled in large numbers in parallel, the resulting network can achieve remarkably powerful computing capabilities.) Such cerebellar computing capabilities can be utilized in the different areas of the cerebral cortex to which the cerebellum sends signals. The cerebellar output connections convey signals through the thalamus to the cerebral cortex in segregated channels of communication, which preserve the modularity of the cerebellum. Through these channels, modules in the lateral cerebellum can send signals to new cognitive and language areas of the cerebral cortex, such as Broca's area in the prefrontal cortex. The anatomy of the human cerebro-cerebellar system therefore suggests that the cerebellum can contribute to the learning not only of motor skills but also of some cognitive and language skills. Supporting this anatomical evidence is the mounting behavioral evidence, obtained both in normal brains and in clinical studies, which indicates that the lateral cerebellum is indeed involved in some cognitive and language functions. PMID- 1751003 TI - Effects of monocular deprivation on the visual fields of squirrel monkeys. AB - Five squirrel monkeys were monocularly deprived at birth for 3 years. Visual field testing for the deprived eye revealed no responses to visual stimuli at any position, including the monocular segment. These results are similar to those obtained in macaque monkeys after long-term neonatal monocular deprivation and indicate that lack of patterned visual input to an eye during development in primates can produce functional blindness throughout the visual field. Because the monocular segment of the visual field was not spared, binocular competition cannot be the only mechanism underlying this loss. Instead, lack of patterned visual input probably causes improper neuronal connections during development in all segments of the visual cortex resulting in complete loss of form vision. PMID- 1751004 TI - Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice. AB - The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions. In contrast to control mice, they failed to improve their performance from the first to the last session. Nevertheless, when later required to repeatedly learn the same discrimination over several days (repetitive testing), animals with ACC lesions no longer exhibited any learning deficit. The converse pattern of results was found in mice with PCC lesions. These animals performed much more poorly than control animals during the acquisition and first reversal of the discrimination, but displayed remarkable improvement over the subsequent four reversal sessions, gradually overcoming their initial impairment. However, when later submitted to repetitive testing, these animals again showed a substantial learning deficit. Neither ACC nor PCC cingulate lesions significantly affected the animals' retention capacities as measured by single test-trials over a 24-h interval. Yet, mice with PCC lesions were retarded in reversal learning after a long intersession interval (10 days), indicating that PCC, but not ACC, lesions did interfere with some long-term retention processes. These results imply that the ACC, as a part of the medial frontal cortex, may play a crucial role in temporally ordering a series of spatial responses, whereas the PCC seems to contribute to the formation and retention of each individual spatial response, probably by transmitting information from limbic structures such as the anterior thalamus and hippocampal formation to posterior neocortical association areas. PMID- 1751005 TI - Zona incerta lesions: effects on copulation, partner-preference and other socio sexual behaviors. AB - Sexually active males prefer a sexually receptive female to a non-receptive female, and partner-preference tests provide one way of studying the effect of brain damage on sexual motivation. Male rats with bilateral electrolytic lesions of the caudal zona incerta do not mate, and we studied the effects of zona incerta destruction on copulation and partner-preference. Lesioned males did not mate but were not indifferent to sexually receptive females. They continued to show a strong preference for a sexually receptive female over a non-receptive female. In addition, lesioned males showed many incomplete mounts i.e. mounts not accompanied by the pelvic thrusting necessary for intromission and ejaculation. Anogenital investigation of the receptive female was common. Taken together, these facts suggest that zona incerta destruction eliminates copulation without affecting sexual motivation, and that the failure to mate after lesioning probably reflects an inability to properly engage the locomotor responses of copulation. PMID- 1751006 TI - Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats. AB - Rats with radiofrequency lesions of the fimbria/fornix, or neurotoxic lesions of the mammillary bodies or the anterior thalamic nuclei were tested on their ability to perform a delayed non-matching-to-position task that had been learnt before surgery. In this task rats had to respond to a sample lever in an operant chamber and, after a variable delay (during which they were required to respond at the magazine tray), press the other lever when both were presented. Extensive mammillary body lesions had no effect on performance. In contrast, lesions in either the anterior thalamic nuclei or the fimbria/fornix produced marked deficits, the pattern of these deficits being consistent with a mnemonic impairment. It is argued that the anterior thalamic nuclei represent an important hippocampal output for spatial problems, but that the mammillary bodies are only necessary for certain types of mnemonic task. PMID- 1751007 TI - The effects of posterior cortical lesions on responses to visual threats in the Mongolian gerbil (Meriones unguiculatus). AB - Mongolian gerbils received aspiration lesions of either primary visual cortex (PVC), medial extrastriate visual cortex, retrosplenial cortex (RSC), or sham operations. The responses of gerbils to the presentation of an overhead visual stimulus were recorded in an open field. In all groups, presentation of the stimulus produced an increase in rearing. This suggests that the stimulus was detected by all animals. Gerbils with RSC or PVC lesions showed reduced levels of response to the stimulus. We suggest that some of the observed deficits can be explained as failures to produce responses to threat that are appropriate to the context in which the the threat was presented. PMID- 1751008 TI - Interactions between amygdaloid and hypothalamic self-stimulation: a re examination. AB - The function relating bar-pressing rate to the frequency of cathodal pulses was obtained in rats self-stimulating with amygdaloid (AMY) and lateral hypothalamic (LH) electrodes. The maximum self-stimulation (SS) rates in the AMY was found to be very low, compared to the LH. Concurrent stimulation with pairs of AMY-LH pulses did not shift the rate-frequency functional laterally, indicating the absence of summation of the two rewarding effects. In a second experiment, concurrent AMY-LH stimulation (using sub-threshold intensity LH pulses) facilitated bar-pressing for AMY stimulation (it increased the slope of the AMY rate-frequency function) without shifting this function laterally. In a third experiment, subjects were given a choice between a pulse frequency yielding maximal AMY rate and a series of higher pulse frequencies. Subjects consistently preferred the higher frequency values, attesting that the maximum AMY rates were not constrained by a saturating reinforcing effect. In a fourth experiment, subjects were given a choice between AMY stimulation and concurrent AMY-LH stimulation, using low intensity LH pulses. Subjects showed no preference for either stimulation condition, although rates were higher for the latter condition. These findings suggest that the maximum rate for AMY stimulation was constrained by factors interfering with bar-pressing and that the effect of these factors was attenuated by co-activation of the LH. In a fifth experiment, pre treatment with phenobarbital mimicked the rate-enhancing effect of concurrent AMY LH stimulation for 2 of the 4 subjects tested. This finding suggests that the LH pulses contributed to attenuate seizure activity accompanying AMY SS. In a final experiment, AMY SS rates were also increased by co-activation of rewarding sites in the rostral MFB but not the dorsal raphe, suggesting an anatomical specificity of this effect. PMID- 1751009 TI - Motor effects of globus pallidus stimulation in the rat: lesions to corticofugal fibers block the motor effects. AB - Unilateral electrical stimulation of the globus pallidus (GP) in anesthetized male rats was used to determine the nature of the activity driven in muscles of the neck and shoulder by GP output. In 6 groups of animals stimulation was coupled with lesions to sites that interrupted corticofugal fibers or GP output. Interruption of corticofugal fibers blocked the driven activity while lesions that compromised GP output left the activity unaffected. PMID- 1751010 TI - Activity of spinal trigeminal pars oralis and adjacent reticular formation units during differential conditioning of the rabbit nictitating membrane response. AB - Spinal trigeminal nucleus pars oralis (SpoV) is anatomically linked to brain circuitry thought to subserve unconditioned and conditioned nictitating membrane responses in rabbit. Single-unit recording from SpoV and adjacent reticular formation obtained during conditioning from awake, behaving animals revealed modulation of unit firing related to CS, US, and CR occurrence. SpoV participates directly in the unconditioned response and probably relays US information to other brain areas subserving conditioning. The presence of CR-related activity suggests that SpoV may participate in the CR motor output pathway, and may also provide CR-related information to cerebellum. Sensory convergence and CR-related activity in reticular formation mark this structure as a candidate locus of primary neuronal plasticity in this example of conditioning. PMID- 1751011 TI - Control of food delivery in food-deprived rats mediates analgesia. AB - An experiment was carried out to investigate the effects of control of food delivery, in food-deprived rats, on analgesia. Tail flick latency was used as an index of pain sensitivity and naloxone reversibility of analgesia was used as the criterion for opioid involvement. Food-deprived rats were submitted to one of two schedules of food delivery. The 'contingent' group could control the delivery of food by lever-pressing. The 'non-contingent' group received the same number of food pellets but delivery of food was independent of lever-pressing behaviour. Animals in the 'control' group were placed in the test chamber but did not receive any pellets. Subjects were tested on 6 consecutive days, each test session being of 10 min duration. Half of the animals in each group received an intraperitoneal injection of saline (0.5 ml) prior to each test session, the other half received an intraperitoneal injection of naloxone (5 mg/kg in 0.5 ml saline) prior to each session. Both contingent and non-contingent food delivery resulted in a significant post-test analgesia. The analgesia was noticeably greater when food delivery was non-contingent and this analgesia was reversible by naloxone. The findings suggest that non-contingent food delivery, in food deprived rats, elicits an opioid analgesia, whilst contingent food delivery elicits a non-opioid analgesia. PMID- 1751012 TI - Inhibitory effects of powerline-frequency (60-Hz) magnetic fields on pentylenetetrazol-induced seizures and mortality in rats. AB - The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45 75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed. PMID- 1751013 TI - Anti-muscarinic drug effects in a swim-to-platform test: dose-response relations. AB - Rats were given subcutaneous or intraperitoneal injections of scopolamine, intraperitoneal injections of atropine, or control injections, and trained on a simple swim-to-platform task. Errors were proportional to dose for both drugs over a wide range. No difference was found in the effects of intraperitoneal or subcutaneous scopolamine but scopolamine was 25 times more potent than atropine. The potency of both drugs in impairing swim-to-platform behavior was similar to their potency in abolishing the cholinergic component of neocortical low voltage fast activity. The electrocortical effect of anticholinergic drugs may be a major factor in the behavioral impairment they produce. PMID- 1751014 TI - Brightness-discrimination learning in cats is influenced by early visual deprivation. AB - A two-choice apparatus for food reward was used. Normal and visually deprived cats were trained to discriminate white and black cards. After the animals had reached criterion, the contrast difference between the cards was diminished in steps. When the brightness ratio had been reduced to 1.8, discrimination was impaired in the deprived cats and not in the normally raised cats. PMID- 1751015 TI - Clinical course of spontaneous gangliothalamic hemorrhage in the acute period- who requires surgical removal? AB - We analyzed the clinical courses of 93 consecutive patients with gangliothalmic hemorrhage for the first three weeks after the ictus and investigated the factors affecting the clinical course and the final outcome. The clinical status was assessed daily using the Glasgow Coma Score (GCS) and patients were divided into two groups according to the clinical course; Group I included those who improved and Group II consisted of patients who deteriorated. There were 44 patients (47.3%) in Group I and 49 patients (52.7%) in group II. Each group was subdivided into the conservative group and the surgical group. In Group I only eight patients (18.2%) received surgery while twenty-five patients (51.0%) received surgery in Group II. Clinical features and computed tomography characteristics of these four groups were compared. Our results suggested that the surgery is rarely required for patients 1) whose GCS values are 12 or more without deterioration; 2) with hematomas smaller than 3 cm in diameter or 20 ml in volume; 3) with midline shifts of less than 3 mm, and 4) whose subtypes of the hematomas are P1, P2a, T1, T2a, and T2b. For proper comparison of the results of medical and surgical treatment, the patient population should include the patients 1) who became deteriorated progressively regardless of initial GCS values; 2) whose GCS values are below 12; 3) with hematomas larger than at least 3cm in diameter or 20ml in volume; 4) with midline shift of more than 3mm, and 5) whose subtypes of the hematoma are P2b or GT. PMID- 1751016 TI - Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity. AB - Non-acetylated salicylates have been recommended for use as alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) in aspirin and/or tartrazine sensitive patients. We experienced a case of an aspirin-sensitive asthmatic patient who developed a broncho-obstructive reaction after taking 100 mg of sodium salicylate. The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients. PMID- 1751017 TI - Surgical treatment of giant cavernous hemangiomas of the liver--analysis of 7 patients. AB - Seven patients with giant cavernous hemangioma of the liver were treated surgically with success at Pusan Gospel Hospital, Kosin Medical College, Pusan, from 1980 through 1989. They were 3 males and 4 females, and their ages ranged from 6 to 59 years. The tumors were located on the right lobe of the liver in 5 patients and on the left lobe in 2. The lesions were solitary in all patients, and their sizes varied from 4cm to 15cm in diameter. All patients underwent hepatic resection: 1 right hepatic lobectomy and 4 partial resections for tumors on the right lobe, and 1 left lobectomy and 1 left lateral segmentectomy for tumors on the left lobe. There was no surgical death, but 1 patient had a postoperative complication: multiple stress ulcers on the stomach and ileum. The pathologic diagnosis was cavernous hemangioma in all cases. In the long-term follow-up, there was no recurrence of preoperative symptoms in any patient. PMID- 1751018 TI - A survival study of surgically treated lung cancer in Korea. Lung Cancer Surgical Study Group. AB - Survival rate over a 5-year period were studied in a series of 658 proven primary lung cancer patients treated by thoracic surgeons at 8 institutes during the period from 1976 to 1987 in Korea. The study was designed as a multi-center cooperative work for the statistical analysis of the followup result. Clinical data of age, sex, morbidity, and staging of the tumor were assessed in 540 patients to evaluate their 5-year survival rates. Eventually, 405 resectable patients were analyzed by stage, cell type, surgical procedure, and TNM status. The 5-year actuarial survival rates by stage in the resectable group were: stage I 39.7%, II 30.6% III A 16.3%, III B 6.7%, and IV 0%. The 5-year survival rates by cell type were: squamous cell 31.9%, adenocarcinoma 21.2%, large cell 11%, and small cell 6%. The survival rates by surgical procedures were: lobectomy 30.7% and pneumonectomy 25.7%. The survival rates by TNM status in the operable group were: T1 34.7%, T2 26.8%, T3 7.5%, T4 5%; N1 23%, N2 10%, N3 3%; MO 21%, and M1 0%, respectively. The overall actuarial 5-year survival rate in the group of 405 resectable patients was 25.9%. PMID- 1751019 TI - Effect of ursodeoxycholic acid on experimental hepatic porphyria induced by griseofulvin. AB - Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries. PMID- 1751020 TI - Solitary myeloma with massive extracellular crystalline structures--a case report. AB - We describe a case of solitary myeloma showing cystic change filled with massive crystalline structures in a 54-year-old woman. A bone X-ray showed a solitary cystic osteolytic lesion in the right iliac bone. Serum and urine protein electrophoresis showed no demonstrable M-protein, and bone-marrow aspirates did not show any myeloma cells. Histologic examination of the tumor revealed aggregation of plasma cells with massive extracellular infiltration of the rhomboid-shaped crystalline structures. In immunoperoxidase staining, both these crystalline structures and the cytoplasms of the myeloma cells demonstrated a positive reaction for lambda light chain. By electron microscope, the large extracellular crystalline structures were observed, and we found unique rhomboid or rectangular-shaped crystalline structures in the cytoplasms of the myeloma cells. PMID- 1751021 TI - Body stalk anomaly--a case report. AB - A case is presented of an amnionic rupture sequence which led to massive fetal ventral herniation and lordoscoliosis. Characteristic ultrasonographic findings of an omphalocele, fetal attachment to the placenta, and the absence of free floating umbilical cord were observed. PMID- 1751022 TI - High jejunal obstruction as a sequela of necrotizing enterocolitis. AB - A case of high jejunal obstruction due to stricture is reported. It is a rare form of late sequelae of neonatal necrotizing enterocolitis(NEC). Barium contrast study of the small bowel is recommended for earlier diagnosis and treatment before discharge from the hospital, even is an asympto-matic patient. PMID- 1751023 TI - Arteriovenous malformation of the uterus--a cause of massive operative bleeding. AB - Arteriovenous malformations of the uterus are extremely rare and they occur either in congenital or acquired forms. The most common clinical presentation is abnormal uterine bleeding, which may be aggravated by therapeutic curettage. Because of their rare incidence and clinical importance in management of patients, we report a case of arteriovenous malformation causing serious bleeding during a hysterectomy for uterine leiomyoma. The patient was a 47-year-old multiparous woman who had a history of chronic vaginal bleeding for one year. Numerous anomalous blood vessels draining into the right and left uterine arteries were found on the anterior wall of the uterus and parametrium. PMID- 1751024 TI - Alternating dissociated nystagmus with palatal myoclonus--a case report. AB - An extraordinary eye movement was seen in a vegetative patient. His eyeballs were exotropic in the primary position and showed dissociated nystagmus which appeared alternately in each eye every few seconds. He also had palatal myoclonus quite asynchronous with the nystagmus. To our knowledge, there has been no such nystagmus documented in the literature. We report the new nystagmus with his EOG and brain MRI. PMID- 1751025 TI - A 23187-stimulated calcium uptake and GABA release by cerebrocortical synaptosomes: effects of high pressure. AB - Guinea pig cerebrocortical synaptosome preparations were used to study the effect of compression to 62 ATA on 45Ca2+ uptake and [3H]GABA release using a calcium ionophore A 23187, which bypasses the voltage-sensitive calcium channel. Pressure was found to exert a suppressive effect on the A 23187-induced release of [3H]GABA, while having no significant effect on A 23187-stimulated 45Ca2+ uptake. On the other hand, both depolarization-induced 45Ca2+ uptake and [3H]GABA release were inhibited by pressure exposure. These results suggest that pressure may suppress GABA release by affecting pre-synaptic events subsequent to calcium influx. PMID- 1751026 TI - The effect of (+)- and (-)-oxaprotiline administered repeatedly on the dopamine system. AB - The behavioural and biochemical effects of repeated (14 and 28 days) treatment with (+)-oxaprotiline (a noradrenaline uptake inhibitor) and (-)-oxaprotiline (levoprotiline, without influence on noradrenaline uptake; the clinically active antidepressant) were studied in rats. Both those enantiomers given repeatedly increased the locomotor and exploratory activity and reduced the immobility time in Porsolt's test. The D-amphetamine-induced locomotor hyperactivity, as well as the stereotypies induced by D-amphetamine and apomorphine, were increased by the oxaprotilines. Single-dose treatment with both the oxaprotilines was not effective in the tests mentioned above. Repeated (+)-oxaprotiline administration reduced the binding (Bmax but not KD) to dopamine D-1 receptors in the striatum and limbic system; levoprotiline was inactive. The binding to dopamine D-2 receptors was not changed by either drug. Both the enantiomers showed only low affinity for brain dopamine D-1 and D-2 receptors in vitro. The obtained results indicate that chronic treatment with (+)- and (-)-oxaprotiline increases behavioural responsiveness of the dopamine mesolimbic and striatal systems. PMID- 1751027 TI - Brain kinetics of L-[beta-11C]dopa in humans studied by positron emission tomography. AB - The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11C in the beta position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L [11C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[11C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[11C]DOPA utilization as reference. Total uptake of L-[11C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[11C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood brain barrier. Benserazide 0.5 mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[11C]DOPA. Thus, 11C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[18F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis. PMID- 1751028 TI - The presence of glutathione in primary neuronal and astroglial cultures from rat cerebral cortex and brain stem. AB - The concentration of the tripeptide glutathione (GSH) was measured in primary cultures of neurons and astroglial cells from rat cerebral cortex and brain stem. The concentration of GSH was found to be approximately 20 nmol/mg protein in the neuronal culture from the cerebral cortex and ca. 40 nmol/mg protein in the neuronal brain stem cultures. A GSH concentration of approximately 20 nmol/mg was observed in the astrocyte cultures from both brain regions. The possibility to increase the GSH concentration was tested by incubating the cultures in the presence of the GSH precursor gamma-glutamylcysteine (gamma-GC). In the cultured astrocytes gamma-GC produced a dose-dependent increase in GSH. A similar increase was observed in the neuronal cultures, but this effect failed to reach statistical significance. PMID- 1751029 TI - Facilitating effect of amphetamine on the response of rabbit aortic strips to adrenaline, dopamine and serotonin. AB - Amphetamine increased the response of rabbit aortic strips to adrenaline, dopamine and serotonin at consistently lower doses than those exerting a direct contracting effect. The amphetamine-facilitated contraction had the same shape as that produced by biogenic amines alone, whereas the contraction produced by amphetamine alone was more delayed and flatter. Serotonin and dopamine facilitated each other, but less markedly and with a narrower interval between facilitating and contracting doses than amphetamine. Pargyline exerted no facilitating effect on biogenic amines. Phentolamine and prazosin inhibited the direct response to adrenaline, dopamine and amphetamine, and the amphetamine facilitated response to adrenaline and dopamine; they were inactive against serotonin alone and combined with a facilitating dose of amphetamine or dopamine. Cyproheptadine inhibited the direct response to serotonin and amphetamine, and the amphetamine-facilitated response to serotonin; it was inactive against dopamine and adrenaline both alone and combined with a facilitating dose of amphetamine or serotonin. PMID- 1751030 TI - Buspirone does not produce a 5-HT1A-mediated decrease in temperature in man. AB - Buspirone, a putative serotonin (5-HT)1A partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT1A receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT1A partial agonists which have been reported to produce hypothermia by a 5-HT1A-mediated mechanism. PMID- 1751031 TI - (-)-Deprenyl can induce soluble superoxide dismutase in rat striata. AB - (-)-Deprenyl (0.25 or 2 mg/kg) or saline was injected daily into male Wistar rats for 3 weeks. The striata were dissected out and soluble and particulate superoxide dismutase activity measured. (-)-Deprenyl at 2 mg/kg induced a significant increase in the soluble but not the particulate form of the enzyme. The possibility that this action contributes to the ability of (-)-deprenyl to retard nigral degeneration in man and prolong life in rats is discussed. PMID- 1751032 TI - Developmental expression of cathepsin L and c-rasHa in the mouse placenta. AB - An investigation is described of the expression of the cysteine proteinase cathepsin L during placental development. In addition, whether cathepsin L expression is linked to c-rasHa expression in development, as it is in metastatic cells, is examined. Large amounts of cathepsin L and its transcript are present in the mouse placenta, more than six times more than in adult kidney and liver. Throughout gestation, cathepsin L and its transcript are located in the giant cells and spongiotrophoblasts of the placenta. Several forms of different mobility on denaturing gels are found in the placenta. Their apparent molecular weights, as determined from the gels, are 43,000, 39,000, 29,000, and 20,000. The 39-kDa form is procathepsin L. The 29-kDa and 20-kDa forms are lysosomal cathepsin Ls. The 39-kDa procathepsin L and the 20-kDa mature cathepsin L are the most abundant species in the placenta and are present in about equal amounts throughout gestation. At any time during gestation, placental minces synthesize and secrete only procathepsin L. The amniotic fluid of the fetus contains the 43 kDa form of cathepsin L and procathepsin L, but no detectable amounts of mature cathepsin L. By contrast, serum from nonpregnant or pregnant mice contains three forms of cathepsin L (i.e., the 43-kDa form, procathepsin L, and mature cathepsin L). Cathepsin L and the rasHa oncogene are expressed in two coincident waves corresponding to periods during which the placenta is invasive and just before parturition. The presence of large amounts of cathepsin L in the placenta suggests that the proteinase has a significant function there. Expression of cathepsin L in the placenta is potentially under the control of the ras gene product p21; both are under developmental control. PMID- 1751033 TI - Sequence requirements for embryonic transcriptional activation of a gastrula specific actin gene in Xenopus laevis. AB - Cytoskeletal actin genes undergo developmentally timed transcriptional activation at the gastrula stage of embryonic development in the amphibian Xenopus laevis. To study the regulation of this process, a molecularly marked cloned actin gene has been introduced into living embryos by microinjection, and levels of its transcripts (which are distinct from endogenous actin message) have been measured by RNase protection. In vitro mutagenesis of the marked gene, followed by microinjection and transcriptional analysis of various mutants, has been used to search for gene sequences that participate in accurate transcriptional initiation and developmental control. Deletion mutants containing only 90 nucleotides of upstream sequence undergo correct developmental regulation, while deletion to -33 prevents normal activation of the gene. In the presence of sufficient upstream sequence, an actin-globin fusion gene, containing only 564 nucleotides downstream of the actin gene transcription startsite, is correctly activated. Taken together, these results imply that all sequences necessary for correct temporal regulation reside between -90 and +564 nucleotides, with respect to the transcriptional start site of the actin gene. They further suggest that developmental activation of actin gene transcription may involve either (1) interaction of non-DNA binding proteins with basal transcription factors, or (2) the concerted action of ubiquitous promoter-binding factors and factors that interact with downstream regulatory regions. PMID- 1751034 TI - Efficient transfection of chicken cells by lipofection, and introduction of transfected blastodermal cells into the embryo. AB - Chicken blastodermal cells (CBCs) and primary chicken fibroblasts (PCFs) have been lipofected with a variety of lacZ constructs encoding Escherichia coli beta galactosidase (beta-gal). A reporter construct (phspPTlacZpA) containing a mouse heat-shock protein 68 gene (hsp 68) promoter was used to establish conditions for efficient lipofection. The construct, in circular or linear plasmid form or as reporter sequences alone, was transferred efficiently by incubating the cells for 3.5 h in a mixture of 6.2 micrograms Lipofectin (a cationic liposome preparation from Bethesda Research Laboratories) and 1.55-3.1 micrograms DNA per mL DMEM. These lipofection conditions were used to transfer a reporter construct (pCBcMtlacZ) containing a Zn(2+)-inducible chicken metallothionein (cMt) promoter, and constructs showing constitutive expression due to Rous sarcoma virus plus chicken beta-actin (pmiwZ) or cytomegalovirus (pMaori3) promoters. Endogenous chicken beta-gal and transferred bacterial beta-gal activity could be distinguished clearly by incubating the cells with the substrate, Xgal, at pH 4.3 or 7.4, respectively. Expression of phspPTlacZpA in chicken cells did not appear to require specific induction of the mouse hsp68 promoter, whereas expression of pCBcMtlacZ required treatment of the cells for 6-12 h with 150 microM ZnCl2. Bacterial beta-gal activity was observed following lipofection of CBCs that were cultured in suspension or plated. The efficiency of lipofection was at least 1 in 25 for CBCs, judging by the proportion of cells shown to have beta-gal activity 16-24 h after lipofection treatment began; these events could represent transient or stable incorporation of the construct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751035 TI - Production of transgenic mice from cryopreserved fertilized ova. AB - Cryopreserved fertilized mouse ova were used to generate transgenic mice via micromanipulation. Five-DNA constructions were injected into a total of 1,052 cryopreserved ova, of which 683 (65%) survived the injection and were transferred into recipients. Of 35 recipients, 66% became pregnant and littered a total of 88 pups. As controls, these DNA constructions were also injected into 1,123 fresh ova, of which 744 (66%) survived and were transferred. Of 42 recipients, 79% became pregnant and littered a total of 167 pups. That is, 22% of fresh ova that were transferred developed into live pups, whereas only 13% of cryopreserved ova did so. Of the pups born, 42 of the 167 (25%) produced from fresh ova were transgenic, and 28 of the 88 (32%) produced from cryopreserved ova were transgenic. In terms of the injected ova that had been transferred, 5.6% of the 744 fresh and 4.1% of the 683 frozen ova developed into transgenic mice. These data indicate that the efficiency of production of transgenic mice from cryopreserved ova is close to that from fresh ova. That observation and the fact that cryopreserved ova allow more efficient utilization of animals suggest that cryopreserved ova can be used instead of fresh ova to produce transgenic mice. PMID- 1751036 TI - Growth and DNA replication in rabbit blastocysts. AB - DNA content and DNA polymerase activity were measured on rabbit blastocysts removed from the uterus at 24-hr intervals over the period of days 4-7 postcoitum (pc). Median DNA content increased 53 times over the 72-hr period, from 25.3 ng on day 4 to 1,360 ng on day 7. Median DNA polymerase activity (fmole of radiolabeled nucleotide incorporated in 30 min at 37 degrees C) increased 393 fold from day 4 to day 7: 32.8 to 12,900. These embryos also increased in surface area and volume by 334-fold and 6,078-fold, respectively. Litters containing individuals with high DNA content also tended to have similar individuals with high DNA polymerase activity. Therefore, DNA polymerase activity may be a useful measure of the potential for the next cell division. A large amount of variation existed between blastocysts in all parameters measured. An analysis of variance, conducted to partition variation between litters and within litters, determined that within-litter variation was actually greater than that between litters, resulting in intraclass correlation coefficients less than 0.5. There was also a positive regression of DNA content and DNA polymerase activity on surface area in 6- and 7-day-old blastocysts after eliminating variation attributable to litters. The developmental pattern of DNA polymerase activity in the rabbit may be quantitatively different from that described in the mouse. The pattern in mammals is very different from that described in several nonmammalian species. PMID- 1751037 TI - Effects of maturation and co-culture treatments on the developmental capacity of early bovine embryos. AB - A total of 901 cumulus-oocyte complexes (COCs) were collected from bovine ovaries obtained at a local abattoir. COCs randomly assigned to Treatment I (n = 451), were cultured in TCM-199 + 10% fetal bovine serum (FBS) and hormones, while oocytes in Treatment II (n = 450) were cultured in TCM-199 + 20% estrous cow serum (ECS). Assessment of maturation revealed that 91.3% (42/46) of oocytes in Treatment I had reached metaphase II of meiosis, which was greater (P less than 0.05) than the 73.3% (33/45) in Treatment II. Following in vitro fertilization, 203 oocytes from Treatment I were co-cultured on bovine granulosa cells (Treatment IA) while the remaining 202 oocytes were co-cultured on bovine oviductal cells (Treatment IB). Similarly, 203 oocytes from Treatment II were co cultured on granulosa cells (Treatment IIA) or oviductal cells (Treatment IIB, n = 202). Co-culture was maintained for 8 days. The proportion of cleaved zygotes was higher (P less than 0.05) in Treatment IB (86.6%) compared to Treatments IA (78.8%), IIA (58.1%), and IIB (64.8%). The proportion of cleaved zygotes that progressed beyond the 16-cell stage was also greater (P less than 0.001) in Treatment IB (71.4%) compared to Treatments IA (50.0%), IIA (35.4%) and IIB (55.8%). Treatment IB also produced the highest proportion of blastocysts (P less than 0.0001) (41.1%) versus 24.6% (IA), 11.3% (IIA) and 18.3% (IIB). The proportion of day 6 morulae that progressed to form day 8 blastocysts was similar for both co-culture treatments (IA, 70.1%; IB 70.2%; IIA, 51.5%; IIB 50.8%) and varied only between in vitro maturation groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751038 TI - Enhancement of acrosome reaction and subzonal insemination of a single spermatozoon in mouse eggs. AB - The acrosome reaction in mouse spermatozoa was induced by various means. These were 1) varying incubation time in T6 medium, 2) incubation in T6 medium with added A23187, 3) incubation in T6 medium with added dbcGMP and imidazole, 4) exposure to an electric field, and 5) a combination of incubation in a medium with dbcGMP and imidazole and electroporation. The mean percentages of acrosome free spermatozoa obtained by these various methods and assessed on the basis of both Bryan's stain and immunolocalization by FITC-labeled monoclonal antibodies increased by steps from 36% to 67%, 73%, 86%, and 92%. Individual spermatozoa from the various treatments were afterwards microinjected under the zona pellucida of a mouse oocyte. The fertilization rate for eggs microinjected with a spermatozoon treated with A23187, dbcGMP, and imidazole, by electroporation and by a combination of the last two methods also increased by steps from 17% to 34%, 36%, and 70%, respectively. Ninety-five percent of the fertilized oocytes reached the early blastocyst stage, thirty-eight percent of these blastocysts implanted in pseudopregnant mice, and twenty-eight percent developed to term. These results indicated the varying degrees of success of different ways of inducing acrosomal loss in spermatozoa and their subsequent success rates in fertilization and further in vitro and in vivo development. PMID- 1751039 TI - Sperm selection capacity of the human zona pellucida. AB - Previous hemizona assay (HZA) results have illustrated a positive and significant correlation between the percentage of morphologically normal spermatozoa in the semen and the number of spermatozoa tightly bound to the zona pellucida. The present study was designed to evaluate the morphologic features using strict criteria of spermatozoa tightly bound to the zona pellucida. Semen samples of 4 normozoospermic and 11 teratozoospermic men were used to compare the percentage of normal spermatozoa in the semen with that found 1) after swim-up separation and 2) bound to the zona under HZA conditions. The mean (+/- SEM) % normal forms for normozoospermic men in semen, after swim-up and zona-bound spermatozoa were 21.5 +/- 1.6, 27.5 +/- 2.9, and 44.8 +/- 3.4, respectively. A significantly higher % of normal forms were found among zona-bound sperm compared to swim-up forms (p = 0.02) and seminal sperm (p = 0.02). The mean % of normal sperm forms present in semen, after swim-up and zona pellucida-binding for teratozoospermic men, were 3.7 +/- 0.9, 5.8 +/- 1.6 and 15.6 +/- 3.1, respectively. Significant differences existed between the % of normal sperm forms found in the swim-up and zona-bound spermatozoa (P = less than 0.01 and P = less than 0.0003, respectively) compared to the original ejaculates. Results indicate that a selective process against abnormal spermatozoa occurs at the site of the zona pellucida.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751040 TI - Cytochemical evidence of an organized microtubular cytoskeleton in Xenopus laevis oocytes: involvement in the segregation of mitochondrial populations. AB - An organized microtubular cytoskeleton was discovered in the cytoplasm of Xenopus laevis oocytes. The microtubules were observed in 10- to 30-micron cryostat sections by indirect immunoperoxidase labeling using an antibody to tubulin. A gradual extraction of cells with a nonionic detergent was essential for good penetration of the antibody into the cells. In the cytoplasm of all previtellogenic oocytes, a dense network of criss-crossed long microtubules was associated in a basket-like structure surrounding the mitochondrial mass. At the beginning of vitellogenesis, the network meshes enlarged, while clusters of mitochondria migrated, in close association with microtubule bundles. At the beginning of vitellogenesis, the reorganization of the microtubular network, mostly in the vegetal hemisphere, occurred during the segregation of the mitochondrial populations. Reorganization is characterized by (1) a temporary enlargement of the network and close association of mitochondrial clusters with microtubular bundles, and (2) a progressive organization of a ring-shaped microtubular structure in the crown elaboration area. It is hypothesized that these modifications of the microtubular cytoskeleton contribute to the maintenance of cell shape and the polarized organization of the cell. PMID- 1751041 TI - Equine oocyte in vitro maturation: influences of sera, time, and hormones. AB - Objectives of the present research were to determine the influences of types of media, sera, time and hormones on equine oocyte in vitro maturation (IVM). The following types of media and sera were evaluated: Menezo's B2 medium (B2), modified Tissue Culture Medium 199 (TCM), Defined Medium (DM), fetal calf serum (FCS), mare serum collected on the first day of estrus (MS), and mare serum collected on the day of ovulation (MSO). Resultant oocyte maturation was compared with the control: DM with bovine serum albumin (BSA). Effect of culture time (0, 15, and 32 hr) and the following hormones on oocyte IVM were evaluated: none, bovine luteinizing hormone (bLH; 1, 10, 100 micrograms/ml), equine luteinizing hormone (eLH; 100 micrograms/ml), bovine follicle-stimulating hormone (FSH; 5 micrograms/ml), and equine chorionic gonadotropin (eCG; 1 and 100 IU/ml). Cumulus expansion in the media and sera experiments was 50% (DM with BSA), 80% (TCM, B2, and DM with MS or MSO), and 100% (FCS with any medium). The proportion of metaphase II (MII) oocytes was significantly (P less than 0.05) increased the percentage of MII oocytes as compared with 0 hr of culture. Cumulus expansion in the hormone experiments was 80% (none, bLH, and eLH), and 100% (eCG and FSH). Freshly prepared bLH significantly (P less than 0.05) inhibited nuclear maturation of equine oocytes. In summary, 15 hr of culture was sufficient time for equine oocyte IVM and all combinations of medium, serum, and hormone addition were equally effective in achieving IVM except fresh bLH and DM with BSA. PMID- 1751042 TI - Distribution of filamentous actin in and around spermatids and in spermatozoa of Australian conilurine rodents. AB - The distribution of filamentous actin around the maturing sperm head and in spermatozoa of four species of Australian conilurine rodents was investigated at the light and electron microscopic levels. Similar results were obtained for all the species studied. Mechanically isolated spermatids had NBD-phallacidin positive longitudinal bands of fluorescence over the dorsolateral surface and, in late spermatids, bands of bright fluorescence passed perpendicularly from the dorsal convex to ventral concave surface. TEM observations indicated that these regions corresponded to filaments of ectoplasmic specializations and granular filamentous material around the tubulobulbar complexes, respectively. In testicular and cauda spermatozoa NBD-phallacidin fluorescent material was present in the two ventral processes that extended from the upper concave surface of the sperm head; also fainter material occurred along the concave border and as a dorsocaudal spur. Its distribution was identical for testicular and cauda spermatozoa. TEM of late spermatids showed that in the ventral process closest to the apical hook there were between 170 and 245 filaments, which attached to the inner surface of the postacrosomal dense lamina; in the more caudal ventral process about 70 filaments occurred. No filaments were, however, visible in the mature spermatozoon but, after immunocytochemical labelling for actin, deposition of gold particles was evident over ventral processes of both late spermatids and cauda spermatozoa. Within the female tract these ventral processes made contact with the zona matrix and were taken into the egg cytoplasm unchanged in morphology. The possible functional significance of the filamentous actin in these structures is discussed. PMID- 1751043 TI - Improvement of fertilizing performance by normal and abnormal mouse semen after zona opening of mature oocytes. AB - The usefulness of opening the zona pellucida by partial zona dissection (PZD) to enhance fertilization of mature mouse oocytes was studied after insemination with three types of semen: normal and diluted semen and semen from long-term vasectomized males. Zona opening did not by itself induce parthenogenetic cleavage of mature oocytes and did not significantly increase mono- and polyspermic fertilization of oocytes inseminated with normal semen. While a fertilization rate of 62% was obtained among intact oocytes, of which 4.5% were polyspermic, a 66.8% fertilization rate was observed among PZD oocytes, 6.3% of which were polyspermic. However, after using diluted semen, only 54 of 193 intact oocytes were fertilized (28%), and PZD improved the fertilization rate to 65.4%. Cleavage rate of nonmanipulated oocytes inseminated with abnormal semen from vasectomized males was dramatically decreased in comparison with those inseminated with normal semen (7.6% vs. 65%). PZD induced a moderate but significant improvement of fertilization performance when using this abnormal semen (19.6%). PMID- 1751044 TI - Time course and pattern of cortical granule breakdown in hamster eggs after sperm fusion. AB - We have determined the temporal relationship between sperm fusion and cortical granule breakdown in the hamster egg. Sperm fusion was determined by the Hoechst transfer method (Stewart-Savage and Bavister: Dev Biol 128:150-157, 1988), and cortical granules were visualized with fluorescein isothiocynate-conjugated Lens culinaris agglutinin (Cherr et al. J Exp Zool 246:81-93, 1988). By 55 min after insemination, there was an 85% reduction in the density of cortical granules (fewer than four granules/100 microns2). Taking this value as the completion of the cortical reaction, analysis of the data indicate that the cortical reaction was completed 9 min after sperm fusion and 3 min after the formation of the zona and cell surface blocks to polyspermy. There was no obvious spatial pattern of granule loss in eggs that had a Hoechst-positive sperm but had not completed the cortical reaction. PMID- 1751045 TI - Detection of a soluble acrosome reaction-inducing factor, different from serum albumin, associated with the ovulated egg-cumulus complex. AB - Soluble extracts of the ovulated hamster egg-cumulus complex (ECC) were tested on capacitated sperm for activity in inducing the physiological acrosome reaction (AR). Evidence for occurrence of the physiological AR included enhanced sperm penetration of intact homologous zonae pellucidae as well as induction of AR in nonattached and in zona-bound sperm following a brief coincubation with test compound. Since hamster serum albumin, a major protein of hamster body fluids, also induces spontaneous ARs under certain conditions, it was used as one of the comparators for the acrosome reaction inducing factor (ARIF; Westrick et al., Biol Reprod 32 [Suppl 1]. 213, 1985) activity in the ECC. Sperm exposure to concentrations of the soluble ECC extract ranging from 0.04 to 0.2 mg protein/ml significantly increased penetration of salt-stored zonae by 36%, mean numbers of penetrating sperm by 90%, ARs in nonattached sperm by 65%, and ARs in zona-bound sperm by 102%. Hamster serum albumin added after completion of capacitation had no significant effect on these parameters. We conclude that 1) the ovulated ECC contains a soluble ARIF that augments zona-induced ARs and sperm penetration and 2) the ARIF is not serum albumin. PMID- 1751046 TI - [Retrograde cardioplegia and reperfusion in patients with multiple lesions of the coronary arteries]. PMID- 1751047 TI - [Surgical tactics in occlusive lesions of the brachiocephalic and coronary arteries]. AB - Surgical management of combined arterial occlusions is a difficult problem. Combined lesions of the coronary arteries and brachiocephalic trunk are marked by significant mutual aggravation. The authors examined 48 patients with this pathological condition in the last 4 years, 32 of them underwent restorative surgical interventions. The direct effect was positive in 87% of patients. Four patients died after the operation. Comparative evaluation of the late-term results was carried out by the actuarial method. The authors believe a stage-by stage character of the intervention to be expedient, except for cases of one stage critical ischemia carried out simultaneously in two arterial channels and the possibility of simultaneous reconstruction of the sternotomy approach. PMID- 1751048 TI - [Plastic correction of aortic stenosis in two- and three heart valve diseases]. AB - Plastic correction of aortic stenosis with simultaneous intervention on the mitral and, in some cases, on the tricuspid valve was performed on 50 patients whose ages ranged from 25 to 53 years (average age 43.2 years); 15 were in NYHA functional class III and 35 in class IV. There were 38 females and 12 males. Correction of the aortic stenosis was achieved by open valvulotomy and additional plane resection of the cusps, suture plastic was conducted whenever necessary. In 6 cases calcinates were removed form the cusps simultaneously. Mitral valve prosthetics was undertaken in 42 patients, and open mitral commissurotomy in 8 patients. In 17 patients aortic and mitral stenoses were attended by defect of the tricuspid valve which called for plastic correction. Among the 50 patients who underwent operation 8 (16.0%) died. there were no fatal outcomes among patients related to the NYHA functional class III. In 41 cases the result of aortic stenosis correction was satisfactory, which was confirmed by clinical and echocardiographic data. After the operation, opening of the aortic valve cusps during echocardiography in the M-regimen increased, on average, from 12 +/- 2.0 to 18 +/- 2.6 mm. According to doppler-echocardiogram, the gradient on the aortic valve reduced, on average, from 45 +/- 5.0 to 26.5 +/- 4.0 mm. Only in one female patient aortic incompetence started progressing after the operation and called for prosthetics 6 months later. PMID- 1751049 TI - [Inter-arterial anastomosis in dextral position of the aortic arch in patients with tetralogy of Fallot]. AB - The article discusses the results of formation of inter-arterial anastomoses in 58 (12.7%) patients with a severe form of Fallot's tetralogy in dextra-position of the arch of the aorta. The specific features of the course and diagnosis of dextra-position of the aortic arch in Fallot's tetralogy are analysed, and the significance of radiologic and echocardiographic examination in the choice of the position and type of interarterial anastomoses is determined. It is proved that Blalock-Taussig's anastomoses must be formed on the side opposite to the aortic arch, while shunting operations must be carried out on the side on which the arch of the aorta is located. PMID- 1751050 TI - [A physiological method of annuloplasty of the mitral valve]. AB - The work deals with an anatomo-functional substantiation of plastic repair of the mitral valve. Isolated annuloplasty was carried out in 20 patients with mitral incompetence, annuloplasty with aortic prosthetics was conducted in 13 patients. The method allows a prosthesis with a larger diameter to be used in the last named group of patients. A fatal outcome which was not connected with the operative method was encountered in 2 cases. The clinical and hemodynamic effect was good in all patients. PMID- 1751051 TI - [Various aspects of surgical treatment of vasorenal hypertension]. AB - The results of examination and treatment by surgery of 103 patients with vasorenal hypertension are analysed. Retromboses and restenoses of the reconstructed renal arteries and grafts and uncorrected hyperaldosteronism were the most frequent causes of the poor results. Adequate reconstruction of the renal arteries leads to correction of hyperaldosteronism in patients with normal or high activity of plasma renin. Low-renin secondary hyperaldosteronism in patients with vasorenal hypertension is an indication for simultaneous correction. PMID- 1751052 TI - [Late results of mitral valve replacement with ball-type and low-profile prostheses]. AB - The discussion covers long-term results of mitral valve replacement with Soviet made prostheses. Two hundred and sixty-three patients have been under observation, the follow-up periods lasting from six months to five years. A ball valve prosthesis (MK4-25) was implanted to 125 patients; 138 patients received a low-profile (,) prosthesis. Functional parameters were improved in 86 (69.9 percent) patients with ball-valve implants and in 118 (89 percent) patients with low-profile implants. Ten ball valve implanted patients (8 percent) and 6 (4.3 percent) patients with low-profile prostheses died in the long-term period. The five-year survival of rotation-disc artificial valve recipients was 90 percent, and that of the ball valve-implanted patients, 83 percent. PMID- 1751053 TI - [Criteria of the operability of patients with a common arterial trunk based on hemodynamic data]. AB - Criteria of operability of patients with a common arterial trunk were evaluated from a complex of hemodynamic, clinical, and morphological data. The patients were divided into 2 main groups according to the value of the pulmonary blood flow (PBF): group 1 with the pulmonary to systemic blood flow ratio (PBF/SBF) greater than 1; group 2 with PBF/SBF less than 1. The indications for operation in group 1 depended on the degree of PBF increase. For instance, an operation was indicated for patients with marked increase of PBF (PBF/SBF greater than 2); in cases with moderate PBF growth [formula: see text] the indications for operation were determined only after additional lung biopsy. The operation was not indicated for group 2 patients (PBF/SBF less than 1.0) because of the severity of their condition due to obstructive pulmonary vascular disease. PMID- 1751054 TI - [Detection of cardiac insufficiency by computer-assisted monitoring of the response of intra-cardiac hemodynamics to exercise test in patients with ischemic heart disease with similar lesions of the coronary arteries (patient selection for the aortocoronary bypass)]. AB - Preoperative identification of cardiac insufficiency in patients with ischemic heart disease (IHD) has proved essential for the success of surgery on the coronary arteries. To provide for an objective assessment of the contractile function of the myocardium in selecting candidates for surgery among IHD patients with over 70-percent narrowing of one, two, and three coronary arteries, use was made of the central hemodynamics indices in response to the loading test during right heart catheterization with computer-assisted monitoring and mathematical analysis. Two patient groups were distinguished during the hemodynamic loading test: group I showing a high and effective chronotropic reserve (+X) and group II presenting a negative chronotropic reserve (-X). It was established that with equal numbers of narrowed coronary arteries and similar clinical manifestations, the estimates of myocardial contraction may differ which determines indications for surgery and preoperative care. PMID- 1751055 TI - [Morphological changes in patent ductus arteriosus after endovascular occlusion (clinico-experimental study)]. AB - The work is based on a comparison of data gained in experiments with the results of clinical examination of a large group of patients in the late-term period after endovascular occlusion of a patent ductus arteriosus (PDA). The regular features of the course of the morphological process in the zone of the PDA after implantation of a botallo-occluder into it were studied. Clinico-morphological parallels were made. The high efficacy and reliability of the new method of endovascular treatment of PDA, developed at the Moscow Second Medical institute, was substantiated morphologically and confirmed clinically. PMID- 1751056 TI - [Diagnosis and treatment of expiratory stenosis of the trachea and main bronchi in children]. AB - The results of examination and the course of expiratory stenosis were studied in 15 children, 3 of them suffered from bronchomalacia of the left main bronchus. Bronchoscopy and poly-positional radioscopy with contrast study of the trachea and the large bronchi are the principal diagnostic methods in this disease. Sclerosing therapy was carried out in III degree expiratory stenosis. Two patients with bronchomalacia of the main bronchus and cystic lung hypoplasia underwent pulmonectomy with treatment of the main bronchus at the site of its branching off from the tracheal bifurcation. The results of sclerosing therapy and operations were good. PMID- 1751057 TI - [Pulmonary hypertension and the possibilities of its radiographically guided endovascular correction in chronic nonspecific lung diseases]. AB - Bronchial arteriography and catheterization of the pulmonary artery (PA) were applied in the examination of 120 patients with chronic nonspecific diseases of the lungs. The specific features of bronchopulmonary blood circulation in various pathological processes were revealed. Pulmonary hypertension (PH) was encountered in 71.5% of cases, and pressure in the PA was significantly higher in the group of patients with massive bronchopulmonary blood shunting (chronic pulmonary suppurations) than in the group of patients with minimal blood shunting (nonsuppurative processes). Radiologically-guided endovascular correction of the disorders of the bronchopulmonary blood flow was conducted in 85 patients by occlusion of the bronchial arteries (BA). Pressure in the PA significantly reduced after the correction due to diminished left-to-right blood shunting. Thus, besides the generally known mechanisms, bronchopulmonary shunting of blood plays a certain role in the pathogenesis of PH in chronic suppurative processes. Endovascular BA occlusion for correction of PH in patients with bilateral lesions is expedient. PMID- 1751058 TI - [Surgical tactics in complicated pulmonary echinococcosis]. AB - The authors analyse treatment of 326 patients with hydatid disease of the lungs. Complications were found in 112 (34.3%) of them. Broncho-fibroscopy was included in the complex of therapeutic measures in rupture of the cyst into the bronchus, and pleural puncture, therapeutico-diagnostic thoracoscopy and drainage of the pleural cavity in rupture into the pleural cavity. Temporary occlusion of the draining bronchus with Fogarty's catheter was conducted to prevent intraoperative aspiration complications. If organ-preserving operations are indicated, preference is given to A. A. Vishnevsky's echinococcectomy with a laser scalpel since the Delbet's method is fraught with the danger of cutting of the sutures due to acute inflammatory changes of the wall with the formation of a residual cavity or an abscess of the lung. A differentiated approach to preoperative management and the choice of the operative techniques reduced the incidence of postoperative complications and reduced mortality in complicated hydatid disease of the lungs to 0.9%. PMID- 1751059 TI - [Repeated anti-reflux operations]. AB - The authors had under observation 73 patients who underwent various antireflux operations with poor results, 68 of them were subjected to repeated interventions, fundoplication in most cases. The causes of failure of primary and repeated antireflux operations are analysed, the indications for and the techniques of reconstructive interventions are discussed. It is emphasized that patients with hiatal hernia and reflux esophagitis must be concentrated in specialized medical institutions. PMID- 1751060 TI - [Non-pharmacological treatment of arrhythmia using the method of trans-catheter ablation]. AB - Trans-catheteral ablation is an important therapeutic method for nonpharmacological management of various types of cardiac arrhythmias. Since its introduction into clinical practice in 1982, it has proved its efficacy in disturbance or change of the type of atrioventricular conduction and conduction along accessory abnormal atrioventricular conduction pathways. Positive results have also been attained in the treatment of some patients with ventricular tachycardia. The energy sources used for ablation include direct current pulses possessing large energy, high-frequency currents, and laser energy. Ablation with direct current and high-frequency current is already used successfully in patients, while the use of laser energy for ablation of myocardial arrhythmogenic tissue is limited mainly to operations on the open heart. The use of alternating high-frequency current has attracted particular attention in the last years. Trans-coronary chemical ablation is another recently introduced method which is not connected with the use of electric current. Only experimental and a small clinical experience with this new method has been gained to date. This survey systemasizes the current knowledge of the biophysical bases of the various method of ablation from the standpoint of the mechanisms of treatment, the methodology and the main types of tissue response. Clinical experience with trans-catheteral treatment of cardiac arrhythmias is analysed. PMID- 1751061 TI - [Calcinosis of the pulmonary valve in trilogy of Fallot]. PMID- 1751062 TI - [Recurrence factors in benign gastric ulcer]. AB - Among 7015 upper gastrointestinal endoscopies done during five consecutive years (1984-1988) 642 patients were diagnosed as having benign gastric ulcer. Of this group, 213 patients have been followed-up during an adequate period of time. A recurrence was diagnosed endoscopically in 43 (20.18%). The authors analyze the influence on recurrences of general factors (age, sex, alcohol, tobacco and drugs), family history and local factors (site and size of the ulcer, histological lesions, concomitant duodenal ulcer or single or multiple ulcers). The conclusions are that in females and in males over 60 years of age, NSAIDS are the factors which greatly influence recurrences, while in males under 60 years of age, excessive smoking and alcohol. Chronic gastritis and intestinal metaplasia are common in recurrent ulcers. Multiple ulcers as well as those associated with duodenal ulcers have a greater tendency to recur. Recurring ulcers are more common at the incisura angularis. Recurrences are usually located at the site of a previous ulcer. PMID- 1751063 TI - [The extraintestinal manifestations of Crohn's disease: our experience]. AB - During a period of sixteen years we have treated 120 patients with Crohn's disease, 41 of them with extraintestinal lesions besides of it's main intestinal pathology. These patients represented the 34.1% of all attended in this service. We describe the clinical and epidemiological aspects and the incidence of extraintestinal manifestations of the disease. Joint manifestations were prominent (90.2%), followed by cutaneous-mucosal lesions (47.8%) and cholelithiasis (24.3%). Urinary symptoms secondary to fistula or invasion from the adjoining inflammatory process came in fourth place. Other rare localizations are described. The literature is reviewed. PMID- 1751064 TI - [Experimental acute pancreatitis in the rat. The quantification of pancreatic necrosis after the retrograde ductal injection of sodium taurocholate]. AB - Acute haemorrhagic pancreatitis was induced in rats by injecting 5% sodium taurocholate into the common biliopancreatic duct. The condition was associated with an increase in the serum amylase levels as well as progressive pancreatic necrosis resulting in 100% mortality before 36 hours. This experimental model was documented by quantifying nine different parameters of pancreatic necrosis and giving more information about the induced lesion. The extent of pancreatic necrosis was evaluated at different intervals, 5.77% at 12 hours, 14.9% at 24 hours, and the rats died before 36 hours of pancreatitis induction with an average percentual necrosis of 29.9%. This model seems suitable for more pathogenic as well as therapeutic studies on acute pancreatitis in the rat. PMID- 1751065 TI - [Klatskin's tumor. The current status 25 years later]. PMID- 1751066 TI - [Sarcoidosis of the tongue. Apropos a case]. AB - Here we present the case of a patient with lesion on the tongue, during more than 6 months, which in its self required different therapeutic measures and because of a benign evolution is remitted to this center for study, which concluded with an histological diagnosis of sarcoidosis, a granulomatous disease systemic in character which in this patient only affect the tongue which reminds us daily the necessity to remember this entity by internist, gastroenterologists and dentists. PMID- 1751067 TI - [Acute abdomen due to eosinophilic gastroenteritis. A study of 2 cases]. AB - Report of two cases of eosinophilic gastroenteritis. In both cases the presentation was an acute abdomen syndrome. The etiological diagnosis was postoperative, because in the preoperative period there were no data characteristic of this entity. Probably this disease is more frequent than reported and although the treatment is medical, there are some cases in which surgery is justified. PMID- 1751068 TI - [Portal hypertension secondary to an arterioportal fistula. Treatment by embolization]. AB - We report a case of arterioportal fistula which was probably the result of percutaneous liver biopsy. Portal hypertension with hemorrhage by esophageal varices was the clinical presentation. We describe the features of the ultrasound, selective arteriography and Doppler ultrasound examination. The fistula was catheterized superselectively and successfully embolized with steel coils. PMID- 1751069 TI - [Acute pancreatitis associated with primary hyperparathyroidism]. AB - A case of acute pancreatitis associated with primary hyperparathyroidism is reported. There was none of usual causes of pancreatitis, which did not recur following the removal of a parathyroid adenoma. There are over one hundred of cases of acute or chronic pancreatitis associated with hyperparathyroidism in the literature, suggesting a causal relationship between the two entities. The pancreatic disease has been attributed either to the hypercalcemia or to the excess of circulating parathyroid hormone. However, some authors have recently questioned any link between these two diseases. PMID- 1751070 TI - [Gastric leiomyosarcoma. Apropos a case]. PMID- 1751071 TI - [Endoscopy units]. PMID- 1751072 TI - [The usefulness of a difference in the transmucosal potential in the functional evaluation of ileoanal reservoirs]. PMID- 1751073 TI - [A giant retroperitoneal cystic lymphangioma]. PMID- 1751074 TI - [Crohn's disease in Spain. Don Carlos Marina Fiol, 30 years ago]. PMID- 1751075 TI - ASAIO presidential address. AB - ASAIO has a proud heritage and a list of many accomplishments. It has given birth to many highly specialized societies and meetings. These changes and new developments in other fields have diverted it from being mainly a kidney society to being more multidisciplinary than ever before. Although meeting attendance declined for a number of years, the productivity of the society did not. Now attendance is increasing, and the number of submitted abstracts has exceeded all past records. Increasing activity in ASAIO may reflect the awareness of the need for a multidisciplinary meeting in this explosive era of artificial organ development. ASAIO can and should play a major role in fostering artificial organ research and development in the years to come. I am confident that it has the strengths to accomplish many important goals. I am very proud to have served as President of this society with a marvelous past and a promising future. PMID- 1751076 TI - Thrombin generation in cardiac device recipients. AB - Thrombin generation measured after LVAS (4 patients) and TAH (1 patient) implantation was found to be elevated (3 times normal) in the first postoperative week and declined to normal levels when anticoagulation was begun. Thrombin generation was not elevated at the times of thromboembolic events (TIAs; N = 4 episodes). PMID- 1751077 TI - Preliminary in vitro evaluation of the first neonatal total artificial heart. AB - A neonatal total artificial heart (TAH), used as a bridging device, can offer circulatory support for patients suffering from otherwise insupportable and inoperable congenital cardiac defects. The choice of the 7.0 ml stroke volume (SV) was based on reported studies on cardiac output (CO) requirements and maximum dimensions of a neonate size TAH. This SV will allow a bridging period of up to 10 weeks in the growing neonate. For in vitro testing purposes, "high profile" ball valves of in-house design (10-13 mm ID) were used. Redesign of the existing in vitro testing systems, including mock circulation and high-flow blood reservoirs, was required for the smaller device. Mock circulation studies (rates 90-160 BPM, full-fill and ejection modes) showed adequate device performance, with CO values well above the reported marginal output value of 139 ml/kg/min. PMID- 1751078 TI - K & T covariate with V in hemodialysis. As K increases and T decreases, V also decreases. AB - The authors varied urea clearance (K), dialysis time (T), and ultrafiltration (UF) in 294 hemodialyses on 23 patients and studied changes in urea space (V), determined by total dialysate urea removal. As K increased and UF and T decreased, V also decreased. K, T, and V, thus, covariate and dialysis adequacy, as studied by KT/V is not a simple function of three independent variables. Patients dialyzed quickly with little UF will need a higher KT/V than those dialyzed slowly with much UF. PMID- 1751079 TI - Kt/V: patients do not get what the physician prescribes. AB - Monthly urea kinetic modeling is performed [service Kt/V (urea)] to ensure that dialysis prescriptions provide patients a Kt/V greater than or equal to 1 and yield a protein catabolic rate (PCR) greater than or equal to 0.8. The frequency with which the dialysis prescription (physician's order +/- 5%, p +/- 5%) was achieved was calculated by three methods: 1) CompuMod (3 ureas; computer derived), 2) Jindal-Goldstein, and 3) Daugirdas, (2 and 3% reduction of urea). Ten patients were followed serially over 1 month for a total of 120 dialyses. Mean Kt/V values for each method were: prescription, 1.54 +/- 0.36; service, 1.40 +/- t0.63; CompuMod, 1.33 +/- 0.27; Jindal-Goldstein, 1.55 +/- 0.24; and Daugirdas, 1.33 +/- 0.23. The percentages of dialyses within the p +/- 5% were 12.4%, CompuMod; 12.8%, Jindal-Goldstein and 14.3%, Daugirdas. The percentages above p +/- 5% were 20.4%, CompuMod; 47%, Jindal-Goldstein; and 21.4%, Daugirdas. The percentages below p +/- 5% were 67.3%, CompuMod; 40.2%, Jindal-Goldstein; and 64.3%, Daugirdas. The CompuMod and Daugirdas methods of assessment of Kt/V were significantly lower (p less than 0.001) than the prescribed Kt/V, whereas the Jindal-Goldstein estimate was not. The authors conclude that dialysis patients rarely achieve their prescribed Kt/V. The service Kt/V, therefore, is not a useful parameter for prescribing dialysis therapy. The CompuMod and Daugirdas methods are the best estimates of the Kt/V, while the Jindal-Goldstein equation overestimates the Kt/V. The need for frequent urea kinetic modelling is stressed. An online urea monitor for each dialysis would be the ideal solution. PMID- 1751080 TI - The influence of dialysis membrane upon protein catabolic rate. AB - It has been hypothesized that the protein catabolic rate (PCR) is dependent upon the amount [Kt/V (urea)] and the type of dialysis (synthetic vs. cellulosic membrane). In an ongoing multicenter study comparing short hour-high flux with conventional cellulosic dialysis, 49 patients have completed 6 months and serial urea kinetic data has been obtained. Of the 49, 28 were on AN69S membrane dialyzers, and 21 on cellulosic. The patients on AN69S received significantly less Kt/V than those on cellulosic dialyzers (0.97 +/- 0.3 vs. 1.20 +/- 0.2; p = 0.0016), yet attained similar PCRs (1.07 +/- 0.2 vs. 1.02 +/- 0.1, NS). Significant (p = 0.002) linear relationships between PCR and Kt/V (urea) were found, yet the line slopes were higher for AN69S (average 0.46) than cellulose (average 0.25). Patients on AN69S achieve the same PCR for less Kt/V than patients on cellulosic dialyzers, supporting the hypothesis. PMID- 1751081 TI - Is Na+ modeling necessary in high flux dialysis? AB - One important pathogenic factor in dialysis hypotension is the drop in plasma osmolality. Increasing the dialysate Na+ concentration decreases hypotensive episodes. The authors studied 39 patients being treated with high flux dialysis. During a 9 week period, the patients were on a standard Na+ dialysate (Na+ = 140 meq/L) basal period (B); 9% (Na+ = 149 meq/L) linear (L); step drop (S); and exponential drop (E). The Na+ program was changed weekly at random. The results obtained with the three Na+ modeling programs were similar. We compared the periods with and without Na+ modeling: no differences were found in weight gained interdialysis, mean blood pressure predialysis and postdialysis, and hemoconcentration. Serum Na+ levels were significantly higher predialysis and postdialysis for those patients on Na+ modeling. Hypotensive episodes and cramps decreased 50% with Na+ modeling. The amount of hypertonic and normal saline given during dialysis was markedly reduced. Na+ modeling should always be used in patients being maintained on high flux dialysis. PMID- 1751082 TI - Comparison of conductivity measured hematocrit to microhematocrit. AB - Two electrical conductivity methods of hematocrit (H) measurement, Coulter Counter (CCH) and lonometer (IH), were compared to the microhematocrit (MH) with two different anticoagulants, Li Heparin (Li) and EDTA. The results showed MH-Li is higher than MH-EDTA (mean difference 1.7 vol%). The IH-Li is 1.8 vol% higher than CC H-EDTA. These differences are attributed to osmotic shrinking of red cells by EDTA. The MH-Li and IH-Li correlate very closely (r = .992), and are considered to provide the truest hematocrit values. PMID- 1751083 TI - Less symptomatic hypotension using blood volume controlled ultrafiltration. AB - Symptomatic hypotension due to ultrafiltration (UF) is one of the most frequent unwanted side effects of dialysis therapy. Using hemoglobinometry for continuous monitoring of blood volume (BV), ultrafiltration rate (UFR) can be adapted to actual changes in BV. A control system is shown in which UFR is set according to a predefined profile of BV. The conditions of control are: relative BV shall decrease steadily; BV shall decrease rapidly during the first 60 min of dialysis, thereafter decrease in BV should be less; UFR shall be as high as possible; and dry weight should be obtained within a given time. Application of this controlled UF method in 10 dialysis patients shows significantly fewer hypotensive periods and muscle cramps compared to conventionally constant UFR. It is concluded that BV controlled UF is an important step toward optimizing dialysis therapy. PMID- 1751084 TI - High venous urea concentrations in the opposite arm. A consequence of hemodialysis-induced compartment disequilibrium. AB - Resistance to urea diffusion among body fluid compartments diminishes the therapeutic effectiveness of hemodialysis. Cell membrane or capillary wall resistance is thought to be responsible for hemodialysis-induced urea disequilibrium. The authors examined the possibility that reduced blood flow might contribute to urea disequilibrium in the arm opposite the blood access site. Blood samples were taken simultaneously from a vein in the arm opposite the access site and from the arterial port after occluding the access graft between the needle sites for 1 min. Venous urea nitrogen levels from the opposite arm averaged 10% higher after 5 min, 26% higher after 60 min, and 36% higher after 120 min of dialysis. A three-compartment model of urea kinetics that includes a blood flow term accurately predicted all measured urea nitrogen concentrations in both arms. These data suggest that the opposite arm often behaves as a compartment with high resistance to urea diffusion. Slow diffusion from this compartment is partially due to reduced blood flow/compartment volume, and results in a delayed fall in venous blood urea nitrogen (BUN). PMID- 1751085 TI - The effect of surface hydrophilicity on biomaterial-leukocyte interactions. AB - Leukocyte adhesion onto a series of polyetherurethanes containing various ratios of polyethylene oxide (PEO) to polytetramethylene oxide (PTMO) in the soft segment was evaluated using an in vitro series shunt. The deposition of polymorphonuclear (PMN) and mononuclear (MN) leukocytes was measured quantitatively using labelling techniques. Results showed that H/H-1, the most hydrophobic surface, adsorbed higher amounts of PMN leukocytes. It was also observed that for most materials the number of PMN and MN leukocytes deposited reached a plateau within 15 minutes. Unlike MN adherence, the presence of plasma proteins increased the number of PMN leukocytes deposited on the materials. PMID- 1751086 TI - SPUU-PEO-heparin graft copolymer surfaces. Patency and platelet deposition in canine small diameter arterial grafts. AB - The influence of an SPUU-PEO-Heparin (B-PEO-HEP) copolymer coated blood contacting surface on patency and platelet deposition in small diameter (4 mm i.d.) Biomer grafts was investigated using a canine model. Grafts were implanted in the bilateral carotid and femoral arteries. B-PEO-HEP coated grafts still showed patency after 3 days. Control Biomer grafts occluded before 24 hr. (postoperatively). SEM of the luminal surfaces of the Biomer grafts demonstrated large amounts of adherent platelets with distorted morphologies, while B-PEO-HEP grafts did not. In platelet studies, B-PEO-HEP grafts showed significantly less platelet adhesion than Biomer grafts. The improved blood compatibility of B-PEO HEP graft co-polymer coatings attests to their usefulness for coating or casting. PMID- 1751087 TI - A physical model for the titanium-tissue interface. AB - X-ray photoelectron spectroscopy (XPS) was used to determine changes in titanium oxide composition, oxide stoichiometry, and adsorbed surface species as a function of exposure to model physiologic environments. The oxide on titanium became heterogeneous and polarized as a function of exposure. Changes included an increase in surface hydroxyl groups, and adsorption of H2PO4- and HPO4(2-). The heterogeneous nature of the surface led to preferential adsorption of lipoproteins, glycolipids, or both from serum. PMID- 1751088 TI - In vivo results of hydrogel composite pericardial substitutes. AB - In this study, two improved pericardial patches were developed and evaluated for their efficacy as pericardial substitutes. The patches are composites consisting of a hydrogel (PHEMA) that coats an underlying mesh (either ETFE or PET). Studies were conducted using subcutaneous implants in rats and pericardial patch implants in greyhound dogs. Adhesions between the substitute and pericardium and the epicardium were minimal. The ETFE composite patch caused an unacceptable epicardial reaction. The PET patch results were encouraging; the epicardium was largely unaffected by the patch. PMID- 1751089 TI - Measurement of peritoneal dialysate volume by CT. AB - Three-dimensional (3-D) graphic reconstruction of serial image data of x-ray CT on three dialysis patients was studied to measure peritoneal dialysate (PD) volume. Volume estimation with a surface reconstructed model provided a 16% error; a 35% error was found with a voxel model, although the total time required by the voxel model was 15 times less. PMID- 1751090 TI - Staphylococcus epidermidis biofilms: unexpected outcome of double and triple antibiotic combinations with rifampin. AB - Staphylococcus epidermidis, in contact with artificial surfaces, may produce a protective glue-like matrix or biofilm. The authors demonstrated that rifampin alone among 35 antibiotics penetrated the biofilm within a 24 hr exposure producing a major but incomplete killing. Antibiotics of the cell-wall active class (including vancomycin) were synergistic with rifampin, completing the bactericidal action. The addition of these antibiotics to a rifampin-vancomycin combination did not alter the synergy. Other antibiotics (including aminoglycosides) antagonized rifampin activity. This antagonism of rifampin was maintained when the antibiotics were added to the rifampin-vancomycin synergistic combination. These results may have implications for the choice of optimal therapeutic regimens in the management of implant-associated infection. PMID- 1751091 TI - Comparative rates of antibiotic action against Staphylococcus epidermidis biofilms. AB - The relative resistance of S. epidermidis implant-associated infections to antibiotic therapy has been ascribed to a protective function of the gluelike biofilm matrix produced by strains of S. epidermidis in contact with artificial surfaces. Using a standardized S. epidermidis biofilm assay we determined the periods of exposure required by various antibiotics to produce cessation of biofilm metabolic activity. Rifampin has the superior rate of action, producing substantial disruption of biofilm activity by 7 hr of exposure, but leading to replacement of the susceptible bacterial cells by rifampin-resistant mutant survivors. Other antibiotics required longer periods of exposure, in excess of 48 hr, but produced a bactericidal outcome. Combinations of antibiotics with rifampin produced strikingly divergent results. Cefazolin and vancomycin (cell wall active antibiotics) produced a bactericidal outcome at 16 hr of exposure, whereas gentamicin (aminoglycoside) neutralized the rapid action of rifampin with metabolic activity maintained at 48 hr. We confirmed the selectively protective function of the S. epidermidis biofilm with regard to antibiotic action. In vitro biofilm assays may be of value in guiding antibiotic therapy in S. epidermidis implant-associated infection. PMID- 1751092 TI - Optimization of pacing parameters for conditioned latissimus dorsi muscle in cardiomyoplasty. AB - Synchronous paced contractions of latissimus dorsi muscle pedicle (LDM) around the heart improve ventricular function in dynamic cardiomyoplasty. To optimize assistance and prolong pacemaker battery life, the LDM should be stimulated with the lowest energy pacing parameters (PP) that will produce maximal muscle contraction. Muscle fractional shortening (FS) and duration of contraction (CT) were studied in conditioned, fatigue-resistant LDM of six goats. Fractional shortening and CT were determined at increasing amplitude, (A, 1-6v); pulse width, (PW, 60-450 musec); and frequency, (F, 5-130 Hz). Maximal rate of contraction was determined by pacing at higher rates. Maximal FS plateaued after V, 2.4 +/- .6v; PW, 125 +/- 47 musec; and F, 36 +/- 9 Hz. Mean CT for all PP was significantly longer (p less than or equal to 0.001) than the burst length (185 msec). Increasing F resulted in CT, which peaked at 460 +/- 59 msec. Increasing rate of contraction demonstrated that over 87 beats per minute the muscle fails to achieve complete relaxation, and, therefore, maximal FS. PMID- 1751093 TI - Perineural leads and burst stimulation optimize contraction of skeletal muscle. AB - Electrode position and stimulation mode were hypothesized to be independent variables for the contractile response of skeletal muscle. Perineural and intramuscular electrodes were tested with single and burst pulse generators. Voltage requirements and muscle force generation were measured. Perineural leads improved the efficiency of stimulation for muscle contraction and yielded reduced threshold and plateau voltages compared to intramuscular leads. There were no differences between the different types of perineural leads. Burst stimulation had a wider range of voltage for muscle fiber recruitment and was confirmed to elicit greater maximal force than single stimulation. PMID- 1751094 TI - First significant animal survival with a Wankel-type left ventricular assist device. AB - The authors' laboratory is developing a device for heterotopic left ventricular assistance. It consists of a titanium Wankel-type rotary pump, driven by an hermetically sealed electric motor. In our animal experiments, the motor-pump unit was implanted in the thoracic wall. The pump was connected to the left heart chambers by left atrial cannulation, and to the descending aorta. The motor was connected to the power and control unit by an electric wire through the skin. In this report, the authors describe the first significant animal survival with this system. Laboratory results were encouraging for hemolysis. The pump failed at 13 days due to a deposit of fibrin and blood cells in the gear housing. This problem was not surprising since similar events have been encountered with centrifugal devices. However, further design improvements should allow longer animal survival and clinical application. PMID- 1751095 TI - Transesophageal echocardiography for the evaluation of mitral valve prostheses in the weanling sheep. AB - The sheep model has been widely accepted for evaluating the in vivo performance of artificial valves. Introduction of transthoracic echocardiography revolutionized the evaluation of human cardiac valves, but in many cases, resolution of transthoracic studies in sheep is inadequate. The authors used transesophageal echocardiography to follow the performance of chronically implanted mitral prostheses. The technique has proven feasible and safe, requiring sedation only and being done in the spontaneously breathing animal without endotracheal intubation in the left lateral position. The HP 77020A, equipped with a standard HP 5 mHz transesophageal transducer probe, is used. The authors have had to modify the probe to allow for automatic cooling. Standard insertion techniques are used and the probe is positioned in the stomach, close to the gastroesophageal junction. They were able to assess leaflet motion, vegetations, and calcification and use color flow doppler to evaluate stenosis and regurgitation. The technique is convenient and permits a complete assessment of valve function in 10 minutes. Reproducibility has been confirmed. Validation of quantitative data will require further study. PMID- 1751096 TI - Long-term anticalcification effect of Fe3+ in rat subdermal implants of glutaraldehyde preserved bovine pericardium. AB - Fe3+ preincubation has been shown to inhibit pathologic calcification of glutaraldehyde preserved bovine pericardium (GPBP) in the short-term rat subdermal model (21 days). This study was designed to test the long-term anticalcification efficacy of Fe3+ in the same model. Glutaraldehyde preserved bovine pericardium was preincubated (1 hr, 25 degrees C) in 0.1M FeCl3, 0.01M FeCl3, or 0.05M HEPES, then implanted subdermally in weanling male rats (40-60 gm) for 21, 60, 90, and 120 days. At explant, Fe3+ and Ca2+ levels were measured by atomic absorption spectroscopy. Fe3+ effectively inhibited calcification in both experimental groups compared to control through the longest implant (Ca2+ levels, 120 day implant: 0.1M FeCl3 = 46.85 +/- 17.45 micrograms/mg; 0.01M FeCl3 = 17.31 +/- 7.38 micrograms/mg; control = 258.04 +/- 15.71). Measurement of explanted GPBP Fe3+ levels showed that tissue Fe3+ levels of at least 7.28 +/- 0.70 micrograms/mg were required to effectively inhibit calcification after a 120 day implant. There was no evidence of Fe3+ impairment of rat growth. In conclusion, Fe3+ pretreatment of GPBP significantly inhibited calcification after long-term (120 day) rat subdermal implant. PMID- 1751097 TI - In vitro evaluation of a stentless porcine aortic bioprosthesis. A preliminary study. AB - Currently available aortic bioprosthetic heart valves are all relatively suboptimal due to the constraints placed on leaflets by stenting. The constraints on the stenting mechanism may directly or indirectly cause turbulence in the orifice neighborhood, be nidi of tissue calcification, and impart transleaflet stress differentials. To address all these deficiencies, we undertook the development of a stentless porcine aortic bioprosthesis (SPAB). This study evaluates the hemodynamic performance and durability of this design in special chambers with near physiologic compliance. The results are compared to those shown by a stented porcine aortic bioprosthesis. The pressure measurements under steady flow conditions showed that the hemodynamic performance (including pressure gradient and effective orifice area) of SPAB is superior to that of its stented counterpart, especially in the smaller sizes. In addition, it is expected that this stentless design should minimize the mechanical stress to which the leaflets are subjected throughout the cardiac cycle, thus enhancing the durability of the bioprosthesis. In our accelerated durability study for up to 2 equivalent years, no valve failure has been observed. More in vitro studies under pulsatile flow conditions, including color Doppler flow visualization, are currently being conducted. PMID- 1751098 TI - Improved biocompatibility of bovine pericardium using a new method of cross linking. AB - The authors used glycerol (Gly) as a cross linking agent to treat bovine pericardium (BP) and compared it mechanically (tensile test) and biologically (subcutaneous implantation in rats) with glutaraldehyde (Glu) fixed lonescu Shiley BP (ISBP). Maximum tensile stress (Stmax) was the same in both groups (n = 12 each), while maximum strain (Snmax) was larger in Gly BP. Calcium content (Ca) was lower and water content of tissue (WC) was higher in implants of Gly BP versus ISBP (n = 9 each). Gly BP appeared more hydrated than ISBP in specimens studied by scanning electron microscopy (SEM). In addition, SEM of three Gly BP mitral valves in sheep showed good growth of endothelial (En) cells. These biomechanical advantages of Gly BP over ISBP suggest that Gly may be a useful substitute for Glu in cross linking bovine pericardial valves. PMID- 1751099 TI - A newly designed anticancer tumor immunity drug delivery system. AB - The authors used a fibrin clot (FC) as a carrier of an anti-cancer drug (AD) to achieve sustained release of the drug. Adriamycin (ADM) and cis-platinum (CDDP) were individually encapsulated into an FC, and the profile of release of each AD from the FC-AD was examined in vitro. The FC-AD was placed intra-abdominally in ascites hepatoma AH130-bearing rats, and ADM or CDDP solution was intraperitoneally injected (IP) into other cancer bearing rats. The survival time was recorded, and related oncolytic mechanisms were investigated. The release of AD from the FC continued for over 15 days. Sixty-eight percent of the rats treated with FC-AD survived for more than 200 days and evidence of malignancy disappeared. Almost all of the IP rats and non-treated rats died within 20 days; these animals had massive ascites and extensive metastases. Immunologic studies confirmed that various tumor immunoresponses were induced in the rats treated with FC-AD. The FC-AD system warrants further study for possible antineoplastic activities in vivo. PMID- 1751100 TI - Application of finite element analysis for assessing biocompatibility of intra arterial catheters and probes. AB - A commercial finite element modeling program (FIDAP) was adapted to compute the fluid dynamics of laminar blood flow around an intra-arterial catheter and/or sensor probe. The model provided an accurate transient solution to the Navier Stokes equations under pulsatile blood flow conditions. To simulate the compliance in the catheter tubing set, a second order convolution integral was incorporated into the boundary conditions. The saline drip rate and catheter compliance could be specified, and the bulk blood flow, blood pressure, and heart rate were varied to simulate specific patient conditions. Analysis of the transient solution was used to assess probable sites for thrombus activation and deposition. The transient velocity and pressure fields identified regions of separated flow and recirculation. The computed shear rates and stresses were used to predict hemolysis, platelet activation, and thrombus formation. Analysis of particle paths provided an estimate of residence times and thrombus deposition sites. PMID- 1751101 TI - Effects of dialysis factors and route of administration on response of hemodialysis patients to recombinant human erythropoietin. AB - Data on the use of recombinant human erythropoietin (rHuEPO) were obtained from 25 hemodialysis centers to determine whether route of administration (intravenous [i.v.] vs. subcutaneous [s.c.]) or various dialysis factors influenced the response to rHuEPO; 844 of 958 patients had sufficient data for evaluation. Hematocrit (HCT) increased from 23.8 to 29.1% after a mean rHuEPO treatment period of 202 days; 48.4% of all patients did not reach a HCT greater than or equal to 29%. The s.c. route increased HCT more than the i.v. route. Multivariate analysis of the response (i.e., increase in HCT from baseline) showed a positive correlation with more rapid dialysis but a negative correlation with reuse, baseline HCT, transfusion dependence, and frequency of administration. The effects of dialysis and reuse were not present when the response was normalized by weekly dose. It was concluded that one half of all patients treated did not attain the recommended target HCT, perhaps due to economic constraints or resetting of goals. The s.c. route may be preferable to optimize response. PMID- 1751102 TI - Is hematologic response to iron and erythropoietin in hemodialysis patients affected by other factors? AB - Multiple factors have been implicated in the hematologic response to erythropoietin (EPO). The authors studied 54 hemodialysis patients; 44 received 1.5 g of iron intravenously, 16 received oral iron for 12 weeks, and 24 were treated with EPO. Some patients received these treatments in sequence. The factors evaluated were serum albumin, protein catabolic rate, serologic evidence of hepatitis B or C, parathormone (PTH), and aluminum levels. Red cell production was expressed as milliliters of red blood cell increase per day per kilogram of body weight. For patients receiving EPO, hematologic response was normalized to 50 U/kg/dialysis. Of the patients on oral iron, 31% had a good response (hematocrit greater than or equal to 30%). Of the patients who received iron intravenously, 50% had a good response (hematocrit greater than or equal to 30%). All patients treated with EPO responded well, except for one patient who did not respond to doses of EPO up to 200 U/kg/dialysis. The response to intravenous iron dextran was more rapid than the response to oral iron or EPO. Nutritional factors (serum albumin and protein catabolic rate), serologic evidence of hepatitis, elevated PTH levels, or elevated aluminum levels did not significantly affect the response to iron supplementation or EPO treatment. PMID- 1751103 TI - Determinants of dialyzer reuseability. AB - The authors observed a wide variability in the number of uses per dialyzer in their hemodialysis patients. In 54 patients who reused their dialyzers, heparin dose (U/kg/min) related directly and white blood cell count related inversely to reuseability. Average reuse was 5.1 +/- 2.9 (SD) in diabetics (n = 13) and 7.8 +/ 3.8 (SD) in non-diabetics (n = 41; p = 0.007). Of the diabetics, 77% achieved six or less reuses, and 59% of non-diabetics achieved six or more reuses (chi square = 4.96; p less than 0.05). In non-diabetics, heparin dose was the most significant determinant of reuse, and in diabetics the major determinant was white blood cell count. Hematocrit levels, platelet count, erythropoietin use, or type of membrane (polysulfone/cellulose acetate) did not correlate with reuseability. It was concluded that reuseability of dialyzers is less in diabetic patients, patients on lower heparin doses (U/kg/min), and patients with higher white blood cell counts. Determinants of dialyzer reuseability warrant further study. PMID- 1751104 TI - Effect of erythropoietin on neutrophil chemiluminescence in hemodialyzed patients. AB - Erythropoietin (EPO) has been used widely for correcting anemia in hemodialyzed (HD) patients. Enhancement of phagocytic function during EPO treatment of HD patients has been studied, but no data have been available on the effect of EPO on neutrophil chemiluminescence (CL) after challenge with phorbol myristate acetate (PMA). CL was measured in prehemodialysis whole blood samples from 15 stabilized patients and 15 normal healthy control subjects (C) after challenge with PMA. Before EPO treatment, CL was noted to be significantly higher in HD patients than in C, which changed significantly after 5 weeks of treatment (Rx) and continued for 13 weeks of Rx. There was a significant increase in hematocrit in these HD patients after 5 weeks that persisted until the 13th week. It was concluded that there is a significant decrease in whole blood CL in response to challenge with PMA during correction of anemia in HD patients treated with EPO. This study demonstrated that EPO could decrease enhanced PMA-activated reactive oxygen metabolite production and suggested that this decrease may protect against tissue damage, including red blood cell hemolysis in the uremic milieu. PMID- 1751105 TI - Performance evaluation of hydroxylated and acylated silicone rubber coatings. AB - Hydroxylated and C16 acylated silicone rubber films were prepared with enhanced albumin binding. Lee-White clotting times were significantly increased for both treatments. Hydroxylation significantly reduced C5a production. Hydroxylated silicone rubber femoral vein catheters in canines reduced 111In-labeled platelet activity, compared with bilateral silicone rubber catheter controls. The results suggest hydroxylated silicone rubber films have enhanced biocompatibility. PMID- 1751106 TI - Nafamostat mesilate administration during cardiopulmonary bypass decreases postoperative bleeding after cardiac surgery. AB - The hemostatic effect of nafamostat mesilate (FUT-175) was evaluated in patients undergoing cardiopulmonary bypass (CPB) surgery. Thirty patients undergoing aortocoronary bypass grafting were divided into two groups. In the control group, anticoagulation was achieved with an initial dose of heparin (3 mg/kg). In the FUT-175-treated group, in addition to the ordinary treatment with heparin, FUT 175 was infused continuously into the circuit throughout the procedure at a rate of 100 mg/hr. Thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), and fibrin degradation products (FDP-D) dimer increased in both groups as CPB proceeded. In the FUT-175-treated group, these parameters remained lower and decreased more rapidly after the end of CPB. Alpha 2 plasmin inhibitor/plasmin complex (PIC) increased progressively during CPB in the control group; no such significant increases were seen in the FUT-175-treated group. Postoperative blood loss was significantly lower in the FUT-175-treated group than in the control group. It was concluded that FUT-175 reduces postoperative blood loss by inhibiting both coagulation and fibrinolysis during CPB. PMID- 1751107 TI - Development of thermosensitive peptidyl cell substrate synthesis and artificial fibrin glue. AB - A totally synthetic fibrin glue was developed. The molecular structure is a co polymer of N-isopropyl acrylamide (NIAM) and vinyl monomer units with a cell adhesion peptidyl moiety (Arg-Gyl-Asp). The buffer solution is a viscous liquid at room temperature, but spontaneous precipitation occurs due to thermoresponsive phase transition derived from poly-NIAM. The peptidyl moieties bind to platelet receptors. When applied to tissues, spontaneous precipitation and subsequent platelet aggregation occurred, indicating that the synthetic bioactive polymer effectively functions like fibrin glue. PMID- 1751108 TI - Fibronectin surface density affects endothelial cell function and growth on hydrophilic polymer. AB - Adhesive biomolecules have been used to promote endothelial cell adherence to polymer surfaces. The authors varied the surface density of one such biomolecule (fibronectin) applied to a hydrophilic polymer in an in vitro model system and then measured the amount of prostaglandin E2 (PGE2) produced by endothelial cells grown on these modified polymers. Endothelial cells grown on polymers with fibronectin applied at a surface density of 10 and 35% produced significantly more PGE2 (25.7 +/- 2.1 and 26.8 +/- 0.9 pg, respectively) than cells grown on polymer with no fibronectin (7.3 +/- 1.0 pg) and with complete saturation of the polymer surface with fibronectin (13.1 +/- 5.3 pg), with a p less than 0.005 for the comparison. The surface density of biomolecules on an artificial substrate is an important determinant of endothelial cell function. PMID- 1751109 TI - Development of a new scrim cardiac wall substitute. AB - A cardiac wall substitute made of non-woven ultrafine fibers was developed. It consists of a basal knitted scrim with strongly entangled ultrafine polyester fibers, lined with a fine velour of entangled ultrafine fibers that provide high ravel and tear resistance, a perfect matrix for preclotting, and an anchor for cell adhesion. Six of the new patches and all control patches (a polytetrafluorethylene patch, woven Dacron patch, and glutaraldehyde-treated equine pericardium) were implanted in the right ventricular outflow tracts in 24 dogs. Animal experiments showed that the new patch was easy to handle and suture without fraying or tearing through the edge. PMID- 1751110 TI - Experimental evaluation of a new type of heparin-bonded polyurethane. AB - A new type of heparin bonding method using polyurethane (H-PU) in an ionically equivalent manner was examined experimentally. In vitro testing of polyvinylchloride tubes with this coating showed that the behavior of the heparin was attributed to the activation of retained heparin on the surface. After 4 hrs of heparinless arterio-arterial bypass in a canine model with a central shear rate of 25 sec-1 (inner diameter, 0.8 x 80 cm), macroscopic and scanning electron microscopic examinations showed that the H-PU coated tube had better antithrombogenicity than that of a conventional PU coated tube (Pellethane). These results suggest that this heparin bonding method with PU appears to have good antithrombogenicity with possible long durability. PMID- 1751111 TI - Electric power induction through an isolated intestinal pouch. AB - A new transintegumental power transformer uses the walls of an isolated intestinal pouch to separate primary and secondary coils. It may surpass transcutaneous devices in heat dissipation potential and in comfort. It was acutely tested in 13 dogs. Corrections in geometry and insulation were suggested by the nine initial trials. In the remaining four animals, up to 14.1 W were delivered, incrementing over 90 to 395 min. Three pouch and two remote thermistors recorded temperature (T) at 10 min intervals. Thirty sets of data were taken at 4 W or less (Group A), 31 at 4-8 W (Group B), and 16 at more than 8 W (Group C). T elevations above reference drift were 0.096 + 0.062 degrees C, 0.468 + 0.234 degrees C, and 0.876 + 0.156 degrees C for groups A, B, and C, respectively. These were significant by t-tests (p less than 0.001 for Group A vs. B; p less than 0.05 for Group B vs. C). The concept appears to be feasible, and longer term implantation trials seem justified. PMID- 1751112 TI - A servomatic pneumatic driver system for left ventricular assist devices. AB - A new ventricular assist device (VAD) pneumatic driver with a servomatic left atrial pressure (LAP) control mechanism was developed for easy and safe control of left ventricular assist devices. The negative driving pressure (NP) can be automatically varied to control the assisted circulatory flow (AF), comparing the patient's LAP with prescheduled LAP (s-LAP). Animal experiments revealed this servomatic control system to be useful. PMID- 1751113 TI - Electrohydraulic ventricular assist device development. AB - A 64 ml (effective stroke volume) in vitro electrohydraulic ventricular assist device (VAD) prototype has been built. The energy converter is an axial flow pump driven by a brushless direct current (DC) motor. Systole begins as silicone oil is pumped from the volume displacement chamber (VDC) into the ventricle, displacing the flexing diaphragm separating the oil and the blood. In diastole, the motor reverses, providing active filling by pumping oil from the ventricle into the VDC. The surface mount electronic internal controller provides motor commutator, energy management, telemetry, and physiologic control functions. Energy is supplied externally by either a 12 V DC power supply or a 12 V DC rechargeable battery and is transmitted through the skin by a transcutaneous energy transformer (TET). Energy can also be supplied by a 12 V DC rechargeable internal battery. Bidirectional infrared telemetry is used to transmit information between the internal and external controllers. PMID- 1751114 TI - Control of pulsatile rotary pumps without pressure sensors. AB - When ventricular assistance is achieved with a volumetric pump driven by an electric actuator, overpumping can cause venous collapse. To prevent this problem, pump speed must be monitored and controlled. The authors developed a regulatory system based on the current intensity signal from the electric motor. This signal is processed and compared with predicted values calculated according to a mathematical model at the beginning of each ejection phase. If a difference is detected, pump speed is adequately adjusted. The great advantage of this system is elimination of the need for an implantable pressure sensor. It requires a simple and ubiquitous electronic component, i.e., a resistor, that can be easily integrated into the motor control circuit and does not require calibration. PMID- 1751115 TI - A sophisticated electromechanical ventricular simulator for ventricular assist system testing. AB - With the advent of chronically implanted left ventricular assist systems, new adaptive control algorithms are being developed to allow automatic device control under a variety of hemodynamic conditions. An electromechanical pump is described that accurately mimics ventricular function. A pusher-plate sac pump with tri leaflet valves is coupled to a high-speed linear motor. Pump chamber volume and pressure are constrained to follow the time-varying elastance model of ventricular function by use of a microprocessor feedback loop. PMID- 1751116 TI - A model of right ventricular failure after global myocardial ischemia and mechanical left ventricular support. AB - Postcardiotomy right ventricular (RV) failure after institution of mechanical left ventricular (LV) support is poorly understood. Using a canine model supported by cardiopulmonary bypass (CPB), the animals underwent 30 min of aortic clamping or no ischemia and were weaned to an LV assist device (LVAD). Echocardiographic measurements of LV and RV cavity size off support allowed calculation of percentage change in cavity area (fractional shortening). There were no differences at baseline. After 2 hrs on LVAD, there were significant differences between ischemic and control groups in both LV (38 +/- 12 vs. 61 +/- 6) and RV (15 +/- 3 vs. 55 +/- 12). The ischemic RV also had significantly decreased function compared with the LV (38 +/- 12 vs. 15 +/- 3). The control group demonstrated no differences in ventricular function. The authors concluded that global ischemia diminishes LV and RV function, and this effect is accentuated in the RV after LVAD support. In controls, RV function is not affected by LVAD support, but after ischemia, LVAD support alone often will be inadequate. PMID- 1751117 TI - Reconstructed image of the human heart based on magnetic resonance images for total artificial heart implantation. AB - Parameters used to develop a three-dimensional reconstructed image of the remaining heart after total artificial heart implantation (i.e., for the mitral and tricuspid annuli, ascending aorta (AO), and pulmonary artery [PA]) were calculated based on reconstructed images from data obtained from four magnetic resonance (MR) image views: 1) transverse, 2) coronal, 3) left ventricular long axis (LAX), and 4) four chamber view (FCV). The values obtained were compared with those obtained from silicone models of the same hearts. It was found that, of the four MR image views, LAX and FCV provided the greatest numbers of points reflecting annular contour that were useful in reconstruction of the atrioventricular (AV) annuli, and the highest percentages of segmented outline connecting points less than 1 cm apart for the total outline. The AV annuli were sliced in the least slice time using FCV imaging. The authors applied FCV MR imaging to a beating heart to reconstruct the AV annuli and obtained accurate results. To quantify more accurately the data for the axis directions of AO and PA, research to establish a new orientation on the thorax is in progress. PMID- 1751118 TI - Anatomic study for in vivo evaluation of a total artificial heart in calves. AB - A poor fit will negate any physiologic evaluation of an implantable total artificial heart (TAH). Fifteen Holstein calves (weight, 65-111 kg) were used to measure intrathoracic dimensions for TAH design, to find correlations between intrathoracic and external parameters for preoperative animal selection, and to suggest minor modifications for fitting a TAH in calf chests. The following dimensions were found to be critical to avoid compromising venous return: 1) mitral annulus center (MVC)-sternum, 10.4 +/- 1.0 cm; 2) tricuspid annulus center (TVC)-sternum, 9.8 +/- 1.6 cm; 3) MVC-TVC, 5.5 +/- 0.4 cm; 4) MVC-diaphragm, 3.4 +/- 0.8 cm; 5) MVC-left chest wall, 4.5 +/- 0.9 cm; and 6) TVC-right chest wall, 4.5 +/- 1.0 cm. These dimensions had no statistically significant correlation with body weight, but three of them did with the following external parameters: 1) bronchial carina-sternum on chest radiograph, p less than 0.05; 2) dorsoventral dimension at xiphoid, p less than 0.05; and 3) circumference at the caudal end of the scapula, p less than 0.05. Based on these results, the port orientation of the left housing of this electrohydraulic TAH designed for humans was modified for in vivo evaluation in calves. No other pump features required change. These data should prove useful to others involved in TAH development. PMID- 1751119 TI - Blood compatibility of the jellyfish valve without anticoagulant. AB - The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use. PMID- 1751120 TI - Liquid nitrogen snap frozen saphenous vein for vascular access in dialysis. AB - In the authors' centers, fresh saphenous veins (FSV) procured from routine saphenectomies have been preferred to synthetic prostheses in cases of difficult vascular accesses (VA) for dialysis. The need for veins of different lengths and diameters prompted them to preserve SV by instantaneous freezing in liquid nitrogen since November 1987. Until now, 59 patients have received 35 FSV and 32 cryopreserved SV (CSV). Actuarial patency rates after 1 year are 82% and 72%, respectively. The 6-keto prostaglandin F1 alpha measured on punches of both veins showed residual production of prostacyclin even in CSV, but this was unresponsive to stimulation by arachidonic acid and bradykinin, or to inhibition by aspirin. In the authors' opinion, despite marked endothelial damage, satisfactory clinical results can be obtained by this very simple and cheap method of storing biologic prostheses for dialysis VA. PMID- 1751121 TI - Antidiuretic hormone regulation in hemodialysis. AB - The relative influence of stimulation and suppression of osmoreceptors and low and high pressure baroreceptors was studied in 12 patients on hemodialysis. The stimuli were separated by ultrafiltration and dialysis. When high and low baroreceptors were deloaded by volume contraction during ultrafiltration, but there was no change in osmolality, the antidiuretic hormone (ADH) level rose steeply. When osmoreceptors were suppressed, but there was no influence on baroreceptors during dialysis, ADH level declined by the same amount it had increased during ultrafiltration. When osmoreceptors were stimulated by an increase in osmolality in the phase between dialyses, but baroreceptors were loaded by an increase in volume, ADH levels did not change. Others showed that when baroreceptors are stimulated and osmoreceptors suppressed during simultaneous ultrafiltration and dialysis, there is also no change in ADH levels. These results indicate that the hierarchy of receptors regulating ADH is osmoreceptors followed by high and low baroreceptors. Simultaneous stimulation or suppression of both baroreceptors appears equal to the influence by osmoreceptors. PMID- 1751122 TI - Protamine-coated Cuprophan. A potential nonthrombogenic hemodialysis membrane with improved blood compatibility. AB - A protamine-coated Cuprophan hemodialysis membrane possessing improved blood compatibility was developed. Protamine was covalently immobilized onto the inner walls of the Cuprophan hollow fibers, using the cyanogen bromide (CNBr) activation method. Studies conducted with aqueous solutions indicated that the immobilization process did not introduce deterioration of the membrane mechanical and mass transfer properties; the permeability of several compounds through the protamine-coated membrane was unchanged. The modified membrane was rendered nonthrombogenic by the adsorption of heparin to the protamine-bound surfaces. Heparin adsorbed on the immobilized protamine retained about 20% of its initial anticoagulant activity. Preliminary studies using the hemolytic complement assay indicated that complement activation by the protamine-coated membrane was statistically far less than that by the untreated membrane. PMID- 1751123 TI - Continuous measurement of pressure in internal arteriovenous fistulae and prevention of symptomatic hypotension during hemodialysis. AB - To continuously monitor the blood pressure (BP) in an internal arteriovenous fistula, the blood tubing wall was punctured with a long, fine needle (25 gauge), and the needle tip was advanced into the fistula vein through the lumen of the outflow blood access puncture needle. It was found that the intrafistula BP thus measured varied in parallel with the systemic arterial BP during hemodialysis (HD). When the intrafistula BP fell to 60% of the level at the start of HD, 50 ml of saline was administered. As a result, hypotension was prevented completely in 60 HD in five patients who often showed symptomatic hypotension during HD. PMID- 1751124 TI - The use of the Gianturco intravascular stent in stenotic hemodialysis fistulas. AB - This study was initiated to investigate the use of the Gianturco intravascular stent in prolonging dialysis access graft patency after angioplasty. Stents were placed in 25 patients with follow-up to date of 0.5-8 months. The stent used was 1.5 x 3 cm and consisted of two units connected by a single strut. In Phase 1, the strut was rigid, and the stent had no barbs. The rigidity of the stent and stent migration caused problems. In Phase 2, an articulated strut design was used, and in Phase 3, barbs were added. These modifications solved the previously noted problems. No anticoagulation was used, and clotting was not a significant problem. The duration of patency for the total group was not significantly better than for control groups. However, there were no losses with the modified stent design used in Phases 2 and 3 with follow-up to date of 0.5-5.5 months. Further study of this treatment modality appears warranted. PMID- 1751125 TI - Glomerulopressin in end-stage renal disease. Effect of hemodialysis. AB - Plasma and hemofiltrate activities and hemodialysis (HD) clearance of glomerulopressin (GP) were measured in eight end-stage renal disease (ESRD) patients. Four normal volunteers served as controls. Plasma GP was elevated significantly in the ESRD group and fell with HD. Significant amounts of GP were found in the hemofiltrate. Single passage through the dialyzer resulted in a 24.7% fall in plasma GP activity. Dialyzer clearance of GP averaged 144 ml/min (75.4% of urea clearance). In conclusion, plasma GP was elevated in ESRD and readily removed by HD. PMID- 1751126 TI - A completely implantable total artificial heart system. AB - The authors developed, built, and tested in vivo a completely implanted total artificial heart (TAH) system. The system used a reduced size version of a roller screw energy converter and mating sac blood pumps. The motor drive, pumps, and a compliance chamber were implanted intrathoracically. A canister containing controlling electronics and an emergency battery was implanted in the abdomen. The secondary coil of an inductive energy transmission and telemetry system was placed over the ribs. The system was implanted in three calves, that survived 0.5 13 days with the system. The system maintained safe left atrial pressures and adequate cardiac outputs during each animal's entire course. PMID- 1751127 TI - A unique, efficient, implantable, electromechanical, total artificial heart. AB - A completely implantable, one piece electromechanical total artificial heart (TAH) intended for permanent human use was developed. It consisted of left and right conically shaped pusher-plate blood pumps sandwiching a thin centerpiece with a compact, efficient electromechanical actuator. The actuator consisted of a direct current brushless motor; a planetary roller screw fit the space between the two conically shaped pusher-plates. The rotational motion of the motor was converted to the rectilinear motion of the rollerscrew to displace the left and right pusher-plates in the left master alternate mode. The diameter of the assembled TAH was 97 mm, with a central thickness of 82 mm. The overall weight was 620 g, with a displaced volume of 510 ml. The pump provided flows of 3-8 L/min with a preload of 1-15 mmHg against an afterload of 100 mmHg. The net efficiency ranged from 15% to 18%. This model showed good fit in the pericardial space of heart transplant recipients (body weight, 77 kg). PMID- 1751128 TI - The newly designed univalved artificial heart. AB - A univalved artificial heart (AH) powered electromagnetically in the frequency range of 1-30 Hz was developed to obtain a totally implantable AH. This small sized AH consisted of a vibrating tube, coils, magnets, and a jellyfish valve as an outlet AH valve. The fluid mechanical, hemodynamic, and hematologic properties were evaluated in a mock circulation and 10 animal experiments using adult goats. This vibrating electromagnetic AH could generate more than 10 L/min as an output volume, with 10 Hz vibration using 20 volts supplied voltage. It could also provide two kinds of flow and pressure patterns, in constant-peak and periodic peak patterns. The values of free hemoglobin remained within acceptable limits. The authors concluded that this new type of pump was useful as a totally implantable AH, ventricular assist, or organ assist system. PMID- 1751129 TI - A new pulsatile total artificial heart using a single centrifugal pump. AB - A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH. PMID- 1751130 TI - Chronic evaluation of a compact nonseal magnet pump as a nonpulsatile pump for long-term use. AB - Use of a nonpulsatile pump is one of the most interesting approaches in the development of artificial hearts. A centrifugal pump without a seal around the rotating part was evaluated in five goats. The size of the pump is 8.4 cm x phi 7.0 cm, including an electric motor. A polypropylene impeller with four fins on the top of a column in which a magnetic ring is embedded spins by coupling with a rotating magnet outside the housing. In the goats, the pump was placed paracorporeally to provide total left heart bypass at a flow rate of 4.6-7.6 L/min, and activated clotting time was controlled at 200-300 sec by continuous heparin infusion. Although the first three goats died within 3 days due to bleeding, embolism, and a jammed impeller, respectively, a pump could be driven for 14 days in the fourth goat, and another pump with a rotational control feedback system ran for 32 days in the fifth goat. Plasma free hemoglobin levels were 13.8 +/- 4.3 mg/dl and 9.5 +/- 2.5 mg/dl, and platelet counts were 53.8 +/- 24.7 x 10(4)/mm3 and 62.0 +/- 22.0 x 10(4)/mm3 after 12 hours and 7 days pumping, respectively. No thrombus was observed in the blood chamber in the last two cases. In conclusion, this pump has possibilities as a nonpulsatile pump for long term use. PMID- 1751131 TI - Spherical rotary piston machine as an artificial heart. AB - A positive displacement pump with six rotary pistons was proposed as an artificial heart. The pump's design was characterized by high symmetry and compactness. Thus, a spherical volume of 4 1/4 inch diameter sufficed for a pump delivering 10 L/min at 120 pulses/min with the pistons turning at 30 rpm. The pistons and four connecting gears were the only moving parts. The pump functions in two separate halves as left and right ventricles, with two of the six pistons each having inlet and outlet passages, and one of them replacing mitral and pulmonary valves with the other, tricuspid and aortic valves. The function of the intraventricular septum was provided by the other four pistons whose interiors also accommodated driving motors each capable of 0.4 Nm torque for a combined power of 5 watts. There were no stagnant regions in the pumping volume, and at all internal surfaces in contact with blood, there was periodic shear stress not exceeding approximately 300 Pa. PMID- 1751132 TI - Atrial compliance changes in animal total artificial heart recipients. AB - Right atrial compliance of chronically implanted total artificial heart animals was calculated from the pressure-volume relationships acquired at autopsy and compared with those of a control animal. The chronically implanted animals showed right atrial dilatation and low compliance. Even though atrial dilatation and decreased compliance have an opposite direct effect on atrial pressures, these changes may, in turn, disturb stretch-dependent volume regulatory processes, resulting in high atrial pressure. PMID- 1751133 TI - A biolized, compact, low noise, high performance implantable electromechanical ventricular assist system. AB - An implantable electromechanical ventricular assist system (VAS) intended for permanent human use was developed. It consisted of a conically shaped pumping chamber, a polyolefin (Hexsyn) rubber diaphragm attached to a pusher-plate, and a compact actuator with a direct current brushless motor and a planetary rollerscrew. The outer diameter was 97 mm, and the total thickness was 70 mm. This design was chosen to give a stroke volume of 63 ml. The device weighs 620 g, with a total volume of 360 ml. The pump can provide 8 L/min flow against 120 mmHg afterload with a preload of 10 mmHg. The inner surface of the device, including the pumping chamber and diaphragm, was made biocompatible with a dry gelatin coating. To date, two subacute (2 and 6 day) calf studies have been conducted. The pump showed reasonable anatomic fit inside the left thorax, and the entire system functioned satisfactorily in both the fill-empty mode using the Hall effect sensor signals and the conventional fixed rate mode. There were no thromboembolic complications despite no anticoagulation therapy. The system now is being endurance tested greater than 10 weeks (9 million cycles). This VAS is compact, low noise, easy to control, and has excellent biocompatibility. PMID- 1751134 TI - Determination of critical pericardial dimensions in patients with dilated cardiomyopathy. AB - The development of orthotopically positioned cardiac replacement devices requires a knowledge of the space available to guide the design of the blood pumping system. Pericardial dimensions from in vivo and cadaver studies of normal subjects have been reported, but little information is available on in vivo pericardial dimensions in patients with dilated cardiomyopathies. The critical pericardial dimensions were determined in 13 men who were cardiac transplant recipients (age, 42 +/- 13 years; body mass, 72 +/- 11 kg; three with ischemic and 10 with idiopathic cardiomyopathy) by comparison of corresponding pericardial axes on chest radiographs to measurements obtained during orthotopic cardiac transplant in the context of a total artificial heart fit trial. The main pericardial dimensions measured intraoperatively were found to be the T10 midline anteroposterior (AP) axis (12.3 +/- 1.4 cm), the aortic root to diaphragm length (9.7 +/- 1.5 cm), the T10 total cardiac lateral axis (18.1 +/- 2.3 cm), and the tricuspid annulus to left ventricular apex (12.1 +/- 1.7 cm). All patients had cardiomegaly as indicated by a greater than normal cardiothoracic ratio. These data described the limited dimensions of the pericardial space available for orthotopic cardiac replacement devices. Chest film dimensions can be corrected using 0.92 and 0.88 as reduction factors for the (AP) and lateral axis dimensions, respectively. In this patient sample, there was little or no correlation between pericardial dimension and patient body mass or diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751135 TI - Anatomic fit study for development of a one piece total artificial heart. AB - A fit study was conducted to define anatomic constraints to total artificial heart (TAH) insertion in 26 human orthotopic cardiac transplant recipients, and the parameters necessary for designing a totally implantable TAH were obtained from the excised heart. A multiadjustable fitting device was made (height, 118 mm; width, 81 mm; diameter, 97 mm), and with this model, 15 fitting and measuring studies were conducted to validate the design and demonstrate anatomic compatibility. Satisfactory fit of the contour model was observed in all cases. The model was placed through a sternotomy wound in the pericardial space. In addition to this mock-up fit study, the anatomic dimensions of the connection points to the TAH and the excised hearts also were measured. With the prototype model based on these data, a fit verification study was done in 11 recipients. Satisfactory fit in the pericardial space without compression of adjacent structures was observed in seven of 11 patients. This study suggests that the newly designed model of an anatomically and surgically practical configuration could be implanted in most patients in this population as a completely implantable cardiac prosthesis. PMID- 1751136 TI - Microbially infected thrombus in animals with total artificial hearts. AB - In a retrospective study of 330 animals with total artificial hearts (TAH), 103 (31%) had microbially infected thrombi (MIT). The incidence of MIT approximated 75% in the animals surviving more than 100 days. The most common pathogen isolated from animals with MIT was Pseudomonas. Most thrombi appeared to have originated from valve junctions and connectors. Methods to prevent MIT should be aimed at eliminating thrombus formation by improved design and materials and controlling the route of bacterial colonization. These findings suggest that bacterial interaction with the thrombus, device-related bacterial colonization, host immunomodulation, and gut barrier function after TAH implantation need further study. PMID- 1751137 TI - Device related infections in patients supported with mechanical circulatory support devices for greater than 30 days. AB - Mechanical circulatory support with systems that require transcutaneous cannulas or drive lines are associated with a high incidence of device related infections. The development of infection often is related to the duration of support. Data were reviewed on 10 patients (nine men and one woman) supported with assist devices (Thoratec-five, Nova-cor-three, Sarns-one, Jarvik-one) for longer than 30 days (range, 31-440; mean, 137 days). Seven patients had device related infections. Five also had positive blood cultures with the same organisms responsible for the device related infection. Two had mediastinitis from an ascending infection (one cannula and one drive line). Eight patients were transplanted, with seven survivors. One patient was weaned and survived, and one died during support. These data show that device related infections are common and severe, but they do not preclude successful transplantation, weaning, or survival. PMID- 1751138 TI - Platelet deposition on polyethylene. Dependence of second layer platelet attachment on von Willebrand's disease plasma. AB - The role of von Willebrand's factor (VWF) was examined in platelet deposition on polyethylene by exposing 3/16 inch diameter discs of polyethylene to 111In labeled platelets re-suspended in citrated blood from normal and severe von Willebrand's disease donors. Discs were oscillated for 30 and 60 min, washed, fixed, counted for 111In, and examined by scanning electron microscopy (SEM). Total platelet deposition in the 0% VWF group was significantly greater than control discs at 30 min (7.0 x 10(6) +/- 0.5 compared with 3.29 x 10(6) +/- 0.6 platelets/cm2). The SEM examination revealed patches of spread platelets, with platelets adhering to platelets in controls. A dense, uniform monolayer of platelets was found on the 0% VWF discs. At 60 min, control discs had significant increases in the platelet deposition with SEM examination revealing uniform coverage of the disc with additional platelets. PMID- 1751139 TI - The three-dimensional relationships between mitral and tricuspid valvular annuli for total artificial heart implantation. AB - The three-dimensional relationship between the mitral valvular annulus (MVA) and tricuspid valvular annulus (TVA) was studied in 32 cadaver hearts. It was found that when the distance from the center of the MVA and TVA (D-G) were standardized and when MVA and TVA were overlapped by matching their centers, MVA was located in the fan shaped region in the lateral view of the TVA and pointed toward the orifice of the coronary sinus. D-G was correlated with the volume of the space occupied by both ventricles. When the value of D-G was standardized, TVA remains free to change its shape and orientation toward either the cranial or caudal direction. PMID- 1751140 TI - Determination of atrial shunt size needed to balance an electrohydraulic total artificial heart. AB - An interatrial shunt (IAS) was developed and tested to balance a volumetrically coupled electrohydraulic total artificial heart (EHTAH). The IAS diameter was determined theoretically with the equation: [formula: see text] where D = orifice diameter, delta P = pressure drop across the orifice, rho = fluid density, Q = volume flow through the orifice, and C = empiric constant. The calculated orifice diameter was 2.9-5.3 mm to keep a 3-5 mmHg pressure difference between left and right atria, with 0.42-1.05 L/min of expected flow through the IAS. Three different sizes (3.4, 5.4, and 5.5 mm) of IAS were implanted and tested in four calves. The in vivo left-right pressure difference ranged from 3 to 8 mmHg, with 0.57-1.38 L/min of theoretically calculated flow through the IAS. At autopsy, none of the IAS showed macroscopic thrombus formation. PMID- 1751141 TI - In vitro testing of venous valves. AB - The need to test prosthetic venous valves led to the design of a hydraulic mock circuit that reliably mimics natural venous flow. Components of this system simulate calf muscle pump and thoracoabdominal suction pump action. Flow and pressures are serially measured along the circuit. Valve function can be observed and videotaped. Evaluation of biologic venous valves provides visual and quantitative assessment of venous valve function with respect to tissue processing, valve design, and implantation technique. Further improvement in this system in terms of more compliance and less rigidity of components is being pursued. PMID- 1751142 TI - Laser welding and irradiation in alcohol preserved homografts. AB - This experiment examined the effect of laser welding and irradiation on the patency rate of microvascular anastomoses done with alcohol preserved homografts. The carotid arteries from Sprague-Dawley rats were freshly harvested and preserved in 70% ethyl alcohol for at least 3 weeks. The homografts were interposed into the carotid arteries with one of the following techniques: Group I, grafts were anastomosed with three stay sutures and laser welding (carbon dioxide laser, 90 mW); Group II, anastomoses were completed with eight to nine interrupted sutures (10-0 nylon); or Group III, the same technique used in Group II, but followed by laser irradiation (90 mW for 1 min) of the grafts. These results showed that patency at 2 weeks was 73% in Group I, 71% in Group II, and 82% in Group III, respectively. The patency at 12 weeks was 67% in Group I and unchanged in Groups II and III. In conclusion, laser irradiation and laser welding did not increase the patency rate of microvascular anastomoses done with alcohol preserved homografts. Thrombotic occlusion in microvascular homografts usually occurs before the second week postoperatively. PMID- 1751143 TI - Determinants of measured dialysis venous pressure and its relationship to true intra-access venous pressure. AB - Venous pressure measured at the venous bubble trap (VPdm) is a complex function of true intra-access pressure (VP0), hematocrit, needle gauge, and blood flow. In a patient free circuit, needle gauge, hematocrit, and blood flow influenced the pressure drop through the venous return needle. Measured intra-access pressure (VPm) and VPdm also were determined 149 times in 83 subjects. The increase in VPdm above VP0 under conditions of flow through 16 gauge needles was affected by blood flow rate, hematocrit, and VP0 with coefficients similar to those found in vitro. Calculation of VP0 from VPdm produced an absolute difference greater than 20 mmHg in 35-40% of cases. Mean VP0 was significantly lower in subjects with native compared with expanded polytetrafluorethylene accesses. It was concluded that VP0 is influenced by access type and can be estimated but that direct measurement is preferred. Direct measurement of VP0 may be a sensitive test to screen for venous outlet stenosis because it should vary with access flow and outlet geometry. PMID- 1751144 TI - Transcatheter placement of an intraluminal prosthesis for the thoracic aorta. A new approach to aortic dissections. AB - A new aortic prosthesis (SAP, shape memory aortic prosthesis) was developed with its transfemoral placement system to treat aortic dissection with minimal invasion. The SAP consists of a Nitinol stent and polyurethane tube, and it is designed in such a configuration that it can be compressed inside a 14 Fr catheter when cold. It regains its original shape when warmed to 30 degrees C. From the results of intra-aortic sutureless placement of SAP in 10 mongrel dogs, we concluded that a SAP of proper diameter could be implanted safely for more than 3 months. The transfemoral placement system is composed of a delivery catheter, pushing rod, catching catheter, and pulling wire. Using these devices, transfemoral placement of SAP was demonstrated successfully in three dogs and one sheep. The original SAP and delivery system can be used as an emergency procedure for aortic dissections, such as Stanford type B. The advantages of the procedure are minimal invasion of acutely ill patients and prompt application in the catheter laboratory. PMID- 1751145 TI - Experimental studies on improved polyester-polyurethane vascular grafts for hemodialysis. AB - A new poly(ether-urethane) graft (PEUG) was developed. Although this graft had several advantages, it became clear that it also had disadvantages, such as the formation of pseudoaneurysms by repeated puncture. To overcome these problems, the PEUG was modified to add mechanical strength by incorporating knitted polyester fibers. Physical strength tests were done, and it was concluded that the graft was more durable than either PEUG or expanded polytetrafluorethylene. Additional experiments showed that gelatin coated PEUG implanted in dogs facilitated endothelialization of the internal surface and improved its patency, although these observations were too short to draw any definitive conclusions. PMID- 1751146 TI - Effect of recombinant human erythropoietin on vascular access. AB - The use of recombinant human erythropoietin (r-HuEPO) corrects the anemia of chronic hemodialysis (HD) patients and improves their quality of life. The role of r-HuEPO in the genesis of graft thrombosis is controversial. A retrospective study was conducted of 46 stable chronic HD patients receiving r-HuEPO. It showed an increase in graft thrombosis in those who received the drug. PMID- 1751147 TI - A survey of permanent double lumen catheters in hemodialysis patients. AB - The use of permanent double lumen hemodialysis catheters (PermCath, Quinton, Seattle, WA) was surveyed in 17 dialysis units with a total of 1,372 patients. During the period of study, 210 patients received or already had such catheters. Their use varied widely, being highest in units dialyzing many older patients with associated diseases and difficulties with vascular access. Flow problems occurred in 46% and clotting in 24%; 27% required urokinase (at least once), and 10% received some form of anticoagulation. Local infections occurred in 15% and septicemia (at least once) in 15%. Some older patients elected to continue with this form of "painless" dialysis. PMID- 1751148 TI - Ventricular assist with heparin surface coated devices. AB - Heparin surface coated ventricular assist devices (VADs) were evaluated without systemic heparinization and compared with uncoated control VADs with systemic heparinization (bovine experiments, n = 8; bodyweight, 75 +/- 6 kg). No heparin was given in the study group, whereas heparin (300 IU/kg) was given before cannulation in the control group. Mean activated clotting time (ACT) was 127 +/- 12 sec before and 122 +/- 17 sec after 6 hours of left ventricular assist for coated (NS) versus 184 +/- 114 sec before and 650 +/- 240 sec after for uncoated (p less than 0.05) VADs. No difference was observed in platelet depletion, plasma hemoglobin, lactic dehydrogenase (LDH) production, mixed venous oxygen saturation, and VAD clot score. No VAD occlusions occurred. Ventricular assist can be achieved without systemic heparinization if VADs are improved. PMID- 1751149 TI - Easy access for a left ventricular assist system without thoracotomy. AB - In a previous article, a left ventricular assist system (LVAS) with a percutaneous transseptal cannulation technique for easy application was described. This system was safe and efficient (maximum output greater than 3 L/min) and fitted between the intraaortic balloon pumping and LVAS with thoracotomy. But technical skill for placement was slightly complicated. The cannulation system has been improved. In the new system, the inlet cannula is initially used as a sheath introducer and is quickly inserted into the left atrium after transseptal puncture. The new inlet cannula is made of polyvinyl chloride (TM100, Toyobo, Co., Ltd., Osaka, Japan), which has excellent antithrombogenicity and low friction using a polyester plasticizer. The distal part is designed to be flexible with a spiral wire for easy manipulation. A sealing hub was installed to prevent bleeding at the proximal The simplicity and safety of the new system were examined in chronic animal experiments. The inlet cannula was placed into the left atrium within a few seconds after transseptal puncture. During 20 days of activation, there were no episodes of systemic or pulmonary embolism, although no anticoagulant was used. Under fluoroscopy, there was no thrombus formation around the cannula at removal. On the 14th day after removal, the puncture site of the septum had healed. This system is ready for clinical use and shows promise of satisfactory safety and manageability. PMID- 1751150 TI - Percutaneous cardiopulmonary support in cardiac arrest. AB - Of 11 patients who underwent emergency resuscitation from cardiac arrest using a system of percutaneous cardiopulmonary support (CPS), two (18%) were long-term survivors. Percutaneous cardiopulmonary support was instituted without complication in all patients, with flows ranging from 1.8 to 5.5 L/min; the average duration of support was 304.3 min. All four patients who underwent emergency surgery (two coronary revascularization, one mitral valve revascularization, one mitral valve replacement with coronary revascularization, and one primary left ventricular assist device insertion) died. One patient died while on CPS secondary to irreversible ventricular arrhythmias after a successful percutaneous transluminal coronary angioplasty (PTCA). Six patients were weaned from the support system, three of whom had undergone PTCA while on CPS. The two survivors were the youngest patients (33 and 24 years). One of them had severe hypothyroidism as the cause of cardiac arrest, and the second was a hypothermia patient who was in ventricular fibrillation for 2 hr before establishing CPS. In comparing survivors (two) to nonsurvivors (nine), a significant difference (p = 0.034) in age was found, with survivors being younger. There was also a difference in incidence of atherosclerotic cardiovascular disease (p = 0.018), with survivors having none. There was no difference in the time to CPS (p = 0.905) or time on CPS (p = 0.156). Cardiopulmonary support can be instituted, resulting in excellent stabilization in patients with cardiac arrest. Survivors tended to be young and not have atherosclerotic cardiovascular disease (ASCVD) as their primary diagnosis. Neither length of cardiac arrest before CPS nor time on support correlated with a poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751151 TI - Frequency and significance of infections in patients receiving prolonged LVAD support. AB - Infections in patients undergoing mechanical circulatory support as a bridge to transplant are associated with significant mortality and morbidity. To determine the frequency and effects of infection during such procedures, a retrospective analysis was done of 14 patients who received prolonged (greater than 14 days) support with the Heartmate left ventricular assist device (LVAD) (Thermo Cardiosystems, Inc., Woburn, MA). All patients were men (mean age, 44.3 years), and duration of LVAD support ranged from 19 to 233 days (mean, 98.1 days). During LVAD support, five patients had no infections, and, in the remaining nine patients, infections were most common in the respiratory tract, catheter tips, and urine. Four device related infections occurred in three patients, all of which were resolved with antibiotic therapy. All 14 patients underwent transplantations, and none of the operations was delayed because of infection. Eleven of the patients are long-term survivors (range of time after transplant, 7.5-37 months). Infections were not associated with mortality or significant morbidity in this group of patients. PMID- 1751152 TI - The consequence of ventricular assist on acute profound biventricular failure with induced severe myocardial injury. AB - The effect of ventricular assist on acute profound biventricular failure (BVF) was examined in chronic animal experiments using 10 adult goats. Induction of BVF was achieved by normothermic anoxic arrest for 30-60 min during the use of a left ventricular assist system (LVAS, eight goats), or biventricular assist system (BVAS, two goats). The LVAS could maintain near normal circulation with volume loading in six goats, and three of eight goats were weaned from LVAS after 13-18 days. In the early stages, left atrial pressure was significantly higher, and right atrial pressure was significantly lower, compared with measurements in nonweaned goats. During BVAS, circulation was well maintained without volume loading, but neither of the two goats could be weaned from VAS. Myocardial fibrosis in goats without myocardial recovery was significantly more severe. Left ventricular wall thickness was thinner in nonweaned goats and there was a significant inverse correlation between the thickness of the left ventricular free wall and the assist duration in nonweaned goats. Based on these data, it was concluded that myocardial damage was severe in nonweaned cases, and the potential for healing is affected by the severity of myocardial damage before VAS application. Prolonged unloading with VAS of these severely damaged hearts caused loss of left ventricular wall thickness. PMID- 1751153 TI - Univentricular support results in reduction of pulmonary resistance and improved right ventricular function. AB - A retrospective analysis was performed to assess the effects of univentricular support on the transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and right ventricular ejection fraction (RVEF) in 16 patients who spent from 2 to 144 days (mean, 61) on the Novacor left ventricular assist system ([LVAS] Novacor Corp., Baxter Healthcare, Oakland, CA) as a bridge to cardiac transplantation. Results revealed a significant reduction in the TPR, and improvement in RVEF while patients were on the LVAS. After orthotopic heart transplantation (OHTx), TPG and PVR were significantly lower than when calculated before support. It was concluded, therefore, that the reduction in the TPR and the improvement in the RVEF, seen in patients who were provided univentricular support with the Novacor LVAS, are associated with a significant reduction in the TPG and the PVR, which are persistent after OHTx. Four patients who otherwise would have been considered at higher risk for OHTx because of elevated pulmonary resistance before veniventricular support underwent successful OHTx after LVAS support. PMID- 1751154 TI - A theoretical study of new types of valve shunts for cerebrospinal fluid. AB - Two new solutions for cerebrospinal fluid (CSF) valve shunts are described. The first is based on the principle of multihole flow, and the second, which is less complex mechanically, is based on the action of elastic elements on a ball-cone valve. PMID- 1751155 TI - Catheter with an anchoring tip for chronic joint capsule perfusion. AB - An orthopedic catheter for long-term access to the synovial joint is anchored by a hollow threaded tap that penetrates the capsule through a hole drilled in the surrounding bone. The proximal end of the catheter is connected to either an implantable drug infusion pump or an implantable access port for continuous or intermittent perfusion or sampling. Four catheters were evaluated in dogs. Three were attached to ports, the fourth to a pump. Water (one trial, 22 weeks) and hyaluronic acid (HA) (5 mg/ml; two trials of 8 weeks each) were administered through ports twice weekly in 1.5 ml boluses; 5 mg/ml HA was delivered by pump (1 trial of 33 weeks) at 0.31 ml/day. PMID- 1751156 TI - A protamine-mediated heparin sensing device. AB - A convenient, protamine mediated strip assay for heparin was developed. The assay is established on the specific interaction between heparin and protamine, and the metachromatic color change of methylene blue dye from blue to purple in the presence of heparin. The device consists of a fibrin cup fabricated with a cellulose paper strip containing immobilized protamine. To analyze plasma heparin levels, a fixed volume of the test sample is placed in the fibrin cup and allowed to migrate through the strip in a descending manner until exhaustion. The region to which heparin binds is then visualized as purple in color by spraying methylene blue dye onto the strip. The heparin level in the sample is estimated from the length of the purple region using a preconstructed standard curve. This device proved to be capable of detecting and differentiating heparin in clinically relevant concentrations. PMID- 1751157 TI - Development of an implantable drug delivery catheter. AB - A microtextured, pillared drug delivery system has been designed and tested in rabbits. This model has allowed for the calculation of the mass transport rate indicating after a 4 week time period a pillar device's mass transport rate K1 [min-1] is K1p 1.54 x 10(-2) in contrast to the smooth control which is K1C .043 x 10(-2) and K1im IM which is 0.136 x 10(-2). As a result of these experiments, it is apparent a micropillared drug delivery system is an order magnitude faster than an intramuscular injection and is 30 times faster than the smooth control device. The etiology for this difference is related to close blood vessel proximity and minimal to no fibrous capsule formation with the micropillared implant. Finally, even after a 6-month implantation time, the pillared device has greater reproducibility regarding curve profile and there is no loss in magnitude or rate of mass transport, in contrast the smooth control devices in many instances resulted in complete occlusion with total loss of mass transport capabilities. PMID- 1751158 TI - Prostatic titanium urethral stents. A new treatment option for obstructive uropathy: early clinical results and indications. AB - An expandable titanium stent was used as an alternative to standard treatment for urinary obstruction in 20 men. Six patients had recurrent urethral strictures. Fourteen patients had obstruction secondary to benign prostatic hyperplasia (BPH) and were considered high risk surgical candidates. Complete results with a mean follow-up of 12 months are available for 11 patients. Four of the six stricture patients are currently unobstructed. All seven of the available men with BPH are voiding well. No side effects have been related to the stents, and no encrustations or calculi have formed. PMID- 1751159 TI - In vitro and in vivo evaluation in dogs of a miniaturized glucose sensor. AB - A miniaturized glucose sensor was developed, consisting of a platinum wire entirely coated with teflon, except for a 1 mm section near its extremity where glucose oxidase is immobilized. The in vitro sensitivity to glucose of the sensors was 2.3 +/- 0.4 nA/mM, mean +/- SEM (n = 23). These sensors were implanted in the subcutaneous tissue of normal beagles. Two consecutive glucose infusions (15-30 mg/kg/min) were performed. The current generated by the sensor was used for calculation of the sensitivity coefficient (SC) (nA/mM), and the background current in the absence of glucose (lo) (nA). These parameters were used for determination of the apparent subcutaneous glucose concentration. The in vivo sensitivity was less than the in vitro sensitivity (0.5 +/- 0.1 vs. 2.2 +/- 0.2; n = 12 comparisons; p less than 0.01). Stability of sensor function was demonstrated by the absence in variation of SC and lo, calculated from the different plateaus obtained during the glucose infusions. This study provides a simple method for evaluating in vivo the function of a miniaturized sensor implanted in subcutaneous tissue. PMID- 1751160 TI - An integrated artificial heart-lung device. AB - An integrated artificial heart-lung device (IAHLD) is being developed as a novel system for simultaneous long-term support of heart and lung. The IAHLD consists of an artificial lung component (LC) and two blood pumps. The LC is made with a special composite hollow fiber membrane that prevents serum leakage. The fibers are arranged as piled-up lattices and potted in a cylindrical housing made of polyurethane. The blood pump with a single port is of a pneumatic pusher-plate type, and a Bjork-Shiley valve is mounted in the port. The LC is sandwiched between the inlet and outlet pumps, and all components are integrated. This special structure provides high gas exchange efficiency, prevention of flow channeling and stagnation, and reduction of blood contacting surfaces. The prototype IAHLD had exchange rates of up to 170 ml/min of O2 and CO2 and up to 5.5 L/min of pump output. A flow visualization analysis with cineroentgenography revealed that the flow distribution within the IAHLD was uniform, without any stasis. It was concluded that the IAHLD is a promising system for long-term heart and lung support, and can be used without systemic heparinization given thromboresistant surface treatment as the next step of development. PMID- 1751161 TI - Racial differences in renal transplant outcome of insulin-dependent diabetic recipients in the cyclosporine era. AB - In an attempt to analyze the influence of race on renal allograft outcome among insulin-dependent diabetic uremics, all 109 cyclosporine treated transplants were studied. Black recipients were noted to have inferior 1 year survival for both living related and cadaver donor grafts when compared with both whites and Hispanics (67% and 43% vs. 92% and 84%, 100% and 80%, respectively, p less than 0.01). Nonimmunologic causes accounted for 69% of graft losses among blacks, compared with 39% and 33% in whites and Hispanics, respectively. Among long-term survivors, however, renal function remained relatively stable among all racial groups. This differing trend among black diabetic recipients suggests the need for aggressive cardiac workups before transplantation, and judicious immunosuppression in the posttransplant period. PMID- 1751162 TI - Neoendothelial healing of modified EPTFE grafts. AB - Expanded polytetrafluoroethylene (EPTFE) grafts have poor neoendothelial healing characteristics and low patency rates after long-term implantation. The authors have shown that this is due to the low porosity of currently used EPTFE grafts (20-30 microns fibril length). The inner surface coated grafts made of long antithrombogenic material fibrils (40-60 microns) are desirable, especially for small diameter grafts. The authors have implanted these surface modified grafts (coated grafts) and noncoated grafts into abdominal arteries of rats and observed good patency rates, and the effects of surface modification of the grafts on stable endothelial tissue growth. The authors used four different kinds of grafts (fibril length, 20, 40, 60, and 90 microns, respectively) to investigate the effect of porosity. High porosity (long fibril length) grafts induce good neoendothelial healing and collagen production. PMID- 1751164 TI - Serum silicon levels in recipients of an electrohydraulic ventricular assist system. AB - This study was designed to determine the permeation rate of silicon oil from the authors' electrohydraulic ventricular assist system (EHVAS), and to evaluate influences on organ function. The permeation rate through the diaphragm of the EHVAS was determined by in vitro experiments. Influences on organ function were evaluated in three goats with EHVAS by monitoring blood chemical parameters and serum silicon levels (S-Si). The permeation rate from the EHVAS was about 0.2 ml/month, calculated from the data obtained in the in vitro experiments. S-Si levels did not increase during chronic animal implantation, and renal and hepatic function were not affected. The permeation rate through the diaphragm must, however, be taken into consideration. PMID- 1751163 TI - Hemostatic evaluation of Sarns/3M-VAD implantation in calves. AB - The authors evaluated the potential for thrombotic complications arising from implantation of a ventricular assist device (Sarns/3M-VAD) in four calves. Coagulation screening tests (prothrombin time [PT], partial thromboplastin time [PTT], thrombin time [TT]), fibrinogen levels, and antithrombin III functional activity were found to be of little value as predictors of the degree of activation of the hemostatic system. However, platelet counts, adenosine diphosphate (ADP)- and collagen-induced platelet aggregation, and thromboxane (TXB2) levels were good indicators of changes in platelet reactivity. Platelet counts (initial value 6 x 10(5) rose, and were associated with increased rate and extent of ADP- and collagen-induced platelet aggregation, which remained elevated during the entire 25 day postimplantation period. The first 5 days postimplantation revealed a typical acute inflammatory response, with increased platelet levels, but with TXB2 levels significantly decreased during this period. A monoclonal antibody based bovine D-dimer assay and Western blot studies indicated a small but significant increase in circulating bovine D-dimer, indicating localized fibrin formation and its dissolution. PMID- 1751165 TI - Effects of long-term Novacor artificial heart support on blood rheology. AB - This study presents characteristics of hemorheology for six patients during long term support (85-144 days) on a Novacor left ventricular assist device (LVAD) as a bridge-to-cardiac transplantation. Results indicate that a certain "baseline" rheology can be identified in patients whose support was uneventful. However, in the patients who had one or more neurologic episodes during support, these events were associated with altered hemorheology, including increases in plasma and relative blood viscosity, and red cell rigidity. PMID- 1751166 TI - Bovine pericardial valves. Nine-year clinical experience with the Novacor left ventricular assist system. AB - The Novacor electrically powered left ventricular assist system (LVAS), currently used in a bridge-to-transplant (BTT) clinical trial, incorporates bovine pericardial (BP) valves (Edwards CVS Division, Baxter Healthcare Corporation). In preclinical evaluation in the adult sheep, BP valves exhibited severe calcific stenosis as early as 8 weeks postimplant (longest implant 158 days, elective termination for calcific deposit). The clinical experience, however, has been in sharp contrast. Eighty-one patients have been supported for a cumulative duration of 9.1 years (two currently on LVAS). Thirty-five (43%) patients were supported for longer than 30 days, and of these, 29 (85%) were transplanted. The longest implant duration was 370 days (alive, 8 months posttransplant). There was no evidence of calcific degeneration of these valves for durations to 370 days. These results are encouraging for ultimate chronic clinical application. PMID- 1751167 TI - Pulsatile flow and EC morphology in a VAD-like chamber. PMID- 1751168 TI - Novel airway stent using a thermal shape-memory Ti-Ni alloy. AB - An attempt was made to develop a tracheal or bronchial stent for nonsurgical implantation using a bronchoscope. Titanium-nickel alloy composed of 50% by weight of each metal has unique thermal shape-memory properties, with a transition temperature of 20 degrees C. Each stent consists of one wire with a diameter of 0.9 mm. It is 30 mm long with a cross-sectional profile resembling a horseshoe. The stent is designed to sustain the airway only at the cartilage rings. Tracheal cartilages of dogs were broken to make a tracheomalasia model, and 10 stents were implanted in 10 animals. The stents were made straight by cooling in liquid nitrogen and then inserted into the region of tracheomalasia. Once in place, they were warmed and recovered their initial shape. The animals were killed between 1 week and 6 months after implantation, and then examined. Nine of the ten stents were located in the implanted area. In one dog, the stent had been displaced into the bifurcation. Microscopic observation showed that the wires were gradually covered with epithelium. At 6 months, 58% were covered with epithelium. PMID- 1751169 TI - Tumor necrosis factor clearances during veno-venous hemodiafiltration in the critically ill. AB - Tumor necrosis factor alpha (TNF) is a mediator of injury in the critically ill. Its small molecular size (17 kd) should allow its clearance during continuous hemodiafiltration (CHD). The authors studied TNF extraction in 12 critically ill patients (APACHE II score 26.3 mean; range, 19-34) receiving CHD. Tumor necrosis factor levels were measured in prefiltered and filtered blood and ultradiafiltrate at 0.4 and 24 hours of therapy. Before CHD, mean plasma TNF levels were 261 pg/ml (95% confidence interval [CI]: 184-578) and 291 pg/ml (95% CI: 0-589) after 24 hours. There were no statistically significant differences between prefilter and postfilter TNF levels. Most ultradiafiltrate samples (74%) contained demonstrable TNF (mean, 314 pg/ml; 95% CI: 67-561). Daily TNF excretion was a mean of 15.9 micrograms (+5.6 standard error [SE]), with a mean daily clearance of 27.5 L (95% CI: 2.5-52.5). The authors conclude that significant amounts of TNF are excreted in the ultradiafiltrate during CHD. This observation may provide a rationale for use of similar therapies in critically ill patients in the absence of conventional indications for dialytic support. PMID- 1751170 TI - In vivo catecholamine extraction during continuous hemodiafiltration in inotrope dependent patients. AB - Many critically ill patients require inotropic or vasopressor support to maintain adequate oxygen delivery. Removal of catecholamines by continuous hemodiafiltration (CHD) could alter exogenous catecholamine requirements. The authors have studied hemodynamic state, catecholamine clearances, and catecholamine requirements in 12 critically ill patients (mean APACHE II score, 24.5) receiving CHD. Hemodynamic parameters were assessed before CHD initiation, and at 4 and 24 hours of therapy. Simultaneous determinations of serum and ultradiafiltrate dopamine (D), norepinephrine (NE), and epinephrine (E) concentrations were obtained. There were no significant changes in any of many hemodynamic parameters measured during CHD. Mean catecholamine requirements were not altered by CHD. Plasma catecholamine levels were not significantly affected by CHD (mean values at 0, 4, and 24 hours: D: 10,801, 12,056, and 8,797 pg/ml; NE: 1124, 566, and 926 pg/ml; E: 1,420, 1,383, and 843 pg/ml). Catecholamine clearances from CHD (D:43.7 ml/min; NE: 43.5 ml/min; and E: 46.6 ml/min) resulted in daily excretion of only 379 micrograms D, 32.9 micrograms NE, and 37.2 micrograms E. Clearances of catecholamines by CHD represented a daily loss of less than 0.1% of the administered load. In conclusion, although CHD can remove circulating catecholamines, cumulative daily catecholamine extraction is minimal in pharmacologic terms, and has no impact on hemodynamic status. PMID- 1751171 TI - A new treatment strategy using both intermittent short dialysis and continuous ambulatory hemofiltration. AB - The authors devised a new treatment strategy using continuous ambulatory hemofiltration (CAHF) in between short hemodialyses (short HD). For CAHF, a small wearable hemofilter (0.1 m2) was developed using a membrane permeable to low molecular weight proteins. During short HD, no body water was removed, but saline, equivalent to 3% body weight, was administered at a constant rate. During CAHF, 1 L of replacement fluid was administered intravenously after every meal to increase the replacement volume. Switch from the conventional to new strategy resulted in far more stable blood pressure during short HD, a decrease in time averaged body weight, and a decrease in a decrease in time averaged blood urea nitrogen and plasma beta 2-m levels. PMID- 1751172 TI - Microencapsulated hepatocytes. Prospects for extracorporeal liver support. AB - To assess the potential for encapsulated hepatocytes as a bioartificial liver support system, rabbit hepatocytes were encapsulated within multicomponent capsules using a complex coacervation technique, and cultured both on plates and in a perfusion reactor. The urea synthesis rate and antipyrine and diazepam degradation rates were evaluated in each system over a 10 day period, and compared with standard plate-cultured hepatocyte efficacy. Urea synthesis rates were significantly higher in the perfusion cultures than in either of the plate culture environments, whereas drug degradation rates were not significantly different in any of the systems. PMID- 1751173 TI - Blood purification for postoperative liver failure with special reference to chronic hepatic support for those awaiting liver transplantation. AB - Blood purification, mainly plasma exchange (PE), was carried out for 13 cases of acute, and two cases of chronic postoperative liver failure. Four of thirteen acute cases (31%) survived. Although only one of eight with chronic liver disease survived, three of five without chronic liver disease survived. In most of those who lived, other organ failure occurred less often; total bilirubin and blood ammonia were less than 15 mg/dl and 200 micrograms/dl, respectively, before PE: and total bilirubin, blood ammonia, and branched chain amino acid/aromatic amino acid (BCAA/AAA) ratios recovered after five or fewer sessions of PE. Two chronic cases, treated for 1 and 4 years, respectively, were good candidates for liver or multiple organ transplantation. Although both died, PE was effective in reducing jaundice and in improving consciousness and general condition. Plasma exchange should be introduced early after assessing the changes in total bilirubin, blood ammonia, and coma grade in patients with acute postoperative liver failure. Plasma exchange could be useful as a chronic hepatic support system for those awaiting liver transplantation. PMID- 1751174 TI - Neurologic improvement of patients with hepatic failure and coma during sorbent suspension dialysis. AB - Fifteen patients with acute deterioration of liver function, high serum ammonia, and an average coma level of 3.9 (of 4) were treated for 8-12 hrs daily with a system that uses the membranes of a cellulosic plate dialyzer to pump blood through a single access at 200-225 ml/min, and includes a sorbent suspension as dialysate. Neurologic status of the patients was declining before treatment, but significantly improved during each treatment and over the course of 1-12 (average, 4) treatments. Diastolic blood pressure and pulse rate normalized. For half the patients, treatment with the BioLogic-DT system served as a bridge to liver transplant or liver recovery. PMID- 1751175 TI - A hybrid artificial liver system. Function of cultured monolayer pig hepatocytes in plasma from hepatic failure patients. AB - To produce a new hybrid artificial liver system, cultured pig hepatocytes were used in this study. Hepatocytes from normal healthy pigs were cultured in multiwell dishes. From the third day of cultivation, hepatocytes were divided into three groups according to the media used (Group 1, L-15; Group 2, normal human plasma; Group 3, plasma from hepatic failure [HF] patients). Measurements of cellular function of the cultured pig hepatocytes included metabolic activity (gluconeogenesis and ureogenesis), DNA content, and amino acid changes in the plasma. The ability to provide gluconeogenesis and ureogenesis by the cultured hepatocytes in HF plasma was maintained for 3 days, equal to that observed in Groups 1 and 2. DNA content was no different in the three groups. Elevated amino acid levels in the HF plasma, Phe, Met, Lys, and Gly, were significantly reduced by the cultured hepatocytes. The results indicate that the use of primary cultured pig hepatocytes is a step toward a hybrid artificial liver system, and a promising candidate as a bioreactor. PMID- 1751176 TI - Management of postoperative biventricular failure by means of a right ventricular assist device and an intraaortic balloon pump. AB - Right dominant biventricular failure often accompanies the end-stage of combined rheumatic valvular disease and some kinds of congenital heart disease. The management of right ventricular failure with conventional medical treatment, however, has encountered many difficulties. Mechanical support of the right ventricle with an RVAD (right ventricular assist device) has proved useful and effective. Seven patients who could not be weaned from cardiopulmonary bypass were subsequently transferred to an intraaortic balloon pump (IABP) and RVAD. Among these, five had severe combined rheumatic valvular disease, one had congenital heart disease and was advanced in age, and the other had a left atrial myxoma with tricuspid regurgitation. Preoperatively, all of these patients had had biventricular failure. All seven cases were successfully weaned from RVAD, and later from IABP. Five patients were discharged from the hospital and returned to normal daily life. Two patients died during their postoperative course. Long term survival rate was 71%. Mechanical assist with RVAD and IABP seemed to be effective in the management of right dominant biventricular failure, such as that seen in combined valvular disease and some kinds of congenital heart disease. PMID- 1751177 TI - Experience and directions using cardiopulmonary support in fifty-three consecutive cases. AB - Emergency cardiopulmonary support (CPS) was instituted in 53 consecutive patients for acute life threatening pathologies. Indications for CPS deployment were: cardiac arrest, 60% (n = 32); cardiogenic shock, 20.4% (n = 11), supported angioplasty, 13% (n = 7); and adult respiratory distress syndrome, 5.6% (n = 3). Cardiopulmonary support was successfully deployed in 51 of the 53 patients (96%), resulting in a mean blood pressure greater than or equal to 60 mmHg, CO greater than or equal to 3-5 L/min, and partial pressure of oxygen greater than or equal to 100 mmHg, with venous oxygen saturation greater than or equal to 60%. The average time from arrest to CPS deployment was 40 minutes. Seventy-nine major cardiovascular procedures were done in these 51 patients (average, 1.5/patient). The duration of support ranged from 1 to 75 hrs (mean, 16.1 hrs). Twenty-seven patients (53%) were weaned, 13 successfully (32%), with 11 (85%) surviving greater than 24 hrs, and six (46%), greater than 30 days. The other 24 patients (47%) were transferred to other treatment modalities, including cardiac surgery and bridge-to-transplant ventricular assist devices. Four of these patients died (17%), whereas 20 (83%) survived. Of these survivors, 19 (95%) survived greater than 24 hrs, whereas 11 (55%) survived greater than 30 days. The overall survival using the CPS system is 59% short-term (greater than 24 hrs.), and 33% long-term (greater than 30 days). In conclusion, the CPS system is a potent and effective resuscitative tool. It requires transfer to other treatment modalities for survival in most cases. PMID- 1751178 TI - Comparison of an extraaortic counterpulsation device versus intraaortic balloon pumping in severe cardiac failure. AB - A valveless, single orifice polyurethane ventricle was implanted on the brachiocephalic artery in sheep (n = 14) to provide extraaortic counterpulsation. In parallel, an intraaortic balloon was placed in the descending thoracic aorta. Both devices were pneumatically driven by a standard intraaortic balloon pump (IABP) console at a preload of 40 cc. Severe cardiac failure was induced with high dosages of esmolol. Measured parameters were aortic pressure (PA) and flow (QA), coronary flow (QC), and left ventricular pressure (PLV). Tension time index (TTI), total QA and QC, and end-diastolic aortic pressure (EDP) were computed to compare the efficacy of counterpulsation between assisted and unassisted conditions. Three conditions of inflation/deflation timing were examined: Normal timing (NT), early inflation (EI), and late deflation (LD). Results indicated that extraaortic counterpulsation device actuation yielded statistically significant increases in QC, and significant decreases in EDP and TTI for all timing conditions examined, when compared with unassisted conditions. Flow was significantly increased only for EI and NT timing conditions. Counterpulsation delivered with IABP yielded statistically significant increases in EDP for LD timing, and significant decreases in TTI for NT only. These results indicate that EACD is much less dependent on inflation/deflation timing when compared with IABP. The extraaortic counterpulsation device consistently increases QC and decreases TTI, which enhances the oxygen supply/consumption ratio (S/C) of the left ventricle. The intraaortic balloon pump does not significantly increase S/C in severe cardiac failure, and will increase afterload if deflation timing is not properly set. PMID- 1751179 TI - Recovery of end-stage organ dysfunction by circulatory assist. AB - To clarify the effectiveness of left ventricular assist on recovery of critical organ dysfunction, 18 patients with ventricular septal rupture or free wall rupture after acute myocardial infarction were retrospectively studied. Fifteen patients were managed with an intraaortic balloon pump (IABP group), and three with a left ventricular assist device (LVAD group) after surgery. In the IABP group, nine patients survived and six died. There were no significant differences between survivors and nonsurvivors with respect to age, cardiopulmonary bypass time, or preoperative renal function. In addition, there were no significant differences in the early postoperative changes in cardiac index. Larger doses of catecholamines were required in nonsurvivors than in survivors, however; blood urea nitrogen and creatinine levels were significantly higher in nonsurvivors than in survivors, and the nonsurvivors' creatinine clearance values stayed under 20 ml/min during the postoperative course, so that all nonsurvivors required renal assist. All in the LVAD group were weaned. Two patients were lost, however, because of cardiac arrythmia and massive gas embolism. Cardiac index in the LVAD was maintained at over 2.1 L/min/m2 with a minimum dose of catecholamines, regardless of poor left ventricular function, and creatinine clearance recovered to over 20 ml/min during circulatory assist. From these data, high doses of catecholamines depressed renal function after surgery. Therefore, it has been concluded that the major role of circulatory assist is to maintain more of the physiologic circulation with minimum doses of drugs. PMID- 1751180 TI - Mean velocities and Reynolds stresses within regurgitant jets produced by tilting disc valves. AB - Fluid velocities were measured with a two-component laser Doppler anemometry system in the regurgitant jet regions of Bjork-Shiley Delrin monostrut tilting disc valves mounted within a Plexiglas model of the 70 cm3 Penn State electric left ventricular assist device. At each measurement location, 250 instantaneous velocity realizations were collected at times when regurgitation through the valves occurred. The maximum Reynolds shear and normal stresses were calculated after filtering the data. Results show that Reynolds shear and normal stresses proximal to the mitral valve were elevated to magnitudes of 9,000 dynes/cm2 and 20,000 dynes/cm2, respectively. The peak Reynolds stresses near the mitral valve occurred during early systole, when regurgitant jet velocities reached magnitudes as high as 440 cm/sec. The Reynolds shear and normal stresses proximal to the aortic valve reached magnitudes of 9,900 dynes/cm2 and 20,500 dynes/cm2, respectively. The peak Reynolds stresses near the aortic valve occurred during early diastole, when regurgitant jet velocities were as high as 280 cm/sec. These high Reynolds stresses created by turbulent regurgitant flow have the potential to cause significant blood damage. PMID- 1751181 TI - Two-dimensional mechanical and ultrastructural correlates of bovine pericardium for prosthetic valves. AB - Scanning electron microscopy of bovine pericardium (BP) shows anisotropic collagen fiber orientation (CFO). We studied the effect of CFO on the breaking strength of longitudinal (L) and transverse (T) strips cut from six pieces of fresh (Fr), glutaraldehyde (Glu)-, or formaldehyde (For)-fixed BP loaded at constant rate until rupture. Maximum tensile stress (Stmax) and strain (Snmax) were measured. The Stmax of L strips were larger than T ones in all groups, and Snmax was the same. Similar results were also observed in 10 pieces of Glu fixed normal canine mitral valves (MV). Maximum tensile stress is obtained when the load is parallel to CFO in both canine MV and BP. PMID- 1751182 TI - Real-time in vitro observation of cavitation in a prosthetic heart valve. AB - A technique for real-time in vitro observation of cavitation on a prosthetic heart valve operating in a ventricular assist device under normal physiologic conditions has been developed. Considering the documented observation of cavitation erosion in heart valve components from human explants, and the potential risk of blood damage that cavitation presents, the technique developed in this study may prove useful in the design of prosthetic heart valves and ventricular assist devices. Cavitation of a glycerol blood analog fluid has been documented for a Medtronic/Hall prosthetic heart valve operating in a Penn State Electric Ventricular Assist Device. The ventricular assist device was operated in a mock circulatory system under normal physiologic conditions. The valve was located in the mitral position, with the cavitation occurring on the inlet side after valve closure. Bubble cavitation was seen on the valve occluder face, and vortex cavitation was observed at two locations in the vicinity of the valve occluder and housing. The cavity growth and collapse cycle for these forms of vaporous cavitation was less than 1 msec. Stroboscopic photography and stroboscopic videography with frame grabbing were used to document the cavity life cycle. With beat rate held constant, the cavity duration time was found to decrease with increasing mean venous return pressure. PMID- 1751183 TI - Evaluation of a stented polyurethane mitral valve prosthesis. AB - In the search for the perfect valve prosthesis, polyurethane has been used for its excellent physical properties, but thrombosis and embolism have been real problems. The authors investigated the performance and durability of a 23 mm vacuum formed polyurethane Tricuspid Semilunar Valve, in the mitral position. The valve was implanted in eight sheep using standard cardiopulmonary bypass and intermittent aortic cross clamping. Two early failures were due to valve tears. After modification of the manufacturing process, six further valves were implanted in six sheep. All were anticoagulated with warfarin. The valves were calcified on echocardiography and had increasing transvalvular gradients beginning 3 months postoperatively. All six survived and were killed 1-2.5 years after implantation. Despite gross calcification of the leaflets, medium-term function was good. Careful serial sections of brain showed no evidence of thromboembolism. Both kidneys contained small calcium emboli, but no evidence of infarction. Despite calcification, with good medium-term function and no cerebral emboli, this valve may find application in temporary cardiac assist devices. PMID- 1751184 TI - The correlation between improved cellular viability and clinical performance in 5,000 cryopreserved human heart valves. AB - This study analyzes the 5 year, clinical performance of 5,000 recorded implants of cryopreserved human heart valves. Successive changes in the processing methods have increased cell viability to 88% of control data. Data show that increased cell viability correlates with improved clinical performance. The 79 reported removals at 5 years gave an actuarial survival estimate for all reoperations and complications of 97%. PMID- 1751185 TI - Venturi pressure cannot cause cavitation in mechanical heart valve prostheses. AB - Surface pitting of certain mechanical heart valve (MHV) explants has prompted investigation into possible causes of cavitation during MHV operation. Leaflets of a 29 mm MHV were glued shut with B-datum (BD) gaps fixed at 0.0089, 0.0174, and 0.0219 cm. Each BD gap setting was tested in a steady flow chamber, with leakage flow established at transvalvular pressures (delta P) of 20 to 200 mmHg. Laser Doppler velocimeter (LDV) velocity measurements were recorded 220 microns distal to the BD, along with leakage flowrates. Maximum LDV velocities were compared with those calculated using the mass conservation equation. At identical P, the LDV flow velocities for the three BD settings were found to be approximately equal. This indicates a geometric independence of the leakage flow velocity. At atmospheric pressure, the local velocity necessary to cavitate blood as a liquid is approximately 13 m/sec. These results demonstrate that the leakage velocity is insufficient to cause cavitation. A simplified theoretical model is proposed to illustrate the necessary delta P to produce Venturi related cavitation. PMID- 1751186 TI - Real time sound spectral analysis for early detection of thrombosed Bjork-Shiley standard disc valves. AB - Clinical usefulness of sound spectral analysis (SSA) in early detection of thrombosed Bjork-Shiley standard tilting disc prostheses (B-SP) was evaluated. Among a total of 365 B-SP, nine valves developed thrombosis. These included seven MVR and two AVR, and replacement of the affected valves was performed in all cases. Thrombus formation was localized at the minor strut in two cases in which the SSA demonstrated preoperative abnormalities of only opening clicks. In four cases, thrombus formation was noted at both minor and major struts, and the SSA showed abnormalities both on opening and closing clicks. In two cases with pannus formation, no abnormalities were found by SSA. As the thrombi were seen on the minor strut during surgery in all cases with thrombosed valves, the minor strut is considered as the preferred, and probably initial area of thrombus formation, and the diagnosis therefore could be made by abnormal findings on opening clicks. In conclusion, the SSA was found to be a useful diagnostic tool for early detection of thrombosis of B-SP, because the opening clicks of the tilting disc valves were often too low in amplitude for abnormalities to be detected by auscultation. PMID- 1751187 TI - Effects of Hemopump support on left ventricular unloading and coronary blood flow. AB - The effects of the Hemopump (HP) on left ventricular (LV) and coronary hemodynamics, with and without myocardial ischemia, were studied in an acute, anesthetized, open-chest dog preparation (n = 6). Coronary blood flow velocity in the left circumflex was assessed with an intracoronary Doppler catheter. Measurements were made at two pump speeds (minimal = HP1 and maximal = HP7) before coronary ligation (control), after ligation of the LAD (ischemia), and after induction of cardiac failure by multiple ligations of the diagonal branches (failure). Changing from HP1 to HP7 resulted in 1) Increased total cardiac output in ischemia and failure; 2) Increased mean aortic pressure and systemic vascular resistance in control, ischemia, and failure; 3) Decreased LV external work (LV systolic pressure X stroke volume) in control, ischemia, and failure; 4) Decreased LV end diastolic pressure in ischemia; 5) Decreased LV systolic pressure and pressure-rate product in failure; and 6) Increased coronary blood flow/O2 demand ratio in failure. Hemopump support reduced O2 demand by LV decompression, and improved blood flow/O2 demand ratio in the nonoccluded coronaries of ischemic, failing hearts. PMID- 1751188 TI - Effect of synchronous and asynchronous pulsatile flow during left, right, and biventricular bypass. AB - Ventricular assist devices augment aortic or pulmonary flow while the patient's heart recovers from surgery or infarction. Most are used in the asynchronous full to-empty mode, but they also may be used in a synchronous counter-pulsation mode. This study examines which assist mode optimally reduces myocardial oxygen consumption (MVO2). Eighteen pigs were instrumented with pulmonary artery, carotid artery, and coronary sinus catheters for determination of MVO2. Pierce Donachy Ventricular Assist Devices (VAD) were used in left, right, or biventricular assist mode. Fifteen minute periods each of control, synchronous, and asynchronous bypass were randomly instituted. The mid-left anterior descending coronary artery was then ligated, and the sequence repeated. At the end of each period, MVO2 was determined. In comparison with controls, MVO2 was statistically significant in the BIVAD asynchronous mode only. Synchronized counterpulsation did not decrease MVO2. When ventricular assist devices are used to aid in cardiac recovery postoperatively or postmyocardial infarction, biventricular assist should be used. PMID- 1751189 TI - Peripheral circulation during nonpulsatile systemic perfusion in chronic awake animals. AB - Peripheral circulation (PC) during nonpulsatile (NP) perfusion is not satisfactorily understood, although it is known that animals can survive with chronic NP flow. In awake goats, PC was analyzed by hemodynamic and hormonal parameters, tissue blood flow of the ear measured by a noninvasive laser Doppler flowmeter, and distribution of the body surface temperature monitored by thermography. An NP systemic circulation was established in five 40-64 kg goats with a centrifugal pump (MD-10, Iwaki Pump, Japan) that replaced a pulsatile ventricular assist device 2 weeks postoperatively; this was done without anesthesia. Nonpulsatile total left heart bypass was obtained, with flow rates of 78-165 ml/kg/min. Systemic vascular resistance and blood adrenalin and noradrenalin levels were not affected by the depulsation. Tissue blood flow during NP perfusion was well maintained and showed comparable values to those during pulsatile systemic circulation. Vasomotion of 10-20 cycles/min was obvious in the tissue blood flow pattern, indicating adequate PC at each sampling point. Thermography before and after depulsation indicated no change of temperature distribution, and displayed warm peripheral areas. In conclusion, PC of animals on chronic NP systemic perfusion is adequately maintained. PMID- 1751190 TI - Percutaneous transluminal coronary angioplasty with hemoperfusion. AB - Balloon inflation time during percutaneous transluminal coronary angioplasty (PTCA) is limited by the patient's tolerance to ischemia. A nonpulsatile, variable flow rate syringe pump that develops pressures up to 200 psi has been developed, along with PTCA catheters capable of delivering 0-70 cc/min of blood across a lesion at these pressures. Using this system, 110 patients have been treated with active hemoperfusion during routine PTCA. In eight cases, no preperfusion tolerated inflation time was obtained. In 96 of 102 cases, the tolerated inflation time was increased by at least 50%, for a success rate of 94%. This study demonstrated that active hemoperfusion during PTCA prolongs tolerated inflation time. The catheters and pump are capable of performing routine PTCA, supported when necessary by active hemoperfusion. PMID- 1751191 TI - Outcome of cardiopulmonary resuscitation in patients on chronic dialysis. AB - The authors analyzed the outcome of 56 episodes of cardiopulmonary resuscitation (CPR) in dialysis patients. Eleven patients (20%) left the hospital alive. Univariate analysis showed that a functional cause of cardiac arrest, absence of rib fractures, and the occurrence of cardiac arrest in the dialysis or intensive care units were associated with a favorable outcome. Logistic regression showed that the outcome of CPR was related to the presence of rib fractures, cause of arrest, degree of preexisting heart disease, and patient age. Despite the high incidence of rib fractures (77%), the outcome of CPR in dialysis patients is similar to its outcome in the general population. PMID- 1751192 TI - Sensory perception in uremic patients. AB - Peripheral (PNS) and central (CNS) sensory nervous system function was quantitatively assessed using neuroselective transcutaneous electrical nerve stimulation (TENS) in a population of 19 chronic hemodialysis patients (ages 17 77, median 47 years; duration 1-14, median 3 years). Cutaneous current perception threshold (CPT) provided an index of PNS integrity, and a new technique involving cranial TENS to characterize cephalic evoked noncutaneous sensations (CENS) was used to assess CNS sensory function. Patients showed both CPT (32%) and CENS (89%) abnormalities as compared with previously tested healthy subjects. No significant correlation was observed between age, duration of dialysis, PNS, and CNS abnormalities. The CPT examination provides a sensitive and easy to administer test of PNS sensory function for the purpose of assessing the adequacy of dialysis in chronic hemodialysis patients; the CENS examination also may prove useful in this regard. PMID- 1751193 TI - Optimal dialysate bicarbonate during hemodialysis. AB - Eleven stable hemodialysis patients were treated with acetate dialysate, then changed to bicarbonate dialysate at three different concentrations. Blood was drawn from the arterial limb of the arteriovenous fistula before and after dialysis for pH, partial pressure of carbon dioxide, bicarbonate radical, and partial pressure of oxygen. Both acetate (35 mEq/L) and the lowest bicarbonate concentration (25 mEq/L) resulted in inadequate control of acid-base balance. Using a bicarbonate concentration of 30 mEq/L, mild predialysis acidosis was still present; this could be abolished using 35 mEq/L, but only at the cost of postdialysis alkalosis and mild hypoxemia. PMID- 1751194 TI - Intradialytic parenteral nutrition in chronic hemodialysis patients. AB - The effects of intradialytic parenteral nutrition (IDPN) were studied in chronic hemodialysis (CHD) patients who had a normalized protein catabolic rate (PCRN) of less than or equal to 0.8 g/kg/day, and KT/V = 0.94 +/- 0.04. Intradialytic parenteral nutrition was administered during thrice weekly CHD for 3-6 months, and consisted of essential and nonessential amino acids (42.5 g), glucose (125 g), and lipid emulsion (50 g). Blood urea nitrogen, creatinine, total protein, albumin, transferrin, pre-albumin, total lymphocyte count, anthropometrics, protein catabolic rate, 3 day historic dietary protein intake, and dietary energy intake (DEI) were measured at baseline, before IDPN, during IDPN, and at completion of IDPN. Six of nine enrolled patients completed the study. Reasons for withdrawal included nausea and hyperglycemia or hypoglycemia. DPI normalized for body weight (DPIN) increased significantly from 0.75 +/- 0.1 to 1.02 +/- 0.18 (p = 0.02). Increases in PCRN (0.57 +/- 0.18 to 0.78 +/- 0.2) and DEI (1495 +/- 266 to 1681 +/- 358) did not reach statistical significance. More aggressive IDPN or a longer study period may be necessary to assess this form of nutritional intervention. PMID- 1751195 TI - The effect of ultrafiltration on dialysance. Mathematical theory and experimental verification. AB - It is known that convective transport (ultrafiltration, QF) augments diffusive transport. This augmentation achieves great importance as solute molecular weight increases. Previous mathematical treatments of dialysance (D) have provided the relationship between D and blood flow rate (QB), dialysate flow rate (QD), and dialyzer membrane surface area permeability product (KoA), in the limit of QF = 0. The authors derived the relationship between D (defined as D') and QB, QD, and KoA for the general case of QF greater than or equal to 0: D' = X-Y/In X/Y . [(1 o) QF + KoA] for X = X(D', QF, QD) = 1 - [D'/QD + QF] Y = Y(D', QF, QB) = D' QB/QF-QB o = the Staverman reflection coefficient. This equation demonstrates an approximate linear increase in D' as QF increases. Experimental verification is provided by in vivo studies of dialysis patients in which the dialysance of vancomycin doubles as QF is increased from 0 to 50. Because D' varies linearly with QF, this allows for the determination of KoA and o. Using the Cobe 500HG Hemophan membrane, KoA for vancomycin was determined to be 6.54 and o = 0.88. PMID- 1751196 TI - Behavioral and biochemical indices of compliance in hemodialysis patients. AB - Noncompliance has been implicated in modifying morbidity and mortality in end stage renal disease patients; however, the data are conflicting, and measurement of compliance has been difficult. Traditional measurements of compliance include serum potassium (K) and phosphorus (P) concentrations, and interdialytic fluctuations in weight gain (IWG). This study correlated three indices: 1) Adequacy of dialysis (Kt/V); 2) protein ingestion (PCR); and 3) the percentage of time dialyzed compared with the total dialysis time prescribed (% Time) with the traditional measurements of compliance. Correlations were calculated among pre- and post-BUN (blood urea nitrogen), Kt/V, K and P, PCR, IWG, and % Time. As expected, BUN levels correlated with Kt/V, K, P, PCR, IWG, and % Time. Protein ingestion correlated with K and IWG, but not with % Time. Adequacy of dialysis correlated with P levels, but not with PCR, WG, or % Time. Phosphorus correlated with pre- and post-BUN, Kt/V, and % Time, but not with K. Potassium, P, and IWG did not correlate internally. The authors conclude that standard biochemical measures of compliance reflect different compliance behaviors (dietary selection and restriction, restriction of fluid and salt intake, and adherence to medication regimens). Percent time may be a powerful, independent measure of patient compliance with the dialysis regimen. PMID- 1751197 TI - Clinical effects of recombinant human erythropoietin in hemodialysis patients. Results of the "Abruzzo" Multicenter Trial. AB - Anemia in regular dialysis treatment (RDT) patients is primarily due to a deficiency in renal-derived recombinant human erythropoietin (EPO). The aim of this study was to evaluate the results of a multicenter trial in 81 end-stage renal disease (ESRD) patients on RDT. An "open" study was conducted over 2 years; starting dose of r-HuEPO was 50 IU/kg/three times weekly i.v. and eventually was increased in steps of 25 Ul/kg/dialysis until 300 Ul/kg/week. Mean weekly dose per patient was 15 Ul/kg, with mean Hb increase of 27.5%. Mean hematocrit (Hct) levels increased in these patients from 22.9 +/- 2.5 to 31.7 +/- 2.8 (p less than 0.001) after 2 years of therapy. Both spontaneous and evoked potentials improved. The response to r-HuEPO is dose dependent; hypertension and hyperkalemia are the most common side effects, but they are easily controlled. Central nervous system function before and after treatment is improved, and seems consistent with an enhancement of patients' quality of life. PMID- 1751198 TI - Component selection to optimize blood flow for continuous arteriovenous hemofiltration and dialysis. AB - Blood flow with an arteriovenous access is limited by the resistance of the catheters and hemofilters or dialyzers in the extracorporeal system. Resistance data from manufacturers are varied as to the test conditions used, however, making it difficult to select optimum components. Furthermore, the same size catheters may have varying inner diameters, resulting in large differences in flow resistance. The pressure at various flow rates was determined using a water manometer. The pressure/flow relationship for catheters gave a curve, whereas the logarithmic function resulted in a straight line with a slope of 1.48. The pressure/flow relationship for hemofilters and dialyzers was a straight line with an intercept close to the origin. The data in the tables for flow resistance at 50 and 100 ml/min can be used to compare the various components, and to estimate flow in a given extracorporeal system. PMID- 1751199 TI - Endothelin and platelet activating factor. Possible indices for biocompatibility of hemodialysis. AB - To clarify the roles of endothelin (ET: vasoconstrictor) and platelet activating factor (PAF: vasodilator) in hemodialysis (HD), intradialytic changes in those substances were compared by a crossover study between HD with regenerated cellulose (RC) and polymethylmethacrylate (PMMA) membranes using currently developed radioimmunoassay methods. Hemodialysis patients demonstrated higher plasma ET values than normal controls, and hypertensive HD cases showed the highest levels. Although ET decreased significantly during the initial stage of HD with both membranes, the decreasing rates were greater in the group with intradialytic hypotension than those in the normotensive group. Plasma PAF did not differ among normal controls, hypertensive HD, and normotensive HD patients. Platelet activating factor tended to increase during HD in both hypotensive and normotensive groups; however, the increasing rates were greater in HD with RC than those with PMMA. These results indicate that the decrease in ET may partially contribute to the initiation of HD induced hypotension. Because PAF is an intracellular mediator, and there is an intradialytic increase in PAF with RC membrane, PAF should be regarded as one of the indices of membrane biocompatibility. PMID- 1751200 TI - Evidence of mononuclear cell activation by hemodialysis. AB - The acute effects of hemodialysis (HD) on activation and function of mononuclear cells (MC) were studied in a model of in vitro HD. During the HD session, both cuprophan (CU) and polysulfone (PS) induced transcription of interleukin-2 receptor (IL-2R) mRNA. Expression of IL-2R on the cytoplasmic membrane, and release of soluble IL-2R (sIL-2R), however, did not change during HD, nor did responsiveness to IL-2. Polysulfone caused a slight reduction of the proliferative response to phypohemagglutinin, and of the release of sIL-2R. Hemodialysis did not induce IL-2 production, but induced IL-1 synthesis. PMID- 1751201 TI - Zinc-mediated lymphocyte energy charge modification in dialysis patients. AB - The authors studied the effects of 6 months of zinc therapy on cell-mediated immunity in regular dialysis therapy patients. Serum zinc was significantly enhanced (p less than 0.01) at 2 months. While cells, OKT3, and OKT4 did not show significant variation, but after 6 months of therapy a significant (p less than 0.02) decrease of OKT8 cells, with enhancement of the OKT4/OKT8 ratio, and a significant (p less than 0.01) increase in the Multitest Composite score were found. At the same time, a significant elevation (p less than 0.001) of adenosine triphosphate (ATP), and a reduction (p less than 0.01) of lymphocyte adenosine monophosphate was seen; consequently, energy charge levels increased. Zinc induced improvement of uremic lymphocyte function is likely mediated by an increase in intracellular ATP. PMID- 1751202 TI - Cytokine levels during hemodialysis. AB - The authors measured plasma IL-1 (interleukin-1), IL-2, IL-2 receptor (IL-2R), IL 4, IL-6, tumor necrosis factor (TNF), and granulocyte macrophage colony stimulating factor (GMCSF) in 10 stable patients during hemodialysis (HD) using new or reused polyacrylonitrile (PAN) or cuprophan (CU) dialyzers. Five HD patients with wasting syndrome, and 16 normal controls, were included. Hemodialysis patients showed a marked elevation of IL-2R. No IL-4, IL-6, or GMCSF were detected in any group. Tumor necrosis factor and IL-2 in the HD group were comparable with control values. No difference was found in the TNF levels in HD patients with and without wasting syndrome. Cytokine levels were unaffected by either new or used PAN or CU dialyzers. PMID- 1751203 TI - Interleukin-1 kinetics in hemodialysis. AB - Interleukin-1 (IL-1) was measured in the plasma and in mononuclear cell (MC) lysates from patients on maintenance hemodialysis (HD) using either cuprophan (CU) or polysulfone (PS) membranes. Basal plasma levels of IL-1 in HD patients were significantly higher than those of uremic patients on conservative treatment or of healthy subjects. In 10 patients on conservative treatment, plasma levels of IL-1 increased significantly after 3 and 6 months of HD. During a single HD session, plasma IL-1 fell to 21% (CU) and 22% (PS) of pre-HD levels. Hemodialysis patients had a significantly higher intracellular IL-1 content than normal controls. During HD, a further increase was seen regardless of the membrane employed. A parallel in vitro study showed that IL-1 produced during HD requires at least 24 hours to be released, and that both CU and PS are able to bind and clear IL-1. PMID- 1751204 TI - A simple and practical method for assessing the adequacy of hemodialysis. AB - The authors plotted the values of the postdialysis/predialysis blood urea nitrogen ratio, R, of 104 functionally anephric maintenance hemodialysis patients against the Kt/V values that had been derived from a single-pool, variable volume, urea kinetic modeling method. When the R value was less than or equal to 0.4, the Kt/V value was consistently greater than or equal to 1.0. Maintaining an R value below 0.4 would ensure that Kt/V would never be less than 1.0. When a Kt/V value of greater than 1 is desired, an R value of less than 0.4 should be the goal. PMID- 1751205 TI - Response of continuous peritoneal dialysis patients to subcutaneous recombinant human erythropoietin differs from that of hemodialysis patients. AB - The hematologic response of 65 continuous ambulatory peritoneal dialysis (CAPD) patients to subcutaneous recombinant human erythropoietin (rHuEPO) was compared with that of 369 hemodialysis patients (HD). Pretherapy transfusions were more common in HD than CAPD. The response was measured as the change in hematocrit after 70 or more days of therapy (or as the hematocrit change normalized by a weekly dose) in CAPD patients. The weekly rHuEPO dose did not differ, but the dosing frequency was less in CAPD than in HD patients. Hematologic response parameters were greater in CAPD. Multivariate analysis showed that the response in both groups varied inversely with the frequency of dosing and with pretherapy baseline hematocrit. In HD subjects, the response also varied inversely with previous transfusion history. The authors concluded that CAPD patients responded better to rHuEPO than HD patients. This may be a result, in part, of lower ongoing blood losses. Patients with more severe anemias responded less well, whereas more sensitive patients were dosed less frequently. PMID- 1751206 TI - Uremic myopathy and calcitriol therapy in CAPD patients. AB - During 7 months of calcitriol treatment in eight CAPD patients, significant increases in serum creatinine and daily excretion of this substance in dialysis fluid were observed, but there was a significant decrease in creatinine in the urinary daily output. When therapy was stopped, creatinine levels fell to baseline in serum and peritoneal fluid, and urine values continued to decrease as previously observed. Dynamometric performance showed a significant increase during treatment, which remained after drug withdrawal. These findings suggest that the transient increase of serum creatinine during calcitriol treatment may be a result of an increased production and release of this metabolite from muscle. PMID- 1751207 TI - Tidal peritoneal dialysis. Urea and total nitrogen losses. AB - Tidal dialysis urea [NU] and total nitrogen [NT] clearances were obtained from nine patients, weighing 15-79 kg. Clearances normalized to a 70 kg body weight [nClr in ml/min/70 kg] increased with dialysate flow normalized to body weight [nFlow in ml/hr/kg]. The nClr [NU] = 6.862 + 0.352 x nFlow (r = 0.641, p less than or equal to 0.01). The nClr [NT] = 15.815 + 0.431 x nFlow (r = 0.460, p less than or equal to 0.01). Dialysate non-urea nitrogen [NT - NU] losses were 44.63 +/- 2.79 mg/kg daily, and these were altered minimally by the dialysate flow rate. PMID- 1751208 TI - Protein catabolic rate calculations in CAPD patients. AB - Four different approaches to calculating the protein catabolic rate (PCR, in g/kg/day) were investigated in 28 stable continuous ambulatory peritoneal dialysis (CAPD) patients and compared to the dietary protein intake (DPI) from a 3 day diet history. The modified Borah technique is based on the hemodialysis correlation, with the addition of measured effluent protein losses. The Randerson technique is a correlation similar to the Borah hemodialysis correlation, but it was established in a CAPD population. The Teehan technique estimates total nitrogen loss by adding the measured urea nitrogen loss to average values from the literature for protein, amino acid, and non-urea nitrogen losses. The Kjeldahl technique measures total nitrogen loss. All four techniques yielded similar PCR values (0.85-0.92 g/kg/day), none of which was significantly different from the DPI (0.89 g/kg/day). Based on the simplicity of the measurements and calculations, the Randerson technique is recommended for routine monitoring of PCR in CAPD patients. PMID- 1751209 TI - Plasma water filtration and lymphatic uptake during peritoneal dialysis. AB - To clarify further the extent, pathways, and significance of convective transport during peritoneal dialysis, acute transport studies were conducted in which five continuous ambulatory peritoneal dialysis (CAPD) patients underwent 6 hr dialyses (2 L infusate with 2.25% dextrose) on 2 successive days, with multiple sampling of both blood and peritoneal dialysate. Concentrations of permeants (urea, creatinine, uric acid, beta 2 microglobulin, and apolipoprotein A) and a radiolabeled marker (125I-polyvinyl pyrollidone [PVP]) were determined at 20-30 min intervals in dialysate and every 90 min in plasma. Intraperitoneal volumes and lymphatic flows were calculated from rates of dilution and disappearance of 125I-PVP. Intratreatment lymphatic flow rate averaged 76 +/- 15 ml/hr. Although lower than observed in small animal models and reported by some clinical groups, this level of lymphatic drainage was still sufficient to decrease net patient weight loss by approximately 50% and to resorb approximately 15% of metabolites in the peritoneal cavity, independent of molecular weight. Transcapillary ultrafiltration ranged from 7.4 +/- 1.5 ml/min at 10 min into the exchange to 1.3 +/- 1.5 ml/min at 345 min. Reverse ultrafiltration, from the peritoneal cavity back through capillary vasculature to the patient, was not observed in any patient in this study. PMID- 1751210 TI - Clinical application of low calcium peritoneal dialysate. AB - Low calcium dialysate (LCa) with calcium levels of 2.3 mEq/L was prepared for peritoneal dialysis, and its equilibration was compared with those of conventional dialysates with calcium contents of 3.5 mEq/L and 4.0 mEq/L. The variation in dialysate to plasma concentration ratios of total calcium of conventional dialysates was positive; that of LCa was negative. Mass transfer of calcium per day was positive and normal for calciums of 4.0 mEq/L (31 +/- 51 mg/day) and 3.5 mEq/L (-37 +/- 40 mg/day), compared with a negative balance for LCa (-157 +/- 26 mg/day). The LCa was used in six patients over 6 months. The doses of calcium carbonate and vitamin D also were increased from 1.2 +/- 1.5 to 5.4 +/- 3.3 g/day (p less than 0.05) and from 0.17 +/- 0.2 to 0.38 +/- 0.47 micrograms/day, respectively. Aluminum gel was discontinued. Low calcium dialysate may become the standard dialysate for stable continuous ambulatory peritoneal dialysis patients. PMID- 1751211 TI - Miniature membrane oxygenator for use in neonatal ECMO. AB - A new miniature membrane oxygenator (Kuraray KMO, size, 0.3 m2, with a priming volume of 47 ml, compliance of less than 0.1 ml/100 mmHg, and pressure loss of 45 mmHg) with improved gas transfer and mechanical durability was developed and tested. The membrane material is a hollow fiber double layer polyolefin. The testing procedures determined by the AAMI were followed, and the results showed improved O2 and CO2 transfer (70 ml/min and 55 ml/min, respectively). Hemolysis was within acceptable limits, and plasma leakage was undetectable after 7 days of perfusion. Clinical study demonstrated satisfactory performance. PMID- 1751212 TI - Hybrid respiratory support system with extracorporeal placental oxygenation. AB - The authors developed a novel hybrid system for long-term respiratory support with extracorporeal placental oxygenation. In this system, the patient's blood is oxygenated with O2 saturated artificial blood across the villous membrane during passage through the fetal circuit of the placenta, which is placed in a specially constructed artificial uterus. Human term placentas were obtained immediately after vaginal delivery and used for the experiments. The gas transfer performance of the current apparatus was 60 ml/min for O2 and 40 ml/min for CO2 at a blood flow rate of 1.0 L/min. From these results (and the assured blood compatibility of the placenta), the authors conclude that this system will become one of the most promising modalities for prolonged extracorporeal oxygenation. PMID- 1751213 TI - Use of an intravascular oxygenator/carbon dioxide removal device in an ovine smoke inhalation injury model. AB - The intravascular oxygenator/carbon dioxide removal device (IVOX) is a hollow fiber, implantable membrane oxygenator that lies in the vena cavae and is designed to augment gas exchange during acute respiratory failure. An ovine model of smoke inhalation injury (lethal dose for 50% of animals at 48 hr) was used in eight ewes to test the safety and efficacy of this device. The IVOX was placed in the vena cavae through a right internal jugular vein cut-down. A vacuum pump withdrew O2 through the hollow fiber membrane, and IVOX gas flow was measured with a flow meter. Outlet gas was analyzed for CO2 concentration. Changes in O2 exchange were calculated as changes in mixed venous O2 content with the IVOX on compared with the IVOX off, multiplied by the cardiac output. The IVOX did not significantly change cardiac output, mean arterial pressure, pulmonary artery pressure, or hemoglobin concentration measured every 6 hr for 48 hr. The maximum CO2 exchange averaged 40.2 +/- 10.5 ml CO2/min. The average change in oxygen exchange was 98.4 +/- 76.0 ml O2/min. Iliac vein injury from attempted IVOX placement without fluoroscopic guidance resulted in one death. The authors concluded that the IVOX was safe when properly inserted and provided approximately 25-30% of the gas exchange requirements in this model. PMID- 1751214 TI - Quantitative gas transfer into and out of circulating venous blood by means of an intravenacaval oxygenator. AB - The volume of O2 and CO2 transferred into/out circulating venous blood by various sized IVOX devices has been assessed by ex vivo and in vivo animal experiments and by reviewing the gas transfer data collected from the first 20 human ARDS patients studied during Phase I of the IVOX clinical trials. Data from these assessments indicate that oxygen transfer through the size 5 IVOX ranges from 15.4 to 18.0 cc/min; through the size 6 IVOX ranges from 22.8 to 35.5 cc/min; through the size 7 IVOX ranges from 28.5 to 66.7 cc/min; through the size 8 IVOX ranges from 34.9 to 66.3 cc/min; through the size 9 IVOX ranges from 45.9 to 115.7 cc/min; through the size 10 IVOX ranges from 52.9 to 133 cc/min. Quantitative carbon dioxide transfer through the various size IVOX devices closely follows the quantitative oxygen transfer achieved by IVOX. These quantitative data provide valuable information to clinicians considering using IVOX to augment the inadequate gas transfer existing in patients with acute, potentially reversible respiratory failure. They indicate IVOX transfers clinically significant quantities of O2 into and CO2 out of circulating venous blood in an intact subject without involving the subjects natural lungs. PMID- 1751215 TI - Prophylactic administration of tranexamic acid preserves platelet numbers during extracorporeal circulation in rabbits. AB - Neonatal extracorporeal life support is associated with platelet consumption and hemostatic disorders. This study in rabbits was undertaken to evaluate the effect of heparin coating and of the plasminogen and plasmin inhibitor, tranexamic acid on platelet consumption during extracorporeal circulation. Fibrinogen consumption was prevented by heparin coating, but platelet consumption was only prevented after the prophylactic administration of tranexamic acid. The authors concluded that inhibition of the fibrinolytic system had a specific effect on preserving platelet numbers, rather than improving the thromboresistance of the artificial surface. The main advantage of a heparin coating is the anticoagulant activity of the surface. Thus systemic heparinization can be reduced or omitted. PMID- 1751216 TI - Vascular access for extracorporeal circulation. Resistance in double lumen cannulas. AB - Double lumen catheters (DLCs) currently are being used for vascular access with extracorporeal circulation. Blood flow studies were done on various DLCs connected to a circuit made of polyvinyl chloride tubing. Sheep's blood was used with all catheters at flows of 200 and 400 ml/min. The inlet and outlet pressures were measured and resistances calculated. Modified versions of the Shiley and Kendall catheters, also were tested. In both catheters, resistance was reduced with the use of perfusion adaptors. Flow through catheters, with a diameter that exceeded the Luer fitting dimension, was compromised. The modified Shiley and unmodified Kendall catheters had the lowest resistance to flow, and they thus are best suited for extracorporeal circulation. PMID- 1751217 TI - Practical assessment of natural heart function using echocardiography in mechanically assisted patients. AB - Left ventricular assist systems (LVAS) can maintain the systemic circulation of patients with acute, profound heart failure. The assessment of natural heart (NH) function, however, is difficult in the clinical setting. The authors introduced a new index, heart rate-corrected ejection time/left atrial pressure (ETc/LAP) using echocardiography to evaluate NH function in 15 adult patients on the original LVAS for greater than 2 days. Bypass flow (BF) was gradually decreased according to the recovery of NH. Five patients were weaned from LVAS within 15 days, and LV function was well maintained (Group 1). Another six patients were weaned from LVAS within 21 days but died within 2 weeks (Group 2). The other four patients died on LVAS without recovery of NH (Group 3). In Group 1 patients, ejection time/pre-ejection period (ET/PEP) with LVAS assist increased continuously. In Groups 2 and 3, ET/PEP increased slowly and reached a plateau at approximately 10 days or remained low. Group 1 patients reached an ETc/LAP of 35 +/- 10 on LVAS within 7 days. Group 2 and Group 3 patient values were 18 +/- 2 (p less than 0.05) and 9 +/- 6 (p less than 0.01), respectively, on the seventh day. Based on these data, this new index provides an estimate of global NH function and a prediction of the probability of NH recovery. PMID- 1751218 TI - Quality of life in long-term survivors of the Hemopump left ventricular assist device. AB - The courses of 10 patients (nine men and one woman; mean age, 54 years) were reviewed to determine the long-term results of treatment with the Hemopump (Nimbus Medical, Inc., Rancho Cordova, CA) left ventricular assist device. Indications for treatment were postcardiotomy cardiogenic shock (n = 8) and acute cardiac allograft rejection (n = 2). Two of the patients with postcardiotomy shock required a bridge to transplantation. At follow-up (mean, 21 months), eight patients were alive: four were in New York Heart Association Functional Class I and four were in Class II. None had long-term adverse effects that were attributable to the site of insertion (e.g., limb ischemia or infected groin wounds). All the patients considered themselves independent in their daily activities, and most of the patients were able to exercise and pursue hobbies. The Hemopump appears to offer long-term survival with an acceptable quality of life to a population of patients whose survival would have been highly unlikely otherwise. PMID- 1751219 TI - Clinical evaluation of the Novacor totally implantable ventricular assist system. Current status. AB - The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval. PMID- 1751220 TI - Extended support with a left ventricular assist device as a bridge to heart transplantation. AB - The Heartmate-1000IP, an intracorporeal, pneumatically activated, pulsatile left ventricular assist device (LVAD) with textured blood-contacting surfaces, is undergoing clinical evaluation as a bridge to heart transplantation (HTx). During a 3 year period (January 1988 to April 1991), the authors evaluated 12 patients who required extended LVAD support (greater than 30 days) while awaiting HTx. Duration of support ranged from 31 to 233 days (mean, 117 days). LVAD performance was excellent, with average pump flow indices of 2.5-3.5 L/min/m2. Long-term antithrombotic therapy consisted of dipyridamole and aspirin in all except one patient who received only low-molecular-weight dextran. After the initial recovery period, prothrombin and partial thromboplastin times returned to baseline levels. Plasma-free hemoglobin levels averaged less than 10 mg/dl. One patient is currently receiving support (91+ days); the 11 other patients underwent successful HTx, with follow-up ranging from 7 to 36 months. The authors' cumulative experience with this LVAD totals more than 1,506 days of support (greater than 4 years) without evidence of any thromboembolic episodes. These results suggest that this LVAD provides an effective bridge to HTx for extended periods. PMID- 1751221 TI - Importance of ventricular arrhythmias in bridge patients with ventricular assist devices. AB - To evaluate whether bridge to transplant patients with ventricular arrhythmias (VA; fibrillation or tachycardia) are at risk of death before or during ventricular assist device (VAD) support, the records of 28 patients who were supported with VADs for periods of 0.1 to 370 days (mean, 35.3 days) were retrospectively reviewed. VADs were effective in reducing the incidence of VA by 36%; however, patients with ischemic heart disease had a high incidence of VA (44%) during VAD. Only one patient with non-ischemic heart disease (8%) had VA during VAD. All five patients supported with left ventricular assist devices who had VA during support survived. Overall, the occurrence of VA during VAD was not a mortality risk. Since VAs are not predictors of survival, the presence of VA should not influence patient selection. While biventricular assist devices may be necessary in patients with the most severe VA, an LVAD provides excellent support in many patients. PMID- 1751222 TI - Continuous monitoring of artificial heart pump performance. AB - Continuous monitoring of pump performance is essential and effective for optimal driving of a pulsatile blood pump. The authors contrived a practical method for continuous estimation of blood volume in a pump by measurement of electrical impedance (Z). This method was evaluated with the air-driven, diaphragm type pump. The pump was made from polyurethane and had two metal connectors at the inlet and the outlet ports. Z was measured by charging the alternating current (50 kHz, 0.4 mA) between two connectors as electrodes. In in vitro tests, Z reached maximum value during full-empty and minimum value at full-fill. The blood volume calculated by an empirical equation of Z was linearly related to the real blood volume (r = 0.99). In in vivo tests with goats, pump output estimated by this method was linearly related to pump output measured with an electromagnetic flowmeter and effectively evaluated pump performance. For calibration, this method needed only to measure Z at full-fill. This method was useful as a controller of a full-fill to full-empty drive. It was concluded that this method is a practical estimate of pump performance, even if implantable diaphragm type pumps are used, and easily applicable to any kind of pulsatile pump. PMID- 1751223 TI - Do humoral factors removed by plasmapheresis suppress the cellular immune system in cryoglobulinemia? AB - The efficacy of plasmapheresis (PP) is believed to be primarily related to the removal of plasma humoral factors. Little is known, however, about the effect of solute removal on cellular systems. The effect of the presence of cryoprecipitable proteins (CPPT) on mononuclear blastogenesis (MNB) and polymorphonuclear cell phagocytosis (PMN-P) was studied. MNB stimulated by concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) was significantly inhibited in cryoglobulinemic (CG) patients to 70, 75, and 60% that of normal controls, respectively. PMN-P were significantly suppressed to 30% that of normals. CPPT purified from cryoglobulinemic plasmas, type I and type III CG, exhibited higher suppressive effects (and in a concentration dependent manner) on normal MNB and PMN-P than albumin used as a control. The studies indicate that patients with CG have defective leukocyte function and that CPPT have suppressive effects on normal leukocyte function in vitro. Removal of plasma CPPT may improve the immunologic status of CG patients. PMID- 1751224 TI - Prolongation of cardiac xenograft function after reduction of natural antibodies using double filtration plasmapheresis. AB - A double filtration plasmapheresis (DFPP) technique was applied to selectively remove the natural antibodies in discordant xenotransplantation. A swine heart was heterotopically transplanted in a canine neck after two DFPP procedures during which 200 to 500 ml of plasma were replaced with the same amount of Hartman's solution containing 7% human albumin. Mean removal rate of IgC and IgM by DFPP ranged from 74.2 +/- 0.5 to 95.9 +/- 2.8%. The anti-swine lymphocytotoxic reaction of canine serum was decreased after DFPP but still remained in low titers. Mean graft survival time in the group treated by DFPP in which 1000 ml of plasma was totally replaced was prolonged to 107 +/- 47 min, while it was 9 +/- 5 min in the group without any treatment (p less than 0.01). Deposits of canine IgM and C3 on the vascular endothelium of the graft were observed on immunofluorescence, while there were no deposits of IgG. In conclusion, DFPP effectively removed the natural antibodies, resulting in prolongation of xenograft survival time. Immunofluorescence study suggested that natural IgM antibodies played an important role in this xeno-hyperacute rejection. PMID- 1751225 TI - Combined LDL apheresis and hemodialysis in a patient with end-stage renal disease and accelerated coronary atherosclerosis. AB - The first long-term experience with lipid apheresis in a hemodialysis patient with refractory combined hyperlipidemia and coronary heart disease is described. Simultaneous treatment was performed once a week using two separate machines connected by parallel flow. Correction of hyperlipidemia was achieved, accompanied by inhibition of progressive coronary heart disease, enabling kidney transplantation. PMID- 1751226 TI - Development of a 3-D artificial extracellular matrix. Design concept and artificial vascular media. AB - A photodimerizable monomer was synthesized and subsequently co-polymerized with a hydrophilic monomer to obtain a photocrosslinkable, water soluble polymer. This polymer attained a highly hydrated, gel-like phase on irradiation with ultraviolet (UV) light. Furthermore, incorporation of the well known cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) peptidyl moiety into the above co-polymer resulted, on UV light irradiation, in a three-dimensional hydrophilic gel matrix containing cell adhesive ligands. The UV irradiation on a mixture of photocrosslinkable and cell adhesive polymer and smooth muscle cells in a medium trapped the cells throughout the gel matrix, indicating that the cell-entrapped gel and the designed synthetic polymer biomimic the media of the vascular wall and extracellular matrix, respectively. PMID- 1751227 TI - Bioartificial thyroid. The in vitro culture of microencapsulated rabbit thyroid tissue. AB - A new technique of encapsulating thyroid tissue with an artificial membrane for protection against immune attack is reported. The membrane was made of calcium alginate and a poly-L-lysin coating. The membrane prevents the diffusion of large molecules such as hemoglobin but freely permits the passage of smaller molecules such as T4 and culture medium 1640. Because larger molecules are barred, the contents of the microcapsules are safe from immune system rejection. In vitro cultured, microencapsulated rabbit thyroid tissue secreted T3 and T4, achieving a concentration of 8.68 +/- 2.93 nmol/L and 245.23 +/- 124.87 nmol/L, after 3 days; this level remained steady for 6 to 9 days of incubation. These microcapsules show promise as a treatment modality and as a possible solution to the problem of immuno-isolation. PMID- 1751228 TI - Control of cellular orientation in two-dimensional tissue formation. Surface topologic effect of collagen fibers on endothelialization. AB - The authors studied the effect of polymorphous states of collagen on in vitro cellular orientation of bovine aortic endothelial cells (ECs). Little orientation of adherent ECs was observed on a nonoriented collagen coated surface, irrespective of culture period. Only ECs that adhered to fiber bundles 10 microns in diameter exhibited cellular elongation or alignment. The collagen membrane with highly oriented fine fibers provided no cellular alignment for ECs in sparse culture. Resultant confluent monolayers, however, were characterized by cellular orientation, suggesting that surface microtopology of collagen induces cellular orientation on incubation. Control of cellular orientation would be an elementary requirement for cell seeding technology leading to hybrid artificial organs. PMID- 1751229 TI - Liposome-embedded-heme as a totally artificial oxygen carrier. AB - To produce a totally artificial oxygen carrying substance, a synthetic iron porphyrin (heme) complex that is analogous to the oxygen binding site (protoheme) of hemoglobin was embedded in the phospholipid bilayer of a liposome. The O2 carrying capacity of this liposome-embedded-heme (L/H) was examined by exchange transfusions in beagles. Six beagles were divided into two groups. In Group I, 15 ml/kg of blood was removed, and the same amount of L/H solution was injected intravenously. In Group II, 30 ml/kg of blood was withdrawn, and the same amount of the L/H solution was injected intravenously. The mean L/H concentration in the blood was 0.9 mM in Group I and 1.5 mM in Group II. The oxygen volume transported by 1 mM of the L/H at 1 L/min of cardiac output in Groups I and II were 15 and 17 ml/mM.L.min, respectively. The oxygen volume consumed from 1 mM of the L/H at 1 L/min of cardiac output in Groups I and II were 7.7 and 8.3 ml/mM.L.min, respectively. O2 volume transported by the L/H in Groups I and II were 8 and 15%, respectively. O2 volume consumed from the L/H in Groups I and II were 12 and 24%, respectively. Thus, this liposome-embedded-heme has the ability to combine with oxygen, to transport it to the tissue, and to release it in the tissue. The oxygen volumes transported by and consumed from the L/H were proportional to the L/H concentration in the blood. PMID- 1751230 TI - Placement of aortic valve bioprostheses in sheep via a left thoracotomy. Implantation of stentless porcine heterografts. AB - Juvenile sheep provide a good model for assessing the efficacy of antimineralization techniques because of their rapid calcification of bioprosthetic valves. Stentless bioprosthetic valves are under evaluation for possible improved durability as aortic valve replacements. A left thoracotomy approach for aortic valve implantation, which facilitates intraoperative and postoperative hemodynamic data collection, has been developed and refined in 13 sheep. A critical feature of this technique is a partial rib resection that creates a soft tissue acoustic window to improve postoperative transthoracic echocardiographic examination. This allows both quantification of valvular gradients and qualitative assessment of valve leaflet motion and calcification. Excellent correlation was observed between the intraoperative invasive valvular gradients and the postoperative echocardiographic gradients available in four animals (mean gradient r = 0.96, p = 0.003; peak gradient r = 0.98, p = 0.0004). This is an excellent technique for serial postoperative noninvasive evaluation of valve prostheses implanted in the aortic position. PMID- 1751231 TI - Nondestructive analysis of mitral valve collagen fiber orientation. AB - Collagen is the most abundant and highest modulus component in mitral valve (MV) tissue. MV leaflet and chordal collagen ultrastructure were analyzed by small angle light scattering (SALS) and polarized light microscopy (PLM) to provide collagen fiber architecture mapping. It was hypothesized that structural arrangement strongly influences MV tissue mechanical properties and thus physiologic function. PMID- 1751232 TI - In vitro continuous wave Doppler gradients of mechanical valves in less than optimal orientations. AB - Continuous wave Doppler ultrasound is a noninvasive method of determining transvalvular gradients that may overestimate the gradients of prosthetic valves. It is theorized that a valve rotated or tilted in its annulus will create abnormally high velocities that calculate into derived gradients that are greater than those actually present. An in vitro apparatus was constructed to analyze the velocities and the actual and derived gradients of prosthetic valves in less than optimal orientations. Continuous flow studies of a 27 mm Omniscience prosthesis indicated good agreement between the actual and derived gradients with the valve's major orifice oriented toward the aorta's larger radius. These values increase as the valve is tilted to decrease its net opening angle. When the valve is rotated 180 degrees, the Doppler gradients tend to overestimate the actual pressure drops. These data indicate that certain valve misorientations create velocities that overestimate the transvalvular gradients. PMID- 1751233 TI - Advances in design principle and fluid dynamics of a flexible polymeric heart valve. AB - The three leaflet J-3 valve is manufactured in a medium open position with almost flat leaflets, whereby the stent is expanded by a cone shaped mold. After manufacturing, the dipcoated leaflets have stable closed and open positions. The transition succeeds with very low membrane stresses. Due to this design, the J-3 polymer valve showed superior hydrodynamic performance compared with commercial valves. In durability tests, prototypes have reached lifetimes up to 17 years. While animal tests are encouraging, they also reveal needed manufacturing improvements. PMID- 1751234 TI - In vitro quantification of regurgitant jet flow by color Doppler ultrasound and conservation of momentum. AB - Prosthetic valve regurgitant jets can be imaged with color Doppler ultrasound (CDU), but clinical quantitation remains elusive. An equation based on an integrated conservation of momentum analysis was implemented for CDU quantitation of regurgitation. This was compared with a simple, non-CDU momentum balance analysis recently reported that requires only a pulsed Doppler ultrasound (PDU) reading within the jet and a continuous wave Doppler (CWD) reading of the orifice velocity. For in vitro steady flows, the simple, non-CDU method was accurate only with PDU readings taken 5 cm from the orifice; flows were underestimated when readings 1 and 3 cm from the orifice were used. The CDU method was accurate, even when flows calculated from readings between 0.5 and 6.0 cm from the orifice were averaged together. PMID- 1751235 TI - Characterizing sleep disorders in chronic hemodialysis patients. AB - Forty-eight chronic hemodialysis (HD) patients (pts) completed questionnaires that used linear analogue scales (LAS), yes/no responses, and demographic data collection to characterize sleep disorders. Twenty-five pts (52%) reported problems sleeping. These pts graded sleep problems significantly higher than those without sleep problems (6.5 +/- 3 vs. 1.8 +/- 2, p less than 0.001 by LAS). Those with sleep disorders were more likely to smoke cigarettes (13/25 vs. 6/23, p less than 0.05) and have bone pain (14/25 vs. 6/23, p less than 0.05). No differences among pts with and without sleep problems were seen in age, gender, time on dialysis, caffeine intake, pruritus, feelings of sadness, worry, or anxiety, or Kt/V values (1.5 +/- 0.2 vs. 1.4 +/- 0.2, p less than 0.13). Restless legs (84%), onset insomnia (76%), and nighttime (76%) and early A.M. waking (72%) characterized the sleep disorders; symptoms suggesting nocturnal myoclonus were less common (20%). We conclude that sleep disorders are common in HD pts and may be exacerbated by tobacco use, bone pain, and restless legs. Kt/V does not correlate with sleep disorders. Further examination of this problem, including formal sleep studies, is needed. PMID- 1751236 TI - Mathematical modeling of erythropoietin therapy. AB - A simple mathematical model to describe hemoglobin (Hb) concentration response to recombinant human erythropoietin (EPO) therapy is proposed. The model is based on the assumption that Hb production increases linearly with EPO dose level. The resulting equation contains two patient parameters: 1) S, the proportionality constant between g Hb generated/L blood/wk and IU EPO administered/kg body weight/wk; and 2) tau, the patient erythrocyte lifetime in weeks. The model was applied retrospectively to 67 patients from the Canadian Erythropoietin Study, yielding an average error of 5.5 g/L between 27 measured and predicted Hb value pairs over the 27 week study. The model parameters, S (mean +/- SD = 0.015 +/- 0.005) and tau (14.0 +/- 4.1), varied over an order of magnitude. The model was also used to predict the EPO dose required to reach a target Hb of 110 g/L; the EPO requirements varied from 55 to 742 IU EPO/kg/wk (mean +/- SD = 225 +/- 124). It is recommended, based upon the model results, that EPO therapy be initiated at 3 IU EPO/kg/wk for each g/L difference between target and baseline Hb, with subsequent EPO dose adjustment guided by patient modeling. PMID- 1751237 TI - Red blood cell membrane permeability of uremic and normal cells. AB - Although there is extensive evidence that uremic red cells are more fragile and less deformable than normal cells, there are essentially no data on red cell membrane permeability in uremia. We have obtained data for creatinine and uric acid permeability of red cells from normal and uremic individuals (dialysis patients on EPO). The creatinine permeability of uremic cells was significantly less than that of normal cells (p less than 0.02), while the uric acid permeability was significantly greater than that of normal cells (p less than 0.01). Experiments with uremic and normal cells suspended in phosphate buffered saline, and with normal cells suspended in uremic plasma, indicated that uremia alters both the red cell membrane and the plasma, with an unknown plasma constituent affecting the permeability. PMID- 1751238 TI - Phosphate removal during hemodialysis, hemodiafiltration, and hemofiltration. A reappraisal. AB - Kinetics of phosphate removal, based on hourly collection of used dialysate or filtrate and hourly changes of phosphate plasma concentration, were studied in hemodialysis (QB 300; QD 500 ml/min), hemodiafiltration (QB 300; QD 500; QSF 25 ml/min), and hemofiltration (QB 250; QSF 70 ml/min) for six 5-hour sessions in each mode of therapy. Whatever the pretreatment phosphate concentration (1.5-2.0 mmol/L range), and whatever the treatment modality used, final plasma phosphate concentration was in the narrow range of 0.8-0.9 mmol/L, and about 50% of the total mass transfer occurred during the first 2 hours. At the third hour, a steady state is reached, suggesting that removal of phosphate is limited by the rate of phosphate transfer from body compartments to extracellular fluid, which was on the average about 362 mumol/kg.hr. Consequently, total phosphate mass transfer accounts only for 20 to 28 mmol per session. Control of pretreatment phosphatemia in the range of 1.5 to 2.0 mmol/L depends on daily phosphate binder prescription, calcitriol supplementation, and control of metabolic acidosis; one cannot rely on intermittent phosphate removal during the dialysis session. PMID- 1751239 TI - A multicenter study of short hour dialysis using AN69S. Preliminary results. AB - A multicenter prospective study of short hour (SH, less than or equal to 3 hr) dialysis using a high flux membrane (AN69S) plus volumetric control (VC), versus conventional (greater than or equal to 4 hr) (CNV) cellulosic non-VC dialysis, is ongoing. The study hypothesizes that SH treatment over 1 year will provide adequate dialysis, will not increase morbidity, and may improve quality of life. To date, 112 patients have been entered, and 54 have completed 6 months, 30 by SH. There were no differences in biophysiologic parameters at 6 months. Mean hospitalization was 5.24 days per patient. The SH group had a higher (p = 0.0374) hospitalization rate because of two patients. Quality of life was similar in SH and CNV groups. The study indicates that SH dialysis is feasible, safe, and as comfortable as CNV. PMID- 1751240 TI - Experimental study on limitations of anastomotic endothelialization of vascular prostheses. AB - We studied the effect of endothelial cell (EC) senescence on proliferation, migration, and endothelialization in vitro using a culture model. Two generations of cultured bovine aortic ECs were used. The results showed that 1) the senescent ECs had much reduced rates of proliferation, migration, and endothelialization in vitro, and 2) that the young ECs at the leading edge gradually developed morphology similar to that of the senescent ECs as endothelialization proceeded. Computerized videomicroscopic observation revealed that the ECs at the leading edge had higher motile activity than the ECs at the back. This suggests that the ECs at the leading edge, and circumvented from contact inhibition, may proliferate much more frequently than the ECs at the back. Localized cellular aging may result in decelerated or incomplete endothelialization, as found clinically. PMID- 1751241 TI - Dynamic internal compliance of a vascular prosthesis. AB - A new technique was used to measure dynamic internal compliance of a blood vessel or vascular graft subjected to dynamic internal pressure. The internal compliance can be broken into three categories: the volumetric compliance (CV), defined as (dV/V)/dP; the longitudinal compliance (CL), defined as (dL/L)/dP; and radial compliance (CR), defined as (dR/R)/dP. It can be shown mathematically that CV = 2 CR + CL. Thus, measuring any two of the three entities will also give the value for the third. A Dynatek DCT1 dynamic compliance tester was used for measuring the compliance of DenaflexTM biologic grafts and fresh bovine internal thoracic arteries, from which the Denaflex grafts were obtained by fixation. Volumetric compliance was obtained with the test sample mounted in a loose loop that allowed the sample to move both radially and longitudinally. By mounting the sample in a straight fashion that limited longitudinal movement, the radial compliance was determined. The longitudinal compliance was then calculated from the above relationship. Test results show that the fresh bovine artery had an average volumetric compliance of 26.1%/100 mmHg, radial compliance of 9.5%/100 mmHg, and longitudinal compliance of 7.2%/100 mmHg. The Denaflex vascular graft showed a reduction in longitudinal and radial compliance, compared to the fresh raw artery, as a result of extensive fixation. PMID- 1751242 TI - Facilitation of endothelial cell growth on hydroxylated ePTFE vascular grafts. AB - The authors have modified ePTFE by hydroxylating the surface using aluminum deposition and removal with sodium hydroxide. This process has no effect on the microfibrillar structure, but reduces the hydrophobicity of ePTFE. There were significantly greater numbers of rat aortic endothelial cells on the surface of modified as compared to control ePTFE after 14 days (469 +/- 44 vs. 4 +/- 3 cells/mm2, p less than 0.01, paired t-test). This simple chemical modification facilitates endothelialization, without using thrombogenic cell adhesives. PMID- 1751243 TI - Healing process of vascular prostheses seeded with venous tissue fragments. AB - Rapid neointima formation in fabric vascular prostheses seeded with autologous venous tissue fragments was examined. A piece of peripheral vein was minced into small fragments and stirred into 20 ml of saline. This tissue suspension was sieved through the wall of Dacron prostheses. The prostheses implanted in the descending aortae of dogs showed extremely rapid healing of the neointima. Endothelial cells lined the entire luminal surface within 14 days. There was no difference in the healing process between the area near anastomotic sites and the center. PMID- 1751244 TI - In vivo evaluation of porous versus skinned polyurethane-polydimethylsiloxane small diameter vascular grafts. AB - Two types of spongy polyurethane-polydimethylsiloxane (PU-PDMS) vascular grafts (1.5 mm ID, 450 microns wall thickness) were fabricated with either a skinned (SG) or a porous (PG) luminal surface and an open mesh filamentous external surface by a spraying, phase-inversion technique. Tubular membranes, 15-20 mm in length, were all implanted by the same surgeon as infrarenal aorta replacements in male Sprague-Dawley rats weighing 250-350 g (SG: n = 12, PG: n = 23). The patency rates at 2 weeks and 3 months were 0% (0/7) and 0% (0/1) for SG, 72% (8/11) and 8% (1/12) for PG. Because the wall structure of these grafts was relatively compact and did not provide enough communicating voids, another series of 15 highly porous luminal surface grafts was fabricated with a higher void to material ratio. These grafts (HPG) exhibited a 73% patency at 3 months, with a fully endothelialized surface. The authors conclude that a very open luminal surface structure, and a high wall porosity, are significant factors of graft patency in small diameter vascular prostheses made of a porous material. PMID- 1751246 TI - Effect of pulsatile reperfusion on myocardial high energy phosphates following global ischemia. AB - To evaluate the effects of pulsatile reperfusion (PR) on the postischemic myocardial phosphometabolites, 17 sheep were put on cardiopulmonary bypass (CPB) and randomly divided into a pulsatile group (P group) and nonpulsatile group (NP group). The heart was arrested by global ischemia for 45 minutes, then defibrillated and reperfused for 2 hours while the circulation was supported by CPB. Myocardial needle biopsies were obtained, and ATP, ADP, and AMP were measured with high performance liquid chromatography. There were no significant differences between the two groups in myocardial ADP and AMP. However, after 120 minutes of reperfusion, the myocardial ATP was restored in the P group, but continued to decrease further in the NP group. Experimental results imply that PR might reduce reperfusion injury and promote recovery of the ischemic myocardium. PMID- 1751245 TI - The development of a clinically relevant canine model of postperfusion syndrome. AB - Investigation into the complex etiology of the postperfusion syndrome (PPS) has been limited by access to only retrospective human case studies, and performance of animal studies that examine biochemical predictors of injury rather than the PPS itself. To determine whether a reproducible canine model of the clinical syndrome was possible, seven dogs underwent cardiopulmonary bypass (CPB) with a bubble oxygenator for 0 (n = 1, sham), 2 (n = 1), 4 (n = 1), and 6 (n = 4) hours. Arterial oxygenation, chest radiographs, serum creatinine, and total leukocyte and platelet counts continued to change through the second postoperative day, illustrating the need for prolonged follow-up (48 hours) to accurately detect postperfusion organ dysfunction. The dogs that did not undergo CPB for 6 hours (n = 3) did not develop important pulmonary dysfunction postoperatively, but three of the four dogs undergoing 6 hours of CPB developed profound, persistent, arterial hypoxemia associated with radiographic, histologic, and hemodynamic evidence of severe PPS. Early evidence of renal dysfunction was also apparent within 84 hours of 6 hour CPB. It is concluded that the canine long duration (6 hour) CPB model, with prolonged (48 hour) postoperative monitoring, generates a reproducible, clinically relevant model of human PPS. PMID- 1751247 TI - Membrane pore size and filtration selectivity in cryoglobulinemic plasma fractionation. AB - Efficiency of albumin (Alb) and immunoglobulin G (IgG) separation from cryoprecipitable proteins (CPP) and IgM was compared between a membrane plasma fractionator with a mean pore diameter (MPD) of 0.1 micron, surface area of 0.65 m2, and a new large pore diameter filter with a MPD of 4.3 microns, and surface area of 0.14 m2. In five in vitro tests at 4 degrees C using polyclonal cryoglobulinemic (CG) plasma from a patient treated by plasma exchange (PE), the large pore filter retained only 22% of the mass of Alb, and a comparable amount of CPP and IgM, as compared to the plasma fractionator, at a fraction of its total retention capacity. The new filter can replace PE in treatment of polyclonal CG. PMID- 1751248 TI - LDL cholesterol apheresis by dextran sulfate cellulose adsorption. Long-term experience in patients with familial hypercholesterolemia. AB - Five patients with diet and drug resistant familial hypercholesterolemia (FH) (low density lipoprotein [LDL] cholesterol, LDL greater than 230 mg/dl) were treated by LDL apheresis, using dextran sulfate cellulose adsorption (DSC), to prevent coronary heart disease (CHD). After membrane plasma separation, two 150 ml columns of DSC alternately adsorbed LDL, and were regenerated by 4.1% saline. Five patients received 230 treatments with 7 to 14 days intervals over 6 to 30 months. The treated plasma volume per session was 3.8 +/- 0.6 L. Post-apheresis values in percent of pre-apheresis were: total cholesterol, 42%; LDL, 27%; VLDL, 62%; HDL, 96%; triglycerides, 70%; WBC, 115%; platelets, 88%; C3 complement, 78%; fibrinogen, 67%; albumin, 94% (p less than or equal to 0.005 for all values). Safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to nonatherogenic levels of between 150 and 100 mg/dl, whereas high density lipoprotein remained unchanged. Adverse events (hypotension, angina pectoris, technical problems) occurred in six treatments. Long-term treatment of patients with therapy resistant FH by extracorporeal DSC adsorption is effective and safe. PMID- 1751249 TI - Simultaneous heparin extracorporeal LDL precipitation and hemodialysis. First clinical experience. AB - Simultaneous heparin extracorporeal LDL precipitation (HELP)-dialysis was carried out at weekly intervals in six patients with end-stage renal failure, associated hyperlipidemia, and a high risk of premature atherosclerosis. Evaluating 135 single treatments, a mean acute total cholesterol/LDL reduction of 31% and 39%, respectively, was found, while clearance of urinary substances was comparable to that in regular hemodialysis treatment. Treatment tolerance was excellent and no derangements in albumin, hemodialysis parameters, or blood coagulation were detected. PMID- 1751250 TI - Immunoadsorption of anti-A or anti-B antibody for successful kidney transplantation between ABO incompatible pairs and its limitation. Japanese Biosynsorb Research Group. AB - Kidney transplantation between ABO incompatible pairs, contraindicated because of a high incidence of hyperacute rejection episodes, has become feasible after provisional removal of anti-A or anti-B antibody from recipient canidates. Initially, a total of 54 patients were scheduled to be transplanted with ABO incompatible kidneys after removal of anti-A or anti-B antibody by immunoadsorption, using A or B antigen expressing trisaccharide immobilized on silica beads. Levels of anti-A and/or anti-B antibody (-ies) were negative (below less than X8 dilution) after three to four immunoadsorption treatments, and, thereafter, kidneys were successfully transplanted in 47 patients (incompatibility in A:21, B:25, AB:1). However, in four patients, anaphylactoid reaction occurred immediately after initiation of immunoadsorption, and double filtration plasmapheresis (DFPP) took place. Kidney transplantation was cancelled in three patients because of rebound to high level of anti-A or anti-B antibody, or appearance of T cell antibody after immunoadsorption. PMID- 1751251 TI - Safe and effective plasma exchange to remove antibodies prior to xenogeneic heart transplantation in small primates. AB - The ability of an on-line, rapid plasma exchange (PE) system to remove circulating antibodies in preparation for xenogeneic heart transplantation was studied. Plasma exchanges were performed 27 times on 13 rhesus monkeys weighing from 6.5 to 12.0 kg, using systemic heparinization, without untoward effects. Blood flow rates of 22-72 ml/min resulted in plasma collection rates of 7-22.5 ml/min. Serum immunoglobulin levels were decreased by more than 90%, and specific antiendothelial xenoreactive IgM was completely removed after two plasma exchanges. Transferrin levels were decreased 85-95%, and complement levels fell by greater than 80%. Platelets were partially conserved, with removal rates of 18 60%. All factors returned to normal ranges within 48 hours and no bleeding complications were encountered. When antiendothelial antibodies were removed in this manner, survival of a pig heart transplanted into a rhesus monkey was extended to 12 hours, from a baseline of 2 hours, without treatment. PMID- 1751252 TI - Development of an automatic control algorithm for the electrohydraulic total artificial heart without transducers. AB - To achieve a reliable and simple implantable total artificial heart, the number of implanted transducers providing the physiologic information required for automatic control should be minimized. To address this need, a new automatic control algorithm, based on a transducerless electrohydraulic total artificial heart (EHTAH) system, is proposed. The current EHTAH physiologic control algorithm relies on two implanted pressure transducers. Without these transducers, the information required for automatic control must be extracted from the running motor's parameters. These parameters correlated with the differential pressure across the axial flow pump used to actuate the EHTAH. Changes in this differential were chosen as a cue for cardiac output control. This algorithm can be viewed as depending upon systemic vascular resistance determined by subtracting mean right atrial pressure (RAP) from mean aortic pressure (AoP) and dividing the result by total cardiac output (CO). The difference between mean AoP and mean RAP was confirmed to correlate with the differential hydraulic pressure across the energy converter during the left systolic phase. As an interim configuration, a single differential pressure transducer measuring the differential hydraulic pressure across the energy converter was tested on a Donovan mock circulation system. The resultant CO response shows good sensitivity according to changes in both preload and afterload. PMID- 1751253 TI - Application of a new nuclear scintigraphy camera to evaluate flow and mechanical pumping of artificial hearts. AB - To assist in the development of an artificial blood pump, The Milwaukee Heart (MH 1), a new nuclear scintigraphy camera was used to study the wash-in and wash-out patterns of the MH-1. These studies indicate the MH-1 has an ejection fraction of 59.3%, with a stroke volume of 72 +/- 3 ml, and an afterload of 130 mmHg. Flow through the device is highly uniform, with no areas of stagnation. Regional ejection fraction images demonstrate homogeneous ejection from apex to base. The ability to scan through the first pass images allows study of wash-in, mixing, and wash-out of the tracer. In conclusion, this technique may provide a new approach to evaluating artificial heart pumps. PMID- 1751254 TI - Development of a totally implantable total artificial heart controller. AB - Using a one chip microcontroller, 87C196 (One chip EPROM), and an erasable and programmable logic device (EPLD), an implantable control system to drive a pendulum type electromechanical total artificial heart was developed. This control system consists of four parts: a main management system, a motor driver with power regulator, a state monitoring system, and a communication portion. The main system has a speed detector, proportional and integral (PI) control, pulse width modulation (PWM) generation, serial communication, and an analog data processor. Two kinds of power system are used, separated by eight photocoupler arrays to improve system stability. When the performance of each compartment was compared with that of the previously used Z80 microprocessor based control system, good correspondence was shown. Logic power consumption was reduced to one third that of the previous controller. Using mock circulation tests, the overall performance of the control system was evaluated. PMID- 1751255 TI - Comparison of microsphere and intraoperative quantitation of bronchial blood flow. AB - Although significant variation in bronchial blood flow (BBF) has been reported, precise quantitation is difficult because of the small sized vessels and variable anatomy. Ventricular balance is critical to the function of the total artificial heart (TAH), and variation in BBF can alter this balance in the bovine model. Bronchial blood flow was measured in 12 calves by two methods: six by the radioactive labeled microsphere technique (MBBF), and six intraoperatively (IBBF) during cardiopulmonary bypass (CPB). In the MBBF group, BBF ranged from 1.9 ml/kg to 16.0 ml/kg, whereas IBBF varied from 2.6 ml/kg to 10 ml/kg (NS). Cardiac output (CO) was significantly higher (p less than 0.0005) in the MBBF group. Bronchial blood flow in both groups was highly variable. The higher flow in the MBBF group may be attributed to the arteriovenous shunting of microspheres, whereas lower flow in the IBBF group may be secondary to physiologic changes during CPB. This technique, described to measure IBBF, can estimate large variations in the natural right to left shunt that contributes to imbalance in the TAH. PMID- 1751256 TI - Using magnostrictive metal as a pump for biomedical application. AB - A new theory of pumping fluids, including blood, has been developed using magnetostrictive technology. This new pump uses the magnetostrictive material known as Terfenol-DTM. A magnetic field is imposed on the Terfenol in periodic pulses causing it to expand and then relax to its original state. The expansion and relaxation of the terfenol cause a smooth, continuous flow of fluid. This pump is currently being built and will be tested as a left ventricular assist device, totally implantable artificial heart, or both. PMID- 1751257 TI - The valvo-pump. An axial, nonpulsatile blood pump. AB - The valvo-pump, an axial, nonpulsatile blood pump implanted at the heart valve position while preserving diseased heart muscle, has several advantages over an artificial heart replacement, including 1) a good anatomic fit to the natural heart, 2) less blood contacting surface, and 3) ease of implantation. The housing for the pump is a tube, 37 mm in diameter (maximum) and 33 mm in length. Within the housing there is an impeller with either 10 vanes (33 mm in diameter) or 5 vanes (22 mm in diameter). The impeller is connected to a samarium-cobalt-rare earth magnet direct current (DC) brushless motor measuring 23.8 mm in diameter and 30.2 mm in length. Sealing is achieved by means of a magnetic fluid seal. A guiding wheel with 4 vanes is located behind the impeller. The pump was studied on a hydraulic mock circulatory system to evaluate its performance characteristics. A pump flow of 6.9 L/min was obtained at a pump differential pressure of 48 mmHg, and flow of 3.1 L/min was obtained at 58 mmHg. The valvo pump can be made feasible by developing a small, high-output, power motor and an endurable seal, as well as by optimizing the impeller design. PMID- 1751258 TI - Ischemic heart disease, serum cholesterol, and apolipoproteins in CAPD. AB - Thirty-one patients, mean age 54 years, had been on chronic ambulatory peritoneal dialysis (CAPD) for an average of 38 months. Mean values (mg/dl) for triglycerides (567), total-C (267), LDL-C (133), and Apo-B (154) were elevated, and HDL-C (30) were low. The low values for total-C/Apo-B and LDL-C/Apo-B suggest an increase in the number of low density lipoprotein (LDL) particles, rather than in the amount of cholesterol per LDL particle. Without knowledge of lipids, ischemic heart disease for the 31 patients was categorized into five grades in the following manner. All patients were graded based on history (angina, myocardial infarction, and bypass surgery), electrocardiogram (EKG), and echocardiography. In addition, five patients underwent coronary angiography, the results of which were considered in their grading. The five grades were assigned as follows: Grade I, no evidence (n = 15); Grade II, angina with EKG ischemia (n = 4); Grade III, myocardial infarction (MI) (n = 1); Grade IV, MI with dyskinesia akinesia on echo (n = 4); Grade V, severe three vessel disease on angiography, or multiple infarcts, or Grade IV with heart failure (n = 7). Only Apo-B (r = 0.56) and total-C/HDL-C (r = 0.57) correlated with severity of grade, with p less than 0.001. When patients with and without detectable ischemic heart disease were compared by stepwise logistic regression, Apo-B was the only variable that independently predicted heart disease (p = 0.001). However, contribution of the lipid changes induced by CAPD has not been established. PMID- 1751259 TI - Decreased technique-related morbidity for continuous ambulatory peritoneal dialysis. AB - Patients who began continuous ambulatory peritoneal dialysis (CAPD) at the Mayo Clinic from 1979 to 1982 were hospitalized during that period 7.8 days per patient year (PPY) for access-related causes, whereas home hemodialysis (HHD) patients were hospitalized 1.6 days PPY. As the incidence of peritonitis decreased, it was found that patients who began CAPD and HHD from 1985 to 1988 were hospitalized during that period for access-related causes for similar amounts of time (1.8 vs. 1.2 days PPY, respectively). For CAPD patients, more than one half of the hospitalization time was for reasons other than peritonitis. PMID- 1751260 TI - Importance of ventricular arrhythmias in recovery patients with ventricular assist devices. AB - The effect of ventricular arrhythmias (VA) on survival was retrospectively reviewed in 41 patients (33 men, 8 women) who were supported with Thoratec ventricular assist devices (VAD [Thoratec Medical Inc., Berkeley, CA]) (17 left, 9 right, and 15 biventricular). Ages ranged from 15 to 71 years (mean, 56 years), and duration of support was 0.1-17 days (mean, 4.7 days). There was no significant difference in age, gender, or type of support between survivors and nonsurvivors, and no correlation between the type of support and incidence of VA. Only two patients (both on left ventricular assist devices [LVAD]) died as a direct result of VA. There was no significant difference in the occurrence of VA before or during VAD support between survivors and nonsurvivors. These data show that evidence of VA is not a predictor of survival in patients in whom myocardial recovery is expected. PMID- 1751261 TI - Myocardial tolerance to ischemia after resuscitation. Direct mechanical ventricular actuation versus cardiopulmonary bypass. AB - This study assessed myocardial ischemia after resuscitation from cardiac arrest using direct mechanical ventricular actuation (DMVA) or cardiopulmonary bypass (CPB). Myocardial ischemic tolerance was better after DMVA resuscitation. Resuscitation using DMVA, when compared with CPB, may improve outcome when subsequent coronary artery bypass grafting (CABG) is required. PMID- 1751262 TI - Jaw stiffness--an ill understood condition. PMID- 1751263 TI - Airway obstruction associated with the use of the Guedel airway. AB - Soft tissue lateral neck radiography was used in 22 male patients older than 60 yr, to determine the cause of pharyngeal airway obstruction during anaesthesia, before and after insertion of a Guedel airway. In six of the patients, the airway was radiologically and clinically clear with the head in the neutral position. Nine patients showed obstruction of the airway by a "shelf" of tongue, but seven were cleared clinically by dorsiflexion at the atlanto-occipital joint, and the remaining two by the Esmarch-Heiberg manoeuvre. In four of the 22 patients, the Guedel airway was lodged in the vallecula in the neutral position. This was cleared clinically by dorsiflexion at the atlanto-occipital joint in all these patients. In three patients the Guedel airway was obstructed by the epiglottis, but this was cleared by dorsiflexion at the atlanto-occipital joint in two; in the third patient, the Guedel airway slipped into the vallecula after dorsiflexion at the atlanto-occipital joint and remained there despite the Esmarch-Heiberg manoeuvre. There was only one instance in 66 trials of a clinically obstructed airway without an apparent radiological cause. However, there were 10 instances in 66 trials of a clinically clear airway with an apparent radiological cause for obstruction. PMID- 1751264 TI - Changes in amplitude and latency of the P300 component of the auditory evoked potential with sedative and anaesthetic concentrations of nitrous oxide. AB - The P300 component of the auditory evoked response was recorded from six subjects whilst they listened via headphones to a series of clicks which were interrupted unpredictably by a tone burst. They were instructed to press a button as quickly as possible after hearing the tone whilst breathing first air and then a series of increasing concentrations of nitrous oxide. Both the amplitude and the latency of the P300 changed in a dose-dependent manner with nitrous oxide, as did minimum reaction time. At nitrous oxide concentrations which prevented recall of any events that occurred whilst breathing the gas, four subjects continued to respond to the tone by pressing the button. In three subjects, the P300 wave was still detectable with a nitrous oxide concentration at which the task was no longer performed. These results show that there is retention of the ability to perform a reaction time task when there is a complete loss of recall of the task. There may be some recognition of an auditory stimulus, as manifest by a P300 wave, albeit reduced greatly in amplitude, in the absence of a motor response to it. The P300, therefore, merits investigation as a tool for studying conscious awareness under anaesthesia. PMID- 1751265 TI - Effects of i.v. lignocaine on psychological performance and subjective state in healthy volunteers. AB - In order to assess the effects of different doses of lignocaine on performance, nine healthy volunteers aged 21-34 yr received i.v. infusions of saline, low and high dose lignocaine (mean plasma concentrations 0.92 and 1.78 micrograms ml-1, respectively) in a double-blind randomized order. The Digit-Symbol Substitution Test (DSST) and Visual Analogue Scales (VAS) were performed repeatedly and a battery of performance tests once. The median (lower, upper quartile) number of correct responses for the DSST during the infusion period was: placebo 69 (67, 77); low 74 (71, 80); high 66 (61, 75) (P less than 0.001, General Linear Models; all pairwise comparisons P less than 0.05). None of the measures in the full battery showed any significant changes. VAS showed that subjects felt more interested (P less than 0.05), drowsy (P less than 0.01), dizzy, tense, abnormal, drunk and muzzy (P less than 0.001) with lignocaine than with placebo. These results confirm that lignocaine can produce acute performance effects (both improvements and impairments). Subjects were clearly aware of the presence of lignocaine, suggesting that subjective reports may be a useful indicator of its CNS effects. PMID- 1751266 TI - Propofol and midazolam act synergistically in combination. AB - We have studied interactions between i.v. propofol and midazolam for induction of anaesthesia in 200 unpremedicated female patients undergoing elective gynaecological surgery. Using end-points of "hypnosis" (loss of response to verbal command) and "anaesthesia" (loss of response to a 5-s transcutaneous tetanic stimulus), we determined dose-response curves for propofol and midazolam alone and in combination. For hypnosis, synergistic interaction was found (P less than 0.01), the combination having 1.44 times the potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of propofol required to produce anaesthesia was reduced by 52% in the presence of midazolam (P less than 0.01). The reduction in arterial pressure at induction was the same for the combination as for the individual agents. The cause of the synergism was not clear, but may have been interaction at CNS GABAA receptors. PMID- 1751267 TI - Intra-arterial thiopentone is directly toxic to vascular endothelium. AB - Ear artery segments removed from urethane-anaesthetized rabbits were mounted, perfused with Krebs solution, and pressurized before constriction with extraluminal noradrenaline. Vessel diameter was measured using a diode array mounted above the artery. After the degree of dilatation in response to intraluminal acetylcholine and glyceryl trinitrate was measured, vessels were perfused for 120 s with solutions of either 2.5-10% thiopentone or isotonic sodium carbonate in saline of matched pH. Administration of thiopentone solutions in all concentrations resulted in destruction of endothelial cells. The dilatation of vessels to glyceryl trinitrate and their myogenic reactivity was unaltered. Isotonic solutions of sodium carbonate (pH 10.6) had no effect on either endothelial cell function or direct vasodilatation. These data show that administration of thiopentone removes arterial endothelial cells, while vascular smooth muscle function is essentially unaltered. PMID- 1751268 TI - Jugular bulb cannulation: description of a cannulation technique and validation of a new continuous monitor. AB - We have compared in vivo oxygen saturation recordings obtained from the Oximetrix 3 with in vitro measurements using the Instrumentation Laboratories 282 Co Oximeter. The small mean difference (0.85%) and close limits of agreement (-4% to 6%) are close enough for clinical purposes, provided in vivo calibration is performed after insertion of the fibreoptic catheter and repeated at least every 12 h. Continuous monitoring of jugular bulb oxygen saturation during intensive care of brain injured patients is now possible using fibreoptic technology. This technique may be of value in detecting global ischaemia, and as a predictor and monitor of cerebral perfusion pressure therapy. PMID- 1751269 TI - Ketamine for caudal analgesia in children: comparison with caudal bupivacaine. AB - Fifty children undergoing inguinal herniotomy were allocated randomly to three groups to receive a caudal injection of either 0.25% bupivacaine 1 ml kg-1 with or without ketamine 0.5 mg kg-1 or ketamine 0.5 mg kg-1 with normal saline 1 ml kg-1. There was no significant difference in quality of pain relief, postoperative behaviour or analgesic requirements between the ketamine group and the two other groups. The bupivacaine-ketamine mixture provided better analgesia than the bupivacaine solution alone. Side effects such as motor weakness or urinary retention were not observed in the ketamine group. PMID- 1751270 TI - Maternal temperature regulation during extradural analgesia for labour. AB - We have studied the effect of analgesia on maternal temperature (oral and tympanic membrane) progression in 53 women during normal spontaneous labour. Three groups were studied: two received extradural analgesia with a continuous infusion of 0.25% bupivacaine with or without the addition of fentanyl; the third group received only parenteral opioid analgesia. All patients were afebrile and without clinical evidence of infection at the beginning of the study. Both groups of patients receiving extradural analgesia had a consistent and significant increase in temperature after approximately 5 h of analgesia; no such trend was observed in the parenteral opioid group. Alterations in mechanisms of heat dissipation may explain these findings. PMID- 1751271 TI - Clearance of atracurium and laudanosine in the urine and by continuous venovenous haemofiltration. AB - We have measured the steady state urinary clearances of atracurium, given by constant infusion, and laudanosine in eight patients undergoing artificial ventilation; all had normal renal function (mean creatinine clearance 81 ml min 1). Mean (SD) urinary clearance of atracurium was 0.55 (0.5) ml kg-1 min-1; that of laudanosine was 0.33 (0.2) ml kg-1 min-1. Simultaneous plasma clearances were 7.1 (1.4) ml kg-1 min-1 and 3.8 (1.5) ml kg-1 min-1, respectively. Notional haemofiltration clearances of the two substances were measured also in seven critically ill patients with renal and respiratory failure undergoing continuous venovenous haemofiltration. Mean (SD) clearances of atracurium and laudanosine in the haemofiltrate fluid were 0.11 (0.06) ml kg-1 min-1 and 0.09 (0.02) ml kg-1 min-1, respectively whilst plasma clearances were atracurium 6.7 (1.8) ml kg-1 min-1 and laudanosine 4.5 (1.8) ml kg-1 min-1. There were no significant differences between the plasma clearances of the drugs in the two groups, despite the difference in severity of sickness. Urinary clearance rates of atracurium and laudanosine were approximately 8 and 9% of that in the plasma, but the haemofiltration clearance of both substances was only 2%. PMID- 1751272 TI - Alcohol after sedation with i.v. midazolam-fentanyl: effects on psychomotor functioning. AB - Patients who arrive home several hours after outpatient surgery may drink alcohol. The extent to which residual drugs used in outpatient surgery interact with alcohol is not known. The purpose of this study was to determine if two i.v. drugs commonly used together in outpatient surgery, midazolam and fentanyl, have residual effects which would interact with alcohol drunk 4 h after injection. Twelve healthy male volunteers participated in a double-blind, randomized, placebo-controlled and cross-over study. Subjects were studied four times successively with a period of 1 week between trials. On each day of testing, the subjects received randomly, by slow i.v. injection (30 s), either saline followed immediately by saline, or midazolam 0.1 mg kg-1 followed immediately by fentanyl 2 micrograms kg-1. Four hours after the injection, the subjects consumed a beverage which either did or did not contain alcohol 0.7 g kg-1. Before and 1, 3, 5 and 7 h after injection (and before and 1 and 3 h after consumption of beverage), psychomotor performance and mood were assessed. While both the combination midazolam-fentanyl and alcohol had independent effects on the dependent measures in this study, there was no interaction between midazolam fentanyl and alcohol (no potentiating of effects of alcohol by i.v. sedation). We conclude that the effects of benzodiazepines and opioids that are short-acting and used in outpatient surgery have probably dissipated by the time a patient arrives home, and that effects from alcohol ingested at home will probably not be affected by recent administration of these drugs. PMID- 1751273 TI - Clinical and haemodynamic effects of milrinone in the treatment of low cardiac output after cardiac surgery. AB - We have studied the haemodynamic effects of i.v. milrinone, a new phosphodiesterase inhibitor, in patients with low cardiac output after cardiac surgery. Thirty-five patients with a cardiac index (Cl) less than 2.5 litre min-1 m-2 and a pulmonary capillary wedge pressure (PCWP) greater than 8 mm Hg were given a loading dose of milrinone 50 micrograms kg-1 followed by an infusion at one of three rates: 0.375 micrograms kg-1 min-1, 0.5 micrograms kg-1 min-1 or 0.75 micrograms kg-1 min-1 for 12 h. After 1 h there were increases in Cl (35%) (P less than 0.001), heart rate (13%) (P less than 0.01) and stroke volume index (19%) (P less than 0.005). There were decreases in mean arterial pressure (12%) (P less than 0.01), systemic vascular resistance (35%) (P less than 0.001) and PCWP (24%) (P less than 0.05). Pulmonary vascular resistance was unchanged or reduced and left ventricular stroke work index was unchanged or increased. The haemodynamic improvements were sustained throughout the infusion period. Milrinone was tolerated well: three patients developed tachycardia greater than 125 beat min-1, one patient developed atrial fibrillation and one patient had a short run of atrial bigemini. We conclude that milrinone is a useful agent in the treatment of patients with a reduced cardiac output after cardiac surgery. PMID- 1751274 TI - Renal function after cardiopulmonary bypass in children: comparison of dopamine with dobutamine. AB - We have compared low dose dopamine with dobutamine in conserving renal function in 142 children younger than 10 yr undergoing cardiopulmonary bypass (CPB). Patients were allocated randomly to receive a continuous infusion of either dopamine 2.5 micrograms kg-1 min-1 (group 1) or dobutamine 2.5 micrograms kg-1 min-1 (group 2) from the time of induction of anaesthesia. Administration of inotropes and diuretics was controlled strictly to agreed regimens. There was no clinical or statistically significant difference between the two groups in postoperative urine output, serum concentration of creatinine, fractional sodium excretion or need for diuretic therapy. This was true also of the subgroup of patients who received no other inotropic support. However, the subgroup of patients in group 1 who underwent periods of CPB in excess of 2 h (n = 17) had persistently greater postoperative serum concentrations of creatinine. Low dose dopamine did not appear to be superior to dobutamine for protection of renal function in these patients. PMID- 1751275 TI - Modification by drugs used in anaesthesia of CNS stimulation induced in mice by laudanosine and strychnine. AB - We have investigated in mice the effects of several drugs which may be administered as part of an anaesthetic technique on the convulsive threshold to laudanosine and to strychnine, which is reported to have a similar mechanism of action. I.v. administered propofol, thiopentone and midazolam increased the dose of convulsant necessary to produce seizure when administered 2 min before the convulsive stimulus. In contrast, methohexitone and etomidate exhibited a proconvulsant effect, although with the latter this was significant only in laudanosine-treated mice. Pethidine was proconvulsant in both laudanosine- and strychnine-treated mice, but morphine was proconvulsant only in strychnine treated mice. The effects of morphine, but not pethidine, were antagonized by naloxone 1 mg kg-1. Laudanosine, but not strychnine caused arousal from anaesthesia in subconvulsive doses. This and other evidence suggests that the mechanism of the CNS excitation produced by strychnine and laudanosine are not the same. PMID- 1751276 TI - Determination of contamination of a chemical warfare-proof operating theatre with volatile anaesthetic agents and assessment of anaesthetic gas scavenging systems. AB - Three types of anaesthetic waste scavenging systems (active antipollution system, Papworth Block passive system and activated charcoal absorber system) were compared with a non-scavenging control to assess their effectiveness in reducing waste halothane concentrations in a chemical warfare-proof operating theatre. All three systems were found to reduce the level of pollution significantly. PMID- 1751277 TI - Haemodynamic effects of propofol: induction with 2.5 mg kg-1. AB - Serial measurements of haemodynamic variables were performed at 1-min intervals in nine ASA I, unpremedicated patients before and for 5 min after induction of anaesthesia with propofol 2.5 mg kg-1. End-tidal carbon dioxide concentration was maintained within the normal range. Stroke volume and left ventricular function were measured by Doppler and cross-sectional echocardiography at the aortic valve. Systemic arterial pressure was measured by automated oscillotonometry and heart rate by electrocardiograph. Stroke volume, cardiac output, systemic vascular resistance, left ventricular stroke work and rate-pressure product were calculated. There was a decrease at all time points in systolic, mean and diastolic arterial pressure. There was an initial increase in heart rate and cardiac output, with a subsequent decrease to less than baseline. There was an initial decrease in systemic vascular resistance followed by partial recovery, and a delayed decrease in left ventricular function as measured by peak aortic blood flow velocity and acceleration. PMID- 1751278 TI - Inverse correlation between the peak venous serum concentration of bupivacaine and the weight of the patient during interscalene brachial plexus block. AB - Thirty-five adult patients with rheumatoid arthritis received for 36 interscalene brachial plexus blocks a standard dose of bupivacaine 200 mg, regardless of the weight (range 39.2-102.5 kg) of the patient. The peak venous serum concentrations (Cmax) of bupivacaine, measured by HPLC, were in the range 0.82-4.30 mg litre-1; there were no signs of toxicity. There was a very significant inverse correlation between the Cmax of bupivacaine and the weight of the patient (r = -0.5922; t = 4.285; P = 0.0001, Pearson's test). In spite of the correlation, only 35.1% of the total variance could be explained by regression. Thus weight had little influence on Cmax under interscalene brachial plexus block. PMID- 1751279 TI - Postoperative myocardial ischaemia: temporal association with nocturnal hypoxaemia. AB - Three patients presenting for elective aortic surgery were studied before operation and for up to 3 days after operation with ambulatory electrocardiographic monitoring and nocturnal pulse oximetry. Supplementary oxygen was administered for the first 2 days after operation and withdrawn on the 3rd morning after operation. Heart rate remained increased for the first 3 days after operation. Two patients developed episodes of myocardial ischaemia during the first 48 h after operation while their arterial oxygen saturation remained greater than 90%. On the third day, and during the third night after operation, both the severity and duration of myocardial ischaemia increased markedly, associated with arterial hypoxaemia. A temporal relationship between decreases in oxygen saturation and fluctuations in ST segment level were observed in the three patients. PMID- 1751280 TI - Unusual presentation of acute upper airway obstruction caused by an anterior mediastinal mass. AB - We report an unusual case of acute upper airway obstruction. Inhalation of a foreign body caused choking in a 5-yr-old child, but subsequent investigations revealed a large anterior mediastinal tumour, externally compressing the trachea and the main bronchi. Such a presentation may be deceptive and is important, as general anaesthesia may result in complete airway obstruction with fatal consequences. PMID- 1751281 TI - Transient ischaemic attack after spinal anaesthesia. AB - A case of transient ischaemic attack lasting 6 h occurred after spinal anaesthesia with bupivacaine. The level of sensory block was satisfactory and there was no significant hypotension. We discuss the possible cause of this previously undescribed complication. PMID- 1751282 TI - Temperature dependence of led and its theoretical effect on pulse oximetry. AB - Ambient temperature is known to affect the emission spectrum of a light-emitting diode (LED). This study has investigated the effect of changes in ambient temperature on the emission spectra of two LED with peak emission wavelengths similar to those used in pulse oximetry. There was a 5.5-nm increase in the peak wavelength for a 660-nm LED, and a 7.8-nm increase in the peak wavelength for a 950-nm LED as temperature increased from 0 to 50 degrees C. Using a simple theoretical model based on the Beer-Lambert law, the effect of these shifts in wavelength on pulse oximeter accuracy was examined and found to be negligible over the temperature range studied. PMID- 1751283 TI - Fresh gas requirement of the Bain system. PMID- 1751284 TI - Anaesthesia and bone marrow aplasia. PMID- 1751285 TI - Speed of onset of analgesia of diamorphine or morphine. PMID- 1751286 TI - Isoprenoid modification and plasma membrane association: critical factors for ras oncogenicity. AB - Association of ras protein with the plasma membrane is critical for its transforming activity. This association is promoted by a series of post translational modifications that are signaled by the consensus C-terminal CAAX motif present in all ras proteins. The recent discovery that a 15-carbon isoprenoid (farnesyl) group, derived from an essential intermediate in cholesterol biosynthesis, is attached covalently to ras proteins has stimulated considerable interest and has suggested several important new directions for ras studies. In particular, one promising pharmacologic approach for antagonizing oncogenic ras activity in human malignancies would be to design specific inhibitors of the enzymes that catalyze ras processing and thereby interfere with ras protein association with the plasma membrane. PMID- 1751287 TI - The DNA-activated protein kinase, DNA-PK: a potential coordinator of nuclear events. AB - DNA-PK is a moderately abundant serine/threonine protein kinase found in the nucleus of a wide range of eukaryotic cells. It is one of the few known cellular enzymes whose activity is regulated directly by DNA. Many DNA binding proteins, including a number of transcription factors, are substrates for DNA-PK in vitro. We suggest that this kinase may coordinate signal transduction pathways and nuclear events, including transcription, in response to changes in DNA or chromatin state. PMID- 1751288 TI - Maud Slye. PMID- 1751289 TI - Skeletal imaging in metastatic disease. AB - Radionuclide bone scanning is a well-established technique for the investigation of suspected metastatic disease to bone. Most commonly, primary cancers of breast, prostate, and lung tend to metastasize to the skeleton. Current topics on the role of bone scanning in patients with these conditions are reviewed. Despite the now known sensitivity of MR imaging for the detection of bone marrow involvement, bone scanning continues to be the methodology of choice in view of its simplicity, low cost, and ability to screen the whole body. Tumor markers such as prostate-specific antigens have a new role in the investigation of metastasis arising from prostate carcinoma; this area is also reviewed. Although bone-seeking radionuclide tracers have, on the whole, remained unchanged from a diagnostic point of view, new bone-seeking tracers have been developed for the treatment of unremitting pain in patients with multiple secondary tumors to the skeleton. This new area appears particularly promising and will widen the scope of the radionuclide tracer method as a therapeutic modality. Single-photon emission CT is helpful in improving the more exact localization of areas of increased tracer uptake in the skeleton and is therefore more often used as an imaging methodology. PMID- 1751290 TI - 201Tl myocardial perfusion imaging. AB - Despite predictions that 201Tl imaging would be completely supplanted by the new 99mTc perfusion agents, thallium perfusion imaging is alive and well. In fact, in the past year, important new information on thallium imaging continued to emerge. Among the new data, the reinjection of a "booster" dose of 201Tl after the redistribution images has been heralded as a breakthrough that would equal positron-emission tomography in the prediction of myocardial viability. Pharmacologic coronary vasodilation has been increasingly popular, especially since the approval of intravenous dipyridamole by the Food and Drug Administration and in view of recent studies showing that adenosine is a very attractive alternative to dipyridamole in patients who cannot exercise. Beyond the undisputed diagnostic value of dipyridamole-thallium imaging, data on risk stratification continue to accumulate for patients receiving peripheral vascular surgeries as well as for those recovering from a myocardial infarction. The advent of single-photon emission CT in combination with 201Tl imaging allows improved quantification of jeopardized myocardium. This technique has now been used increasingly to complement the information obtained from coronary angiography by the determination of the functional significance of known coronary stenoses. Recent studies have shown marked heterogeneity in the extent of jeopardized myocardium in patients with coronary artery disease. Equally important have been recent reports on the high prevalence of silent ischemia in patients undergoing 201Tl exercise scintigraphy. Technical progress has also enhanced the diagnostic capability of 201Tl imaging, allowing sharper identification of perfusion defects and quantification of reversible myocardial ischemia precipitated by exertion. Finally, one of the most exciting areas of research in thallium scintigraphy is its established prognostic value in patients with stable angina or those recovering from a myocardial infarction. Recently, these prognostic data have also been extended to patients with unstable angina or those receiving thrombolytic therapy. PMID- 1751291 TI - 99mTc myocardial perfusion imaging. AB - For more than 15 years, 201Tl has been used for measuring myocardial perfusion and viability although its physical characteristics, which include a photon energy of 68 to 80 keV and a physical half-life of 73 hours, are far from ideal. In early 1991, 99mTc tracers from the group of compounds known as isonitriles and boronic acid adducts of technetium dioximes (BATO) compounds were made available for general use in the United States, with approval by the Food and Drug Administration in late 1990. The uptake of these agents in the myocardium is proportional to regional blood flow. Because these tracers have 99mTc as the radiolabel, they have better physical characteristics--a gamma photon energy of 140 keV and a half-life of 6 hours--than 201Tl. The isonitrile with the best properties for myocardial imaging is 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) (Cardiolite, DuPont, Wilmington, DE). It has transient hepatic uptake and little or no myocardial redistribution, making it an ideal single-photon emission CT tracer. The commercially developed agent of the BATO group is 99mTc-teboroxime (Cardiotec, Squibb, Princeton, NJ). Its extraction fraction by the myocardium is higher than that of 201Tl and 99mTc-MIBI but its washout is very rapid and flow related. Because of the lack of redistribution with 99mTc-MIBI and the rapid washout with 99mTc-teboroxime, two separate injections are necessary for these new tracers to enable them to distinguish ischemia from scar tissue. It is recommended to perform the rest study first, and then to do the exercise study if a 1-day protocol is being used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751292 TI - Cardiac applications of positron-emission tomography. AB - Positron-emission tomography is an advanced imaging technology that can be used for the noninvasive evaluation of myocardial blood flow, determination of myocardial metabolism, and the assessment of myocardial tissue viability. 82Rb and 13N-ammonia represent the most commonly used tracers for qualitative evaluation of regional myocardial perfusion. In combination with pharmacologic vasodilation, these agents provide accurate detection of coronary artery disease. Comparative studies using single-photon emission CT with 201Tl have shown 82Rb positron-emission tomography to be superior in terms of diagnostic accuracy. The use of tracer kinetic modeling with the radiopharmaceuticals 15O-water or 13N ammonia has allowed accurate quantification of myocardial blood flow and determination of regional coronary flow reserve using dynamic positron-emission tomography imaging. The labeling of metabolic substrates such as 11C-palmitate, 11C-acetate, and 18F-fluorodeoxyglucose has proven to be useful in evaluating cardiac metabolism. The use of fluorodeoxyglucose uptake as a marker of exogenous myocardial glucose utilization allows the differentiation of ischemic but viable tissue from myocardial scar. The relationship of 11C-acetate turnover to oxidative metabolism and myocardial oxygen consumption may have important future applications for evaluating the efficiency of energy conversion of the heart into external work. Such a parameter could be used to evaluate the condition of patients with impaired left ventricular performance and to assess their response to therapy. Positron-emission tomography offers a useful research and clinical tool for the noninvasive evaluation of many aspects of cardiac disease. With the development of quantitative techniques, the clinical importance of positron emission tomography is expected to further increase in the future. PMID- 1751293 TI - Nuclear medicine detection of inflammation and infection. AB - The diagnosis and localization of inflammation and infection by nuclear medicine techniques continue to improve. The past year has seen a number of innovations and improvements in both commonly used radiopharmaceuticals and those still in the research phase. A good, in-depth knowledge of the many pathophysiologic changes that can occur at various sites and with different etiologies remains important in understanding and choosing which tests are most likely to provide useful clinical information. A number of important publications over the past year are reviewed. PMID- 1751294 TI - Hepatobiliary imaging. AB - Recent publications continue to refine the technique and interpretation of hepatobiliary scanning. Studies related to the evaluation of suspected acute cholecystitis have shown that morphine-augmented hepatobiliary imaging may not overcome the problem of false-positive study results in severely ill patients and the criterion for a normal study should be gallbladder visualization within 30 rather than 60 minutes. In patients with suspected acute cholecystitis, nonvisualized extrahepatic activity despite good hepatic uptake is highly predictive of acute cholecystitis, usually with biliary obstruction. The limitations of cholecystokinin-hepatobiliary imaging studies in patients with abdominal pain syndromes were defined and its use in evaluating common bile duct dynamics, and duodenogastric reflux was explored. Unusual findings and less common uses of hepatobiliary scanning were reported, including assessment of conjoined twins, liver transplantation, primary biliary cirrhosis, gallbladder perforation, and persistent splenic visualization. PMID- 1751295 TI - Pulmonary nuclear medicine. AB - The major nuclear medicine contribution to the pulmonary imaging literature for the past year was the inaugural report from the Prospective Investigation of Pulmonary Embolism Diagnosis study. Investigations focusing on the role of thrombolytic agents for the management of pulmonary thrombosis have advanced to the stage in which different therapeutic regimens are being tested along with new agents that continue to emerge. Ongoing research and clinical trials are evaluating newer radiolabeled aerosols in patients with airways and interstitial lung disease using imaging and clearance measurements. Positron-emission tomography continues to be utilized in a few research centers for tumor localization and characterization. PMID- 1751296 TI - Nuclear oncology. AB - Nuclear scintigraphy in the evaluation of patients with cancer is a significant part of the practice of clinical nuclear medicine. The oncologic applications in nuclear medicine are dynamic in that traditional techniques are undergoing change due to the development of new pharmaceutical agents and instrumentation. New scintigraphic applications in oncologic diagnosis, staging, and monitoring of therapy are emerging. The impact of these tests on the clinical management of cancer is significant. PMID- 1751297 TI - Neuronuclear medicine. AB - The importance of the development of the medical neurosciences is evidenced by the fact that the President of the United States and Congress have declared the 1990s the "decade of the brain." Special emphasis will be placed on managing and treating brain disease and, in particular, salvaging damaged brain from cerebral artery disease, trauma, tumor, and so forth. The advent of brain or cerebral care units in hospitals can be anticipated, analogous to the commonly available coronary care unit that resulted from recent concerted efforts to "conquer" heart disease. This effort will probably lead to a markedly expanded purview for clinical research in central nervous system disease. During the past year, a virtual explosion of publications in the mainstream medical literature on the basic and clinical utilization of nuclear medicine in the neurosciences has occurred. More than 400 substantive papers were published and the majority dealt with some aspect of positron-emission tomography. The more clinically pertinent of these papers are reviewed. PMID- 1751298 TI - Imaging of the skeleton and soft tissue in children. AB - Normal metaphyses in infants contain a step-off not to be confused with child abuse. Extension of physeal lucency into the metaphyses can be a sign of healing child-abuse fracture of experimental physeal fracture, as well as deferoxamine overdose. Sonography can reveal costochondral dislocation, the pattern of healing fracture callus, the patellar tendon in jumper's knee, synovium of rheumatoid arthritis, sequestrum in advanced osteomyelitis, the unossified dislocated patella, and, even after 2 years of age, the dislocated femoral head. Further developments concern bone scanning, MR imaging, CT, and plain films of specific trauma, tumor, and infectious, metabolic, and orthopaedic conditions. Ultrasound has been proven useful for radiologist removal of soft tissue foreign bodies, whereas CT can be helpful for osteoid osteoma nidus removal under imaging control. PMID- 1751299 TI - Imaging of the brain in children. AB - As proclaimed by the National Institutes of Health, the 1990s have been designated the "decade of the brain." Within this decade, we can expect to see an emergence of functional imaging in addition to the traditional role of anatomic neuroimaging to separate normal from pathologic anatomy. Technical advances continue to redefine the upper limits of resolution for both anatomic and functional imaging and provide us with a greater understanding of how disease processes affect normal brain growth and development. For example, whereas improvements in anatomic resolution will provide greater insight into understanding congenital malformations of the brain, through functional imaging, we will better understand the effect of disease on normal brain growth and development. PMID- 1751300 TI - Imaging modalities for the pediatric spine. AB - The role of MR imaging is emphasized in the evaluation of paraspinal and intraspinal soft tissue abnormalities. The technical aspects in performing a high resolution MR image of the pediatric spine in reference to imaging parameters, sedation protocol, and the use of intravenous gadolinium are detailed. The changes in the normal pediatric spine on MR imaging are demonstrated. The diagnosis and evaluation of specific intraspinal and paraspinal neoplastic disorders in infants and children are outlined in terms of their clinical presentation and MR characteristics. PMID- 1751301 TI - Pediatric chest imaging. AB - Several new therapies have resulted in marked improvement in morbidity and mortality rates for neonates with respiratory distress syndrome and related disorders. These therapies include the use of exogenous surfactant to treat existing surfactant deficiency in babies with respiratory distress syndrome. Follow-up of patients previously treated with extracorporeal membrane oxygenation for diaphragmatic hernia has shown continued pulmonary function abnormalities despite this therapy. Follow-up studies have also shown significant neurologic abnormalities. New uses of ultrasonography include scanning of the larynx and airway for evaluating retropharyngeal and parapharyngeal infections and evaluating perithyroidal inflammation secondary to congenital fistulas in this region. PMID- 1751302 TI - Imaging of the pediatric cardiovascular system. AB - Magnetic resonance imaging has become increasingly useful in the assessment of pediatric congenital heart disease. Spin-echo, gradient-echo, and cine techniques allow for both anatomic and functional cardiac assessment. MR imaging has proven most valuable in assessing complex heart disease and in visualizing areas that are sometimes poorly seen on echocardiographic studies. In particular, the anatomy of the aorta, central pulmonary arteries, and veins are usually well defined on MR imaging. Duplex and color Doppler sonography have become indispensable for evaluating the major vessels of the abdomen. The presence of clot, and quantity and quality of vascular flow as well as changes over time and response to therapy are readily assessed. Pulmonary sequestration is just one example of the burgeoning utility of duplex and color Doppler sonography in evaluating abdominal, mediastinal, and juxta-diaphragmatic masses. Sonography shows promise as a simple and accurate method for rapidly identifying the aberrant systemic blood supply in suspected cases of sequestered lung. PMID- 1751303 TI - Pediatric interventional radiology. AB - Hydrostatic reduction of intussusception has, until recently, been accomplished using barium sulfate or meglumine sodium diatrizoate, and has resulted in successful reduction in up to 80% of cases. Pneumatic reduction is an old technique but is new to North America. In a short time, air reduction has been widely accepted. It is easy to perform and success is achieved in over 80% of cases. The advantages of pneumatic reduction include a lower cost, shorter procedure time, and if perforation occurs, there is a lower likelihood of fecal contamination of the peritoneum. The vein of Galen malformation was initially described in 1895. The age at which symptoms occur and the severity of the clinical syndrome depend on the magnitude of arteriovenous shunting. Cross sectional imaging techniques are helpful for diagnosis and management planning. In infants with high-output congestive heart failure, neurointervention is now the treatment of choice. PMID- 1751304 TI - Pediatric genitourinary imaging. AB - The reviewed articles herein deal with morphologic as well as functional aspects of the pediatric genitourinary tract. Structural considerations, pathogenesis, and differential diagnostic criteria are the main focus in tumorous and nontumorous parenchymal and vascular diseases of the kidney and in malformations of the postrenal urinary and genital tracts including cloacal abnormalities. A number of case reports are included because they contain unusual yet important conditions and concepts of which the pediatric radiologist should be aware. Size, structure, and metabolic aspects of the adrenals and testes in congenital adrenal hyperplasia have been reported. Color Doppler ultrasonography in the context of acute scrotal disease was emphasized. Further diagnostic and therapeutic management of newborns and infants with prenatally diagnosed hydronephrosis underline the importance and consequence of fetal ultrasonography. Interventional procedures are somewhat limited in children, but the development of the biopsy gun that is now used in renal biopsies is a major improvement with regard to time, effectiveness, and safety of the procedure. Studies on measurement and variations conclude this review. PMID- 1751305 TI - Nuclear medicine. PMID- 1751306 TI - Pediatrics. PMID- 1751307 TI - The molecular genetics of systemic lupus erythematosus and Sjogren's syndrome. AB - With recent advances in understanding of the organization, complexity, and function of the major histocompatibility complex and other genes involved in the immune response, a rational approach to interpreting associations of systemic lupus erythematosus and Sjogren's syndrome with these genes is now possible. For example, both systemic lupus erythematosus and Sjogren's syndrome appear to be heterogeneous syndromes comprised of different major histocompatibility complex mediated (and perhaps T-cell receptor-and immunoglobulin genes-mediated) autoantibody responses. Moreover, HLA class II associations with systemic lupus erythematosus- and Sjogren's syndrome-linked autoantibody responses seem to be better explained by specific amino acid residues or epitopes on these class II heterodimers, residues or epitopes putatively involved in the binding and presentation of processed antigen to the T-cell receptor that can be shared by different class II alleles. These basic themes underlie this review of recent work in the immunogenetics of these autoimmune diseases. PMID- 1751308 TI - Autoantibodies and their idiotypes. AB - Idiotypes are serologically defined markers in the variable region of an antibody molecule. In the study of autoimmunity, these markers have been valuable probes in defining patterns of autoantibody variable region gene utilization, mechanisms of immune dysregulation, and the operation of the network in the generation of abnormal responses. Recent advances in the molecular analysis of immunoglobulin genes have provided insights into the structural basis of autoantibody idiotypes and the manner in which sequence homologies between idiotype-bearing antibodies and autoantigens can lead to autoreactivity. Immune manipulation using these sequences could lead to novel models of disease as well as prospects for immunotherapy. PMID- 1751309 TI - Murine models for systemic lupus erythematosus and Sjogren's syndrome. AB - Of the types of defects that have been observed in autoimmune mice, two are common to most strains and appear to be of critical importance in the development of autoimmune disease. The first of these is a deficiency in the maintenance of self-tolerance by B or T lymphocytes. This is an intrinsic defect due to genetic abnormalities that presumably affect an early developmental signaling mechanism. The disruption of early B- and T-cell development leads to the appearance of lymphocytes that are predisposed to loss of tolerance. In certain strains of autoimmune mice, it also leads to overproduction of Ly1+ (CD5+) B cells or CD4 CD8-B220+ T cells, which apparently do not contribute to autoimmunity. The second type of defect is a strain-specific, antigen-driven autoimmune disease syndrome. This defect is limited by the affinities of the available T-cell receptor and immunoglobulin variable regions and the efficiency of antigen presentation. Current evidence suggests that the major histocompatibility complex molecules play the most important role in determining which autoantigens lead to a pathogenic antigen-driven immune response. For example, the type and magnitude of the autoimmune response may be directed by the production of specific cytokines. The type of antigen and the context of its presentation can bias the production of cytokines that favor the production of the Th2 subset of CD4+ T helper cells. These cells secrete predominantly interleukin-4, interleukin-5, and interleukin 10, and may contribute to a chronic response and autoimmune disease. PMID- 1751310 TI - Clinical manifestations of disease activity, its measurement, and associated morbidity in systemic lupus erythematosus. AB - Although nephritis remains a very important clinical disease manifestation of systemic lupus erythematosus (SLE), the focus has shifted from issues of mortality to morbidity. An improved method for measuring renal function is presented, and the value of renal biopsy, specifically the chronicity index, is confirmed as a predictor of end-stage renal disease. Several studies detailing the generally favorable course in SLE patients with renal failure who have eventually required chronic dialysis or renal transplantation are discussed. A high frequency of cardiovascular manifestations, often subclinical, is documented, including abnormalities of ventricular and valvular function. The clinical course and response to treatment of SLE patients with diffuse interstitial lung disease and pulmonary hypertension are outlined. Cases of the unusual gastrointestinal presentation of protein-losing enteropathy in SLE have been described by several authors. The clinical correlates and significance of persistent rheumatoid-like arthritis and radiologic erosive and cystic bony lesions in SLE are discussed. Serologic markers of specific SLE disease manifestations and general predictors of disease activity are evaluated. Complications related to infection, malignancy, and pregnancy are described. PMID- 1751311 TI - Prognosis of systemic lupus erythematosus and the factors that affect it. AB - The prognosis of systemic lupus erythematosus has improved over the past four decades. Articles published in the past year continue to demonstrate this improved survival, both overall and in patients with renal disease. Several factors may be associated with improved survival, including earlier diagnosis, better treatment for systemic lupus erythematosus, and improved medical therapy in general. Hydroxychloroquine has now clearly been shown to prevent flares, and ancrod has been shown to improve renal disease in patients with glomerular thrombosis. Treatment with dialysis and transplantation resulted not only in improved survival but also in improved renal status, and reduction in overall disease activity. Specific organ damage continues to be an issue, primarily with regard to kidney disease and neurocognitive impairment. The inclusion of health status assessment in the evaluation of patients with lupus, and as an outcome measure, is discussed. PMID- 1751312 TI - Treatment of systemic lupus erythematosus. AB - Reports on a variety of therapies for systemic lupus erythematosus have been published over the past year. Most of these are single case reports or open studies. As reported last year in this journal, the potential uses of intravenous gamma globulin and plasmapheresis continue to be explored. The use of cyclophosphamide for nonrenal manifestations follows studies last year of its use for lupus nephritis. No major double-blind studies of therapy for lupus nephritis were published; however, the course of lupus patients receiving dialysis or grafts was the subject of three interesting studies. An interesting study on the ability of hydroxychloroquine to prevent disease exacerbations was also published. In summary, the reports of therapy over the past year represent variations on themes. The use of new agents will most likely be based on improvements in our understanding of the pathogenesis of systemic lupus erythematosus. PMID- 1751313 TI - Drug-related lupus. AB - All physicians should be alerted to the many drugs and other agents that are associated with drug-related lupus, as there is an increasing number of such drugs. A wide range of immune responses and antibodies are being reported with this syndrome. A new concern is the perceived ability of new biologic treatments to induce these autoimmune phenomena. More in-depth studies of various environmental factors are providing new insights into possible mechanisms. These include the immune responses to the drugs, their metabolites, and drug-altered conjugates; bioactivation mechanisms of drug protein conjugation; the role of macrophages in antigen recognition and processing; and lastly, the important role of the acetylation of various drugs and the relationship to immunogenetic factors. Continued study of this human experimental model of lupus will help to clarify the etiology and mechanisms of systemic lupus erythematosus itself. PMID- 1751314 TI - New developments in Sjogren's syndrome. AB - Over the past months, noteworthy contributions to our understanding of the clinical manifestations of Sjogren's syndrome have been made. Scintigraphic and echographic techniques have been refined to document xerostomia. Various systemic complications, such as nervous system involvement, pulmonary lesions, gastric and pancreatic dysfunction, and Raynaud's phenomenon have been further described. Mast cells have been shown to participate in the salivary gland infiltration, together with T lymphocytes, of which the majority are of the memory helper/inducer phenotype. Antinuclear antibodies are directed to SS-A/Ro and SS B/La particles. Two studies have been devoted to the cloning of the DNA encoding the 52-kD component of the former, and a series of SS-B/La DNA fragments have been generated to analyze the peptides of the latter. Virologic data have been provided, particularly the detection of anti-human immunodeficiency virus type 1 p24 protein in a number of Sjogren's syndrome patients, and the discovery of a human intracisternal A-type retroviral particle in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. PMID- 1751315 TI - Rheumatic fever, reactive arthritis, and musculoskeletal infections in children. AB - Infections may cause musculoskeletal symptoms either by inducing reactive disease or by directly infecting bone, joints, or muscle. Differentiation of reactive disease from direct infections of the musculoskeletal system is an important clinical problem. Both reactive disease and direct infections result from interactions of the host, the environment, and the infecting agent. This review provides an update of the recent literature on rheumatic fever, the classic example in rheumatology of reactive disease, and direct musculoskeletal infections. PMID- 1751316 TI - Genetic disorders of connective tissues. AB - Due to the growing knowledge of structure and function of extracellular matrix proteins, congenital abnormalities of connective tissues are identified or suspected in an increasing number of clinical disorders. In osteogenesis imperfecta and two subtypes of Ehlers-Danlos syndrome, the affected matrix proteins were identified and mutations in the corresponding genes (procollagen type I and type III, respectively) could be demonstrated. Some forms of chondrodysplasia were shown to be associated with mutations in the gene encoding for the cartilage-specific collagen (type II). In part, the clinical phenotype is determined by the tissue-specific distribution of these collagens. However, the correlation of location and character of the mutation to the phenotype is only just emerging and remains unpredictable in most cases. Recent findings suggest the mutations in matrix genes may be causative not only for rare pediatric diseases but also for more common disorders such as osteoarthritis or aortic aneurysms. PMID- 1751317 TI - Juvenile chronic arthritis and juvenile spondyloarthropathy. AB - Clinically recognized subgroups of juvenile chronic arthritis and the juvenile spondyloarthropathies are gradually being shown to be immunogenetically distinct; greater subdivision may ultimately be required. Mechanisms by which the association of certain genes work await further elucidation. Meanwhile, therapy such as intravenous gamma globulin may be most effective in systemic disease. Sulfasalazine is recommended for patients with later-onset pauciarticular disease, particularly HLA-B27 patients. Methotrexate should probably be reserved for severe unresponsive disease, particularly polyarthritis, until side effect profiles are better evaluated. PMID- 1751318 TI - Systemic lupus erythematosus, dermatomyositis, scleroderma, vasculopathies, and other connective tissue disorders in children. AB - The diverse disorders discussed in this review share the underlying features of multisystem involvement and vasculitis as a part of their pathophysiology. A review of morbidity seen in childhood-onset systemic lupus erythematosus reveals the need for careful monitoring for complications secondary to treatment and infections. Current understanding of the pathophysiology and risks of developing the neonatal lupus syndrome are reviewed, with the important recognition of the association of specific maternal autoantibodies with affected offspring. A review of current management issues in the treatment of juvenile dermatomyositis is discussed. Kawasaki disease, one of the most common childhood vasculitides, continues to provoke interest in the areas of accurate diagnosis, potential etiologic role of common viruses, management, and late morbidity. Interesting case reports of children with unusual features of the more rarely described disorders of Sjogren's syndrome, scleroderma, and Behcet's syndrome are discussed. PMID- 1751319 TI - Advances in pediatric orthopaedics. AB - New technology is fueling advances in pediatric orthopaedics. Ultrasonography represents a safe and highly accurate method of screening for hip dislocation and dysplasia that is superior to the clinical examination. Image intensification now provides a safe and more anatomically accurate method for the operative treatment of slipped capital femoral epiphysis. Magnetic resonance imaging allows for greater accuracy in the diagnosis of subtle neural abnormalities associated with congenital spinal deformities. Adjuvant chemotherapy and the treatment of osteogenic sarcoma have greatly improved the survival rate and permitted the use of limb-sparing procedures in children. PMID- 1751320 TI - Systemic lupus erythematosus and Sjogren's syndrome. PMID- 1751321 TI - Pediatric and heritable disorders. PMID- 1751322 TI - [The principles of radical surgery for colorectal cancer]. PMID- 1751323 TI - [The evolution of immunosuppression in clinical kidney transplantation: the experience of 700 cases]. AB - Kidney transplantation was first introduced in Italy in 1966 by the II Surgical Pathology of the University of Rome giving a great contribution to the development of the transplant surgery in this country. The authors report their 25-year experience analyzing the results obtained in more than 700 kidney allografts. A progressive refinement in the surgical transplant technique both from cadaver and live as well as clinical trials on new immunosuppressive protocols characterized their work. PMID- 1751324 TI - Photodynamic therapy in general surgery. AB - Authors' experience in detecting neoplasms by a computerized telethermographic system in animal models is reported. The new technique seems to have a great potential as a photo-diagnostic method particularly when followed by the surgical treatment or the photodynamic therapy (PDT) of the neoplastic lesions. Literature reports on the PDT of tumors are reviewed. PMID- 1751325 TI - [The surgical therapy of morbid obesity: our experience]. AB - The authors report their experience of two years in the surgical management of morbid obesity. The efficacy of the biliopancreatic diversion, method created by Nicola Scopinaro, is underlined. Sixteen patients affected by morbid obesity were treated with this method. Results obtained are comparable to those reported in literature; therefore the authors have been induced to continue in this direction. PMID- 1751326 TI - [Primary intrahepatic calculosis: hepatic lithotomy or hepatectomy?]. AB - The authors discuss about the different surgical approaches in the management of primary intrahepatic stones, conforming their experience to literature reports. In the future they hope for a more conservative treatment on the basis of the good results obtained with percutaneous transhepatic fiber cholangioscopy (P.T.C.S.) and ultrasonographic extra-body lithotripsy recently adopted in the clinical practice. PMID- 1751327 TI - [Postoperative esophageal-visceral fistulae: their prevention and treatment]. AB - A series of 12 cases of esophageal anastomotic leakage following esophageal surgery observed from 1969 to 1989 is retrospectively analyzed. In the period 1969-1975 6 patients were treated in emergency and the mortality rate was 66.6%, while the remaining 6 patients observed from 1975 to 1989 were treated conservatively with total parenteral nutrition (sometimes associating adequate surgical drainage): the mortality rate was 16.6%. In conclusion, not only in the treatment of anastomotic leakage, but also in its prevention, artificial nutrition has a crucial role. The outcome of thoracic and abdominal fistulas depends mainly on adequate drainage, not necessarily surgical. Cervical fistulas heal in 2-4 weeks, but strictures arise frequently and respond to endoscopic dilatation. PMID- 1751329 TI - [The use of a new prosthesis for ureterocutaneostomy]. PMID- 1751328 TI - [Infectious chemoprophylaxis in colorectal surgery. A multicenter study of imipenem-cilastatin vs. cefuroxime and metronidazole or cefotetan]. AB - The authors report the results of a multicentric clinical study on prevention of surgical infections in colorectal surgery by chemo-antibiotic prophylaxis. This trial was carried on to evaluate the effect of imipenem-cilastatin (1 g i.v. just before operation and 1 g i.v. 3 hours from surgical procedure) vs. cefuroxime + metronidazole (1.5 g + 0.25 g i.v.) or cefotetan (1 g i.v.) given with the same modalities. In 48 patients undergoing colorectal resection (47 with malignant neoplastic disease) 24 were treated with imipenem, 18 with cefuroxime and 6 with cefotetan. In group A (imipenem-cilastatin) the infection rate was 4.2% (1/24 cases), in group B (cefuroxime + metronidazole or cefotetan) postoperative infections were registered in 4 out of 24 cases (16.6%). This study documented the good results of systemic chemoprophylaxis and the great efficacy of imipenem cilastatin in colorectal surgery. PMID- 1751330 TI - [The use of human fibrin glue in fistulous pathology of the lung]. AB - Currently, bronchopleural fistulas present a decreasing complication rate in thoracic surgery, especially since surgical management of tubercular infections is no longer needed. The introduction of non-reacting suture materials and the technological advances have also lowered the incidence of such complication. Although fistulas tend to be chronic, their treatment is possible. Today, in fact, the use of human fibrin glue gives positive results which depend on the extent of the fistula as well as the adherence of the glue to the bronchial wall. The authors report their experience in two cases treated with human fibrin glue. PMID- 1751331 TI - [Observations in sclerosing cholangitis]. AB - Sclerosing cholangitis is a rare liver disease of unknown etiology with a slow but progressive course. The authors report their experience and illustrate some surgical procedures to preserve bile duct patency in view of a liver transplantation program. PMID- 1751332 TI - [A commendation of Prof. C. W. Lillehei on the occasion of the conferring of an honorary degree]. PMID- 1751333 TI - [Anatomicosurgical study of the superior mesenteric vein]. AB - Results of an autoptic study of the superior mesenteric vein in thirty cadavers are reported. The anatomo-surgical patterns of the venous axis are emphasized. In fact, a better knowledge of this vessel allows an easier and safer surgical approach during pancreatic resections. PMID- 1751334 TI - [Intensive therapy in general surgery]. AB - A good diagnostic protocol as well as a proper preparation to surgery and a careful intensive observation (associated if necessary with an intensive therapy) can lead to a better prognosis in major surgical procedures or routine surgery in poor risk patients. Candidates to ICU are divided in three classes: type A is a stable patient requiring constant monitoring for high probability of complications, type B is still a stable patient who needs an intensive nursing; finally type C is an instable patient who requires a true intensive care. In the surgical department of USL 20/B Figline Valdarno (FI) a postoperative Intensive Care Unit (ICU) has been established in the last three years: a three-bed section with its own staff is located in the surgical department itself. In 37 months 467 operated patients requiring intensive observation or intensive therapy have been admitted. PMID- 1751335 TI - [Nonepithelial nonlymphomatous tumors of the stomach]. PMID- 1751336 TI - [A subclavian vein lesion due to the positioning of a chest tube via thoracostomy]. AB - The authors describe an unusual complication of chest tube placement: subclavian vein lesion. After a literature review concerning complications of chest tube placement, the authors conclude that associated risks may be best minimized with a strict adherence to standardized technique and management protocol. PMID- 1751338 TI - [A case of ganglioneurofibroma of the lung]. AB - A case of ganglioneurofibroma of the lung surgically managed is reported. Symptoms were those of an enlarging mass in the thorax. The essential clinical features of the condition are briefly discussed. PMID- 1751337 TI - [Respiratory complications in compressive goiters]. AB - Authors' experience in respiratory complications of compressive goiter is reviewed. Three cases with typical symptoms, relative therapy and outcome are reported. Appearance of respiratory distress should urge to avoid delay in elective surgery performing. In case of acute respiratory failure, immediate emergency tracheostomy is mandatory, subsequently followed by elective intervention. In case of malignancy, if radical surgery is not possible, tracheostomy is the short and medium-term palliative surgical treatment of choice. PMID- 1751339 TI - [Acute appendicitis secondary to carcinoma of the right colon]. AB - In a series of 954 laparotomies performed for suspected acute appendicitis 5 (0.5%) cecal carcinomas were encountered. When considering patients over 50 years of age only, the incidence of right sided colon carcinomas raised to 5%. The authors review the therapeutic options in order to optimize patients' survival. PMID- 1751340 TI - [Morgagni-Larrey hernia: 2 clinical cases]. AB - The authors report two cases of hernia of Morgagni, respectively observed in a 42 year-old man and in a 16-year-old boy. In the first case the diagnosis was previous (20 yrs.) to surgical treatment. On the contrary, in the second case the diagnosis was not possible before surgery because of the patient's young age and mild symptoms. Surgical treatment, through thoracotomy in the first case and laparotomy in the second one, was able to repair the diaphragmatic gap. PMID- 1751341 TI - [Angiolymphoid hyperplasia with eosinophilia (Kimura's disease): an unusual pathology]. AB - The authors report a case of Kimura's disease recently observed. Diagnostic problems related to this rare pathologic condition as well as current and most reliable etiopathogenetic hypothesis are emphasized. Histopathological and clinical features are described in detail. PMID- 1751342 TI - [Ketoprofen in the prevention of postoperative pain in abdominal surgery. A multicenter study]. AB - Two-hundred-forty-eight patients undergoing abdominal surgery were admitted to a multicentric clinical trial. The patients were randomly assigned to a single i.v. dose of ketoprofen or acetylsalicylic acid, 15 minutes after the end of operation. Ketoprofen showed a better analgesic activity with a statistically significant difference at 2 and 4 hours after administration. Two patients treated with ketoprofen reported vomiting and skin rash respectively. The results of this study confirm the efficacy of ketoprofen for the prophylaxis of postoperative pain in abdominal surgery. PMID- 1751343 TI - [Esophagogastric devascularization in bleeding esophageal varices due to portal hypertension: median-term results]. AB - The authors report their personal experience in the treatment of bleeding gastroesophageal varices related to portal hypertension. The excellent results of the esophagogastric devascularization observed in the middle-term follow-up (5 years) reinforced authors' opinion on this surgical procedure as the most valid alternative to derivative surgery. Furthermore, they emphasize esophagogastric devascularization can often replace, on principle, derivative surgery. PMID- 1751344 TI - [Infections in surgery]. AB - In this paper the authors review current concepts on surgical infections. Topics covered are: hospital-acquired surgical infections, prognostic indexes, antibiotic prophylaxis, surveillance and control measures. PMID- 1751345 TI - A comprehensive approach to the analysis and interpretation of the resonances of spins 3/2 from living systems. AB - An extensive protocol for the study of tissue resonances of spin 3/2 nuclei is described. The roles of the most relevant multiple pulse experiments are indicated. Their theory is organized in terms of irreducible tensor operators and the pulse and quadrupolar relaxation transfer functions which relate them for a type c spectrum. A systematic approach to the interpretation of the temperature and/or magnetic field dependences of all six of the relaxation rate constants of the resonance of a single population of isolated spins in fast exchange, and giving rise to a type c spectrum, is presented. An experimental calibration and an application of this protocol are presented in an accompanying paper. The comprehensive method we describe has a number of practical benefits in the interpretation of the physiological spectra obtained from conventional one pulse experiments. A consideration of the appropriate transverse relaxation transfer function leads to an analytical expression for the heretofore empirical NMR visibility factor. This includes factors which account for relaxation during the receiver 'dead' time and relaxation during the pulse itself. Also, consideration of realistic transverse relaxation times likely to be observed in tissue leads to a reasonable strategy for the quantitative resolution and integration of in vivo spectra obtained in the presence of hyperfine shift reagents. PMID- 1751346 TI - The molecular environment of intracellular sodium: 23Na NMR relaxation. AB - The comprehensive approach described in the accompanying paper is illustrated here with the 23Na signal of a concentrated solution of bovine serum albumin (BSA) in saline and the intracellular (Nai) 23Na resonance of a dense suspension of Na(+)-loaded yeast cells. We use frequency shift reagents to discriminate the latter from the extracellular resonance. We find that the Nai signal corresponds to that of an effective single population of Na+ ions exhibiting a single type c spectrum. This is true despite the fact that the yeast protoplasm is too large and too compartmentalized for a given Na+ ion to sample its entirety on the relevant NMR timescale. Our results show clearly that, in addition to the decay of transverse magnetization, the recovery of longitudinal magnetization is biexponential. This is required for a type c spectrum but has not often been detected. The temperature dependence of the relaxation rate constants of the Nai resonance is not consistent with either a simple Debye process or a discrete exchange mechanism connecting two sites in the fast limit. We have fitted the data using an asymmetric continuous distribution of correlation times for the fluctuations of electric field gradients sensed by the Nai nuclei. The analogous distribution function for the Na+ in a 44% (w/w) BSA solution is quite similar to that of the Nai at the same temperature. This suggests that while the macromolecular environment of the Nai ions is quite congested, it is also isotropic on quite a small spatial scale. Also, one can use the correlation time distribution function, obtained from fitting the relaxation data, to calculate a relaxometry curve. This is useful because experimental 23Na relaxometry is difficult. The calculated curve may be a reasonable model for the mostly extracellular 23Na resonance encountered in vivo. PMID- 1751347 TI - Characterization of a microcarrier cell culture system for 23Na MR spectroscopy studies. AB - A MR spectroscopy method is described for the simultaneous discrimination and observation of sodium from the three compartments created by an intact cell monolayer. Results are reported for Madin Darby Canine Kidney (MDCK) cells, an epithelial-like continuous cell line, cultured on Cytodex 1 microcarrier beads and perfused with medium containing 6 mM dysprosium (III) tripolyphosphate [Dy(TPP)2(7-)] as shift reagent. The sodium spectrum shows three resonances which are assigned to the shifted intrabead (basolateral) and extrabead (apical) pools and the unshifted intracellular pool. Ouabain inhibition of the Na(+)-K(+)-ATPase cellular pump mechanism was used to demonstrate the sensitivity of the method for monitoring intracellular sodium. The supported MDCK cells in this system remained viable after exposure for 5 h to medium containing Dy(TPP)2(7-) at a concentration of 6 mM, as determined by trypan blue dye exclusion and by comparison of the log growth rate and ability to form domes in subsequent generations of exposed cells vs unexposed controls. PMID- 1751348 TI - Cell adhesion in Hailey-Hailey disease and Darier's disease: immunocytological and explant-tissue-culture studies. AB - The pathogenesis of Hailey-Hailey disease and Darier's disease was investigated using immunocytological and explant-tissue-culture techniques. There was breakdown of the intercellular adhesions between keratinocytes in explants from clinically uninvolved skin of patients with Hailey-Hailey disease or Darier's disease. The major desmosomal components were present in the cultures and were expressed in a punctate peripheral pattern at cell-cell contact sites, but there was diffuse staining of acantholytic cells. Plasminogen, which is expressed by basal keratinocytes in normal skin, was detected in association with suprabasal acantholytic cells in skin biopsies from these diseases. Plasminogen was reversibly displaced from the cells by 6-aminohexanoic acid, suggesting that binding is mediated by a reaction with the lysine receptor on the plasminogen molecule. Plasminogen was also detected in separating cells in explant cultures and there was cytoplasmic expression of the plasminogen activator urokinase by these cells. These abnormalities are not unique to either disease and do not account for the phenotypic differences between Darier's disease and Hailey-Hailey disease, but plasmin generation may have a role in perpetuating cell separation. PMID- 1751349 TI - Diurnal variations in lower leg subcutaneous blood flow rate in patients with chronic venous leg ulcers. AB - The blood flow rate in subcutaneous adipose tissue was measured on the lower legs of 11 patients with chronic lower-leg venous insufficiency and ulceration and in eight age-matched control subjects for 12-20 h, under ambulatory conditions, using the 133Xe wash-out technique with portable Cadmium telluride (CdTe(Cl)) detectors. In both groups, the change from an upright to a supine position at the beginning of the night period elicited an instantaneous increment in the blood flow rate of 30-40% with a decrease in the central and local postural sympathetic vasoconstrictor activity. After approximately 1 h of sleep, a considerable increase in blood flow rate was seen in both patient and control groups which persisted for nearly 100 min. In the patient group, the mean increase was 137% compared to a mean increase of 68% in the control group (P less than 0.01). The blood flow then returned to the same level as at the beginning of the night and remained stable until the subjects woke in the morning. The differences between this nocturnal hyperaemic phase and the adjacent phases were highly significant in both groups (P less than 0.0001 and P less than 0.005, respectively). The blood flow levels measured on the second day were of the same magnitude as those registered on the first day. The mean values of the wash-out rate constants (k) of the two groups were of the same magnitude in all phases of subcutaneous blood flow level, except in the hyperaemic phase, where it was significantly higher in the patient group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751350 TI - The prevalence of antinuclear antibodies in patients with apparent polymorphic light eruption. AB - Polymorphic light eruption (PLE) is a very common photosensitive disorder, the most important differential diagnosis of which is lupus erythematosus (LE). One hundred and forty-two patients with PLE were screened for circulating antinuclear (ANA), Ro and La antibodies over a 2-year period. Results were negative in 66 patients. Sixty-two patients had low-titre ANA of various patterns, ranging from trace to 1/80 without evidence of LE although one later developed subacute cutaneous LE. Fourteen had more significant findings, six with ANA ranging from 1/160 to 1/1280 but no anti-Ro antibodies, four with ANA ranging from 1/160 to 1/1280 and also with anti-Ro antibodies and four patients with anti-Ro antibodies but low-titre ANA, one of whom later developed discoid LE. Three of these 14 patients fulfilled the American Rheumatism Association criteria for the diagnosis of systemic LE, but it was not certain in any of the patients whether the PLE like rash represented cutaneous LE or coincidental PLE. However the overall 10% incidence of definite or possible LE in patients with suspected PLE suggests that all PLE patients should be screened for LE. PMID- 1751351 TI - Taking the 'sting' out of local anaesthetics. AB - In order to investigate factors influencing the discomfort caused by the injection of different lignocaine preparations, a randomized, double-blind comparison of paired injections was performed in 32 patients. In all subjects 2% plain lignocaine was found to be more painful than 0.5% plain lignocaine. Lignocaine with adrenaline 1:200,000 was found to be significantly more painful than plain lignocaine. The presence of sodium metabisulphite (the antioxidant in commercial adrenalized lignocaine) significantly increased the discomfort. Neutralization of acidic 0.5% lignocaine (pH 4.7) reduced the discomfort caused in 44% of patients, but this was not statistically significant. PMID- 1751352 TI - The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-alpha 2a and etretinate. AB - Forty-five patients with cutaneous T-cell lymphomas (CTCL), 32 with mycosis fungoides (MF) and 13 with Sezary syndrome (SS), were treated with interferon alpha 2a (IFN-alpha 2a) (6-9 x 10(6) IU daily) for 3 months. Those responding to treatment were then treated with interferon-alpha alone (6-9 x 10(6) IU three times weekly), and non-responders received a combination of etretinate (0.5 mg/kg/day) and IFN-alpha 2a in similar concentrations. After 12 months of treatment, 28/45 patients (62.2%) were in complete or partial (greater than 50%) remission. Of these, 17 (60.7%) were receiving IFN-alpha alone and 11 the combined interferon-retinoid therapy. Of the patients with MF stage I and II, 20/25 were responders (12 receiving IFN-alpha alone and eight on combined therapy), whereas only 8/20 with stage IV or SS responded to treatment (five receiving IFN-alpha 2a alone and three combined therapy). These results suggest that the association of etretinate with low-dose recombinant IFN-alpha 2a is an effective means of treating epidermotropic CTCL, particularly in the early stages. PMID- 1751353 TI - Necrolytic migratory erythema without glucagonoma: the role of dietary essential fatty acids. PMID- 1751354 TI - Psoriasis induced by interferon-alpha. AB - Recombinant human interferon-alpha has been used in the treatment of several cancers, but there have been several reports that it may exacerbate psoriasis or trigger off its onset. We report four patients, three of whom first developed psoriasis and one who had an aggravation of the condition during treatment with interferon-alpha. Three of the patients had the carcinoid syndrome and one a renal carcinoma, and all were treated with interferon-alpha 2b or 2a (IFN-alpha 2b, 2a) with doses ranging from 1.5 x 10(6) U daily to 18 x 10(6) U three times weekly. In two of the patients there appeared to be a correlation between the severity of the psoriasis and the dosage of interferon. PMID- 1751355 TI - Neurilemmomatosis. PMID- 1751356 TI - Pulmonary capillary leak syndrome complicating generalized pustular psoriasis: possible role of cytokines. AB - Two cases are reported of generalized pustular psoriasis complicated by profound alterations in pulmonary capillary permeability. Several features suggest the involvement of cytokines in the pathogenesis of this condition. PMID- 1751357 TI - Eruptive vellus hair cysts with sebaceous glands. AB - A patient is described who had eruptive vellus hair cysts with and without sebaceous glands in the cyst walls. An association is suggested between eruptive vellus hair cysts and the condition of steatocystoma multiplex. PMID- 1751358 TI - Hereditary epidermolytic palmoplantar keratoderma with knuckle pad-like lesions over the finger joints. PMID- 1751359 TI - Generalized hair follicle hamartoma with a positive anti-acetylcholine receptor antibody. PMID- 1751360 TI - Chronic cutaneous graft-versus-host disease: successful treatment with UVB. PMID- 1751361 TI - Clearing of pyoderma gangrenosum by intralesional cyclosporin A. PMID- 1751362 TI - Placental lactogen is a haemopoietic hormone. AB - The anaemia and thrombocytopenia of hypophysectomized (Hypox) rats could be corrected readily by daily treatment with human placental lactogen. Spontaneous DNA synthesis in the bone marrow of Hypox rats was grossly impaired, which was also normalized by placental lactogen. Human placental lactogen exerted a direct mitogenic effect on rat bone marrow cells in vitro. These results indicate that placental lactogen is a potent haemopoietic hormone. PMID- 1751363 TI - Recipient origin of bone marrow-derived fibroblastic stromal cells during all periods following bone marrow transplantation in humans. AB - The bone marrow microenvironment, which is composed of fibroblasts, endothelial cells, adipocytes and macrophages, plays an important role in the haematopoiesis and lymphopoiesis by producing various cytokines. Therefore, investigation of the origin of these cells following allogeneic bone marrow transplantation (BMT) is very significant, in terms of the haematological and immunological reconstitution after BMT. We have investigated the origin of fibroblastic stromal cells in long term cultures in seven of the sex-mismatched cases. This was carried out by in situ hybridization using a Y-chromosome specific cDNA probe (PHY10), conserving the morphology of the cells. In situ hybridization analysis showed that bone marrow fibroblasts (BMF) in long-term cultures in all the sex-mismatched cases originated from the recipients. We have also performed Southern blot analysis using a PHY10 probe in the sex-mismatched cases and using a variable number of tandem repeats (VNTR) probe, which can detect DNA polymorphisms, in two fo the sex-matched cases. In addition, we have employed polymerase chain reaction (PCR) using the VNTR marker (MCT118). Although all the patients showed haemopoietic engraftment with donor cells, their BMF were found, by Southern blot analysis and PCR method, to be of the recipient origin. These data indicate that bone marrow derived fibroblastic stromal cells which proliferate in long-term cultures are not transplantable in the conditioning regimens used for allogeneic BMT in humans. PMID- 1751364 TI - Drug-induced agranulocytosis: prognostic factors in a series of 168 episodes. AB - The prognostic value of 36 clinical and analytical parameters at diagnosis in patients with drug-induced agranulocytosis was analysed in an adult population. This multicentre, retrospective study examined possible prognostic factors by multiple logistic regression analysis in a series of 168 clinical episodes. The overall mortality was 16%. Renal insufficiency at diagnosis and the development of bacteraemia were associated with a poor prognosis. Advanced age, decreased leucocyte count, lymphocytopenia, bone marrow myeloid hypoplasia, increased percentage of bone marrow plasma cells and shock were found to be associated with a poor prognosis only in the univariate analysis. An independent analysis of the myeloid cellularity at diagnosis showed an inverse correlation with the time to recovery of the granulocyte counts (r = -0.43; P = 0.001). Our data indicate that despite some important clinical differences (higher incidence of infections of the oropharynx, shorter period of neutropenia and almost exclusive presence of gram-negative organisms), the infections complicating the treatment of cancer patients have the same prognostic features than those seen in patients with acute agranulocytosis. Therefore the established therapeutic guidelines for neutropenia after cancer chemotherapeutic agents are applicable to patients with acute agranulocytosis. PMID- 1751365 TI - IL-2 abolishes fibroblast proliferation in long-term bone marrow culture by inhibition of an accessory cell. AB - Addition of interleukin-2 (IL-2 (greater than 250 U/ml) during the first 3 d of long-term bone marrow culture (LTBMC) permanently abolished the fibroblast component of the stromal layer, even when IL-2 was removed after the 3 d culture period. When IL-2 was added at more than 72 h after initiation of culture, no effect was observed. Stromal growth in IL-2-treated culture was restored by addition of irradiated bone marrow, indicating that the IL-2 inhibited an accessory cell rather than the fibroblast directly. Accessory cells were shown to be necessary for fibroblast proliferation at low cell densities and were also inhibited by IL-2. The accessory cell effect could not be replaced by LTBMC supernatants or extracellular matrix. It is suggested that these observations are relevant to the suppression of haemopoiesis observed in patients receiving IL-2. PMID- 1751366 TI - The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure. AB - The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR. PMID- 1751367 TI - Prognostic importance of Sudan Black positivity: a study of bone marrow slides from 1,386 patients with de novo acute myeloid leukaemia. AB - Analysis of bone marrow slides from 1,386 patients entered into the Medical Research Council's 8th and 9th trials in Acute Myeloid Leukaemia confirmed that features associated with differentiation in blast cells, in particular increasing Sudan Black (SB) positivity, were the most important morphological features for predicting remission achievement (P = 0.002) and hence survival (P less than 0.0001). SB positivity was also weakly predictive of remission duration (P = 0.05). A low complement of maturing granulocytes was associated with early induction death and a high percentage of blasts with shorter remissions. The few patients with acute promyelocytic leukaemia (FAB M3) had a high haemorrhagic death rate during induction and a low relapse rate. Apart from this, lineage involvement was not predictive of outcome. Multiple lineage leukaemias, in particular those with megakaryocytic and/or erythroid involvement, which had been reported previously to have a poor prognosis, did not have any worse remission rates in this series. When more than one cell line was involved, no combination with particularly good or poor prognosis could be identified. Multivariate analysis suggested that percentage SB positivity was adequate on its own to divide granulocytic leukaemias into poorly differentiated (less than 50% SB +ve) and well-differentiated groups (50% or more SB +ve) without the need for further measurements. This simple and reproducible test was strongly predictive of resistant disease but not of induction deaths. It was of considerably greater prognostic value--and was less open to inter-observer disagreement--than the FAB criteria which are usually used to classify granulocytic lineage leukaemias into the M1 and M2 subgroups. It is proposed that greater than or equal to 50% of blasts with SB positivity should replace blasts greater than 10% of maturing myeloid cells for this sub-categorization between M1 and M2. PMID- 1751368 TI - Immunophenotypic, genomic and clinical characteristics of blast crisis of chronic myelogenous leukaemia. AB - We have studied phenotypic and clinical features in a consecutive series of 45 patients with chronic myelogenous leukaemia (CML) in blast crisis (BC). In addition, in 22 of these patients we have analysed the genotypic characteristics including immunoglobulin, T-cell receptor (TCR) and major breakpoint cluster region (M-bcr) gene organization. The granulomonocytic and megakaryoblastic lineages are the most commonly involved in these BC of CML (33% and 33% of cases, respectively); only 18% of our cases displayed a lymphoid phenotype. Moreover, both morphological and immunophenotypic studies revealed the frequent coexistence of two or three cell populations, especially when the megakaryoblast component is involved. The lymphoid BC displayed the highest incidence of complete remissions although this was not associated with a longer survival. Only minor differences between the different myeloid subgroups were observed. Immunoglobulin heavy chain (IgH) gene rearrangement was found in five of the six lymphoid BC and in one myeloid BC. Only one case showed k light chain gene rearrangement. In all but one myeloid BC the TCR-beta gene was in germline configuration. The TCR-gamma gene was rearranged in all lymphoid and one myeloid BC, while TCR-delta gene rearrangement was detected in 67% and 16% of the lymphoid and myeloid BC, respectively. Most of the lymphoid BC (4/5) had the M-bcr breakpoint in subregion 3, while the myeloid BC had the breakpoint either in subregion 2 or 3. No differences between the different myeloid phenotypic subgroups were observed in relation to breakpoint. PMID- 1751369 TI - Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia. AB - We have prospectively evaluated a regimen of mitozantrone and cytosine arabinoside (Ara-C) as first-line therapy in elderly patients with acute myeloid leukaemia (AML). One hundred and four patients with a median age of 68 (range 60 81) were studied, in whom 86 had de-novo AML, and 18 had preceding myelodysplasia or secondary AML. Complete remission was achieved in 64% of de-novo cases, in 28% of MDS/secondary cases, and in 58% overall. The incidence of early death within 28 d of chemotherapy was 11%. The median disease-free survival (DFS) was 11 months with an actuarial DFS of 15% at 43 months. The median overall survival was 9 months with an actuarial survival of 10% at 44 months. The incidence of non haematological toxicity was acceptably low, and usually of mild to moderate severity. Quality of life was improved, or unchanged, in 90% of responders. We conclude that mitozantrone and ara-C is an effective and well-tolerated regimen which produces high remission rates in elderly patients with AML. PMID- 1751370 TI - Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). AB - The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less than 2.74 mmol/l), lactate dehydrogenase (LDH) value of up to 1.5 x the normal upper limit, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone and gastrointestinal tract, and neither ascites nor pleural effusion. Skin and pulmonary lesion(s) may be present. In case of less than 5% abnormal T-lymphocytes in PB, at least one of histologically-proven skin and pulmonary lesions should be present. (2) Chronic type, absolute lymphocytosis (4 x 10(9)/l or more) with T-lymphocytosis more than 3.5 x 10(9)/l, LDH value up to twice the normal upper limit, no hypercalcaemia, no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion. Lymphadenopathy and involvement of liver, spleen, skin, and lung may be present, and 5% or more abnormal T-lymphocytes are seen in PB in most cases . (3) Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and histologically-proven lymphadenopathy with or without extranodal lesions. (4) Acute type, remaining ATL patients who have usually leukaemic manifestation and tumour lesions, but are not classified as any of the three other types. A total of 818 ATL patients with a mean age of 57 years, newly diagnosed from 1983 to 1987, were analysed by this criteria. There were 448 males and 370 females, and 253 were still alive with a median follow-up time of 13.3 months from diagnosis, while 565 were dead with a median survival time (MST) of 5.4 months. MST was 6.2 months for acute type, 10.2 months for lymphoma type, 24.3 months for chronic type, and not yet reached for smouldering type. Projected 2- and 4-year survival rates were 16.7% and 5.0% for acute type, 21.3% and 5.7% for lymphoma type, 52.4% and 26.9% for chronic type, 77.7% and 62.8% for smouldering type, respectively. Distinct clinical features and laboratory findings of each clinical subtype are described. PMID- 1751371 TI - Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM-CSF. AB - Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) expression with a cell-free enzyme-linked immunosorbent assay (ELISA) system (T Cell Sciences; Cambridge, U.S.A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA), 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL-2R levels between RA (median 368 U/ml). RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected. Six patients, who had been under treatment with rhGM-CSF for at least 2 weeks, demonstrated a three- to sevenfold increase of sIL 2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL-2R expression begins within 4 h after subcutaneous application of GM-CSF and reaches its maximum after 12 h. Our data cannot suggest whether increased sIL-2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM-CSF in MDS may result in improvement of altered lymphocyte function. As GM-CSF induces sIL-2R expression, a down regulation of the immune response caused by neutralization of free IL-2 cannot be excluded. PMID- 1751372 TI - Thrombocytopenia in acute leukaemia patients treated with IL2: cytolytic effect of LAK cells on megakaryocytic progenitors. AB - In vivo administration of recombinant interleukin 2 (IL2) has been associated, in acute leukaemia as well as in other tumours, with a variable degree of thrombocytopenia. In two patients with acute myeloid leukaemia who showed a progressive and severe fall in platelet count during daily continuous i.v. infusion of IL2, we assessed whether peripheral blood IL2-generated lymphokine activated killer (LAK) lymphocytes could affect growth of the autologous bone marrow megakaryocytic progenitor cell compartment (CFU-MK) in vitro. Following overnight pre-incubation in liquid culture of the marrow cells with autologous LAK effectors, there was an almost complete abrogation of the CFU-MK colony growth (97% and 89% inhibition). Pre-incubation in the presence of a monoclonal antibody to tumour necrosis factor alpha (TNF) completely reversed the inhibitory effect. The role played by TNF was confirmed by the finding that recombinant TNF caused a dose-dependent inhibition of the growth of CFU-MK. IL2 alone was ineffective. These results suggest that the often severe thrombocytopenia observed in patients with acute leukaemia treated with IL2 is at least partly due to autologous LAK cells activated in vivo following the administration of IL2. PMID- 1751373 TI - Consistently normal CD4+, CD8+ levels in haemophilic boys only treated with a virally safe factor VIII concentrate (BPL 8Y) AB - Prospective biochemical, virological and selected immunological follow up has been done for up to 32 months on 15 previously untreated haemophilic boys following treatment with an intermediate purity dry heated factor VIII concentrate (BPL 8Y). Tests for liver function and antibodies to blood-borne viruses have been assessed monthly for the first year after starting treatment and thereafter every 2 months. All patients were immunized against hepatitis B and have not developed hepatitis B core antibodies and no boy has shown any rise in alanine transaminase level nor has anyone developed antibodies to hepatitis C (HCV). All patients have remained anti-HIV seronegative. T lymphocyte subsets have been measured approximately every 4 months and in no patient has there been a significant rise in CD8+ cells; one patient showed a significant decrease in CD4+ cells but these and all CD4+ values for the other boys remained within normal age related limits. Changes in CD4+ levels in this one boy were not related to the total amount of treatment received. This group of patients who appear not to have contracted HIV, hepatitis B or non A non B hepatitis following treatment with this intermediate purity factor VIII concentrate have also not shown any consistent changes in CD4+ or CD8+ cells, which have been recorded previously in frequently treated haemophiliacs. PMID- 1751374 TI - An alloimmunized, thrombocytopenic patient successfully transfused with acid treated, random-donor platelets. AB - Alloimmunized, thrombocytopenic patients, refractory to random-donor platelet transfusion, often respond to HLA-identical single-donor platelets. HLA compatible platelets are expensive, take time to prepare, and donors are sometimes not to be found. We have used random-donor platelets and 'peeled' the HLA-antigen off the platelets, using a modified laboratory method (incubation of platelets with citric acid solution at 0 degrees C). Platelet recovery in two healthy subjects was 72.0% for acid-treated platelets, and 73.5% for untreated control platelets, using 111In-labelled autologous platelets. Survival time (multiple hit) was 6.25 and 7.95 d, respectively. Random-donor platelets that were strongly positive in the crossmatch with serum from a patient became negative after treatment with the acid solution. Furthermore, transfusion of these platelets gave a post-transfusion, platelet-count increment comparable with transfusion of HLA-compatible single-donor platelets. PMID- 1751375 TI - A cathepsin-like cysteine proteinase proaggregating activity in thrombotic thrombocytopenic purpura. AB - The platelet aggregating activity (PAA) of serum and plasma from thrombotic thrombocytopenic purpura (TTP, eight patients) and haemolytic uraemic syndrome (HUS, three patients) was investigated. Sample-induced aggregation of washed platelets and the parallel 3H-serotonin release were studied both in the presence and the absence of purified von Willebrand factor (vWF) or defibrinated cryoprecipitate, according to Kelton et al (1987). All the samples but two were positive in the test, vWF being indispensable for aggregation in all but two of the active cases. Samples from five patients during remission were ineffective under the same conditions, as were 14 controls from healthy donors. An inhibition study using four cysteine proteinase inhibitors (1 mM iodoacetamide, 0.5 mM E-64, 0.1 mM antipain and 0.1 mM leupeptin) and two serine proteinase inhibitors (200 U/ml aprotinin and 0.2 U/ml hirudin) confirmed that TTP/HUS's PAA behaved enzymatically as a cysteine proteinase, as described (Murphy et al, 1987a). These results were confirmed on a protein preparation obtained from pooled plasmas after Al(OH)3 adsorption, ammonium sulphate precipitation, binding to and elution from a p-(chloromercuri)benzoate (PCMB) affinity resin. To further characterize this activity we investigated whether it was a calcium-dependent neutral protease or a lysosomal cathepsin by testing the sensitivity to a series of peptidyl diazomethyl ketones, synthetic inhibitors specifically designed for cysteine proteinases. We confirm here the presence of a circulating platelet aggregating cysteine proteinase in TTP/HUS and provide evidence for the first time that this activity behaves like a lysosomal cathepsin. PMID- 1751376 TI - Abnormal low and high density lipoproteins in homozygous beta-thalassaemia. AB - The levels, structure and composition of plasma lipoproteins were determined in 67 patients with homozygous beta-thalassaemia and compared to healthy or heterozygous members of the same families and to patients with either sickle cell or iron deficiency anaemia. Plasma total and LDL and HDL cholesterol levels were low in patients with homozygous beta-thalassaemia and with sickle cell anaemia. Plasma triglycerides did not differ between subjects. The low plasma and lipoprotein cholesterol was independent of age, transfusion requirements and splenectomy. Abnormal structure and composition of lipoproteins was found in homozygous beta-thalassaemia. The LDL was of higher density and was triglyceride rich and cholesterol ester-poor. HDL separated to three populations. HDL2 was prominent (in spite of low plasma HDL cholesterol). HDL3 was of normal density and an intermediate HDL population, not found in normal subjects, was identified and designated HDL2-3. All three HDL populations were enriched with triglycerides and poor in cholesterol ester content. The modified LDL and HDL particles may then be possibly cleared rapidly from the plasma by activated monocytes and macrophages. PMID- 1751377 TI - Diagnosis of paroxysmal nocturnal haemoglobinuria using immunophenotyping of peripheral blood cells. AB - Paroxysmal nocturnal haemoglobinuria (PNH) is now generally accepted as a disease in which bone marrow derived cells are deficient in phosphatidylinositolglycan (PIG)-anchored surface molecules. A series of new monoclonal antibodies detecting PIG-anchored surface structures on human leucocytes (CD48, CD55, CD59) has recently been described. In the present study 12 patients with the diagnosis PNH and a positive Ham test were examined for PIG-anchored surface antigen expression on various cell lineages using immunofluorescence. In all patients deficient cells were detected in erythrocyte, granulocyte and monocyte analysis. A deficient lymphocyte subset was also observed in all but one of these patients. Using two-colour analysis, all lymphocyte subpopulations such as T, B and NK cells were found to be affected. In addition, peripheral blood cells of 22 patients with severe aplastic anaemia (SAA) were tested for the PIG-anchoring defect. In five of these patients the defect was detected, and in four of the five the lack of PIG-anchored molecules was confined to the granulocyte and monocyte lineages apparently without affecting the erythrocytes. The results of these studies demonstrate that cytofluorographic testing of peripheral blood cells provides a simple and reliable method for establishing the diagnosis of PNH. Furthermore, especially in the case of aplastic anaemia patients, the sensitivity of immunophenotyping might be superior to conventional laboratory tests. PMID- 1751378 TI - Lewis antigen expression in benign and malignant tissues from RBC Le(a-b-) cancer patients. AB - Eight red blood cell (RBC) Le(a-b-) individuals were selected from a series of patients with bladder or colon cancer. Defined by the presence or absence of alpha 1-4-L-fucosyltransferase activity in saliva, four of these patients were characterized as non-genuine Lewis negative [RBC Le(a-b-) with alpha 1-4-L fucosyltransferase activity in saliva], and four as genuine Lewis negative [RBC Le(a-b-) with no alpha 1-4-L-fucosyltransferase activity in saliva]. Stainings of paraffin embedded formalin fixed tissue sections for Lea and Leb antigens were performed by means of an indirect immunohistochemical method on all malignant and benign tissue previously removed from these eight patients. Leb antigens were always expressed independently of both the Lewis and the secretor status of the individual. Lea antigens, on the other hand, showed a different staining pattern. Although primarily expressed in non-genuine Le(a-b-) individuals, Lea antigens were expressed in genuine Le(a-b-) individuals as well--to a limited extent, but still detectable. Thus, these findings seem to show that the Lewis antigen expression is tissue dependent, and it is not possible to predict tissue Lewis antigen expression by merely examining erythrocytes or saliva. PMID- 1751379 TI - Haemorheological changes in the very short term after abstention from tobacco by cigarette smokers. AB - A study was made of the haemorheological changes that took place in the days immediately following tobacco withdrawal from cigarette smokers. In both males and females substantial and persistent reductions in blood viscosity occurred within 2 d, the fall at high shear rate corresponding to about 8% while at low shear rate it was approximately twice as much. These changes were due partly to a fall in packed cell volume (PCV), but also to reductions in total plasma protein and fibrinogen concentrations which led to reductions in plasma viscosity and rouleaux formation. These plasma protein-related changes were less pronounced in the female group. The results indicate that, even in the very short-term, abstention from cigarettes leads to substantial improvements in the haemorheological profile of heavy smokers. PMID- 1751380 TI - Comparisons of human, rat and mouse erythropoietins by isoelectric focusing: differences between serum and urinary erythropoietins. AB - Isoelectric focusing (IEF) in the pH range 2.5-5.0 has been used to compare the immunoreactive (ir) erythropoietin (Epo) in paired samples of serum and urine from three patients, two with idiopathic aplastic anaemia and one with paroxysmal nocturnal haemoglobinuria and also from three anaemic rats. Serum samples only were also examined from two further patients with aplastic anaemia and from three mice, made anaemic (like the rats) by irradiation and phenylhydrazine treatment. Most of the ir-Epo recovered after IEF was found in the pH range 2.5-3.9. For the sera, the proportion of more acidic ir-Epo with pI less than 3.0 recovered after IEF increased from human to rat to mouse. Human sera contained a greater proportion of ir-Epo with pI greater than 3.4 than rat or mouse sera. For the urines, the distribution of ir-Epo by IEF was similar between human and rat. For both species, the proportion of ir-Epo with pI less than 3.0 recovered after IEF was greater in urine than in the paired serum samples. The Second International Reference Preparation of Human Urinary Epo differed from the Epo in unextracted human urine in that there was a lower proportion of ir-Epo with pI less than 3.0. The differences observed between serum and urinary Epo are of particular interest because only the urinary form of native human Epo has ever been purified, and because this was used to compare native with rDNA-derived Epo. PMID- 1751381 TI - Dramatic improvement of pure red cell aplasia refractory to combined cyclosporine and prednisolone therapy induced by prednisolone dose escalation. PMID- 1751382 TI - Development of aggressive plasma cell leukaemia under interferon-alpha therapy. PMID- 1751383 TI - Systemic release of neutrophil elastase and tumour necrosis factor alpha following ABO incompatible blood transfusion. PMID- 1751384 TI - Haemopoiesis: a lottery or genomic determinism? PMID- 1751385 TI - Plasma erythropoietin levels in patients with acquired renal cystic disease. PMID- 1751386 TI - Malignant mastocytosis and myelodysplastic syndrome. PMID- 1751387 TI - Marrow stem cell and stroma cell function in aplastic anaemia. PMID- 1751388 TI - Differentiation of mesenchymal tissues during phallic morphogenesis with emphasis on the os penis: roles of androgens and other regulatory agents. AB - This article reviews various aspects of differentiation and growth of phallic mesodermal tissues with special reference to the os penis. In many species of certain mammalian orders the penile interior contains an os penis or baculum with bona fide bone. Mechanisms of phenotypic sex differentiation and the androgenic regulation of morphogenesis of genitourinary tracts of both sexes are first overviewed. Thereafter the various mesodermal tissues in fully developed penes and clitorides are discussed. The developmental fate of mesenchymal cells in the fetal genital tubercles is then considered in detail, including considerations of epithelial-mesenchymal interactions. The review concludes with a discussion of the possible roles of certain polypeptide growth factors acting in concert with androgenic steroids. Special emphasis is placed on the potential role of bone morphogenetic proteins in formation of the os penis in a restricted number of eutherian mammalian taxa. PMID- 1751389 TI - Extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by a benign testicular Leydig cell tumor. AB - We present an unusual case with bilateral testicular Leydig cell tumors displaying extraadrenal expression of steroid 21-hydroxylase and 11 beta hydroxylase. Histological examination of a 38-yr-old man infertile due to azoospermia showed him to have bilateral testicular Leydig cell tumors. The in vitro steroidogenic potential of the tumors and their adjacent testicular tissue was evaluated using organ culture. Tumor tissue was found to secrete deoxycorticosterone (DOC), corticosterone (B) and cortisol, which are not produced in normal adult testis, into the medium, while testicular tissue adjacent to the tumors secreted a small amount of DOC and B. Northern blot analysis with cytochrome P-450C21 complementary DNA (cDNA) and P-45011 beta cDNA as probes revealed that the tumor contained a considerable amount of mRNA for P 450C21 and P-45011 beta, while the MRNAs were not detected in the testicular tissues adjacent to the tumors. It is suggested that the high local levels of estrogen and/or progesterone within the Leydig cell tumors and their adjacent testicular tissues induced extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by the tumors and their adjacent testicular tissues. PMID- 1751390 TI - Bovine adrenal cytochrome P-450(11 beta)-mediated conversion of 11-deoxycortisol to 18- and 19-hydroxy derivatives; structural analysis by 1H-NMR. AB - Incubation of 11-deoxycortisol with a cytochrome P-450(11 beta)-reconstituted system yielded, in addition to cortisol, several new steroid products. In this study, structures of the three steroid products were elucidated. Retention time of the first product (Peak 2 substance) coincided with that of authentic 18 hydroxycortisol on reverse phase HPLC. To further confirm the chemical identity of this product, the purified sample was subjected to 1H-NMR analysis. The spectrum was essentially identical to that of 18-hydroxycortisol. The retention time of the second product (Peak 3 substance) did not coincide with those of commonly occurring steroids. The one- and two-dimension 1H-NMR spectra provided strong evidence for its structure of 19-hydroxy-11-deoxycortisol. The retention time of the third product (Peak 4 substance) did not coincide with those of commonly occurring steroids. The 1H-NMR spectrum showed the presence of signals of 19-CH3 and 18-CH2 protons. There was also evidence that this product is not hydroxylated at the 11-position. Further analysis of the COSY spectra identified its structure as 18-hydroxy-11-deoxycortisol. From these results, we conclude that bovine P-450(11 beta) can catalyze the hydroxylation of 11-deoxycortisol at 11 beta-, 18- and 19-positions and produce cortisol, 18-hydroxy-11-deoxycortisol, 18-hydroxycortisol and 19-hydroxy-11-deoxycortisol. PMID- 1751391 TI - Steroidogenic enzyme activity in the hypogonadal (hpg) mouse testis and effect of treatment with luteinizing hormone. AB - The hypogonadal (hpg) mouse, which lacks circulating gonadotrophins during development, has been used (a) to determine whether initial expression of steroidogenic enzyme activity is dependent upon gonadotrophins and (b) to examine the responsiveness of these enzymes to luteinizing hormone (LH) stimulation. Activities of 17 alpha-hydroxylase, 17-ketosteroid reductase and 5 alpha reductase were very low but detectable in the hpg testis while cholesterol side chain cleavage (CSCC) activity was undetectable. In contrast, 3 beta hydroxysteroid dehydrogenase (3 beta HSD) activity was high (11% of normal testis). Treatment with LH increased CSCC and 17 alpha-hydroxylase activity more than 11-fold within 24 h. 5 alpha-Reductase activity was increased 3-fold after 3 days treatment while 17-ketosteroid reductase and 3 beta HSD activities did not respond until after 10 days of treatment. The overall increases in 5 alpha reductase (4-fold) and 3 beta HSD (6-fold) activities were low while changes in 17-ketosteroid reductase (20-fold) and, particularly, CSCC (greater than 130 fold) and 17 alpha-hydroxylase (153-fold) were more marked. Results show (1) that expression of 3 beta HSD activity may be independent of gonadotrophins, (2) that activity of 17 alpha-hydroxylase, 17-ketosteroid reductase and 5 alpha-reductase is expressed, though at low levels, in the absence of gonadotrophins and (3) that prior exposure to gonadotrophins is not required for a rapid response to LH stimulation, particularly with respect to the cytochrome P-450 enzymes. PMID- 1751392 TI - The antiglucocorticoid RU486 downregulates the expression of interleukin-2 receptors in normal human lymphocytes. AB - The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 microM (28 +/- 2% of control, P less than 0.001) and on the high affinity IL-2R at 1 microM (from 2938 +/- 74 to 437 +/- 108 binding sites per cell, P less than 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of beta-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppressive effects. PMID- 1751393 TI - 19-nor-DOC biosynthesis in the isolated perfused rat kidney. AB - 19-nor-deoxycorticosterone (19-nor-DOC) is a potent salt retaining and hypertensinogenic mineralocorticoid that is excreted in the urine. While the precursor of 19-nor-DOC, 19-oxo-DOC, is produced by the adrenal cortex, conversion to 19-nor-DOC does not occur in the adrenal gland. We have examined the hypothesis that 19-nor-DOC is synthesized from precursors in the kidney. 19 oxo-DOC was added to the perfusate of isolated rat kidney preparations (n = 5) at a concentration of 10 microM. During 1 h of perfusion following addition of 19 oxo-DOC, 71 +/- 6% of the precursor was converted to 19-oic-DOC, an immediate precursor of 19-nor-DOC, and 8.3 +/- 1.8% was converted to 19-nor-DOC. This represents the first definitive evidence that 19-nor-DOC is produced in the kidney from adrenal precursors. PMID- 1751394 TI - Quantitation of glucocorticoid receptors in bovine skeletal muscle: topographical distribution, sex effect and breed comparisons. AB - The concentration of the cytosolic glucocorticoid receptor (GR) was determined in skeletal muscles of calves in order to study possible differences in individual muscles from different parts of the body as well as the influence of sex and breed. In male and female Simmental calves the topographical distribution of GR was similar: the lowest concentrations were seen in abdominal muscle, whereas in neck, shoulder and hindleg the GR concentrations were higher; this difference was more pronounced in male than in female calves. In general, female calves had about 2-fold higher GR concentrations than males. The cytosolic cortisol concentrations were differing neither between individual muscles nor between sexes. The cortisol secretion during a 24-h sampling period 1 week prior to slaughter showed no sex difference. GR concentrations in neck muscle of female calves of four different German cattle breeds (Holstein Friesian, Brown Swiss, Simmental and German Gelbvieh) were rather similar; however, when Brown Swiss with the highest GR levels were compared to Holstein Friesian calves with the lowest concentrations, a significant difference was evident (P less than 0.05). PMID- 1751395 TI - Suppression of 5 alpha-androstane-3 beta,17 beta-diol hydroxylase activity in rat pituitary by cobalt protoporphyrin: implications for testosterone homeostasis. AB - Cobalt protoporphyrin (CoPP) administered subcutaneously to adult male rats caused a marked reduction in the conversion of 5 alpha-androstane-3 beta-17 beta diol (3 beta-adiol) to its main triol derivative (6 alpha-atriol) by homogenates of the pituitary but not of the prostate or brain (ventromedial hypothalamus and cortex). No effect in the brain was observed when this heme analogue was infused intracerebroventricularly. 3 beta-adiol hydroxylase, the enzyme responsible for the reaction and whose main function is thought to be the elimination of dihydrotestosterone and its metabolites from target tissues, was also inhibited by CoPP and SKF-525A added in vitro. The reaction was microsomal and dependent on NADPH. It is proposed that the lack of reciprocal elevation of luteinizing hormone in the face of the low testosterone levels observed following treatment with CoPP may be due, in part, to increased levels of androstanediols. These metabolites accumulate because of increased production from testosterone and decreased conversion to their triol derivatives in the pituitary. PMID- 1751396 TI - A time-dependent inactivation of aromatase by 19-oxygenated androst-4-ene-3,6,17 triones. AB - 19-Hydroxyandrost-4-ene-3,6,17-trione (19-OHAT), its 19-oxo derivative (19-oxo AT) and 4 beta, 5 beta-epoxyandrostane-3,6,17-trione (5) were synthesized as possible intermediates involved in a mechanism-based inactivation of aromatase caused by androst-4-ene-3,6,17-trione (AT). These compounds, inhibited the enzyme in a competitive manner with Ki's of 0.61, 7.5 and 5.1 microM for 19-OHAT, 19-oxo AT, and compound 5. The two 19-oxygenated steroids showed a time-dependent, pseudo-first order rate of inactivation of aromatase with kinact's of 0.222 and 0.076 min-1 for 19-OHAT and 19-oxo AT, respectively, while compound 5 did not. NADPH and oxygen were required for the inactivation. Androstenedione blocked the inactivation, while L-cysteine partially prevented that of 19-OHAT and almost completely that of 19-oxo AT. When the 19-oxygenated steroids were separately subjected to reaction with N-acetyl-L-cysteine, these rapidly disappeared from the reaction mixture with t1/2 of 25 min (19-OHAT) and 20 s (19-oxo AT). This finding indicates that L-cysteine prevents inactivation by a chemical dependent elimination of the inhibitors from the incubate. These results suggest that the 19-oxygenation rather than the 4,5-epoxidation may be involved in the time dependent inactivation by AT. PMID- 1751397 TI - In vitro effect of synthetic progestogens on estrone sulfatase activity in human breast carcinoma. AB - The effect of progesterone and nine synthetic progestogens on the activity rate of microsome estrone sulfatase obtained from human breast carcinoma tissues was studied. The progestogens were classified into three groups: group I with a strict inhibitor effect: demegestone and chlormadinone acetate; group II with a strict activator effect: medroxyprogesterone acetate, quingestanol acetate, lynestrenol and progesterone and group III with a nonsignificant effect: dydrogesterone, promegestone, norgestrel and danazol. Demegestone was the most potent inhibitor and medroxyprogesterone acetate and quingestanol acetate had the highest activator effect. The effect of Triton X-100, a nonionic detergent, was also tested. This detergent consistently increased the microsome estrone sulfatase activity. A comparison was made between the effects of demegestone, medroxyprogesterone acetate and danazol on estrone sulfatase activity measured with or without Triton X-100 in the incubation medium. The presence of the detergent modified the progestogen action. Our results suggest that synthetic progestogens can influence the estrone sulfatase activity measured in human breast carcinoma tissues. However, the effect of progestogens was dependent on experimental conditions. Progestogens such as demegestone and chlormadinone acetate which inhibited estrone sulfatase activity in intact preparations, can reduce the intracellular production of biological active estrogen via the sulfatase pathway. PMID- 1751398 TI - In vivo and in vitro studies on sex steroid binding protein (SBP) regulation in rainbow trout (Oncorhynchus mykiss): influence of sex steroid hormones and of factors linked to growth and metabolism. AB - The respective roles of sex steroids and hormones related to growth and metabolism, on SBP regulation have been studied in rainbow trout. In vivo, oestradiol (E2) supplementation induces a slow but significant increase of plasma SBP concentration. Testosterone or cortisol injections have no effect. In vitro, the steroid binding protein that accumulates in incubation medium of hepatic cell primary cultures has been characterized and found to be similar to blood SBP. Its production is increased by addition of E2 (maximum: +300%). This effect develops slowly over several days of culture and is dose dependent; as little as 1-10 nM E2 is effective. Recombinant rainbow trout GH (rtGH)--0.01 to 1 microgram/ml- also increases SBP accumulation as compared to control cells and seems to maintain SBP production over culture duration. In preliminary experiments, (1) insulin-like growth factor (IGF) and SBP concentrations were found to change inversely after a 4 days stimulation with increasing concentrations of GH; (2) recombinant human IGF1 (250 ng/ml) tended to be inhibitory when SBP production was expressed per mg of total cellular protein, and a micromolar concentration of bovine insulin was clearly inhibitory. Other hormones tested in vitro: triiodothyronine (10-1000 nM), thyroxine (100 nM), 17 alpha, 20 beta dihydroprogesterone (10-2000 nM), and testosterone (1-1000 nM) did not influence SBP concentration in hepatic cells culture media. PMID- 1751399 TI - DNA ploidy pattern of parathyroid parenchymal cells in renal secondary hyperparathyroidism with relapse. AB - The nuclei of parathyroid parenchymal cells, analyzed using image cytometry (ICM), in relapsing and non-relapsing secondary hyperparathyroidism due to uremia, showed a DNA-distribution pattern of diploid type. Nevertheless, some differences were observed within the groups, as regards the concept of 'scattered cells' in ICM DNA histograms. The relative incidence of 'scattered cells' was particularly high in the histograms from parathyroid glands with nodular hyperplasia and in those from parathyroid parenchyma grafted into the skeletal musculature. In these two kinds of parathyroid specimens, the 'scattered cells' were both of chief-cell and oxyphil-cell types. In contrast, 'scattered cells' were not so conspicuous when parenchymal cells of glands with diffuse hyperplasia were analyzed. As there is some clinical and histopathological evidence that the cells in both nodular-hyperplastic and autografted parathyroid parenchyma have increased growth potential, it is hypothesized that the relative incidence of the 'scattered cells' in the ICM DNA histograms indicates an increased proliferative activity. PMID- 1751400 TI - Stage related morphometry of sarcoid granulomas and inflammatory cell types in broncho-alveolar lavage. AB - The epithelioid granulomas, interstitial and intra-alveolar mononuclear inflammatory infiltrates and the cellular compartments obtained by broncho alveolar lavage (BAL) were measured in 40 patients with pulmonary involvement of sarcoidosis. The granulomas were divided into a central (epithelioid-cellular) zone and into a peripheral (lymphocytic-fibrotic) zone, and the density of various inflammatory cells was measured in both compartments. The cases were grouped and analyzed according to the radiological and clinical stages. The results are as follows: neutrophilic granulocytes seen in the BAL probably originate from the sarcoid granulomas in patients with stage 1 of the disease and may derive from other compartments of the lung parenchyma in patients with stage 2 or stage 3. Lymphocytes seen in the BAL of patients with stage 1 or stage 2 of the disease probably derive from intra-alveolar lymphocytic agglutinations. They originate from the sarcoid granulomas only in patients with stage 3. Macrophages seen in the BAL probably derive from the sarcoid granulomas independent from the stage of sarcoidosis. No relationship was found between the morphometric parameters and the clinical outcome of the disease. PMID- 1751401 TI - Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer. AB - An immunohistological study of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) was made with 157 specimens of stomach cancer. EGF stained positively in 70 specimens (45%), and EGFR in 53 specimens (34%). The cancers were classified into three groups; Group 1 with neither EGF nor EGFR staining positively (67 tumors); Group 2 with either EGF or EGFR staining positively (57 tumors); and Group 3 with both EGF and EGFR staining positively (33 tumors). The incidence rates of tumors of macroscopically infiltrative, poorly differentiated, deep invading and node-positive types were significantly higher for Group 3 than for Groups 1 and 2. The bromodeoxyuridine labeling indices (BrdU LIs) were significantly higher for Group 3 (median: 15.1%) than for Group 1 (median: 10.7%) or Group 2 (median: 11.4%). Patients with synchronous expression of EGF and EGFR (Group 3) had the poorest prognosis. From the results, it may be concluded that tumors with synchronous expression of EGF and EGFR have the highest malignant potentials and this phenomenon may cause autocrine secretion for self replication. PMID- 1751402 TI - Use of nuclear image cytometry, histopathological grading and DNA cytometry to make breast cancer prognosis more objective. AB - Feulgen-stained tissue sections of 187 invasive ductal carcinomas (94 with lymph node metastases; mean follow-up: 44 months) were studied using computer assisted image cytometry. Based on survival time, the prognostic significance of nuclear image analysis was compared with the results using conventional histopathological grading according to Bloom and Richardson, as well as with image cytometric DNA measurements. The histopathological grading has the disadvantage of poor interobserver reproducibility (71.1%). Despite statistically significant differences between the actuarial survival curves of grade 1 and grade 3 patients, the prognostic significance of the conventional grading method for individual patients seems to be low and the number of grade 2 cases (42.8%) is large. The quantitative morphological method for analyzing nuclear images gives more reproducible results. Compared to histopathological grading, the predictive values for good or poor prognosis are clearly higher and the number of cases with uncertain prognosis is significantly smaller (20.9%). DNA ploidy measurements also make it possible to distinguish statistically significant differences between favorable and unfavorable prognoses with respect to over-all survival time. However, the classification accuracy based on the best single parameter (DNA-histogram type according to Auer) is 70.2% compared with 78.9% for nuclear image analysis. PMID- 1751403 TI - Selected bibliography. PMID- 1751404 TI - The role of jun and fos gene family members in 12-O-tetradecanoylphorbol-13 acetate induced hemopoietic differentiation. AB - Terminal differentiation of the leukemic cell lines U-937 and HL-60 by 12-O tetradecanoylphorbol-13-acetate is accompanied by marked changes in gene expression. In this study, we demonstrate that the expression of jun and fos gene family members is induced with variable kinetics during 12-O-tetradecanoylphorbol 13-acetate induced differentiation, with c-jun expression best paralleling differentiation. The generation of AP-1 complexes, as measured by DNA binding activity, closely parallels morphological differentiation. Furthermore, the ability of these complexes to regulate gene expression is demonstrated by increased transcription from an AP-1 driven reporter construct and marked increases in the expression of endogenous AP-1 regulated genes. Differentiation assays using water soluble phorbol esters reveal that differentiation becomes irreversible soon after AP-1 appears. This tight correlation between c-jun expression, the generation of AP-1 activity, and differentiation suggests a critical role for this gene and transcriptional complex during this process. PMID- 1751405 TI - Retinoic acid negatively regulates p34cdc2 expression during human neuroblastoma differentiation. AB - p34cdc2 is a protein kinase that has an important role in controlling cell cycle progression and may regulate tumor suppressor gene activity. In this work, we show that the arrest of cell growth and induction of differentiation in a tumorigenic neuroblastoma cell line by retinoic acid (RA) is associated with a 75 fold decrease in the level of p34cdc2 protein. The RA induced decrease in p34cdc2 levels does not simply reflect the arrest of cell growth, because p34cdc2 levels are not reduced when neuroblastoma cells are growth arrested by nutrient deprivation. Furthermore, dephosphorylation of the tumor suppressor gene product RB, a substrate for the p34cdc2 kinase activity, is observed only when p34cdc2 levels are decreased in RA treated cells. These studies link regulation of cdc2 level, RB phosphorylation state, and induction of differentiation by RA and suggest that alterations in the cdc2 gene or in genes controlling its regulation contribute to tumorigenesis. PMID- 1751406 TI - Decrease of proliferation rate and induction of differentiation by a MYCN antisense DNA oligomer in a human neuroblastoma cell line. AB - The effects of an antisense oligodeoxynucleotide to codons 2-7 of the oncogene MYCN on the human neuroblastoma cell line LAN-5 were studied. Treated cells showed a decreased MYCN protein expression and synthesis by immunoperoxidase staining and immunoprecipitation. At the same time, the replication rate was inhibited, and the phenotype was modified toward a more differentiated type. Our data suggest the involvement of oncogene MYCN in both proliferative and differentiative processes. PMID- 1751407 TI - A melanoma octamer binding protein is responsive to differentiating agents. AB - Analysis of human melanocytes and melanoma cell lines for proteins interacting with the octamer control sequence (ATGCAAAT) has revealed two distinct melanoma octamer binding proteins, Oct-M1 and Oct-M2. The latter was restricted to cell lines derived from tumor metastases. The level of Oct-M1 activity in a pigmented melanoma line was enhanced in comparison to the general octamer binding protein Oct-1 when cells were cultured in the presence of the depigmenting agent dithiothreitol and conversely was reduced by the differentiating and pigment inducing agents butyric acid and dimethyl sulfoxide. PMID- 1751408 TI - Joints in the regulatory lattice: composite regulation by steroid receptor-AP1 complexes. PMID- 1751409 TI - The network of hemopoietic regulatory proteins in myeloid cell differentiation. AB - There are clones of myeloid leukemic cells that can be induced to undergo terminal cell differentiation to macrophages by normal hemopoietic regulatory proteins. Induction of differentiation in two different clones of myeloid leukemic cells with interleukin 6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) resulted in induction of mRNA for the hemopoietic regulatory proteins IL-6, GM-CSF, interleukin 1 alpha and interleukin 1 beta, tumor necrosis factor, and transforming growth factor beta 1. In one of these clones, induction of differentiation with GM-CSF was also associated with induction of mRNA for macrophage colony-stimulating factor (M-CSF) but not for the receptor for M-CSF (c-fms), whereas in the other clone, induction of differentiation with IL-6 was associated with induction of mRNA for both c-fms and M-CSF. The clones also differed in their responsiveness to these regulators. There was no induction of mRNA for granulocyte colony-stimulating factor or interleukin 3 during differentiation of either clone. The results indicate that the genes for a nearly normal network of positive and negative hemopoietic regulatory proteins are induced during differentiation of these myeloid leukemic cells and that there are leukemic clones with specific defects in this network. PMID- 1751410 TI - Overexpression of the retinoblastoma gene in a familial adrenocortical carcinoma. AB - Tumors derived from a Li-Fraumeni syndrome cancer-susceptible family were examined for expression of the retinoblastoma susceptibility gene (RB). Whereas RB expression was normal in a primary breast carcinoma and its metastases from one member of this family, overexpression of RB was found in an adrenocortical carcinoma from another family member. This was in contrast to normal RB expression in normal tissue of this patient, the adrenocortical adenocarcinoma cell line SW-13, and the fibroblast cell line MRC-5, and low level RB expression in normal adrenal tissue. The overexpression in the adrenocortical carcinoma resulted in increased synthesis of the RB-encoded protein and did not appear to be associated with RB amplification or rearrangement. This result is novel as it is usually the loss of expression or production of an altered RB transcript exhibiting deletions that is associated with carcinogenesis. In light of the recent discovery of p53 point mutations in the affected Li-Fraumeni syndrome family members tested, RB overexpression may constitute a secondary event in Li Fraumeni syndrome tumorigenesis. PMID- 1751411 TI - Cloning, sequencing, and expression of two Xenopus laevis c-ets-2 protooncogenes. AB - In a general approach to identify genes important in the control of genetic expression during development of Xenopus laevis, two complementary DNAs corresponding to two different c-ets-2 genes were cloned and sequenced. One of these complementary DNAs appears to be almost full length. The two variant genes differ in their overlapping sequences by 87 nucleotide substitutions, leading to 17 amino acid modifications in the proteins, 8 of them being conservative. All but one of these changes map outside of the 142 COOH-terminal residues, a region critical for nuclear localization and DNA binding in the ets proteins. Features potentially important for the biological activity of the gene products are conserved. Two transcripts (3.2 and 1.7 kilobases) with maternal characteristics are detected at a constant level from stages II/III of oogenesis to stage 10 of embryogenesis. They later decline to hardly detectable levels at stages 30-40. Variable amounts of the same transcripts are observed in many adult tissues. All of these characteristics support the idea that the ets-2 gene products play an important role during embryogenesis, as well as in adult life. Indeed, they act as ubiquitous transcriptional activators, as recently demonstrated by several investigators (C. V. Gunther, J. A. Nye, R. S. Bryner, and B. J. Graves, Genes & Dev., 4: 667-679, 1990; R. Bosselut, J.F. Duvall, A. Gegonne, M. Bailly, A. Hemar, J. Brady, and J. Ghysdael, EMBO J., 9: 3137-3144, 1990; R. Wasylyk, C. Wasylyk, P. Flores, A. Begue, D. Leprince, and D. Stehelin, Nature (Lond.), 346: 191-193, 1990). PMID- 1751412 TI - Immunohistochemical localization of retinal serotonin cells in the lamprey (Lampetra fluviatilis). AB - Light-microscopic immunocytochemistry was used to study serotonin (5HT) containing retinal cells in the lamprey (Lampetra fluviatilis). Observations of sections and flatmounted retinas enabled us to distinguish four principal types of 5HT-immunoreactive neurons, on the basis of the localization of their somata and the arrangement of their processes in the inner plexiform layer, (IPL). Type 1 cell bodies (9 micron mean diameter) were numerous and were found in the innermost row of the inner nuclear layer (INL). They sent their processes into a dense plexus in sublamina a of the IPL. Type 2 cell bodies (12 micron mean diameter) were observed near the inner limiting membrane, their processes forming a plexus in sublamina b of the IPL. Most of the type 3 cells were bistratified, their cell bodies (similar in dimension to type 1) were located in the INL and their dendrites projected to both plexuses. Type 4 cell bodies (15 micron mean diameter) were observed in the middle of the IPL and could be compared with the interstitial described elsewhere. Their processes probably ended in the 5HT plexus of sublamina b but because of their sinuous course in the IPL, we could not affirm this fact. Most of 5HT immunoreactive cells were thought to be amacrine cells, but the presence of some thin processes emerging either from the soma or the primary dendrite, principally in type 1 and 2 cells, raises the possibility that some ganglion cells could be 5HT immunoreactive. The organization of the 5HT processes into two plexuses located in sublaminae a and b of the IPL resemble the functional ON and OFF pathway seen in the other vertebrates. PMID- 1751413 TI - Visual performance of horseshoe crabs day and night. AB - A circadian clock modulates the structure and function of the lateral eyes of Limulus polyphemus, greatly increasing their sensitivity at night. During the mating season, male Limulus are visually attracted both day and night to females and objects that resemble females. This paper asks how well Limulus can see day and night, and whether the circadian changes in retinal sensitivity might influence the ability of these animals to find mates. We recorded the visual behavior of male and female horseshoe crabs in the vicinity of an object--a cement hemisphere (29.5 cm diameter) similar in size and shape to a female horseshoe crab--placed in a mating area near Mashnee Dike, Bourne, Massachusetts. Males oriented toward this target from an average distance of 0.94 m during the day and 0.88 m at night; and females appeared to avoid the target. We conclude that males can see potential mates at night almost as well as they can during the day. Apparently the circadian changes in the retina help compensate for the daily changes in illumination in the animal's normal environment. This study provides the first evidence for a role of visual circadian rhythms in an animal's natural behavior. PMID- 1751414 TI - Lagged Y cells in the cat lateral geniculate nucleus. AB - We report on the existence of lagged Y (YL) cells in the A laminae of the cat lateral geniculate nucleus (LGN) and on criteria for identifying them using visual and electrical stimulation. Like the lagged X (XL) cells described previously (Mastronarde, 1987a; Humphrey & Weller, 1988a), YL cells responded to a spot stimulus with an initial dip in firing and a delayed latency to discharge after spot onset, and an anomalously prolonged firing after spot offset. However, the cells received excitatory input from retinal Y rather than X afferents, and showed nonlinear spatial summation and other Y-like receptive-field properties. Three YL cells tested for antidromic activation from visual cortex were found to be relay cells, with long conduction latencies similar to those of XL cells. Simultaneous recordings of a YL cell and its retinal Y afferents show striking parallels between lagged X and Y cells in retinogeniculate functional connectivity, and suggest that the YL-cell response profile reflects inhibitory processes occurring within the LGN. The YL cells comprised approximately 5% of Y cells and approximately 1% of all cells in the A laminae. Although infrequently encountered in the LGN, they may be roughly as numerous as Y cells in the retina, and hence could fulfill an important role in vision. PMID- 1751415 TI - Localization of retinal photoisomerase in the compound eye of the honeybee. AB - The distribution of honeybee retinal photoisomerase, a soluble light-requiring enzyme that stereospecifically forms 11-cis retinal, was investigated by immunoelectron microscopy and by HPLC. Immunolocalization with polyclonal antibodies shows that the highest concentration of retinal photoisomerase is located in the proximal portion of the primary pigment cells in large aggregates (approximately 2 microns diameter). Photoisomerase is also located in the peripheral portion of the photoreceptor cells, laterally displaced from the rhabdom, but in much lower concentration. Because of the larger volume of the photoreceptor cells, about half of the total immunoreactivity is associated with the primary pigment cells. Dissection of the eye with the subsequent use of HPLC to assay for photoisomerase activity showed that most of the photoisomerase activity is associated with tissues near the cornea. The same tissue also supports the reduction of 11-cis retinal to 11-cis retinol. These biochemical findings are consistent with the immunolocalization of retinal photoisomerase to the high-concentration aggregates in the primary pigment cells that surround the crystalline cones. The major synthesis of 11-cis retinol therefore takes place in the primary pigment cells, and the retinoid must be moved into the photoreceptor cells to be available to newly synthesized opsin. The immunoreactivity of the photoreceptor cells appears to reflect the presence of some isomerase without an attached retinoid chromophore. PMID- 1751416 TI - Mechanism of anomalous retinal correspondence: maintenance of binocularity with alteration of receptive-field position in the lateral suprasylvian (LS) visual area of strabismic cats. AB - We have examined the effects of rearing kittens with a unilateral convergent strabismus, induced surgically at 3 weeks of age, on the binocularity (ocular dominance) and receptive-field position of neurons in the motion-sensitive lateral suprasylvian (LS) area of cat extrastriate cortex. Data were compared to those obtained from area 17 in the same animals, and from the two areas of cortex in normal adult cats. Interocular alignment of the operated cats was assessed in alert adults using corneal reflex photography and during recording from the positions of retinal landmarks under paralysis. The strabismus magnitude in each operated cat was calculated by comparison with equivalent data from the normal animals. Strabismus always caused a major loss of binocularity in area 17. The remaining binocular neurons had receptive-field (RF) pairs arising from positions of normal correspondence in the two retinae and would thus have been responsive to different regions of visual space through the misaligned eyes in the alert animal. In area LS, the effects were dependent on the strabismus magnitude. In the group of four cats with pronounced strabismus (18-30 deg crossed), a loss of binocularity occurred in area LS equivalent in severity to that in area 17. The majority of the remaining binocular LS neurons possessed RF pairs in normal retinal correspondence and would thus, in the alert animal, have received spatially disparate visual input through the two eyes. This also occurred in three other cats with more moderate strabismus (11-15 deg crossed), although only a small breakdown in the binocularity of area LS was apparent. The group of cats with mild strabismus (less than or equal to 10 deg crossed) had normal proportions of binocular neurons in area LS. In three of these cats, the maintenance of binocularity was accompanied by shifts in RF position, with visual inputs arising from anomalous retinal locations. These shifts compensated, in part, for the strabismus angle present in each cat, so that most of the binocular LS neurons would have received inputs from regions of visual correspondence through the misaligned eyes when the animal was alert. Similar mechanisms could afford a basis for the binocular visual compensations that occur in humans with small-angle strabismus of early onset. If so, anomalous retinal correspondence in such individuals would have as a locus areas of extrastriate cortex with a role in motion perception, and would involve alterations to the neural substrate underlying normal binocular vision. PMID- 1751417 TI - A molecular basis for Weber's law. AB - A mathematical model is presented that obeys a strong form of Weber's law--over a range of adapting and stimulus intensities, equal contrast stimuli evoke identical responses. To account for the strong Weber's law, the adaptive stage in the proposed model employs a "delayed" reverse reaction along with a power-law input. It is suggested that this Weber's law mechanism is responsible for a slow, voltage-uncorrelated component of adaptation in the vertebrate photoreceptor. A plausible biochemical mechanism is the G-protein cycle with phosphorylation of photoactivated photopigment (and binding of arrestin to the phosphorylated photopigment) as the adaptive process. In an Appendix, features of the general model and implications of a specific biochemical model are examined by computer simulation. PMID- 1751418 TI - Development of visual inhibitory interactions in kittens. AB - This study was designed to monitor the development of inhibitory interactions elicited in the cat visual system by oriented visual stimuli. Steady-state visual evoked potentials (VEPs) were recorded from the scalp of 11 behaving and alert kittens while they viewed contrast-reversed sinusoidal gratings. In adult cats, the form of VEP contrast-response curves (the amplitude of second harmonic modulation as a function of stimulus contrast) was modified by superimposing a mask grating on the test. Parallel masks displaced the curves to a higher contrast region (probably via contrast gain-control mechanisms), increasing contrast threshold without affecting the slope of the curve. Orthogonal gratings, on the other hand, decrease the slope of the curve without affecting threshold (so called cross-orientation inhibition: Morrone et al., 1981). These effects are similar to those previously reported in human VEPs (Morrone & Burr, 1986; Burr & Morrone, 1987) and single cortical cat cells (Morrone et al., 1982). For young kittens of 20 days, the orthogonal mask had no effect whatsoever on the response curves, and the effect of the parallel mask was much less than for adult cats. At about 40 days, the orthogonal mask began to attenuate responses multiplicatively, and by 50 days the amount of multiplicative attenuation had reached adult levels. The effect of the parallel mask (as indicated by the increase in threshold elevation) increased gradually from 20-50 days. The results are consistent with the existence of at least two types of inhibition in cat visual neurones that develop at different rates. PMID- 1751419 TI - Effects of monocular deprivation on the development of visual inhibitory interactions in kittens. AB - A visual-evoked-potential (VEP) masking technique was used to assess the effects of short- and long-term monocular deprivation on the development of visual inhibitory interactions in kittens. VEP contrast-response curves were recorded in response to contrast-reversed sinusoidal gratings, both with and without superimposed high-contrast masks. The contrast-response curves measured from the nondeprived eye were similar to those of normal cats: with no mask VEP amplitudes increase with contrast up to saturation at about 10% contrast; parallel masks shift the curves to the right, decreasing thresholds; and orthogonal masks decrease the slope of the contrast-response curves without affecting thresholds. After monocular deprivation (either brief or extensive), the contrast-response curves without mask did not show the typical response saturation, and neither parallel nor orthogonal mask had any effect on the contrast-response curves. The masking effects did not return after 100 days of normal vision, although contrast sensitivity and acuity recovered to about half of the normal levels during that period. The results indicate that the inhibitory intracortical circuitry that mediates the orientation-dependent masking effects are highly vulnerable to visual experience. PMID- 1751420 TI - Mechanisms of early visual processing in the medulla of the locust optic lobe: how self-inhibition, spatial-pooling, and signal rectification contribute to the properties of transient cells. AB - In the arthropod medulla, which is the second ganglion on the afferent visual pathway, a column of about 40 cells represents each point in space (i.e. compound eye facet). Some stages of visual processing underlying the responses of one class of cells in the locust medulla have been identified. These transient cells give very similar responses to intensity increments and decrements, and also to pulses and steps; there is no spontaneous activity and a stimulus causes one or two spikes to fire at fixed latencies. Movement, however, produces a prolonged spike discharge by successive excitation of subunits within the receptive field. One of the main features of the transient cells' responses is a self-inhibition which attenuates responses to successive stimuli at one point. This inhibition is restricted to the outputs of single receptor (rhabdom), it decays after about 100 ms, and is polarity sensitive so that stimuli of one polarity (e.g. dimming) do not inhibit responses to stimuli of the opposite polarity (e.g. brightening). The inhibition effectively alters the contrast threshold of the cells, because after adaptation with stimuli of one contrast, a modest (less than 20%) increase in contrast is sufficient to elicit an unadapted response. Transient cells are not directionally selective and there are no local spatio-temporal interactions of the kind necessary for directional selectivity. But, by analogy with the directional veto in directionally selective cells in the rabbit retina (Barlow & Levick, 1965), self-inhibition is suggested as a mechanism of non-directional motion detection. After the inhibition, there is some spatial pooling of signals which is followed by rectification. The transient cells' spiking outputs could abstract a refined subset of visual information which may encode the presence, but not the direction, amplitude, or polarity of moving object borders. PMID- 1751421 TI - Habituation-like decrease in the responses of neurons in inferior temporal cortex of the macaque. AB - In both anesthetized and behaving macaques, we examined the responses of neurons in the inferior temporal cortex (IT) to repeated presentation of a visual stimulus. In anesthetized animals, the responsiveness of IT neurons decreased with repeated stimulus presentation at interstimulus intervals (ISIs) of 2-12 s but not at 20 s. Responsiveness recovered after a 5-min period of no stimulus presentation. The response decrement was similar in anesthetized and awake animals at a 2-s ISI, but at a 6-s ISI, response decrement in the awake animal was much less. PMID- 1751422 TI - Physiological and morphological properties of off- and on-center bipolar cells in the Xenopus retina: effects of glycine and GABA. AB - We studied the morphology and center-surround organization of Lucifer Yellow injected OFF- and ON-center bipolar cells in the light-adapted Xenopus retina and the effects of glycine and GABA on their cone-mediated light responses. In both classes of cell, prominent antagonistic surround responses up to 20 mV in amplitude could be evoked without first suppressing the center responses with steady illumination. An additional feature of the light-evoked bipolar cell response was a pronounced (up to -24 mV) delayed hyperpolarizing after potential (DHAP) which followed the depolarizing responses of both classes of bipolar cell. The morphological features of dye-injected bipolar cells conformed to the general idea of segregation of ON and OFF pathways in the inner and outer interplexiform layer, however, the morphology of axonal arborizations was different for both classes. OFF-center cells ramified symmetrically around the primary branchpoint, whereas ON-center cells had a strongly asymmetrical arrangement of their axonal tree. The center and surround responses were differentially sensitive to glycine and GABA. Glycine eliminated the antagonistic surround responses in both OFF and ON cells; the center responses were reduced to some extent but were not eliminated. In contrast, GABA affected the hyperpolarizing responses much more strongly than the depolarizing response components. That is, the amplitude of the center response in the OFF cell and the surround response in the ON cell was reduced 80-90% during exposure to GABA, whereas the surround and center depolarizations of OFF and ON cells, respectively, were reduced only 0-10%. Our findings implicate a role for GABAergic and glycinergic pathways in the center surround organization of bipolar cells in Xenopus retina. In addition, the results suggest that the pathways mediating center-surround antagonism may be different in OFF-bipolar cells vs. ON-bipolar cells. PMID- 1751423 TI - Antibodies to human leucocyte antigens indicate subpopulations of microglia in human retina. AB - Monoclonal antibodies to human leucocyte antigens, including anti-CD45 and anti CD68, have been used to describe microglia in flatmounts of normal adult human retina for the first time. Anti-CD45 (the leucocyte common antigen) intensely labeled large numbers of cells in a regular distribution across the retina; anti CD68 and anti-macrophage antibodies labeled fewer cells with distinctive morphologies, suggesting the presence of subpopulations of microglia in the human retina expressing leucocyte antigens. PMID- 1751424 TI - Visual input to commissural neurons of the cat's superior colliculus. AB - Cells projecting into the commissure of the cat's superior colliculus were identified during extracellular recording by antidromic activation. Electrical stimulation of the ipsilateral optic tract evoked action potentials in the majority of commissural neurons. Response latencies of 1.4 +/- .5 ms (mean +/- S.D.) in a few cells indicated that some commissural neurons receive direct input from the axons of retinal Y-cells. Most commissural cells responded 5.9 +/- 1.9 ms (mean +/- S.D.) following optic tract shock, implying that the responsible pathway was composed of more slowly conducting axons or did not proceed directly to the colliculus. Results of previous studies of retinal inputs to cells in the deep tectal layers suggest that the later responses were mediated by an indirect Y pathway through the visual cortex. PMID- 1751425 TI - Directional performances with moving plaids: component-related and plaid-related processing modes coexist. AB - A moving grating oriented +/- 45 degrees to the vertical can be perceived at choice as drifting along a left-right or up-down directional axis. When the drifting stimulus is presented alone, direction discrimination thresholds are independent of the specified response-axis. However, they strongly depend on it when the moving stimulus is superimposed on a vertical or horizontal stationary grating. Facilitation is always obtained when the drift direction of the intersections of the two gratings ('blobs') is collinear with the response-axis (i.e. when the orientations of the stationary grating and of the response-axis coincide), while inhibition is observed in the 'noncollinear' cases (i.e. when the orientations of the stationary grating and of the response-axis are orthogonal). These results are generalized in a series of reaction time (RT) experiments where the stimulus configuration described above was set at suprathreshold contrasts and where the orientation/direction of the drifting grating was variable. RT increased when the angle between the response-axis and the direction of the drifting grating increased (uncertainty effect), whether the test stimulus was presented alone, or superimposed on the stationary grating. The uncertainty effect was, however, significantly decreased under 'collinearity' conditions. The attenuation of the uncertainty effect was proportional with the velocity of the blobs and about equal in amount to the RT decrease obtained through the manipulation of the velocity of the drifting grating when presented alone (velocity effect). This observation strongly suggests that both component- and blob/plaid-related information contribute to the directional perception of a compound stimulus and that they sum algebraically. PMID- 1751426 TI - Edge extraction by active defocusing. AB - A novel edge extraction method that employs an active defocusing technique is presented. The method is based on the principle that a Laplacian-of-Gaussian (LOG) operation can be approximated by a Difference-of-Gaussian (DOG) operation. While such an operation is usually done in digital image processing, it can also be very effective conducted in a combination of optical techniques and digital processing. In this edge extraction method, a focused image of an object in a scene is first acquired. The image of the scene is then slightly defocused by changing the focal length of the camera. A real time subtraction operation is applied to subtract the defocused image from the previously acquired image. It produces a residual image that emphasizes abrupt intensity variations. An objective evaluation, called an edge index, is performed on the resulting image. The amount of defocusing is carefully adjusted according to this measurement so that a desired edge image is generated. Boundaries of objects can then be obtained by further enhancement of the edge image. Since this edge detection method is an optical-based process aided by digital processing, it is fast and relatively inexpensive. PMID- 1751427 TI - The search operating characteristic as a tool for analyzing performance in dynamic visual search tasks. AB - A standard data plot for the analysis of eye movement behavior in visual search and related tasks, a Search Operating Characteristic (SOC), is proposed. The SOC plots mean fixation duration (in ms) vs. search span (in items/fixation) for different difficulty levels. It is well specified by a reciprocal power function and this function can be explained with the help of Pieron's law. PMID- 1751428 TI - Effects of adaptation to apparent movement on recovery of structure from motion. AB - Past work on the recovery of three-dimensional structure from dynamic two dimensional images has led to inconsistent conclusions regarding the contributions of the short-range and long-range motion processes. In the present experiments, subjects adapted to displays (either four lines or 50 randomly positioned pixels) whose spatiotemporal parameters were chosen to favor either the short-range or long-range process. Adaptation periods were followed by test displays that simulated the rotation of a four-pixel random object about the vertical gamma-axis. The dependent measure was the angle of rotation between successive frames of the rotation display at which percepts of three-dimensional structure broke down. Both the original data and derived measures based on best fitting polynomials showed small but consistent effects: Compared to control conditions, adaptation to short-range motion reduced the angle at which percepts of structure broke down; adaptation to long-range motion increased them. It is suggested that both low-level (i.e. short-range) and high-level (long-range) processes contribute to the recovery of structure from motion. PMID- 1751429 TI - Comments on Cavanagh and Mather (1989): coming up short (and long) AB - Cavanagh and Mather (1989) reviewed literature concerning the possible distinction between short- and long-range processes in motion perception and concluded that the distinction cannot be supported. Instead, they proposed that motion perception be considered on the basis of detectors for first-order (luminance, color) and second-order (first-order motion, texture, stereo) stimulus attributes. They supported their position with studies of motion based on second-order stimuli. The present paper contends that when experiments permitting the investigation of both processes in the same display are included and when criteria are examined in their totality rather than one-by-one, the original short-range/long-range distinction can be retained. Furthermore, it is argued that the first-order/second-order distinction does not represent a theoretical advancement and that studies of second-order motion can be interpreted in terms of the older distinction. It is concluded that the short range/long-range distinction is useful and should not be abandoned. PMID- 1751430 TI - Short-range vs long-range motion: not a valid distinction. PMID- 1751431 TI - Randomized controlled trial of antenatal social support to prevent preterm birth. AB - OBJECTIVE: To test the effect of a programme of additional antenatal social support on the occurrence of preterm birth (a birth from 20 to 36 weeks gestation) in women at risk of preterm birth. DESIGN: A prospective randomized controlled trial. The design was one of randomization before consent for a new treatment. SETTING: Three public hospital antenatal clinics in Perth and the offices of 87 obstetricians and general practitioners in Western Australia. SUBJECTS: 1970 pregnant women with poor obstetric histories entered the trial; 983 of these were randomly allocated to the programme group and 987 to the control group. INTERVENTIONS: Normal antenatal care was provided for both groups. In addition, members of the programme group were offered an intervention aimed at providing expressive (emotional) social support, consisting of antenatal home visits and telephone calls by midwives. Of the women allocated to the programme group, 24 refused consent and 69 were not traced before completion of their pregnancies, the remaining 890 women (90.5%) agreed to enter the programme, and each received at least one intervention. MAIN OUTCOME MEASURES: Gestational age at completion of the pregnancy. A pregnancy ending before 20 weeks was labelled a miscarriage. RESULTS: There were 126/981 (12.8%) preterm births in the programme group and 147/986 (14.9%) in the control group. The outcome data for two women in the programme group and one in the control group could not be found. The unadjusted odds ratio for preterm birth in the programme was 0.84 (95% CI 0.65 1.09). The observed relative reduction in preterm births associated with the programme was 13.8% (95% CI -8.2% to +31.5%) and the trial had a 60% power to exclude a true relative reduction of 25%. CONCLUSIONS: The results of this trial and those of other controlled clinical trials provide little evidence for the effectiveness of social support interventions in the prevention of preterm birth in women with poor obstetric histories. PMID- 1751432 TI - Pre-eclampsia and offspring's blood pressure, cognitive ability and physical development at 17-years-of-age. AB - OBJECTIVE: To investigate the influence of maternal pre-eclampsia on the blood pressure, physique and intelligence of the offspring at the age of 17 years. DESIGN: Data obtained at the age of 17 during assessment for drafting to the Israel Defence Forces and from the records of the mothers' pregnancies from the Jerusalem Perinatal Study. SUBJECTS: Study subjects were 145 girls and 283 boys whose mothers had had pre-eclampsia and controls were 12,701 girls and 20,416 boys whose mothers did not have pre-eclampsia. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, weight, height and intelligence scores at the age of 17 were related to birthweight and the occurrence of pre-eclampsia during their mothers' pregnancies. RESULTS: Systolic blood pressure was greater than 140 mmHg in 6.9 and 11.0% of the study girls and boys, compared with 2.9 and 9.9% of the control girls and boys. The study boys but not the girls had a higher mean body mass index than the controls (P less than 0.001). There were no differences in the intelligence scores. Using multiple logistic regression to allow for the confounding effects of body mass index, weight and birthweight, the odds ratio for the risk of a systolic pressure greater than 140 mmHg was 2.30 (95% CI 1.80 4.46) for the study girls but was not significantly increased for the study boys. CONCLUSION: Maternal pre-eclampsia does not impair growth and cognitive performance in the children who reach late adolescence but may be associated with hypertension. PMID- 1751433 TI - The effect of induced abortion on subsequent pregnancy outcome. AB - OBJECTIVE: To investigate the effect of induced abortion on the outcome of the next pregnancy. DESIGN: Long-term prospective controlled cohort study. SETTING: Joint Royal College of General Practitioners/Royal College of Obstetricians and Gynaecologists study based in general practice in England, Scotland and Wales. SUBJECTS: 1311 women whose recruitment pregnancy had ended in induced abortion (the abortion group) and 2131 women whose recruitment pregnancy had a natural conclusion (the non-abortion group). MAIN OUTCOME MEASURES: Non-viable outcome (spontaneous or missed miscarriage, ectopic pregnancy or stillbirth), birthweight, length of gestation. RESULTS: Induced abortion was not materially associated with any of the three measures of adverse outcome. Compared with the non-abortion group the relative risk of a non-viable outcome in the abortion group was 1.01 (95% CI 0.81 to 1.27). In the abortion group birthweight was an average 23 g lighter (95% CI -76 g to + 30 g) and length of gestation an average 0.9 days shorter (95% CI -2.2 days to + 0.4 days) than in the non-abortion group. Women who had their abortions in NHS premises had an increased risk of a non viable outcome (RR 2.55, 95% CI 1.31 to 4.94) and had babies with significantly lower mean birthweight (-119 g, 95% CI -233 g to +5 g) compared with those who obtained their operations in the private sector. Women whose abortion had been carried out by a consultant had the lowest risk of non-viable outcome. Although these differences remained after adjustment for a number of important variables, it is possible that factors not measured in the present study, such as economic status and occupation, played a contributory role. CONCLUSION: Overall, induced abortion was not associated with any important effect on the three measures of adverse outcome in the subsequent pregnancy. PMID- 1751434 TI - Pre-operative cervical preparation before first trimester vacuum aspiration: a randomized controlled comparison between gemeprost and mifepristone (RU 486). AB - OBJECTIVE: To compare the effectiveness of 200 mg mifepristone with 1 mg gemeprost vaginal pessary in achieving cervical dilatation and softening ('priming') before late first trimester pregnancy vacuum aspiration. DESIGN: A randomized, operator blind, placebo controlled trial. SETTING: UK teaching hospital. SUBJECTS: 90 primigravid women with 63-91 days amenorrhoea and ultrasonically confirmed single living fetus of correct size for gestational age. INTERVENTIONS: The women were allocated to receive 200 mg mifepristone orally or an identical oral placebo 36 h before operation or 1 mg gemeprost vaginal pessary 3-4 h preoperatively. MAIN OUTCOME MEASURES: Onset of new symptoms following drug administration, a proven objective measure of the force required to dilate the cervix, and estimated intraoperative blood loss. RESULTS: There were no significant differences in the baseline cervical dilatation, the force required to dilate the cervix or the volume of intraoperative blood loss between the active treatment groups. Both drugs were significantly more effective than placebo. Significantly fewer women in the mifepristone group had adverse side effects than in the gemeprost group. CONCLUSIONS: Mifepristone is a highly effective cervical priming agent, and has the advantages of being an oral preparation associated with few side effects. PMID- 1751435 TI - A clinical comparison of sonographic hydrotubation and hysterosalpingography. AB - OBJECTIVE: To assess the value of vaginal sonographic hydrotubation as a preliminary test of uterine configuration and tubal patency in infertility investigation, and to compare this new test with hysterosalpingography. DESIGN: A prospective blind comparison of the two tests in an unselected group of infertile women. SETTING: Hillbrow Hospital, Johannesburg, South Africa. SUBJECTS: Sixty women undergoing routine infertility investigations agreed to participate in the study. There were no refusals. INTERVENTIONS: Within 4 weeks before or after hysterosalpingography sonographic hydrotubation was performed as follows: The uterus and tubes were identified using a 5 MHz vaginal ultrasound probe and between 10 and 20 ml of normal saline were injected into the uterine cavity through an endocervical catheter. MAIN OUTCOME MEASURES: The shape of the uterus and its cavity, the flow of saline through the tubes, the presence of hydrosalpinges before and after injection of saline and the presence of free fluid in the pouch of Douglas. RESULTS: The sonographic and hysterosalpingographic findings were similar in 82% of the women with respect to uterine assessment and in 72% with respect of tubal findings. In seven women (12%) found to have bipolar tubal disease on sonography and cornual block on hysterosalpingography, the sonographic diagnosis was confirmed at laparoscopy. Septate uterus in three women was diagnosed with greater certainty with sonographic hydrotubation. CONCLUSIONS: Sonographic hydrotubation is a simple office procedure which should be used in the preliminary assessment of the uterine cavity and fallopian tubes. Its use will reduce the need for hysterosalpingography and in some cases laparoscopy. PMID- 1751436 TI - A new treatment for endometrial cancer with gonadotrophin releasing-hormone analogue. AB - OBJECTIVE: To test the antitumour effect of gonadotrophin releasing-hormone (GnRH) analogues in women with recurrent endometrial cancer. DESIGN: An open phase II observational trial of GnRH analogues. Serial measurements of gonadotrophins, sex hormones and tumour dimensions were made together with repeat biopsy when possible to assess the response to treatment. SETTING: The outpatient clinics of the Department of Medical Oncology at The Royal London, Royal Marsden and St Bartholomew's hospitals. SUBJECTS: 17 patients with endometrial cancer which had recurred after surgery, radiotherapy and progesterone treatment and was symptomatic, progressive and assessable for response. INTERVENTION: Monthly subcutaneous injection of GnRH analogue. MAIN OUTCOME MEASURES: Reduction in serum gonadotrophins and reduction in tumour dimensions. RESULTS: Six out of 17 patients (35%, 95% CI 12.6-58%) achieved a complete or partial remission which continues for a median of 20 months with no adverse effects. CONCLUSION: GnRH analogues have a significant antitumour effect in recurrent endometrial cancer which warrants further examination in comparison with progestogens. PMID- 1751437 TI - Postpartum eclampsia and acute renal failure; treatment with prostacyclin. Case report. PMID- 1751438 TI - Repeated measurement of maternal weight during pregnancy. Is this a useful practice? Patterns of maternal weight gain in pregnancy. PMID- 1751439 TI - Comparison of the T/QRS ratio of the fetal electrocardiogram and the fetal heart rate during labour and the relation of these variables to condition at delivery. PMID- 1751440 TI - A randomized controlled trial of early amniotomy. PMID- 1751441 TI - What is birth asphyxia? PMID- 1751442 TI - Doppler flow velocity waveform analysis in high risk pregnancies: a randomized controlled trial. AB - OBJECTIVE: To test whether the introduction of Doppler waveform analysis into the ultrasound department of a tertiary level hospital reduces neonatal morbidity and improves obstetric management. DESIGN: A randomized controlled trial. SETTING: Department of Ultrasound, King Edward Memorial Hospital, Perth, Western Australia. SUBJECTS: 505 women with pregnancy abnormalities referred to an ultrasound department for fetal investigation during the third trimester. INTERVENTION: Continuous wave Doppler studies of umbilical and uteroplacental arterial circulations. Results were revealed to patients and clinicians. MAIN OUTCOME MEASURES: Principal end point was the duration of neonatal stay in hospital; other end points included the number and type of fetal heart rate monitoring studies, obstetric interventions, frequency of fetal distress, birthweight, Apgar scores and need for neonatal intensive care. RESULTS: There was no effect on the duration of neonatal stay in hospital. Small trends in obstetric management were observed with study group patients having fewer contraction stress tests, less likelihood of antepartum fetal distress, and more likelihood of fetal distress after induction of labour leading to emergency caesarean section. Depressed Apgar scores were more frequent in the study group. CONCLUSION: Introduction of Doppler waveform studies did not result in reduced neonatal morbidity but did have a small effect on obstetric management. For each institution the role of Doppler studies in late pregnancy will be influenced by the usage of other tests of fetal welfare already entrenched in clinical practice. PMID- 1751443 TI - Trophoblast deportation in pre-eclamptic pregnancy. AB - OBJECTIVES: To examine the deportation of trophoblast cells into the maternal blood in pre-eclamptic (gestational proteinuric hypertension) and normal pregnancy. DESIGN: The monoclonal anti-cytokeratin antibody JMB2 was used in the APAAP technique to label trophoblast cells in cell smears of uterine vein blood obtained at caesarean section. SUBJECTS: 10 women with proteinuric pre-eclampsia requiring caesarean section, 10 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia and five control women who had never been pregnant. RESULTS: Three populations of trophoblast cells were identified; two mononuclear cytotrophoblast types with diameters varying from 11-14 microns and 19-25 microns respectively, and multinucleated syncytiotrophoblast cells varying in size from 23-88 microns. Women with pre-eclampsia had more trophoblast cells in uterine vein blood than were found in pregnant women without pre eclampsia. There was no correlation between the numbers of trophoblast cells and the stage of gestation or severity of the pre-eclampsia, although an acute maternal or fetal event necessitating delivery was associated with increased deportation of trophoblast. Mononuclear cytotrophoblast cells were detected in the peripheral blood of only 1 of 5 pre-eclamptic patients, despite their presence in the uterine vein blood of all 5 women. CONCLUSIONS: Trophoblast deportation is increased in pre-eclamptic pregnancy, with both cytotrophoblast and syncytiotrophoblast present in the uterine vein blood, but there is no correlation with the severity of the disease. In some cases cytotrophoblast may also enter the peripheral circulation. PMID- 1751444 TI - (Patho)physiological implications of chronic dietary sodium restriction during pregnancy; a longitudinal prospective randomized study. AB - OBJECTIVE: To study the possible pathophysiological implications of long continued dietary sodium restriction in pregnancy. DESIGN: Longitudinal prospective randomized study of the effects of a low sodium diet compared with unrestricted sodium intake in pregnancy. SETTING: Academic Department of Obstetrics and Gynaecology at Sint Radboud Hospital, Nijmegen, The Netherlands. SUBJECTS: 42 healthy nulliparous women. INTERVENTION: A low sodium diet (20 mmol sodium daily) started in the 14th week of pregnancy and stopped after delivery. MAIN OUTCOME MEASURES: Maternal weight gain, food intake, blood pressure, cardiac output, systemic vascular resistance, haematocrit and birthweight. RESULTS: Total maternal weight gain and dietary energy intake during pregnancy and weight at 1 and 6 weeks postpartum were significantly lower in the low sodium group. Blood pressure during pregnancy did not show major differences. Stroke volume and cardiac output during pregnancy were significantly lower in the low sodium group whereas systemic vascular resistance was significantly higher. Haematocrit values in the low sodium group tended to be lower during pregnancy, but were significantly lower at 1 and 6 weeks postpartum than in the unrestricted group. Placental and birthweights were not significantly different between the two groups. CONCLUSIONS: Chronic dietary sodium restriction during pregnancy is characterized by a diminished body fat accumulation and a reduction in circulating volume, due to a decrease in both plasma and red cell volume, in combination with a high systemic vascular resistance without major effects on blood pressure and birthweight. PMID- 1751445 TI - Bilateral oophorectomy and hysterectomy in the treatment of intractable pelvic pain associated with pelvic congestion. AB - OBJECTIVE: To determine whether bilateral oophorectomy combined with hysterectomy is an effective treatment for chronic pelvic pain due to congestion. DESIGN: Prospective non-randomized single centre study. SETTING: Tertiary referral centre to a specialist pelvic pain clinic in a teaching hospital. SUBJECTS: 36 women, 33 of whom had failed to obtain long term relief of pain on medical therapy. MAIN OUTCOME MEASURES: Relief of pain, coital frequency, and effect on daily life. Histology of uterus and ovaries. RESULTS: Median pain score on visual analogue scale fell from a pre-operative value of 10 to 0 at one year. Twelve of the 36 women had some residual pain at one year postoperatively, but in only one woman was the pain affecting her daily life. Thirty women were noted to have pelvic tenderness pre-operatively, at one year, 26 had no tenderness and four minimal tenderness on pelvic examination. The median frequency of sexual intercourse increased from once per month preoperatively to eight times per month one year postoperatively. The uterus was histologically normal in 25 women, adenomyosis was present in eight of whom two had ovarian endometriosis. Fibroids were present in three and endometriosis was found confined to the ovaries in one woman. Multiple peripheral cysts were present in the ovaries of 25 women. CONCLUSION: Bilateral oophorectomy combined with hysterectomy and hormone replacement therapy is an effective treatment for chronic pelvic pain due to venous congestion, which has failed to respond to medical treatment and leads to restoration of normal coital function and daily life. PMID- 1751446 TI - Cancer of the cervix in women under 40 years of age, a regional survey, 1975 1984. AB - OBJECTIVE: To review the method and results of treatment of carcinoma of the cervix in women less than 40 years old. DESIGN: Retrospective review of all available case records. SETTING: Yorkshire Regional Health Authority. SUBJECTS: 428 women less than 40 years old treated for stage IB-IV carcinoma of the cervix between 1975 and 1984 inclusive. MAIN OUTCOME MEASURES: Overall survival by stage, effect of age, identifiable factors of prognostic significance, survival, grade 3 morbidity and pattern of recurrence in relation to treatment. RESULTS: The 5-year actuarial percentage survival by stage was 78.4 (IB), 54.4 (II), 18.4 (III) and 0 (IV). Identifiable factors of prognostic importance were stage, nodal metastases (P less than 0.001) and tumour grade (P less than 0.01). CONCLUSION: Primary surgical treatment for young women with early disease allows ovarian conservation and the avoidance of radiotherapy in 80% of them. Such treatment results in less local recurrence, particularly evident in patients with moderate or poorly differentiated tumours and a lower incidence of serious morbidity. PMID- 1751447 TI - Going public. PMID- 1751448 TI - Heat shock and thermotolerance in plant and animal embryogenesis. AB - Although the strategies of early embryogenesis differ greatly among multicellular eukaryotes, there are certain parallels in structure, form, and function that cross even kingdom lines: the extreme heat sensitivity of zygotes and very early embryos, followed by the acquisition of thermotolerance during subsequent development, is one such parallel. The heat sensitivity may be so extreme that even moderate increases in temperature result in lethality (generally associated with the earliest phases of embryogenesis), or the effects may be less severe, resulting in defects in development but not in lethality. Mechanistically, and molecularly, these two forms of thermosensitivity appear to have different origins. On the one hand, outright lethality appears to result from an inability to induce heat shock genes and proteins; on the other hand, heat-induced developmental defects appear to result from an alteration in expression of non heat shock genes and from a delay in the overall developmental program that generally accompanies the cell's response to heat shock. This review is focused on the developmental regulation of the heat shock response during early embryogenesis and on the impact of this regulation on the development of both animal and plant embryos. The two basic issues that we address here are (i) the expression of heat shock genes in the absence of heat shock during embryogenesis and (ii) the expression (or lack of expression) of heat shock genes after deliberate exposure of the embryos to heat shock and the consequences of this expression on its subsequent survival and development. PMID- 1751449 TI - Multiple regions of v-Fos protein involved in the activation of AP1-dependent transcription: is trans-activation crucial for transformation? AB - We show that trans-activation by v-Fos requires several functionally separable regions, including the leucine repeat, the basic DNA-binding region, a directly adjacent acidic cluster, and additional flanking sequences. Structural alterations in the flanking regions are in part responsible for the greater trans activating potential of the fos gene product of the Finkel-Biskis-Reilly mouse osteosarcoma virus, FBR-MuSV. A point mutation in the acidic cluster, which is known to activate the immortalizing potential of Fos, leads to a significant increase in trans-activation. However, comparison of the trans-activating and transforming properties of mutant Fos proteins suggests that functions other than trans-activation are involved in the induction of transformation. PMID- 1751450 TI - Soluble HTLV-I Tax1 protein stimulates proliferation of human peripheral blood lymphocytes. AB - Human T-cell leukemia virus type I (HTLV-I) is associated with two human diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). Lymphocytes from patients with ATL or TSP/HAM display abnormal proliferation properties in culture. Here we report that purified, soluble Tax1 protein can be taken up by, and stimulate proliferation of, uninfected human peripheral blood lymphocytes (PBLs) that have been stimulated with phytohemagglutinin (PHA). Tax1 was 40 to 70% as active as interleukin-2 (IL-2) in stimulating proliferation of PBLs. Heat inactivation, chloroform extraction, and immunoprecipitation with antisera specific for Tax1 each abolished the ability of the protein to stimulate lymphocyte proliferation. Tax1 failed to stimulate PBL proliferation in the absence of PHA. After an initial round of cell division, Tax1-treated PBLs exhibited prolonged sensitivity to IL-2-induced proliferation. These results indicate that Tax1 can stimulate lymphocyte proliferation in culture and imply that extracellular Tax1 may be involved in the spontaneous proliferation of TSP/HAM lymphocytes and the IL-2 dependent proliferation of ATL lymphocytes. PMID- 1751451 TI - A cluster of genes that affects nucleoid segregation in Salmonella typhimurium. AB - Thirteen conditional lethal mutations in genes of Salmonella typhimurium map at the clmF locus and affect both viability and the faithful partitioning of daughter nucleoids. These mutations have now been divided into three complementation groups by using cloned fragments of S. typhimurium DNA and renamed parC, parE, and parF. The proteins produced from the cloned fragments predict that ParC is an 85-kD protein, ParE is 75 kD in size, and ParF, 27 kD. The parE gene is about 5 kb upstream of the parC gene, and parC is just upstream of parF. Genes situated between parC and parE produce at least two proteins of unknown function. The DNA sequence of the S. typhimurium parC gene was determined and has 56% homology with the first 1400 base pairs of the Escherichia coli gryA gene, which encodes the A subunit of DNA gyrase, and 85% homology with the E. coli parC gene. Despite the strong homology between gryA and parC, these two genes cannot substitute for one another. The DNA sequence of the S. typhimurium parF gene was determined and predicts a protein with a hydrophobic N terminus. The ParF protein may interact with ParC and ParE to anchor these proteins to the membrane. These results raise questions about the relative roles of gyrase and ParCEF in nucleoid decatenation. In addition, the parC and gyrA genes provide an example of the evolution of essential functions by gene duplication. PMID- 1751452 TI - Selective elimination of recombinant genes in vivo with a suicide retroviral vector. AB - The ability to express recombinant genes in vivo offers potential new treatments for human disease if questions of safety and toxicity can be addressed. Complications of gene transfer could include, for example, overexpression of introduced genes for growth or angiogenic factors or insertional mutagenesis, both of which could cause uncontrolled cell growth. We report the development of a suicide retroviral vector that provides a method to eliminate cells undergoing rapid growth in vivo. A murine amphotropic retroviral vector was constructed in which the gene for herpesvirus thymidine kinase was included to render proliferating cells sensitive to ganciclovir, and the Escherichia coli beta galactosidase gene served as a reporter. This vector's efficacy was first assessed in vitro, and beta-galactosidase activity was abolished in several cell lines after treatment with ganciclovir. In vivo, a transplantable murine CT26 adenocarcinoma whose cells were transduced with this vector regressed completely after administration of ganciclovir. In contrast, expression in nondividing cells within rabbit arteries transduced by retroviral infection in vivo was unaffected. This suicide vector therefore eliminates transformed cells but allows survival of normal nondividing cells that express its specific recombinant genes in vivo, and may thus improve the safety and efficacy of gene transfer into living organisms. PMID- 1751453 TI - Generation of synaptic noise: selective involvement of neuronal subsets. AB - All central neurons are subjected to continuous and random variations of their membrane potential because of "spontaneous" activity in their presynaptic afferents. This activity, which is called synaptic noise, is presumed to be responsible for the uncertainty of the input-output relation in these cells. In the Mauthner cell of teleosts, noise is mainly inhibitory, and is generated by the release of neurotransmitter in a probabilistic manner. This inhibitory activity has been studied in detail previously. Taking advantage of this understanding, we have constructed a model of the inhibitory networks and their target in order to determine the conditions required to reproduce the main stochastic aspects of synaptic noise. We have used a combination of computer simulations and simple semianalytical arguments. We conclude that, surprisingly, cells in the presynaptic networks do not contribute equally to these background fluctuations. Rather, noise is generated primarily by the operation of subsets of afferent cells: the spectrum is either dominated by signals originating from interneurons which make few terminals on the Mauthner cell, or by the output of "burster" cells firing spike trains rather than single spikes. Both possibilities lead to specific predictions, one of which has already been verified. PMID- 1751454 TI - Molecular biology and the new paradigm. PMID- 1751455 TI - Pressure and posture. PMID- 1751456 TI - Randomised double-blind trial of bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration. AB - The results of a randomised double-blind clinical trial of 0.1% bromovinyldeoxyuridine (BVDU) and 1% trifluorothymidine (TFT) in 60 patients with corneal dendritic ulceration are presented. There was no significant difference between BVDU and TFT in terms of numbers of ulcers healed (p = 0.61), mean healing time (p = 0.065), and cumulative healing rate (p = 0.058). No serious side effects were observed, though transient stinging was recorded in five patients receiving TFT and in three patients receiving BVDU. One patient in the group treated with TFT developed a punctate epitheliopathy. PMID- 1751457 TI - Postural change of intraocular and blood pressures in ocular hypertension and low tension glaucoma. AB - The effect of body position on the intraocular and blood pressures of normal volunteers and of patients with ocular hypertension and low tension glaucoma was studied. Changing from the sitting to the supine position increased the intraocular pressure by an average of 4.4 (SD 2.0) mm Hg in the control group, 4.0 (SD 2.0) mm Hg in the ocular hypertension group, and 4.1 (SD 1.8 mm Hg) in the low-tension glaucoma group. After 30 minutes in the supine position the intraocular pressure in normal volunteers and patients with low tension glaucoma remained stable. In contrast patients with ocular hypertension showed a further significant increase in intraocular pressure of 1.6 (SD 2.8) mm Hg (p = 0.004). This was accompanied by an equally significant decrease in blood pressure (p less than 0.001). We believe that these are manifestations of different mechanism of intraocular pressure regulation between these groups. PMID- 1751458 TI - Plasma viscosity or erythrocyte sedimentation rate in the diagnosis of giant cell arteritis? AB - Plasma viscosity (PV) has replaced the erythrocyte sedimentation rate (ESR) as a routine laboratory test in many hospitals. The finding of a normal PV but raised ESR in a case of biopsy proved giant cell arteritis (GCA) cast doubt on this substitution in cases of suspected GCA. To assess the equivalence of PV and ESR in the diagnosis of this disease 40 suspected cases were prospectively investigated with both tests. The correlation between the two tests was good (r = 0.742, p less than 0.0001). The substitution of one test for the other would appear to be justified in most cases of suspected GCA. In the presence of biopsy proved disease, however, the PV and ESR each produced 13.3% false negatives. These occurred both in combination with and independently of the other test showing that, when in error, the two tests may not be equivalent. In cases of doubt the performing of both PV and ESR tests together improves but does not achieve complete diagnostic accuracy. Clinical judgment based on careful assessment of all available symptoms and signs must remain the foundation of diagnosis. PMID- 1751459 TI - Postoperative conjunctival chemosis in cataract surgery caused by subconjunctival gentamicin injection. AB - A prospective study of 75 patients undergoing cataract surgery was conducted to identify the cause of postoperative conjunctival chemosis seen in patients with cataracts in this department. The patients were split in three groups of 25 each. Group G patients were given a subconjunctival injection of gentamicin at the end of the cataract procedure; group W patients did not receive subconjunctival gentamicin, but a cellulose wick drain was used during the procedure; and Group GW patients received a subconjunctival injection of gentamicin and a wick drain was also used. The incidence, severity, and the duration of chemosis were observed in the three groups. Chemosis was seen only in groups G and GW, and the difference between the number of patients who received gentamicin and those who did not receive gentamicin was significant (p less than 0.001). PMID- 1751460 TI - Should nylon corneal sutures be routinely removed? AB - Three groups of patients who had undergone cataract extraction through a corneal incision closed with 10/0 nylon sutures one, two, and three years previously were recalled to determine the incidence of suture related complications. Broken corneal sutures were found in 87.5% of patients after two years and 90% after three years and were causing symptoms in over half the patients. It is recommended that 10/0 nylon corneal sutures be routinely removed no later than one year after surgery. PMID- 1751461 TI - Optic foraminal radiography--a redundant investigation? AB - A retrospective study of all plain radiographs taken of optic foramina during the six years 1984-9 inclusive, comprising a total of 318 examinations, was carried out in order to determine the role of this investigation in patients with ophthalmic disorders. All but one of the radiographs were reported as showing no abnormality. However, for this exception, review of the radiographs showed that the optic foramina were asymmetrical but fell within the normal range. This study indicates that plain radiographs of the optic foramina have little or no useful function. Abandoning the use of these views as a routine will result both in a reduction in radiation hazard and in considerable financial saving. PMID- 1751462 TI - Prosthesis motility with and without intraorbital implants in the anophthalmic socket. AB - Ocular prosthesis motility was measured and compared in 15 patients with a primary baseball implant after enucleation of an eye, in 11 patients with a secondary baseball implant, in 12 patients with an Allen implant, and in 11 patients without any intraorbital implant. In all patients a noticeable lag of movement of the prosthetic eye was measured: in the extreme directions of gaze the excursions of the prosthesis were far less in comparison with the contralateral normal eye. For normal eye movement round the primary position of gaze, however, the prosthesis motility in the primary baseball and Allen implant group appeared to be sufficient to give a lifelike appearance. The average motility of the prostheses in these two groups did not differ. The motility in the secondary baseball group and in the group without an implant was evidently worse. In the last group the prosthesis motility was most impaired. We conclude that the insertion of an implant, even when inserted some time after the enucleation (a secondary implant), improves the motility of the prosthesis markedly. We recommend the primary baseball implant as the correction of choice after enucleation. PMID- 1751463 TI - Postinflammatory cataracts in the mouse: induction by human mycoplasma-like organisms. AB - Cataracts often occur in humans secondary to uveitis. Uveitis may be caused by various infectious agents, but rarely is the agent detected in the cataract. Mycoplasma-like organisms (MLO) were recently reported to cause human uveitis and retinitis. Cataracts were often present in those inflamed eyes. MLO are intracellular cell wall deficient pathogenic bacteria. They are pleomorphic tubulospherical and filamentous organisms with a characteristic ultrastructural appearance. No MLO culture system has been found despite 20 years of effort. The diagnosis of MLO disease rests on detection of the organisms in parasitised cells by a transmission electron microscope and response to antibiotics. In human intraocular inflammatory disease MLO are detectable in parasitised leucocytes and retinal pigment epithelial cells at the disease sites. Inoculation of MLO from a human source into mouse eyelids produced intraocular, chronic, progressive, inflammatory disease, with intraocular leucocytes parasitised by MLO in 15 of 100 mice versus 0 in 200 controls (p less than 0.05). This report describes the cataracts with MLO-parasitised intralenticular leucocytes in the inflamed eyes of 14 of those 15 mice versus 0 in 200 control mice (p less than 0.05). The results indicate that MLO penetrated the lens capsules to produce the cataracts, and they suggest that MLO could cause human cataracts. Alternative methods for detection of MLO and rifampin treatment of MLO intraocular disease are discussed. PMID- 1751464 TI - Ofloxacin compared with chloramphenicol in the management of external ocular infection. AB - The safety and efficacy of 0.3% ofloxacin in treating bacterial ocular infections was compared with that of 0.5% chloramphenicol in a parallel-group, randomised clinical trial at five sites. Clinical and microbiological improvement rates were studied in 84 culture-positive patients. Patients with suspected bacterial ocular infections were evaluated for clinical improvement and were included in drug safety and comfort analyses. Clinical improvement did not differ significantly between drug treatments. All patients completing the study (79 assigned ofloxacin, and 74 chloramphenicol) showed clinical improvement. Clinical improvement in the culture-positive groups was 100% (41/41) after ofloxacin treatment, and 95% (41/43) after chloramphenicol treatment. Microbiological improvement rates were similar for the two drugs: 85% (33/39) improved with ofloxacin, and 88% (38/43) improved with chloramphenicol. Both drugs were well tolerated. Adverse reactions possibly due to the study medication occurred in 1% (1/89) of those who received ofloxacin, and in 4% (4/93) of those who received chloramphenicol. PMID- 1751465 TI - Orbital xanthogranuloma in adults. AB - The onset of periorbital xanthogranuloma in adults is rare and may be accompanied by haematological abnormalities and malignancy. The appearance of the eyelid lesions is virtually diagnostic, producing readily recognisable diffuse, yellow plaques, and affected patients should be investigated and reviewed regularly for systemic disease. Three cases are described, in which periorbital cutaneous plaques were associated with abnormal tissues in the superior part of the orbit; these abnormal tissues caused displacement or restricted movement of the globe or upper eyelid. The possibility that two cases represent a necrobiotic type of xanthogranuloma is presented. Nine years after the onset of xanthogranuloma one patient developed non-Hodgkin's lymphoma. A multiple-drug regimen of systemic chemotherapy, given for lymphoma, caused a marked clinical reduction in the periorbital xanthogranuloma. PMID- 1751467 TI - Inadvertent application of silicone foam elastomer catalyst to the eye. AB - Silicone foam elastomer is used extensively to treat granulating wounds. A case is presented in which the catalyst to the polymer was inadvertently applied to the eye. This produced conjunctival and corneal injury, which was slow to heal and resistant to conventional treatment. This form of injury has not previously been described. PMID- 1751466 TI - Choroidal involvement in lymphomatoid granulomatosis. AB - A 13-year-old boy with evidence of pulmonary lymphomatoid granulomatosis developed monocular diplopia. Fluorescein angiography revealed bilateral choroidal involvement. Following treatment with vincristine, cyclophosphamide, and prednisone his diplopia resolved and the angiographic appearances returned to normal. PMID- 1751468 TI - Cleft anterior segment with maternal hypervitaminosis A. AB - We report a case of an 'hourglass' cornea and iris with reduplicated lens in the left eye of an infant girl. An excess of vitamin A products had been taken by the mother during pregnancy. Mechanisms by which vitamin A excess could have caused this are discussed. PMID- 1751469 TI - Acquired pigmentation simulating Peutz-Jeghers syndrome: initial manifestation of diffuse uveal melanocytic proliferation. AB - A 74-year-old man with an occult carcinoma of the colon developed pigmentation of the mouth and penis typical of the Peutz-Jeghers syndrome as the first manifestation of bilateral diffuse uveal melanocytic proliferation. The simultaneous appearance of extraocular pigmented lesion and those in the uveal tract of both eyes of this patient provides further evidence that bilateral diffuse uveal melanocytic proliferation may be caused by activation of occult melanocytic naevus cells in response to either a hormone-producing carcinoma or to some other common oncogenic stimulus. PMID- 1751470 TI - Ocular myositis as first presenting symptom of human immunodeficiency virus (HIV 1) infection and its response to high-dose cortisone treatment. AB - A 30-year-old male presented with signs of ocular inflammation and motility disturbances in an early stage of HIV infection. The provisional diagnosis of an ocular myositis was confirmed by orbital echograms. A general check up revealed positive anti-smooth-muscle antibodies and antinuclear antibodies as well as a raised erythrocyte sedimentation rate. Oral steroid treatment in addition to steroid eyedrops achieved complete resolution of clinical and sonographic symptoms within 15 weeks. Autoimmune phenomena are well known presentations of HIV infection. In this case oral cortisone proved to be an effective therapy even in the setting of an HIV infection. PMID- 1751471 TI - Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides. AB - We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions. PMID- 1751472 TI - Oestrus ovis ophthalmomyiasis acquired in the UK: case report and scanning electron microscopic study. AB - A case of external ophthalmomyiasis acquired in the UK is reported. Oestrus ovis infestation of the external conjunctiva is described and a scanning electron microscopic study made of the first stage larvae. To our knowledge this represents only the third case reported of UK acquisition of ophthalmomyiasis. PMID- 1751473 TI - Herpes simplex keratitis in renal transplant patients. PMID- 1751474 TI - Fixed breathing frequency decreases end-tidal PCO2 in humans. AB - We tested the effect of a fixed breathing frequency on the partial pressure of CO2 in the end-tidal air (PETCO2) in resting healthy subjects. In the first experiment, three different rates of breathing were dictated: the same frequency of breathing as the subject's control one (1f), a double frequency (2f), and half of the control frequency (0.5f). 10 min dictate of 1f and 2f induced a decrease of PETCO2. The dictate of 0.5f had no significant effect on PETCO2. In the second experiment, 1f was dictated for 30 min, inducing a decrease of PETCO2 throughout the duration of the dictate. These results demonstrate that fixing the breathing frequency by the dictate affects the chemostatic control of ventilation. PMID- 1751475 TI - Cellular sodium and calcium in experimental hypertension. PMID- 1751476 TI - Interaction of the neuromuscular blocking drug atracurium with muscarinic acetylcholine receptors. AB - On isolated rat heart atria, atracurium competitively antagonized the negative chronotropic effect of methylfurmethide, shifting the concentration-response curve to the right without diminishing the agonist's maximal effect; Kd calculated from dose ratios was 3.0 mumol/l. On the longitudinal muscle of rat ileum, atracurium antagonized the effect of methylfurmethide in a non-competitive manner; at 50 mumol/l atracurium, the maximum response to methylfurmethide was diminished by about 50%. Atracurium antagonized the binding of (3H)quinuclidinyl benzilate [3H)QNB) to muscarinic binding sites in the atria, ileal longitudinal muscle and cerebellum with IC50 values of 5-8 mumol/l, and in brain cortex of 25 mumol/l. Atracurium was little efficient, however, in antagonizing the binding of N-(3H-methyl) scopolamine [3H)NMS) to muscarinic binding sites. Complete blockade was not achieved at concentrations up to 1 mmol/l. Concentrations required to diminish the binding by 50% were 10 - 1000 times higher for (3H)NMS than for (3H)QNB. Atracurium brought about the dissociation of (3H)QNB-receptor complexes, but its effect was considerably stronger at a concentration of 30 mumol/l than at 1 mmol/l. Atracurium slowed down the dissociation of (3H)QNB-receptor complexes observed after the addition of atropine. The effects of atracurium on the dissociation of (3H)NMS-receptor complexes were similar to those on (3H)QNB receptor complexes, but a high concentration of atracurium (1 mmol/l) produced a transient increase in (3H)NMS binding preceding its subsequent dissociation. Although the observations of the antagonism by atracurium of the effect of methylfurmethide on the heart atria, and of the inhibition of the specific binding of (3H)QNB to the atria, ileal smooth muscle, cerebellum and brain cortex are compatible with the assumption of a competitive interaction, the discrepancy between the effects of atracurium on the binding of (3H)QNB and (3H)NMS indicates that atracurium does not bind to the same binding site as (3H)QNB and (3H)NMS. It appears that most effects of atracurium on muscarinic receptors are allosteric and that both negative and positive cooperatives play a role in interactions between atracurium and muscarinic ligands. PMID- 1751477 TI - Influence of light regimen and the time of year on circadian oscillations of thyroid hormones in rats. AB - Male SPF rats (Wistar strain) were adapted in the course of the year to natural light (N) and to a 12:12 h (light:dark) artificial light (A) regimen. At approximately the spring and autumn equinox and the summer and winter solstice, rats were killed at 3-h intervals over a 24 h period and their serum thyroxine (T4), triiodothyronine (T3) and reverse T3 levels were determined. The light regimen and time of year significantly influenced the basic characteristics of the oscillations of the hormones. In the N regimen, T4 levels (T3 levels less) culminated in all seasons in correlation to sunrise. In the A regimen they culminated irregularly after daybreak. In animals with the N regimen, the oscillations of the hormones were rhythmic in all seasons, but in the A regimen in only some seasons. In the N regimen, the mean daily T4 concentration value (the mesor) was the highest in the spring and the lowest in the autumn; in the A regimen the mesors were the same, except for a low mesor in the autumn. In both light regimens, the T3 mesors were the highest in the autumn and low in the winter; the rT3 mesors were a mirror image of the T3 mesors. The annual mean of serum T4 concentrations was lower in the N group than in the A group. PMID- 1751478 TI - Observations on the biological activity of epitestosterone. AB - Epitestosterone, a 17 alpha-epimer of testosterone is a normal constituent of body fluids in many species including man. It has long been believed that it is devoid of any biological significance. However, it is now demonstrated that in in vivo experiments on castrated male mice it counteracts the action of testosterone on androgen-dependent organs. In vitro experiments show that on the overall antiandrogenicity of epitestosterone participate true antiandrogenic action due to the binding to androgen receptors, strong 5 alpha-reductase inhibiting activity as well as a weak antigonadotropic activity. Epitestosterone is devoid of any embryotoxicity as checked by chick embryo-toxicity screening test. PMID- 1751479 TI - Effect of oyster fungus (Pleurotus ostreatus) on serum and liver lipids of Syrian hamsters with a chronic alcohol intake. AB - The authors studied the effect of oyster fungus (Pleurotus ostreatus) (2% dried fruiting bodies in a standard diet) on the serum and liver lipids of growing male Syrian hamsters with a chronic alcohol intake (a 15% aqueous solution). After eight weeks' alcohol intake there was an increase in their serum cholesterol, triacylglycerol (TG) and phospholipid (PL) concentration, 40 - 60% of which was accounted for by an increase in the very low density lipoprotein (VLDL) concentration. The proportion of VLDL in the lipoprotein pool rose by almost 15%, whereas the proportion of high density lipoproteins (HDL) fell. The simultaneous administration of the fungus in the diet reduced the cholesterol level below the value in the control animals not given any alcohol. Both the serum TG and the VLDL concentration fell by 30%, but neither the chemical composition and concentration of the HDL nor the cholesterol concentration were affected. The addition of the fungus to the diet completely abolished the increase induced in the liver cholesterol and TG concentration by the chronic intake of alcohol. PMID- 1751480 TI - Influence of hypergravity on the pH profile and proteolytic activity of the avian gastrointestinal tract. AB - The present study deals with the effect of hypergravity (2xg) on the pH and on the proteolytic activity in the digesta of the gastrointestinal tract of Japanese quails during intense growth. The birds were raised on a semisynthetic diet containing free amino acids (A) and a commercial diet (B). During days 35 till 40 post-hatching the quails were exposed to hypergravity (2xg) using a specially designed centrifuge. On days 40 (experimental group, 2xg) and 41 (control group, 1xg) the animals were sacrificed. The pH of the digesta in various segments of the gastrointestinal tract was measured by means of a semi-microelectrode. Total proteolytic activity was determined by means of azo-dye-modified proteins serving as general proteolytic substrates. Hypergravity leads in general to an alkalization of digesta in various parts of the gastrointestinal tract. In case of the gizzard and duodenum (diet A) and also in the distal jejunum (diet B) the differences are significant. With both diets, hypergravity leads to a considerable decrease in the total proteolytic activity. The reduction is most expressed in the duodenum and jejunum. Changes in the pH of digesta compensate for the decrease in the proteolytic activity. This may explain why hypergravity per se does not seem to impair growth of the Japanese quails. PMID- 1751481 TI - P-aminohippurate accumulation in kidney cortex slices: stimulation by dicarboxylates, amino acids and their oxoanalogues. AB - The effect of various amino acids and oxoacids on the accumulation of PAH in rat kidney cortex slices was determined. The following compounds were found to increase the PAH tissue to medium ratio (T/MPAH): a) dicarboxylic acids: glutarate, 2-oxoglutarate and oxaloacetate, b) amino acids: glutamate, isoleucine, leucine, valine, methionine, tryptophane, histidine, threonine and glycine, c) monocarboxylates: hydroxymethionine, oxovaline, oxoisoleucine and oxoleucine. There were no marked concentration/effect differences to glycine, glutamate, glutarate and oxovaline. Ouabain inhibited T/MPAH only slightly, but abolished its increase by pyruvate, 2-oxoglutarate and histidine. Oxygen hyposaturation abolished the T/MPAH increase caused by 2-oxoglutarate, pyruvate, glutamate and histidine. It is concluded that various substrates stimulating the organic anion transport system (OATS) do so namely by improving the energy supply, although the direct participation of dicarboxylates in OATS could be of relevance namely in short-lasting variations. PMID- 1751482 TI - Observations on respiratory and cardiovascular rhythmicities during yogic high frequency respiration. AB - Yogic high-frequency respiration--kapalabhati (KB)--was studied in 24 subjects from a point of rhythmicity. Respiratory movements, blood pressure and R-R intervals of ECG were recorded in parallel and evaluated by spectral analysis of time series. Respiratory signals during KB were modulated by 0.1 Hz rhythm in 82% of experiments. This component was also present in R-R intervals and blood pressure during KB. Frequency (0.2-0.3 Hz) was observed in 67% of respiratory records. The presence of the component 0.2-0.3 Hz in respiration was dependent on resting respiratory frequency. This frequency component was reduced in R-R intervals but increased in blood pressure during kapalabhati as compared to that at rest. The occurrence of both frequency components in respiration during KB supports the hypothesis about the integrative role of cardiovascular and respiratory rhythms in physiological states characterized by altered respiratory frequency. PMID- 1751483 TI - Effect of indomethacin on selected immune parameters in different age groups of mice. AB - The authors studied the effect of indomethacin on the phagocytic activity of polymorphonuclear leucocytes (PMNL) and on haemolytic antibody formation (plaques) by lymphoid cells of the spleen in 3-, 6- and 12-month-old mice. In 3- and 12-month-old animals the phagocytic activity of the PMNL was significantly inhibited. Plaque formation was likewise significantly inhibited in 3-month-old mice, but it was significantly raised in 6- and 12-month-old animals. PMID- 1751484 TI - Reconstitution of a heat shock effect in vitro: influence of GroE on the thermal aggregation of alpha-glucosidase from yeast. AB - alpha-Glucosidase from yeast is inactivated rapidly at temperatures above 42 degrees C. The thermal inactivation is accompanied by aggregation. The molecular chaperone GroEL suppresses the formation of aggregates by binding the thermally inactivated alpha-glucosidase. Spectroscopic studies suggest that GroEL binds alpha-glucosidase in an intermediately folded state. The complex between alpha glucosidase and GroEL can be dissolved by MgATP. GroES accelerates the MgATP dependent dissociation of the alpha-glucosidase-GroEL complex. At elevated temperatures this release leads to the formation of aggregates, while at lower temperatures native, enzymatically active molecules are formed. PMID- 1751485 TI - 1H NMR studies of DNA recognition by the glucocorticoid receptor: complex of the DNA binding domain with a half-site response element. AB - The complex of the rat glucocorticoid receptor (GR) DNA binding domain (DBD) and half-site sequence of the consensus glucocorticoid response element (GRE) has been studied by two-dimensional 1H NMR spectroscopy. The DNA fragment is a 10 base-pair oligonucleotide, 5'd(GCTGTTCTGC)3'.5'd-(GCAGAACAGC)3', containing the stronger binding GRE half-site hexamer, with GC base pairs at each end. The 93 residue GR-DBD contains an 86-residue segment corresponding to residues 440-525 of the rat GR. Eleven NOE cross peaks between the protein and DNA have been identified, and changes in the chemical shift of the DNA protons upon complex formation have been analyzed. Using these protein-DNA contact points, it can be concluded that (i) the "recognition helix" formed by residues C460-E469 lies in the major groove of the DNA; (ii) the GR-DBD is oriented on the GRE half-site such that residues A477-D481, forming the so-called D-loop, are available for protein-protein interaction in the GR-DBD dimer on the intact consensus GRE; and (iii) the 5-methyl of the second thymine in the half-site and valine 462 interact, confirming indirect evidence [Truss et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7180-7184; Mader et al. (1989) Nature 338, 271-274] that both play an important role in GR-DBD DNA binding. These findings are consistent with the model proposed by Hard et al. [(1990) Science 249, 157-160] and the X-ray crystallographic complex structure determined by Luisi et al. [(1991) Nature 352, 497-505]. PMID- 1751486 TI - Calorimetric studies of the binding of ferric ions to ovotransferrin and interactions between binding sites. AB - Transferrins are two-domain proteins with a very strong site for iron binding located in each domain. Using ultrasensitive titration calorimetry, the binding of ferric ion (chelated with a 2-fold molar excess of nitrilotriacetate) to the two sites of ovotransferrin was studied in detail as well as the binding to the single site in the N- and C-terminal half-molecules. In the presence of excess bicarbonate ion, the binding occurs in two kinetic steps. The fast process of contact binding is instantaneous with respect to instrument response time, is strongly exothermic for the N site and less so for the C site, and corresponds to binding of the chelated ferric ion. The slower process of bicarbonate insertion with concomitant release of nitrilotriacetate occurs on a time scale of 2-20 min over the temperature range 7-37 degrees C and is endothermic for the N site and exothermic for the C site, with rates being significantly slower for insertion at the C site. The delta H of binding is strongly temperature-dependent for both sites, arising from a large negative delta Cp of binding which probably indicates removal of hydrophobic groups from contact with water. When bicarbonate ion is absent, only the fast process of contact binding is seen. Each site within a half molecule is qualitatively similar to the same site in intact ovotransferrin, although quantitative differences were detected. It was shown that contact binding to ovotransferrin occurs reversibly with free exchange of Fe+3 between N and C sites, while the attachment to either site becomes essentially irreversible after bicarbonate insertion. The strong preference for the first ferric ion to bind to the N site is shown to be due to its larger contact binding constant and the faster rate of bicarbonate insertion, relative to the C site, and is not due to stronger thermodynamic binding after bicarbonate insertion. True equilibrium is achieved only over much longer periods of time. In another series of experiments, direct binding studies were carried out between the two half molecules under different states of ligation with Fe+3 in the presence of bicarbonate. The results indicate that the two binding sites in ovotransferrin, separated by ca. 40 A, are not independent of one another but communicate as a result of ligand-dependent changes in the heats and free energies of domain domain interactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1751487 TI - Amino acid sequence and location of the disulfide bonds in bovine beta 2 glycoprotein I: the presence of five Sushi domains. AB - beta 2 glycoprotein I is a plasma protein with the ability to bind with various kinds of negatively charged substances. The complete amino acid sequence and the location of all the disulfide bonds of bovine beta 2 glycoprotein I were determined. Bovine beta 2 glycoprotein I consists of 326 amino acid residues with five asparagine-linked carbohydrate chains. Homology with the human protein was calculated to be 83%. Eleven disulfide bonds in bovine beta 2 glycoprotein I constitute four characteristic domains, Sushi domains, and one modified form of a Sushi domain. PMID- 1751488 TI - Reconstitution of catalytically competent human zeta-thrombin by combination of zeta-thrombin residues A1-36 and B1-148 and an Escherichia coli expressed polypeptide corresponding to zeta-thrombin residues B149-259. AB - Human zeta-thrombin, a catalytically competent serine proteinase, arises from a single chymotryptic cleavage at Trp-148 in alpha-thrombin to generate two nonconvalently associated polypeptide segments designated zeta 1-thrombin (the 36 residue A-chain disulfide linked to B-chain residues B1-148) and zeta 2-thrombin (B149-259). We report here the expression of recombinant zeta 2-thrombin in Escherichia coli and the reconstitution of catalytically competent zeta-thrombin by combination of zeta 1-thrombin with recombinant zeta 2-thrombin. A DNA fragment encoding zeta 2-thrombin was cloned into a pATH2 expression vector as a trpE-zeta 2 fusion gene, in which a factor Xa cleavage site was inserted between the trpE and the zeta 2-thrombin gene. High-level expression of this fusion protein was achieved under the control of the E. coli trp promoter. The expressed zeta 2-thrombin was liberated from the fusion protein by factor Xa cleavage, reduced with DTT, and purified to homogeneity by reverse-phase HPLC. Oxidation of the reduced zeta 2-thrombin in the presence of 80 microM CuSO4 and 6 M urea at pH 8.15 yielded material that was indistinguishable on HPLC from zeta 2-thrombin isolated by resolution of human zeta-thrombin. Catalytically active zeta-thrombin was generated by combination of recombinant zeta 2-thrombin with zeta 1-thrombin that was isolated by resolution of human zeta-thrombin. Recombinant zeta-thrombin displayed catalytic activities, toward a small chromogenic substrate and fibrinogen, that were similar to those of alpha-thrombin prepared from human blood plasma and zeta-thrombin obtained by treatment of alpha-thrombin with chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751489 TI - A sectored colony assay for monitoring mutagenesis by specific carcinogen-DNA adducts in Escherichia coli. AB - To study the mutagenicity of various carcinogen-DNA adducts in Escherichia coli, a cassette plasmid was developed that permits positioning of specific carcinogen modified bases within the ATG initiation codon of the lacZ' alpha-complementation gene. Adduct-induced mutations inactivate the gene and lead to formation of blue and white sectored colonies when transformants from an alpha-complementing version of E. coli strain AB1157 are grown on media containing 5-bromo-4-chloro-3 indolyl beta-D-galactoside. In the absence of mutation, blue colonies are produced. This system has been used to measure the mutagenicity of O6-methyl-, O6 ethyl-, and O6-benzyl-2'-deoxyguanosine residues incorporated in place of the normal 2'-deoxyguanosine of the ATG initiation codon. Although a low percentage of sectored colonies was produced in this repair-proficient strain, pretreatment of the bacteria with N-methyl-N'-nitro-N-nitrosoguanidine to disable DNA repair led to a dose-dependent increase in the percentage of sectored colonies. This percentage increased as a function of modified guanine in the order O6-benzyl- less than O6-methyl- less than O6-ethyl-2'-deoxy-guanosine. The only mutations detected at the site of incorporation of these O6-substituted guanines were G-to A transitions. This sectored colony assay system permits convenient screening of large numbers of colonies and simplifies quantification of modified-base-induced mutations whether they be single-base changes, frameshifts, insertions, or deletions. PMID- 1751490 TI - DNA cross-linking and sequence selectivity of aziridinylbenzoquinones: a unique reaction at 5'-GC-3' sequences with 2,5-diaziridinyl-1,4-benzoquinone upon reduction. AB - Several bifunctional alkylating agents of the aziridinylbenzoquinone class have been evaluated as potential antitumor agents. 3,6-Bis[(2-hydroxyethyl)amino]-2,5- diaziridinyl-1,4-benzoquinone (BZQ), 2,5-diaziridinyl-1,4-benzoquinone (DZQ), 3,6 bis(carboxyamino)-2,5-diaziridinyl- 1,4-benzoquinone (AZQ), and six analogues of AZQ have been studied for their ability to induce DNA interstrand cross-linking, as measured by an agarose gel technique, and to determine whether they react with DNA in a sequence-selective manner, as determined by a modified DNA sequencing technique. At an equimolar concentration (10 microM), only DZQ and BZQ showed any detectable cross-linking at pH 7 without reduction. Cross-linking was enhanced in both cases at low pH (4). Reduction by ascorbic acid at both pH's increased the cross-linking, which was particularly striking in the case of DZQ. In contrast, AZQ and its analogues only produced a significant level of cross-linking under both low-pH and reducing conditions, the extent of cross-linking decreasing as the size of the alkyl end group increased. The compounds reacted with all guanine N7 positions in DNA with a sequence selectivity similar to other chemotherapeutic alkylating agents, such as the nitrogen mustards, although some small differences were observed with BZQ. Nonreduced DZQ showed a qualitatively similar pattern of reactivity to the other compounds, but on reduction (at pH 4 or 7) was found to react almost exclusively with 5'-GC-3' sequences, and in particular, at 5'-TGC-3' sites. A model to explain this unique reaction is proposed. PMID- 1751491 TI - Nitrosamine-induced cancer: O4-alkylthymine produces sites of DNA hyperflexibility. AB - The carcinogenic properties of N-nitroso compounds are associated with their ability to alkylate DNA, in particular to form O6-alkylguanine and O4 alkylthymine. DNA duplexes containing either O6-alkylguanine or O4-alkylthymine were synthesized, and each duplex was ligated to form a set of DNAs of increasing length with the alkylated base out of phase (16 base-pairs apart) or in phase (21 base-pairs apart) with the helical repeat of the DNA. The DNA contained the sequence 5' CAA 3', which is the 61st codon of the K-ras gene, because this codon is a preferred site of mutation for a number of carcinogens including the methylating carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK). O4 Methylthymine or O4-ethylthymine replaced thymine in either of the two A.T base pairs of this codon (normally CAA), and O6-methylguanine replaced the guanine in the G.C pair. All the sequences containing O4-alkylthymine exhibited anomalous, slow, gel migration and ligated to form circles of unusually small diameter. In general, the effect was seen when the alkylated base-pair was out of phase with the helical repeat as well as when it was in phase, suggesting that the alkylated base-pair confers flexibility which is largely isotropic, i.e., has no preferred direction, rather than anisotropic flexibility or bending. However, at pH 8.3 the 21-base-pair set containing O4-alkylT.A had significantly greater anomalous migration than the 16-base-pair set, suggesting that the flexibility produced by this base-pair has a significant anisotropic component and thus resembles true bending.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751492 TI - Fidelity of mammalian DNA replication and replicative DNA polymerases. AB - Current models suggest that two or more DNA polymerases may be required for high fidelity semiconservative DNA replication in eukaryotic cells. In the present study, we directly compare the fidelity of SV40 origin-dependent DNA replication in human cell extracts to the fidelity of mammalian DNA polymerases alpha, delta, and epsilon using lacZ alpha of M13mp2 as a reporter gene. Their fidelity, in decreasing order, is replication greater than or equal to pol epsilon greater than pol delta greater than pol alpha. DNA sequence analysis of mutants derived from extract reactions suggests that replication is accurate when considering single-base substitutions, single-base frameshifts, and larger deletions. The exonuclease-containing calf thymus DNA polymerase epsilon is also highly accurate. When high concentrations of deoxynucleoside triphosphates and deoxyguanosine monophosphate are included in the pol epsilon reaction, both base substitution and frameshift error rates increase. This response suggests that exonucleolytic proofreading contributes to the high base substitution and frameshift fidelity. Exonuclease-containing calf thymus DNA polymerase delta, which requires proliferating cell nuclear antigen for efficient synthesis, is significantly less accurate than pol epsilon. In contrast to pol epsilon, pol delta generates errors during synthesis at a relatively modest concentration of deoxynucleoside triphosphates (100 microM), and the error rate did not increase upon addition of adenosine monophosphate. Thus, we are as yet unable to demonstrate that exonucleolytic proofreading contributes to accuracy during synthesis by DNA polymerase delta. The four-subunit DNA polymerase alpha-primase complex from both HeLa cells and calf thymus is the least accurate replicative polymerase. Fidelity is similar whether the enzyme is assayed immediately after purification or after being stored frozen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751493 TI - Arginine-395 is required for efficient in vivo and in vitro aminoacylation of tRNAs by Escherichia coli methionyl-tRNA synthetase. AB - We have previously shown that the anticodon of methionine tRNAs contains the major recognition site required for aminoacylation of tRNAs by Escherichia coli methionyl-tRNA synthetase (MetRS) and have located part of the anticodon binding domain on the enzyme at a site close to Trp461 [Schulman, L. H., & Pelka, H. (1988) Science 242, 765-768; Ghosh, G., Pelka, H., & Schulman, L.H. (1990) Biochemistry 29, 2220-2225]. In order to gain information about other possible sites of contact between MetRS and its tRNA substrates, we have examined the effects of mutations at a series of positively charged residues on the surface of the C-terminal domain of the enzyme. Conversion of Arg356, Arg366, Arg380, or Arg453 to Gln had little or no effect on enzyme activity. Similarly, conversion of Lys402 or Lys439 to Asn failed to significantly alter aminoacylation activity. Conversion of Arg380 to Ala or Arg442 to Gln produced a 5-fold reduction in kcat/Km for aminoacylation of tRNAfMet, with no effect on methionine activation, indicating a possible minor role for these residues in interaction of the enzyme with the tRNA substrate. In contrast, mutation of a phylogenetically conserved residue, Arg395, to Gln increased the Km for aminoacylation of tRNAfMet about 30 fold and reduced kcat/Km by 25,000-fold. The mutant enzyme was also shown to be highly defective by its inability to complement a strain of E. coli having an altered chromosomal MetRS gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751494 TI - Use of site-directed mutagenesis to define the limits of sequence variation tolerated for processing of the M13 procoat protein by the Escherichia coli leader peptidase. AB - Leader peptidase cleaves the leader sequence from the amino terminus of newly made membrane and secreted proteins after they have translocated across the membrane. Analysis of a large number of leader sequences has shown that there is a characteristic pattern of small apolar residues at -1 and -3 (with respect to the cleavage site) and a helix-breaking residue adjacent to the central apolar core in the region -4 to -6. The conserved sequence pattern of small amino acids at -1 and -3 around the cleavage site most likely represents the substrate specificity of leader peptidase. We have tested this by generating 60 different mutations in the +1 to -6 domain of the M13 procoat protein. These mutants were analyzed for in vivo and in vitro processing, as well as for protein insertion into the cytoplasmic membrane. We find that in vivo leader peptidase was able to process procoat with an alanine, a serine, a glycine, or a proline residue at -1 and with a serine, a glycine, a threonine, a valine, or a leucine residue at -3. All other alterations at these sites were not processed, in accordance with predictions based on the conserved features of leader peptides. Except for proline and threonine at +1, all other residues at this position were processed by leader peptidase. None of the mutations at -2, -4, or -5 of procoat (apart from proline at -4) completely abolished leader peptidase cleavage in vivo although there were large effects on the kinetics of processing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751495 TI - Determination of peptide regions on the surface of the eubacterial and archaebacterial ribosome by limited proteolytic digestion. AB - Limited proteolysis was used in combination with two-dimensional gel electrophoresis, blotting, and amino acid sequence analysis to investigate the surface of intact ribosomal subunits at the peptide and amino acid level. Surface sites of 14 ribosomal proteins from Escherichia coli 50S subunits were determined using proteases with different specificities. To assess the evolutionary conservation of ribosomal topography among eubacteria, large subunits from Bacillus stearothermophilus were also subjected to limited proteolysis. The results obtained indicate a conservation of the three-dimensional ribosomal structure at the peptide level. The data for the eubacterial ribosomes are in full agreement with the model of the 50S protein topography derived from immunological data. Furthermore, peptide surface regions of archaebacterial ribosomes have been investigated. The results presented in this work prove that limited proteolysis can successfully be applied to halophilic and thermophilic ribosomes from archaebacteria. PMID- 1751496 TI - Properties of lipoamide dehydrogenase altered by site-directed mutagenesis at a key residue (I184Y) in the pyridine nucleotide binding domain. AB - The binding of pyridine nucleotide to human erythrocyte glutathione reductase, an enzyme of known three-dimensional structure, requires some movement of the side chain of Tyr197. Moreover, this side chain lies very close to the isoalloxazine ring of the FAD cofactor. The analogous residue, Ile184, in the homologous enzyme Escherichia coli lipoamide dehydrogenase has been altered by site-directed mutagenesis to a tyrosine residue (I184Y) [Russell, G. C., Allison, N., Williams, C. H., Jr., & Guest, J.R. (1989) Ann. N.Y. Acad. Sci. 573, 429-431]. Characterization of the altered enzyme shows that the rate of the pyridine nucleotide half-reaction has been markedly reduced and that the spectral properties have been changed to mimic those of glutathione reductase. Therefore, Ile184 is shown to be an important residue in modulating the properties of the flavin in lipoamide dehydrogenase. Turnover in the dihydrolipoamide/NAD+ reaction is decreased by 10-fold and in the NADH/lipoamide reaction by 2-fold in I184Y lipoamide dehydrogenase. The oxidized form of I184Y shows remarkable changes in the fine structure of the visible absorption and circular dichroism spectra and also shows nearly complete quenching of FAD fluorescence. The spectral properties of the altered enzyme are thus similar to those of glutathione reductase and very different from those of wild-type lipoamide dehydrogenase. On the other hand, spectral evidence does not reveal any change in the amount of charge-transfer stabilization at the EH2 level. Stopped-flow data indicate that, in the reduction of I184Y by NADH, the first step, reduction of the flavin, is only slightly slowed but the subsequent two-electron transfer to the disulfide is markedly inhibited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751498 TI - Fluorescence assay for phospholipid membrane asymmetry. AB - Highly fluorescent 7-nitro-2,1,3-benzoxadiazol-4-yl-lipid (NBD-lipid) analogues are widely used to examine lipid transport and membrane structure. We have developed a method for chemically modifying NBD-labeled lipids in both artificial and biological membranes. This was achieved by treating fluorescently labeled membranes with dithionite (S2O4(-2)). When small unilamellar vesicles containing NBD-labeled phospholipids were reacted with dithionite, only the fluorescent lipid located on the outer leaflet of the vesicles' bilayer was reduced. Seven different NBD-lipid analogues, including a fluorescent sterol, were reduced by treatment with dithionite to nonfluorescent 7-amino-2,1,3-benzoxadiazol-4-yl lipid derivatives. To assess the feasibility of using this reagent in biological systems, N-(7-nitro-2,1,3-benzoxadiazol-4-yl)dioleoylphosphatidylethanol ami ne was inserted into the outer leaflet of the plasma membrane of CHO-K1 cells. Subsequent incubation of these cells with a nontoxic concentration of dithionite resulted in the complete loss of fluorescence from the plasma membrane. In contrast, when cells were permitted to endocytose some of their fluorescently labeled plasma membrane and then treated with dithionite, fluorescence at the plasma membrane was eliminated, while intracellular labeling was not affected. These data suggest that dithionite reacts with NBD-labeled lipids in the outer leaflet of membrane bilayers, producing nonfluorescent derivatives. We demonstrate how reduction of NBD-lipids with dithionite can be used to prepare asymmetrically labeled liposomes and to measure transverse-membrane asymmetry in vesicles. This method should be useful in many biochemical investigations, including the measurement of phospholipid translocase activity. PMID- 1751497 TI - Phospholipase A2 engineering. X-ray structural and functional evidence for the interaction of lysine-56 with substrates. AB - Site-directed mutagenesis studies of bovine pancreatic phospholipase A2 (PLA2, overproduced in Escherichia coli) showed that replacement of surface residue Lys 56 by a neutral or hydrophobic amino acid residue resulted in an unexpected and significant change in the function of the enzyme. The kcat for phosphatidylcholine micelles increases 3-4-fold for K56M, K56I, and K56F and ca. 2-fold for K56N and K56T but does not change for K56R. These results suggest that the side chain of residue 56 has significant influence on the activity of PLA2. In order to probe the structural basis for the enhanced activity, the crystal structures of wild-type and K56M PLA2 were determined by X-ray crystallography to a resolution of 1.8 A. The results suggest that the mutation has not only perturbed the conformation of the side chain of Met-56 locally but also caused conformational changes in the neighboring loop (residues 60-70), resulting in the formation of a hydrophobic pocket by residues Met-56, Tyr-52, and Tyr-69. Docking of a phosphatidylcholine inhibitor analogue into the active site of K56M, according to the structure of the complex of cobra venom PLA2 phosphatidylethanolamine inhibitor analogue [White, S.P., Scott, D. L., Otwinowski, Z., Gleb, M. H., & Sigler, P. (1990) Science 250, 1560-1563], showed that the choline moiety [N(CH3)3]+ is readily accommodated into the newly formed hydrophobic pocket with a high degree of surface complementarity. This suggests a possible interaction between residue 56 and the head group of the phospholipid, explaining the enhanced activities observed when the positively charged Lys-56 is substituted by apolar residues, viz., K56M, K56I, and K56F. Further support for this interpretation comes from the 5-fold enhancement in kcat for the mutant K56E with a negatively charged side chain, where there would be an attractive electrostatic interaction between the side chain of Glu-56 and the positively charged choline moiety. Our results also refute a recent report [Tomasselli, A. G., Hui, J., Fisher, J., Zurcher-Neely, H., Reardon, I.M., Oriaku, E., Kezdy, F.J., & Heinrikson, R.L. (1989) J. Biol. Chem. 264, 10041-10047] that substrate level acylation of Lys-56 is an obligatory step in the catalysis by PLA2. PMID- 1751499 TI - Lipid asymmetry in rabbit small intestinal brush border membrane as probed by an intrinsic phospholipid exchange protein. AB - All classes of phospholipids present in brush border membrane are exchanged in a 1:1 ratio for egg phosphatidylcholine when brush border membrane vesicles from rabbit small intestine are incubated with small unilamellar vesicles of egg phosphatidylcholine. The exchange reaction exhibits biphasic kinetics similar to those of the hydrolysis of brush border membrane phospholipids by phospholipase A2 and sphingomyelinase C. In both reactions there is an initial fast phase followed by a markedly slower one. The phospholipid exchange appears to be catalyzed by intrinsic brush border membrane protein(s), while the digestion by phospholipases is mediated by externally added enzymes. From a comparison of the kinetics of phospholipid exchange and phospholipid hydrolysis, the following conclusions can be drawn: Both sets of experiments indicate the presence of two phospholipid pools differing in the rate of phospholipid exchange and hydrolysis. Except for sphingomyelin, the size of the two phospholipid pools derived from phospholipid exchange is in good agreement with that derived from phospholipid hydrolysis. This is the main finding of this work, and on the basis of this result the two lipid pools are tentatively assigned to phospholipid molecules located on the outer and inner layer of the brush border membrane. The slow rate of phospholipid exchange reflects the rate of transverse or flip-flop movement of phospholipids. The half-time of this motion is approximately 8 h for isoelectric (neutral) phospholipids such as phosphatidylethanolamine and approximately 80 h for negatively charged phosphatidylserine and phosphatidylinositol. Isoelectric phospholipids (phosphatidylcholine, phosphatidylethanolamine) are preferentially located on the inner (cytoplasmic) side (to about 70%) while the negatively charged phospholipids are more evenly distributed: 55-60% are located on the inner side. PMID- 1751500 TI - Picosecond rotation of small polar fluorophores in the cytosol of sea urchin eggs. AB - A new fluorescence method to measure viscosity in cell cytosol [Fushimi, K., & Verkman, A. S. (1991) J. Cell Biol. 112, 719-725] has been applied to determine fluid-phase viscosity in sea urchin eggs. Freshly harvested eggs from Lytechinus pictus were loaded with the dyes 2,7-bis(2-carboxyethyl)-5-(and-6 )carboxyfluorescein (BCECF), 6-carboxyfluorescein (6CF), fluorescein, or calcein. Fluorescence lifetimes and anisotropy decay were measured in single eggs by multiharmonic, frequency-domain microfluorometry using a 1-2-micron focused laser spot and 25x air objective. In calibration solutions consisting of glycerol in pH 8 buffered sea water, probe lifetime was single exponential and probe rotation was isotropic with a single correlation time which increased linearly with viscosity in the range 1-3.6 cP. In eggs at 22 degrees C, there were single lifetimes (in nanoseconds) of 3.6 (BCECF), 3.4 (6CF), 3.2 (fluorescein), and 3.3 (calcein). Probe rotation in eggs had two components, a fast component (in picoseconds, mean +/- SE, 10-18 eggs) of 568 +/- 39 (BCECF), 311 +/- 21 (6CF), 313 +/- 15 (fluorescein), and 516 +/- 44 (calcein) and a slow component of 10-40 ns. The fractional amplitude of the fast component, corresponding to unbound dye, was 0.72-0.81. Apparent viscosities of fluid-phase cytoplasm (centipoises) given by the four different probes were in good agreement: 2.3 +/- 0.2 (BCECF), 2.1 +/- 0.1 (6CF), 2.5 +/- 0.1 (fluorescein), and 2.3 +/- 0.2 (calcein). The viscosity in cytosol of sea urchin eggs (2.1-2.5 cP) is thus relatively low, yet significantly greater than that of water (1 cP) or cytosol in cultured fibroblasts (1.2-1.4 cP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751501 TI - Reexamination of the secondary and tertiary structure of histidine-containing protein from Escherichia coli by homonuclear and heteronuclear NMR spectroscopy. AB - Analysis of the histidine-containing protein (HPr) from Escherichia coli by two dimensional homonuclear and heteronuclear nuclear magnetic resonance techniques has been performed, extending the work originally reported [Klevit, R. E., Drobny, G. D., & Waygood, E. B. (1986) Biochemistry 25, 7760-7769; Klevit, R. E., & Drobny, G. P. (1986) Biochemistry 25, 7770-7773; Klevit, R. E., & Waygood, E. B. (1986) Biochemistry 25, 7774-7781]. Two-dimensional homonuclear total coherence spectroscopy (TOCSY) allowed for more complete assignments of the side chain spin systems than had been possible in the original studies. As well, two dimensional 15N-1H heteronuclear spectroscopy was used to resolve a number of ambiguities present in the homonuclear spectra due to resonance redundancies. These analyses led to the correction of a number of resonance assignments that were made with the spectra that could be collected with the technology that existed 6 years ago. In addition, amide exchange rates and 3JNH coupling constants have been measured, extending the original analysis and yielding new structural information. All these data have been used to reexamine the folding topology of E. coli HPr. Structure calculations showed that the topology derived from the earlier NMR data, i.e., a four-stranded beta-sheet with three alpha helices running along one side of the sheet, was essentially unchanged, although at the present level of analysis, a well-defined "helix B" could not be established with high confidence. In addition, the data reported here revealed the existence of two slowly-exchanging side-chain hydroxyl protons belonging to Ser31 and Thr59. Their behavior strongly suggests that these side chains are involved in hydrogen bonds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751503 TI - Preliminary results suggesting exaggerated ovarian androgen production early in the course of polycystic ovary syndrome. PMID- 1751502 TI - Double standard, double jeopardy: research on health problems of adolescent women. PMID- 1751504 TI - Fat and protein composition of mature milk in adolescents. AB - The levels of certain components, notably total protein, total fat, energy, and fatty acids, of mature milk from 48 adolescent and 44 adult mothers was studied. These two groups were subdivided into high and low socioeconomic level (SEL). All mothers were primiparous, eutrophic, and with term pregnancy; and their newborns weighted over 2500 g at birth. The age factor appeared to have significant influence on the concentration of total protein, with higher levels in the group of adolescent mothers possibly as a compensatory mechanism to maintain the caloric value of the milk. The fatty acid content was altered significantly by the SEL probably due to the direct effect of maternal diet. The milk in adolescent mothers of low SEL demonstrated higher concentration of lauric and myristic acids, while the milk in low SEL adults contained higher proportions of linoleic and linolenic acids. The milk in adult mothers of high SEL demonstrated higher concentrations of palmitic, palmitoleic, and oleic acids. The different feeding habits of two socioeconomic groups may explain these results. The regular intake of soya oil, corn oil, and margarine by the urban population in general resulted in higher levels of linoleic acid in the milk of all groups studied. PMID- 1751505 TI - Use of the pen delivery system for intensive insulin therapy in college-age students with type I diabetes. AB - The present report describes our experience with 16 adolescents and young adults with insulin-dependent diabetes mellitus (IDDM; Type I) who switched from two injections of insulin per day to the NovolinPen and four insulin injections a day. Their mean age at the initiation of therapy was 19.2 years with a duration of diabetes of 8.9 years. Sixteen random computer-matched (for age, sex, and duration of diabetes) controls who remained on two insulin injections a day were evaluated for comparison. Most subjects were preparing to leave home for college. After a minimum of 1 year of using the pen, the mean weight gain of the test subjects was significantly greater (P less than .05) than for the computer matched controls. Glycemic control, as monitored by mean HbA1c values, were similar for the NovolinPen and the control groups (10.8 versus 10.9, respectively) after almost 2 years. The main advantage to the pen expressed by the users was a sense of freedom of lifestyle. PMID- 1751506 TI - Eating attitudes, health-risk behaviors, self-esteem, and anxiety among adolescent females in a suburban high school. AB - In order to determine whether adolescent females with abnormal eating attitudes display lower levels of self-esteem and higher levels of anxiety than their peers, and whether these adolescents participate in health-risk behaviors to a greater or lesser degree than their peers, we administered a series of questionnaires to the females attending a suburban high school in New York State. The questionnaires, completed by 268 students (mean age, 16.2 years), included data on health-risk behaviors and weight attitudes, an Eating Attitudes Test, a self-esteem scale, and an anxiety inventory. Results indicated that almost two thirds of the students described themselves as overweight, almost three-quarters felt they were above the healthiest weight for their age and height, and almost four-fifths were above the weight at which they would be most happy; 18% of the students scored 30 or more on the Eating Attitudes Test, a score suggestive of an eating disorder. Use of Spearman-rank correlation coefficients and multiple linear regression analysis revealed that those with more unhappiness with their weight and higher scores on the eating attitudes test were more likely to have lower self-esteem and higher anxiety and to participate more in health-risk behaviors, including cigarette smoking, alcohol use, drug use, and sexual activity with more total partners. The data from this study further corroborate the growing belief that health-risk behaviors tend to cluster together in vulnerable adolescents and demonstrate that abnormal eating attitudes and behaviors may be part of this cluster, especially in females with low self-esteem and high levels of anxiety. PMID- 1751507 TI - Predictors of HIV-preventive sexual behavior in a high-risk adolescent population: the influence of perceived peer norms and sexual communication on incarcerated adolescents' consistent use of condoms. AB - Data were collected from 112 sexually active adolescents incarcerated in a juvenile detention facility to identify predictors of consistent use of condoms during sexual intercourse. Adolescents completed an anonymous epidemiologic survey instrument developed by the Centers for Disease Control. The self-report survey assessed demographic, psychosocial, and behavioral factors. Three factors were identified as associated with consistent condom use. These significant bivariate factors were entered into a multivariate logistic regression model to identify the independent contribution of each factor. Non-Black adolescents, adolescents who communicate with their sex partners about AIDS, and those who perceive peer norms as supporting condom use were significantly more likely to be consistent condom users. The findings suggest that Human Immunodeficiency Virus (HIV) prevention programs for incarcerated adolescents that emphasize training in communication skills and modifying perceptions of peer normative behavior may be more effective in increasing the adoption and maintenance of condom use. PMID- 1751508 TI - Self-reported health concerns and sexual behaviors in adolescents with cervical dysplasia. A pilot study. AB - A group of 46 women attending an adolescent dysplasia clinic were surveyed regarding the reported impact of cervical dysplasia on sexual beliefs and behaviors. The adolescents reported being concerned about their future health and having changed their sexual practices. There were no clear relationships between demographic variables or sexual attitudes and changes. The adolescents' self reports of their behavior were not consistent; those adolescents who reported safer sex practices did not have lower rates of sexually transmitted diseases postbiopsy. The results of this study indicate the important but complex impact of sexually transmitted disease on adolescents and suggests that this impact on adolescents may be different from that on adults. PMID- 1751509 TI - Chronic fibrosing pancreatitis in a 12-year-old female. AB - Recurrent abdominal pain in an adolescent population is a frequent complaint. However, diseases of the pancreas, and especially chronic pancreatitis, in this age group are extremely uncommon. One type of pancreatitis, fibrosing pancreatitis, has been reported in only 14 previous pediatric patients, five of whom were over 12 years of age. We report an additional 12-year-old female with this condition. This case serves to remind us that fibrosing pancreatitis needs to be considered in any adolescent patient with chronic abdominal pain, recurrent vomiting, weight loss, steatorrhea, and painless obstructive jaundice. PMID- 1751510 TI - Cerebral infarct associated with lupus anticoagulant in an adolescent girl: a case report with review of the literature. AB - A 15-year-old girl with right-sided cerebral infarct in association with lupus anticoagulant is described. The literature on the primary antiphospholipid syndrome and its neurological complications is reviewed. PMID- 1751511 TI - Exacerbation of fibrous dysplasia associated with an adolescent pregnancy. AB - Fibrous dysplasia is a metabolic skeletal disorder in which the medullary spaces of affected bones are replaced by fibro-osseous tissue. Patients with fibrous dysplasia usually become symptomatic during childhood; the adolescent patient we describe is unusual because she was not known to suffer from fibrous dysplasia until she became pregnant and experienced a dramatic reactivation of the symptoms. The therapeutic implication of this case and reproductive counselling for young women with fibrous dysplasia are discussed. PMID- 1751512 TI - Synaptin/synaptophysin, p65 and SV2: their presence in adrenal chromaffin granules and sympathetic large dense core vesicles. AB - The subcellular distribution of three proteins of synaptic vesicles (synaptin/synaptophysin, p65 and SV2) was determined in bovine adrenal medulla and sympathetic nerve axons. In adrenals most p65 and SV2 is confined to chromaffin granules. Part of synaptin/synaptophysin is apparently also present in these organelles, but a considerable portion is found in a light vesicle which does not contain significant concentrations of typical markers of chromaffin granules (cytochrome b-561, dopamine beta-hydroxylase or the amine carrier). An analogous finding was obtained for sympathetic axons. The large dense core vesicles contain most p65 and also SV2 but only a smaller portion of synaptin/synaptophysin. A lighter vesicle containing this latter antigen and some SV2 has also been found. These results establish that in adrenal medulla and sympathetic axons three typical antigens of synaptic vesicles are not restricted to light vesicles. Apparently, a varying part of these antigens is found in chromaffin granules and large dense core vesicles. On the other hand, the light vesicles do not contain significant concentrations of functional antigens of chromaffin granules. Thus, the biogenesis of small presynaptic vesicles which contain all three antigens as well as functional components like the amine carrier is likely to involve considerable membrane sorting. PMID- 1751513 TI - Distribution of control of oxidative phosphorylation in mitochondria oxidizing NAD-linked substrates. AB - The flux control distribution of the net rate of state 3 respiration was determined in heart and kidney mitochondria incubated with low concentrations of pyruvate (0.5 mM) or 2-oxoglutarate (1 mM), and in conditions that led to activation of NAD-linked dehydrogenases, i.e., high substrate or Ca2+ concentrations. Control of flux was exerted by the ATP/ADP carrier (flux control coefficient, ci = 0.37) and Site 1 of the respiratory chain (ci = 0.28) when dehydrogenase activity was low. Control of the process shifted to the ATP synthase (ci = 0.32) and the Pi carrier (Ci = 0.27) when dehydrogenases were activated by high pyruvate and high Ca2+. The changes in the control exerted by the ATP/ADP carrier and the ATP synthase were not due to changes in the transmembrane potential, nor to a modification of intramitochondrial ATP/ADP ratios. Applying the summation theorem of the control analysis, it was found that at low Ca2+ and pyruvate concentrations the dehydrogenases shared the control of state 3 respiration with other steps. The NAD-linked dehydrogenases did not exert any significant control at high Ca2+ or high pyruvate concentrations. PMID- 1751514 TI - Respiration in non-phosphorylating yeast mitochondria. Roles of non-ohmic proton conductance and intrinsic uncoupling. AB - Respiratory rate, protonmotive force and charge/O ratio were measured under two different kinds of steady state in non-phosphorylating yeast mitochondria: (i) when the electron flux was modulated by a variable limitation in electron supply or (ii) when oxygen consumption was decreased by respiratory chain inhibitor titration. We showed that the relationships between either delta p or charge/O ratio and respiratory rate are different under the two kinds of steady state, indicating different degrees of intrinsic uncoupling in respiratory chain. Moreover, we observed a non-ohmic dependence between H(+)-conductance and delta p. We concluded that the high rate of static-head respiration in yeast mitochondria was determined both by the non-ohmic proton conductance of the inner membrane and the saturation of the redox proton pump slipping. PMID- 1751515 TI - Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. I. Basic characteristics and effects of D-glucose and insulin. AB - The basic characteristics of hexose uptake and regulation of the glucose transporter (GLUT1) by D-glucose and insulin were studied in primary cultures of bovine brain microvessel endothelial cells (BMECs). A non-metabolizable glucose analog, 3-O-[3H]methyl-D-glucose [( 3H]3MG), was used as a model substrate, and the uptake was studied using BMECs grown in tissue culture plates. Uptake of [3H]3MG was equilibrative, temperature-dependent, and independent of sodium. The uptake also decreased gradually with culture age from 7 to 13 days. Saturation kinetics were observed for [3H]3MG uptake and the apparent Km and Vmax values were determined to be 13.2 mM and 169 nmol/mg per min, respectively. Pre incubation with high concentrations of D-glucose and 3MG accelerated [3H]3MG uptake by BMECs by a counter-transport mechanism. D-Glucose, 2-deoxy-D-glucose, D mannose, D-xylose, D-galactose and D-ribose showed significant competitive inhibition with [3H]3MG, whereas L-glucose, D-fructose, and sucrose did not affect [3H]3MG uptake by BMECs. [3H]3MG uptake was inhibited significantly by cytochalasin B and phloretin but not by phlorizin, 2,4-dinitrophenol, or ouabain. D-Glucose starvation of BMECs by incubation with D-glucose-free media for 24 h resulted in a significant increase (40-70%) in uptake of [3H]3MG compared with control conditions (7.3 mM D-glucose). Low D-glucose treatments (2.43 and 1.83 mM) for 7 days induced a slight but significant increase (20%) in [3H]3MG uptake, while long-term high glucose treatments (25 mM) showed no significant effect on [3H]3MG uptake irrespective of exposure time. The increase in [3H]3MG accumulation following D-glucose starvation was dependent upon starvation time (12 to 48 hr) and protein synthesis. Refeeding of D-glucose (7.3 mM) to D-glucose starved BMECs resulted in a return of [3H]3MG uptake to control levels in 48 h. The D-glucose-starvation-induced increase in [3H]3MG uptake was shown to result from an increase in Vmax; the Km remained constant. In addition, D-glucose starved BMECs were shown to have an increased level of GLUT1 using an antibody against human GLUT1 and an enzyme-linked immunosorbent assay (ELISA). The increased uptake following D-glucose starvation was not significantly affected by the presence of L-glucose, was partially impaired by the presence of D-galactose, D-fructose, and D-xylose, and was completely inhibited by the presence of D mannose and 3MG. Furthermore, preincubation of BMECs with insulin (10 micrograms/ml) for 20 min did not affect the uptake of [3H]3MG or 2-deoxy-D [3H]glucose ([3H]2DG).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1751516 TI - Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. II. Effects of conditioned media from astroglial and glioma cells. AB - Regulation of glucose uptake by an astroglial cell secreted factor(s) was studied in primary cultures of brain microvessel endothelial cells (BMECs). Uptake of a non-metabolizable glucose analog, 3-O-[3H]methyl-D-glucose ([3H]3MG), was measured after the BMECs were treated with media conditioned by primary cultures of rat astrocytes (Astrocyte Conditioned Media: ACM) or rat C6 glioma cells (Glioma Cell Conditioned Media: GCM). Uptake of [3H]3MG was significantly increased by ACM (30-50%) and GCM (60-200%) treatments, whereas conditioned medium from 3T3 fibroblasts (3T3) caused no significant effect. The elevation in [3H]3MG uptake increased with increasing time of exposure of BMECs to these conditioned media (CM), and the effect was shown to be reversible. Glucose depletion of CM was shown not to be a factor. The presence of cycloheximide, a protein synthesis inhibitor, during treatment of the BMECs with ACM and GCM blocked the increase in [3H]3MG uptake by the cells. These results suggested that ACM or GCM treatment elevated de novo synthesis of brain-type glucose transporter (GLUT1). Indeed, enhanced GLUT1 expression by these treatments in BMECs was demonstrated directly by enzyme-linked immunosorbent assay (ELISA) using antibodies against human GLUT1. After trypsinization of ACM and GCM, both conditioned media still induced significant stimulation of [3H]3MG uptake by BMECs. A significant increase in [3H]3MG uptake was also observed when ACM or GCM was exposed to BMECs through a dialysis membrane with a molecular weight cutoff of 1000. To examine whether the effects were specific to brain endothelial cells, [3H]3MG uptake experiments were performed employing aortic endothelial cells (AECs), pulmonary microvessel endothelial cells (PMECs), and 3T3 cells. ACM treatment did not alter 3MG uptake by these cells, suggesting that the ACM effect was specific to BMECs. On the other hand, [3H]3MG uptake by AECs and PMECs treated with GCM was significantly enhanced. The present study demonstrated that some factor(s) of relatively small molecular weight, which was released from astrocytes or glioma cells, stimulated glucose uptake by enhancing GLUT1 synthesis in BMECs. PMID- 1751517 TI - Cation and harmaline interactions with Na(+)-independent dibasic amino acid transport system y+ in human erythrocytes and in erythrocytes from a primitive vertebrate the pacific hagfish (Eptatretus stouti). AB - Transport systems y+, asc and ASC exhibit dual interactions with dibasic and neutral amino acids. For conventional Na(+)-dependent neutral amino acid system ASC, side chain amino and guanido groups bind to the Na+ site on the transporter. The topographically equivalent recognition site on related system asc binds harmaline (a Na(+)-site inhibitor) with the same affinity as asc (apparent Ki range 1-4 mM), but exhibits no detectable affinity for Ha. Although also classified as Na(+)-independent, dibasic amino acid transport system y+ accepts neutral amino acids when Na+ or another acceptable cation is also present. This latter observation implies that the y+ translocation site binds Na+ and suggests possible functional and structural similarities with ASC/asc. In the present series of experiments with human erythrocytes, system y(+)-mediated lysine uptake (5 microM, 20 degrees C) was found to be 3-fold higher in isotonic sucrose medium than in normal 150 mM NaCl medium. This difference was not a secondary consequence of changes in membrane potential, but resulted from Na+ functioning as a competitive inhibitor of transport. Apparent Km and Vmax values for lysine transport at 20 degrees C were 15.2 microM and 183 mumol/l cells per h, respectively, in sucrose medium and 59.4 microM and 228 mumol/l cells per h in Na+ medium. Similar results were obtained with y+ in erythrocytes of a primitive vertebrate, the Pacific hagfish (Eptatretus stouti), indicating that Na(+) inhibition is a general property of this class of amino acid transporter. At a permeant concentration of 5 microM, the IC50 value for Na(+)-inhibition of lysine uptake by human erythrocytes was 27 mM. Other inorganic and organic cations, including K+ and guanidinium+, also inhibited transport. In parallel with its actions on ASC/asc harmaline competitively inhibited lysine uptake by human cells in sucrose medium. As predicted from mutually competitive binding to the y+ translocation site, the presence of 150 mM Na+ increased the harmaline inhibition constant (Ki) from 0.23 mM in sucrose medium to 0.75 mM in NaCl medium. We interpret these observations as further evidence that y+, asc and ASC represent a family of closely related transporters with a common evolutionary origin. PMID- 1751518 TI - Phospholipid acylation by mouse sciatic nerve microsomes. AB - The partition of 0.3 nmol of [1-14C]oleoyl-CoA in the microsomes (10 micrograms proteins) from mouse sciatic nerves is unaffected by the presence of lysophospholipids and is about 45% of the total oleoyl-CoA (77% of the acylglycerophosphocholine partition in the membrane). The concentration of both oleoyl-CoA and acylglycerophosphocholine is over 1 mM in the membrane. There is a selective acyl transfer from acyl-CoA to lysolipid acceptors (oleoyl greater than myristoyl, palmitoyl, stearoyl much greater than eicosanoyl greater than docosanoyl, tetracosanoyl). The exogenous acyl acceptors are acylglycerophosphocholine and acylglycerophosphoinositol and to a lesser extent acylglycerophosphoethanolamine, but not acylglycerophosphoserine. A PC formation from acylGPC in the absence of exogenous acyl donors or from oleoyl-CoA in the absence of exogenous acyl acceptor was also observed. PMID- 1751519 TI - Monensin blocks the transfer of very long chain fatty acid containing lipids to the plasma membrane of leek seedlings. Evidence for lipid sorting based on fatty acyl chain length. AB - Delivery of newly synthesized fatty acids and lipids to the plasma membrane in leek seedlings via the endoplasmic reticulum (ER)-Golgi apparatus pathway is primarily by bulk transport (without sorting). However, pulse-chase experiments revealed kinetics of transport of lipids with VLCFA (very long chain fatty acids having more than 18 carbon atoms) in favor of a preferential transfer of these molecules to the plasma membrane. Use of monensin showed the accumulation of lipids in the Golgi apparatus and a related decrease of the amount of lipids transported to the plasma membrane. Lipid and fatty acid analyses revealed that transport of VLCFA-containing phospholipids was most strongly inhibited by the monensin block. These results taken together with an inability of the plasma membrane to synthesize VLCFA support a role for the Golgi apparatus in VLCFA delivery to the plasma membrane and leads to the hypothesis of a sorting function as well, based on fatty acyl chain length. PMID- 1751520 TI - Influx and incorporation into protein of L-phenylalanine in the perfused rat pancreas: effects of amino acid deprivation and carbachol. AB - The rate of protein synthesis in the isolated perfused rat pancreas was measured from the rate of incorporation of L-[3H]phenylalanine into total protein, and was compared with the transport of this amino acid into the epithelium. Unidirectional (15 s) and net (15-30 min) uptake of L-[3H]phenylalanine was measured relative to D-[14C]mannitol (extracellular marker) using a cell loading technique. The fractional rate of protein synthesis in the pancreas was also measured in vivo using a flooding dose technique and found to be 118 +/- 10% day 1 (corresponding to an absolute rate of incorporation of L-Phe into protein of 36.1 +/- 3 nmol min-1 g-1) in overnight fasted rats. Compared with the in vivo rate, the perfused pancreas exhibited a markedly lower rate of protein synthesis which increased significantly when amino acids were added to the perfusate (15.6 +/- 1.9 vs. 22.5 +/- 0.9% day-1 or 4.7 +/- 0.6 vs. 6.9 +/- 0.3 nmol L-Phe min-1 g 1). Carbachol (3 x 10(-7) M) stimulated protein synthesis provided amino acids were also supplied in the perfusate. Protein synthesis rates measured under all conditions in vivo and in vitro were at least an order of magnitude lower than the unidirectional influx (121 +/- 14 nmol min-1 g-1) of L-phenylalanine into the pancreatic epithelium. These results demonstrate that amino acid transport across the basolateral membrane of the epithelium is not rate-limiting for pancreatic protein synthesis. PMID- 1751521 TI - A neutron diffraction study of the influence of ions on phospholipid membrane interactions. AB - Neutron diffraction is used to examine the effects of Ca2+ and ClO4- ions on interactions and some structural features of dipalmitoylphosphatidylcholine membranes in both solid and fluid lamellar phases. The results are described within the framework of Derjaguin-Landau-Verwey-Overbeek (DLVO) theory with reference to electrostatic, van der Waals, and hydration components of disjoining pressure. The Hamaker constants are evaluated under equilibrium conditions. Addition of 100 mM CaCl2 to the aqueous phase substantially increases the lamellar repeat spacing (d), which is interpreted in terms of adsorption of Ca2+ ions to bilayers followed by electrostatic repulsion between membranes. The rise of NaClO4 concentration in the presence of 100 mM CaCl2 leads to gradual decrease in d, evidently resulted from the diminution of Ca(2+)-induced positive surface potential by both electrostatic screening and binding of ClO4- ions. In the absence of CaCl2, elevation of NaClO4 concentration to 100-300 mM drastically enhances the repeat spacing and then dramatically decreases d at about 1 M NaClO4. Estimation of the hydration coefficients showed that the pronounced decrease of the repeat spacing at high NaClO4 concentrations was resulted mainly from the (partial) disruption of the structure of intermembrane bound water by chaotropic ClO4- ions and subsequent decrease in hydration repulsive pressure. Moreover, in the case of solid membranes (20 degrees C) high concentrations of ClO4- induced formation of interdigitated phase paralleled with marked reduction in bilayer thickness and corresponding increase in the effective cross-sectional area per lipid molecule. PMID- 1751522 TI - Adenine and hypoxanthine transport in human erythrocytes: distinct substrate effects on carrier mobility. AB - Transport of adenine and hypoxanthine in human erythrocytes proceeds via two mechanisms: (1) a common carrier for both nucleobases and (2) unsaturable permeation 4-5-fold faster for adenine for hypoxanthine. The latter process was resistant to inactivation by diazotized sulfanilic acid. Carrier mediated transport of both substrates was investigated using zero-trans and equilibrium exchange protocols. Adenine displayed a much higher affinity for the carrier (Km approximately 5-8 microM) than hypoxanthine (Km approximately 90-120 microM) but maximum fluxes at 25 degrees C were generally 5-10-fold lower for adenine (Vmax approximately 0.6-1.4 pmol/microliters per s) than for hypoxanthine (Vmax approximately 9-11 pmol/microliters per s). The carrier behaved symmetrically with respect to influx and efflux for both substrates. Adenine, but not hypoxanthine reduced carrier mobility more than 10-fold. The mobility of the unloaded carrier, calculated from the kinetic data of either hypoxanthine or adenine transport, was the same thus providing further evidence that these substrates share a common transporter and that their membrane transport is adequately described by the alternating conformation model of carrier-mediated transport. PMID- 1751523 TI - Interaction of positively-charged liposomes with blood: implications for their application in vivo. AB - Liposomes with positively-charged lipid components have previously demonstrated efficacy in animal models for human diseases, and are currently being evaluated in human clinical studies. Cationic lipids can improve entrapment efficiency of drugs and other substances which are negatively charged, and facilitate penetration of biological membranes in vitro, e.g. in transfection. However, toxic effects have also been reported for positively-charged liposomes containing stearylamine. In this report we have examined gross interactions between plasma components or erythrocytes with cholesterol-rich SUV composed of PC or DPPC and having 0-50 mol% of phospholipid replaced with positively-charged stearylamine, DOTMA, or BisHOP. Plasma interactions observed included increased turbidity of the usually clear stroma and/or formation of a clot-like mass. At plasma concentrations of 0.25 mumol/ml or more, the extent of plasma interactions depended upon the concentration of positive charge, the charge density of cationic lipid initially present in the liposomes, and to a lesser degree, the nature of the lipid providing the positive charge. At liposomal positive charge concentrations of greater than 0.5 mumol/ml plasma, stearylamine provoked a strong increase in plasma turbidity, whereas liposomes incorporating DOTMA or BisHOP provoked a strong clotting response. Some hemolysis of erythrocytes in vitro occurred on interaction with cationic liposomes where positive charge was contributed by DOTMA or stearylamine, but not BisHOP. Implications for the clinical use of liposomes containing cationic lipids, is discussed. PMID- 1751524 TI - The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria. AB - The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria was examined. It was found that the rate of phosphate transport is reduced (around 40%) in mitochondria from hypothyroid rats compared to that obtained in mitochondria from normal rats. Treatment of hypothyroid rats with thyroid hormone reverses this effect completely. Kinetic analysis of the phosphate transport indicates that only the Vmax of this process is affected, while there is no change in the Km values. The lower rate of phosphate transport in mitochondria from hypothyroid rats is also demonstrated by swelling experiments. There is no significant difference either in the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The hepatic mitochondrial lipid composition is altered significantly in hypothyroid rats. The total cholesterol increases, the phospholipids decrease and the cholesterol/phospholipid molar ratio increases (around 40%). Among the phospholipids, cardiolipin shows the greatest alteration (30% decrease in the hypothyroid rats). The phosphatidylethanolamine/phosphatidylcholine ratio also decreases. Alterations were also found in the pattern of fatty acids. These changes in lipid composition may be responsible, at least in part, for the depression of the phosphate carrier activity in mitochondria from hypothyroid rats. PMID- 1751525 TI - Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. AB - Therapeutic applications of intravenously injected liposomes have been limited by their rapid clearance from the bloodstream and their uptake by the macrophage cells of the liver and spleen (RES). Recently, however, liposomes which substantially evade the rapid uptake by the RES have been introduced. Since these liposomes exhibit dramatically different pharmacokinetics and biodistribution, new therapeutic opportunities have appeared. These include enhanced efficacy of antineoplastic agents against tumors, sites of inflammation, and targeting ligand coupled liposomes to extravascular targets. Despite extensive experimental work, the mechanism underlying the ability of liposomes to avoid the rapid uptake by the RES is still not fully understood. Our approach is an alternative to seeking the answers in complex differential interactions of liposomes with various components of blood. We believe that the effect can be easily explained, at least in qualitative terms, by the fundamental principles of colloid stability. In this communication, we propose that steric stabilization of liposomes is responsible for their prolonged circulation times. We propose that stabilization results from local surface concentration of highly hydrated groups that sterically inhibit both electrostatic and hydrophobic interactions of a variety of blood components at the liposome surface. PMID- 1751526 TI - Goat sperm membrane: lectin-binding sites of sperm surface and lectin affinity chromatography of the mature sperm membrane antigens. AB - The cell surface glycoproteins of goat epididymal maturing spermatozoa have been investigated using lectins as surface probes that interact with specific sugars with high affinity. Concanavalin A (ConA) and wheat-germ agglutinin (WGA) showed high affinity for mature cauda epididymal sperm agglutination, whereas RCA2, kidney beans lectin and peanut agglutinin caused much lower or little agglutination of the cells. The mature sperm exhibited markedly higher efficacy than the immature caput epididymal sperm for binding both ConA and WGA, as evidenced by sperm agglutination and the binding of the fluorescence isothiocyanate (FITC)-labelled lectins. FITC-ConA binds uniformly to the entire mature sperm surface whereas FITC-WGA binds to the acrosomal cap region of the head. The FITC-RCA2 mainly labelled the posterior head of mature cauda sperm. However, no WGA-specific glycoprotein receptors could be detected in sperm plasma membrane (PM) by WGA-Sepharose affinity chromatography. The data implied that the epididymal sperm maturation is associated with a marked increase in the ConA/WGA receptors and that WGA receptors may be glycolipids rather than glycoproteins. Analysis of the ConA receptors of cauda sperm PM identified by ConA-Sepharose affinity chromatography and subsequent resolution in SDS-PAGE demonstrated the presence of five glycopolypeptides of different concentrations (98, 96, 43, 27 and 17 kDa) of goat sperm membrane. The immunoblot of these ConA-specific glycopeptides with anti-sperm membrane antiserum showed that 98- and 96-kDa receptors are immunoresponsive. PMID- 1751527 TI - Platelet glycoprotein IIb-IIIa is associated with 21-kDa GTP-binding protein. AB - Platelet membrane glycoprotein IIb-IIIa has been widely studied in the last years because of its role as an activation-dependent, adhesive protein receptor. Recently we demonstrated that occupancy of glycoprotein IIb-IIIa-receptor sites by specific ligands exerts an inhibitory effect on platelet responses induced by mild stimulation, leading us to suppose that this event may interact with activation pathways. Although the mechanisms of signal transduction in human platelets are not completely elucidated, the hypothesis that GTP-binding proteins are involved is generally accepted. Our results demonstrate that platelet ConA receptors, known to be located mainly on GP IIb-IIIa, are able to bind [35S]GTP gamma S; the GTP-binding activity is specific and is due to the association with the receptors of two G-proteins, with apparent molecular masses of 25 and 21 kDa, respectively. After the purification of GP IIb-IIIa, a glycoprotein complex electrophoretically pure was obtained that was still associated with a GTP binding activity, migrating in SDS-polyacrylamide gel electrophoresis as a narrow band of about 21 kDa. PMID- 1751528 TI - Caco-2 cell line: a system for studying intestinal iron transport across epithelial cell monolayers. AB - Iron transport across polarized intestinal epithelium was studied by using Caco-2 cells grown in bicameral chambers. When cells were grown under conditions of low, normal, or high iron concentration not only was the iron content of the cells markedly altered but the low iron cells exhibited a nearly 2-fold increase in transepithelial electrical resistance (TEER). 59Fe uptake from the apical surface into cells and transport into the basal chamber was affected both by the valency of the iron and the iron status of the cells. Uptake from 59Fe(II)-ascorbate was about 600 pmol 59Fe/h per mg protein, increased about 2-fold in low iron cells, and was about 13-200-fold greater than uptakes from 59Fe(III) chelated to nitrilotriacetic acid, BSA, or citrate. Transport into the basal chamber from 59Fe(II)-ascorbate was 3.7 +/- 1.7 pmol/h per cm2 for Fe-deficient cells vs. 0.72 +/- 0.1 pmol/h per cm2 for normal-Fe cells and from 59Fe(III)-BSA 1.1 +/- 0.2 pmol/h per cm2 vs. 0.3 +/- 0.03 pmol/h per cm2 for deficient vs. normal iron cells, respectively. The greater transport of iron both from Fe(II) and in iron deficient cells supports the use of the Caco-2 cells as a model for iron transport. PMID- 1751529 TI - Separation of large unilamellar liposomes from blood components by a spin column procedure: towards identifying plasma proteins which mediate liposome clearance in vivo. AB - In order to facilitate the isolation of liposomes from blood components, we have developed a simple and rapid procedure combining chromatographic and centrifugal methods. This 'spin column' procedure was used to isolate liposomes from incubation mixtures with human serum or from the blood of CD1 mice after intravenous administration of liposomes. An advantage of this procedure is that processing times are fast (typically minutes) such that the isolation procedure can be done in the absence of chelators or other coagulation inhibitors which may affect protein/liposome interactions. Furthermore, several samples can be analyzed together and small sample volumes can be processed. In addition, we show that this spin column procedure can be employed to isolate large unilamellar vesicles averaging 100 nm in diameter from lipoproteins and plasma proteins. The applicability of this spin column procedure in studying protein/liposome interactions is demonstrated by quantitating the amount of human complement component C3 bound per liposome using a C3 competitive ELISA assay after incubation with human serum. The proteins associated with the recovered liposomes were further analyzed by conventional SDS-polyacrylamide gel electrophoresis. We show that egg phosphatidylcholine/cholesterol (55:45, mol/mol) or egg phosphatidylcholine/cholesterol/dioleoylphosphatidylserine (35:45:20, mol/mol) liposomes isolated from the circulation of CD1 mice within minutes of administration have distinct, complex profiles of associated proteins. By isolating circulating large unilamellar liposomes using the spin column method and characterizing the proteins associated with their membranes, this protein fingerprinting approach will expedite identifying protein interactions which affect liposome stability and clearance in vivo. PMID- 1751530 TI - Investigation of a possible correlation between rates of secretion and microsomal membrane association of plasma proteins synthesized by rat liver. AB - The rates of secretion of complement C3, haptoglobin and plasminogen have been determined after pulse labelling with [3H]leucine, and compared to the secretion of prothrombin, albumin and transferrin investigated previously (Kvalvaag, A.H., Tollersrud, O.K. and Helgeland, L. (1988) Biochim. Biophys. Acta 937, 319-327). To study membrane association, rough microsomes were treated with increasing concentrations of saponin, sodium deoxycholate or Triton X-100. All six proteins were quantitated in the soluble and membrane fraction by enzyme immunoassays. At concentrations of saponin from 0.08% to 0.32%, each secretory protein showed a characteristic distribution, almost identical to that obtained with 0.05% sodium deoxycholate or 0.08% Triton X-100. Albumin and transferrin with half-times for secretion (t1/2) 30 and 75 min, respectively, are both almost exclusively found in the luminal fraction (greater than 95%). Prothrombin and plasminogen, which both show an intermediate t1/2 (approx. 55 min), are partially associated with the membranes, as only about 60% was released. Haptoglobin and complement C3 also show some association with the membranes (80-85% released). C3 is secreted at the same rate as prothrombin and plasminogen (t1/2 = 55 min), whereas haptoglobin is secreted more rapidly (t1/2 = 40 min). Accordingly, no correlation between kinetics of secretion and membrane association was demonstrated. PMID- 1751531 TI - Lipid and membrane fluidity abnormalities in platelets and megakaryocytes of the hereditary macrothrombocytopenic Wistar Furth rat. AB - Biochemical and functional abnormalities of megakaryocytes and platelets were studied in Wistar Furth (WF) rats which have genetically determined macrothrombocytopenia and megakaryocytopenia, and were compared with their counterparts in Sprague-Dawley (SD) rats. Both megakaryocytes and platelets synthesized phospholipids from [14C]acetate. WF and SD megakaryocytes incorporated 0.27 and 0.29 nmol acetate per 10(6) cells, respectively. Phosphatidylcholine (PC) accounted for 64% and 58% of the PL radioactive label in megakaryocytes of SD and WF rats, respectively, (P less than 0.05), while 69% of labeled activity was associated with PC of SD platelets compared to 60% found in PC of WF platelets (P less than 0.01). In WF platelets a significant increase in the levels of lysophosphatidylcholine (6.1% vs. 3.0%) was observed. WF platelets had substantially higher levels of esterified cholesterol, triglycerides, ceramides and a 3-fold increase in the total protein per platelet compared to SD platelets. The fatty acid composition of WF platelet PC showed quantitative abnormalities. Plasma lecithin-cholesterol acyl transferase activity and platelet function monitored by the uptake and release of [14C] serotonin showed nonsignificant variations between SD and WF rats. Compared with the control, platelet membrane fluidity, measured by fluorescence polarization using platelets labeled with 1,6-diphenyl-1,3,5-hexatriene, was significantly decreased in the WF rats. PMID- 1751532 TI - Interactions of an antimicrobial peptide, tachyplesin I, with lipid membranes. AB - Tachyplesin I, isolated from the acid extracts of hemocytes of Tachypleus tridentatus, is a cyclic broad-spectrum antimicrobial peptide forming a rigid, antiparallel beta-sheet because of two intramolecular S-S linkages. The strong binding of the peptide to lipopolysaccharides cannot explain the susceptibilities of gram positive bacteria and fungi to the peptide. We found that tachyplesin I caused a rapid K+ efflux from Escherichia coli cells, concomitant with a reduced cell viability. This result suggests that the peptide-induced permeability enhancement of the bacterial membranes may be a plausible action mechanism. Thus, we studied the interactions of tachyplesin I with various large unilamellar vesicles (LUVs) to reveal the molecular machinery of the antimicrobial activity. Tachyplesin I induced the leakage of calcein, a trapped fluorescent marker, from LUVs of acidic phospholipids, especially phosphatidylglycerol (PG), but not from phosphatidylcholine LUVs. A detailed analysis found that the affinity of the peptide to the PG membranes is very strong and that the binding of one peptide molecule to approx. 200 lipid molecules leads to a significant leakage. The location of tachyplesin I in membranes was estimated by use of the Trp-2 fluorescence of the peptide. The presence of PG LUVs caused a blue shift of the maximum wavelength, an increase in the quantum yield, and a complete protection from fluorescence quenching by an aqueous quencher, acrylamide. Moreover, the degree of fluorescence quenching of the Trp residue by n-doxylstearates was in the order n = 5 greater than 7 greater than 12 approximately equal to 16. These results show that the Trp residue of tachyplesin I seems to locate in a hydrophobic environment near the surface of the PG bilayers. PMID- 1751533 TI - The cesium-induced delay in myoblast membrane fusion is accompanied by changes in cellular subfraction lipid composition. AB - We have recently demonstrated that the delay in myoblast membrane fusion induced by cesium is accompanied by changes in isolated membrane lipids (Santini, M.T., Indovina, P.L., Cantafora, A. and Blotta, I. (1990) Biochim. Biophys. Acta 1023, 298-304). In the present study, we have investigated changes in the lipid profile of total cell homogenates and microsomal membrane fractions during myoblast membrane fusion as well as the effects that addition of cesium may have on these lipid variations in order to try to understand the production and translocation of lipids during this myogenic process. The data presented here indicate that the lipid composition of cell homogenates and microsomes varies in a different manner from isolated plasma membranes during myogenic fusion. In addition, cesium affects, in a different manner, the normally-occurring lipid production and distribution which takes place in each subcellular fraction. PMID- 1751534 TI - Accumulation of polyunsaturated free fatty acids coincident with the fusion of rough endoplasmic reticulum membranes. AB - The accumulation of polyunsaturated free fatty acids (PUFAs) was observed coincident with GTP-dependent fusion of liver rough microsomes. Whereas 0.5 mM NADPH led to a parallel reduction (greater than 50%) in membrane fusion and PUFA accumulation, indomethacin (50 microM) either had little effect or slightly augmented both processes. CTP was observed to stimulate accumulation of PUFAs and diacylglycerol (DAG). Therefore PUFAs may be relevant for GTP-dependent membrane fusion and together with DAG may play a role in fusion stimulated in the presence of CTP. PMID- 1751535 TI - Measurements of local pH changes near bilayer lipid membrane by means of a pH microelectrode and a protonophore-dependent membrane potential. Comparison of the methods. AB - Shifts of pH near the bilayer lipid membrane (BLM) were measured in the absence of pH difference between bulk solutions by two methods, i.e. pH microelectrode and membrane potential recordings in the presence of a protonophore. A quantitative agreement of the results of both methods was obtained. The kinetics of the generation of potential induced by the addition of ammonium chloride was accounted for by the time of the diffusion through the unstirred layers. The thickness of the unstirred BLM layers was determined in the experiment. PMID- 1751536 TI - The effect of monoacylglycerol on the phase behavior of egg phosphatidylcholine. AB - Phosphatidylcholine bilayers can accommodate large quantities of monoacylglycerol. Incorporating up to 40% monoacylglycerol has little effect on the orientation and motion of the phosphatidylcholine polar group. Briefly heating mixed dispersions of 1-monooleoylglycerol/egg phosphatidylcholine (1:1, weight ratio; 2.1:1, mole ratio) to 50-60 degrees C induced spontaneous vesiculation: unilamellar and some oligolamellar vesicles bud off the large multilamellar particles. The size of the resulting vesicles ranges from 100 to 1000 nm, with the bulk of the vesicles having diameters between 100 and 500 nm. The spontaneous vesiculation process is reflected in the visual clearance of the mixed lipid dispersion and in the collapse of the 31P powder NMR spectrum to a sharp, asymmetric peak. The narrowing of the 31P-NMR spectrum is explained in terms of additional molecular and/or segmental motion of the lipid polar groups. In mixed dispersions of 1-monooleoylglycerol/egg phosphatidylcholine containing an excess of 1-monooleoylglycerol (greater than or equal to 50%) domain formation takes place, i.e., the formation of local clusters enriched in either of the two lipids. As a result the mechanical properties of these mixed lipid bilayers seem to be quite different from those of pure egg phosphatidylcholine. PMID- 1751537 TI - Capsaicin effects on non-neuronal plasma membranes. AB - Capsaicin has been touted as a pharmacological tool specific for sensory afferent neurons and is widely used in neurophysiological studies. However, we have recently demonstrated that in concentrations commonly employed within the gastrointestinal tract, capsaicin inhibits platelet aggregation to at least three different stimuli. Since this was observed in a nerve free system it raised the question of how specific capsaicin is. In this communication we report that capsaicin has profound effects on physical properties of non-neuronal cell plasma membranes. These effects were observed while measuring the effect of capsaicin upon the fluidity of both intact cell membranes and a variety of purified membrane preparations. Membrane fluidity was assessed with the fluorescent probes diphenylhexatriene (DPH) and its trimethylamino derivative TMA-DPH and demonstrated concentration-dependent capsaicin effects. Furthermore, the effects were cell specific and for full expression required both intact cells and a non lipid extractable component of the plasma membrane. These non-neuronal effects must be carefully considered when contemplating the explanation for capsaicin induced effects. PMID- 1751538 TI - Anomalous mixing of zwitterionic and anionic phospholipids with double-chain cationic amphiphiles in lipid bilayers. AB - High-sensitivity scanning calorimetry has been used to examine the thermotropic behavior of mixtures combining dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (DPPE) and O-methylphosphatidic acid (DPPA-OMe) with the double-chain cationic amphiphiles N,N-dihexadecyl-N,N- dimethylammonium chloride (DHDAC), 1,2-dipalmitoyloxy-3-(trimethylammonio)propane (DPTAP) and the corresponding monomethylated tertiary amino compounds (DHMMA-H+ and DPDAP-H+). At physiological ionic strength, mixtures of these cationic amphiphiles with the anionic phospholipid DPPA-OMe can show gel-to-liquid-crystalline phase transitions at considerably higher temperatures than do either of the pure components. Surprisingly, binary mixtures of DPPC and these cationic amphiphiles also show strongly nonideal mixing, with phase diagrams exhibiting pronounced maxima in their solidus and liquidus curves. Similar behavior is not observed for mixtures of DPPC with DPPA-OMe, which closely resembles DPTAP and DPDAP-H+ in backbone configuration and polar headgroup size. The present results suggest that perturbation of the orientation of the phosphatidylcholine headgroup by cationic amphiphiles, as demonstrated previously by Seelig and co-workers (Biochemistry 28 [1989], 7720-7728), can significantly affect the thermotropic behavior of phospholipids such as DPPC. Such effects may exert a generally important (though not always easily recognizable) influence on the organization and thermotropic behavior of systems where zwitterionic phospholipids are combined with charged bilayer-associated molecules. PMID- 1751539 TI - Plasma membrane depolarization and calcium influx during cell injury by photodynamic action. AB - The plasma membrane has been implicated as one of the critical targets of photodynamic action. We observed that plasma membrane depolarization is an early event in the photodynamic action of zinc phthalocyanine disulfonate in mouse myeloma cells, showing both photosensitizer concentration and light dose dependence. The depolarization was observed immediately upon exposure to light, while membrane integrity was retained and showed a strong correlation with cell killing. In this study the use of channel blockers and alteration of ion concentration was employed to determine the factors involved in the membrane depolarization process. A general rise in cation permeability is associated with the depolarization. Loss of intracellular potassium was detected and an increase in intracellular free calcium was also observed. Sodium was found to strongly influence the photosensitized depolarization. PMID- 1751540 TI - Inhibition of L-lactate transport and band 3-mediated anion transport in erythrocytes by the novel stilbenedisulphonate N,N,N',N'-tetrabenzyl-4,4' diaminostilbene-2,2'-disulpho nat e (TBenzDS). AB - (1) The synthesis of the novel stilbenedisulphonate N,N,N',N'-tetrabenzyl- 4,4' diaminostilbene-2,2'-disulphonate (TBenzDS) is described, and its interaction with the lactate transporter and band 3 protein of erythrocytes investigated. At 10% haematocrit the IC50 (concn. required for 50% inhibition) for inhibition of transport of 0.5 mM L-lactate into rat erythrocytes at 7 degrees C was approx. 1.6 microM, as low as any other inhibitor of the transporter. In human erythrocytes at 10% haematocrit the IC50 value was increased from approx. 3 microM to 9 microM upon raising the temperature from 7 degrees C to 25 degrees C. (2) TBenzDS inhibited transport of L-lactate into rat erythrocytes in a manner that was competitive with the substrate, as is the case for some other stilbene disulphonate derivatives (Poole, R.C. and Halestrap, A.P. (1991) Biochem. J. 275, 307-312). (3) Increasing the haematocrit from 5 to 20% caused a 3-fold increase in the IC50 value for inhibition of L-lactate transport in rat erythrocytes. (4) TBenzDS was found to bind to erythrocyte membranes, with a partition coefficient (Pm) of 6000-7000 under all conditions tested. (5) TBenzDS also inhibited band 3 mediated sulphate transport in rat erythrocytes; 50% inhibition required approx. 2.5 microM TBenzDS for cells at 10% haematocrit. (6) TBenzDS is fluorescent, and an enhancement of this fluorescence occurs upon addition of BSA or erythrocyte membranes. The fluorescence enhancement caused by erythrocyte membranes is due to binding of the inhibitor to the band 3 protein at the same site as the stilbenedisulphonate 4,4'-diisothiocyanodihydrostilbene-2,2'-disulphonate (H2DIDS). PMID- 1751541 TI - The transport systems of mammalian lysosomes. PMID- 1751542 TI - Techniques and concepts in exocytosis: focus on mast cells. PMID- 1751543 TI - c-myc oncoprotein function. AB - Genetic alterations of the c-myc locus in various malignancies and the ability of c-myc to transform cultured cells and induce tumors in transgenic animals attest to its central role in many neoplasms. By dissecting the c-Myc protein, a number of critical functional domains of c-Myc have been identified and characterized; these findings suggest a model for c-Myc function and intracellular activity (Fig. 4). c-Myc is synthesized in the cytoplasm and undergoes oligomerization another protein such as Max. Its nuclear localization signal allows c-Myc to be targeted to and retained in the nucleus, where the protein seeks out and binds to specific DNA sites, perhaps facilitated by c-Myc's ability to bind non specifically to DNA. Once bound to specific DNA sequences, c-Myc then activates or inhibits transcription of a number of target genes, with consequent alterations in cell growth and differentiation. Continued studies of c-Myc and its partner Max should further elucidate the mechanisms by which c-Myc can contribute both to the regulation of normal cell growth and the alteration in that regulation in neoplasia. PMID- 1751544 TI - The trk family of tyrosine protein kinase receptors. PMID- 1751545 TI - The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. PMID- 1751546 TI - Molecular mechanisms in lung pathogenesis. PMID- 1751547 TI - Antigen receptor genes in hemopoietic malignancies. PMID- 1751548 TI - Ras p21: effects and regulation. PMID- 1751549 TI - Protection of cellular and mitochondrial functions against anoxic damage by fructose in perfused liver. AB - In anoxic perfused liver, conversion of fructose to lactate was greatly increased to about 3 mumol/min per g liver. This increase in lactate implied that the same amount of ATP was also produced. The rate of metabolism of glucose was less than 10% of that of fructose, as judged by rate of production of lactate. In anoxic liver perfused with fructose, the ATP levels of both the tissue and mitochondria remained high, despite lack of oxygen, thus preventing enzyme leakage and preserving processes requiring ATP, such as bile excretion and urea formation. The mitochondrial oxidative phosphorylation capacity of anoxic liver perfused with fructose was also unimpaired. Spectral analysis of light transmitted through the liver revealed that the mitochondrial electron transfer system was in the completely reduced state during anoxia, indicating that the mitochondria were incapable of synthesizing ATP. These results suggest that fructose metabolism during anoxia resulted in sufficient production of ATP for maintaining the physiological functions of the cells and the oxidative phosphorylation capacity of their mitochondria. PMID- 1751550 TI - On the thyroid hormone-induced increase in respiratory capacity of isolated rat hepatocytes. AB - The respiratory capacities of hepatocytes, derived from hypothyroid, euthyroid and hyperthyroid rats, have been compared by measuring rates of oxygen uptake and by titrating components of the respiratory chain with specific inhibitors. Thyroid hormone increased the maximal rate of substrate-stimulated respiration and also increased the degree of ionophore-stimulated oxygen uptake. In titration experiments, similar concentrations of oligomycin or antimycin were required for maximal inhibition of respiration regardless of thyroid state, suggesting that the changes in respiratory capacity were not the result of variation in the amounts of ATP synthase or cytochrome b. However, less rotenone was required for maximal inhibition of respiration in the hypothyroid state than in cells from euthyroid or hyperthyroid rats, implying that hepatocytes from hypothyroid animals contain less NADH dehydrogenase. The concentration of carboxyatractyloside necessary for maximal inhibition of respiration was 100 microM in hepatocytes from hypothyroid rats, but 200 microM and 300 microM in hepatocytes from euthyroid and hyperthyroid rats, respectively, indicating a possible correlation between levels of thyroid hormone and the amount or activity of adenine nucleotide translocase. The increased capacity for coupled respiration in response to thyroid hormone is not associated with an increase in the components of the electron transport chain or ATP synthase, but correlates with an increased activity of adenine nucleotide translocase. PMID- 1751551 TI - Adaptation of Bacillus FTU and Escherichia coli to alkaline conditions: the Na(+) motive respiration. AB - Mechanisms of Na+ transport into the inside-out subcellular vesicles of alkalo- and halotolerant Bacillus FTU and of Escherichia coli grown at different pH have been studied. Both microorganisms growing at pH 7.5 are shown to possess a system of the respiration-dependent Na+ transport which (i) is inhibited by protonophorous uncoupler, by delta pH-discharging agent diethylammonium (DEA) acetate, by micromolar cyanide arresting the H(+)-motive respiratory chain, and by amiloride, and (ii) is resistant to the Na+/H+ antiporter monensin and to Ag+, inhibitor of the Na(+)-motive respiratory chain. Growth at pH 8.6 strongly changes the activator and inhibitor pattern. Now (1) protonophore stimulates the Na+ transport, (2) DEA acetate is without effect in the absence of protonophore and is stimulating in its presence, (3) amiloride and low cyanide are ineffective, (4) monensin and Ag+ completely arrest the Na+ accumulation in the vesicles. Independent of pH of the growth medium, (a) valinomycin is stimulatory for the Na+ transport, (b) Na+ ionophore ETH 157 is inhibitory and, (c) Na+ transport can be supported by NADH----fumarate as well as by ascorbate (TMPD)--- O2 electron transfers. Growth at alkaline pH results in the appearance of ascorbate (TMPD) oxidation resistant to low and sensitive to high cyanide concentrations. These relationships are in agreement with the concept (Skulachev, V.P. (1984) Trends Biochem. Sci. 9, 483-485) that adaptation to alkaline conditions in bacteria growing in the high [Na+] media causes substitution of Na+ for H+ as a coupling ion. The obtained data indicate that under alkaline conditions, Na+ can be pumped from the cell by the Na(+)-motive respiratory chain with neither H(+)-motive respiration nor the Na+/H+ antiporter involved. In the Na(+)-motive respiratory chain of Bac. FTU or E. coli, two Na+ pumps are localized, one in its initial and the other in its terminal spans. PMID- 1751552 TI - Molecular mechanisms for the control of enzymic activity by protein phosphorylation. PMID- 1751553 TI - The administration of triiodothyronine to rats results in a lowering of the mitochondrial membrane potential in isolated hepatocytes. AB - Although thyroid status has been shown to influence the magnitude of the membrane potential in isolated rat-liver mitochondria, there is variation in the reported size and direction of the thyroid hormone-induced change relative to the normal state. Measurement of the mitochondrial membrane potential in intact hepatocytes isolated from hyperthyroid and euthyroid rats reveals that hyperthyroidism results in a decrease of approximately 30 mV in the magnitude of this potential relative to that in the euthyroid state. As well, the magnitude of the plasma membrane potential of hepatocytes from hyperthyroid rats is reduced by 6 mV compared with that in cells from euthyroid rats. The thyroid hormone-induced decrease in these potentials may reflect reported changes in the lipid composition of the membranes. PMID- 1751554 TI - Secretion of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from cultured chick embryo chondrocytes. AB - We found that chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase were released into the culture medium from the cultured chick embryo chondrocytes. Since the release of the sulfotransferases was observed not only in serum-supplemented medium but also in serum-free medium, the released sulfotransferases were unlikely to be derived from serum. Addition of ascorbate to the serum-free medium supported the continuous release of the sulfotransferases. Monensin, which is known to cause dilatation of the Golgi apparatus and to inhibit sulfation of proteoglycan, was found to affect the release of the sulfotransferases. In the presence of 10(-6) M monensin, chondroitin 6-sulfotransferase activity in the cell layer was decreased to less than one tenth of the control, and the rate of the release of the activity became much smaller than the control after the initial rapid release. The activity of chondroitin 4-sulfotransferase was also affected by monensin, but the reduction of the chondroitin 4-sulfotransferase activity in the cell layer was not so great as the reduction of chondroitin 6-sulfotransferase activity. Unlike to the microsomal sulfotransferases, both chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase released into the culture medium were retained in the soluble fraction after centrifugation at 100,000 x g for 60 min, and were not activated by detergent. pH optimum and requirements for sulfhydryl compounds of the released sulfotransferases were similar to those observed previously in the chondroitin sulfotransferases from chick embryo cartilage and from cultured chick embryo chondrocytes. These results suggest that chondroitin sulfotransferases, which are localized in the Golgi apparatus, may be secreted to the extracellular space in a soluble form under the culture conditions. PMID- 1751555 TI - [Radiologic diagnosis in hyperparathyroidism]. AB - The most important radiologically detectable effects of the primary and secondary hyperparathyroidism of the skeletal system and the periarticular soft tissue structures are presented. In the following sensitivity and specificity of radiological imaging--sonography, scintigraphy, computed tomography, magnetic resonance imaging, arteriography and selective venous sampling--in the preoperative diagnostic of the parathyroid adenomas are discussed. Therefore, radiological imaging can be omitted before primary surgery. It was only in secondary surgery that radiological process proved useful and a guide during surgical intervention. PMID- 1751556 TI - [Quality control of film viewing boxes]. AB - Film inspection boxes have been examined in order to find out whether the introduction of the Roentgen regulation has led to positive results with regard to amount, illuminating density and homogeneity. In comparison to former results which have been published, it seems that the illuminating density is still too low. On the average, we found a value of 1.700 cd/m2. PMID- 1751557 TI - [Introductory remarks of the Editor to the comments on the paper "The visual method for constancy testing of film processing" by H. Eder]. PMID- 1751558 TI - [Color-coded Doppler sonography of chronic venous insufficiency]. AB - 20 patients (i.e. 40 lower extremities) with chronic venous insufficiency were examined by means of colour-coded Doppler sonography (CCDS). This method enables the simultaneous visualisation of the anatomy and haemodynamics of the examined vessels. All cases of varicosis of the stem of the vena saphena magna (VSM) (n = 21) and of the vena saphena parva (VSP) (n = 13) were correctly diagnosed by CCDS. However, an incomplete varicosis of the stem was identified in only 3 of 5 cases. Insufficiency of the V. perforantes was identified by CCDS with a high rate of accuracy in diagnosing the insufficiency of the cross of the VSM and VSP. Although assessment of the V. perforantes and diagnosis of incomplete stem varicoses or varicoses of lateral branches is possible, as a rule, it does take up much time and requires a great deal of experience on the part of the investigator. PMID- 1751559 TI - [The value of plain x-ray diagnosis and phlebography in the thoracic outlet syndrome]. AB - The compression of the neurovascular bundle of the upper limb (thoracic outlet syndrome, TOS) can be caused by osseous, muscular, fibrous, tumourous and habitual abnormalities of the cervicothoracic junction. Osseous causes can be shown in a conventional x-ray of the cervicothoracic junction. In about 40% of the cases there is a venous stenosis which can be proved by means of phlebography in a special patient position (provocation position). The type of stenosis and location provides information on the cause of it. We examined 34 patients. PMID- 1751560 TI - [Complications of pulmonary involvement in Bechterew's disease]. AB - Fibrocystic changes in the upper lung lobes are a rare visceral manifestation of ankylosing spondylitis. The impaired bronchopulmonary clearance in bronchial, pulmonary or pleural cavities predisposes to secondary microbial colonisation. Two cases are reported--one patient proved to have non-tuberculous mycobacterial disease caused by M. kansasii, the other developed an aspergilloma. PMID- 1751561 TI - [The application of digital subtraction angiography in patients with peripheral arterial insufficiency and suspicion of stenosis/occlusion of the superficial femoral artery: intravenous or intra-arterial?]. AB - 36 patients with clinical signs of lower limb ischaemia and suspected stenosis/occlusion of the superficial femoral artery were investigated prospectively and randomly by either intravenous (i.v.) or intraarterial (i.a.) digital subtraction angiography (DSA) to evaluate which of the two modalities might be chosen as a routine examination. In 4 patients from the i.v. group a supplementary i.a. examination had to be performed due to insufficient visualisation of the crural arteries, caused by long occlusions of the femoropopliteal segment. PMID- 1751562 TI - [Iotrolan-300 versus Iopamidol-300 in hysterosalpingography]. AB - From 9.1988 to 7.1989 we carried out on 50 patients at the Department of Gynaecology of the University of Freiburg a randomized double-blind study to compare the first dimeric, nonionic, hexaiodinated, water-soluble contrast agent (Iotrolan-300 corresponding to Isovist-300) with a nonionic, monomeric preparation (Iopamidol-300 corresponding to Solutrast-300) using the concentration of 300 mg I/ml. Both medicaments show a high contrast quality in the X-rays. Complications like hypersensitivity reactions resp. actual local irritations were not recorded. Iotrolan-300 was found to be the best tolerated of the two contrast media in respect of mildest intensity of pain. PMID- 1751563 TI - [A rare constellation of findings: bile duct cancer, ulcerative colitis, deep venous thrombosis of the leg]. AB - A case of a 28-year-old patient with long-standing chronic ulcerative colitis is presented, in whom cholangiocarcinoma was diagnosed by CT and ultrasound guided liver biopsy. This association is well known, because the incidence of bile duct carcinoma in patients with chronic ulcerative colitis is increased. A possible precursor of the disease is thought to be primary sclerosing cholangitis which also more frequently occurs in patients with ulcerative colitis. Our patient was initially hospitalized for deep venous thrombosis, which in retrospect had to be interpreted as a paraneoplastic syndrome. PMID- 1751564 TI - [Empyema necessitatis--a differential diagnostic problem in ventilated patients in intensive care]. AB - Development of an empyema necessitatis under mechanical artificial respiration with high peak pressures is described on the basis of a case report on a patient in whom the phenomenon was the sequel of pneumonia with abscess formation. Conventional x-ray diagnosis can merely yield pointers towards possible differential diagnoses, whereas CT supplies an unequivocal diagnosis. X-ray image and differential diagnosis are discussed. PMID- 1751565 TI - [Traumatic apophyseolysis of the ischiadic tuber]. AB - Traumatic apophyseolysis of the os ischii is a rare injury occurring during sports activities. It mostly affects young men between 14 and 25 years of age. Conservative treatment is often sufficient unless there is a mechanical obstruction or an irritation of the conditioned rupture of the os ischii with subsequent load-dependent complaints. PMID- 1751566 TI - [Aneurysmal bone cyst of the thoracic spine]. AB - A case of aneurysmal bone cyst of the thoracic spine is described. The value of the various imaging procedures in diagnosis of this benign bone lesion and its pathogenesis are discussed. PMID- 1751567 TI - [Global cost analysis of radiological procedures]. AB - In the Federal Republic of Germany, the amount spent on investments in electromedical equipment and systems has remained constant at 0.7% of total health expenditure over the last 15 years. One-fifth of this sum is used for large medico-technical systems such as CT scanners, cardioangiography systems or shock-wave lithotriptors. Expenditure on this category of equipment, including investments and total application costs, amounts to 2 billion DM. This sum also amounts to 0.7% of total health expenditure, or 1.5% of the volume of the statutory health insurance schemes. This paper contains evaluation from various countries showing that the correct implementation of such high-performance units in diagnosis and therapy results in considerable savings. The cost-reducing effects can nevertheless be over-compensated by additional applications carried out due to the specific advantages of these technologies. However, the growing utilisation indicates improved and more economic medical care of the population. PMID- 1751568 TI - [Magnetic resonance tomography. Strong praise for a weak field]. PMID- 1751569 TI - Nurse anesthesia: the practice of nursing, medicine, or something else? PMID- 1751570 TI - Point: MSN is the appropriate academic credential for nurse anesthetists. PMID- 1751571 TI - Counterpoint: MSN is the appropriate academic credential for nurse anesthetists. PMID- 1751572 TI - The morbidity and mortality conference: a prolegomenon on its role as an anesthesia risk-management tool. AB - Although the morbidity and mortality conference (MMC) is an essential component of any anesthesia risk-management program, it has not undergone systematic analysis. All MMC narratives detailing the proceedings at two university centers from June 1988 to June 1990 were examined by content analysis and the unique perspectives of MMC participants were captured. The majority of MMC events were of an educational or informational nature; 32% dealt with patient complications, and 14% involved incidents that could have led to detrimental outcomes. Participant beliefs were ultimately organized into categories describing "the lived experience" of the MMC. These included (1) disclosure of knowledge, (2) correspondence of relationship, (3) teaching conformity to rule, (4) developing a sense of aplomb, (5) preparation for litigation, (6) the ceremony, (7) a quality assurance mechanism, (8) a personal lambaste function, and (9) an instrument of punitive retribution. The MMC appeared improperly named; "case conference" or "clinical teaching conference" may serve as a more accurate rubric. The MMC played a variety of cognitive and affective roles. Recognition of the nature of the teaching and learning associated with the MMC will allow risk managers to utilize it optimally in achieving envisioned objectives that enhance patient outcomes. PMID- 1751573 TI - Comparison of two instructional methods on the levels of physiologic and psychologic stress as measured by blood cortisol and the State-Trait Anxiety Inventory. AB - This study was designed to determine whether a systematic or nonsystematic instructional strategy affected the levels of physiologic and psychologic stress as measured by blood cortisol levels and the State-Trait Anxiety Inventory (STAI) in students in the postsecondary educational setting. A convenience sample consisting of 43 subjects was randomly assigned to either a systematic or nonsystematic teaching group. The blood cortisol and STAI were measured 1 and 2 weeks before the treatment and following the treatment on the day of the study. Results of the study demonstrated that there were differential posttreatment increases in the amount of physiologic stress, as measured by blood cortisol levels produced by either instructional method. However, between the control measurement 1 week before the treatment and the posttreatment measurement, there were no effects observed for the psychologic STAI measures for either group. Accounting for the circadian rhythm effect of cortisol, there was a significant "buffering effect" in stress experienced by the subjects in the systematic teaching group. More specifically, the nonsystematic teaching group experienced a 55.42% rate increase in cortisol compared to a 10.74% rate increase for the systematic teaching group which was statistically significant. The systematic teaching method may be more effective in preventing physiologic stress in the educational setting and possibly in the clinical practice of anesthesia nursing. Additionally, the results suggested that the STAI may be inappropriate when used as an index of stress in certain educational settings. PMID- 1751575 TI - Writing a case report for the literature. PMID- 1751574 TI - Impact of whole blood usage in massive transfusion. AB - A retrospective survey comparing blood and component usage during thoracoabdominal aortic reconstruction between patients receiving whole blood vs packed red cells was conducted. Volume of salvaged blood, usage of homologous blood components, and total homologous exposures were compared between eight patients who received only packed red blood cells and four patients who received whole blood for replacement of surgical losses, using a chi-square test for comparison. All variables demonstrated a decline among patients who received whole blood. The declines in homologous blood and plasma usage were statistically significant (P less than .05). The decline in platelet usage did not reach statistical significance. The decline in total homologous exposures approached statistical significance (P less than .1). The data suggest that use of whole blood for expected massive transfusion may reduce total blood-component requirements and total homologous exposures. PMID- 1751576 TI - Newsletters respond to AIDS and cancer information overload. PMID- 1751577 TI - Treatment of non-Hodgkin's lymphoma. AB - Many of the advances in the management of non-Hodgkin's lymphomas have been based on more precise understanding of the various cell types that constitute these disorders. During the past year, we have seen some dramatic changes in the therapeutic approach to low-grade lymphomas. Until recently, the usual approach to these disorders was a purely palliative one, but a number of publications from the past year describe a more intensive approach with the goal of developing a curative modality. The use of combination chemotherapy in addition to radiation therapy for the early Ann Arbor stages as well as the use of high-dose chemotherapy with bone marrow transplantation in patients with high-risk factors has been reported recently. In the area of intermediate-grade lymphomas, most of the recent publications have described prognostic factors associated with various chemotherapy protocols. One of the most interesting recent developments is related to the dose-intensity issue. A consensus appears to be developing in regard to the correlation of dose intensity with clinical outcome. Despite the fact that new third-generation regimens have been associated with cures in 50% to 66% of the patients, a significant fraction of patients require salvage chemotherapy. Some of the new salvage regimens are discussed, as is the use of calcium channel blockers to reverse multiple-drug resistance. Finally, management of the high-grade lymphomas, specifically the small noncleaved cell type, has been associated with a cure rate in the range of 50% in two recently published studies. Patients who are human immunodeficiency virus-positive with small noncleaved cell lymphoma can be cured of their underlying malignancy, but many of them later develop complications of acquired immunodeficiency syndrome, to which they usually succumb. PMID- 1751578 TI - Prognostic factors in Hodgkin's and non-Hodgkin's lymphomas. AB - A review of prognostic factors described recently in Hodgkin's and non-Hodgkin's lymphomas is presented with some comments on their interest and value for treatment choice and comprehension of the disease. The most important parameters are divided into three categories: 1) age; 2) extent of the tumor, ie, number of nodal or extranodal sites, bulkiness, stage, lactate dehydrogenase level or beta 2-microglobulin level; and 3) host-tumor interaction, ie, performance status, serum albumin level, and erythrocyte sedimentation rate. These initial parameters permit the stratification of lymphoma patients into subgroups with different outcomes in which different therapeutic modalities are tested. PMID- 1751579 TI - Treatment-related morbidity in patients with lymphoma. AB - The evolution of effective therapies for lymphoma has led to cures for many patients. In addition to the acute morbidity associated with cytotoxic therapy, significant delayed treatment-related effects have been identified. Complications include immunologic, cardiovascular, pulmonary, thyroid, and gonadal dysfunction as well as the development of second neoplasms. These complications results from tissue injury caused by the administration of radiation or chemotherapy, persistent immunologic deficits related to the underlying malignancy or its therapy, and complications of surgical staging and splenectomy. Disease or treatment-related immunosuppression and the mutagenic effects of therapy appear to predispose these patients to an increased risk of second cancers. This article reviews data from the recently published literature on these issues. PMID- 1751580 TI - Pathogenesis of HIV-related malignancies. AB - Human immunodeficiency virus (HIV)-1 infection is associated with increased frequency of Kaposi's sarcoma and high-grade B-cell lymphoma. Several other cancers in HIV-1-infected individuals have been reported, although without statistically significant increase in their respective occurrences. Although HIV 1 does not infect either Kaposi's sarcoma-derived spindle cells or B lymphocytes in vivo, viral proteins in vitro have been shown to be mitogenic to both Kaposi's sarcoma-derived spindle cells and B lymphocytes. Furthermore, several cytokines influence directly and indirectly the proliferative differentiation capacity of these cells. These cytokines include interleukin-1, interleukin-4, interleukin-6, and tumor necrosis factor. Many of these cytokines also are regulated by HIV-1 infection of T lymphocytes and monocyte/macrophage. Furthermore, elevated levels of interleukin-1, interleukin-6 and tumor necrosis factor have been observed in patients with HIV-1 infection, particularly in advanced stages, when these tumors often manifest. Thus, it appears that although HIV-1 does not directly transform cells permissive to its infection, viral proteins directly and through regulation of cellular genes exert activities that may lead to the development of Kaposi's sarcoma and B-cell lymphoma. PMID- 1751581 TI - Biologic therapy and immunotherapy for ovarian cancer. AB - Ovarian cancer remains an attractive model for evaluation of biologic and immunologic therapies due to the availability of multiple reagents, the development of preclinical murine models, and the intraperitoneal pattern of clinical disease. Recent studies have focused on conjugated monoclonal antibodies, including radioconjugates, immunotoxins, and bispecific antibodies. Other preclinical and clinical studies have been conducted with recombinant cytokines and adoptive cellular immunotherapy for small-volume residual disease. Dose-limiting clinical toxicities have emerged with many of these approaches in the absence of frequent antitumor responses, and new strategies will be required to develop effective therapies in the future. PMID- 1751582 TI - Epidemiology, etiology, screening, prevention, and diagnosis in female genital cancer. AB - Cancers of the endometrium, ovary, and cervix share certain characteristics. Etiologic factors are generally environmental. Prevention of the three cancers requires further improvement in the efficiency of the available screening methods. Trials to improve survival require more accurate staging and diagnosis, in addition to the identification of more significant prognostic factors that could allow recognition of low- and high-risk groups of patients. PMID- 1751583 TI - Issues in gynecologic radiation oncology. AB - Radiation therapy has a number of established roles in the curative, adjuvant, and palliative management of gynecologic malignancies. Specific indications for use of radiation therapy, concepts of integration of radiation therapy with other modalities, and techniques of radiation therapy, however, continue to evolve. Rather than discuss the use of radiation therapy in specific diseases, this paper reviews recent studies dealing with current issues in gynecologic radiation oncology. PMID- 1751585 TI - Lymphoma. PMID- 1751586 TI - Cancer in AIDS. PMID- 1751584 TI - Chemotherapy and complications in gynecologic cancer. AB - Amelioration of toxicity is of major concern to every physician treating patients suffering from gynecologic cancer. If dose escalation in treatment of ovarian cancer is to be considered, the highest priority should be trying to overcome the toxicities of cisplatin, the cornerstone of chemotherapy. So far, dose limiting side-effects are nephro-, neuro-, and ototoxicity. These toxicities may play an even more important role when doses, higher than conventionally given, are to be considered. At higher doses other toxicities such as myelosuppression may become dose limiting. However, nausea and vomiting, which up until now have been intractable, are the most outspoken acute adverse events suffered by the patients. Development of new antiemetic treatment modalities is therefore noteworthy. PMID- 1751587 TI - Gynecologic cancer. PMID- 1751588 TI - Reflections: of hope and of concern. PMID- 1751589 TI - Positive selectable markers for use with mammalian cells in culture. AB - As more complicated gene expression studies are necessary, the need for multiple positive selection schemes becomes critical. Numerous selectable markers have been described over the last 25 years. A hallmark of the most generally useful markers is easy selection in a wide number of cell types. This paper briefly reviews the spectrum of available selectable markers and describes some of the applications that have been found for these genes, particularly with respect to retrovirus-mediated gene transfer. PMID- 1751590 TI - Gene transfer of adenosine deaminase into primitive human hematopoietic progenitor cells. AB - The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoietic stem cell. We have used a combination of recombinant human interleukins-3 and -6 to stimulate the proliferation of primitive human hematopoietic progenitor cells during a period of co-cultivation with irradiated cells producing high titers of an ADA-transducing retroviral vector packaged in amphotropic particles. In a series of nine experiments, an average of 83% of the clonogenic progenitors (CFU-E and CFU-GM) were found to have acquired the transferred sequence as determined by polymerase chain reaction analysis. In addition, in two experiments, 24-44% of the clonogenic progenitors derived from long-term myeloid cultures 9 weeks post-transduction were found to contain vector sequence. The latter cells are derived from so-called "long-term culture initiating cells" (LTC-IC), which are primitive cells probably related to hematopoietic stem cells. Moreover, the transduced ADA enzyme was found to be expressed in both normal and ADA-deficient erythroid colonies, and in the nonadherent cells of long-term bone marrow culture for at least 2 weeks at levels that approximate the endogenous ADA levels of normal erythroid cells. These results indicate that the ADA coding sequence can efficiently be introduced by retroviral gene transfer into both committed and primitive human hematopoietic progenitor cells, and that this will result in adequate expression of the transduced enzyme in the progeny of committed hematopoietic progenitors. PMID- 1751591 TI - Liability considerations presented by human gene therapy. AB - Through the use of a hypothetical scenario, this article examines the legal liability associated with gene therapy. Basic negligence principles are applied to the factual context of a human gene therapy experiment gone awry, including its prior governmental review and its potential effect on future generations. The federal requirements, while not preempting state law damages claims, do provide a mechanism for achieving some protection from liability. The effect on future generations raises questions about the limits of liability. PMID- 1751592 TI - Regulatory concerns in human gene therapy. AB - Gene therapy in humans is now being undertaken in an investigational setting. Such therapy involves the administration of biological products to human patients. A document entitled, "Points to Consider in Human Somatic Cell Therapy and Gene Therapy" has been prepared by the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA) and is published elsewhere in this issue. This paper provides explanatory material about the CBER regulatory process and the scientific and regulatory basis for the requests for data in that document. PMID- 1751593 TI - Points to consider in human somatic cell therapy and gene therapy (1991). PMID- 1751594 TI - Problems in comparisons of clearances prescriptions in hemodialysis and continuous ambulatory peritoneal dialysis. PMID- 1751595 TI - Which statistical method to use when analyzing the incidence of peritoneal dialysis related infections? PMID- 1751596 TI - Multiple-dose-kinetics of ofloxacin after intraperitoneal application in CAPD patients. AB - Pharmacokinetics of ofloxacin in plasma and peritoneal fluid were studied in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Seven patients without peritonitis received 20 mg ofloxacin added to 2L dialysate i.p. every 6 h for one day only, while 4 patients with acute peritonitis were treated with this same dosage every 4 h for 3 days, then every 6 h for the next 7 days. Ofloxacin concentrations in plasma and dialysate were determined by HPLC. After i.p. drug application there was a rapid elimination of ofloxacin from dialysate, this being significantly faster in patients with peritonitis as compared to those without. Likewise, the total amount lost from the first bag after a 3 h dwell was higher in the peritonitis group (84.7 +/- 1.5%; mean +/- SEM) than in the non peritonitis group (75.6 +/- 2.1%). Twenty-four h after start of ofloxacin treatment, the mean peritoneal fluid concentrations at the end of each exchange studied were all above 3 mg/L. In patients with peritonitis, plasma concentrations of ofloxacin rose to 0.94 +/- 0.05 mg/L after 24 h reaching a Cmax of 1.8 +/- 0.2 mg/L after a tmax of 84 +/- 23 h. Intraperitoneal administration of ofloxacin was well tolerated, and no local or systemic adverse events were observed. Peritonitis episodes that were caused by Staphylococcus epidermidis (3) and by E. coli (1) were cured in all patients. PMID- 1751597 TI - Peritoneal transport kinetics of glucose, urea, and creatinine during infancy and childhood. AB - Peritoneal handling of glucose and metabolites is reported to be higher in young children treated with CAPD than in older children. Reference curves for the standardized peritoneal equilibration test (PET) are not available for younger ages. The present study describes the results of the PET in 19 children (mean age 5.0 years, ranging from 0.3-15) during the first month of CAPD treatment. No age dependency for the handling of glucose, urea, and creatinine could be established when the group was subdivided into 1. children below the age of 3 years, and 2. children above that age. There was, however, a significant correlation between equilibration of creatinine and age, indicating more rapid equilibration at younger ages. PMID- 1751598 TI - Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients. AB - Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered. PMID- 1751599 TI - The role of omentectomy in continuous ambulatory peritoneal dialysis. AB - Long-term survival of the peritoneal catheter is essential for successful CAPD. In our unit, all CAPD catheters are now placed by an open surgical technique, which in some cases has included performing a partial omentectomy. The aim of this study was to assess the influence of omentectomy on CAPD catheter survival. Three hundred consecutive CAPD catheters inserted over a 5-year period were analyzed. Omentectomy was performed in 113 cases (38%). Data relating to a number of potentially significant risk/benefit factors were analyzed using multiple regression analysis (proportional hazards method of Cox). Performing a partial omentectomy at the time of catheter insertion was found to significantly improve CAPD catheter survival (p = 0.0002). PMID- 1751600 TI - Exit-site infection in continuous ambulatory peritoneal dialysis: a review. AB - Although the ability of CAPD to successfully treat end-stage renal disease is now well established, exit-site infection (ESI) remains a serious cause of morbidity. The objective of this article is to review recent advancements relating to ESI pathogenesis and its reduction. Current definitions of ESI are reviewed, as are comparative studies of etiology. Emphasis is placed on the literature identifying Staphylococcus aureus as the primary cause of ESI in CAPD. The article reviews reported rates of ESI and discusses reasons for variations of this complication's reported frequency. The selection of catheters available in CAPD are discussed, as are studies demonstrating the threat of S. aureus to catheter survival. The pathogenesis of exit-site infection related to S. aureus nasal carriage in CAPD is reviewed in light of recent findings indicating the pre-CAPD nasal carrier as the patient at risk for subsequent ESI. Postoperative and long-term care of the catheter patient are reviewed for various literature protocols. Treatment recommendations for choice of agents are discussed. Future research should include a better understanding of the morphology of the CAPD catheter exit-site in humans and the healing process. ESI epidemiological studies should be encouraged in tandem with well-designed, controlled studies on the value of prophylactic treatment. PMID- 1751601 TI - Quality of life of patients on in-center hemodialysis versus continuous ambulatory peritoneal dialysis. AB - This study compared chronic hemodialysis and CAPD patients on several quality of life variables: dietary adherence, self-esteem, hope, wellbeing, marital happiness, perceived control over life, marital status, number of emotional support persons, and participation in social, recreational, and work activities. Statistically significant differences in the quality of life variables due to treatment modality or demographic variables were not found. However, CAPD patients did engage in significantly more social and recreational activity, though not more work activity, than did hemodialysis patients. It is noted that 73% of the CAPD patients were Caucasian and that 72% of the hemodialysis patients were of black origin. Similarly skewed racial compositions in preceding research comparing patients on CAPD and hemodialysis suggest that 1. choice of treatment is occurring on the basis of some set of patient characteristics, or 2. systematic assignment is occurring on the basis of race, sex, and/or education. However, given no significant race/demography differences for variables used in this research, it appears that quality of life across racially different groups of hemodialysis and CAPD patients is comparable. PMID- 1751602 TI - Catheter infections in insulin-dependent diabetics on continuous ambulatory peritoneal dialysis. AB - We compared a group of 60 insulin-dependent diabetics maintained on CAPD with 60 nondiabetic matched controls to determine if the diabetic patients were at increased risk for catheter-related infections. Although catheter infection rates were 17% higher in the diabetics (1.4/year versus 1.2/year in nondiabetics), time to first catheter infection was not different between the groups (p = 0.6). Rates of peritonitis, peritonitis associated with catheter infection, multiple catheter infection, and catheter removal were also similar among the diabetics and controls. S. aureus caused 52% (42/81) of the catheter infections in the diabetics and 60% (35/58) in the controls. More catheter infections in the nondiabetics versus the diabetics lacked drainage or resulted in sterile cultures (17/75 versus 7/88 respectively, p less than or equal to 0.01), but the significance of this finding is uncertain. In conclusion, we did not find insulin dependent diabetes mellitus to be a statistically significant risk factor for catheter-related infections. PMID- 1751603 TI - Effects of chondroitin sulphate on fluid and solute transport during peritoneal dialysis in rats. AB - The effect of chondroitin sulphate (CS) on peritoneal fluid and solute transport was studied in rats undergoing peritoneal dialysis. In the presence of CS, net ultrafiltration increased, while absorption of glucose and horseradish peroxidase from the peritoneal cavity decreased. Albumin, used instead of CS, did not modify either fluid or solute transport. In in vitro experiments on isolated rabbit mesentery, CS decreased transmembrane water flow induced by hydrostatic pressure, and its effect was not fully reversed 60 minutes after "wash-out" of this glycosaminoglycan. We postulate that the polyanionic CS molecules are trapped in the peritoneal interstitium, thus decreasing its hydraulic conductivity and permeability, which in turn increases net fluid removal during peritoneal dialysis because of its slower absorption from the peritoneal cavity. PMID- 1751604 TI - Can intracatheter retention of antifungal agents cure fungal peritonitis? Two cases successfully treated without catheter removal. PMID- 1751605 TI - CAPD in patients unable to do their own bag change. PMID- 1751606 TI - Intraluminal lithiasis of a peritoneal catheter. PMID- 1751607 TI - Recovery of S. epidermidis and E. coli from effluent peritoneal dialysate. PMID- 1751608 TI - Intraperitoneal phosphate for severe hypophosphatemia. PMID- 1751609 TI - An "organizer" for a safe bag exchange. PMID- 1751610 TI - Prazosin induced priapism in a patient on continuous ambulatory peritoneal dialysis (CAPD) PMID- 1751611 TI - Literature. October-December 1991. PMID- 1751612 TI - [The effect of the acidity of the medium on the magnitude of the light-dependent antibacterial activity of chlorophyllides]. AB - The influence of medium acidity on the intensity of light-dependent antibacterial activity of chlorophyllides isolated from biomass of microscopic green alga Westella botryoides has been studied. This light-dependent antibacterial activity has been shown to be maximum at low pH values. The ability to suppress the bacterial growth under the action of light decreases in neutral and alkaline media. It has been concluded that the reason of increase of light-dependent antibacterial activity of chlorophyllides at low pH values is formation of pheophorbides out of them PMID- 1751613 TI - [Microorganisms synthesizing enzymes with thrombolytic action]. AB - The literary and experimental data obtained by the authors concerning the ability of various microorganisms to synthesize exoproteases lysing the thrombi of human blood are presented in the article. Various methods of enhancing the thrombolytic activity of microorganisms cultures, the properties of some isolated and purified preparations, methods of enlarging the specificity of the enzymes to fibrin and of reduction of their toxicity are considered. PMID- 1751614 TI - [The characteristics of the effect of dipalmitoylphosphatidylcholine and its structural fragments on the lipid peroxidation of biological membranes]. AB - The effect of dipalmitoyl phosphatidylcholine (DPPC) and its structural fragments -phosphatidic acid (PA) and choline chloride--on the ascorbate-dependent mice liver microsomal lipid peroxidation (LP) has been studied at the different LP rate. At DPPC, PA and choline chloride introduction into the incubation medium before the onset of peroxidation induction DPPC causes the more considerable inhibition of LP than PA each separate fragment. The inhibition effect of DPPC is lower than PA or choline chloride when DPPC, PA and choline chloride added on the background of developing process of peroxidation (e.i. after LP induction). A specific regulatory role of PC in the normal cell membrane LP process and during pathologic development is under discussion. PMID- 1751615 TI - [The effect of arginine on cytochrome P-450 activity and the structural state of the microsomal membranes of the rat liver and testes]. AB - A single intraperitoneal arginine injection increases the amidopyrin demethylation on 230% and aniline hydroxylation on 74% in rat liver microsomes. For all this the rate of lipid peroxidation estimated by the number of dienic conjugates and Schiff bases does not change. At the same time the exogenous arginine decreases the lipid bilayer microviscosity on 35% and increases the degree of protein submersion into lipid matrix on 54%. The experiments in vitro confirm the fact of activation in cytochrome P-450 isoform by arginine. A possible arginine effect on microsome membrane is under discussion. PMID- 1751616 TI - [The modifying effect of novocaine on the clinical manifestations of the intestinal form of radiation sickness]. AB - On rats and dogs exposed to absolute lethal doses of X-irradiation (rats--10, 12 Gy; dogs--15 Gy sublethally) it has been shown that novocaini injection to animals immediately after radiation exposure reduces the primary radiation reaction and at the same time shifts the changes in morphofunctional state of peripheric blood on 24 hours, reduces the symptoms of acute radiation sickness, increases the average life length of the animals on 1,5 days. A conclusion concerning the expressed therapeutic influence of intraperitoneal novocaini injection immediately after radiation has been drawn. PMID- 1751617 TI - [The effect of the acute and chronic administration of dalargin to mongrel rats on cardiac chronotropism at rest and under physical loading]. AB - In chronic experiments on untrained awakening males of white rats it has been shown that the prolonged intraperitoneal injection of the opiate receptor agonist delargin (during 4, 5 days; 10 mkg/kg; twice a day) leads the chronotropic heart response to the maximum level of exercises and simultaneous decrease of heart rate variability. All this is accompanied by animals' undue fatiguability. It has been concluded that the chronic injection of opioid agonist receptors causes the decrease of sensitivity of these receptors to the action of endogenic opioids and as a consequence--the increase of sympathetic regulatory action on the heart rate at physical exercises and growth of fatiguability. PMID- 1751618 TI - Chronic fatigue syndrome: the need for an integrative approach. PMID- 1751619 TI - Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction. AB - This study was designed to investigate whether auditory P300 event-related potential and smooth pursuit eye-movement abnormalities in schizophrenia are associated with brain structural changes measured using magnetic resonance imaging (MRI). Serial coronal MRI scans obtained from 31 schizophrenic subjects and 33 volunteer controls were analysed by a rater who had no knowledge of the subjects' diagnoses. The brain areas measured bilaterally were the temporal lobe, hippocampus, amygdala, parahippocampal gyrus, head of caudate, cingulate cortex, frontal cortex, and the lateral ventricles. The area of the third ventricle, the thickness of the corpus callosum, and the intracranial area were also measured. Auditory P300 and eye tracking performance were recorded on all subjects. There was a significant increase in the latency and a reduction in amplitude of the P300 in the schizophrenic group. Only in the schizophrenic group was P300 latency correlated negatively with the area of the right and left cingulate cortex and positively with the difference in size between the right and left amygdala. In the subgroup of schizophrenic subjects whose P300 latency was greater than 2 standard deviations above the control mean, the area of the left cingulate cortex was significantly smaller than in controls, and the absolute right-left difference in the area of the amygdala was significantly increased. Eye tracking dysfunction in schizophrenia was not related to changes in the amygdala or cingulate cortex but was significantly correlated with enlargement of the lateral ventricles. Schizophrenic subjects with poor eye tracking had significantly larger lateral ventricles than controls. Eye tracking dysfunction, but not P300 abnormality, was correlated with the severity of both positive and negative symptom of schizophrenia. These findings demonstrate that psychophysiological abnormalities are associated with altered brain structure in schizophrenia. PMID- 1751620 TI - The MCPP challenge test in schizophrenia: hormonal and behavioral responses. AB - In a neuroendocrine challenge paradigm, the present study investigated responses of schizophrenic patients to m-chlorophenylpiperazine (MCPP), a serotonin (5 hydroxytryptamine, 5HT) agonist. In an oral dose of 0.25 mg/kg, MCPP was administered in a placebo-controlled double-blind design to male schizophrenic patients (n = 7) and normal male controls (n = 8). Behavioral (Positive and Negative Syndrome Scale; PANSS) and hormonal (cortisol, prolactin) variables were measured over the subsequent 210 min. The schizophrenic patients experienced an overall exacerbation of psychopathology on MCPP as compared with placebo (p less than 0.05), with specific worsening of PANSS-positive symptoms (p less than 0.025) and PANSS activation (p less than 0.001). In addition, the schizophrenic patients showed significantly lower cortisol (p less than 0.05) and prolactin (p less than 0.05) responses than the normal subjects. The schizophrenic patients had lower peak MCPP blood levels than the normal subjects, although this difference was not statistically significant. The findings are discussed in terms of 5HT receptor(s) sensitivity and the pharmacokinetics of MCPP in schizophrenia. PMID- 1751621 TI - Maladaptive anticipatory saccades in schizophrenia. AB - We compared the saccades made by 8 neuroleptic-treated and 7 drug-free schizophrenic inpatients with those made by 11 normal controls during two eye movement tasks. The first task was designed to elicit visually guided but not internally guided saccades. The second task was designed so that optimal performance required saccades be guided on the basis of an internal representation of target behavior. During the first task, schizophrenics made visually guided saccades that were as accurate as those made by control, but both drug-free and neuroleptic-treated schizophrenics made intrusive saccades at a significantly higher rate than control subjects. Most of these maladaptive saccades appeared to be premature attempts to anticipate target jump. During the second eye movement task, which for optimal performance required use of an internal representation to guide eye movements, most patients learned to anticipate target jump as well as controls. However, neuroleptic-treated patients made significantly smaller adaptive anticipatory saccades than either drug-free schizophrenic patients or normal subjects. These finding are discussed as they relate to the prefrontal cortex-basal ganglia circuits involved in the regulation of behavior by representational knowledge and the idea that the abnormal anticipatory saccades we observed represent a failure in the sensorimotor gating of information derived from internal representations. PMID- 1751622 TI - Fatty acid levels in the brains of schizophrenics and normal controls. AB - Essential fatty acids are important constituents of the brain. There is evidence that levels in blood of certain essential fatty acids and their eicosanoid derivatives may be abnormal. We now report that in the frontal cortex of schizophrenic patients there are significant differences from normal in the fatty acid composition of phosphatidylethanolamine. These differences from normal were not found in the cerebellar cortex. PMID- 1751623 TI - Neurological "hard" signs and family history of psychosis in schizophrenia. AB - Previous research found schizophrenics to have significantly more neurological signs than normal controls, even when signs were screened to exclude possible artifacts, and limited to "hard" signs of localizing significance. Schizophrenics with a family history of psychosis also tended to have more neurological signs than those without such a history. The present study examined whether these findings could be confirmed in new samples of schizophrenics and controls, using interview-based DSM-III and DSM-III-R diagnoses. Schizophrenics had significantly more hard signs than controls, and schizophrenics with a family history for psychosis again had more signs than those without this history. When present study data were analyzed alone, as well as when pooled with data from previous research using similar methods, hard signs were significantly greater in both (a) schizophrenics versus controls and (b) schizophrenics with versus without a family history of psychosis, supporting the hypothesis that neurological signs reflect a significant etiologic factor in schizophrenia. PMID- 1751624 TI - Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression. AB - Partial sleep deprivation (PSD), keeping a subject awake from 2 AM to 9 PM produces an acute mood improvement in 60% of patients with major depression. We sought to characterize the timing, subcomponent mood, and motor activity changes of this response. Thirty-seven subjects with major depression were rated with the 6-item Hamilton Depression Scale (HAM-6) at 1 PM and completed the Profile of Mood States (POMS) every 2 hr on the day before and day of PSD. Locomotor activity was monitored continuously during the trial with an automated device. Bipolar I patients responded more frequently than other groups. Positive mood responders had greater improvement than nonresponders in POMS subscales of depression, tension, confusion, and anger. The mood improvement increased steadily during the day, peaked in late afternoon, and declined thereafter. Responders showed significantly higher levels of locomotor activity on the baseline pre-PSD day than did nonresponders. All subjects increased motor activity following sleep deprivation, however. PMID- 1751625 TI - HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy. AB - To determine the association of HLA DR2 in patients with narcolepsy without cataplexy, a case-control study was performed. Patients receiving the diagnosis of narcolepsy without cataplexy had excessive daytime sleepiness (EDS) and polysomnographic findings consistent with narcolepsy but no clinical evidence of cataplexy. Of 28 patients identified, 12 agreed to return for HLA typing. Respondents did not differ from nonrespondents in demographic, clinical, or sleep laboratory data. The comparison group was 503 individuals, those 30 years and older, on the Michigan Kidney Transplant Registry. The odds ratio obtained from logistic regression indicated a strong association between narcolepsy without cataplexy and HLA DR2. To control for potential confounding variables, multivariate models were constructed to explore the joint effects of HLA DR2 and each one of the covariates (age, sex, and race), their possible combinations, and the effect of all three covariates. The odds ratios decreased minimally and the association between the disease and HLA DR2 remained significant. PMID- 1751626 TI - Increased platelet membrane lysophosphatidylcholine in schizophrenia. PMID- 1751627 TI - Prostaglandin E2 secretion by oviductal transport-stage equine embryos. AB - This study was conducted to identify embryonic products whose secretion was temporally associated with the oviductal transport period of the mare. Chemicals secreted by oviductal-transport-stage equine embryos were identified by incubating Day 6 or Day 7 early uterine embryos with 35S-methionine/cysteine, 3H progesterone, or 3H-arachidonic acid for 24 h, and subsequently identifying radioactively labeled proteins (SDS-PAGE; n = 3 embryos), steroids (HPLC; n = 3 embryos), or prostaglandins (HPLC; n = 3 embryos) in the culture medium. Early uterine embryos secreted 116.1 +/- 45.5 pg of prostaglandin (PG) E2/embryo, 1.0 +/- 0.2 pg of 17 alpha-hydroxy progesterone/embryo, 4.8 +/- 0.6 pg of androstenedione/embryo, and 11.5 +/- 4.5 pg of PGF2 alpha/embryo. They did not secrete detectable quantities of protein, testosterone, or estradiol-17 beta. A second experiment was conducted to measure temporal changes in embryonic PGE2 secretion during the oviductal and early uterine period. Day 3, Day 4, Day 5, and Day 6 embryos (n = 8 embryos/day) were incubated with 3H-arachidonic acid for 24 h, and the concentration of 3H-PGE2 in the culture medium was subsequently measured by HPLC. Embryos did not secrete detectable amounts of PGE2 prior to the expected time of oviductal transport (Day 3 and Day 4). They secreted 5.7 +/- 1.0 pg of PGE2/embryo immediately before and during the expected time of oviductal transport (Day 5), and they secreted significantly of PGE2/embryo immediately before and during the expected time of oviductal transport (Day 5), and they secreted significantly (p less than 0.01) higher amounts (42.0 +/- 11.5 pg) of PGE2/embryo immediately after uterine entry (Day 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751628 TI - Prostaglandin E2 hastens oviductal transport of equine embryos. AB - The hypothesis that treatment of pregnant mares with prostaglandin E2 (PGE2) hastens the oviductal transport of equine embryos was tested by treating bred mares with PGE2 on Day 3 after ovulation and subsequently measuring the rate of hastened oviductal transport (estimated by the uterine embryo recovery rate on Day 4 after ovulation). In a preliminary, noncontrolled experiment, oviductal transport was apparently not hastened after intramuscular, intrauterine, or intraperitoneal PGE2 administration to bred mares (0/6, 0/3, and 0/3 mares, respectively). Oviductal transport appeared to be hastened in 1/13 mares after a single intraoviductal administration of PGE2, and in 2/2 mares after continuous intraoviductal administration of PGE2. In a subsequent, controlled experiment, treatment with a continuous intraoviductal infusion of PGE2 hastened oviductal transport in significantly more (p less than 0.01) mares versus a continuous intraoviductal infusion of vehicle or no treatment (6/11 vs. 0/11 or 0/11 mares, respectively). Unfertilized oocytes and oviductal masses were also recovered from mare uteri after continuous intraoviductal PGE2 administration, but were not recovered after vehicle administration or no treatment. These results support the hypothesis that PGE2 treatment hastens the oviductal transport of equine embryos, and suggest a role for embryonic PGE2 in the initiation of selective oviductal transport in the mare. PMID- 1751629 TI - The effect of ovarian follicle size on pituitary and ovarian responses to copulation in domesticated South American camelids. AB - The relation of ovarian follicle size to pituitary and ovarian responses to copulation was studied in domesticated South American camelids (llamas and alpacas). Females from each species were divided into four groups according to follicle size: small (4-5 mm), growing (6-7 mm), mature (8-12 mm), and regressing (10-7 mm). The pituitary response to copulation was determined by analysis of LH and FSH concentrations in plasma. The ovarian response to copulation was determined by ultrasonography and by analysis of estrone sulfate (follicular status) and pregnanediol glucuronide (luteal status) concentrations in urine. Females with small follicles (4-5 mm) released less LH after copulation than did those with larger follicles, and ovulation was not induced. Females with growing and mature follicles (7-12 mm) released LH in response to copulation that was adequate to induce ovulation and to initiate normal luteal activity. While copulation-induced LH release in females with regressing follicles was similar to that released in animals with growing and mature follicles, regressing follicles were luteinized instead of being ovulated. The luteal structure formed as a result of luteinization of follicles had a short life span, i.e., 5.1 days. Copulation-induced LH release was significantly higher in llamas vs. alpacas in animals with mature or regressing follicles, but not in those with small or growing follicles. Urinary estrone sulfate and pregnanediol glucuronide concentrations correlated positively with the presence of follicles and corpora lutea, respectively. PMID- 1751630 TI - Cell-specific expression of guanine nucleotide-binding proteins in rat testicular cells. AB - Guanine nucleotide-binding proteins (G proteins) are key components in membrane signal transduction that may play an important role in testis function. The present study is the first description of cell-specific differences in the contents of G protein alpha-subunits and their mRNAs in isolated rat testicular cells (pachytene spermatocytes, round spermatids, Sertoli cells, peritubular cells). By using Western blot techniques G1-3 alpha was shown to be the only pertussis toxin (PTX) substrate present in all the testicular cells examined. Surprisingly, we observed a lack of immunoreactive Gi-1 alpha/Gi-2 alpha protein in pachytene spermatocytes and round spermatids in spite of significant levels of the corresponding mRNAs as revealed by Northern analysis. No immunoreactive Gs alpha was detected in germ cells, in agreement with previous findings that the hormone-sensitive adenylyl cyclase is absent in these cell types. Peritubular cells and Sertoli cells contained no Go alpha, whereas high levels of both immunoreactive protein and mRNA were found in pachytene spermatocytes. This indicates that the Go protein may play a role at this stage of spermatogenesis. The stimulation of phospholipase C (PLC) in germ cell membranes by 5'-guanylyl imidophosphate indicates that PTX-sensitive PLC activation may be mediated by Go alpha or Gi-3 alpha. PMID- 1751631 TI - The influence of extracellular matrix components on the proliferation and migration of inner cell mass-derived parietal endodermal cells. AB - Reichert's membrane is a basement membrane deposited on the inner surfaces of rat and mouse trophectodermal (TE) cells beginning at the blastocyst stage of embryonic development that may play a role in the migration of the parietal endodermal (PE) cells to form an inner lining to the TE. The abilities of various glycoproteins present in Reichert's membrane to support PE cell migration and replication in vitro were examined by isolating inner cell masses (ICMs) from Day 5 rat blastocysts (Day 1 = day of vaginal plug) and culturing them (24-72 h) either on surfaces that had been precoated with collagen IV, fibronectin, or laminin or on thin (1-2-mm) gels of Matrigel (a tumor cell-derived basement membrane preparation) or type I collagen. Time-dependent changes in the area occupied by each ICM on the culture surface and the number of migrating cells per ICM were quantified by morphometric analysis. Type IV collagen, the basement membrane-specific collagen, supported ICM attachment and the outward migration (overall increase of approx. 60-fold in mean ICM area occupied on the culture surface) and proliferation (cell doublings following every 24 h of culture) of laminin-containing PE-like cells. These effects were not altered by the inclusion of exogenous fibronectin or laminin in the culture medium. Collagen IV coating concentrations as low as 0.16 micrograms/ml supported PE cell attachment and migration, and maximal responses were seen with a coating concentration of 0.63 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751632 TI - Ovarian steroid production in vitro during gonadal regression in the turkey. I. Changes associated with incubation behavior. AB - The mechanism regulating ovarian regression during incubation behavior in the domestic turkey has not been elucidated. This study was designed to determine whether ovarian steroidogenic potential is depressed during gonadal regression associated with the onset of incubation behavior. Hens were housed in floor pens equipped with trap nests that were checked 7 times per day. Hens were grouped, according to nesting frequency and egg production, into the following classifications: laying (laid an egg every day and trapped in the nest only once/day); transitional (laid an egg every day but trapped in the nest 4 or more times/day); and Day 1, Day 3, and Day 5 incubating (no egg for 2, 4, or 6 days, respectively, while trapped in the nest at least 4 times/day). Follicular atresia was evident in the largest preovulatory follicle (F1) in transitional hens, extensive in F1 through the third largest follicle (F3) in Day 1 incubating hens, and extensive in F1 through F7in Day 3 incubating hens. Levels of circulating LH, progesterone (P), androgen (A), and estradiol (E) decreased in transitional hens relative to concentrations in laying hens and remained low thereafter. In contrast, levels of prolactin were greater in Day 3 and Day 5 incubating hens than in laying, transitional, or Day 1 incubating hens. Basal production of P by F1 granulosa cells was lower from Day 1 incubating hens than from the other groups. Production of P in response to porcine-luteinizing hormone (pLH) was greater by cells from transitional and Day 1 incubating hens than from those of laying hens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751633 TI - Ovarian steroid production in vitro during gonadal regression in the turkey. II. Changes induced by forced molting. AB - In the turkey, the onset of incubation behavior is associated with altered ovarian steroidogenesis, ovarian regression, decreased, LH secretion, and increased serum prolactin (Prl) levels. To clarify the relative contribution of circulating LH and Prl to the initiation of ovarian regression, laying hens were exposed for 0, 3, 7, or 14 days to a forced molting procedure (exposure to reduced day length of 6L:18D and removal of feed and water for the initial 3 days) that induces ovarian regression and decreased LH levels but does not increase Prl levels. On each of these days, hens were killed and granulosa and theca interna cells from the largest (F1) and fifth largest (F5) preovulatory follicles and total cells from the small white follicles (SWF) were incubated for 5 h in the presence or absence of ovine LH (oLH; 0-1,000 ng/ml). Force-molted hens exhibited diminished levels of circulating LH, Prl, progesterone (P), androgen (A), and estradiol (E) by Day 3 of treatment. Ovarian atresia began in F1 by the third day of treatment, and included F1 and F5 by the seventh day. No preovulatory follicles were present on the fourteenth day. With both F1 and F5 granulosa cells, production of P in the presence of oLH was initially enhanced (Day 3) and later absent (Day 7). In contrast, production of A by F5 theca interna cells in the presence of oLH was initially suppressed (Day 3) and then returned to pretreatment levels (Day 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751634 TI - Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo. AB - The sialylation of eCG was examined to determine its influence on the in vivo metabolism and biological activity of the molecule. Sialic acid was decrementally removed from eCG by incubation with agarose-linked neuraminidase for varying time periods. Pharmacokinetic parameters for the disappearance of 4,000 IU (267 micrograms) of three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and control eCG were determined in sheep. The clearance rate of eCG increased (p less than 0.05) with each decrement of sialic acid. The removal of 53% sialic acid enhanced the distribution of eCG into the tissues, compared to control and 20% desialylated eCG (p less than 0.05), presumably because of increased lipid solubility and decreased molecular size. Desialylation to 53% did not alter the elimination half-life of eCG. The removal of 80% sialic acid resulted in the disappearance of eCG from the serum within 1 h, whereas control eCG was still present at 120 h. In vivo trials in rats disclosed that the control eCG preparation increased ovulatory rate at doses of 10-100 IU and ovarian weight at doses of 10-300 IU relative to saline-treated rats (p less than 0.01). The 20% desialylated eCG induced superovulatory and ovarian weight responses, but 100-500 IU were required to achieve the same result as that produced by control eCG. The 53% and 80% desialylated eCG preparations induced a mild superovulatory response (p less than 0.01) but no ovarian weight response. It was concluded that sialic acid was significant to the distribution and disappearance of eCG. The effects of carbohydrate removal on biological activity (e.g., superovulation) are primarily a function of clearance rate rather than tissue-specific phenomena. PMID- 1751635 TI - Further characterization of the electromyographic activity of the myometrium and mesometrium in nonpregnant sheep under estrogen supplementation. AB - The effects of estrogen administration on uterine contractility varies with animal species. In nonpregnant ovariectomized sheep, estrogen administration has been reported either to inhibit, inhibit then stimulate, or only stimulate uterine contractility. The aim of the present study was to determine the effects of prolonged estrogen administration in the electromyographic (EMG) activity recorded from the myometrium and mesometrium in nonpregnant ovariectomized sheep after estrous synchronization by inserting vaginal progesterone sponges 14 days before surgery. Surgery was performed on four ewes under halothane anesthesia. Bilateral oophorectomy was performed, and stainless steel EMG electrodes were sewn to the mesometrium and myometrium in both left and right horns of the uterus. Blood samples were taken at 1000 h from the uterine vein for 13,14 dihydro-15-keto-prostaglandin F2 alpha determination, and from the femoral artery for estradiol determination. Starting on Day 7 after surgery, estradiol 17 beta (50 micrograms/24 h) was infused continuously into the jugular vein. Estrogen administration had a different effect on the EMG activity recorded from myometrium and mesometrium. The myometrial response to estrogen was an increase in the frequency of short EMG events from 19.0 +/- 8.7 to 57.0 +/- 5.0 (p less than 0.05) for events less than 60 sec, and from 2.70 +/- 0.83 to 10.30 +/- 1.36 (p less than 0.05) for events lasting greater than 60 sec but less than less than 180 sec. In contrast, there was no stimulatory effect of estrogen on mesometrial EMG for both types of short events less than 60 sec, and greater than 60 but less than less than 180 sec.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751636 TI - Activation of reproduction in nulliparous and primiparous voles is blocked by vomeronasal organ removal. AB - Chemical cues from male voles activate reproduction in female prairie voles (Microtus ochrogaster). Twelve hours of contact with a male, followed by exposure to his soiled bedding for 2 days, is sufficient to initiate follicular maturation and induce uterine hypertrophy. Our recent work indicates that the chemosensory vomeronasal organ (VNO) can mediate this response. Here, we examined whether other sensory systems can acquire the ability to activate female reproduction as a result of learning or experience. To explore this issue, the VNO was removed (VNX) from nulliparous and primiparous females who were then exposed to cues from males. In Experiment 1, we found that nulliparous VNX females had lower uterine and ovarian weights than did sham-operated females. In Experiment 2, we determined that sexual experience did not ameliorate the reproductive deficits normally induced by VNX. The present results contrast with those of previous studies suggesting that males of some rodent species, when allowed reproductive experience prior to VNX, can utilize other sensory systems to mediate subsequent reproductive responses. We conclude that the role of the VNO in transducing chemosensory information is crucial for coordinating the reproductive efforts of male and female prairie voles. PMID- 1751637 TI - Temporal structuring of delivery in the absence of a photoperiod: preparturient myometrial activity of the rhesus monkey is related to maternal body temperature and depends on the maternal circadian system. AB - No convincing evidence exists that the shift from myometrial contractures to contractions, which determines the synchronized 24-h rhythm in the dynamics of the primate uterus, may be attributed to an endogenous circadian rhythm. We therefore wished to ascertain whether a 24-h periodic shift would also occur in the myometrial activity of animals kept under constant conditions. We studied five pregnant rhesus monkeys, kept in continuous darkness from 56-77 days gestational age until delivery at 117-167 days gestational age. During the last week before delivery we determined the individual phase, level, and amplitude of circadian changes in maternal body temperature and 24-h myometrial activity patterns in the form of contractions. In all five monkeys, a rhythm with a period of 24-h characterized the temporal incidence of preparturient contraction activity. A consistent phase lag of 6-7 h from the temperature crest was observed in four out of the five animals. The circadian phase of all individual rhythms was idiosyncratic among animals. We conclude that endogenous rhythms in body temperature and preparturient myometrial activity are truly circadian. In addition, these rhythms are either interdependent or subject to the same maternal timekeeping mechanism, supporting the hypothesis that the exact time of the day at which birth occurs in the rhesus monkey depends on the maternal circadian system. PMID- 1751638 TI - The critical period for mullerian duct regression in the dog embryo. AB - The embryonic period during which Mullerian duct regression and Mullerian Inhibiting Substance (MIS) secretion occur was determined in canine embryos removed from timed pregnancies (32, 36, 37, 39, 42, and 46 days gestation). Sex chromosomes of each embryo were identified in metaphase spreads prepared from fibroblast cultures. Testicular differentiation, defined by seminiferous tubule formation and the presence of Sertoli cells and Leydig cells, and the degree of Mullerian duct regression were determined by careful morphologic analysis of histologic sections of canine embryonic gonads (n = 20) and Mullerian ducts (n = 20). MIS was detected immunohistochemically in embryonic testes using avidin biotin complex enhancement of a specific rabbit polyclonal anti-MIS antibody. Testicular differentiation was observed at 36 days gestation. The earliest evidence of Mullerian duct regression in male embryos was observed at 36 days gestation, and regression was completed by 46 days gestation. Positive staining for MIS was present in testes from 36 to 46 days (n = 9). Staining was absent in the undifferentiated testis (n = 1) at 32 days gestation and in ovaries at all ages tested (n = 10). Thus, MIS is normally present throughout the critical period for Mullerian duct regression in the embryonic male dog. PMID- 1751639 TI - Regulation of androgen receptor mRNA in rat Sertoli and peritubular cells. AB - Regulation of 9.5-kb androgen receptor mRNA concentrations in Sertoli and peritubular cells from 20-day-old rats was studied by Northern blot analysis. Treatment of cells in vitro for 1-7 days with 300 ng/ml FSH increased androgen receptor mRNA up to 4-fold in Sertoli cells but not in peritubular cells. Testosterone (100 ng/ml) had no effect or slightly decreased androgen receptor mRNA in Sertoli and peritubular cells. Androgen receptor mRNA concentrations in Sertoli and peritubular cells from rats killed 15 days after hypophysectomy were elevated 4-5-fold over those in cells from intact rats. The androgen receptor mRNA concentration was decreased in both Sertoli and peritubular cells isolated from hypophysectomized animals treated with 500 micrograms/day testosterone propionate in vivo and subsequently with 100 ng/ml testosterone in vitro. FSH treatment (100 micrograms/day in vivo, followed by 300 ng/ml in vitro) did not increase androgen receptor mRNA over that in cells from hypophysectomized controls but rather decreased its concentration to varying degrees in Sertoli and peritubular cells. The rise in androgen receptor mRNA in both Sertoli and peritubular cells isolated from hypophysectomized animals is attributable, at least in part, to the absence of the inhibitory influence of testosterone. Other data in the literature suggest positive regulation of Sertoli cell androgen receptor protein by FSH and androgens. Consequently, complex mechanisms involving transcriptional, translational, and post-translational regulation probably control androgen receptor concentrations in the cells of the rat seminiferous tubule. PMID- 1751640 TI - Cardiomyopathies in children with neuromuscular disorders. AB - In this paper eight patients with myogenic or neurogenic muscle disorders are presented, in whom cardiomiopathy was also found. Six patients developed a dilated cardiomiopathy associated with neurogenic atrophies or progressive muscular dystrophy. In patients with Mb. Friedreich and HSNM type II together with the total dilatation of the septum hypertrophy was observed and in patients with spinal muscular amyotrophy of scapuloperoneal type atriomyopathy dominated. In two patients with mitochondrial disorders a hypertrophic cardiomyopathy was found. One of them had mitochondrial encephalomyoneuropathy and the other mitochondrial encephalopathy with myoclonic epilepsy. In none of them a restrictive cardiomyopathy was found. From the presentation could be concluded that in neurogenic muscle diseases and progressive muscular dystrophy respectively most frequently dilated cardiomyopathies have been developed. Hypertrophic cardiomyopathies are usually found in children with mitochondrial disorders. PMID- 1751641 TI - Diagnostic possibilities of closed head injuries of acceleration type using computed tomography. AB - A group of 42 patients with closed head injuries of acceleration type is reported. All of them were treated at various departments of the General Hospital in Maribor. The aim of investigation was to find out the diagnostic possibilities of head and brain damages in closed head injuries of acceleration type by the method of computed tomography (CT) and making comparison with the clinical picture of each individual patient. The patients were not investigated at random but were grouped in accordance with the direction of traumatic force action. The CT analyses were performed according to characteristic patterns of traumatic brain disease. The circumstances of head injury were reliable guidelines for devoting more attention to some brain areas. The density of each lesion was examined, too. The investigation has shown that lesions of "inner cerebral trauma" pattern (ICT-Grcevic 1965) are visible on CT at least as often as coup contrecoup lesions or even more. Only in cases with latero-lateral direction of traumatizing force (control group) coup-contrecoup lesions were found more frequently. Deep cerebral lesions of the latero-lateral type of acceleration head trauma were never or seldom encountered. PMID- 1751642 TI - Cerebrospinal fluid CK enzyme and CK isoenzymes in the outcome prognosis of cerebrovascular disease. AB - The article presents the results of the analysis of total CK enzyme activity and CK isoenzymes in the cerebrospinal fluid of 148 patients with acute stroke, treated at the Intensive Care Unit of the Department of Neurology and Department of Neuropathology of the Clinical Hospital Center Rebro. The aim of the study was to determine the reliability of the applied methods in the prognosis of the outcome of cerebrovascular diseases. Greatly increased total CK enzyme activity is more frequently encountered in patients with ICH than in those with ISI. Great elevation of total CK activity can be considered a bad prognostic sign in patients with ICH, while in those with ISI only moderately increased total CK enzyme activity can be regarded as a bad prognostic sign. The greatest incidence of pathological CK isoenzyme profile, that is the presence of both MM and BB fractions together, was found in the group of patients who died with ICH, while the greatest frequency of BB fraction alone was observed in the group of patients who survived with ISI. In the group of the deceased with ISI the greatest frequency was that of MM and BB fractions together. Therefore, the occurrence of BB fraction alone can be considered a good prognostic sign, while the occurrence of MM and BB fractions together a bad one. The presence of MM and BB fraction together, as well as the simultaneous presence of all three fractions of isoenzymes, are most frequently associated with elevated total CK enzyme activity. The occurrence of BB isoenzyme fraction alone is most frequently accompanied by normal value of total CK activity, rarely with slightly to moderately, and very rarely with greatly increased total CK enzyme activity. The determination of total CK activity and of CK isoenzyme profile is performed by means of two complementary investigations which should be performed simultaneously. PMID- 1751643 TI - Transcranial Doppler diagnostic criteria in the evaluations of arteriovenous malformations. AB - In order to get a better insight in hemodynamic occurrence of intracranial arteriovenous malformations (AVM), 31 patients with AVM, documented by CT and angiography, were investigated by Transcranial Doppler (TDC). Although the angiography provides definite diagnosis of AVM, its size, position, type feeders and involvement of various vascular segments, TCD provides more information about collateral circulation, intracerebral shunts or functional stenosis due to high blood velocities within the blood vessels involved by AVM. The parameters obtained by TCD: mean cerebral blood flow velocities (MCBFV) in middle and internal carotid artery (MCA, ICA), pulsatility index (PI), MCA/ICA ratio and (S D)/S ratio were introduced. Results have shown that TCD findings in non-feeding arteries were normal in all patients. TCD finding of MCBFV in MCA and ICA, PI and MCA/ICA ratio in feeding arteries has shown a significant difference from normal arteries (p less than 0.01). These parameters are shown to be AVM size dependent. MCBFV in MCA on the feeder side was statistically significant higher in those patients with large AVM (greater than 4 cm) size (p less than 0.01). For assessment of AVM and its improved and advanced analysis the potential advantages of parameters: (S-D)/S ratio and 3D hemodynamic mapping has been emphasised. PMID- 1751644 TI - Regional distribution of brain gangliosides in Alzheimer's disease. AB - In this study, brain gangliosides of patients with Alzheimer's disease (AD, N = 5) were analyzed and compared with control human brains (C, N = 3). Gangliosides were analyzed in seven brain regions: cerebral cortex (frontal, parietal, temporal and occipital), hippocampus, basal telencephalon and frontal white matter. The results demonstrated gangliosides to be decreased in the majority of regions analyzed, however, a significant decrease in gangliosides (nmol LBSA/mg proteins or g fresh weight) in frontal cortex and white matter (P less than 0.05) was recorded. When gangliosides were expressed in nmol LBSA/mg DNA (deoxyribonucleic acid), their basal telencephalon, suggesting that high astroglial proliferation might have concealed the real neuronal degeneration. In the ganglioside composition, all human brain regions contained moderately decreased ganglio-series gangliosides (GT1b, GD1b, GD1a, GM1) but a statistically significant decrease was detected in frontal cortex, and white matter (nmol LBSA/g fresh weight) or frontal cortex, temporal cortex and basal telencephalon (nmol LBSA/mg DNA). In addition, frontal and parietal cortex also showed elevated concentration (nmol LBSA/g fresh weight) of simple gangliosides (GM2, GM3, GM4, GD3). A decreased concentration of ganglio-series gangliosides in Alzheimer's disease correlates with degeneration of cortical neurons. However, elevation of simple gangliosides in frontal and parietal cortex may correlate with: (a) an accelerated lysosomal degradation of gangliosides occurring during neuronal death (GM2); (b) astrogliosis (GM3 and GD3); and (c) activation of oligodendrocytes (GM4). The fact that gangliosides are altered in Alzheimer's disease might be important for better understanding of the pathogenesis of the disease. PMID- 1751645 TI - Development of carotid stenosis. AB - A group of 29 patients with carotid artery stenosis was analyzed with the purpose of following-up the development of stenosis, and performing duplex scanner of carotid arteries. The follow-up was performed on the very first day of the study and six months later. There were 49 stenoses of internal carotid arteries in 29 patients. Carotid stenoses were classified into six categories. Most carotid stenoses were unchanged during the six month period (57.2%), or progressed (36.7%), but spontaneous regression was found in 6.1%. The ultrasonic characterization of carotid plaques was made in four types. Regression was noticed mainly in ulcerative plaques, while hard and fibrous plaques remained unchanged or progressed. Soft plaques progressed in all cases. Intraplaque hemorrhage was found in 2 patients. The most common risk factors for carotid atherosclerosis were hypertension, hyperlipidemia and cigarette smoking. PMID- 1751646 TI - Sleep-waking cycle disturbance in patients with obstructive sleep apnea syndrome. AB - Eighteen (18) obese patients with clinically confirmed obstructive sleep apnea syndrome (OSAS) and five (5) obese persons with no apnea crises noticed during sleep apart from occassional loud snoring, have been polysomnographically assessed. The obtained results show that the patients with apnea syndrome sleep very badly, and consequently, shortened sleep latency and frequent body movements, along with apneas, are regarded as the leading polysomnographic symptoms. Vigilance profile during sleep, that is, interchange and frequency of each of sleep stages (I, II, III, IV, REM) are similar in both tested groups. The suppression of restitutive stages of sleep (III, IV, REM) is considered to be a dominant characteristic of vigilance during sleep in obese persons and obese persons with manifest apnea syndrome. Relatively prolonged sleep latency in obese persons without manifest apnea syndrome indicates, however, restitutively higher quality of their nocturnal sleep. Contrary to the patients with apnea syndrome, they do not suffer from excessive evening somnolence, so that their daily alertness and sleep vigilance during night are of a better quality, although the lack of deep and REM sleep is observed in them as well. PMID- 1751647 TI - The clinical picture of rabies in a child. AB - An eight-year-old boy developed rabies 31 days after having been scratched by a dog and died 9 day later. Intensive supportive medical treatment was complicated by apnea, cardiac arrest, hypotension, increased secretion of antidiuretic hormone and severe hypoproteinemia. The treatment with intramuscular human antirabies immunoglobulin (HRIG) 2400 I.U. and intrathecal 1200 I.U. in combination with intramuscular interferon alpha 4 million I.U. was given every second day. The diagnosis of rabies was confirmed before death, on the third day of the disease, by direct fluorescent antibody staining of the saliva and cerebrospinal fluid for viral antigen. At the autopsy, the brain tissue specimens were tested for the presence of the virus by inoculation into the suckling mice brain and for the viral antigen by direct fluorescent antibody method. The brain tissue specimens collected at autopsy were also tested for virus by direct fluorescent antibody method. PMID- 1751648 TI - Dumbbell meningioma of the cervico-clavicular region. AB - The authors are reporting on a case of a 55-year-old man with an epidural meningioma in the region from the C VII. to the Th I. segment. The tumor encircled this region, and to the front and right involved the channels through which pass the C VI, C VII. and C VIII. roots. Subdurally, no tumoral mass was found. Another part of this tumor, of the same histological architecture as the epidural cervicospinal part was found in the supraclavicular region to the right, closely connected to the arteries and nerves of this region. The authors discuss the possibility of the tumoral occurrence at this site, primarily taking into account the origin of this tumor from the cells of the outer surface of the arachnoidea, i.e. cap cells which can invade the dura, with later separation from the main arachnoidal layer. The other possibility of such dumbbell meningioma occurring at the outgoing openings of the neural paths from the spinal channel should be looked for in the remnants of the arachnoidal cells in the region of the outgoing openings. In the paper are also discussed and correlated clinico pathological, CT and angiographic findings. PMID- 1751649 TI - [Stress and anesthesia]. PMID- 1751650 TI - [The endocrine stress reaction in anesthesia and surgery--origin and significance]. AB - Stress can be defined as a "reaction by living beings to any relevant impairment". The effect of anaesthesia on endocrine function is closely related to the actual stress concept based on the works by Cannon and Selye. Cannon described the role of catecholamines in stress and characterised the fight-flight reaction. Selye emphasised the role of the adrenocortical reaction defining the "general adaptation syndrome", which evolves in three stages ("alarm reaction", "stage of resistance", "stage of exhaustion"). Later, Henry postulated the dual stress concept. The sympathetic-adrenomedullary system is activated during the fight-flight reaction, thus representing an active role of the organism. The pituitary-adrenocortical system is activated during loss of control, submission and depression, especially in a social context. Main valid parameters of this endocrine stress response are adrenaline, noradrenaline, ADH, ACTH and cortisol. In the perioperative period, both pathways are "stressed". The most important factors are patient, operation, and anaesthesia. Anaesthesia can influence the stress response by afferent blockade (local anaesthesia), central modulation (general anaesthesia) or peripheral interactions with the endocrine system (etomidate). Up to now, a total peripheral blockade of the nociceptive system is impossible, due to surgical technique (destruction of nerve fibres) and release of mediator substances. With regard to reduction of endocrine stress response, inhalation anaesthesia with volatile anaesthetics and nitrous oxide may be less effective than neuroleptic, spinal or epidural anaesthesia. Immediately after extubation, rapid increases of endocrine parameters are observed. In addition to central modulation of pain and stress, both halothane and enflurane inhibit catecholamine release from the adrenal medulla. Neuroleptic anaesthesia and total intravenous anaesthesia are very potent and sufficient to control the increases in endocrine parameters even during major surgery, due to their central effects. Spinal and epidural anaesthesia alone as well as in combination with general anaesthesia can reduce the endocrine stress response more than necessary. This is due to the sympathetic blockade, combined with an afferent blockade of central cord fibers which modulate the pituitary-adrenocortical system. Only few data are available concerning the stress response during infiltration anaesthesia or nerve block, but additional sedation seems to be beneficial. Peripheral interactions with the endocrine system like blockade of the adrenal cortex by etomidate is dangerous and has caused a high mortality in intensive-care patients if the substance was admitted for a longer period. Assessment of endocrine stress response in anaesthesia and surgery is controversial.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1751651 TI - [Optimized analgesic sedation techniques for ESWL]. AB - Analgo-sedation for ESWL treatment has been associated with a variety of problems. Minimal invasiveness of this technique should combine with haemodynamic stability as well as with adequate oxygenation. Patient acceptance has to be considered as another important aspect. Our study demonstrates the effectiveness of an analgosedative regimen with regard to these aspects. 50 ASA I-III patients scheduled for ESWL treatment were randomly allocated to receive either no premedication (n = 25) or chlorazepam as oral premedication (n = 25). The analgosedative technique was identical in both groups, consisting of atropine 0.25 mg, droperidol 5 mg (2.5 mg, if body weight less than 60 kg), and alfentanil 10 micrograms/kg intravenously. If necessary, repeated boluses of alfentanil 5 micrograms/kg were administered up to a maximum of 2 mg. Heart rates, arterial blood pressures, and peripheral oxygen saturation were measured during treatment. Post-treatment, patients were interviewed to assess the quality of analgesia. The results showed that our analgo-sedative regimen is suitable for ASA I-III patients. Stable heamodynamic conditions and adequate oxygenation were achieved in all patients. Patient acceptance was good. Patients with anxiolytic premedication benefited in terms of reduction in blood pressure and heart rate. The study also showed that anaesthesiologists may underestimate the pain intensity experienced and assessed by the patient. PMID- 1751652 TI - [Muscle relaxation using atracurium in porphyria variegata--case notes]. AB - A case is presented involving the use of atracurium (120 mg) as a muscle relaxant in a patient with known variegate porphyria. The concentrations of urinary porphyrins and porphyrin precursors did not increase after this anaesthetic, and no exacerbation of the disease was noted. This single case suggests that atracurium can be used safely in patients with porphyria. PMID- 1751653 TI - [In vitro drug interactions and their importance in anesthesiologic practice]. AB - The potential for in vitro drug interactions is great in anaesthesiology because of routine intravenous comedication. When the drug is applied directly into (via) the injection port of the cannula most of these interactions are overlooked, whereas others show no visible signs. Chemical interactions depend on pH changes, formation of insoluble salts, oxidation and reduction, complex formation, or hydrolysis. Physical interactions are caused by changing of solvent system polarity, salting out, emulsion cracking or sorption. Solving the problem requires information (1) and precautions in respect of the mode of application (2). (1) Anaesthesiologists should know the most frequent mechanisms. Glucose infusions cannot be considered as safe carrier solutions for admixtures. Pharmacological databases should offer as much information as possible on incompatibility. (2) Injections into a separate line or lumen with a sodium chloride infusion are safe. Admixture is recommended only if compatibility is known. PMID- 1751654 TI - [Mini-Symposium. Intensive medicine 1991. Introduction]. PMID- 1751655 TI - [New aspects of enteral nutrition]. PMID- 1751656 TI - [The effect of nutrition on the work of breathing]. PMID- 1751657 TI - [Nutrition in acute kidney failure]. PMID- 1751658 TI - [Endocrine dysfunction in critically ill patients]. PMID- 1751659 TI - [New ventilatory techniques]. PMID- 1751660 TI - [Intensive medicine aspects of pre-eclampsia--eclampsia]. PMID- 1751661 TI - [Compartment syndrome of the forearm due to infusion and transfusion using a pressure pump]. AB - Two cases are reported in whom infusions and transfusions by means of pressure pumps caused a compartment syndrome of the forearm. Subfascial tissue pressure measurement is a decisive device under general anaesthesia to confirm the diagnosis. The development of a compartment syndrome caused by extracorporal fluids, be it an arthroscopy or a transfusion, as well as the indication for a conservative or an invasive procedure are discussed. PMID- 1751662 TI - Overview: techniques and indications of LDL-apheresis. AB - In recent years, LDL-apheresis has emerged to be an efficient treatment of hyperlipidemia in patients who do not respond sufficiently to diet and lipid lowering drugs. A survey of LDL lowering extracorporeal procedures is presented. Among them, to date 5 procedures have been used clinically on a routine basis: unselective plasma exchange, semi-selective double filtration (including its modifications like thermofiltration and predilution/backflush) and three highly selective LDL-apheresis systems: LDL-adsorption on dextran sulfate coated cellulose beads or anti-apoprotein B-linked sepharose and heparin induced extracorporeal LDL and fibrinogen precipitation (the so-called HELP system). Advantages, limitations and special indications of these commercially available systems are discussed. If atherosclerosis can really be made regress by drastic reduction of elevated serum cholesterol levels as indicated by recent publications, lipid apheresis will no doubt play a major role in attaining this goal. PMID- 1751663 TI - Basic studies of local adsorption in burn treatment. AB - The model of a full-thickness thermal burn in rats was used to demonstrate that the application of adsorptive dressings made of a fibrous activated carbon material (ACFM) after early excision of a burn crust exerts a considerable influence on the development of both local and general symptoms of burn disease. Three days after the excision a water content in underlying tissues falls from 84.81 +/- 0.62% to 54.47 +/- 4.2%, the wound surface area decreases by 10%, while this surface area under gauze bandages increases by 6.3%. The local adsorption results in lower activity of proteolytic serum enzymes and toxicity of blood serum in burned animals as well as in the positive dynamics of changes in functional activity of the immune system. By the 14th day the T-cell activity in animals with adsorptive carbon dressings was by 3.2 times higher than that in the animals with gauze bandages. The level of B-cell response if ACFM is applied exceeds normal values to a great extent, starting from the first days after the excision of a burn crust. PMID- 1751664 TI - Application sorption: experience in clinical use and prospects of development. AB - The analysis of experimental - clinical results obtained during the last decade in the field of application of adsorptive carbon dressings in wound and burn therapy is given. Possible mechanisms of the therapeutic effect of this material are discussed, the feasibility of their application during different phases of wound process and burn disease treatment is demonstrated. The local absorption may be independent efficient method of treatment in the case of surface burns and wound with a small area of injury and provide a pronounced detoxifying effect in the case of suppurative-septic complication of a mechanical trauma and burns. PMID- 1751665 TI - A study of oral adsorbent in chronic renal failure. AB - In order to examine the effect on the progression of chronic renal failure (CRF), we have applied an oral adsorbent (AST-120) composed of spherical porous carbon particles to patients with chronic renal failure undergoing conservative therapy. Its effect was observed in improvement of uremic symptoms, improvement of slope in linear regression of reciprocal of serum creatinine vs. time plots and delayed initiation of hemodialysis, compared to control patients, together with reduced uremic peak 2a in HPLC analysis of serum and lower levels of beta 2 microglobulin in AST-120 group than in control. The improvements of uremic symptoms, creatinine and 2a levels were confirmed in double blind study where background of patients were evenly randomized between AST-120 and placebo groups and no improvement was observed in placebo group. The result leads us to conclude that the oral adsorbent therapy is expected as an useful therapy for retardation of progression of CRF. PMID- 1751666 TI - Enterosorption in oncotherapy. AB - Patients with lymphogranulomatosis undergoing radiotherapy according to the radical scheme were treated with fibrous carbon enterosorbent VESTA in tablets for 14 days (group I, 23 patients) from the moment of leukopenia development (lower then 2.2 x 10(9)/l) or were traditionally treated using parenteral administration of hemostimulants, hemosubstitutes and detoxicants (group II, 23 patients). After 14 days leukopenia was cured in 18 patients of group I (78%) and in 11 patients of group II (48%), with an average number of leukocytes in the patients of groups I and II growing by 2 and 1.6 times, respectively. The administration of enterosorbents enabled interruptions in radiotherapy caused by the development of leukopenia and the deterioration of health status to be greatly shortened and the requirements in expensive transfusion media to be sharply reduced. PMID- 1751667 TI - Treatment of neuroleptic malignant syndrome with direct hemoperfusion. AB - Neuroleptic malignant syndrome (NMS) is an uncommon but serious and fatal idiosyncratic reaction to neuroleptics. It is difficult to correct this abnormalities successfully. There has been several reports on the treatment of NMS with dantrolene and/or bromocriptine. But these therapy are not effective in every cases. We have experienced ten cases of NMS. Six of them were presented with respiratory distress. Seven patients were treated with direct hemoperfusion and the remainder were managed by dantrolene, bromocriptine and other drugs. Patients treated with direct hemoperfusion two to four times could got a good improvement within several days and recovered. As to the patients treated by drugs. One of them who was not serious recovered with bromocriptine after twenty days. Two patients needed hemodialysis. NMS is occur not only by the use of neuroleptics but also by the break of them. So, this syndrome is do not develop by the high concentration of neuroleptics merely. NMS differed from ordinary drug intoxication. The etiology of NMS has unknown. But two major theories are present. One is dopaminergic blockade theory the other is direct toxic effect on skeltal muscles. We speculate that direct hemoperfusion remove metabolites of neuroleptics or normalize the alteration in the central nervous system. PMID- 1751668 TI - Anticoagulant therapy in a congenital antithrombin III (ATIII)-deficient patient with chronic renal failure undergoing regular hemodialysis. AB - We describe a 43-year-old male patient with congenital antithrombin III deficiency requiring hemodialysis due to extension of venous thrombus from recurrent deep vein thrombosis. During dialysis with adequate heparinization, the patient often revealed clot formation in the extracorporeal circuit resulting in unexpected discontinuation of dialysis. When either a combination of antithrombin III concentrate + heparin or the newly developed synthetic antithrombin preparation, MD805, was administered during dialysis, he could be uneventfully dialyzed with either of the two regimens. PMID- 1751669 TI - Long term effect of LDL apheresis in Japan. LDL Apheresis Study Group. AB - LDL-apheresis is introduced in many cases all over Japan. Among them, evaluation of long-term effect on ischemic heart disease (IHD) has made on 10 cases with homozygous familial hypercholesterolemia (FH) and 49 cases with heterozygous FH. As to homozygous FH, 3 patients had angina pectoris. Mean duration of treatment was 26 months (52 treatments). The changes in total cholesterol (TC) in each treatment was from 426 mg/dl to 151 mg/dl. Improvement in IHD was observed in 5 out of 10 cases. As to heterozygous FH, 17 cases had history of myocardial infarction and 12 had angina pectoris. Mean duration of treatment was 13 months (19 treatments). Mean TC was decreased from 271 mg/dl to 126 mg/dl by each treatment. Regression in Achilles tendon thickenting or skin and palpebral xanthomas was observed. Frequency of anginal attacks decreased in 8 out of 17 cases. Ischemic change in ECG were improved in 3 out of 26 cases. Coronary angiography performed with 2 to 3 years of interval in some cases revealed regression or no progression in coronary stenosis. As a whole, IHD improved in 15 cases and exacerbated in 2 cases. Main side effect was hypotension attack. Bradycardia and anginal attack during treatment were observed in some cases. LDL apheresis was judged as effective in 25 out of 44 patients with IHD or xanthoma. PMID- 1751670 TI - Application of plasma perfusion in hepatic failure. AB - To evaluate the efficacy of plasma perfusion as a liver-assistance system, 17 patients with hepatic failure were treated with a total 37 sessions of plasma perfusion and 43 sessions of plasma exchange. For plasma perfusion, Plasma-flo AP 08-H was used as a plasma separator, and the separated plasma was passed through an adsorber, Bespore UPC-III (Jap.Med.Suppl., Hiroshima) or BR 350 (Asahi Med. Co., Tokyo). The mean treated plasma volume was 5.0 liters. The mean proportion of bilirubin removed by routine plasma exchange was 29% with a mean of plasma exchange volume of 2.1 L. In the plasma perfusion with Bespore and BR, the removal rates were 37% and 42%, respectively. The plasma ammonia level decreased by 16% (from 121 to 97 mumol/L) with plasma exchange. Likewise, plasma perfusion decreased the plasma ammonia level from 75 to 56 mumol/L with an average decrement rate of 23%. The capacity for removal of amino acids was analyzed in terms of the change in the Fisher score ([Val+Leu+Ileu]/[Tyr+Phe]). The Fisher score was improved by plasma perfusion from 1.8 to 2.4. Thus, we concluded that in terms of removal of bilirubin, ammonia and amino acids, plasma perfusion was as efficient a therapy as plasma exchange. However, further clinical evaluation will be required before this procedure can be applied for the treatment of hepatic failure. PMID- 1751671 TI - Efficacy and limitations of plasma exchange in patients with acute hepatic failure; comparing with hemoadsorption, and with impaired regeneration syndrome. PMID- 1751672 TI - Assortment of posthepatectomy hyperbilirubinemia by the occurring time with reference to indication of plasma exchange. AB - This study was undertaken to assort the group of posthepatectomy hyperbilirubinemia by occurring time for helping elucidate its indication of plasma exchange (PE). PE was carried out for 14 cases among 198 hepatectomized patients. The 14 cases were classified for 3 groups due to the period between operation and PE. 1: Early type (less than 2 weeks), 2:Intermediate type (2 less than-less than 8 weeks), 3: Late type (greater than 8 weeks). The results were as follows. Number (liver cirrhosis (LC)) [table: see text]. The effect was expected for the early groups since PE would remove overload against the regenerating residual liver. However, there were no survival cases among the early group or LC group. These results suggest that PE may be effective for the slowly increasing hyperbilirubinemia in not cirrhotic patients and that the state of hyperbilirubinemia is the terminal stage for LC patients even under the particular situation such as posthepatectomy. PMID- 1751673 TI - Self-regulated delivery of insulin from microcapsules. AB - We previously developed self-regulating insulin delivery systems using concanavalin A (Con A)-bound succinyl-amidophenyl-glucopyranoside insulin (SAPG insulin) in pouch membrane which exhibited long lag times for exchange diffusion in response to glucose changes. We report here the preparation of a new system with a short exchange diffusion onset composed of hydrophilic nylon microcapsules containing Con A and SAPG-insulin in vitro. It is considered that this SAPG insulin system can quickly respond to glucose changes when it is composed of at least two layers which include active Con A and where unbound SAPG-insulin permeation is the rate limiting step. PMID- 1751674 TI - Polystyrene latex particles: preparation and properties. PMID- 1751675 TI - Myasthenia gravis (MG) treatment with immunoadsorbent columns. AB - We performed ten plasma perfusion (PP) treatments on eight patients affected by Myasthenia Gravis (MG) with high serum levels of autoantibodies against acetylcholine receptors (anti AChR-AB), and one PP treatment on a patient with MG of probable genetic origin and without specific antibodies. All patients (Osserman group III-IV) had undergone thymectomy and immunosuppressive therapy. Each patient received a treatment cycle of six PP sessions. Clinical conditions were assessed before and after the treatment with evaluation of muscular strength, ventilatory function, and electromyographic testing. Immunologic markers were tested before and after each PP. The patient without specific antibodies showed no improvement with PP and was excluded from our study. All the other patients showed continued improvement, with increased muscle strength and improved respiratory function. Four patients (follow-up 16-24 months) still maintain the clinical improvement; two, unexpectedly relapsed 11-12 months after PP, received a new treatment successfully (follow-up 9-10 month). PMID- 1751676 TI - Immunoadsorption with PH-350: as a beneficial therapy for acute Guillain-Barre syndrome. AB - The subjects here were patients (two males and a female) with the severe acute Guillain-Barre Syndrome admitted to our hospital between September 1987 and December 1988. One case was treated with a double filtration plasmapheresis and two cases were with a immunoadsorption. Of the two extracorponeal thrapeutical methods, the clinical efficacies seemed not to be different however biochemical and serological laboratory data showed prominent differences. For instance the large molecular substances in blood; immunoglobulins, coagulating factors and albumin were reduced in plasma levels by the double filtration plasmapheresis, but not or less by the immunoadsorption. Considering the expectable side effects of the two methods, it may say that the immunoadsorption should be applied as a beneficial extracorponeal method for the acute Guillain-Barre Syndrome. PMID- 1751677 TI - Clinical experience of double filtration plasmapheresis for drug refractory neurological diseases. AB - The effect of therapeutic double filtration plasmapheresis (DFPP) was clinically investigated for drug refractory neurological disorders. DFPP therapy was performed 181 times for 10 patients who were treated with medical therapy of steroid or immunosuppressive drugs without any improvement of their symptoms. After the induction of DFPP therapy the neuromuscular disturbances were soon ameliorated in 9 cases of them. After DFPP, serum levels of IgG, IgA or IgM were decreased as follows: IgG 0.53 +/- 0.16; IgA 0.60 +/- 0.11; IgM 0.59 +/- 0.09 (M +/- SD). After the DFPP therapy there was no relapse in improved 9 cases. But we could not regard the immunologic markers as the index of efficacy of DFPP. Because serum levels of IgG, IgA or IgM showed a tendency to decrease by using drugs, when we didn't observe any improvement of symptoms. These results suggest that DFPP is a beneficial therapy for neurological diseases who had no effect with drug therapy, however, serum concentrations of the immunologic markers were not necessarily correlated to the severity. PMID- 1751678 TI - Immunoadsorption and plasma exchange in multiple sclerosis: complement and plasma protein behaviour. AB - Three groups of patients suffering from acute attacks or progressive multiple sclerosis (MS) are under investigation. First results revealed remarkable clinical improvements of patients with acute attacks in the groups treated by therapeutic plasma exchange (TPE) and immunoadsorption (IA). Only slight or no improvements were seen in the patients of the control group treated only with steroids. Plasma protein levels (IgG, IgM, IgA, fibrinogen) were considerably reduced in patients of the TPE group after each treatment procedure as expected. The same holds true concerning the total hemolytic capacities (THC) of the complement of the classic (CP) and the alternative (AP) pathway. On the other hand in the IA group only slight decreases of plasma proteins (about 20%) were observed, but the behaviour of THC's were quite similar than those seen in the patients of the TPE group. The THC decreases in both groups can be explained by removal of all complement factors (TPE group) or by the adsorption of single factors (IA group) of both complement pathways according to earlier in vitro investigations. The THC decreases in patients of both groups suffering from acute MS attacks could mean an "antiinflammatory" effect and could--at least partially- contribute to the clinical improvements of these patients. PMID- 1751679 TI - LDL-apheresis and improvement in the coronary atherosclerosis of familial hypercholesterolemia--correlation of computerized quantitative coronary angiography with autopsy findings. AB - We have evaluated the effects of LDL-aphereses performed over 15 to 62 months, involving both Double Filtration Plasmapheresis (DFPP) and LDL Adsorbent Plasmapheresis (LAPP), for 5 patients with familial hypercholesterolemia (FH) (1; homozygous, and 4; heterozygous) using computer image analysis by coronary angiography, (CAG). Results by CAG showed that in homozygous FH, 9 (75%) of 12 segments demonstrated no progression, 2 (16.7%) segments showed regression, and only 1 (8.3%) segment showed progression. In heterozygous FH, 27 (81.8%) of 33 segments showed progression, and 6 (18.2%) segments showed regression. Aorto coronary bypass was beneficial with obtained patency in 13 (93%) of the 14 grafts. We also performed an autopsy on one patient, with heterozygous FH who died suddenly probably due to fibrillation. The patient had received long-term LDL apheresis for 6 years and 7 months and had shown angiographic regression. The pathological findings showed no typical or new atheroma, significant cicatrization in the thickened intima and an eccentric thickened wall lesion. The serial angiographic findings together with the pathological findings very clearly support the use of LDL-apheresis for producing "true" regression in coronary atherosclerosis in FH. PMID- 1751680 TI - Treatment of severe hypercholesterolaemia by LDL-apheresis. AB - The most severe forms of hypercholesterolaemia scarcely respond to diet and conventional drugs administration and need, therefore, alternative treatments. Terapeutic Plasma Exchange demonstrated an improved survival of subjects with Familial Hypercholesterolaemia (FH) in spite of its limitations. Semi-selective and selective techniques have been developed in order to remove LDL cholesterol alone. We studied the efficiency in LDL removal both of membrane filtration as of dextrane sulphate adsorption on 14 FH patients, performing 302 procedures. Cholesterol extraction with the different methods was in the range of 40-65%. Mean cholesterol level was reduced from 7% to 64% depending on the protocol used. The procedures were all performed on an outpatient basis. Side effects occurred rarely and were always of not serious degree. The short and the middle term clinical effects of LDL-Apheresis are then evaluated. PMID- 1751681 TI - An experimental study on selective elimination of beta 2-microglobulin using immunoadsorption method in patients with chronic renal failure. AB - We studied selective elimination of beta 2-microglobulin (beta 2-m) from plasma of patients with chronic renal failure (CRF) by using immunoadsorption method. Anti-human beta 2-m antibody of rabbit IgG was coated with cellulose beads, which were filled into a small-column. One gm of cellulose beads contains 5.0 mg of the protein of antibody. Five to 7 ml of plasma samples with 40 to 70 mg/l of beta 2 m were passed through the column at 1.0 ml/10 min and each effluent was then collected by 1.0 ml consecutively. Before and after passing through the column, beta 2-m and other plasma proteins were measured. Plasma beta 2-m concentrations in all the effluent fractions after passing through the column were greatly reduced to 1/100. But no other plasma protein components than beta 2-m varied in concentration. Neither Immune complex (IC) nor rabbit IgG was detected in any effluent fraction. These results indicate that selective and effective elimination of beta 2-m from plasma in patients with CRF was possible by using our method. In addition, since neither IC nor rabbit IgG was detected in the effluent, this method was considered to be clinically applicable. PMID- 1751682 TI - Sterile and endotoxin free dialysis fluid for hemodialysis. AB - As the quality of water in dialysis fluid varies considerably, and, in view of the fact that endotoxin or active derivates can cause acute and chronic side effects in patients under hemodialysis treatment, the dialysis fluid must be sterile and endotoxin-free. The predialyzer fluid in 20 hemodialysis patients was investigated. The bacterial loading was between 5/ml and 12,000/ml, the endotoxin concentration was high and extremely variable. Therefore we introduced the ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane before entering the dialyzer. All samples were free of bacteria, and the concentration of endotoxin was lower than the detectable limit. With this procedure we can obtain sterile dialysis fluid, which is endotoxin free. Our preliminary results showed that Interleukin-1 in the patients was significantly (p less than 0.005) lower under ultrafiltration of the dialysis fluid than without ultrafiltration. PMID- 1751684 TI - [Acute pancreatitis: a disease with 2 faces]. PMID- 1751683 TI - Increased concentrations of free light chain lambda in sera from chronic hemodialysis patients. AB - Serum levels of FLc were determined in 5 pre-HD CRF patients, 63 CRF patients receiving HD therapy, 15 CAPD and 40 healthy volunteers. The highest serum FLc concentration was observed in patients receiving HD. Concentrations of kappa- and lambda FLc were higher than normal in patients with CRF, and were about 4-fold and 1.8 fold greater than control values in HD patients, with a predominance of lambda chains. This HD-associated elevation of serum FLc strongly suggests a role for FLc in the etiology of light chain deposit disease and AL-amyloidosis. Lambda FLc and beta 2-m exhibited similar patterns of change in the serum during the course of HD therapy. Further studies may reveal other pathological conditions other than CRF in which these polypeptides may play a role. PMID- 1751685 TI - [The parenteral drug addict in the emergency service]. AB - Clinical and epidemiological features of intravenous drug addicts (IVDA), who attended the emergency department between 1984 and 1988, were studied. The number of cases treated over these 4 years had increased three-fold (256 vs 724). The median age had increased by 3 years (p less than 0.01). The sex ratio had not changed. A third of the cases knew that they were HIV-seropositive in 1988. The main reason for consultation in 1984 was overdosage and in 1988 it was fever. The rate of admission was similar in both years (around 21%). There was a significant increase in admissions caused by respiratory diseases in 1988 (p less than 0.0001) and a significant decrease of admissions caused by overdosage (p less than 0.001). PMID- 1751686 TI - [The bone manifestations in 94 cases of sarcoidosis]. AB - 94 patients diagnosed as having sarcoidosis were studied in Galicia in order to evaluate the frequency of bone manifestations, as well as to analyse the clinical and radiological features. Bone lesions were found in 10 patients (10.6%) with a median age of 47.4 years, the predominant sex being female in this group (70%). The lesions were of two types: a) osteolytic on metacarpal (4 cases), nasal bones (1 case), sacrum (1 case), femur (1 case); b) osteosclerosis on femur and fibula (1 case), acrosclerosis (3 cases), metacarpal (1 case). The first lesions were associated to chronic types of sarcoidosis with skin and lung involvements. The second lesions were associated to a sub-acute type of Lofgren. We highlight the behaviour of both types of bone lesions and comment on the physiopathology of the sclerotic lesions. PMID- 1751687 TI - [A mortality study in the Internal Medicine Emergency Service of October 12 Hospital during 1989]. AB - 152,902 patients were attended at the Emergency Department of "12 de Octubre" Hospital during 1989; 48,701 of them were seen in the Internal Medicine area. 196 dead, 164 case histories were selected in order to fulfil the protocol. Several variants were analysed, such as age, sex, diagnosis, time spent at the hospital, quality of life, date, etc. 53.6% were male; the median age was 73 years and the overall median age of all patients seen was 55.9 years. Median Karnovsky was 52.50% of the patients died during their first 5 hours at the Emergency Department. The most frequent diagnoses for the area were neurological, followed by cardiovascular, oncological, digestive, etc. The most frequent diseases observed were cerebrovascular accident, cardiac insufficiency and acute infarction, oncological cases and death on arrival. Mortality was higher in winter. On the whole, mortality was higher in oncology patients followed way behind by neurology digestive and cardiovascular patients. PMID- 1751688 TI - [Insulin-dependent diabetes mellitus and arterial hypertension]. AB - Blood pressure variations of 30 insulin-dependent diabetic patients free of complications, and aged between 14-35 years have been studies, comparing their results to those from a control group formed by healthy person of the same age and physical features. Median systolic pressure of diabetic population was 120 +/ 11.07, compared to 112.90 +/- 11.31 from control group. The median diastolic pressure of diabetic population was 76.76 +/- 10.12 and 67.40 +/- 7.94 of the control group. A significant difference on systolic (p less than 0.05) and diastolic (p less than 0.001) pressures were observed in insulin-dependent diabetic patient comparing their results to those from the control group. PMID- 1751689 TI - [Splenic artery aneurysm. Apropos 3 cases]. AB - 3 cases of aneurysm of the splenic artery are presented. The incidence of this disease in the general population is not particularly low, however, it is not often diagnosed as it is not symptomatic. 2 of our patients were admitted because of abdominal pain, one of them with acute abdomen and shock and the other had two periods of symptoms with a nonsymptomatic interval between them; both patients had aneurysm resection and splenectomy. The third patient was non-symptomatic and the aneurysm was discovered due to a ring-like calcification. We highlight the value of a contrast CT scan in order to diagnose splenic artery aneurysms. PMID- 1751690 TI - [Necrotizing myelopathy associated with neoplasia. A clinico-pathological study of 2 cases and a review of the literature]. AB - Two cases of necrotic myelopathy are presented. This is a very rare paraneoplasic syndrome. One patient had clear cell renal carcinoma and other had lymphatic metastasis of malignant melanoma without filiation of the primary tumor. The complete spinal study (MNR, CT, myelography) proved normal. Diagnosis is possible when all other causes of spinal disease have been discarded. Nowadays, it is possible to diagnose this disease premortem. The international literature reviewed showed 31 cases published since 1903, associated mainly to malignant diseases such as lymphomas, lung cancer, renal carcinoma, breast cancer, leukemias, etc. The differential diagnosis appears in the comments, as well as the presentation and evolution of the cases described up until now. PMID- 1751691 TI - [Lupus myopathy refractory to steroid treatment]. AB - A 58-year-old patient with lupus erythematosus (LE) who needed treatment with azathioprine, due to resistant myopathy to steroids, is presented. Clinical and histological features, as well as therapy, are discussed. PMID- 1751692 TI - [Plasmacytoma of the thyroid. A review apropos a case]. AB - Isolated presentation of outer bone marrow plasmatic cell neoplasia are non frequent (less than 10% of all plasmacytomas). Thyroid gland involvement is rarely described. A case where immunohistochemistry confirmed the monoclonal type of proliferative cell is presented. Clinical, pathological and diagnosis criteria, as well as response to treatment, are reviewed. PMID- 1751693 TI - [Substances harmful for the gastric mucosa]. AB - Gastroduodenal mucosa has a self-defense capacity against a wide range of potentially harmful exogenous and endogenous agents. It has been proven that certain diet compounds damage gastric mucosa, which explains--at lest partially- the regional variations in the incidence of peptic ulcer. Ethanol blocks the defense mechanisms of gastric mucosa and induces the onset of acute lesions, but there is no definite proof to show that ethanol ingestion helps produce the onset of peptic ulcer. It has been confirmed that tobacco negatively affects the healing and relapse of ulcers. From an epidemiological point of view, the controversy of the relationship between tobacco abuse and peptic ulcer genesis is still ongoing. Non-steroid anti-inflammatory non-acid soluble produces lesions acute and chronic) in gastroduodenal mucosa. They can reactivate old lesions and increased the risk of complications. Aspirin is the most harmful compound in this pharmacologic group. Paracetamol is the compound which has the safest spectrum. The harmfulness of steroids is still being discussed, however, it is accepted that they have a rapid effect on gastric mucosa in relation to dosage and duration of treatment. PMID- 1751694 TI - [An update on the management of Raynaud's phenomenon]. AB - Basic knowledge of clinical management of Raynaud's phenomenon was established and reviewed. Body protection against cold weather and the avoiding of all activities which cause the setting off of the ischemic episodic trigger are the first step in the therapy for this type of patient. Medical treatment includes vasoactive drugs and other drugs which act against the different factors such as plasmapheresis, sympathectomy and electric neurostimulation must be reserved for patients with severe vascular symptoms. PMID- 1751695 TI - [Acute kidney failure (AKF) and hemolysis secondary to accidental discontinuous treatment with rifampicin]. PMID- 1751696 TI - [The incorrect use of inhalers]. PMID- 1751697 TI - [The indication for treatment with home oxygen therapy after the hospital discharge]. PMID- 1751698 TI - [Solitary bone metastases of unknown origin. Apropos 15 cases]. PMID- 1751699 TI - [Rhabdomyolysis, Salmonella enteritidis infection and the bibliography]. PMID- 1751700 TI - [Chickenpox and acute pericarditis in a patient with HIV infection]. PMID- 1751701 TI - [Still's disease in the adult: suspect it from the analysis and minor symptoms]. PMID- 1751702 TI - [Pneumonia caused by Bordetella bronchiseptica in a patient with Crohn's disease]. PMID- 1751703 TI - [Chronic massive idiopathic pericardial effusion]. PMID- 1751704 TI - [The ethical aspects of clinical trials in primary care]. PMID- 1751705 TI - [Consensus conferences in Spain and their practical application]. PMID- 1751706 TI - [Consensus for the Control of Arterial Hypertension in Spain. Madrid, 1989]. PMID- 1751707 TI - [The satisfaction of the primary care consumer: a comparison between distinct models of care]. AB - The results of a questionnaire about satisfaction in the users of an urban health area of the city of Alicante, where the traditional model of primary care (the clinic, C), the new model (the health center, HC) and private practice (P) coexist are reported. The questionnaires were administered by staff unrelated with the health center. In general, satisfaction was significantly greater (p = 0.001) in users of HC and P than in C users. no significant difference was found between HC and P. The specific satisfaction was also greater (p less than 0.05) for all services in HC than in C: General practice (GP), nursing care (N), pediatrics (PED), and administration-information (ADMON). The general satisfaction did not correlate with sociodemographic variables; it was weakly correlated with the service use variables, and was clearly correlated (p less than 0.001) with the specific satisfaction with the use of services such as GP (r = 0.57), PED (r = 0.49), ADMON (r = 0.56), and N (r = 0.58). PMID- 1751708 TI - [Community-acquired urinary infection: the in vitro activity of trimethoprim and cotrimoxazole]. AB - To evaluate the in vitro sensitivities of trimetoprim (TMP) in our area and to compare them with those to co-trimoxazole (CMX) a prospective study was carried out in females with uncomplicated lower urinary tract infection (UCLUTI), as a preliminary step for the possible use of a monodose of TMP in these patients. Fifty-five cases of UCLUTI were included. Escherichia coli was the predominating organism (70.9%). The general sensitivity to CMX was 80% and that to TMP 76.4%. The E. coli sensitivity to CMX was 79.5%, and 76.9% to TMP. The difference in the sensitivities to both antimicrobials was not statistically significant (p = 0.5). The routine introduction of TMP in the antibiogram would permit to evaluate the resistance to this antimicrobial in each area and, on the basis of the results, to assess the effectiveness of TMP in the treatment of UCLUTI. PMID- 1751709 TI - [The effect of family factors on school retardation in the Cartuja quarter of Granada]. AB - The possible influence of the family on school retardation was evaluated in the Cartuja quarter in Granada for the academic term 1988-89. The study was performed on 258 schoolchildren of the 7th and 8th primary courses in the four public schools from the quarter. Data were collected with a questionnaire including the following variables: school retardation, sex, number of siblings, ordinal number among siblings, educational level of the parents, and work of the mother outside the household. To evaluate family function the APGAR questionnaire was used. A remarkably high (45.7%) school retardation was found, higher than that in the rest of Spain. School retardation cannot be related with the family dysfunction detected by the familial APGAR. It was related, rather, with the child's sex, the educational level of the mother, the number of siblings and the ordinal place of the child among them. PMID- 1751710 TI - [The results of the introduction of a protocol of preventive activities in a primary care center]. AB - A sample of 360 people was analyzed. They had received the protocol of preventive activities of the "Unitat Docent de Medicina Familiar i Comunitaria de Barcelona" during 1989. The results of those activities directed to the prevention of cardiovascular risk and to the detection of excessive alcohol intake are reported, as they are those with the easiest and widest implementation. Overall results include hypercholesterolemia in 43.9%, abnormal blood pressure in 10.5%, a rate of smokers of 31.7%, 7.7% with an excessive alcohol intake, and 51.9% of obese individuals. The results are also shown by age and sex groups. In the discussion, the results are compared with those expected for our population. It is concluded that preventive measures should be encouraged by primary health are teams. PMID- 1751711 TI - [The incidence and clinical presentation of tuberculosis in HIV-positive patients]. AB - To evaluate the features of tuberculous infection in HIV+ patients from our area we reviewed the 50 cases of seropositive patients admitted to a provincial hospital from 1985 to June 1989. TB was diagnosed in 18 of the 50 patients; mean patient age was 27 years, with a male predominance. PDA was the major risk practice. The most common localization were lymph nodes; 95% had fever and weight loss and 39% had nightly perspiration and cough; cervical lymphadenopathy and hepatosplenomegaly were found in more than 50%. Tuberculin skin test was negative in 75% of cases. The diagnosis of TB represented the diagnosis of AIDS for 66% of patients. 25 of the 50 seropositive patients met the criteria for AIDS, and 68% of these had TB. TB is a common infection in HIV+ patients from our area, and it is the first cause of the diagnosis of AIDS. The index of suspicion of TB in these patients should be high, as clinical features are often nonspecific. However, it is preventable and curable superinfection. PMID- 1751712 TI - [The Melkersson-Rosenthal syndrome. Apropos 2 cases]. AB - Melkersson-Rosenthal syndrome is classically defined as facial palsy, oedema facial and plication of the tongue, constituting one rare cause of facial palsy. The primary care physician must include this syndrome in the differential diagnosis of Bell's palsy. We report two cases of this syndrome, one in a young man, another in a 56 aged woman, and also a succinct literature review. PMID- 1751713 TI - [Reflections on the somatization concept]. PMID- 1751714 TI - [Radiology of the colon]. PMID- 1751715 TI - [The medical consultation and health promotion]. PMID- 1751716 TI - [The immune status vis-a-vis Toxoplasma of the pregnant population of Valladolid]. PMID- 1751717 TI - [The suitability of the use of injectable antibiotics in primary care]. PMID- 1751718 TI - [Epidemiological survey: apropos a case of trichinosis]. PMID- 1751719 TI - [Atopy and IgA deficiency]. PMID- 1751720 TI - [Vaccination and hepatitis B: only for groups at risk?]. PMID- 1751722 TI - [Temporal arteritis]. PMID- 1751721 TI - [Enalapril-induced cough]. PMID- 1751723 TI - [The Family Medicine Program and AIDS]. PMID- 1751724 TI - [The terminal patient in primary care]. PMID- 1751725 TI - [Health for all and research on primary care]. PMID- 1751726 TI - [The epidemiology of breast feeding: its prevalence and duration]. PMID- 1751727 TI - [A prospective study of programmed nursing consultation in an urban health center]. AB - A study of the programmed nurse clinic in a health center was carried out to evaluate its different health care activities, the time consumed in them, the type of patients cared for, and the mechanism of organization of the clinic. A remarkable finding was a high number of daily appointments (11.8 persons), with an excellent rate of compliance with the appointment (89.3%). It was found that most of the diseases cared for in the nurse clinic were those most commonly managed with a protocol design in primary care: hypertension (34.1%), diabetes (6.9%), hyperlipoproteinemia (9%) and obesity (12.8%). Other parameters were evaluated, such as mean time per visit, which was predominantly between five and ten minutes, or activities during the visits, with a clear predominance of the clinical protocols. There was a remarkably high efficiency of the nursing staff, with a low rate of referral to the medical clinic (6.9%). We conclude that nurse clinics play an important role in the health centers, as the only possible mechanism to guarantee the correct fulfillment of the different programs. This requires a definite constant physical space for a given minimal period of time of about 2 hours per day. PMID- 1751728 TI - [The diagnosis of diabetes mellitus in epidemiological studies]. AB - The aim of the present study was to evaluate the relative usefulness of some of the diagnostic methods used to estimate the prevalence of diabetes mellitus in epidemiological studies. A cross-sectional descriptive study with multistage stratified sampling was designed. A personal interview, a capillary baseline glycemia and a OGTT were carried out. The medical records and the use of antidiabetic drugs and self-control products were also evaluated. The prevalences obtained with these methods were: Medical records = 1.31%, personal interview = 7.91%, use of drugs = 1.93%, self-control products = 1.05%, capillary baseline glycemia greater than or equal to 120 mg/dl = 4.04%, OGTT with WHO criteria = 5.62%. Using OGTT as a reference, the diagnostic test with the greatest overall value was capillary baseline glycemia equal to or higher than 120 mg/dl. We think that, as a whole, the election of one method or another will depend on both the precise aim of the study and the type of design and the cost that can be sustained. PMID- 1751729 TI - [An analysis of the referrals to specialist consultations made in a health center]. AB - The study of referrals from primary care areas permits the evaluation of health care in this level and reveals the educational requirements of the specialists in family medicine. Between January and April 1988 a prospective study was carried out to evaluate the referrals to the second level of care in the health center V Centenario. In 27,657 visits 1,906 referrals to the different specialties were ordered, which represents a rate of 6.89%. The most commonly consulted specialties were gynecology (18.94% of the overall referrals), ophthalmology (18.04%) and traumatology (16.10%). Psychiatry (1.41%), neurology (1.31%) and endocrinology (1.41%) were the specialties with the lowest referral rates. We compared our results with those from other authors and we have calculated what influence would be exerted on the second level of care if all primary care physicians had similar referral rates to those obtained in our center. PMID- 1751730 TI - [Cardiovascular risk factors in the working population of Alicante]. AB - The aim of the present study was to evaluate the prevalence of certain cardiovascular risk factors in the population of Asepeyo-Elche. The study sample was a working population of 697 persons (71.8% males and 28.2% females) with ages ranging from 15 to 65 years (mean age 34.7 +/- 13.2 years), seen during the first 6 months of 1990 in the health care center of Asepeyo-Elche. The evaluated cardiovascular risk factors and their prevalence rates were: hypertension (14.2%), hypercholesterolemia (18.5%), smoking (52.5%), hyperglycemia (3.5%), obesity (28.2%) and sedentariness (80.3%). We conclude that in our working population the prevalence rates of some cardiovascular risk factors are high and that intervention programs to modify the diet and lifestyle are mandatory to prevent the pathogenetic consequences of these factors. PMID- 1751731 TI - [The current concepts of drugs, drug dependencies and the drug-dependent]. PMID- 1751732 TI - [Intravenous urography]. PMID- 1751733 TI - [The efficacy of systematic vaccinations in Spain]. PMID- 1751734 TI - [Captopril and the liver]. PMID- 1751735 TI - [Another case of diabetes insipidus diagnosed in primary care]. PMID- 1751736 TI - [Inaccuracies in bibliographic citations: an obstacle for the quality of our scientific publications]. PMID- 1751737 TI - [Nitrendipine and nycturia]. PMID- 1751738 TI - [The attitudes on the part of specialists in family and community medicine respecting their specialty. A failure of the educational system?]. PMID- 1751739 TI - [The recording of mental pathology in the clinical history at a rural health center]. PMID- 1751740 TI - [Urinary infections at a health center: the microorganisms and antibiotic resistance]. PMID- 1751741 TI - [Imported diseases and immigration medicine]. PMID- 1751742 TI - [The legal possibilities for action in the health inspection of public eating establishments]. AB - This study, based upon the Spanish legal framework and upon the experience of the authors, is intended to establish the legal procedures for action when a sanitary inspector finds himself in the situation where he observes that a public establishment is infringing some hygiene or sanitary regulation which may carry a health risk of varying seriousness. Possibilities for action are outlined, depending on the urgency and seriousness of the situation, as well as indicating who is responsible for the application of the law in each case. The legal possibilities for action are: the closure of the establishment, a warning, and institution of penal proceedings. Finally some suggestions are made as to the method of carrying out such inspections. PMID- 1751743 TI - [The evaluation of noncompliance in an anti-influenza vaccination program]. AB - The article presents an evaluation of an anti-influenza vaccination programme in a population at risk, with a special study of the general characteristics of the group of non-complying patients, and the possible relation of these characteristics with their conduct. Moreover, a study was made of the possible motives for not complying with the vaccination programme by means of a survey carried out by post and telephone in a representative sample of 108 individuals. A 34.77% of the registered population did not receive the anti-influenza vaccine, corresponding largely with the youngest age group (15 to 44 years) and there were no significant differences determined by sex or risk factor or doctor. A positive response was received from 75% of those surveyed, and the basic conclusions drawn were a low proportion of information error attributable to the programme (2.94%), and patient refusal as the principal cause of non-compliance (54.41%), followed by "other reasons" (hospitalisation, absence from home, etc.) (32.35%). The strategies that may be followed in the face of this problem require definition of the group of non-compliers, further understanding of the motives for their conduct, and educational measures to change their attitude. 95.9%). Incidence of hypertension and hyperlipemia was 56.2% and 47.3%. Late vascular events varied between 2.6% (nephropathy) and 19.5% (retinopathy). A total of 101 patients (44.6%) were unaware of the existence of diabetic health education programmes. Moreover, 68 (30.3%) declared that they had never received any previous information about their diabetes. Practical skills were evaluated on an individual basis. PMID- 1751744 TI - [Mental malaise in health professionals: an approach to its study]. AB - A study was made of the incidence of psychiatric malaise among health workers in the health area of La Axarquia, in the province of Malaga. Goldberg's General Health Questionnaire (GHQ, 28 items) was applied to the sample population (n = 137), and the differences obtained are discussed in relation to social and job related variables. The occurrence of psychiatric malaise among the whole sample was 29.85%, with significant differences among those above the cutoff and place of work (hospital), sex (women), tobacco habit (smokers), and pleasantness of work situation (not pleasant). There were no significant differences among those above the cutoff and profession (although higher scores were recorded among administrative personnel), nor according to contractual situation (although higher scores were recorded among contracted staff). The study concludes with a series of measures aimed at early prevention and detection of symptoms of psychiatric maladjustment within the working environment. PMID- 1751745 TI - [The management of minor burns in primary care]. PMID- 1751746 TI - [Retrograde cystourethrography]. PMID- 1751747 TI - [Semiexperimental and experimental design and evaluative research]. PMID- 1751748 TI - [Resources for exploring autonomic neuropathy in diabetes]. PMID- 1751749 TI - [Dextrocardia with complete situs inversus]. PMID- 1751750 TI - [The detection of cardiovascular risk factors via a program of preventive activities]. PMID- 1751751 TI - [An evaluation of the structural characteristics of local consultation offices in a rural health area]. PMID- 1751752 TI - [Severe hyponatremia: an infrequent but serious complication of thiazide diuretics]. PMID- 1751753 TI - [Castleman's disease]. PMID- 1751754 TI - Priming of phagocytes by cytokines and water-soluble products of lipid peroxidation. AB - It is well known that during certain pathological processes phagocytes acquire the ability to generate activated oxygen species during phagocytosis. The priming of phagocytes by cytokines and water-soluble products of lipid peroxidation (LPO) is described. Preincubation of human polymorphonuclear leukocytes (PMNL) with the water-soluble products of LPO or oxidised liposomes for 15-20 min at 37 degrees C enhanced their functional activity when they were stimulated by opsonised zymosan or latex particles. There was a 2-3-fold increase in luminol-dependent chemiluminescence response of cells stimulated in this way, and an increase in Fc receptor expression on the PMNL surface. An endogenous cytokine alone did not activate the phagocytes for an oxidative burst response, but preincubation of murine peritoneal macrophages (MP) and human PMNL with cytokines (molecular mass 20-30 kDa) for 3-48 h at 37 degrees C enhanced the cell chemiluminescence response to opsonised zymosan by a factor of 5-9 for MP and a factor of 2-3 for PMNL. Treatment of phagocytes with the cytokine complex also increased other effector functions of the phagocytes such as tumouricidal activity, phagocytosis, secretion of interleukin-1, and antiparasitic activity. The protein synthesis inhibitor cycloheximide abolished cytokine-induced priming of MP (but not of PMNL). The mechanisms of short-term and prolonged priming of the two types of phagocytes (MP and PMNL) are discussed. PMID- 1751755 TI - The effect of tryptophan on the phenobarbital-mediated induction of cytochrome P 450 in rat liver. The role of tryptophan 2,3-dioxygenase. AB - The effect of intraperitoneal administration of phenobarbital (80 mg kg-1 body weight) and tryptophan (200 mg kg-1 body weight), separately or in combination, on the microsomal content of cytochrome P-450 and the activity of tryptophan 2,3 dioxygenase (EC 1.13.11.11) in Wistar rat liver was determined at different time intervals after injection. There was an increase in the amount of cytochrome P 450 within 12 h of administration of a single dose of phenobarbital which was maintained over the next 12 h. Tryptophan had no effect on the amount of cytochrome P-450, but administration of tryptophan in combination with phenobarbital blocked the increase that was found after administration of phenobarbital alone. Both phenobarbital and tryptophan increased tryptophan 2,3 dioxygenase activity (total enzyme and holoenzyme) but had different effects on the rate of activation and the degree of saturation of the enzyme with haem. Administration of tryptophan and phenobarbital in combination invoked the same effect as tryptophan alone. Significant activation of the holoenzyme was found, when tryptophan was administered 2 h after phenobarbital administration. It is proposed that combined administration of phenobarbital and tryptophan leads to substrate stabilisation of tryptophan 2,3-dioxygenase, and that this is accompanied by the binding of the newly synthesised haem, thus making haem unavailable for formation of cytochrome P-450. PMID- 1751756 TI - Intracellular factors determining the deposition of glycogen. The role of gluconeogenesis. AB - The interrelationship between glycogen biosynthesis and do novo glucose formation in rats was studied by determining the oxaloacetic acid, ATP, and glycogen levels in the tissues of healthy starved rats and during the growth of transplantable hepatomas with different rates of growth. From the results obtained it was proposed that glycogen biosynthesis and de novo glucose formation are mutually enhanced and coupled processes. The validity of this conclusion was confirmed by in vitro model experiments involving the use of isolated-liver perfusion. Results of a multiple regression analysis indicated that the efficiency of gluconeogenesis and glycogen deposition is determined by the supply of oxygen to the liver, by the oxaloacetic acid content of this organ, and also by the degree of reduction of the glucose precursor. It was also shown that the ability of glucocorticoids and glucagon to enhance gluconeogenesis is dependent on the supply of oxygen to the liver. From the results of this in vivo and in vitro comparative study it is concluded that deposition of glycogen in the liver and possibly also in the brain is determined by the efficiency of gluconeogenesis. PMID- 1751757 TI - The study of fibrin polymerization with monoclonal antibodies. AB - Three kinds of monoclonal antibody (Mab) of different specificity have been obtained against the N-terminal disulphide knots of fibrinogen and fibrin. Their effects on different phases of fibrin polymerization have been studied. These antibodies were shown to be directed against different epitopes of the B beta(1 53) fragment of the fibrinogen molecule. The different Mab had different effects both on the rate of protofibril lateral aggregation and on the final turbidity of fibrin clots. The Mab were of three specificities: (1) those from clone 2d-2a inhibited the rate of lateral aggregation of protofibrils and decreased the turbidity of the final clot; (2) those from clone B-4C accelerated the polymerization step but did not affect clot turbidity: and (3) those from clone D IB did not have any effect on either fibrin polymerization or final clot turbidity. The localization of the epitopes recognized by all three kinds of Mab and analysis of our own data and those of others allow us to conclude that one of the active loci involved in protofibril lateral association is situated in the B beta(15-53) fragment of the fibrinogen molecule. Fibrinopeptide B does not need to be split off for this site to function. Fibrin polymerization can occur when one of the two sites of protofibril lateral aggregation in dimeric fibrin molecules is blocked by Mab, and the final clot turbidity is then reduced. The splitting off of one of the two fibrinopeptides B in fibrinogen molecules by thrombin can take place even when the second B beta(Arg14-Gly15) bond is blocked by an antibody molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751758 TI - The effect of the structure of the terminal regions of the hepatitis B virus gene C polypeptide on the formation of core antigen (HBcAg) particles. AB - A series of plasmids encoding native and modified sequences of the hepatitis B virus core antigen (HBcAg) was created. Analysis of the products generated by expression of the plasmid genomes in Escherichia coli showed that a polypeptide with primary structure identical to that deduced for native HBcAg forms particles in the bacterial cells which are indistinguishable from the native nucleocapsids in morphological and antigenic properties. Removal of the thirty-nine C-terminal amino acids which form a protamine-like domain caused insignificant impairment of the particle-forming process. Modification of the N-terminal region of the polypeptide showed that at least part of the structural determinant governing particle formation is localised between amino acid residues 3 and 11. When the plasmid genes were expressed in an E. coli cell-free transcription - translation system, polypeptides devoid of ten to twenty N-terminal amino acids were formed in addition to the full-length products. From the results obtained it is proposed that a protease digestion site situated within the region containing amino acid residues 10 - 20 plays a role in the formation of the HBe antigen. PMID- 1751759 TI - Interhemispheric asymmetry of EEG coherence as a reflection of different functional states of the human brain. AB - EEG coherence analysis was used to study aspects of the synchronisation of electrical processes in the left and right cerebral hemispheres of right-handed and left-handed healthy subjects in a state of calm wakefulness. Right-handed subjects showed a greater coherence in the left hemisphere and left-handed subjects in the right hemisphere. There were also differences between right handed and left-handed subjects in the regional profiles of interhemispheric asymmetry and in the interhemispheric asymmetry of individual spectral bands. These differences may reflect variations in the involvement of cortical and subcortical cerebral structures in the formation of the hemispheric specificity. Changes in interhemispheric coherence with the onset of drowsiness were also observed. This suggests that changes in the interconnections of neural networks are also involved in changes in arousal. Certain characteristic regional interhemispheric asymmetry patterns and asymmetries in the spectral bands appear to be necessary for normal human brain function. PMID- 1751760 TI - Analysis of the fine structure of the antigenic determinants of the transmembrane protein in the HIV coat with chemically modified synthetic peptides. AB - The amino acids involved in IgG reactivity to four HIV-1 gp41 overlapping synthetic peptides from the sequence 584-624 have been determined by a method based on the chemical modification of trifunctional amino acids, especially the acetylation of the amino groups of the lysine residues at pH 8-9. The reactivities of the sera from HIV-infected individuals and gp41-specific human Mab were studied with the overlapping peptides and their modified forms in indirect and competitive ELISA. Peptides 584-602 and 609-624 (CN-185) reacted with 88% of HIV-positive sera; the highest diagnostic significance (100%) was found with peptides 584-611 (AS-551) and 603-624 (CN-191). Acetylation resulted in a 10%-15% decrease in peptide reactivity. Moreover the concentration at which 50% inhibition occurred was 1.5 x 10(-6) M for unmodified AS-551 compared with 1.5 x 10(-5) M for the modified peptide. Circular dichroism spectra showed that acetylation did not alter the conformation of these peptides. Coupling of peptide AS-551 to a protein carrier at pH 6.5-7.0 did not affect the immunoreactivity of this peptide. Mab against human gp41 reacted with peptide 603-624 (CN-191). The concentration of this peptide necessary for 50% inhibition of Mab binding was 5.2 x 10(-6) M. It is concluded from the epitope mapping of the Mab that the antigenic determinant lies within the 603-609 fragment. Lys-608 appears to play a crucial role in the interaction with human HIVc-Mab. PMID- 1751761 TI - HIV-1 gag proteins in virions and in infected cell fractions. AB - The relation of the initial products of the HIV-1 gag gene to the final products was determined in virus samples and cell fractions of infected H9 and Jurkat-tat cell cultures. The proteins were identified by immunoblotting with pooled sera from AIDS patients or monoclonal antibodies. The proportion in the virions of gag precursor proteins and the products of their proteolytic cleavage varied according to the maturity of the virus particles as determined by electron microscopy. The distribution of viral gag proteins in the cell fractions was determined 2, 4, and 24 h after infection. Treatment of cells with cycloheximide to block de novo protein synthesis did not significantly affect the results. Gag proteins containing the N terminus of the precursor p55 (including p55, the intermediate precursors p41(45) and p39, and mature protein p17) were found in the cell nuclei up to 24 h after infection. The major core protein p24 was located in the cytoplasmic fraction. These data strongly suggest that gag precursors from the p55 N terminus and the matrix protein p17 enter the infected cell separately from the major core protein p24, or become separated from it in the cytoplasm. PMID- 1751762 TI - Diet-induced hypercholesterolaemia in the rabbit. AB - Intraspecies variation in diet-induced hypercholesterolaemia in rabbits, simulating atherosclerosis, was studied. The chinchilla rabbit population examined contained several subpopulations, as indicated by polymodal forms of histograms of plasma cholesterol levels. This finding indicates that the inclusion of subpopulations in an investigation can lead to erroneous conclusions, and that subpopulations should be identified before such work is undertaken. The relationship between the molar cholesterol/phospholipid ratio in rabbit erythrocyte membranes and the plasma cholesterol level in experimental atherosclerosis was also studied. A correlation was evident only over the range of 1-5 g cholesterol per litre of plasma. PMID- 1751763 TI - Karyological approach to the identification of true cell lines susceptible to the human immunodeficiency virus (HIV). AB - A karyological analysis of twenty-two variants of eight cell lines, which differed in their susceptibility to the human immunodeficiency virus (HIV) and which had been obtained from different sources, was carried out by means of differential chromosome staining for G and C bands. The karyotypes of eight T lymphoblastoid cell lines were identified, including five (MT-4, Molt-3, CEM, H 9, and Hut-78) not previously studied by cytogenetic methods. Karyotyping confirmed the identity of seventeen variants of the eight cell lines, and five variants of four lines were found to be misidentified. Comparative analysis of the cytogenetic characteristics of the three CEM-line variants demonstrates the need for karyotype evaluation in the course of in vitro cell cultivation. Fourteen identical marker chromosomes were revealed in H-9 and Hut-78 cell karyotypes, confirming the common origin of these two lines. It was found that the cells of the HIV-susceptible lines had a tendency to undergo polyploidisation both during the initial stages after isolation and in the course of cultivation. PMID- 1751764 TI - Region of hepatitis B virus DNA with a homology to the yeast ARS replication enhancer. AB - A computer analysis of the primary sequence of hepatitis B virus (HBV) subtype ayw DNA, cloned within the pVG2 recombinant plasmid, which raises its stability in Saccharomyces cerevisiae transformants, was performed. This revealed that the structure of the HBV DNA has: two bends in the termination regions of the HBs and HBc genes, and multiple sequences with a high degree of homology to the ARS (autonomously replicating sequence) core consensus in this region of the HBs gene. DNA fragments from the HBs region (330 bp) and from the HBc region (378 bp) have an abnormal electrophoretic mobility in 8% polyacrylamide gels. The similarity of the structural motifs in the stop-region of HBs gene with the B domain of the S. cerevisiae ARS element is discussed. PMID- 1751765 TI - Neural correlate of mental error detection in the human brain cortex. AB - The use of long-term intracerebral electrodes combined with advances in stereotaxic neurosurgery and a complex multimethodological approach to brain research has made possible a study of the neurophysiological mechanisms of higher mental functions in the course of diagnosis and/or treatment of some chronic cerebral diseases. Investigations in which both local oxygen tension and neuronal impulse activity were recorded while the patients were performing psychological tasks have revealed selective responses in some neuronal populations of the thalamus and of the striopallidal complex, which occur only during erroneous task performance. So-called 'error detector' neurons were also found in the perirolandic and parietotemporal regions of the human brain cortex. PMID- 1751766 TI - Influence of native and modified exogenous alcohol dehydrogenase on alcohol consumption in rats. AB - The effect of native alcohol dehydrogenase (ADH) and ADH modified by polyethylene glycol on alcohol consumption and certain other behavioural parameters in rats were studied. Intravenous injection of native heterologous ADH significantly suppressed alcohol consumption between the 10th and 15th days after injection with a duration of the effect of 40 days or more. During this period, a low but reliable production of anti-ADH antibodies occurred. ADH modified by covalent attachment of polyethylene glycol did not give these results. Native ADH and ADH modified by polyethylene glycol caused enhanced nociception and active avoidance formation. PMID- 1751767 TI - Individual-specific patterns of human variable genomic regions detected by a DNA probe from the HIV-1 env gene. AB - It was postulated that similar genetic elements that are 'hot spots' for genetic variation might exist in both the HIV-1 and the human genome. To test this possibility a short repeated sequence from a region of variability in the HIV-1 glycoprotein (env) gene was amplified and used as a probe for blot hybridization with human genome DNA. Human genomic regions were hybridized and characterized by a set of polymorphic restriction DNA fragments. The pattern of the restriction fragments was individual specific. Thus a DNA probe from the HIV-1 env gene can serve as a genetic marker for hybridization with human genome regions and for the identification of individuals. PMID- 1751768 TI - A scheme for the testing and quality control of medicinal immunobiological preparations in the USSR. PMID- 1751769 TI - International symposium on 'Regulation and clinical importance of immunoglobulin E'. PMID- 1751770 TI - Michel Mandel 65. PMID- 1751771 TI - Molecular characterisation of kappa- and lambda-carrageenan by gel permeation chromatography, light scattering, sedimentation analysis and osmometry. AB - Gel permeation chromatography, in conjunction with a double detection system involving a low angle laser light scattering apparatus (LALLS) and a refractive index monitoring device (RI), has been used to obtain both the molecular weight and the molecular weight distribution of sodium salts of kappa-carrageenan and lambda-carrageenan in saline solutions. The results, Mw and Mn, are in excellent agreement with independent determinations of molar mass based on static light scattering experiments, sedimentation-diffusion analysis and osmometry. The relevance of the data is discussed with respect to current problems in carrageenan research. PMID- 1751772 TI - Solution and gelling properties of polysaccharide polyelectrolytes. AB - Attention is focussed on the special class of polysaccharide polyelectrolytes belonging to the family of the microbial polysaccharides. But a few exceptions, these are high molecular weight water- soluble polycarboxylates with complex, regular structures. Complexity and regularity in primary structure--two features normally not shared by other polysaccharides of either vegetal or animal origin- quite naturally entail unique conformational propensities, special physico chemical properties in bulk and in solution and, as a consequence, make these biopolymers of particular interest from both a basic research and an industrial standpoint. What is outlined in this presentation should demonstrate that for many exocellular microbial polycarboxylates the solution properties are, as expected, dictated by the conformation assumed by the polyelectrolytic chains which, in turn, are governed by several free energy terms in particular stemming from specific solvent-chain interactions, among which the coulombic contribution may play a minor role. PMID- 1751773 TI - Polyelectrolytes at the endothelial cell surface. AB - It is recalled that the tension in a stretched polyelectrolyte chain mechanically compensates both the coulomb interaction and the hydrostatic pressure increase around the chain in a compromise which minimises the free energy and keeps water chemical potential constant throughout. Stretching strongly favors parallel cylinder nematic order in polyelectrolyte brushes on a surface or in the slit between two surfaces when the polyelectrolyte chains function as bridges. Strong, stiffly stretched chains result when the molarity of the fixed charge distribution is larger than the molarity of the neutral salt solution with which the brushes are in equilibrium. The relevance of these two systems to the endothelial cells which cover the walls of blood vessels is discussed. PMID- 1751774 TI - Tumor necrosis factor-alpha, interleukin 1, and phorbol myristate acetate are independent activators of NF-kappa B which differentially activate T cells. AB - Gene expression in eukaryotic cells can be altered in different ways by extracellular agents, including mitogens and cytokines. Such differential gene expression is mediated in part through the effects of these stimuli on distinct sets of cellular transcription factors. In this report, the effects of phorbol myristate acetate, tumor necrosis factor-alpha (TNF-alpha), and interleukin 1 (IL 1) on differential gene expression in the LBRM mouse T-lymphoma cell line are examined. Although these three different stimuli produce similar levels of induction of the NF-kappa B transcription factor, it is reported that they cause differential expression of other cellular activation genes, including c-fos and IL-2. The roles of IL-1 and TNF-alpha were also analyzed in EL-4 cells in the presence of a second activator, ionomycin. IL-1, but not TNF-alpha, was found to stimulate the IL-2 enhancer in the presence of this costimulator. These findings suggest that one transcription factor can be the target of cellular activators that exert otherwise different effects on gene expression. Cellular activation pathways can therefore be defined by the set of transcription factors stimulated within a cell. This approach may allow a more precise definition of the requirements for differential gene activation in different cell types and thereby provide a basis for the selective manipulation of gene expression in cytokine responsive cells. PMID- 1751775 TI - Constitutive and NF-kappa B-like proteins in the regulation of the serum amyloid A gene by interleukin 1. AB - Serum amyloid A (SAA) is a major acute-phase protein whose chronic production by the liver can lead to the fatal disorder of secondary amyloidosis. Control of SAA is mediated by several inflammatory cytokines, including interleukin 1 (IL-1). To study the cis-acting regulatory elements responsible for constitutive and IL-1 induced expression, DNA constructs containing varying lengths of the promoter region from the human SAA2 beta gene 5' to the bacterial reporter gene, chloramphenicol acetyltransferase (CAT), were generated and transfected into human hepatoma cells, HepG2. Both positive and negative regulatory elements were found in the 5' flanking region of the human SAA2 beta gene. The more proximal region contains an IL-1 enhancer sequence GGGACTTTCC (SAA kappa B1; between -82 and -91), the binding site for the ubiquitous transcription factor NF-kappa B. IL 1 induction of the binding of nuclear factor to this sequence is maximal between 5 min and 30 min after incubation with IL-1 and negative in cells incubated for 60 min or longer. Mutation of the SAA kappa B1 sequence to a nonbinding form of NF-kappa B (CTCACTTTCC) abolishes the IL-1 effect. The SAA 5' region also contained an upstream repressor element, shown by transfection experiments. Within this element, a second NF-kappa B binding site (SAA kappa B2; -626 to 635) was found, and mutation of SAA kappa B2 to a non-NF-kappa B-binding form results in an increase in both constitutive + IL-1 stimulated SAA transcription.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751776 TI - Temperature is a powerful promoter of interleukin 2 transcription. AB - Elevated temperature has profound effects on the immune system, particularly by increasing T-cell proliferation rates, interleukin 1 (IL-1)-driven secretion of IL-2, and primary antibody responses to T-dependent antigens. Therefore, this study shows, in detail, the effects of incubation temperature (29 degrees C to 41 degrees C) on proliferation, IL-2 secretion, and IL-2 mRNA expression in both a murine thymoma cell line (EL4-6.1) and in nontransformed murine splenocytes. Temperature was found to be a positive regulator of IL-2 secretion whether or not IL-1 was part of the activation signal. Parallel effects were observed at the level of IL-2 gene expression. Messenger RNA was quantitated with a novel system, using solution hybridization followed by detection of RNA-DNA complexes by enzyme immunoassay. The time to onset of IL-2 mRNA expression was inversely related to temperature, and mRNA levels increased 20- to 50-fold with increases in average incubation temperature from 29 degrees C to 39 degrees C. This effect was observed whether cells were incubated at constant temperature or exposed intermittently to elevated temperature. Over the same intervals of time and temperature, mRNA levels for tau-actin and beta-tubulin remained relatively constant. Taken together, these findings suggest that temperature-mediated augmentation of IL-2 secretion does not require the presence of IL-1, and that the effect occurs at a pretranslational level. PMID- 1751777 TI - Rapid acquisition of an enhanced capacity to produce tumor necrosis factor, alpha/beta interferon, and interleukin 6 after implantation of tumor cells. AB - This study shows that the ability of mice to produce tumor necrosis factor (TNF), alpha/beta interferon (IFN-alpha/beta), and interleukin 6 (IL-6), but not interleukin 1 (IL-1), in response to endotoxin was dramatically augmented within 24 h of intradermal implantation of 10(6) tumor cells. Tumor cell implantation also caused endotoxin-independent appearance of IFN-alpha/beta and IL-6 in serum within 24 h. Priming for endotoxin-induced TNF production was not evident during the first 12 h of tumor cell implantation and it had decreased by 72 h. However, this decrease was followed by a second peak of priming on day 6 of tumor growth. Priming for endotoxin-induced TNF production was not induced by injection of dead tumor cells, the products of live tumor cells, or syngeneic or allogeneic splenocytes. Priming for TNF production was associated with an increased susceptibility of mice to endotoxin toxicity. These data suggest the existence of a cytokine-dependent host defense mechanism that is rapidly elicited in response to tumor cell implantation. PMID- 1751778 TI - Antibodies to interleukin 3 as probes for the interaction of interleukin 3 with its receptor. AB - A series of antibodies, directed against murine interleukin-3 (IL-3) or synthetic peptides corresponding to portions of the IL-3 sequence, has been used to detect receptor-bound IL-3 on the surface of cells. An assay was developed in which the bound primary antibody was detected using a biotinylated secondary antibody and fluorescein isothiocyanate-labeled streptavidin, followed by analysis on a fluorescence-activated cell sorter. The fluorescence signal was shown to be specific for cells known to express IL-3 receptors and was dependent on the preincubation of cells with IL-3 under conditions that did not allow internalization of receptors. Antisera raised against full-length synthetic IL-3 or to the N-terminal 29 residues were found to give equivalent signals. On the other hand, antibodies to residues 91-118 showed no signal in this assay, despite being able to bind to IL-3 in solution and neutralize IL-3 bioactivity. When peptides corresponding to residues 30-43 and 123-140 were incubated with the anti IL-3 antiserum, the majority of the fluorescence signal was abolished, indicating that these two peptides contained the primary epitopes being recognized by the antiserum in this assay. This antiserum also bound to the 91-118 peptide, but the corresponding peptide was not able to reduce the fluorescence signal in a similar competition assay. These results suggest that the 91-118 region is not accessible to antibody when IL-3 is bound to its receptor, whereas at least portions of epitopes 1-29, 30-43, and 123-140 remain accessible to antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751779 TI - Differential activity of granulocyte-macrophage and macrophage colony stimulating factors on bone resorption in fetal rat long bone organ cultures. AB - In this study, the ability of recombinant human macrophage (M) and murine granulocyte-macrophage (GM) colony stimulating factor (CSF) to affect both basal and stimulated bone resorption in fetal rat long-bone organ cultures was assessed. It was found that M-CSF does not affect basal bone resorption or bone resorption stimulated by parathyroid hormone, recombinant human interleukin 1 beta, prostaglandin E2 (PGE2), and 1,25 dihydroxy vitamin D3. Specifically, M-CSF at concentrations as high as 30 nM (1 microgram/mL) did not modulate 45Ca release from fetal rat long bones stimulated by these agents. The addition of recombinant murine GM-CSF (at equal molar concentration to M-CSF) also did not affect bone resorption stimulated by parathyroid hormone and interleukin 1 beta. On the other hand, GM-CSF stimulated basal bone resorption over a 120-h period and augmented the resorption mediated by exogenous PGE2 over a 48-h incubation. In addition, GM CSF was shown to stimulate production of endogenous PGE2 in cultures of bone rudiments. These effects on bone resorption were blocked by the addition of prostaglandin synthesis inhibitors and specific antibodies to murine GM-CSF. These data indicate that M-CSF does not act as a regulator of bone turnover, but GM-CSF may cause bone resorption by stimulating the synthesis of PGE2 in bone. PMID- 1751780 TI - Regulation of the interleukin 2 receptor complex tyrosine kinase activity in vitro. AB - Interleukin 2 (IL-2) has been shown to stimulate tyrosine phosphorylation of a number of proteins requiring only the p75 beta chain of the IL-2 receptor. Unlike the receptors for epidermal growth factor, insulin, and other growth factors, the p55-alpha and p75-beta chains of the IL-2 receptor have no tyrosine protein kinase domain suggesting that the IL-2 receptor complex activates protein kinases by a unique mechanism. The activation of tyrosine kinases by IL-2 in situ was studied and using a novel methodology has shown tyrosine kinase activity associated with the purified IL-2R complex in vitro. IL-2 stimulated the in situ tyrosine phosphorylation of 97 kDa and 58 kDa proteins which bound to poly(Glu,Tyr)4:1, a substrate for tyrosine protein kinases, suggesting these proteins had characteristics found in almost all tyrosine kinases. IL-2 was found to stimulate tyrosine protein kinase activity in receptor extracts partially purified from human T lymphocytes and the YT cell line. Biotinylated IL-2 was used to precipitate the high-affinity-receptor complex and phosphoproteins associated with it. The data indicated that the 97-kDa and 58-kDa phosphotyrosyl proteins were tightly associated with the IL-2 receptor complex. These proteins were phosphorylated on tyrosine residues by IL-2 stimulation of intact cells and ligand treatment of in vitro receptor extracts. Furthermore, the 97-kDa and 58 kDa proteins were found in streptavidin-agarose/biotinylated IL-2 purified receptor preparations and showed high affinity for tyrosine kinase substrate support matrixes. The experiments suggest that these two proteins are potential candidates for tyrosine kinases involved in the IL-2R complex signal transduction process. PMID- 1751781 TI - Recombinant antibodies. AB - Many fundamental advances in our understanding of the structure and function of eukaryotic genes were derived from the study of antibody genes. Examples include mRNA splicing and rearrangement to generate antibody diversity. The capacity to immortalize an individual B cell using cell fusion permitted the generation of monoclonal antibodies. Monoclonal antibodies have had wide application in many fields of the life sciences and beyond. Recent advances permitting manipulation of antibody genes using recombinant DNA techniques offer many advantages over conventional somatic cell hybridization techniques. Rodent monoclonals can be "humanized" and antibody isotype readily changed. Grafting of the complementarity determining regions from rodent to human framework regions demonstrated the importance of these hypervariable portions of the immunoglobulin to the integrity of the antibody combining site. Recombinant monoclonal antibodies (rMAb) or fragments thereof have been successfully produced in both prokaryotic and eukaryotic hosts at levels equal to those produced by hybridomas. Successful efforts to express rMAbs in plants and other large capacity systems suggest that rMAbs can be produced inexpensively. Use of antibody catalysis and antibodies mimicking various receptors or ligands have numerous applications. Technology developed to immortalize the heavy and light chain repertoire permits the generation in vitro of recombinatorial libraries of antibodies. The capacity to artificially generate high-affinity antibodies in vitro using the methods of recombinant DNA technology has enormous pharmaceutical and industrial potential. PMID- 1751782 TI - Use of severe combined immunodeficient (SCID) mice to produce human hybridoma ascites. AB - The use of the severe combined immunodeficient mouse (SCID), CB-17/Icr//Imd-SCID, was investigated for the production of human hybridoma ascites containing human antibody. Human-human hybridomas, generated from the fusion of lymphocytes isolated from regional draining lymph nodes of cancer patients with the SHFP-1 fusion partner, were injected i.p. at various cell concentrations into pristane primed SCID mice. Ascites growth was typically observed at 7-14 days postinoculation. No significant differences in ascites yield or production were observed between IgG- and IgM-secreting hybridomas. Yields of immunoreactive human immunoglobulin ranged from approximately 0.5 to 3 mg/ml of harvested ascites. The ease and relatively low cost suggest that the use of SCID mice is preferred over conventional and costly large-scale industrial procedures. PMID- 1751783 TI - Human monoclonal antibody JDB1 reacts with cytoplasmic and membrane bound antigens present on a variety of human breast tumor cell lines. AB - The human monoclonal antibody JDB1 was examined for reactivity to five breast cancer cell lines as well as normal fibroblasts. The JDB1 clone secretes both IgG3 and IgM antibody. In these studies both the total antibody (containing IgG3 and IgM) as well as the purified IgG3 and IgM fractions were examined for tumor cell binding reactivity. Peroxidase staining was observed in the breast cancer lines SW527, MCF-7, T47D, SKBR3, and MDAMB231, while GM179 and GM5758 fibroblast lines were negative for antibody binding. Tumor cells were examined using two techniques: a drop cell technique in which cells were fixed onto slides and also a cover slip assay in which cells were grown onto sterile cover slips and subsequently stained with the human monoclonal antibody using a peroxidase technique. Both cytoplasmic and membrane staining were observed for all of the breast tumor cells tested using both assays. In addition, a cellular ELISA was developed and used to quantitate the binding of these antibodies to tumor cells. PMID- 1751784 TI - Antigens recognized by two human monoclonal IgM anticolon cancer antibodies, 16.88 and C-OU1 (B9165). AB - We have compared by SDS-PAGE Western blotting the molecules detected by two human monoclonal antibodies, C-OU1 and 16.88. The antibodies have previously been shown to detect a cytoplasmatic antigen with an Mr of 43 kD present in colon adenocarcinoma cell lines and in colon cancer tissues. We now demonstrate that these antibodies differ significantly in their fine specificity, resulting in a quite dissimilar tumor selectivity. The antibody 16.88, in addition to reactivity with the 43-kD molecule, also recognizes a 190-kD molecule present both in melanoma cells and in cells previously reported as 16.88 antigen positive. The 16.88 antibody does not detect a 43-kD molecule in extracts of melanoma cells. The 190-kD component was not detectable in hepatoma or mamma carcinoma cells, both of which showed presence of the 43-kD molecule. The C-OU1 antibody shows no reactivity with the 190-kD molecule in any of the cells tested or with other proteins in melanoma cells. Radiolabeled 16.88 antibody shows better localization to melanoma cancer than to colon cancer xenograft transplanted onto nude mice. These findings indicate the presence of a tumor-associated antigen not previously described and have obvious implications for potential clinical uses of the antibodies. PMID- 1751785 TI - Dietary protein restriction in chronic renal failure: nutritional efficacy, compliance, and progression of renal insufficiency. AB - Two findings prompted investigators to examine the effects of dietary manipulation on progression of chronic renal failure: dietary protein restriction is an effective method of ameliorating uremic symptoms and the course of renal insufficiency in an individual patient is predictable. Results from studies of patients and animals with chronic renal failure suggested that a low-protein, phosphorus-restricted diet could slow the rate of loss of renal function. In evaluating these studies, three questions should be considered. First, is the diet nutritionally adequate? Second, has dietary compliance been monitored and achieved? Third, is there evidence that restricting the diet will change the rate of loss of renal function? The scientific basis for each of these questions is addressed in this review. PMID- 1751786 TI - Is there a "point of no return" in progressive renal disease? AB - The pathogenesis of progressive renal damage is most probably multifactorial. Whatever the mechanisms involved in renal disease progression, the existence of a "point of no return" has been hypothesized, that is, a stage of structural and functional damage beyond which progression of renal disease occurs independently of dietary measures and/or pharmacological treatment. In experimental animals, dietary protein and phosphate restriction is not fully successful in ameliorating the progression of functional deterioration if administered when renal injury is severe and long standing. Similarly, late treatment with various pharmacological agents (mainly antihypertensive drugs) is less effective than early administration of the same substances. A serum creatinine of 176 mumol/L seems a critical point discriminating the results of either dietary protein and phosphate restriction or antihypertensive treatment in patients with chronic renal disease. The protective effects of both dietary and nondietary intervention seem to be most effective when at least 50% of the residual renal mass is still functioning. The extent to which glomerular sclerosis, vascular hyalinosis, and interstitial fibrosis have already developed can probably blunt or avert the expected results of treatment. Some clinical tests may identify those patients who would benefit from measures such as the reduction in glomerular hemodynamic stress, the long term inhibition of the renin-angiotensin system, and the aggressive treatment of systemic hypertension. The continuous search for a rational preventive treatment before the disease process has reached the "point of no return" will undoubtedly constitute a formidable task for the modern nephrologist. PMID- 1751787 TI - Adjunctive therapy with intravenous human immunoglobulin G improves survival of patients with acute renal failure. AB - The objective of this prospective, randomized, double-blind, placebo-controlled clinical trial was to evaluate the efficacy of adjunctive therapy with iv human immunoglobulin G in reducing the morbidity and mortality associated with acute renal failure. Forty patients greater than or equal to 18 yr of age who were identified within 48 h of the onset of acute renal failure and who met the enrollment criteria were enrolled in the study. Thirty-five patients were considered evaluable. Patients were grouped according to the admitting service (medical or surgical/trauma) and were randomized to receive either immunoglobulin G (400 mg/kg body wt) or placebo (normal saline; 8 mL/kg body wt) at study entry and then weekly thereafter for a maximum of 4 doses. The groups were well balanced with respect to demographics, clinical presentation, and severity of illness (APACHE II scores). A significant reduction in mortality at 42 days after study entry was observed. Two of 17 (12%) patients in the immunoglobulin G treated group compared with 8 of 18 (44%) patients in the placebo-treated group died (P = 0.025). No differences were observed in the frequency of major complications that occurred in association with acute renal failure. However, in patients who manifested infection, greater survival was observed in the immunoglobulin G treatment group. The results suggest that immunoglobulin G administered at the onset of acute renal failure reduced mortality possibly by decreasing the severity of infectious complications associated with the occurrence of of acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751788 TI - The influence of mannitol on myoglobinuric acute renal failure: functional, biochemical, and morphological assessments. AB - This study was undertaken to explore the protective influence of mannitol against the glycerol model of myohemoglobinuric acute renal failure. Three hypotheses were tested: (1) mannitol confers cytoprotection by acutely blunting renal hypoperfusion, thereby improving tubular cell energetics; (2) as an hydroxyl radical (OH.) scavenger, mannitol mitigates Fe-driven lipid peroxidation and, hence, decreases tubular cell necrosis; and (3) mannitol prevents intrarenal heme pigment trapping, decreasing cast formation. Rats were injected with 50% glycerol (10 mL/kg im), followed immediately by an iv mannitol (1.25 mL/100 g over 1 h) or sham infusion. Mannitol induced a brisk diuresis (approximately 5.7 mL/2 h; approximately 35 mg of heme protein excreted), whereas glycerol controls were anuric. Mannitol did not significantly increase postglycerol RBF (2.8 mL/min), and it paradoxically worsened cellular energetics, halving cortical ATP concentrations at 1 h. However, this adverse effect on ATP was transient, correlating with active diuresis. Glycerol did not induce convincing in vivo lipid peroxidation (malondialdehyde; conjugated diene assay), and mannitol did not block Fe-driven in vitro lipid peroxidation of isolated brush border membrane vesicles. Na benzoate, an OH. scavenger, conferred no in vivo or in vitro protection. However, Na2SO4, not an OH. scavenger, reproduced the diuretic and in vivo protective effects of mannitol. Purified myoglobin infusion (35 mg) largely negated the beneficial action of mannitol. It was concluded that mannitol confers functional but not cytoprotection against the glycerol acute renal failure model, it acutely worsens renal bioenergetics, and its protective influence is probably due to a diuretic, not an antioxidant, effect. PMID- 1751789 TI - Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease. AB - Thirty-seven young healthy subjects with normal renal function were studied to assess the quantitative effect of protein intake on creatinine clearance. A standard 24-h urine collection and blood sample at the end of the collection were obtained for creatinine and urea concentrations. Correlations between creatinine clearance and urinary urea nitrogen excretion (r = 0.8; P less than 0.0001) and calculated protein intake (r = 0.8; P less than 0.0001) were observed. A significant relationship between creatinine clearance and urea nitrogen excretion was also demonstrated in 28 elderly healthy subjects and 33 patients with renal disease. To demonstrate a cause and effect between urea nitrogen excretion and creatinine clearance in healthy subjects, 18 of the 37 healthy subjects repeated the 24-h urine collection and blood sample after ingesting 5 g of urea in addition to their usual diet. Mean urinary urea nitrogen excretion increased from a mean value of 9.8 +/- 4.0 to 11.8 +/- 4.0 g/day. There was a strong correlation between the changes in urea nitrogen excretion and the changes in creatinine clearance. In acute studies with oral protein loading, there was a significant correlation between creatinine clearance and urinary urea nitrogen excretion. It was concluded that protein intake has a direct and quantitative effect on creatinine clearance in healthy subjects. In normal humans, it is likely that GFR is not a fixed function. Thus, a low creatinine clearance is not a categorical sign of renal disease. A low creatinine clearance adjusted for urea nitrogen excretion may be a useful clinical tool to assess renal function. PMID- 1751790 TI - Factors affecting inorganic mercury transport and toxicity in the isolated perfused proximal tubule. AB - The effects of cysteine (80 microM), glutathione (80 microM), rabbit albumin (100 microM), and an ultrafiltrate of rabbit plasma on the toxicity and transport of inorganic mercury (Hg2+; 18.4 microM) in isolated perfused S1, S2, and S3 segments of the renal proximal tubule from the rabbit were studied. Cellular and tubular injuries were assessed qualitatively by light microscopy observations and quantitatively by the tubular leak of the volume marker 3H-glucose. The lumen-to bath transport of inorganic mercury was assessed by measuring both the rate of disappearance of inorganic mercury from the luminal fluid and the rate of appearance of inorganic mercury in the bath. When glutathione was added to the perfusate containing the inorganic mercury, no signs of epithelial cell necrosis or injury were detected in any of the three segments of the proximal tubule. There was also an absence of or a decrease in cellular injury in the epithelium of the same tubular segments when either cysteine or the ultrafiltrate was present in the perfusate. However, when rabbit albumin and inorganic mercury were present in the perfusate, severe degenerative and necrotic changes occurred very rapidly in the epithelium of all three segments of the proximal tubule. In almost every instance where glutathione, cysteine, or the plasma ultrafiltrate were present in the perfusate, the disappearance flux of inorganic mercury from the tubular lumen into the tubular epithelium was lowered. It was concluded that glutathione, cysteine, and the ultrafiltrate of rabbit plasma provide isolated perfused S1, S2, and S3 segments of the proximal tubule varying degrees of protection from the toxic effects of inorganic mercury. This protection appears to be related to a decrease in the movement of inorganic mercury across the luminal membrane of the tubular epithelial cells. PMID- 1751791 TI - Osmoregulatory betaine uptake by rat renal medullary slices. AB - Betaine is an osmolyte present in high concentrations in renal medullary cells. Betaine and other organic osmolytes, such as glycerophosphorylcholine, myo inositol, and sorbitol, have been shown to increase in concentration during antidiuresis when the inner medullary extracellular osmolality rises. Its concentration may increase in renal cells either by betaine uptake or by choline metabolism to betaine. These studies measured the uptake of (14C)betaine into cortical, outer medullary and inner medullary slices from rat kidney. The tissue to-medium ratio of (14C) betaine increased with increasing osmolality up to 450 mosmol/kg in outer medullary and inner medullary slices, but not in cortical slices. Betaine uptake increased when the osmolality was raised with NaCl or mannitol, but not with urea. When LiCl was substituted for NaCl in a medium of 300 mosmol/kg, there was significant inhibition of betaine uptake, although the tissue-to-medium ratios remained greater then unity. Thus, increases in osmolality stimulate betaine uptake in rat renal medullary slices and this uptake occurs by both sodium-dependent and sodium-independent betaine transport. PMID- 1751792 TI - Chloride and membrane potential dependence of sodium ion-proline symport. AB - Proline accumulation by renal proximal tubule brush border membrane vesicles is Na+ dependent, but little is known about the role of anions or membrane potential on proline uptake. Recent studies in a variety of transport systems, including rat renal brush border membrane vesicles, indicate that halide anions chloride (Cl-) and bromide (Br-) are essential for glycine, beta-alanine, gamma aminobutyric acid, and taurine uptake, so the possibility that Na(+)-proline symport is Cl- dependent was explored. Also, the role of membrane potential on transport was assessed by determining the effect of external anions with different membrane permeabilities. The ratio of initial rate Cl- stimulated to thiocyanate (SCN)(-)-stimulated uptake values serves to measure Cl- dependence. The initial rate of proline uptake to equilibrium value was 3.11 +/- 0.5 (SE) in the presence of Cl- versus SCN-. The ratio for D-glucose, whose uptake is governed only by electrogenic status of the membrane, was 0.61 +/- 0.47 (P less than 0.001 versus proline). In another series of experiments, uptake values for various anions as a percent of equilibrium (I/E x 100) were: SCN-, 84.9 +/- 10.9; NO3, 49.9 +/- 11.0; SO4(2-), 27.3 +/- 4.4; F-, 68.5 +/- 18.3; Cl-, 164.1 +/- 44.6; Br-, 150.6 +/- 30.2; I-, 56.7 +/- 13.5. The stoichiometry of uptake by Hill plot analysis of proline uptake in the presence of varying concentrations of Na+ (0 to 100 mM) and Cl- (0 to 100 mM) was 2Na+:1Cl-:1 proline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751793 TI - Intradialytic modulation of granulocyte C5a receptors. AB - Hemodialysis with new cellulosic membranes is associated with profound granulocytopenia, with a nadir 15 min after initiation, followed by a rebound leukocytosis seen 1 h after initiation and persisting up to the termination of dialysis. The rapid reversal of granulocytopenia during hemodialysis has previously been ascribed to down-regulation of granulocyte C5a receptors. In this report, a method of characterizing C5a receptors by using a novel probe consisting of C5a attached to biotin via a six-carbon spacer chain is described. Cellulose acetate electrophoresis and cation exchange HPLC demonstrated a biotin to-C5a ratio of 1:1. Analysis of granulocyte cell surface C5a receptors were performed with the probe with a fluorescein-avidin conjugate and by using fluorescence flow cytometry. The maximum decrease in C5a receptors was measured at the 15-min sampling time, when the number of C5a receptor decreased from 189,240 +/- 24,500 predialysis to 160,740 +/- 19,380 receptors (P was not significant) at the nadir of granulocytopenia. However, during recovery from neutropenia, granulocyte cell surface C5a receptors increased to 172,140 +/- 19,380 at 30 min and 193,800 +/- 24,510 at the end of dialysis. Concentrations of C3a and C5a peaked at 15 min and declined rapidly thereafter, but both remained significantly above baseline at all times. These studies suggest that down regulation of C5a receptors, which is seen maximally at 15 min after initiation of dialysis, does not sufficiently account for the reversal of granulocytopenia during hemodialysis. PMID- 1751794 TI - Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. AB - This study analyzed blood pressure in hemodialysis patients treated with epoetin beta in multicenter trials. Antihypertensive drugs were prescribed as usual. Placebo-controlled trials compared epoetin (100 to 150 U/kg; N = 151) with placebo (N = 78) for 82 days. Hemoglobin (108 +/- 18 versus 75 +/- 14 g/L) (mean +/- SD) and diastolic blood pressure (84 +/- 14 versus 78 +/- 15 mm Hg) were greater (P less than 0.05) after epoetin. Clinically important increases in blood pressure (increases in diastolic blood pressure greater than or equal to 10 mm Hg and/or drug therapy) were more frequent with epoetin (58 versus 37%; P = 0.005). A dose-response trial compared epoetin, 25 U/kg (N = 42), 100 U/kg (N = 40), and 200 U/kg (N = 39) for 138 days. Increases in hemoglobin were dose dependent, but clinically important increases in blood pressure were not. In analyses of all patients treated with epoetin (N = 272), no baseline or final level of hemoglobin, or rate of hemoglobin rise, was a threshold for a rise in blood pressure. Patients requiring antihypertensive drugs or having uncontrolled hypertension (diastolic blood pressure greater than 90 mm Hg) at baseline had decreases in blood pressure (P less than 0.05) with antihypertensive therapy. Thus, compared with placebo, 21% of patients had clinically important increases in blood pressure during amelioration of anemia. The baseline or final levels of hemoglobin, the extent or rate of hemoglobin rise, or uncontrolled hypertension or antihypertensive drug use at baseline were not confirmed as risks. Antihypertensive drug therapy was important for blood pressure control. PMID- 1751796 TI - Treatment of viral hepatitis. International Association for the Study of the Liver. Satellite meeting. Gold Coast, Australia, 3-5 September 1990. PMID- 1751795 TI - Improved method for the isolation of mouse glomeruli. PMID- 1751797 TI - Alpha-interferon combined with immunomodulation in the treatment of chronic hepatitis B. AB - Interferon has profound anti-viral, anti-proliferative and immunomodulatory effects. Future studies should be directed at observing how the immunomodulatory effects predict a response in certain groups of patients. Interferon is very useful in chronic hepatitis B but may require the addition of a steroid pulse. Individuals with low serum ALT appear to benefit most from a steroid pulse. Therapy should be given with a great deal of caution in patients with decompensated liver disease, as one may precipitate the untimely demise of the patient even though viral replication is decreased. One of the patients in the IFN study in fact did have decompensation after prednisone therapy, which subsequently led, a couple of months later, to a variceal haemorrhage. In summary, in treating hepatitis B viral infection, no single agent is totally effective and perhaps the combination of suppressing viral replication and augmenting the immune system is the optimal way to eradicate the virus. At present, an adequate response is found in only about 30-40% of patients even with 'optimal' therapy. PMID- 1751798 TI - Alpha-interferon therapy for chronic hepatitis B virus infection in children and Oriental patients. AB - In summary, these four studies showed that alpha-IFN therapy alone produced sustained inhibition of HBV replication in a minority of Chinese adults with chronic HBV infection. The response was not improved by instituting treatment at an earlier age. The major reason for the poor response in Chinese patients is probably immune tolerance as a result of early exposure to HBV. The response in Chinese patients with elevated pre-treatment serum ALT levels, who presumably had ongoing endogenous immune lysis of infected hepatocytes, was significantly better than and comparable with that reported in Caucasian patients. Prednisone priming did not provide any additional advantage over therapy with IFN alone in patients with normal pre-treatment serum ALT levels, but appeared to have additional benefit in patients with elevated ALT levels. PMID- 1751799 TI - Design of new anti-viral agents for chronic hepatitis B virus infection. AB - The effectiveness of therapies for chronic hepatitis B will depend on their ability to inhibit all HBV replicative intermediates including viral SC DNA as well as stimulating the host's immune system to clear virus and produce sustained immunity. Future therapies will require the use of combined treatments in 'cocktail-type arrangements' as outlined in this paper, linked with careful staging of the hepatitis B carrier state. PMID- 1751800 TI - Management of hepatitis D virus infection. PMID- 1751801 TI - Treatment of chronic hepatitis C with alpha-interferon. PMID- 1751802 TI - Alpha-interferon treatment of chronic hepatitis B infection: predictors of responsiveness. PMID- 1751803 TI - Dedifferentiation phenomena after denervation of mammalian adult vestibular receptors. AB - The effect of transecting the vestibular nerve on the vestibular sensory epithelium was studied in adult guinea-pigs. When denervation was complete, after fifteen days, the vestibular hair cells began to show morphological features of immaturity. After two months, the majority of hair cells showed a supporting cell phenotype. By four months, both hair cells and supporting cells had become morphologically similar to the epithelial cells which line the vestibular cavities. When denervation was incomplete, hair cells and supporting cells retained their normal phenotype. This, plus the dedifferentiation after complete denervation, indicates that the phenotypes of the hair cells and supporting cells are innervation-dependent. PMID- 1751804 TI - Embryonic mouse spinal cord motor neuron hybrid cells. AB - Studies of motor neurons are difficult because of limitations in their isolation and culture. One solution is to produce clonal neural hybrid cells that can express motor neuron characteristics; we fused an aminopterin-sensitive and neomycin-resistant mouse neuroblastoma cell line to isolated embryonic mouse spinal cord motor neurons. Several hybrid neuron cell lines expressing high levels of choline acetyltransferase (CHAT) enzyme activity were found. These were cloned and clones with high CHAT activity isolated. The hybrid nature of cloned cells was confirmed by karyotyping and determining glucose phosphate isomerase allozymes. The availability of these embryonic clonal hybrid cells will enable molecular, physiological, and biochemical studies to define motor neuron-specific properties. PMID- 1751805 TI - Back-firing of ventromedial medulla neurons from the spinal cord in awake, freely moving rats. AB - In the awake, freely moving rat we showed, by means of single-unit recordings and antidromic spinal cord activation, that at the ventromedial medulla level, in these particular experimental conditions, the 'multimodal, multireceptive' units excited by auditory, cutaneous non-noxious and noxious stimuli are possibly involved in a spinal descending control system. These neurons were back-fired from the medial part of the lateral funiculus, hence they probably projected to the dorsal and intermediate horn of the cord, and not to the ventral horn, which emphasizes a role in the control of nociception. Due to their convergent properties, these units are probably involved in nonspecific aspects of nociception such as alertness or stress. PMID- 1751806 TI - Nuclear membrane antigen specific to nerve and muscle tissues. AB - A monoclonal antibody, 2F7, raised against a nuclear protein subfraction recognized the nuclear membrane of nervous and muscular tissues of guinea pig, rat and rabbit, but no other tissue was stained. In the nervous system, both neurons and glial cells were labelled. An electron microscopic immunohistochemical study demonstrated that 2F7 antibody labelled the inner surface of the nuclear membrane. Western blot analysis on the nuclear envelope fraction containing nuclear lamina revealed that this antibody reacted to two minor component proteins of 80 and 82KDa. These 2F7 antigens expressed preferentially in the nervous and muscular tissues were distinct from the major nuclear envelope proteins reported so far and might be related to neuronal or muscular tissue-specific functions. PMID- 1751807 TI - Hepatocytes enhance neurite regeneration and survival from transected nerve terminals. AB - The culture of hepatocytes dissociated from adult mice by the collagenase perfusion method enables neurons or neuronal tissues to be cultured with hepatocytes or in hepatocyte-conditioned media. Co-culture with hepatocytes or hepatocyte-conditioned media enhances neurite regeneration and their survival from nerve-transected terminals of dorsal root ganglia with nerve fibers dissected from adult and aged mice. Hepatocytes secrete a factor which enhances not only neurite regeneration but also neurite survival. Activities of other known neurotrophic factors were not as crucial as those of the hepatocyte conditioned medium, suggesting that this factor may differ from other trophic ones. PMID- 1751808 TI - Intraretinal grafting restores visual function in light-blinded rats. AB - In seeing rats light flashes inhibit acoustic startle reflexes at short lead times. In contrast, visually impaired (light-blinded) rats show an early phase of exaggerated reflex expression, revealing the presence of pathological visual processing, and then an aberrant late phase of delayed inhibition. Grafting fetal retinal cells into the damaged retina entirely removed reflex facilitation and restored a modest degree of properly timed and statistically significant reflex inhibition. This restoration of visually-mediated behaviour, observed in two independent groups, reveals that intraretinal grafts provide useful information to blinded hosts. PMID- 1751809 TI - Nerve fibres in the uterine artery increase in number in pregnant guinea-pigs. AB - Perivascular nerves of the uterine artery were studied in four-month-old pregnant and non-pregnant guinea-pigs. In pregnancy, the uterine artery hypertrophies (more than two-fold growth in diameter and length and 50% increase in wall thickness), but its density of innervation remains high, because of the growth of many new axons. The axons in a complete transverse section of the vessel increase by 40%. The nerve bundles grow by 100%. Small nerve bundles increase more than large bundles: nearly 70% of the nerve bundles contain 10 or fewer axons in pregnant guinea-pigs (37% in non-pregnant animals). The increase in axon number is accompanied by formation of new varicosities, hence presumably of new neuromuscular junctions. PMID- 1751810 TI - Vitamin E supplements fail to protect mice from acute MPTP neurotoxicity. AB - The effect of chronic treatment with vitamin E (VE) on acute 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, as assessed by striatal dopamine (DA) depletion, was studied. Male C57B1/6J mice were fed VE (48 mg kg-1 per day, intragastric) for 4, 8, or 12 weeks prior to administration of MPTP (20 mg kg-1, i.p. x 3, 2 h intervals) or its diluent. Brain VE concentration was increased by exogenous supplements for 12 weeks. Striatal DA content was reduced by 85% to 90% after MPTP in control and VE-treated mice. Mice with elevated cerebral VE were not protected from MPTP toxicity, with DA content as an indicator. In conclusion, these findings indicate that moderate elevation of brain VE is not adequate for protecting DA-containing neurons against the toxic actions of a high dose of MPTP. PMID- 1751811 TI - Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. AB - Preliminary data suggest that rifaximin a new non-absorbable rifamycin-derivate, has beneficial effects on chronic portal systemic encephalopathy (PSE). To compare the efficacy and safety of rifaximin vs neomycin in the treatment of the hyperammoniemic state of PSE, 30 cirrhotic patients with grade I to III of PSE were randomly allocated to one of two groups: group A (15 patients) receiving rifaximin (400 mg/8h) and group B (15 patients) neomycin (1gr/8h). The duration of treatment was 21 consecutive days. Age, sex, hepatic and renal function, level of PSE, EEG and number connection test were similar in both groups. A significant decrease in blood ammonia levels was observed at the end of the treatment period in both groups; moreover rifaximin produced an earlier reduction of blood ammonia levels. The neuropsychic syndrome related to the PSE improved in both groups without significant difference. No side effects attributable to therapy were observed in the rifaximin group. These results indicate that, rifaximin is at least as effective as neomycin in the achievement and maintenance of low blood ammonia levels in cirrhotics with chronic PSE. PMID- 1751812 TI - Insufficiency of local approach regarding treatment of early gastric cancer. AB - Out of 1041 patients who underwent surgery for gastric cancer between 1968 and 1987, 120 patients suffered from early gastric cancer (11.5%). Until 1976, early gastric cancer was treated along the lines of surgical treatment of benign ulcer disease, i.e. by partial 2/3-gastric resection without lymphadenectomy, even though malignancy had been confirmed preoperatively in all cases. Since 1979 oncological criterias (subtotal or total gastrectomy with lymphadenectomy) have gained importance in treating early gastric carcinoma. In the case of mucosal carcinoma, the extent of surgical intervention does not have any influence on the 10-year survival rate. In treating submucosal carcinoma 10-year survival rates of 72.9 (+/- 7.2%) can only be achieved by performing total gastrectomy and lymphadenectomy whereas the 10-year survival rate after performing partial 2/3 gastric resection alone (p = 0.01) is only 17.6 (+/- 9.2%). Since mucosal and submucosal carcinoma cannot accurately be differentiated preoperatively, surgical intervention must be carried out in an oncological sense. The fact that 2/3 partial gastric resection does not generally ensure adequate therapy implies that local procedures are even less sufficient. Even in cases of mucosal infiltration only, local procedures such as laser therapy and local excision of the tumour cannot be considered being a curative approach, since hereby the probability of lymph node metastases (4%) is not taken into account. PMID- 1751813 TI - Pepsinogen A/pepsinogen C or pepsinogen A multiplied by gastrin in the diagnosis of gastric cancer? AB - Being pepsinogen A (PGA) levels generally reduced and pepsinogen C (PGC) increased in gastric cancer patients, PGA/PGC ratio has been proposed as a useful marker of the tumour. We tested PGA, PGC and Gastrin (G) levels in patients with gastric cancer (39) and, as a control, in patients with epithelial dysplasia (21), chronic atrophic gastritis (57), gastric ulcer (11) or subjects lacking major or minor endoscopic and microscopic changes at gastroscopy (48). PGA and PGA/PGC levels were significantly reduced in gastric cancer patients (p less than 0.005 and p less than 0.0001 respectively with analysis of variance). Gastrin levels were also reduced in the same patients (p less than 0.005). We therefore adopted an index number (PGA x Gastrin) which was also dramatically reduced in gastric cancer (p less than 0.005); using an arbitrarily chosen cut-off, the "marker" showed very high sensitivity (76%), specificity (96%) and overall accuracy (74%, by Youden J test). We therefore suggest the use of the index number PGA x G in the diagnosis of gastric cancer, as the most useful gastrin presently available, to our knowledge. PMID- 1751814 TI - A nine year retrospective analysis of resectable pancreatic cancer at the National Cancer Center Hospital in Tokyo: clues to diagnosis and diagnostic assessment. AB - A nine year retrospective survey was carried out at the National Cancer Center Hospital in order to define the diagnostic clues and most suitable diagnostic assessment in resectable pancreatic cancer patients. Forty six cases were detected (27 pancreatic head cancers, 19 pancreatic body and tail cancers). There were 8, 26, 3 and 9 cases of t1, t2, t3 and t4 tumour size cancers, respectively. Abdominal pain and/or discomfort and back pain were the most common initial symptoms and chief complaints. Jaundice was present only in pancreatic head cancer cases. Abnormal GTT and CA 19-9 were the biochemical tests most commonly found abnormal, irrespective of tumour size. ERCP followed by US and CT were the most accurate technical tests. The best care toward the awareness of the initial symptoms needs to be followed, as a first choice, by a proper biochemical (CA 19 9, GTT) and technical (US, ERCP, CT) assessment in the hope of identifying those patients whose prognosis might be improved by an early operation. PMID- 1751815 TI - Modifications of the trophism of intestinal mucosa after intestinal and bilio pancreatic diversion in the rat. AB - Morphofunctional alterations to the intestinal mucosa are influenced by three main factors: food, bilio-pancreatic secretions, intestinal hormones. In order to assess the importance of each one, histological and histochemical tests were performed on different segments of intestine taken from rats which were sacrificed one month after the following procedure: gastrojejunal anastomosis on a Roux loop (Model I); same procedure plus biliopancreatic bypass into the jejunum (Model II). When compared to the controls, Model I duodenum samples revealed hypertrophy of the entire wall with "bundles" of villi, while Model II samples showed a clear hypotrophy and reduction in the number of duodenal villi. To such modifications of the duodenum correspond longer, thinner villi in the other bowel segments, particularly in the jejunum and distal ileum. These results suggest that the predominant trophic effect derives from contact with biliopancreatic secretions at a proximal level. The modifications of the duodenal mucosa appear to regulate the trophism of the distal segments probably by the secretion of distant acting enterohormones. PMID- 1751816 TI - Ultrasonographic study of the Wirsung duct caliber after meal. AB - The pancreatic duct or at least parts of this structure can be demonstrated today by sonography in 50-82% according to various authors. We have measured the caliber of the sonographically visualized pancreatic duct in 20 normal subjects after physiological stimulation with meal. The mean caliber of the duct markedly increased after meal. During dilatation a longer segment of duct is more clearly visualized. It is possible to document an increase of caliber of Wirsung duct "in vivo" as an evident sign of pancreatic secretion. PMID- 1751817 TI - Stroke-cirrhosis relationship: an autopsy study in a heavy drinking population. AB - A positive association between alcohol consumption and stroke incidence has been clearly established. The present study evaluated the frequency of stroke in a sample of 500 autopsied patients affected by liver cirrhosis mainly due to chronic alcohol abuse as confirmed by the histologic pattern mostly of mixed and micronodular types. Frequency of stroke was compared to that of 4,741 non cirrhotic patients autopsied in the same period. Our findings demonstrate that stroke frequency, especially when due to thromboembolism, decreased significantly in cirrhotics. Therefore, hepatopathy is a crucial event in alcoholic patients. Nevertheless the concomitant presence of liver cirrhosis, in studies dealing with this subject, is not being currently evaluated. PMID- 1751818 TI - Prevalence of Helicobacter pylori in military barracks. PMID- 1751819 TI - Cirrhosis associated with homozygous alpha-1 antitrypsin deficiency in the adult: a case report. AB - A 34 year old woman admitted to the department of Gastroenterology of Florence hospital was diagnosed as suffering from liver cirrhosis with an alpha-1 antitrypsin deficiency (PiZZ phenotype). Liver biopsy showed the presence of intra-hepatocyte PAS-positive inclusions and the presence of alpha-1 antitrypsin was confirmed using the immunoperoxidase technique. No other organ appeared to be affected and respiratory function tests were within normal limits. The quantitative assay of alpha-1 antitrypsin was higher than values reported in the literature for PiZZ homozygotes. The authors report the case and discuss some aspects of this disease. PMID- 1751820 TI - A case of portal thrombosis arisen after treatment with dihydroergotamine. AB - We describe the case of a 42 year old woman with abdominal pain, ascites, and splenomegaly after having taken dihydroergotamine continuously for three months due to frequent hemicranic episodes. The celiac-mesenteric angiography demonstrated diffuse thrombosis of splenic, superior mesenteric and portal veins. No surgical intervention was possible. We believe that it is possible that dihydroerogotamine, a hydrogenated derivative of ergotamine, inasmuch as it is capable of causing peripheral vasoconstriction, intimal lesions, arterial and venous thrombi, was also the cause of our patient's portal thrombosis. We therefore suggest the minimum effective amount of the drug be utilized to achieve the relief of cephalalgia. PMID- 1751821 TI - Prognosis in primary biliary cirrhosis. A review. AB - Recent progress has been made in estimating prognosis in primary biliary cirrhosis using Cox models. These models have also demonstrated the therapeutic value of liver transplantation by comparing the observed survival for a group after transplantation with the expected survival without transplantation calculated from the Cox prognostic model. However, good risk patients and those not transplanted principally for hepatocellular failure may not have a survival advantage for many years. Cox models have several limitations: the selection criteria for the patient populations used to derive the models, the selection of the time at which the patients are evaluated, the poor prognostic accuracy for individual patients rather than patient groups and lastly the fact that they use variables derived at only one time point-time independent Cox models. Thus new statistical tools must be used to improve prediction of survival in individual patients with PBC in order to optimize timing of liver transplantation. In addition a more precise definition of the natural history of both symptomatic and asymptomatic forms of this disease is needed to evaluate the efficacy of therapeutic agents in randomized clinical trials. However, although use and timing of therapeutic intervention, including liver transplantation, still requires good clinical experience and judgement, statistical modelling does give some objective measurement of prognosis, which is useful for the clinician treating patients with PBC. At the same time that new treatments are being evaluated, there is an obvious need to improve prognostic tools for application to individual patients with PBC. This may be achieved by using serial data in a different form of modelling-time dependent Cox models. PMID- 1751822 TI - Ambulatory 24-hour oesophageal pH monitoring in normal subjects: a multicentre study in Italy. G.I.S.M.A.D. GOR Study Group. AB - A multicentre study was performed in Italy in order to establish normal values for acid gastro-oesophageal reflux. In 73 healthy subjects 24-hour oesophageal pH measurements were carried out under standardized conditions. The hourly number of reflux episodes and oesophageal acid exposure was assessed and analyzed by means of a computerized system. The distribution frequency of both parameters was skewed to the left, thus exhibiting a non-normal pattern. Acid reflux was lowest during the night and highest after meals. The oesophageal acid exposure and the number of reflux episodes were correlated both over 24 hours and in the subsets studied. A good agreement was found with data from previous reports. Our findings should be helpful in establishing a data base for physiological gastro oesophageal reflux. PMID- 1751823 TI - Sulphydryl mediation in the protection of gastric mucosal cells in tissue culture by acetaminophen. AB - Acetaminophen protects gastric mucosa in vivo against acute drug-induced damage and has also been shown to protect gastric epithelial cells in vitro. Protection afforded by acetaminophen in vitro is not associated with increased prostaglandin output. The present study evaluated whether protection of gastric epithelial cells by acetaminophen in vitro may be mediated by endogenous sulphydryls. Monolayers from a well-differentiated human gastric epithelial cell line were studied. Sodium taurocholate was used as a damaging agent and cell damage was assessed by the 51Cr release assay. Acetaminophen dose-dependently protected gastric cell monolayers against damage induced by sodium taurocholate. The sulphydryl blocker iodoacetamide dose-dependently decreased the concentration of nonprotein glutathione and cysteine and counteracted the protection afforded by acetaminophen. This suggests that sulphydryl compounds may mediate the protection of gastric epithelial cells by acetaminophen in vitro. PMID- 1751824 TI - Measuring gastric PGE2 release in healthy and alcoholic subjects after ethanol stimulation. AB - The aim of this work was to study the effect of 20% and 40% ethanol, administered acutely, on gastric PGE2 release in normal subjects and alcoholics. Ethanol 20% did not modify the release of PGE2 into the gastric juice, whereas 40% ethanol increased PGE2 release only in healthy subjects. The basal PGE2 levels were higher in alcoholic patients. PMID- 1751825 TI - Animal models of hepatocellular carcinoma: hepadnavirus-induced liver cancer in woodchucks. AB - Woodchuck hepatitis virus (WHV), a member of the Hepadnaviridae, is closely related to hepatitis-B virus (HBV) in its virus structure, genetic organization, and mechanism of replication. As with HBV in man, persistent WHV infection is common in natural woodchuck populations and is associated with chronic hepatitis and hepatocellular carcinoma (HCC). Experimental studies have established that WHV causes HCC in woodchucks. Chronic WHV carriage as an outcome of experimental infection is a function of animal age at time of exposure, virus dose, and, possibly, virus strain. Almost all (97%) chronic carriers developed histologically confirmed HCC within 3 years while no HCC developed in uninfected animals held concurrently in the same laboratory setting. The model has application in the study of underlying mechanisms of hepadnavirus-induced hepatocarcinogenesis and to the development of prophylactic and therapeutic strategies of disease control. PMID- 1751826 TI - Endoscopy: simply a technical tool or an integral part of clinical diagnosis? PMID- 1751827 TI - Mirizzi's syndrome: a contraindication to coelioscopic cholecystectomy. AB - An impacted gallstone in the cystic duct with subsequent inflammation and edema resulting in extrinsic compression of the common bile or common hepatic duct with obstructive jaundice is known as Mirizzi's syndrome. An uncommon complication of cholelithiasis, Mirizzi's syndrome should be included in the differential diagnosis of any patient who has extrahepatic biliary obstruction. We present a case of a patient who underwent open rather than coelioscopic cholecystectomy based upon the preoperative diagnosis of Mirizzi's syndrome. A multidisciplinary approach to such patients facilitates the decision between open and endoscopic cholecystectomy. Mirizzi's syndrome may represent a contraindication to endoscopic cholecystectomy. PMID- 1751828 TI - [Focus on stromelysine-3]. PMID- 1751829 TI - [Analytical limits in clinical pharmacokinetics: example of vinca-alkaloids]. AB - The radioimmunoassays commonly used to quantify plasmatic levels of vinca alkaloids (VA) have a specificity primarily directed towards the catharantine moiety of the molecules. They do not authorize a specific quantitation of parent drug with regard to the degradation or metabolism products issuing from vindoline substitutions especially those at positions 2, 3 or 4. However, they do allow quantitation of levels as low as 0.05 ng/ml from a 100-microliters sample volume. On the other hand, the HPLC methods which permit the separation of the deacetylated metabolites DVLB and DNVB cannot be used below 1 or 0.5 ng/ml of VA and require a 1-ml sample volume. These HPLC assays whose sensitivity is limited are less suitable for clinical VA pharmacokinetics than RIA but are essential for investigation of metabolism of these drugs both in animals, cellular and subcellular models. The quantitation of circulating VA levels during the apparent terminal elimination phase, which is essential for calculating the elimination half-life and clearance is still not fully accurate. This is because at these low levels estimated largely by RIA, cross-reactivity with a metabolite cannot be excluded. PMID- 1751830 TI - [Gangliosides and cancer]. AB - Gangliosides are glycosphingolipids which contain neuraminic acid. Although they are present in the plasma membranes of all cells, gangliosides are expressed differently, both quantitatively and qualitatively, in certain types of cancer. Modifications in ganglioside composition may account for some of the abnormal interactions between these tumor cells and their environment. Furthermore, some of the gangliosides are shed by tumor cells and may modify host immunity, thus contributing to the development of tumors. In cases of melanoma and neuroblastoma, the modifications in ganglioside expression are such that gangliosides may be used both as tumor markers and as targets for immunotherapy. PMID- 1751831 TI - [Prolymphocytic leukemia]. AB - Prolymphocytic leukemia is an entity characterized by morphologic, immunologic, clinical and behavioral features which allows its keeping apart from chronic lymphoid leukemia. Careful analysis of blood smear is the main step for its diagnosis. Our purpose is to remind this particular chronic lymphoproliferative syndrome which requires energetic initial treatment. Prolymphocytic leukemia de novo as well as a possible transformation of chronic lymphoid leukemia to prolymphocytic leukemia are discussed. PMID- 1751832 TI - [Suramin inhibits the proliferation and stimulates the differentiation of tumoral cell lines HT29-D4 and C6]. AB - Suramin is an anti-helminthic drug that has been shown to antagonize the effects of a variety of growth factors including EGF, PDGF and TGF beta. When added to the culture medium, suramin inhibited the proliferation of both human colonic adenocarcinoma cells HT29-D4 and rat glioma cells C6. Suramin also induced the differentiation of both cell lines: appearance of cellular extensions for C6 cells, enterocyte-like epithelial differentiation for HT29-D4-cells. In the latter case, suramin probably acts at the level of glucose metabolism, which is likely to be modulated by autocrine growth factors. The permanent secretion of such factors probably stimulates HT29-D4 proliferation and simultaneously inhibits their differentiation. It is hypothesized that interfering with this autocrine loop, suramin allows HT29-D4 cells to differentiate. PMID- 1751833 TI - [Prognosis of operable breast cancers in women aged under forty years]. AB - The present study is based on the data of a homogeneous series of 736 women with stage I and II operable breast cancer. The same methodology was used for treatment and follow-up. Eighty-seven patients were under 40 and 649 between 40 and 70 years ols. No statistical difference was noted between the distribution in these 2 groups regarding tumor size, the axillary or internal mammary nodal status or hormonal receptor levels. Small tumors were noted more frequently in the under 40 yr group. Overall survival was the same in both groups, independently of tumor size, axillary nodal status or hormonal receptors. Disease free survival differed between the 2 groups: local relapse risk was 1.6 times higher for women under 40 yr, in relation to a higher frequency of conservative treatment in this group. No difference was noted for DFS in relation a tumor size, axillary nodal status of hormonal receptors. PMID- 1751834 TI - [Chemotherapy with cisplatin and 5-fluorouracil in inoperable brain metastases of bronchopulmonary cancers]. AB - Chemotherapy is not a common treatment for cerebral metastases. The authors report results of combination chemotherapy with cisplatin (CDDP) and fluorouracil (5-FU). Sixteen men (age range 31-73 years) with brain metastases were treated with CDDP 20 mg/m2/day in continuous infusion for 5 days (d 1-5) and 5-FU 1 g/m2/day in continuous infusion for 4 days (d 1-4), and the treatment schedule repeated every 3 weeks. A brain computerized tomography after 2, 4 and 6 cycles was performed to assess efficacy. It was considered that complete response was achieved if no lesion was found on the CT scan, and partial response if at least half of the total volume had decreased. After 2 cycles, the response rate was therefore 8/16 (50%). Treatment toxicity was very mild with only 1 case of severe but reversible myelotoxicity (grade III). It is concluded that chemotherapy combination with CDDP and 5-FU is a useful treatment for brain metastasis of lung carcinoma. PMID- 1751835 TI - [Cisplatin, adriamycin and mitomycin-C in advanced stomach cancer]. AB - Eighteen patients with advanced gastric cancer were treated with cisplatin 80 mg/m2 d 1, doxorubicin 30 mg/m2 d 3 and mitomycin-C 12 mg/m2 d 3. One complete and 6 partial responses were observed in 17 evaluable patients (41%, confidence interval 17-65%). Median duration of response was 7 months; median survival was 8 months. One death due to toxicity was observed. This combination of 3 active drugs should not be recommended in cases of gastric cancers. PMID- 1751836 TI - [Untested treatments in "Cancer ward" by A. Solzhenitsin]. PMID- 1751837 TI - Measurement of interleukin 1 alpha and 1 beta (IL-1 alpha and IL-1 beta) in human cystic lesions of the jaw. Implications for the pathogenesis of radicular cysts. AB - Human radicular cystic tissue of jaws was found to contain between 0.823 pg/mg to 18.026 pg/mg interleukin 1 beta and from 0.34 pg/mg to 0.708 pg/mg interleukin 1 alpha. No IL-1 beta and alpha could be found in specimens from healthy patients. A finding which may be extremely relevant in cystic growth and episodes of alveolar bone resorption around the cystic lesion. PMID- 1751838 TI - Analysis of pH variation of various calcium hydroxide compounds in vitro. AB - Among the reasons for the use of calcium hydroxide products, there is their alkalinity. Variations in the alkalinity of six commonly used calcium hydroxide compounds were studied in vitro at different time intervals. All these compounds rendered the saline solution strongly alkaline. Dycal, Life, Nucap and Reocap, had a weaker effect as compared with Contrasil and to Pulpdent paste. Such differences in the pH values were accompanied by differences in calcium loss, as revealed by scanning electron microscopy. Differences in the alkaline pH values and calcium losses among these calcium hydroxide compounds may account for their different clinical effectiveness in vivo. PMID- 1751839 TI - Lectin histochemistry in the developing oto-maxillo-facial primordia of the mouse embryo. AB - The binding sites of several lectins (Con-A, SBA, WGA, PNA, RCA-I, UEA-I, DBA) were studied in the different tissues involved in mouse visceral cephalogenesis. As compared to various other lectins which have only a weak affinity for precartilaginous rudiments, PNA preceded by neuraminidase treatment shows a very strong fixation in the precartilaginous blastemata and their immediate environment. PNA receptors exist also on the enamel epithelium and mesenchymal sac. RCA affinity for blood vessels has also enabled detailed observations on the vascularization of the palatal shelves, particularly in area 3. Various other localizations have been described and correlated with other histochemical data. PMID- 1751840 TI - [The relations of the mandibular canal with the outer surfaces of the body of the mandible and the risks which arise from its injury]. AB - The investigations of relations and position of the mandibular canal (CM) were carried out on 80 mandibles (33 dentulous, 27 partly edentulous and 20 completely edentulous). The studies of relations of CM to the sides of mandibular body were accomplished by morphometric analysis of CM on consecutive transversal sections of mandibular body (54 preparations). The relation of the CM to be buccal or to the lingual side is expressed as the distance from the surface of the correspondent side of the mandibular body, which is shown in Table 1. According to these data, the position of the canal is at first proximate to the lingual side, and from the first molar tooth (M1) it approaches the buccal surface of the mandibular body. The position of the entire CM was determined by analysis of mandibular preparations (26) after removing the buccal osseous lamina. These investigations revealed that the position of the CM is predominantly buccal. Reconstruction of relations of the CM to the sides of mandibular body, according to the data obtained from transversal sections, and the real position of the CM are presented in Scheme I. The difference in direction lines of relations and of predominant position of the CM is a consequence of morphological characteristics of mandibular body. PMID- 1751841 TI - Crystal growth on enamel in relation to acid etching. AB - Crystal formation may occur during etching of enamel surfaces with phosphoric acid. In this in vitro study we observed, from a morphological standpoint, some crystals left after etching, on the surfaces, using the scanning electron microscope. More often, after water-spraying, a thin generalized precipitate remains on the surface. This precipitate may be harmful for the retention of composite resins. On few specimens we obtained needle-shaped or petal-like crystals. Crystal deposits were spread evenly, on the surface, or nucleated from different points. We tempted to identify these crystal formations by X-ray diffraction and microprobe analysis. Chemical identification seems very important because calcium phosphates solubility varies. Crystal dissolution in saliva can lead to marginal leakage and impairs the quality of esthetic restorations. On the contrary insoluble crystals may ensure microscopic retentions and crystal growth is now considered as an alternative for enamel pretreatment in bracket bonding. Crystal formation, in these first experiments, is too scarce to be used for crystal bonding. But it appears that two factors may enhance the crystal number: a preliminary topical application of fluoride and adsorption of an acidic protein, on the surface, before etching. However, further investigations are still necessary. PMID- 1751842 TI - Meta-analysis in aid of alcohol studies. PMID- 1751843 TI - Tobacco and the European common agricultural policy. AB - The common agricultural policy of the European Community subsidizes tobacco production to the tune of 1,300 million ecu a year (US$ 1,500 million, UK pounds 900 million). This amounts to 2,500 ecu ($3,100, pounds 1,700) per minute, and is more in one year than the total amount spent on tobacco subsidies by the US in the last 50 years. The purpose of this policy was to maintain farmers' incomes and adapt community production to demand. Demand for the dark tobaccos which dominate EC production has fallen, while demand for light flue cured tobacco like Virginia has risen. A complex system of production subsidies and quotas was intended to discourage production of the dark tobaccos, for which there is virtually no market, and lead to more Virginia production. The policy has failed. Expenditure has spiralled out of control, production of unmarketable tobacco varieties has risen enormously, and the EC is the world's largest importer of raw tobacco. As a result tobacco is being bought by the community for intervention storage and surpluses of the dark high tar varieties are being 'exported' to eastern Europe and north Africa at giveaway prices. There has been no effective monitoring or control of this policy. This paper explains how this has happened and argues that, in view of the health risks attached to tobacco, these subsidies should be abolished. PMID- 1751844 TI - An integrated approach to meta-analysis in alcohol studies. AB - The research design and methods utilized by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sizes, and random effects models. PMID- 1751845 TI - Coherence of the dependence syndrome in cocaine users. AB - The method of diagnosing drug dependence introduced in DSM-III-R is largely untested for drugs other than alcohol. Cocaine, unlike alcohol, lacks clearly identifiable withdrawal symptoms, yet is also considered highly addictive. Can criteria derived from the dependence syndrome concept be generally applied to treatment seeking cocaine users? To evaluate the coherence of the dependence syndrome elements for cocaine, factor analysis models are applied to the nine dichotomous DSM-III-R drug-dependence criteria derived from structured clinical interviews with 399 cocaine users. A single factor model, in which both the centrality and severity of each criteria were assessed, adequately describes the criteria and supports the coherence of the dependence syndrome concept for cocaine. Pre-occupation was the most central criterion in defining cocaine dependence. However, avoiding withdrawal through the use of other drugs measured the most severe level of drug dependence. Inability to stop using the tolerance were only minimally related to the measurement of cocaine dependence. PMID- 1751846 TI - Estimating drug consumption in opioid users: reliability and validity of a 'recent use' episodes method. AB - The efficient and accurate measurement of recent drug use is an essential component of treatment and research among opioid users. Urinalysis results alone will not give sufficient information to either the clinician or researcher, due to limitations in detection and an inability to distinguish extent of use. The present paper describes a 'recent use episodes method', adapted from the measurement of alcohol consumption, for obtaining self-reported drug use in eleven different drug categories. Reliability and validity data indicate that the method provides a quick means by which accurate information may be obtained on the overall recent drug use of opioid users. PMID- 1751847 TI - A scale for estimating the health status of opioid users. AB - The health status of injecting drug users has both clinical and research relevance. In order to evaluate the impact of treatments for opiate dependence on drug users' health status we need valid and reliable instruments which are short and easily administered by non-medical personnel. This paper describes the construction of a brief interviewer administered scale for assessing the current health status of injecting drug users. Data evaluating its reliability and validity are presented which indicate that the scale has excellent psychometric properties. PMID- 1751848 TI - Public support for warning labels on alcoholic beverage containers. AB - Warning labels are now required on alcohol beverage containers in the United States. Prior to the enactment of the warning label law, a random sample of adults in the general population of the United States were interviewed by telephone to assess baseline knowledge and support for the warning labels (n = 2006). This paper proceeds on the assumption that public support is crucial for sustained success of alcohol control policies such as the warning label mandate. We found that a vast majority (87%) of the respondents felt that alcoholic beverages should have warning labels about possible health hazards, with abstention as the most significant predictor of support. A majority of the respondents also felt that alcohol education, server intervention, treatment and counter-advertisement programs should be increased. A large minority felt that alcohol taxes should be increased store hours should be decreased, and the legal drinking age should be increased. Most respondents agreed that warning labels would not have much effect on heavy drinkers. When compared to responses to similar questions about alcohol control policies over the past 20 years, evidence supporting a conservative trend towards alcohol in the United States was found. PMID- 1751849 TI - Problem drinking and family history. AB - Data on SADQ, GHQ, disciplinary, financial and relationship problems were collected from 103 problem drinkers and 96 controls. Problem drinkers were significantly more severely affected than controls on all measures except financial problems. Of the problem drinkers, 55% had a positive family history, and this group were more severely affected on SADQ, GHQ and financial problem measures than family history negative subjects. The most severely affected group were those with a positive family history who also reported significant childhood problems, and the least affected were those without a family history who did not report significant childhood problems. PMID- 1751850 TI - Tobacco advertising restrictions, price, income and tobacco consumption in OECD countries, 1960-1986. AB - Factors affecting tobacco consumption per adult in 22 countries of the OECD between 1960 and 1986, were studied using pooled cross-section time-series analysis. The resulting log-linear model was estimated using Generalized Least Squares. The severity of tobacco advertising restrictions in each country and year was scored from published legislation and information from health agencies. Tobacco advertising restrictions have since 1973 increasingly been associated with lower tobacco consumption. Lower consumption levels were also associated with higher real tobacco prices, and with increased female labour force participation. Higher levels of consumption were associated with higher per capita real income and with a larger fraction of tobacco consumed as manufactured cigarettes. The model explains 99.5% of the variance in the average annual level of tobacco consumption across these countries. Ten-fold differences in purchasing power for tobacco products were found across the countries and years studied. In all countries tobacco products became more affordable between 1960 and 1986. In 1986 either a 36% inflation-indexed increase in real tobacco prices, or legislation to end tobacco promotion in those countries without a total ban, would have lowered average consumption by 6.8% and both together, by 13.5%. Across the OECD, if in 1986 all governments had raised tobacco product prices relative to income to Irish levels, and had banned all tobacco promotion, tobacco products consumption per adult would have fallen by 40% in that year. PMID- 1751851 TI - HIV and human rights. PMID- 1751852 TI - HIV infection in London. PMID- 1751853 TI - Personality disorder in perspective. AB - Personality disorders have for many years been on the fringe of psychiatry, with considerable doubts expressed about the usefulness, implications and validity of the concept. It is argued here that developments in the past few years have brought personality disorders into the mainstream of psychiatric practice. In particular, the recognition that personality function can be separated usefully from clinical symptoms, and that both mental state and personality can be disordered simultaneously, has led to better assessment and understanding. Advances in the classification, epidemiology, treatment and prognosis of personality disorders show that these conditions are common, extensive in their pathology, and cause much suffering. They cannot be ignored or dismissed as peripheral to psychiatry for they are an essential part of good psychiatric practice. PMID- 1751854 TI - Delusional memories: first-rank symptoms? PMID- 1751855 TI - Some aspects of family interventions in schizophrenia. I: Adherence to intervention programmes. AB - Although family intervention programmes to instruct relatives in management and coping skills are often effective in reducing schizophrenic relapse, many families either fail to be engaged or withdraw from treatment at an early stage. Some possible reasons for this are described and some suggestions for increasing adherence are made. Adherence with interventions may be viewed as a complex behaviour pattern, and factors increasing or decreasing the probability of such behaviour occurring and being maintained can and should be investigated to maximise the clinical potential of family intervention programmes. PMID- 1751856 TI - Some aspects of family interventions in schizophrenia. II: Financial considerations. AB - The direct costs to the mental health services for patients who participated in a trial of a behavioural family intervention to reduce schizophrenic relapse were estimated. Comparisons were made between two patient groups from households of high expressed emotion (HEE): one group received a nine-month family intervention (HEE Intervention) and the other group routine treatment (HEE Control). A third group consisted of patients from low-EE households (LEE Control). The significant decrease in relapse rates in the HEE Intervention group compared with the HEE Control group has previously been reported; the analysis of costs indicates that any increase in costs due to the family intervention is outweighed by a decrease in usage of the established mental health services. The intervention resulted in a decrease of 27% in mean cost per patient. PMID- 1751857 TI - Schizophrenia, bipolar disorder and depression. A discriminant analysis, using 'lifetime' psychopathology ratings. AB - Discriminant and canonical variate analyses were performed using 302 patients, on whom ratings of lifetime psychopathology and course of illness has been made. DSM III diagnoses were used to form the criterion groups. Bipolar disorder emerged as a distinct grouping, but there are reasons for dissatisfaction with its definition. The remaining patients formed a 'schizodepressive continuum', but this also had a tendency to bimodality. It is possible that the distinction between schizophrenia and depression was obscured by inadequacies in the data and the inclusion of excessive numbers of patients with schizoaffective depression in this study. PMID- 1751858 TI - Negative symptoms in chronic schizophrenia. Relationship to duration of illness. AB - The frequency and distribution of negative symptoms in a sample of 40 patients admitted to hospital with RDC-definite schizophrenia were examined. There was a highly significant positive correlation between negative symptom scores obtained using three different rating scales, but the presence of negative symptoms was not significantly related to duration of illness or number of episodes of illness. These findings do not support a model of negative symptoms being the consequence of schizophrenic relapse, but are in favour of their being an integral component of the schizophrenic syndrome, as salient in the first as in later episodes. PMID- 1751859 TI - Douglas House. Seven years' experience of a community hostel ward. AB - Of 24 residents of a ten-bed, community-based hostel ward suffering chronic psychiatric illness, nine have been resettled in the community, with four more expected to follow them. Five residents have made Douglas House their home but another six have manifested behavioural disturbance necessitating return to hospital wards. We found community discharge to be associated with illnesses having good prognostic features, while organic illness militated against such placement. Indicators of a prior history of behavioural disturbance seem to predict difficulties in managing a patient in this environment. PMID- 1751860 TI - Sleep electroencephalography in depressive illness. A collaborative study by the World Health Organization. AB - Eight WHO research centres from Europe, North America and Asia took part in a WHO study aimed at assessing the reliability and consistency of sleep-EEG abnormalities in major depression. Each centre was asked to include in the study ten depressed patients aged 20-65 years meeting the Research Diagnostic Criteria for a major depressive disorder, and to match them by age and gender with ten controls. There were 67 patients and 66 controls included in the study. Compared with controls, depressed patients showed sleep-continuity disturbances such as increase in sleep-onset latency, and decrease in total sleep time and in sleep efficiency. Stages 2 and 3, as percentages of total sleep time, were reduced in depressed patients, REM latency was shortened and REM density increased. These findings confirm the presence of specific sleep-EEG abnormalities in major depression. PMID- 1751861 TI - Suicide among adolescents in Greece. AB - The mean suicide rate among 10-19-year-olds in Greece from 1980 to 1987 was 0.98/100,000 per year (male 1.07, female 0.89). Girls and boys demonstrated the greatest suicide rate at 16 and 19 years, respectively. The combined suicide rate was significantly higher in the rural areas (1.48) than in Athens (0.48) and the other urban areas (0.98). Boys committed suicide more frequently than girls in Athens and other urban areas, whereas girls did so in the rural areas. The suicide rate declined during the last three years of the study. Differences in the methods used and the reported reasons for suicide were observed among the adolescents in Athens, other urban areas, and the rural areas. Greek adolescents appear to be relatively protected from suicide, particularly those who live in the urban areas. PMID- 1751862 TI - Psychiatric manifestation of systemic lupus erythematosus in Singapore. A cross cultural comparison. AB - In a case-control, cross-cultural study of the psychiatric morbidity of systemic lupus erythematosus in an Oriental population, 30 patients suffering from SLE and 29 controls with rheumatoid arthritis were interviewed. The SLE patients in Singapore exhibited greater psychiatric morbidity than their Western counterparts. Significant correlation was observed between psychiatric morbidity and the clinical disease activity. The patient's perception of the severity of arthritis, myalgia and dermatological lesions was an important aetiological factor. Culturally determined, disease-related psychological stresses also contributed to the psychopathology. PMID- 1751863 TI - A family with multiple instances of definite, probable and possible early-onset Alzheimer's disease. AB - A family with a multigenerational history of proven or suspected early-onset Alzheimer's disease (AD) consistent with autosomal-dominant inheritance is described. To date, the pedigree comprises five generations in which there are 13 known affected individuals. The mean age of onset of cognitive deficits in those for whom data are available (n = 11) is 47.6 (s.d. 3.0) years and the mean age of death (n = 10) is 58.8 (s.d. 4.0) years. The variability in the extent and quality of available data illustrates the diagnostic difficulties encountered in ascertaining such an extended pedigree, and the need for caution in interpreting the evidence. PMID- 1751864 TI - Phobic disorders in the elderly. AB - Sixty confirmed cases of phobic disorder identified in an urban elderly community sample were compared with 60 controls matched pairwise for age and sex. Cases reported higher rates of specific and non-specific neurotic symptoms, and all were assigned to a diagnostic CATEGO class, compared with seven of the controls. A past history of chronic psychiatric disorder other than phobia was commoner in the cases. Most cases had more than one fear; agoraphobic main fears were predominantly of late onset and associated with moderate to severe social impairment, whereas specific main fears were associated with early onset and minimal social impairment. The onset of agoraphobic fears in old age was attributed by most cases to an episode of physical illness or other traumatic event. Increased rates of palpitations, dyspnoea, giddiness and tinnitus not attributable to anxiety were identified in the cases. Cases did not differ from the controls in socio-economic status, or in the number or quality of current intimate confiding relationships, but they reported higher rates than controls of parental loss before the age of 18 years. Cases reported higher rates of contact with general practitioners, but only one was in contact with psychiatric services at the time of interview. Cases also reported receiving more help in personal care from family members. PMID- 1751865 TI - Causal attributions and psychiatric symptoms in survivors of the Herald of Free Enterprise disaster. AB - The aim of the present study was to explore the relationship between causal attributions and psychiatric symptoms in those who survived the capsizing of the Herald of Free Enterprise ferry, two years following the disaster. Internal and controllable attributions for disaster-related experience are strongly related to poorer psychological outcome. PMID- 1751866 TI - Reactions of police officers to body-handling after a major disaster. A before and-after comparison. AB - This study reports the results of an unusual opportunity to follow up a group of police officers who were involved in body-handling duties following the Piper Alpha disaster, and for whom there were available data from pre-disaster assessments. In addition, after these duties, the officers were compared with a matched control group of officers who had not been involved in such work. The comparisons failed to demonstrate high levels of post-traumatic distress or psychiatric morbidity. The results are interpreted in terms of issues such as the officers' own coping strategies, and major organisational and managerial factors. PMID- 1751867 TI - The 1978 Italian mental health law--a personal evaluation: a review. AB - "The author discusses the sociopsychiatric consequences of the 1978 Italian mental health law. He also reviews the international scientific ideas that led up to it. The sociopolitical psychiatric views of the late Franco Basaglia, pioneer of the change in the mental health system of the Italian Republic, are described. Statistical reports and critical analyses are reported. Objective data, based on the author's personal experience as a practising psychiatrist in Rome, Italy, from 1969 to 1987, are given." PMID- 1751868 TI - The prevalence of eating disorders in recently admitted psychiatric in-patients. AB - Of 107 recently admitted psychiatric patients screened for eating-disorder symptoms by questionnaire, 17% met DSM-III-R criteria for eating disorders. Eight patients (one male) had bulimia nervosa. Ten patients had eating disorder not otherwise specified: seven (three male) bulimic type, and three (one male) anorexia nervosa type. The most common concurrent diagnoses were mood and personality disorders. As eating-disorder symptoms are relevant to the diagnosis and management of other psychiatric disorders they should be assessed routinely in all psychiatric patients. PMID- 1751869 TI - Effect of caffeine intake on psychotic in-patients. AB - Psychotic in-patients who consume caffeine may present complications in the course of their illness. Two cases are described which illustrate the clinical profile of such patients, whose caffeine-associated complications are often misdiagnosed. PMID- 1751870 TI - Recurrence of puerperal psychosis during late pregnancy. AB - Two cases of pre-partum psychosis are described. Both patients had previous episodes of puerperal psychosis but no non-puerperal illnesses. The possible relationship of pre-partum and post-partum psychosis is discussed. PMID- 1751871 TI - Psychotropic drug use in medical and surgical wards of a teaching hospital in northern Nigeria. AB - The overall prescription rate of psychotropic drugs in a Nigerian teaching hospital was 33.1%. This was slightly higher among surgical than medical patients. It is suggested that more attention needs to be paid to psychotropic drug education in developing countries in order to ensure a more rational use of these drugs. PMID- 1751872 TI - Neuroleptic malignant syndrome secondary to loxapine. AB - Loxapine was introduced to the British market two years ago although it has been used in North America for eight years. We report the first probable case of neuroleptic malignant syndrome (NMS) secondary to loxapine in Britain. Two previous cases have been reported in North America (manufacturer's data). PMID- 1751873 TI - Suspicion of somatoform disorder in undiagnosed tabes dorsalis. AB - We present a case of tabes dorsalis, which consisted of intermittent, sharp pains and diffuse neurological abnormalities, and was initially considered to be a somatoform disorder. The unusual behavioural presentations of neurosyphilis may lead to premature psychiatric diagnoses. It is thus important that psychiatric consultants be aware of the myriad manifestations of the disease. PMID- 1751874 TI - Sleep-loss as a possible mediator of diverse causes of mania. AB - When sleep duration and mood were monitored longitudinally in a 59-year-old woman with bipolar illness, sleep loss appeared to mediate the triggering of mania by psychosocial and pharmacological precipitating factors. This interpretation was supported by observations that mania could repeatedly be induced experimentally by depriving her of sleep for one night. The patient's data illustrate how sleep loss might be a preventable cause of mania in a variety of situations. PMID- 1751875 TI - Money hidden and rediscovered in subsequent manic phases. A case of action dependent on mood state? AB - A manic-depressive patient hid 3000 pounds during one manic phase and subsequently, when his mood stabilised, could not remember where he had hidden it. He found the money during a subsequent manic phase a few months later. We suggest that this is not a clear case of state-dependent memory, since the patient at no point explicitly recollected where he had hidden the money. Instead we suggest that this represents state-dependent action. The links between this case and previous research on state-dependent memory are outlined. PMID- 1751876 TI - Withdrawal from heroin and methadone. PMID- 1751877 TI - Psychogenic amnesia? PMID- 1751878 TI - Portrayal of women in advertisements. PMID- 1751879 TI - Winnicott's contribution. PMID- 1751880 TI - Incidence rates of schizophrenia. PMID- 1751881 TI - Ethnic nomenclature. PMID- 1751882 TI - Pathological jealousy defined. PMID- 1751883 TI - Access to health records. PMID- 1751884 TI - Anorexia nervosa in Asian children. PMID- 1751885 TI - The clinical application of restricted environmental stimulation therapy (REST): observations of a psychiatrist. PMID- 1751886 TI - Is oncogene activity involved in the alcohol withdrawal syndrome? PMID- 1751887 TI - Politically motivated suicides. PMID- 1751888 TI - NMS and genetic drug oxidation. PMID- 1751889 TI - Reading about ... sex therapy. PMID- 1751890 TI - Underwater medicine: a neglected area in Accident and Emergency specialist training. AB - We have evaluated the available medical care to sports divers by a postal questionnaire sent to consultants and senior registrars in Accident and Emergency medicine in the UK, assessing their training in underwater medicine. Replies were received from 60 of 96 consultants (63%) and 32 of 58 (55%) senior registrars. Thirty-two per cent of consultants and 50% of senior registrars had previous personal experience in managing an underwater diving accident. Thirty per cent of consultants and only 19% of senior registrars had prior formal postgraduate training in underwater medicine. Twenty-seven per cent of consultants and 13% of senior registrars replying did not know the pattern of referral for specialist advice nor where the nearest recompression chamber was to be found. We believe that more formal postgraduate training in underwater medicine is needed by A and E medical staff. Furthermore, clear guidelines about emergency management and patterns of referral for diving accidents should be displayed prominently in all A and E departments. PMID- 1751891 TI - Hazards of horse-riding as a popular sport. AB - The increasing incidence of horse-riding accidents, which are often severe in nature, prompted a pilot study of a questionnaire designed to elucidate the cause of such accidents. It was hoped that, on a larger scale, the information gleaned would highlight possible preventative measures which might improve the safety of an important recreational pursuit enjoyed by young and old from many walks of life. A retrospective study of riders sustaining serious spinal injuries admitted to Stoke Mandeville Hospital was compared with riders sustaining minor but significant injuries as the accidents came to the attention of the authors. The detailed analysis paid particular attention to the setting and to the experience and task of horse and rider. It was found that 70% of the 20 accidents could be thought attributable to the behaviour of the horse at the time, and seven of these were in the spinal injuries group. Rider error was a significant contribution in seven cases, and in two instances the rider was under instruction at the time. There was also inadequate experience of the rider in seven cases, of which five were thought to show inadequate supervision. The limited number of cases studied precludes significant observations, but, as the majority of accidents seemed preventable, a larger study has been initiated in collaboration with the British Horse Society. PMID- 1751892 TI - Sports clinics and hospital trusts. PMID- 1751893 TI - Human chorionic gonadotrophin and sport. AB - Human chorionic gonadotrophin (hCG) is a glycoprotein hormone which is produced in large amounts during pregnancy and also by certain types of tumour. The biological action of hCG is identical to that of luteinizing hormone, although the former has a much longer plasma half-life. Some male athletes use pharmaceutical preparations of hCG to stimulate testosterone production before competition and/or to prevent testicular shutdown and atrophy during and after prolonged courses of androgen administration. Testosterone administration can be detected by measuring the ratio of concentrations of testosterone to epitestosterone (T/E). An athlete is often considered to have failed a drug test if the urinary T/E ratio is greater than 6. In contrast, hCG administration stimulates the endogenous production of both testosterone and epitestosterone without increasing the urinary T/E ratio above normal values. Although the administration of hCG was banned by the International Olympic Committee (IOC) in 1987, no definitive test for hCG has been approved by the IOC. Currently, the only way of measuring small concentrations of hCG is by immunoassay, and this does not have a discriminating power as great as gas-liquid chromatography with mass-spectrometry which is necessary to satisfy IOC requirements. Extraction procedures and chromatographic steps could be introduced before using a selected immunoassay for hCG to meet these requirements. PMID- 1751894 TI - Protecting the sportsman's brain (concussion in sport). Annual guest lecture 1990, London Sports Medicine Institute. PMID- 1751895 TI - Ice hockey injuries: incidence, nature and causes. AB - In this prospective study, we have investigated incidence of injuries of different severity, types of injury, and mechanisms of injury during ice hockey games. All twelve Swedish elite hockey teams were observed during the season 1988 1989 when a total number of 664 games were played. There was a total number of 285 injuries, of which the majority were minor (61%) and only 9% were classified as major. Seventy-four per cent of the injuries occurred during games and 26% during practice. The overall incidence of injury was 53.0 per 1000 player-game hours. Eighty-five per cent of injuries were caused by trauma and 15% by over use. Injuries were most often localized to the head/face (39%) or the lower limb (32%). Most injuries resulted from stick contact or player contact including checking. A reduction of minor and moderate injuries should be possible by stricter enforcement of the hockey rules, and more widespread use of visors. PMID- 1751896 TI - Factors affecting adherence of end-stage renal disease patients to an exercise programme. AB - Recently it has been shown that regular exercise is both physiologically and psychologically beneficial to patients with end-stage renal disease (ESRD). However, ESRD patients traditionally have a high non-adherence level to their self-care and medical regimens. To date, their adherence to exercise programmes has not been studied. Background information about employment, medical history, previous exercise habits and locus of control was obtained from 40 volunteer ESRD patients who started exercise at home. Twenty-eight participants maintained the exercise programme, consisting of aerobic activity lasting an average of 25 min, four times per week, for 12 weeks. The adherent patients were found to have encouraging support groups (75 versus 25%), to be between 41 and 60 years of age (64 versus 33%), to have been on dialysis for between 2 and 5 years, and to have loci of control (feeling of control over life events) classed as 'internal' (68 versus 25%). Factors such as sex, race, employment status and depression were found to have little influence on adherence. The major finding of this study was that patients adherent to exercise could be distinguished by unique psychological and psychosocial factors, and that adherence in this population was higher (70 compared with 50%) than some estimates for the general population. PMID- 1751897 TI - Meniscotibial ligament strains: a prospective survey. AB - Medial knee pain is an increasingly common presentation in sports medicine practice. A prospective review was undertaken of 72 patients, mean age 48 years, seen in 1986-1987. The physical findings which were most diagnostic were a loss of some degrees of flexion which was painful medially when forced, and tenderness over the posteromedial joint line. Treatment was either injection of local steroid, or physiotherapy, together with emphasis on quadriceps exercise. Five patients failed to respond and were referred for arthroscopy. Nine patients relapsed once but no subsequent episode has occurred. Meniscotibial ligament strain is a common cause of knee pain in middle-aged sports people. PMID- 1751898 TI - Comparison of clinical tests and the KT1000 in the diagnosis of anterior cruciate ligament rupture. AB - A prospective study was undertaken to compare the accuracy of the Lachman test, anterior drawer test and jerk test with the KT1000 knee arthrometer in patients with proven anterior cruciate ligament deficiency. The Lachman and anterior drawer tests were found to be the most accurate indicators of anterior cruciate ligament deficiency. The KT1000 knee arthrometer was found to be totally inaccurate, which precludes its use as an objective measure of anteroposterior laxity of the knee. PMID- 1751899 TI - Paragliding injuries. AB - Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries. PMID- 1751900 TI - [Transcranial Doppler ultrasound]. AB - Over the last decade, transcranial Doppler examination of the cerebral vessels has been made possible by the development of a high-intensity, low-frequency (2 MHz) pulse probe. The middle, the anterior and the posterior cerebral arteries, the cavernous portion of the carotid artery and the basilar artery can thus be easily studied transtemporally or transorbitally or from below the foramen magnum. The transcranial Doppler examination is already used clinically to study arteriosclerosis and in the diagnosis and follow-up of vasospasm and arteriovenous malformations. This review describes the examination procedure and summarizes and illustrates its major indications. PMID- 1751901 TI - Computed tomography of the knee. AB - Although magnetic resonance imaging (MRI) has become the imaging technique of choice in Canada and elsewhere in the evaluation of knee disorders, magnetic resonance units are frequently unavailable, or access to them is greatly restricted. The authors have found that computed tomography (CT) can sometimes be successfully substituted for MRI as a noninvasive method for imaging a wide variety of knee disorders. This article reviews the CT appearance of normal knee anatomy and illustrates a wide variety of pathological conditions that can be successfully evaluated. PMID- 1751902 TI - Physician payment reform: issues for Canadian radiologists. AB - Policy decisions taken by the US Congress in the 1980s to restrain health care costs included the designation of diagnostic-related groups, the creation of scales of relative value and legislation to introduce free-for-service payment to physicians in 1992; discrepancies in the system are to be corrected by 1996. Under federal contract a system of resource-based relative-value scales was created for all medical disciplines except radiology, which by special legislation prepared its own experience-based relative-value scale. The scales are based on magnitude estimation of the work of physicians and analyses of actual costs. Codes for medical services have been published, which include a weighting for each service in relation to all others. Multiplication by a conversion factor establishes the fee to be paid by the carriers acting for the Health Care Financing Administration. The relative values will be updated every 5 years. Publication of this information for US Medicare patients (the disabled, the elderly and those with end-stage renal disease) will likely have a profound effect on the physician payment system in Canada. Under the reformed system the lifetime earnings of all physicians will become more similar. Four problem areas are discussed in the paper: self-referral, administrative complexity, malpractice and the plight of those without medical coverage. Resolution of these problems is being actively sought. PMID- 1751903 TI - Panic disorder: vascular evaluation with transcranial Doppler ultrasonography. AB - Several recent studies have shown neurophysiologic and neuroanatomic abnormalities in panic disorder. This study aimed to assess by transcranial Doppler (TCD) ultrasonography the magnitude of the changes in blood flow during panic attacks induced by intravenous sodium lactate infusion. The subjects consisted of 30 patients with panic disorder (DSM-III-R) and 25 controls; all were between the ages of 18 and 40 years and were right-handed. The flow in the middle cerebral artery was recorded bilaterally before the infusion began (to provide baseline readings) and at 3-minute intervals during the infusion. The patients showed a more rapid acceleration of flow (p less than 0.05) than the controls. Higher maximal velocity and higher variations in velocity (p less than 0.05) were observed in the patients sensitive to lactate but only in the right middle cerebral artery. These results suggest that abnormalities of local cerebrovascular autoregulation occurred in the patients with panic disorder during attacks induced by sodium lactate. PMID- 1751904 TI - Portable scanning slit device for obese patients. AB - A portable apparatus with rotating scanning slits has been designed to reduce scatter in the radiographs of obese patients. Rotating scanning slit radiography reduces scatter efficiently, but previous instruments with linear or curved slits have been too heavy to be portable. The author's "dart-board" pattern of multiple sector-shaped holes is theoretically efficient at reducing scatter, compensates for potential ring artifacts by overlapping the holes and expands the holes in the lower plate to account for penumbra. Computer simulation with Monte Carlo techniques shows that the new design is free of concentric ring artifacts. This design should improve the quality of radiographs of very obese patients. PMID- 1751905 TI - Optimization of prostatic magnetic resonance imaging technique. AB - With a 1.5-T magnetic resonance imager the authors systematically varied a large number of technical factors to obtain an optimum balance between high image quality and reasonable imaging time for the prostate gland. Each parameter was adjusted relative to benchmark images of very high quality to achieve a reasonable acquisition time with as little loss of the signal-to-noise ratio (SNR) as possible. Image quality was judged subjectively by magnetic resonance radiologists and objectively by measurements of SNR for the prostate. The authors recommend multislice, multiecho spin-echo pulse sequences with dual surface coils, fat suppression, reduced bandwidth, a repetition time of 1500 ms, echo times of 30 and 60 ms, a flip angle of 60 degrees, two excitations, a slice thickness of 5 mm with a 1.5-mm gap and 192 phase-encoding steps. The acquisition time for one such series was 9.6 minutes. PMID- 1751906 TI - Isolated colonic hemangioma in a child. AB - Hemangiomas of the large bowel are very rare and usually occur in the rectosigmoid. A large cavernous hemangioma of the colon was demonstrated in a 9 month-old child who presented with recurrent lower gastrointestinal tract bleeding. Barium examination demonstrated an annular lesion of the hepatic flexure. Computed tomography demonstrated the extent of the lesion, and contrast enhancement suggested the vascular nature of the tumour before a laparotomy was performed to remove the tumour. PMID- 1751907 TI - Lingular opacity with an endobronchial mass. PMID- 1751908 TI - Restoration of the threadless Cope-Cook catheter. PMID- 1751909 TI - Dual technique for preoperative localization of nonpalpable breast lesions. AB - The combination of guide wire and dye techniques for preoperative localization of nonpalpable breast lesions is superior to either technique alone. The dye acts as a backup in the event of migration, transection or removal of the wire, which has occurred in 2 (1.3%) of 154 localizations of breast lesions at the author's institution. PMID- 1751910 TI - Residents' corner. Answer to case of the month #10. Malrotation of the small bowel with intermittent herniation and volvulus. PMID- 1751911 TI - Lacrimal canaliculoscopy: development of the instrument. AB - We have developed an endoscopic device for use in the lacrimal drainage system. The device employs a flexible, small-calibre fibreoptic cable that can easily negotiate the canalicular system. The device can be used in conjunction with a video camera and monitor for simultaneous viewing. The endoscope can be used alone for the diagnosis of lacrimal disorders. Possible future applications include laser treatment of lacrimal disorders. PMID- 1751912 TI - Retinal dialysis: lack of evidence for a genetic cause. AB - The author reviewed 150 cases of retinal detachment secondary to retinal dialysis. In 95 cases (63%) a definite history of ocular trauma was obtained. In 91% of the 45 cases with superonasal, superotemporal or inferonasal involvement there was a history or evidence of blunt injury, compared with 63% of the 105 cases with inferotemporal involvement. Review of the family history, eye examinations of close relatives and ophthalmoscopic follow-up of the fellow eye in the 35 cases of inferotemporal dialysis with no history or evidence of trauma ruled out a genetic basis for the dialysis. Forgotten or denied trauma or a nongenetic developmental anomaly were felt to be the cause of the dialysis in these cases. PMID- 1751913 TI - Cryopexy in pars planitis. AB - Cryotherapy has been reported to be of benefit in pars planitis. We studied 16 eyes with classic pars planitis unresponsive to corticosteroid therapy. Eight eyes continued with systemic and periocular steroid therapy, and in the remaining eight eyes transconjunctival cryopexy of the peripheral retina and vitreous base was done as an additional procedure. At 6 months four of the eyes that received cryopexy showed an improvement in Snellen visual acuity, and in the other four the acuity was unchanged; none of the eyes showed any vitreous base neovascularization. Among the eyes that received steroid therapy only, the acuity was unchanged in five, improved in one and reduced in two. PMID- 1751914 TI - Ocular motor apraxia following cardiac surgery. AB - Ocular motor apraxia is characterized by a deficiency in the generation of voluntary saccadic eye movements despite the presence of spontaneous saccades. We report two cases of isolated ocular motor apraxia, both in children, that developed following cardiac surgery. Electro-oculography was done in one case and showed slow saccades and decreased pursuit gain. The authors review the neuroanatomic and neurophysiologic features relevant to supranuclear gaze mechanisms. PMID- 1751915 TI - Metastatic choroidal choriocarcinoma: a clinicopathological study. AB - A previously healthy 33-year-old woman presented with decreased vision and pain in her left eye. Funduscopic examination revealed a mass in the posterior pole of the eye, and chest radiography showed a lesion in the lower lobe of her left lung. The eye became painful and blind over 12 days and was enucleated. The tumour had the typical histopathological and immunohistochemical features of choriocarcinoma: sheets of cytotrophoblasts with pleomorphic nuclei and lacy cytoplasm intermingled with multinucleated syncytiotrophoblasts. The neoplastic cells stained positively for cytokeratin and the beta subunit of human chorionic gonadotropin (beta-HCG). The serum beta-HCG level was markedly elevated, at 82,000 (normally less than 5) IU/L. The patient was treated with combination chemotherapy, and normal serum beta-HCG levels were obtained. Thirty months after presentation the serum beta-HCG level was normal and there had been no clinical evidence of recurrence. To our knowledge this is the second case of metastatic choriocarcinoma in the eye in which the ocular tumour caused the presenting symptom. PMID- 1751916 TI - Gastric linitis plastica metastatic to the uvea. AB - A 59-year-old man underwent total gastrectomy for diffuse, poorly differentiated gastric adenocarcinoma diagnosed as linitis plastica. Loss of vision in the right eye 5 months later due to extensive choroidal tumours was the first indication of metastatic disease. Radiologic studies showed multiple bony metastases. The blind, painful eye was enucleated. Pathological examination of the globe showed massive metastatic mucus-secreting adenocarcinoma of the choroid, with positive immunohistochemical staining for carcinoembryonic antigen (CEA) of the foci of the more highly differentiated neoplastic cells. The plasma CEA level had been normal. The patient died 3 months after enucleation from metastatic disease. PMID- 1751917 TI - Adenoma of the nonpigmented epithelium of the ciliary body. AB - A 56-year-old man presented with a left ciliary body mass, anterior vitreous hemorrhage and a subluxed, cataractous lens. The clinical course included rapid enlargement of the mass, anterior uveitis, cataract progression and secondary glaucoma. Investigation included fluorescein angiography, ultrasonography and computed tomography. The eye was enucleated because of progressive enlargement with poor vision and uncontrolled secondary glaucoma. Histopathological examination showed an adenoma of the nonpigmented ciliary epithelium with cystic areas of hyaluronidase-sensitive acid mucopolysaccharide. The mass distorted the iris, occluded the angle structures and produced a complete cataract. The basement membrane of the adjacent ciliary processes was extensively thickened. The authors discuss the clinical association with vitreous hemorrhage and the local damage caused by this benign tumour. PMID- 1751918 TI - Dog and human bites of the eyelid repaired with retrieved autogenous tissue. AB - Two cases of traumatic avulsion of the upper eyelid were surgically repaired with retrieved autogenous tissue. Both injuries were caused by bites, canine in one case and human in the other. Surgical repair consisted of debridement of the retrieved tissue and layered closure of the wound 17 and 40 hours after the injury occurred. Good functional results were obtained in both cases. In both patients mild lid retraction and loss of cilia were noted. One of the patients underwent a secondary lid-lengthening procedure with scleral grafting for optimal cosmesis. PMID- 1751919 TI - Malpractice crisis is easing, if only slightly. PMID- 1751920 TI - A need for evaluation. PMID- 1751921 TI - Women and academic medicine. PMID- 1751922 TI - Medical training in the United States. PMID- 1751923 TI - Nutrients as modulators of immune function. PMID- 1751924 TI - Generic drug companies are the winners. PMID- 1751925 TI - Stress and the ethical physician. PMID- 1751926 TI - Psychiatrists confront an image problem. PMID- 1751927 TI - Recruiting ambulance volunteers: rural physicians can help. PMID- 1751928 TI - Periodic health examination, 1991 update: 6. Acetylsalicylic acid and the primary prevention of cardiovascular disease. Canadian Task Force on the Periodic Health Examination. PMID- 1751929 TI - Snowboarding injuries: an analysis and comparison with alpine skiing injuries. AB - OBJECTIVE: To analyse the types and causes of injuries associated with recreational snowboarding and to compare these with the injuries seen in alpine skiing. DESIGN: Prospective case series. SETTING: Rural hospital near three large ski resorts. PATIENTS: All people presenting to the Emergency Department with an injury caused by snowboarding during two ski seasons (1988-90). Of the 115 injured snowboarders identified, 73 (63%) completed the questionnaire. Information on the other patients was obtained from the hospital emergency records. Information was also obtained on seven alpine skiers who collided with snowboarders. RESULTS: Of the snowboarders 87 (76%) were male, and the mean age was 20.3 years. A total of 132 injuries were documented. Of the respondents to the questionnaire 83% reported that their fitness level was excellent or above average, 36% had never been on a snowboard previously, 25% were in their first year of snowboarding, 39% reported excellent snow conditions, 59% reported light traffic on the hill, and 7% had consumed alcohol before their accident. Injuries were equally divided between the upper body and the legs, 75% of the lower-limb injuries involving the left (lead) leg. Significant differences were noted between the patterns of injuries in snowboarding and alpine skiing: snowboarders were less likely to have lacerations (0% v. 8% respectively), boot-top contusions (0% v. 4%), thumb injuries (1% v. 10%) and knee sprains (14% v. 27%) and more likely to have spinal injuries (12% v. 4%), foot or ankle injuries (28% v. 5%) and distal radius fractures (10% v. 1%). CONCLUSIONS: Snowboarding is associated with a unique pattern of injuries, the knowledge of which could influence snowboarder education, accident prevention and equipment design. Additional research is needed to understand better the types, causes and rates of injury associated with snowboarding. PMID- 1751930 TI - Use of acetylsalicylic acid by physicians and in the community. AB - OBJECTIVE: To determine physicians' attitudes toward prescribing acetylsalicylic acid (ASA), physicians' own use of ASA and the prevalence of ASA use in the community following the trials of ASA for primary prevention of coronary heart disease. DESIGN: Random sample surveys of physicians and the general public by mail and telephone respectively and a mail survey of a selected panel of expert cardiologists and neurologists. SETTING: London, Ont., and surrounding Middlesex County. PARTICIPANTS: A total of 210 physicians (77% of eligible subjects), including family practitioners and most types of specialists, with an active medical licence and 666 English-speaking people (75% of eligible subjects) aged 18 years or more living in a household with active, listed telephone service. MAIN OUTCOME MEASURE: Long-term ASA use (at least 80 mg on alternate days for 4 or more consecutive weeks) for the treatment of atherosclerosis. MAIN RESULTS: Sampled physicians and experts agreed that long-term ASA therapy was indicated in patients with unstable angina, a transient ischemic episode or recent myocardial infarction but not for primary prevention in healthy middle-aged men and women at low risk for ischemic vascular disease. Both groups were uncertain about the role of ASA in primary prevention in asymptomatic people with risk factors for atherosclerosis. Nine (16%) of the 55 male physicians aged 50 years or more took ASA routinely for primary prevention. In the community survey almost all those who used ASA routinely were 50 years or older. The proportions of men and women in this age group who used ASA routinely for any reason were 19% (95% confidence limits [CLs] 11 and 28) and 14% (95% CLs 8 and 19) respectively; the proportions of men and women who used ASA routinely and apparently for primary prevention were 8% and 1% respectively. A total of 43% (95% CLs 30 and 57) of those with apparent ischemic vascular disease took ASA routinely. Medically unsupervised long-term ASA use for primary or secondary prevention of ischemic vascular disease was uncommon (reported by 2% of those who used the drug routinely). CONCLUSIONS: Physicians generally agree on a role for long-term ASA therapy in the secondary prevention of ischemic vascular disease. However, the prevalence of long-term ASA use in people with overt atherosclerosis in the community may be less than optimal. The role of the drug in the primary prevention of ischemic vascular disease is less accepted. Long-term ASA use in the community for primary prevention is uncommon but detectable. PMID- 1751931 TI - Moth-associated dermatitis in Canadian travellers returning from Mexico. PMID- 1751932 TI - Nutritional management of chronic renal disease. PMID- 1751933 TI - The work of a stationary hospital in the field. 1919. PMID- 1751934 TI - Safety of polyurethane-covered breast implants. Expert Panel on the Safety of Polyurethane-covered Breast Implants. PMID- 1751935 TI - Major Mustard and me. PMID- 1751936 TI - More Canadian MDs showing interest in US practice, but entry isn't quick or easy. PMID- 1751937 TI - Crossing the border to practise is no guarantee of happiness or success. PMID- 1751938 TI - In a greying Canada, hospice care is the wave of the future. PMID- 1751939 TI - The Civil War comes to Queen's. PMID- 1751940 TI - Side effects during long-term treatment with depot antipsychotic medication. AB - During long-term treatment of schizophrenia with antipsychotic medication, side effects such as weight gain and tardive dyskinesia may develop, while other extrapyramidal side effects may continue. A large multicenter, double-blind, comparative trial of haloperidol decanoate and fluphenazine decanoate has been completed, in which 181 patients took part. The study lasted for 1 year and patients were assessed using the Krawiecka scale, the Montgomery-Asberg scales for schizophrenia and depression, the Simpson-Angus scale for parkinsonism, the AIMS for tardive dyskinesia, and a scale for akathisia. Patients were also weighed at each assessment. The results provide further evidence about the occurrence of weight changes, extrapyramidal side effects, and depression during long-term treatment and about the relative benefits of the two treatments. PMID- 1751941 TI - Reproducibility of an oral cancer and precancer detection program using a primary health care model in Sri Lanka. AB - A pilot feasibility study utilizing primary health care workers (PHCW) in the early detection of oral cancer and precancer was reported in 1984. The present study was to assess the reproducibility of this model in a different geographic area using existing Government Health Services. In order to improve the compliance of individual referrals following detection (54% in the previous study) a simultaneous health education program was mounted. Of 72,867 villagers aged 20 years and over who were allocated for screening, 57,124 (78%) were examined during 1 year by 36 PHCWs. Oral lesions were detected in 3559 (6.2%). Of these, 2193 (62%) complied by presenting for a reexamination at the hospital. Twenty new cancers and 1716 subjects with oral precancerous lesions were confirmed. While the population screening coverage achieved was higher than in the feasibility study, compliance was marginally improved. Noteworthy, however, was the detection of 20 new cancers as compared to 4 in the feasibility study. This primary health care model for cancer detection appears to be organizationally feasible for a developing country. PMID- 1751942 TI - Management of oral mucosal dysplasia with beta-carotene retinoic acid: a pilot cross-over study. AB - Mucosal dysplasia in the head and neck region is recognized to be a precancerous lesion. Between January 1983 and December 1987, a pilot study was conducted at the Manitoba Cancer Treatment and Research Foundation to determine the effects of beta-carotene and cis-retinoic acid on mucosal dysplasias. Eighteen patients were treated with a "cross-over" regimen. The overall response to treatment was 61%, with 33.3% complete responses. Patients who smoked had a significantly better response than nonsmokers. The response rate for 9 of 11 smokers was 81.2%, and 2 of 7 nonsmokers or 28.6% responded to this protocol. The beneficial effect of these drugs should be established by prospective, randomized trial in high risk populations. PMID- 1751943 TI - Retinol and retinol-binding protein in lung cancer screening. AB - Human epidemiology studies demonstrate an inverse correlation between serum levels of vitamin A and the incidence of lung cancer. While such studies suggest that vitamin A may have a role in cancer prevention, the intent of this study was to investigate the use of vitamin A status parameters as markers for detection of occult lung cancer. In the first of two phases of this study, we established criteria for a prospective screening study. Serum levels of retinol-binding protein (RBP), zinc, retinol, and beta-carotene in lung cancer patients were compared to levels in controls. For the second phase, a prospective screening study, 100 ambulatory male cigarette smokers over the age of 45 were enrolled. Subjects were excluded if they had a known diagnosis of cancer, recent weight loss, or serum albumin less than 3.5 g/dl. Subjects with RBP less than 4.2 mg/dl and retinol less than 42 micrograms/dl were classified as high-risk; those remaining were classified as controls. A chest X-ray (CXR) was obtained on all 17 high-risk subjects and on 26 of the 83 controls. CXR was read and follow-up was performed by physicians without knowledge of this study. Lung cancer was detected in 24% (4/17) of the high-risk subset, and 4% (1/26) of the controls. These data suggest that retinol and RBP may be useful in lung cancer screening for selecting a high-risk population that warrants further examination. PMID- 1751944 TI - Smoking and other risk factors associated with the stage and age of diagnosis of colon and rectum cancers. AB - The present study analyzes data on colon and rectum cancer cases from a population-based cancer registry to determine the effect of smoking, alcohol drinking, and family history of cancer on disease characteristics. A total of 771 cases of primary invasive cancer of the colon and 304 cancers of the rectum constitute the study sample. More advanced colon cancer was present in female smokers than in female nonsmokers, while in males there was no smoking effect on stage at diagnosis of colon cancer. For cancer of the rectum, male smokers had a higher frequency of advanced disease than did nonsmokers. Smoking men and women were found to have lower mean ages at diagnosis of both colon and rectum cancer than did nonsmokers (p less than 0.001 and p less than 0.004, respectively). Alcohol drinking remained consistently associated with lower age at diagnosis in both sexes for both colon and rectum cancer (p less than 0.001 and p less than 0.001, respectively). Those cases of rectum cancer having positive family history for colorectal cancer in their first degree relatives had younger age at diagnosis than those having negative family history (p less than 0.005). The age at diagnosis was progressively younger as the number of risk factors increased (p less than 0.001 for colon cancer and p less than 0.003 for cancer of the rectum). Our findings indicate an interaction between exposures to risk factors that are potentially carcinogenic or cocarcinogenic and manifestations of cancer of the colon and rectum. PMID- 1751945 TI - Mass screening for colorectal cancer in Japan. AB - A mass screening program for colorectal cancer has been conducted in Japan for several years, and the nationwide statistics showed a total of 416,382 participants in 1988. This paper describes the present status of mass screening program for colorectal cancer in Japan and related issues as follows: annual trend of the number of examinees, age distribution of examinees, screening methods, diagnostic methods, evaluation of screening accuracy for fecal occult blood tests, and screening interval. PMID- 1751946 TI - International comparisons of nutrition and mortality from pancreatic cancer. AB - Average per capita consumption of eggs, milk, and meat; total caloric intake; and protein and fat consumption in 29 countries from 1964 through 1966 was related to the average age-adjusted mortality rates from cancer of the pancreas in these same countries for the period 1978 through 1979. A direct and significant correlation between mortality rates from cancer of the pancreas and per capita consumption of eggs, milk (p less than 0.001), and meat (p less than 0.01 for males and p less than 0.05 for females) was found. The total caloric intake was directly correlated with mortality rates from pancreatic cancer (p less than 0.01). This correlation was stronger for calories derived from animal sources of food (p less than 0.001) for both sexes, while consumption of vegetable calories correlated with decreased rates of mortality from pancreatic cancer. The average per capita intake of both total and animal fat was also directly correlated with mortality from cancer of the pancreas (p less than 0.001). This suggests that animal sources of calories, protein, and fat may play an important role in the etiology of pancreatic cancer. PMID- 1751947 TI - Reproductive factors and cancers of the breast and genital organs--are the different cancer sites similarly affected? AB - Relationships between reproductive factors and cancer of the breast and genital organs were investigated in a prospective study of 63,090 Norwegian women. During followup from 1961 through 1980 1565 cases of breast cancer, 422 cases of cancer of the corpus uteri, and 471 cases of ovarian cancer were diagnosed. High parity was associated with low risk of cancer of the breast, corpus uteri, and ovary in analyses with adjustment for age at first birth. Age at first birth and age at last birth were positively associated with risk of breast cancer and inversely associated with endometrial cancer, whereas no clear associations were observed with ovarian cancer. Results suggest that the effect of a pregnancy on cancer risk is mediated, at least in part, by different mechanisms for these three sites. Age at menarche was inversely and age at menopause positively related to risk of breast and endometrial cancer, whereas no association was observed for ovarian cancer. In analyses of squamous cell carcinoma of the cervix uteri, an association with reproductive factors was expected from the known relationships with sexual habits. However, this cannot account for the high risk observed in this study in women with early age at first birth. PMID- 1751948 TI - First degree relatives of breast cancer patients: screening practices and provision of risk information. AB - Little is known about breast cancer screening knowledge and behaviors among women with a family history of breast cancer. Data gathered from 125 first-degree relatives of breast cancer patients indicated that only 63.3% of women over age 35 "ever" had a mammogram, 53% of women 40 or older reported a mammogram in the last year, and only 36.8% of all participants reported monthly breast self-exam (BSE). Self-reported BSE competence was generally poor. One hundred five (105) (84%) reported a clinical breast exam over the previous year. Only 71 (56.8%) of the women indicated that they had been asked about their family history of breast cancer by their physician, and minimal information about risk related to family history was provided. Worry about developing breast cancer was positively related to mammography use and BSE competence. Confidence in performing BSE and learning BSE from a physician/nurse were both positively related to competence. Women who believed they had control over finding breast cancer in its early stages reported more frequent BSE. Poor compliance of women with a family history of breast cancer in the practice of BSE and utilization of mammography, and lack of risk information provided by physicians mandate a search for effective intervention. PMID- 1751949 TI - Tumor necrosis factor-alpha and B-cell growth factor induce leukemic hairy cells to proliferate in vitro. AB - To clarify the mechanisms accounting for the hairy cell proliferation, in five patients with hairy cell leukemia (HCL), we evaluated the ability of neoplastic cells to proliferate in vitro in response to tumor necrosis factor-alpha (TNF alpha), B-cell growth factor (BCGF), and interleukin 4 (IL-4). In addition, supernatants recovered from cultures of unstimulated hairy cells were tested for the capability to induce the proliferation of allogeneic hairy cells. We demonstrated that TNF-alpha and BCGF were able to induce the in vitro growth of hairy cells (stimulation index (SI) ranging, at different concentrations, from 1.6 to 10.7 and from 1.6 to 25.1 for TNF-alpha and BCGF, respectively). IL-4 did not show any proliferative effect on hairy cells. When unstimulated hairy cell supernatants were tested for the proliferative activity on allogeneic hairy cells, we demonstrated a low proliferative effect that was not inhibited by an anti-TNF-alpha antibody. Our findings demonstrate that unstimulated hairy cells proliferate in vitro in response to TNF-alpha and BCGF, thus suggesting that these cytokines could be involved in an autocrine model of cell proliferation. PMID- 1751950 TI - Cell proliferation of human leukemia and solid tumors studied with in vivo bromodeoxyuridine and flow cytometry. AB - Bromodeoxyuridine (BUDR) is a thymidine analog that is incorporated into the DNA of proliferating cells. Because the dose of BUDR that is needed to label cells is not toxic, cell labeling can be accomplished in vivo by infusing the substance into patients. A monoclonal antibody against BUDR is then used to identify BUDR labeled cells. The same cell population can also be stained for DNA content with propidium iodide (PI). Using bivariate flow cytometry (FCM) for measurements, both the percentage of BUDR-labeled cells and their total DNA content can be evaluated. This technique allows one to obtain the labeling index (LI) and the DNA synthesis time (TS). The potential doubling time (Tpot) and the fractional turnover rate (FTR) can be mathematically derived. During a 15-month period, in vivo BUDR infusion to study cell kinetics was used in 112 consecutive patients with various types of malignant tumors: acute leukemia (50), gastric cancer (42), and brain gliomas (20). The procedure took 6 to 9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and in 80 (72%) of the 112 patients, respectively. Proliferative activity in 34 patients with acute nonlymphoblastic leukemias who were uniformly treated for remission induction and maintenance was measured from Tpot and FTR. It was greater in responsive than in nonresponsive patients, and in those who experienced remission for over 8 months than in those who had a shorter remission. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751951 TI - A proportionate mortality study on risk of bladder cancer among rubber workers. AB - A proportionate mortality study was based on a sample of 6208 workers who were employed for at least 4 months during the period from 1917 to 1983 in a rubber tire manufacturing plant in Ontario, Canada. Identifying information of the workers was extracted from company records and linked to the Ontario Cancer Registry 1964-1983 death files. Among the cohort, 153 cancer deaths (146 male, 7 female), which included 6 bladder cancer deaths (all male), were found. For the six bladder cancer deaths, average age at time of first employment was 33.5 years, and average time from first employment to time of death was 31.8 years (with a range from 25.3 to 38.3 years). Proportionate mortality ratio (PMR) and mortality odds ratio (MOR), and their standardized forms (SPMR and SMOR), were calculated using the general population in Ontario for comparison. PMR and MOR were found to be 1.44 and 1.45, respectively. When the Ontario proportionate cancer mortality was applied to the cohort, adjusted for age and sex, 4.69 bladder cancer deaths were expected. The six bladder cancer deaths among the rubber workers therefore represented a 1.28-fold increase in standardized proportionate bladder cancer mortality when compared to the general population. Age and sex adjusted SMOR was found to be 1.29. PMID- 1751952 TI - Large-scale production of human tumorcytotoxic macrophages grown from blood monocytes of cancer patients. AB - For adoptive immunotherapy protocols using cells of the macrophage (M phi) system, well differentiated and functionally competent effector cells are required. In this presentation the generation of a large number of M phi grown in vitro from blood monocytes (mo) is reported. Mononuclear cells (MNC) were collected by cytapheresis and subsequent Ficoll centrifugation. Mean yield was 6.9 x 10(9) MNC (range from 3 x 10(9) to 1.2 x 10(10), n = 18) with a mean mo count of 22 +/- 14%. MNC were cultured at 5 x 10(6)/ml in suspension on hydrophobic Teflon foils with 2% autologous serum for 7 days with recombinant human interferon-gamma (rhIFN-gamma) being present for the last 18 h of culture. Cells were harvested and activated mo-derived M phi separated from lymphocytes by counter-current centrifugal elutriation. On average, 42% of mo cultured could be recovered as M phi, the maximal number of M phi generated being 1.7 x 10(9) with a purity of up to 96%. Mo-derived M phi appeared to be mature by their expression of maturation-associated antigens and proved to be cytotoxic to allogeneic tumor targets in vitro. They secreted large quantities of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and granulocyte-macrophage colony stimulating factor (GM-CSF) upon stimulation with endotoxin. Using the technology described, this study revealed that large amounts of tumorcytotoxic M phi can be generated from the peripheral blood of cancer patients to be used in adoptive immunotherapy trials. PMID- 1751953 TI - A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes. AB - Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1751954 TI - [The noninvasive estimation of right atrial pressure improves the Doppler evaluation of the pulmonary systolic pressure]. AB - The right ventricular systolic pressure can be evaluated with the Doppler method through the right ventricular-atrial gradient (RV-RA gradient) and the right atrial pressure. The former is expressed by the transtricuspid velocity of flow, the latter is generally assumed. In 50 patients with elevated pulmonary pressure we tested whether ultrasounds may be utilized for the evaluation of the right atrial pressure, and whether the derived values contribute to improve the accuracy of the method. We estimated the right ventricular systolic pressure with method A: RV-RA gradient + 10; and method B: RV-RA gradient x 1.1 + 14, where 10 and 14 are the assumed right atrial pressure (mmHg). Through the collapsibility index of the inferior vena cava, taken as an ultrasound-derived index of right atrial pressure, we were able to identify 3 groups of patients with normal (Group 1, 14 cases), elevated (Group 2, 21 cases) and moderately elevated (Group 3, 15 cases) right atrial pressure, respectively. In them the right ventricular systolic pressures obtained with both method A and method B were compared to those derived with catheter. In Group 1 the non-invasive values were significantly closer to the invasive ones when calculated with method A; the same was true of method B in Group 2. In Group 3 the accuracy of the 2 methods was similar. We conclude that ultrasound assists in the non-invasive approximation of the right atrial pressure as well as in the choice of the appropriate formula, so that Doppler estimation of the right ventricular systolic pressure is improved. PMID- 1751955 TI - [Is lipid peroxidation responsible for the damage caused by postischemic reperfusion?]. AB - Peroxidation of membrane phospholipid polyunsaturated fatty acids is considered a major mechanism of the damage occurring during post-ischemic reperfusion. The evidences in support for this mechanism of damage are based on tissue malondialdehyde (MDA) quantitation by the thiobarbituric acid test (TBA-test). In an attempt to verify this topic we have subjected isolated and Langendorff perfused rabbit hearts to a period of 60 min of severe ischemia plus 30 min of reperfusion. At appropriate time points MDA was determined in the tissue by means of TBA-test and directly by reversed phase, high pressure, liquid chromatography (HPLC). We have found no correlation between the 2 compared assays. During reperfusion, there was the formation of non-lipid related, MDA like, TBA-reactive substance which leads to overestimation of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue MDA during ischemia and during the early phases of reperfusion. Our results demonstrate that TBA-test is not a reliable index of lipid peroxidation in organ systems and that MDA accumulation does not precede the evidence of the functional alterations occurring on reperfusion of the previously ischemic myocardium. These results are of relevance in the understanding of the exact mechanism of reperfusion damage as, in the same experimental model, oxy radicals have been shown to be generated and antioxidants are protective. PMID- 1751956 TI - [Is coronary angioplasty less costly than aortocoronary bypass?]. AB - We retrospectively compared the cost-benefit ratio of coronary bypass grafting (CABG) and percutaneous coronary angioplasty (PTCA). Data were obtained on 40 CABG's and 40 PTCA's patients treated from 15/2/86 to 15/9/86. All patients had at last 1-year follow-up. PTCA and CABG groups had similar baseline clinical and angiographic criteria. We analyzed the following cost components: real estate, biomedical products, drugs, hospital charges, medical fees, cardiac and non cardiac tests. Total cost of CABG exceeds that of PTCA by a factor of 1.64: 15,095,000 vs 9,201,346 Italian liras (ILit). Taking into account early and late medical and surgical complications, the factor decreases to 1.39: 15,746,500 vs 11,323,000 ILit. After 1 year of follow-up the factor decreases to 1.18: 16,613,500 vs 14,027,500 ILit. Our data show that the initial savings were reduced when complications and follow-up are considered, but PTCA's patients had shorter hospitalization, earlier return to work, lower psychosocial stress. PMID- 1751957 TI - Anomalous coronary arteries: a report of 2 cases of single coronary artery. AB - One patient with chronic exertional angina, not significant electrocardiographic signs of myocardial ischemia at exercise stress test and recent onset of angina at rest underwent coronary arteriography. A second one with known severe aortic stenosis underwent cardiac catheterization and coronary arteriography because of effort chest pain and syncope. A single coronary artery originating respectively from the right and from the left sinus of Valsalva but without significant coronary stenosis was detected in both patients. This entity is a quite uncommon finding of relevant interest if surgical treatment is required and good prognosis if not associated with additional cardiac anomalies. PMID- 1751958 TI - [The diagnosis by a Doppler color echocardiographic method of an aortocaval fistula following the rupture of an aortic aneurysm into the inferior vena cava]. AB - We describe a clinical case presenting 2 rare features. The first was a spontaneous aortocaval fistula which had developed from rupture of an atherosclerotic aortic aneurysm into the inferior vena cava. The second infrequent feature depended on the unusual method by which the diagnosis was performed. In fact, using an echo-color Doppler flow imaging (HP 77020A ultrasound system) with a 2.5 MHz echocardiographic probe abdominal examination showed an aneurysm of the descending aorta that communicated to a dilated inferior vena cava. Furthermore, flow study with color Doppler showed a continuous turbulent, mixed (arterial and venous) blood flow into the inferior vena cava. PMID- 1751959 TI - [The physiopathological mechanisms of transient regional myocardial ischemia and the approach to therapy]. PMID- 1751960 TI - [The intravascular imaging technic with ultrasound]. PMID- 1751961 TI - [The value of a tradition in the history of the Societa Italiana di Cardiologia]. PMID- 1751962 TI - Calcium-binding proteins in Aplysia neurons. AB - 1. Calcium (Ca)-binding proteins of neuronal ganglia and of single, identified neurons of the marine mollusk, Aplysia californica, were investigated. Using transblot/45Ca overlays two proteins, at Mr 45,000 and Mr 23,000, with a high Ca binding ability were found. 2. Western blot analysis revealed that the protein at Mr 45,000 could be separated by 2D-PAGE into proteins with Mr 40,000 and Mr 43,000. The protein at Mr 40,000 immunocross-reacted with antisera directed against parvalbumin and rat calbindin D-28K, indicating a novel Ca-binding protein sharing common antigenic determinants for both proteins. 3. The protein at Mr 23,000 could be separated into a group of proteins with Mr 13,000-20,000 which showed a high degree of similarity to sarcoplasmatic calcium-binding proteins (SCP). 4. We further investigated the protein pattern of single, identified neurons of different electrical activity (bursting, beating, and silent) by 2D-PAGE. Major differences were found in the range of low Mr and low pI, where Ca-binding proteins are generally located. A protein at high concentrations characteristic for silent cells migrated at a position similar to crayfish SCP. 5. The results show that various Ca-binding proteins are characteristic for neurons in the Aplysia nervous system and support the idea that they may effect the electrical behavior of nerve cells. PMID- 1751963 TI - Gamma-interferon, retinoic acid, and cytosine arabinoside induce neuroblastoma differentiation by different mechanisms. AB - 1. The effects of gamma-interferon (gamma-IFN), retinoic acid (RA), and cytosine arabinoside (ARA-C) on the growth, morphology, and phenotype of the human neuroblastoma (NB) cell lines, LAN-1 and GI-ME-N, have been extensively tested. 2. RA, gamma-IFN, and ARA-C induced a dose-dependent morphological differentiation and growth inhibition, without affecting cell viability. Cells exposed to 10(-6) M RA or 1000 U/ml gamma-IFN significantly decreased their growth rate within the first 24 and 48 hr of culture, respectively. Cells became smaller and polygonal and sprouted long cellular processes with varicosities along their courses. In contrast, ARA-C-differentiated cells were larger and flattened, with few elongated dendritic processes. 3. Analysis of membrane and cytoskeletal markers by immunofluorescence and Western blot showed several changes in NB-specific antigen expression after 5 days of treatment with all inducing agents. Analysis of labeled phosphatidylinositol metabolites from prelabeled cells showed, within 1 min of treatment with RA, a rapid decrease in inositol 1,4,5-trisphosphate and of 1,2-diacylglycerol levels. No changes in inositol phospholipid metabolism were observed in gamma-IFN- or ARA-C-treated cells. 4. We conclude that RA-induced decrease in phosphatidylinositol (PI) hydrolysis is not likely to be a consequence of the acquisition of a different phenotype, as its changes precede the acquisition of neuronal markers. In addition, gamma-IFN and ARA-C, both inducing a mature phenotype, did not affect PI hydrolysis. 5. Decreased PI hydrolysis seems to be sufficient, although not necessary, to commit NB cells to neuronal differentiation. Analysis of molecular mechanisms associated with NB cell differentiation may be helpful to clarify the potential of various biological agents in affecting the development of the neural cell. PMID- 1751964 TI - Relationship among methylation, isoprenylation, and GTP binding in 21- to 23-kDa proteins of neuroblastoma. AB - 1. Dimethylsulfoxide-induced differentiated neuroblastoma express high levels of membrane 21 to 23-kDa carboxyl methylated proteins. Relationships among methylation, isoprenylation, and GTP binding in these proteins were investigated. Protein carboxyl methylation, protein isoprenylation, and [alpha-32P]GTP binding were determined in the electrophoretically separated proteins of cells labeled with the methylation precursor [methyl-3H]methionine or with an isoprenoid precursor [3H]mevalonate. 2. A broad band of GTP-binding proteins, which overlaps with the methylated 21 to 23-kDa proteins, was detected in [alpha-32P]GTP blot overlay assays. This band of proteins was separated in two-dimensional gels into nine methylated proteins, of which four bound GTP. 3. The carboxyl-methylated 21 to 23-kDa proteins incorporated [3H]mevalonate metabolites with characteristics of protein isoprenylation. The label was not removed by organic solvents or destroyed by hydroxylamine. Incorporation of radioactivity from [3H]mevalonate was enhanced when endogenous levels of mevalonate were reduced by lovastatin, an inhibitor of mevalonate synthesis. Lovastatin blocked methylation of the 21 to 23 kDa proteins as well (greater than 70%). 4. Methylthioadenosine, a methylation inhibitor, inhibited methylation of these proteins (greater than 80%) but did not affect their labeling by [3H]mevalonate. The results suggest that methylation of the 21 to 23-kDa proteins depends on, and is subsequent to, isoprenylation. The sequence of events may be similar to that known in ras proteins, i.e., carboxyl methylation of a C-terminal cysteine that is isoprenylated. 5. Lovastatin reduced the level of small GTP-binding proteins in the membranes and increased GTP binding in the cytosol. Methylthioadensoine blocked methylation without affecting GTP binding. 6. Thus, isoprenylation appears to precede methylation and to be important for membrane association, while methylation is not required for GTP binding or membrane association. The role of methylation remains to be determined but might be related to specific interactions of the small GTP-binding proteins with other proteins. PMID- 1751965 TI - Inhibition of intracellular granule movement by microinjection of monoclonal antibodies against caldesmon. AB - Monoclonal antibodies, C2, C9, C18, and C21, against chicken gizzard caldesmon (called high molecular weight isoform) were shown to crossreact with a low molecular weight isoform of caldesmon in chicken embryo fibroblasts (CEF). These antibodies were used in a microinjection study to investigate the in vivo function of caldesmon in nonmuscle cell motility. Injected cells did not appear to change their morphology significantly; the cells displayed a flat appearance and were able to ruffle and locomote normally. However, in the C21 injected cells, saltatory movements of granules and organelles appeared to be greatly inhibited. This inhibition of granule movement was reversible, so that by 3 hr after injection, granules in injected cells had already recovered to normal speed. The inhibition of granule movement in cells injected with C2, C9, or C18 antibody, or with C21 antibody preabsorbed with caldesmon, were not significantly different from that in uninjected cells. In a previous epitope study, we demonstrated that, of the antibodies used in this study, only C21 antibody was able to compete with the binding of caldesmon to Ca++/calmodulin and to F-actin, although both C21 and C2 antibodies recognized the same carboxyl-terminal 10K fragment of gizzard caldesmon [Lin et al., 1991: Cell Motil. Cytoskeleton 20:95 108]. The caldesmon distribution in C21 injected cells changed from stress-fiber localization to a more diffuse appearance, when the injection was performed at 10 30 mg/ml of C21 antibody. We have previously shown that a monoclonal anti tropomyosin antibody exhibited motility-dependent recognition of an epitope, and that microinjection of this antibody specifically inhibited intracellular granule movements of CEF cells [Hegmann et al., 1989: J. Cell Biol. 109:1141-1152]. Therefore, it is likely that tropomyosin and caldesmon may both function in intracellular granule movement by regulating the contractile system in response to [Ca++] change inside nonmuscle cells. PMID- 1751966 TI - The identification of mammalian centrosomal antigens using human autoimmune anticentrosome antisera. AB - Human autoimmune sera were screened for the presence of anticentrosome autoantibodies. Two high titer sera were identified that reacted with HeLa, CHO, and PtK2 centrosomes by immunofluorescence, although the fluorescent patterns that were obtained using the two antisera were separate and distinct. Serum obtained from patient IJ contained antibodies that reacted with epitopes present only in mitotic centrosomes; staining of interphase centrosomes was never detected uing IJ antiserum. Immunoblot analysis demonstrated that antibodies present in IJ antiserum reacted with a 190 kD spindle pole antigen. Immunofluorescent staining of cultured mammalian cells demonstrated that antibodies present in serum obtained from patient SPJ reacted with both interphase and mitotic centrosomes. Characterization of SPJ antiserum by immunoblotting demonstrated that antibodies present in the SPJ serum recognized proteins of Mrs of 39, 185, and 220 kD, although the possibility that the 185 kD polypeptide was a proteolytic breakdown product of the 220 kD protein has not been eliminated. Neither antiserum was able to inhibit microtubule nucleation from centrosomes in a lysed cell system in which pure 6S tubulin was added to permeabilized cells following pretreatment of the cells with either SPJ or IJ antiserum. These antisera should be useful probes for studying the biochemistry of the mammalian centrosome. PMID- 1751967 TI - Analysis of inducible contractile rings suggests a role for protein kinase C in embryonic cytokinesis and wound healing. AB - A semi-in vitro system derived from Xenopus oocytes which allows induction of contractile ring (CR) formation and closure is described and exploited to elucidate regulatory and structural features of cytokinesis. The inducible CRs (ICRs) are composed of actin filaments and closure is actin filament-dependent as is cytokinesis in vivo. ICR closure in this system is calcium-dependent and pH sensitive, as is cytokinesis in permeabilized cells (Cande: Journal of Cell Biology 87:326, 1980). Closure of ICRs proceeds at a rate and with a kinetic pattern similar to embryonic cytokinesis. Collectively, these data demonstrate that this system is a faithful mimic of cytokinesis in vivo. ICR formation and closure is protein kinase C (PKC)-dependent and neomycin-sensitive, indicating that the PKC branch of the polyphosphoinositide pathway regulates formation of the actomyosin ring which is the effector of cytokinesis. Kinetic measurements show that the rate of ICR closure reaches a peak of 4-8 microns/sec. Since the maximum measured velocity of actin filament translocation by vertebrate, non muscle myosins is 0.04 micron/sec, the later observations support a model in which the CR is segmented, containing multiple sites where filaments overlap in a "sliding filament" fashion. Because the rate decreases after reaching a peak, the results also suggest that the number of overlap sites decrease with time. PMID- 1751968 TI - Post-translational incorporation of actin into myofibrils in vitro: evidence for isoform specificity. AB - The incorporation of actin into myofibrils has been examined in a cell-free system [Bouche et al.: Journal of Cell Biology 107:587-596, 1988; Goldfine et al.: Cellular and Molecular Biology of Muscle Development, 1989]. Actin was translated in a reticulocyte lysate in the presence of 35S-methionine (35S-actin) or purified from muscle and labeled with fluorescein-5-isothiocyanate (FITC actin). Myofibrils were incubated with either 35S-actin or FITC-actin and then analyzed by gel electrophoresis or fluorescence microscopy. When myofibrils were incubated with FITC-actin monomer in the reticulocyte lysate buffer, strong fluorescent labeling was observed in Z-band regions and less so in I-bands. No fluorescence was detected in non-overlap regions of A-bands. Confocal microscopic analysis of these myofibrils indicated that FITC-actin was distributed evenly across the diameter of the myofibrils. These observations suggest that actin incorporation in the reticulocyte lysate buffer occurred at sites in the sarcomere which contain actin. In contrast, FITC-actin showed a variety of non physiological incorporation patterns when incubated with myofibrils in the presence of an isotonic buffer (I-buffer). However, when ATP was added to I buffer, FITC-actin showed a pattern of incorporation into myofibrils similar to that seen in the reticulocyte lysate buffer. Immunoblots indicated that actin of native size was released from myofibrils during incubation in the reticulocyte lysate buffer. No actin release was detected when the myofibrils were incubated in I-buffer lacking ATP. We used this system to compare the incorporation of actin isoforms into myofibrils. Both alpha- and beta-actins exhibited incorporation into the myofibrils but there was a three-fold greater incorporation of the alpha isoform. We propose that the differential affinities of actin isoforms for myofibrils and other cytoskeletal structures could provide a mechanism for actin isoform targeting within the cytoplasm. PMID- 1751969 TI - Analysis of cDNA clones for Acanthamoeba profilin-I and profilin-II shows end to end homology with vertebrate profilins and a small family of profilin genes. AB - We have cloned and sequenced full length cDNAs for Acanthamoeba profilin-I and profilin-II. The genes and the encoded proteins are nearly identical except for the region between bp 121 and 210 where 35% of the nucleotides and 47% of amino acids differ. Most of these substitutions are conservative, although three of them are responsible for the differences in the isoelectric points of the isoforms [Kaiser et al., Cell Biol., 102:221-226, 1986]. The DNA sequence revealed six corrections in the previously published protein sequence of profilin I [Ampe et al., J. Biol. Chem. 260:834-840, 1985] and for the first time resolved the ambiguities at the five positions where profilin-IA and -IB differ. The DNA sequence of profilin-II also allowed us to make two corrections in the protein sequence [Ampe et al., FEBS Lett. 228:17-21, 1988a]. Probes prepared from the cDNAs revealed 1 profilin-IA gene, one strongly cross-hybridizing profilin-I gene and one strongly reacting profilin-II gene on Southern blots of Acanthamoeba DNA. Weaker reactions with other genomic DNA fragments leave open the possibility of one additional gene each for profilin-I and profilin-II. Four different profilin RNAs were resolved on Northern blots. It possible to align the sequences of the three Acanthamoeba profilins with the sequences of nine other profilins from five different phyla. There are only two invariant residues in these profilin sequences, but many pairwise identities and conservative substitutions that indicate considerable divergence of this family of proteins from its ancestral precursor. PMID- 1751970 TI - Dictyostelium discoideum essential myosin light chain: gene structure and characterization. AB - We have used a Dictyostelium essential myosin light chain (EMLC) cDNA clone to isolate additional cDNA clones which supply a different 3' sequence from that previously described. The revised cDNA sequence encodes a polypeptide of 150 amino acids. Amino acid residues 147-167 of the previously reported sequence are replaced by new residues 147 to 150. The new cDNA encodes a polypeptide with 66% amino acid sequence identity with the Physarum polycephalum EMLC, and approximately 30% identity with mammalian EMLC sequences. These new cDNA clones were used to isolate two genomic DNA fragments which contain the entire EMLC gene. The Dictyostelium EMLC gene contains a single intron located immediately 3' of the translation initiation codon and encodes a product most similar to MLC3 isoform of vertebrates. Primer extension analysis places the transcription initiation site approximately 90 nucleotides upstream of the translation initiation site. A DNA fragment containing 350 bases of sequence upstream of the putative transcription initiation site is sufficient to drive expression of a reporter gene upon reintroduction into growing Dictyostelium cells. In addition, the CAT reporter mRNA produced by this construct showed a pattern of developmental regulation similar to that previously reported for the endogenous EMLC mRNA. Based on comparison with published EMLC sequences from a variety of sources, the Dictyostelium EMLC shows slightly higher similarity to vertebrate EMLCs from striated muscle sources than nonmuscle sources. While Dictyostelium and human nonmuscle sequences display only 28% identity over their entire sequence, the region from residue 88 to 108 shows much higher identity (67%). The high evolutionary conservation of this region of the EMLC suggests it may play an important role in EMLC function, and as such, represents a good target for future mutagenesis studies. PMID- 1751971 TI - [Stiff man syndrome--an autoimmune disease]. PMID- 1751972 TI - [Initial clinical experience with the use of 31P MR spectroscopy in the examination of children with neuromuscular diseases]. AB - 31P MR spectroscopy (MRS) was used to investigate neuromuscular diseases of different origin in 35 patients, mostly children. After elaboration of the procedure of MR examination and evaluation of results the method of pattern recognition analysis was used. According to the results of 31P MR spectroscopy patients can be divided into three groups. Group A comprises patients with severe muscular lesions such as Duchenne dystrophy. The second group B is characterized by milder atrophic changes of muscle fibres. The third group comprises obscure cases. The 31P MRS method was also used for investigating the development of the disease in time--a drop of parameter PCR/Pi corresponds to a deterioration of the clinical condition of patients from group one. Maintenance of approximately the same values was observed in group B. An increase of PCR/Pi was also observed during administration of Prednisone in patients with child polymyositis. PMID- 1751973 TI - [Cystic meningiomas]. AB - The author gives an account of three cases of cystic meningioma in a group comprising 184 operated meningiomas (1.63%). He reviews views on the aetiology of the cystic peri- and intra-tumoural formation. Neuroradiological findings resembling glial and metastatic tumours with cystic or necrotic changes frequently lead to an incorrect preoperative diagnosis in this potentially curable lesion. For prevention of relapses of cystic meningioma it is essential to remove not only the solid tumourous node but the entire wall of the cyst, which may be difficult from the technical aspect. PMID- 1751974 TI - [Epilepsy and rehabilitation using psychological methods (psychotherapy)]. AB - 41 subjects (39 patients and two mothers) participated in 1983-1988 in group psychotherapy for ambulatory adult patients focused on psychosocial problems and questions of the therapeutic regime. According to the independent evaluation by the attending physician the individually outlined goal was achieved in 38% of the patients. 31% of the patients left without a special effect, however, participation in the group meant probably a certain enrichment of their life. Another 31% of the patients had a negative attitude to participation in the group. Successful patients attended much longer, had a significantly higher verbal IQ and all responded reliably in Washington's psychosocial seizure inventory--WPSI. Conversely, 27% of the other patients gave invalid responses to WPSI. Psychological procedures should be part of a wider scale of rehabilitation approaches to epilepsy, including occupational rehabilitation and club activities. PMID- 1751975 TI - [West's syndrome--infantile myoclonic spasms]. AB - The article is a review of contemporary knowledge of the so-called West syndrome. It deals with the definition, aetiology, clinical aspects, therapy and prognosis of this disease. In addition to the clinical picture of West's syndrome the author describes also recently described units which may fuse with this syndrome or mutually. The author deals on purpose in more detail with treatment of West's syndrome, in particular steroid administration (specially ACTH and its synthetic derivatives) as among our neurologists there are still very controversial views as regards indication and control of steroid treatment, sometimes associated with certain not always rational prejudices. PMID- 1751976 TI - [Present trends and use of ultrasonic diagnosis in neuroangiology and cerebrovascular diseases]. PMID- 1751977 TI - [International classification of headache (shortened form)]. PMID- 1751978 TI - HIV-1 infection among incarcerated men--Quebec. PMID- 1751979 TI - Tropical health and quarantine notes. PMID- 1751980 TI - [Power and helplessness in therapeutic care of children]. AB - The child is exposed to force, starting at birth, and force accompanies him through later life. Absence of force should thus start by gentle delivery in an operation theatre and be associated with the subsequent upbringing of the child. Trauma of separation in hospital is one of his most painful experiences. This led in the sixties to basic psychohygienic reforms in paediatric clinics, with unrestricted visiting times and admission of mothers to the department with the child. Force determines our lifestyle and penetrates via the mass media continuously into our families. Parents are therefore requested to alter their style of upbringing psychotherapists are requested to avoid any force used in aversive therapy by behavioural therapists or so-called "Festhaltetherapie" of autistic children. The number of disrupted families, demonstrated on the example of children of divorced parents indicates the tasks of "doctors as educators of children" (see Czerny). In an environment of soulles medicine based on apparatuses steady control of his activities are needed. The remedial teacher is an important assistant in paediatric hospitals. Psychological knowledge and experience can protect the doctor against abuse of force in therapy. PMID- 1751981 TI - [Current problems in pediatric ophthalmologic oncology]. AB - The authors give an account of contemporary problems of child ophthalmological oncology from the paediatrician's aspect. The most serious intraocular tumors are retinoblastomas, in the orbitopalpebral area rhabdomyosarcomas. The authors draw attention to the five main alarming symptoms typical for tumorous processes at these sites: red painful eye, leukokoria, acute visual failure, acute strabism and various rapidly developing protrusions of the bulbus. Subsequently they inform on possible ophthalmological complications of comprehensive oncological treatment. PMID- 1751982 TI - [Characteristics of E. coli strains isolated in infantile diarrhea]. AB - In a group of 50 strains of E. coli isolated from infants hospitalized on account of diarrhoea the authors investigated, based on the phenotypic manifestation and in a selected number of strains also genotypic factors of virulence: fimbrial adhesins, aerobactin, haemolysins, colicins, toxic and lethal action in mice, seroresistence and resistance against tetracycline, streptomycin, chloramphenicol, kanamycin, ampicillin and sulfamethoxidine. All strains had one to eight factors of virulence. The presence of plasmid DNA was confirmed in 14 of 16 tested strains. From this the authors conclude that the investigated virulence factors were in the majority coded plasmids. PMID- 1751983 TI - [What should the pediatrician know about retinopathy of prematurity?]. AB - The paper is concerned with the practical aspect of the problem of retinopathies of premature babies (ROP) from the aspect of collaboration of the child ophthalmologist and paediatrician. The paper provides basic information pertaining to contemporary possibilities of prevention and treatment of ROP, some late sequelae and their possible correction. The conclusions which ensure are the result of a confrontation of the author's experience and data in the literature. PMID- 1751984 TI - [Intermittent transcutaneous monitoring of acid-base equilibrium in neonates]. AB - The authors discuss intermittent transcutaneous monitoring of the acid base balance in blood where the feedback model: lungs-milieou interieur is used as part of a new theory, i.e. the concept of "electronic blood" (Kovac A.) which implies simulation of the internal environment by a computer. Part of the model, evidence of the existing relationship of the external and internal environment are the following parameters: a shift in the Haldane effect and the constant in Haldane's effect. The authors compare the values of the acid-base balance obtained by surgical means and by means of a computer. PMID- 1751985 TI - [Urethral dilation in the treatment of urinary tract infections in girls]. AB - In the presented retrospective study the authors evaluate the effect of dilatation of the urethra in the treatment of relapsing infections of the urinary pathways in girls. In 1982-1987 at the Clinic of Paediatric Surgery in Brno 387 girls with infections of the urinary pathways were examined, in 112 stenosis of the distal urethra was found, in 24 moreover vesicoureteral reflux and 40 suffered from enuresis. After dilatation of the urethra, the technique of which is described in detail the urinary findings were normal in 83% of the girls and in more than half significant or complete regression of the vesicoureteral reflux was noted, in more than two thirds enuresis was eliminated. The authors therefore recommend the method and also calibration of the urethra during examination of the patients. PMID- 1751986 TI - [Diaphragmatic hernia in the pediatric population in the Roznava District]. PMID- 1751987 TI - [Results of new research in the physiology of vision and its reflection in the care of younger patients with ophthalmic diseases]. PMID- 1751988 TI - [Report on the results of the SPTR P 12-335-802 DU 17 research tasks in the field of pediatrics]. PMID- 1751989 TI - [Infant mortality in Slovakia 1990--analysis and perspectives]. PMID- 1751990 TI - [Changes in children with mental retardation in a long-term study]. PMID- 1751991 TI - [Short report on mortality in children with a low birth weight]. PMID- 1751992 TI - [Pre-existing knowledge and knowledge gained from the print media about adoption and foster care by adoption seekers during the 2-3 year waiting period]. PMID- 1751993 TI - [Alkaline phosphatase activity in neutrophils in children with type I diabetes mellitus]. PMID- 1751994 TI - [Hemangiomatosis of the liver in a 3-month-old infant]. PMID- 1751995 TI - [Detection of T-lymphocytes using the E. coli strain ATCC 11303]. PMID- 1751996 TI - Postoperative myocardial damage in patients with coronary artery disease undergoing major non cardiac surgery. AB - A prospective study was carried out in a group of 50 patients with coronary artery disease, presenting for major non-cardiac surgery, to investigate the timing and incidence of further perioperative myocardial damage. A standardised anaesthetic was used. A standard 12-lead ECG was taken immediately before surgery and at 24, 48, and 72 hr after the start of anaesthesia. Blood samples were taken immediately preoperatively and at 6, 24, 48, and 72 hr after anaesthesia for total CK and CK-MB assay. Thirty-three patients (66%) showed ECG evidence suggestive of further infarction, and of these, two (4%) died in the immediate perioperative period. The first ECG change occurred in 27/31 (87%) by 24 hr, in 3/31 (10%) by 48 hr, and 1/31 (3%) by 72 hr. Twenty-nine patients (58%) including the two deaths showed CK-MB enzyme changes. The first elevation in CK-MB was nil at 6 hr and 72 hr, with 23/27 (85%) at 24 hr, and 4/27 (15%) at 48 hr. In 22/50 (44%) ECG and enzymes were correlative. Goldman and Cooperman risk indices were calculated for each patient. The Cooperman risk index was superior to the Goldman scale in the correlation of observed with predicted myocardial morbidity. Patients with ECG changes only before surgery were just as liable to further myocardial damage as those patients with ECG changes and a documented history of a previous infarct and/or symptoms. Myocardial damage is maximal in the first 24 hr after surgery, and may not be adequately predicted by current risk indices. PMID- 1751997 TI - Early postoperative myocardial morbidity in patients with coronary artery disease undergoing major non-cardiac surgery: correlation with perioperative ischaemia. AB - As a part of a study assessing early postoperative myocardial morbidity in 50 patients with active coronary artery disease undergoing major non-cardiac surgery, the ECG was monitored continuously for 24 hr after the onset of anaesthesia, using a frequency modulated (FM) Holter monitor. Concurrent automated blood pressure and pulse were measured non-invasively at three-minute intervals during anaesthesia and subsequently at five-minute intervals. Thirty patients were monitored with two-site ECG recordings, from modified V1 and V5 (Group A). Twenty patients had seventeen-site ECG monitoring, multiplexing a four by four array of precordial electrodes onto one channel of the frequency modulated recorder (Group B). Tapes were analyzed for noise, supraventricular and ventricular dysrythmias, runs of tachy- and bradycardia, and ST segment changes. These data were correlated with serial standard 12-lead ECGs and CK-MB assay in the 72 hr after surgery. Seven tapes from Group A could not be analyzed. Change (greater than 1 mm) on ST monitoring from both Groups A (14/23), B (14/20), correlated with serial 12-lead ECG and/or CK-MB changes. The majority of first ST change 19/28 (70%) occurred after anaesthesia. In 14/28 (50%) ST change occurred during episodes of tachycardia and elevated blood pressure (greater than 20% above baseline). Nine patients (9/23) in Group A had no ST change; however, six had serial 12-lead ECG and/or CK-MB changes. Six patients (6/20) in Group B had no ST changes, and none of these patients had any change of serial 12-lead ECGs or CK-MB assay. No patient complained of chest pain during the Holter monitoring period. Continual monitoring of heart rate and blood pressure and accurate ST monitoring are essential to detect and treat perioperative myocardial ischemia. A multiple-lead precordial system is substantially more sensitive than traditional two-lead ECG holter monitoring in detecting myocardial ischaemia. PMID- 1751998 TI - Metoclopramide does not decrease the incidence of nausea and vomiting after alfentanil for outpatient anaesthesia. AB - Sixty patients were studied in a randomized, double-blind manner to determine whether metoclopramide added to droperidol decreased further the incidence of emetic symptoms (nausea, retching, vomiting) in outpatients receiving alfentanil anaesthesia for nasal surgery. Group 1 (n = 30) received metoclopramide 0.15 mg.kg-1 and Group 2 (n = 30) received placebo. In addition, both groups received droperidol 0.02 mg.kg-1 immediately before anaesthesia which was supplemented by alfentanil 20 micrograms.kg-1 at induction followed by an infusion of 0.25-1 micrograms.kg-1.min-1. Emetic symptoms were assessed 0-3 hr, 3-6 hr and 6-24 hr after surgery. Both groups received similar doses of alfentanil (mean +/- SD; Group 1 4641 +/- 1894 micrograms, Group 2 4714 +/- 1640 micrograms). The percentage of patients who had either nausea or vomiting at 0-3, 3-6 or 6-24 hr was 23%, 14% and 13% in Group 1; and 20%, 17% and 10% in Group 2. The overall incidence for each group was 8/30 (27%). There was no difference in the incidence of emetic symptoms between the groups at any time interval or throughout the study. Metoclopramide did not improve upon the antiemesis of droperidol during alfentanil anaesthesia for outpatient nasal surgery. PMID- 1752000 TI - On-site risk management. PMID- 1751999 TI - Critical incidents in anaesthesia: medico-legal and other aspects. PMID- 1752001 TI - Why accidents happen. PMID- 1752002 TI - How to measure what happens. PMID- 1752003 TI - A systematic method for the investigation of anaesthetic incidents. PMID- 1752004 TI - Medico-legal consequences. PMID- 1752005 TI - Epinephrine-aminophylline-induced arrhythmias after midazolam or thiopentone in halothane-anaesthetized dogs. AB - The purpose of this study was to evaluate epinephrine-aminophylline-induced arrhythmias during halothane anaesthesia after induction with thiopentone or midazolam. Ten mongrel dogs were studied during 1 MAC halothane and 50% N2O:O2 anaesthesia while maintaining constant acid-base status. The minimal arrhythmogenic infusion rate of epinephrine (MAIRE) and the corresponding plasma concentration of epinephrine (MAPC) required to produce ventricular arrhythmias before and after aminophylline were higher following induction of anaesthesia with midazolam than with thiopentone (P less than 0.05); the MAIREs decreased stepwise with aminophylline (P less than 0.05). The correlation coefficient between individual MAIREs and MAPCs was 0.93 (P less than 0.001). Epinephrine alone and in combination with aminophylline was less arrhythmogenic after induction with midazolam than with thiopentone. PMID- 1752006 TI - Anaesthesia for Treacher Collins syndrome using a laryngeal mask airway. AB - Patients with Treacher Collins syndrome pose a serious problem to anaesthetists in maintaining their airway because of retrognathia. Two patients with Treacher Collins syndrome undergoing tympanoplasty are reported in whom a laryngeal mask was used in place of an endotracheal tube for airway maintenance. PMID- 1752007 TI - Anaesthetic management of Miller's syndrome. AB - Miller's syndrome is a rare congenital disorder with facial features similar to that of Treacher-Collins syndrome. This report details the anaesthetic management of an infant during multiple surgical procedures, beginning with pylormyotomy at one month of age. Airway management was difficult because of severe micrognathia and was accomplished using an awake intubation with a conventional straight blade modified for continuous administration of oxygen ("oxyscope"). Due to recurrent upper airway obstruction and the anticipated need for multiple surgical procedures in the first years of life, a tracheostomy was placed. Because of the multiple airway, orthopaedic, and nutritional difficulties, it is important that a prospective, multidisciplinary approach be used in these patients' care. Consideration should be given to early tracheostomy for airway maintenance. PMID- 1752008 TI - Role of two-dimensional transoesophageal echocardiography in the management of a right ventricular tumour. AB - Right ventricular outflow tract tumours are rarely reported. The perioperative management of a patient presenting for excision of an obstructing right ventricular outflow tract myxoma is described. Two-dimensional transoesophageal echocardiography was performed intraoperatively and was found to be of considerable value in understanding the pathophysiology of the tumour. Following excision of the tumour, right ventricular function improved and tricuspid regurgitation resolved. PMID- 1752009 TI - Clinical application of cardiac risk indices: how to avoid misleading numbers. AB - Perioperative cardiac complications are associated with a high mortality rate. During the preoperative assessment the anaesthetist must determine if the patient is at risk so that appropriate interventions can be made to ensure the best possible outcome. Over the past three decades several indices have been proposed to identify the surgical patient at risk of cardiac morbidity or mortality. These indices can be thought of as diagnostic tests which determine the likelihood of perioperative cardiac complication. In this article the authors review the epidemiological basis of diagnostic tests and apply this theory to three currently available indices of perioperative risk: the American Society of Anesthesiologists physical status classification, the Goldman multifactorial cardiac risk index and a modified version devised by Detsky. A case history describing a surgical patient with unstable angina is first presented to show how different indices can lead to different predictions. These indices are then analysed as if they were diagnostic tests to predict cardiac complications after surgery. The characteristics of diagnostic tests such as sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curves are described and applied to the indices. Basic principles such as odds ratio, likelihood ratio and their relation to prevalence and post test probability are also presented. This overview will help the anaesthetist to understand the limitations of risk indices as predictors of adverse cardiac outcome and to apply these scales more effectively to individual patients at different institutions. PMID- 1752010 TI - Successful use of a Fortec II vaporizer in the MRI suite: a case report with observations regarding magnetic field-induced vaporizer aberrancy. AB - Conducting a general anaesthetic within a magnetic resonance imaging (MRI) suite poses many problems for the anaesthetist. Ferromagnetic substances are contained in most anaesthetic and monitoring equipment. Their presence within the magnetic field may cause hazards and artifacts during imaging. This report describes the testing and use of a free-standing Fortec II vaporizer within an MRI suite. The Fortec II vaporizer's function was altered depending upon its distance from and orientation to the magnetic field. The MRI images were not affected by this vaporizer's presence within the MRI suite. We conclude that an inhalational anaesthetic can be administered, using a pretested free-standing anaesthetic vaporizer and a Bain circuit, within the magnetic field of a magnetic resonance imager. PMID- 1752011 TI - Flexible cystofibrescope for difficult intubation. PMID- 1752012 TI - Pharyngeal foreign body. PMID- 1752013 TI - Relationship between PaCO2-PETCO2 gradient and physiological dead space. PMID- 1752014 TI - Alarms in the operating room. PMID- 1752015 TI - Desflurane: the dawn of a new era? PMID- 1752016 TI - Perceived urgency and the anaesthetist: responses to common operating room monitor alarms. AB - Increasing numbers and varieties of electronic monitors are used in hospital operating rooms. Many of these are equipped with auditory alarms which are loud, insistent, or irritating, and thus are frequently disabled by the anaesthetist. This study was planned to evaluate two components of auditory alarm design which may influence the usefulness of the alarm: the perceived urgency of the auditory signal and its correlation with the urgency of the corresponding clinical situation. We also assessed the ability of practising anaesthetists to identify the monitor or condition responsible for the alarm. Sixty-four anaesthetists attending a national conference assessed ten common operating room alarm sounds for perceived urgency. Results were compared with the urgency of the corresponding clinical situation as determined by 12 senior anaesthetists. Discrepancies between the clinical and perceived urgencies of several monitor alarms were found, and there was no correlation between the two measures. The subjects were also tested for their ability to identify the alarm sounds correctly. The overall correct identification rate was 33%, and only two monitors were correctly identified by more than 50% of the subjects. The results of this study have implications for design and use of auditory alarms in hospitals and suggest the need for further research. PMID- 1752017 TI - Metabolism of desflurane and isoflurane to fluoride ion in surgical patients. AB - The metabolism of isoflurane and the investigational volatile anaesthetic desflurane to fluoride ion was examined in 25 surgical patients. The patients were randomly assigned to four groups, to receive isoflurane or desflurane at either 0.65 MAC or 1.25 MAC. Anaesthesia was induced in all patients with thiopentone and midazolam and included nitrous oxide 60% in addition to the volatile agent. Blood was drawn before induction and at the end of the operation for determination of serum fluoride ion concentration. Plasma fluoride ion concentrations increased (+ 1.36 +/- 0.93 microM, P less than 0.01) in patients receiving isoflurane but were unchanged (-0.13 +/- 0.50 microM) in patients receiving desflurane. Metabolic release of fluoride ion is less with desflurane than with isoflurane during administration of the anaesthetics to surgical patients, and is unlikely to be of clinical significance. PMID- 1752018 TI - Metabolic and endocrine responses to surgery during caudal analgesia in children. AB - Plasma concentrations of glucose, lactate, epinephrine, norepinephrine, insulin, cortisol and growth hormone were measured in 28 healthy children, three to six years of age, before, during, and after lower abdominal surgery. The children received premedication with secobarbital, 6 mg.kg-1, pentazocine, 0.5 mg.kg-1, and atropine, 0.01 mg.kg-1 im. Fourteen children received general anaesthesia with nitrous oxide and halothane, and 14 others received caudal analgesia with 1.5% mepivacaine. Plasma glucose, epinephrine and norepinephrine concentrations remained unchanged in the general anaesthesia group, but decreased during and after surgery in the caudal analgesia group (P less than 0.05). During surgery, these concentrations were different between the two groups (P less than 0.05). Plasma insulin and cortisol concentrations increased after surgery (P less than 0.05), and growth hormone concentration increased during and after surgery in the general anaesthesia group (P less than 0.05), but the concentrations of these hormones remained unchanged during and after surgery in the caudal analgesia group. Plasma lactate concentrations were unchanged in both groups. These results indicate that caudal analgesia suppresses the metabolic and endocrine responses to stress associated with lower abdominal surgery in children. PMID- 1752019 TI - Transcranial Doppler sonography: nitrous oxide and cerebral blood flow velocity in children. AB - To determine the effect of nitrous oxide (N2O) on cerebral blood flow velocity (CBFV) and cerebrovascular resistance index (RI+) in children, ten ASA physical status I or II patients aged one to eight years old, scheduled for urological procedures, were studied. Anaesthesia was induced with thiopentone 2 mg.kg-1, fentanyl 5 micrograms.kg-1 and diazepam 0.3 mg.kg-1. Muscular relaxation was ensured by using vecuronium 0.1 mg.kg-1. After tracheal intubation, anaesthesia was randomly assigned to either a mixture of air in oxygen (N2/O2) or 70% N2O in oxygen (N2O/O2) producing an FIO2 of 30%. Three sets of measurements of CBFV and RI+ were made with both gas mixtures. The CBFV and RI+ were measured in the middle cerebral artery (MCA) with a transcranial Doppler monitor. Measurements were made while using the initial gas mixture, then the second gas mixture was administered, and finally, the patient again was given the initial gas mixture. A continuous caudal epidural or lumbar epidural block was performed before skin incision. Neuromuscular blockade was maintained with vecuronium 0.05 mg.kg-1. Temperature, heart rate, end-tidal CO2, arterial oxygen saturation, haematocrit and arterial blood pressure were maintained constant. Ventilation was adjusted to achieve normocapnia. The CBFV increased when 70% N2/O2 was replaced by 70% N2O/O2 (P less than 0.05) while the CBFV decreased when 70% N2/O2 was readministered (P less than 0.05). Likewise, the CBFV decreased when 70% N2O/O2 was replaced by 70% N2/O2 (P less than 0.05) while the CBFV increased when 70% N2O/O2 was readministered (P less than 0.05). PMID- 1752020 TI - Alfentanil infusion for sedation in infants and small children during cardiac catheterization. AB - We have analyzed several sedation techniques for paediatric cardiac catheterization which offer stable conditions for a few hours investigation, and maintain spontaneous breathing. In the present study, after premedication with oral flunitrazepam 0.1 mg.kg-1, 14 children aged 1-17 mo were sedated with an individually titrated alfentanil infusion. Every patient was sedated to a level which produced no reaction to pain or any discomfort. The induction dose and the maintenance requirement of alfentanil were 24 +/- 8 micrograms.kg-1 and 32 +/- 8 micrograms.kg-1.hr-1 (mean +/- SD), respectively. These doses were less in cyanotic than in acyanotic patients: 21 +/- 6 vs 28 +/- 8 micrograms.kg-1 and 29 +/- 10 vs 34 +/- 3 micrograms.kg-1.hr-1, respectively (P less than 0.05). The mean plasma concentration of alfentanil during maintenance of sedation was 79 +/- 23 ng.ml-1. Ventilation of two children was assisted for a short time after an incremental bolus of alfentanil. It is concluded that an alfentanil infusion technique with close monitoring of breathing is a practical sedation method for paediatric cardiac catheterization. PMID- 1752021 TI - Evaluation of oxygen saturation monitoring by pulse oximetry in neonates in the delivery system. AB - The pulse oximeter was evaluated for use in neonates in the delivery room. One hundred neonates, delivered vaginally or by Caesarean section with general or epidural anaesthesia, were studied. After delivery, pulse oximetry probes were placed simultaneously on the ulnar side of the right hand and on the right Achilles tendon to determine whether there was a difference in arterial oxygenation (SpO2). Measurements of SpO2 were taken at 1, 5, 10 min, and 24 hr after delivery. At one and five minutes, SpO2 recorded from the right hand was higher than that recorded from the lower extremities (71.9% +/- 6.5% vs 63.4% +/- 4.3% and 83.3% +/- 4.2% vs 76% +/- 4.1%, mean +/- SD, respectively). At ten minutes these differences diminished, and had almost completely disappeared after 24 hr. These results can be explained by the presence of R-L shunting at the ductus arteriosus level, producing reduced SaO2 in the lower extremities. Oxygen saturation did not differ between neonates delivered vaginally or by Caesarean section, regardless of the presence or type of anaesthesia. We concluded that neonates remain relatively desaturated in the immediate postpartum period and that the SpO2 obtained from the right hand is a better index of neonatal oxygenation than that obtained from the heel. PMID- 1752022 TI - Large tidal volume ventilation improves pulmonary gas exchange during lower abdominal surgery in Trendelenburg's position. AB - Impaired pulmonary gas exchange is a common complication of general anaesthesia. Periodic hyperinflation of the lungs and large tidal volume ventilation were the first preventive measures to be widely embraced, but their effectiveness in clinical practice has never been clearly established by controlled clinical studies. To assess their effects in high-risk patients we studied 24 adults having lower abdominal gynaecological surgery in the Trendelenburg (head down) position. Pulmonary oxygen exchange was determined during four steady-states: awake control (AC), after 30 min of conventional tidal volume (CVT, 7.5 ml.kg-1) or high tidal volume (HVT, 12.7 ml.kg-1) ventilation, introduced in random order, and five minutes after manual hyperinflations (HI) of the lungs. The patients' lungs were ventilated with air/O2 by an Ohmeda volume-controlled ventilator via a circle system. The FIO2 was controlled at 0.5, and FETCO2 was controlled by adding dead space during HVT. Arterial blood gas analysis was used to calculate the oxygen tension-based indices of gas exchange. There was significant deterioration of (A-a)DO2 at 30 min in Group A, whose lungs were first ventilated with CVT (81.6 +/- 7.2 to 166.8 +/- 13.7 mmHg, P less than 0.001); but not in Group B, whose lungs were first ventilated with HVT (77.0 +/- 9.9 to 104.4 +/- 16.8 mmHg). When Group A and B data were pooled there was no difference between randomized CVT and HVT, but improvement occurred after HI. In this model of compromised O2 exchange large inflation volumes (HVT and HI) were of considerable clinical benefit, HVT prevented and HI reversed the gas exchange disorder. PMID- 1752023 TI - Effects of rGM-CSF on leukemia cell proliferation and on the incorporation of cytosine arabinoside into DNA. AB - In vitro studies of the effects of recombinant granulocyte macrophage-colony stimulating factor (rGM-CSF) on freshly obtained human leukemia cells were conducted to determine if there is a relationship between the effects of this growth factor on the proliferative characteristics of leukemia cells and on their incorporation of cytosine arabinoside (araC) into DNA. While rGM-CSF was found to be able to stimulate both leukemia cell proliferation and araC incorporation, for individual leukemia specimens there was no consistent relationship among these effects. In some specimens proliferation was stimulated without an increase in araC incorporation. The reverse was also observed. These studies demonstrate the difficulty in identifying assays capable of predicting the clinical effects of growth factors on leukemia cells in patients since the effect in vitro vary with the assay. PMID- 1752024 TI - Mitochondrial nucleotide translocase from skeletal muscle of halothane sensitive pigs: an electrophoretic study. AB - ATP translocation into mitochondria isolated from halothane-sensitive pig (HP) muscle was dramatically reduced compared with normal pigs (NP). To determine if this was due to a decreased amount of ATP translocase in the mitochondrial membranes, or a structural modification of this protein, an electrophoretic study was undertaken. Total proteins and purified translocase preparations from (NP) and (HP) mitochondria were analyzed by SDS gel electrophoresis. In the two types of mitochondria no significant differences were observed either in the amount of ATP translocase or in the molecular weight. Also, neither nonequilibrium pH gradient gel electrophoresis nor the analysis of peptides produced by limited proteolysis revealed any structural difference between the two types of protein. On the basis of these results, the depressed translocase activity observed in (HP) mitochondria cannot be explained by a reduced amount of the nucleotide translocase, nor a structural alteration of this protein. Possible inhibition of (HP) translocase activity by Ca2+ accumulation or by other mechanisms is discussed. PMID- 1752025 TI - A comparative study of the effects of the diamine oxidase inhibitor aminoguanidine, with or without dietary restriction, on the nucleic acid and protein composition of cardiac and type I and type II skeletal muscles of the rat. AB - It has been proposed that the diamine oxidase inhibitor aminoguanidine may be a potential therapeutically important anabolic agent. An investigation was therefore made into the effects of aminoguanidine treatment with or without nutritional restriction, on cardiac and skeletal muscles containing mainly of either Type I (i.e. soleus) or Type II fibres (i.e. plantaris) or a mixture of Type I and II fibres (i.e. gastrocnemius). After 3 weeks, dietary restrictions reduced cardiac weight, protein, RNA and DNA contents by between 31 per cent and 36 per cent. Similar, but smaller, reductions were observed in the soleus (18-31 per cent), plantaris (22-34 per cent) and gastrocnemius (22-34 per cent). Aminoguanidine had no effect on the heart of the rats fed ad libitum, nor did it alter the response to dietary restriction. Treatment with aminoguanidine had no overt anabolic effect on skeletal muscle, but a reduction in DNA content was observed. It was concluded that cardiac protein and nucleic acid contents are more sensitive to dietary deprivation than either anaerobic or aerobic skeletal muscles. Furthermore, aminoguanidine does not appear to promote growth or reduce catabolism as previous studies have suggested. PMID- 1752026 TI - Variation in the isoenzymes of N-acetyl-beta-D-glucosaminidase and protein excretion in aminoglycoside nephrotoxicity in the rat. AB - Three aminoglycosidic antibiotics: tobramycin, amikacin and sisomicin were administered to rats. There was an increase in the activity of N-acetyl-beta-D glucosaminidase (NAG) excreted in the urine and this was characterized by a change in the isoenzyme profiles eluted from DEAE--cellulose. The largest increase in NAG activity was observed following sisomicin administration due mainly to an increase in the B-form of NAG with a concomitant fall in the intermediate (I-form). Separation of urinary proteins by SDS-polyacrylamide gel electrophoresis demonstrated a mixed tubular and glomerular proteinuria following administration of sisomicin. It is concluded that the separation of NAG isoenzymes and urinary proteins provides valuable additional information on the nature and severity of antibiotic nephrotoxicity. PMID- 1752027 TI - Managing three common oncologic emergencies. PMID- 1752028 TI - Lytic lesion of the knee in a 27-year-old man. PMID- 1752029 TI - Pulmonary hypertension secondary to fibrosing mediastinitis. PMID- 1752030 TI - Severity of illness: APACHE II analysis of an ICU population. AB - We reviewed the population of a surgical intensive care unit from July 1, 1987 to June 30, 1988, adjusting for severity of illness using the APACHE II system. Nineteen different departments admitted a total of 613 patients to the surgical intensive care unit. Predicted mortality was 22.9%; actual mortality was 15.7%. APACHE II generated reports which included analysis by age, mortality risk, department, primary physician, and diagnosis. We recommend reporting intensive care unit outcome by APACHE criteria to allow more meaningful comparisons of data and standardization of quality assurance programs. Finally, we present a critical review of the current APACHE II system and describe developments to be included in APACHE III. PMID- 1752031 TI - Demographics of long-term ventilator-dependent patients outside the intensive care unit. AB - Continued management of clinically stable ventilator-dependent patients in the intensive care unit is controversial, given the expense and limitations of intensive care resources. A proposed alternative, which could reduce the cost of care, has been "noninvasive respiratory units." We review the management of 99 ventilator-dependent patients on routine nursing floors to define our case mix and the outcome of long-term care. PMID- 1752032 TI - Signal-averaged electrocardiography for detection of ventricular tachycardia using fast Fourier transform filtering on a standard ECG cart. AB - Signal-averaged electrocardiography has been advocated as a technique to predict the occurrence of ventricular tachycardia, especially in patients with ischemic heart disease. We studied a heterogeneous population of 77 patients referred for electrophysiologic testing using a recently developed fast Fourier transform filtering system available as part of a standard electrocardiography cart. The sensitivity, specificity, and positive predictive accuracy of this system were consistent with those previously determined using bidirectional Butterworth filters or finite impulse response filtering techniques. This new filtering approach in generation of signal-averaged ECG data for detection of ventricular tachycardia has promise but will require use in larger groups to establish its true clinical value. PMID- 1752033 TI - Perioperative blood transfusion and survival of breast cancer patients after modified radical mastectomy. AB - To investigate the effect of perioperative blood transfusion on the survival of patients with breast cancer, the authors reviewed the clinical records of 455 patients who underwent modified radical mastectomy between 1960 and 1979. Thirty eight patients (8.4%) received blood transfusions. For stage I patients who received perioperative transfusions, 5- and 10-year survival rates were 53% and 47%; for the no-transfusion group, the rates were 93% and 85%. There was also a significant difference in disease-free survival for stage I patients: for the transfusion group, 5- and 10-year survival rates were 47%; for the group not receiving a transfusion, the rates were 89% and 84%. For stage II patients, there was no difference in total or disease-free survival between those who received transfusions and those who did not, and both groups had comparable distribution of nodes. PMID- 1752034 TI - Experimental limbic epilepsy: models, pathophysiologic concepts, and clinical relevance. AB - Complex partial seizures originating in the temporal lobe are one of the most common types of seizures in patients with epilepsy. They are frequently intractable to medical treatment and are increasingly considered for surgical therapy. These seizures are often associated with focal epileptogenicity in limbic structures (amygdala and hippocampus) or with rapid spread of seizure activity to these areas. Much research is being undertaken to better understand this disorder and to develop more effective approaches to diagnosis and treatment. Experimental work in animals has contributed to the understanding of epileptogenesis, the interictal state, and the homeostatic mechanisms that limit seizure activity. PMID- 1752035 TI - Orf: case report and literature review. AB - Ecthyma contagiosum, or orf, is an uncommon dermatosis resulting from cutaneous infection with sheep pox virus. It is generally a benign and self-limited condition. Early clinical recognition is paramount to avoid unnecessary surgical intervention or extensive diagnostic workup. Diagnosis is usually based on a clinically typical skin lesion, characteristic histology, and a history of sheep exposure. We report the case of an infected sheep farmer and review the literature. PMID- 1752036 TI - Benefits and risks of blood transfusion. PMID- 1752037 TI - Caring for the hospitalized ventilator-dependent patient outside the ICU: united and stand, or divided and fall? PMID- 1752038 TI - Cryopreservation and transplantation of immature rat retina into adult rat retina. AB - A bank of freeze-stored donor retinas would free transplantation research from dependence on availability of fresh donor tissue. Donor retinas from E13, E16, E19 and E22 (P1) rat embryos were cryoprotected and stored in liquid nitrogen for up to 8 months. Cryopreserved and fresh donor retinas were grafted to adult rat retina. After 4 weeks survival, transplants were evaluated according to a scoring protocol for the criteria of size, viability, lamination and integration. All donor ages of fresh and cryopreserved retina resulted in successful transplants, with the exception of cryopreserved E13. Cryopreserved grafts were significantly less laminated than grafts of fresh tissue. The best lamination scores of cryopreserved transplants were achieved with donor age E16. Surviving transplants were found in the epiretinal and/or subretinal space. Subretinal transplants had higher viability scores than did epiretinal grafts; the difference was more pronounced with transplants of cryopreserved than with fresh tissue. Fresh subretinal transplants were also significantly better laminated than fresh epiretinal transplants. This study shows that (1) cryopreserved retinal donor tissue can successfully be transplanted to rat retina; and (2) the subretinal space appears to be more favorable than the epiretinal space for retinal transplants. PMID- 1752039 TI - Muscle-derived factors reverse the cholinotoxic effects of ethanol during early neuroembryogenesis in the chick embryo. AB - The interaction between muscle-derived factors and ethanol on cholinergic neuronal expression was studied in the chick embryo during early neuroembryogenesis using choline acetyltransferase (ChAT) as cholinergic neuronal marker. Ethanol (10 mg/50 microliters) and limb muscle extract (130 micrograms protein/50 microliters) (LME) were administered in ovo either alone or concomitantly at embryonic days 1-3 (E1-E3); or ethanol was given E1-E3 and followed by LME at E4-E7. All groups were sacrificed at embryonic day 8 (E8) and ChAT activity was assayed in homogenates of whole brain and of spinal cord. As previously reported, ethanol at E1-3 produced a 30% decrease in brain ChAT activity and 35% in spinal cord. Concomitant administration of ethanol and LME at embryonic days E1-E3 eliminated the decrease in choline acetyltransferase activity produced by ethanol in the brain, but not in the spinal cord. On the other hand, administration of LME at embryonic days E4-E7 to embryos pretreated with ethanol at embryonic days E1-E3, raised ChAT activity to control level in the spinal cord, but only partially restored ChAT activity in the brain. In view of the alleged neurotrophic effects of muscle-derived factors on neuronal survival and neuronal growth, we interpret these findings to suggest that LME in addition to its ability to decrease natural neuronal death, may prevent death resulting from neurotoxicity. PMID- 1752040 TI - Stereological analysis of the hypothalamic ventromedial nucleus. II. Hormone induced changes in the synaptogenic pattern. AB - Stereological electron microscopic analysis of the rat hypothalamic ventromedial nucleus (VMN) throughout postnatal development revealed that synaptogenesis takes place up to day 45. Our results disclosed a sexual dimorphism in the synaptic organization of the neuropil of the ventrolateral (VL) subdivision of the VMN. The numerical densities of spine and shaft synapses in the adult male were higher than in the female. A dimorphic pattern in the numerical density of spine synapses occurred as early as day 5, and was present throughout postnatal life, even though in the adult rats both spine and shaft synapses were sexually dimorphic. Neonatal treatment of female rats with testosterone increased the numerical density of axodendritic synapses, inducing a pattern similar to the adult male. On the other hand, administration of tamoxifen to newborn male rats significantly reduced the numerical density of spine synapses to levels comparable to normal female rats. PMID- 1752041 TI - Development of rostrocaudal dendritic bundles in rat thoracic spinal cord: analysis of cholinergic sympathetic preganglionic neurons. AB - Using monoclonal antibodies to choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP), we have analyzed the development of the dendritic bundles formed by cholinergic sympathetic preganglionic neurons (SPNs) in relationship to changes in the organization of glial fibers. In adult rat thoracic spinal cord, SPNs in the intermediolateral (IML) and central autonomic (CA) regions extend dendrites in both the mediolateral and rostrocaudal directions, forming a ladder-like pattern in horizontal sections of thoracic spinal cord. We report that, while the mediolateral dendrites form prenatally, the rostrocaudal dendritic bundles are not detected until at least a week later, during early postnatal life. The rostrocaudal dendrites develop rapidly during the first postnatal week, and achieve an adult-like pattern by postnatal day 14. The observed ontogenetic arrangements of dendritic bundles were correlated with the developing organization of astroglial processes with which they are intimately associated. While the appearance of mediolateral dendrites is consistent with the radial organization of glial in the embryonic spinal cord, the developmental time course of the rostrocaudal dendritic bundles coincides with the transformation of glial cells from this predominantly radial or transverse orientation to the randomly-oriented, stellate pattern of mature astrocytes. This temporal association suggests that ontogenetic changes in the organization of glial cells may contribute to the differential development of mediolateral and rostrocaudal dendritic patterns in the spinal cord. PMID- 1752042 TI - Maturational and aging effects on guanine nucleotide binding protein immunoreactivity in human brain. AB - Age-related changes in transmembrane signal transduction have been reported for a number of hormonal receptors in human tissues. Guanine nucleotide binding proteins (G-proteins) are major regulatory components in the signal transduction processes for numerous receptors. Developmental changes in the abundance of specific G-protein alpha subunits, especially for Go, have already been shown in rat brain and in neuronal cell lines. In this study, immunoblotting analyses were performed with specific rabbit polyclonal antisera to Gs alpha, Gi alpha, Go alpha, and G beta subunits to estimate semi-quantitatively these G-protein subunits in samples of parietal cortex obtained postmortem from 18 subjects free of neurologic or psychiatric disease whose ages ranged from 3 days to 92 years. The Gs and Gi alpha subunit immunoreactivities were correlated significantly and inversely with age. The Gi alpha immunoreactivity declined markedly (46%) after the age of 40. As other G-protein subunit concentrations showed no age-dependent changes, the observed relationship between Gs and Gi alpha subunits and age is not likely due to cell loss occurring with advancing age. Of particular interest, the ratio of 52 to 45 kDa Gs alpha subunit immunoreactivities was significantly higher in infants than that found for adult parietal cortex. Given that changes in G-protein subunit abundance directly affect receptor-G-protein-effector functionality and response, these age-related alterations may be of importance in cerebral dysfunction and the development of neuropsychiatric disease in the later years of life. PMID- 1752043 TI - The histopathological, behavioral and neurochemical effects of intraventricular injection of ethylcholine mustard aziridinium (AF64A) in the neonatal rat. AB - This study investigated the histopathological, behavioral and neurochemical effects of bilateral injection of 2.0, 0.5 and 0.1 nmol/ventricle ethylcholine aziridinium (AF64A) on postnatal day (PND) 2. The rats showed a significant, but non-dose-related reduction of choline acetyltransferase (ChAT) in the hippocampus but not the cerebral cortex or the caudate nucleus when sacrificed on PND 16. No effect on ChAT was found in any region at PND 58. The group given 2 nmol/ventricle were hyperactive and showed a deficit in spatial learning when tested on the Morris water maze at PND 38-43. No such differences were observed for the rats injected with 0.1 or 0.5 nmol/ventricle AF64A. This spatial learning impairment in the 2 nmol group was associated with non-specific tissue damage seen only in animals from this group that were sacrificed at PND 40. This tissue damage was most evident in the left medial frontal cortex, the caudate nuclei and the anterior dorsal hippocampus. PMID- 1752044 TI - Molecules secreted from target and non-target tissues promote and repel sympathetic fiber distribution in vitro. AB - By using an in vitro assay system detecting the ability of nerve terminals to recognize the test molecules, I found that sympathetic fibers distributed densely on substrates coated with the particulate (adheron) fractions of growth conditioned medium from expansor secundariorum (target tissue), but did not on substrates coated with those from skeletal muscle (non-target). This result suggests that adheron particles are involved in the haptotactic process of specific sympathetic innervation on the target tissue. PMID- 1752045 TI - Role of fibronectin in the inhibitory effect of TGF-beta on choline acetyltransferase activity in co-cultures of spinal cord neurons and myotubes. AB - We have recently shown that the enhanced expression of choline acetyltransferase (ChAT) activity in co-cultures of spinal cord motoneurons and muscle cells was blocked by transforming growth factor-beta (TGF-beta) (Dev. Brain Res., 57, 129 137, 1990). This study was performed to investigate the role of fibronectin in this effect. TGF-beta increased fibronectin level about 2-fold in extracellular matrix of spinal cord cells and skeletal myotubes in culture. Addition of a synthetic polypeptide that competitively inhibits fibronectin binding to its cell surface receptor recovered the TGF-beta-induced suppression of ChAT activity in co-cultures. The polypeptide did not affect ChAT activity in cultures of spinal cord cells alone or in co-cultures without TGF-beta. These results indicate that TGF-beta inhibits the stimulation of ChAT activity in spinal cord neurons in co culture through a change in the composition and/or amount of fibronectin in the extracellular matrix at neuromuscular contacts. PMID- 1752047 TI - Distribution of immunoreactive relaxin in the genital tract and in the mammary gland of non-pregnant women. AB - Relaxin was determined in healthy and pathological tissue samples from mammary gland, ovary, myometrium and cervix uteri of non-pregnant women. Relaxin could be detected in all groups of tissues examined. The highest values were found in healthy ovary, the lowest concentrations in the cervix, which is known as a target organ for relaxin activity during pregnancy. Mammary parenchyma showed the highest specific activity of all healthy tissues examined. The relaxin concentration in myoma tissue is significantly higher than in healthy myometrium. PMID- 1752046 TI - Effects of early in ovo administration of ethanol on expression of the GABAergic neuronal phenotype in the chick embryo. AB - In order to study the influence of ethanol on GABAergic neuronal expression in the chick embryonic brain, activity of glutamate decarboxylase (GAD; a GABAergic neuronal marker) was examined in whole brain derived from embryonic chick following the in ovo administration of ethanol. GAD activity was already detectable by 3 days of embryogenesis and exhibited a logarithmic increase up to embryonic day 16 (E16). By E18, GAD activity began to plateau. Administration of ethanol (10 mg/50 microliters/day) to embryos in ovo on days E1-E3, resulted in increased GAD activity in whole brain when embryos were sacrificed at E8. However, when embryos were administered ethanol on days E4-E7, activity of GAD was unchanged as compared with controls. Similarly, when embryos were administered ethanol chronically from E1-E7 no significant effect was observed in GAD activity. The increase observed in GAD activity after exposure to ethanol during a period of active neuronal proliferation (E1-E3) supports our view that E1-E3 is the critical period of sensitivity to ethanol with respect to the development of neuronal phenotypes during embryogenesis. Furthermore, the absence of any significant effect of ethanol administered from E1 to E7 on GAD activity suggests the existence of a compensatory response to ethanol insult. PMID- 1752048 TI - Intra-uterine foetal death: an avoidable diagnostic pitfall. AB - A case is presented where maternal tachycardia was misinterpreted as foetal heart activity on cardiography in a case of IUFD. Diagnostic implications and the use of real line ultrasound scanning are discussed. PMID- 1752049 TI - Psychological aspects of therapeutic abortion after early prenatal diagnosis. AB - The early discovery of a fetal pathology creates a "crisis" situation fraught with psychic problems for the couple who must live through it. The Authors observed a group of patients in the second trimester of pregnancy. They had all requested therapeutic abortion since serious malformation of the fetus had been confirmed. By means of a questionnaire constructed for the purpose, certain characteristics of fetal malformation and of pregnancy were evidenced, as well as the way these were experienced by the patients. The immediate and delayed reactions to the diagnosis of malformation were also studied, as was the experience lived when faced with the choice of abortion. PMID- 1752050 TI - Peritoneal fluid volume parameters in infertile patients. AB - The peritoneal fluid volume (PFV) and its cellular and acellular components have been repeatedly associated with infertility. The PFV from 88 infertile women was analyzed in relation to endometriosis, pelvic adhesions, tubal patency, luteinization, endometrial cells and macrophages. The independent existence of parameters such as the onset of luteinization, the increased population of macrophages and the presence of endometriosis increase statistically significantly the PFV. In the presence of peritoneal adhesions or/and obstructed tubes the PFV was significantly decreased. PMID- 1752051 TI - Evaluation by means of radius bone densitometry of the fracture risk due to osteoporosis in post-menopause. AB - The aim of this work is to establish the predictive value of radius bone density with reference to the risk of fracture in postmenopausal women. Our data confirm a significant predictability of the radius for limb and rib fractures, but not for vertebral bones. PMID- 1752052 TI - Telephonic transmission of cardiotocographic recordings from a remote facility to an obstetric unit. AB - The Authors describe their experience in telephonic transmission of cardiotocographic recordings. With a Corometrics 116 and 410 unit installed in a remote facility, 61 CTG recordings were tele-transmitted and received by a Toshiba personal computer. The concordance between original and transmitted CTG record was excellent and a very low percentage of signal loss during transmission (3.2%) was found. The advantages of telephone transmission of CTG in peripheral areas are stressed. PMID- 1752053 TI - Induction of labour in the presence of ruptured membranes with prostaglandin E2 gel. AB - The study shows the safety and the efficacy of labour induction with prostaglandin E2 gel. By combining an initially conservative approach with later induction by PGE2 a vaginal delivery rate of 96.8% was achieved. PMID- 1752054 TI - Maternal serum cortisol and prolactin variations during labor. AB - Maternal serum cortisol (F) and prolactin (PRL) levels were measured during labor in 20 uncomplicated pregnancies. Four pregnant women were admitted with ruptured membranes (RM group) and 16 were admitted with intact membranes (IM group), ten with spontaneous onset of labor (SL group) and 10 with induced labor (IL group), five with a prolonged for duration labor (PL group) and 15 with a normal for duration labor (NL group). Before the inset of labor F levels were statistically higher (p less than 0.05) in the RM group (x = 975 ng/ml), than in the IM group (x = 664 ng/ml), and also in the SL group (x = 783 ng/ml), than in the IL group (x = 679 ng/ml). During labor, in all twenty pregnant women a marked rise of F (from x = 726 ng/ml before the onset of labor, to x = 911 ng/ml) and a marked fall of PRL (from x = 161 ng/ml to x = 122 ng/ml) were observed (p less than 0.05). In the PL group the F elevation and the PRL drop were more pronounced (p less than 0.001). After placental separation, PRL levels increased slightly while F values remained unchanged. These changes in hormone levels before and during labor could be attributed to the emotional and physical stress of labor. PMID- 1752055 TI - Quality of life in gynaecological oncology. AB - In the last twenty years a new philosophy in the management of gynaecological cancer has begun: the goal of the therapy is now not only to save the life but also the patient's quality of life. To this end, on the basis of a century's experience and of progress in the oncologic field, therapies have been progressively personalized and modulated, considering both the surgical pathological staging and the effective possibilities in terms of survival and quality of life, in order to avoid over or undertreatments. Moreover, in the last few years also the patients submitted to surgery for gynaecological malignancies are beginning to ask gynaecologists for access to hormonal replacement therapy in order to prevent the symptoms typical of menopause, and physicians have to decide when that is possible. Consequently gynaecologist oncologists have to bear in mind the therapy's real cost/benefit balance for the patients, also from a psychological point of view, and in any case, treatments must be performed only if they are unquestionably useful and if they involve the patient's consciousness in choices and decisions. PMID- 1752056 TI - Growth hormone-binding proteins. PMID- 1752057 TI - Effects of sex and age on serum GH binding protein levels in normal adults. AB - OBJECTIVE: The effects of sex and age on serum growth hormone binding protein (GHBP) levels during adulthood were investigated. DESIGN: The levels of GHBP, insulin-like growth factor-I (IGF-I), and growth hormone (GH) were determined and analysed as a function of sex and age. PATIENTS: We studied 101 normal adults (45 men, aged 20-77 years; 56 women, aged 20-80 years). MEASUREMENTS: GHBP levels were determined using an Ultrogel AcA 44 minicolumn. RESULTS: During the second and third decade, GHBP levels were not different between men (22.8 +/- 1.1%) (mean +/- SE) and women (23.2 +/- 0.8%). After the age of 40 years, however, GHBP levels in men were significantly decreased (19.1 +/- 0.7%), and were lower than those in women (22.7 +/- 0.9%). IGF-I levels correlated positively with GHBP levels in men (r = 0.51, P less than 0.01) but not in women (r = 0.16, NS). CONCLUSIONS: These results indicate that both sex and age may have some effects on the GH-GH receptor-IGF-I axis. PMID- 1752058 TI - Antisperm antibodies in the polyglandular autoimmune (PGA) syndrome type I: response to cyclical steroid therapy. AB - OBJECTIVE: To determine if cyclical intermediate dose steroid therapy could improve semen parameters in an infertile man with sperm autoimmunity associated with the polyglandular autoimmune (PGA) syndrome. DESIGN: Sperm agglutination studies performed before, during and after three courses of cyclical intermediate dose prednisolone therapy. PATIENT: A twenty-six-year old man with polyglandular autoimmune syndrome, consisting of Addison's disease, hypoparathyroidism, chronic mucocutaneous candidiasis and alopecia totalis, presented with infertility. He had normal endocrine testicular function but severe exocrine failure evidenced by a low sperm count (4.5 x 10(6)/ml), zero motility and universal sperm agglutination. MEASUREMENTS: Sperm agglutination tests. RESULTS: At presentation the gelatin agglutination test (GAT) was strongly positive in serum (1/1204) and seminal plasma (1/64) as was the tray agglutination test (TAT) (1/32). The patient's wife had a regular menstrual cycle with normal luteal phase progesterone levels. Following three courses of cyclical prednisolone (20 mg twice daily on days 1-10 of wife's cycle, and 5 mg on days 11 and 12), sperm quantity and motility improved considerably (12 x 10(6)/ml, 40% respectively) and sperm agglutination tests became negative. After a fourth course of therapy the patient's wife became pregnant. Three months post-treatment sperm motility was very low again and agglutinating activity in serum and seminal plasma increased. CONCLUSIONS: This is the first case of male infertility due to sperm autoimmunity in association with the PGA syndrome type 1. The immunosuppressive action of cyclical intermediate dose steroid therapy led to a significant quantitative and qualitative improvement in semen parameters. PMID- 1752059 TI - The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro-endocrine bronchial tumours in man. AB - OBJECTIVE: Bronchial tumours are the most frequent cause of the ectopic ACTH syndrome. Two types of tumours are classically responsible: the relatively benign carcinoids and the highly aggressive small cell carcinomas. Both have neuro endocrine features and are thought to originate from the endocrine component of the bronchial tree. Our objective was to assess the sensitivity of 7B2 and secretogranin 1 as new biochemical markers of neuro-endocrine differentiation in these tumours in comparison with gastrin releasing peptide. METHODS: Tissue concentration of 7B2, secretogranin 1 fragments (GAWK and CCB), gastrin releasing peptide and beta-endorphin were measured in normal human lung (n = 4), bronchial carcinoid tumours with (n = 5) and without (n = 15) the ectopic ACTH syndrome, small cell carcinomas (n = 2), squamous cell carcinomas (n = 11) and adenocarcinomas (n = 6). Molecular weight forms of immunoreactive--ACTH, -GAWK, gastrin releasing peptide, and -7B2 were also examined using gel exclusion chromatography and Western blot analysis. RESULTS: We detected 7B2 immunoreactivity in 19 of 22 neuro-endocrine lung tumours (with values ranging from less than 5 to 555 fmol/mg wet weight tissue), CCB immunoreactivity in 20 of 22 tumours with neuro-endocrine features (with values ranging from less than 5 to 19,875 fmol mg wet weight tissue) and gastrin releasing peptide immunoreactivity in 10 of 22 neuro-endocrine lung tumors (with values ranging from less than 5 to 11,132 fmol/mg wet weight tissue). Immunoreactive 7B2 and CCB were detected neither in tumours with non-endocrine features, nor in the four normal lung specimens. Differing molecular weight forms of immunoreactive 7B2 in two bronchial carcinoids associated with the ectopic ACTH syndrome showed a predominant signal corresponding to a molecular weight of 22 kDa; in addition, a second signal of 19 kDa was also present. The differing molecular weight forms of immunoreactive ACTH related peptides in the five tumours responsible for the ectopic ACTH syndrome showed, in addition to ACTH1-39, the constant presence in variable proportions of corticotrophin-like intermediary lobe peptide (or ACTH18 39). The differing molecular weight forms of immunoreactive GAWK showed heterogeneous results with materials eluting at Kav of 0, 0.3 and 0.4 respectively. In the three bronchial carcinoids studied, two immunoreactive gastrin releasing peptide molecular weight forms were always found at Kav of 0.5 and 0.85 corresponding to gastrin releasing peptide and its fragment 14-27 respectively. CONCLUSION: Our results show that 7B2 and the two fragments of secretogranin 1 (GAWK and CCB) are the best biochemical markers of neuro endocrine differentiation in human lung tumours. PMID- 1752060 TI - Serum and follicular fluid insulin like growth factors I and II during growth hormone co-treatment for in-vitro fertilization and embryo transfer. AB - OBJECTIVE: We wished to assess the changes in serum IGF-I and IGF-II concentrations during gonadotrophin treatment alone or with additional GH treatment and to compare follicular fluid IGF-I and IGF-II concentrations in the two treatment groups. DESIGN: We performed an open study of co-treatment with GH and subsequently a randomized double blind comparison of addition of placebo or GH to clomiphene citrate and gonadotrophins. PATIENTS: We studied previously poor responders to superovulation regimens for in-vitro fertilization and embryo transfer, six women in an open study, four of whom had ultrasound diagnosed polycystic ovaries, and 17 women in a double blind study, 12 of whom had polycystic ovaries. MEASUREMENTS: We measured serum IGF-I and IGF-II concentrations throughout treatment cycles. Follicular fluid concentrations were measured at the time of oocyte recovery. RESULTS: Neither serum IGF-I nor IGF-II concentrations were altered by gonadotrophin treatment alone. However, co treatment with GH led to a significant rise in serum IGF-I concentrations in women with ultrasound diagnosed polycystic ovaries. Concentrations of IGF-I and IGF-II in follicular fluid were lower than in serum, although follicular fluid IGF-I concentrations were higher in women receiving GH than in those receiving placebo. CONCLUSIONS: Poor responders to superovulation regimens may have an abnormality of growth factor response. GH co-treatment leads to an increase in circulating IGF-I concentrations in women with polycystic ovaries but our results do not support the hypothesis that GH stimulates IGF-I production in the human ovary. PMID- 1752061 TI - Treatment with biosynthetic growth hormone of short thalassaemic patients with impaired growth hormone secretion. AB - OBJECTIVE: Impairment of linear growth is a common clinical feature in patients with beta-thalassaemia major. Although growth hormone secretion appears to be normal in many short thalassaemic patients, it proves to be deficient in some of them. In these cases, administration of biosynthetic growth hormone seems justified. The aim of this study was to evaluate the effect of such treatment in a group of patients with beta-thalassaemia major presenting with growth failure and impairment of growth hormone secretion. DESIGN: Recombinant human growth hormone, 0.6 U/kg body weight per week, given subcutaneously in three divided doses, was administered for 12 months. PATIENTS: Eight prepubertal patients with beta-thalassaemia major, presenting with severe growth retardation and impaired growth hormone secretion in response to provocative stimuli (insulin-induced hypoglycaemia, L-dopa and growth hormone-releasing hormone), were investigated. MEASUREMENTS: Height and pubertal stage of the patients, as well as plasma levels of insulin-like growth factor I, were determined before, during and after biosynthetic growth hormone treatment. RESULTS: During the first 6 months of therapy, a significant increase of growth velocity was observed, from a mean pretreatment value of 2.1 +/- 0.45 cm/year to a value of 4.8 +/- 0.66 cm/year (P less than 0.002). Mean growth rate at 12 months (4.1 +/- 0.50 cm/year), though slightly decreased in comparison to that recorded at 6 months, was still significantly higher than basal (P less than 0.001). A significant increase in plasma levels of insulin-like growth factor I was recorded during treatment (2.82 +/- 0.47 vs 0.96 +/- 0.22 U/ml, P less than 0.005). No side-effects, adverse reactions or alterations in routine laboratory examinations ensued during or after therapy. CONCLUSIONS: It appears from these data that biosynthetic growth hormone administration is worth serious consideration in patients with beta thalassaemia major presenting growth retardation and impaired growth hormone secretion. PMID- 1752062 TI - Inhibin and age in men. AB - OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men. PMID- 1752063 TI - Ketoconazole treatment in Cushing's syndrome: experience in 34 patients. AB - OBJECTIVE: Ketoconazole treatment of Cushing's syndrome has been reported in single cases and a few small groups of 5-8 patients. We report our experience in 34 patients. DESIGN: Clinical study, with pretreatment and post-treatment evaluations. PATIENTS: Out of 67 patients with Cushing's syndrome admitted during the last 6 years, 34 (28 females/six males; age range 14-67 years) received ketoconazole as a palliative treatment due to severe clinical conditions or management of the disease while awaiting results of definitive therapy. MEASUREMENTS: Urinary cortisol, plasma cortisol and ACTH, and routine chemistry were measured every week for 4 weeks, and then once a month. RESULTS: Comparing the last values (mean +/- SEM) during treatment with baseline, urinary cortisol decreased from 1296 +/- 176 to 270 +/- 69 nmol/d (n = 34; P less than 0.001); plasma cortisol decreased from 672 +/- 31 to 549 +/- 35 nmol/l (n = 34; P less than 0.001). For patients with pituitary-dependent Cushing's syndrome, urinary cortisol decreased from 1073 +/- 126 to 200 +/- 21 nmol/d (n = 28; P less than 0.001) while plasma ACTH changed from 12.5 +/- 1.3 to 11.3 +/- 0.8 pmol/l (n = 26; not significant). Twelve patients were treated for more than 6 months, and those with pituitary-dependent disease all received pituitary radiation therapy, except the two who eventually escaped pharmacological control. One additional patient with adrenal carcinoma and one with ectopic ACTH syndrome showed lack of control of urinary cortisol levels. Ketoconazole was withdrawn within the first week in two patients for allergic reaction and acute liver toxicity. Other side effects included: asymptomatic liver function abnormalities in three patients; gastrointestinal symptoms in four; worsening of gynaecomastia in one. Rapid clinical improvement was observed together with the normalization of urinary cortisol levels, with regression of symptoms such as diabetes mellitus, hypertension, hypokalaemia, and restoration of well being. CONCLUSIONS: These data confirm that ketoconazole is valuable in the management of hypercortisolism, provided that patients are closely watched to exclude those who may develop liver toxicity and to prevent the occurrence of adrenal insufficiency. PMID- 1752064 TI - beta-Endorphin and adrenocortical function in obesity. AB - OBJECTIVE: To test the hypothesis that the hyperendorphinaemia in obesity originates from outside the pituitary. DESIGN: Intravenous administration of corticotrophin-releasing hormone (CRH) after overnight suppression with 2 mg of dexamethasone in normal-weight controls and in obese subjects before and after weight reduction. PATIENTS: Eleven obese females, age (mean +/- SEM) 30 +/- 2.1 years, body mass index (BMI) 41.2 +/- 1.9 kg/m2. Eight normal-weight females served as controls, age 26 +/- 2.1 years, BMI 21.4 +/- 0.5 kg/m2. Five obese subjects were also studied after weight loss of 18.4 +/- 1.0% of original weight. MEASUREMENTS: Plasma beta-endorphin, ACTH and cortisol. Cortisol production rate in 24-hour urine. Basal (without dexamethasone suppression) plasma beta-endorphin levels. RESULTS: Basal (without dexamethasone suppression) beta-endorphin levels were 7.7 +/- 0.8 pmol/l in the obese and 3.8 +/- 0.5 pmol/l in the control subjects (P less than 0.005). The degree of suppression of beta-endorphin after dexamethasone was similar in the obese (23.2 +/- 3.7%) and in the control subjects (28.2 +/- 0.12%). Administration of CRH following dexamethasone suppression resulted in a small but significant increase of plasma beta-endorphin in both obese (from 1.55 +/- 0.12 to 2.32 +/- 0.28 pmol/l) and control subjects (from 0.98 +/- 0.24 to 1.69 +/- 0.33 pmol/l). The groups did not differ regarding this response, nor regarding the release of ACTH and cortisol after CRH. Cortisol production rate was higher (P less than 0.001) in the obese (68.7 +/- 3.3 mumol/24 h) than in the controls (40.0 +/- 3.0 mumol/24 h). No correlation between cortisol production rate and basal beta-endorphin levels was found. Weight loss appeared to have no influence on cortisol production rate, basal beta endorphin levels, or on the responses to dexamethasone or CRH. CONCLUSIONS: Plasma beta-endorphin in obese subjects can be affected by manipulations of the hypothalamic-pituitary-adrenocortical axis; the hypothesis that the hyperendorphinaemia of obesity originates from outside the pituitary cannot be confirmed. PMID- 1752065 TI - Regulation of hunger and satiety in man. AB - From the perspective presented in this minireview, it is clear that a variety of psychological and physiological factors interact to regulate feeding behavior. The hunger-satiety cycle involves preabsorptive and postabsorptive humoral and neuronal mechanisms. Psychological, social and environmental factors, nutrients and metabolical processes and gastric contractions originate hunger signals. Eating, in turn, activates inhibitory signals to produce satiety. Because of the delay between the swallowing of food and the digestion of food, the satiety mechanism requires a short-term signal to prevent over-eating. This short-term satiety signal is activated by psychological factors (such as sensory-specific satiety), chemical senses (taste and smell) and mechanical factors related to the process of swallowing and gastric distension. The long-term satiety is then activated by the chemoreception of nutrients and peptides by the gastrointestinal system (including the liver), the CNS and by intrinsic CNS mechanisms. The fine regulation of feeding behavior through these mechanisms will ensure the maintenance of normal energy metabolism. It is important to note, however, that despite all the efforts that have gone into the study of peripheral and central mechanisms of ingestive behavior--expressed in thousands of publications related to the anatomy, chemistry and metabolism, physiology and behavioral aspects of feeding--we will lack an understanding of the interactions among signals within a system or among different systems. PMID- 1752066 TI - Abdominal tuberculosis: a critical review. PMID- 1752067 TI - Etiology, pathogenesis and therapy of pigment gallstones. PMID- 1752068 TI - Portal hypertensive gastropathy. PMID- 1752069 TI - Hepatic fibrosis and its serum markers: a review. AB - Hepatic fibrosis is characterized by a progressive increase in extracellular matrix in the liver, formed by collagens, proteoglycans and glycoproteins, qualitatively similar but quantitatively different from that in normal liver. A great number of matrix-related substances have been investigated in serum in order to identify reliable serum markers of liver fibroplasia. Among the various cleavage products of collagen precursor, the NPIIIP collagen is at present considered the most reliable serum marker of active fibrogenesis in liver, useful in monitoring the progression of fibrosis and in assessing the therapeutic efficacy of antifibrotic drugs. Lam-P1 and type IV collagen are now regarded as putative markers of basement membrane formation and sinusoids capillarization, an important pathological process in fibrosing disease, related to the impairment of hepatic circulation. Other serum-measured matrix-related substances, e.g. enzymes involved in collagen metabolism, fibronectin and proteoglycans, have not proved to reflect liver fibroplasia reliably. In spite of the availability of useful serum markers, the assessment of hepatic fibrosis is still based on liver biopsy. PMID- 1752070 TI - Morphologic findings in "zero-hour" biopsies of renal transplants. AB - The extreme lack of renal grafts for transplantation stimulated us to analyze how strict the selection criteria of kidney donors must be. We investigated therefore if preexisting lesions in renal grafts influence initial and late renal function. 147 zero-hour biopsies of 101 donors (mean age 33, from 6-64 years) were examined. By ligh microscopy 38% of biopsies showed no, 44% showed nonspecific and 18% specific lesions. Nonspecific lesions comprised intimal fibrosis of small arteries in 44%, interstitial fibrosis in 8% and an arteriolar hyalinosis in 29%. Out of 102 immunohistologically examined biopsies 74.5% showed nonspecific IgM/C3 deposits in glomeruli and/or arterioles. An age dependent decrease of normal renal biopsies was found which was most evident in donors older than 40 years. Specific findings consisted of glomerulosclerosis (n = 4), glomerulonephritis (n = 11), intravascular coagulation (n = 10) and eclamptic kidney (n = 1). In case of nonspecific immunohistologic findings and in glomerulonephritis rebiopsies showed that antigen deposits usually disappeared within 4 months. Independent of morphologic findings 82% of transplant recipients had a good initial and late renal function. Since donor age, glomerulosclerosis, glomerulonephritis, intravascular coagulation or eclamptic changes seem not to compromise renal function after transplantation a more liberal choice of donors should be considered. PMID- 1752071 TI - A membranous nephropathy associated with adult polycystic kidney disease. AB - A 53-year-old woman with adult polycystic kidney disease (PKD) developed a nephrotic syndrome. Evaluation of the renal biopsy specimens showed typical findings of membranous nephropathy (MN). There are few reports of nephrotic syndrome associated with PKD and only one proved to be MN. The possible mechanism of the association of PKD with MN was evaluated. Autoantibodies against the brush border were not detected in this patient's serum by indirect immunofluorescence. Three monoclonal antibodies against the tubular brush border and epithelial cell of distal tubulus did not react with subepithelial deposits in the biopsy specimen. Therefore tubular brush border antigen which was reported to induce membranous nephropathy was not detected in the immune complexes deposited in the glomeruli. So we could not determine any direct relationship between PKD and MN. The reaction of antibodies against basement membrane components (type IV collagen, laminin, fibronectin, heparansulfate proteoglycan) with the basement membranes of the cysts was evaluated by indirect immunofluorescence. The reaction with anti-heparansulfate proteoglycan antibody was decreased compared with normal tubular basement membrane. The reactivity to anti-fibronectin antibody was remarkably increased in the cystic walls, tubules, and interstitium. Changes of tubular basement membrane antigens was observed in PKD. PMID- 1752072 TI - Urine kallikrein excretion in relation to renal sodium handling in minimal change nephrotic syndrome. AB - Twenty-four-hour urine kallikrein excretion (Uka), urine protein excretion, renal sodium handling, and the activity of the renin-angiotensin-aldosterone system were serially studied in 11 children at three different stages of the minimal change nephrotic syndrome (MCNS)-edema forming state, proteinuric steady state in which a relapse of the disease was just starting but no edema as yet and remission. The value for Uka was significantly increased in the edema forming state in contrast to the normal values of proteinuric steady state and remission. Serum sodium concentration was only decreased in the edema forming state and the degree of hypoalbuminemia and proteinuria did not differ between the edema forming and proteinuric steady states. Urine volume, absolute and fractional sodium excretion were significantly decreased in the edema forming and proteinuric steady states as compared with those in remission, suggesting that sodium retention was present in both states of the disease although the change in these parameters was more profound in the edema forming state than in the proteinuric steady state. Creatinine clearance did not differ among each stage of the disease. Plasma renin activity and plasma aldosterone concentration were significantly increased in the edema forming state as compared with those in the proteinuric steady state and remission. Plasma renin activity and plasma aldosterone concentration were significantly correlated directly with Uka and plasma aldosterone concentration was correlated inversely with urine sodium excretion. No relation was noted between Uka and other variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752073 TI - Repeated albumin infusions do not lower blood pressure in preeclampsia. AB - Since intravascular volume contraction is regarded as an important pathological feature in preeclampsia, it has been proposed that plasma volume expansion could be a therapeutic manoeuver that interrupts the pathogenetic chain of hypovolemia inducing increased vascular resistance. Furthermore, tissue perfusion should be improved and, if albumin is used as plasma expander agent, interstitial edema should also be reduced. We report the results observed in an open pilot study in ten preeclamptic patients treated with daily albumin infusions (0.4 to 1 g/kg) from 7 to 36 days. No acute effects were shown on blood pressure, and the need for antihypertensive therapies did not decrease in the following days. Serial evaluation after at least five or ten days of repeated albumin infusions did not show stable changes in electrolytes excretion, renal clearances, serum protein concentration and hematocrit value, nor in aldosterone, renin and atrial natriuretic peptide basal levels, while proteinuria tended to increase. Uteroplacental and fetoplacental blood flow acutely ameliorated in 3 cases only after albumin 1 g/Kg, but reached basal values again on the next day. The clinical implications are that daily albumin infusions with this schedule dosage do not lower blood pressure and that they are unable to induce stable changes in renal function, uteroplacental and fetoplacental resistance. No maternal complications were observed during the conservative management, but fetal mortality was high (6/10). Given the uncontrolled study, we cannot know whether similar results had been achieved by conventional therapy only. PMID- 1752074 TI - Renal failure and cholesterol crystal embolization: a report of 4 surviving cases and a review of the literature. AB - Four patients with end-stage renal failure (suspected to be) caused by cholesterol crystal emboli are described. Although cholesterol crystal embolization is generally considered to be fatal specifically when it is associated with renal failure, all four patients survived and in three renal function improved after periods of 3 weeks to 14 months of hemo- or peritoneal dialysis. The literature on cholesterol crystal embolization is reviewed and possible mechanisms of (partial) recovery of renal function are discussed. PMID- 1752075 TI - Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. AB - Twice weekly subcutaneous (s.c.) administration of recombinant human erythropoietin (rHuEPO) is effective in reversing renal anemia in CAPD patients. However the optimal frequency of administration has not been established. It would be more convenient to give rHuEPO by once weekly rather than twice weekly injection. We have therefore compared the effect of twice weekly versus once weekly s.c. administration of rHuEPO. Two groups of 10 CAPD patients were given the same starting dose of s.c. rHuEPO (100 U/kg body wt/week) either as a single weekly dose or twice weekly in divided doses. The rHuEPO dosage was then adjusted according to the hematologic response. The aim was to increase hemoglobin levels by about 1 g/dl per month. The target hemoglobin was 10 g/dl. After 16 weeks of treatment with rHuEPO, the hemoglobin levels rose from 6.6 +/- 1.2 (mean +/- SD) to 10.1 +/- 1.1 g/dl in the once weekly group and from 6.4 +/- 0.8 to 10.2 +/- 1.1 g/dl in the twice weekly group. The average doses of rHuEPO used during the study were 84 +/- 16 and 88 +/- 15 U/kg body wt/wk for the once weekly and twice weekly groups respectively. Subcutaneous administration of low dose rHuEPO is effective in reversing renal anemia. Similar responses were obtained with once weekly and twice weekly regimens. It is therefore acceptable and convenient for patients to receive one weekly s.c. injection of rHuEPO for the treatment of renal anemia. PMID- 1752076 TI - Effect of recombinant human erythropoietin (rHuEpo) on the hemostatic system in chronic hemodialysis patients. AB - Hemostatic measurements were undertaken in eight chronic hemodialysis uremic patients on recombinant human erythropoietin (rHuEpo). Same measurements were repeated in another seven patients in whom anemia was corrected by the transfusion of red blood cells. The correction of the anemia by rHuEpo therapy was accompanied by 1. correction of the prolonged Simplate Bleeding Time (BT) to normal less than 10.0, minutes after 16 weeks of rHuEpo treatment; 2. significant increases in the levels of fibrinogen, clotting FVIII:C, vWF:antigen, vWF:ristocetin cofactor and platelet count; 3. enhanced aggregation responses to ADP, adrenaline, arachidonic acid, collagen and ristocetin. There was no significant fluctuation in other coagulation parameters PT, APTT, TT, reptilase time and antithrombin III and plasma fibrinogen. In patients who were treated with RBC transfusion and despite the correction of the anemia, the bleeding time shortened significantly but not corrected, mean BT before and after RBC transfusion was 17.1 +/- 1.4 and 11.6 +/- 1.9 minutes respectively. Besides there was significant elevation of vWF:Ricofactor levels but not FVIII:C, vWF:Ag or platelet count. Platelet aggregation responses to ADP remained unchanged. It is concluded that significant elevations of FVIII:related activities, plasma fibrinogen, improved platelet aggregability and correction of the BT are salient hemostatic changes that follow rHuEpo therapy in uremic patients. PMID- 1752077 TI - Iatrogenic hypercalcemia in hemodialysis patients. AB - Calcium carbonate is frequently used in large doses as a phosphorus binder in hemodialysis patients, which often results in hypercalcemia. In most studies in which calcium carbonate is prescribed to control serum phosphorus levels the patients are not given calcitriol. However, calcitriol may be necessary for suppression of parathyroid hormone. The risk of hypercalcemia when calcium supplements are used in conjunction with calcitriol has not previously been examined in detail. We reviewed the charts of 74 hemodialysis patients (119 patient dialysis years) to determine the relationship of serum calcium to calcitriol, calcium therapy, and PTH levels. Twenty-eight patients (38%) were hypercalcemic at some point. Calcitriol therapy significantly increased the risk of hypercalcemia, independently of calcium therapy (p = 0.032). However, patients on a low dose of calcitriol were more than twice as likely to be hypercalcemic than patients on higher doses. Mean PTH levels were lower in the patients on the lower doses of calcitriol, indicating less severe hyperparathyroid disease. We conclude that hypercalcemia is a common complication in hemodialysis patients on calcitriol and calcium carbonate. Whether lowering the dialysate calcium, as suggested by other investigators, will successfully decrease the risk of hypercalcemia without worsening hyperparathyroidism remains to be determined. PMID- 1752078 TI - Myoglobinuria after KENDOU training. PMID- 1752079 TI - Predicting outcome after childhood hemolytic uremic syndrome. PMID- 1752080 TI - Anaphylactoid reactions in patients on hemodiafiltration with AN69 membranes whilst receiving ACE inhibitors. PMID- 1752081 TI - Mixed inocula of mouse mammary tumour cell subpopulations result in changes of organ-specific metastasis. AB - Tumour and metastatic phenotypes, the pattern of mouse mammary tumour virus (MMTV) integration and expression, and the expression of a metastasis associated gene, nm23, were examined in three mammary tumour cell subpopulations, 66, 168 and 4526. Tumour growth, host survival, metastatic aggressiveness, and the distribution of different cell types in metastasis resulting from mixed cell inocula were also analysed. The results of these studies indicated that the cell lines were distinguishable from each other both phenotypically and genotypically. However, a rearrangement of the mammary tumour specific protooncogene, int-1, caused by MMTV was found to be a unique characteristic of the cell line 4526. Therefore, int-1 was used as a stable marker to examine the genotype of the metastatic colonies that developed in mice bearing tumours of mixed cell inocula. Highly metastatic 4526 cells influenced the metastatic range of poorly metastatic 66 cells. Line 66 cells that normally colonize only to lungs were also found to colonize liver when inoculated together with the liver-metastasizing 4526 cells. This acquired metastatic phenotype of 66 cells was transient. On the contrary, mixed cell inocula of 4526 and non-metastatic 168 cells did not produce any colony of 168 cells. The metastatic aggressiveness of 4526 cells was inhibited by both 66 and 168 cells. Furthermore, the metastatic behaviour of mixed inocula differed depending on the relative abundance of the component populations in the mixtures. These findings suggest that interaction between cells of different metastatic phenotypes may result in changes of their metastatic behaviour. PMID- 1752082 TI - The spread of human lung cancer cells on collagens and its inhibition by type III collagen. AB - The cell spreading ability of human lung cancer cells on collagen substrata was examined in comparison with normal human tracheal epithelial cells. Plastic dishes or multiwells were coated with type I, III or IV collagen gel at a concentrate of 200 micrograms/cm2. Ninety per cent of the normal cells were round on all collagens. Adenocarcinoma RERF-LC-MS and VMRC-LCD cell lines and squamous cell carcinoma VMRC-LCP cell line, which metastasize weakly after intrasplenic transplantation in nude mice, spread relatively poorly. Adenocarcinoma, A549 and SK-LU-1 and squamous cell carcinoma Calu-1 cell lines, which were highly metastatic to liver, spread well. Adenocarcinoma ABC-1 cell line, which is moderately metastatic to liver in nude mice, spread moderately. On type III collagen, three adenocarcinoma cell lines (A549, ABC-1 and VMRC-LCD) gradually started to contract after initial spreading and became round at 24 h. These results suggest that there may be a correlation between the degree of malignancy of human lung cancer cells and their spreading ability on collagen substrata, and that the cell spreading ability may be regulated by type III collagen in some lung cancer cells. PMID- 1752083 TI - Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases. AB - We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS. PMID- 1752084 TI - Effects of rotational stress on the effectiveness of cyclophosphamide and razoxane in mice bearing Lewis lung carcinoma. AB - The effects of conventional vs protected housing, and those caused by the periodic application of a psychological stressor (rotational stress, spatial disorientation) on mice kept in a protected housing, with spontaneous tumor metastasis have been determined in mice implanted with Lewis lung carcinoma as a function of tumor inoculum size and response to treatment with cyclophosphamide and razoxane. With a reduced inoculum size, tumor takes do not occur in mice kept in the protected housing, but do occur with spatial disorientation. With a larger inoculum size, tumor takes occur in all untreated mice, and the weight of spontaneous lung metastasis is significantly increased by spatial disorientation. For mice in protected housing, cyclophosphamide results in the absence of macroscopically detectable tumors in all of the treated mice, whereas the use of spatial disorientation abolishes this therapeutic action. The antimetastatic effects of razoxane are also reduced by rotational stress. These results indicate that housing conditions and a psychological stressor can control tumor takes and metastasis formation. They also indicate that host's antitumor resistance effectors, which are susceptible to neuroendocrine modulation by environmental and psychological stressors, participate to determine the effectiveness of the treatment with a cytotoxic (cyclophosphamide) and antimetastatic (razoxane) antitumor drug. PMID- 1752087 TI - Flare response in Ewing's sarcoma. AB - A 3 1/2-year-old boy had thigh pain and a leg mass. Bone scanning demonstrated intense uptake within the involved femur, but no uptake within the soft tissues or evidence of metastatic spread. Radiographs and CT scanning showed a large soft tissue mass and periosteal reaction suggestive of Ewing's sarcoma. Following chemotherapy, the patient had an apparently good clinical response. However, bone scanning showed uptake that was more intense and extensive than it was before therapy. Plain films and CT showed that the uptake was evidence of soft tissue calcification and that the mass had shrunk. This is an unusual example of the flare response to therapy because the apparent progression of the disease on bone scanning was caused by extraskeletal uptake. PMID- 1752086 TI - Role of the host tissue in the anti-invasive activity of the alkyllysophospholipid, ET-18-OCH3, in vitro. AB - The alkyllysophospholipid, racemic-l-O-octadecyl-2-O-methylglycero-3- phosphocholine (ET-18-OCH3) was previously shown to inhibit invasion of malignant cells into precultured heart fragments (PHF) in vitro. In particular, pretreatment of PHF with 10 micrograms ET-18-OCH3 for 48 h was sufficient to induce in the host tissue resistance towards invasion by mouse MO4 cells. Resistance was obvious when MO4 cells were confronted either immediately (the pretreatment experiment) or after withdrawal of the drug 7 days prior to confrontation (the reversibility experiment). In the present study, the survival of PHF cells in the pretreatment and reversibility experiments was similar to that of untreated PHF cells as determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyltetrazolium bromide (MTT) test and by the PHF explantation test. The effective anti-invasive concentration was 6 micrograms/ml in the pretreatment experiment while 3 micrograms/ml was sufficient to inhibit invasion in the reversibility experiment. Induction of resistance towards invasion in pretreated PHF was shown to occur not only with MO4 cells but also with mouse LLC-H61 Lewis lung carcinoma and mouse BW-O-Li1 T-lymphoma cells. The increase in molecular weight of N-linked cell surface glycosylpeptides (N-GP) of PHF was apparent in the pretreatment experiment and was enhanced in the reversibility experiment. This effect was completely abolished in cells obtained from pretreated PHF which were converted into a cell suspension and further cultured as a monolayer on tissue culture plastic without drug for 7 days. The results reported here provide additional evidence for the causal involvement of N-GP of the PHF host tissue in the anti-invasive activity of ET-18-OCH3 in vitro. PMID- 1752085 TI - Characterization of the invasive and metastatic phenotype in human renal cell carcinoma. AB - The purpose of these studies was to identify some characteristics of metastatic cells and deficiencies of non-metastatic cells in the heterogeneous SN12 human renal cell carcinoma. The SN12 parental line and several isolated variants with different metastatic potential were studied both in vivo and in vitro. We compared the ability of metastatic and non-metastatic cells to adhere to components of the extracellular matrix or to endothelial cells, to migrate and invade, to form multicell aggregates, to survive in the circulation, and to produce experimental and spontaneous lung metastases. In general, highly metastatic SN12 cells capable of producing spontaneous lung metastases demonstrated invasion through reconstituted basement membrane-coated filters; the cells also released diffusible collagenolytic activity into the culture medium that could enhance invasion by otherwise non-invasive and non-metastatic SN12 cells. In addition to enhanced invasion, metastatic cells produced more homotypic aggregation then non-metastatic cells and survived to produce experimental metastasis. Collectively, these data confirm that metastatic cells must complete all steps of the process; in this process, failure to produce metastasis is probably due to one or more deficiencies. PMID- 1752088 TI - Porous-coated acetabular component. Quantitative assessment of normal radiophosphate uptake as a function of implant age. AB - A computer-assisted quantitative analysis was undertaken of normal radiophosphate bone uptake adjacent to the porous-coated acetabular component in asymptomatic patients. Implants ranged from 1.6 to 49 months of age. In 62 hips, it was found that implants newer than 12 months of age had uptakes that were significantly greater than those 12 months or older. Between 12 and 49 months, there was no correlation with age, indicating a stabilization of the remodeling process. PMID- 1752089 TI - Visualization of suppressed thyroid tissue by Tc-99m MIBI. AB - The authors describe a case of suppressed normal thyroid tissue in a patient with autonomous toxic nodule, which was visualized by a Tc-99m MIBI thyroid scan without thyrotropin (TSH) stimulation. The findings suggest that Tc-99m MIBI can be a substitute for conventional thyroid imaging using I-131 to visualize suppressed normal thyroid tissue without TSH stimulation and its side effects. PMID- 1752090 TI - False-positive radionuclide arthroscintigraphy with a porous-coated total hip prosthesis. AB - The evaluation of a painful hip prosthesis for suspected loosening frequently requires a multi-modality approach. Radionuclide arthroscintigraphy is a valuable adjunct to contrast arthrography, demonstrating greater sensitivity than contrast arthrography in detecting loosening of the femoral component of the prosthesis. Despite its reliability in the evaluation of cemented hip prostheses, the value of arthroscintigraphy in patients with uncemented or porous-coated prostheses is undetermined. The case of a false-positive radionuclide arthroscintigram in a patient with an uncemented prosthesis is reported. The literature is briefly examined, and the potential implications regarding interpretation of arthroscintigraphy in patients with porous-coated prostheses are discussed. PMID- 1752091 TI - Tc-99m MIBI SPECT in the assessment of myocardial reperfusion after percutaneous transluminal coronary angioplasty. AB - Tc-99m MIBI SPECT was used to assess the early benefits of successful percutaneous transluminal coronary angioplasty (PTCA) in nine consecutive patients. SPECT stress studies were done by artificial cardiac pacing just prior to PTCA and 16-20 hours later, with perfusion images obtained 2-3 hours after pacing stress and Tc-99m MIBI injection. Angiographic restenosis was demonstrated in three patients at a later date, and all of these showed no significant improvement on the perfusion study after PTCA. All four patients asymptomatic at 7 months following PTCA had an average 15% improvement in segmental perfusion after the procedure. In two patients symptomatic after PTCA, one showed angiographic patency and had greater than 15% improvement in perfusion, while the second showed no scintigraphic improvement (no angiographic data obtained). This preliminary study suggests that Tc-99m MIBI is an important adjunct to angiography in estimating the amount of myocardium "at risk" before and after PTCA. PMID- 1752092 TI - Impact of early post-exercise myocardial redistribution of TI-201 on SPECT imaging. Preliminary observations. AB - In a series of 62 male patients undergoing exercise TI-201 SPECT myocardial scintigraphy, planar 45 degrees LAO images were acquired before (2-5 minutes postinjection, P1) and after (35 minutes postinjection, P2) the initial SPECT study in order to identify those patients with redistribution during the first 30 minutes after exercise. Consensus interpretation by four readers identified early redistribution (between P1 and P2) in 11 patients (18%), rated major (change of greater than 1.5 scoring unit) in five and minor (change of 1-1.5 scoring unit) in six. Only one patient (2%) showed major early redistribution that could not be appreciated on corresponding SPECT images. In this preliminary investigation, early thallium redistribution sufficient to affect identification of significant exercise-induced ischemia on SPECT imaging was infrequent and of limited clinical importance. PMID- 1752093 TI - Scintigraphic manifestation of iliotibial band injury in an endurance athlete. AB - The scintigraphic appearance of an overuse injury at the insertion of the iliotibial band is described. This injury was depicted on three-phase bone scintigraphy as focally increased radionuclide concentration in the anterolateral tibial condyle (lateral tibial tubercle) where the iliotibial band inserts. Overuse injuries involving the insertion of the iliotibial band are uncommon and are not to be confused with a stress fracture or other bony lesion involving the lateral tibial condyle. PMID- 1752094 TI - Early and delayed I-123 IMP SPECT in epileptic patients with partial seizures and normal CT. AB - Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG. PMID- 1752095 TI - Demonstration of increased bone metabolism in melorheostosis by multiphase bone scanning. AB - The multiphase bone scan features of melorheostosis are presented. Early increased tracer delivery demonstrated by blood pool imaging supports the concept of ongoing accelerated bony metabolism as a cause of tracer uptake within the osteosclerotic lesions of melorheostosis. There is excellent correlation between the scintigraphic and radiographic distribution of these lesions. PMID- 1752096 TI - SPECT anti-CEA monoclonal antibody detection of occult colorectal carcinoma metastases. AB - Radioimmunodetection (RAID) using Tc-99m labeled Fab' fragments of the anti-CEA monoclonal antibody IMMU-4 was performed in a 68-year-old man for preoperative evaluation of colonic metastases. Planar images at 3 and 18 hours showed uptake within known metastases in the left lobe of the liver that had been observed with CT and at surgery during the preceding month. SPECT images at 3 hours demonstrated two additional unsuspected lesions. All sites were surgically confirmed the following day using intraoperative sonographic guidance, with the smallest occult lesion measuring only 6 x 9 mm. This case illustrates the limitations of CT and surgery, the potential of RAID for the detection of occult metastases, the increased sensitivity of SPECT over planar images for detecting lesions less than 1 cm in diameter, and the value of intraoperative guidance for small nonpalpable lesions. PMID- 1752097 TI - Hepatodiaphragmatic colonic interposition (Chilaiditi's syndrome) demonstrated on Tc-99m DISIDA scan. PMID- 1752098 TI - Tuberculous lymphadenitis In-111 leukocyte and Ga-67 imaging. PMID- 1752099 TI - Abscess mimicking normal spleen on In-111 WBC scan. PMID- 1752100 TI - Aneurysmal dilatation of portal vein demonstrated on radionuclide hepatic scintiangiogram. PMID- 1752101 TI - Ga-67 citrate and Tc-99m HMPAO leukocyte scanning in extrapulmonary tuberculosis. PMID- 1752102 TI - Spontaneous calcaneal fracture in osteoporosis without fluoride therapy. PMID- 1752103 TI - Radiographic and scintigraphic demonstration of mono-ostotic fibrous dysplasia of the skull. Advantage of SPECT imaging. PMID- 1752104 TI - Tc-99m labeled RBC scan in Maffucci's syndrome. PMID- 1752105 TI - Complementary imaging modalities in the diagnosis of a mycotic aneurysm. PMID- 1752106 TI - Bridging the gender gap in research. PMID- 1752107 TI - Sports pharmacology. PMID- 1752108 TI - Individual variability in concentrations of urinary sulindac sulfide. AB - Among 70 patients with arthritis who were receiving satisfactory maintenance therapy with sulindac (300 to 400 mg daily), 64% had no detectable sulindac sulfide (active metabolite) in one to four random urine specimens. However, 36% had 1.0 to 7.8 (mean, 2.2 +/- 1.4) micrograms/ml sulindac sulfide in urine, similar to the therapeutically effective concentrations found in 24 concurrent plasma specimens (1.4 to 9.0 micrograms/ml). Ten patients had sulindac sulfide in only one or two of two to four urine specimens. Thus, 36% of the patients had pharmacodynamically significant concentrations of sulindac sulfide in urine, presumably capable of suppressing the cyclooxygenase pathway responsible for prostaglandin synthesis in the kidney and elsewhere. The findings suggest individual variability in the capacity for renal oxidation of sulindac sulfide to inactive metabolites, perhaps related to genetic or environmental factors or both. These findings may help to explain conflicting reports on the effects of sulindac on urinary prostaglandins and renal function. PMID- 1752109 TI - Pharmacokinetic and dynamic correlates of intravenous alprazolam challenge. AB - The concentration-effect relationship of alprazolam plasma concentration and growth hormone changes was studied in six healthy volunteers by use of three different intravenous bolus doses of alprazolam (0.003, 0.007, and 0.02 mg/kg) in a random blind order. There was a linear increase in peak concentration (Cmax) and area under the curve (AUC) of alprazolam with increasing dose (r = 0.96). There was no significant correlation between alprazolam Cmax and effect on growth hormone measured as either maximum increase or maximum percentage change from baseline. There was, however, an overall positive correlation (r = 0.58) between the AUC values of alprazolam and growth hormone from 0 to 120 minutes, although the relative degree of increased AUC of growth hormone with increasing AUC of alprazolam varied greatly across individuals. The difficulties of interpreting the mechanisms underlying differential growth hormone responses even when concentration of stimulus is controlled are discussed. PMID- 1752110 TI - Human liver xanthine oxidase: nature and extent of individual variation. AB - Xanthine oxidase catalyzes the biotransformation of many drugs, including the thiopurines and methyl-xanthines. We used a sensitive radiochemical assay to determine optimal conditions for the assay of human liver xanthine oxidase activity. We then used those assay conditions to study the nature and extent of individual variation of xanthine oxidase activity in 189 samples of hepatic tissue from patients undergoing clinically indicated partial hepatectomy or open liver biopsy. The average hepatic xanthine oxidase activity was 21% higher in samples from male patients than in those from female patients (1.27 +/- 0.43 [mean +/- SD, n = 92] versus 1.05 +/- 0.38 U/gm tissue [n = 97, p less than 0.0001], respectively). Seventy-nine of these tissue samples had been obtained from patients with normal liver function studies and normal serum creatinine values. Average xanthine oxidase activity in these 79 samples remained approximately 20% higher for men than for women (1.35 +/- 0.38 versus 1.12 +/- 0.33 U/gm tissue, respectively). Probit analysis of the data for samples from patients with normal liver function studies and normal creatinine values suggested the presence of a subgroup of samples with relatively low xanthine oxidase activity in 21% (9 of 42) of male patients and 27% (10 of 37) of female patients. These observations may have implications with regard to individual variation in the biotransformation of drugs metabolized by xanthine oxidase. PMID- 1752111 TI - Pharmacokinetics and pharmacodynamics of cisapride in patients undergoing hemodialysis. AB - Twenty-two patients who were receiving hemodialysis were studied in three groups of eight subjects each to assess the pharmacokinetics during the dialysis-free interval and during hemodialysis treatment and to assess the pharmacodynamics of cisapride. Cisapride and its metabolite norcisapride were measured by use of HPLC and gas chromatography, respectively. The pharmacodynamic effect of cisapride was measured by means of radionuclide gastric emptying. After a single oral dose of 20 mg the terminal half-life of cisapride was 9.6 +/- 3.3 hours, the volume of distribution was 4.8 +/- 3.3 L/kg, the total oral plasma clearance was 380 +/- 161 ml/min, the area under the curve was 1024 +/- 447 ng.hr/ml (mean +/- SD). Norcisapride only could be detected in the dialysate (0.36 +/- 0.067 mg) and was eliminated by a hemodialysis clearance of 34.7 +/- 7.9 ml/min. Cisapride reduced gastric retention from 77.6% +/- 21.1% to 43.7% +/- 18.2% of maximum filling (40 minutes after meals) and normalized the abnormal gastric emptying time in patients receiving dialysis. Cisapride dosage adjustment or substitution after hemodialysis is not necessary. PMID- 1752112 TI - Influence of rifampin on the pharmacokinetics of pefloxacin. AB - Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12 hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable. PMID- 1752113 TI - Vancomycin pharmacokinetics in acute renal failure: preservation of nonrenal clearance. AB - INTRODUCTION: The normal nonrenal clearance of vancomycin is reduced in patients with chronic renal failure (40 versus 6 ml/min). The nonrenal clearance of vancomycin in patients with acute renal failure has not been characterized extensively. PURPOSE: To prospectively determine the pharmacokinetic profile of vancomycin in anuric patients with acute renal failure who are receiving continuous venovenous hemofiltration. METHODS: Vancomycin serum samples were obtained in 10 patients immediately before and 1 and 12 hours after a 1-hour infusion. Thirteen sets of data were obtained. Vancomycin concentration data were incorporated into a first-order, single-compartment model. Determinations for the area under the serum concentration-time curve were made by the trapezoidal rule. RESULTS: Total vancomycin clearance was 28.5 +/- 6.4 ml/min (range, 17.1 to 36.6 ml/min. Hemofilter clearance was either 6.7 or 13.3 ml/min, depending on ultrafiltrate production rate (assuming a sieving coefficient of 0.8). Nonrenal clearance, calculated as total clearance minus hemofilter clearance was 16.2 +/- 7.0 ml/min (range, 3.8 to 23.3 ml/min). Total clearance did not correlate with hemofilter clearance (r = 0.1; p greater than 0.25) but correlated strongly with nonrenal clearance (r = 0.94; p less than 0.0005). Nonrenal clearance decreased significantly as the days on continuous venovenous hemofiltration increased (range, 2 to 14 days; r = 0.68; p less than 0.025). CONCLUSION: Early in the course of acute renal failure there is a substantial preservation of the normal nonrenal clearance of vancomycin. This nonrenal clearance appears to decrease with the duration of renal failure, eventually approaching the clearance observed in patients with chronic failure. PMID- 1752114 TI - Disposition of drugs in cystic fibrosis. III. Acetaminophen. AB - The disposition of acetaminophen after oral administration was investigated in adults with cystic fibrosis (n = 5) and in age-matched healthy control subjects (n = 5). The total plasma clearance of acetaminophen was found to be greater (p less than 0.025) in subjects with cystic fibrosis (0.362 +/- 0.081 L/hr/kg) than in control subjects (0.247 +/- 0.022 L/hr/kg). This difference in clearance was found to be primarily attributable to a greater metabolic clearance of acetaminophen to acetaminophen sulfate (0.080 +/- 0.023 L/hr/kg for subjects with cystic fibrosis and 0.045 +/- 0.008 L/hr/kg for control subjects; p less than 0.05) and to a greater metabolic clearance of acetaminophen to acetaminophen glucuronide (0.189 +/- 0.051 L/hr/kg for subjects with cystic fibrosis and 0.114 +/- 0.017 L/hr/kg for control subjects; p less than 0.05) in persons with cystic fibrosis. Of the mechanisms that may be responsible for these differences, the most likely is enhanced activity (in subjects with cystic fibrosis) of the transferases that mediate the metabolism of acetaminophen to acetaminophen sulfate and acetaminophen glucuronide, respectively. PMID- 1752115 TI - Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. AB - Different recombinant human erythropoietin products have been developed. Although they appear to have similar pharmacokinetics and function, these have not been directly compared. This randomized, double-blind, four-period crossover study compared the pharmacokinetics and pharmacodynamics of intravenous and subcutaneous epoetin alfa and epoetin beta in 18 normal male volunteers. As a control, three subjects received placebo treatment. After intravenous administration, the steady-state volume of distribution and beta-phase volume of distribution of epoetin beta were 7.7% and 16.9% larger than for epoetin alfa (p less than 0.05). The terminal elimination half-life after intravenous administration of epoetin beta was 20% longer than the terminal elimination half life of epoetin alfa. After subcutaneous administration there was a delayed drug absorption with epoetin beta compared with epoetin alfa (p less than 0.05). There was a small but significantly greater absolute reticulocyte response after subcutaneous epoetin beta compared with subcutaneous epoetin alfa. The findings support differences in the pharmacokinetics and function of epoetin alfa and beta that are possibly caused by differences in their glycosylation. PMID- 1752116 TI - Pharmacokinetics of recombinant human superoxide dismutase in healthy volunteers. AB - We studied the pharmacokinetics and effects of recombinant human superoxide dismutase (rhSOD) in 32 normal human volunteers after intravenous bolus doses from 1 mg/kg to 45 mg/kg in a single-blind, placebo-controlled, crossover design. The drug was well tolerated. Neither cardiovascular nor renal function, such as the echocardiographically determined cardiac index, insulin or para aminohippurate clearance, or the urinary excretion of beta 2-microglobulin or N acetylglucosaminidase, was affected. Pharmacokinetic analysis by use of noncompartmental methods showed an overall half-life of rhSOD to be about 4 hours for doses from 3 mg/kg to 45 mg/kg. The peak concentrations ranged from 24 to 837 mg/L, and urinary excretion increased from 3% to 57% of total dose after single intravenous bolus administrations of the drug from 1 mg/kg to 45 mg/kg. The mean renal clearance of rhSOD initially increased with dose then plateaued at the highest dose, whereas the nonrenal clearance decreased with dose to a plateau; total clearance remained essentially constant. The progressive increase in renal clearance may be explained by saturation of the tubular reabsorption and degradation of the protein, a mechanism previously described in animal models. PMID- 1752117 TI - Pain and hyperalgesia after intradermal injection of bradykinin in humans. AB - Pain and hyperalgesia, the perceptual campanions of tissue injury and inflammation, are thought to be in part attributable to the sensitization of primary afferent nociceptors by endogenously released chemicals, such as bradykinin. Bradykinin (0.1 to 10 nmol in 10 microliters) evoked a dose-dependent pain, hyperalgesia to heat stimuli, and wheal and flare when injected in a double blind manner into the volar forearm intradermally. Though hyperalgesia to mechanical stimuli is a conspicuous feature of inflammatory pain, none was measurable for any of the bradykinin doses in response to graded nylon monofilament probes. A second injection of bradykinin (5- or 30-minute intervals) at the same site produced markedly less pain and hyperalgesia to heat stimuli, indicating that the algesic and hyperalgesic effects of bradykinin undergo tachyphylaxis. These findings suggest that bradykinin alone cannot account for all aspects of the hyperalgesia that occurs after inflammation. PMID- 1752118 TI - Effects of lovastatin and pravastatin on sleep efficiency and sleep stages. AB - The effects on sleep of two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (40 mg lovastatin and 40 mg pravastatin) were evaluated in 12 normal subjects in a double-blind placebo-controlled sleep laboratory study. Subjects were randomly assigned to each of two parallel groups (lovastatin and pravastatin). Each parallel-group protocol consisted of 22 consecutive nights including 4 placebo-baseline nights, 2 weeks of drug administration, and 4 placebo-withdrawal nights. Lovastatin did not disturb sleep initially (nights 5 through 7) but, with continued administration (nights 16 through 18), it significantly and markedly increased wake time after sleep onset and stage 1 sleep compared with baseline. By contrast, pravastatin was not associated with sleep disturbance either initially or with continued use. Neither drug caused any sleep disturbance after withdrawal. Lovastatin's sleep disturbing effects with continued administration are attributed to its high degree of lipophilicity in contrast with the hydrophilicity of pravastatin. PMID- 1752119 TI - A problem decomposition method for efficient diagnosis and interpretation of multiple disorders. AB - Diagnosis of multiple disorders can be made more efficient by reasoning explicitly about problem decompositions. A diagnostic problem can be decomposed by hypothesizing about common and disjoint cause relationships among the given symptoms. The resulting structure exploits computational principles of causal intersection, subproblem independence, and minimal factorability to increase efficiency. By assigning structure to a problem, the symptom decomposition approach offers a new type of decision-support task called symptom interpretation. Experimental results indicate that symptom decomposition yields substantial increases in performance compared to existing methods for multidisorder diagnosis. PMID- 1752120 TI - Thomas: building Bayesian statistical expert systems to aid in clinical decision making. AB - Knowledge-based system for classical statistical analysis must separate the task of analyzing data from that of using the results of the analysis. In contrast, a Bayesian framework for building biostatistical expert system allows for the integration of the data-analytic and decision-making tasks. The architecture of such a framework entails enabling the system (1) to make its recommendations on decision-analytic grounds; (2) to construct statistical models dynamically; (3) to update a statistical model based on the user's prior beliefs and on data from, the methodological concerns evinced by, the study. This architecture permits the knowledge engineer to represent a variety of types of statistical and domain knowledge. Construction of such systems requires that the knowledge engineer reinterpret traditional statistical concerns, such as by replacing the notion of statistical significance with that of a pragmatic clinical threshold. The clinical user of such a system can interact with the system at a semantic level appropriate to her fund of methodological knowledge, rather than at the level of statistical details. We demonstrate these issues with a prototype system called THOMAS which helps a physician decision maker interpret the results of a published randomized clinical trial. PMID- 1752121 TI - An approach to evaluating the accuracy of DXplain. AB - DXplain is a computer-based decision support system which generates a differential diagnosis (ddx) from a given list of clinical manifestations (Barnett et al., J. Am. Med. Assoc. 258 (1987) 67-74). An approach was developed to evaluate the accuracy of the ddx's produced by DXplain. The first step involves the collection of 65 benchmark cases drawn from a variety of sources and authors. Despite their diverse origins, the cases share in common that they are all clinical cases upon which a consulting physician might be asked to produce a differential. This helps to ensure that the evaluation of the system will be done in an environment similar to that in which the system is actually used. In the second step, all cases are reviewed by five board-certified physicians (experts) as well as DXplain. For each case, the evaluators (experts and DXplain) produce a rank-ordered ddx list along with an indication of how strongly each disease was felt to be supported by the case findings. A scoring technique was devised which rewards concordance with the gold standard: a consensus of the evaluators' ddx lists. Each evaluator receives a score which is proportional to the degree of agreement achieved with the consensus on the ddx submitted. Preliminary results on a trial evaluation of 46 cases indicate that DXplain, on average, did well in agreeing with the consensus. Agreement was achieved both in regard to the specific diagnoses listed in the ddx and the degree to which the diseases were felt to be supported by the case findings. A discussion of some important issues in the evaluation of knowledge-based systems is undertaken. PMID- 1752122 TI - Weaning patients from mechanical ventilation. A knowledge-based system approach. AB - The WEANing PROtocol (WEANPRO) knowledge-based system assists respiratory therapists and nurses in weaning post-operative cardiovascular patients from mechanical ventilation in the intensive care unit. The knowledge contained in WEANPRO is represented by rules and is implemented in M.1 by Teknowledge, Inc. WEANPRO will run on any IBM-compatible microcomputer. WEANPRO's performance in weaning patients in the intensive care unit was evaluated three ways: (1) a statistical comparison between the mean number of arterial blood gases required to wean patients to a T-piece with and without the use of WEANPRO, (2) a critique of the suggestions offered by the system by clinicians not involved in the system development, and (3) an inspection of the users acceptance of WEANPRO in the intensive care unit. The results of the evaluations revealed that using WEANPRO significantly decreases the number of arterial blood gas analyses needed to wean patients from total dependance on mechanical ventilation to independent breathing using a T-piece. In doing so, WEANPRO's suggestions are accurate and its use is accepted by the clinicians. Currently, WEANPRO is being used in the intensive care unit at the East Unit of Baptist Memorial Hospital in Memphis, Tennessee. PMID- 1752123 TI - A computer planning model for blood platelet production and distribution. AB - We consider a class of policies for stocking hospital blood banks with units of random donor platelet concentrate ('Platelets') based upon scheduled daily deliveries from a regional blood center to replenish the platelet inventory to a fixed 'base stock' level. The measures of interest are the 'shortage rate' (the proportion of days for which the on-hand inventory at the hospital blood bank is insufficient to meet the demand) and the 'outdate rate' (the proportion of total units shipped which are not transfused within the usable life span of 5 days). Our principal results give a predictive model which relates the base stock level to the shortage rate and outdate rate. Our model uses only the mean daily demand as a parameter. It provides a basis to unify the results from other studies which have demonstrated improvements in platelet inventory management in particular hospitals and blood centers. PMID- 1752124 TI - Interactive Query Workstation: standardizing access to computer-based medical resources. AB - Methods of using multiple computer-based medical resources efficiently have previously required either the user to manage the choice of resource and terms, or specialized programming. Standardized descriptions of what resources can do and how they may be accessed would allow the creation of an interface for multiple resources. This interface would assist a user in formulating queries, accessing the resources and managing the results. This paper describes a working prototype, the Interactive Query Workstation (IQW). The IQW allows users to query multiple resources: a medical knowledge base (DXplain), a clinical database (COSTAR/MQL), a bibliographic database (MEDLINE), a cancer database (PDQ), and a drug interaction database (PDR). Descriptions of each resource were developed to allow IQW to access these resources. The descriptions are composed of information on how data are sent and received from a resource, information on types of query to which a resource can respond, and information on what types of information are needed to execute a query. These components form the basis of a standard description of resources. PMID- 1752125 TI - Distinguishing drug toxicity syndromes from medical diseases: a QMR computer based approach. AB - Drug effects can mimic a wide variety of diseases. Experts note that adverse drug reactions (ADRs) have become the 'greatest imitator' of disease in clinical medicine. Quick Medical Reference (QMR) is a decision support system providing diagnostic data about more than 600 medical diseases. Currently, QMR contains only limited drug information. Just as physicians have difficulty diagnosing ADRs, QMR has similar problems in differentiating natural disease manifestations from drug toxicity syndromes. To remedy this problem, two prototype Drug Syndromes (DS), Carbamazepine Toxicity and Penicillin Toxicity, were incorporated into the QMR Knowledge Base (KB). Using detailed case reports, we demonstrated that a DS-augmented version of QMR was successful in discriminating these DS from the other diseases in QMR's KB. The addition of DS significantly improves QMR's diagnostic performance in cases in which some of the pathologic features are the consequence of drugs. PMID- 1752126 TI - Contextual pathognomony: a computationally useful extension of pathognomony. AB - Lack of adequate focus in problem-solving is a common problem in abductive expert systems. Pathognomonic findings could theoretically provide such focus, but their rarity in most domains makes the concept computationally useless. Pople's concept of constrictor is a useful extension of the concept of pathognomony. By relaxing the focus from a disease to a class of disease, constrictors have less theoretical power than pathognomonic symptoms, but they are more ubiquitous, thus more computationally useful. Similarly, this paper introduces the concept of contextual pathognomony. Contextual pathognomony is an extension of pathognomony that takes into account the current diagnostic context. Like constrictors, contextual pathognomony is more ubiquitous, thus more computationally useful, than pathognomony. Following the description of this new concept, this paper reports and analyses an experiment showing the existence and utility of contextual pathognomony in providing focus to abductive reasoning in the domain of alloantibody identification. PMID- 1752127 TI - Modeling all dialogue system participants to generate empathetic responses. AB - A dialogue system between an expert system and its users is described which combines two recent hypotheses. First, that the dialogue system should explicitly model both the person directly interacting with the dialogue system (the agent) and the person reasoned about by the expert system (the patient) in order to communicate meaningfully with both people. Second, that a dialogue system can model the domain-related beliefs, preferences and concerns of both its users and generate responses empathetic to both. This dialogue system is called SERUM, standing for 'System for Empathetic Responses with User Models.' SERUM generates natural-language responses about attribute values of domain objects, via three transformations. First, the system converts properties of the agent and patient, and domain knowledge, into a pragmatic objective like empathy. Second, SERUM converts the pragmatic objectives into surface structure cues like object emphasis and level of technicality. Finally, SERUM converts the surface structure cues to realize text that is natural, appropriately technical and emotionally empathetic. SERUM is demonstrated in describing tests and treatments for lung disease in AIDS patients, a sensitive domain where empathetic responses may be needed. PMID- 1752128 TI - Effects of four cryoprotectants in combination with two vehicle solutions on cultured vascular endothelial cells. AB - The necessary first step in successful organ cryopreservation will be the maintenance of endothelial cell integrity during perfusion of high concentrations of cryoprotective agents (CPAs). In this report we compare the effects of incubation on cultured porcine endothelial cells at 10 degrees C for 1 h with the CPAs glycerol, dimethyl sulfoxide (Me2SO), ethanediol (EG), and propane-1,2-diol (PG) in the vehicle solutions RPS-2 (high potassium, high glucose) and HP-5NP (low potassium, high sodium), both with and without added colloids. Tritiated adenine uptake and acid phosphatase estimation of cell number were used as indicators of cell viability. HP-5NP was superior to RPS-2 except with Me2SO when the differences in viability were not significant. Adding Haemaccel to HP-5NP improved the results, but adding albumin to RPS-2 was of no significant benefit. Osmotic stress appeared to be the major problem with glycerols use. Beyond 3.0 M the toxicity of Me2SO increased dramatically but it could not be determined if this was osmotic or chemical toxicity. PG was remarkably well tolerated to 3.0 M but a sharp decrease in cell viability beyond this concentration suggests that PG may be most useful with mixtures of other CPAs. Overall, EG appeared to be the least toxic CPA and in the context of vascular preservation warrants further investigation. PMID- 1752129 TI - Chlorpromazine, quinacrine, and verapamil as donor pretreatment in liver preservation, tested in the isolated perfused rat liver. AB - Rats were pretreated with a single iv dose of chlorpromazine (CPZ) 3 mg/kg, verapamil 1 mg/kg, or quinacrine 2 mg/kg. Livers were taken out and perfused with University of Wisconsin (UW) preservation solution and stored on ice for 48 h in the UW solution before reperfusion with erythrocyte-free and colloid-free Krebs Hanseleit buffer at 38 degrees C in a nonrecirculating perfusion system for 2 h. CPZ- and quinacrine-pretreated livers produced significantly more bile than control livers and also released significantly less alanine aminotransferase into the perfusate at 30, 60, and 120 min of reperfusion. Aspartate aminotransferase levels were lower at 30 and 60 min of reperfusion for CPZ-pretreated livers but not at 120 min. The only difference between groups concerning lactate dehydrogenase (LDH) release into the perfusate was that CPZ decreased the amount of LDH released at 60 min. Total tissue water or tissue electrolyte content of the liver tissue at the end of the reperfusion did not differ between groups. In conclusion, verapamil was ineffective when given as single dose iv pretreatment to the liver donor but pretreatment with CPZ or quinacrine appeared to improve the function of the preserved liver. PMID- 1752130 TI - Effect of sugars in the preservation solution on liver storage in rats. AB - We have performed 128 rat liver transplants in order to examine the effect of sugars in preservation solutions on cold storage of rat livers. Glucose (Mw. 180), sucrose (Mw. 348), and raffinose (Mw. 594) were tested. Rat livers were preserved at 4 degrees C for 12, 16, 18, and 24 h in standard Eurocollins solution (EC solution) (solution A) or in one of three modified EC solutions in which 194 mM/liter glucose in standard EC solution was replaced by 140 mM/liter of glucose (solution B), sucrose (solution C), or raffinose (solution D). The osmolarity of the modified solutions (solution B-D) was 320 mOsm/liter. Using standard EC solution (solution A), the 1-week survival rate of rats receiving livers preserved for 12, 16, 18, or 24 h was 6/8, 4/8, 1/8, and 0/4, respectively. With solution B, in which 194 mM/liter glucose was replaced by 140 mM/liter glucose, 1 week survivors following transplantation of livers preserved for 12, 16, 18 or 24 h were 4/8, 3/8, 2/8 and 0/4, respectively. Solution C, which was identical to solution A except for the replacement of 194 mM/liter glucose by 140 mM/liter sucrose, gave the following 1-week survival rates: 5/8 for 12 h, 5/8 for 16 h, 2/8 for 18 h, and 0/4 for 24 hours preservation, respectively. Using solution D, which differed from A in the replacement of glucose by 140 mM/liter raffinose, the 1-week survival rates of rats grafted with livers preserved for 12, 16, 18, and 24 h were 6/8, 5/8, 3/8 and 0/4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752131 TI - Cryopreservation of isolated hepatocytes: intracellular ice formation under various chemical and physical conditions. AB - Kinetics of intracellular ice formation (IIF) for isolated rat hepatocytes was studied using a cryomicroscopy system. The effect of the cooling rate on IIF was investigated between 20 and 400 degrees C/min in isotonic solution. At 50 degrees C/min and below, none of the hepatocytes underwent IIF; whereas at 150 degrees C/min and above, IIF was observed throughout the entire hepatocyte population. The temperature at which 50% of hepatocytes showed IIF (50TIIF) was almost constant with an average value of -7.7 degrees C. Different behavior was seen in isothermal subzero holding temperatures in the presence of extracellular ice. 50TIIF from isothermal temperature experiments was approximately -5 degrees C as opposed to -7.7 degrees C for constant cooling rate experiments. These experiments clearly demonstrated both the time and temperature dependence of IIF. On the other hand, in cooling experiments in the absence of extracellular ice, IIF was not observed until approximately -20 degrees C (at which temperature the whole suspension was frozen spontaneously) suggesting the involvement of the external ice in the initiation of IIF. The effect of dimethyl sulfoxide (Me2SO) on IIF was also quantified. 50TIIF decreased from -7.7 degrees C in the absence of Me2SO to -16.8 degrees C in 2.0 M Me2SO for a cooling rate of 400 degrees C/min. However, the cooling rate (between 75 and 400 degrees C/min) did not significantly affect 50TIIF (-8.7 degrees C) in 0.5 M Me2SO. These results suggest that multistep protocols will be required for the cryopreservation of hepatocytes. PMID- 1752132 TI - The effects of cryopreservation on protein synthesis and membrane transport in isolated rat liver mitochondria. AB - Protein synthesizing activity and membrane transport were examined in fresh and cryopreserved isolated rat liver mitochondria. In the presence of 0.6, 1.2, and 1.8 M final concentrations of dimethyl sulfoxide (Me2SO), both metabolic parameters were considerably inhibited in the fresh samples and even more inhibited in the cryopreserved specimens. However, simple exposure to this penetrating cryoprotectant, followed by its subsequent removal by washing, did not seem to affect significantly the examined functions. When different freeze thaw regimes were investigated, it was observed that optimal recovery of protein synthesis and membrane transport functions were obtained when fast freezing took place in the absence of Me2SO. PMID- 1752133 TI - New thermal stress test to assess the viability of cryopreserved boar sperm. AB - A new, rapid, thermal stress test for assessing the viability of boar semen, requiring only 45 min of incubation at 42.5 degrees C, was developed and compared with a widely used stress test of 180 min incubation at 37 degrees C. The shorter procedure was found to have the same discriminatory ability as the standard test in assessing the effects of freezing conditions on the percentage of spermatozoa remaining motile. Neither test was able to show differences in the kinetic rating of motile sperm after freezing in relation to the glycerol concentration present during freezing. However, the new test had a greater ability to distinguish the effects of different concentrations of glycerol, over the range of 0 to 6%, and to reveal different degrees of acrosomal damage sustained during freezing. The longer procedure was unable to distinguish among glycerol concentrations from 0 to 4% with respect to acrosomal damage and produced an overall lower proportion of sperm having a normal apical ridge. The new thermal stress test thus has the advantages of greater sensitivity and more rapid execution over the test hitherto in widespread use. PMID- 1752134 TI - Insights into the cryoprotective mechanism of dimethyl sulfoxide for phospholipid bilayers. AB - Dimethyl sulfoxide (Me2SO) is a widely used cryoprotectant for biological structures such as membranes. Despite hundreds of studies on the effects of this molecule, surprisingly little is known about its cryoprotective mechanism. This study investigates the ability of various Me2SO analogs to serve as cryoprotectants for liposomes. The data show that an increase in hydrophobicity progressively reduces the cryoprotective effect of sulfoxides. Additional experiments using phospholipid vesicles of varying composition demonstrate the Me2SO is markedly less effective on liposomes carrying a net negative charge. In fact, cryoprotection by Me2SO was virtually eliminated in vesicles composed of 30% phosphatidylserine (a negatively charged lipid). Based on these results, we suggest that the polar sulfoxide moiety of Me2SO interacts electrostatically with phospholipid membranes and that this interaction is critical for Me2SO's cryoprotective effect for membranes. PMID- 1752135 TI - Enhanced survival of yeast expressing an antifreeze gene analogue after freezing. AB - Yeast, like most organisms, survives poorly under freezing conditions. It has been proposed that after rapid cooling yeast suffers a loss in viability from the recrystallization of intracellular ice. Antifreeze proteins found in the blood of certain polar fishes have been shown to be potent inhibitors of ice recrystallization at very low concentrations. We have examined the feasibility of protecting rapidly cooled yeast cells from freezing damage by inhibiting the recrystallization of intracellular ice through in vivo expression of an antifreeze analogue gene. A chemically synthesized gene encoding a protein similar to but differing from the antifreeze proteins of the fish Pseudopleuronectes americanus (winter flounder) was genetically fused to the 3' end of a truncated staphylococcal Protein A gene. When the fused gene was expressed in the budding yeast Saccharomyces cerevisiae, its cells were shown to produce a new chimeric protein that inhibited the recrystallization of ice in vitro. Yeast cells expressing the chimeric antifreeze protein showed a twofold increase in survival after rapid freezing (95 degrees C/min to -196 degrees C) and moderate rates of warming (26 to 64 degrees C/min) compared to cells lacking the chimeric protein. PMID- 1752136 TI - Intrinsic alteration of the reactive properties of arteries during hypothermia. AB - This study compares the reactive and contractile properties of helical strips of femoral arteries taken from normothermic rabbits and rabbits that were anesthetized with pentobarbital and cooled to 25 degrees C. The purpose of this comparison was to see if previous exposure to whole body hypothermia would alter vascular muscle responsiveness to norepinephrine. We found that, after 2 h of in vivo hypothermia, the hypothermic-derived vascular strips contracted more slowly, but required from 10 to 100 times less norepinephrine to have a detectable contractile response. This continued while the tissue was in vitro for at least 12 h. Although the maximal tension developed by the strips was equivalent, the ED50 values for the hypothermic-derived arteries were lower than those of the normothermic tissue. This study has identified prolonged alterations in in vitro vascular responsiveness attributable to previous exposure to whole body hypothermia, which may help to explain the disruptions of blood pressure during and following exposure of the whole body to cold. PMID- 1752137 TI - Some seasonal changes in the thecal gland in the ovaries of hibernators (Citellus citellus L.). AB - The ovaries of 36 ground squirrels were studied in March, April, July, and December. Morphological and functional seasonal characteristics of theca interna were studied by histological methods, electron microscopy, and quantitative methods for determinating the volume density and histoenzyme activity of NADH2 tetrazolium reductase, glucose-6-phosphate dehydrogenase, and delta 5-3 beta hydroxysteroid dehydrogenase. Maximal activity of theca interna as a steroid producing structure was observed during spring awakening. A significant increase in the histoenzyme activity of delta 5-3 beta-hydroxysteroid dehydrogenase in December, versus two other enzymes studied, indicated steroid synthesis in theca terna. PMID- 1752138 TI - AIDS prevention and control in China. PMID- 1752139 TI - Basic and clinical researches in microsurgery. PMID- 1752140 TI - Immunologic investigation of Chinese hemophiliacs with and without human immunodeficiency virus infection. AB - Cellular and humoral immune functions in Chinese hemophiliacs with and without human immunodeficiency virus (HIV) infection were compared with those of healthy controls. There was a significant increase in peripheral T8 cells and a significant decrease of peripheral T4 cells as well as the T4/T8 ratio in 3 hemophiliacs with HIV infection when compared with 26 hemophiliacs without HIV infection and 18 healthy controls (P less than 0.005, P less than 0.05 and P less than 0.002, respectively). In contrast, there were no statistical differences in the above mentioned parameters between hemophiliacs without HIV infection and healthy controls. All the three HIV seropositive hemophiliacs had anergy for 1:2000 OT test whereas among the 15 HIV seronegative hemophiliacs, only two had anergy for 1:2000 OT test. These results demonstrate that the immunological abnormalities of the 3 HIV seropositive hemophiliacs were attributed to HIV infection, and that even though hemophiliacs without HIV infection had been treated with blood products, their immune functions are generally normal. These findings are somewhat different from those reported abroad. This difference may be due to the fact that Chinese hemophiliacs are often treated with much smaller dose of blood products as a part of the treatment of their coagulative defects. PMID- 1752141 TI - Myocardial protective effect of captopril cardioplegia on ischemia and reperfusion injury in the isolated rabbit heart. AB - The myocardial protective effect of captopril cardioplegia was investigated through the recovery of cardiac functions, biochemical changes and ultrastructural assays in the isolated working rabbit heart after hypothermic ischemic arrest for 3 hours. Hearts were randomly divided into 3 groups with 8 in each. Another 3 groups of hearts (8 in each) were arranged for studying the biochemical changes and ultrastructure during the ischemic period. In the control group (I), the hearts were protected by the modified St. Thomas' cardioplegic solution No. I, while in Group II and III the cardioplegic solutions contained 2.3 mumol/L and 23 mumol/L captopril respectively. The results showed that the percent recoveries of cardiac function in the 23 mumol/L captopril group compared with the control group were 97.9 +/- 9.8% vs 84.9 +/- 7.3% in left ventricular peak systolic pressure (P less than 0.01), 118 +/- 33% vs 79 +/- 20% in +dp/dt max (P less than 0.01), 111 +/- 22% vs 75 +/- 18% in -dp/dt max (P less than 0.01), 145.6 +/- 44.8% vs 76.7 +/- 18% in coronary flow (P less than 0.01), 120.2 +/- 45.7% vs 36.4 +/- 22.2% in aortic flow (P less than 0.01), 127.4 +/- 27.3% vs 56.1 +/- 14% in cardiac output (P less than 0.01), and 118.2 +/- 33.5% vs 52.5 +/ 19.9% in stroke volume (P less than 0.01) respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752142 TI - Changes of plasma immuno-reactive beta-endorphin content in patients with congestive heart failure and their clinical significance. AB - Immunoreactive beta-endorphin (ir-beta-EP) content in plasma was measured by radioimmunoassay in 101 cardiac patients and 30 normal subjects. The results showed that plasma ir-beta-EP levels in patients of Class II (New York Heart Association Classification), Class III and Class IV were significantly higher than those in the normal group and those in patients of Class I (43.14 +/- 2.80, 54.25 +/- 4.47, 79.28 +/- 8.96 ng/L vs 24.23 +/- 2.13, and 24.98 +/- 3.35 ng/L, respectively, P less than 0.01). Plasma concentration of ir-beta-EP in patients complicated with atrial fibrillation was significantly higher than that in patients without atrial fibrillation (56.27 +/- 4.13 vs 44.66 +/- 3.41 ng/L, P less than 0.05). Ir-beta-EP contents in plasma were correlated positively to the cardiothoracic ratios (r = 0.63, P less than 0.001) and PEP/LVET ratios (r = 0.33, P less than 0.01), and were correlated negatively to the left ventricular ejection fraction and axis shortening (r = -0.41 and r = -0.39, P less than 0.001). These results indicated that plasma ir-beta-EP content may serve as a parameter in evaluating cardiac dysfunction. PMID- 1752143 TI - Pathological study on cerebral amyloid angiopathy. AB - The cerebral amyloid angiopathy (CAA) was pathologically confirmed in 26 cases in which there were 20 cerebral hemorrhages, 2 subarachnoid hemorrhages, 3 cerebral infarctions, and 1 subdural hematoma. The CAA mainly involved the media and extima of small and medium-sized arteries as well as the capillaries of the brain tissue. Half of all cases in our series had the CAA associated vasculopathies (CAA-AV), including microaneurysms, "double barreling", onion skin-like intima, fibrinoid necrosis, clusters of arterioles and perivascular lymphocytic infiltrations. The CAA was often accompanied with the senile plaques and neurofibrillary tangles. PMID- 1752144 TI - Localization of functional projections from corpus callosum to cerebral cortex. AB - In 30 patients with intractable generalized epilepsy treated with cerebral commissurotomy, the corpus callosum was stimulated intraoperatively at a 1 cm interval with electric current, and evoked potentials (EPs) were recorded from different areas of the brain for determining the distribution patterns of functional projections from the corpus callosum to the cerebral cortex. The surface of the corpus callosum in man was 12 cm long and it was divided into 12 segments (1 cm each). Stimulation of the first segment resulted in EPs only in the frontal lobe. Stimulation of segments 2-4 produced EPs mainly in the anterior, middle and posterior frontal lobe, anterior and central temporal lobe, rarely in parietal and occipital lobes. Stimulation of segments 5-8 induced EPs mainly in the frontal and temporal lobes, but rarely in the parietal and occipital regions; on stimulation of segments 9-11, EPs occurred only in the parietal and occipital regions. These results were confirmed electrophysiologically in 5 cats and anatomically in 8 cats. These data provide an anatomical basis for selective cerebral commissurotomy in the treatment of intractable epilepsy. Hence in patients with a concentration of epileptic discharges in the frontal lobe, the 4 anterior segments of the corpus callosum should be incised. Epileptic discharges in the frontotemporal region indicates that the middle segments should be incised and epileptic activities originating from the parieto-occipital regions can be treated effectively by selective section of the posterior corpus callosum (segments 9-12). PMID- 1752145 TI - Plasma shock wave lithotripsy of gallstones in vitro. Animal experiments and clinical application. AB - It is sometimes very difficult to extract a huge impacted stone through the T tube fistulous tract by conventional techniques with choledochoscope. To simplify the procedure, a lithotriptor PSW-G type using plasma shock wave to disintegrate the stone was designed. The efficacy to fragmentate stone was investigated both in vitro and in vivo. Stones can be shattered into pieces less than 3 mm in diameter in about 30 times of spark with lower energy ranging from 1.7-3.4 kV and 1-3 J. Animal experiments were carried out to prove the safety of the lithotriptor. There was neither interference with the cardiovascular and respiratory systems nor obvious damage to the adjacent tissue where plasma shock wave applied to break stones. Six patients with retained calculi impacted both in extra- and intra-hepatic duct were successfully treated by plasma shock wave lithotripsy. It appears very useful in dealing with a huge impacted stone in the biliary tract. PMID- 1752146 TI - Partial purification and osteoinductive activity of swine bone morphogenetic protein. AB - Bone morphogenetic protein (BMP) was isolated from the bone matrix of swine and partially purified by means of differential precipitation and molecular sieve chromatography. The molecular weight of BMP estimated by SDS-gel electrophoresis was 19,000 dalton. Bioassay by implanting two milligrams of BMP fraction into thigh muscles of mice resulted in bone formation in 100% of the experimental animals. PMID- 1752147 TI - Histopathological and ultrastructural changes of lichen sclerosus et atrophicus on the vulva. AB - Studies of 82 skin specimens from 81 cases of lichen sclerosus et atrophicus (LSA) are reported. Typical LSA pathological changes showed atrophy of the epidermis, hydropic degeneration at the basal layer, and homogenization of the collagen fibers in the superficial dermis with inflammatory cell infiltration underneath. Ultrastructural changes showed intercellular spaces enlarged, particularly near basal cells. Some mitochondria were swollen and rough endoplasmic reticula were enlarged. Some basement membranes were thinner, collagen fibers of varying diameters were arranged in irregular shapes and the fine structures had become unclear and had sometimes even disappeared. PMID- 1752148 TI - Can magnetic stimulation induce secondary cerebral hemorrhage? PMID- 1752149 TI - [Association of HLA antigens with thyrotoxic periodic paralysis]. AB - Periodic paralysis is a rare and peculiar complication of thyrotoxicosis, especially in Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked with certain immunogenetic factors. The objective of this study was to seek a genetic marker by HLA typing in Chinese patients with thyrotoxic periodic paralysis (TPP). The distribution of HLA-A, B, C, DR and DQ antigens in 20 thyrotoxic patients with periodic paralysis and 51 thyrotoxic patients without periodic paralysis was compared with that in 100 controls. The results showed that among the patients with TPP, these was a highly significantly increase of HLA-B51 frequency and B51 appeared to be linked with Cw3 in a state of dysequilibrium. PMID- 1752150 TI - [Delayed gastric emptying in diabetes mellitus]. AB - Function of gastric motility was studied in thirty one diabetes mellitus patients by testing gastric emptying time (GET). The test was performed by giving patients food labelled with 99mTc. The results showed that GET in patients with diabetes mellitus was significantly delayed as compared with that in the controls (P less than 0.001). 15 among the 31 diabetic patients had delayed GET, accounting for 48.4%. There was no difference in age, duration of the disease, treatment regimen and microvascular complications between patients with delayed GET and those with normal GET. The only difference was the obviously increased incidence of autonomic nerve dysfunction in the former group of patients (P less than 0.05). We concluded that the incidence of delayed gastric emptying time was higher in diabetic patients with autonomic neuropathy. PMID- 1752151 TI - [Relationship between free radicals and diabetic microangiopathy]. AB - Lipid peroxide (LPO) values in blood plasma, along with the glutathione peroxidase (GSH-PX) activity in whole blood and superoxide dismutase (SOD) activity in erythrocytes were determined in 50 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 33 control subjects. The mean LPO value, SOD activity, LPO/GSH-PX and LPO/SOD ratios in the diabetic patients were significantly higher than those in the control subjects. The increases of LPO value, LPO/GSH-PX and LPO/SOD ratios were more pronounced in diabetics with microangiopathy than in those without microangiopathy. Our results suggest that free radicals may be implicated in the pathogenesis of diabetic microangiopathy. PMID- 1752152 TI - [Prospective study of functional changes in the gallbladder and formation of gallstones induced by long-term treatment of somatostatin analogue SMS201-995 in patients of active acromegaly]. AB - We reports the result about the changes of function of gallbladder in 17 acromegalic patients after treatment with long-acting somatostatin analogue SMS201-995 for 3-36 months by ultrasonogram. The number of cases developed bile sludges, gallstones, chronic and acute cholecystitis was 14, 8, 10 and 1 respectively during therapy. The contractibility of gallbladder after fatty meal was inhibited in all of the patients during the course of therapy. A bolus injection of SMS201-995 with a dosage of 100 micrograms for acromegalic patients resulted in marked suppression of the contractibility of the gallbladder. Our result indicates that the decreased contractibility of the gallbladder leads to the formation of gallstones during the long-term therapy of SMS201-995. Therefore, it is important to follow the gallbladder carefully in the course of the therapy of SMS201-995. PMID- 1752153 TI - [Influences of open thoracoscopy on human body: experience in 65 cases]. AB - The influence of open thoracoscopy with fiber-bronchoscope on human body was studied in 65 patients with pleural disease. The items observed included blood pressure, Pulse rate, respiration rate, blood gas analysis and clinical manifestations. It was found that open thoracoscopy has little influence on human body and the patients tolerated it well. No severe complication was found and operative procedures might be avoided popularization of this technique is therefore suggested. PMID- 1752154 TI - [Sodium nitroprusside in treating acute high-altitude pulmonary edema]. AB - Sodium nitroprusside (NP) alone Was given to the 39 cases with acute high altitude pulmonary edema (AHPE). 33 of them (84.6%) fully recovered and 6 (15.38%) obviously improved in 72 hours. The total efficacy was 100%. There was obvious improvement in the cardiac pumping and contractile function as well as total peripheral resistance. The mean pulmonary artery pressure (MPAP) decreased from 52.22 +/- 7.51mmHg to 25.13 +/- 10.36mmHg in 3 to 5 hours after the first dose. Strophanthin K was given to another 11 cases with AHPE, But none fully recovered or obviously improved. During the 72 hours of treatment, 4 improved slightly, 4 showed no therapeutic effect and 3 became worse. The heart rate was reduced obviously and cardiac contractile function strengthened while the cardiac pumping function and total peripheral resistance had no change. Vasodilator therapy is a new method for AHPE treatment and this study shows that the NP is an ideal drug in treating AHPE and that dilation of the small pulmonary arteries by NP may explain its efficacy. PMID- 1752155 TI - [An analysis of ST segment shift in procordial leads in patients with acute inferior myocardiac infarction with and without right ventricular infarction]. AB - ST segment change in procordial leads was analysed in 58 patients with acute inferior myocardial infarction (IMI). ST segment depression in V2 lead was negatively correlated with ST segment elevation in a VF lead in patients with IMI. ST segment depression in V2 lead was not observed when IMI was accompanied by right ventricular infarction. It indicates that ST segment depression in procordial leads was the reciprocal change of ST segment elevation in inferior leads. The direction and amplitude of ST segment shift in procordial leads may be affected by the presence of right ventricular infarction (RVI). The ratio of ST V2/ST aVF less than 0.5 may suggest a diagnosis of IMI with accompanying RVI. PMID- 1752156 TI - [The difference of erythropoietin concentration in various disease]. AB - The serum concentration of erythropoietin in 79 cases with various blood diseases, uremia, chronic obstructive pulmonary disease etc was determined. At comparable degrees of anemia, patients with myelodysplastic syndrome and aplastic anemia had the highest levels of erythropoietin in our study. The high level of erythropoietin titer in patients with aplastic anemia should be taken as the nom for renal synthesis and release of this hormone. The erythropoietin level in patients with uremic anemia was lower than the level in patients with anemia of other causes but still higher than that of the normal controls. Patients suffering from polycystic kidney disease with or without uremia had a high level of erythropoietin due to local hypoxia of remnant kidney tissue resulting from the pressure of cystic formation. Different methods are used to determine the erythropoietin level, which varies with the stage and etiology of the diseases. There are other stimulating or inhibitory factors of erythropoiesis when the assay is processed. Transfusion and administration of certain drugs also influence the growth of erythroid cells, thus the serum titers of erythropoietin differed markedly between patients at comparable hemoglobin concentration. PMID- 1752157 TI - [A study of Kirby-Bauer method of antimicrobial sensitivity test and resistant plasmid assay with 486 strains of Shigella isolated clinically]. AB - 486 cases of bacillary dysentery admitted to an army hospital during the peak season (July to September) from 1986 to 1988 were studied. The pathogens in 452 cases were tested for antimicrobial sensitivity with 14 kinds of antibiotics by using Kirby-Bauer method recommended by WHO. The results showed that the number of antibiotics to which the dysentery bacteria became resistant had increased. In 1986 the number was 9, while in 1987 and 1988 it increased to 12 and 13 respectively. Among the resistant strains of bacteria, 331 had been assayed for resistant plasmids. 88.8% was positive with more than three resistant plasmids. The result of antimicrobial sensitivity test coincided well with that of resistant plasmid assay. PMID- 1752158 TI - [Determination of neuropeptide Y concentration in the cerebrospinal fluid in patients with cerebrovascular diseases and its significance]. AB - Concentration of neuropeptide Y (NPY) in the cerebrospinal fluid (CSF) of patients with cerebrovascular diseases was measured by using radioimmunoassay. The results showed that NPY concentration in CSF in patients with hemorrhagic cerebrovascular diseases (HCVD) was 4148 +/- 397.2 pg/ml, being significantly higher than the control level of 1083.7 +/- 245.8 pg/ml. While the NPY concentration in CSF of patients with ischemic cerebrovascular diseases (ICVD) was 2214 +/- 289.2 pg/ml, being not significantly different from the level in the control group. The effect of NPY in vasospasm after HCVD was preliminarily discussed. PMID- 1752159 TI - Hair cell regeneration: the identities of progenitor cells, potential triggers and instructive cues. AB - Hair cells are produced and accumulate in the ears of fish and amphibians as they grow during postembryonic life; hair cell regeneration occurs in lateral line organs in those groups and in the cochlea in birds. Continuous time-lapse microscopy has directly demonstrated that supporting cells divide to give rise to hair cells during regeneration in lateral line neuromasts. Supporting cells also appear to give rise to hair cells during regeneration in the avian ear, but additional cell types have been proposed as hair cell progenitors. Alternative interpretations of current evidence are discussed in relation to the possibility that supporting cells may be the common progenitor in all cases of hair cell regeneration. The regenerative proliferation of hair cells in birds occurs in populations of cells that are mitotically quiescent in undamaged ears. Evidence suggests that the extrusion of damaged hair cells and the breaking of intercellular junctional adhesions may be a trigger for regenerative proliferation. The potential triggering influence of phagocytes is also discussed. The differentiation of replacement cells during regeneration in the cochlea may be regulated by surface interactions between cells. A model that could account for the reconstitution of the mosaic pattern of hair cells and supporting cells is proposed. PMID- 1752160 TI - Structural reorganization of hair cells and supporting cells during noise damage, recovery and regeneration in the chick cochlea. AB - Exposure of the chick cochlea to intense acoustic overstimulation leads to rapid changes in the structural organization of hair cells and supporting cells. During the noise exposure the surface areas of the hair cells are reduced and, concomitantly, the adjacent supporting cells expand. If the exposure continues long enough hair cells bleb out apically and are ejected from the sensory epithelium. Surviving hair cells begin to expand their surface areas again within 24 hours after the termination of noise exposure. By 48 hours of recovery most of the hair cells that have died are ejected from the epithelium and new, regenerating hair cells begin to sprout immature stereociliary bundles. The regenerating stereociliary bundles undergo steps in their maturation that are equivalent to those seen during the normal embryonic development of hair cells. The extent and timing of recovery in the chick cochlea correlates with the length of the noise exposure. Shorter exposures (approximately 12 hours) result in only a few regenerating hair cells but the basilar papilla recovers almost completely within 14 days. Longer exposures (approximately 24 hours) lead to the production of more new hair cells but the recovery of the basilar papilla is incomplete, even after 28 days of recovery. PMID- 1752161 TI - Regeneration of lateral line and inner ear vestibular cells. AB - Labelling experiments with [3H]thymidine demonstrate a continuous production of cells in the mechanoreceptive lateral line organs of the eel (Anguilla anguilla) and butterfly fish (Pantodon buchholzi) as well as in the electroreceptive ampullary organ of the transparent catfish (Kryptopterus bicirrhus). Shortly after [3H]thymidine injection many cells are labelled in the middle and basal parts of the sensory organ and after a few days' survival sensory cells are also labelled. The vestibular sensory organs of selected species of fishes, amphibians, reptiles and birds also show a continuous production of cells. In the budgerigar (Melopsittacus undulatus) labelled cells are found in the basal and middle layer of the sensory epithelium a few hours after injection with [3H]thymidine. A few days after the injection labelled cells are found in non calyceal hair cells. After one month the calyceal cells are also labelled. Similar experiments with the bat Pipistrellus nathusii and with normal and gentamicin-treated mice (Mus musculus) show no labelled cells in the inner ear sensory epithelia. The lateral line organs and vestibular epithelia of non mammalian vertebrates all contain a small number of dark cells with the characteristics of apoptotic cells. Macrophages and inclusions in some cells, thought to be remnants of apoptotic cells, are occasionally seen. Fixation at different osmolarities has little effect on the number of dark cells. It is suggested that the continually produced cells replace apoptotic dying cells. PMID- 1752162 TI - Retinal regeneration in teleost fish. AB - The neural retina in teleost fish can regenerate after surgical or neurotoxic destruction. Whereas in amphibians the retina regenerates by transdifferentiation of pigmented retinal epithelial cells, in goldfish (Carassius auratus) the source of regenerated retinal cells is a population of scattered proliferating cells located in the outer nuclear layer within the differentiated retina. These proliferating cells are modified neuroepithelial cells termed 'rod precursors' because in the intact retina they produce only rod photoreceptor cells and do so continuously, inserting new rods into the growing adult retina. Although rod precursors normally exhibit a restricted developmental fate they appear not to be committed to the rod lineage. When retinal neurons are destroyed, rod precursors cease producing rods and give rise to clusters of primitive neuroepithelial cells which divide vigorously and reconstitute the retina in an orderly temporal pattern that mimics the process of normal development. Only after production of cones and other retinal neurons has ceased do rod precursors again appear and resume the generation of rods. We conclude that rod precursors respond to local cues in their environment that regulate the differentiation and choice of cell fate by their progeny. PMID- 1752163 TI - Common mechanisms of retinal regeneration in the larval frog and embryonic chick. AB - Amphibians and embryonic chicks possess the ability to regenerate retinal neurons by the transdifferentiation of pigment epithelium into neuronal progenitors. Recent studies have begun to identify the molecular factors involved in this process. Laminin (a component of the extracellular matrix) has been shown to be important in the process of retinal regeneration in the larval frog both in vitro and in vivo and basic fibroblast growth factor (bFGF) stimulates the same process in chicks in vivo. To determine the mechanisms by which these factors induce retinal regeneration we studied their effects on cultured chick pigment epithelium cells. bFGF was added to enzymically dissociated chick embryo pigment epithelial cells plated at several different densities on various substrates including laminin. We found that bFGF stimulated proliferation but although the cells lost pigmentation and demonstrated distinct morphological changes, no definitive transdifferentiation could be demonstrated using several neuron specific antibodies as markers. When the pigment epithelium was cultured as aggregates on a shaker device which prevented flattening and spreading on the substrate a large number of retinal progenitor cells were generated from the pigment epithelium treated with bFGF. The ability of chick pigment epithelium to undergo transdifferentiation thus appears to be dependent on the physical configuration of the cells. PMID- 1752164 TI - Regenerative capacity of retinal cells and the maintenance of their differentiation. AB - Mechanisms underlying cell type stability and the capacity of retinal cells for transdifferentiation are discussed. It is shown that cells of amphibian pigmented epithelium can be transformed into retina or lens cells depending on the inducing cell type: the influence of retina enables them to be transformed into retina, the influence of lens epithelium, to lens cells (lentoids or lenses). This led to an attempt to discover the molecular character of cell action by means of transfilter induction in early gastrula ectoderm of Xenopus laevis. The results show that the induced cell types correspond to the main inducing cell type, around which a range of neighbouring cell types is produced; this has been shown for five different cell types. The inducing factors involved seem to show qualitative differences. It is probable that they play a stabilizing role in the maintenance of the differentiated state of tissues, since temporary dissociation into cells leads eye tissues to transdifferentiate into other types. Such molecular factors can play a significant role in the maintenance of the type of differentiation and also in conversion into other cell types. These mechanisms of maintenance are not restricted to interactions between molecules and cells, since membranes on the surface of the retina and pigmented epithelium contribute to their shaping and consequently to the stability of the cell type. PMID- 1752165 TI - Regeneration of olfactory receptor cells. AB - The vertebrate olfactory system has become an important model for the study of neural regeneration. The most remarkable feature of this system is its unique capacity for neurogenesis and replacement of degenerating receptor neurons. This replacement is made possible by a persistent neurogenesis among basal cells. Basal cells differentiate, develop into sensory neurons and grow axon processes. Receptor cell axons project back to the olfactory bulb where they reestablish connections with the central nervous system. When mature receptors reach a critical age, are damaged by nerve injury, or are exposed to environmental agents that enter the nasal cavity, they degenerate and are subsequently replaced by newly regenerated receptor cells. Recent experiments demonstrate that olfactory neurogenesis is not simply an extension of growth and development but is a unique capacity for cell replacement that persists beyond maturity and well into old age. Even more remarkable is the finding that replacement receptor cells re establish connections with the CNS and restore sensory function. It is expected that further studies of olfactory neurogenesis using cell and tissue culture methods will provide important advances for the field of neural regeneration. PMID- 1752166 TI - Regulation of neurogenesis and neuronal differentiation in primary and immortalized cells from mouse olfactory epithelium. AB - We have developed an in vitro system for studying molecular events regulating neurogenesis in the mouse olfactory epithelium (OE). Our observations suggest that two types of neuronal precursor may be involved: (1) a transiently existing, immediate neuronal precursor (INP), which generates two postmitotic daughter neurons; and (2) a neuroepithelial stem cell, which may be the basal cell (or some subclass of basal cell) of the OE, and is presumed to be the progenitor of the INP. Using antibody markers that distinguish basal cells and postmitotic receptor neurons in vitro and in vivo, we have shown that neurogenesis occurs early on in OE cultures, but then ceases because INPs divide only once to generate postmitotic neurons and no new INPs are produced by basal cells. To determine whether the basal cell-to-INP transition, or proliferation and neuronal differentiation of the INP, are regulated by crucial growth factors or cellular interactions, we are testing various polypeptide growth factors and extracellular matrix proteins for their effects on OE neurogenesis in vitro. We have also generated immortalized OE cell lines by using retroviruses to transduce oncogenes into cultured OE cells. One such cell line (derived from a primary OE basal cell culture) develops branching processes when transplanted into neonatal mouse brain -a condition in which cells from freshly isolated OE can undergo apparent morphological differentiation into neurons. PMID- 1752167 TI - Rules for the production of sensory cells. AB - During development and regeneration, cells divide, move, change their internal state, respond to environmental signals and die according to rules specified by their genome. These rules of cell behaviour are fundamental to any explanation of how sensory tissues are generated or repaired. An attempt is made to summarize and compare the rules underlying the development of four different sensory tissues: mammalian retina, avian auditory epithelium, mechanosensory bristle fields in Drosophila and, very briefly, Drosophila retina. There are parallels in cell lineage, in the timing of developmental decisions, in the postponement of the choice of differentiated state until the final cell division cycle, in the role of short-range lateral inhibition, and in the involvement of genes such as Notch and achaete/scute. These similarities may reflect the conservation of some basic mechanisms of sensory development that originated early in the evolution of multicellular animals. If so, studies in Drosophila, with its advantages for molecular genetics, may give important clues to the mechanisms of sensory development and regeneration in vertebrates. PMID- 1752168 TI - Neuronal-epithelial interactions in mammalian gustatory epithelium. AB - There are two neurally controlled morphogenetic programmes in the fungiform papillae of the rodent tongue. When gustatory axons are present they not only promote the expression of taste receptor cells but also simultaneously suppress the outgrowth of an ectopic filiform spine. Innervation during development is essential for the initial formation of taste buds. Consequently, denervation during development irreversibly prevents the establishment of a permanent line of stem cells for taste buds, in contrast to the reliable re-emergence of taste buds after the reinnervation of denervated adult gustatory epithelium. Monoclonal antibodies to keratins selectively recognize cells in particular differentiated states and may contribute to an understanding of the cell lineages and cell-cell interactions that lead to taste buds and filiform spines. Regeneration may recapitulate the late steps in taste development but not the early steps, which are slower and subject to irreversible alteration with denervation. Arguments are set forth that the nerve dependence of taste buds and some other cutaneous receptor cells provides an important selective advantage. Nerve dependence ensures that a more protective integumental covering will replace any superficial, secondary sensory cells rendered useless by denervation. PMID- 1752169 TI - Regeneration of electroreceptors in weakly electric fish. AB - Weakly electric teleost fish possess two classes of electroreceptors: tuberous and ampullary organs. Ampullary organs are used for detecting prey, while tuberous organs detect the fish's own electric organ discharges (EODs) and those of conspecifics. EOD frequency varies among individuals within a species and a fish's tuberous receptors are sharply tuned to its own EOD frequency. In young, small fish both tuberous and ampullary afferents innervate only single organs. As fish grow new receptor cells are added to each organ and it divides into two daughter organs. This process continues resulting in numerous organs in a cluster; the afferent nerve innervates all the organs in a cluster. When a patch of skin is removed new skin grows back complete with new receptor organs of both classes. From our studies we have shown that: (1) new organs are found only in the presence of nerve fibres; (2) their morphological development during regeneration is similar to their normal development; (3) organs divide rapidly giving rise to daughter organs until each afferent fibre innervates the correct number of organs for a fish of its size; (4) receptor cells are broadly tuned below the EOD frequency of a given fish and they gradually increase their tuned frequency and sharpness of tuning until they become correctly tuned to that EOD frequency; (5) the correct matching of receptor tuning to EOD frequency occurs in fish in which the spinal cord has been severed or with lesions of the medullary pacemaker nucleus, thereby eliminating the EOD and any possible 'calibration' signal; and (6) basal and capsule cells of receptor organs in the intact skin around the wound divide after skin damage and are a possible source of precursor cells for new receptor organs. PMID- 1752170 TI - The general architecture of sensory neuroepithelia. AB - All neuroepithelia are sheets of cells lining an internal or external surface of the body and resting on a basement membrane. They consist of at least two kinds of cell, receptor cells and sustentacular (supporting) cells. Some contain undifferentiated precursor cells and senescent or degenerating cells. The potential for plasticity and regeneration in different sensory neuroepithelia varies widely according to their origins and structure in any individual animal and according to the species in which they occur. Four sensory neuroepithelia are described as examples of the range of construction, complexity, and life history. PMID- 1752171 TI - Regeneration in epithelial proliferative units as exemplified by small intestinal crypts. AB - Surface epithelia are subdivided structurally into a series of partially autonomous proliferative units. Within each unit the proliferative cells are organized into a lineage or hierarchy each with relatively few ancestral (stem) cells. This structural organization is strikingly illustrated by the gastrointestinal mucosa where the proliferative cells are packaged into crypts. In the mouse small intestine there are 250 cells in total per crypt of which about 150-160 are proliferative. The latter cells are arranged as a series of about 10 rings each of about 16 cells, starting at about the 4th position from the bottom of the crypt and running up to the 13th-14th cell position. The stem cells are believed to be located in the lowermost ring. We have been studying the regenerative process in mouse small intestinal crypts after various levels of injury. Exposure to small doses of cytotoxic agents (e.g. gamma-radiation) reveals that some cells in the stem cell zone are very sensitive but that apparently unaffected cells in the zone are easily disturbed in their cell cycle characteristics by this minor damage. Such observations suggest that some of the controls on stem cell proliferation are extremely local in their action. The stem cells can detect the death of one of their members and the remainder respond accordingly. After more severe injury (drugs or higher doses of radiation) the first detectable changes also appear in the stem cell zone. It is concluded that the crucial cells in the regeneration process in epithelia are the stem cells. The cell kinetic properties during regeneration have been studied experimentally and modelled mathematically. PMID- 1752172 TI - Hair cell regeneration in the avian inner ear. AB - The postembryonic production of hair cells in fish and reptiles has been known for several decades. Until recently it was assumed that this capacity was absent in the more highly specialized inner ears of birds and mammals. Recent research has shown, however, that birds have the capacity to rebuild a damaged inner ear. Summarized here are studies conducted in our laboratory which address the following questions: (1) Which are the precursors of the regenerated hair cells? (2) Are the new hair cells functional? (3) What are the ultrastructural properties of regenerated hair cells? and (4) Can the level of proliferation be regulated? Both the auditory and the vestibular systems of the avian inner ear were studied. Our results provide some answers to these questions. The implications of the results are discussed. PMID- 1752173 TI - [Assessment of Hasegawa's dementia scale for screening and diagnosis of dementia in the elderly]. AB - A sample of 2573 older inhabitants living in Shanghai was investigated on the spot for screening dementia by HDS. Their scale scores on HDS ranged from 3 to 32.5, and the mean score 25.4; according to the 4-grad classification on HDS, 35.3% were classified as normal, 46.3% as borderline, 16.1% as predementia, and 2.3% as definitive of dementia. The assessment by HDS corresponded well with clinical diagnosis of dementia according to DSM-III based on clinical symptoms in 96.3% of 2573 aged. Assessment by HDS was applied to 100 older patients with clinical diagnosis of psychiatric disorders. The scale scores in 76 cases with functional psychiatric disorders and in 24 cases with organic psychosis ranged from 16 to 32.5 and 1 to 28, respectively, and the mean scale score 28.1 and 17.2, respectively. The mean scale score of those with schizophrenia was 29.9, neurosis 30, depression 28.3, SDAT 9.1, MID 15.1, and other dementia 23.6. These results demonstrate that HDS is a practical and valuable tool of assessment for epidemiological, clinical diagnosis and research work to evaluable dementing states of Chinese elderly. PMID- 1752174 TI - [Relation between psychoactive drugs and body weight among inpatients]. AB - A self-control study was conducted among 92 inpatients for the purpose of the establishment of the relationship between psychoactive and body weight, with the latter measured once a week, stepwise regression (alpha = 0.3) revealed: increase or decrease of body weight was associated not only with the kinds of medicines administered, but also with the types of the diseases, living standard, and therapeutic effects. The mechanism of body weight increase was explored and some suggestions were also given with regard to the prevention of the increase of body weight. PMID- 1752175 TI - [A randomized controlled trail of maprotiline treatment of depressive disorder]. AB - In order to evaluate the clinical effects of maprotiline (home made), the authors made a clinical comparison with Ludimil (Cida-Geigy) 96 cases (66 endogenous depression and 30 neurotic depression) meet the CMA diagnostic criteria (1984) were analysed. The patients' symptoms were assessed with HAMD, side effects with TESS. The study group included 72 patients treated with chinese product, the rest cases as control group treated with Ludimil. No significant differences of efficacy in terms of age, sex and duration of symptoms were found in both groups. After the six-week course of Maprotiline treatment, the authors found the dosage, therapeutic effect and adverse reaction in both groups are very similar. It is concluded that the chinese product is safe and effective. PMID- 1752176 TI - [Developments observation of serum thyrohormone level in schizophrenics]. AB - Measure of serum T3, T4, RUR, FT4I was made at admission, sixth weeks after admission and discharged from hospital for 42 cases schizophrenic. T4, FT4I value of sixteen patients was higher than in normal controlled group, but there was no difference between other 26 cases schizophrenic and controlled group. The authors reported that abnormal levels of T4, FT4I in 16 cases patients relate to disease course and severe symptoms and suggested that the change of serum T4, FT4I in some cases was related to the disease in itself. PMID- 1752177 TI - [Serum prolactin response to electroconvulsive therapy in patients with major depression]. AB - Serum prolactin (PRL) levels were determined at 30 min before and 5, 15, 30 and 60 min after the first and sixth electroconvulsive therapy (ECT-1 and ECT-6) in 12 female patients with major depression. There was a significant increase in serum PRL after ECT-1. The mean maximum PRL level was obtained at 30 min after ECT-1 and was 3.18 times of baseline level. The rate between mean maximum PRL level after and baseline before ECT-6 was 1.89 and was significantly lower than that during ECT-1. ECT-6 caused a significantly lower PRL release than did ECT-1 too. The possible mechanisms of produced these results were discussed. PMID- 1752178 TI - [Quantitative EEG analysis and the value for differential diagnosis on depression: I. Spectral power and coherence analysis]. AB - Spectral power and coherence analysis were taken on 47 depressive patients and 43 normal controls. Depressive patients showed abnormal brain activity mostly in frontal-central regions. The endogenous and manic-depressive groups mainly presented higher power of slow activity and predominant in right hemisphere, while the non-endogenous and other groups presented higher power mainly in the fast bands. Coherence analysis showed that the coherence of EEG between homogenous points of two hemispheres was decreased in depressed patients. PMID- 1752179 TI - [Quantitative EEG analysis and the value for differential diagnosis on depression: II. Multivariate regression and discriminate analysis]. AB - Multivariate regression and discriminate analyses were carried out based on the EEG power variables and some related clinical materials from 47 depressed patients and 43 normal controls. The results of regression analysis showed that the severity and duration of depression were associated with EEG slow activity, while the age of first episode and age of the patients were associated with EEG fast activity. Discriminate analysis clearly demonstrates the possible utility of EEG data in the differential diagnosis of depression. PMID- 1752180 TI - [Psychologic correlates in peptic ulcer]. AB - Psychological correlates of peptic ulcer were assessed in a group of volunteer patients whose ulcers were identified by endoscopy. Logistic regression analysis and "t" test indicates that the peptic ulcer patients studied had higher "neuroticism" scores on EPQ, more life events experienced in the year previous to the investigation (on the revised Holmes' Social Readjustment Rating Scale), more severe symptoms on SCL-90, and lower social support scores on the Social Support Rating Scale than matched controls. The most frequently reported SCL-90 symptoms were anxiety, depression, somatization and obsession. The relationship between the occurrence of peptic ulcer and the characteristics of personality, life events, social support and psychological health level is discussed. PMID- 1752181 TI - [Changes of monoamines in the ischemic rat brains with a modified technique of fluorescent histochemistry induced by glyoxylic acid]. AB - A modified technique of fluorescent histochemistry induced by glyoxylic acid was used to study the changes of catecholamine (CA) and 5-hydroxytryptamine (5-HT) in the brains, walls of the brain vessels and the dura mater of the rats at regular intervals after ligation of bilateral common carotid arteries (BCCA). At the same time the effect of chinese herbs, Radix Salviae Miltorrhixae, red flower and Motherwort on CA and 5-HT of these rats was also observed. In the normal rats, yellow fluorescent granules that indicated the presence of 5-HT were found in the walls of the cerebrum, brainstem, cerebellum and dura mater vessels. Green fluorescent fibers that indicated the presence of CA were clearly revealed to follow the walls of vessels of the dura mater, but not those of the brain vessels. After ligation of BCCA, the 5-HT granules of the walls of the brain vessels and the CA fibers of dura mater vessels decreased, but CA fibers occurred in the walls of the brain arteries. The above mentioned changes became more marked following prolonged of ischemia of the brain 24 hours after ligation of BCCA, very few 5-HT granules and CA fibers were found in the walls of the brain and dura mater vessels. It was interesting to see that the increase of CA fibers occurred in the whole muscle layer of the brain arteries. The changes of the monoamines were not so evident in those rats treated with Radix Salviae Miltorrhixae, red flower and motherwort even though they had also ligation of BCCA. PMID- 1752182 TI - [Pathological and clinical features of primary ventricular hemorrhage due to moyamoya disease]. AB - The clinical and pathological features of 20 cases of moyamoya disease complicated with primary intraventricular hemorrhage (PIVH) and verified by CT scanning, cerebral angiography and autopsy were reported. It seemed to the author that moyamoya disease appeared to be prone to cause PIVH, this hemorrhage being likely due to ischemic malacia in the ventricular wall. The tortuous, abnormal network vessels ruptured and bled as a result of infarction and damage of the walls of the miliary aneurysms. PIVH might be divided into two types: the panventricular hemorrhage and partial ventricular hemorrhage, according to the amount of blood that filled into the ventricles. 6 cases of the panventricular type were fatal. The symptoms were in conformity with the traditional concept of the most critical, intraventricular hemorrhage. The external ventricular drainage in combination with lumber puncture drainage would be the better way of treatment for these patients. 14 cases of the partial ventricular hemorrhage type showed the clinical features of acute subarachnoid hemorrhage (SAH). The treatment was similar to SAH too, and the prognosis was much better. It would be worth noting that moyamoya disease should be a factor not to be neglected in causing PIVH. PMID- 1752183 TI - [Continuous observation of the electrocardiogram following experimental cerebral hemorrhage]. AB - An intracranial injection of 5 ml of heparinized autoblood was made into 14 healthy domestic dogs. Model of experimental cerebral hemorrhage was made. 7 dogs of a control group were not injected with the blood. Electrocardiograms (ECG) were recorded before operation, 6 hours after operation and once a day from the first to the seventh day after operation in order to observe the changes of ECG after cerebral hemorrhage. The result indicated that 11 dogs (78.57%) among the dogs of the hemorrhage group had abnormal ECG after operation, but only 2 (28.57%) of the 7 dogs of the control group were so. Comparison between the two groups showed significant difference, P less than 0.01. Abnormal ECG displayed the earliest during the postoperation 6 hours. These abnormal phenomena, mainly obvious in T wave changes and prolongation of the Q-T interval, were transient and began to disappear on the third day. PMID- 1752184 TI - [Electromyographic studies on myotonic dystrophy]. AB - EMG studies were made on 12 cases of myotonic dystrophy (MyD). The EMG of the distal and proximal muscles of the limbs showed no marked difference (P greater than 0.05). The myotonic potentials, pathologic spontaneous potentials and incomplete interference patterns had more marked differences respectively as the durations of the disease were prolonged. PMID- 1752185 TI - [A twin study on the heredity of electroencephalogram]. AB - A human twin study was undertaken to research the heredity of the EEG. The accuracy of the twins zygosity diagnosis was more than 98 per cent. Thirteen pairs of monozygotic twin had an intraclass correlation of 0.43 in alpha frequency and 0.65 in alpha sequence time per minute, and twelve pairs of dizygotic twins had an intraclass correlation of 0.20 and 0.34. Their hereditability was estimated by three methods as 29-58 per cent and 47-66 per cent, respectively. PMID- 1752186 TI - [An analysis of findings EEG and brain CT scans in patients with primary hypoparathyroidism]. AB - 10 cases of primary hypoparathyroidism showed abnormal findings on EEG. Among them 9 cases were also verified by CT scans. It was considered that the severity of abnormalities in primary hypoparathyroidism was not only influenced by the serum concentration of calcium, but also related with the severity and extent of calcification in the brain. These findings would be of significance with regard to the diagnosis, treatment and prognostic evaluation of primary hypoparathyroidism. PMID- 1752187 TI - [A brief account of event-related potentials]. PMID- 1752188 TI - Kinematics of epithelial wound closure in the rabbit cornea. AB - The kinematics of wound closure in the healing rabbit corneal epithelium are modelled. The analysis is able to model the movement of the wound edge on the corneal surface. A unified formalism is described which embeds the surface velocity of the wound margin within the computational algorithm to enable calculation of the surface velocity of the wound margin from the time course of (1) planar wound area, or (2) wound diameter. The procedure can be implemented with the standard least-squares estimation procedure. A polynomial velocity function is discussed, but the model allows for any appropriate velocity function to be used to suit particular conditions of wound closure. Corneal curvature effects are incorporated to avoid the errors associated with a planar representation of wound closure on a curved corneal surface. The approach offers greater flexibility by avoiding the theoretical flaws of previous models which are often limited in scope and nonbiological in nature. PMID- 1752189 TI - The subretinal fluid in retinal detachment. A cytologic study. AB - Following retinal detachment, subretinal fluid (SRF) fills the neoformed space. Subsequently subretinal and preretinal strands of proliferative tissue begin to form. We have collected the subretinal fluid withdrawn during retinal detachment surgery. We have studied subretinal fluid cytologically to evaluate the number and the type of cells present in the fluid, and by means of transmission electron microscopy. The first cell type to be present in the fluid represented degenerated aspects of pigmented epithelial cells (PECs). Successively, other cell types appeared in the fluid as nerve cells (rods, cones and glial cells), macrophages and well preserved pigmented epithelial cells. PMID- 1752190 TI - Reduced severity of oxygen-induced retinopathy in the newborn rat after topical administration of timolol maleate. A preliminary study. AB - The effects of timolol maleate on intraocular pressure (IOP) and the severity of retinopathy induced by exposure to 80% oxygen were studied in newborn Wistar rats. One drop of timolol maleate (0.25%) instilled in each eye twice a day for the first ten days of life substantially reduced intraocular pressure without significantly modifying arterial pressure. Forty percent of the ratlings treated in this way failed to develop oxygen-induced retinopathy (OIR) after exposure to 80% oxygen for the first five days of life; in the other 60% OIR was less severe than that seen in an identically oxygenated group that did not receive timolol. The authors hypothesize that the pharmacologically induced reduction in IOP may have attenuated the effects of the high concentrations of oxygen on the immature retinal vessels by improving the ocular perfusion pressure. The possibility that timolol maleate also exerts a direct action on the caliber of these vessels cannot be excluded. PMID- 1752191 TI - A new diffuse loss index for estimating general glaucomatous visual field depression. AB - Experience with a number of visual fields has shown that the algorithm used earlier for estimating general depression in glaucomatous visual fields was too conservative. A new, more sophisticated algorithm for calculating diffuse loss has been devised and the results obtained in the evaluation of 20 glaucomatous visual fields were compared with those obtained manually. The new algorithm is less restrictive, yet produces values for diffuse loss which agree well with the empirical estimates (R = 0.97, N = 14). The new diffuse loss index is also compared with the mean defect index (R = 0.77, N = 159), the 18th Bebie curve ranked value (R = 0.87, N = 159), and the previous diffuse loss index (R = 0.98, N = 105). A general discussion of various aspects of diffuse loss is included. PMID- 1752192 TI - Carcinoma arising in an odontogenic keratocyst with orbital invasion. AB - A 54-year-old black female presented with proptosis and reduced visual acuity of the left eye. Computerized tomography (CT) revealed tumor involvement of the left cavernous sinus and posterior orbit. The patient had a nineteen year history of a left-sided jaw tumor which recurred despite surgical and radiation therapy. Biopsy demonstrated a parakeratinized odontogenic keratocyst with areas of transformation into an invasive squamous cell carcinoma. Although a parakeratinized odontogenic keratocyst may be locally invasive, to our knowledge, no case of a parakeratinized odontogenic keratocyst involving the orbit or cavernous sinus previously has been reported. PMID- 1752193 TI - Effects of ultraviolet radiation and visible light on hamster pupil. AB - Light does not cause a miotic response in mammals after a topical application of atropine. However, such common sense is based on the pupillary response to visible light. We found ultraviolet (UV) caused slight but evident miosis, even when the patient did not perceive visible light. In order to understand this mechanism further, we conducted in vitro experiments using hamsters. The in vitro hamster iris contracted even when the retina was withdrawn in an incubation solution. The contraction of the hamster pupil caused by visible light was inhibited by procaine, quinacrine, and by the withdrawal of divalent cations, but not by indomethacin, AA861, FPL55712 or autonomic blocking agents. UV-induced miosis was very delayed, continuing after cessation of UV stimuli. Nordihydroguaiaretic acid did not inhibit the miosis induced by UV and/or visible light. The UV-induced miosis was not significantly affected by allopurinol or verapamil, suggesting mechanisms other than neuronal mediation and oxidative stress. This study shows that the isolated hamster iris can react to UV and visible rays. UV-induced miosis is different from the miosis caused by light reflex. To our knowledge, UV-induced miosis has not yet been reported. PMID- 1752194 TI - [Ultrastructural features of a neurotransplant, functionally integrated with the recipient's brain]. PMID- 1752195 TI - [Progesterone concentration in mice at early stages of homo- and heterogeneous pregnancy]. PMID- 1752196 TI - [General and peculiar traits of colchicine and platinum (II) complexes binding with tubulin]. PMID- 1752197 TI - [Peripheral localization of enkephalin-immunoreactive neurons in pteropod molluscs]. PMID- 1752198 TI - Prevalence of substance abuse in a psychiatric evaluation unit. AB - The prevalence of substance abuse and psychiatric illness was studied in a Psychiatric Evaluations Unit. Twenty-six percent of the subjects received a psychiatric diagnosis only with no concomitant substance use disorder. Thirty four percent were diagnosed with a substance use disorder but with no other psychiatric disorders. Thirty-nine percent of the subjects had a history of both psychiatric and substance use disorder; 62% of these substance abusers with a psychiatric illness reported using drugs (including alcohol) the week before the interview; 56% used illicit drugs while 44% used alcohol only. Differences among substance abusers with a psychiatric illness, those with a substance abuse diagnosis alone, and those with a psychiatric diagnosis alone are presented. PMID- 1752199 TI - Evaluation of nefazodone self-administration in rhesus monkeys. AB - Intravenous self-administration of nefazodone, a potential new antidepressant medication, was evaluated using a substitution procedure in rhesus monkeys. Subjects had established stable rates of responding for cocaine (0.033 mg/kg per infusion) under a fixed-ratio 10 schedule during 60-min sessions each day. Various does of nefazodone hydrochloride (0.03-0.3 mg/kg per infusion) were substituted for cocaine for four consecutive daily self-administration sessions. Compared to rates of responding obtained during saline substitutions, nefazodone failed to function as a reinforcer when substituted for cocaine. In only one monkey, at one dose, did the rate of responding exceed the range of saline responding; an effect not observed in two subsequent replications in that subject. In all three monkeys, the total number of infusions tended to decrease during the 4-day nefazodone substitution and the majority of nefazodone infusions occurred during the first quarter of each session, with few infusions occurring in the latter three-quarters. Overall intake of nefazodone increased as a function of dose per infusion. Such a result is expected when response rates do not vary with dose, which is more likely to occur when a test drug is not a reinforcer. In summary, the present results provide no evidence of reinforcing effects with nefazodone and suggest that it would possess little or no abuse liability. PMID- 1752200 TI - Comparison between observer assessment and self rating of withdrawal distress during opiate detoxification. AB - The Subjective Opiate Withdrawal Questionnaire (SOWQ) and the Objective Opiate Withdrawal Scale (OOWS) were administered to detect withdrawal distress during a rapid opiate detoxification. No correlations could be observed between the clinical assessments and self ratings of the 20 patients participating in this study. The observers' ratings of withdrawal reached pre-treatment levels within 3 days. In subjective rating, withdrawal distress returned to normal levels 120 h after detoxification. We conclude, that self reports are as important as observer ratings in assessing treatment efficacy. The use of both scales might prevent early relapse after detoxification. PMID- 1752201 TI - Scottish cocaine users: wealthy snorters or delinquent smokers? AB - Ninety-two cocaine users were interviewed in Scotland. Most were middle-class nasal users, also used other drugs and generally gave cocaine a positive rating. One half of them had at some time used cocaine more than once a week. For some, this period lasted some months, when as much as 30 'lines' of cocaine were used per day of cocaine use. More of these heavy users reported adverse effects of cocaine than was the case for light users. Nonetheless, most heavy users had reduced their use by themselves to the point that their current cocaine use was no different from that of light users. Possible explanations for this apparently spontaneous reduction are discussed. PMID- 1752202 TI - Effects of ethanol on phospholipid acylation in rat erythrocytes: a model for a biochemical approach to membrane adaptation. AB - Challenging intact erythrocytes from naive rats with ethanol resulted in dose dependent decreases in rates of acylation of phosphatidylcholine and phosphatidylethanolamine. In erythrocytes from ethanol-treated animals, the responses were of lesser magnitude, indicating a lower sensitivity to ethanol. This relative resistance, typical of the state of tolerance, was not associated with increased baseline rates of acylation of PC and PE, nor with changes in fatty acid specificity of acylation reactions. Taken together, the data suggest that (1) intact rat erythrocytes represent a reliable and easily reproducible model for studying biochemical correlates of the adaptive response to ethanol; (2) phospholipid acylation reactions are implicated in the initial sensitivity and subsequent acquisition of tolerance to ethanol in membrane erythrocytes; (3) on the basis of the measured acylation reactions, rat erythrocytes appear to develop tolerance, but not dependence, to ethanol. PMID- 1752203 TI - The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. AB - There appears to be increasing evidence that ethanol toxicity may be associated with an increased production of reactive oxygen intermediates. In rats we studied the effect of 4 weeks of ethanol ingestion on the liver cytosolic defense system against active oxygen species. Compared with the control rats, the ethanol-fed animals had a significantly higher liver malondialdehyde content and significantly lower reduced glutathione level. Moreover, ethanol feeding resulted in a decrease of superoxide dismutase and catalase activities while glutathione peroxidase activity was only slightly diminished. Thus, prolonged ethanol administration profoundly modified the hepatic status of the enzymatic defense system leading to lipid peroxidation that may disrupt vital functions of liver cells. PMID- 1752204 TI - [Computer-assisted determination of the pharmacokinetic parameters of Solupront after intrauterine administration in cattle]. AB - The drug "Solupront" a sulfonamide was clinical tested in healthy heifers and cows with endometritis, retentio secundinarum etc. The test-results were evaluated with the computer-program "Phakimo". The pharmacokinetic parameters show that there are similar relationships between the extravasal and the intravasal application of this osmochemotherapeutic. A retard of absorption is shown in dioestrus and in prooestrus. If there are pathological signs in uterus, the rate of absorption of the drug is higher and the excretion via urine is more quickly, too. The effect of the sulfonamide in the drug "Solupront" is impaired after application in the uterus in order of the quick absorption, of distribution and excretion and also in order of dilution by lochia and by interaction with p aminobenzoic acid. PMID- 1752205 TI - [Preliminary studies of the content of lead, cadmium and arsenic in feed, cattle and food of animal origin from different production regions of Saxony]. AB - The modern industrial and agricultural production provides many contact points for the food animals with several toxic substances. After their ingestion by the way of feed or water they may endanger the human health as residues or environmental contaminants in food of animal origin. Currently meat, milk and eggs produced on farms in the new federal states of Germany are considered to be dangerous with respect to their xenobiotic burden by numerous consumers. The own trials have been made to give first information about lead, cadmium and arsenic concentrations in feedstuffs, meat and milk from different dairy farms in Saxonia. No serious problems could be detected referring to the metal contents in roughage, grain and crops. Only a few feed samples reached eg. exceeded the permissible upper limits for arsenic and cadmium. But none of the examined feedstuffs contained inadmissible lead concentration. Milk and muscle produced in a metal polluted and not polluted areas were very low in cadmium, lead and arsenic. Total different is the situation in the cases of liver and kidney. Both organs of cows held on farms near a smelter were rich in cadmium and lead. The cadmium concentration in liver and kidney often and the lead concentration sometimes exceeded the permissible upper limits for food. In this context cadmium in kidney of older cows seems to be a problem in general. The results of the own examinations give no information about differences in the mean metal burden of feed and food between new and old federal states of Germany.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752206 TI - [Interrelationships between methylmercury exposure and selenium supplementation in cockerels using selected laboratory diagnostic parameters and toxicological parameters of residues]. AB - A feed loading experiment was applied in 2 phases to 45 young cocks over 12 weeks, using 1,2-N,N-bis(methylmercury)-p-toluolsulphamide-dressed wheat (50% of base ration). Investigations were conducted to study the effects of selenium supplementation (0,2 mg Se as sodium selenite/l drinking water) on biochemical and hematological parameters (calcium, phosphorus, total protein, albumin, creatinine, urea, activity of alkaline phosphatase, hematocrit, hemoglobin, leucocyte count) as well as on parameters relating to toxicological residues (selenium and mercury levels in liver, musculature and kidneys). Statistically secured differences were found to exist between the experimental groups with regard to selenium and mercury in the liver and mercury concentrations in kidneys. Possible interrelationships were discussed. PMID- 1752207 TI - [Circadian rhythm of the toxicokinetics and toxicodynamics of the plant protection substance dinitro-ortho-cresol in rabbits]. AB - Results from chronotoxicological investigations with the plant protection chemical DNOC has been described and judged. It has been studied hyperthermia caused by i.v. application of 7.5 mg/kg body weight on rabbits to 6 different times, starting at 4 a.m. with 4-hours-intervals as well as the dose-effect relation in each case with 3 doses to the time of application at 12 a.m., 6 p.m., 12 p.m. and 6 a.m. and the renal DNOC excretion after a dose of 10 mg/kg body weight. There was found a time dependent rhythm in all experiments. Acrophase of hyperthermia is placed in the middle of the phase of activity of the animals at 12 p.m., however it depends on the dose. The results are showing, that the position of acrophase by constant environmental factor is neither a substance specific nor an animal specific constant. PMID- 1752208 TI - [The occurrence and metabolism of physiologically normal-appearing hydrocarbons in agricultural animals]. AB - Carbohydrates are determined in food from animals as result of contamination. Therefore they are a risk for the consumer and may impair the quality of the products. There are differences in the pattern of residues between the groups of carbohydrates. Especially the saturated carbohydrates indicate heavy differences. Aromatic carbohydrates have an equalized level. These relationships are examined by tests with n-alkane-yeasts-feeding of pigs. PMID- 1752209 TI - Prophylactic and therapeutic application of Propionibacterium avidum KP-40 in swine and calves with acute enzootic bronchopneumonia. AB - The usefulness of the prophylactic or therapeutic application of Propionibacterium avidum KP-40, a potent stimulator of the monocyte-macrophage system, was demonstrated in piglets and calves. After a 3-month-period of observation PA-treated piglets showed a significantly improved development (decreased number of infections, gain of body weight). In piglets and calves the therapeutic use of PA together with oxytetracycline proved to be superior in the treatment of acute endemic enzootic bronchopneumonia (AEB) as compared to groups of animals receiving PA or oxytetracycline alone. PMID- 1752210 TI - [Review article: factors influencing the estrogen and progesterone concentration in the blood of cows in late pregnancy]. AB - This review describes the factors influencing the estrogen und progesterone levels in late pregnant cows. The various endogenous and exogenous factors (breed, calf birth weight, sex of calf, number of fetuses, season, nutrition and stressors) influence particularly significant estrogen and progesterone concentrations in peripheral blood and may lead to high variations of hormone values between cows. The possible mechanisms of influence on the estrogen und progesterone levels are discussed. PMID- 1752211 TI - [The concentration of ascorbic acid in different tissues of calf fetuses in 3 different development stages]. AB - The concentration of ascorbic acid in the cerebrum and in the brain stem of bovine fetuses decreased with increasing body weight; in the cerebellum there was no change. The decrease of the concentration in the lungs, in the heart, in the kidneys, in the M. longissimus and in the M. semimembranosus in the course of the fetal growth was different. In the liver and in the adrenals the concentration in the 3 groups of fetuses with a body weight of 4.18 +/- 2.01, of 9.72 +/- 0.97 and of 17.12 +/- 2.61 kg was similar. The highest concentrations were found in the adrenals, in the testes and in the cerebrum. The functional significance of the changes in the concentration in the tissues of the bovine fetuses is discussed and compared with the results in human fetuses and in adult cattle. PMID- 1752212 TI - [A method for the treatment of oviduct obstruction in cattle using CO2 insufflation into the uterus]. AB - The investigations were carried out on 59 cows from Holstein half-breed, establishing that 8 cows suffered salpinx obstruction (5 cases with unilateral obstruction and 3 cases with bilateral obstruction). The authors are using an apparatus made by themselves, for insufflation of air in the obstructed uterus, and which is useful in desobstruction treatment, too. For diagnosis, CO2 was introduced inside of uterus. The authors used for treatment PBS (saline phosphate buffer) in addition with penicillin G, hydrocortisone and trypsin. Before air insufflation in uterus there will be infused 10-20 ml 2% Lidocaton. The cows must be examined in oestrus period, or 2 days after PGF2 alfa administration. The gas must be introduced under rectal palpation, and pressure must not be higher than 500 mm H2O column. If there is a permeable oviduct, after 15-20 sec. from gas introduction, ist is possible to palpate the filled oviduct. From ovary we can perceive a rustle produced by gas crossing in abdominal cavity. In case of salpinx obstruction, the treatment must be start as soon as possible. The utilized liquid for treatment will be introduce by gas pressure, inside of uterus and oviducts. Using this method, it managed the repermeability of oviducts at 3 from 8 treated cows. In each case, there were used 3 treatments at 48 h interval. After the second insemination (I.A.) 2 cows remained pregnant. PMID- 1752213 TI - The influence of colostral leukocytes on the immune system of the neonatal calf. IV. Effects on bactericidity, complement and interferon; synopsis. AB - The influence of colostral leukocytes on the bactericidity of whole blood of calves against a strain of E. coli and on the activities of haemolytic complement and interferon-alpha (the antiviral activity of sera resisting an acidic treatment at pH 2 for 6 h) in the serum was investigated during a period of 4 weeks using 4 experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. The bactericidity of whole blood of the COL+ group was significantly higher on the second and third days of life while the activity of haemolytic complement was lower after the first week as compared to the COL- group. No interferon-alpha was detectable in the sera of both COL groups. The bactericidity of the MS groups was significantly lower than that of the COL groups after the first day of life. It was significantly lower in the MS+ group after one week of life while the activity of haemolytic complement was higher than that of the MS- group. Three out of 5 MS- and only one out of 7 MS+ calves had low titres of interferon-alpha in their sera on the third day. Three out of 6 MS- calves died and 5 out of 7 MS+ animals. The mean day of death was 4.0 in the MS- and 8.4 in the MS+ group. Based on the in vitro results of this and the previous three communications it can be concluded that leukocytes which are an integral part of normal bovine colostrum, influence immunological reactions of the calf and that they may enhance its defence against infection. Colostral leukocytes in the absence of humoral components of the colostrum are not able to prevent fatal losses in the calves due to natural infection, although their influence on immune responses of the calves was detectable in vitro. PMID- 1752214 TI - The female brindled mouse as a model of Menkes' disease: the relationship of fur pattern to behavioral and neurochemical abnormalities. AB - The brindled mottled mutant mouse, a model of Menkes' disease, has alterations in copper homeostasis which cause, among other sequelae, neuronal degeneration in selected areas of brain. This work examined the neurochemical changes at postnatal days (PND) 15, 30 and 60 in females heterozygous for the sex-linked brindled mutation. These data were compared to behavioral alterations and to fur coat color at these same time points. The brindled heterozygotic females had lower concentrations of norepinephrine (NE) in the cingulate cortex, and higher levels of dopamine or dopamine metabolites in the cingulate cortex, thalamus and hypothalamus across all ages, although the difference was greatest at PND 15. The brindled females were much less active than their normal littermates at PND 15, but the differences were no longer evident at PND 30 and 60. Mottling of the fur is believed to result from low tyrosinase activity caused by abnormalities in copper metabolism. The fur pattern and behavior of the brindled mice were highly correlated with NE levels in the cingulate cortex and thalamus. These data show that female brindled mice have neurochemical abnormalities similar to (if less severe than) the male hemizygotes, that these abnormalities are regionally specific, are most apparent prior to 30 days of age, and are linked to behavioral deficits. These data also show that the extent of such deficits can be predicted by a quantitative analysis of the fur pattern of these females. PMID- 1752215 TI - Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. AB - Microglia and astrocytes undergo proliferative and differentiative changes in vivo after trauma or diseases such as multiple sclerosis (MS). Oligodendrocytes are destroyed in lesions in MS. Interleukin-1 (IL1) and tumor necrosis factor alpha (TNF alpha) are involved in inflammation of the central nervous system and are elevated in MS. We have investigated the changes in cell morphology and cell number induced by IL1 and TNF alpha in purified and mixed populations of primary rat brain microglia, astrocytes, oligodendrocytes, and glial precursors. Depending on the target population, proliferation, differentiation, or inhibition of cultured cells was observed. The data also suggest that interactions among cell populations occur and support the hypothesis that IL1 and TNF alpha effects may be indirect, possibly through induction of other factors. PMID- 1752216 TI - Neuronal lysosome accumulation in degrading synapses of sensory-motor and limbic subsystems in the duck Anas platyrhynchos: indication of rearrangements during avian brain development? AB - Brains of developing duck embryos and ducklings were analysed daily by light microscopy after complete serial brain sectioning and lysosome staining (Gallyas technique), providing insight into synaptic degradation and degeneration during short periods of synaptogenesis. Both regional and temporal shifting pattern of lysosome accumulation (LA) in degraded synapses were detected in sensory-motor pathways during the course of development. LA occurred in sensory projections of embryos, and proceeded from forebrain sensory fields toward limbic regions and finally motor projections. LA disappeared from these structures at the age of 4-6 weeks. LA was analysed ultrastructurally in selected sensory, limbic and motor regions indicating that lysosomes selectively accumulated in transient synapses, leaving parts of either pre- or postsynaptic elements untouched. In no case did denervated neurons exhibit any signs of cell death. Apparently, the LA phenomenon seems critical in terms of both irreversible elimination and remodelling of persisting synapses. Thus, neuronal rearrangement mediated by lysosomal degradation, i.e. degeneration of synaptic components, is supposed to be an integral constituent of synaptogenesis during adaptive processes in sensory-motor systems. These results are discussed with regard to developing brain functions during behavioural adaptation of this precocious bird. PMID- 1752217 TI - Cosmetics and their adverse effects. PMID- 1752218 TI - Acute poisoning from hair dye. AB - A series of 18 cases of acute hair dye (paraphenylenediamine) poisoning were reported. The characteristic features of swollen face and the chocolate brown colour of the urine were diagnostic. Asphyxia was found to be the major early challenge of life. Tracheostomy and intensive medical treatment with hydrocortisone and chlorpheniramine maleate (antihistaminic drug) and penicillin cover were life saving in all serious cases. The mild cases were successfully treated with hydrocortisone and chlorpheniramine maleate and penicillin without tracheostomy. The dye was detected in the urine by thin layer chromatography on silica gel and proved to be paraphenylenediamine. Early prompt diagnosis and clinical management proved to be life saving in both serious or mild hair dye poisoning. PMID- 1752219 TI - Haematocrit levels and anaemia in Ethiopian children. AB - The paucity of data on the haematological profile of Ethiopian children prompted this survey. In October and November, 1987, a survey of haematocrit levels utilizing capillary blood and morphological studies on blood films by means of the Wright stain was conducted in the peri-urban community of Koladiba in Northwestern Ethiopia. All but 21 children (0.5-6 years) in the community participated. The mean and median haematocrit levels in children 0.5-6 years was 38% each with a range of 26-52%. Lowest haematocrit was found between 1-2 years of age. The 3rd and 97th percentile values were 31-45% and identical with the mean +/- 2 S.D. values. On a third of the children (251), blood film studies were done and 20% had microcytic hypochromic red blood cells. When an altitude corrected cut-off point of 38% was employed to define anaemia, the prevalence rate was 47.2%, the highest rate (60%) in children 1-2 years. However, use of a cut-off point based on the third percentile or +/- 2 SD (31%), resulted in an underestimation of anaemia rates by 40%. The findings of this study are consistent with previous reports on anaemia rates and haematocrit levels in Ethiopian children residing in a similar environment. Although the iron content of the Ethiopian diet is one of the highest in the world, nutritional anaemia is a public health problem. Intervention measures using iron supplementation and nutrition education through existing primary health care network are recommended. PMID- 1752220 TI - Effect on sodium sulphate on the adsorption of chloroquine and mefloquine to activated charcoal. AB - The effect of an added saline cathartic (Sodium sulphate) on the in vitro adsorption of chloroquine and mefloquine by activated charcoal were determined. Chloroquine phosphate at 125, 250 and 500 micrograms/ml had 10.0, 23.0 and 38.4 percent adsorption to 50 mg charcoal. When the concentration of activated charcoal was increased from 50 to 200 mg, there was no significant difference in the amount of chloroquine adsorbed. The amount of mefloquine (400-1000 ng/ml) adsorbed ranged from 60.62 to 95.8 percent. The common saline purgatives sodium sulphate at 7.5 mg/ml increased the B-50 for chloroquine slightly from 376 to 444 mg whereas it has little or no effect on the adsorption of mefloquine to activated charcoal. PMID- 1752221 TI - Long distance truck-drivers: 1. Prevalence of sexually transmitted diseases (STDs). AB - A cross section study was conducted among long distance truck drivers to determine the prevalence of sexually transmitted diseases (STDs) and antibodies to human immunodeficiency virus (HIV). A total of 8 drivers and their assistants en route from port of Mombasa to countries in East and Central Africa were enrolled into the study. Blood was taken for HIV and syphilis serology. Discharges from urethra and genital ulcer disease (GUD) were cultured. Seroprevalence for HIV was 18% and 4.6% for syphilis. Fifty percent of Neisseria Gonorrhea cultured were penicillinase producers. Most of the men with urethral discharge and all the GUD were culture negative, probably due to prior treatment. Lack of circumcision, past history of GUD and urethritis were significantly associated with HIV seroconversion. PMID- 1752222 TI - Rupture of the gravid uterus: a review. AB - A total of 105 patients were treated for ruptured gravid uteri at the Kenyatta National Hospital, Nairobi, Kenya, over a five year period, January, 1984 to December, 1988. During the same period, there were 44,156 deliveries, giving an incidence of uterine rupture of 1:425 deliveries. Of these, records for 95 patients were traced and analysed, and the results are presented here. Majority (61.0%) of these patients were aged less than 30 years, and 62.1% were gravida 5 or less. 54 (56.8%) of them had rupture of scarred uteri, 33 (34.7%) had spontaneous rupture, while 8 (8.4%) had traumatic rupture. 56 (59.0%) ruptured while at the Kenyatta National Hospital. Repair of the uterus without tubal ligation was the treatment offered to most of them, while total abdominal hysterectomy was rarely done. The perinatal case fatality rate was 60% and there were two maternal deaths giving a maternal case fatality rate of 2.1%. Factors associated with uterine rupture at the Kenyatta National Hospital are discussed, and possible ways of reducing the incidence suggested. PMID- 1752223 TI - Vascular access for haemodialysis. AB - In a fifteen month period (August 1987 to November 1988) forty patients requiring haemodialysis had 83 angioaccess procedures performed. Arteriovenous (AV) shunts and arteriovenous fistulae were the commonest procedures, comprising 56 (67%) and 20 (24%) of the patients respectively. Subclavian catheters and artificial grafts were used less frequently. Nephrologists and senior house officers attached to the Renal Unit were responsible for fashioning A-V shunts and inserting subclavian catheters while the A-V fistulae were fashioned by the urologists and vascular surgeons. The commonest complication of A-V shunts were clotting, occurring in 31 (55.4%) followed by bleeding in 14 (25%). Eight (32%) of the A-V fistulae never functioned from the beginning. It is noted that we are still very dependent on A-V shunts for vascular access in end stage renal disease (ESRF) patients and this is associated with an unacceptable level of complications. This dependency on A-V shunts in ESRD patients should be stopped or phased out. A-V fistulae should be used more frequently. Their constructions should be well thought out, executed and supervised by the few surgeons who are versed in them together with their follow-ups. PMID- 1752224 TI - Screening for dementia in elderly Nigerians: results of the pilot test of a new instrument. AB - We developed a new instrument for the assessment of cognitive functions in elderly Nigerians as a preliminary step towards the determination of the burden of dementia in Nigerian Communities. The instrument was pilot tested on 250 cognitively-normal Nigerians and their scores compared with those of 15 subjects with clinically-diagnosed dementia. The cognitively normal subjects had a mean score of 24 (SD 2.3) while the cognitively-impaired subjects had a mean of 35 (SD 3.0) and p less than 0.01). Of those with normal cognition, subjects with at least 6 years of education had significantly lower mean scores than illiterates (p less than 0.005). The instrument was completed in 4 minutes in normal subjects as against 7 minutes in those with cognitive impairment. The 19 item instrument had a sensitivity of 80% and a specificity of 72% at a cut-off value of 27. With the elimination of 3 items related to information, the sensitivity and specificity increased to 93% and 83% respectively. We conclude that the 16 item version is adequate for a 2 stage study of dementia in this environment, its main role being that of screening in the first stage. PMID- 1752225 TI - Vaginal and cervical abnormalities associated with trichomonal infection. AB - Cytological changes were studied among 393 women, reporting to Samir Health Centre, Khartoum (Sudan), using Papanicolaou staining. Vaginal trichomoniasis was confirmed by wet-mounts and cultural methods. Non-specific inflammatory changes were prominent (17.4%). In 33.5% of parasitised patients, the cervix was found healthy. Cancer of the cervix was not detected in patients investigated. PMID- 1752226 TI - Urinary stone disease in Dar es Salaam. AB - Forty four adult patients, 34 males and 10 females, with urinary stones were seen over a six-month-period at Muhimbili Medical Centre, Dar es Salaam. Most patients were peasants and semiskilled workers. 8 of the patients were Arabs, which suggests a high predisposition for this race. 12 of the patients had a history of having suffered from bilharzia. There was a high proportion of bladder (and urethral) stones (30%) but upper urinary tract stones were still predominant (70%). Of 20 patients whose stones were available for analysis, 8 were composed of calcium oxalate, 7 of calcium phosphate and 5 of mixed composition. The ratio of stone patients to all hospital admissions of 243 per 100,000 suggests the prevalence of urinary stone disease is comparable to that found in Western countries. PMID- 1752227 TI - Carotid angiography in Nigeria: a review. AB - Five hundred and seventy-five patients subjected to carotid cerebral angiography at the University of Nigeria Teaching Hospital, Enugu, over a period of five years are presented. The commonest indication for the study consisted of clinical suspicions of tumour, trauma and vascular problems. In cases of subacute or late sequelae of head trauma, cerebral angiography prove to be an important neuro investigative tool especially in institutions where CT scan is not available. Despite the invasive nature of cerebral angiography, the low incidence of side effects encountered in this procedure, the ease of the technique and the general non-availability of the more advanced non-invasive neuro-diagnostic aids and the relative low cost implications are strong enough factors and reasons which have encouraged us to advocate the use of the technique in developing countries. Nevertheless, because the reported complications are mostly related to the expertise of the investigator the occasional investigator must be discouraged. PMID- 1752228 TI - Outcome of pregnancy in nephrotic syndrome: a report on five cases. AB - In a 6 year period (1984-1989) we have had the opportunity to take care of five patients who had nephrotic syndrome and became pregnant. Four of them had mesangial proliferative glomerulonephritis while one had focal segmental glomerulosclerosis. Four of the pregnancies went to term while one was terminated at 34 weeks gestation because of deteriorating renal function in the mother. All the pregnancies ended in delivery of normal babies. However, two patients have since died of end stage renal disease, while the remaining three continue to be nephrotic with reduced levels of renal function following the deliveries. PMID- 1752229 TI - Depressed erythropoietic activity of Nigerian pregnant women. AB - Reticulocytes production index was determined in 63 pregnant women and in 96 patients. The results show that 86% of the pregnant women, who were registering their pregnancy for the first time, were anaemic. There was significant reticulocytopenia in all the anaemic pregnant women and in the patients. Erythropoiesis was found to be depressed in all subjects patients by two to seven times those expected in normal responsive bone marrows. There was no correlation of the bone marrow impairment with parity of the pregnancy. The bone marrow impairment was more pronounced during the 16th week of gestation and less so in older pregnancies. Malnutrition and infection (especially malaria) are suggested as the aetiological factors of the bone marrow depression of erythropoiesis. PMID- 1752230 TI - Timing of surgery in acute cholecystitis. AB - Eighty-one cases of cholecystectomy performed over a period of 12 months were reviewed. Those operated upon acutely, those operated upon electively, and those initially treated in the hospital before surgery was performed were compared with regards to the length of hospital stay, injury to the common bile duct, wound infection and mortality rate. There is no significant difference in the mortality rate, but the rate of wound infection 23%, and injury to the common bile duct (17.95%) are highest in those operated upon acutely. It would seem as if the "delayed" surgery, that is, conservative treatment for about a week to two in the hospital before surgery, is preferred if common bile duct exploration or a choledocho-enterostomy is anticipated. PMID- 1752231 TI - Formation of 6 beta-hydroxydexamethasone from dexamethasone by A6 cells. AB - A6 cells, a continuous cell line derived from kidney of Xenopus laevis, were incubated with [3H]-dexamethasone for 24 h. When radioactive compounds in media were separated by reversed phase high pressure liquid chromatography, two radioactive fractions were found. The less polar fraction which contained 91-93% of total radioactivity cochromatographed with dexamethasone, whereas the polar fraction contained 5% of total radioactivity in media. In order to rigorously identify the polar metabolite, large scale cultures were carried out and the polar compound was separated and purified by reversed phase high pressure liquid chromatography. The purified material was analyzed by secondary ion mass spectrometry and nuclear magnetic resonance spectroscopy. By these procedures, this material was identified as 6 beta-hydroxydexamethasone. To our knowledge these are the first data indicating that dexamethasone can be metabolized by transporting epithelia such as A6 cells. PMID- 1752232 TI - Effect of dietary calcium on serum BGP (osteocalcin). AB - The present study was designed to clarify the effects of dietary calcium (Ca) intake on serum BGP (osteocalcin) levels. Twelve women with a mean age of 21.2 years participated in the study. After one week of normal Ca intake (mean +/- SE, 535 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for one further week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. Serum total and ionized Ca concentrations as well as BGP, PTH and 1,25(OH)2D3 were measured at the end of each period. Amounts of Ca and hydroxyproline excreted in urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in either group. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. Serum levels of BGP and 1,25(OH)2D3 were significantly augmented along with a transient increase in urinary hydroxyproline excretion after Ca deprivation. These results suggest that serum BGP is increased after one week of Ca restriction in healthy subjects. PMID- 1752233 TI - Maturation of the pituitary-thyroid axis during the perinatal period. AB - To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week. PMID- 1752234 TI - Suckling stimulates the expression of vasoactive intestinal polypeptide gene in rats. AB - The effect of suckling on vasoactive intestinal polypeptide (VIP) gene expression in the hypothalami was studied during the postpartum period in rats. Female rats were divided into two groups immediately after delivery. In one group, a mother was housed with 8 pups, and in the other, without any pups. The former group was named S(+) and the latter S(-). On days 0, 3, 6, 9 and 12 after delivery, the mothers were killed by decapitation. Hypothalamic VIP mRNA was measured by RNA dot hybridization. Although the VIP mRNA level showed no significant change after delivery in the S(-) group, VIP mRNA in the S(+) group on days 6, 9 and 12 increased to 1.6, 3.5 and 2.1 times higher than the level observed on day 0, respectively. These results suggest that suckling induces the synthesis of VIP after 6 postpartum days. PMID- 1752235 TI - Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. AB - The pharmacokinetics of total and free prednisolone (PSL) in six healthy men, with or without pretreatment with oral glycyrrhizin (GL), was investigated to confirm whether oral administration of GL influences the metabolism of PSL in man. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS) with or without pretreatment with 50 mg of oral GL four times. Blood samples were taken from a peripheral vein at 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after the start of PSL-HS infusion. The concentrations of total PSL in plasma were analyzed by high performance liquid chromatography, and the free PSL was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of PSL were determined by non-compartment analysis. Oral administration of GL was found to significantly increase the concentrations of total PSL at 6, 8 h, and of free PSL at 4, 6 and 8 h after PSL-HS infusion. Moreover, oral administration of GL was also found to modify the pharmacokinetics of both total and free PSL. After oral administration of GL, the area under the curve (AUC) was significantly increased, the total plasma clearance (CL) was significantly decreased, and the mean residence time (MRT) was significantly prolonged. However, the volume of distribution (Vdss) showed no evident change. This suggests that oral administration of GL increases the plasma PSL concentrations and influences its pharmacokinetics by inhibiting its metabolism, but not by affecting its distribution. PMID- 1752236 TI - Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) regulation of insulin receptor function: phosphorylation of insulin receptor with A kinase decreases the insulin binding activity. AB - The effect of phosphorylation of insulin receptor with adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase. [125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase. These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3',5'-cyclic monophosphate regulate the insulin binding to the alpha subunit through phosphorylation of the beta subunit of insulin receptor. PMID- 1752237 TI - Paradoxical prolactin response to growth hormone-releasing hormone in a patient with hyperprolactinemia and empty sella. AB - In a 30-year-old woman with amenorrhea due to hyperprolactinemia, serum PRL increased to twice the basal amount in response to growth hormone-releasing hormone (GHRH). Roentgenological studies revealed no pituitary adenoma but empty sella. Bromocriptine therapy normalized serum PRL and made the paradoxical response to GHRH disappear. The paradoxical response did not occur in any of eight other patients with hyperprolactinemia due to prolactinoma. Although this case is rare, GHRH stimulates PRL as well as GH release remarkably in some cases with hyperprolactinemia without a GH-producing tumor. PMID- 1752238 TI - Silent thyroiditis in an eleven-year-old girl, associated with transient increase in serum IgM and thyroid hormone. AB - An 11-year-old-girl with silent thyroiditis associated with a transient increase in serum IgM and thyroid hormone is described. The levels of serum IgM decreased from 4.38 g/L to 3.35 g/L after 1.5 months at the same time as thyroid hormones returned to normal. An unidentified antecedent infection or exposure to antigen causing the increase in serum IgM might have triggered the occurrence of silent thyroiditis in this patient, although a search for viral antibodies revealed no significant titer changes during the course of the disease. PMID- 1752239 TI - The electrophoretic properties of a DNA cube and its substructure catenanes. AB - Electrophoretic properties have been measured for a DNA molecule whose helix axes have the connectivity of a cube. This molecule is a topologically bonded complex of six cyclic 80-mer molecules, in which each cycle corresponds to a face of the cube. Each cyclic molecule is doubly catenated to each of its four neighbors. Substructures of this molecule include a 5-cycle structure lacking one strand, two topoisomers of 4-cycle structures and two topoisomers of 3-cycle structures. One 4-cycle structure is a cyclic belt around the cube, lacking a top and a bottom, whereas the other lacks two catenated strands, such as the top and the front. One 3-cycle structure is a linear belt of three cycles, and the other corresponds to the three cycles that surround a corner. Each of these molecules is separable from the others under appropriate gel conditions. We have measured mobilities and calculated Ferguson plots for each of these molecules on polyacrylamide gels under both native and denaturing conditions. The measurements have been made with 1.25, 2.5, and 5% crosslinking of the gels. The data show that the higher-symmetry 3-cycle and 4-cycle structures migrate more slowly than their lower-symmetry isomers, under conditions where their Ferguson plots are parallel. PMID- 1752240 TI - Estimation of polyacrylamide gel pore size from Ferguson plots of linear DNA fragments. II. Comparison of gels with different crosslinker concentrations, added agarose and added linear polyacrylamide. AB - The mobilities of various DNA fragments in two normally migrating molecular weight ladders were studied in polyacrylamide gels containing different concentrations of the crosslinker N,N'-methylenebisacrylamide (Bis). The acrylamide concentration ranged from 2.5-10.5%T (w/v); the Bis concentration ranged from 0.5-10%C (w/w), with respect to total acrylamide. Ferguson plots were constructed for each of the DNA fragments in gels of each composition. The Ferguson plots of the different multimers in each molecular weight ladder were nearly parallel in gels containing 0.5-3%C, converged close to a common intercept at zero gel concentration in gels containing 4%C, and crossed at approximately 1.5%T in gels containing 5 and 10%C. If the mobilities observed for the different DNA fragments at zero gel concentration were also extrapolated to zero DNA molecular weight, a common limiting mobility was observed in gels of all crosslinker concentrations. This limiting mobility was approximately equal to the free solution mobility of DNA. The effective pore radius of each gel was estimated from Ferguson plots based on relative mobilities, using the mobility of the smallest DNA fragment in each molecular weight ladder as the reference mobility. The calculated gel pore radii ranged from 142 nm to 19 nm, respectively, for gels containing 4.6%T, 1.5%C, and 10.5%T, 5 or 10%C. These pore radii are an order of magnitude larger than previously accepted values, but are consistent with scanning electron microscope measurements (Ruchel, R., et al., J. Chromatogr. 1978, 42, 77-90).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752241 TI - Electrophoretic size separations in liquified agarose of polystyrene particles and circular DNA. AB - Polystyrene sulfate particles of 0.37 to 1.78 mu in diameter are retarded in their electrophoretic migration in proportion to the concentration of agarose liquified above its gelling temperature. In the concentration range of 0.02 to 0.2% liquified agarose, the degree of this retardation in electrophoresis at 40 degrees C is inversely related to particle size. By contrast, mitochondrial DNA (16 kb), plasmid pBR322 DNA (4 kb) and plasmid PSA509 DNA (3 kb) exhibit under the same conditions a degree of retardation which is proportional to their size. This confirms the existence of two divergent mechanisms of size separation similarly observed in other liquid polymer media, i.e. one based on collisions with the gel fiber (molecular sieving) and one based on exclusion from the fiber network (the electrophoretic equivalent of gel permeation). PMID- 1752242 TI - Analysis of limiting factors of DNA band separation by a DNA sequencer using fluorescence detection. AB - The factors affecting the electrophoretic separation of DNA bands in DNA base sequencing using fluorescence detection are analyzed. All the factors contributing to DNA band spacing and band width are evaluated; DNA diffusion and thermal effects on gels are the main considerations. The dependence of the gel's electrical resistivity on gel temperature and the variation of temperature over gel thickness are associated with a broadening of DNA band width. As a result of the analyses the maximum separable base number is represented as a function of various electrophoretic variables. The best separations are possible with an electric field strength corresponding to gel thickness. The maximum separable base number increases as the gel thickness decreases. It also increases as the migration distance increases, but it becomes saturated and has an upper limit when the migration distance is long. This upper limit increases as gel thickness decreases. DNA fragments with 600 and 601 bases can be completely separated from each other under optimum conditions for a 0.2 mm thick gel plate. Furthermore, using the band spacing information, under the same conditions, 750 bases could be assigned separately. PMID- 1752243 TI - Isoelectric membrane simulator: a computational approach for isoelectric immobiline membranes. AB - Isoelectric membrane simulator (IMS) is a computer program meant for computation of pH, buffering power (beta), ionic strength (I) and dissociation degree (a) of a mixture of up to 3 buffering and 1 titrant Immobilines, for generating in a reproducible manner isoelectric membranes. Such membranes, of precise isoelectric point, are then used for large-scale protein purification by isoelectric focusing in multicompartment electrolyzers. IMS can be used, in a more general application, for titrating mixtures of buffers to a desired pH value. This versatile program is written in M.Q.BASIC rel. 2.5 and it runs on any IBM hardware or compatible machine supported by MS-DOS. An example of purification of superoxide dismutase in a multicompartment electrolyzer with a set of fixed pI membranes of widely differing composition is shown. PMID- 1752244 TI - Electrophoresis with intermittent scanning of the migration path: detection of resolution within shortened time. AB - Intermittent optical scanning (by detection of optical density or fluorescence) of the electrophoretic migration path was applied to the resolution of two dyes under an arbitrary set of conditions. Scanning at 5-min intervals allows for detection of resolution between the two zones at least 3 times faster than conventional automatic zone detection employing a detector at the end of the migration path. This result promises that replacing stationary by mobile detectors in general would result in a substantial time saving for automated detection of electrophoretic zones. PMID- 1752245 TI - Use of a fast protein electrophoretic purification procedure for N-terminal sequence analysis to identify S-locus related proteins in stigmas of Brassica oleracea. AB - In the cruciferous plant Brassica oleracea L. (cabbage), the S-locus specific glycoproteins (SLSGs) isolated only in stigmas are considered to play an important role in the normal prevention of self-fertilization. Recent molecular data have shown that the gene encoding these glycoproteins (the SLG gene) belonged to a multigenic family consisting of about 10 homologous copies among which another member is expressed, the S-locus related gene (SLR1gene). Our aim was to determine whether the SLR1-gene proteins were expressed in the stigmatic tissues. We first identified the putative SLSGs or SLR1-proteins by Con A peroxidase detection of glycoproteins separated after isoelectric focusing in polyacrylamide gels. We describe a fast purification procedure for the glycoproteins of interest, based on analytical isoelectric focusing, electrophoresis, and electroblotting of proteins onto polyvinylidene difluoride membranes. Blotted proteins were sequenced for N-terminal amino acid determination. By comparison of the N-terminal sequences of the purified proteins with the peptide sequence predicted from the SLR1-cDNA, we demonstrate the expression of SLR1-like proteins in stigmas of B. oleracea. PMID- 1752246 TI - Temperature-dependent spot positional variability in two-dimensional polypeptide patterns. AB - The effect of temperature, at which isoelectric focusing with immobilized pH gradients is performed, on spot positions and pattern quality in two-dimensional (2-D) electrophoresis was examined. Increased temperatures revealed improved 2-D patterns with respect to sample entry, resolution, and background staining. Focusing at 20 degrees C was superior to focusing at 10 and 15 degrees C. Even at 30 degrees C, a pattern of well-resolved polypeptide spots with a minimum amount of horizontal streaking at the basic end was observed. A computer-based analysis showed that a substantial proportion of polypeptides assumed altered positions in the 2-D pattern in relation to temperature. Mobility shifts of polypeptides were more variable on the neutral part than on the acidic or basic end. The mobility shifts were not restricted to one direction for all the spots whose migration was altered. However, for any given spot, the direction was the same with subsequent increments of temperature. The results clearly demonstrate that a defined temperature for first-dimensional isoelectric focusing is a requirement for the reproducibility of 2-D electrophoresis. After elimination of the cathodic drift, a major source of variability in 2-D patterns, associated with carrier ampholytes, temperature control becomes a critical parameter. PMID- 1752247 TI - Comparison of 14C-amino acid mixture and [35S]methionine labeling of cellular proteins from mouse fibroblast C3H10T1/2 cells by two-dimensional gel electrophoresis. AB - Total cellular proteins from mouse C3H10T1/2 fibroblasts were compared by two dimensional (2-D) gel electrophoresis after radiolabeling with [35S]methionine (35S-Met) or 14C-amino acids (14C-AA). 35S-Met labeling of protein was three to four times greater than 14C-AA incorporation over a 24 h period. Automated comparative analysis of replicate fluorographs after 6, 12, and 24 h of labeling showed considerable homology between radiolabeling methods. More than 88% percent of 35S-Met and 14C-AA-labeled proteins were common at each time point. However, the total number of 35S-Met-labeled proteins dropped from 6 to 24 h while the number of 14C-AA-labeled proteins increased. Additionally, twenty-one proteins were uniquely labeled by 14C-AA that were not detectable by 35S-Met over the labeling period. Densitometric analysis showed that several 35S-Met and 14C-AA labeled proteins exhibited time-related differences in radiolabel incorporation while most proteins remained relatively constant. Protein patterns of silver stained gels from 6 to 24 h were highly registered and showed few qualitative differences. Proteins detected in radiolabeled gels were generally, but not always, found in silver-stained gels. Thus, 35S-Met appears better suited for short-term radiolabeling of cellular protein while more comprehensive labeling of protein occurs with 14C-AA during prolonged incubation of cell cultures under present experimental conditions. PMID- 1752248 TI - Genetic polymorphisms of the A and B subunits of human coagulation factor XIII in mainland Italy and Sardinia: description of a new FXIIIA variant allele. AB - The distribution of the two alleles of FXIIIA and the three alleles of FXIIIB were studied in populations from mainland Italy and from Sardinia. The frequencies of the FXIIIA*2 allele were 0.266 and 0.265. The frequencies of FXIIIB*1 were 0.787 and 0.765; of B*2, 0.070 and 0.094; of B*3, 0.143 and 0.141. A new cathodal FXIIIA allele (A*7) was described in the Rome sample. No significant difference in the distribution of allele frequencies for either system was found between the two populations studied. For typing both markers, good results were also obtained by using whole blood instead of plasma. PMID- 1752249 TI - The characterization and use of different antibodies against the hsp70 major heat shock protein family for the development of an immunoassay. AB - The hsp70 family of major stress proteins is composed of several different members exhibiting similar structural and functional properties. In order to obtain an antiserum with wide epitope reactivity, rabbits were immunized with a mixture of native and denatured hsp70 purified from bovine muscle by ATP-affinity chromatography. Screening for antibody specificity was performed by a "sandwich" enzyme linked immunosorbent assay (ELISA). Immunoprecipitation and immunoblotting analyses demonstrated that the polyclonal antiserum obtained by us and a monoclonal antibody raised against a different preparation of antigen recognized the same determinant on the native hsp70 molecule (inducible form). With a different specificity the polyclonal antiserum recognized only the denatured monomers of the other members of the hsp70 family. These results are discussed in relation to the immunological features of the hsp70 molecule and to the development of an immunoassay for the detection of hsp70 in cell and tissue extracts. PMID- 1752250 TI - A modified method of genomic DNA preparation in agarose inserts for pulse field gel electrophoresis. AB - According to standard protocol, DNA in agarose inserts is prepared by first embedding the cell in agarose. This is then incubated in the required enzyme (lysozyme, lysostaphin, or zymolase) depending on the cell type (bacterial or plants), for spheroplast formation. Subsequent treatment of the spheroplast with proteinase K allows the isolation of large genomic DNA in agarose suitable for pulse field gel electrophoresis. An efficient and rapid method of preparation of spheroplast is described. In this method a low concentration of enzyme required for spheroplast formation was added before embedding the cell in agarose, which facilitated the digestion of cell wall by the enzyme and allowed use of a low amount of enzyme. Digestion of DNA in agarose inserts prepared by this method, with rare cutting restriction enzyme and pulse field gel electrophoresis, showed that the quality of DNA was as good as obtained by the standard method. PMID- 1752251 TI - High resolution scanning of DNA autoradiographs. AB - The sizes of DNA fragments (alleles) on autoradiographs are measured by means of a computerised video scanner developed in this laboratory. This report investigates the advantages of using higher resolution equipment for this purpose. High resolution is simulated by using existing equipment and moving the video camera closer to the autoradiograph. Test autoradiographs, used to validate the original scanner, have been rescanned to determine the degree of improvement that could be obtained using expensive high resolution equipment. PMID- 1752252 TI - Improved method for identification of proteins using two-dimensional electrophoresis with immobilized pH gradient isoelectric focusing. AB - Recent advances in protein sequence analysis now permit the determination of partial N-terminal and internal primary structure from low picomole quantities of protein. The major remaining hurdles to sequence analysis of small amounts of protein are the identification, isolation, and handling of microgram and submicrogram quantities of protein. The technique of two-dimensional electrophoresis using immobilized pH gradient isoelectric focusing circumvents many of these problems. However, poor correlation between the first and second dimension have prevented use of this technique for the identification of some proteins which can only be assayed prior to the denaturing conditions used in the second dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis procedure. An improved method is presented which allows correlation of the native biological activity (first dimension) to a silver stained protein (second dimension) with a high degree of confidence. PMID- 1752253 TI - A simplified method of protein electroblotting after isoelectric focusing on an ultrathin polyacrylamide gel layer fixed on a cellophane support. AB - A method is described for isoelectric focusing of proteins, using an ultrathin layer polyacrylamide gel on cellophane, followed by electrophoretic transfer of separated proteins onto a nitrocellulose membrane. The polyacrylamide gel is firmly attached to the cellophane and thus protected from mechanical damage; such gels are easily manipulated. Cellophane is permeable to ions and application of this gel support overcomes difficulties resulting from the removal of ultrathin gels from a plastic support on electroblotting. Proteins separated under nondenaturing conditions were transferred onto a nitrocellulose membrane and detected by the concanavalin A-peroxidase technique. The proposed approach makes it possible to analyze the variability of nondenatured proteins and glycoproteins of different origin. PMID- 1752254 TI - Detection of proteins after immunoblotting on nitrocellulose using fluorescent antibodies. AB - A Western blot method is described utilizing 5-dimethylaminonaphthalene-1 sulfonyl (dansyl chloride)-conjugated antibodies to detect proteins transferred onto nitrocellulose. Four proteins of different molecular weight, including human albumin, gamma heavy chain, kappa and lambda light chains of immunoglobulins, were tested. Labeling with the fluorochrome was compared with the method of enzyme-conjugated antibodies and was found to have similar sensitivity, specificity, and safety. Moreover, this method is less expensive, and the labeled antibodies can be prepared fresh in a short time and are free from the disadvantages of enzyme label whose activity is affected by the presence of activators or inhibitors in the tested specimens. PMID- 1752255 TI - Increased selectivity in the detection of glycoproteins on nitrocellulose membranes by washing with sodium hydroxide solution. AB - We increased selectivity in the detection of glycoproteins on nitrocellulose membranes by introducing a washing step using sodium hydroxide solution. Glycoproteins on the nitrocellulose membrane were first oxidized by sodium periodate; biotin hydrazide was then coupled to the aldehyde groups generated in the sugar moiety of the glycoproteins. The membrane was washed twice using sodium hydroxide solution, and avidin-horseradish peroxidase was then coupled to the remaining biotin. This system allows the detection of nanograms of glycoproteins on nitrocellulose membranes, and its specificity allows the clear distinction of glycoproteins from the nonglycosylated protein of bovine serum albumin. PMID- 1752256 TI - Dodecyl maltoside detergent improves resolution of hepatic membrane proteins in two-dimensional gels. AB - This report describes the incorporation of an alkyl maltoside detergent in two dimensional polyacrylamide gel electrophoresis (2-D PAGE) sample lysis buffer in order to improve resolution of protein patterns separated by nonequilibrium pH gradient electrophoresis. Membrane-associated proteins with alkaline isoelectric points form horizontal streaks on two-dimensional electrophoretograms when solubilized with conventional nonionic detergent. Dodecyl maltoside enhances protein delipidation during solubilization and improves pattern resolution and protein mobility. PMID- 1752257 TI - Estimating imprecision of radioassays and related procedures: some considerations. PMID- 1752258 TI - Gallium scintigraphy in Hansen's disease. AB - Gallium 67 imaging was used in 12 patients with documented Hansen's disease undergoing treatment or not, in an attempt to determine the pattern of the disease. Diagnosis was confirmed by histopathology in all patients. The Mitsuda reaction was seen in all patients. Specific nuclear studies were performed when needed to evaluate particular organs better. Gallium 67 images show homogeneous, diffuse and moderate accumulation over the entire skin surface (except for the face) of untreated patients with multibacillary disease. The facial skin in these cases presented homogeneous, diffuse but very marked uptake of gallium. Internal organ involvement was variable. There was a very good correlation among clinical, scintigraphic, immunological and histopathological data. The pattern of the body skin ("skin outlining") and facial skin ("beard distribution") may be distinct for untreated patients with multibacillary leprosy. PMID- 1752259 TI - Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis. AB - Previous studies led us to hypothesize that a fatty acid analogue, 15-p iodophenyl-beta-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14C IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201Tl and 14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14C-IMPPA and necrotic foci size. Distributions of 14C IMPPA and 201Tl in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased 14C-IMPPA uptake were nearly the same (100% +/- 5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70% +/- 5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. PMID- 1752260 TI - Ventricular function during the acute rejection of heterotopic transplanted heart: gated blood-pool studies. AB - Twenty patients who had undergone a heterotopic heart transplant were studied prospectively to determine the relationship between rejection and ventricular dysfunction assessed from gated blood-pool studies. A fully automated method for detecting ventricular edges was implemented; its success rate for the grafted left and right ventricles was 94% and 77%, respectively. The parameters, peak ejection and filling rates, were calculated pixel per pixel using a two-harmonic Fourier algorithm and then averaged over the ventricular region of interest. Peak filling and ejection rates were closely related with the severity of the rejection, while the left ventricular ejection fraction was not. Peak filling rates of both ventricles were the indices closely related to the presence of moderate rejection. Despite the low number of patients, these data suggested that gated blood-pool-derived indices of ventricular function are associated with ventricular dysfunction resulting from myocarditis rejection. Radionuclide ventriculography provides parametric data which are accurate and reliable for the diagnosis of rejection. PMID- 1752261 TI - Measurement of blood flow from first-pass radionuclide angiography: influence of bolus volume. AB - Fractionation of cardiac output on first-pass radionuclide angiography is a recently described technique for measuring blood flow. In order to determine the influence of bolus volume, splenic blood flow (SBF) and renal blood flow (RBF) were measured from widely differing bolus volumes given in sequence over a period of a few minutes in patients undergoing routine bone scintigraphy with technetium 99m methylene diphosphonate. A bolus volume of 0.5 ml, followed by 20 ml of rapidly delivered saline "chaser", was regarded as a "gold standard" bolus. A 50 ml bolus, but not a 20 ml bolus, resulted in a significant underestimation of both SBF and RBF. Thus, using a left ventricular region of interest to generate an arterial first-pass time-activity curve, RBF from a 50 ml bolus was 58% (SEM 4%) that given by a 0.5 ml bolus, while RBF for a 20 ml bolus was 98% (8%). Corresponding values for SBF were 52% (10%) and 102% (12%). A quality control adjustment did not correct the underestimation given by the 50 ml bolus. Bolus volumes greater than 20 ml give unreliable estimates of organ blood flow by this technique. PMID- 1752262 TI - Clinical role of indium-111 antimyosin imaging. AB - Myocyte necrosis occurs in ischaemic, inflammatory and toxic heart diseases and can be detected by indium-111 antimyosin imaging. This allows a non-invasive evaluation of the site, extent and quantitation of the severity of myocardial necrosis. Simultaneous imaging of perfusion in patients with myocardial infarction allows the differentiation of necrosed and perfused areas and the varying degrees of mismatch and overlap, which has prognostic significance. 111In antimyosin imaging is useful in the assessment of patients with unstable angina and in those for whom the diagnosis of infarction or unstable angina is not clear. In suspected myocarditis, a positive scan indicates the necessity for endomyocardial biopsy to confirm inflammation, whereas a negative scan makes the diagnosis of myocarditis unlikely. Antimyosin imaging is not useful as a marker of rejection in the 1 year post-transplant, but uptake after this period is associated with an increased rejection rate and is therefore an important tool in planning management strategies. Most patients on anthracycline treatment have demonstrable uptake, which is related to the cumulative dose and to the ejection fraction. Its role in this situation is as yet unclear. The use of new ligands and radioisotopes (99mTc) is likely to allow earlier imaging and produce improved quality. PMID- 1752263 TI - Positive gallium-67 citrate scintigraphy in Wiskott-Aldrich syndrome with malignant lymphoma. AB - This case describes the first detection of solid lymphoma lesions by gallium-67 scintigraphy in a 12-year-old patient with Wiskott-Aldrich syndrome. Gallium 67 uptake was found in multiple sites in the patient who had developed an undifferentiated small, non-cleaved cell lymphoma. Response to chemotherapeutic treatment is correlated with findings on the gallium scintigraphy follow-up. PMID- 1752264 TI - Effect of implanted epidural stimulator on lower urinary tract function in spinal cord-injured patients. AB - A spinal cord stimulator was implanted in the epidural space in 33 spinal-cord injured patients for the treatment of severe extremity spasticity. We prospectively evaluated the effect of the stimulator on the lower urinary tract in these patients. Urodynamic evaluation was performed preoperatively, and in 23 patients 3 months to 1 year after implantation. Postoperative changes in the lower urinary tract function were noted in 6 patients. One patient converted from detrusor areflexia to detrusor hyperreflexia, and 1 patient converted from detrusor hyperreflexia to detrusor areflexia. Four patients demonstrated changes in the duration of detrusor contraction and external sphincter dyssynergia. In 2 of these 4 patients, the changes in the duration of detrusor contraction and external sphincter dyssynergia were related to the activation and deactivation of the stimulator. Urodynamic parameters did not change significantly following implantation in the remaining 17 patients. We conclude that epidural stimulator implanted for the treatment of spasticity may alter the lower urinary tract function. Patients with postoperative changes in the lower tract function should be evaluated with the stimulator activated and deactivated. PMID- 1752265 TI - Modified surgical technique to correct congenital and acquired penile curvature. AB - We treated 37 patients with severe congenital or acquired penile curvature with a modified Essed-Schroeder corporoplasty without excision of the tunica albuginea. After penile straightening, 34 of the 37 patients (91.9%) were able to resume normal coitus and 29 (78.4%) had excellent results, cosmetic and sexual. Postoperative progression of Peyronie's disease and shortening of the erect penis were rare. In 4 patients, partial necrosis of penile shaft skin or of the prepuce complicated the postoperative course, but there were no long-term sequelae in any case. In patients with concomitant preoperative erectile dysfunction, the dysfunction did not improve after corporoplasty; such patients should be treated primarily with a penile implant. We recommend the modified Essed-Schroeder corporoplasty as a safe and simple method to correct penile curvature. PMID- 1752266 TI - Localized amyloidosis of the urinary bladder. AB - Localized amyloidosis of the urinary bladder is a rare condition. Five patients, 1 with localized secondary amyloidosis, are described. The symptoms, macroscopic hematuria and tumor-like appearance in cystoscopy, may mimic bladder cancer. Diagnosis is based on histopathological examinations with Congo red staining. In most instances, the treatment of choice is transurethral resection and electrocoagulation. Because of the risk of recurrences, a close follow-up is recommended. PMID- 1752267 TI - Efficacy and safety of clean intermittent catheterization in adults. AB - A prospective study was carried out on the efficacy and safety of clean intermittent catheterization (CIC). The series included 41 adults (15 females, 26 males), the mean follow-up time being 40 months. Most patients were suffering from neurogenic bladder disorders. All of them used a self-lubricating hydrophilic catheter. Thirty-one patients (76%) continued to undergo CIC, but 9 discontinued. Thirty patients (73%) experienced bacteriuria during the procedure. Three males had epididymitis. Contrary to many earlier reports, urinary tract infections seem to increase after CIC, raising the question of whether prophylactic antibiotic therapy should be used more often in these cases. There were no urethral complications suggesting that the self-lubricating hydrophilic catheters may be less traumatic than those used previously. PMID- 1752268 TI - ESWL as the treatment for lithiasis in horseshoe kidney. AB - Thirteen patients with lithiasis and horseshoe kidney were evaluated (4 cases with bilateral stones). Fifteen kidney units were treated with extracorporeal shock wave lithotripsy (ESWL), and in 2 cases, percutaneous nephrolithotomy (PCN) was used. The excellent results achieved with ESWL (80%) and the low incidence of complications (2 cases of nephritic colics and 1 case of acute pyelonephritis), lead us to propose ESWL as the therapy of choice for lithiasis in patients with horseshoe kidneys. PCN alone or in association with ESWL would be used in cases with large lithiasic masses. Conventional surgery would only be indicated in those cases which due to their high degree of complexity or difficult endourological access prevent the use of the above-mentioned techniques. PMID- 1752269 TI - Agenesis of seminal vesicles in infertile males: ultrasonic diagnosis. AB - We present the incidence of seminal vesicle agenesis and its association with deferens ductus agenesis in 141 males presenting with infertility. Transrectal ultrasonography was performed in every patient. Ten presented seminal vesicle agenesis (8 unilateral and 2 bilateral). Three had absence of the vas deferens on physical examination (3 of 7 with unilateral seminal vesicle agenesis and 1 of 2 with bilateral). Computed tomography confirmed the ultrasound findings. We emphasize the importance of the anomalies as a cause of infertility and the association with other genitourinary anomalies. Moreover, we state the necessity of transrectal ultrasound in the diagnosis. PMID- 1752270 TI - Vesical tumors in patients under 25 years of age. AB - Behavior of transitional cell carcinoma of the bladder during the third decade of life remains a controversial subject. During the period 1980-1988, we treated 7 patients (4 male and 3 female), 25 years of age or less (mean age 19.3, range 14 25), with transitional cell carcinoma of the bladder. Until now, all patients are alive and without disease during 12-50 months after surgery. In 6 of the 7 patients, endoscopic resection was the choice treatment for superficial stage A/O. The seventh patient underwent a partial cystectomy for a B1 Jewet stage cell carcinoma. We conclude that transitional cell carcinoma of the bladder in patients under 25 years of age has a less aggressive biological behavior. Therefore, ultrasonographic examinations and serial urine cytology represent the elective test for follow-up. Cystoscopy would only be performed in doubtful cases. PMID- 1752271 TI - Recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract. AB - A retrospective analysis of 53 patients with an upper urinary tract (UUT) transitional cell carcinoma, which was treated surgically, was performed in relation to the development of a subsequent bladder tumor. In 19 of the 53 patients (35.8%) bladder tumors developed following surgery of a UUT tumor. The simultaneous occurrence of a bladder tumor and more than two tumors in the UUT had a significant influence on the rate of bladder tumor recurrence. On the other hand, location, mode of growth, grade, stage and vascular invasion of the UUT tumor, and history of bladder tumors did not seem to be related to the frequency of subsequent bladder tumors. These findings suggest that the diversity of UUT tumors at the time of diagnosis is an important factor in bladder tumor recurrence. Therefore, clinical and pathological examinations should be carefully performed in patients with UUT tumors. PMID- 1752272 TI - Early diagnosis and treatment of spinal dysraphism to prevent urinary incontinence. AB - Spinal dysraphism represents a very rare congenital anomaly of the spinal cord and cauda equina, often associated with cutaneous sacral lesions. This condition results in distorsion of neural tissue, possibly leading to vesical dysfunction and urinary incontinence. A series of 12 children with spinal dysraphism (4 lipomeningoceles with tethered cord, 3 tight filum terminale, 2 dermal sinuses, 2 arachnoid cysts, 1 anterior meningocele) observed during the last 6 years is presented. The patients are divided into two groups: group A includes 5 infants (age range 4 months-2 years) and group B 7 older children (4-12 years). All 7 patients of group B were referred for urinary incontinence as their chief complaint; only 1 had evidence of a skin lesion while 3 had a club foot. In group A, 4 had skin lesions (2 asymptomatic and 2 dermal sinuses referred after several episodes of meningitis) and the 5th child had a club foot. The diagnosis was made by myelo-CT scan in the earlier 4 and by magnetic resonance imaging in the more recent 8 cases. All 12 children were operated. In group B, the patients' urinary incontinence persisted but did not worsen (3 were stable and 4 had slightly improved); in group A, 2 were dry (follow-up greater than 2 years), 1 could not be accurately evaluated because he was less than 2 years of age, and the 2 who suffered from meningitis were incontinent. Early diagnosis and neurosurgical treatment of spinal dysraphism may prevent urinary incontinence. Accurate urodynamic, neurophysiologic, and neuroradiologic evaluation of children with severe voiding anomalies or club foot is recommended even if no lumbosacral cutaneous lesions are present. PMID- 1752273 TI - Pericavernous prosthetic band for erectile dysfunction in venogenic impotence. A new surgical technique. AB - A series of 35 patients who were treated surgically by pericavernoplasty using a prosthetic band is presented. At the 1-year follow-up visit, 57% still had improved erectile capability. At the present time, it is difficult to determine whether or not surgical treatment will result in failure. However, according to recent histological studies, prognostic insight in the future might be provided through the analysis of erectile tissue, but for the present moderation must be used in deciding upon surgical treatment since there is a lack of precise physiopathologic understanding of erectile dysfunction. PMID- 1752274 TI - Stone fragility--measurement of stone mineral content by dual photon absorptiometry. AB - We measured the mineral content of urinary tract stones by dual photon absorptiometry, which is widely used for the analysis of bone mineral content, and compared the values of the stones by dual photon absorptiometry (DPA values) with the results of an in vitro fracture study as well as those of an in vivo extracorporeal shock wave lithotripsy treatment study. The results of a preliminary experiment showed that the DPA values of 20 urinary tract stones reflected actual stone mineral content. As a result of the in vitro fracture study, the DPA value calculated by volume of a struvite stone, which was the most easily disintegrated, was the lowest (0.53 g/cm3). The DPA values of calcium oxalate monohydrate and apatite stones, which poorly disintegrated, were the highest (0.98, 1.01 g/cm3). The DPA value of calcium oxalate dihydrate, which moderately disintegrated, was 0.86 g/cm3. By the in vivo extracorporeal shock wave lithotripsy treatment study, the total DPA values of stones measured before extracorporeal shock wave lithotripsy treatment in 12 patients were 0.73 +/- 0.34 g in successful cases and 1.92 +/- 0.43 g in unsuccessful cases with a significant difference between the two (p less than 0.05). These results showed that the measurement of stone mineral content by dual photon absorptiometry was useful in predicting the fragility of stones against shock waves before performing extracorporeal shock wave lithotripsy treatment for patients with urinary tract stones. PMID- 1752275 TI - Anatomy of the venous drainage of the human testis: testicular vein cast, microdissection and radiographic demonstration. A new anatomical concept. AB - The venous drainage of the testis was identified and described in an autopsy, radiographic and operative series of 30, 28 and 7 adult males, respectively. Testicular vein cast--right and left--was prepared in autopsy specimens to identify the course, tributaries and communications of the testicular vein. Intraoperative spermatic venography was done in 17 men with and in 11 men without varicocele. The retrograde spermatic venography showed the precise anatomy of the pampiniform plexus. Antegrade spermatic venography was done to identify the valves. During cystectomy in 7 adult men, the whole tree of the spermatic vein was taken and microdissected. Our findings show that the venous drainage of the testis cannot be looked upon as it is in the standard anatomy; on the contrary, it deviates from the description in the text. We demonstrated that the venous drainage of the testis is via the pampiniform plexus, which is primarily drained by the testicular and external pudendal veins. The testicular vein--midway between the internal inguinal ring and the lower pole of the kidney--divides into the medial and lateral branch to form a delta. The medial branch communicates with the ureteral and contralateral veins; there, it terminates in the left renal vein or inferior vena cava on the right side. The lateral branch communicates with colonic and renal capsular veins and terminates in the perinephric space. There is no cross-communication between the left and right testicular venous systems in the scrotal, retropubic or pelvic areas. The only cross-communication is in the abdomen, and is seen in only 50% of men. The testicular vein has no valves. PMID- 1752276 TI - Angiosarcoma of the bladder: a case report with regard to histologic and immunohistochemical findings. AB - Bladder angiosarcoma is an extremely rare neoplasia whose aggressive biological behavior follows that of other angiosarcomas. The second case of primary angiosarcoma of the bladder is reported pointing out the immunohistochemical characteristics of these neoplasias. Using immunoperoxidase staining techniques, Ulex lectin has proved to be a more sensitive marker for endothelial cells than factor VIII-related antigen, and it should be used as an additional marker for endothelial cell-derived tumors. PMID- 1752277 TI - Bilateral seminal vesicle abscesses. AB - We report a case of a seminal vesicle abscess successfully treated by percutaneous perineal drainage. Magnetic resonance imaging was helpful in clarifying the differential diagnosis. Seminal vesicle abscess is a rare pathological entity; since 1958, only 7 cases have been reported in the literature. Because of its nonspecific clinical symptoms, clinical diagnosis is often ambiguous. An overview of the literature, as well as a discussion of the diagnosis and the treatment of the seminal vesicle abscess will be presented. PMID- 1752278 TI - Renal cell carcinoma: late recurrence in 2 cases. AB - We present 2 patients with late recurrence 16 and 11 years after nephrectomy for renal cell carcinoma. Metastases were solitary and their location very uncommon (vastus externo muscle and colon). In the reviewed series of 5,758 patients with renal cell carcinoma only a temporal muscle metastasis and another in the colon were observed but none of them was solitary. PMID- 1752279 TI - Treatment of carcinoma in situ of the urethra with intraurethral instillations of bacillus Calmette-Guerin. Case report and review of literature. AB - We present the case of a 60-year-old man with carcinoma in situ of the urethra after previous successful radiotherapy of an invasive bladder tumor. Intraurethral instillations with bacillus Calmette-Guerin were given. In spite of initial success, recurrences developed after two courses of 12 intraurethral instillations, and radical surgery was performed. The use of bacillus Calmette Guerin is reviewed with regard to the locations of superficial transitional cell carcinoma outside the bladder cavity. PMID- 1752280 TI - Methotrexate, vinblastine, adriamycin and cisplatin versus methotrexate and cisplatin in advanced urothelial cancer. A randomized study. AB - From September 1984 to December 1988, 28 consecutive patients with metastatic urothelial cancer entered a randomized study to compare 4 courses of modified methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) to 4 courses of methotrexate followed by folinic acid rescue and cisplatin (MP). Non-responders or relapsing patients were to be crossed to the other therapy. Hematological toxicity was more frequent (85%), but less severe, in patients treated with M-VAC than in patients treated with MP (21%, with 1 septic death). Complete plus partial remissions were achieved in 10 (71.4%) of 14 patients treated with M-VAC and in 6 (50%) of the 12 evaluable patients treated with MP. The 20% difference lay only on complete remissions, which were 8.3% in the MP versus 28.5% in the M VAC group. At cross-over, however, only 1 of 5 patients resistant to MP responded to M-VAC, while 3 of 5 patients resistant to M-VAC responded to MP. It seems that M-VAC should be considered as the first-line therapy of choice in metastatic urothelial cancer, while MP, or high-dose methotrexate, could be considered for salvage. PMID- 1752281 TI - Value of bladder wash cytology in the follow-up of patients with bladder carcinoma receiving intravesical chemoprophylaxis with mitomycin C. AB - 511 bladder wash cytologic findings in 121 patients receiving intravesical chemoprophylaxis with mitomycin C after transurethral resection of stage pTa to stage pT2 bladder carcinoma were retrospectively analyzed. In 42 recurrent tumors, sensitivity of detection by cytology amounted to 67% in GIII tumors, 56% in GII tumors, and 20% in GI tumors. 16% of G0 tumors were cytologically positive. 33% of a total of 30 endoscopically detected recurrent GI-GIII tumors yielded negative results at bladder wash cytology, the findings were suspicious in 27%, while only 40% of all recurrences had a positive bladder wash cytology. Positive cytologic findings combined with normal endoscopic results were obtained in 24 patients. 15 of these (62%) developed recurrences after a mean interval of 15 months (3-60 months) during or after metaphylaxis. When suspicious findings were included, 20 of 30 carcinomas were detected, while 7 of 12 G0 tumors were overgraded. Bladder wash cytology has its merits for early detection of recurrences, since almost two thirds of the patients with positive cytologic findings and negative endoscopy developed a recurrent tumor at a later date. Whether or not positive cytology combined with negative endoscopic results should lead to therapeutic consequences remains to be discussed. PMID- 1752282 TI - Ultrasonography of urinary tract and micturition as an alternative to radiologic investigations in the spinal-cord-injured patient. AB - Over a period of 1.5 years (July 1989-Jan. 1991), a total of 504 patients, 442 of them suffering from spinal cord injuries with subsequent voiding disorders, were investigated by ultrasonography of the genitourinary tract. Ultrasonography of the upper urinary tract as well as the bladder and prostate provided and accurate image of the pathomorphological changes which go along with this kind of malfunction of the lower urinary tract in this group of patients. The application of rectal ultrasonography using a linear array rectal transducer was able to provide equal or even better images of the micturition process than micturition cystourethrography (MCU). An adequate and accurate real time image of the bladderneck, the prostatic urethra and the external rhabdosphincter could be obtained in all instances. Combined micturition cytourethrosonography (MCUS) with urodynamic evaluation has also been performed, which made the observation and judgement of the bladder outlet as well as the position of the catheter possible throughout the procedure without the interference of X-rays. PMID- 1752283 TI - Current concepts in cholesterol gallstone pathogenesis. PMID- 1752284 TI - Cyclosporin-A-induced lipid peroxidation in human liver microsomes and its influence on cytochrome P-450. AB - The present in vitro study using human liver tissue was performed to investigate the effect of cyclosporin A on lipid peroxidation and cytochrome P-450 concentration in isolated liver microsomes. Incubations were either carried out with cyclosporin A concentrations of 10, 30, 100 and 300 micrograms ml-1 for 1 h or for different time periods (15, 30, 60 and 90 min) with cyclosporin A 300 micrograms ml-1. Lipid peroxidation was monitored measuring the amount of malondialdehyde. In additional experiments the effect of reduced and oxidized glutathione (1 mM) on cyclosporin-A-induced lipid peroxidation in human liver microsomes was studied. Cyclosporin A caused a significant dose and time dependent increase of the lipid peroxidation product malondialdehyde. At the highest cyclosporin A concentration (300 micrograms ml-1) malondialdehyde production increased 5-fold in comparison to corresponding control values. Incubations for different time periods resulted in a 5-fold net increase of malondialdehyde formation after 90 min. In the presence of reduced glutathione, cyclosporin-A-induced lipid peroxidation was significantly inhibited. Furthermore, cyclosporin-A-induced microsomal lipid peroxidation was accompanied by a significant dose-dependent decline of the microsomal cytochrome P-450 content. At a cyclosporin A concentration of 300 micrograms ml-1, cytochrome P 450 content was decreased to 49% in comparison to control values. In the presence of reduced glutathione, cyclosporin A decreased the cytochrome P-450 concentration only to 79% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752285 TI - Copper metallothionein in patients with hepatic copper overload. AB - We studied the Cu-MT present in the hepatic cytosol obtained from 7 patients suffering from conditions associated with hepatic Cu overload (Wilson's disease, biliary atresia, familial cholestatic cirrhosis). Since chromatographic methods appropriate for the isolation of Zn- and Cd-MT were unsuitable for Cu-MT, we developed an indirect procedure for the estimation and resolution of the latter. This procedure involved the preparation of apo-MT and its reconstitution to holo MT with Zn or Cd. Three predominant isoforms of MT were present in all specimens. Our results indicate that at most 36 +/- 5% of the Cu present in the 10 kDa fraction of cytosol is bound to MT in the liver of patients with hepatic copper overload. PMID- 1752286 TI - Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients. AB - Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors. PMID- 1752287 TI - Alveolar macrophage chemotaxis in fire victims with smoke inhalation and burns injury. AB - In vitro migration of alveolar macrophages was studied in 24 fire victims and 19 controls; all subjects were cigarette smokers. Unstimulated (P = 0.01) and stimulated migration towards casein-(P = 0.01) and zymosan-activated serum (P = 0.002) of macrophages from smoke inhalation patients (SI) (n = 19) was increased when compared to control subjects (CS). Migration of alveolar macrophages from patients with burns without smoke inhalation (burns only, BO) was not increased. Patients with smoke inhalation and no burns (smoke only, SO) (n = 9) had increased migration when compared to controls but this was not statistically significant. Patients with smoke inhalation and burns (SB) (n = 10) had increased unstimulated migration (P = 0.01) and increased migration towards casein (P less than 0.005), ZAS (P less than 0.002) and F-met-leu-phe (P less than 0.05) when compared to controls (CS). Lavage fluid from the fire victims displayed chemotactic activity towards normal human neutrophils and its analysis for the components of the complement cascade proved positive (Clq, Clr, Factor B and C3). These data suggest that activation of alveolar macrophages may contribute to the development of pathophysiological changes in patients with smoke inhalation (SI) and particularly those with smoke inhalation and burns (SB). PMID- 1752288 TI - Platelet response to the aggregatory effect of platelet activating factor (PAF) ex vivo in patients with acute myocardial infarction. AB - Platelets from patients with acute myocardial infarction exhibit an increased sensitivity to the aggregatory effect of PAF, in vitro, the first 48 h after the onset of the symptoms. This sensitivity, expressed as PAF EC50 values, seems to be transient after the 2 day period. Also, a remarkable decreased sensitivity to the inhibitory effect of PGI2 against the aggregation induced by PAF appears to the platelets of those patients the first hours after the onset of the symptoms, and persists for at least 14 days. Treatment of patients by drugs with a known inhibitory effect on platelet aggregation in vivo and in vitro (aspirin, nifedipine, indomethacin), does not influence the increase in platelet sensitivity to PAF, but inhibits the secondary aggregation induced by the released aggregating factors from the PAF activated platelets. The increase in platelet sensitivity to PAF is not unique to the AMI since it is also observed in patients with acute bacterial pneumonia. However, we cannot support the theory that it is a general phenomenon of acute tissue injury since it is general phenomenon of acute tissue injury since it is not observed in patients with acute muscular injury. PMID- 1752289 TI - Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction. AB - A radioimmunoassay has been developed and used to measure serum neurone specific enolase (NSE) concentrations in 24 patients, following cerebral infarction. A significant correlation between cerebral infarct volume and maximum serum NSE concentration was observed (P = 0.047). Serum NSE was also assayed at times 24, 48, 72 and 96 h post ictus. At 72 h a significant correlation existed between serum NSE levels and infarct volume (P = 0.012), and levels appeared to be approaching statistical significance at 48 h (P = 0.067). No correlation existed at 24 and 96 h. In addition serum concentrations of NSE were compared to clinical outcome as determined by the Glasgow Outcome Score. Using the Mann-Whitney U test, there was no significant difference in maximum NSE level between patients graded 1-3 on the Glasgow Outcome Score and those graded 4 and 5. However, further studies are required on a larger population to more completely assess this. NSE may prove to be a useful marker of neuronal damage in the study of stroke, with particular application in the assessment of treatment. PMID- 1752290 TI - Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. AB - The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min 1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero insular axis in humans. PMID- 1752291 TI - The effect of angiotensin-I converting enzyme inhibition on insulin action in healthy volunteers. AB - Acute hyperinsulinaemia, achieving insulin levels within the physiological range, induces sodium retention. At the same time an activation of the renin-angiotensin system occurs, with a rise in plasma renin activity (PRA) and angiotensin-II level but no change in plasma aldosterone. After administration of higher, pharmacological doses of insulin an increase in systolic blood pressure and heart rate can also be observed, while further increases in PRA and angiotensin-II are noted. To determine whether angiotensin-II is involved in observed insulin actions, we studied the renal and cardiovascular effects of three dosages of insulin (50 (Ins I), 300 (Ins II) and 500 (Ins III) mU kg-1 h-1) in healthy subjects after one week of treatment with the angiotensin-I converting enzyme inhibitor enalapril (10 mg twice a day), using the euglycaemic clamp technique. Control data were obtained from two previously conducted experiments in the same subjects, one with infusion of insulin and one with the insulin solvent only. The effect of insulin on fractional sodium excretion, blood pressure and heart rate was unaffected by enalapril, which precludes any involvement of the renin angiotensin system with regard to these aspects of insulin action. Insulin sensitivity increased significantly during treatment with enalapril (with enalapril: Ins I: 11.3 +/- 3.0, Ins II: 20.0 +/- 3.4 and Ins III: 20.6 +/- 3.9 mg kg-1 min-1 glucose (mean +/- SD); without enalapril: Ins I: 8.7 +/- 2.3, Ins II: 13.7 +/- 3.0 and Ins III: 15.5 +/- 3.1 mg kg-1 min-1 glucose; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752292 TI - Adrenergic regulation of lipolysis in human fat cells during exercise. AB - The adrenergic regulation of lipolysis was studied, before and after 30 min of submaximal exercise, in isolated adipocytes removed from the abdominal and gluteal regions of healthy non-obese men and women. Noradrenaline-induced lipolysis was significantly enhanced in gluteal adipocytes from men but not in women after exercise. However, the pure beta-adrenergic responsiveness was equally increased in gluteal adipocytes of both sexes after exercise, as judged by the effect of isoprenaline. Furthermore, the alpha 2-adrenergic anti-lipolytic responsiveness was more apparent after exercise in females than in males thereby counter-balancing the increase in the beta-adrenergic effect in the gluteal region in the former. The increased beta-adrenergic responsiveness induced by exercise in gluteal adipocytes of males could be mimicked by agents acting at the levels of adenylate cyclase, coupling proteins, phosphodiesterase, and protein kinase and seems to be due to an adaptive enhancement at the hormone-sensitive lipase level. There was no change in the stoichiometric properties of beta adrenoceptors of gluteal adipocytes after exercise. Abdominal adipocytes of both sexes were four to five times more responsive to noradrenaline than gluteal ones. However, exercise induced no further enhancement of the catecholamine-stimulated lipolysis rate in fat cells from this site. Thus, the influence of exercise on catecholamine-stimulated lipolysis is regional and sex dependent. Men, but not women, have a greater ability to adapt lipolysis to increasing energy demands during exercise that are due to an acute increase in the effectiveness of the hormone-sensitive lipase complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752293 TI - Response of sympathetic nervous system activity to exercise in patients with congestive heart failure. AB - To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml-1); Normals: 547 +/- 37, I: 535 +/- 53, II: 867 +/- 87, III: 1033 +/- 157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients. PMID- 1752294 TI - Liquid crystal thermography as a screening test for deep vein thrombosis in patients with cerebral infarction. AB - Pulmonary embolism secondary to deep vein thrombosis is a frequent cause of death in stroke patients. In a multicentre study of deep vein thrombosis prophylaxis, 112 patients with cerebral infarction and leg paresis were given aspirin 300 mg three times a day (t.d.s.) alone or with dipyridamole 100 mg t.d.s. To screen for deep vein thrombosis liquid crystal thermography of the legs was performed daily for 15 days on all patients. Those patients with positive thermography underwent immediate X-ray venography of the appropriate limb as the definitive investigation for venous thrombosis. Twenty-two patients had positive thermograms, of whom 16 had confirmed deep vein thrombosis as demonstrated by X ray venography. Only 8 of the 22 had clinical signs of deep vein thrombosis and 2 of those had a negative venogram. Of the 14 patients with positive thermography but negative clinical signs 10 had positive venograms. Difference in the incidence of deep vein thrombosis in the two treatment groups was not demonstrated. It is concluded that occult deep venous thrombosis is common after ischaemic stroke and it can occur without clinical signs. Liquid crystal thermography is a simple, rapid and cheap screening test that will allow the detection of clinically unrecognized thrombosis. PMID- 1752295 TI - In vitro inhibition of Helicobacter pylori urease: biochemical and ultrastructural analysis. AB - Inhibition of H. pylori urease was studied by means of electron-microscopy and electrophoretic methods using different urease inhibitors, such as acetohydroxamic-acid (AHA), L-ascorbic acid (AsA), copper ions, a combination of L-ascorbic acid with copper ions and UV light. AHA in two different concentrations and AsA at a concentration of 0.1 mg ml-1 showed incomplete inhibition of H. pylori urease activity in our electrophoretic experiments. Only membrane-bound activity was inhibited with AHA but not the activity localized within the cytoplasma as demonstrated by electron-microscopy. AsA at a concentration of 0.5 mg ml-1 and the combination of copper ions (1 microgram ml 1) with AsA completely inhibited the urease activity as demonstrated by electron microscopy and electrophoretic experiments. Cu2+ ions in high concentrations (100 micrograms ml-1) and UV light exposure for more than 4 h induced a complete disintegration of H. pylori. Electrophoresis showed no active protein after UV light exposure of 2 h. Different urease inhibitors tested in this study showed dose-dependent inhibitory effects on H. pylori urease in vitro. PMID- 1752296 TI - Statistical methods applied in microbiology and epidemiology. PMID- 1752297 TI - Bacteriological quality of potable water sources supplying Morogoro municipality and its outskirts: a case study in Tanzania. AB - Bacteriological quality of potable water supplying Morogoro municipality and its outskirts (population 135,000 people) was assessed by the determination of the most probable number (MPN) of faecal coliforms, Escherichia coli, faecal streptococci and Clostridium perfringens for a period of 6 months. River water and chlorinated pipeborne water were found contaminated with microorganisms in the order of 3.8 x 10(1) to 4.95 x 10(3); 3.2 x 10(1) to 4.5 x 10(3); 10(1) to 6.4 x 10(1) and 1.2 x 10(1) to 2.5 x 10(2)/100 ml of water respectively. Injured coliforms in treated water averaged 87%. Pollution of river water by organic matter was much above acceptable standard. These findings indicate that there is a need for further treatment of water before consumption in order to avoid potential health hazards. PMID- 1752298 TI - An outbreak of waterborne cryptosporidiosis in Swindon and Oxfordshire. AB - An outbreak of cryptosporidiosis resulted in 516 cases in Wiltshire and Oxfordshire. The outbreak caused widespread interest and led to an official inquiry. The majority of cases were in children; 8% of cases were admitted to hospital and the median duration of illness was 3 weeks. The geographical distribution of cases matched the distribution of water supplies from three treatment works and cryptosporidium oocysts were found at these works and in the treated water. Attack rates in electoral wards supplied by the three treatment works were significantly higher than in other wards. The cause of the outbreak appeared to be the failure of normal treatment to remove oocysts. Measures at the treatment works reduced the number of oocysts detected in treated water, after which the outbreak came to an end. The conclusion of the investigations was that cryptosporidiosis is a risk of conventionally treated public water supplies. PMID- 1752299 TI - An outbreak of cryptosporidiosis associated with a swimming pool. AB - In August 1988 an increase was noted in the number of cases of cryptosporidiosis identified by the microbiology laboratory at Doncaster Royal Infirmary. By 31 October, 67 cases had been reported. Preliminary investigations implicated the use of one of two swimming pools at a local sports centre and oocysts were identified in the pool water. Inspection of the pool revealed significant plumbing defects which had allowed ingress of sewage from the main sewer into the circulating pool water. Epidemiological investigation confirmed an association between head immersion and illness. The pools were closed when oocysts were identified in the water and extensive cleaning and repair work was undertaken. The pool water was retested for cryptosporidial oocysts and found to be negative before the pool reopened. PMID- 1752300 TI - Cryptosporidiosis in the Isle of Thanet; an outbreak associated with local drinking water. AB - An outbreak of cryptosporidiosis occurred in the Isle of Thanet during December 1990 and January 1991. A total of 47 cases ranging in age from 2 months to 85 years were identified in residents from the Margate, Broadstairs and Ramsgate areas, with dates of onset of illness from 3 December to 14 January. A case control study demonstrated a strong statistical association between illness and the consumption of unboiled tap water from a particular source, with evidence of a dose-response relationship. Although no cryptosporidial oocysts were identified in samples of untreated or treated water taken during the investigation, the results were consistent with the view that the source of infection was treated river water which was used to supplement borehole water. PMID- 1752301 TI - The epidemiology of Salmonella in calves: the role of markets and vehicles. AB - Environmental contamination has been shown to be an important aspect of the epidemiology of salmonellosis in calves. Markets and transport vehicles are important links in the calf marketing chain and these were investigated to determine the level of salmonella contamination. Salmonellas were isolated from 7 of the 14 markets surveyed, with 31 of 838 samples (3.7%) being positive. Nine different salmonella serotypes, of which the commonest was Salmonella typhimurium, were isolated. Four different phage types of S. typhimurium were detected, the commonest being DT204C. Salmonellas were isolated from 22 of the 107 vehicles (20.6%) examined before washing and from 4 of the 62 vehicles (6.5%) examined after cleaning. Twelve different salmonella serotypes were isolated, of which the most frequent was S. typhimurium. The commonest of the six different S. typhimurium phage types was DT204C. These results indicate that improved cleaning and disinfection routines both for vehicles and markets are necessary to control salmonellosis in calves. PMID- 1752302 TI - Evaluating the sensitivity and predictive value of tests of recent infection: toxoplasmosis in pregnancy. AB - The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it. PMID- 1752303 TI - The population structure and transmission of Escherichia coli in an isolated human community; studies on an Antarctic base. AB - The population structure and transmission of Escherichia coli in a small group of individuals isolated for 26 weeks on an Antarctic base were studied by multilocus electrophoresis of eight enzymes and plasmid analysis. Two hundred and sixty-nine strains were isolated. They were grouped into 60 allozyme types (ETs). Half of these ETs were only isolated once; others were repeatedly isolated from single subjects. Eleven were found in more than one subject and the pattern of the occurrence of some of them was considered to provide evidence of their spread from subject to subject. PMID- 1752304 TI - Genotypic and phenotypic analysis of Streptococcus uberis isolated from bovine mammary secretions. AB - Genotypic and phenotypic analysis of 42 strains of Streptococcus uberis isolated from mammary secretions of 17 cows collected at different periods of the lactation cycle and from episodes of clinical mastitis were performed. Seventeen restriction endonuclease fingerprint (REF) patterns and 12 bacteriocin-like inhibitory substance (BLIS) fingerprints were observed. REF identified and differentiated closely related strains of S. uberis isolated from mammary secretions collected from the same cow at different periods of the lactation cycle and from episodes of clinical mastitis. BLIS fingerprinting of S. uberis complemented REF results. REF and BLIS fingerprinting provided evidence concerning persistence of infection in the same quarter or different quarters of the mammary gland over different periods of the lactation cycle, and occurrence of infection with similar and dissimilar strains of S. uberis. Biochemical profiles could not identify closely related strains nor did they complement REF results. Antibiotic resistance patterns alone were of little value in differentiating closely related strains, but were identical with isolates having same REF pattern. None of the S. uberis strains was found to carry plasmids. REF and BLIS fingerprinting can be utilized effectively to differentiate closely related and unrelated strains of S. uberis isolated from bovine mammary secretions. PMID- 1752305 TI - Phage typing of Staphylococcus saprophyticus. AB - This study included 502 staphylococcus strains; Staphylococcus saprophyticus (297 strains) S. cohnii (47), S. xylosus (10), S. epidermidis (67) and S. aureus (81). Mitomycin C induction was performed on 100 isolates of S. saprophyticus and all induced strains were reacted with each other. Twenty-six strains proved to be lysogenic. Phages were propagated and titrated. With 12 of the phages there were three frequent associations, named lytic groups A, B and C, which included 75% of all typable strains. Typability of the system was 45% and reproducibility was between 94.2% and 100%. Phages did not lyse S. aureus and S. epidermidis strains, but they lysed S. saprophyticus and only rare strains of other novobiocin resistant species. Effective S. saprophyticus typing serves ecological purposes and tracing the origin of urinary strains from the skin or mucous membranes. Phage typing in association with plasmid profiling previously described, are anticipated as complementary methods with strong discriminatory power for differentiating among S. saprophyticus strains. PMID- 1752306 TI - rDNA fingerprinting as a tool in epidemiological analysis of Salmonella typhi infections. AB - Characterization of 169 strains of Salmonella typhi of phage types C1, C4, D1 and D9 isolated in 1975-88 was carried out by rDNA gene restriction pattern analysis. Twenty-four isolates had been recovered during four large waterbone outbreaks in the last 20 years in Sicily; 145 strains, isolated from apparently sporadic cases of infection in Southern Italy in the same period of time, were also examined. Application of rRNA-DNA hybridization technique after digestion of chromosomal DNA with Cla I showed the identity of patterns of the epidemic strains of phage types C1 and D1, confirming attribution of the outbreaks to single bacterial clones. Patterns of the two available strains of lysotype D9 were slightly different, whilst the 12 epidemic strains of phage type C4 could be assigned to two distinct patterns scarcely related to each other and, consequently, to two different clones. A considerable heterogeneity was detected among all apparently sporadic isolates of the four phage types under study. This fingerprinting method appears a reliable tool to complement phage typing in characterizing isolates of S. typhi. In particular, epidemiological features of spread of this salmonella serovar in areas, where simultaneous circulation of indigenous and imported strains occurs, can be elucidated. PMID- 1752307 TI - Changing trends of gonococcal infection in homosexual men in Edinburgh. AB - In an attempt to explain the recent resurgence of homosexually-acquired gonorrhoea in the Lothian region of Scotland the number of infections and pattern of infection (urethral, rectal and pharyngeal) of all gonococcal isolates from homosexual men attending the Department of Genitourinary Medicine at Edinburgh Royal Infirmary between 1985 and 1990 were analysed. Serovar typing data were available from infections acquired between January 1986 and December 1990. A correlation between one serovar, Bacejk/Brpyust, and the overall pattern of gonorrhoea was observed. The number of infections caused by minor serovars also correlated with rates of gonococcal infection. The number of minor serovars isolated, which may represent strains from other geographical locations, is related to the total incidence of gonorrhoea. It is possible that the incidence of Bacejk/Brpyust may be determined by the size of the infected pool of gonorrhoea. The most likely explanation for the recent increase in gonorrhoea is a change in sexual behaviour and/or an influx of strains from other geographical areas. PMID- 1752308 TI - Control of endemic nosocomial legionnaires' disease by using sterile potable water for high risk patients. AB - In a setting where potable water is contaminated with Legionella pneumophila serogroup 1, we performed two case control studies. The first case control study consisted of 17 cases of nosocomial Legionnaires' disease (LD) and 33 control (the patients who were admitted to the ward where the case was admitted immediately before and after the case) subjects. Cases had a higher mortality rate 65% vs 12% (P less than 0.004); were more likely to have received assisted ventilation (P less than 0.00001); to have nasogastric tubes (P less than 0.0004) and to be receiving corticosteroids or other immunosuppressive therapy (P less than 0.0001). Based on the results of this study, sterile water was used to flush nasogastric tubes and to dilute nasogastric feeds. Only 3 cases of nosocomial LD occurred during the next year compared with 12 the previous year (P less than 0.0001). Nine cases subsequently occurred and formed the basis for the second case-control study. Eighteen control subjects were those patients admitted to the same unit where the case developed LD, immediately before and after the case. The mortality rate for the cases was 89% vs 6% for controls (P less than 0.00003). The only other significant difference was that cases were more likely to be receiving corticosteroids or other immunosuppressive therapy 89% vs 39% (less than 0.01). We hypothesized that microaspiration of contaminated potable water by immunocompromised patients was a risk factor for nosocomial Legionnaires' disease. From 17 March 1989 onwards such patients were given only sterile potable water. Only two cases of nosocomial LD occurred from June 1989 to September 1990 and both occurred on units where the sterile water policy was not in effect. We conclude that aspiration of contaminated potable water is a possible route for acquisition of nosocomial LD in our hospital and that provision of sterile potable water to high risk patients (those who are receiving corticosteroids or other immunosuppressive drugs; organ transplant recipients or hospitalized in an intensive care unit) should be mandatory. PMID- 1752309 TI - Differentiation of strains of Helicobacter pylori by numerical analysis of 1-D SDS-PAGE protein patterns: evidence for post-treatment recrudescence. AB - Twenty-three pre- and post-treatment isolates of Helicobacter pylori from the antral mucosa of eight patients with dyspepsia and gastritis were compared using 1-D SDS PAGE of proteins. The protein patterns were highly reproducible and were used as the basis for two numerical analyses. The first, based on the total protein patterns, showed that a number of the strains did not cluster with their respective patient set. This was thought to be due to differences in both mobility and intensity of proteins in the major band region. The second analysis, based on partial patterns, excluding the major band region (51-68 kDa), divided the clinical isolates into clearly defined groups corresponding to the patient sets. Although there was a degree of heterogeneity with respect to protein pattern between the pre- and post-treatment isolates of some patients, there was nonetheless clear evidence that each patient was harbouring strains of only a single type. These results suggested that patients were not being reinfected with a different strain but that there was recrudescence of the pre-treatment strain. Protein 'fingerprints' provided a precise and reproducible means of strain differentiation, and revealed that in each patient the same strain persisted after drug therapy even though there was marked patient-to-patient strain variation. PMID- 1752310 TI - Study of colonization resistance for Enterobacteriaceae in man by experimental contamination and biotyping as well as the possible role of antibodies in the clearance of these bacteria from the intestines. AB - The colonization resistance (CR) of the digestive tract was determined in 10 healthy volunteers by oral contamination with a neomycin resistant Escherichia coli (NR-E. coli) strain and measurement of the faecal concentration of this strain during 14 days after the contamination. This 'gold standard' was compared with another parameter of CR; the determination of the mean number of different biotypes of Enterobacteriaceae isolated from four faecal samples per volunteer. Both measures are significantly correlated (P less than 0.01). The NR-E. coli strain could be cultured from faecal samples of 4/10 volunteers as long as 300 days after contamination. Serum antibody titres against endogenous E. coli strains and the NR-E. coli strain used for experimental oral contamination were measured by an indirect immunofluorescence (IIF) assay. The assay was read by a video camera connected to an image processing system. The 95% confidence limits of antibody titres (log2) against endogenous E. coli strains ranged between less than 3 and 7.1 for IgA, between less than 3 and 8.7 for IgG and between less than 3 and 7.4 for IgM. Antibody titres against the NR-E. coli4 strain were within this (normal) range. The serum antibody titres against the NR-E. coli strain increased slowly after oral contamination, especially IgG and IgM. Little increase in IgA titres could be observed. An increase of serum antibody titres did not correlate with the elimination of the oral contaminant from the intestines. Therefore, we conclude that the CR is not IgG nor IgM antibody mediated. PMID- 1752311 TI - Relapse versus reinfection with Clostridium difficile. AB - Relapse of Clostridium difficile-associated diarrhoea occurs in 15-20% of patients; however, whether relapse is due to an endogenous source of the organism or reinfection from the environment remains unclear. Restriction enzyme analysis (REA) of chromosomal DNA was used to type multiple isolates from ten patients who had experienced apparent relapses. More than half the relapses were due to infection with a new strain of C. difficile. The remaining patients were infected with the same strain, but whether this strain was acquired from the environment or from endogenous sources could not be determined. Relapses with a different strain of C. difficile could occur if an individual harboured more than one strain in their gastrointestinal tract. To investigate this possibility ten other patients were assessed for carriage of multiple strains. Ten colonies from a primary culture plate from each patient were typed by REA and tested for their ability to produce cytotoxin. All isolates from the same patient were identical by both methods, indicating that multiple carriage of strains may be a rare event. PMID- 1752312 TI - Characterization of a protective protein antigen of Erysipelothrix rhusiopathiae. AB - Although vaccination is widely practiced against infection by Erysipelothrix rhusiopathiae in pigs and turkeys, the protective antigen(s) involved have not been fully characterized or purified to homogeneity. Antigens of E. rhusiopathiae strain T28, serotype 2b, and of FRANKFURT XI, serotype N, in culture supernatant and in extracts made with hot acid, 10 mM NaOH, ultrasound or EDTA were compared by SDS-PAGE and immunoblotting and in a mouse protection test. EDTA and 10 mM NaOH yielded highly protective extracts; culture supernatant was less protective and ultrasonic or hot acid extracts stimulated little or no protection in mice. Protective antisera from swine, horses and mice recognized prominent bands of molecular mass (m.m.) of 66-64 and 40-39 kDa in EDTA and 10 mM NaOH extracts. Mice immunized with preparations of the 66-64 kDa band purified by preparative electrophoresis were protected. Both antigens were trypsin sensitive, contained no detectable polysaccharide, and showed a marked tendency to aggregate in the absence of SDS. PMID- 1752313 TI - Gastrointestinal carriage of Clostridium difficile in cats and dogs attending veterinary clinics. AB - Cats and dogs being treated at two veterinary clinics were investigated for gastrointestinal carriage of Clostridium difficile using selective solid and enrichment media. Thirty-two (39.5%) of 81 stool samples yielded C. difficile. There were significant differences in isolation rates between clinics, 61.0% of animals being positive at one clinic compared to 17.5% at the other (Chi-square, P less than 0.005). Of 29 animals receiving antibiotics, 15 (52.0%) harboured C. difficile while 11 (23.9%) of 46 animals not receiving antibiotics were positive (Chi-square, P less than 0.01). There was no difference in carriage rate between cats (38.1%) and dogs (40.0%). The environment at both veterinary clinics was surveyed for the presence of C. difficile. Fifteen of 20 sites at one clinic were positive compared to 6 of 14 sites at the other clinic. Both cytotoxigenic and noncytotoxigenic isolates of C. difficile were recovered from animals and environmental sites. These findings suggest that household pets may be a potentially significant reservoir of infection with C. difficile. PMID- 1752314 TI - Evaluation of enzyme immunoassay (EIA) as a screening method for hepatitis B markers in an open population. AB - Commercially available kits for detection of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) by enzyme immunoassay (EIA) were evaluated in American Samoa during a public health programme to eliminate the transmission of hepatitis B. The first 19,184 serum specimens obtained, representing 68% of the total cooperating population, were initially tested for anti-HBs, and those without detectable antibody were tested for HBsAg. All the antigen-positive serum samples, and a selection of the antigen- and antibody negative specimens were tested by radioimmunoassay (RIA) for detection of both markers. Compared with the standard tests, the EIA kits for anti-HBs and HBsAg performed well; sensitivity and specificity were 90.3 and 96.0%, respectively, for antibody, and 97.8 and 97.9% respectively for antigen. Substantial disagreement between the EIA and RIA tests for HBsAg was found only for specimens considered weakly reactive by EIA. Few differences were found between three EIA method options for follow-up HBsAg testing of weakly reactive serum specimens; each option contributed about equally to improved test specificity for these 'borderline' specimens. Based on their demonstrated equivalence to the standard RIA tests, we conclude that the EIA kits for anti-HBs and HBsAg detection are suitable for use in hepatitis B control programmes in open populations. PMID- 1752315 TI - Reticulo-fibroblastoid stromal cell progenitors (CFU-RF) in murine bone marrow. AB - The hemopoietic inductive microenvironment (HIM) of the bone marrow is responsible for secretion of growth factors that regulate hemopoiesis. It is composed of an extracellular matrix and a complex variety of cell types with a range of functions related to blood cell development. In order to understand how such a complex system operates, it will first be necessary to determine the role(s) of the integral parts. Several of the stromal cell types have been identified morphologically in various culture systems, and some of their functions have been elucidated. We have identified a new stromal cell type in mouse bone marrow that appears similar if not identical to its human counterpart. When bone marrow cells are placed in methylcellulose/plasma clot culture with phytohemagglutinin-stimulated human leukocyte-conditioned medium in the presence of bovine calf serum (BCS), mercaptoethanol, and hydrocortisone, extensive branching colonies develop within 14 days. These "reticulo-fibroblastoid" (RF) colonies arise from a putative reticulo-fibroblastoid colony-forming unit (CFU RF) stem cell, and many become adipocytic by day 14; the addition of fresh medium, methylcellulose, and BCS on day 7 inhibits this change. The batch of human citrated plasma used in the culture system and the type and source of stimulating factor all influence the number of RF colonies that develop as well as the percent of colonies that become adipocytic. Whether this adipogenesis represents functional maturity or terminal differentiation is not yet known. Information gained on the role of these RF cells in normal and impaired hemopoiesis should contribute to the elucidation of the complicated interactive role of the microenvironment in the support and modulation of hemopoiesis. PMID- 1752316 TI - Megakaryocyte maturation in long-term marrow culture. AB - Evidence has been sought for megakaryocyte maturation in long-term cultures of mouse bone marrow. Cultures up to 14 weeks of age were examined for the presence of megakaryocytes with processes, that is, resembling the morphological appearance seen in vivo prior to platelet liberation. Such cells were found floating just above the adherent stromal layer using low magnification phase contrast microscopy. It was rare to observe as many as 20 of these cells per 25 cm2 flask. At higher magnification, processes were seen to be attenuated with constrictions at intervals along their length. Time-lapse photography was used to follow the development and behavior of the processes. Direct evidence of rupture was very rare; generally the megakaryocytes retracted their processes within 48 h. Careful searching of cultures occasionally revealed the presence of several process fragments, and sometimes individual platelets were found. Ultrastructurally, the processes were seen to contain organelles that are usually associated with platelets. The observations applied to both Dexter and Whitlock Witte cultures. It is concluded that maturation of megakaryocytes occurs in long term marrow culture to the point where platelet release appears imminent. Final rupture is rare and may require shearing forces, which in vivo would be provided by blood flow. PMID- 1752317 TI - Responsiveness of highly enriched CFU-GM subpopulations from bone marrow, peripheral blood, and cord blood to hemopoietic growth inhibitors. AB - Human early and late granulocyte-monocyte progenitors (granulocyte-macrophage colony-forming units, CFU-GM), depleted of accessory cells, were physically separated using an antimyeloid monoclonal antibody (DS1.1). They were separately cultured at optimal growth conditions and tested for responsiveness to prostaglandin E2 (PGE2), recombinant tumor necrosis factor alpha (TNF alpha), and transforming growth factor beta-1 (TGF beta 1). Late (DS1.1+) CFU-GM displayed the highest sensitivity to PGE2 and TNF alpha, the first significant inhibition being evident at 10(-9)M PGE2 and 1 U/ml TNF alpha. Conversely, their growth was stimulated (211%-217%) by 0.25-2.5 ng/ml TGF beta 1. Early (DS1.1-) marrow CFU-GM evidenced a lower sensitivity to PGE2 and TNF alpha. Their growth, however, was inhibited by 0.25-2.5 ng/ml TGF beta 1. Early CFU-GM constitute the totality of peripheral blood myeloid progenitors. Cord blood CFU-GM were also demonstrated here to be entirely DS1.1-. Both adult and cord blood CFU-GM displayed the highest resistance to PGE2 and TNF alpha. By contrast, they showed the maximum sensitivity to growth inhibition by TGF beta 1, active at 0.025-0.25 ng/ml. For the first time, therefore, highly purified subsets of human CFU-GM were separated that displayed a different responsiveness to well-defined growth-regulatory molecules. Our results indicate that TGF beta 1 has a dual activity; it is inhibitory on early and stimulatory on late CFU-GM, whereas PGE2 and TNF alpha preferentially inhibit late CFU-GM growth. PMID- 1752318 TI - Effects of erythroid differentiation factor (EDF) on proliferation and differentiation of human hematopoietic progenitors. AB - The effects of erythroid differentiation factor (EDF) on normal human hematopoietic progenitor cells were examined by bone marrow colony assay. Addition of EDF to the erythroid colony assay system enhanced erythroid burst forming unit (BFU-E)-derived colony formation, and this effect disappeared on removal of adherent cells. Conditioned medium of EDF-treated monocytes also enhanced BFU-E colony formation, whereas conditioned medium of EDF-treated T cells did not. In contrast, EDF inhibited erythroid colony-forming unit (CFU-E) colony formation dose-dependently, although it had no effect on colony formation by myeloid cells. These data show that EDF has a specific effect on human hematopoietic progenitors of the erythroid lineage. The results also indicate that EDF enhanced BFU-E colony formation by stimulating adherent cells to produce factors with burst-promoting activity (BPA), but suppressed CFU-E colony formation by promoting differentiation of these cells. PMID- 1752319 TI - The thermal response and development of thermotolerance of the bone marrow stromal progenitor CFU-F. AB - The effect of hyperthermia on the murine bone marrow stromal progenitor (fibroblast colony-forming unit, CFU-F) was evaluated and its ability to develop thermotolerance demonstrated. CFU-F were obtained from nucleated marrow of Balb/c mice and heated in vitro in alpha minimum essential medium plus 15% fetal bovine serum. Thermotolerance development was tested two ways. 1) The development of thermotolerance during prolonged hyperthermia was observed with a "step-up" heating protocol (i.e., cells were incubated at 41 degrees C and at regular intervals challenged with 15 min at 44 degrees C). 2) The development of thermotolerance at 37 degrees C after a short exposure to a high temperature (greater than or equal to 43 degrees C) was observed with a split treatment protocol that consisted of two 15-min treatments of 44 degrees C separated with time at 37 degrees C. The inverse of the slopes of the hyperthermia dose-response relationships (Do +/- SE) for CFU-F were 118 +/- 14, 53 +/- 7, 23 +/- 0.6, 11 +/- 0.3, 7 +/- 0.3, and 5 +/- 0.5 min for exposures of 41.5 degrees, 42 degrees, 42.5 degrees, 43 degrees, 43.5 degrees, and 44 degrees C, respectively. The plot of the slopes of the heat "dose-response" relationships versus the inverse of the absolute temperature (Arrhenius plot) yields a change in slope at approximately 43 degrees C, and the inactivation enthalpies (slopes above and below the inflection point at 43 degrees C) were 606 +/- 100 kJ/mol (145 +/- 24 kcal/mol) and 1372 +/- 29 kJ/mol (328 +/- 7 kcal/mol) above and below 43 degrees C, respectively. The maximum thermotolerance ratio (TTR, surviving fraction after maximum thermotolerance development to surviving fraction of normotolerant CFU-F) at 37 degrees C after an acute thermal exposure to 15 min at 44 degrees C occurred after 12 h, with a half time of 60 min and a TTR of 41. The maximum TTR during prolonged hyperthermia at 41 degrees C was 2.4 by approximately 50 min. These results show that CFU-F are as sensitive as committed hematopoietic precursors (e.g., granulocyte-macrophage colony-forming units, CFU-GM) to hyperthermia over a wide range of thermal exposures and are capable of thermotolerance development during prolonged hyperthermic exposures and at 37 degrees C after short exposures. We conclude that at least one of the stromal elements of normal marrow may be compromised during whole-body or regional clinical hyperthermia protocols. PMID- 1752320 TI - Toxic effects on the hematopoietic microenvironment. PMID- 1752321 TI - The International Society for Experimental Hematology meeting. PMID- 1752322 TI - Manual of food quality control. 6. Food for export. PMID- 1752323 TI - [The current principles of managing delivery]. PMID- 1752324 TI - [Abscess of the greater vestibular gland of the vagina]. PMID- 1752325 TI - [The follow-up of the psychomotor development of infants in the 1st year of life in a pediatric polyclinic]. PMID- 1752326 TI - [The characteristics of hematopoiesis and the composition of the blood in children]. PMID- 1752327 TI - [Osteogenic sarcoma and Ewing's sarcoma in children]. PMID- 1752328 TI - [First aid in anaphylactic shock]. PMID- 1752329 TI - [The problems of the sexual adaptation of young newlyweds]. PMID- 1752330 TI - [Viral hepatitis and pregnancy]. PMID- 1752331 TI - [Faucial diphtheria]. PMID- 1752332 TI - [Myocardial infarct and cardiogenic shock]. PMID- 1752333 TI - [Chronic endometritis]. PMID- 1752334 TI - [New organizational forms of delivering medical care abroad]. PMID- 1752335 TI - [Ecology and health]. PMID- 1752336 TI - [A study of anti-pituitary-antibodies in patients with hypopituitarism and their hereditary background]. AB - Recently several types of anti-pituitary-antibodies (APA) have been found in patients with pituitary disorders including hypopituitarism and diabetes insipidus, and in postpartum women. However, the pathophysiological role(s) of APA still remains unknown. In order to elucidate the clinical significance of APA, longitudinal follow-up and family study of APA in patients with hypopituitarism were performed. APA in serum was examined in a total of 11 patients with various types of hypopituitarism (7 of isolated ACTH deficiency, 1 of partial hypopituitarism, 3 of Sheehan's syndrome, 6 males and 5 females). Chronic thyroiditis was associated in 3 out of 7 patients with isolated ACTH deficiency, and empty sella was found in each one patient with isolated ACTH deficiency and partial hypopituitarism, and in 3 patients with Sheehan's syndrome. APA was examined on 2 or 3 occasions at more than a 6 month interval (longitudinal study). In 5 patients, their 16 family members were examined for the presence of APA, and pituitary functions were evaluated in 3 out of 7 family members with positive APA (family study). For pituitary function tests, arginine infusion test, TRH, LH-RH or CRH test and insulin tolerance test were performed. APA reacting to rat pituitary cytoplasmic antigens (pituitary cell antibodies: PCA) and APA reacting to rat GH3 cells and/or mouse AtT20 cells surface antigens (pituitary cell surface antibodies: PCSA) were assayed with indirect immunofluorescence method. At the initial examination, 6 out of 11 patients (55%) showed positive APA. The patients were divided into 3 subgroups according to the longitudinal study: the group with disappearance of initially positive APA (3 patients), the group with altered titers or types of initially positive APA (3 patients), and the group with sustained initially negative APA (4 patients). No effects of replacement therapy on the alterations of APA were observed. In 16 family members of 5 patients (each 1 with partial hypopituitarism and isolated ACTH deficiency syndrome, and 3 with Sheehan's syndrome), APA in their sera were investigated. Seven out of 16 members (44%) showed positive APA. Among 6 first degree relatives of 16 family members, both or either one of APA and PCSA were positive in 4 (67%). Out of 10 of their second- or third-degree relatives, 3 (30%) were positive for PCA or PCSA. All of 3 relatives with positive APA studied showed mild pituitary hypofunction without any clinical manifestations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1752337 TI - [Effect of growth hormone on immune function in normal and hypophysectomised rats]. AB - The effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age. In hypophysectomised rats, the counts of peripheral white blood cells (5,513 +/- 813/microliters), lymphocytes (4,838 +/- 737/microliters), Th/i cells (2,237 +/- 329/microliters), and B cells (1,400 +/- 509/microliters), Th/i/Ts/c ratio (1.78 +/- 0.27), splenic T cell subsets (pan T: 51.0 +/- 4.3%, Th/i: 31.6 +/- 3.0%, Ts/c: 23.9 +/- 2.7%), and serum IgG level (2,148 +/- 470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8 +/- 4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1 +/- 15.7, PHA: 51.6 +/- 12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850 +/- 840/microliters), lymphocytes (6,211 +/- 731/microliters), Th/i cells (2,909 +/- 304/microliters), and B cells (1,947 +/- 402/microliters), Th/i/Ts/c ratio (2.04 +/- 0.34), serum IgG level (3,414 +/- 1,326mg/l), and natural killer activity (25.7 +/- 4.7%). However, splenic lymphocyte subsets and mitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982 +/- 1,496mg/l) but did not affect other immunological parameters. These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function. PMID- 1752338 TI - [Studies on the iodide metabolism and the expression of thyroglobulin and thyroid peroxidase mRNA in the thyroid of BB/W rats]. AB - BioBreeding/Worcester (BB/W) rats develop insulin dependent diabetes mellitus (IDDM) and lymphocytic thyroiditis (LT) spontaneously. Our previous studies have shown that BB/W (Saitama-Tokyo colony) rats develop LT at about 10 weeks of age. Their serum TSH values increase as LT extends, although their serum thyroid hormone levels remain normal. This indicates that BB/W rats suffer from subclinical hypothyroidism. To investigate whether BB/W rats have a defect in iodide metabolism, the thyroidal radioactive iodine uptake (RAIU) in BB/W rats was examined. Thyroidal RAIU at 3hr in both 8 and 16 week-old BB/W rats was significantly higher than that in age-matched normal Wistar rats. On the other hand, BB/W rats had significantly lower 48hr thyroidal RAIU than normal Wistar rats. This suggests that BB/W rats appear to have some defects in iodide metabolism, especially in iodide organification even before the development of LT. The expression of thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA in BB/W and Wistar rats was then examined using the Northern blot analysis. The expression of both TPO and Tg mRNA was greatly decreased in BB/W rats compared with that in Wistar rats despite the high serum TSH levels in BB/W rats. This indicates that BB/W rats may have pretranslational defects in TPO and Tg synthesis, resulting in the impaired thyroid hormone synthesis. In the present study, it has been demonstrated that BB/W rats appear to have a defect(s) in iodide metabolism possibly due to some abnormalities in TPO and Tg synthesis. PMID- 1752339 TI - [Enzymatic iodination of thyroglobulins obtained from patients with thyroid disease]. AB - Iodination of the isolated thyroglobulin (Tg) by peroxidase was compared with various Tg preparations obtained from patients with thyroid diseases. For the purpose, the iodination process was observed in the incubation medium containing Tg, iodide, H2O2-generating system, and thyroid peroxidase (TPO) or lactoperoxidase (LPO). During the incubation, iodination of Tg preparations increased gradually and reached a plateau after 90 min., and 5 min. incubation with 3mIU or 14mIU of TPO, respectively. The degree of iodination level at the plateau region was different in each Tg preparation, depending on the iodine content of the original starting (native) preparation before incubation. The iodination level of cancer Tg with a very low iodine content (less than 0.1%) was low compared with the normal Tg level (obtained from normal thyroid tissue which contained about 0.4% iodine). The above findings suggest the possible existence of some structural differences of Tg in terms of the susceptibility to the iodination between the preparations of normal and diseased Tgs. As far as the immunological aspect concerned, there was no significant difference in the affinity (avidity) of Tg with polyclonal anti-Tg antibody between the native Tg and the enzymatically iodinated one. These results suggest that the changes of iodine and thyroid hormone contents of Tg by in vitro iodination, has no significant effect on the immunological property of Tg molecule. PMID- 1752340 TI - [Study of the predictive factors of postoperative blood pressure in cases with primary aldosteronism]. AB - Some patients develop hypertension after adrenalectomy for primary aldosteronism. We treated 60 cases with primary aldosteronism, and the percentages of cases manifesting hypertensive blood pressures after operation were as follows: 40.0% at the first month, 24.2% at the second year, 30.4% at the 5th year after operation. What are the most important clinical factors relating to postoperative blood pressure? Knowledge of those factors would help in predicting the postoperative blood pressure in cases with primary aldosteronism. The relationships between the postoperative blood pressure and several clinical factors were evaluated for a certain postoperative period using multiple regression analyses. The results were as follows: 1. The duration of preoperative hypertension is the major determinant at the second month after operation. 2. The histological findings for the kidney are the major determinant at the 6th month and the first year after operation. 3. At the second year postoperation, the histological findings for the kidney and the familial history of hypertension are the major determinant respectively. 4. The familial history of hypertension is the most determinant at the 5th year after operation. It is concluded that the preoperative duration of hypertension and the histological findings for the kidney are helpful in predicting blood pressure during the first 2 years after operation, while the familial history of hypertension influences the postoperative blood pressure thereafter. PMID- 1752342 TI - [The 64th Fall Meeting of the Japan Endocrine Society, Maebashi, November 14-15, 1991 and 18th Meeting of the Neuroendocrinology Subsection of the Society, Tokyo, November 17, 1991. Abstracts]. PMID- 1752341 TI - [A case of dwarfism with severely reduced activity of growth hormone-binding protein]. AB - We presented a 16-year-old boy with severe growth retardation and markedly decreased levels of growth hormone-binding protein (GHBP) in plasma, which was shown to correspond to the extracellular composition of hepatic GH receptor and suggested to reflect tissue concentration of the receptor. His height was 92.5 cm (-13.5 SD), the weight 9.6kg (-5.8 SD) and Tanner stage was I. His bone age was 3.5 years old at 16 years of age. Karyotype was 46,XY and thyroid function was normal. SM-C levels, determined by Nichols RIA using unextracted plasma, were within the low normal range, 0.67/0.68U/ml. In contrast, using a method of acid ethanol extraction, IGF-I and IGF-II levels were definitely low, 29ng/ml (normal 88-240) and 165ng/ml (374-804) respectively. GH responses in various provocation tests, including insulin, arginine and GRF, were within normal. Basal GH levels were 20 +/- 12ng/ml and urinary GH excretion rates 217 +/- 85pg/mg. Cr, which were elevated compared to age-matched control. Molecular size of his circulating GH was similar to control subjects. The biological activities of GH, evaluated by radioreceptor assay and Nb2 cell bioassay, were proportional to the immunoactivities of GH. SM bioactivities, which were determined by the stimulatory effects on DNA synthesis of rabbit costal chondrocytes and human fibroblasts, were apparently reduced. Electrophoretic patterns of IGF-binding protein was similar to those of GH deficient cases. Daily administration of hGH (4U/day) for 5 days resulted in a poor response of SM-C production (before 0.68, after 0.77U/ml). GHBP activities were definitely low by gel-filtration, immunoprecipitation and charcoal methods, as seen in Laron dwarfism which is defined as a syndrome of congenital GH receptor defects. These results indicate that the tissue content of GH receptor in this case was quantitatively reduced and as a result, he showed a resistance to endogenous and exogenous GH. It remains to be elucidated whether the GH receptor defect in our case is derived from a genetic origin or an acquired condition. PMID- 1752343 TI - The insulin-like properties of vanadium: a curiosity or a perspective for the treatment of diabetes? AB - Vanadium is a trace metal that has raised increasing interest in diabetology since the discovery of its insulin-like properties in vitro and in vivo. This brief article is a review of the most recent data concerning the cellular mechanisms by which vanadium salts stimulate glucose metabolism. The beneficial effects of vanadium on glucose homeostasis of animal models of insulinopenic or insulin-resistant diabetes are discussed. The perspectives that the use of vanadium opens for the treatment of diabetes are also considered, in the light of the potential toxicity of the element. PMID- 1752344 TI - Restoration of sensitivity to sulfonylurea after strict glycaemic control with insulin in non-obese type 2 diabetic subjects. AB - Ten non-obese type 2 diabetic patients with secondary failure to sulfonylureas received an intensive insulin therapy (four doses schedule) for 90 days. The glycaemic control was poor at entry (HbA1c = 11.7 +/- 1.2%) and ameliorated significantly after insulin (HbA1c = 7.1 +/- 0.7%, p less than 0.01). The reintroduction of the sulfonylurea after insulin withdrawal resulted in a persistent satisfactory long-term control (300 days) in all, but two diabetics responded no more after about 3 and 4 months of clinical remission (good control on sulfonylurea). Both basal and stimulated (iv glucagon and mixed meal) beta cell secretory activity increased significantly at 3 months and declined thereafter without falling below baseline values. Three months of strict metabolic control seem to restore the sensitivity to sulfonylurea by enhancing beta-cell secretory activity in non-obese type 2 diabetic patients. PMID- 1752345 TI - [Psychological aspects of remission induced by intensive insulin therapy in type I diabetes. A retrospective study of 44 patients]. AB - The psychological consequences of induced remission of type 1 diabetes, have not yet been investigated thoroughly. We studied the psychological status of 44 patients (16 women, 28 men), age 21 years +/- 8 months (mean +/- SD), whose remission lasted 12 +/- 9 months. Patients' psychological reactions were analyzed retrospectively, using a 20 items standardized questionnaire, investigating 3 successive periods: 1) initial intensive insulin therapy; 2) remission; 3) permanent insulin therapy. 8% of the subjects only considered the remission phase useless, whereas 49% expressed a positive appraisal. Hope was predominant feeling, 25% of the patients believing in a completed recovery of diabetes. Perceived therapeutic constraints were, in decreasing order: regimen, way of life's regularity, self monitoring of blood glucose. When starting permanent insulin therapy, opposite answers were given: 49% negative feelings, 33% positive feelings and 18% ambivalent feelings. During this period, insulin injections represented the major therapeutic constraint, followed by self monitoring of blood glucose. To summarize, induced remission does not appear to be psychologically harmful and is considered useful by a large majority of patients. Effective psychological support has to be offered to help those patients to cope with their irrational hopes of healing and to dampen their deception at the end of the remission period. PMID- 1752346 TI - Variation of insulin absorption during subcutaneous and peritoneal infusion in insulin-dependent diabetic patients with unsatisfactory long-term glycaemic response to continuous subcutaneous insulin infusion. AB - The aim of present study was to analyse the reproducibility of plasma-free insulin profiles of subcutaneously (CSII) and intraperitoneally (CIPII) administered insulin in 6 C-peptide-negative, type 1, diabetic patients. The patients were selected for CIPII because of unsatisfactory, long-term, metabolic response to CSII. Plasma-free insulin was measured repeatedly, twice during subcutaneous infusion and twice during intraperitoneal infusion, for 4 hours, following a standard breakfast. In the CSII experiment, insulin was given as a meal-dose of 0.1 U per kg body weight, and in the CIPII experiment the meal-dose was 0.05 U per kg body weight. The dose-induced peak occurred earlier after the CIPII than with the CSII (60.0 +/- 8.0 vs 133.6 +/- 16.3 min). In conclusion, the intra-patient coefficient of variation (C.V.) of plasma-free-insulin profiles at 0-60 min and 0.240 min, as well as the peak time, were markedly lower for CIPII insulin than for CSII, indicating a more reproducible way of insulin administration with CIPII in this selected group of patients. PMID- 1752347 TI - Age, sex and ICA influence on beta-cell secretion during the first year after the diagnosis of type 1 diabetes mellitus. AB - We studied the independent influence of sex, age and islet-cell antibodies (ICA) on residual beta-cell secretion and metabolic control during the first year after the diagnosis of type 1 diabetes mellitus in 40 consecutive newly diagnosed patients. Glucagon-stimulated C-peptide secretion was measured after 5-10 days and 3, 6 and 12 months of diagnosis. ICA (JDF units) and complement-fixing ICA (CF-ICA) were determined at diagnosis and after 12 months. The influence of sex, age and ICA was analyzed in a multivariate analysis of variance of 3 factors (age, sex and ICA) for repeated measures over time. ICA and CF-ICA were positive in 75.0% and 35.0% of patients at diagnosis and in 48.7% and 20.5% of patients one year later. Persistence of ICA positivity was higher in females (p. less than 0.001) and in CF-ICA+ patients (p less than 0.01), but did not involve a different evolution of C-peptide secretion. Males had a lower C-peptide secretion than females (p = 0.023) during the first year after the diagnosis of type 1 diabetes, independently of the age and ICA status of the patients. Adult patients (greater than or equal to 18 years-old) had lower HbA1 values than younger patients (p = 0.006) and ICA+ patients with a moderate or high value (greater than 10 JDF units) had a lower C-peptide secretion over time (p = 0.031 at 6 months, p = 0.067 at 12 months) and higher HbA1 values (p = 0.056) than younger patients. HbA1 was significantly explained by ICA and C-peptide values in a stepwise multiple regression analysis (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752348 TI - [Microalbuminuria in a population of 653 patients with type 1 and 2 diabetes]. AB - The aim of this retrospective study was to evaluate the prevalence of microalbuminuria in type 1 and 2 diabetic patients with or without high blood pressure levels. 653 patients were involved in the study [type 1: n = 413 (normotensive: n = 298; hypertensive: n = 115); type 2: n = 240 (normotensive: n = 93; hypertensive: n = 147)]. In type 1 diabetic patients, the prevalence of microalbuminuria was of 21 per cent. Microalbuminuria was also found in 28 per cent of type 2 diabetic subjects (p less than 0.10 vs type 1). The prevalence of microalbuminuria was significantly higher in hypertensive than in normotensive diabetic subjects (28 vs 20 per cent; p less than 0.05). Blood pressure in type 1 and 2 normotensive patients was significantly higher in subjects with than without microalbuminuria. We also observed higher HbA1 levels in microalbuminuric type 1 diabetic patients. Finally, we also assessed that the prevalence of diabetic chronic complications was higher in type 1 patients with than without microalbuminuria (p less than 0.05). This relationship was not evidenced in type 2 diabetic patients. In conclusion, the prevalence of microalbuminuria in a population of type 1 and 2 diabetic patients is high. We confirm in this study the relationship between microalbuminuria, blood pressure, and HbA1. PMID- 1752349 TI - Accuracy of blood glucose self monitoring in elderly insulin treated diabetic patients. AB - We investigated the accuracy of blood glucose self monitoring in 131 patients (mean +/- SD age 65 +/- 7 years, duration of diabetes 11 +/- 6 years) who participated in a 5-day inpatient group treatment and teaching programme especially designed for elderly insulin-treated patients. Patients' estimations and laboratory blood glucose measurements were compared on day 1 (after theoretical and practical introduction into blood glucose self monitoring) and on day 4 of the programme. Patients were trained in the visual reading of Haemoglukotest 20-800R; blood glucose meters were recommended only exceptionally. Error grid analysis showed a high accuracy of visually assessed blood glucose values, both on day 1 (94% of measurements in zone A, 5% in zone B) and on day 4 (95% in zone A, 4% in zone B). Patients with no prior experience in blood glucose self monitoring (n = 67) showed a significant improvement (p less than 0.02) in accuracy from day 1 to day 4. Values determined by blood glucose meters were less accurate, although this trend did not reach statistical significance. A second group of 94 consecutive patients was reexamined 5 years after participation in the treatment and teaching programme. 55 patients were still alive and 42 could be evaluated. Accuracy of blood glucose estimations was assessed in all 26 patients practising blood glucose self monitoring (age 69 +/- 5 years, diabetes duration 18 +/- 8 years), either at their homes (n = 23) or at our diabetes outpatient clinic (n = 3). Error grid analysis showed a high accuracy by visual reading (n = 21, 95% zone A, 5% zone B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752350 TI - Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non-insulin dependent diabetes by glucose tolerance test criteria. AB - The effect of metformin treatment was studied in nine patients with mild (fasting plasma glucose concentration less than 7.5 mmol.l-1) non-insulin-dependent diabetes mellitus (NIDDM) and fasting plasma triglyceride (TG) concentration greater than 2.0 mmol.l-1. Individuals were studied before and three months after receiving 2.5 g/day of metformin. Mean hourly plasma glucose concentration from 8 AM to 4 PM (7.5 +/- 0.5 vs 6.5 +/- 0.4 mmol.l-1, p less than 0.001), as well as glycosylated hemoglobin levels (7.0 +/- 0.5 vs 6.2 +/- 0.2%, p less than 0.02) were significantly lower following metformin treatment. The improvement in glycaemic control was not associated with an improvement in insulin stimulated glucose disposal as measured by the glucose clamp technique. Mean hourly day-long concentrations of plasma insulin (519 +/- 81 vs 364 +/- 64 pmol.l-1, p less than 0.001), FFA (502 +/- 45 vs 460 +/- 35 mu mol.l-1, p less than 0.01), and triglyceride (3.60 +/- 0.33 vs 3.02 +/- 0.31 mmol.l-1, p less than 0.001) concentrations were significantly lower following three months of metformin treatment. Finally, fasting plasma TG concentration, very low density lipoprotein (VLDL)-TG, and VLDL-cholesterol concentrations were significantly decreased, while high density lipoprotein (HDL)-cholesterol concentration was significantly increased following metformin therapy. Thus, metformin administration to individuals with NIDDM, who did not have significant fasting hyperglycaemia, led to a decrease in plasma glucose, insulin, FFA, and TG concentration, and an increase in plasma HDL-cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752351 TI - [Non-pharmacological interventions in the treatment of arterial hypertension associated with diabetes]. PMID- 1752352 TI - Age-related differences in sensory conditioning in rats. AB - Four experiments tested rats 8, 12, or 21 days postnatal for sensory conditioning in terms of the association acquired between two odors presented simultaneously or sequentially. The sensory conditioning of 8- and 12-day-old rats exceeded that of rats 21 days of age when the odors were presented simultaneously. When one odor was presented immediately followed by another, however, 21-day-old rats conditioned as effectively as the younger animals, and with a sufficiently long interval between odors (20 min), the sensory conditioning of the 21-day-old rats surpassed that of the rats 12 days of age. Although consistent across a variety of procedures, in previous experiments and within the present study, the age related differences in sensory conditioning after simultaneous presentation of two odors are difficult to understand. Increasing knowledge of the ontogeny of orienting may lead to an explanation in terms of Thompson's (1972) theory linking sensory conditioning with orienting and sensitization. PMID- 1752353 TI - A refractory period for the heart rate response in infant visual attention. AB - A refractory period for the heart rate (HR) response of 14-, 20-, and 26-week-old infants to second stimulus onset and primary stimulus offset during termination of visual attention was investigated. A stimulus that elicited a significant HR deceleration was presented. Following the return of HR to prestimulus level, a second stimulus occurred or the first stimulus ended at time delays of 0, 3, 6, and 9 s. If the second stimulus occurred at 0 or 3 s after HR returned to its prestimulus level, the HR response was smaller than the initial HR orienting response (OR). A usual HR OR resulted by waiting 6-9 s after the return of HR to prestimulus level. A significant offset response occurred only for the 6-sec delay. Active inhibition of vagal cardiac activity during attention termination may cause the observed refractory period in the HR response, which appears to last from 3-6 s following sustained attention. PMID- 1752354 TI - Prenatal stress effects on exploratory activity and stress-induced analgesia in rats. AB - Pregnant rats were exposed three times daily to immobilization stress during gestational Days 15-19. The behavior of their offspring was compared with the behavior of offspring from unstressed control mothers. Although the stress procedure decreased the weight gain of mothers during pregnancy, it slightly but significantly increased the weight of their offspring at birth and at weaning. On postnatal Day 10, prenatally stressed pups returned to their home cage more quickly than did prenatally unstressed control pups during a nest odor discrimination task, but no differences between groups in the number of correct responses were found. On postnatal Days 70-72, prenatally stressed offspring showed increased exploratory activity in a complex tunnel maze compared with control offspring. On postnatal Day 80, analgesia induced by stress (swimming for 3 min in cold water) was determined (tail flick latency). The degree of stress induced analgesia was smaller in prenatally stressed rats than in control rats. These data suggest that the effects of prenatal stress on behavior are most clearly discernable when such animals are confronted with a novel or stressful situation. PMID- 1752355 TI - The human genome initiative. PMID- 1752356 TI - Mozart, Alexander the Great, and the animal rights/liberation philosophy. PMID- 1752357 TI - Cellular desiccation and hydration: developmentally regulated proteins, and the maturation and germination of seed embryos. AB - Little more than a decade ago, 2-dimensional mapping of proteins and biochemical study of their allied coding elements (mRNA and DNA) were first used to probe possible changes in the embryo during seed germination. Because specification was of primary importance, our attention was initially directed toward the characterization of individual proteins and coding elements which, in preliminary surveys of the germinating wheat embryo, were found to be conspicuously subject to developmental regulation. Three of the proteins have become subjects of comprehensive investigations in this and other laboratories: the Em protein, the Ec protein, and germin. The Em and Ec proteins are encoded by the conserved mRNA 'stored' in the mature embryos of dry, field-ripened seeds but germin is encoded by the nascent mRNA formed after mature embryos are germinated in water. The Ec protein is the only bona fide Zn metallothionein yet found in higher plants. Studies of their biology and molecular biology suggest that the Em protein has a role in hormone-mediated (abscisic acid) cellular desiccation and that germin has a role in hormone-mediated (auxin) cellular hydration. It is projected that further studies of the Em protein may help elucidate the molecular basis for a loss of dessication tolerance during germination, and that further studies of germin may help elucidate the molecular basis of plant cell enlargement. PMID- 1752358 TI - Enzymatic control of pigmentation in mammals. AB - Visible pigmentation in mammals results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. The melanins are produced in melanocytes and can be of two basic types: eumelanins, which are brown or black, and phaseomelanins, which are red or yellow. In mammals typically there are mixtures of both types. The most essential enzyme in this melanin biosynthetic pathway is tyrosinase and it is the only enzyme absolutely required for melanin production. However, recent studies have shown that mammalian melanogenesis is not regulated solely by tyrosinase at the enzymatic level, and have identified additional melanogenic factors that can modulate pigmentation in either a positive or negative fashion. In addition, other pigment-specific genes that are related to tyrosinase have been cloned which encode proteins that apparently work together at the catalytic level to specify the quantity and quality of the melanins synthesized. Future research should provide a greater understanding of the enzymatic interactions, processing, and tissue specificity that are important to pigmentation in mammals. PMID- 1752359 TI - Androgen resistance caused by mutations in the androgen receptor gene. AB - Defects in the human androgen receptor cause a spectrum of defects in male phenotypic sexual development associated with abnormalities in the receptor protein assayed in cultured fibroblasts and in broken cell assays. In some patients these abnormalities are associated with absent ligand binding, in other qualitative or quantitative abnormalities of ligand binding are present, and in some no abnormality of ligand binding is detected. Analysis of the androgen gene structure in such patients has permitted identification of the causative mutation in many families. Although results of these studies often reinforce concepts established by in vitro mutagenesis studies of other steroid receptors, some mutations have provided unusual insight into the structural organization of the androgen receptor molecule. PMID- 1752360 TI - Site-specific recombination in the immune system. AB - Site-specific DNA recombination has been identified in a wide variety of biological systems. In vertebrates, however, the only identified use of this genetic device is in the immune system. Here it plays a critical role in generating a diverse repertoire of surface receptors to intercept invading microbes and parasites. The mechanism and orchestration of this reaction are intriguing and are relevant to a broad array of related biological and biomedical issues. PMID- 1752361 TI - Regulation of enzyme activity in the cell: effect of enzyme concentration. AB - The rapid development in our understanding of the regulation of enzyme activity makes it a high priority to ascertain whether the behavior of purified enzymes reflects their functional characteristics in vivo. Enzyme concentration is usually the most significant difference between routine in vitro assays and in vivo conditions, as it is well known that many intracellular enzymes are present in vivo at much higher concentrations than used in vitro. Various procedures are suitable for kinetic analysis at physiological concentrations of enzyme. Those more frequently used have been cell permeabilization, the utilization of purified enzymes at concentrations close to the in vivo range, and the addition of polyethylene glycol to increase the local protein concentration. In this review we briefly summarize observations on enzymes reported to exhibit concentration dependent activity. The effect of enzyme concentration has been most thoroughly investigated in the case of phosphofructokinase. These studies may provide insight into the regulation of this important enzyme in the cell. The implications of both homologous and heterologous protein-protein interactions for the effect of enzyme concentration and their roles in the control of enzyme activity in vivo are also discussed. PMID- 1752362 TI - Signal transduction in erythropoiesis. AB - The polypeptide hormone erythropoietin (Ep) is a growth factor whose actions on the erythroid progenitor cell induce proliferation and differentiation. The signal transduction system activated by Ep to mediate these cellular processes remains largely uncharacterized despite many years of research devoted to its elucidation. It is clear that an Ep receptor-mediated activation of adenylate cyclase or guanylate cyclase does not occur, although cAMP and cGMP may play modulatory roles. The role of calcium in the action of Ep is less clear. Although the presence of extracellular calcium seems to be an absolute requirement for Ep induced proliferation, the positive changes induced by Ep in intracellular calcium occur with a time course suggestive of influx through ion channels opening within the cell membrane rather than release of intracellular stores by inositol trisphosphate. There is good evidence for the involvement of phospholipases A2 and C in the actions of Ep, including an early rise in lipoxygenase metabolites of arachidonic acid. Activation of phospholipase C can also result in the activation of protein kinase C in response to Ep. We present a model for the signal transduction pathway of Ep that is consistent with current knowledge and provides a framework for the coordinate actions of several intracellular mechanisms in the mediation of Ep-induced proliferation. PMID- 1752363 TI - Vomeromodulin, a putative pheromone transporter: cloning, characterization, and cellular localization of a novel glycoprotein of lateral nasal gland. AB - Vomeromodulin, a novel glycoprotein of lateral nasal gland, has been cloned by differential hybridization from nasal/olfactory tissue. The 2.2-kb mRNA directs the in vitro synthesis of a 60-kDa primary translation product in reticulocyte lysates. Differential sensitivity to endoglycosidases indicates that vomeromodulin is posttranslationally modified in vivo by N-glycosylation to form a 70-kDa glycoprotein of the complex type. Immunocytochemical localization with two different antipeptide antisera demonstrates that vomeromodulin is abundant in the lateral nasal glands and is also present in the posterior septal and vomeronasal glands. Most striking is the observation that it is highly concentrated in the mucus of the vomeronasal organ of Jacobson but is not detectable in the mucus of the main olfactory neuroepithelium. Evaluation of mRNA and protein distribution by Northern and Western analyses, respectively, indicates that vomeromodulin is absent from 15 other tissues. The glandular and mucosal distribution of this glycoprotein implies a transport function that may be related to the mechanisms by which pheromones of low volatility gain access to their receptors in the vomeronasal organ. These observations support our hypothesis that vomeromodulin participates in perireceptor events that facilitate the process of pheromone access and detection. PMID- 1752364 TI - Transgenic animals in biomedical research. AB - The advent of transgenic technology, in which foreign genetic information is stably introduced into the mammalian germ line, has dramatically enhanced our basic knowledge of physiologic and pathologic processes. Transgenic animals created by these genetic manipulations are being used to provide insights into gene regulation, development, pathogenesis, and the treatment of disease. Furthermore, transgenic biotechnology holds great promise for the creation of genetically superior livestock and the industrial production of precious pharmaceuticals. It is evident now that the study and use of transgenic animals will significantly improve the human condition. PMID- 1752365 TI - Early choline research and the aftermath. PMID- 1752366 TI - Relationship between interferon-gamma, indoleamine-2,3-dioxygenase and tryptophan. PMID- 1752367 TI - Regulating body mass. PMID- 1752368 TI - [Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France]. AB - The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products. PMID- 1752369 TI - [Appendectomy, cholecystectomy, cholelithiasis and colorectal cancer. A retrospective case control study at the Cote-d'Or]. AB - Several studies have shown that there might be a relationship between previous history of appendectomy or cholecystectomy and the subsequent risk of colorectal cancer. In order to investigate these hypotheses, a case-control study was set up to compare the history of appendectomy and cholecystectomy as well as the presence of cholelithiasis in patients with colorectal carcinoma vs patients with gastric carcinoma. The study was performed in the 727 patients included in the Registry of Digestive Cancers of the Cote d'Or and treated at the Dijon University Hospital during the period 1981-1987. These patients were well matched to those of the whole registry population for sex, age, stage, and residence distributions. In females, in comparison to the gastric cancer patients, a personal history of appendectomy was more commonly observed in case of right colonic cancer (odds ratio: 3.5; P less than 0.01) and a personal history of cholecystectomy in case of left colonic cancer, in particular when considering only those earlier than 10 years (odds ratio: 3.2; P less than 0.05). In contrast, the risk of rectal cancer was lower in case of a cholecystectomy performed more than 10 years earlier (odds ratio: 0.2; NS) and in case of cholelithiasis (odds ratio: 0.4; P less than 0.05). In males, there was no difference between cases and controls as for the proportion of appendectomies, cholecystectomies or cholelithiasis. These observations are consistent with the hypothesis that the appendix as a lymphoid organ plays a protective role in colon carcinogenesis, in particular in women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752370 TI - [Does chronic pancreatitis promote duodenal ulcer in men?]. AB - The aims of this study were to assess the prevalence of duodenal ulcer during chronic pancreatitis and the relationship between the occurrence of duodenal ulcer and the course of chronic pancreatitis. The population consisted of 264 men with chronic pancreatitis, 94 percent of which were of alcoholic origin. Duodenal ulcer occurred in 37 patients (14 percent). Fifteen patients with gastric or anastomotic ulcer were excluded. The 37 patients with duodenal ulcer were compared with 212 patients without ulcer. There was no significant difference between the two groups as regards the course of chronic pancreatitis except for insulin-dependent diabetes mellitus which was significantly more frequent in patients without duodenal ulcer (P less than 0.05). Eight patients with duodenal ulcer died but the cause of death was not related to their ulcer. All patients with duodenal ulcer and 92 percent of those without were smokers (not significant). Duodenal ulcer occurred in 25/37 patients (68 percent) before the clinical onset of chronic pancreatitis. The risk of duodenal ulcer occurrence was constant in 17-65 year old patients and independent of the time of chronic pancreatitis onset. We concluded that in men with chronic pancreatitis: a) prevalence of duodenal ulcer is 14 percent; b) duodenal ulcer occurred most often before clinical onset of chronic pancreatitis; c) duodenal ulcer occurs independently of the course of pancreatitis which cannot account for its high prevalence. Smoking may be a promoting factor. PMID- 1752371 TI - [Antibiotic-induced gastrointestinal side effects]. PMID- 1752372 TI - [Treatment of chronic hepatitis C with interferon alpha]. PMID- 1752373 TI - Efficacy of long term recombinant interferon-alfa in patients with chronic hepatitis C. A clinical, biological, histological and immunohistological study. AB - A prospective, non randomized trial was conducted in 22 patients with chronic hepatitis C treated for 6 months with interferon-alfa at the dose of 3 million units three times a week followed by decreasing doses for the following 6 months. Transaminase activity measurements were taken at 2, 6, 12, 18, and 24 months and a liver biopsy was performed at zero and 6 months to assess efficacy. Immunohistochemical study of HLA class I and lymphocyte subsets was performed on the biopsy specimen before and after 6 months of treatment. A complete biological response was observed in 82, 82, 60, 64 and 70 percent of patients at 2, 6, 12, 24 and 36 months, respectively. Four patients relapsed including 2 patients who suddenly stopped taking interferon-alfa. An improvement of histological features was observed in 90 percent of patients for necrosis and in 80 percent of patients for inflammation, with an overall improvement in Knodell's score reaching 85 percent. Immunohistochemical studies showed CD8+ cell infiltration already present in the area of necrosis before treatment. These tests also showed that HLA class I expression by the hepatocyte membranes was increased at 6 months and was identical in patients with or without histological improvement. PMID- 1752374 TI - [Rejection in liver transplantation]. PMID- 1752375 TI - [Polypoid pseudosarcomatous carcinoma of the esophagus. Report of two cases with favorable outcome after medical treatment]. AB - The authors report two cases of esophageal polypoid pseudosarcoma with favorable outcome after endoscopic and medical treatment. Neither of the two patients could undergo general anesthesia. Endoscopic resection or monopolar electrocoagulation of the tumor was associated with chemotherapy and radiation therapy. A complete response of the tumor was observed in both cases. The two patients were alive and well with no evidence of recurrence or metastasis 3 and 5 years after diagnosis. Immunohistochemical study of those two tumors with monoclonal antibodies to intermediate filaments (keratin and vimentin) suggests duality in the spindle cell component. It may explain the biological behaviour of these particular cancers that have a better prognosis than other types of squamous cell carcinomas of the esophagus. PMID- 1752376 TI - [Analysis of the activities (1985-1991) of the doctoral thesis "Cellular and Functional Biology of Digestion"]. PMID- 1752377 TI - [Successful treatment of fulminant Crohn's colitis with azathioprine]. PMID- 1752378 TI - Pitfalls in graphical display of 24-hour pH measurement. PMID- 1752379 TI - [Efficacy of ursodeoxycholic acid in the treatment of duodenogastric reflux in the antrectomized patients]. PMID- 1752380 TI - [Efficacy of high level cholestyramine therapy in radiation-induced hemorrhagic proctitis]. PMID- 1752381 TI - [Acute hemorrhagic colitis related to oral administration of cephalosporin]. PMID- 1752382 TI - [Fulminant hepatitis probably induced by medifoxamine (Cledial)]. PMID- 1752383 TI - [Ascariasis: an unusual cause of cholangitis in our climate]. PMID- 1752384 TI - [Granulomatous hepatitis following intravesical BCG immunotherapy for cancer of the bladder]. PMID- 1752385 TI - [Surgical treatment of Barrett esophagus]. PMID- 1752386 TI - [Adjuvant treatment of resected colon cancers using a 5-fluorouracil-levamisole combination]. PMID- 1752387 TI - [Prevention of post-transfusion hepatitis non-A, non-B. Report established by the National Agency for the Development of Medical Evaluation on demand of the General Health Direction]. PMID- 1752388 TI - Manometric evaluation of esophageal function in progressive systemic sclerosis with special regard to the disease severity. AB - A study was conducted to elucidate the relation between the severity of progressive systemic sclerosis (PSS) and the grade of esophageal function disorder, the extent of which was estimated using esophageal manometry. Fifty two patients with PSS were divided into the mild, moderate and severe groups according to the severity score established by the PSS Research Group supported by The Ministry of Health and Welfare of Japan. Primary peristaltic pressure in the esophageal body at 25 to 35cm from the incisors as well as lower esophageal sphincter pressure (LESP), which represents the function of the smooth muscle of the esophagus, were significantly decreased in parallel with the increasing severity of PSS. In contrast, there was no significant difference in upper esophageal sphincter pressure (UESP) or in primary peristaltic pressure at 20cm from the incisors, indicating that the function of striated muscle of the esophagus was not impaired. In addition, even in the mild PSS group without dysphagia (19 cases), primary peristaltic pressure in the esophageal body at 25 to 35cm from incisors was found to be significantly decreased in comparison with the control. Hence, esophageal manometry was useful for early detection of the pathophysiological state of the esophageal function in PSS. PMID- 1752389 TI - A new method of separation and quantitation of mucus glycoprotein in rat gastric mucus gel layer and its application to mucus secretion induced by 16,16-dimethyl PGE2. AB - A method was established for recovering the mucus gel layer of rat gastric mucosa without damage to underlying surface epithelium. The mucus gel was solubilized by stirring the gastric mucosa in a solution of N-acetylcysteine (NAC), a mucolytic agent. Optimal mucus gel solubilization was possible by treatment with 2% NAC for 5 minutes at room temperature. Mucus glycoprotein was quantitatively extracted and measured from the mucus gel sample obtained by the NAC treatment. This treatment caused no damage to surface epithelial cells, as observed by a light microscope. Besides NAC, pronase solution was also adequate for solubilizing the mucus gel layer without any damage to the surface epithelium. However, extraction and measurement of mucus glycoprotein from the pronase-treated mucus gel sample was not possible due to contamination by high molecular hexose-containing substances which were eluted along with the mucus glycoprotein from the column of Bio-Gel A-1.5m. This NAC method was used to examine changes in mucus glycoprotein content in the mucus gel at one hour following the oral administration of 16,16 dimethyl prostaglandin E2. A significant increase in mucus glycoprotein of the gel was brought about by the prostaglandin treatment. Thus, the present method was suitable for estimating the amount of mucus secreted in to the mucus gel layer. PMID- 1752390 TI - Advanced gastric cancer of the antrum: anatomic-functional correlation between chief cell mass and serum pepsinogen I. AB - Chief cell mass and type I serum pepsinogen (PGI) were calculated in 19 advanced antral gastric cancer of intestinal type. Comparisons were also made with parietal cell mass and acid secretion. In gastric cancer of the antrum there is a significant decrease of the chief cell mass and of serum pepsinogen I. The patients were subdivided according to the histological findings of the fundic mucosa. In cases of antral gastric cancer with superficial fundic gastritis there is normozymogenism with hyperpepsinogenemy; with preatrophic fundic gastritis there is hypozymogenism with normopepsinogenemy; with atrophic fundic gastritis there is hypozymogenism with hypopepsinogenemy. Similar behavior of the chief cell mass between antral gastric cancer and fundic atrophic gastritis without cancer has become recognized and while the validity of PGI as a marker of fundic atrophic gastritis has emerged it does not allow discrimination between atrophic fundic gastritis and atrophic fundic gastritis associated with gastric cancer of the antrum. PMID- 1752391 TI - 2',5' Oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during interferon treatment of chronic non-A, non-B hepatitis. AB - The 2'-5' oligoadenylate synthetase (2-5 AS) activity of peripheral blood mononuclear cells and serum was measured in 23 patients with chronic non-A, non-B hepatitis during interferon therapy, 16 of whom were found to have antibody to hepatitis C virus (anti-HCV). Patients received a daily dose of either 1 million, 3 million or 6 million units of human interferon-alpha or -beta for 4 to 6 weeks. Before treatment, the 2-5 AS activity was not significantly different from that in normal control subjects or patients with chronic hepatitis B. However, during treatment the 2-5 AS activity increased 2- to 41-fold from the initial level. Alanine aminotransferase (ALT) levels normalized promptly after the start of treatment in 15 (65.2%) of the 23 patients, but remained elevated in the remaining 8 (34.8%). Six (40%) of the 15 patients showed consistently normal ALT levels for 6 to 30 months after the end of treatment. There was no significant difference between the responders and non-responders in the pattern of change of 2-5 AS activity, but pretreatment activity levels in peripheral blood mononuclear cells were significantly higher (P less than 0.001) in the patients whose ALT levels did not normalize during treatment. The frequency of patients with a positive anti-HCV was significantly higher (P less than 0.05) in the group in which ALT levels normalized. Therefore, these findings suggest that the pretreatment 2-5 AS activity and the detection of anti-HCV may be useful parameters for predicting the response to interferon therapy. PMID- 1752392 TI - Beneficial effects of fructose-1,6-diphosphate infusion on liver regeneration after ischemic liver injury. AB - The effect of fructose-1,6-diphosphate (FDP) on cellular viability after partial hepatectomy in partial ischemic liver was investigated in rats. The administration of FDP did not increase blood flow in the hepatic tissue; however, it significantly suppressed the elevation of serum liver functions for 24 hours after partial hepatectomy. Levels of DNA synthesis, protein synthesis, and labeling index were significantly higher in the groups administered divided doses of FDP before and after partial hepatic ischemia than in the control group (P less than 0.01). Thus, these findings indicate that FDP has cytoprotective and hepatotrophic effects on liver with ischemic injury and that divided dose administration of FDP is more effective than bolus doses in decreasing damage following ischemic and reperfusion injury. PMID- 1752393 TI - Photodynamic therapy using pheophorbide-a and Q-switched Nd:YAG laser on implanted human hepatocellular carcinoma. AB - To evaluate whether administration of pheophorbide-a, a new photosensitizer, followed by use of Q-switched Nd:YAG laser produces a photodynamic reaction, we administered pheophorbide-a to female nude mice (BALB/c-nu) that had been implanted with human hepatocellular carcinoma. Intra-tumoral concentrations of pheophorbide-a were measured by high-performance liquid chromatography. 3 hours after peroral administration of 1 mg/kg body weight, the intra-tumoral concentration was too low to reveal photodynamic effects. Peroral administration of 250 mg/kg body weight, intra-peritoneal administration of 5 mg/kg body weight, and intra-tumoral injection of 200 micrograms yielded 0.24 micrograms/g, 0.83 micrograms/g and 3.68-108 micrograms/g tumor concentrations, respectively. All tumors were irradiated interstitially using a Q-switched Nd:YAG laser at 1064 nm. Only tumors that had been intra-tumorally injected had areas of necrosis larger than those in control tumors. The results suggest that the injection of pheophorbide-a followed by interstitial irradiation using a Q-switched Nd:YAG laser does not induce sufficient photodynamic reaction if the intra-tumoral pheophorbide-a concentration is less than 0.83 micrograms/g tumor tissue, and that photodynamic therapy may be useful if the pheophorbide-a tumor concentration is within the range of 0.83-108 micrograms/g. PMID- 1752394 TI - Novel high-performance liquid chromatography for determination of membrane phospholipid composition of rat hepatocytes. AB - We have developed a new, quick and efficient method of high-performance liquid chromatography (HPLC) for the isolation and quantitative determination of phospholipids in hepatocyte membranes. A silica gel column was used for the isolation and determination, and an isocratic mixture of acetonitrile, methanol and 85% phosphoric acid (130:5:1.7, v/v/v) was used as a mobile phase. Six kinds of phospholipids, i.e. phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphinogomyelin (SPH), in this order, were completely isolated within 45 min. The phospholipid composition of sinusoidal membrane vesicles (SMV) and canalicular membrane vesicles (CMV) obtained from rat liver, as well as of human erythrocyte ghosts were determined by this HPLC method. The level of SPH in CMV was significantly higher than that in SMV, and the level of PC in CMV was significantly lower than that in SMV. These results were considered attributable to the low fluidity of CMV. The phospholipid composition of human erythrocyte membrane was different from that of rat SMV and CMV. The present technique is suitable for quantitative determination of phospholipids in cell membranes. PMID- 1752395 TI - Experimental study on the pathogenesis of acute acalculous cholecystitis, with special reference to the roles of microcirculatory disturbances, free radicals and membrane-bound phospholipase A2. AB - To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A2 (PLA2) activity, content of lipid peroxide, and superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PLA2 activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PLA2 activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PLA2. PMID- 1752396 TI - Histological changes of the gallbladder and liver after extracorporeal shock wave lithotripsy for gallbladder. AB - The histological changes of the gallbladder and liver following extracorporeal shock wave lithotripsy (ESWL) were investigated in a canine model. After performing ESWL on human cholesterol stones placed in the gallbladder of 8 dogs, the gallbladder and livers were removed for pathological study. The mucosa of the gallbladder showed erosion and ulceration in three of the eight dogs. Edema and bleeding were found in the stroma of the gallbladder beds. Hemorrhagic necrosis and vacuolar degeneration occurred in liver parenchyma adjacent to the gallbladder bed, but the portal area was fairly well preserved. It can be said that ESWL caused damage to both the liver and the gallbladder, but its effects on the liver may be only slight because of the preservation of the portal area. PMID- 1752397 TI - Multiple diffuse hemangiomas of the large intestine. AB - A 54-year-old male case with multiple, diffuse hemangiomas of the large intestine is described. Large diffuse hemangiomas were located at the rectosigmoid and the ascending colon. Some polypoid lesions were located on the transverse colon. Tiny calcifications representing phleboliths were detected in those lesions. No skin hemangiomas were present. Although he did not manifest systemic bleeding tendency, blood examinations demonstrated the presence of mild consumption coagulopathy. PMID- 1752398 TI - A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years. AB - A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver. PMID- 1752399 TI - Insemination of bile duct carcinoma to the liver after insertion of percutaneous biliary endoprosthesis. AB - Percutaneous transhepatic biliary drainage is widely used to relieve bile duct obstruction which can be caused by bile duct or pancreas carcinomas. Although the incidence is low, insemination of carcinoma along the transhepatic catheter tract is considered to be a serious complication of percutaneous transhepatic biliary drainage. The authors present a case of intrahepatic insemination of bile duct carcinoma along the catheter that subsequently underwent a curative resection consisting of pancreaticoduodenectomy and right hepatic lobectomy. It is suggested that a percutaneous biliary endoprosthesis through the tumor should be avoided in patients in whom a possible curative resection can be considered. External biliary drainage should only be performed in order to minimize the manipulation of the tumor in such patients. PMID- 1752400 TI - Expression of heat shock protein in human gastric mucosa. PMID- 1752401 TI - A solid-phase enzyme-linked immunospot (ELISPOT) assay for detection of Helicobacter pylori antibody-producing cells in gastric mucosa. PMID- 1752402 TI - Behcet's disease. PMID- 1752403 TI - [Study of the effectiveness of artificial oxygen carrier on the hemoglobin base in blood loss replacement in dogs]. AB - The effectiveness of modified polyhemoglobin proposed as an artificial oxygen carrier (AOC) was evaluated in experiments on dogs with acute fatal hemorrhage. It was shown that total oxygen consumption, arterial blood pressure and circulating blood volume were maintained at the normal physiological levels during 4 h after infusion of 10% solution of polyhemoglobin. AOC infusion provided 100% survival of the animals. It has been concluded that hemoglobin polymer modified with pyridoxal-5'-phosphate can be used as the basis for the production of the medicinal form of AOC. PMID- 1752404 TI - [The oxygen system of an isolated heart during its perfusion with a suspension of human erythrocytes after different periods of their preservation in a solution containing adenine]. AB - Seven series of experiments (68 tests) were conducted on an isolated rat heart with the functioning left ventricle during its coronary vessels perfusion with suspension of human erythrocytes of different storage terms preserved in the solution containing citroglucophosphate with adenine. The main parameters of hemodynamics and oxygen regimen were evaluated. The results of the study have shown that washed human donor erythrocytes preserved in the above solution after 1, 7, 14, 21 and 28 days of storage present a highly efficient gas-carrying medium under conditions of acute anemic hypoxia. PMID- 1752405 TI - [Quantitative, functional and cytogenetic characteristics of lymphocytes and various indicators of immunity in persons participating in the decontamination work at the Chernobyl nuclear power plant]. AB - Immunologic and cytogenetic investigations conducted in subjects, who had been engaged in liquidation of consequences of the Chernobyl NPS catastrophe, during the first months after their work was finished, showed decreased content of large granulo-containing lymphocytes and serum IgM in the blood, their levels were completely recovered 3 years later. A complex of unfavourable factors attending radiation (stress, changes in the way of life, chemical actions etc.) played an important role in the genesis of these changes. PMID- 1752406 TI - [Cell line regulation in hematopoiesis]. PMID- 1752407 TI - [Plasma cell myeloma. I. A new concept of disease biology]. PMID- 1752408 TI - [Cell number in the medullary substance of hair: a simple and sensitive indicator of exposure to radiation]. AB - The medulla of the lower regions of a growing mouse hair contains a very regularly spaced column of cell nuclei. The total number of nuclei 3 days after irradiation in this column (from its lower recognition point to the point of terminal differentiation and nuclear degradation) proves to be a sensitive indicator of the level of radiation exposure. PMID- 1752409 TI - [Transduction of oncogene RAS into antibody-producing hybridoma]. AB - The effect of introduction by means of electroporation of protogene ras into cells of antibody-producing hybridoma was studied. Doubling time (TD) of transduced subclones, in which H-ras gene was expressed, proved to be 1.8-fold shorter as compared to the parent line. Other characteristics of the hybridoma (cloning efficiency, antibody production in vitro, the time of ascitic fluid appearance in mice and antibody titer in vivo) were not changed. Addition of 12-0 tetradecanoylphorbol acetate to the culture did not alter the growth parameters of H-ras transduced subclones. PMID- 1752410 TI - Qualitative and quantitative genetic studies of Arabidopsis thaliana. PMID- 1752411 TI - Pseudoreversion analysis indicates a direct role of cell division genes in polar morphogenesis and differentiation in Caulobacter crescentus. AB - A pseudoreversion analysis was used to examine the role of cell division genes in polar morphogenesis in Caulobacter crescentus. Extragenic suppressors of temperature sensitive mutations in pleC, a pleiotropic gene required for cell motility, formation of polar phi CbK bacteriophage receptors, and stalk formation, were isolated. These suppressors, which restored motility at 37 degrees C, simultaneously conferred a cold sensitive cell division phenotype and they were mapped to the three new cell division genes divJ, divL and divK. The cold-sensitive mutations in divL, and to a lesser extent divJ, exhibited a relatively narrow range of suppression. The cold-sensitive cell division mutation in divK, by contrast, suppressed all pleC mutations examined and behaved as a classical bypass suppressor. The direct role of this cell division gene in the regulation of motility is suggested by the observation that divK341 mapped to the same locus as pleD301, a pleiotropic mutation that prevents loss of motility and stalk formation. These results provide strong evidence that the cell division and developmental pathways are interconnected and they support our earlier conclusion that cell division is required for the regulation of polar morphogenesis and differentiation in C. crescentus. PMID- 1752412 TI - Seven-base-pair inverted repeats in DNA form stable hairpins in vivo in Saccharomyces cerevisiae. AB - Palindromic sequences in single-stranded DNA and RNA have the potential for intrastrand base pairing, resulting in formation of "hairpin" structures. We previously reported a genetic method for detecting such structures in vivo in the yeast Saccharomyces cerevisiae. Below, we describe evidence indicating that a 14 base-pair palindrome (7 bp per inverted repeat) is sufficient for formation of a hairpin in vivo. PMID- 1752413 TI - New SNF genes, GAL11 and GRR1 affect SUC2 expression in Saccharomyces cerevisiae. AB - To identify new genes required for depression of the SUC2 (invertase) gene in Saccharomyces cerevisiae, we have isolated mutants with defects in raffinose utilization. In addition to mutations in SUC2 and previously identified SNF genes, we recovered recessive mutations that define four new complementation groups, designated snf7 through snf10. These mutations cause defects in the derepression of SUC2 in response to glucose limitation. We also recovered five alleles of gal11 and showed that a gal11 null mutation decreases SUC2 expression to 30% of the wild-type level. Finally, one of the mutants carries a grr1 allele that converts SUC2 from a glucose-inducible gene. PMID- 1752414 TI - SUM1-1: a suppressor of silencing defects in Saccharomyces cerevisiae. AB - The repression of transcription of the silent mating-type locus HMRa in the yeast Saccharomyces cerevisiae requires the four SIR proteins, histone H4 and a flanking site designated HMR-E. The SUM1-1 mutation alleviated the need for many of these components in transcriptional repression. In the absence of each of the SIR proteins, SUM1-1 restored repression in MAT alpha strains; thus, SUM1-1 appeared to bypass the need for the SIR genes in repression of HMRa. Repression was not specific to the genes normally present at HMR, since the TRP1 gene placed at HMR was repressed by SUM1-1 in a sir3 strain. Therefore, like the mechanisms of silencing normally used at HMR, silencing by SUM1-1 was gene-nonspecific. SUM1 1 suppressed point mutations in histone H4, but failed to suppress strongly a deletion mutation in histone H4. Similarly, SUM1-1 suppressed mutations in the three known elements of HMR-E, but was unable to suppress a deletion of HMR-E. These epistasis analyses implied that the functions required for repression at HMR can be ordered, with the SIR genes and silencer elements acting upstream of SUM1-1. SUM1-1 itself may function at the level of chromatin in the assembly of inactive DNA at the silent mating-type loci. PMID- 1752415 TI - Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. AB - We have isolated a snf1/ccr1 mutant of Saccharomyces cerevisiae which loses viability upon starvation and fails to accumulate glycogen in response to abrupt depletion of phosphate or glucose. A snf1 null mutant is sensitive to heat stress and starvation and fails to accumulate glycogen during growth in rich medium. The phenotypes of the snf1 mutants are those commonly associated with an overactivation of the adenylate cyclase pathway. Mutations in adenylate cyclase or RAS2 which decrease the level of cAMP in the cell moderate the snf1 phenotype. In contrast, a mutation in RAS2 (RAS2val19) which increases the level of cAMP or a mutation in the regulatory subunit (BCY1) of cAMP-dependent protein kinase which results in unregulated cAMP-dependent protein kinase activity accentuates the snf1 phenotype. However, the action of SNF1 in the stress response appears at least partly independent of cAMP-dependent protein kinase because a snf1 phenotype is observed in a strain that lacks all three of the genes that encode the catalytic subunits of cAMP-dependent protein kinase. SNF1 therefore acts at least in part through a cAMP-independent pathway. PMID- 1752416 TI - A mushroom-inducing DNA sequence isolated from the Basidiomycete, Schizophyllum commune. AB - A DNA sequence capable of inducing the de novo development of fruiting bodies (mushrooms) when integrated into the genome of unmated, nonfruiting strains of the Basidiomycete Schizophyllum commune has been isolated and partially characterized. This sequence, designated FRT1, overrides the normal requirement of a mating interaction for fruiting in this organism. It has been shown to integrate stably in different chromosome locations and appears to be trans acting. It also enhances the normal process of fruiting that occurs after mating. Additional DNA sequences with similarity to FRT1 were detected within the genome of the strain of origin by hybridization of labeled FRT1 DNA to blots of digested genomic DNAs. FRT1 and the genomic sequences similar to it were shown to be genetically linked. Southern hybridization experiments suggested sequence divergence at the FRT1 locus between different strains of S. commune. A testable model for how FRT1 may act as a key element in the pathway for the differentiation of fruiting bodies is presented as a working hypothesis for further investigation. PMID- 1752417 TI - Permanent rescue of a non-Mendelian mutation of Paramecium by microinjection of specific DNA sequences. AB - The mutant Paramecium tetraurelia cell line d48 is unable to express the serotype A protein on its surface. Although the A gene is intact in the micronuclei of d48, the A gene copies in the macronucleus contain a large deletion eliminating virtually the entire coding sequence. Previous studies showed that microinjection of a plasmid containing the entire A gene into the macronucleus of d48 permanently restored A expression after autogamy. Together with other data, this result suggests that in wild type cells the A gene in the old macronucleus ensures the presence of a cytoplasmic factor that prevents A gene deletions at autogamy. In d48, where there are few, if any copies of the intact A gene in the old macronucleus, deletions occur during macronuclear formation. To elucidate the specific molecular mechanisms involved in this unusual phenomenon, we attempted to define the region(s) of the A gene necessary for rescuing d48. We show that microinjection of a 4.5-kb internal A gene fragment is sufficient for proper processing at autogamy and leads to permanent rescue of d48; i.e., the rescued strain is indistinguishable from wild type. Thus, rescue of d48 does not require upstream transcriptional control sequences, intact A mRNA or A serotype protein. We also show that various fragments of the A gene have the ability to rescue d48 to different extents, some being more efficient than others. We find no evidence to suggest that the A gene gives rise to a small stable RNA that might act as or encode a cytoplasmic factor. Molecular mechanisms that may be involved in the rescue of d48 are discussed. PMID- 1752418 TI - Genetic analysis of a major segment [LGV(left)] of the genome of Caenorhabditis elegans. AB - From 10,900 F1 progeny of ethyl methanesulfonate (EMS)-mutagenized Caenorhabditis elegans nematodes, we isolated 194 lethal mutations on the left arm of LGV, a region balanced by the reciprocal translocation of eT1. The analysis of 166 of those mutations resulted in the identification of one deficiency and alleles of 78 genes including 38 new genes, thus increasing the number of identified essential genes to 101. We estimate that there are a minimum of 120 essential genes in this region, which comprises approximately 7% of the recombinational distance, although only about 4.2% of the genes, in C. elegans. We calculate that there are a minimum of 2850 essential genes in the genome. The left arm of LGV has two recombinational gene clusters separated by a high-recombination and/or essential gene-sparse region. One gene in this region, let-330, is the largest EMS target on the left arm of LGV, with twice as many alleles (16) as the next most EMS-mutable genes, let-332 and rol-3. Another gene in the sparse region, lin 40, and the region near lin-40 are major targets for Tc1 mobilization-induced mutagenesis. The analysis of essential genes in large regions should help to define C. elegans in terms of all its genes and aid in the understanding of the relationship of genome structure to genome function. PMID- 1752420 TI - Linkage disequilibrium analysis of chromosomal inversion polymorphisms of Drosophila. AB - The linkage disequilibrium pattern analysis is a method that allows one to detect present and past events of selection. We applied it to our data on the inversions of Drosophila mediopunctata and to published data of Drosophila subobscura, which are systems probably under complex modes of selection. The method gave meaningful results showing that it might be an excellent exploratory tool to identify problems worthy of further study. It is also suggested that it can be used as a criterion to determine the roots of inversion phylogenies. PMID- 1752419 TI - Analysis of sequences regulating larval expression of the Adh gene of Drosophila melanogaster. AB - The effects of a series of eight, 50 base pair internal deletions in the 5' region upstream of the proximal transcription start site of the Adh gene of Drosophila melanogaster were examined in a quantitative assay. Mixtures of two plasmids, one bearing a deleted gene, the other with an intact reference gene, were injected into alcohol dehydrogenase-negative embryos. Third instar larvae of the injected generation were assayed for relative alcohol dehydrogenase enzyme activity. Quantitative analysis of the eight deletions indicated that two regions were required for any detectable enzyme activity and one region was required for appropriate tissue specificity. The remaining five deletions significantly decreased, but did not eliminate activity. When the deleted genes were placed on a plasmid with an intact reference gene, activities of all but one deletion were restored to levels equivalent to that of the intact reference gene (regardless of orientation). This restoration of activity did not occur when the regulatory region of the intact gene was replaced with the Hsp70 heat shock promoter nor when the 50-base pair deletion encompassed the region that includes the TATA sequence. The fact that seven of the eight deleted genes express activity in the presence of a reference gene on the same plasmid suggests that the deleted gene is controlled by regulatory elements in the reference gene. Further, these regulatory elements exhibit no preference for their own, more proximate, promoter. PMID- 1752421 TI - The effect of DNA sequence polymorphisms on intragenic recombination in the rosy locus of Drosophila melanogaster. AB - The effect of simple DNA sequence polymorphisms on intragenic recombination in the rosy locus of Drosophila melanogaster was assayed. Two crosses were performed involving nearly identical molecular distances between selective ry null mutations (3778 nucleotides and 3972 nucleotides). In one heterozygote (ry606/ry531), in addition to the nucleotide substitution ry- mutations, there were 11 simple nucleotide polymorphisms between the selective markers as well as additional flanking simple nucleotide polymorphisms within the rosy locus. In the other heterozygote (ry606/ry609), there were no additional polymorphisms because the two rosy nucleotide substitution mutations were induced on the same rosy isoallele (ry+6). From ry606/ry531 heterozygous females, 27 intragenic crossovers and five marker conversions were seen among 4.53 x 10(5) progeny. From ry606/ry609 heterozygous females, 23 intragenic crossovers and eight marker conversions were seen among 4.18 x 10(5) progeny. The intragenic crossover frequencies per kilobase of DNA were very similar, 1.6 x 10(-5) for ry606/ry531 and 1.4 x 10(-5) for ry606/ry609. Thus, simple DNA sequence polymorphisms neither inhibit nor promote intragenic recombination in D. melanogaster. PMID- 1752422 TI - Embryonic head involution and rotation of male terminalia require the Drosophila locus head involution defective. AB - We have characterized the head involution defective (hid) locus which is located within the chromosomal region 75B8-C1,2. During the morphogenetic reorganization of the embryonic head region, hid+ function is necessary for the movement of the dorsal fold across the procephalon and clypeolabrum, a process that forms the frontal sac. The absence of the frontal sac in the hid mutant embryos affects the formation of the dorsal bridge and disrupts the development of the larval cephalopharyngeal skeleton. In addition to its embryonic role, this same hid function is also required during pupal development for the 360 degrees rotation of the male terminalia about the anterior-posterior body axis, and for a late step of wing blade morphogenesis. Although the abnormal wing phenotype caused by the Wrinkled (W) mutation is quite different from the one resulting from the loss of-function hid mutations, the characterization of EMS-induced W revertants reveals that W is actually an antimorphic allele of hid. PMID- 1752423 TI - Two genetically and molecularly distinct functions involved in early neurogenesis reside within the Enhancer of split locus of Drosophila melanogaster. AB - Molecular correlation of the genetic aspects of the function of the neurogenic gene Enhancer of split [E(spl)] has previously been hampered by the densely transcribed nature of the chromosomal region within which it resides. We present data indicating that two distinct molecular species contribute to E(spl) function. Analysis of new E(spl) alleles has allowed us to define two complementing functions within the locus. Subsequent phenotypic analysis of different E(spl) deficiencies combined with P element-transformed constructs has demonstrated that these two functions correspond to: (1) a family of helix-loop helix (HLH) protein-encoding genes and (2) the single copy gene E(spl) m9/10, whose product shares homology with G-protein beta subunits. The zygotically active E(spl) HLH genes can, at least partially, substitute for one another's functions and their total copy number determines the activity of the locus. E(spl) m9/10 acts synergistically with the E(spl) HLH genes and other neurogenic genes in the process of neurogenesis. The maternal component of E(spl) m9/10 has the most pronounced effect in neurogenesis, while its zygotic component is predominantly required during postembryonic development. The lethality of trans heterozygotes of null E(spl) deficiency alleles with a strong Delta point mutation is a result of the concomitant reduction in activity of both E(spl) HLH and m9/10 functions. Immunocytochemical localization of the E(spl) m9/10 protein has revealed that it is a ubiquitously distributed nuclear component in embryonic, larval and imaginal tissues. PMID- 1752424 TI - Molecular basis for allelic polymorphism of the maize Globulin-1 gene. AB - An abundant protein in maize (Zea mays L.) embryos is a storage globulin encoded by the polymorphic Glb1 gene. Several Glb1 protein size alleles and a null allele have been described. Here we report the isolation and nucleotide sequence analysis of genomic clones corresponding to two Glb1 size alleles (Glb1-L and Glb1-S) and to the Glb1-0 null allele. The Glb1-L and Glb1-0 alleles differ from Glb1-S by the presence of small nucleotide insertions which are imperfect or perfect duplications, respectively, of adjacent sequences. In the case of Glb1-L, the insertion is in-frame and results in a protein larger than that encoded by Glb1-S, whereas in Glb1-0 the insertion causes a translational frameshift which introduces a premature termination codon. Although steady-state levels of Glb1-0 transcripts are extremely low in Glb1-0/0 embryos, nuclear transcription assays indicate that the Glb1-0 gene is transcribed at a level comparable to that of Glb1-L. This suggests that the low amounts of Glb1-0 transcripts in the cytoplasm may be due to mRNA instability. PMID- 1752425 TI - Molecular analysis of the hot spot region related to length mutations in wheat chloroplast DNAs. I. Nucleotide divergence of genes and intergenic spacer regions located in the hot spot region. AB - The nucleotide divergence of chloroplast DNAs around the hot spot region related to length mutation in Triticum (wheat) and Aegilops was analyzed. DNA sequences (ca. 4.5 kbp) of three chloroplast genome types of wheat complex were compared with one another and with the corresponding region of other grasses. The sequences region contained rbcL and psaI, two open reading frames, and a pseudogene, rpl23' (pseudogene for ribosomal protein L23) disrupted by AT-rich intergic spacer regions. The evolution of these genes in the closely related wheat complex is characterized by nonbiased nucleotide substitutions in terms of being synonymous/nonsynonymous, having A-T pressure transitions over transversions, and frequent changes at the third codon position, in contrast with the gene evolution among more distant plant groups where biased nucleotide substitutions have frequently occurred. The sequences of these genes had diverged almost in proportion to taxonomic distance. The sequence of the pseudogene rpl23' changed approximately two times faster than that of the coding region. Sequence comparison between the pseudogene and its protein-coding counterpart revealed different degrees of nucleotide homology in wheat, rice and maize, suggesting that the transposition timing of the pseudogene differed and/or that different rates of gene conversion operated on the pseudogene in the cpDNA of the three plant groups in Gramineae. The intergenic spacer regions diverged approximately ten times faster than the genes. The divergence of wheat from barley, and that from rice are estimated based on the nucleotide similarity to be 1.5, 10 and 40 million years, respectively. PMID- 1752426 TI - The selection-mutation-drift theory of synonymous codon usage. AB - It is argued that the bias in synonymous codon usage observed in unicellular organisms is due to a balance between the forces of selection and mutation in a finite population, with greater bias in highly expressed genes reflecting stronger selection for efficiency of translation. A population genetic model is developed taking into account population size and selective differences between synonymous codons. A biochemical model is then developed to predict the magnitude of selective differences between synonymous codons in unicellular organisms in which growth rate (or possibly growth yield) can be equated with fitness. Selection can arise from differences in either the speed or the accuracy of translation. A model for the effect of speed of translation on fitness is considered in detail, a similar model for accuracy more briefly. The model is successful in predicting a difference in the degree of bias at the beginning than in the rest of the gene under some circumstances, as observed in Escherichia coli, but grossly overestimates the amount of bias expected. Possible reasons for this discrepancy are discussed. PMID- 1752427 TI - Mutation-selection balance and metabolic control theory. AB - The evolution of metabolic control is examined with models that unify approaches of classical quantitative genetics and metabolic control theory. The quantitative traits considered are the activities of enzymes embedded within metabolic pathways. In the models, polygenic mutation alters the enzyme activities (Vmax/Km) according to prescribed distributions, and the population evolves following classical haploid viability selection. Stabilizing selection operates on global properties of the metabolic pathway, including either flux or metabolite pool concentration. Analytical results and numerical simulations demonstrate several important properties of these characters, including skewed, non-Gaussian equilibrium distributions, and an expected positive correlation between activities of enzymes flanking a substrate pool undergoing stabilizing selection. The house-of-cards approximation proved to be accurate in predicting the equilibrium distribution of allelic effects for a biologically reasonable segment of the parameter space. Further experimental and theoretical work is needed before a clear assessment can be made whether the observed variance in enzyme activities is explicable by a mutation-selection balance, and this system provides an excellent opportunity for such a test. PMID- 1752428 TI - Three-locus systems impose additional constraints on pairwise disequilibria. AB - Combinations of allele frequencies and pairwise linkage disequilibrium terms, each of which is permissible at the two-locus level, may not always be permissible at the three-locus level. These additional constraints on the possible maximum and minimum values for the pairwise disequilibrium terms are formally determined and numerically analyzed. In some cases, the three-locus constraints on a pairwise disequilibrium (D) may be equivalent to the usual two locus constraints, while in others, the positive or negative range may be restricted. This can result in situations where the allowable values of D are limited to only positive or only negative values up to the extreme case where there is only a single admissible value. No additional restrictions are placed on pairwise disequilibrium values when four loci are considered, other than those imposed by the three-way combinations containing the two loci of interest. A new measure of normalized pairwise linkage disequilibrium, allowing for the three locus constraints, is defined and illustrated by an application to data from the human histocompatibility antigen (HLA) system. An analogous normalized three-way disequilibrium measure is also formulated. PMID- 1752429 TI - Selection, hitchhiking and disequilibrium analysis at three linked loci with application to HLA data. AB - The HLA system has been extensively studied from an evolutionary perspective. Although it is clear that selection has acted on the genes in the HLA complex, the nature of this selection has yet to be fully clarified. A study of constrained disequilibrium values is presented that is applicable to HLA and other less polymorphic systems with three or more linked loci, with the purpose of identifying selection events. The method uses the fact that three locus systems impose additional constraints on the range of possible disequilibrium values for any pair of loci. We have thus examined the behavior of the normalized pairwise disequilibrium measures using two locus (D'), and also three locus (D"), constraints on pairwise disequilibria in a three locus system when one of the three loci is under positive selection. The difference between these measures, delta = magnitude of D' - magnitude of D", has a distribution for the two unselected loci differing from that for the selected locus with either of the unselected loci (the hallmark is a high positive value of delta for the two unselected loci). An examination of genetic drift indicates that positive delta values are unlikely to be found in human populations in the absence of selection when recombination is greater than about 0.1%. This measure can thus provide insight into which allele of several linked loci might have been subject to selection. Application of this method to HLA haplotypes from a large French population study (Provinces Francaise) identifies selected alleles on particular haplotypes. Application of a complementary method, disequilibrium pattern analysis also confirms the action of selection on these haplotypes. PMID- 1752430 TI - Age-dependent sexually asymmetric selection: the use of intrinsic values. AB - To study the evolutionary role played by differential male and female fertility (sexual asymmetry) both between individuals and over the life span within single individuals, the terms "intrinsic male fertility" and "intrinsic female fertility" are introduced. With the help of these terms, the concept of sexual asymmetry can be made precise and its effect on the establishment and maintenance of genetic polymorphisms can be analyzed. The main conclusions are: (1) any mutant causing a modification of the male fertility parameters which result in an increased intrinsic male fertility becomes established; (2) a corollary of this is that age-specific sexual asymmetry, as results from alternating degrees of female and male flowering in successive reproduction cycles, for example, has only secondary effects on the initial growth rate; (3) under the biologically reasonable premise that modifications of life histories result from reallocation of fixed net reproduction resources (defined as constant total female and male net reproduction output), a shift of net reproduction (whether female, male, or both in arbitrary proportions) to earlier ages is evolutionarily successful in growing but not in declining populations; shifts of net reproduction to later ages have opposite consequences. PMID- 1752431 TI - Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. AB - A population of bacteria growing in a nonlimiting medium includes mutator bacteria and transient mutators defined as wild-type bacteria which, due to occasional transcription or translation errors, display a mutator phenotype. A semiquantitative theoretical analysis of the steady-state composition of an Escherichia coli population suggests that true strong genotypic mutators produce about 3 x 10(-3) of the single mutations arising in the population, while transient mutators produce at least 10% of the single mutations and more than 95% of the simultaneous double mutations. Numbers of mismatch repair proteins inherited by the offspring, proportions of lethal mutations and mortality rates are among the main parameters that influence the steady-state composition of the population. These results have implications for the experimental manipulation of mutation rates and the evolutionary fixation of frequent but nearly neutral mutations (e.g., synonymous codon substitutions). PMID- 1752432 TI - Multistage selection for genetic gain by orthogonal transformation. AB - An exact transformed culling method for any number of traits or stages of selection with explicit solution for multistage selection is described in this paper. This procedure does not need numerical integration and is suitable for obtaining either desired genetic gains for a variable proportion selected or optimum aggregate breeding value for a fixed total proportion selected. The procedure has similar properties to multistage selection index and, as such, genetic gains from use of the procedure may exceed ordinary independent culling level selection. The relative efficiencies of transformed to conventional independent culling ranged from 87% to over 300%. These results suggest that for most situations one can chose a multistage selection scheme, either conventional or transformed culling, which will have an efficiency close to that of selection index. After considering cost savings associated with multistage selection, there are many situations in which economic returns from use of independent culling, either conventional or transformed, will exceed that of selection index. PMID- 1752433 TI - p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. AB - It has been shown previously that mutant p53 can act as an immortalizing gene when cotransfected into primary rat embryo fibroblasts along with a selectable marker. To determine whether a mutation at the p53 locus is a common event in the pathways leading to spontaneous cellular immortalization, 11 clonally derived BALB/c murine embryo fibroblast lines were established by passage on a 3T3 schedule and examined for p53 alterations. By the following criteria, all 11 independently established lines contain at least one mutant allele of p53. Seven of these lines have a PAb240-reactive p53 species and exhibit an extended p53 half-life as determined by pulse-chase analysis. The p53 protein species in a subset of these lines is also capable of complex formation with the constitutive heat shock protein hsc70. p53 cytoplasmic DNAs (cDNAs) from several of these lines have been cloned by reverse transcription of cytoplasmic RNA followed by PCR amplification, and the mutations have been mapped by DNA sequence analysis. Point mutation in conserved domains of p53 appears to be a common alteration in these lines, although one established line carries a 24-bp in-frame deletion of p53. The remaining four cell lines do not express detectable p53 protein. For each line there is a different molecular event underlying the lack of p53 expression: (1) deletion of at least the first 6 exons of both p53 alleles; (2) expression of a single p53 mRNA encoding a stop codon at amino acid position 173; (3) no detectable p53 mRNA; and (4) greatly diminished expression of p53 mRNA. These findings indicate that p53 alteration commonly occurs in spontaneously immortalized BALB/c mouse embryo fibroblasts passaged on a 3T3 schedule and, therefore, may be an important event for the immortalization process. PMID- 1752434 TI - Molecular cloning of a member of a new class of low-molecular-weight GTP-binding proteins. AB - We report the cloning of a low-molecular-weight GTP-binding protein that appears to be the first member of a new class of G proteins. This G protein was cloned from the HT4 neural cell line and has the closest homology to the rab, sec4, and ypt1 members of the low-molecular-weight (LMW) G-protein family. The amino acid sequence identity is only 30% with these other LMW G proteins, but in the four conserved GTP-binding domains, amino acid identity increases to 50-100%. A unique feature that distinguishes this G protein from other LMW G proteins is its carboxy-terminal amino acid sequence -Cys-Cys-Pro. In keeping with the current nomenclature for other members of the ras superfamily, we will designate this new class as rah (ras-related homolog). On the basis of sequence homology, rah may function in vesicular trafficking and possibly in neurotransmitter secretion. PMID- 1752435 TI - A meiosis-specific protein kinase homolog required for chromosome synapsis and recombination. AB - The mek1 (meiotic kinase) mutant of Saccharomyces cerevisiae was isolated in a screen for sporulation-proficient, meiotic-lethal mutants. Diploids homozygous for a mek1 null mutation produce only 13% viable spores. mek1 spore inviability is rescued by a spo13 mutation, which causes cells to bypass the meiosis I division. In a mek1 null mutant, meiotic recombination is reduced but not completely eliminated. Nuclear spreads of meiotic chromosomes from mek1 diploids reveal numerous stretches of synaptonemal complex (SC) that are shorter than wild type SCs. Analysis of a mek1::lacZ fusion gene and Northern blot hybridization demonstrate that the MEK1 transcript is present only in meiosis. The sequence of the MEK1 gene predicts a 56.8-kD protein with homology to serine-threonine protein kinases. The MEK1 gene maps to chromosome XV, 13 cM proximal to CDC64. Models for the function of the MEK1 gene product are proposed. PMID- 1752436 TI - A new role for MCM1 in yeast: cell cycle regulation of SW15 transcription. AB - In the yeast Saccharomyces cerevisiae cell cycle-regulated SW15 transcription is essential for ensuring that mother and not daughter cells switch mating type. We have identified a 55-bp promoter sequence that appears to be responsible for restricting transcription to the late S, G2, and M phases of the cell cycle. Two proteins, MCM1, a transcription factor described previously, and SFF (SWI five factor, a newly identified factor) bind this sequence in vitro. MCM1 binds the DNA tightly on its own, but SFF will only bind as part of a ternary complex with MCM1. We observe a strong correlation between the ability of mutated SWI5 promoter sequences to form a ternary MCM1-SFF-containing complex in vitro and to activate transcription in vivo, which suggests that efficient transcription requires that both proteins bind DNA. Through its interactions with cell type specific coactivators and corepressors, MCM1 controls cell type-specific expression of pheromone and receptor genes. By analogy, we propose that SFF enables MCM1 to function as a part of a cell cycle-regulated transcription complex. PMID- 1752437 TI - RNA polymerase II carboxy-terminal domain contributes to the response to multiple acidic activators in vitro. AB - The largest subunit of RNA polymerase II contains a unique carboxy-terminal domain (CTD) that consists of repeats of the heptapeptide YSPTSPS. RNA polymerase II CTD truncation mutations affect the ability to induce transcription of a subset of yeast genes in vivo, and the lack of response to induction maps to the upstream activating sequences of these genes. Here, we report that progressive truncation of the yeast RNA polymerase II CTD causes progressive loss of trans activator-dependent transcription in nuclear extracts but has little effect on elongation or termination. Specific transcription, which is reduced by up to 50 fold in these assays, can be restored in the defective nuclear extracts by adding purified wild-type RNA polymerase II. The defects in factor-dependent transcription are observed with templates that are assembled into nucleosomes as well as with templates that are not so assembled. Defects in factor-independent transcription are also observed, but these are not as profound as those observed in the presence of trans-activators. These results indicate that the RNA polymerase II CTD functions during transcription initiation and is required for normal levels of activated transcription in vitro. PMID- 1752438 TI - Protein encoded by the exuperantia gene is concentrated at sites of bicoid mRNA accumulation in Drosophila nurse cells but not in oocytes or embryos. AB - Formation of the anteroposterior gradient of the bicoid (bcd) protein morphogen in Drosophila occurs as a consequence of the prelocalization of bcd mRNA to the anterior pole of the oocyte. bcd mRNA localization requires at least three genes, with the exuperantia (exu) gene acting earliest in the pathway. We have cloned and characterized the exu gene. Notably, we find that exu protein is colocalized with bcd mRNA during the early phase of localization, when bcd mRNA is positioned at the apical regions of the nurse cells. However, there is no colocalization at the later stage when bcd mRNA is transferred from the nurse cells to the anterior pole of the oocyte. There is no detectable exu protein in embryos. Therefore, exu acts only in initiating bcd mRNA localization and does not play a persistent role in that process. PMID- 1752439 TI - Control of Drosophila wing and haltere development by the nuclear vestigial gene product. AB - The Dipteran flight appendages, the wings and halteres, develop from larval imaginal discs that also produce other sections of the second and third thoracic adult body segments. Loss of vestigial (vg) function in Drosophila selectively eliminates wing and haltere formation. Here, we show that vg expression is spatially restricted to the presumptive wing and haltere regions of these imaginal discs. An intronic regulatory element mediates this restriction and may elaborate upon cues that activate vg expression in the embryonic disc primordia. The nuclear vg protein lacks any recognized nucleic acid-binding motif but is comprised of two putative functional domains, one of which bears similarity to part of the Deformed homeotic protein and may mediate protein-protein interactions. These results suggest that vg is directly involved in determining which thoracic imaginal disc cells will form wings and halteres, perhaps by interacting with other nuclear regulatory proteins. PMID- 1752440 TI - The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. AB - The Tat protein of human immunodeficiency virus type 1 (HIV-1) activates transcription following binding to nascent trans-activation response (TAR) RNA downstream of the transcription start site. Because Tat functions when bound to RNA, and in a position-dependent manner, it has been proposed that Tat works by a novel mechanism. Here, we perform a series of protein fusion experiments that reveal striking similarities between Tat and conventional cellular activators. Most significantly, we demonstrate that Tat can function when bound to upstream promoter DNA. This activity depends on a region within Tat that is also required for Tat to function when bound to TAR RNA. In contrast, the arginine-rich region of Tat, which is required for binding to TAR RNA, is dispensable for the function of DNA-bound Tat. When bound either to RNA or DNA Tat activity requires cooperation with promoter-bound cellular transcription factors. Finally, we show that Tat and a strong acidic activator stimulate transcription to comparable levels. On the basis of these and other results we suggest that Tat and acidic activators act on a similar step in the transcription process. PMID- 1752441 TI - Two distinct nuclear transcription factors recognize loop and bulge residues of the HIV-1 TAR RNA hairpin. AB - Transcriptional activation by the HIV-1 Tat protein requires specific residues in the hexanucleotide loop and trinucleotide bulge of the TAR RNA stem-loop structure found in the 5'-untranslated leader of all viral transcripts. Tat directly contacts residue U22 in the bulge and is thought to act in concert with cellular factors bound to the loop. We find that HeLa nuclear extracts contain two specific TAR RNA-binding proteins, designated TRP-1 and TRP-2, which compete for binding to the upper portion of the TAR hairpin. Analysis of point mutants in TAR RNA reveals that TRP-1 contacts residues in the loop that are important for trans-activation, whereas TRP-2 contacts the bulge, including the same residue (U22) that is required for the Tat-TAR interaction. Glycerol gradient sedimentation and UV cross-linking experiments indicate that TRP-1 is a large heteromeric complex containing a 185-kD RNA-binding protein, whereas TRP-2 activity derives from a family of 110- to 70-kD proteins. Interestingly, both TRP 1 and TRP-2 promote TAR-dependent transcription in vitro in the presence of Tat, although mixing experiments indicate that each of the three proteins must bind independently to TAR RNA. These findings suggest that the TAR element is recognized by two different nuclear RNA-binding proteins that affect transcriptional regulation by Tat. PMID- 1752442 TI - Efficient association of U2 snRNPs with pre-mRNA requires an essential U2 RNA structural element. AB - To understand the role of U2 RNA structure in pre-mRNA splicing we have characterized several cold-sensitive mutations in an essential stem-loop of yeast U2. Although mutant U2 is stable in vivo after a shift to restrictive temperature, splicing is rapidly inhibited, suggesting a direct effect on U2 function rather than U2 synthesis or snRNP assembly. Splicing complexes form at 23 degrees C in both mutant and wild-type extracts; however, stable association of mutant U2 snRNPs with pre-mRNA in vitro is inefficient at 15 degrees C, a temperature permissive for spliceosome assembly in wild-type extracts, indicating that the cold-sensitive defect is in U2 snRNP association with the assembling spliceosome. In vivo RNA structure probing reveals that the bulk of U2 RNA is misfolded in the mutants, even at permissive temperature. We propose that U2 stem loop IIa is recognized by an assembly factor that assists U2 snRNP binding to pre mRNA and that the cold sensitivity is due to a critical deficiency of correctly folded U2 for spliceosome assembly at low temperatures. Evolutionary conservation of the potential to form an interfering alternative RNA structure suggests the possibility that splicing could be regulated negatively at an early step by control of U2 snRNA conformation. PMID- 1752443 TI - Altered gene expression correlates with DNA structure. AB - We examined the participation of triplex DNA structure in gene regulation using a poly(dG)-poly(dC) sequence as a model. We show that a poly(dG)-poly(dC) sequence, which can adopt an intramolecular dG.dG.dC triplex under superhelical strain, strongly augments gene expression when placed 5' to a promoter. The activity of this sequence exhibits a striking length dependency: dG tracts of 27-30 bp augment the expression of a reporter gene to a level comparable to that observed with the polyoma enhancer in mouse LTK- cells, whereas tracts of 35 bp and longer have virtually no effect. A supercoiled plasmid containing a dG tract of 30 bp competes in vivo for a trans-acting factor as revealed by reduction in the reporter gene transcription driven by the (dG)29/promoter of the test plasmid, while dGs of 35 bp and longer in the competition plasmid failed to compete. In purified supercoiled plasmid DNA at a superhelical density of -0.05, dG tracts of 32 bp and longer form a triplex, whereas those of 30 bp and shorter remain double stranded under a PBS solution. These results suggest that a localized superhelical strain can exist, at least transiently, in mouse LTK- cells, and before being relaxed by topoisomerases this rapidly induces dG tracts of 35 bp and longer to adopt a triplex preventing the factor from binding. Thus, these data suggest that a poly(dG)-poly(dC) sequence can function as a negative regulator by adopting an intramolecular triple helix structure in vivo. PMID- 1752444 TI - DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1. AB - Lymphoid enhancer-binding factor 1 (LEF-1) is a pre-B and T lymphocyte-specific nuclear protein that participates in the regulation of the T-cell antigen receptor (TCR) alpha enhancer by binding to the nucleotide sequence 5'-CCTTTGAA. LEF-1 protein shares with the nonhistone high mobility group protein 1 (HMG-1) and several transcriptional regulators a single region of amino acid homology, termed the HMG box, which has been implicated in DNA binding. Here, we report the biochemical analysis of the interaction of this novel structural motif with DNA. First, amino- or carboxy-terminal truncations of the LEF-1 polypeptide delineated the HMG box as the DNA-binding domain. We purified to homogeneity a LEF-HMG domain peptide expressed in Escherichia coli and determined the equilibrium constant for specific binding to DNA as 1 x 10(-9) M. Second, cotranslation of wild-type and various truncated LEF-1 polypeptides did not generate any DNA binding heterodimers, suggesting that LEF-1 can bind DNA as a monomer. Third, methylation interference analysis indicated that the HMG domain specifically contacts DNA on one side of the double helix. Finally, changes of amino acids that are conserved among various members of the family of HMG-box proteins decreased the affinity of DNA binding by one to three orders of magnitude. Together, these data define the characteristics of specific DNA-binding by the HMG domain of LEF-1. PMID- 1752445 TI - [Pregnancy in adolescence. A review of 840 clinical cases]. AB - Pregnancy during adolescence is a medical problem and a social phenomenon of increasing importance. Opportune medical care may resolve pregnancy risk, but the lacks of this stage of life, and the lack of resources of certain communities, may frustrate the mother's desires, in such a way, that pregnancy in adolescence, will mean more a social problem than a medical one. PMID- 1752446 TI - [Sexuality and reproduction. A questionnaire at the basic secondary educational level]. AB - A 50 question survey was administered to 362 junior high school students in order to determine the level of sexual education. The objectives were to determine the themes of most interest to the students, to establish the precise participation of the school in sexual education, to define quality in teachers and to find possible differences in knowledge and attitudes according to school grade and sex. As expected, age but not sex, differed according to grades. Parents participated in the sexual education in their children in 50% of the sample; the high level of education of the majority of this group of parents will permit the development of additional programs for their participation in school related programs for sexual education. Sexual attitudes among students did not differ according to school grade. The percentage of responses about sexuality and reproduction that corresponded to materials in the curriculum was low; eighth grade students showed superior knowledge about theory, ninth grade students were superior in knowledge of more practical aspects. The principal sources of sexual education in this group were parents and teachers, 81% of the students reported having received some sexual education in the school, 51.4% as part of natural sciences course material and 12% as part of the eight grade course in social and human relations. We suggest a strategy of presenting progressively more complex materials of sexual education by grade in order to influence not only sexual attitudes but preventive sexual practices as well. PMID- 1752447 TI - [Nongynecological surgical procedures performed by an oncological gynecology service]. AB - From March, 1987 to July 1990, 1,568 surgical procedures, were done at Oncological Gynecology Service; 206 of them (13.1%) were considered as "non gynecological" surgical procedures; 182 (88.3%) were secondary to a malignity diagnosis, being the most frequent one ovarian carcinoma (54.4%). As to benign lesions, 11.7% caused "non gynecological" surgery, most frequent were severe pelvic adhesions, 41.6%, and severe endometriosis, 25%. "Non-gynecological" surgical procedure carried out most frequently was pelvic lymphadenectomy. Morbidity was 3.8%, and mortality, 0.48% due to acute myocardial infarction. The acceptance for oncologic gynecologist is justified in this series, based on survival and morbi-mortality, which permits the participation in a multidisciplinary team. PMID- 1752448 TI - [Stress urinary incontinence. Its surgical management]. AB - Ninety eight patients with stress urinary incontinence treated surgically at Central Military Hospital, were studied. We analyzed the risk factors as age, weight, height, parity, menopause age, and previous medical and surgical procedures. They were divided in two groups. The Group I, vaginal approach, with 35 patients and Group II, retropubic surgery, with 63 patients. There were no differences both groups regarding age, weight, height, parity and menopausal age. The most frequent illness associated with stress urinary incontinence, was pelvic floor relaxation. The complications were 17.1% and 33.3%, respectively. The efficacy of Burch is procedure for the management of stress urinary incontinence, with a success rate of 84.1% versus 62.1% in the vaginal approach, was confirmed. PMID- 1752449 TI - [The role of hyperpolarization and depolarization of the membrane of the human spermatozoon]. AB - The electric potential across the membrane (psi) is evaluated through the accumulation of the lipophilic, radiolabelled, triphenylmethylphosphonium (3H TPMP+), cation on membrane human sperm. The washed sperm cells, were incubated in presence of 3H-TPMP+ in low-K+ medium or high-K+ and allowed to take up the cation to steady-state (ie; 20 min at 37 degrees C). By using this differential, the value obtained was inserted in the Nernst equation, this value yielded a psi of -69 +/- 2 mV. The presence of divalent cations Zn++ and Mg++ in the incubation medium both induced a hyperpolarization of 10% and 8.6%, respectively. The addition of specific reagents such as p-chloromercuribenzene-sulfonate and ethylene-diamine-tetraacetic acid sodium salt both decreased the psi 35% and 58% respectively. The agents to act upon the components of the sperm cell membrane such as the dithiothreitol and progesterone induced hyperpolarization and depolarization of the membrane 16% and 40%, respectively. The presence of propranolol and L-alpha-lysophosphatidylcholine, which affect the ionic gradients present across the plasma membrane, both induced a depolarization from 43% and 92% respectively. Finally, the addition of tetraphenylboron (TPB-) on the incubation medium, enhanced the value of the psi 75%. These studies are transcendent because with the utilization of agents depolarizing, or hyperpolarizing we obtain changes in the psi from -80 +/- 0.6 mV, until -6 +/- 0.6 mV changes of 74 +/- 1.5 mV across of the sperm cell membrane. PMID- 1752450 TI - [Serum concentrations of estradiol and testosterone in patients with oligoasthenozoospermia and asthenozoospermia]. AB - In order to study the possible influence of circulating concentrations of estradiol (E2) and testosterone (T) on the spermatogenesis, 43 subjects, 21 to 43 years of age; 16 of them with oligoasthenozoospermia; 16 with "pure" asthenozoospermia, and 11 with normal semen study, were studied. This last group was taken as control for results evaluation and comparison. In all the cases, the presence of genitourinary infection, as well as testicular lesions and varicocele, was previously discarded. Serum concentrations of estradiol, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL), were determined by radio-analysis, in fasting blood samples. The results are shown as average values +/- standard error (mean +/- SE). Statistical analysis of differences between the groups, was done by "t" Student test in paired samples. Patients with oligoasthenozoospermia showed a significant increase (56.9%) (less than 0.001) in estradiol circulating levels, while T, FSH, LH and PRL concentrations were below normal band, and there were not significant differences between the three groups. These results suggest that the excess of estradiol or of some of its metabolites could affect normal production of spermatozoa, maybe due to a direct effect on germinal epithelium of testicle. PMID- 1752451 TI - Neurochemistry of hepatic encephalopathy. PMID- 1752452 TI - Systematic comparison of conventional oesophageal manometry with oesophageal motility while eating bread. AB - Conventional oesophageal manometry is seldom accompanied by symptoms and may indeed be normal in patients with a history of dysphagia. We have recently shown that oesophageal manometry during eating may be helpful in the evaluation of patients with dysphagia but there has been little systematic comparison of fed oesophageal motor patterns with conventional clinical manometry. Oesophageal manometry in response to water swallows and during eating was therefore examined in 58 consecutive patients who had been referred for clinical oesophageal function studies. The patients were divided into three groups according to the percentage of peristaltic activity during conventional manometry: group 1 (n = 21) had 100% peristalsis; group 2 (n = 29) had 1-99% peristalsis and group 3 (n = 8) were aperistaltic. All the patients in group 3 had achalasia and remained aperistaltic during eating, however, was less than with water swallows in both group 1 (53% compared with 100%) and group 2 (49% compared with 82.3%) patients. Synchronous contractions and non-conducted swallows were correspondingly increased during eating. Although there was a significant correlation between the amplitude of peristaltic contractions with water and bread in groups 1 and 2, mean peristaltic amplitudes were less with bread than with water swallows. The data show that there are substantial differences in the distal oesophageal motility patterns produced by water swallows and by eating. Conventional manometry with water swallows does not allow prediction of the fed oesophageal motility pattern, except in patients with achalasia. PMID- 1752453 TI - Ambulatory 23 hour recording of intraoesophageal pressures in normal volunteers: a propagation analysis from one proximal and two distal recording sites. AB - pH data were obtained from one level and pressure data from three levels in the oesophagus over 23 hours in 24 healthy volunteers, followed by automatic propagation analysis of motility data and analysis of time with pH less than 4. Apart from periods of meal ingestion, isolated pressure complexes were found more frequently in the distal than in the proximal oesophagus. This was especially common in the recumbent position at night. Most contractions of the proximal oesophagus were propagating. In the distal oesophagus were propagating. In the distal oesophagus propagating pressure waves were more frequent during the day than during the night and most frequent during meals. The state of consciousness rather than body position per se is important in determining the frequency of simultaneous contractions in the distal oesophagus. PMID- 1752454 TI - Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis. AB - Nocturnal gastro-oesophageal reflux may be important in the pathogenesis of reflux oesophagitis. This study aimed to determine whether: (1) gastro oesophageal reflux occurs during sleep in patients with reflux oesophagitis and, if so, to explore the mechanism, and (2) the sleep pattern of patients with oesophagitis is different from that of control subjects. After a standard evening meal, simultaneous manometric, oesophageal pH, and polysomnographic recordings were obtained in 11 patients with endoscopic oesophagitis and 11 control subjects. Patients with gastrooesophageal reflux disease had significantly more total reflux episodes throughout the nocturnal monitoring period than control subjects (105 v 6). Ninety two of 105 episodes of gastro-oesophageal reflux in patients occurred during the awake state and 10 during sleep stage II. A number of reflux episodes occurred during brief periods of arousal from the various sleep stages. Of the 105 reflux events recorded in patients, 42 were induced by transient lower oesophageal sphincter relaxation, 20 by stress reflux, 22 by free reflux mechanisms, and in 21 the mechanism was unclear. The sleep pattern and the time spent in each sleep stage was not different between the two groups. It is concluded that the awake state is crucial for the occurrence of nocturnal reflux episodes in normal subjects as well as in patients with reflux oesophagitis and that the difference between the frequency of gastro-oesophageal reflux between normal subjects and patients cannot be explained by different sleep patterns. PMID- 1752455 TI - Healing and prevention of relapse of reflux oesophagitis by cisapride. AB - Altogether, 138 patients were included in a study aimed at evaluating the effect of cisapride on healing and relapse of oesophagitis shown endoscopically. In the first phase of the study cisapride was given in an open fashion at 10 mg four times a day for 8 to 16 weeks, and healing was obtained in 69% of patients. Healing occurred later in patients with grades II to IV oesophagitis. The total score for reflux symptoms decreased by 67%. Eighty of the healed patients were included in the second phase. They were randomly assigned to double blind treatment with either cisapride 10 mg (n = 37) or placebo (n = 43) twice a day. Control endoscopy was performed when symptoms recurred or at the end of the six month trial. The cumulative percentage of patients in remission was higher (p = 0.06, survival analysis) in the cisapride group than in the placebo group, the relapse rates being 20% and 39%. The duration of remission tended to be longer in patients with a lower initial degree of oesophagitis. Adverse effects were no more frequent with cisapride than with placebo. In conclusion, cisapride is efficacious in healing oesophagitis, and, unlike other gastrointestinal prokinetic drugs or low dose cimetidine (400-800 mg daily) or ranitidine (150 mg daily), it may prevent relapse of oesophagitis. PMID- 1752456 TI - Is Helicobacter pylori associated hypergastrinaemia due to the bacterium's urease activity or the antral gastritis? AB - Eradication of Helicobacter pylori is associated with a fall in serum gastrin but the way in which the infection raises the serum gastrin concentration is not clear. It may be related to the ammonia produced by the bacterium's urease stimulating gastrin release by the antral G cells. Alternatively, the antral gastritis induced by the infection may modify the regulation of gastrin release. We have examined serum gastrin in 10 patients before and 24 hours after starting triple anti-H pylori treatment consisting of tripotassium dicitrato bismuthate 120 mg four times daily, metronidazole 400 mg three times daily, and amoxycillin 500 mg three times daily. The urease activity, assessed by the 20 minute value of the 14C-urea breath test, fell from a median of 176 (range 116-504) kg% dose/mmol CO2 x 100 pretreatment to 5 (2-15) at 24 hours (p less than 0.005). The median antral gastritis score was 6 (4-6) pretreatment and fell to 3 (2-5) at 24 hours (p less than 0.02), and this was due to resolution of the polymorphonuclear component. Despite this complete suppression of bacterial urease activity and partial resolution of antral gastritis the median basal gastrin concentration remained unchanged, being 57 ng/l (45-77) pretreatment and 59 ng/l (45-80) at 24 hours and the median integrated gastrin response to a standardised meal was also unaltered, being 4265 ng/l/min (range 1975-8350) and 4272 ng/l/min (range 2075 6495) respectively. These findings do not support a causal association between H pylori urease activity and hypergastrinaemia and show rapid improvement of antral gastritis after starting anti-H pylori treatment. PMID- 1752457 TI - Long term serological surveillance after treatment of Helicobacter pylori infection. AB - Fifteen patients with type B gastritis caused by Helicobacter pylori infection were treated with 'triple' therapy consisting of colloidal bismuth subcitrate, amoxycillin, and metronidazole. All were followed up as outpatients every three months for at least one year. After 'triple' therapy a significant (p less than 0.01) and persistent reduction in IgA and IgG antibody levels against H pylori was detected. In three patients recurrent active infection with H pylori at nine and 12 months was detected by a rise in IgA (three patients) and IgG (two patients) antibody levels against H pylori and worsening of symptoms, and was confirmed by culture and histology. In 11 patients, the absence of infection at 12 months was confirmed by culture and histology. In a control group of 13 patients with type B gastritis who received no antibacterial treatment, specific IgA and IgG antibody levels against H pylori remained unchanged during 12 months of follow up. Although specific IgG against H pylori is the most widely used serological test for screening, our data indicate that specific IgA is also valuable in monitoring treatment. These serological tests are easy to perform, relatively inexpensive, devoid of radioactivity and are very acceptable to patients. It is concluded that serological testing is the preferred method for follow up after treatment for H pylori infection and will probably replace endoscopy or the urea breath test. PMID- 1752458 TI - Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine. AB - The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach. PMID- 1752459 TI - Importance of the stomach in maintaining calcium homoeostasis in the rat. AB - The stomach helps to maintain calcium homoeostasis by making dietary calcium accessible for uptake in the intestines, although the effect of the stomach on calcium homoeostasis is poorly understood. We examined the effect on blood calcium of gastric surgery in the rat. Within three weeks gastrectomy and fundectomy (excision of the acid producing part of the stomach) induced a slight lowering of the blood calcium concentration. When parathyroidectomy was combined with either gastrectomy or fundectomy the blood calcium concentrations promptly dropped to values lower than after parathyroidectomy alone. The mortality was close to 100% during the first three weeks after combined parathyroidectomy and gastric surgery. It was nil in rats subjected to parathyroidectomy alone. Gastrectomised rats absorbed Ca2+ better than unoperated control rats, possibly reflecting the fact that the serum 1,25-dihydroxyvitamin D concentration was raised. Gastrectomised rats had a food intake that was about 70% of that in intact rats, and the amount of dietary calcium absorbed (net absorption per kg body weight) by the gastrectomised rats was approximately 65% of that in intact control rats. We conclude that the acid producing part of the stomach is important for calcium homoeostasis, since its removal induced lethal hypocalcaemia in parathyroidectomised rats. One possible explanation for the hypocalcaemia induced by gastrectomy is a progressive calcium deficit. In addition, the loss of calciotrophic hormones originating in the stomach may contribute. PMID- 1752460 TI - Osteopenia and osteomalacia after gastrectomy: interrelations between biochemical markers of bone remodelling, vitamin D metabolites, and bone histomorphometry. AB - The prevalence of metabolic disease in a population of 68 postgastrectomy patients was assessed using histomorphometric evaluation of transiliac bone biopsy specimens after tetracycline double labelling. Trabecular bone volume was significantly lower in the postgastrectomy group (p less than 0.01): 62% of the patients had increased osteoid surface, 56% increased osteoid thickness, and 24% increased mineralisation lag time. Only 18%, however, fulfilled the diagnostic criteria for osteomalacia--increased osteoid thickness and increased mineralisation lag time. Postgastrectomy patients had reduced serum concentrations of calcium (p less than 0.01), phosphate (p less than 0.01), and 25-hydroxyvitamin D, while levels of alkaline phosphatase and 1,25 dihydroxyvitamin D were high (p less than 0.01). The severity of the mineralisation defect as reflected by mineralisation lag time was positively correlated to serum 25-hydroxyvitamin D, but unrelated to serum 1,25 dihydroxyvitamin D. Multiple linear regression analysis showed that serum 25 hydroxyvitamin D, age, and the duration of postoperative follow up were significant determinants of the mineralisation defect in a given patient. The limited value of serum markers in the diagnosis of osteomalacia was emphasised by the fact that six of the eight patients with osteomalacia had normal serum levels of calcium and alkaline phosphatase, and five of the eight had values for 25 hydroxyvitamin D in the normal range for healthy control subjects. The results clearly show the need for vitamin D supplementation and regular control after gastric resection. PMID- 1752461 TI - Calmodulin independence of human duodenal adenylate cyclase. AB - The calmodulin and calcium dependence of human adenylate cyclase from the second part of the duodenum was assessed in washed particulate preparations of biopsy specimens by investigating (a) the concentration dependent effects of free [Ca2+] on enzyme activity, (b) the effects of exogenous calmodulin on enzyme activity in ethylene glycol bis (b-aminoethyl ether)N,N'-tetra-acetic acid (EGTA) washed particulate preparations, and (c) the effects of calmodulin antagonists on enzyme activity. Both basal (IC50 = 193.75 (57.5) nmol/l (mean (SEM)) and NaF stimulated (IC50 = 188.0 (44.0) nmol/l) adenylate cyclase activity was strongly inhibited by free [Ca2+] greater than 90 nmol/l. Free [Ca2+] less than 90 nmol/l had no effect on adenylate cyclase activity. NaF stimulated adenylate cyclase activity was inhibited by 50% at 2.5 mmol/l EGTA. This inhibition could not be reversed by free Ca2+. The addition of exogenous calmodulin to EGTA (5 mmol/l) washed particulate preparations failed to stimulate adenylate cyclase activity. Trifluoperazine and N-(8-aminohexyl)-5-IODO-1-naphthalene-sulphonamide (IODO 8) did not significantly inhibit basal and NaF stimulated adenylate cyclase activity when measured at concentrations of up to 100 mumol/l. These results suggest that human duodenal adenylate cyclase activity is calmodulin independent but is affected by changes in free [Ca2+]. PMID- 1752462 TI - Search for the ideal oral rehydration solution: studies in a model of secretory diarrhoea. AB - In situ perfusion of whole rat small intestine was used to compare the efficacy of five oral rehydration solutions in promoting water and sodium absorption in normal intestine and secreting intestine after exposure to cholera toxin. Solutions varied in their sodium (35-90 mmol/l) and glucose (111-200 mmol/l) concentrations, molar ratio of glucose:sodium (1.2-5.8), and osmolality (281-331 mOsmol/kg), and contained either bicarbonate (18-30 mmol/l) or citrate (10 mmol/l). In normal intestine all solutions promoted net water absorption. Cholera toxin induced reproducible water secretion but all solutions reversed this to absorption. Water absorption was greatest with solutions containing sodium 60 mmol/l and glucose 111 or 140 mmol/l, and with a glucose:sodium ratio approximately 2, in both normal and secreting intestine. All solutions promoted net glucose absorption in both normal and secreting intestine. Net sodium absorption occurred with solutions containing greater than or equal to 60 mmol/l sodium in normal intestine but sodium secretion occurred from all solutions in secreting intestine. Sodium movement was directly related to the sodium concentration of the solution and sodium secretion occurred despite net water and glucose absorption. We consider that these studies may guide future development of oral rehydration solutions. PMID- 1752463 TI - Small intestinal length: a factor essential for gut adaptation. AB - Changes in small intestinal structure, cytokinetics, and function are dynamic ways in which the gut adapts to diet, disease, and damage. Adequate length provides a static 'reserve' permitting an immediate response to pathophysiological changes. The length of the small intestine from conception to adulthood using data taken from eight published reports of necropsy measurement of 1010 guts is described. Mean length at 20 weeks' gestation was 125 cm, at 30 weeks' 200 cm, at term 275 cm, at 1 year 380 cm, at 5 years 450 cm, at 10 years 500 cm, and at 20 years 575 cm. Prenatal small intestinal growth exceeded that of body length according to the law: small intestinal length alpha body length to the power 4/3. After birth there was a noticeable deceleration: small intestinal length alpha body length to the power 1/2. The coefficient of variation of small intestinal length postnatally was 24%, sixfold greater than for body length. The rapid prenatal small intestinal growth rate ensures that the mature newborn has adequate small intestine to meet postnatal nutritional demands, but handicaps the preterm infant who undergoes intestinal resection. The wide variation in lengths suggests a 'surplus' surface area that is immediately available to respond, independent of dynamic mucosal changes, to fluctuations in food availability, local intestinal disease, damage, rapid transit, and resection. PMID- 1752464 TI - Value of in vivo electrophysiological measurements to evaluate canine small bowel autotransplants. AB - This study aimed to develop a non-invasive method for in vivo measurement of the transepithelial potential difference in the canine small bowel and to evaluate this parameter in small bowel autotransplants. In group 0 (control group, n = 4), two intestinal loops were created without disturbing their vascular, neural, and lymphatic supplies. In group I (successful autotransplants, n = 11), two heterotopic small bowel loops were constructed. Long term functional sequelae of vascular, neural, and lymphatic division were studied. Group II (n = 6) consisted of dogs with unsuccessful autotransplants suffering thrombosis of the vascular anastomosis, which resulted in ischaemic small bowel autografts. In group I, values of spontaneous transepithelial potential difference, an index of base line active electrolyte transport, were significantly lower compared with group 0 (p less than 0.05), probably as a result of denervation of the autotransplants. Both theophylline and glucose stimulated potential difference responses, measuring cyclic adenosine monophosphate mediated chloride secretion and sodium coupled glucose absorption respectively, showed negative luminal values in group I at all time points after transplantation. These transepithelial potential difference responses diminished progressively with time. From day 21 onwards both theophylline and glucose stimulated potential difference responses were significantly less than the corresponding responses at day seven (p less than 0.05). Morphometric analysis showed that the reduction of transepithelial potential difference responses preceded degenerative mucosal changes in the heterotopic small bowel autografts. In group II, potential difference responses to theophylline and glucose showed positive luminal values (p<0.01 v group I), probably as a result of passive potassium effusion from necrotic enterocytes. PMID- 1752465 TI - Body composition and calcium metabolism in adult treated coeliac disease. AB - Twenty two treated adult patients with coeliac disease (aged 20-70 years) were examined. Body composition was assessed from anthropometry and directly measured by dual photon absorptiometry. Bone mineral content was measured in the spine (dual photon absorptiometry) and at two forearm sites (single photon absorptiometry). Compared with age matched healthy subjects, treated coeliac patients had lower body mass index (-5%, p less than 0.05) and lower directly measured total body fat mass (-30%, p less than 0.001). They also had decreased bone mineral content (-9 to -13%, p less than 0.01) in the spine and in the forearms. The serum concentrations of albumin, D vitamin binding protein, and iron were reduced (-6 to -22%, p less than 0.01), but otherwise blood and urine analyses were normal. We conclude that this group of treated adult coeliac patients had a reduced fat mass and bone mineral content compared with the general population. PMID- 1752466 TI - Faecal bile acid excretion in children with inflammatory bowel disease. AB - Faecal bile acid excretion and intestinal transit time were studied in 18 children with inflammatory bowel disease in clinical remission and with normal stools: 16 with ulcerative colitis, two with Crohn's colitis, mean age 14 years (range 10-17 years). Five healthy children, mean age 12.4 years (range 10-17 years), were studied as control subjects. Most patients were taking sulphasalazine, but none were taking steroids. Transit time was determined by carmine and did not differ between groups. Faeces were collected for 72 hours, and faecal water was prepared by centrifugation of faeces at 15,000 x g for two hours. Bile acids in total faeces and faecal water were studied using capillary gas-liquid chromatography-mass spectrometry. Faecal excretion of total bile acids, unconjugated bile acids, and glycine and taurine conjugates were significantly increased in patients as was faecal water excretion of total bile acids, particularly the taurine conjugates and cholic and chenodeoxycholic acids. Total concentrations of bile acids in faeces and faecal water were two to five times higher in patients. The children with inflammatory bowel disease in clinical remission had high excretion and concentration rates of bile acids, especially taurine conjugates, in both total faeces and faecal water, a finding of considerable interest in the pathogenesis of malignancy in these diseases. PMID- 1752467 TI - Postprandial hypergastrinaemia in patients with colorectal cancer. AB - Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis. PMID- 1752468 TI - Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs. AB - The effects of loperamide (0.1 mg/kg orally) on net colonic water absorption, orocolonic transit time, and intestinal motility were investigated in pigs chronically fitted either with two cannulas in the proximal colon and a catheter in the duodenum and the ileum or with intraparietal electrodes on the duodenum, jejunum, caecum, and proximal colon and a duodenal catheter. Loperamide, given 20 minutes before a meal reduced significantly colonic net water absorption for 10 hours after eating. It also reduced colonic flow rate, increased orocolonic transit time, modified the postprandial intestinal motility by inducing supplementary phase 3 motor complexes and did not affect caecocolonic motility. Intraduodenal infusion of a hypertonic solution of mannitol (900 mOsm/l; 0.6 ml/minute) for the first postprandial hour strongly reduced or reversed net colonic water absorption, increased the colonic flow rate, accelerated the orocolonic transit, and induced profuse diarrhoea. After loperamide administration, all these effects were blocked and the relative colonic water absorption, expressed as the fraction of flow entering the colon, was strongly increased. Mannitol did not modify motility of the small and large intestine, and supplementary phase 3 motor complexes were observed when mannitol infusion was preceded by loperamide administration. It is concluded that in experimental osmotic diarrhoea loperamide causes a reduction in digesta flow entering into the colon, mediated by its action on small intestinal motility, and an increase in colonic water absorption. PMID- 1752469 TI - Intermittent rectal motor activity: a rectal motor complex? AB - Prolonged nocturnal recordings from multiple sites in the anorectum and duodenum were performed in 12 healthy volunteers to investigate the presence and determine the characteristics of nocturnal rectal motor activity and assess any synchronicity with phase III of the small intestinal migrating motor complex. Runs of phasic contractions of two contractile frequencies (3 or 6/minute), sustained for more than three minutes, and preceded and followed by motor quiescence were observed in 10 of the 12 subjects. This phenomenon is similar to that described by other investigators and termed the 'rectal motor complex'. The runs of contractions showed considerable inter- and intrasubject variation, with a duration of 3-30 minutes (median 9.0), amplitude of 10-55 mm Hg (median 20.0), and periods of 10-420 minutes (median 55.5) between contractile activity. There was no propagation through the rectum, the phasic motor activity rarely occurred simultaneously at more than one rectal recording site. No consistent relation with phase III of the small intestinal migrating motor complex was observed in any subject. In view of these findings, we question whether this intermittent motor activity merits the term 'rectal motor complex'. PMID- 1752470 TI - Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods. AB - Six jaundiced patients with primary sclerosing cholangitis and a dominant biliary stricture were managed by endoscopic placement of endoprostheses. Five showed considerable improvement within weeks of stenting: their serum bilirubin concentration fell from mean (range) 266 mumol/l (63-681) to 65 mumol/l (10-280) after one month. One patient required a liver transplant at five months because of continued deterioration in hepatic function. Follow up of 12-49 months in the remaining five patients shows sustained biochemical improvement, with repeat cholangiograms indicating doubling of the minimum calibre of the extrahepatic bile duct in four patients and considerable shortening of stricture length in three. Three patients developed sepsis at the time of the initial endoprosthesis insertion: surgical drainage was necessary in one. Endoscopic methods of improving biliary-enteric drainage in jaundiced patients with primary sclerosing cholangitis may be preferable to surgical and percutaneous methods, which may complicate subsequent liver transplantation. PMID- 1752472 TI - 'Solitary' necrotic nodules of the liver: an aetiology reaffirmed. AB - Morphological features of lesions conforming to the description of solitary necrotic nodules of the liver were compared with liver haemangiomata and necrotic tumour metastases in the liver. An origin in haemangiomata is confirmed for most of the lesions studied, although the necrotic nodule may represent the end stage of a variety of lesions. These lesions are usually benign, although necrotic nodules are often mistaken for liver metastases. A reticulin stain is useful in assessing the lesions. PMID- 1752471 TI - Effect of dietary calcium on the colonic luminal environment. AB - Dietary supplementation with calcium may prevent the development of colorectal cancer. This mechanism may be related to fatty acid and bile salt chelation in the small bowel forming non-toxic calcium-soap compounds. Calcium may also act locally or systemically on the colonic mucosa. Faecal concentrations of free fatty acids and free bile acids were measured in 17 Sprague-Dawley rats (weighing 472 (39 g)) whose daily calcium intake had been trebled by enriching the chow and adding calcium lactate (24 g/l) to the drinking water. Mean (SEM) faecal concentrations of free bile acids were 33% less than in 19 controls (1.23 (0.15) v 1.82 (0.20) mg/g; p less than 0.001), whereas free fatty acid concentrations were 117% higher (14.68 (3.59) v 6.76 (2.41) mg/g; p less than 0.02). The 'direct' effect of calcium was assessed by organ culture of rat colonic explants in three different concentrations of calcium. Crypt cell production rate (measured by a stathmokinetic technique), which was (mean (SEM)) 4.80 (0.23) cells/crypt/h in control medium (Ca2+ = 2.14 mmol/l), fell by 43% when calcium concentration was doubled (p less than 0.05) and by a further 43% when the concentration was trebled (p less than 0.02). Calcium binds free fatty acids but not free bile acids intraluminally. Calcium has a direct antitropic action on colonic crypts. PMID- 1752473 TI - Diclofenac hepatitis. AB - The characteristics of liver damage associated with the use of diclofenac, a popular nonsteroidal anti-inflammatory drug, were investigated by reviewing adverse drug reaction reports for Australia. Twenty six patients were reported for whom diclofenac was the sole suspected drug cause of their liver damage. The average age of the patients was 64 years (range 37-84 years); 19 (70%) were women. The most common clinical features were jaundice, hepatomegaly, anorexia, and nausea. Features of drug hypersensitivity were not reported. Duration of treatment with diclofenac before the onset of the illness ranged from 6-417 days (median 76 days). The most prominent biochemical abnormalities were raised serum aspartate transaminase and alanine transaminase activity of up to 30 to 40 times the upper limit of the normal range. Recovery generally started soon after withdrawal of diclofenac and the decrease in aspartate transaminase and alanine transaminase for the group was exponential, with half lives of around 13 days. The average total dose taken by 18 patients for whom accurate data were available was 8.7 g (range 1.4-63.5 g) and, unexpectedly, there was a significant relation between the logarithm of the dose of diclofenac and the logarithms of the peak and mean transaminase levels. Hepatocellular damage during treatment with diclofenac seems to be a rare event. From this analysis of Australian reports it seems that in a small subgroup of patients liver injury may be a direct toxic effect of diclofenac or a metabolite. PMID- 1752474 TI - Morphological and immunohistochemical analysis of the human liver in chronic pancreatitis. AB - Morphological and immunohistological appearances of liver biopsy specimens are described in a personal series of 52 patients undergoing operation for chronic pancreatitis. The findings are compared with those in a series of 10 histologically normal liver biopsy specimens from patients without pancreatitis. Alcohol was the prime aetiological agent in 40 of the 52 patients (77%). No obvious damage to hepatic parenchymal cells or biliary structures was observed but minor morphological changes of alcohol associated liver disease were seen in 42% of specimens. The most consistent finding, present in 48 specimens (92%), was a chronic inflammatory cell infiltration of portal tracts. In all but one case, T lymphocytes predominated, but a few B cells were present. In four biopsy specimens, T cells spilled over into adjacent hepatic parenchyma, but there was no evidence of T cell mediated cytotoxic damage to the parenchymal cells or biliary epithelium. It is suggested that these inflammatory cells are in transit from the pancreas through the liver via the portal circulation and may reflect the underlying pathogenesis of chronic pancreatitis rather than alcoholic liver disease. PMID- 1752475 TI - Is tobacco a risk factor for chronic pancreatitis and alcoholic cirrhosis? AB - In a case control study alcohol intake and tobacco use were assessed between 1975 and 1987 in 103 male patients suffering from alcoholic cirrhosis of the liver, in 145 patients with chronic pancreatitis, and in 264 control subjects. The patients with chronic pancreatitis were significantly younger than the patients with cirrhosis (mean (SD) age 41.92 (2.4) v 60.9 (11.6) years). Among the patients with chronic pancreatitis, 94% were both smokers and drinkers compared with 83% of patients with cirrhosis of the liver. The relative risks for each disease were calculated by conditional multiple logistic regression. Whereas daily intake of alcohol was a major risk factor for both cirrhosis of the liver and chronic pancreatitis, smoking was significantly related only to the risk of having chronic pancreatitis. Moreover, the mean age at onset of pancreatitis was lower among smokers. PMID- 1752476 TI - Gastric output of pancreatic secretory trypsin inhibitor is increased by misoprostol. AB - Pancreatic secretory trypsin inhibitor (PSTI) is a potent protease inhibitor that also has growth promoting activity. It has recently been identified in the foveolar cells of the stomach, which secrete mucus. We examined the effects of the prostaglandin E1 analogue misoprostol on gastric PSTI output. Seven normal volunteers took part. An initial period of gastric aspiration was followed by four 40 minute periods of gastric perfusion at 5 ml/minute of: 0.14 mol/l saline, 0.17 mmol/l bicarbonate, bicarbonate with misoprostol 400 micrograms, and then bicarbonate again. All perfusates contained polyethylene glycol 4000 as a marker. Misoprostol increased median gastric secretion of PSTI from 11 to 33 micrograms/hour (p less than 0.05), producing concentrations in gastric juice six times higher than those found in jejunal juice and about 1/30 of the values seen in pancreatic juice. Median mucus secretion increased to a lesser extent from 29 to 38 mg/hour during misoprostol. There was no change in intragastric concentrations of protein or of epidermal growth factor during infusion of misoprostol. Infusion of pentagastrin (6 micrograms/kg/hour) had no effect on gastric secretion of mucus, PSTI, or protein. Human gastric mucus was degraded on incubation with trypsin in vitro and this was prevented by the addition of PSTI. These results suggest that gastric PSTI may protect the gastric mucus layer against refluxed pancreatic proteases. Increased output of PSTI during microprostol may contribute to the protective effect of this drug. PMID- 1752477 TI - National statistics for diet, alcohol consumption, and chronic pancreatitis in England and Wales, 1960-88. AB - This study compared national statistics for consumption of alcohol and dietary intake with the numbers of cases of chronic pancreatitis as recorded in a 10% sample of all hospital discharges (Hospital In-Patient Enquiry) and with the annual number of deaths. Hospital discharges for chronic pancreatitis became more common throughout the study period (7.0-11.1 discharges per million per year in 1960-4; 26.8-32.4 discharges per million per year in 1980-4). The most rapid increase was from 1975-82. The rate increased fourfold in men, but only twofold in women, and the increase began earlier in men (1976) than in women (1980). Annual deaths from chronic pancreatitis also rose progressively (46-70 in 1960-4; 64-91 in 1985-8). The annual per capita consumption of alcohol rose from 4.0-4.9 litres in 1960-4 to a peak of 7.7 litres in 1979; it has been relatively stable (6.9-7.6 litres) in 1980-8. Total dietary energy intake assessed in the National Food Survey fell progressively, with a correspondingly greater fall in carbohydrate intake, so that the energy contributions of fat and protein rose slightly, although total fat and protein consumption fell from 1965-9 to 1980-4. These changes were small in relation to total dietary intake and seemed to be unrelated to the changes in the numbers of chronic pancreatitis discharges. There was a close correlation (r = 0.96) between per capita alcohol consumption and the numbers of discharges with chronic pancreatitis six years later. This suggests that epidemiological trends in chronic pancreatitis in the United Kingdom might be predictable from population based statistics of alcohol consumption. PMID- 1752478 TI - Gall bladder emptying patterns in response to a normal meal in healthy subjects and patients with gall stones: ultrasound study. AB - In this study gall bladder emptying patterns in response to a solid meal were studied using ultrasound. A similar triphasic pattern was seen in eight healthy control subjects and eight patients with gall stones, with 'early' and 'late' net emptying phases separated by a period of net refilling with peak postprandial gall bladder volumes occurring at (mean (SD)) 33.1 (17.9) minutes and 27.4 (18.8) minutes in control subjects and patients, respectively. A phase of slower net emptying followed, which was complete at 146 (33) minutes in control subjects and 125 (33) minutes in the gall stone patients (not significant). Superimposed upon this overall triphasic pattern, postprandial gall bladder emptying was punctuated by repeated short lived episodes of filling and emptying. The mean (SD) estimated postprandial bile outputs were 0.83 (0.34) ml/min in four control subjects and 1.2 (1.1) ml/min in seven patients with gall stones. We propose a 'washout' model to reconcile this large turnover of bile with the concentrating and storage functions of the gall bladder and predict that the extent rather than the rate of gall bladder emptying is important in determining stasis of bile in the gall bladder. PMID- 1752479 TI - Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations. AB - The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon 14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration. PMID- 1752480 TI - Response to autoimmune enteropathy to cyclosporin A therapy. AB - Small bowel enteropathies that are associated with an autoimmune process are often resistant to treatment. Two children with autoimmune enteropathy were treated with cyclosporin A for eight months. Both improved, as assessed by growth, small intestinal mucosal morphology, and carbohydrate absorption. Cyclosporin A is useful in the treatment of autoimmune enteropathy. This report also suggests that T cell activation (which is suppressed by cyclosporin A) is important in the pathogenesis of this condition. PMID- 1752481 TI - Angiodysplasia and ileal carcinoid. AB - A case of angiodysplasia, symptomatic for 18 years, is presented. This case highlights the difficulty of establishing a diagnosis. Associated findings included aortic stenosis and a carcinoid tumour of the ileum. Despite transfusion of a total of 1200 units of blood the liver was normal at necropsy. PMID- 1752482 TI - Postprandial mesenteric blood flow. PMID- 1752483 TI - Helicobacter pylori infection in healthy people. PMID- 1752484 TI - Medical treatment of bleeding peptic ulcer: old drugs, new regimens. PMID- 1752485 TI - Advances in the management of early stage ovarian cancer. PMID- 1752486 TI - Surgery without adjuvant chemotherapy for early epithelial ovarian carcinoma after comprehensive surgical staging. AB - From January 1981 to December 1987, 82 patients with carcinoma of the ovary, Stages 1A, 1B, and 1C (cytology negative) (FIGO 1988), were enrolled in this study following accurate surgical staging. No patient received adjunctive therapy and all were followed from 2 to 6 years with a mean duration of follow-up of 4 years. Sixty-eight patients were eligible for review--thirty-nine Stage 1A, six Stage 1B, and twenty-three Stage 1C (twenty-one with tumor rupture, two with excrescences). The mean age was 48.8 years. Three patients had a recurrence of their disease (one death). Forty patients in this series were Stage 1A or 1B (well or moderately well differentiated, no excrescences, no rupture). Only 1 patient in this group (with clear cell carcinoma) has recurred, suggesting that this patient population can be followed without adjunctive therapy. Adhesions or rupture in this series did not affect outcome. Clear cell tumors may have an ominous prognosis despite apparent local disease. PMID- 1752487 TI - Stage I ovarian epithelial carcinoma: survival analysis following definitive treatment. AB - Between 1977 and 1986, 55 patients with surgical stage I ovarian epithelial carcinoma were managed in a definitive fashion, which included surgical staging and adjuvant therapy in 51 of 55 patients (93%) and second-look laparotomy. The mean follow-up time from the data of reassessment surgery was 94 months, allowing sufficient time to facilitate the identification of one or more subgroups of patients at risk of having persistent disease or developing a recurrence. Treatment failures were detected at second-look laparotomy in 6 patients (11%), and an additional 5 patients (9%) subsequently had recurrences after being declared free of disease at second-look reassessment. Analysis of pathologic variables identified grade and substage as important prognostic factors, with 8 of the 9 deaths (89%) being associated with Broders grade 3 or 4 and/or stage IC. Within the bivariate model consisting of patients harboring poorly differentiated (grade 3 or 4) stage IC lesions, 6 of 14 patients (43%) are dead from disease, yielding a long-term survival rate that at best approximates the survival rate associated with optimally reduced (microscopic residual) stage III patients subjected to contemporary adjuvant therapy and reassessment surgery. These data suggest that intensive therapy as utilized in advanced disease, including platinum-based chemotherapy, second-look laparotomy, and innovative salvage or investigational consolidation therapy, is equally applicable to this "high-risk" stage I group. PMID- 1752488 TI - A phase II trial of adjuvant cisplatin and doxorubicin in stage I epithelial ovarian cancer. AB - We have treated 26 patients with Stage I ovarian cancer with platinum-based chemotherapy. Patients received 50 mg/m2 cisplatin and 50 mg/m2 doxorubicin every 21 days for six cycles. Eighteen patients had complete surgical staging defined as total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and aortic node sampling, omentectomy, and cytology. Eight patients had all of the above with the exception of node sampling. The overall median follow-up for the group is 43+ months. Three patients had grade 1 tumors with positive washings or capsule invasion and are disease free with a median follow-up of 53+ months. Of 23 patients with grade 2-3 tumors, 22 are alive and free of disease with a median follow-up of 42+ months. There has been 1 recurrence, at 18 months, in a patient who had complete staging and a grade 2 tumor. The patient recurred with carcinomatosis, documented by laparoscopy. There was no significant hematologic, neurologic, or renal toxicity encountered in any patient. Adjuvant combination chemotherapy is beneficial for selected patients with early-stage ovarian cancer who are at high risk for failure after surgical treatment alone. PMID- 1752489 TI - Stage I endometrial carcinoma: treatment of nonoperable patients with intracavitary radiation therapy alone. AB - From 1976 to 1981, 171 patients with stage I endometrial adenocarcinoma (FIGO, 1971) underwent intracavitary radiotherapy alone because of medical contraindications to surgery and external-beam irradiation. The mean age of patients was 71 years, with the majority of patients being in the age group of 70 79 years. The intracavitary therapy consisted of intrauterine insertions of radium implants in three consecutive courses according to the packing method of Heyman. The estimated dose delivered to point A and to point B was 80 and 20 Gy (3500-7000 mg-hr; mean, 5500 mg-hr), respectively. The corrected 5-year survival rate for stage Ia was 76% and for stage Ib 72%. Grade had a profound effect on survival; corrected 5-year survival for G1 was 77%, for G2 68%, and for G3 53%, respectively. The total failure rate was 24% (40/171). Most of the recurrences occurred in the pelvis (35/171): uterus, 22; vagina, 9; rectum, 2; and bladder, 1. One patient had both vaginal and uterine failure and five had distant metastases (four abdominal and one pulmonary). No difference was seen in the failure rates of stage Ia and stage Ib patients. No major complications (necessitating hospital care or delay of treatment) were seen. Our findings suggest that for patients with stage I endometrial cancer who are unfit for surgery, intracavitary low-dose-rate radiation therapy alone is an effective alternative treatment with a low risk of complications. PMID- 1752490 TI - Endometrial carcinoma: transvaginal ultrasonography prediction of depth of myometrial invasion. AB - Myometrial invasion greater than 33% negatively affects the prognosis of endometrial carcinoma. Since the endometrium is readily differentiated from myometrium via high-resolution transvaginal sonography (TVS), this prospective study was undertaken to evaluate the efficacy of TVS in determining the depth of myometrial invasion in women with endometrial adenocarcinoma. Eighteen subjects underwent TVS utilizing 5.0- and 7.5-MHz probes by a single examiner blinded to stage and grade of adenocarcinoma. Predicted TVS ratios were categorized as less than 33% or greater than or equal to 33% and compared to actual histologic invasion. Ultrasound predicted that TVS ratios greater than or equal to 33% are significantly associated with deep (greater than 33%) histologic invasion (P less than 0.01, Fisher's test). When histologic invasion was greater than or equal to 33%, TVS was 100% accurate with no false negatives. The two cases in which TVS ratios erroneously indicated invasion greater than or equal to 33% contained adenomyosis and leiomyomas. TVS is a highly accurate and convenient method for preoperatively evaluating myometrial invasion. Potentially this evaluation could influence the selection of therapy for poor-surgical-risk candidates or direct appropriate referral of patients with deeper invasion to a gynecologic oncologist. PMID- 1752491 TI - Mitomycin-C/5-FU and radiation therapy for locally advanced uterine cervical cancer. AB - To assess the feasibility and effectiveness of combined therapy on locally advanced cervical cancer, we entered 38 patients into a study. The patients were treated with mitomycin-C (10 mg/m2) on Days 1 and 30 and 5-FU (1000 mg/m2) on Days 1 to 4 and Days 30 to 33. In 5 weeks 4500-5000 cGy was given concurrently, followed by radioactive implants. Twenty-six patients had an early-stage disease (IB-IIB) and twelve had a late-stage disease (IIIB-IVA). Eighty-seven percent (33/38) of the patients had a tumor measuring 5 cm or more. The other 5 patients with a tumor size under 5 cm had biopsy-proven positive pelvic nodes; 2 of these 5 patients had a pretherapy hysterectomy. Tumor response, complete (CR) vs partial (PR), was assessed in 36 patients 3 months after completion of therapy. A CR was noted in 80% (29/36) of the patients. The PR status conferred a detrimental effect on the pelvic disease control (PDC), disease-free survival (DFS), and survival (S) while late stage correlated with the development of distant metastases (DM) and a poor DFS. PDC was obtained in 93% (27/29) of the patients who had a CR, as compared to only 43% (3/7) of those with a PR (P = 0.0228). The DFS and S rates were 59 and 77% for patients with a CR and 21 and 19% for those with a PR; respective P values were 0.0340 and 0.0002. Eleven percent (3/26) of the patients with an early stage developed DM, as compared to 50% (6/12) of those with late stage, (P = 0.0016). The DFS rates were 80 and 37% for patients with an early and late stage, respectively (P = 0.0141). Four patients developed transient neutropenia and one had transient thrombocytopenia. The second dose of mitomycin-C was omitted in 4 patients due to persistent neutropenia in 3 and to transfusion-related hepatitis in 1. Two percent (5/21) of the patients who had a staging laparotomy developed wound dehiscence. Three patients developed non-cancer-related small bowel obstruction requiring surgery. We concluded that this combined regimen was well tolerated. Although it was effective in controlling the cancer in the pelvis, this regimen failed to control DM in late-stage patients. PMID- 1752492 TI - Flow cytometric DNA analysis versus cytology in the evaluation of peritoneal fluids. AB - The use of flow cytometric DNA analysis as an adjunct to cytology in peritoneal fluid evaluation was studied. One hundred ninety-five fluids from 193 gynecologic patients were subjected to both DNA analysis and cytologic examination. It was found that 117/195 (60%) had invasive malignancies (50 ovarian, 48 endometrial, 17 cervical, and 2 miscellaneous); 34/117 (28%) patients with malignancies were positive by cytology, and 10/117 (8.5%) were positive (aneuploid) by DNA analysis. Of 34 cytologically positive cases, 7 (21%) were DNA positive, 25 (74%) were DNA negative, and in 2 (6%) insufficient cells were obtained. Only 3 fluids (3%) from malignancies were positive by flow cytometry and negative by cytology (1 stage I ovarian cancer, 1 stage I endometrial cancer, and 1 stage III ovarian cancer). No false-positive cytology and one probable false-positive flow result was obtained. If only those patients with histologically documented peritoneal involvement are considered, 29/43 (65%) had positive cytology and 8/43 (19%) had a positive flow result. We conclude that: (1) the high false-negative rate of flow cytometry (79%) versus cytology in this study may be related to a high percentage of diploid cancers, specimen preparation, or histogram interpretation, and (2) flow cytometry rarely adds to cytologic evaluation and is probably best reserved for use only in selected cases. PMID- 1752493 TI - Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract. AB - Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control. PMID- 1752494 TI - Phase II trial of thio-TEPA in relapsed and refractory ovarian carcinoma. AB - On the basis of a Phase I reevaluation of thio-TEPA in which 3 of 9 patients with ovarian carcinoma responded, we instituted a Phase II study at high doses. Fourteen patients with a histologic diagnosis of epithelial carcinoma of the ovary, who had received at least one prior cisplatin-based regimen, were entered. Thio-TEPA was initially administered intravenously at a dose of 65 mg/m2 every 4 weeks, but was reduced to 50 mg/m2 after severe myelotoxicity developed in the first 5 patients. In 4 patients stable disease lasted 3, 4, 5, and 9 months; 10 patients progressed. There were no objective responses. At this dose and schedule, thio-TEPA has a response rate less than 20% in ovarian cancer patients previously treated with cisplatin. PMID- 1752495 TI - Specimen findings and survival after preoperative 252Cf neutron brachytherapy for stage II cervical carcinoma. AB - Twenty-seven patients with operable Stage II cervical cancer with a mean diameter tumor of 8.0 cm were studied in a feasibility study using preoperative 252Cf implants plus whole-pelvis radiation to 45 Gy followed by extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy 4 to 6 weeks later. Hysterectomy specimens were studied by a set protocol. With the protocol used, 13/27 (51%) specimens and abdominal stagings were negative for residual tumor. The survival rate for the patients with negative findings was 93% at 5 years. In 14/27 (49%) patients the specimens were positive for residual tumor. In contrast, the 5-year survival rate for this group was 46% (P less than 0.001). In these patients several interrelated factors were determined to be of importance, i.e., (1) tumor size greater than 8 cm in maximum diameter, (2) positive or negative residual tumor status, and (3) total dose of radiation given. Survival was lower for larger tumors and specimens were more likely to show residual tumor. A lower treatment dose led to more positive specimens, as well as to poorer survival. While the patients with Stage II disease fared very well when negative specimens were found, further prospective studies of the appropriate treatment for those with positive tumor specimens are needed. PMID- 1752496 TI - The effect of megestrol acetate on interleukin-1 activity. AB - The current study investigates the effect of megestrol acetate, a synthetic progestin, on the activity of interleukin-1. Murine thymocytes were suspended in vitro and stimulated with varying concentrations of interleukin-1. [3H]Thymidine uptake was observed as an index of thymocyte proliferation. A dose-dependent increase in [3H]thymidine uptake was observed with increasing concentrations of interleukin-1. When megestrol acetate was added to the solution, a marked suppressive effect was observed. Higher doses of megestrol acetate had a greater suppressive effect on thymocyte proliferation. Additional investigation is required to further delineate the potential systemic effects of megestrol acetate. PMID- 1752497 TI - Pretherapeutic scalene lymph node biopsy in ovarian cancer. AB - To study scalene lymph node involvement in ovarian cancer, 37 patients with this disease underwent pretherapeutic open sampling of the left scalene fat tissue. Only 1 patient had a palpable supraclavicular mass. Positive scalene nodes were found in 7 (22%) of 32 patients with stage III or IV disease. Three of four patients with positive scalene nodes also had both positive pelvic and positive paraaortic nodes; one patient with stage IV disease had negative pelvic and paraaortic nodes. Demonstration of scalene node involvement per se currently does not alter the management of patients with ovarian cancer, although patients with occult involvement of the scalene nodes could be considered ineligible for intraperitoneal chemotherapy. PMID- 1752498 TI - Concentrated albumin infusion as an aid to postoperative recovery after pelvic exenteration. AB - Twenty-eight patients underwent pelvic exenterations for gynecologic malignancies between June 1986 and June 1989. The postoperative fluid and electrolytes were managed by one of two regimens. One group of 10 patients was given concentrated 25% albumin infusion for the first 16 hr after surgery in addition to maintenance intravenous crystalloid solution according to ideal body weight. The second group of 18 patients received only a standard crystalloid solution. The albumin infusion group was found to have a more stable postoperative course as evidenced by less fluid boluses (P less than 0.01), fewer electrolyte bolus requirements (P less than 0.01), and easier management of blood pressure and urine output. There was a 50% decrease in total fluid requirement, a higher mean right atrial pressure (P less than 0.05), and a lower maintenance intravenous fluid rate (P less than 0.01). As a consequence, central hyperalimentation was started earlier (P less than 0.01) and the albumin infusion group left the Intensive Care Unit sooner than the non-albumin infusion group. There was not a single instance of clinical fluid overload with this slow infusion technique. Thus, concentrated albumin infusion was beneficial in the acute fluid management of these difficult patients. PMID- 1752499 TI - The prognostic importance of site and type of radiation-induced bowel injury in patients requiring surgical management. AB - A multivariate analysis was performed to determine the outcome, and factors prognostic for outcome, in 57 patients requiring surgical intervention for radiation bowel injury. The actuarial 2- and 5-year cause-specific survival (CSS) was 76 and 74%, respectively, with a median follow-up of 62 months for the survivors. The median time from surgery to death from complications was 4 months. Identified sites of injury were both large and small bowel. The types of injury were defined as stricture, perforation, inflammation, and fistula. At surgery 9 patients had more than one site, and 15 patients had more than one type of injury. Cox proportional hazards regression models relating survival to individual patient characteristics were constructed using surgical procedure, radiation-surgery interval, age, stage, radiotherapy technique and dose, and the individual sites and types of injuries. Only the site of injury was found to be of prognostic significance for CSS (P less than 0.03). However, when the site and type of injury were recoded as single or multiple, Cox regression analysis found both the site (P = 0.008) and the type (P = 0.02) of injury to be statistically significant for CSS (favoring single sites and types). Stepwise multivariate regression analysis found type of injury to be insignificant when site of injury was already in the model. Ileal damage was associated with the lowest CSS of any single site of injury (56%) and also appeared to be responsible for the poor CSS of those with multiple sites of injury (46%). PMID- 1752500 TI - Masculinizing sclerosing stromal tumor of the ovary during pregnancy. AB - Sclerosing stromal cell tumors of the ovary are an uncommon neoplasm that usually does not produce hormonal imbalances. Most patients showing a hormonal effect from this lesion have had menstrual cycle disturbances. Infertility and endometrial hyperplasia have also been described. One other reported case had masculinizing effects. Other authors have documented elevated levels of both estrogenic and androgenic hormones that corrected after surgery. A case of a pregnant 27-year-old Caucasian with hirsutism on her chin and neck and a male suprapubic hair pattern is presented. Elevated androstenedione, dehydroepiandrosterone, and free testosterone levels were present. A 3-cm left ovarian mass was excised and identified as a sclerosing stromal tumor. The histologic features included a pseudolobular pattern with focal areas of sclerosis and a two-cell population of spindled and polygonal cells. Immunohistochemical studies showed a positive vimentin reaction, weakly positive desmin and muscle-specific actin stains, and a negative cytokeratin stain. Following surgery the hormone levels returned to normal and the hirsutism resolved. A normal female infant without evidence of masculinization was delivered from the patient at term. PMID- 1752501 TI - Breast cancer and second primary ovarian cancer in dermatomyositis. AB - We report six female patients with breast cancer who developed dermatomyositis and compare our data with those from other reports. The development of dermatomyositis in two patients led to the discovery of a second primary ovarian carcinoma, whereas the development of dermatomyositis in another two patients led to the discovery of recurrent breast cancer. In three patients the diagnosis of dermatomyositis preceded the diagnosis of breast cancer, while the rest developed dermatomyositis after the diagnosis of breast cancer. A parallel clinical course of dermatomyositis and breast cancer was seen in only one patient. Coexisting dermatomyositis and breast cancer is a rare phenomenon, and dermatomyositis that develops during the course of breast cancer may indicate the occurrence of a second primary malignancy or recurrent breast cancer. The onset of dermatomyositis may precede, coincide with, or follow the diagnosis of breast cancer. The clinical course of dermatomyositis sometimes, but not always, parallels the course of breast cancer. There are no specific clinical or laboratory markers to distinguish patients with dermatomyositis who have malignancy from those without cancer. PMID- 1752502 TI - Cervical cancer metastatic to the breast: a rare presentation of tumor dissemination. AB - Metastatic disease presenting in the mammary gland from gynecologic malignancies is a rare occurrence. A case of metastatic adenosquamous carcinoma of the cervix presenting as an inflammatory breast lesion is reported. Metastases within the breast have distinct clinical, radiographic, and histologic features and should be suspected in a patient with a breast mass and a known extramammary primary. As with other distant metastases of cervical cancer, mammary gland involvement portends a poor prognosis. PMID- 1752503 TI - Radiation myelitis: a complication of concurrent cisplatin and 5-fluorouracil chemotherapy with extended field radiotherapy for carcinoma of the uterine cervix. AB - Radiation myelitis is a rare but serious complication of radiation therapy. The total dose of radiation to the spinal cord required to cause myelopathy is greater than 50 Gy when the treatment is administered in 25 or more fractions; however, recent evidence has suggested that the concurrent use of chemotherapy may decrease the tolerance of the spinal cord to radiation. This report describes a case of radiation myelitis in a patient after concomitant fluorouracil/cisplatin chemotherapy and extended field radiotherapy for stage IIA adenosquamous cell carcinoma of the uterine cervix metastatic to the para-aortic lymph nodes. PMID- 1752504 TI - Non-Hodgkin's lymphoma during pregnancy. AB - A rare case of non-Hodgkin's lymphoma stage IE complicating pregnancy is presented. The diagnosis was made by biopsy at 28 weeks gestation and treated with 2635 rad of external radiotherapy with abdominal and pelvic shielding beginning at 30 weeks gestation. Following delivery, the patient received combination chemotherapy and is disease-free 6 years later. The baby, weighing 2015 g, was delivered by cesarean section at term. The effects of radiotherapy on a fetus are reviewed and the factors that were considered in the treatment of this patient are discussed. Radiotherapy with protective shielding can be an effective initial modality of treatment in this setting. PMID- 1752505 TI - Three cycles of chemotherapy followed by primary cytoreductive surgery for unresectable ovarian cancer. AB - Definitive primary cytoreductive surgery was achieved at second laparotomy after three cycles of combination chemotherapy (cisplatin and cyclophosphamide) in three patients who presented with unresectable disease at our Ovarian Tumor Unit. The ovarian cancer was inoperable at the first laparotomy and no surgical procedure was performed other than biopsy of malignant tumor to confirm the diagnosis. Following interventional surgical cytoreduction the patients were given a further six courses of combination chemotherapy and then maintained for a further six cycles on oral chlorambucil. Two patients are disease free at 17 and 21 months, respectively, while the other patient has cytological evidence of malignancy but no other clinically detectable tumor deposits at 27 months. PMID- 1752506 TI - [Multiple myeloma. Mechanisms of proliferation and neoplastic progression and their clinical implications]. PMID- 1752507 TI - [Nosographic profile of thrombocytopenia]. PMID- 1752508 TI - [Platelet immunology: diagnostic aspects of thrombocytopenia]. PMID- 1752509 TI - [Idiopathic thrombocytopenic purpura: therapeutic aspects in the adult]. PMID- 1752510 TI - [Thrombocytopenia: therapeutic aspects in the child]. PMID- 1752511 TI - [HIV-positive thrombocytopenia]. PMID- 1752512 TI - [New anthracyclines and multidrug resistance]. PMID- 1752513 TI - [The immunophenotype in leukemia]. PMID- 1752514 TI - [Physiopathology of erythrocyte membrane transport]. PMID- 1752515 TI - [Membrane processes in the aging of the human red cells]. PMID- 1752516 TI - [Endogenous erythrocyte proteolysis: a new approach to the study of membrane physiopathology]. PMID- 1752517 TI - [Epidemiology of the principal hematologic diseases and health needs]. PMID- 1752518 TI - [Teaching hematology to medical students]. PMID- 1752519 TI - [Teaching hematology in specialty schools]. PMID- 1752520 TI - [Nuclear magnetic resonance in onco-hematology]. PMID- 1752521 TI - [Cellular mechanisms in the pathogenesis of thrombosis]. PMID- 1752522 TI - [New diagnostic methods for the pre-thrombotic state]. PMID- 1752523 TI - [Thrombosis and anti-tumor chemotherapy]. PMID- 1752524 TI - [Systemic effects of thrombolytic therapy]. PMID- 1752525 TI - [The human hematopoietic stem cell, normal and leukemic]. PMID- 1752526 TI - [Clinical use of hematopoietic growth factors]. PMID- 1752527 TI - [Minimal residual disease]. PMID- 1752528 TI - [Autotransplantation in acute nonlymphoid leukemia]. PMID- 1752529 TI - [Bone marrow transplantation from non-consanguineous compatible donors: current state and prospects]. PMID- 1752530 TI - [Thrombocythemia. General considerations]. PMID- 1752531 TI - [Essential thrombocythemia: in vitro study of megakaryocytopoiesis]. PMID- 1752532 TI - [Essential thrombocythemia: clinical aspects]. PMID- 1752533 TI - [Essential thrombocythemia: pregnancy]. PMID- 1752534 TI - [Essential thrombocythemia: conventional therapy]. PMID- 1752535 TI - [Essential thrombocythemia: antiaggregants]. PMID- 1752536 TI - [Essential thrombocythemia: therapy with alpha interferons]. PMID- 1752537 TI - [Transfusion safety]. PMID- 1752538 TI - [Autotransfusion: a critical review]. PMID- 1752539 TI - [Chronic myeloid leukemia: progress and prospects]. PMID- 1752540 TI - [Blood component therapy today]. PMID- 1752541 TI - [Immunologic changes in polytransfused hemophiliacs]. PMID- 1752542 TI - [Hematologic manifestations of HIV disease]. PMID- 1752543 TI - [Bone marrow transplantation in thalassemia]. PMID- 1752544 TI - [Therapy of adult acute lymphoblastic leukemia]. PMID- 1752545 TI - [Myelodysplastic syndromes: mechanisms of transformation and neoplastic progression and their clinical implications]. PMID- 1752546 TI - [Role of peptide regulatory factors in the proliferation of leukemic blasts]. PMID- 1752547 TI - [Patient-controlled i.v. morphine for acute postoperative pain]. AB - The use of patient-controlled i.v. analgesia for postoperative pain relief in 60 cases is described. 0.1% morphine was given by Bard or Graseby microprocessor. After a loading dose of 2-6 mg, the pump delivered a bolus of 0.8-1.5 mg of morphine every 8-12 min. The dosages necessary to provide good analgesia varied from 30-85 mg (mean 48). Good pain scores of 0-2 (on a scale of 5) were obtained in 92%. The method was also found satisfactory by the families and health care providers, and is highly recommended for control of postoperative pain. PMID- 1752548 TI - [Osteoarticular tuberculosis in a general hospital]. AB - The status of osteoarticular tuberculosis in recent years was studied. 82 cases diagnosed here between 1951-1985 were surveyed. The disease was more common among East European Jews (38%) and among young people: the mean age was 36 years and the highest incidence was in the third decade. A secular tendency to "aging" was noted, as in later years the mean age increased. However, there was also a secular decrease in incidence, explained by a progressive decrease in immigration to Israel. The disease affected most commonly the spinal vertebrae and the weight bearing joints. There was an average delay of 19 months between onset of symptoms and/or signs of the disease and its diagnosis. PMID- 1752549 TI - [Tuberculosis of the spine and ribs]. AB - Tuberculosis of the spine or ribs is uncommon, occurring in less than 1% of patients with tuberculosis (TB). 2 women are presented who recently immigrated from Ethiopia and India, respectively. One, aged 55, presented with chest pain, fatigue and several masses under the skin of the scalp. Chest X-ray and CT scan suggested Pancoast tumor, and the lateral parts of the first 2 right ribs were absent. The origin of the patient, clinical findings and positive PPD suggested TB of the ribs and anti-TB therapy resulted in cure. The diagnosis was later confirmed by a positive culture. The other woman, aged 68, presented with fatigue, mild abdominal pain and axillary lymphadenopathy. The PPD was positive and X-ray showed widening of the mediastinum. A caseating granuloma with Langhans epithelioid cells was found in a lymph node. Flaccid paraparesis developed before therapy was started. CT scan showed a typical picture of TB affecting the T3-T6 vertebrae. Drainage of a cold abscess of the spine via the anterior approach was followed by anti-TB therapy. Culture of a biopsied lymph node and of pus obtained at operation confirmed the diagnosis of TB. The patient died 2 months later from gastrointestinal bleeding. Awareness of the unusual presentations of various forms of TB is mandatory in countries with immigration from countries in which TB is still common. PMID- 1752550 TI - [Oral contraceptive lowers serum magnesium]. AB - The effect of an oral contraceptive on serum magnesium was assessed in a group of 32 women, mean age 24.2 years, attending a family planning clinic. The pill contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. As in pregnancy and during estrogen replacement in postmenopausal women, the contraceptive pill lowered serum magnesium (from a mean of 0.82 mmol/l, to 0.61 mmol/l in 6 months). Larger studies may determine whether routine dietary magnesium supplementation is necessary in oral contraception. PMID- 1752551 TI - [Extracardiac malignancy presenting with cardiac tamponade]. AB - We describe a 65-year-old man with cardiac tamponade as the first manifestation of malignancy. Biochemical, bacteriological and cytological examinations of the pericardial fluid were not diagnostic. Abdominal CT showed a mass in the right adrenal and fine needle aspiration revealed metastatic carcinoma. The patient died 4 months later with the clinical and roentgenological picture of bronchogenic carcinoma. PMID- 1752552 TI - [Evaluation of verapamil for hypertension by an isometric exercise test]. AB - Since the resting blood pressure (BP) does not predict round-the-clock values, in order to evaluate the disease and its response to treatment BP should be measured during exertion. Verapamil, either 120 mg or 160 mg, twice daily, was given to 60 hypertensives at rest and during isometric effort, according to our previously reported protocol. There was a significant response (p less than 0.005) to the treatments. Sustained release verapamil, 240 mg once a day, reduced systolic and diastolic BP significantly in 38 of 45 hypertensives at rest and during isometric effort. A simple, inexpensive, cost-effective, hand-grip method is strongly recommended as an integral part of treatment evaluation. The combination of highly effective drugs together with a simple method of BP evaluation may result in improved long-term treatment. PMID- 1752553 TI - [Complications of low-dose amiodarone]. AB - Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated. PMID- 1752554 TI - [Acute fulminant hepatic failure after short-term amiodarone]. AB - Acute liver failure occurred in a 59-year-old man with congestive heart failure within 4 days of oral loading with amiodarone. Hepatic toxicity of amiodarone leads to 2 histologic pictures: pseudo-alcoholic hepatitis and phospholipoidosis. Immune mechanisms are possible in amiodarone hepatotoxicity. PMID- 1752555 TI - [Preajmaline-induced cholestatic hepatitis]. AB - 2 cases of cholestatic hepatitis due to preajmaline recovered when the drug was stopped. One was a 40-year-old woman, and the other a 74-year-old man whose jaundice lasted for 8 months. Approximately 40 patients with preajmaline-induced hepatitis have been described in the literature. All recovered except 1, who developed biliary cirrhosis while using preajmaline in conjunction with other hepatotoxic drugs. PMID- 1752556 TI - [Sex determination--has the puzzle been solved?]. PMID- 1752557 TI - [Recombinant erythropoietin--clinical use and future prospects]. PMID- 1752558 TI - [Treatment of arrhythmias beyond CAST]. PMID- 1752559 TI - [Intracavernous injections for the treatment of erectile dysfunction]. PMID- 1752560 TI - [Malpositioning of central venous catheters]. PMID- 1752561 TI - [CNS toxicity of antineoplastic drugs]. PMID- 1752562 TI - [Popliteal artery entrapment syndrome]. PMID- 1752563 TI - [History of anorexia nervosa and bulimia nervosa]. PMID- 1752564 TI - [Recent aspects of post-operative pain control]. PMID- 1752565 TI - [The streaming liver]. PMID- 1752566 TI - [Parasites and autoimmunity]. PMID- 1752567 TI - [Recent trends in the management of cancer of the vulva]. PMID- 1752568 TI - [Immunological effects of vitamin A]. PMID- 1752569 TI - [Pectus excavatum: only a cosmetic defect?]. PMID- 1752570 TI - [Is there a linkage between mental illness and traffic accidents?]. PMID- 1752571 TI - [New concepts in bronchial asthma]. PMID- 1752572 TI - [Surgical treatment of urinary stress incontinence in females]. PMID- 1752573 TI - [Suspected epilepsy: a dangerous diagnostic term]. PMID- 1752574 TI - [Discovery of AIDS virus behind the scenes]. PMID- 1752575 TI - [Shortness of breath, left hemiparesis and leukocytosis after coronary bypass]. PMID- 1752576 TI - [Moh's micrographic surgery: first experience in Israel]. AB - Moh's micrographic surgery is a method by which cancer of the skin may be excised under complete microscopic control. It consistently offers the highest cure rate in the treatment of malignancy of the skin, while the least amount of uninvolved tissue is sacrificed. This, the first center for Moh's micrographic surgery in Israel, started functioning in 1989. The first 50 patients included 33 women (average age 50.7 years) and 17 men (average age 60.6 years) suffering from basal cell carcinoma of the face. 56% of the patients were referred for Moh's surgery after failure of other primary treatments, and the rest were referred due to the problematic location of the lesion or its size. 13 patients (28%) were referred after previous treatment with solcoderm (Mardi's method). In these patients the lesions were especially deep and aggressive. PMID- 1752577 TI - [Surgical treatment of urinary stress incontinence in women]. AB - 32 women with genuine stress urinary incontinence were operated on via the transvaginal approach during 1989-1990. They ranged in age from 27-72 years, with a mean of 55.7. In 26, in addition to the urine leakage, vaginal wall prolapse of various degrees was diagnosed. 6 underwent Raz modified Pereyra bladder neck suspension, 26 had Raz 4-corner bladder and bladder neck suspension, and in 17 rectocele and perineal repair were also performed. 2 with uterine prolapse also underwent vaginal hysterectomy. At follow-up 2-12 months later 29 of the 32 were completely cured of stress incontinence (90.6%). In 7 urge incontinence persisted in various degrees, and 3 had developed urge incontinence de novo. All but 1 of them responded favorably to anticholinergic medication. There were postoperative complications in 5 (15.6%), including wound infection that required removal of Prolene sutures in 2, urethrovaginal fistula requiring reoperation in 1, perioperative myocardial infarction in 1, and in 1 voiding dysfunction initially treated with self-intermittent catheterization, but later cured by removal of a pair of Prolene sutures. PMID- 1752578 TI - [Fractures of the proximal femur]. AB - 907 patients were operated on for fracture of the proximal femur in 1986-1987 and were then followed for an average of 7 months. There was a relatively high rate of complications in those over the age of 71, in whom mortality reached 15.5%, while the overall mortality was 6.8%. There was also a high rate of complications in those operated 3 or more days after the fracture had occurred. In those up to the age of 60, the ratio of males to females was almost 1 to 1, but in those over 80 the ratio was 1 to 4. The mortality of males was higher (9.2%) than that of females (5.5%). In trochanteric fractures treated by various methods of rigid fixation there were no problems of union or delayed union. Early mobilization and early discharge from hospital reduced mortality and complications. PMID- 1752579 TI - [Morbidity in primary care clinics of 29 kibbutzim--prospective study]. AB - All consultations and diagnoses in the clinics of 29 kibbutzim during the 12 month period, March 1981-February 1982, were analyzed. In these clinics there is physician-nurse teamwork and the nurse handles independently certain types of consultations which in the regular Kupat Holim clinic would ordinarily be handled by a physician. The total study population was 15,605, and there were 62,950 consultations during the observation period, giving an average annual rate of 4.03 per person. More than 40% of the consultations were with nurses. The distribution of diseases by the 18 main diagnostic groups of the International Classification of Diseases was compared with that in 3 earlier primary care surveys in Israel and that in the large general practice survey in Britain for the years 1981 and 1982. There were no marked differences between the morbidity patterns of this survey and those of the others. The morbidity patterns were typical for those found nowadays at the primary care level in developed countries. With greater life expectancy in industrialized societies, chronic degenerative diseases and particularly cardiovascular diseases, have increased. This is reflected in more frequent visits to primary care clinics. The proportion of these visits is slightly lower in this survey than in the others due to the younger age profile of the kibbutz population. PMID- 1752580 TI - [Pulmonary edema complicating upper airway obstruction]. AB - A 40-year-old man who developed acute pulmonary edema following relief of upper airway obstruction is presented. The mechanism of pulmonary edema associated with upper airway obstruction is complex and not fully understood. It is therefore difficult to predict which patients will develop pulmonary edema during or after the relief of obstruction. PMID- 1752581 TI - [Central retinal artery occlusion in a young man]. AB - Central retinal artery occlusion (CRAO) is uncommon in those younger than 50. We present a 42-year-old man who complained of sudden loss of vision in the left eye. Fundus examination showed typical findings of CRAO. Extensive medical work up showed no evidence of diabetes or of cardiovascular, hematologic or collagen disease. However, a malignant tumor of the right testis was found, with metastases in the lung, retroperitoneal lymph nodes and brain. The right testis was resected and chemotherapy and brain irradiation resulted in remission during a follow-up of 2.5 years. The differential diagnosis of CRAO in younger patients is difficult. We believe that metastases from the primary tumor were the cause of CRAO in our patient. The possibility of malignancy with metastatic spread causing CRAO should be considered, particularly in relatively young patients with no other evidence of systemic disease. PMID- 1752582 TI - [Captopril-induced liver dysfunction]. AB - Captopril is widely used for congestive heart failure and arterial hypertension. Its main side effects are cough, neutropenia, and renal injury. Liver dysfunction has rarely been described. We present a 71-year-old man with an acute myocardial infarction who developed high fever and progressive disturbance of liver function tests, hepatocellular and cholestatic, after beginning captopril. When other, more likely causes for his condition were ruled out, captopril was discontinued and the fever and liver dysfunction then quickly resolved. We recommend periodic laboratory follow-up in patients treated with angiotensin-converting enzyme inhibitors. PMID- 1752583 TI - [Management of attention deficit and hyperactivity disorder]. PMID- 1752584 TI - [Medical malpractice in Israel court judgements and defensive medicine: is it possible to restore trust between patients and physicians? Part II. Defensive medicine]. PMID- 1752585 TI - Semen finger print. AB - A correlation between testosterone (T) and dihydrotestosterone (DHT) exists in seminal plasma. These androgens play a role in sperm maturation. The T/DHT ratio is different from one person to the other, due to the heterogenicity of seminal plasma which stems for the most part from the male accessory sex glands, the prostate and seminal vesicles, and also from the 'epididymo-testicular unit'. This ratio is useful in identifying the person's semen. Consequently, the steroid values from assailant semen or accused persons and semen on the victim's clothes are of cardinal importance in matching. The results reported include data on the validation of this technique as a tool for semen identification. Coital and masturbated semen were correlated, and consecutive coital semen were also analysed. It may be concluded that the T/DHT value is specific for each person. PMID- 1752586 TI - Evaluation of a method for simultaneous quantification of codeine, ethylmorphine and morphine in blood. AB - Codeine, ethylmorphine and morphine are the most commonly detected opiates in forensic blood samples in Norway. A method for the simultaneous quantification of these opiates utilizing solid phase extraction and gas chromatography-mass spectrometry has been evaluated. The detection limits were 0.026 mumol/l for codeine, 0.025 mumol/l for ethylmorphine and 0.032 mumol/l for morphine (corresponding to 7.8, 7.8 and 9.1 micrograms/l, respectively). The analytical variations at concentrations of 1.0 mumol/l codeine, 1.0 mumol/l ethylmorphine and 0.5 mumol/l morphine were less than 5%. PMID- 1752587 TI - In vitro loss of potassium from erythrocytes during the 0-108 h postmortem period in rats: relationship between potassium loss and postmortem interval. AB - A simple technique was employed for measurement of potassium loss (K(los)s) from normal and from postmortem rat erythrocytes during controlled exposure to physiologically isosmotic NaCl solution. Potassium loss from the cells decreased in a (non-linear) time-related manner during the 0-108 h postmortem period; expression of the data in the form of a double logarithmic plot (log K(loss) versus log postmortem interval (PMI) linearized the relationship between 18 and 108 h post mortem (r = -0.86; P less than 0.001 (n = 24)). Experimental data revealed that the observed postmortem changes in K(loss) were associated with and probably resulted from, the postmortem decrease in magnitude of the potassium concentration gradient across the erythrocyte membrane. Attention is drawn to the possibility of utilizing measurements of in vitro loss of potassium from erythrocytes as a means of estimating time elapsed since death. PMID- 1752588 TI - Gas chromatographic-mass spectrometric analysis of buflomedil hydrochloride in biological samples after acute intoxication. AB - Two cases of acute intoxication of buflomedil hydrochloride are reported. The analysis of this compound was performed by an Extrelut extraction followed by a gas chromatographic-mass spectrometric determination. Analytical parameters of linearity, reproducibility and specificity were satisfactory. PMID- 1752589 TI - Neurosurgical vascular complications associated with aneurysm clips evaluated by postmortem angiography. AB - Neurosurgical vascular complications were evaluated by postmortem angiography in a consecutive prospective series of 63 patients in Helsinki who suffered a fatal outcome following neurosurgery for ruptured intracranial aneurysm. Operative vascular complications were revealed in 28 (44%) of the cases. Massive intraoperative bleeding resulting from rupture of the aneurysm or adjacent major artery during dissection or clip application complicated the operation in 16 (25%) patients. Clip-induced obstruction of cerebral arteries was detected by angiography in seven cases (11%). In six of the patients an adjacent cerebral vessel was accidentally clipped. In one case a kinking of the clip had caused obstruction of the right anterior cerebellar artery with resulting frontal infarct. A combination of rupture of the internal carotid artery and accidental ligation of the left posterior cerebellar artery occurring simultaneously during the clipping of a ruptured basilar aneurysm was detected in one patient (2%). Other types of complication were revealed in four cases (6%): detachment of clip with re-bleeding; clipping of an uninvolved aneurysm instead of the ruptured one; displacement of the clip beneath the ruptured aneurysm. Operations on ruptured basilar artery aneurysm were significantly (P less than 0.01) more prone to complications. The results indicate that operative vascular complications play a significant role in the mortality of aneurysm patients. Post-mortem angiographic technique with contrast medium that vulcanizes at room temperature is particularly suitable for demonstration of the haemodynamic significance of clip induced cerebrovascular accidental occlusions, and is the only method at autopsy to reveal an occlusion caused by a kinking of a properly placed aneurysm clip. PMID- 1752590 TI - The analysis of quaternary ammonium compounds in human urine by direct inlet electron impact ionization mass spectrometry. AB - An accurate and rapid screening test for nine quaternary ammonium compounds (suxamethonium chloride, pancuronium bromide, ambenonium chloride, benzethonium chloride, distigmine bromide, methylbenactyzium bromide, neostigmine bromide, propantheline bromide and pyridostigmine bromide) by direct inlet electron impact ionization mass spectrometry (DI/EI-MS) was investigated. Each compound was extracted from urine as an ion pair with KI3 into dichloromethane. The reliability of the identification of these compounds was verified by the mass chromatographic analysis of their characteristic fragment ions. The analysis of these drugs by DI/EI-MS could be performed within 5 min. The detection limits were between 20-150 ng/ml for the nine compounds. This method appears to be efficient, rapid and suitable as a screening procedure for the quaternary ammonium compounds found in urine. PMID- 1752591 TI - A new biochemical method for estimation of postmortem time. AB - Hypoxanthine (Hx) is formed by hypoxic degradation of adenosine monophosphate (AMP) and might be elevated due to antemortem hypoxia. However, it also increases after cessation of the life processes. Until now measurements of potassium in corpus vitreous humor have been used by forensic pathologists to determine postmortem time. In this study the influence of postmortem time and temperature on vitreous humor Hx and potassium levels were compared. Repeated sampling of vitreous humor was performed in 87 subjects with known time of death and diagnosis. The bodies were kept at either 5 degrees C, 10 degrees C, 15 degrees C or 23 degrees C. Hx was measured by means of HPLC and potassium by flame photometry. In 19 subjects from whom samples were obtained within 1.5 h after death, the normal level of Hx could be estimated to be 7.6 mumol/l and that of potassium to be 5.8 mmol/l. The spread of the potassium levels measured shortly after death was much greater than for the corresponding Hx levels. In the four temperature groups the Hx level increased 4.2, 5.1, 6.2 and 8.8 mumol/l per h, respectively, whereas the corresponding figures for potassium were 0.17, 0.20, 0.25 and 0.30 mmol/l per h. The vitreous humor concentration of both Hx and potassium increases fairly linearly after death. The slopes are steeper with increasing temperature. Since the scatter of the levels is greater for potassium than for Hx, the latter parameter seems to be better suited for the determination of time of death in cases without antemortem hypoxia, especially during the first 24 h. PMID- 1752592 TI - The polymerase chain reaction and post-mortem forensic identity testing: application of amplified D1S80 and HLA-DQ alpha loci to the identification of fire victims. AB - The application of DNA typing methods after amplification by the polymerase chain reaction (PCR) of DNA derived from body tissues from charred fire victims was investigated. A total of 26 different tissue specimens from ten extensively burned individuals were analyzed. The samples included femoral muscle, psoas muscle, bone marrow and blood. The post-mortem period varied from 38 to 183 h. After amplifying the DNA by PCR from the various tissues, the D1S80 locus was analyzed with a high resolution polyacrylamide gel electrophoresis technique followed by silver staining and the alleles of the HLA-DQ alpha locus were detected by using a reverse dot blot format. All samples could be typed for both loci and the genotypes were consistent in the various tissues from each individual. A parentage test was performed in two cases and Mendelian inheritance of the alleles for both loci was observed. PMID- 1752593 TI - Recent status of the medical examiner system in Japan: demographic variation of medicolegal deaths in Hyogo Prefecture and uncertainty in medicolegal investigations conducted by medical practitioners. AB - The medical examiner system has been steadily abolished in Japan. Instead, medicolegal investigations are entrusted by the police to medical practitioners, who are not permitted to perform autopsies. The necessity for the medical examiner system was assessed through inquest records in Hyogo, one of the three prefectures which still have medical examiner systems. Standardized mortality ratios (SMRs) for accidents and suicides were negatively associated with population density, being high in rural areas with a large proportion of elderly citizens, while the SMR for natural deaths was high in urbanized areas and associated with the proportion of inquests to total resident deaths. The high proportion of inquests, however, did not always mean that inquest records were of good quality. Significant differences in the quality of medicolegal investigations seemed to exist between medical examiners and medical practitioners. That is, in order to certify the cause-of-death, medical examiners performed autopsies in about half of their cases, while only 2% of medical practitioner cases were subjected to autopsies. Medical practitioners, who certified the cause-of-death as "heart failure" without advising an autopsy, were regularly entrusted with inquests. It is likely that the causes-of-death for medicolegal cases may be questionable since more than 85% of all medicolegal deaths were investigated by medical practitioners, which may cause inaccuracy in at least 3-7% of mortality statistics. It is necessary to educate medical practitioners concerning the importance of mortality statistics and ICD and on the validity of autopsies, in order to obtain accurate mortality statistics from medicolegal cases. PMID- 1752594 TI - Simultaneous observation of catecholamine, serotonin and their metabolites in incised skin wounds of guinea pig. AB - In order to examine the vital reaction in wounds, catecholamines, serotonin (5 HT) and their metabolites in the incised skin wounds of guinea pigs were analyzed simultaneously by high-performance liquid chromatography (HPLC) using electrochemical detection (ECD). The principal changes in the levels of these compounds in vital wounds were as follows: a considerable decrease in norepinephrine (NE) content was observed 12-24 h after injury which persisted to at least 7 days. 3,4-Dihydroxyphenylacetic acid (DOPAC) decreased slightly for up to 30 min and then showed no significant difference compared with postmortem levels. Epinephrine and dopamine were barely detected by the HPLC-ECD method employed. 5-HT concentrations which showed an increase up to 24 h showed maximum levels 800 microns from the wound edge at 10 and 30 min after injury. 5 Hydroxyindoleacetic acid (5-HIAA) was significantly higher than the postmortem level over almost the entire period of these experiments. A 5-HIAA content of at least twice the postmortem level was observed 800 microns from the wound edge of a 10-min-old vital wound. Therefore, 5-HIAA is a likely candidate as a new marker for evaluating the vital reaction in wounds. The vital characteristics of NE, DOPAC, 5-HIAA and 5-HT in 10-min-old wounds persisted for up to 12 h at room temperature after death. These results suggest that the HPLC-ECD method used here is very useful for simultaneous examination of the vital reaction in wounds from the earliest to the later stages of the wound-healing period. PMID- 1752595 TI - Ofloxacin in human hair determined by high performance liquid chromatography. AB - A procedure is presented for quantitating ofloxacin (OFLX) in human scalp hair by high performance liquid chromatography (HPLC) with a fluorescence detector. An octadecylsilane (ODS) column was used and the mobile phase was a mixture of potassium phosphate buffer (pH 2.6) and acetonitrile. The recovery of OFLX was 90.9-93.8% and within- and between-run precisions were 0.35-1.41% and 1.41-5.49% as the coefficient of variation (CV), respectively, when 5-50 ng OFLX was added to 1 mg blank hair. The calibration curve was linear in the range of 0.5-50 ng/tube (0.5 ml). Interference with other quinolone derivatives could be avoided according to the difference in their retention times or fluorescence spectra. Several pieces of hair were obtained from each of twelve healthy male volunteers, who had taken OFLX (100, 300 or 900 mg total dose) over a 1-3 day period 2 weeks before the hair sampling. In all hair samples except one obtained from a volunteer, who had taken the lowest dose, the 2-cm long segments nearest the scalp contained OFLX (5-45 ng/mg hair), while the upper segments did not. A highly significant positive correlation was observed between the total dose and the concentration of OFLX in the 2-cm long hair segments. Such a positive correlation was also revealed in rat hair sampled after repeated i.p. administration of OFLX over a 5-week period. These results suggest that the measurement of OFLX in hair by the present method would be useful for testing patient compliance in clinical pharmacology as well as for application to forensic science. PMID- 1752596 TI - Solid phase extraction method for rapid isolation and clean-up of some synthetic pyrethroid insecticides from human urine and plasma. AB - A simple and rapid method for the isolation of seven synthetic pyrethroid insecticides (methothrin, fenpropathrin, cyhalothrin, permethrin, cypermethrin, fenvalerate, deltamethrin) with a solid phase extraction (SPE), utilizing Sep-Pak C18 cartridges, from human urine and plasma is presented. The detection of the insecticides was performed using a wide bore capillary gas chromatograph (GC) with flame ionization detection (FID). The insecticide-containing samples mixed with 70% methanol were directly applied to the cartridges and eluted with 2 ml chloroform. The recoveries using the cartridges were between 90-102% for urine and 81-93% for plasma. Mixing samples with 70% methanol prior to extraction, seems very useful for the screening of synthetic pyrethroid insecticides. PMID- 1752597 TI - Event-related brain potentials as indicators of visual recognition and detection of criminals by their use. AB - An event-related potential (ERP) was recorded, using photographs as stimuli, in 12 subjects for attended, 9 subjects for non-attended conditions and 14 subjects for a simulated criminal investigation. An ERP was detected only when a subject recognized a familiar image (target) mixed with other, unfamiliar images (non target), regardless of whether he was asked to attend to or neglect the target image. ERPs in the subject who watched each picture but tried to ignore the relevant picture (non-attended) were more activated at the parietal region than at the central region, in contrast with ERPs in the subjects who paid attention to each picture without trying to ignore the relevant picture (attended). In the simulated criminal investigation, only a simulated thief, but not a simulated innocent subject elicited ERP only after the picture of a criminal site or thing was intermingled with pictures bearing no relationship to the crime. These findings indicate that the ERP using photographs as stimuli is useful as an objective indicator of crime-relevance. PMID- 1752598 TI - New aspects of prolactin in human reproduction physiology. Tokyo, August 25, 1990. PMID- 1752599 TI - Role of angiotensin on paracrine prolactin release in the pituitary gland and its possible effects on ovarian function. AB - The present study was undertaken to investigate the role of angiotensin II (AII) in GnRH-induced PRL release on the paracrine interaction among anterior pituitary cells of young male rats. A 20-min perifusion with 100 nM GnRH increased PRL release (p less than 0.01) from pituitary cell aggregates, and GnRH-stimulated release of PRL was significantly suppressed by saralasin, a specific AII antagonist. The release of AI from pituitary cell aggregates was significantly (p less than 0.01) increased by GnRH. These data demonstrate that GnRH is capable of stimulating PRL release through a mechanism that may involve the release of angiotensin. It was also speculated that some factors released from pituitary cells, such as angiotensin, might be involved in the control of ovarian functions. As an approach to investigate this possibility, porcine anterior pituitary cells and ovarian granulosa cells were co-cultured on type 1 collagen membrane which permits the exchange of the substance with molecular weights less than 9,000. The growth and progesterone production of the granulosa cells co cultured with pituitary cells were significantly (p less than 0.05) greater than those of the cells cultured in monolayer fashion. Thus, the results of the present study revealed the biological significances of the paracrine system involving angiotensin between gonadotroph and lactotroph in pituitary cells and the direct effect of the factors derived from pituitary cells on ovarian functions. PMID- 1752600 TI - Possible contribution of prolactin in the process of ovulation and oocyte maturation. AB - The present study was undertaken to evaluate the effects of PRL in the process of ovulation and oocyte maturation. In the first experiment, using an in vitro perfused rabbit ovary model, the addition of PRL to the perfusate inhibited hCG induced ovulation in a dose-related fashion, without any reduction in progesterone synthesis. In a subsequent experiment, PRL directly inhibited both the degeneration and decomposition of surface epithelial cells and the disruption of connective tissue at the apex of the follicle wall. Furthermore, PRL inhibited hCG-stimulated plasminogen activator (PA) activity in mature follicles in a dose related fashion. In the final experiment, we demonstrated conditions in which rabbit oocytes matured in vitro acquire competence for early embryonic development. PRL, as well as gonadotropins and estradiol, was an important constituent in the process of oocyte maturation, promoting embryonic development. These results suggest that the preovulatory environment of PRL within the follicle may influence the process of ovulation and oocyte maturation. PMID- 1752601 TI - New aspects of prolactin in human reproductive physiology. Overview. PMID- 1752602 TI - Effects of prolactin on fertilization and cleavage of human oocytes. AB - The effects of PRL on fertilization and cleavage of human oocytes and subsequent pregnancy were studied. Forty-five patients (47 cycles) with euprolactinemic normal menstrual cycles undergoing in vitro fertilization (IVF) for the treatment of tubal infertility were selected for this study. The patients were divided into three groups dependent upon their mean serum PRL concentrations for the 3 days prior to oocyte retrieval; hypoprolactinemic (less than 10 micrograms/l), euprolactinemic (10-30 micrograms/l) and hyperprolactinemic cycles (greater than or equal to 30 micrograms/l). Multiple follicular development was induced with hMG, and 10 patients were randomized to receive bromocriptine beginning with the previous menstrual cycle. In the hypoprolactinemic cycle group, the fertilization rate was significantly lower than in the hyperprolactinemic cycle group, and the cleavage rate was significantly lower than in the other groups. The fertilization rates and the cleavage rates in the hyperprolactinemic cycle group were higher than those in the euprolactinemic cycle group; however, these differences were not statistically significant. While the pregnancy rates in the euprolactinemic cycle group were higher than in the other two groups, the numbers were too small for meaningful statistical comparison. The present study demonstrates that below normal concentrations of PRL have deleterious effects on IVF outcome. These data suggest that PRL may play a beneficial stimulatory role in oocyte maturation and the acquisition of developmental capacity. PMID- 1752603 TI - Effects of clomiphene citrate on serum hormone levels and endometrial thickness in an in vitro fertilization and embryo transfer program. AB - Hormonal alterations and pregnancy rates were compared between the clomiphene citrate (CC)-hMG combination cycle and the hMG cycle alone in an in vitro fertilization and embryo transfer program. In the CC-hMG cycle, the numbers of follicles developed, oocytes recovered and embryos transferred were higher than those in the hMG cycle (p less than 0.01, p less than 0.01 and p less than 0.05, respectively). Pregnancy rates of the CC-hMG cycle (6.7%/operation, 7.1%/embryo transfer), however, were lower than those of the hMG cycle (25%/operation, 31.6%/embryo transfer). PRL levels in the hMG cycle increased according to estradiol levels. In the CC-hMG cycle, CC might inhibit estradiol-induced hyperprolactinemia and the increase was lower even if the estradiol level was much higher than that of the hMG cycle until day 2. On day 4, the PRL level in the CC-hMG cycle further increased. The thickness of endometrium on day -2 in the hMG cycle alone was much thicker than that in the CC-hMG cycle (9.8 +/- 0.4 vs. 6.8 +/- 0.4 mm, mean +/- SEM). PMID- 1752604 TI - Effect of prolactin in serum and follicular fluid on fertilization and cleavage of human oocyte. AB - To assess the effect of PRL on fertilization and cleavage of oocytes, PRL levels in serum and follicular fluid of normoprolactinemic women who had undergone in vitro fertilization and embryo transfer (IVF-ET) were determined, and the relationship between PRL levels and fertilization and cleavage rates was studied. A transient increase in serum PRL at the ovulatory phase was found in about half of the IVF-ET patients during clomiphene stimulation, and increased levels of PRL in serum and follicular fluid at the ovulatory phase may suppress the fertilization and cleavage of oocytes. PMID- 1752605 TI - Renin- and angiotensin-like immunoactivities in human ovarian follicular fluid in in vitro fertilization. PMID- 1752606 TI - Effect of prolactin on the secretion of hypothalamic GnRH and pituitary gonadotropins. AB - In order to clarify the mechanism by which excess PRL inhibits gonadotropin release, in vivo and in vitro studies were performed with adult female rats. First, we examined the effect of hyperprolactinemia, produced by implantation of anterior pituitary glands under the kidney capsule, on catecholamine turnover in the medial basal hypothalamus (MBH) and on GnRH concentrations in MBH and hypophyseal portal blood. Rats bearing pituitary transplants exhibited increased turnovers of dopamine (DA) in the MBH, decreased concentrations of GnRH in the MBH and in plasma of hypophyseal portal blood and impaired gonadotropin release from the pituitary gland. Second, we examined the effects of PRL on DA release and of DA on GnRH release from rat hypothalamic cells. We observed that PRL stimulated [3H] DA release, and DA inhibited ionophore-induced GnRH release from dispersed hypothalamic cells. Third, we examined the effect of PRL on estrogen induced LH release using the in vitro perfusion system. We found that administration of PRL suppressed estrogen-induced LH release by suppressing GnRH release from the hypothalamus. These findings suggest that chronic hyperprolactinemia may increase dopaminergic tone in the MBH that may inhibit GnRH secretion from the MBH and LH release from the pituitary and that these processes may be responsible for disturbances of cyclic hypothalamic pituitary ovarian activity. PMID- 1752607 TI - Effects of prolactin on cultured human endometrial cells. AB - We report the effects of PRL on cultured human endometrial cells (epithelial cells and stromal cells) and discuss the role of PRL in implantation. Essentially similar responses to PRL in cell attachment and growth were obtained both in epithelial and stromal cells: a low concentration of PRL (3-30 ng/ml of PRL) enhanced cell attachment and growth. In contrast, the presence of a high concentration of PRL (over 100 ng/ml) resulted in a decrease in cell attachment and growth in normal culture conditions. Morphological analysis of epithelial glandular reformation on basement membrane extracts indicated that PRL had dual effects on endometrial epithelial cells: as a stimulator in low concentrations and an inhibitor in high concentrations. These data suggest that PRL may influence the functions of human endometrial cells in a dual way depending on its level and plays an important role in the implantation process. PMID- 1752608 TI - Heterogeneity of serum and amniotic fluid prolactin in humans. AB - The molecular heterogeneity of PRL was studied in serum and amniotic fluid using immunoperoxidase electrophoresis. In the amniotic fluid, larger molecular variants (greater than 117 kD), small PRL (20 and 23 kD) and cleaved PRL were present in the nonreduced condition. Newly, three mercaptoethanol (MCE)-resistant forms (76, 64 and 53 kD), and 25- and 23-kD forms appeared after treatment with MCE. Two variants, 64 and 23 kD, did not bind to concanavalin A (Con A), indicating a simple peptide without sugars. Other glycosylated forms, 76, 53 and 25 kD, bound to Con A. In maternal serum, the same components as those in the amniotic fluid were seen, except for a scanty amount of 23 kD and a newly appearing glycosylated variant of 28 kD in the reduced condition. This 23-kD form also appeared with the administration of TRH in women. PMID- 1752609 TI - Dimensions of potential arterial grafts for coronary artery bypass grafting in Indians--an autopsy evaluation study. AB - Total revascularization of the heart using as many arterial grafts as possible is the trend of the day. We have chosen two commonly used arterial grafts to evaluate their efficiency in myocardial revascularization in Indian subjects. An autopsy study was conducted in 25 cases. Both internal mammary arteries with their branches and the right gastroepiploic artery were harvested. These arteries were distended with heated Gelatin, deep frozen and their diameters were measured. In 56% of subjects diameter of internal mammary artery was 1.5 to 2.0 mm (n = 14). However 36% of subjects had diameter above 2.0 mm (n = 9). Musculo phrenic and superior epigastric arteries had 1.85 and 1.65 mm internal diameters respectively. The mean internal diameter of right gastro-epiploic artery was 2.3 mm. When these diameters were indexed to the body surface area, they were comparable with similar figures from western subjects. PMID- 1752610 TI - Effect of preload and heart rate manipulation on Doppler transmitral flow velocity pattern: search for load--independent parameters. AB - Pulsed Doppler transmitral flow-velocity provides a non-invasive method for serial evaluation of diastolic function. However confounding influence of loading conditions and heart rate on transmitral flow makes many conclusions suspect. To study the effect of preload, various parameters of Doppler mitral spectrum were studied in 11 patients with stable effort angina, angiographic coronary artery disease and intact global and segmental systolic function, before and after administration of sublingual isosorbide dinitrate (group 1). Following isosorbide dinitrate administration, there was a significant increase in heart rate (p less than 0.001), decrease in left ventricular end-diastolic volume (p less than 0.01), no change in left ventricular ejection fraction and systolic blood pressure. Peak E velocity, E velocity-time integral, E/A velocity time integrals ratio, acceleration and deceleration rates and diastolic filling period were significantly reduced whereas peak A velocity, A velocity time integral, acceleration and deceleration times and atrial filling period were unchanged. In 10 age-matched patients (group 2), atrial pacing performed to achieve similar degree of increase in heart rate as in group 1 (10 +/- 1 vs 12. +/- 4, p = NS), resulted in a decrease in E velocity time integral, E/A velocity time integrals ratio and diastolic filling period (p less than 0.01) without any significant change in any other parameter. Absolute A velocity time integral, acceleration and deceleration times are the only parameters of transmitral diastolic flow velocity profile which are relatively independent of preload and heart rate provided the change is small. PMID- 1752611 TI - Spectrum of tricuspid atresia--a study of 23 cases. AB - The present report describes the clinical and angio-cardiographic features of 23 cases of tricuspid atresia. Nineteen patients had type I anatomy, 2 patients had type II anatomy and 2 patients had type III anatomy. In addition to the standard features, there were some uncommon associations observed. These included double outlet right ventricle, double outlet left ventricle, single coronary artery, complete heart block, right axis deviation, ostium primum atrial septal defect and coarctation of the aorta. PMID- 1752612 TI - A pitfall of selective coronary angiography--dual anterior descending arteries in tetralogy of Fallot. PMID- 1752613 TI - Balloon mitral valvotomy in a patient with Ebstein's anomaly of tricuspid valve and rheumatic mitral stenosis. AB - We report a young woman with Ebstein's anomaly of tricuspid valve and rheumatic mitral stenosis who successfully underwent mitral valvotomy using double balloon technique. The clinical and haemodynamic benefits are sustained at 1 year followup. PMID- 1752614 TI - ST segment alternans during percutaneous transluminal coronary angioplasty. PMID- 1752615 TI - Pathology of aortocoronary saphenous vein graft. PMID- 1752616 TI - Recurrent stenosis after coronary angioplasty--current concepts and future direction. PMID- 1752617 TI - Role of foetal echocardiography in predicting perinatal outcome. AB - To establish foetal cardiovascular parameters as predictors of perinatal outcome in pregnancy, M-Mode, 2-D echocardiography and pulse Doppler study was performed at 24-32 weeks of gestation in 65 pregnancies. These pregnancies were followed up for perinatal outcome. The studied population included 24 normal pregnancies, 21 pregnant women with heart disease (14 rheumatic and 7 congenital heart disease) and 20 high risk pregnancies (bad obstetric history in 7, suspected intrauterine growth retardation in 4, hypertensive disease of pregnancy in 6 and diabetes mellitus in 3). There was no perinatal mortality. Two foetuses were born with complete heart block and one with a small ventricular septal defect; 6 neonates had intrauterine growth retardation and two of these had neonatal asphyxia with APGAR score less than 6 at one minute. Anatomically normal heart was correctly diagnosed in all 64 foetuses and ventricular septal defect was detected antenatally in one. Antenatal diagnosis of complete heart block was correctly made in two foetuses. One new born with complete heart block required a permanent pacemaker, which was implanted. The ratio of peak velocity across mitral valve during atrial systole (A) to peak velocity during early diastolic ventricular filling (E) was chosen to correlate with perinatal outcome. The ratio was less than 1.0 in 6 foetuses, all of whom were subsequently confirmed to have intrauterine growth retardation. In normal pregnancies A/E ratio was more than 1.0. We conclude that foetal echocardiography is a useful tool for predicting perinatal outcome and may be helpful in screening patients who require specific perinatal management. PMID- 1752618 TI - Utility of foetal echocardiography in clinical practice. PMID- 1752619 TI - Electrocardiographic features of atrial depolarization during pacing of right atrial appendage. AB - Identification of atrial capture during pacing from right atrial appendage is frequently difficult. Electrocardiograms of forty five patients implanted with AAI/DDD pacemakers (thirty unipolar, fifteen bipolar) were analysed to characterize the specific morphology of paced P waves. Compared to sinus P waves, atrial pacing resulted in atrial depolarization of lower amplitude (0.16 +/- 0.05 mv vs 0.11 +/- 0.032 mv, P less than 0.005) but increased duration (0.07 +/- 0.009 sec vs 0.08 +/- 0.017 sec, P less than 0.005). P wave morphology was similar in unipolar and bipolar pacing units. It was positive in lead I (80%), II (71.11%), III (80%) and aVF (75.55%). In lead aVL, paced P waves were usually diphasic with an initial negative deflection (35.55%). Precordial leads showed paced atrial depolarization of small amplitude and did not help in identification of atrial capture. In unipolar pacing P waves were best seen in lead III because of small pacing spike in this lead. Lead II was suitable for identification of paced P waves in bipolar pacing. Thus careful examination of standard ECG leads for paced P waves of low amplitude, prolonged duration and specific morphology can help in confirming atrial capture following pacing stimulus from right atrial appendage. PMID- 1752620 TI - Percutaneous transluminal coronary angioplasty of distal lesions: comparison of results with proximal lesions. AB - The results of percutaneous transluminal coronary angioplasty (PTCA) of 57 distal lesions were compared with 55 proximal lesions in 42 patients, aged 31 to 66 years (mean +/- SD: 51 +/- 9 yrs). Twenty nine (69%) had multivessel and 13 (31%) single vessel disease. The lesions classified as distal were located in left anterior descending (LAD) artery beyond the origin of second diagonal (D2), left circumflex (LCx) after the main obtuse marginal (OM) and right coronary artery (RCA) after the origin of acute marginal branch. Also included in this category were lesions in the second diagonal and obtuse marginal branches, two centimeters from their origin and stenosis in the posterior descending and posterolateral left ventricular branches of RCA. Out of 57 distal lesions 18 were 'complex' because of tandem location (5 patients), ulceration (6 lesions) and intraluminal thrombi (2 lesions). There was no significant difference in the mean luminal diameter stenosis between distal and proximal lesions, before and after PTCA. The primary success rate of angioplasty was 89.5% for the distal and 94.5% for the proximal lesions (P = NS). Inability to position the balloon across the lesion accounted for more failures in distal (3) compared to proximal (1) location. There were no major complications. Our results show that PTCA of distal lesions can be performed with a high rate of success, which is comparable to those with classical proximal lesions in the same patients. PMID- 1752621 TI - Safety and predictive value of exercise stress testing within three days after percutaneous transluminal coronary angioplasty. AB - The safety and efficacy of exercise stress testing within three days of successful coronary angioplasty was evaluated in 226 patients with coronary artery disease; 137 patients had single-vessel disease (SVD) and 89 had multi vessel disease (MVD). Comparisons were made between patients with SVD and MVD and between patients whose vessels restenosed and those whose vessels remained patent. The post-angioplasty exercise test was positive in 48% of SVD and 49% of MVD patients. However, a positive result did not predict future restenosis. There was a significantly [p = 0.004] higher proportion of patients in the MVD group, compared with the SVD group, who exhibited greater than or equal to 2mm ST depression, but again this was not indicative of restenosis. No complications as a direct result of having an early exercise test occurred. Exercise stress testing proved safe and was effective in demonstrating relief from angina in most patients early after coronary angioplasty. It did not, however, predict restenosis. PMID- 1752622 TI - Acute myocardial infarction in north Kerala--a 20 year hospital based study. AB - This is a retrospective study of patients with first attack of myocardial infarction admitted to Medical College Hospital, Calicut during the years 1969 to 1988. The data analysed were compared to other hospital based studies in India and abroad. A striking increase in the percentage of acute myocardial infarction was observed. There was also an increase in the occurrence of myocardial infarction in the young. A properly designed population based study is warranted. PMID- 1752623 TI - Assessment of antianginal efficacy of long-acting sustained release isosorbide dinitrate in comparison with short-acting isosorbide dinitrate. AB - A quadruple blind randomized cross-over study evaluated the therapeutic efficacy of twice a day long acting sustained release isosorbide dinitrate (SRISDN) in comparison with 4 times daily of the short acting isosorbide dinitrate in 18 patients with stable angina pectoris (NYHA class II-III) with a positive exercise treadmill test. The antianginal effect of sustained release isosorbide dinitrate (SRISDN) (exercise duration 472.61 +/- 112.49 sec and anginal episodes per week (1.33 +/- 1.18) was not significantly different (p less than 0.05) when compared to conventional isosorbide dinitrate (exercise duration 468.33 +/- 135.28 sec and anginal episodes per week 1.55 +/- 104). Twice a day long acting sustained release isosorbide dinitrate is as effective as four times a day conventional short acting isosorbide dinitrate. Such a regimen is likely to lead to a better patient compliance and ease of antianginal therapy. PMID- 1752624 TI - Polyene antibiotics in the membrane environment. AB - The cytotoxic activity of the polyene antibiotics mainly depends on the appearance of the drug species which arises from drug-sterol complexation. The unsaturation and intact macrolide ring of the polyenes are the requirements for the biological activity. All the polyene antibiotics can form the complex with the sterol having 3 beta-OH group, and planar ring and a hydrophobic side chain. Aromatic polyene antibiotics with positively charged head group have been considered as most potential antifungal agents. PMID- 1752625 TI - Cloned single copy DNA sequences of Mycobacterium tuberculosis as DNA probes. AB - A recombinant genomic clone was isolated from a lambda gt 11 library of M. tuberculosis on the basis of lack of hybridization with M. avium and M. kansasi. The specificity and sensitivity of M. tb DNA probes, 2.5 and 2.3 kb in size, were assessed by Southern blot and dot blot hybridization. These did not cross hybridize to DNA of mycobacteria other than members of M. tb complex, nor with DNA of non mycobacterial origin. Sensitivity was determined to be 200 pg which is equivalent to 10(4) bacilli. Genomic Southern hybridization indicated single copy nature of the probes. PMID- 1752626 TI - Binding of Cu(2+)-beta-cyclodextrin complex to calf thymus DNA. AB - Cu(2+)-beta-cyclodextrin (1:1) complex has been found by UV, fluorescence and CD spectroscopy, polarimetry and gel electrophoresis to bind reversibly to calf thymus DNA. Using UV the binding constant was found to be 45280 +/- 7100 M-1. The binding of the complex Cu(2+)-BCD with DNA was stronger than that of free Cu2+. However the ternary complex formed thus was destroyed by EDTA. PMID- 1752627 TI - Isolation and characterization of a naturally occurring inhibitor from mung bean (Vigna radiata) seedlings for serine hydroxymethyltransferase. AB - A naturally occurring inhibitor of serine hydroxymethyltransferase (EC 2.1.2.1) in mung bean seedlings extracts was purified by ammonium sulphate precipitation, phenyl-Sepharose chromatography followed by heating to release the inhibitor bound to the protein. The inhibitor had an absorption maximum at 200 nm, was not precipitated by trichloroacetic acid, was dialysable and resistant to inactivation by heating at 98 degrees C for 4 hr, protease and ribonuclease digestion; but was acid labile. The chromatographically pure preparation inhibited both mung bean and sheep liver SHMT. Qualitative and quantitative analyses indicated that it contained a carbohydrate moiety, an O-amino and vicinal diol groups. Paper electrophoresis at pH 4.3 suggested that the inhibitor was positively charged. PMID- 1752628 TI - Differential binding of NAD+ to acyl glyceraldehyde-3-phosphate dehydrogenase and its role in the acyl group transfer reaction. AB - Enzyme protein fluorescence of di-furylacryloyl-glyceraldehyde-3-phosphate dehydrogenase (di-FA-GPDH:lambda max.excitation 290 nm, lambda max.emission 338 nm) is quenched about 28% on saturation with NAD+. Results of fluorometric titration of di-FA-GPDH with NAD+ suggest the presence of two tight and two loose coenzyme binding sites (Kdiss. 0.1 and 6.0 microM, respectively). Initial rates of the NAD(+)-dependent reaction of di-FA-GPDH with arsenate and phosphate and of mono-FA-GPDH with phosphate have been determined at varying coenzyme concentrations. The data suggest that binding of NAD+ at the tight sites does not activate the acyl group for its reaction with the acceptor (phosphate or arsenate). The group transfer reaction is dependent only on NAD+ binding to the loose sites, which carry the acyl group. The large difference in the NAD+ binding affinity to the two types of sites and their different effects on the group transfer reaction impart a sigmoidal shape to the rate versus [NAD+] plots. The sigmoidicity is abolished if the reactive SH groups at the unacylated sites are blocked by carboxymethylation. PMID- 1752629 TI - Protein adsorption at solid-liquid interfaces: Part IV--Effects of different solid-liquid systems and various neutral salts. AB - Adsorption isotherms of BSA at the solid-water interfaces have been studied as a function of protein concentration, ionic strength of the medium, pH and temperature using silica, barium sulphate, carbon, alumina, chromium, ion exchange resins and sephadex as solid interfaces. In most cases, isotherms for adsorption of BSA attained the state of adsorption saturation. In the presence of barium sulphate, carbon and alumina, two types in the isotherms are observed. Adsorption of BSA is affected by change in pH, ionic strength and temperature of the medium. In the presence of metallic chromium, adsorbed BSA molecules are either denatured or negatively adsorbed at the metallic interface. Due to the presence of pores in ion-exchange resins, adsorption of BSA is followed by preferential hydration on resin surfaces in some cases. Sometimes two steps of isotherms are also observed during adsorption of BSA on the solid resins in chloride form. Adsorption of BSA, beta-lactoglobulin, gelatin, myosin and lysozyme is negative on Sephadex surface due to the excess adsorption of water by Sephadex. The negative adsorption is significantly affected in the presence of CaCl2, KSCN, LiCl, Na2SO4, NaI, KCl and urea. The values of absolute amounts of water and protein, simultaneously adsorbed on the surface of different solids, have been evaluated in some cases on critical thermodynamic analysis. The standard free energies (delta G0) of excess positive and negative adsorption of the protein per square meter at the state of monolayer saturation have been calculated using proposed universal scale of thermodynamics. The free energy of adsorption with reference to this state is shown to be strictly comparable to each other. The magnitude of standard free energy of transfer (delta G0B) of one mole of protein or a protein mixture at any type of physiochemical condition and at any type of surface is observed to be 38.5 kJ/mole. PMID- 1752630 TI - Characterization of mitochondrial membrane fragments resulting from spontaneous swelling: novel stimulation of NADH-dependent respiration by carboxylic acids. AB - Metabolically induced high amplitude swelling of rat liver mitochondria has been found to result in the formation of a heterogeneous population of mitochondrial membranes consisting of right side-out particles with occluded fumarase activity and inside-out particles/fragments capable of NADH-dependent respiration. This rotenone-sensitive, uncoupler-insensitive, NADH-dependent respiration was specifically and instantaneously stimulated by several ligands such as glutamate and malate (which can be metabolized) and, interestingly, even lactate (which could not be metabolized by the swollen mitochondria). These observations suggest that high amplitude swelling results in a novel type of control of respiration in these fragments. PMID- 1752631 TI - NADH-dependent respiration in osmotically inactive swollen mitochondria: does transport replace phosphorylation in mediating respiratory control in swollen mitochondria? AB - Rotenone-sensitive, uncoupler-insensitive, NADH-dependent respiration was demonstrated in osmotically inactive fragments of the mitochondrial inner membrane obtained following high amplitude (spontaneous) swelling. This NADH dependent respiration as well as mitochondrial ATPase activity was stimulated by ligands which are known to be transported by specific transporters/mechanisms. The ligands capable of this anomalous respiratory control included several intermediates of the citric acid cycle, besides non-metabolizable ligands including lactate, cations such as K+ and Ca2+. The interaction between NADH dependent respiration and these ligands, as manifested by stimulation of respiration, was strongly ionic strength-dependent. The thermodynamic relationship between respiratory control and stimulation of transport ATPase by the relevant transportable ligands could also be demonstrated in the conventional (rat liver) microsomes. These experimental results offer a novel experimental base for search into an intra-membranous mechanism of energy transduction. PMID- 1752632 TI - Hepatic plasma membrane fluidity and dietary proteins. AB - Effect of protein deficient diet on hepatic plasma membrane fluidity has been studied in rats using (i) steady state fluorescence polarization and anisotropy, (ii) phospholipid and cholesterol contents, (iii) phospholipid fatty acid composition, (iv) turnover of phosphatidyl choline (PC), and (v) activities of membrane-bound enzymes as parameters and rats fed casein (20%) diet as standard group. A significant increase in steady state fluorescence and anisotropy values was registered in the deficient group, indicating increased resistance and hence decrease in fluidity of the plasma membrane. Supplementation of the diet with lysine and threonine improved these values, thereby suggesting the significance of diet for membrane fluidity. Simultaneous significant alterations in other parameters, viz. (i) decrease in PC, PE and free cholesterol and increase in esterified cholesterol contents, (ii) decrease in unsaturation of fatty acids of PC, (iii) decrease in incorporation of NaH2 32PO4, [CH3-14C]choline and [CH3 14C]methionine into plasma membrane PC, and (iv) decrease in activities of plasma membrane 5'-nucleotidase and phosphodiesterase along with increase of (Na(+) K+)ATPase and adenyl cyclase, were observed in the deficient group which on supplementation with lysine and threonine showed improvement over alterations. PMID- 1752633 TI - Covalently bound fatty acids in the gastrointestinal epithelial cell membrane. AB - Myristic, palmitic, stearic, oleic and linoleic acids have been identified as the covalently bound fatty acids in the monkey gastrointestinal mucosal membrane proteins and among them palmitolation was predominant. Distribution studies in various regions of the gastrointestinal mucosa showed no significant difference in the content and composition of covalently bound fatty acids in these membrane and most of the fatty acids were found to be ester linked. Total membranes from isolated crypt and villus enterocytes and colonocytes had similar composition of these fatty acids. Covalently bound fatty acid levels were higher in the small intestinal brush border membrane. As suggested for the mucus glycoproteins, covalently bound fatty acids in the intestinal epithelial cell membrane may protect these membranes from proteolytic damage from the luminal proteases. PMID- 1752634 TI - Evaluation of media for primary isolation of Campylobacter jejuni from faecal samples from children and animals. AB - Different media were used for primary isolation of Campylobacter. Butzler & Preston medium was found to be more selective compared to Skirows & Blaserwang. PMID- 1752635 TI - Enzyme linked immunosorbent assay (ELISA) for detection of meningococcal antibodies in north India. AB - Serological response was studied in 16-30 years high risk age group, during the period December 1986-April, 1988, following meningococcal vaccine (Biomerieux, France). A total of 200 serum samples were collected from 50 individuals before vaccination and at 3 intervals of 1, 3 and 6 months post-vaccination respectively. Antibody response was measured by Enzyme Linked Immuno-Sorbent Assay (ELISA) and indirect haemagglutination assay (IHA). In the vaccinees antibody response by IHA test showed 56%, 82%, 78% and 74% positivity in the pre vaccination, 1 month, 3 months and 6 months post vaccination samples. By ELISA 2%, 80%, 74% and 66% of the above groups showed serological response. Difference in the pre-vaccination and titres/O.D. of various post-vaccination groups was found to be statistically significant (p less than 0.001). There was, however, no significant difference (p greater than 0.05) amongst the titres/O.D. of three post-vaccination groups. Similarly acute and convalescent blood samples of 25 patients and one sample each of 31 contacts was studied for antibody response. In general, higher antibody titres are produced with systemic infection than with local nasopharyngeal infection or following vaccination. PMID- 1752636 TI - The bicuspid aortic valve--an autopsy study. AB - Congenital Bicuspid Aortic Valve is a common congenital anomaly. We studied 48 cases of bicuspid aortic valve seen over a period of 20 years. 18 cases were associated with other congenital anomalies, patent ductus arteriosus being the most frequent. 30 were isolated lesions. The morphology of the cusps and position of raphe were noted. Calcification and infective endocarditis were frequently noted in the isolated forms of Bicuspid Aortic Valve. Coronary arteries were dissected in 32 cases to determine the dominance. PMID- 1752637 TI - Actinomadura madurae causing mycetomas in Madras. AB - Two hundred and ten histologically diagnosed cases of mycetoma filed in the Departments of Pathology of four Medical Colleges in Tamil Nadu, India, between 1964-1987 were subjected to detailed histopathological study; Actinomadura madurae, was found in 73 of them. In nine cases of mycetoma pedis, the organism A. madurae has been isolated in pure culture. In one case, the lesions were present in both the feet. The characteristic cream-coloured granules were seen in all. The lesions responded well to a combination of Streptomycin and dapsone. PMID- 1752638 TI - Diagnostic and prognostic significance of serum cholinesterase and lactate dehydrogenase in breast cancer. AB - Serum cholinesterase (ChE) and Lactate dehydrogenase (LDH) activities were estimated in 40 cases of carcinoma breast, 25 cases of benign tumours and compared with healthy controls (30 cases). Significant difference in enzyme activities were obtained between benign and malignant neoplasms of the breast when compared with each other as well as when compared with healthy controls. Also, there were significant enzyme changes between non-metastatic cases and those with metastasis and when Stage I and Stage II cancers were compared with those in Stage III and Stage IV. No difference in enzyme levels were recorded between pre and post-operative cases and in different types of breast cancers. While ChE was depressed in 80 per cent cases of malignancy breast, serum LDH was raised in 73.3 per cent cases. PMID- 1752639 TI - Determination of the probable date of delivery using vaginal cytology as an index. AB - 70 normal pregnant females were used for the study, 47 of whom had vaginal cytological follow-up from week 32 till the first stage of labour. 23 additional patients had vaginal smears made in the first stage of labour. The combined intermediate cell value was used as an index of impending labour with values at week 38 being 90.35 +/- 0.0863, week 39 being 89.41 +/- 0.1934, week 40 being 81.25 +/- 0.0558 and at labour being 78.75 +/- 0.0995. The primigravidae showed a stepwise, gradual decrease in mean intermediate cell value from week 38 onwards, while the multigravidae showed a drop only at week 40. From this study, it has been shown, that it is possible to predict labour. It was also evident that there is a difference in reactivity of a primigravida versus multigravida to decreases in circulating progesterone as gauged by intermediate cell counts. PMID- 1752640 TI - Evaluation of cryostat frozen section in the diagnosis of surgical biopsies. AB - Cryostat frozen section technique was used on 1300 surgical biopsies. On final paraffin sections diagnosis there were 270 benign neoplasms, 200 malignant neoplasms and 830 inflammatory and non-neoplastic lesions. The overall accuracy using frozen section was 98.48 per cent with one false positive result (0.07 per cent), 17 false negative results (1.3 per cent) and 2 deferred diagnosis (0.15 per cent). PMID- 1752641 TI - Perfusion nephropathy--a rare histological entity mimicking "hyperacute rejection". PMID- 1752642 TI - Malignant lymphoma scalp--a case report. PMID- 1752643 TI - Arcanobacterium haemolyticum brain abscess in a child (a case report). PMID- 1752644 TI - Histoplasmosis simulating cutaneous carcinoma. PMID- 1752645 TI - Autologous bone marrow transplantation. PMID- 1752646 TI - Bacteriology of diabetic foot ulcers. AB - Seventy five diabetic foot ulcers were cultured using optimal aerobic and anaerobic microbiologic techniques. There were a total of 223 isolates (162 aerobes and 61 anaerobes) representing an average of 2.97 bacterial species per specimen. Mixed organisms were the most common isolates. Staphylococcus aureus was the commonest isolate being recovered in 60% of cases. Anaerobic organisms were isolated in 46 patients (61.33%) and the most frequent anaerobe isolated was Bacteroides fragilis. The other organisms predominantly isolated were Proteus, Klebsiella, Pseudomonas, Peptoccus and Clostridia. Antibiogram showed discouraging pattern with commonly used antibiotics. Metronidazole and gentamicin were the most effective antimicrobial agents against anaerobic and aerobic organisms respectively. Appreciation of the causative organisms in diabetic foot and their antibiotic sensitivity is essential for institution of appropriate antibiotic therapy. PMID- 1752647 TI - T and B lymphocytes in patients with enteric fever. AB - Estimation of T and B lymphocytes was done in 50 patients of enteric fever, 50 duration matched non enteric fever patients and 50 normal healthy individuals. The difference in both early and late rosette forming T lymphocytes was found to be statistically significant in enteric versus non-enteric patients. Significant difference was also observed in enteric versus normal individuals in case of late rosette forming T lymphocytes. PMID- 1752648 TI - Circulating immune complexes and complement in bancroftian filariasis. AB - Sixty filarial cases, 30 endemic normal individuals and 10 non endemic subjects were investigated for the presence of Circulating Immune Complexes (CICs) and Complement Component C3. Using Polyethylene Glycol precipitation and Polyethylene Glycol precipitation-Complement Consumption methods, it was observed that CICs were raised significantly in chronic lymphatic filariasis and Tropical Pulmonary Eosinophilia (TPE) groups. The results observed by both the techniques for detection of CICs were comparable. Low levels of C3 were detected in chronic lymphatic filariasis cases by single radial immunodiffusion method, suggesting the utilization of complement by immune complexes. PMID- 1752649 TI - Cell marker studies in undifferentiated soft tissue sarcoma. AB - 100 cases of undifferentiated soft tissue sarcomas were studied using cell markers by immunoperoxidase technique with DAB as substrate. Vimentin, Desmin, Myoglobin, Actin, Keratin, Epithelial Membrane Antigen, S-100 protein, F VIII R Ag, A1 Antitrypsin, A1 Antichymotrypsin, Collagen-IV and UEA-1 lectin were used as markers. Fibrosarcoma was consistently positive for Vimentin and Collagen-IV. The undifferentiated Rhabdomyosarcoma showed strong and consistent positivity for Vimentin Actin and Myoglobin. Desmin positivity was the hallmark of leiomyosarcoma, whereas the malignant schwannomas were identified by their S-100 positivity. This marker along with A1AT and A1ACT reactivity was of great use in the identification of malignant fibrous histiocytoma. Angiosarcoma/malignant haemangioendothelioma could be identified with great accuracy by their strong positivity for F VIII RAg and UEA-1 lectin. Other miscellaneous sarcomas also could be identified by their specific reactivity to the markers used. We consider immunohistochemistry to be an important and essential adjunct to routine stains in the diagnosis of undifferentiated soft tissue sarcomas. PMID- 1752650 TI - The challenge of multi-drug resistant typhoid fever. PMID- 1752651 TI - Current concepts of epidemiology, diagnosis and treatment of childhood tuberculosis in the United States. PMID- 1752652 TI - Multi drug resistant Salmonella typhi infection: clinical profile and therapy. AB - Multiple drug resistant Salmonella typhi infection was observed in thirty five recent cases among forty eight children with bacteriologically proven enteric fever. Incidence of complications such as shock, myocarditis, encephalopathy and paralytic ileus was higher among these. A combination of cephalexin and gentamicin was successfully used in the management of these children. PMID- 1752653 TI - Maternal fetal immunological relationship particularly mycobacterial immunity. AB - Thirty-nine paired maternal and cord blood from normal full term deliveries were tested for lymphocyte function by proliferative response to mitogens Phytohemagglutinin-P (PHA) and Poke week mitogens (PWM). Monocyte function was assessed by the ability of the monocytes to release hydrogen peroxide (H2O2) in response to standard stimulus (PMA). Mycobacterial immunity was assessed by lymphocyte proliferative response to purified proteins derivative (PPD) and IgM and IgG antibody response to H37Rv and 5 atypical mycobacteria. Lymphocyte functions were significantly lower in cord blood (PHA 20.6, PWM 21.2) as compared with maternal blood (PHA 65.8, PWM 37.8). The capacity of fetal monocytes to release H2O2 was comparable to maternal monocytes. The mean proliferative response of fetal lymphocytes to tubercular protein (PPD) was 0.67 as compared (P less than 0.01) to maternal lymphocytes (3.79). Nearly 86% of the cord blood did not show any response to PPD. None of the cord blood showed IgM antibody response to H37Rv nor to any of the range of 5 atypical mycobacteria though maternal IgM and IgG response was present. There was only passive transfer of IgG antibody from mother to fetus. Hence, though this is a highly endemic area for atypical mycobacteria and M. tuberculosis, there was apparently no transplacental transfer of antigen in normal sensitized mothers. PMID- 1752654 TI - Cerebrospinal dehydrogenases in central nervous system infections. AB - Cerebrospinal fluid (CSF) dehydrogenases were studied in 42 controls, 23 children with pyogenic meningitis, 22 with tuberculous meningitis and 19 with encephalitis to assess their usefulness in differentiating between the different central nervous system infections. CSF-LDH and ICD activity was increased in CNS infections (p less than 0.0001), LDH being significantly higher (p less than 0.001) in pyogenic meningitis than in tuberculous meningitis or encephalitis. However, ICD activity was significantly different in each of these conditions (p less than 0.001). The dehydrogenase activity declined with subsequent clinical improvement, in all children with meningitis. A significant direct relationship was found between the enzyme activity and CSF protein content as well as total cell count. The 95% confidence interval confirms the utility of assaying CSF dehydrogenase activity to differentiate various CNS infections, thus improving the diagnostic ability. PMID- 1752655 TI - Enuresis: analysis of 100 cases. AB - One hundred children with enuresis were studied to find out various factors responsible for this condition. Enuresis was more frequent in first born, service class and bottle fed children. There was a significant role of stress factors in causation of enuresis. We found a higher frequency of behavioral symptoms among children with enuresis. There was no significant correlation between enuresis and sex, education of parents, social class, sleep patterns, age of mother at marriage and intellectual grades of the children. Worm infestations, giardiasis, amebiasis and urinary infection were seen in 70% of cases. General body weakness, cold and nervousness were the common causes of enuresis in the parents' opinion. The main reason for not seeking the treatment at an early stage in view of parents' was that they thought enuresis a normal variant. PMID- 1752656 TI - Diagnostic and therapeutic colonoscopy in children: experience from a pediatric gastroenterology centre in India. AB - Eighty colonoscopies were performed in 72 children suffering from various colonic disorders. The indications for colonoscopic examination were bleeding per rectum (83.3%), prolonged colitis (14.0%) and colonic obstruction (2.7%). Total bowel wash with normal saline was very good for colonic preparation in majority of the cases. Pediatric colonoscope (PCF-Olympus) was used and the procedure performed under sedation with intravenous diazepam and pentazocine. Juvenile polyps were the commonest lesions (69.4%). Diagnosis of idiopathic ulcerative colitis, acute colitis, tuberculous colitis, amebic colitis and allergic colitis was made in 5.5, 4.2, 2.7, 1.3 and 1.3% cases, respectively. Tuberculous hypertrophic lesion and tuberculous stricture was seen in one case each. The commonest site of juvenile polyps was rectosigmoid region. Ninety per cent of them were single, 8% had polyps ranging from 2-4 in number and one (2%) child had juvenile polyposis coli. Successful colonoscopic removal of polyps with polypectomy snare was possible in 96% cases. No complications were observed. Colonoscopy is a safe and useful mode of investigation of colonic disorders in expert hands. It has a great therapeutic value in childhood. PMID- 1752657 TI - Calcium, magnesium and phosphorus concentrations in human milk and in sera of nursing mothers and their infants during 26 weeks of lactation. AB - Longitudinal calcium, magnesium and phosphorus concentrations were measured in milk and sera of 20 nursing mothers and their infants during a period of 26 weeks. Within this period, progressive increase in serum calcium, magnesium and total protein concentrations were observed in breast-fed infants, in association with decreasing phosphorus content of breastmilk. Maternal serum calcium, magnesium and total protein concentrations also increased during this period. It is speculated that a decrease in serum phosphorus in breast-fed infants can cause rickets. It is also speculated that the physiological rise in serum calcium concentrations in maternal serum may be related to the physiological increase in serum total protein. PMID- 1752658 TI - Periventricular hemorrhage in term newborns originating from germinal matrix. AB - Six term newborns, presenting with seizures, in whom cranial sonogram showed isolated periventricular hemorrhage (SEH) are described. Age of onset of seizures ranged from day one of birth to day twenty-one. Seizures appeared spontaneously in previously healthy newborns in three cases. All but one survived, and three have near normal development. Isolation of hemorrhage to the periventricular area suggests germinal matrix to be the source of hemorrhage in these cases. These cases also emphasize the need to consider diagnosis of IVH in term-newborns presenting with seizures. PMID- 1752659 TI - Tuberculosis of petrous apex. PMID- 1752660 TI - Immunoglobulin profile in tuberculous and pyogenic meningitis. PMID- 1752661 TI - Hemoptysis in tetralogy of Fallot. PMID- 1752662 TI - Dental caries in children. PMID- 1752663 TI - Ciprofloxacin in the management of multiple drug resistant typhoid fever. PMID- 1752664 TI - Erythroleukemia. PMID- 1752665 TI - Hypokalemic paralysis. PMID- 1752666 TI - Chloramphenicol resistant typhoid fever. PMID- 1752667 TI - Treatment of enteric fever--what next? PMID- 1752668 TI - Non-nutritive sucking in pre-term infants on the full breast. PMID- 1752669 TI - Why dilute feeds? PMID- 1752670 TI - Rapid epidemiologic assessment. PMID- 1752671 TI - Quantitation of proteinuria using protein-creatinine ratio in random urine samples. AB - Estimation of proteinuria in children is cumbersome when a 24 h urine collection is needed. In the presence of a stable glomerular filtration rate, the ratio of urinary protein and creatinine should reflect the protein excretion. One hundred samples of urine (24 h and random samples) were collected from 50 children with nephrotic syndrome, 25 with nephrotic syndrome in remission and 25 normal children. The 24 h urine total protein and random urine protein-creatinine ratio were assessed on these samples. Linear regression analysis of the results showed excellent correlation between the values (r = 0.81, p less than 0.001). A random urine protein-creatinine ratio of greater than 3.5 correlated with massive proteinuria, while a ratio less than 0.2 was suggestive of physiological values. The sensitivity, specificity, positive and negative predictive values of the protein-creatinine ratio in massive proteinuria were very high. We conclude that the random urine protein-creatinine ratio can be used reliably to assess the degree of proteinuria in children. PMID- 1752672 TI - Evaluation of naked eye single tube red cell osmotic fragility test in detecting beta-thalassemia trait. AB - The Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) was applied to 4 groups of subjects: (i) Normal; (ii) Proven beta-thalassemia trait carriers; (iii) Iron deficiency anemia; and (iv) other hemoglobinopathies, to evaluate its effectiveness as a screening test for beta-thalassemia minor. The test was successful in detecting 105/110 subjects with beta-thalassemia trait. The sensitivity of the test was 95.5% and specificity was 87%. The predictive value of the positive test was 70.5% and that of the negative test was 98.3%. NESTROFT was also positive in 9/17 subjects with HbS trait, in 3/3 subjects with HbD trait and in 1/1 subjects with HbE trait. The test proved to be simple, cheap, easy to perform and adaptable for field surveys, coming close to an ideal screening test for beta-thalassemia minor. PMID- 1752673 TI - Icterometer: a useful screening tool for neonatal jaundice. AB - One hundred and sixty one jaundiced newborns were investigated for the usefulness of perspex icterometer as a screening tool for neonatal jaundice. Along with serum bilirubin estimation, icterometer score was simultaneously obtained in all the cases. The correlation between serum bilirubin and icterometer score was high (r = 0.99). The icterometer was useful in various subgroups. A high sensitivity, specificity, positive and negative predictive value was seen in all the groups. A possible role of icterometer in India for screening newborns with jaundice at peripheral level is highlighted. PMID- 1752674 TI - Reduction in parenteral nutrition related complications in the newborn. AB - A comparison of total parenteral nutrition (TPN) related complication in newborns was made between two study periods, namely, 1986 (Study A) and 1989-90 (Study B). A significant reduction was seen in all complications in Study B. Local complications (thrombophlebitis, gangrene, abscess) reduced from 80.0 to 29.4%, septicemia from 52.0 to 11.7% and metabolic complications from a computed mean of 1.6 episode per baby to 0.88 episode per baby. The reduction in these complications has been attributed to the following additional inputs in the recent study (i) Additional staff (research officers, nurses, biochemist); (ii) Better training of resident staff; (iii) Use of a laminar flow system for mixing solutions; (iv) Specially designed locally manufactured intravenous sets and accessories; and (v) Use of well balanced nutrient solutions. Outstanding problems perceived are--high incidence of TPN-related cholestasis (14.7%), azotemia (26.4%), central catheter-related sepsis (75.0%) and the falling, but yet high cost of the technique (Rs. 650 per day). PMID- 1752675 TI - Clinical profile of severe birth asphyxia. AB - In this retrospective analysis, 56 babies with Apgar score 3 and less were studied. In 33, successful bag-mask ventilation was carried out. Seventeen babies received endotracheal IPPV. In 9 out of them bag-mask ventilation was never tried whereas in 8 bag-mask ventilation had failed. In 6 babies physical stimulation and blast of oxygen on the face was adequate. Following this experience, in the subsequent years, endotracheal intubation was required mainly in extremely low birth weight babies or babies with Apgar score 0 at birth. During the study period, drugs were used in about 50% babies. In subsequent years this figure has come down to 10%, that too in special situations. This study helped us to evolve a policy in resuscitations severely asphyxiated babies. Bag-mask ventilation is the first choice. Failure to achieve progressively improving Apgar score by 1 minute, usually 4-5, is an indication for endotracheal intubation. Drugs are required in special situations only. PMID- 1752676 TI - Evaluation of ceruloplasmin in neonatal septicemia. AB - Serial serum ceruloplasmin (Cp) levels were estimated in healthy and septicemic neonates, using single radial immunodiffusion. In 25 healthy neonates mean Cp levels were 19.82 mg/dl at birth, 18.20 mg/dl at 12-24 hours, 17.26 mg/dl at 14 +/- 4 days and 17.68 mg/dl at 28 +/- 4 days of life. For the entire neonatal period the mean Cp levels were computed to be 18.24 mg/dl. In 20 culture positive, septicemic neonates, mean Cp levels were 27 mg/dl at onset of disease, 28.65 mg/dl 12-24 hours later and 36.2 mg/dl after 7 +/- 3 days of start of illness (p less than 0.001 for all sampling intervals as compared to healthy group values in first month of life). The mean Cp levels were unaffected by gestational age in both groups. In the septicemic neonates, the mean Cp levels in dying neonates did not differ significantly from recovering neonates for all sampling intervals. It is concluded that estimation of serum Cp levels may help in diagnosis of neonatal septicemia, but it is not useful as an early diagnostic aid or for prognostication. PMID- 1752677 TI - Congenital diaphragmatic hernia: a retrospective autopsy study. AB - Congenital diaphragmatic hernia is one of the acute pediatric surgical emergencies and an important cause of perinatal mortality. Its incidence varies from 1 in 2000 to 1 in 5000 live-births, with a greater incidence in stillbirths and abortions. Non-operative mortality is generally reported as 100% and early diagnosis is imperative. A retrospective study of all infant and neonatal autopsies done during last 30 years (1960 to 1989) was conducted. Ten cases of congenital diaphragmatic hernia were encountered among 588 autopsies and its incidence was 1.7% of all infant and neonatal autopsies, dying due to varying causes. The male:female ratio was 7:3, while maternal factors showed no consistent relationship. All cases had left-sided posterolateral diaphragmatic defects. Dyspnea, cyanosis and dextrocardia was the classical triad present in more than 50% cases. The commonest herniated contents were the small intestinal loops and the left lobe of liver. Associated congenital multiple anomalies related to neural axis, skull, vertebral column and cardiovascular system were noted in 30% cases and were major contributory factors for perinatal mortality. PMID- 1752678 TI - Urban parents' understanding of fever in children: its dangers, and treatment practices. AB - One hundred urban parents were interviewed for their knowledge, attitude and treatment practices towards fever in children. Only 55% parents were aware of the normal body temperature and 23% of the febrile temperature. A total of 58% considered fever as a disease, 91% felt that fever could go on rising if unchecked, and 60% believed that if it is brought down the child would be cured. As home treatment, paracetamol was used by 57% parents, and cold sponging by 29%. Sixty three per cent were of the opinion that a doctor must be consulted for any fever. The understanding of fever and home treatment practices were significantly better in highly educated parents. Above points must be considered while counselling parent of a febrile child, and for formulating health education package for the parents. PMID- 1752679 TI - Cerebrospinal fluid N-acetyl neuraminic acid estimation for early diagnosis and differentiation of bacterial meningitis. AB - Cerebrospinal fluid (CSF) analysis for free, bound and total N-Acetyl Neuraminic Acid (NANA) as well as serum NANA was done in 68 patients of bacterial meningitis, of which 37 cases were of pyrogenic meningitis and 31 of tuberculous meningitis. Ten patients were included in the control group. The free NANA levels were increased in only pyogenic meningitis, independent of protein levels but the bound form increased with the increase in CSF proteins. The increase of free NANA in CSF of pyogenic meningitis patients was not related to the cell count or sugar content in CSF or to the duration or severity of illness. This finding can be of great help in differentiating cases of pyogenic meningitis, particularly partially treated patients, who may have ambiguous pictures of CSF analysis, from the cases of tuberculous meningitis. PMID- 1752680 TI - Poisoning in children. AB - This study is a retrospective analysis of 670 cases of poisoning (including phenothiazine toxicity) admitted to this hospital in the past six years, accounting for 0.9% of all pediatric admissions. Nearly half (45%) of the cases were in the age group of 1-4 years. Medicines and chemicals were the commonest agents (53%), followed by pesticides (15%), kerosene (11.2%), plant poisons (9.4%), food poisoning (3.9%) and corrosives (1.9%). Accidental poisoning was the commonest (70%) followed by iatrogenic (29.6%) and suicidal (0.4%). Overall mortality was 1.8%. Stress is laid on judicious use of phenothiazines as antiemetics and replacing them with drugs of lesser toxicity. PMID- 1752681 TI - Drugs used in the treatment of childhood psychiatric disorders. PMID- 1752682 TI - Health education in school children. PMID- 1752683 TI - Jejunal diaphragm. PMID- 1752684 TI - Congenital cleft hand and cleft foot. PMID- 1752685 TI - Carbamylphosphate synthetase-I deficiency in a newborn: survival after early diagnosis and therapy. PMID- 1752686 TI - Transfusion associated malaria in endemic areas. PMID- 1752687 TI - Epidemic hysteria masquerading as food poisoning. PMID- 1752688 TI - Use of corticosteroids in bacterial meningitis. PMID- 1752689 TI - Do not clamp the umbilical cord too close. PMID- 1752690 TI - Pediatrician: the custodian of the child consumer. PMID- 1752691 TI - Nyctalopia. PMID- 1752692 TI - The relationship between development of lung inflammation and changes in bone marrow populations in guinea-pigs following inhaled antigen challenge. AB - Sensitised guinea-pigs were exposed to aerosolised antigen. The resultant cellular infiltration into the lung was assessed in lung tissue and bronchoalveolar lavage fluid 6, 24, 72 h and 7 days later. An early neutrophil infiltration peaking at 6 h was succeeded by eosinophil migration which persisted for 7 days, at which time some of the eosinophils appeared immature. The lung eosinophilia was accompanied by an initial fall in eosinophilic cells in the bone marrow, followed by an increase in this population. Treatment with dexamethasone (25 mg/kg i.p.) given daily for 7 days after antigen challenge reduced the lung eosinophilia and observed bone marrow changes. PMID- 1752693 TI - Purification and characterization of Par o I, major allergen of Parietaria officinalis pollen. AB - Par o I, a major allergen of Parietaria officinalis, was purified from the pollen extract. The purified allergen was obtained by ultrafiltration, Sephadex gel filtration and DE-52 ion exchange chromatography: the purified preparation yields a single band in polyacrylamide gel isoelectric focusing (PAG-IEF), sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting, a single immunoprecipitation arc in crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) and a single peak in size exclusion high-performance liquid chromatography (HPLC). Par o I is a glycoprotein with a protein to carbohydrate ratio of 100:21. The molecular weight, determined by SDS-PAGE, Sephadex G-50 gel filtration and size exclusion HPLC, varied between 13.5 and 14.5 kDa according to the method employed. The isoelectric point was 4.6. The amino acid composition and the sequence of the first twelve N-terminal residues were determined. The allergenicity was assayed in vivo and in vitro. 29/29 Parietaria-allergic patients were skin positive to Par o I and possessed high level of specific serum IgE antibody as it determined by radioallergosorbent test (RAST). Par o I contained dominant epitopes for human IgE as inhibited to 85% the pollen extract RAST performed with a pool of sera of allergic patients. The RAST inhibitory activity was not abolished by deglycosylation. PMID- 1752694 TI - Role of interleukin-5 in local accumulation of eosinophils in mouse allergic peritonitis. AB - The injection of ragweed pollen extracts into the peritoneal cavity of actively immunized mice caused an accumulation of eosinophils in the cavity. We investigated the role of interleukin-5 (IL-5), one of the T-cell-derived factors, in this in vivo local accumulation. Ciclosporin, an immunosuppressant that mainly suppresses T cell functions, dose-dependently inhibited the in vivo local accumulation. Injections of the neutralizing antibody to IL-5 into the cavity decreased the number of the accumulating eosinophils. When the peritoneal cells of the immunized mice were cultured in the presence of the antigen in vitro, IL-5 activity was detected in the culture supernatant. The results indicate that IL-5 plays an important role in the in vivo local accumulation of eosinophils after an antigen challenge. PMID- 1752695 TI - Antiphospholipid antibodies reactive with bromelain-treated mouse erythrocytes in mice, rats and rabbits. AB - It has been reported that normal mice have a large number of B cells against bromelain-treated mouse erythrocytes (BrMRBC) and the anti-BrMRBC antibodies are reactive with liposomes of phosphatidylcholine and a phospholipid moiety of low density lipoproteins from chicken egg yolk (EyLDL). In this study, we detected anti-BrMRBC hemolytic antibodies in the normal sera of rats and rabbits as well as mice. The antibodies in all the three species of animals bound to the columns of EyLDL. The EyLDL-binding antibodies could react with both liposomes of phosphatidylcholine and BrMRBC. The immunization with EyLDL evoked a vast production of anti-BrMRBC antibodies in rats and rabbits as well as mice. The anti-BrMRBC antibodies in the immunized animals could also react with liposomes of phosphatidylcholine. These findings suggest that rats and rabbits have the equivalent of mouse anti-BrMRBC B cells. PMID- 1752696 TI - In vitro formation of complement activation products by lipopolysaccharide chemotypes of Salmonella minnesota. AB - We have applied immunoassays for complement activation products C4d, fragment Bb and the protein S-C5b-9 neoantigen (S-MAC) to assess activation of classical, alternative and terminal pathways, respectively, by lipopolysaccharides (LPS) from the smooth strain (SS) of Salmonella minnesota and the shallow rough (core) mutants R60, R345, R5 and R7. Incubations of sera (n = 6) with LPS generated small and insignificant quantities of Bb and S-MAC in the case of Rb, Rc and Rd chemotypes and slightly greater quantities with Ra. SS-LPS brought about significant (p = 0.01) increases in the formation of both Bb and S-MAC. No significant changes were observed in the concentration of C4d. Polymyxin B enhanced Bb and S-MAC production by SS-LPS, optimally at the lowest concentration of polymyxin B studied, 10 ng/ml. These data confirm and extend observations about complement activation by LPS and suggest that immunoassay may be useful in studying mechanisms of complement activation. PMID- 1752697 TI - Activation of human vascular endothelial cells by IFN-gamma: acquisition of HLA class II expression, TSST-1-binding activity and accessory activity in T cell activation by the toxin. AB - Human umbilical vascular endothelial cells (HUVEC) stimulated with recombinant human IFN-gamma were investigated for expression of HLA class II molecules, toxic shock syndrome toxin-1 (TSST-1)-binding activity and accessory cell (AC) activity in TSST-1-induced T cell activation. HUVEC stimulated with recombinant human IFN gamma ranging from 10 to 1,000 units/ml for 72 h express HLA class II molecules. Intensity of the expression was dependent on the concentration of IFN-gamma. HUVEC stimulated with 1,000 units/ml of IFN-gamma for 72 h exhibited 125I-TSST-1 binding that was blocked by the unlabeled toxin and monoclonal antibodies (mAb) to DR/DP. The activity was not removed by paraformaldehyde fixation. The IFN gamma-stimulated HUVEC exhibited AC activity in TSST-1-induced IL-2 production by T cells from human peripheral blood mononuclear cells. The activity was blocked by mAb to DR. The above two activities were also observed in L cells transfected with DR2 genes but not in the unstimulated HUVEC and control L cells. In view of the fact that TSST-1 binds directly to HLA class II molecules and activates human T cells in association with HLA class II molecules on AC, it is likely that the acquisition of TSST-1-binding activity and AC activity in the toxin-induced T cell activation is mediated by the expression of HLA class II molecules. Vascular endothelial cells may play an important role in the development of pathological changes in TSS patients. PMID- 1752698 TI - Spontaneous monokine release by alveolar macrophages in chronic sarcoidosis. AB - In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration greater than 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 ratio was higher in the active than in the inactive group without reaching statistical significance. TNF alpha as well as IL-1 is spontaneously released by AM of the active group 2,099 +/- 518 pg/ml TNF alpha/10(6) cells/24 h and 8/13 (IL-1+/total) respectively. In the inactive group the AM release 375 +/- 246 pg/ml TNF alpha/10(6) cells/24 h which is in the range of the control and 1 out of 5 patients was IL-1-positive. There was no correlation between the monokine release and any parameter of T-cell alveolitis. These data support the hypothesis that the inflammatory process in chronic sarcoidosis is dominated by the activity of AM and that this activity determines the course of the disease. PMID- 1752699 TI - Tumor necrosis factor alters cytoskeletal organization and barrier function of endothelial cells. AB - Treatment of human umbilical cord vein endothelial cells with tumor necrosis factor results in marked changes in cell shape and cytoskeletal organization. After 4 h of treatment, these cells loose reciprocal contacts with the formation of intercellular gaps. This retraction reaches a maximum after 6 h when most stress fibers staining for F-actin disappear and vinculin becomes diffused in the cytoplasm. Such changes spontaneously reverse after 24 h in the presence of tumor necrosis factor or after 2 h of incubation in fresh medium. After treatment with tumor necrosis factor, endothelial monolayers become permeable to albumin because of gaps that form between cells. Normal human serum, plasma alpha 1-proteinase inhibitor and an anti-inflammatory peptide that decrease synthesis of platelet activating factor inhibit the changes induced by tumor necrosis factor. Furthermore, receptor antagonists of platelet-activating factor have the same effect. These findings suggest that platelet-activating factor is a secondary mediator responsible for the changes in cell shape and cytoskeletal organization, and for the leakiness of endothelial monolayers. PMID- 1752700 TI - Serum levels of interleukin 4, interleukin 6 and interferon-gamma following in vivo isotype-specific activation of IgE synthesis in humans. AB - It is now generally accepted that interleukin 4 (IL4), interleukin 6 (IL6) and interferon-gamma (IFN gamma) play main roles in the regulation of human IgE synthesis. This concept is based mainly on in vitro data. To obtain corresponding in vivo data, we determined IL4, IL6 and IFN gamma by immunoassays in sera collected from 4 atopic patients following a clinical trial of selective IgE apheresis (plasmaimmunoadsorption). This treatment removes several milligrams of IgE from patient's blood and is suggested to induce strong and isotype-specific activation of the IgE system. Serum IgE levels restored rapidly within 3-5 days after IgE apheresis. However, very low and constant levels of IL4 (from less than 50 to 130 pg/ml) and IL6 (from less than 300 to 920 pg/ml) were detected in the sera of the treated patients. Serum IFN gamma was absent before treatment (concentrations less than 0.5 U/ml) and increased to low but detectable levels (0.90 and 8.05 U/ml) on the day following the last IgE apheresis in 2 of 4 patients. In our opinion, the data presented argue against in vivo participation of IL4 and IL6 in the activation of the human IgE system, at least in atopic patients under constant allergen exposure. PMID- 1752701 TI - Strongyloidiasis influences the elevation of adult T-cell leukemia-associated antigen antibody titer. AB - We have carried out a seroepidemiological study on the infectious situation of adult T-cell leukemia and strongyloidiasis in Okinawa and in the south-western islands of Japan. The mean titer of adult T-cell leukemia virus-associated antigen (ATLA) antibody of human T-lymphotropic virus type-1 (HTLV-1) carriers with strongyloidiasis was significantly higher than that of HTLV-1 carriers without strongyloidiasis. This suggests the possibility that strongyloidiasis is also associated with an elevation of the ATLA antibody titer. PMID- 1752702 TI - Chemotactic cytokine gene expression and production induced in human monocytes by membrane proteoglycans from Klebsiella pneumoniae. AB - The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on production of the chemotactic cytokine, IL-8, and monocyte chemotactic protein (MCP) by human peripheral blood monocytes. Exposure of human peripheral blood monocytes to MPG in vitro induced high levels of mRNA transcripts for IL-8 and MCP, as assessed by Northern blot analysis. Cytokine gene expression was associated with the production of chemotactic activity in the supernatants. The levels of IL-8 and MCP expression induced by MPG were comparable with those elicited by LPS. Induction of chemotactic cytokines in mononuclear phagocytes may play a role in the immunomodulatory activity of MPG. PMID- 1752703 TI - In vivo stimulation of thymocyte proliferation by thymocyte growth peptide (TGP). AB - Chromatographically pure thymocyte growth peptide (TGP) was injected into one of the two thymus lobes of guinea pigs. Pulse labelling of DNA-synthesizing cells was obtained by an intracardial injection of bromodeoxyuridine (BrdUrd). After 24 and 48 h, the frequency of labelled cells was increased in the TGP-treated lobe in comparison with the control lobe. At 24 h, the increase was found in non rosetting, large, low-density cells, the population containing the highest frequency of DNA-synthesizing cells. At 48 h, labelled rosette-forming, small, high-density cells appeared in an increased frequency in the TGP-treated lobe. Serum thymic factor (FTS), which is structurally related to TGP, did not produce similar effects. The results show that TGP is active in vivo and stimulates proliferation of cycling thymic precursor cells which then are transformed into small thymocytes. PMID- 1752704 TI - Immunomodulatory action of levamisole--I. Structural analysis and immunomodulating activity of levamisole degradation products. AB - In our laboratory we observed that solutions of levamisole (LMS) stored at 4 degrees C consistently enhanced the lymphocyte proliferation response to concanavalin A (Con A) more than freshly prepared solutions did. To determine if the increased immunopotentiation observed with the stored solutions of LMS was due to products formed from LMS, we assessed the stability of LMS when stored at 4 or 37 degrees C at pH 6, 7, 7.5 and 8. Analysis of the various solutions by high pressure liquid chromatography demonstrated that LMS decomposes during storage in neutral and alkaline conditions to form three products. The formation of the products was accelerated by increasing the temperature from 4 to 37 degrees C. The three degradation products were purified by preparative high pressure liquid chromatography and their structures determined by mass spectrometry, infrared spectrometry and homo- and heteronuclear two dimensional nuclear magnetic resonance spectroscopy. The degradation products, denoted as No. 1, No. 2 and No. 3, based on their high pressure liquid chromatography retention times, were identified as: No. 1, 3-(2-mercaptoethyl)-5-phenylimidazolidine-2 one; No. 2, 6-phenyl-2,3-dihydroimidazo (2,1-b) thiazole and No. 3, bis [3-(2-oxo 5-phenylimidazolidin-1-yl) ethyl] disulfide. Product 2 significantly enhanced murine lymphocyte proliferation responses to concanavalin A (Con A) at concentrations between 0.5 and 10.0 micrograms/ml (whereas the optimum concentration of LMS is 10-100 fold higher (50-100 micrograms/ml)). Products 1, 2 and 3 significantly inhibited the lymphocyte proliferative response at concentrations greater than 2.2, 10.0 and 10.0 micrograms/ml, respectively. These studies indicate that under relatively mild conditions, including physiological conditions, LMS may decompose to products which inhibit or enhance lymphocyte responses to Con A. PMID- 1752705 TI - Immunomodulatory action of levamisole--II. Enhancement of concanavalin A response by levamisole is associated with an oxidation degradation product of levamisole formed during lymphocyte culture. AB - Previously we determined that levamisole (LMS), when stored for a period of time, breaks down to three degradation products at neutral and alkaline pH. At low concentrations (10(-6) M), Product 1 inhibits the lymphocyte response to concanavalin A (Con A). Product 2 enhances the response and Product 3 has no effect. At higher concentrations (10(-5) M) all three products inhibit the response. To determine if these products are formed in culture media under culture conditions (e.g. in RPMI-1640 bicarbonate buffered medium, 37 degrees C, pH 7.0-7.5, during a 72 h culture period), we added freshly prepared LMS solutions to culture media with and without lymphocytes present and maintained the pH at 7.0, 7.25 or 7.5 by varying the amount of CO2 present. Periodically over a 72 h period, aliquots of the media were removed and analyzed for the presence of LMS and the three degradation products. Within 4 h, two of the degradation product began to form in culture media with or without lymphocytes present. Product No. 1, 3-(2-mercaptoethyl)-5-phenylimidazolidine-2-one or dl-2 oxy-3-(2-mercaptoethyl)-5-phenylimidazolidine (OMPI), which inhibits the lymphocyte response to concanavalin A (Con A) at concentrations above 0.4 micrograms/ml, was formed at pH 7.0, 7.25 and 7.5, but the compound did not reach inhibitory concentrations in the lymphocyte cultures during the 72 h culture period. Product No. 2, 6-phenyl-2,3-dihydroimidazo (2,1-b) thiazole, which enhances the Con A response between concentrations of 0.5 and 10 micrograms/ml, was detected at concentrations between 2.5 and 3.5 micrograms/ml at pH 7.25 and 7.5. Product 2 was not detected in cultures at pH 7.0 and subsequently when we cultured lymphocytes with freshly prepared LMS and maintained the pH at 7.0, no significant enhancement of the Con A response was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752706 TI - An enzyme-linked immunosorbent assay of anti-sheep red blood cell antibodies of the classes M, G, and A in the rat. AB - In order to investigate the immune system as a possible target for toxicity by chemicals, functional assays of the immune system are required. Sheep red blood cells (SRBC) are widely used as an antigen to study the immune competence of animals. Since routine toxicology includes data mainly provided with rat toxicity studies, there is a need for easy, specific, and reproducible assays of antibody responses to sheep erythrocytes in the rat. This report describes an enzyme linked immunosorbent assay (ELISA) of anti-SRBC antibodies of the classes M, G and A in the serum of rats. Antigen preparations, prepared from ghosts of sheep erythrocytes by extraction with KCl, were used to coat the bottom of wells in 96 well microtiter plates. Serum samples from rats, that were immunized with sheep erythrocytes, were titrated on these plates, using specific polyclonal antibodies to rat immunoglobulins M and G, to which peroxidase was conjugated. Immunoglobulin A was assayed, using monoclonal anti-rat IgA antibodies, and polyclonal rat anti-mouse IgG that was conjugated with peroxidase. The results indicate that the ELISA of serum titers of IgM, G and A to sheep erythrocytes is an easy and reliable method, that can be used to detect the effects of chemicals on the immune system of the rat. PMID- 1752707 TI - Distinctive effects of three different modes of exercise on oxygen uptake, heart rate and blood lactate and pyruvate. AB - We intended to investigate the effects of different modes of exercise on oxygen uptake (VO2), the heart rate and the levels of lactate and pyruvate in venous blood. For this, untrained male subjects performed three modes of exercise with a treadmill (TR), a bicycle ergometer (UP) and a supine leg ergometer (SU). The percentage of maximal oxygen uptake (% VO2max) and VO2/weight for TR were significantly higher than those for UP or SU at lactate levels of 2, 3 and 4 mmol/l. The heart rate was also higher for TR than for SU at these lactate levels. The correlations of blood lactate with % VO2max, VO2/weight and the heart rate were significant for TR and SU, but not for UP. Blood lactate levels were lower for TR than for SU or UP at 60, 70, 80% VO2max, whereas the values for UP were lower than those for SU only at 60% VO2max. Blood pyruvate levels were always lower for TR than for SU. The ratios of lactate/pyruvate differed for TR and SU only at 60% VO2max. For a given mode of exercise, blood lactate and the ratio of lactate/pyruvate increased with an increase in % VO2max, but those of pyruvate did not. These results reveal that the relationships between any two of lactate, pyruvate, VO2 and the heart rate are different at different modes of exercise, and that blood lactate depends on adaptation of muscles to a mode of exercise rather than on the quantity of muscles mobilized. PMID- 1752708 TI - Effects of caffeine ingestion on performance and anaerobic metabolism during the Wingate Test. AB - In order to determine the effects of caffeine ingestion on performance and metabolic responses during supramaximal exercise, six healthy volunteers performed the Wingate Anaerobic Test twice. Sixty min before each trial, while in a fasting state, they took capsules containing either caffeine (5 mg/kg) or a placebo, according to a single blind and randomized procedure. Caffeine administration did not significantly change either maximal anaerobic capacity (AC) or power (AP) and power decrease (PD). It did, however, induce significant (p less than 0.05) increases in both catecholamine and blood lactate levels as compared to values obtained after placebo administration. Moreover, maximal blood lactate occurred earlier (p less than 0.05), and lactate output seemed to be greater with caffeine (p less than 0.01). There was a strong correlation, both with and without caffeine, between epinephrine and lactate levels (r = 0.81) and between both AP and AC and lactate levels. These data suggest that caffeine, essentially via epinephrine, modifies glycolytic metabolism but fails to improve performance during the Wingate Anaerobic Test in nonspecifically trained subjects. PMID- 1752709 TI - Training-overtraining. A prospective, experimental study with experienced middle- and long-distance runners. AB - Overtraining may be one frequent cause of stagnation or decrease in performance capacity of athletes. Israel (19) differentiates between addisonoid (parasympathetic) and basedowoid (sympathetic) overtraining, characterized by inhibition or excitation. We tried to induce an overtraining syndrome in 8 experienced middle- and long-distance runners, based on an increase in training volume from an average 85.9 km (week 1) to 115.1 km (week 2) and 143.1 km (week 3) to 174.6 km per week (week 4). The influence of this training on cardiovascular, metabolic and hormonal parameters was examined with special respect to plasma and urinary catecholamines. Laboratory testing including graded treadmill running was performed on the days 0, 14 and 28. Training was held six days each week, with nearly 30 km per day in the fourth week. A stagnation in endurance performance capacity (running velocity at the aerobic-anaerobic transition range) and a decrease in maximum working capacity were observed in 6 and a stagnation in 2 of the 8 sportsmen, indicated by a decrease in total running distance from 4719 + 912 m to 4361 + 788 m during incremental treadmill ergometry. The sportsmen could neither improve nor could they even approximately reach their personal records during the subsequent competitive season. Subjective complaints, classified on a four-point scale, increased from 1.2 (week 1) to 3.2 in week 4. Glucose, lactate, ammonia, glycerol, free fatty acids, albumin, LDL, VLDL cholesterol, hemoglobin level (transient), leukocytes, and heart rate (before and during exercise) decreased significantly. Urea, creatinine, uric acid, GOT, GPT, gamma-GT, serum electrolytes (except phosphate and calcium) remained constant at the measuring times, CPK was elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752710 TI - Hematological comparison of iron status in trained top-level soccer players and control subjects. AB - The aim of the present study was to compare the iron status of 19 top-level soccer players and 20 male control subjects. All players showed no impairment of physical performance and had a dietary iron intake adequate to cover the iron losses. Serum iron, TIBC, % transferrin saturation and serum ferritin were not significantly different in athletes and controls: serum haptoglobin was significantly lower in the former than in the latter, the result probably indicating an increase in resting intravascular hemolysis. Since the formed Hb-Hp complex is taken up and metabolized by hepatocytes, it has been suggested that in soccer players a redistribution of iron stores occurs among tissue compartments. A multiparametric hematological monitoring of iron metabolism, just as in runners, is therefore necessary in these athletes, too, in order to detect subjects at risk of real iron deficiency. The pharmacological iron supplementation should be limited to these subjects and only when clinical evidence of reduced tissue iron supply is present. PMID- 1752711 TI - Effects of maximal and submaximal exercise under normoxic and hypoxic conditions on serum erythropoietin level. AB - This study was carried out to investigate the influence of different exercise regimens on serum immunoreactive erythropoietin concentration (EPO). The same untrained male subjects performed bouts of maximal and submaximal exercise (60 min at 60% of maximal performance) under normoxia (n = 10) and normobaric hypoxia (PIO2 92 mmHg, n = 9). Five of them were exposed to hypoxia for 90 min under resting conditions (RTH). [EPO] was unchanged up to five hours after maximal (MEN) and submaximal (SEN) exercise under normoxia. After RTH, [EPO] increased after 3 hours by 5.0 mU/ml (p less than 0.01). Submaximal exercise under hypoxia (SEH) led to a similar increase in [EPO] (after 3 hours: + 5.5 mU/ml), which remained elevated the following days (after 24 h: + 6.1 mU/ml, 48 h: + 5.3 mU/ml; ANOVA p less than 0.001). Maximal exercise under hypoxia (MEH) had no significant effect. The results indicate that exercise has no immediate effect on serum [EPO], whereas the higher EPO level one and two days after SEH could result from the occurring hemodilution as is indicated by a slight negative correlation between [EPO] and Hct (r = 0.59, p less than 0.001). The number of reticulocytes increased after all hypoxic experiments and after MEN without any correlation to [EPO]. PMID- 1752712 TI - Iron supplementation and running performance in female cross-country runners. AB - The purpose of this study was to determine the effects of two weeks of high dosage iron supplementation on various blood iron indices and metabolic parameters in non-anemic, iron-depleted competitive female cross-country runners. The subjects were highly trained members of the Colorado State University cross country team and were completing 40 to 50 miles of training weekly. A pretest, post-test single-blind crossover design was employed. Upon collection of baseline exercise blood and metabolic data, five subjects were randomly assigned to iron supplementation (650 mg ferrous sulfate; 130 mg elemental iron) and five subjects to placebo treatment. At two weeks the treatments were reversed. Exercise blood and metabolic data were collected at two-week intervals. Dietary iron intake was assessed using a three-day dietary survey. Dietary analysis revealed deficiencies in vitamin B-6, iron, magnesium, and zinc according to USRDA standards. Baseline blood samples revealed no deficiencies in iron storage or transport proteins. Two weeks of iron supplementation resulted in no significant increases in blood iron indices. Metabolic parameters related to running performance were also unchanged after iron supplementation. High dosage, short-term iron supplementation appears to have no effect on blood or metabolic parameters in iron-depleted but non anemic female cross-country runners. PMID- 1752713 TI - Effects of technique and pole grip on physiological demands of roller skiing on level terrain. AB - This study evaluated the physiological responses to roller skiing with three different techniques, and compared the physiological responses during roller skiing with a standard pole grip and an innovative "anatomical" pole grip. Data were collected on ten experienced cross-country ski racers while roller skiing with the double pole, V1 skate, and kick double pole techniques on a flat track at mean (+/- SD) velocities of 14.6 +/- 0.2, 16.4 +/- 0.3, and 18.0 +/- 0.4 km.h 1. The kick double pole technique induced the highest (p less than 0.05) oxygen uptakes, heart rates, and ventilations. The double pole technique elicited the lowest (p less than 0.05) oxygen uptakes, and the V1 skate technique elicited the lowest (p less than 0.05) perceived effort and respiratory exchange ratios. Comparison of the two pole grips showed no differences in the physiological responses and perceived effort. While the V1 skate technique is not the most economical roller skiing technique on flat ground, the lower associated perceived effort and respiratory exchange ratios may at least partially account for the general preference of cross-country ski racers to use the V1 skating technique rather than the double pole technique on flat terrain. PMID- 1752714 TI - Tennis: a physiological profile during match play. AB - Heart rate (HR), hematocrit, hemoglobin, blood glucose, and plasma concentrations of lactate, cortisol, and testosterone were monitored in 10 male subjects (Division I, 20.3 +/- 2.5 yrs, VO2max: 58.5 +/- 9.4 ml.kg-1.min-1) during singles tennis and a treadmill test. During the on-court session, HR was 144.6 +/- 13.2 beats.min-1 for the 85 min of play. Plasma lactate rose 50% from a post-warmup value of 1.6 +/- 0.6 mmol.l-1 to 2.3 +/- 1.2 mmol.l-1 during play (p greater than 0.05). Blood glucose slightly decreased (8%, p greater than 0.05) from a pre exercise value of 4.6 +/- 0.8 mmol.l-1 as a result of the 10-min warmup. This was followed by a 23% rise (p less than 0.05) from 4.2 +/- 1.0 mmol.l-1 to 5.2 +/- 0.6 mmol.l-1, measured after the first 30 min of play. Blood glucose subsequently remained steady at slightly above the pre-exercise value. Plasma cortisol rose (9%, p greater than 0.05) during the warmup and subsequently decreased (p less than 0.05) from a post-warmup value of 558.2 +/- 285.2 nmol.l-1 to 337.1 +/- 173.3 nmol.l-1 (a 40% decrease), and remained decreased during recovery. Plasma testosterone rose 22% (p less than 0.05) from pre-exercise to recovery (13.5 +/- 3.8 nmol.l-1 and 16.5 +/- 2.6 nmol.l-1, respectively). Although tennis is characterized by periods of high-intensity exercise, the overall metabolic response resembles prolonged moderate-intensity exercise. PMID- 1752715 TI - The effect of warm-up on responses to intense exercise. AB - The purpose of this study was to determine if prior physical activity (warm-up) affected physiological responses to intense exercise. Eight highly trained collegiate swimmers performed a paced 365.8-m (440 yds) intense swim (mean +/- SE, 94.4 +/- 3.3% VO2max) 5 min after the following warm-up conditions: trial N, no warm-up; trial S, an intensity-specific interval set (4 x 45.7 m with one-min rest intervals at the intense swim pace); trial M, a mild-intensity, long duration swim (1371.6 m at 64.7 +/- 3.3% VO2max); and trial MS, a mild-intensity, long-duration swim (1188.7 m at the same pace as trial M) followed by the intensity-specific interval set (trial S). When comparing trial N with trials M and MS, stroke distance (m/stroke) was significantly (p less than 0.05) lower during the last 91.4 m of the intense, paced swim and 3-, 5-, 8- and 10-min recovery blood lactate levels and one-minute recovery heart rates were significantly elevated (p less than 0.05). There was no significant difference (p greater than 0.05) in stroke distance during the final 91.4 m of the intense swim between trials S and N. There were no significant differences for any variables between trials M and MS. These results suggest that a warm-up consisting of mild intensity, long-duration exercise was beneficial compared to no warm-up and that intensity-specific exercise was not a vital component of warm-up. Although performance was not directly measured, these data demonstrate the benefit of warm up. PMID- 1752716 TI - Effects of training and training cessation on insulin action. AB - Physical training has been shown to improve glucose tolerance and insulin action. In the present study, insulin action was determined using the euglycemic clamp technique in six trained male athletes compared with six untrained controls matched by age, sex, and weight at 14, 38, and 86 hours and at 6 days after cessation of exercise. The rate of insulin-mediated glucose uptake (glucose disposal) was 9.40 +/- 0.46 mg.kg-1.min-1 (mean +/- SEM) for the athletes at 14 h after the last exercise bout, compared with 6.80 +/- 0.86 mg.kg-1.min-1 obtained for the untrained controls (p less than 0.01). Glucose disposal was gradually decreased to 7.78 +/- 0.87 mg.kg-1.min-1 at 38 h, 6.82 +/- 0.49 mg.kg-1.min-1 at 86 h and to 7.11 +/- 1.00 mg.kg-1.min-1 at 6 days after cessation of physical training. At 38 h, 86 h, and 6 days of detraining, glucose disposal exhibited by training athletes did not differ significantly from untrained controls. These results suggest that physical training increases insulin action, and that this effect could be reversed to the control levels within 38 h after detraining. PMID- 1752717 TI - Exercise changes in plasma tryptophan fractions and relationship with prolactin. AB - In the past the hypothesis was advanced that plasma tryptophan fractions mediate behavioural and neuroendocrine effects of exercise. To assess changes in free and total plasma tryptophan levels during and after exercise over a time period, and possible functional implications, 6 male volunteers were subjected to an endurance test of 1 hour duration on a bicycle ergometer at a work load below the 4 mmol/l lactate threshold. Total and free plasma tryptophan were determined by high-performance liquid chromatography with electrochemical detection, prolactin by radioimmunoassay, glycerol and nonesterified fatty acids (NEFA) by enzymatic methods. No significant changes in total tryptophan were found. Free plasma tryptophan increased significantly (23%, p less than 0.01) from 40 to 60 minutes of exercise. Highest levels were observed after 10 minutes of recovery (50% against preexercise). Prolactin levels correlated with free plasma tryptophan throughout the test (r = 0.77, p less than 0.001, all measured values) and during recovery (10 minutes: r = 0.88, p less than 0.05; 20 minutes: r = 0.86, p less than 0.05). These findings may further support the hypothesis that changes in peripheral amino acid concentrations may influence physiological reaction of exercise mediated by brain systems. PMID- 1752718 TI - Serum and saliva cortisol responses and blood lactate accumulation during incremental exercise testing. AB - In six male physically active subjects the adrenocortical and metabolic changes in response to incremental exercise testing were investigated. Blood and saliva samples were taken at rest, at the end of every workload (duration 4 min with 50 W increment), immediately and 10 min after 1 min all out spurt on the electrically braked cycle ergometer. Both saliva and serum cortisol were measured as well as blood lactate. The cortisol response in serum and in saliva showed similar dynamics (r = 0.86, p less than 0.001, n = 50) at submaximal work. At maximal work the serum cortisol concentration showed a transitory decrease, which was not manifested in saliva. It is hypothesized that a factor related to the metabolic acidosis masks the actual adrenocortical response in the serum but not in saliva. Correlation analysis revealed a positive relation between lactate and cortisol in serum (r = 0.56, p less than 0.01, n = 50) and saliva (r = 0.70, p less than 0.01, n = 50). Apparently, salivary cortisol closely reflects plasma free cortisol level, presenting advantage over total cortisol measurements. Moreover salivary measurement will permit studies in their authentic settings and should assist attempts to understand the nature of the adrenocortical function in exercise. PMID- 1752719 TI - Exercise-induced changes of endorphin contents in hypothalamus, hypophysis, adrenals and blood plasma. AB - Changes of alpha-, beta-, and gamma-endorphin contents were determined in hypothalamus, hypophysis, adrenals and blood plasma in Wistar rats. Four hours of swimming in water at 32 +/- 1 degrees C caused a decrease of the beta-endorphin content in hypophysis and hypothalamus. In adrenals, beta-endorphin did not change. Changes of alpha- and gamma-endorphins were not parallel to alterations of beta-endorphin. In blood plasma, levels of both alpha- and gamma-endorphins were elevated. After 7 days of swim training, 4 hours of swimming caused a slight increase of alpha-, beta- and gamma-endorphin levels in hypophysis as well as a pronounced increase of alpha- and beta-endorphins in adrenals. In hypothalamus, beta-endorphin content was decreased, but alpha-endorphin content was on the level of sedentary controls, gamma-endorphin content doubled. The levels of endorphins in blood were higher than after a single swimming bout. It was concluded that during acute exercise the activation of the opioid system is mainly based on the augmented release of beta-endorphin. In daily repeated exercise the production of beta-endorphin increases and exceeds the elevated release in hypophysis and adrenals. PMID- 1752720 TI - The effect of exercise at various temperatures on salivary levels of immunoglobulin A. AB - The purpose of this investigation was to determine the effect of ambient temperature on the salivary immunoglobulin A (s-IgA) response to submaximal exercise. Nine adult males (x age +/- SD = 22 +/- 2 yrs) volunteered to perform an incremental treadmill test to exhaustion for the determination of VO2max and three 30-minute treadmill runs at 80% VO2max in an environmental chamber at temperatures of approximately 6, 19 and 34 degrees C. Saliva samples were collected prior to each submaximal workbout as well as immediately and 1 hr post exercise. A 2 within subjects factors (temperature, sample time) repeated measures ANOVA indicated no significant interaction or main effects for sampling time or temperature. The results of this study indicated that 30 minutes of non competitive exercise at temperatures ranging from 6 to 34 degrees C had no effect on s-IgA. These findings suggest that moderate intensity exercises at a wide range of ambient temperatures does not increase the susceptibility to upper respiratory infection by decreasing s-IgA. PMID- 1752721 TI - The effect of increased functional load on the activation of satellite cells in the skeletal muscle of adult rats. AB - The comparison of the number of satellite cells in the fast oxidative glycolytic muscle fibers of m. quadriceps femoris in males of normal Wistar rats aged 16-17 weeks (5 animals) and rats trained for endurance (5 animals) was made. After six weeks of treadmill running at a speed of 35 m/min in an increasing regimen, the number of satellite cells in trained animals (9.59 +/- 1.09%) increased over 2.5 fold in comparison to controls (3.41 +/- 0.26%) within 24 hours. At the ultrastructural level complete and focal injuries of some muscle fibers and the partial denervation of individual muscle fibers were recorded in trained rats. It was proposed that the focal functional denervation of muscle fibers could be one of the factors for the activation of satellite cells in endurance exercise. Some trained rats demonstrated small groups of extra- and perisynaptic satellite cells under the basal membrane of muscle fibres, partial detachment of satellite cells from the surface of muscle fiber and presence in the interstitial space cell containing filaments. PMID- 1752722 TI - The effect of amenorrhea on calcaneal bone density and total bone turnover in runners. AB - To examine in athletes the effect of long-term amenorrhea on the skeleton, measurements of calcaneal density and whole body retention of 99mTc imidodiphosphate were made in 42 women who could be allocated to one of 3 groups defined by their level of physical activity and by menstrual status. There was no difference in bone density between eumenorrheic normoactive females and either eumenorrheic or amenorrheic athletes. However, calcaneal density was significantly greater for each group than for previously measured sedentary controls. Total body bone turnover was greater in both eumenorrheic and amenorrheic athletes than in eumenorrheic normoactive women. Sustained, intense physical activity does not significantly increase calcaneal bone density over and above the increase associated with normal levels of activity. This is despite a significant increase in the rate of total body bone mineral turnover. PMID- 1752723 TI - A time-series analysis of longitudinal weight changes in two adult women. AB - This study was conducted to examine individual longitudinal serial trends in body weight of two moderately obese adult women. Self-measured daily weights (over 5000 data points for subject 1 and over 3500 for subject 2) were averaged for each month and analyzed using a time-series analysis approach. The best statistical model for both women indicated a significant upward trend (gain 30 and 22 lb, respectively) interrupted by linear decreases (P less than 0.05) during weight loss programs over the 16- and 10-year observation periods, respectively. The women participated in six and eight weight control programs, respectively, and consistently lost weight, averaging 9.17 +/- 1.85 lb and 8.00 +/- 3.57 lb. Both subjects regained weight after dieting, in a period approximately 2.25 times as long as the diet. Numerous weight fluctuations occurred and one subject lost and then regained 10 percent of her body weight during two 5-year periods. Results are examined in terms of a possible weight increase protection benefit, as well as the deleterious medical potential that may occur with numerous weight loss attempts. Suggestions for future research are provided regarding weight cycling, seasonal variations, set point theory, aging effects, and the use of self-directed weight loss initiatives in conjunction with formal weight reduction programs. This study may serve as a prototype for exploring weight fluctuation using time-series analyses and for further investigating the etiology and clinical management of obesity. PMID- 1752724 TI - Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance. AB - The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues. PMID- 1752725 TI - Effects of gender and age on the heritability of body mass index. AB - We estimated genetic and environmental components of variance of body mass index (BMI) among 7245 same-sexed Finnish MZ and DZ twin pairs aged 18-54 years from the nationwide Finnish Twin Cohort. Age accounted for 20 per cent of variance among men and 26 per cent in women. The contributions of additive genetic effects, shared and non-shared environmental effects on BMI-variance were estimated by LISREL structural equation models. Genetic effects accounted for 72 per cent and 68 per cent of total variance in men and non-pregnant women respectively, while 28 per cent of variance among men and 32 per cent among women was due to non-shared environmental effects. This gender difference was statistically significant. Models including shared environmental effects did not improve model fits. The magnitude of the genetic component of BMI was also analysed separately for each 10-year age group. Models with age-specific parameters for genetic and environmental effects fitted significantly better than models with effects constrained to be equal over age. Our results indicate a substantial genetic component in BMI. However, the magnitude of additive genetic effects decreases with age in both genders. PMID- 1752726 TI - Postural variation of the maximum inspiratory and expiratory pressures in obese patients. AB - Evaluating whether weight is a factor responsible for the decrease of muscle force in the supine position with respect to the upright and sitting positions, we measured maximum inspiratory and expiratory pressures (PImax and PEmax) in these postures in ten obese patients (age 38.7 +/- 9.1 years; height 168.7 +/- 8.9 cm; and weight 139.3 +/- 28.4 kg) and ten normal control subjects (age 38.4 +/- 8.2 years; height 169.3 +/- 7.9 cm and weight 66.9 +/- 11.9 kg.) In both study groups, PImax and PEmax values decreased in the supine posture with respect to upright and sitting positions. Differences between pressures in the various postures were similar for both groups with the exception of PEmax in obese females. The decrease in PEmax values from the sitting to supine positions was greater in obese than control females. Weight, sex and postural changes can influence the generation of maximal expiratory force. PMID- 1752727 TI - Multivitamin prophylaxis in prevention of post-gastric bypass vitamin and mineral deficiencies. AB - One hundred forty patients were followed for a mean 24.2 months after gastric bypass. Postop multivitamin (MV) prophylaxis was recommended for all patients and 90 of 140 patients (64 percent) were regularly compliant. Deficiencies in iron, vitamin B-12 or folate were recognized in 88 of 140 patients (63 percent). Thirty of 45 patients (67 percent) with iron deficiency developed anemia. Forty-three of the 52 patients who did not have deficiencies were regularly taking MV vs 47 of 88 patients who developed deficiencies (P less than 0.001). MV prophylaxis was successful in preventing folate (P less than or equal to 0.05) and vitamin B-12 deficiencies (P less than or equal to 0.02) but did not prevent development of iron deficiency or subsequent anemia. There was no correlation between taking prescribed supplements and resolution of either iron deficiency of anemia. B-12 and folate supplements corrected deficiencies in 73 percent of cases. We conclude that oral MV prophylaxis is useful in preventing folate and B-12 deficiency after gastric bypass. Additional prophylactic iron supplements should be provided for women to prevent iron deficiency and associated anemia. PMID- 1752728 TI - Relationship of fasting serum insulin concentrations with blood pressure in a representative sample of the adult population of the Seychelles. AB - Several studies have been performed to determine if plasma insulin concentration bears a relationship with blood pressure and may be a causative factor in the genesis of hypertension. The results reported were discrepant between studies: insulin was observed to be independently correlated with blood pressure in some studies, whereas no such relationship was observed in others. Serum insulin, whole blood glucose, weight, height, and diastolic and systolic blood pressure of 839 fasting individuals, randomly selected from the adult population of Mahe Island, The Seychelles, were recorded; this population has a high hypertension prevalence rate. The proportion of hypertension was higher in subgroups of individuals with diabetes mellitus (52.4 percent) and with overweight (34.5 percent) than in the general population. Subgroups of individuals with diabetes, excessive weight or high blood pressure had higher mean fasting plasma insulin (13.6 +/- (s.d.) 7.9, 14.0 +/- 8.0, 11.1 +/- 9.7 respectively) than individuals not affected with these conditions (8.1 +/- 4.6 microU/ml). Both systolic and diastolic blood pressure were positively correlated with age, body mass index and fasting blood glucose in a multivariate model. No correlation with insulin was observed. In contrast, in a subgroup of 223 overweight individuals, age, blood glucose and plasma insulin were each positively correlated with blood pressure. It is concluded that, in this cross-sectional study, insulin was not independently correlated with blood pressure except for overweight individuals. PMID- 1752729 TI - Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women. AB - Numerous interrelated metabolic and morphological variables such as plasma insulin levels, glucose tolerance and abdominal obesity are associated with changes in plasma lipoprotein levels. The present study was undertaken to differentiate, using a multivariate approach, the respective contributions of plasma glucose and insulin levels, obesity and regional adipose tissue distribution to the variance in plasma lipoproteins. The study group was composed of 69 healthy premenopausal women (age 35.4 +/- 5.0 years (mean +/- s.d.); percent body fat 40.7 +/- 10.1). Indices of carbohydrate metabolism showed significant univariate correlations with triglyceride (TG) and/or cholesterol (CHOL) content of plasma VLDL, LDL and HDL (P less than 0.05). Multivariate analyses indicated that the explained variance in plasma VLDL-TG (R2 x 100 = 44 percent, P less than 0.05) and LDL-apoprotein (apo) B levels (R2 x 100 = 33.1 percent, P less than 0.08) was entirely accounted for by indices of carbohydrate metabolism and body fat distribution, whereas total body fatness added no significant contribution to these models. Multivariate analyses also revealed that the best possible regression model to predict the variation in plasma HDL2 CHOL levels only included computed tomography-derived deep abdominal adipose tissue area (P less than 0.0001). All other variables were unable to further improve the explained variance in plasma HDL2-CHOL levels. In partial correlation analyses, indices of carbohydrate metabolism and the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma VLDL-TG and LDL-apo B levels after adjustment of VLDL-TG and LDL-apo B for either insulin and glucose levels, or for the WHR (P less than 0.08). After correcting for deep abdominal fat accumulation, no significant correlation was observed between indices of carbohydrate metabolism and plasma HDL2-CHOL levels whereas deep abdominal fat showed significant correlations with HDL2-CHOL levels (P less than 0.05) after correction for indices of carbohydrate metabolism. These results suggest that both disturbances in glucose-insulin homeostasis and abdominal obesity are significantly associated with changes in plasma VLDL-TG and LDL-apo B levels and that these associations are partly independent from each other. These results also indicate that mechanisms other than disturbances in glucose homeostasis and hyperinsulinemia are responsible for the association between the level of deep abdominal fat and plasma HDL2-CHOL levels. PMID- 1752730 TI - Socioeconomic status differences in health behaviors related to obesity: the Healthy Worker Project. AB - Obesity and health behaviors that influence energy balance (diet, exercise, and dieting to lose weight) were examined in a population of 2108 and 2539 working men and women in relation to socioeconomic status (SES). The hypothesis investigated was that the inverse relationship between SES and obesity observed in a number of studies is due to the fact that the distribution of obesity relevant health behaviors differs by social class. Body mass index (BMI), as expected, was found to be inversely related to SES. Higher SES was also associated with several behaviors that contribute importantly to energy balance. High SES respondents reported a lower fat diet, more exercise, and a higher prevalence of dieting to control weight. However, lower smoking rates were observed in upper SES men and women and higher alcohol consumption was reported in upper SES women. Both of these associations appear to be inconsistent with the hypothesis that the inverse association between SES and obesity is caused by differences in health behaviors. In multiple regression analyses, SES remained a significant predictor of BMI after controlling for all measured health behaviors. Weaknesses in the methodologies for measuring health behaviors and possible effects of obesity itself on social mobility are suggested as possible explanations for the residual association between obesity and SES. PMID- 1752731 TI - Adrenalectomy in the Zucker fatty rat: effect on m-RNA for malic enzyme and glyceraldehyde 3-phosphate dehydrogenase. AB - The effects of adrenalectomy with or without replacement doses of corticosterone were examined on the levels of messenger RNA for malic enzyme (ME) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in adipose tissue and liver from Zucker fatty (fa/fa) and littermate lean rats. The levels of both GAPDH and ME mRNAs were increased in the obese rats. Adrenalectomy markedly reduced the m-RNA for GAPDH and ME in Zucker fatty rats to the low levels observed in adrenalectomized lean rats. Corticosterone treatment induced a greater and earlier increase in mRNA levels in adrenalectomized obese rats than in adrenalectomized lean rats. Since the fatty rat represents an autosomal recessive trait, these results are consistent with the hypothesis that the genetic defect is a loss of a modulator of steroid action which normally restricts the response of genes to glucorticoid hormones. PMID- 1752732 TI - Late results after cholesteatoma surgery in early childhood. AB - The incidence of cholesteatoma in children living in an urban area of western Sweden has been studied. The total population of this area is 470,000 out of which 100,000 are children, 16 years or younger. The charts of all the children undergoing cholesteatoma surgery during the time period from 1977 to 1986 were collected and analyzed. Only those patients who had not been exposed to cholesteatoma surgery before were included. In a follow-up study the clinical situation and hearing level have been evaluated 4 years or more after surgery. Nineteen patients, that is an incidence of 0.4 children out of 100,000 inhabitants each year, were found meeting these criteria with an irregular distribution over the 10 year period. During the first two years 11 cases were found, but in the following 8 years only 8 new cases were identified. Intact wall tympanoplasty was used in 10 cases and canal wall down operation in 9 cases. Residual cholesteatoma was detected in 6 cases and recurrent cholesteatoma in one case. Six of these had an intact wall tympanoplasty and all but one were later reoperated with a canal wall down approach. The study reveals a decrease in the incidence of cholesteatoma in children over a 10-year period. The more frequent use of tympanometry and otomicroscopy is a possible explanation. PMID- 1752733 TI - Does the epithelium play a central role in the immune function of rhinopharyngeal tonsils? An immunocytochemical and ultrastructural study. AB - Enlarged adenoids from 10 children with chronic rhinitis and otitis media with effusion have been studied immunocytochemically and ultrastructurally, to better define the possible role of the epithelium and the dendritic accessory cells in the immune activation of lymphoid cells, and provide further insight into the pathogenesis of the disease. The presence within the columnar epithelium of lymphocytes positive for CD8 antigen, and which electron microscopically have been found frequently apposed to degenerating epithelial cells suggests that the latter cells are targets for cytotoxic activity of intraepithelial lymphocytes, rather than being engaged in antigen presentation. Furthermore, the finding of typical dendritic accessory cells, recognized by their typical immunophenotypic and ultrastructural features, in the lamina propria, indicates that antigen presentation is more likely exerted by dendritic accessory cells. This is further supported by the fact that these cells express major histocompatibility (MHC) class II molecules, which are needed for antigen presentation, whereas epithelial cells do not. A possible relationship between epithelial damage and the pathogenesis of adenoidal enlargement is discussed. PMID- 1752734 TI - Paediatric tracheostomy: persistent tracheo-cutaneous fistula following decannulation. AB - A retrospective analysis of 101 children with tracheostomies, all performed for upper airway obstruction and who were decannulated in a single department, is reported. Persistent tracheo-cutaneous fistula occurred in 43% of patients and this was significantly related to age at tracheostomy and duration of tracheostomy. The operation of tracheo-cutaneous fistula closure is described. PMID- 1752735 TI - Assessment of cisplatin-induced ototoxicity using derived-band ABRs. AB - Ototoxicity is an adverse side effect of numerous therapeutic agents (amino glycoside antibiotics, blood chelating agents, diuretics and oncologic drugs) used in treatment of both adult and pediatric patients. Recently, there has been increasing interest in using the auditory brainstem response (ABR) to detect both short-term effects of ototoxicity in adults and long-term effects of drug administration on neonates and children. Since click ABRs have relatively poor frequency selectivity they best approximate the pure-tone hearing threshold in the 2000-4000 Hz frequency range. Hearing loss above or below that frequency range can be present without producing significant abnormalities in the ABR waveform parameters. Frequency-specific ABRs can be obtained using the derived response technique. The purpose of this study was to investigate early cisplatin ototoxicity using both the broadband click and derived ABR and to monitor progressive hearing loss with repeated drug trials in 18 patients studied over a 2-year period. ABRs were obtained serially prior to and following intravenous administration of cisplatin. Derived ABRs were found to be more sensitive than broadband click ABR in detecting early high-frequency hearing loss. For click ABRs, the cumulative dosage of cisplatin at age of ABR examination was correlated with hearing loss in only those patients under 3 years of age. No significant correlation was found between cumulative cisplatin dosage when tested and degree of hearing loss in those patients over 3 years of age. PMID- 1752736 TI - Nasopharyngeal pH monitoring in infants and children with chronic rhinopharyngitis. AB - The etiology and mechanisms involved in determining and/or maintaining the inflammatory process along the airway mucosa remain partially obscure. The role of gastroesophageal reflux (GER) has been demonstrated in some cases of bronchitis and laryngitis especially in children. In adults, GER-related laryngitis has also been mentioned. In children, repeated rhinopharyngitis and otitis media due to GER remain a putative question. In this study, 31 infants and children underwent a day and night nasopharyngeal pH monitoring. Thirteen patients with known GER suffered from chronic or repeated rhinitis or rhinopharyngitis. Eighteen control subjects with or without GER were free of upper airway inflammatory process. In some pathological cases the pH dropped dramatically. The pH drops were more important in most of the GER/rhinitis cases than in controls. Of the reviewed criteria, the percentage of time spent below pH 6 (or pharyngeal acidity index) is the most statistically significant (P less than 0.00005). Thus, the influence of a gastro-esophago-nasopharyngeal acid reflux is strongly suggested in this common pediatric pathology, among other causes. However, the technique used does not allow us to assess the true origin of these pH changes. Further investigation with two-site pH monitoring and larger series of patients are required in order to fully assess the influence of GER on pediatric nasopharyngeal inflammation. PMID- 1752737 TI - Temporal bone pathology of two infants with Larsen's syndrome. AB - Two infants who had multiple joint dislocations, unusual facies, and bony abnormalities, typical of the syndrome first reported by Larsen et al. (J. Pediatr., 37 (1950) 574-581) are described. This report expands Larsen's syndrome to include the following findings of temporal bone pathology. Case 1 (one year and 8 months old) showed dislocation of the malleus and incus, an abnormal foot plate, mesenchyme remaining in the attic and mesotympanum, poor development of the mastoid air cells, and poor development of the labyrinth. Case 2 (3 years and 6 months old) showed dislocation of the malleus and incus, mesenchyme remaining in the attic and mesotympanum, and an abnormal stapes. These histological findings suggest that a maldevelopment similar to that which occurs in the skeletal system occurs in the temporal bones as well as in the face and extremities including many joints. PMID- 1752738 TI - Complement C4 types in coeliacs and controls. PMID- 1752739 TI - Screening for abnormal eating attitudes in an unselected population of 16 year old Dublin schoolgirls. PMID- 1752740 TI - Aminoglycoside induced ototoxicity in patients with cystic fibrosis. AB - The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels. PMID- 1752741 TI - Cerebral lymphoma and HIV encephalitis in a case of paediatric AIDS, with pre existing multicystic encephalomalacia. AB - A case of intracerebral malignant B cell lymphoma associated with encephalitis typical of Human Immunodeficiency Virus (HIV) infection is described in a 4 year old child, with post-transfusion Acquired Immune Deficiency Syndrome (AIDS) and severe pre-existing cystic encephalomalacia. This report further documents B cell lymphoma as the commonest cause of an intracerebral mass, and an important cause of death in paediatric AIDS. That more than one pathological process may be responsible for neurological symptoms in paediatric AIDS is also emphasised. PMID- 1752742 TI - Broad beam transmission properties of some common shielding materials for use in diagnostic radiology. AB - Broad beam geometry was used to measure the x-ray transmission properties of gypsum wallboard, steel, plate glass, and concrete for x-ray tube potentials of 50-125 kVp using an x-ray generator having a three-phase, twelve-pulse waveform and total initial beam filtration sufficient to provide half-value layers representative of those found in common practice and required by regulatory agencies. Measurement results are presented graphically and as numerical fits to a mathematical model of broad beam transmission to permit their use in the design of protective barriers for medical diagnostic x-ray facilities. PMID- 1752743 TI - Measurement of photon-energy albedo from stratified shielding materials. AB - In the conventional method of measuring photon-energy albedo using a scintillation detector coupled with a multichannel analyzer, tedious efficiency correction by the inverse matrix method was needed. The indigenously designed proportional-response photon counter, with its detection efficiency proportional to energy of incident photons, was used in the present investigation. Use of the proportional-response photon counter makes the measurement straightforward and more accurate. Measurements of energy albedo from stratified layers of aluminum, iron, lead, and concrete using 662-keV and 1250-keV photon energies are reported. PMID- 1752744 TI - Naturally occurring 226Ra concentrations in bone at various ages and alpha doses in adults. AB - Radium-226 concentrations of bone from the fetus and stillborn and from subjects aged 0 to 87 y, especially those older than 15 y, were determined by alpha spectrometry after an ion exchange separation. The median and mean 226Ra concentrations in bone of the adults, 20 to 69 y, were 0.35 and 0.42 Bq (kg bone ash)-1, respectively, and those for ages 15 to 87 y were 0.35 and 0.41 Bq (kg bone ash)-1, respectively. For fetal bones, mean content was 0.29 Bq (kg bone ash)-1. Annual dose equivalents in cells near bone surfaces and active red bone marrow, received from alpha radiation emitted from 226Ra and its decay products in mineral bone, were estimated using the ICRP dosimetric model for bone and assuming masses of source and target tissues for a Japanese Reference Man. PMID- 1752745 TI - Biological dosimetry using the micronucleus assay for lymphocytes: interindividual differences in dose response. AB - The dose response of the number of micronuclei in cytokinesis-blocked lymphocytes after in-vitro irradiation of whole blood with x rays in the dose range 0-4 Gy was studied for a heterogeneous population of 10 donors. One thousand binucleated cells were systematically scored for micronuclei. A linear-quadratic dose dependency of the micronucleus yields was observed. The data were used to derive the accuracy of the dose assessment with the technique in case of a radiation accident. It was shown that for doses of 2 Gy and higher, the uncertainty of the dose was predominantly due to interindividual differences in the x-ray-induced micronucleus yields. At the 95% confidence level, doses lower than 0.3 Gy could not be unequivocally detected with the cytokinesis-blocked micronucleus assay due to the variability of the baseline micronucleus frequency within the donor population and the poor statistical accuracy when scoring 1,000 cells. The precision and sensitivity of the method in the low-dose range could be improved by the knowledge of individual pre-irradiation baseline values and an increase of the number of cells scored by automation of the technique. PMID- 1752746 TI - Evidence of a neutron RBE of 70 (+/- 50) for solid-tumor induction at Hiroshima and Nagasaki and its implications for assessing the effective neutron quality factor. AB - Carcinogenic and genetic effects in the cohort of A-bomb survivors are the main source of information on radiation effects on humans. A detailed analysis of the age-specific mortality rates for solid tumors as a group using the widely accepted linear-quadratic cum cell-killing dose-effect model reveals that the Hiroshima-Nagasaki data are statistically consistent with a limiting, low-dose neutron RBE of about 70. This value, although consistent with a wide range of neutron RBEs, is about 3.5 times higher than the current effective quality factor for neutrons. The data on leukemia mortality do not support the notion of a difference in effectiveness between neutron and gamma radiation; however, these two radiation sources appear to act synergistically. For both types of tumors, the commonly used concepts of constant, dose-independent RBE and "gamma effective dose" cannot be justified other than at very low neutron doses. PMID- 1752747 TI - Suitability of Chinese oil well loggers for an epidemiologic study of the carcinogenic effects of neutrons. AB - Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% less than 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation. PMID- 1752748 TI - Effects of the tissue-air interface in calculations of beta-particle skin dose at a depth of 70 microns. AB - The effects that the tissue-air interface has on the basal-layer dose at a depth of 70 microns from beta emitters on the skin surface are studied using Monte Carlo calculations. The dose is decreased at small lateral distances from a point source but is increased at large distances. PMID- 1752749 TI - Measurements of radioactivity in Jamaican building materials and gamma dose equivalents in a prototype red mud house. AB - Concentrations of 226Ra, 232Th, and 40K measured in bauxite waste, local building materials, and soils are presented and used in model equations to estimate the effective gamma dose-equivalent increments over background in the center of a standard-sized room in a prototype house. Calculated and measured values compare reasonably well. PMID- 1752750 TI - Dose rates for several organs in a human from contaminated soil and hot particles using the QAD computer code. AB - Dose rates from contaminated soil and hot particles have been calculated for several organs of a reference human. The calculation was performed using the computer code QAD-CGGP, a point kernel code employing combinatorial geometry for the representation of the human phantom. QAD uses buildup factors based on the geometric progression form, a buildup factor representation adopted by the American Nuclear Standards Committee. The results indicate that QAD is a powerful and easy-to-run code that produces useful results for practicing health physicists. PMID- 1752751 TI - NTS fallout-induced multiple myeloma in Utah. PMID- 1752752 TI - Incorporating OMT in hospital training. PMID- 1752753 TI - Superlatives and concerns in osteopathic medical education. PMID- 1752754 TI - A genetically engineered protein may hold promise in the fight against the acquired immunodeficiency syndrome (AIDS) PMID- 1752755 TI - Congress has passed a compromise bill requiring healthcare workers who perform invasive procedures be tested regularly for the human immunodeficiency virus (HIV) PMID- 1752756 TI - Undergraduate osteopathic medical education. PMID- 1752757 TI - US osteopathic medical school finances. PMID- 1752758 TI - Osteopathic graduate medical education. AB - Osteopathic graduate medical education is still in transition. The AOA Department of Education will continue to monitor and report on the impact of these changes. PMID- 1752759 TI - AOA continuing medical education. PMID- 1752760 TI - Research programs of the AOA and their role in osteopathic medical education. PMID- 1752761 TI - Evaluating copper and zinc in dairy rations. PMID- 1752762 TI - Serologically atypical canine ehrlichiosis associated with Ehrlichia risticii "infection". PMID- 1752763 TI - Veterinary history. PMID- 1752764 TI - Preparing for disasters. PMID- 1752766 TI - Wills requiring the destruction of pets--the veterinarian's position. PMID- 1752765 TI - How to keep your sanity, self-respect, and dignity in a rural practice. PMID- 1752767 TI - Effect of storage on measurement of ionized calcium and acid-base variables in equine, bovine, ovine, and canine venous blood. AB - The stability of blood ionized calcium (Ca2+) and acid-base variables in equine, bovine, ovine, and canine venous blood samples (n = 15, in each group) stored at 4 C for 3, 6, 9, 24, or 48 hours was studied. Variables included blood Ca2+ and standard ionized calcium (Ca2+ corrected to pH 7.4) concentrations, pH, blood carbon dioxide and oxygen tensions, base excess, bicarbonate concentration, and total carbon dioxide content. Results indicate that storage of blood samples at 4 C for up to 48 hours, despite appreciable acid-base changes, is associated with less than 1.5% change in equine, bovine, and ovine blood Ca2+ concentrations. Similar changes were observed in canine blood during the first 9 hours' storage. After 24 and 48 hours' storage, clinically relevant decrease (10.5 and 15.5%) in canine blood Ca2+ concentration was measured. Therefore, Ca2+ concentration in equine, bovine, and ovine venous blood samples stored up to 48 hours, and in canine blood samples stored up to 9 hours at 4 C is of diagnostic use. PMID- 1752768 TI - Escherichia coli bacteremia associated with hypertrophic osteodystrophy in a dog. AB - Escherichia coli bacteremia was detected in a dog that had hypertrophic osteodystrophy. The dog improved after treatment with cephalothin sodium, iv fluid therapy, and cage rest. The cause of hypertrophic dystrophy has not been determined, although an infectious cause has been suggested. Dogs that are suspected of having hypertrophic osteodystrophy should be monitored closely for evidence of septicemia, and the administration of prophylactic antibiotics may be advisable. PMID- 1752769 TI - Bilateral wedge ostectomy on an 18-month-old llama with severe bilateral carpal valgus. AB - An 18-month-old llama was admitted with severe (45 degrees and 40 degrees) bilateral carpal valgus. The llama had grown normally until it was 6 months old, when the carpal deviations had commenced. Radiography revealed abnormalities at the distal ulnar physes. Premature closure of these physes or abnormal distal ulnar growth may have been the cause of the carpal valgus. The owners requested surgical correction of the condition. Medial wedge osteotomies of each radius were performed 3 weeks apart. Internal fixation of the osteotomized radial bones was accomplished with small right-angled T plates, and the limbs were placed in full-limb casts for 3 weeks and tube casts for 3 more weeks. Both limbs healed in straight alignment, and the llama was able to walk and run normally. Dorsal subluxation of the right radiocarpal joint was noticed after the operation. This was believed to be caused by the uncorrected dorsal bowing of the distal portion of the radius, which had occurred secondary to the severe carpal valgus. PMID- 1752770 TI - Lymphosarcoma with urinary bladder infiltration in a horse. AB - A 9-year-old Thoroughbred mare was examined because of pollakiuria, hematuria, and weight loss of 3 weeks' duration. Physical examination revealed a regular cardiac rhythm with occasional premature contractions, and a soft tissue mass in the pelvic canal palpable per rectum. Microscopic examination of urine sediment revealed numerous RBC and a large population of lymphocytes and lymphoblasts with characteristics of neoplasia. Similar cells were found in peritoneal fluid obtained by abdominocentesis. The horse was euthanatized without treatment. Necropsy revealed a soft tissue mass infiltrating the bladder, vagina, and uterus. Additional masses were found in the sublumbar muscles and myocardium. The histologic diagnosis was lymphosarcoma. PMID- 1752771 TI - Rostral mandibulectomy in five horses. AB - Rostral mandibulectomy with primary gingival closure was performed in 5 horses with rapidly growing or bleeding mandibular tumors. The technique involved preservation of the most caudal portion of the mandibular symphysis to maintain stability. There were no surgical complications or recurrences, and the cosmetic and functional results were good. The histopathologic diagnosis of all the tumors was ossifying fibroma. Rostral mandibulectomy affords a simple and effective technique of treating tumors of the rostral portion of the mandible in horses. PMID- 1752772 TI - Pharmacologic treatment of priapism in two horses. AB - Benztropine mesylate was used successfully to treat priapism that developed during anesthesia in 2 horses. After IV injection, there was a rapid resolution of signs in both horses, and no side effects were observed. The choice of an effective method to treat priapism is challenging because precise causes in most patients have not been well-defined. Benztropine mesylate is a synthetic compound resulting from the combination of the active portions of atropine and diphenhydramine, and is believed effective because of its central acetyl-choline antagonizing properties. PMID- 1752773 TI - Clinical management and surgical repair of atresia coli in calves: 66 cases (1977 1988). AB - The medical records of 66 calves with atresia coli were reviewed; 64 calves were examined at the New York State College of Veterinary Medicine, and 2 calves were examined at the New Bolton Center. In each case, the site of the atresia was within the spiral loop of the ascending colon. In 1 of these calves, a segment of jejunum was also atretic. Absence of feces, progressive weakness, and abdominal distension were the most common clinical signs observed. Other congenital abnormalities were detected in 12 (18%) of 66 calves. Of the 66 calves examined, 5 were euthanatized or died on admission, and 61 had an exploratory celiotomy performed. Eight calves were euthanatized or died during the surgery. In the remaining 53 calves, surgical treatment consisted of enterotomy followed by meconium evacuation, resection of the proximal blind end (in 30 calves), and restoration of intestinal continuity. Restoration of intestinal continuity was done either by side-to-side anastomosis of the proximal to distal blind ends (5 calves), or by side-to-side or end-to-side anastomosis of the proximal blind end to the descending colon (48 calves). Of the 66 calves seen, 27 (41%) were discharged from the hospital, and 11 of these reached reproductive age (11 calves were lost to follow-up before they were 2 years old). From the 11 calves reaching reproductive age, 33 calves were born, one of which may have had atresia coli. The owners should anticipate that long-term survivors likely will have loose feces and normal offspring, but may not grow as well as otherwise expected. PMID- 1752774 TI - Clinical, clinicopathologic, and pathologic features of plague in cats: 119 cases (1977-1988). AB - The clinical, clinicopathologic, and pathologic features of 119 cases of plague in cats from 1977 to 1988 in New Mexico were reviewed. Fifty-three percent were bubonic, 10% were pneumonic, 8% were septicemic, and 29% with neither buboes nor pneumonia were unclassified (but presumed septicemic). Three quarters of the lymphadenopathy was submandibular, and almost half of this was bilateral. One third of all cats had the triad of lethargy, anorexia, and fever in addition to buboes; one quarter had this triad plus abscesses. The overall mortality rate was 33%, with the greatest risk of death in pneumonic cases. For confirmatory diagnosis with a single laboratory test, fluorescent antibody was most frequently used (39% of cases). Cultures and passive hemagluttination titers were also used for confirmation. Gross and histologic findings depended on the type of plague, with Yersinia pestis organisms visualized in buboes of cats with bubonic plague and in the alveolar spaces and respiratory tubules of cats with pneumonic plague. PMID- 1752775 TI - What is your diagnosis? Mummified fetus in the middle portion of the abdomen. PMID- 1752776 TI - Transformation of CD8+ T-cells producing a strong cytopathic effect on CD4+ T cells through syncytium formation by HTLV-II. AB - Human T-cell leukemia virus type II (HTLV-II) is thought to play an important role in the development of CD8+ T-cell malignancies resembling hairy cell leukemia. In this study, dramatic cytopathic effects characterized by syncytium formation in various CD4+ T-cell lines were observed upon their cocultivation with HTLV-II infected T-cells. The HTLV-II infected T-cells, however, did not die as a result of syncytium formation. HTLV-II also transformed CD4+ T-cells and CD8+ T-cells at various coculture ratios. Furthermore, sera from anti-HTLV-II antibody-positive specific carriers inhibited syncytium formation in the CD4+ T cells. These results suggest that HTLV-II infection may contribute to the pathogenesis of associated CD8+ T-cell malignancies. PMID- 1752777 TI - Human granulocyte-macrophage colony-stimulating factor is a growth factor active on human ovarian cancer cells. AB - Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a regulatory glycoprotein that stimulates the production of granulocytes and macrophages from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that recombinant human GM-CSF enhances colony formation by nonhematopoietic human ovarian cancer cell lines, IGROV-1, A2774, ME-180, Pa-1 and A2780. GM-CSF also enhanced the colony formation by cells obtained from fresh ascites of a patient with ovarian mucinous cystadenocarcinoma and a patient with serous papillary ovarian carcinoma. Our observations were made with GM-CSF concentrations between 0.1 to 1 ng/ml; these concentrations are equivalent to the dosages generally used for bone marrow recovery after chemotherapy. PMID- 1752778 TI - Effects of hormones on tumor growth and immunoreactive insulin-like growth factor 1 of estrogen receptor-positive human breast cancer (MCF-7) transplanted in nude mice. AB - The effects of estrogens and tamoxifen were analyzed on estrogen receptor positive human breast cancer (MCF-7) transplanted into athymic nude mice. It was found that (1) the tumor growth and the proportion of 3H-thymidine-labeled cells were significantly increased in the 17 beta-estradiol dipropionate (E2) group, but significantly decreased in the tamoxifen (TAM) group with respect to the control group, and (2) the tumor content of insulin-like growth factor-1 (IGF-1) and the rate of IGF-1-positive cells were significantly lower in the E2 group, but significantly higher in the TAM group than in the control group. It was concluded that the tumor content of IGF-1 and the proportion of IGF-I-positive cells were inversely correlated to the tumor growth and the 3H-thymidine labeling index in vivo. PMID- 1752779 TI - Human tumor-infiltrating lymphocytes transfected with tumor necrosis factor gene could augment cytotoxicity to autologous tumor cells. AB - Human tumor-infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) alpha gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene-transfected TILs exhibited an augmented killing of autologous tumor cells. PMID- 1752780 TI - Induction of renal cell tumors in rats and mice, and enhancement of hepatocellular tumor development in mice after long-term hydroquinone treatment. AB - Hydroquinone (HQ) was administered to F344 rats and B6C3F1 mice of both sexes at a level of 0.8% in the diet for two years. This treatment induced renal tubular hyperplasia as well as adenomas, predominantly in males of both species, and was associated with chronic nephropathy in rats. In addition, the occurrence of epithelial hyperplasia of the renal papilla was increased in male rats. Foci of cellular alteration of the liver were significantly reduced in number by HQ in rats, but in contrast, were increased in mice, where development of hepatocellular adenoma was also enhanced in males. The incidence of squamous cell hyperplasia of the forestomach epithelium was significantly higher in mice of both sexes given HQ than in the controls, but no corresponding increase in tumor development was observed. The present study strongly indicates potential renal carcinogenicity of HQ in male rats and hepatocarcinogenicity in male mice. Thus, it is possible that HQ, which is present in the human environment, may play a role in cancer development in man. PMID- 1752781 TI - Summation effects of uracil and other promoters on epithelial lesion development in the F344 rat urinary bladder initiated by N-butyl-N-(4 hydroxybutyl)nitrosamine. AB - Five non-genotoxic chemicals previously demonstrated to be bladder cancer promoters in 36-week in vivo assays for carcinogenesis were reevaluated in a 20 week experiment in order to assess the summation influence of dietary uracil, a component of RNA, on the development of (pre)neoplastic lesions. The test chemicals, sodium bicarbonate, sodium L-ascorbate, sodium citrate, butylated hydroxytoluene and ethoxyquin, were mixed into the diet at concentrations of 3%, 5%, 5%, 1% and 0.8%, respectively, and administered to male F344 rats after initiation with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks. The test chemicals were given from the 4th to the 8th and the 11th to 20th experimental weeks, uracil being administered at the level of 3% in the diet during the intervening period. Rats in the control group received only BBN and uracil. All animals were killed at week 20 and the bladders were evaluated for the occurrence of putative preneoplastic papillary or nodular (PN) hyperplasia and tumors. Significant increase in the occurrence of PN hyperplasia was observed in all groups initiated with BBN and fed uracil and test chemicals. Quantitative values for papillomas were also significantly increased except in the ethoxyquin-treated group. The results confirm that uracil given in the middle of the post-initiation stage enhances the promoting activity of chemicals and suggest that the use of this chemical might be useful to reduce the duration of current bioassays for bladder chemical carcinogens. PMID- 1752782 TI - Activation and suppression of a cryptic promoter in the intron of the human melanoma-associated ME491 antigen gene. AB - A deletion mutant of the human melanoma-associated ME491 antigen gene starting at the first intron (lambda R31) differentially mediates the antigen expression depending on the cell type. Cryptic promoter activity residing in a 270-base-pair (bp) fragment of the first intron was examined by primer extension analysis and recombinant chloramphenicol acetyltransferase (CAT) assay. The cryptic promoter, further localized within a 153-bp fragment (fr153BN), exerted its effect in Ltk- and H-ras-transformed NIH3T3 (3T3-Hras) but not in parental NIH3T3 cells. The results suggested that the cryptic promoter was associated with a novel ras responsive positive regulatory element, since fr153BN did not contain an AP-1 binding sequence motif, known as the ras-responsive enhancer element. The cryptic promoter activity of fr153BN was suppressed by an upstream 121-bp fragment (fr121SB) which contained a consensus sequence motif for binding of a repressor protein, GC factor, and regions showing sequence similarity with putative cis acting repressor elements found in the vimentin gene. The degree of the suppression was greater in 3T3-Hras than in Ltk- cells. These positive and negative regulatory elements may be differentially involved in the regulation of ME491 antigen expression depending on the cell type. PMID- 1752783 TI - Assessment of new macroscopical classification of gastric malignant lymphoma. AB - We macroscopically classified gastric malignant lymphoma into ST type (submucosal tumor type), non-ST type (non-submucosal tumor type) and Combined type (combination of ST and non-ST type) and assessed this new classification by examining 60 surgically resected cases. Of these, 18 cases (21 lesions) were classified into ST type, 38 cases (54 lesions) into non-ST type and 4 cases (4 lesions) into Combined type. All the large cell, immunoblastic type cases were of ST type and most of the diffuse, small cleaved cell type cases and all the plasmacytoma cases were of non-ST type. Diffuse, large cell type and diffuse, mixed type cases did not seem to be biased toward any of these three macroscopical types. The non-ST type cases frequently showed an infiltrative growth pattern and reactive lymphoid cell hyperplasia adjoining the lesions, while the ST type cases frequently showed an expansive growth pattern without reactive lymphoid cell hyperplasia. The Combined type cases showed both infiltrative and expansive growth patterns in the same lesion. The macroscopical classification defined in this study can be considered useful in determining a range for surgical resection of gastric malignant lymphoma. PMID- 1752784 TI - Prognostic significance of circulating immune complexes in cancer patients. AB - Circulating immune complexes (CIC) were estimated in 100 cancer patients and 25 healthy control volunteers by means of the polyethylene glycol (PEG) precipitation test and latex agglutination inhibition (LAI) test. Pathological levels of CIC were found in 47% of the patients by PEG precipitation test and in 59% of the patients by LAI test; both tests were positive in 33% of the patients. Consequently, the use of the two assays resulted in 73% seropositivity for CIC. The PEG precipitation test detects antigen-antibody complexes formed in the ratio of 2:1 (Ag2Ab), while the LAI test could detect immune complexes formed over an extended range of antigen-antibody ratio including complexes as small as 8S. CIC values were significantly higher by combined assays (P less than 0.001) as compared to individual assays (P less than 0.01) when compared with the control group. It was found that 75% of post-operative follow-up patients became seronegative for CIC in the combined assays, whereas the 25% of post-operative patients who remained seropositive for CIC showed recurrence within three months after surgery. Immune-complex deposition was demonstrated on malignant cells in vitro by direct immunofluorescence studies in 73.3% of patients, while 60% of patients revealed complement-fixing antigen-antibody complexes. It was found that 20% of patients showing positive immunofluorescence with anti-C3-antisera had decreased levels of CIC. Complement-mediated cytotoxic injury results in reduction of tumor cell mass and subsequent decrease in CIC. Necrotizing and leucocytoclastic vasculitis in the tumor mass was initiated by raised CIC levels in vivo in 71% of patients. Necrosis of malignant tumors was seen in 58% of patients, and hemorrhage in 36% of patients. These changes were considered to be an aftermath of immuno-complex vasculitis initiated by CIC. PMID- 1752785 TI - Antitumor effector mechanism of interleukin-1 beta at a distant site in the double grafted tumor system. AB - Recombinant human interleukin-1 beta (IL-1 beta) inhibited the growth of not only the right, but also the left non-treated tumor in a double grafted tumor system. Since the antitumor activity of IL-1 beta against the right and left tumors was not seen in nude mice, lymphocytes have a key role in the antitumor effect of intratumoral administration of IL-1 beta. TIL (tumor-infiltrating leukocytes) obtained from left and right side tumors treated with IL-1 beta were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from the right side clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. Spleen cells and right and left regional lymph node cells prepared from IL-1-treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1-positive lymphocytes increased in the spleen and in the right regional lymph nodes after intratumoral administration of IL-1. Isolated tumor cells obtained from the right tumor treated with IL-1 beta and the left side tumor on day 6 were cultured in RPMI 1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor and macrophage chemotactic factor activities were detected in the culture media from IL-1-treated tumor tissues cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated tumor tissues. These results suggest that intratumoral administration of IL-1 first induces neutrophils and macrophages in the right tumor, then Lyt-1-positive cells in the right regional lymph nodes and in the spleen, and subsequently induces macrophages in the left, non-treated tumor. PMID- 1752786 TI - Murine tumor cells metastasizing selectively in the liver: ability to produce hepatocyte-activating cytokines interleukin-1 and/or -6. AB - Increasing evidence suggests that an intimate correlation may exist between the production of a cytokine, granulocyte-macrophage colony-stimulating factor (GM CSF) and the ability to metastasize spontaneously in the lungs in murine transplantable tumors. In the present study, we further examined the cytokine production by tumor cells with the ability to metastasize in the liver. Four out of 8 test tumors, which produced metastasis in the lungs but not in the liver, exhibited the ability to produce GM-CSF activity in culture. Three other tumors produced metastasis in the liver but not in the lungs. These tumor cells exhibited no ability to produce GM-CSF, but two of them expressed an interleukin 6 (IL-6) mRNA and also produced IL-6 activity in the culture fluids. One of the two IL-6-producing tumors and the remaining liver metastatic tumor produced interleukin-1 (IL-1) as revealed by bioassay and neutralization test. In the tumor cells producing pulmonary metastasis, neither IL-6 gene expression nor IL-1 production could be detected. The last test tumor, which produced no metastasis either in the lungs or liver, produced neither GM-CSF, IL-1 nor IL-6. Furthermore, injection of antisera reactive to recombinant murine IL-6 caused a marked decrease of the number of liver metastases of an IL-6-producing tumor, but not lung metastases of a GM-CSF-producing tumor, which could be markedly inhibited by injection of anti-recombinant murine GM-CSF sera. These results suggest the possibility that there may be a correlation between the cytokines produced by tumor cells and their organ specificity in spontaneous metastasis, and also indicate that these tumor models may provide a useful tool for studies on the role of cytokines in tumor metastasis. PMID- 1752787 TI - Fluctuations in tumor blood flow under normotension and the effect of angiotensin II-induced hypertension. AB - To elucidate the significance of angiotensin II (AII)-induced hypertension chemotherapy, changes of tissue blood flow both in normal subcutis and in tumors (AH109A, LY80) were measured with the hydrogen gas clearance method. A newly developed anesthetic machine was used to keep the animals' condition constant. Tissue blood flow in normal subcutis and tumors always fluctuated with time under normotension. The nature and the rate of fluctuation in tumor blood flow were almost identical in two different types of tumors. However, the fluctuation of blood flow in tumor and that in normal subcutis were almost always inversely related when blood flows in these different tissues were measured simultaneously, i.e., when tissue blood flow in normal subcutis decreased, tumor blood flow increased, and vice versa. The findings supported the idea that the connection mode between the tumor vascular bed and normal vascular bed is a parallel circuit. Vascular resistance in the normal vascular bed under AII-induced hypertension seemed to be greater than that under normotension, because the AII increased tumor blood flow always exceeded the maximum tumor blood flow under normotension. Due to the fluctuations of tumor blood flow, no-flow or low-flow areas, resistant to delivery of anti-cancer drugs, moved sporadically within the tumor under the normotensive condition. However, good conditions for drug delivery to tumor tissue were induced by AII-induced hypertension. PMID- 1752788 TI - Antitumor activity and metabolism of a new anthracycline-containing fluorine (ME2303) in Lewis lung carcinoma-bearing mice. AB - (7-O-(2,6-Dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone-14- hemipimerate (ME2303) showed a more marked growth inhibition of Lewis lung carcinoma than adriamycin (ADM). When administered to s.c. Lewis lung carcinoma-bearing mice, ME2303 in the plasma and liver was rapidly metabolized and disappeared. However, ME2303 was incorporated into the tumor at higher concentrations and remained in the tumor for a longer period than in the plasma and liver. ME2303 was metabolized to 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone (M1), the product of esterolysis, and its reduced derivative at the C-13 position (M2). Larger amounts of these metabolites were found in the analyzed tissues than in plasma. The maximum concentration of M1 in the tumor was observed at 2 h posttreatment, while the maxima in the plasma and liver were observed at 15 min. On the other hand, i.v. injection of M1 into mice showed a weaker antitumor effect than ME2303 injection, though M1 levels in the plasma and tumor were almost the same as those after administration of ME2303 at the maximum tolerated doses. Some metabolites of ME2303 were found in the tumor after administration of ME2303, but not after administration of M1. ADM remained in the analyzed tissues for a long period and ADM concentrations in the tumor were much higher than in the plasma but less than in the liver. M1 reached a concentration higher than that of ADM in the tumor, opposite to the pattern observed in the liver. The conversion process from ME2303 to M1, the metabolites and their locations in the tumor may be important for the marked antitumor effect of ME2303 in vivo. PMID- 1752789 TI - The influence of intra-arterial infusion of arginine vasopressin on cochlear blood flow in the rat. AB - Intra-arterially infused arginine vasopressin (AVP) elevated systemic blood pressure (BP) in the Sprague-Dawley rat according to a dose-response pattern while cochlear blood flow (CoBF), as measured by laser Doppler flowmetry, was elevated only at the highest dose. Skin blood flow (SBF) decreased significantly with AVP infusion. The local infusion of AVP into the anterior inferior cerebellar artery (AICA), which supplies the common cochlear artery, produced significant dose-dependent reductions in CoBF with no changes in systemic blood pressure. Pretreatment of the local cochlear supplying vessels with an AVP specific V1 receptor antagonist attenuated subsequent AVP-induced decreases in CoBF, thereby demonstrating specificity of the response. These results suggest that CoBF is reasonably stable in response to systemic AVP infusion until blood pressure exceeds an elevation from base level of approximately +60 mm Hg. One of the mechanisms responsible for this autoregulatory response may be vasoconstriction mediated by the interaction of vasoactive peptides such as AVP and its receptors located in the vasculature of the inner ear or in the more peripheral vessels directly supplying the cochlea. PMID- 1752790 TI - Objective auditory threshold estimation using sine-wave derived responses. AB - A derived response method of acquiring frequency specific auditory evoked potentials that utilizes a pure tone in combination with a toneburst is applied to the measurement of hearing sensitivity in guinea pigs, chinchillas and pocket gophers. Two experiments which demonstrate that thresholds acquired via tone derived responses are 10 to 15 dB more sensitive than thresholds to solitary tonebursts are described. The derived potentials approximate behaviorally acquired thresholds at frequencies of 0.5 kHz and above. This technique may provide a more rapid means of assessing hearing sensitivity in laboratory animals than by behavioral means. PMID- 1752791 TI - Shared-stimulus driving and connectivity in groups of neurons in the dorsal cochlear nucleus. AB - Extracellular spike discharges were recorded from ensembles of up to five neurons simultaneously in the DCN of guinea pig using solid-state, thin-film, multichannel electrodes having up to five recording sites spanning up to 600 microns. Responses from 73 unit pairs were collected of which 54 had both units responding to pseudorandom wideband noise stimulation. Shared-stimulus driving was present in 78% (42/54) of the unit pairs and could be attributed to an overlap in their spectral sensitivities. Effective connectivity was indicated for 87% (47/54) of the unit pairs. Wideband noise proved more useful than tonebursts for investigating shared-stimulus driving and connectivity because it evoked widespread, but not overly synchronous, responses in the ensembles. PMID- 1752792 TI - Coding of interaural time differences of transients in auditory cortex of Rattus norvegicus: implications for the evolution of mammalian sound localization. AB - We obtained quantitative evidence on the coding of interaural time differences (ITDs) of click stimuli by 40 single neurons in the auditory cortex of anesthetized albino rats. Most of the neurons (31/40) received an excitatory input from the contralateral ear, and an inhibitory input from the ipsilateral ear (EI cells). These neurons expressed their sensitivity to ITDs in a sigmoidal relation between spike count and ITD, with maximal responses associated with contralateral-leading ITDs. The mean ITD dynamic range was 590 microseconds. The dynamic ranges typically encompassed at least part of the behaviorally-relevant range (about +/- 130 microseconds). Variations in ITD from 130 microseconds favoring one ear to 130 microseconds favoring the other ear caused spike response rate changes, on average, of 29.5%. These data are similar to those previously presented for the central auditory systems of larger mammals, whose auditory localization acuity is significantly better than that of the rat. We argue, therefore, that the sound localization mechanisms based on transient ITDs have not evolved in a fashion that covaries with interaural distance, and that there exists a mismatch between the ITDs the rat will encounter in the free field, and the ITDs which are encoded by its nervous system. This may be one reason why sound localization acuity has a roughly inverse relation to interaural distance. PMID- 1752793 TI - Postnatal developmental changes in inner ear ornithine decarboxylase (ODC). AB - Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, is important in cellular growth, differentiation and development. Although ODC has been quantitated in cochlear tissues of the adult rat, it has not been assessed quantitatively in developing inner-ear tissues. The purpose of the present study was to quantitate ODC in cochlear tissues of the rat during the period of development of hearing. Cochlear ODC was significantly elevated throughout the period of cochlear maturation in that it increased rapidly during the first 10 days, peaked on day 10 and then declined thereafter. ODC in the lateral wall/organ of Corti tissues was significantly higher than in the cochlear nerve in developing, but not in adult rats. Further examination of separate cochlear tissues from 10-day old rats revealed that ODC activity was higher in the organ of Corti than in the lateral wall or cochlear nerve. Postnatal changes in ODC paralleled functional maturation of hearing and the hypersensitive period for aminoglycoside ototoxicity in the rat. Since aminoglycosides have been shown to inhibit ODC in vitro, aminoglycoside inhibition of polyamine synthesis may mediate the hypersensitivity of developing animals to the effects of these drugs. PMID- 1752794 TI - Rate-versus-level functions of primary auditory nerve fibres: evidence for square law behaviour of all fibre categories in the guinea pig. AB - Detailed measurements of rate-versus-level (RI) functions close to threshold were made from single primary auditory nerve fibres in the guinea pig cochlea. For all fibres, a simple square law provided the best statistical fit to the data near threshold, regardless of spontaneous fibrin rate of the fibre. In no case was a better fit obtained with an exponent greater than 2. We conclude that a simple square law is an accurate description of the underlying synaptic drive to all primary auditory nerve fibres. For fibres with very low spontaneous firing rates the best square law fit near threshold frequently led to the formal mathematical estimate of a negative firing rate as the asymptotic value of the spontaneous firing rate. The 'negative spontaneous rate' of low spontaneous rate fibres derived from curve fitting can be conceptualized by postulating that for sound pressures well below threshold in these fibres the underlying synaptic drive lies below a threshold value at a site determining action potential generation. PMID- 1752795 TI - Turn-specific and pigment-dependent differences in the stria vascularis of normal and gentamicin-treated albino and pigmented guinea pigs. AB - The aims of the present study were to determine which structures in the stria vascularis (SV) may depend upon the presence of pigmented melanocytes both for normal morphology and for the expression of gentamicin ototoxicity in the inner ear. These pigment-dependent influences were inferred through comparisons of the SV in pigmented guinea pigs and in albinos containing nonpigmented melanocytes. Results were obtained from 6 albino and 8 pigmented guinea pigs given gentamicin, and from 3 albino and 3 pigmented control animals not receiving the drug. One month old animals received gentamicin daily (100 mg/kg) for 14 days and recovered for an additional 14 days before being prepared for electron microscopy. The SV from each of the 4 cochlear turns was analyzed using stereological point counting procedures. In control animals, differences were found in the higher cochlear turns, where volume density for the marginal cells in albinos was abnormally large (turns 3 and 4), while the volume density for intermediate cells (melanocytes) was abnormally small (turn 3). Cell volume estimates for the intermediate cells were significantly smaller in the albino than pigmented control animals in the higher cochlear turns, indicating that functional abnormalities may be found in the albino cochlea. In animals exposed to gentamicin, marginal cell volume density was reduced significantly in turn 4 of albinos, but not in any region of the pigmented inner ears. Radial area of SV and estimates of the absolute volumes for marginal cells in albinos given gentamicin also were significantly reduced in turn 1 compared to their controls; such differences were not observed in the pigmented animals. The results indicate that marginal cell size is significantly reduced in albino but not pigmented animals 14 days after gentamicin exposure, and further suggest a role of pigmented melanocytes in ameliorating gentamicin-induced cochlear damage. PMID- 1752796 TI - The development of frequency representation in the inferior colliculus of the kitten. AB - While morphologically the kitten's cochlea matures first at the basal or high frequency region, behavioural and physiological evidence suggests that it responds first to low-frequency sound. Explanations of this paradox include the suggestion that the spatial representation of frequency within the cochlea changes as a function of age. We have used the [14C]-2-deoxyglucose technique to study the development of frequency representation in the central auditory system of the kitten. We report here that while the locations within the inferior colliculus (IC) where high- and mid-frequency sounds are represented shift markedly between 10 and 35 days of age, the location where low-frequency sound is represented does not alter. The IC representation of low frequencies is adult like by 10 days of age but that of higher frequencies continues to mature until as many as 35 days. Despite its morphological immaturity with respect to other regions, the apex of the cochlea appears to be the first region to become tuned to those frequencies to which it is tuned in the adult. We found little labelling at 5 and 7 days of age to 75-80 dB stimuli, but it is quite possible that the high-frequency region might respond to very intense low frequencies before 10 days of age. to very intense low frequencies before 10 days of age. PMID- 1752797 TI - Postnatal maturation of spiral ganglion neurons: a horseradish peroxidase study. AB - Using an in vitro cochlear preparation from postnatal hamsters, spiral ganglion cells (SGCs) were labeled retrogradely following extracellular injections of HRP into the cochlear nerve. In 24 cochleae from hamsters between postnatal days (P) 0 and 10, the neuronal morphology of 201 SGCs and their peripheral axons were analyzed. From P 0 to 3, labeled SGCs had few distinguishable features. Although SGCs could be traced separately to inner hair cells (IHCs) and outer hair cells (OHCs), they all had roughly bipolar-shaped cell bodies. Approximately half of the labeled SGCs had peripheral axons that spiraled some distance before entering radial fiber bundles. From P 3 to 7, SGCs increased in size by nearly 30% and the number of SGCs with spiraling peripheral axons decreased to near zero. At P 10, the central axon diameter to peripheral axon diameter ratios distinguished two populations of SGCs. The hair-cell innervation patterns of SGCs also changed morphologically as a function of postnatal age. At P 0, radial fiber (RF) terminals of peripheral axons contacted as many as 8 IHCs; by P 3, RFs contacted typically one or two IHCs. The terminal portions of peripheral axons contacting OHCs did not show any appreciable spiral until P 2. By P 5, individual outer spiral fibers (OSFs) had greater spiral lengths underneath row-3 OHCs and the number of OHC contacts was also greatest for row-3 OSFs. These data suggest that SGCs undergo a systematic maturational process. Furthermore, the morphological differentiation of SGCs occurs after they have established separate inner and outer hair cell innervations. PMID- 1752798 TI - Effect of high-frequency hearing loss on compound action potentials recorded from the intracranial portion of the human eighth nerve. AB - Compound action potentials (CAP) were recorded from the exposed intracranial portion of the eighth nerve to stimulation with click sounds in patients with sensorineural high-frequency hearing loss who underwent microvascular decompression (MVD) operations to treat trigeminal neuralgia (TN). In patients with normal hearing the CAP recorded in that way is characterized by a negative peak, preceded by a small positivity and followed by a positivity and sometimes a second negative peak. In patients with high-frequency hearing loss the CAP also usually had an initial sharp negative peak in response to clicks of high intensity (105 to 110 dB Pe SPL), similar to findings in patients with normal hearing, but in patients with high-frequency hearing loss the initial negative peak was often followed by a slow negative deflection. The latency of the initial negative peak in the CAP in patients with high-frequency hearing loss was longer than the latency of this peak in patients with normal hearing, but the difference in latencies of this peak to condensation and rarefaction clicks was small. When the stimulus intensity was lowered the amplitude of the initial peak decreased, and the CAP became dominated by a broad negative peak with a latency of 6 to 8 ms. In 11 of 15 patients with severe high-frequency hearing loss, a series of quasi-periodic waves was superimposed on the CAP. The frequency of these waves varied between 500 and 1200 Hz, and the waves could be detected between 6 and 16 ms after presentation of the click stimulus. These waves were usually present in the response to stimuli in the intensity range from 75 to 110 dB Pe SPL. Only 4 of 17 patients with normal hearing had similar waves. PMID- 1752799 TI - Hypoxia induced hearing loss in animal models of the fetus in-utero. AB - The human fetus in-utero has low arterial oxygen tension. It has, therefore, been suggested that at greater than 28 weeks gestational age, the fetus may have a sensori-neural hearing loss comparable to that seen in adult cats exposed to similar degrees of hypoxia. This is due to hypoxia induced depression of the endocochlear potential. However, fetal blood is provided with compensatory mechanisms (elevated hematocrit and hemoglobin and special fetal hemoglobin) which enable pick up and transport of more oxygen from the placenta than adult blood under the same physiological conditions. Therefore, the hypothesis of a fetal sensori-neural hearing loss due to oxygen lack was tested in the following animal models: a) Adult cats to which feline red blood cells were infused thus causing a polycythemia similar to fetal conditions; b) Adult rats acclimated to altitude in a hypobaric chamber, inducing erythropoiesis with elevated hematocrit and hemoglobin; c) Neonatal guinea pigs and goats studied when they were less than 12 hours old so that the fetal compensatory mechanisms were still present. In each model, hypoxia (PaO2 20-30 mmHg) induced an ABR threshold elevation resembling that obtained in the uncompensated adult animal. Thus these experiments seem to have confirmed the hypothesis of a fetal, hypoxic induced sensori-neural hearing loss even though such experiments have not been conducted directly on fetal animals. PMID- 1752800 TI - Course and distribution of efferent fibers in the cochlea of the mouse. AB - The course, distribution and termination of single efferent fibers to the cochlea has been described in only a few animals and relatively few fibers have been studied with knowledge of their ipsilateral or contralateral origin. In order to examine the efferent fibers in the mouse, the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was iontophoretically injected into one side of the brain stem near the location of known efferent nuclei. Examination of surface preparations of the cochlea revealed detailed information for both the lateral olivocochlear (LOC) and medial olivocochlear (MOC) systems. Many, but not all, fibers entered the cochlea within the intraganglionic spiral bundle (IGSB). The LOC fibers were restricted to the ipsilateral cochlea and rarely branched within the IGSB and osseous spiral lamina (OSL). In the organ of Corti, they traveled either basally or apically in the region of the inner hair cells (IHCs), spanning lengths up to 130 microns (basally) and 890 microns (apically). Terminal swellings of these fibers were ca 3.0 microns in diameter. Numerous en passant swellings were present where the fibers formed a plexus in the area of the IHCs. The MOC fibers followed a similar course in the IGSB and OSL, and within the OSL the fibers had few branches. Within the organ of Corti they traveled apically (up to 70 microns) in the nerve bundles located in the IHC area before they crossed the tunnel of Corti. In the region of the OHCs, 9% of the traceable fibers branched to innervate two to three OHCs while 91% appeared to innervate only one OHC. There was no discernible difference in the distribution of contralateral and ipsilateral MOC projections in terms of cochlear region or outer hair cell rows. PMID- 1752801 TI - The effect of estradiol, trenbolone acetate, or zeranol on growth rate, mammary development, carcass traits, and plasma estradiol concentrations of beef heifers. AB - The effect of a single implantation (on d 1) with one or two long-acting, biodegradable estradiol implants (1E or 2E) on plasma estradiol concentrations in beef heifers was determined. The growth rates of these (2E) heifers, and of heifers repeatedly implanted with trenbolone acetate (TBA) or zeranol (Z) on d 1, 84, 168, and 252 of the trial, were compared to growth rates of controls. Trenbolone acetate alone was compared to TBA + 2E, and 2E was compared to 1E. At a mean age of 84 d (d 1 of experiment), 81 Hereford x Friesian heifers were allocated at random to the following treatments: Control (n = 15); TBA (n = 15); 1E (n = 12); 2E (n = 15); Z (n = 13); or TBA + 2E (n = 11). Mean live weight (kg) prior to slaughter on d 368 and hot carcass weight (kg) for heifers assigned to treatment Groups 1 to 6, respectively, were 366 and 200, 391 and 212, 374 and 201, 386 and 207, 387 and 210, and 391 and 208 (residual SD = 30.3 and 20.2). Heifers assigned to both the 2E and Z treatments were heavier on d 368 (P less than .05) and had longer teats on d 279 (P less than .05), less pelvic fat (P less than .05), and heavier kidneys (P less than .005) than control heifers. Heifers assigned to the TBA treatment had shorter teats on d 279 (P less than .001) but greater final live weight (P less than .05) and carcass weight than control heifers. Heifers given TBA alone had more pelvic fat (P less than .05) and lighter kidneys (P less than .05) than those given TBA + 2E. Mean estradiol concentrations in both the ipsilateral and contralateral jugular veins of heifers assigned to the 2E and TBA + 2E treatments, and in the ipsilateral jugular veins of heifers given 1E, were greater (P less than .05) than those in control heifers; concentrations did not decline during the experiment. PMID- 1752802 TI - Mastitis in beef cows and its effects on calf weight gain. AB - Quarter milk samples from 51 purebred (Angus, Polled Hereford, and Simmental) and 69 crossbred (Angus x Simmental x Charolais three-way cross) beef cows were collected aseptically at three times during lactation to determine the prevalence of intramammary infection, milk somatic cell counts (SCC), and effects of infection on calf weight gain. Quarter infection prevalence was 13.1, 14.9, and 27.5% in early, mid, and late lactation; corresponding cow infection prevalence was 25.8, 29.2, and 54.4%. Staphylococcus aureus was isolated from 2.9, 2.7, and 3.2% of quarters in early, mid, and late lactation, respectively. Corynebacterium bovis, generally regarded as a minor pathogen, was isolated from 4.0, 7.6, and 18.2% of quarters at the three respective times. Geometric SCC means (10(3) cells/ml) were 1,522, 344, and 509 for S. aureus-infected quarters; 344, 899, and 221 for Staphylococcus hyicus-infected quarters; 65, 36, and 86 for C. bovis infected quarters; and 20, 17, and 18 for uninfected quarters in early, mid, and late lactation, respectively. Adjusted 205-d weight gain for calves with S. aureus-infected dams was 9.6 kg less (P less than .05) than for calves with uninfected dams. Adjusted 205-d weight gain for calves with dams infected with any mastitis pathogen did not differ significantly from that of calves with uninfected dams. At weaning half of the infected cows and half of the uninfected cows were given an intramammary infusion product containing 300 mg of cephapirin benzathine in each quarter; the remaining cows were untreated controls. Quarter samples were collected aseptically from all cows 14 to 28 d after subsequent calving. Quarter prevalence of infection after calving was lower (P less than .05) in treated (8.2%) than in control (22.4%) cows. Significantly more infections present at weaning were eliminated in treated than in control cows, but the new infection rate during the dry period and early lactation did not differ between the two groups. PMID- 1752803 TI - Effect of supplemental lysocellin and tetronasin on growth, ruminal and blood metabolites, and ruminal proteolytic activity in steers grazing ryegrass. AB - Forty-eight Angus and Brangus steers (249 kg initial BW) were used in a randomized complete block design. Steers grazed annual ryegrass (Lolium multiflorum [L.] Lam.) for 107 d and were sampled at 35 and 70 d. Treatments consisted of a corn supplement (C) or corn supplement plus either 80 mg.steer-1.d 1 of lysocellin (L) or 60 mg.steer-1.d-1 of tetronasin (T). When compared with C, ADG of L- and T-fed steers was higher (P less than .05) for the complete 107-d study (1.15 vs 1.25 kg/d). At 35 d, ruminal acetate:propionate ratio tended (P = .07) to be higher for C than for L- and T-fed steers (4.6 vs 3.8). When compared with T, steers fed L tended (P = .11) to have higher acetate:propionate ratios. Ruminal concentrations of ammonia and free amino acids were not affected (P greater than .05) by treatment, but ruminal proteolytic activity tended (P = .13) to be lower for L- and T-fed than for C steers at 70 d. Ionophores did not alter (P greater than .05) ruminal mineral concentrations, but ruminal Mg concentration tended (P = .14) to be higher for T- than for L-fed steers at 70 d. When compared with L- and T-fed steers, C steers had lower (P less than .05) plasma concentrations of Mg (23.7 vs 21.9 mg/liter) and Ca (113.0 vs 104.2 mg/liter) at 35 d. Plasma mineral concentrations were similar (P greater than .05) for L- and T-fed steers. Data are interpreted to indicate that L and T may improve ADG, decrease ruminal acetate:propionate ratio, and alter mineral metabolism. PMID- 1752804 TI - Production from first-calf beef heifers fed a maintenance or low level of prepartum nutrition and ruminally undegradable or degradable protein postpartum. AB - Two experiments were conducted in consecutive years to determine the effects of prepartum nutrient level and postpartum ruminally undegraded protein intake on nutrient status, milk production, subsequent calf production, and reproductive performance of 126 crossbred, primiparous beef heifers. Prepartum treatments were low nutrient intake (LN) (approximately 2.5 kg of TDN, .5 kg of CP animal-1.d-1 and maintenance nutrient intake (MN) (5 kg of TDN, 1 kg of CP animal-1.d-1), which were fed for 75 d before parturition. Two postpartum protein supplements were formulated to provide 250 g/d of ruminally degradable protein (RD) and one to supply ruminally undegraded protein (UD) at 250 g/d of additional UD CP compared to the RD supplement. Cholesterol was lower (P less than .01) in heifers given UD than in heifers given RD. Blood urea nitrogen was higher (P less than .01) for UD-fed heifers than for RD-fed heifers and was higher in LN heifers (P less than .06) than in MN heifers. Milk production did not differ (P greater than .11) as a result of LN, MN, UD, or RD. Postpartum cow weight gain was greatest (P less than .01) for UD and LN heifers. The percentage of heifers bred during the first estrous cycle of the breeding season was greater (P less than .02) for UD than for RD. Overall, prepartum nutrition did not interact with postpartum protein supplement, nor did it have any effect on postpartum interval, whereas UD increased cow weight gain postpartum and reduced postpartum interval. PMID- 1752805 TI - The effects of recombinant porcine somatotropin on reproductive function in gilts treated during the finishing phase. AB - The objective of this study was to determine the effects of recombinant porcine somatotropin (rpST) treatment during the finishing phase on subsequent reproductive function in crossbred gilts. Forty gilts weighing 50 kg and housed in a swine finishing facility were randomly assigned to control or rpST treatment. Four control and four rpST-treated gilts were allotted per pen. Twenty rpST-treated gilts received 6 mg of rpST.gilt-1.d-1 in 1 ml of buffered carrier and 20 control gilts received 1 ml of buffered carrier.gilt-1.d-1. Injections were administered daily at 1400 in the extensor muscle of the neck. All gilts received an 18% CP diet containing 1.2% lysine. Treatment was terminated when the average weight in each pen reached 110 kg. Gilts treated with rpST gained more weight (P less than .05) than control gilts (59.8 +/- 1.0 vs 53.5 +/- 1.0 kg). Age at puberty was not different (rpST, 182.2 +/- 3.3; control 181.4 +/- 3.1 d). Prior treatment with rpST did not significantly affect length of estrus (rpST, 1.9 +/- .1; control, 1.8 +/- .1 d) or estrous cycle length (rpST, 20.6 +/- .4; control, 20.4 +/- .4 d). Ovulation rates at second estrus were similar for rpST gilts (15.1 +/- .5) and control gilts (14.4 +/- .5). More embryos (P = .10) were recovered on d 9 to 12 of gestation from rpST-treated gilts than from control gilts (13.1 +/- .9 vs 10.7 +/- .9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752806 TI - Effect of selection for litter size and body weight on hormone-induced ovulation rate in mice. AB - Genetic differences in natural vs hormone-induced ovulation rates were compared in immature female mice from five lines that had undergone long-term single-trait and antagonistic index selection for litter size and(or) 6-wk BW. Lines used were control (K); high litter size (L+); high BW (W+); low litter size and high BW (L W+); and high litter size and low BW (L+W-). Natural ovulation rate at a mean age of 34.3 d and hormone-induced (5 IU of pregnant mare's serum gonadotropin followed 2 d later by 5 IU of human chorionic gonadotropin) superovulation rate at a fixed age of 31 d were obtained. Total number of eggs ovulated was affected by line (P less than .001), treatment (P less than .001), and line x treatment interaction (P less than .001). Line differences were subsequently tested within treatment because of the significant line x treatment interaction. Line differences were important (P less than .001) for natural ovulation, hormone induced ovulation, and response to hormones. Mean natural ovulation rates for K, L+, W+, L-W+, and L+W- were 14.1, 19.8, 15.1, 13.6, and 16.4, respectively. Selection changed ovulation rate by 40, 16, 7, and -4% in the L+, L+W-, W+ and L W+ lines, respectively (P less than .01). Hormone-induced ovulation rates in K, L+, W+, L-W+, and L+W- were 32.3, 24.6, 19.6, 20.9, and 22.1, respectively. Exogenous hormones increased ovulation by 18.2, 4.8, 4.6, 7.3, and 5.7 ova for K, L+, W+, L-W+, and L+W-, respectively (P less than .001). Lines with lower natural ovulation rates had higher responses to superovulation. Increased ovulation rate due to treatment ranged from 24.3% in L+ to 129% in K. These results indicate significant differences among lines in ovarian response to exogenous hormones. PMID- 1752807 TI - A deterministic computer simulation model of life-cycle lamb and wool production. AB - A deterministic mathematical computer model was developed to simulate effects on life-cycle efficiency of lamb and wool production from genetic improvement of performance traits under alternative management systems. Genetic input parameters can be varied for age at puberty, length of anestrus, fertility, precocity of fertility, number born, milk yield, mortality, growth rate, body fat, and wool growth. Management options include mating systems, lambing intervals, feeding levels, creep feeding, weaning age, marketing age or weight, and culling policy. Simulated growth of animals is linear from birth to inflection point, then slows asymptotically to specified mature empty BW and fat content when nutrition is not limiting. The ME intake requirement to maintain normal condition is calculated daily or weekly for maintenance, protein and fat deposition, wool growth, gestation, and lactation. Simulated feed intake is the minimum of availability, DM physical limit, or ME physiological limit. Tissue catabolism occurs when intake is below the requirement for essential functions. Mortality increases when BW is depressed. Equations developed for calculations of biological functions were validated with published and unpublished experimental data. Lifetime totals are accumulated for TDN, DM, and protein intake and for market lamb equivalent output values of empty body or carcass lean and wool from both lambs and ewes. These measures of efficiency for combinations of genetic, management, and marketing variables can provide the relative economic weighting of traits needed to derive optimal criteria for genetic selection among and within breeds under defined industry production systems. PMID- 1752808 TI - Simulation of life-cycle efficiency of lamb and wool production for genetic levels of component traits and alternative management options. AB - A deterministic computer model was used to predict effects of genetic improvements in performance and of management options on life-cycle flock TDN input per unit of empty body weight (EBW) or carcass lean (CLN) equivalent value of market lamb, cull ewe, and wool output from a pure breeding system of sheep production for sheep fed to maintain normal weight. Relative values per kilogram for market lambs, cull ewes, and clean wool were 1 to .33 to 2.04 in lamb empty body equivalent, but 1 to .33 to 1 in lamb carcass lean equivalent. A 10% increase in lamb viability improved TDN/EBW or CLN by -15 to -20% for high to low lambing rates. Corresponding smaller gains were -7 to -11% for fertility, -3 to 13% for lambing rate, -1 to -3% for wool growth rate, -1 to -5% for milk production without creep feeding, -2 to -1% for mature size to about 70 kg, and .6 to -.9% for precocity of fertility. Increasing leanness 10% improved TDN/CLN by -3 to -1% but increased TDN/EBW 3% because of higher maintenance requirements of leaner sheep. Higher protein requirements for increased lambing rate, milk production or leanness, or greater increases in non-feed than in feed costs, would mean only slightly less reduction of TDN/output than shown. Creep feeding was beneficial only for prolific, low-milking stock. Flushing reduced adverse effects of restricted feeding. Different values for wool vs meat or for costs of feed vs non-feed inputs would change results. These estimates for relative economic importance of traits apply to derivation of optimum criteria for selection among breeds or crosses, or within-breeds used in rotation crossbreeding, but would differ for specialized terminal-sire or maternal breed roles. PMID- 1752809 TI - Simulated effects of reproductive performance on life-cycle efficiency of lamb and wool production at three lambing intervals. AB - A deterministic computer model of a purebreeding sheep production system was used to simulate effects on life-cycle efficiency from genetic changes in lambing rate (LB), fertility (FERT), precocity of fertility (PREC), and estrus season length (ES) under annual (Y), 4-mo (A), and 73-d (S) breeding intervals. Ewes and lambs of a 1,000-ewe flock were fed to requirement through five yr, beginning with ewe lambs at the optimal breeding season and accumulating feed input (TDN) and market lamb equivalent weight of output (EBW), including cull ewes and wool. For annual lambing, improvement in cost (TDN/EBW equivalence) per 10% increase in genetic potential was -9.8, -8.2, -1.3, and -.8% for LB, FERT, PREC, and ES, respectively. For the A and S lambing intervals, corresponding gains in TDN efficiency were -19 for FERT and -9% for LB when ES was 72 d, but only -6 and -5% when ES was 192 d. Increasing PREC by 10% improved cost -3% under accelerated systems when ES was 72 d, but less than -1% when ES was 192 d. Cost reduction from 10% longer ES under A and S breeding intervals was greater when other reproductive performance was low (-11 and -17%) rather than high (-2 and -3%). Reduction in costs for A and S vs Y lambing intervals was greatest with long ES and was greater with low (-43 and -53%) than with high reproductive performance ( 20 and -24%). When ES was 72 d, A and S intervals would reduce costs for high (-9 and -11%) but increase costs for low reproductive traits. Corresponding increases in CP/TDN required in diet would reduce gains in TDN/EBW only slightly. These results should aid in development of optimum selection criteria for stocks used for pure or rotation crossbreeding or as maternal parents of terminal crosses. PMID- 1752810 TI - Divergent selection for postweaning feed conversion in Angus beef cattle: I. Mean comparisons. AB - Each year from 1979 through 1983, 35 Angus bull calves were selected from a herd at the Eastern Ohio Resource Development Center to be individually fed in a 140-d postweaning performance test. From these 35 individually fed bulls, the three highest and three lowest for feed conversion (feed:gain) were selected and randomly mated to approximately 20 cows each. A different set of high vs low feed conversion sires was used each year. Four replicates (403 progeny) from high vs low sires were evaluated by sire groups for subsequent postweaning and carcass performance. Progeny were slaughtered when estimated by ultrasonic measurement to have 8.9 mm or more of subcutaneous fat at the conclusion of a 140-d postweaning performance test. Progeny with less than 8.9 mm of subcutaneous fat were fed for additional 28-d periods until they reached the required minimum. No differences were found between high and low feed conversion progeny for 140-d feed intake (P less than .30) although high feed conversion progeny gained .09 kg/d more weight (P less than .01) during the 140-d postweaning test. Differences tended to exist between high and low feed conversion progeny for unadjusted (P less than .15) and maintenance-adjusted (P less than .15) feed:gain ratios. Progeny of the high feed conversion group had greater subcutaneous fat (P less than .05) at the end of the 140-d postweaning test and when slaughtered (P less than .05), indicating a genetic difference for composition of BW gain between high- and low-sired progeny. However, no significant differences existed for any other carcass traits evaluated. Bulls had more desirable unadjusted (P less than .001) and maintenance adjusted (P less than .001) feed:gain ratios than heifers with increased 140-d ADG (P less than .001) and pen feed intakes (P less than .001). PMID- 1752811 TI - Divergent selection for postweaning feed conversion in Angus beef cattle: II. Genetic and phenotypic correlations and realized heritability estimate. AB - A single generation divergent selection study, replicated four times (1983, 1984, 1985, and 1986), was conducted to assess genetic differences between progeny of high and low feed conversion sires in Angus beef cattle and to determine correlated response for weight gain (ADG140), feed intake (AVFD140), and BW (OFFTSTWT) in a time- (140-d) and fat-constant (8.9 mm) period. Realized heritability estimates for unadjusted (feed/gain; FEFF140; .26) and adjusted feed conversion (adjusted as recommended by the BIF, 1986; ADJFDEFF; .46) were obtained. The difference in heritability estimates reflects variation accounted for by adjustment for BW differences, and thus maintenance requirements, of individual progeny. Phenotypic and "pseudo" realized genetic correlations of FEFF140 with ADG140, AVFD 140, and OFFTSTWT were -.33 and -.66, .49 and -.26, and .15 and -.41, respectively. Phenotypic and "pseudo" realized genetic correlations of ADJFDEFF with ADG140, AVFD140, OFFTSTWT, and FEFF140 were -.54 and -.59, .30 and -.23, .27 and -.36, and .97 and .49, respectively. Subcutaneous fat (as estimated by ultrasonic measurement; BF140) had phenotypic and "pseudo" realized genetic correlations with FEFF140 of -.33 and .66, respectively, and with ADJFDEFF of -.44 and -.58, respectively. PMID- 1752812 TI - Maternal breed of sire effects on postweaning performance of first-cross heifers and production characteristics of 2-year-old heifers. AB - Postweaning growth rates from weaning to 18 mo, fall condition score, pregnancy rates, and production to 2 yr of age were evaluated in a study of Angus (A)-, Pinzgauer (P)-, Red Poll (R)-, Simmental (S)-, and Tarentaise (T)-sired females from Hereford dams. First-cross heifers from the different sire breeds did not differ (P greater than .10) in initial weight. During a 140-d feed test, S gained 98.6 kg, exceeding (P less than .05) gains of P, 92.3; A, 91.4; and R, 87.3 kg but not T, 94.1 kg. Red Poll-sired heifers weighed less at the end of the 140-d test (P less than .05) than the other crosses, which did not significantly differ from each other. No breed of sire differences were found in gain from 140 d to fall weight. Simmental-sired heifers weighed more (P less than .05) than A- and R sired heifers at 18 mo. Breed of sire and year interacted to affect pregnancy rate of the yearling heifers when mated to Shorthorn sires for 45 d. Percentage of dystocia varied from a low of 26.3 and 28.9% for T- and A-sired heifers, respectively, to 54.4 and 60.8% for P- and S-sired heifers, respectively (P less than .05). Age of dam of heifers affected (P less than .05) weight at the different period end points but not gains after weaning. Age of dam also affected incidence of dystocia. Two-year-old heifers from young dams had more dystocia than heifers from older dams. Shorthorn-sired calves from 2-yr-old heifers with different sire breeds differed in birth weight (P less than .05) but not survival from birth to weaning, ADG from birth to weaning, weaning age, or weaning condition score. Average 200-d weight of calves from P-, S- and T-sired heifers exceeded those from A- and R-sired heifers by 10.7 kg, or 5.7%. PMID- 1752813 TI - Maternal breed of sire effects on postweaning performance of heifer and steer progeny: postweaning growth and carcass characteristics. AB - Heifer and steer progeny of 2-yr-old first-cross (F1) heifers and 3- to 6-yr-old F1 cows, from Hereford dams and five sire breeds, were evaluated for postweaning feedlot growth and carcass composition. Breeds of sire of dam were Angus (A), Red Poll (RP), Tarentaise (T), Simmental (Sm), and Pinzgauer (P). Calves from 2-yr old heifers were sired by Shorthorn, and calves from 3- to 6-yr-old dams were sired by Charolais. Breed of sire of dam was significant (P less than .05 to P less than .01) for total gain and final weight for female progeny from 2-yr-old dams. At all weights, Sm, P, and T ranked above A and RP. Progeny of A, P, Sm, and T F1 2-yr-old dams were not significantly different but were higher (P less than .05) than RP heifers in total feedlot gain. Breed of sire of dam was significant (P less than .05) for carcass weight and longissimus muscle area; T ranked highest and RP lowest. Breed was not significant for any growth traits of steer progeny of 2-yr-old dams. Breed was significant for marbling score; A ranked highest and exceeded (P less than .01) both RP and Sm steers. Breed was significant (P less than .05) for most growth traits in the heifer progeny of the 3- to 6-yr-old dams bred to Charolais sires. Heifer calves of the Sm group were heavier (P less than .05) than all other groups for most weights and total gain. For total gain, P and T were intermediate and A and RP lowest. For heifer carcass traits from 3- to 6-yr-old dams, breed was significant (P less than .05 to P less than .01) for carcass weight, longissimus muscle area, percentage of cutability, and estimated kidney, heart, and pelvic fat. Heifers from Sm-sired dams were heavier (P less than .05) than those from all other groups but ranked second to heifers from P for percentage of cutability. Marbling scores of RP heifer carcasses ranked highest of all groups. Breed was not significant (P greater than .05) for any of the weights or gains in steer progeny of 3- to 6-yr-old dams; however, the Sm and P groups ranked above A and RP for all feedlot test weights.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752814 TI - Efficacy of alternative multivariate best linear unbiased prediction models for genetic evaluation of swine. AB - A comparison of the accuracy of alternative BLUP evaluations of swine performance data is reported. A simulated data set of performance for days to market, backfat, number born alive, number weaned, and litter weight in six herds was used for the evaluation. The data structure was derived by using the performance records of six herds sampled from the American Yorkshire Club's STAGES (Swine Testing and Genetic Evaluation System) database. For growth traits, 10,360 pig records from 129 sires and 897 dams were recorded. For maternal traits, records on 2,598 litters of 1,209 sows from 147 sires and 585 dams were included. The actual observed performance of each record was removed and replaced with simulated performance. These simulated data were analyzed by within- and across herd BLUP models using STAGES and Animal Model (AM) procedures. Results indicate that the alternative BLUP procedures produced similar estimates. Correlations between STAGES and AM EPD ranged from .84 to .95. Correlations between STAGES EPD and true genetic value (G) ranged from .41 to .74, and correlations between AM EPD and G ranged from .40 to .74. On average, AM EPD had a .04 larger correlation with G than did STAGES EPD, although the difference in the correlations was not significant (P greater than .05). Trends in EPD for sires, dams, and pigs or sows were the same. Likewise, standard errors of prediction for AM EPD averaged 4% smaller than those for STAGES EPD. Computationally, the AM procedures used 15 to 20 times as much processing time as did STAGES procedures. PMID- 1752815 TI - Simulation of genetic and environmental interaction of three tropical hair sheep breeds. AB - The Texas A&M Sheep Simulation Model was used to examine genetic-environmental interactions (GEI) among Brazilian Somali, Morada Nova, and Santa Ines breeds and type and level of feed supplement in northeast Brazil. Two sets of simulations were conducted to examine effects of different supplement quality (napier grass vs cunha legume) and quantity (napier grass only). The analyses indicated the benefits from supplementing lambs at weaning during the dry season and from supplementing lactating ewes at the beginning of lambing season when forage is scarce. The cunha legume was an effective supplement, but choosing between cunha legume and napier grass is an economic consideration. Increasing the amount of napier grass supplement per ewe from 200 g/d to 400 g/d resulted in a significant GEI (i.e., different levels of response such as lamb mortality rate, lamb weaning weight, and lambing rate for different breeds). The Brazilian Somali was the least responsive, whereas the Santa Ines was the most responsive to supplementation. It was concluded that the level of supplement should be higher for the Santa Ines and Morada Nova than for the Somali. The amount of supplement should be regulated so that it neither substitutes for nor lowers the utilization of the native caatinga forage. None of the breeds was simulated to be superior in all environments. Thus, considering the wide range of resources of individual farmers, any one of these breeds may be the preferred choice, depending on the individual set of production resources. PMID- 1752816 TI - Body composition and fasting heat production from birth to 14 months of age for three biological types of beef heifers. AB - Thirty heifers were randomly sampled at five ages from each of the Hereford, Charolais, and Simmental herds at the U.S. Meat Animal Research Center to estimate association of fasting heat production (FHP) with body composition. Replicated measures of respiratory exchange were obtained for six heifers per breed at ages 2 d, 3 mo, 7 mo, 10 mo, and 14 mo using open-circuit calorimetry. Regression adjustment of FHP/live weight.75 to zero activity (AFHP) reduced the mean by 12% and variance among periods for the same animal by 42%. Daily AFHP (kcal/kg.75) was highest at 2 d (122), lowest at 10 mo (92) (P less than .01), and intermediate (103 to 106) at other ages and averaged 109, 106, and 102 for Charolais, Simmental and Hereford over all ages (P less than .05). Pooled within age correlations of AFHP were .77 with weight of carcass (CAR) nonfat or water and .75 with live and empty body weight (EBW) but were only .13 with fat weight. Prediction of AFHP within age groups was most accurate from multiple regression on the nonfat weight in visceral organs and blood (VOB), gastrointestinal tract (GIF), head, hide, and shanks (HHS), and CAR fractions (R2 = 61%, error SD = 21.5), from regression on nonfat in CAR alone (60%, 21.6), or from regression on chemical components in each of the four fractions (59%, 22.0), relative to EBW (55%, 22.9) or its four chemical components (58%, 22.3). Partial regressions were largest for water or nonfat (P less than .01) and were negligible for fat. Importance in predicting AFHP was two to eight times greater for nonfat in CAR than in other fractions because CAR was 60 to 65% of EBW. Lean mass is clearly a major predictor of nutrient requirement that is useful to evaluate effects of body composition on the efficiency of beef production. PMID- 1752817 TI - Response to environmental temperatures in Brahman calves during the first compared to the second day after birth. AB - Brahman calves (n = 28) were used to evaluate the effect of environmental temperature during the 1st or 2nd d after birth. Calves were removed from their dams within 30 min of birth (newborn; D0) before suckling or at 20 h of age and fasted for 4 h before treatment (day-old; D1). Calves were placed in either a warm (W; 25 degrees C) or a cold (C; 5 degrees C) environment for 2 h and either maintained in or transferred to, respectively, W for 22 h. Blood samples were collected via jugular catheters at 15-min intervals beginning at initial placement in W or C through 3 h and at 4, 5, 6, 8, 10, 12, 14, 18, and 24 h. Rectal temperature (Tr) was recorded with each sample. Following the 60-min and 12-h samples, each calf was administered 1 liter of colostrum from its dam. Serum or plasma was analyzed for glucose, lactate, plasma urea nitrogen, triglycerides, nonesterified fatty acids, insulin, cortisol, triiodothyronine (T3), and thyroxine (T4). Rectal temperature of D0C calves was lower (P less than .05) than that of other calves from 75 min through 3 h. Insulin, lactate, T3, and plasma urea nitrogen concentrations were not different among all calves. Higher (P less than .01) cortisol and T4 concentrations were observed in D0 than in D1 calves. Cortisol (P less than .008) and nonesterified fatty acid (P less than .05) levels were greater in C than in W calves. All D0 calves had lower (P less than .0001) glucose concentrations than D1 calves until the 12-h feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752818 TI - Effect of feeding regimen on behavior of growing-finishing pigs supplemented or not supplemented with folic acid. AB - The effect of restricted feeding on the frequency of abnormal behaviors and gastric ulcers was investigated in 72 market pigs. Half of the pigs were fed restricted (R) amounts of feed twice a day (0800 and 1600) and received 90 to 95% of the intake recorded for the other half, which were allowed ad libitum (A) access to feed with addition of feed once a day at 0800. In each feeding group, 24 pigs were supplemented with folic acid. The animals were housed in pairs and the behavior of each animal was recorded during 24 h at 18 and 20 wk of age. The results showed that the A group ate more frequently during light hours than the R group at 18 wk, but not at 20 wk. However, the frequency of eating behavior was higher in the R group than in the A group at 20 wk during the 2 h after feed distribution. Feeding regimen had an effect on the frequency of redirected behaviors during the 2 h preceding feed distribution. The percentage of time spent nibbling on the penmate was higher in R than in A pigs at 18 wk, whereas that of rooting on the penmate was higher at 20 wk. Moreover, the proportion of pigs performing redirected behaviors was higher in the R than in the A group at both ages. The overall frequency of gastric ulcers was similar in pigs given the two feeding treatments, but severe ulcers were more frequent in the R than in the A group. Some interactions were also found between feeding regimen and folic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752819 TI - Effects of synthetic hormone implants, singularly or in combinations, on performance, carcass traits, and longissimus muscle palatability of Holstein steers. AB - Seventy-two Holstein steers averaging 182 kg were assigned randomly to one of six treatment groups: 1) nonimplanted controls (C); 2) implanted with 36 mg of zeranol (Z); 3) implanted with 20 mg of estradiol benzoate and 200 mg of progesterone (EP); 4) implanted with 140 mg of trenbolone acetate (TBA); 5) implanted with 140 mg of trenbolone acetate plus 20 mg of estradiol benzoate and 200 mg of progesterone (TBA + EP); and 6) implanted with 140 mg of trenbolone acetate plus 36 mg of zeranol (TBA + Z). Each treatment group consisted of three replications of four animals per pen, which were implanted on d 0, 56, 112, and 168. Masculinity and muscling scores were assigned at 24 h preslaughter. Hide removal difficulty was scored by a plant supervisor. Quality and yield grade data were obtained at 24 h postmortem. Longissimus muscle (LM) steaks were removed and cooked for Warner-Bratzler shear (WBS) determinations and sensory panel (SP) evaluations. Over the entire feeding period (249 d), TBA + EP steers had higher (P less than .05) ADG than TBA + Z, TBA, and C steers. All treatments had higher (P less than .05) ADG than C, with the exception of TBA. The only feed efficiency differences were those following the 168-d implant time, when TBA steers were more (P less than .05) efficient than TBA + Z or C steers. The TBA + EP and TBA + Z steers were more (P less than .05) masculine and their hides were more (P less than .05) difficult to remove than those of EP and C steers. Carcass weights of TBA + EP steers were heavier (P less than .05) than those of TBA or C steers. The TBA + EP steers had larger (P less than .05) LM areas than Z, TBA, and C steers. Also, TBA + EP steers tended (P = .07) to have lower numerical yield grades than EP, Z, or C steers. Even though mean marbling scores and quality grades were similar (P greater than .05) among treatment groups, only 50% of TBA + EP carcasses graded low Choice or higher, compared with 100, 75, 82, 90, and 83% for C, TBA, Z, EP, and TBA + Z carcasses, respectively. The only meat palatability differences were that myofibrillar and overall tenderness scores tended to be lower (P = .07) for steaks from EP and TBA + Z than for steaks from Z and C groups. PMID- 1752820 TI - Degradation of myofibrillar proteins by extractable lysosomal enzymes and m calpain, and the effects of zinc chloride. AB - A study was conducted to examine the effects that physiological levels of m calpain (calpain requiring millimolar concentrations of Ca2+) extract and a lysosomal extract have on myofibrillar proteins in vitro, and the effects that zinc has on inhibiting proteolysis by these extracts. During a 22-h incubation period, the lysosomal extract degraded myosin heavy chain, alpha-actinin, desmin, troponin-I, and myosin light chains 1 and 2. The effectiveness of the lysosomal extract to degrade myofibrillar proteins was significantly affected by the presence or absence of EDTA. Zinc, which is a potent inhibitor of cysteine proteinases, prevented most, but not all, of the lysosomal extract-induced myofibrillar protein degradation. Incubation of myofibrils with m-calpain resulted in the hydrolysis of troponin-T, desmin, and a 58-kDa molecular weight protein, possibly vimentin, and 5 mM ZnCl2 completely blocked these changes. Results from this study indicate that the degradation by the lysosomal extract is far more extensive than the degradation that occurs with normal postmortem storage and that possibly a non-cysteine protease is present that is capable of hydrolyzing some myofibrillar proteins under this in vitro condition, because Zn2+ did not block all proteolysis. However, similar changes were induced by m calpain incubation and postmortem storage. PMID- 1752821 TI - Factors influencing intermuscular fat and other measures of beef chuck composition. AB - Carcasses from 59 steers produced from the mating of Braford, Simbrah, Senepol, and Simmental bulls to Brahman- and Romana Red-sired cows and Brahman bulls mated to Angus cows were used in this study. Effects of sire breed and feeding calves vs yearlings on fat depots in the chuck, when steers were fed to 1.0 cm external fat, were determined. Breed of sire and feeding calves vs yearlings had no effect (P greater than .05) on percentage of intermuscular fat. However, carcasses from Braford-sired steers had a higher (P less than .05) percentage of dissectable subcutaneous fat on the chuck than did those from other breed groups. Carcasses from Simmental-sired steers were superior (P less than .05) to those from Braford sired steers in USDA yield grade and had a higher average marbling score (P less than .05) than the Simbrah-sired group. Estimated kidney, pelvic, and heart (KPH) fat was higher (P less than .05) in carcasses from Brahman-, Simbrah-, and Senepol-sired steers than in Braford-sired steers. Steers fed as calves had higher percentages (P less than .05) of KPH fat and major chuck muscles than did those fed as yearlings. The best single predictor of percentage of intermuscular fat within the chuck was adjusted fat over the ribeye (R2 = .46). PMID- 1752822 TI - Using calcium chloride injection to improve tenderness of beef from mature cows. AB - The objective of this investigation was to determine the effect of calcium chloride (CaCl2) injection on Warner-Bratzler shear force (WBS), sensory panel ratings, and collagen traits of mature cow beef. Within 30 min of exsanguination, subprimals (top round, TR; top sirloin, TS; strip loin, SL) from alternate sides of the carcass were injected with a .3 M CaCl2 solution (10% of the subprimal weight) and aged for 1, 7, or 14 d. The corresponding cold-boned cuts of the other side served as a control. Injecting CaCl2 eliminated the requirement for extended postmortem storage, as indicated by d 1 WBS. During the 14-d aging period, WBS of noninjected cuts decreased by 2.59 kg, whereas WBS of CaCl2 injected samples decreased by only .35 kg. Compared with control cuts, CaCl2 injection improved (P less than .05) d-14 WBS of steaks from SL, TS, and TR by 41.1, 40.1, and 15.3%, respectively. Additionally, CaCl2-injected subprimals exhibited higher (P less than .05) sensory panel tenderness ratings, lower (P less than .05) amounts of detectable connective tissue, and shorter (P less than .05) sarcomere lengths. No differences (P greater than .05) were observed in any quantitative collagen traits between CaCl2-injected and control cuts. These results indicate that CaCl2 injection improved ultimate tenderness and sensory ratings of meat from mature cow cuts. PMID- 1752823 TI - Effects of heating time and sodium metabisulfite on the nutritional value of full fat soybeans for chicks. AB - Two 21-d trials were conducted to evaluate the effect of heating time and sodium metabisulfite (SMBS) on the nutritional value of full-fat soybeans for chicks. In Trial 1, four pen-replicates of eight chicks each were fed corn-based diets (19% CP; 3,167 kcal of ME/kg) containing either 44% CP soybean meal or full-fat soybeans. The soybeans either were unheated or were autoclaved at 121 degrees C for 10, 20, 30, 40, 60, or 90 min. Soybean oil was added to the soybean meal diet to make it isoenergetic with the soybean diets. Trypsin inhibitor, urease activity, and the solubility of protein in the soybeans decreased as heating time increased. Weight gain increased and feed:gain and pancreas weights decreased quadratically (P less than .01) with heating time. Rate and efficiency of gain were maximized when the soybeans were heated for 40 min; further heating for 60 or 90 min reduced performance. In Trial 2, SMBS was added at levels of 0, 1, or 2% to full-fat, unheated soybeans or to soybeans before autoclaving at 121 degrees C for 10, 20, or 40 min. Four pen-replicates of seven chicks each were fed corn-soybean diets (19% CP; 3,144 kcal of ME/kg) with 12 treatments in a factorial arrangement of heating times and SMBS levels. The rate and efficiency of chick weight gain improved linearly (P less than .01) and pancreas weights decreased linearly (P less than .01) as heating time increased. Less heating time was required to maximize performance and minimize pancreas weights when SMBS was added, resulting in a heating time x SMBS interaction (P less than .05). Under the conditions of this research, chicks fed full-fat soybeans achieved maximum performance when the soybeans were heated at 121 degrees C for 40 min, and SMBS decreased by one-half the heating time required to inactivate the trypsin inhibitors. Trypsin inhibitor activity in soybeans was more closely related to their nutritional value than was urease activity. PMID- 1752824 TI - Effects of dietary pH and phosphorus source on performance, gastrointestinal tract digesta, and bone measurements of weanling pigs. AB - Crossbred pigs (n = 144, average age and weight = 28 +/- 3 d, 7.5 kg) were used in two 6-wk trials to assess the effects of dietary pH and P source on growth performance, gastrointestinal digesta pH and chloride ion concentration (Cl-), and bone characteristics. Treatments were randomly allotted within blocks (based on weight within gender) to a 3 x 2 factorial arrangement with three dietary pH levels (5.4, 6.0, and 6.7) and two P sources: dicalcium phosphate (DCP) and defluorinated phosphate (DFP). Pigs fed the pH 6.7 diet had reduced ADG (P less than .01) and average daily feed intakes (ADFI; P less than .001) during wk 1 to 3 and overall compared with pigs fed the pH 6.0 diet, but ADG and ADFI were not affected when the pH 5.4 diet was fed. There was a dietary pH x P source interaction (P less than .05) for ADFI. Pigs had decreased ADFI as dietary pH was increased from 6.0 to 6.7 for both DCP and DFP, but ADFI was similar for the pH 6.0 and 5.4 diets with DFP, whereas ADFI was greater for the pH 5.4 diet with DCP. Dietary pH did not influence ADFI:ADG ratio (F:G; P greater than .05), and P source had no effect (P greater than .05) on either ADG, ADFI, or F:G.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752825 TI - Toxicity and tissue accumulation of copper in chicks fed casein and soy-based diets. AB - Experiments were conducted to study Cu toxicity in chicks fed casein or soy containing diets containing graded levels of excess CuSO4.5H2O. Differences between diets in measures of Cu toxicity were pronounced. Addition of 800 mg of Cu/kg to a casein-dextrose semipurified diet decreased weight gains by 63%, but the same addition of Cu to a corn-soybean meal complex diet decreased gains by only 8%. At all levels of Cu supplementation (100, 200, 400 or 800 mg/kg), Cu deposition in the liver was increased markedly in chicks fed casein diets compared with those fed the complex diet. Substituting soy-protein concentrate for casein in the semipurified diet resulted in a marked decrease in Cu toxicity as measured by weight gain reductions and tissue accumulation of Cu. PMID- 1752826 TI - Plasma levels of oxytetracycline, doxycycline, and minocycline in pigs after oral administration in feed. AB - Steady-state plasma levels were determined for oxytetracycline (OTC), doxycycline (DC), and minocycline (MC) after medication with different in-feed concentrations. Each concentration of the three tetracyclines was examined in six pigs. The animals were housed in individual pens and fed twice daily with an interval of 12 h. All pigs consumed their feed within 1 h after it was provided. Concentrations of 400, 800, 1,600, and 2,400 mg of OTC per kilogram of feed induced steady-state plasma levels ranging from .13 to .22, .19 to .50, .39 to 1.43, and 1.41 to 2.14 micrograms/ml, respectively. On a feed intake basis, pigs received 13, 26, 54 to 81, and 108 mg of OTC per kilogram of BW per day, respectively. Steady-state plasma levels after medication with 200, 400, and 800 mg of DC or MC per kilogram of feed ranged from .37 to .89, .71 to 1.14, and 1.62 to 3.18 micrograms/ml for DC and from .21 to .60, .43 to 1.05, and 1.19 to 2.62 micrograms/ml for MC. Pigs consumed 7, 13, and 26 mg of DC and 9, 18, and 36 mg of MC per kilogram of BW per day, respectively. For all three tetracyclines there was an increase in steady-state plasma levels when concentrations in feed or per kilogram of BW increased. Plasma levels were determined with both a HPLC method and a microbiological method. A good correlation existed between the results obtained by both methods. It was concluded that based on plasma levels and known in vitro activity DC and MC could be good alternatives for OTC to treat respiratory tract infections in pigs. PMID- 1752827 TI - Recombinant porcine somatotropin: an immunotoxicology study. AB - The present study was designed to determine the effect of recombinant porcine somatotropin (rpST; 5, 15, or 25 mg.pig-1.d-1 for 57 d) on a variety of immune function variables. We observed no significant effect of rpST treatment on the gross pathology of the pigs, histopathology of the immune system organs, total and differential white blood cell counts, lymphocyte blastogenic response to mitogens, or the neutrophil functions of chemotaxis, ingestion, reduction of cytochrome C, iodination, and antibody-dependent cell-mediated cytotoxicity. Those variables that were significantly affected by rpST treatment include a decreased hemoglobin and packed red blood cell volume (at some time points for all three rpST dosages), a decrease in plasma protein level at the 25-mg dose, a small increase in neutrophil random migration (at all three rpST dosages), and a decrease in IgG antibody response to tetanus toxoid at 15 d after immunization (but not at d 8, 22, or 29). Additionally, rpST treatment was associated with a decreased rate of BW gain (at 15-mg dose), increased liver and kidney weights (at all three dosage levels), and an increased incidence of renal tubular cytoplasmic vacuolation of minor severity. There were no observed differences in the overall health of the pigs due to rpST treatment, based on clinical observations as well as determination of antibody titer to, and isolation of, common swine pathogens. Therefore, there was no evidence that the observed influence of rpST treatment on immune function would be clinically relevant. PMID- 1752828 TI - The pharmacokinetics and residues of clenbuterol in veal calves. AB - Seven female Brown Swiss calves were used to study the pharmacokinetics of clenbuterol after an effective anabolic dosage of 5 micrograms/kg of BW was given twice daily for 3 wk. Analyses of clenbuterol concentrations in different tissues was done by enzyme immunoassay (EIA). Tissue samples were taken from three calves on the last day of administration and from two more after 3.5 or 14 d of clenbuterol withdrawal. The rate of clenbuterol elimination was dependent on time and tissue. Clenbuterol concentrations in the lung dropped from a mean of 76 ng/g to a level of less than .08 ng/g after 14 d, whereas in the liver the clenbuterol concentrations decreased from 46 ng/g to .6 ng/g within 14 d of withdrawal. Highest levels were always found in the eye: 118 ng/g, 57.5 ng/g, and 15.1 ng/g after 0, 3.5, and 14 d of withdrawal, respectively. These data reveal that different compartments contribute to the elimination of clenbuterol; therefore, concentrations in urine do not follow first order kinetics. An initial rapid decline in the concentration of clenbuterol in urine with a half-life of 10 h is followed by a slower elimination with a half-life of about 2.5 d. Treatments using the anabolic dose of 5 micrograms/kg of BW require longer withdrawal times than the therapeutic dose (.8 micrograms/kg BW). PMID- 1752829 TI - Exogenous opioids increase plasma prolactin in Holstein calves primarily via a dopaminergic mechanism. AB - A study was conducted to determine whether exogenous opioids increase prolactin (PRL) secretion in Holstein heifer calves via a dopaminergic mechanism. Twenty four Holstein heifer calves ranging in age from 5 to 7 mo were assigned to one of four treatment groups (six/treatment): 1) injection of saline (SAL); 2) injection of a synthetic enkephalin (D-Ala2, N-Me-Phe4, Met(O)5-ol enkephalin; DAMME); 3) injection of DAMME after pretreatment with the long-acting dopamine agonist 2 bromo-alpha-ergocryptine; or 4) injection of thyrotropin-releasing hormone (TRH) after pretreatment with 2-bromo-alpha-ergocryptine. Calves were equipped with indwelling jugular cannulas on d 1, and baseline plasma PRL concentrations were established. Animals receiving 2-bromo-alpha-ergocryptine were injected s.c. 3 h after the last baseline sample was drawn on d 1. On d 2, calves assigned to receive SAL, DAMME, or TRH were injected 2 h after the start of sampling, and sampling was continued for an additional 4.5 h. Basal plasma PRL was lower (P less than .01) on d 2 in calves injected with 2-bromo-alpha-ergocryptine than baseline levels on d 1. Plasma PRL was higher (P less than .01) in calves not pretreated with 2-bromo-alpha-ergocryptine after DAMME injection on d 2 but was not different after DAMME injection in calves pretreated with 2-bromo-alpha ergocryptine. In contrast, plasma PRL increased (P less than .01) after TRH injection on d 2 in calves pretreated with 2-bromo-alpha-ergocryptine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752830 TI - Suppression of sheep and goat lymphocyte proliferation by sheep, goat, and sheep x goat hybrid trophoblast tissue cultures. AB - Immunosuppressive activity of conditioned medium from cultured ovine, caprine, and hybrid trophoblast tissue was examined. Conceptuses were obtained from naturally mated donor ewes and does at d 20 of gestation and trophoblast tissue was cultured for 24 h in medium supplemented with 15% calf serum and 1% antibiotic/antimycotic. Conditioned medium was added to pokeweed mitogen stimulated sheep and goat lymphocyte cultures. Quantification of [3H]thymidine uptake by cells was used to measure lymphocyte proliferation. Ovine, caprine, and hybrid conditioned medium effectively suppressed sheep and goat lymphocyte proliferation (P less than .01). There were no differences (P greater than .05) between the immunosuppressive activity of the three tissue types on either sheep or goat lymphocytes. For all treatment groups, sheep lymphocytes were suppressed more than goat lymphocytes (P less than .05). These results indicate that, at d 20 of gestation, sheep x goat hybrid trophoblast tissue is capable of suppressing pokeweed mitogen-stimulated lymphocyte proliferation. PMID- 1752831 TI - Comparison of urea treatment with established methods of sorghum grain preservation and processing on site and extent of starch digestion by cattle. AB - To determine the effect of dry (D); reconstituted and ensiled (R); reconstituted and acid-treated (A); and urea-treated, high-moisture (U) sorghum grain on starch digestibility, four Angus x Hereford steers (means BW = 350 kg) with duodenal and ileal cannulas were used in a 4 x 4 Latin square design. Diets consisting of 69% ground sorghum grain were fed every 2 h in equal portions (8.2 kg/d). Diets averaged 46.5% starch and 12% CP, except for U, which averaged 14% CP due to urea treatment. Ytterbium attached to sorghum was used as a particulate marker. Duodenal, ileal, and fecal samples were taken 1 h postfeeding after a 14-d adaption to diets. Whole samples were analyzed. Preduodenal starch digestion (%) was 89, 83, 76, and 70, and starch digestion over the total tract was 99, 97, 95 and 91 for R, U, A, and D, respectively. Starch digestion proximal to each site (duodenum and ileum) was enhanced (P less than .05) by R and U compared with D. Within the small intestine, there was a linear relationship (P less than .003) between starch digestion and daily starch supply. However, digestibility of starch in the small intestine (mean = 45%) was not different among diets. Apparent digestibility of starch in the large intestine was not significantly different from digestibility in the small intestine. Urea-treated sorghum grain was equivalent to reconstituted, ensiled sorghum in digestion characteristics and was superior to dry sorghum. PMID- 1752832 TI - Effects of cold environment and intake level on the energetic efficiency of feedlot steers. AB - The effects of cold climatic conditions on energy partitioning were investigated with 49 Hereford-type steers fed an all-concentrate, barley-based diet in a 2 x 3 factorial comparative slaughter trial. Steers (seven per treatment) were kept either indoors or outdoors (n = 2) and fed at 50, 65, or 80 g of DM/kg of BW.75 (n = 3) for up to 106 d. Mean temperatures were 16.9 +/- 2.7 degrees C and -7.6 +/- 6.8 degrees C in indoor and outdoor locations, respectively. Steers housed indoors grew 49% faster (P less than .001) and had 51% better gain: feed ratios (P less than .05) than those kept outdoors. Outdoor steers retained 65% less (P less than .001) energy. Estimated fasting heat production in the outdoor steers was 18% higher (P less than .01) and efficiency of ME use for maintenance 14% lower (P less than .01) than in the indoor steers, which resulted in an estimated increase of 41% in the ME requirements for maintenance in the outdoor steers. The NEg content of the diet was decreased from 1.29 Mcal/kg in the indoor steers to .76 Mcal/kg in the outdoor steers. Outdoor steers deposited 21% of their energy as protein, whereas indoor steers deposited only 14% of their energy as protein, which could explain the low NEg value of the diet in the cold environment. It was concluded that the main factors contributing to reduced energetic efficiency in the cold were an increased maintenance requirement and a greater proportion of the dietary energy retained as protein. PMID- 1752833 TI - Technical note: effectiveness of different methods of continuous marker administration for estimating fecal output. AB - Six ruminally fistulated crossbred steers (BW = 369 kg) were used in a randomized complete block experiment to test the efficacy of continuous-infusion pumps and controlled-release boluses for administering external markers to predict fecal output. Steers, limit-fed chopped alfalfa hay at 2% of BW daily, were fitted with continuous-infusion pumps that administered Co-EDTA and YbCl3 solutions intraruminally. In addition, a controlled-release bolus containing Cr2O3 was inserted into the rumen of each steer. Fecal grab samples were taken every 6 h for 7 d during initial marker equilibration; after this period, fecal grab samples were taken every 3 h for 48 h to evaluate diurnal variation patterns. Steers were subsequently fitted with fecal bags for 7 d to allow total fecal collection. Grab samples also were taken during the total fecal collection period at 0600 (AM) and 1400 (PM). The marker X time effect was nonsignificant. Similarly, time of grab sampling (AM or PM) did not affect estimates of fecal output (P greater than .10), but the Cr2O3 bolus overestimated fecal output (P less than .05). Fecal marker concentrations during the 48-h profile showed little diurnal variation regardless of marker used. All markers equilibrated in the feces at approximately 100 to 120 h after initiating infusions. The continuous infusion pumps evaluated were efficacious for administering markers for estimating total fecal output in limit-fed steers; however, the Cr2O3 boluses evaluated overestimated fecal output when the manufacturer's suggested release rate was used for fecal output calculations. PMID- 1752834 TI - Effect of a Saccharomyces cerevisiae culture on lactate utilization by the ruminal bacterium Selenomonas ruminantium. AB - The objective of this study was to examine the effects of a Saccharomyces cerevisiae culture (YEA-SACC) on lactate utilization by the predominant ruminal bacterium Selenomonas ruminantium. Lactate uptake was stimulated by YEA-SACC concentrations between 2.5 and 10 g/liter, and the 5-g/liter level increased uptake 3.8-fold. When YEA-SACC concentrations were increased above the 5-g/liter level lactate uptake was decreased, but 10 g/liter still stimulated uptake more than threefold. A filter-sterilized YEA-SACC filtrate also increased lactate uptake more than fourfold at all concentrations tested (10 to 100 microliters/ml), and the 25-microliters/ml level increased uptake ninefold. Growth of S. ruminantium in medium that contained 2 g/liter of DL-lactate was stimulated more than twofold by either 2 or 5% (vol/vol) YEA-SACC filtrate after 24 h. The YEA-SACC filtrate also increased the production of acetate, propionate, total VFA, and YLACTATE (grams of cells/mole of lactate) from lactate-grown cells. Because the increase in propionate production was greater relative to acetate, a decrease in the acetate:propionate ratio was observed. Growth on lactate and uptake of radiolabeled lactate by S. ruminantium was stimulated by a filter-sterilized YEA-SACC filtrate. The concentration of L-malic acid in the YEA SACC filtrate was 4.9 mM, and it seemed that L-malic acid played a role in the stimulation of growth on lactate as well as lactate uptake by S. ruminantium treated with YEA-SACC. PMID- 1752835 TI - Technological to a fault or faulty approach to technology development? PMID- 1752836 TI - From technical jargon to plain English for application. AB - These examples of translating technical jargon into plain English application words, acronyms, letter codes, and simple tests were necessary as we developed Precision Teaching. I hope our experience is useful to others facing the problems of applying technology in practical settings. At the least, our experience should give you an idea of the work and time involved in making your own translations. Above all, be patient. Accurate plain English translations do not come easily. They cannot be made at your desk. A search often takes years to produce one new accurate plain English translation. Rapid publication pressures, journal editorial policies, and investments in materials, books, and computer programs all combine to hamper these translations. It's possible that you will find some of our plain English equivalents useful in your own applied behavior analysis applications. PMID- 1752837 TI - Increasing habilitative services for persons with profound handicaps: an application of structural analysis to staff management. AB - We evaluated a structural analysis methodology for enhancing the utility of a staff management program. In Experiment 1, a structural analysis of direct-care staff behavior in a mental retardation facility revealed differences in work patterns over time. Specific times were identified when few basic care duties were necessary and staff engaged in nonwork activity. In Experiment 2, a management program was implemented to increase staff members' training activities during periods identified through the structural analysis. The program was accompanied by increases in training activities and decreases in nonwork behavior. The improvements were maintained during a 43-week period while the most labor-intensive component of the program was withdrawn. Staff acceptability measures indicated a positive response to the management intervention, although responses varied across components within the multifaceted program. The increased training was accompanied by beneficial changes among clients with profound handicaps. Results are discussed regarding practical considerations for improving staff performance and for adopting innovations resulting from applied research. PMID- 1752838 TI - Reactivity in self-recording: obtrusiveness of recording procedure and peer comments. AB - Reactivity refers to behavior change that occurs during self-recording without specific programming of consequences. We analyzed the effects of obtrusiveness of recording procedure and peer comments on reactivity to self-recording. Three first-grade students in Experiment 1 completed math questions during a 5-min work period. When we gave the children recording devices and told them to try to complete more questions than the highest number they had previously completed, math performance increased, as did the number of verbalizations about it. Two children showed more reactivity when they used the more obtrusive recording device. Because the increase in math performance corresponded closely to increases in peer comments, we manipulated peer comments directly in Experiment 2. Four second-grade students completed a math task and an alphabet task. Three of the students showed increased math performance during periods when peer comments occurred compared to periods when peer comments did not occur. Although the data from the math task suggested that peer comments can enhance reactivity, we did not observe this relationship with the alphabet task. These results suggest that the conditions necessary to produce desirable results through self recording are complex and contextually specific. PMID- 1752839 TI - Effects of self-management training and reinforcement on the transfer of improved conduct in the absence of supervision. AB - The instruction, maintenance, and transfer of training of social skills of 3 seriously emotionally disturbed adolescents were accomplished by a self management training and reinforcement package. During baseline sessions these students, who were covertly filmed in their classroom, averaged over 90% off-task or socially inappropriate behavior while their teacher was out of the room. They showed similar behaviors when walking between classes, unattended by their teacher. Treatment was introduced in the classroom and consisted of social skills and self-management training and reinforcement. Treatment procedures included instruction, modeling, and role playing of social skills, as well as self assessment, self-recording, and self-reinforcement for correct approximations of these skills. After 5 weeks of training, all subjects demonstrated substantial improvements in the classroom during the teacher's absence and when distracted by other students; however, transfer of social skills did not occur to the between class setting until students were given explicit instruction to initiate self managing procedures in this setting. PMID- 1752840 TI - A brief functional analysis of aggressive and alternative behavior in an outclinic setting. AB - We conducted a brief functional analysis to identify maintaining variable for aggressive behavior and an alternative replacement response during a 90-min outpatient evaluation of 3 individuals with severe handicaps. During the initial analogue assessment, which focused on identifying maintaining contingencies for aggressive behavior, each participant displayed a substantially greater frequency of aggressive behavior during one condition than during any other. The contingency that produced the highest percentage of aggressive behavior was then presented for the occurrence of a specific alternative behavior (a mand). During this contingency reversal phase, each participant displayed a substantial reduction in aggressive behavior and a substantial increase in alternative behavior, thus providing a direct analysis of the equivalency of the contingency for maintaining either behavior. PMID- 1752841 TI - The effects of severe behavior problems in children on the teaching behavior of adults. AB - Applied behavior analysts have focused on how adults can influence the problem behavior of children using a variety of behavior modification strategies. A related question, virtually unexplored, is how the behavior problems of children influence adults. This child-effects concept was explored empirically in a study involving 12 adults who were asked to teach four pairs of children in which one member of the pair exhibited problem behavior and the other typically did not. Results demonstrated that problem children displayed tantrums, aggression, and self-injury contingent on adult instructional attempts but not at other times, whereas nonproblem children showed little or no problem behavior at any time. Importantly, from a child-effects perspective, adults engaged in teaching activities with nonproblem children more often than with problem children. Also, when an adult worked with a problem child, the breadth of instruction was more limited and typically involved those tasks associated with lower rates of behavior problems. The implications of these results are discussed with respect to theories of escape behavior, current assessment practices, and intervention issues related to maintenance. The existence of child effects suggests that problem behavior may be better understood when it is conceptualized as involving a process of reciprocal influence between adult and child. PMID- 1752842 TI - Linking descriptive and experimental analyses in the treatment of bizarre speech. AB - Descriptive and experimental methods were used to analyze the environmental determinants of an adult's bizarre speech. A descriptive analysis of behavior under natural conditions indicated that bizarre vocalizations occurred most often in the presence of task-related demands and in the absence of adult attention. Further, bizarre speech occurring during tasks was followed frequently by the cessation of task demands by staff or the subject's voluntary disengagement from task-related activities; bizarre speech observed during noninteractional periods (i.e., in the absence of adult attention) was frequently followed by staff attention. The escape and attention hypotheses were tested under analogue conditions. Results of the experimental analysis supported only the attention hypothesis; that is, bizarre speech appeared to function as an attention producing behavior. The functional analysis data were used to select two different yet functionally equivalent treatments. The first treatment provided the subject with noncontingent scheduled attention. The second intervention taught the subject social language skills in the form of initiation and expansion statements. Both interventions were effective in suppressing maladapted speech. Advantages of linking descriptive and experimental analyses are discussed. PMID- 1752843 TI - Teaching self-administration of suctioning to children with tracheostomies. AB - We examined the effectiveness of using dolls to teach young children with tracheostomies to self-administer a suctioning procedure. Four children between the ages of 5 and 8 years, who had had tracheostomies for 6 months or longer, participated. After skills were taught via doll-centered simulations, in vivo skills were evaluated. All of the training and probe sessions were conducted in the participants' classrooms or homes. Results of a multiple baseline design across subjects and skill components indicated that the performance of all children improved as a function of training. Skill maintenance was demonstrated by all participants during follow-up assessments conducted 2 to 6 weeks posttraining. Results of a questionnaire completed by caregivers and interviews with the children revealed high levels of satisfaction with the training procedures and outcomes. PMID- 1752844 TI - Teaching adults with severe and profound retardation to exit their homes upon hearing the fire alarm. AB - Prompting, modeling, and differential reinforcement with client-chosen rewards were used to teach 3 nonverbal people with severe to profound mental retardation to exit their group homes at the sound of the house fire alarm, using a multiple baseline design. All 3 participants learned to exit independently in less than 2 min in all experimenter-initiated surprise fire drills and in the majority of staff-initiated surprise fire drills. Each participant was also able to exit from five areas of the house from which teaching was not done. PMID- 1752845 TI - Assessing stimulus control in natural settings: an analysis of stimuli that acquire control during training. AB - When a learner is taught a new response, the stimuli that influence its display are often unknown. The presence or absence of these stimuli alters the probability of occurrence of the response. By identifying the stimuli influencing the probability of newly acquired responses, interventionists may program for their generalization more effectively and efficiently. This investigation describes the application of an operant methodology to assess functional relationships between responses and specific stimulus variables. Four young adults with moderate mental retardation were taught to include "please" as part of requests they made in school. Four environmental stimuli, present during training, were assessed for the controlling properties they acquired. Each of the four was assessed prior to and after training by presenting it in isolation (i.e., the other three were varied). If the presence of a single stimulus associated with training did not occasion "please," then pairs of stimuli were probed. The results revealed that single-stimulus probing occasioned responding by only 1 learner; paired-stimulus probing set the occasion for including "please" by 2 others. Control of the 4th learner's responding was lost before training was introduced, because he began including "please" in his requests during baseline. The implications of these results are discussed in terms of analyzing stimulus control and promoting stimulus generalization. PMID- 1752846 TI - Using time delay to promote spontaneous speech in an autistic child. AB - One of the frequently observed deficits in autistic children is their lack of spontaneous speech. We used a multiple baseline across behaviors to investigate the effectiveness of a time delay procedure for inducing spontaneous speech in a 10-year-old male autistic child during play. We first taught the child to imitate the experimenter's verbal prompts that described the child's motor response. Once the child reached criteria on imitation, we implemented baseline wherein an immediate verbal prompt for speech was provided after each of the child's motor responses. Intervention consisted of a gradual delay in the presentation of the verbal prompts. The time delay effectively increased the child's spontaneous speech on trained items; some generalization to untrained items also occurred, but only within the same behavioral class of car play. Generalization was also observed across settings. Spontaneous speech remained at high levels during the 4 month maintenance for the behavior of car play but decreased for a second behavior. Decreases in the child's response latencies suggest that spontaneous speech may be an anticipatory verbal response. PMID- 1752847 TI - Effects of caloric level on ruminating. AB - A series of recent studies has shown that a number of dietary variables affect ruminative behavior in institutionalized retarded persons. This experiment extends an earlier study that examined the influence of the caloric level of the diet on the frequency of ruminating. Subjects consumed regular portions of food that varied between phases from normal to high caloric levels. The data show a clear but modest inverse relation between the caloric value of the diet and the rates of postmeal ruminating. PMID- 1752848 TI - Reexposure to fluoxetine after serious suicide attempts by three patients: the role of akathisia. AB - Considerable controversy exists regarding the relationship between fluoxetine and the emergence of suicidal ideation. Three cases are presented of patients who were reexposed to fluoxetine after having previously made a serious suicide attempt during fluoxetine treatment. All three patients developed severe akathisia during retreatment with fluoxetine and stated that the development of the akathisia made them feel suicidal and that it had precipitated their prior suicide attempts. The akathisia and suicidal thinking abated upon the discontinuation of the fluoxetine or the addition of propranolol. The emergence of suicidal ideation during treatment with fluoxetine may be secondary to the development of akathisia. Gradual increments of fluoxetine dose and the prompt recognition and treatment of akathisia may reduce further the rare occurrence of suicidal ideation during fluoxetine treatment. PMID- 1752849 TI - Clozapine and jaw dyskinesia: a case report. AB - No convincing case of tardive dyskinesia has been associated with clozapine. We briefly discuss a case of clozapine-induced reversible initial dyskinesia described in the German literature, and we report a case of jaw dyskinesia in a 49-year-old female schizophrenic. The dyskinesia appeared 2 weeks after the patient started clozapine treatment, did not respond to anticholinergic medication, and has continued for more than 1 year while the patient has remained on clozapine treatment. The patient had taken haloperidol (less than or equal to 5 mg/day) for 5 weeks before starting clozapine treatment. These are the only two cases of dyskinesia associated with clozapine use that are known to us. They raise the possibility that clozapine can induce dyskinesia. PMID- 1752850 TI - Thrombocytopenia associated with carbamazepine: a case series. AB - Carbamazepine is increasingly being used in the acute and maintenance treatment of patients with bipolar disorder. Thrombocytopenia represents a serious adverse effect of carbamazepine with which clinicians need to be familiar. The authors describe the course of thrombocytopenia associated with carbamazepine in four patients with bipolar disorder. In all cases, thrombocytopenia appeared 14 to 16 days after the initiation of carbamazepine; also in all cases the platelet count completely recovered within 7 days after the carbamazepine treatment was discontinued. Thrombocytopenia secondary to carbamazepine appears soon after the initiation of treatment and is rapidly followed by recovery after drug discontinuation. PMID- 1752851 TI - P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study. AB - BACKGROUND: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. METHOD: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. RESULTS: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. CONCLUSION: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity. PMID- 1752852 TI - An open label trial of alprazolam in comorbid irritable bowel syndrome and generalized anxiety disorder. AB - BACKGROUND: The irritable bowel syndrome (IBS) is very prevalent and psychiatric comorbidity runs high. A significant proportion of generalized anxiety disorder (GAD) patients manifest concurrent IBS. METHOD: We conducted a 14-week, open label trial of the triazolobenzodiazepine alprazolam in 32 patients with comorbid generalized anxiety and IBS. At the end of a 2-week placebo run-in, eligible subjects received 6 weeks of active drug therapy. RESULTS: Ninety-four percent of subjects (N = 25) had a full or partial anxiolytic response at the 6th treatment week (p less than .001). Eighty-nine percent (N = 24) experienced a concomitant reduction in IBS severity. For the majority, these dual benefits were still evident at the conclusion of a 4-week drug taper (p = .05) and achieved a trend (p = .07) at a 4-week postdrug discontinuation visit. CONCLUSION: Alprazolam was safe, effective, and well tolerated during the acute treatment of comorbid GAD and IBS; only a limited posttreatment rebound was observed. PMID- 1752853 TI - Cocaine-induced psychosis. AB - BACKGROUND: Chronic stimulant use can produce a paranoid psychosis that is similar to acute paranoid schizophrenia. While this phenomenon has been systematically explored in amphetamine abusers, it has been relatively unexplored in a systematic fashion in cocaine abusers. METHOD: The experience of cocaine induced psychosis was evaluated in 55 individuals consecutively admitted for treatment of DSM-III-R cocaine dependence. Each subject was interviewed about their experiences of psychosis while intoxicated by means of a standardized, semistructured interview. RESULTS: Fifty-three percent (29/55) of those interviewed reported experiencing transient cocaine-induced psychosis. There was no significant difference in lifetime amount of cocaine use or amount of cocaine use in the month before admission between those who experienced psychosis and those who did not. The psychosis-positive group used significantly more cocaine in the year prior to admission (p less than or equal to .02) and had a longer duration of use (p less than or equal to .01). Males were significantly (p less than or equal to .05) more likely than females to develop psychosis. Ninety percent (26/29) developed paranoid delusions directly related to drug use. Ninety six percent (28/29) of the subjects experienced hallucinations: 83% (24/29), auditory hallucinations; 38% (11/29), visual hallucinations; and 21% (6/29), tactile hallucinations. Twenty-seven percent (15/55) of subjects developed transient behavioral stereotypies. CONCLUSION: Cocaine-induced paranoia is a common experience among chronic users. Amount and duration of use are related to its development. Implications for a kindling model of cocaine-induced psychosis will be discussed. PMID- 1752854 TI - Susceptibility to spontaneous MAOI hypertensive episodes. PMID- 1752855 TI - Pimozide in clinical psychiatry. PMID- 1752856 TI - Serotonin and behavior: emphasis on motor control. AB - Electrophysiologic studies of brain serotonergic neurons in behaving animals indicate that their activity is closely related to the sleep-wake-arousal cycle and to certain specific types of repetitive motor activity. A variety of other environmental and physiologic manipulations are ineffective in altering the activity of this neurochemical system. An attempt is made to relate these results to well-known involvement of brain serotonin in human affective disorders. PMID- 1752857 TI - Hypothalamic serotonin in treatments for feeding disorders and depression as studied by brain microdialysis. AB - Microdialysis was used to measure changes in extracellular serotonin in the hypothalamus of rats while they engaged in feeding behavior or received drug treatments used to treat feeding disorders and affective disorders in humans. Hypothalamic serotonin increased significantly relative to controls in response to (1) intraperitoneal tryptophan after food deprivation, (2) the smell of food and eating a meal, (3) a conditioned taste aversion, (4) d-fenfluramine and fluoxetine, and (5) an amphetamine challenge test after chronic low doses of lithium. In some cases, increases correlated with nonspecific behavioral arousal were seen in the hippocampus. The results suggest that diet, drug, and behavioral therapies, alone or combined, can be used to preferentially modify hypothalamic serotonin in the control of behavioral, emotional, and endocrine problems. PMID- 1752858 TI - Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. AB - The serotonergic neurons of the mammalian brain comprise one of the most expansive chemical systems known. The cell bodies are largely confined to the midline (raphe) region of the brain stem in two general clusters: a superior group that consists of the dorsal raphe nucleus (B-7 and B-6), median raphe nucleus (B-8 and B-5), caudal linear nucleus (rostral B-8), and supralemniscal nucleus (B-9), and an inferior group that consists of nucleus raphe obscurus (B 2), nucleus raphe pallidus (B-1), nucleus raphe magnus (B-3), ventral lateral medulla (B-1/B-3), and the area postrema. The axons from these cells project throughout the neuroaxis from the spinal cord to the olfactory bulb and from the cerebral cortex to the hypothalamus. The development of this giant system begins very early in gestation and is influenced by a variety of growth regulatory factors, including the astroglial protein S-100 beta. Evidence will be presented that the serotonergic system plays a major role in the maturation of the brain by interacting with the 5-HT1A receptors which are most dense during these early developmental periods. The 5-HT1A receptor is located on both neurons and astrocytes, and in the latter cells may serve to stimulate release of S-100 beta. The developmental role of 5-HT appears to become dormant as the brain matures, and during aging and Alzheimer's disease, 5-HT receptors are significantly depressed. However, specific damage to 5-HT fibers in the adult brain by 5,7 dihydroxytryptamine produces a sharp fall in the levels of 5-HT which seems to reactivate the developmental signals in the brain. Not only are the serotonergic fibers encouraged to sprout and expand their territory, but the stimulation of the astrocytic growth factor by a 5-HT1A agonist is reinstated. The ability to recall developmental processes in the adult brain by interrupting the 5-HT fibers may provide important tools for understanding and treating the aged brain. PMID- 1752859 TI - Serotonin activity in anorexia and bulimia nervosa: relationship to the modulation of feeding and mood. AB - Brain serotonin activity contributes to satiety. Theoretically, binging behavior is consistent with reduced serotonin function, whereas anorexia nervosa is consistent with increased serotonin activity. Brain serotonin abnormalities could also contribute to psychopathologic behaviors such as dysphoric mood, disturbance of impulse control, and obsessionality, as well as neuroendocrine disturbances. In fact, disturbances of serotonin have been found in acutely ill anorexia nervosa patients. Tryptophan, an essential amino acid found in the diet, is the precursor of serotonin. Thus serotonin disturbances could be secondary to dietary abnormalities. However, disturbances of serotonin activity appear to persist after long-term weight recovery from anorexia nervosa. While speculative, it is possible that increased serotonin activity could contribute to the pathogenesis of restricted eating and obsessional behaviors in this illness. Physiologic and pharmacologic evidence suggest that patients with normal weight bulimia have reduced serotonin activity when acutely ill. Such disturbances, even if secondary to dietary abnormalities, may still contribute to dysphoric mood and binging behavior. PMID- 1752860 TI - Opportunities for treatment of psychoactive substance use disorders with serotonergic medications. AB - The authors review both the preclinical and the clinical evidence for a role of serotonin (5-HT) systems in the regulation of drug-taking behavior. Animal studies show that pharmacologic treatments that enhance 5-HT function, notably selective reuptake inhibitors, reduce the self-administration of a variety of substances of abuse, including ethanol and cocaine. These treatments also tend to suppress consummatory behavior in general. In contrast to the broad spectrum of suppression following 5-HT enhancement, selective antagonists at the 5-HT3 receptor subtype have been reported to reduce ethanol but not cocaine or food intake. Although essentially limited to alcohol abusers, clinical studies seem to support the preclinical findings that a number of 5-HT reuptake inhibitors decrease interest in and intake of alcohol in mild-moderate ethanol-dependent individuals. Furthermore, other serotonergic drugs may show utility in the treatment of alcohol abuse. Another way in which serotonergic medications can be used in treating substance abuse is by the treatment of comorbid psychoactive illness for which such drugs are already known to be effective, e.g., depression and anxiety disorders. PMID- 1752861 TI - Serotonin uptake inhibitors: effects on motivated consummatory behaviors. AB - Within the context of the role of serotonin (5-HT) in motivated behavior, the authors examine the effects of 5-HT uptake inhibitors on the regulation of motivated consummatory behavior. Emphasis in this field has for the most part focused on the consistent observation that treatment with these agents attenuates voluntary ethanol drinking behavior in both rats and humans. There has been extensive speculation that the underlying mechanism of the decrease in ethanol intake induced by 5-HT uptake inhibition may involve a modulation of ethanol's reinforcing properties. However, increasing evidence indicates that food consumption and fluid intake are also attenuated by these compounds. In addition, it has been shown that morphine, amphetamine, cocaine, and nicotine self administration, as well as intracranial self-stimulation, are all decreased following 5-HT uptake inhibition. These observations support strongly the notion that the effects of these agents are global in nature and not specific to any single consummatory behavior. They also suggest that 5-HT uptake inhibition may result in nonspecific modification of motivated behavior in general. PMID- 1752862 TI - A biomechanical model for the analysis of the cervical spine in static postures. AB - To gain a better understanding of the forces working on the cervical spine, a spatial biomechanical computer model was developed. The first part of our research was concerned with the development of a kinematic model to establish the axes of rotation and the mutual position of the head and vertebrae with regard to flexion, extension, lateroflexion and torsion. The next step was the introduction of lines of action of muscle forces and an external load, created by gravity and accelerations in different directions, working on the centre of gravity of the head and possibly a helmet. Although the results of our calculations should be interpreted cautiously in the present stage of our research, some conclusions can be drawn with respect to different head positions. During flexion muscle forces and joint reaction forces increase, except the force between the odontoid and the ligamentum transversum atlantis. This force shows a minimum during moderate flexion. The joint reaction forces on the levels C0-C1, C1-C2, and C7-T1 reach minimum values during extension, each in different stages of extension. Axial rotation less than 35 degrees does not need great muscle forces, axial rotation further than 35 degrees causes muscle forces and joint reaction forces to increase fast. While performing, lateral flexion muscle forces and joint reaction forces must increase rapidly to balance the head. We obtained some indications that the order of magnitude of the calculated forces is correct. PMID- 1752863 TI - A three-dimensional analysis of a bioprosthetic heart valve. AB - A three-dimensional finite element model of the leaflets of a bicuspid bioprosthetic heart valve is presented. The model is based on a non-linear elastic representation of the tissue behaviour which closely simulates that found in experiments. The geometry of the model is based on measurements from a real valve. Shell elements which permit bending have been used in the analysis. The results indicate that bending stresses in the leaflets make a significant contribution to their deformation. This confirms earlier two-dimensional work which had suggested that analyses, where only membrane stresses were modelled, were likely to produce significant errors in the stress states. The analysis also predicts peak stresses close to, but not at, the attachment of the leaflet to the stent post. PMID- 1752864 TI - Mechanical properties of trabecular bone. Dependency on strain rate. AB - The effect of strain rate (epsilon) and apparent density (rho) on stiffness (E), strength (sigma u), and ultimate strain (epsilon u) was studied in 60 human trabecular bone specimens from the proximal tibia. Testing was performed by uniaxial compression to 5% specimen strain. Six different strain rates were used: 0.0001, 0.001, 0.01, 0.1, 1, and 10 s-1. Apparent density ranged between 0.23 and 0.59 g cm-3. Linear and non-linear regression analyses using strength, stiffness and ultimate strain as dependent variables (Y) and strain rate and apparent density as independent variables were performed using the following models: Y = a rho b epsilon c, Y = rho b(a + c epsilon; Y = (a + b rho)epsilon c, Y = a rho 2 epsilon c, E = a rho 3 epsilon c. The variations of strength and stiffness were explained equally well by the linear and the power function relationship to strain rate. The exponent was 0.07 in the power function relationship between strength and strain rate and 0.05 between stiffness and strain rate. The variation of ultimate strain was explained best using a power function relationship to strain rate (exponent = 0.03). The variation of strength and stiffness was explained equally well by the linear, power function and quadratic relationship to apparent density. The cubic relationship between stiffness and apparent density showed a less good fit. Ultimate strain varied independently of apparent density. PMID- 1752865 TI - The viscoelastic responses of the human cervical spine in torsion: experimental limitations of quasi-linear theory, and a method for reducing these effects. AB - The dynamic torsional viscoelastic responses of the human cadaver cervical spine were measured in vitro. The quasi-linear formulation of time dependent behavior was used to describe and predict the resultant torque as a function of applied angular deflection and time. The performance of the quasi-linear model was good, reaching correlation at the 99% confidence level; however, it tended to underestimate hysteresis energy (mean relative deviation = -19.1%) and observed stiffness. This was in part due to difficulties in establishing the physical constants of the quasi-linear model from finite rate relaxation testing. An extrapolation deconvolution technique to enhance the experimentally derived constants was developed, to reduce the detrimental effects of finite rate testing. The quasi-linear model based on this enhanced derivation showed improved predictive ability and hysteresis energy determination. PMID- 1752866 TI - Freezing for postmortal storage influences the biomechanical properties of linear skin wounds. AB - Specimens for biomechanical investigations are often stored frozen between sampling and testing. Several authors have analysed the effects of freezing on a variety of intact tissues; while some have found mostly minor changes, others have reported no adverse effects. Healing wounds contain more fragile tissue components than other tissues and are therefore more sensitive to possible adverse effects. This study on rat skin wounds (healed for 10 and 20 days) demonstrates that freezing has a significant adverse influence on the mechanical properties. It is concluded that fresh tissue should be used whenever possible. In case storage in a freezer is necessary great care should be taken when designing the experimental protocol. PMID- 1752867 TI - Application of homogenization theory to the study of trabecular bone mechanics. AB - It is generally accepted that the strength and stiffness of trabecular bone is strongly affected by trabecular microstructure. It has also been hypothesized that stress induced adaptation of trabecular bone is affected by trabecular tissue level stress and/or strain. At this time, however, there is no generally accepted (or easily accomplished) technique for predicting the effect of microstructure on trabecular bone apparent stiffness and strength or estimating tissue level stress or strain. In this paper, a recently developed mechanics theory specifically designed to analyze microstructured materials, called the homogenization theory, is presented and applied to analyze trabecular bone mechanics. Using the homogenization theory it is possible to perform microstructural and continuum analyses separately and then combine them in a systematic manner. Stiffness predictions from two different microstructural models of trabecular bone show reasonable agreement with experimental results, depending on metaphyseal region, (R2 greater than 0.5 for proximal humerus specimens, R2 less than 0.5 for distal femur and proximal tibia specimens). Estimates of both microstructural strain energy density (SED) and apparent SED show that there are large differences (up to 30 times) between apparent SED (as calculated by standard continuum finite element analyses) and the maximum microstructural or tissue SED. Furthermore, a strut and spherical void microstructure gave very different estimates of maximum tissue SED for the same bone volume fraction (BV/TV). The estimates from the spherical void microstructure are between 2 and 20 times greater than the strut microstructure at 10-20% BV/TV. PMID- 1752868 TI - The constitutive behaviour of passive heart muscle tissue: a quasi-linear viscoelastic formulation. AB - A quasi-linear viscoelastic law with a continuous relaxation spectrum describing triaxial constitutive behaviour of heart muscle tissue is presented. The elastic response of the viscoelastic law is anisotropic, while the relaxation behaviour is assumed isotropic. The law is designed for a biphasic description (fluid solid) of the myocardial tissue. Biaxial and uniaxial stress-strain curves from the literature are used to evaluate the parameters of the model. The non-linear elastic response, the difference between fibre and cross-fibre stiffness, the phenomenon of stress relaxation, the stiffening of the stress-strain relationship with increasing strain rate and the weak frequency dependency of the dissipated energy during cyclic loading are fairly well described by the proposed law. However, it is found that the model produces realistic values for the dissipated energy during cyclic loading only when relaxation parameter values are chosen which result in an overestimation of the stress relaxation data by more than 100%. This finding may indicate non-quasi-linearity of viscoelasticity of passive heart muscle tissue. PMID- 1752869 TI - A conductive polymer sensor for measuring external finger forces. AB - This paper describes the construction and use of a durable and thin force sensor that can be attached to the palmar surface of the fingers and hands for studying the biomechanics of grasp and for use in hand injury rehabilitation. These force sensors were constructed using a modified commercially available conductive polymer pressure sensing element and installing an epoxy dome for directing applied forces through a 12 mm diameter active sensing area. The installation of an epoxy dome was effective for making the sensors insensitive to contact surfaces varying from 25 to 1100 mm2 and a 16 mm radius surface curved convex towards the finger. The completed sensors were only 1.8 mm thick and capable of being taped to the distal phalangeal finger pads. They were calibrated on the hand by pinching a strain gage dynamometer. The useful range was between 0 and 30 N with an accuracy of 1 N for both static loading and normal dynamic grasp activities. The sensor time constant was 0.54 ms for a step force input. Because of varying offset voltages every time the sensors were attached, these sensors should be calibrated on the hand before each use. The sensors were used for measuring finger forces during controlled pinching and lifting tasks, and during ordinary grasping activities, such as picking up a book or a box, where the useful force range and response for these sensors were adequate. PMID- 1752870 TI - Non-interacting modes for stress, strain and energy in anisotropic hard tissue. AB - The six non-interacting modes for stress, strain and energy in an orthotropic elastic model of human femoral cortical bone tissue are discussed and illustrated. The stress and strain modes are illustrated using the representation of the stress and strain fields around a circular hole in a flat plate of cortical bone subjected to a uniaxial field of tension as the example. The six modes play a role in the stress analysis of orthotropic elastic materials similar to the roles played by the hydrostatic and deviatoric non-interacting stress, strain and energy modes in isotropic elasticity. The biomechanical significance of the six non-interacting modes for stress, strain and energy in hard tissue is both practical and suggestive. The modes suggest a practical scheme for the representation of stress and strain fields in hard tissue. The existence of the modes suggests physical insights, for example, possible failure mechanisms or adaptation strategies possessed by the hard tissues. PMID- 1752871 TI - Comments on 'The mechanical properties of the rabbit and human cornea'. PMID- 1752872 TI - Comments on 'Estimation of instantaneous moment arms of lower-leg muscles'. PMID- 1752873 TI - Etiology and control of postburn hypermetabolism: the 1991 presidential address to the American Burn Association. PMID- 1752874 TI - The burned patient's response to the environment: the 1991 Everett Idris Evans Memorial Lecture. AB - Homeostatic reflexes are believed to supply the means by which the body adapts to changes in the environment (posture, temperature, etc.) and, hence, it might be expected that their importance would increase when the body is disturbed by trauma. In fact, these reflexes are largely abandoned in the response to danger (the defense-arousal reaction), and it is only after simple fluid loss that a limited improvement is seen, that is, an increase in the sensitivity of the baroreflex. Whenever tissue damage generates nociceptive C fiber afferent impulses, there is serious and relatively long-lasting inhibition of the baroreflex and of all aspects of neural thermoregulation. Significant changes occur after quite moderate injuries and do not depend on any reduction in tissue oxygenation. In children with burns in whom early pyrexia is common, central thermoregulation may also be affected by cytokine pyrogens. These changes have implications for the management of patients with all types of injuries. However, further analysis is needed if we are to understand these responses and their role in the body's defense; without this knowledge, we shall not be able to modulate them effectively. PMID- 1752875 TI - Bactericidal and wound-healing properties of sodium hypochlorite solutions: the 1991 Lindberg Award. AB - Toxic effects of sodium hypochlorite on wound healing elements have been confined to a restricted range of sodium hypochlorite concentrations. We investigated concentrations of sodium hypochlorite for antibacterial activity and tissue toxicity at varying time intervals. We attempted to find the efficacious therapeutic concentration that was both microbicidal and nontoxic. Gram-negative and gram-positive isolates (0.1/ml of 1 x 10(8)/ml) were introduced into various concentrations of buffered and unbuffered sodium hypochlorite solutions for determinations of bactericidal activity at 5-, 10-, 15-, and 30-minute intervals. Concentrations of sodium hypochlorite were 0.25%, 0.025%, and 0.0125%. In vitro assays with fibroblasts at the same concentrations were also performed to determine toxicity at the same time intervals. An in vivo incisional model was also used to determine the effects of sodium hypochlorite therapy on wound healing. Bactericidal effects were observed for concentrations as low as 0.025%. Tissue toxicity, both in vitro and in vivo, was observed at concentrations of 0.25% but not at a concentration of 0.025%. Although concentrations below this level were nontoxic, they were not bactericidal. Therefore a modified "Dakin's" solution at a concentration of 0.025% is therapeutically efficacious as a fluid dressing, since it preserves bactericidal properties and eliminates the detrimental potential on wound healing. PMID- 1752876 TI - Effects of cimetidine on fluid requirement during resuscitation of third-degree burns. AB - Seventy percent body surface area third-degree burns were produced in four groups of six guinea pigs each, after which all were resuscitated with Ringer's lactate solution. Group 1 received 4 ml/kg/%burn. Group 2 received 1 ml/kg/%burn with cimetidine, which was begun at 0.5 hours after burn injury. Group 3 received 1 ml/kg/%burn with cimetidine, which was begun at 1 hour after burn injury. Group 4 received 1 ml/kg/%burn without cimetidine. There were no significant differences among any of the groups in blood pressures or heart rates during the study period. Group 4 showed significantly higher hematocrit values than group 2 at 4 hours after burn injury and thereafter. The cardiac outputs of group 2 were the same statistically as those of group 1. The cardiac outputs of group 3 were significantly lower than those that received cimetidine early (group 2), though still higher than those of the 1 ml control group (group 4) at 4 hours after burn injury and thereafter. At 24 hours after burn injury, the water content of the burned skin of group 2 was significantly lower than that of the other groups. We conclude that in third-degree burns, cimetidine therapy can effectively reduce burn edema and the amount of required resuscitation fluid. Early administration is better than late administration of cimetidine. PMID- 1752877 TI - Reperfusion injury in burned rats after delayed fluid resuscitation. AB - Organ failure from ischemic injury is common in deaths that are due to burn when fluid resuscitation is not performed. Organ perfusion after a delay in resuscitation, however, may induce or even accelerate ischemic organ damage. To study this phenomenon, 40 rats were classified (n = 10) to serve as normal control, burn with no resuscitation, burn with early fluid resuscitation, and burn with delayed resuscitation groups. A modified Walker burn model was used to inflict 50% total body surface area scald burns on the rats. Cellular energy metabolism and tissue water content of several vital organs were measured at 8 hours after burn injury. Adenosine triphosphate, total adenine nucleotides, and energy charge in liver, heart, and kidney tissues were significantly lower (p less than 0.05) with delayed fluid resuscitation compared with early resuscitation. Furthermore, in heart and kidney tissues adenosine triphosphate, total adenine nucleotides, and energy charge were significantly lower in the delayed resuscitation group compared with the group that received no fluid resuscitation. This indicates that heart and kidney tissue are more viable at 8 hours after burn injury, with no fluid resuscitation compared with delayed resuscitation. Water content of lung and muscle tissue were significantly lower (p less than 0.05) in the burn group that received no fluid resuscitation compared with that in early and delayed resuscitation groups. Water content of muscle was significantly greater with delayed resuscitation compared with the early resuscitation group. Results indicate that delayed fluid resuscitation in cases of burn shock may disrupt the cellular energy metabolism in some vital organs and cause skeletal muscle edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752878 TI - Evaluation of erythropoietin levels in the anemia of thermal injury. AB - Thermal injury is associated with an anemia of multifactorial etiology. Erythropoietin is a hormone that increases red blood cell production in response to tissue hypoxia and is now being produced in a recombinant form for treatment of some anemias. How erythropoietin levels change in response to thermal injury has not been adequately investigated to date. We studied 27 patients with burns of 10% to 85% total body surface area by serially measuring hemoglobin, hematocrit, reticulocyte count, and erythropoietin levels. Erythropoietin levels were determined by radioimmunoassay. Measurements were taken at admission, before surgery, and after surgery, or at least weekly for a period of up to 4 weeks. Twenty-five of the patients had a reticulocytopenic anemia by the end of the first postburn week. Twenty-three patients remained anemic throughout the study period. Erythropoietin levels increased appropriately as the patients became anemic. Erythropoietin levels related to hemoglobin in a logarithmic fashion with a correlation of -0.869. No differences were found on the basis of burn size or age. This study indicates that the anemia of thermal injury is associated with reticulocytopenia and an elevation of endogenous erythropoietin. PMID- 1752879 TI - Microbial contamination in allografted wound beds in patients with burns. AB - Microbial wound contamination has been recognized as a cause of autograft skin graft failure. Human cadaver allograft is believed to decrease or control microbial wound contamination, and by its adherence to the wound bed, to indicate a sufficiently low microbial count to allow successful application of autograft. Suboptimal "take" of more fragile cultured skin grafts after removal of adherent allograft led us to reexamine the microbial population of these wound beds. Immediately before autografts were placed, wound beds beneath adherent allograft were biopsied for quantitative microbiologic analysis. Eighty tissue biopsy specimens from 21 patients were examined. No patients had signs of infection or sepsis at the time of biopsy. Fifty-seven percent of all patients had positive cultures beneath adherent allograft skin. Twenty-one percent of all cultures revealed "infected" wound beds (greater than 100,000 colonies per gram), and 30% of all wounds were "colonized" (less than 100,000 colonies per gram). These data suggest that take and vascularization of allograft does not guarantee that a wound bed is free of microbial contamination. PMID- 1752880 TI - The effect of ablation of the preoptic anterior hypothalamus on energy metabolism and plasma catecholamines after burn injury in the rat. AB - Rats with burn injuries demonstrate changes in thermoregulation including an upward shift of the set-point and reference temperatures with no change in sensitivity of the response in heat production to displacement of the temperature of the preoptic anterior hypothalamus. In the present studies, the response in plasma and urinary catecholamines to burn injury after destruction of the preoptic anterior hypothalamus was examined in the rat. Preoptic anterior hypothalamic lesioning impaired the hypermetabolic response to burn injury, and at 22 degrees C, burned lesioned rats were hypothermic. Furthermore, plasma levels and urinary excretion rates for catecholamines were not decreased in burned lesioned rats, but rather showed an inverse relationship with heat production. Burned lesioned rats were capable of maintaining body temperature at an ambient temperature of 28 degrees C. This suggests that a less precise thermoregulation is present in lesioned animals. Rats in which the preoptic anterior hypothalamus has been destroyed have reduced tolerance to burn injury. PMID- 1752881 TI - Ocular changes from electrical burn injuries. A literature review and report of cases. AB - One hundred fifty-nine consecutive patients with high-voltage burns were retrospectively reviewed to determine the ocular sequelae of these injuries. Five patients had ophthalmic changes (two had recurrent iritis, eight had cataracts, two had macular holes, and one had central retinal artery occlusion). All four patients with cataractous changes had characteristic anterior subcapsular opacifications, except for one patient who presented with a dense white opacified lens. All had bilateral lenticular changes in which the denser cataract developed earlier than the contact wound and ipsilateral to it. Central retinal artery occlusion has not been previously reported as a complication of electrical burns. Macular holes, formerly believed to be rare in these injuries, were found in two of the five patients. Ocular complications from electrical burn injuries are uncommon. Although a number of these ocular changes occur immediately after injury, many of the visually impairing changes develop days and even years after a severe electrical burn injury; thus, careful follow-up is mandated. PMID- 1752882 TI - Tumor necrosis factor mediates hypertriglyceridemia during thermal injury in mice genetically susceptible to lipopolysaccharides. AB - A rise in plasma triglycerides has been noted after thermal injury in a number of animal species including humans. In this study we identified a factor, tumor necrosis factor, which was responsible for increased plasma triglycerides during thermal injury that was induced by scalding. Two strains of mice that differed genetically in susceptibility to lipopolysaccharides were used. These were CH3HEB/HeJ (LPS-) and CH3HEB/FeJ (LPS+). A 15% total body surface area was burned; this resulted in an increase of plasma triglycerides of 126% of preburn levels in the LPS+ strain 24 hours after burn injury. No change in triglycerides was noted in the LPS- mice at any time after burn injury. Sera from LPS+ mice at 1 to 2 hours after burn injury was injected into nonburned animals of the same strain; this caused a 62% +/- 5% increase in plasma triglycerides 24 hours after injection. When thermally injured LPS+ mice were injected with anti-tumor necrosis factor-alpha at 1 hour after injury, they did not show a rise in plasma triglycerides at any time between 24 to 72 hours after injury. Hepatic secretion of triglycerides was also measured 1 day after burn; the average secretion of triglycerides was significantly reduced (2.69 +/- 0.36 mg/kg/hr, compared with 3.83 +/- 0.15 mg/kg/hr for the control). We conclude that tumor necrosis factor, a cytokine that inhibits lipoprotein lipase, causes hypertriglyceridemia during thermal injury in spite of a decreased secretion of triglycerides. This is the first report that demonstrates that hypertriglyceridemia that is secondary to thermal injury is induced by tumor necrosis factor. PMID- 1752883 TI - Treatment for depigmentation resulting from burn injuries. AB - A new surgical technique to "repigment" skin that has been depigmented by deep partial-thickness burn injuries has been developed and proven to be successful. Partial-thickness burn injuries frequently heal with pigmentary changes. Occasionally, permanent depigmentation is observed, especially in areas such as the hands and fingers. This article reports our surgical technique and our success in using it to treat depigmentation after burn injuries. This new technique consists of superficial dermabrasion of the depigmented region, followed by transplantation of melanocytes via epithelial grafts. With this technique, 15 separate surgical procedures have been performed on 11 patients. The follow-up period for these patients has ranged from 0.5 months to 94 months, with an average of 14 months. The skin-graft take has been excellent in all patients. The color match ranges from good to excellent. No complications have been observed, and this procedure has consistently and reliably improved the disfigurement from depigmentation after these burn injuries. PMID- 1752884 TI - Immunoglobulin synthesis by cultured lymphocytes from spleen and mesenteric lymph nodes after thermal injury. AB - A 30% burn injury has been previously reported to impair mitogenic response of splenocytes to a B-lymphocyte mitogen and to affect serum levels of serum class specific immunoglobulin. To further investigate the effect of burn injury on the function of B lymphocytes in gut-associated and systemic immune tissues, we studied class-specific immunoglobulin synthesis by cultured lymphocytes from spleen and mesenteric lymph nodes after burn injury in rats. Male Lewis rats received 30% full-thickness burn injuries, and 4 days later, the animals were killed to remove spleen and mesenteric lymph nodes. The cells from spleen and mesenteric lymph nodes were cultured for 5 days with 25 micrograms/ml of lipopolysaccharide. Concentrations of immunoglobulin G (IgG), IgM, and IgA in the supernatant of each well were then measured with enzyme-linked immunosorbent assay for class-specific immunoglobulin. Synthesis of IgG by lymphocytes from spleen was statistically significantly impaired by burn injury (p less than 0.05), but synthesis of IgG by lymphocytes from mesenteric lymph nodes was not affected. There were no significant differences in IgM and IgA synthesis by lymphocytes from spleen between burned animals and controls. The immunoglobulin synthesis in mesenteric lymph nodes did not differ significantly in burned animals compared with controls. The impaired IgG synthesis by lymphocytes from spleen may contribute to increased risk of infection after burn injury. PMID- 1752885 TI - Conservative treatment of scald burns is superior to early excision. AB - Early excision of deep burns has been advocated; however, it is difficult to clinically determine the depth of scald burns during the early postburn period. This prospective, randomized study was designed to determine whether early excision was superior to conservative treatment of scald injuries. Patients with scald injuries (which were not caused by grease) of clinically indeterminant depth were randomized to early (n = 12) or late (n = 12) excision; all patients with obvious superficial and full-thickness injuries were excluded. In the early excision group, all deep wounds were tangentially excised and grafted within 72 hours of admission, whereas in the late treatment group wounds were excised and grafted after 2 weeks had passed since injury. Area excised, postburn day of excision, percent graft take, operating-room time, blood replacement, incidence of infection, and length of hospital stay were compared. No patient experienced a significant wound infection or systemic sepsis. A significantly smaller area of excision was necessary for those patients who were treated with delayed surgery, and concomitant decreases in operating-room time and blood loss were observed. Notably, only one half of the patients who were randomized to the delayed excision group ultimately required surgical intervention to achieve wound closure. Graft take was comparable for both groups, as was length of hospital stay. Early clinical evaluation of scald injuries appears to be equivocal, and later evaluations reveal a less severe injury. Financial gains can be made when surgical excision of scald injuries is delayed until 2 weeks after injury because of a related reduction in hospital expenditures. PMID- 1752886 TI - Stroke prevention during carotid surgery in high risk patients (value of transcranial Doppler and local anesthesia). AB - In a series of 114 cases, carotid surgery was performed under local anesthesia by cervical block in order to assess cerebral status. Preoperative transcranial Doppler was used to select high risk patients for shunting. Intraoperatively brain function was checked by carotid arterial blood pressure monitoring and transcranial Doppler. No stroke occurred during the procedure. Postoperatively two deaths (1.8%) occurred, one due to intracerebral hemorrhage and one to a late myocardial infarct. The predictive value of both transcranial Doppler and stump pressure monitoring for shunting was 97% respectively. In combination, the two methods provided 100% protection. During the same period, 1406 patients underwent carotid surgery under general anesthesia. Carotid surgery stroke can be prevented either by using transcranial Doppler together with carotid stump pressure monitoring when the procedure is performed under general anesthesia or by operating under local anesthesia. PMID- 1752887 TI - Morbidity and mortality following carotid surgery. AB - The records of 920 patients who underwent carotid endarterectomy by the same surgeon (M. D'A) between 1976 and 1989 were reviewed. Particular attention was paid to both the neurological and general complications and to how and when the neurological symptoms appeared. Among these patients, a cumulative stroke plus death rate of 3.1% was observed. Complications were classified as clamping ischemia (2.2%), postoperative embolism (1.5%), postoperative thrombosis (2.4%), and cerebral haemorrhage (0.3%). Two patients (0.2%) died from myocardial infarction. In 3.5% of patients, neurological symptoms were transient. The incidence of clamping ischemia was higher when 40 mmHg was considered as the safety limit of the back-pressure; this incidence fell by raising this limit to 50 mmHg, and introducing, in recent years, SEPs monitoring. Intraoperative monitoring of SEPs, in fact, reduced the neurological complications to 1.4%, while intraoperative angiography reduced the need for intraoperative reoperation from 10% to 2%. The use of antiplatelet drugs and an accurate surgical technique are useful steps in the prevention of postoperative embolism or thrombosis. PMID- 1752888 TI - Results of carotid endarterectomy in patients 75 years of age and older. AB - From April 1980 to September 1989, 69 patients over 75 years of age (mean 78 years, range 75 to 86) underwent 81 carotid endarterectomies. Twenty three percent were asymptomatic, 56.5% had symptoms appropriate to lesion location and 20.5% had a non hemispheric syndrome. Nine patients required an associated procedure (combined cardiac surgery 6 pts; vascular surgery 3 pts). Perioperative mortality was 3.7%. The combined early lethal and non lethal stroke rate was 6.1%. Actuarial survival, at 10 years, was 58.4% +/- 10, and the incidence of freedom from stroke at 10 years was 86.2% +/- 5. Despite the fact that the hospital mortality of patients over 75 years undergoing carotid endarterectomy is more than three times that of patients operated on under 75 years of age (1.2%), the combined stroke and neurologic mortality rate is similar to that of patients under 75 years (5.3%). Carotid surgery in patients over 75 years of age does not increase life expectancy but does improve the quality of survival which depends mainly on cardiac events. PMID- 1752889 TI - Inflammatory abdominal aortic aneurysms: does an early stage exist? AB - Inflammatory aneurysms are characterised by a peculiar clinical (i.e. abdominal lumbar pain, weight loss and increased ESR) and morphological picture (whitish wall, adhesion to the surrounding organs and thickness greater than 0.5 cm). The lymphomonoplasmacellular infiltrate and the interstitial deposits of collagen define the histological picture of these lesions. The authors describe three abdominal aortic aneurysms macroscopically characterised by parietal edema, hyperemia and hypertrophy of the preaortic lymphnodes. Histological study revealed a conspicuous and widespread lymphomonoplasmacellular infiltrate and interstitial edema. The abdominal-lumbar pain, the increase in ESR and the reactive C protein defined the clinical and laboratory aspects. Serological tests for syphilis, rheumatoid arthritis and lupus erythematosis were negative. The question which arises from these observations is whether these forms represent separate entities or an early stage in the evolution of inflammatory abdominal aortic aneurysms with fibrosis. PMID- 1752890 TI - Randomized placebo-controlled, double-blind trial of ketanserin in treatment of intermittent claudication. AB - Ketanserin, a selective serotonin (5-HT) antagonist at 5-HT2 receptors, was investigated in a 12-month, double-blind placebo-controlled study in 35 patients with intermittent claudication. Benefit was assessed by repeated treadmill tests, recording claudication distance, and by measurement of Doppler ankle-brachial pressure indices (ABPI) and pulse volume recordings (PVR). Improvement in claudication distance of 42-44% was noted during the 12 months of the double blind study and this trend continued to 53-67% during an additional 3 month run out period on placebo. There were no significant differences between the group given Ketanserin and the placebo group. The hemodynamic measurements demonstrated no statistically significant change in either ABPI or PVR throughout the study period, and no significant differences between the two groups. The conclusion of the study indicates that Ketanserin is ineffective in the treatment of intermittent claudication. PMID- 1752891 TI - 99mTc-HSA lymphoscintigraphy and leg edema following arterial reconstruction. AB - Twelve patients with peripheral arterial occlusive disease were evaluated prospectively in an effort to further investigate the etiology of pedal and lower leg edema that occurs following revascularization (e.g., aorto-iliac or femoropopliteal bypass). Serum total protein, albumin, blood urea nitrogen, and creatinine levels were measured (in addition to peripheral venous pressure), and lymphoscintigraphy of the lower leg was performed. These parameters were assessed just prior to surgery, four weeks postoperatively, and again at follow-up. The serum levels obtained four weeks after surgery and on subsequent follow-ups were significantly higher than the preoperative values. Preoperative peripheral venous pressure was not significantly different from that obtained after surgery. There was no correlation between these pressure measurements and the degree of edema (Grades I to IV correspond to increasing degrees of severity). For both the supine and upright positions, lymphoscintigraphic counts in the inguinal region were significantly higher after surgery. However, the relative increase was dependent upon the severity of edema. The postoperative lymphoscintigraphic count in the upright position was 77 +/- 33 CPS in patients with Grades I and II edema (n = 6) and 20.6 +/- 16.2 CPS in patients with Grades III and IV edema (n = 10) (p less than 0.01). Thus, a lesser degree of postoperative pedal and lower leg edema was associated with higher lymphoscintigraphic counts. We conclude that major contributors to the development of lower extremity edema following arterial reconstruction are failed capillary hydrostatic pressure and interrupted lymphatic drainage. PMID- 1752892 TI - Intravenous digital subtraction angiography in the management of peripheral vascular disease. AB - All patients undergoing peripheral injection intravenous digital subtraction angiography (ivDSA) for peripheral vascular disease during 1987 have been reviewed (140 patients). The radiological distribution of disease was aorto-iliac occlusive (AI) 36 (23%), femoropopliteal (FP) 68 (44%), mixed AI/FP 36 (23%). Clinical diagnosis was correct for AI disease in 92%, for FP disease in 65% and for mixed AI/FP disease in 47%. ivDSA was the only investigation required for management in 111 of all 140 patients (79%), and in 33 of the 36 patients with AI disease (92%), but was less accurate in defining femoropopliteal disease, 22 patients (32%) requiring additional arteriography. Conventional arteriography was performed in 200 patients in 1982 compared with 100 in 1987. ivDSA is particularly suitable for the investigation of AI disease, a condition which is accurately detected by clinical examination, with a reduction in morbidity and bed occupancy. PMID- 1752893 TI - Major stump trauma following below-knee amputation. Outcome and recommendations for therapy. AB - Injury to the stump of a below-knee amputation (BKA) may require revision to a higher level of amputation. We undertook a retrospective review of BKAs performed during a 14-year period. Twenty-three patients suffered trauma to their stumps. Most (80%) trauma resulted from a fall. The severity of the trauma was graded on a three-part scale. Operative reclosure was attempted in 8 cases with 2 successes. Closure by secondary intent was successful in 7 of the 12 attempts. A total of 11 patients had revision to above-knee amputation (AKA) as the final outcome. The severity of trauma correlated inversely with the likelihood of eventual stump salvage. We conclude that primary reclosure or closure by secondary intent should be considered, since in 53% of attempts this results in knee preservation. Analysis of noninvasive vascular testing prior to the BKA was not helpful in predicting successful salvage of traumatized stumps. PMID- 1752894 TI - A self-retaining retractor for improved exposure of the infrarenal abdominal aorta. AB - A simple method of achieving better exposure of the infrarenal abdominal aorta during aortoiliac surgery is reported. Once the aorta is exposed, the peritoneum, retroperitoneal fat and the inferior vena cava are spread by an orthostatic retractor, of a Weilaner type, modified by the author, to meet this particular requirement. PMID- 1752895 TI - The retroperitoneal approach to aortic surgery associated with horseshoe kidney. AB - The horseshoe kidney is a rare anomaly that can significantly complicate aortic surgery. A bulky isthmus, abnormalities of renal anatomy, and a variable blood supply associated with a horseshoe kidney can pose technical difficulties in terms of aortic reconstruction. The left retroperitoneal approach affords an excellent exposure of the abdominal aorta in patients with a horseshoe kidney without dividing the renal isthmus and avoids the risk of injury to a ureter in an anomalous location. This is a case report of a patient with a horseshoe kidney who underwent a successful repair of an abdominal aortic aneurysm by a left retroperitoneal approach. PMID- 1752896 TI - Successful surgical treatment of aneurysm of the suprarenal abdominal aorta. AB - We report the successful surgical resection of a saccular aneurysm of the suprarenal abdominal aorta adjacent to the origin of the superior mesenteric artery. Reconstruction of the superior mesenteric artery with the splenic artery was a useful technique for salvaging the ischemic small intestine. However, successful surgical treatment of this type of aneurysm remains a great challenge. PMID- 1752897 TI - Abdominal aortic coarctation inducing aortic occlusion and renovascular hypertension. AB - Abdominal aortic coarctation is a rare, non-atherosclerotic disease. It is a functionally significant at an early age when associated with aortic branch stenosis and renovascular hypertension. The pathogenesis of aortic constrictive lesions remains unknown, but may be related to developmental error or aortic growth arrest and various hypotheses have been reported. When the renal arteries are involved by the coarctation, severe hypertension is common at an early age and in untreated patients, life-threatening complications commonly occur. Patients who reach the age of 40 years generally have the coarctation below the renal arteries but even when the renal arteries are not involved by the coarctation, renovascular disease may still occur due to secondary atherosclerosis. Aortic thrombosis secondary to abdominal aortic coarctation with renovascular disease and lower limb ischemia, occurring in a 63-year old woman, is reported. PMID- 1752898 TI - A case of congenital hypoplasia of the right external iliac artery. AB - A 18 years male had congenital hypoplasia of the right external iliac artery and thrombosis of its narrowest part. Congenital megacolon, anal atresia and hyposomical nanism were also present. Surgical intervention was indicated because he was developing arterial insufficiency and muscular hypotrophy of the right leg. A bypass was performed with a reversed autogenous vein between the common iliac artery and the common femoral artery. PMID- 1752899 TI - Giant retroperitoneal pelvic hemangiopericytoma. AB - Hemangiopericytoma is a rare soft tissue sarcoma, comprising less than one percent of all vascular neoplasms. This report describes a 75-year-old man with a very large malignant retroperitoneal hemangiopericytoma that was successfully excised. The tumor measured 23 cm in its greatest dimension and, as such, is the largest malignant hemangiopericytoma reported to date. The clinical and pathologic features of this lesion and a review of the literature are presented. PMID- 1752900 TI - Postlaminectomy arteriovenous fistula: the Brazilian experience. AB - Arteriovenous fistula is an infrequent complication of lumbar disc surgery. It is often not suspected, and the symptoms are diagnosed as deep venous thrombosis or heart failure. As a result of our review of the Brazilian literature and a survey of 3,500 Brazilian physicians, 5 cases of post-laminectomy arteriovenous fistula are added to the literature. A review of these cases shows that: (1) the right common iliac artery was injured in most cases, (2) the vena cava was frequently injured, and (3) direct repair was possible when the vena cava and the aorta were injured. A vascular prosthesis was necessary when the iliac arteries were damaged. The correct diagnosis is usually made by detection of an abdominal bruit in a patient with a history of lumbar disc surgery and is confirmed by arteriogram. Surgical treatment, either by suture or bypass, is the treatment of choice and results in cure. PMID- 1752901 TI - Combined surgical approach to coexistent carotid and coronary artery disease. AB - Combined coronary artery bypass and carotid endarterectomy were performed in 52 patients (mean age 61 years) between 1981 and 1990. Of these, 36 (69%) had functional class III-IV angina pectoris, 33 (63%) had triple-vessel disease, 36 (69%) had one, or more, previous myocardial infarctions, and 33 (63%) had an abnormal left ventricular function. In 4 cases, additional cardiac procedures were performed. Asymptomatic carotid stenosis was documented in 29 patients (56%) and the remaining 23 (44%) had experienced cerebrovascular symptoms. All patients had hemodynamically significant stenosis of at least one carotid artery, 17 (33%) had severe bilateral carotid artery stenosis, and 6 (11%) had an additional occlusion of the contralateral internal carotid artery. There were no early deaths. Perioperative morbidity included: myocardial infarction in 4 patients (7.7%) and neurological deficit in 3 (5.7%) but functional impairment was not permanent. Late results have been obtained for all 52 patients at a mean postoperative interval of 35 months. Four patients (7.7%) have died, and the 5 year life-table survival rate was 83%. At five years, actuarial curves showed 67% of patients to be free of all serious events or death. Late mortality and morbidity were related above all to the progression of the coronary artery disease. We concluded that simultaneous endarterectomy of significant carotid artery stenosis in candidates for coronary bypass can be done safely and considered as more practical for the patient. PMID- 1752902 TI - Long term results of cardiac valve replacement in patients aged 75 years and older. AB - From June 1978 to December 1989, 158 patients over 75 years of age (mean: 78 years; range 75 to 86 years) underwent 164 valve replacements: 134 in the aortic, 18 in the mitral and 6 in double mitral and aortic positions. One hundred and seven of these valves (66%) were bioprostheses, 93 aortic and 14 mitral and 57 valves (34%) were mechanical prostheses; 47 aortic and 10 mitral. Hospital mortality (less than or equal to 30 days) was 7% (11 patients, all in NYHA class III or IV) but was higher in patients who had undergone associated procedures (9.8%; 6/61 patients) or in patients who had mitral valve replacements (11%) and in double valve replacement (16.6%). Because of a minimal delay of one year, long term follow-up information (100%) was only obtained from the first 110 patients discharged from hospital. Late mortality has been 13.6% and actuarial survival at 11 years was 71.5% +/- 5. Therefore, despite a hospital mortality of more than twice that of patients operated upon under 75 years of age (3.3%), an actuarial survival at 11 years, similar to that of patients under 75 years (77 +/- 5%) and the functional improvement obtained (95% of survivors are NYHA class I or II) certainly justify surgery in these patients. Because of the incidence of anticoagulant related hemorrhages in these patients (1.7% patient year) and since, structural deterioration of the bioprostheses was non existent in this series, a bioprosthesis appears to be the best valvular substitute in patients over 75 years of age. PMID- 1752903 TI - Bioprosthetic valve endocarditis: factors affecting bad outcome. AB - Prosthetic valve endocarditis (PVE) remains an uncommon but serious complication of cardiac valve replacement. We analysed several risk factors (active or healed, early or late endocarditis, congestive heart failure, arterial emboli etc.) in order to identify the factors which may predict bad outcome. The overall mortality rate was 46.8% (15/32 patients). There was a significantly higher mortality rate in patients with early endocarditis (80%) than in those with late endocarditis (38%) (p less than 0.01). In the group of patients who underwent reoperation, the mortality rate was higher in those with active endocarditis (70%) than in those with healed endocarditis (28.5%) (p less than 0.05). We believe that combined medical and surgical treatment is the best management for bioprosthetic valve endocarditis, with the institution of appropriate preoperative antibiotic therapy, to attempt to achieve sterilization. PMID- 1752904 TI - Clinical results with the Biocor porcine bioprosthesis. AB - In order to evaluate our clinical results with the use of the Biocor prosthesis, a total of 1,101 patients were studied. Follow-up was from 1 to 96 months (mean 48); cumulative follow-up in the aortic group (385 patients) was 1,230 patient years and in the mitral group (716 patients) 3,018 patient years. Mitral patients had 102 late complications (14.24%), and aortic patients had 51 (13.2%). A total of 220 patients were under 20 years of age (176 mitral, 44 aortic). Intrinsic valve failure in this subgroup was found in 43% of mitral patients and 29% of aortic patients. Prosthetic endocarditis was more frequent in the aortic group (45%) than in the mitral group (29.9%). Sixty-two patients were reoperated, with a hospital mortality of 12.6%. Reoperation was more frequent in the mitral group and in patients under 20 years of age. The actuarial curve free mortality related to the bioprosthesis was 97.1% (32 patients). At the 8-year follow-up, 96.9% of the aortic versus 95.2% of the mitral group were free of valve dysfunction, and the majority were in Classes I or II of the New York Heart Association (NYHA) classification. The incidence of reoperation, although significant, is acceptable, especially since the bioprosthesis offers a safer alternative than mechanical prostheses followed for similar periods. Analysis of our results suggests the need for continued research for an ideal bioprosthesis. PMID- 1752905 TI - Epilepsy and cardiac surgery. AB - The complex and sometimes severe metabolic, haemodynamic or blood modifications induced by cardio-pulmonary bypass (CPB), can result in alteration of cerebral electrogenesis and even in epileptic paroxyms. Nineteen epileptics (EP) and 41 risk patients (PR), 31 with a family history of epilepsy (FHE) and 10 prone to epilepsy (PPE) were operated upon under CPB; 6 of the EP and 2 of the PPE had abnormal but no paroxymal EEG features during operation. None of the other EP or PR showed any epileptic abnormalities. It seems that normothermia, light haemodilution and elimination of neuroleptic drugs for analgesia prevent per and post-operative epileptic paroxysms. PMID- 1752906 TI - Failure of cryopreserved saphenous vein allografts following coronary artery bypass surgery. AB - Internal mammary arteries and saphenous vein grafts are the most satisfactory conduits for coronary artery bypass. However, at times these conduits are not available, due to previous use or poor quality. This paper reports our experience with 6 patients who underwent coronary artery bypass operations using 10 cryopreserved saphenous veins and internal mammary arteries. Postoperative graft patency was assessed with ultra fast computed tomography or cardiac catheterization. At operation, venous graft patency was 100% (10/10), at 1-8 weeks was 60% (6/10), and at 6-30 months was 0% (0/9). Alternately, all seven internal mammary artery grafts were patent at 2 to 18 months following surgery. One patient died 6 months following operation. Poor graft patency may be related to destruction of the cellular components or fibrosis resulting from the cryopreservation process or from immunologic factors. Because of poor patency compared to autologous conduits, we conclude the use of cryopreserved saphenous veins for coronary artery bypass should be severely restricted. PMID- 1752907 TI - Cardiac myxomas: results of surgical treatment. AB - Nineteen patients with cardiac myxoma were seen at Allegheny General Hospital from November 1974 to December 1990. Eighteen underwent operative removal, 9 females and 9 males; age range was 29-81 (mean 55). There were 18 operations for removal of a total of 24 myxomas. Fifteen patients had single myxomas and 3 had multiple myxomas. Of the 3 patients with multiple myxomas, 2 were familial. One patient had a metastatic recurrence intracranially. Perioperative mortality was 1 of 18 (5.5%). Operative morbidity was 12 of 18 (66.6%). Three patients required permanent pacemakers postoperatively (16.6%). Follow-up is complete and 15 of 17 patients (88%) are alive at a mean follow-up interval of 66.6 months (range 3-196 months). PMID- 1752908 TI - Transesophageal echocardiography in the surgical management of renal cell carcinoma with intracardiac extension. AB - Renal cell carcinomas may extend into the vena cava and the tumor thrombus occasionally involves the right atrium. The operative approach depends upon precise preoperative and intraoperative staging and thrombus localization. We report a case of renal cell carcinoma with complete inferior vena caval and hepatic vein occlusion with tumor extension into the right atrium. Preoperatively, transesophageal echocardiography provided superior images of the tumor and its extension, and intraoperatively allowed continuous monitoring of cardiac function and the removal of tumor from the atrium and inferior vena cava. Its use obviated the need for more costly and invasive preoperative and intraoperative procedures. PMID- 1752909 TI - Mitral valve replacement in a patient with idiopathic thrombocytopenic purpura: preoperative treatment with danazol. AB - A 64-year-old woman with refractory idiopathic (autoimmune) thrombocytopenic purpura required urgent mitral valve replacement. Preoperative therapeutic interventions to raise dangerously low platelet counts were unsuccessful until danazol therapy was institued. Danazol therapy was associated with elevation of the platelet count to greater than 125 x 10(9)/L and allowed successful mitral valve replacement and left atrial thrombectomy to be performed. Postoperative bleeding was average and blood product replacement was not excessive. This case of mitral valve disease in a patient with idiopathic (autoimmune) thrombocytopenic purpura is unique, because perioperative hemostasis was accomplished using danazol and splenectomy was not required. PMID- 1752910 TI - Professional oaths--pharmacy can lead the way. PMID- 1752911 TI - Holism. PMID- 1752912 TI - The stability of four catecholamines in 5% glucose infusions. AB - The stability of adrenaline, noradrenaline, dopamine and dobutamine in 5% glucose infusion minibags stored at 5 degrees C was determined. Results indicated that noradrenaline (16 and 40 mg/l) and dobutamine (1 and 5 g/l) were relatively stable with t/95% values in excess of 30 days. Adrenaline and dopamine were less stable. The t/95% values were approximately 20 and 14 days respectively. PMID- 1752913 TI - Stability of cefuroxime axetil in suspensions. AB - Cefuroxime axetil is a mixture of two equally active isomers (50% each). A stability-indicating high-pressure liquid chromatography method for the quantification of cefuroxime axetil has been developed. The method is accurate, precise and reproducible. The percentage, relative standard deviation based on six injections was 1.2. Using the developed method, the chemical stability of cefuroxime axetil suspensions has been determined in three vehicles containing sugar and two without sugar. The results varied widely in the vehicles without sugar (up to +/- 31%). In the viscous vehicles containing sugar, the variations in the results were only up to +/- 6%. The cefuroxime axetil in these suspensions was stable up to 28 days when stored at 5 degrees C. In addition, pH values were stable and the physical appearances of the samples did not change. PMID- 1752914 TI - Comparative pharmacokinetics of temazepam Gelthix and liquid-filled soft gelatin capsules. AB - An open, randomized, cross-over study involving 24 healthy volunteers, shows that a novel formulation of temazepam (temazepam Gelthix, TG) in soft gelatin capsules designed to resist i.v. abuse has a similar pharmacokinetic (P-K) profile to that of a liquid-filled, reference formulation (TL) when administered as a single oral dose of 20 mg. The relative bioavailability of the two formulations assessed in terms of the area under the time versus plasma concentration profile (AUC), although statistically different (P less than 0.05), is well within the acceptable 80-120% limits for bioequivalence. Although the mean Cmax for TG (616.6 ng/ml) is lower than for TL (707.9 ng/ml) and the median time to reach Cmax (Tmax) is 40 min (TG) vs. 30 min (TL), there is no significant difference between TG and TL either in their absorption constant (Ka) (0.123 vs. 0.138 min-1 respectively) or their distribution (a) (29.5 vs. 32.4 min) and elimination (beta) (6.3 vs. 6.6 h) half-lives (t1/2). Thus the essential P-K characteristics for the use of temazepam as a hypnotic and premedicant, specifically a rapid rise followed by a prompt fall in blood levels, are conserved by the Gelthix formulation. PMID- 1752915 TI - Captopril and hydrochlorthiazide--a safe antihypertensive for use in general practice? AB - The combination of captopril and hydrochlorthiazide was assessed in 15 hypertensive patients in a general practice setting. The first aim was to determine whether the fall in blood pressure, noted after the first dose of an ACE inhibitor given alone, became unacceptable when the drug was given with a diuretic. The second aim was to assess the impact of the ACE inhibitor on the biochemical abnormalities associated with thiazide diuretic therapy. The drug combination markedly reduced blood pressure but not below 110 systolic after the first dose. In the long-term the treatment significantly lowered blood pressure but did not produce any significant or clinically relevant changes in serum chemistry. PMID- 1752916 TI - Liquid oxygen contaminants--increase in concentration during use of domiciliary liquid oxygen medical systems. AB - The quality of liquid oxygen in domiciliary medical systems used for oxygen therapy was investigated during the emptying cycle under simulated breathing conditions. The increase in the levels of contaminants during the use of these systems was evaluated by gas chromatography and two sampling methods. The quality of liquid oxygen from storage tanks located in hospitals and in the production or in distribution plants was also investigated. PMID- 1752917 TI - Comment on the statistical evaluation of data. AB - This paper represents a plea for a more professional approach to the statistical evaluation of data contained in biological research papers. On the one hand more attention needs to be given to ensuring that statistically rigorous methods are employed; the use of sophisticated methods is now a possibility due to the wide availability of statistical computer packages. Examples are presented of some interesting applications of the multivariate techniques Cluster Analysis and Principal Component Analysis, the data being drawn from early research work into in-vitro fertilization. PMID- 1752918 TI - Anisotropic crystalline microstructures in dendritic arborizations of dried mid cycle cervical mucus: surface morphology and crystallographic study. AB - Studies using scanning electron microscopic techniques permitted characterization of the nature and structure of the anisotropic elements present in dried preparations of mid-cycle cervical mucus. Sodium and potassium sulphates were located in the dehydrated matrix either isolated or bound to the dendrites. Depending on crystallization conditions, they appeared as well-formed individual crystals or as spherulites. PMID- 1752919 TI - Epidermal growth factor in human endometrium: proliferative effects in culture and immunocytochemical localization in normal and endometriotic tissues. AB - Endometrial proliferation is stimulated by oestradiol. The precise mechanism is poorly understood, but may be mediated by epidermal growth factor (EGF). The aim of the present study was to assess the effects of oestradiol and EGF on glandular and stromal proliferation in human endometrial cell cultures, and to determine the localization of EGF-like immunoreactivity (EGF-IR) using immunocytochemistry in normal and endometriotic tissue. Endometrium was obtained from women undergoing curettage or hysterectomy for benign disease, or laparoscopy for endometriosis. For tissue culture experiments, enriched glandular and stromal cells were prepared by digestion with collagenase and DNAase, and cultured for 4 days with oestradiol or EGF, both alone and in combination. Immunocytochemical studies were performed using sheep primary antibody against EGF, with binding visualized using the unlabelled antibody--enzyme method. In combination, oestradiol and EGF increased mean cell counts from 1.15 +/- 0.06 and 1.36 +/- 0.05 x 10(5)/ml to 1.68 +/- 0.1 (+46%) and 1.94 +/- 0.16 (+43%) x 10(5)/ml, in proliferative and secretory gland preparations respectively (n = 10, P less than 0.01). No effect was seen in stromal cell preparations; however the stimulation in gland preparations was further augmented after the addition of stromal conditioned medium. EGF-IR was detected in endometrium from normal women, and in normal and ectopic endometrium from women with endometriosis. EGF-IR was seen in glands and stroma and was not related to the phase of the menstrual cycle. EGF may play a role in the oestrogen-stimulated proliferation of normal and endometriotic endometrium. PMID- 1752920 TI - Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. AB - Circulating levels of luteinizing hormone (LH) are essential for the production of steroid hormones that regulate the timing of ovulation and target tissue responses, as well as maintenance of the corpus luteum and therefore early pregnancy. Clinical and basic science observations show that elevated levels of serum LH during the follicular phase of the menstrual cycle are not only unnecessary for follicular maturation but are deleterious to normal reproductive processes. These elevations may occur as a result of administration of exogenous LH or through an endogenous pathological process (i.e. polycystic ovarian disease, PCOD). Resting levels of LH, synergizing with locally produced IGFs, inhibin and perhaps other growth factors, are adequate for normal follicular growth and steroidogenesis. Elevations in serum LH above these resting levels may result in increased androgen production that diminishes follicular function and reduces early embryo viability. Elevated LH levels during the preovulatory period may also negatively influence post-ovulatory events such as conception and implantation. With these facts in mind, the best results for ovulation induction would be expected with purified follicle-stimulating hormone (FSH) administration to women following gonadotrophin releasing hormone (GnRH) down-regulation. It is hoped that this review provides the reader with an analysis of the complex series of events that regulate normal follicular maturation. The reevaluation of the two cell-two gonadotrophin theory suggests that during the preovulatory period, resting levels of LH are adequate for normal follicular maturation. Indeed, overstimulation of the ovary with excessive amounts of LH may diminish the ability of that target organ to produce fertile ova.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1752921 TI - Salivary progesterone measurements reveal corpus luteum defects which respond poorly to hormonal treatments in operated mild and moderate endometriosis. AB - Thirty-five women who had been operated on for mild or moderate endometriosis were evaluated through 40 menstrual cycles by daily measurements of salivary progesterone concentrations. As controls, 17 women with normal ovulatory cycles and no endometriosis were studied. In the endometriosis group, 22 cycles were unstimulated, seven were stimulated by clomiphene citrate and 11 with clomiphene citrate, human menopausal gonadotrophin and human chorionic gonadotrophin. A variety of aberrations in profiles of salivary progesterone secretion was detected in all the groups of endometriosis patients and the frequency of normal cycles was significantly lower than in controls (14-18% versus 82%, P less than 0.01). The response to the treatments varied greatly within the groups. In conclusion, the present data demonstrate that patients with endometriosis have a variety of defects in the menstrual pattern of salivary progesterone secretion and that their corpus luteum function responds poorly to stimulatory treatments. PMID- 1752922 TI - Clinical use of growth hormone-releasing factor for induction of superovulation. AB - A consistent body of in vivo and in vitro evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in protocols of induction of superovulation gave promising results. In the present study, 10 patients with a previously normal response to gonadotrophins were administered s.c. GH-releasing factor (GRF) combined with gonadotrophins for superovulation induction in an in-vitro fertilization/embryo transfer-gamete intra-Fallopian transfer (IVF/ET-GIFT) programme. Administration of GRF was followed by shortening of the stimulatory cycle and reduction of the total number of gonadotrophin ampoules utilized per patient relative to a previous stimulatory cycle with gonadotrophins alone. A significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately following GRF administration throughout the GRF cycle suggest that GRF supported the ovarian response to gonadotrophins through stimulation of the GH-IGF-I axis. A possible direct effect of GRF is discussed. Before employing GRF for superovulation in infertile patients, the pituitary GH response to provocative stimuli should be evaluated on an individual basis. PMID- 1752923 TI - Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women. AB - Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged. PMID- 1752924 TI - Preovulatory effects of the progesterone antagonist mifepristone (RU486) in mice. AB - The progesterone antagonist mifepristone (RU486), was given in mice once on different days of pregnant mare's serum gonadotrophin-human chorionic gonadotrophin (PMSG-HCG) treatment and its action upon the induction of ovulation studied. RU486 administered on the day after PMSG significantly reduced the ovulation rate. Ovulation was completely inhibited when the progesterone antagonist was given simultaneously with HCG, but RU486 administered 4 h after HCG treatment remained ineffective. The development of two-cell zygotes harvested on day 2 post-coitum from mice treated with RU486 on the day after the PMSG treatment was followed in vitro and showed a significant decrease in the number of embryos developing to blastocysts. These results favour the involvement of progesterone in the ovulation process, indicating a direct effect of this hormone at the ovarian level via a progesterone receptor-mediated action. PMID- 1752925 TI - Evaluation of intrauterine insemination with washed spermatozoa from the husband in the treatment of infertility. AB - In this study, we examined the efficacy of intrauterine insemination with washed spermatozoa from the husband (AIH/IUI) in the treatment of infertility. A total of 127 treatment cycles were completed (1.95 cycles per patient). The indications for AIH/IUI were male subfertility (group I: 53 couples), cervical factor (group II: four couples), male and cervical factor (group III: six couples) and unexplained infertility (group IV: two couples). Sperm washing caused a reduction of the sperm concentration from 52 x 10(6)/ml to 44 x 10(6)/ml (P less than 0.08) and motility from 49% to 45% (P less than 0.03). Twelve pregnancies were achieved (18.5% per couple and 9.5% per cycle): eight pregnancies in group I (15.1%), one in group II (25%) and three in group III (50%). Of the 12 pregnancies, eight occurred in the first insemination cycle, three in the second and one in the third (1.4 cycles/pregnancy). Sperm motility was significantly higher in the pregnant than in the non-pregnant group (65.5% versus 46.4%, respectively; P less than 0.004), whereas no significant difference was observed in the sperm concentration between these two groups (39 x 10(6)/ml and 54 x 10(6)/ml, respectively). In conclusion, AIH/IUI is a technically easy and non-invasive procedure which offers a satisfactory pregnancy rate in selected couples with male subfertility and/or cervical factor infertility. PMID- 1752926 TI - A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination. AB - Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur. PMID- 1752927 TI - Differential distribution of aneuploidy in human gametes according to their sex. AB - The cytogenetic study of human gametes is a new and important source of information because most chromosomal abnormalities originate from meiotic disorders. The frequency and type of abnormalities were analysed in both spermatozoa and mature oocytes. A total of 13,975 human sperm chromosome complements and 1897 oocyte chromosome complements were analysed. In the present study, pooled cytogenetic data on human gametes have been examined to determine and compare the distribution of non-disjunctions in male and female gametes. Human spermatozoa are characterized by a significant excess of hypohaploidy and an equal distribution of aneuploidies among all chromosome groups, whereas mature oocytes display an equal ratio of hypohaploidy to hyperhaploidy and a high variability in the distribution of non-disjunction: in particular, there is a significant over-representation of aneuploidies in both D and G chromosome groups. This indicates that non-disjunction is not a random event in female meiosis and, consequently, that there are differences in the meiotic process between the sexes. Meiotic and environmental factors which could explain the non random malsegregation of chromosomes in female meiosis are discussed. The role of maternal age as a cause of aneuploidy is questioned. PMID- 1752928 TI - Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group. AB - The perinatal outcome and congenital malformations in children born between 1978 and 1987 in Great Britain after in-vitro fertilization (IVF) at Bourn Hall Clinic and the Hallam Medical Centre are presented. The average maternal age was 34.2 years. Multiple births were frequent, constituting 23% of all deliveries; 19% were twins and 4% triplets. There were no quadruplet or higher order multiple births during that period. Twenty-five per cent of all deliveries were preterm. The mean birth weight was 2793 g and was strongly related to multiplicity of pregnancy and gestational age. Overall, 32% of babies had a low birthweight (less than 2500 g) with 6% having a very low birthweight (less than 1500 g). The overall stillbirth and infant mortality rates were two to three times higher than those of infants born after natural conception in England and Wales; this is attributed to the high incidence of multiple births. The stillbirth rates were 5.07, 20.8 and 24.7 per thousand total births in singletons, twins and triplets respectively. The corresponding figures for perinatal mortality were 13.5, 38.2 and 37 per thousand. Overall, 2.5% of the babies had one or more major congenital malformations diagnosed within one week of life. This was within the range of expected values in the United Kingdom and there was no significant increase in any specific malformation. PMID- 1752929 TI - Human sperm capacitation and the acrosome reaction. AB - A model is presented that describes the mechanism of human sperm capacitation and the acrosome reaction. The processes of capacitation and the acrosome reaction are proposed to function in control of the activation/release of acrosomal enzyme(s) involved in sperm penetration through the zona pellucida. During capacitation, the sperm head membranes are biochemically modified, allowing the acrosome reaction to take place when the spermatozoon approaches or reaches the zona pellucida, resulting in the localized activation and release of the appropriate enzyme(s). Further, capacitation is presented as a continuing process that occurs during sperm transport through the female genital tract and is physiologically not completed until the spermatozoon reaches the oocyte (unless the spermatozoa are kept at a particular genital tract site for prolonged periods). The biochemical alterations that occur during capacitation are discussed. It is suggested that extensive modifications in the lipid bilayer structure, e.g. in the cholesterol or phospholipid content, are not part of capacitation because such changes would prematurely destabilize the membranes. Rather, such changes occur during the acrosome reaction. It is also proposed that the human sperm acrosome reaction has many similarities to the somatic cell exocytotic events which occur during the regulated pathway of secretion. One or more oocyte stimuli result in the activation of protein kinases, likely (but not necessarily) via activation of G-protein coupled receptors on the sperm plasma membrane and the formation of second messengers. The kinases phosphorylate and activate proteins, continuing the biochemical cascade that ultimately results in the acrosome reaction. The role of other enzyme systems such as those involved in ion transport, proteolysis, phospholipid metabolism (including that of arachidonic acid) and other metabolic events, is discussed. Calcium ion influx as initiator of the acrosome reaction is reconsidered. The proposed model also takes into consideration the structural events of membrane fusion. PMID- 1752930 TI - Sealed mini-chamber of variable depth for direct observation and extended evaluation of sperm motility under the influence of various gases. AB - A new chamber for microscopical observation of living cells, e.g. spermatozoa, under hermetically sealed conditions and over an extended period is described. Motile spermatozoa were serially observed for several hours and the effect of various gases on sperm motility has been studied. The chamber could also be used to study the effect of various toxic gases in the fields of microbiology and toxicology. PMID- 1752931 TI - Effects of cryopreservation on human sperm acrosomes. AB - Total acrosin activity and acrosomal status were determined before and after cryopreserving human spermatozoa. Three different cryopreservation protocols were used. Both acrosin activity and the incidence of intact acrosomes decreased during cryopreservation. The magnitudes of the decreases were weakly but significantly correlated (r = 0.29, P less than 0.05), suggesting that acrosomal loss contributed to the decrease in acrosin activity. The effects of the three cryopreservation protocols were not significantly different. Motility decreased more (average 43%) than did the percentage of spermatozoa with intact acrosomes (27%) and the total acrosin activity (24%). These measurements suggested that acrosomal damage may have been secondary to cell death. This hypothesis was tested by determining the acrosomal status of spermatozoa that survived cryopreservation. Spermatozoa that were motile after thawing averaged 96% acrosome-intact; their acrosin activity, however, was significantly less than that of motile, unfrozen spermatozoa. These observations support the idea that the acrosomal loss due to cryopreservation is associated with cell death but also demonstrate decreased total acrosin activity of the acrosome-intact spermatozoa that survive cryopreservation. PMID- 1752932 TI - Epididymal sperm aspiration in conjunction with in-vitro fertilization and embryo transfer in cases of obstructive azoospermia. AB - Epididymal sperm aspiration is a new treatment for vasal agenesis. In previous reports, epididymal spermatozoa resulted in pregnancy by utilizing in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT). We sought to investigate the efficacy of epididymal sperm aspiration in conjunction with IVF in patients with congenital absence of the vas deferens or with secondary extended obstruction of spermatic ducts. Fifty-eight attempts were performed in 23 patients (25-50 years). Eight patients (34.7%) had vasal agenesis and 14 (60.8%) presented with vasal secondary extended obstruction. The sperm count was adequate (greater than or equal 20 x 10(6)/ml) in 13.8% of sperm retrievals and sperm motility of 20% was obtained in 15.5% of sperm retrievals. Fourteen attempts at IVF were performed with epididymal sperm counts of 2-44 x 10(6)/ml and motilities of 0-45%. A mean of six mature oocytes (0-13) were inseminated in each case. Five embryo transfers were performed in five patients' wives (35.7%) and two couples had an early pregnancy loss (14.2%). Epididymal sperm aspiration is an advance in treating such patients, as an adequate number of mature spermatozoa can be obtained and used for IVF. However, spermatozoa directly aspirated from the proximal epididymis and with fertilizing capacity in vitro, gave a high rate of embryo degeneration (greater than 50%) after embryo transfer. PMID- 1752933 TI - A comparison of the transient hyperprolactinaemic stress response obtained using two different methods of analgesia for ultrasound-guided transvaginal oocyte retrieval. AB - Transient hyperprolactinaemia has been shown to accompany the procedure of oocyte retrieval under laparoscopic control. This study was concerned with establishing whether transvaginal oocyte retrieval was also associated with hyperprolactinaemia and whether the hyperprolactinaemic response was dependent on the method of anaesthesia/analgesia employed. Two distinct patterns were recorded. Oocyte retrieval under general anaesthesia was accompanied by a rapid rise in prolactin levels, which peaked after 40 min. Oocyte retrieval under intravenous sedation was associated with a slow rise in circulating prolactin concentrations. Significant differences in the prolactin rise between the general anaesthesia and sedation groups appeared within 10 min of the start of the procedure. It is concluded that although the surgical stress of oocyte recovery is associated with mild transient hyperprolactinaemia, most of the hyperprolactinaemic response is due to the anaesthetic. PMID- 1752934 TI - Evaluation of the risk of pelvic infection following transvaginal oocyte recovery. AB - The risk of introducing infection into the peritoneal cavity at the time of transvaginal ultrasound-guided recovery of oocytes in assisted reproduction techniques was assessed by culturing peritoneal fluid samples from 25 women with unexplained infertility. The samples were collected laparoscopically at the time of zygote intra-Fallopian transfer (ZIFT), 24-48 h after oocyte collection. High vaginal and endocervical specimens from 25 women treated by in-vitro fertilization (IVF) and transcervical embryo transfer were cultured for comparison. The peritoneal cultures were negative in all but one patient. High vaginal swabs grew Candida albicans in three cases and endocervical specimens were all negative. Seven and three pregnancies occurred in the ZIFT and IVF groups respectively. No pelvic damage was noted at laparoscopy in those women who had had previous treatment cycles with transvaginal oocyte recovery. This method of oocyte recovery, using prophylactic metronidazole and chlorhexidine for preoperative vaginal preparation, appears to be safe for treatment of women with no previous pelvic damage. PMID- 1752935 TI - Protection from oxidative stress by thioredoxin and superoxide dismutase of mouse embryos fertilized in vitro. AB - A low oxygen tension and superoxide dismutase (SOD) have been demonstrated to promote development of embryos in vitro. In this study, we evaluated the effects of thioredoxin (TRX), a powerful protein disulphide reductase, on the development of mouse embryos fertilized in vitro. Moreover, to clarify the difference between the embryo-protecting mechanisms of TRX and SOD, as well as the critical periods of their actions, we carried out experiments in which we transferred embryos among three different media: basic, TRX- and SOD-supplemented. The rates of 4 cell, blastocyst and expanded blastocyst formation in TRX- (53%, 40% and 34% respectively), or SOD- (59%, 29%, 22%) supplemented media were significantly higher than those (28%, 4%, 0%) in the basic medium. The results of the transfer of embryos using basic and TRX-supplemented media indicated an increase in the rate of expanded blastocysts when TRX was applied from 7 to 30 h, and especially from 18 to 24 h after insemination. In contrast, the results of the transfer of embryos using basic and SOD-supplemented media indicated that SOD, which was also most effective when applied from 7 to 30 h after insemination, had some effects after 30 h. These results indicate that TRX and SOD promote the in-vitro development of mouse embryos fertilized in vitro, which suggests that protection of embryos from oxidative stress is a prerequisite for their development in vitro. SOD and TRX provide protection from oxidative stress by different mechanisms. PMID- 1752936 TI - Human endometrial peptides: a review of their potential role in implantation and placentation. AB - This paper reviews human endometrial peptide synthesis and discusses the biological function of these peptides in relation to implantation and placentation. Despite the substantial literature on quantitative and qualitative peptide synthesis by the endometrium, it has not been possible to define the function of most of these substances. Various aspects of endometrial morphology, especially the endometrial leukocytes, are discussed in an attempt to relate cellular structure and function. A number of serum proteins are produced by the endometrial glandular epithelium and may play a role in early embryo development. Extracellular matrix proteins produced by stromal cells are important for endometrial structure and integrity but also provide a site for trophoblast attachment. Several hormones and binding proteins are also produced by stromal cells and probably influence endometrial metabolism. Complement factors and secretory component may have a role in maintaining a sterile intrauterine environment. Many other endometrial proteins have been less well characterized and their role in endometrial physiology at present remains uncertain. Perhaps the most exciting advance has been the realization that a number of peptide regulatory factors (cytokines and growth factors) are not only produced by the endometrium but play an integral part in the mediation of oestrogen-induced growth and differentiation of the endometrium and with the local metabolic and physiological processes. PMID- 1752937 TI - Risk factors for spontaneous abortion: a case-control study in France. AB - A case-control study was conducted in seven maternity hospitals in the Paris area in 1988 to evaluate the role of several risk factors in spontaneous abortion. A total of 279 cases and 279 controls were compared for socio-demographic characteristics, reproductive history and for conditions of conception. Prior fetal losses [odds ratio (OR) = 2.30 for n greater than or equal to 2; 95% confidence interval (CI) = 1.17-4.61] and maternal age at pregnancy (greater than 30 years) appeared to be major and independent risk factors of spontaneous abortion. Other factors associated with an increased risk of fetal loss were: geographical or ethnic origin (OR = 2.85 for North African women; 95% CI = 1.58 5.10); psychological problems at the time of conception, either related to the outcome of the pregnancy (OR = 3.08; 95% CI = 0.92-10.25) or unrelated to this outcome (OR = 3.35; 95% CI = 1.41-8.00). The following factors were not associated with spontaneous abortion: gravidity, parity, prior induced abortion, prior sexually transmitted diseases and Chlamydia trachomatis serology, menstrual cycle abnormalities, induced conception cycle and in-vitro fertilization, cigarette smoking, current or past use of combined oestrogen/progestagen pill or intrauterine device. These findings confirm the importance of two risk factors for fetal loss: maternal age and number of prior spontaneous abortions. Two risk factors, ethnic origin and psychological problems at the time of conception are also identified, which require further study. PMID- 1752938 TI - P29, an oestrogen receptor-associated protein, is down-regulated by mifepristone in first trimester human placenta and decidua. AB - P29 is an oestrogen receptor-associated protein which acts as a marker of oestrogen action in several systems. The concentration of P29 was measured in placenta and decidua from women following medical termination of pregnancy with the antiprogesterone steroid mifepristone (RU 38,486) and a prostaglandin E1 analogue, and compared with the concentration of P29 found in matched controls undergoing surgical aspiration of pregnancy. Oestrogen receptors were also measured in the same samples. Placental and decidual P29 concentrations (IU/mg protein) in patients treated with mifepristone were 9.6 (4.6-54) and 4.8 (1.3 13.3) (median and range), respectively. These values were significantly lower than the corresponding values, 39.5 (27-69) and 22.0 (2-107) in the surgical group. In contrast, the levels of oestrogen receptors did not change significantly in either decidua or placenta. These data show that mifepristone causes down-regulation of P29 in placenta and decidua, and therefore its action may disrupt oestrogen function in uterine tissues. PMID- 1752939 TI - Long-term use of copper-releasing intrauterine devices for contraception. PMID- 1752940 TI - Role of oxidized low density lipoprotein in atherogenesis. AB - Evidence to support an important role of oxidative modification in mediating the atherogenicity of LDL continues to grow. New hypotheses suggest mechanisms by which Ox-LDL or products of Ox-LDL can affect many components of the atherogenic process, including vasomotor properties and thrombosis, as well as lesion initiation and progression itself. These ideas suggest new approaches, that in combination with lowering of plasma cholesterol, could lead to the prevention of atherosclerosis and its complications. PMID- 1752941 TI - Detection of pre-C and core region mutants of hepatitis B virus in chronic hepatitis B virus carriers. AB - We analyzed the pre-C and core region of hepatitis B virus (HBV) DNA by a polymerase chain reaction in 22 chronic carriers. In 9 hepatitis B e antigen positive asymptomatic carriers, a single DNA band was detected at the expected size, whereas additional shorter DNA bands were observed in 7 out of 11 patients with chronic hepatitis. The smaller-sized DNAs from one chronic hepatitis patient had various lengths of deletions spanning from 105 to 183 bp in the middle of the core gene, and all deletions included common nucleotide sequences. All of the smaller-sized DNAs from the other patients proved to be variant core genes. They were deleted in similar regions by Southern analysis using oligonucleotide probes. A follow-up study revealed that four out of seven chronic hepatitis patients with a short core gene seroconverted to antibody to hepatitis B e antigen, but those with only a "wild type" did not. In another set of sequence studies, clones isolated from two chronic carriers displayed heterogeneity of the pre-C and core gene which was more often present in sera with normal alanine aminotransferase levels than with abnormal levels. These results suggest that mutant HBV alters the host immune response, and may modulate the clinical course of HBV infection. An alternative possibility is that chronic hepatitis selects for mutant forms. PMID- 1752942 TI - Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis. AB - Neutrophil migration into the airspaces of the lung is thought to contribute to the alveolar damage and subsequent fibrosis in idiopathic pulmonary fibrosis (IPF). Interleukin 8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic and activating properties towards neutrophils and thus may contribute to the pathogenesis of IPF. The objective of this investigation was to quantify the spontaneous expression of IL-8 transcripts by alveolar macrophages from normal healthy volunteers and individuals with IPF. A quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction was utilized. The level of IL-8 mRNA in alveolar macrophages was found to be significantly elevated in individuals with lone IPF or with lung fibrosis associated with connective tissue disorders compared to normal healthy controls. Moreover, the level of IL-8 mRNA in the 23 individuals with IPF correlated with the number of neutrophils per milliliter in their bronchoalveolar lavage (BAL) and with the degree of disease severity. In addition, the level of IL-8 protein in BAL was found to reflect the pattern of IL-8 mRNA expression by alveolar macrophages. These data suggest that IL-8 derived from alveolar macrophages may significantly contribute to neutrophil involvement in the pathogenesis of IPF. PMID- 1752943 TI - An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide. AB - Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the V kappa II gene A2. To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the V kappa IIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies. This MAb inhibited Hib PS binding but did not react with Ig isotypic determinants. The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS. HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti Hib PS antibodies having V kappa IIA2 L chains. In contrast, 0 of 10 anti-Hib PS antibodies having either V lambda, V kappa I, or V kappa III chains expressed HibId-1. Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS V kappa IIA2 L chains but not with H chains or other L chains, indicating that the HibId-1 determinant is localized to the V kappa IIA2 chain, and does not require pairing with H chain for expression. Anti-Hib PS antibodies bearing HibId-1 were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS. HibId-1 expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT. HibId-1 was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells. These data demonstrate that antibodies bearing HibId-1/V kappa IIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny. PMID- 1752944 TI - The terminal complement proteins C5b-9 augment binding of high density lipoprotein and its apolipoproteins A-I and A-II to human endothelial cells. AB - Terminal complement protein complexes C5b-9 have been found in human atherosclerotic lesions. Insertion of C5b-9 in the endothelial cell membrane alters permeability, induces membrane vesiculation, and activates secretion. We hypothesized that complement might also alter interactions of the endothelial surface with lipoproteins, particularly high density lipoprotein (HDL), which is reported to inhibit C5b-9-induced hemolysis. We now demonstrate that exposure to C5b-9 increases (by 2- to 50-fold) specific binding of HDL and its apolipoproteins (apo) A-I and A-II to endothelial cells. Binding to cells exposed to antibody, C5b67, and C5b-8 was virtually unchanged. Enhanced binding was also dependent on the number of C5b-9 complexes deposited on the cells. Other agonists that activate endothelial secretion did not augment binding. Calcium was required for full exposure of new binding sites by C5b-9. The C5b-9-induced increase in binding was independent of the increase observed after cholesterol loading. In addition, apo A-I and A-II appear to compete for the same binding sites on untreated and C5b-9-treated cells. In contrast to the data reported for red cells, we were unable to detect significant inhibition of C5b-9-mediated endothelial membrane permeabilization by HDL (up to 1 mg/ml) or by apo A-I (up to 100 micrograms/ml). These data demonstrate that the C5b-9 proteins enhance endothelial binding of HDL and its apoproteins, suggesting that intravascular complement activation may alter cholesterol homeostasis in the vessel wall. PMID- 1752945 TI - Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation. AB - Parathyroid hormone-related protein (PTHrP), which is responsible for producing hypercalcemia in patients with humoral hypercalcemia of malignancy, has recently been identified in several normal tissues. Because PTHrP, like parathyroid hormone (PTH), is known to exhibit vasodilatory properties, we investigated the expression and regulation of PTHrP mRNA in cultured rat aortic smooth muscle cells (SMC). We report here that PTHrP mRNA is expressed in SMC and is markedly induced by serum in a time- and concentration-dependent fashion. Addition of 10% fetal calf serum to serum-deprived, confluent cells, resulted in a marked induction of PTHrP mRNA by 2 h with a peak at 4-6 h. PTHrP was detected in SMC by immunocytochemistry and radioimmunoassay of conditioned medium, and was shown to be up-regulated within 24 h after the addition of serum. The serum induction of PTHrP mRNA was blocked by actinomycin D and by cycloheximide indicating the need for protein synthesis to evoke the serum effect on PTHrP gene transcription. In addition, treatment with dexamethasone, which has been previously shown to reduce the constitutive expression of PTHrP in human cancer cells, also blunted the serum induction of PTHrP mRNA in SMC. Treatment of quiescent cells with the serum mitogens platelet-derived growth factor or insulin-like growth factor-I had no effect on PTHrP, whereas the vasoactive peptides endothelin, norepinephrine and thrombin stimulated PTHrP expression. Exogenous addition of recombinant PTHrP-(1 141) had no significant effect on SMC DNA synthesis as measured by [3H]thymidine incorporation. In summary, the abundance of PTHrP mRNA and the characteristics of its regulation in SMC suggest a major role for PTHrP as a local modulator in vascular smooth muscle. PMID- 1752946 TI - Xanthine oxidase inhibits growth of Plasmodium falciparum in human erythrocytes in vitro. AB - Malaria parasites, unable to synthesize purine de novo, use host-derived hypoxanthine preferentially as purine source. In a previous study (1990. J. Biol. Chem. 265:6562-6568), we noted that xanthine oxidase rapidly and completely depleted hypoxanthine in human erythrocytes, not by crossing the erythrocyte membrane, but rather by creating a concentration gradient which facilitated hypoxanthine efflux. We therefore investigated the ability of xanthine oxidase to inhibit growth of FCR-3, a chloroquine-resistant strain of Plasmodium falciparum in human erythrocytes in vitro. Parasites were cultured in human group O+ erythrocytes in medium supplemented, as required, with xanthine oxidase or chloroquine. Parasite viability was assessed by uptake of radiolabeled glycine and adenosine triphosphate-derived purine into protein and nucleic acid, respectively, by nucleic acid accumulation, by L-lactate production, and by microscopic appearance. On average, a 90% inhibition of growth was observed after 72 h of incubation in 20 mU/ml xanthine oxidase. Inhibition was notably greater than that exerted by 10(-7) M chloroquine (less than 10%) over a comparable period. The IC50 for xanthine oxidase was estimated at 0.2 mU/ml, compared to 1.5 x 10(-7) M for chloroquine. Inhibition was completely reversed by excess hypoxanthine, but was unaffected by oxygen radical scavengers, including superoxide dismutase and catalase. The data confirms that a supply of host derived hypoxanthine is critical for nucleic acid synthesis in P. falciparum, and that depletion of erythrocyte hypoxanthine pools of chloroquine-resistant malaria infection in humans. of chloroquine-resistant malaria infection in humans. PMID- 1752947 TI - Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency. AB - The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes for distinct point mutations dispersed throughout the LPL gene. Patient 1 has a G-to-A transition at the first nucleotide of intron 2, which abolishes normal splicing. Patient 2 has a nonsense mutation in exon 3 (Tyr61----Stop) and patient 3 in exon 8 (Trp382----Stop). The latter mutation emphasizes the importance of the carboxy-terminal portion of the enzyme in the expression of LPL activity. Missense mutations were identified in patient 4 (Asp204----Glu) and patient 5 (Arg243----His) in the strictly conserved amino acids. Expression study of both mutant genes in COS-1 cells produced inactive enzymes, establishing the functional significance of the two mis-sense mutations. In these patients, postheparin plasma LPL mass was either virtually absent (patients 1 and 2) or significantly decreased (patients 3-5). To detect these mutations more easily, we developed a rapid diagnostic test for each mutation. We also determined the DNA haplotypes for patients and confirmed the occurrence of multiple mutations on the chromosomes with an identical haplotype. These results demonstrate that familial LPL deficiency is a heterogeneous genetic disease caused by a wide variety of gene mutations. PMID- 1752948 TI - Induction of omega-oxidation of monocarboxylic acids in rats by acetylsalicylic acid. AB - The accumulation of dicarboxylic acids, particularly long chain, is a prominent feature of Reye's syndrome and diseases of peroxisomal metabolism. We assessed the omega-oxidation of a spectrum of fatty acids in rats and asked whether pretreatment of rats with aspirin, which is known to predispose children to Reye's syndrome, would affect omega-oxidation of long chain fatty acids. We found that aspirin increased liver free fatty acids and increased the capacity for omega-oxidation three- to sevenfold. Omega-oxidation of long chain substrate was stimulated to a greater degree than medium chain substrate and was apparent within one day of treatment, at serum aspirin concentrations below the therapeutic range in humans. The apparent Km for lauric acid was 0.9 microM and 12 microM for palmitate. We also found a difference in the storage stability of activity toward medium and long chain substrate. Saturating concentrations of palmitate had no effect on the formation of dodecanedioic acid, whereas laurate decreased but never eliminated the omega-oxidation of palmitate. 97% of the total laurate omega-oxidative activity recovered was found in the microsomes, but 32% of palmitate omega-oxidative activity was present in the cytosol. These results demonstrate that aspirin is a potent stimulator of omega-oxidation and suggest that there may be multiple enzymes for omega-oxidation with overlapping substrate specificity. PMID- 1752949 TI - Photosensitized killing of cultured fibroblasts from patients with peroxisomal disorders due to pyrene fatty acid-mediated ultraviolet damage. AB - The influence of pyrene-fatty acids on the resistance of cells to ultraviolet (UV) radiation was investigated in cultured fibroblasts from patients with five types of peroxisomal disorders. All showed reduced survival compared to control. The effect varied with the biochemical defect involved and the chain length of the pyrene fatty acid. Reduced survival was observed in cells deficient in plasmalogens (rhizomelic chondrodysplasia punctata) and in cells deficient in peroxisomal fatty acid oxidation (bifunctional enzyme deficiency), which accumulated pyrene-fatty acids. X-linked adrenoleukodystrophy fibroblasts accumulated pyrene-fatty acids and showed increased UV sensitivity only when exposed to longer-chain pyrene fatty acids. UV radiation resistance was lowest in cells with combined impairment of plasmalogen synthesis and fatty acid oxidation (Zellweger syndrome, neonatal adrenoleukodystrophy), suggesting that UV sensitivity correlates inversely with the ratio of plasmalogens to radical producing substances. Fibroblasts deficient in plasmalogens gained normal UV resistance when their plasmalogen levels were normalized by hexadecylglycerol. UV resistance increased when Zellweger cells were fused with X-linked adrenoleukodystrophy cells, and also when Zellweger cells belonging to different complementation groups were fused. The results provide leads to the pathogenesis of the multiple malformations associated with peroxisomal disorders and a method for the selection of cells in which the metabolic defect has been corrected. PMID- 1752950 TI - Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo. AB - Hydrogen peroxide (H2O2) contributes to renal cellular injury. alpha-Keto acids nonenzymatically reduce H2O2 to water while undergoing decarboxylation at the 1 carbon (1-C) position. We examined, in vitro and in vivo, the protective role of sodium pyruvate in H2O2-induced renal injury. Pyruvate effectively scavenged H2O2 in vitro, and suppressed H2O2-induced renal lipid peroxidation. Injury to LLC-PK1 cells induced by hydrogen peroxide was attenuated by pyruvate to an extent comparable to that seen with catalase. Studies utilizing [1-14C]pyruvate further demonstrated 1-C decarboxylation concurrent with cytoprotection by pyruvate from H2O2-induced injury. Pyruvate was also protective in vivo. Infusion of pyruvate before and during the intrarenal infusion of H2O2 attenuated H2O2-induced proteinuria. Systemic administration of pyruvate was also protective in the glycerol model of acute renal failure, a model also characterized by increased generation of H2O2. These findings indicate that pyruvate, a ubiquitous alpha keto acid, scavenges H2O2 and protects renal tissue in vitro and in vivo from H2O2-mediated injury. These data suggest a potential therapeutic role for pyruvate in diseases in which increased generation of H2O2 is incriminated in renal damage. PMID- 1752951 TI - Cholesterol enrichment increases basal and agonist-stimulated calcium influx in rat vascular smooth muscle cells. AB - The effect of cholesterol enrichment on vascular smooth muscle cell (VSMC) calcium homeostasis was studied by evaluating calcium uptake, efflux, and intracellular content in cultured VSMC derived from the rat pulmonary artery. Incubation of VSMC with liposomes consisting of free cholesterol (FC) and phospholipid (2:1 molar ratio, 1 mg FC/ml medium) for 24 h resulted in a 69 +/- 19% increase (P less than 0.01; n = 10) in FC which was associated with a 73 +/- 11% increase (P less than 0.005; n = 10) in intracellular calcium content as assessed by isotopic equilibrium with 45Ca2+ and a 65 +/- 11% increase (P less than 0.024; n = 3) as assessed by atomic absorption spectroscopy. Cholesterol enrichment caused a marked increase in the unidirectional calcium uptake rate from 0.026 +/- 0.03 to 0.158 +/- 0.022 nmol calcium/s per mg protein (P less than 0.01; n = 3), but had no effect on calcium efflux. Nifedipine (1 microM) reduced (P less than 0.05; n = 6) the effect of cholesterol enrichment on unidirectional calcium uptake by 78 +/- 16%; and verapamil (10 microM), diltiazem (1 microM), and nifedipine (1 microM) each significantly inhibited the effect of cholesterol enrichment on intracellular calcium accumulation. Exposure of cholesterol enriched VSMC to cholesterol-poor liposomes for 24 h returned both FC and calcium contents to control levels. Serum- and serotonin-stimulated calcium uptakes were potentiated 3.7- and 1.7-fold, respectively, in cholesterol-enriched VSMC, whereas endothelin, vasopressin, and thrombin-stimulated calcium uptakes were not affected. We conclude that VSMC FC content plays a role in regulating cellular calcium homeostasis, both under basal conditions and in response to selected agonists. PMID- 1752952 TI - A 3' splice site mutation in the thyroglobulin gene responsible for congenital goiter with hypothyroidism. AB - A case of congenital goiter with defective thyroglobulin synthesis has been studied in molecular terms. The patient is the fifth of a kindred of six, three of which have a goiter. The parents are first cousins. Segregation of thyroglobulin alleles in the family was studied by Southern blotting with a probe revealing a diallelic restriction fragment length polymorphism (RFLP). The results demonstrated that the three affected siblings were homozygous for the RFLP. Northern blotting analysis of the goiter RNA with a thyroglobulin probe suggested that thyroglobulin mRNA size was slightly reduced. Polymerase chain reaction amplification of the 8.5-kb thyroglobulin mRNA as overlapping cDNA fragments demonstrated that a 200-bp segment was missing from the 5' region of the goiter mRNA. Subcloning and sequencing of the cDNA fragments, and of the patient genomic DNA amplified from this region, revealed that exon 4 is missing from the major thyroglobulin transcript in the goiter, and that this aberrant splicing is due to a C to G transversion at position minus 3 in the acceptor splice site of intron 3. The presence in exon 4 of a putative donor tyrosine residue (Tyrosine nr 130) involved in thyroid hormone formation provides a coherent explanation to the hypothyroid status of the patient. PMID- 1752953 TI - Endogenous adenosine is an autacoid feedback inhibitor of chloride transport in the shark rectal gland. AB - The present studies define the physiologic role of endogenous adenosine in the perfused shark rectal gland, a model epithelia for hormone-stimulated chloride transport. Chloride ion secretion, and venous adenosine and inosine concentrations increased in parallel in response to hormone stimulation. From a basal rate of 157 +/- 26 mu eq/h per g, chloride secretion increased to 836 +/- 96 and 2170 +/- 358 with 1 and 10 microM forskolin, venous adenosine increased from 5.0 +/- 1 to 126 +/- 29 and 896 +/- 181 nM, and inosine increased from 30 +/ 9 to 349 +/- 77 and 1719 +/- 454 nM (all P less than 0.01). Nitrobenzylthioinosine (NBTI), a nucleoside transport inhibitor, completely blocked the release of adenosine and inosine. Inhibition of chloride transport with bumetanide, an inhibitor of the Na+/K+/2Cl- cotransporter, or ouabain, an inhibitor of Na+/K+ ATPase activity, reduced venous adenosine and inosine to basal values. When the interaction of endogenous adenosine with extracellular receptors was prevented by adenosine deaminase, NBTI, or 8-phenyltheophylline, the chloride transport response to secretagogues increased by 1.7-2.3-fold. These studies demonstrate that endogenous adenosine is released in response to hormone stimulated cellular work and acts at A1 adenosine receptors as a feedback inhibitor of chloride transport. PMID- 1752954 TI - Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo. AB - The concept of using thyroid-stimulating hormone (TSH) receptor antagonists in the management of Graves' disease is intriguing. Therefore, we investigated a TSH receptor antagonist derived from human chorionic gonadotropin (hCG) with respect to TSH receptor binding, adenylate cyclase activity, thyroid hormone release, and HLA class II antigen expression in vitro and in an in vivo model. A variant of hCG, asialoagalacto-hCG, like asialo-hCG and unlike hCG itself, inhibited both 125I-bTSH binding and cAMP response to bTSH in human thyroid membranes. However, like intact or deglycosylated hCG and unlike asialo-hCG, asialoagalacto-hCG displayed a limited affinity for hepatic asialoglycoprotein receptors, a likely marker for its in vivo turnover rate. It proved capable of inhibiting bTSH stimulated thyroid hormone release in human thyroid slices as well as in the nude mouse bearing human thyroid transplants. It also prevented bTSH induced hypertrophy of transplanted thyrocytes. Further, HLA-DR expression induced by bTSH in the presence of gamma-interferon on human thyrocytes was inhibited. In conclusion, we present evidence that asialogalacto-hCG antagonizes bTSH actions on thyroid function and HLA-DR expression in human thyroid in vitro and, more importantly, in an in vivo model. Hence, the hCG variant described here or similar agents should warrant further exploration in the study and treatment of Graves' disease. PMID- 1752955 TI - Effects of alpha-thalassemia and sickle polymerization tendency on the urine concentrating defect of individuals with sickle cell trait. AB - A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal alpha globin genotype (alpha alpha/alpha alpha), and those who were either heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha thalassemia, because alpha-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the alpha alpha/alpha alpha genotype than in the -alpha/alpha alpha or -alpha/-alpha genotypes (P less than 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/ alpha genotype than with the -alpha/alpha alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (P less than 0.05); patients with the -alpha/alpha alpha genotype had greater concentrating ability than individuals with a normal alpha-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = 0.654; P less than 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the alpha-globin genotype. PMID- 1752956 TI - Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. AB - Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant pellet was analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, and minimum surface tension (STmin). PL was decreased in both AR and A (3.48 +/- 0.61 and 2.47 +/- 0.40 mumol/ml, respectively) compared to N (7.99 +/- 0.60 mumol/ml). Phosphatidylcholine was decreased in A (62.64 +/- 2.20% PL) compared to N (76.27 +/- 2.05% PL). Phosphatidylglycerol was 11.58 +/- 1.21% PL in N and was decreased to 6.48 +/- 1.43% PL in A. SP-A was 123.64 +/- 20.66 micrograms/ml in N and was decreased to 49.28 +/- 21.68 micrograms/ml in AR and to 29.88 +/- 8.49 micrograms/ml in A. SP-B was 1.28 +/- 0.33 micrograms/ml in N and was decreased to 0.57 +/- 0.24 micrograms/ml in A. STmin was increased in AR (15.1 +/- 2.53 dyn/cm) and A (29.04 +/- 2.05 dyn/cm) compared to N (7.44 +/- 1.61 dyn/cm). These data demonstrate that the chemical composition and functional activity of surfactant is altered in ARDS. Several of these alterations also occur in AR, suggesting that these abnormalities occur early in the disease process. PMID- 1752957 TI - Eosinophil hematopoietins antagonize the programmed cell death of eosinophils. Cytokine and glucocorticoid effects on eosinophils maintained by endothelial cell conditioned medium. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with IL-1 alpha (5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM (P less than 0.05). Dexamethasone (100 nM) decreased the constitutive GM-CSF elaboration by 49% (P less than 0.001) but did not diminish production by IL-1 alpha-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-1 alpha-stimulated endothelial cell-conditioned medium (P less than 0.05), which suggested viability antagonism by glucocorticoids. After 24 h of culture, eosinophil viability for replicate cells in enriched medium alone or with 1 pM GM-CSF decreased from means of 43 and 75% to means of 21 and 54%, respectively, when dexamethasone was included (P less than 0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonuclease-specific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathobiologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentrations that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of select eosinophilic disorders to glucocorticoids. PMID- 1752958 TI - Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys. AB - The effect of estrogen and progesterone replacement therapy on the initiating events in atherogenesis was studied in surgically postmenopausal cynomolgus monkeys. Monkeys were ovariectomized and divided randomly into two groups, one receiving 17 beta-estradiol and cyclic progesterone treatment (n = 9) and ovariectomized controls receiving no hormone replacement therapy (n = 8). The monkeys were fed a moderately atherogenic diet for 18 wk to accelerate the early pathogenic processes but not to be of sufficient duration to produce grossly visible atherosclerotic lesions. Sex hormone replacement therapy decreased the accumulation of LDL and products of LDL degradation in the coronary arteries by greater than 70% while having no significant effect on plasma lipid, lipoprotein, or apoprotein concentrations. Arterial intimal lesions were small with no difference between groups. The reduction in arterial LDL metabolism occurred very early in the pathogenesis of atherosclerosis and was independent of indices of endothelial cell injury, such as enhanced endothelial cell turnover or leukocyte adhesion to the endothelium. Results of this study suggest that one mechanism by which sex hormone treatment inhibits the initiation of atherosclerosis is a direct effect at the level of the arterial wall by suppressing the uptake and/or degradation of LDL. PMID- 1752959 TI - A single myocardial stretch or decreased systolic fiber shortening stimulates the expression of heat shock protein 70 in the isolated, erythrocyte-perfused rabbit heart. AB - The regulation of heat shock protein 70 (HSP 70) expression was examined in the isolated, red blood cell-perfused rabbit heart by Northern and Western blot analysis. In the isovolumic (balloon in left ventricle), isolated perfused heart, HSP 70 mRNA was increased threefold after 30 min and sevenfold at 2 and 4 h compared to normal, nonperfused hearts. To further elucidate the etiology of the increase in HSP 70 mRNA, the effects of decreased systolic shortening (isovolumic heart) and of a single ventricular stretch were examined. Perfusion without the application of a stretch or the presence of a balloon resulted in no increase in HSP 70 mRNA; while a single stretch resulted in a threefold increase in HSP 70 mRNA. These changes were accompanied by an increase in HSP 70 protein by Western blot analysis. To elucidate the signalling mechanism mediating the increase in HSP 70, hearts were perfused with H7, a protein kinase C inhibitor. H7 did not prevent the induction of HSP 70. These results indicate that initiation of expression of myocardial HSP 70 can be stimulated by a single myocardial stretch or by prevention of systolic shortening. These mechanisms may contribute to the rapid expression of HSP 70 after coronary occlusion when dyskinesis, reduced systolic shortening, and increased diastolic segment length all occur. PMID- 1752960 TI - On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin. AB - Tumor necrosis factor (TNF), a protein released by activated macrophages, is a central mediator of the host response to infection and inflammation. The TNF binding protein I (TNF-BP-I) is a soluble fragment of the p60 transmembrane TNF receptor and an antagonist to TNF. The level of serum TNF-BP-I was found to be increased in patients with renal insufficiency as a result of a decrease in the glomerular filtration rate. During hemodialysis of patients with renal failure there was a rapid but transient increase in serum TNF-BP-I. This increase was found to be caused by heparin given before dialysis and a similar dose-dependent response to heparin was observed also in healthy individuals. The finding of a repeated release of TNF-BP-I into the circulation with intermittent injections of heparin indicates that TNF-BP-I is present both in a storage pool and in a circulating pool. The mechanism for the heparin-mediated release of TNF-BP-I was not explained; TNF-BP did not show affinity for heparin. On the other hand, TNF was found to have affinity for heparin and it could also be dissociated from heparin by TNF-BP-I. It is suggested that heparin-like molecules of the extracellular matrix can retain TNF in physical proximity with target cells and restrict the actions of TNF and protect against systemic harmful manifestations. PMID- 1752961 TI - Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. AB - Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2 fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1 fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration. PMID- 1752962 TI - Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism. AB - To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced. PMID- 1752963 TI - Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. AB - The effects of FFA on hepatic insulin clearance were studied in the in situ perfused rat liver. Clearance decreased with increasing body weight (age) of the rats. When FFA were added to the perfusate a 40% reduction of hepatic removal of insulin was found over the normal, physiological range (less than 1,000 mumol/liter), less pronounced in heavier rats. When perfusion was started with high concentrations of FFA, inhibition was rapidly reversible, a phenomenon again blunted in heavier rats. In contrast to FFA, different glucose concentrations in the perfusate did not affect the hepatic insulin uptake in the presence of FFA within physiological concentrations. Thus, hepatic clearance of insulin is proportional to rat weight (age) and portal FFA concentrations. Other studies have recently shown that fatty acids inhibit insulin binding, degradation, and function in isolated rat hepatocytes, and that hepatic clearance is inversely dependent on hepatic triglyceride concentrations, both inhibitions reversible by prevention of fatty acid oxidation. It is suggested that the diminished hepatic clearance of insulin in heavier (older) rats is at least partly due to their relative obesity and increased hepatic triglyceride contents. This effect as well as that of portal FFA is probably mediated via fatty acid oxidation in the liver. This mechanism may have implications for the regulation of hepatic metabolism, and peripheral insulin concentrations. PMID- 1752964 TI - Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. AB - Plasma net cholesteryl ester (CE) transfer and optimum cholesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (n = 11) and normolipidemic (n = 15) individuals. The hypertriglyceridemic group demonstrated threefold greater net CE transfer leading to enhanced accumulation of CE in VLDL. This increased net transfer was not accompanied by a change in CETP activity. In normolipidemia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P less than 0.001). In contrast, net CE transfer in hypertriglyceridemia, but not in normolipidemia, correlated with CETP activity (r = 0.73, P less than 0.01). Correction of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P less than 0.005) while suppressing the correlation with CETP activity. That net CE transfer depends on VLDL concentration was confirmed by an increase of net CE transfer in normolipidemic plasma supplemented with purified VLDL. Supplementation of purified CETP to normolipidemic plasma did not stimulate net CE transfer. In contrast, net CE transfer was enhanced by addition of CETP to both plasma supplemented with VLDL and hypertriglyceridemic plasma. Thus, in normal subjects, VLDL concentration determines the rate of net CE transfer. CETP becomes rate limiting as VLDL concentration increases, i.e., in hypertriglyceridemia. PMID- 1752965 TI - Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance. AB - In patients with congestive heart failure (CHF), the poor relationship between systemic exercise performance and cardiac function, together with morphologic and metabolic abnormalities in skeletal muscle, raises the possibility that skeletal muscle function may be impaired and limit systemic exercise performance. We assessed strength and endurance of the knee extensors during static and dynamic exercise in 16 patients with Class I-IV CHF and eight age-matched sedentary controls and related these measurements to systemic exercise performance. To assess skeletal muscle function independent of peripheral blood flow, endurance was repeated under ischemic conditions. Strength was not significantly different in the two groups. Dynamic endurance, quantified as the decline in peak torque during 15 successive isokinetic knee extensions, was significantly reduced in the patients compared to controls during aerobic (peak torque 65 vs. 86% of initial for exercise at 90 deg/s and 60 vs. 85% for exercise at 180 deg/s; P less than 0.002 for both), and during ischemic exercise (56 vs. 76% of initial torque; P less than 0.01). Static endurance, defined as the time required for force during a sustained maximal voluntary contraction to decline to 60% of maximal, was reduced in the patients compared to controls (40 +/- 14 vs. 77 +/- 29 s; P less than 0.02). There were highly significant relationships between systemic exercise performance and skeletal muscle endurance at 90 and 180 deg/s in the patients with CHF (r = 0.90 and 0.66, respectively). These findings indicate that skeletal muscle endurance is impaired in patients with CHF, that this abnormality is in part independent of limb blood flow, and that these changes may be important determinants of systemic exercise performance. PMID- 1752966 TI - Water deprivation stimulates transforming growth factor-beta 2 accumulation in the juxtaglomerular apparatus of mouse kidney. AB - Transforming growth factor-beta (TGF-beta) modulates the growth and differentiation of many cells and often functions in an autocrine or paracrine fashion. The myoepithelial cells of the renal juxtaglomerular apparatus (JGA) synthesize and secrete renin. Under conditions which chronically stimulate renin production, the JGA undergoes hypertrophy and hyperplasia. The molecular factors responsible for these changes in the JGA have not been identified. In the present study, plasma renin activity was stimulated in the mouse by water deprivation. Using immunoperoxidase staining with specific antibodies against TGF-beta 1, beta 2, and beta 3, we found increased TGF-beta 2 accumulation in the JGA and interlobular arteries. Immunostaining with renin antiserum demonstrated colocalization of TGF-beta 2 and renin. TGF-beta 1 and beta 3 expression was not different between control and water-deprived mice. Our results suggest that in the setting of water deprivation, TGF-beta 2 is localized in a manner which would allow it to act either as a growth factor for or as a phenotypic modulator of the JGA and renal arterioles. PMID- 1752967 TI - Expression of the hepatocellular chloride-dependent sulfobromophthalein uptake system in Xenopus laevis oocytes. AB - The expression of the basolateral chloride-activated organic anion uptake system of rat hepatocytes has been studied in Xenopus laevis oocytes. Injection of oocytes with rat liver poly(A)+RNA resulted in the functional expression of chloride-dependent sulfobromophthalein (BSP) uptake within 3-5 d. This expressed chloride-dependent BSP uptake system exhibited saturation kinetics (apparent Km approximately 6.2 microM) and efficiently extracted BSP from its binding sites on BSA. Furthermore, the chloride-activated portion of BSP uptake was inhibited by bilirubin (10 microM; inhibition 53%), 4,4'-diisothiocyano-2,2-disulfonic acid stilbene (DIDS, 100 microM; 80%), taurocholate (100 microM; 80%), and cholate (200 microM; 95%). In contrast to results with total rat liver mRNA, injection of mRNA derived from the Na+/bile acid cotransporter cDNA (Hagenbuch, B., B. Stieger, M. Foguet, H. Lubbert, and P. J. Meier. 1991. Proc. Natl. Acad. Sci. USA. In press.) had no effect on BSP uptake into oocytes. Size fractionation of total rat liver mRNA revealed that a 2.0- to 3.5-kb size-class mRNA was sufficient to express the hepatic chloride-dependent BSP uptake system. These data indicate that "expression cloning" in oocytes represents a promising approach to ultimately clone the cDNA coding for the hepatocyte high affinity, chloride-dependent organic anion uptake system. Furthermore, the results confirm that the Na+/bile acid cotransport system does not mediate BSP uptake. PMID- 1752968 TI - Restricted opening of the mouth with an extra-articular cause in children. AB - Restricted opening of the mouth with an extra-articular cause (ROMEC) can have very different aetiologies. A series of 6 children, who have been operated on under 4 different diagnoses, are presented. Excluded are common problems such as recent trauma and posttraumatic scarring, craniomandibular dysfunction or elongated coronoid process, and also tumours. Problems of establishing the diagnosis, surgical treatment, postoperative physiotherapy and timing are discussed. It is shown that none of the cases is a perfect result, some outcomes are even very disappointing. It is therefore concluded that absolute trismus should be treated independently of age. The result expected will be mediocre. For final correction it is suggested that the operator should wait preferably until the second growth spurt has passed. The same goes for children presenting primarily with a mouth opening greater than 20 mm. PMID- 1752969 TI - Evaluation of masticatory function following orthognathic surgical correction of mandibular prognathism. AB - Masticatory function was examined in 17 patients with mandibular prognathism before and after bilateral sagittal splitting osteotomy of the mandibular rami. Masticatory efficiency was measured by means of a spectrophotometer, using adenosine triphosphate (ATP) granules, the biting force and occlusal contact area. Masticatory functions showed a tendency to gradual improvement postoperatively. Concerning masticatory efficiency, mean values of absorbance of ATP granules in patients with mandibular prognathism were inferior to those of subjects who possess a normal occlusion, even 12 months after operation. PMID- 1752970 TI - Soft tissue changes after advancement genioplasty performed as pedicled or free transplants. AB - The influence of soft tissue attachment in augmentation genioplasty on postoperative soft tissue changes was studied in 25 patients. The soft tissue was completely detached from the advanced genial segment in 14 patients and lingual soft tissue was maintained in 11 patients. The patients were followed for a minimum of 1 year after operation and the soft tissue and bone changes were analysed by measuring linear distances and areas on lateral cephalograms. The result indicated that the soft tissue changes after surgery were significantly different between the two types of graft. In the free grafts there was found to be an increased risk of creating a larger interlabial gap and exposure of the labial surface of mandibular incisors. The higher correlations between hard and soft tissue changes in the pedicled grafts indicated that the predictability is better with this operative technique. PMID- 1752971 TI - The Egyedi flap in secondary cleft lip repair. AB - The Egyedi flap is a reliable technique for secondary lip repair in cases with tilting mismatches at the vermilion cutaneous border and asymmetrical vermilion excess in a lip of normal volume and sufficient length. PMID- 1752972 TI - The status of the resection margin as a prognostic factor in the treatment of head and neck carcinoma. AB - The value of the status of the resection margin as a prognostic factor after surgical treatment was investigated in 80 patients with squamous cell carcinoma of the oral cavity, oropharynx and laryngohypopharynx. The relation of locoregional recurrence with the presence or absence of tumour at the surgical margin was analysed together with other indications for postoperative radiotherapy. Locoregional recurrence was observed in 20% and was correlated with tumour thickness over 5 mm, spidery growth and tumour-positive margins. Tumour positive margin as a single indication for postoperative irradiation was not related to an increased recurrence rate. When however occurring together with other indications for postoperative irradiation, the recurrence rate was higher than in the patient group with the same number of indications for postoperative radiotherapy but without tumour at the surgical margins. PMID- 1752973 TI - Chondroblastoma of the temporal bone. Case report. AB - A case of chondroblastoma of the temporal bone in a 53-year-old male patient is presented. The diagnostic and therapeutic processes are discussed. PMID- 1752974 TI - Unusual ameloblastoma with extensive stromal desmoplasia. AB - A clinicopathological study of 5 cases of unusual ameloblastoma was performed. Three cases were characterized by marked stromal desmoplasia. The lesions occurred in the tooth-bearing areas of the anterior or premolar regions of the jaw. They were relatively small and showed a honeycomb appearance radiographically. Histologically, the islands of tumour cells were small and discrete in the widely extended desmoplastic stroma. They lacked obvious ameloblastic polarity in many parts. The other 2 cases were hybrid lesions of desmoplastic and conventional types. The former appeared in the alveolar part and the latter in the lower part of the mandible. It was concluded that the desmoplastic variant of ameloblastoma could be categorized as a new distinct type histologically, clinically and radiographically. PMID- 1752975 TI - Current concerns in haematology. 3: Blood count calibration. PMID- 1752976 TI - Guidelines on testing for the lupus anticoagulant. Lupus Anticoagulant Working Party on behalf of the BCSH Haemostasis and Thrombosis Task Force. PMID- 1752977 TI - ACP Broadsheet 130: November 1991. Gross examination of bladder specimens. PMID- 1752978 TI - Endocervical carcinoma and precursor lesions: c-myc expression and the demonstration of field changes. AB - The monoclonal antibody Myc 1-6E10 was used in an immunocytochemical technique to examine the expression of the c-myc oncogene in normal endocervices and those with glandular intraepithelial neoplasia and invasive malignancy. Eleven of 14 normal endocervical biopsy specimens did not express the gene, while three showed nuclear, or light basal cytoplasmic localisation of the gene product, or both. All but one of 14 cases of low and high grade glandular intraepithelial neoplasia, and all 17 cases of invasive adenocarcinoma, showed a pan-cellular pattern of immunostaining. Of considerable additional interest was the demonstration of field changes in morphologically normal glandular epithelium in those biopsy specimens with concurrent cervical glandular intraepithelial neoplasia or adenocarcinoma. This was manifest as increased concentrations of myc proteins compared with normal tissues. These results further support the role of the c-myc gene in oncogenesis, and in the light of field changes, suggest possible difficulties in the clinical management of this group of patients. PMID- 1752979 TI - Feasibility of in situ hybridisation with chromosome specific DNA probes on paraffin wax embedded tissue. AB - The feasibility was studied of in situ hybridisation using chromosome specific DNA probes on paraffin wax embedded normal and malignant tissues from different organs. Both isolated nuclei and 5 microns sections were used in in situ hybridisation experiments with biotinylated repetitive DNA probes specific for the centromeric regions of chromosomes 1 and 17. The hybridisation results were visualised with peroxidase-diaminobenzidine. The optimal pretreatments with sodium thiocyanate and pepsin were experimentally defined for the different tissues. Although interphase cytogenetics on paraffin wax embedded tissue is possible, the results indicate that it has its limitations, compared with investigations on fresh tumour tissue. PMID- 1752980 TI - Rapid detection of hepatitis B virus DNA in liver tissue by in situ hybridisation and its combination with immunohistochemistry for simultaneous detection of HBV antigens. AB - A rapid technique using a non-radioactive receptor molecule (digoxigenin) for intrahepatic hepatitis B virus (HBV) DNA detection using in situ hybridisation was developed. It can be adapted for use in combination with standard immunohistochemistry for simultaneous detection of both HBV DNA and HBV antigens. The total time required for dual detection of HBV antigens and HBV DNA starting from paraffin wax liver sections was two working days. A good signal to background ratio for the detection of HBV DNA was always obtained using this labelling. This technique is cheap, safe, and relatively simple which makes it an ideal tool for the detection of intrahepatic HBV DNA for both routine diagnostic purposes and in research. PMID- 1752981 TI - Central pontine myelinolysis in liver transplantation. AB - Five cases of central pontine myelinolysis (CPM) were detected by neuropathological examination in a series of 50 patients coming to necropsy after liver transplantation. One patient also had extrapontine myelinolysis. In no case was the diagnosis made during life. Only two patients showed rapid rises in serum sodium concentrations. The incidence of hyponatraemia, before and after transplantation, and rapid rises in serum sodium in patients with CPM was significantly greater than in the 45 patients showing no neuropathological evidence of CPM. It is concluded that there is a high incidence of CPM after liver transplantation, that clinical diagnosis is difficult, and that there is no simple direct correlation between rapid serum sodium changes and the development of this condition. Avoidance of major electrolyte fluctuations at the time of liver transplantation is recommended but it must be emphasised that CPM may occur without any rapid rise in serum sodium concentration. PMID- 1752982 TI - Early delayed hypersensitivity responses in tuberculin skin tests after heavy occupational exposure to tuberculosis. AB - The early (six hours) reaction to tuberculin skin testing was studied in 33 Indonesian hospital workers with frequent occupational exposure to M tuberculosis and compared with responses maximal at the usual time (48 hours) in factory workers, from the same locality but with only occasional occupational exposure, to determine the nature of the early reaction. The early reaction had the same general histopathological appearance as that seen in the conventional (48 hour) reaction, and both had an infiltrate consisting largely of T lymphocytes and macrophages. The cell densities were lower in the six hour reactions, but the relative concentration of macrophages was greater in the earlier response. These histometric measurements suggested that the six hour reaction was an accelerated delayed hypersensitivity reaction. Moreover, the absence of a specific IgE response or of particulate masses of Ig or complement, made it unlikely an anaphylactoid or Arthus-type reaction could have been responsible. It is concluded that those with frequent occupational exposure to M tuberculosis have larger numbers of circulating T cells reactive with mycobacterial antigens, so that the development of the skin test response to tuberculin is less dependent on "by-stander" cell infiltration to mediate the delayed hypersensitivity reaction than the reactions in those with less intense and less frequent natural exposure. The skin test response maximal at six hours is probably a hyperimmune reaction to an antigen recognised by T cells. PMID- 1752983 TI - Removal of inhibitor(s) of the polymerase chain reaction from formalin fixed, paraffin wax embedded tissues. AB - A problem associated with use of the polymerase chain reaction to amplify specific DNA fragments from formalin fixed, paraffin wax embedded tissues is the not infrequent failure of amplification. One possible reason for this could be the presence of inhibitor(s), which interfere with the activity of the reaction. It has been shown that such inhibitor(s) exist when amplifying the human beta globin gene (which exists in human genomic DNA as a single copy gene) from routine clinical samples. A variety of methods to remove such inhibitor(s) were investigated. The results indicate that inhibitor(s) are removed by proteinase K digestion, followed by purification with phenol/chloroform, and centrifugation through a Centricon-30 membrane (30,000 molecular weight cut off). Other factors, including the length and concentration of the DNA sequence to be amplified, can also affect amplification. PMID- 1752984 TI - Prospective study of quantitative aspects of audit in a large general histopathology laboratory. AB - A non-computerised method of accurate prospective analysis of the quantitative aspects of the work of a general histopathology laboratory was devised. The method entails monitoring the progress of all biopsy and cytology specimens through the laboratory during selected monthly periods of study. The data collected include details of specimen type, block/section/stain details for each specimen, and information about the timed progress through technical, medical, and secretarial stages of specimen/report handling. The results give a detailed breakdown of the biopsy and cytology workload of this department. They give information about the rate of passage of specimens through the system and identify reasons for delay in the reporting of some cases. The method is easy to operate and will allow for the analysis of specific effects--for example, staff changes--on the efficiency of the department. The data will also provide some of the information required for the costing of histopathology laboratory services, and the type of information obtained will probably become a necessary requirement for laboratory accreditation. PMID- 1752985 TI - Western blot analysis of immune response to Legionella bozemanii antigens. AB - The immune response to individual major antigens of Legionella bozemanii was studied in 67 sera from 26 inpatients with febrile disease using immunoblotting techniques. All the patients had fever of unknown origin and showed strong serological reactions to L bozemanii that cross-reacted with Rickettsia typhi, as determined by a standard indirect microimmunofluorescence assay. Sera analysed by western blotting reacted with 12-14 molecular components of L bozemanii with apparent molecular weights ranging from 14,000 to 94,000 daltons. These reactions compared well with a reference system using antisera of rabbits immunised with the same strain of Legionella. The three major cross-reactive components of R typhi were polypeptide antigens of 94,000, 67,000 and 43,000 daltons. It is concluded that western blotting can help in the differential diagnosis of patients with fever of unknown origin whose sera cross-react to L bozemanii and R typhi. PMID- 1752986 TI - Assessment of Diesse Ves-matic automated system for measuring erythrocyte sedimentation rate. AB - Measurement of the erythrocyte sedimentation rate (ESR) using a closed tube system reduces the biohazard risk to laboratory staff. The Diesse Ves-matic system offers manual or vacuum collection of blood into plastic tubes, automated mixing of the sample, and automated reading of the end point after 20 minutes of sedimentation. This system was compared with the 1977 Westergren ESR method of the International Council for Standardization in Haematology (ICSH) and with the 1988 ICSH undiluted ESR method. Manually collected Ves-matic samples showed good agreement with ICSH values, although there was a tendency to false low results at low ESR values which may represent dilution of plasma protein with excess citrate. Vacuum collected Ves-matic samples also showed good agreement with ICSH values, although there was a tendency to false high results which may reflect a change in the blood: citrate ratio caused by loss of anticoagulant diluent or vacuum from plastic tubes during storage. The Diesse Ves-matic system incorporates several improvements over previous technology and offers a safer, quicker, and more standardised ESR. PMID- 1752987 TI - Evaluation of the Ciba Corning Biotrack 512 coagulation monitor for the control of oral anticoagulation. AB - The Ciba Corning Biotrack 512 coagulation monitor requires a minimal degree of technical expertise to operate, and is already in use for near-patient testing. This study evaluated the monitor for possible use in decentralised control of oral anticoagulant treatment. The monitor compared well with Manchester Reagent, suggesting that it could be used in areas where this thromboplastin is used for centralised control. The inability of the monitor to allow for locally determined geometric mean normal prothrombin times in the calculation of the International Normalised Ratio (INR), and possibly the high International Sensitivity Index (ISI) of the thromboplastin used with the monitor, resulted in poor comparability with some other thromboplastins, particularly Thrombotest. These problems need to be addressed if the monitor is to be used for decentralised anticoagulant control. PMID- 1752988 TI - Bone marrow aplasia in B cell chronic lymphocytic leukaemia: successful treatment with antithymocyte globulin. AB - Pure red cell aplasia is a rare but well known association of chronic lymphocytic leukaemia (CLL). Pancytopenia due to bone marrow aplasia has not been previously described in CLL. A 42 year old man with B cell CLL became severely pancytopenic with bone marrow aplasia. Bone marrow culture resulted in a greatly reduced colony formation. High dose corticosteroids and intravenous immunoglobulin treatment were unsuccessful. Prompt and complete marrow recovery ensued after administration of antithymocyte globulin. PMID- 1752989 TI - Bleeding diathesis coincident with chronic myelomonocytic leukaemia. AB - Two important haematological problems were found in an otherwise healthy 78 year old man: chronic myelomonocytic leukaemia; and a complex, acquired, hyperfibrinolytic bleeding disorder characterized by prolonged coagulation times, deficiency of coagulation factors V, X, and XI, anti-thrombin III and proteins C and S, with high concentrations of circulating tissue plasminogen activator, and low concentrations of plasminogen activator inhibitor. There may be a causal relation between the two conditions, with the peripheral blood monocytes mediating the hyperfibrinolytic process by the abnormal production of tissue plasminogen activator, though no previous description of a similar association has been reported. PMID- 1752990 TI - Squamous cell carcinoma arising in endometriosis of the ovary. AB - Squamous cell carcinoma arising in ovarian endometriosis is extremely rare, but a case is reported in a 62 year old woman. If such an ovarian tumour is discovered evidence of teratoma, Brenner tumour, or endometriosis should be sought. Extensive sampling is mandatory as the developing tumour often overgrows the foci of endometriosis, thus obliterating evidence of its origin. PMID- 1752991 TI - Tuberous sclerosis and parathyroid adenoma. AB - Very little is known about the pathogenesis of tuberous sclerosis. Over the past 10 years, however, increasing numbers of reports on adenomatous diseases in association with tuberous sclerosis have been published. A case of hypercalcaemia and parathyroid adenoma in association with tuberous sclerosis is presented, of which there has been one such report published previously. This association might be another manifestation of this complex disease: it is therefore recommended that plasma calcium concentrations should be measured in such patients. PMID- 1752992 TI - Chronochemistry, rubber, and formalin. PMID- 1752993 TI - Declining necropsy rate. PMID- 1752994 TI - Defective erythropoiesis in myelodysplastic syndromes. PMID- 1752995 TI - Visceral leishmaniasis in human immunodeficiency virus disease. PMID- 1752996 TI - Periodontal aspects of osseointegrated fixtures supporting an overdenture. A 4 year retrospective study. AB - 196 Branemark implants in 86 consecutive patients rehabilitated by means of overdentures (6 upper jaws, 80 lower jaws) were observed longitudinally. In each jaw, only 2 implants were used to anchor the overdenture. 2 implants in the lower jaw showed some mobility at the abutment installation and were removed immediately. During the loading period (mean loading time 19.1 months ranging from 4 to 48 months), none of the implants showed any signs of non-integration. The marginal tissue reaction and plaque accumulation were monitored using conventional indices. Clinical methods and standardized radiographs were used to evaluate the bone level and density. The numbers of approximal surfaces without plaque (40%) or with gingival inflammation (55%) were almost constant throughout the study. The probing pocket depths remained within the range of 2.7 to 3.2 mm during the observation time, whereas the distance of the gingival margin from the top of the abutment clearly increased (from 1.8 to 2.9 mm). For loaded lower jaw implants connected to each other with a straight bar, a radiographic bone loss of 0.8 mm was observed during the first postsurgical year followed by a mean annual bone loss of less than 0.1 mm. For the "sleeping" fixtures, 50% less bone loss was recorded. For loaded but not interconnected implants in the upper jaw, the bone loss during the first 6 months reached 2.0 mm. The loss in marginal bone height did not clearly correlate with parameters such as the plaque index, the gingivitis index, the presence or absence of gingiva around the abutment, or the implant length. The present data, with an observation time up to 4 years, showed that the failure rate for Branemark implants supporting overdentures in the lower jaw can be limited to 1%. However, the use of 2 unconnected fixtures in the upper jaw cannot presently be advocated since considerable bone loss was observed. PMID- 1752997 TI - The microflora of periodontal sites showing active destructive progression. AB - 20 adult periodontitis (AP) subjects were examined every 2 to 4 months and microbiological samples were collected and cultured when 2 mm or more loss of attachment (active sites) was detected by 2 examiners. Similar sites in which no progressive destruction was observed (control sites) also were sampled in the same subjects. By lambda-analysis, there was no statistically significant difference in floras of active (42 sites from 12 subjects) and control (36 sites from 12 subjects) sites or between the floras of the active and control sites and of 63 samples from 22 AP subjects that were examined previously in a cross sectional study. By paired t test, no microbial species had a significantly greater association with active than with control sites. The only species that were detected in one or more samples from all subjects with active sites were Wolinella recta, Fusobacterium nucleatum, and Peptostreptococcus micros. Porphyromonas gingivalis and 9 other taxa were isolated from one-half or more of the persons with active sites. The composition of microbiological floras of all periodontitis samples was statistically significantly different from that of subjects with healthy gingiva. The composition of microfloras of sites in subjects with naturally-occurring gingivitis was intermediate between that of subjects with healthy gingiva and that of active and control sites in AP subjects. PMID- 1752998 TI - Marginal bone loss in 16-year-old Swedish adolescents in 1975 and 1988. AB - The study was designed to compare the prevalence of marginal bone loss in 2 cohorts of 16-year-old adolescents, born in 1959 and 1972, respectively. Bitewing radiographs from 400 adolescents in each group were evaluated and the presence of bone loss (distance between the cemento-enamel junction and the alveolar crest greater than 2 mm), calculus, restorations and proximal dental caries were recorded. The prevalence of bone loss was 3.5% in 1975 as well as in 1988. Bone loss was found most frequently at the mesial and distal surfaces of the first maxillary molar. The prevalence of calculus was 12% in 1975 and 7% in 1988. The mean DFS for proximal surfaces was 3.1 in 1975 and 0.8 in 1988. No statistically verified dependence was found between bone loss and calculus, or bone loss and proximal caries. PMID- 1752999 TI - Periodontal condition of pregnant women assessed by CPITN. AB - The periodontal conditions of 2424 pregnant and 1565 non-pregnant women were assessed according to the community periodontal index of treatment needs (CPITN). The aim of this survey was to obtain information which is necessary for the planning of preventive programs of periodontal disease for pregnant women. 95% of the pregnant women and 96% of the non-pregnant women had some signs of periodontal disease. The % of pregnant women having 4 or 5 mm pockets was significantly higher than that of non-pregnant women, increased with the month of pregnancy, reached a maximum of 31% in the 8-month group, but decreased to the control level in the 9-month group. These changes were interpreted to suggest that the increase of pocket depth during pregnancy was caused by gingival enlargement rather than by periodontal destruction. The results show that pregnant women had a healthier periodontal condition when compared with non pregnant women, i.e., the number of sextants with healthy periodontal tissues was higher, the % of people having deep pockets (6 mm or deeper) was lower, and the need for prophylaxis was lower in pregnant than in non-pregnant women. These findings suggest that a special program of periodontal disease prevention for pregnant women is not necessary. PMID- 1753000 TI - Application of matched pair procedures to site-specific data in periodontal research. AB - Application of standard statistical procedures to site-specific data in periodontal research is invalid unless site-to-site dependencies are accounted for. In this paper, we present the adjustments required for valid application of matched pair procedures, including the paired t-test and McNemar's chi 2 test for correlated proportions. Examples are given involving data arising from: (1) the comparison of pre- and post-treatment clinical measurements; (ii) split-mouth protocols. PMID- 1753001 TI - Proximal attachment loss in Swedish adolescents. AB - The present study describes periodontal conditions in 22 adolescents with proximal attachment loss greater than or equal to 2 mm (AL) and 22 matched referents without AL, all identified in a cross-sectional study of 570 16- and 18 year-old. The cases were followed for 3 years and the referents for 1 year while they were in the care of an organized dental health system. With the exception of 1 case with Morbus Hodgkin, the case and referent groups had a similar background with respect to general health and participation in the dental health program. Bleeding on probing was found at AL sites in 12 of the cases and at corresponding sites in 4 referents. 2 cases had a history of eruption disorders at the AL sites, 1 case had experienced a defective filling and 1 had a root fissure at the AL sites. At re-examinations after 1 and 3 years, 10 out of 21 earlier identified AL cases did not meet the criterion of 1 or more sites with AL greater than or equal to 2 mm. None of the cases showed progression greater than or equal to 2 mm of the lesions. In 1 case, the number of AL sites increased during the period. 4 of the cases harboured Actinobacillus actinomycetemcomitans (A.a.) at AL sites in year 1 and 3 in year 3. 8 of the cases and 4 referents had antibodies specific for A.a.-leukotoxin. The 2 most severe cases, in terms of number of sites with AL, showed bleeding at 1 or more of the AL sites, harboured A.a. at these sites and had serum titers against A.a.-leukotoxin. PMID- 1753002 TI - Acute necrotizing ulcerative gingivitis is associated with attachment loss. AB - Acute necrotizing ulcerative gingivitis (ANUG) has been generally considered as a gingivitis. However, clinical impressions suggest that periodontal attachment loss is one of the sequelae of the disease. This study was designed to investigate the extent of probing attachment loss detectable following resolution of the acute phase of the disease. 13 patients (3 male, 10 female) aged on average 22.7 years were studied. The presence of interdental soft tissue cratering was used to determine whether a site was previously affected by ANUG. ANUG sites were compared with other sites using a paired Student t-test (N = 13). Patient mean probing attachment level was greater for ANUG sites (2.2 +/- 0.9) than for the mean of all other sites (0.8 +/- 0.7). It is concluded that greater loss of probing attachment is associated with sites affected by ANUG than with other sites studied. PMID- 1753003 TI - Reproducibility of attachment level measurements with two models of the Florida Probe. AB - Clinical assessment of the progression of periodontitis is based on the measurement of periodontal probing attachment levels over time. In calculating these changes, duplicate measurements from fixed reference points, including cemento-enamel junctions and acrylic stents, have been used to assist in detecting progressive disease. The Florida Probe has been previously shown to improve the reproducibility of these measurements when used with an acrylic stent. The objective of the present study was to evaluate the reproducibility of 2 models of the Florida Probe, the original stent model and the modified disk model, in measuring attachment level. The disk probe differs from the stent probe in that it uses the occlusal surface of the tooth as a static reference point in calculating changes in attachment level measurements. In 10 subjects, sites were probed 2 x by 2 examiners using both types of probe. Standard deviations and intra- and inter-examiner correlations were calculated. These results demonstrate that the new disk probe yields reproducible measurements similar to the stent probe and is therefore suitable for use in longitudinal clinical studies. PMID- 1753004 TI - A new method to assess damaging effects on the gingival tissues of non-surgical instrumentation. AB - A method of assessing the damaging effects of non-surgical instrumentation was developed. To test the technique, the effect of cavitational activity in the water supply of an ultrasonic scaler was investigated in an in vivo situation. Using a replication technique for the scanning electron microscope, it was shown that the water supply of the ultrasonic scaler caused superficial disruption of the surface of the gingiva, distant from the area of damage caused by mechanical contact. The results indicated that further investigations of this phenomenon using the technique were required. PMID- 1753005 TI - Subgingival irrigation in the maintenance phase of periodontal therapy. PMID- 1753006 TI - Cell-seeding. PMID- 1753007 TI - Antiarrhythmic drug therapy: a continuously evolving field. PMID- 1753008 TI - Crime, misdemeanor, and arrhythmia decoding CAST. PMID- 1753009 TI - Electrophysiologic mechanisms for ventricular arrhythmias in left ventricular dysfunction: electrolytes, catecholamines and drugs. AB - Cardiac arrhythmias are generated as the result of disorders of automaticity or of impulse conduction. Regardless of the mechanism, calcium is likely to be involved, although calcium antagonists are rarely useful antiarrhythmics in ventricular arrhythmias. Myocardial cells that do not ordinarily initiate action potentials may do so when they are partially depolarized, giving rise to an ectopic focus. Early afterdepolarizations (EADs) are also induced in cardiac cells by partial depolarization, whereas delayed afterdepolarizations (DADs) are induced by Ca++ overloading. EADs may be the initiating mechanism of torsade de pointes, a complication of QT prolongation associated with quinidine therapy. Both in the animal model and in humans, treatment with magnesium, isoproterenol, or pacing, all of which suppress EADs, will also suppress torsade de pointes. Ventricular tachycardia is a manifestation of ordered re-entry, and may be exacerbated by antiarrhythmics, especially class 1c drugs. In the individual patient, prediction of proarrhythmia is not possible. The risk of proarrhythmia is increased in patients with episodes of sustained ventricular tachycardia or with significant left ventricular dysfunction. PMID- 1753010 TI - Pharmacology and pharmacokinetics of amiodarone. AB - Amiodarone is a unique antiarrhythmic agent originally developed as a vasodilator. Classified electrophysiologically as a Type III antiarrhythmic, it also has both nonspecific antisympathetic and direct, fast channel-membrane effects. Hemodynamic effects of orally administered amiodarone (a negative inotropic agent) are usually negligible, and are usually compensated for by induced vasodilation. Effects on thyroid and hepatic function may help to explain some of the unique pharmacologic as well as toxicologic effects of the drug. Amiodarone is poorly bioavailable (20-80%) and undergoes extensive enterohepatic circulation before entry into a central compartment. The principal metabolite, mono-n-desethyl amiodarone is also an antiarrhythmic. From this central compartment, it undergoes extensive tissue distribution (exceptionally high tissue/plasma partition coefficients). The distribution half-life of amiodarone out of the central compartment to peripheral and deep tissue compartments (t1/2 alpha) may be as short as 4 hours. The terminal half-life (t1/2 beta) is both long and variable (9-77 days) secondary to the slow mobilization of the lipophilic medication out of (primarily) adipocytes. A pharmacokinetically based loading scheme is described, and data suggesting a role for routine amiodarone plasma levels are presented. PMID- 1753011 TI - Hemodynamic effects of antiarrhythmic drugs. PMID- 1753012 TI - Sudden death in congestive heart failure. AB - Despite significant advances in recent years in the diagnosis and treatment of congestive heart failure, sudden unexpected cardiac death is still considered a major epidemiologic problem among those patients. This article lists some of the predisposing factors to the development of cardiac arrhythmias and sudden death in patients with congestive heart failure. These include electrolyte or autonomic nervous system inbalance, the use of certain anti-arrhythmic drugs, or intermittent myocardial ischemia. This paper shows that an advanced degree of left ventricular dysfunction and the preference frequent or complex ventricular arrhythmias appear to be major predictors of total and sudden mortality among patients with congestive heart failure. A screening of 24 hours ambulatory Holter monitor recording appears to be useful in identifying patients at risk of sudden cardiac death. PMID- 1753013 TI - Identification of patients at risk for sudden death in congestive heart failure. PMID- 1753014 TI - Amiodarone therapy guided by electrophysiologic testing: an update. PMID- 1753015 TI - Left ventricular dysfunction and ventricular arrhythmias: reducing the risk of sudden death. PMID- 1753016 TI - Long-term treatment of ventricular tachycardia with amiodarone in presence of severe left ventricular dysfunction. AB - A group of 34 consecutive patients with coronary artery disease (n = 29) or dilated cardiomyopathy (n = 5) (3 women, 31 men, age 38-80 yr) who had severely impaired left ventricular function (left ventricular ejection fraction less than or equal to 40%) and high-grade ventricular ectopic activity (sustained or nonsustained ventricular tachycardia or ventricular fibrillation) were treated with amiodarone (mean dose: 206 mg/d) and followed for 1-117 (mean: 49) months. In the total group, there were seven sudden deaths, five deaths due to pump failure, one non-cardiac death, and two successful heart transplantations during follow-up. Thus the annual cardiac mortality in these carefully selected and followed patients was 8, 6%, the annual cardiac event rate was 10, 1%. The cumulative cardiac survival-rate was 62% after 5 years and 41% after 10 years. In five patients, treatment was interrupted after 10 to 43 months, three of the patients were alive at follow-up and two suffered cardiac death, resulting in an annual cardiac death rate of 12% in this subgroup of treatment. Based on the results of this retrospective analysis we conclude that in patients with low left ventricular ejection fraction and nonsustained or sustained ventricular tachycardia treated with low dose amiodarone, mortality was unexpectedly low. Thus, it may be the antiarrhythmic treatment to be considered in patients with ventricular tachycardia and severe left ventricular dysfunction. PMID- 1753017 TI - Ventricular arrhythmias associated with congestive heart failure: the role for amiodarone. PMID- 1753018 TI - Survival of patients with nonsustained ventricular tachycardia and impaired left ventricular function treated with low-dose amiodarone. PMID- 1753019 TI - Thyrotropin-releasing hormone-immunoreactive projections to the dorsal motor nucleus and the nucleus of the solitary tract of the rat. AB - Thyrotropin-releasing hormone-immunoreactive nerve terminals heavily innervate the dorsal motor nucleus and nucleus of the solitary tract, whereas cell bodies containing thyrotropin-releasing hormone residue most densely in the hypothalamus and raphe nuclei. By using double-labeling techniques accomplished by retrograde transport of Fluoro-Gold following microinjection into the dorsal motor nucleus/nucleus of the solitary tract combined with immunohistochemistry for thyrotropin-releasing hormone, it was demonstrated that thyrotropin-releasing hormone-immunoreactive neurons projecting to the dorsal motor nucleus/nucleus of the solitary tract reside in the nucleus raphe pallidus, nucleus raphe obscurus, and the parapyramidal region of the ventral medulla, but not in the paraventricular nucleus of the hypothalamus. The parapyramidal region includes an area along the ventral surface of the caudal medulla, lateral to the pyramidal tract and inferior olivary nucleus and ventromedial to the lateral reticular nucleus. Varying the position of the Fluoro-Gold injection site revealed a rostral to caudal topographic organization of these raphe and parapyramidal projections. PMID- 1753020 TI - Parallel thalamic activation of the first and second somatosensory areas in prosimian primates and tree shrews. AB - In Tupaia belangeri and Galago senegalensis, microelectrode recordings immediately after ablation of the representation of the forelimb in the midportion of the first somatosensory area, S-I, revealed that all parts of the second somatosensory area, S-II, remained highly responsive to cutaneous stimuli. In this way, prosimian primates, close relatives of simian primates, and tree shrews differ markedly from monkeys in which S-II is deactivated by comparable ablations, and resemble such mammals as cats and rabbits in which S-II also remains highly responsive following ablations in S-I. Thus, it appears that the generalized mammalian condition is that S-I and S-II are independently activated via parallel thalamocortical pathways. A dependence of S-II on serial connections from the thalamus to the S-I region and then to S-II apparently evolved with the advent of anthropoid primates, and may be present only in monkeys and perhaps other higher primates. PMID- 1753021 TI - Neuronal differentiation and maturation in the mouse trigeminal sensory system, in vivo and in vitro. AB - We have isolated and characterized four monoclonal antibodies (mAbs B33, E1.9, B30, and B10) that recognize mouse trigeminal sensory neurons at specific times during development. These antibodies permit the study of neuronal differentiation, axon outgrowth, and neuronal maturation in the trigeminal sensory system. With B33, we can follow migrating neural crest and placode cells into the anlagen of the trigeminal ganglion. E1.9 immunoreactivity marks neuronal differentiation and appears in the central nervous system at embryonic day 8.5 (E8.5) and in the peripheral nervous system at E9, E1.9 and B30 show the axonal outgrowth of trigeminal sensory neurons and reveal the pioneering of the peripheral tracts by an early population of ganglionic neurons. At this stage, in the central nervous system, mesencephalic trigeminal neurons are also E1.9 and B30 positive as they migrate to their final location in the rostral metencephalon. B30 and B10 allow us to follow the maturation of these neurons. Also, in about 1% of the embryos, we identified mispositioned or misrouted trigeminal neurons. Furthermore, these biochemical markers facilitate the study of neuronal development in vitro. We find that, based on morphological and biochemical criteria, the maturation of trigeminal neurons in culture is target independent. PMID- 1753022 TI - Meeting the challenge of cancer care and prevention in Europe. PMID- 1753023 TI - Nursing research: is there an obligation on subjects to participate? AB - Studies of the ethics of medical and nursing research have focused principally on the more practical issues to do with the research process, such as informed consent and protection of subjects from harm. A more fundamental question, which is often overlooked, is whether individuals are under any sort of obligation to participate as subjects in nursing research in the first place. The conclusions which nurses reach on this issue will help establish the overall moral climate in which nursing research is conducted. In this paper, three models of such an obligation are explored; one based on a notion of payment, one centred in the social contract, and one which seeks to establish an unconditional obligation. Each of these is seen to be flawed in various respects. The delicate and potentially conflicting relationship between obligation and consent is then briefly examined. In conclusion, it is argued that the notion of a 'moral claim' on participation in research is an ethically more acceptable approach than any strict sense of obligation. PMID- 1753024 TI - Case study of learning milieux: the modifying effect of the workplace. AB - In examining the clinical environment that may influence the first-year college graduate's attitudes toward continuing learning, four case studies were conducted in hospitals within the Illawarra Area Health Service, New South Wales. The exploratory research attempts to determine the extent to which desired educational changes occur and where improvements could be made to the educational process. This paper reports the research findings. PMID- 1753025 TI - An experiment in the development of empathy in student nurses. AB - Student nurses were assessed for their specific interview behaviour with patients after experiencing an empathetic training and a psychological-mindedness experience. The results show that empathy was not increased or decreased. The reasons for the experimental findings are discussed. PMID- 1753026 TI - An analysis of the concept of comfort. AB - Comfort is a term that has a significant historical and contemporary association with nursing. Since the time of Nightingale, it is cited as designating a desirable outcome of nursing care. Comfort is found in nursing science, for example in diagnostic taxonomies, and in references to the art of nursing, as when practice is described. Roy, Orlando, Watson, Paterson and others use comfort in major nursing theories. The term can signify both physical and mental phenomena and it can be used as a verb and a noun. However, because comfort has many different meanings, the reader has had the burden of deciding if the term is meant in one of its ordinary language senses or if its context reveals some special nursing sense. The purpose of this paper is to analyse the semantics and extension of the term 'comfort' in order to clarify its use in nursing practice, theory and research. The semantic analysis begins with ordinary language because the common meanings of the term are the primary ones used in nursing practice and are the origin of technical nursing usages. Comfort is discussed as the term is found in nursing, including texts, standards of care, diagnoses and theory. An account of patient needs assessment is used to cull three technical senses of the term from its ordinary language meanings. After contrasting these senses in order to justify their separateness, they are shown to reflect differing aspects of therapeutic contexts. Defining attributes of the three senses are then explicated and presented in table format. The last section of the paper addresses some of the ways that the extensions of the senses can be measured. PMID- 1753027 TI - Chronic sorrow: analysis of the concept. AB - Emotionally close relationships can be disrupted at any time in the life cycle. When a relationship of attachment is disrupted following an event that renders a loved one forever changed from the hoped-for child or from the known person, recurrent sadness, or chronic sorrow, is a frequently encountered response. The genesis of sadness is one's recognition of a negative disparity between the person who was known prior to the onset of disability (or the imagined, hoped-for child) and the now-disabled person. Though each episode of sadness resolves somewhat over time, renewed recognition of a negative disparity in the disabled loved one triggers sadness again. Besides being recurrent, the sadness of chronic sorrow is also permanent, variable in intensity between situations and persons, and interwoven with periods of neutrality, satisfaction and happiness. The concept is analysed and contrasted with the prevalent model of linear, time-bound grief. PMID- 1753028 TI - The health meanings and practices of older Greek-Canadian widows. AB - Folk health and illness beliefs and practices were abstracted from a large-scale study of older Greek-Canadian widows conceptualized within Leininger's theory of Cultural Care Diversity and Universality using ethnographic, ethnonursing, and life health-care history methods. Data were collected using observation participation and interviews in three Greek-Canadian communities with 12 widowed key informants and 30 general informants. Interview inquiry guides, Leininger's Life History Health Care Protocol, and field journal recordings assisted data collection. Data were analysed using Leininger's phases of analysis for qualitative data. A major health theme which was abstracted from the raw data and patterns was: health for Greek-Canadian widows meant a state of well-being, ability to perform daily role activities, and avoidance of pain and illness. The findings, which also included folk health care and illness beliefs and practices, will stimulate future nursing research related to health and nursing care of people of diverse cultures. PMID- 1753029 TI - Coping and life satisfaction in elderly women with osteoarthritis. AB - The relationships among illness-related stress and emotions, coping strategies, socio-economic status and life satisfaction of 90 elderly women with osteoarthritis were explored in this descriptive, correlational study. Results of self-report interview data indicated that the women experienced both positive and negative emotions in relation to their day-to-day life with osteoarthritis. The coping behaviours used to manage the perceived stress of osteoarthritis included confrontive, palliative and emotive strategies. Path analysis supported a significant and positive relationship between coping and life satisfaction and between objective and subjective measures of life satisfaction. PMID- 1753030 TI - A reassessment of nurses' attitudes towards stroke patients in general medical wards. AB - This paper summarizes a research study inquiring into the attitudes of qualified nursing staff and nursing auxiliaries towards stroke patients in general medical wards. The survey was undertaken on eight mixed-sex general medical wards in a large general hospital. All wards are used for clinical nursing experience for nurses in training. Each of the wards, despite having a particular interest in one or more medical specialities, regularly admit patients following stroke. All nurses were therefore familiar and in regular contact with this particular client group. A Likert scale with demonstrated reliability and validity was employed as the data collection instrument. Results indicated that nurses were largely ambivalent in their attitudes towards stroke rehabilitation. The patterns of responses indicate that the nurses who have the more positive attitudes about stroke patients consider that they have a role in stroke rehabilitation and that they value the nursing contribution. The nurses with less positive attitudes towards stroke patients see stroke patients as unco-operative and demanding. The findings suggest the need for specific education for the role of the nurse as a rehabilitator. PMID- 1753031 TI - Health promotion of older adults: perceived barriers. AB - The purpose of this descriptive study was to examine the perceptions of rural men and women, ages 50 to 70 years, regarding barriers to health promotion in the treatment of a chronic disease entity--hypertension. Orem's constructs of self care provided the theoretical framework for the study. Specific study aims were to (a) identify health belief/values, (b) assess perceptions of self-care abilities, (c) determine relative risk through health appraisal, and (d) describe phenomenological perceived barriers to health promotion as a lived experience. Major findings indicated no relationship between health beliefs/values and self care. The health value scores of females for all four subscales were somewhat higher than the scores for males. Average, appraised and achievable ages for relative risk of dying from all causes were significant for men. Phenomenological themes revealed diet, weight and medication usage to be two factors associated with perceived barriers. Small sample size and voluntary participation limited generalization. Nursing implications included the need for (a) greater assessment of the influence of perceived barriers, (b) better approaches to health teaching, and (c) more appropriate design of educative--supportive nursing interventions for facilitating client self-care. PMID- 1753032 TI - Models of nursing: their relevance to the care of elderly people. AB - The adoption of nursing models has become widespread throughout the profession with little empirical evidence of their usefulness or critical evaluation. This paper gives an overview of the issues surrounding the development and use of models and presents research data which indicates that one model (Roper, Logan & Tierney's Activities of Living) is problematic in the long-term care of the elderly. The characteristics of this model which are problematic are common to other models and have relevance for other areas of nursing. PMID- 1753033 TI - The sources of a practice code of ethics for nurses. AB - Interviews with a convenient sample of 27 master's-prepared nurses working in two clinical settings revealed that none of them knew the content of the American Nurses' Association Code for Nurses. A content analysis developed four sensitizing experiences that were sources for their code of nursing practice. These were categorized as: (a) clinical, (b) personal, (c) research, and (d) professional socialization as a student. PMID- 1753034 TI - In defence of Cartesian dualism and the hermeneutic horizon. AB - In this paper, the author proposes to consider the intricate interplay between the art and science of nursing. The caring role, intrinsic to the meaning of the word 'nurse' constrains nursing under the rubric of the arts, while nursing that embraces high technology constrains the discipline under the rubric of science. Thus, the traditional dichotomy that obtains between the arts and sciences seriously complicates the notion of nursing. As a science, nursing adopts the materialist theory of the mind that endorses the inseparability of mind and body. However, as an art, nursing is more closely aligned with dualist interactionism which considers the mind and body to be separate, interacting entities. Nursing is a caring profession, the mastery of which rests on the mastery of the therapeutic relationship which, in turn, implies mastery of holistic nursing care. While the concept of holism implies caring for the 'whole' person in body, mind and spirit, such acknowledgement of the mental and spiritual components of personhood, immediately invites the entry of dualism into our theoretical discourse. Thus, rejection of dualism consigns nursing to theoretical impoverishment and therapeutic emasculation. The contentious question is therefore: Is the theoretical destiny of nursing one of theoretical impoverishment, therapeutic emasculation, and permanent consignment to professional ignominy--and all for the sake of an inconvenient soul? PMID- 1753035 TI - Using a manpower database to model nurse turnaround and return to service. AB - A manpower database for nurses employed by the Department of Health and Social Services in Northern Ireland has been developed. This database contains information on all nurses employed between March 1977 and July 1988 and consists of data on all posts held in this period, including breaks in service. The authors show how these data may be used to analyse the durations of spells in post and spells out of service prior to departure to a number of destinations for the sister and staff nurse grades. The results are presented in a graphical format which enables us to evaluate the relative proportion of departures to each destination and at what stage in service these departures are likely to occur. Such a methodology provides a valuable tool for the nurse manpower planner, and utilizes personnel data which are routinely collected by most health authorities. PMID- 1753036 TI - Feedback--debate about triage in accident and emergency departments. PMID- 1753037 TI - Unipolar depression in the aged: determinants of familial aggregation. AB - Late-onset depression (greater than or equal to 60 years) is believed to be less associated with a risk of depression in first-degree relatives than early-onset depression. However, family studies in elderly probands fitting the current methodological standards of family studies are not available. The reported family study in geriatric inpatients with unipolar major depression (n = 92) supported the proposed relationship between age at onset and the proposed familial loading. A comparison to families of age-matched controls (n = 33) revealed that relatives of probands with late-onset depression are still at an increased risk of depression. However, late-onset depression was not more common in families of probands with late-onset depression than in families of probands with early-onset depression. Besides the age at onset, the recurrence of depressive episodes defined distinct patterns of familial aggregation. PMID- 1753038 TI - The interrelatedness of observed behavior of depressed patients and of a psychiatrist: an ethological study on mutual influence. AB - The interaction of 61 severely depressed hospitalized patients and a psychiatrist was studied during a clinical interview. Interactional processes were defined by the use of ethological methods. Various observed behaviors were clustered on the basis of statistical criteria, yielding behavior factors of the patients and of the psychiatrist. The present paper deals with the organization of the psychiatrist's behavior and the interrelatedness of the patients' and the psychiatrist's behavior. Analysis of the behavior of the psychiatrist revealed seven factors: restlessness-1 (head, leg movements, object touching), restlessness-2 (body touching, head movements), speech (speech, gesticulating, yes and no movements), active listening (intensive body touching and hand movements), turn-taking (leg movements and gesticulating during listening), encouragement (back-channel behavior and yes-nodding), and change-looking (looking and head movements). Within the constraints of studying interactions which are bidirectional, it was found that restlessness-2, speech, encouragement and active listening of the psychiatrist could be 'predicted' from observed behavior of the patients (multiple regression model). The psychiatrist's behavior was related both to the severity of depression and to observed behavior not directly associated with severity. The psychiatrist's behavior was more strongly related to that of the more severely depressed patients than to that of the less severely depressed patients. These results contribute to an understanding of the behaviors displayed and elicited by depressed patients during a first encounter with a stranger. PMID- 1753039 TI - Can winter depression be prevented by light treatment? AB - The administration of light at the development of the first signs of a winter depression appears to prevent it from developing into a full-blown depression. No patient from a group of 10 treated in this way developed any signs of depression during the rest of the winter season, while five of seven patients from a control group became depressed and needed treatment during the winter season. PMID- 1753040 TI - Ergopsychometry in depressive patients. AB - Thirteen patients with major depressive disorder, 25 patients with dysthymia and 12 healthy controls underwent ergopsychometric testing. The effect of self-paced and set-paced load on mood, vigilance and perseveration tendency was recorded. Within the clinical groups, various types of load seemed to result mainly in variations in mood. Dysthymics reacted to monotonous load with a deterioration in mood and reacted to load under time pressure with an improvement in mood. Patients with major depressive disorder displayed an amelioration in mood throughout the whole experiment regardless of which particular stressor was being employed. In healthy patients, load did not appear to produce any significant change in mood. PMID- 1753041 TI - The effects of depression and age on the Horne-Ostberg morningness-eveningness score. AB - Effects of depression and age on the Horne-Ostberg morningness-eveningness scale in human volunteers were assessed. Thirty-nine healthy outpatients with current DSM-IIIR depression, free of recent substance abuse or confounding medications, were compared to 39 age- and sex-matched controls. Patients reported greater 'eveningness' than controls (P = 0.014, Wilcoxon signed-ranks test). There was multimodality in the distribution of Horne-Ostberg scale scores in the depressed group, but a normal distribution in controls. Pearson's correlation of age vs. Horne-Ostberg score was positive (r = 0.42-0.55). Depression and age influence the Horne-Ostberg score. Potential multimodality of circadian phase in the depressed group deserves further study. PMID- 1753042 TI - Prevalence of postural hypotension at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort. AB - OBJECTIVE: The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH). DESIGN: Baseline cross-sectional analysis of the 4,736 persons randomized in the Systolic Hypertension in the Elderly Program (SHEP). SETTING: A randomized multi-center double-blind outpatient clinical trial of the impact of treating ISH. PARTICIPANTS: Men and women age greater than or equal to 60 years with the systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg. MEASURES: Medical histories were obtained using interviewer-administered, standardized clinical history forms. At entry into the study, seated and standing BP was measured by certified BP technicians using a random zero sphygmomanometer. Postural hypotension (PH) was assessed at 1 and 3 minutes after the participant arose from a seated position. MAIN RESULTS: PH was found in 10.4% of participants at 1 minute and in 12.0% of participants at 3 minutes. 5.3% of participants demonstrated PH at both time intervals while 17.3% demonstrated PH at either or both of the time intervals. Factors significantly (P less than 0.05) associated with the presence of PH were higher mean SBP and a lower mean body mass index. CONCLUSIONS: Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute standing measures of BP, and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used. Cross sectional data analysis indicated that PH, in healthy community-dwelling older persons with ISH, may not be associated with a history of disorders or problems usually thought to be related to PH. However, prospective data are needed to determine the prognostic significance of PH, and whether one or multiple measurements carry more significance. PMID- 1753043 TI - Effects of exercise training on bone density in older men and women. AB - OBJECTIVES: To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults. DESIGN: Randomized controlled trial with subjects assigned to either an aerobic exercise condition, non-aerobic yoga, or a wait list non-exercise control group for 4 months. Aerobic fitness and bone density were evaluated in all subjects at baseline (Time 1) and after 4 months (Time 2). A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise, followed by another evaluation (Time 3). All subjects were then given the option of 6 additional months of aerobic exercise, after which they had a fourth evaluation (Time 4). SETTING: An outpatient exercise rehabilitation facility at a large, major medical center. SUBJECTS: One-hundred one healthy men (n = 50) and women (n = 51) over age 60 (Mean age = 67.0), recruited from the community. INTERVENTION: The exercise program included stretching, cycle ergometry, and walking three times per week for 60 minutes throughout the course of the study. OUTCOME MEASURES: Aerobic fitness (VO2max) as assessed by cycle ergometry, and bone density (bone mineral content) measured by single photon absorptiometry. RESULTS: Subjects achieved a 10%-15% increase in VO2max after 4 months of exercise training, and 1%-6% further improvement with additional training. Aerobic fitness was associated with significant increases in bone density in men, but not women, who maintained aerobic exercise for 14 months. PMID- 1753044 TI - Prevalence and characteristics of nursing home-acquired infections in the aged. AB - OBJECTIVES: This study provides estimates of the prevalence of infections in all patients from a representative sample of 53 Maryland nursing homes; identifies risk factors for these infections; and describes diagnostic procedures carried out. METHODS: The records of 4,259 patients in a stratified random sample of 53 Maryland nursing homes were reviewed for diagnostic procedures, medical, functional, and behavioral status. Infections were identified by signs, symptoms, and laboratory findings. RESULTS: Study patients were characteristic of aged patients in US nursing homes. The prevalence of infections actually acquired in the nursing home (80% of all infections) was 4.4%. Multivariate analysis revealed that skin infections (35% of nursing home-acquired infections) were associated with skin ulcers and inversely with urine incontinence. Fevers of uncertain source (13%) were associated with bladder catheters. Symptomatic urinary infections (12%) and lower respiratory infections (12%) were associated with bedfast status, and the latter with tracheostomy and lung disease. Skin ulcers, urethral catheters, and bedfast status were markers for nursing home-acquired infection. The prevalence of infection in patients with all three markers was 32%; in patients with none, 2%. Fewer than a quarter of the four most common nursing home-acquired infections received an evaluation which met minimal diagnostic criteria established by a panel of infectious disease specialists and geriatricians. Patients with dementia, those in large homes (greater than 150 beds), and those in urban homes were less likely to be evaluated in a manner meeting these criteria. CONCLUSIONS: Use of three characteristics (ie skin ulcers, urethral catheters, bedfast status) to identify patients at risk for nursing home-acquired infections may allow targeted infection surveillance and prevention programs. In addition, nursing home-acquired infections are not evaluated uniformly across patients and facilities, suggesting the need to establish, through further study, guidelines for such evaluations. PMID- 1753045 TI - Comparing sources of drug data about the elderly. AB - OBJECTIVE: This project assessed the extent of agreement between drug-taking data obtained from an in-home assessment and that obtained from an automated outpatient pharmacy system and from a mail questionnaire. DESIGN: The underlying assumption is that an in-home assessment provides the most complete information (criterion standard) about the prescription medications being taken. The drug data from the mail questionnaire and automated outpatient pharmacies were compared with that from the in-home assessment by use of t tests and measures of sensitivity, specificity, and positive predictive value. SETTING: Kaiser Permanente, Northwest Region, a prepaid group practice HMO. PARTICIPANTS: All elderly HMO members enrolled in the Social HMO demonstration project who had a comprehensive assessment within 30 days of returning a mail questionnaire between March 1986 and March 1988 (n = 83 frail elderly). MAIN OUTCOME MEASURES: The number of medications currently being taken and the number of different therapeutic classes of drugs being taken per elderly HMO member. MAIN RESULTS: The in-home assessment and the automated prescription system closely agreed on the number of different medications and the different therapeutic classes of prescription drugs being taken. The in-home assessment and mail questionnaire were in less agreement. Agreement was less for non-prescription drugs. CONCLUSIONS: An automated prescription system is an adequate source of information about the prescription drugs currently being taken by frail elderly HMO enrollees with a prepaid prescription drug benefit. PMID- 1753046 TI - Teaching physical diagnosis in the nursing home: a prospective, controlled trial. AB - STUDY OBJECTIVE: To investigate the suitability of the nursing home as a site for teaching physical diagnosis to second-year medical students. DESIGN: Prospective comparison of teaching sessions in the nursing home to concurrent control sessions in acute care wards. SETTING: Nursing Home Care Unit (NHCU) and acute care hospital wards of a Veterans Affairs Medical Center. PATIENTS: Sessions with 38 NHCU patients and 68 hospital patients. MEASUREMENTS AND MAIN RESULTS: Patient interviews and student questionnaires were used to obtain responses on a 1-10 scale (1 = poor, 10 = excellent). Patient responses were very favorable in both settings for overall quality of experience (mean score NHCU vs control: 8.8 vs 8.6) and willingness to participate again (8.4 vs 8.2). Student ratings showed no significant differences for patient attitude (7.4 vs 8.4) or quality of exam (7.2 vs 7.7) while quality of history (6.0 vs 7.6) and overall quality of session (7.6 vs 8.6) were rated higher (P less than 0.05) for the control sessions. Students rated both environments highly (8.6 vs 8.4) but reported that fewer NHCU sessions were interrupted (15% vs 25%) or disrupted by noise (6% vs 30%, P less than 0.005). CONCLUSIONS: Advantages of the nursing home include readily available patients who view participation favorably, instructive physical findings, and a suitable environment. However, students rate the quality of the histories obtained there lower. This problem could be addressed by more careful patient selection and greater emphasis by course instructors on other goals of the history in addition to exploring the chief complaint. PMID- 1753047 TI - The prevalence of undiagnosed protein-calorie undernutrition in a population of hospitalized elderly patients. AB - OBJECTIVE: To determine the extent to which patients with objective signs of malnutrition had been diagnosed as such by physicians and the diagnosis documented in the medical record. DESIGN: Cross-sectional. SUBJECTS: All non critically ill patients (n = 121) aged 70 years or older admitted to an Oslo hospital during a 3-week period. METHODS: Compared problem list and other elements of the medical record with observations of height, weight, triceps skinfold, midarm circumference, and arm-muscle circumference made on first weekday in hospital. Serum albumin available on 66 subjects. MAIN RESULTS: Nine patients had weight/height ratios below 60% of normal, 16 patients between 60% and 75%, and 41 patients between 74% and 90% of normal. Of these 66 patients, only 24 were recognized as malnourished on admission, only five received nutritional support, and none was diagnosed as having malnutrition at the time of discharge. CONCLUSIONS: Malnutrition is underdiagnosed and undertreated. The consequences of this are likely to be deleterious to health. PMID- 1753048 TI - Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? AB - OBJECTIVE: To study the incidence and the risk factors of adverse drug reactions. DESIGN: Multicenter survey. SETTING: Hospitalized care: 22 internal medicine and 19 geriatric wards. PATIENTS: All patients (n = 9,148) consecutively admitted during two observation periods of 2 months. MAIN OUTCOME MEASURE: Incidence of adverse drug reactions. RESULTS: The mean age was 67.1 +/- 0.17 years (median 72); the mean duration of hospital stay was 18.1 +/- 0.19 days (median 14). Each patient was administered 5.1 +/- 0.03 (median 5) drug prescriptions. The incidence of probable or definite adverse drug reactions was 5.8% (532/9,148). In univariate analysis, the incidence of adverse drug reactions increased from 3.3% at under age 50 to 6.5% at age 70-79 and decreased over age 80 (5.8%). In multivariate logistic regression, taking more than four drugs (OR = 2.94, CI = 2.38-3.62), staying in hospital more than 14 days (OR = 2.82, CI = 2.26-3.52), having more than 4 active medical problems (OR = 1.78, CI = 1.29-2.45), staying in a medical ward instead of geriatric ward (OR = 1.33, CI = 1.09-1.63), and drinking alcohol (OR = 1.28, CI = 1.03-1.58) were positively correlated with adverse drug reactions occurrence (P less than 0.05). Age, gender, and smoking cigarettes were not significant predictors of adverse drug reactions. CONCLUSION: Age is not an independent risk factor of adverse drug reactions, and good geriatric care can reduce the incidence of adverse drug reactions. PMID- 1753049 TI - The home care practice and attitudes of Minnesota family physicians. AB - OBJECTIVE: Assess home care practice and attitudes of Minnesota family physicians (FPs). DESIGN: Mailed survey. SETTING: State of Minnesota. PARTICIPANTS: Members of the Minnesota Academy of Family Physicians, 80% of the FPs practicing in the state. INTERVENTION: A 55-item mailed, self-complete questionnaire regarding general practice and personal physician characteristics (18 questions), specific questions regarding geriatric and home care practice and related attitudes (37 questions); up to four reminder or follow-up surveys were sent. MAIN OUTCOME MEASURES: Descriptive summary of FP home care practice and attitudes. RESULTS: Eighty percent of surveys were completed, 76% of responding physicians made at least one home visit in the previous year, and 92% of home visits were to geriatric patients. Discriminant function analysis identified six significant (P less than 0.001) variables that explained 52% of the variance (r2 = 0.52, Wilks Lambda = 0.48) in home visiting behavior between frequent home visiting FPs (greater than 24 visits/year) and non-visiting FPs. FPs most likely to do home visiting were older and tended to have small group or solo practices in rural settings. CONCLUSION: The survey documented continued decline (from previously published surveys) of physician home visiting behavior and widespread dissatisfaction with reimbursement. However, attitudes regarding home care provided by other professionals were highly positive. PMID- 1753050 TI - Methicillin-resistant Staphylococcus aureus in Minnesota nursing homes. AB - OBJECTIVE: To assess the experience of Minnesota nursing homes with methicillin resistant Staphylococcus aureus (MRSA) and the policies and procedures used for its control. DESIGN: A 12-question survey, with primarily categorical responses, was mailed to the Directors of Nursing of all Minnesota long-term-care facilities. A follow-up mailing was sent to non-responders 5 weeks later. The mailing included a cover letter, a description of the study and its purposes, and a stamped return envelope. Four weeks after the second mailing, all non responding institutions were contacted by telephone and invited to participated by mail or by completing the survey by telephone. SETTING: All long-term-care facilities in Minnesota licensed for skilled and intermediate care. PARTICIPANTS: The survey was directed to the Directors of Nursing of the long-term-care facilities with the request that, if another individual was better able to complete it, the survey be forwarded to them. RESULTS: Completed responses were obtained from 88% (395/445) of all long-term-care facilities in Minnesota. Forty eight institutions (12%) had residents colonized or infected with MRSA. Only four (8%) of these facilities stated that MRSA was a problem; however, 33 (69%) of facilities with MRSA had sought outside help or consultation from a variety of sources for its control. Few facilities (7%) had cultured residents specifically for MRSA. Policies regarding the admission of colonized or infected persons were reported by 14% and 21% of facilities, respectively, and over 40% of these policies stated that persons with MRSA would not be accepted. Policies regarding the care of MRSA-colonized or -infected persons were not uniform. Both metropolitan and non-metropolitan facilities had residents with MRSA. CONCLUSIONS: Our results suggest that MRSA in long-term-care facilities may be a widespread and underrecognized problem. There is a need to develop uniform policies for the control of MRSA in nursing homes. These policies should consider the sources and objectives of long-term-care facilities. PMID- 1753051 TI - The use of estrogen to decrease aggressive physical behavior in elderly men with dementia. PMID- 1753052 TI - Breast cancer of the older woman: an annotated review. PMID- 1753053 TI - Refusal of tube feeding as seen from a patient advocacy organization: a comparison with landmark court cases. AB - OBJECTIVE: To determine how closely high court decisions regarding tube feeding are a reflection of the situations that occur in the general population. DESIGN: A retrospective review was conducted of memos recording inquiries made to the Society for the Right to Die (SRD), a patient advocacy organization. Characteristics of clients were compared to characteristics of individuals considered in landmark "right-to-die tube feeding cases during the same period of time. RESULTS: Information from 116 memos of inquiries made from 1985 through mid 1990 was compared to 20 court cases, and significant differences were identified. The average age of the SRD clients was 77.6 (+/- 18.4) years compared to 55.1 (+/ 22.8) years for the court cases (P less than 0.001). Of the clients, 79% were 70 years of age or older and 28% were 90 or older; in contrast, 7 (35%) of subjects in the court cases were 70 years of age or older, and none was over 90 (P less than 0.001). In addition, whereas 14 (70%) of the court cases dealt with individuals in a persistent vegetative state, only 17 (15%) of SRD clients carried that diagnosis (P less than 0.001), with the remainder suffering from dementia, various stages of coma, or a variety of other debilitating disorders. The sex distribution, year of inquiry or year of court decision, and geographic distribution were similar. Some states were overrepresented in both groups. CONCLUSION: High court cases may inadequately reflect the majority of situations that arise on a day-to-day basis. Elderly individuals, in particular those who are not in a persistent vegetative state, are significantly underrepresented. PMID- 1753054 TI - The financial impact of a nursing home practice on an academic medical center. AB - This study reports the economic contributions of nursing home practice to an academic department of family practice as well as the fiscal impact of referrals from nursing home practice on an academic medical center. Payment to primary physician faculty for nursing home service did not fully compensate for faculty effort. Nevertheless, these services did result in significant revenues to consulting physicians and the University Hospital. In aggregate, an average nursing home visit was associated with $33 in charges for the visit by the primary physician, $15 for additional primary care services in the clinic and hospital, $72 for services by consulting physicians, and $307 in charges by the University Hospital. The average nursing home patient provided $3,744 in charges and $2,403 in income to the academic medical center per year, with $1,813 going to the hospital and $331 to consulting physicians. Even though primary care is not well reimbursed, a relatively small number of patients have the capacity to create substantial income for consulting physicians and the hospital. The study does not address whether these nursing home referrals to the hospital utilized disproportionately high hospital resources. PMID- 1753055 TI - A multidisciplinary approach in the evaluation of demented drivers referred to geriatric assessment centers. PMID- 1753056 TI - Dementia and driving. PMID- 1753057 TI - Why do physicians fail to recognize and treat malnutrition in older persons? PMID- 1753058 TI - Depression in Alzheimer's disease significantly improved under treatment with mianserine. PMID- 1753059 TI - Uncertain diagnosis of an uncertain entity? PMID- 1753060 TI - DNR orders at nursing homes. PMID- 1753061 TI - The myth of the myth of senility. PMID- 1753062 TI - Vagal influences on gastric acid secretion in response to gastric distension in the ferret. AB - The role of the vagus nerve in the stimulation of gastric acid secretion was investigated by comparing the acid output in response to gastric distension during augmented secretion mediated by electrical vagal stimulation and pentagastrin. Under control conditions distension increased acid output from 29.8 +/- 3 mumol/10 min to 59.9 +/- 5.5 mumol/10 min (P less than 0.0001). Bilateral cervical vagotomy significantly reduced both basal acid secretion and the response to distension although the increase during distension was still significant. Electrical vagal stimulation augmented basal acid output and the response to distension, and at 1 Hz both parameters were not different from that before vagotomy. However, the sensitivity of the response to distension was unchanged by vagal stimulation. Pentagastrin infusion augmented basal acid secretion and the response to distension in a similar manner to vagal stimulation. We conclude that the vagus nerves potentiate the gastric acid secretory response to distension not by facilitating enteric reflexes but by an action at the level of the parietal cell. PMID- 1753063 TI - The pathway of parasympathetic nerve fibers to cerebral vessels from the otic ganglion in the rat. AB - It has previously been shown that the otic ganglion contributes to the innervation of pial arteries in the rat with parasympathetic fibers, but the exact pathway from the ganglion to the vessels has been unknown. Further, the precise course of the lesser superficial petrosal nerve in the rat has not been described. In this research we show, by combining retrograde neuronal tracer technique and immunohistochemical demonstration of transmitters, that the fibers leave the ganglion in the lesser superficial petrosal nerve, running on the anterior and medial inner surface of the tympanic bulla to reach the greater superficial petrosal nerve, and deviate via the deep petrosal nerve to the wall of the internal carotid artery. Various other nerves were excluded as possible pathways. PMID- 1753064 TI - Changes in sympathetic and endothelium-mediated responses in the rabbit central ear artery after acrylamide treatment. AB - The effect of acrylamide intoxication on the innervation and local control of the rabbit central ear artery was investigated. There was no difference in the noradrenaline, neuropeptide Y and calcitonin gene-related peptide tissue content between control and experimental animals. There was, however, a slight reduction in catecholamine histofluorescence. Although the contractile efficiency of the rabbit central ear artery as measured by responses to potassium chloride was unchanged, nerve-mediated contractile responses were significantly attenuated in acrylamide-treated animals. Contractile responses induced by exogenous alpha,beta methylene ATP were markedly increased after acrylamide treatment, in contrast to contractions induced by exogenous noradrenaline which were attenuated at maximal concentrations. Modulatory effects of nerve-mediated contractile responses by neuropeptide Y were unaffected by acrylamide intoxication. It therefore appears that acrylamide intoxication damages sympathetic cotransmission, perhaps with preferential action on the purinergic component. Endothelium-dependent relaxant responses to acetylcholine and substance P were attenuated in acrylamide-treated animals, whereas relaxant responses mediated by calcitonin gene-related peptide (endothelium independent) were unaffected. The question of whether the damage to the endothelial cell action is a primary effect, or a secondary consequence of sympathetic nerve damage, is discussed. PMID- 1753065 TI - The effect of brain transection on the response to forced submergence in ducks. AB - The effect of brain transection at two levels on cardiovascular responses to forced submergence has been investigated in ducks. Compared with intact ducks, neither decerebration nor brain stem transection at the rostral mesencephalic (RM) level had any effect on development of diving bradycardia, or heart rate at the end of two-min dives. Arterial blood pressure was maintained in brain transected ducks as well as in intact ducks. Furthermore, end-dive arterial blood gases and pH were also similar in intact and brain transected ducks confirming that the oxygen sparing cardiovascular adjustments, involving a massive increase in total peripheral resistance, were unimpaired by brain transection. In this respect, ducks with RM transections tolerated four-min dives. However, the increase in post-dive VE seen in intact and decerebrated ducks was prevented by RM transection. We conclude that control of the circulatory response to diving resides in the lower brainstem, is reflexogenic in nature, and does not depend on the cognitive perception of 'fearful' stimuli. PMID- 1753066 TI - The placental transfer of calcium. PMID- 1753067 TI - The effect of selective umbilical embolization on the common umbilical artery pulsatility index and umbilical vascular resistance in fetal sheep. AB - In eight anaesthesized fetal sheep (gestational age 112-127 days; term 147 days), embolization of the umbilical placental circulation was performed in order to evaluate the response of the umbilical artery pulsatility index to an exclusive increase in umbilical vascular resistance. Measurements were performed using a 20 MHz pulsed Doppler transducer and an electromagnetic flow meter mounted on the common umbilical artery and catheters at the aortic trifurcation and in one of the umbilical veins. Umbilical vascular resistance was calculated according the Poiseuille equation as the ratio of aortic to umbilical venous pressure gradient and umbilical blood flow. Microspheres were administered at 15-min intervals through a catheter in one of the cotyledonary arteries, until fetal heart rate had decreased beneath 100 beats/min or had become arrhythmic. The period of examination per fetus varied between 60 and 120 min, after which cardiac decompensation occurred. During this period, umbilical perfusion pressure increased from 20.3 +/- 4.9 to 28.1 +/- 4.7 mmHg (SD; P less than 0.01), umbilical blood flow (ml/min) decreased from 342 +/- 127 to 115 +/- 99 mmHg (SD; P less than 0.01), umbilical vascular resistance increased from 0.065 +/- 0.022 to 0.342 +/- 0.150 mmHg.min/ml (P less than 0.01) and common umbilical artery pulsatility index increased from 0.97 +/- 0.23 to 4.03 +/- 1.69 (P less than 0.01). Fetal heart rate did not change significantly (168 +/- 33 prior to cardiac decompensation versus 178 +/- 19 beats/min at baseline condition). The linear correlation between common umbilical artery pulsatility index and umbilical vascular resistance varied between 0.83 and 0.99 and the average correlation was 0.93 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753068 TI - Respiratory and non-respiratory thoracic movements in the fetal pig. AB - The aim of this study was to characterize the pre-natal activity of the respiratory muscles in a non-ruminant, the pig. Tracheal pressure was recorded from 11 unanaesthetized fetal pigs in utero during late gestation in 9 sows. Two types of inspiratory effort occurred episodically in each fetus during each recording period. Episodes of breathing movements lasted 8.6 +/- 1.1 min and their overall incidence was 41.1 +/- 3.4% of recording time. The mean amplitude of the respiratory efforts was 7.6 +/- 1.1 mmHg and the mean inspiratory time was 0.8 +/- 0.1 s. Episodes of non-respiratory inspiratory efforts, considered to be fetal hiccups, lasted 5.6 +/- 0.8 min. Individual hiccups had a duration of 150 200 msec, a mean amplitude of 41.4 +/- 2.4 mmHg and a mean frequency, during episodes, of 21.9 +/- 2.0 min-1. In contrast to fetal breathing movements, hiccups appeared to be stereotyped events. It is concluded that, in common with other ruminant and non-ruminant species, two types of inspiratory effort occur in the fetal pig. Fetal hiccups, which have been observed in non-ruminant species, may be analogous to deep inspiratory efforts in the sheep fetus. The stimulus for, and function of, fetal hiccupping remain to be determined. PMID- 1753069 TI - Behavioral state transition and local cerebral blood flow in fetal sheep. AB - Local cerebral blood flow in four near term fetal sheep was evaluated continuously before and after natural alternations in fetal behavioral state. Measurements were made in fetuses several days following an aseptic surgery to place electrodes for behavioral state recordings as well as heated and reference thermojunctions in cortical and subcortical tissue. These thermojunctions were used to qualitatively assess local cerebral blood flow. The time of transition between rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) was based on visual inspection of strip chart recordings of electrocortical, electroocular, and neck electromyographic activity and application of published criteria for their assessment. To confirm that transition had occurred, the amplitude of the spectrum of the electrocorticogram in one-third octave bands centered around 1 Hz and 20 Hz was measured before and after the transition point. Mean cerebral blood flow rose significantly by 24 s (P less than 0.05) after the transition from NREMS to REMS and fell by 12 s after the transition from REMS to NREMS (P less than 0.05). PMID- 1753070 TI - Urogastrone-epidermal growth factor and aspects of sexual maturation in female rats as a function of age at treatment. AB - The effect of epidermal growth factor (EGF) on sexual maturation of female rats was studied. A within-litter experimental design was employed, so that in each litter each female received four daily injections of EGF (E, 500 ng/g body weight s.c.) or vehicle (V), at one of three ages: days 0-3 (E1, V1), days 8-11 (E2, V2), days 16-19 (E3, V3). Body weight, pinna detachment, incisor eruption, eye opening, auditory startle, visual placing, vaginal opening and first cytological oestrus were assessed. Neonatal treatment with EGF (E1) delayed pinna detachment and the appearance of the auditory startle, but accelerated eye opening. Also, E1, but not E2 and E3, resulted in lower body weight at weaning. Treatment E3 advanced sexual maturation, as indicated by vaginal opening and first cytological oestrus, by 5-6 days. E1 and E2 had no such effect. Hence the sensitive period for the effect of EGF on female rat sexual maturation is later than that for effects on other developmental characteristics and body weight. In a second experiment, ovary and uterus weights were found not to differ between E3 and V3 females killed on the day of vaginal opening of the E3 rats, suggesting that the effect of EGF may be specifically on the perineal epithelium and not on sexual maturation generally. PMID- 1753071 TI - Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery. AB - We examined the effect of graded reduction in uterine blood flow on distribution of cardiac output and oxygen delivery to fetal organs and venous blood flow patterns in 9 fetal sheep using the radionuclide-labeled microsphere technique. We reduced uterine blood flow in two steps, decreasing fetal oxygen delivery to 70% and 50% of normal, and compared the results with those from a similar study from our laboratory on graded umbilical cord compression. With 50% reduction in fetal oxygen delivery, blood flow and the fraction of the cardiac output distributed to the brain, heart, and adrenal gland increased and that to the lungs, carcass, skin, and scalp decreased. Oxygen delivery to the brain and myocardium was maintained, while that to the adrenal doubled, and that to the brain stem increased transiently. The decrease in oxygen delivery to both carcass and lower body segment correlated linearly with oxygen consumption (P less than 0.001). The proportion of umbilical venous blood passing through the ductus venosus increased from 44.6% to 53% (P less than 0.05). The preferential distribution of ductus venosus blood flow through the foramen ovale to the heart and brain increased, but that to the upper carcass decreased so that ductus venosus-derived blood flow to the upper body did not change. Hence, the oxygen delivered to the brain from the ductus venosus was maintained, and that to the heart increased 54% even though ductus venosus-derived oxygen delivery to the upper body fell 34%. Abdominal inferior vena caval blood flow and its contribution to cardiac output decreased, but the proportion of the abdominal inferior vena caval blood distributed through the foramen ovale also increased from 23.0 to 30.9%. However, the actual amount of inferior vena caval blood passing through the foramen ovale did not change. There was a 70% fall in oxygen delivery to the upper body segment from the inferior vena cava. A greater portion of superior vena caval blood was also shunted through the foramen ovale to the upper body, but the actual amounts of blood and oxygen delivered to the upper body from this source were small. Thus, graded reduction of uterine blood flow causes a redistribution of fetal oxygen delivery and of venous flow patterns, which is clearly different from that observed previously during graded umbilical cord occlusion. PMID- 1753072 TI - The interaction of behavioural state, heart rate and resistance index in the human fetus. AB - The association and possible interactions of fetal behavioural state, fetal heart rate and vascular resistance was studied in 23 healthy pregnant women between 36 and 40 weeks' gestation. Doppler flow velocity waveforms were obtained from fetal cerebral (anterior cerebral, internal carotid and basilar), descending aorta and umbilical arteries during fetal behavioural state 1F and repeated during 2F. The Resistance Index (RI) was used as a measure of vascular resistance. Decreased vascular resistance was observed in all vessels except the umbilical artery during fetal behavioural state 2F compared to 1F (P less than 0.001). A significant interaction was observed between fetal heart rate and fetal behavioural state on the RI of the vessels studied, with a greater negative slope for RI plotted against fetal heart rate in fetal behavioural state 2F (-0.00139) compared to 1F (0.00005) (P less than 0.001). We conclude that the transition from fetal behavioural state 1F to 2F is associated with a significant reduction in cerebral and systemic vascular resistance, with no apparent change in placental resistance. Furthermore, fetal behavioural state and fetal heart rate interact, demonstrating a stronger association of fetal heart rate and RI in fetal behavioural state 2F in keeping with an increase in baroreflex sensitivity at this time. PMID- 1753073 TI - Arterial oxygen saturation and breathing movements during the first year of life. AB - Sixteen healthy term infants underwent 12 hour tape recordings of arterial oxygen saturation (SaO2)(Nellcor N100 in beat to beat mode) and breathing movements at around 6 weeks, 3 and 6 months of age. Six of these infants had an additional recording at around their first birthday. Recordings were analysed throughout for pauses in breathing movements of greater than or equal to 4 s (apnoeic pauses), episodes in which SaO2 fell to 80% (desaturations), and (only during regular breathing) baseline SaO2. In the 16 infants studied at 6 weeks, 3 and 6 months, the median frequency of both apnoeic pauses (5.6, 5.7, and 6.1/h, respectively) and desaturations (0.7, 0.4 and 0.5/h, respectively) showed little change. The majority of desaturations followed an apnoeic pause (median 73.2, 86.2 and 93.8% of desaturations). The median proportion of apnoeic pauses followed by a desaturation did not change significantly (9.0, 7.5 and 9.1%), despite an increase in the proportion of apnoeic pauses of greater than or equal to 8 s in duration from 2.0% at 6 weeks to 5.3% at 3 months (P less than 0.01). Baseline SaO2 was 97.3% or higher in all recordings. Median baseline SaO2 increased from 99.6 to 99.9% between 6 weeks and 3 months (P less than 0.02) and remained unchanged thereafter. In the subgroup of infants studied also at one year of age, again no significant differences were found with increasing age in the frequency of either apnoeic pauses or desaturations. The data show that in healthy subjects no major changes occur between 6 weeks and 1 year of life in apnoeic pause frequency or arterial oxygenation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753074 TI - Changes in fetal and maternal plasma protein concentration and colloid osmotic pressure with gestation. AB - In pregnant ewes, plasma protein levels over the gestation age range of 58-141 days fell progressively (r = -0.332, P less than 0.05, n = 36) but colloid osmotic pressure (COP, mmHg) did not change significantly. In fetal sheep carried by these ewes, plasma protein levels increased with age (r = 0.85, P less than 0.00001, n = 32). COP also rose (r = 0.8, P less than 0.00001, n = 23). Since maternal COP did not change and fetal COP increased, the net transplacental COP gradient between mother and fetus decreased with increasing age (r = -0.589, P less than 0.004, n = 22). Fetal plasma protein levels can be used to calculate fetal COP while maternal plasma protein levels cannot be used to calculate maternal COP. PMID- 1753075 TI - Growth and metabolism of the placenta after unilateral fetectomy in twin pregnant ewes. AB - Twin-pregnant ewes underwent unilateral fetectomy (Fetx) at 50 days of gestation and were studied at 136 days. Aspects of conceptus growth and placental cellularity and metabolism in vitro were compared to those of unoperated control groups of twin-pregnant or single-pregnant ewes. Mean fetal weight in Fetx ewes tended to be greater than that of twin-pregnant ewes and was similar to that of single-pregnant ewes. Mean placental wet and dry weights were intermediate between those for naturally single- and twin-pregnant animals. Fetectomy caused a significant increase in placental protein:DNA ratio but an unchanged DNA concentration, apparently due to cellular hypertrophy in the placenta of the remaining fetus. Weight-specific rate of oxygen consumption (VO2) of fetal placental tissue in twin-pregnant ewes was higher than in Fetx or singles while maternal placental VO2 in twins tended to be lower than in either of the other two groups. These results highlight the plasticity of placental metabolism and growth, perhaps in response to altered trophic signals from the fetus. Unilateral fetectomy should prove useful in studies designed to identify these signals. PMID- 1753076 TI - Infected urine and prostatectomy wound infection. PMID- 1753077 TI - Antibiotic dosing. PMID- 1753078 TI - The costs of hospital infection control in a developing country. PMID- 1753079 TI - Cost improvements through the establishment of prudent infection control practices in a Brazilian general hospital, 1986-1989. AB - OBJECTIVES: To review procedures currently practiced in a Brazilian general hospital and to eliminate ineffective and inefficient practices. To measure the resulting cost improvements based on rigid hospital financing control. DESIGN: Implementation of surveillance and control programs and prevalence surveys to detect ineffective and inefficient practices. PARTICIPANTS: The study institution is a 130-bed general care facility affiliated with the Brazilian federal government. There were approximately 4,600 admissions per year during the study period (1986-1989). RESULTS: Instituting infection control measures and eliminating ineffective practices resulted in the following: an overall decrease in wound infection rates from 24.4% in 1987 to 3.45% in 1989; a 71% reduction in the global incidence of infection in the intensive care unit; a 74% reduction in the surgical prophylactic use of antibiotics; and a total savings of approximately $2 million (US dollars). CONCLUSIONS: During the period from 1986 to 1989, the infection control committee was able to decrease the overall wound infection rate from 24.4% in 1987 to 3.45% in 1989. This eliminated special health problems and improved patient care and cost-effectiveness for our hospital. PMID- 1753080 TI - Failure of bland soap handwash to prevent hand transfer of patient bacteria to urethral catheters. AB - OBJECTIVE: The study was designed to compare the efficacies of bland soap handwash and isopropyl alcohol hand rinse in preventing transfer of aerobic gram negative bacilli to urinary catheters via transient hand colonization acquired from direct patient contact. Glove juice recovery of gram-negative bacteria was considered transient colonization; catheter recovery was considered transfer colonization. DESIGN: The contact source for gram-negative bacteria was a single "high burden" groin skin carrier (greater than or equal to 10(4)/ml cup scrub fluid). Using a two-period cross-over design, 6 healthcare workers had 2 15 second contacts for each hand followed by either soap handwash or alcohol hand rinse (12 experiments with each treatment). Between 4 to 5 minutes after contact, each hand manipulated a catheter; the catheter was then cultured and the hand was glove juice tested. RESULTS: Soap handwash failed to prevent gram-negative bacteria transfer to the catheter in 11 of 12 (92%) experiments; alcohol hand rinse in 2 of 12 (17%) (p less than .001). Soap handwash failed to prevent transient colonization in 12 of 12 (100%) experiments; alcohol in 5 of 12 (42%) (risk ratio 2.4, 95% confidence interval 1.2-4.7). Single gram-negative bacteria species carried at source levels greater than or equal to 5.5 x 10(3)/ml (heavy contamination) established transient colonization in 23 of 30 (77%) exposures following soap handwash; single gram-negative bacteria species carried at levels less than or equal to 3.5 x 10(3)/ml established colonization in 1 of 22 (5%) similar exposures (p less than .001). CONCLUSIONS: Bland soap handwash was generally ineffective in preventing hand transfer of gram-negative bacteria to catheters following brief contact with a heavy-contamination patient source; alcohol hand rinse was generally effective. PMID- 1753081 TI - Measles immunity among community hospital employees. AB - OBJECTIVE: To define measles immunity rates among employees at 2 hospitals during a community outbreak in 1990. DESIGN: Cohort survey using enzyme-linked immunosorbent assay (ELISA) and questionnaire. SETTING: Two community hospitals. PARTICIPANTS: Seventy-six percent of 2,060 employees. RESULTS: Seven percent (115/1566) of participants lacked ELISA-defined measles immunity. Among employees whose ages were known, 14% (64/467) of those born after 1956 and 5% (50/1086) of those born before 1957 lacked serologic evidence of immunity. Fifty-eight percent of the susceptible persons had substantial patient contact. With ELISA results as the reference for immunity, the predictive value of an undocumented positive history of measles disease or vaccination was 95%; the predictive value of a negative history of both was 52%. Measles developed in 7 employees. CONCLUSIONS: A substantial number of hospital employees lacked ELISA-defined measles immunity, including many who had patient contact or who had been born before 1957. Undocumented disease and vaccination histories were not adequate predictors of serologic status. This study supports the recommendations and suggestions of the Immunization Practices Advisory Committee that hospitals should require documented evidence of measles immunity from employees who have patient contact. PMID- 1753082 TI - Evaluation of the epidemiology of hepatitis B virus cross-infection in a maternity hospital. AB - OBJECTIVE: To determine the hepatitis B infection risk in a university hospital of obstetrics and gynecology. SETTING: The University Hospital of Obstetrics and Gynecology, The University of Sarajevo, Yugoslavia. DESIGN: Staff members were divided into three groups: 73 doctors, 184 medical technicians working in delivery rooms, and 55 medical technicians working with postnatal care. The patients were 63 women, aged 17 to 39 years (mean = 26.11 years), pregnant for the first time and in the first stage of labor. Participants all had a negative history of hepatitis B and no known contact with the hepatitis B virus. RESULTS: The incidence of hepatitis B infections among physicians, technicians, and postnatal care technicians was 1.36%, 3.8%, and 3.6%, respectively. The incidence among patients was 4.76%. The daily infection risk varied between 1% and 17% of all deliveries. CONCLUSIONS: The risks of transmission of the hepatitis B virus to hospital workers in this setting is indeed high enough to make a case for hepatitis B vaccination in susceptible staff members. Even if vaccination of staff members is carried out, hygienic measures to prevent the transmission of bloodborne infection between patients and from patients to staff are of the utmost importance. PMID- 1753083 TI - Infection control violations. PMID- 1753084 TI - Malassezia furfur infections. PMID- 1753085 TI - Medical waste: a minimal hazard. AB - Medical waste is a subset of municipal waste, and regulated medical waste comprises less than 1% of the total municipal waste volume in the United States. As part of the overall waste stream, medical waste does contribute in a relative way to the aesthetic damage of the environment. Likewise, some small portion of the total release of hazardous chemicals and radioactive materials is derived from medical wastes. These comments can be made about any generated waste, regulated or unregulated. Healthcare professionals, including infection control personnel, microbiologists, public health officials, and others, have unsuccessfully argued that there is no evidence that past methods of treatment and disposal of regulated medical waste constitute any public health hazard. Historically, discovery of environmental contamination by toxic chemical disposal has followed assurances that the material was being disposed of in a safe manner. Therefore, a cynical public and its elected officials have demanded proof that the treatment and disposal of medical waste (i.e., infectious waste) do not constitute a public health hazard. Existent studies on municipal waste provide that proof. In order to argue that the results of these municipal waste studies are demonstrative of the minimal potential infectious environmental impact and lack of public health hazard associated with medical waste, we must accept the following: that the pathogens are the same whether they come from the hospital or the community, and that the municipal waste studied contained waste materials we now define as regulated medical waste.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753086 TI - The nonexistent problem. AB - Effective assessment of problems is essential for the infection control practitioner to function optimally. Today's infection control practitioner not only learns problem solving on the job but is trained in both individual and participatory problem solving techniques. Correct response to a potential problem requires careful investigation and identification of causal relationships. Most literature, however, is directed at solving problems that exist. The phenomenon of nonexistent problems exists when the presented problem is not real but exists only in the perception of the presenter. In some cases, the nonexistent problem may partially represent a real problem, but the relationship may not be readily apparent. Time spent by infection control practitioners responding to nonexistent problems is significant. Without the ability to distinguish between nonexistent and existent problems, needless and ineffective actions may be taken. It is essential that the infection control practitioner understand both the dynamics resulting from the presentation of nonexistent problems and their characteristics. PMID- 1753087 TI - A recombinant C-terminal fragment of staphylococcal enterotoxin A binds to human MHC class II products but does not activate T cells. AB - Binding of staphylococcal enterotoxin A (SEA) to MHC class II encoded proteins is a prerequisite for its subsequent activation of a large fraction of T lymphocytes through interaction with variable segments of the TCR-beta chain. We cloned SEA in Escherichia coli and produced four recombinant fragments covering both the N- and C-terminal regions. These fragments were used to analyze the interaction between SEA and the human MHC class II products. A C-terminal fragment of SEA, representing amino acids 107-233 bound to HLA-DR and HLA-DP but did not activate T cells. The three other fragments (amino acids 1-125, 1-179 and 126-233) neither bound to MHC class II Ag nor activated T cells. SEA apparently bind to HLA-DR and HLA-DP through its C-terminal part, whereas T cell activation is dependent on additional parts of the protein. PMID- 1753088 TI - The preference for switching to IgA expression by Peyer's patch germinal center B cells is likely due to the intrinsic influence of their microenvironment. AB - This study was aimed at determining whether the chronically activated physiologic state of Peyer's patch (PP) tissue is primarily responsible for the IgA isotype preference expressed by PP germinal centers (GC) and memory B cells. We have used reovirus type 1/Lang to stimulate acute, de novo GC reactions in lymph nodes (LN) or PP to test the possibility that the surface (s)IgA component of enteric responses is peculiar to the local gut microenvironment whether or not PP are in a state of chronic activation. GC were raised in PP of germ-free mice by oral administration of virus and in lymph nodes (LN) of conventionally reared mice by local parenteral infection. Transient GC reactions were found to develop with similar time courses in both PP and LN after both primary and secondary local infections with reovirus. sIgA+ B cells, which were the major non-sIgM+/sIgD+ population found to arise in GC of PP, were not found in the LN. In LN, sIgG1+ B cells comprised the predominant non-IgM/IgD bearing population that arise after local infection. Lymphoid fragment cultures of PP initiated in vitro as early as 5 days after in vivo infection contained detectable secreted reovirus-specific IgA, whereas IgG1 but no IgA was found in LN cultures. Northern blot analysis to detect C alpha and C gamma 1 germline transcripts further substantiated a site related bias in the expression of non-IgM/IgD isotypes that was manifest within a few days after infection. In summation, these observations taken together suggest that the preference for generating sIgA+ B cells in PP may be the result of intrinsic features of their gut microenvironment. PMID- 1753089 TI - Natural antibodies can inhibit bone marrow engraftment in the rat----mouse species combination. AB - Specific tolerance can be induced in animals by transplanting hemopoietic cells across concordant species barriers. Despite the fact that the rat-mouse species combination is considered concordant, we have recently demonstrated that normal murine serum contains natural antibodies (nAb), predominantly of the IgM and IgG3 subclasses, with markedly greater binding to rat bone marrow cells (BMC) than to rat splenocytes or thymocytes. Since much greater numbers of rat BMC than of allogeneic murine BMC are required to achieve engraftment in mice, we considered the possibility that these nAbs might be responsible, and that the increased numbers of BMC might be required to absorb these nAb. To evaluate the effect of these nAb on engraftment of rat BMC in mice, we have now performed adoptive transfer studies using T and B cell-deficient severe combined immunodeficiency disease (SCID) mice as recipients. Administration of as few as 5 x 10(5) T cell depleted rat BMC led to induction of stable xenochimerism in SCID mice conditioned with 4-Gy whole body irradiation. Rat T cells developed after a delay of several weeks, and conferred the ability to reject non-donor-type rat skin grafts, whereas donor-type grafts were accepted. Adoptive transfer of 4 ml of normal BALB/c serum led to a marked reduction in the level of rat chimerism in SCID recipients of 2 x 10(6) F344 BMC. The ability of sera to inhibit engraftment of rat BMC correlated with their cytotoxic nAb content, and the inhibitory effect of highly cytotoxic sera could be overcome by administration of large numbers of rat BMC. Thus, normal mouse serum has a limited ability to hinder engraftment of rat BMC, and this degree of resistance can be overcome by adsorption when large numbers of BMC are administered. Eliminating nAb from serum may be more difficult in discordant species combinations in recipients with functional B cells, but may likewise permit the use of BMT as a means of inducing transplantation tolerance. PMID- 1753090 TI - Hemorrhage induces enhanced Kupffer cell cytotoxicity while decreasing peritoneal or splenic macrophage capacity. Involvement of cell-associated tumor necrosis factor and reactive nitrogen. AB - Studies indicate that simple hemorrhage produces a profound depression of cell mediated immunity, thereby contributing to an enhanced susceptibility to septic challenge in the host. However, it remains unknown whether or not the macrophages' cytotoxic capacity is altered after hemorrhage. To study this, C3H/HeN mice were bled to and maintained at a blood pressure of 35 mm Hg for 60 min, and adequately resuscitated. Mice were then killed at 2 or 24 h after hemorrhage to obtain peritoneal macrophage, splenic macrophage, and Kupffer cells. Cytotoxicity was assessed by determining the capacity of these macrophages to lyse [3H]TdR labeled WEHI-164 clone 13 or P815 tumor target cells (WEHI-164, sensitive to both soluble and cell-associated TNF vs P815 cells, insensitive to soluble TNF). Peritoneal and splenic macrophages from hemorrhaged animals exhibited a significantly reduced cytotoxic capacity, whereas Kupffer cells' ability to kill the target cells was enhanced. Similarly, the Kupffer cells' capacity to release TNF and IL-1, as well as express cell-associated forms of this cytokine are significantly enhanced on macrophages isolated 2 h after hemorrhage, whereas peritoneal macrophages are not. Furthermore, antibodies directed at mouse TNF but not against murine IL-1 alpha or murine IL-6 were able to oblate the enhanced target cell lysis of unfixed, as well as paraformaldehyde fixed (metabolically inactive) Kupffer cells. Studies using inhibitors (GN monomethyl-arginine, superoxide dismutase, catalase, and ibuprofen) of other TNF inducible mechanisms of target cell killing indicated that only the inhibition of the release of reactive nitrogen consistently depressed the cytotoxic capacity of Kupffer cells from hemorrhaged mice. Thus, the increased Kupffer cell cytotoxicity from hemorrhaged mice is most likely mediated through the expression of cell-associated TNF and the release of reactive nitrogen. PMID- 1753091 TI - Induction of in vivo hyporesponsiveness to contact allergens by hapten-modified Ia+ keratinocytes. AB - Because our previous in vitro studies of hapten-modified Ia+ keratinocytes (KC) indicated that these cells induced anergy in Ag-specific Th1 cells, we assayed such cells for their ability to induce unresponsiveness in an in vivo animal model system of delayed type hypersensitivity (allergic contact dermatitis). Naive animals that were treated with i.p. injections of FITC-modified Ia+ cultured Langerhans cells (cLC) developed allergic contact dermatitis to subsequent hapten challenge; whereas, animals treated with similar doses of FITC Ia+ KC failed to become sensitized to epicutaneous application of FITC, as evidenced by absent ear swelling responses to a FITC challenge. Those animals that were first treated with intraperitoneal injections of hapten modified Ia+ KC could not be sensitized when they were subsequently exposed to sensitizing doses of FITC; whereas a similar first exposure to FITC-cultured Langerhans cells did not interfere with epicutaneous sensitization. This hyporesponsiveness to sensitization was hapten specific, as FITC-Ia+ KC-treated animals were hyporesponsive only to FITC but not to the irrelevant hapten, TNCB. Additionally, Ia- KC failed to induce unresponsiveness. Additional studies indicate that the hyporesponsiveness was not passively transferrable with splenocytes and was not related to the I-J MHC locus. In contrast to our in vitro studies, the unresponsiveness induced by hapten-modified Ia+ KC in vivo was transient in nature. These data indicate that hapten-modified Ia+ KC function in vivo as nonstimulatory accessory cells, by generating down-regulatory signals that can interfere with the induction of contact hypersensitivity. PMID- 1753092 TI - Expression and synthesis of cross-reactive idiotypic antibodies by peripheral blood lymphocytes and their suppression by anti-idiotypes in patients with IgA nephropathy. AB - We have recently described that patients with IgA nephropathy present high serum levels of anti-BSA idiotypic antibodies that were well correlated with the existence of hematuria. Furthermore, these Id were found in circulating and renal deposited immune complexes. In the present work, we examined the expression of surface idiotypic determinants on PBL by flow cytometry and their in vitro production, using as reagent anti-idiotypic antibodies previously well characterized. The presence of cross-reactive Id-bearing cells was observed in 5 out of 6 patients studied, with frequencies ranging from 3 to 12% of lymphocytes. After 7 days of culture, the spontaneous synthesis of idiotypic antibodies by PBL was found elevated in 6 out of 13 (46%) patients. A major Id cell expression and production was noted in patients with active disease as defined by hematuria. The preincubation of PBL with 20 and 50 micrograms of anti-idiotypic antibodies/2 x 10(6) cells for 3 days induced a significant inhibition of cross-reactive Id production in a dose-dependent fashion, with a degree of suppression between 12 and 50% in five out of six patients studied. In the above assays, as negative controls, we used the anti-Id antibodies previously adsorbed on an Id-Sepharose column. On the whole, these results suggest that patients with IgA nephropathy present dysfunctions in the Id-Anti-Id network that could play an important role in the pathogenesis of this disease. PMID- 1753093 TI - Independent analysis of the 16/6 idiotype lupus model. A role for an environmental factor? AB - The recent description of a lupus-like disease in normal mice after injections of human mAb that bind DNA and carry the common Id 16/6 Id has excited much attention. In an effort to reproduce this model we have performed two experiments using eight human mAb three of which bear the 16/6 Id. Despite using an injection protocol very similar to that of the original authors and waiting for up to 1 yr we were unable to detect any autoantibodies or any evidence of renal disease. We suspect that our failure to reproduce the model may be due to differences in either or both the batches of CFA used, or in the animal house environments. It supports the view that a mosaic of effects is required to induce clinical expression of an autoimmune disease. PMID- 1753094 TI - Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo. AB - The adhesion receptors, LFA-1 and VLA-4, on lymphocytes mediate lymphocyte adherence to cytokine-activated endothelial cells (EC) in vitro. Based on our previous data, which suggested that the mAb TA-2 reacted with rat VLA-4, the effect of TA-2 on lymphocyte migration out of the blood was examined. Small peritoneal exudate lymphocytes (sPEL) preferentially migrate to cutaneous inflammatory reactions, whereas lymphocytes from peripheral lymph nodes (PLN) migrate poorly to inflammatory sites but home avidly to PLN. Treatment of sPEL with TA-2 inhibited sPEL migration to DTH, LPS, poly I:C, IFN-gamma, IFN alpha/beta, and TNF-alpha by 35 to 65% and their accumulation in PLN by 50%. The homing of PLN lymphocytes to PLN was not inhibited by TA-2. Spleen T cell migration to cutaneous inflammatory sites was inhibited but homing to PLN was not affected. Systemic treatment with TA-2 inhibited sPEL migration to inflamed or cytokine-injected skin by up to 70%. Similarly, TA-2 strongly inhibited the migration of Ag-stimulated PLN lymphoblasts to skin and to PLN. The migration of lymphocytes from all sources, including the peritoneum, spleen, PLN, mesenteric nodes, and Peyer's patches, to mesenteric lymph nodes and Peyer's patches was inhibited by 80% and 95%, respectively. In conclusion, our results suggest that VLA-4 and possibly other alpha 4 integrins mediate the migration of the inflammation-seeking sPEL and Ag-activated lymphoblasts to cutaneous inflammatory sites and lymph nodes but do not affect the homing of PLN lymphocytes to PLN. These integrins also appear to be necessary for the migration of all types of lymphocytes to Peyer's patches and mesenteric lymph nodes. PMID- 1753095 TI - Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. AB - The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process. PMID- 1753096 TI - In vitro induction of a Haemophilus influenzae type b polysaccharide-specific antibody response in human peripheral blood lymphocytes of individuals recently vaccinated with an oligosaccharide-protein conjugate. AB - In this paper an in vitro culture system for the induction of an antibody response to the Haemophilus influenzae type b polysaccharide (PRP) is described. Anti-PRP IgM and IgG antibody-secreting cells (ASC) and anti-diphtheria toxoid (DT) IgG ASC were detected in cultures of blood B and T cells derived from donors 4 to 6 wk after immunization with Haemophilus influenzae type b oligosaccharide mutant diphtheria toxin (CRM197) conjugate (HbOC) and required in vitro restimulation with HbOC. When lymphocytes from HbOC-vaccinated donors were stimulated with PRP, anti-PRP IgM and IgG ASC could be detected in 50% offGe cases. Lymphocytes from PRP-vaccinated donors or non-vaccinated donors consistently failed to generate anti-PRP antibodies after in vitro stimulation with HbOC. Optimal in vitro responses were observed at concentrations of 0.06 to 0.6 micrograms/ml of Ag. At higher doses of Ag (6 micrograms/ml) anti-PRP and anti-DT antibody responses were suppressed. The in vitro generation of anti-PRP and anti-DT ASC, as detected by a spot-forming cell assay was shown to be T cell dependent, Ag dependent, and Ag specific. This culture system provides a model for the study of human B cell activation and immunoregulation by polysaccharide protein conjugates and polysaccharides. PMID- 1753097 TI - Cell cycle analysis and DNA aneuploidy in autoimmune mice homozygous for the lpr and gld mutations. AB - Homozygosity for either of the mutations lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) in mice results in lymphoproliferation and autoimmune disease. To investigate the site and time of excessive lymphocyte proliferation in these mice, cell nuclei of normal and mutant mice of various ages were stained with propidium iodide and DNA profiles were analyzed by flow cytometry. Two major results were obtained. First, DNA aneuploidy was observed in the lymph nodes and spleen of these autoimmune mice and the cells involved in DNA aneuploidy were predominantly of a CD4-CD8- Thy-1- surface phenotype. Second, although DNA aneuploidy became apparent in mutant mice at 2 mo of age, the numbers of cycling cells were only minimally increased over control levels at all ages tested. Thus, the massive cellular accumulation in the lymph nodes of lpr and gld mice does not seem ascribable solely to excess cell proliferation in these tissues. Moreover, a previously unrecognized cell compartment (CD4-CD8-Thy 1-) characterized by apparent DNA aneuploidy appears in the same tissues and at the same times that the predominant "double negative" (CD4-CD8-Thy-1+) T cell subset accumulates. PMID- 1753098 TI - Immunologic control of C3 gene expression in tissue macrophages. AB - Antigenic suppression of individual complement components can be induced when newborn animals or cells in tissue culture are treated for a period of time with antibody directed against that component. The initial exposure to antibody induces a network involving regulatory lymphocytes and soluble factors. Antigenic suppression has been accomplished either in vivo or in vitro with all three members of the evolutionarily related family C3, C4, and C5. In this report we have demonstrated that antigenic suppression is mainly the result of posttranscriptional regulation. After antibody treatment is terminated, during a period in which C3 protein is undetectable by sensitive assays, C3 mRNA is often briefly increased, after which it is modestly reduced. Therefore, the major mechanisms mediating immunologic control of C3 synthesis and secretion are not directly related to steady-state levels of C3 mRNA. The initially increased levels of C3 mRNA prove that there is no simple direct quantitative relationship between C3 mRNA and C3 synthesis and secretion. The later decreases in C3 mRNA levels are not sufficient to explain the quantitatively greater decreases in C3 synthesis. Therefore, the rate determining step in immune regulation of C3 production occurs after transcription. Regulation could be mediated by altered stability of C3 mRNA in the presence of antibody, formation of a defective primary transcript, defective processing of the transcript resulting in an abnormal mRNA, or a defective C3 translational apparatus. Although regulation is multifactorial, interference with translation is most likely to predominate. PMID- 1753099 TI - Endotoxin stimulates bronchial epithelial cells to release chemotactic factors for neutrophils. A potential mechanism for neutrophil recruitment, cytotoxicity, and inhibition of proliferation in bronchial inflammation. AB - To test the effect of endotoxin on bronchial epithelial cells (BEC), BEC were isolated from bovine lungs and cultured in the presence of bacterial endotoxin. The BEC culture supernatant fluids were harvested, and neutrophil chemotactic activity (NCA) was determined with a blindwell chamber technique; cytotoxicity determined by lactate dehydrogenase release and BEC proliferation determined by Coulter counting. Endotoxin caused a dose- and time-dependent release of NCA from BEC cultures compared with media alone (82.3 +/- 8.1 vs 12.0 +/- 3.1 cells/high power field, p less than 0.001). To further characterize this activity, reverse phase HPLC analysis of release eicosanoid metabolites after [3H]arachidonic acid incorporation was performed. Endotoxin stimulated the release of the neutrophil chemoattractants, leukotriene B4 and 12-hydroxyeicosatetraenoic acids. Endotoxin also resulted in a dose and time dependent release of lactate dehydrogenase (42.9 +/- 4.2 vs 20.2 +/- 2.2 U/liter, p less than 0.001) although higher doses were required to cause cytotoxicity than to stimulate chemotaxis. Finally, endotoxin resulted in a dose dependent inhibition of BEC proliferation (176 x 10(3) +/- 16 x 10(3) vs 1,080 x 10(3) +/- 38 x 10(3) cells/ml measured at day 14, p less than 0.001). These data suggest that bacterial release of endotoxin may contribute to the pathophysiologic changes observed in bronchial inflammation by stimulating BEC to release NCA, denuding airway epithelium by causing cytotoxicity of BEC, and inhibiting epithelial repair by inhibiting BEC proliferation. PMID- 1753100 TI - Dependence of cell survival on DNA repair in human mononuclear phagocytes. AB - Mononuclear phagocytes play a central role in the pathogenesis of chronic inflammatory diseases. It is therefore important to define chemotherapeutically exploitable metabolic pathways that distinguish monocytes from other cell types. Blood monocytes do not synthesize deoxynucleotides de novo, and their transformation to macrophages occurs without cell division. Whether or not monocytes can repair DNA damage, and whether or not DNA repair is necessary for their survival, is unknown. The present experiments demonstrate that normal human monocytes, unlike neutrophils, rapidly repair DNA strand breaks induced by gamma irradiation. Monocyte extracts contain functional immunoreactive DNA polymerase alpha. DNA repair synthesis in normal monocytes is blocked by aphidicolin, an inhibitor of DNA polymerase-alpha with respect to dCTP. Aphidicolin is also directly toxic to normal monocytes, but has no effect on nondividing lymphocytes or fibroblasts. Compared to most other cell types, monocytes and macrophages have very low dCTP pools, but abundant deoxycytidine kinase activity. This suggests that dCTP derived from salvage pathways is important for DNA repair in these cells. Consistent with this notion, exogenous deoxycytidine could partially protect monocytes from aphidicolin killing. The unexpected toxicity of aphidicolin toward normal human monocytes may be attributable to their high rate of spontaneous DNA strand break formation, to the importance of DNA polymerase alpha for DNA repair in these cells, and to their minute dCTP pools. PMID- 1753101 TI - Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. AB - Human alveolar macrophages (AM) are susceptible to infection with respiratory syncytial virus (RSV), but the infection is abortive after the initial cycles of virus replication. We have investigated if RSV infection of AM results in the production of cytokines TNF, IL-6, and IL-8, all of which may modulate inflammatory and immune responses to the virus, as well as may directly protect respiratory epithelial cells against spread of infection. Within 1 h after interaction with RSV, increased mRNA levels were found for all three cytokines. Peak expression of the mRNAs occurred at 3 to 6 h. The virus most effectively induced TNF mRNA expression greater than IL-6 mRNA greater than IL-8 mRNA, as compared to cytokine mRNA expression induced by bacterial endotoxin. Inactivated virus was almost as effective as live virus in inducing and maintaining increased IL-6 and IL-8 mRNA over 16 h, whereas live infectious RSV was necessary for maintaining TNF mRNA expression over the same time. Protein concentrations of the different cytokines in the supernatants of infected AM reflected the increased levels of mRNA in the cells. Despite the high levels of cytokines with possible antiviral activity (TNF and IL-6) in the AM supernatants, neither supernatants nor rTNF when added to bronchial epithelial cells protected them from infection with RSV. However, TNF, IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the bronchial epithelial cells suggesting that cytokines produced by RSV-infected AM may be more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication of airway epithelium. PMID- 1753102 TI - Characterization of host cell-derived membrane proteins of the vacuole surrounding different intracellular forms of Trypanosoma cruzi in J774 cells. Evidence for phagocyte receptor sorting during the early stages of parasite entry. AB - Trypanosoma cruzi, an obligate intracellular protozoan parasite, exhibits developmental regulation of virulence. Although both noninfective epimastigote and infective trypomastigote stages of T. cruzi enter phagocytic cells via the formation of a parasitophorous vacuole (PV), only the latter developmental stages survive ingestion and perpetuate the infection. To determine whether the membrane composition of PV surrounding these different stages might contribute to differences in the outcome of infection, we identified selected membrane constituents by immunofluorescence and intracellular radioiodination, and studied their incorporation into PV. Complement receptors (CR3) are incorporated preferentially into the PV membrane surrounding serum-opsonized epimastigotes but not culture-derived metacyclic trypomastigotes. FcR are not preferentially incorporated into PV membranes unless epimastigotes or culture-derived metacyclic trypomastigotes are opsonized with anti-T. cruzi antibody. PV surrounding either parasite stage contain beta 1 integrins and lysosomal membrane glycoproteins (lgp). These results indicate that the plasma membrane glycoproteins incorporated into the surrounding PV membrane differ depending upon the stage of parasite being internalized, and that these differences reflect, at least in part, selective ligation of cell surface receptors mediating uptake. Furthermore, they imply that although virulent trypomastigote stages may avoid host cell uptake by conventional phagocytic receptors, i.e., CR3 or FcR, they do not escape fusion with an lgp-containing vacuole where they could still be exposed to lysosomal antimicrobial mechanisms. PMID- 1753103 TI - Activated T lymphocytes from mice infected by lymphocytic choriomeningitis virus display high affinity IL-2 receptors but do not proliferate in response to IL-2. AB - The i.v. injection of mice with lymphocytic choriomeningitis virus (LCMV) initiates a rapid and long lasting immunodepression which can be monitored in vivo or in vitro. Splenic T lymphocytes taken from mice infected for 7 days with LCMV are characterized by a low proliferative capacity in response to Con A stimulation in vitro. In an initial attempt to understand the molecular mechanisms regulating the general anergy induced by the viral infection, we have analyzed the transcription of IL-2 and of p55 IL-2R alpha gene, two genes involved in T cell proliferation. IL-2 gene transcripts were hardly detected after Con A activation of spleen cells from LCMV-infected mice. In contrast, the expression of the gene encoding IL-2R alpha chain was induced as in control noninfected cells. In addition, the expression of the p75 IL-2R beta chain was not modified. The transcripts of the IL-2R alpha and of the IL-2R beta genes were normally translated as high affinity. IL-2R were expressed on the membrane of T lymphocytes from LCMV-infected mice. Despite the finding that these receptors could also internalize IL-2, the exogenous addition of this growth factor did not induce cell proliferation, indicating that the virus-induced blockade is multifocal. PMID- 1753104 TI - Predominance of the prototypic T15 anti-phosphorylcholine junctional sequence in neonatal pre-B cells. AB - The primary antibody response to phosphorylcholine (PC) is dominated by T15 antibodies. There are three families of anti-PC antibodies which can be made in mice: T15, 511, and 603. All use the same H chain V, D, and J segments, but each anti-PC family has a different L chain, as well as a family-specific Vh-D junctional sequence. Here we test the hypothesis that T15 antibodies are dominant because the prototypic T15 V-D junction is generated in pre-B cells more often than the alternative non-T15 V-D junctional sequences. Rearranged IgH genes from DNA derived from fetal or newborn liver pre-B cells and from adult bone marrow pre-B cells of BALB/c mice were amplified by polymerase chain reaction, cloned, and sequenced. DNA from adult splenic B cells was also amplified, for comparison. All V1-DFL16.1 and DFL16.1-Jh1 junctional sequences were analyzed. Fifty-three percent (9/17) of all neonatal pre-B cell V-D junctions with V1 and DFL16.1 had the prototypic T15 junctional sequence, which has no N regions. In contrast, no prototypic T15 V-D junctions were observed in adult pre-B cells, and each junctional sequence was unique. Adult splenic B cells contained an intermediate number of T15-type V-D junctional sequences (7/21). The prototypic D-J junctional sequence used in many anti-PC antibodies was also observed in a high percentage of sequences. The high frequency of T15 junctions in the neonatal pre-B cells can be explained by two observations: 1) N regions are absent in neonatal but not adult junctions and 2) in the absence of N regions, joining of V, D, and J segments may be targeted to short regions of sequence homology near the ends of the genes. This mechanism would preferentially give rise to the T15 V-D and D-J junctions. Preservation of the T15 V-D junction in adult splenic B cells is most likely due to antigenic stimulation of long lived precursors, because a high frequency of T15-type D-J junctions are coexpressed with T15 V-D junctions in splenic sequences. These results predict that T15 anti-PC precursors would be made at a very high frequency in the neonate, and at a much lower frequency in the adult. This may explain why the neonatal period is critical in establishing T15 dominance. PMID- 1753105 TI - Effect of cytokines on switching to IgA and alpha germline transcripts in the B lymphoma I.29 mu. Transforming growth factor-beta activates transcription of the unrearranged C alpha gene. AB - H chain isotype switch recombination is preceded by the appearance of RNA initiating 5' of the specific switch region that will undergo recombination. In an effort to understand the potential function of germline transcripts in switch recombination and whether the regulation of germline transcripts correlates with the regulation of switching, we are studying this process in the murine B lymphoma cell line I.29 mu, which switches, after treatment with bacterial LPS, primarily to IgA and less frequently to IgE. Levels of alpha germline transcripts initiating upstream of alpha switch (S alpha) sequences are elevated in clones of this line that switch well, compared with clones that switch less frequently. Transforming growth factor-beta (TGF-beta) has been shown to increase alpha germline transcripts and switching to IgA expression in LPS-stimulated murine splenic B cells. We now demonstrate that TGF-beta increases LPS-induced switching to IgA by 10-fold at optimal doses and increases the level of alpha germline transcripts 5- to 9-fold in I.29 mu cells. Nuclear run-on analysis shows that this increase is at the level of transcription. Thus, TGF-beta appears to direct switching to IgA by inducing transcription from the unrearranged S alpha-C alpha DNA segment. Germline alpha RNA is quite stable in I.29 mu cells, having a half life of about 5 h, and we find no evidence for further stabilization in the presence of TGF-beta. Levels of epsilon germline transcripts are decreased by TGF beta treatment. IL-4, which modestly increases switching in I.29 mu cells, slightly increases transcription of alpha germline RNA. IFN-gamma, which reduces switching to IgA in these cells, also reduces the level of alpha germline transcripts. IFN-gamma also reduces the level of epsilon germline transcripts induced by IL-4. Our results support the hypothesis that the regulation of transcription of particular switch sequences by cytokines regulates the specificity of recombination. We also present evidence that IL-4 may provide other signals, distinct from transcriptional targeting, that increase LPS-induced switching to IgA. PMID- 1753106 TI - Identification and characterization of a new gene family induced during macrophage activation. AB - In this report, we describe the primary structure and regulation of two novel IFN gamma-inducible genes expressed during the process of macrophage activation. We used the RAW 264.7 cell line to prepare a cDNA library, from which inducible genes were selected by differential hybridization. Two cDNA clones, mag-1 and mag 2 (for macrophage-activation gene-1 and -2), were induced by IFN-gamma treatment in both RAW 264.7 cells and thioglycolate-elicited peritoneal macrophages, but not in the noncytolytic cell line, WEHI-3. A comparison of the nucleotide and deduced amino acid sequences of clones mag-1 and mag-2 with sequences in available data bases revealed no homologs. However, comparison of mag-1 and mag-2 sequences with each other revealed that these genes are homologous, with conserved residues concentrated at the amino terminus. Kinetic analyses revealed similar temporal patterns of induction of mRNA expression for these genes after IFN-gamma treatment. In addition, the genes showed distinct response patterns to the macrophage-activating stimuli IFN-gamma and LPS used either alone or in combination. Analysis of a panel of cell types of various lineages demonstrated that expression of these genes was associated with cellular activation in multiple cell types. As a result of the sequence similarities between these genes, we propose that they define a new family of IFN-gamma-regulated genes in macrophages. PMID- 1753107 TI - The cryptic HLA-DQA2 ("DX alpha") gene is expressed in human B cell lines. AB - Although there are two gene pairs in the HLA-DQ region, DQA1/B1 and DQA2/B2, the latter pair have never been found to be expressed. The DQA2 and DQB2 genes appear to be normal at the DNA sequence level, there being no indication that they should be pseudogenes, and normal splicing occurs when DQA2 is included in a retroviral vector. The putative amino acid sequences of DQA2 and DQB2 have been nearly invariant, raising the questions of how these genes have been maintained normal-appearing and nearly monomorphic if they are not expressed and, if they are expressed, in what cell types are they expressed. We present Northern blot, nuclease protection assay, and mRNA sequence data that demonstrate the existence of spliced DQA2 mRNA in human B lymphoblastoid cell lines. In contrast, we found no evidence of DQB2 mRNA in the same cell lines, nor of DQA2 mRNA in the monocyte line U937 or in activated T cells. PMID- 1753108 TI - IFN-alpha induces autocrine production of IL-6 in myeloma cell lines. AB - IL-6 is a major tumor growth factor in human multiple myeloma. Myeloma cell lines, which have the same phenotypic characteristics and Ig gene rearrangements as the original fresh myeloma cells and whose growth is strictly dependent on exogenous IL-6 similar to fresh myeloma cells, have been reproducibly established. We show here that IFN-alpha stimulated the growth of five of six of these human myeloma cell lines by inducing an autocrine production of IL-6 in myeloma cells. Indeed, IFN-alpha induced IL-6 mRNA accumulation and IL-6 production in myeloma cells and the IFN-alpha-induced growth of these cells was inhibited by anti-IL-6 mAb. Moreover, IFN-alpha made possible the rapid emergence of autonomously growing myeloma cell sublines, which produced IL-6 as an autocrine growth factor. As IFN-alpha has a potential therapeutical interest for multiple myeloma, the present study opens up new directions for studying its effects on the myeloma clone in vivo. PMID- 1753109 TI - Antigen detection in pneumococcal pneumonia. AB - Streptococcus pneumoniae remains the commonest proven cause of community-acquired pneumonia in patients admitted to hospital, but no currently available diagnostic method can be regarded as a gold standard. Microscopy of sputum is usually considered insensitive and poorly specific, and more invasively-obtained specimens are not routinely collected. Cultures of blood and respiratory secretions, and countercurrent immunoelectrophoresis (CIE) and particle agglutination-based assays for capsular polysaccharides in serum and urine specimens, are specific but less than ideally sensitive. Some workers have reported specificity problems when immunoassays are applied to respiratory secretions. New diagnostic methods include detection of pneumococcal C polysaccharide in sputum and urine by ELISA and particle-agglutination assays, and these appear promisingly sensitive and specific in preliminary studies. Clinical assessments are now required to define the role of these techniques in guiding the treatment of individual patients. PMID- 1753110 TI - Prevalence and correlates of diphtheria toxin antibodies among young adults in Israel. AB - The paucity of information about immunity against diphtheria of young adults in Israel prompted us to analyse sera from a random sample of 480 recruits (263 males and 217 females) aged 18-19 years. Antitoxin antibody levels were determined by means of ELISA. Of the recruits 58.1% had antibody values greater than 0.1 IU/ml; 38.5% had amounts between 0.01 and 0.1 IU/ml, which is considered low when using the ELISA method, and 3.3% had less than 0.01 IU/ml. The results of this study suggest that a booster dose of antidiphtheria vaccine should be given to adults in Israel in order to ensure adequate antibody levels. PMID- 1753111 TI - Autonomic neuropathy is common in human immunodeficiency virus infection. AB - We prospectively evaluated autonomic nervous system function in 17 consecutive ambulant patients with HIV infection [mean age (S.D.) 34.5 (5.5) years] and 17 controls matched for sex and age [31.2 (7.4) years]. A questionnaire was administered, and neurological examination and standard bedside autonomic function tests were performed. Eleven of 17 HIV-infected individuals (64.7%) had symptoms suggestive of autonomic dysfunction, particularly urogenital problems. Thirteen of 17 (76.5%) had autonomic neuropathy (one or more abnormal tests), including nine of 11 symptomatic individuals. Only two controls had any autonomic symptoms, and all had normal tests. Autonomic dysfunction is common in those with HIV infection and AIDS. PMID- 1753112 TI - AIDS and tuberculosis in Spain. A report of 140 cases. AB - From January 1984 to October 1990, 140 of 392 (35.7%) patients with the acquired immunodeficiency syndrome (AIDS) were found to have had tuberculosis. One hundred and sixteen were intravenous drug abusers and 16 were homosexual men. Fever, cough, weight loss and generalised lymphadenopathy were common features of their illness. Tuberculin skin tests were negative in 74% and 55% had intraabdominal lymphadenopathy. The chest radiographs showed hilar lymphadenopathy and lower lobe interstitial or alveolar infiltrates, but rarely cavitation. Forty-one of our patients had pulmonary tuberculosis, 38 had extra pulmonary and in 61 it was disseminated. In 80 cases tuberculosis was the presenting feature of AIDS. Tuberculosis usually responded well to chemotherapy. PMID- 1753113 TI - Urinary tract infections caused by Staphylococcus saprophyticus. A matched case control study. AB - Epidemiological and clinical aspects of 270 episodes of urinary tract infection caused by Staphylococcus saprophyticus were studied. The cases were randomly selected and matched consecutively with 276 others of urinary tract infection according to sex, age and temporal occurrence. Such infections were found typically among young women in the outpatient health service. They were common among professionals handling meat products and were especially associated with prior outdoor swimming. Common symptoms of inflammation of the lower urinary tract, haematuria and pyuria were seen more often among patients with S. saprophyticus infections. Some cases of asymptomatic S. saprophyticus infection, however, were seen. We found S. saprophyticus as the cause of 13% upper urinary tract infections, an incidence which is higher than has been reported for other bacteria. Staphylococcus saprophyticus was less correlated to nephrolithiasis and was not a common cause of catheter-induced infections. PMID- 1753114 TI - Meningococcal infection: evidence for school transmission. AB - Intimate contacts of a patient with meningococcal disease are at greater risk of disease than the general population and are offered chemoprophylaxis in order to prevent secondary cases. School contact is not considered a risk factor unless a further case develops. Bacteriological sampling of contacts to identify potential sources of infection is not considered warranted. We have questioned these approaches and investigated the contacts of a 9-year-old child with meningitis caused by sulphonamide-sensitive Neisseria meningitidis group C. Household carriers were not identified but 7/34 classmates were carrying the index strain suggesting that transmission was occurring within this population. The current recommendations for prophylaxis are based on information gathered in socioepidemiological settings, and involving strains which differ from those now prevalent. Such extrapolations may not be justified and further microbiological studies seem warranted to re-examine meningococcal transmission and prophylaxis usage in school children. PMID- 1753115 TI - The use of routine wound swabs and Kardex review for the surveillance of surgical wound infections. AB - Prospective post-operative wound surveillance was carried out in two phases on 1285 patients. A total of 120 infections were documented. In phase I a review of routine swabs and Kardex was conducted in parallel with continuous surveillance. In this phase continuous surveillance detected 31/35 infections and routine swabs and Kardex methods picked up 28/35 infections. In phase 2 continuous surveillance was not carried out and routine swab and Kardex review detected 78/85 infections. Overall II infections were documented following discharge. Continuous surveillance is sensitive but laborious. The method described here would enable infection control nurses to visit patients in whom infections are more likely to occur, and still provide reliable and accurate rates of infections. PMID- 1753116 TI - Herpes zoster associated encephalitis in dialysis patients. AB - Two patients on dialysis because of chronic renal failure who developed herpes zoster associated encephalitis are reported. Both developed overt encephalopathy despite treatment with oral acyclovir for the preceding herpes zoster eruption. The encephalopathy responded rapidly to intravenous acyclovir. PMID- 1753117 TI - Septicaemia caused by Pediococcus pentosaceus: a new opportunistic pathogen. AB - A case of septicaemia caused by Pediococcus pentosaceus is described. The role played by pediococci, and other vancomycin-resistant Gram-positive cocci, in disease states is examined. We suggest that in immunocompromised patients these organisms act as opportunist pathogens. This would appear to be the first reported case of P. pentosaceus septicaemia. PMID- 1753118 TI - Pulmonary nocardiosis concurrent with Pneumocystis carinii pneumonia in two patients undergoing immunosuppressive therapy. AB - Two cases with concomitant pulmonary nocardiosis and Pneumocystis carinii pneumonia are described. The first patient developed pneumonia 3 months after heart transplantation while undergoing standard immunosuppressive therapy with cyclosporin, azathioprine and prednisone. The second patient was treated with chemotherapy and subsequent radiotherapy of the mediastinum for a malignant epithelial tumour. He also received prednisone for paraneoplastic dermatomyositis. Chest X-rays of both patients showed a bilateral interstitial pattern and broncho-alveolar lavage revealed P. carinii. Additional dense and localised pulmonary infiltrates led to suspicion of a further infectious agent, namely, Nocardia asteroides, which was isolated from both patients. Since nocardiosis calls for prolonged treatment, extensive diagnostic measures are needed for its early detection. PMID- 1753119 TI - Actinomycosis of the thigh presenting as a soft-tissue neoplasm. AB - A 14-year-old boy presented with a mass measuring 6 cm x 9 cm, proximal to the patella on the anterior aspect of the knee. Magnetic resonance imaging revealed a 6 x 8 x 4 cm smoothly marginated slightly heterogeneous ellipsoidal mass which displaced musculature, the adjacent cutaneous fat and the quadriceps tendon. At surgery, the mass was noted not to penetrate the superficial surface of the quadriceps tendon and was full of slimy fluid. Histological examination revealed multiple basophilic lobulated granules with homogeneous centres and eosinophilic peripheral clubbed projections. The organisms grown anaerobically were identified as Actinomyces species. The anatomical site of the lesion is very unusual for actinomycosis and the exact route of infection in this patient remains unclear. PMID- 1753120 TI - Mycobacterium malmoense infection in HIV positive patients. AB - Mycobacterium malmoense is a non-tuberculous mycobacterium which has previously been associated with underlying pulmonary pathology and depressed immunity. We describe two patients infected with human immunodeficiency virus from whom M. malmoense was isolated, and discuss its treatment and possible pathogenic role. PMID- 1753121 TI - Multiple brain abscesses caused by Streptococcus bovis. AB - A case of multiple brain abscesses caused by Streptococcus bovis in a 28-year-old man is described. Infected bronchiectasis is presumed to be the source of infection. Streptococcus bovis infection is a rare cause of brain abscess. The aetiology and manifestations of this infection are discussed. PMID- 1753122 TI - Moraxella atlantae bacteraemia in a patient with systemic lupus erythematosis. AB - We describe the first reported case of human infection caused by Moraxella atlantae (formerly known as CDC group M-3) and its successful treatment with intravenous cefuroxime. The isolation and identification of this species, as well as the pathogenesis of the infection, are discussed. It is recommended that isolates of Moraxella species be speciated so that the epidemiological characteristics and pathogenesis of the infections caused by the various species may be understood more completely. PMID- 1753124 TI - Streptococcus faecalis in neonatal infective endocarditis. PMID- 1753123 TI - Descriptive epidemiology of intravenous heroin users--a new risk group for transmission of HIV in India. AB - India is considered to have a low incidence of HIV infection so far. Nevertheless, an epidemic of HIV infection has been reported recently among intra venous drug users (IVDUs) in Manipur, a north-eastern state of India, bordering Myanmar (Burma). This report describes the epidemiology of intravenous drug abuse in the state of Manipur. Four hundred and fifty IVDUs were interviewed. Their age (median 24 years) and sex patterns (95% male) differ from those reported from western countries. It is estimated that there may be approximately 15,000 such addicts in a population of 1.8 million and 50% of them could be positive for HIV. Knowledge of AIDS and its transmission is significantly higher among the addicts than non-addict controls. Free availability of heroin was found to be the major factor responsible for the high rate of addiction. It is presumed that two other neighbouring States which are well-connected to Manipur and also have a common border with Myanmar (part of the 'Golden Triangle') may have a similar problem with HIV infection. PMID- 1753125 TI - Mycoplasma hominis infection of a breast prosthesis. PMID- 1753126 TI - Central venous line infection caused by Brevibacterium epidermidis. PMID- 1753127 TI - Brodie's abscess caused by Eikenella corrodens. PMID- 1753128 TI - Epidural abscess due to Streptococcus milleri and Bifidobacterium species. PMID- 1753129 TI - C-reactive protein sufficient as screening test in bacterial vs. viral infections. PMID- 1753130 TI - Vibrio alginolyticus in the U.K. PMID- 1753131 TI - Fusobacterium necrophorum and Lemierre's syndrome. PMID- 1753132 TI - Louping ill in man: a forgotten disease. AB - Louping ill disease of sheep has been recognised in Scotland for centuries. It causes encephalitis and is transmitted by the sheep tick, Ixodes ricinus. Human infection was first reported in 1934. Thirty-one cases of human infection have now been described. Four clinical syndromes are seen, an influenza-like illness, a bi-phase encephalitis, a poliomyelitis-like illness and a hemorrhagic fever. Certain occupational groups, e.g. laboratory personnel working with the virus and those who kill injected sheep, are at increased risk of acquiring louping ill infection. In many instances, infection is subclinical. Eight new human cases are described. Six were in crofters or shepherds in the north and west of Scotland, one was in a general practitioner in the Western Isles and the eighth was in a butcher in Edinburgh. Louping ill disease should not be forgotten in cases of unexplained encephalitis in those whose lifestyle exposes them to the virus. PMID- 1753133 TI - Decrease of hepatitis A and B virus infections in the population of Okinawa, Japan. AB - In 1988 1282 serum samples were collected from healthy Japanese persons living on Hateruma Island (574 samples) and Iriomote Island (708 samples) in Okinawa, Japan. Serological markers of hepatitis B virus (HBV) infection [hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) were investigated and the findings compared with samples taken in 1980 on Hateruma Island and in 1970 and 1980 on Iriomote Island. The samples collected in 1988 on Iriomote Island were also tested for antibody to hepatitis A virus (anti-HAV) and the findings compared with the results of the 1970 and 1980 surveys. The overall prevalence of HBsAg and anti-HBc was 3.7 and 64.8% for Hateruma Island and 3.8 and 44.9% for Iriomote Island. In both areas the overall prevalence of anti-HBc was lower than in 1980, the decrease being significant for the 10-19 year age group on Hateruma Island and the age groups under 39 years on Iriomote Island. The overall prevalence of anti-HAV had fallen to 50.9%. This remarkable decrease had occurred in children and young adults. These data suggest that Virus A (HAV) and HBV infections have dramatically decreased among children in Okinawa within the past 2 decades. PMID- 1753134 TI - Biopsychosocial aspects of chronic fatigue syndrome (myalgic encephalomyelitis). AB - Fifteen patients, with a primary complaint of chronic fatigue, were referred to a physician by their general practitioners. Psychological distress, measured by simple psychiatric rating scales was common, but specific psychiatric diagnoses, derived from a comprehensive diagnostic interview, occurred less frequently. One questionnaire (Montgomery-Asberg depression rating scale) found emotional distress in 93%, but the diagnostic instrument (Present State Examination) suggested depressive syndromes in only two patients (13%). There were significant occupational difficulties in 87%. No consistently abnormal indices of biochemical or immunological function were found, nor evidence of acute or chronic infection. Chronic fatigue syndrome (CFS) is associated with physical, psychological and social distress. The illness cannot be defined using just one of these dimensions. Such a unilateral approach has resulted in unnecessary controversy over the nature of the 'real' core of CFS. A problem-oriented approach, recognising the multi-factorial and overlapping cause and effect issues in CFS, may be of more benefit to patients. PMID- 1753135 TI - Comparison of clinical and environmental strains of Escherichia coli isolated in Spain. AB - Susceptibilities to antimicrobial agents, bacteriophage lysis patterns and enzymatic polymorphism analysis were used to study genetic variability in Escherichia coli in order to study the relationship between clinical and environmental isolates of the species. Enzymatic polymorphism analysis proved the most useful. The findings were complemented by numerical analysis of phage typing and antimicrobial susceptibilities. PMID- 1753136 TI - Lyme borreliosis in Dutch forestry workers. AB - Serum samples from 127 Dutch forestry workers and 127 matched controls were tested for antibodies against Borrelia burgdorferi in an indirect immunofluorescence assay (IFA). Those of the forestry workers were also tested by Western blotting. The forestry workers were examined clinically for evidence of Lyme borreliosis without the examiner or the workers knowing the results of the laboratory tests. Seroprevalence of B. burgdorferi antibodies among forestry workers (25/127) was significantly higher than among controls matched for age and place of residence (8/127), odds ratio 3.7 (95% CI 1.5-9.7). Of the 25 sera of forestry workers positive in the IFA, 23 reacted with at least five bacterial polypeptides in the Western blot test. According to adapted CDC criteria, seven forestry workers (6%) were classified as being a case of Lyme borreliosis. In only one of them had the diagnosis been made before this investigation. Five persons had a history of erythema migrans, one of arthritis, and one of persistent infection. We conclude that Lyme borreliosis is an occupational disease among forestry workers in the Netherlands, with a three-fold higher seroprevalence than among matched controls. The disease, often not diagnosed among this high-risk group, warrants more attention to achieve early recognition and to prevent late complications. PMID- 1753137 TI - Fatal listeria meningitis in an immunocompromised infant: therapeutic implications. AB - Infection with Listeria monocytogenes is rare in infants and children. Listeriosis has been made a notifiable condition in the State of California since 1985. From January 1985 to December 1990, only seven cases of listeriosis have been reported in children less than or equal to 13 years of age. This brief report summarises the features of a fatal case of listeria meningitis in an immunocompromised 4-month-old infant, discusses diagnostic and therapeutic implications, and describes the other six cases. PMID- 1753138 TI - Successful antibiotic therapy of clostridial septic arthritis in a patient with bilateral total hip prostheses. AB - We report a case of clostridial bacteraemia with infection of a prosthetic hip joint. The patient was successfully treated with IV benzyl penicillin and fucidin followed by oral amoxycillin and probenecid, without surgical intervention. She had no recurrence of her infection in the 19 months before her death. This is believed to be the first reported case of clostridial infection affecting a prosthetic joint. PMID- 1753139 TI - Two cases of Nocardia asteroides sternotomy infection treated with ofloxacin and a review of other active antimicrobial agents. AB - Two patients who developed post-operative sternotomy infections due to Nocardia asteroides were treated successfully with ofloxacin, in vitro susceptibility of the organisms being used as a guide to dosage. The place of this drug in the treatment of infection due to Nocardia asteroides merits further investigation. PMID- 1753140 TI - Mycobacterium haemophilum infection in a patient with AIDS. AB - We report the isolation of a nutritionally fastidious mycobacterial species, Mycobacterium haemophilum, from the skin of a patient with AIDS. The diagnosis of the mycobacterial nature of the patient's lesions was complicated by extensive Kaposi's sarcoma. It is recommended that slowly growing fastidious mycobacteria be sought in any patients with unusual skin lesions. PMID- 1753141 TI - Group A streptococcus endocarditis: report of five cases and review of literature. AB - Group A streptococcus is an uncommon cause of infective endocarditis. We report five probable cases during a 10-year period (1980-1989) from a 750-bed community teaching hospital. None of the patients were drug abusers. Group A streptococcus is the cause of infective endocarditis in between 0 and 5% cases in reported series. Since the introduction of penicillin 69 cases of group A streptococcus endocarditis have been reported in the literature. Clinical details of 14 patients, none of whom were drug abusers, are available. Included are our five cases. Eight patients had no underlying valve lesions. The overall mortality was 21% but only 15% for patients treated approximately. Among the 25 reported IV drugs abusers with group A streptococcus endocarditis and known valve involvement, right-sided heart valves were involved in 19 and left sided in six. The overall mortality was 9%. PMID- 1753142 TI - Neonatal septicaemia due to non-capsulate Haemophilus influenzae in three siblings. AB - I report the case of a woman who, in three successive pregnancies, gave birth to premature infants with septicaemia due to non-capsulate Haemophilus influenzae. All three infants displayed characteristic features of the disease. Maternal antenatal and postnatal management is discussed. PMID- 1753143 TI - Hepatitis A immunity and travel history. AB - Travel histories were taken from 1111 British travellers. Serological testing showed that increasing age and a past history of jaundice were associated with a greater likelihood of travellers being immune to hepatitis A. Neither travel to nor the duration of stay in areas of increased hepatitis A endemicity influenced the level of hepatitis A immunity. It is concluded that travel histories from British citizens normally resident in the U.K. cannot be used to identify those travellers in whom serological prescreening would be of value prior to immunoglobulin prophylaxis. PMID- 1753144 TI - Outbreak of tuberculosis in a poor urban community. AB - A woman from a poor urban community presented recently with pulmonary tuberculosis. Screening of contacts revealed 10 cases of tuberculosis, eight of whom were children. A further 10 children had grade 2-3 positive Heaf tests and were given chemoprophylaxis. Tuberculosis remains a potential problem, particularly in young unimmunized children in deprived areas. PMID- 1753145 TI - Asymptomatic cryptosporidiosis in nomadic shepherds and their sheep. AB - The formed stool samples of 276 asymptomatic members of 36 households of a group of nomadic shepherds and 215 non-diarrhoeal faecal samples from their sheep were examined for cryptosporidial infection by a modified Ziehl-Nielsen technique. Thirty-six (13%) human samples and 37 (17.2%) samples from sheep were positive. A strong possibility of asymptomatic zoonotic transmission of cryptosporidiosis due to prolonged and constant association of shepherds and their sheep was an important finding. PMID- 1753146 TI - Malassezia furfur septicaemia in a child with leukaemia. PMID- 1753147 TI - HTLV-II infection in a Liverpool intravenous drug user. PMID- 1753148 TI - Haemophilus segnis appendicitis. PMID- 1753149 TI - Fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli isolated from human faeces in Switzerland. PMID- 1753150 TI - Ventriculoperitoneal shunt-associated infection. PMID- 1753151 TI - Recurrent plasmodium ovale infection from Papua New Guinea--chloroquine resistance or inadequate primaquine therapy? PMID- 1753152 TI - Fluconazole resistant candida in AIDS. PMID- 1753153 TI - Septicaemia and septic arthritis due to Pseudomonas putida in a neutropenic patient. PMID- 1753154 TI - Clostridium difficile in faecal flora after perioperative prophylaxis with ampicillin or ceftriaxone. PMID- 1753155 TI - Infection in hospital. PMID- 1753156 TI - Advantages and limitations of two software calipers in quantitative coronary arteriography. AB - Software calipers allowing the measurement of the distances between pairs of manually defined picture elements in digitized images may be useful tools for a rapid assessment of the morphology of coronary vessels, e.g. for choosing the appropriate balloon or stent sizes before or during cardiac intervention procedures. In this paper we have studied extensively the advantages and limitations of two manual software calipers--one developed for a PC-based cinefilm analysis workstation, the other for the Philips DCI system. Based on analyses of a perspex vessel phantom with 17 sectors of known size filled with different concentrations (50 and 100%) of the contrast agent and acquired at two kV-levels (68 and 92 kV), it was found that the cinefilm approach is characterized by a very small overall (averaged over te data from three observers) systematic overestimation of 0.03 mm, and the DCI system by a systematic underestimation of 0.07 mm; the worst case accuracy value for an individual observer on frames with 100% contrast dye concentration was 0.20 mm for cinefilm, and -0.34 mm for the DCI, respectively. The overall variabilities in the measurements (precision) were almost identical for the two approaches (overall 0.07 and 0.08 mm for the cinefilm and digital approaches, respectively, and worst case for individual observers on the 100% contrast frames, 0.16 and 0.13 mm, respectively. Inverting the images (bright or dark contrast containing structures) of the phantom at 100% contrast concentration and acquired at 62 kV had no significant effect on the results obtained with the cinefilm analysis system (overall accurary -0.12 mm for both situations), whereas it had on the results from the DCI system (overall accuracies -0.29 (dark vessels on bright background) and -0.08 mm (bright vessels on dark background), respectively). Enhancing the digital images on the DCI with unsharp masking techniques did not significantly influence the measurement accuracy and precision. Finally, it was found that woven dacron, polyurethane and polyvinylchloride catheters filled with 100% contrast dye can be measured with an overall accuracy of better than 0.13 mm on the DCI system. On the PC-based system the woven dacron and polyvinylchloride catheters would result in an overall accuracy better than 0.17 mm, and the polyurethane catheter better than 0.30 mm. The evaluation study has made clear that the nylon catheter should not be applied in QCA-studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753157 TI - Left ventricular wall thickness measurements by magnetic resonance: a validation study. AB - Left ventricular (LV) wall thickness was determined by magnetic resonance (MR) in 15 patients (7 controls and 8 patients with coronary artery disease). End diastolic (ed) and end-systolic (es) wall thickness were measured in a short axis view perpendicular to the LV long axis. Wall thickness measurements were compared to data obtained by digital subtraction angiography (DSA) and M-mode echocardiography (Echo). End-diastolic and end-systolic wall thickness were significantly overestimated by MR (34% and 37%, respectively) when compared to DSA. In contrast, LV end-diastolic and end-systolic chamber diameter were significantly underestimated by MR (25% and 30%, respectively) when compared to DSA. However, fractioned shortening was similar (all NS) for MR (48 +/- 22%), DSA (54 +/- 15%) and Echo (44 +/- 10%), respectively. The mean difference (= accuracy) and the standard deviation of difference (= precision) for LV wall thickness was 0.4 +/- 0.2 cm between MR and DSA, 0.4 +/- 0.3 cm between MR and ECHO and 0.03 +/- 0.1 cm between DSA and ECHO. The correlation of wall thickness between MR and DSA (correlation coefficient r = 0.74, p less than 0.001) and between MR and Echo (r = 0.70, p less than 0.001) was good although the standard error of estimate (SEE) was 17% for MR vs. DSA and 21% for MR vs. Echo. The corresponding SEE for chamber diameter was 16% between MR and DSA and 19% between MR and Echo, respectively. Intraobserver variability for wall thickness determination by MR was excellent (correlation coefficient r = 0.99, p less than 0.001) SEE of 4%. Interobserver variability was also good (correlation coefficient r = 0.90, p less than 0.001) with a SEE of 12%. It is concluded that LV wall thickness and chamber diameter (short axis plane) can be determined by MR with good precision but only satisfactory accuracy. LV wall thickness is significantly overestimated probably due to signals from static blood which might be indistinguishable from the subendocardium. PMID- 1753158 TI - Limitations in the use of five French coronary catheters. AB - Five french (5F) catheters are being widely promoted for use in patients undergoing day case angiography including coronary angiography. Although there are theoretical advantages to this practice there are also potential disadvantages. We reviewed various performance parameters of four different brands of 5F coronary catheter and compared them with performance of the six (6F) and eight french (8F) coronary catheters used in routine coronary angiography. All the 5F catheters performed significantly less satisfactorily than the 6F and 8F catheters. 5F coronary catheters cannot be recommended for routine transfemoral coronary angiography. PMID- 1753159 TI - Percutaneous coronary rotational angioplasty: preliminary clinical and quantitative imaging results. AB - To determine anatomical and functional changes within the first 24 hours after percutaneous coronary rotational angioplasty (PCRA-ROTABLATOR, Biophysics International, USA), we studied 5 patients (4 men) with a mean age of 55 years (range 52-59) using quantitative coronary angiography, coronary flow reserve from digitized coronary angiograms, quantitative left ventricular angiography, and 99mTechnetium-MIBI SPECT imaging before PCRA, immediately after, and 24 hours after. The minimal luminal diameter and obstruction area showed a moderate increase immediately after PCRA, with a substantial further improvement after 24 hours. The mean coronary flow reserve before PCRA and 24 hours after (1.65 +/- 0.31 vs. 1.81 +/- 0.37; p = NS) remained unchanged. Although the global ejection fraction showed slight impairment immediately after PCRA, this was restored 24 hours later. Only the contribution to regional ejection fraction in the regions supplied by the treated coronary artery attributed to the decrease of global ejection fraction. Before and after PCRA, Tc-99m MIBI tomography performed at rest revealed no perfusion defects in the myocardial regions related to the coronary arteries undergoing the intervention. PMID- 1753160 TI - Left ventricular dual-energy digital subtraction angiography: a motion immune digital subtraction technique. AB - Digital subtraction angiography (DSA) allows quantitative analysis of ventricular function via densitometric and parametric imaging techniques. However, DSA is limited by the artifacts in temporal subtraction images that result from patient and cardiac motion. Dual-energy subtraction imaging is insensitive to motion. This study evaluated the initial application of dual-energy subtraction in cardiac patients. The image quality of dual-energy subtraction left ventriculograms obtained from a pulmonary artery injection of contrast was assessed in 13 patients, ranging in weight from 54 to 100 kg. The dual-energy images were compared with left ventricular images obtained using standard left ventricular injection cine angiography. End-systolic and end-diastolic ventricular volumes calculated from the cine (C) and dual-energy (DE) images using the Area-Length method were compared. The resulting regression line was DE = 0.98 C+ 7.0 ml, and the r value was 0.987. Dual-energy subtraction provided good left ventricular visualization, free from misregistration artifacts, even during patient motion. PMID- 1753161 TI - Should the exercise test (ET) be performed at discharge or one month later after an episode of unstable angina or non-Q-wave myocardial infarction? AB - The diagnostic and prognostic value of symptom limited exercise tests (ET) performed before discharge and after one month were compared in men admitted to hospital after an episode of unstable angina or a non-Q-wave myocardial infarction (MI). A 'Positive ET' was defined as either a maximal work load below 100 W or ST-depression greater than or equal to 0.1 mV in 1-2 leads below 130 W or ST-depression greater than or equal to 0.1 mV in more than 2 leads at any load at the ET. During follow-up, severe angina was the only indication for coronary angiography and revascularization. There were no significant differences in diagnostic findings between the tests--Positive ET in 47% and Negative ET in 25% at both ETs. The occurrence of MI or death and the need of revascularization were related to signs of ischemia at both ETs. There were no differences in prognostic value between the early and late tests regarding MI or death or future severe angina during the 11 months' follow-up after the one month ET. However, half (10%) of the overall event rate (20%) during the one year follow-up occurred during the first months. The risk of these events could be identified by the predischarge but, for obvious reasons, not by the one month ET. Therefore, the present study suggests that a symptom limited ET should be performed before discharge in men stabilized after an episode of unstable angina or non-Q-wave MI. PMID- 1753162 TI - Assisted hatching of human embryos. AB - There are benefits as well as drawbacks of zona pellucida breaching. Narrow gaps in the zona may cause disintegration of the hatching trophectoderm, when embryos are cultured in vitro. An increase in the formation of monozygotic twins following micromanipulation may also occur, due to the forced separation of the inner cell mass during blastocyst expulsion in utero. Mouse studies indicate that one or several narrow zona openings (less than 5 microns) are detrimental. Such embryos may become trapped during hatching but may be rescued by drilling an additional larger gap elsewhere on the zona. The use of acidic Tyrode's solution for clinical assisted hatching of eight-cell embryos is currently under investigation. The findings suggest that large holes are efficient for promoting hatching (at least one-fourth of the embryos implanted thus far) and that embryos with unthinned zonae (those with normally the poorest prognosis) benefit mostly from assisted hatching. Results also indicate that embryos with the best zona morphology should be replaced without micromanipulation. PMID- 1753164 TI - Syringe-associated toxicity of culture media on mouse and monkey preembryos. PMID- 1753163 TI - Effects of sera from patients given various anesthetics on preimplantation mouse embryo development in vitro. AB - This study compared the effects of sera from patients given various anesthetics on in vitro mouse preimplantation embryo development. Patients electing bilateral laparoscopic tubal sterilization were subjected to general anesthesia with nitrous oxide (N2O) that included either isofluorane (ISO/N2O) as an inhalant or fentanyl or morphine (FEN/MOR/N2O). The addition of sera collected 1 hr after anesthetic induction significantly reduced the numbers of two-cell mouse embryos that developed to blastocyst in the ISO/N2O group as compared to that of preanesthesia sera. In contrast, no detrimental effects were revealed from sera of patients given FEN/MOR/N2O. Comparison of sera from patients given ISO/N2O and FEN/MOR/N2O for laparoscopic oocyte retrieval and from patients given spinal anesthesia and/or i.v. sedation for ultrasonic retrieval also revealed a decrease in mouse embryo development in the ISO/N2O group, but no differences were seen in the other anesthetic regimens. ISO/N2O anesthesia was also associated with a significantly decreased fertilization rate of mature oocytes retrieved. However, no significant effect of ISO/N2O anesthesia on IVF pregnancy rates could be demonstrated. These studies indicate that embryo toxic effects can be detected in sera from patients given ISO/N2O and that this anesthetic may be detrimental to the success of in vitro fertilization and embryo transfer. PMID- 1753165 TI - The reproductive outcome following a superhigh response to stimulation in gamete intrafallopian transfer program. AB - A retrospective analysis was carried out to assess the outcome of gamete intrafallopian transfer (GIFT) in cycles when more than 10 oocytes were retrieved (superhigh responders) from October 1987 through June 1989. There were 276 (13%) cycles with more than 10 oocytes retrieved among all GIFT cycles initiated during the period. Clomiphene citrate and gonadotropin were employed for ovarian stimulation in 105 (38%) cycles, and gonadotropin releasing hormone agonist in the remaining 171 (62%) cycles, employing either the flare (104 cycles) or the pituitary down-regulation (67 cycles) protocol. A maximum number of four oocytes was transferred per GIFT (3.5 +/- 0.4). The mean number of oocytes retrieved was 14.7 +/- 4.4 (range, 11 to 35). A significantly younger age group (less than 30 years) of patients was noticed in the study (31.9), and fewer women aged 40 and over (6.2%), compared to the general population of our patients. The pregnancy rate was 33.3% (n = 92) per cycle, with a delivery rate of 23.6% (n = 64) per cycle; the pregnancy loss rate was 30.8%. The reproductive outcome was lower in women aged 40 and over (pregnancy rate was 23.5%, but delivery rate was only 5.8% per cycle). The delivery rate was lower in the clomiphene citrate- and gonadotropin-stimulated cycles (51.7% per pregnancy) in relation to gonadotropin releasing analogue and gonadotropin cycles (76.6% per pregnancy) and significantly so compared with the pituitary down-regulation protocol (83.3% per pregnancy). We conclude that a superhigh response develops more in younger women, and in such circumstances, the use of pituitary down-regulation with gonadotropin releasing hormone will improve the reproductive outcome. PMID- 1753166 TI - Developmental capacities of two-cell mouse embryos frozen by three methods. AB - The following three methods were evaluated in order to obtain a most efficient freezing protocol for the preservation of two-cell mouse embryos: (a) slow cooling and slow thawing in 1.5 M dimethyl sulfoxide, (b) slow cooling and fast thawing in 1.5 M propanediol (PROH), and (c) ultrarapid freezing and fast thawing in either 3.5 M DMSO or 3.0 M PROH. In the slow-cooling procedures (a and b) ice nucleation (seeding) was induced manually or automatically. With method a, only a slight difference, 51.8% for manual and 58.9% for automatic seeding, was observed in survival rates, while the development to blastocysts was significantly affected: 35.4% with manual and less than 10% with automatic induction (P less than 0.001). Method b gave high survival (86.2%) and developmental rates (69.0%) with manual seeding compared with automatic seeding (20.7 and 9.8%, respectively; P less than 0.001). Using protocol c, higher survival and developmental rates were obtained with DMSO (84.8 and 55.9%) than with PROH (39.8 and 19.4%, P less than 0.001). These results demonstrate that inducing nucleation manually is superior to the use of a highly sophisticated autoseeding system and that method b with manual seeding is most effective in preserving the developmental capacity of two-cell mouse embryos after freezing and thawing. There is evidence that this is also true of human embryo cryopreservation. PMID- 1753167 TI - The use of transvaginal ultrasound to aspirate bilateral hydrosalpinges prior to in vitro fertilization: a case report. AB - Transvaginal ultrasound has recently been introduced diagnostically for follicular monitoring, early pregnancy localization (1), pelvic structure identification, early fetal development (2), detection of ovarian enlargement in postmenopausal women (3), and detection of endometrial carcinoma (4). Transvaginal ultrasound has had a major impact on patient monitoring and treatment for in vitro fertilization and embryo transfer (IVF/ET). Therapeutically transvaginal ultrasound has been introduced for oocyte retrieval and selective pregnancy reduction. The purpose of this paper is to present the therapeutic use of transvaginal ultrasound to aspirate large bilateral hydrosalpinges which complicated embryo transfer during an in vitro fertilization cycle. PMID- 1753168 TI - Improved fertilization rates of human oocytes in coculture. AB - Passaged human tubal ampullary epithelial cells from cell lines were used to evaluate fertilization rates and the support of early human embryonic cleavage in vitro. A total of 225 mature oocytes from 32 patients was used in this study. Oocytes from each patient were equally allotted at random to two groups. One hundred thirty-two oocytes were inseminated in the presence of passaged human ampullary cells, while 123 oocytes were inseminated in culture medium alone. Fertilized oocytes were transferred to tubal ampullary cell monolayers and monitored for up to 48 hr. Eighty-five percent of oocytes fertilized in coculture, as compared to 67% in medium alone (P less than 0.01). A higher percentage of good-quality embryos was observed in cocultures than in controls (79 vs 67%; P less than 0.05). Binding of sperm to ampullary monolayer cells was observed. Human ampullary-cell cocultures may be useful to improve fertilization rates and embryonic viability and thus increase take-home baby rates for in vitro fertilization programs. PMID- 1753169 TI - A case of human pregnancy after microinjection of capacitated sperm into the perivitelline space. AB - Microinjection of capacitated sperm into the perivitelline space of oocyte was offered to one couple with persistent infertility of mixed origin. The husband's semen was subnormal, whereas his wife had definitive tubal occlusion and polycystic ovaries. Four previous in vitro fertilization (IVF) attempts were performed but no fertilization was obtained. After superovulation, 13 oocytes were collected. Ten were submitted to microinjection and two were damaged during the procedure. One of the remaining eight had two pronuclei 18 hr after microinjection and progressed to a four-cell embryo after 48 hr. After reimplantation, a normal pregnancy was initiated, caryotype (46XX) was checked at 17 weeks. A normal and healthy girl has been delivered at term. PMID- 1753170 TI - Reliability of gender determination using the polymerase chain reaction (PCR) for single cells. AB - Contamination with extraneous DNA sequences is a frequent problem when performing PCR analysis of single cells. This report describes our experience with eliminating contaminating DNA sequences from PCR reagents for the purposes of gender identification. We have used amplification of Y-specific sequences to identify the gender of single human amniocytes. Female cells consistently showed no Y-specific bands but only 80% of male cells showed the expected intense Y specific band. This phenomenon could lead to incorrect gender identification of single cells. We developed a technique of simultaneous amplification of X- and Y specific sequences to prevent misdiagnosis because of failed PCR, which allows accurate preimplantation gender determination for women at risk for conceiving children with X-linked genetic diseases. We analyzed the gender of 141 consecutive single cells in a blinded manner without a single incorrect gender assignment. PMID- 1753171 TI - The effect of leuprolide acetate on steroidogenesis by granulosa and theca cells in vitro. AB - Enhancement of follicular response to controlled ovarian hyperstimulation for human in vitro fertilization (IVF) has been suggested following pretreatment with leuprolide acetate (LA). However, additional human menopausal gonadotropin (hMG) is required to achieve follicle maturity in the presence of LA. We studied the effect of LA on steroidogenesis of granulosa and theca cells in vitro. Human granulosa cells obtained from IVF follicular fluid aspirations were cultured for 14 days in the presence and absence of human chorionic gonadotropin (hCG). hCG significantly enhanced progesterone (P) and estradiol (E2) production by the cells, however, the addition of LA in concentrations of 10, 100, and 1000 ng/ml had no effect. Porcine granulosa cells were cultured for 48 hr in the presence and absence of follicle stimulating hormone (FSH) with the addition of LA at the same doses. LA did not affect the FSH-induced increase in P production. Porcine theca cells were cultured for 48 hr in the presence and absence of hCG. The addition of LA did not affect androstenedione (A) production by these cells. We conclude that in this dynamic model in vitro, LA does not inhibit or stimulate P or E2 production by granulosa or A production by theca cells. PMID- 1753172 TI - Pregnancy in a premature ovarian failure patient with donated oocytes from a 40 year-old sibling: a case report. PMID- 1753173 TI - Twin in vitro fertilization (IVF) pregnancies: spontaneous intrauterine abortion after selective second-trimester termination of ectopic intraabdominal pregnancy. PMID- 1753174 TI - Successful ovarian superovulation for in vitro fertilization in a patient with an undiagnosed intrauterine pregnancy. PMID- 1753175 TI - Pregnancies following direct oocyte-sperm transfer (DOST): a simple alternative to conventional in vitro fertilization (IVF) PMID- 1753176 TI - Conformational constraints involved in MHC class I restricted antigen presentation. AB - The realization that class I-restricted antigen presentation can be mimicked using synthetic peptides and the description of the class I three-dimensional structure has provided a basis with which to study the conformational constraints associated with cytotoxic T cell (CTL) recognition. Recent experiments have suggested that antigenic fragments can bind to class I molecules in extended conformations. This binding is dependent on the presence of predominant motif arrangements in the peptides which are likely to correspond to specific subsites within the class I binding cleft. Changes within this cleft can affect T cell receptor recognition by inhibiting peptide binding or by altering the conformation of the presented peptide. These changes can result in dramatic modifications in peripheral T cell recognition and in the thymic development of the T cells themselves. Consequently, class I molecules apparently control the T cell response via their effect on the binding and conformation of the presented peptide determinants. PMID- 1753177 TI - Nasopharyngeal carcinoma. AB - Carcinoma of the nasopharynx is a rare disease that presents the physician with a difficult diagnostic and therapeutic challenge. The purpose of this report is to review the natural history, clinical evaluation, and treatment of carcinoma of the nasopharynx. PMID- 1753178 TI - Hib immunization of children. PMID- 1753179 TI - Calcified mucocele of the appendix presenting as ureteral obstruction. AB - Mucocele of the appendix, a rare lesion, occurs in 0.3% of patients undergoing appendectomy. Only 46 cases of calcified mucocele have been reported. Complications reported include appendiceal intussusception, rupture resulting in acute abdomen, and infection. We report the case of a 74-year-old man with a calcified mucocele of the appendix that was discovered in the evaluation of a ureteral obstruction. During exploratory surgery, the patient was found to have a 6 x 5 cm appendiceal tumor and underwent a right ileocolectomy. Pathologic examination showed calcified mucous cystadenoma of the appendix. Calcification of a mucocele is believed to denote chronicity. Our case is the first report of ureteral obstruction secondary to calcified mucocele and the second calcified mucocele to be seen on computerized tomography. Calcified mucocele should be included in the differential diagnosis of any calcified tumor in the right lower quadrant. PMID- 1753180 TI - Of mice, men, and physicians. PMID- 1753181 TI - ECG of the month. Innocent abnormality. Early repolarization pattern. PMID- 1753182 TI - Remain true--pride in medicine. PMID- 1753183 TI - Pregnancy from cryopreserved embryos: an important new aspect of assisted reproduction. AB - Assisted Reproduction techniques have become well-established methods of treating infertility in the decade since their inception. The gradually improving efficacy of these procedures has made the risks of multiple pregnancy a serious concern. Cryopreservation of "extra" embryos has been developed to counter this problem, but has led to new difficulties. Assisted Reproduction in Kentucky has kept pace with progress worldwide; the first Kentucky live birth from transfer of cryopreserved embryos is reported. PMID- 1753184 TI - Splenectomy for hematologic disorders: a 20 year experience. AB - A retrospective chart analysis was conducted for all patients undergoing splenectomy for hematologic disorders at the Baptist Hospitals of Louisville between 1970 and 1989. Fifty-nine charts comprise the basis of this review. Variables considered included disease entities treated by splenectomy, indications for splenectomy, and morbidity and mortality associated with the surgery. Additional variables evaluated were splenic weight, estimated blood loss at surgery, technique of splenectomy, and drainage of the splenic bed. The authors found a high correlation of splenic weight to the hematologic disorder treated. Larger spleens were associated with greater blood loss at surgery. Preliminary splenic artery ligation did not reduce the operative blood loss in patients with massive spleens. Drainage of the splenic bed was not associated with postoperative bleeding or intra-abdominal abscess. The low morbidity (22%) and mortality (3.4%) compares favorably to other published studies, demonstrating that splenectomy for hematologic disorders may be safely performed in the community hospital setting. PMID- 1753185 TI - Indications and uses of the noninvasive vascular laboratory: cerebrovascular and venous evaluation. AB - Noninvasive vascular laboratory tests are highly accurate in diagnosing cerebrovascular arterial and extremity venous disease. These tests can also locate and grade the severity of the disease. Noninvasive studies are preferable to invasive angiographic procedures for the initial evaluation of patients who may have carotid artery disease, deep venous thrombosis, or venous valvular insufficiency. Arteriography of the extracranial cerebrovascular arteries should be used only for operative candidates who have severe disease of the carotid artery as determined by noninvasive studies. Venography is indicated in the few cases in which tibial vein thrombosis cannot be excluded by the noninvasive tests, or in patients undergoing evaluation for venous surgery (valvuloplasty or valve transplant). PMID- 1753186 TI - View-point based suppression of speech in the practice of medicine in the United States. PMID- 1753187 TI - Physician Payment Reform. PMID- 1753188 TI - Errors of deglutition--real and imagined; or, don't forget the psyche. PMID- 1753189 TI - Can meta-analysis help uncertainty in surgery for otitis media in children. AB - While otitis media is perhaps the most common disease of childhood that receives medical attention, there is little agreement concerning the efficacy of the medical and surgical therapies employed to try to alleviate its symptoms or hasten its natural resolution. Because various surgeries including adenoidectomy, myringotomy, and insertion of tympanostomy tubes are frequently involved in the treatment of otitis media with effusion (OME), it is likely the most expensive condition being managed in national terms. In an attempt to elucidate the most appropriate management of this condition, a meta-analysis was attempted to the 12 randomized control trials of surgical treatments for OME in children, published between 1966 and 1990. Heterogeneity both in the populations and comparisons studied and in the outcomes presented made meta-analysis an inappropriate method for clarifying this area of clinical uncertainty. Important elements in the design of randomized control trials that should be included in future studies of treatment for OME are therefore discussed. PMID- 1753190 TI - Cholesteatoma in children: results in open versus closed techniques. AB - Cholesteatoma in children presents characteristics that differentiate it from the adult condition. Surgery has been performed in 55 ears. The main reason for referral was otorrhoea (83 per cent), either alone (29 per cent) or with hearing loss (54 per cent). Apart from three cases with an intact eardrum, a perforation was always present mostly posterior-superior (50 per cent). Open techniques were performed in 27.3 per cent of the ears and the closed technique in 72.7 per cent. Only in 18 per cent of cases was the ossicular chain normal and mobile. The attic was occupied by cholesteatoma in 79 per cent. Recurrence took place in 37 per cent and 13 per cent of the closed and open techniques respectively. Open techniques tend to be employed in the presence of extensive disease, whereas the closed technique is reserved for those with a more localized problem. PMID- 1753191 TI - Direct referral hearing aid provision in the over sixties age group. AB - A prospective study was designed in which General Practitioners were issued with a standard referral letter for hearing aid provision. Unknown to the General Practitioner an independent otolaryngologist assessment was obtained at the time of first attendance. Three hundred consecutive patients selected by General Practitioners applying these guidelines were seen in a designated hearing aid clinic staffed by audiological technicians of senior grade or above. Referral pro formata were incomplete in 75 patients who were not assessed. Ninety-four patients (31 per cent) (95 per cent confidence interval 29-36 per cent) were accepted by the audiologist. Obstructing wax was the most common criterion failed. Clinical agreement between audiologist and otolaryngologist was 57 per cent greater than chance. None of the cases of clinical disagreement altered treatment. A direct referral system as proposed could have processed only 31 per cent of 300 referrals. However, experienced technical staff reliably detected otological pathology and with aural toilet facilities 91 per cent of 225 patients (confidence interval 88-94 per cent) were aided. PMID- 1753192 TI - Experience with a subcutaneous implantable bone conduction hearing aid (Xomed Audiant) in a district general hospital. AB - Patients with a conductive hearing loss may find conventional hearing aids unsatisfactory for a variety of reasons. Efforts to overcome some of these difficulties have led to the development of the osteointegrated hearing aid. Implantable bone conduction hearing aids are an important advance in the treatment of well selected patients. Only 18 patients, who have been implanted with the Xomed Audiant bone conduction hearing aid, have so far been reported on in the UK. This report concerns a further six patients who have been implanted in one centre. Five of these patients continue to use their Audiant hearing aid 14 to 24 months after being fitted. They regard it to have significant advantages over their previous hearing aids. Four of the five patients use an ear level processor. Two of the patients who had previously used conventional bone conduction hearing aids now use the ear level processor. PMID- 1753193 TI - Functional endoscopic sinus surgery in the management of chronic rhinosinusitis. An objective assessment. AB - Considerable clinical success has been claimed for functional endoscopic sinus surgery but objective assessment of prospective series is lacking in the literature. Twenty-four patients with chronic rhino-sinusitis underwent assessment of symptoms by visual analogue scoring, nasomucociliary function by ciliary beat frequency, olfaction by qualitative olfactometry and nasal airway resistance by anterior rhinomanometry pre- and post-operatively. This demonstrated a significant improvement in all symptoms examined and in ciliary beat frequency. Quantitative olfaction and anterior rhinomanometry were not improved despite diminished symptoms. These results offer quantitative evidence of clinical improvement following functional endoscopic sinus surgery which supports the pathophysiological concepts on which the technique is based. PMID- 1753194 TI - Adult tonsillectomy--results and patient selection. AB - One hundred and thirty two patients who had undergone tonsillectomy for recurrent sore throats were evaluated by a questionnaire regarding the effectiveness of their operation. There were 98 respondents of whom 88.8 per cent were satisfied with the benefit gained. Smoking habit did not affect the post-operative satisfaction rate. Dissatisfied patients were more likely to have changed their General Practitioner recently and more likely to have had multiple hospital referrals in the past. Improved patient satisfaction rates may be achieved by more careful assessment of patients with the latter characteristics. PMID- 1753195 TI - Acute epiglottitis in the adult. AB - Acute epiglottitis in the adult is a rare disease, which has shown an appreciable increase since the sixties and in our locality since 1984. We present a review of the cases registered in our hospital, analyzing their aetiology, evolution and treatment. The disease is most likely to be suspected in the presence of any patient having a sudden dysphagia, especially if he shows symptoms of an acute infection and a lack of oropharyngeal pathology. PMID- 1753196 TI - Alternative method of application of topical preparations in otitis externa. AB - Management of otitis externa and the discharging mastoid cavity accounts for a significant proportion of the ENT out-patient workload. A simple technique of topical application of dermatological preparations is described which is easy and effective. PMID- 1753197 TI - Exostosis of the external auditory canal: an interesting histopathological finding. AB - Perforation of the tympanic membrane is a frequent complication of surgery for exostoses of the external auditory canal. We report an unusual histopathological finding in a temporal bone containing external canal exostoses which suggests that some of these perforations may be unavoidable. PMID- 1753198 TI - Young's procedure in the treatment of epistaxis. AB - Intractable epistaxis associated with septal perforation is a difficult problem to treat, particularly if nose-picking appears to be associated. Two such cases are presented in which Young's procedure of nasal closure was used to prevent epistaxis. Although the procedure was fully successful in only one patient, we feel the procedure has a part to play in the management of such cases of epistaxis. PMID- 1753199 TI - Foreign body in the tongue: an unusual site for a common problem. AB - Foreign bodies in the upper aerodigestive tract represent one of the commonest ENT emergencies. A case report of a fish bone penetrating the anterior tongue is presented which exemplifies this frequent problem, but at a rare site. PMID- 1753200 TI - 'Priapism' of the turbinates: a cause of nasal obstruction in sickle cell anaemia. AB - A cause of nasal obstruction in sickle cell anaemia not previously described in the literature is presented. The pathophysiology is the same as in priapism because of the similarities in the vascular arrangement of the turbinate and the penis. Various treatment options are considered but the best results were achieved by surgical reduction of the inferior turbinates. PMID- 1753201 TI - Papillary adenocarcinoma of the nasopharynx. AB - The first case of low-grade papillary adenocarcinoma of the nasopharynx is described from an area where carcinoma in the nasopharynx is endemic. Clinicopathological features are detailed and differences between the prevalent nasopharyngeal cancer and low-grade nasopharyngeal papillary adenocarcinoma are emphasized. This tumour requires positive identification as surgical management is necessary to avoid the possibility of future recurrence. PMID- 1753202 TI - Giant cell tumour of the sphenoid sinus: an unusual skull base tumour. AB - An unusual skull base tumour is presented. Intraoperative smears made the diagnosis and dictated a change in surgical strategy. Giant-cell tumours of the sphenoid bone are discussed, together with current management. PMID- 1753203 TI - Bilateral thoracic empyema complicating adult epiglottitis. AB - Haemophilus influenzae is a common cause of epiglottitis and meningitis in children and exacerbation of chronic bronchitis in adults. However, the ability of this organism to cause serious infections in adults is less well recognized. We report a case of a 34-year-old previously healthy female who presented with epiglottitis and later developed bilateral empyema; both blood and pleural fluid grew Haemophilus influenzae. PMID- 1753204 TI - Intraglandular toxoplasmosis lymphadenitis of the parotid gland. AB - Toxoplasmosis is a protozoan infection manifested by systemic findings as well as generalized or localized lymphadenopathy. Although lympadenitis is the most common clinical form, involvement of the intraglandular nodes within the parotid gland found is a rare occurrence during the course of the disease. This unusual form may mimic a parotid mass, and can cause difficulties in differential diagnosis. In this article, a case of intraglandular parotid lymphadenitis which developed due to toxoplasmosis is presented, and the relevant literature is reviewed. PMID- 1753205 TI - Giant cervical cyst: presenting symptom of an occult thyroid carcinoma. AB - A case of giant lateral cervical cystic metastasis from occult thyroid carcinoma mimicking branchial cleft cyst is reported. Lateral cervical cystic metastases arising from occult thyroid carcinoma and their ultrasonic differentiation from true cysts are discussed. PMID- 1753206 TI - Chloral hydrate and middle ear pressure. PMID- 1753207 TI - Kikuchi's necrotizing lymphadenitis. PMID- 1753208 TI - Submucous resection as an outpatient procedure. PMID- 1753209 TI - Isolation and partial characterization of a protein with HMG-CoA reductase phosphatase activity associated with rat liver microsomal membranes. AB - Several rat liver HMG-CoA-reductase (HMG-CoA-Rd) phosphatase activities have been shown to be associated with the endoplasmic reticulum. These activities were not due to glycogen contamination, as judged not only from different patterns of solubilization of the microsomal membranes and the glycogen pellet but also by differential centrifugation behavior under standard conditions and in a sucrose gradient. We present evidence that at least three forms of protein phosphatase are associated with microsomal membranes: a polycation-stimulated type 2A phosphatase, a type 2C phosphatase, and a non-2A, non-2B, non-2C phosphatase. This last HMG-CoA-Rd phosphatase activity corresponding to an 85 kDa protein was partially purified by several chromatographic procedures. The IC50 value for the inhibition of the HMG-CoA-Rd phosphatase by I-2 was 10-fold higher than for the inhibition of the purified type 1 catalytic subunit from rabbit skeletal muscle. The microsomal HMG-CoA-Rd phosphatase activity was slightly affected by the protein inhibitor that inhibits type 2A activity when HMG-CoA reductase is the substrate. The HMG-CoA-Rd phosphatase activity is spontaneously active and it is not reactivated in the presence of Mg2+ or polycations. The holoenzyme does not contain the inhibitor-2 and it is not reactivated by incubation with ATP and glycogen synthase kinase-3. Proteolytic treatment of the enzyme yielded a polypeptide fragment of low Mr (37 kDa) with reduced activity. A model of holoenzymatic HMG-CoA-Rd phosphatase and its relation to the microsomal membranes is presented. PMID- 1753210 TI - Isolation and characterization of calmodulin-inactivating cholesterol hydroperoxides. AB - A series of cholesterol hydroperoxides has been prepared and tested as inactivators of calmodulin. Two previously undescribed compounds, tentatively identified as 20-(R)-25-dihydroperoxy-5-cholesten-3 beta-ol and its 20-(S) isomer inactivate calmodulin with 50% loss of activity at 5-10 microM. Cholesterol derivatives with a single hydroperoxy group at C-20 or C-25 are less effective, while 7 alpha-hydroperoxy-cholesterol and 25-hydroxy-cholesterol are inactive. The side-chain hydroperoxide compounds were isolated from a mixture shown earlier to suppress formation of fatty streaks in aortas of rabbits fed a diet supplemented with cholesterol. PMID- 1753211 TI - Interruption of the enterohepatic circulation of bile acids stimulates the esterification rate of cholesterol in human liver. AB - The activity of acyl CoA: cholesterol acyltransferase (ACAT), which catalyzes the esterification of cholesterol, was studied in liver microsomes obtained from cholestyramine-treated gallstone patients (n = 12) and patients with Crohn's disease who had undergone partial ileal resection (n = 11). Gallstone patients (n = 33) and gallstone-free subjects undergoing cholecystectomy because of polyps of the gallbladder (n = 8) served as controls. The mean levels of the ACAT activity were the same in the gallstone and the gallstone-free patient groups (6.0 +/- 0.4 and 6.1 +/- 1.1 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system the activities were increased four- to fivefold in both groups. The ACAT activity tended to be increased in the cholestyramine-treated patients (8.1 +/- 1.8 pmol/min per mg protein), and was significantly enhanced (P less than 0.005) in the ileal-resected patients (12.3 +/- 2.3 pmol/min per mg protein). When the enzyme activity was determined with added exogenous cholesterol, it was significantly higher compared to the controls in both the cholestyramine-treated patients and the patients with ileal resection (57.9 +/- 11.6 and 50.0 +/- 10.3 pmol/min per mg protein, respectively). The content of free and esterified cholesterol in liver homogenates and microsomes was not significantly different between the patient groups. We conclude that ACAT activity is increased in patients with interruption of the enterohepatic circulation of bile acids, and speculate that this reflects a stimulated uptake of lipoprotein cholesterol and may indicate that more cholesteryl esters are incorporated into very low density lipoproteins. PMID- 1753212 TI - Bile acids of marsupials. 2. Hepatic formation of vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic acid) from chenodeoxycholic acid in a marsupial, Trichosurus vulpecula (Lesson). AB - Free vulpecholic acid (1 alpha,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic) is the major biliary component of the Australian opossum (Trichosurus vulpecula), accompanied only by a few percent of its taurine conjugate. In order to exclude a microbial involvement in its formation (i.e., secondary origin) four sets of experiments were performed. It was found that a) the level of vulpecholic acid remained unchanged in the bile of opossums fed with neomycin and kanamycin for 7 days prior to bile collection; b) it also remained unchanged after long bile drainage; c) in opossums prepared with biliary cannula, intraportally injected [24-14C]chenodeoxycholic acid was transformed to [24-14C]vulpecholic acid; and d) in a similar experiment, the detectable transformation of [1 alpha,2 alpha 3H2]cholesterol to vulpecholic acid was observed. In experiment c) 28-66% of the administered radioactivity was secreted in 2 h in the form of free biliary vulpecholic and chenodeoxycholic acids. Only a trace amount of the corresponding taurine conjugates (approximately 0.4%) was formed. Moreover, rapidly declining specific radioactivity of the unconjugated chenodeoxycholic acid indicated its probable participation in the native formation of vulpecholic acid. PMID- 1753213 TI - Intestinal lymph and plasma lipoproteins in the preruminant calf: partial resolution of particle heterogeneity in the 1.040-1.090 g/ml interval. AB - Our previous studies in the preruminant calf have provided evidence for the heterogeneity of lipoprotein particles in the 1.040-1.090 g/ml density interval in both plasma and postprandial intestinal lymph (Bauchart, D. et al., 1989. J. Lipid Res. 30: 1499-1514; and Laplaud, P. M. et al., 1990. J. Lipid Res. 31: 1781 1792). We therefore attempted to resolve this heterogeneity by use of heparin Sepharose affinity chromatography. Experiments were performed on three calves; portal vein plasma and intestinal lymph were obtained simultaneously 10 h after a meal, i.e., at peak lipid absorption. In both fluids, the chromatographic profile presented three fractions, I, II, and III. Fraction I was characterized by the presence of cholesteryl ester-rich particles (approximately 35-37% of lipoprotein mass), which migrated electrophoretically as typical high density lipoproteins and exhibited Stokes diameters in the 130-160 A range; apoA-I was the predominant protein. In addition to this polypeptide, fraction II contained small amounts of a supplementary protein (Mr approximately 51,000), exhibiting heparin-binding properties. In the light of results reported in the literature, we suggest that this latter protein could correspond to beta 2 glycoprotein I. The chemical composition of each fraction II closely resembled that of the corresponding fraction I, while their electrophoretic migrations appeared slightly slower and their Stokes diameters slightly larger (155-165 A). Apart from the presence of small amounts of apoA-I, two high Mr proteins (Mr approx. 560,000 and 300,000) were typical of the apolipoprotein moiety of fractions III. The lower Mr form was present as a trace component only in fraction III originating from plasma; its proportion increased in lymph fraction III so as to approximately match that of the higher Mr (i.e., 560,000) protein. In both plasma and lymph, fraction III was electrophoretically heterogeneous, exhibiting a doublet of bands with migration and Stokes diameters (250 A) typical of low density lipoprotein particles. However, no evidence for the presence of a particle resembling lipoprotein[a] in fraction III could be obtained. In lymph only, fraction III contained a supplementary population of lipoproteins with migration intermediary between those of conventional low and high density lipoproteins and with Stokes diameters in the 190-200 A range. Other specific features of lymph fraction III included a sevenfold increase in its triglyceride content (8.5 +/- 3.4% vs. 1.2 +/- 1.1% in the corresponding fraction from plasma), to the detriment of cholesteryl esters, and a higher proportion of protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753214 TI - Occurrence of isomeric dehydrocholesterols in human plasma. AB - Three isomeric dehydrocholesterols were found in plasma from healthy subjects and patients with abnormal production or metabolism of cholesterol. These chemically labile steroids were isolated by a mild liquid-solid extraction procedure using octadecylsilane-bonded silica as sorbent. Sterol-protein interactions were minimized by diluting plasma with aqueous isopropanol. The dehydrocholesterols were identified by high-performance liquid chromatography-ultraviolet spectroscopy and gas chromatography-mass spectrometry as cholesta-5,7-dien-3 beta ol (7-dehydrocholesterol), 5 alpha-cholesta-6,8(9)-dien-3 beta-ol (isodehydrocholesterol), and tentatively as cholesta-5,8(9)-dien-3 beta-ol. There was a strong positive correlation between plasma levels of the two former compounds, isodehydrocholesterol levels usually being about 1.4 times higher than those of 7-dehydrocholesterol. The median concentration of 7-dehydrocholesterol in plasma from healthy subjects was 52 ng/ml. Similar concentrations were found in colectomized patients (median concentration 47 ng/ml) and patients with extrahepatic cholestasis and alcoholic liver cirrhosis (median concentrations 79 and 67 ng/ml, respectively). Patients with ileal resection or under treatment with cholestyramine had elevated levels (median concentrations 142 and 160 ng/ml, respectively) whereas patients with primary biliary cirrhosis had subnormal levels (median concentration 26 ng/ml). The results are consistent with a positive correlation between levels of the dehydrocholesterols in plasma and the rate of cholesterol synthesis. The sterols were also analyzed in human skin and bile and the results indicate that the liver may be an important source of isodehydrocholesterol. PMID- 1753215 TI - Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. AB - The regulation of the expression of adipose-related genes, i.e., aP2, adipsin, and glycerophosphate dehydrogenase (GPDH) by growth hormone (GH) and polyamines, as well as the role of fatty acids, have been investigated in polyamine-dependent Ob1754 cells and Ob1771 preadipose cells. Growth hormone acts as an obligatory hormone for adipsin and GPDH gene expression but its presence is not required for the expression of the aP2 gene. In fully differentiated Ob1771 cells, impairment of fatty acid synthesis by glucose deprivation leads to an inhibition of the aP2 gene expression, whereas the expression of adipsin and GPDH genes remains unaffected. Supplementation of the culture medium with fatty acids prevents the decrease of aP2 gene expression, and this effect appears primarily due to an increase in the transcriptional level of aP2 gene. The induction of aP2 gene has been examined in early committed, lipid-free Ob1771 cells in which fatty acid synthesis is very low despite glucose supplementation. Long-chain fatty acids (greater than or equal to C12) are able to activate the aP2 gene. It is concluded that fatty acids or fatty acid metabolites activate the aP2 gene and subsequently modulate its expression. PMID- 1753216 TI - Regulation of adipose cell differentiation. II. Kinetics of induction of the aP2 gene by fatty acids and modulation by dexamethasone. AB - Fatty acids behave as activators of the aP2 gene expression in committed, lipid free, non-terminally differentiated Ob1771 cells. Like fatty acids, dexamethasone provokes a dose-dependent accumulation of aP2 mRNA. However, fatty acids and dexamethasone act through different mechanisms to activate the aP2 gene expression since i) fatty acids and dexamethasone act in a synergistic manner; ii) the effect of dexamethasone is rapid and transient (maximal effect after 8 h), whereas that of fatty acids is slower, and maintained as long as the inducer is present and is fully reversible upon fatty acid removal; iii) the induction of the aP2 gene expression by dexamethasone does not require ongoing protein synthesis, while the response to fatty acids is completely prevented by cycloheximide; and iv) the induction of the aP2 gene expression by fatty acids but not by dexamethasone is confined to preadipocyte cell lines. This suggests that the process of activation by fatty acids, rather than the expression of the aP2 gene, is unique to adipose cells. Besides their effects on the aP2 gene, fatty acids activate the expression of the acyl CoA synthetase gene which encodes another protein involved in fatty acid metabolism. Activation of both genes by fatty acids appears not to be mediated by the CCAAT enhancer binding protein, a nuclear factor reported as transactivator of the aP2 promoter activity, since the enhancer binding protein mRNA is not expressed under these conditions. PMID- 1753217 TI - Site-specific methionine sulfoxide formation is the structural basis of chromatographic heterogeneity of apolipoproteins A-I, C-II, and C-III. AB - ApoA-I and apoC-II are eluted in two isoforms and apoC-III2 is eluted in three isoforms by reversed phase high performance liquid chromatography (HPLC). The structural basis of these nongenetic heterogeneities was unravelled using HPLC of proteolytic peptides and time-of-flight secondary ion mass spectrometry (TOF SIMS). In apoA-I, the chromatographic microheterogeneity was caused by the formation of methionine sulfoxides (MetSO). However, only residues Met112 and Met148 were found oxidized, whereas Met86 was unaffected and also resistant towards artificial oxidation. To assess whether and to what extent amino acid substitutions in apoA-I might affect methionine sulfoxidation, the tryptic peptides of 13 different mutant apoA-I proteins from 24 heterozygous apoA-I variant carriers were analyzed by HPLC. In normal apoA-I, the ratios MetSO112/Met112 and MetSO148/Met148 were highly variable. By contrast, the relative ratio of oxidation of methionine residues 112 and 148 was constant. The amino acid changes Lys107----Met, Lys107----O, Glu139----Gly, Glu147----Val, and Pro165----Arg resulted in the preferential oxidation of Met112, and Asp103----Asn resulted in a preferential oxidation of Met148; whereas Pro3----Arg, Pro3----His, Pro4----Arg, Asp89----Glu, Ala158----Asp, Glu198----Lys, and Asp213----Gly had no impact. ApoC-II and apoC-III isoforms differed by the oxidation of the two methionine residues in these proteins. Whereas in apoC-II both methionine residues were oxidized in parallel, in apoC-III the two methionine residues differed in their susceptibility towards oxidation. We conclude that the formation of MetSO depends on the molecular microenvironment within a protein. PMID- 1753219 TI - Ontogeny of two vitamin A-metabolizing enzymes and two retinol-binding proteins present in the small intestine of the rat. AB - The patterns of expression of cellular retinol-binding protein (CRBP), cellular retinol-binding protein, type two [CRBP(II)], lecithin: retinol acyltransferase (LRAT), and microsomal retinal reductase were examined for rat small intestine during the perinatal period. CRBP was present (15 pmole per mg soluble protein) at the earliest time examined, the 16th day of gestation, declining by 70% by birth, maintained to adulthood. In contrast, CRBP(II) appeared 2-3 days before birth, rising to its highest level (500 pmole per mg soluble protein) by day 3 after birth, then declining by 50% during the late suckling period to the adult level. Immunohistochemistry revealed that CRBP(II) initially appeared in the epithelial cell layer in a patchy manner, resolving by birth into an even staining of all villus-associated enterocytes. In contrast, CRBP was evenly expressed in the epithelial cell layer at day 17/18 but was absent by birth. Intestinal LRAT activity increased rapidly in the 2 days prior to birth, then declined at weaning to the adult level. Microsomal retinal reductase was measurable in the intestine at birth, but not detected during the early suckling period, reappearing at day 21. Considerable increase was then observed coincident with weaning, when carotenes, from which retinal is derived, became an important source of vitamin A. The pattern of appearance of these elements appears to prepare the intestine for the necessary processing of vitamin A required after birth. PMID- 1753218 TI - Influence of total lipid concentration, bile salt:lecithin ratio, and cholesterol content on inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile. AB - We modified classic equilibrium dialysis methodology to correct for dialysant dilution and Donnan effects, and have systematically studied how variations in total lipid concentration, bile salt (taurocholate):lecithin (egg yolk) ratio, and cholesterol content influence inter-mixed micellar/vesicular (non-lecithin associated) concentrations (IMC) of bile salts (BS) in model bile. To simulate large volumes of dialysant, the total volume (1 ml) of model bile was exchanged nine times during dialysis. When equilibrium was reached, dialysate BS concentrations plateaued, and initial and final BS concentrations in the dialysant were identical. After corrections for Donnan effects, IMC values were appreciably lower than final dialysate BS concentrations. Quasielastic light scattering was used to validate these IMC values by demonstrating that lipid particle sizes and mean scattered light intensities did not vary when model biles were diluted with aqueous BS solutions of the appropriate IMC. Micelles and vesicles were separated from cholesterol-supersaturated model bile, utilizing high performance gel chromatography with an eluant containing the IMC. Upon rechromatography of micelles and vesicles using an identical IMC, there was no net transfer of lipid between micelles and vesicles. To simulate dilution during gel filtration, model biles were diluted with 10 mM Na cholate, the prevailing literature eluant, resulting in net transfer of lipid between micelles and vesicles, the direction of which depended upon total lipid concentration and BS/lecithin ratio. Using the present methodology, we demonstrated that inter mixed micellar/vesicular concentrations (IMC) values increased strongly (5 to 40 mM) with increases in both bile salt (BS):lecithin ratio and total lipid concentration, whereas variations in cholesterol content had no appreciable effects. For model biles with typical physiological biliary lipid compositions, IMC values exceeded the critical micellar concentration of the pure BS, implying that in cholesterol-supersaturated biles, simple BS micelles coexist with mixed BS/lecithin/cholesterol micelles and cholesterol/lecithin vesicles. We believe that this methodology allows the systematic evaluation of IMC values, with the ultimate aim of accurately separating micellar, vesicular, and potential other cholesterol-carrying particles from native bile. PMID- 1753220 TI - The tocsin sounds. PMID- 1753221 TI - Sovietization of American medicine. PMID- 1753222 TI - Primary care. A role for nurses. PMID- 1753223 TI - Symptomatic adult polycystic liver disease in a young woman. AB - Adult polycystic liver disease is an entity that is striking for the presence of extraordinary hepatomegaly. Very rarely do patients under 40 years of age experience problems and only a minority of middle-aged patients manifest symptoms due to organ compression or biliary tree obstruction. The clinical course is usually benign, and no specific therapy is required. The onset of right upper quadrant pain, back pain, and shortness of breath prompted evaluation of a 32 year-old woman with progressive hepatomegaly. CT scan revealed a massive cyst riddled liver with posterior displacement of the spleen, compression of the pancreas, and renal cysts. Prothrombin time, albumin, and liver enzyme values were normal except for a mildly elevated gamma-glutamyl transpeptidase. PMID- 1753224 TI - The aging population. A critical issue in medicine for the 21st century. AB - One critical issue facing medical science concerns the aging population. The number of individuals 65 years and older has increased during the past decade and likely will double by the year 2030, when the elderly will represent nearly 20% of the total population. This dramatic increase has numerous ramifications; health care is of utmost importance. Inherent in meeting the medical needs of these individuals is a fundamental understanding of the effects of aging on the functional integrity of numerous organ systems. In recognition of this problem, the Department of Pharmacology and Therapeutics at the University of South Florida College of Medicine has initiated a major effort focused on age-related research. The objectives are to elucidate fundamental biochemical, physiological, and pharmacological alterations that occur as a consequence of normal aging and to investigate the role of these perturbations on the manifestations of disease. Information gained from such studies will provide a rational approach in developing therapeutic strategies for the treatment of diseases affecting older citizens. This article presents a brief overview of four areas of research currently being pursued. These include aging and brain function, age-related alterations in drug metabolism, aging and smooth muscle function, and the effects of aging on the immune system. PMID- 1753225 TI - Orthostatic hypotension in the elderly. PMID- 1753226 TI - Under pressure. Soaring costs in health care will require some tough decisions. PMID- 1753227 TI - AIDS in Florida. The first decade. PMID- 1753228 TI - Infection control. AB - "Universal precautions" and "strict infection control procedures" have become health-care facility as well as household terms. However, not much time has been given to explaining the specifics of exactly what they are or how and when they should be applied. The purpose, therefore, of this article is to review these specifics for practicing physicians, regardless of their specialty. PMID- 1753229 TI - Legal considerations. Current Florida law. AB - Legislation enacted in 1991 requires physicians licensed under Chapters 458 or 459, Florida Statutes, to earn continuing medical education in the area of HIV and AIDS and specifies what should be covered in the program. The law no longer requires that certain information be imparted to the patient prior to testing for the human immunodeficiency virus. Information is presented on who can consent to testing, when consent is not required, pre- and post-testing requirements, confidentiality of patient records and possible disclosure and testing as a condition of treatment or admission. PMID- 1753230 TI - Management of HIV infection in adults. AB - The natural history of HIV infection continues to change with improved diagnostic and therapeutic modalities available to manage opportunistic infections and malignancies. Antiretroviral therapy with zidovudine and other investigational agents has improved the median survival of AIDS patients from 11 months in 1985 to 18-25 months at present. Most importantly, early intervention with zidovudine can delay onset of clinical illness in asymptomatic patients and progression to AIDS in symptomatic patients. A 500 mg/d dose has been found as effective as previously recommended doses of 1200-1500 mg/day. Lower doses decrease the incidence and severity of adverse effects and therapeutic benefit appears to be greatest in asymptomatic patients with CD4 lymphocyte counts less than 500/ul. Indications for zidovudine, therefore, have been expanded to include asymptomatic adults with CD4 lymphocyte counts less than 500/ul. Concerning early intervention with zidovudine, studies were not designed to measure survival or define the optimal timing of intervention based on immunologic status. In addition, long term benefits are not clearly defined, particularly since the drug seems to lose clinical effectiveness after approximately two years, probably due to emergence of resistant HIV strains. Adverse effects continue to occur even at low doses including headaches, nausea, anemia and neutropenia, myopathy and possible hepatitis. Nevertheless, the overall clinical benefit seems to be greatest, albeit temporary, in asymptomatic patients. The optimal dosage appears to be 500 600 mg/d; however, this may not be sufficient for infection in the central nervous system. PMID- 1753231 TI - Epidemiology of AIDS in Florida. AB - Florida is third in the nation in the cumulative number of AIDS cases. The epidemic in the state has grown steadily since 1981, clustering initially in metropolitan South Florida but dispersing to other urban and nonurban areas. Heterosexually transmitted AIDS is fast increasing and is more than twice as common in Florida than the United States; however, homosexual/bisexual men and intravenous drug-using men and women continue to represent the majority of new cases. Special serologic studies of the prevalence of HIV infection provide a timely view of the dynamics and characteristics of the epidemic in various segments of the state's population. Data from a large, ongoing serosurvey suggest that about one in every 220 childbearing women is HIV-infected, a finding consistent with Florida's rank of second nationally in the number of pediatric AIDS cases. PMID- 1753232 TI - Pediatric HIV infection. An update. AB - Human immunodeficiency virus infection is a leading cause of immunodeficiency in children. The epidemic in children parallels that in women since most infected women are in the child-bearing age groups. The risk of vertical transmission of HIV from an infected mother to her infant ranges from 13% to 39%. Diagnosis of infection in the infant is complicated by the passive transfer of antibody across the placenta, making the use of standard serologic tests to confirm infection difficult. In children less than 15 months of age, a positive p24 core antigen test, a positive viral culture or AIDS defining criteria with immune abnormalities are required for diagnosis. HIV infection in children is chronic and multisystem characterized by immunologic and clinical deterioration with a higher incidence of serious bacterial infections, neurologic disease, and lymphoid interstitial pneumonitis. The cornerstones of management include close medical follow-up, good nutrition, and prompt diagnosis and treatment of infections. Certain children will benefit from therapeutic modalities such as Pneumocystis carinii pneumonia prophylaxis and/or intravenous gamma globulin. The antiretroviral drugs have improved the quality of life and increased survival. Several newer antiviral agents are presently in clinical trials. PMID- 1753233 TI - Pathogenesis and natural history of HIV infection. AB - Acquired immune deficiency syndrome (AIDS) is caused by infection with the human immunodeficiency virus (HIV), a human retrovirus. The virus infects cells of the immune system by attachment of a glycoprotein viral envelope (gp 120) to a molecule expressed on human helper T cells called CD4. The fusion of the virus envelope protein to its specific receptor allows HIV to penetrate the T cell. Once inside the cell viral RNA is transcribed into double-stranded DNA by an enzyme unique to retroviruses, reverse transcriptase. The double-stranded, proviral DNA travels to the nucleus of the cell and is integrated into the infected cell's chromosomal DNA where it may remain latent for years. As a result of triggers that are poorly understood, viral replication becomes activated and proviral DNA is transcribed back into genomic RNA and RNA that is translated into viral proteins, both of which are packaged and bud from the infected T cell as infectious virus. The viral life cycle orchestrates the natural history of clinical HIV infection. Three to four weeks following exposure to HIV there is a phase of rapid viral replication, high levels of plasma viremia, and development of a "flue like" illness. Four to six weeks after exposure, during this stage of acute infection, antibodies to HIV core (p24) and envelope (gp 160, gp 120, gp41) proteins appear. Six to eight weeks after exposure symptoms disappear and plasma viremia subsides, presumably due to clearance by the immune system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753234 TI - Medical utopia. PMID- 1753235 TI - Inappropriate testing. PMID- 1753236 TI - Age-associated neurological diseases. PMID- 1753237 TI - Diagnosis, assessment and treatment of age-associated memory impairment. AB - We have reviewed diagnostic criteria and assessment procedures for AAMI, as well as pharmacologic and behavioral treatments for this condition. This research gives reason to hope that an important behavioral deficit associated with aging may be modified through drug and behavioral treatment. PMID- 1753238 TI - Essential tremor: functional disability vs. subjective impairment. AB - 78 patients with essential tremor (ET) were investigated to uncover correlation and discrepancies between functional (motor) disabilities and subjective impairment. Various self-rating scales (Zung, v. Zerssen etc.) were used for the assessment of the latter: 2/5 of the patients rated themselves as severely impaired; 1/3 was depressive. Patients who showed nearly the same functional (motor) disability felt very differently subjectively impaired. Semiquantitative clinical scores of action tremor correlated best with the subjective impairment in activities of daily living. Objective measurements of motor disability were performed with the "Motorische Leistungsserie nach Schoppe" (motor performance test) and showed good correlation to the subjective impairment in simple tasks of every day life, such as drinking from a glass, eating soup, and writing. Asking for the subjective impairment in these tasks allows to estimate the objective disability correctly. This may be of value in long-term studies of essential tremor. PMID- 1753239 TI - Sympathetic vascular function in patients with central dysautonomia. AB - This study used digital photoplethysmography (d-FPG) to investigate alterations in skin blood flow after exposure to cold as well as the post-prandial blood pressure pattern to assess how the sympathetic branch of autonomic nervous system (ANS) functioned in 31 patients with cerebral dysautonomia and in 27 healthy controls. d-FPG was carried out on all ten fingers in basal conditions and after exposure to ice-cold water (4-5 degrees C). Amplitude, crest time and inclination time were used to calculate the alterations induced by the cold pressor test. After a standard lunch blood pressure was monitored every 20 minutes using a fully automatic non-invasive sphygmanometer. Unlike the controls the amplitude of the photoplethysmographic wave increased in all patients except 2; crest time and inclination time decreased in all except 3; post-prandial diastolic and systolic blood pressure levels fell markedly in all but 3. Blood vessel smooth muscle tone is disturbed in patients with ANS failure because dysautonomia may permit the action of vasodilating substances to predominate. The post-prandial blood pressure pattern and the d-FPG used in conjunction with a cold pressor test are useful tools in the non-invasive investigation of ANS function. PMID- 1753240 TI - Epidemiology and out-patient care in Parkinson's disease--results from a pilot study in northern Germany (Schleswig-Holstein). AB - An attempt was made to estimate prevalence on Parkinsonism using consultation rates in physicians' practices in a two-step, one-phasic pilot study in a rural urban area of Northern Germany. Though participation of physicians was low, reported rates for Parkinsonian patients (183/100,000) were in the range yielded in comparable areas, but by different methodology. Only 64% of a large subsample of patients used L-Dopa preparations for therapy. Confirming previous results the objective records of doctors and the subjective notices of patients regarding disease state showed considerable differences in several important items. PMID- 1753241 TI - Effects of treatment with trihexyphenidyl on cognitive function in early Parkinson's disease. AB - 13 patients with PD of recent onset underwent a series of neuropsychological tests for frontal lobe associated functions (Sternberg paradigm, WCST, CVLT) before and during treatment with Artane. Test results at baseline were not significantly different from those of an age-matched control group (n = 13). Retesting after a mean of 2 weeks' treatment with trihexyphenidyl revealed only slight impairment in CVLT while performance on the other tests remained unchanged. PMID- 1753242 TI - Positron emission tomography in the differential diagnosis of organic dementias. AB - At present, PET is the only technology affording the quantitative, three dimensional imaging of various aspects of brain function. Since function and metabolism are coupled, and since glucose is the dominant substrate of the brain's energy metabolism, studies of glucose metabolism by PET of 2(18F)-fluoro 2-deoxy-D-glucose (FDG) are widely applied for investigating the participation of various brain systems in simple or complex stimulations and tasks. In focal or diffuse disorders of the brain, functional impairment of affected or inactivated brain regions is a reproducible finding. While glucose metabolism is decreased slightly with age in a regionally different degree, in most types of dementia severe changes of glucose metabolism are observed. Degenerative dementia of the Alzheimer type is characterized by a metabolic disturbance most prominent in the parieto-occipito-temporal association cortex and later in the frontal lobe, while primary cortical areas, basal ganglia, thalamus, and cerebellum are not affected. By this typical pattern Alzheimer disease can be differentiated from other dementia syndromes, as e.g., Pick's disease (with the metabolic depression most prominent in the frontal and temporal lobe), multi infarct dementia (with multiple focal metabolic defects), and Huntington's chorea (with metabolic disturbance in the neostriatum). In demented patients PET studies can also be applied to the quantification of treatment effects on disturbed metabolism. PMID- 1753243 TI - MRI in basal ganglia diseases. AB - 76 patients suffering from different basal ganglia diseases (28 cases with M. Parkinson, secondary parkinsonism and Parkinson diseases; 5 cases with Chorea Huntington; 5 cases with Fahr disease and 38 cases with M. Wilson) MRI featured 2 characteristical patterns: 1. abnormal deposition of minerals, 2. focal atrophies of involved organs. Thus MRI provides with informations about: 1. differential diagnosis in clinically misleading courses, 2. stage and, as a consequence, prognosis of some diseases, 3. biochemical processes of diseases in vivo. PMID- 1753244 TI - Extrapyramidal disturbances after cyanide poisoning (first MRT-investigation of the brain). AB - A 29 year old student of chemistry took 50 ml of a 1% potassium cyanide solution (500 mg) in attempted suicide. He became comatose, mydriatic and was admitted to hospital in an apneic state. He woke up after seven hours and developed Parkinsonism in the following weeks. This regressed slowly in the second month after the poisoning apart from dysarthria, bradykinesia of the upper limbs and very brisk monosynaptic reflexes. Three weeks after the intoxication, CCT was largely normal, and there was CSF-dense hypodensity in both putamina after five months. Sharply delimited signal elevation in T2 corresponding to the two putamina was detected in the MRI eight weeks and five months after ingestion of the poison. PMID- 1753245 TI - Stroke: evaluation of long-term rehabilitation effects. AB - A planned prospective documentation of the course of rehabilitation of 303 stroke patients was undertaken using the Bathel-Index as a measure of basic everyday functions and the Guttman-Scale as a measure of complex activities of daily living. These were determined at the beginning of rehabilitation, after an average of 7 weeks of in-patient treatment and one year following the stroke. Four patterns in the course of rehabilitation could be differentiated. The causes of the differing functional results were investigated. Besides a positive spontaneous progress of the underlaying disease with an early reparation of the neurological deficits it is the premorbid status, the overprotection of the physically disabled and the determinative cognitive and mental functions that decide the long term fate of stroke patients. PMID- 1753246 TI - Medical educational and functional determinants of employment after stroke. AB - To evaluate the medical educational and functional determinants of employment after stroke a total of 204 Patients were assessed for functional changes during rehabilitation and after one year. Additionally the educational and social background of each patient was documented. One year after discharge from the rehabilitation unit 11.3% of the patients worked full-time and 2.7% part time. Another 14.7% had the decision pension versus employment still pending and 0.5% were classified as unemployed. 70.8% received regular retirement plan payments or disability pensions. Generally a similar level of functional capabilities can be observed after one year for working and non-working patients except for manual dexterity. Early admission to rehabilitation (within the first 12 weeks) favours return to work. A high school degree qualifying for university entrance and a well paid and better qualified profession as well are correlated with a higher percentage of patients regaining their employment. An other determining factor of employment after CVA is the physical requirement of the former work. Most of the working patients (92%) had been either transferred onto a job suited for an handicapped people or their work plan had been restructured accordingly. PMID- 1753247 TI - The spectrum of subcortical lesions in MRI, sensitivity and specificity. AB - Subcortical foci of increased signal intensity are frequently identified on MRI in the elderly. The lesions are compatible with various pathologic processes and MRI can only provide supportive data for a suspected diagnosis. Without the patient's clinical history the radiologist is not able to differentiate between real pathologic lesions and physiologic aging processes. The high sensitivity of MRI in detecting white matter lesions and the lack of specificity recommends an excellent teamwork between clinicians and radiologists. PMID- 1753248 TI - Cytoskeleton pathology in Alzheimer's disease and related disorders. AB - The reported findings suggest that ubiquitination of pathological proteinaceous intracytoplasmic inclusions is not at all specific of AD. On the contrary it appears to be a general biochemical marker for disorders in the degradation of a variety of cytoskeletal and other cytoplasmic proteins. The pattern of affected cytoskeletal components is not specific of AD/SDAT tangles. Tau definitely is present also in PSP tangles and possibly in Pick bodies but not in Lewy bodies. Therefore it has to be considered that the intracytoplasmic accumulation of cytoskeletal protein/ubiquitin complexes in itself is a rather unspecific cellular reaction pattern, possibly a secondary reaction to cell injury of many types, especially, however, of neuronal aging. Nevertheless, the manifestation of NFT in an excessive quantity, intensity, and dynamics with severe concomitant lesions as in AD/SDAT undoubtedly is a true pathological and in this sense a disease-specific change. PMID- 1753249 TI - Morphometry of the corpus callosum in normal aging and Alzheimer's disease. AB - Changes of the human corpus callosum in normal aging and Alzheimer's disease were analysed by means of morphometry. A standardized computerized evaluation program was implemented allowing objective, quantitative and reproducible data. The various parts of the corpus callosum showed a different pattern of changes in normal aging as compared to Alzheimer's disease. In conclusion, in normal aging affects mostly the front-temporal interhemispheric fiber systems, whereas in Alzheimer's disease the parietotemporal commissural fibers are altered. PMID- 1753250 TI - Clinical and epidemiological aspects of dementia in the elderly. AB - Dementia of the Alzheimer's type (DAT) is the most significant disease of the aging brain. Descriptive epidemiology of DAT found a constant doubling of prevalence rates every 5 years. Analytic epidemiology so far failed to reliably detect risk factors for DAT other than age. This might depend on the difficulties encountered in the clinical diagnosis and differential diagnosis of dementia in the elderly, which are discussed with special reference to 1) the definition of dementia, to 2) the grading of severity of dementia, to 3) the differentiation between dementia and depression, and to 4) the differentiation between multi infarct dementia and DAT. PMID- 1753251 TI - Multi-infarct dementia. AB - Clinicians have long recognized that dementia is a common symptom among the elderly. The diagnosis of dementia requires us to document the individual's current level of mental functioning and some higher level of intellectual function in the past. The recognition of early or mild cases is specially difficult. Out of epidemiological studies it has been shown that the incidence for multi-infarct dementia (MID) increases with age and is slightly higher among men. PMID- 1753252 TI - Early diagnosis of Alzheimer dementia? AB - The main problems in early diagnosis of Alzheimer dementia (AD) are: 1. The differentiation between normal aging and AD i.e. difficulties in the assessment of cognitive disturbances in the healthy elderly and in early demented subjects. 2. Interference with other dementia syndromes. 3. Lack of information in the population and among physicians about the different causes and courses of dementia syndromes. The first two aspects are discussed in this paper. PMID- 1753253 TI - Galanthamine treatment in Alzheimer's disease. AB - 18 patients who had fulfilled the NINCDS-ADRDA criteria for "possible AD" took part in a clinical study to evaluate the effect of the cholinesterase inhibitor Galanthamine, 30 mg/day. Neuropsychological und social parameters were rated. This open clinical pilot-study showed no statistic significant change in neuropsychological test-results. However after 1 year treatment 6 patients are still taking the drug. According to their care-persons there was a positive changes in competence of everyday-routine and/or in the emotional situation. PMID- 1753255 TI - Pattern electroretinogram and luminance electroretinogram in Alzheimer's disease. AB - Visual symptoms are often among the first complaints of patients suffering from Alzheimer's disease and several studies showed a delay in flash visual evoked potentials. Hinton et al. (1986) described optic nerve degenerations in patients with Alzheimer's disease and Sadun published a dropout of retinal ganglion cells that range from 30% to 60%. The reduction of neurotransmitters, especially of acetylcholine, found in the brain might also occur in the retina. Therefore we examined the retinal functions of patients suffering from Alzheimer's disease. In eight patients the pattern-electroretinograms and the scotopic and photopic luminance-electroretinograms were recorded and compared to an age-matched control group. We could not find any abnormalities in the pattern- and the luminance electroretinograms of patients with Alzheimer's disease. Although cholinergic cells have been found in the retina, our results did not reveal an involvement of retinal functions in Morbus Alzheimer. PMID- 1753254 TI - Physiology of short-term verbal memory. AB - These studies document a series of brain events accompanying short-term memory functions. For auditory verbal material the sequence involves at least two different sites within auditory cortex subserving sensory and cognitive processes of memorization. During the scanning of the short-term store structures within the medial temporal lobes, presumably the hippocampus, are active. There is an inconsistency between these results and the clinical observations of the need for an intact dominant parietal lobe for auditory short-term memory to function normally. Magnetic recordings showed no focal dipolar source of activity in the parietal lobe during any aspect of auditory short-term memory. The discrepancy could be accounted for by considering the parietal lobe lesion as "disconnecting" the lateral temporal cortex from the deep medial hippocampal structures thereby impeding auditory short-term functions (Geschwind, 1965). These studies show that the physiological analysis of brain events in the msec range can provide information about relatively complex cognitive processes underlying short-term memory. The magnetic and electrical recording methods provide a noninvasive way to study human brain functions involved in cognition that can then be correlated with behavioral measures of specific cognitive activities. PMID- 1753256 TI - Memory dysfunction in Parkinson patients: an analysis of verbal learning processes. AB - The German version of the California verbal learning test (Munchner Gedachtnis Test) was administered to compare memory functions of 45 Parkinson patients and 32 healthy controls. Although the Parkinson patients were within their age norm in their performance on standard intelligence and memory tests, a significant pattern of impaired learning was observed with the MGT. While learning capacity showed a linear increase, it was altogether lower than that of healthy normals. Parkinson patients have difficulty organizing new material and applying useful strategies. When offered useful cues, they can apply these for a while, but soon loose these strategies again. They are more irritated by distractors than healthy people. Once material is learned and stored, it hampers the learning of new material. Also, new information disturbs the reproduction of formerly acquired information. PMID- 1753257 TI - Does the absence of clinical expression of choreoathetosis, despite severe striatal atrophy, correlate with plasticity of neuropeptide synthesis? AB - Neuropeptide and neurotransmitter plasticity has been demonstrated in the central nervous system. Modifications of their synthesis occur following receptor blockade or deafferentiation by surgical lesions. This concept should provid answers to some remaining open questions in human pathology especially in degenerative diseases of the basal ganglia. In a severely atrophied striatum we observed a selective increase in the number of detectable striatal substance P and met-enkephalin neurones which exhibited a striking increase in the intensity of labelling. This increase, instead of the well established reduction of substance P and enkephalins in the atrophied striatum of Huntington's disease, could explain the absence of choreoathetosis which was replaced by rigidity and bradykinesia in the patient. The absence of choreoathetosis, despite severe striatal atrophy, is described in several basal ganglia diseases and could also be related to neurotransmitter or neuropeptide plasticity rather than due to the primary lesion. PMID- 1753258 TI - Pharmacoepidemiology: a health imperative. PMID- 1753259 TI - The importance of models in the assessment of synergy. PMID- 1753260 TI - Prevalence of iron deficiency and iron overload in the adult Icelandic population. AB - The aim of this cross-sectional study was to estimate the prevalence of iron deficiency and overload in the adult population in Iceland, a developed Scandinavian country. The study population consisted of 4240 individuals aged 25 74 years randomly selected from the national roster. Basic hematological, S-iron, S-total iron binding capacity (TIBC), and S-ferritin measurements were obtained on 2588 individuals (61.0%). The results indicated unusually large iron stores in the adult Icelandic population and significantly larger iron stores in the rural compared to the urban population. Iron deficiency was rare except in urban premenopausal women, where 1 in 4 showed evidence of iron deficiency and 3.2% had iron deficiency anemia. Seven patients with hereditary hemochromatosis were identified from a subgroup of 1887 subjects, resulting in a prevalence of 0.37%. Two of the hereditary hemochromatosis patients had been gastrectomized. Measures to improve the iron balance in urban premenopausal women cannot therefore include increased iron fortification of food but must be more directed towards the target group. PMID- 1753261 TI - Epidemiological use of drug prescriptions as markers of disease frequency: an Italian experience. AB - All Italian citizens are covered by the National Health Service (NHS) and medical records of individual drug prescriptions are routinely collected and processed. A procedure entitled EPIFAR has been developed which, on the basis of a computer routine, makes it possible to trace back the prescription history of each individual included in the NHS. The validity of information gathered through the EPIFAR procedure to provide estimates of tuberculosis (TB) prevalence has been evaluated. A comparison with routine surveillance data has been made. The EPIFAR procedure identified a total figure of TB patients seven times higher than that from official notifications. A sample survey was conducted among the prescribing physicians in order to quantify the proportion of TB cases among subjects receiving prescriptions of anti-TB drugs. According to general practitioner recall 66.4% of the patients were treated because of TB diagnosis, TB prophylaxis and TB relapse. PMID- 1753262 TI - The Toronto Breast Self-Examination Instrument (TBSEI): its development and reliability and validity data. AB - The Toronto Breast Self-Examination Instrument (TBSEI) was developed out of the need for a self-administered survey that is reliable and valid. This article describes the development of the TBSEI, its dimensions, and reliability and validity data to support its continued use. To analyze the reliability and validity properties of the three TBSEI scales, we surveyed 729 Toronto, Ontario women. The TBSEI was found to have good face and content validity, internal consistency reliability (0.91, 0.69, 0.85), and test-retest reliability (0.89). Age norms for each of the three scales are also provided. These results are consistent with previous research findings in breast cancer and breast self examination research. PMID- 1753263 TI - Reliability and physiologic correlates of the Harvard Alumni Activity Survey in a general population. AB - The reliability of the Harvard Alumni Activity Survey (HAAS) and its association with physiologic measures was assessed in a large sample of men and women aged 25 65 years residing in the Boston metropolitan area in 1987. Reliability was estimated by comparing HAAS energy expenditure reports (kcal/week) from two separate interviews conducted 7-12 weeks apart. The test-retest reliability coefficient was 0.58 for the entire sample, but was considerably higher (r = 0.69) for those whose activity patterns had not changed from one interview to the next. HAAS self-reports were compared to two physiologic measures known to be affected by physical activity: high density lipoprotein cholesterol (HDLC) and body mass index (BMI). The natural logarithm of weekly HAAS expenditures was positively correlated with HDLC (r = 0.14, p less than 0.01) and negatively correlated with BMI (r = 0.13, p less than 0.01) for all respondents. These statistically significant associations persisted when adjusted for other covariates influencing physiologic status. The reliability coefficients and physiologic correlations for the HAAS in this sample are comparable to those reported for physical activity instruments requiring more intensive data collection and scoring procedures. PMID- 1753264 TI - The cure model and time confounded risk in the analysis of survival and other timed events. AB - The use of the Kaplan-Meier estimator for the analysis and testing of cure model data is discussed and results are compared with the more commonly used logrank test. The Kaplan-Meier estimator is particularly appropriate for describing the shape of the underlying survival distribution of data from bone marrow transplantation but is also relevant for different types of timed events data from other chronic diseases. The estimate of the event-free fraction by the product limit, may have a bias depending on the extent of follow-up, the parameters of the model, and confounding by competing risk events. The test based on the product limit has appropriate size and is more powerful as long as follow up is sufficient to minimize the bias. On the other hand, the logrank test, which is optimal for testing differences in time-to-event curves under proportional hazard assumptions, may be inappropriate and misleading for evaluating the difference in event-free fractions under the cure model. PMID- 1753265 TI - 27-year mortality in the Western Collaborative Group Study: construction of risk groups by recursive partitioning. AB - The relationship of selected biological and behavioral characteristics measured at baseline examination to 27-year mortality due to coronary heart disease (CHD), cancers of all sites, and total mortality in the 3154 men that form the Western Collaborative Group Study was investigated using tree-structured survival analysis or recursive partitioning (RP). Intake (1960-61) characteristics included in the present analyses were age, serum cholesterol, systolic blood pressure (SBP), cigarette smoking, body mass index (BMI), Type A/B behavior, and behavioral hostility. Tree-structured survival analysis for CHD mortality partitioned the cohort into six groups and identified five groups with distinct survival experience. Exceptionally high CHD mortality rates (17.3 and 14.6 per thousand) were experienced by 89 older men with elevated hostility ratings and SBP less than or equal to 150, and 238 men whose initial SBP was greater than 150 mmHg. Younger men (age less than or equal to 48) with SBP less than or equal to 150 and with serum cholesterol levels greater than 227 had a death rate of 4.8 per thousand, compared with a rate of 1.7 in similar men with lower cholesterol levels. Applied to 27-year cancer mortality, the RP algorithm partitioned the cohort into four distinct survival groups. Younger (age less than 45) Type B men had superior survival compared with Type A men of similar ages, and the proportion of ever cigarette smokers in these two groups was not statistically different. The results obtained by tree-structured survival analyses were compared with results obtained by Cox regression survival analyses. PMID- 1753266 TI - A longitudinal evaluation of drug use in an ambulatory elderly population. AB - Participants in a geriatric health screening program were studied longitudinally to determine the patterns of drug use over a 10 year period. There were 314 (34.0%) men and 610 (66.0%) women who completed 10 yearly health screening evaluations. The mean number of prescribed and non-prescribed drugs used per participant increased from 2.90 in 1978-79 to 4.08 in 1987-88 (p less than 0.0001). There was no significant difference between men and women in the rate of increased drug use. There was no significant increase in the mean number of drug ingredients per participant used over the 10 year period. The most frequently reported therapeutic categories for 1978-79 were antihypertensives, analgesic antipyretics, antirheumatics, multiple vitamins, cathartics and vitamin E, which represented 10.2, 7.2, 6.5, 4.9, 4.8 and 3.8% of all categories used. There was a decline in all of these categories between interval 1 and 10. Increased use of drugs, particularly prescribed medications, by the elderly population may present problems of adverse drug reactions, drug interactions and medication compliance in the future. Changing patterns of drug use may have resulted, in part, from introduction of new therapeutic classes and from new treatment concepts over the 10 year study period. PMID- 1753267 TI - Appropriate reductions in compliance among well-controlled hypertensive patients. AB - Physicians have traditionally viewed partial compliance with medications as a concern only in hypertensive patients whose blood pressure (BP) is poorly controlled. However, partial compliance also occurs in patients whose BP has become normal on medications; in them, reduced compliance may indicate that they have been prescribed more medication than they need. During enrollment for a study of medication reduction in hypertensive patients, we identified 118 male veterans who were eligible for the study because their diastolic BP had been less than 95 mmHg for more than 6 months. Fifty-nine of these patients (50.0%) agreed to participate in the study, of whom 71% successfully reduced or stopped ("stepped down") one or more of their antihypertensive drugs over a 1-year period. The 59 patients who did not enroll continued to receive routine care for hypertension in the clinic without intensive efforts at stepdown. Nevertheless, 24% of these patients reduced or stopped at least one medication over the same time period. In the year prior to the study, 29 of the 118 eligible patients (24.6%) had obtained less than 80% of their medications, measured by pharmacy refill records. Compliance in obtaining antihypertensive medications prior to the study was lower among eligible patients who stepped down medications during the study year (90.4% +/- 18.7%) than in those who did not (102.1% +/- 26.1%, p = 0.006). After adjustment for other predictors of stepdown (number of medications, duration of clinic enrollment, and pre-reduction systolic BP), each 10% increase in compliance among all eligible patients was associated with a reduction in the odds ratio for successful stepdown of 0.8 (95% CI 0.5-1.0, p = 0.01). We conclude that many well-controlled hypertensives appropriately obtain less medications than they are prescribed. Such patients should be considered for reduction of antihypertensive drugs. PMID- 1753268 TI - Statistical significance and fragility criteria for assessing a difference of two proportions. AB - This paper compares the traditional methods of statistical inference on the data from biomedical studies with a proposed index of fragility in the results. In general, for any given study there are 8 possible combinations of conclusions regarding statistical significance, quantitative significance and fragility. The 8 possibilities are considered in turn with respect to how studies in each group might be interpreted. Numerical examples show that not all 8 possibilities need be attainable with a given study design, and that the relative likelihood of them occurring can vary widely. It is concluded that the fragility index may be a useful adjunct to conventional statistical inference, with certain intuitive appeal, but that more empirical experience is needed with the fragility method. PMID- 1753269 TI - Mass screening for rectal neoplasm in Jiashan County, China. AB - Jiashan county is a rural area in China with very high incidence and mortality rates of colorectal cancer. From 1980 to 1984, we conducted a mass screening for rectal neoplasm in the 11 people's communes in this county. Of the 72,879 individuals who were eligible for screening, 60,496 participated, representing an overall participation rate of 83.0%. Both the fecal occult blood (OB) test and rectoscopy were performed on 47,560 of the participants, and rectoscopy only was performed on the remaining 12,936 individuals. From the mass screening, 15 rectal cancers, 3 carcinoids, 899 polyps, 98 ulcers, and 7 inflammatory tumors were detected, a total of 1022 cases. Eight of the 15 detected cases of rectal cancer were in Dukes' stage A. We did not find any evidence for an association between schistosomiasis and colorectal cancer. Results from the OB test were found to have a negative correlation with results from rectoscopy (odds ratio = 0.8, 95% CI = 0.6, 1.1). The OB test had a high false positive rate of 32.7%, and a poor positive predictive value of 3.5%. Both its positive and negative predictive powers were below 1.0, in other words, its positive likelihood ratio was below 1.0 and negative likelihood ratio was above 1.0, indicating that the OB test is not informative and has a poor predictive accuracy for rectal neoplasm. In addition, there were a number of practical problems concerning the use of the OB test for mass screening in the rural community.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753270 TI - Laboratory data predicts survival post hospitalization. AB - From a database of 93,077 in-patient admissions, patients assigned to catastrophic, very severe, moderately severe, and average 30-day mortality risk categories (as defined in Medicare Hospital Mortality Information, 1989 release, from the Health Care Financing Administration (HCFA] were selected for study. These admissions account for 30% of all admissions, but 70% of all deaths up to 1 year post admission. To determine whether laboratory information adds to the predictive power of the information used by HCFA, we compare the performance of 1 year survival predictors (Cox model) that use only diagnostic, demographic, and comorbidity information, with the performance of predictors that also include laboratory information. Using a separate set of patients not used for model definition, we find that laboratory data contain significant prognostic information independent of that already available in non-laboratory data. In HCFA's catastrophic disorders for example, non-laboratory information reduces the average risk of predicting a wrong outcome by 17% relative to considering only catastrophic group membership, and adding laboratory data reduces this risk by a further 21%. These improvements result primarily from considering the outcomes of a small set of routine laboratory tests (maximum BUN, AST, and WBC, and minimum CO2, hematocrit, and sodium). PMID- 1753271 TI - Smoking characteristics and inhalation biochemistry in the Scottish population. AB - Data from a cross-sectional random population sample of 10,359 middle-aged Scottish men and women are used to investigate the relationships between self reported tobacco consumption and three biochemical markers of tobacco inhalation: expired air carbon monoxide (CO), serum thiocyanate and serum cotinine. These data represent one of the largest samples of these biochemical markers yet analysed. The results show that, for each sex, the biochemical markers are highly correlated for smokers and for the entire sample of mixed smokers and non smokers. CO is the preferred biochemical marker, in such groups, because it is the cheapest, is non-invasive and gives virtually instantaneous results. Self reported daily cigarette consumption also correlates well with each of these biochemical markers, and so it appears that people are, in the context of population studies, mainly truthful about their smoking. The relationships with self-reported cigarette consumption are curvilinear with apparent levelling out of the gradient at around 25 cigarettes/day for cotinine and thiocyanate and at greater than 40 cigarettes/day for CO. Sex differences are small, although thiocyanate is generally higher and cotinine generally lower in women with the same self-reported cigarette consumption as men. Amongst non-smokers, only cotinine is able to discriminate between self-reported levels of exposure to passive smoking. CO and thiocyanate are not suitable for measuring low levels of smoke inhalation, such as found in passive smokers. PMID- 1753272 TI - The drinking, passive smoking, smoking deception and serum cotinine in the Scottish Heart Health Study. AB - Following a recent claim that the use of cotinine in body fluids, to assess passive smoking and smoking "deception", was confounded by metabolic individuality, and by non-tobacco sources of dietary nicotine, particularly tea, data were examined from a large cross-sectional survey in a tea-drinking population. In 3383 men and women aged 40-59 years from the Scottish Heart Health Study, defined as non-smokers, both by self-report and by low thiocyanate and expired air carbon monoxide levels, serum cotinine showed minimal association with self-reported daily average tea consumption. However, there was a strong correlation between degree of self-reported passive tobacco smoke exposure and median serum cotinine level. In the same survey, serum cotinine in 4144 self reported non-smokers and in 3326 smokers showed entirely different distributions, but the same range, suggesting heavy nicotine intake in some "non-smokers". These analyses confirm that cotinine levels in true non-smokers reflect far more the nicotine in inhaled ambient tobacco smoke than they do nicotine in tea. Some smoking "deceivers" have the same degree of exposure to nicotine as heavy smokers. Despite individual variability, the claim of confounding is poorly supported, and cotinine is confirmed as an indicator both of passive smoking and of smoking deception. PMID- 1753273 TI - Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat. AB - 1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) of spinal neurons with input from the knee and its modulation during an acute inflammation of this joint. TDI of spinal neurons with articular input was assessed by applying reversible cold blocks to the lower thoracic cord. The amount of descending inhibition was estimated from the induction and/or increase of resting discharges and of the responses to mechanical stimuli to the knee and other structures during the transitory and reversible blocks. In each experiment one or a few neurons were investigated while the joint was in normal condition [altogether 15 nociceptive-specific (NS) and 6 wide-dynamic-range (WDR) neurons]. One of the neurons was then selected for long-term recordings during which an acute inflammation in the knee was induced by the intra-articular injection of kaolin and carrageenan. Before and during developing arthritis, cold blocks were applied to examine whether the amount of TDI would change during the inflammatory process. 2. The neurons with input from the normal knee were under TDI because application of the cold block induced or increased resting discharges and the responses to noxious compression of the knee and the adjacent thigh and lower leg. In 10 of 15 NS neurons, the response threshold was lowered into the innocuous range. In 9 of 17 cells tested, the excitatory receptive field expanded to the ipsilateral paw, and 4 neurons became inhibited by paw compression. Seven of 18 neurons tested revealed inhibitory receptive fields on the contralateral leg during cold block. The neurons were located in laminae IV-VII. 3. Fourteen neurons were continuously monitored during development of inflammation, and changes in the effectiveness of TDI were assessed by blocking the cord before and during the development of arthritis. In most neurons baseline resting activity in the intact state of the cord increased while the arthritis developed. This inflammation-evoked enhancement of resting discharges was more pronounced during periods of spinalization. Consequently, the differences between the resting discharges in the cold-blocked and the intact state were progressively enhanced in arthritis. 4. After induction of arthritis, the responses to compression of the knee joint increased in the intact state as well as during cold blocks. In 11 of 14 neurons, the differences between the responses in the spinal and intact state were progressively enlarged during the development of inflammation. A similar result was obtained for flexion of the injected knee.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753274 TI - Electrophysiological study of spinothalamic inputs to ventrolateral and adjacent thalamic nuclei of the cat. AB - 1. Extracellular and intracellular methods were used to record from fibers and neurons in the ventral lateral (VL) and adjacent nuclei of the cat thalamus. The receptive fields of the recorded units were analyzed and the units tested for inputs from the medial lemniscus (ML) and spinothalamic tract (STT) by electrical stimulation of the dorsal columns (DC) and ventrolateral funiculus (VLF) at the C2-3 spinal level. 2. Thirty-eight STT fibers were isolated in the thalamus. Their conduction velocities ranged from 15 to 75 m/s (mode 36 m/s). Adequate stimuli were found for 23 of these fibers. Seventeen were low-threshold (LT), 3 were wide-dynamic-range (WDR), and 3 were high-threshold (HT) units. 3. Five STT fibers were intra-axonally injected. Three were sufficiently well filled for analysis of their terminal fields. An intermediate-velocity STT fiber (conduction velocity 38 m/s) had a 4.3-microns axon and a single large terminal field in the central lateral nucleus (CL). The other two STT fibers were smaller, with diameters of 2.5 and 2.3 microns, conduction velocities of 15 and 19 m/s, and terminal fields made up of a few small boutons at the borders of the ventral posterior lateral nucleus (VPL). 4. Of 319 neurons isolated, 14 out of 129 (10.8%) in VL, 14 out of 76 (18.4%) in the VPL or ventral posterior medial (VPM) nucleus, 27 out of 64 (42.2%) in the CL nucleus, and 5 out of 50 (10%) in the reticular nucleus (R) responded at latencies less than 50 ms to VLF stimuli. A train of three pulses was more effective in driving VLF-responding neurons in all these nuclei than a single pulse. VLF-responding cells were widely dispersed in VL, concentrated in a focus in CL, and distributed around the borders of VPL. Most of those in VL and a small number in CL could be antidromically activated by stimulation of motor cortex. 5. Latencies of presynaptic responses (STT fibers) to VLF stimulation were short and varied from 0.8 to 3.9 ms (mode 1.6 ms). Despite this, very few fast-responding neurons were found. These were six VPL neurons (2.5 to 4 ms), one VL neuron (3 ms), and four CL neurons (3-4 ms). The initial spike latencies of the majority of thalamic neurons responding to VLF stimulation appeared in two peaks, one between 6 and 8 ms and the other at 10-15 ms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753275 TI - Reorganization of somatosensory area 3b representations in adult owl monkeys after digital syndactyly. AB - 1. These experiments were designed to test the hypothesis that temporally correlated afferent input activity plays a lifelong role in the establishment and modification of receptive fields (RFs) and representational topographies in the primary somatosensory cortex of adult monkeys. They were based in part on the finding that adjacent digits of the hand are represented discontinuously in area 3b of the adult owl monkey. If cortical receptive fields and the details of cortical topographic representations are shaped by the weights of the temporal correlations among afferent inputs, then representational discontinuities between digits would be expected to arise because inputs from the skin surfaces of adjacent digits are largely independent in the critical time domain. 2. In the present experiments, the skin of adjacent digits 3 and 4 of the monkey hand was surgically connected to create an artificial syndactyly, or webbed-finger condition. Highly detailed microelectrode maps of the cortical representation of the syndactyl digits were obtained 3-7.5 mo later. This experimental manipulation greatly increased the amount of simultaneous or nearly simultaneous input from the normally separated, now fused, surfaces of adjacent fingers. 3. Cortical maps of the representations of finger surfaces were highly modified from the normal after a several-month-long period of digital fusion. Specifically, the normal discontinuity between the cortical representations of adjacent fingers was abolished. Within a wide cortical zone, RFs were defined that extended across the line of syndactyly onto the surgically joined skin of both fused digits. The representational topography of the fused digits was similar to any normal single digit and was characterized by a continuous progression of partially overlapping RFs. 4. Control observations revealed that these reorganizational changes cannot be accounted for by any changes in cutaneous innervation induced by the surgery. They must arise from representational changes in the central somatosensory system. 5. These findings reveal that cortical maps can be altered in detail in adult monkeys by modifying the distributed temporal structure of afferent inputs. They support the longstanding hypothesis that the temporal coincidence of inputs plays a role in the grouping of input subsets into specific cortical RFs and, consequently, in the shaping of selected effective cortical inputs and representational topographies throughout life. PMID- 1753276 TI - Saccade-related activity in the lateral intraparietal area. I. Temporal properties; comparison with area 7a. AB - 1. The cortex of the inferior parietal lobule (IPL) contains neurons whose activity is related to saccadic eye movements. The exact role of the IPL in relation to saccades remains, however, unclear. In this and the companion paper, we approach this problem by quantifying many of the spatial and temporal parameters of the saccade-related (S) activity. These parameters have hitherto been largely unstudied. 2. The activity of single neurons was recorded from Macaca mulatta monkeys while they were performing a delayed-saccade task. The analysis presented here is based on 161 neurons recorded from the lateral intraparietal area (LIP), a recently defined subdivision of the IPL; and 54 neurons recorded from the neighboring part of the IPL, area 7a. Overall, 409 IPL neurons were isolated in this study. 3. The typical activity of IPL neurons during the delayed-saccade task has three basic phases: light sensitive (LS), memory (M), and S. These basic phases are common to neurons of both areas LIP and 7a. In each phase (LS, M, and S), individual neurons may or may not be active. Most LIP neurons, however, are active in more than one phase. 4. To compare the activity levels of different neurons, the actual firing rate was weighted by each neuron's background level, yielding an "activity index" for each neuron, in each phase of the task. We calculated the activity index for the LS and M phases and for three phases related to the saccade: a presaccadic (Pre-S), a saccade coincident (S-Co), and a postsaccadic (Post-S) phase. For area LIP neurons the median values of the activity index were high for the LS, M, Pre-S, and S-Co activities, and slightly lower in the Post-S period. In area 7a the median values were low for the LS phase and, in particular, for the M and Pre-S phases, somewhat higher coincident with the saccade, and high post-saccadically. 5. In area LIP, in each phase, 49-63% of the neurons had excitatory activity, and 10 17% had inhibitory responses. 6. In contrast, in area 7a excitatory responses were most frequent in the Post-S phase (56%). Excitation was particularly infrequent during M (28%) and Pre-S (22%). The incidence of inhibitory responses varied too (4-18%). The time course of inhibition was roughly opposite that of excitation; the highest frequency of inhibitory responses occurred during the saccade.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753277 TI - Saccade-related activity in the lateral intraparietal area. II. Spatial properties. AB - 1. Single-neuron activity was recorded from the inferior parietal lobule (IPL) of Macaca mulatta monkeys while they were performing delayed saccades and related tasks. Temporal characteristics of this activity were presented in the companion paper. Here we focus on the spatial characteristics of the activity. The analysis was based on recordings from 145 neurons. All these neurons were from the lateral intraparietal area (LIP), a recently defined subdivision of the IPL. 2. Delayed saccades were made in eight directions. Direction-tuning curves were calculated for each neuron, during each of the following activity phases that were described in the companion paper: light sensitive (LS), delay-period memory (M), and saccade related (S); the latter further partitioned into presaccadic (Pre-S), saccade coincident (S-Co), and postsaccadic (Post-S). 3. Width and preferred direction were calculated for each direction-tuning curve. We studied the distributions of widths and preferred directions in LIP's neuronal population. In each case we included only neurons that showed clear excitatory activity in the phases in question. 4. Width was defined as the angle over which the response was higher than 50% of its maximal net value. Width distributions were similar for all phases studied. Widths varied widely from neuron to neuron, from very narrow (less than 45 degrees) to very wide (close to 360 degrees). Median widths were approximately 90 degrees in all phases. 5. Preferred-direction distributions were also similar for various phases. All directions were represented in each distribution, but contralateral directions were more frequent (e.g., 69% for S Co). 6. For each neuron the alignment of the preferred directions of its various phases was determined. Distributions of alignments were calculated (again, phases that were not clearly excitatory were disregarded). On the level of the neuronal population LS, M, and Pre-S were well aligned with each other. S-Co was also aligned with these phases, but less precisely. 7. A set of "narrowly tuned" neurons was selected by imposing a constraint of narrow (width, less than 90 degrees) LS and S-Co direction tuning. In this set of neurons, the LS and S-Co preferred directions were very well aligned (median, 12 degrees). The fraction of narrowly tuned neurons in the population was 40% (25/63). Thus, in a large subpopulation of area LIP, a fairly precise alignment exists between sensory and motor fields. 8. An additional set of 82 area LIP neurons were recorded while the monkey performed delayed saccades to 32 targets located on small, medium, and large imaginary circles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753278 TI - Recovery of function after lesions in the superior temporal sulcus in the monkey. AB - 1. Ibotenic acid lesions in the monkey's middle temporal area (MT) and the medial superior temporal area (MST) in the superior temporal sulcus (STS) have previously been shown to produce a deficit in initiation of smooth-pursuit eye movements to moving visual targets. The deficits, however, recovery within a few days. In the present experiments we investigated the factors that influence that recovery. 2. We tested two aspects of the monkey's ability to use motion information to acquire moving targets. We used eye-position error as a measure of the monkey's ability to make accurate initial saccades to the moving target. We measured eye speed within the first 100 ms after the saccade to evaluate the monkey's initial smooth pursuit. 3. We determined that pursuit recovery was not dependent specifically on the use of neurotoxic lesions. Although the rate of recovery was slightly altered by replacing the usual neurotoxin (ibotenic acid) with another neurotoxin [alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] or with an electrolytic lesion, pursuit recovery still occurred within a period of days to weeks. 4. There was a relationship between the size and location of the lesion and the recovery time. The time to recovery for eye position error and initial eye speed increased with the fraction of MT removed. Whether the rate of recovery and size of lesions within regions on the anterior bank were related was unresolved. 5. We found that a large AMPA lesion within the STS that removed all of MT and nearly all of MST drastically altered the rate of recovery. Recovery was incomplete more than 7 mo after the lesion. Even with this lesion, however, the monkey's ability to use motion information for pursuit was not completely eliminated. 6. The large lesion also included parts of areas V1, V2, V3, and V4, but analysis of the visual fields associated with this lesion indicated that these areas probably did not have a substantial effect on recovery. 7. We tested whether visual motion experience of the monkey after a lesion was necessary for recovery by limiting the monkey's experience either by using a mask or by using 4-Hz stroboscopic illumination. In one monkey the eye position error component of pursuit was prolonged to greater than 2 wk, but recovery of eye speed was not. Reduced motion experience had little effect on recovery in the other two monkeys. These results suggest that such visual motion experience is not necessary for the recovery of pursuit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753279 TI - Fast rhythms in phrenic motoneuron and nerve discharges. AB - 1. Fast rhythms in discharges of individual phrenic (PHR) motoneurons were studied by spectral and interval analyses; and they were compared, using coherence analysis, with similar rhythms in whole-PHR nerve discharge. The purpose of this study was to ascertain the origin of the two rhythms, manifested as distinct spectral peaks, in PHR motoneuron and nerve discharge: medium frequency oscillations (MFO, usual range 20-50 Hz); and high-frequency oscillations (HFO, usual range 50-100 Hz). 2. In paralyzed artificially ventilated cats, unit recordings were taken from 1) 26 isolated single PHR fibers (in 8 sodium pentobarbital-anesthetized cats) and 2) 27 identified PHR motoneuron somata in the spinal cord (in 5 decerebrate cats). Simultaneous whole-PHR activity was monophasically recorded from the contralateral PHR nerve for 1 and from both PHR nerves for 2. 3. The signals were subjected to time- and frequency domain analyses. The latter included a novel application of coherence analysis to the study of population synchrony. 4. The autospectra of all PHR units showed prominent MFO peaks in the frequency range of the nerve MFO spectral peaks, as well as harmonic peaks, indicating the presence of this type of fast rhythm in the units' discharges. Spectral analysis of the augmenting PHR activities in different segments of the inspiratory (I) phase showed that the frequency of unit MFO and of nerve MFO rose during the course of I. Further, cycle-triggered histogram and interval analysis indicated that the frequencies of unit MFO autospectral peaks were very close to the peak firing rates of the units during the portion of I analyzed. Thus unit MFO spectral peaks reflected the rhythmic and augmenting discharges of the motoneurons, and similar nerve MFO peaks reflected the superposition of individual motoneuron discharges. 5. The coherences of motoneurons' MFOs to nerve MFOs were low or zero, indicating that only partial and weak MFO correlations occurred within the PHR motoneuron population. 6. In those cats (n = 11) that had clear PHR nerve HFO spectral peaks, about one-half of the recorded PHR motoneurons had HFO, as indicated by HFO peaks in the unit autospectra and/or the unit-nerve coherences. 7. For motoneurons having HFO, the coherence between unit and nerve HFOs was substantial, particularly when the latter were strong, indicating HFO correlations among a number of PHR motoneurons. 8. In the light of theoretical considerations on the generation of aggregate rhythms from superposition of unitary rhythms, these observations indicate the following.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753280 TI - Synaptic potentials evoked by convergent somatosensory and corticocortical inputs in raccoon somatosensory cortex: substrates for plasticity. AB - 1. "Unmasking" of weak synaptic connections has been suggested as a mechanism for the early changes in cortical topographic maps that follow alterations of sensory activity. For such a mechanism to operate, convergent sensory inputs must already exist in the normal cortex. 2. We tested for topographic and cross-modality convergence in primary somatosensory cortex of raccoon. The representation of glabrous skin of forepaw digits was chosen because, even though it is dominated by inputs from the glabrous skin of a single digit, it nevertheless comes to respond to stimulation of other digits when, e.g., a digit is removed. 3. Intracellular recordings were made from 109 neurons in the representation of glabrous skin of digit 4. Neurons were tested for somatosensory inputs with electrical and natural stimulation of digits. 4. Excitatory postsynaptic potentials (EPSPs) were evoked in 100% of the neurons (109/109) by electrical stimulation of glabrous skin of digit 4, and in 79% (31 of 39) by vibrotactile stimulation. 5. Glabrous skin of digit 4 was not the sole source of somatosensory inputs. A minority of neurons generated EPSPs after electrical stimulation of hairy skin of digit 4 (10 of 98 neurons, 10%). Electrical stimulation of digits 3 or 5 evoked EPSPs in 22 of 103 neurons (21%). Natural stimulation (vibrotactile or hair bending) was also effective in most of these latter cases (digit 3, 6/7; digit 5, 9/10). 6. Intracortical microstimulation of the "heterogeneous zone" was used to test for corticocortical connections to neurons in the glabrous zone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753281 TI - Influence of map scale on primary afferent terminal field geometry in cat dorsal horn. AB - 1. Thirty-one physiologically identified primary afferent fibers were labeled intracellularly with horseradish peroxidase (HRP). 2. A computer analysis was used to determine whether the distribution of cutaneous mechanoreceptive afferent terminals varies as a function of location within the dorsal horn somatotopic map. 3. An analysis of the geometry of the projections of these afferents has shown that 1) terminal arbors have a greater mediolateral width within the region of the foot representation than lateral to it, 2) terminal arbors have larger length-to-width ratios outside the foot representation than within it, and 3) the orientation of terminal arbors near the boundary of the foot representation reflects the angle of the boundary. Previous attribution of mediolateral width variations to primary afferent type are probably in error, although there appear to be genuine variations of longitudinal extent as a function of primary afferent type. 4. Nonuniform terminal distributions represent the first of a three component process underlying assembly of the monosynaptic portions of cell receptive fields (RFs) and the somatotopic map. The other two components consist of the elaboration of cell dendritic trees and the establishment of selective connections. 5. The variation of primary afferent terminal distributions with map location is not an absolute requirement for development of the map; for example, the RFs of postsynaptic cells could be assembled with the use of a uniform terminal distribution for all afferents, everywhere in the map, as long as cell dendrites penetrate the appropriate portions of the presynaptic neuropil and receive connections only from afferent axons contributing to their RFs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753282 TI - Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements. AB - 1. Single-cell activity was recorded from three different motor areas in the cerebral cortex: the primary motor cortex (MI), supplementary motor area (SMA), and premotor cortex (PM). 2. Three monkeys (Macaca fuscata) were trained to perform a sequential motor task in two different conditions. In one condition (visually triggered task, VT), they reached to and touched three pads placed in a front panel by following lights illuminated individually from behind the pads. In the other condition (internally guided task, IT), they had to remember a predetermined sequence and press the three pads without visual guidance. In a transitional phase between the two conditions, the animals learned to memorize the correct sequence. Auditory instruction signals (tones of different frequencies) told the animal which mode it was in. After the instruction signals, the animals waited for a visual signal that triggered the first movement. 3. Neuronal activity was analyzed during three defined periods: delay period, premovement period, and movement period. Statistical comparisons were made to detect differences between the two behavioral modes with respect to the activity in each period. 4. Most, if not all, of MI neurons exhibited similar activity during the delay, premovement, and movement periods, regardless of whether the sequential motor task was visually guided or internally determined. 5. More than one-half of the SMA neurons were preferentially or exclusively active in relation to IT during both the premovement (55%) and movement (65%) periods. In contrast, PM neurons were more active (55% and 64% during the premovement and movement periods) in VT. 6. During the instructed-delay period, a majority of SMA neurons exhibited preferential or exclusive relation to IT whereas the activity in PM neurons was observed equally in different modes. 7. Two types of neurons exhibiting properties of special interest were observed. Sequence-specific neurons (active in a particular sequence only) were more common in SMA, whereas transition-specific neurons (active only at the transitional phase) were more common in PM. 8. Although a strict functional dichotomy is not acceptable, these observations support a hypothesis that the SMA is more related to IT, whereas PM is more involved in VT. 9. Some indications pointing to a functional subdivision of PM are obtained. PMID- 1753283 TI - Delayed activation of nociceptors: correlation with delayed pain sensations induced by sustained stimuli. AB - 1. In this study we used psychophysical experiments in humans and behavioral and electrophysiological studies in rats to evaluate nociceptive and C-fiber mechanoheat nociceptor (C-MH) responses to sustained mechanical stimuli that are initially nonpainful or nonnoxious. 2. In normal rat skin, sustained subthreshold mechanical stimuli activate C-MHs (n = 36) with a delayed onset that parallels the delayed pain sensation recorded in human psychophysical tests. 3. The subthreshold stimuli did not induce a decrease in mechanical threshold (n = 11), and the effect of the subthreshold stimulus on latency to firing of C-MHs (n = 6) persists for a very short time after the stimulus is removed (less than 10 s). 4. Intradermal injection of prostaglandin E2 (PGE2; 100 ng), which induced a significant decrease in the mechanical threshold of C-MHs (n = 7), had no effect on the latency of the delayed activation of C-MHs. Also, indomethacin, which inhibits the synthesis of prostaglandins, had no effect on the latency of the delayed paw-withdrawal response in the behavioral test. 5. Intradermal injection of the calcium ionophore A23187 significantly reduced the latency of the delayed activation of C-MHs (n = 6) the calcium chelator Quin 2 (n = 6) significantly increased the latency. A23187 and Quin 2 had similar effects on the latencies to paw withdrawal in behavioral tests. The sensitization of C-MHs (n = 9) by PGE2 was not, however, affected by Quin 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753284 TI - Somatotopic mapping of the primary motor cortex in humans: activation studies with cerebral blood flow and positron emission tomography. AB - 1. The somatotopic representation of the human primary motor cortex was examined noninvasively with estimates of cerebral blood flow (CBF) obtained with positron emission tomography. Twelve normal subjects performed a motor tracking task with the arm, first finger, tongue, and great toe commensurate with the bolus injection of radioactive H215O. Images of the relative percent increase of blood flow, compared with control studies, demonstrated reproducible foci of CBF increases in the motor cortex in every subject. Each motor task could be localized to a predictable site on a coronal section containing the precentral gyrus. 2. In reproducibility experiments of repeated measures, it was determined that two foci of activation in the primary motor cortex could be discriminated with a 95% confidence if they were separated by 5.4 mm. 3. In five subjects with matched magnetic resonance imaging studies, the sites of activation were variable with respect to surface anatomy and could be found at the depth of sulci or the surface of gyri. The findings were similar to previously reported electrophysiological studies using direct cortical stimulation. 4. The method may be applied to the in vivo functional mapping of the primary motor cortex in patients with cerebral disorders. PMID- 1753285 TI - Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs. AB - 1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753286 TI - Effect of neonatal denervation of hindlimb digits on the somatotopic organization of lumbar spinocervical tract neurons in the cat. AB - 1. The effect of transection and ligation of the digital nerves of either one (toe 3) or two (toe 3 and toe 4) hindpaw digits, in the first postnatal week, on the tactile receptive fields (RFs) of spinocervical tract (SCT) neurons was studied in adult, alpha-chloralose-anesthetized cats. Immediately before recording, the digital nerves of the corresponding digit(s) of the opposite, intact hindpaw were transected, and the neonatally lesioned digital nerves were recut proximal to the transection neuroma. 2. In the medial part of the dorsal horn at the L6-L7 level, the digits of the hindlimb are represented in the RFs of SCT cells in a precise axial sequence from the most medial digit (toe 2) rostrally to the most lateral digit (toe 5) caudally. Acute denervation of one or two digits in the adult produced an area in the ipsilateral dorsal horn in which SCT cells lacked any RFs. When acute denervation was restricted to a single digit, the unresponsive region of dorsal horn was approximately 3 mm in length, and when two digits were denervated the unresponsive zone was approximately 6 mm long. Because the representation of the toes of the left hindpaw is a mirror image of that of the right, the rostrocaudal extent and position of the region of unresponsive SCT cells was used to assess the location of the borders of the chronically deprived region on the opposite side of the cord. 3. In all cats examined after neonatal denervation of toe 3, most (89%) of the SCT cells sampled within the chronically deprived toe 3 representation had RFs. These RFs were either on toe 2 (44%) or toe 4 (18%), and a large proportion of cells (38%) had multiple RFs with components on both toe 2 and toe 4. In most cases the cells fired briskly to displacement of hairs or light touch of the skin within these RFs. SCT cells with a RF on toe 2 and/or toe 4 were found throughout the whole 3 mm length of the chronically deprived toe 3 region, but cells with a RF on toe 2 were more commonly found than cells with a RF on toe 4 at axial distances greater than or equal to 1.5 mm from the boundary of the normal representations of the respective digit. 4. After chronic, neonatal denervation of both toe 3 and toe 4, 59% of SCT cells sampled overall had RFs, but there was a large degree of interanimal variation in the proportion of unresponsive neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753287 TI - Lateral geniculate neurons in behaving primates. I. Responses to two-dimensional stimuli. AB - 1. Using behaving monkeys, we studied the visual responses of single neurons in the parvocellular layers of the lateral geniculate nucleus (LGN) to a set of two dimensional black and white patterns. We found that monkeys could be trained to make sufficiently reliable and stable fixations to enable us to plot and characterize the receptive fields of individual neurons. A qualitative examination of rasters and a statistical analysis of the data revealed that the responses of neurons were related to the stimuli. 2. The data from 5 of the 13 "X like" neurons in our sample indicated the presence of antagonistic center and surround mechanisms and linear summation of luminance within center and surround mechanisms. We attribute the lack of evidence for surround antagonism in the eight neurons that failed to exhibit center-surround antagonism either to a mismatch between the size of the pixels in the stimuli and the size of the receptive field or to the lack of a surround mechanism (i.e., the type II neurons of Wiesel and Hubel). 3. The data from five other neurons confirm and extend previous reports indicating that the surround regions of X-like neurons can have nonlinearities. The responses of these neurons were not modulated when a contrast reversing, bipartite stimulus was centered on the receptive field, which suggests a linear summation within the center and surround mechanisms. However, it was frequently the case for these neurons that stimuli of identical pattern but opposite contrast elicited responses of similar polarity, which indicates nonlinear behavior. 4. We found a wide variety of temporal patterns in the responses of individual LGN neurons, which included differences in the magnitude, width, and number of peaks of the initial on-transient and in the magnitude of the later sustained component. These different temporal patterns were repeatable and clearly different for different visual patterns. These results suggest that visual information may be carried in the shape as well as in the amplitude of the response waveform. PMID- 1753288 TI - Lateral geniculate neurons in behaving primates. II. Encoding of visual information in the temporal shape of the response. AB - 1. We used the Karhunen-Loeve (K-L) transform to quantify the temporal distribution of spikes in the responses of lateral geniculate (LGN) neurons. The basis functions of the K-L transform are a set of waveforms called principal components, which are extracted from the data set. The coefficients of the principal components are uncorrelated with each other and can be used to quantify individual responses. The shapes of each of the first three principal components were very similar across neurons. 2. The coefficient of the first principal component was highly correlated with the spike count, but the other coefficients were not. Thus the coefficient of the first principal component reflects the strength of the response, whereas the coefficients of the other principal components reflect aspects of the temporal distribution of spikes in the response that are uncorrelated with the strength of the response. Statistical analysis revealed that the coefficients of up to 10 principal components were driven by the stimuli. Therefore stimuli govern the temporal distribution as well as the number of spikes in the response. 3. Through the application of information theory, we were able to compare the amount of stimulus-related information carried by LGN neurons when two codes were assumed: first, a univariate code based on response strength alone; and second, a multivariate temporal code based on the coefficients of the first three principal components. We found that LGN neurons were able to transmit an average of 1.5 times as much information using the three-component temporal code as they could using the strength code. 4. The stimulus set we used allowed us to calculate the amount of information each neuron could transmit about stimulus luminance, pattern, and contrast. All neurons transmitted the greatest amount of information about stimulus luminance, but they also transmitted significant amounts of information about stimulus pattern. This pattern information was not a reflection of the luminance or contrast of the pixel centered on the receptive field. 5. In addition to measuring the average amount of information each neuron transmitted about all stimuli, we also measured the amount of information each neuron transmitted about the individual stimuli with both the univariate spike count code and the multivariate temporal code. We then compared the amount of information transmitted per stimulus with the magnitudes of the responses to the individual stimuli. We found that the magnitudes of both the univariate and the multivariate responses to individual stimuli were poorly correlated with the information transmitted about the individual stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753289 TI - Lateral geniculate neurons in behaving primates. III. Response predictions of a channel model with multiple spatial-to-temporal filters. AB - 1. For the experiments reported in these papers, we recorded the responses of lateral geniculate (LGN) neurons to a large set of two-dimensional, black and white patterns based on Walsh functions and to a set of test stimuli. In the first two papers we reported that these neurons encode stimulus-related information in both the strength and the shape of the response waveforms and that there are more than two independent components in the response. These results cannot be explained by existing models. This paper provides a model of LGN neurons that not only accounts for the foregoing observations, but also yields predictions confirmed by direct tests. 2. The model represents a neuron as a set of three parallel channels. The input to each channel is an array of pixel luminances. Each channel consists of an input nonlinearity cascaded into a linear spatial-to-temporal filter. The output of each channel is a basic waveform, a principal component. The response of the neuron is the sum of the outputs of the three channels. 3. The model accounted for much of the variance in the coefficients of the first three principal components of the neuronal responses to the set of Walsh stimuli. Using parameters derived from the responses of neurons to the Walsh stimuli only, the model also predicted the responses to "center surround" annuli of different contrasts and mean luminances, as well as to superpositions of pairs of Walsh patterns. The model made statistically significant predictions of the coefficients of two of the principal components of these responses. 4. After the parameters of the model had been fit to reproduce the responses of neurons to the Walsh stimuli, we found that the input nonlinearity of the model was compressed at both the high and low luminance levels. This compression produced response saturation that closely resembled the response saturation of neurons reported in the first paper in this series. Although not absolutely smooth, the spatial filter for the first channel had a dominant excitatory or inhibitory center and an antagonistic surround. Thus this spatial filter accounted for both the center and the surround structures of previous models of LGN receptive fields. There was greater variety in the structures of the spatial filters for the second and third channels, but none had a center-surround organization. Many of the spatial filters for these higher channels contained oriented ridges or valleys. Other spatial filters were dominated by a bipolar pair of pixels. 5. The model of LGN neurons that we present in this paper represents an extension over previous models in four ways. First, the model is capable of explaining the responses of neurons to a wider range of luminances than previous models. Second, the model is capable of explaining the shapes of the response waveforms as well as their magnitudes. Third, the concept of a single receptive field is extended to a series of spatial to-temporal filters. Fourth, the model suggests that LGN neurons provide a description of both the brightness and the form of a stimulus in their response waveforms. PMID- 1753290 TI - Ocular responses to translation and their dependence on viewing distance. I. Motion of the observer. AB - 1. The horizontal eye movements induced by acceleration along the interaural axis were recorded from five monkeys (Macaca mulatta) by the use of the electromagnetic search-coil technique. Animals sat on a sled that was moved briefly in darkness along a linear track (bell-shaped acceleration profile: peak, 400 mm/s2; duration, 200 ms). Immediately before acceleration, animals fixated one of five target lights located at distances ranging from 16 to 150 cm. During fixation, the horizontal positions of both eyes were used to check vergence, while accommodation was monitored with an infrared optometer. 2. Sled motion induced eye movements that were generally smooth and compensatory, e.g., rightward sled motion elicited leftward eye movement. We attribute these responses to a translational vestibuloocular reflex (TVOR) that senses the sled motion through the otolith organs. However, in three animals, these responses were preceded by weak anticompensatory movements (duration, less than 40 ms; amplitude, less than 10% of the maximum compensatory response). 3. Geometry indicates that, during brief sled motion, the eye movements required to keep gaze aligned on a particular location ("full" compensation) are inversely proportional to the viewing distance. Response measures based on the computed eye velocity profiles, such as the velocity achieved at specific times ("time slices") or the peak values of the estimated covariance functions, all indicated that compensatory responses were a linear function of the inverse of the prior viewing distance. Cross-correlation analyses indicated that the effect of the prior viewing distance was to scale responses, although detailed spectral analyses revealed that high-frequency components (greater than 10 Hz) tended to scale less vigorously than lower ones. 4. The adequacy of the compensatory eye movements was assessed by calculating the gain (response recorded/response required for full compensation). Regardless of the response measure used, gains varied considerably from one animal to another and, in some particular animals, from one direction to another but showed a general tendency to increase with viewing distance. For example, on the basis of the peak eye velocity achieved within 250 ms of the onset of sled motion, mean gain at 16 cm was 0.74 (range, 0.48-1.01), whereas at 150 cm it was 1.25 (range, 0.67-1.73). 5. Using wedge prisms to dissociate vergence and accommodation indicated that ocular responses to sled motion were sensitive to selective increases in either vergence (base-out prism with the most distant target) or accommodation (base-in prism with the nearest target). However, the magnitude of the effects showed considerable variability from one animal to another and, in some particular animals, from one direction to another.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753291 TI - Ocular responses to translation and their dependence on viewing distance. II. Motion of the scene. AB - 1. The ocular following responses induced by brief (100-ms) movements of the visual scene were examined for their dependence on viewing distance in 5 monkeys (Macaca mulatta). The horizontal positions of both eyes and the vertical position of one eye were recorded using the electromagnetic search-coil technique. Accommodation was monitored in selected experiments by use of an infrared optometer. Test patterns (random dots) were back-projected onto a translucent tangent screen facing the animal. Six viewing distances were used (range, 20-150 cm), the size and speed of the image on the screen being adjusted for each so as to preserve a constant retinal image. 2. Response measures based on the amplitude of the first peak in the eye acceleration profile or the eye velocity achieved at specific times all indicated that ocular following responses were inversely related to viewing distance, the relationship being linear for the earliest measures. On average, the sensitivity to viewing distance was comparable with that reported for the translational vestibuloocular reflex (TVOR) in the preceding paper: as viewing distance increased from 20 cm, ocular following decremented at a mean rate (+/- SD) of 17 +/- 3% per m-1, while the TVOR decremented at a mean rate (+/- SD) of 18 +/- 1% per m-1. 3. Ocular following responses showed the postsaccadic enhancement described by Kawano and Miles regardless of viewing distance. To a first approximation, the effects of postsaccadic enhancement and viewing distance summed linearly. 4. The dependence of ocular following on speed showed the progressive saturation previously described by Miles et al. at all viewing distances, the peak eye velocity achieved being inversely related to the viewing distance, indicating that the saturation must originate upstream of the dependence on viewing distance. Under normal viewing conditions, this speed saturation will tend to offset the dependence on viewing distance because the retinal slip speeds experienced by the moving observer will tend to vary inversely with viewing distance, resulting in greater saturation with nearer viewing. 5. Wedge prisms were used to dissociate vergence and accommodation and indicated that ocular following responses were sensitive to selective increases in either vergence (base-out prism with the screen at 100 cm) or accommodation (base-in prism with the screen at 20 cm). However, as with the TVOR, the magnitude of the effects showed considerable variability from one animal to another and, in some particular animals, from one direction to another.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753292 TI - Activity of neurons in cerebellar-receiving and pallidal-receiving areas of the thalamus of the behaving monkey. AB - 1. Thalamic neurons that receive synaptic input from the globus pallidus or the cerebellar nuclei were identified in awake monkeys trained to perform an arm reaching task. The location of electrophysiologically identified cerebellar receiving (CR) and pallidal-receiving (PR) neurons was used to identify a total of 264 thalamic neurons in cerebellar (CB) or pallidal (GP) regions of the thalamus. 2. Stimulation in the brachium conjunctivum or white matter adjacent to the cerebellar nuclei excited 85 neurons in the thalamus at short latencies. These CR neurons were located in the oral portion of the ventral posterolateral nucleus (VPLo), in caudal portions of the ventral lateral nucleus (VLc), and in area X. 3. Stimulation in the internal globus pallidus (GPi) inhibited 10 thalamic neurons at short latency. These PR neurons were located in rostral portions of VLc, in the oral part of the ventral lateral nucleus (VLo), and in the parvicellular part of the ventral anterior nucleus (VApc). 4. There was no clear single somatotopic organization of neurons in CB and GP regions of the thalamus, as defined by "free-form" responses to passive manipulation and observation of eye movements. There was, in fact, a tendency for two representations, each, of the head/eye/mouth cells and cells with modifications of activity in response to manipulation of the arm. 5. During the hold period before illumination of a visual target, the mean firing rates and variability of discharge of arm-related CR and PR neurons did not differ significantly. This was also true for the total sample of arm-related neurons in the CB versus GP regions. 6. The activity of many neurons in both the CB and GP regions began to change before the reaching movement and, for some, before the earliest recorded changes in electromyographic (EMG) activity. The initial change was an increase in discharge for greater than 75% of the cells studied in both the CB and GP regions. 7. During the reaching task, there also was no significant difference in the time of the initial change in discharge of neurons in the CB versus GP regions of the thalamus. 8. These data are consistent with the hypothesis that the initial task-related change in discharge of PR thalamic neurons is dominated by input from the cerebral cortex and that pallidal input modulates later phases of their movement-related changes in activity. PMID- 1753293 TI - Intracellular analysis of excitatory-inhibitory synaptic interactions in crayfish stretch receptors. AB - 1. To determine the membrane mechanisms underlying the interactions between inhibitory postsynaptic potentials (IPSPs) and excitatory inputs, we investigated, at the membrane potential level, the combined influences of low frequency (0.05-0.50 Hz) imposed sinusoidal transmembrane currents (termed sine currents), representing the excitatory drive, and trains of regular (3-30/s) IPSPs. The two simplest possible neuron systems exemplified by the slowly and rapidly adapting stretch receptors of crayfish (RM1 and RM2, respectively) were used. 2. At constant elongation the RM1 and RM2 behaved as a pacemaker and a neuron without self-sustained oscillations, respectively, but in dynamic conditions uninhibited controls and IPSP sine current interactions were essentially identical in both RMs. Controls showed the usual smooth variation of the RM firing rate in response to the gradually varying excitatory input. IPSP effects were characterized by the expected overall reduction of the postsynaptic firing rate. More important, special effects were also present, such as the simple fixed alternations of IPSP and postsynaptic spikes (e.g., 1 IPSP, 1 postsynaptic or 1:1; 1 IPSP, 2 postsynaptic or 1:2; 2 IPSPs, 1 postsynaptic spike or 2:1), where interspike intervals were more constant than uninhibited controls and where the sensitivity to the excitatory input was reduced to small values, and the sudden firing rate discontinuities consisting of instantaneous discharge accelerations or decelerations (termed "jumps") between successive alteration ratios, where sensitivity increased to large values. Therefore with inhibition the RM firing rate varied discontinuously in response to the gradually changing input, and the discharge rate could take one of several discrete values by switching between different alteration ratios. 3. At the alternations the times elapsed between an IPSP and the closest spike before (phase, phi) or after it (cophase, theta) increased and decreased, respectively, with increasing excitation. The major membrane potential modification that accompanied the interactions at the alternations was the gradual increase of the post-IPSP slope as a function of excitatory drive, which reduced the time to reach the firing level or theta. 4. Inhibition introduced subtle and complex nonlinear modifications in the coding of convergent excitatory input. The most notable nonlinearity was the discontinuous variations of the firing rate as a function of the gradually changing excitatory input. Effects were due to voltage interactions occurring at the extrasynaptic membrane, with a decisive involvement of the spike generator and insignificant participation of the shunting action of IPSPs. The results provide yet another example of the predominant influence of intrinsic membrane properties in determining the effects of synaptic-evoked activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753294 TI - Effects of low-frequency stimulation on the tension-frequency relations of fast twitch motor units in the cat. AB - 1. Tension-frequency relations were measured in single fast-twitch motor units of the cat flexor digitorum longus (FDL) muscle before and after stimulating each unit with a series of 10-s trains at 20 Hz. The 20-Hz conditioning stimulation produced a combination of potentiating and fatiguing effects, similar to those previously reported to follow higher frequency stimulation of single motor units of the cat and maximal voluntary contractions in man. 2. The conditioning stimulation left three types of after effects: 1) short-term potentiation, 2) a somewhat longer lasting depression of maximal tension, and 3) a delayed depression of low-frequency responses (low-frequency fatigue). 3. The immediate potentiating effect of the conditioning stimulation was most prominent in fatigue resistant (FR) motor units, whereas depression of maximal tension and low frequency fatigue were most prominent in fatigue-intermediate (FI) and highly fatigable (FF) motor units. 4. On the basis of our results and those of other investigators, we propose that potentiation, depression of maximal tension, and low-frequency fatigue are independent phenomena, acting at distinct points in the excitation-contraction coupling process. 5. Our results suggest that both potentiation and low-frequency fatigue can result from rather modest amounts of preceding activity. Thus large changes in muscle force production are not unique to maximal contractions but are likely to follow sustained, submaximal contractions as well. PMID- 1753295 TI - Functional organization within the medullary reticular formation of the intact unanesthetized cat. III. Microstimulation during locomotion. AB - 1. This article presents the results from stimulation in 21 loci within the medullary reticular formation (MRF; between 0.5 and 2.5 mm from the midline) and in 5 loci in the medial longitudinal fasciculus (MLF) of four intact, unanesthetized cats during locomotion. Stimulus trains (11 pulses, 0.2-ms duration, 330 Hz, stimulus strength 35 microA) were applied at those loci in each track at which the most widespread effects in each of the four limbs were obtained with the cat at rest. Electromyograms were recorded from flexor and extensor muscles of each limb. 2. As previously reported, stimulation with the cat at rest generally evoked brief, short-latency, twitch responses in both flexor and extensor muscles of more than one limb. In contrast, stimulation during locomotion evoked a more complex pattern of activity in which responses were normally evoked in one or other of the muscle pairs and incorporated into the locomotor pattern. 3. In the majority of sites, the stimulation evoked excitatory responses in the flexor muscles of each of the four limbs during that period of the step cycle in which each respective muscle was naturally active; stimulation in the stance phase of locomotion, although less effective, was also capable of producing responses in these muscles. All three ipsilateral extensor muscles studied [long and lateral heads of triceps and vastus lateralis (Tri, TriL, and VL, respectively)] were normally inhibited during their phase of muscle activity, although excitatory responses were occasionally seen. Responses in the contralateral (co) Tri were invariably excitatory and were largest during the period of muscle activity, whereas responses during the period of activity of the coVL were mixed, with both excitatory and inhibitory responses being seen from any one locus. 4. Excitatory responses were normally largest when stimulation was applied during the time that the muscle was active during the locomotor cycle. Responses evoked at times when the muscle was inactive were sometimes larger than those evoked with the animal at rest; such responses were most commonly seen in the hindlimb flexors and in the coVL. 5. In both flexors and extensors of each of the four limbs, the latency of the responses was greatest when the cat was at rest and least for stimuli given during the period of activity of the respective muscle. Average latencies during the period of muscle activity ranged from a minimum of 9.0 +/- 2.6 (SD) ms for inhibitory responses in the ipsilateral Tri and TriL to a maximum of 17.1 +/- 3.0 ms for the responses evoked in the ipsilateral semitendinosus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753296 TI - Transient reversal of the stretch reflex in human arm muscles. AB - 1. Load perturbation responses can violate the law of reciprocal innervation between antagonist muscles under particular conditions. Thus flexor and extensor muscles of wrist and elbow joints are reflexly coactivated by the impact of a ball on the hand during a catching task. The aim of this study was to determine whether reflex coactivation can be preset within the central nervous system (CNS) or whether it is entirely due to the peripheral stimulus. To this end, we studied the behavior of stretch reflex responses of arm muscles evoked by torque motor perturbations applied before and during the catching task. 2. Subjects were instructed to catch a ball dropped from 1.6 m. A torque motor delivered perturbations to the elbow joint, resulting in angular motion at both elbow and wrist joints because of their dynamic mechanical coupling. Two series of experiments were performed that differed in the perturbation waveform. In the first series, a single torque pulse could be randomly applied at different times during the task. The corresponding responses were recovered by subtracting the average of the unperturbed trials from the averages of perturbed trials. In the second series of experiments, a train of pseudorandom pulses was applied continuously during each trial. The time-varying impulse responses were computed at 20-ms intervals by cross-correlation methods. 3. The pattern of the short latency electromyographic responses evoked by either single pulses or pseudorandom perturbations obeyed the law of reciprocal innervation of antagonist muscles under basal conditions. However, the pattern of the responses evoked by the same perturbations around the time of ball impact on the hand consisted of a substantial coactivation of both stretched and shortening muscles. Reflex coactivation resulted from response patterns that differed at different joints. At the elbow, reflex coactivation resulted from a transient reversal of the direction of the short-latency responses of flexor muscles, with little changes of the responses of extensor muscles. At the wrist, instead, reflex coactivation resulted from simultaneous changes in the response waveform of both flexor and extensor muscles. 4. The peripheral conditions associated with the applied perturbations were constant before the time of ball impact. Thus, because the changes of the stretch reflex responses began before that time, they must have been generated within the CNS. It is here hypothesized that the reversal of the reflex responses is centrally gated by switching from the pathways of reciprocal inhibition to those of coactivation of antagonist alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753297 TI - Parabrachial gustatory neural activity during licking by rats. AB - 1. A total of 51 single neurons was recorded from the pontine parabrachial nuclei of three rats being given sapid stimuli either via intraoral infusions or during spontaneous licking behavior. In 46 neurons, sapid stimuli elicited significant taste responses; of these, 28 responded best to NaCl, 15 to sucrose, 2 to citric acid, and 1 to quinine HCl. The remaining five neurons responded significantly only to water. The mean spontaneous rate of taste neurons during the intraoral infusion and licking sessions was 11.1 +/- 1.1 and 10.8 +/- 1.2 (SE) spikes/s, respectively. 2. Of the 39 neurons tested during both licking and intraoral infusions, four responded significantly only to water via either route. The remaining 35 neurons responded significantly to at least some sapid stimuli. The best-stimulus categories remained the same regardless of the route of fluid delivery (24 NaCl best, 10 sucrose best, 1 citric acid best). When the rats were licking the stimuli, nine taste neurons responded significantly to only one sapid chemical [6 Na specific (Ns) and 3 sucrose specific (Ss)] but were more broadly tuned during intraoral infusions. Conversely, three taste neurons that responded specifically during intraoral infusions (3 Na specific) were not as specific when the animal licked the same fluids. 3. Thirty-five taste neurons were tested via both stimulus routes. These data were compared in three ways. First, for each neuron, the responses elicited during licking and intraoral infusions were compared for each of the four standard sapid stimuli. The Pearson correlation coefficients for the 35 taste neurons ranged from 0.9997 to 0.6785, with a mean at 0.953 +/- 0.012 (SE). The second comparison was between stimulus routes across chemicals. With the use of raw responses, the correlation coefficients for NaCl, sucrose, citric acid, and QHCl ranged from 0.925 to 0.778 (t test, P less than 0.0001). With the activity elicited by water subtracted (corrected responses), the correlation coefficients for NaCl, sucrose, citric acid, and QHCl were 0.900, 0.795, 0.369, and 0.211, respectively. The coefficient for QHCl was not significant (t test, P greater than 0.05). Finally, the mean responses to NaCl, sucrose, and citric acid delivered by both routes were compared and found not to differ (paired t test, P greater than 0.05). 4. In separate hierarchical cluster analyses for the licking and infusion data, the largest cluster in each contained all of the Na-best neurons and the next largest, all of the sucrose-best cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1753298 TI - Residency training in occupational and environmental medicine. PMID- 1753299 TI - Tobacco use: selection, stress, or culture? AB - The effects of selection, job stress, and culture models on the association between occupation and smoking were empirically estimated on a random sample of 2,362 employed adults in Orange County, California using data collected through the Orange County Health Survey. The largest percent of smokers were blue-collar workers (32.4%). The logistic regression analysis results indicated that age, sex, education, ethnicity, job stress, and the industry in which employees work had significant impact on the risk of smoking. The findings imply that all three models contribute to smoking behavior. Smoking cessation and prevention programs may include elements that address both stress and environment in intervention design. Stress models imply that such program should focus on change in individual coping mechanisms; social environment models imply that change in group norms and attitudes is necessary. PMID- 1753300 TI - Business analysis in occupational health and safety consultations. AB - We present a method for incorporating business analysis into comprehensive health and safety consultations using as an example a plant with an elevated incidence of cumulative trauma disorders. Business information, including product and management history, short- and long-term corporate goals, functional analysis, profit history, organizational structure with respect to health and safety, and personnel and labor-management relationships are evaluated simultaneously with traditional ergonomic factors. The additional business data allow consultants to identify the full scope of etiologies and make practical, credible recommendations that are more likely to be adopted by management and labor. We propose that techniques of "business analysis" be routinely incorporated into occupational health and safety consultations. However, because collection and interpretation of these data require business skills outside the occupational safety and health expert's usual repertoire, the consulting team must include participants with business expertise. We have found that occupational health medical personnel with an understanding of business analysis concepts can be very effective advocates for changes in health and safety practices. We strongly recommend incorporating methods of business analysis into the occupational health and safety curriculum. PMID- 1753301 TI - Use of focus groups to study absenteeism due to illness. AB - Reasons for sick leaves are often complex and influenced by nonmedical factors. We have used focus groups, a qualitative research method, to study the relationship between working conditions and absenteeism due to illness in both an industrial company and an insurance company. We organized 10 focus groups within each company, with participants randomly selected from departments having similar work tasks within each company. According to the groups, the most important working conditions that influenced absenteeism were (a) feeling of well-being at work (mainly defined as security in social relations), (b) the organization of the work, and (c) the department leader. Factors considered to be less important included: number of employees, male/female ratios, group norms for absenteeism, age distribution, work-related illness, substance abuse, and work loads. There was substantial agreement between the groups, indicating that our findings may be relevant to other companies. PMID- 1753302 TI - Relative effects of flow-resistive and pressure-biased respiratory loading. AB - The effects of pressure-biased breathing (PBB), which simulates positive pressure respirator use, were studied in 15 volunteer subjects during laboratory exercise. PBB was compared with inspiratory resistance: dead space (ID) load and a no-load (N) situation. PBB had adverse subjective effects comparable with those of ID. Physiologically, PBB led to a small decrease in inspiratory time and an increase in expiratory time as well as an increase in the intensity of ventilatory effort as measured by the mean inspiratory flow rate. It is postulated, based on these findings, that PBB has significant effects on the resting lung volume, leading to both physiologic and subjective consequences. PMID- 1753303 TI - The identification of occupational lung disease from hospital discharge data. AB - The Bureau of Labor Statistics-State Health Department Select Committee on Occupational Illnesses and Injuries conducted a study of hospital discharge records to determine their usefulness for identifying cases of occupational disease. Four states searched the diagnosis fields on computerized hospital discharge records for selected occupational lung diseases; pneumoconiosis, extrinsic allergic alveolitis, and respiratory conditions due to chemical fumes and vapors. The hospital discharge data identified more cases of pneumoconiosis than did the BLS data systems. Numerous cases of extrinsic allergic alveolitis and respiratory conditions due to chemical fumes and vapors were also identified. Patterns evidenced in the data were generally consistent with current knowledge of the diseases. The inclusion of industry and occupation on the hospital discharge record, further study of the quality of diagnosis coding, and the use of these data by additional states will enhance the usefulness of these data for occupational disease surveillance. PMID- 1753304 TI - The noise hazard in a large health care facility. AB - A noise-level survey, dosimetry, and audiometric testing were conducted in a large health care facility to determine the areas with hazardous noise levels, the number of employees at risk, and the prevalence of noise-induced hearing loss (NIHL) among the exposed. Nine high-risk areas were identified, with readings of up to 110 dBA recorded. In the work force of approximately 6,000 employees, 321 were identified as exposed to potentially hazardous noise levels. Abnormal hearing patterns were observed in 59 (19%) of the 308 workers screened, with 36 cases of NIHL documented. The findings showed that noise is a serious hazard in many areas, that some cases of NIHL have developed from occupational exposure in this hospital, and that a control program is essential. PMID- 1753305 TI - Who's counting anyway? The problem with occupational safety and health statistics. PMID- 1753306 TI - Morbidity patterns among employees at a petroleum refinery. AB - This study examined the morbidity experience of a prospective cohort of 2132 male employees who worked at a petroleum refinery from 1981 through 1988. The morbidity data included all illness-absence episodes in excess of 5 days during the study period. Standardized morbidity ratios (SMRs) of disease prevalence were calculated using data from all manufacturing employees of the Shell Oil Company as an internal comparison group. As such, there is no potential bias associated with the "healthy worker effect" in this type of study design. Morbidity for all causes combined was virtually the same as that for the comparison group with 2,311 observed and 2,318 expected disease prevalence events. However, there were statistically increased prevalence of musculoskeletal system disorders (SMR = 136) and injuries (SMR = 125) among staff employees and skin and subcutaneous tissue disorders (SMR = 138) among production employees. A review of the original morbidity reports for these skin conditions revealed that none were due to exposure to chemical products or solvents. The SMR for neoplasms of the lymphatic and hematopoietic tissue among production employees was slightly elevated but was based on only three cases (2.4 expected). Of the three cases, none was due to leukemia. PMID- 1753307 TI - Use of the Mantel-Haenszel chi 2 overestimates precision in studies with sparse data. AB - Probability values or "test-based" confidence limits computed on the basis of the Mantel-Haenszel chi 2 statistic may be invalid if minimum cell-size requirements are not met. In 30 studies of occupational proportionate mortality published from 1985 through 1987, the Mantel-Haenszel chi 2 was used in potential violation of cell-size requirements in 21 studies. Sixteen (76%) studies included at least one value that, when compared with testing with the Poisson distribution, was erroneously reported as statistically significant at the 0.05 level. We conclude that by using the Mantel-Haenszel chi 2 with sparse data, some epidemiologists overestimate precision. PMID- 1753308 TI - How dangerous is work in Canada? Estimates of job-related fatalities in 482 occupations. AB - Data have been gathered from Labour Canada and the Quebec Workers' Compensation Board to examine estimates of mortality in 482 Canadian occupations. These data contain information on job-related fatalities within four-digit occupations for 1980, 1981, 1985, and 1986. Compared with comparable data from the United States, the estimates indicate that the incidence of job-related fatalities is significantly higher in Canada. PMID- 1753309 TI - Methodological issues for the assessment of clusters of adverse pregnancy outcomes in the workplace: the case of video display terminal users. AB - In this paper, we review the consecutive methodological steps to follow when assessing clusters of adverse pregnancy outcomes (APO) in the workplace and the decisions to be taken at each step. The example of clusters of APO reported in VDT users in 1979 to 1982 is taken to illustrate each point. It appears that the number of "expected-unexpected" clusters of APO in VDT users has been largely overestimated as compared to observations and that this might be due to inadequate choices in the models used. PMID- 1753310 TI - A study of the interaction of selected drugs and plastic syringes. AB - It is common hospital pharmacy practice to preload syringes with selected drugs and store them ready for use. Because the several components of syringes, (such as barrels, gasket seals, etc.) may vary among manufacturers, there exists the possibility that syringe components of differing provenance might interact e.g., by sorption, with stored drugs to differing degrees. To examine possible interactions, three brands of commercially available syringes were compared to determine what influence, if any, short term storage of injectable solutions might exert on the solutions or the syringes. Four drugs; dexamethasone sodium phosphate, diazepam, diatrizoate meglumine and nitroglycerin USP were individually loaded into 3 mL syringes and stored at temperatures between -20 degrees C and + 25 degrees C for periods from 6 hours to 30 days. The syringes were examined for any gross changes. Drug solutions were analyzed after storage to determine the presence of organic leachates from the syringes and any change from original drug concentration values. No syringes showed gross physical changes after storage with drug solution nor were any drug solutions found to contain leachates on gas chromatographic-mass spectroscopic analysis. Drug concentrations were seen to change following storage, the greatest changes occurring with the highly lipophilic drugs dexamethasone and diazepam. In most instances loss of drug concentration was most rapid at room temperature. Although there were clear differences among the three brands of syringe, no overall pattern emerged which might allow the selection or rejection of one syringe over another for the extemporaneous preloading of the drugs examined. PMID- 1753311 TI - Validation of tangential flow filtration (TFF) systems. PMID- 1753312 TI - Biowaste treatment. AB - Finding a practical solution for effectively managing facility liquid biowaste is a process of deductive reasoning. Many considerations need to be addressed. The liquid effluent must be characterized to determine required capacity, materials of construction and mode of operation of the biowaste treatment system. Federal, state, local and corporate requirements must be identified to determine system operating parameters. Standard technologies can then be reviewed in order to select the most appropriate unit operation for processing the biowaste. Finally, a validation program is developed to demonstrate the efficacy of the treatment system's intended use. This presentation covers typical considerations in developing the design of a biowaste treatment system and validation of acceptance criteria. Several examples from industrial installations are presented. PMID- 1753313 TI - Comparison of bacterial and endotoxin retention by charge-modified sterilizing grade filters during intermittent long-term use. AB - There has been growing concern in recent years about control of bacterial bioburden and endotoxin in pharmaceutical water systems by both the pharmaceutical manufacturers and the Food and Drug Administration (FDA). This concern exists not only for Water for Injection (WFI) systems, but for any water system used in the manufacture of a product which could be affected by the microbial bioburden. In hot WFI systems, bioburden control is assured by keeping the water in the recirculating loops at 80 degrees C. At points of use in these systems, the temperature fluctuates and can be below sanitization temperature for extended periods. On the other hand, in cold water systems [WFI and deionized (DI)], both bioburden and endotoxin control are more difficult. This study shows that sterilizing grade, positively-charged filters can provide absolute bioburden control. In addition, these filters effectively retain high levels of both purified and cell-associated endotoxins over a five month period under severe intermittent system use conditions in a model high-purity water system. This study suggests a solution to the concerns over long-term use of bacterially retentive filters in properly maintained high-purity water systems. PMID- 1753314 TI - Additive model for the evaluation of interactions between aqueous solutes and multi-component container materials. AB - The interaction between aqueous model solutes and various current or potential parenteral solution container materials was studied. Materials examined included composite polymers (plasticized PVC and co-extruded composites) and their individual components. For each material studied (component and composite), the equilibrium interaction constant (Eb), which describes the distribution of a solute between a container and its contained solution, can be related to the solute's octanol-water (Po-w) and hexane-water (Ph-w) partition coefficients via a bimodal Collander-type expression: log Eb = a log Po-w + b log Ph-w + c Additionally, the interaction of the composites was found to be equivalent to the weighted average of the interaction properties of its individual components. That is, Eb,composite = sigma Wi x Eb,i where i represents an individual component of the composite and Wi represents the weight fraction of that component in the composite. The impact of the interaction properties of the components on the behavior of the composites is discussed; thus, for example, the interaction properties exhibited by plasticized PVC is dominated by the behavior of the plasticizer since unplasticized PVC itself exhibits only minimal interaction with aqueous solutes. PMID- 1753315 TI - A novel method of assessment of interfacial adsorption of blood proteins. AB - Interfacial adsorption of proteins can be studied using microscopic surface analysis techniques, and by physical techniques such as interfacial tension measurement. A novel method of surface analysis of adsorbed protein layers is described, which involves interfacial shear rheology of aqueous solutions of proteins. This technique provides information on the structural-mechanical properties of the adsorbed layers which may be related to: the rate of interfacial adsorption, interfacial interactions, and conformational changes in the adsorbed layers. The interfacial shear rheology of aqueous solutions of the blood proteins, bovine serum albumin and human immunoglobulin G was investigated at the air/aqueous interface. The effects of bulk concentration (0.1 to 4.0% w/v) and pH (3 to 8) were investigated, both interfacial viscosity and elasticity values are reported. PMID- 1753316 TI - Reduction of salivary bacteria by pre-procedural rinses with chlorhexidine 0.12%. AB - The purpose of this study was to assess the effect of pre-procedural rinsing (2 consecutive rinses) with 0.12% chlorhexidine gluconate (CHX) on salivary bacteria during scaling and root planing procedures (S&RP). Because blood and debris arising from S&RP could inactivate CHX and decrease its antimicrobial effect, patients were evaluated throughout their appointment. Forty subjects rinsed with either 15 ml of CHX rinse or control (sterile water) for 30 seconds, expectorated and immediately rinsed again for 30 seconds. Unstimulated saliva samples were obtained at baseline (immediately before rinsing), and at 1 minute, 30 minutes, and 60 minutes after baseline. All 30 and 60 minute samples contained visible blood and debris. Samples were immediately diluted in transport fluid containing a CHX-neutralizer and then plated on trypticase soy agar for enumeration of the total aerobic and facultative bacterial load. The dual rinses with 0.12% CHX immediately reduced the salivary bacterial load 97% and this reduction persisted for 60 minutes during S&RP. At 30 minutes and at 60 minutes aerobic bacteria were reduced 77% compared to control, and 96% compared to baseline. CHX was not inactivated by the high organic load (blood and debris) present during the procedure. Pre-procedural rinsing with CHX has a profound and sustained effect on the aerobic and facultative flora of the oral cavity, which may contribute to a variety of clinical benefits. Pre-procedural rinsing may also be of value in protecting patients and dental professionals during dental manipulations. PMID- 1753317 TI - Histologic evaluation of combining tetracycline and allogeneic freeze-dried bone on bone regeneration in experimental defects in baboons. AB - Tetracyclines (TTC) have been used both systemically and locally during periodontal bone grafting procedures, but previous work regarding the effect of TTC on new bone formation has been contradictory. The purpose of this study was to determine if the use of locally applied TTC in combination with freeze-dried bone allografts (FDBA) would enhance bone regeneration in an experimental alveolar bone osseous defect grafting system. Pre-weighed freeze-dried bone allograft particles (300-500 mu diameter) were placed in nylon mesh chambers (250 mu pore size) and rehydrated with either 10 micrograms/ml aqueous TTC or sterile distilled water. Empty chambers were used as further controls. The chambers were placed in the posterior mandible of baboons in surgically created windows. After 3 and 5 weeks, the chambers were retrieved, processed histologically, and analyzed histometrically for new bone formation. The TTC-rehydrated FDBA demonstrated much greater (greater than 5x) new bone formation than the water rehydrated FDBA. These results strongly suggest that locally-applied TTC in combination with FDBA enhances new bone formation in experimental alveolar bone defects. PMID- 1753318 TI - Influence of polishing procedures on sonic scaling root surface roughness. AB - The present in vitro study aimed to evaluate the efficacy of various polishing procedures in reducing root roughness caused by sonic scaling. Proximal root surface areas of extracted, formalin-stored teeth were scaled in a bucco-lingual direction by a sonic scaler. The resulting roughness was measured along the direction of scaling and perpendicular to that direction by a profilometer. The specimens were then split into two groups. Group 1 was polished by an air-powder polishing instrument followed by a rotating rubber cup and chalk; Group 2 was polished by pumice followed by chalk. Root roughness (Ra) was recorded for each step in the procedures. The measurements revealed lower Ra values when the stylus of the profilometer was running perpendicular to the scaling direction, and a weak negative correlation was found when scaling time and Ra values were compared. In both groups Ra values were significantly reduced at each step of the polishing procedures and the terminal result was similar for the groups. Pumice and air-powder polishing gave a similar reduction of the sonic scaling roughness. PMID- 1753319 TI - An in vivo study of dentin sensitivity: the relation of dentin sensitivity and the patency of dentin tubules. AB - Dentin hypersensitivity can be a major problem for periodontal patients. The relationship between dentin hypersensitivity and the patency of dentin tubules in vivo has been established. Thirteen adult patients with teeth scheduled for extraction were selected and a stent fabricated to confirm location of the root surface being examined. Response to a constant air blast was recorded on a numeric pain rating scale (from 0 to 4) during the course of treatment. The tooth surface was initially treated with 0.5 molar EDTA (pH = 7.4), to remove the smear layer and expose tubules. The region was then treated with either a 3% monopotassium-monohydrogen oxalate solution or a 3% sodium chloride solution, both at pH = 2.4. Solutions were prepared to be indistinguishable to the examiner. Response to air was evaluated before and after EDTA treatment and after treatment with a desensitizing agent. The patient was anesthetized and the treated tooth extracted. Specimens were sectioned, critical point dried, sputter coated with gold, and examined under the scanning electron microscope. Photomicrographs were analyzed by computer assisted digital analysis to evaluate the degree of tubule occlusion. Statistical analysis by repeated measures ANOVA for univariate tests of hypothesis for within subject effects showed the sodium chloride solution was more effective in reducing dentin sensitivity than the potassium oxalate solution. Scanning electron micrographic analysis revealed a mean dentin tubule aperture size of 1.720 square microns following EDTA treatment alone, 0.564 square micron following potassium oxalate treatment, and 0.386 square micron following sodium chloride treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753320 TI - In vivo determination of radiographic projection errors produced by a novel filmholder and an x-ray beam manipulator. AB - Subtraction radiography requires radiographs made with identical projection geometry. The purpose of the present investigation was to develop and evaluate a new in vivo method to measure angular radiographic projection error. This included the development of a system for accurate control of the x-ray beam angulation relative to the intraoral film and the evaluation of the in vivo projection errors (equivalent to the "angular difference" between repeated exposures) produced by the new system. A filmholder, an x-ray beam manipulator, and an aiming device were newly constructed. Reference wires were attached for measuring the projection error on the filmholder and on the 22 bicuspids at the sites of investigation in 16 patients. Two exposures using standardized projection conditions were made of each site. The relative position of the reference wires on the duplicate radiographs was used to calculate the angular difference in the direction of the x-ray beam which occurred between the 2 exposures. Triplicate measurements allowed the determination of measurement error. The angular projection errors were measured in a horizontal and vertical direction. The reference wires allowed determination of the angular projection errors relative to the filmholder, relative to the dentition and the angular error due to the repositioning of the filmholder in the patient's mouth. The average projection errors deviated only slightly from zero. The largest deviation registered was -0.11 degrees. This applies to the horizontal and vertical direction and all relationships. The standard deviations varied between 0.403 degrees and 0.697 degrees. This applies to the standard deviation for all relationships in the horizontal, the vertical, and the oblique directions. The measuring error found from the triplicate measurements had a standard deviation of 0.08 degrees to 0.19 degrees depending on the distance between the reference wires. This new system for controlling in vivo projection errors seems to provide highly standardized radiographs in vivo. The new measuring system proved to be accurate enough to measure the in vivo projection errors between repeated radiographs produced with the new filmholder and x-ray beam manipulator. The in vivo errors produced by the new system are markedly smaller than all in vivo and in vitro errors previously reported in the literature. PMID- 1753321 TI - The use of a synthetic skin substitute as a physical barrier to enhance healing in human periodontal furcation defects: a follow-up report. AB - The purpose of this investigation is to compare the clinical response of guided tissue regeneration using a synthetic wound dressing with open flap debridement versus open flap debridement alone in the treatment of human furcation defects. The study group was composed of 19 patients with moderate to advanced adult periodontitis and at least one bilateral pair of Class II molar furcation defects. After the hygiene phase of therapy was completed, measurements were made with calibrated periodontal probes of the clinical attachment levels, probing depths, and soft tissue recession. Paired sites were randomly selected for treatment with either open flap debridement alone (control) or open flap debridement and placement of the synthetic wound dressing over the furcation (experimental). At the time of surgery, measurements of vertical and horizontal open probing attachment were recorded. The dressing was removed 5 to 6 weeks post surgery. The sites were reentered at 6 months to evaluate healing and to repeat all measurements. Statistical comparisons using the Wilcoxon Sign Rank Test were made between the control and experimental sites. The results of 19 pairs of Class II molar furcation defects reveal statistically significant differences between the experimental and control sites in attachment levels, probing depths, and horizontal open probing attachment. These differences were of such small magnitude that they may not be clinically relevant. There were no other significant differences for any other clinical parameter, and none of the furcations in either group was completely closed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753322 TI - Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen. AB - A bone-inductive protein, osteogenin, has been isolated from long bones of humans and offers promise as a grafting material. Studies, however, suggest that osteogenin must be combined with a bone-derived matrix in order to initiate bone differentiation. The purpose of this study was to determine if osteogenin combined with demineralized freeze dried bone allograft (DFDBA), a bone-derived matrix, and with a bovine tendon-derived matrix will enhanced regeneration of intrabony defects in humans. The tendon-derived matrix and DFDBA used alone served as controls. The ability of each material to form a new attachment apparatus was evaluated independently in submerged and nonsubmerged environments in 2 patient populations. Lymphocyte testing was performed to assess development of an immune reaction to osteogenin. The most apical level of calculus on the root served as the histologic reference point to measure regeneration. Biopsies were obtained at 6 months and regeneration was measured histomorphometrically by 2 blinded evaluators. Serial sections from 36 submerged defects in 8 patients and 50 nonsubmerged defects in 6 patients were submitted for statistical analysis. Mean results indicate that osteogenin combined with DFDBA significantly enhanced regeneration of a new attachment apparatus and component tissues in a submerged environment. DFDBA plus osteogenin and DFDBA alone formed significantly more new attachment apparatus and component tissues than either the tendon-derived matrix plus osteogenin or the tendon-derived matrix alone in both submerged and nonsubmerged environments. There were no significant differences between the tendon-derived matrix plus osteogenin and the tendon-derived matrix alone in either the submerged or nonsubmerged environment. Osteogenin does not impair normal lymphocyte blastogenesis at 6 months postsurgical challenge. PMID- 1753323 TI - Guided tissue regeneration for implants placed into extraction sockets: a study in dogs. AB - Twelve 10 mm implants were placed into immediate extraction sockets in dogs. Six implants were isolated with PTFE membranes and 6 sites served as controls. Standardized clinical measurements were taken at test and control sites. At 18 weeks the dogs were anesthetized and flaps were laid for the purpose of obtaining clinical measurements. The average gain of bone around augmented implants was 2.6 mm, while control sites had an average bone gain of 1.0 mm. Ridge width adjacent to augmented sites increased by 1.2 mm and control sites had an increased width of 0.6 mm. Histologic evaluation of test and control specimens showed greater bone formation around augmented implants. Implants augmented with PTFE membranes had clinically significant amounts of bone regeneration when compared with controls. PMID- 1753324 TI - Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs. AB - The purpose of this study was to evaluate the early wound healing events of bone around press-fit titanium implants inserted with and without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin like growth factor (IGF-I). Nine months prior to implant placement all mandibular premolar teeth were extracted in 8 beagle dogs. Subsequently, 40 specially manufactured titanium implants with 2 transverse holes in the apical section were press fit into precise recipient sites in the dogs' mandibles. The dogs were sacrificed at 7 and 21 days following implant placement yielding 12 PDGF-B/IGF-I treated and 8 control (placebo gel or non-treated) implants for each observation period. Coded undecalcified sections were analyzed for: 1) percentage of implant surface in contact with new bone; 2) percentage of peri-implant space filled with new bone; and 3) percentage of implant hole filled with new bone. An analysis of variance was used to determine significant differences among the treatment groups. At 7 days, the percentage of bone fill in the peri-implant spaces and the percentage of implant surface in contact with new bone were both significantly increased in PDGF-B/IGF-I treated sites (P less than 0.01 for both groups). There was less than 1.5% fill of the implant holes in both treated and control sites (no significant differences). At 21 days the percentage of bone fill in the peri implant spaces was significantly increased in the PDGF-B/IGF-I treated sites (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753325 TI - Aging and attitude change. AB - Social psychologists have proposed a variety of different models to account for people's relative openness to attitude change through the life cycle. Two of the most important models are the impressionable years model, which suggests an especially great openness to change among the young, and the lifelong openness model, which suggests that age is unrelated to openness to attitude change. Two studies were conducted to examine the openness of people of varying ages to attitude change. In both studies, the influence of personal experiences with government agencies on attitudes toward government was examined. The attitudes of older people changed as much or more in response to their personal experiences as did those of younger people. These results support the lifelong openness model of attitude change. PMID- 1753326 TI - The accuracy-confidence correlation in eyewitness testimony: limits and extensions of the retrospective self-awareness effect. AB - This research extended Kassin's (1985) finding that retrospective self-awareness (RSA) increases the correlation between eyewitness accuracy and confidence. In Experiment 1, 91 mock witnesses saw a crime, answered questions, made an identification decision, and rated their confidence. RSA increased the accuracy confidence correlation for witnesses who made an identification and for those who were high but not low in public self-consciousness. A 2nd experiment varied accountability and revealed that high accountability increased the accuracy confidence correlation but that the RSA effect occurred even under low accountability conditions. In both studies, observers could not distinguish between accurate and inaccurate witnesses. Together, these findings define the limits of the RSA effect and provide mixed support for a self-perception account of this effect. PMID- 1753327 TI - Affective influences on partner choice: role of mood in social decisions. AB - Does mood influence our information search and decision strategies when choosing a partner? In Experiment 1 (N = 60), sad Ss preferred rewarding to competent partners and remembered information supporting that choice better. In Experiment 2 (N = 96), mood effects on information selectivity, decision speed, and processing strategy in partner choices were found. In Experiment 3 (N = 42), a computerized stimulus presentation revealed mood-induced differences in the latency, self-exposure, and eventual recall of interpersonal information. These results are interpreted as evidence for mood-induced selectivity in information search and decision strategies when making realistic partner choices. The implications of the findings for research on interpersonal relations and for contemporary affect-cognition theories are considered. PMID- 1753328 TI - Socioemotional behavior and satisfaction in marital relationships: a longitudinal study. AB - The interplay between 3 types of socioemotional behavior (affection, sexual interest, and negativity) and marital satisfaction was studied using data from newly married couples followed over 2 years. Affection and negativity (but not sexual interest) were consistently associated cross-sectionally with marital satisfaction. Longitudinal analyses revealed a gender-differentiated pattern suggesting a more complex relationship between satisfaction and marital behavior than previously shown. Negativity, regardless of whether it was expressed by the husband or the wife, was associated with declines in wives' (but not husbands') satisfaction. Wives of husbands who were relatively negative early in marriage became more negative themselves. Wives who were relatively less satisfied early in marriage (but not husbands) were married to spouses who became more negative with time. PMID- 1753329 TI - Do conversational hand gestures communicate? AB - In 5 experiments, male and female undergraduates viewed gestures and tried to select the words that originally accompanied them; read interpretations of gestures' meanings and tried to select the words that originally had accompanied them; tried to recognize gestures they previously had seen, presented either with or without the accompanying speech; and assigned gestures and the accompanying speech to semantic categories. On all 4 tasks, performance was better than chance but markedly inferior to performance when words were used as stimuli. Judgments of a gesture's semantic category were determined principally by the accompanying speech rather than gestural form. It is concluded that although gestures can convey some information, they are not richly informative, and the information they convey is largely redundant with speech. PMID- 1753330 TI - Psychological determinants of health and performance: the tangled web of desirable and undesirable characteristics. AB - Correlations were determined for male (n = 225) and female (n = 242) college students between sets of undesirable personality traits (anxiety, stress reactivity, anger, and alienation) and desirable personality traits (instrumentality, achievement strivings, and optimism measured by the Scheier Carver [1987] Life Orientation Test), and a series of outcome variables related to health (self-reported health complaints and health maintenance behaviors and beliefs) and academic performance (academic expectations and actual grade point average). Significant correlations were found between many of the personality variables and the outcome variables. However, partial correlations revealed different relationships for the various criteria. With other variables held constant, health complaints were related to several undesirable characteristics, whereas health maintenance behaviors and beliefs were related to several desirable attributes. Only achievement strivings made an independent contribution in both sexes to the 2 measures of academic performance. The theoretical and methodological wisdom of using measures of multiple personality constructs and outcome variables is discussed. PMID- 1753331 TI - Nonverbal display of emotion in public and in private: self-monitoring, personality, and expressive cues. AB - Individual differences in the expression and regulation of emotion are important components of social skill. The present study focused on the concealing of spontaneous expressions of happiness after winning in a competitive situation against peers. In a repeated measures design, spontaneous expressive behaviors in response to triumph were secretly videotaped when Ss (N = 38) were alone in a room and when they were with 2 fellow competitors (confederates). Edited tapes were analyzed by naive raters and trained coders. As predicted, the social context strongly influenced the expressive behaviors of Ss, providing support for a social inhibition effect. More important, the self-monitoring construct (Snyder, 1987) was helpful in explaining individual differences in expressive regulation, with high self-monitors being successful at hiding their happiness when appropriate; and they did so in particular ways. Low self-monitors did not conceal their emotions. Other findings with regard to personality and sex differences were also uncovered. PMID- 1753332 TI - Factor influencing suicide intent in gay and bisexual suicide ideators: differing models for men with and without human immunodeficiency virus. AB - Of 778 gay and bisexual men (none with acquired immunodeficiency syndrome [AIDS]), 27% (n = 212) reported suicidal ideation over the previous 6 months. Covariance structure models were used to explore predictors of suicide intent among (n = 112) suicide ideators with (n = 100) and without (n = 112) human immunodeficiency virus (HIV). Current AIDS-related stressors (deaths and illnesses and perceived AIDS risk) and past levels of adaptive functioning (social isolation and depression) were significantly more powerful predictors of suicide intent among HIV-positive than among HIV-negative ideators. Biological AIDS risk predicted neither suicide intent, current distress, nor perceived AIDS risk. Pathways to suicide intent appear to be psychologically, rather than biologically, mediated. Among HIV-positive ideators, AIDS-related death and illness events predicted suicide intent but not current distress symptoms. Some suicidal ideation in response to AIDS-related events may be an effort to cope rather than a manifestation of psychological distress. PMID- 1753333 TI - Constructive thinking and coping with laboratory-induced stress. AB - In a laboratory stress test, poor constructive thinkers produced more negative affective and cognitive responses in all experimental periods and a greater increase in such responses in the stress period than did good constructive thinkers. The groups differed in physiological arousal in the recovery period but not in the stress period. Stressor-instigated negative thoughts and spontaneous negative thoughts produced different patterns of relations with variables measured in the laboratory and with symptoms reported in everyday life. Discriminating patterns of relations were found between measures of cognition and affect in the laboratory and self-reported emotional, physical, and behavioral symptoms in everyday life. The results help explain the relation between maladaptive automatic thinking, on the one hand, and elevated physiological arousal and emotional, physical, and behavioral symptoms, on the other. PMID- 1753334 TI - Coping success and its relationship to psychological distress for older adults. AB - The role of coping success on psychosocial distress was investigated in 147 older adults who experienced a major health problem and 82 older adults who reported a major loss in the past 6 months. Home interviews provided data on satisfaction with coping efforts and negative changes associated with events. Significant predictors of coping success were identified and controlled for in subsequent analyses predicting mental health. Efficacy in coping with loss was associated with less psychological distress. Coping efficacy interacted with coping efforts in predicting distress for those with health downturns; efficacy in coping was associated with less distress only for those who were actively engaged in coping. Analyses of longitudinal data replicated the cross-sectional findings for coping with loss. PMID- 1753335 TI - Differentiated additive androgyny model: relations between masculinity, femininity, and multiple dimensions of self-concept. AB - Masculinity (M) and femininity (F) were related to multiple dimensions of self concept in 2 large studies. Androgyny theory predicts that M and F contribute positively to self-concept, but the effect of F has been nil in research using global self measures. Here, consistent with the new differentiated additive model, the relative contribution of M and F varied substantially, depending on the area of self-concept; F contributed more positively to self-concept facets that were more stereotypically feminine. Support for the model was consistent across self-responses and responses by significant others (Study 1) and across 5 age groups in early-to-middle adolescence (Study 2). PMID- 1753336 TI - Relation between social problem-solving ability and subsequent level of psychological stress in college students. AB - A prospective design was used to examine the relation between social problem solving ability and later psychological stress in college students during the first semester of the academic year. A new social problem-solving inventory measured not only general ability, but also more specific components of the problem-solving process (e.g., problem orientation, problem-solving skills; D'Zurilla & Nezu, 1990). The results of a hierarchical multiple regression analysis showed that general problem-solving ability was negatively related to later stress, even after prior stress level and number of life problems were controlled. More specific analyses indicated that subjects' problem orientation was a better predictor of stress than their problem-solving skills. Results are discussed in terms of the possible stress-reducing effects of perceived control and successful problem resolution. PMID- 1753337 TI - Postexposure chemoprophylaxis with ZDV or ZDV combined with interferon-alpha: failure after inoculating rhesus monkeys with a high dose of SIV. AB - Presently, no information is available regarding the efficacy of chemoprophylaxis in controlled human trials following accidental exposure to the human immunodeficiency virus (HIV). Using the closely related simian immunodeficiency virus (SIV) in rhesus monkeys, which develop a disease closely resembling human AIDS, we tested the efficacy of either single-agent 3'-azido-3'-deoxythymidine (ZDV) or the combination of ZDV plus recombinant human interferon-alpha (IFN alpha). Treatment was started 3 h following inoculation of a high dose of SIV and continued for 21 days. SIV-inoculated control animals remained untreated. Virus was recovered from all monkeys on day 8, and by week 7 all had seroconverted. In contrast to monkeys treated with ZDV alone, animals given combination therapy had lower levels of p27 gag antigen compared to untreated controls on day 8 (p = 0.043). We conclude that neither treatment regimen could prevent infection after high-dose virus exposure; however, combination therapy may have depressed the level of virus replication more effectively than ZDV alone. PMID- 1753338 TI - Porphyria cutanea tarda in human immunodeficiency virus-seropositive men: case report and literature review. AB - Porphyria cutanea tarda (PCT) is a disorder of heme synthesis characterized by (a) a diminished activity of uroporphyrinogen decarboxylase biochemically and (b) cutaneous lesions secondary to a delayed type of photosensitivity clinically. A human immunodeficiency virus (HIV)-infected patient with PCT is reported and the world literature is reviewed. To date, 17 HIV-seropositive men with PCT have been described. The initial appearance of PCT occurred before or concurrent with the diagnosis of HIV infection in 71% of these individuals (12 men). The median age at onset of PCT was 36 years (range of 20 to 69 years); the median age for the detection of HIV infection was 35 years (range of less than 20 to 71 years). All of these patients had elevated levels of urine porphyrins and blisters on their dorsal hands. Abnormal liver function tests, erosions, hyperpigmentation, hypertrichosis, and skin fragility were also present in some of the men. Polycythemia, serologic evidence of increased iron stores, scarring, milia, and sclerodermoid changes were rarely observed. Successful therapeutic approaches for PCT in men with HIV infection included (a) elimination of PCT-precipitating agents, (b) avoidance of sun exposure, and (c) periodic phlebotomy. Multiple hypotheses for an etiologic role of the HIV and/or an HIV-associated infection, directly or indirectly, in the pathogenesis of PCT in HIV-seropositive men have been suggested. PMID- 1753339 TI - Sequential measurement of beta 2-microglobulin levels, p24 antigen levels, and antibody titers following transplantation of a human immunodeficiency virus infected kidney allograft. AB - A renal allograft recipient developed symptoms suggestive of AIDS. Serological studies revealed that the donor was positive for human immunodeficiency virus (HIV). Retrospective testing of stored sequential serum samples showed that the recipient was negative for HIV pretransplant; anti-p24 and anti-p41 antibodies appeared 10 and 49 days posttransplant, respectively. The recipient's serum beta 2-microglobulin levels were elevated 14 days posttransplant, with normal renal function, 35 days before the detection of anti-p24 antibody. p24 Antigen was detected for the first time 21 days posttransplant. In addition to p24 antigen, elevated serum beta 2-microglobulins may be a useful marker for HIV infection prior to seroconversion. PMID- 1753340 TI - Association of vitamin B6 status with parameters of immune function in early HIV 1 infection. AB - Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function. PMID- 1753341 TI - The response of American women to the threat of AIDS and other sexually transmitted diseases. AB - Using data from the National Survey of Family Growth, we observe that large numbers of American women say that they are responding to the rising danger of AIDS and other sexually transmitted diseases. Among the changes reported in the 1988 National Survey of Family Growth are use of condoms, sexual relations with fewer partners, reduced frequency of sexual intercourse, changes in specific sexual activities, and avoidance of sex with unknown men, bisexual men, and intravenous drug users. Interviews with a sample of the 51 million sexually active women aged 15-44 in the United States show that 28% report either that they have adopted less hazardous sexual practices or that their partners have used condoms to prevent disease. Among women exposed to higher risk of disease, the response is even greater: among unmarried women with five or more lifetime partners, 65% report modified behavior or condom use. Most of these changes occurred after the women heard of AIDS. However, there are still many women who report doing nothing to protect themselves against infection despite sexual and contraceptive behavior that appears to put them at high risk. PMID- 1753342 TI - HIV infection and AIDS risk behaviors among intravenous drug users entering methadone treatment in selected U.S. cities. AB - To assess trends in HIV infection and AIDS risk behaviors among intravenous drug users (IVDUs), a series of nonblinded point-prevalence surveys was conducted with admissions to methadone treatment in seven areas, including New York City; Trenton and Asbury Park, New Jersey; Baltimore; Chicago; San Antonio, Texas; and Los Angeles County between February and December 1987 (n = 713), January and June 1988 (n = 1,089), July and December 1988 (n = 932), and January and June 1989 (n = 1,110). Over the 2-year period, significant changes in HIV seropositivity levels were found in only one of the seven cities (Chicago, with levels increasing from 8.4 to 14.7%). High levels of AIDS risk behaviors (frequency of injection, needle sharing, needle cleaning, and use of shooting galleries) were found in all cities. Comparisons of trends in recent risk behaviors (past year) within cities suggest that relatively little reduction in AIDS risk behaviors had occurred during the study. PMID- 1753343 TI - Risk factors for HIV-2 infection in Guinea-Bissau. AB - To define the epidemiology of HIV-2 infection, we conducted a case-control study among hospitalized patients at an acute care hospital in Bissau, Guinea-Bissau, a country with endemic HIV-2 infection. Among 128 patients with various diagnoses, 23 (18%) were positive for HIV-2 by ELISA and Western blot. One of these patients was serologically reactive for HIV-1 also, but PCR and viral culture revealed the presence of HIV-2 only. To study risk factors, behaviors, and AIDS knowledge related to the acquisition of HIV infection, 22 HIV-2-seropositive and 21 seronegative hospitalized patients were given a physical examination and administered a questionnaire. Among women, transfusion was associated with HIV-2 infection (OR = 14.4, p = 0.02); among men, sex with a prostitute was the principal risk factor (OR = undefined, p = 0.02). Although 79% of HIV-infected patients and controls had heard of AIDS, only 17% of all study participants and 50% of males reporting sex with prostitutes had used condoms in the previous year. These data suggest that the risk factors for HIV-2 infection are similar to those for HIV-1 and support previous studies showing that HIV-2 is the predominant HIV in Guinea-Bissau. Efforts to decrease transmission of HIV-2 should include screening for HIV-2 in blood for transfusion in endemic areas (now done in Bissau) and education about the risk of sexual transmission. PMID- 1753344 TI - Triple therapy with vinblastine, interferon-alpha 2a and zidovudine for AIDS related Kaposi's sarcoma. PMID- 1753345 TI - HIV-related autoimmune hemolytic anemia: good response to zidovudine. PMID- 1753346 TI - Community-acquired pneumonia with penicillin-resistant pneumococci in a patient with AIDS. PMID- 1753347 TI - HIV-1 transmission by a heterosexual man treated with zidovudine. PMID- 1753348 TI - Oral Candida and Enterobacteriaceae in HIV-1 infection: correlation with clinical candidiasis and antimycotic therapy. AB - Oral swabs of 73 HIV-1 infected men (32 under conditions of antimycotic treatment (43.8%)) and 58 controls were cultured for Candida species and Enterobacteriaceae. In Group A without antimycotics, yeasts were isolated from 35/41 swabs (85.4%) (range 2 x 10(1) - 4 x 10(6) cfu/ml). In Group B with antimycotics, yeasts were cultured from 27/32 swabs (84.4%) (4 x 10(1) - 1 x 10(6) cfu/ml). Oral Enterobacteriaceae (o.e.) were grown from 22% of the swabs of both Group A (2 x 10(1) - 2 x 10(6) cfu/ml) and Group B (4 x 10(1) - 1.6 x 10(6) cfu/ml). Growth of o.e. and yeasts (2 x 10(3) - 4 x 10(6) cfu/ml). Correlation between yeasts and o.e. were isolated in 14% (2 x 10(1) - 6.4 x 10(6) cfu/ml). Correlation between yeasts species to local and systemic treatment deserves further investigations. PMID- 1753349 TI - Recurrent aphthous ulceration and food sensitivity. AB - Forty patients with recurrent aphthous ulceration (RAU) were investigated to ascertain the possibility of food sensitivity being a significant precipitating factor in their recurrent oral ulceration. All patients were hematologically normal and did not respond to vitamin B1 and B6 therapy. Patch testing (Standard European Series) was undertaken in 21 patients. Twenty patients showed a positive reaction to a number of substances which were considered clinically relevant. Professional advice on avoidance of the allergen was given, resulting in an improvement in eighteen patients. It is concluded that food sensitivity and allergies to other substances should be considered as an etiologic factor in hematologically normal patients with recurrent oral ulceration. PMID- 1753350 TI - Gliadin antibodies identify gluten-sensitive oral ulceration in the absence of villous atrophy. AB - This study demonstrates gluten-sensitive recurrent oral ulceration (ROU) in the absence of gastrointestinal abnormalities which is associated with a humoral response to wheat protein. Ten patients with severe ROU were investigated; all had normal small intestinal biopsies. Four patients had raised levels of antibodies to alpha gliadin, a wheat protein fraction; in three of these four, the ulceration remitted on treatment with a gluten-free diet (G.F.D.) and relapsed on gluten challenge. None of the remaining six patients had raised alpha gliadin antibody (AGA) levels and none responded to G.F.D. Thus raised AGA levels can be used to identify patients with ROU who are likely to respond to a GFD. PMID- 1753351 TI - Creatine kinase isoenzymes activity in serum and buccal pouch tissue of hamsters during DMBA-induced squamous cell carcinogenesis. AB - The sequential changes of creatine kinase (CK) isoenzyme activity in serum and hamster buccal pouch tissue (HBPT) of normal, premalignant, and malignant stages during 13 wk of DMBA induced hamster buccal pouch squamous cell carcinogenesis, were studied. We found that the total CK activity in both serum and HBPT of the DMBA painted groups increased during the premalignant period (3-7 wk), with the peak being at 7 wk, while declining in the malignant period (9-13 wk). No significant difference in the serum and HBPT CK-MM, CK-MB and CK-BB activity, in DMBA-induced carcinogenesis, could be established. However, the macro CK type 2 (MCK-2), a cathodically migrating atypical creatine kinase isoenzyme, initially appeared in the sera and tissues of the 3rd wk DMBA-treated group. Its activity gradually increased during the premalignant and malignant stages, paralleling the increasing number of DMBA applications. There was a correlation between the degree of differentiation, and the size and number of the induced tumors with MCK 2. No MCK-2 could be detected in any of the sera or tissues of the control, nor in the 1st wk DMBA-treated group. We propose that MCK-2 is a potential tumor marker in oral malignancy and its presence may provide valuable information for early diagnosis of a possibly premalignant transforming oral lesion. PMID- 1753352 TI - An investigation of parotid gland function and histopathology in autoimmune disease-prone mice of different age groups. AB - This work aimed to characterize parotid gland function in autoimmune disease prone murine strains (MRL/n, MRL/l and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/l mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjogren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age. PMID- 1753353 TI - Healing of pulp exposures: an ultrastructural study. AB - The fine structure of tissue changes during the first 14 days following pulp exposure and capping with a hard setting Ca(OH)2 cement has been studied. The early changes included hemorrhage and moderate inflammation which were largely resolved during the first week. During the second week differentiation of cells occurred at the wound surface. These cells had the characteristic features of odontoblasts and formed a predentin-like collagen matrix. The capping material was closely adapted to cellular structures at the wound surface or to the predentin-like matrix at all observation periods. Dentin fragments displaced into the pulp tissue during cavity preparation, acted as sites for pulp stone formation. PMID- 1753354 TI - Leukocytoclastic vasculitis (anaphylactoid purpura): a unique occurrence in the oral cavity. AB - Leukocytoclastic vasculitis, immune complex disorder (type III), is a skin disease with both an acute form characterized by bullae, vesicles and ulcerations, and a chronic form characterized by petechiae, macules and ulcerations. The disease presents certain systemic features including diffuse or focal glomerulonephritis and renal failure. The histopathologic characteristics of leukocytoclastic vasculitis in the skin appear primarily in small blood vessels and consist of an infiltration of inflammatory cells, leukoclasis, swelling of endothelial cells, occlusion of blood vessels, accumulation of fibrin and fibrinoid degeneration, as well as the presence of immune complexes in and around blood vessel walls. Although leukocytoclastic vasculitis is described as several diseases which can spread systemically, including the gastrointestinal tract and the kidneys, the manifestations of the disease in the oral cavity have not yet been reported. The present paper reports unique oral lesions in a 38-yr old woman, diagnosed as leukocytoclastic vasculitis, without any accompanying skin or systemic lesions. PMID- 1753355 TI - Epstein syndrome: oral lesions in a patient with nephropathy, deafness and thrombocytopenia. AB - Epstein syndrome is a rare dominantly inherited disorder in which the main features are nephritis, deafness and macrothrombocytopathic thrombocytopenia. A case with oral haemorrhage and purpuric lesions is reported. This appears to be the first report of this syndrome in the dental literature. PMID- 1753356 TI - Rieger's syndrome. AB - Rieger's syndrome which is a congenital progressive, autosomally dominant, ophthalmic anomaly has certain associated somatic dentofacial and systemic features. These extra dentofacial and systemic findings can play very important role in diagnosing this syndrome so as to prevent the ocular complications. This article reports such a case in a 20-yr-old woman and discusses somatic features along with the clinical importance of early diagnosis. PMID- 1753358 TI - [Armageddon]. PMID- 1753357 TI - Ameloblastic fibro-odontomas in animals. PMID- 1753359 TI - [Echo-endoscopy and cancer of the esophagus]. PMID- 1753360 TI - [Scapulo-humeral periarthritis. From the clinical to the imaging aspect]. PMID- 1753361 TI - [Gradient echo sequences in the diagnosis of inferior vena cava thrombosis]. AB - The capability for studying noninvasively vessels has been dramatically improved with the use of gradient echo sequences. Twenty-one patients presenting a suspected inferior vena cava obstruction on cavography underwent MR examination with axial, sagittal and coronal gradient echo images. Eighteen patients were also imaged with ultrasound and/or CT. Gradient echo sequences visualized a thrombus in 19 cases and a normal vein in the remaining 2 cases. The potential MR pitfalls are illustrated and the two cases of false positive on cavography are discussed. Gradient echo sequences allow a fast and performant examination of the vessels. PMID- 1753362 TI - [Disk highlighting after injection in MRI. Macroscopy and histology of 25 postoperative recurrences]. AB - 400 cases of failed back syndrome were examined with MRI in a prospective study (SE w Rho and T2, SE wT1 before and after injection of paramagnetic contrast agent in axial and sagittal planes). After second time surgery, 70 cases of herniated disks were found. 25 herniated disks were studied in microscopy and results correlated with enhanced herniated disks. Authors describe 4 types of enhancement: veinous plexus (5/24), inflammatory or granulomatous tissue (12/24), degenerative disc with fibrosis (5/24) and osteophytosis (2/24). The criterions of each pattern are described. PMID- 1753363 TI - [Intradural metastases of visceral cancers. MRI aspects. Apropos of 2 cases]. AB - The authors report two cases of intradural metastasis: a man with bronchopulmonary cancer suffering from left L5 sciatic pain and a woman with breast cancer whose examination shows motor weakness of both legs. CT was negative in the first case. Gadolinium injection on T1 sequence shows in the first case small nodular lesions along the roots of cauda equina and in the second case linear enhancements around the spine, at different levels. These aspects are the most frequently reported. MRI is an innocuous and the most sensitive technic for such lesions. An early diagnosis improves the functional prognosis. Despite of radiotherapy and chemotherapy, vital prognosis remains bad because of widespread of the intradural lesions and their frequent association with cerebral metastasis. PMID- 1753364 TI - [Color Doppler in breast tumor pathology]. AB - Colour Doppler findings in a series of 63 cases of breast tumours and 19 cases of lymph node enlargements are reported. Colour Doppler signals of abnormal flow are found in 68.5 percent of the cancers, in 42.8 percent of metastatic lymph nodes and in 10 percent of benign lesions. There was bidirectional flow in 80 percent of all the cases. In cases of malignant tumours, the signal was correlated with the size and location of the lesions most often found peripherally. Presently, this technique appears to be of little value in determining whether a primary malignant tumour of the breast is malignant or benign. It does appear to be useful, first to follow-up cancers during initial chemotherapy (partial regression of the signal and of tumour volume) and secondly, in the diagnosis of metastatic lymph nodes with a specificity of 100 percent in our series. Colour Doppler is on the contrary difficult to interprete after conservative treatment of breast cancer because of post-radiotherapy tissue remodelling. PMID- 1753365 TI - [Primary sarcoma of the pulmonary artery]. AB - On the basis of one personal case of leiomyosarcoma, the various anatomicoclinical features of sarcomas of the pulmonary artery are summed up. They most often produce a picture of severe pulmonary embolism that is resistant to all treatments; the lesion most often is a hilar mass without any associated bronchoscopic abnormality. Angiograms are not always easily interpreted, and the modern imaging techniques (ultrasound, computed tomography, and above all MRI) can best lead to the preoperative diagnosis, although this lesion is unfrequent. PMID- 1753366 TI - [X-ray computed tomography in the surveillance of the course of acute pancreatitis. Values of a new classification of inflammatory lesions]. AB - 378 tomodensitometric investigations were performed in cases of acute pancreatitis. The evolution of inflammatory lesions were analyzed with special attention to tissue aggressive inflammation in order to recognize early signs of gravity on CAT scans. Pancreatic lesions less than 15 mm in diameter called "hypodense islets-1" are compatible with oedematous lesions while lesions greater than 15 mm in diameter ("hypodense islets-2") are characteristic of developing necrosis. Tissue aggressive inflammatory lesions were classified in five grades retrospectively and showed that the incidence of abcesses was greater in grade II (76.5%) than in grade I lesions (11.75%). PMID- 1753367 TI - [Localized cancer of the prostate. Correlation between MRI and anatomo pathological results after radical prostatectomy]. AB - Magnetic Resonance Imaging of 20 patients with local prostatic carcinoma was correlated with pathological findings after radical prostatectomy. The tumor was always seen with an hyposignal, associated in 6 cases with benign prostatic hyperplasia. Extracapsular extension was correctly evaluated (17 cases/20). There were 6 false positive diagnosis of seminal vesicles extension among 40 cases because of an hyposignal in intact vesicles and one false negative diagnosis. Magnetic Resonance Imaging is a good exam to appreciate loco-regional extension of prostatic carcinoma. PMID- 1753368 TI - [Imaging of non-functional retroperitoneal paragangliomas. Apropos of a case]. AB - The non functional extraperitoneal paragangliomas are rare tumors (less than 50 cases reported). We report a case with ultrasound and CT scan imaging. The tumor is usually large with important necrotic areas leading to a cystic aspect. The malignant tumors more frequent than the benign tumors present with a regional extension and delayed metastasis. PMID- 1753369 TI - Free microvascular fibular transfer for idiopathic femoral head necrosis: long term follow-up. AB - The authors discuss free microvascular bone transfers in general, and propose a new classification for idiopathic femoral head necrosis. They then present a technique they have been using for 11 years, with the goals of providing both mechanical support and an improved blood supply to the femoral head. This technique involves clearing the necrotic area of the femoral head, filling the area with cancellous bone taken from the greater and lesser trochanters, and transferring a fibular microvascular graft. The approach is transtrochanteric and spares the capsule. Vascular anastomosis is done with the lateral branches of the deep femoral artery, sparing the anterior circumflex artery which is important to the blood supply of the femoral head. Forty-five cases have been surgically managed over 11 years. Eighteen cases with follow-up longer than five years were analyzed, providing an 84 percent successful outcome with both very good and good results. PMID- 1753370 TI - Nerve regeneration in rat composite-tissue allografts. AB - Reinnervation of composite-tissue allografts was examined in a rat hind-limb transplant model under Cyclosporin A (CyA) immunosuppression. Two groups of animals were studied. Group 1 consisted of 10 composite-tissue allografts using inbred Fisher rats (F344) as recipients and inbred Lewis rats (LEW) as donors. Recipient animals received 15 mg/kg/day CyA subcutaneously for three weeks and then twice weekly for three months. Group 2 consisted of 10 composite-tissue isografts undergoing no immunosuppression, and using F344 as both donors and recipients. Eight months after operation, electromyographic, histologic, and morphometric assessments of nerve regeneration were made. There were no significant electromyographic differences between these two experimental groups in amplitude and conduction velocity, but the levels were lower than in controls. The histologic patterns of nerve regeneration within the composite-tissue transfers were similar in the two groups. However, the fiber population in the regenerated nerves in the two groups was different from that in the normal sciatic nerve. This study confirmed the reinnervation of composite-tissue allografts under CyA immunosuppression. The quality of regeneration in allografts was similar to that in isografts, but the histologic and electromyographic properties of regenerated nerves were different from those of normal sciatic nerves. PMID- 1753371 TI - The use of a new perfusate in experimental microvascular flaps: a threefold increase in ischemic tolerance. AB - The benefit of perfusion washout in both experimental and clinical skin flaps has long been debated. By perfusing ischemic rat pedicled flaps with UW solution, a recently developed, high-molecular-weight, organ-preservation medium, a 170 percent increase in the critical ischemia time of treated versus untreated control flaps was demonstrated. Sixty rats were used in this study. A 3- x 6-cm unilateral abdominal skin flap based on the superficial inferior epigastric artery and vein was raised. The flaps were divided into three groups: Group 1 (control--no perfusion washout (n = 15); Group 2 (LR)--perfusion washout with lactated Ringer's solution (n = 15); Group 3 (UW)--perfusion washout with UW solution (n = 30). Flaps were subjected to varying periods of ischemia, ranging between 8 and 30 hr. The primary ischemia time at which 50 percent of the flaps survived clinically was 10 hr for Group 1, 15 hr for Group 2, and 27 hr for Group 3. The differences between the survival rates for flaps in Groups 1, 2, and 3 were statistically significant (p less than .0005). By bathing the vascular and parenchymal cells in an impermeant preservation solution, it was hypothesized that cellular swelling would be inhibited, thereby significantly improving a skin flap's tolerance to warm ischemia. Furthermore, after reviewing the pertinent literature, it is evident that the primary critical ischemia time of 27 hr is the highest reported to date for the normothermic experimental rat pedicled flap. Clinical application of these findings, as well as the need for further studies, are discussed. PMID- 1753372 TI - Stented laser-welded vasovasostomy in the rat: comparison of Nd:YAG and CO2 lasers. AB - In 54 male Sprague-Dawley rats, 108 vasovasostomies were performed. Sutureless laser welding with the assistance of a removable stent was done using a CO2- and an Nd:YAG-laser system. Conventional two-layer microsurgical anastomoses served as controls. The Nd:YAG laser resulted in significantly lower patency rates, with a higher percentage of sperm granulomas; the CO2 laser produced results equivalent to conventional suturing. Sutureless laser welding utilizing a removable stent proved to be a time- and cost-saving procedure for vasovasostomies in the rat. PMID- 1753373 TI - A composite neuro-teno-cutaneous forearm flap in the one-stage reconstruction of a large defect of the soft tissue around the ankle. AB - The vascular anatomy of the radial forearm flap, incorporating the brachioradialis and palmaris tendons together with the superficial radial nerve in 20 fresh cadavers, is described. The radial artery in the cadaveric forearm was irrigated and injected with blue latex. The number and distribution of the cutaneous branches supplying the skin, brachioradialis tendon, palmaris tendon, and superficial radial nerve, were then documented in relation to the distance from the radiocarpal joint. The radial artery was found to provide adequate blood supply to the above structures. This flap has been used as a composite neuro-teno cutaneous flap to resurface a large defect involving tendon, nerve, and skin loss in the ankle and the foot as a one-stage procedure. This technique avoids multiple-staged operations and thus shortens the convalescent period in rehabilitation of severely traumatized limbs. PMID- 1753374 TI - Complications of the free-flap donor site from a community hospital perspective. AB - Techniques for achieving appropriate wound healing with minimal aesthetic or functional deformity of the microsurgical flap donor site are often assumed to be of minor importance or blatantly overlooked. Surprisingly, an analysis of 115 consecutive free-tissue transfers by a single surgeon within a community hospital setting, revealed an overall donor-site complication rate of 31 percent, with significant disability from major complications occurring in 10 percent of cases. Recognition of the projected morbidity of alternative donor sites therefore deserves scrutiny, with the same intensity as does consideration for flap selection, previously done solely to fulfill the requirements of the recipient site. While flap viability has previously been the criterion for success, the future dictates that morbidity at the donor site be an equally important consideration. PMID- 1753375 TI - Timing relationships for secondary ischemia in rodents: the effect of arteriovenous obstruction. AB - The first ischemic insult a tissue suffers is primary (1 degree) ischemia. A second ischemic episode, such as thrombosis after free tissue transfer, may be regarded as secondary (2 degrees) ischemia. Timing relationships were studied in a rodent epigastric-flap model. In a first experiment, the interval between 1 degree ischemia and 2 degrees ischemia was varied. Flaps which had 2 degrees ischemia 12 and 36 hr after the 1 degree episode, had decreased ischemic tolerance, compared with 1 degree ischemic flaps; 2 degrees ischemic flaps, after an interval of 72 hr, had an ischemic tolerance similar to 1 degree ischemic flaps. In a second experiment, the length of the 1 degree ischemia was varied. It was found that as little as 5 min of 1 degree ischemia significantly decreased the subsequent tolerance of 2 degrees ischemia. The possible clinical significance of these results is discussed. PMID- 1753376 TI - One-stage repair of both skin and tendon digital defects using the arterialized venous flap with palmaris longus tendon. AB - A novel technique of composite free-flap and tendon transfer is introduced and used in four patients to repair complicated finger injuries involving loss of skin and tendon. This is a one-stage procedure, providing unbulky, high-quality tissue. Although the final range of motion was disappointing, with an average of 10 degrees, there is justification for further clinical trials in patients with loss of skin and tendon in the digits. PMID- 1753377 TI - End-to-side-anastomosis in the dog using the 3M precise microvascular anastomotic system: a comparative study. AB - In this study, the patency rates, microscopic characteristics, and intraluminal dimensions of end-to-side anastomoses in the dog were compared with those of a conventional interrupted suturing technique, using the 3M precise microvascular anastomotic system. The anastomoses included end-to-side repairs of the saphenous artery to the femoral artery, as well as the saphenous vein to the femoral vein. The patency and microscopic characteristics of the two techniques were similar, but the mechanical coupling system required much less time than the suture technique to complete the vascular anastomosis. PMID- 1753379 TI - Affinity and conformation of the estrogen receptor when bound to single-stranded vs. double-stranded nonspecific DNA. AB - The affinity of the hormone-bound estrogen receptor for single-stranded and double-stranded DNA was compared using isocratic elution chromatography. The receptor bound single-stranded DNA with a two-fold higher affinity than double stranded DNA (17.9 x 10(4) M-1 vs. 9.1 x 10(4) M-1) at 0.2 M KCl. The same number of ions were released when the receptor bound either single-stranded or double stranded DNA (11.8 vs. 10.6, respectively). These results indicate the hormone bound estrogen receptor has no strong preference for single-stranded vs. double stranded nonspecific DNA, and has a similar conformation when bound to either form of DNA at physiological salt concentrations. PMID- 1753378 TI - Initial characterization of the nicotinic acetylcholine receptors in rat hippocampal neurons. AB - The properties of the neuronal nicotinic acetylcholine receptor in primary cultures of hippocampal cells from fetal rats (17-18 days gestation) were studied using the whole-cell patch-clamp technique in Na(+)-external, Cs(+)-internal and nominally Mg(2+)-free solutions. The nicotinic agonists acetylcholine, (+)anatoxin-a, and (-) and (+)nicotine all evoked inward whole-cell currents in hippocampal neurons that were voltage clamped near their resting potentials. Sensitivity to (+)anatoxin-a was first detected at around day 6, and thereafter the magnitude of the response increased as a function of number of days in culture up to about 40 days. The whole-cell current waveforms consisted of more than one peak whose relative amplitude depended on the agonist concentration. These currents were reversibly blocked by micromolar concentrations of d tubocurarine, mecamylamine, and dihydro-beta-erythroidine. At nanomolar concentrations, neuronal bungarotoxin, alpha-bungarotoxin and alpha-cobratoxin caused an irreversible blockade of the currents but they were unaffected by tetrodotoxin, atropine, DL-2-amino-5-phosphonovaleric acid, Mg2+, and 6,7 dinitroquinoxaline-2,3-dione. In addition, the currents were also blocked in a reversible manner by methyllycaconitine at picomolar concentration. The current voltage plots elicited by both (+)anatoxin-a and acetylcholine revealed larger inward currents and smaller or no outward currents. The present results demonstrate the existence of an inwardly rectifying, snake neurotoxin-sensitive functional nicotinic acetylcholine receptor ion channel in rat hippocampal neurons. PMID- 1753380 TI - Sulfhydryl reagents alter epidermal growth factor receptor affinity and association with the cytoskeleton. AB - Sulfhydryl (SH) reagents are known to influence the characteristics of many ligand-receptor systems. The SH reagent N-ethylmaleimide has been demonstrated to interact with EGF receptors, and to inhibit EGF receptor kinase activity. The data presented in this paper concern the effect of SH reagents on two intriguing features of the EGF receptor system, namely the presence of low and high affinity EGF binding sites, and the interaction of EGF receptors with the cytoskeleton. SH reagents were observed to induce a disappearance of high, but not low, affinity EGF receptors from the cell surface, and an increase in receptor-cytoskeleton interaction. Comparison of the effects of membrane-permeant and membrane impermeant SH reagents on wild type and structurally modified EGF receptors suggested that sulfhydryl groups on the cytoplasmic, rather than the extracellular, receptor domain are involved. This indicates that the cytoplasmic domain of the EGF receptor plays a role in the high affinity binding of EGF, and in the interaction of EGF receptors with the cytoskeleton. Experiments with an anti-EGF receptor antibody that specifically blocks the binding of EGF to low affinity receptors indicated that EGF induces a shift in the EGF receptor from low to high affinity. SH reagents probably affect EGF binding by inhibiting this EGF-induced receptor conversion. PMID- 1753381 TI - Estrone modulates the EGF receptor in the liver of db/db mouse. AB - The genetically diabetic db/db mouse is an excellent model to study the effect of diabetes on hormone receptors. The decrease of EGF binding sites could be detected in the hepatic microsomes of diabetic mice as early as 3 weeks of age. In addition, there was an age-related decrease in the autophosphorylating activity of EGF receptor isolated from the liver of diabetic mice. Estrone feeding (0.005%) partially restored this autophosphorylating activity. Northern blot analysis showed that the hepatic EGF receptor transcripts were dramatically decreased during the progression of diabetes and could be reversed by estrone feeding. Transfection experiments carried out on HepG2 cells using EGF receptor promoter (pERCAT-6) demonstrated that addition of 2 x 10(-8) M estrone stimulated chloramphenicol acetyltransferase activity. Our results suggest that estrone modulates EGF receptor by enhancing EGF receptor transcripts and the promoter activity of this gene. PMID- 1753382 TI - Solubilization and sedimentation analysis of muscarinic acetylcholine receptors. AB - To investigate if G-protein-receptor interactions can be characterized using sucrose density gradients (SDG) we have determined the experimental conditions for muscarinic acetylcholine receptor (mAChR) solubilization and analysis on SDG. Solubilization of 65-80% of [3H]QNB bound mAChR was accomplished with 1% of detergent. Analysis of solubilized receptors on SDG containing 0.4 M KCl and 0.1% detergent demonstrated that the physical properties of the receptor-detergent complexes are influenced by the solubilizing detergent as well as detergents included in the SDG. Neither GTP gamma S nor NaF and AlCl3 altered the sedimentation properties of mAChR, suggesting that the solubilized mAChR is no longer associated with G-protein under these conditions. Receptors bound to [3H]oxotremorine and [3H]QNB had similar sedimentation properties, suggesting that, once solubilized, mAChRs do not remain associated with G-proteins. Covalent labeling with [3H]PrBCM followed by solubilization and analysis on SDS-gel electrophoresis demonstrated the presence of intact receptor molecule. These observations suggest that the changes in the sedimentation properties of detergent-receptor complexes are independent of G-protein interactions and are influenced by the nature of the detergent associated with the mAChR during analysis. PMID- 1753383 TI - Effect of age on the kinetics of the binding of iodocyanopindolol to a membrane preparation of rat lungs. AB - The association (k+1) and dissociation (k-1) rate constants, and the equilibrium thermodynamic binding parameters (delta G0, delta H0 and delta S0) of the beta adrenergic ligand [125Iodo]cyanopindolol (ICYP) were studied in a crude lung membrane preparation of rats of different ages. There was no difference in k+1 values for the different age groups, while the k-1-values were in all cases difficult to measure: almost no dissociation of ICYP from its binding site occurs. The thermodynamic properties were not affected by age. It is concluded that, in these experimental conditions, age has no effect on the kinetic parameters of the binding of ICYP to the beta-adrenoceptors in rat lung. PMID- 1753384 TI - The alloantibody response of pregnant women and its suppression by soluble HLA antigens and anti-idiotypic antibodies. AB - The aim of this study was to investigate the time course of maternal allosensitization to fetal HLA antigens during normal human pregnancy and to explore mechanisms of suppression of anti-HLA alloantibodies. We found that the mother produces antibodies against some but not all of the mismatched HLA antigens of the fetus as early as the 8th week of pregnancy. These antibodies (Ab1), however, are often complexed with soluble HLA alloantigens and become detectable when immune complexes are dissociated. Soluble HLA antigens of fetal origin are present in the maternal circulation throughout the entire pregnancy beginning at 8 weeks. In some women the production of anti-anti-HLA antibodies (Ab2) became evident as early as the first trimester, while in others Ab2 was documented during the second or third trimester. Analysis of antibody specificity showed that some healthy primipara develop antibodies reactive with self HLA antigens. Although the allo- and autoantibody responses appear to be modulated by soluble HLA antigens, cyclic variations in the level of alloantibodies, as well as the mother's selective response to some, but not all, paternal HLA antigens, are best explained by the development of anti-idiotypic antibodies. PMID- 1753385 TI - IgG asymmetric molecules with antipaternal activity isolated from sera and placenta of pregnant human. AB - The proportion of symmetric and asymmetric IgG molecules was studied in 10 mothers at delivery. IgG was obtained from peripheral blood and placental blood sera and by elution at 4 M KCl from placenta cell membranes. The percentage of symmetric and asymmetric molecules was determined in the IgG and in their corresponding F(ab')2 fragments by absorption to Con A-Sepharose. The presence of antipaternal antibodies was investigated by IIF and MC tests using paternal lymphocytes. The average percentage of asymetric IgG molecules in the sera was 24.4, which is about double the value of that found in normal subjects. In the IgG eluted from the placenta, the proportion of asymmetric IgG was much higher, averaging 44.4%. Antipaternal antibodies were detected in 5 mothers by IIF and MC and in two mothers only by IIF. In three mothers no antibodies could be detected. It was found that the concentration of antipaternal antibodies was about three times higher in the asymmetric IgG fraction than in the summetric one. Considering the percentage of asymmetric IgG molecules with antipaternal antigen specificity eluted from placenta and the possibility that they function as blocking antibodies, their participation in fetal protection is suggested. PMID- 1753386 TI - Effects of EPF treatment in human mononuclear cells. AB - Early Pregnancy Factor (EPF) is one of the earliest pregnancy associated signals, communicating the ensuing pregnancy to the maternal organism. Data published by others on the mouse suggest that EPF bound to spleen cells causes the release of two H2-restricted "suppressor factors" responsible for the rosette inhibiting activity of EPF in the rosette inhibition test. Using human material, we were able to detect the release of a second entity from mononuclear cells that is able to suppress rosette formation in the human rosette inhibition test. In an attempt to show an intracellular EPF effect in the target cell, cytosolic free calcium concentrations were measured in EPF-treated mononuclear cells from peripheral blood. Our findings did not, however, show any changes of intracellular free Ca(2+)-concentrations under the chosen conditions. PMID- 1753387 TI - Syncytiotrophoblast plasma membrane inhibits membrane expression of activation markers on PHA-stimulated human lymphocytes. AB - Studies have been carried out on the effects of full-term human syncytiotrophoblast plasma membrane (STPM) preparations on the membrane expression of the lymphocyte activation markers HLA-DR, IL-2R, TfR and CD69 during PHA-induced lymphoproliferation. STPM considerably decreases the expression of both late (HLA-DR) and early (IL-2R, TfR, CD69) activation markers at doses which inhibit PHA-induced lymphoproliferation. These results favour the hypothesis that STPM inhibits a very early phase of PHA-induced lymphocyte activation. PMID- 1753388 TI - Hyporesponsiveness to a GnRH vaccine in a non-responder mouse strain is T-cell mediated. AB - Immunization of rats and monkeys with the decapeptide gonadotropin releasing hormone (GnRH) linked to carriers such as diphtheria toxoid (DT) or tetanus toxoid (TT) results in a marked atrophy of the prostate. This vaccine is now being explored for its potential in the "immunosurgery" of prostatic hypertrophy in men and is currently undergoing Phase I/II clinical trials. We have been investigating immunogenetic aspects of immune responses to this hapten-carrier conjugate, and in a recent communication we described the responses of different strains of mice to GnRH conjugated to DT (GnRH-DT). Mice of the 129 (H-2b) strain were found to be non-responders to GnRH. However, further immunization of GnRH-DT immunized 129 mice with GnRH linked to an alternate carrier, TT, resulted in the production of high levels of anti-GnRH antibodies. This showed that 129 mice are not deficient in GnRH-specific B cells and that the lack of response to GnRH in 129 mice is possibly due to (i) the lack of appropriate helper T-cells or (ii) the presence of suppressor cells. In this report we present evidence to support the existence of suppressor cells in GnRH-DT-immunized 129 mice. PMID- 1753389 TI - Reaction of Candida albicans cells of different morphology index with monoclonal antibodies specific for the hyphal form. AB - Two monoclonal antibodies (MAbs), 3D9 with reported specificity for Candida albicans hyphae, and 3B7 with reported specificity for morphological forms of C. albicans found in vivo, were tested by indirect immunofluorescence with C. albicans cells that were grown in 12 different environments (four different culture media incubated at various temperatures) and whose cellular morphology was estimated in terms of morphology index (Mi). Both MAbs reacted strongly with cells with Mi greater than 3.0, i.e., with pseudohyphal and hyphal forms, but in Eagle's medium at 26 degrees C and in a modified Sabouraud's broth medium at 30 degrees C, some reactivity was also found with cells of lower Mi (i.e., yeast forms). Therefore, it was concluded that the hyphal phenotype and the epitopes reactive with the MAbs were co-expressed but that the epitopes could also be expressed independently of the hyphal phenotype. The results confirm the propensity of C. albicans for variation of its surface antigenic composition. PMID- 1753390 TI - Contact-haemolysin production by entero-invasive Escherichia coli and shigellae. AB - Entero-invasive Escherichia coli (EIEC) and shigellae were tested for contact haemolysin (CH) with red blood cells (RBCs) of guinea-pig, rabbit, rat, mouse, monkey, man, sheep and chicken; all bacteria showed the best lysis with guinea pig RBCs. The best culture medium for CH activity of shigellae was tryptic soy broth, and for EIEC it was casamino acid-yeast extract broth with 1 mM CaCl2. CH production by all species was best at the slightly alkaline pH which is optimal for growth; it was also dependent on the presence of a large (140-Mda) plasmid. Pre-treatment of bacteria with homologous antisera inhibited CH activity. Various treatments of bacterial cells and RBCs suggested that CH may be a protein molecule, and that a chitotriose-like moiety may serve as CH receptor. RBCs that were incubated with bacteria at 4 degrees C, or with heat-killed bacteria at 37 degrees C, were not lysed; also, isolated cell-surface components (lipopolysaccharide and outer-membrane protein) did not lyse RBCs. This suggests that metabolically active cells are required for CH activity. Production of CH by both EIEC and shigellae is consistent with a common mechanism for the virulence of these organisms. PMID- 1753391 TI - Surface layers of Eubacterium yurii subsp. yurii and their possible role in test tube brush formation and iron acquisition. AB - Eubacterium yurii subsp. yurii is an anaerobic, gram-positive rod. On isolation E. yurii forms cellular arrangements resembling test-tube brushes (TTB). Although TTB decreased in size and number on repeated laboratory subculture in enriched media, media poor in available iron enhanced formation of these. Plasmids were not demonstrated, even after chloramphenicol enhancement. To characterise the nature and possible physiological roles of the structures of the TTB, they were examined by transmission electronmicroscopy (TEM) with thin-section, negative staining, shadow-casting, freeze-etching and freeze-fracturing techniques, and by scanning electronmicroscopy (SEM). Previous studies by phase-contrast microscopy revealed an amorphous core, the size of which varied in direct proportion to the number of associated bacterial cells. Thin sections of the TTB showed a gram positive cell wall with additional surface layers. Negative staining, shadow casting and freeze etching revealed a surface layer comprising subunits in tetragonal array (P4 symmetry). Shadow casting showed also that the outermost layer of the cells was composed of fibrillar structures closely associated with but distinct from, the tetragonal layer. The fibrils extended from the cell surface in clumps or strands. The presence of these fibrils was confirmed by the freeze-fracture technique and SEM. Chemical analysis of the core material of the TTB showed it to be low in carbohydrate (0.06%) and protein (0.2%). Energy dispersive X-ray spectrometry showed that the core was composed mostly of iron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753392 TI - Histopathological study of porcine gastric mucosa with and without a spiral bacterium ("Gastrospirillum suis"). AB - Tightly spiralled bacteria ("Gastrospirillum suis") were seen in the pyloric mucosa of the stomach of 13 (10.8%) of 120 pigs that appeared clinically healthy at slaughter and in the fundic mucosa of three (5.0%) out of 60 pigs. The spiral organism could not be cultured from any pig. Chronic gastritis was observed in the pyloric mucosa of 53 (44.2%) of 120 pigs and in the fundic mucosa of 7 (11.7%) of 60 pigs. The 13 pigs with spiral bacteria in the pyloric region comprised one animal (7.7%) with normal pyloric mucosa, two (15.4%) with "borderline gastritis", and 10 (76.9%) with chronic gastritis--in one instance accompanied by signs of activity (numerous polymorphonuclear cells). The three pigs with spiral bacteria in the fundic mucosa comprised two animals with a normal fundic region and one with "borderline gastritis". The presence of the spiral bacterium was significantly associated with pyloric gastritis (p = 0.013) and with numbers of lymphoid follicles (p = 0.014). PMID- 1753393 TI - Invasion of HEp-2 cells by strains of Salmonella typhimurium of different virulence in relation to gastroenteritis. AB - Experiments to measure the invasiveness of seven strains of Salmonella typhimurium for HEp-2 cells showed that high inocula (100 bacteria/HEp-2 cell), as used by most workers to synchronise events and to increase the number of bacteria which invade, resulted in recovery of significantly less than 1% of the original inoculum after treatment with gentamicin to kill extracellular bacteria. Also, the cell culture medium became acidic, and microscopic examination of Giemsa-stained monolayers immediately following gentamicin treatment revealed high concentrations of bacteria associated with the cells. Moreover, with bacterium-cell interaction beyond 2 h, many HEp-2 cells became rounded, especially with virulent strains W118 and TML. Thus, the biological significance of the quantitative data was uncertain. The fall in pH and the rounding of HEp-2 cells were prevented by the use of a low (1:1) bacterium: cell ratio; but the recovery of bacteria after treatment with gentamicin was still lower than expected by microscopic examination. After treatment of cells with Triton X-100 to release bacteria, many remained bound to residual cell nuclei. Additional treatment with a rubber policeman, and vigorous pipetting to disperse aggregates of bacteria and cell debris, increased the recovery to c. 10% of the initial inoculum after interaction for 2 h, and 30-80% after 4 h, depending on the strain and experimental conditions. The pattern of invasiveness, but not the absolute count, was highly reproducible on different days and in different hands. However, after interaction exceeding 2 h, the distribution of bacteria was uneven, many cells having no associated organisms, others showing microcolonies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753394 TI - A scheme for the identification of viridans streptococci. AB - A collection of strains representing all the currently recognised species of oral or viridans streptococci (Streptococcus sanguis, S. parasanguis, S. gordonii, S. oralis, S. mitis, S. salivarius, S. vestibularis, S. anginosus, S. constellatus, s. intermedius, S. mutans and S. sobrinus) were tested for the production of a range of glycosidase activities with 4-methylumbelliferyl-linked fluorogenic substrates, and for reactions in a range of conventional fermentation and hydrolytic tests. The resulting biochemical scheme, consisting of 14 tests, enabled the differentiation of all these species and distinguished three biotypes within S. sanguis. The scheme reported here represents an improvement over currently available schemes for the identification of viridans streptococci. PMID- 1753395 TI - Intraosseous administration of lorazepam: same-dose comparison with intravenous administration in the weanling pig. PMID- 1753396 TI - Case report: MRI and CT comparison of an orbital cavernous lymphangioma. PMID- 1753397 TI - The sport of cheerleading. PMID- 1753398 TI - People with AIDS written by a health professional. PMID- 1753399 TI - Opinions on interprofessional relations. PMID- 1753400 TI - New advances in diabetic neuropathy. PMID- 1753401 TI - Ambulatory blood pressure monitoring evaluation of a semi-automated device. AB - The accuracy of a semi-automated ambulatory blood pressure monitoring device (the Instrumedix 'Personal Blood Pressure Transmitter') was assessed in 36 patients undergoing diagnostic cardiac catheterisation. Blood pressure readings measured by the device and by a standard manual sphygmomanometer were compared with simultaneous intra-aortic pressure measured directly via the catheter. No measurement size trends were identified for either of the two comparisons. Compared to direct intra-aortic pressure measurement, the manual sphygmomanometer gave lower systolic (p less than 0.05), and higher diastolic readings (p less than 0.01), while the semi-automated device gave slightly higher readings for both systolic (not significant: p greater than 0.05) and diastolic (p greater than 0.05) pressure. In this assessment the semi-automated device provided at least as accurate a reflection of intra-aortic pressure as did standard manual sphygmomanometry. This device is an accurate tool for the ambulatory assessment of blood pressure where adequacy of treatment or correctness of the diagnosis is in question. PMID- 1753402 TI - A survey of infant and under-5 mortality in Faisalabad Tehsil. AB - A household survey was carried out to study infant and under-5 mortality in urban and rural areas of Faisalabad Tehsil. The overall infant mortality rate was 110.1 (per 1000 live births). The under-5 mortality rate was calculated as 158.6 (per 1000 live births). These rates were higher in rural areas than in urban areas. The infant as well as under-5 mortality rates for females were higher than those for males. PMID- 1753403 TI - Alpha-thalassaemia: prevalence and pattern in northern Pakistan. AB - The level of Hb Bart's is directly related to the inheritance of alpha thalassaemia gene. Hb electrophoresis for Hb Bart's in the cord blood is a very simple method of finding out the prevalence of alpha-thalassaemia gene in a given population. A study was, therefore, carried out to find out the prevalence of alpha-thalassaemia gene in the population of northern Pakistan by estimating the concentration of Hb Bart's in 500 cord blood samples during the period 1986-87 at AFIP Rawalpindi. Hb Bart's was detected in 12 neonates, thus indicating a rate of 2.4% of general population as carrier of alpha-thalassaemia gene. Two distinct groups were recognized. The first group was composed of 9 (75%) neonates, in which Hb Bart's levels varied between 2.0% to 3.5%, while the second group of 3 neonates (25%) showed a level of 5.8% to 6.3%. The former group was considered to be carrying alpha-thalassaemia-2 gene and the latter group as carrier of alpha thalassaemia-1 gene. Neither Hb H disease nor Hb Bart's hydrops foetalis syndrome was detected in this series. PMID- 1753404 TI - Unilateral proptosis in E.N.T. practice. AB - Seventeen cases of unilateral proptosis aged 11-54 years are presented. The proptosis was due to mucormycosis in 7, ethmoid polyposis in 4, malignancy in 4, and one each due to Ringert's tumour and fibrous dysplasia. Surgery was performed in all cases with the aim of total extirpation of disease and orbital repositioning. The surgical approaches included transverse maxillary osteotomy, transantral ethmoidectomy, modified lateral rhinotomy, and orbital decompression. There was one fatality, and two recurrences. Three cases showed satisfactory and eleven excellent results. PMID- 1753405 TI - Dental disorders in Pakistan--a national pathfinder study. AB - A pilot study on dental diseases and treatment needs along with oral hygiene aids used and on provision of dental care was conducted in 1988 using WHO oral health assessment forms. A total of 1146 persons of 12-15 years and 35-65 years were included in the study. The sample was equally distributed in four provinces of Pakistan taking 13 urban and rural areas. Dental caries was found in 55% of children between 12-15 years of age and in 78% of adults. The DMFT index was 1.2 in the younger age group (12 years) and rose to 18.3 for 45-54 years. The percentage of periodontally healthy persons at age 12 was 32% decreasing to 10.4% at age 50. Calculous was the most frequently observed condition in all age groups. PMID- 1753406 TI - Prevalence of HIV-infection among blood donors. AB - Blood donor screening for HIV antibody was carried out at Blood Transfusion Service of Jinnah Postgraduate Medical Centre. Sera of 1655 blood donors were tested by Enzyme linked Immuno-Sorbent Assay (Abbott recombinant HIV-1-EIA) from March, 1987 to December, 1989. Initial reactivity was noted in seven cases, of which three were repeatedly reactive. When these were tested by western blot at National Institute of Health, all were reported negative. Thus no HIV positive blood donor was found in the subject population. PMID- 1753407 TI - Congenital pyloric atresia and epidermolysis bullosa. PMID- 1753408 TI - Lymphomatoid papulosis. PMID- 1753409 TI - Disaster medicine. PMID- 1753410 TI - Nuclear magnetic resonance imaging (MRI). AB - This article discusses the basic concepts of Magnetic Resonance Imaging (MRI) with the intention to introduce the subject to uninitiated. The MRI technique is a powerful noninvasive probe of the body's internal anatomy. In MRI, the images are produced not by X-rays, but through the use of non-ionizing radiowaves that stimulate transitions between spin states of nuclei in a magnetic field when passed through the body. The time required for the nucleus to return to equilibrium gives information about the environment of that nucleus. In this way tissue abnormalities can be determined in vivo. This article covers the basis of MRI phenomena, the concept of magnetic moment of the sample, NMR exalation and emission and the equipment necessary to observe these NMR properties. The primary agents used to increase tissue contrast in MRI are also mentioned. Finally the importance and prospects of this technique in Pakistan have been discussed. PMID- 1753411 TI - Microbiological specimens. PMID- 1753412 TI - In vitro induction of perforin mRNA and cytotoxic activities in human splenocytes by the streptococcal preparation, OK-432. AB - Mononuclear cells were isolated from a spleen excised during surgery and cultured with 0.05 KE (Klinische Einheit)/ml of the streptococcal preparation, OK-432, or 700 JRU (Japan Reference Units)/ml of recombinant interleukin-2 (rIL-2). When the cytotoxicity against K562 and Daudi cells was measured by four-hour 51Cr release assay, OK-432 induced about the same killing activity as that of rIL-2. The peak activity was observed on day 2. When the expression of human perforin messenger RNA (mRNA) was investigated by Northern blot analysis, a low-grade expression was seen in the splenocytes shortly after isolation (day 0). An expression 2.7-fold stronger than that seen on day 0 was produced after one day of culturing with OK 432. This enhanced expression decreased only slightly after the first day. The increases in expression of perforin mRNA on day 2 were similar for OK-432 and rIL 2. The results indicate the multicytokine inducer, OK-432, to induce perforin to about the same degree as rIL-2 does, and perforin to act as one of the effector molecules in the killing activity induced by OK-432. PMID- 1753413 TI - Evaluation of prognostic factors for 233 patients with recurrent advanced breast cancer. AB - We analyzed possible prognostic factors in 233 patients with recurrent advanced breast cancer treated primarily by adriamycin, cyclophosphamide and ftorafur (ACF) therapy and ACF modifications. The patients were in the Cancer Institute Hospital from 1977 to 1986, and were followed-up until 1989. In terms of chemotherapeutic response, complete and partial responses were observed in 31 (13%) and 100 (43%) patients, respectively. The overall median survival from the beginning of chemotherapy was 20.3 months. The factors evaluated were response to chemotherapy, performance status (PS), age, disease-free interval (DFI), menopausal status, number of metastatic sites (step classification), presence or absence of liver metastasis, presence or absence of malignant effusion, and presence or absence of prior radiotherapy. Out of the nine factors, response to chemotherapy, PS, age, DFI and liver metastasis were significant factors affecting survival in univariate analysis, and multivariate analysis of these five factors revealed the survival to be markedly affected by response to chemotherapy (P less than 0.00001), PS (P = 0.00001) and DFI (P less than 0.00001). PMID- 1753414 TI - Tumor thrombus and microvascular invasion as prognostic factors in renal cell carcinoma. AB - The significance of two types of vascular invasion (macroscopic tumor thrombus into the renal vein or vena cava inferior and microvascular invasion) as prognostic factors in renal cell carcinoma is analyzed in 121 patients treated at the Department of Urology, Nara Medical University. The data indicate there to be close correlations between tumor thrombus, microvascular invasion and distant metastasis. In patients with tumor thrombus, however, the prognosis is not as poor when surgical removal of the tumor thrombus is successfully performed as when it is not. In contrast, the prognosis of patients with positive microvascular invasion is significantly worse than that of those with a negative finding. Microvascular invasion appears to be a significant prognostic factor in renal cell carcinoma in addition to well-known factors such as tumor stage, tumor grade, tumor thrombus and distant metastasis. To detect microvascular invasion, the histological examination should be extended to give as much detail as possible. PMID- 1753415 TI - Chemotherapy of soft tissue sarcomas in the extremities. AB - A retrospective study on chemotherapy against soft-tissue sarcomas in the extremities was carried out on 98 patients. The local recurrence rate was 10.3% with intensive chemotherapy in post-1980 patients with high-grade sarcomas but 46.7% without chemotherapy--a fairly significant difference (P less than 0.01). The survival rate was significantly higher with intensive chemotherapy in post 1980 patients with high-grade sarcomas. Thus, intensive chemotherapy based on a new protocol should be given in cases of high-grade sarcoma. Considering surgical margin, the local recurrence rate was 33.3% in post-1980 cases inadequately operated upon but 8.6% in those adequately operated upon, which shows a significant difference (P less than 0.05). PMID- 1753416 TI - Activation of hepatitis B virus infection by chemotherapy containing glucocorticoid in hepatitis B virus carriers with hematologic malignancies. AB - Among 262 inpatients with hematologic diseases who were referred for chemotherapy or immunosuppressive therapy between January, 1985, and December, 1989, nine (3.4%) patients, including two with Hodgkin's disease (HD), three with acute myeloblastic leukemia, one with chronic myelogenous leukemia, two with multiple myeloma and one with aplastic anemia, were found to be hepatitis B virus (HBV) carriers before their chemotherapy began. All six HBV carriers who received chemotherapy containing glucocorticoid showed mild-to-moderate elevations in serum transaminase levels after the chemotherapy. Five showed a rise in titer of the hepatitis B surface antigen, HBsAg. In contrast, three HBV carriers not receiving glucocorticoid showed no change in serum transaminase after chemotherapy. One HBV carrier with HD suffered from severe icteric hepatitis after the withdrawal of multiagent chemotherapy containing glucocorticoid. The HBV-DNA polymerase rose markedly and was accompanied by a marked rise in titer of HBsAg. The results warn us to keep in mind the possibility of glucocorticoid inducing an activation of HBV infection, which may result in severe hepatitis in some HBV carriers. Although further investigation is required, it is recommended that HBsAg-positive patients with hematologic malignancies should, if possible, be treated without glucocorticoid. PMID- 1753417 TI - Spontaneous massive hemorrhage within a malignant tumor of the liver: diagnostic features in sonography and CT. AB - Computed tomography (CT) and sonography performed on four patients with histopathologically proven massive intratumoral hemorrhages in the liver were compared with pathological findings. Unenhanced CT showed a round low-density mass, and enhanced CT produced slight enhancements in the peripheral portions of the masses in two patients which corresponded to histopathologically viable cancerous portions. In contrast, sonography showed multilocular cystic masses with variously shaped septa, assuming a honeycomb appearance. Histopathologically, the septa were made up of blood clots with or without granulation tissue, scar and viable tumor, and the cystic spaces were filled with exudate and erythrocytes. Combined study by CT and sonography could be useful in differentiating massive hemorrhagic malignancies from cystic and necrotic masses and/or simple hemorrhagic lesions. The danger of malignant tumors with massive hemorrhage possibly being diagnosed as benign lesions, such as hematomas and abscesses, is also stressed. PMID- 1753418 TI - Severe herpes simplex virus hepatitis following autologous bone marrow transplantation: successful treatment with high dose intravenous acyclovir. AB - A 17-year-old male patient with T-cell type lymphoblastic lymphoma in complete remission underwent high dose chemotherapy (busulfan 16 mg/kg and cyclophosphamide 120 mg/kg) followed by autologous bone marrow transplantation (ABMT). The patient had been taking oral acyclovir (200 mg x 5) daily from seven days prior to the ABMT (day -7). On day +24, he complained of epigastralgia and general malaise, and the next day his GOT and GPT rose to 570 U/l and 397 U/l, respectively. Although he had no mucocutaneous lesions, hepatitis caused by a herpes virus was suspected, and high dose intravenous acyclovir (10 mg/kg x 3/day) was immediately started. His GOT, GPT and total bilirubin reached peaks of 2,870 U/l on day +26, 1,830 U/l on day +27 and 10.3 mg/dl on day +39, respectively, and rapidly improved thereafter. Serological analyses on IgG antibody titers to herpes simplex virus type 1 using an enzyme-linked immunosorbent assay revealed specific increases (454-fold before transplantation to 3,830-fold on day +46). Antiviral antibody titers to cytomegalovirus, varicella-zoster virus and Epstein-Barr virus showed no significant changes. The serologic markers of hepatitis B virus, hepatitis A virus and hepatitis C virus were all negative. The results indicate the patient's severe icteric hepatitis to have been caused by a reactivation of herpes simplex virus type 1 due to immunosuppression after high dose chemotherapy with ABMT. It is suggested that prompt commencement of high dose intravenous acyclovir is required to treat severe herpes simplex virus hepatitis affecting immunocompromised patients. PMID- 1753419 TI - Local adoptive immunotherapy using lymphokine-activated killer cells and interleukin-2 against malignant pleural mesothelioma: report of two cases. AB - Malignant pleural mesothelioma is refractory to conventional therapy. We tried local adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) to control malignant pleural effusion due to mesothelioma in two patients: Case 1 was that of a 69-year-old man, and Case 2 that of a 49-year old woman with complicating chronic idiopathic thrombocytopenic purpura. A systemic survey revealed no sign of metastasis in either case. Intrapleural instillations of 6.7 x 10(9) autologous LAK cells in Case 1, or 11.3 x 10(9) allogeneic LAK cells in Case 2, with daily injections of IL-2 resulted in reductions of the pleural effusions in each case and in a decline in the level of hyaluronic acid in the effusion, in Case 1. The instillations of autologous and allogeneic LAK cells were well tolerated. The results suggest that local adoptive immunotherapy could be useful in the treatment of malignant effusion due to mesothelioma. PMID- 1753420 TI - Pure red cell aplasia associated with non-Hodgkin's lymphoma and hemolytic anemia. AB - Pure red cell aplasia (PRCA) rarely occurs in non-thymic lymphoproliferative disorders. The present article describes a patient with non-Hodgkin's lymphoma (follicular, mixed type), who concurrently developed PRCA and warm type autoimmune hemolytic anemia during the clinical course. The PRCA and hemolytic anemia were successfully treated with prednisolone (60 mg/day). The patient died two years later, however, from advanced lymphoma without any recurrence of the PRCA or hemolytic anemia. To our knowledge, only 20 cases of PRCA associated with malignant lymphoma have been reported. The pathogeneses of the PRCA and hemolytic anemia in our patient are discussed. PMID- 1753421 TI - [Relationship between morphological and functional changes in the stomach with aging]. AB - The authors investigated the relationship between morphological changes and functional changes of the stomach with ageing, especially in term of change of gastric emptying in 92 healthy subjects. We checked the difference in chronological age and the stomach age in these subjects (in order to assess these subjects). The morphological change was evaluated by extent of atrophic gastritis in endoscopical atrophic border and histological findings of biopsy specimens, and the functional change was evaluated by maximal acid output in gastric secretion. Atrophic gastritis was expanded and maximal acid output was significantly reduced with ageing. From these results we confirmed that there was no difference between the chronological age and the stomach age and the quality of these subjects was very good. Gastric emptying was investigated by the acetaminophen method. In spite of ageing, gastric emptying was almost constant in these healthy subjects. PMID- 1753422 TI - [Long-term single dose chemoprophylaxis of recurrent urinary tract infection in elderly female subjects]. AB - To evaluate the efficacy of the single dose chemoprophylaxis of recurrent urinary tract infection (UTI) in the elderly, 20 female inpatients (mean age 81.4) who had one or more culture documented UTIs in the past 12 months were studied. They were randomly assigned to be treated for 6 months either with chemoprophylaxis (200 mg of norfloxacin) or conventional therapy (without any antimicrobials except when overt UTI occurred). After a 4 months of washout period, the protocols were exchanged with each other and next 6 months of trial was carried out. All cases were followed at least 4 months after the discontinuance of the chemoprophylaxis. The difference of efficacy between the two modalities was evaluated by periodical examinations of urine cultures, urinalysis and inflammatory markers. During chemo-prophylaxis, the frequency of the symptomatic UTI (bacteriuria greater than 10(4)/ml, pyuria greater than 5/HPF, CRP greater than +) was 0.267/patient.year which was significantly lower than during conventional therapy (2.97/patient.year, p less than 0.01). This prophylactic effect remained 4 months after the discontinuance of the drug. On the other hand, bacteriuria was persistent in more than half of patients with chemoprophylaxis. Minimal inhibitory concentration of norfloxacin for separated bacteria revealed that the resistant species steeply increased from 4 to 6 months after the beginning of chemoprophylaxia. These species disappeared 4 months after the drug was discontinued. Optimal durations of chemoprophylaxis and drug-holidays were discussed. PMID- 1753423 TI - [Echocardiographic assessment of the effect of aging on the diastolic and systolic functions of the left ventricle]. AB - The effects of aging on the diastolic and systolic functions of the left ventricle were studied by echocardiography as follows. (1). Maximum velocity of circumferential fiber lengthening (negative peak Vcf) and shortening (peak Vcf) was assessed by digital M-mode echocardiography in 20 healthy young subjects and 26 healthy elderly subjects. The mean value of negative peak Vcf (-cir/sec) was 3.87 +/- 0.85 in the 20's. -4.48 +/- 1.14 in the 30's, -3.71 +/- 1.21 in the 40's, -2.70 +/- 0.90 in the 60's, -2.57 +/- 0.64 in the 70's, -2.33 +/- 0.77 in the 80's and -2.57 +/- 0.65 in the 90's showing significant difference among young and elderly groups (p less than 0.05- p less than 0.005). The mean value of peak Vcf showed no significant difference among young and elderly groups except for the group in the 30's which showed significant (p less than 0.05) difference between other groups. (2). Indices of the left ventricular systolic and diastolic functions were calculated by standard M-mode echocardiographic technique in 227 healthy subjects from 5 to 94 years in age by dividing them into 3 young groups and 4 elderly groups. As for the left ventricular internal diameters a tendency of increase was observed in the end diastolic diameter of the left ventricle in accordance with ageing. Fractional shortening of the left ventricular diameter which ranged from 36.2% to 36.7% in the 3 young groups and 36.9 to 40.3% in the 4 elderly groups and cardiac output showed no age dependent decrease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753424 TI - [Decreased cerebral blood flow in remote areas in deep-seated cerebrovascular lesions]. AB - Recent positron or single photon emission computed tomographic studies have demonstrated that the impairment of regional hemodynamics or metabolism in cerebrovascular disease is not limited to the focal lesion, but also involves more remote areas. The present study evaluated cerebral blood flow in areas remote from the primary lesion in patients with subcortical cerebrovascular disease, and assessed correlations with the clinical features. Twenty patients aged 61-89 (mean, 74.7 +/- 6.7 years) were divided into the L group (lacunar infarction in deep penetrating arterial territory, n = 7), the NL group (non lacunar subcortical infarction caused by main trunk occlusion or severe stenosis, n = 6), and the H group (putaminal or thalamic hemorrhage, n = 7). Ipsilateral cortical and contralateral cerebellar blood flow were assessed using single photon emission computed tomography with 123I-IMP. Although only some patients of the L group showed a mild reduction of ipsilateral cortical blood flow, most of the patients in the NL and H groups showed a moderate or severe flow reduction. The cortical blood flow reduction was suggested to be caused by several mechanisms, including brain edema, a decreased perfusion pressure associated with disease of large arteries, partial cortical neuronal damage, and deactivation. The degree of the flow reduction was considered to depend on the relative contribution of each of these factors. Contralateral cerebellar blood flow reduction, i.e., crossed cerebellar diaschisis, was observed more frequently and prominently in the NL and H groups than in the L group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753425 TI - [Efficacy and safety of percutaneous endoscopic gastrostomy in the elderly]. AB - Percutaneous endoscopic gastrostomy (PEG) was performed in 32 patients with nasogastric feeding (NGF) or total parenteral nutrition (TPN), who were unable to swallow. Our cases of PEG included 10 with dementia, 8 with cerebral infarction, 8 with cerebral bleeding, 3 with gastric cancer, and others. TPN was performed after PEG for a short time. Because of the combination of TPN and PEG, there was no mortality or major complication related to the procedure. Minor complications included subcutaneous abscess and TPN catheter fever. PEG can be safely and rapidly performed. Furthermore, painless life, better cosmetic features and physical condition can be obtained with this procedure. The majority of the patients are able to return home after PEG. PEG can improve the quality of life of the patients who cannot swallow but have an intact gut. PMID- 1753426 TI - [The coefficient of variation of RR intervals (CVRR) on electrocardiogram in patients with essential hypertension with reference to aging, hemodynamics and sympatho-adrenomedullary function]. AB - To evaluate the significance of parasympathetic nerve activity in essential hypertension, we measured the coefficients of variation of RR intervals (CVRR) on electrocardiogram and examined the relationships between CVRR and aging, hemodynamics and sympatho-adrenomedullary function in normotensive subjects (NT) and in patients with essential hypertension (EHT). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA), plasma adrenaline concentration (pAd) and CVRR resting in a supine position were simultaneously measured in 37 NT (33.8 +/- 2.0 years) and 47 mild-to-moderate EHT (51.3 +/- 1.5 years). In both NT and EHT, significantly negative correlations between CVRR and age (NT: r = -0.54, p less than 0.001, EHT: r = -0.41, p less than 0.005) were observed, however, CVRR correlated with neither MAP, HR nor pAd. CVRR tended to correlate negatively with pNA (r = -0.27, p less than 0.1) in NT, unlike in EHT. The mean value of CVRR in EHT (n = 10, age: 38.3 +/- 1.6 years, CVRR: 3.61 +/- 0.37%) was significantly (p less than 0.005) lower than in age-matched NT (n = 10, age: 38.3 +/- 2.5 years, CVRR: 5.76 +/- 0.45%). These results indicate that the parasympathetic tone suggested by CVRR may be related to aging and sympathetic nerve activity, and that parasympathetic function might be impaired in EHT. PMID- 1753427 TI - [Diurnal changes in postheparin lipolytic activity (PHLA) and the role of PHLA in triglyceride catabolism in young and middle-aged obese individuals]. AB - The diurnal changes in postheparin lipolytic activity (PHLA) were studied as on aspect of its physiological changes in eight healthy volunteers in a fasting state. Serum lipids and PHLA in obese males were measured to determine the etiology of obesity-associated hypertriglyceridemia with respect to triglyceride (TG) catabolism. In the healthy nonobese volunteers, the lipoprotein lipase (LPL) activity did not show any diurnal changes, but decreased with time during fasting. The hepatic triglyceride lipase (HTGL) activity underwent diurnal changes, and was high in the morning and low at night. Perceiving the metabolic difference between young obese individuals (obese since childhood) and middle aged obese individuals (obese since adulthood), PHLA and serum lipids were simultaneously determined and examined from the aspect of TG catabolism in a young male group aged 17-27 and an older male group aged 35-62. The lower-age group consisted of 15 normal-weight men and 25 obese men with 11 years (mean) of a history of obesity. The higher-age group consisted of 15 normal-weight men and 25 obese men with 12 years of a history of obesity. No differences were found in total cholesterol and LDL-cholesterol between the normal-weight and obese individuals of both groups. However, HDL-cholesterol was significantly decreased, only in the obese individuals of the higher age group, compared to the normal weight individuals of this group. Serum TG and insulin were significantly higher in the obese individuals than normal-weight individuals of both groups. In the obese individuals in both groups, a positive correlation was demonstrated between serum TG and insulin. This suggested the increased production of TG in association with hypertriglyceridemia. In addition, TG positively correlated with LPL and HTGL activities in young obese individuals, while a negative correlation was demonstrated only between TG and LPL activity in older obese individuals. These results indicated an age-related difference in TG catabolism in obese individuals with obesity-associated hypertriglyceridemia. PMID- 1753428 TI - [MRI and ultrasonography of atherosclerosis of the thoracic aorta and carotid arteries in elderly hypercholesterolemic patients]. AB - In 53 elderly participants aged more than 60 the thoracic aorta and bilateral carotid arteries were observed with noninvasive techniques, MRI and ultra sonography, in order to elucidate the relationship between hypercholesterolemia and atherosclerosis in the elderly. Hypercholesterolemic subjects were classified as group H (serum total cholesterol (TC) greater than 220 mg/dl), group H-I (220 mg/dl less than TC less than 250 mg/dl) and group H-II (TC greater than or equal to 250 mg/dl). Atherosclerotic changes of the thoracic aorta were observed in 46% of group H, 27% of group H-I, 60% of group H-II and 37% of normolipidemic subjects (group NL). Carotid atherosclerotic changes were observed in 19% of group H, 9% of group H-I, 27% of group H-II and 18% of group NL. In group H-I, the percentages of atherosclerotic changes in both thoracic aorta and carotid arteries were lower than those in group NL. However, atherosclerotic changes of thoracic aorta and carotid arteries were detected in 43% and 29% of the subjects showing higher apo B/Apo Al ratio than 1.0 among group H-I + NL (TC less than 250 mg/dl). These changes occurred in 32% and 13% of the subjects showing lower apo B/Apo Al ratio than 1.0 among the same groups. Namely, atherosclerotic changes of the thoracic aorta and carotid arteries were observed more frequently in the subjects showing a higher apo B/Apo Al ratio than 1.0 even if their serum cholesterol values were not higher than 250 mg/dl. We should use not only the serum cholesterol value but also the apo B/Apo Al ratio as an indicator to evaluate the roles of lipids in the development of atherosclerosis. PMID- 1753429 TI - [The correlation between pulse wave velocity and diabetic angiopathy]. AB - Pulse wave velocity (PWV) of the aorta was measured in 40 patients with diabetes mellitus, in order to study the relation between PWV and diabetic angiopathy. The PWV was significantly faster in diabetic patients on oral hypoglycemic agents than in those on diet alone or on insulin. The PWV correlated significantly and positively with age, systolic blood pressure and urinary albumin index. The PWV significantly faster in diabetics with microalbuminuria than in those without this findings. It was concluded that PWV in addition to known risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and elevated blood glucose, may be a reliable index of diabetic micro- and macroangiopathy. PMID- 1753430 TI - [Serum uric acid and factor VII hyperactivity in the elderly]. AB - To study the relationship between serum uric acid, lipid fractions, and coagulation factor VII (FVII) in the elderly, we measured FVII coagulation activity (FVIIc). FVII antigen (FVIIag), in 138 normal subjects without alcohol intake ranging in age from 60 to 98 years. We also measured blood lipid fractions including apolipoprotein A-I, A-II, B, E, and serum cholinesterase activity (ChE). Serum uric acid levels significantly correlated with FVIIc (p less than 0.01) and FVIIag levels (p less than 0.05) as well as with tryglycerides, VLDL, LDL, total cholesterol, and ChE in elderly men, but not in women. However, multiple regression analysis showed these correlations in elderly men were not significant, after excluding the effect of triglycerides and VLDL. These results also suggest that elevation of uric acid may be a coronary risk factor in elderly men through high FVII levels. PMID- 1753431 TI - [Statistical analysis of post-stroke patients in a rehabilitation institution]. AB - A retrospective analysis of 312 stroke patients (200 men, 112 women; average age 65) admitted to Yamaguchi Rehabilitation Hospital during the past three years showed the following results. 1) After an average period of stay of 244 days 225 patients were discharged to home, general hospitals, extended care facilities, or nursing homes. 2) The group of patients over 80 years of age at admission had a lower ratio of home returns than in other groups (p less than 0.01). 3) Patients who returned home had higher scores not only on discharge Barthel index scores but on admission Barthel index scores, compared with other discharged patients (p less than 0.01). 4) The higher the admission Barthel index score, the shorter the period of stay (p less than 0.01). Concerning discharge Barthel index scores, patients who stayed over two years had lower scores than patients who stayed less than two years (p less than 0.01). The results of this analysis suggest the importance of determining goals and programs taking admission Barthel index scores as well as other available factors into consideration for patients with stroke admitted to rehabilitation institutions. PMID- 1753432 TI - [Gastric xanthomas in the elderly]. AB - Gastric xanthomas are single or multiple yellowish-white small nodules or plaques in the gastric mucosa. Microscopically they consist of macrophage-derived foam cells full of lipids. However, because of their benign nature, there are few reports of gastric xanthomas in the literature and their clinical significance still remains unknown. In this study, we studied 131 elderly cases (42 males and 89 females) with the average age of 75.6 +/- 12.3 (S.D.) years old who were examined gastroendoscopically. The endoscopic finding of gastric xanthomas was observed in 17 males (40.5%) and in 23 females (25.8%). Gastric xanthomas tended to increase with age, and the frequency was highest in the seventies (40.0%). Of the xanthoma cases, 42.5% had a solitary xanthoma, and 17.5% had more than 5 xanthomas. More than 70% of xanthomas were observed in antral and pyloric regions. There was no difference in serum lipids between the cases with and without xanthomas. Gastric mucosa biopsied from around xanthomas showed moderate to severe atrophic change of gastric glands in most cases (89%). Hyperplasia of gastric-pit epithelia and intestinal metaplasia were also often observed. However, there was no correlation between gastric xanthomas and small round cell infiltration in the gastric mucosa. It was concluded that gastric xanthomas in the elderly arise from the mucosa with atrophic change in most cases, which may have a disturbance of local lipid metabolism, and that the presence of gastric xanthomas may be a marker of the pathological aging change of gastric mucosa. PMID- 1753433 TI - [A case of psoas abscess due to renal pelvic carcinoma complicated with non ketotic hyperosmolar diabetic coma]. AB - A 85-year-old man was admitted to our hospital because of semicomatous status. Laboratory data on admission showed elevation of blood sugar (823 mg/dl) and serum osmotic pressure (345 mOsm/l), but ketonuria was not detected. Non-ketotic hyperosmolar diabetic coma was diagnosed. The insulin infusion and physiological saline improved the blood sugar level and consciousness within a day. The abdominal ultrasound examination revealed an abscess in the left kidney and right psoas muscle. The same findings were seen by abdominal computed tomography but the possibility of malignant neoplasm of the left kidney could not be ruled out because of a swelling of the left adrenal gland. Pain associated with psoas abscess and low grade fever were observed. Because of his poor general condition, drainage of the abscess was not performed and conservative therapy using antibiotics was administered. Without any improvement of the abscess, he died due to general deterioration four months later. Autopsy findings showed carcinoma of the left renal pelvis and metastasis to the right psoas muscle, left adrenal gland, liver, bilateral lungs and lymph modes. Psoas abscess is a relatively uncommon disease, especially in elderly patients. The etiology of the disease is divided into primary and secondary causes. Most secondary psoas abscess cases are caused by intestinal diseases, and Crohn's disease has been related to the highest incidence. A few cases of psoas abscess caused by colorectal carcinoma have been reported. Ultrasound and computed tomography are useful in diagnosing this disease and drainage of an abscess is necessary for therapy and proving the cause. Cancer metastasis should considered in differential diagnoses, when psoas abscess is seen in elderly patients. PMID- 1753434 TI - [Cerebral infarction and high serum levels of muscle-derived enzymes associated with abrupt increase in hematocrit in a patient with secondary erythrocytosis]. AB - A 70-year-old man was admitted to our hospital because of fever and progressive dyspnea in December 1989. He was already diagnosed as having erythrocytosis secondary to pulmonary fibrosis 4 years previously and the values of his hematocrit (Ht) were maintained between 44.5 and 62.9% by repeated phlebotomy. Immediately after admission, severe diarrhea developed and the Ht value was 61.5%. Around 1:30 a.m. of the 3rd hospital day, he developed disturbance of consciousness. In addition, the serum levels of LDH, CPK, aldolase, and myoglobin of muscle origin increased markedly and the Ht value showed 78.5%. While the level of consciousness was gradually restored by 600 ml phlebotomy and 1,500 ml saline infusion, dysarthria and hemiplegia became evident. The Ht value early in the morning of the 3rd hospital day was reduced to 59.4%. Although cranial CT and MRI performed 74 days and 15 months, respectively, after the onset of the symptoms failed to reveal any abnormal shadow, he was clinically suspected to have cerebral infarction. These findings emphasize that abrupt increase in Ht or blood viscosity is a possible factor triggering cerebral infarction, and adequate control of Ht value is recommended for the prevention of such a condition in the aged. PMID- 1753435 TI - [A senile patient with Rendu-Osler-Weber disease who underwent resection of 4 multiple bilateral pulmonary arteriovenous fistulas]. AB - A 70-year-old female patient with multiple bilateral pulmonary arteriovenous fistulas was referred to our hospital for its treatment. She had experienced frequent epistaxis and had nasopharyngeal telangiectasia. Her mother, sister and all four children also suffered from epistaxis. We diagnosed this patient as Rendu-Osler-Weber disease combined with multiple bilateral pulmonary arteriovenous fistulas. Her chest roentgenogram revealed 4 arteriovenous fistulas in the left lung and 2 arteriovenous fistulas in the right. On admission arterial blood gas analysis while breathing room air showed a PaO2 of 39.8 torr and an SaO2 of 75.4%. The percent of R-L shunt was calculated to be 56.5%. Because of severe hypoxemia, she underwent resection of four large fistulas in segments 3, 4, 5, and 8 of the left lung. Twenty-eight days after the operation, the PaO2 was 76.4 torr and SaO2 was 95.7%. There was no sign of enlargement in size of the remaining arteriovenous fistulas. PMID- 1753436 TI - Single DNA marker generated by "YAC-Alu PCR" that is end-specific. AB - A simple strategy for the rapid preparation of an end-specific linking-DNA probe from the YAC-human chromosome 21 DNA recombinant clone and the characterization of this single DNA probe are described. Synthetic oligodeoxynucleotide primers, based on the consensus Alu sequence, and the Sup4 DNA fragment in the YAC arms were used to amplify end-specific DNA sequences by the polymerase chain reaction (PCR) for screening of the linking YAC recombinant clones ("YAC-Alu PCR"). Nucleotide sequencing of the product of PCR from human genomic DNA in a YAC insert confirmed the boundary between the vector and the insert and the presence of the 3'-end Alu-like structure. The probe R1, prepared by "YAC-Alu PCR" amplification, was assigned to chromosome 21 by Southern hybridization of somatic cell hybrid DNAs. In situ hybridization allowed localization of the R1 DNA probe to the human chromosome 21q21-q22.1 region. Thus, this approach has significant advantages not only for isolation of a single DNA probe specific for human chromosome 21 but also for the screening of YAC linking recombinant clones for mapping of the human genome. PMID- 1753437 TI - A 3' splice site consensus sequence mutation in the intron 3 of the alpha galactosidase A gene in a patient with Fabry disease. AB - Fabry disease is an X-linked disorder accompanied with accumulation of glycosphingolipids resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-GalA). In the present study, mRNA for alpha-GalA in fibroblasts from an 11-year-old Japanese patient with Fabry disease was examined using the reverse transcriptase-polymerase chain reaction (PCR). The shorter message of alpha-GalA was demonstrated in this patient when compared with the normal control. The complete deletion of exon 4 in the mRNA for alpha-GalA in the patient was disclosed by analysis of cDNA with restriction enzyme digestion and asymmetrical PCR sequencing. The direct sequencing of the genomic DNA demonstrated a single base substitution (G----A) at the 3' end of the consensus sequence of intron 3. This mutation destroyed a splice site in the alpha-GalA, which produced a mutant allele. It was also shown that the mother of the patient had this mutant as well as normal alleles as a heterozygote. PMID- 1753438 TI - Unilateral gonadal dysgenesis with both testis and fallopian tube on the same side in a 45,X/46,X inv (Y) mosaic male. AB - A 5-year-old male with ambiguous external genitalia, hypospadias and microphallus without an urethral orifice was referred for cytogenetic studies. Exploratory laparotomy revealed presence of an infantile uterus and unilateral gonadal dysgenesis with both testes and fallopian tube on the right side. The metaphase cells from peripheral blood culture showed both 45,X/46,X inverted Y (p11.2q11.23) cell-lines (98:2). The inverted Y was found to be of paternal origin. Maternal chromosomal pattern was normal 46,XX. The presence of a fallopian tube next to testis suggest absence of secretion of anti-Mullerian hormone by Sertoli cells. The absence of Wolffian duct derivatives suggest insufficient secretion of testosterone by Leydig cells. PMID- 1753439 TI - Partial 18q trisomy and 18p monosomy resulting from a maternal pericentric inversion, inv(18)(p11.2q21.3). AB - A 7-year-old boy with dysmorphic features was found to have a recombinant chromosome 18, rec(18), resulting from meiotic recombination of a maternal pericentric inversion, inv(18) (p11.2q21.3), as defined by high-resolution banding. He was trisomic for the long arm (q21.3-qter) and monosomic for the short arm (p11.2-pter) of chromosome 18. His clinical features were compared with those in other rec(18) cases, and also those in monosomy 18p, trisomy 18qter and full trisomy 18 syndromes. The risk of recombinant formation for inv(18) carriers was also discussed. PMID- 1753440 TI - Chromosomal and biochemical screening on mentally retarded school children in Taiwan. AB - Governmental officials as well as medical scientists in Taiwan have worked hard in recent years to develop and to implement various measures, such as prenatal diagnosis and neonatal screening, to lower the incidence of hereditary diseases and mental retardation in the population. An inquiry into the possibility of devising a chromosomal and biochemical screening program and to apply it routinely to all the mentally retarded school children island-wide was the major aim of the present study. A collection of 1,614 blood samples was screened for phenylketonuria (PKU), galactosemia, homocystinuria, biotinidase deficiency, and congenital hypothyroidism. The IQ of these children ranged from 50-75 (1,397 children, moderate group) to less than 50 (217 children, severe group). Six cases of PKU (one tetrahydrobiopterin deficient and five classical) and three cases of thyroid dysfunction were found. The overall incidence of these two diseases was 0.56%. Of the 1,614 blood samples, 1,323 were cultured and karyotyped successfully. One hundred and twenty-five of them had chromosome abnormalities. The majority (64 out of 125) were trisomy 21. A remarkable difference in the percentage of mentally retarded children with chromosome abnormalities was observed between the moderate (7.87%) and severe (17.51%) retarded. PMID- 1753441 TI - The prevalence at birth of cogenital malformations at a maternity hospital in Osaka City, 1948-1990. AB - The frequencies of congenital malformations at St. Barnabas' Hospital, Osaka were studied during the period 1948-1990. There were 1,418 malformed infants diagnosed during the first week of life among a total number of 131,996 births during the period. Of the 1.07% of malformed children, 0.90% had single and 0.17% had multiple malformations. The birth prevalence was 1.07% in singletons and 1.20% in twins. There was significant difference in prevalence between males (1.15%) and females (0.97%). The prevalence was 0.88% for the period 1948-1958 and increased with each year cohort up to the recent period when the value was 1.38%. Varus deformities of feet was the most common defect (23.4 per 10,000 births), followed by polydactyly (finger) (7.8), anencephaly (7.1), cleft lip and palate (6.5), syndactyly (toe) (6.5), cleft lip (6.3), and Down's syndrome (6.1). The prevalence of conjoined twins was 1 in 65,551 deliveries. Significant differences occurred between males and females for cleft palate, cleft lip and palate, syndactyly (finger), oligodactyly (finger), and hypoplastic auricle. The prevalences for valgus deformities of feet, syndactyly (toe) and atresia ani increased significantly with the year cohort, whereas the prevalence of cleft palate decreased significantly with the year cohort. Overall prevalence was significantly higher in 1970-1990 (1.28% than in 1948-1969 (0.88%). Similar results were examined for cleft lip and palate, syndactyly (finger), syndactyly (toe), hypospadias, hydrocele testis, and Down's syndrome. PMID- 1753442 TI - [Electromagnetic fields: their biological effects and regulation]. AB - Concern over the effects of humans of ELF-(extremely low frequency; less than 300 Hz) electromagnetic fields has rapidly increased in recent years. The effects seem to be related to gene level aberrations such as carcinogenesis and developmental malformations, but it is difficult to obtain experimental evidences on field effects. Several safety guidelines or permissible doses have been proposed for electromagnetic wave, but they mainly cover the range of microwave frequencies. Three of the guidelines made in 1989-1990 included ELF electromagnetic fields and two newly approved guidelines on power-frequency electromagnetic fields appeared in 1990. However, they adopted considerably different values based on different theoretical standpoints. Generally, the concept of electromagnetic fields appears to be confused with that of magnetic field and thus the ideas for protective measures conflict between the two. The author first presented the concepts of electromagnetic and magnetic fields, then briefly discussed their biological effects together with the underlying mechanism, and lastly described these drafts on safety standards or permissible doses. Since subtle and difficult problems remain to be resolved, further investigation will be required in order to put these guidelines into practice. PMID- 1753443 TI - [Industrial hygienic study on nursing activities. I. Investigation on heart rate and energy expenditure of ward nurses by nursing activity]. AB - Using a Holter electrocardiograph (ECG), we recorded the heart rates of ward nurses by working hours and nursing activity. Energy expenditure was calculated from the heart rate data and nurse work lord was evaluated. The following results were obtained. 1) Average heart rates were 77 (beats/min) for day-shift nurse in surgical ward, 76 for evening-shift nurse in mixed, ward, and 74 for night-shift nurse in mixed ward. 2) The energy expenditures per day were calculated to be 3,474 kcal for day-shift nurse in surgical ward, 3,060 kcal for evening-shift nurse in mixed ward, and 3,238 kcal for night-shift nurse in mixed ward. 3) The energy expenditures during working hours were 2,110 kcal/510 min for day-shift nurse in surgical ward, 1,805 kcal/495 min for evening shift nurse, and 2,014 kcal/570 min for night-shift nurse in mixed ward. 4) The highest energy expenditures of nurse engaged in direct nursing care were 834 kcal (39.5%) for day-shift nurse in surgical ward, 632 kcal (34.9%) for evening-shift nurse in mixed ward, and 790 kcal (39.2%) for night-shift nurse in mixed ward. 5) The longest working hours were 174 min (34.1%) in assisting with medical examinations and treatment by day-shift nurse, 155 min (31.3%) in direct care by evening-shift nurse, and 222 min (39.0%) by night-shift nurse. The results indicate that the energy expenditure calculated from the average heart rate of ward nurses in higher than that of other types of workers. The reason for this difference is discussed in this report. Also, this study showed that the energy expenditure determined by this method does not necessarily increase in proportion to working hours. PMID- 1753444 TI - [Multivariate analysis on subjective symptoms in forestry workers using chain saw]. AB - This study was conducted to evaluate the relationship between the prevalence of subjective symptoms in workers using vibrating tools and the duration of chain saw operation and to examine whether the symptoms were relevant to factors other than the usage of vibrating tools. The statistical model of multivariate analysis was adapted to analyze individual data on the subjective symptoms of 317 chain saw operators. The obtained results were as follows: 1. In analysis of covariance, age-adjusted operating year in workers with peripheral circulatory, peripheral neurological and musculoskeletal disturbances was significantly longer than that without such disturbances. For these disturbances, partial regression coefficients of operating year were significantly high in multiple regression analysis. These results show that these disturbances and age-adjusted operating year are mutually closely related. 2. Multiple regression analysis showed that the partial regression coefficients of both operating year and age were low for nine symptoms, i.e. dulling sense of touch, joint pain, headache, dizziness and/or tinnitus, profuse sweating, discomfort of stomach, palpitation and/or dyspnea, hearing disturbance and lumbago. These results suggest that such symptoms were not related to either age or chain saw operation. 3. The results of principal component analysis were visualized in three-dimensional space in order to evaluate the relationships among the symptoms. The analysis showed that peripheral circulatory and neurological disturbances appeared independently and that general symptoms such as easy fatigability, headache, forgetfulness, vertigo and/or tinnitus, easy irritability, sleep disorder, profuse sweating, discomfort of stomach, palpitation and/or dyspnea, shoulder stiffness, hearing disturbance and lumbago consisted of four independent groups. Each group has no relationship with duration of chain saw operation. This suggests other harmful factors of the groups play a role in the prevalence of the symptoms. PMID- 1753445 TI - [The evaluation of serum creatine phosphokinase for estimation of energy expenditure in human subjects]. AB - We investigated the relationship between serum creatine phosphokinase (CPK) activity and energy expenditure in young adults and evaluated whether serum CPK activity is a useful index of energy expenditure. These data were obtained from 225 (men: 94, women: 131) healthy young adults. The results of the survey were as follows: In men, there was a statistically significant correlation between serum CPK activity and energy expenditure (r = 0.370; p less than 0.01; y = 1986.0 + 8.2x), energy expenditure/body weight (r = 0.270; p less than 0.01 y = 35.4 + 0.06x) and daily activity index (r = 0.357; p less than 0.01; y = 0.38 + 0.0030x) In women, there was a statistically significant correlation between serum CPK activity and energy expenditure (r = 0.207; p less than 0.05; y = 1895.0 + 3.0x), and daily activity index (r = 0.194; p less than 0.05; y = 0.432 + 0.0017x). The higher the proportion of exercising subjects, the higher was the serum CPK activity. These results suggest that measurement of serum CPK activity can be used to evaluate energy expenditure. PMID- 1753446 TI - [Evaluation of sensory disturbances using short-latency somatosensory evoked potentials (SSEPs) in vibration-exposed workers]. PMID- 1753447 TI - [Significance of blood pressure at the time of work place health checkup in comparison with 24-hour ambulatory blood pressure]. PMID- 1753448 TI - [DNA-adduct detection in rats administered with 4,4'-methylenedianiline or 4,4' methylenebis (2-chloroaniline)]. PMID- 1753449 TI - Down regulation of serotonin uptake sites in rat brain induced by concomitant chronic administration of desipramine and repeated stress. PMID- 1753450 TI - Effects of hippocampal neurotoxicant, trimethyltin, on corticosterone response to a swim stress and glucocorticoid binding capacity in the hippocampus in rats. PMID- 1753451 TI - Plasma beta-phenylethylamine levels in mood disorders. PMID- 1753452 TI - The tail suspension test for screening antidepressant drugs: comparison of movement in ICR and NMRI mice. PMID- 1753453 TI - Characterization of human platelet [125I]R-DOI binding sites by in vitro autoradiography. PMID- 1753454 TI - Modulation of 5-HT2 receptor-mediated intracellular calcium movement in platelets and its function in affective disorders. PMID- 1753455 TI - Rat hippocampal 5-HT1c receptor binding and 5-HT1c receptor mediated rat blood corticosterone responses. PMID- 1753456 TI - Effects of Ca2+ antagonists on NA-induced intracellular Ca2+ mobilization in rat cultured neurons. PMID- 1753457 TI - Effects of repeated treatment with electro-convulsive shock and imipramine on serotonin2 receptor functions. PMID- 1753458 TI - A clinical study on intellectual impairment in parkinsonian patients during long term treatment. AB - The severity of intellectual impairment of 89 patients with Parkinson's disease was evaluated with the Osaka Intelligence Scale for the Aged (OISA). Based on their intelligence levels, the patients were divided into three groups: normal, slight dementia and dementia. EEGs, psychiatric complications such as hallucination, degree of motor disability, history of medication, relationship between changes in intelligence and total amount of administered drugs were also examined. There was no significant correlation between the length of duration of the illness and the degree of intellectual impairment. Two characteristic subgroups were found among our subjects: a group of patients who rapidly became demented after the onset of Parkinsonism, and a group of patients whose intelligence was preserved for a longer period. The mean age of the onset of the disease in the former group was older than that of the latter. Patients of the former group exhibited psychiatric complications and EEG abnormalities more frequently. The severity of motor disability and medications administered at the time of the OISA examination did not differ between the two groups. Deterioration of the intelligence of the patients with Parkinson's disease did not correlate with the total amount of the administered antiparkinsonian drugs. PMID- 1753459 TI - Biochemical characteristics of the membrane-inserted protein kinase C in the rat brain membrane. PMID- 1753460 TI - Effect of chronic administration of trazodone on the 5-HT 1A mediated inhibition of forskolin-stimulated adenylate cyclase activity. PMID- 1753461 TI - The functional maturation of fetal biological rhythm. PMID- 1753462 TI - Alteration of circadian rhythm in shift-working ambulance personnel. PMID- 1753463 TI - Pattern, trough and amplitude of rectal temperature during sleep in healthy subjects. PMID- 1753464 TI - Effects of clothing types on the circadian rhythm of human core temperature. PMID- 1753465 TI - Menstrual cycle and vaginal temperature rhythm. PMID- 1753466 TI - Does triazolam change the human circadian rhythms? PMID- 1753467 TI - Bright lights accelerate the re-entrainment of circadian clock to 8-hour phase advance shift of sleep-wake schedule: 1) Circadian rhythms in rectal temperature and plasma melatonin level. PMID- 1753468 TI - Effects of bright light on sleepiness at night. PMID- 1753469 TI - Circadian rhythm disturbance in patients with hypothalamic lesion. PMID- 1753470 TI - Desynchronization of body temperature and blood pressure: circadian rhythms in patients after subarachnoid hemorrhage. PMID- 1753471 TI - Circadian rhythm of melatonin secretion and body temperature in a patient with seasonal affective disorder. PMID- 1753472 TI - Biological rhythm of anorexia nervosa: studies on the body temperature and PSG. PMID- 1753473 TI - Two cases of delayed sleep phase syndrome (DSPS). PMID- 1753474 TI - Vitamin B12 treatment for sleep-wake rhythm disorders. PMID- 1753475 TI - Treatment of persistent sleep-wake schedule disorders in adolescents and vitamin B12. PMID- 1753476 TI - The effects of vitamin B12 on the suppression of melatonin secretion under illumination. PMID- 1753477 TI - Does methylcobalamin (vitamin B12) increase the light sensitivity of human circadian clock? PMID- 1753478 TI - Effect of subchronic administration of methylcobalamin on the acetylcholine and choline content in the brain and locomotor activity in rats. PMID- 1753479 TI - The facilitating effects of vitamin B12 on the re-entrainment of body temperature and locomotor activity rhythms to new light-dark cycle. PMID- 1753480 TI - Seasonal variations of the circadian rhythms in seasonal affective disorder. PMID- 1753481 TI - A case with delayed sleep phase syndrome showing a significant seasonal variation in sleep-wake cycle. PMID- 1753482 TI - Clinical features of seasonal affective disorder in Japan: an interim report for the second year of multicenter collaborative study. PMID- 1753483 TI - Phototherapy of seasonal affective disorder. PMID- 1753484 TI - Seasonal variation of the human circadian rhythms (2) sleep EEG. PMID- 1753485 TI - Effect of the period of light-dark cycle on photoperiodic response in the circadian rhythm of rat behavior. PMID- 1753486 TI - A case of alcoholic dementia with hypomagnesemia and hypocalcemia. AB - A 47-year-old man with chronic alcoholism was admitted to a psychiatric institution because of his mental symptoms and abnormal behavior. He had dementia, emotional disturbances, muscle cramps (tetanic fits), and impairment of abstract thinking and psychomotor function. The biochemical examination of his blood revealed hypomagnesemia, hypocalcemia and a low level of serum parathyroid hormone. The administration of Ca lactate improved hypocalcemia and muscle cramps, but not the other symptoms. An addition of Mg sulfate did not change the clinical condition and the serum electrolyte level. From these findings a relation of chronic alcohol intake to the imbalance of serum electrolytes as well as a low level of serum parathyroid hormone was discussed, and a pathogenetic mechanism of dementia observed in this case was speculated. PMID- 1753487 TI - Computerized tomographic study on the brain of patients with alcohol dependence. AB - One hundred ten patients with alcohol dependence and 56 psychiatric patients with either senile dementia, amphetamine psychosis, epilepsy or chronic schizophrenia were investigated with a CT scan of the brain. The maximum width of the 3rd ventricle was measured, and the presence/absence of enlargement of the lateral ventricle and of atrophy of the frontal lobe was determined independently by 3 physicians. The width of the 3rd ventricle in alcoholic and the other patients examined was gradually enlarged with aging, and the width in these patients was significantly larger than that in the age-matched control patients who were selected from the patients with amphetamine psychosis, epilepsy or schizophrenia. The enlargement of the lateral ventricles observed in the alcoholic patients always accompanied the enlargement of the 3rd ventricle, but not vice versa. The alcoholic patients with frontal lobe atrophy showed a higher incidence of withdrawal delirium than the patients without atrophy. These findings suggest that the chronic intake of alcohol might affect primarily the area around the 3rd ventricle, resulting in enlargement of this ventricle and consequential enlargement of the lateral ventricles and also that the alcoholic patients with frontal lobe atrophy could have a high risk for a manifestation of alcoholic withdrawal delirium. PMID- 1753488 TI - Comparison of body temperature rhythms between healthy elderly and healthy young adults. AB - The fact that the elderly are usually aware of early sleep onset and early morning awakening shows that the phase of sleep-wake rhythms in the elderly is more advanced than that in young adults. Since it has been suggested that human sleep onset, morning awakening, sleep period and depth of sleep are highly influenced by body temperature rhythms, rectal temperature rhythms were analyzed in 7 healthy elderly and 7 healthy young adults under the condition with time cue. Although a significant 24-hour period was found in the rhythms for all subjects, the phase of the rhythms in the elderly was more advanced than in the young adults. Moreover, a significant inverse correlation was observed between age and acrophase time in the elderly. PMID- 1753489 TI - Methylphenidate and interpersonal relationships of children with attention deficit hyperactivity disorder. AB - In order to clarify the effects of methylphenidate on interpersonal relationships of children with attention deficit hyperactivity disorder (ADHD), data from sociometric tests conducted in 28 classes to which ADHD children belonged was analyzed, comparing patients who had a history of methylphenidate treatment with those who had not. It was suggested that ADHD children with a history of methylphenidate treatment had more favorable votes and fewer unfavorable ones than those without it. However, there were more isolated children among ADHD children with methylphenidate treatment than in those without it. The results are discussed in the light of previous findings in the literature and a hypothesis for methylphenidate induced isolation is proposed. PMID- 1753490 TI - Linkage analysis of affective disorder using DNA markers on chromosomes 11 and X. AB - We have investigated two pedigrees in an attempt to detect the putative linkages between affective disorder and c-Ha-ras-1 oncogene and the insulin gene on chromosome 11, or hypoxanthine phosphoribosyltransferase (HPRT) on X chromosome. The linkage between affective disorders and the markers on chromosomes 11 and X was ruled out with the assumption of no recombination. PMID- 1753491 TI - Abnormalities in event-related potentials, N100, P200, P300 and slow wave in schizophrenia. AB - Event-related potentials were recorded in 54 schizophrenics and 88 age-matched controls during a two-tone discrimination (odd ball) task. All the subjects were free from medication. In the schizophrenics, the mean amplitudes of the N100, P300 and Slow Wave latency ranges were decreased, and the amplitude of the P200 latency range was greater than that for the controls. These reductions and the increase were found both for the ERPs elicited by rare target stimuli and for those elicited by frequent nontarget stimuli. The peak latency of N200 to rare stimuli was more prolonged in the schizophrenics than in the controls. This finding confirms the prolongation of N200 latency that Brecher et al. (1987) found for a different visual stimuli task. Neither the N100 nor P300 latency differed between the two groups. PMID- 1753492 TI - Clinical variants of tardive dyskinesia in Japan. AB - Involuntary movement disorders were investigated in a psychiatric hospital in Japan. The prevalence of tardive dyskinesia was 9.9% and four clinical variants of tardive dyskinesia could be classified. Of the 716 patients, tardive dystonia was identified in 15 cases, tardive akathisia in one, respiratory dyskinesia in two and rabbit syndrome in 17. The existence of tardive forms for acute dystonic reactions and akathisia suggests that any type of acute extrapyramidal symptoms can have a tardive form. PMID- 1753493 TI - Depression antedating the onset of Parkinson's disease. AB - Neurological and depressive symptoms in a subtype of Parkinson's disease (PD), in which a depressive state precedes the clinical manifestation of neurological symptoms, were examined on the basis of clinical observations for 3 years or more. PD, in which depression preceded, was different from PD with preceding neurological symptoms, in the severity of not only neurological but also depressive symptoms. These results suggest that PD in which depression precedes neurological symptoms is a specific subtype of PD. It was speculated that the differences in clinical symptoms might be due to a biological background, in particular the dopaminergic system. PMID- 1753494 TI - Vascular changes in the brains with Alzheimer's disease. AB - Sections of temporal and occipital cortex from 14 patients with Alzheimer's disease were examined by light and electron microscopy. Especially, areas without senile plaques or neurofibrillary degeneration were examined in detail. The initial change in the cerebral cortex occurred in the capillaries. The endothelial cells demonstrated degeneration with hypertrophic distorted basement membranes and swelling of the vascular feet. Lipochromes were found in the processes and cell bodies of the astrocytes. A decrease in the number of nerve cells and their processes noted in the cortices may be due to primary vascular degeneration. Severe dementia in Alzheimer's disease may be related to the histopathological findings of diffusely destroyed nerve cells and their processes. PMID- 1753495 TI - Ultrastructure of senile plaque using thick sections in the brain with Alzheimer's disease. AB - The subjects used in the present study consisted of 8 cases with Alzheimer's disease. Senile plaques which seemed to have no relation with the capillaries were examined in thick serial sections (3,000-5,000 A) by electron microscope. The results obtained were as follows: All of those senile plaques had amyloid angiopathy with amyloid fibrils and these amyloid fibrils formed the main elements of senile plaques. From these findings, it was confirmed that the amyloid fibrils in all plaques are produced from the capillaries. PMID- 1753496 TI - Ultrastructure of neurofibrillary tangles in Alzheimer's disease by means of tilt stage electron microscopy. AB - Neurofibrillary tangles (NFT) in the brains of patients with Alzheimer's disease were examined by means of tilt-stage electron microscopy. Observing a longitudinal direction, constricted parts of the NFT did not move in an axial direction. In a transverse section, a fibril of the NFT consisted of globular subunits having a hollow structure in the center and did not appear as paired filaments. From these findings, it was considered that a fibril of NFT consists of twisted protofilaments made up of globular subunits and does not consist of paired helical filaments. PMID- 1753497 TI - [Respiratory tract infection and immunodeficiency]. AB - Many defense mechanisms are located in the respiratory tract, since they are constantly exposed to a variety of pathogens from both inside and outside the body. Among the various defense mechanisms, the immune system is so potent that immunodeficiency results in proneness to infections and repeated and/or intractable infection. It is not uncommon to encounter patients with congenital immunodeficiency in clinical practice because of recent advances in supportive therapy. This paper describes cases of primary immunodeficiency that developed respiratory infections, together with the results of investigations of their immune status. Doctors should suspect the possibility of immunodeficiency in patients with repeated or intractable respiratory infections. Intractable respiratory infections, however, have been seen with increasing frequency in the elderly because of the increase in the elderly population. One reasons for this is the physiologic immunodeficiency associated with aging, which is characterised by decreased antigen-induced lymphocyte proliferation, IL-2 production, IL-2R expression, hsp 70 mRNA production, and demethylation of T lymphocytes, and delayed degradation of c-myc mRNA. PMID- 1753498 TI - [Management of respiratory diseases in the elderly]. AB - Aspiration pneumonia is the fourth cause of death in Japanese, of which 92% occurs in elderly people aged more than 65 years. Pneumonia in the elderly is mostly due to aspiration. Aspiration is caused by disturbance of the pharyngeal reflex and cough mechanisms are due to disturbances of brain activity. Respiratory diseases including bronchial asthma must be treated with consideration of brain activity. PMID- 1753499 TI - [Immunohistochemical findings in resected lung cancer]. AB - The relationship between histological type and immunohistological findings was studied in total 141 cases of resected lung cancer. Adenocarcinoma was cytologically subtyped according to the ultrastructural findings. Immunohistochemical staining was performed on paraffin-embedding tissue using the avidin-biotin-peroxidase complex method for carcinoembryonic antigen (CEA), keratin, secretory component (SC), neuron specific enolase (NSE), lysozyme (Ly) and lactoferrin (La). Adenocarcinoma stained strongly positive with antibody against CEA and SC. There was no statistical difference among the different subtypes of adenocarcinoma, but in the cases of clara cell type, CEA staining was less intense and in goblet cell type, the intensity of SC staining was great. Goblet cell type characteristically stained positively with anti-Ly antibody, and Ly was a specific marker for differentiating adenocarcinoma of goblet cell type. La was positive not only in bronchial gland cell type, but also in other subtypes in adenocarcinoma. Squamous cell carcinoma showed more intense staining with anti keratin antibody than other histological types. Small cell carcinoma extensively stained with anti-NSE antibody, but some of the other histological types also stained positively. NSE was a relatively good marker for small cell carcinoma but was not specific. It is concluded that immunohistochemical examination is a useful method for differentiation of different histological types of lung cancer. PMID- 1753500 TI - [Changes in respiratory resistance and dynamic compliance induced by histamine in the guinea pig]. AB - Respiratory resistance and dynamic compliance in guinea pigs were measured by pulmonary mechanics analyzer Buxco Model 6. Changes induced by intravenous injection of histamine were studied. Administration of histamine caused dose dependent increase in respiratory resistance and decrease in dynamic compliance in guinea pigs. The increase in respiratory resistance by repeated injections of the same dose of histamine was maintained at the same level 5 hours after the first injection. However, the decrease in dynamic compliance by histamine administration decreased significantly from 1 to 4 hours after the first injection. The baseline resistance increased from 1 to 5 hours after the first injection of histamine. The baseline compliance decreased from 1 to 5 hours after the first injection. PMID- 1753501 TI - [Lung function following sleeve bronchoplastic lobectomy for bronchogenic carcinoma]. AB - Twenty-five patients who underwent upper sleeve lobectomy for lung cancer were studied by spirometric examination to evaluate postoperative pulmonary function, including Vital Capacity (VC), %Vital Capacity (%VC), Forced Expiratory Volume in one second (FEV1.0), and Forced Expiratory Volume in one second as a percentage of the forced vital capacity (FEV1.0%). The results of the patients with bronchoplasty were compared with those of patients with lobectomy alone and of patients with pneumonectomy. Lung function was periodically examined postoperatively following bronchoplasty. VC, %VC and FEV1.0 were decreased postoperatively in the patients with upper sleeve lobectomy, while FEV1.0% was increased. There were no differences in postoperative %VC or FEV1.0% between the patients with bronchoplasty and those with upper lobectomy alone. However, the postoperative %VC of the patients with pneumonectomy was significantly decreased compared with patients who underwent postoperative %VC of the patients with pneumonectomy was significantly decreased compared with patients who underwent bronchoplasty or lobectomy alone. %VC in the patients with bronchoplasty was decreased at 3 months after operation, but it to gradually returned to the preoperative value by 13 to 24 months after operation. PMID- 1753503 TI - [Longitudinal analysis of a four-year follow up of pulmonary function development in children with a past history of asthma]. AB - In order to longitudinally study the pulmonary function development of children with a history of asthma, we measured the flow-volume curves of 441 fourth-grade children in seven primary schools randomly selected from the Kashima district in Ibaraki prefecture in 1980, and again in 1982 and 1984. Levels and slopes of pulmonary function indices for individual children were calculated in 325 children who performed acceptable forced expiratory maneuvers at all of the three surveys. In FVC and FEV1, no significant difference of levels and slopes was observed between children with asthmatic history and control children. However, the level and slope of V25 of children with asthmatic history were significantly lower than those of control children (0.5 l/sec for the level, 0.08 l/sec for the slope) even when only those who did not suffer from wheezing attack during the follow-up period were concerned. These results suggested that the functional change of peripheral airways in children with asthmatic history did not recover within a couple of years even when they were in remission. Moreover, the functional differences between those two groups of children might become larger in early adolescence. PMID- 1753502 TI - [Lung injury in idiopathic pulmonary fibrosis and measurement of immunoreactive neutrophil elastase and alpha 1-protease inhibitor in blood]. AB - Idiopathic pulmonary fibrosis (IPF) is thought to develop through slowly progressing lung injury, in which fibrosis occurs as a result of abnormal repair processes. Lung injury in emphysema, in which the normal extracellular matrix is destroyed, is considered to occur mainly because of protease-antiprotease imbalance. In order to examine whether the pathogenesis of IPF involves the proteolytic mechanism of enzymes as in emphysema, concentrations of plasma neutrophil elastase and serum alpha 1-protease inhibitor were measured in patients with IPF, and compared with the levels in patients with emphysema and in normal individuals. In some patients with IPF, the blood concentration of neutrophil elastase was much higher than normal and the degree of imbalance between neutrophil elastase and alpha 1-protease inhibitor was significantly great than in patients with emphysema. In these patients, many years had passed since the onset of the disease, the number of leukocytes and neutrophils and the concentration of LDH in peripheral blood were significantly higher than normal, and the concentration of CEA-II was slightly increased. These data suggest that chronic, massive lung injury had occurred. The blood concentration of neutrophil elastase and alpha 1-protease inhibitor ratio may be useful in assessing the degree of lung injury. PMID- 1753504 TI - [Effects of differently composed liposomes on pulmonary arterial pressure in sheep--involvement of pulmonary intravascular macrophages]. AB - The authors previously reported that liposomes, when injected intravenously, produce transitory pulmonary hypertension with increased secretions of thromboxane A2 from activated intravascular macrophages that phagocytize liposomes in sheep. In the present study, we attempted to determine whether such responses were modified by the lipid compositions of the liposomes. Five different types of liposomes were prepared by reverse-phase evaporation. The liposomes used were composed of phosphatidylcholine (PC), cholesterol (CHOL), and either phosphatidylglycerol (PG-liposomes), phosphatidylserine (PS-liposomes), phosphatidylethanolamine (PE-liposomes), stearlyamine (SA-liposomes) or none (PC liposomes). The net charges of PG and PS-liposomes were negative, SA-liposomes were positive, PE- and PC-liposomes were neutral. Each liposome was injected intravenously to obtain a pulmonary arterial pressure response. Arterial blood was sampled before and after liposome injections to measure thromboxane B2 concentrations. All liposomes, but not PC-liposomes, produced pulmonary arterial hypertension associated with increased arterial thromboxane B2 concentrations, irrespective of the net surface charge of the liposome. PG and PS-liposomes, both of which were negatively charged, showed different dose-response curves, the two different types of neutral liposomes showed different responses, and PC-liposomes produced a small increase in pulmonary arterial pressure. PE-liposomes produced marked increases in the pulmonary arterial pressure. From these results, the authors concluded that pulmonary arterial pressure responses to the liposomes are modified by the lipid compositions of the liposomes, and that this is not caused by the difference in the net charge of each liposome. PMID- 1753505 TI - [Etiological examination of idiopathic interstitial pneumonia and lung cancer in autopsy cases]. AB - In order to investigate the etiology of usual interstitial pneumonia (UIP) and UIP with lung cancer (LC), autopsy findings in 18 cases of UIP with LC and 11 cases of uncomplicated UIP were clinicopathologically compared with the environmental factors of smoking habits and occupation. UIP with LC was highly correlated with smoking, especially heavy smoking and with occupations in which dust is inhaled, such as electrical installation and ceramic production, indicating that these environmental factors are important background factors in the complication of UIP with IC. Pathologic examination of cases of UIP with LC (6 squamous cell carcinomas, 5 small cell carcinomas, 4 adenocarcinomas, and 3 large cell carcinomas, 2 of which showed pulmonary double carcinoma revealing a slight correlation between fibrosis and primary site of LC and a slightly greater correlation of squamous cell carcinoma and small cell carcinoma to smoking habits and inhalation of dust. In terms of the correlation between UIP and LC among autopsy cases, the environmental factors proved to be more significant than the fibrotic findings. These environmental factors are thought to merit consideration as common predisposing factors in the development of LC and its complication with UIP. PMID- 1753506 TI - [Nucleolar organizer regions, nuclear DNA content, and proliferative activity in adenocarcinoma of the lung]. AB - The relationship between the quantity of silver-binding nucleolar organizer regions (AgNORs), nuclear DNA content, and proliferative activity was studied in 61 patients with adenocarcinoma of the lung. The proliferative activity of adenocarcinoma was estimated by tumor volume doubling time based on chest X-ray findings. There was a high, inverse correlation between the AgNORs and the tumor doubling time (p less than 0.001, r = -0.815), and the contribution rate was high value (2 = 0.664). However, the AgNORs value was an independent prognostic factor for survival time. A better 5-year survival rate was observed in patients with DNA diploidy than in DNA aneuploidy, but there was no statistical difference between the two groups. There was an inverse correlation between the DNA index and tumor doubling time (p less than 0.05, r = -0.565), but the contribution rate had a low value (r2 = 0.319). These results indicate that the AgNORs value is important in providing an estimate of the proliferative activity of adenocarcinoma. PMID- 1753507 TI - [Percutaneous instillation of fluconazole in the treatment of pulmonary aspergilloma]. AB - A 68-year-old woman had pulmonary aspergilloma in the right upper lobe with old cavitary pulmonary tuberculosis. Despite intravenous fluconazole there was no change in the size of the fungus ball. Endobronchial instillation of fluconazole also failed. Subsequently percutaneous instillation of fluconazole was attempted with localized drainage. The fungus ball decreased in size after 8 weeks. Although slight hemoptysis and subcutaneous emphysema occurred in this case, these condition required no treatment. This method of treatment appears to be useful for inoperable cases of pulmonary aspergilloma. PMID- 1753508 TI - [Fulminant mycoplasma pneumoniae infection presenting with Stevens-Johnson syndrome & respiratory failure]. AB - An 18-year-old man was admitted to Hamamatsu University Hospital on February 15, 1985, with high fever, vesicular and papular rash involving the skin and mouth, conjunctivitis, productive cough and dyspnea. A diagnosis of Stevens-Johnson syndrome was made by skin biopsy, and chest X-ray showed an infiltrate in the right lower lung filed. Despite treatment with corticosteroids and antibiotics, the mucocutaneous lesions did not heal, and the pneumonia progressed to both lung fields. Because the patient had developed dyspnea, a tracheotomy was performed, mechanical ventilatory support was instituted, and high-dose corticosteroid therapy was started. However, jaundice due to intrahepatic cholestasis, hematuria, hematochezia, sepsis, and subcutaneous and mediastinal emphysema ensued, and the patient died of respiratory failure on March 1. Postmortem examination of the lung demonstrated diffuse alveolar damage. The complement fixation titer for Mycoplasma was 1:64, compared with a level of less than 1:4 on admission. This case was though to be one of fulminant Mycoplasma pneumoniae infection presenting with Stevens-Johnson syndrome, respiratory failure and other extra-pulmonary complications. PMID- 1753509 TI - [A case of chest wall rhabdomyosarcoma]. AB - A 56-year-old man was admitted to our hospital with right chest pain. Chest X ray, CT scan and MRI revealed a chest wall tumor and enlarged mediastinal lymph nodes. Percutaneous lung biopsy was performed, and the pathological diagnosis of pleomorphic rhabdomyosarcoma was obtained. The only significant abnormal laboratory finding was elevation of serum NSE (24.5 ng/ml). Although chemotherapy (VAC-ADM) and radiation therapy were performed, the patient died about 7 months after admission. To our knowledge, only 17 cases of chest wall rhabdomyosarcoma have been reported in Japan. PMID- 1753510 TI - [A case of Swyer-James syndrome diagnosed by selective alveolobronchography]. AB - A 33-year-old male was admitted to our hospital for further investigation of unilateral hyperlucency of the left upper and middle lung fields on chest X-ray. A pulmonary scan showed decreased perfusion of the left upper and middle lung fields. Pulmonary arteriography demonstrated small left pulmonary arteries with diminished peripheral vascular branches. Left bronchogram showed almost normal distribution of main and subsegmental bronchi, but poor filling by contrast in the peripheral bronchi. From these findings, the patient was diagnosed as having Swyer-James syndrome. In order to demonstrate the alveoli in this syndrome, selective alveolobronchography (SAB) was performed. SAB revealed coarse ring shadows of B1+2. PMID- 1753511 TI - [A case of hypereosinophilic syndrome followed by bronchial asthma, intraventricular thrombus, and duodenitis]. AB - We report a 43-year-old male with hypereosinophilic syndrome. The patient has had eosinophilia since the age of 25. He developed bronchial asthma at 41 years of age. In the following year, he consulted a gastroenterologist because of fever and abdominal discomfort. Upper gastrointestinal study showed duodenitis. At the age of 43 years, there was slight fever, watery diarrhea, and eosinophilia. Examination in our department disclosed hypereosinophilic syndrome associated with duodenitis, endomyocarditis with an intraventricular thrombus, and bronchial asthma caused by house dust. Both prednisolone and aspirin were administered with improvement of eosinophilia and partial thrombolysis. Assays of IL-3, GM-CSF, and IL-5 revealed increased activity of IL-5, GM-CSF, and IL-3 in this order. Especially IL-5 has by far the strongest activity in these cytokines. IL-5 may play an important role in the development of hypereosinophilic syndrome. PMID- 1753512 TI - [A case of eosinophilic granuloma of the cervical lymph nodes associated with pulmonary cystic lesions]. AB - A 33-year-old man was referred to our department because of left cervical lymphadenopathy for one month which did not respond to antibiotics. Histological examination of the lymph node biopsy revealed eosinophilic granuloma. However, repeated bronchoscopic examinations performed to evaluate the pulmonary lesions appearing on chest roentgenograms and chest CT scans revealed no evidence of eosinophilic granuloma. Steroid therapy resulted in resolution of the cervical lymphadenopathy, but the pulmonary lesions showed no response. The possible relationship between eosinophilic granuloma and pulmonary cystic lesions in our patient is discussed. PMID- 1753513 TI - [A case of Kearns-Sayre syndrome with impaired respiratory regulation]. AB - We reported a case of Kearns-Sayre syndrome with impaired respiratory regulation. A 55-year-old male was admitted to our hospital complaining of chronic progressive external ophthalmoplegia, limb muscle weakness and dyspnea. On admission, because arterial blood gas analysis showed marked alveolar hypoventilation, ventilatory response was measured and diminished chemosensitivity to both hypoxia and hypercapnia was found. His vital capacity and forced expiratory volume in 1 second were slightly decreased, and a chest X ray film revealed a moderate degree of elevation of the bilateral diaphragm. Therefore, we considered that the diminished response to hypoxia and hypercapnia in this case was caused by an impairment of the respiratory center, as well as chemoreceptors and also the presence of respiratory muscular weakness. PMID- 1753514 TI - [A case of chronic pulmonary emphysema with a past history of bilateral carotid body resection]. AB - A 76-year-old man, whose carotid bodies had been resected for treatment of bronchial asthma 40 years previously was admitted for evaluation of abnormal arterial blood gases and exertional dyspnea. The case was diagnosed clinically as chronic pulmonary emphysema. His peripheral chemoreceptor function, estimated by hypoxic ventilatory and P0.1 response tests and withdrawal test was non functioning. His PaCO2 value tended to rise over 50 Torr either after light exercise or during airway infection, though it was normal at rest. In addition his dyspnea had continued for 40 years in spite of carotid body resection. It was concluded that the effect of carotid body resection lasts more than 40 years and it does not have a good effect on COPD. PMID- 1753515 TI - [Superior vena cava syndrome as initial symptom of Vasculo-Behcet's disease--case report]. AB - A 26-year-old woman with a history of recurrent spontaneous abortion was admitted because of superior vena cava syndrome. Chest computed tomography and digital subtraction angiography revealed obstruction of the superior vena cava by a thrombus. After admission she also developed oral aphthous ulceration, erythema nodosum, and positive cutaneous hypersensitivity reaction to intradermal injection of saline. Laboratory investigations revealed HLA-B51 and positive lupus anticoagulant. We made the diagnosis of Vasculo-Behcet's disease and treated her with heparin and urokinase with no clinical improvement. The fever subsided after prednisolone administration. Two years later, superior vena cava syndrome had slightly improved, although RI venography showed complete obstruction of the superior vena cava with development of collateral circulation. Endoscopic examination showed downhill esophageal varices. It is of note that the initial symptom in this case of Vasculo-Behcet's disease was superior vena cava syndrome, and that lupus anticoagulant may have contributed to the thrombus formation. PMID- 1753516 TI - [A case of pulmonary varices in which enhanced CT was useful for diagnosis]. AB - A case of pulmonary varices in a 73-year-old female is presented. Routine chest X ray revealed a mass in the right hilar region. CR tomogram showed a round, clearly defined mass at the right hilum. Computed tomography demonstrated marked enlargement of the proximal portion of the pulmonary vein at the entrance of the left atrium, which was suspected to be pulmonary varices. The diagnosis was confirmed by pulmonary angiography. During the arterial phase no abnormal findings were seen, but during the venous phase the veins of the right upper and middle lobes were found to be draining into the dilated pulmonary vein and then into the left atrium. Thus, the diagnosis of pulmonary varices was established. CT and angiography are the most useful methods for definitive diagnosis of pulmonary varices. PMID- 1753517 TI - [An electron microscopic study of the pulmonary alveolar capillaries in idiopathic interstitial pneumonia and lungs of collagen vascular diseases]. AB - The ultrastructure of pulmonary alveolar capillaries in idiopathic interstitial pneumonia (IIP) and collagen vascular diseases (CVD) were investigated. In IIP, the endothelial cells were only slightly swollen. The basement membrane (BM) was moderately thickened. In CVD, swelling of the endothelial cells and thickening of the BM were more severe than those of IIP. The injury of the endothelial cells seemed to be more severe than IIP. The patients with PSS and MCTD revealed degeneration of endothelial cells as well as lamellation of BM. The endothelial cell damage was most severe among CVD cases, and these changes were assumed to induce pulmonary hypertension. Microtubular structures were observed in the endothelium of SLE, dermatomyositis, polymyositis, PSS and MCTD patients. Weibel Palade bodies and increase of pericytes were noticed in PSS and MCTD patients which seemed to be related to endothelial injuries. No electron-dense deposits were observed in any case. PMID- 1753518 TI - [Evaluation of immunity based on bronchoalveolar lavage fluid in patients with pleural plaque in the chest X-ray]. AB - Alveolar and lower respiratory tract immunity in addition to systemic immunity in 31 patients with pleural plaques found on chest X-rays were evaluated. All cases had occupational histories of asbestos exposure, but ferruginous bodies in BAL fluid were only detected in 21 of 31 cases. The percentage of cell components in BAL fluid was evaluated according to the number of ferruginous bodies found in the BAL fluid. As the number of ferruginous bodies increased, neutrophils and T lymphocytes decreased, but B lymphocytes increased. Furthermore, CD25-positive cells were remarkably increased in patients with high exposure to asbestos. In addition, CD25-positive cells in the peripheral blood and serum soluble IL-2 receptors were elevated in the patients with high exposure to asbestos. PMID- 1753519 TI - [A case of Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure]. AB - The authors report a 56-year-old woman with Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure. Five days before admission, she experienced right otalgia and right facial pain and consulted an otolaryngologist of our hospital, who diagnosed the illness as acute parotitis and laryngopharyngitis. One day before admission, she experienced mild dyspnea and general fatigue and came to our hospital emergency room. A chest X-ray film revealed no abnormalities but some blisters were observed around her right ear. The next day, her dyspnea became more severe and she was admitted. A chest X-ray film on admission revealed right lower lobe consolidation, and neurological examination disclosed multiple cranial nerve paralysis, i.e., paralysis of the right fifth, seventh, eighth, ninth, tenth, eleventh, twelfth and left tenth cranial nerve. The serum titer of anti-herpes zoster antibody was elevated to 1,024, and the patient was diagnosed as having Ramsey Hunt syndrome with multiple cranial nerve paralysis. Arterial blood gas analysis revealed hypoxemia with hypercapnea, which was considered to be due to aspiration pneumonia and central airway obstruction caused by vocal cord paralysis. Mechanical ventilation was soon instituted and several antibiotics and acyclovir were administered intravenously, with marked effects. Three months after admission, the patient was discharged with no sequelae except mild hoarseness. Patients with herpes zoster oticus, facial nerve paralysis and auditory symptoms are diagnosed as having Ramsey Hunt syndrome. This case was complicated by lower cranial nerve paralysis and acute respiratory failure, which is very rare.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753520 TI - [Leiomyosarcoma of the esophagus associated with pulmonary edema by the compression of the left atrium]. AB - Leiomyosarcoma of the esophagus is a rare neoplasm. We reported a very rare case of esophageal leiomyosarcoma associated with pulmonary edema by the compression of the left atrium. A 67-year-old man was admitted with a 3-month history of chest pain, exertional dyspnea and dysphagia. Chest X-ray computed tomography showed posterior mediastinal tumor. Esophageogastroscopy and fiberoptic bronchofiberscopy showed no direct invasion of the tumor. By echocardiography, the left atrium was found to be compressed by the tumor and pulmonary hypertension (58/25 mmHg) and increased pulmonary wedge pressure (25 mmHg) was present. Open biopsy specimen demonstrated elongated cells suggestive of sarcoma. At autopsy, the tumor was confirmed to be leiomyosarcoma and to be originated from the lower esophagus. PMID- 1753521 TI - [A case of paragonimiasis Miyazakii with bilateral pleural and pericardial effusion]. AB - A 38-year-old man was admitted to our hospital for further examination of bilateral pleural and pericardial effusion. He had complained of dyspnea on exertion occurring six months after ingestion of raw freshwater crabs, Patomon dehaani. X-ray films and CT scan of the chest taken on admission revealed massive bilateral pleural and pericardial effusion. High serum IgE level and eosinophilia were noted on laboratory examination. Antibody against Paragonimus Miyazakii antigen was detected in patient's serum as well as pleural and pericardial fluids by the Ouchterlony test. The patient was treated effectively by Bithionol. PMID- 1753522 TI - [A case of prolonged eosinophilic pneumonia with pulmonary emphysema and bronchial asthma diagnosed by open lung biopsy]. AB - A 65-year-old man was admitted to our hospital complaining of productive cough, dyspnea and stridor. Chest X-ray disclosed overinflation with micronodular infiltrates. Blood examination showed mild eosinophilia and IgE elevation. Pulmonary function test disclosed severe airway obstruction and diffusion capacity impairment. Although clinical improvement was achieved after bronchodilator therapy, laboratory abnormalities continued. Open lung biopsy demonstrated mononuclear cellular and eosinophilic infiltration at alveolar lumen and vessel walls without prominent fibrosis, which was compatible for prolonged eosinophilic pneumonia. From above findings, this case was thought as a prolonged eosinophilic pneumonia combined with pulmonary emphysema and bronchial asthma. PMID- 1753523 TI - [A case of diffuse aspiration bronchiolitis secondary to achalasia of the esophagus]. AB - A 12-year-old male was admitted to our hospital because of cough, sputum and increasing fever. Chest CT revealed ill-defined small round opacities located around the end of the bronchovascular branchings in almost all of the lung fields. These findings were compatible with diffuse panbronchiolities (DPB). On the other hand, the boy was diagnosed as having achalasia of the esophagus and fragments of food were observed in the bronchi by bronchoscopy. Repeated aspiration and infection due to achalasia are factors which brought about diffuse aspiration bronchiolitis (DAB). PMID- 1753524 TI - [A case of theophylline-induced rhabdomyolysis following therapy of bronchial asthma]. AB - A case of a 81-year-old asthmatic male with Theophylline-induced rhabdomyolysis was reported. After intravenous administration of 250 mg of Aminophylline, he developed muscle weakness in the lower extremities. Serum CPK was 31,450 IU, and other enzymes escaping from skeletal muscles were elevated. Serum and urine myoglobin were also elevated. Cessation of Theophylline administration and conservative therapy resulted in improvement of rhabdomyolysis without concomitant acute renal failure. The present case was the 11th case of Theophylline-induced rhabdomyolysis in the world and the second case Japan. PMID- 1753525 TI - [Multiple pulmonary metastasis from histologically benign giant cell tumor of the right radial olecranon]. AB - An unusual case of a benign giant cell tumor of bone with pulmonary metastasis is reported. A 23-year-old man had a painful tumor in the right radial olecranon that proved to be a histologically benign giant cell tumor. Curettage and bone grafting were performed, but the tumor recurred twice, 8 months and 20 months after initial treatment. Histological examination of biopsy materials from the recurring tumor showed typical benign giant cell tumors. Five years later, wedge resections were performed for bilateral pulmonary nodules, which had been detected by chance. The pulmonary nodules turned out to be histologically similar to the primary tumor of the olecranon. Almost 7 years later, he was asymptomatic and the chest radiograph was clear, and there was no local recurrence of the lesion. PMID- 1753526 TI - [Immunohistochemical and electromicroscopic study of a case of primary nodular pulmonary amyloidosis]. AB - A 41-year-old man was hospitalized for further evaluation of an abnormal chest films which revealed a nodular shadow in the right middle lung field, which remarkably enlarged during one year. As no diagnostic procedures ruled out lung carcinoma of right S6, a right lower lobectomy was performed. Pathologically the nodules were composed of amorphous and eosionphilic materials which were diagnosed as amyloid by Congo-red stain and electron microscopic examination. Since there were no deposits in other organs and there was no abnormality of serologic and urinary protein analysis, a diagnosis of primary nodular pulmonary amyloidosis was established. PMID- 1753527 TI - [A case of pulmonary eosinophilic granuloma diagnosed by TBLB]. AB - A case of pulmonary eosinophilic granuloma which was diagnosed by TBLB was presented. A 24-year-old male was admitted complaining of cough and fever of unknown etiology. He had a history of fever which had disappeared spontaneously 9 months previously. Laboratory examinations including blood gas analysis and pulmonary function tests showed no significant abnormalities. Chest roentgenogram showed faint linear opacities. Computed tomography revealed multiple small cysts and small nodular lesions mainly in the upper lung field. CT findings were strongly suggested pulmonary eosinophilic granuloma. TBLB was performed and 6 specimens were obtained, of which 4 showed granulomatous lesions consisting of histiocytosis X cell and inflammatory cells with infiltration of eosinophils. Furthermore, granulomatous lesions were positive for S-100 protein staining. The effectiveness of open lung biopsy has been emphasized in the diagnosis of pulmonary eosinophilic granuloma, however, TBLB is also useful for diagnosis, especially in the active or early stage of this disease. PMID- 1753528 TI - [A case report of the limited form Wegener's granulomatosis]. AB - The classical from of Wegener's granulomatosis (WG) is a necrotizing granulomatous angiitis that involves the upper and lower airways, and kidneys. A limited form of WG is characterized by pulmonary lesions identical to those of classical form WG without renal involvement. The authors report a case of limited form WG. A 58-year-old Japanese woman was admitted because of an abnormal pulmonary shadow. Pathological examination revealed granulomatous angiitis consistent with WG. No other organ involvement was found. The pulmonary shadow improved with cyclophosphamide therapy. The patient is now well and without evidence of exacerbation of the disease 18 month after the discharge. PMID- 1753529 TI - [The suppressive effects of smoking on antibody production in experimental hypersensitivity pneumonitis in rabbits]. AB - Farmer's lung disease is one type of hypersensitivity pneumonitis (HP) in dairy farmers, and is usually caused by Micropolyspora faeni (Mf). It has been reported that the positive rate of precipitin antibody to Mf in smoking dairy farmers is one-eighth to one-half of that in nonsmoking dairy farmers. To clarify the mechanism of this phenomenon, by using an experimental HP model in rabbits, we investigated 1) the effects of short (5 weeks) and long (20 weeks)-term cigarette smoke exposure on the antibody formation, 2) the effects of 30 weeks of smoke exposure on the accessory cell function of alveolar macrophages (AM). Smoking exerted variable influences on antibody production, depending on the duration of smoke exposure, and we confirmed that long-term smoke exposure had suppressive effects. In addition AM from smoked rabbits suppressed lymphoproliferative response to autologous spleen cells. It was concluded that in this experimental HP, smoking affects the functions of both AM and lymphocytes, and that it suppresses antibody production as long as the smoke exposure continues. PMID- 1753530 TI - [Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease]. AB - The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek. PMID- 1753531 TI - [Clinicopathological features of metastatic pulmonary calcinosis with malignant neoplasm]. AB - Metastatic pulmonary calcinosis is a rare complication seen in malignancies accompanied by hypercalcemia, or chronic renal failure. We reviewed the clinicopathological findings of 8 cases of metastatic pulmonary calcinosis accompanied malignancy revealed at autopsy. The underlying diseases were malignant lymphoma in 3 cases (adult T cell lymphoma in 2 cases), multiple myeloma in 2, lung cancer in 2, and acute myelocytic leukemia in 1, all cases were complicated by hypercalcemia and renal failure. Chest X-ray revealed almost normal findings in 2 cases, bilateral diffuse infiltrates in 4, bilateral infiltrates in the apex in 1, and right atelectasis in 1. Bone scintigraphy was performed in 4 cases, and revealed warm pulmonary uptake in 1 patient with multiple myeloma and 1 with lung cancer, but normal findings in the 2 other cases. Histopathological examination revealed diffuse alveolar septal edema and fibrosis due to calcium deposition, which were considered to be the cause of respiratory failure. Metastatic pulmonary calcinosis is a rare but a serious complication in malignancies accompanied by hypercalcemia and renal failure, and bone scintigraphy seems to be a useful method for its diagnosis. PMID- 1753532 TI - [Dynamic changes in superior vena caval configuration based on posture]. AB - To noninvasively study positional effects on superior vena caval configuration in humans, endoscopic ultrasonography was performed in 34 subjects including 20 with lung cancer, 5 with esophageal cancer and 9 with other diseases. None of the these subjects had cardiovascular involvement or respiratory dysfunction. A fiberoptic esophagoscope equipped with a 7.5 MHz linear array ultrasonic transducer at its tip (EPE-703, Toshiba-Machida) was used for the study. The actual movement of the superior vena cava (SVC) was clearly observed at the hilar level in all cases. During the cardiac cycle the anteroposterior diameter of the SVC was observed to reach a maximum at the atrial systole and reached a minimum at the late ventricular systole. With respiration, the SVC increased in diameter during inspiration and decreased during expiration. Moreover M and B mode figures of the SVC wall were recorded in left (LLD) and right decubitus (RLD) and supine position (SUP) in 34 subjects. On quiet ventilation of FRC level the diameter of the SVC was unchanged. Both the maximal and minimal diameters of the SVC, which were corrected for body surface area (BSA), were 11.3 +/- 0.3 (mean +/- SEM) mm/m2 and 9.8 +/- 0.3 mm/m2 in right lateral decubitus position, 9.4 +/- 0.3 and 7.9 +/- 0.3 in the supine position, 8.5 +/- 0.3 and 7.1 +/- 0.3 in the left lateral decubitus position, respectively. The size of the SVC was the greatest in the right lateral decubitus position and was the smallest in left lateral decubitus position (p less than 0.01, multiple comparison). It was suggested that the geometry of the SVC is influenced by thoracic pressure and gravity and that it behaves very similarly to pulmonary vascular vessels as a collapsible tube. PMID- 1753533 TI - [Influence of respiratory frequency in measurement of specific airway conductance during non-panting breathing]. AB - In order to investigate the influence of respiratory frequency in the measurement of specific airway conductance (sGaw) during non-panting breathing, we examined specific airway conductance using a body plethysmograph (BX-82, Minato) in 20 stable pulmonary emphysema patients and 19 normal control subjects. Our body plethysmograph device can measure sGaw automatically without panting by making various corrections using a 16-bit microcomputer. We measured sGaw first at a flow of 0.5 L/sec during both inspiratory and expiratory ventilatory phases, then the respiratory frequency was changed from 0.5 to 1.0, 1.5 and 2.0 Hz. In normal control subjects sGaw, tidal volume and mouth flow significantly changed by increasing respiratory frequency, and there was a significant correlation between sGaw and mouth flow. In pulmonary emphysema patients, tidal volume decreased significantly by increasing respiratory frequency, and there was a significant correlation between sGaw and tidal volume, but sGaw and mouth flow did not change significantly by increasing respiratory frequency. These results suggest that specific airway conductance is influenced by respiratory frequency, possibly due to the change in tidal volume and mouth flow. It is necessary to standardize respiratory frequencies and mouth flows in the measurement of specific airway conductance during non-panting breathing. PMID- 1753534 TI - [Adult bronchial asthma in Japan]. AB - The first nationwide research to disclose the actual state of the adult bronchial asthma in Japan covered 2,832 patients who visited hospitals during the time of investigation, and who answered questionnaire. They were asked about their present state of asthma and experience of treatment for acute asthmatic attacks etc. Physicians in various institutions were asked to state their experience regarding corticosteroid therapy for them as well as asthmatic deaths among their patients per year. The male:female ratio was 1,368 (48.3%): 1,464 (51.7%). Concerning age, 24.4% of patients were in their 50s, 22.6% were in their 60s and 56% of patients were in the 30 to 60 age group and 79.8% were adult-onset asthma, a total of 80% needed regular medications and 30% were corticosteroid dependent, what 76.9%, 43.1% and 4.8% of the patients had experienced treatment by DIV, oxygen therapy and controlled ventilation for acute asthmatic attacks, respectively. Among the 3 groups, 59.5%, 51.7% and 24.8 of the patients had experienced of admission to hospital, visiting an emergency rooms at night or being rushed to hospital ambulance of the total, 48.1% were diagnosed as mild asthma, 38.2% as moderate and 12.7% were diagnosed as severe asthma. The 41 deaths due to acute asthmatic attack in one year represented 0.29% of all adult asthmatic patients visiting those hospitals in one year. Deaths at home or on the way to the hospital were much greater in number than after hospitalization. PMID- 1753535 TI - [Sulfuric acid submicron aerosols induce morphological changes in the central airways in the guinea pig]. AB - We examined the airway injury of the guinea pig exposed to sulfuric acid submicron aerosols (1 mg/m3). The animals were exposed to filtered air (sham control) or to submicrometer-sized sulfuric acid aerosols for 4 hr/day, 6 days/week, with sacrifices after 4 hours, 3 days, 1, 2, and 4 weeks of acid exposure. Light and electron microscopic examinations revealed that epithelial injury such as disappearance of cilia in the central airways was observed and the severity of the injury increased with exposure duration. This experimental study shows that submicrometer particles of sulfuric acid induces significant alterations in the central airways and may be involved in the incidence of asthma attack. PMID- 1753536 TI - [Effect of serum albumin concentration on percentage of free theophylline fraction]. AB - The authors experienced three cases in which serum free theophylline concentrations (F) rose with unchanged or decreased serum total theophylline concentrations (T). To clarify the causes of changes in F or T within a short time, we studied the relationship between F and serum albumin concentration or T in patients, and the relationship between T and F using aminophylline alone or aminophylline and cefazoline (CEZ) in rabbits. In patients, the fraction of free theophylline (F/T) showed a reverse relation to the serum albumin concentration, and a positive relation to T. In rabbits, when aminophylline was injected with CEZ, F/T increased in proportion to the dose of CEZ and T decreased when aminophylline alone was injected. The data suggested that F/T increased accompanied with decreasing serum albumin concentration or increasing T, since the albumin binding-site of theophylline is limited. The present study also suggested that the protein-bound theophylline decreased in competition with CEZ, therefore F/T increased when aminophylline was injected with CEZ. It is likely that decreased T is a result of augmented movement of theophylline to the tissue due to decreased serum albumin concentration. To evaluate the clinical conditions of the patients taking theophylline, it is necessary to directly monitor F, or to measure serum albumin concentration if direct measurement of F is not possible. PMID- 1753537 TI - [Effects of antiplatelet serum on the pulmonary intravascular macrophage]. AB - Antiplatelet serum (APS) has been used to investigate the role of platelets in lung injury. However, the effect of APS on pulmonary intravascular macrophages (PIMs) is unknown. Therefore we investigated the effects of APS on PIMs. A bolus injection of APS raised pulmonary arterial pressure with the production of thromboxane. Fluorescence- and electronmicroscopy revealed that PIMs engulfed APS platelets complexes after the APS injection. Repeated injections of APS increased the ratio of PIMs which engulfed platelets and the number of platelets in a PIM, but attenuated phagocytosis of liposomes by PIMs to decrease liposome-induced pulmonary hypertension and production of thromboxane. From the above data it was concluded that APS injection causes PIMs to engulf APS-platelets complexes, and that APS injection attenuates the phagocytosis of liposomes by PIMs, and thereby diminishes liposome-induced pulmonary hypertension and production of thromboxane. PMID- 1753538 TI - [Predictive factors of etiologic agents of community-acquired pneumonia presenting at a district general hospital]. AB - Community-acquired pneumonia is one of the major respiratory diseases causing hospital admission in previously healthy patients. Prompt and appropriate antibiotic selection is essential for recovery. The authors tried to determine the distribution of the etiologic agents of community-acquired pneumonias and to analyze predictive factors. Out of 188 cases of community-acquired pneumonia presenting to our hospital, etiologic agents were determined in 106 cases (56%). Twenty-nine cases were due to Streptococcus pneumoniae, 27 cases due to Mycoplasma, 17 cases due to Haemophilus influenzae and 21 cases due to Mycobacterium tuberculosis. M. tuberculosis was the cause in 11% of all cases and the importance of pulmonary tuberculosis must be emphasized as a community acquired pneumonia. Out of 58 cases under 50 years old, Mycoplasma pneumoniae was the etiologic agent in 23 cases (40%) and S. pneumoniae in 7 cases (12%). Out of 62 cases not less than 70 years old. M. tuberculosis was the most common etiologic agent (15 cases, 24%). S. pneumoniae followed, being causative in 13 cases (21%). M. tuberculosis was the cause in 10 cases out of 31 cases who did not complain of fever at presentation. In 86 cases who did not show leukocytosis on admission, 21 cases were due to Mycoplasma (24%) and 15 cases were due to M. tuberculosis (17%). In particular 17 cases were due to Mycoplasma among 28 cases under 50 years old without leukocytosis (61%), and 11 cases were due to M. tuberculosis in the 27 cases no less than 70 years old without leukocytosis (41%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753539 TI - [Gene analysis of pulmonary lymphoproliferative disorders]. AB - The authors performed gene analysis of pulmonary lymphoproliferative disorders. Cell suspensions were obtained from tissues of malignant lymphoma or pseudolymphoma in Cases 1 to 3. High-molecular-weight DNA was extracted from these specimens, digested with restriction endonucleases, size-fractionated by agarose-gel electrophoresis and transferred by the Southern procedure to nitrocellulose. Hybridization to nick-translated 32P DNA probes of the immunoglobulin JH, C kappa, C lambda, regions, and T cell receptor beta 1 region. In case 1 and 2, which were diagnosed as B cell lymphoma, cells from tumor had rearranged heavy chain genes, clearly establishing the clonal nature. In Case 3, which was diagnosed as pseudolymphoma, the tumor contained clonal immunoglobulin gene rearrangements as detected with both the JH heavy chain and C kappa light chain gene probes. It was concluded that gene analysis is an effective procedure for establishing a diagnosis of lymphoma in neoplastic disorders of uncertain cell type and for detecting clonal T cell or B cell populations with atypical lymphofollicular hyperplasia. PMID- 1753540 TI - [Clinical study on soluble interleukin-2 receptor in patients with sarcoidosis]. AB - Levels of soluble IL-2 receptor in sera of 18 patients with sarcoidosis were measured by a sandwich ELISA method established by the authors and were found to be significantly higher than those in sera of normal subjects. Levels of soluble IL-2 receptor in sera of sarcoidosis cases of bilateral hilar lymphadenopathy (BHL) were significantly higher than those in sera of sarcoidosis cases without BHL. In patients with sarcoidosis, levels of soluble IL-2 receptor did not differ in relation to the presence or absence of ocular lesions, or in relation to positive or negative response to protein purified derivative of tuberculosis (PPD). PMID- 1753541 TI - [Proliferative characteristics of fibroblast lines derived from open lung biopsy specimens of patients with the usual interstitial pneumonia form of idiopathic pulmonary fibrosis]. AB - One form of idiopathic pulmonary fibrosis (IPF), usual intersitial pneumonia (UIP) is characterized pathologically by patchily distributed fibrotic areas in apparently normal parenchyma. Excessive accumulation of collagen and fibroblasts in fibrotic areas are shown histologically. Fibroblast proliferation is generally evaluated as a process following alveolitis. However, substantial alveolitis with increased inflammatory and immune cells were not observed in our UIP cases. To evaluate the possibility that fibroblasts in UIP are controlled by mechanisms other than normal paracrine regulation, proliferative features of lung fibroblast lines from UIP lung with regular growth medium, platelet derived growth factor (PDGF) and prostaglandin E2 (PGE2) were investigated. Ten fibroblast lines from open lung biopsy specimens of patients with IPF (UIP) and 10 control fibroblast lines from surgically resected lung tissues of patients with limited lung disease were established. The doubling time of fibroblast lines with regular growth medium was UIP:32.0 +/- 6.0 hrs. (mean +/- S.D.), normal control: 33.2 +/- 10.4 hrs. There was no difference between the groups. To examine growth promotion activity by PDGF and growth inhibition by PGE2, lung specimens from 4 patients with IPF were subdivided into tissue with high intensity fibrotic lesion (H) and low intensity fibrotic lesion (L), and the fibroblast lines were established separately. 3H-thymidine uptake with or without PDGF and PGE2 was examined, and results were expressed as the stimulation index. Growth promotion by PDGF was H: 1.97 +/- 1.19, L: 1.89 +/- 0.78, normal control: 2.29 +/- 0.55. There were no differences between groups. Growth inhibition by PGE2 was H: 0.88 +/- 0.24, L: 0.69 +/- 0.49, normal control: 0.44 +/- 0.33. Growth inhibition for H was significantly lower than control (p less than 0.05). Growth inhibition for L was lower than controls, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753542 TI - [Quantitative evaluation of regional blood flow in pulmonary sarcoidosis with bull's eye analysis]. AB - Lung perfusion scintigraphy was performed in 23 patients with pulmonary sarcoidosis and in 11 normal volunteers. Bull's eye analysis was used to analyze regional pulmonary blood flow quantitatively. First, whole lung perfusion images were divided into three regions by three concentric circles. Then radial axes were projected from the center to define 36 x 10 degrees sectors. The counts for each sector were calculated and a Bull's eye image was displayed. The counts were compared with the lower limit of normal (mean - 2SD), and as the indices of reduction in perfusion, extent score (ES) and severity score (SS) were calculated. ES and SS showed significant reduction in perfusion 16 patients (70%) with sarcoidosis. In stage II sarcoidosis, both ES and SS were significantly higher than in stage I sarcoidosis (p less than 0.05). In comparison with the findings of transbronchial lung biopsy, both ES and SS had correlations with the degree of alveolitis and ES had a correlation with the degree of angiitis. Both ES and SS have no correlation with 67Ga scintigraphy findings. In comparison with clinical data, ES had a positive correlation with serum angiotensin-converting enzyme activity (p less than 0.05), and SS had a significant positive correlation with bronchoalveolar lavage fluid.CD+/CD8+ ratio (p less than 0.05). The Bull's eye analysis was considered useful for the quantitative evaluation of regional pulmonary blood flow in pulmonary sarcoidosis, and it was suggested that the mechanism of reduction in perfusion might be resulted mainly in its alveolitis and angiitis. Ventilation abnormality, which may happen prior to reduction in perfusion, may be an important factor of reduction in perfusion. PMID- 1753543 TI - [Pulmonary hemodynamics and home oxygen therapy in patients with chronic respiratory failure]. AB - The authors examined pulmonary hemodynamics with respect to underlying diseases, severity and type of chronic respiratory failure, and the incidence and effect of home oxygen therapy (HOT) in 155 patients with chronic lung diseases (old pulmonary tuberculosis (OTB) 45, chronic pulmonary emphysema (CPE) 54, chronic bronchitis (CBR) 42 and fibrosing lung disease (FLD) 14). They underwent right heart catheterization during a stable period, while breathing room air. The arterial PO2 ranged from 64.3 +/- 9.7 Torr (CBR) to 69.9 +/- 10.0 Torr (CPE), and the mean pulmonary arterial pressure ranged from 17.3 +/- 4.6 mmHg (CPE) to 20.6 +/- 5.4 mmHg (OTB). The incidence of pulmonary hypertension (PH, PA mean greater than or equal to 20 mmHg) was 53.3% in OTB, 40% in CBR, 35.7% in FLD, 23.8% in CPE, 69% in respiratory failure, 40% in quasi-respiratory failure, and 2.1% in non-respiratory failure. The percentage of patients who received HOT was 84.5% in respiratory failure and 54.1% in quasi-respiratory failure. Comparing Type I with Type II chronic respiratory failure, the incidence of PH was lower in the former than the latter (38.3% vs 80.6%), whereas HOT was applied to an equal percentage of patients (67.4%) in both groups. The effect of HOT was evaluated in 11 patients with chronic respiratory failure. The mean pulmonary arterial pressure was 22.7 +/- 4.7 mmHg before HOT, and decreased to 20.7 +/- 5.6 mmHg after 24.5 +/- 10.1 months of HOT. Although this difference was not significant statistically, this result suggests the desirable effect of HOT on pulmonary hemodynamics. PMID- 1753544 TI - [The defensive role of human pulmonary alveolar macrophages and polymorphonuclear leukocytes against a strongly or weakly virulent strains of Cryptococcus neoformans]. AB - The phagocytic and killing activities of human pulmonary alveolar macrophages (PAM) and polymorphonuclear leukocytes (PMN), and superoxide (O2-) production in phagocytizing PAM and PMN were studied by using a strongly and weakly virulent strains of Cryptococcus neoformans (C. neoformans) in mice. The strongly virulent strain was encapsulated with a thick capsule while the other had a thin one. The phagocytic and killing activities of PAM and PMN against the strongly virulent strain were lower than against the weakly virulent one. There was no significant difference between PAM and PMN in terms of phagocytic or killing activities and O2- production. It seems likely that O2- plays no defensive role in the intracellular killing of C. neoformans by PAM and PMN because no correlation was found between the killing activity and O2- production. These results indicate that human PAM and PMN play an effective role in host defense against the weakly virulent strain of C. neoformans encapsulated with a thin capsule but are not effective against the strongly virulent strain encapsulated with a thick capsule. PMID- 1753545 TI - [A case of broncho-bronchiolitis obliterans associated with rheumatoid arthritis and Sjogren's syndrome]. AB - A 45-year-old female patient with rheumatoid arthritis and Sjogren's syndrome was admitted because of progressive exertional dyspnea and palpitation. The chest X ray film was normal except for slight overinflation. Pulmonary function tests indicated severe mixed-type impairment, and arterial blood gas analysis revealed hypoxemia. 99mTc-MAA lung perfusion scintigraphy and 81mKr lung ventilation scintigraphy showed multiple nonsegmental defects in both lungs. During six months of observation, the perfusion defect increased in size and intensity, although the chest radiography remained unchanged. The diagnosis of bronchobronchiolitis obliterans (BBO) was confirmed by open lung biopsy. Glucocorticoid therapy was ineffective, and she died of respiratory failure a month after discharge. It is noteworthy that perfusion scintigram demonstrated the progression of the disease much better than chest radiography, which showed no apparent change during the observation period. PMID- 1753546 TI - [A case report of spontaneous pneumothorax in Marfan's syndrome and an immunohistochemical study of type I collagen in lung tissue]. AB - A 19-year-old male was admitted to Teikyo University Hospital because of dyspnea. The chest film revealed pneumothorax of the right side. The patient was tall and thin, with long tapered extremities. The lens showed ectopia lentis. Echography of the heart showed dilatation of the aorta. A diagnosis of Marfan's syndrome was established on the basis of characteristic skeletal, ocular and cardiovascular findings. At thoracotomy, several bullae were removed by wedge resection. Collagen type distribution in the lung was investigated by an indirect immunohistochemical study using type-special antibody of type I collagen. There were no significant differences in collagen type I in the lung between Marfan's syndrome and control. This suggests that type I collagen in Marfan's syndrome cannot be distinguished from normal collagen I by indirect immunochemical study. PMID- 1753547 TI - [Diffuse panbronchiolitis in two brothers with different clinical courses]. AB - Diffuse panbronchiolitis in two brothers is reported. The elder brother aged 46, was admitted in May 1983 due to severe dyspnea and productive cough, which had gradually worsened over several years. He had severe hypoxemia and hypercapnia. He died at age 47 of respiratory failure due to pseudomonas infection despite antibiotic therapy. The younger brother, at age 41, was admitted in March 1983 due to fever, productive cough, and abnormal shadows on chest X-ray films. He showed mild hypoxemia and his symptoms improved with antibiotic treatment. Since then he has been followed as an outpatient for over 7 years while taking 400 mg of Erythromycin per day, and he has had no exacerbation. These two cases had different clinical courses despite the facts that both had similar conditions of chronic sinusitis and appeared to be exposed to no special environmental or occupational hazards. These facts suggest that not only intrinsic factors, such as defenselessness of airways, but extrinsic factors such as viral, mycoplasmal, or bacterial infection may act together on the mechanisms of the onset and progression of diffuse panbronchiolitis. PMID- 1753548 TI - [A case of follicular bronchiolitis with broncho-pleural fistula in rheumatoid arthritis]. AB - A 67-year-old male diagnosed clinically as having rheumatoid pleuritis and bronchiolitis was treated with adrenocorticosteroid. His clinical findings improved, but following the tapering of the steroid dose, exacerbation occurred. After the steroid dose was increased, serological findings improved, but chest X ray findings revealed no improvement. To re-evaluate the etiology of the bronchiolar lesion, open lung biopsy was performed. The biopsy specimen showed lymphocytic infiltration and formation of lymphoid follicles in and around the bronchioles. The pulmonary lesion was diagnosed as follicular bronchiolitis. PMID- 1753549 TI - [Insidious hearing loss and facial palsy as the presenting symptoms of meningeal carcinomatosis resulting from adenocarcinoma of the lung]. AB - An 80-year-old man was admitted to our hospital with a complaint of insidious hearing loss and facial palsy. Chest X-ray film showed an abnormal shadow in the right lower lobe. Adenocarcinoma of the lung was diagnosed by transbronchial brushing cytology. During admission, headache and dysphagia appeared, although no abnormality was detected in the brain CT and MRI. Lumbar puncture yielded adenocarcinoma cells in the cerebrospinal fluid. A diagnosis of leptomeningeal metastasis from the adenocarcinoma of the lung was considered and intrathecal administration of methotrexate was performed. The patient's condition deteriorated gradually and he died of respiratory failure. Autopsy revealed massive invasion of tumor cells in the leptomeninges of the brain and spinal cord. This case illustrates that facial nerve palsy with insidious hearing impairment may appear as the initial symptoms in meningeal carcinomatosis resulting from lung cancer metastasis. PMID- 1753550 TI - [Flow chart of the diagnosis and treatment of a case of catamenial pneumothorax]. AB - A 44-year-old female had sudden cough during menstruation. She visited a clinic and mild right pneumothorax was pointed out on chest X-ray. She was admitted to our hospital for continuous pneumothorax and tube drainage was performed. Although pneumothorax improved within a week after drainage, catamenial pneumothorax was suspected because her serum CA 125 showed a high value of 109 U/ml. Therefore diagnostic pneumoperitoneum was performed during the next menstruation, and right pneumothorax occurred. Laparoscopy revealed pelvic endometriosis and thoracoscopy revealed a few small holes in the right diaphragm. The case was diagnosed as catamenial pneumothorax and hormonal treatment was given. She had been well for one year without recurrence of pneumothorax. The authors made a flow chart for diagnosis and treatment based on this case and discussed its value in relation to cases described in the literature. PMID- 1753551 TI - [A case of metastatic rib tumor from thyroid cancer confirmed by the presence of thyroglobulin]. AB - A 63-year-old female, with a chief complaint of right chest pain was referred to our hospital because of an abnormal right chest wall shadow on chest X-ray. A rib tumor was suspected based on her chest CT scan. Percutaneous needle biopsy yielded a diagnosis of well-differentiated adenocarcinoma. As metastatic rib tumor was suspected, the primary tumor was sought for. A thyroid gland nodule was recognized by ultrasonography, and the cytological diagnosis was class V. Immunohistological demonstration of the thyroglobulin studies of the rib tumor tissue revealed papillary and trabecular patterns of cell arrangement and the presence of thyroglobulin existence. Definitive diagnosis of metastatic rib tumor from thyroid cancer was established. Immunohistological examination is useful to confirm the diagnosis of metastatic cancer of thyroid origin. PMID- 1753552 TI - Research on alcohol metabolism: a historical perspective. AB - The primary enzymatic steps in ethanol metabolism to acetaldehyde, acetate and CO2 + water have been known for many decades, but only a few clinical implications were recognized, such as the risk of malnutrition due to use of alcohol as a source of calories, and the use of disulfiram and other ALDH blockers in the treatment of alcoholism. In the last four decades, however, further understanding of alcohol metabolism has led to recognition of the changes secondary to altered NAD:NADH ratio; to ethanol oxidation by, and induction of, the microsomal cytochrome P450IIE1 system; to fatty acid ethyl ester formation; to the increase in hepatic O2 consumption; and to the formation of acetaldehyde protein adducts and antibodies to these. This new knowledge has led to important progress in relation to the pathogenesis and treatment of alcoholic liver disease, and to potentially valuable new diagnostic procedures for detecting heavy drinking and incipient alcoholic tissue damage. These advances demonstrate strikingly how basic research into fundamental biological processes can yield important and unanticipated practical benefits. PMID- 1753553 TI - Bile acids and biliary carcinoma in pancreaticobiliary maljunction. AB - Pancreaticobiliary maljunction is frequently associated with biliary carcinoma, whether or not there is choledochal dilatation. In this anomalous condition, pancreatic juice regurgitates and the mixture of bile and pancreatic juice stagnates in the biliary tree. In cystic choledochal dilatation, cancers arise, mainly in the dilated bile ducts, while in patients not having cystic dilatation, tumors arise in the gallbladder. Gallbladder bile and/or bile duct bile from fifteen cases of pancreaticobiliary maljunction, including five cancer patients, was analysed biochemically and compared with control bile from 6 patients with a normal pancreaticobiliary junction. Bile levels of pancreatic enzymes were extremely high in the anomalous junction group. In the bile duct bile from patients with cystic choledochal dilatation with pancreaticobiliary maljunction, the concentrations of deoxycholic acid (DCA), lithocholic acid (LCA) and unconjugated bile acid fractions were increased regardless of the presence of cancer. Increases of these bile acid fractions, which are known to have a cancer promoting effect, were also seen in gallbladder bile from the cancer patients without cystic dilatation. PMID- 1753554 TI - Appraisal of adjuvant chemoendocrine therapy with tamoxifen plus tegafur in patients with breast cancer. AB - To assess chemoendocrine therapy in the adjuvant treatment of patients with Stage II or III breast cancer, 228 patients were enrolled in a 12-month trial period from January 1982 to January 1983. One hundred ninety evaluable patients were followed up for five years. The regimen in this trial consisted of intravenous administration of 13 mg of mitomycin C per m2 during the operation and 6.5 mg of the same drug per m2 on the first day, and oral administration of 600 mg of tegafur per m2 alone or supplemented with 13 mg of tamoxifen per m2 for two years. No survival advantage was observed with addition of tamoxifen to tegafur in terms of five-year survival (88.7% vs 86.6% for Stage II and 69.9% vs 82.2% for Stage III). However, there was a significant prolongation of relapse-free survival among patients receiving tegafur and tamoxifen as compared with those who received tegafur alone: 72.9% vs 55.8% (p = 0.098 in the logrank test). PMID- 1753555 TI - Coping style of schizophrenic patients in the recovery from acute psychotic state: a preliminary study. AB - This study was undertaken to clarify a clinically effective coping style of 13 schizophrenic patients during recovery from an acute psychotic state. Sixteen recovered depressives served as the control group. A comparison of the coping behavior profile between the two groups revealed that changes in physical activity were significantly more frequent in the schizophrenics (62%) than in the depressives (25%). PMID- 1753556 TI - Augmentation of anti-tumor effect of interleukin 2 with sizofiran in mice. AB - Augmentation of anti-tumor effect of interleukin 2 (IL-2) with sizofiran (SPG) was demonstrated with in vivo and in vitro experiments. C3H/He mice with subcutaneously inoculated X5563 tumor were used as experimental models. IL-2 at a dose of 2 X 10(4) units per mouse by subcutaneous injection, and/or SPG at a dose of 0.1 g per mouse by intramuscular injection were given every other day for a total of ten times. Tumor infiltrating lymphocytes (TIL) were investigated with the avidin-biotin peroxidase complex method. Cytotoxic activity of mice spleen cells after the therapies against YAC-1, X5563 and MH134 were tested with 51Cr release assay. IL-2 or SPG alone suppressed tumor growth in vivo, although not significantly. Combination therapy with IL-2 and SPG suppressed tumor growth in vivo significantly (p = 0.04). Mice treated with the combination survived longer than the mice treated with the single drug (p less than 0.05) and the controls (p less than 0.001). Immunohistologically, more TILs were seen in the combination group than the other groups. In the cytotoxicity study, 3 days after initiation of the therapies, augmentation of natural killer (NK) activity was greater by the combination than by IL-2 or SPG alone. After incubation with IL-2, the spleen cells from mice treated with the combination showed higher cytotoxicity against X5563 or MH134 tumors than those treated with the single drug or controls. Obtained results suggested that combination therapy with IL-2 and SPG effectively induced NK cells and lymphokine-activated killer cells in vivo and may lead to greater clinical benefit in the treatment of malignancies. PMID- 1753557 TI - Vascular compression of the eighth cranial nerve as a cause of vertigo. AB - Some patients have vertigo that is more or less constant, associated with varying degrees of nausea, and only relieved by bedrest. This disorder, named disabling positional vertigo (DPV), was found to be caused by a blood vessel or vessels compressing the eighth cranial nerve in its intracranial portion, and it can be relieved by microvascular decompression (MVD) of the nerve. Important in the differential diagnosis of DPV are a detailed history, the results of audiometry (10 to 15 dB interaural threshold difference or a small mid-frequency notch), acoustic middle ear reflex response testing (may be abnormal), and recordings of brainstem auditory evoked potentials (BAEP). BAEP in such cases show increased conduction time in the auditory nerve and/or prolonged latency of wave V recorded from the contralateral ear, possibly the result of brainstem compression. Abnormalities on vestibular testing often do not reflect the severity of the illness. Forty-one patients who underwent MVD to treat DPV in one year at the author's institution have been followed for 4.5 to 5.5 years. By self-evaluation, 20 had excellent and 10 good results of the operation. The success of this procedure is even higher today, since it was found that very small blood vessels, including veins, can cause DPV; thus all vessels touching the nerve are now managed. Complications of MVD are rare. The most frequent, hearing loss, occurred in only one patient in this series. PMID- 1753558 TI - Neuromonitoring in operations in the skull base. AB - Methods to monitor the integrity of cranial motor nerves during operations on skull base tumors have been developed over the past decade. These methods can help the surgeon to identify cranial motor nerves that are located in the surgical field but which may not be visible directly. Methods have also been developed that allow monitoring of the function of sensory systems such as the auditory system and it has been shown that brainstem auditory evoked potentials can provide important information about the integrity of the auditory nervous system. It has been shown in several studies that such neuromonitoring, when performed during operations in the skull base, can help reduce the incidence of permanent neurological deficits that may occur with the removal of large tumors. We have also shown that such monitoring can be performed routinely without interfering noticeably with the actual surgical procedures. PMID- 1753559 TI - A 59-year-old man with an abnormal shadow in the right lung. PMID- 1753560 TI - [QT interval and the autonomic nervous system in coronary disease and sick sinus syndrome]. AB - The autonomous nervous system influence on sinus node (SN) in both physiological and pathological states is the most important factor determining its function. There are only few publications about autonomous nervous system action on electrophysiological properties of the human heart (ventricles), specially in patients with different types of sick sinus syndrome (SSS). Electrocardiograms of 113 patients (pts) with coronary heart disease, suspected for SSS, recorded during transesophageal atrial pacing before and after pharmacological denervation of the heart, were analysed. For heart denervation propranolol (0.2 mg/kg body weights) and atropine (0.04 mg/kg body weights) intravenously were used. We analysed sinus cycle length (P-P), QT interval and QTc (QT interval corrected according to Bazett's formula) during both sinus and paced rhythm (100 bpm), before and after denervation of the heart. During clinical observations (including Holter monitoring) and after electrophysiological testing we excluded SSS in 28 pts (group A) and confirmed diagnosis of SSS in 85 pts (group B). Group B was divided in two parts; pts with normal (group B1) and abnormal (group B2) intrinsic properties of the SN. Group B1 included 23 pts (15 men and 8 woman from 36 to 74, mean 53 +/- 9) with normal sinus cycle length after denervation (according to Joses's formula) and maximal, corrected sinus node recovery time after denervation less than 422 ms. Group B2 included remaining 62 pts (26 men and 36 woman from 36 to 80, mean 59 +/- 9). In groups A and B1 denervation of the heart shortens P--P, QT, QT100 and QTc100 significantly. Only QTc in A and B1 and all parameters in group B2 didn't change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753561 TI - [Spectrum analysis of heart rate. A method of studying the role of the autonomic nervous system in the regulation of blood circulation]. AB - Spectral analysis of heart rate variability has recently been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular automatic regulatory responses. In 12 ambulant normotensive healthy young males (mean age 23 +/- 1 years) after a period of 10 min. for stabilisation, a continuous ecg recording (lead CM-5) for 8 min. was obtained in the supine and standing position, with a controlled respiration rate 15/min. Power spectrum of 512 point time series (R-R intervals) in both positions was calculated using a fast Fourier transform-based window periodogram method. Based upon results from the literature the power spectrum analysis was performed on two components: low frequency LF (0.05-0.15 Hz) and high frequency HF (0.15-0.50 Hz). Mean R-R interval decreased on standing position from 0.79 +/- 0.10 s to 0.59 +/- 0.11 s (p less than 0.001). The ratio HF/LF in supine was 0.63 +/- 0.70 and on standing position 2.54 +/- 0.73 (p less than 0.001). The relative LF component of the total HR power spectrum increased from 22.8% +/- 12.1% to 42.9 +/- 14.4% (p less than 0.001) after changing the position from supine to standing, and the relative HF component decreased from 56.3 +/- 22.4% to 25.5 +/- 16.2 (p less than 0.001). The total power was significantly lower when standing in comparison to supine position (681 +/- 519 s2, 1188 +/- 963 s2 respectively, p less than 0.05). Our results suggest that heart rate fluctuations in supine position in normal men are mainly vagally determined (HF power spectrum component).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753562 TI - [Electric cardioversion after surgical correction of the mitral valve defect. Prognostic value of the two-dimensional and Doppler echocardiography in the assessment of its long-term effectiveness]. AB - In 82 patients after mitral valve surgery (59--commissurotomy, 23--valve replacement--Bjork-Shiley or St. Jude prosthetic valve), 2-D and Doppler echocardiography were performed one day before electrical cardioversion. Regular sinus rhythm was maintained to 180 days in 28 patients (34%), over 180 days in 54 patients (66%). The statistical differences (p less than 0.05) between the following echocardiography parameters of these two groups were determined: parasternal long axis view: aortic, atrial, right and left ventricular dimensions (not significant--NS); apical four-chamber view: left and right atrial, left and right ventricular areas--NS; apical two-chamber view: left atrial area--p less than 0.05; pulmonary valve: peak flow velocity--NS, acceleration time--NS; mitral valve: effective area--p less than 0.05, pressure half-time--p less than 0.05, mean gradient--NS, mean flow--NS, E-wave max. flow velocity--NS. These data suggest, that left atrial area less than 30 cm2 derived from two-chamber view and Doppler effective mitral area more or equal 2, 10 cm2 may be important and good predictors of long-term results of cardioversion in patients after mitral valve surgery. PMID- 1753563 TI - [Measurement of arterial blood pressure using the sphygmomanometer-S and the direct method]. AB - Sphygmomanometer--S is the microcomputer device measuring blood pressure (BP) by the noninvasive sphygmooscillographic method following standard algorithm. When compared sphygmomanometer--S with auscultatory method, this device overestimated systolic BP by 7 mm Hg, and underestimated diastolic BP by 9 mm Hg on the average. In other words, sphygmomanometer--S overestimated systolic pressure and lowers diastolic pressure in relation to auscultatory method in the same ratio and value, as the direct method in relation to the auscultatory method. In this study, we evaluated the accuracy of the results obtained by sphygmomanometer--S, with simultaneously recorded radial artery pressure by direct method. In 15 patients 27-60 years of age undergoing cardiac surgery BP was measured by sphygmomanometer--S and direct method simultaneously on the same left upper extremity. We measured direct radial artery pressure using AE 840 Nycotron transducer and Philips amplifier. BP by sphygmomanometer--S was obtained on the same left arm using cuffs of size 11 x 24 cm and 13 x 35 cm. In 15 patients 124 pairs of BP measurement were carried out with sphygmomanometer--S and direct method. The regression equation for systolic, diastolic and mean pressure demonstrated the coincidence of the BP results obtained by sphygmomanometer--S with direct method. The correlation coefficient (r) was 0.97 for systolic, 0.90 for diastolic and 0.92 for mean pressure. Systolic and diastolic pressure measured by the sphygmomanometer--S were 2 mm Hg and mean 0.6 mm Hg higher on the average, than the same pressures obtained by direct method (ryc. 1). These differences were statistically not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753564 TI - [Cardiac manifestations of tumor recurrence in the right lung]. PMID- 1753565 TI - [Indications for emergency surgical treatment of ectopic atrial tachycardia]. AB - Recurrent automatic atrial tachycardia can induce dilated cardiomyopathy. We present clinical and therapeutic problems of 16 years old male with ectopic left atrial tachycardia refractory to pharmacological therapy. In this patient long periods of atrial tachycardia 200-240/min due to lack of effective medication caused cardiac failure. Uncontrolled taking of various antiarrhythmic drugs and persistent tachycardia led to cardiogenic shock. The electrophysiologic study revealed focus of the tachycardia localized in the area of left cardiac auricle. The rate of the tachycardia was changing from 84 to 240/min, with periods of Mobitz I block in the AV node. In periods of 1:1 AV conduction the tachycardia had sometimes LBBB QRS morphology. The atrial tachycardia provoked unsustained ventricular one. The patient was operated. Resection of left auricle and mitral valvuloplasty were performed. After the operation the patient regained undisturbed sinus rhythm and symptoms of heart failure disappeared. PMID- 1753566 TI - [Obesity and ischemic heart disease]. PMID- 1753567 TI - [Blood platelets and ischemic heart disease and myocardial infarction]. PMID- 1753568 TI - [Electric ablation and intracardiac cardioversion in the treatment of atrial arrhythmias]. PMID- 1753569 TI - [Comparison of the clinical and hemodynamic effects of nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate in acute myocardial infarction]. AB - One hundred and eighty patients with acute myocardial infarction (MI) were followed up. The patients were divided into 3 groups: (1) those receiving glyceryl trinitrate (GTN) (n = 43); (2) those on isosorbide dinitrate (ISDN) (n = 66); (3) those on isosorbide-5-mononitrate (IS-5-MN) (n = 71). In all the groups, the drugs were given by long-term continuous oligovolumic infusion. Following 24 hours of administration, 66.7, 47.3, and 17.1% increases in infusion rates were required in 74.4, 72.7, and 26.8% of the patients from Groups 1, 2, and 3, respectively. All the agents produced a pronounced antianginal effect and resulted in alleviated acute left ventricular failure. The in-hospital mortality rates were 16.2, 16.7, and 12.7% in Groups 1, 2, and 3, respectively. GTN, ISDN, and IS-5-MN caused adverse effects in 4.7, 18.2, and 2.8% of the patients from Groups 1, 2, and 3, respectively. PMID- 1753570 TI - [Effect of diltiazem on silent myocardial ischemia]. AB - Thirty-four patients with coronary heart disease who had silent myocardiac ischemic episodes as evidenced by long-term ECG monitoring were examined. Silent ST-segment elevations and depressions were encountered 2.7- and 4.9-fold as compared to manifest ones. The fact that the CHD patients had silent ST-segment depressions and/or prolonged high-amplitude silent ST-segment elevations suggests a grave severity of abnormal myocardial processes. There was a reduction in the number, duration of silent ST-segment elevations and depression episodes and in the amplitude of silent ST-segment depressions. This may indirectly indicate that the agent affects predominantly coronary blood flow and coronary vascular tone. PMID- 1753571 TI - [Long-acting nitrate-induced changes in microcirculation and tissue oxygen balance in patients with coronary heart disease]. AB - A total of 56 patients with Functional Class II angina pectoris and 25 healthy subjects were examined. Long-acting nitrates were ascertained to result in profound venular dilatation, slight arteriolar dilatation, moderately decreased erythrocyte aggregation and improvement of tissue oxygen supply. The most marked increase in exercise tolerance and reduction in the frequency of anginal attacks were noted in patients with normal and narrowed venules. There were no significant changes in microcirculation and exercise tolerance in patients with baseline dilated venules. It is concluded that the microvasculature may be one of the criteria for applying long-acting nitrates in patients with coronary heart disease on an individual basis. PMID- 1753572 TI - [Use of bepridil in patients with angina pectoris]. AB - The efficacy of the calcium antagonist bepridil given in a dose of 200-400 mg/day was evaluated in 22 patients with Functional Classes II-III stable angina pectoris. In addition to clinical assessments, repeated bicycle ergometric exercise tests were performed in the patients. The agent was found to be highly potent, well tolerated, and to cause no grave adverse effects. PMID- 1753573 TI - [Role of hemorheologic and hemodynamic factors for the efficacy of therapeutic plasmapheresis in patients with ischemic heart disease]. AB - Changes in blood rheological properties and central hemodynamic parameters were studied in patients with Functional Classes III-IV angina pectoris who had undergone therapeutical plasmapheresis. Drastic baseline changes in blood rheological properties, a reduction in myocardial contractility, and high total peripheral vascular resistance (hypokinetic circulation) were found to be indications for plasmapheresis supplemented to antianginal therapy. A positive clinical effect of this therapeutical method may be, to a definite extent, predicted in these patients. The first plasmapheresis procedure improved blood rheology due to the plasma component, making the high baseline levels of fibrinogen and total protein normal, lowered increased platelet aggregation, repeated procedures enhanced the electric superficial charge of red blood cells and the stroke index of the left ventricle. PMID- 1753574 TI - [Microcirculatory effects of hemosorption in patients with stable angina pectoris, based on data from radionuclide imaging]. AB - The impact of hemosorption on microhemo- and lymphocirculation, reserve microcirculatory bed potentials, and capillary permeability was examined by using radionuclide techniques in 46 patients with coronary heart disease refractory to drug antianginal therapy. Hemosorption was found to yield a beneficial clinical effect in 47.8% of the patients, resulting in a substantial increase in microcirculation and its reserves and a decrease in microvascular resistance both at rest and in reactive postischemic hyperemia. But it deteriorated the microcirculation in patients refractory to it. PMID- 1753575 TI - [Predicting the efficacy of rehabilitation in patients with prior myocardial infarction]. AB - The results of a 2-year follow-up of 400 patients with prior myocardial infarction (MI) and bicycle ergometric findings of intracardiac hemodynamic parameters and oxygen supply during exercise tests, and the criteria for tetrachoric index significance within the confidence intervals were used to reveal the factors predicting the efficacy of rehabilitative treatment. To predict decreased working capacity in the long-term period is determined by the extent of lesion after myocardial reinfarction, while angina pectoris and arterial hypertension are of significance in patients without reinfarction. A role of dynamic indices was defined in predicting decreased working capacity. Further lowered working capacity may be judged from the changes occurring in threshold exercise capacity and left ventricular end-diastolic volume in the first 6 months of postinfarction. PMID- 1753576 TI - [The efficacy of isometric training during hospitalized rehabilitation in patients with myocardial infarction]. AB - The study included 57 patients with myocardial infarction who underwent isometric exercise tests on days 10 and 30 of hospitalization. The patients of the main group had isometric exercise tests by using a key expander for 20 days between the first and second exercise tests. The tests were performed in 4 stages, each lasting 5 days. The patients from the control group had no tests. The study had indicated that isometric exercise tests performed in the hospital treatment period enhance the patients' tolerance to static exercise and they are sufficiently effective despite its short duration. PMID- 1753577 TI - [Effect of hyperbaric oxygenation on the incidence of the antianginal agent withdrawal syndrome in patients with angina pectoris]. PMID- 1753578 TI - [Plasma apolipoproteins B and AI in healthy individuals and patients with coronary atherosclerosis in a male population from Lithuania]. AB - The paper discusses the results from a study into apolipoproteins B (apo-B) and AI (apo-AI) and apoB/apo-AI ratios in the blood of 188 healthy donors and 122 male patients with coronary atherosclerosis. Atherosclerotic lesions were coronary angiographically documented. The study was performed (in two age groups of patients: 1) those under 45 years and 2) those over 45 years. A relationship was examined between the levels of apolipoproteins and the lesion of one, two, three or more coronary arteries in the two age groups. The studies indicate that there are various mechanisms responsible for the pathogenesis of atherosclerosis in the age groups in question. It is concluded that the younger a patient is, the higher probability that elevated blood apo-B levels are essential in the pathogenesis of coronary atherosclerosis is. Determination of plasma apo-B and apo-AI levels and apo-B/apo-AI ratios enables a potential number of diseased coronary arteries to be predicted. PMID- 1753579 TI - [Atherogenic properties of sera and low-density lipoproteins in patients with diabetes mellitus]. AB - The effects of sera and low density lipoproteins (LDL) on cholesterol levels were evaluated in cultured aortic intimal cells from patients with Types 1 and 2 diabetes mellitus. About 80% Type 1 diabetic patients' sera and 90% of Type 2 diabetic patients' sera caused a 1.5-4-fold increase in intracellular cholesterol levels. LDL isolated from atherogenic sera induced intracellular cholesterol accumulation. There was a close correlation between the atherogenic effect of the sera and LDL. The atherogenic properties of the sera and LDL from patients with diabetes mellitus were unassociated with the examinees' age. There was a relationship between the atherogenic serum effect and the compensation of carbohydrate metabolism in male patients with Type 1 diabetes mellitus. The atherogenic effect of the sera and LDL failed to increase in patients with Types 1 and 2 diabetes mellitus concurrent with coronary heart disease. The property of the sera to accumulate intracellular cholesterol is likely to be typical of diabetes mellitus and mainly due to disturbed LDL metabolism. PMID- 1753580 TI - [Changes of blood antioxidative enzyme activity and lipid levels in patients with coronary atherosclerosis treated with probucol]. AB - The paper provides the results of 3-month probucol (lipomal) treatment of patients with coronary heart disease concurrent with Types 2a and 2b hyperlipidemia. There were 20% and 17% decreases in total cholesterol and low density lipoprotein cholesterol levels, respectively. The drug failed to affect the levels of high density lipoprotein cholesterol and triglycerides. Having antioxidative properties, probucol significantly enhances the activity of the antioxidative enzymes superoxide dismutase and glutathione peroxidase, which controls the efficacy of coronary heart disease patients with hyperlipidemia. PMID- 1753581 TI - [Seasonal variations of the lipid spectrum in patients with post-infarction cardiosclerosis and arterial hypertension]. AB - The lipid spectrum was examined in 77 Moscow male residents aged 30-60 years in winter and in summer. The examinees were divided into 4 groups: (1) healthy subjects; (2) patients with arterial hypertension; (3) those with post-infarction cardiosclerosis; (4) those with the two abnormalities. The levels of total cholesterol, triglycerides, high density lipoprotein cholesterol, low and very low density lipoprotein cholesterol, and circulating immune complex cholesterol were measured. All the groups were demonstrated to have lower cholesterol and low density lipoprotein levels in summer than in winter, which should be taken into account in the diagnosis and treatment of atherosclerosis-associated diseases. PMID- 1753582 TI - [Responses of the pressor and depressor regulatory systems to high sodium intake in borderline arterial hypertension]. AB - A total of 25 healthy individuals and 48 borderline hypertensives aged 22-56 years were examined. The healthy subjects having a salt load showed elevated blood histamine concentrations and an unchanged vascular response to histamine, and reduced plasma renin activity. The patients having a salt load displayed high histamine levels, sharply decreased vascular response to histamine, and undepressed plasma renin activity. It is concluded that the pressor mechanisms responsible for controlling vascular tone are more active than the depressor ones during the salt load in patients with borderline hypertension. The humoral response of the patients to a salt load was impaired with elevated plasma cortisol concentrations, which was not followed by sodium retention in the body. PMID- 1753583 TI - [Perspectives of studying the functional pathology of the heart]. PMID- 1753584 TI - [Clinical and hemostatic evaluation of curantyl in hypertensives]. AB - Curantyl supplemented to the multimodality therapy for patients with Stage II essential hypertension with uncomplicated events or complicated by hypertensive crisis was ascertained to lower the intensity of intravascular blood microcoagulation due to its modifying effect on the procoagulative and thrombocytic links of hemostasis and blood fibrinolytic activity. The drug exerted no marked positive action on clinical manifestations of the disease and caused no significant changes in the parameters of hemostatic procoagulative and thrombocytic links and blood fibrinolytic activity. PMID- 1753585 TI - [Cardiolipin antibodies in non-specific aortic arteritis]. AB - Cardiolipin antibodies are detected in the sera from patients having a wide range of clinical manifestations, including venous and arterial thrombosis, obstetric abnormality, damaged CHS and diseased vascular wall. To clarify the clinical value of cardiolipin antibodies, 21 patients with non-specific aortic arteritis were studied. The antibodies were determined by enzyme immunoassay. Their higher levels were found in 5 (24%) patients. The patients who were positive for cardiolipin antibodies showed a significant increase in the incidence of occlusive lesions (p less than 0.001) and a moderate increase in that of valvular heart diseases. The findings suggest that cardiolipin antibodies might contribute to the pathogenesis of non-specific of aortic arteritis. PMID- 1753586 TI - [Effect of manual therapy on blood pressure in hypertensives with cervical osteochondrosis]. AB - The efficacy of drug (inderal, corinfar) treatment in combination with manual therapy (the course was 4-7 sessions) was examined in hypertensives with cervical osteochondrosis. The latter was evidenced by X-ray studies. Clinically, cervical osteochondrosis appeared as vertebrobasilar insufficiency. The vertebral artery bed displayed circulatory disorders documented by rheoencephalography, electroencephalography, ultrasound Doppler echography of the head and neck vessels. Treating the patients with drugs in combination with manual therapy resulted in improved circulation in the vertebral artery bed, lower clinical signs of vertebrobasilar insufficiency. There was a more persistent and more pronounced decrease in blood pressure with small-dose antihypertensive agents. PMID- 1753587 TI - [Differential diagnosis, prevention and therapy of vascular disorders in miners]. PMID- 1753588 TI - [Classification of ventricular septal defects]. AB - The hearts were examined from 125 patients with isolated ventricular septal defects (VSD) who had died at the age of 0-14 years before or without operation. One hundred twenty five heart showed 178 defects: 103 with isolated, 22 with multiple VSD. Five major defect types were identified: (1) perimembranous; (2) sinus; (3) central trabecular; (4) boundary muscular trabecular; (5) infundibular. According to the relevance of fibrous skeleton and cardiac conduction system, the defects of various sites are divided into 2 large groups: 1) unadjacent to them (muscular) and 2) adjacent. In terms of septal geometry, there are also two large groups: 1) those located in the inflow portion of the septum and 2) those located in the outflow portion. PMID- 1753589 TI - [Effect of hemodynamic factors on the development of digoxin resistance in patients with aortic diseases complicated by congestive heart failure]. PMID- 1753590 TI - [Examination of peripheral blood flow in healthy subjects using laser Doppler flowmetry]. PMID- 1753591 TI - [Adaptive stabilization of myocardium under the influence of electroacupuncture and cardiac protection]. AB - Adaptation of animals to short-term stress is known to result in the development of the adaptive structure stabilization phenomenon. At the level of the heart, the phenomenon appears as increased resistance to elevated catecholamine and calcium levels, reperfusion paradox. This study attempted to reproduce the phenomenon without applying any stress, but using a course of transauricular electric acupuncture. The isolated hearts of rats undergoing a course of the acupuncture were ascertained to show a clear-cut high resistance to the reperfusion paradox. After coronary ligation, the extent of necrosis in the animals having the acupuncture was significantly lower, as in those adapted to stress. The assumption that the phenomenon forming the basis for cardioprotective effects develops with electric acupuncture is discussed in the paper. PMID- 1753592 TI - [Calcium binding to the erythrocyte cytoskeleton in spontaneously hypertensive rats]. AB - The paper outlines a new La(3+)-induced mechanism of Ca2+ binding to rat red blood cells. Other compounds elevating intracellular Ca2+ concentrations, such as A-23187, ionomycin, and orthovanadate, and some activators of phosphotransferases (TPA, dibutyryl cAMP) fail to initiate the binding. Inhibitors of calmodulin dependent processes, such as calmidazolium and trifluoroperazine, diminish La dependent Ca2+ binding. La(3+)-induced Ca2+ binding is followed by an increased cytoskeleton incorporation rate of 14C metabolites of glucose. The rate of Ca2+ binding and 14C metabolite incorporation was 30% and 80% higher, respectively, but Ca+ binding capacity was increased by 45% in SHR as compared to WKY rats. Due to the fact that La3+ enhances the phosphorylation of proteins with molecular masses of 14, 36, and 58 kD, it is suggested that Ca2+ binding alterations should be determined by changes in phosphorylation and glucose metabolic disturbances in spontaneously hypertensive rats. PMID- 1753593 TI - [Evaluating the protective effect of polyhydroxy-1,4-naphthoquinones in a model of experimental myocardial occlusion-reperfusion]. PMID- 1753594 TI - [Pro-arrhythmic effects of anti-arrhythmic preparations]. PMID- 1753595 TI - [Specific features of the condition and study of the cardiovascular system in patients with excessive body mass]. PMID- 1753596 TI - [Why to ban circadian chronotherapy?]. PMID- 1753597 TI - [Possibilities of chronopharmacology]. PMID- 1753598 TI - [The ability of captopril to enhance the anti-anginal effect of isosorbide dinitrate in patients with stable exercise-induced angina pectoris]. AB - The interaction between isosorbide dinitrate (ISDN) and the angiotensin converting enzyme inhibitor captopril was investigated in 14 patients with coronary heart disease concurrent with stable exercise-induced angina pectoris. The efficacy of placebo, ISDN, 10 mg, captopril, 50-100 mg, and ISDN + captopril was evaluated in each patient by pharmacodynamic treadmill studies. The single blind, randomized technique was applied. Captopril alone produced a weak antianginal effect. The concomitant use of ISDN and captopril showed significantly more marked and prolonged effects than ISDN alone. The highest effect was exhibited by ISDN supplemented with captopril in 6 patients who had been refractory to ISDN alone. Thus, captopril may potentiate the antianginal effect of ISDN. PMID- 1753599 TI - [Adequacy of applied mathematical methods in the detection of biorhythms]. PMID- 1753600 TI - [Clinical relevance of hypercholesterolemia and its correction]. PMID- 1753601 TI - [Clinical pharmacology of nisoldipine, a new calcium antagonist]. PMID- 1753602 TI - [Correlation of the early ventricular repolarization syndrome with prolapse of the mitral valve and of the left ventricular accessory chord]. PMID- 1753603 TI - [Changes of the Q-T interval during isometric exercise, induced by anti arrhythmic agents]. PMID- 1753604 TI - [Rare complications of cardiac pacing]. PMID- 1753605 TI - [Oxygen-dependent mechanisms of biocidal activity of neutrophils in patients with dilated cardiomyopathy]. PMID- 1753606 TI - [Relationship between the detection of circulating antibodies to antigen with a molecular weight of 67 kD and the severity of clinical manifestations of infectious-allergic myocarditis]. AB - Infectious allergic myocarditis (IAM) is frequently complicated by signs of congestive heart failure (CHF). IAM patients generally suffer from rhythm and conduction disturbances which can be the leading symptom of the disease in some patients. Slowly progressive immune inflammation in the myocardium makes the differential diagnosis difficult in IAM and dilated cardiomyopathy in which endomyocardial biopsy and cardiospecific immunological examinations of the patient are of great significance. Identification of the autoimmune process in the myocardium and early immunodepressive therapy may arrest the progression of myocardial damage. The purpose of the present study was to examine the relationship between antigen antibodies and clinical manifestations of myocardial damage in IAM. PMID- 1753607 TI - [Diagnostic usefulness of ECG changes in response to exercise in women with various forms of ischemic heart disease]. AB - The results of bicycle ergometry and pharmacological tests with isoproterenol and dipyridamol, 24-hour monitoring and blood levels of endogeneous opioids were studied in 99 females with chest pain who had undergone angiography. Coronary microcirculation was examined in 29 patients by introducing albumin microspheres into the left ventricle. The angiography revealed coronary atherosclerosis in 30 patients, whereas its signs were not found in 8 females with documented coronary heart disease (CHD). The predictive value of positive exercise tests in females with angina pectoris was higher for the diagnosis of CHD, including its types without coronary atherosclerosis. In patients with cardialgias, the predictive values of exercise tests were equally low for the diagnosis of coronary atherosclerosis, vasospastic and microvascular CHD types. The patients with cardialgias caused by autonomic dyshormonal myocardiodystrophy showed low blood beta-endorphin and leu-enkephalin levels. PMID- 1753608 TI - [The value of early exercise testing in patients with myocardial infarction complicated by evolving left ventricular aneurysm]. AB - The values of an early exercise test limited by criteria for test termination were compared with coronaro- and ventriculographic measurements made 2-3 days after the test in 51 males of working age who suffered from transmural myocardial infarction complicated by local aneurysm in 12 cases and by overall left ventricular aneurysm in 39. The exercise test performed in the early periods was found to substantially increased its sensitivity. The isolated ST-dominant segment elevation in patients with local aneurysm and isolated coronary artery lesion indicated that the patients had a favourable prognosis. On the contrary, the combination of two criteria or more of a positive test in patients with global aneurysm and multivessel disease suggests that the patients with temporary disability should be followed up. The presence of T-dominant ST-segment elevation, anginal pain concurrent with an inadequate BP elevation shows that there is a high risk for postinfarction complications. PMID- 1753609 TI - [Diagnostic value of left ventricular diastolic function using pulsed Doppler echocardiography in patients with ischemic heart disease]. AB - Transesophageal atrial pacing was performed in 54 patients (mean age 50.0 +/- 6.8 years) to diagnose coronary heart disease (CHD). ECG was recorded in 12 leads during the test. Echocardiography was used to assess local contractile disorders. The diastolic function of the left ventricle was examined by pulsed Doppler echocardiography in the postpacing period. Thirty eight patients were found to have altered Doppler parameters for transmitral blood flow in the postpacing period as compared to the resting period. Sixteen patients without CHD displayed no changes in the left ventricular diastolic function in the postpacing period. Two types of transmitral blood flow disorders were identified in CHD patients in the postpacing period. The so-called "pseudonormal" type of transmitral blood flow was typical of patients with the most severe contractile impairments and grave course. Abnormalities in local contractility and signs of left ventricular diastolic dysfunction were ascertained to be a sensitive marker for myocardial ischemia. PMID- 1753610 TI - [Correlation of some parameters of carbohydrate metabolism and central hemodynamics in the early stages of circulatory insufficiency in patients with ischemic heart disease]. AB - The study was undertaken to examine central hemodynamic and carbohydrate metabolic parameters in patients with coronary heart disease (with or without signs of chronic heart failure, Stages I and IIA). The changes in carbohydrate metabolism in CHD patients were detected earlier than those in central hemodynamics. In patients with Stage I heart failure, who had normal resting hemodynamic parameters, metabolic parameters were indicative of abnormalities in carbohydrate metabolism: there was a reduction in carbohydrate tolerance and red blood cell release of insulin in response to glucose load and an increase in blood immunoreactive insulin, erythrocytic glucose-6-phosphate dehydrogenase activity and greater adrenalin- and insulin-containing erythrocytes. It is suggested that it is advisable to determine the above parameters of carbohydrate metabolism in patients with coronary heart disease. PMID- 1753611 TI - [Transcutaneous transcatheter use of laser recanalization of coronary arteries in patients with ischemic heart disease]. AB - The paper discusses the potential possibility and effectiveness of X-ray endovascular laser recanalization (ELR) of the coronary arteries in order to treat coronary atherosclerosis in patients with coronary heart disease. The intervention was performed in 4 patients (into the anterior interventricular artery in 3 and into the right coronary artery in 1). In 3 of 4 cases, X-ray ELR proved to be successful, in one case the intervention failed due to technological reasons. Recanalization of a completely occluded segment of the coronary artery with a residual stenosis of no more than 40% was observed in two cases. Laser recanalization of profound local coronary stenosis was made in the mid-third of the vessel in one case. It can be stated that X-ray ELR of the coronary artery may extend the scope of X-ray surgical therapeutical tools of the treatment of coronary atherosclerosis. At the same time, accumulation of clinical experience and further improvement of laser and laser catheter engineering are essential in defining the value and possible scope for the application of this method. PMID- 1753612 TI - [Comparative study of the effect of drug therapy and its combination with hyperbaric oxygenation and hemosorption on stable angina pectoris]. AB - Seventy seven males aged under 60 years with Functional Classes II-IV stable angina were examined. The patients were randomly divided into 3 groups: 1) 24 patients receiving drug therapy alone; 2) 27 patients taking drug therapy in combination with hyperbaric oxygenation; and 3) 26 patients having drug therapy in combination with hemosorption. In all the patient groups, there was a reduction in the frequency of resting and exercise anginal attacks, in Group 3, exercise tolerance was increased due to drug therapy. In a re-examination, there was a significant fall in total cholesterol and high-density lipoprotein cholesterol levels only in Group 3. A comparison of daily drug doses indicated that the functional class improved only due to the adequate antianginal therapy. Thus, hyperbaric oxygenation and hemosorption have no significant action on the degree of stable angina. PMID- 1753613 TI - [The effect of finoptin on platelet aggregation, blood coagulability and fibrinolysis in patients with ischemic heart disease during physical exercise]. AB - Exercise platelet aggregation, blood coagulability, and fibrinolysis were examined in patients prior myocardial infarction 2-3 months following the disease. Seventy patients of whom 35 had received placebo and 35 finoptin prior to exercise were studied. The platelet aggregation, blood coagulability, and fibrinolysis were explored before and after bicycle ergometric test. Following exercise, the patients on placebo showed higher platelet aggregation, blood coagulability and lower fibrinolysis, whereas those on finoption exhibited a lower increase in platelet aggregation and blood coagulability and activated fibrinolysis. PMID- 1753614 TI - [Selection of ischemic heart disease patients with ventricular tachycardias for surgical therapy]. PMID- 1753615 TI - [Development of arrhythmia in patients after heart surgery in relation to the length of the Q-T interval]. AB - To predict intra- and postoperative ventricular arrhythmias, the length of Q-T interval was determined in 29 patients after cardiosurgical interventions made under artificial circulation by using ECG monitoring. The occurrence of ventricular arrhythmias were found to be related to a Q-T interval index of more than 20% of the normal value. The application of simple computer systems allows the Q-T interval to be monitored on line, identifying patients at a high risk for arrhythmias and using an adequate antiarrhythmic therapy. PMID- 1753616 TI - [Dilated cardiomyopathy: clinical and morphologic aspects]. PMID- 1753617 TI - [Hemodynamic and oxygen supply during exercise in patients with cardiac pacing during treatment of heart failure]. AB - Invasive and non-invasive tools were used to examine the specific features of exercise hemodynamic and oxygen supply in time in 25 patients with heart failure who underwent permanent pacing during a long-term glycoside and vasodilator therapy. It is shown that treatment with glycosides and vasodilators should be used in patients having severe myocardial systolic dysfunction and undergoing pacing. In the absence of this abnormality, it is advisable to use peripheral vasodilators (corvaton or sydnopharm) and diuretics for a long time. PMID- 1753618 TI - [Pathologic movements of the ventricular septum in complete block of the left branch of the bundle of His and their effect on left ventricular function]. AB - Echocardiographic tools (M-mode and 2D-scanning) were applied to examine 83 patients with complete bundle-branch block and/or its anteroapical bifurcation block. Six types of abnormal ventricular septal motions associated with the intraventricular asynchronism typical of complete bundle-branch block and with the specific features of electric pulse propagation in the His-Purkinje system were identified. There was a reduction in left ventricular ejection fraction that is peculiar to Types I and VI abnormal ventricular septal motions, whereas in patients with complete bundle-branch block, it is associated with anteroapical bifurcation block. A moderate decrease in ejection fraction is more common for Types III and IV abnormal ventricular septal motions (despite the severity of cardiac disease). Complete bundle-branch block alone and in combination with anteroapical bifurcation block contributes to a decrease in left ventricular function and diminished myocardial contractility. Whether the severity of complete bundle-branch block affects cardiodynamics is discussed in the present paper. PMID- 1753619 TI - [Electrocardiographic signs of first degree sinoatrial block]. PMID- 1753620 TI - [Surgical treatment of supraventricular tachycardias in children]. AB - The paper deals with the results of surgical treatment in 19 children with supraventricular tachycardias. Eighteen patients were found to have the Wolff Parkinson-White syndrome and one presented with ectopic right atrial tachycardia. The accessory pathways in the free wall and anterior septum in the presence of the Wolff-Parkinson-White syndrome were eliminated on the working heart, whereas those in the posterior septum were removed during extracorporeal circulation via endocardial access. Ectopic right atrial tachycardia was arrested by arrhythmogenic area resection in the right atrium during extracorporeal circulation. A positive result of the operation was achieved in 17 of the 18 patients. At day 2 of postsurgery, one patient developed recurrent tachycardia that was eliminated during a repeated operation. Which optimal method should be chosen to remove accessory pathways is discussed in the paper. PMID- 1753621 TI - [Blood pressure changes induced by various exercise regimes in patients with "mild" arterial hypertension]. AB - How two regimes of exercise training affect blood pressure changes was examined in 70 individuals with mild arterial hypertension. Prolonged controlled exercise training were shown to be an effective tool of non-drug correction of elevated blood pressure, the exercises aimed at developing aerobic tolerance being more beneficial. The magnitude of changes (increase) of working capacity may be an indicator for the effectiveness of exercise training programmes. PMID- 1753622 TI - [Comparative epidemiology of arterial hypertension in the native and migrant male population of Chukotka and Novosibirsk]. AB - The paper provides the results of a prospective epidemiological study of the prevalence of arterial hypertension in three populations: Chukotka's aborigines and migrants and a Novosibirsk's population. The most unfavourable epidemiological situation for arterial hypertension was found to be in migrant males aged 30-59 years. A medical examination is proposed among young migrants in the first years of adaptation in the North. PMID- 1753623 TI - [Specifics of arterial hypertension in the migrant population of Chukotka]. PMID- 1753624 TI - [Prognostic significance of plasma renin activity and aldosterone levels in patients with chronic cardiac insufficiency]. AB - Minor biochemical changes in the renin-angiotensin-aldosterone system play a significant role in the formation of clinical chronic heart failure (CHF). Classifying heart failure by the activity of plasma renin identifies 3 large patient groups that are characterized by low, normal or high renin activity. If aldosterone is included into its characterization, the groups should be divided into subgroups by plasma aldosterone levels. The biochemical "profiling" of patients in terms of renal and adrenal hormones may be widely applied to the prediction and individually selected therapy of CHF patients. The present study has demonstrated that in contrast to individuals with normal or high renin activity and of the same age and the same degree of heart failure, patients with its low levels are better protected against arrhythmias and severe and therapy resistant heart failure. In severe CHF aldosterone concentrations are virtually higher at any time. PMID- 1753625 TI - [Acetaldehyde in the cardiotoxic mechanism of action of alcohol: effects on cardiac and adrenal catecholamines]. AB - How the levels of rat cardiac, adrenal, and epinephrine and norepinephrine change with acetaldehyde and ethanol given alone or in combination during their acute and chronic administration was examined. In some series of experiments, acetaldehyde and ethanol were used in combination with teturam. The findings suggest that the coupling of two negative processes--a reduction in cardiac norepinephrine levels, which is associated mainly with the effects produced by ethanol, and an increase in epinephrine concentrations, which is apparently induced by acetaldehyde--may be one of the mechanisms responsible for cardiovascular abnormalities in alcoholic intoxication. Acetaldehyde modifies the regulatory effect of the sympathoadrenal system on cardiac function, causing adrenal catecholamine imbalance. PMID- 1753626 TI - [Late ventricular potentials: electrophysiologic basis, recording methods and clinical significance]. PMID- 1753627 TI - [Psychosocial factors in sudden cardiac death]. PMID- 1753628 TI - [Clinical effectiveness of domestic lidocaine]. PMID- 1753629 TI - [Has S. S. Iudin created a surgical school?]. PMID- 1753630 TI - [Blood reinfusion in stab-incision heart injuries]. AB - The authors had 110 patients with heart injuries (HI) under observation. The blood loss was, 1,092 +/- 120 ml in isolated HI and 2,410 +/- 246 ml in combined HI. Blood reinfusion (BR) was performed during 91 operations, the average volume was 1,233 +/- 215 ml. The peculiarities of reinfusion techniques are analysed and its advantages and shortcomings are critically appraised. The causes of fatal outcomes are shown according to the character of the heart damage and the volumes of blood loss and reinfusion. Mortality in HI with the use of BR was 16.5%. PMID- 1753632 TI - [Auto-dermal monophilic plastic surgery of ventral hernia]. AB - To improve the results of surgical management of postoperative ventral hernias, the authors applied their suggested variant of autodermic plasty of the hernial openings. The method consists in using for the plasty a band or graft of autologous skin armored with a monophilic thread. To reduce lymphorrhea the autodermic graft was covered with a hernial sac on a pedicle. The method was applied in 93 patients with good late-term results. The number of postoperative complications reduced to 3.5% and mortality to 1%, recurrences were not encountered. PMID- 1753631 TI - [Magnetic resonance tomography in the diagnosis of surgical diseases]. AB - The authors analyse the first experience in the use of magnetic resonance tomography (MP-tomography) in the diagnosis of some surgical diseases. MR tomography of the mammary gland (257 patients), thymus (55 patients), adrenals (41 patients), and hypophysis (18 patients) was conducted. The results of the examination were compared with the findings of other diagnostic methods and verified intraoperatively and histologically. The authors claim that the high informativeness of MR-tomography, its noninvasiveness, the absence of a radiation load, and the possibility of repeating the examination many times in three mutually-perpendicular planes distinguish the method favorably and dictate the necessity of its further study in clinical medicine. PMID- 1753633 TI - [Complications of wound healing after appendectomy. Medical and economic aspects]. AB - The incidence of hospital and posthospital wound complications was studied in 236 patients, residents of Zelonograd, who underwent operation for acute appendicitis. The material was collected at City Hospital No. 3 and four out patient clinics of Zelenograd. The incidence of suppuration of the surgical wound in the hospital period was 13.1%, that of nonpurulent complications was 9.3%, and the total incidence of the wound complications was 22.4%. In the posthospital period additional suppuration of wounds was encountered in 23.3% of patients, nonsuppurative wound complications in 17.1%, and the total incidence of posthospital wound complications was 40.3%. The frequency of rehospitalization was 5.5%, the incidence of postoperative hernias was 0.9%. The economical loss due to the development of wound complications in 236 patients operated on for acute appendicitis came up to 56,120 roubles. PMID- 1753634 TI - [Role and significance of S. S. Iudin in the development of reconstructive surgery of the esophagus]. AB - Merits can be conferred upon S. S. Yudin not only in the improvement of the method of esophagoplasty with the small intestine suggested by C. Roux in 1907, but also in the development of reconstructive surgery of the esophagus on the whole. Although new methods for esophagoplasty have been suggested and new technical possibilities have appeared, many elements of surgical tactics, operative techniques, and instruments suggested by S. S. Yudin are still applied in reconstructive surgery of the esophagus. Among them are the detailed description of jejunal architectonics from the surgeon's point of view, the wide use of test compression of the mesenteric vessels to evaluate the adequacy of blood supply to the graft, description of the clinical signs of disturbed blood supply to the graft, etc. S. S. Yudin laid the foundations of scientific research into the morphological and functional reorganization of organs and tissues in prolonged existence under unusual conditions, which is of great theoretical importance. Twenty-year experience in reconstructive surgery of the esophagus allow the author of this article to appraise at their true worth the technical procedures and physiological approaches suggested by S. S. Yudin, which are being developed further under modern conditions. This applies to substantiation of the most reliable and physiological method of retrosternal esophagoplasty with the colon with isoperistaltic position of the graft, transpleural resection of a cicatricially deformed esophagus, surgical treatment of achalasia of the superior esophageal sphincter. PMID- 1753635 TI - [Improvement in transfusion therapy tactics in the control of suppurative infectious complications]. AB - A pathogenetically substantiated multicomponent infusion-transfusion therapy for surgical patients with pyoseptic complications is suggested with consideration for the correction of all the links of homeostasis. The authors give a concrete scheme of multicomponent infusion-transfusion therapy as it is applied day by day, with due regard for the set of necessary transfusion media, their volume, the number of times that they are infused, and the order of their use. The favourable experience in the application of infusion-transfusion therapy in 421 patients is discussed. PMID- 1753636 TI - [Prevention and treatment of early complications in patients after reconstructive surgery of the esophagus]. AB - The work deals with clinical appraisal of the course of the early postoperative period and the prevention and treatment of complications after reconstructive operations on the esophagus. The postoperative period was studied in 99 patients. Complications occurred in the early postoperative period in 48.5% of patients, obstructive processes in the lungs were of principal importance among them. The authors conclude that particular significance in the prevention of acute respiratory failure in patients after one-stage plasty of the esophagus should be attached to the early diagnosis of pulmonary complications, prolonged artificial lung respiration, and measures for maintaining normal passage of the respiratory tract (cleansing bronchoscopy, early activation of patients, adequate anesthesia). The main importance in reducing mortality after one-stage esophageal plasty belongs to the measures of prevention and treatment of incompetence of the sutures of the esophageal anastomosis and mediastinitis. PMID- 1753637 TI - [Surgical treatment of acute complications of gastroduodenal ulcer]. AB - Operations were carried out on 258 patients with perforating ulcer and on 256 patients with acute bleeding from the ulcer. Perforating ulcer was managed by its closure with sutures in 226 patients (87.6%), by its excision with pyloroplasty and vagotomy in 4 (1.5%), and by primary resection of the stomach in 28 patients (10.9%). Postoperative mortality was 4.65%. In acute hemorrhage 221 patients (86.3%) were subjected to resection of the stomach, 6 (2.4%) to vagotomy with economical resection of the stomach, and 29 patients (11.3%) to excision of the ulcer or stitching of the bleeding vessel. The postoperative mortality was 7.8%. PMID- 1753638 TI - [A comparative study of immobilizing properties of the "boot" plaster bandage after manual and device reposition of fractures of the malleolus]. AB - The article deals with the comparative evaluation of the immobilizing properties of the "boot" plaster bandage after manual and apparatus reposition of the malleoli. It was revealed by means of the EMED and F P/10 apparatus (FGR) that the immobilizing property of the "boot" plaster bandage is higher in apparatus than in manual reposition. PMID- 1753639 TI - [Treatment of "difficult" duodenal stump]. AB - The Plenk method in the author's modification was successfully applied in resection of the stomach "for exclusion" in 22 patients. When there was a threatening incompetence of the duodenal stump sutures, to prevent generalization of peritonitis the stump in 24 patients was covered with a "hood" of the greater omentum and external drainage of this space was installed; the procedure was an alternative of duodenostomy. Incompetence occurred in 3 cases with subsequent recovery. In resection of the stomach for recurrent ulcer after previous vagotomy combined with gastroduodenostomy after Jaboulay, the defects in the duodenal wall were closed with a demucosed antral-pyloric gastric segment after the author's method. The operation was conducted on 4 patients. PMID- 1753640 TI - [A method of suturing penetrating ulcers of the duodenal bulb]. AB - The author developed a method for plastic treatment of the niche of a duodenal bulb ulcer, particularly when it is a source of profuse bleeding, when the ulcer is located on the posterior wall or penetrates into the head of the pancreas. The method is based on operation for bilateral subdiaphragmatic selective vagotomy and Finney's pyloroplasty. In performing the above procedure a pyloroduodenal spur is formed by a method modified by the author by making an incision through the pylorus closer to the lesser curvature of the stomach. As a result the formed pyloroduodenal spur is of a sufficient length and can be easily displaced into the bulb to the ulcer. The ulcer with the bleeding vessel is stitched through with Halsted's or Z-shaped sutures and the pyloroduodenal spur is sutured with the same sutures to the ulcer, effecting tamponade of its whole surface. When combined with selective vagotomy the method ensures reliable hemostasis. The method was applied with a favorable outcome in an 83-year-old patient followed up for 12 months. PMID- 1753641 TI - [52 years with antethoracic small-intestine esophagus]. PMID- 1753642 TI - [Radical enucleation of gastrinoma with conservative surgery of the stomach]. PMID- 1753643 TI - [Covered perforation of recurrent duodenal ulcer after vagotomy with pyloroplasty]. PMID- 1753644 TI - [S. S. Iudin's letter to Academician N. N. Burdenko]. PMID- 1753645 TI - [Sketches of gastric surgery]. PMID- 1753646 TI - [Tietze's syndrome]. PMID- 1753647 TI - [New types of intestinal suture (review of foreign literature)]. PMID- 1753648 TI - [Role of S. S. Iudin in the development of emergency anesthesiology at the Moscow Sklifosovskii Research Institute of Emergency Care]. AB - S. S. Yudin was concerned about the problems of anesthesia from as early as the twenties. Under the term "anesthesia" he combined a whole complex of measures including preoperative management, the production of insensibility to pain, and intraoperative treatment and supported in this manner the creation of anesthesiological care, which was organized at the Sklifosovsky Research Institute of Emergency Care in 1959. The object of all practical and scientific activity of the care was the creation of simple, popular, and effective variants of anesthesia with consideration for the variety of pathophysiological responses. The principal responses are shock, hypovolemia, insufficiency of respiration and gas exchange, inversion of metabolism, intoxication, intracranial hypertension, the compression-dislocation syndrome, and hepatorenal failure. Study of the effect of anesthetics on various organs and systems of the organism made it possible to determine the tactics and methods of anaesthesia for patients with trauma and diseases of the abdominal and thoracic organs, central nervous system, and locomotor apparatus. PMID- 1753649 TI - [Spinal anesthesia]. AB - The article deals with some aspects of spinal anesthesia. It analyses in the light of possible complications the results of spinal anesthesia conducted in 4,186 cases with 1% sovcaine (cinchocaine hydrochloride) solution and 5% novocaine (procaine hydrochloride) solution by 60 surgeons. Spinal anesthesia was applied in patients, whose ages ranged from 11 to 96 years, in various operations. Contraindications for the method were determined. The author appraises comparatively spinal anesthesia with the related peridural anesthesia and discusses the prospects of the development of the method with the existence of new anesthetics and very thin needles for puncture of the subarachnoid space, which leads to the minimum number of possible complications. PMID- 1753650 TI - [Features of general anesthesia and infusion-transfusion therapy in extensive surgery of the organs of the abdominal cavity]. AB - The article discusses variants of infusion-transfusion therapy (ITT) in early stages of expanded operations on the abdominal organs attended by massive blood loss (2 to 4 BCV and more). Seventy-three patients were examined, they underwent resection of the liver (30), pancreatoduodenal resection (37), or removal of a retroperitoneal tumor (6 patients). On the basis of precise study of central and peripheral hemodynamics, acid-base equilibrium, and blood oxygen transport function the authors find it necessary to increase the volumes of ITT to 70-80% BCV in the first stage of the operation with a colloid/crystalloid ratio of 1:4. The described method makes it possible to avoid critical fluctuations of cardiac output and blood pressure in massive bleeding. At the same time, such hemodilution causes no considerable decrease in hemoglobin concentrations (which was 79.0% of the initial level at the beginning of the main stage) and specific oxygen transport (85.0%, respectively). In absolute expression the specific oxygen transport before the hemorrhage is 465 + 29 ml/min/m2, which significantly exceeds the critical value. The authors believe the ITT method to be indicated in inevitable blood loss and absence of serious cardiovascular diseases. From comparative analysis of the different variants of general anesthesia, the authors conclude that the following combination of agents is preferable for the discussed category of patients: phentanyl, droperidol, seduxen, kalipsol (ketamine), and dalargin. Their balanced use ensures stability of the main homeostasis indices in all stages of the intervention; the hepato- and pancreatoprotective properties of dalargin are also of importance. PMID- 1753651 TI - [Hemostasis in hemorrhage from varicose veins of the esophagus and stomach]. AB - The results of treatment of 15 patients with bleeding from varicose veins of the esophagus and stomach are discussed. Blakemore's tube and endoscopic sclerosing of the veins with 3% Thrombovar solution were applied for hemostasis. It is concluded that nonoperative measures are preferable. The most effective method of hemostasis in intensive bleeding is the use of Blakemore's tube for temporary arrest of bleeding followed by endoscopic sclerosing for preventing recurrent hemorrhage. PMID- 1753652 TI - [Extensive lymph node excision in the surgical treatment of esophageal and gastric cancer]. AB - Experience with 100 operations for carcinoma of the esophagus and stomach with expanded lymphadenectomy is analysed. The operative techniques are described and the necessity and expediency of expanded lymphadenectomy, the method of its performance, classification of the group of lymph nodes which must be removed are discussed. The postoperative mortality was 2%, complications in the postoperative period 25%. Metastases in the lymph nodes were confirmed histologically in 69% of cases. It is concluded that expanded lymphadenectomy is a necessary measure in surgical intervention in patients with carcinoma of the esophagus and stomach and improves the results of management of this group of patients. PMID- 1753653 TI - [Sergei Sergeevich Iudin (a centennial of his birth)]. PMID- 1753654 TI - [Diagnosis and surgical treatment of reflux esophagitis]. AB - Operations were performed on 192 patients with reflux esophagitis, 23 of them had peptic stricture of the esophagus. Esophago-fundoplication was the main operation. Nissen's (106), Tupe (47), Belsi's (3), Dor's (5), and atypical methods were applied. Whenever indicated it was supplemented by crurorhaphy, SPV, pylorotomy, correction of the duodenal junction, etc. Resection of the esophagus (19) was performed with one-stage esophagoplasty by means of the stomach through a left thoracoabdominal approach (14), the whole stomach passed through the posterior mediastinum from an abdomino-cervical approach (2) and the whole stomach with Lewis' intrathoracic anastomosis (3). Distal gastric resection was carried out in 6 and other operations in 3 patients. The mortality was 1%. Reoperations were performed in 5 patients. The results were good in 81.2% of cases. The tactics is individualized according to the presence or absence of a stricture, its length, and localization of the upper border. PMID- 1753655 TI - [A variant of an operation of varicose veins of the esophagus and cardia in patients with portal hypertension syndrome]. AB - On analysing universal experience, the authors suggest their variant of operation on varicose veins of the esophagus and cardia with the use of Doppler ultrasonography and intraoperative packing of the veins with a radiocontrast foamy polymer. With this method the flow of blood in the venous collaterals of the stomach and esophagus can be arrested more radically during the operation, which considerably reduces the percentage of recurrent bleeding from these veins. PMID- 1753656 TI - [Course of wound process in chemical burns of the stomach (results of morphological and endoscopic studies)]. AB - The dynamics of the wound process in chemical burns of the stomach were studied on the basis of histological and endoscopic examinations. The patients who were studied were given nonoperative treatment, in all cases for corrosive gastric ulcers. The most frequent complications were cicatricial stenoses (86.6%) in involvement of the antral part of the stomach. Regeneration of the damaged tissues of the gastric wall was disturbed, the specific features of these disorders were studied. PMID- 1753657 TI - [Formation of horizontal esophago-small intestine anastomosis in gastrectomy for cancer]. AB - A new modification of horizontal esophago-enterostomy has been introduced into clinical practice. The operative techniques is described in detail. Gastrectomy was performed in 76 patients for carcinoma; there were 49 males and 27 females whose ages ranged from 39 to 70 years. Such complications as incompetence of the sutures of the anastomoses did not occur in the immediate postoperative period. Examination of patients in follow-up periods of 4 weeks to 2 years after the operation revealed neither cicatricial stenosis of the esophago-enteric anastomosis nor reflux esophagitis. PMID- 1753658 TI - [Diagnosis and treatment of gastrointestinal hemorrhage]. AB - The article analyses the results of treatment of 4,430 patients with gastrointestinal bleeding in the last four decades. Two periods, from 1950 to 1969 and from 1970 to 1990, are compared from the standpoint of change of the disease structure, the methods of diagnosis and hemostasis. The number of hemorrhages of ulcer genesis reduced from 80 to 40.3%. Changes in the pattern of the disease is associated with improved diagnostic methods and recognition of pathological processes which were previously inaccessible to radiological examination, such as the Mallory-Weiss syndrome, acute ulcerations of the mucosa. The age composition remains relatively stable. Just like in the previous years, each third patient is over 6.0 years of age. Despite introduction of new methods of treatment, such as endoscopic arrest of bleeding, enteral feeding, a new method for management of penetrating ulcers and others, the mortality rate reduced only from 4.5% (1950-1969) to 3.4% (1970-1990). It is noted, however, that fatal outcomes in the last years prevail among patients aged 65-70 or older. PMID- 1753659 TI - [Surgical treatment of alkaline gastritis]. AB - A method for reconstructive operation on the stomach with formation of a Y-shaped anastomosis in patients with alkaline gastritis is discussed. The author suggests that the an area of the mesentery with the least number of vessels should be chosen between the vascular arcade and two arteries of the jejunum (at a distance of 12-15 cm from the ligament of Treitz) and then dividing the mesentery parallel and medial to the vascular arch. Maximal maintenance of blood supply and innervation of the loop isolated after Roux ensured good operative results in 84 patients. PMID- 1753660 TI - [Treatment of Mallory-Weiss syndrome by endoscopic diathermocoagulation]. AB - The work analyses the results of treatment of 111 patients with the Mallory-Weiss syndrome by endoscopic diathermocoagulation. It proved ineffective from the very beginning in 11 (9.9%) cases, in another 23 (20.7%) patients hemorrhage recurred in the immediate 4 days but in one third of them its source was another disease. The follow-up of 77 patients revealed recurrence of the disease in the late-term period (from 12 months to 9 years) after diathermocoagulation in 12 (15.6%), but only 2 of them had to be operated on. The operative mortality was 17%, but when surgery was combined with diathermocoagulation the mortality rate was 4.5%. PMID- 1753661 TI - [S. S. Iudin's views on the problems of anesthesia]. AB - The article expounds S. S. Yudin's views on problems of anesthesia in various periods of his surgical activity: ideas on the necessity of introducing modern multicomponent endotracheal anesthesia were expressed before the mid-forties. S. S. Yudin's experience in applying spinal anesthesia gave rise today to the wide use of epidural anesthesia. PMID- 1753662 TI - [Individual choice of ribonuclease and fluorofur doses in the treatment of patients with acute pancreatitis]. AB - A method is suggested for individual calculation of optimal doses of ribonuclease and fluorofur on the basis of a standardized index--the degree of severity. A CM 1404 computer was used in solving the problem. From analysis of 500 case records by means of programs of discriminant and multidimensional linear regressive analysis a mathematical dependence was found between some parameters indirectly reflecting the severity of the patient's condition, the ribonuclease dose, and the efficacy of the treatment. A similar dependence for fluorofur was also studied. The discovered statistical regularity was realized as a nomogram for calculating the degree of severity and individual optimal doses of ribonuclease and fluorofur. The method was used in 114 patients. All the compared indices were found to be better than those in the group of patients for whom the dose of the agents (ribonuclease) was calculated on the basis of a constant dose per kg weight. PMID- 1753663 TI - [Improvement of infusion-transfusion therapy in a multidisciplinary emergency care hospital]. AB - The article deals with the analysis of works of S.S. Yudin's students and followers devoted to scientific practical and scientific-organizational research into optimization of infusion-transfusion therapy in emergency service hospitals in emergency states: multiple and combined trauma, the crush syndrome, burns, exogenous poisoning, and pyoseptic complications in surgical and traumatological practice. The principles of transfusion media rationing in an emergency service hospital, particularly in mass admission of patients and accident victims, are substantiated. The medico-economical efficacy of including infusion-transfusion therapy in complex treatment of emergency conditions is shown. PMID- 1753664 TI - [Effects of surgical intervention and intravascular irradiation of blood with helium-neon laser on the state humoral autoimmunity in oncological patients]. AB - Humoral autoimmunity of patients with malignant gastrointestinal tumors was studied by different variants of enzyme immunoassay. In the preoperative period the frequency of detecting autoantibodies binding to DNA and components of external and internal membranes of cells of different tissues was not higher in patients (n-55) than in donors (n-45). Beginning from the 7th postoperative day all patients were found to have a significantly increased level of autoantibodies to DNA (p less than 0.01), fibroblasts (p less than 0.01), hepatocytes (p less than 0.01), islet cells (p less than 0.01), hepatic or pancreatic microsomes (p less than 0.05). There was a tendency towards normalization of these level by the 21st day in all cases. In patients (n-10) treated by blood intravascular laser irradiation after the operation the level of IgG (but not IgM) autoantibodies to DNA by the 14th postoperative day was significantly (p less than 0.01) higher than that in patients whose blood was not exposed to radiation. It is suggested that the discovered humoral immune reaction is a necessary component of wound immunity and develops in response to hetero-organic autoantigens which are unmasked in injury of the tissues during the operation. Laser therapy ensures a more intensive development of this reaction without altering its direction. PMID- 1753665 TI - [Effects of intravascular laser irradiation of blood on the state of the immune system of patients with chronic osteomyelitis]. AB - The authors discuss the results of study of the immune status in 55 patients with chronic osteomyelitis, it was found that the condition of the patients' immune system reflects the duration and severity of the disease and the individual reactivity of the organism. The inclusion of laser treatment in the complex of therapeutic measures should be based on appraisal of the condition of the immune system and conducted under dynamic immunological control. In deficiency of the thymus-dependent immunity the sessions of blood intravascular laser irradiation activate the organism's defence forces and facilitate correction of the imbalance in the system of the regulating cells. Laser irradiation of blood in mild changes of the immunological status is expedient because it may lead to negative dynamics of the immune system. Attainment of an optimal immunological condition in the preoperative period is conductive to a favourable course of the postoperative period and a favourable outcome of the disease. PMID- 1753666 TI - [Excimer laser keratomileusis for myopia correction. Results and complications]. AB - Results of excimer laser keratomileusis in 26 myopic sighted eyes are presented. The follow-up was at least 9 months. The base-line refraction was -4.48 +/- 1.81 D (range: -1.4 to -9.25 D). After 3 months 85% were within +/- 1 D from the intended refraction. The such defined success rate after 6 months was 87.5%, after 9 months 88%, and after 12 months 92%. One month after surgery we found an overcorrection of +1.45 +/- 1.22 D decreasing to +0.27 +/- 0.94 D at three months, becoming an undercorrection of -0.24 +/- 0.76 D after six, and -0.32 +/- 0.69 D after nine months, and of -0.36 +/- 0.6 D after one year. Stability within the measurement error (+/- 0.25 D) appeared in 79% of the treated eyes six months after treatment. Three patients have been excluded from the study group because they did not follow the protocol. Subepithelial haze occurred in all patients, becoming most intense after 3 months, gradually clearing over the next months. With appropriate steroid medication, the refractive effect may be modulated. Complications as steroid glaucoma, recurrent erosion, loss of acuity, or extensive corneal scarring seem to be very rare. PMID- 1753667 TI - [Clinical study of the effectiveness of a preservative-free tear substitute]. AB - 57 patients with dry eye syndrome of various etiology were treated with a preservative-free hydrogel in an open clinical trial. All patients enrolled in the 12 weeks study had a history of pretreatment with usual commercial tear substitutes which was either insufficient for relief of complaints or caused hypersensitivity. Detailed analysis of patients self assessment of their condition (by means of a linear scale), tear film break-up time, Schirmer Test, and physician's assessment of therapeutical results revealed that in about 90% of cases existing patient complaints and findings related to dry eye syndrome were significantly improved by symptomatic therapy with this preservative-free gel. PMID- 1753668 TI - [Clinical follow-up, histologic findings and therapeutic problems in a patient with bilateral ulcus rodens Mooren]. AB - A severe, spontaneously acquired, bilateral, sight threatening Ulcus rodens Mooren of a 31 years old type I diabetic will be demonstrated in its clinical course. An improvement was achieved by a systemic immunomodulating therapy with Ciclosporin A that had to be tapered after 3 weeks due to severe side effects. The exclusive local therapy showed no effect at all. Later, the patient underwent a penetrating keratoplasty and extracapsular cataract extraction of both eyes under systemic Ciclosporin A therapy. The graft of the left eye failed due to a foudroyant bacterial infection whereas the keratoplasty of the right eye was successful up to this day despite of various complications. PMID- 1753669 TI - [Fluorescein angiography findings after retinotomy and retinectomy]. AB - Drainage-retinotomies and relaxing retinectomies are helpful techniques in extreme vitreoretinal surgery. They have become established as a surgical instrument, but their possible pathophysiologic effects on the retina, pigment epithelium and choroid have not been investigated as yet. 30 Patients with retinotomies or retinectomies after vitrectomy with silicone oil filling for advanced proliferative vitreoretinopathy were studied angiographically. Fluorescein angiographic findings revealed 1. a predominant effect of endophotocoagulation in the area of the retinotomy/retinectomy with occlusion of the choriocapillaris and hyperpigmentation and window effects of the retinal pigment epithelium, but sometimes there was a localized traction effect with retinal and choroidal folds, 2. that retinal perfusion is unaffected in untreated and coagulated areas without evidence for a breakdown of the blood-retina-barrier or retinal ischemia, 3. an intact blood-retinal-barrier in areas of uncovered retinal pigment epithelium, 4. no evidence for significant reproliferations in the areas of retinotomies and retinectomies, 5. choroidal neovascular membranes which may occur postoperatively at the retinotomy site probably as a complication for intraoperative injury of Bruch's membrane, 6. a cystoid macular edema, an optic atrophy, pigment-fallout, depigmented tracks and choroidal folds as unspecific findings post retinal detachment surgery. The angiographic data support the clinical impression, that retinotomies and retinectomies performed in otherwise untreatable cases cause no significant damage in the attached retina. PMID- 1753670 TI - [Significance of the corneal thickness in non-contact tonometry]. AB - In this study the Reichert non-contact tonometer (NCT II) was compared with the Goldmann applanation tonometer (GAT) in 25 subjects (50 eyes; pressure range 9-17 mmHg). The relationship NCT/GAT fulfilled the conditions required for legal verification. Marked differences between the readings of both instruments can be caused by anomalous central corneal thickness, because non-contact tonometry is influenced more than conventional applanation tonometry by the corneal thickness. Starting from a central thickness of 0.51 mm, the NCT is assumed to underestimate the actual intraocular pressure in eyes with thinner and to overestimate it in eyes with thicker cornea by 1 mmHg per 0.01 mm difference of corneal thickness. This value changes with individual corneal tissue qualities and is not valid especially in presence of corneal edema. PMID- 1753671 TI - [Distribution of melanoma-associated antigens (HMB 45 and S 100) in benign and malignant melanocytic tumors of the conjunctiva]. AB - The reactivity of the monoclonal antibody HMB 45 was evaluated in melanocytic tumors of the conjunctiva. Among these are 10 acquired melanoses, 19 nevi and 34 melanomas. Results were compared with the presence of the S 100 antigen. Especially the intraepithelial and junctional components of primarily benign lesions were stained with HMB 45. Within malignant melanoma this antibody reacts with melanocytes in the epithelial, junctional and subepithelial areas. The polyclonal antibody S 100 stains all melanocytes in pigmented lesions of the conjunctiva. Intraepithelial or subepithelial malignant infiltrating tumor cells show very intense staining with HMB 45. HMB 45 has therefore high specificity for stimulated melanocytes, but it does not distinguish benign and malignant proliferating melanocytic cells. PMID- 1753672 TI - [Local prevention with interferon of "epidemic" conjunctivitis caused by a currently unidentifiable virus]. AB - Topical Interferon application did effectively interrupt the further clinical spread of a highly contagious viral keratoconjunctivitis. A total of 130 endangered inpatients, still free from symptoms, were treated with one drop per eye daily for a period of 12 days. 123 patients stood free from any further infection. Only during the first two days after the beginning of the Interferon prophylaxis 7 inpatients showed an acute viral keratoconjunctivitis still. Obviously these patients were infected prior to the prophylactic therapy and were just in the incubation period. We conclude that Interferon eye drops (one drop per eye daily) may offer a reliable protection from exogenous viral infection. Certainly this protection comes too late if the patient's incubation period has already started. PMID- 1753673 TI - [Spontaneous bilateral lens resorption in a case of Hallermann-Streiff syndrome]. AB - The Hallermann-Streiff-syndrome was first described in 1948 by Hallermann and in 1950 by Streiff. The most common features are dyscephalia, cataract, microphthalmia, dental anomalies, hypotrichosis, cutaneous atrophy, and nanism. Anomalies of the eye include cataract, microphthalmia, nystagm, strabism, blue sclera, fundus anomalies and combined anomalies of all segments of the eye. The frequency of cataract is about 90%. Spontaneous resorption of the lens is described in about 8%. We present a five year old girl showing the typical dyscephalia of the Hallermann-Streiff-syndrome (bird face). Her lenses were replaced by opaque membranes. These membranes presumably were remnants of the posterior lens capsule. PMID- 1753674 TI - [Treatment of Goldmann-Favre syndrome with cyclosporin A and bromocriptine]. AB - Up to now several reports have described a disturbance of humoral and cellular immune response in patients with tapetoretinal degeneration, but a pathogenetic relation of the described immunological changes to the retinal disease was not established. Therefore immunosuppressive treatment has not been advocated for degenerative vitreoretinal disease. We now report about the natural course of Goldmann-Favre's vitreo-retinal degeneration and the results of a therapeutical trial with cyclosporin A and bromocriptine in two patients. Without therapy we saw a slowly progressive flat central retinoschisis with a serous macular exsudation in fluorescein-angiography. Additionally we found peripheral vitreoretinal changes, mild cellular vitreal infiltration, extinguished electro retinogram and disturbed dark adaptation. Visual acuity and visual field were quite stabile. Under therapy with cyclosporin A we found a regression of the macular edema and flattening of the retinoschisis. One of the two cases showed a good improvement of visual acuity, in the other case a clear subjective improvement did not correlate with an increase in visual acuity. An additional therapy with bromocriptine did not bring further success, but we were able to reduce the cyclosporin A to a blood concentration of 70-100 ng per ml. PMID- 1753675 TI - [Occurrence of optic disk hemorrhage in the course of Vogt-Koyanagi-Harada syndrome]. AB - Cases, where in the course of Vogt-Koyanagi-Harada syndrome disc hemorrhages occur, are rare. One case was reported wherein about 2 weeks following the development of the disease, bilateral linear disc hemorrhages appeared and in 3 months disappeared, without sequellae of defective vision. PMID- 1753676 TI - [Temporary vision disorders, accentuated by deficient illness adjustment]. AB - A medical expert's opinion had to be given on five patients complaining about temporary visual disturbances. 1. Haze caused by keratoconjunctivitis sicca; 2. changing refraction related to diabetes; 3. phosphenes in a paralyzed monoculus; 4. double vision with fatigue in myasthenia; 5. presumed elevation of the risk for accidents in congenital nystagmus. The loss of earning capacity in these cases should be calculated as the mean of the earning capacity during the phases of least and maximal disturbance, if it is not yet included in the loss caused by additional stationary defects. Psychological adaptation to or an additional disturbance by the disease has to be considered and may justify a higher loss of earning capacity. PMID- 1753677 TI - [22nd annual meeting of the Society for Nephrology. Heidelberg, 15-18 September 1991]. PMID- 1753678 TI - New horizons in renal vasculitis. AB - After a long period during which few new data on the vasculitides emerged, the past decade has seen a real explosion of data on the subject. This began with basic clinical descriptions and the delineation of long term outcome as survival improved to a major extent under the influence of improved treatment regimes. In parallel, better understanding of the immunopathology has emerged. Of particular interest have been descriptions of autoantibody systems in vasculitis which seem to be specific to vasculitis and therefore diagnostically useful: the antineutrophil cytoplasmic antibodies (ANCA). Whether or not these are pathogenetically significant as well as useful remains a matter for debate. In parallel, anti endothelial cell antibodies have been described, but their role (if any), in pathogenesis remains equally obscure. There are some suggestions that vasculitis is becoming more common, but increased awareness and the availability of ANCA have undoubtedly increased awareness of the subject. PMID- 1753679 TI - Structure-function correlations in erythropoietin formation and oxygen sensing in the kidney. AB - The kidney is the main site of erythropoietin (EPO) formation. Oxygen sensing in the kidney itself plays a major role in the control of EPO synthesis. By in situ hybridization it has been established that the EPO-producing cells are situated in the interstitium of the cortical labyrinth, but they have not been precisely identified. Morphological findings provide new insights into the location and mechanism of oxygen sensing in the kidney. In addition to causing an increase in the number of cells containing EPO messenger RNA, anemia provokes structural changes exclusively in the cortical labyrinth. Specifically, the fibroblasts become enlarged and show increased activity of 5'-nucleotidase, and the S1 segment of the proximal tubule shows similar alterations as in various models of hypoxia. Thus, structures that are situated in the close vicinity of the EPO producing cells appear to be sensitive to decreased oxygen delivery. PMID- 1753680 TI - The progression of renal diseases: on the pathogenesis of renal interstitial fibrosis. AB - Renal interstitial fibrosis (RIF) frequently occurs in inflammatory and non inflammatory kidney diseases and is associated with a decline in renal excretory function. Fibroblasts which occupy the renal interstitium are involved mainly in the formation of RIF not only by the production of extracellular matrix, but also by regulatory processes. They respond to a variety of cytokines released by different cell types. To investigate mechanisms leading to RIF, immunohistochemical analysis and cell cultures of renal biopsies in various renal diseases have been performed. T lymphocytes are the major cells infiltrating the renal interstitium, and their number correlates with the impairment of renal function. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/-DP molecules, frequently associated with an aberrant expression of the intercellular adhesion molecule 1 (ICAM-1), was observed on proximal tubular epithelial cells, indicating that these cells may play a role in antigen presentation. The cell biological experiments revealed the presence of the three mitotic fibroblast types (MFI MFIII) and the three postmitotic types (PMFIV-PMFVI) in the cell culture. The number of fibroblasts in primary and passage-1 culture was increased seven-fold in cultures derived from kidneys with RIF (FKIF cells) in comparison to normal kidneys (NKF cells). FKIF cells show hyperproliferative growth and synthesize an increased amount of total collagen, especially types III and V. These cells express a protein, named "FIBROSIN", which seems to be specific for FKIF cells. Further extended cell biological analyses are currently being performed to investigate interactions of tubular cells, lymphocytes, macrophages, and fibroblasts in order to shed more light on the pathomechanisms involved in fibrogenesis leading to renal interstitial fibrosis. PMID- 1753681 TI - Renal blood flow control by tubuloglomerular feedback (TGF) in normal and spontaneously hypertensive rats--a role for dopamine and adenosine. AB - Following the elementary laws of hemodynamics and the functional characteristics of the renal myogenic and macula densa-mediated (TGF) vascular resistance control mechanisms, TGF-mediated changes of renal vascular resistance are amplified by cooperative changes of the myogenic mechanism. Myogenically induced changes, on the other hand, would be antagonized by TGF. Resetting of renal vascular flow resistance by alterations to the TGF mechanisms might thus be more effective than alterations to the myogenic mechanism. Dopamine and adenosine, two autacoids occurring normally in the tubular fluid, may play a key role in operating such a resetting mechanism. Dopamine and adenosine were found in proximal tubular fluid at concentrations of 10(-8) and 0.5 10(-6) M respectively. Dopamine inhibits the tubuloglomerular feedback mechanism, this inhibition is antagonized concentration dependently by adenosine. These effects most likely occur via D1 and A1 receptors and hence by regulation of the adenyl cyclase activity in the macula densa cells. The balance between adenosine and dopamine in tubular fluid appears to be under the control of extrarenal parameters. In normal rats, high dietary salt intake, by influencing the secretion of an unknown adrenal hormone, and inhibition of Na K-ATPase might be of importance. In spontaneously hypertensive rats unknown genetic parameters may also play a role. PMID- 1753682 TI - Are renal mechanisms involved in primary hypertension? Evidence from kidney transplantation studies in rats. AB - Previous renal transplantation experiments in genetically hypertensive and normotensive rat strains indicated that a genetic defect in the kidney may be primarily involved in the pathogenesis of primary hypertension. In order to investigate whether this is also true for the most widely used animal model of primary hypertension, the spontaneously hypertensive rat (SHR), we performed renal transplantations using SHR and normotensive Wistar-Kyoto rats (WKY) as kidney donors and bilaterally nephrectomized F1 hybrids, bred from SHR x WKY parents as renal graft recipients. Our studies were also designed to differentiate between primary and secondary renal mechanisms as a possible cause of posttransplantation hypertension. Recipients of renal grafts from adult, naive SHR but not from adult normotensive WKY kidney donors developed posttransplantation hypertension. Permanent blood pressure normalization by antihypertensive treatment in adult SHR kidney donors and prehypertensive, young age of SHR kidney donors reduced, but did not prevent, posttransplantation hypertension. Increasing renal perfusion pressure in WKY kidney donors (2-kidney 1-clip hypertension) also resulted in posttransplantation hypertension in recipients of the non-clipped kidneys. Blood pressure remained normal in recipients of renal grafts from young WKY kidney donors. These data suggest that SHR kidneys carry a genetic defect which may be primarily involved in the pathogenesis of primary hypertension. PMID- 1753683 TI - The endothelial L-arginine/nitric oxide pathway and the renal circulation. AB - Endothelial cells contain an enzyme(s) which produces nitric oxide from L arginine in response to a variety of mechanical stimuli as well as to autacoids and local and circulating hormones. Nitric oxide is a potent vasodilator and inhibitor of platelet function; it exerts its effects via activation of soluble guanylate cyclase and subsequent formation of cyclic 3'-5'-guanosine monophosphate. In the kidney, activation of the endothelial L-arginine pathway is associated with increases in renal blood flow, diuresis and natriuresis, while the glomerular filtration rate remains constant. The activity of the endothelial L-arginine pathway is impaired in hypertension and during chronic therapy with cyclosporine A. In addition, diabetes and atherosclerosis impair this pathway. Thus, the endothelial L-arginine pathway plays an important role in the local regulation of blood flow. Alterations in the activity of this pathway may play an important role in the pathophysiology of hypertension and renal disease. PMID- 1753684 TI - Lipid changes in the nephrotic syndrome: new insights into pathomechanisms and treatment. AB - The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism. Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipid-lowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates fatty acids, has been recently tested by the author, with very promising results. PMID- 1753686 TI - The incidence of Encephalitozoon cuniculi in a commercial barrier-maintained rabbit breeding colony. AB - Between 1982 and 1987 sera from 4952 New Zealand White rabbits (Oryctolagus cuniculus) obtained from a single commercial supplier were tested for the presence of antibodies to Encephalitozoon cuniculi. A commercially available carbon immunoassay test kit was used. Initially 32.9% of the rabbits were seropositive with the number progressively decreasing to 2.3% by 1987. The reason for the significant decline in the incidence of infection was most likely due to a selection process for breeding stock instituted by the supplier based upon productivity, posture and weight of each animal. PMID- 1753685 TI - Perspectives in transplantation immunology 1991. AB - The clinical success of organ transplantation depends to a large degree on the immunological acceptance of the grafted organ. This paper summarizes from an immunological point of view the recent progress that has been made to improve graft acceptance, and discusses some future aspects in the field. Over the last few years, major emphasis has been put on the development of new immunosuppressive drugs, including FK 506, rapamycin, and Deoxyspergualin. Together with monoclonal antibodies against defined T-cell surface antigens, there are now new and effective means available to prevent or treat rejection episodes. Progress has also been made in the field of HLA typing, where the introduction of molecular biology-based methods significantly increased the accuracy of HLA class II typing. The ultimate goal of transplantation immunology is the induction of (donor-) specific tolerance. While some protocols are effective in inducing peripheral tolerance in experimental animals, these regimens are at present not yet applicable in the clinical situation. To overcome the shortage of donor organs, alternative strategies are currently being considered. Among these, xenotransplantation may eventually prove successful, despite the massive immunological problems such as, e.g., the presence of preformed xenoreactive antibodies. PMID- 1753687 TI - Factors affecting the food intake, growth and protein utilization in the Helix aspersa snail. Protein content of the diet and animal age. AB - Food intake, growth and protein utilization were studied in the Helix aspersa snail by means of a nutritional balance experiment. This was designed in a 5 x 11 factorial arrangement involving 5 diets of different protein content (10.0, 12.5, 15.0, 17.5 and 20.0%) and 11 animal ages (ranging over 15 to 180 days of age). Dietary protein content and animal age determined food intake and protein utilization. The variations of dry matter and protein intake rates, growth rates, growth efficiency factors and protein retention rates, depending on dietary protein content or animal age were in agreement with what happens in other animals. These results suggest that there is no need to use diets with more than 17.5% of crude protein in these animals. PMID- 1753688 TI - Spontaneous uterine granular cell tumour in a Fischer 344 rat. AB - The microscopic features of a spontaneous uterine granular cell tumour in a Fischer 344 rat are described. The location of the tumour is novel for the rat. The neoplasm is characterized by the presence of cells with cytoplasmic granules which were PAS positive and diastase resistant. Electron microscopy and immunohistochemistry results are presented and the origin of the tumour is discussed. PMID- 1753689 TI - Mandible shape analysis in Y-congenic strains of mice. AB - In order to test for the presence of genes influencing morphology on the Y chromosome of mice, a canonical discriminant analysis of variation in mandible shape was conducted in 4 inbred strains of mice and 4 Y-chromosome congenic partners. Genetic background-dependent differences were observed, as well as a small sex variation in some strains, but it was impossible to detect any difference related to the between-strain exchange of the Y-chromosome. PMID- 1753690 TI - A simple method for the intragastric administration of drugs to fully conscious guineapigs. AB - The design and use of a simple system for the intragastric administration of miniature capsules or fluids to fully conscious guineapigs is described. The system is suitable for repeated drug administration. It causes minimal discomfort to the animals. PMID- 1753691 TI - Post-operative analgesia following thoracotomy in the dog: an evaluation of the effects of bupivacaine intercostal nerve block and nalbuphine on respiratory function. AB - Pain following thoracotomy reduces pulmonary ventilation in man and a similar effect is believed to occur in animals. The effects of two analgesic regimens on arterial blood gas parameters were studied in dogs following thoracotomy. Post Operative analgesia was provided with intermittent nalbuphine, either alone or in combination with an intercostal nerve block using bupivacaine. Arterial blood gas analysis was carried out at 4, 8 and 16 h post-operatively, both before the administration of nalbuphine and again 30 min later. Animals which received nalbuphine alone had a significant rise in arterial oxygenation following administration of this analgesic. This effect was not observed at 4 and 8 h post operatively in dogs which had an intercostal block with bupivacaine, but was seen at 16 h post-operatively when it could be anticipated that the effects of bupivacaine would have waned. These results suggest that intercostal block with bupivacaine can provide analgesia for over 8 h, and that the duration of action of nalbuphine in controlling post-operative pain in the dog is probably less than 4 h. PMID- 1753692 TI - Endocrine stress response in rats subjected to singular orbital puncture while under diethyl-ether anaesthesia. AB - In an attempt to assess possible discomfort in rats subjected to orbital puncture while under diethyl-ether anaesthesia, their endocrine stress response was determined. Concentrations of corticosterone, adrenaline and noradrenaline were measured in plasma obtained via a jugular catheter from rats subjected to diethyl ether anaesthesia with or without orbital puncture. No statistically significant differences were found between the punctured and non-punctured rats as to peak levels of plasma corticosterone and adrenaline as well as for the times required by the increased concentrations to return to baseline values. The rate by which the plasma noradrenaline level returned to baseline values was somewhat decreased by orbital puncture. Diethyl-ether anaesthesia alone produced a marked endocrine response when compared with handling and novelty stress associated with the induction of anaesthesia. It is concluded that diethyl-ether anaesthesia causes pronounced increases in the plasma levels of the selected stress hormones and that orbital puncture does not amplify this response. It is suggested that diethyl-ether anaesthesia masks any effects of orbital puncture. PMID- 1753693 TI - Vitamin D, within its range of fluctuation in commercial rat diets, does not influence nephrocalcinogenesis in female rats. AB - Massive, toxic doses of vitamin D have been shown to cause nephrocalcinosis in rats, but the effect of this vitamin within its range of fluctuation in commercial rat diets was unknown. Therefore, in two experiments with young female rats, the effect on nephrocalcinosis of a moderately increased level of vitamin D in the diet was studied, that is 5000 IU/kg versus the recommended concentration of 1000 IU/kg. This was done using purified diets with 0.5% (w/w) calcium and 0.04% magnesium containing either 0.2 or 0.6% phosphorus (P). Rats fed the diets containing 0.6% P showed severe kidney calcification compared to those fed the 0.2%-P diets. The level of vitamin D in the 0.2 and 0.6%-P diets did not affect kidney calcification. Bone density was increased after feeding diets containing 5000 instead of 1000 IU of vitamin D/kg. This study suggests that, within 28 days, a moderate increase of the amount of vitamin D in the diet has no influence on the development of kidney calcification. This in turn suggests that the variation in nephrocalcinosis severity and incidence seen in practice in rats fed different commercial diets is unlikely to be related to the different vitamin D concentrations in these diets. However, in rats fed such diets bone metabolism may be influenced differently. PMID- 1753694 TI - Pathogenicity of Pasteurella multocida A:3 in Flemish giant and New Zealand white rabbits. AB - Pasteurella multocida A:3 was isolated during an outbreak of pasteurellosis in Flemish Giant (FG) rabbits. Since New Zealand White (NZW) rabbits housed in the same room were not as severely affected as FG rabbits, experimental inoculation was undertaken to determine if FG rabbits were more susceptible than NZW rabbits to pasteurellosis induced by this isolate. Rabbits of each breed were inoculated with P. multocida A:3 and observed for 3 weeks. Four of 5 FG rabbits developed severe clinical disease on days 6, 9, 12 and 14 after inoculation; whereas, the one affected NZW rabbit became ill 14 days after inoculation. All rabbits with clinical disease developed fibrinosuppurative pleuritis, pyothorax and pneumonia which was more severe in FG than NZW rabbits. At necropsy, P. multocida A:3 was isolated from multiple sites of the diseased rabbits. No significant difference (P = 0.099) in the prevalence of lesions between the two breeds was found; however, the score of pneumonia and pleuritis was 3 times greater in FG rabbits than NZW rabbits. PMID- 1753695 TI - Toxicity of anticancer agents, growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice. AB - An investigation of the usefulness of a segregating stock of nude mice [AF nude mice (AF-nu)] for screening anticancer agents was undertaken. The toxicity of anticancer agents, takes and growth rates of human tumour xenografts and chemosensitivities of xenografts in AF-nu were studied and compared with those in BALB/cA nude mice (BALB/cA-nu). The results showed differences in the pattern of mortalities of AF-nu and BALB/cA-nu administered a range of anticancer agents. Body weight changes in the two nude mouse strains differed in the case of 5 fluorouracil, but not for nimustine, adriamycin and vincristine. All tumours transplanted in AF-nu grew as in BALB/cA-nu. Growth rates of 2 xenografts (gastric cancer and glioblastoma) were not significantly different between the 2 nude mouse strains, but those of 2 lung tumour xenografts were significantly greater in AF-nu than those in BALB/cA-nu. There were no significant differences in chemosensitivities of human tumours in AF-nu and BALB/cA-nu (consistency rate as evaluated by our criteria was 88%). From these results, it is suggested that AF-nu are more suitable for anticancer agent screening and experimental chemotherapy of human tumour xenografts than BALB/cA-nu because of lower costs and high reproductive rate. Although they are genetically heterogeneous, sets of experimental animals sharing the same gene pool can be produced routinely. PMID- 1753696 TI - The isolated, buffer-perfused ferret heart: a new model for the study of cardiac physiology and metabolism. AB - The isolated, buffer-perfused ferret heart is a new model for the study of cardiac physiology and metabolism. Compared to the more commonly used isolated heart preparation, the rat heart, the ferret has a lower rate-pressure product due to lower heart rate, a remarkably low coronary flow and almost complete oxygen extraction. The ferret heart remains in stable haemodynamic and metabolic conditions for a longer period of time than the rat heart. ATP contents of the two species are similar, but creatine phosphate content is higher in the ferret while NAD content is much lower. PMID- 1753697 TI - In-vivo monitoring of corticomedullary nephrocalcinosis in rats using computerized tomography. AB - An in-vivo method, computerized tomography (CT), was used to monitor nephrocalcinosis in female rats. CT density data correlated well with renal Ca content measured by atomic absorption spectrophotometry. In-vivo CT measurements revealed that the severity of nephrocalcinosis may change spontaneously with time. Manifest calcifications may exhibit spontaneous regression and are probably affected positively by high dietary Mg, in contrast to increased Ca. It is concluded that CT is a suitable and reliable non-invasive in vivo method to follow up time-dependent alterations in kidney calcifications in rats. PMID- 1753698 TI - Effects of pentobarbital and ketamine-xylazine anaesthesia on somatosensory, brainstem auditory and peripheral sensory-motor responses in the rat. AB - Somatosensory, brainstem auditory evoked and peripheral sensory-motor responses were recorded in rats anaesthetized with either pentobarbital or a ketamine xylazine combination. This was carried out in order to assess which of these agents degraded responses to a lesser extent and thus would be more suitable for monitoring experimental effects. Neither of the anaesthetic agents affected peripheral sensory or motor conduction, nor were there any interpeak latency changes of the early components of the brainstem auditory response. However, pentobarbital anaesthesia resulted in an increase in latency of the initial positive component of the somatosensory cortical evoked potential and attenuation of the following negative component. During the recovery stages of ketamine xylazine anaesthesia the longer latency evoked potential components were observed to emerge. PMID- 1753699 TI - Multifunctional roles for transforming growth factor-beta 1. PMID- 1753700 TI - Biology of aging: facts, thoughts, and experimental approaches. PMID- 1753701 TI - Expression of transforming growth factor-beta 1 during chemical hepatocarcinogenesis in the rat. AB - Cellular distribution of both transcripts and protein of transforming growth factor (TGF)-beta 1 was studied in preneoplastic nodules (6 cases) and primary hepatic carcinomas (16 hepatocellular carcinomas and 2 mixed tumors of hepatocellular carcinoma and cholangiocellular carcinoma) produced by Solt Farber's protocol in rats using in situ hybridization and immunohistochemistry. The TGF-beta 1 transcripts were primarily observed in nonparenchymal cells, some of which were desmin-positive perisinusoidal cells, surrounding or within the preneoplastic nodules or carcinomas. The distribution of latent TGF-beta 1 protein was similar to the transcripts. However, mature TGF-beta 1, which was identified with CC-antibody, was only detected in nonparenchymal cells and connective tissue associated with carcinomas, but was not observed in preneoplastic nodules or in normal liver with the exception of the periportal space. There was no difference in TGF-beta 1 expression associated with tumor types or the differentiation status of primary hepatic carcinomas. The present study demonstrates that nonparenchymal cells, particularly desmin-positive perisinusoidal cells, are the principal source of TGF-beta 1 production during hepatocarcinogenesis. Furthermore, the data suggest that the close interaction between nonparenchymal cells and carcinoma cells may be necessary for the activation of latent TGF-beta 1. It is hypothesized that regulatory effects of TGF-beta 1 on growth of preneoplastic or carcinoma cells in the liver are exerted via paracrine mechanism. PMID- 1753702 TI - Role of beta 1 integrins in tumor cell adhesion to cultured human endothelial cells. AB - We investigated the effects of beta 1 integrins on tumor cell (TC) adhesion to unstimulated and interleukin-1 (IL-1) activated endothelial cells (EC). IL-1 treatment (20 units/ml for 6 hours) of cultured human umbilical vein EC significantly increased adhesion of seven human TC lines of different origin. A goat antiserum raised to purified alpha 5 beta 1 integrin abolished the IL-1 induced increment in adhesion of two osteosarcomas, one melanoma, one lung, and one kidney carcinoma, whereas it did not affect adhesion of two colon carcinoma cell lines. Further studies were performed on MG63 osteosarcoma cells. Adhesion of MG63 osteosarcoma cells to EC was dependent on time of EC treatment with IL-1: it was maximal at 12 hours and declined at 24 hours. alpha 5 beta 1 antiserum blocked IL-1 induced increase in MG63 adhesion at any time of EC treatment. This effect appears to be mainly directed to MG63 integrins since selective incubation of the antiserum with EC, but not with MG63, did not modify TC adhesion. Using a series of antibodies to different alpha and beta chains, we found that only monoclonal antibodies (mAb) to alpha 4, alpha 5, and beta 1 could inhibit MG63 adhesion to IL-1 activated EC, whereas alpha 2, alpha 6, and beta 3 antibodies were ineffective. Antibodies to fibronectin had very little activity on MG63 adhesion to EC matrix and did not significantly affect MG63 adhesion to control or IL-1 treated EC. Antibodies to alpha 4, alpha 5, and beta 1 were only partially effective in inhibiting MG63 adhesion to EC matrix. These data indicate that the capacity of alpha 4 beta 1 and alpha 5 beta 1 integrins to bind fibronectin contributed very little to MG63 adhesion to EC. The importance of beta 1 integrins in promoting a direct interaction between EC and MG63 was further shown by inhibition of rosette formation among these cells in suspension by the alpha 5 beta 1 antiserum. Only a VCAM-1/INCAM110 mAb, but not ELAM-1 or ICAM-1 mAbs, could inhibit MG63 adhesion to IL-1 activated EC. Overall these data indicate that at least two members of the beta 1 integrin subfamily (alpha 4 beta 1 and alpha 5 beta 1) are involved in MG63 adhesion to cytokine treated EC. This integrin function might be important at early stages of TC interaction with the vessel wall. PMID- 1753703 TI - Cellular infiltrate, major histocompatibility antigen expression and immunopathogenic mechanisms in cardiac myosin-induced myocarditis. AB - Immunization with cardiac myosin induces severe myocarditis in genetically predisposed mice. The disease closely parallels that seen after infection with Coxsackievirus B3 and is characterized by a diffuse interstitial cellular infiltrate. To analyze the immunopathologic events in the heart tissue of cardiac myosin-immunized A/J and A.SW mice, the phenotype of inflammatory cells and the expression of class I and class II major histocompatibility (MHC) antigens (Ag) was examined at different time points using the immunoperoxidase method. On day 14 after the initial immunization, very few inflammatory cells were seen, whereas on day 21 the lesions were severe and extended over the whole ventricular wall. At both time points tested, the inflammatory infiltrate was composed of Mac-1+ cells, representing 70 to 80% of the infiltrate, and Thy-1.2+ cells, representing 20 to 25%. These Thy-1.2+ cells consisted of CD4+ cells and to a lesser extent of CD8+ cells. Essentially, no B cells were found on day 14, and on day 21 their frequency was only 1 to 2%. Furthermore, massive Ig deposits were observed along the infiltrated myofibers. Both on day 14 and 21, MHC class II Ag expression was associated with cells of the inflammatory infiltrate, but no aberrant I-A Ag expression was found on endothelial cells of coronary vessels or on myofibers. Similarly, no increased MHC class I Ag expression was seen on myofibers on day 14. However, on day 21 the infiltrated myofibers did show an increase in surface MHC class I Ag expression, thereby suggesting that this phenomenon is a consequence of the inflammatory process. Furthermore, in vivo administration of monoclonal antibodies to either CD4 or CD8 protected cardiac myosin-immunized mice from myocarditis, and a similar effect was achieved by monoclonal antibody to I-A Ag. Thus, cardiac myosin-induced myocarditis is mediated by a cooperation between CD8+ cells and MHC class II restricted, i.e., CD4+ cells. PMID- 1753704 TI - Rat glomerular cells do not express podocytic markers when cultured in vitro. AB - A panel of cell-type specific monoclonal and polyclonal antibodies and lectins was used to examine the early, morphologically epithelial outgrowth of rat renal glomerular cells in culture. The cell type-specific reactivity of the monoclonal antibodies has been previously verified on tissue sections of rat kidneys at light and electron microscopic levels. Morphologically distinct epithelial cells grew out from the isolated glomeruli within 3 days in culture, followed by the growth of morphologically typical stellate mesangial-like cells. Endothelial and mesangial cells were positively identified from the early cultures (up to 10 days) with antibodies to a 350 kD protein, dipeptidyl peptidase IV, podocalyxin, factor VIII, OX-43 and with Bandeiraea simplicifolia (BS-I B4) lectin, and with antibodies to smooth muscle actin, desmin, Thy1.1 antigens and with Ricinus communis (RCA-1) lectin, respectively. The antibodies recognizing podocytes in vivo (antipodocalyxin, anti-O-acetyl GD3 ganglioside, anti-gp330, anti-C3b complement receptor, anti-vimentin and anti-CALLA) consistently failed to bind to the predominant epithelial cells in early cultures, although these antibodies readily bound to the cells of the intact glomeruli remaining in culture. The attempts to augment the expression of cell-type specific epitopes by culturing glomeruli on various matrices or by enriching the medium with various growth factors, failed to induce podocytic epitopes on the growing epithelial cells. Glomeruli from newborn rats cultured in vitro, but were also constantly negative for the markers of podocytes. In addition, we cultured glomerular-like bodies from in vitro were induced metanephric mesenchymes but failed to obtain evidence of growing podocytes. However, the epithelial cells reacted with antibodies to thrombospondin and cytokeratin that react with the parietal epithelium of glomeruli on tissue sections. The results show that early glomerular cultures consist of mesangial, endothelial and presumably parietal epithelial cells readily identifiable by immunocytochemical methods. No podocytes could be grown under the various growth conditions tested. This suggests that glomerular podocytes are effectively growth arrested and call for new approaches to obtain these cells in culture. PMID- 1753705 TI - Atubular glomeruli in renal artery stenosis. AB - The aim of the present study was to investigate and quantitate the structural renal changes developing after stenosis of the renal artery. Twelve kidneys removed at operation from patients with elevated blood pressure due to stenosis of the renal artery were investigated together with three kidneys with renal artery stenosis but no clinical evidence of renovascular hypertension. Eight age matched autopsy kidneys served as controls. Stereologic methods were used to estimate the volume fractions of different structural parameters, the volume of individual glomeruli, and the structural integrity between the glomerulus and the proximal tubule. In six of the kidneys with renal artery stenosis and in the controls, the total number of nonoccluded glomeruli was estimated. Immunohistochemical staining for epithelial membrane antigen, Tamm-Horsfall protein and lectin Arachis hypogaea was performed in order to determine whether the atrophic tubules in renal artery stenosis were of proximal or distal origin. The results showed that the volume fractions of both proximal and distal tubules had decreased in renal artery stenosis, whereas the volume fractions of the glomerular tufts and interstitium increased. Immunohistochemical staining indicated, however, that more distal than proximal tubules were preserved, although atrophic. In the kidneys with artery stenosis, very few glomeruli were seen connected to a normal proximal tubule; in 52% of the glomeruli Bowman's capsule did not open toward a tubule and 40% were connected to an atrophic tubule. The mean glomerular volume (uncorrected for shrinkage) of 1.5.10(6) microns3 in the kidneys with artery stenosis was significantly decreased compared with the 2.9.10(6) microns3 in the controls. The mean glomerular number was normal in the kidneys with artery stenosis. The study shows that despite the absence or severe atrophy of the tubules, the glomeruli are not destroyed but only smaller. More proximal than distal tubules are destroyed by the ischemic process. PMID- 1753706 TI - Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog. AB - Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period. PMID- 1753707 TI - Glomerulosclerosis at both early and late stages is associated with increased cell turnover in mice transgenic for growth hormone. AB - The evolution of glomerulosclerosis consists of a progressive increase in mesangial matrix with gradual glomerular obliteration. The sclerotic process is thought to be irreversible and include a progressive loss of glomerular cells. To investigate this process, we selected mice transgenic for bovine growth hormone because they develop progressive glomerulosclerosis and renal failure. The sequence of histologic events in the growth hormone mice consists initially of an increase in the number of centrolobular glomerular cells, followed by an accumulation of extracellular matrix. This is accompanied by an increase in glomerular size which is disproportionate to the overall increment in kidney or body weight. The [3H]thymidine labeling index of the cells of the glomerular tuft was assessed before the development of recognizable sclerosis and at a time when the sclerosis was far advanced. The labeling index was more than five-fold increased over controls at the early time point. Contrary to what was expected, the labeling index remained at the same high levels in densely sclerotic glomeruli at the late time point. In conclusion, increased cell turnover is a significant component of the sclerotic process both at the onset and in the late stages of this model. PMID- 1753708 TI - Regulation of mRNA stability and its relevance to disease. PMID- 1753709 TI - Arthritis in rhesus monkeys experimentally infected with simian immunodeficiency virus (SIV/DELTA). AB - The joint tissues from 36 rhesus (age 2-5 years) infected with SIV/Delta were graded into four groups and then correlated with the following systemic immunologic parameters: numbers of CD4+, CD4+ plus CD29+, and CD20+ cells and SIV/Delta antigenemia. Grade I (n = 16) consisted of normal synovial membrane; grade II (n = 8) consisted of synovial hyperplasia; grade III (n = 8) consisted of a mononuclear cell infiltrate, and grade IV (n = 4) consisted of synovial membrane infiltration of syncytial cell and mononuclear type cells. Synovial membranes from 20 uninfected age-matched rhesus were compared with infected animals and were graded 1. Immunostaining of the tissue phase lymphocytes and viral antigen was performed using monoclonal antibodies commercially available and a monoclonal antibody produced against a core protein of the SIV/Delta agent. SIV/Delta infection resulted in a reduction in cells doubly stained for CD4+ and CD29+ and a relative increase in CD8+ stained cells. A significant (ANOVA) difference was not observed in CD4+, CD4+ plus CD29+, CD8+, or CD20+ among the various grades of arthritis. Viral antigen was demonstrated in syncytial cells of the grade IV reaction. This finding suggests that the SIV/Delta arthritis is a primary viral reaction. PMID- 1753710 TI - Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6. AB - Liver fat-storing cells (FSC) play an important role in collagen deposition. During the induction of liver cirrhosis, FSC lose their fat droplets, acquire an actin-rich cytoskeleton and transform into myofibroblasts. Myofibroblasts have been associated with increased collagen production in cirrhotic livers. Cultured FSC resemble myofibroblasts. However, it is not known whether regulation of collagen gene expression is similar in FSC obtained from normal or cirrhotic livers. In this communication, we describe the characterization of two fat storing cell lines, one from normal (NFSC) and one from CCl4-cirrhotic liver (CFSC), obtained after spontaneous immortalization in culture. We studied the effect of serum and various growth factors on cell proliferation. We determined the production of collagen and fibronectin and we analyzed the presence of mRNA transcripts of collagens type I, III, and IV, fibronectin laminin, transforming growth factor-beta and interleukin-6. We found that CFSC have a greater serum dependency than NFSC. NFSC grow with a mixture of insulin and epidermal growth factor, whereas CFSC proliferate only with platelet-derived growth factor. Although we did not find significant differences in the expression of mRNAs for collagen type I, fibronectin and transforming growth factor-beta, collagen and fibronectin synthesis was increased 2- and 1.5-fold respectively. NFSC contained 1.6- and 2.0-fold more type III collagen and laminin mRNAs, respectively, than CFSC. Neither cell line expressed type IV collagen mRNA. NFSC but not CFSC produced interleukin-6. These results suggest that, except for the lack of transcripts of collagen type IV, both cell lines resemble primary cultures of FSC. However, significant differences in cell proliferation and interleukin-6 production between the two cell lines were found. We suggest that these cell lines could be useful tools to study possible differences in regulation of matrix production by FSC. PMID- 1753711 TI - Hepatocytes modulate the hepatic microvascular phenotype. AB - The liver microvasculature is unique among epithelial organs because it is composed of sinusoids rather than capillaries. Since hepatocytes lack a basement membrane, they are not separated from plasma by any continuous filtration barrier. During the cirrhotic process, the sinusoids become transformed into typical continuous capillaries with specialized endothelial junctions, continuous basement membrane, and pericytes. To explore the factors that determine the phenotype of the hepatic microvasculature, we implanted fetal rat liver fragments onto the chorioallantoid membrane of 6-day-old, shell-less, quail embryos. After 5 days in culture they were studied by light and electron microscopy immunohistochemistry using markers specific for: quail cells, hepatocytes, and basement membrane components of murine or avian origin. The normal quail chorioallantoid membrane is vascularized by continuous capillaries. The periphery of the transplanted fetal rat liver fragments becomes vascularized by microvessels of quail origin. However, the quail microvessels in the proximity of rat hepatocytes assume a sinusoidal phenotype with fenestrations lacking diaphragms, endothelial cell gaps, and devoid of basement membrane. These results demonstrate that liver cells modulate the phenotype of the hepatic microvascular. Since hepatocytes and endothelium do not establish direct cell contacts, we postulate that this modulation is exerted either by secreted soluble cytokines or by the extracellular matrix. PMID- 1753712 TI - Amino acid protection of cultured kidney tubule cells against calcium ionophore induced lethal cell injury. AB - Treatment of two cultured renal tubule epithelial cell lines, MDCK and LLC-PK1, with ionomycin produced rapidly evolving models of lethal cell injury characterized by increases of cytosolic free calcium to the microM level within 15 minutes followed by lactate dehydrogenase release and failure to exclude vital dyes that began between 30 and 60 minutes and became extensive after 60 minutes. The pattern of injury was similar when the mitochondrial uncoupler, carbonyl cyanide-m-chlorophenylhydrazone, was added to ionomycin. Carbonyl cyanide-m chlorophenylhydrazone alone produced severe ATP depletion but not lactate dehydrogenase release. Inclusion of glycine in the experimental medium at concentrations ranging from 0.25 mM to 5 mM did not affect the increases of cytosolic free calcium or ATP depletion but was protective against enzyme release and failure to exclude vital dyes for 180 minutes. Maximal protection was achieved at glycine concentrations between 1 and 5 mM. Several other small neutral amino acids including alanine, beta-alanine, L-serine, 1 aminocyclopropane-1-carboxylic acid, and alpha-aminoisobutyric acid also had protective effects but, glucose, pyruvate, glutamate, glutamine, leucine, valine, and taurine did not. These data indicate that potent protective effects of glycine and other small neutral amino acids previously shown in fresh tubule preparations are fully expressed in cultured tubule cells of diverse origin when appropriate acute injury models are used and the protective effects are sustained for long durations. The suitability of cultured cell lines for prolonged exposure studies will provide a powerful way of further exploring mechanisms of these effects. PMID- 1753713 TI - Decreased prolactin level in secretory granules and their increased exocytosis in estrogen-induced pituitary hyperplasia in rats treated with a dopamine agonist. AB - Treatment with bromocriptine (CB) stimulates the release of secretory granules from human prolactinomas by exocytosis in spite of a remarkable decrease in serum prolactin (PRL) levels. In an attempt to elucidate the reasons for this phenomenon, secretory granules were analyzed in estrogen-induced pituitary hyperplasia in rats which served as a model of human disease. The amount of protein contained in cell fractions rich in secretory granules was the same in CB treated pituitaries as that in the controls, whereas PRL levels decreased to about a half the level of the controls. Morphometric analysis using point counting and electron immunocytochemistry revealed that the PRL concentrations in secretory granules decreased to about 50% after CB-treatment. Serum PRL levels estimated by counting the exocytotic secretory granules were remarkably lower in CB-treated rats than in the controls. It was suggested that the composition of secretory granules changed or that nonhormonal constituents in the granules disintegrated more slowly after CB treatment, thus allowing exocytosed granules to be observed more frequently. Additionally CB might also suppress a bypass release of PRL by which PRL is secreted without being packaged into secretory granules. PMID- 1753714 TI - Sialoadenitis in experimental graft-versus-host disease. An animal model of Sjogren's syndrome. AB - Using light microscopic, immunohistochemical, and ultrastructural techniques, we studied sialoadenitis in mice with chronic graft-versus-host disease (GVHD). To induce chronic GVHD, DBA/2 spleen cells were injected into nonirradiated (C57BL/6 x DBA/2)F1 mice. By light and electron microscopy, the submandibular gland lesion was characterized by mononuclear cell infiltration around the interlobular ducts, often with parenchymal destruction. Immunohistochemically, T cells predominated. The ratio of CD4+ to CD8+ T cells ranged from 1.9:1 to 6:1, with an average of 3.6:1. Lesser numbers of B cells, plasma cells, and macrophages were also present. Histologically, lymphocytic sialoadenitis in chronic GVHD mice was very similar to that reported in patients with chronic GVHD and Sjogren's syndrome. PMID- 1753715 TI - Development, characterization, and utilization of an intestinal xenograft model for infectious disease research. AB - Paired xenografts of near-term fetal rabbit jejunum were subcutaneously implanted in the backs of athymic nude (nu/nu) mice. At 3 to 4 weeks post-implantation, the grafts had histologic, ultrastructural, and biochemical (lactase, sucrase, alkaline phosphatase, leucine aminopeptidase) parameters comparable to age matched control rabbits. Four weeks post-transplantation the xenografts were intraluminally inoculated with various strains of lapine attaching and effacing E. coli or group A rotavirus. Infection with 2 strains of E. coli resulted in typical light microscopic and ultrastructural lesions of attachment and effacement. Immunohistochemical analysis of rotavirus-infected xenografts demonstrated rotavirus antigen within enterocytes. These lesions are comparable to those in conventional rabbits. Intestinal xenografts are a novel, highly controlled, and reproducible model which may have unique applications in the study of enteric diseases. The model provides anatomically and biochemically correct intestinal mucosal epithelium uncomplicated by variables such as enteric flora, host immune response, gastric, hepatic, and pancreatic secretions and is susceptible to infection by specific enteropathogens. Xenografts, therefore, may be a viable alternative in certain investigations where whole animals, ligated intestinal loops, organ cultures, or cell cultures might otherwise be chosen. PMID- 1753716 TI - Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. AB - To examine the mechanism of mitochondrial myocytotoxicity caused by long-term administration of zidovudine (AZT) in human immunodeficiency virus-positive patients, we examined the effect of AZT in vitro on human muscle in tissue culture and in vivo in rats treated with daily intraperitoneal injections of AZT at doses equivalent to the total daily dose used in acquired immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in tissue culture exhibited abnormal mitochondria characterized by proliferation (mean +/- SD, 27.5 +/- 8 mitochondria/16 microns2 surface area, compared with 12.8 +/- 4 in the control cultures (p less than 0.001], enlarged size, abnormal cristae and electron-dense deposits in their matrix. The changes were partially reversible after AZT withdrawal. Rats treated with AZT developed weight loss, 100-fold elevation of creatine kinase, and increased serum lactate and glucose. In tissues, AZT had its highest concentration in the skeletal muscle and the heart. Skeletal and heart muscles from the treated animals, but not the controls, showed enlarged mitochondria with disorganized or absent cristae and electron-dense deposits in their matrix. Study of the mitochondrial functions assessed by evaluating stimulated oxygen consumption rate, enzymatic activities of electron transport chain and coupling state of oxidative phosphorylation (respiratory control ratio) revealed a decrease in rotenone-sensitive NADH cytochrome C reductase (complex I + III) and an uncoupling effect demonstrated by decreased respiratory control ratio. We conclude that AZT, a DNA chain terminator, is a muscle mitochondrial toxin that affects the oxidation-phosphorylation coupling and the activity of complex I and III of the mitochondrial respiratory chain. PMID- 1753717 TI - Relationships of structural dimensions to bench press strength in college males. AB - The purpose of this study was to determine the relationships between structural dimensions and bench press performance in college males. Members of required fitness classes (n = 170) were measured after 14 weeks of strength and aerobic endurance training. Anthropometric dimensions included upper arm and chest circumferences, upper and lower arm lengths, shoulder and hip widths, %fat, and height. Arm muscle cross-sectional area (CSA) was calculated from upper arm circumference corrected for triceps skinfold. Drop distance was measured from the bar to the pectoral muscles. Multiple regression analysis selected upper arm CSA, %fat, and chest circumference as the best items to predict bench press strength (R = 0.83; SEE = 11.6 kg). Cross-validation of the prediction equation on a similar sample (n = 89) produced an r = 0.74 between predicted and actual bench press (t = 0.53, p greater than 0.50). In a second cross validation sample (n = 57) who had trained more extensively with weights, the correlation between predicted and actual bench press was r = 0.57 (p less than 0.05). The prediction equations significantly (t = 6.59, p less than 0.01) underestimated bench press performance in the more extensively weight trained subjects. The results of this study suggest that bench press performance is related to structural dimensions in males and that extensive strength training may alter the relationship between size and strength. PMID- 1753719 TI - Influence of two levels of caffeine on maximal torque at selected angular velocities. AB - The purpose of this study was to determine the effect of two doses of caffeine on peak torque and muscle endurance in the knee extensors and flexors. Twenty males and 16 females were randomly assigned to one of three groups: 600 mg caffeine, 300 mg caffeine, or a control receiving a placebo. Subjects with similar caffeine consumption history were used and all subjects abstained from caffeine usage for 24 hours prior to testing. Subjects were tested for maximal strength and endurance at 75, 180, and 300 degrees per second using a Cybex II Isokinetic Dynomometer interfaced with a Cybex Data Reduction Computer. After pretesting, each subject was given one of three solutions using a double-blind design. Following a one hour rest and absorption period, the subjects were again tested. Data were analyzed using a 3 x 2 repeated measures analysis of variance with a grouping factor at three levels (600 mg vs 300 mg vs 0 mg) and a trial factor at two levels (pre- vs posttest). The following variables were analyzed at all angular velocities: peak torque and subsequent joint angle, peak torque at 30 degrees, and peak torque at 70 degrees. At 300 degrees per second, the dependent variables were total torque for 15 repetitions, total torque for the first 3 repetitions, and total torque for the last 3 repetitions. The results indicated no significant changes from pre- to posttest. It was concluded that maximal strength and endurance was not affected by the two levels of caffeine used in this study and that caffeine may not be considered an ergogenic aid in strength output in subjects naive to resistance training. PMID- 1753718 TI - Serum thyroid hormones, thyrotropin and thyroxine binding globulin in elite athletes during very intense strength training of one week. AB - The effects of a one-week very intense strength training period on maximal strength and pituitary-thyroid function were investigated in eight elite male weight lifters. No statistically significant changes occurred in the maximal isometric leg extension force of the test subjects. Decreased serum concentrations of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) were found during the training period, but no statistically significant changes occurred in the levels of free thyroxine (fT4), reverse T3 (rT3) and thyroxine binding globulin (TBG). The results suggest that the training stress affects at the hypophyseal and/or hypothalamic level decreasing the secretion of TSH, which leads to slightly decreased function of the thyroid gland. PMID- 1753720 TI - Weight training economy as a function of intensity of the squat and overhead press exercise. AB - The purpose of this investigation was to study the relationship between exercise intensity and weight training economy. Seven subjects performed squat and seated behind the neck press exercises at 60% and 80% of one repetition maximum (1 RM). Addition of net exercise oxygen uptake (VO2) to net recovery VO2 provided an estimate of metabolic cost for the exercise. Estimation of work performed was accomplished by calculation of vertical external work (VEW). Weight training economy was calculated (weight training economy = kcals consumed x VEW-1). The squat was significantly more economical than the overhead press (p = 0.002), and exercise at 60% 1 RM was more economical than exercise at 80% 1 RM (p less than 0.001). Correlations between VEW and kcals consumed at each intensity ranged between 0.85-0.98. It was determined that estimation of metabolic cost of weight training exercise must take into account not only the vertical external work accomplished, but also the intensity of the exercise (% 1 RM). Vertical external work performed on the bar appears to be as accurate as the total vertical external work value in prediction of metabolic cost of the squat and overhead press exercises. Use of the weight training economy values obtained in this study for prediction of metabolic cost will provide values with 4.2%-15.8% prediction error. PMID- 1753721 TI - Determination of player potential in volleyball: coaches' rating versus game performance. AB - The purpose of this study was to determine if the factors which coaches feel indicated superior player potential were the same as those factors which contribute to successful competition outcome. Players from two colleges were evaluated for general and specific performance variables prior to a regular season match between the teams. A player's ability rating was the total of four coaches' ranking on a 1-to-10 scale. Multiple regression analysis to predict player ability rating selected age, vertical jump, total body movement time, and agility (R = 0.87). However, step-wise discriminant analysis to differentiate winning and losing team members selected shoulder flexibility, agility, forearm bump, and sit-and-reach flexibility. The canonical correlation between the winning-losing dichotomy and these skills was 0.74 and resulted in proper classification of 84.6% of the correct team members. It was concluded that the skills coaches consider indicative of superior ability are not necessarily the factors which dictate winning performance. PMID- 1753722 TI - The structural, functional, and nutritional adaptation of college basketball players over a season. AB - The purpose of this study was to determine the structural, functional and nutritional adaptation of college basketball players over a season. Structure was determined by somatotype and body composition, function was determined by peak work capacity and work efficiency, and nutrition was determined by plasma metals analysis. The tests were performed twice on each of the eight subjects, one preseason (PRS) and one postseason (PST). A small structural adaptation was indicated by a mean decrease (less than 1 kg) in fat free weight and an increase in ectomorphy (less than 0.03). Body weight and skinfolds did not change significantly. Functional adaptation was indicated by a one minute decrease in running time for the work capacity test (p less than 0.002), and an increase (p less than 0.02) in VO2 for the work efficiency test. Nutritional adaptation was indicated by a greater mobilization of plasma Zn after exercise during PST than PRS. Plasma Cu apparently was mobilized during exercise in PST but the change during the season (-10 to -6.6%) was not statistically significant because of the large interindividual variability in response. Structural and functional adaptation to basketball training over a collegiate season is small; however, the change in Zn mobility and the tendency for a concomitant change in Cu mobilization offers a unique finding to help explain the nutritional adaptation to training. PMID- 1753723 TI - Anthropometric, body composition and performance variables of young elite female basketball players. AB - The purpose of the study was to determine the physique and body composition of young female basketball players and to examine these variables in relation to their playing position. Eighteen members of the under seventeen England Basketball squad were measured on twenty different anthropometric sites from which somatotype and body composition were calculated. Four performance measures, vertical jump, anaerobic power, right and left grip strength and laterality were also measured. The variables of the basketball players grouped according to playing position were then compared statistically using ANOVA. Centres had the largest measures of physique and body composition followed by the forwards and then the guards. These differences were significant, particularly between the centres and the guards. The centres were much taller, had longer limb lengths, hip widths and were more muscular. PMID- 1753724 TI - Body build and performance characteristics of male adolescent track and field athletes. AB - Body build and performance characteristics were studied in 38 elite young male track and field athletes. The athletes were classed into 4 groups depending on their chosen event: Sprinters/Hurdlers (SPR), Jumpers (JUMP), Throwers (THR) and middle distance runners (MD). Performance characteristics investigated were vertical jump (VJ), the Margaria stair run (MARG) and the Wingate Test (WING). Analysis of variance results showed THR to be significantly different from other groups in body build and MD to be significantly different from other groups in performance characteristics. Further investigation revealed that in the 4 groups studied, body weight and vertical jump height are 2 simple measures of differentiating between event participation. PMID- 1753725 TI - Long-term effects of a lifestyle modification exercise program on the fitness of sedentary, obese children. AB - We studied the effects of a lifestyle modification and exercise program on the fitness of 12 sedentary and obese children who were physician-referred into a 1 month YMCA lifestyle modification program. These variables were measured at entry, at the program's conclusion, and 1 and 4 months following conclusion: weight (lbs), sum of 2 skinfolds (mm), number of sit-ups, 9-minute run (total distance in yds), sit-and-reach for flexibility (cm). Total serum cholesterol (mg/dl) was measured only at entry and 4 months following conclusion. We found a NS decrease in weight (124 to 117 lbs) and sum of skinfolds (54 to 40 mm); a significant (p less than 0.01) increase in sit-ups (23 to 35); a significant (p less than 0.05) increase in 9 minute run distance (1201 to 1419 yds); no change in flexibility; and a NS decrease in total serum cholesterol (178 to 155 mg/dl). It was concluded that, while good changes were made, a longer period of time would be required to significantly reduce weight, sum of skinfolds, and total serum cholesterol. PMID- 1753726 TI - Effects of swimming and land exercises versus swimming and water exercises on body composition of college students. AB - The purpose of this study was to examine the effects of 2 different swimming and calisthenic exercise programs on body composition and swim performance. Subjects were forty-two students (M = 19; F = 23; mean age = 20.8 yr). The experimental groups (Swim-Land [SL], n = 14; Swim-Water, [SW], n = 16) participated in 35-40 min exercise sessions which consisted of a 5-10 min warm-up, 15-20 min of swimming, and 10-15 min of calisthenics three times per week for 8 weeks. The SL experimental group performed calisthenics on land with surgical tubing while the SW experimental group performed comparable calisthenics in the water. Subjects were pretested and posttested utilizing hydrostatic weighing to determine body density and calculate percent fat. Skinfold measures and the 12-min swim for distance were also measured. Results indicated a significant 20% increase in swim performance in both experimental groups (SL = 455 +/- 144 m to 553 +/- 114 m; SW = 465 +/- 122 m to 556 +/- 123 m; p less than 0.05) but no difference between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753727 TI - Specialized physical training programs: effects on serum lipoprotein cholesterol, apoproteins A-I and B and lipolytic enzyme activities. AB - To determine the effects of different types of physical training on lipid metabolism, serum lipids, lipoprotein cholesterol, apoproteins A-I and B, hepatic (HTGL), extrahepatic (LPL) and total (PHLA) post-heparin lipoprotein lipase activities were studied in elite athletes engaged in aerobic ("B", no. 13), anaerobic ("C", no. 17) and mixed ("D", no. 9) training programs and in a group of sedentary controls ("A", no. 15). In the aerobic and mixed groups serum triglycerides were significantly lower compared to sedentary controls while total serum cholesterol and LDL cholesterol, as well as serum apoprotein B levels were only slightly lower. HDL cholesterol and HDL2 cholesterol were slightly higher while serum cholesterol/HDL cholesterol (2.89 +/- 0.37 vs 3.6 +/- 0.47, p less than 0.01) and LDL cholesterol/HDL cholesterol (1.69 +/- 0.38 vs 2.23 +/- 0.43, p less than 0.05) ratios were significantly lower only in aerobic athletes compared to the control group. PHLA and LPL activities were slightly higher in the aerobic group than in controls, while PHLA and HTGL were significantly lower in aerobic and mixed athletes. No significant correlations were found between HDL cholesterol and energy expenditure during training, indexes of adipose mass or lipolytic enzyme activities. The results of this cross-sectional study seem to indicate that specialized training programs have a different effect on lipoprotein pattern and lipolytic enzyme activities, and only aerobic exercise has a potentially antiatherogenic effect. PMID- 1753728 TI - Effects of flexibility training on enhancing spinal mobility in older women. AB - The purpose of this study was to examine the extent to which spinal flexion and extension, or spinal mobility, could be improved in a population of older adults participating in a 10 week flexibility training program. Twenty female volunteers, mean age 71.8, were randomly assigned to either the experimental group (flexibility training) or the control group (no training). Prior to the initiation of training, all subjects were tested for total spinal mobility, the combined sum of spinal flexion and extension. Subjects in the experimental group were exposed to a series of flexibility exercises, three times per week, for 20 30 minutes in duration, for a total of 10 weeks. The control group participated in an alternative exercise program with the experimental group, including walking, swimming, dance, and other locomotor activities, however, they did not receive the additional flexibility training. At the conclusion of the 10 week period, all subjects were retested for spinal mobility, using back flexion and extension measures. Results indicated a significant improvement in spinal mobility in the experimental group, and virtually no measurable change in the control group. This study suggests that specialized training in back flexibility for older adults is warranted, and that significant gains in spinal mobility can be obtained, regardless of age. PMID- 1753729 TI - Former athletes physical fitness. AB - Genetic and environmental factors determine man's physical fitness. To the environmental factors exerting an active influence on the human organism belong intensive motoric exercises in the form of sport. With the passing of time there occur involutive structural and functional changes in man's organism. In order to determine the degree past sport activities shaped involution processes, a series of anthropometric and efficiency studies of 169 former sportsmen and randomly chosen men aged 39-73 were carried out in 1973; these studies were repeated ten years later (in 1983). It appeared that there existed substantial differences between former sportsmen and control groups (1973). In some physical efficiency tests these differences amounted to 15-20 years to the advantage of sportsmen. Studies repeated in 1983 allowed to assess the dynamics of involution changes appearing in the two groups-chiefly in the sphere of movement. The studies indicated that the motor regress began among the sportsmen not only at a higher level of original physical efficiency but its progress was slower. PMID- 1753730 TI - Biomechanical vibration of the abdominal region during running and bicycling. AB - The incidence of gastrointestinal (GI) distress reported among long distance runners and not in practitioners of other sports with more gliding movements, such as bicycling, leads one to speculate that there is a difference in concussions and vibration of the GI region and that this may possibly be associated with the disparity in GI disorders. The present experiment was conducted to quantify the difference in vibration (accelerations/decelerations) of the GI region during running as compared to bicycling. An actometer was used which included a piezoelectric sensor. The sensor was placed on the abdomen of six subjects during identical trials of bicycling and running. Movement in three planes was detected by the sensor and recorded. The accelerometer output (AO) is an integral of these measurements. AO was used in making comparisons of the two types of movement, expressed as counts per minute. Mean AO was more than doubled in running, 859.5 +/- 130.1 (SD), versus bicycling, 425.8 +/- 149.5 (SD) (p less than .0001). The common assumption that running results in more body vibrations than bicycling has been substantiated and quantified. Although the differences are large, it can only be speculated that these differences explain the high frequency of GI symptoms among runners. PMID- 1753731 TI - Assessment of static balance in children. AB - The ability in maintaining body balance of 6-, 8-, and 10-year-old children performing three balance tests on a force platform was studied. Thirty adult subjects served as a reference group. The mean radius (MR) of the posturogram and the mean speed (MS) of the center of foot pressure (COP) were used as the measuring parameters. Data were analyzed using two-way ANOVA, the Sheffe test and the Student "t" test with a .05 level of significance. A decrease with age in both mean radius and mean speed, indicating an increase in balance ability, was noted. A significant age main effect was found on all tests while significant gender main effect occurred only on the Tandem test. No significant age/sex interaction was found. Significant differences between the 10-year-old and adult groups occurred only in the more difficult balance tests. PMID- 1753732 TI - Acute recovery profile of lung volumes and function after running 5 miles. AB - The purpose of this study was to characterize the acute changes and recovery profile of lung volumes and function subsequent to strenuous aerobic exercise. Eight experienced runners (X age = 25 yrs; wt = 73 kg; ht = 181 cm) completed three identical 5 mile runs. Determinations were made of forced vital capacity (FVC), residual volume (RV), closing capacity (CC), and pulmonary diffusion capacity (DLCO). Measurement of cardiac output (Q) and stroke volume (SV) occurred simultaneously with the 10 second DLCO breathhold maneuver. Measurements were obtained before and 5, 15 and 25 minutes after each run. FVC was reduced ( 4.5%) 5 min post-run with a return to pre-run values by 15 min. CC (+16%) and RV (+18%) remained elevated for at least 30 min post-run. DLCO did not appear to be effected by the run. However, the single-breath DLCO breathhold maneuver consistently caused a fall in SV at rest and during recovery. The hypothesis has been forwarded that an increase in central blood volume post-run accounted for the acute reduction in FVC. The sustained elevation in RV resulted from early closure of the small airways possibly due to an increase in extra-vascular lung water. PMID- 1753733 TI - Effects of venous return on respiratory response. AB - This study reevaluated the link between the rate of CO2 flow to the pulmonary circulation and changes in cardiac output to the respiratory responses following leg lifting in normal man subjects. Thirty healthy subjects (mean age = 22.2 years) were subjected to the experimental maneuver which increased venous return to the right heart. Cardiac output was significantly increased and with it a significant increase in CO2 output by the lungs was found. These results were associated with a significant increase in expired ventilation. The rapidity of the ventilatory response to the increase in cardiac output suggests the existence of pressoreceptors localized in the pulmonary circulation which, when activated, results in the elicitation of respiratory reflexes. The end result is an adjustment in the respiratory response in accordance with venous return. PMID- 1753734 TI - Effects of respiration on size and function of the athletic heart. AB - This study compares the effects of quiet breathing on the heart structure and function of pentathlon athletes (n = 11) and a less-conditioned control group (n = 12). Two-dimensional echocardiography was employed to direct an M-mode beam through the heart to minimize measurement errors due to respiratory motion of the heart. Respiration was simultaneously recorded with M-mode echocardiograms from a minimum of five respiratory and an average of 25 cardiac cycles. Athletes had greater (p less than 0.01) end-diastolic transverse dimensions (10%), and interventricular septal and left ventricular posterior wall thicknesses (25%). During inspiration right ventricular internal end-diastolic dimensions increased (8 vs 12%) and left ventricular end-diastolic dimension (LVIDd) decreased (7 vs 8%) in athletes and controls, respectively. Although significant reciprocal changes in LVIDd (p less than 0.01) occurred during respiration, no respiratory change was noted in the transverse diameter of the heart, interventricular septal, posterior wall thickness, LV end-systolic volume or ejection fraction. Inspiration caused a 21% fall (p less than 0.01) in LV stroke volume in both groups. Eighty-four to 92% of the inspiratory decrease in LV stroke volume in the subjects studied could be attributed to ventricular interdependence; no significant interaction was found between level of conditioning and respiration. PMID- 1753735 TI - Evaluation of venous flow by light reflection rheography (LRR) in athletes performing track race. AB - The venous flow physiology in the athletes represents an interesting research field of sports angiology. The frequent observation of phlebectasias and/or varicose veins in athletes incited us to investigate the venous pathophysiological mechanisms predisposing them to such diseases. The maximal venous outflow (Rmax in millivolts) and the 1/2 venous refilling time (1/2 VRT in seconds) were evaluated in track racers, at rest and after exercise, by means of the light reflexion rheography (LRR). Thirty-two athletes (16 males, 16 females; mean age 23.4 years, range 15-37) were studied, dividing them in three groups: (A) 100 m (13), (B) 2,000 m (13), (C) 6 x 100 m with 2 minute recovery time (6). Among them six athletes performed the test wearing elastic compression stockings (25-32 mmHg). The results demonstrated a significant post-exercise modification of LRR curves and parameters in all groups, testifying superficial venous flow augmentation and deep venous flow overloading. PMID- 1753736 TI - The deterioration of visual acuity by exercise under a mesopic vision environment. AB - Visual acuity deteriorated following 15-minute bicycle ergometer pedaling under the condition of a mesopic vision environment. Visual acuity decreased sharply as the load increased. The visual functions which changed significantly after the exercise in the mesopic vision environment were visual acuity (deterioration) and accommodative near point distance (extension). PMID- 1753737 TI - Reducing induced state anxiety: effects of acute aerobic exercise and autogenic relaxation. AB - The purpose of this study was to investigate the effects of acute aerobic activity an an autogenic relaxation session on reducing induced state anxiety. Eighty-five university students were randomly assigned to one of three groups (a) aerobic, (b) relaxation, (c) control. Each group was tested separately. The general procedure consisted of anxiety induction, assessment, intervention, and assessment. The induced affect procedure involved having subjects visualize distressing images and generating high arousal states for ten minutes (Smith and Ascough, 1985). State anxiety was assessed by State-Trait Anxiety Inventory (form Y-1). The aerobic intervention lasted 40 minutes, including warm-up and cool down. The relaxation intervention consisted of listening and following instructions on a tape for approximately 30 minutes (Budzyski T, 1974, "Limb Heaviness-Exercise MU3-3"). The control group was excused after anxiety induction and told to report back in 30 minutes. The data was analyzed by a 3 x 2 (groups by time) ANOVA with repeated measures on the last factor. The groups by times interaction was significant, F(2,82) = 13.07, p less than 0.01. Post-hoc analysis using Tukey with a normalized n indicated that both the aerobic and relaxation groups significantly reduce anxiety scores from pretreatment to post-treatment but were not different from each other. Both groups were significantly different from the control. The findings support the argument that an acute aerobic activity and relaxation session can reduce induced anxiety. These results have implications for motivating individuals to engage in exercise and activity to relieve anxiety generated by an acute stressor. PMID- 1753739 TI - Exercise and migraine. A critical review. AB - Exercise has been frequently discussed as a method of migraine management, but the pathways by which exercise may alter migraines are unclear at present. The purpose of this paper is to provide a theoretical discussion of variables potentially involved in the prophylactic effects of a program of regular exercise. Exercise medicated changes to neurochemical secretory patterns, as well as symptoms commonly associated with, and thought to precipitate migraines will be discussed. Due to the paucity of experimental investigations of exercise and migraine, the bulk of supportive evidence for exercise as a treatment for migraines is gathered from related areas of research. PMID- 1753738 TI - Physical training programs and their effects on aerobic capacity and coronary risk profile in sedentary individuals. Design of a long-term exercise training program. AB - Currently the prevalent perception is that regular exercise training, besides increasing maximal oxygen uptake (VO2max), may have a beneficial effect on blood pressure and plasma lipid fractions. This is the basis for recommending exercise training for health maintenance and as a part of any prevention program for middle aged and older individuals. The purpose of this work was first, to review whether a basis exists for these recommendations and if so, to secondly design an exercise training program adjusted to these groups. Its parameters should be efficient enough to cause improvements in VO2max and risk profile, yet prevent cardial and orthopedic problems. The structure and the results of exercise programs in 27 experimental studies (n = 1153) were reviewed. The findings indicate that significant changes in VO2max, apart from individuals having least favourable values initially, do not necessarily effect simultaneous improvements in either blood pressure or plasma lipid fractions. Results strongly indicate the permanent benefits of participating in a long-term exercise program. This program should therefore provide a very useful and natural addition to the accepted dietary and pharmacological therapies. PMID- 1753740 TI - Doping test report of 10th Asian Games in Seoul. AB - With the guidance of the International Olympic Committee (IOC) the Olympic Council of Asia (OCA) introduced doping tests at the 1986 10th Asian Games at Seoul, Korea. From September 21st to October 5th, 1986, 585 samples were tested for stimulants, narcotics, anabolic steroids and beta-blockers by gas chromatography-mass spectrometry, high pressure liquid chromatography and fluorescence polarization immuno assay (TDX system by Abbott Lab.). These tests covered about 100 different drugs and another 400 as metabolites. Information about 1000 different drugs were required to interpret the drug screening data properly. The test results and outcome of findings are summarized. 3.2% of the samples were found to contain a banned drug and doping offenders were penalized accordingly. PMID- 1753741 TI - The relationship between peak torque and work of the quadriceps and hamstrings after knee injury. PMID- 1753742 TI - Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: effect of neuromuscular blocking agents on the activity of the external urethral sphincter. AB - In urethane-anesthetized rats we made a disconnection of the urinary bladder from the urethra and performed a simultaneous recording of the vesical and external urethral sphincter (EUS) pressures. Throughout the collecting phase, the EUS pressure was higher than that recorded into the bladder. Gallamine (10 mg/kg i.v.) or d-tubocurarine (100 micrograms/kg i.v.), did not alter the value of intraurethral pressure. When a reflex bladder contraction occurred in response to filling (expulsion phase) the intravesical pressure exceeded the urethral pressure and at the top of the vesical contraction a series of rapid intraluminal pressure high frequency oscillations (IPHFO) were recorded at the urethral recording site, which were abolished by neuromuscular blocking agents as well as after acute sectioning of pudendal nerves. IPHFO was still present in rats in which the periurethral muscles (pelvic floor), have been precedently dissected. To get further information about the physiological consequence of the EUS functional impairment induced by neuromuscular blocking agents, we used the non stop transvesical cystometrogram. In these conditions, blockade of the EUS did not produce passive urine dripping during the filling phase, but absence of the rhythmic striated urethral activity during the vesical expulsion phase produced a significant increase of the residual volume from 35% (control) to 75%. We present an original pharmacological method in a species whose small dimensions create technical problems for recording pressure signals from the lower urinary tract. Moreover, we have gained information on the origin of the IPHFOs and about the role of the EUS during the collecting and the expulsion phase of the voiding cycle in urethane anesthetized rats. PMID- 1753743 TI - A novel method for the evaluation of bronchoactive agents in the conscious guinea pig. AB - We describe a simple, noninvasive, nontraumatic and reproducible method in which the activities of bronchoactive agents may be recorded in six conscious guinea pigs simultaneously. The method involves the use of "head out" whole body plethysmographs from which respiratory rate can be recorded, by monitoring respiration-related changes in pressure within the body chamber. Exposure of a guinea pig to an aerosolised bronchoconstrictor agent causes an increase in respiratory rate, which is quantified by measuring the area under the respiratory rate curve using a purpose-built respiratory computer. This can be carried out for six animals simultaneously and independently. When exposed to a standard bronchoconstrictor aerosol challenge at intervals over a 6 hr period, the areas under the respiratory rate curves for each animal are highly reproducible. Inhalation of nebulized solutions of acetylcholine (ACh), histamine (Hist), 5 hydroxytryptamine, bradykinin, leukotriene D4 and the thromboxane A2-mimetic, U 46619, but not prostaglandin F2 alpha (PGF2 alpha) caused dose-related bronchoconstriction observed as increases in respiratory rate. In addition, salbutamol, clenbuterol, N-ethylcarboxamide adenosine (NECA) and PGE2 all inhibited ACh (1 mg mL-1) and Hist (1 mg mL-1)-induced increases in respiratory rate in a dose-related fashion. The method described, which is both noninvasive and nontraumatic, may therefore be used to quantify in the conscious guinea pig, both bronchoconstrictor and bronchodilator agents. PMID- 1753744 TI - A novel technique for the administration of bronchodilator drugs formulated as dry powders to the anaesthetized guinea pig. AB - A technique is described for the administration of dry powder formulations of bronchodilator drugs to the anaesthetized guinea pig. The technique has been evaluated by comparing the efficacy of several bronchodilator drugs administered either as dry powders coformulated with a lactose carrier or as nebulized solutions. In each case, the dry powder formulation had comparable bronchodilator activity and duration of action to an equivalent dose administered as a nebulized solution. This technique offers a simple and inexpensive method for the rapid screening of bronchodilator drugs without the problems associated with aerosol administration. PMID- 1753745 TI - Rabbit aortic smooth muscle cell culture. A model for the pharmacological study of diabetes-induced alterations in cell proliferation. AB - Atherosclerotic vascular disease is the most common complication of diabetes mellitus. Enhanced vascular smooth muscle cell proliferation plays a central role in atherosclerotic lesion formation. Studies using explant cultures have demonstrated that aortic smooth muscle cells from rats with experimental or genetic diabetes have enhanced rates of proliferation when compared to controls. However, this method of culture may select for cells with enhanced migratory potential. In the present studies, aortic smooth muscle cells were successfully cultured from control and diabetic rabbits after enzymatic and mechanical dispersion from thoracic aortic segments. The proliferative patterns of control cells were characterized and growth rates of diabetic cells were compared to controls. Primary cultures from control rabbits grew after an initial 5-day lag period to achieve threefold increases in cell number by 9 days. Subcultures of aortic smooth muscle cells entered the logarithmic phase of growth after 2 days, reaching the plateau phase of growth in 5-7 days and achieving three to fourfold increases in cell number. The final density to which cultures grew was not affected by the number of cells attached on day 1 for the range studied. Cells from diabetic rabbits displayed shorter doubling times and reached greater densities at confluence than did cells from controls. These data support the hypothesis that diabetes induces an atherogenic response. The dissociated rabbit aortic smooth muscle cell culture provides a model in which to study diabetes induced modulation of cell proliferation that is amenable to pharmacological manipulation to investigate agonist and growth factor-induced responses. PMID- 1753746 TI - Development of a near anesthetic-free isolated canine hindlimb model. The effects of halothane and atropine sulfate on vascular resistance. AB - A denervated, isolated canine hindlimb (HL) model was developed to minimize residual anesthetic contamination. To test the preparation, we determined the peripheral arterial vascular effects of atropine sulfate and the effect of the basal anesthetic on arterial resistance. In four dogs that were under halothane and oxygen anesthesia, the HL was prepared to allow either vascular isolation of the limb or continuity with the systemic circulation. During isolation the HL was perfused by roller pump at a preset flow rate through an infant oxygenator. Inspired gas fed to the oxygenator contained either 0%, 1.25%, or 2.5% halothane to determine that anesthetic's effect on HL arterial vascular resistance. No halothane (0%) was used in the oxygenator inflow during the atropine measurements. Vascular resistance was calculated from HL arterial pressure at constant flow. Halothane caused a significant stepwise fall in vascular resistance, with a decrease of 68% at 2.5% inspired concentration (p less than 0.01). Atropine produced a progressive attenuation of resistance that decreased by 18% after the 2.5 mg/kg dose (p less than 0.01). The model proved stable over time and demonstrated an apparent direct, dose-dependent vasodilating effect of both atropine and halothane in the canine HL muscle arterial bed. PMID- 1753747 TI - A method for rapid and frequent blood collection from the rat tail vein. AB - A technique is described for the collection of blood samples after dilation of rat tail veins using a controlled temperature device. Frequent blood samples of seven or eight per rat were collected during a 6-hr period. Further samples were taken from the same vein after recannulation during the next 5 days. This technique was also used to administer drugs intravenously through one vein and to collect blood samples from the contralateral vein. PMID- 1753748 TI - Physiological significance of metabolite channelling. PMID- 1753749 TI - Physiological significance of metabolic channelling. PMID- 1753750 TI - Metabolite channelling and metabolic regulation. PMID- 1753751 TI - Evidence of NADH channeling between dehydrogenases. PMID- 1753752 TI - Physiological significance of metabolite channelling. PMID- 1753753 TI - Are the transitory enzyme-enzyme complexes found in vitro also transitory in vivo? If so, are they physiologically important? PMID- 1753754 TI - Substrate channeling among glycolytic enzymes: fact or fiction. PMID- 1753755 TI - Energetics and control aspects of channelling. PMID- 1753756 TI - Semantics of channeling and microcompartmentation. PMID- 1753757 TI - Is channeling a disproveable hypothesis? PMID- 1753758 TI - Physiological significance of metabolite channelling: author's response to commentaries. PMID- 1753759 TI - Channeling: the pathway that cannot be beaten. PMID- 1753760 TI - Metabolite channelling in deoxyribonucleotide and DNA biosynthesis. PMID- 1753761 TI - Metabolic "channeling" and cellular physiology. PMID- 1753762 TI - Channelling in photosynthesis: the sublime and the ridiculous. PMID- 1753763 TI - How much effect on free metabolite concentrations does channelling have? PMID- 1753764 TI - Channelling by loose enzyme complexes in situ is likely, though physiological significance is open for speculation. PMID- 1753765 TI - Homeostasis, flexibility and conflict in the kinetic advantage of channelling. PMID- 1753766 TI - On the physiological significance of metabolite channelling: if, how, and where, but not why. PMID- 1753767 TI - Calmer waters in the channel? PMID- 1753768 TI - Is metabolic channelling the complicated solution to the easy problem of reducing transient times? PMID- 1753769 TI - The physiological significance of metabolite channeling: an idea whose time has come. PMID- 1753770 TI - No convincing evidence is available for metabolite channelling between enzymes forming dynamic complexes. PMID- 1753771 TI - Pillow strategy. PMID- 1753772 TI - Misleading interpretations of coupled enzyme kinetics. PMID- 1753773 TI - Channelling and evolution of metabolism. PMID- 1753774 TI - The role of isozymes in metabolite channelling. PMID- 1753775 TI - Metabolite channeling: implications for regulation of metabolism and for quantitative description of reactions in vivo. PMID- 1753776 TI - Physiological constraints on evolution of enzymes for cellular metabolic pathways. PMID- 1753777 TI - Selectivity and sensitivity improvement in co-operative systems with a threshold in the presence of noise. AB - High selectivity (specificity) and sensitivity to natural or artificial stimuli which are normally observed for biological systems can be realized in an ensemble composed of many co-operatively connected primary receptors. The co-operative interaction results in the formation of several stable states and a switching from one state to another is performed in a threshold manner. When any noise is absent the ensemble with a threshold can secure as high a selectivity and sensitivity as is desired. The presence of noise sets limits on the possible informational quality of a system because spontaneous switchings will occur. The question: What advantage as regards selectivity and sensitivity can a co operative system with a threshold have is considered quantitatively as an example for a bistable chemical system. As a result it is established that a co-operative system may have much higher selectivity and sensitivity than its individual primary receptors. PMID- 1753778 TI - Electrostatic potential and Born energy of charged molecules interacting with phospholipid membranes: calculation via 3-D numerical solution of the full Poisson equation. AB - Understanding the physicochemical basis of the interaction of molecules with lipid bilayers is fundamental to membrane biology. In this study, a new, three dimensional numerical solution of the full Poisson equation including local dielectric variation is developed using finite difference techniques in order to model electrostatic interactions of charged molecules with a non-uniform dielectric. This solution is used to describe the electric field and electrostatic potential profile of a charged molecule interacting with a phospholipid bilayer in a manner consistent with the known composition and structure of the membrane. Furthermore, the Born interaction energy is then calculated by appropriate integration of the electric field over whole space. Numerical computations indicate that the electrostatic potential profile surrounding a charge molecule and its resultant Born interaction energy are a function of molecular position within the membrane and change most significantly within the polar region of the bilayer. The maximum interaction energy is observed when the charge is placed at the center of the hydrophobic core of the membrane and is strongly dependent on the size of the charge and on the thickness of the hydrocarbon core of the bilayer. The numerical results of this continuum model are compared with various analytical approximations for the Born energy including models established for discontinuous slab dielectrics. The calculated energies agree with the well-known Born analytical expression only when the charge is located near the center of a hydrocarbon core of greater than 60 A in thickness. The Born-image model shows excellent agreement with the numerical results only when modified to include an appropriate effective thickness of the low dielectric region. In addition, a newly derived approximation which considers the local mean dielectric provides a simple and continuous solution that also agrees well with the numerical results. PMID- 1753779 TI - The energetics of embryonic growth and development. I. Oxygen consumption, biomass growth, and heat production. AB - A quantitative phenomenological model to describe the relationships between biomass growth rate, oxygen consumption, and heat production in developing embryos has been developed and tested using a wide range of experimental data. The model employs generalized material and energy balances, principles of enzyme kinetics, and an overall metabolic model scheme based on known biochemical principles. The phosphorylation concentration ratio of ATP and ADP occurs naturally and becomes a significant parameter in the analysis. The model is applied to the growth of Escherichia coli, Oryzias latipes, chick spinal cord, and whole chicken eggs. Excellent agreement between the model and the experimental data is obtained. In a succeeding paper (Part II) environmental effects and growth efficiency are discussed. PMID- 1753780 TI - Neural time-resolution depending on waveform of spikes. AB - A neural mechanism for detecting temporal coincidence in spike arrival is examined. The neurons fire when some spikes arrive simultaneously. The neurons of the electric fish can detect the coincidence in the microsecond range under hard temporal constraints: the width of spikes is more than 0.5 msec and the arrival time jitters on the scale of tens of microseconds. Since the synaptic connections between those neurons are electronic, the neural circuit is represented by a circuit composed of electric resistances. Computer simulation of behavior of the electric circuit model is presented to show that the nervous system can achieve the fine temporal sensitivity under the constraints. Analysis of the model shows that waveform of spikes is a critical condition to produce the sensitivity; peaks of spikes must be sharp. Also, the effect of the jitter of spike arrival is estimated to indicate that the coincidence detecting mechanism is tolerant of the jitter. PMID- 1753781 TI - A discrete model for immune surveillance, tumor immunity and cancer. AB - In this paper we propose a model of tumor immunity in terms of discrete automata where each automation describes the concentration of one particular type of cell involved in immune response. In contrast to the earlier models of normal immune response, there is more than one type of cell surface antigen in this model. As a consequence, the tumor can evade destruction through humoral response by changing its identity. However, the tumor can be killed by the killer cells through cell mediated response unless protected by a high concentration of the suppressor T cells. PMID- 1753782 TI - Sexual isolation in Drosophila. I. Theoretical models for multiple-choice experiments. AB - Several simple models are developed to calculate expected mating frequencies in ethological isolation experiments. They take into account the effect that the peculiar sexual behavior of Drosophila species can have in multiple-choice experiments. These models depend on only three basic parameters: male competitive ability (C), female receptivity (R) and the coefficient of females acceptance (A). Two types of model can be distinguished: (1) models with discrete preferences, in which A is a measure of the percentage of females accepting a particular kind of male and (2) models with continuous preferences, in which A represents the probability of acceptance for each courtship. It is demonstrated that the information rendered by just one experiment, although effective for determining whether sexual isolation exists, it is insufficient to estimate its degree or to demonstrate that it is asymmetrical. Further developments of the models under more complex conditions as well as their implications for reinforcement and founder effect theories are discussed. PMID- 1753783 TI - Protective effects of TJ-960 herbal mixture on hippocampal neuron damage induced by cobalt focus in the cerebral cortex of rats. AB - In the cobalt focus experimental epilepsy model, severe hippocampal neuron damage occurs with marked EEG changes. The effects of TJ-960, a herbal medicine formulation, were studied on neuron damage in the CA1 area of rat hippocampus. Continuous oral administration of TJ-960 from one month prior to the cobalt application showed almost complete protection against hippocampal neuron damage induced by cobalt application to the cerebral cortex. TJ-960 also completely inhibited the EEG changes as well as the brain edema induced by cobalt application. PMID- 1753784 TI - Antiulcerogenic effects of two Maytenus species in laboratory animals. AB - Leaves of Maytenus species are commonly used in Brazil for the treatment of gastric ulcers, dyspepsias and other gastric problems. The present study evaluated the antiulcerogenic potential of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves against ulcer lesions induced by indomethacin and cold-restraint stress in rats. Ranitidine and cimetidine were used as reference drugs. The oral and intraperitoneal administration of the extract had a potent antiulcerogenic effect against both types of ulcers. The extract was shown to cause an increase in volume and pH of gastric juice of the animals with the pH effects comparable to those of cimetidine. The results tend to confirm the popular use of the plant. PMID- 1753785 TI - Pharmacologic and toxicologic effects of two Maytenus species in laboratory animals. AB - Leaves of Maytenus species are used in the popular medicine of Brazil for their reported antacid and antiulcerogenic activity. The present work examined the effects of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves on acute administration in rats and mice, in an attempt to detect any general depressant, hypnotic, anticonvulsant and analgesic effects. General depressant and hypnotic effects were seen only after intraperitoneal administration. After chronic administration, the overall behavior of animals did not change and they continued to gain weight at the same rate as controls. Several biochemical and hematological parameters as well as pathological examination of different organs did not show any significant alterations after 3 months of treatment. A search for the potential effects of the extract on the fertility of female and male rats and on the course of pregnancy as well as a search for potential teratogenic effects did not reveal any significant differences from controls. Taken together, the results indicate that these Maytenus species may be safe for human use and deserve further investigation. PMID- 1753786 TI - Myrcene mimics the peripheral analgesic activity of lemongrass tea. AB - Oral administration of an infusion of lemongrass (Cymbopogon citratus) fresh leaves to rats produced a dose-dependent analgesia for the hyperalgesia induced by subplantar injections of either carrageenin or prostaglandin E2, but did not affect that induced by dibutyryl cyclic AMP. These results indicate a peripheral site of action which was confirmed with the essential oil obtained by steam distillation of the leaves. Silica gel column fractionation of the essential oil allowed the identification of myrcene as the major analgesic component in the oil. Identification of the components was made by thin-layer chromatography and checked by mass spectrometry. The peripheral analgesic effect of myrcene was confirmed by testing a standard commercial preparation on the hyperalgesia induced by prostaglandin in the rat paw test and upon the contortions induced by intraperitoneal injections of iloprost in mice. In contrast to the central analgesic effect of morphine, myrcene did not cause tolerance on repeated injection in rats. This analgesic activity supports the use of lemongrass tea as a "sedative" in folk medicine. Terpenes such as myrcene may constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs. PMID- 1753787 TI - Post-coital antifertility action of Ruta graveolens in female rats and hamsters. AB - Different preparations of Ruta graveolens were administered orally to female rats (Days 1-10 post coition) and female hamsters (Days 1-6 post coition). The powdered root (CDR), aerial parts (CDA) and the aerial parts aqueous extract (AEA) all showed potential anticonceptive activity in rats. Limited administration on selected days of CDA showed uniformly lesser activity than with 10-day treatment. Sequentially prepared petroleum ether and methanol extracts of CDA were as active as CDA itself. The benzene and chloroform extracts were toxic and inactive. Rutin, a known chemical constituent of the plant, was found to be inactive. None of the above preparations showed activity in hamsters. PMID- 1753788 TI - Antihepatotoxic properties of picroliv: an active fraction from rhizomes of Picrorhiza kurrooa. AB - The hepatoprotective activity of picroliv, the irridoid glycoside mixture from Picrorhiza kurrooa, was determined in adult male albino rats. Pretreatment with picroliv prevented the hepatotoxic effects of paracetamol and galactosamine as evidenced by various biochemical and histopathological observations. Maximum hepatoprotective effect was observed with daily oral doses of 6 and 12 mg/kg for 7 or 8 days. The antihepatotoxic action of picroliv seems likely due to an alteration in the biotransformation of the toxic substances resulting in decreased formation of reactive metabolites. PMID- 1753789 TI - Effects of an aqueous extract of Physalis alkekengi fruit on estrus cycle, reproduction and uterine creatine kinase BB-isozyme in rats. AB - Intraperitoneal injections of the aqueous extract of winter cherry fruits (Physalis alkekengi) to female rats produced 100% diestrus. The rats resumed their normal estrus cycle upon withdrawal of this extract. Although there was no significant decrease in the number of implantation sites, the number of pups born to rats decreased by 96% with extract administration. Treatment with this extract had no effect on body weight, uterus weight, plasma protein level or plasma total creatine kinase activity. However, the level of plasma progesterone was diminished by 44%. In addition, uterine creatine kinase BB-isozyme (an estrogen induced protein) showed a time-dependent inhibition of activity from 55% to 82%. PMID- 1753790 TI - Phytochemical screening of a Warao pharmacopoeia employed to treat gastrointestinal disorders. AB - A three-year medical-ethnobotanical investigation among the Warao of the Orinoco Delta in eastern Venezuela documented a pharmacopoeia of 100 plant species representing 45 families. Warao phytotherapists manipulate these plants in diverse manners to produce 259 remedies of various complexities to treat 52 classes of diseases/disorders. National health statistics indicate that gastrointestinal disease ranks as a principal cause of morbidity and mortality in this part of the country. Ten plant species, specifically employed by the Indians against these disorders, were subjected to phytochemical screening. Test results are listed together with the ethnoepidemiological protocol that governs the selection and administration of these medicinal plants in Warao society. PMID- 1753791 TI - Increased hepatic adenine nucleotide content by ginseng. PMID- 1753792 TI - Leukogenic effect of complex indigo powder. AB - Oral administration of complex indigo powder, an anti-scrofula powder, at a daily dose of 0.5 g/kg, raised the leukocyte count in rats injured by irradiation, but prophylactic administration could not prevent the leukopenia induced by irradiation. This dosage did not affect growth in rats and oral doses up to 6 g/kg did not induce any toxic reactions in mice. PMID- 1753793 TI - Screening of 11 ferns for cytotoxic and antitumor potential with special reference to Pityrogramma calomelanos. PMID- 1753794 TI - Ethnopharmacognostical survey of Azadirachta indica A. Juss (Meliaceae). AB - Literature data on respectively botany, chemistry, ethnopharmacology, pharmacology and toxicology of Azadirachta indica A. Juss. (Meliaceae) are reviewed and evaluated. In traditional literature, preparations of the tree are claimed to be vulnerable in wide spectrum of diseases. Especially for inflammation-related diseases a good correlation is found with the results of recent experimental investigations. In addition, a variety of other biological activities are reported. Most frequently the effects can be attributed to compounds representing the structural classes of the limonoids, phenolics and macromolecules. Reported toxicity of preparations and isolated compounds are low, except for the seed oil. In conclusion, A. indica can be regarded as a valuable plant source for the rationalisation of its use in traditional medicine and for modern drug development. PMID- 1753795 TI - Inventory of plants used in traditional medicine in Somalia. I. Plants of the families Acanthaceae-Chenopodiaceae. AB - Thirty-eight plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects. PMID- 1753796 TI - Hypoglycemic activity of Pterocarpus marsupium wood. PMID- 1753797 TI - Antibacterial, antifungal, antiamoebic, antiinflammatory and antipyretic studies on propolis bee products. PMID- 1753798 TI - Studies on the anticonvulsive, sedative and hypothermic effects of Periostracum Cicadae extracts. AB - The anticonvulsive, sedative and hypothermic effects of water and ethanol extracts of Periostracum Cicadae (PC), the cast off skin of Cryptotympana atrata were studied. The water-extract of whole Periostracum Cicadae (PCws) had anticonvulsive, sedative and hypothermic effects in rats. Orally, it decreased carrageenin-induced hyperthermia. The hypothermic effect of PCws was potentiated by 5-hydroxytryptophan and antagonized by p-chlorophenylalanine. PCws enhanced the decrease in locomotor activity induced by alpha-methyl-p-tyrosine or 5 hydroxytryptophan and reduced the increase in locomotor activity produced by levodopa plus benserazide or p-chlorophenylalanine. From these results, it was concluded that the sedative and hypothermic effect of PCws may be due to an increase in central serotonergic activity. PMID- 1753799 TI - Screening for antimicrobial activity and for alkaloids of Nauclea latifolia. PMID- 1753800 TI - On lymphedema "enigmas". PMID- 1753801 TI - Ultrastructural cytochemistry of anchoring filaments of human lymphatic capillaries and their relation to elastic fibers. AB - In previous studies "anchoring filaments" of human lymphatic capillaries have been shown to consist of microfibrils having histochemical and ultrastructural characteristics similar to elastin-associated microfibrils. When not associated with an elastin component, these microfibrils are referred to as "oxytalan microfibrils." In this study, alpha-glycol-containing carbohydrates and glycoconjugated sulfate groups, originating from sulphydryls and/or disulfide bridges, have been detected in anchoring filament microfibrils of human lymphatic capillaries by Thiery reaction (PA-TCH-SP) and "Hight Iron Diamine" cytochemical method (HID), respectively. Both of these chemical groups belong to the putative glycoprotein of which the microfibrils are constituted. Similar molecular characteristics have been demonstrated in elastic fiber microfibrils and oxytalan microfibrils of connective tissue. These findings suggest a close molecular similarity among these different types of microfibrils. Thus, whatever their individual location or denomination (anchoring filaments, oxytalan fibers, or elastin-associated microfibrils), these microfibrils form an uniform population of fibrous elements. These findings further support a structural (and functional) continuity between the lymphatic capillary wall and the elastic network of adjacent connective tissues previously described and termed "Fibrillar Elastic Apparatus" (FEA). Of interest, endothelial cells also selectively react positively to the PA-TCH-SP and HID methods. PMID- 1753802 TI - In vitro effects of a thromboxane A2-analogue U-46619 and noradrenaline on contractions of the human thoracic duct. AB - A piece of a human thoracic duct removed at operation was investigated in organ baths. The duct was cut in 8 ring segments each about 1mm long and isometric tension recorded. The segments were exposed to a potassium rich (124mM) Krebs buffer solution. In only two of the segments were contractions induced (7.2 and 1.0mN, respectively). Noradrenaline and the thromboxane mimetic U-46619 induced tonic and phasic contractions. At a noradrenaline concentration of 10(-5)M the phasic contractions had a frequency of 5 min-1. The highest frequency, 9 min-1, was recorded with 3 x 10(-10)M of U-46619 present in the bath. Noradrenaline had a mean Emax of 50% of the previous K+ (124mM)-induced contraction, and the mean pEC50-value was 6.7. The Emax and pEC50-values of U-46619 were 142% and 9.5, respectively. Postjunctional alpha-adrenoceptors and thromboxane A2-receptors may play a role in the contractility of the human thoracic duct. PMID- 1753803 TI - Lymphatics and pre-lymphatics of the rabbit pericardium and epicardium with special emphasis on particulate absorption and milky spot-like structures. AB - The lymphatics and pre-lymphatic connective tissue of rabbit pericardium and epicardium were examined by light and electron microscopy under normal conditions and after the injection of India ink and latex particles into the pericardial cavity. A characteristic lattice structure of connective tissue was present between the small mesothelial cells and the submesothelial lymphatic capillaries in the basal region of the pericardium, but not in the epicardium. Milky spot like structures bulging toward the pericardial cavity were found in the pericardium, similar to those in the omentum and mediastinal pleura. Within 60 minutes after injection, carbon and latex particles were directly absorbed through the intercellular clefts of the adjacent small mesothelial cells into the submesothelial layer particularly at sites of characteristic lattice structure. Carbon particles were already present in the lumens of lymphatic capillaries at this time. Macrophages in the pericardial cavity and submesothelial layers of the pericardium engulfed both carbon and latex particles. Our results suggest two possible routes of drainage of particulate matter from the pericardial cavity into the lymphatics: direct absorption and indirect absorption after phagocytosis by macrophages. Macrophages probably migrate from the milky spot-like structures described in this study. Epicardial lymphatics, in contrast, drain tissue fluid primarily from the myocardium. PMID- 1753804 TI - Thoracic duct cyst of the neck: a case report. AB - A thoracic duct cyst was excised from the left side of the neck of a 63-year-old woman. It was 6.5cm in length and 3.5cm in width, and was located behind the common carotid artery and jugular vein. The proximal portion of the thoracic duct with a narrowed lumen was in direct contact with the lateral surface of the cyst and the venous angle. The lower end of the cyst extended into the mediastinum to immediately above the aortic arch; the inferior portion of the thoracic duct descended from the bottom of the cyst into the mediastinum behind the aorta. The cyst was unilocular with a fluid content high in triglyceride (3350mg/dl). Its wall was muscular and permeated with lymphatic vessels. PMID- 1753805 TI - Effect of Endotelon (procyanidolic oligomers) on experimental acute lymphedema of the rat hindlimb. AB - Endotelon (Procyanidolic Oligomers, Sanofi-Labaz Laboratories) are recognized "angioprotectors" for human venous insufficiency. Using an operative experimental model of lymphedema, we sought pharmacological evidence for potential lymphagogue activity of Endotelon. After surgical interruption of hindlimb lymphatics, rats developed for 7 days, peripheral edema that represented a mean 24% increase in volume compared to the nonoperated hindlimb (control). In this experimental counterpart of acute lymphedema, Endotelon (400mg/kg/day p.o.) administered "prophylactically" (i.e., before, during, and 7 days after development of lymphedema) decreased rat hindlimb lymphedema by approximately 4.7%. When administered just before lymphedema became established (i.e., curatively), Endotelon and Coumarin (another "angioprotector") failed to affect hindlimb edema. These results suggest that Endotelon may reduce or prevent postoperative acute edema. PMID- 1753806 TI - Species variation in the extrinsic lymphatic drainage of the rodent testis: its role within the context of an immunologically privileged site. AB - Earlier work suggested that the immunologically privileged site of the rat testis was associated with anomalous testicular lymph drainage whereby some lymphatic trunks bypassed regional lymph nodes and opened directly into the systemic blood circulation via the cisterna chyli and thoracic duct. Because other workers also noted the privileged status of the testes in untreated mice and guinea pigs, we opted to examine the nature of the testicular extrinsic lymphatic system in these rodents using the rat model for comparison. Contrary to expectation, there were no direct lymphatic-venous communications draining the testes of either guinea pigs or mice. Instead, testicular lymphatics drained into at least one lymph node before reaching the blood circulation. This disparity from testicular lymphatic drainage of the rat suggests that the immunologic privilege, if any, in mice and guinea pigs has an alternative explanation (e.g., lymphatic effect of steroidal factors emanating from the testicles or adrenal gland and altering the response to foreign graft). PMID- 1753807 TI - Longitudinal Gompertzian analysis of primary malignant brain tumor mortality in the U.S., 1962-1987: rising mortality in the elderly is the natural consequence of competitive deterministic dynamics. AB - Age-adjusted mortality rates for primary malignant brain tumors (PMBT) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted PMBT mortality rate distributions between age 25 and 65 years were determined by a variable environmental factor and a common intersect point. The environmental factor declined (improved) 1.58-fold for men and 2.34 fold for women in 1987 as compared to 1962. The age at the common intersect point was 68.4 years for men and 64.1 years for women. Between 1962 and 1987, non-age standardized annual crude PMBT mortality rates increased 14.5% for men and 37.8% for women. However, PMBT mortality rates at age 77.5 years rose 259% for men and 409% for women between 1962 and 1987. Longitudinal Gompertzian analysis of PMBT mortality data suggests that rapidly rising PMBT mortality rates in the elderly are the natural consequence of competitive deterministic mortality dynamics and should not be attributed to environmental factors, past or present, that are directly contributing to PMBT mortality. Furthermore, longitudinal Gompertzian analysis demonstrates that PMBT mortality should not be studied in isolation, but rather should be examined in relation to other causes of death. When viewed from this perspective, the basis for the dramatic rise in PMBT mortality in the elderly becomes quite evident. PMID- 1753808 TI - Longitudinal Gompertzian analysis of prostate cancer mortality in the U.S., 1962 1987: a method of demonstrating relative environmental, genetic and competitive influences upon mortality. AB - Age-specific mortality rates for prostate cancer (PC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-specific PC mortality rate distributions between age 55 and 85 years were determined by a variable competitive factor and a common intersect point. The intersect point for PC occurred at age 61.5 years and mortality rate 27.9 per 100,000 and reflects genetic and environmental influences upon mortality. Between 1962 and 1987, non age-standardized annual crude PC mortality rates increased 41.6%. Longitudinal Gompertzian analysis suggests that rising PC mortality rates in the United States are the natural consequence of competitive deterministic mortality dynamics. Moreover, longitudinal Gompertzian analysis is a method that demonstrates the relative contribution of environmental, genetic and competitive influences upon disease specific mortality. PMID- 1753809 TI - Effect of lard, palm and rapeseed oils life conservation in aged mice. AB - Effects of lard, palm and rapeseed oil diets on the survival and fatty acid composition of liver and brain lipids were studied in male and female mice for 15 months. Over 80% of mice fed on lard and rapeseed oil (n-3 PUFA sufficient) diets survived to the end of feeding trial, however, 60% of male mice fed on palm oil (n-3 PUFA deficient) diet died before the end. Although a survival curve in female mice fed on palm oil diet was similar to that in male, it was not as dramatic as that of the male. The fatty acid analyses revealed that severe n-3 PUFA deficiency occurred in the mice fed on a palm oil diet. Moreover, the fatty acid was more deficient in the male than in the female. These results suggest that short life in mice may be caused by n-3 PUFA deficiency and, therefore, the fatty acid may be essential in enjoying a long life. PMID- 1753810 TI - Changes in the rat liver mitochondrial DNA upon aging. AB - During experiments on the molecular basis of morphological and functional changes observed in rat liver mitochondria upon aging, we found that the buoyant density profile of mitochondrial DNA (mtDNA) shows a wide distribution pattern especially in the lighter region than that of young rat liver mtDNA. The heterogeneous pattern may be partly recovered to become similar to that of young rat liver mtDNA by treatment with proteinase K. Therefore, it is quite likely that mtDNA of old rat liver contains firmly bound protein(s) or peptides. During the morphological observation of mtDNA by electron microscopy, we found that mtDNA of old rat had a novel property, that is, the ability to attach to negatively charged mica in the absence of magnesium ions, although their morphological features showing circular 5 microns contour length form did not change. Further, mtDNA gained resistance against EcoRI digestion during aging. This property was not shared by the DNA from young animal, and might be due to the binding protein(s). PMID- 1753811 TI - Mitochondrial theory of senescence: respiratory chain protein studies in human skeletal muscle. AB - In view of a previously demonstrated negative correlation between stage III respiratory activity in human mitochondria and increasing age, the relationship between human respiratory chain complex protein content and age was investigated. Quantitative immunoblot studies were carried out using holo complex I, III and IV antibody probes in human skeletal muscle mitochondrial homogenate from patients of varying ages. No significant negative correlation between increased age and respiratory complex chain protein content was seen for either total complex activity or for any of the subunits which could be reliably identified. As respiratory complex protein content is preserved with ageing, the decrease in respiratory efficiency is likely to follow aggregation of mutations in structural mitochondrial (mt) DNA genes which do not interfere with mt DNA transcription and protein translation rather than mutations in mt tRNA or ribosomal RNA genes. This is consistent with the fact that mt genes involved in protein translation only occupy a fairly small percentage of the mitochondrial genome. PMID- 1753812 TI - [The evidence of human immunodeficiency virus infection in the seronegative subjects of high-risk groups]. AB - BACKGROUND: Polymerase chain reaction (PCR) is a new diagnostic procedure which has been used to recognise HIV-infected individuals who remain seronegatives. METHODS: Genomic DNA isolated from the peripheral blood mononuclear cells of 90 high-risk individuals were analyzed by PCR using gag primers SK 38/39. Subjects were classified in four groups: 42 drug abusers, 35 heterosexual partners of HIV infected individuals, 9 homosexual men, and 4 health care workers accidentally exposed to HIV. Liquid hybridization using radiolabelled probes was done to confirm the results. All samples were also tested for HIV antigen and antibodies (Ab) using EIA and Western blot (WB). RESULTS: Two out of 11 (18%) drug abusers and 5 out of 34 (14%) couples were PCR positive in absence of HIV antibodies. This silent HIV infections were not recognized in homosexuals and health care workers. All 38 seropositive samples were PCR positive. None of the samples PCR+/Ab- was positive for HIV antigenemia or showed indeterminate results in the WB assay. CONCLUSIONS: Silent HIV infections were recognized in drug abusers (18%) and couples of HIV-infected individuals (14%). Mechanisms involved in the production of this "occult" HIV infections are reviewed. PMID- 1753813 TI - [The use of the determination of plasma theophylline concentrations in the hospital]. AB - BACKGROUND: The evaluation of the determination of plasmatic concentrations of theophylline (PCT) in clinical practice is scarce. An observational study was carried out with the aim of discerning the reasons why PCT determinations are requested, the theophyllinemias obtained and the attitude of the medical staff in a hospital. METHODS: PCT determinations obtained in 113 patients over a period of 3 months were analyzed. Information concerning treatment and daily doses of theophylline, reasons for theophylline determination, apart from those included in the request for theophyllinemia determination, clinical history and treatment sheets were collected. RESULTS: Treatment with theophylline had been indicated in 78 patients (69%) with chronic bronchitis, and 30 (26%) with asthma. All the patients received medication in addition to theophylline. Daily dosage (SD) was 734 (260) mg and the daily doses as to body weight (SD) was 11 (4) mg/kg/day. 188 DNPT were performed, however 22 (12%) were inadequate; of the remaining 166 PCT determinations 117 (69%) had been requested with no indication of insufficient clinical response, suspicion of undesirable effects or modifying factors of the pharmacokinetics of theophylline. The mean plasmatic concentration (SD) was 11.3 (7) micrograms/ml. PCT was infratherapeutic in 74 PCT determinations (44%), therapeutic in 73 (44%) and toxic in 19 (11%). Therapeutic concentrations were obtained in only 16 (35%) of the 45 patients in whom a second PCT determination had been carried out. CONCLUSIONS: In this study scarce individualization in the indication of treatment and the doses of theophylline administered are observed. The reason for soliciting determination of theophyllinemia and dosage adjustment in terms of plasmatic concentrations are also commented upon. PMID- 1753814 TI - [The mycoplasmas isolated from respiratory specimens]. AB - BACKGROUND: Mycoplasma pneumoniae is the species that is considered pathogen for respiratory tract. Other species, M. hominis and U. urealyticum, have been isolated from respiratory specimens and its aetiological relation with respiratory infections is not clear. METHODS: In this study, mycoplasma from respiratory specimens have been isolated from HIV infected patients, patients suffering from chronic bronchitis and patients with respiratory infections without any underlying disease, using SP-4 media and being identified with glucose fermentation test, guinea pig blood cells adsorption, tetrazolium reduction, urea test, arginine test, and antigenic study by an immunoassay on the colonies grown on SP-4 solid medium. RESULTS: M. hominis has been the species most frequent isolated, mainly from patients without any underlying disease and from HIV infected patients, and less frequently from patients suffering from chronic bronchitis, the differences between both groups being significative. Other Mycoplasma, no identified at he species level, have been isolated although without any significative differences. In only one case U. urealyticum has been isolated. CONCLUSIONS: No M. pneumoniae isolation was obtained. PMID- 1753815 TI - [The measurement of health status in cardiology]. PMID- 1753816 TI - [Lipomatous hypertrophy of the interauricular septum as a cause of cerebral embolism in a patient with isolated Wernicke's aphasia]. AB - The clinical observation of a 74 year old male presenting isolated Wernicke's aphasia due to a temporal left infarction of cardiac embolic origin secondary to paroxysmal auricular flutter is described. Transthoracic and transesophageal echocardiography, computerized tomography and magnetic resonance provided characteristic images which permitted the establishment of the diagnosis of lipomatous hypertrophy of the interauricular septum without requiring the use of invasive techniques. Lipomatous hypertrophy of the interauricular septum is a cardiac tumor of unusual presentation constituted of an abnormal accumulation of non-encapsulated fatty tissue which occupies a thickness greater than 15 mm of the interauricular septum. Wernicke's aphasia as a form of presentation of the lipomatous hypertrophy of the interauricular septum has not previously been described in the literature. PMID- 1753817 TI - [The current situation of tuberculosis in Spain]. PMID- 1753818 TI - [Benign intracranial hypertension following the suspension of corticotherapy in a female patient previously operated on for Cushing's disease]. PMID- 1753819 TI - [Acute pancreatitis induced by erythromycin: a new case]. PMID- 1753820 TI - [The investigation of food poisonings: the first step for their control]. PMID- 1753821 TI - [Mediastinal involvement due to an inflammatory pseudotumor of the lung]. PMID- 1753822 TI - [Paraproteinemias in patients infected with the human immunodeficiency virus]. PMID- 1753823 TI - [The current indications for lumbar puncture in cerebrovascular disease]. PMID- 1753824 TI - [Visceral leishmaniasis with partial response to ketoconazole in a patient with positive antibodies to the human immunodeficiency virus]. PMID- 1753825 TI - [The effect of inhaled pentamidine in the radiology of Pneumocystis carinii pneumonia]. PMID- 1753826 TI - [A multicenter study of the breaking of the smoking habit with nicotine chewing gum in health personnel]. AB - BACKGROUND: The health professionals have a leading role in the reduction of the smoking prevalence. Spain has one of the big rate of "per capita" tobacco consumption in the world, and the Spanish doctors have the biggest prevalence of smokers among their colleagues from the EEC countries. METHODS: The effectiveness of a stop smoking programme in health care professionals was evaluated. This programme combined group therapy, nicotine chewing gum and behavioural assistance through the evaluation of CO contained in expired breath; and it is being applied with good results between the smokers of general population in Spain. A total of 211 voluntary smokers working in Spanish six general hospitals were treated, from those 149 (71%) were physicians and nurses (PS) and 62 (29%) others professionals without sanitary responsibilities (PNA). RESULTS: At one year follow-up, 64 (30%) were not smoking, and the P.S. had a higher rate of give up than the PNA (p less than 0.05). Specifically the women of P.S. obtained a greater issue than the women of PNA (p less than 0.05). Both, nicotine chewing gum and behavioural assistance were as effective as usual in smoking cessation programme like this, in our country. CONCLUSIONS: Although the outcome is lower than the obtained with the same approaches in smokers from general population, the better results of the PS than the PNA imply a good change of attitude of them. Specially the women PS obtained a big success, and this is outstanding in this group with a great prevalence of smokers, increasing in the recent years. The subjects who give up smoking increased their corporal weight less than the observed in smokers of the general population, who also give up with this treatment. PMID- 1753827 TI - [An analysis of the effect of tobacco on glucose metabolism]. AB - BACKGROUND: The nicotine contained in tobacco smoke produces an elevation of the plasmatic catecholamines which, in turn, may be the cause of the increase in basal glycemia by several mechanisms. The aim of this study was to investigate the relation between cigarette consumption and the increase in glucose in smokers and non smokers. METHODS: Basal glycemia and glucosylate hemoglobin (HbA1c) were determined in 74 males, 38 smokers and 36 non smokers who were consulted and included in the prevention activities program of the center. RESULTS: Significantly greater fasting glycemia was found in smokers than in nonsmokers. However, upon analyzing the values of glucosylate hemoglobin no significant differences were observed between the two groups. CONCLUSIONS: These data suggest that nicotine contained in tobacco smoke produces a transitory hyperglycemia. PMID- 1753828 TI - [The real efficacy of breaking the smoking habit]. PMID- 1753829 TI - [Hybridization in situ: its diagnostic applications in the field of leukemia and lymphomas]. PMID- 1753830 TI - [Waldenstrom's macroglobulinemia, cryoglobulinemia type I and membranous glomerulonephritis]. AB - Renal complications in Waldenstrom's macroglobulinemia (WM) are infrequent and are characterized by the presence of PAS positive amorphous hyaline deposits in the capillary lumen, infiltrated with lymphoplasmatic cells with PAS positive inclusions in the interstices and intratubular hyaline cylinders. Membranous glomerulonephritis may be a paraneoplastic manifestation of the lymphoproliferative processes. A 67-year-old male was diagnosed of WM, type-I cryoglobulinemia with renal insufficiency without proteinuria. Renal histological examination revealed changes characteristic of nephropathy associated to WM as well as membranous glomerulonephritis. This association has not been described previously. The coexistence of two pathogenic mechanisms with a common base, lymphoproliferative disease, may explain this association. PMID- 1753831 TI - [Notes from the Antilles. Vive la difference?]. PMID- 1753832 TI - [The efficacy of hemoperfusion in acute poisoning by tricyclic antidepressants]. PMID- 1753833 TI - [Persistent hiccups as the sole manifestation of reflux esophagitis]. PMID- 1753834 TI - [A primary brain abscess due to Actinomyces in a patient with congenital cyanotic cardiopathy]. PMID- 1753835 TI - [The attitude toward the terminal patient in primary care teams]. PMID- 1753836 TI - [Escherichia coli bacteremia resistant to ciprofloxacin]. PMID- 1753837 TI - [Rapidly progressive kidney failure and amyloidosis AA]. PMID- 1753838 TI - [Autoimmune hemolytic anemia as a symptom of the onset of a MALT lymphoma]. PMID- 1753839 TI - [Synchronous pulmonary and renal neoplasms]. PMID- 1753840 TI - The London School of Hygiene and Tropical Medicine: a child of many parents. PMID- 1753841 TI - Alfred Swaine Taylor, MD, (1806-1880): forensic toxicologist. PMID- 1753842 TI - Surgery in ancient Mesopotamia. PMID- 1753843 TI - "Matrix and the pain thereof": a sixteenth-century gynaecological essay. PMID- 1753844 TI - Application of the argon laser to dentistry. AB - A review was conducted to determine specific areas of application of the argon laser to dentistry. When appropriate, comparisons between the argon laser and other treatment methods were made. It was concluded that the argon laser has applicability in composite resin placement, in enamel and dentin bonding procedures, in preventive dental therapies, and in endodontic procedures. PMID- 1753845 TI - Selectivity, efficiency, and surface characteristics of hard dental tissues ablated with ArF pulsed excimer lasers. AB - Lasers are finding expanding applications in the field of dentistry. Cutting in soft tissue, hard dental material ablation, caries removal, and root canal therapy are only a few examples of dental laser uses. In this article, the application of short pulse ArF excimer laser to ablation of dentin and enamel is investigated. In particular, the effect of laser pulse repetition rates (PRR) and fluence levels on the efficiency of the ablation process and on the average thermal response of ablated surfaces is investigated. Ablation of dentin was found to be considerably more efficient than the ablation of enamel and depends exponentially on the laser fluence. Both dentin and enamel surfaces showed an increase in surface temperature with repetition rate. At lower PRR, however, temperature increases are very small. Surface temperature was also found to increase with laser fluence, although this increase is very small at laser PRR of 5 Hz or less. Tissue ablation rates were found to be comparable to or better than other nanosecond lasers, and left smooth surfaces, free of thermal damage. Microscopic examination of the ablated surface shows no crack formation, charring, discoloration, or any other thermal damage. The ablated surfaces appear to be very smooth, highly polished, and glossy looking as if they were subjected to thermal melting. This observation is indeed confirmed under scanning electron microscopy (SEM), where evidence of localized melting of the tissue is observed. Furthermore, a close SEM examination of the dentin surface reveals a selectively ablated intertubular dentin, while the remaining pillar-like dentin tubules are sealed off with fused peritubular dentin. At all fluence levels and PRR, the first three to four pulses impinging on an untreated enamel surface produced unusually large plumes of debris which were different in size, texture, and fluorescence emission characteristics from the ablation products of subsequent pulses. It is believed that these different ablation characteristics are a consequence of the pulsed ArF laser's ability to selectively remove residual matter from the more resistant enamel surface. PMID- 1753846 TI - Laser-assisted microvascular anastomosis using CO2 and KTP/532 lasers. AB - The milliwatt carbon dioxide (CO2) laser has been shown to be an effective device for performing laser-assisted microvascular anastomosis (LAMA) with consistently high patency rates, minimal tissue disruption, and rapid surgical time as well as the potential for reduced inflammation due to fewer foreign bodies (sutures) in the wound. The purpose of this investigation was to determine the feasibility of using the potassium titanyl phosphate (KTP) laser to perform LAMA and to compare it to CO2 LAMA in both arteries and veins. Patency rates, inflammatory response, and course of healing were evaluated through histological analysis. Twenty-eight rats were divided into two groups, which underwent either CO2 or KTP LAMA and then were sacrificed at 3 days, and 1, 2, 4, 8, and 12 weeks postoperatively. Patency rates for arteries and veins were comparable for both wavelengths (CO2: 100% for arteries, 93% for veins; KTP: 93% for arteries, 93% for veins). Histological grading of inflammation and fibrosis showed no significant difference between the two groups. This study demonstrated the efficacy of using the KTP/532 laser in performing LAMA. We found the KTP and CO2 LAMA to have comparable patterns of tissue damage and course of healing. Although this experiment did not investigate the mechanism(s) of tissue welding, our results suggest that successful LAMA may be independent of wavelength. PMID- 1753847 TI - Contact Nd:YAG tonsillectomy: effects on weight loss and recovery. AB - Contact Nd:YAG tonsillectomy using synthetic sapphire blades appears to meet or exceed standards established by spot monopolar cautery. Subjects' percentage of weight loss and return to work/social activities was measured and the laser group displayed less percentage of weight loss, faster return to pre-operative weight, and less recovery time than the comparative cautery group. Because of the unique nature of Nd:YAG laser light combined with sapphire blades, special consideration should be given to these accessories by physicians before attempting tissue cutting and vessel coagulation. The author believes that the extent of physician training and proficiency may be key to the success of soft tissue head and neck applications, such as tonsillectomy, which will have an effect on the outcome of clinical data. PMID- 1753848 TI - Laser-induced fluorescence emission: I. The spectroscopic identification of fibrotic endocardium and myocardium. AB - Laser-induced fluorescence has been developed as a guidance system for laser angioplasty. Laser ablation has been used for resection of arrhythmogenic ventricular scar. We have investigated the use of laser-induced fluorescence for the detection of fibrotic and ischemic changes in endocardium and myocardium. Fluorescence emission spectra from human necropsy specimens were correlated with histologic examination. Normalized fluorescence intensity detected from both the endocardial and the myocardial surfaces of the fibrotic ventricular specimens was significantly higher than that of corresponding normal specimens at 440 to 475 nm. Fibrotic endocardium could be identified by a fluorescence emission intensity ratio less than 1.5 for wavelength ratio 375/450nm. Acutely infarcted endocardium was recognizable by a ratio of 1.5 to 2.0. The specificity and sensitivity of detection of scarred endocardium was 70 and 100%, respectively. Fibrotic myocardium was also consistently identified by fluorescence spectroscopy. CONCLUSION: Fluorescence emission spectroscopy can differentiate normal and fibrotic endocardium and myocardium, in vitro. This technique may be useful for guidance during laser ablation of arrhythmogenic ventricular scar. PMID- 1753849 TI - Alternative lasers for endoscopic surgery: comparison of pulsed thulium-holmium chromium:YAG with continuous-wave neodymium:YAG laser for ablation of colonic mucosa. AB - Precise and controllable tissue vaporization is essential for minimizing risk in removal of sessile polyps from the lumen of thin walled gastrointestinal organs such as the colon. We compared the ablative efficiency on canine colonic mucosa of the THC:YAG laser with the clinically employed cw Nd:YAG laser. Fresh canine colon was treated with a progressive dose schedule using each laser at several energy/power densities. Ablation depth was measured on fresh tissue and thermal (non-ablation or coagulative) damage examined histologically. The THC:YAG ablation rates were 13.7 +/- 0.8 and 10.2 +/- 0.4 microns/J at 55 and 85 J/cm2, respectively. The Nd:YAG laser generated 3.7 +/- 0.3, 2.8 +/- 0.1, and 3.6 +/- 0.2 microns/J at 4,460, 5,095, and 5,730 W/cm2, respectively. There was a significant (P less than 0.001) difference among the THC:YAG ablation rates and between the THC:YAG and Nd:YAG ablation rates (ANOVA). The THC:YAG laser craters had significantly less collateral thermal damage than Nd:YAG. The pulsed THC:YAG laser should have an important clinical role since its use could reduce the risk of perforation in endoscopic laser procedures such as the removal of sessile polyps. PMID- 1753850 TI - Solid state ultraviolet laser (213 nm) ablation of the cornea and synthetic collagen lenticules. AB - We used a Q-switched Nd:YAG laser with non-linear optical crystals to produce the 5th (213 nm) and the 4th (266 nm) harmonic frequencies. Using these two wavelengths, we ablated fresh porcine corneas and type I collagen synthetic epikeratoplasty lenticules. For the 213-nm ablation, radiant exposure was 1.3 J/cm2. The ablation rate was 0.23 micron per pulse for the epikeratoplasty lenticules. We examined all tissues with light microscopy, transmission electron microscopy, and scanning electron microscopy. Histology for the 213-nm ablation showed a clean ablation crater with minimal collagen lamellae disruption and a damage zone less than 1 micron. In comparison, the 266 nm radiation showed more charring at the edges with a damage zone approximately 25 microns deep with disruption of the stromal lamella. Our results show that this solid state UV laser is a potential alternative to the excimer laser for cornea surgery. PMID- 1753851 TI - Technique for cellular microsurgery using the 193-nm excimer laser. AB - A new cell surgery technique has been developed to produce well-defined alterations in cells and tissue without detectable heating and/or other structural damage in the surroundings. The technique involves the use of an argon fluoride excimer laser, in the deep ultraviolet (UV) region of the spectrum at 193 nm, which is guided through a glass pipette filled with a positive air pressure. To demonstrate the method, holes were drilled in the zona pellucida of mouse oocytes. The diameter of the drilled hole was determined by the pipette tip size, and its depth by an energy emitted per pulse and number of pulses. Scanning electron microscopy of the drilled mouse oocytes showed uniform, round, well circumscribed holes with sharp edges. Oocytes that had their zona pellucida drilled with this new method fertilized in vitro and developed to the blastocyst stage in a rate similar to that of control group. These results demonstrate the nonperturbing nature of this cold laser microsurgical procedure. In addition to the extension of our results for clinical in vitro fertilization purposes, such as enhancement of fertilization and embryo biopsy, there are wide-ranging possible uses of our method in fundamental and applied investigations that require submicron accuracy in cellular alteration. PMID- 1753852 TI - Temperature response of biological materials to pulsed non-ablative CO2 laser irradiation. AB - This paper presents surface temperature responses of various tissue phantoms and in vitro and in vivo biological materials in air to non-ablative pulsed CO2 laser irradiation, measured with a thermocamera. We studied cooling off behavior of the materials after a laser pulse, to come to an understanding of heat accumulation and related thermal damage during (super) pulsed CO2 laser irradiation. The experiments show a very slow decay of temperatures in the longer time regime. This behavior is well predicted by a simple model for one-dimensional heat flow that considers the CO2 laser radiation as producing a heat flux on the material surface. The critical pulse repetition frequency for which temperature accumulation is sufficiently low is estimated at about 5 Hz. Although we have not investigated the ablative situation, our results suggest that very low pulse frequencies in microsurgical procedures may be recommended. PMID- 1753853 TI - Contact Nd:YAG laser potentiates the tumor cell killing effect of hyperthermia. AB - This study was carried out to investigate the effects of Nd:YAG laser-induced hyperthermia on murine F9 embryonal carcinoma cells in vitro using various power settings, temperatures, and exposure times. F9 cells were plated on gelatin coated dishes, treated on the following day, and cultured overnight. The following day the killing efficiency of the treatments was estimated by staining the dishes or by labeling the cells with 3H-thymidine. A contact Nd:YAG laser with a frosted-end probe was used. After laser treatments at 39 degrees C, no significant changes were observed in the viability of the cells. Laser treatment at 43 degrees C killed F9 cells, and the effect was related to the power setting used. Using 6 W, the quantity of viable cells progressively decreased after 1-, 2 , and 5-min treatments, and no viable cells were found after a 10-min treatment. Using 10 W, approximately 10% of the cells survived a 1-min laser treatment, but all cells were killed after a 2-min treatment. In the control wells, heated in a water bath for up to 40 min, all cells regularly survived at 43 degrees C. There were much less viable cells in those laser-treated wells where the temperature exceeded 44 degrees C than in those where the temperature was kept at 44 degrees C. In conclusion, the tumoricidic effect of hyperthermia can be potentiated by the use of the contact Nd:YAG laser. At a set temperature the cell killing effect of laser treatment is dependent on the power used and the duration of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753854 TI - Laser beam diameter for port wine stain treatment. AB - Optimal port wine stain treatment requires the selective absorption of light by the ectatic blood vessels. We investigated whether deeper blood vessels can be coagulated, without damaging other cutaneous structures, by varying the laser beam diameter. The penetration of the light was simulated with a random walk (Monte Carlo) program. Scattering of the light plays a major role: practically all light that is absorbed in a blood vessel in the dermis is scattered light. In the epidermis, where the distribution is more centered, a larger beam diameter does not increase the energy density as much as deeper within the dermis where the blood vessels lie and where the light is totally diffuse. Increasing the laser beam diameter from 200 microns to 1 mm or more, makes a typical blood vessel absorb 2.5 times more energy, while the energy absorbed by the epidermis remains the same. The larger the laser beam diameter the better the treatment. PMID- 1753855 TI - Histochemical evaluation of the coagulation depth after argon laser impact on a port-wine stain. AB - A two-step excisional treatment of a port-wine stain (PWS) on the back of a 43-yr old female patient was performed. Immediately before the first surgical treatment, two corresponding series of argon laser impacts were performed, each on one PWS half. Different laser parameters with irradiances ranging from 95 to 382 W/cm2 and energy fluences ranging from 19 to 114,6 J/cm2 were used. Laser spots on the first part ot be excised were biopsied 10 min after laser treatment and prepared for histochemical analysis by staining with nitro blue tetrazolium chloride (NBTC). Reduction of this redox dye by nicotinamide adenine dinucleotide diaphorase (NADH-diaphorase) leads on frozen tissue sections to an intense blue precipitate. The activity of NADH-diaphorase subsides immediately upon cell damage. All vital epidermal and dermal cells presented a dense blue granular pigment in their cytoplasm, sparing the nuclei. Laser induced arc-shaped epidermal and dermal necrosis did not stain, showing a clear demarcation from surrounding vital tissue. The depth of the thermal injury ranged from 0.28 to 0.45 mm; it did not correlate with the chosen fluences. With these penetration depths, the vast majority of PWS vessels was affected. Assessment of the remaining part of the PWS 8 months later yielded blanching of all laser-treated areas. With the NBTC method, an accurate definition of laser-induced tissue damage is feasible. It could be shown that the exposure time is the most relevant parameter influencing the penetration depth. PMID- 1753856 TI - 585 nm for the laser treatment of port wine stains: a possible mechanism. PMID- 1753857 TI - [Current status and main trends in the development of the equipment for inhalation anesthesia]. PMID- 1753858 TI - [Trends in the development of the equipment for artificial ventilation of the lungs]. PMID- 1753859 TI - [Development of the electrotherapeutic, physiotherapeutic and surgical equipment (materials of the international exhibition "Public health-90")]. PMID- 1753860 TI - [Ultrasonic scanning diagnostic equipment (materials of the exhibitions "Public health-90" and "Maternal and child health care-90")]. PMID- 1753861 TI - [Endoscopic techniques: their status and developmental trends]. PMID- 1753862 TI - [Development of the equipment for radionuclide diagnosis]. PMID- 1753863 TI - [Trends in the development of technical equipment for psychophysiological studies]. PMID- 1753864 TI - [Stomatological materials presented at the international exhibition "Public health-90"]. PMID- 1753865 TI - [Continuous sterilization of peritoneal dialysate using ultraviolet rays]. AB - A unit for continuous ultra-violet sterilization on the basis of a mercury-UV low pressure lamp was devised and tested. It differs from the known analogs in the capacity of separating into layers of the monolithic flow of a solution and of using the entire arsenal of direct rays emitted by the source. The output is 400 ml/min. The irradiation dose exceeds 163 times the optimal one for spores. The authors provide a mathematic depiction of the unit operation. A linear relationship was established between the growth of optical density of the solution and the irradiation dose. About 100 tons of the peritoneal and replacement (for hemofiltration) solutions were sterilized and utilized. PMID- 1753866 TI - [Radionuclide radiation monitoring]. AB - Radionuclide radiation monitors used nowadays can operate fairly well in measuring the parameters of the radiation type for which they are intended and calibrated. However, in many cases (particularly in emergency situations) the detector is exposed at a time to several types of radiation. Under such conditions its readings may be noticeably influenced by concomitant radiation. In view of this fact interpretation of the measurement data is embarrassing. Bearing this in mind, it is advisable that the available monitors be modernized and new ones be devised for mixed radiation with the common equivalent surface thickness amounting to 1 g/cm2 of tissue equivalent substance. PMID- 1753867 TI - [A device for the treatment of dislocations and subluxations of the temporomandibular joint]. AB - An extraoral approach to the treatment of dislocations and subluxations of the lower jaw by means of a special outfit holds promise since it has no contraindications, does not cause any complications, fully preserves lower jaw function, shortens the treatment period, and enables surgical interventions to be avoided. The outfit is attached to the patient's head and is only removed overnight. The treatment may last 1.5 to 3 months. PMID- 1753868 TI - [A device for fixation of partial removable dentures in cases of single-standing teeth]. AB - An outfit for fixing removable dentures in single standing teeth contains internal and external telescopic crowns. The latter is fitted out with a clasp and a cut-out on the oral surface. In order to enhance the design rigidity and denture fixation safety, the two-layer internal crown is placed on the vestibular and approximate surfaces, whereas the clasp on the external layer thereof. PMID- 1753869 TI - [Use of a laser optometer for the control of visual fatigue in workers in the precision instrument industry]. PMID- 1753870 TI - [A pulsimeter]. PMID- 1753871 TI - [A new equipment of the "Polius" series for electromagnetic therapy]. PMID- 1753872 TI - [Diathermic biopsy forceps for flexible endoscopes]. PMID- 1753873 TI - [Instruments for measuring arterial blood pressure at the international exhibition "Public health-90"]. PMID- 1753874 TI - [Measuring equipment for instrumental diagnosis of eye diseases]. PMID- 1753875 TI - Lysophospholipase activity of Ascaris suum-induced mouse peritoneal neutrophils and eosinophils. AB - Lysophospholipase activity of mouse peritoneal neutrophils and eosinophils was studied to determine if neutrophils and eosinophils have lysophospholipase activity when treated with Ascaris suum whole worm extract, if zymosan activated complement can induce increased lysophospholipase activity, or if the immune status of the host has an effect on lysophospholipase activity. Neutrophils from noninfected or infected (immunized) mice were found to have increased lysophospholipase activity when treated with A. suum whole worm extract or zymosan activated complement demonstrating neutrophils as a source of lysophospholipase activity in the presence or absence of an immune response. Eosinophils from immunized mice had increased lysophospholipase activity when treated with either A. suum whole worm extract or zymosan activated complement. PMID- 1753876 TI - Effects of vaccinia virus-expressed interleukin 2 on the immune system of sublethally irradiated mice. AB - Vaccinia virus that expressed interleukin 2 (IL 2) was cleared from immunodeficient irradiated mice more efficiently than virus that did not express interleukin 2. These results extend the previously observed protection from nude mice to another model of immunodeficiency. No antibody or cytotoxic T lymphocyte response could be detected in sublethally irradiated mice that had been inoculated with IL 2-expressing vaccinia virus, but levels of splenic natural killer cell activity were elevated. Sublethally irradiated mice that had recovered from IL 2-plus hemagglutinin-expressing vaccinia virus were partially protected against both influenza virus and vaccinia virus. These results indicate that vaccinia virus-expressed IL 2 mediates clearance of primary viral infection via a mechanism that does not involve antibody or cytotoxic T lymphocytes. They also indicate that inclusion of lymphokine genes in live recombinant viral vaccine vectors may increase vaccine safety. PMID- 1753878 TI - rIL-1 alpha enhances adoptive transfer of resistance to Listeria monocytogenes infection. AB - We have previously demonstrated that administration of recombinant rIL-1 alpha enhances resistance against Listeria monocytogenes infection in mice. In this study we considered the possibility that this cytokine might also augment adoptive immunity conferred by the transfer of listeria-immune spleen cells. Concomitant administration of rIL-1 alpha with large numbers (2 x 10(7) or 10(8)) of listeria-immune spleen cells reduced the protection mediated by the transferred cells. Conversely, rIL-1 alpha co-administered with suboptimal numbers (1-5 x 10(6)) of immune splenocytes augmented anti-listeria resistance in an additive fashion. Although transfer of 10(6) listeria-immune spleen cells alone did not result in significant protection, when 10(6) immune cells were incubated with rIL-1 alpha prior to transfer they conferred significant protection to naive recipients. Time course experiments indicated that the greatest protection was achieved when listeria-immune spleen cells were pretreated with rIL-1 alpha for 2 h prior to adoptive transfer. The protection transferred by 10(6) rIL-1 alpha-pretreated immune spleen cells was not inhibited by TGF beta. This study is the first to use rIL-1 alpha to potentiate the adoptive transfer of resistance to an infectious agent by immune cells. PMID- 1753877 TI - Effect of human chorionic gonadotropin (hCG) on Neisseria gonorrhoeae invasion of and IgA secretion by human fallopian tube mucosa. AB - The possible effect of human chorionic gonadotropin (hCG) on the mucosal immune response and susceptibility of the fallopian tube mucosa to invasion by Neisseria gonorrhoeae (gonococci) was investigated in the fallopian tube organ culture (FTOC) model. Immunohistochemical and radioreceptor assay techniques showed specific high affinity binding of hCG in vitro to the apices of non-ciliated fallopian tube cells (Kd approximately 10(-9) M). Continuous exposure of the FTOC mucosa to hCG during infection with gonococci resulted in a marked increase (6- to 15-fold) in IgA secretion and significantly reduced gonococcal invasion (invasion score range 0.7 to 1.75) compared to infected control tissue which was not exposed to hCG (invasion score range 2.9 to 4.95, P less than or equal to 0.01). By contrast, exposure of the mucosa to hCG during the 24 h preceding gonococcal infection followed by the removal of hCG from the system at the time of infection resulted in enhanced gonococcal invasion (invasion score range 7.95 to 9.7, P less than 0.001). We conclude that hCG can modulate the mucosal immune response and susceptibility of fallopian tube epithelium to gonococcal invasion. PMID- 1753879 TI - Neutralizing monoclonal antibodies to Pasteurella haemolytica leukotoxin affinity purify the toxin from crude culture supernatants. AB - The leukotoxin of Pasteurella haemolytica is a major virulence factor of the organism. It is an unstable protein which has proven very difficult to purify using traditional techniques. Hybridomas secreting monoclonal antibodies (mAbs) to P. haemolytica leukotoxin were derived from spleen cells of a mouse immunized with crude culture supernatant. Five hybridomas secreting mAbs specific for the leukotoxin were stabilized. Each of the mAbs reacted with a protein of approximately 100 kDa in toxic culture supernatants, and two of them completely neutralized the toxin in vitro. Affinity chromatography of crude culture supernatant on a column prepared with one of the neutralizing mAbs resulted in the isolation of biologically active toxin. PMID- 1753880 TI - Interleukin 5 (IL-5) and its receptor. PMID- 1753881 TI - Separation of the prodigiosin-localizing crude vesicles which retain the activity of protease and nuclease in Serratia marcescens. AB - Crude vesicles in which prodigiosin is localized were separated from pigmented Serratia marcescens. The bacteria were grown on peptone-glycerol agar plate, suspended in saline, and fractionated into cells, vesicles, and supernatant by differential centrifugation. Electron microscopic observations showed that the fractionation was conducted properly and the separated vesicles were lysed in distilled water. The vesicles suspended in saline retained 100 kilodalton protein of which amount is correlated with prodigiosin level, but the 100 kDa protein was found in the supernatant when the vesicles were lysed in distilled water. The vesicle fraction retained few colony-forming units and little detectable activity of NADH oxidase, but showed much higher activities of protease and nuclease than the cell fraction. The profiles of the activities of the protease and the nuclease in the fractions were different from each other, that is, the protease activity in the vesicle fraction was lower than that in the supernatant fraction, whereas the nuclease activity in the vesicle fraction was higher than that in the supernatant fraction, suggesting that the two extracellular enzymes were released from the pigmented bacteria by different mechanisms. PMID- 1753882 TI - Examination of host defense factors responsible for experimental chronic respiratory tract infection caused by Klebsiella pneumoniae in mice. AB - We have studied the host defense factors that operate during the course of chronic respiratory tract infection caused by Klebsiella pneumoniae 27 in CBA/J mice. A large number of polymorphonuclear leukocytes (PMNs) rapidly infiltrated the alveolar spaces after infection. Treatment with cyclophosphamide (CY) before infection greatly reduced the infiltration of PMNs and caused an increase in bacterial counts. CY treatment of mice in the chronic phase also caused bacterial proliferation in the lungs. The administration of a high titer immune serum efficiently reduced the bacterial counts in the lungs during the early phase but not during the chronic phase. The proliferation of bacteria induced by CY treatment was not suppressed by the administration of the immune serum in either phase. When the mice were exposed to an aerosol containing Pseudomonas aeruginosa P9 in the chronic phase, the organisms from the secondary infection were eliminated from the lungs in the same manner as in the case of primary infection with P. aeruginosa. Thus, PMNs seem to play an important role in the suppression of bacterial proliferation in the early and chronic phases, and the specific antibody might have a supplementary effect on the defensive action of PMNs in the chronic phase. It is also presumed that the bacteria in the chronic phase of infection are sequestered at sites hardly accessible to PMNs. PMID- 1753883 TI - Electron microscopic studies on the in vitro proliferation of spotted fever group rickettsia isolated in Japan. AB - Rickettsia was isolated from a patient with Japanese spotted fever, and its proliferation in cultured green monkey kidney cells was observed by electron microscopy. In the course of this study, we observed fusion of infected cells to uninfected cells which may be a way of spreading the rickettsiae from a cell to another. On the other hand, whirlpool-like, multilayer membranous structures, similar to the mesosomes of gram-negative bacteria, were sometimes seen in the rickettsial cells. The other profiles common to the other rickettsiae in spotted fever group were observed, such as the electron-lucent halo zone around the rickettsiae, and external fibrous materials on their surface, but intranuclear multiplication was rarely observed. PMID- 1753884 TI - Relative ability of distinct isotypes of human major histocompatibility complex class II molecules in binding staphylococcal enterotoxin A. AB - Relative ability of distinct isotypes of human major histocompatibility complex class II molecules to bind staphylococcal enterotoxin A (SEA) was investigated. SEA-binding was observed in L cells transfected with DR2 and DQw1 genes. By contrast, it was not detected in L cells transfected with DPw4 and DP (Cp63) genes. All the transfectants supported SEA-induced IL-2 production by human T cells. Levels of the accessory activity were low in the DPw4 and DP (Cp63) transfectants compared with the DR2 and DQw1 transfectants. In view of the observation that all the transfectants express well the transfected gene products on their surface, the results indicate that DR and DQ molecules bind SEA with high affinity, while DP molecules bind it with fairly low affinity. PMID- 1753885 TI - [Complexes of soil micromycetes in the area of the influence of the Chernobyl Atomic Electric Power Station]. AB - Complexes of soil micromycetes in the Chernobyl 30-km zone of the Ukrainian Polesye were studied for 1986-1989 with regard for such ecological parameters as the level of radiation contamination, a particular observation site, depth of soil horizon and season. As a result of the study correlation pleiads of soil micromycete complexes have been revealed with their structure and fungal genera characteristic of such complexes determined. The overwhelming majority of correlation pleiads of fungal complexes are attributed to complex-organized ones and this indicated high radioresistance of mycobiota in the studied, soils. Melanine-containing genera of fungi rank among the first in formation of correlation pleiads of soil micromycete complexes. PMID- 1753886 TI - [The stability of the alkylating derivatives of oligodeoxyribonucleotides containing a cholesterol or phenazine radical added to the 3'-termination during their interaction with Acholeplasma laidlawii PG-8]. AB - Stability of alkylating derivatives of decathymidylates protected on the 3' terminal by cholesterol and phenazine residues has been studied in the process of their interaction with cells of Acholeplasma laidlawii PG-8. It is shown that the studied reagents are not split by nucleases of A. laidlawii PG-8 for the time necessary for alkylation of mycoplasma biopolymers. PMID- 1753887 TI - [The interaction of alkylating derivatives of oligodeoxyribonucleotides and their methylphosphonate analogs with Mycoplasma cells]. AB - Alkylating derivatives of decathymidylates and methylphosphonate analogs of oligodeoxyribonucleotides (MPAO) were studied for their interaction with cells of Acholeplasma laidlawii PG-8, Mycoplasma capricolum California Kid, M. pneumoniae FH and phytopathogenic strain (St. 118). It is shown that MPAO of octa- and hexadecathymidylates as well as decathymidylates 3'-terminal modified by phenazine and cholesterol groupings are sorbed by mycoplasma cells and can penetrate inside the cells. Efficiency of binding of alkylating derivatives and MPAO with mycoplasma cells depends on interaction time of reagents, their concentration in the reaction mixture and temperature. PMID- 1753888 TI - [The selection of the composition of the medium for optimizing the amine synthetic activity of aerobic bacilli]. AB - Nutrient medium chosen as a basic one after preliminary test of several media known from literature has been optimized to intensify biosynthesis and amine nitrogen production by three strains of aerobic sporulating bacteria to culture liquid. The method of mathematical planning used in the experiments has permitted obtaining the components ratio for the medium on which production of amine nitrogen to the environment increased 2.3-3.2 times. The best variants of the optimized medium promoted an increase of the aminosynthetic activity of the studied bacteria by more than 320%. The obtained nutrient medium is appropriate for a wide screening of aerobic bacilli for their ability to synthesize amino compounds. PMID- 1753889 TI - [The interaction of soil micromycetes with "hot" particles in a model system]. AB - A model system which permits observing for a long time and fixing interaction of fungi with a radiation source has been created on the basis of an isolated "hot" particle, deficient mineral medium (saccharose content 60 mg/l) and suspension of fungal conidia. Five species (six strains) of micromycetes isolated from radionuclide-contaminated soils and fifteen "hot" particles have been tested. It has been found out for the first time that Cladosporium cladosporioides and Penicillium roseo-purpureum are able actively overgrow "hot" particles whose radioactivity did not exceed 3.1-1.0(-7) Ci by gamma-spectrum and to destroy them 50-150 days later. Certain changes in morphology of fungi-destructors of "hot" particles are revealed. A problem on ecological significance of the found phenomenon is discussed. PMID- 1753890 TI - Elements of microdosimetry. AB - This is an introductory tutorial to the field of microdosimetry. Following a brief historical outline, we review the physics of experimental and theoretical microdosimetry and the application of microdosimetry to radiation biology within the so-called "site" approximation. Modern interpretations of microdosimetry that make use of methods developed in integral geometry are described under the heading "structural microdosimetry;" this also illustrates the conceptual basis of dual radiation action. A discussion concerning some future prospects of this field concludes the review. PMID- 1753891 TI - The effect of patient motion on dose uncertainty in charged particle irradiation for lesions encircling the brain stem or spinal cord. AB - A specialized charged-particle radiotherapy technique developed at Lawrence Berkeley Laboratory (LBL) is applied to patients with lesions abutting or surrounding the spinal cord or brain stem. This technique divides the target into two parts, one partially surrounding the critical structure (brain stem or spinal cord) and a second excluding the critical structure and abutting the first portion of the target. Compensators are used to conform the dose distribution to the distal surface of the target. This technique represents a novel approach in treating unresectable or residual tumors surrounding the spinal cord or brain stem. Since the placement of the patient with respect to beam-shaping devices is critical for divided-target treatments, a method for calculating dose distributions reflecting random patient motion is proposed, and the effects of random patient motion are studied for two divided-target patient examples. Dose volume histograms and a normal-tissue complication probability model are used in this analysis. For the patients considered in this study, the normal-tissue complication probability model predicts that random patient motion less than or equal to 0.2 cm is tolerable in terms of spinal cord complications. PMID- 1753892 TI - Investigation of an FFT-based correlation technique for verification of radiation treatment setup. AB - Electronic portal imaging devices that capture an image of a patient's treatment field electronically by means of a computer data acquisition system operating in real time are becoming available. This paper reports on a study of a field verification correlation algorithm that can compare each treatment portal image to an image of the correct treatment field positioning. The algorithm requires no human intervention or analysis of the images but rather uses fast Fourier transforms to produce a correlation distribution. The position and amplitude of the correlation distribution maximum were tested as objective measures of translational and rotational differences of subject positions between pairs of images. The concept was tested by using a prototype algorithm to obtain the correlation distributions for images of an Alderson Rando head phantom. Images of the phantom setup with various errors were compared with an image of the phantom in the initial, correct treatment position. Translations, in-plane and out-of plane rotations, and combinations of translations and rotations were studied. The algorithm accurately measured translations. The value of the correlation distribution maximum was found to be a reasonable candidate for an alignment parameter for which tolerable error thresholds might be established. PMID- 1753893 TI - Improvement of precision in spatial localization of radio-opaque markers using the two-film technique. AB - Radio-opaque markers implanted inside or placed on the skin of patients can be used to detect set-up errors and patient motion. The effects of imaging geometry accuracy for standard radiotherapy equipment on the precision of calculating the positions of radio-opaque spherical markers using two orthogonal radiographic film projections is investigated. Inaccuracies in the imaging geometry are computed from the manually digitized positions of the marker images on each film pair. Actual marker locations are calculated with a precision limited only by the variance in manual digitization by incorporating those imaging geometry inaccuracies into their computation. Results of a phantom study using a grid of markers in a plastic block indicate that submillimeter precision can be obtained for the spatial coordinates of individual markers, and that the precision is not sensitive to the small inaccuracies in imaging geometry present within the mechanical tolerances of modern radiotherapy treatment machines and simulators. PMID- 1753894 TI - Image restoration of digital radiography using dual sensor Wiener filter. AB - A dual sensor Wiener filter (DSWF) technique was used to improve the image quality of a scanning type digital radiographic system. In a digital radiographic system, image quality is evaluated by resolution and SNR (signal-to-noise ratio), which are two important parameters representing the objective performance of the system. In this method, when two images are acquired in the same region using two sensors with different characteristics of resolution and SNR, they are processed simultaneously using DSWF, which is the extended concept of a Wiener filter to two dimensions. DSWF uses the cross power spectrum between dual sensor outputs of the same chest radiographic image in the design of filter parameters. It has been implemented with fast algorithm using FFT (fast Fourier transform). The performance of the proposed method is compared with that of conventional methods (Wiener filter and parametric projection filter). In simulation studies, it is shown in 12 cases that this new method has SNR improvement of 1-2 dB better than conventional methods. PMID- 1753895 TI - Transfer function measurement and analysis for a magnetic resonance imager. AB - The transfer function characteristics of a 1.5T imager have been determined. An edge response function (ERF) was obtained from a water/Plexiglas interface at various pixel widths ranging from 0.312 to 1.0 mm. An SE pulse sequence was used with a 5-mm transaxial slice. The ERF was smoothed, differentiated, and Fourier transformed to obtain MTF curves. The LSF was analyzed for skewness and kurtosis. The area under the MTF amplitude curves and the equivalent bandpass were calculated. All ERFs, LSFs, and MTFs were well behaved. The resulting LSF was Gaussian. All calculated MTFs had cutoff frequencies slightly less than the theoretical Nyquist limit. The MTF calculated from the theoretical Gaussian LSF is slightly superior to that calculated from experimental data and provides an upper limit to the MTF. Spatial resolution in our MR imager is dominated by the pixel size via the Nyquist sampling theorem. System performance is slightly less than theoretically predicted, possibly due to image processing algorithms during the reconstruction process. PMID- 1753896 TI - Accurate characterization of image intensifier distortion. AB - Image intensifier distortion due to photocathode curvature and electron optics is shown to be approximated by a simple two parameter odd-power polynomial. The accuracy of this fit was found to be far better than that of two other one parameter characterizations of distortion when applied to experimental data from four different model image intensifiers ranging in diameter from 9 to 14 in. The standard errors of the two parameters fits were less than 0.1 mm or 0.03% of the field of the IIs and were within the estimated measurement error. PMID- 1753897 TI - The lens coupling efficiency in megavoltage imaging. AB - In TV-based megavoltage imaging systems it is useful to be able to estimate the geometrical efficiency g2 of the camera lens. It is shown that the appropriate expression is g2 = (16n2)-1 X [F(1 + 1/m)]-2, where n is the refractive index of the scintillator, F is the F-number of the lens and m is the optical magnification. This expression yields estimates for g2 that are 5 to 10 times smaller than the estimates that have appeared previously in the literature. PMID- 1753898 TI - Survey of tissue-air ratio data: a review of the literature for diagnostic radiology. PMID- 1753899 TI - The role of nonlinear ultrasound propagation during hyperthermia treatments. AB - In this study the feasibility of utilizing nonlinear ultrasound propagation to control the power deposition patterns during ultrasound hyperthermia treatments of malignant tumors was investigated. From the in vivo results it appears that the power deposition pattern and the temperature distributions can be significantly altered by increasing the temporal peak power of the source while reducing the duty cycle to maintain the same acoustic time average power. The maximum temperature gains obtained during hyperthermia sonication (between 1.5 and 2) were significantly less than one could obtain by varying the frequency and the other parameters of transducers and thus, the linear characteristics of the ultrasound fields should be used when hyperthermia systems are designed and treatments are planned. Then during the treatment nonlinear propagation can be used to provide on-line control of the power deposition patterns. The transducer characteristics determined the magnitude of the temperature gain and the nonlinear propagation region could not be reached when sharply focused (F number = 1) transducers were used at the frequencies between 0.25 to 1.68 MHz due to the high pressure amplitudes that exceeded the transient cavitation threshold. PMID- 1753900 TI - Heating patterns of microwave applicators in inhomogeneous arm and thigh phantoms. AB - Heating rate (HR) patterns in cylindrical structures were studied with inhomogeneous limb phantoms. These phantoms, arm and thigh models consisting of fat, bone, and muscle material, were heated with Clini-Therm L, M, and MS applicators at 915 MHz. The thigh model is 18 cm in diameter with 2.65-cm-thick fat on the outside and a 4-cm-diam bone in the center. The arm model is 9 cm in diameter with 1.35-cm-thick fat and 2-cm-diam bone. All models are 29 cm long with phantom muscle in the space between fat and bone and were heated with their long axes parallel or perpendicular to the E field. HR patterns in the transverse and longitudinal planes were obtained thermographically. A large water bolus, with the water channels parallel to the E field, was used in every case. In the thigh model, maximum heating was in the muscle for both L and M applicators when the E field was parallel to the long axis. When it was perpendicular, the maximum heating occurred in the fat layer. However, the peak HR in the fat remained about the same for both E field orientations. For the small applicator, heating was mostly in the fat, and the two field orientations did not cause much difference in the heating pattern. In the arm model, the maximum heating of all three applicators occurred mostly in the muscle for both E-field orientations. However, the maximum HR was reduced by a factor of 2 to 3 when the E field was perpendicular rather than parallel to the long axis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753901 TI - Ultrasound focal lesion detectability phantoms. AB - Two phantoms for assessing the performance of ultrasound scanners regarding detectability of small focal lesions are described. The spherical simulated lesions in the phantoms have diameters of 2.4, 3.0, and 4.0 mm and backscatter coefficients which are 16, 9, and 6 dB below that of the surrounding tissue mimicking material, the latter simulating normal tissue such as liver. Random positioning and relatively large numbers of lesions deal with the statistical problem related to mistaking a normal textural fluctuation, characteristic of ultrasound images of parenchymal tissue, to be a small lesion. All lesions have ultrasonic properties that are the same as those of the surrounding material except for the backscatter coefficient; therefore, artifacts resulting from attenuation, reverberation, and/or refraction are absent, and detectability of deeper lesions is not influenced by the presence of more proximal ones. A method is outlined for using the phantoms to determine bounding proximal and distal depths of resolution, or detectability, of focal lesions of a given object contrast and size. Tests for observer dependence involving five subjects resulted in standard deviations in the distal and proximal depths of less than 0.5 cm. A repeat of the observer dependence tests 18 months later showed little change in the results. In addition, results obtained by two experienced observers are also given for a variety of specific scanners, scanning heads, and scanning parameters. PMID- 1753902 TI - Dose distributions in regions containing beta sources: uniform spherical source regions in homogeneous media. AB - The energy-averaged transport model for the calculation of dose rate distributions is applied to uniform, spherical source distributions in homogeneous media for radii smaller than the electron range. The model agrees well with Monte Carlo based calculations for source distributions with radii greater than half the continuous slowing down approximation range. The dose rate distributions can be written in the medical internal radiation dose (MIRD) formalism. PMID- 1753903 TI - Dose distributions in regions containing beta sources: irregularly shaped source distributions in homogeneous media. AB - Methods are introduced by which dose rate distributions due to nonuniform, irregularly shaped distributions of beta emitters can be calculated using dose rate distributions for uniform, spherical source distributions. The dose rate distributions can be written in the MIRD formalism. PMID- 1753904 TI - A sensitivity study of micro-TLDs for in vivo dosimetry of radioimmunotherapy. AB - The sensitivity and precision of teflon-imbedded CaSO4:Dy microthermoluminescent dosimeters (micro-TLDs) were determined. The micro-TLDs were sectioned from miniature TLDs (200 microns x 400 microns x 5 mm) that were fabricated using standard techniques. In order to measure absorbed dose, the miniature TLDs can be implanted directly into tissues (e.g., tumor xenografts) that have received injections of radiolabeled monoclonal antibodies. Micro-TLDs recovered from tissue sections cut with a microtome can be read out to determine local absorbed dose. The precision of dose estimation was quantified for uniformly irradiated 32 , 96-, and 192-microns TLD chips; coefficients of variation ranged from 22% to 41%, depending on chip size. The coefficients of variation were reduced to less than 12% using individual relative sensitivity factors for each micro-TLD. The spatial resolution of the micro-TLDs was studied by placing miniature TLDs across the sharp penumbral region of a linear accelerator x-ray field. TLDs were sectioned into 32-microns chips which were read out to determine the relative absorbed dose. The sharpness of the penumbra was readily quantified by the micro TLDs. PMID- 1753905 TI - Dose-volume considerations with linear programming optimization. AB - A method of incorporating dose-volume considerations within the framework of conventional linear programming is presented. This method is suitable for the optimization of beam weights and angles using a conformal treatment philosophy (i.e., tailoring the high-dose region to the target volume only). Dose-volume constraints are introduced using the concept that volumes of normal tissue nearer the target volume will be allowed higher dose constraints than volumes of normal tissue distal to the target volume. Each involved normal structure is divided into high-dose and low-dose volumes. These two volume partitions are represented by constraint points with either high-dose or low-dose constraints, respectively. Optimized treatment plans for three clinical sites demonstrate that this technique meets or surpasses the original dose-volume constraints for a conformal type treatment plan using straightforward linear programming in a time frame that is comparable to other linear programming problems. PMID- 1753906 TI - Algorithm for dosimetry of multiarc linear-accelerator stereotactic radiosurgery. AB - Treatment planning for multiarc radiosurgery is an inherently complex three dimensional dosimetry problem. Characteristics of small-field x-ray beams suggest that major simplification of the dose computation algorithm is possible without significant loss of accuracy compared to calculations based on large-field algorithms. The simplification makes it practical to efficiently implement accurate multiplanar dosimetry calculations on a desktop computer. An algorithm is described that is based on data from fixed-beam tissue-maximum-ratio (TMR) and profile measurements at isocenter. The profile for each fixed beam is scaled geometrically according to distance from the x-ray source. Beam broadening due to scatter is taken into account by a simple formula that interpolates the full width at half maximum (FWHM) between profiles at isocenter at different depths in phantom. TMR and profile data for two representative small-field collimators (10- and 25-mm projected diameter) were obtained by TLD and film measurements in a phantom. The accuracy of the calculational method and the associated computer program were verified by TLD and film measurements of noncoplanar multiarc irradiations from these collimators on a 4-MV linear accelerator. Comparison of film measurements in two orthogonal planes showed close agreement with calculations in the shape of the dose distribution. Maximal separation of measured and calculated 90%, 80%, and 50% isodose curves was less than or equal to 0.5 mm for all planes and collimators. All TLD and film measurements of dose to isocenter agreed with calculations to within 2%. PMID- 1753907 TI - Calculation of water/air stopping-power ratios using EGS4 with explicit treatment of electron-positron differences. AB - Using the EGS4 Monte Carlo simulation program, a general purpose code has been written to calculate Bragg-Gray and Spencer-Attix stopping-power ratios for use in radiation dosimetry. The stopping-power ratios can be calculated in any material in any region in a general cylindrical geometry with a large number of source geometries possible. The calculations take into account for the first time the differences between the stopping powers and the inelastic scattering of positrons and electrons. The results show that previous calculations ignoring these effects were accurate. The present results agree, typically within 0.1%, with the Spencer-Attix water-to-air stopping-power ratios for broad parallel beams of electrons given in the AAPM and IAEA protocols except at the surface where the present calculations follow the buildup of secondary electrons in more detail and see a 2% reduction in the stopping-power ratios. PMID- 1753908 TI - A comparison of ionization-chamber and water-calorimeter dosimetry for high energy x rays. AB - The temperature-regulated, flexible, water calorimeter developed in the authors' laboratory was shown previously to yield a dose-to-water from 4-MV x rays that is in very close agreement with ionization measurements made in accordance with the AAPM dosimetry protocol. The range of beam energies for this type of comparison has been increased to include 60Co, and 4-, 6- and 25-MV x rays. The grand mean of the ratios of doses obtained from the calorimeter and ionization chamber, the Cal/Ion ratio, for the four beam energies studied is 1.001 +/- 0.001. As no significant trend with beam energy was detected, it is concluded that the calorimeter and ionization chamber yield equally accurate results. Because the calibration of the calorimeter depends solely upon the accuracy with which water temperatures in the range 2-10 degrees C can be measured, and dose is given by the product of the specific heat of water and the temperature change produced by irradiation, the water calorimeter has the potential to place radiation dosimetry on a much firmer foundation than presently exists. PMID- 1753909 TI - Results of photon absorbed-dose measurements using the AAPM TG-21 protocol for accelerating potentials up to 26 MV. AB - The AAPM Task Group 21 protocol for the calibration of high-energy photon and electron beams was produced to accomplish essentially two goals: (1) incorporate the latest physical data available for calculating absorbed dose from ionization measurements and (2) to eliminate inconsistencies in absorbed dose measurements made with various ion chamber and phantom combinations. The ability of the protocol was assessed to consistently determine x-ray absorbed dose from measurements made with four Farmer-type chambers and one parallel-plate chamber in water, polystyrene, and acrylic phantoms. The measurements were performed using seven high-energy x-ray beams from 60Co to 26-MV nominal accelerating potential. The absorbed dose to water calculated from measurements made with the various chamber and phantom combinations were found to be consistent. The doses calculated for the two most common phantom materials, water and polystyrene, were found to be in excellent agreement. This resolved a 1.6% discrepancy in the absorbed dose determined from the two phantoms using the SCRAD protocol. The doses for acrylic phantoms were found to be approximately 1.2%, low for nominal accelerating potentials less than 8.8 MV. For accelerating potentials of 8.8 MV or greater the agreement was considerably better. The mean dose determined for the parallel-plate chamber from measurements in polystyrene was found to be within 0.7% of the mean dose determined using Farmer-type ion chambers in all phantom materials. PMID- 1753910 TI - Measurement of the replacement correction factor for parallel-plate chambers in electron fields. AB - When parallel-plate chambers are used for dosimetry in electron fields, the AAPM dosimetry protocol recommends a value of 1.0 for the replacement correction factor, P(repl),pp,E, until further data become available. Here, P(repl),pp,E for five commercially available parallel-plate chambers was measured as a function of electron energy from a nominal value of 5.5 to 22 MeV by comparison with a cylindrical chamber whose P(repl),cyl,E was obtained from data in the protocol. Since this method is based on the concept of a constant value for Ngas,pp, the energy and modality dependence of Ngap,pp is also investigated for these chambers for Co-60, 4-, 6-, 24-MV photons and for 22-MeV electrons. It is found that for three of the chambers P(repl),pp,E is independent of energy, consistent with unity within one or two standard deviations (s.d.). For the fourth chamber P(repl),pp,E is similarly consistent with one above 10 MeV, but decreases at lower energies, while for the fifth one it shows a systematic drop with decreasing energy. PMID- 1753911 TI - Replacement correction (P(repl)) for ion chamber dosimetry. AB - The use of replacement correction when depth dose distribution is measured with a cylindrical ion chamber is discussed. A review of relevant data shows that the displacement of the effective point of measurement is an appropriate method to make replacement correction for the entire depth ionization curve. PMID- 1753912 TI - Tests of an electron monitor for routine quality control measurements of electron energies. AB - The depth dose for electrons is sensitive to energy and the AAPM Task Group 24 has recommended that tests be performed at monthly intervals to assure electron beam energy constancy by verifying the depth for the 80% dose to within +/- 3 mm. Typically, this is accomplished by using a two-depth dose ratio technique. Recently, a new device, the Geske monitor, has been introduced that is designed for verifying energy constancy in a single reading. The monitor consists of nine parallel plate detectors that alternate with 5-mm-thick absorbers made of an aluminum alloy. An evaluation of the clinical usefulness of this monitor for the electron beams available on a Varian Clinac 20 has been undertaken with respect to energy discrimination. Beam energy changes of 3 mm of the 80% dose give rise to measurable output changes ranging from 1.7% for 20-MeV electron beams to 15% for 6-MeV electron beams. PMID- 1753913 TI - Comparison of dose calibration by ionometric and chemical dosimetry for 6- and 45 MV x-ray beams. AB - This work reports the results of an experiment carried out to investigate the compatibility of TG-21 ion chamber calibration with Fricke dosimetry near the extremes of the clinically available megavoltage photon energy range. Doses determined from ion chamber measurements and from chemical dosimetry are compared for a 6-MV linear accelerator x-ray beam and 45-MV betatron beam. The Fricke dosimetry was carried out by the National Institute of Standards and Technology. Agreement within 1% between the two techniques was obtained at both photon energies using a currently accepted G-value. PMID- 1753914 TI - Central axis depth dose curve for electron beams. AB - In this article an analytical equation for electron depth dose is proposed electron energies from 6-20 MeV. The equation contains four parameters and it fits the build-up region, fall-off region as well as the bremsstrahlung background region. The calculated values from this equation fit within 1,5% of the measured data in the build-up region and in the fall-off region within 0,5 mm for the energy range 5-10 MeV and within 1 mm for the range 12-20 MeV. This equation can be applied beyond the practical range. PMID- 1753915 TI - A convolution algorithm for brachytherapy dose computations in heterogeneous geometries. AB - Currently-available brachytherapy dose computation algorithms ignore heterogeneities such as tissue-air interfaces, shielded gynecological colpostats, and tissue-composition variations in 125I implants despite dose computation errors as large as 40%. To calculate dose in the presence of tissue and applicator heterogeneities, a computer code has been developed that describes scatter dose as a 3-D spatial integral which convolves primary photon fluence with a dose-spread array. The dose-spread array describes the distribution of dose due to multiple scattering about a single primary interaction site and is precomputed by the Monte Carlo method. To correct for heterogeneities traversed by the primary photons, the dose-spread array is renormalized to reflect the density and composition of the element, and the distance to the point of interest is scaled by the path-length of the intervening medium. Convolution calculations for 125I and 137Cs point sources in the presence of finite phantoms, air voids and high-density shields have been compared to the corresponding Monte Carlo calculations. The convolution code absolute and relative dose rate predictions are shown to agree with Monte Carlo calculations within 3%. Direct evaluation of the 3-D spatial convolution integral using 1-D adaptive integration reveals efficiency gains of 20-50 relative to Monte Carlo photon-transport calculations. PMID- 1753916 TI - Scattering effects on the dosimetry of iridium-192. AB - Dosimetry calculations for iridium-192 sources generally assume that a sufficient medium surrounds both the iridium source(s) and the point of calculation so that full scattering conditions exist. In several clinical applications the iridium sources may be anatomically located so that the full scattering requirement is not satisfied. To assess the magnitude of this problem, relative measurements were made with a small ionization chamber in phantoms near air and lung equivalent interfaces. Dose reduction caused by decreasing the volume of scattering material near these interfaces was then evaluated for a few clinical applications. The results show that reductions on the order of 8% may be expected at the interface with minimal dose reduction within the volume of the implant itself. In addition, the results indicate the verification of source strength of iridium sources in phantom require phantom dimensions determined by the source chamber separation distance. PMID- 1753917 TI - Role of potassium in the pathogenesis of acute renal failure. AB - Potassium depletion can potentiate several experimental models of acute renal failure. It causes renal vasoconstriction, probably under the influence of vasoconstrictor prostaglandins and angiotensin II, and causes a reduction in vasodilatory prostaglandins. Aminoglycoside nephrotoxicity in experimental animals and in man causes a reduction in serum potassium and in animals it enhances the functional and histological damage produced by aminoglycosides. Chronic potassium loading protects against mercuric chloride, uranyl nitrate, and gentamicin models of acute renal failure. In the gentamicin model, protection is associated with a stimulation of renal cortical Na-K-ATPase activity and a reduction in the level of gentamicin accumulated in cortical tissue. In the clinical setting, potassium deficiency should be avoided in patients at risk for acute renal failure. However, potassium loading should also be avoided, since a falling glomerular filtration rate in the presence of a potassium load could result in potentially serious hyperkalemia. PMID- 1753918 TI - Calcium and acute renal failure. AB - Tubular cell calcium concentration and content rise following acute renal injury induced by ischemic and toxic insults. Since calcium plays a critical role in many cell functions and the proximal tubule appears to be a major site of injury in acute renal failure, it is possible that cell calcium overload plays a direct role in the pathogenesis of acute renal failure. Tubular cell calcium overload has been associated with altered function at the level of the plasma membrane, mitochondria, endoplasmic reticulum and cytoskeleton. While there is evidence to support a role for calcium in acute renal injury, the importance of cell calcium overload needs to be further explored. Furthermore, alterations in extracellular calcium and mineral metabolism may be involved in some aspects of acute renal failure and recovery. Calcium channel blockers and other interventions designed to modulate calcium changes may have a role in the treatment of acute renal failure. PMID- 1753919 TI - The role of phosphate in the potentiation or amelioration of acute renal failure. AB - Alterations in the balance of several cations have been shown to affect the severity of acute renal failure. It has been suggested in both clinical and experimental studies that changes in phosphate balance can markedly potentiate as well as ameliorate the renal dysfunction seen in both acute and chronic nephropathies. To determine the role phosphate plays in the course of gentamicin induced acute renal failure, we examined rats maintained on control, phosphate supplemented, and phosphate-depleted diets. In both control and phosphate supplemented groups of rats, the degree and severity of gentamicin-induced acute renal failure was similar. By contrast, renal function was better preserved in the phosphate-depleted group. Furthermore, morphologic evaluation revealed a significantly lower number of necrotic proximal tubule cells in phosphate depleted rats when compared to the control or phosphate-replete rats. Renal cortical gentamicin concentrations were not different between the phosphate depleted and phosphate-supplemented groups. We conclude that phosphate depletion is protective against nephrotoxicity. This effect appears to be independent of alterations in serum calcium, urinary calcium excretion and renal cortical gentamicin concentration. PMID- 1753920 TI - Acid-base balance and acute renal failure. AB - In several models of acute renal failure (ARF) in animals, acidosis has been found to worsen the renal failure, whereas alkalosis may ameliorate it. Most evidence points to a reduction in the degree of tubular obstruction by casts as the explanation for the beneficial effects of bicarbonate administration. However, alkalinization of the urine is effective only in some experimental conditions but not in others. The reason for these differences is not known but may relate to the nature of the obstructing casts. Alkalinization of the urine could decrease cast formation in Bence-Jones protein and hemoglobinuric ARF by increasing the negative charge on these molecules, thereby diminishing precipitation with anionic Tamm-Horsfall protein. In contrast, release of tubular cell contents into the urine, as occurs in renal ischemia, could lead to complex casts not responsive to alterations in urine pH. In aminoglycoside ARF, the beneficial effects of urine alkalinization may be due primarily to reduced uptake of the antibiotic by tubular epithelium, resulting in less cellular damage. Because tubular obstruction reduces net filtration pressure, new approaches to therapy which include efforts to raise net glomerular filtration pressure may improve the therapeutic efficacy of alkali administration. PMID- 1753921 TI - Oxygen free radicals in acute renal failure. AB - Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused by restoration of blood flow when oxygen free radicals are produced. Cellular sources of oxygen free radicals include the electron transport chain, the microsomal electron transport chain, oxidant enzymes (xanthine oxidase, cyclo-oxygenase), phagocytes, and cellular auto-oxidation of Fe2+ and epinephrine. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy production. Studies in models of acute renal failure have yielded convincing evidence that oxygen free radical production occurs during ischemia/reperfusion. More than a dozen reports have demonstrated the ability of exogenous antioxidants to ameliorate renal injury in vivo. Direct demonstration of increased oxygen free radical production during reoxygenation following hypoxia has been shown in cultured renal epithelial cells. Oxygen free radicals also play a role in toxic acute renal failure. The therapeutic usefulness of free radical scavengers remains to be tested. PMID- 1753922 TI - Electrolyte abnormalities before and after the onset of acute renal failure. AB - The chemical composition of body fluids, which is regulated by the kidneys, may affect renal function. Conversely, the onset of acute renal failure (ARF) interrupts the normal regulation of the volume and content of the body fluids. In order to further study these relationships and determine the epidemiology and consequences of ARF in a tertiary-care setting, the computerized hospital data base was used to identify and obtain laboratory data on patients with ARF. 9,276 patients, encountered over a 90-day period, were surveyed and 96 were found to have developed ARF in the hospital (3.1% of admissions). The majority of the patients with ARF were found on the medicine service (68%), and sepsis with aminoglycoside use was the single most common of multiple etiologic factors. Patients with ARF experienced an increase in morbidity, as evidenced by an increase in the hospital length of stay and frequent need for ICU care. Mortality (29%) was due to the patients' underlying illnesses, and not uremia. Serum levels of the electrolytes prior to the onset of ARF were within the normal range with the exception of the creatinine (2.04 +/- 0.25 mg/dl) and bicarbonate (22.9 +/- 0.6 meq/l). After the development of ARF (mean creatinine 3.91 +/- 0.03) sodium, chloride, and bicarbonate were decreased, and phosphate, uric acid, and the anion gap were increased (p less than 0.05 for all values). The decrease in serum calcium became significant (p less than 0.05) in those patients whose creatinine increased by a factor of 2 or more. PMID- 1753923 TI - Structural correlates of renal electrolyte alterations in acute renal failure. AB - In this review, structural and ultrastructural alterations in the kidney in acute renal failure are described and illustrated in some detail. Morphologic findings in clinical and experimental acute renal failure of the type produced by ischemia and some nephrotoxins, so-called 'acute tubular necrosis' are compared and discrepancies between findings in clinical specimens and experimental models noted and discussed. Since perturbations in intrarenal electrolyte species almost surely play a major pathogenic role in renal injury and dysfunction, correlations between altered intrarenal electrolyte transport and abnormal cellular ion concentrations, and morphologic alterations are emphasized in this review. PMID- 1753924 TI - Role of the sodium ion in acute renal failure. AB - Acute renal failure (ARF), an abrupt decline in renal function in its simplest terms, continues to elude precise pathophysiologic definition in human as well as experimental models. In the setting of ischemic or toxic renal injury, the role of sodium chloride as the major constituent of extracellular fluid volume (ECFV) is critically important in the maintenance of renal blood flow. Renal perfusion can be severely curtailed in states of ECFV depletion by activation of the renin angiotensin axis leading to profound intrarenal hemodynamic alterations. This review will discuss evidence for the role of sodium chloride in the pathogenesis and modification of ischemic and toxic ARF. Much of the data arises from studies in experimental animal models of human disease. The results of clinical studies will be emphasized when available. PMID- 1753925 TI - [The lamina limitans. Its scanning electron microscopic aspects]. AB - Many researches agree in maintaining that all the membraneous structure visible in the most external parts of the dental tubules must be considered not ad cytoplasmatic membranes of the odontoblastic processes but as an extracellular organic matrix which in certain conditions may appear detached from the internal wall of the tubule and simulated a superimposable aspect like that of an odontoblastic extension. The aim of this study was to examine at the SEM the state of this organic component in normal conditions and after demineralization with citric acid. Therefore the entire teeth of young people were fixed in formalin and dissected by fracturing. Some of the samples were demineralized with a citric acid solution. All the samples were dehydrated and metallized for the observation at SEM. Demineralization made the peritubular dentine disappear and expose inside every tubule a sheet-like structure which extended all along the tubules. The samples which were not demineralized did not demonstrate a similar structure because of their tight adhesion to the internal wall surface. This kind of formation which other researchers calls "lamina limitans" because of its high content of glycosaminoglycans might be a key factor in controlling the formation of peritubular dentine and tubular sclerosis and it will surely lead to further interesting research. PMID- 1753926 TI - [A histological study of hard dental tissues in nondecalcified sections using the cutting-grinding technic]. AB - With the cutting-grinding technique (Exakt System) it is possible to obtain sections with a width of less than 10 microns of specimens such as teeth, crowns, bridges, implants, mineralized structures, which cannot be cut with routine histological techniques. In the present paper the authors study the efficacy of this technique in hard dental tissues. PMID- 1753927 TI - [Oral lesions and intestinal pathology]. PMID- 1753928 TI - [The effect of orthodontic magnets on the oral microbial flora]. AB - In this study we wanted to test the in vitro effects of orthodontic magnetic brackets, developing different magnetic fields, on the oral microbial flora. We noticed that a magnetic field has its most considerable influence on Candida albicans growth; the stimulating response depends on various factors: cell inoculum, exposure time and magnetic field frequency. PMID- 1753929 TI - [Aneurysmal cysts of the jaws. The nosological picture and a clinical case report]. AB - After discussing the classification of aneurysmatic cyst with particular reference to its characteristics for differential diagnosis with other pathologies of various origin, a personal case is reported. The diagnosis and treatment protocol of the clinical case in question is presented together with clinico-therapeutic problems and the results obtained with the diagnostic and therapeutic aids used. PMID- 1753930 TI - [Peripheral facial paralysis and HIV infection]. AB - Two cases of peripheral facial paralysis associated with infection by the human immunodeficiency virus in young intravenous drug abuser patients are reported. One patient manifested AIDS-related complex (ARC) and the other fulfilled the Center for Disease Control (CDC) criteria for AIDS. Clinical symptoms and signs occurred as facial paralysis and headache. One patient presented progressive motor slowing and the computerized tomography (CT) of the brain showed a wide hypodense lesion in the left temporal-anterior region and the involvement of the left basal ganglia. In this patient the impairment of the facial nerve was associated with a HIV-related encephalitis. In the second patient the CT did not show cerebral lesions and the etiology of the paralysis was unknown. PMID- 1753931 TI - [Aggressive ulcerous stomatitis due to the herpes simplex virus in an allogeneic bone marrow transplant. A clinical case]. AB - Aggressive ulcerative HSV stomatitis was observed in a patient 10 months after allogeneic bone marrow transplantation. The patient was affected by acute myeloid leukemia (LMA) in second remission and, after bone marrow transplantation, supported a severe graft versus host disease. Intravenous acyclovir was administered during 22 days and ulcerative stomatitis completely healed. PMID- 1753932 TI - [A case report of a true median cleft of the upper lip with a pedunculated median skin-mucosa mass]. AB - The Authors report an unusual case of median cleft of the upper lip with pedunculated skin and muscle contracting mass. About one hundred cases of true median cleft lip have been reported, only six showing a median pedunculated mass. As the embryogenesis of this malformation is still not completely clear, we think that any case with this characteristic has to be described. Besides the usual characteristic of the median "hare lip" this case shows a big egg-like pedunculated mass in which muscular tissue has been found well represented, and a wide incomplete maxillary cleft. PMID- 1753933 TI - [A chondroameloblastic embryoma of the jaw. A case report]. AB - A case of chondro-ameloblastic embryoma, on the posterior third of the palatine bone is reported. The report emphasises the importance of the neuromesenchymal origin of the ameloblastic cells and cartilaginous, fibro-connective and fibro myxoid tissue, that usually form the structure of the neoplasm. PMID- 1753934 TI - [The functional and surgical rehabilitative treatment of cleft lip and cleft palate in a case of the syndrome of the deletion of the long arm of chromosome 18 diagnosed in utero]. AB - Following an introductory illustration of the clinical characteristics of the 18q syndrome (De Grouchy syndrome), the paper describes the treatment carried out in a young patient with harelip and cleft palate in addition to chromosomopathy. Although the facial malformation and the karyotype with the deletion of a portion of the long arm of chromosome 18 were diagnosed in utero, the parents, having been correctly informed of the mental retardation usually associated with this syndrome and the possibility of surgical correction of the facial malformation, decided not to abort. The case offers an occasion for analysing the various stages and results obtained to date using a multi-specialised diagnostic approach and functional and surgical treatment of the harelip and cleft palate which have enabled much of the congenital handicap to be corrected. PMID- 1753935 TI - [Extracranial cephalic neurogenic tumors. A case report of a schwannoma with a rare location]. AB - Following a brief critical review of the latest international literature, the paper describes a case of extracranial cephalic neurogenic tumour in an unusual location. Clinical and anatomo-pathological aspects are assessed and the problems of therapy are discussed. PMID- 1753936 TI - [Linear and volumetric calculations of the free gingiva on deciduous and permanent teeth]. AB - The authors expose the results of an analysis made by measurements and volumetric calculations, of deciduous and permanent teeth, estimated at the level of the cementum-enamel junction and of the circumferences passing through the points of the occlusal and apical maximum convexity of the junction itself. It may be useful to remember free gingiva is that part of gingival sulcus included between the gingival margin and the bottom of sulcus, it is a tridimensional structure, having triangular section, where the gingival sulcus depth is the height and the thickness at the bottom of gingival sulcus is the base of the triangle. These measurements can be useful to examine closely the analysis of periodontal physiopathology. PMID- 1753937 TI - [The preliminary results of research on salcatonin treatment in the surgical therapy of jaw cysts]. AB - The results of research concerning a local and systemic treatment with salcatonin in surgical therapy of maxillary cysts are reported. A reduction in bone recovery time has been noted in the cases studied; this means a reduction in osteolytic area and a roentgenographic opacification of the same. PMID- 1753938 TI - [Our experience in the correction of a short frenulum labialis by Z-plasty]. AB - The authors report their experience of the reconstruction by z-plasty in cases of shortness of the lip frenum. Amongst several techniques they used for this correction they got best results utilizing a z-plasty, with wide flaps, planned so that after the transposition of the flaps the medial branch of the z-plasty falls horizontally into the deeper vestibular fornix. In all cases treated by that z-plasty the A. obtained a widening of the adherent part of the gingiva, deepening of the vestibulum, no recurrence of the shortness was observed. PMID- 1753939 TI - Intergeneric somatic hybridization in Gramineae: somatic hybrid plants between tall fescue (Festuca arundinacea Schreb.) and Italian ryegrass (Lolium multiflorum Lam.). AB - Tall fescue (Festuca arundinacea Schreb.) protoplasts, inactivated by iodoacetamide, and non-morphogenic Italian ryegrass (Lolium multiflorum Lam.) protoplasts, both derived from suspension cultures, were electrofused and putative somatic hybrid plants were recovered. Two different genotypic fusion combinations were carried out and several green plants were regenerated in one of them. With respect to plant habitus, leaf and inflorescence morphology, the regenerants had phenotypes intermediate between those of the parents. Southern hybridization analysis using a rice ribosomal DNA probe revealed that the regenerants contained both tall fescue- and Italian ryegrass-specific-DNA fragments. A cloned Italian ryegrass-specific interspersed DNA probe hybridized to total genomic DNA from Italian ryegrass and from the green regenerated somatic hybrid plants but not to tall fescue. Chromosome counts and zymograms of leaf esterases suggested nuclear genome instability of the somatic hybrid plants analyzed. Four mitochondrial probes and one chloroplast DNA probe were used in Southern hybridization experiments to analyze the organellar composition of the somatic hybrids obtained. The somatic hybrid plants analyzed showed tall fescue, additive or novel mtDNA patterns when hybridized with different mitochondrial gene-specific probes, while corresponding analysis using a chloroplast gene specific probe revealed in all cases the tall fescue hybridization profile. Independently regenerated F. arundinacea (+) L. multiflorum somatic hybrid plants were successfully transferred to soil and grown to maturity, representing the first flowering intergeneric somatic hybrids recovered in Gramineae. PMID- 1753940 TI - Subfamilies of serine tRNA genes in the bovine genome. AB - A bovine tRNA gene cluster has been characterized and the sequences of four tDNAs determined. Two of the tDNAs could encode tRNA(SerIGA), one tRNA(SerUGA), and the fourth tRNA(GlnCUG). The three serine tDNAs representing the UCN codon isoacceptor family are almost identical. However, the sequence of the tDNA(SerTGA) differs from a previously sequenced bovine tDNA(SerTGA) at 12 positions (ca. 14%). This finding suggests that in the bovine genome, two subfamilies of genes might encode tRNA(SerUGA). It also raises the possibility that new genes for a specific UCN isoacceptor might arise from the genes of a different isoacceptor, and could explain previously observed differences between species in the anticodons of coevolving pairs of tRNAs(SerUCN). The gene cluster also contains complete and partial copies, and fragments, of the BCS (bovine consensus sequence) SINE (short interspersed nuclear element) family, six examples of which were sequenced. Some of these elements occur in close proximity to two of the serine tDNAs. PMID- 1753941 TI - Construction of expression vectors based on the rice actin 1 (Act1) 5' region for use in monocot transformation. AB - It has been previously reported that the 5' region of the rice actin 1 gene (Act1) promoted high-level expression of a beta-glucuronidase reporter gene (Gus) in transformed rice cells. In this paper we describe the construction of Act1 based expression vectors for use in monocot transformation. As part of the development of these vectors, we have evaluated the influence of the Act1 first intron, the Act1-Gus junction-encoded N-terminal amino acids, and the sequence context surrounding the Act1 and Gus translation initiation site on Act1-Gus gene expression in rice and maize cells. We have found that addition of Act1 intron 1 to the transcription unit of a Gus reporter gene under control of the cauliflower mosaic virus (CaMV) 35S promoter stimulated GUS activity more than 10-fold in transformed rice cells. Optimization of the sequence context around the Gus translation initiation site resulted in a 4-fold stimulation of Gus expression in transformed rice cells. By utilizing both the Act1 intron 1 and optimized Gus translation initiation site, a 40-fold stimulation in Gus expression from the CaMV 35S promoter has been achieved in transformed rice cells; very similar results were obtained in transformed maize cells. Taken together these results suggest that the Act1-based expression vectors described here should promote the expression of foreign genes in most, if not all, transformed monocot cells to levels that have not previously been attainable with alternative expression vectors. PMID- 1753942 TI - Molecular characterization of new group A streptococcal bacteriophages containing the gene for streptococcal erythrogenic toxin A (speA). AB - Bacteriophage T12 is the prototype phage carrying the streptococcal erythrogenic toxin A (speA) gene. To examine more closely the phages involved in lysogenic conversion, we examined 300 group A streptococcal strains, and identified and isolated two new phages that carry the speA gene. The molecular sizes of these phage genomes were between 32 and 40 kb, similar to that of phage T12 (35 kb). However, as ascertained by restriction analysis, the physical maps of the new phage genomes were different from phage T12 and from each other. Hybridization analysis also showed that all of these phages were only partially related to one another and the speA gene was always located close to the phage attachment site. Additionally, colony hybridization showed that whereas phage T12 or one of its close relatives is the most common phage associated with the group A streptococci, phage 49 has a much stronger association with the speA gene. A defective phage was also found following pulsed field gel electrophoresis of total phage DNA. This phage appears to be a resident of strain T25(3)c and is found only following induction of a T25(3)c lysogen. Restriction enzyme analysis of the isolated defective phage DNA suggests that it is the source of the submolar amounts of DNA previously found in association with phage T12 digestion patterns. Additionally, the defective phage may serve as the site of integration of the speA gene-carrying phages described above. PMID- 1753943 TI - A multi-component upstream activation sequence of the Saccharomyces cerevisiae glyceraldehyde-3-phosphate dehydrogenase gene promoter. AB - The majority of the activation potential of the Saccharomyces cerevisiae TDH3 gene promoter is contained within nucleotides -676 to -381 (relative to the translation initiation codon). An upstream activation sequence (UAS) in this region has been characterized by in vitro and in vivo assays and demonstrated to be composed of two small, adjacent DNA sequence elements. The essential determinant of this upstream UAS is a general regulatory factor 1 (GRF1) binding site at nucleotides -513 to -501. A synthetic DNA element comprising this sequence, or an analogue in which two of the degenerate nucleotides of the GRF1 site consensus sequence were altered, activated 5' deleted TDH3 and CYC1 promoters. The second DNA element of the UAS is a 7 bp sequence which is conserved in the promoters of several yeast genes encoding glycolytic enzymes and occurs at positions -486 to -480 of the TDH3 promoter. This DNA sequence represents a novel promoter element: it contains no UAS activity itself, yet potentiates the activity of a GRF1 UAS. The potentiation of the GRF1 UAS by this element occurs when placed upstream from the TATA box of either the TDH3 or CYC1 promoters. The characteristics of this element (termed GPE for GRF1 site potentiator element) indicate that it represents a binding site for a different yeast protein which increases the promoter activation mediated by the GRF1 protein. Site-specific deletion and promoter reconstruction experiments suggest that the entire activation potential of the -676 to -381 region of the TDH3 gene promoter may be accounted for by a combination of the GRF1 site and the GPE. PMID- 1753944 TI - Genetic study and further biochemical characterization of a tobacco mutant that overproduces sterols. AB - A genetic and biochemical characterization is presented of a tobacco mutant that was previously shown to have an increased sterol content with an accumulation of biosynthetic intermediates. We first show that a precise regulation of the membrane sterol composition occurs in this mutant, via a selective esterification process. Indeed, sterols representing the usual end-products of the biosynthetic pathway are preferably integrated into the membranes as free sterols, whereas most of the intermediates pool is esterified and stored in cytoplasmic lipid droplets. It is further demonstrated that overproduction of sterols by the LAB1-4 mutant is due to a single nuclear and semi-dominant mutation. Finally, increase of biosynthesis and esterification of unusual sterols are shown to be responsible for the resistance of LAB1-4 calli to LAB170 250F, the triazole pesticide used to select this mutant. However, differentiated LAB1-4 tissues do not express the resistance trait, suggesting that sterol biosynthesis might not be the only site of action for the triazole at the plant level. PMID- 1753945 TI - Cloning and characterization of the Chlamydomonas moewusii mitochondrial genome. AB - We report that the mitochondrial genome of Chlamydomonas moewusii has a 22 kb circular map and thus contrasts with the mitochondrial genome of Chlamydomonas reinhardtii, which is linear and about 6 kb shorter. Overlapping restriction fragments spanning over 90% of the C. moewusii mitochondrial DNA (mtDNA) were identified in a clone bank constructed using a Sau3AI partial digest of a C. moewusii DNA fraction enriched for mtDNA by preparative CsCl density gradient centrifugation. Overlapping Sau3AI clones were identified by a chromosome walk initiated with a clone of C. moewusii mtDNA. The mtDNA map was completed by Southern blot analysis of the C. moewusii mtDNA fraction using isolated mtDNA clones. Regions that hybridized to C. reinhardtii or wheat mitochondrial gene probes for subunit I of cytochrome oxidase (cox1), apocytochrome b (cob), three subunits of NADH dehydrogenase (nad1, nad2 and nad5) and the small and the large ribosomal RNAs (rrnS and rrnL, respectively) were localized on the C. moewusii mtDNA map by Southern blot analysis. The results show that the order of genes in the mitochondrial genome of C. moewusii is completely rearranged relative to that of C. reinhardtii. PMID- 1753946 TI - Cloning, sequencing and characterization of the Saccharomyces cerevisiae URA7 gene encoding CTP synthetase. AB - The URA7 gene of Saccharomyces cerevisiae encodes CTP synthetase (EC 6.3.4.2) which catalyses the conversion of uridine 5'-triphosphate to cytidine 5' triphosphate, the last step of the pyrimidine biosynthetic pathway. We have cloned and sequenced the URA7 gene. The coding region is 1710 bp long and the deduced protein sequence shows a strong degree of homology with bacterial and human CTP synthetases. Gene disruption shows that URA7 is not an essential gene: the level of the intracellular CTP pool is roughly the same in the deleted and the wild-type strains, suggesting that an alternative pathway for CTP synthesis exists in yeast. This could involve either a divergent duplicated gene or a different route beginning with the amination of uridine mono- or diphosphate. PMID- 1753947 TI - DNA lesions that block DNA replication are responsible for the dnaA induction caused by DNA damage. AB - The initiation protein DnaA of Escherichia coli regulates its own expression autogenously by binding to a 9 bp consensus sequence, the dnaA box, between the promoters dnaAP1 and dnaAP2. In this study, we analysed dnaA regulation in relation to DNA damage and found dnaA expression to be inducible by DNA lesions that inhibit DNA replication. On the other hand, coding DNA lesions were not able to induce dnaA expression. These results suggest that an additional regulatory mechanism is involved in dnaA gene expression and that DnaA protein may play a role in cellular responses to DNA damage. Furthermore, they strongly suggest that in response to DNA replication inhibition by DNA damage, and enhanced (re)initiation capacity is induced by oriC. PMID- 1753948 TI - Effects of replacement of promoters and modification of the leader peptide region of the amy gene of Streptomyces griseus on synthesis and secretion of alpha amylase by Streptomyces lividans. AB - Five different mutations were introduced into the leader peptide region of the alpha-amylase gene of Streptomyces griseus IMRU 3570. A mutation which increased the positive charge of the N-terminal region of the leader peptide enhanced the secretion of alpha-amylase by two- to threefold. Replacement of the native promoter of the amylase gene by the promoter of the Tn5 neo gene or by the promoter of the saf gene resulted in a 16-fold increase in alpha-amylase secretion. The enhanced secretion of alpha-amylase obtained by using the most efficient promoters was due to a correlated increase in the amount of transcript formed. The translation and secretion processes in S. lividans are not a bottleneck for enzyme secretion even at very high transcription rates, since stimulation of transcription of the alpha-amylase gene results in a proportionate increase in secretion of the enzyme. PMID- 1753949 TI - Isolation and analysis of a cDNA clone that encodes an alfalfa (Medicago sativa) aspartate aminotransferase. AB - We have isolated an alfalfa leaf cDNA clone that encodes aspartate aminotransferase (AAT, EC 2.6.1.1) by direct complementation of an Escherichia coli aspartate auxotroph with a plasmid cDNA library. DNA sequence analysis of the recombinant plasmid, pMU1, revealed that a 1514 bp cDNA was inserted in the correct orientation and in-frame with the start of the lacZ coding sequence in the vector, pUC18. The resulting fusion protein is predicted to be 424 amino acids in length with a molecular weight of 46387 Daltons. The cDNA-encoded protein has a characteristic pyridoxal phosphate attachment site motif and has substantial amino acid sequence homology to both animal and bacterial AATs. Plasmid pMU1 encodes an AAT with a Km for aspartate of 3.3 mM, a Km for 2 oxoglutarate of 0.28 mM, and a pH optimum between 8.0 and 8.5. Several lines of evidence including Western blot analysis, the isoelectric point of the encoded protein, and the effect of pH on the activity of the fusion protein, suggest that the cDNA encodes the isozyme AAT-1 rather than AAT-2. Northern blot analysis showed that the aat-1 clone hybridized to a 1.6 kb transcript present in alfalfa leaves, roots and nodules. The relative concentrations of aat-1 mRNA in these tissues were 1:2:5, respectively. Thus, transcription of aat-1 appears to be induced during nodule development. Southern blot analysis suggested that AAT-1 in alfalfa is encoded by either a single-copy gene or a small, multigene family. PMID- 1753950 TI - [Selective cytotoxic effect of an immunotoxin on human erythroid tumor cells]. AB - The possibility of efficient directed elimination of human erythroblastoid cells by the conjugate of IgM-monoclonal antibody HAE9 directed against the erythroblast antigen and the A-chain of a plant toxin ricin has been demonstrated. The conjugate contained 2 molecules of A-chain per one antibody molecule. The efficiencies of the cytotoxic effect of native ricin and the conjugate were compared according to the number of binding sites on the surface of K562 cells as well as to the internalization rate of these molecules. As was shown, that the number of binding sites for the antibody approaches 2.7.10(4) molecules/cell, K a being equal to 1.7.10(8) M-1 while for ricin these indices constitute 2.4.10(5) and 4.6.10(8) M-1. Almost 100% of antibodies and 36% of ricin are internalized within 10 min at 37 degrees C. At a concentration 10(-11) of native ricin and 10(-10) of immunotoxin the 50% inhibition of growth of K562 cells carrying the erythroblast antigen on their surface is observed. PMID- 1753951 TI - [Cytotoxic properties of a recombinant hybrid of the A protein of Staphylococcus aureus with a fragment of exotoxin A of Pseudomonas aeruginosa]. AB - By gene-engineering technique a chimeric protein made up of fragments of Staphylococcus aureus protein A and . Pseudomonas aeruginosa exotoxin A has been constructed. The chimeric protein was shown to preserve features characteristic of its both constituents--it ADP-ribosylates elongation factor 2 and binds to Ig. Cytotoxic properties of the chimeric protein were studied in two model systems. Treatment of target cells in both systems was performed successively with antibodies against corresponding antigens and after washing--with recombinant chimeric toxin which bound to antibodies on the surface of target cells. In the first model system human B-lymphoma cells (Daudi line) carrying Ig molecules on their surface were treated with polyclonal antibodies against human Ig L-chains. In the other system, human T-lymphoma cells (Jurkat line) were treated successively with monoclonal antibodies against cell surface CD5 antigen and further on--with polyclonal antibodies against mouse Ig. In both systems, only a slight inhibition of the target cells' growth was registered. The probable reasons of low cytotoxic activity of the chimeric protein and prospects of increasing it are discussed. PMID- 1753952 TI - [Electron microscopic study of DNA compactization under the effect of putrescine]. AB - DNA-putrescine complexes were studied by electron-microscopy with the use of protein-free method. The latter gives the opportunity to investigate the interaction of DNA molecules spread on the surface layer of hypophase and the polyamine molecules in the thick layer of hypophase. Polyamine concentration varied from 5 x 10(-4) mM to 5 x 10(-1) mM. Under the low concentration of putrescine the complexes are represented by agglomerations of kinked knobbed fibres 10 to 20 nm thick, consisting of several fibres of duplex DNA. Upon increasing of putrescine concentration from 5 x 10(-4) to 1.5 x 10(-1) mM, the fibres become more thick (up to 25 nm), highly twisted and have the appearance of cylinders. Very often in the composition of complexes, it is possible to encounter the circular structures, which were formed at the expense of intermolecular interaction of different parts of the complex. The circular structures can serve as "embryos" of toroids of different sizes, that is of different degree of saturation with DNA and putrescine. At the concentration of putrescine 5 x 10(-1) mM the complexes have the appearance of toroids and structures on the basis of toroids, cylinders. The scheme of possible transitions of fibres of various thickness is proposed. The regularities of the compactization process, stimulated by polyamines, don't depend on the degree of compactization (the thickness of compacting fibre), that is they are similar for duplex DNA and for the fibres 25 nm thick, consisting of dozens of DNA molecules. PMID- 1753953 TI - [Conformation of the third domain of turkey ovomucoid in solution. Structural analysis by two-dimensional Overhauser nuclear effect spectroscopy]. AB - The conformations of a polypeptide chain of turkey ovomucoid third domain and its modified form with split reactive site peptide bond Leu-18--Glu-19 have been determined by the literary two-dimensional nuclear Overhauser effect spectroscopy data using an earlier suggested method. It has been found that the polypeptide domain backbone contains an alpha-helical fragment (residues 32-47), five segments having extended conformation (1-5, 11-17, 19-25, 29-31, 48-50) and beta turn type 1 (26-29). Segments 23-26, 28-31 and 50-51 form an antiparallel beta structure. Conformational states of the residues entering irregular domain segments have been analysed. Splitting of the reactive site peptide bond Leu-18- Glu-19 is shown to cause insignificant changes in the conformations of a number of amino acid residues except for Val-6 and Asp-7 ones which undergo essential conformational alterations. The conformations of domain in solution and of japanese quail ovomucoid third domain in crystal have been compared. The root mean-square deviations for phi and psi angles indicate their high similarity. The conformations of turkey ovomucoid third domain and proteinase inhibitor BUSI IIA in solution have been analysed. In spite of moderate (50%) homology of primary structures, some 75% of amino acid residues are shown to have close conformational phi and psi parameters. PMID- 1753954 TI - [Expression of human tissue plasminogen activator by recombinant cell lines from various animals]. AB - A number of recombinant cell lines which produce human tissue plasminogen activator (tPA) was obtained using different hosts--mouse, rat, hamster, simian and human cell lines. All types of recombinant lines secreted active r-tPA into conditioned medium. A slight difference between molecular weights of secreted variants of r-tPA was mediated by the different mechanisms of protein modification. Treatment of some recombinant cell lines with different substances resulted in increased levels of r-tPA production. PMID- 1753955 TI - [Use of the polymerase chain reaction for typing allelic variants of the human HLA-DQA1 by hybridization with oligonucleotide probes, specific for specific alleles]. AB - Class II HLA molecules are the most useful markers for susceptibility to different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). Polymerase chain reaction and hybridization with a set of allele-specific oligonucleotide have been used for analysis of allelic sequence variation. The analysis of frequencies of HLA-DQA1 alleles among 10 patients of the russian population revealed a uneven distribution. We have developed a method for preparing non-radioactive oligonucleotide probes with terminal deoxynucleotidyl transferase and Bio-11-dUTP. Comparison of biotinylated and 32P-labeled hybridization probes gave the same sensitivity for HLA-DQA1 typing of amplified DNA. Amplification of the HLA-DQA1 gene has been successful on 10 pg of total DNA. This amount of DNA is close to the amount of DNA in a single cell. Alternatively, HLA-DQA1 typing could be based on the analysis of buccal cells of saliva that would avoid the problem of individuals who object to giving blood samples. PMID- 1753956 TI - [Elimination of introns from the interleukin 1 beta genome by DNA amplification and expression of interleukin 1 beta in Escherichia coli]. AB - The use of the polymerase chain reaction was proposed for intron excision from genomic genes with known nucleotide sequences. Three exons (5, 6 and 7) of genomic interleukin 1 beta gene were amplified by means of thermostable DNA polymerase TthI from Thermus thermophilus on the base of cloned in M13 phage human genomic interleukin 1 beta gene. Synthetic oligonucleotides complementary to sequences flanking exons were used as primers. The fragments obtained by exon DNA amplification were joined in the correct order due to reciprocal complementation of end sequences, that was foreseen during synthesis of oligonucleotide primers followed by amplification of the enlarged fragments. As a result the structural interleukin-1 beta gene consisting of three exons was assembled. DNA sequences carrying the ATG initiation codon and XbaI recognition site at the 5'-end, and PstI recognition site at the 3'-end (essential for insertion into the expression vector) were formed by the additional end sequences of primers. The nucleotide sequence analysis of the obtained structural gene revealed its complete identity with natural interleukin 1 beta human gene. We created the expression vector pPR114 with phage lambda promoter PR thermo inducible in case of the cIts857 repressor presence in cells. It was used for expression of the present gene. The interleukin 1 beta synthesized in E. coli had biological activity. PMID- 1753957 TI - [Cloning of Chrysanthium stund virion cDNA in pUC19 plasmid and the use of cloned cDNA for detecting the virion]. AB - 26 base long deoxyribonucleotide complementary to the lower part of the Central Conserved Region of chrysanthemum stund viroid (CSV) was used for synthesis of the first strand cDNA. The cDNA was cloned into plasmid vector pUC19 and the primary structure was determined. Cloned, full length cDNA was used as hybridisation probe for detection of CSV. It was possible to detect about 26 pg of purified CSV RNA immobilized on nitrocellulose filters using 32P-labeled probe. In the case of biotinylated probe it was possible to detect about 26 pg of purified CSV RNA visualizing results by streptavidin-alkaline phosphatase conjugates. It has been shown that such a cloned cDNA can be used for wide scale detection of CSV. PMID- 1753958 TI - [Nucleic acid synthesis and spatial organization of DNA in the presence of heparin and the quaternary ammonium salt of the conidin oligomer-25]. AB - A comparative study of polyconidin effects in the replicative and transcription activity of hepatocyte DNA in intact animals, and on peculiarities of spatial organization DNA in the DNA complex with oligomer-25 conidin was carried out. It was shown that polyconidin binding to DNA results in "cross-linking". This process is accompanied by formation of liquid-crystalline dispersion without abnormal optical activity. Liquid crystals possess high density packing of DNA molecules complexed with quaternary ammonium salt of oligomer-25 conidin. The addition of heparin to liquid-crystalline dispersions or phases, destroys the structure of the DNA complex with quaternary ammonium salt of oligomer-25 conidin. As a result "free" DNA molecules appear, they form the cholesteric liquid-crystalline phase. An increase in transcription activity and synchronization of DNA synthesis in hepatocyte was demonstrated. A correlation between chromatin modification and biological activity of chromatin after formation of the DNA--oligomer-25 conidin complex is proposed. PMID- 1753959 TI - [Suppression of translation in vitro of the mRNA of the M1 protein of influenza virus using antisense oligonucleotides]. AB - Effect of antisense oligonucleotides on the in vitro translation of the influenza virus M1 protein mRNA was investigated. The most efficient arrest of mRNA translation was achieved by simultaneous action of two or three oligonucleotides (14-16-mers) complementary to the juxtaposed sequences in the 5'-terminus of the molecule around and upstream of the initiation codon. PMID- 1753960 TI - [Electron microscopic study of compactization of individual DNA molecules in films during the interaction with histone H1]. AB - The protein-free method was applied for the investigation of histone H1 DNA complexes formation. The main advantage of this method is the possibility to get intramolecular compact structures at interaction of individual spread molecules of DNA with histone H1. It was shown that in the presence of 0.2-5 micrograms/ml of histone H1 in hypophase there are three types of structures on electronmicroscopic preparations: fibres of non-compacted DNA, compact fibres with twisted strands of duplex DNA and compacted rod-like and circular structures where separate fibres of duplex DNA could not be distinguished. The study of compact structures morphology allows to conclude that they are formed by side-by side association of DNA fibres, as it takes place in the case of triple rings formation at the compactization of circular DNA due to trivaline binding. At increasing ionic strength there is a tendency for transition from second type structures to the third type structures. The latter can be explained by transition from non-cooperative to cooperative binding of histone H1 to DNA. PMID- 1753961 TI - [Conserved and variable segments of the snake phospholipase A2 amino acid domain]. AB - Homologous amino acid sequences of phospholipases A2 of snakes belonging to families Elapidae, Viperidae and Colubridae were considered in order to study the location of conservative and variable regions. To identify significant conservative and variable regions a comparison between two groups of aligned sequences of snake phospholipases A2 was successfully applied. The phospholipases A2 sequences were divided into two groups (taxons) according to the phylogenetic tree reconstructed from the pair distance matrix. Results of the comparison were plotted to facilitate the identification of significant conservative and variable regions. It was shown, that the results of the comparison between two phylogenetic groups of snake phospholipases A2 didn't depend much on the number of each group representatives, and the location of conservative and variable regions didn't significantly change if one of the groups was represented by the single sequence. It should be mentioned, that the more the phylogenetic difference between groups of phospholipases A2 the more was the number of significant conservative and variable regions. The knowledge of the number and location of conservative and variable regions and their dependence on phylogenetic relations between the compared taxons can be used to predict the synthetic peptide structure to obtain antibodies of various specificity. These antibodies may have either a wide range of cross-reactivity against all of phospholipases A2 or a limited range of cross-reactivity against phospholipases A2 of one taxon. PMID- 1753962 TI - [A method of equalizing the level of DNA sequences of varying amount in a heterogeneous DNA mixture]. AB - A method for the equalization of double-stranded DNA concentrations in the mixture which may be used for equalizing double-stranded cDNA concentrations involves thermal denaturation of the double-stranded DNA mixture followed by reassociation. The initial reassociation rate is Vi = Ki.(single-stranded DNA)2, and by the end of the process the concentrations of the unreassociated molecules for different DNAs should be approximately equal. Using hydroxylapatite chromatography one can separate single-stranded DNAs from double-stranded DNAs and carry out complete single-stranded DNAs reassociation. The new ratio of different double-stranded DNA concentrations would be almost 1. PMID- 1753963 TI - [Heterogeneity and avidity of autoantibodies reacting with DNA]. AB - Subpopulations of auto-antibodies to DNA were isolated by affinity procedures from sera of two patients with SLE and from IgG of healthy donors after ion exchange chromatography ("hidden" auto-antibodies). It was found that two subpopulations of auto-antibodies are present in SLE sera just as fractions of "hidden" auto-antibodies consist of three subpopulations. The dissociation constants were measured by ELISA for the interaction of all subpopulations of auto-antibodies to DNA. It is shown that KD are very high and identical no matter of whether they were prepared from SLE sera of from IgG of healthy donors. The analogy of two types of auto-antibodies (SLE auto-antibodies and "hidden" auto antibodies) is discussed in this paper. PMID- 1753964 TI - [Structure of nucleosomes. Localization of the H2A and H2B histone segments interacting with DNA using DNA-protein crosslinking]. AB - Histones' H2A and H2B peptidic points which interact with nucleosomal DNA have been identified by using the methods of DNA--protein covalent cross-linking. H2B can be linked to DNA via its N-terminal tail and via several lysines contained within residues 24-34. The most prominent site of histone H2A covalent linking to DNA is His-123, the less prominent being Lys-119 and Lys-124. PMID- 1753965 TI - [Conformational transitions of human serum albumin depending on pH. Study using tritium markers]. AB - Accessible surfaces of the HSA molecule in N-, F- and B-forms were studied in the present work by tritium labelling method which allowed to obtain detailed information on N-F- and N-B-transitions. In was shown that the F-form in comparison top the N-form is characterized by more high accessibility of Ser, Ala, Ile, Tyr, Phe, His, Arg, Pro, Val and Phe residues and in the B-form Tyr, Ser, Arg, Gly, Ile, Phe and Pro residues turn to be highly accessible. Full accessible surfaces of protein molecule at N-F- and N-B-transitions increase respectively from 39,000 to 70,400 A2 and from 39,000 to 47,000 A2. Basing on the prevailing increase of hydrophobic residues accessibility it is supposed that the molecule expansion testifies the separation of the subunits forming the molecule. PMID- 1753966 TI - [Amplification using one-sided polymerase chain reaction, cloning and determination of primary structure of 5'-untranslated cDNA segments coding the somatogenic growth hormone receptor from rat liver]. AB - The method of ligation-mediated, single-sided polymerase chain reaction was applied for the amplification of 5'-untranslated regions of cDNA coding for somatogenic growth hormone receptor from rat liver. The products of polymerase chain reaction were cloned and sequenced. Two variants of 5'-untranslated sequences of growth hormone receptor cDNA corresponding to products of alternative splicing of pre-mRNA were found. PMID- 1753967 TI - [Restriction analysis of autonomously replicating molecules containing exogenous DNA in a transgenic silkworm line]. AB - Early embryos of the silkworm, Bombyx mori, were injected with plasmid p1,5LTR, harboring DNA copies of the Rous sarcoma long terminal repeats (LTR). Three generations of insects were obtained whose total DNA carried DNA sequences of the injected plasmid. Plasmid rescue method revealed that exogenous DNA was present in extrachromosomal molecules that harbored also cellular DNA sequences. A restriction map of the plasmid rescued from the F2 generator was constructed. PMID- 1753968 TI - Staking out the law. PMID- 1753969 TI - AIDS and surrogate decision making. PMID- 1753970 TI - Surrogate decisions in New York State on sustaining life. PMID- 1753971 TI - The physician's experience: infants and children. PMID- 1753972 TI - The physician's experience: patients in intensive care. PMID- 1753973 TI - The physician's experience: elderly patients. PMID- 1753974 TI - Surrogate decision making for incompetent adults: an ethical framework. PMID- 1753975 TI - Foster parents as surrogates for infants and young children. PMID- 1753976 TI - History of drug use and drug control. PMID- 1753977 TI - The epidemiology of cocaine use in New York State. PMID- 1753978 TI - Paternalism and drug abuse. PMID- 1753979 TI - Pharmacology of the drugs of abuse and the development of public policy. AB - It is fascinating that the morality, ethics, and effectiveness of current drug prohibition policies are being criticized in an era when drug use is declining in most segments of society. The current era is also marked by increasingly restrictive policies against drug use and users, including much enhanced interdiction efforts, calls for tougher penalties and more jails, and extensive drug screening programs at the work site. Summary dismissal of workers or students who use drugs is increasingly advocated. Two distinct and opposing currents advocating policy change have emerged, one for legalization, the other for greater restriction. The current inner-city rise in drug use, particularly of cocaine and "crack," and the remarkable increase in drug-related crime is probably providing the impetus for both lines of thinking. Yet both views appear extreme and neither seems to offer a promising social policy. It is critical that we continue to attempt to develop effective strategies for reducing the impact of drug taking on the individual and society. Whereas I am sensitive to the ethical and legal perspectives of the proponents of legalization, pharmacologic and social issues persuade me that legalization of heroin and cocaine would lead to a marked increase in drug dependence and an increase in drug-related disability and crime. In response to the idea that the legalization and taxation of drug use would provide resources for more effective research, prevention, and treatment, my sense is that we should not wait for legalization but should embark on that long and expensive course immediately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1753980 TI - Drug policy in New York City. PMID- 1753981 TI - Drug use and public policy. PMID- 1753982 TI - Drugs and the social body. PMID- 1753983 TI - The physician as a servant of public policy. PMID- 1753984 TI - Doctors' dilemmas: bioethical challenges. PMID- 1753985 TI - The personal ethics of the physician: curing medicine from within. PMID- 1753986 TI - Medical ethics: a broader definition. PMID- 1753987 TI - HIV infection in drug abusers: research implications of descriptive studies. PMID- 1753988 TI - Potential cofactors in the outcomes of HIV infection in intravenous drug users. PMID- 1753989 TI - How can results of longitudinal studies help mathematicians model the HIV epidemic among intravenous drug abusers and the general population? PMID- 1753990 TI - Natural history of HIV infection in gay men and intravenous drug users. PMID- 1753991 TI - Sampling issues for natural history studies including intravenous drug abusers. PMID- 1753992 TI - Toward comprehensive studies of HIV in intravenous drug users: issues in treatment-based and street-based samples. PMID- 1753994 TI - Emerging technologies and new directions in drug abuse research. An overview. PMID- 1753993 TI - Strategies for enhancing existing studies of the natural history of HIV-1 infection among drug users. PMID- 1753995 TI - Combined use of solid-state nuclear magnetic resonance spectroscopy, small-angle x-ray diffraction, and differential scanning calorimetry in studies of cannabinoid: membrane interactions. PMID- 1753996 TI - Characterization and localization of cannabinoid receptors in brain: an in vitro technique using slide-mounted tissue sections. PMID- 1753997 TI - New developments in radiotracers for positron emission tomography. PMID- 1753998 TI - Use of positron emission tomography to study cocaine in the human brain. AB - It is feasible to directly image and measure the concentration of different drugs of abuse and their consequences on regional brain function and neurotransmitter activity with PET. Although PET is a relatively new technique, it already is proving to be useful in disclosing the mechanisms of toxicity reinforcement and addition of drugs of abuse. PMID- 1753999 TI - A mechanistic basis for design of selective agonists for 5-HT receptors. PMID- 1754000 TI - Peptidomimetic opioids--synthesis, spectroscopy, and computer simulations. PMID- 1754001 TI - Modified solid-phase methods for the rapid synthesis of opioid peptides. PMID- 1754002 TI - Important compounds in the cocaine class: a synthesis overview. PMID- 1754003 TI - FDA regulatory requirements for investigational new drugs and new drug applications: an update. PMID- 1754004 TI - 3D-searching: an overview of a new technique for computer-assisted molecular design. PMID- 1754005 TI - Voronoi binding site models. PMID- 1754006 TI - Protein structure determination in solution using nuclear magnetic resonance spectroscopy. PMID- 1754008 TI - Methodological issues in controlled studies on effects of prenatal exposure to drug abuse. PMID- 1754007 TI - Drug exposure to the fetus--the effect of smoking. PMID- 1754009 TI - Neurobehavioral organization of the newborn: opportunity for assessment and intervention. AB - A functional model has been formulated that attempts to specify the behavioral subsystems of functioning that exemplify in their respective interplay an infant's individuality of behavioral functioning in the manner in which they move from stable to disorganized functioning and in the flexibility with which they maintain organized functioning in the face of varied exogenous and endogenous events. Based on this model, Als and colleagues have attempted to develop systematic assessments, the APIB and the K-Box Paradigm, to quantify the degree of differentiation and modulation of these behaviorally defined subsystems of functioning. It is hypothesized that the differences documented via these assessments are brain based (i.e., part of the child's biological makeup, which is influenced by the intrauterine and extrauterine environment, be it sensory and/or drug exposure, and which shows a recognizable pattern along a definable trajectory). PMID- 1754010 TI - Substance abuse in pregnancy: effects on cardiorespiratory function in the infant. PMID- 1754011 TI - The effect of cocaine on developing human brain. PMID- 1754012 TI - Measurement of drug-induced physical and behavioral delays and abnormalities in animal studies: a general framework. PMID- 1754013 TI - Pharmacokinetic correlates of fetal drug exposure. PMID- 1754014 TI - Postnatal development of cardiac and respiratory control following prenatal drug exposure. AB - Of primary importance in the consideration of animal models of prenatal drug exposure is the recognition of interdependence among physiologic systems, the pervading influence of sleep and waking states, and the potential interaction between drug-induced structural changes and physiologic function. It is difficult for a drug effect on the cardiovascular system not to modify respiratory pattern; any change in blood pressure, systemic perfusion, or heart rate is immediately reflected in breathing; respiratory pattern, in turn, through negative thoracic pressure and other sensory activity, can alter cardiac patterning. The respiratory system itself is one component of a somatic motor system, and neural motor control structures undergo substantial modification by drug action. Enhancing or diminishing any aspect of interaction is the influence of sleep states, which nonlinearly can alter relationships between physiologic systems, occasionally dissociating systems, as in the case of temperature effects on breathing during REM sleep. Finally, drug-induced structural changes that alter morphology of the upper airway can result in obstructive respiratory events, leading to pronounced cardiovascular sequelae. PMID- 1754015 TI - Endocrine function as a target of perinatal drug effects: methodologic issues. AB - The goal of this chapter is to indicate potential endocrine targets of perinatal drug exposure, to describe the methodologic issues involved in detecting changes in hormone secretion, and to provide examples of several endocrine systems in which exposure to drugs during development significantly impaired normal endocrine development. Finally, we attempted to show that endocrine function is both a target and useful marker for detecting effects of drug of abuse on development that provides the advantages of accurate quantitation and relative response stability across ontogeny. PMID- 1754016 TI - Assessment of teratogenic effects on cognitive and behavioral development in infancy and childhood. PMID- 1754017 TI - New methodologies for evaluating residual brain damage in infants exposed to drugs of abuse: objective methods for describing movements, facial expressions, and communicative behaviors. PMID- 1754018 TI - Rationale and methodologies for developing nonhuman primate models of prenatal drug exposure. PMID- 1754019 TI - Following drug-exposed infants into middle childhood: challenges to researchers. PMID- 1754020 TI - Patterns of growth and development in narcotic-exposed children. AB - The results of the studies reviewed indicate that intrauterine growth is adversely affected by drug use during pregnancy. Whether the impairment is a direct effect of narcotic exposure or is the result of the interaction of deleterious health, environmental, and socioeconomic factors closely associated with the lifestyle of the woman who abuses drugs cannot be determined at present. Reports on the long-term effects of drug use on growth and intellectual functioning in the offspring of women who abuse drugs are not consistent. While some studies indicate that most of the exposed infants exhibit catchup growth by 6 months of age (Lifschitz et al. 1983, 1985), one methodologically strong study suggests that methadone may have a small direct teratogenic effect reflected in reduced head size at 2 years of age (Hans 1989). Unexplained is the pattern of growth deceleration observed in some narcotic-exposed children (Lifschitz et al. 1983, 1985). The few available reports on long-term outcome concur that narcotic exposed children have a high incidence of behavioral and learning problems (Strauss et al. 1979; Rosen and Johnson 1985; Wilson 1989), but population studies have been too small to demonstrate that they differ significantly from controls. There is a suggestion that narcotic use during pregnancy promotes a biological vulnerability to adverse environments, manifested in the neurobehavioral and intellectual areas. PMID- 1754021 TI - Integrity of psychopathology diagnoses across the lifespan. PMID- 1754022 TI - Selected methodologic issues in investigations of prenatal effects of cocaine: lessons from the past. PMID- 1754023 TI - Methodological issues in studying cocaine use in pregnancy: a problem of definitions. PMID- 1754024 TI - Use of birth defects monitoring programs for assessing the effects of maternal substance abuse on pregnancy outcomes. AB - We have attempted to demonstrate that birth defects surveillance systems are a unique adjunct to clinical research data on maternal exposures, including substances of abuse. Surveillance system data reflect the experiences of the populations from which they are drawn and the characteristics of the people in those populations. Sensitive systems may reveal trends in health status and changes in behavioral, cultural, social, or environmental exposures. They can be used to monitor changing trends, to identify clusters for investigation, to generate and test hypotheses, and to conduct epidemiological studies. For researchers to interpret data derived from surveillance systems appropriately and wisely, they need a thorough knowledge of the data sources, the data-collection procedures, and the intent of the surveillance systems. Researchers using surveillance data should have a thorough understanding of the quality of their data and the methodologic subtleties that bear on its interpretation; researchers reviewing scientific literature based on surveillance data should be aware of the strengths and limitations inherent in the data. PMID- 1754025 TI - What we can learn from the status of the newborn. PMID- 1754026 TI - In situ differentiation between nevi and malignant melanomas by fluorescence measurements. PMID- 1754027 TI - German Society for Pharmacology and Toxicology. Abstracts of the third winter meeting. 4-6 December 1991, Hannover. PMID- 1754028 TI - Protein inhibitors of proteinases from brain. PMID- 1754029 TI - Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain. AB - The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3 methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guinea-pig brain. Guinea pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxone-precipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined. PMID- 1754030 TI - Immunocytochemical localization of leucomyosuppressin-like peptides in the CNS of the cockroach, Leucophaea maderae. AB - Immunocytochemistry was used to determine sites of synthesis and pathways for the transport of the neuropeptide, Leucomyosuppressin (pQDVDHVFLRFamide) in the cockroach, Leucophaea maderae. This study led to identification of neurons in the brain and thoracic ganglia reactive to polyclonal antibodies raised against this peptide. No immunoreactive cells were found in the subesophageal or abdominal ganglia. Although the corpus cardiacum contained no intrinsic cells immunoreactive to LMS antibodies, the periphery of this organ and that of the nervi corporis allati contain an abundance of LMS-reactive terminals. PMID- 1754031 TI - In vivo metabolism of fluorescent ceramide in central nervous system myelin of adult rats. AB - The metabolism of sphingolipids in the central nervous system (CNS) has been studied in adult rats by intraventricular administration of fluorescent ceramide (CER). Rats were sacrificed at various time points post inoculation and the fluorescence of CER, cerebrosides (CB), sulfatides (SULF) and sphingomyelin (SPM) was determined in the CNS myelin and in the pellet, containing mainly microsomes, obtained by Norton myelin preparation. The incorporation of fluorescence was more in the pellet than in the myelin at all times studied. Initially the fluorescence present in the pellet was prevalently due to untransformed CER but an increase of fluorescent products with time was observed. CB was the main product up to 2 h post inoculation, then it decreased with concomitant increase of fluorescent SULF. In the myelin we did not observe differences in incorporation and transformation of fluorescent CER with time: CB was the main fluorescent product at all times studied. At 0.5 h post inoculation the fluorescence, observed by fluorescence microscope, was located in the cell lining the ventricles while after 24 h it appeared also in the paraventricular areas. PMID- 1754032 TI - Cerebral ischemia: changes in brain choline, acetylcholine, and other monoamines as related to energy metabolism. AB - The relationship of cerebral neurotransmitters acetylcholine (ACh), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT) to the energy state of the brain was examined in mice at various times following complete ischemia produced by decapitation, in gerbils submitted to transient global ischemia (10 min bilateral carotid artery occlusion, 5 or 30 min recirculation), and in rats 24 hr after irreversible microembolism. Ischemia caused significant reductions in brain monoamine concentrations. The alterations in NA, DA, and 5HT levels persisted during recirculation and were unrelated to energy restoration. They were accompanied by an increase in the concentrations of related metabolites, suggesting that synthesis was unable to compensate for the release of the transmitters at early post-ischemic time periods. As described for the catecholamines and 5HT, ischemia resulted in a significant decrease in ACh level, but recirculation was associated with a rapid increase in ACh concentration. Impaired synthesis and/or increased release of ACh can be responsible for the decrease in ACh concentration during ischemia. Early post-ischemic elevation of ACh may be related to the large increase in brain choline brought about by ischemia. PMID- 1754033 TI - Size and charge isomers of acetylcholinesterase in the cerebral cortex of young and aged rats. AB - Previous studies in this laboratory showed an age-related decline of acetylcholinesterase (AChE) activity in the cerebral cortex of rats. In the present study the age-related differences in enzymatic activity were evaluated in terms of individual molecular forms. Extracts containing total, soluble and membrane-bound AChE were analyzed both by ultracentrifugation in sucrose gradient and by non-denaturing gradient polyacrylamide gel electrophoresis. By ultracentrifugation two molecular forms, namely 10S and 4S (corresponding to tetrameric-G4 and monomeric-G1 forms, respectively) were separated in extracts of total and soluble AChE, while only 10S forms were present in extracts of membrane bound AChE. Electrophoresis of soluble AChE extracts revealed slowly- and fast migrating bands, grouped in two clusters of at least three bands each; membrane bound AChE contained only a single slowly-migrating band. Electrophoresis of the single forms isolated by ultracentrifugation showed that slowly- and fast migrating bands corresponded to G4 and G1 forms, respectively. Therefore, in soluble AChE no one-to-one relationship between charge- and size-isomers was observed; on the contrary, such relationship has been shown for membrane-bound AChE. This implies that soluble G4 forms and membrane-bound-G4 forms are electrophoretically different, being heterogeneous the former and homogeneous the latter. The age-related decline of total AChE, accompanied by a decrease of G4/G1 ratio, depended mainly on a decrease of membrane-bound AChE while soluble AChE and its G4/G1 ratio was unchanged. The qualitative pattern of charge isomers was not modified by aging. PMID- 1754034 TI - The effect of medial forebrain bundle lesion on thyrotropin secretion in the rat. AB - The medial forebrain bundle (MFB) was partially lesioned with 6-hydroxydopamine (6-OHDA) in order to investigate the effect of deficient central noradrenergic regulation on thyrotropin (TSH) secretion in the rat. 6-OHDA injection into the MFB significantly reduced the noradrenaline (NA), dopamine (DA) and serotonin (5 HT) content of the whole hypothalamus. NA and 5-HT concentrations were also significantly decreased in the paraventricular nucleus (PVN). The MFB lesion did not affect the clonidine (250 micrograms/kg, i.p.) induced stimulation of TSH release or the isoproterenol (1 mg/kg i.p.) induced decrease in TSH levels. Thyrotropin releasing hormone (TRH, 5 micrograms/kg i.v.) caused a similar significant stimulation of TSH secretion in lesioned and non-lesioned rats. The present results do not support the hypothesis that the blunted TSH response to TRH observed in depressed patients results from a deficiency in noradrenergic neurotransmission. PMID- 1754035 TI - Receptor-mediated supra-additive activation of guinea pig superior cervical ganglion adenylate cyclase: role of Mn2+ ions and calmodulin. AB - The effects of Mn2+ and calmodulin were studied on the basal and agonist modulated adenylate cyclase activity of the guinea pig superior cervical ganglion. The divalent cation strongly stimulates the basal and agonist-modulated enzyme in a concentration-dependent manner. Moreover, in the presence of Mn2+ the inhibitory effects of "high" GTP concentrations and of D-Ala2-Met-enkephalinamide on adenylate cyclase are eliminated, while the stimulation exerted by prostaglandin E2 and the supra-additive activation of the enzyme by the combination of the two drugs are unaffected. In EGTA-washed, calmodulin-depleted membrane preparations, Mn2+ still activates the cyclase but the enkephalin inhibition and the superactivation of the enzyme induced by the combination of opiate and prostaglandin are lost, both in the absence and in the presence of the cation. Reconstituting the depleted membranes with exogenous Ca2+/calmodulin fully restored the enzyme responsivity to the combination and, partially, to the enkephalin. The findings suggest the existence in the guinea pig superior cervical ganglion of both the calmodulin-sensitive and differently regulated calmodulin-insensitive adenylate cyclase. PMID- 1754036 TI - Dependence of the electrical activity of the hippocampus on the probability of reinforcement of an alimentary conditional stimulus. AB - The dynamics of the changes in the number of instrumental motor reactions and in the frequency of cardiac contractions and of the theta rhythm of the hippocampus during the replacement of constant reinforcement by various schedules of probabilistic reinforcement of an alimentary conditional stimulus were investigated in three dogs. At the 70 and 50% level of reinforcement, the instrumental reflex appeared in response to all of the presentations of the signal stimulus. The greatest decrease in the number of respondent reactions was observed at 5% probability. The pulse rate both in the intersignal period and during the receipt of an empty feeder depended on the probability of reinforcement employed and on the individual characteristics of the animals. The frequency of the theta rhythm in all of the dogs was highest at the 30% level; the lowest values were observed at the 5% level of reinforcement. The data obtained again attest to the complex genesis of emotional excitation, the magnitude of which depends both on the informational (indeterminacy) and on the motivational (the significance of the reinforcement) factors. PMID- 1754037 TI - Neurobiology of the integrative activity of the brain. Dynamics of the activational and inhibitory types of synchronization of cortical neurons during the realization of a defensive reflex and of internal inhibition. AB - An increase in synchronization of the activational type (coincidence of the presence of impulse activity), and a decrease of the inhibitory type (coincidence of both the presence and absence of impulse activity), in the operation of close lying neurons were observed in the visual and sensorimotor areas of the new cortex and in the hippocampus of wakeful non-immobilized rabbits in response to the combination of flashes of light with electrodermal stimulation (EDS) of the extremity. An increase in the synchronization of the neurons of the inhibitory type took place in the visual cortex in response to flashes against the background of the conditional inhibitor, i.e., continuous light, and changes in synchronization, similar to the effect of pain reinforcement but significantly weaker, appeared in the sensorimotor cortex and in the hippocampus. An increase in synchronicity of the activational type took place primarily in pairs of neurons with increase in the same direction in the frequency of impulse activity in response to a stimulus, and of the inhibitory type, took place with its decrease. In addition, both kinds of changes in synchronization appeared in a significant portion of the pairs of neurons with changes in the frequency of impulse activity of different directions. PMID- 1754039 TI - Change in behavior with the development of long-term sensitization of a defensive reflex in the edible snail. PMID- 1754038 TI - Influence of nembutal on the impulse activity of cells of embryonal nervous tissue transplanted into the rat brain. AB - The average frequency of the impulse activity of neurons of an allograft of embryonal cortex, in the brain of adult Wistar rats, under nembutal anesthesia was four times lower than in nonanesthetized animals; at the same time the variability of the activity of the cells of the graft, with respect to the frequency and pattern of impulse activity, decreased. As compared with the unanesthetized animals, half as many cells of the graft reacted to tactile stimulation of the contralateral hind extremity; the neuronal reactions to the stimulation of somatic receptors of the ipsilateral side of the body completely disappeared. PMID- 1754040 TI - A new pathway of the central nervous regulation of carbohydrate homeostasis. PMID- 1754041 TI - Metabolism of the sex steroids in the hypothalamus and its role in the neuroendocrine regulation of reproduction. PMID- 1754042 TI - Morphochemical features of the brain of rats genetically predisposed to catalepsy. PMID- 1754043 TI - Phenomena of motility in the sensory neuron of a spinal cord ganglion with stimulation of its peripheral receptors. PMID- 1754044 TI - Posttetanic and frequency potentiation in slices of rat olfactory cortex. AB - The electrical tetanization of the lateral olfactory tract at a frequency of 30/sec for 15 sec elicited the development of posttetanic potentiation of populational EPSP and IPSP in surviving slices of rat olfactory cortex. The stimulation of the lateral olfactory tract by series of stimuli at a constant frequency of 10/sec and with intervals of 4-5 sec between series facilitates the emergence of the phenomenon of frequency potentiation. The data obtained indicate that such forms of functional plasticity as posttetanic and frequency potentiation are manifested in the pyriform cortex. PMID- 1754045 TI - Intracentral interstructural relationships in the process of kindling electrostimulations of the hippocampus. AB - The features of the development of hippocampal kindling as a function of intracentral interstructural relationships formed during electrostimulations has been studied in 13 rabbits by means of electrodes chronically implanted in the brain (cerebral cortex, hippocampi, amygdalar nuclei, rostral portions of the caudate nuclei). The interstructural relationships were evaluated on the basis of the expressivity of the epileptic activity in various structures of the brain and on the basis of its dependence on the activity in the primary pathological focus. It was shown that in the case of the formation in the primary hippocampal epileptic focus of the pathological determinant (as described by G.N. Kryzhanovskii), which determine the activity of other structures, the kindling syndrome develops rapidly. If, on the other hand, competitive suppressive influences predominate in the interrelationships between the primary and secondary epileptic foci, which was most strikingly manifested between the hippocampal epileptic foci, then the pathological determinant does not form in this region and the kindling syndrome does not develop. PMID- 1754046 TI - Effects of the electrostimulation of various areas of the dorsal motor nucleus of the vagus on the electrical activity of the stomach wall. AB - The effects of the stimulation of various segments of the dorsal motor nucleus of the vagus on the electrical activity of the wall of the pyloric region of the stomach were studied with the use of microelectrode techniques in acute experiments in cats. It was established that the maximal changes of the parameters of the electromyogram are recorded during the stimulation of the zone of the nucleus 0(-) +1.5 mm rostral to the obex. PMID- 1754047 TI - Role of the rapid neurogenic component and its constituents in the organization of effort hyperpnea. AB - An investigation of the role of the rapid neurogenic component and its constituents in the organization of effort hyperpnea was carried out in athletes during physical loads increasing stepwise. The contribution of the condition reflex constituent in the general ventilatory response increases after the subject became acquainted with the increase in the severity of the demands, while with the use of loads in randomized order, its magnitude was approximately identical. With an increase in the metabolic cost of the work, the contribution of the rapid neurogenic component to the overall magnitude of the effort hyperpnea progressively decreases. The tendency to increase in the rapid neurogenic component in experienced athletes is the consequence of adaptive change due to the condition reflex constituent. PMID- 1754048 TI - Errors in the differential diagnosis of various types of nonepileptic paroxysms in the initial period of their occurrence. PMID- 1754049 TI - Changes in cerebral blood flow and their correction in the interparoxysmal period of epilepsy. PMID- 1754050 TI - Of dreaming and wakefulness. AB - Following a set of studies concerning the intrinsic electrophysiology of mammalian central neurons in relation to global brain function, we reach the following conclusions: (i) the main difference between wakefulness and paradoxical sleep lies in the weight given to sensory afferents in cognitive images; (ii) otherwise, wakefulness and paradoxical sleep are fundamentally equivalent brain states probably subserved by an intrinsic thalamo-cortical loop. From this assumption, we conclude that wakefulness is an intrinsic functional realm, modulated by sensory parameters. In support of this hypothesis, we review morphological studies of the thalamocortical system, which indicate that only a minor part of its connectivity is devoted to the transfer of direct sensory input. Rather, most of the connectivity is geared to the generation of internal functional modes, which may, in principle, operate in the presence or absence of sensory activation. These considerations lead us to challenge the traditional Jamesian view of brain function according to which consciousness is generated as an exclusive by-product of sensory input. Instead, we argue that consciousness is fundamentally a closed-loop property, in which the ability of cells to be intrinsically active plays a central role. We further discuss the importance of spatial and temporal mapping in the elaboration of cognitive and perceptual constructs. PMID- 1754051 TI - The organization of serotonergic projections to cerebral cortex in primates: regional distribution of axon terminals. AB - Serotonergic axons are widely distributed in the primate forebrain and represent the most abundant ascending projection from the reticular formation. Immunocytochemical methods have been utilized to examine the density, laminar distribution and morphology of serotonergic axons in both primary projection (motor, somatosensory) and association areas (dorsolateral prefrontal, area 5) as well as in the hippocampus and in cingulate cortex of rhesus and cynomolgus macaques. Serotonergic axons are present in all areas of cortex examined, and all cortical layers receive serotonergic afferents. However, the intracortical distribution of serotonergic axon terminals is not uniform; rather, different regions of cortex exhibit dissimilarities in both the density and laminar distribution of serotonergic axons. Thus, there are local patterns of serotonin innervation that are characteristic of each cortical area. Highly diverse patterns of serotonin innervation are found in heterotypical areas of cortex; more subtle variations are present among homotypical areas. Two morphologic types of serotonergic axon terminals, fine and beaded, are present in all cortical areas, and they typically exhibit different laminar distributions: in most areas of neocortex, beaded axons predominate in layer I while fine axons predominate in layers II-VI. However, exceptions to this pattern were observed in primary visual cortex and in the hippocampal formation. The distinctive local patterns of serotonin innervation observed in this study indicate that raphe-cortical projections are likely to have differential influences on particular cytoarchitectonic areas of cerebral cortex in the primate. Moreover, the discrete laminar distribution of serotonin axons suggests that serotonergic projections selectively innervate particular neuronal elements in cerebral cortex. The present findings suggest that the two classes of serotonergic axons, fine and beaded, which have different patterns of termination, affect different sets of cortical neurons. In addition, these two serotonergic projections may be associated with different sets of serotonergic receptors and thus produce selective effects on cortical function. PMID- 1754052 TI - Functional connections of the rat medial cortex and basal forebrain: an in vivo intracellular study. AB - Projections between the medial cortex and basal forebrain in the rat were demonstrated by intracellular recordings and the anterograde tracer Phaseolus vulgaris leucoagglutinin. Direct projections between these areas were indicated by antidromic action potentials, short latency (less than 5 ms) orthodromic potentials, and labeled axon terminals in the basal forebrain subsequent to iontophoresis of Phaseolus vulgaris leucoagglutinin into posterior cingulate cortex. High proportions of antidromic action potentials were encountered in responsive cortical neurons (66%) and basal forebrain neurons (97%). Antidromic latencies recorded in the basal forebrain (less than 1.0 ms) revealed fast ascending projections; cortical neurons showed both fast and slow descending projections (latencies of 0.3-3.7 ms). Relatively few synaptic potentials (none in the diagonal band of Broca) and sparse labeling of axon terminals observed in the basal forebrain indicated that the ascending projections may be the more physiologically important or, at least, densest pathway. Polysynaptic feedforward pathways were suggested through long latency (greater than 20 ms) inhibitory and excitatory postsynaptic potentials, the former being the more common response. Candidate inhibitory neurons were identified in both cortex and basal forebrain. Possible monosynaptic (less than 5 ms) inhibitory postsynaptic and antidromic responses in these cells provided evidence that candidate inhibitory neurons participate in the reciprocal pathways. PMID- 1754053 TI - Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the regional distribution of brain monoamines in the rhesus monkey. AB - In an attempt to define neurochemically the part played by 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) as a potential Parkinson's disease-inducing neurotoxin, we measured the tissue concentrations of the monoamines dopamine, noradrenaline and serotonin in 45 brain regions in nine rhesus monkeys (Macaca mulatta) receiving repeated intramuscular injections of a total amount of 2.1-7.5 mg/kg MPTP-HCl. Four monkeys treated with MPTP during a period of one to five weeks developed permanent Parkinsonism, and five animals receiving the neurotoxin during a period of two to seven months remained asymptomatic. We found that, compared with the distribution pattern established in the brain of seven normal (drug-free) rhesus monkeys, in the MPTP-treated monkeys none of the three major brain monoamine neuron systems was completely resistant to the neurotoxin. In addition, each brain monoamine had a characteristic regional pattern of MPTP induced changes. As expected, the most significant alterations were found within the nigrostriatal dopamine system, i.e. profound dopamine loss in caudate nucleus, putamen and substantia nigra. However, many extrastriatal regions of the subcortex and brainstem also suffered significant loss of dopamine, with the noradrenaline loss in the regionally subdivided brainstem being less widespread, and the serotonin levels least affected. Thus, in subcortex/brainstem the ranking order of sensitivity to MPTP was: dopamine greater than noradrenaline much greater than serotonin. In the cerebral (neo- and limbic) cortex, all three monoamine neuron systems suffered widespread statistically significant losses. The ranking order of MPTP sensitivity of the cortical monoamines was: noradrenaline greater than serotonin greater than dopamine. In the cerebellar cortex, dopamine and noradrenaline concentrations were significantly reduced, whereas the serotonin level remained unchanged. A remarkable observation was that many of the subcortical and cortical changes found in the symptomatic monkeys were also found in the asymptomatic animals. Our data are compatible with several possible mechanisms by which MPTP may have produced the observed patterns of monoamine loss in the brain of the rhesus monkey. Our study demonstrates that in the rhesus monkey MPTP mimicked, in addition to the profound striatal dopamine loss, some of the extrastriatal dopamine, noradrenaline and serotonin changes often seen in the brain of patients with idiopathic Parkinson's disease. However, using our treatment regimen, we have not been able to reproduce in the rhesus monkey the inter-regional pattern of striatal dopamine loss typical of idiopathic Parkinson's disease, i.e. a significantly greater loss of dopamine in the putamen compared with the caudate nucleus. PMID- 1754054 TI - Acetylcholine release in the rat hippocampus as measured by the microdialysis method correlates with motor activity and exhibits a diurnal variation. AB - Extracellular levels of acetylcholine were measured by the microdialysis method coupled to high performance liquid chromatography in the dorsal hippocampus of freely moving rats over a period of 24 h to examine whether the acetylcholine release in the hippocampus exhibited a diurnal variation. Spontaneous motor activity was simultaneously measured with an automatic animal activity monitor. The amount of acetylcholine collected per 20-min sample varied markedly, in a range from about 5 to 90 pmol. There appeared to be variations in the amount with a 2-4 h periodicity as well as an apparent diurnal periodicity. In all five rats studied, the overall mean value for the dark cycle (11.1-34.5, average 20.9 pmol/20 min) was significantly greater than that for the light cycle (5.1-21.3, average 12.3 pmol/20 min), showing a 70% average increase. Cross-correlation analysis performed between the amount of acetylcholine and the motor activity count for the animal during the sampling revealed a significant positive correlation coefficient in four rats studied. The present study demonstrates for the first time that the acetylcholine release shows a diurnal variation. PMID- 1754055 TI - Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system. AB - The distribution of transforming growth factor-beta isoforms 1, 2 and 3 and transforming growth factor-beta 2 and 3 mRNAs in adult rat central and peripheral nervous system was examined using Northern blotting and isoform specific antibodies for immunocytochemistry. Transforming growth factor-beta 2 and 3 mRNA were present in all brain areas including cerebral cortex, hippocampus, striatum, cerebellum and brainstem. In sciatic nerve, transforming growth factor-beta 3 mRNA was highly expressed, but transforming growth factor-beta 2 mRNA was not detectable. Transforming growth factor-beta 1-like immunoreactivity was confined to meninges and choroid plexus in the brain and connective tissue in peripheral ganglia and nerves. Transforming growth factor-beta 2 and 3 immunoreactivity entirely overlapped and, in general, were found in large multipolar neurons. Highest densities of immunoreactive neuronal perikarya were present in spinal cord and brainstem motor nuclei, hypothalamus, amygdaloid complex, hippocampus and cerebral cortical layers II, III and V. Most thalamic nuclei, superior colliculi, periaqueductal gray and striatum were almost devoid of transforming growth factor-beta 2- and 3-immunoreactive neurons. Fibrous astrocytes in white matter areas were intensely immunostained. Most dorsal root ganglionic neurons, their satellite cells and Schwann cells in peripheral nerves were also labeled. Transforming growth factor-beta 2- and 3-immunoreactive neurons were localized in brain regions that have been shown to contain neurons synthesizing and/or storing basic fibroblast growth factor suggesting possible opposing or synergistic effects of these peptide growth factors. However, the precise functions of local synthesis and storage of the transforming growth factor-beta isoforms in the nervous system are as yet unknown. PMID- 1754056 TI - Acupuncture-evoked responses of subnucleus reticularis dorsalis neurons in the rat medulla. AB - Recordings were made from neurons in subnucleus reticularis dorsalis of the rat. Two populations of neurons could be distinguished: those with total nociceptive convergence which were driven by activating A delta- and C-fibers from any part of the body and those with partial nociceptive convergence which were driven by activating A delta-fibers from any part of the body or C-fibers from some, mainly contralateral, regions. The effects on subnucleus reticularis dorsalis neurons of manual acupuncture, performed by a traditional Chinese acupuncturist at the "Renzhong", "Sousanli", "Changqiang", and "Zusanli" acupoints and at a non acupoint next to "Zusanli", were studied. Acupuncture stimulation for 30 s at the acupoints or the non-acupoint strongly excited all the total nociceptive convergence neurons tested; these neurons responded with a discharge of rapid onset which was often followed by after-discharges lasting for approximately 30 60 s. The majority but not all of the partial nociceptive convergence neurons responded to 30 s of acupuncture stimulation at the acupoints or the non acupoint. This was especially the case when the stimulus was applied to contralateral or midline parts of the body. The potency of acupuncture as a means of activating subnucleus reticularis dorsalis neurons varied significantly with the area of the body being stimulated such that: contralateral greater than midline greater than ipsilateral areas. The levels of induced activity were of similar magnitude to those evoked by noxious mechanical stimuli applied under identical experimental conditions. No differences were found between the capacities to activate subnucleus reticularis dorsalis neurons of the "Zusanli" point and the adjacent non-acupoint, no matter whether these were stimulated ipsi or contralaterally; this suggests a lack of topographical specificity in the activation of these neurons. Since subnucleus reticularis dorsalis neurons are activated exclusively or preferentially by noxious inputs, it is concluded that the signals elicited by manual acupuncture travel through pathways responsible for the transmission of nociceptive information. Since acupuncture, a manoeuvre which is known to elicit widespread extrasegmental antinociceptive effects, activates subnucleus reticularis dorsalis neurons which, anatomically, send dense projections to the dorsal horn at all levels of the spinal cord, we would suggest that this structure may be involved not only in signalling pain but also in modulating pain by means of spino-reticulo-spinal feed-back mechanisms. PMID- 1754057 TI - Immunohistochemical evidence that acetylcholine and glycine exist in different populations of GABAergic neurons in lamina III of rat spinal dorsal horn. AB - Pre-embedding immunohistochemistry with monoclonal antibody to choline acetyltransferase was combined with post-embedding immunohistochemistry with antisera to GABA and glycine in order to study the pattern of coexistence of GABA, glycine and acetylcholine in neurons in lamina III of rat spinal dorsal horn. Of 50 neurons which were choline acetyltransferase immunoreactive, 47 showed GABA-like immunoreactivity and none were immunoreactive with antiserum to glycine, despite the fact that glycine is thought to be present in the majority of GABAergic neurons in lamina III. This suggests that while acetylcholine and glycine can both coexist with GABA in lamina III neurons, they are present in different populations of GABAergic cells. Taken together with recent ultrastructural evidence concerning the synaptic connections of glycinergic and cholinergic structures in the dorsal horn, this suggests that there are functional differences between neurons which contain GABA and glycine and those which contain GABA and acetylcholine. PMID- 1754058 TI - Synaptic efficacy of inhibitory synapses in the reinnervating hypoglossal motoneurons. AB - The synaptic efficacy of inhibitory synapses in tongue protruder motoneurons reinnervating the tongue retractor muscle was studied in cats. We have demonstrated that the percentage magnitude of a short- and a long-lasting inhibitory postsynaptic potential in the inhibitory postsynaptic potentials produced in the tongue protruder motoneurons, whose axons had been cut but allowed to regenerate to make functional contact with the tongue retractor muscles, by lingual nerve or inferior alveolar nerve stimulation, was rearranged to appear like that exhibited by the tongue retractor motoneurons that normally supply that muscle. In addition, the peak amplitude of the summated afterhyperpolarization in a tongue protruder motoneuron on operated cats at nine months axon-union was in the normal range. PMID- 1754059 TI - Monoamine oxidase B in brains from patients with Alzheimer's disease: a biochemical and autoradiographical study. AB - In vitro quantitative autoradiography using [3H]L-deprenyl, an irreversible and preferential inhibitor of monoamine oxidase B, was performed to investigate the localization of the enzyme in brains from senile dementia of Alzheimer type and control cases. Brains from three male patients with the clinical diagnosis of senile dementia of Alzheimer type and from three male control patients, without any known clinical history of neurological disorder, were obtained at autopsy. Cryosections of 100 microns thickness were mounted on gelatinized glass plates and dried over desiccant for one week at -20 degrees C. The sections were incubated with 10 nM [3H]L-deprenyl for 1 h and then exposed to film for four weeks. The autoradiographs were analysed by computer-assisted densitometry. Monoamine oxidase-B activities were also estimated in 1% homogenates from 10 different regions, using 10 microM beta-[ethyl-14C]phenylethylamine, in order to study the consonance between the autoradiographical and biochemical techniques. Both [3H]L-deprenyl binding and monoamine oxidase-B activities in senile dementia of Alzheimer type were higher than in the controls in all brain regions studied. The increase was highest in the white matter (about 70%) and in the order of 20 50% in the various gray matter regions. A high correlation coefficient (r approximately 0.9) was obtained between [3H]L-deprenyl binding and monoamine oxidase-B activity, both in the senile dementia of Alzheimer type and in the control brains. PMID- 1754060 TI - Distribution of intracerebrally injected dopamine as studied by a punch scintillation modeling technique. AB - Three-dimensional distribution gradients of intracerebrally injected tritiated dopamine were calculated on the basis of concentrations in multiple punch-samples from sequential sections of Macaca fascicularis brain tissue. The monkey was pretreated systemically with a monoamine oxidase inhibitor to retard elimination. Gradients were best fit by cubic exponential equations relating concentration to distance from the center of the site. The concentration at the center, total amount of label, and total extent of the site injected just before perfusion were consistent with initial distribution in the extracellular space, if the volume fraction of the latter is estimated at 20%. The extent of distribution was distinctly greater in the mediolateral and dorsoventral dimensions than in the anteroposterior dimension. The total amount of label near the site decreased rapidly in the first few minutes after injection, then much more slowly, reaching about 30% of the injected amount after 2 h. Its distribution within the site changed steadily, the outer boundary gradually expanding and the peak at the center gradually decreasing. This pattern was consistent with an initial rapid dispersion by injection pressure and an initial loss of tritiated dopamine due to disruption of the blood-brain barrier at the center of the site, followed by a steady expansion of the site driven by diffusion and bulk flow. PMID- 1754061 TI - Striatal neurons express increased level of dopamine D2 receptor mRNA in response to haloperidol treatment: a quantitative in situ hybridization study. AB - In the present study, quantitative in situ hybridization was used to analyse the effect of haloperidol treatment on D2 dopamine receptor gene expression in the rat caudate-putamen nucleus. Variations of D2 receptor mRNA level were studied and measured at the macroscopic level of densitometric analysis of X-ray film and at the microscopic level by counting of autoradiographic silver grains in striatal cells. Macroscopic analysis demonstrated that haloperidol treatment two times 1 mg/kg per day during seven, 14 and 21 days increased D2 receptor mRNA level in the caudate-putamen. Detailed microscopic analysis demonstrated a significant increase in D2 receptor mRNA in the two neuronal populations known to express the D2 receptor gene: medium-sized neurons previously identified as enkephalinergic neurons, and large-sized neurons previously identified as cholinergic neurons. The increase was more important in cholinergic neurons (+119%) than in enkephalinergic neurons (+54%). Haloperidol treatment did not modify the number of medium-sized enkephalinergic neurons expressing the D2 receptor mRNA. In contrast, it significantly increased the percentage of large sized neurons containing D2 receptor mRNA (from 80 to 94%). These results demonstrate that haloperidol treatment acts at the gene level to modulate D2 receptor content in striatal dopaminoceptive neurons, and that the D2 receptor mRNA increase in postsynaptic neurons contributes to dopamine supersensitivity induced by neuroleptics in the rat. This suggests that dopamine acts trans synaptically to control D2 receptor gene expression in target striatal neurons. These results suggest that modifications of D2 receptor gene expression may be part of the biological events that lead to the movement disorders induced by neuroleptic drugs or Parkinson's disease. PMID- 1754062 TI - Peripheral projections of the chick primary sensory neurons expressing gamma aminobutyric acid immunoreactivity. AB - The expression of gamma-aminobutyric acid was studied in sensory neurons and peripheral target tissues of the chick dorsal root ganglia by combining immunocytochemistry and electron microscopy. In the chick embryos, the first immunoreaction was observed at embryonic day 12 in 1.4% of ganglion cell bodies. The intensity of immunostaining gradually increased during development and the percentage of immunostained neurons reached an average of 7.3% after hatching. These immunostained cell bodies could be identified as sensory neurons belonging either to some large neurons of the A1 subclass or to a few small neurons of the B1 subclass. The other neuronal cell bodies, corresponding to the A2 and B2 subclasses, as well as the satellite and glial cells were apparently devoid of any gamma-aminobutyric acid immunostaining. Among the peripheral tissues innervated by the primary sensory neurons, the nerve endings of Achilles' tendon and the paravertebral autonomic ganglia appeared devoid of immunoreactivity. In contrast, immunoreactivity was found within nerve endings located in some neuromuscular spindles of the skeletal muscles and within some Herbst's corpuscles in the subcutaneous tissue of the skin. Thus, the present results provide evidence that gamma-aminobutyric acid may be expressed by neuronal cell bodies belonging to two subclasses of primary sensory neurons and could be a putative neurotransmitter involved in the peripheral sensory innervation of, at least in part, skin and skeletal muscles. PMID- 1754063 TI - Thrombin indirectly affects cholinergic cell expression in primary septal cell cultures in a manner distinct from nerve growth factor. AB - The effects of thrombin were examined in primary cultures of dissociated medial septal cells from fetal (embryonic day 17) rat brains. Seven days of continuous exposure of these cultures to thrombin produced a dose-dependent increase in the activity of the enzyme choline acetyltransferase (EC 2.3.1.6) and no change in the number of acetylcholinesterase (EC 3.1.1.7)-positive cells. Maximal induction of choline acetyltransferase activity occurred around 1-2 nM thrombin and was first detected after five days of treatment. In addition, thrombin promoted neuronal cell aggregation, proliferation of the astroglia, and changes in astroglial cell morphology. Neuronal aggregation was first noted after 24 h of treatment, while the proliferative response of the astroglia was first apparent after four days of treatment, slightly prior to the increase in choline acetyltransferase enzymatic activity. In order to see if the induction of the enzyme choline acetyltransferase was dependent upon the astroglial cell response, we included the anti-mitotic agent 5-fluoro-2'-deoxyuridine, to find that astrocyte proliferation, as well as thrombin-induced increase in choline acetyltransferase, were both abolished. In contrast, the aggregation of neurons was not affected. Finally, thrombin-induced changes in choline acetyltransferase could not be antagonized by immunoneutralizing anti-nerve growth factor antibodies and when thrombin was added simultaneously with 100 ng/ml 2.5-S nerve growth factor, the increase in choline acetyltransferase activity was additive. In conclusion, it appears that thrombin affects cholinergic septal neurons indirectly via the responsive astrocytes in a manner distinct from nerve growth factor. PMID- 1754064 TI - The emergence of electroreceptor organs in regenerating fish skin and concurrent changes in their transduction properties. AB - The process of regeneration of skin patch denervated empullary electroreceptor organs of the African catfish Clarias gariepinus has been investigated at an ambient temperature of 28 degrees C with both electrophysiological and histological methods. At day 1 after denervation none of the receptor organs on the skin patch showed afferent activity. At this stage none of the ampullary organs previously recorded showed a normal appearance. Degenerative changes consisted of a decreased number of receptor cells and an often invisible lumen. At day 7 regeneration seems to start with a high density of primordial ampullary organs, more than a seven-fold increase compared to controls. In these units, the level of spontaneous activity is very low: compared to controls, more than a two fold increase in mean interspike interval. At this stage, the sensitivity to electrical stimuli is already at the level of untreated control organs. At day 15 there is a lower, i.e. approximately normal, density of ampullary organs with a normal morphology. In these units both spontaneous firing and sensitivity returned to normal. It can be concluded that the functional dichotomy between spontaneous firing and sensitivity that was found in degenerating ampullary electroreceptor organs is also found during the process of their regeneration, although the underlying cellular changes may be totally different. The speed of recovery suggests that only regeneration of the distal part of the sectioned nerve fibers takes place. PMID- 1754065 TI - Prostaglandin E2 changes in the retina and optic nerve of an eye with injured optic nerve. AB - Changes in arachidonic acid metabolism were studied in the optic nerve, the chorioretina, and in the vitreous following crush injury to the optic nerve of rats. Crush injury led to: (i) a 3.9-fold increase in optic nerve prostaglandin type E2 in vitro production which peaked on day 5 and was followed by a gradual decline, but was still significantly higher than baseline levels by day 12; (ii) a two-fold increase in the chorioretina prostaglandin type E2 in vitro production which peaked on day 1, and resumed baseline levels by day 3; (iii) a 3.5-fold increase in vitreous prostaglandin type E2 levels on day 1 which remained at 1.5 2 times higher than baseline levels for the rest of the study period (12 days). The findings indicate that the pattern of changes in prostaglandin type E2 production by the optic nerve (consisting mostly of white matter) is different from that described for injured brain tissues. The prolonged accumulation of vitreal prostaglandin type E2 in eyes with damaged optic nerve may lead to undesirable effects on the retina beyond those directly manifested in the retina by altered axonal flow in the injured optic nerve. PMID- 1754066 TI - Immunohistochemical and ultrastructural studies of the various nuclei of the trigeminal complex in the human newborn. AB - The various nuclei of the trigeminal complex were studied by immunohistochemical (enkephalin localization) and ultrastructural means in the brainstems of eight newborn human babies that died within 24 h after birth. Positive enkephalin neurons were detected in the chief sensory and spinal trigeminal nuclei as well as in some fibers of the trigeminal nerve. Ultrastructurally, two morphologically distinct types of neuron were observed, respectively, in the motor nucleus, the spinal nucleus and the mesencephalic nucleus of the trigeminal complex, whereas three morphologically distinct types of neuron were observed in the chief sensory nucleus. "Glomerulus" formation was a frequently observed feature in the chief sensory nucleus. In the spinal nucleus, rolls of synaptic terminals stacking up one on top of another and synapsing onto the final synaptic element were very much in evidence. Axosomatic, axodendritic, dendrodendritic and dendroaxonic synapses were demonstrated in all the different nuclear areas of the trigeminal complex but axoaxonic synapses were absent in the mesencephalic nucleus. Some of the findings in the present human study were similar to those reported in the rats and cats. PMID- 1754067 TI - Microtubule-associated protein-2 and neurofilament immunoreactivity in neurons and small, intensely fluorescent cells of an amphibian cardiac ganglion. AB - The localization of two cytoskeletal proteins was analysed in the cell bodies and processes of ganglionic neurons and small, intensely fluorescent cells of the parasympathetic cardiac ganglion of Necturus maculosus (mudpuppy). Antibodies against microtubule-associated protein-2 and against the highly phosphorylated isoforms of high and middle molecular weight neurofilament subunits were used as somatodendritic and axonal markers, respectively. The ganglionic neurons, which usually have only one major process, and small, intensely fluorescent cells, which have several processes, showed distinctly different staining patterns with the two antibodies. In control and denervated ganglia, the ganglionic cell bodies and several hundred micrometers of the proximal processes were labeled with the antibody against microtubule-associated protein-2, whereas small, intensely fluorescent cells and processes showed a paucity of immunoreactivity. The neurofilament antibody labeled numerous axons in the ganglion but did not label the proximal part of the postganglionic process or small, intensely fluorescent cell processes. Denervation resulted in the presence of phosphorylated neurofilament subunit immunoreactivity in the soma and proximal process of the ganglionic neuron. These data suggest that (i) small, intensely fluorescent cells and ganglionic neurons in the mudpuppy cardiac ganglion contain distinctly different cytoskeletal proteins, (ii) the proximal part of postganglionic "axons" contains dendrite-like and not axon-like cytoskeletal proteins, and (iii) deafferentation promotes the localization of phosphorylated forms of neurofilament subunits in the soma and proximal process of parasympathetic ganglionic neurons. PMID- 1754068 TI - Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. AB - N-Acetyl-aspartate is found in high concentrations in all areas of the brain, but is undetectable in non-neuronal tissue. In order to characterize the cellular localization of N-acetyl-aspartate in brain, highly specific monoclonal antibodies against N-acetyl-aspartate were produced by fusing spleen lymphocytes obtained from mice immunized with N-acetyl-aspartate conjugated to thyroglobulin by carbodiimide with P3/x63-Ag8.653 mouse myeloma cells. Clones were selected which secrete IgG2a(k) antibodies highly specific for conjugated N-acetyl aspartate. Only 3-6% cross-reactivity with conjugated N-acetyl-aspartate glutamate was observed at high antibody concentrations, whereas no cross reactivity (less than 1%) was observed with conjugated N-acetyl-glutamate or aspartate. Preincubation of the antibodies with 0.5 mg/ml conjugated N-acetyl aspartate blocked immunoreactivity more than 90%, while preincubation with conjugated N-acetyl-aspartate-glutamate and free N-acetyl-aspartate had no effect. Immunocytochemical staining has shown that N-acetyl-aspartate-like immunoreactivity is localized in neurons, which are widely distributed throughout the brain. The immunoreactive neurons exhibited intense staining of the perikarya, proximal dendrites and axons. No consistent pattern of distribution of immunoreactivity was observed with regard to primary neurotransmitter characteristics of stained neurons although neurons with long projections or extensive arbors, such as pyramidal cells in cortex, locus coeruleus, motor neurons and Purkinje cells, stained much more intensively than local circuit neurons. PMID- 1754069 TI - Repeated electroconvulsive shock increases tachykinin and cholecystokinin mRNA expression in ventral periaqueductal gray. AB - The effect of repeated electroconvulsive shock (five shocks during 10 days) on preprocholecystokinin and preprotachykinin-A messenger RNA expression was studied in the mesencephalic periaqueductal gray and adjacent areas of rat using in situ hybridization histochemistry with specific oligonucleotide probes. An increased number of preprocholecystokinin and preprotachykinin-A messenger RNA hybridization positive neurons (+30% and +47%, respectively) in the Edinger Westphal nucleus was observed following repeated electroconvulsive shock. In addition, both preprocholecystokinin and preprotachykinin-A messenger RNA expression, measured as grain density over single neurons, was significantly increased (+37% and +45%, respectively). The results indicate that cholecystokinin- and substance P-containing neurons in the Edinger-Westphal nucleus are activated by repeated electroconvulsive shock, which may be related to the antidepressant and analgesic effects of electroconvulsive shock treatment. PMID- 1754070 TI - Dual determination of extracellular cholecystokinin and neurotensin fragments in rat forebrain: microdialysis combined with a sequential multiple antigen radioimmunoassay. AB - Microdialysis was combined with a highly sensitive sequential multiple antigen radioimmunoassay to simultaneously measure extracellular cholecystokinin and neurotensin fragments from discrete regions of the rat brain in vivo. The assay was conducted in 96-well plates and provided a limit of detection for both peptides of 0.1 fmol. Dialysis membranes composed of polyacrylonitrile, Cuprophan and polycarbonate were evaluated in vitro using both radiolabelled peptides and radioimmunoassay. Polycarbonate probes were implanted in the posterior medial nucleus accumbens-septum, medial caudate nucleus or medial prefrontal cortex of halothane-N2O-anaesthetized rats. Cholecystokinin immunoreactivity levels were generally above the assay detection limits (0.1-0.7 fmol) in 30-min samples from all three regions under basal conditions. Recovered basal amounts of neurotensin immunoreactivity were detectable in the nucleus accumbens-septum in approximately 50% of experiments (0.1-0.2 fmol) but were not measured in the caudate nucleus or prefrontal cortex. In the nucleus accumbens-septum, a 10-min pulse of 200 mM K(+) containing artificial cerebrospinal fluid in the perfusion medium during a 30-min sampling period increased the recovered cholecystokinin and neurotensin immunoreactivity to 9.7 fmol +/- 1.9 S.E.M. and 5.8 +/- 1.6 S.E.M., respectively. A second stimulation following a 2.5-h interval produced similar elevations with S2:S1 ratios of 0.62 +/- 0.07 and 0.68 +/- 0.07 for cholecystokinin and neurotensin, respectively. In a separate series of experiments the second stimulation of both peptides was prevented by perfusion of a 10 mM EGTA containing medium. Similar results were obtained in the caudate nucleus for cholecystokinin, but K(+)-induced elevations in neurotensin immunoreactivity were much smaller (0.5 fmol) in this brain region and calcium dependency was not established. Sequential K+ stimulations at 50, 100 and 200 mM produced progressively greater increases in recovered cholecystokinin and neurotensin immunoreactivity from the nucleus accumbens-septum and of cholecystokinin immunoreactivity from the prefrontal cortex. No neurotensin immunoreactivity was detected in the prefrontal cortex following K+ stimulation. Large post mortem increases in the recovered amounts of cholecystokinin and neurotensin immunoreactivity were observed. This effect was significantly attenuated by EGTA although there was a large calcium-independent component of the cholecystokinin immunoreactivity. On reverse-phase high-performance liquid chromatography the major cholecystokinin-immunoreactive peak co-eluted with sulphated cholecystokinin octapeptide. Neurotensin-immunoreactive material co-eluted with neurotensin (1-13), neurotensin (1-12), neurotensin (1-11), neurotensin (1-10) and neurotensin (1-8). These results further demonstrate the potential of microdialysis for studying neuropeptide release and metabolism in vivo when combined with sufficiently sensitive assay procedures. PMID- 1754071 TI - [Arterio-jugular difference of oxygen and intracranial pressure in comatose, head injured patients. I. Technical aspects and complications]. AB - The monitoring of the comatose head injured patients is based on the recording of several data; the intracranial pressure measurements (ICP), associated with the arterial pressure recording, gives a good estimate of the cerebral perfusion pressure (CPP) but further information about the cerebral perfusion are needed. Based on the assumption that the cerebral metabolic rate is kept constant strong relationships exist between the cerebral blood flow (CBF) and the arterovenous difference of oxygen (AVDO2). In order to obtain samples of cerebral venous blood a catheter must be inserted in the internal jugular vein (IJ) with the tip of the cannula reaching the superior jugular bulb. In 224 patients we measured the ICP trough ventricular or subdural catheters; invasive measurement of the arterial pressure was also carried on in all the patients. In 45 patients we measured the AVDO2 and we tested the safety and the reliability of the jugular vein cannulation. During the insertion of the jugular catheters a slight increase of ICP, without any clinical significance, was recorded; in two cases (on a total of 45) accidental carotid puncture occurred. In 9 cases we tested the concordance of the oxygen content between the two IJs; looking at the mean values no statistical difference is detected between the two sides but in some cases relevant differences are recorded. In two cases we inserted the catheters more cranially, reaching a sinus of the cranial basis; the blood collected from these points carries less oxygen that the blood collected in the neck. The rate of infection in this series of ICP monitoring is very low (1.78%) and we had no bleeding at the moment of the insertion of the catheters. Since no significant complications related to the IJ cannulation were recorded we conclude that these techniques are safe and can be easily performed in the clinical setting. Further studies are required in order to investigate the clinical meaning of the differences in the IJs content of oxygen. PMID- 1754072 TI - [Arterio-jugular difference of oxygen and intracranial pressure in comatose, head injured patients. II. Clinical correlations]. AB - The ICP monitoring is currently used in the treatment of the head injured patients in order to avoid dangerous increases of the pressure and critical reduction of cerebral perfusion pressure (CPP). The cerebral blood flow is dependent on the CPP and is kept constant, under normal circumstances, by autoregulation. When autoregulation is impaired or overwhelmed oxygen delivery becomes uncoupled to the metabolic needs of cerebral tissue: in such a condition the rate of oxygen extraction changes and the artero-jugular difference for O2 (AVDO2) reflects this change. The AVDO2 can be used as an estimate of the CBF and can detect a situation of hyperemia (low AVDO2) or ischemia (high AVDO2). In 224 comatose head injured patients the ICP was measured using ventricular or subarachnoid catheters: the CPP was continuously assessed and the outcome was evaluated six months after the trauma. In 45 patients the AVDO2 was studied and the data were corrected for a PaCO2 of 40 mmHg and investigated. The severity of the ICP is decisive for the prognosis and, accordingly, the number of times the CPP is below 60 mmHg plays a major role in the outcome. The mortality rate was 21% for the patients without ICP greater than 20 mmHg and 54% for the patients with severe increases in ICP. The mean values of AVDO2 were low, ranging around 4.6 vol%; only 4 patients showed some temporary evidence of ischemia, as assessed by an AVDO2 greater than 8 vol%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754073 TI - [Hypomagnesemia and hypokalemia as risk factors of arrhythmia in acute phase myocardial infarction]. AB - In a uniform group of 30 patients the A. have assessed the incidence of lower serum K+ and Mg++ concentrations on the probability of arrhythmias onset in the acute phase of myocardial infarction. The study shows that lower K+ and Mg++ levels significantly influence only the onset of ventricular tachycardia and monofocal PVC. PMID- 1754074 TI - [Survival of 213 patients who recovered in resuscitation from cardiac arrest]. AB - 213 patients who received in-hospital cardiopulmonary resuscitation (CPR) were studied over a period of five years (1985-89) to determine hospital and long-term survival. The following factors were evaluated in determining outcome: age, ECG on admission, clinical history, year, month, hour of admission. A 5-year survival table was complied for all discharged from hospital. The results showed that age, clinical history, month and hour of admission were not influencing factors; asystole as opposed to ventricular fibrillation was however associated with significantly higher in-hospital mortality (p less than 0.005). Hospital survival was 14.6% with an ascendant range from 1986 to 1989 (p less than 0.05); all the patients were discharged mentally unimpaired with over 50% surviving 1.5 years after discharge and 33% 5 years after. The study shows that the highest cause of cardiac arrest is ischaemic cardiopathy in male patients with an average age of 60 years. Total neurological recovery after CPR was confirmed to be a determinant predictor factor of survival. PMID- 1754075 TI - [Anesthesiologic problems in excessive obesity]. AB - Clinical problems to consider in excessive obesity are numerous. Careful preparation before surgery is indispensable to reduce complications during and after surgery. Choice of volatile anesthetic may be important for the good results of narcosis. In the reported case anesthetic management is considered in an obese patient who had undergone a gastric operation. PMID- 1754076 TI - [General balanced anesthesia and propofol in ablation of the arterioventricular junction]. AB - The Authors compare the results of general balanced anaesthesia and propofol in the anaesthetic management of closed-chest ablation of A-V junction. The best results were obtained with propofol because of the lower incidence of cardiovascular complications. Therefore propofol is a suitable agent in the anaesthetic management of closed-chest ablation of the A-V junction. PMID- 1754077 TI - [Propofol in single bolus for treatment of elevated intracranial hypertension]. AB - Eleven patients with intracranial pressure (ICP) above 20 mmHg despite hyperventilation and neurosedation were treated with a bolus of propofol (1.5 mg/kg) i.v. At baseline and 1-2-5-10-15-30-45 minutes after propofol administration we recorded the values of PIC, systolic arterial pressure (SAP) and mean arterial pressure (MAP), heart rate (HR) and cerebral perfusion pressure (CPP), calculated as MAP less PIC. In the first ten minutes after propofol we observed a statistically significant (p less than 0.05) decrease of ICP and SAP. MAP decreased in the first five minutes only. Consequently HR increased at the same time. CPP decreased in the first two minutes after administration of the drug, but without statistical evidence. We conclude that propofol, in our opinion, can be used to treat intracranial hypertension but the hemodynamic effects in hypovolemic patients must be taken into consideration. PMID- 1754078 TI - [Intraoperative radiotherapy: anesthesiologic problems during transport of patients]. AB - In this study the condition of anesthesia in 8 patients, undergoing intraoperative radiation therapy (IORT) for pancreatic or rectal tumors, is evaluated. Patients with reapproximated surgical incision were transferred from the operating room to the radiotherapy department while still under anesthesia. The risks of such transport as well as guidelines for the patient's care during this phase are examined. The results of this study indicate that in order to move anesthetized patients safely it is necessary to ensure stable cardiovascular, respiratory and metabolic conditions prior to their transfer. It is also important to guarantee adequate analgesia and to establish appropriate monitoring during transport. PMID- 1754079 TI - [Use of buprenorphine after right hepatectomy]. AB - Ten patients who underwent surgery (5 right hepatectomy and 5 colectomy) for cancer participated in a clinical controlled study. They were treated with buprenorphine (i.v. slow infusion) to relieve postsurgical pain. We found an increased urinary excretion of this drug in patients who underwent hepatectomy as compared with patients who underwent colectomy. However no differences in the occurrence of side-effects and/or in the therapeutic effect were observed between the two groups. We conclude that buprenorphine can be effectively and safely used also in patients with a resection of liver parenchyma. PMID- 1754080 TI - [Recovery after serious mushroom poisoning (grade IV encephalopathy) with intensive care support and without liver transplantation. Clinical case]. AB - Despite consistent improvement in its treatment, amatoxin poisoning still extolls an elevated overall mortality, ranging between 10 and 15%, which approaches 100% when severe (grade 3-4 encephalopathy) hepatic failure supervened. Therefore, the proper treatment of intoxication by amatoxin containing mushrooms, and particularly of its complications, remains a challenge in emergency medicine. Klein and coworkers reviewed the role of liver transplantation in amatoxin poisoning as a useful therapeutic tool for patients with severe impairment of liver function. Their indication for intervention is the presence of any of the following signs: grade 2 encephalopathy or higher; prothrombin time twice than normal, despite fresh frozen plasma infusion; hypoglycemia requiring hypertonic glucose infusion; hyperbilirubinemia (greater than 25 mg/dl). During the past autumn two patients with fulminant hepatic failure due to amatoxin poisoning were referred to our institutions as candidates for liver transplantation, since both satisfied Klein's criteria. However, due to shortage of organ donors it was impossible to transplant them over the following days. Despite they did not receive liver transplantation, both patients wakened from coma, their liver function improved, and they recovered from terminal amatoxin poisoning. After one year, both patients are long-term survivors, in good health and without any sequelae either in brain or liver function. PMID- 1754081 TI - [The length of pre- and postoperative surgical stays. The role of factors relative to the patient, to the type of intervention and to hospital services]. AB - The one-year most important and frequent surgical procedures performed in eight surgical departments of a large Italian general hospital were studied in order to describe the determinants of pre-, postoperative and total length of stay. The average length of stay (ALS) for the 724 hospitalized cases was 18.1 days (7.9 preoperative and 10.2 postoperative), with large variations in the preoperative ALS across the departments. Multiple regression analysis showed that total ALS was positively associated with age, type of surgical procedure and department of admission. Preoperative ALS was longer in intervention on colon (12 days) and stomach (11 days) than in saphenectomies (8 days) and in appendectomies (4 days). The degree of access to operating rooms was associated to preoperative ALS, while the type of intervention and age to postoperative ALS. ALS was reduced by the urgency of the case, the availability of diagnostic facilities in the department of admission and the patient's condition of student. Hospital's structure and organization need to be modified in order to reduce preoperative length of stay. The easier access of older patients to long-stay hospitals or home care would reduce postoperative length of stay. PMID- 1754082 TI - [Neoplasms of the major and minor salivary glands. The diagnostic and therapeutic approaches and case presentations]. AB - Between January 1982 and December 1988, 37 patients with neoplasm of salivary glands have been treated in our Division of Surgical Oncology. The sites of tumors were: parotid 26, submandibular gland 4, minor salivary gland 7. The preoperative diagnostic procedures were: sialogram, ultrasonogram, fine needle aspiration. Malignant tumors were 16:5 adenoca., 4 metastases, 3 adenoid cystic, 2 mucoepidermoid, 1 acinic cells, 1 lymphoma. Twenty-one patients affected by neoplasms and 5 by malignant tumors were treated with surgery only. Nine patients affected by malignant tumors were treated with surgery and RT. Two patients were treated with RT only. The first therapeutic step is surgery; in order to control local evolution of tumor, postoperative irradiation is recommended. Possible indications of preoperative diagnostic procedures and the therapeutic choices are discussed. PMID- 1754083 TI - [Surgery by exeresis for gastric carcinoma. An analysis of 165 consecutive cases]. AB - Surgery is still considered the best approach in gastric cancer. The aim of this study was to identify the most important factors involved in the determination of long-term survival. Total and subtotal gastrectomy were analysed. Long-term survival in these patients was strictly correlated with the stage of disease and the infiltration of resection margins. Early diagnosis is confirmed to be the most important factor in the long-term survival of these patients. PMID- 1754084 TI - [Colorectal carcinoma. A review of our cases]. AB - A retrospective study was carried out on patients who underwent surgery for colorectal carcinoma between January 1980 and December 1987 in order identify additional prognostic factors. A total of 203 patients were studied. The probability of survival in relation to time and other variables (sex, age, stage of disease) was assessed using Cox's proportional method with the aid of an EPILOG III statistics pack. The overall 60-month survival rate was 55% and no difference was found between colon and rectum. The following factors were taken into account as prognostic markers: the site of the carcinoma (colon or rectum), sex, age, the tract of the colon involved (right, transverse, left and sigma colon) and the stage of disease. None of these parameters, with the exception of the stage of disease, were statistically significant. On the contrary, the division into stages of disease showed a statistically significant difference in the 60-month survival curve which fell from approximately 80% for stages A, B1, B2 and B3 to 50% for stage C and to 0% for stage D. PMID- 1754085 TI - [Echography in the diagnosis of breast cancer]. AB - Fifty-one patients with clinically palpable breast cancer were examined using small-parts echotomography. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of overall diagnosis were assessed in the two groups of patients: T1 (diameter less than 2 cm) and T2-T3-T4 (diameter greater than 2 cm). The frequency of the main echographic signs associated with breast cancer was also investigated. Diagnostic accuracy was found to be high in the T2-T3-T4 group (93%), but very low in the T1 group (71%). The study confirms the importance of ultrasound as an additional test in the study of breast cancer. However, this method becomes increasingly less sensitive and specific as the size of the tumour decreases. PMID- 1754086 TI - [Thyroid carcinoma as cystic nodule. The diagnostic role of cytology by needle aspiration]. AB - 195 patients affected by a cystic thyroid lesion were studied by a Fine Needle Aspiration biopsy (FNAb). 42 patients were operated on account of clinical data, compressive phenomena or cytologic results suggesting a neoplasia. Out of the operated patients, 3 were affected by a carcinoma in the cystic lesion (one "pure" cystic nodule and two "mixed" ones), while three more patients with multinodular goiters showed a carcinomatous lesion in a nodule different from the cystic one. Macroscopic characteristics of the aspirated fluid (quantity and quality) didn't affect the cytologic diagnosis. Cytology was useful in the preoperative diagnosis of benign thyroid nodules (only two false positives out of 42 patients) and was diagnostic in all the three patients affected by a carcinoma in the cystic nodule. PMID- 1754087 TI - [Disabling outcomes and psychological disorders in the patient with an enterostomy]. AB - The authors carried out a retrospective study of patients undergoing enterostomy during the past 9 years. From 1981 to present a total of 60 patients (39 males and 21 females) were operated and subsequently followed-up. The aim of the study was to examine the following factors: the diagnosis which led to operation, the type of stoma used, early and late complications, the behaviour of the alvus, psychological disorders and Karnofsky's Performance-Status Index. After having presented the findings, the surgical results obtained are discussed together with the patient's psychological reactions to stoma. All types of early surgical complications were absent in 66.6% of patients, whereas late complications were absent in 41.6%. Even in those cases where surgical techniques and prostheses permitted a satisfactory post-operative outcome, the sociopsychological and sexual problems relating to the wound and the perceived difference between the real and ideal Ego are highlighted. PMID- 1754088 TI - [Leiomyosarcoma of the duodenum]. AB - The paper reports the case of a patient with leiomyosarcoma of the duodenum who underwent radical duodenocephalopancreatectomy and survived for 22 months after the operation. Following a review of the international literature on the topic, the diagnostic procedures and prognostic criteria of this uncommon tumour are discussed. In conclusion, leiomyosarcoma always presents considerable problems of diagnosis even with the aid of biopsy and only surgery can lead to recovery in a limited number of cases. PMID- 1754089 TI - [Relevance and therapeutic implications of dysplasia in the follow-up of ulcerative rectocolitis]. AB - Long standing ulcerative colitis (UC) is a condition capable of malignant transformation. Even if the rate of occurrence of carcinoma differs considerably among the various series, there is general agreement that it can be detectable in advance through the finding of glandular dysplasia. The Authors examine such a problem in a series of 27 patients submitted to clinical and endoscopic follow-up from 1984 to 1989. During this study a total of 237 rectosigmoidoscopies, 83 colonoscopies and 71 histologic exams were performed. At the outset mild or moderate dysplasia was found in 5 cases (18%). However, in the follow-up no evidence of dysplasia was detectable in 4 of the 5 cases. In the remaining case dysplasia was present only in one control. It was not found in the subsequent two histologic examinations. In our limited experience the incidence of dysplasia was not significant enough to require a prophylactic proctocolectomy. Instead a frequent and thorough endoscopic follow-up is recommended. PMID- 1754090 TI - [Embolism of the superior mesenteric artery. A clinical experience]. AB - The Authors report their clinical experience in superior mesenteric artery embolism: 10 arterial embolisms (71%) collected from a series of 14 obstructions of the superior mesenteric artery. The main interval from the beginning of the symptomatology to hospital admission was 48 h. Laparotomy was performed in all ten patients; gangrenous bowel was resected in 2 and 2 had an embolectomy of the superior mesenteric artery without intestinal resection. The remaining 6 patients had laparotomy alone and died. The Authors emphasize the difficulty in recognizing the disease at an early stage and suggest to contemplate in patients at risk with a persistent abdominal pain, the possibility of a superior mesenteric artery embolism. PMID- 1754091 TI - [Aneurysms of the abdominal aorta in elderly patients]. AB - Aneurysms of the abdominal aorta are often diagnosed in the over-75s. Although for many Authors the presence of risk factors such as cardiopathies, cerebrovascular problems, renal or respiratory insufficiency, which are clearly more frequent in elderly patients, represent a contraindication to the intervention of choice, personal experience has shown that surgery remains the best solution. In fact, in a group of patients operated on for aneurysm of the abdominal aorta in a heart, no significant differences in age-related mortality were observed. Surgery therefore remains the treatment of choice in the elderly too for it must also be remembered that the natural history of the disease has shown that, in a comparatively short time, the aneurysm ruptures and operating mortality is markedly higher. PMID- 1754092 TI - [Thrombectomy of the infra- and suprarenal cava to prevent pulmonary embolism in the presence of deep venous thrombosis. Personal experience with 11 surgically treated cases]. AB - DVT is a fairly frequent event and often fails to be recognised. Its main complication, pulmonary embolism, is the third cause of death in Italy with more than 70,000 deaths per annum. In the presence of infra- and suprarenal floating thrombi, cases in which the application of neither intraluminal nor extraluminal filters is indicated, the treatment of choice is thrombectomy with direct surgical access to the cava. Personal experience of 11 patients operated in the past 16 months with excellent surgical success is analysed. The indications and surgical techniques adopted are described. PMID- 1754093 TI - [Recovery after amputation for arteriosclerosis. Follow-up study]. AB - Clinical follow-up of 71 patients subjected to major amputation of the lower extremities for atherosclerotic arteriopathy has been analysed for the purpose of ascertaining real possibilities of functional recovery and quality of life. Research results show that only a small number of patients (38%) can achieve an acceptable quality of life. The reasons have been identified in the objective difficulty of adequate physical and psychotherapeutic rehabilitation owing to structural shortcomings or the presence of associated pathology or the advance in the basic condition which does not permit application or frustrates results. PMID- 1754094 TI - [The role of galactography in the diagnosis of breast diseases. Our experience]. AB - Following a description of the most common galactographic semeiotics in relation to the different types of secretion, the Authors report their personal experience in the use of galactography to diagnose breast cancer. Histopathological tests revealed the presence of carcinoma in 14 (29.2%) out of a total 48 galactographic examinations. In conclusion, the Authors underline the high degree of diagnostic precision of galactography, a test which contributes to the identification of a considerable number of carcinomas during the preclinical stage. PMID- 1754095 TI - [A new method of interpretation in the regulation of gastric secretion]. PMID- 1754096 TI - [Transverse mesocolon herniation. Description of a clinical case]. AB - A case of herniation of small bowel through a defect of the transverse meso-colon with secondary herniation through the gastrocolic ligament and re-entry into the greater peritoneal cavity is reported. This form of lesser sac hernia is rare and only one hundred half cases have been reported in literature. PMID- 1754097 TI - [Rare localization of a carcinoid tumor: the pancreas. A case report]. AB - Pancreatic carcinoid tumors are very rare. A case of obstructive jaundice caused by a large mass of the head of the pancreas is described. The histological examination of the surgical specimen revealed a pancreatic carcinoid tumor. A brief, discussion of the main characteristics of this kind of tumor is performed by the Authors. PMID- 1754098 TI - [A rare case of ileo-ileal intussusception secondary to adenocarcinoma of the small intestine in a 21-year-old adult]. PMID- 1754099 TI - [A case report of Castleman's disease in a patient with endometrioid adenocarcinoma of the ovary]. AB - The Authors report a case of Castleman's disease in a 45-year-old woman. She was admitted to hospital because of a thrombophlebitis of the left lower limb. An abdominal echotomography showed evidence of a mass with a diameter of about 6 cm at the pancreatic isthmus, and a cyst (diameter 25 mm) in the right ovary. An explorative laparotomy was performed and the masses were removed. Histological examination identified them respectively as a Castleman's disease of hyaline vascular type and an endometrioid carcinoma of the ovary. PMID- 1754100 TI - [A case of small intestinal leiomyosarcoma]. AB - The Authors report a case of leiomyosarcoma of the small bowel, a rare neoplasm with severe limitations of pre-operative diagnosis. A discussion of the pathological staging, diagnosis and surgical therapy follows. At the moment, better diagnostic techniques and greater awareness of the disease notwithstanding, the prognosis remains severe due to the presence of local or distant metastases at laparotomy. PMID- 1754101 TI - [Verrucous carcinoma of the penis. A case report and review of the literature]. AB - The Authors report a case of a verrucous carcinoma of the penis. Among male malignant epithelial tumors the verrucous carcinoma represents a very rare form, with a typical oesophitic development, of vegetating sometimes ulcerated appearance, with slow evolution that rarely presents metastases. Although a therapeutic preservation approach is possible, a surgical operation is the treatment of choice. PMID- 1754102 TI - Type II diabetes mellitus: is the renal risk adequately appreciated? PMID- 1754103 TI - Tubular dysfunction in nephrotic syndrome: incidence and prognostic implications. AB - Although some cases of tubular dysfunction (TD) associated with nephrotic syndrome have been described, the incidence and the characteristics of this complication remain unknown. We investigated the presence of TD (renal glycosuria, aminoaciduria, metabolic acidosis with normal anion gap, hypouricaemia, and throughout hypophosphataemia) in 36 patients with nephrotic syndrome. Ten patients (group 1) showed glycosuria at some time during the course of their illness, ranging from 2.5 to 11.2 g/24 h. In addition, seven of them had metabolic acidosis with normal anion gap, five aminoaciduria, and two hypouricaemia. Membranous glomerulonephritis was the most frequent aetiology in group 1 patients (7 of 10). Proteinuria and serum creatinine (SCr) were significantly higher in group 1 patients than in the 26 remaining patients without TD (group 2): 10.2 +/- 3.7 versus 6.7 +/- 2.9 g/24 h (P less than 0.01) and 3.2 +/- 1.9 versus 1.6 +/- 0.9 mg/dl (P less than 0.05) respectively. The appearance of TD coincided with a clear worsening of renal function in most of group 1 patients. In addition, at the end of follow-up, SCr had increased from 3.2 +/- 1.9 to 5.6 +/- 3.3 mg/dl (P less than 0.05) in this group. In contrast, SCr did not show significant changes in group 2 (1.6 +/- 0.9 versus 2.1 +/- 2.2 mg/dl). In conclusion, a significant proportion (27.7%) of patients with nephrotic syndrome present TD data at some moment of their course; the appearance of this complication appears to be a sign of poor prognosis. PMID- 1754104 TI - Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis. AB - Anti-neutrophil cytoplasmic antibodies (ANCA) have been identified as a diagnostic marker in primary systemic vasculitis, and immunofluorescence assays identify two patterns of binding: cytoplasmic (C-ANCA and perinuclear (P-ANCA). We have examined retrospectively the use of such assays in long-term monitoring of disease activity, in order to determine the relationship between presence of ANCA and relapse, and to assess their suitability as a guide to therapy. Seventy patients were studied over a period of 50 months, using clinical and laboratory criteria for the diagnosis of relapse and the internationally standardised immunofluorescence assay for detection of ANCA. In 19 patients C- or P-ANCA were detectable throughout the study period; six of these (with C-ANCA) relapsed. In 18 patients ANCA were undetectable during long-term follow-up; none of these patients relapsed. In 33 patients C- or P-ANCA were intermittently present; nine of these relapsed and all had C-ANCA detectable at the time of relapse. In six of the nine cases, relapse was accompanied or closely preceded by reappearance of C ANCA. We conclude that continuing presence and reappearance of ANCA may identify patients who are at risk of relapse and who are most likely to benefit from long term immunosuppressive therapy. PMID- 1754105 TI - Heterogeneity of glutathione S-transferase isoenzyme expression in renal disease. AB - Recent work has suggested that glutathione S-transferase (GST) enzymuria may be used to assess renal injury in transplant kidneys. There is little work investigating the possibility of using glutathione S-transferase enzymuria to assess other renal diseases and this study was undertaken to evaluate the localisation of GST isoenzymes in various glomerular and tubular pathologies so that the specificity of these enzymes as markers of tubular injury could be defined. Immunostaining was carried out to establish the location of alpha and pi class GST in renal biopsies from patients with a wide variety of renal diseases including membranous glomerulonephritis, minimal-lesion glomerulonephritis, mesangial proliferative glomerulonephritis, loin pain haematuria syndrome, and renal allograft rejection. In the cases of glomerulonephritis studied, alpha class GST was detected in proximal tubules and pi class GST in distal convoluted tubules, podocytes, and Bowman's capsule. The majority of cases of glomerulonephritis showed a heterogeneous pattern of expression of both isoenzymes: that is, there was variation in intensity of staining both in single tubules and also between tubules as opposed to the uniform staining pattern observed in normal kidneys. The location of enzymes in the cases of glomerulonephritis was the same as that in normal kidneys and we were unable to demonstrate any de novo expression of GST isoenzymes. However, seven out of ten renal allograft biopsies showed expression of pi class GST in proximal tubules which were atrophic. Provided there is no significant tubular atrophy, urinary release of these enzymes may be used to localise renal tubular injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754107 TI - Pharmacokinetics of recombinant human erythropoietin in children with renal failure. AB - The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEpo; 40 units/kg1) were investigated in children (9-16 years) with end-stage renal failure. After an intravenous (i.v.) dose, serum rHuEpo concentrations declined in a monoexponential manner with a mean half-life (t1/2) of 5.6 +/- 3 h (+/- SEM; n = 9). Serum clearance and the apparent volume of distribution were estimated to be 10.1 +/- 0.9 ml h-1 kg-1 and 79.5 +/- 5.0 ml kg-1 (n = 9) respectively. Subcutaneous (s.c.) delivery resulted in serum values that peaked at 10 h, and thereafter concentrations declined slowly with a t1/2 of 21.1 +/- 4.5 h (n = 9). Serum rHuEpo concentrations were maximal at 14 h after i.p. administration and the t1/2 was 9.5 +/- 1.0 h (n = 3). The mean fraction absorbed of SC rHuEpo was 0.40 whereas after i.p. administration this fraction was only 0.17. These results show that after both s.c. and i.p. delivery, disposition of the hormone is rate limited by absorption, and bioavailability for these extravascular routes is poor. In addition, comparison of the results with those available for adults indicates that rHuEpo is better absorbed but more rapidly cleared in children. PMID- 1754106 TI - Characterisation of the binding of low-density lipoproteins to cultured rat mesangial cells. AB - Mesangial cell lipid accumulation is a recognised feature of glomerular disease and has been implicated as a factor in the pathogenesis of renal injury. To investigate possible mechanisms of such accumulation, binding of 125I-labelled human low-density lipoprotein (LDL) to rat mesangial cells was studied in vitro. Experiments were performed at 4 degrees C to prevent ligand internalisation. LDL remained associated with the cells after repeated washing. Binding was time dependent, was inhibited by addition of an excess of unlabelled LDL, but to a much lesser extent by apoprotein-A-rich high-density lipoprotein particles devoid of apoprotein E (HDL-A). Specific binding reached saturation at an LDL concentration of 21 micrograms/ml, required the presence of calcium, and was inhibited by heparin and dextran sulphate. Scatchard analysis suggested a single class of binding site (Kd 22.7 micrograms protein/ml). Higher binding affinities were obtained when rat LDL was substituted for human LDL (Kd 1.3 micrograms/ml) and when human fibroblasts were exposed to human LDL under identical experimental conditions (Kd 3.0 micrograms/ml). Further experiments at 37 degrees C demonstrated degradation of LDL by cells. These results suggest that mesangial cells possess apoprotein B, E receptors. Mesangial cell lipid accumulation may therefore result from receptor-mediated endocytosis of LDL particles. PMID- 1754108 TI - Multicentric study on paired filtration dialysis as a short, highly efficient dialysis technique. AB - Paired filtration dialysis (two-chamber haemodiafiltration) was evaluated as a short, highly efficient renal replacement therapy in 35 uraemic subjects belonging to three different dialysis centres. The study period was 1 year. Patients were divided into two groups according to their body-weight and drinking habits. The smaller patients underwent 150-min dialysis sessions three times weekly. The larger patients underwent 3-h treatments thrice weekly. The treatment was adequate in all patients according to the KT/V criteria of adequacy. The intradialytic symptomatology was remarkably low and the treatments were well tolerated in all patients. The study confirms the reliability of paired filtration dialysis as a short dialysis technique. In some patients 150 min may be insufficient to achieve an adequate dialysis efficiency and 180 min may be required for the majority of the population. PMID- 1754109 TI - Post catheterisation vein stenosis in haemodialysis: comparative angiographic study of 50 subclavian and 50 internal jugular accesses. AB - From January 1986 to December 1990 we studied angiographically the subclavian brachiocephalic vein of 100 patients dialysed by subclavian catheter for 50 (first group) and by internal jugular catheter for the 50 others (second group). These two groups were not statistically different as regards age (61.6 +/- 11.3 years in the first and 61 +/- 11.1 in the second), sex (48% and 56% were women), duration of catheter insertion (31 +/- 21.8 and 31.7 +/- 16 days), and the number of dialysis sessions (13.5 +/- 9.1 and 13.6 +/- 7.1). The type of catheters, the frequency of removal for poor flow (16% in both groups) or infections (6% in both groups), and the local nursing were similar in the two groups. The only difference was the side of cannulation: the right side in 58% of cases in group 1 and 78% in group 2. The angiographic study revealed a stenosis of the vein in 42% of the subclavian group and in 10% of the internal jugular group: a dramatic difference in favour of the internal jugular route, whose superiority over the subclavian route is asserted in respect of venous access of dialysed patients. PMID- 1754110 TI - Experience with a new method for percutaneous renal biopsy. AB - Between January 1989 and August 1990 a new technique for percutaneous renal biopsy was evaluated in all patients undergoing native kidney biopsy in our hospital. The method combines the use of an automated biopsy device, disposable biopsy needles, and a needle guide attached to an ultrasound probe. This allows real-time ultrasound scanning throughout the procedure. All biopsies were performed by trainee nephrologists. The success of the technique was evaluated by analysis of histopathological data, and the complications of the procedure from case-notes and nursing records. During the study 192 biopsies were attempted, of which 188 (97.8%) were successful. For each biopsy a mean of 2.8 needle passes were required and 75% of these obtained cores of tissue. An average of 25 glomeruli (range 1-90) were seen per biopsy. Although microscopic haematuria was almost invariable, there were no episodes of frank haematuria and no blood transfusion or surgical intervention was required. The new method is simple, providing accurate localisation of the kidney coupled with direct visualisation of the biopsy, and results in a very high success rate. Intrarenal needle dwell time is kept to a minimum and there were only minor complications. This technique deserves more widespread use. PMID- 1754111 TI - Guyon's syndrome in a long-term haemodialysis patient. PMID- 1754113 TI - End-stage renal failure in Kartagener's syndrome. PMID- 1754112 TI - Visceral leishmaniasis: an unusual case of fever in a renal transplant recipient. PMID- 1754114 TI - False aneurysm of the thyrocervical trunk. PMID- 1754115 TI - On not getting stuck. PMID- 1754116 TI - Accreditation by NLN and AANA. PMID- 1754117 TI - Watchful eye needed for textbooks. PMID- 1754118 TI - AIDS: advocacy and activism. PMID- 1754119 TI - The sequence of curriculum change in gerontology. Faculty first. PMID- 1754120 TI - The nurse as advocate. Issues in LTC. AB - Patients and residents of nursing homes need advocates; otherwise they tend to fall through the cracks, says Mitty. What are the issues and the barricades to good and equitable care? PMID- 1754121 TI - Review of nursing literature. Evolution of gerontological education in nursing. AB - Gerontological nursing is a rapidly expanding component of nursing education, especially as our elderly population increases. Philipose, Tate, and Jacobs provide a useful assessment of the nursing literature on this topic. PMID- 1754122 TI - A national survey to identify evaluation criteria for programs of health care for homeless. AB - We know that programs to deliver health care to the homeless are springing up all over the nation, but are they effective? Hunter, Crosby, Ventura and Warkentin attempt to get a sense of what data is being collected. In doing so, they identify the difficulties in collecting data on this transient population. PMID- 1754123 TI - Hospice care for the living dead. PMID- 1754124 TI - Nurses who kill. PMID- 1754125 TI - A workable solution to test review. AB - The authors describe a test review procedure that provides immediate feedback for faculty and students. The review procedure is described and the benefits for students and faculty are discussed with specific examples. Methods for using information gained from the test review procedure are also suggested. PMID- 1754126 TI - Measuring affective factors in RN/BSN programs. AB - Assessment of affective outcomes is needed in nursing education. This study examined changes in professional attitudes in RN/BSN programs and the relationships between selected affective factors and professional attitudes. Implications for nursing education are identified relative to student advising/counseling and curriculum. PMID- 1754127 TI - A successful student experience with the well-elderly. PMID- 1754128 TI - Teaching strategies for critical thinking. AB - Critical thinking is a phase that is being heard frequently in nursing education. Nurse educators are encouraged to teach students to think critically because of the higher-order thinking skills that are required in our complex health care delivery system. The challenge to educators is the selection, development, and implementation of appropriate teaching strategies. This article describes a variety of strategies for teaching critical thinking within the context of nursing. PMID- 1754129 TI - Evaluating students' esthetic knowing. AB - Few references in education are made to evaluating students' performance in the art of nursing (esthetic knowing). To address this rarity, a client-based clinical evaluation modality was developed using clients as the "critics" of students' esthetic knowing. The findings suggest that having clients evaluate students' esthetic knowing is an appropriate evaluation modality and is especially important as empirically based cirricula shift to include esthetics as a central element. PMID- 1754130 TI - Nurses in medical education. PMID- 1754131 TI - Copyright law and the nursing professor. AB - The copyright law affects the resources that are available to faculty for educating students. The author discusses the concept of fair use in academe, the process for obtaining permission to copy materials that have been copyrighted, and the rights of the professor who has created works during employment. An application of the copyright law to the publication of students' papers is presented. PMID- 1754132 TI - Who's the boss? Editor-author relationships. PMID- 1754133 TI - An innovative collaborative model for RN-BSN education--the whys and hows. PMID- 1754134 TI - The consumer role in nursing education. PMID- 1754136 TI - Do nursing students need AIDS education? PMID- 1754135 TI - Evaluation of an integrated curriculum: the Waltz Model. PMID- 1754137 TI - A clinical learning experience in discharge planning. PMID- 1754139 TI - The Southeastern Doctoral Forum. PMID- 1754138 TI - The Parent-Child Council. PMID- 1754140 TI - Cheating and plagiarism. PMID- 1754141 TI - Student conflict management: before and after instruction. PMID- 1754142 TI - Health fairs bring wellness concepts to life. AB - Incorporated into the nursing curriculum, the health fair is a stimulating, unique, nontraditional educational project that examines effective health education tools, leadership skills, and interaction with the community. Students test theories and collaborate with other school disciplines while planning, implementing, and evaluating health education and health fair promotion. Health fairs help students to identify positive lifestyles and create opportunities to test the skills needed to improve the population's wellness level. PMID- 1754143 TI - Complementary therapies in nursing. PMID- 1754144 TI - Complementary health. PMID- 1754145 TI - Let me rub it better. PMID- 1754146 TI - Rising to the challenge. PMID- 1754147 TI - Preventing surgical wound infection. PMID- 1754149 TI - A chance for unity. PMID- 1754148 TI - Learning at Liverpool. PMID- 1754150 TI - Keeping the workers happy. PMID- 1754151 TI - Where is thy sting? PMID- 1754152 TI - The alternative approach. PMID- 1754153 TI - Imaging inflammation with radiolabelled white cells: 99Tcm-HMPAO or 111In? PMID- 1754154 TI - Semi-quantitative analysis of SPECT with the iodinated fatty acid 15-(ortho-123I phenyl)-pentadecanoic acid. AB - 15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA) in contrast to the para-isomer pPPA has a prolonged retention in the normal human myocardium. Following qualitative evaluation, a semi-quantitative analysis of oPPA-SPECT is presented in 52 patients (41 with coronary artery disease (CAD) and 11 normals). Data were compared to the results of coronary angiography (CAD patients). Up to 220 MBq 123I-labelled oPPA were injected intravenously after overnight fasting and bicycle exercise. Four minutes later SPECT acquisition (180 degrees technique) was started. In 15 patients a second dose of oPPA was injected 2.5 h later and the study was repeated under rest conditions. Compared to our qualitative analysis the semi-quantitative approach revealed a lower sensitivity of 76% for the detection of CAD (global, stenoses greater than 50%) (specificity was not analysed because the normal patients served as the control group for the calculation of normal values). Because the sensitivity does not exceed that of 201Tl-SPECT or MIBI-SPECT, oPPA is not recommended for the detection of CAD, but it may serve for the evaluation of myocardial viability in ischaemic regions. PMID- 1754155 TI - Comparison of 99Tcm-HMPAO-labelled white blood cells and 67Ga citrate scans to detect myocarditis in the acute phase of Kawasaki disease. AB - Myocardial imaging with 99Tcm-HMPAO-labelled white blood cells (WBC) and 67Ga citrate was used to detect myocarditis in the acute phase of Kawasaki disease among 22 infants and children; 18 cases of myocarditis were detected by 99Tcm HMPAO-labelled WBC heart scans, but only one case was detected by 67Ga citrate heart scans. In conclusion, 99Tcm-HMPAO-labelled WBC scanning provides a more sensitive method than 67Ga citrate scanning in the detection of myocarditis in Kawasaki disease. PMID- 1754156 TI - Changes in arterial oxygen saturation during isotope perfusion scans using human macroaggregates of albumin. AB - Sixty-three patients undergoing isotope ventilation/perfusion scintigraphy for suspected pulmonary embolism were monitored using pulse oximetry. Xenon inhalation had no adverse effect on arterial oxygen saturation. Fifty-seven per cent of patients demonstrated a drop in oxygen saturation of 2-10% within 5 min of injection of macroaggregates. Small changes in arterial oxygen saturation reflect larger changes in the arteriole partial pressure of oxygen. In 10 patients, oxygen saturation dropped to 91% and below, corresponding to an arterial pO2 of less than 60 mm Hg. The effect lasted up to 30 min and is thought unlikely to be simply due to arteriolar blockade. Falls in arterial oxygen saturation cannot be correlated with any specific pulmonary pathology and appear unlikely to be of any clinical significance in most patients. PMID- 1754157 TI - The effect of minor gastric surgery on gastric emptying in the rat. AB - A new minimally invasive technique has recently been described which enables gastric emptying to be assessed on repeated occasions without the need for animal sacrifice. This technique has been applied to study the effect of a laparotomy or gastrotomy on gastric emptying in the rat. Groups of 10 animals underwent either a laparotomy or a gastrotomy, or were unoperated controls. Solid and liquid gastric emptying studies were performed preoperatively, and for two postoperative months. Emptying was unchanged in unoperated controls. Laparotomy animals showed delayed emptying of both solids and liquids, returning to normal by two months. Gastrotomy animals showed a similar delay in solid emptying, but liquid emptying was within the normal range postoperatively. It is concluded that minor abdominal surgery causes marked alteration in gastric emptying. The comparable emptying delay for patients is unknown, but this should be considered when patients are recovering from operation, and when interpreting postoperative gastric emptying studies. PMID- 1754158 TI - Hepato-splenic distribution of 99Tcm-phytate and hepato-enteric distribution of 99Tcm-DISIDA in mice with carbon tetrachloride-induced acute liver damage. AB - The hepato-enteric distribution of 99Tcm-labelled DISIDA and the hepato-splenic distribution of 99Tcm-labelled phytate were studied in controls and in mice with carbon tetrachloride-induced acute liver damage. The test group animals showed a diminished excretion of DISIDA to intestine with retention of this tracer in the liver and an increased splenic uptake of phytate. No changes in the hepatic uptake of phytate were found. The joint evaluation of both tracers in the study of diffuse liver disease is discussed. PMID- 1754159 TI - Chemotherapy for retinoblastoma: where do we go from here? A review of published literature and meeting abstracts, including discussions during the Vth International Symposium on Retinoblastoma, October 1990. AB - The history of the application of chemotherapy in the management of retinoblastoma (RB) may conveniently be divided into three eras: initial enthusiasm (from early 1950s to mid 1970s), realism (from late 1970s to mid 1980s) and possibility (from mid 1980s to the future). Available data from each of these eras are reviewed in the clinical categories of: intraocular RB, micrometastatic RB and overt dissemination. The latter is further sub-classified into: orbital invasion, central nervous system involvement and systemic metastases. Experimental models are described with particular emphasis on future directions. Early reports led to initial optimism subsequently dampened by a more critical approach. Recent results with increasingly effective chemotherapeutic regimens offer the possibility of a valid contribution in each of the above clinical settings. A multi-modality approach is recommended optimizing a combination of the most active drugs with continuing refinements of other techniques. In selected patients with intraocular, and particularly bilateral RB, visual outcome may be enhanced by the combined use of non-surgical modalities. Adjuvant treatment of presumed micrometastases needs to be studied within risk categories defined by prognostic factors. Invasion of the ocular coats and/or of the optic nerve are the most relevant factors but there are continued difficulties in defining the extent of involvement and eligibility criteria for such a strategy. Overt dissemination has recently been demonstrated to be curable in each of the three subgroups above. Intensive regimens incorporating cyclophosphamide, vincristine, cisplatinum, etoposide and possibly doxorubicin, plus intrathecal agents in combination with radiation therapy and, in some instances supplemented by bone marrow transplantation have produced promising results. Multi-institutional collaboration has been encouraged by the recently formed International Committee for the Staging and Management of Retinoblastoma, opening the way for prospective clinical trials. At the same time both laboratory and clinical experimental studies are being pursued and may produce further improvements in currently available strategies. PMID- 1754160 TI - Retinoma. Case studies. AB - The new concept of retinoma, or retinocytoma, brings up the rare 'spontaneous regressions' long-reported in the literature. Systematic investigation of all relatives of children suffering from retinoblastoma is showing up more and more retinoma cases undetected until now. From 1975 to 1990 the authors have identified 11 retinoma cases amongst 103 retinoblastoma patients and their families. The average age of the retinoma patients is 23 years with a mean follow up of four years. There are four bilateral cases, one of which with phthisis bulbi, three unilateral retinomas associated with retinoblastoma of the fellow enucleated eye, and four unilateral cases. Of the 11 retinomas, seven patients have a family history of retinoblastoma. Of the seven patients of procreating age, 16 offspring, three abortions and two miscarriages are noted. Of the 16 offspring, 12 developed retinoblastoma, 11 of which bilaterally. One 21-year-old patient presented in the process of malignant transformation. A child, enucleated for retinoblastoma of one eye and showing lesions conforming to retinoma in the fellow eye at two years of age, suffered an osteosarcoma when nine years old. The authors' data show that retinoblastoma and retinoma follow the same genetic changes and consequently require the same investigation and follow-up. This study indicates a frequency of retinoma of 10% amongst retinoblastoma patients and their families which is higher than that usually quoted. PMID- 1754161 TI - Incidence of retinoblastoma in Nagasaki Prefecture, Japan. AB - From 1965 to 1986, thirty-four patients with retinoblastoma were born in Nagasaki Prefecture, Japan, 23 with unilateral and 11 with bilateral retinoblastoma. The incidence of retinoblastoma was calculated to be approximately 1 in 16,053 births; it was bilateral in 1 in 49,618 births. There was no significant difference in the incidence of retinoblastoma between urban and rural areas. In Shimabara district it was 1 in 10,331 births--much higher than in any other district of Nagasaki Prefecture. Historically, almost all the natives had been killed in the Shimabara War in 1637, and then people immigrated to Shimabara mainly from Hyogo, Aichi and Shizuoka Prefectures. The authors compared the incidence and distribution of retinoblastoma in these three prefectures with the figures in Shimabara. The incidence in the Tamba and Tajima districts of Hyogo Prefecture was 1 in 10,570 and 1 in 10,411, respectively, very similar to that in Shimabara. The authors wonder if this similarity is only an accidental coincidence when the historical relationship among the three districts is considered. PMID- 1754162 TI - Second non-ocular tumours in survivors of bilateral retinoblastoma. A 30-year follow-up. AB - The authors have reviewed a series of 80 patients treated at the Curie Institute before 1965 for bilateral retinoblastoma. They present their cases of second non ocular tumours in these patients and discuss their results and the possible factors influencing the percentage of second tumours in these patients. PMID- 1754163 TI - A hereditary syndrome with retinopathy and ataxia or deafness in two consanguineous brothers. AB - Of two brothers born of Sephardic first cousin parents one presented with congenital neural deafness, nyctalopia, visual field loss, flat ERG, unintelligible speech and a shuffling gait, and the other with severe ataxia, severe decreased visual acuity, mild field loss, decreased ERG, dysarthric speech and high grade myopia. The diagnosis of Usher syndrome type 1 or 2 is discussed as well as the possibility that both brothers have different genetic disorders. PMID- 1754164 TI - X-linked megalocornea. Ocular findings and linkage analysis. AB - A family with X-linked megalocornea (XMC) is presented. The most typical ocular features of the disease (cornea globosa, arcus lipoides, mosaic dystrophy of the cornea, pigment dispersion, and cataract) are described and their diagnostic value is discussed by reviewing the literature. Linkage data suggest that the XMC locus maps in the region Xq13-q25, most probably in Xq21-q22. PMID- 1754165 TI - [Comparative analysis of the results of the treatment of pain after amputation of the arm]. AB - Postamputation pain syndrome significantly embarrasses prosthetics. In the article is described the transposition of the nerve trunks of the brachial plexus with terminal neuromas into the formed tunnel under the musculus pectoralis major, applied by the authors at 47 invalids (52 operations) with pain in the arm stump. The results of an operation have been studied in comparison with the results obtained after resection of the terminal neuromas. The data allow to recommend the translocations of the nerve trunks with the terminal neuromas in case of the pain syndrome after an arm amputation as more effective ones. PMID- 1754166 TI - [Surgical treatment of habitual dislocation of the shoulder]. AB - In the article is presented the analysis of treatment of 32 patients with shoulder joint instability. There have been studied the outcomes of treatment after the arm "suspension" operations, interventions at the anterior region of an articulation, derotational osteotomies of an arm. There have been considered the problems of etiopathogenesis of shoulder joint instability. There have been analyzed the peculiarities of the tactical approach to the treatment of patients with shoulder joint instability. There is presented the principled position of the authors' approach to the selection of pathogenetically substantiated method of the habitual shoulder slip operative treatment. PMID- 1754167 TI - [Surgical treatment of anterior instability of the shoulder joint]. AB - In the article are presented data on the operative treatment of 52 patients (54 operations) with anterior instability of the arm joints. Patients have been distributed into 4 groups depending upon the character of intra-articular damages, revealed in the process of arthrotomy. Each group of patients was subjected to adequate operative intervention, based upon Bankart's method. The authors proceeded from the principle that the arm joint instability treatment should be aimed at removal of intra-articular damages. There have been restored integrity of the damaged cartilage cushion and the joint capsule, the capsule plasty and blocking of the anteroinferior joint sinus. The treatment tactics of the kind allowed to achieve the maximum stability of the arm joint and prevent postoperative recurrencies. Long-term results have been studied with 41 patient, no recurrencies have been noted. The operated limb function has been restored with the majority of the patients. PMID- 1754168 TI - [Osteosynthesis in hand bone fractures in children]. AB - At 12 preparations of the upper extremities of still-born fetuses has been studied microcirculatory channel of long bones of a hand. Clinical confirmation of the experimental results is based on the analysis of data obtained in process of treatment of 54 children with instable fractures of phalanges and metacarpal bones. An arterial channel of long bones of a hand is formed by the branches of finger arteries and vessels of the surrounding tissues. Epiphysis, metaphysis and growth cartilage have common circulatory system. The types of phalanx epiphysiolysis determine the terms of the open reposition realization. Comparison of morphological data and clinical observations demonstrated that the optimal methods of fixation of instable fractures of long bones of a hand are as follows: diafixation by means of wires, intramedullary osteosynthesis and perosseous compressive-distractive osteosynthesis. PMID- 1754169 TI - [Areas of safe use of bone nails on the forearm]. AB - On the basis of the data of topography-anatomical study, carried out at 30 upper extremities, are proposed zones and directions of safe application of wires of the compression-distraction apparatus at 4 forearm levels, developed with allowance made for individual differences in structure and topography of vessels and nerves as well as functional position of the segment. An experimental examination (30 extremities) and clinical approval (30 patients) of the proposed zones and directions have confirmed the practical use of the obtained data that allows to recommend them to be widely introduced into the clinical practice. PMID- 1754170 TI - [Roentgeno-densito-planimetric evaluation of the bones after correction of the defect]. AB - In an experiment with 52 dogs (2 experimental series) there were studied, by means of a roentgeno-densito-planimetric method, changes of bone substance in the process of the upper half of tibia defect compensation with the aid of transplant, displaced within the defect, and distraction regenerate, formed therewith. The data obtained indicated that formation and mineralization of new bone substance have been accompanied by intensification of the transplanted bone osteoporosis. Osteoporosis manifestation has been determined by an amount of newly formed bone substance and increased with the increase of the distraction regenerate size. Osteoporosis manifestation decreased with application of large bone transplant that allows to preserve in greater degree the transplanted bone strength in the process of restructuring. PMID- 1754171 TI - [Biochemical and anatomic changes in the muscles after leg bone lengthening by the Ilizarov method]. AB - In process of crus lengthening, following the method, given by Ilizarov G. A., with 22 adult patients have been studied the peculiarities of metabolic processes of muscle tissue of the lengthened segment as well as the muscle tissue structural changes. As the tests were used; determination of lactate dehydrogenase content and its isoenzymatic spectrum in the blood serum, the residual products of lactic and pyruvic acids glycolysis, relating to the higher indications of the internal medium of an organism; carboxylase activity detection. Energy provision of an organism was estimated according to the ATP content; anatomical state of muscles of the lengthened extremity segment and muscle tissue structure were estimated by means of contrast myography. Dynamics of biochemical indexes suggests that the sparing character of an operation, patient mobility from the first days, preservation of locomotive and supporting function contribute to prevention of metabolic disease and ensure earlier transformation of catabolic reaction to anabolic one. Carboxylase and lactate dehydrogenase activity increase indicates the biochemical adaptation of an organism. Metabolic changes well correlate with the detected structural changes in the lengthened crus muscles. PMID- 1754172 TI - [Characteristics of regional hemodynamics in the lower extremities of patients with flaccid paralysis]. AB - On the basis of treatment and examination of 2675 patients with residual effects of poliomyelitis and consequences of the nervous system traumata are considered the functioning peculiarities of vascular system of the lower extremities in case of absence or abrupt decrease of pumping function of the skeletal muscles. There have been detected discrepancies between the reovasographic regional blood circulation pattern and the microcirculation state indexes in the tissues of the damaged extremity. They have studied the dynamics of the hemodynamics indexes in the process of preoperative preparation, during early and late postoperative periods as well as during remote postoperative periods. There is suggested the idea of correlation of the regional hemodynamics with the extremity supporting state. PMID- 1754173 TI - [Diagnosis of fractures by sound]. AB - For the purpose of objective evaluation of the sound diagnosis the authors have generalized an experience of application of four methods of the acoustic diagnosis of bone fractures. There have been compared the efficiency of the auscultatory percussion method, the method of its objectivization by means of measuring devices, the sound diagnosis method, following the pattern of auscultatory percussion and self-sustained oscillation measuring method. There have been noted the high efficiency and up to 98% coincidences with clinico roentgenologic data in case of application of the sound diagnosis method with the self-sustained oscillation systems. PMID- 1754174 TI - [Single-stage total removal of the cervical vertebrae in plasmacytoma]. AB - The article includes the description of successful case of surgical treatment of a patient (53 years old) with VC plasmocytoma, complicated with upper paraparesis, tetanoid paraplegia and pelvic disturbances. The patient has been subjected to complete removal of VC in one stage of 2 accesses. The patient's spine has been fixed by means of implant, made of corundum porous ceramic, metal plate and lavsan band. A year after the operation--no tumor recurrence, the patient walks without additional support. In the process of discussion of the given observation the authors suggest that the technical difficulties of the operation are quite surmountable and its expediency is obvious. PMID- 1754175 TI - [Allogeneic arthrodesis of the distal interphalangeal joint of the fingers]. PMID- 1754176 TI - [Biomechanical study of the fixation stability in rupture of the pubic symphysis]. PMID- 1754177 TI - [Treatment of pseudarthroses and defects of the forearm bones after gunshot wounds]. PMID- 1754178 TI - [Orthotic devices in the treatment of injuries of the ankle joint]. AB - For immobilization of foot-crus segment in case of damages of talocrural articulation region is proposed a short orthese, made of polyvic. Elastic properties of the material at convergence of the orthese walls allow to develop the compressive force in the region of distal tibiofibular syndesmosis up to 90 N. Immobilization reliability was judged by tensometry. An orthese allows to set the foot subluxation, make reposition of the malleolus fragments. In case of fracture of the lower third of fibula an appliance with concave control pelot, made on the basis of an orthese, is used. The treatment methods foresee the most complete utilization of extremity functions even during the early post-traumatic periods. An orthese and an appliance with positive results were used by 69 patients with the talocrural articulation damages. PMID- 1754179 TI - [A case of congenital hypodactyly of the hand and foot]. PMID- 1754180 TI - [Lengthening of finger stumps using the apparatus for external fixation]. PMID- 1754181 TI - [A method of the treatment of equinus deformity]. PMID- 1754182 TI - [Femoral fracture at the site of a dystrophic cyst]. PMID- 1754183 TI - [Treatment of transcondylar fractures of the humerus in children by continuous skeletal traction]. PMID- 1754184 TI - [Training of students in orthopedics and traumatology in medical schools and physicians-orthopedists and traumatologists at the GIDUV (the National Institute for Continuing Education of Physicians]. PMID- 1754185 TI - [Protective titanium nitride coating of fixation devices for osteosynthesis]. PMID- 1754186 TI - [A device for preliminary reposition and fixation of crural bones]. PMID- 1754187 TI - [An extractor for removal of broken hollow nails after intramedullary osteosynthesis]. PMID- 1754188 TI - [An attachment for orthopedic table used in skeletal traction]. PMID- 1754189 TI - [Problem of skin expansion in the orthopedic and traumatological practice]. PMID- 1754190 TI - [An apparatus for thr restoration of hand movements]. PMID- 1754191 TI - [Treatment of flat anterior segment of the foot in women]. PMID- 1754192 TI - [Electric stimulation of the muscles using the CHENS-2M apparatus in spinal osteochondrosis]. AB - The authors of the article established that the application of electrostimulation by means of the apparatus CHENS--2M allows to remove the pain syndrome and to improve the amplitude of motion in the spine. The reovasography examination data confirm the efficiency of the applied treatment. The proposed method of treatment of the spine osteochondrosis should be recommended for practice due to its simplicity and accessibility. PMID- 1754193 TI - [Use of a transplant from the iliac crest with axial blood supply for anterior spondylodesis of the lower lumbar and lumbosacral segments of the spine]. AB - The method of anterior osseoplasic stabilization of inferiolumbar and lumbosacral parts of spine by means of non-free vascularized transplant from the anterior part of the iliac crest has been developed. In the anatomical experiment at 100 objects there have been studied alternative surgical anatomy of vascular transplant pedicle from deep vessels, surrounding the iliac bone, ascertained the possibility of its lengthening at the cost of the muscular-periosteal "cuff". 9 patients have been operated on with positive results. There have been achieved an acceleration of the osseous stabilization of the spine by 1.5-2 times as compared with the traditional methods without essential restructuring of resolution of transplants with vascular connections. PMID- 1754194 TI - [Possibilities of reducing the duration of the treatment of patients with tuberculous spondylitis]. AB - In the article are described the results of operative treatment of 185 patients with tuberculous spondylitis. In order to restore stability there was carried out posterior spondylidesis after Genle with removal o ffoci by means of posterior access in 70 patients. 115 patients were subjected to anterolateral spondylidesis, 55 of them--by generally accepted method and 60--with creation of trapezoid lock between the body of a vertebra and transplants. In this group of patients was used removable jacket made of polivike before the patient's elevation. In this case the term of the stationary treatment of the III group patients was reduced by 2 times as compared with the I group and by 22--I day as compared with the 2 group. Long-term results were studied from 6 months to 7 years. In the first group there were excellent results in 67%, good in 20% and bad in 13% of cases. In the patients of the 2 and 3 group there were excellent results in 96%, good in 3.4% and bad in 0.6% of cases, when there was observed resolution of transplant with 1 patient of the 2 group. PMID- 1754195 TI - [Use of dalargin in the complex treatment of complicated injuries of the thoraco lumbar segments of the spine]. AB - In the present report there has been pursued an object of studying the efficiency of the preparation dalargine (synthetic preparation, analogous to encephaline) in case of unstable spine and spinal cord injuries. Under the observation there were 32 operated patients. Dalargine was administered endolumbally by 2 mg, dissolved in 2 ml of physiologic salt solution. The results were evaluated by several categories: locomotive function, sensitivity, pelvic organ function, pain, spasticity, trophic disturbances. PMID- 1754196 TI - [Breaking of distractors of the Harrington type after surgical treatment of scoliosis]. AB - 180 patients with scoliosis (aged 12-29 years) were subjected to the correction of deformation by means of the Harringtone type distractors and spondylodesis with utilization of osseous transplants. In 24 of them (13,3%) the distractor has been broken in different terms after the operation. The danger of the break increases with the age of the patients and abruptly increases in case of scoliosis of the V degree (in excess of 90 degrees) and in case of necessity to bend the distractor to correct the kyphoscoliosis. The distractor break is associated not with the material structure but with the rod design. PMID- 1754197 TI - [Surgical treatment of scoliosis using a controlled dynamic device]. AB - The article reports about the development of the original implanted device, ensuring externally controlled dynamic correction of scoliosis. The construction has been utilized with 6 patients with scoliosis of the IV degree. In 5 cases after operation was achieved the spine distraction of 10-37 mm. As the result, there was obtained an additional correction of the correcting arch from 6 degrees to 17 degrees as compared with achieved in the process of the operation. PMID- 1754198 TI - [Effectiveness of acupuncture analgesia in the treatment of chronic post traumatic pain syndromes]. AB - The present work is dedicated to the study of the acupuncture analgesia efficiency in ambulatory practice in treatment of chronic post-traumatic pain syndrome as well as the comparative characteristics of the acupuncture analgesia and electric analgesia in treatment of this pathology. There have been analyzed the results of treatment of the pain syndrome after the traumata of the lower limbs by the IRT method (106 patients), compared the terms and the results of the treatment by the above mentioned methods as well as by the separate acupuncture analgesia and electro-analgesia methods. As a result, it should be noted that the IRT method is more effective in treatment of the chronic pain syndrome as compared with the common traditional methods. The electroanalgesia method, in turn, contributes to more rapid pain soothing and restoration of the vegetative and trophic functions than acupuncture. PMID- 1754199 TI - [Oxygen therapy of gonarthrosis deformans]. AB - In the article is presented the comparative estimate of the oxygen therapy methods in treatment of the deforming gonarthrosis. The new method of treatment is described, including 4-5 courses of hyperbaric oxygenation therapy at 1-1.5 atms during 50 min and intraarticular introduction of oxygen. 3 groups of patients have been singled out. The proposed method have been applied with 32 patients. It turned out to be more effective and the course of treatment shorter as compared with the known methods: with application of hyperbaric oxygenation without local introduction of oxygen and localized introduction of oxygen in the joint without application of hyperbaric oxygenation. PMID- 1754200 TI - [Therapeutic approach in degenerative-dystrophic diseases of the hip joint in relation to the immunologic status]. AB - In the process of study of the immunological status peculiarities of 202 patients with some degenerative-dystrophic diseases of hip joint has been revealed that the hyperimmune reactions to tissular antigens of the joint components (bone, cartilage, synovial membrane) are more often observed in case of non-specific arthritis, asephic necrosis of the head of the femur and dysplastic coxarthrosis. These were precisely the states with more frequent postoperative complications, provoking the process development, joint ankylosing or formation of ossificates. Preoperative immunocorrection therapy of 20 patients by means of a course of low dose injections of plasma substitutes (polyglukine, hemodesis or reopolyglukine), individually selected by RIML and lymphocytotoxic test, allowed to arrest the lryperimmune manifestations. After reconstructive-restorative operations there was observed positive clinical and roentgenologic dynamics in the operated joint of the patients. PMID- 1754201 TI - [Value of electromyographic examinations in the diagnosis, treatment and rehabilitation of patients with complicated trauma of the spine]. AB - In the article are presented the results of clinico-electromyographic examination of 57 patients with complicated damages of lumbar part of the spine during acute, early, interim and late periods of treatment. During the acute period of the spine damage are singled out 3 types of manifestation of total spontaneous and induced (N-reflex, M-wave) bioelectrical activity, demonstrated the possibility of their application for prognostication of the operative and restorative treatment results. PMID- 1754202 TI - [Biomechanical data regarding the socket-neck orientation of hip endoprosthesis]. AB - On the basis of clinico-statistical, roentgenologic, morphological and spectral studies it is possible to draw the conclusion that the cause of the structural deformation of the bone tissue around the endoprosthesis parts and an approach of their instability is in the mechanical interaction of bone and explant. Under the influence of the biomechanical forces the socket of the endoprosthesis gradually changes its position from 45-90 degrees to 25-30 degrees. The original 25-30 degree positioning of the socket significantly decreases the moment of forces that it is subjected to and, as a rule, there is no socket displacement observed. That is why this socket positioning in the process of operation is a preferable one. But the angles of necks of the Sivash endoprosthesis and its modifications are equal to 130 degrees +/- 3 degrees and when the socket is positioned at an angle 25-30 degrees there can occur limitation of the limb abduction, the socket loosening, the structure fretting and metallosis of tissues due to the setting of the neck against the end of the insert. It is expedient to change the angle of the endoprosthesis neck to 150 degrees +/- 3 degrees and some shortening of the neck. PMID- 1754203 TI - [Corrective osteotomy of the femur in the treatment of the syndromes of dysplastic instability of the hip joint]. AB - On the basis of analysis of short-term outcomes (1-5 years) of treatment of 139 patients (150 joints) with congenital dislocation and oluzation of the thigh, conclusion has been drawn that the application of corrective femur osteotomy with these patients should be limited with the cases of formation of pathology loading of the joint under conditions of negative intercomponental trophism. Restoration of correct anatomical interrelations between the components of the joint can be accompanied by the clinical decompensation of the hip joint state. Position of the cotyloid cavity and epiphysis of the head of the femur is of fundamental importance for further formation of the hip joint and its neck and diaphysis position is of minor importance. When positing indications for corrective femur osteotomy and its efficiency prognostication it is necessary to be orientated towards epidiaphysar and not cervicodiaphysar correlations. Removal of antetorsion of the head of the femur without due regard for the grade of its proximal epiphysis retroversion can lead to the development of external rotary contraction in hip joint. PMID- 1754204 TI - [Changes in the osteoarticular system after completion of the treatment of congenital hip dislocation in children and adolescents]. AB - There have been analyzed the results of the treatment of congenital femur dislocation in 189 children. It has been stated that the results of treatment are in direct relation with the timely commencement of treatment, dysplasia expression of pelvic and femur components, adequacy of the treatment methods to the pathology nature, observation of the orthopedics regimen and rehabilitation treatment. There have been detected the group of children, in which in spite of the treatment applied in total accordance with the rules of orthopedics, have been noticed the changes of the degenerative-dystrophic nature both on the side of dislocation and in the remote parts of skeleton. The obtained data are to be taken into consideration for vocational orientation of adolescents and at the stage of dispensary observation in order to compile the plans of rehabilitation treatment. PMID- 1754205 TI - [Various forms of lesions of the femur head in Legg-Perthes disease]. AB - The authors described small-focal, limited and disseminated forms of the femoral head affection. They differ in localization and extent of the necrotization foci and don't transform themselves in the course of disease. Comparison of anatomical data, roentgenologic and angiographic examinations allows to infer that the described forms of affection are conditioned by the blockade of the vascular basins of the intraosseous circulatory system of the epiphysis. It has been stated also that the disease duration, its outcomes are determined mainly by the femoral head affection form and a child's age. The high-risk groups have been singled out with consideration for the probability of formation of joint deformation and the conservative treatment. PMID- 1754206 TI - [Comparative evaluation of the results of conservative surgery for benign tumors and tumor-like bone lesions in children]. AB - The results of sparing operations of 576 children with benign tumors and tumor like bone affections have been analysed. There have been revealed the advantages of the complex method of treatment, envisaging the sparing approach to the damaged segment, thermal treatment of the residual osseous walls by means of CO2- laser and recipient-like plasty of the operational defect (UV--irradiated autologous bone marrow+allomaterial): absence of recurrencies, complete restoration of the bone structure in 9-12 months after the operation. PMID- 1754207 TI - [Treatment of femoral neck fractures]. PMID- 1754208 TI - [Treatment of patients with juvenile epiphysiolysis of the femur head using the Elizarov apparatus]. PMID- 1754209 TI - [Surgical treatment of tumors of the sacrum]. PMID- 1754210 TI - Measurement of vocal function. AB - Objective measurement of vocal function, e.g., acoustical analysis, is emerging as a necessity in clinical practice. Voice data assist in determining the diagnosis and prognosis of many voice disorder patients and provide documentation of the vocal quality before, during, and after treatment. PMID- 1754211 TI - Neuromuscular disorders of the larynx. AB - The voice may be affected adversely by a variety of neuromuscular disorders, including movement disorders, paralysis, and degenerative conditions of the central and peripheral nervous system. The diagnosis of these conditions usually requires high-technology tools, and the results of treatment are variable. Diagnostic considerations, aspects of a complete neurologic examination, an examination of the basic organization of neural control as it relates to the larynx, and treatment options are provided in this article. PMID- 1754212 TI - Laryngeal electromyography. AB - Laryngeal electromyography (EMG) is simultaneously a powerful clinical and investigative tool. EMG may be diagnostic and prognostic in cases of laryngeal or vagus nerve injury and can differentiate between vocal cord fixation and paralysis. EMG also is being used to help unravel complex laryngeal neural and muscle physiology. Basic principles of EMG, techniques of EMG limited to three muscles--the thyroarytenoid, the posterior cricoarytenoid, and the cricothyroid, and pitfalls of this procedure are discussed within this article. PMID- 1754213 TI - Functional voice disorders. AB - Functional voice disorders (FVDs) are common. The diagnostic criteria for six types of FVD and the results of treatment in a large series of patients are reported. Voice therapy was effective in 69% of the patients. Failure of voice therapy usually correlated with continued tobacco use, noncompliance with therapy, or premature termination of therapy. PMID- 1754214 TI - Voice therapy. Techniques and applications. AB - Voice therapy is the cornerstone of treatment for patients with voice disorders. The therapeutic role of the speech pathologist is important in patients with functional and organic voice disorders. Voice rest and various other treatment options, techniques, and applications for voices disorders are examined in this article. PMID- 1754215 TI - Care of the professional voice. AB - Care of the professional voice user, particularly the professional singer, requires that the otolaryngologist acquire special training. This group of patients demands gentle and appropriate treatment, rarely surgery, for a wide range of conditions that may affect vocal performance. PMID- 1754216 TI - Pediatric voice disorders. AB - Voice disorders are common among children, estimated to range from 6% to 23% in school-aged children. The various causes of voice disorders are presented in this article in addition to a discussion of normal laryngeal voice and development. Also presented are the causes of abnormal voice and brief discussion of a framework for multidisciplinary assessment and treatment of pediatric voice disorder. PMID- 1754217 TI - Vocal cord injection techniques. AB - Injection techniques for the rehabilitation of paralytic dysphonia (e.g., Teflon) remain popular in the United States. This article presents a historical perspective of vocal cord paralysis, its work-up, and the indication, timing, techniques, and results of vocal cord injection. PMID- 1754218 TI - Laryngoplastic phonosurgery. AB - Laryngoplastic phonosurgery is a new term used to describe all forms of laryngeal framework surgery to improve the voice. One of the most important new surgical techniques is medialization laryngoplasty (ML) for the correction of unilateral vocal cord paralysis. This article focuses on ML techniques, results, complications and indications; the artenoid adduction procedure (AA) is described as a complementary technique. In addition, some of the more experimental laryngoplastic procedures are reviewed. PMID- 1754219 TI - Surgery for benign lesions of the glottis. AB - This article examines benign lesions of the glottis and adjacent structures commonly encountered in clinical practice. The goals of management are to understand the cause and the characteristics of these lesions and to provide the most conservative management possible. Nonsurgical management is selected, if possible, with surgical intervention reserved for refractory conditions. Traditional cold steel operative techniques as well as carbon dioxide laser techniques are discussed in this article. PMID- 1754220 TI - Laryngopharyngeal manifestations of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) contributes to the development of many otolaryngologic symptoms and conditions, including chronic throat clearing, cough, sore throat, contact ulcer and granuloma, globus pharyngeus, cervical dysphagia, cancer of the larynx, subglottic stenosis, and cricoarytenoid arthritis. These conditions are discussed and the pathogenesis of GERD is also detailed. PMID- 1754221 TI - Restoring function to the injured larynx. AB - Laryngeal trauma often results in impaired laryngeal physiology, and may result in severe dysphonia. Effective rehabilitation requires the utilization of sophisticated diagnostic and surgical methods. PMID- 1754222 TI - Treatment options in spasmodic dysphonia. AB - Options in the treatment of spasmodic dysphonia include surgical interruption of the recurrent laryngeal nerve, anterior laryngoplasty, voice therapy, and Botulinum toxin injection. Although none of these treatments is ideal, Botulinum toxin injection appears to have the greatest potential to benefit the greatest number of patients. PMID- 1754223 TI - Nerve-muscle pedicle reinnervation of the paralyzed vocal cord. AB - Reinnervation offers great potential for the rehabilitation of the paralyzed larynx, a potential that has yet to be realized. The nerve-muscle pedicle (NMP) technique is one method of reinnervation that attempts to transfer a nerve with a portion of its muscle intact to a denervated muscle. The selection of the nerve to incorporate into a NMP is examined in the first part of this article. Experimental data that argue for and against the use of a NMP, a description of the indications and the techniques for the procedure, and a review of the clinical results are detailed. PMID- 1754224 TI - Electrical stimulation of laryngeal muscle. AB - Most functional electrical stimulation (FES) research has focused on the spinal cord-injured patient whose muscles are paralyzed but still maintain their innervation. This article details the investigation of FES of the laryngeal muscles. In time, FES may become a useful treatment for bilateral vocal cord paralysis (BVCP) and for some laryngeal movement disorders. PMID- 1754225 TI - Voice disorders. PMID- 1754226 TI - The spectrum of vocal dysfunction. AB - Levels of vocal use, types of vocal complaints, and the spectrum of vocal dysfunction are discussed in this article. Functional voice disorders account for 40% and organic conditions for 60% of patients presenting with voice disorders. Twelve percent of the patients are children. PMID- 1754227 TI - Approach to the patient with a voice disorder. AB - The author's approach to patients with voice disorders emphasizes the value of a multidisciplinary voice team, including an otolaryngologist, a speech pathologist, and a neurologist. PMID- 1754228 TI - [Ferritin (tumor marker) in patients with laryngeal cancer and precancerous conditions]. AB - Evaluation of the ferritin as a neoplasm marker was performed in laryngeal cancer patients. In 35 laryngeal cancer patients and in 21 laryngeal leucoplakia patients the ferritin serum level and the blastic transformation of leucocytes were tested. In both groups the high ferritin level was discovered. It is the sign of low specificity of ferritin as a neoplasm marker. There was no correlation between the ferritin serum level and the degree of the blastic changes of leucocytes. PMID- 1754229 TI - [Comparative studies of CT pictures and intraoperative findings in malignant neoplasms of the paranasal sinuses and nasopharynx]. AB - Five cases of malignant paranasal sinus and nasopharyngeal cancer were demonstrated. They illustrated the discrepancies in the evaluation of the extensive neoplastic process using CT scanning and intraoperative examination. The limitation of CT scanning in the diagnosis of advanced malignant cancer in this region was discussed. PMID- 1754230 TI - [Non-epithelial malignant neoplasms of the larynx]. AB - Among total number of 1399 patients with laryngeal malignant tumors treated in Cracow Otolaryngological Clinic in the years 1966-1985 there were only six (4%) patients with non-epithelial neoplasms. These patients were operated upon by various types of laryngectomy. PMID- 1754231 TI - [Remarks on creating skin flaps in so-called closed two-step tympanoplasty]. AB - The most often used skin-flap techniques in one-step and two-steps closed tympanoplasties are discussed. The correct plastic surgery of the meatal skin gave good results. In the ENT Clinic of the Medical Academy in Lodz techniques most often used are two-flaps tympanoplasties with anterior and posterior pedunculated flaps or tympanoplasties with a single pedunculated flap. PMID- 1754232 TI - [Value of adenectomy in the treatment of recurrent respiratory tract infections, sinusitis and otitis media in children]. AB - Two groups of the upper respiratory tract, sinuses and middle ear recurrent infections were analysed. The first one of 205 children has had the adenotomy, the second of 107 has not. In the surgery group the treatment results were statistically better. The indications and the contraindications to the adenotomy were discussed as well as the complications and postoperative care. PMID- 1754233 TI - [Hydrogel dressings in the otolaryngological practice]. AB - The authors described their own suggestions of advantages of the hydrogel bandages in ENT practice. The hydrogel is produced by Radiation Technique Institute of Polytechnique High School in Lodz. PMID- 1754234 TI - [100 years of modern tonsillectomy]. AB - The author has described a historic progress of tonsillectomy. He has also noticed that in present decade passes 100 years from the first execution of tonsillectomy (in today meaning of that intervention). Observing the development of the technics of tonsillectomy the author came to the conclusion that nowadays palate tonsils are removed in classical way ("dissection Method") or by "guillotine Method". PMID- 1754235 TI - [Evoked response audiometry in newborn infants examined earlier by fetal audiometry]. AB - The aim of this study was to investigate the influence of acoustic stimulus on behavioural heart responses of fetuses near term (38 to 42 weeks of gestational age) and comparison assessment of FHR to Auditory Brain Stem Responses (ABR) in the same babies after their birth. The study group consisted of 30 babies with pathological pregnancies and control group of 30 neonates of physiological pregnancies. Our results indicated, that the pattern of FHR accelerations after application of acoustic stimulus was significantly altered and depended on of the kind of pregnancy. Duration and amplitude of FHR obtained in the patients with complicated pregnancy were significantly smaller in comparison to the pattern observed in normal patients (142 msec to 249 msec, and 36 to 22 as well). Comparing the results obtained in FA (Fetal Audiometry) and ABR (Auditory Brain Stem Responses) we can say, that prolonged latency between a stimulus and accelerations is also combined with the prolonged latency of consecutive waves in ABR. Shortened duration of accelerations and its decreased amplitude could respond to the diminished amplitude in ABR recordings. PMID- 1754236 TI - [A case of recurrent inflammation of ear cartilage]. AB - The clinical course of the recurrent auricle cartilage inflammation was described. In Polish literature there were only 4 cases published. The etiopathogenesis, symptomatology and treatment were described. PMID- 1754237 TI - [Malherbe's calcifying epithelioma of the base of the nose in a child]. AB - The rare case of epithelioma calcifying of Malherbe of the nose of the 9 years old girl was presented. The tumor was operated whole. The follow-up proved good health without recurrencies. PMID- 1754238 TI - [Eosinophilic granuloma of the temporal bone]. AB - The authors describe current opinions about origin, pathology, histology, diagnosis and treatment of the eosinophilic granuloma. Clinical course, diagnosis and treatment of the own case were discussed. PMID- 1754239 TI - [A case of a child with congenital anomaly of the first branchial cleft]. AB - The authors of the article describe the case of a child surgically treated for inborn anomaly of the first branchial cleft. Basing upon this example, they discuss the difficulties that the surgeon may encounter during the operative treatment. Concluding, they present the characteristic features of this type of developmental anomaly. PMID- 1754240 TI - [A case of Warthin's tumor (papillary adenolymphoma) of the larynx]. PMID- 1754241 TI - [Extensive Stewart's tumor with an atypical way of spreading]. PMID- 1754242 TI - [Tracheo-arterial fistula as a complication of tracheotomy]. AB - The authors presented 2 cases of massive bleeding from brachiocephalic artery as a late complication after tracheotomy. In both deadly cases the artery wall was secondary damaged by the tracheal tube. The pathomechanism of this complication origin and significance of its acquaintance was discussed. PMID- 1754243 TI - [Use of ultrasonography in the diagnosis of laryngeal cancer]. PMID- 1754244 TI - Does the vestibulo-ocular reflex (VOR) merit redefinition? AB - The VOR has historically been described by parameters of the slow phase of nystagmus while fast phases have been systematically ignored. However, ample neurophysiologic and theoretical evidence suggests that fast phases are an integral part of the VOR and are not to be discarded in evaluation of vestibular function. In a series of experiments, normal subjects and compensated patients with total or partial loss of unilateral peripheral vestibular function were tested. They were exposed to sinusoidal oscillations (20 degrees, 60 degrees, and 120 degrees/second at 1/6 Hz and 25 degrees/second at 1 Hz) with no actual or imaginary visual targets (doing mental arithmetic) and the usual slow-phase parameters (gain, phase, etc.) were computed. The gaze (total eye position, slow and fast phase of nystagmus vs. head + head position in space) was also plotted vs. head position in space. It was found that in patients, fast phases of nystagmus are unequally (right vs. left) produced, extending the linear range of VOR function. It was also found that in normal subjects and patients, gaze essentially tracks the head in the absence of visual targets. It is concluded that fast phases of nystagmus contribute to gaze control during head rotations in darkness and that the definition and the testing of the VOR have to be modified to accommodate these observations. PMID- 1754245 TI - Mucociliary function following sinus mucosal regeneration. AB - To evaluate sinus mucosal regeneration and cilia motility after surgical removal, 15 rabbits underwent unilateral removal of maxillary sinus mucosa. The opposite sinus served as an unoperated control. After 10 weeks, specimens were taken for examination from all operated on and control sinuses. Light, dark-field, and electron microscopy were performed. Mucosa from eight of the 15 sinuses operated on showed ciliary regeneration by light microscopy; six of these exhibited motile cilia on dark-field examination. Histopathologic findings of marked fibrosis, decreased seromucinous glands, and significant inflammation were commonly present in the sinuses operated on. Electron microscopy revealed frequent abnormalities, including complex and edematous cilia and fewer than normal cilia per unit area compared to controls. The dark-field, light, and electron microscopic findings of the regenerated, post-surgical mucosa are discussed. PMID- 1754246 TI - Esophageal foreign bodies in adults. AB - The main point in managing suspected impaction of esophageal foreign bodies is to decide whether the patient needs an esophageal endoscopy. Decision-making is based on clinical history, physical examination, and radiographic studies. We review 100 cases of adults having esophagoscopy for removal of esophageal foreign bodies. Fish bones were the most frequently responsible foreign body and the cervical esophagus was the most frequent level of impaction. Decision-making based on clinical history and patient-referred symptoms revealed a positive esophagoscopy in 72% of the suspected cases. Radiographic studies gave falsely positive and falsely negative information in 30% of the cases. Rigid esophagoscopy was used successfully for foreign body removal in 99% of the cases. Average hospital stay was 3.2 days. No complications associated with the use of a rigid esophagoscope were found. PMID- 1754247 TI - Nd-YAG laser treatment of venous malformations of the head and neck: an update. AB - Malformations of the arterial and venous systems often are manifested in the head and neck. Low-flow venous malformations are generally benign lesions; however, complications, such as bleeding, obstruction, pain, or cosmetic deformities, may warrant surgical intervention. Treatment of these lesions can be challenging. Laser photocoagulation, particularly with the neodymium-yttrium aluminum garnet (Nd-YAG) laser, has been successful in the majority of patients, with minimal morbidity and good results. Thirty-two patients with low-flow venous malformations of the head and neck were treated with the Nd-YAG laser using low power density and intermittent short exposures in a punctate nonoverlapping technique. When possible, two glass slides were used to compress the lesion. There was excellent regression with minimal damage to the surrounding tissue. No major complications or morbidity, postoperative pain, or mortality occurred. Lesions occurring in some areas of the head and neck would not have been amenable to standard surgical excision. Follow-up period has ranged from 1 to 8 years. Nd YAG laser photocoagulation has proved safe and effective for treatment of low flow vascular malformations of the head and neck. PMID- 1754248 TI - Endoscopic CO2 laser arytenoidectomy for postintubation glottic stenosis. AB - Extended endotracheal intubation for assistive respiration can lead to cricoarytenoid joint fixation and subsequent bilateral midline vocal cord fixation--thus, complete glottic stenosis. Endoscopic CO2 laser arytenoidectomy was performed on 10 patients for bilateral midline vocal cord fixation caused by prolonged translaryngeal endotracheal intubation because of central nervous system respiratory insufficiency resulting from various causes. Eight of these patients had concomitant cricopharyngeal myotomy for associated severe upper pharyngeal dysphagia. All of these patients had successful return of airway, voice, and swallowing functions. The advantages of the CO2 laser for endoscopic arytenoidectomy are its facility, hemostasis, precision, and minimal scarring. PMID- 1754249 TI - Magnetic resonance imaging of the facial nerve during Bell's palsy. AB - Twenty-five patients with Bell's palsy were evaluated to assess the efficacy of gadolinium (Gd+)-enhanced MRI in determining: (1) the site of facial nerve enhancement, (2) the relationship between EMG findings and Gd+ MRIs, and (3) the usefulness of Gd+ MRI in predicting recovery of facial function. Eighteen of twenty-five patients had enhancement of the facial nerve during Gd+ MRI whereas seven did not. The most common areas of facial nerve enhancement were the labyrinthine, geniculate ganglion, and proximal tympanic segments of the facial nerve. EMGs were performed on ten patients who lost nerve excitability. The segments of facial nerve enhanced during Gd+ MRI varied in location and intensity in patients who maintained nerve excitability and in patients who lost nerve excitability. There was no correlation between EMG findings and location of facial nerve enhancement in patients who lost nerve excitability. The location of facial nerve enhancement during Gd+ MRI was not useful in predicting recovery of facial paralysis. PMID- 1754250 TI - Control of epistaxis in patients with hereditary hemorrhagic telangiectasia. AB - Twenty-nine patients were admitted to Pennsylvania Hospital between March 1984 and July 1990 with a diagnosis of epistaxis and hereditary hemorrhagic telangiectasia. Data were obtained through a retrospective review of the charts of these patients. Patients were treated for epistaxis with the CO2 laser, neodymium:aluminum garnet laser with a wavelength of 1064 nm (Nd-Yag), Nd-Yag laser with a wavelength of 532 nm (KTP), septodermoplasty, or any combination of these procedures. Patients underwent an average of 2.5 procedures each. Overall, 25 of 29 patients reported their symptoms had greatly improved with therapy. The average length of time without the need for further surgical intervention was 16.3 months for the Nd-Yag laser and 11.7 months for the KTP laser. Septodermoplasty using buccal mucosal grafts allowed, patients to avoid additional procedures for 24.4 months, which was twice as long as for standard septodermoplasty using split-thickness skin grafts. Although no therapy completely resolves the epistaxis, laser therapy combined with septodermoplasty enables the patients to gain excellent control of the epistaxis for several years. PMID- 1754251 TI - Management of otolaryngic patients susceptible to malignant hyperthermia without dantrolene. AB - Malignant hyperthermia (MH) is an adverse reaction most frequently associated with the administration of halogenated inhalational anesthetic agents and the depolarizing muscle relaxant succinylcholine. Characteristic findings are a hypermetabolic state accompanied by extreme hyperpyrexia, acidosis, rhabdomyolysis, and generalized muscle rigidity, often involving the masseter muscles. Dantrolene sodium, which was approved in 1979 by the FDA for use in the prevention of MH in high-risk patients, has neurologic and gastrointestinal side effects. At the Children's National Medical Center (CNMC), 24 children identified as being at risk for the development of a MH reaction were anesthetized for otolaryngic procedures by using "non-triggering" anesthetics and without use of dantrolene sodium. These patients represent 56% of all patients at risk for MH or masseter muscle rigidity (MMR) reactions during an 8-year period at the CNMC. There were no complications. Concomitant muscle biopsies were performed, and caffeine/halothane contracture studies were completed in 18 of these patients, demonstrating 11 susceptible or equivocal responses. The data suggest that children undergoing common otolaryngic procedures who are at risk for development of MH may be safely anesthetized without the use of prophylactic dantrolene sodium. PMID- 1754252 TI - Cranial nerve preservation in lesions of the jugular fossa. AB - The most significant objection to the proposal of lateral transtemporal cranial base surgery for the treatment of jugular foramen tumors is the perceived lasting morbidity attendant to aggregate cranial nerve loss. As techniques become more standardized and earlier diagnosis generates smaller tumors for treatment, outcome has become more predictable. Surgery has become the recognized management preference for these cranial base lesions. The purpose of this article is to assess the role of surgery in the treatment of jugular foramen lesions, as well as to review some of the technical highlights of conservation surgery, its clinical prerequisites, and reasonable expectations. We review 100 lateral skull base surgical cases of lesions involving the jugular foramen. The majority of these lesions--77 of 100--were paragangliomas. For these glomus tumors, cranial nerve preservation correlated well to tumor size and location. The diversity of the remaining 23 cases prevented any substantive conclusions. PMID- 1754253 TI - Midline nasal destruction in cocaine abusers. AB - Idiopathic midline destructive disease (IMDD) is a diagnosis of exclusion in patients who manifest midline nasal necrosis with no specific etiology such as infection, tumor, or Wegener's granulomatosis. Recently, a group of cocaine abusers has been identified that manifests a syndrome that mimics IMDD, but is less fulminant in its course. To better define the natural history of this syndrome, we reviewed the medical records, radiographs, and pathologic material from five such patients treated at the University of California, Los Angeles. Other causes of midline nasal destruction were excluded in each patient on the basis of histopathology, cultures, and laboratory tests. Biopsy material, available in four patients, demonstrated inflammation and necrosis without vasculitis. Treatment was conservative in four of the five patients, using antibiotics, local care, debridement, and cessation of cocaine use. During the follow-up period, progressive disease developed in one of the five patients, requiring radiation and steroid therapy. We conclude that the treatment of midline nasal destruction in cocaine abusers should initially be conservative, once other etiologies have been systematically excluded. PMID- 1754254 TI - Orbital wall fractures: evaluation and management. AB - Over a 49-month period, 121 orbital wall fractures were treated and 92 were followed for a median of 6.5 months (minimum, 3 months). Associated injuries included a 17% incidence of serious globe or optic nerve injuries and 13% incidence of lacrimal drainage disruption. Diplopia occurred in 23% and dystopia in 11%. Management was by observation alone in 14% and exploration in the remainder, with layered gelfilm for defects smaller than 4 cm2, alloplastic sheeting for defects to 6 cm2, and outer cortex of parietal bone for larger dehiscences. There were no decrements in vision from operation, dystopias were corrected to within 2 mm of normal, and diplopia persisted only in those with extraocular muscle paresis. There was no benefit to exploration of orbital wall defects smaller than 2.5 cm2 or with reduction of other midfacial fractures (e.g., malar) when neither dystopia nor entrapment was present, because defects not obturated in such cases had no sequelae. PMID- 1754255 TI - An evaluation of the head-shaking nystagmus test. AB - Head-shaking nystagmus can be observed in some patients with vestibular lesions. This nystagmus is transient and appears after 15 to 20 cycles of rapid head shaking. Horizontal head-shaking may be associated with a low-amplitude reversal phase, which follows the primary response. Several previous studies using active head movement have indicated that head-shaking nystagmus is a sensitive indicator of vestibular loss. In this study, the head-shaking nystagmus test using passive head movement was evaluated in 115 patients and 17 control subjects, using three examiners. The data indicate that using passive head movement, the head-shaking nystagmus test is neither sensitive nor specific enough for use as a screening test for vestibular loss. PMID- 1754256 TI - Characterization of cough associated with angiotensin-converting enzyme inhibitors. AB - Chronic cough is a side effect of the angiotensin-converting enzyme (ACE) inhibitor class of antihypertensives. The cough is thought to be a result of inhibition of the enzymes that break down some of the mediators of inflammation, such as the bradykinins and tachykinins. We report 20 patients with chronic cough caused by ACE inhibitors and some of the characteristics of the cough. The cough is typically dry, nonproductive, and worse at night. Interference with sleep is common and was severe in three patients. Women outnumbered men in this series: urinary stress incontinence developed in five, rectal and vaginal prolapse developed in one. Three patients felt they were incapacitated by the cough. Most had been on multiple medications; only oxycodone was reported to be effective in controlling the cough, and four patients thought they were addicted to that. All coughs resolved with withdrawal of the ACE inhibitor. Chronic cough is common among individuals taking ACE inhibitors. It may be severe and associated with complications. The incidence and potential severity is understated in drug information sources, and patients and physicians often fail to recognize cough as a drug side effect. PMID- 1754257 TI - The Caldwell-Luc procedure in 1991. AB - In the pre-antibiotic era, George Caldwell and Guy Luc both designed an operation to remove infected polypoid tissue from the maxillary antrum, as well as to provide drainage and ventilation of the sinus. With the development of antibiotics and the surgical endoscopes, many of the former indications for the Caldwell-Luc procedure have changed. However, the Caldwell-Luc procedure still offers optimal exposure for decompression of Grave's ophthalmopathy, pterygomaxillary space surgery, management of some maxillary trauma, removal of antral foreign bodies, repair of some oral-antral fistulae, management of maxillary osteomyelitis and benign maxillary tumors, and irreversible mucosal disease and endoscopic surgical failures. PMID- 1754258 TI - Computer-assisted instruction in otolaryngology: the use of a database for examination review. AB - A database of questions and answers has been developed to assist residents in reviewing current topics in otolaryngology-head and neck surgery. Each question/item has an associated answer, general category, specific category, and reference that allows cross-referencing on the computer system. The user can search the database for categories of interest and obtain a specific subset of questions. This allows an efficient means of knowledge acquisition and review for Board examinations. Additional data entry is also facilitated to expand the database as desired. Currently there are more than 2300 items in the database. PMID- 1754259 TI - Dynamic rehabilitation of the paralyzed face: III: Balanced coupling of oral and ocular musculature from the intact side in the canine. AB - We have recently demonstrated the feasibility of artificial agonist/antagonist coupling between intact facial and reinnervated strap muscles in the rabbit. The present study broadens this principle to involve bi-level cross-facial innervation. After severing the facial innervation unilaterally in four dogs, a nerve pedicle from a cervical motor nerve was implanted into the orbicularis oris and from the deep temporal nerve into the orbicularis oculi. After neurotization (5.6 months), the pedicles were electrically stimulated to verify muscular response. Graded contraction on the intact side was induced by stimulating the ipsilateral facial nerve with currents of various pulse widths. The resulting compression of a strain gauge on the intact face triggered a two-channel, opto isolated, pulse width-modulated stimulator to produce agonistic graded contraction at one level of the reinnervated side (e.g., oral) and reciprocal relaxation in its reinnervated counterpart (e.g., ocular). The sophistication of the present model--as compared to the original pilot study--brings us one step closer to dynamic human facial rehabilitation. PMID- 1754260 TI - Creation of a lobule: a simple technique. PMID- 1754261 TI - Malignant triton tumor of the head and neck. PMID- 1754262 TI - Diagnosis and treatment of the carotid artery in the middle ear. PMID- 1754263 TI - Atypical presentation of chylothorax following pharyngolaryngectomy with esophagectomy and gastric interposition. PMID- 1754264 TI - Isotretinoin for prevention of second primary squamous cell carcinoma of the head and neck. PMID- 1754265 TI - The endo-extralaryngeal needle carrier. AB - A laryngeal needle holder has been devised. This instrument will allow endoscopic insertion of sutures for lateralization of a paralyzed vocal cord or for fixation of endoscopically inserted stents or keels in laryngotracheal stenosis. The suture material is delivered by a curved nontraumatic cutting needle. After the needle is inserted in the desired endoscopic area, the tip protrudes through the anterior neck skin. The needle and distal suture are then pulled through the skin and the needle holder is withdrawn. The proximal portion of the suture is then inserted in the same fashion. Both ends of the suture are then fixed over buttons on the neck. The technique avoids the blind and cumbersome method of placing suture material from the skin to airway and back out to skin again. PMID- 1754266 TI - RBRVS: Boris Yeltsin, we need you. PMID- 1754267 TI - A family physician takes the state society's helm. PMID- 1754268 TI - An interview with Senator Wofford. PMID- 1754269 TI - From experience: fee schedule reforms (or: how I learned to stop worrying and love the system). PMID- 1754270 TI - Medicare fee reform still in question. PMID- 1754271 TI - Medicare reform includes global surgery package. PMID- 1754272 TI - Counseling to avoid AIDS. PMID- 1754273 TI - Are physicians' office laboratories reliable? PMID- 1754274 TI - Create an effective hiring routine. Health Care Group. PMID- 1754275 TI - Women in medicine: honored, but unheard. PMID- 1754276 TI - Assuming leadership in access to care. PMID- 1754277 TI - A national institute of nursing research? PMID- 1754278 TI - Sex and sexuality for the adolescent with a chronic condition. AB - Sexuality and sexual identity are developmental milestones that occur throughout the life span with sexual maturation usually occurring during adolescence. Parents and health care providers must prepare children with chronic conditions for this important component of adulthood to which they are entitled. PMID- 1754279 TI - Information on a shoestring: a practical database at an adolescent pregnancy program. AB - Adolescent pregnancy programs provide services to a socially high risk population with complex and continuing needs. Data describing the characteristics of the patient population is useful for directing program efforts, examining program outcomes, and documenting the need for additional services. The Rochester Adolescent Maternity Program has developed a simple, inexpensive data collection system in which demographic, social and reproductive information is routinely collected on all program patients. Such a system could be of use to other adolescent maternity programs. PMID- 1754280 TI - Nurses' attitudes toward sexuality in adolescent patients. AB - This descriptive study surveyed the sexual attitudes and nursing practice of 39 nurses who care for adolescents in a large metropolitan teaching hospital. A questionnaire containing 32 Likert scale items and 29 yes/no questions was used to survey the nurses' attitudes toward the sexuality of their patients and the use of sex education and counseling in their patient care. Frequency of answers generated by the participants was used to ascertain their sexual attitudes and characteristics of their nursing practice. Findings indicate that, although the sample recognized the importance of sexuality for the adolescent patient and were theoretically capable of addressing issues of adolescent sexuality, nurses were uncomfortable incorporating issues of sexuality, counseling, and education into their nursing practice. PMID- 1754281 TI - Fostering a spirit of inquiry in pediatric staff nurses. AB - Research-based practice is essential if nursing is to meet its mandate to society for effective and efficient patient care. The involvement of the clinical nurse is key to the conduct of research. PMID- 1754282 TI - Promoting non-tobacco use in childhood. AB - Smoking prevention programs are valuable in promoting life-long health behaviors in pediatric populations. Currently, social learning theory is the most common framework used for smoking prevention programs. Smoking prevention programs have reported varied results and have used different delivery and research techniques. The nurse is in an optimal position to plan and deliver a program and determine its effectiveness. PMID- 1754283 TI - Sudden, unexpected pediatric death: caring for the parents. AB - Sudden, unexpected death triggers acute grief in most survivors. This article provides an overview of that response and its manifestations in parents. Using the acute grief response as a framework for practice, guidelines are presented for assessment and intervention with parents in the acute care setting. PMID- 1754284 TI - Children and waterbeds. PMID- 1754285 TI - Meeting the challenge of immunizing the nation's children. AB - Achieving fully immunized status in the nation's pediatric population remains an elusive goal. A new campaign is underway to improve immunization coverage, and the nation's schools are logical sites to implement these projects. PMID- 1754286 TI - Leadership behaviors of pediatric nurse managers. AB - PURPOSE: To determine the leadership behaviors of firstline managers in pediatric hospital organizations. METHOD: A descriptive survey of 34 first-line managers in pediatric hospitals was done. A demographic questionnaire provided information about the nurses and their units. The Fiedler Leader Match Scales were used to collect data about the nurse manager's leadership behaviors. RESULTS: The nurse managers were slightly more task-oriented than people-oriented. The majority of the nurse managers perceived themselves to have high situational control. The match between the scales indicated that 21 of the managers were considered effective leaders. CONCLUSIONS: The majority of the nurse managers possessed effective leadership behaviors and were motivated by the completion of tasks. PMID- 1754287 TI - Adenosine. PMID- 1754288 TI - Pediatric management problems. Subacute otitis media with effusion. PMID- 1754289 TI - Adenosine in the pediatric population: nursing implications. AB - Tachydysrhythmias in the neonatal and pediatric age group can present a challenge to pediatric nurses. A new antiarrhythmic drug, adenosine, has proven useful as an acute tool in the termination and diagnosis of these potentially life threatening dysrhythmias. PMID- 1754290 TI - Bronchopulmonary dysplasia in the family: a longitudinal case study. AB - Oxygen-dependent infants with BPD are routinely sent home as soon as their conditions have stabilized. This article presents a prospective case study examining one family's adaptation to the birth, prolonged hospitalization, and home oxygen management of an infant with severe BPD. PMID- 1754291 TI - The process of quality management. AB - Hospitals are focusing their attention on quality improvement programs to meet the demands of the health care consumer. Managers need to be educated in the methodology and process of total quality management (TQM). PMID- 1754292 TI - Requirements and recommended dietary intakes of protein during infancy. AB - Two approaches have been used to arrive at estimates of the requirement for protein by infants. The factorial approach consists of adding the requirement for growth to the requirement for replacement of inevitable losses in urine and feces and from the skin. Protein requirement estimated in this way was 1.98 g.kg-1.d-1 during the 1st mo of life and decreased rapidly to 1.18 g.kg-1.d-1 by 4 to 5 mo of age, then remained at about that level to age 1 y. Believing that protein intakes of the breast-fed infant are near the level of the requirement, researchers used the intakes of breast-fed infants as a second estimate of requirement. Although intakes of protein by breast-fed infants during the first 2 mo of life are generally similar to the requirement values estimated by the factorial approach, intakes from 2 to 6 mo of age are less than the requirement values estimated by the factorial approach. Possible explanations for the discrepancy are presented. Recommended dietary intakes of protein somewhat greater than the requirements estimated by the factorial approach are proposed. These recommended intakes are less than those proposed by the FAO/WHO/UNU "safe levels of protein intake" and are less than the Recommended Dietary Allowances of the Food and Nutrition Board. PMID- 1754293 TI - Utility of breath ethane as a noninvasive biomarker of vitamin E status in children. AB - The purpose of our study was to determine if the ethane content of expired air could be a useful index of vitamin E status in children. Eight children with vitamin E deficiency secondary to chronic severe liver disease were studied: six of these children were treated with parenteral vitamin E (2-5 mg/kg/dose every 4 7 d). Measures of vitamin E status pre- and posttherapy were: serum vitamin E, 2 +/- 1 versus 7 +/- 1 micrograms/mL (p less than 0.001); serum vitamin E:total lipids, 0.3 +/- 0.1 versus 1.0 +/- 0.1 mg/g (p less than 0.001); and erythrocyte peroxide hemolysis test, 80 +/- 10 versus 6 +/- 12% (p less than 0.001). Fasting breath ethane in the patients pre- and posttherapy was 78 +/- 10 versus 31 +/- 11 pmol/kg/min (p less than 0.001). Breath ethane correlated negatively with serum vitamin E (p less than 0.042) and serum E:total lipids (p less than 0.004) and positively with the erythrocyte peroxide hemolysis test (p less than 0.003). Values for treated patients did not differ from those for fasted sibling controls (34 +/- 12 pmol/kg/min), postprandial sibling controls (31 +/- 12 pmol/kg/min), and healthy children sampled randomly, in the nonfasted state (21 +/- 14 pmol/kg/min). Breath ethane production in one patient (up to 168 pmol/kg/min) did not normalize after treatment of vitamin E deficiency until her selenium deficiency was corrected as well. We conclude that this noninvasive test can be useful as a screen for vitamin E deficiency in children and for ascertaining response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754294 TI - Intralipid increases lung polyunsaturated fatty acids and protects newborn rats from oxygen toxicity. AB - Intralipid, derived from soybean oil and containing a high percentage of n-6 family polyunsaturated fatty acids (PUFA) and also linolenic acid, an n-3 family PUFA, is commonly the first fat source provided to very low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female rats were fed either regular Rat Chow or fat-free diet containing 20%-Intralipid as the fat source for 3 wk before and then throughout pregnancy and lactation. One- and 5-d-old offspring of Intralipid diet-fed dams demonstrated significant increases in lung lipid n-6 family PUFA plus elevated linolenic acid compared with regular diet-fed offspring. These characteristic fatty acid patterns, apparent in total lung lipids, were even more pronounced in the triglyceride fraction compared with the phospholipid fraction. Associated with these fatty acid changes were significantly improved hyperoxic survival rates (89 out of 95 = 94% survival after 7 d of greater than 95% O2 exposure) in Intralipid offspring (versus 89 out of 106 = 84%, p less than 0.05 in regular diet offspring) and evidence of superior clinical/pathologic status. No differences in pulmonary antioxidant enzyme or surfactant system development, response of antioxidant enzymes to hyperoxic exposure, or lung prostaglandin E2, 6-keto PGF1-alpha or leukotrienes C4-F4 were present. These findings continue to support the hypothesis that increasing lung PUFA content may provide increased O2 free radical scavenging capacity, thus protecting against hyperoxic lung damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754295 TI - Protein turnover rates in sick, premature neonates during the first few days of life. AB - Rates of protein turnover were measured in 19 infants during the first few days of life while they were receiving i.v. glucose. The technique consisted of a continuous i.v. infusion of L-[1-13C]leucine to measure whole body leucine flux and determination of total urinary nitrogen excretion to assess leucine oxidation rates. Subsequent to each of the studies, the decision to start total parenteral nutrition (TPN) was made by the clinician concerned, with the result that seven infants did not start TPN and 12 did. There were significantly greater urinary nitrogen excretion (p less than 0.001) and lower rates of whole body protein synthesis (p = 0.024) and breakdown (p = 0.015) in those who did start TPN compared with those who did not. The marked difference in nitrogen excretion between the two groups suggests that this could be a useful determinant for deciding which neonate should start TPN. PMID- 1754296 TI - Effects of glucose infusion on leucine transamination and oxidation in the ovine fetus. AB - During fasting of the ewe, the rate of amino acid oxidation by the ovine fetus increases substantially. We hypothesized that the increase in amino acid oxidation derived mainly from reduced protein synthesis. We further hypothesized that fetal glucose supplementation would result in diminished amino acid oxidation. To test these hypotheses, nine ovine fetuses were infused with [15N,1 13C]leucine to determine the rates of leucine appearance and disposal. Simultaneously, the fetal uptake of leucine was determined. Animals were studied in the fed and fasted state. After baseline measurements, glucose was infused into the fetal inferior vena cava at a rate estimated to match the fetal glucose uptake. Results of these studies indicate that leucine nitrogen flux, leucine carbon flux and fetal leucine uptake were constant. Leucine oxidation was increased by 50% in the fasted state (6.3 versus 13.4 mumol/min); glucose infusion resulted in a 25% decline in oxidation (to 10.4 mumol/min) in the fasted state, but had no effect in the fed state. Mean leucine umbilical uptake during fasting was 9.3 mumol/min, 4.1 mumol/min less than leucine oxidation. These data suggest that leucine (and potentially other amino acids) may be in negative balance during maternal fasting, and can be spared by supplementation of the fetus with exogenous glucose. PMID- 1754297 TI - Oral L-alloisoleucine loading studies in healthy subjects and in patients with maple syrup urine disease. AB - Total body and renal elimination of L-alloisoleucine was assessed after oral loads (0.57 mmol/kg body wt) in four healthy subjects and in five patients with maple syrup urine disease (MSUD) of different degrees of severity. As judged from the fictive initial concentration, L-alloisoleucine is distributed evenly in the total body water space. In the controls, estimated half-time of total elimination was 9.2 +/- 2.2 h (n = 4). In the MSUD patients, it ranged from 26 h (mild variant) to about 8 d (classical type). Because of its low renal clearance rate, L-alloisoleucine was cleared through ketomethylvalerate to greater than 99% in normals and to at least 73% in the MSUD patients. Assuming small variation in the losses of ketomethylvalerate through L-isoleucine formation and through renal excretion, this test allows ranking of MSUD patients with regard to their residual in vivo branched-chain oxo-acid dehydrogenase activity. PMID- 1754298 TI - Tetrahydrobiopterin loading test in hyperphenylalaninemia. AB - Some cases of primary hyperphenylalaninemia are not caused by the lack of phenylalanine hydroxylase, but by the lack of its cofactor tetrahydrobiopterin. These patients are not clinically responsive to a phenylalanine-restricted diet, but need specific substitution therapy. Thus, it became necessary to examine all newborns screened as positive with the Guthrie test for tetrahydrobiopterin deficiency. Methods based on urinary pterin or on specific enzyme activity measurements are limited in their availability, and the simplest method, based on the lowering of serum phenylalanine after loading with cofactor, was discouraged by the finding that some dihydropteridine reductase-deficient patients were unresponsive. The preliminary observation that this limitation could be overcome by increasing the dose of the administered cofactor prompted us to reevaluate the potential of the tetrahydrobiopterin loading test in hyperphenylalaninemia. Fifteen patients, eight with ultimate diagnosis of phenylketonuria, three with 6 pyruvoyl tetrahydropterin synthase-, and four with dihydropteridine reductase deficiency, have been examined by administering synthetic tetrahydrobiopterin both orally, at doses of 7.5 and 20 mg/kg, and i.v., at a dose of 2 mg/kg. All the tetrahydrobiopterin-deficient patients, unlike those with phenylketonuria, responded to the oral dose of 20 mg/kg cofactor by lowering their serum phenylalanine concentration markedly below baseline to an extent easily detectable by Guthrie cards. This method allows for a simple screening method when enzyme or pterin studies are not available. PMID- 1754299 TI - Prenatal diagnosis and neonatal monitoring of a fetus with glutaric aciduria type II due to electron transfer flavoprotein (beta-subunit) deficiency. AB - The prenatal diagnosis of a male fetus with glutaric aciduria type II and the time course of metabolite urinary excretion, starting immediately after birth, are described. Prenatal diagnosis was undertaken at the 17th wk of gestation by immunoblot analysis and pulse labeling experiments of amniocytes and, retrospectively, by stable isotope dilution analysis of six metabolites in amniotic fluid. The results were as follows: 1) The immunochemical analysis on cultured amniocytes showed that the fetus, as the previous index case in this family, was affected with a deficiency of the beta-subunit of electron transfer flavoprotein. 2) Glutarate concentration was significantly increased in the cell free supernatant of the amniotic fluid. In the postnatal period, most of the organic acids and acylglycines characteristic of the disorder appeared in urine within a week, although an increased excretion of hexanoylglycine was the only biochemical abnormality detectable in the first urine sample collected at 9 h after birth. Growth and development of this infant were normal during the following 6 mo of life, when he was receiving oral supplementation with L carnitine and riboflavin. It should be underscored that transient abnormalities in routine blood tests (glutamic oxaloacetic transaminase, lactate dehydrogenase, and creatine phosphokinase) were present soon after birth, despite his asymptomatic clinical course. Early detection and aggressive treatment could be effective in such a form of glutaric aciduria type II. PMID- 1754300 TI - Developmental regulation of expression of C-reactive protein and serum amyloid A in Syrian hamsters. AB - The fetal and maternal concentration of various plasma proteins alters during pregnancy. Cells in the livers of fetal hamsters accumulate serum amyloid A (SAA) and C-reactive protein (CRP) mRNA, major acute phase reactants, when lipopolysaccharide is administered to the fetal circulation. No fetal SAA or CRP mRNA response is seen when the mother is stimulated at a remote site by endotoxin or a nonspecific inflammatory agent. In addition, cells of the fetal hamster liver do not respond by accumulating SAA mRNA when exposed to the specific cytokines, tumor necrosis factor, IL-1, and IL-6. CRP mRNA levels increased in fetal livers after administration of tumor necrosis factor and IL-1. These data suggest that cells contained in the fetal liver can respond during an acute phase reaction but that the capacity of some acute phase reactant genes to respond to cytokines may be developmentally regulated. Studies of immature hamsters after birth show that the responses of CRP and SAA genes to lipopolysaccharide, tumor necrosis factor, IL-1, and IL-6 are reduced when compared with induction of mRNA accumulation for these acute phase reactants in adult animals. PMID- 1754301 TI - Long-term effects of mild oligonephronia induced in utero by gentamicin in the rat. AB - Renal clearance studies and morphologic observations were performed in rats aged 14, 21, and 28 d and 3, 6, 9, and 12 mo born with a 20% reduction in nephron number after administration of 75 mg/kg/d of gentamicin to their mothers during the second half of gestation. Gentamicin was still present in urine 3 mo after birth. Morphologic damage characteristic of gentamicin accumulation was observed in the kidney on d 14 and 21. Adequate compensatory adaptation to oligonephronia occurred for glomerular function within 14 d of birth, but tubular phosphate reabsorption was significantly low on d 21. On d 28, no evidence of histologic or functional damage to the kidney was observed. At 3 mo, mesangial lesions were observed in rats of the gentamicin group, whereas they were rarely present in 6 mo-old control rats. Furthermore, glomerular sclerotic lesions were already evident in about 5% of the juxtamedullary nephrons. The same percentage of injured nephrons was not observed before 12 mo in controls. Complementary morphologic data obtained in 24-mo-old rats showed that glomerulosclerosis involved 40% of the juxtamedullary nephron population at this age in animals of the gentamicin group versus 21% in controls. It is concluded that in the young rats born with oligonephronia of gentamicin-treated mothers neither the gentamicin remaining in the kidney cells nor the injuries it caused them prevented compensatory adaptation of the kidney to a reduced number of nephrons. However, although this oligonephronia was mild, it might have been sufficient to cause early development of glomerular sclerosis in the adults. PMID- 1754302 TI - Short-term measurement of linear growth in preterm infants: validation of a hand held knemometer. AB - A hand-held electronic knemometer, resembling a pair of callipers, for measuring knee-heel length in preterm infants was developed to improve the accuracy of measuring linear growth velocity in infants. The measuring system is based on a magnetic encoder and has a resolution of 0.01 mm. The knee-heel length is recorded automatically when the pressure applied on the heel reaches a preset value. The result of a measurement sequence is expressed as the average of five sequential readings. The error of one measurement sequence was 0.82 mm, corresponding to a coefficient of variation of 0.8% or 2 d of growth in knee-heel length. It includes the technical error and an error component due to the correlation of the readings within a series. The estimated error on the measurement of the knee-heel growth velocity (expressed as mm/d), measured over a 3-wk period, was 0.04 mm, corresponding to a coefficient of variation of 8%. Longitudinal growth data from 11 healthy preterm infants (birth weight 918-1482 g) are presented. Knee-heel length velocity from birth until day of regained birth weight was similar to the velocity during the following weeks, showing that there was no deceleration of growth immediately after birth. In conclusion, the method is accurate and gentle in measuring linear growth velocity over short periods and can be useful in monitoring the progress of ill infants and in growth studies of preterm and mature infants, in which linear growth is a more relevant short-term outcome than weight gain. PMID- 1754303 TI - Postnatal development of flash visual evoked potentials in the jaundiced Gunn rat. AB - In this study, the postnatal development of flash visual evoked potential (VEP) has been monitored in the jaundiced (jj) Gunn rat model of neonatal hyperbilirubinemia to determine whether this evoked response is affected by bilirubin-induced neurotoxicity. VEP could first be recorded at 16 d of age. The jj rats exhibited prolonged wave latencies and lower wave amplitudes during the 3rd wk of postnatal life, when compared with their nonjaundiced littermates. There was no correlation at 21 d of age between VEP parameters and either bilirubin levels or body weight. About one third of the jj animals died between 21 and 28 d of age. The average VEP wave latencies at 21 d of age of the rats who were to die was prolonged compared with those of rats who survived till at least 28 d of age. Thus, the latency of VEP waves at the age of 21 d appears to be related to the further outcome of jj Gunn rats. Although wave amplitudes were lower in jj as compared with nonjaundiced 21-d-old animals, there were no amplitude differences between the jj rats who would die and those who would survive during the 4th wk of life. These findings may contribute to the understanding of the pathogenesis of bilirubin encephalopathy in the neonatal period. PMID- 1754304 TI - Bilirubin-induced changes in brain energy metabolism after osmotic opening of the blood-brain barrier. AB - Acute and residual effects of blood-brain barrier disruption and bilirubin on brain metabolism were studied in a rat model after osmotic opening of the blood brain barrier under pentobarbital anesthesia. Arabinose (1.5 M) was infused via the right external carotid artery over 30 s, resulting in opening of the barrier within the right hemisphere. Two min later, bilirubin was infused i.v. over 3 min, raising the serum bilirubin concentration to 37-44 mg/dL (633-752 mumol/L). The animals were euthanized at 15 min or 4 h by freezing the brain in situ. Opening the blood-brain barrier produced small changes in cerebral energy metabolism in some animals at 15 min. Compared with saline-infused control animals, two out of nine rats had decreased brain phosphocreatine and three out of nine developed increased brain lactate levels. Infusion of bilirubin in rats with a disrupted blood-brain barrier produced profound decreases in brain energy metabolites, glucose, and glycogen and a markedly increased lactate/pyruvate ratio at 15 min. The markedly increased lactate in the presence of normal or low pyruvate in bilirubin-treated animals indicates accumulation of NADH and probably reflects severe mitochondrial dysfunction. Four h after the arabinose/bilirubin infusions, the barrier would be expected to be repaired and bilirubin levels were negligible, but two out of five arabinose and three out of six bilirubin rats continued to have severely altered brain metabolism indicating residual brain injury in some animals. PMID- 1754305 TI - Hemodynamic response to volume stress in awake late-pregnant and nonpregnant rats. AB - The present study was designed to determine whether the often observed gestational rise in blood volume alters the hemodynamic response to volume stress relative to the nonpregnant state. Late-pregnant and nonpregnant Wistar rats, prepared with an electromagnetic flow probe around the ascending aorta and/or intravascular catheters were used for this study. One of the following sets of measurements were performed either before and after volume loading or before and after volume depletion (24 h thirst): 1) continuous monitoring of cardiac output, blood pressure, heart rate, and fluid balance (only during volume loading); 2) measurement of cardiac output and regional blood flows (microspheres); and 3) measurement of the inferior vena cava diameter (x-ray). Both rapid (bolus) and slow volume loading (infusion) led to a rise in cardiac output. The generated surplus in cardiac output was distributed to the kidneys, skeletal tissues, and intestines (only in nonpregnant rats), and was paralleled in the pregnant rats by a consistent fall in placental blood flow. Slow volume depletion had neither a consistent effect on cardiac output nor on its distribution, with even a preserved maturational rise in placental blood flow during the 24 h of thirst. Slow volume loading and depletion led to an increase and decrease of the caliber of the inferior vena cava, respectively. The nonnuterine hemodynamic response to all forms of volume stress had not changed in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754306 TI - Flow velocity wave forms in the human fetal ductus arteriosus during the normal second half of pregnancy. AB - Maximum flow velocity wave forms in the ductus arteriosus were studied longitudinally in 40 fetuses from 18 to 38 wk of gestation at 3- to 4-wk intervals. Median maternal age was 29 y (range 18-41 y), median parity was 1 (range 0-6). All flow velocity wave forms were obtained using a mechanical sector scanner with a continuous Doppler system (carrier frequency 3.5 MHz). The flow velocity parameters studied were peak-systolic, peak-diastolic, and time-averaged velocity and acceleration time. There was considerable variability in measurements between fetuses at any particular gestational age. An increase of ductal flow parameters with advancing gestational age was found. They showed no correlation with heart rate. These results suggest that the normal second half of pregnancy is characterized by a reduction in right ventricular afterload. This may be a result of decreased placental vascular resistance or increased pulmonary vascular flow. Acceleration time in ductal flow velocity wave forms was significantly higher than that observed in the pulmonary artery and ascending aorta, suggesting a lower afterload in the ductus arteriosus compared with the other two outflow tract vessels. PMID- 1754307 TI - Ventilatory sensitivities of peripheral and central chemoreceptors of young piglets to inhalation of CO2 in air. AB - In 20 piglets aged 2-12 d (mean 6.8 d) and anesthetized with alpha-chloralose urethane, we investigated the contribution of the peripheral and central chemoreceptors to the ventilatory response to inhalation of CO2 in air. For this purpose we used the dynamic end-tidal forcing technique, applying square-wave changes in end-tidal CO2 tension of 1.5-2.0 kPa at a constant end-tidal O2 tension of 15 kPa. Each response, measured on a breath-to-breath basis, was separated into a fast peripheral and a slow central component by fitting the sum of two exponentials to the measured ventilation. Each component was characterized by a CO2 sensitivity, a time constant, a time delay, and an apneic threshold. The results showed that in 2- to 12-d-old piglets the peripheral chemoreceptors are responsive to CO2 during air breathing. The contribution of the peripheral chemoreceptors in mediating the response to CO2 averaged 30 +/- 10%. Within this age range we could not demonstrate a significant correlation of the parameters characterizing the dynamic ventilatory response to CO2 with postnatal age. PMID- 1754308 TI - Lung volume, gas mixing, and mechanics of breathing in mechanically ventilated very low birth weight infants with idiopathic respiratory distress syndrome. AB - We assessed pulmonary function in 14 mechanically ventilated newborn very low birth weight infants with idiopathic respiratory distress syndrome by means of a face-out, volume displacement body plethysmograph and nitrogen washout analyses. Specially designed computer programs were used for calculations of lung volumes, ventilation, gas mixing efficiency, and mechanical parameters. In addition to very low compliance and moderately elevated resistance of the respiratory system, there were considerably impaired gas mixing efficiency and low functional residual capacity (FRC). No correlations between positive end-expiratory pressure and mean airway pressure versus compliance, resistance, or FRC could be found. Neither could correlations be found between FRC and compliance or FRC and the calculated right to left shunt. PMID- 1754309 TI - A plethysmographic method for assessment of lung function in mechanically ventilated very low birth weight infants. AB - We have developed and tested a plethysmographic method for assessment of lung function in mechanically ventilated very low birth weight infants during intensive care. Information about the mechanics of the respiratory system is obtained from the respiratory flow as measured by volume displacement plethysmography and from airway pressure measured in the artificial airway. Data on lung volumes, ventilation, and distribution of ventilation is obtained simultaneously by combining the respiratory flow measurements with nitrogen concentration analyses of the respiratory gas. No significant differences were found when the estimations of mechanical parameters and FRC were compared with reference methods and when determinations of the same parameters were repeated in the same subjects. The plethysmograph was shown to be safe and convenient to use, even in studies lasting several hours. PMID- 1754310 TI - [Problem of classification of rickets]. PMID- 1754311 TI - [Current classification of rickets in children (response to the discussion)]. PMID- 1754312 TI - [Results of the discussion regarding the classification of rickets]. PMID- 1754313 TI - [Urinary microflora and rational antibiotic therapy in pyelonephritis]. PMID- 1754314 TI - [Congenital and familial nephrotic syndrome in children]. PMID- 1754315 TI - [Results of using the principle of biological feedback in the rehabilitation of children with bronchial asthma]. PMID- 1754316 TI - [Etiology of a nephrotic form of primary chronic glomerulonephritis in children]. AB - As many as 91 children with the nephrotic and hematuric forms of primary chronic glomerulonephritis were examined for the presence of streptococcal infection and allergic diseases. It has been shown that as compared to patients with the hematuric form of chronic glomerulonephritis, those with the nephrotic form manifest a higher occurrence of A3, a dramatic rise of serum IgE and its dependence on the activity of glomerulonephritis. The data obtained may attest to the etiological role played by allergy in the development of the nephrotic form of glomerulonephritis. Frequently occurring colonization of hemolytic streptococcus in the fauces and the rise of the ASL-O titer in the blood serum seen in patients with the hematuric form of glomerulonephritis, its dependence on the disease activity suggest the streptococcal etiology in patients with that form in contrast to those with the nephrotic form. PMID- 1754317 TI - [Presence of markers of hepatitis B in patients with nephrotic syndrome]. AB - The purpose of the present work was to study the rate of HB viral infection from the standpoint of its pathogenetic importance in children with the nephrotic syndrome (NS). As many as 71 children aged 2 to 15 years with the NS were examined. 23 children with hematuric glomerulonephritic (GN) served as control. HB viral infection markers (HBsAg, anti-HBs, total anti-HBc and IgM anti-HBc) were detected in the blood serum by means of IEA in all the patients. The examinations made it possible to reveal material differences in the distribution of various combinations of VHB markers in children with the NS and hematuric GN. The combination of HBsAg and IgM anti-HBc turned out most characteristic for the NS, pointing to active NB viral infection. In patients with mixed GN, that combination was detectable twice as often. The data obtained attest te a high rate of the association of HB viral infection with GN, particularly with that running its course with the NS. In this case, the rate mentioned was significantly higher than in the population. A definite relationship between the activity of HB viral infection and the gravity of the NS suggests that VHB is implicated in the pathogenesis of GN. This suggestion may be indirectly supported by a far higher rate of HBsAg and IgM anti-HBc demonstration in patients suffering from membranoproliferative GN. PMID- 1754318 TI - [Intrarenal mechanisms of the regulation of homeostasis in children with nephrotic syndrome]. AB - Overall 40 patients with associated glomerulonephritis and the nephrotic syndrome were examined for renal response to the induced shifts in water balance: tests with 18-hour water deprivation characterizing concentration function of the kidneys, followed by water loading (22 ml/kg bw) which allows estimation of water excretion function and osmotic dilution. Osmotic concentration defect was revealed. It manifested in a decrease of osmotic concentration of the urine, a reduction of the concentration index according to creatinine. It should be mentioned that the more preserved was the magnitude of the concentration index the more this was ensured by sodium reabsorption, decrease of its excretion. Meanwhile osmotic concentration of the urine was determined by urea excretion. Study of partial functions in water diuresis discovered a dramatic lowering of sodium-free water clearance characterizing participation of the kidney in the maintenance of effective osmotic pressure of the plasma and reflecting the intensity of distal sodium reabsorption. PMID- 1754319 TI - [Endogenous vasoactive factors in children with nephrotic syndrome]. AB - In accordance with the results of examining 40 children with nephrotic and mixed glomerulonephritis, it has been established that in the pathogenesis of the nephrotic syndrome of paramount importance is imbalance of the output of renal prostanoids, manifesting in the predominance of the vasopressor and proaggregate fraction--thromboxane A2 and in the deficiency of its antagonist prostacyclin that exerts a protective action on glomerular filtration. Sodium and water retention in patients with the nephrotic syndrome favours an increase of the content of antidiuretic hormone and plasma renin activity. PMID- 1754320 TI - [Study of various factors of the pathogenesis of nephrotic edema in children with glomerulonephritis]. AB - As many as 26 children (20 boys and 6 girls) aged 2.5 to 15.5 years suffering from active nephrotic glomerulonephritis were examined for the intravascular liquid volume and antidiuretic hormone in blood plasma. In accordance with the magnitude of the circulating blood volume, 3 groups of patients were distinguished: group I included patients with hypervolemia, group II with hypovolemia, and group III with normovolemia. In the hypovolemic children, the nephrotic syndrome occurred at an earlier age as compared to the normovolemic children who developed it much later. The patients differed in the content of antidiuretic hormone and total blood protein. In the second group children, secretion of antidiuretic hormone was the highest one, whereas the level of total protein was the least one. A relationship was discovered between the pattern of the nephrotic syndrome and the efficacy of diuretic treatment. PMID- 1754321 TI - [Biochemical markers of atherogenesis in a nephrotic form of glomerulonephritis in children]. AB - A study was made of the regularities and changes in the fatty acid spectrum of total lipids of the blood serum, in interaction of carbohydrate lipid metabolism, and in the hypophyseal and thyroid system in 92 patients with the nephrotic form of acute and chronic glomerulonephritis. It has been discovered that the nephrotic form of glomerulonephritis is marked by a complex of changes in the fatty acid spectrum of the blood serum, in carbohydrate lipid metabolism at the sites of their conjunction, and in the hypophyseal and thyroid system which can be regarded as metabolic potentialities of atherosclerosis formation. PMID- 1754322 TI - [Urinary excretion of oxalates and urates in a nephrotic form of glomerulonephritis in children]. AB - Diurnal excretion of oxalates and urates with urine was examined in 31 children with nephrotic chronic glomerulonephritis. Active glomerulonephritis was demonstrated to be attended by hyperuraturia. Hyperuraturia and hyperoxaluria occurred in the treatment with immunosuppressants, diuretics and correlated with the impairment of other tubular functions of the kidneys. PMID- 1754323 TI - [Disorders of copper metabolism and dysfunction of the immune system in children with a nephrotic form of chronic glomerulonephritis]. PMID- 1754324 TI - [Morphology of the kidneys in children with primary nephrotic syndrome (lipoid nephrosis) before and after hormone therapy, studied by biopsy (light and electron microscopy)]. AB - Light and electron microscopies were employed to examine biopsy specimens from 15 children suffering from the primary nephrotic syndrome with minimal alterations in renal bodies. The studies were carried out at the height of the disease and in the stage of a clinical remission after prednisolone therapy. The author describes the development of ultrastructural changes in the glomerular filter, primarily of those in podocytes, under the conditions of highly selective proteinuria as well as during hormonal therapy that favours reparative processes and discontinuation of protein "leakage". It is assumed that the anionic layer of the glycocalyx of podocyte pedicles and l. rara ext. heparan sulfates of the basal membrane may play a role in the origin of selective proteinuria. PMID- 1754326 TI - [Nephrotic syndrome in childhood]. PMID- 1754325 TI - [Structure of interstitial nephritis in children]. AB - The authors provide the data on 24 cases of interstitial nephritis in children treated at the Nephrological Center of the city of Kuibyshev in 1986-1990. Describe the etiological structure of interstitial nephritis using the classification developed by N. A. Korovina and coworkers (1982), randomization according to the age, sex, and the disease course. Demonstrate the predominance of the postviral and toxicoallergic disease patterns in children of the early, preschool and junior school age. Estimate the importance of the types of urine proteinograms in the diagnosis of interstitial nephritis. PMID- 1754327 TI - [Early diagnosis and prognosis of bacterial tubulo-interstitial nephritis in children]. AB - The authors provide the data of a prospective follow-up of children with diseases of the urinary system organs. Analysis was made of the role of endogenous and exogenous factors in the formation of abacterial and bacterial tubulointerstitial nephritis (TIN) in children with predisposing conditions. It has been established that progression of the tubulointerstitial process can be seen in patients infected with causative agents capable of intracellular parasitizing and persistence in the body. Depending on the intensity of membranopathological and immune disorders the clinicopathogenetic manifestations of different stages of TIN are described in detail. It is shown that there is a possibility of early diagnosis of the bacterial stage of the disease on the basis of detecting the persistent microflora according to an assay of the antilysozyme activity of the causative agent and the urine content of beta-lysines in urine. The authors base the necessity of the preventive treatment of children with predisposing conditions and abacterial TIN to avert the formation and progression of bacterial TIN by means of agents that may prevent the persistence of causative agents and raising the efficacy of antiinfectious defence of the macroorganism. PMID- 1754328 TI - [Tubulo-interstitial syndrome in children with hemolytic-uremic syndrome]. AB - As many as 53 patients with the hemolyticouremic syndrome in the acute stage were examined and treated as were 29 patients in the long-term observation period (after 12-18 months). The characteristic features of the urinary syndrome in the acute and long-term observation period and the nephrobiopsy data 12-18 months after the hemolyticouremic syndrome point out that the tubulointerstitial component is of paramount importance in the impairment of the kidneys in patients with the hemolyticouremic syndrome. PMID- 1754329 TI - [Hepatitis B infection and primary glomerulonephritis in children]. AB - Out of 165 children presenting with renal pathology, HBV-infection was detected by RIA in 69.7% of children suffering from glomerulonephritis and in 30.8% of children with pyelonephritis. The infection manifested by the carriage of HBs antigen and persistent hepatitis. Unlike the control group (without HBv infection), in patients with HBv-infection, glomerulonephritis was characterized by the development of a prognostically unfavourable mixed form there of in children under 7 years, by rare cases of the onset of a complete remission consequent to immunosuppressive therapy, a decline of the level of serum IgG and the T lymphocyte count, a reduction of the helper/suppressor ratio to 1.21 at the expense of a decrease of the number of helpers, and a higher amount of lymphocytes expressing receptors to IL-2. PMID- 1754330 TI - [Effect of various infections on the development, course and outcome of glomerulonephritis in children]. AB - Bacteriological and virological tests were made at the disease onset and repeatedly in 100 children (66 boys and 34 girls) aged 2 to 15 years suffering from acute glomerulonephritis. The throat mucus was found to contain streptococci and staphylococci; direct immunofluorescence demonstrated antigens of influenza A1, A3, B virus, of parainfluenza virus, serotypes 1 and 3, of adenovirus and respiratory and syncytial virus; HBs-antigens, specific viral and bacterial antibodies were detected in the blood serum. At the onset of acute glomerulonephritis, 52.5% of the patients were diagnosed to have bacterial infection, 12.5% respiratory viral infection, and 27.5% mixed infection (respiratory viral and bacterial). Besides, 25.5% of the patients showed HBs antigenemia. HBs-antigenemia and mixed (respiratory viral and bacterial) infection were found to produce an adverse effect on the course and outcome of acute glomerulonephritis. Long-term circulation of some viral antibodies (mostly to parainfluenza-3 antigen) was revealed on repeated studies as was their untoward effect on the outcome of acute glomerulonephritis. PMID- 1754331 TI - [Synchronization of plasmapheresis and pulse therapy in the complex treatment of children with highly active glomerulonephritis]. AB - To suppress the activity of glomerulonephritis, lupus and primary chronic mixed one, 13 children received plasmapheresis synchronously with pulse therapy with cyclophosphamide or prednisolone. Plasmapheresis was carried out daily for 3 days. Six hours after the last session and on days 4 and 5 of the treatment pulse therapy was provided, followed by conventional intake of prednisolone per os in combination with azathioprine or cyclophosphamide. Beneficial therapeutic results were obtained in 10 patients within 3 to 6 weeks. The effect turned out insufficient in a patient with associated systemic lupus erythematosus, and rapid progressing nephritis and in a child with primary chronic glomerulonephritis of the mesangiocapillary type with fibroplastic transformation and persistent nephrotic syndrome. No therapeutic effect was attained in a patient with focal segmental glomerulosclerosis running its course with long persistent nephrotic syndrome. PMID- 1754332 TI - [Nephrotic syndrome in children: traditional and changing views on its pathogenesis and treatment]. PMID- 1754333 TI - [Diagnostic value of the polarographic test in children with a nephrotic form of chronic glomerulonephritis]. PMID- 1754334 TI - [Evaluation of the effectiveness of various programs of active therapy of primary glomerulonephritis with nephrotic syndrome in children]. PMID- 1754335 TI - [Effectiveness of the treatment of a nephrotic form of glomerulonephritis in children]. PMID- 1754336 TI - [Results of the treatment of glomerulonephritis in children with hepatitis B]. PMID- 1754337 TI - [Use of microelement and coenzyme preparations in the complex treatment of children with chronic pyelonephritis]. PMID- 1754338 TI - [Crigler-Najjar syndrome in an infant during the 1st year of life]. PMID- 1754339 TI - [Intravenous immunoglobulins in pediatric practice]. PMID- 1754340 TI - [Clinico-immunological aspects of gastrointestinal diseases in children]. AB - The data on the status of immunoregulation in 144 children with gastroduodenal pathology are provided as are indications for differentiated immunomodulatory therapy. As many as 100 children with celiac disease treated by means of long administration of the gluten-free diet were examined for the immunogenetic aspects and changes in the immune status. The authors demonstrate the incidence of recurrent intestinal disorders among 24 children with primary immunodeficiency states. PMID- 1754341 TI - [Rehabilitative treatment of children with bronchial asthma and recurrent bronchitis at the sanatorium stage]. PMID- 1754342 TI - [The pepsinogen-pepsin system in gastroduodenal pathology in children]. AB - The changes in the pepsinogen pepsin system reflect the degree of morphological alterations in the gastric mucosa. Based on the results of examining 98 children suffering from gastroduodenal diseases, the possibility is shown of distinguishing genetic and biochemical markers of duodenal ulcer. The characteristic features of the isoenzymic spectrum of pepsinogen-pepsin in different gastroduodenal diseases are demonstrated. PMID- 1754343 TI - [Clinico-pathogenetic aspects of peptic ulcer in children]. AB - Overall 98 children with duodenal ulcer were examined. It is shown that the rise of the products of lipid peroxidation in gastric juice enhances the aggressive properties of gastric juice and stimulates defence reactions of the gastric mucosa and duodenum. Lipid oxidation and the antioxidant systems of gastric juice were discovered to be disordered. The changes thus revealed are of diagnostic importance for detecting the recurrent nature of the disease. PMID- 1754344 TI - [Ulcerous and non-ulcerous gastrointestinal hemorrhage in children]. AB - The authors analyze the causes of gastrointestinal hemorrhages in 64 children aged 11 months to 15 years. 45 children had ulcerous and 19 non-ulcerous hemorrhages. The presence of gastrointestinal hemorrhages is an absolute indication for emergency esophagogastroduodenoscopy which appeared helpful in visualization of the source of hemorrhage in 60 out of the 64 patients (93.7%). 8 children underwent surgery, whereas in the remaining ones, hemorrhage was arrested by conservative treatment methods. PMID- 1754345 TI - [Absorption of carbohydrates in children with chronic enterocolitis]. AB - Absorption of carbohydrates was studied over time (according to the D-xylose test in 140 patients. Excretion of D-xylose with urine was found to be lowered in the overwhelming majority of the patients both during exacerbation and remission. Absorption of D-xylose was established to depend on the status of the upper alimentary tract, spreading of the process in the intestine, the character of morphological alterations in the intestinal mucosa, and so forth. These factors should be taken into account in the treatment administration. PMID- 1754346 TI - [Membrane-destructive processes in lesions of the biliary system in children]. AB - The authors analyze the data on lipid peroxidation in children with biliary system derangement. Lipid peroxidation was found to be significantly activated in children with exacerbation of chronic cholecystocholangitis and hypokinetic dyskinesia of the biliary tract. The data obtained suggest the development of the cytolysis syndrome in patients with inflammatory and functional diseases of the biliary tract. It is therefore recommended that the complex of treatment measures may include membrano-stabilizing agents. PMID- 1754347 TI - [Problems and perspectives of pediatric gastroenterology]. PMID- 1754348 TI - [Differential diagnosis of gallbladder diseases in children]. AB - To estimate the information content of different methods of diagnosing biliary diseases, 103 children aged 5 to 15 years, including 25 practically healthy children as control, were examined. Abdominal organs, particularly the liver and gallbladder were examined by echography. The duodenal contents was explored by microscopy of the sediment and biochemistry which included analysis in the vesicular and liver portions of the concentrations of phospholipids, activity of phospholipases A and C as well as measurements of creatine kinase, lactate dehydrogenase, alkaline phosphatase, C-reactive protein and of the diphenylamine index. Ultrasonography was found to be highly informative. The characteristic echographic alterations seen in dyskinesia of the biliary tract, dyscholias and chronic cholecystitis were defined. For differential diagnosis of dyscholia and chronic cholecystitis it is necessary to carry out biochemistry of the duodenal contents including measurements of phospholipids, activity of phospholipases A and C, alkaline phosphatase, creatine kinase, lactate dehydrogenase, C-reactive protein and the diphenylamine index. Based on the similarity of the alterations seen in children with different cholepathies, a concept is advanced of the mechanisms by which functional and organic diseases of the gallbladder are formed. PMID- 1754349 TI - [Distant thermography in the diagnosis of digestive organ diseases in children]. AB - The authors review the most urgent problems of alimentary diseases in children: diagnosis, differential diagnosis and early detection with the use of remote thermography, an up-to-date noninvasive and atraumatic research method. The method was demonstrated to be highly informative in diseases such as gastroduodenitis, peptic ulcer, chronic pancreatitis and others. The significance of remote thermography in revealing functional pathology of the alimentary organs in children is emphasized. PMID- 1754350 TI - [Results of the treatment of pyloric helicobacteriosis in children with gastroduodenal pathology]. PMID- 1754351 TI - [Immunomorphological criteria of the effectiveness of treatment of pyloric campylobacteriosis in children]. PMID- 1754352 TI - [Sanatorium-health resort treatment of children with biliary diseases]. PMID- 1754353 TI - [Immunization of children with long-term diarrhea]. PMID- 1754354 TI - [Staged treatment of children with digestive system diseases]. PMID- 1754355 TI - [Dysbacteriosis in children with gastrointestinal diseases]. PMID- 1754356 TI - [Clinical syndromes and treatment tactics in cow's milk intolerance in young children]. PMID- 1754357 TI - [Diagnosis of chronic pancreatitis in children]. PMID- 1754358 TI - [Nondrug treatment of chronic digestive system diseases in children]. PMID- 1754359 TI - [Treatment of duodenal ulcer in children]. PMID- 1754360 TI - Two-stage model of visual backward masking: sensory transmission and accrual of effective information as a function of target intensity and similarity. AB - A functional model is used to describe the effect of target intensity and target set similarity on backward visual masking. The model consists of two distinct stages of visual information processing. The first stage is related to sensory transduction and transmission and is assumed to require a finite and measurable amount of time during which performance remains at chance. The second stage, associated with central processing, is characterized by a negatively accelerated growth function reflecting the accrual of effective information. Results show that the duration of the transmission stage is inversely related to target intensity. Surprisingly, the rate of information accrual is an interactive function of both target intensity and target-set similarity. The pattern of results is consistent with the interpretation that both intensity and similarity mediate their effect through a common mechanism--the accrual of effective information. PMID- 1754361 TI - Informational masking and auditory attention. AB - Informational masking is broadly defined as a degradation of auditory detection or discrimination of a signal embedded in a context of other similar sounds; it is not related to energetic masking caused by physical interactions between signal and masker. In this paper, we report a systematic release from informational masking of a target tone in a nine-tone rapid auditory sequence as the target is increasingly isolated in frequency or intensity from the remaining sequence components. Improved target-tone frequency difference limens as isolation increases are interpreted as a reflection of increasingly focused auditory attention. The change from diffuse to highly focused attention is gradual over the frequency and intensity ranges examined, with each 1-dB increment in target intensity relative to the remaining components producing performance improvements equivalent to those produced by a 2% increase in frequency isolation. The results are modeled as bands of attention in the frequency and intensity domains. For attention directed by frequency isolation, there is a strong correspondence with auditory filters predicted by the power spectrum model of masking. These data also support the existence of an attention band of intensity, with a bandwidth of about 5-7 dB at the moderate levels used in this experiment. PMID- 1754362 TI - The object-detection effect: configuration enhances perception. AB - Line drawings used by Weisstein and Harris (1974) are seen as box-like three dimensional figures if the lines are arranged properly. A flat two-dimensional pattern is seen when these same lines are disarranged. A target line contained within the three-dimensional figure is identified more readily than is the same line contained within a two-dimensional figure. This finding was extended in the present experiments: The three-dimensional stimulus was detected more quickly than the two-dimensional stimulus, under conditions of visual backward masking. Three-dimensional stimuli were also classified more quickly than two-dimensional stimuli. Just as with the face-detection effect and the word-detection effect, object detection can be affected by the form of the visual stimulus. PMID- 1754363 TI - The effect of lightness contrast on the colored Muller-Lyer illusion. AB - Two subjects estimated the length of the central line in red and blue Muller-Lyer figures that were viewed both foveally and parafoveally. The illusion figures were defined by either lightness and hue differences between figure and ground or by a hue difference alone. For both subjects, the figures defined solely by hue produced larger illusions. Since depth-cue scaling and other cognitive factors did not cause the enlargement, it was concluded that the robust, hue-produced illusions resulted from contour interactions generated within parvocellular channels that are specialized for coding color. PMID- 1754364 TI - Induced motion of a fixated target: influence of voluntary eye deviation. AB - Induced motion (IM) was observed in a fixated target in the direction opposite to the real motion of a moving background. Relative to a fixation target located straight ahead, IM decreased when fixation was deviated 10 degrees in the same direction as background motion and increased when fixation was deviated 10 degrees opposite background motion. These results are consistent with a "nystagmus-suppression" hypothesis for subjective motion of fixated targets: the magnitude of illusory motion is correlated with the amount of voluntary efference required to oppose involuntary eye movements that would occur in the absence of fixation. In addition to the form of IM studied, this explanation applies to autokinesis, apparent concomitant motion, and the oculogyral illusion. Accounts of IM that stress visual capture of vection, afferent mechanisms, egocenter deviations, or phenomenological principles, although they may explain some forms of IM, do not account for the present results. PMID- 1754365 TI - The role of spatially selective attention in the tactile perception of texture. AB - During manual sensing of object attributes like surface texture, the tactile receptor sheet is conjointly activated at numerous loci. What is the role of spatially selective attention in perception under these conditions? We show that the requirement for spatial focus of attention is minimal in the detection of an abrupt change in texture. In contrast, spatial attention may help in a variety of other tasks of comparable difficulty. These include detecting the absence of a texture change at one of many loci, distinguishing its direction, and discriminating between different textures. Attentional demand appears to vary along a continuum in these tasks, rather than being all-or-none. PMID- 1754366 TI - Characteristics of the indirect McCollough effect. AB - Induction of contingent color aftereffects with a single chromatic grid sometimes results in an illusory color on a grid different from the one presented during induction. Such illusory color, contingently elicited by a noninduced grid, has been termed the indirect McCollough effect (indirect ME). We show that the indirect ME occurs only when the color complementary to the grid color is present during induction (either physically present or as a color afterimage), and that the indirect ME is seen only on gratings that are orthogonal to the induction orientation. These findings are in accord with the account of the indirect ME proposed by Humphrey, Dodwell, and Emerson (1989). We also show that characteristics of the indirect ME (seen following one-grid induction), both on induced and orthogonal orientations, are similar to those observed with the direct ME (seen following the usual two-grid induction procedure). Both procedures result in contingent aftereffects that display substantial retention and that do not display interocular transfer. PMID- 1754367 TI - Early and late selection in partial report: evidence from degraded displays. AB - In studies of iconic memory using the bar-probe task, subjects see a brief display of target letters and are probed by an arrow to report one of them. According to the classic early-selection account, subjects use the probe to select material for perceptual analysis from a precategorical (iconic) memory, but according to late-selection theories, subjects first identify the letters and then use the probe to select one letter for report from the set of categorized items. Pashler (1984) based his test for the locus of selection on a manipulation of display quality in previewed displays. He presented a target for 200 msec and then added a probe, together with the target, for an additional 150 msec. Reducing the target's stimulus quality increased response latency. If the subjects identified the characters before the probe appeared and then selected an item for report, the clarity of the original array should not have affected response latency. Hence, Pashler concluded that his subjects used the probe to select from a precategorical store (early selection). Pashler's experiment did not force subjects to rely on memory of the target; hence, although his experiment documented a situation in which subjects used early selection, it did not rule out late selection in studies of information persistence. We replicated Pashler's findings and, using his logic, showed that when subjects are forced to rely on memory of the target, they select from a categorized store. PMID- 1754368 TI - Perceptual organization and focused attention: the role of objects and proximity in visual processing. AB - The influence of the Gestalt grouping principles of similarity, closure, and proximity on the size of the response-compatibility effect was examined in a focused attention task. In three studies, subjects responded to a centrally located target and attempted to ignore adjacent distractors. The distractors, which served as targets on other trials, could be compatible, incompatible, or neutral with respect to the response of the target. In addition, the distractors and the target could be embedded in the same object, presented in the same color, presented on different objects, or presented in different colors. The typical response-compatibility effect (B. A. Eriksen & C. W. Eriksen, 1974) was found when the target and distractors were embedded in the same object or presented in the same color. Performance was poorer when the target was surrounded by response incompatible distractors than when it was surrounded by response-compatible distractors. However, the response-compatibility effect was eliminated when the target and distractors were embedded in different objects, even when the distance between the items was less than .25 degrees of visual angle. Furthermore, the response-compatibility effect was of intermediate size when the distractors were not grouped strongly with the target or with neutral flankers. The results are discussed in terms of space- and object-based models of visual attention. PMID- 1754369 TI - Attentional scanning and space errors. AB - Using the method of paired comparisons, pairs of simultaneous horizontal or vertical lines, with one line above and one below or one on the left and one on the right of a fixation point, respectively, were presented tachistoscopically for length comparison. Space errors were found to have a pattern similar to that of time errors. The tendency to guess the comparative response from the absolute magnitude of stimuli is proposed as a basis for time and space errors. Manipulation of attentional scanning, which implies a more frequent usage of this guessing strategy for one of the two lines in a pair, was shown to affect space errors. PMID- 1754370 TI - Auditory pattern perception: the effect of tone location on the discrimination of tonal sequences. AB - This study examined the effect of tonal location on the discrimination of sequences differing in the order of the tones and on their perceived grouping. The frequency range between the sequential tones was held constant. When all tones came from the same location, the sequence was rated as integrated, but when the higher frequency tones came from a different location than the lower frequency tones, the sequence was rated as segregated. Listeners discriminated the sequences in a 3IFC task. Discrimination performance was impaired when the sequence was split between two locations and tonal order was changed in only one location, even though the order of tones in different locations was changed. This result suggests that listeners have difficulty relating tones across locations or in different perceptual groups. Performance in this experiment is generally better than that observed by Barsz (1988), and it is suggested that the level of stimulus uncertainty explains this difference. PMID- 1754371 TI - Further evidence for Coren and Hakstian's "Methodological implications of interaural correlation: count heads not ears" and an alternative correction formula. AB - Coren and Hakstian (1990) identified a serious methodological problem that arises in auditory research because of interaural correlation. When measures from both ears of the subjects are pooled together in an experimental design that assumes independence of measures, there can be spuriously high apparent statistical significance. The present paper provides further evidence in support of Coren and Hakstian's argument and also derives a formula that effectively corrects inflated test statistics resulting from interaural correlation. This formula is a special case of a more general one that applies in many other experimental contexts in which nonindependence of measures is a problem. We found that statistical tests based on our formula have somewhat greater power to detect differences than the kind of correction method advocated by Coren and Hakstian. PMID- 1754372 TI - More than half of yeast U1 snRNA is dispensable for growth. AB - Yeast U1 snRNA (568 nucleotides) is 3.5-fold larger than its mammalian counterpart (164 nucleotides) and contains apparent sequence homology only at the 5' and 3' ends. We have used deletion analysis to determine whether the yeast specific U1 sequences play essential roles in vivo. Yeast cells carrying a deletion of more than 60% (355 nucleotides) of the single-copy U1 gene are viable, though slow-growing, while a deletion of 316 nucleotides allows essentially wild-type growth. The boundaries of the viable deletions define a dispensable internal domain which comprises sequences unique to yeast. In contrast, the essential 5' and 3' terminal domains correspond to phylogenetically conserved sequences and/or structures previously implicated in RNA:RNA and RNA:protein interactions. The minimal essential sequences of yeast U1 can be drawn in a secondary structure which resembles metazoan U1 in four of seven structural domains. PMID- 1754373 TI - Operation of an efficient site-specific recombination system of Zygosaccharomyces rouxii in tobacco cells. AB - Recombinase encoded by the R gene of pSR1 of Zygosaccharomyces rouxii mediates reciprocal recombination between two specific recombination sites (RSs) to induce excision or inversion of the DNA segment that is flanked by the RSs. We report here that site-specific recombination mediated by this system takes place effeciently in tobacco cells. To monitor the recombination events in tobacco cells, we have constructed two types of cryptic beta-glucuronidase reporter gene in such a way that recombination such as inversion of the construct or excision of the intervening sequence results in their expression. When these cryptic reporter constructs were transiently introduced together with the R gene by electroporation into protoplasts of tobacco cells, beta-glucuronidase activity was detected. The cryptic reporter genes, when stably resident in the chromosome of tobacco cells, were also activated by the R gene. Structural analyses of the genomic DNA isolated from these tobacco cells showed that the R protein did in fact catalyze precise recombination between two copies of RSs in tobacco cells, with resultant activation of the cryptic reporter genes. This observation provides the basis for development of a DNA technology whereby large regions of DNA can be manipulated in plant chromosomes. Potential uses of this recombination system are discussed. PMID- 1754374 TI - Liver specific transcription factors of the HNF3-, C/EBP- and LFB1-families interact with the A-activator binding site. AB - The A-activator binding site (AABS), present in the Xenopus A2 vitellogenin gene and several mammalian liver specifically expressed genes, interacts with different liver specific transcription factors including LFB1- and C/EBP isobinders. We have now isolated some additional proteins interacting with AABS and show that they are HNF3-isobinders. The interactions between AABS and members of the HNF3 family are confirmed by binding studies using bacterially made HNF3 alpha protein. Thus a short DNA module of 24 bp is able to bind proteins of three different families of liver specific transcription factors. Competition experiments in the cell free in vitro transcription show that AABS dependent transcriptional activation is mediated by transcription factors belonging to at least two different families, the C/EBP- and the HNF3-isobinders. Being able to mediate the action of several distinct transactivators, AABS may thus be a prototype for a novel kind of tissue specific promoter modules with unique regulatory capacities. PMID- 1754375 TI - Minisatellite binding protein Msbp-1 is a sequence-specific single-stranded DNA binding protein. AB - Msbp-1 is a minisatellite-specific DNA-binding protein. Using synthetic binding substrates, we now show that Msbp-1 binds not to double-stranded DNA, but exclusively to single-stranded DNA. Binding is specific to the guanine-rich strand of the minisatellite duplex, interactions with the cytosine-rich strand being undetectable by southwestern analysis. Furthermore, the binding site required for successful DNA-protein interactions appears to be two or more minisatellite repeat units. We have also isolated, by whole-genome PCR and cloning, one Msbp-1 binding site from the human genome. Again, the binding strand of this molecule contains a repetitive G-rich structure equivalent to that of a small minisatellite. These observations are discussed with respect to other single-stranded DNA-binding proteins known to play a role in recombination processes. PMID- 1754376 TI - A highly efficient, cell-free translation/translocation system prepared from Xenopus eggs. AB - We describe the use of a Xenopus laevis egg extract for the in vitro translation and post translational modification of membrane and secretory proteins. This extract is capable of the translation and segregation into membranes of microgram per millilitre levels of protein from added mRNAs. Signal sequences of segregated proteins are efficiently cleaved and appropriate N-linked glycosylation patterns are produced. The extract also supports the quantitative assembly of murine immunoglobulin heavy and light chains into tetramers, and two events which take place beyond the endoplasmic reticulum, mannose 6 phosphorylation of murine cathepsin D and O-linked glycosylation of coronavirus E1 protein, also occur, but at reduced efficiency. The stability of the membranes allows protease protection studies and quantitative centrifugal fractionation of segregated and unsegregated proteins to be performed. Conditions for the use of stored extract have also been determined. PMID- 1754377 TI - Ca(2+)-mediated inhibition of a nuclear protein that recognizes UV-damaged DNA and is constitutively overexpressed in resistant human cells: DNA-binding assay. AB - A nuclear protein that recognizes UV-damaged DNA was detected from HeLa cells using DNA-binding assay. Treatment of cells with Ca2+ ionophore (A23187) caused a dramatic inhibition of the damage-recognition activity. In contrast, in vitro treatment of nuclear extracts with agents that affect protein conformation (such as urea, NP40 and Ca2+) did not significantly affect on the damage-recognition activity. The Ca(2+)-mediated inhibition of UV damage recognition was reconstituted by the addition of the cytosolic extracts, suggesting that the Ca2+ effect does not directly act on the UV damage-recognition protein. The expression of the detected nuclear protein was increased in UV-resistant HeLa cells. In contrast, the level of this protein was dramatically reduced in UV-sensitive xeroderma pigmentosum group A cells. In addition, UV damage-recognition protein is resistant to RNase, and is independent of the previously identified proteins that bind cisplatin-DNA adduct. These findings implied that the recognition of UV DNA adduct is modulated by the intracellular level of Ca2+. PMID- 1754378 TI - Sequence specific protein binding to and activation of the TGF-beta 3 promoter through a repeated TCCC motif. AB - We have previously characterized the TGF-beta 3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta 3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these T-CCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta 3 mRNA, this region is responsible for mediating high level TGF-beta 3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta 3 promoter. Therefore, we provide strong evidence that high level expression of TGF beta 3 in A375 cells results from transactivation of the TGF-beta 3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue specific expression of this cytokine. PMID- 1754379 TI - Induction of S.cerevisiae MAG 3-methyladenine DNA glycosylase transcript levels in response to DNA damage. AB - We previously showed that the expression of the Saccharomyces cerevisiae MAG 3 methyladenine (3MeA) DNA glycosylase gene, like that of the E. coli alkA 3MeA DNA glycosylase gene, is induced by alkylating agents. Here we show that the MAG induction mechanism differs from that of alkA, at least in part, because MAG mRNA levels are not only induced by alkylating agents but also by UV light and the UV mimetic agent 4-nitroquinoline-1-oxide. Unlike some other yeast DNA-damage inducible genes, MAG expression is not induced by heat shock. The S. cerevisiae MGT1 O6-methylguanine DNA methyltransferase is not involved in regulating MAG gene expression since MAG is efficiently induced in a methyltransferase deficient strain; similarly, MAG glycosylase deficient strains and four other methylmethane sulfonate sensitive strains were normal for alkylation-induced MAG gene expression. However, de novo protein synthesis is required to elevate MAG mRNA levels because MAG induction was abolished in the presence of cycloheximide. MAG mRNA levels were equally well induced in cycling and G1-arrested cells, suggesting that MAG induction is not simply due to a redistribution of cells into a part of the cell cycle which happens to express MAG at high levels, and that the inhibition of DNA synthesis does not act as the inducing signal. PMID- 1754380 TI - Characterisation of a genomic clone covering the structural mouse MyoD1 gene and its promoter region. AB - We have isolated the mouse MyoD1 gene flanked by its promoter region by screening a genomic library with synthetic oligonucleotides. The structural gene is interrupted by two G + C rich introns. Transfection of the cloned gene inserted into an expression vector converts fibroblasts to myoblasts. Sequence analysis of about 650 bp of the 5' upstream region revealed the presence of several potential regulatory elements such as a TATA-box, an AP2-box, two SP1-boxes and a CAAT-box. In addition, there are three half palindromic estrogen response elements, a potential cAMP response element and various muscle specific elements such as a muscle-specific CAAT-box (MCAT) and four potential binding sites for MyoD1. Using S1 protection analysis the major start site of transcription in muscle and myoblast cells was mapped 3 bp upstream of the published cDNA 5' end. Promoter activity of the 650 bp upstream fragment was tested by in vitro transcription and by transfection analysis of myoblasts and fibroblasts. In all promoter test systems used, MyoD1 promoter activity was detected in myoblasts as well as in fibroblasts. Furthermore, DNA methylation was found to turn off MyoD1 promoter activity both in myoblasts and in fibroblasts. PMID- 1754381 TI - The Trypanosoma brucei DNA polymerase alpha core subunit gene is developmentally regulated and linked to a constitutively expressed open reading frame. AB - As an initial step towards the characterization of replicative DNA polymerases of trypanosomes, we have cloned, sequenced and examined the expression of the Trypanosoma (Trypanozoon) brucei brucei gene that encodes the DNA polymerase alpha catalytic core (pol alpha). The protein sequence contains the six conserved regions that have been recognized previously in eukaryotic and viral replicative DNA polymerases. In addition, we have identified a seventh region which appears to be conserved primarily in alpha-type DNA polymerases. The T.brucei DNA pol alpha core N-terminus is 123 and 129 amino acids smaller than that of the human and yeast homologue, respectively. The gene is separated by 386 bp from an upstream open reading frame (ORF) of 442 codons. Stable transcripts of the upstream sequence are detected in both dividing and non-dividing forms, while pol alpha transcripts are detected principally in dividing forms. Allelic copies of the T.brucei pol alpha region exhibit restriction site polymorphisms; one such sequence polymorphism affects the amino acid sequence of the T.brucei DNA pol alpha core. The T.brucei pol alpha region cross-hybridizes weakly with that of T.(Nannomonas) congolense and T.(Duttonella) vivax. PMID- 1754382 TI - Regulation of polyadenylation in hepatitis B viruses: stimulation by the upstream activating signal PS1 is orientation-dependent, distance-independent, and additive. AB - Hepatitis B viruses replicate by reverse transcription of a genomic RNA which harbors terminal redundancies. The synthesis of this RNA requires that transcription proceed twice through the polyadenylation (pA) site which, in mammalian strains, is flanked by the variant hexanucleotide UAUAAA and a T-rich downstream domain. These core elements are by themselves virtually defective in 3' end processing and require multiple upstream accessory elements which regulate pA site use. In ground squirrel hepatitis B virus (GSHV), one of these signals (PS1; -215 to -107 relative to UAUAAA) is transcribed only at the 3' end of genomic RNA and as such is analogous to retroviral U3 sequences. PS1 cooperates with other signals to enhance pA site use to very high levels and can be further sub-divided into two regions (A and B) which contribute equally to 3' end processing. Critical residues within PS1B have been localized to a 15 bp A/T-rich stretch which displays homology to other known upstream activating signals. A 15 bp segment within PS1A which has the identical A/T content but a divergent primary sequence plays a diminished role in processing. Furthermore, PS1 can activate GSHV core element usage autonomously. This stimulation has been shown to be additive since multiple copies of PS1 progressively increase polyadenylation, a phenomenon which also demands that PS1 exert its influence from a variety of distances from the hexanucleotide signal. PMID- 1754383 TI - Stereochemistry of methyl transfer catalyzed by tRNA (m5U54)-methyltransferase- evidence for a single displacement mechanism. AB - tRNA (m5U54)-methyltransferase (RUMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to the 5-carbon of uridine 54 of tRNA. We have determined the steric course of methyl transfer, using (methyl-R)- and (methyl-S)-[methyl-2H1,3H]-AdoMet as the chiral methyl donors, and tRNA lacking the 5-methyl group at position 54 as the acceptor. Following methyl transfer, ribothymidine was isolated and degraded to chiral acetic acid for configurational analysis. Transfer of the chiral methyl group to U54 proceeded with inversion of configuration of the chiral methyl group, suggesting that RUMT catalyzed methyl transfer occurs by a single SN2 displacement mechanism. PMID- 1754384 TI - Molecular cloning of the gene encoding the bovine brain ribonuclease and its expression in different regions of the brain. AB - In this paper we report the molecular cloning of the gene encoding the bovine brain ribonuclease. The nucleotide sequence determined in this work shows a high degree of identity to the homologous gene encoding the bovine pancreatic ribonuclease. Processing of the primary transcripts of these genes also follows a similar pathway, splicing of the unique intron in the 5' untranslated region occurs at corresponding positions. Expression of the bovine brain ribonuclease gene can be detected both at the transcriptional and translational levels in all the regions of the brain examined. PMID- 1754385 TI - Spontaneous deletions in Ig heavy chain genes: flanking sequences influence splice site selection. AB - The cell line G403.4.7, isolated as a spontaneous variant of the MPC-11 derived myeloma G403.4, produces a truncated gamma 2b HC protein, but no light chain (LC), and a single gamma 2b specific transcript of 2.4kb. This gamma 2b transcript consists of the VDJ and CH1 exons, the CH1 to Hinge (Hi) intervening sequence (IVS) and HI exon, part of the IVS between the two membrane exons M1 and M2, and most of the membrane 3' untranslated (UT) region. Even though the mature mRNA contains intronic sequences, it is abundant in the cytoplasm. Analysis of the gamma 2b genomic organization reveals that this unusual transcript results in part from two genomic deletions of 2.5kb and 588bp and in part from an altered splicing pattern. This altered splicing pattern is probably a consequence of the sequence alterations resulting from the genomic deletions. Analysis of these events provides some interesting insights into the mechanism of splice site selection and the evolution of introns and exons. PMID- 1754386 TI - A trace display and editing program for data from fluorescence based sequencing machines. AB - 'Ted' (Trace editor) is a graphical editor for sequence and trace data from automated fluorescence sequencing machines. It provides facilities for viewing sequence and trace data (in top or bottom strand orientation), for editing the base sequence, for automated or manual trimming of the head (vector) and tail (uncertain data) from the sequence, for vertical and horizontal trace scaling, for keeping a history of sequence editing, and for output of the edited sequence. Ted has been used extensively in the C.elegans genome sequencing project, both as a stand-alone program and integrated into the Staden sequence assembly package, and has greatly aided in the efficiency and accuracy of sequence editing. It runs in the X windows environment on Sun workstations and is available from the authors. Ted currently supports sequence and trace data from the ABI 373A and Pharmacia A.L.F. sequencers. PMID- 1754387 TI - RNA binding properties of the coat protein from bacteriophage GA. AB - The coat protein of bacteriophage GA, a group II RNA phage, binds to a small RNA hairpin corresponding to its replicase operator. Binding is specific, with a Ka of 71 microM -1. This interaction differs kinetically from the analogous coat protein-RNA hairpin interactions of other RNA phage and also deviates somewhat in its pH and salt dependence. Despite 46 of 129 amino acid differences between the GA and group I phage R17 coat proteins, the binding sites are fairly similar. The essential features of the GA coat protein binding site are a based-paired stem with an unpaired purine and a four nucleotide loop having an A at position -4 and a purine at -7. Unlike the group I phage proteins, the GA coat protein does not distinguish between two alternate positions for the unpaired purine and does not show high specificity for a pyrimidine at position -5 of the loop. PMID- 1754388 TI - Genetic organization of the KpnI restriction--modification system. AB - The KpnI restriction-modification (KpnI RM) system was previously cloned and expressed in E. coli. The nucleotide sequences of the KpnI endonuclease (R.KpnI) and methylase (M. KpnI) genes have now been determined. The sequence of the amino acid residues predicted from the endonuclease gene DNA sequence and the sequence of the first 12 NH2-terminal amino acids determined from the purified endonuclease protein were identical. The kpnIR gene specifies a protein of 218 amino acids (MW: 25,115), while the kpnIM gene codes for a protein of 417 amino acids (MW: 47,582). The two genes transcribe divergently with a intergeneic region of 167 nucleotides containing the putative promoter regions for both genes. No protein sequence similarity was detected between R.KpnI and M.KpnI. Comparison of the amino acid sequence of M.KpnI with sequences of various methylases revealed a significant homology to N6-adenine methylases, a partial homology to N4-cytosine methylases, and no homology to C5-methylases. PMID- 1754389 TI - Self-cleavage of a 71 nucleotide-long ribozyme derived from hepatitis delta virus genomic RNA. AB - Self-cleavage efficiency of ribozymes derived from hepatitis delta virus (HDV) has been shown to depend on the RNA structure, which in turn may be determined by the length of the considered sequences. Here we describe the construction and functional analysis of a 71 nucleotide-long RNA genomic fragment, Rz71, which carries an 18 nucleotide deletion in a very stable GC-rich stem-loop (stem IV), predicted to be present in several computer-derived secondary structure models. Rz71 is able to undergo self-cleavage under non-denaturing conditions (the t1/2 of the reaction at 37 degrees C is 3 min). The deletion, however, is not neutral, since under the same conditions the non-deleted ribozyme cleaves to 50% in less than 15 sec. Therefore, stem-loop IV seems to play a structural role, not being directly involved in the catalytic reaction, but contributing to the correct positioning of the catalytic core of the HDV ribozyme. Rz71 is the smallest self cleaving sub-fragment of HDV genomic RNA reported so far. PMID- 1754390 TI - H-DNA and Z-DNA in the mouse c-Ki-ras promoter. AB - The mouse c-Ki-ras protooncogene promoter contains a homopurine-homopyrimidine domain that exhibits S1 nuclease sensitivity in vitro. We have studied the structure of this DNA region in a supercoiled state using a number of chemical probes for non-B DNA conformations including diethyl pyrocarbonate, osmium tetroxide, chloroacetaldehyde, and dimethyl sulfate. The results demonstrate that two types of unusual DNA structures formed under different environmental conditions. A 27-bp homopurine-homopyrimidine mirror repeat adopts a triple helical H-DNA conformation under mildly acidic conditions. This H-DNA seems to account for the S1 hypersensitivity of the promoter in vitro, since the observed pattern of S1 hypersensitivity at a single base level fits well with the H-DNA formation. Under conditions of neutral pH we have detected Z-DNA created by a (CG)5-stretch, located adjacent to the homopurine-homopyrimidine mirror repeat. The ability of the promoter DNA segment to form non-B structures has implications for models of gene regulation. PMID- 1754391 TI - The structure of the gene coding for the mouse cell adhesion molecule uvomorulin. AB - We have recently shown that the Ca2+ dependent cell adhesion molecule uvomorulin is encoded by a single gene, localized on mouse chromosome 8. Here we describe the organization of the uvomorulin gene and give an initial characterization of the uvomorulin promoter. Uvomorulin is encoded by 16 exons, which are distributed over a region of more than 40 kb genomic DNA. The exon structure of the genes for uvomorulin and its chicken homologue L-CAM are nearly identical and thus highly conserved. The relationship between the exon structure and the structure of the uvomorulin protein is analysed. The initiation site of transcription of the uvomorulin gene is located 127 bp upstream of the translation start site in a GC rich region with no TATA-box, but with a GC-box in position -48 and a CCAAT-box starting at position -65 with respect to the transcription start site. 1.6 kb of the uvomorulin promoter (-1492 to + 92) confer cell type specific promoter activity to the CAT reporter gene. Homologies to known cis acting elements of other promoters are discussed. PMID- 1754392 TI - Induction of the Cyp1a-1 dioxin-responsive enhancer in transgenic mice. AB - Cyp1a-1, whose product, aryl hydrocarbon hydroxylase, assists in detoxification of polycyclic aromatic hydrocarbons, is the best characterized of the murine cytochrome P450 genes. The Cyp1a-1 dioxin-responsive enhancer region has been previously analyzed in vitro and found to induce expression of heterologous genes upon exposure of transfected cells to various aromatic hydrocarbons. A 2.58 kbp DNA fragment containing the Cyp1a-1 enhancer elements and promoter region was coupled to the chloramphenicol acetyltransferase (CAT) reporter gene and used to create transgenic mice. CAT assays were performed on tissues harvested from three different lines of transgenic mice following mock-induction or induction using the aromatic hydrocarbon, 3-methylcholanthrene. Basal levels of expression were detected in the spleen and small bowel of non-induced mice, with little or no expression detected in the liver. Treatment with 3-methylcholanthrene increased hepatic expression levels by as much as 10,000-fold. More modest levels of induction were also recorded in the spleen, small bowel, kidney, and lung. The results indicate that the dioxin-responsive enhancer region functions as a strongly inducible promoter in vivo. Differences in the response to induction between male and female mice suggest that Cyp1a-1 expression may be governed in a gender related manner. PMID- 1754393 TI - Sp1 is essential and its position is important for p120 gene transcription: a 35 bp juxtaposed positive regulatory element enhances transcription 2.5 fold. AB - Human proliferating cell nucleolar antigen p120 is expressed in tumor cells in the early G1 phase of the cell cycle. Deletion analyses of the essential cis acting region -537/-278 showed that a 58 bp sequence from -457 to -400 is an important cis-acting element. An Sp1 transcription factor binds to the sequence AGAGGCGGGG (-425 to -416) within the -458/-400 cis-acting region. Deletion of the Sp1 binding sequence eliminated transcription. Substitution of the Sp1 box(-437/ 406), containing the Sp1 recognition site, for the entire cis-acting region ( 537/-278) restored transcription only at a very low level (18%). Deletion of the 537/-278 cis-acting region followed by substitutions showed that the Sp1 box ( 437/-406) stimulated transcription 2.4 fold, when juxtaposed and downstream of a 35 bp (-472 GGGCGAGCGTAAGTTCCGGGTGCGGCGGCCGACTA -438) positive regulatory cis element (PRE) over that by substitution of the Sp1 box alone. When the -406/-278 sequence was downstream of the PRE-Sp1 box, transcription was stimulated 4.4 fold over that produced by substitution of the Sp1 box alone. These results suggest that Sp1 is essential and its proper position in the 5' flanking sequence, juxtaposed and down stream of a 35 bp positive regulatory sequence, is required for efficient transcription. PMID- 1754394 TI - Automated assembly of protein blocks for database searching. AB - A system is described for finding and assembling the most highly conserved regions of related proteins for database searching. First, an automated version of Smith's algorithm for finding motifs is used for sensitive detection of multiple local alignments. Next, the local alignments are converted to blocks and the best set of non-overlapping blocks is determined. When the automated system was applied successively to all 437 groups of related proteins in the PROSITE catalog, 1764 blocks resulted; these could be used for very sensitive searches of sequence databases. Each block was calibrated by searching the SWISS-PROT database to obtain a measure of the chance distribution of matches, and the calibrated blocks were concatenated into a database that could itself be searched. Examples are provided in which distant relationships are detected either using a set of blocks to search a sequence database or using sequences to search the database of blocks. The practical use of the blocks database is demonstrated by detecting previously unknown relationships between oxidoreductases and by evaluating a proposed relationship between HIV Vif protein and thiol proteases. PMID- 1754395 TI - Non-additivity of sequence-specific enzyme-DNA interactions in the EcoRI DNA methyltransferase. AB - We describe a novel strategy to characterize protein-DNA interactions involving monomeric enzymes such as DNA methyltransferases (Mtases). This strategy is applied to our investigation of the EcoRI DNA Mtase, which binds its double stranded recognition site 5'-G-AATTC-3' and methylates the central adenosine of each strand using S-adenosyl-L-methionine as the methyl donor. We show that prior methylation of adenosine in either strand does not perturb catalysis. In contrast, substrates substituted with deoxyinosine at either guanosine position (T-BMI5 and TI5-BM) show the minor groove residing N2 amino group of both guanosines contribute to DNA recognition since specificity constants for the modified substrates are reduced 13 and 39 fold. Similar analysis of a substrate containing deoxyinosine at both positions (TI5-BMI5) clearly shows that some communication occurs between the sites. To determine the extent to which structural changes in the DNA alone contribute to this lack of additivity, we performed DNA melting analysis of the singly and doubly substituted substrates, and also found non-additivity. Although our functional and structural analyses suggest that deoxyinosine incorporation causes long range conformational effects, the similarity of KmAdoMet for all substrates suggests that no large-scale structural changes occur in the Mtase-DNA-AdoMet complex. Our results support the following conclusions: 1) The non-additivity shown in this system contrasts with the widespread demonstration of additivity involving repressors [Lehming et al., 1990; Takeda et al., 1989; Ebright et al., 1987], suggesting that sequence discrimination by enzymes may involve more complex mechanisms. Further, this non additivity precludes quantitative assignment of individual interactions and we suggest that future analyses of this and related enzyme systems with base analogs include detailed information about the long range structural consequences of individual substitutions. 2) Although TI5-BM and T-BMI5 are shown to be radically different by thermodynamic analysis, the similar specificity constants with the Mtase suggest that the underlying structural differences (e.g., altered helical parameters of the DNA) are not critical for sequence-recognition. 3) The significance of minor groove Mtase-DNA interactions to specificity is confirmed. PMID- 1754396 TI - Differential DNA-binding abilities of estrogen receptor occupied with two classes of antiestrogens: studies using human estrogen receptor overexpressed in mammalian cells. AB - We have developed a transient transfection system using the Cytomegalovirus (CMV) promoter to express the human estrogen receptor (ER) at very high levels in COS-1 cells and have used it to study the interaction of agonist and antagonist receptor complexes with estrogen response element (ERE) DNA. ER can be expressed to levels of 20-40 pmol/mg or 0.2-0.3% of total soluble protein and all of the soluble receptor is capable of binding hormone. The ER binds estradiol with high affinity (Kd 0.2 nM), and is indistinguishable from native ER in that the receptor is capable of recognizing its cognate DNA response element with high affinity, and of transactivating a transgene in an estradiol-dependent manner. Gel mobility shift assays reveal interesting ligand-dependent differences in the binding of receptor complexes to ERE DNA. Receptors occupied by estradiol or the type I antiestrogen transhydroxytamoxifen bind to DNA response elements when exposed to the ligand in vitro or in vivo. Likewise, receptors exposed to the type II antiestrogen ICI 164,384 in vitro bind to ERE DNA. However, when receptor exposure to ICI 164,384 is carried out in vivo, the ER-ICI 164,384 complexes do not bind to ERE DNA, or do so only weakly. This effect is not reversed by subsequent incubation with estradiol in vitro, but is rapidly reversible by in vivo estradiol exposure of intact COS-1 cells. This suggests there may be some cellular process involved in the mechanism of antagonism by the pure antiestrogen ICI 164,384, which is not observed in cell-free extracts. PMID- 1754397 TI - Interaction of DNA-binding proteins with a milk protein gene promoter in vitro: identification of a mammary gland-specific factor. AB - The minimal 5' regulatory region of the sheep beta-lactoglobulin gene (BLG), as defined in transgenic mice, was used to identify nuclear factors which may be involved in milk protein gene expression in the lactating mammary gland. This 406bp promoter region was dissected into short, overlapping, double-stranded oligonucleotides to facilitate identification of the bound proteins. A variety of sites, for both known and previously undescribed DNA-binding proteins, are occupied in vitro. Some of these factors were investigated in detail. Two forms of nuclear factor I (NFI), which have different recognition site affinities, are present in nuclear extracts from lactating mammary gland and bind to at least 5 sites in this BLG control element. In addition, a factor (milk protein binding factor, MPBF) which is specific to extracts from both mouse and sheep lactating mammary gland binds to 3 BLG promoter sites and may be a milk protein gene transcription factor. PMID- 1754398 TI - Identification of a protein that interacts with the nuclear factor-1 (NF-1) binding site in cells that do not express NF-1: comparison to NF-1, cellular distribution, and effect on transcription. AB - We examined expression of nuclear factor-1 (NF-1) in different cell lines. Expression was low or undetectable in T and B lymphocyte cell lines, whereas fibroblasts and other adherent cell lines generally had a relatively high level of NF-1 mRNA. In cell lines that did not express NF-1, gel retardation assays, nevertheless, indicated complexes between a protein or proteins and the NF-1 site. These complexes were less abundant than those formed with NF-1, they migrated more slowly, and they appeared as single species instead of the multiple species observed with NF-1. NF-1 site-binding proteins were compared in the fibrosarcoma cell line HT-1080 (expressed the highest level of NF-1 in our study) and the B cell line Raji (does not express NF-1). UV-crosslinking studies indicated that the NF-1 site-binding proteins in both cell lines were similar in size. Proteolytic clipping band shift assays suggested that the Raji protein and NF-1 share structural similarity in their DNA binding domains, but are distinct proteins. The NF-1 site mediated transcriptional stimulation in cell lines where NF-1 is expressed; however, this element did not affect transcription in cell lines that do not express NF-1, suggesting that the NF-1 site-binding protein in these cells is functionally distinct from NF-1. PMID- 1754399 TI - Identification of a sequence-specific protein binding the 5'-transcribed spacer of rat ribosomal genes. AB - A novel 85-kD protein factor which interacts specifically with the 5'-transcribed spacer of rat ribosomal genes was identified using the gel mobility shift, DNase I protection and UV-crosslinking techniques. The binding site of the factor is located inside the 36 bp Alul-HindIII fragment of transcribed spacer, most probably in the region +94 to +115 with respect to the transcription initiation site. Factors giving very similar gel mobility shift patterns were also found in mouse and human cell extracts. Sequences resembling the binding site of this factor were revealed in corresponding regions of mouse and human ribosomal genes. The biological function of FTS remains to be elucidated. PMID- 1754400 TI - Primary and secondary structure of citrus viroid IV (CVd IV), a new chimeric viroid present in dwarfed grapefruit in Israel. PMID- 1754401 TI - Identification of a fourth nuclear factor I gene in chicken by cDNA cloning: NFI X. PMID- 1754402 TI - Cloning and sequencing of a mouse embryonal carcinoma cell mRNA encoding the tissue specific RNA splicing protein SmN. PMID- 1754403 TI - Sequence of human HMG2 cDNA. PMID- 1754404 TI - Molecular cloning of Xenopus elongation factor 1 gamma, major M-phase promoting factor substrate. PMID- 1754405 TI - A human homologue of the Escherichia coli DnaJ heat-shock protein. PMID- 1754406 TI - A novel substrate for assays of gene expression using chloramphenicol acetyltransferase. PMID- 1754407 TI - Improvement of PCR sequencing by formamide. PMID- 1754408 TI - A quick procedure for purification of functional recombinant proteins over expressed in E.coli. PMID- 1754409 TI - The direct screening of cosmid libraries with YAC clones. PMID- 1754410 TI - 'Turboprep' DNA: ultraquick preparation of plasmid DNA from single colonies for DNA sequencing. PMID- 1754411 TI - Heteroduplex formation as a means to exclude contamination in virus detection using PCR. PMID- 1754412 TI - Reconstruction of a large DNA fragment from coinjected small fragments by homologous recombination in fertilized mouse eggs. PMID- 1754413 TI - A rapid procedure for the screening of recombinant plasmids. PMID- 1754414 TI - A simple and efficient method for isolation of DNA fragments from agarose gel. PMID- 1754415 TI - Dinucleotide repeat polymorphism in the human thyroid hormone receptor beta gene (THRB) on chromosome 3. PMID- 1754416 TI - Dinucleotide repeat polymorphism at the D8S135 locus on chromosome 8p. PMID- 1754417 TI - Dinucleotide repeat polymorphism at D16S287. PMID- 1754418 TI - GT repeat polymorphism in the human proteoglycan link gene (CRTL1) promoter region. PMID- 1754419 TI - Non-synonymous polymorphism in the coding sequence of human 3-beta hydroxysteroid dehydrogenase (HSD3B). PMID- 1754421 TI - M1: Principles of management. Part (ii): How do you manage? PMID- 1754422 TI - Promise of named nurse not to be taken at face value. PMID- 1754420 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1754423 TI - Europe Against Cancer. PMID- 1754424 TI - Home truths. PMID- 1754425 TI - Women's work. PMID- 1754427 TI - Double prejudice. PMID- 1754426 TI - Kept in the dark. PMID- 1754428 TI - Body matters. PMID- 1754429 TI - Losing her eyes--care study. PMID- 1754430 TI - Mandatory updating. Why coercion does not work. PMID- 1754431 TI - Education--enriching lessons. PMID- 1754433 TI - Charting progress. PMID- 1754432 TI - Sperm banking. PMID- 1754434 TI - Defining quality in training institutions. AB - The views of nurse and midwife teachers occupy a crucial role in discussions about the quality of educational provision. So far, however, little information has been available on what the members of the profession think about this issue. In the course of a two-year research project commissioned by the ENB on performance indicators for training institutions, we asked teachers and their colleagues in all the English NHS regions to describe the characteristics of a high standard school. The study was conducted in the spring of 1988, that is, following the clinical grading review and the initiative to amalgamate school but before the NHS review and the acceptance of Project 2000. The data provided are an account of what is valued in schools of nursing and midwifery, for which a high degree of consensus was found among respondents. Management issues emerged as the top concern, followed by resources. Curriculum issues ranked third, closely followed by service links and professional/teacher issues. External links were of low importance. PMID- 1754435 TI - Careless words. PMID- 1754436 TI - Involving users in day care planning. PMID- 1754437 TI - Parent-held records of child development. PMID- 1754439 TI - Mental handicap nursing. A first-class service? PMID- 1754438 TI - Community link nurses in psychiatric care. PMID- 1754440 TI - Mental handicap nursing. Stand up and be counted. PMID- 1754441 TI - Mental handicap nursing. Community challenge. PMID- 1754442 TI - The Celtic challenge. PMID- 1754443 TI - Professional initiative stifled by cost-cutting management. PMID- 1754445 TI - Health of the nation. PMID- 1754444 TI - East meets West. PMID- 1754446 TI - Fulfilling potential. PMID- 1754447 TI - Quality through teamwork. PMID- 1754448 TI - Barred from treatment. PMID- 1754449 TI - Body politic. The case of the leaked draft. PMID- 1754450 TI - Homelessness--a home for Tom. PMID- 1754452 TI - Homelessness--left out in the cold. PMID- 1754451 TI - Homelessness--help for the outcasts. PMID- 1754453 TI - Arts in action--what's it worth? PMID- 1754454 TI - Pass the cranberry juice. PMID- 1754455 TI - Learning to sleep. PMID- 1754456 TI - Behind a screen. PMID- 1754457 TI - Mandatory updating--a lifetime commitment. PMID- 1754458 TI - Computing in practice. High-tech teach-in. PMID- 1754459 TI - More research needed to help women with HIV. PMID- 1754461 TI - Midwives' journal. Exercise in pregnancy. PMID- 1754460 TI - Midwives' journal. Labour and fasting. PMID- 1754462 TI - Midwives' journal. Unnecessary anointing. PMID- 1754463 TI - [Recent findings on the phenotype and function of T-lymphocytes in the human colostrum]. AB - Recent studies in our laboratory have demonstrated that the great majority of human colostral T cells display the phenotypic and functional characteristics of memory T lymphocytes, e.g. were able to proliferate in response to anti-CD3 and anti-CD2 monoclonal antibodies, and to a lesser extent, to the lectin mitogen phytohaemagglutinin. In addition, their production of interferon-gamma after anti CD3 and anti-CD2 stimuli was similar to that calculated in autologous blood lymphocyte cultures. More interestingly, the proportion of T lymphocytes bearing the gamma/delta T-cell receptor was found to be significantly higher in the mammary secretion than in autologous and heterologous blood samples. Furthermore, these cells were mostly delta-TCS-1+, thereby suggesting that they are actively motile cells capable of migrating from lymphoid to extra-lymphoid body tissues. The fact that the phenotypic pattern of colostral gamma/delta T cells is similar, if not identical, to that of the intestinal intraepithelial counterpart suggests that these cells might originate in the gut-associated lymphoid system and home selectively to the mammary gland late in pregnancy and throughout lactation. However, additional studies are needed to confirm whether milk T lymphocytes are actively involved in the adoptive lactation transmission of cellular immunity to the suckling infant. PMID- 1754464 TI - [Characteristic aspects of the therapy of heart failure in infancy. Review of the literature and personal data]. AB - The treatment of congestive heart failure in view of its pathophysiology can be divided in 3 parts: cardiokinetic therapy, diuretic therapy and vasodilator therapy. For each therapeutic component we report the latest findings and underline the peculiar aspects in the newborn. Furthermore we outline the basis for a rational use of the various types of drugs and indicate the future therapeutic prospectives. PMID- 1754465 TI - [Changes in the motor apparatus of the bronchial cilia. Comparative study of two types of myopathies: nemaline myopathy and the Werdnig-Hoffmann syndrome]. AB - The Authors during an extensive applications of nasal brushing in infancy according to Rutland and Cole, remarked--first time in literature--the contemporary presence in a child of the nemaline myopathy syndrome and immotile cilia syndrome. Supposing the possibility that in other myopathy may be present the same ciliary immotile syndrome, they studied with nasal brushing three cases of Werdnig-Hoffman syndromes: but they presented normal ciliary conformation. The Authors suppose that in case in future it should be found in other cases of nemaline myopathy the contemporary presence of dinein arms lack, it should be demonstrated that this syndrome takes derivation from a genetic alteration both of the muscular apparatus and the ciliary mobility system of bronchial epithelius. PMID- 1754466 TI - [Results of nasal brushing in the study of ciliary conformation and function in chronic bronchopneumopathies in childhood]. AB - For the frequent remark in childhood of relapsing bronchitis and/or broncho pneumonic sickness we resolved to use for the differential diagnosis the nasal brushing method according to Rutland (for samples of ciliated epithelium from the deep surface of the inferior nasal turbinate using a 2 mm diameter nasal brush. The samples were used for ultrastructural study of cilia. RESULTS: Children studied 22:14 (6-14) y.old with relapsing bronchitis, 4 with relapsing broncho pneumonitis, 1 Nemaline myopathy (n.m.) with heavy respiratory insufficiency; 3 Werdnig Hoffmann syndromes (W.H.). Control group of 4 normal children. In the control group and 14 relapsing bronchitis normal tubular pattern (9 + 2) and ciliary conformation were present; in the relapsing broncho-pneumonic syndrome group, 2 children presented deficiency of some brace dynein arms = chronic inflammation; in the Nemaline myopathy we noted total lack of interior dynein arms with random cilia orientation; in the 3 W.H. = normal cilia conformation. The authors noted for the heavy respiratory insufficiency of the Nemaline myopathy the presence of immotile cilia and discuss possibility that in all Nemaline myopathy syndromes this association may be present (a new syndrome?). The W.H. myopathy is characterized by normal cilia aspects and the respiratory insufficiency is caused by muscular respiratory insufficiency secondary to anterior spinal corn horn. In the Nemaline myopathy the same genetic defect can act in muscular fibres and on dynain arms (cytoskeleton). The technique described is suitable for processing epithelial brushings from other parts of the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754467 TI - [Comparison of high-dose immunoglobulin and cyclosporine in newly diagnosed diabetic children]. AB - A controlled trial was carried out on type I diabetic children to evaluate and to compare the clinical effects of two different kinds of immunotherapy: high doses intravenous gammaglobulin (IVIgG) and cyclosporine A (CyA). 30 newly diagnosed patients were admitted to the trial, 10 of whom served as controls (group A), 10 received 400 mg/kg b.w. of IVIgG on 5 consecutive alternate days and subsequently after 15 days and monthly thereafter for up to six months (group B), 10 patients received CyA 5-10/kg b.w. by mouth in two daily doses for a period comprised between 6 and 18 months (group C). Serum post-prandial C-peptide level was significantly higher after 6 months in group B and C than in group A; after 12 months, only group C showed significantly higher values. This difference was no longer significative at 18 and 24 months. Insulin requirement in the treated groups was significantly lower than in control group at 6 months, this difference was no longer significative at 12 months. We didn't find any difference concerning insulin requirement during the study comparing the two groups treated with the two different immunosuppressive therapies. In 3 patients in group B and in 3 patients in group C we didn't observe any appreciable response to immunosuppressive therapy (defined as insulin requirement greater than 0.5 UI/kg b.w. at 6 months and/or greater than 0.8 UI/kg b.w. at 12 months). We couldn't find any significant difference between responders and not responders to the immunosuppressive therapies regarding age, symptoms lasting before the diagnosis, weight loss, ketoacidosis intensity and serum post-prandial C-peptide level at the onset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754468 TI - [Neuroblastoma. Tumor rupture as an unfavorable prognostic factor]. AB - Since there is little information regarding the possible prognostic significance of tumor rupture in localized neuroblastoma, we have analyzed the clinical courses of 163 children registered from 1979-1990 in 12 italian pediatric oncology Centers participating in the Neuroblastoma Cooperative Group of the A.I.E.O.P. (Italian Association for Paediatric Haematology-Oncology). Ten instances (6%) of tumor rupture were described. Ruptures occurred preoperatively in one child, during the operation in 9; among these 9, two were provoked by the surgeon to allow radical tumor excision, 7 were accidental. Of these 10 children, 7 relapsed at 3-25 months (median, 8 months) from diagnosis. Relapses were local in 5 children (2 of the 5 died), disseminated in one (who died), local + disseminated in one (presently alive with disease). Two local relapses were followed by bony or haematologic spread at 4 and 8 months, respectively. Of the 7 children who relapsed, 2 are alive in complete remission at 29, 100 months, respectively; two are alive with disease at 3 and 65 months, 3 died at 8, 15 and 24 months, respectively. We conclude that rupture of a localized neuroblastoma is a factor predisposing to relapse and may compromise the chance of cure. The surgeon should be aware of the risks connected with this complication and make any effort to avoid it. PMID- 1754469 TI - [Juvenile rheumatoid arthritis with pauciarticular onset and HLA-A, B, DR in Italian children]. AB - Juvenile Rheumatoid Arthritis is a heterogeneous disease currently divided into different subtypes based on clinical characteristics. Significant alterations in frequencies of HLA-A, B and DR antigens have been described previously in children with pauciarticular onset Juvenile Rheumatoid Arthritis. We report the results of a study on 42 italian children with pauciarticular onset Juvenile Rheumatoid arthritis that partially confirm the literature data. PMID- 1754470 TI - [Comparison of radiology and 24-hour esophageal pH-monitoring in the diagnosis of gastro-esophageal reflux in various pediatric age groups]. AB - We retrospectively examined the 24 hour oesophageal pH study and the upper gastrointestinal (UGI) series of 67 children aged 5 weeks to 15 years. Thirty seven were suffering from gastro-oesophageal reflux (GER) and 27 from other diseases. Nineteen of them were younger than 6 months, 22 older than 18 months and the remaining 26 ranged from 6 to 18 month old. We found a high incidence of false positive and false negative results of the UGI series in all age groups. The number of false positive results was much higher in infants younger than 6 months (67%) than in the older children studied (27% between 6 and 18 months and 14% after 18 months). On the contrary, false negative results were absent in the first 6 months of life, but their number increased with age, up to 40% in children older than 18 months. Moreover, the 24 hour ph monitoring was found to have a high sensitivity (100%) and specificity (82-100%) in all age groups. For this reason, we believe than this examination could be used as the first line of investigation for the diagnosis of GER in all children, independently of their age. PMID- 1754471 TI - [Fluoroquinolones: pharmacokinetics and clinical use in pediatrics]. PMID- 1754472 TI - [Scoliosis: ten years' experience of screening]. AB - Scoliosis is a permanent lateral deflection of backbone, associated to a vertebra's rotation and twisting on their vertical axle, and it is one of more common diseases of pediatric age. It exist a great difference between the structural conformations, that are true pathologies, and the functional ones or paramorphisms, without bony alterations. Since about 80% of real scoliosis is idiopathic. The pediatrician's task is of precociously identify the appearance of a scoliotic bend and differentiate the structural and evolutive shapes from simple scoliotic posture. Therefore for ten years, in the preventive medicine programme of school age, we affected a scoliosis research in the secondary school using as clinical method the "bending test" that appraises three essential parameters: size's triangle, gibbus and limbs' asymmetry. Before examination an anamnestic form is compiled and the sexual maturity's degree is appraised. The subjects with suspect of scoliosis are asked to a subsequential control performed in our department's ambulatory service by a doctor of Scoliosis's Center of Pozzolatico (Florence), in order to decide whether to take radiographs and to define, if necessary, treatment. We verified 4453 pupils and of these the 8.9% has been asked to the specialist's control. Of these 106, namely the 2.8% of total pattern, have been X-rayed and 46, namely the 0.9% of total pattern, have been orthopaedically treated because affected by evolutive scoliosis. If we consider the last quinquennium's statistics, we remark that treatment's incidence is lower to 0.4% conforming to literature's data. We never observed false negatives whereas false positive have been only 0.8% of total pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754473 TI - [Evaluation and treatment of the enuretic child: eight years' experience]. AB - Enuresis is a common functional problem among children which is defined as a complete involuntary voiding of urine at an age which control should be present. Bed wetting generally resolves with increasing age, but the restriction in social life and the psychological secondary problems, so frequent in older patients, justify an appropriate treatment of the problem in the child over seven. At children's Hospital of Florence University an enuresis service exists since 1983, and during these years 541 children applied to the structure. 326 children completed the treatment, among these there were 202 boy and 124 girls with age between 6 and 19. All the patients have been initially helped only with conversation (motivational counseling) and 76 among them (23% of the whole) obtained permanent cure. The remaining 250 children were treated with the conditioning alarm system, always associated to periodic conversation, urine stop exercises and other psychological support (token economy, etc). There were 161 boys and 89 girls: 220 children had nocturnal primary enuresis and 30 secondary. The family history was positive in 77%. The results obtained of this kind of treatment after a follow-up of 6 months, were permanent recovery in 211 children (84%) and failure in 39 patients (16% of the cases). There have been 35 relaxes. Regarding the sex, no significant difference was noted. These positive results with the conditioning devices favor the view that the etiology of primary enuresis is mainly biologic. The bell alarm represents the most effective treatment for nocturnal enuresis included more than seven.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754474 TI - [Trisomy 18: phenotypic and biochemical variability]. AB - We report a case of Edward's syndrome showing some symptoms infrequently described in trisomy 18. The authors suggest that the phenotypic expression of symptoms rarely observed in the syndrome may be better interpreted as non specific consequence of the chromosomal imbalance, rather than directly related to genes on chromosome 18. A gene dosage effect for the enzyme Peptidase A, whose gene is mapped on chromosome 18, was also observed. PMID- 1754475 TI - [Computerized prototype of a screening test for the assessment of psychomotor development in childhood]. AB - The aim of Denver's screening test is to study the psychomotor development of normal or supposed normal children aged from 0 to 6 years and to suggest further investigation when an abnormal development is noticed. The test is divided into 4 sections: social behavior, fine motility, language, gross motility. The results are valid only if the test is done in a standardized manner. The aim of this paper is to describe the computerized prototype of the Denver test in use at the Divisional Pediatric Ambulatory of "A. Gemelli" University Policlinic in Rome. This test is used in the context of an automatized ambulatory management system called ARPIA, capable of interacting and guiding "non expert" user. The program performs the following functions: 1) General instructions for the execution and interpretation of the test. The original instructions of the test (1975 version) have been used. 2) Input, modification, exclusion of questions. The archive is organized in the following manner: questions are divided in the above four sections, according to the child, undergoing the test, age limit; the questions regarding information that can be asked directly to the parents or the display of a picture that better explains the test are marked. During the test the questions may be modified using a menu with a certain number of options to facilitate the use of the system. The questions to eliminate from the test may be appropriately marked and removed. The text is not physically deleted from the archive. The inverse operation of inclusion of a formerly removed question may be performed too.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754476 TI - [Neonatal screening for congenital hypothyroidism in a suburban hospital: assessment of eleven years' experience]. AB - Congenital hypothyroidism is one of the commonest endocrine diseases in infancy; the diagnosis is delayed it can lead to mental impairment. Since a precocious diagnosis, based on clinical symptoms and signs, is often difficult, screening at birth is very useful. Substitute L-T4 therapy presents some problems as it is impossible to assess the right dose before. The results of an eleven years long screening in a peripheral hospital are reported: 6408 babies were examined and congenital hypothyroidism was present in three cases, depending respectively on agenesia, ectopia and hypoplasia of the thyroid gland. PMID- 1754477 TI - [A diagnostic controversy: the significance of 14-6/sec positive spikes in clinical electroencephalography]. AB - There has been a great dealt of discussion as to the clinical significance of E.E.G. 14-6 per second positive spikes (14-6 PS), a short burst lasting one second or less which occurs during light sleep in monopolar recordings, mainly in the posterior temporal regions and usually involving the parietal and occipital regions as well, for the most part in unsymmetrical fashion. Early interpretations stress the epileptic nature of vegetative attacks in patients with an inter-critical E.E.G. reading characterized by 14-6 P.S. Subsequently, however, this hypothesis has been refuted, mainly because E.E.G. intra-critical recordings have never shown evidence of any sort of paroxysmal activity. At present time expert think that the presence of 14-6 PS may be merely an indication of an electrical alteration associated with disorders in the neurovegetative area. In order to evaluate the possibility of using them as a diagnostic marker of migraine equivalents and periodic syndromes, we reviewed wake and sleep E.E.G. recordings, carried out consecutively and hence not selectively, in 617 children aged 5-16 years. 14-6 PS were present in 109 children (17.6%), 63 of whom showed evident symptoms of periodic syndrome (headache, recurrent abdominal pain, cyclic vomiting, kinetosis, etc.); hence 46 E.E.G. recording were false positive. 510 children were lacking in 14-6 PS, 91 of these presented symptoms of periodic syndromes (false negative). 14-6 PS are hence a marker 40.9% sensitive, 90.1% specific, with a predictable value of 57.7%. The search for 14-6 PS in children with periodic syndrome is not particularly sensitive as a test, but it is fairly specific: it may well constitute an useful element in diagnosis. PMID- 1754478 TI - [Early decortication in the surgical treatment of pleural empyema in childhood: indications and results]. AB - Antibiotics and pleural drainage with continuous suction is effective in treatment of childhood pleural empyema. However a recognizable number of childhood pleural empyema fail to improve or to cure after this treatment. This study reviews our experience with 27 children over past 8 years. All patients were treated with antibiotics, seven with only pleural drainage, twenty with pulmonary decortication. Indications for decortication were: clinical and radiological failure after 4-5 days of treatment with pleural drainage and continuous suction; persistent fever; persistent respiratory distress; persistent signs of general illness; persistent loculated pleural effusions; worsening parenchymal disease. The clinical and radiological improvements following decortication were dramatic with immediate lung reexpansion and improvement of clinical course. The chest tubes were removed by the fifth postoperative day and the children were discharged by the seventh-nine postoperative day. There were no complications and no deaths. In our experience pulmonary decortication is a simple and effective treatment of childhood empyema in the advanced fibro purulent and/or early organizing phase with immediate and long-term excellent results. PMID- 1754479 TI - [Intracranial calcifications--seizures--celiac disease: a case presentation]. AB - The Authors report a case of coeliac disease which first appeared in a boy of 4, suffering from a seizure disorder. The bulky mass of fatty faeces led towards gastroenteric investigations (xylose-test, jejunum biopsy). The atrophy of the villi was clearly shown by the biopsy and a coeliac disease was easily diagnosed. The boy was prescribed a coeliac diet and no fits of generalized convulsions occurred during three years follow-up. Yet, while he was given a challenge free diet, they started to occur. A computerized axial tomography (TAC) carried out when he was eight and another when fifteen, evidenced bilateral, intracranial calcifications, cortical-subcortical, in the blood vessels, symmetrically located in the occipital region. The anticonvulsive therapy, started when he was 4, has never been interrupted. Now A.M. is 21 and still following an anticonvulsive polytherapy. Many tests were performed. The result of folic acid dosage carried out when he was 16, and badly follow a coeliac diet, was less than 2 ng/ml. A modification in the neurological symptomatology was noted during his puberal phase: fits of convulsions changed into daily crises of mind-failures. This feature is still present in his adult age. The case is reported for its clinical characteristics of neurological symptomatology associated with coeliac disease. The iconographical documentation evidences endocranial calcifications frequently connected with coeliac disease. PMID- 1754480 TI - [Psoriatic arthritis and celiac disease in childhood. A case report]. AB - A case of a girl followed up for 18 years is reported. At the age of two, the patient presented psoriasis and coeliac disease confirmed by biopsy and by laboratory data. She followed a coeliac diet and at the age of twelve she manifested a rheumatoid arthritis of the left knee without pain, confirmed by laboratory data (RA test, ANA test). In this period, the patient underwent another gastrointestinal biopsy after suspension of the diet; the structural alterations of the gastrointestinal tract being always present, she continued the diet associated with non steroidal antiphlogistic drug therapy for rheumatoid arthritis. The Authors remark the association of diseases, making a comparison with literature data and confirming the current hypotheses. It is interesting to observe that when the patient presented articular symptoms, there was the reappearance of the gastrointestinal symptomatology. Very interesting is the presence of psoriasis: in fact there is the problem whether this case is a psoriatic arthritis with coeliac disease or a juvenile rheumatoid arthritis with coeliac disease and psoriasis. At last, the Authors report the good results obtained by coeliac diet and non steroidal antiphlogistic drugs; a complete remission of articular symptoms and a good puberal and intellectual growth have been observed. PMID- 1754481 TI - [Hypoglycemia secondary to transitory hyperinsulinism in infancy: a case report]. AB - We refer about an infant with transitory hyperinsulinism who first developed symptoms at the age of nine month treated with diazoxide. The therapy was successfully discontinued at the age of twenty-one month. The follow-up until the age of 38 month revealed a normal growing up and a normal neurological development. The main cause of hypoglycaemia are discussed referring the different cases of hyperinsulinism of the recent literature. PMID- 1754482 TI - [Cerebral blood flow velocity after surfactant instillation in preterm infants]. PMID- 1754483 TI - The clinical utility of pulse oximetry in the pediatric emergency department setting. AB - Pulse oximetry provides a noninvasive, painless, accurate, and rapid method for measuring arterial oxygen saturation (SaO2). It has been shown to be valuable in anesthesia and critical care and recently has been used extensively in the outpatient setting. As is often the case with new technologies, little has been published on the basic issues of reliability, reproducibility, and effect on patient care. This prospective clinical study evaluated the basic principles of pulse oximetry in the pediatric emergency department setting and tested the hypotheses that pulse oximetry SaO2 measurements are reliable and provide valuable information, in addition to clinical and laboratory data which affect patient assessment and management. One hundred twenty patients were enrolled in phase 1 and 437 in phase 2 of the study. Pulse oximetry readings were reproducible with an intraclass correlation of 0.87. SaO2 measurements changed the assessed degree of illness in 188 (53%) patients; 47 (13%) were felt to be more ill and 130 (37%) to be less ill than at initial assessment. Sixty-nine (17%) patients were identified in whom SaO2 readings changed management plans; 27 (8%) were managed more aggressively (intubation, surgery, or admission), while 40 (11%) were managed less aggressively (discharged). In three cases, pulse oximetry was instrumental in the diagnosis of a serious illness. The results from this study indicate that pulse oximetry SaO2 readings are stable and reproducible and provide information which impacts significantly on patient assessment and management. PMID- 1754484 TI - A one-year prospective ED cohort of pediatric trauma. AB - During a 12-month period ending on November 30, 1988, data were collected on 4623 pediatric patients visiting a pediatric emergency department with trauma (excluding burns). Sixty-one percent were male. Common causes of the trauma included suspected child abuse (4%), organized sports (6%), nonorganized sports (4%), pedestrian motor vehicle accidents (MVAs) (3%), bicycle MVAs (2%), and automobile MVAs (3%). However, most of the incidents had none of the identified associated activities surrounding the trauma (60%). Incidents took place at home (41%), on the street (11%), at school (10%), and at a playground or park (10%). Injuries involved the external body (59%), extremity (26%), head or neck (13%), face (4%), chest (1%), and abdomen (2%) and were more common during the summer. Injury severity scores had a mean of 1.8 and were grouped as: less than 3 (80%), 3-6 (19%), and greater than 6 (1.6%). Factors associated with higher trauma severity included MVAs, water-related injuries, sports, streets, schools, parks, playgrounds, skateboards, skates, and alcohol. PMID- 1754485 TI - Improving knowledge of emergency physicians about child physical and sexual abuse. AB - The purpose of this project was to study the effect of self-instructional programs regarding physical and sexual abuse on the knowledge and case recognition of physicians. Data from a total of 191 emergency physicians revealed significant improvements from pre- to posttests, as well as increases in case recognition skills. More than 90% of physicians using each kit reported that the information had been valuable and that they would recommend the program to a colleague. The finding that knowledge mastery was high, combined with the recommendations of participating physicians, suggests that the programs tested are promising tools for educating emergency physicians about child physical and sexual abuse. PMID- 1754486 TI - Sickle cell screening practice in pediatric emergency departments. AB - Management of black children who present to a pediatric emergency department (ED) commonly requires knowledge of their sickle cell status. To determine the practice of sickle cell screening, 32 pediatric EDs were surveyed. Twenty-eight (88%) completed the survey, and, of these, 22 (79%) included sickle cell screening (differential solubility test for hemoglobin S) in the management of a black febrile six-month-old infant. To determine the method of screening for sickle cell disease, 60 consecutive black children less than two years of age, who presented to a pediatric ED, were reviewed prospectively. In 51 patients (85%), their condition warranted knowledge of their sickle cell status. Of these, parents of only nine (18%) children knew their child's sickle cell status. Thirty five (69%) patients had a presumptive newborn screening test for sickle cell disease, but only 15 presented between 8 AM and 5 PM on a weekday, the time during which the newborn screening laboratory could be telephoned for test results. For these same 15 patients, 13 had private physicians, but only three physicians had results of newborn sickle cell screening tests. The patients' hospital records were reviewed, and nine (18%) patients had prior sickle cell screening tests, but five of these tests were performed before the child was six months of age. To determine sickle cell status, 30 (59%) patients required a sickle cell screening test in the ED. ED screening detected three (6%) newly diagnosed sickle cell trait patients. In summary, sickle cell screening is recommended for young black children who present to an ED with fever or signs and symptoms supportive of sickle cell disease complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754487 TI - Plain abdominal radiography in the detection of acute medical and surgical disease in children: a retrospective analysis. AB - A retrospective review was performed to determine the utility of plain abdominal radiographs in evaluating children presenting to the emergency department. Clinical features, radiographic interpretation, and final diagnoses of 431 patients seen over one year were recorded. One hundred three (24%) patients had major diseases (ventriculoperitoneal shunt malfunction, foreign body ingestion, appendicitis, intussusception, bowel obstruction, necrotizing enterocolitis, toxic megacolon, blunt abdominal trauma, pyloric stenosis, and Hirschsprung's disease), while the remaining 328 (76%) had minor diseases. Radiographs were categorized as diagnostic, suggestive, normal, incidental, or misleading, with respect to the patient's final diagnosis. No single clinical feature was able to detect all diagnostic radiographs in patients with major diseases. Limiting radiographs to patients with prior abdominal surgery, suspected foreign body ingestion, abnormal bowel sounds, abdominal distention, or peritoneal signs identified all patients with radiographs diagnostic of a major disease while eliminating 48% of studies ordered. Our results suggest that restricting abdominal roentgenograms to patients with at least one of these features will detect most diagnostic radiographs in children with acute abdominal diseases. PMID- 1754488 TI - Gastrotomy and whole bowel irrigation in iron poisoning. AB - Ipecac and gastric lavage are questionable interventions for the overdose patient, and activated charcoal does not absorb iron. Gastrotomy and whole bowel irrigation have been described as unique interventions for this poisoning. We describe a patient who was treated with each of these. Because less than half of the iron was removed during surgery, and because the chelation requirement was modest, it is likely that whole bowel irrigation removed a significant amount of iron. We believe that this combined approach contributed to our patient's positive outcome. PMID- 1754489 TI - Skin necrosis complicating intraosseous infusion. AB - Bone marrow infusion is currently recommended as a useful technique for rapidly obtaining vascular access in critically ill children. Minor complications occur frequently, but serious complications of this technique are uncommon. We describe two patients with local skin necrosis complicating intraosseous infusion. To minimize the complications of this technique, we recommend placement verification before fluid infusion, careful monitoring for infiltration, and prompt removal after venous access is obtained. PMID- 1754490 TI - Emergency department management of blunt cervical tracheal trauma in children. AB - A case history of a young girl who sustained a small posterior laceration of her cervical trachea after blunt trauma is presented. She was brought to the emergency department (ED) by her parents roughly two hours after the incident with only minor symptoms. While in the ED, she developed significant airway compromise over a span of minutes. Orotracheal intubation was performed to secure her airway, and she responded to conservative management of her laceration. Her signs and symptoms, resolved, and she was discharged after five days. This case illustrates the importance of urgent evaluation and careful observation of patients with possible tracheal damage, as even very small tears have the potential to cause life-threatening airway compromise. PMID- 1754491 TI - Magnetic resonance imaging of acute symptomatic Schmorl's node formation. AB - The intraspongious herniation of intervertebral disk material into the endplate of a vertebral body was first described by Schmorl in 1927. Any process which weakens the cartilaginous endplate or the subchondral cancellous bone may predispose to the development of Schmorl's nodes. These include Scheuermann's disease, infection, metabolic disorders, neoplastic disorders, and degenerative disease. In the young individual, however, trauma may precipitate an acute focal and symptomatic endplate herniation by the well-hydrated and delineated nucleus pulposus. Magnetic resonance imaging (MRI) is the most sensitive imaging method for the detection of intervertebral disk disease and, thus, has facilitated the diagnosis of traumatic Schmorl's nodes. MRI was very helpful in diagnosing an acute, traumatic, symptomatic Schmorl's node when plain film radiographs and nuclear medicine bone scan were unremarkable. PMID- 1754492 TI - Suspected child sexual abuse. PMID- 1754493 TI - Infant with acute vomiting. PMID- 1754494 TI - Apnea monitors. PMID- 1754495 TI - Is preterm delivery genetically determined? AB - Surprisingly, the genetics of preterm delivery have received very little attention in the literature. Possible explanations are the inability to obtain accurate information on the length of gestation in family studies and the heterogeneous nature of this disorder. In contrast to the many studies which consider the relative contribution of both genetic and environmental variance to the total variance of birthweight, few studies have examined the genetic basis of the duration of gestation in man. It is argued that both genetic and epidemiological approaches are needed to separate the effects of heredity and the environment on the duration of gestation. PMID- 1754496 TI - Fumes from the spleen. PMID- 1754497 TI - Gestational duration and birthweight in white, black and mixed-race babies. AB - Using the 1983 United States population of single live births, birthweight and gestational duration were compared for babies of these different parental racial groups: both parents White, mother White-father Black, mother Black-father White, both parents Black. The four groups differed significantly with respect to the usual sociodemographic variables. Mean birthweight and mean gestational duration decreased in that order from the White-White reference group, and conversely there were increasing trends for low birthweight and preterm delivery. Adjustment for the usual sociodemographic variables did not alter these trends appreciably. Group differences were more strongly related to the mother's race than to the father's, and the trends were related to the mother's race. Because the father's race was significant, genetic factors are probably of some importance. The evidence from this study, together with the often-demonstrated relationships between low birthweight and preterm delivery with sociodemographic variables, and the short-term downward secular trends in low birthweight, support the concept that non-genetic maternal factors are more important for these abnormal outcomes. But because neither the usually utilised sociodemographic variables nor genetic factors seem to explain much of the group differences, new approaches are necessary to understand why, irrespective of ethnic group, some women are at excess risk for suboptimal birth outcome. PMID- 1754498 TI - Antecedents of macrosomia. AB - Antecedents of high birthweight (macrosomia) were studied using the state birth certificates of White singleton infants born in three large metropolitan counties of Washington State from 1984 to 1986. Cases consisted of 2082 live-born macrosomic infants, defined by a birthweight of over 4.5 kg. A random sample of 4440 live births with birthweights of 2.5-4.0 kg was selected as a comparison group. Estimates for the independent risks associated with gestational and established diabetes, male sex, parity, duration of gestation, maternal smoking during pregnancy, maternal age, and median income of maternal residential area were obtained and combined in a single logistic model. Maternal smoking was associated with a decreased risk of macrosomia (OR 0.4, 95% CI 0.3-0.5). Established diabetes (OR 6.4, 95% CI 2.7-15.4), gestational diabetes (OR 3.2, 95% CI 2.1-5.1) and male sex of the infant (OR 2.4, 95% CI 2.2-2.7) were associated with an increased risk. Increasing parity was related to an increasing risk from para one (OR 1.4, 95% 1.2-1.6) to para six and greater (OR 3.3, 95% CI 1.5-7.4). Increasing duration of gestation was associated with an increasing risk from 33 36 weeks (OR 0.8, 95% CI 0.5-1.2) to 43-45 weeks (OR 3.3, 95% CI 2.5-4.2). Maternal age, median income of maternal area of residence, and maternal marital status were not significantly associated with macrosomia. PMID- 1754499 TI - Prenatal exposure to prescribed drugs in Tennessee Medicaid, 1983-1988. AB - This report describes the prenatal exposure histories of 107,804 women to prescribed drugs other than vitamins, iron and other minerals. The data were obtained from Tennessee Medicaid pharmacy files linked to birth and fetal death certificates for 1983-1988. The utility of these data to other investigators in predicting power or estimating sample size for studies of drug exposure in pregnancy associated with adverse birth outcomes is discussed. PMID- 1754500 TI - Cohort reconstruction: which infants can be restudied at school age? AB - Longer-term follow-up of infants with specific health concerns, such as low birthweight, is critical to assessing the effect of medical interventions. This report examines the approach of reconstructing previously studied cohorts in terms of the factors discriminating between respondents and non-respondents. Follow-up was attempted during 1987-1988 for 1875 children born during a 6-month period in 1978 in three geographically defined regions in the United States, for whom 1-year assessments of health and developmental status were obtained at 1 year of age as part of a previous study. For a 25% sample, participation involved a clinic visit for developmental assessments; for the remainder an interview by telephone or home visit. Follow-up was obtained for 72.5% of the cohort. Refusal rates were low (7%); most non-response was due to an inability to locate the families. Predictors of non-response reflected primarily low socio-economic status; completion rates were not influenced by mode of assessment. The role of a tracing agency is discussed. We conclude that cohort reconstruction is feasible with response rates comparable to some prospective studies with ongoing cohort maintenance. PMID- 1754501 TI - Birth defects monitoring in California: a resource for epidemiological research. AB - The California Birth Defects Monitoring Program maintains a population-based birth defects registry of structural congenital malformations, monitoring over 600,000 resident births annually. Cases are actively ascertained from hospitals and genetic centres throughout California and from selected facilities in adjacent states. Field staff identify presumptive cases from careful review of medical records. Diagnostic and demographic information is collected from in patient and genetic centre medical charts for children diagnosed with major structural malformations between conception and 1 year of age. The application of these data to epidemiological investigations of birth defects is described in the context of prevalence studies, aetiological studies and evaluative studies, and the strengths and limitations of the registry data are discussed. PMID- 1754502 TI - The Bedouin Infant Feeding Study: study design and factors influencing the duration of breast feeding. AB - A longitudinal study of infant feeding practices, growth and morbidity among Bedouin Arab infants residing in the Negev, Israel, was conducted during a 3-year period (1981-1983). Follow-up samples were restricted to healthy newborns. The majority of newborns are breast fed at birth but, by 2 months, 50% are also introduced to a milk supplement. Based on the bivariate analysis using the logrank test to examine the factors associated with exclusive versus partial breast feeding during the first 6 months, those born during the wet cool months are exclusively breast fed longer than those born during the dry season. More traditional women, living in tents rather than houses or huts, exclusively breast feed for at least 6 months. In a multiple logistic regression model, parity, house type and birth season are independently associated with the odds of exclusively breast feeding for the first 6 months of life. Factors influencing the duration of any breast feeding for the first 18 months include: house type, place of residence, birthweight, and whether the infant was stunted at 6 months. PMID- 1754503 TI - Association between holoprosencephaly and exposure to topical retinoids: results of the EUROCAT Survey. PMID- 1754504 TI - Joel Kleinman (1946-1991). PMID- 1754505 TI - Experimental cerebral atherosclerosis in the rabbit. Scanning electron microscopic study of the initial lesion site. AB - The development and initial lesion sites of cerebral atherosclerosis were studied in hypertensive rabbits fed 0.5 g/day cholesterol in their diet. The earliest lesions developed at remarkably localized areas of the basilar artery-posterior cerebral artery Y-bifurcation (area A) and vertebral arteries-basilar artery confluence (area B). These findings were obtained from a thorough scanning electron microscopic survey of the dorsal surface of the cerebral artery segment covering from the vertebral arteries to the posterior cerebral arteries. By light microscopy intimal lesions were mainly composed of accumulations of foam cells and smooth muscle cells. Electron microscopically foam cells accumulated in the intima resembled those of a monocyte-macrophage lineage. Early lesions involving only a few endothelial cells with adherent leukocytes occurred at the dividing and confluent portions of the endothelial arrays formed in areas A and B, respectively. The results indicate that hypertension coupled with hypercholesterolemia induces atherosclerosis in particular vulnerable regions of the cerebral arteries. PMID- 1754506 TI - Dermatofibrosarcoma protuberans. A histological and ultrastructural study of 11 cases with emphasis on the study of recurrences and histogenesis. AB - Eleven cases of dermatofibrosarcoma protuberans (DFSP) (6 male: 5 female; mean age +/- SD: 48.7 +/- 16.1 years) were reviewed in an attempt to correlate the histological and ultrastructural findings with the recurrence pattern of these tumours and to shed light on their histogenesis. Six (54.5%) of the tumours recurred: 3 with a similar appearance to the primary tumours, 2 with fibroblastic malignant fibrohistiocytic pattern (F-MFH), and one with fibrosarcomatous features (F), confirmed ultrastructurally. In one primary tumour with associated F features there were two recurrences. The ultrastructural findings of 6 primary tumours (2 with and 4 without recurrences) showed a predominance of primitive mesenchymal cells. The comparison between the features (sex, age, site, necrosis, mitotic rate size) of recurring DFSP vs DFSP without recurrences did not yield any significant difference. At follow-up (range: 11-108 months) all patients were alive and well. These findings support the assumption that DFSP originates from primitive mesenchymal cells that are able to show, at least, F and F-MFH differentiation, and corroborate the low-grade malignancy of DFSP regardless of their macroscopic, histologic and ultrastructural characteristics. PMID- 1754507 TI - Paragangliomas of the head and neck. Immunohistochemical analysis of 16 cases in comparison with neuro-endocrine carcinomas. AB - Sixteen cases of paragangliomas of the head and neck including 8 of the vagal body, 3 of the carotid body, 2 jugulotympanic, 2 vagal or jugulotympanic and 1 of the larynx were analysed. Clinically, 13 tumors were benign, 2 showed local aggressivity and 1 showed metastases. All tumors were tested with antisera directed against neuron-specific enolase (NSE), chromogranin A (CGA), S-100 protein, neurofilaments (NF), glial fibrillary acid protein (GFAP) and cytokeratin (CK). Immunohistochemical results were compared with those of 5 cases of neuroendocrine carcinoma (NC) (1 of the oral vestibule, 1 of the larynx, 1 Merkel-cell tumor of the skin and 2 medullary thyroid carcinomas). Immunoreactivity for NSE and/or CGA was always positive in all paragangliomas and NC. S-100 protein was positive in sustenticular cells in all cases of paragangliomas and focally in two cases of NC. NF and GFAP were focally positive in 3 and 2 paragangliomas respectively; and in 1 NC. CK was constantly negative in all cases of paraganglioma and constantly positive in all cases of NC. Antibody anti-CK is the single most useful immunomarker for differential diagnosis between paraganglioma, frequently benign neoplasms and NC commonly aggressive in the head and neck. These findings are consistent with the current concepts of the neuroendocrine system. PMID- 1754508 TI - Rapid supplementary fixation in frozen sections: microwave versus conventional fixation. A double-blind comparative study. AB - The preservation of morphological details in frozen sections subjected to microwave-assisted fixation was compared with that in frozen sections subjected to snap fixation with either formalin/ethanol or ethanol alone. Especially nuclear details were better preserved after short microwave fixation. Ethanol alone gave the poorest results, with loss of nuclear details in the majority of the cases. In this study there was no significant difference between the morphological results obtained with a cheap domestic oven and that with a specialized microwave processor. Microwave-assisted fixation in frozen sections is a simple, rapid method. It is recommended for use in routine laboratories. PMID- 1754509 TI - Classical and chondroid chordoma. A light-microscopic, histochemical, ultrastructural and immunohistochemical analysis of the various cell types. AB - The aim of the present investigation was to characterize the various cell types of classical and chondroid chordomas. Eight cases of classical chordoma, 1 case of sacrococcygeal chordoma with chondroid areas and 2 cases of spheno-occipital chondroid chordoma were studied. Ultrastructurally and immunohistochemically (immunoreactivity for cytokeratins, epithelial membrane antigen [EMA], tissue polypeptide antigen [TPA] and human milk fat globule protein [HMFG]) the 3 cell types (physaliferous, epithelial-like, and spindle-shaped) recognized light microscopically presented features of epithelial differentiation and rather formed a continuous spectrum than being distinct cell types. The chondroid areas of the chondroid chordomas had similar ultrastructural and immunohistochemical properties except for the lack of immunoreactivity for EMA and HMFG. The results of the critical electrolyte concentration technique according to Scott and Dorling indicated that there was no difference in the sulfated glycosaminoglycan content between classical and chondroid chordomas: all the tumors contained chondroitin sulfate. The presence of chondroitin sulfate, immunoreactivity for vimentin and S-100 protein and areas of cartilaginous differentiation in three cases indicate a relationship both to chondromatous tumors and to normal notochord, from which chordoma is believed to originate. PMID- 1754510 TI - Immuno- and enzymehistochemical characterization of 'plasmacytoid T-cells' in formalin-fixed paraffin-embedded tissue of reactive lymph nodes. AB - In eight (10.4%) of 77 randomly selected cases of lymphadenitis, foci of 'plasmacytoid T-cells' (PTCs) were found. We characterized the PTCs in formalin fixed paraffin-embedded tissue by immuno- and enzymehistochemical techniques. In each case the PTCs formed nodular and patchy infiltration patterns around the high endothelial venules in the paracortex of the lymph nodes. The PTCs in half of the cases were present near the intermediary peritrabecular sinuses. The PTCs were found to be positive for CD 45 (LCA), CD 45 R (4 KB 5) and CD 43 (MT 1), but not for CD 45 RO (UCHL 1), L 26 (CD 20), myeloperoxidase, naphthol AS-D chloroacetate esterase, Mac 387, alpha-1-antichymotrypsin or S 100 protein and anti-dendritic reticulum cell antibody. Some lysozyme+ PTCs were mingled in and around the foci in each case. In five cases the PTCs showed weaker positive reactions for CD 68 (EBM 11) and HLA-DR than for T-zone macrophages and sinus histiocytes. Related to the degree of desintegration of the nodular PTC-foci increasing numbers of T- and B-lymphocytes, T-zone macrophages and interdigitating reticulum cells with HLA-DR were detected in the foci. In two cases, where there was no HLA-DR expression by PTCs, small amounts of HLA-DR in secondary lymph follicles and a decrease of HLA-DR+ T-zone macrophages and interdigitating reticulum cells were observed. Our results suggest that there is a high degree of interaction between PTCs and other cellular components in the lymph node. The PTC may represent a special type of resident macrophage with secretory capacities. PMID- 1754511 TI - Atypical bronchial carcinoids lack S-100 positive sustentacular cells. PMID- 1754512 TI - Capillaries within human skeletal muscle fibers. AB - Internalized capillaries, i.e. capillaries within muscle fibers, represent a rare myopathological feature. This was systematically studied in 923 muscle biopsy specimens and found in 24, chiefly in the gastrocnemius muscle, more rarely in the biceps and quadriceps muscles affecting males more often than females and most frequently associated with juvenile spinal muscular atrophy or Becker's muscular dystrophy. Internalized capillaries, often multiple, ran along the long axis of the muscle fiber within an "internalized" extracellular space and were almost exclusively seen in type I myofibers. Internalization seems to start at the site of fiber splitting while penetration through the intact sarcolemma and invasion into transverse tubules were never observed. The presence of internalized capillaries within type I myofibers and increased density of intramuscular capillaries/fiber though not per muscle fiber area suggested hypoxia to play a possible if not crucial role in the formation of internalized capillaries. Our findings do not distinguish between active proliferation of capillaries into myofibers at the site of myofibers and internalization by fusion of vicinal myofibers as the morphogenetic principles suggest that both of these mechanisms may occur. PMID- 1754513 TI - Immunohistochemical and biochemical characterization of the mucin-type tumor associated antigen TAG-12 by monoclonal antibody 7A9. AB - The reactivity of monoclonal antibody 7A9 with normal and neoplastic human tissues and some biochemical characteristics of the antigen (TAG-12) bound by 7A9 were evaluated. Antibody 7A9 showed broad reactivity with various carcinomas in paraffin sections. High percentages of positive tumor cells, displaying membrane and cytoplasmic staining, were noticed in adenocarcinomas of the breast (83/85), serous cystadenocarcinomas of the ovary (15/16), and lung adenocarcinomas (14/16). TAG-12 antigen was also detectable in normal adult and fetal tissues, but the reactivity of 7A9 was mainly restricted to the luminal surface of epithelial cells. For biochemical analyses, TAG-12 antigen purified from T47-D breast carcinoma cells by lectin affinity chromatography was treated with different glycosidases and proteases and analyzed by immunoblotting with 7A9. The data indicate that the antigen recognized by 7A9 is a heavily sialated mucin-type glycoprotein with a molecular weight of more than 200 KD. Similar to all other antibodies against tumor associated antigens, monoclonal antibody 7A9 is not tumor-specific but displays tissue staining patterns with a high carcinoma-to normal ratio. The strong reactivity with the majority of tumor cells in several carcinoma types suggests that 7A9 is useful for in vitro and in vivo targeting of those tumors. PMID- 1754514 TI - What's new in cytostatic drug resistance and pathology. AB - A major problem in cytostatic treatment of malignant tumors is the development of chemoresistant cell clones. An increased understanding of chemoresistance related mechanisms, improved methods for the detection and localization of resistant cell populations including predictive conclusions on the effectiveness of cytostatic drugs would contribute to the advancement of anti-tumor strategies. This paper reviews current concepts suggested for the development of cellular resistance to natural product drugs (anthracyclines, Vinca alkaloids, epipodophyllotoxines, antibiotics; so-called multidrug resistance substances), alkylating agents (nitrosureas, busulfan and mitomycin C), heavy metal compounds (cisplatin) and antifolates (5-fluorouracil, methotrexate) and describes the role of drug transporting and binding proteins (P-170-glycoprotein), detoxifying enzymes (glutathion-S-transferase, dihydrofolate reductase), DNA repair enzymes (topoisomerase I and II, polymerase alpha and beta), and genomic alterations (amplification, double minutes and homogeneous staining regions) due to resistance. It is focussed on the employment of morphological methods (light microscopy, immunocytochemistry, electron microscopy, fluorescence analysis, in situ hybridization, computer aided morphometric analysis) which will help to detect resistant cell clones in tumor biopsies. First correlations between histological data and clinical course will be reported. In the future, the morphological determination of chemoresistance may play an important role in applied functional tumor pathology. PMID- 1754515 TI - Pulmonary myofibroblastic nodules with "amianthoid features". AB - Two consecutive publications appeared 1989 in the same number of a medical journal, which reported peculiar spindle-cell tumors with dense collagen or hyaline nodules, exclusively in inguinal lymph nodes of adults. The first series of 22 cases bore the title "Palisaded myofibroblastoma, a benign mesenchymal tumor of lymph node", the second with 6 identical cases "Intranodal hemorrhagic spindle-cell tumor with "amianthoid" fibers". The following case report deals with a similar tumorous lesion, with multiple small pulmonary nodules, without recognizable lymph node constituents. PMID- 1754516 TI - Localization of elastase and tumor necrosis factor alpha mRNA by non-radioactive in situ hybridization in cultures of alveolar macrophages. AB - Digoxigenin is a new tool for labeling probes which can be detected with the help of specific antibodies in the cell by indirect or direct immunostaining. In contrast to the biotin-reaction, the advantage of digoxigenin is that it does not appear in animal or human cells in nature. In comparison to radioactive labeling methods it is favorable in terms of short exposure time and precise localization of signals in the cell. In this paper we describe the localization of elastase and tumor necrosis factor alpha (TNF alpha) mRNA by non-radioactive in situ hybridization of rat alveolar macrophages in cell culture after stimulation with welder steam dusts. Using digoxigenin labeled probes the determination of specific mRNA's expression and their precise localization in the cytoplasm of the cell could be achieved within one day. PMID- 1754517 TI - Growth hormone receptor expression in the Dunning R 3327 prostatic carcinoma of the rat. AB - The Dunning R3327 rat carcinoma is an important model for human prostate adenocarcinoma. In the present study this tumor was further characterized by immunohistochemical demonstration of receptors for growth hormone (GH-R). Weak GH R immunoreactivity was present in the secretory epithelial cells of the tumor acini. Large epithelial cells which were localized at the periphery of the acini and large cells in the stroma, which are probably derived from the epithelium ("Large neoplastic epithelial cells"), displayed a strong staining with one of the monoclonal antibodies (Mab 263) to GH-R. The presence of GH-R receptors in proliferating prostatic tumor cells supports the concept that GH reacts directly on prostate target tissue to facilitate tumor cell growth. PMID- 1754518 TI - Morphometric and stereological analysis of the effects of 17 beta-estradiol on the glandular epithelium of the castrated guinea pig lateral prostate. AB - Upon administration of pharmacological doses of estradiol to castrated guinea pigs, the secretory cells of the lateral prostate underwent hypertrophy which resulted from significant increases in nuclear and cytoplasmic volume. There were quantitative increases in the small highly electron-dense granules and multivesicular bodies when compared with the castrated control. The dramatic increase in the number of highly electron-dense granules probably occurred at the expense of the low electron-dense granules. The average size of the condensing granules and mitochondria decreased significantly after estradiol administration. However, significant increase in the number of mitochondria was detected when compared with the castrated control. Ultrastructural data revealed no significant changes in the absolute dimensions of granular endoplasmic reticulum or of the Golgi complex, suggesting that estradiol exerted no significant stimulatory effects on these organelles. Pharmacological doses of estrogen appear to regulate the expression of secretory granules and multivesicular bodies in the lateral prostate of castrated guinea pigs. PMID- 1754519 TI - Effect of glycine on retroperitoneal and intraperitoneal organs in the rat model. AB - Twenty Sprague Dawley rats were administered various doses of 1.5% amino acetic acid (glycine), lactated Ringer's, and water, both intravenously and retroperitoneally, in an attempt to recreate the post-transurethral resection syndrome in a rat model. The kidneys, liver, and pancreas were harvested 6 hours after exposure and examined pathologically. Water and lactated Ringer's had no histologic effect on these organs. Glycine was found to have a toxic effect on the kidneys and liver and this effect was dose related. Based on these results, it is postulated that glycine toxicity may play a significant role as a causative factor in producing the post-transurethral resection syndrome. PMID- 1754520 TI - Current views on aetiology and management of haemolytic uraemic syndrome. PMID- 1754521 TI - Secretion of drugs into the human female genital tract. PMID- 1754522 TI - Problems in diagnosis and management of hypertrophic cardiomyopathy. PMID- 1754524 TI - Medical disorders in Alzheimer's disease and vascular dementia. AB - The clinical and postmortem findings of 29 patients with Alzheimer's disease were evaluated and compared to the findings of 19 patients with vascular dementia. The patients with Alzheimer's disease had received treatment for an average of 2.0 internal medical disorders, the patients with vascular dementia for 2.1 disorders. The average number of medical diseases found at postmortem was 3.7 in the group with Alzheimer's dementia and 4.1 in vascular dementia. Apart from a marginally increased rate of peripheral occlusive artery disease in vascular dementia, the proportions of the most common disorders of the cardiovascular, genitourinary, gastrointestinal and endocrinological disorders and the most common causes of death did not differ significantly between these groups. Therefore patients with Alzheimer's disease should receive the same internal medical attention as patients with vascular dementia. PMID- 1754525 TI - Patent foramina ovale in elderly stroke patients. AB - Fifty elderly patients who had suffered cerebrovascular incidents from no obvious cause and 33 age-matched controls were investigated for the presence of a patent foramen ovale by contrast 2-dimensional echocardiography at rest and after the Valsalva manoeuvre. Right-to-left shunting was found in only one patient and in none of the controls. This finding is in contradistinction to young adult stroke patients in whom the prevalence of a haemodynamically significant patent foramina ovale is high. Paradoxical embolism is an uncommon cause of stroke in the elderly. PMID- 1754523 TI - Hepatology. PMID- 1754526 TI - T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa. AB - Endobronchial and nasal mucosa biopsies were obtained from 5 patients with clinically-stable, diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. The distribution of immunocompetent cells within the nasal biopsies of the asthmatic patients reflected a very similar inflammatory infiltrate to that seen in the bronchial biopsies. Significantly raised numbers of T lymphocytes, CD45RO + lymphocytes, RFD1 + macrophage-like cells and RFD7 + macrophages were seen in both the nasal mucosa and the bronchial biopsies. Increases in HLA-DR expression were also seen in the nasal mucosa biopsies from asthmatics although the increases over normal did not reach statistical significance. It is concluded that inflammation present in the nasal mucosa of asymptomatic asthmatics exhibits cellular characteristics also seen in endobronchial biopsies. This observation offers the possibility that mucosal biopsy may be an alternative and less invasive approach for studying the cells involved in the bronchial inflammatory reaction that possibly predisposes asthmatics to bronchial hyper-responsiveness. PMID- 1754527 TI - Dose response to inhaled salbutamol in chronic obstructive airways disease. AB - High dose inhaled salbutamol is increasingly used in the management of chronic obstructive airways disease. To determine the range of doses to achieve optimal bronchodilatation and the proportion of patients requiring high dose therapy we have studied 23 patients with chronic obstructive airways disease. Cumulative dose responses were measured to six incremental doses of salbutamol (0.2 to 1.2 mg) delivered by metered dose inhaler. Results were analysed by polynomial regression to calculate the smallest dose required to produce 90% maximal bronchodilatation in each patient. While 5/23 (22%) required greater than 1 mg the majority, 14/23 (61%), achieved 90% maximal bronchodilation with salbutamol 0.6 mg or less. The 8 patients with severe airflow limitation (FEV1 less than or equal to 1 litre) showed a similar pattern of response. We conclude that in chronic obstructive airways disease there are wide individual variations in the dose of inhaled salbutamol producing 90% maximal bronchodilatation with only a minority requiring high dose therapy. PMID- 1754528 TI - Small bowel function after aortic surgery. AB - One cause of post-operative morbidity in the elective repair of abdominal aortic aneurysms is the development of a paralytic or 'adynamic' ileus. In a series of 20 consecutive patients undergoing such a procedure, the maintenance of small bowel motility and absorptive capacity in the immediate post-operative period was assessed using barium sulphate and xylose passed down a naso-duodenal tube sited at the time of surgery. This simple study demonstrated that small bowel function was preserved in all cases, and hence that patients could be fed enterally via naso-duodenal tube (in particular using very low residue formulae) rather than using costly parenteral regimens, should an ileus persist. PMID- 1754529 TI - Clustering of colorectal neoplasia: characteristics of coexisting adenomas in patients with severely dysplastic polyps or invasive (malignant) polyps as compared to patients with benign adenomas or carcinomas. AB - This study compared the size, histology and morphology of coexisting neoplastic polyps found in colonoscopy, and evaluated the clustering of these polyps in patients with either colorectal carcinoma, cancerous polyps or benign adenomas. Patients were divided by their most malignant form of neoplasia: Group A included 58 patients with early invasive cancerous polyps, and Group B included 73 patients with in situ carcinoma within an adenoma. Group C consisted of 335 patients with benign adenomas, and Group D had 289 patients with colorectal carcinoma. There were no significant differences between the four groups regarding sex, age and ethnicity. The cancerous polyps were significantly larger than the benign polyps. There were significantly (P less than 0.01) more patients with multiple (greater than or equal to 5) colonic lesions in Groups A or B than in Groups C or D. Coexisting polyps were much closer to the index growth, and demonstrated more severe dysplastic changes in the case of cancerous polyps than those associated with benign polyps or cancer. Based on our data we speculate that cancerous polyps are not merely a middle link in adenoma-carcinoma sequence, but rather mark a subset of patients who are especially prone to develop neoplastic changes in their colonic mucosa. These patients should be included in a more strict colonoscopic surveillance programme. PMID- 1754530 TI - Syringomyelia associated with post-meningitic spinal arachnoiditis due to Candida tropicalis. AB - A 63 year old man who suffered from syringomyelia related to post-meningitic spinal arachnoiditis caused by Candida tropicalis is reported. The clinical syndrome of syringomyelia developed gradually and a definite diagnosis was delayed for more than 10 years. The patient has partially recovered after surgical treatment. This form of fungal infection and its delayed neurological complication in the form of syringomyelia has not been reported previously, to our knowledge. PMID- 1754531 TI - Life-threatening hypercalcaemia in association with Addisonian crisis. AB - A 35 year old woman was admitted with acute radial artery occlusion necessitating two operations and thrombolytic therapy. Subsequently a diagnosis of primary hypothyroidism was made and she was commenced on thyroxine replacement therapy. Her condition, however, continued to deteriorate with the development of an Addisonian crisis heralded by, and complicated by, severe, life-threatening hypercalcaemia. This case highlights the importance of considering Addison's disease in any patient whose condition deteriorates after the introduction of thyroxine replacement, and illustrates the often forgotten association of hypercalcaemia and hypoadrenalism. PMID- 1754532 TI - Diverticulum of the rectum due to a rectal leiomyosarcoma. AB - A 78 year old woman with a rectal leiomyosarcoma is presented. The case is of interest because of very unusual radiological and operative features of a large rectal diverticulum. As a result of the difficulty in making the correct diagnosis pre- or intraoperatively, a simple, but possibly suboptimal, resection was performed. Although the patient has done well, the long-term outlook is uncertain. The problems of optimum management and prediction of outcome in this uncommon condition are discussed. PMID- 1754533 TI - Strangulated femoral hernia: the clinical trap. PMID- 1754534 TI - Fenfluramine--induced irreversible pulmonary hypertension. PMID- 1754535 TI - Bone lesions in chronic granulocytic leukaemia. PMID- 1754536 TI - Salmonella enteritidis empyema complicating lupus pleuritis. PMID- 1754537 TI - Spontaneous oesophageal haematoma presenting as acute myocardial infarction: implications for thrombolytic therapy. PMID- 1754538 TI - Genetic variation in the incidence of pipped eggs in turkeys selected for low and high semen ejaculate volume. AB - Genetic variation in embryonic mortality, expressed as embryos that pip their eggshell but do not hatch, was investigated in turkeys selected for low and high semen ejaculate volume (SEV). Through five generations (Generations 10 to 14, inclusive) mean heritability estimates for pipped eggs were .21 and .08 in the low- and high-SEV lines, respectively. Estimates of sire, dam, and within-hatch components of variance suggest greater environmental and maternal effects than genetic influences on the incidence of pipped eggs in turkeys. PMID- 1754539 TI - Body weight and carcass development in different lines of turkeys. AB - Body weight and carcass component weights of turkeys from a growth-selected line (F), a randombred control population (RBC2), and a commercial sire line (C) were compared at hatch, 4, 8, 12, and 16 wk of age. At hatch there were no significant differences in BW between the F and RBC2 lines, but the C line poults weighed significantly less than the F line poults. Total Pectoralis muscle weight of the F line was larger than for Lines C and RBC2 at hatch, but there were no line differences in drum weight or length. The F line was still heavier than the other lines at 4, 8, and 12 wk, but the absolute and relative weights of the Pectoralis major (P. major) muscle were larger in the C line than the other lines at all ages. Selection for BW increased the weight of the P. major in the F line compared with the RBC2, but differences in the relative weight of the muscle were not consistent. The large line differences for the absolute and relative weight of the P. major were not observed for the Pectoralis minor. At all ages, the lengths of the tibia and femur were greater in the F line than the other lines. At 4 and 8 wk, bone length in the C line was greater than the RBC2, but at 12 and 16 wk there were no significant differences between these lines. The fast-growing F and C lines had more abdominal fat than the RBC2 at 16 wk of age. PMID- 1754540 TI - Effect of floor type and energy source on growth and productivity of broiler breeders. AB - Arbor Acres broiler breeder chicks were raised through an egg production cycle on either wood or plastic slats and either full- or partial-slat flooring. Two diets with either corn starch (CHO) or fat (FAT) as the primary energy source were fed at a rate consistent with the breeder's recommendations to examine the effect of energy source on fat deposition and productivity. Fertility and hatchability were unaffected by slat material or floor type. Mean hen-day egg production and floor egg production were significantly (P less than .05) reduced for birds on full slat floors. In addition, birds on full-slat, plastic floors averaged 6.4% fewer eggs over the production cycle versus birds on full-slat, wood floors. Floor egg recovery from full-slat floors was not considered to be the major reason for this reduced egg production. Wood or plastic slats had no effect on average egg production for birds on partial-slat and litter floors. Energy source had no effect on growth or productivity except during Weeks 17 and 18 of production when birds fed the FAT diet had a greater egg production than birds fed the CHO diet. Overall mean hen-day egg production, fertility, and hatchability were unaffected by dietary energy source. Abdominal fat pad weight and adipocyte characteristics were also similar for FAT- and CHO-fed birds. PMID- 1754541 TI - Effect of roost temperature on performance of chickens in hot ambient environments. AB - A split-plot experiment was conducted in thermally controlled chambers using Columbian Plymouth Rock chickens to determine the effect of water-cooled roosts on performance in hot ambient conditions. The birds were subjected to 25 +/- 1, 35 +/- 1, and 25 +/- 1 C ambient temperature treatments for 2, 3, and 2 wk, respectively. Roost temperature treatments were either cool (20 +/- 1 C) or air equilibrated (25 +/- 1 or 35 +/- 1 C). The performance parameters evaluated were percentage hen-day egg production, egg weight, feed intake, feed conversion, fertility, and hatchability. Birds subjected to the water-cooled roost treatment had consistently higher performance than birds using the air-equilibrated roost under all three ambient temperatures. Both ambient and roost temperature treatments significantly influenced percentage hen-day egg production, average daily feed intake, and percentage hatchability (P less than or equal to .05). However, the biggest differences in performance were observed during the heat stress period. Decreases in performance during the heat-stress period from the thermoneutral control values were: 5.95 and 13.1 percentage points for hen-day egg production, 22.2 and 34.8 percentage points for average daily feed intake, and 5.17 and 15.38 percentage points for hatchability in water-cooled and air equilibrated roost treatments, respectively. The ambient and roost temperature treatments did not significantly affect egg weight, feed conversion, or percentage fertility. The improved performance with water-cooled over air equilibrated roost treatments, especially during heat-stress periods, indicates that the water-cooled roosts minimized the deleterious effects of heat stress through conductive heat loss from the birds to the roost. PMID- 1754542 TI - The fate of Pasteurella multocida after intratracheal inoculation into turkeys. AB - Young adult turkeys were intratracheally inoculated with the P-1059 strain of Pasteurella multocida, and the fate of the organism was studied by quantifying the organism in various respiratory and systemic tissues at various times after the inoculation. The results showed that, in the first 2 h, on the order of 10(8) to 10(9) organisms deposited at the upper trachea multiplied in situ to gradually spread downwards to the lower respiratory tract. In the majority of turkeys, by 6 h postinoculation the organism invaded the circulatory system and multiplied vigorously in the liver and spleen. In some birds, however, the organism appeared to have reached the liver from the trachea instantaneously by an unidentified mechanism. Vaccination with inactivated vaccines protected turkeys from intratracheal challenge exposure, as well as from intramuscular inoculation. PMID- 1754543 TI - Methods for inoculation and recovery of Salmonella from chicken eggs. AB - Various methods of applying inoculum and recovering low numbers of artificially inoculated Salmonella typhimurium on eggs were evaluated. Inoculation methods tested were suspending cells in 1) .85% saline; 2) 1% peptone; 3) sterile chicken fecal paste; or 4) a 1:10 dilution of chicken feces in .85% saline. Sampling methods tested were 1) shell and membrane massage; and 2) mortar and pestle grinding of shells and membranes. The method that yielded the best recovery of low numbers of Salmonella was as follows: 1) apply cell suspension in 1% peptone to egg; 2) sample egg by a hand crush and massage of shell and membranes in 50 mL of buffered peptone; 3) incubate shell and membranes in buffered peptone overnight and then plate onto selective agar. Methods that did not improve sensitivity of recovery included varying the inoculum drying time, addition of FeSO4 or Cleland's reagent to the recovery medium, and varying the temperature of the inoculum to affect penetration. PMID- 1754544 TI - High dietary fat increases toxicity of diacetoxyscirpenol in chickens. AB - The influence of high dietary fat on the toxicity of diacetoxyscirpenol (DAS) was investigated in a 2 x 5 factorial arrangement of treatments (6 and 12% fat, and 0, 1, 2, 4, and 8 micrograms DAS/g diet). The 3-wk body weight was decreased (P less than .0001) by DAS, but fat had no significant (P less than .05) effect. There was a highly significant (P less than .0059) interaction manifested at the higher levels of DAS by a greater decrease in body weight in the high-fat diet than in the low-fat diet. Neither feed conversion nor percentage of fat in fecal material were affected significantly (P less than .05) by DAS. These data were consistent with the high-fat diet promoting lipid micellar absorption of DAS and with DAS, once absorbed, inhibiting protein synthesis at the ribosomal level, a well established mechanism of action for trichothecene toxins such as DAS. PMID- 1754545 TI - Measurement of malabsorption of carotenoids in chickens with pale-bird syndrome. AB - Because pale-bird syndrome (PBS), defined as the failure of birds to realize the color potential of their diet, has been demonstrated to be caused by malabsorption or by hyperexcretion of carotenoids, a method for measuring malabsorption of carotenoids would be useful. The absorption of dietary canthaxanthin, a red diketocarotenoid, into serum during aflatoxicosis was measured in an experiment with a 2 x 9 factorial arrangement of treatments (0 and 5 micrograms of aflatoxin/g of diet; serum collected at 0, 2, 4, 6, 8, 10, 12, 14, and 24 h after a standard meal fed to four groups of 10 3-wk-old birds). Serum canthaxanthin levels determined by HPLC attained plateau values between 8 and 14 h after the meal. The absorption of canthaxanthin was depressed significantly (P less than .05) in birds with aflatoxicosis from 4 to 24 h after feeding the standard meal. Four field flocks diagnosed as having PBS were tested for malabsorption by intubating 10 birds with a standard amount of canthaxanthin and measuring serum canthaxanthin 12 h later. One flock had about 85% normally pigmented birds and 15% extremely pale birds, the second flock had a coccidiosis history, the third had a Newcastle disease history, and the fourth had a history of both coccidiosis and Newcastle disease. The flocks were 5- to 6-wk-old, received feed of the same manufacture, and their disease outbreaks had occurred 2 wk earlier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754546 TI - Uterine calcium-binding protein activity of nonlaying hens and hens laying hard shelled or shell-less eggs. AB - Uterine calcium-binding protein (CaBP) activity was compared at oviposition and 14 h postoviposition in nonlaying (NL) hens and hens laying a high incidence of shell-less (SL) or hard-shelled (HS) eggs fed a commercial laying diet. Epithelial cells were removed from uteri of NL, SL, and HS hens and homogenized in Tris buffer, pH 7.4. Proteins in homogenate were fractionated by the addition of ammonium sulfate and centrifugation, separated by Sephadex chromatography, and measured by ultraviolet spectrophotometry at A280. Calcium-binding protein activity was determined using a 45Ca-chelex binding assay. Two peaks of CaBP activity were detected and designated CaBP-a (28,000 Da) and CaBP-b (16,000 Da). Uterine CaBP-b may differ from CaBP-a only in Ca content. The activities of CaBP (a and b) were higher (P less than or equal to .05) in HS and SL hens than in NL hens at 0 h. There was no significant difference (0 h) between CaBP activity (a versus b) of either HS or SL hens. There was also no difference (0 h) of CaBP-a or CaBP-b activity when SL and HS hens were compared. Uterine CaBP-a activity was lower (P less than or equal to .05) in SL hens than HS hens at 14 h. Under normal dietary conditions, the level of CaBP activity at 14 h may be associated with SL egg production. PMID- 1754547 TI - Influence of orotic acid on performance, liver lipid content, and egg cholesterol level of laying hens. AB - Three experiments were conducted to determine the effects of dietary orotic acid (OA) on laying hen performance, liver lipid content, and plasma and egg cholesterol levels. Laying hens were fed a basal diet supplemented with 0, .5, 1.0, and 2.0% OA for 8 wk. Performance of the hens and cholesterol levels were measured at biweekly intervals. In all three experiments, OA decreased (P less than .05) BW in a linear manner. In two experiments, OA caused a linear decrease in total liver lipid (P less than .05), and in a third experiment OA resulted in a quadratic effect (P less than .01) on liver lipid content. There were no effects observed by OA supplementation on egg weight, yolk weight, percentage yolk, or egg production. Orotic acid failed to influence egg cholesterol content in any of the biweekly measurements of the three experiments. In two experiments, total plasma cholesterol content was not influenced by OA supplementation. Orotic acid significantly reduced (P less than .05) free and total plasma cholesterol in a third experiment when measured at Weeks 4, 6, and 8 of the experiment. The data indicate that OA is an ineffective dietary supplement for reducing egg cholesterol levels in laying hens. PMID- 1754548 TI - Plasma progesterone, luteinizing hormone concentrations, and granulosa cell responsiveness in heat-stressed hens. AB - Plasma progesterone and luteinizing hormone (LH) profiles were obtained during the first ovulatory cycle of heat-stressed (HS, 35 C; n = 24) and unstressed (US, 17 to 27 C; n = 24) hens using 30-min sampling intervals beginning approximately 6 h prior to ovulation. Progesterone levels from HS hens were lower from 6 h [.07 +/- .01 (SE) versus 1.66 +/- .25 ng/mL; P = .008] to predicted ovulation (.06 +/- .006 versus .70 +/- .18 ng/mL; P = .07). Likewise, LH levels from HS hens were lower from 6 h (1.55 +/- .16 versus 3.86 +/- .34 ng/mL; P = .007) to predicted ovulation (1.63 +/- .18 versus 2.50 +/- .27 ng/mL; P = .01). Eggs from HS hens were more often laid early (less than 24 h) than eggs from US hens (71.42 versus 13.33%, respectively; P = .01), but US hens more often laid eggs of a normal oviposition interval length (24 to 26 h) compared with HS hens (73.34 versus 14.29%; P = .0005). The percentage of delayed eggs (greater than 26 h) was not different (US, 14.29 versus HS, 13.37%; P = .75) between the two treatment groups. Basal production of progesterone by dispersed granulosa cells from US hens was 97.62 +/- 16.01 ng/mL. Challenge by LH increased this to 417.50 +/- 53.38 ng/mL (P = .0001). In contrast, basal progesterone secretion by cells from HS hens was 40.25 +/- 6.60 ng/mL (P = .0001) and LH challenge failed to increase progesterone production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754549 TI - Efficacy of lateral ventricular injection of epinephrine, cyproheptadine, or adenosine triphosphate on feed intake in thiamin-deficient turkeys. AB - In previous work, thiamin deficiency (TD) resulted in decreased brain levels of adenosine triphosphate (ATP) and epinephrine, but serotonin (5-HT) was increased in the turkey. The goal of the present study was to determine whether the introduction of calculated levels of epinephrine, ATP, or cyproheptadine into the lateral ventricle could affect feed intake of TD birds. Adenosine triphosphate, epinephrine, and cyproheptadine (5-HT antagonist) were injected into the lateral ventricle of TD and control birds. These injections did not alter feed intake in the control birds. Cyproheptadine and ATP decreased feed intake in the 1st h in the TD birds as compared with sham-injected TD birds (P less than .05), but epinephrine had no effect. The results indicate replacement or inhibition of a single altered neurochemical does not increase short-term feed intake in TD birds. PMID- 1754550 TI - The effect of thiamin deficiency on amino acids in the brain, liver, and plasma of the turkey. AB - The present study was conducted to determine the effect of thiamin deficiency (TD) on amino acids in brain, liver, and plasma. Twenty-seven 1-wk-old female turkeys were assigned to TD or control groups. Experimental birds were fed a TD diet; control birds received the same diet with thiamin at levels recommended by the National Research Council. Chromatographic analysis at 12 days of age found altered levels of amino acids in selected brain areas and liver of TD birds. Proline was increased in the TD archistriatum and liver. Leucine was elevated in the TD hypothalamus, medulla-pons, midbrain thalamus, and cerebellum. Threonine was lower in the hippocampus, but was increased in the liver of TD birds. Glutamine declined in the TD hippocampus, but glutamate increased in the TD liver only. Urea decreased and valine increased in the TD medulla-pons. Aspartic acid and serine decreased in the TD liver. These results indicate that dietary TD does alter amino acids in these tissues. PMID- 1754551 TI - Research note: effects of age and immunization interval on the anamnestic response to T-cell-dependent and T-cell-independent antigens in chickens. AB - Measurement of a humoral anamnestic response is a common procedure used to evaluate immunological competence. The purposes of the present study were to determine the optimum time period between primary and secondary immunizations needed to obtain the maximum antibody titer and to determine whether this interval differs with the age of the chicken or with the type of inducing antigen. The anamnestic responses of birds of two ages to a T-cell-dependent antigen (SRBC) and to a T-cell-independent antigen (Brucella abortus, BA) were evaluated. Birds of 4 wk or 6 mo of age were injected i.v. with either BA or SRBC, and a secondary injection was given 2, 4, 6, or 8 wk later. Agglutination titers for total and mercaptoethanol (ME)-resistant antibodies were determined from serum samples collected at 3, 6, and 9 days postsecondary immunization. Generally, titers were highest at 6 days postsecondary immunization. For both antigens, the chick total antibody levels at Day 6 postsecondary immunization were higher at 4-, 6-, and 8-wk immunization intervals than at 2-wk intervals; adult titers were independent of immunization interval. There was an interaction between age of birds and type of antigen. PMID- 1754552 TI - Research note: evaluation of humoral and delayed hypersensitivity responses in cockerels reared under constant light or a twelve hour light:twelve hour dark photoperiod. AB - Immature cockerels were reared under constant light [24 h light (L):0 h dark (D)] or a 12L:12D photoperiod in order to evaluate the effect of constant light on immunoresponsiveness. At 10 wk of age males were immunized with SRBC, with reimmunization occurring either 3 or 8 wk later. Animals reared under constant light had lower (P less than .05) anti-SRBC antibody titers than the 12L:12D males. Additionally, the pattern of the antibody response following secondary immunizations were different, with 24L:0D males exhibiting no increase in antibody titers between Days 3 and 9 postinjection. Delayed hypersensitivity responses of 24L:0D males were lower (P less than .05) than those of 12- or 16-wk old 12L:12D males. Taken together, these results suggest that circadian light:dark cycles may play a role in modulating the immune system. PMID- 1754553 TI - Research note: lack of an effect of high levels of menadione on tumor development in Japanese quail females. AB - The objective of the experiment was to study the influence of a high but nontoxic dietary level of menadione (vitamin K3) on the incidence of leiomyomas and leiomyosarcomas in the oviduct of females from various lines of Japanese quail. Analyzed values of vitamin K3 per 1,000 kg of feed were 7.37 g in the control diet, and 149.6, 1,722, and 3,722 g for the experimental diets from 0 to 4, 5 to 8, and after 8 wk of age, respectively. Females were killed after they had been in production for 158 days. Females from three large-bodied lines had a greater incidence of smooth muscle tumors than those from a smaller randombred control line. The high dietary level of vitamin K3 had no influence on tumor development. PMID- 1754554 TI - False-negative prenatal exclusion of Wiskott-Aldrich syndrome by measurement of fetal platelet count and size. AB - The study of the fetal platelet count and size can, according to the literature, be used for the prenatal diagnosis of the Wiskott-Aldrich syndrome (WAS). So far, no affected fetuses have been identified by this method. All pregnancies in which this method had been applied to resulted, as correctly predicted, in the birth of normal children. Here we report on a familial case of WAS where the haematological parameters failed to reveal the affected second child. Hence we assume that the platelet count and size of platelets remain normal in fetuses with WAS to the gestational age of 22 weeks and cannot be used for prenatal diagnosis. PMID- 1754555 TI - Clinical and pathological factors in spontaneous abortion following chorionic villus sampling. AB - Twenty-nine cases of spontaneous abortion following first-trimester chorionic villus sampling (CVS) were reviewed out of a series of 722 patients. Of the 29 cases, there were only four abnormal CVS results. Pathological examination was performed in 79 per cent of cases, and this did not identify any characteristic pathological feature associated with spontaneous abortion after CVS. There was no obvious difference in the pathological features following the transabdominal (TA) or the transcervical (TC) methods. The majority of miscarriages occurred within 4 weeks of the procedure, but 38 per cent of cases aborted between 7 and 14 weeks after CVS. The TC method was used in 22 patients; the TA in 6; and both methods in 1 patient. The TA method was associated with a significantly lower fetal loss rate than the TC method (TA 2 per cent, TC 9 per cent, p less than 0.001). PMID- 1754556 TI - Prenatal diagnosis of PIBIDS. AB - In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6-12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2-13.5 per cent of residual activity. PMID- 1754557 TI - Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q41) AB - Many authors have suggested that individuals affected by a terminal 1q deletion display a phenotypically definable and recognizable syndrome. In all of the 27 cases reported to date, the breakpoints were at band q42 or distally to it. To our knowledge, we report the first case of a terminal 1q41 deletion. Diagnosis was made prenatally by amniocentesis, following ultrasonographic diagnosis of omphalocele, cerebral ventriculomegaly, and increased nuchal fold thickness in a 19-week female fetus. Multiple facial and extremity features were consistent with the proposed distal 1q deletion syndrome; omphalocele, however, has not been reported previously. The absence of liver herniation into the omphalocele sac in this case supports the previously reported association of this finding with chromosomal anomalies. PMID- 1754558 TI - A case of mosaicism involving an unstable 13/14 Robertsonian translocation. AB - Prenatal diagnosis of mosaicism involving an apparently unstable 13/14 Robertsonian translocation is reported. This illustrates the difficulties encountered in counselling when mosaicism is ascertained prenatally. Other reported examples of apparently unstable Robertsonian translocations are discussed. PMID- 1754559 TI - Trisomy 12 mosaicism. PMID- 1754560 TI - A normal 46,XX infant with a 46,XX/69,XXY placenta: a major contribution to the placenta is from a resorbed twin. AB - A predominantly triploid 69,XXY placenta was found associated with a normal 46,XX infant. Therefore, a triploid placenta is apparently capable of supporting normal fetal development. The chromosome and pathological results support the conclusion that the triploid placenta originates from a 'vanishing twin' pregnancy. This case is unusual in that persistence of the placenta from the vanished twin has virtually replaced most of the normal placenta. PMID- 1754561 TI - Prenatal diagnosis of harlequin ichthyosis by fetal skin biopsy; report of two cases. AB - Two cases of harlequin ichthyosis were successfully diagnosed prenatally by fetal skin biopsy. The aborted fetuses were later confirmed to be afflicted with this very unusual skin disease. Both families had a previous history of harlequin ichthyosis. In performing the biopsy, it was found that amniotic fluid cytology can also be very helpful in the diagnosis of this kind of severe ichthyosis. With regard to these families, the disease may have been transmitted in an autosomal dominant fashion, and not in a recessive manner as is commonly believed. PMID- 1754562 TI - Early transvaginal sonographic diagnosis of alobar holoprosencephaly. AB - Holoprosencephaly is a cerebral anomaly resulting from incomplete cleavage of the primitive prosencephalon or forebrain. Early detection of this anomaly is very important since the most severe form is incompatible with life. The diagnosis also signals the need for a chromosomal determination since chromosomal abnormalities have been associated with this anomaly. An early diagnosis of alobar holoprosencephaly at 14 weeks' gestation, employing transvaginal sonography, is reported. Our findings are compared with prenatal transabdominal sonographic findings of holoprosencephaly which have been reported during the last decade in the literature. PMID- 1754563 TI - Maternal serum human chorionic gonadotropin levels in twin pregnancies. AB - Introduction of combined screening with maternal serum alpha-fetoprotein and human chorionic gonadotropin (MShCG) assays for fetal chromosome defects requires establishment of the normal range for twins. This report documents that the normal range for MShCG between 15 and 19 weeks in twin gestations was 1.84-2.41 multiples of the singleton median. Of the 192 twin pregnancies studied, 31.7 and 47.9 per cent had MShCG values greater than or equal to 2.5 and greater than or equal to 2.0 multiples of the singleton median, respectively. PMID- 1754564 TI - Prenatal diagnosis for dystrophia myotonica using the polymerase chain reaction. AB - The polymerase chain reaction has been used to detect an abundant class of short repeat DNA families of the form (dC-dA)n.(dG-dT)n, known as microsatellites. These units are found throughout the human genome and have been characterized for several loci including APOC2 on chromosome 19q12-q13.2. The locus APOC2 is linked to the gene for dystrophia myotonica and a microsatellite within this locus was used to derive polymorphisms in a family to predict the inheritance of the disease. Chorionic villus sampling (CVS) was performed at 15 1/2 weeks' gestation. Following DNA extraction from the CVS material and parental blood samples, microsatellite analysis was carried out by the polymerase chain reaction. PMID- 1754565 TI - Post-mortem findings in a fetus with 48,XXY,+21. AB - A fetus with 48,XXY,+21 was detected on routine amniocentesis at 15 weeks for advanced maternal age. Fibroblast cultures from six different tissues were initiated after termination and each showed the same karyotype without any tissue limited mosaicism. The only phenotypic abnormality detected at post-mortem examination was bilateral clinodactyly of the fifth finger which had been detected on ultrasound. The maternal serum alpha-fetoprotein and the femur length were normal. Maternal age remains an essential criterion for prenatal diagnosis. PMID- 1754566 TI - Pallister-Killian syndrome diagnosed by chorionic villus sampling. AB - The first prenatal diagnosis of Pallister-Killian syndrome by chorionic villus sampling is presented. Fetal hydrops was noted on ultrasound in early pregnancy, and the karyotype revealed isochromosome 12p mosaicism. PMID- 1754567 TI - Duplication of chromosome 11 centromere in fetal and maternal karyotypes: a new variant? AB - Fetal chromosome analysis in a 39-year-old mother revealed a chromosome 11 aberration interpreted as a duplication of the centromere. This was also found in the mother's karyotype, raising the possibility that the abnormality was a new variant of no clinical consequence. PMID- 1754568 TI - Prenatal diagnosis of duplication cyst of the pylorus. AB - The first description of the antenatal appearance of a duplication cyst of the pylorus is presented. Prior to the infant's delivery, the possibility that this intra-abdominal cystic mass represented a choledochal cyst was also strongly considered. The antenatal detection of this cystic mass allowed close neonatal surveillance and timely surgical intervention prior to the onset of serious neonatal complications. The embryogenesis of duplication cysts of the gastrointestinal tract and bronchopulmonary foregut malformations is reviewed. The clinical utility of the prenatal diagnosis of such fetal gastrointestinal anomalies is also discussed. PMID- 1754569 TI - A second report of normal outcome with mosaic isochromosome 20q found on amniocentesis. PMID- 1754570 TI - The maternal-fetal electrical potential difference: new findings and a perspective. PMID- 1754571 TI - Syncytiotrophoblast brush border proteins recognized by monoclonal antibody TRA-2 10 and rabbit anti-TLX sera. AB - Different subsets of placental trophoblast epithelium are directly exposed to the maternal immune system during pregnancy and consequently represent major elements in allogeneic interactions. It has been proposed that the trophoblast--lymphocyte cross-reactive (TLX) alloantigen system is involved in maternal allogeneic recognition during pregnancy. Monoclonal antibody TRA-2-10 putatively recognizes TLX antigens, but its reactivity with trophoblast and normal tissues has not been documented in detail. In this report, immunohistological investigations revealed that TRA-2-10 recognizes all subsets of trophoblast in addition to amniotic and seminal vesicle epithelia. Immunoblotting demonstrated reactivity with glycoproteins of 55,000 and 65,000 mol. mass under non-reducing conditions on various cell types. These proteins displayed tissue-specific size variations and individuals varied in the amounts expressed of the two species. On the basis of blocking and immunoprecipitation experiments, TRA-2-10 reactive antigens are recognized by rabbit anti-TLX sera and are potential TLX antigen candidates. However, TLX antigens are found in seminal plasma whilst TRA-2-10 reactive antigens are not. Both TLX and TRA-2-10 antigens appear related if not identical to membrane cofactor protein (MCP) by virtue of shared molecular characteristics and blocking of lymphocyte binding of monoclonals to MCP by polyclonal anti-TLX. Extra-embryonic membranes are thus richly endowed with a complement regulatory protein which could facilitate their roles in protection of the fetus by avoidance of harmful maternal immune response amplification. PMID- 1754572 TI - Expression of HLA class I and beta 2-microglobulin on human choriocarcinoma cell lines: induction of HLA class I by interferon-gamma. AB - The trophoblast cells which contact with maternal tissue express HLA class I either weakly or not at all. This phenomenon is beneficial for the protection of the fetus from immunological rejection by the mother. However, the mechanisms of reduced expression of HLA class I are unexplained. Therefore, we utilized choriocarcinoma cells to analyse the suppressive mechanisms to HLA class I expression in trophoblasts. In this paper we reported the heterogeneity of HLA class I expression in five choriocarcinoma cell lines. The levels of surface HLA class I molecules correlate approximately with mRNA of HLA class I heavy chain, and all choriocarcinoma cells produce moderate amounts of surface and secreted beta 2 microglobulin. It was also found that interferon gamma upregulates HLA class I molecules and mRNA in two choriocarcinoma cell lines, NUC1 and HCCM5. PMID- 1754573 TI - Expression of alkaline phosphatase in differentiated rat labyrinthine trophoblast tissue. AB - In this report, we describe the generation of specific antibodies to rat alkaline phosphatase and the temporal and regional characteristics of alkaline phosphatase expression during maturation of the rat chorioallantoic placenta. An antipeptide antiserum was generated to the amino terminal 15 amino acids of rat alkaline phosphatase. The antiserum specifically recognized alkaline phosphatase. Alkaline phosphatase expression was monitored in the junctional and labyrinth zones of the chorioallantoic placenta by Western and Northern blot analyses. Alkaline phosphatase protein and mRNA were present in both the junctional and labyrinth zones on day 13 of gestation. As gestation advanced, alkaline phosphatase mRNA and protein expression decreased below the limits of detection in the junctional zone, while alkaline phosphatase expression increased in the labyrinth zone. Labyrinthine alkaline phosphatase migrated predominantly as a 95-kDa species, whereas rat kidney expressed exclusively the 75-kDa species. Enzymatic deglycosylation of the 75- and 95-kDa alkaline phosphatase species resulted in the generation of a 55-kDa species. In summary, alkaline phosphatase expression is a useful indicator of trophoblast differentiation. PMID- 1754574 TI - Amitosis and endocycles in early cultured mouse trophoblast. AB - The possible occurrence of amitosis has been studied in nuclei of trophoblast outgrowths of mouse embryos placed in culture at the two-cell stage. By day 7 of culture, the inner cell mass has usually floated away, while the trophoblast outgrowth remains attached. Of 591 trophoblast cells from 25 embryos, 469 were uninucleate, 87 binucleate, 4 trinucleate, and in 31 the nuclei were attached to each other. In our interpretation, these come about through a process in which the nucleus stretches, then the nuclear membrane invaginates and finally constricts the nucleus into two parts. The resulting nuclei, asymmetric in size and in amount and arrangement of heterochromatin and nucleoli, lie side-by-side. We conclude that these cells with two or more attached or separate nuclei represent stages in true amitosis. In Table 1, amitosis is compared with mitosis without cytokinesis and with cell fusion, both of which can also give rise to binucleate and multinucleate cells. Mitosis without cytokinesis does not agree in any respect with the characteristics of amitosis, whereas at least a few similarities exist between cell fusion and amitosis. However, amitosis may give rise to near-haploid nuclei, which cannot be produced by mitosis or cell fusion. Simultaneously with amitosis, the nuclei grow through endocycles. In many nuclei, the heterochromatin is clearly underreplicated, while the nucleoli are numerous and often of enormous size, probably reflecting amplification of the rRNA genes. PMID- 1754575 TI - Development of the early human placenta: a morphometric study. AB - The placentae of 46 normal pregnancies artificially terminated between 6 and 15 weeks of gestation were investigated morphologically to provide trends in early villous development. Study of the specimens included phase contrast microscopic examination and histomorphometric investigation in all cases, and scanning electron microscopy in ten cases. Histomorphometric measurements included the villous barrier thickness i.e. the distance between the intervillous space and the villous capillary lumen, the trophoblastic layer thickness and the volume fraction of each villous constituents, i.e. trophoblast, stroma and capillaries. Significant negative correlations were observed between gestational age and the villous barrier and trophoblastic thickness. The data obtained were separated into two groups, embryonic (5-10 weeks) and fetal (11-15 weeks) groups, and compared. The mean barrier thickness, the mean trophoblastic thickness, the mean volume fraction for trophoblast and the sprouting-villous index were significantly greater during the embryonic period compared with the fetal period. The mean volume fraction for the stroma and for the fetal capillaries, and the mean number of capillary profiles per villous profile were significantly smaller during the embryonic period than during the fetal period. The comparison of placental histomorphometric data obtained in cases of normal early pregnancies with those observed in cases of abnormal early pregnancies could help us to elucidate the origin of anatomical and biological changes in these cases. PMID- 1754576 TI - Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats. AB - In order to find out if inefficient transport of amino acids contributes to a decrease in fetal weight during maternal malnutrition, we injected [14C]- and [3H]-labelled aminoisobutyric acid (AIB), respectively, in the mother and its fetuses and determined its transplacental kinetics on day 20 of gestation in rats fed a 21 per cent (control) or a low (5 per cent) protein diet. Rats fed a low protein diet consumed significantly less food than did the rats fed a control diet and thus suffered from protein-calorie malnutrition. A low protein diet led to a significant (P less than 0.05) decrease in maternal and fetal volume of distribution of AIB, a decrease in the clearance of AIB from the mother to the fetus and an increase in the time required for the fetal plasma AIB concentration following maternal injection to exceed the maternal plasma AIB concentration. The clearance of AIB from the fetus into the mother or to outside (e.g. amniotic fluid) was not altered by protein deficiency. It is concluded that a decrease in the efficiency of the placenta to deliver amino acids to the fetus may be a contributing factor in fetal growth retardation during maternal protein malnutrition. PMID- 1754577 TI - Antibacterial properties of human amniotic membranes. AB - Amniotic membranes are widely used in a multitude of surgical applications and have been shown to reduce bacterial counts and promote healing in infected wounds. Antibacterial properties of amniotic fluid are well documented and the presence of many potentially antibacterial factors has been demonstrated. No such factors have yet been found in amniotic membranes. We have applied a direct disc diffusion susceptibility test to try to establish the possible existence of such a factor. Amniotic membranes did not inhibit five bacterial species when tested at 3 X 10(6) and 3 X 10(8) colony forming units/ml. However, complete growth inhibition of all organisms was seen immediately under the amniotic membrane discs. These results support the hypothesis that the antimicrobial effect of amniotic membranes in vitro is due to their close adherence to the wound surface. PMID- 1754578 TI - Human placental lactogen (hPL) model for the normal pregnancy. AB - This study includes 75 females with normal pregnancies, and presents individual cases of longitudinal series of human placental lactogen (hPL). Samples for hPL levels are taken during the period from gestational week 26 and until labour. A modified Gompertz equation is defined, characterized as growth at a continuously decreasing exponential rate, which finally plateaus in gestational week 36. This modified Gompertz equation adequately fitted individual hPL series. The work describes that a final hPL forecast for the normal pregnancy could be obtained in gestational week 30 using knowledge on maternal height and age, combined with a single hPL sample. The present model was applied in six pathological pregnancies with intrauterine growth retardation, and in all cases measured hPL levels were below the model estimate. PMID- 1754579 TI - [Results of epidemiological and clinical studies of the prevalence of chronic nonspecific diseases of the respiratory organs among rural population]. AB - The results of many years' investigations conducted in 3 experimental republican regions are presented. The investigations were aimed at establishing the reliable indices of the prevalence of chronic nonspecific respiratory diseases in rural population and the development of preventive measures in subjects at a high risk of tuberculosis infection in certain patients with chronic nonspecific respiratory diseases who have some post-tuberculous lung changes. It is emphasized that rendering of the preventive and therapeutic aid to pneumologic patients requires joint efforts of phthisiatrists, pneumologists and therapeutists. PMID- 1754580 TI - [Smoking among medical students]. AB - A fundamental statistical analysis of the questionnaire given to 2089 first-year and last-year students of 9 medical institutes of the country was carried out within the framework of study of the "Smoking and Health" International Committee. The number of smokers per day was 21.6%. Awareness of smoking association with the development of certain diseases is 2-3 times higher in the last-year students than in the first-year ones. Among the nonsmokers 87.6% supported the need to limit smoking in public places, 79.2% to prohibit tobacco selling to children, 66.6% to prohibit advertisement of tobacco products and 82 supported the idea of instructing doctors in methods for treating smoking. Smokers were less enthusiastic in supporting the proposed measures. Among the smokers 53% claimed failure in giving up smoking. The main responsibility in banning smoking falls on medical profession. PMID- 1754581 TI - [Analysis of the knowledge of phthisiology among pediatricians]. AB - Analysis of an anonymous questionnaire given to 100 pediatricians at the postgraduate training department is given. Questions involved routes of infection, early detection, clinical aspects and prevention of tuberculosis in children and adolescents. The most typical aspects of inadequate knowledge of phthisiatrics by pediatricians were defined, which may negatively affect the antituberculosis aid given to children and adolescents. The findings were used for the adjustment of a program and the content of phthisiatrics training at the postgraduate training department. PMID- 1754582 TI - [What is respiratory insufficiency?]. PMID- 1754583 TI - [Diagnosis of pleurisy of tuberculous etiology]. AB - Among the 367 patients with the pleurisy syndrome examined in a specialized diagnostic department, 167 (45.5%) had tuberculous pleurisy and the active stage of pulmonary tuberculosis was diagnosed in 42 (25.1%); in 125 subjects pleurisy was an independent form of tuberculosis. The possibilities of the clinico roentgenologic, bioptic and bacteriologic diagnosis of the disease etiology have been studied in different variants of the X-ray picture (unblocked, partially sacculated, sacculated and adhesive pleurisy). PMID- 1754584 TI - [Status of the bronchi in patients with pulmonary tuberculosis and different haptoglobin phenotype]. AB - External respiration function test and bronchologic examination were conducted in 206 pulmonary tuberculosis patients with different haptoglobin (Hp) phenotypes. It was found that obstructive changes in peripheral portions of the bronchial tree were most common and marked among the revealed disorders of pulmonary ventilation function. These changes promote a decrease in the ventilation reserve to a great extent. As compared to Hp 2-1 carriers, specific endobronchitis and bronchial obstruction symptoms were significantly more frequent in patients with Hp 2-2. Bronchial obstruction symptoms alone were twice as frequent as in patients with Hp 1-1 than in Hp 2-1 carriers. The findings indicate that there is a close relationship between the status of the bronchi in pulmonary tuberculosis patients and the genetically determined Hp phenotype. PMID- 1754585 TI - [Clinical course, treatment and outcome of tuberculous meningitis in children]. AB - Data are given on the follow-up of 108 children between the ages of 6 months and 15 years who had tuberculous meningitis. A basilar form of meningitis was diagnosed in 70.4% of the children and meningo-encephalitic form in 29.6%. In most of the children meningitis developed in the presence of specific changes in the lungs; the course was typical in 74.1% and acute in 25.9%. Superinfection was seen in 64% of the children, late diagnosis and untimely hospitalization of children were noted in 31.5%. A clear relationship was revealed between disappearance of clinical signs and liquor cleansing and hospitalization terms. Treatment currently applied is effective. Cure was seen in 86.1% of the cases in the presence of significant residual changes (in meningoencephalitis) in 13.9%. The disease had a fatal outcome in 13.9% of the cases of late diagnosis. PMID- 1754586 TI - [Chemical elements in the blood, bronchial lavage fluid and lung tissue of patients with pulmonary tuberculosis and lung cancer]. AB - The examined groups included 58 patients with cancer, 61 subjects with pulmonary tuberculosis and 50 healthy persons as controls. The content of trace elements in blood, bronchial lavage fluid from the most affected portions of the lungs, and in pathologic and healthy lung tissues was determined by a C-115 atomic absorption spectrophotometer. The examination findings demonstrated that the content of blood serum ferric zinc and magnesium, and erythrocyte zinc, manganese, potassium and calcium was higher in patients with pulmonary tuberculosis than in those with lung cancer. At the same time the content of magnesium and calcium in bronchial lavage fluid was higher in persons with a malignant process than in those with pulmonary tuberculosis. As far as differential diagnosis of pulmonary tuberculosis and lung cancer is concerned, it is advisable to measure the levels of erythrocyte trace elements since the latter most precisely reflects their content in the lung pathologic tissue. PMID- 1754587 TI - [Diagnosis of mycotic infections in patients with tuberculosis of the respiratory organs]. AB - The basic clinico-diagnostic criteria are given which detect an intercurrent infection caused by opportunistic fungi of the Candida and Aspergillus genus. The antibacterial drugs of nonspecific action used in patients with destructive forms of respiratory tuberculosis promote the growth and reproduction of fungus flora and aggravate the course of the underlying process in the lung tissue. When there is intercurrent mycotic infection, the antifungal therapy produces a clinical effect in patients with combined pathology. PMID- 1754588 TI - [Results of clinical use of nicorette in the treatment of tobacco smokers]. AB - The results of nicorette therapy in 51 patients with tobacco dependence were analysed. Among the total number of patients 14 had ideational, 8 psychosomatic and 29 dissociated tobacco dependence. A year follow-up shows that 20 patients gave up smoking (predominantly with dissociated tobacco dependence). The clinical aspects of a reverse dynamics of the symptoms of a pathological tobacco addition, with consideration of the type of tobacco dependence and premorbid features of the course of mental cognition, show that nicorette possesses a certain clinical spectrum of action suppressing the activity of a secondary ideational component of pathological tobacco addiction. Nicorette may raise the level of a clinico differential therapeutic approach aimed at giving up smoking in the form of monotherapy or a combined therapy with the use of tranquillizers, neuroleptics and antidepressants. PMID- 1754589 TI - [Clinical course and outcome of pulmonary tuberculosis in rural population from the epizootically unfavorable regions]. PMID- 1754590 TI - [A method of studying mucociliary clearance in patients with inflammatory lung diseases]. PMID- 1754591 TI - [A modified method of determining the isoniazid levels in the blood serum and organs of animals]. PMID- 1754592 TI - [Value of different combinations of immunological signs for differential diagnosis of lung diseases]. AB - Stemming from the results of a complex immunologic examination of 653 patients with lung diseases, 4 immunologic reactions of highly diagnostic value were identified, i. e. specific antibody formation, blast transformation with PPD and PHA and spontaneous rosette formation. The most valuable combinations of these reactions were defined for each type of the pathology. For tuberculosis, 16 such combinations were found, including 5 without specific antibody formation; 5 in cancer; 3 in nonspecific inflammation; and 1 in sarcoidosis. Diagnostically important combinations of the above immunologic reactions are summarized in the Table whose use in differential diagnosis of doubtful cases of tuberculosis, cancer, nonspecific pneumonia and sarcoidosis can increase their diagnostic probability up to 0.95-0.99 in 30 per cent of the patients without employing invasive methods. PMID- 1754593 TI - [Anti-tuberculosis antibodies in the immunoenzyme test in relation to the effectiveness of chemotherapy of tuberculosis]. AB - A method of indirect solid-phase EIA was used to detect serum antibodies in 110 patients with destructive tuberculosis. The preparation with a molecular mass of 38-42 kD isolated from the mycobacteria H37Rv was used as an antigen. Changes in the level of antituberculous antibodies were found during treatment, which are most manifested in 4-6 months of antituberculous therapy and depend on treatment efficiency. The effective therapy is accompanied by a decrease in the level of antituberculous antibodies by that time, while in ineffective therapy it remains high. Hence, changes in the level of antituberculous antibodies may serve as an additional criterion of chemotherapy efficiency. PMID- 1754594 TI - [Prevention of side effects of specific chemotherapy in patients with pulmonary tuberculosis]. AB - Data are given related to a combined examination of 168 pulmonary tuberculosis patients in whom immunomodulating T-activin and levamisole chemotherapy was carried out in 40 subjects. In tuberculosis patients with significantly abnormal parameters of the immunity T-system, side effects of the antituberculosis drugs developed in 67.7%, while in those who were subjected to a general scheme of treatment with inclusion of the immunomodulating drugs in only 17.5%. T-activin was found to be highly effective in preventing side effects of the antituberculosis drugs. A diverse influence of the immunity modulating drugs on some T-lymphocyte classes was registered, which is essential in choosing the suitable modulator and regimen of its use. PMID- 1754595 TI - [Cytomorphological diagnosis of sarcoidosis in patients with lesions of the peripheral lymph nodes and respiratory organs]. AB - In sarcoidosis, the cytomorphologic pattern of aspirates shows a predominant progressive inflammation without exudative reaction and caseous necrosis, round granulomas with signs of polymorphism with the presence of mononuclear elements, giant cells by the "foreign body" type and development of pronounced fibrosis. PMID- 1754596 TI - [Ultraviolet irradiation of blood in patients with pulmonary tuberculosis]. AB - The described methods for ultraviolet blood radiation were used in 80 patients: 51 had tuberculosis of the bronchopulmonary system and 29 nonspecific pulmonary diseases. A marked clinical effect was confirmed by subjective and objective methods. In all cases blood pressure moderately decreased, there was a tendency to hypercoagulation decline, the erythrocyte count and hemoglobin level increased. The microstructure of blood elements studied by a scanning electron microscope showed formation of the rosette-forming structures in the blood and a significant increase in deformed erythrocytes. PMID- 1754597 TI - [Effect of carbon dioxide laser on Mycobacterium tuberculosis and microflora]. AB - The effect of CO2 laser on M. tuberculosis (MT) and nonspecific micro-organisms has been studied. Radiation of MT in suspension causes a decrease in the number of colonies. Laser action on MT and microflora after their growing in a solid nutrient media produces a bactericidal action in the exposed zone with the area of growth inhibition being in a direct proportion to the laser power and the time of its action. PMID- 1754598 TI - [Detection of destructive pulmonary tuberculosis in children at a hospital for somatic diseases]. AB - Tuberculosis-related examination of 123 children during hospital treatment in 2 pneumologic departments has revealed 9.8% of tuberculosis patients. Among the children with destructive lung processes one-third had tuberculosis in a destructive phase. Timely diagnosis of childhood tuberculosis in children's somatic hospitals, especially in those of a pneumologic type, requires the obligatory Mantoux test with 2 TU PPD-L and in children with destructive lung processes bacteriologic sputum examination for Mycobacterium tuberculosis. PMID- 1754599 TI - [Tuberculosis in the United States (review of foreign literature 1983-1989)]. PMID- 1754600 TI - [A rare case of intralobar sequestration associated with pulmonary tuberculosis]. PMID- 1754601 TI - [Incidence of cor pulmonale in chronic nonspecific lung diseases]. PMID- 1754602 TI - The regulation of adenylyl cyclase by receptor-operated G proteins. AB - The receptor regulated adenylyl cyclase system is a multiprotein complex which is a member of the family of the receptor-effector systems whose signal is transduced by heterotrimeric GTP-binding proteins. The system consists of stimulatory and inhibitory receptors (Rs and Ri), stimulatory and inhibitory G proteins (Gs and Gi) and the adenylyl cyclase enzyme (C). While quite specific in situ, receptors (stimulatory or inhibitory) from one source can activate the appropriate G protein from other cell types or species which in turn can act on C from other sources. Studies with chimeric proteins have shown that the various specificities (stimulatory or inhibitory) can be mapped to defined domains in both receptors and G proteins. The mechanism by which the heterotrimeric G proteins couple to the stimulatory and inhibitory signals is discussed in detail. Specifically, the data supporting collision coupling vs the shuttle mechanism is reviewed, as well as the role of beta gamma subunits in both the stimulatory and inhibitory signals. PMID- 1754603 TI - The potential importance of swainsonine in therapy for cancers and immunology. AB - Swainsonine, an indolizidine alkaloid, was initially used in biomedical research as a tool to investigate the biosynthesis and function of asparagine-linked 'complex' type oligosaccharide moieties of glycoproteins. Recently, swainsonine has generated interest in its potential use as an anticancer agent with reports that it (i) inhibits tumor growth and metastasis, (ii) augments natural killer (NK) and macrophage-mediated tumor cell killing, and (iii) stimulates bone marrow cell proliferation. The antineoplastic activity of swainsonine can be explained at least in part by augmentation of immune effector mechanisms. The potential application of swainsonine as an anticancer agent is discussed. PMID- 1754604 TI - Intracellular messengers and the control of protein synthesis. AB - The molecular events responsible for controlling cell growth and development, as well as their coordinate interaction is only beginning to be revealed. At the basis of these controlling events are hormones, growth factors and mitogens which, through transmembrane signalling trigger an array of cellular responses, initiated by receptor-associated tyrosine kinases, which in turn either directly or indirectly mediate their effects through serine/threonine protein kinases. Utilizing the obligatory response of activation of protein synthesis in cell growth and development, we describe efforts to work backwards along the regulatory pathway to the receptor, identifying those molecular components involved in modulating the rate of translation. We begin by describing the components and steps of protein synthesis and then discuss in detail the regulatory pathways involved in the mitogenic response of eukaryotic cells and during meiotic maturation of oocytes. Finally we discuss possible future work which will further our understanding of these systems. PMID- 1754605 TI - Morphologic and morphometric techniques for the detection of drug- and toxin induced changes in lung. AB - The lung is one of the main target organs of drug-induced toxicity. An assemblage of quantitative techniques is available to make precise determinations of structural effects. While stereology is the principal technique, particularly in its application to the parenchyma, other compartments such as the airways and vasculature demand modifications or different methods altogether. The new methods of molecular biology can now be used to uncover the mechanisms underlying drug toxicity and with a more rational use of image analysis are likely to yield quantitative data. Established techniques that quantify structural change combined with more novel approaches that utilize molecular interventions may emerge as exciting integrated approaches in this important field. PMID- 1754606 TI - Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1. AB - The harmful effects of Aflatoxin B1 (AFB1) are a consequence of it being metabolized to AFB1-8,9-epoxide, a compound that serves as an alkylating agent and mutagen. The toxicity of AFB1 towards different cells varies substantially; sensitivity can change significantly during development, can be modulated by treatment with xenobiotics and is decreased markedly in preneoplastic lesions as well as in tumors. Three types of resistance, namely intrinsic, inducible and acquired, can be identified. The potential resistance mechanisms include low capacity to form AFB1-8,9-epoxide, high detoxification activity, increase in AFB1 efflux from cells and high DNA repair capacity. Circumstantial evidence exists that amongst these mechanisms the glutathione S-transferases, through their ability to detoxify AFB1-8,9-epoxide, play a major role in determining the sensitivity of cells to AFB1. PMID- 1754607 TI - Piracetam in elderly motorists. AB - 101 elderly motorists with reduced reaction capacity were examined under real traffic conditions with regard to their driving ability. They were given a daily dose of 4.8 g piracetam or placebo over a six-week period in a randomised double blind study. The percentage of correctly solved sign-observance items, which reflects orientation and perception in real traffic conditions, increased in the placebo-treated test-group from 79.86% in the pretest to 80.07% in the retest, whereas the test subjects of the piracetam-treated group improved their performance from 77.08% to 84.16%. After being treated with piracetam for 6 weeks, the drivers showed a significantly better performance than the placebo group. Of particular interest is the finding that the test-subjects who had scored less than 80% in the pretest improved without exception in the retest after treatment with piracetam. PMID- 1754608 TI - Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study. AB - In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754609 TI - Extrapyramidal symptoms and their relationship to clinical efficacy under perphenazine treatment. A controlled prospective handwriting-test study in 22 acutely ill schizophrenic patients. AB - In order to verify the hypothesis of a strict relationship between clinical improvement and extrapyramidal side-effects, especially micrographia, twenty-two acutely ill schizophrenics were treated with perphenazine in a controlled prospective 28-day trial. During the study period, psychopathometric data, prolactin plasma levels, and handwriting samples were collected. According to the remission criteria fixed before the study began (both BPRS less than or equal to 25 and GAS greater than or equal to 80 points), 45.5% (10/22) of the total patient sample were classified as treatment responders. Handwriting tests were quantified in 21 patients. "Positive" handwriting results, i.e., a reduction of at least 13% in the overall area of 50% or more of the handwriting samples collected during the trial, were demonstrable in three of nine responders (33%) and nine of twelve nonresponders (75%). These results show that there is no positive correlation between clinical response and reduction in handwriting area. Consequently, the handwriting test is unable to predict clinical response. It is only one of a number of parameters with which to monitor the neurological side effects of neuroleptic treatment. Outcome parameters show that psychopathological remission can be achieved with low neuroleptic dosages and few or virtually no extrapyramidal side-effects. PMID- 1754610 TI - Misuse of zopiclone and convulsions during withdrawal. AB - It has been documented that benzodiazepines have the potential to cause dependence and withdrawal reactions, including convulsions. However, the available data concerning zopiclone, a nonbenzodiazepine hypnotic, are insufficient. The present study describes the case of a 36-year-old man who repeatedly misused zopiclone, in daily doses of 60-90 mg. Furthermore, the patient suffered from convulsion on two occasions following abrupt withdrawal of zopiclone. The concomitant use of alcohol, trimipramine, and promazine may have contributed to the development of convulsions. It is concluded that zopiclone may cause problems associated with misuse and withdrawal reactions similar to those of benzodiazepines. PMID- 1754611 TI - Side-effects of phototherapy in nonseasonal depressive disorder. AB - The data of the Berlin light therapy study were systematically reinvestigated for side-effects of light therapy as described in the literature. Forty-two patients with major depressive disorder (RDC), who also met the criteria of ICD-9 (296.1 and 296.3), were included. Patients were either given bright white-light treatment (2,500 lux) or dim red-light treatment (50 lux) from 7.20 a.m. to 9.20 a.m. every morning for a period of seven days. The study did not reveal any differences in side-effects between the two treatments. The results are discussed in relation to the two different treatment conditions. PMID- 1754612 TI - Trends in diagnostic ultrasound exposure. AB - Trends in exposure for diagnostic ultrasonic equipment and a contemporary survey of exposure values are presented. It is demonstrated that both time-averaged intensities and peak pressures have increased steadily over the last two decades. Currently available diagnostic equipment generates pulses for which the average worst-case rarefaction pressure, p-, is about 2 MPa in water, irrespective of the mode of operation. Overall the highest values of p- are found in short-focus beams. Average spatial-peak time-averaged intensities, I(SPTA), are greatest for pulsed Doppler operation at a little over 1 W cm-2. M-mode and colour Doppler operation have average values of I(SPTA) of about 100 mW cm-2 and imaging operates at about an order of magnitude lower again. Vaginal transducers differ little in operational exposure from other transducers. Exposure measurement on colour Doppler systems demands a knowledge of the effect of scanner controls on the field, and some details are given. PMID- 1754613 TI - Physics and Technology of Medical Ultrasound Conference. 15-16 April 1991, University of York, United Kingdom. PMID- 1754614 TI - Towards an ideal blood analogue for Doppler ultrasound phantoms. AB - If a phantom is to produce Doppler spectral waveforms accurately matching those that would be obtained in vivo, it is necessary to use a fluid that behaves like blood in vivo, both acoustically and rheologically. The use of blood itself is undesirable and an analogue is required. Blood exhibits non-Newtonian behaviour as a result of aggregation of erythrocytes at low shear rates. This behaviour affects flow not only in sub-millimetre diameter vessels, but also in large scale structures. An alternative to blood is described that uses finely powdered nylon suspended in a mixture of glycerol and water. The nylon particles used have dimensions and density close to those of erythrocytes and they aggregate at low shear rates to give non-Newtonian behaviour. Viscosity may be varied over a wide range by the addition of liquid detergent. Consideration is given to the importance of haematocrit in modelling pulsatile and disturbed flows as it affects the haemodynamics of flow and the backscattered power of an ultrasound beam. This adaptable blood analogue is suitable for use in models of both large structures and fine vessels. PMID- 1754615 TI - Electromagnetic radiofrequency interference with Doppler equipment. AB - Doppler ultrasound equipments incorporate radiofrequency (RF) receivers operating at the microvolt level and are liable to interference from radiated fields and mains disturbances. The most significant interference routes are: radiation from radio broadcast, paging, communication and diathermy picked up on the transducer and patient acting as an aerial; and mains disturbances from diathermy, x-ray sets, motors and thyristor controls, etc, reaching the equipment interior. Direct mains interference can be reduced by proper design incorporating a mains filter, a low RF leakage enclosure, a ground plane, careful layout and further screening of the receiver circuits. Pick-up via the transducer occurs even if the signal leads are completely screened because an RF potential can exist between transducer and equipment enclosure due to the considerable impedance at RF of any wire or cable, typically 70 omega at 5 MHz for 2 m. This potential, reduced by about 50-60 dB, appears at the receiver input because of imperfect common mode rejection of the coupling cable. As a result, induced voltages above 100-300 microV may cause problems. It is shown that such levels can easily result from the interfering field strengths of 1 mV m-1 or more that may be experienced in a hospital environment. On the other hand, field strengths of 300 microV m-1, as generally allowed by regulatory standards at 3 m from interfering sources, should not cause much effect. Other interference can arise from modulation of a strong RF signal by mains frequency power components in the Doppler equipment and from associated computer circuits. These require careful layout to reduce electric and magnetic coupling, decoupling and filtering of power supplies and components, screening of RF circuits and particular attention to the reduction of power and computer signal currents flowing in RF signal earth paths. Finally, some initial simple acceptance tests for interference susceptibility are proposed, based on the application of 300 microV of RF signal between transducer body and equipment enclosure and 10 mV to the mains supply. PMID- 1754616 TI - Prediction of non-linear propagation in water due to diagnostic medical ultrasound equipment. AB - There is a well established requirement for making output measurements on medical ultrasound equipment, in particular for safety and calibration purposes. In addition there is a need for non-linear propagation models to allow predictions to be made for in vivo pressure fields of systems ranging from lithotripters to diagnostic imaging sets. In the past it has been shown that good agreement can be found between experiment and theory for transducers that behave as perfect pistons but little work has been published on comparisons for 'real' medical ultrasound systems. This paper compares experiment with theory for a medical ultrasound system operating in water. Pressure field measurements are presented for a Philips 3.5 MHz, 13 mm diameter, 'long internal focus' (LIF) transducer. The measurements were made using a membrane hydrophone in water. Initially the transducer was driven continuously with a function generator at low amplitude so that the effective aperture radius and focal length could be determined. The transducer was then driven by a Philips 'sono-Diagnost B' imaging system which produced a short finite amplitude pulse. The results are compared with a finite difference model based on the parabolic approximation to the non-linear wave equation. Reasonable agreement (typically 10-15%) is shown for spectral magnitudes although some difficulty was encountered in accurately characterizing the transducer in terms of its geometry and drive waveform. PMID- 1754617 TI - Forces acting in the direction of propagation in pulsed ultrasound fields. AB - This paper considers some non-thermal effects resulting from absorption of acoustic energy from an ultrasound beam. An experimental investigation of the location of the 'source pump', responsible for the generation of streaming in high amplitude diagnostic fields in water, is reported. Acoustically transparent membranes were inserted in the ultrasound field in order to restrict the streaming volume. It is shown that the major contribution to an acoustic stream is generated in the region near to the focus of a transducer where the intensity in the beam and the degree of non-linear distortion are both high. In the second part of the paper a simple model of non-linear propagation is used to predict the magnitude of the maximum pressure gradient induced in a medium by the absorption of acoustic energy from a beam. Propagation in water, in tissue and in amniotic fluid are considered. Within the limitations of this model it is shown that the pressure gradients induced in pulsed acoustic fields do not result in the ultimate shear stress of tissue being exceeded. PMID- 1754618 TI - The physics of liquid impact, shock wave interactions with cavities, and the implications to shock wave lithotripsy. AB - This paper reviews research on the physics of liquid impact and the behaviour of cavities when a shock passes over them. It is shown that the problems are related since when a cavity collapses near a solid surface, or is collapsed by a shock wave, the collapse is asymmetric and a liquid jet is produced which can impact an adjacent solid. The implications of this research to shock wave lithotripsy are emphasized. Finally, the paper describes the development of a device, based on liquid jet impact, for fragmenting kidney stones. PMID- 1754619 TI - Measurement of lithotripsy pulses through biological media. AB - Lithotripsy is now the method of choice for the treatment of renal calculi. The mechanism of destruction is not clearly understood, and detailed knowledge of the shock-wave characteristics at the calculus would aid understanding of the phenomenon. Current methods of measuring the pressure pulse by observing it through a water path are not well characterized, and the results may not represent the actual pressure fluctuations produced in vivo. In order to determine the actual pressure pulse experienced at the site of the calculus, measurements have been made through a variety of biological media. The results show that there are considerable differences between measurements taken through a water path and through biological media. This paper describes the pressure fluctuations in the time domain. The implications of the results for lithotripsy are discussed. PMID- 1754620 TI - High intensity focused ultrasound for the treatment of rat tumours. AB - Discrete implanted liver tumours in the rat have been exposed to arrays of 1.7 MHz ultrasound lesions. Focal peak intensities in the range 1.4-3.5 k Wcm-2 were used for an exposure time of 10 s. It has been demonstrated that where the whole tumour volume was exposed to the focused ultrasound beam, no evidence of tumour growth could be detected histologically. Where the ultrasonic lesion array was not contiguous, regrowth occurred. Preliminary histological studies confirmed this finding. PMID- 1754621 TI - Resolution and information limitations from transducer arrays. AB - The factors limiting the resolution achievable with array-based imaging methods are considered. The limitations on beamwidth and field of view for beam scanning systems are first examined using plane wave diffraction theory, treating focusing and any array curvature as separable to the plane wave analysis. It is found that in all cases the number of half-beamwidths (maximum to null) across the field of view cannot exceed the number of electrically addressable elements in the array. The minimum beamwidth achievable by strong focusing is shown to be limited to twice the inter-element pitch. Digital reconstruction is then considered as an alternative to beam scanning. Here the number of image points recoverable across the field of view is equal to the number of elements in the array. The mathematical equivalence of the two methods is demonstrated, and the inference is made that the half-beamwidth represents a fundamental measure of lateral resolution. Alternative array configurations, suitable for CT methods, are then compared to probe arrays and it is found that the total number of resolution cells within a two-dimensional image is dependent on the pulse length and number of elements, rather than on the array configuration and imaging method. This again reveals the fundamental similarity of the various methods, essentially in combining position line information from the separate elements, albeit in different orders. Finally an expression for the information capacity of a scanning system is presented which relates the limitations on spatial and contrast resolution to the bandwidth and dynamic range of the system and the number of elements in the array. PMID- 1754622 TI - Experimental studies in transmission ultrasound computed tomography. AB - The reconstruction of the speed-of-sound distribution within a target can be achieved by CT techniques from measurements on transmitted ultrasonic pulses. The mathematical relationship between speed-of-sound imaging and the conventional CT situation is explained. An experimental system, which has been developed to investigate speed-of-imaging and other forms of in-vivo ultrasound CT, is described, along with the techniques used for data acquisition and image reconstruction. These include measurement of pulse time-of-flight by the threshold or cross-correlation methods. Techniques for reducing artifacts in speed-of-sound images are also described, such as median filtering and modified Shepp-Logan filtering. These techniques have been used to obtain high quality speed-of-sound images of various phantoms. Images of tissue in-vitro have been less satisfactory, because of refraction and attenuation effects. Ways of overcoming these difficulties in an improved system are proposed. PMID- 1754623 TI - Dependence of the velocity and attenuation of ultrasound in bone on the mineral content. AB - Measurements of the attenuation and velocity of ultrasound from 0.3 to 0.8 MHz have been performed on a number of bovine cancellous bone samples. The influence of bone mineral content has been isolated by measuring the acoustic properties of the samples at various stages of demineralization resulting from controlled nitric acid attack. The correlation coefficient r, between the attenuation at different frequencies and bone density was found to be in the range 0.68-0.97. Broadband ultrasonic attenuation (BUA) was also calculated and produced r values between 0.84 and 0.99. The velocity measurements indicated a correlation greater than 0.97 in all cases. Thus velocity is the parameter most sensitive to changes in bone mineral density alone. Attenuation and BUA are less well correlated presumably because of a sensitivity to minor structural change. PMID- 1754624 TI - Assessment of hybrid speckle reduction algorithms. AB - A consequence of employing coherent detection methods in medical ultrasound imaging systems is the occurrence of interference effects in the received echo field, which produce the speckle artefact. Speckle can severely degrade the information content of the image, and its efficient removal from ultrasound pulse echo images is the focus of a number of research projects. Traditionally, the approach towards speckle reduction in pulse-echo images has been based on two classes of technique, either employing some form of spatial/frequency compounding or a data (image) filter. Both approaches have inherent shortcomings, and two alternative techniques are suggested here: 'local frequency diversity' and 'frequency differencing'. These algorithms deterministically identify where speckle occurs, and correct for speckle only within short, localized, corrupted segments of the A-line. This provides the potential for real-time implementation. Simulated and clinical in vivo images have been obtained, and the capabilities of the alternative speckle reduction algorithms are assessed against the more conventional approaches. PMID- 1754625 TI - Platelet serotonin in subtypes of schizophrenia and unipolar depression. AB - In subtypes of schizophrenia and unipolar depression, both increased and decreased levels of platelet serotonin were found. Hyperserotonemia was usually observed in patients with psychotic features (i.e., in paranoid schizophrenia and psychotic depression). Hyposerotonemia, although less common than hyperserotonemia, was present in nonparanoid schizophrenia and nonpsychotic depression (i.e., in patients without psychotic symptoms). A sex difference in platelet monoamine oxidase activity was observed among healthy subjects, but not among schizophrenic patients. The activity of platelet monoamine oxidase in paranoid and nonparanoid schizophrenic patients did not differ from that in healthy subjects. The findings in this study suggest that biological differences between subtypes of unipolar depression or schizophrenia might depend upon the presence of psychotic symptoms. PMID- 1754626 TI - Genetic factors for the span of apprehension test: a study of normal twins. AB - The Partial Report Span of Apprehension test has been found to detect cognitive deficits in some first degree relatives of schizophrenic patients. To assess the relative contribution of genetic vs. environmental factors on this measure, 19 monozygotic and 14 dizygotic female twin pairs, selected from a normal population, were tested on the Span of Apprehension test and an IQ test. Both Span of Apprehension test performance and IQ score had high heritabilities: 0.65 and 0.71, respectively. The mode of transmission for performance on the Span of Apprehension test appears to operate in a nonadditive manner. A multivariate behavioral-genetic model applied to the Span of Apprehension and IQ measures indicated that slightly less than half of the genetic effects important for the Span of Apprehension test are found in common with the genetic factors important for IQ. The phenotypic correlation between the Span of Apprehension and IQ measures can be attributed entirely to genetic factors. The influence of unique genetic components in the performance of the Span of Apprehension test in the general population heightens the promise of this measure as a genetic marker for schizophrenia. PMID- 1754627 TI - An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia. AB - Schizophrenic women have been consistently found to have a later age of onset and a less severe clinical course of illness as compared with schizophrenic men. Because these differences are not explained by diagnostic artifacts or sociocultural factors, we tested the hypothesis that they are determined by the influence of the gonadal hormones testosterone and estradiol on dopaminergic (DA) neurotransmission. We used animal models in which the effects of the hormones on behavioral changes induced by the DA antagonist haloperidol (catalepsy) and by the DA agonist apomorphine (oral stereotypies, grooming and sitting behavior) were investigated in neonatal and in adult treated rats. No consistent effects of testosterone were observed. Estradiol significantly reduced the behavioral changes induced by both haloperidol and apomorphine, and this effect was more pronounced in neonatally treated animals. These results suggest a downward regulation of DA neurotransmission by estradiol, which is supported by the results of 3H-sulpiride binding determinations in brain homogenates from the same animals: estradiol caused a 2.8-fold reduction of DA receptor affinity to sulpiride. Our findings suggest that estradiol might act as a protective modulator in schizophrenia by enhancing the vulnerability threshold for psychosis through the downward regulation of DA neurotransmission. Such mechanism could explain, at least in part, the later onset and the more favorable course of schizophrenia in female patients. PMID- 1754628 TI - A longitudinal study of cerebrospinal fluid acetylcholinesterase in delirium: changes at the acute stage and at one-year followup. AB - Cerebrospinal fluid acetylcholinesterase (CSF AChE) was determined for elderly delirious patients during the acute stage and after a 1-year followup, and the AChE levels were compared with those of age-equivalent controls. At the acute phase, the AChE levels of the delirious patients were in the same range as those of the control group, but during the followup, a slight declining trend was observed. These results do not unambiguously support the previously suggested role of cholinergic dysfunction in the pathogenesis of acute delirium, although the augmented striatal release of AChE in hyperkinetic and mixed delirium may mask the involvement of cholinergic neurons. PMID- 1754629 TI - Reliability and validity of the Apathy Evaluation Scale. AB - This article presents evidence for the reliability and construct validity of the Apathy Evaluation Scale (AES). Conceptually, apathy is defined as lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Operationally, the AES treats apathy as a psychological dimension defined by simultaneous deficits in the overt behavioral, cognitive, and emotional concomitants of goal-directed behavior. Three versions of the AES (clinician, informant, and self-rated) were evaluated for 123 subjects, ages 53-85, meeting research criteria for right or left hemisphere stroke, probable Alzheimer's disease, major depression, or well elderly control. Multiple forms of reliability (internal consistency, test-retest, and interrater) were satisfactory. Several types of validity evidence are presented for each version of the scale, including the following: ability of the AES to discriminate between groups according to mean levels of apathy, discriminability of apathy ratings from standard measures of depression and anxiety, convergent validity between the three versions of the scale, and predictive validity measures derived from observing subjects' play with novelty toys and videogames. Guidelines for the administration of the AES are presented, along with suggestions for potential applications of the scale to clinical and research questions. PMID- 1754630 TI - Smooth pursuit and saccadic eye movements and neurological soft signs in obsessive-compulsive disorder. AB - Patients with obsessive-compulsive disorder (OCD) demonstrate an increased number of neurological soft signs as well as neuroanatomic abnormalities detected with modern imaging techniques. Quantitative analysis of eye movements has proved fruitful in investigations of other neuropsychiatric disorders with similar findings. Therefore, we studied the smooth pursuit and saccadic eye movements of 8 OCD patients and 12 normal controls using infrared oculography and computerized pattern recognition software. We also measured neurologic soft signs using a standardized rating instrument. Despite having an increased number of neurological soft signs, OCD patients' performance on a variety of measures of eye movement was not significantly impaired. Neither the severity of obsessions or compulsions nor the number of neurologic soft signs correlated with any of the parameters of eye movement function. We conclude that OCD patients do not have prominent oculomotor dysfunction and that eye movement dysfunction and neurologic soft signs are not inextricably linked. PMID- 1754631 TI - Is there a relationship between MHPG and anxiety in depressed patients? AB - Previous studies of the relationship between anxiety and 3-methoxy-4 hydroxyphenylglycol (MHPG) in depression have produced conflicting results. The possibility that different definitions of anxiety may have created these discrepant findings was explored. There was no convincing evidence that MHPG was associated with any of a wide range of different anxiety measurements that encompassed the anxiety concepts of somatic anxiety, psychic anxiety, agitation, or situational stress. The relationships of anxiety ratings to each other were also examined. PMID- 1754632 TI - Weight change in depression: influence of "disinhibition" is mediated by body mass and other variables. AB - The direction of weight change (gain or loss) in depression has recently been found to be a stable characteristic of patients across depressive episodes. A search for determinants of the direction of weight change revealed two candidates: the body mass index (BMI) (weight in kilograms/height in meters squared) and a psychological variable, "disinhibition" of dietary restraint. The present study, of 68 patients with a history of recurrent depression, found a significant correlation between BMI and weight change; in other words, heavier persons were more likely to gain weight if depressed. There was also a correlation between "disinhibition" and weight change. "Disinhibition" correlated with BMI and, when controlled for BMI, age and sex, the correlation between "disinhibition" and weight change fell to insignificance. We conclude that BMI along with age and sex mediated the correlation between "disinhibition" and weight change. PMID- 1754633 TI - Electroencephalographic sleep measures in prepubertal depression. AB - Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects. PMID- 1754634 TI - Dose-dependent reduced haloperidol/haloperidol ratios in schizophrenic patients. AB - Plasma haloperidol (HAL) and reduced HAL (RHAL) concentrations were measured in 113 Chinese schizophrenic patients. Daily doses of HAL ranged from 8 to 65 mg. Samples were obtained under steady-state conditions and drawn 10-12 hours after the bedtime dose and before the morning dose. In all, 313 blood samples were collected. Multiple samples were obtained at the same doses in 63 patients and at two or three different doses in 31 patients. HAL and RHAL concentrations were assayed by high performance liquid chromatography. Interpatient variation in plasma HAL levels at a given dosage was up to sixfold. However, there was a high positive correlation between plasma levels and daily dosages with the equation of HAL plasma level (ng/ml) = 0.88 x dosage (mg/day) -0.56 or 46.0 x dosage (mg/day/kg) + 0.28. The expected values are about 15-55% higher than those obtained from non-Chinese patients as reported in the literature. The RHAL/HAL ratios were dose-dependent. The greater the dose used, the higher the ratio. An upper therapeutic limit of plasma HAL level is suggested to be 25 ng/ml, which can be achieved at dosages about 30 mg/day in most Chinese patients. Based upon the dose-dependent increase in RHAL/HAL ratios, the importance of RHAL in determining the therapeutic benefit of HAL treatment is discussed. PMID- 1754635 TI - Effects of ritanserin on the behavioral, neuroendocrine, and cardiovascular responses to meta-chlorophenylpiperazine in healthy human subjects. AB - Ten healthy male subjects were administered i.v. meta-chlorophenylpiperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans. PMID- 1754636 TI - Effects of auditory stimulation during rapid eye movement sleep in healthy volunteers and depressed patients. AB - Auditory and somesthesic forms of stimulation have substantially increased rapid eye movement (REM) sleep in cats. We investigated whether auditory stimulation, applied during REM sleep or outside REM sleep, would have similar effects in normal volunteers. We also administered auditory stimulation to depressed patients during REM sleep. Subjects were studied during 1 acclimatization night, 2 baseline nights, 4 consecutive nights with auditory stimulation, and 1 followup night without auditory stimulation. Normal volunteers were randomly divided into Group R, which received auditory stimulation during each REM sleep episode, and Group NR, which received auditory stimulation at the end of each REM sleep episode. Depressed patients (Group D) received auditory stimulation during each REM sleep period. Only Group R showed increased REM sleep time during the nights of auditory stimulation and throughout the followup night. This group also increased their sleep efficiency. Group NR showed reduced sleep efficiency due to an increase in both the duration and frequency of awakenings. Group D did not show increased REM sleep time, but did show shortened REM sleep episodes, increased REM sleep frequency, and increased duration of awakenings. Group D did not show clinical changes. PMID- 1754637 TI - The cholinergic REM induction test with RS 86 after scopolamine pretreatment in healthy subjects. AB - A shortened latency of rapid eye movement (REM) sleep is one of the most stable biological abnormalities described in depressive patients. According to the reciprocal interaction model of non-REM and REM sleep regulation, REM sleep disinhibition at the beginning of the night in depression is a consequence of heightened central nervous system cholinergic transmitter activity in relation to aminergic transmitter activity. A recent study has indicated that muscarinic supersensitivity, rather than quantitatively enhanced cholinergic activity, may be the primary cause of REM sleep abnormalities in depression. The present study tested this hypothesis by treating healthy volunteers for 3 days with a cholinergic antagonist (scopolamine) in the morning, in an effort to induce muscarinic receptor supersensitivity. On the last day of scopolamine administration, RS 86, an orally active cholinergic agonist, was administered before bedtime to test whether this procedure would induce sleep onset REM periods. Whereas scopolamine treatment tended to advance REM sleep and to heighten REM density in healthy controls in comparison to NaCl administration, the additional cholinergic stimulation did not provoke further REM sleep disinhibition. This result underlines the need to take a hypofunction of aminergic transmitter systems into account in attempts to explain the pronounced advance of REM sleep typically seen in depressives. PMID- 1754638 TI - Effects of green or white light for treatment of seasonal depression. AB - Twelve subjects with winter depression were treated with equal quanta of green or white light in a randomized crossover study. Each treatment condition consisted of 2 hours of exposure each morning for 1 week, with at least 1 interventing week without treatment. Ratings made without knowledge of treatment condition were done before and after each condition. Both treatments significantly reduced depression ratings. White light was significantly more effective than green light in reducing endogenous symptoms, but not the "atypical" symptoms that are common features of winter depression. Furthermore, sequence of treatment conditions influenced antidepressant responses. Broad-band white light may be optimal for maximizing therapeutic response. PMID- 1754639 TI - Seasonal variations in mood and behavior in the general population: a factor analytic approach. AB - In a mailed survey conducted at four centers--Nashua, NH; New York, NY; Washington, DC; and Sarasota, FL--1,671 respondents provided information on monthly variations in 10 behavioral categories representing extremes in the areas of mood, socializing, appetite, weight gain/loss, and sleep length. A 10-factor solution revealed the following factors: (1) a winter weight gain factor; (2) a winter depression factor; (3) a winter hypersomnia factor; (4) a summer weight gain factor; (5) a summer hypersomnia factor; (6) a summer depression factor; (7) a winter socializing factor; (8) a winter weight loss factor; (9) a fall depression factor; and (10) a possibly mixed factor. Factors consistent with winter seasonal affective disorder were positively correlated with latitude, while those consistent with summer seasonal affective disorder were negatively correlated with latitude. PMID- 1754640 TI - Elevated serum lactate associated with panic attacks induced by hyperventilation. AB - Several lines of evidence suggest that lactate metabolism may be altered in panic disorder. We recently reported exaggerated increases in serum lactate in panic patients following hyperventilation during glucose infusion. In the current study, lactate metabolism was stimulated by hyperventilation following glucose ingestion in 12 panic patients and 12 controls. The seven patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients or controls. The lactate response was significantly correlated with peak ratings of anxiety and panic symptoms, but not correlated with insulin or cortisol levels, heart rate, pCO2, adiposity, exercise habits, or diet. Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate. PMID- 1754641 TI - Cortisol levels in generalized anxiety disorder. PMID- 1754642 TI - Music psychopathology. IV. The course of musical expression during music therapy with psychiatric inpatients. AB - The music therapeutic productions of 67 psychiatric inpatients were analyzed concerning a systematic variation in the course of therapy. The impairment of performance was not as regular as with customary music, nevertheless with growing remission it was reversible in all diagnostic subgroups. The change for the better of rhythmic and motor skills of endogenous-depressed patients was seen to the same extent as with traditional music. The polarity profile developed for the assessment of music proved meaningful in the characterization of music therapeutic utterances. PMID- 1754643 TI - Long-term prognosis of schizophrenia. AB - The question of determining prognostically relevant features for schizophrenia was approached with multivariate statistical methods applied to the data from the Bonn longitudinal study of 502 schizophrenic patients. In this study, personal interviews according to a clinical classification scheme allowed every patient to be ranked within each of three different outcome classes: psychopathological remission, occupational remission, and course type. Our multivariate analysis encompassed a total of 50 items pertinent to the time up to and including the first 6 months after the first psychotic manifestation. Despite the introduction of mathematical methods considerably more sophisticated than those employed in earlier studies, no satisfactory solution could be found to the problem of predicting end states of schizophrenia. Reliable predictions could be made only for 'extreme' end states (i.e. full remission versus (1) characteristic residues in the narrower sense; (2) total unemployment, or (3) surging or simple courses to mixed residues or to typical schizophrenic defect psychoses). Accordingly, sufficiently reliable assertions applied only to a minority of about 1/3 of patients, whereas for the majority of 2/3, no generalizable prognostication was possible (67-71% true-positive predictions on 36-63% of total population in extreme states). By contrast, our analyses have clearly uncovered a fundamental problem of investigations into the long-term prognosis of schizophrenia: the extreme dependence of results on the clinical definition of end states. The further the phenomenon 'end state' is qualitatively subdivided, the poorer and less reproducible is the mutual discrimination between intermediate states and the less reliable are allocations of patients to these intermediate states by means of multivariate classifiers. Furthermore, our analyses have also demonstrated the usefulness of multivariate, adaptive procedures for investigations into the structural properties of long-term courses, so that predictions might be considerably improved if more reliable definitions of schizophrenic end states are available. PMID- 1754644 TI - Attention, meaning, and somatization: a psychophysiological view. AB - This paper provides a discussion of a psychophysiological approach to somatization based on the notions of attention and meaning. It is suggested that several clinical features may be described, explained, and modified with the aid of these concepts. PMID- 1754645 TI - Schneiderian versus Bleulerian schizophrenia and basic symptoms. AB - Using the 'polydiagnostic approach' method, the relationship between basic symptoms (BS) and Bleulerian and Schneiderian types of schizophrenia is studied. Eighty-six schizophrenic patients (RDC criteria) were studied using the Frankfurt Complaint Questionnaire for the evaluation of the BS. The patients were classified according to the type of symptoms predominant in Schneiderian (n = 32), Bleulerian (n = 12) and mixed (n = 42) schizophrenics. The patients with Schneiderian and mixed schizophrenia displayed more BS than those having Bleulerian schizophrenia. Significant differences (p less than or equal to 0.05) were found on the subscales of Perception (simple), Language, Memory, Motoric and Loss of automatism, in factors 1, 2 and 4, and in the total score. The results suggest that, from the perspective of the BS, Schneiderian schizophrenia is different from Bleulerian and that the BS may have the same production mechanisms as Schneider's FRS, the difference between them being in the different degree of phenomenological expression. PMID- 1754646 TI - The syndrome of intermetamorphosis. AB - A series of 154 patients suffering from the syndrome of intermetamorphosis or its variants is discussed in terms of this misidentification syndrome's historical, classification, diagnostic, and psychosocial aspects. One case is presented in detail. PMID- 1754647 TI - A study of thought disorder in paranoid and non-paranoid schizophrenia. AB - Thought disorder was studied in 21 paranoid and 24 non-paranoid schizophrenics fulfilling the research diagnostic criteria using the Thought, Language and Communication Scale. Chronic paranoid schizophrenics more often had tangentiality. Other thought disorders were similar in paranoid and non-paranoid schizophrenics. PMID- 1754648 TI - Psychiatric aspects of male genital self-mutilation. AB - From the beginning of the century to this day 57 cases of male genital self mutilation have been reported in the English literature. In German publications we found 5 case descriptions. Although no precise data are available on the prevalence of male genital self-mutilation, such acts are presumably much more frequent than the small number of published cases would suggest. In the literature several features are regarded as risk factors for self-mutilation, such as e.g. homosexual or transsexual tendencies, repudiation of the male genitals, absence of a competent male for identification during childhood, feeling of guilt for sexual offences, and self-injury in the anamnesis. The most frequent diagnoses are schizophrenia and affective psychosis; alcohol intoxication was diagnosed in about one-fourth of the cases published. In the present paper we summarize data from the literature on epidemiology, psychopathology, psychodynamic and sociocultural factors in male genital automutilation and we describe 2 new cases of self-castration in which several of the risk factors described above were observed. We conclude that although it is difficult to estimate the risk of self-castration in view of the heterogeneity of the respective patient groups, the danger of such deeds should be kept in mind if the above factors are present. PMID- 1754649 TI - Delusional hypochondriasis: nosographic evaluation, clinical course and therapeutic outcome of 5 cases. AB - Five cases of delusional hypochondriasis are reported. Their nosographic position is discussed in the light of recent literature, DSM-IIIR, Present State Examination and ICD-9 classification criteria of hypochondriacal symptomatology. PMID- 1754650 TI - Scale for Assessment of Thought, Language and Communication in psychotic in patients. AB - The reliability and usefulness of the Scale for Assessment of Thought, Language and Communication was evaluated in a group of psychotic in-patients. A very high interrater reliability (0.75-1.0) and an optimum rate-rerate reliability (0.50 1.0) were found on the individual items of the scale as well as the global rating. Since the scale has a good scope in different clinical and research settings, it was necessary to evaluate its reliability at a place other than where it originated. This study confirms its usefulness in the field of both clinical practice and research. PMID- 1754651 TI - Changes in the electrodermal activity of schizophrenic patients associated with changes in the expressed emotion status of their relatives. AB - Thirty-nine relatives of schizophrenic patients, who had been rated as high on Expressed Emotion (EE) during the patients' admission for an acute episode, were re-rated on EE 9 months after discharge from the index admission. Electrodermal activity was recorded from the patient during a 15-min period when the relative was absent and a similar period while the relative was present. Recording took place during the index admission and at a 9-month follow-up. A comparison was made between those patients whose relatives remained high EE at follow-up (Stables) and those whose relatives change to low EE (Decreasers). No differences were apparent between these two groups, however, differences were found within groups. At admission both groups showed an increase in electrodermal measures from the relative-absent period to the relative-present period. At 9-month follow up, the Stables still exhibited this direction of change, whereas the Decreasers showed a decrease in electrodermal activity between these periods. PMID- 1754652 TI - Delusional psychoses associated with unpatriotic conduct during World War II: a long-term follow-up study. AB - Of a large sample of patients with paranoid psychoses consecutively admitted to the Psychiatric Department, University of Oslo, during a period after World War II, 10 patients (6.3%, 9 women and 1 man) became ill through accusations of unpatriotic conduct during the war. The psychosis seemed precipitated in connection with legal procedures against the patient in 3 cases, and against close relatives in 2 patients. In 2 cases mixed precipitating events were present, while the psychosis in 3 cases had a connection with the woman being intimate with occupation soldiers. Discharge diagnosis according to DSM-III was schizophrenia (n = 2), schizophreniform disorder (n = 4), schizoaffective disorder (n = 1), major depressive disorder (n = 1), mania (n = 1), and atypical psychosis (n = 1). The patients have been followed up twice, with a mean 31 years of observation. Course and outcome varied, mostly according to the diagnosis. Most patients had a favorable global outcome, although they had a tendency to keep up their social isolation. None of the patients felt they had done anything wrong or regretted their behavior during the war. PMID- 1754653 TI - 12-year clinical course of schizophrenia in hospital and night clinic patients over the period from 1971/1973 to 1983. Longitudinal study from 1971/1973 to 1983. AB - A sample of 46 schizophrenic patients (26 men and 20 women) from a night clinic (N subjects) with an average age of 21.7 years at the time of first manifestation of the illness and a sample of hospital inpatients (H subjects) matched for diagnosis, sex, and age were followed up from 1971/1973 to 1983. The average age of the patients in 1983 was 40 years. The course of the illness and the pattern of hospitalization were investigated by personally questioning each patient and by scrutinizing all the case history records and other relevant documents; for each clinical cycle of illness, consisting of an overt phase followed by a quiescent interval, a case control sheet was filled out. The duration of illness was 18 years for the N subjects and 15 years for the H subjects. Longitudinal analysis of these years of illness in both patient samples showed a marked decrease in the number and duration of overt phases and stays in hospital, but a progressive aggravation of residual symptomatology during quiescent intervals and a progressively decreasing ability to work and earn a living.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754654 TI - Discriminating schizophrenics from borderline patients: study with the Holtzman Inkblot technique. AB - The present study tried to discriminate acute (n = 25) and chronic schizophrenics (n = 25) from borderline patients (BLP; n = 30) on the basis of deviant verbalizations as assessed by the Holtzman Inkblot Technique (HIT). A 30-card version of the HIT was used. It was possible to separate BLPs and schizophrenics with quite good results: 77% of the BLPs, 80% of the acute schizophrenics and 92% of the chronic schizophrenics could be classified correctly based on the less severe deviant verbalizations (DVs) which were more frequent in the BLPs and based on the most severe forms of DVs, i.e. Incoherence, neologism and Perseveration (which were more frequent in the schizophrenic patients). Furthermore, it could be demonstrated that BLPs can be separated from neurotics using the 30-card version of the HIT, the resulting scores being nearly as high as those on the basis of the 45-card version. In another comparison, neurotics (n = 30) were discriminated from normals (n = 35) using the less severe DVs, which were more frequent in the neurotics: here, 74% of the normals and 73% of the neurotics could be classified correctly. PMID- 1754655 TI - Fatherhood, impending or newly established, precipitating delusional disorders. Long-term course and outcome. AB - Psychopathological reactions to fatherhood are probably not so infrequent as they would seem from psychiatric literature. In a material of paranoid psychoses, impending or newly established fatherhood was considered the main precipitating factor in 4 patients (i.e. 2.4%), compared with 7% of the female psychoses precipitated by pregnancy, childbirth or nursing. Two of the men were bachelors, insecure and inhibited, feeling compromised or helpless in the new situation. Two men were married, passive, avoidant in their personality, strongly dependent on their wives. The course and outcome varied according to the diagnoses; 2 cases having a favorable and 2 an unfavorable course and outcome. Physicians, including psychiatrists, should bear in mind that fatherhood is a possible precipitating factor for paranoid psychoses in male patients. PMID- 1754656 TI - Diurnal variations of mood and sleep disturbances during phototherapy in major depressive disorder. AB - The influence of diurnal variations of mood (DVM) and sleep disturbances on treatment response was investigated in 42 patients with major depressive disorder (not SAD) under the treatment of either bright white light (2,500 lx) or dim red light (50 lx). We found only a slight influence in certain subscales of DVM and no influence of sleep disturbances. These results are discussed under a clinical point of view and with respect to phase shift theories of depressive disorders. PMID- 1754657 TI - Stability of positive and negative symptom constructs during neuroleptic treatment in schizophrenia. AB - To assess the structural stability of positive and negative symptom ratings, we rated 40 schizophrenic inpatients on the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS) at medication-free baseline and after 4 weeks of neuroleptic treatment. Positive symptom variables consisted of six BPRS items, and the negative symptom variables consisted of the five SANS subscale global scores. On principal components analysis, a three factor, oblique-rotated solution resulted, with a negative symptom factor, a positive symptom factor, and an unstable behavioral agitation factor. The pre- and posttreatment factor loading patterns were similar. The findings suggest that BPRS-positive symptom items and the SANS measure distinct clinical dimensions and that the construct is stable, as demonstrated by minimal structural change with time. PMID- 1754658 TI - Variations in clinical decisions: a study of orthopaedic patients. AB - Three groups of patients were clinically reviewed within a new orthopaedics department: patients who were on an inpatient waiting list for surgery; new referrals from general practitioners; and patients who had been referred earlier and were awaiting an appointment for outpatient consultation. Approximately two fifths of patients who were already on the inpatient waiting list, and who had confirmed their wish to remain on it, were considered on clinical review not to require inpatient treatment. A third of patients attending for first outpatient consultations were immediately returned to the continuing care of their general practitioner and this proportion was higher (47%) amongst patients who were waiting for outpatient appointments and who had not been referred to a named hospital consultant. These findings draw attention to the possible inappropriate use of specialist hospital facilities because of clinical decisions taken by some general practitioners and also to variations in the threshold for surgical intervention used by hospital consultants. It is important that the medical profession develops a consensus approach to the clinical management of patients with common conditions. It is also important that clinical review of patients on inpatient waiting lists, especially those who have been waiting a long time, becomes a routine part of waiting list management. Under the new British health care system, it is likely that purchasers of health care will seek to ensure that these issues are being dealt with by hospitals with which they are considering placing contracts. PMID- 1754659 TI - Hospital and other influences on the uptake and maintenance of breast feeding: the development of infant feeding policy in a district. AB - Hospital practices in the post-natal period are now recognised as one of a wide range of influences affecting the success of breast feeding. A study of 48 non medical maternity unit staff and 250 recently delivered mothers at a District General Hospital was carried out in order to identify obstacles and sources of support in the establishment and maintenance of breast feeding. This study formed part of an evaluation of local policy development which included the appointment of a Baby Feeding Adviser. Eighty-two percent of mothers (95% confidence interval; 87.0-96.4) began breast feeding, and this fell to 57.4% (50.6-64.2) at 6 weeks. A majority of mothers reported that advice was at least partly conflicting, and of those who began breast feeding 92.7% had used supplements within 2 days. In multivariate analysis, factors significantly associated with a lower rate of initial breast feeding were: non-attendance at antenatal classes, Caucasian ethnicity, social class and religious denomination. Social factors were much less important in the maintenance of breast feeding, but mothers who had undergone Caesarian section were more likely to give up breast feeding by 6 weeks. The reported quality of advice and support from the hospital and community were not associated with the maintenance of breast feeding. Many of the maternity unit midwifery staff reported inadequate time for discussion of feeding with mothers. Although two-thirds of the staff felt that there should be an infant feeding policy or were not sure, most of those favouring a policy felt that it should not actively promote breast feeding. Their main reason for this view was the fear of inducing guilt in bottle-feeding mothers. The social and service related factors associated with the initiation and maintenance of breast feeding may be useful for targeting additional support for some mothers. The ambivalence and concerns among maternity unit midwifery staff about promoting breast feeding must be addressed if successful policy implementation is to be achieved. Plans for implementing change and evaluation are described. PMID- 1754660 TI - Neuromuscular impairment: a major cause of non-syncopal falls in elderly Chinese. AB - A survey was conducted on 138 residents in Old Age Hostels and 217 subjects living at home. Twenty-five percent of women and 12% of men reported one or more non-syncopal falls in the previous year. Neuromuscular impairment, which included knee pain, a positive Romberg sign, an abnormal gait and use of walking aids, was the main risk factor for falls in this population. Screening and preventive programmes may be based on these findings. PMID- 1754661 TI - Incidence of falling injuries leading to medical treatment in the elderly. AB - The incidence of falling injuries leading to medical treatment was described by sex, age, marital status, education, amount of daily motion, self-perceived health, mechanism of fall and severity of injury. Material was collected regarding persons aged 65 years or over seeking medical treatment due to a fall during a period of one year. Altogether 3.8% of the elderly population (men: 2.5%; women: 4.4%) sought medical treatment due to a fall at least once during this year. When repeated falls were taken into account, the total incidence rate was 5.5 per 100 persons per year. The cumulative incidence rate (percentage of persons seeking medical treatment due to a fall) of women was higher than that of the men and in both sexes it increased with age. It was also higher for unmarried, widowed or divorced persons than for married ones, and higher in less educated persons than in better educated ones. It was also higher in persons with a low amount of daily motion or poor self-perceived health than in persons with a moderate or high amount of daily motion or good health status. The multivariate analyses based on log-linear models showed two-term interactions. A low amount of daily motion, poor self-perceived health and high age were independently related to the occurrence of a fall leading to medical treatment in both sexes. PMID- 1754662 TI - The health of Travellers' children in Northern Ireland. AB - A study was carried out to examine aspects of the health status of children from a group of 'travelling people' in Northern Ireland. A total of 350 children, aged under 16 years, were included in the study. Data were gathered by community health doctors and health visitors using a standardised questionnaire. The study revealed that this community has a high degree of consanguinity and points to higher levels of congenital abnormalities than in the settled community. Uptake of immunisation was less than the settled community and hospital admissions in the younger age group were particularly due to infectious diseases. The authors conclude that provision of health services for travelling people in Northern Ireland should be urgently reviewed with consideration of the needs and lifestyle of this group. The provision of suitable sites for travelling people with adequate water and sewage facilities to reduce potential risks to health is also advocated. PMID- 1754663 TI - Management of childhood obesity through a school-based programme of general health and nutrition education. AB - A school-based nutrition education programme aimed at the control of coronary risk factor rise during childhood was started in 1983 for 150 boys and girls aged 6-7 years. The study was performed in a rural area of central Italy, where adult obesity represents a major health problem. Preventive treatment was based on general health education in schools towards healthy lifestyles. Nutritional intervention was mainly focused on the adoption of the 'prudent diet'. School teachers received specific training on how to teach 'good nutrition'. The nutrition curriculum was taught by teachers throughout the school year. Several meetings were organised to actively involve the children's parents. Practical recommendations for changes in food selection and preparation were also given. After a five-year follow up, a strong 'tracking phenomenon' for body mass index was observed, suggesting a great stability over time of lifestyles and dietary habits leading to the development of obesity during childhood. We conclude that a school-delivered programme of general nutrition education for the control of risk factors does not appear to be able to control child obesity. PMID- 1754664 TI - How schools perceive the school health service. AB - An awareness by health professionals of changing priorities facing the School Health Service (SHS) has led to increased attempts to evaluate current practice. In the present study we set out to examine how schools perceive the SHS, to identify their concerns and obtain their suggestions for improvements. Despite direct and repeated personal communication, only 26 questionnaires were returned out of 64 sent to primary and post primary schools. The majority of responses indicated a lack of knowledge about the various aspects of the SHS and a request for more information. Half the questionnaires indicated dissatisfaction with the current SHS--particular problems identified were poor communication, lack of information and inability to deal with social problems. Suggestions made by schools to improve the SHS include improved communication between schools, SHS and parents, better and increased health education. Schools identified the current health needs of pupils as health education; social, family and behavioural problems; and developmental problems. Overall those schools who responded welcomed the approach from the SHS. PMID- 1754665 TI - Percutaneous multiple puncture method of administering BCG vaccine. PMID- 1754666 TI - The natural history of low grade non-Hodgkin's lymphoma and the impact of a no initial treatment policy on survival. PMID- 1754667 TI - The pattern of rheumatoid arthritis in West Africa and comparison with a cohort of British patients. AB - Inadequate information is available on the care burden and severity of rheumatological diseases such as rheumatoid arthritis in West Africa. We therefore studied patients with rheumatoid arthritis presenting to a rheumatology unit in Nigeria and compared these with patients presenting to a British rheumatology unit. The West African patients were younger at onset of disease, less frequently had a family history, showed fewer extra-articular features and erosions and were less commonly rheumatoid factor positive. The overall mildness of the disease in the West Africans was striking. PMID- 1754668 TI - Frequency of asymptomatic hepatitis types B and C in an inner city community and relation to possible risk factors. AB - The frequency of asymptomatic carriage of the hepatitis virus types B and C in an inner city area (South London) was assessed in a survey of 1002 subjects attending their General Practitioner for minor, non-hepatic complaints. Ten subjects were seropositive for hepatitis B surface antigen (HBsAg) (1 per cent), but only one, who declined liver biopsy, had any clinical laboratory evidence of hepatitis B virus-related chronic liver disease. Carriage of, and exposure to, hepatitis B virus was significantly more frequent among people born outside the UK/Eire and those with a history of jaundice. Among people of Caribbean origin the frequency of hepatitis B virus markers fell from 31 per cent among those born in the Caribbean to 11 per cent amongst second generation subjects born in this country. Despite careful counselling, offers of further investigation and treatment of those affected, and vaccination of vulnerable children or partners, were often declined. Four percent of the same population had antibodies to the hepatitis C virus using the Ortho anti-hepatitis C virus enzyme-linked immunosorbent assay but this figure fell to 0.9 per cent when a second test, based on synthetic peptides rather than a recombinant antigen, was used. None had any abnormality of standard liver function tests. Chronic asymptomatic carriage of hepatitis, particularly in inner city areas, may be more common than previously recognized. Effective use of antiviral agents and vaccination will be limited until appropriate health education dispels the widespread misconceptions and fears associated with a diagnosis of chronic viral hepatitis. PMID- 1754669 TI - The natural history of low grade non-Hodgkin's lymphoma and the impact of a no initial treatment policy on survival. AB - The natural history of low grade lymphoma and the influence of a 'no initial treatment' policy on survival were studied retrospectively in a group of 153 patients with stage II-IV low grade non-Hodgkin's lymphoma. The median follow-up was 85 months (range 45-229 months) and median survival of 50 months (range 14 220 months). Favourable outcome was significantly associated with the absence of B symptoms and a centroblastic/centrocytic (cb/cc) diffuse and follicular histological subtype and was inversely associated with increasing age. No significant differences in survival were found according to patient gender, site or stage of disease or whether the patients were participants in a clinical trial. Importantly, there was no survival disadvantage amongst the 56 patients who were initially untreated compared to those receiving other treatment modalities: initially untreated patients had a median survival of 75 months; 56 per cent were alive at 5 years and the median treatment free interval was 33 months. This favourable outcome persisted even after adjustment for other important prognostic variables. Further studies are needed to identify the characteristics of those patients with indolent disease in whom treatment may be deferred without adversely affecting survival. PMID- 1754670 TI - Children with atopic eczema. I: Clinical response to food elimination and subsequent double-blind food challenge. AB - The role of foods in the exacerbation of atopic eczema was studied by offering a food elimination diet and subsequent random order, double-blind food challenges to 91 eczematous patients, [49 males and 42 females, median age 4.5 years (range 0.5-15)]. Eczema improved in 49 of 66 (74 per cent) (skin score fall greater than or equal to 3) after stopping cows' milk, eggs and various other foods, with significant decreases in erythema, excoriation, lichenification and extent of eczema. One hundred and ninety-four food challenges were given to 64 patients who had shown objective or subjective improvement. Eczema and associated symptoms were significantly worse after cows' milk and tomato compared with placebo. Egg did not worsen eczema, but 48 per cent of 44 challenges were incomplete, mainly due to hypersensitivity reactions and challenge refusal. The longer a food had been avoided, the less likely was the chance of a positive food reaction. Clinical history did not predict response to dietary manipulation. A standard elimination diet avoiding cows' milk, egg, tomatoes and possibly colours and preservatives should help up to three-quarters of patients, and is easy to implement with the help of a dietician. This diet may be considered in all children with moderate or severe eczema. PMID- 1754671 TI - Children with atopic eczema. II: Immunological findings associated with dietary manipulations. AB - A group of 91 children with atopic eczema entered a study where clinical and immunological features were compared before and after a food elimination diet, and after double blind randomized food challenges in which a food was given for several days at a time. Eczema improved significantly during the diet and became worse on food challenges. The clinical outcome of food elimination could not be predicted by the initial skin prick test results, serum immunoglobulins, total or food-specific IgE, or complexed IgG or IgE. There was a tendency for patients whose eczema did not improve after food elimination to have higher initial serum IgG levels, without a corresponding increase in skin infections. The radioallergosorbent test to soy gave a higher result in those who improved on diet. No significant changes in serum or complexed immunoglobulins occurred over the period of food elimination or subsequent food challenge. Results of food challenges could not be predicted by initial serum immunoglobulin levels. A history of spring/summer exacerbations of eczema correlated with positive skin prick tests to silver birch pollen, but not to grass pollen. Serological tests did not help in planning food diets in atopic eczema, and the immunological studies did not delineate any particular mechanism by which foods might exacerbate eczema. PMID- 1754672 TI - Glucose counter-regulation in health and disease: current concepts in hypoglycaemia recognition and response. PMID- 1754673 TI - Long-term survival after resuscitation from ventricular fibrillation occurring before hospital admission. AB - Factors related to long-term (post-discharge) outcome following successful resuscitation from pre-hospital ventricular fibrillation by a physician-manned mobile coronary care unit were studied. Between 1 January 1966 and 31 December 1987, 190 patients were resuscitated from pre-hospital ventricular fibrillation (158 male; mean age 56 years). The aetiology of ventricular fibrillation was acute myocardial infarction in 131 patients (69 per cent), ischaemic heart disease without infarction in 48 (25 per cent) and other or unknown in 11 (6 per cent). Predicted actuarial survival rates at 1, 2, 5, 10 and 20 years were 76 per cent, 66 per cent, 41 per cent, 27 per cent and 12 per cent respectively. Of 128 recorded deaths over 20 years, 85 per cent were cardiac and 48 per cent were defined as sudden death outside hospital. Factors significantly associated with increased long-term mortality (p less than 0.05), based on analysis of 10 year actuarial life tables using the Lee-Desu statistic were ventricular fibrillation due to ischaemic heart disease without infarction rather than acute myocardial infarction, a history of previous myocardial infarction, a history of hypertension, digoxin and diuretic therapy before ventricular fibrillation and digoxin as discharge medication, and failure to stop smoking after discharge from hospital by patients who had been smoking prior to ventricular fibrillation. In addition, Cox's regression analysis showed that patient age greater than or equal to 60 years was significantly associated with increased long-term mortality. On multivariate analysis, factors independently associated with increased long-term mortality were ventricular fibrillation occurring before 1977, previous myocardial infarction or hypertension and digoxin as discharge medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754674 TI - Acute cerebrovascular episodes in systemic lupus erythematosus. AB - Twelve patients with systemic lupus erythematosus (SLE) who developed major acute cerebrovascular episodes are described. All patients were female, with a mean age of 43.3 years and they had suffered from SLE for between 1 month and 22 years (mean 9.3 years) at the time of stroke. All patients had multiple clinical and laboratory features of systemically active SLE. Stroke was the initial neurological feature in nine patients. Cerebral infarction was confirmed in eight patients and cerebral haemorrhage in two; the two remaining patients had convincing clinical evidence of thromboembolic neurological complications. Characteristic clinical and serological features of antiphospholipid antibodies were observed in six patients (50 per cent). Five patients died as a direct result of stroke and two other patients died within one year. PMID- 1754675 TI - Bites by the king cobra (Ophiophagus hannah) in Myanmar: successful treatment of severe neurotoxic envenoming. AB - Three patients bitten by the world's largest species of venomous snake, the king cobra (Ophiophagus hannah), were observed in Myanmar (Burma). All three were involved in the famous snake dance in Yangon (Rangoon) Zoological Gardens. One patient showed no signs of envenoming despite a sustained bite, another developed only signs of local envenoming, but in a third there was severe neurotoxic envenoming requiring mechanical ventilation for 64 1/2 hours, episodes of hypotension and massive swelling of the bitten limb. This patient showed some signs of recovery before delayed treatment with specific antivenom. It is possible that all three patients had some immunity to king cobra venom resulting from traditional 'immunization' achieved by scratching venom into the skin. The literature on king cobra bites is reviewed and recommendations given for antivenom and ancillary treatments. PMID- 1754676 TI - Prevalence of persistent cough during long-term enalapril treatment: controlled study versus nifedipine. AB - The prevalence and severity of cough during long-term enalapril treatment were examined by comparing a cohort of 136 hypertensive patients who started treatment with enalapril with consecutive age and sex-matched patients who commenced nifedipine therapy during the same period. Cough and other symptoms were assessed by a questionnaire designed to avoid bias towards reporting cough. After a mean of 27 months' treatment patients on enalapril had an excess of persistent cough (16 per cent, 95 per cent CI 7-25, p less than 0.01), voice change (14 per cent, 95 per cent CI 2-27, p less than 0.05) and sore throat (10 per cent, 95 per cent CI -0.1 to 20.3 per cent, p less than 0.01) when compared to nifedipine-treated patients. The cough was usually dry, moderate or severe, paroxysmal, and troublesome at night. Cough tended to be more common in women (23 per cent vs. 7.2 per cent), non-smokers, and at higher doses of enalapril, but was not related to age, duration of treatment, or chronic respiratory disease. Dry cough commonly persists as a troublesome side-effect during long-term enalapril treatment, and is often associated with voice change and sore throat. PMID- 1754677 TI - Massive cystic hepatomegaly in a female patient with polycystic kidney disease treated by combined hepatic and renal transplantation. AB - A patient with cystic kidney disease of adult onset and severe cystic hepatomegaly is presented. The patient was severely disabled solely by her abdominal bulk. Simultaneous liver and renal transplantation was undertaken successfully. PMID- 1754678 TI - [MR tomographic diagnosis of internal derangement of the temporomandibular joint]. AB - On the basis of MR imaging studies in 150 temporomandibular joints (TMJ) a classification system for internal derangement of the TMJ was defined. Clinically, internal derangement is characterized by disc displacement and disorders of the mandibular condyle. MR imaging enables a differentiation of early stages (I,II) with disc displacement, the intermediate stage (III), and the later stages (IV,V) with osseous destruction. Optimal diagnostic results (n = 140) allowed the use of proton-density sequences in both open and closed joint positions (TR/TE = 1000/28). Dynamic imaging of the TMJ was performed using fast gradient echo sequences and a self-developed hydraulic opening device (n = 20). MR imaging has proved to be the method of choice for the pre- and post therapeutic evaluation of internal derangement of the TMJ. PMID- 1754679 TI - [The diagnostic reliability of the occipitomental radiograph of the paranasal sinuses. Correlation with magnetic resonance tomography]. AB - 100 conventional occipitomental radiographs of the paranasal sinuses were studied independently by five radiologists. Predictive values were determined, based on MRI as the gold standard. Sensitivity and specificity for detection of mucosal thickening in the sinuses were: maxillary sinus: 0.73/0.76, frontal sinus: 0.20/0.85, ethmoid sinus: 0.38/0.87, sphenoid sinus: 0.14/0.96. In the maxillary sinus polypoid thickening was demonstrated with a significantly higher sensitivity than that of diffuse mucosal thickening (0.82 versus 0.65, Chi-square test, p less than 0.01). Because of the low predictive values the occipitomental view is insufficient to assessing mucosal thickening in the paranasal sinuses, with the exception of polypoid mucosal thickening in the maxillary sinus. PMID- 1754680 TI - [Diagnostic imaging of the salivary glands in children and adolescents]. AB - In children and adolescents, imaging of the salivary glands is a valuable supplement to clinical examination in various diseases. The choice of the most appropriate radiological technique depends on patient compliance, the necessity of avoiding radiation exposure as far as possible, and the tentative diagnosis made on the basis of the clinical examination. Ultrasonography (US) is the method of choice for the detection of both acute inflammatory disease and masses in the salivary gland and the adjacent tissue. US can also be implemented as a screening method for calculi, though sialography is superior for this purpose. Sialography is the only technique that allows diagnosis and evaluation of the degree of chronic inflammation. Computed tomography and magnetic resonance imaging are required for more deeply located neoplasms of the parotid region. PMID- 1754681 TI - [Localized proton MR spectroscopy. A non-invasive insight into brain metabolism]. AB - Recent progress in image-controlled, localized proton MR spectroscopy offers a non-invasive means of gaining unique insights into brain metabolism in man. Combined studies with MR imaging can be performed within about 1 h. Results obtained in healthy subjects provide the basis for reliable identification and quantification of metabolite concentrations in the CNS and allow determination of their regional variability and age dependence. Clinical applications include infarcts, tumors, and neurodegenerative diseases, and also metabolic disturbances resulting from diseases of the internal organs, such as diabetes mellitus or liver cirrhosis. PMID- 1754682 TI - Peripheral upper lobe collapse simulating pleural effusion. AB - Two cases of segmental collapse of the upper lobe simulating an apical pleural effusion in association with pneumothorax are reported. Our cases differ from previously reported ones in that the peripheral collapse occurred in association with a pneumothorax without pleural adhesions, it was segmental rather than lobar, and was observed in adults. PMID- 1754683 TI - [A calcified coronary artery aneurysm following Kawasaki syndrome]. AB - On the chest X-ray of a 15-year-old patient, a round, egg-shell-like calcification was seen in projection into the left heart border. This finding was caused by a calcified coronary aneurysm following Kawasaki's disease. Although this has been described as a typical change, it is rarely found in daily clinical routine. PMID- 1754684 TI - [MR imaging of a giant solitary trichoepithelioma of the skin]. AB - Magnetic resonance images of a "giant solitary trichoepithelioma" (GST) are presented for the first time. Furthermore, to our knowledge this is the largest GST ever to be reported in the current literature. Magnetic resonance imaging gave information on the origin of the tumor and on the depth of invasion. The signal intensity is non-specific and does not allow histological classification. Preoperatively, the MR examination depicts the extent of the tumor and thus helps in the surgical management that follows. PMID- 1754685 TI - [An unclear abdominal tumor. Non-Hodgkin lymphoma of the small intestine, Burkitt type, Musshoff stage II.1]. PMID- 1754686 TI - [A bladder tumor following pancreas transplantation? Intravesical necrotic material in transplant pancreatitis]. PMID- 1754687 TI - Generalization and specialization in artificial neural networks. PMID- 1754688 TI - Stereology: a method for analyzing images. AB - This review deals with notions of shape, sizes, numbers, densities and orientation in space, all basic concepts in stereology. With the initiation by Delesse in 1847, but mainly since the beginning of the XXth century, many stereological methods have been published allowing us to relate two-dimensional measurements easily obtainable on flat histological images with three-dimensional characteristics of the structure analysed. Looking at these methods, the neurobiologist, generally impermeable to concepts of sampling, statistical bias, efficiency, cost of effort and distribution-free, is discountenanced and continues old laboratory usages and customs. Furthermore, for the last ten years, the advent of a plethora of new powerful tools, considered as assumption-free and more efficient than the previous ones, increase the risk proportionately the disarray of the potential user. The purpose of this review is to present synthetically all traditional and actual aspects of stereology in order to guide the reader in the labyrinth of this speciality. The necessarily short exposition is compensated by many references to which the beginner or the initiated can refer. PMID- 1754689 TI - [Sigmund Freud--portrait of writer]. AB - As physician and writer Freud held an ambivalent attitude towards poets. Jens clarifies this by reference to Wilhelm Stekel's address and the subsequent discussion in Freud's Wednesday evening society, both concerned with the world premiere of Gerhart Hauptmann's stage play Griselda (1909). PMID- 1754690 TI - [Freud's interpretation of the manifest dream. Attempt at theoretical historical and biographical motives of ambivalent dream devaluation]. AB - Freud's description of the manifest dream is characterized by an implicit appreciation and an explicit devaluation of dream images. The theoretical motives for this ambivalent evaluation are, according to the author, already apparent in Freud's primacy of the written word evident in his preanalytical writings, which submit dream images to the standard of the written word and therefore devaluate them. According to the author the underlying biographic motive is an ambivalent internalization of the jewish law that prohibits the creation of idols which was conveyed to Freud by his father and the Philippson Bible. PMID- 1754691 TI - [Schopenhauer as the originator of Freudian metapsychology]. AB - The influence of 19th century philosophy on Freud's thought is to this day underestimated in comparison with the influence of the scientific theories. Godde vindicates Max Horkheimer's proposition that Freud was "in certain respects a successor to Schopenhauer" even though Freud knew Schopenhauer (and Nietzsche) through secondary literature rather than through the original writings. PMID- 1754692 TI - [Oroantral communication and its treatment]. AB - The most frequent cause of an oroantral perforation is the extraction of an upper molar. In this article, this for a dental practitioner important entity is discussed in detail. After the etiopathology, clinical and roentgenological diagnosis is discussed. As 6.5% of perforations closes spontaneously, the question is raised wether all perforations should be surgically treated. Those different surgical techniques are then described and emphasis is thereby laid on the difference between a mere perforation and a fistula. PMID- 1754693 TI - [Lingual nerve injury during extraction of lower wisdom teeth]. AB - A lingual nerve injury is an infrequent but unpleasant complication of the removal of lower third molars. The nerve stays at risk even with a correct technique. The classifications of nerve injuries of Seddon and Sunderland give insight in the complexity and give guidelines for prognosis and treatment. Degeneration and regeneration as in other peripheral nerves occur also here and knowledge of these phenomena is crucial for the success of the microsurgical repair. Confronted with the problem, an attempt to a correct evaluation of the extent of the injury should be done, and transfer to a specialist is necessary when the dysesthesia is still persistent after more than 2 months. PMID- 1754694 TI - [Complications of osteotomies]. AB - The authors wish to present a review of the literature on complications in orthognathic surgery. They are classified into non-specific, general complications and into complications which are specific, according to the region the osteotomy is performed in. Though the list of possible complications is very extensive, one should realise that they are often based on single case-reports and that orthognathic surgery in general should be considered as a group of safe technical, surgical procedures. PMID- 1754695 TI - [Subcutaneous emphysema of the oral floor during cleaning of a bridge fixed on an IMZ implant. Case report]. AB - A case of subcutaneous emphysema following intraoral elimination of plaque and tooth shading, on a bridge fixed on implants, is presented. An instrument that produces a cleaning spray with a water-air-powder mixture was used. A few minutes after this cleaning procedure there was facial swelling. The patient experienced difficulties in breathing and in swallowing; symptoms of unilateral hearing loss were also noticed. The emphysema lasted for three days. Etiology, diagnosis, differential diagnosis, complications and management are discussed. PMID- 1754696 TI - [Prevention of caries and of osteoradionecrosis in patients irradiated in oncology]. AB - Dental lesions following radiation therapy of the head and neck cancers are known for a long time, and the role of a decreased salivary function in the induction of radiation caries has been recognized by Del Regato in 1939. The salivary glands are most frequently included in the radiation fields for the treatment of lesions of the upper aero-digestive tract; they are also irradiated, in variable proportion, in other conditions such as Hodgkin's disease. From a clinical point of view, the dental caries observed after radiation therapy are diffuse and rapidly evolutive. However, from a histological point of view, they are similar to the current type of dental caries. Daily application of fluoride has been shown to prevent the appearance of the caries and of the related osteo radionecrosis. The experience of the Cancer Centre Georges-Francois Leclerc of Dijon is reported and especially the results of randomized prospective studies concerning the efficiency of the fluoride prevention. Taking into account the available clinical experience, it seems reasonable, at present, to state that preservation of teeth, in irradiated patients should be the rule and not the exception, given good dental conditions prior to the treatment and patient collaboration. The 5 minutes daily application of fluoride gel is the most reliable method for prevention of post-irradiation dental caries. The twice daily use of high-content fluoride tooth-paste is a good alternative, provided its limitations are well understood by the clinician and the patient. The systematic use of high-content fluoride tooth-paste for the prevention of caries in the general public is discussed. PMID- 1754697 TI - [Dental care phobia: example of genetically-programmed learning?]. AB - Out of a sample of 2,000 patients, one group was identified whose fear of dental care presented all the characteristics of phobia. This phobia seems to be linked to the pain of previous dental care. Following our hypothesis, it would not be a pathological state, but rather a particular example of genetically programmed learning. PMID- 1754698 TI - [Dental care for patients being treated with oral anticoagulants. Prevention of hemorrhagic complications]. AB - The oral management of patients receiving oral anticoagulants is controversial, especially concerning oral surgical procedures. The clinician has to balance the risk of reducing or stopping the medication with that of triggering bleeding complications. For each individual patient and for each dental intervention, two important factors should be evaluated and balanced: the risk for bleeding complications represented by the dental intervention and the medical risk for the patient in case of interruption of the anticoagulant therapy. Practical instructions for the different types of dental interventions and medical risk categories are proposed. PMID- 1754699 TI - A case-control study on alcohol consumption and the risk of chronic liver disease. AB - We carried out a hospital based case-control study involving 655 patients with chronic liver disease encompassing chronic hepatitis, asymptomatic liver cirrhosis and symptomatic liver cirrhosis and 655 pair-matched control individuals in order to estimate the dose-response relationship between alcohol consumption and the occurrence of chronic liver disease. Alcohol intake was measured by a questionnaire and expressed as Daily Alcohol Intake (DAI) during the patient life. DAI estimates from patient interviews were in good agreement with those obtained by interviewing a sample of relatives. We found an exponential positive association between DAI and the risk of chronic hepatitis and cirrhosis. However, consuming less than 100g of alcohol every day did not increase the risk of developing chronic liver disease. For asymptomatic cirrhosis the risk was lower than for chronic hepatitis, especially at high DAI, probably because high consumption carried a high probability of liver decompensation. For symptomatic cirrhosis, the risk function showed a similar pattern as for chronic hepatitis. Chronic hepatitis patients were 6-7 years younger than cirrhotics. Our results suggest that the evolution towards cirrhosis once a chronic liver damage has occurred is probably time-dependent, but not or minimally dependent on alcohol intake. PMID- 1754700 TI - [Socioecological determinants of the risk of accidents in young pedestrians]. AB - We studied all traffic accidents to pedestrians under age 15 which occurred on the Island of Montreal during an eighteen months period. Data were collected from eleven hospitals and completed with accident police records. A spatial quadrat analysis, a Comparative Accident Index, and a comparative analysis of the means of different socio-ecological variables between high and low risk accident areas revealed interesting patterns. The location of traffic accidents is not random but rather presents a particular spatial structure. High risk zones are characterized by dense population, fast-moving traffic, and the absence of parks. Accidents often take place on two-way streets, far from traffic lights, on dry surfaces, in good weather, and with good visibility. The socio-economic status of the victim's family as measured by education, income, and unemployment, tends to be low. More boys than girls are victims. Children are often injured while getting out of a car or crossing unconventionally. PMID- 1754701 TI - [Assessment of costs of health insurance, substitution therapy in chronic renal insufficiency]. AB - The authors have studied the cost of the different treatments proposed in ESRD to patients attended by the same nephrologic team. For each patient they have isolated two consecutive periods of treatment, each six months apart. Treatment modifications noted between the two periods allowed the patient to be used as his own control. The results show that the costs are essentially composed of the dialysis sessions, hospitalisations and transport, and that their level and composition differ significantly between the different treatments. They derive a typology composed of three groups of patients, which differ in their treatment, age, duration of ESRD, complications, and total cost of treatment. They conclude that services should be organised in such a way that a range of different treatments can reasonably be provided, according to patient needs. PMID- 1754702 TI - [Interim analysis in therapeutic trials: a brief survey of current developments]. AB - It is often interesting to introduce, in the plan of a clinical trial, the possibility to make interim analyses. However, this induces an increase of type one error and it is thus necessary to use appropriate statistical methods. Usual group sequential procedures are mentioned, just as more recent approaches like flexible methods with free number and time of analyses, or like the succession procedure. PMID- 1754703 TI - [Parkinson's disease and environmental factors]. AB - The etiology of the nigrostriatal pathway degeneration in Parkinson's disease (PD) is unknown but there is a growing pool of evidence that environmental factors may be involved in the genesis of this disorder. The discovery of the N Methyl 4-Phenyl 1,2,3,6-Tetrahydro-Pyridine (MPTP)-induced injury in late 1970s provided the first experimental model of PD and stimulated dramatically the epidemiological research. An excitotoxic amino acid contained in Cycadales, which is thought to be responsible for the amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam, provides another example of toxin-induced parkinsonism. This amino acid is present in most seeds common in the Western diet. In developed countries, prevalence of PD is 2 to 5 times as high than in developing countries. PD patients in developed countries are more likely than controls to have lived in rural environment. Case control studies have suggested that this positive association is possibly related to pesticides and herbicides exposures or well water drinking. Dietary surveys are now going on and several hypothesis are tested including high MPTP-structural analogs or seeds consumption in PD patients and low antioxidants consumption. The negative association between smoking habits and PD has been recognized for more than 20 years. There is evidence that this association is not an artefact due to the disease affecting smoking habits. Its origin is unknown but it could provide important aetiological clues for PD. The most recent hypothesis concerning the relationships between these environmental factors and PD are reviewed and pertinent suitable surveys for the future are discussed. PMID- 1754704 TI - [Patient compliance in ambulatory medical care]. AB - During February and March 1987, 313 private practitioners and 35 outpatients clinics in the cantons of Vaud et Fribourg participated in the study "Ambulatory medical practice". A representative sample of more than 17,800 records was collected and analysed from the 110,000 weekly consultations. In this paper we discuss the patient flow in ambulatory medical care. Overall, patient flows appear to be influenced more by practitioner and patient characteristics than by contextual factors such as medical density. In private practice the proportion of patients who are appointed and indeed attend the consultation is 50%; in outpatient clinics only 30%. The patient's compliance (probability of keeping an appointment) depends on one hand of the physicians' specialty and, on the other hand, it decreases when the appointment rate increases. PMID- 1754705 TI - [Proportion of cases attributable to public health: definition(s), estimation(s) and interpretation]. PMID- 1754706 TI - [Survey methodology in the prevalence of Alzheimer's disease in the Rhone delta]. PMID- 1754707 TI - [Sea bathing and risk of infection: a case-control study in the coastal area of Pas-de-Calais]. PMID- 1754708 TI - The alcoholic habit in the spanish hospital environment. PMID- 1754709 TI - Molecular genetics of the K end of the murine MHC. AB - A systematic search of cloned DNA from the region between the Pb (A beta 3) and Ob (A beta 2) genes of the murine major histocompatibility complex (MHC) has revealed the presence of at least seven new genes. Three of these genes show significant similarity to MHC class II antigens. Two of the other genes are members of a superfamily of transport protein genes and are believed to function in the transport of antigenic peptides during antigen processing. Genes encoding at least two subunits of a large intracellular protein complex (the LMP complex) that is believed to be involved in antigen processing were previously mapped to the same genetic region. This data suggests that this region of the MHC contains, in addition to MHC class I and class II genes whose products provide the scaffolding for antigen presentation, a cluster of genes required for antigen processing. PMID- 1754710 TI - Transcriptional regulation of HLA-DRA gene. AB - Transcriptional regulation of class II genes is complex. DRA, for example, is expressed in both tissue-specific and lymphokine-inducible fashion. High levels of expression in B and activated T cells depend upon a lymphoid-specific transcriptional enhancer located in the first intron and on the upstream and downstream promoter elements. Conserved upstream promoter Z and X sequences (CUS) are the main determinants of this complex regulation. At least four distinct trans-acting factors that might be differentially expressed in various cell types bind to these Z and X boxes. These are members of JUN, helix-loop-helix (HLH), C/EBP and ETS families of proteins. PMID- 1754711 TI - Crystallization of HLA-DR antigens. AB - The class II major histocompatibility antigens HLA-DR1, DR2, DR3, DR4, DR7 and DR8 were purified by immunoaffinity chromatography from homozygous human B lymphoblastoid cell lines. The purified, detergent-soluble molecules were cleaved with the protease papain to remove the hydrophobic transmembrane regions and cytoplasmic tails. Crystals were obtained for each of the papain-solubilized fragments. DR1 crystallized under a variety of different conditions, resulting in two different orthorhombic crystal forms, one of which diffracts as far as 3.5A. Crystals of DR2, DR3, DR4 and DR8 have the same unit cell dimensions as the DR1 crystals, and crystals of DR3 and DR4 have the same diffracting power as the DR1 crystals. The best DR7 crystals obtained thus far are hexagonal and diffract to only about 8A. Crystals of similar hexagonal form have also been observed for most of the other DR subsets. PMID- 1754712 TI - Expression and characterization of recombinant mouse beta 2-microglobulin type a in insect cells infected with recombinant baculoviruses. AB - The murine beta 2-microglobulina cDNA was cloned into pAc373 and pVL941 transfer vectors and introduced via homologous recombination into the genome of Autographa californica nuclear polyhedrosis virus downstream of the polyhedrin promoter. Both types of recombinant baculoviruses were isolated and used to infect Spodoptera frugiperda (Sf9) lepidopteran cells. beta 2m was synthesized at a substantially higher rate in cells infected with the pVL941-derived virus than when the pAc373-based virus was used. beta 2m was secreted into the culture medium where it accumulated and, under the best conditions, reached an approximate level of 10 micrograms/10(6) cells. Pulse-chase experiments after metabolic labelling with 35S-methionine followed by immunoprecipitation showed that beta 2m was stable, but that the secretion process in infected cells was relatively slow. Recombinant beta 2m was endowed with biological activity and was indistinguishable from that produced by mouse cells in 2D gel analysis. beta 2m was purified to near homogeneity from serum-free culture medium conditioned by recombinant baculovirus-infected cells by using an immunoaffinity column. The use of the insect cell/baculovirus expression system should constitute a suitable source of mouse beta 2m and should aid experiments aimed at unraveling its interactions with mouse class I histocompatibility molecules. PMID- 1754713 TI - Distinct mechanisms of peripheral tolerance in transgenic mice. PMID- 1754714 TI - Influence of antigen processing on thymic T-cell selection. AB - The design of a specific blocking peptide for the immunosuppressive therapy of an autoimmune disease requires the identification of peptides of an autoantigen that are physiologically processed in vivo and bind to MHC-encoded membrane glycoproteins. However, knowledge of how an antigen is physiologically processed by antigen-presenting cells (APC) in vivo, particularly in the thymus, is lacking. It is also unknown whether the processing of an antigen by different APC in the thymus can influence thymic T-cell selection. This is an important consideration for attempts to delete or inactivate autoreactive T cells that elicit autoimmune disease. To address these issues, we investigated the processing of biosynthetically labelled recombinant human insulin (rHI), a model autoantigen, injected into mice and characterized the insulin peptides associated with MHC class II molecules on thymic epithelial cells and dendritic cells. These APC were found to differ in the way they process insulin. The detection of MHC class-II-bound insulin peptides on the surface of the epithelial cells but not the dendritic cells correlated with their capacity to either present or not present insulin to T cells, respectively. Thus, antigen processing may control the appearance of different peptide-MHC class II complexes on thymic APC that mediate positive and negative selection, and thereby influence the development of the T-cell repertoire. Our findings could have important bearing on the future design of synthetic blocking peptides that reduce or eliminate the onset of autoimmune disease. PMID- 1754715 TI - T-cell immunotherapy of cancer. AB - In animal systems, complete and permanent eradication of tumours can be achieved by adoptive transfer of MHC-restricted T cells, combined with IL2. In certain types of human cancer (melanoma and perhaps renal cell carcinoma), tumour specific T cells are probably the therapeutically most active cells among LAK or TIL cells. To prove these points, it is necessary to conduct trials with cloned tumour-specific T cells. Other potentially immunogenic tumors are cervical carcinoma, associated with human papilloma virus, and Burkitt's lymphoma, associated with Epstein-Barr virus. Most other human tumours, caused by subtle mutations in proto-oncogenes, are likely to be poorly or non-immunogenic. It is worthwhile trying to overcome this by vaccination with IL2 or IFN gamma-producing tumour cells or by deliberate vaccination with desirable targets for tumour specific CTL such as the products of point-mutated oncogenes, including ras (Jung and Schleusener, 1991) and p53 (Rodriguez et al., 1990; Halevy et al., 1990), provided the relevant peptides are processed and bound to MHC class I molecules. Other potential targets are breakpoint peptides of translocated oncogene products such as bcr/abl (Van Denderen et al., 1990). In viral systems, it has already been established that peptide vaccination for protective CTL induction is feasible (Aichele et al., 1989; Schulz et al., 1991; Kast et al., 1991). PMID- 1754716 TI - In vivo stimulation of H-2Dd expression following RadLV infection of thymocytes: increased transcription and DNA-binding activity to sequences 5' of the Dd gene. AB - Early studies showed that resistance to RadLV-induced leukaemia is mediated by gene(s) in the H-2D region of the MHC. Furthermore, these experiments correlated disease resistance with changes in H-2 expression occurring very early after virus inoculation. In the present study, we have begun to study at the molecular level this stimulation of H-2Dd class I expression in thymocytes of resistant mouse strains following infection by RadLV. The resistant strain of B10.T(6R) mice is used in these studies. When these infected thymocytes are assayed by fluorescence-activated cell sorting analysis, we can detect increased levels of H 2Dd expression on the surface of the thymocytes as early as 12 days following intrathymic injection of RadLV. RNA was prepared and examined by Northern blot analysis; H-2 mRNA levels are shown to be elevated on the order of four-fold. Nuclei were prepared from normal and infected thymocytes and the run-off transcripts were analysed by slot-blot hybridization. The rate of H-2 mRNA transcription is shown to be two- to three-fold higher in RadLV-infected thymocytes at 14 days post-infection when compared to that of normal thymocytes. These data demonstrate that elevation of H-2 surface expression following RadLV infection is the result of transcriptional activation. Extracts have been prepared from both normal and infected B10.T(6R) thymocytes and have been used in gel mobility assays in order to detect the interaction of potential trans-acting regulatory factors with sequences 5' of the H-2Dd gene. Specific binding occurs in both extracts, but the assay shows that the extracts differ both quantitatively and qualitatively; the extracts from infected thymocytes bind to additional sequences and to a higher degree than that from normal thymocytes. DNase I protection analysis locates a number of protein-binding sites, some of which are protected by extracts of either origin and some of which are only protected by extracts from infected cells. Two of these sequences are similar to the previously recognized consensus recognition sequences for the binding of AP-1 and NF-chi B. Oligonucleotides have been synthesized for both the genomic sequences being protected from DNase I digestion as well the published consensus sequences. While the DNA-binding activity in infected thymocytes for both AP-1 and NF-chi B-binding sites is increased, the binding to the genomic "AP-1 like" binding site is activated to a considerably greater level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1754717 TI - The T-cell repertoire is not dictated by self antigens alone. AB - The influence of genetic and environmental factors on the functional cytotoxic T cell (CTL) allorepertoire was studied by comparing the CTL precursor frequencies against the same HLA alloantigens in 116 sibling pairs. A significantly different precursor frequency was found in 68%, 61% and 59% of siblings sharing 0, 1 and 2 HLA haplotypes, respectively. These data show that, although HLA is important in determining the T-cell repertoire, this is hardly reflected in the allorepertoire. Even 50% of the monozygotic twin pairs showed a significant disparity in their CTL allorepertoire, indicating that environmental factors play a role as well. The non-inherited maternal HLA antigens could be identified as one of the environmental factors shaping the CTL allorepertoire. PMID- 1754718 TI - The pros and cons of polymorphism: a brighter future for cheetahs? PMID- 1754719 TI - Towards a structural understanding of alloreactivity. PMID- 1754720 TI - Intracellular routes for antigen processing and presentation. PMID- 1754721 TI - HLA B27: a disease-associated immune response gene. PMID- 1754722 TI - Genetic analysis of a complex, multifactorial disease, autoimmune type 1 (insulin dependent) diabetes. PMID- 1754723 TI - Mechanisms and significance of HLA type I diabetes association. PMID- 1754724 TI - Limited heterogeneity of autoantigens and T cells in autoimmune diseases? AB - For many induced and spontaneous autoimmune diseases, a predominant role for T cells in the organ-specific destruction process has been shown. In one of the induced models of autoimmunity, experimental allergic encephalomyelitis (EAE), a very small heterogeneity of T-cell receptor (TcR) molecules is expressed by the pathogenic T cells in both rats and mice. Contrary to induced autoimmune diseases, little is known about the autoantigens recognized by these autoimmune T cells and the heterogeneity of their TcR in spontaneous autoimmune diseases. The aim of this work was to establish a system which allows characterization of relevant autoantigens in spontaneous insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. A completely different approach was taken to characterize the gene products of the minor lymphocyte stimulatory (Mls) loci. These gene products are responsible for the clonal elimination or the clonal stimulation of T cells expressing particular TcR V beta genes and therefore could be implicated in induction of autoimmune diseases by oligoclonal T-cell populations. The finding that Mls antigens are encoded by retroviral sequences leads to the hypothesis that viruses could be the inducing agents of autoimmune diseases. PMID- 1754725 TI - Monoclonal antibodies: probes for studying experimental autoimmunity in animals. PMID- 1754726 TI - The use of MHC-binding peptides in the immunotherapy of autoimmune diseases: a commentary. PMID- 1754727 TI - Ir genes: towards the year 2000. PMID- 1754728 TI - Microscopic analysis of arterial microsphere distribution in rabbit liver and hepatic VX2 tumor. AB - Microspheres conjugated to radioisotopes and chemotherapeutic agents are playing an important investigative and clinical role in the management of metastatic neoplasms. The purpose of our investigation was to histologically assess the basis for regional intra-arterial microsphere therapy, by comparing the spatial distribution of microspheres in the tumor and liver of experimental models of hepatic metastases. Three New Zealand white rabbits with hepatic VX2 tumor implants were arterially injected with hepatic doses of either 15 or 30 million blue-dyed, polystyrene microspheres (27 microns-diameter). Microscopic examination of random liver and tumor samples revealed that 6-12 times as many microspheres were embolized within tumor than in normal liver (p less than 0.002). The majority of microspheres aggregated into clusters of various size within liver and tumor vasculature, though analysis of cluster sizes illustrated an exponentially skewed distribution toward isolated microspheres. Approximately eight times as many clusters were observed in tumor than in liver (p less than 0.008). Finally, a morphometric analysis was used to quantitate the minimal distances separating microsphere clusters, the intercluster distance (ICD). Analysis of over three thousand intercluster measurements revealed a median ICD approximately five times lower in tumor than in liver (p less than 1 x 10(-8)). This microquantitative analysis provides a fundamental description of how regional intra-arterial microsphere therapy allows the targeted delivery of microspheres to neoplastic tissue, to potentially improve the therapeutic index in the treatment of hepatic metastases. PMID- 1754729 TI - Synthetic polymers conjugated to monoclonal antibodies: vehicles for tumour targeted drug delivery. AB - (N-(2-Hydroxypropyl)methacrylamide (HPMA)) copolymers have seen extensive development as sophisticated lysosomotropic drug carriers. They can be used for site-specific drug delivery by incorporation of appropriate targeting groups and here we report their conjugation to antitumour monoclonal antibodies (the murine IgG, antibody B72.3 and its Fab' and Fab'2 fragments) and assessment as vehicles for tumour-specific drug delivery. Conjugates were synthesised containing an average 5 copolymer units (Mw 20kD) per antibody molecule. Kinetics of elimination and body distribution of radiolabelled conjugates in mice were substantially modified compared with native antibody and fragments, showing prolonged circulation in the bloodstream. Notably, the half-time for bloodclearance of the Fab' fragment (35min) was extended ten-fold following conjugation (6h). The conjugates provoked only a low immune response in A/J mice, following three injections in adjuvant (IgG titre-1 less than 100), and were resistant (up to 50%) to proteolytic degradation by preparations of rat liver lysosomal enzymes. The parent antibody targeted efficiently to human colorectal carcinoma (LS174T) xenografts in nude mice (up to 25%/g); the conjugates, however, showed no tumour-targeting, probably due to masking by polymer chains (which are attached by non-specific aminolysis). Conjugates designed to maintain immunoreactivity following linkage through oxidised carbohydrates are currently being synthesised. Nevertheless, the conjugates display increased rates of extravasation, compared with proteins of the same hydrodynamic size, and the decreased charge is anticipated to accelerate diffusion through tumour interstitium. PMID- 1754730 TI - Effect of verapamil on the uptake and efflux of etoposide (VP16) in both sensitive and resistant cancer cells. AB - The effect of calcium antagonist verapamil on the uptake and efflux of Etoposide (VP16), a semi-synthetic derivative of podophylotoxin and a broad spectrum antineoplastic agent, has been investigated and compared in sensitive (UM-UC-2) and resistant (UM-UC-9) human bladder cancer cells, and L1210 leukemia cells, by using both radioisotope (3[H]-VP16) liquid scintillation and high performance liquid chromatography assay with electrochemical detection. The uptake of VP16 was rapid in all three cell lines, showing an initial rapid linear phase followed by a second slower phase, but at steady state the ratios of intracellular to extracellular VP16 concentrations were only 0.004-0.006. No significant difference in drug uptake was observed in sensitive UM-UC-2 and resistant UM-UC-9 cells at all concentrations studied. Verapamil at a concentration of 10 microM enhanced the intracellular VP-16 levels in all sensitive and resistant cell lines. The increments were 21.5% for UM-UC-2, 11.8% for UM-UC-9, and 31.0% for L1210 cells after 30 minutes incubation with 1 microM VP16. A slower efflux of VP16 was observed in verapamil treated cells in all three cell lines. There was a small increase in the nonexchangeable components in verapamil treated cells, although only 5-10% of VP16 was retained. No peak other than that of VP16 was detected in the HPLC chromatogram of extracts from both cell pellet and influx or efflux medium. PMID- 1754731 TI - Phase I evaluation of crisnatol (BWA770U mesylate) on a monthly extended infusion schedule. AB - Crisnatol is an arylmethylaminopropanediol derivative that has shown promise as an antitumor agent in preclinical testing. In a phase I trial using a monthly six hour infusion schedule the recommended dose for future phase II trials was found to be 388 mg/m2. Neurologic toxicity was dose-limiting in that trial and correlated with the attainment of a threshold plasma concentration of greater than 4.5 micrograms/ml. In this study we treated 15 patients with escalating doses of crisnatol from 450 mg/m2 to 900 mg/m2 administered at a rate of 50 mg/m2/hr over 9, 12, 15, and 18 hours. Toxicity was mild to moderate at all dose levels. However, serious central nervous system effects were noted in one patient at 900 mg/m2 over 18 hours whose plasma level was 6.5 micrograms/ml. This study has demonstrated higher total doses of crisnatol can be given if the drug is administered as a prolonged infusion in an attempt to avoid high plasma levels of the agent. PMID- 1754732 TI - Introduction: antimicrobial penetration into respiratory secretions. PMID- 1754733 TI - Fluoroquinolones in respiratory infections. AB - The fluoroquinolones have excellent activity against a number of respiratory pathogens, especially gram-negative bacteria, including beta-lactamase-producing Hemophilus influenzae and Moraxella catarrhalis. Several studies have shown ciprofloxacin to be effective in the treatment of acute exacerbations of chronic bronchitis, some community-acquired and nosocomial pneumonia, and acute exacerbations of bronchopulmonary infections in cystic fibrosis. The fluoroquinolones have less activity against Streptococcus pneumoniae and limited anaerobic activity, which should limit the use of these drugs in empiric therapy of community-acquired pneumonia where the pneumococcus or anaerobes play a predominant role. PMID- 1754734 TI - Aminoglycosides versus beta-lactams in gram-negative pneumonia. AB - Newer beta-lactam antibiotics with high levels of activity against gram-negative aerobic bacilli (including Pseudomonas aeruginosa) such as cefoperazone, ceftazidime, imipenem, and aztreonam may be suitable for monotherapy of gram negative pneumonia. Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin are also highly active against these same organisms and have been more extensively used, but are both ototoxic and nephrotoxic. Key therapeutic questions are whether beta-lactams can safely replace aminoglycosides for the treatment of gram-negative pneumonia, and whether monotherapy or aminoglycoside and beta-lactam combination antibiotic treatment is superior. There is remarkably little definitive clinical data in the literature to answer these questions, but available studies suggest that beta-lactam monotherapy may be adequate for Escherichia coli and Klebsiella pneumoniae pneumonias, but that combination therapy may be preferred for Pseudomonas aeruginosa, Serratia sp, Enterobacter sp, and Acinetobacter sp, largely based on rates of bacterial persistence and emergence of resistance. At this time, there are more data available to support aminoglycoside monotherapy than beta-lactam monotherapy in gram-negative pneumonia and remarkably little data to suggest superiority of two antibiotics over single agents when they have been compared prospectively. Thus, combination therapy remains a conservative recommendation until better studies are available. PMID- 1754735 TI - Antiviral agents in respiratory infections. AB - Viral respiratory illnesses are among the most common afflictions in the United States. Until recently, few agents were available to control these infections. Now, there are specific and nonspecific agents either to prevent or treat viral respiratory infections. For example, a better understanding of the pathogenesis of the common cold provided new insights into therapeutic intervention for that entity. In other instances (eg, influenza), the antiviral agent is so specific that there is a need for diagnostic information to guide therapy. Epidemiological clues, clinical symptoms, and some newer laboratory methods all contribute to the clinician's understanding of the cause of an individual respiratory illness and guide the choice of therapy. In other circumstances, information is being gradually developed that points toward the availability of a broad-spectrum antiviral drug with activity against at least five of the important respiratory viruses; its major limitation is that a cumbersome and expensive means of delivery to the patient is required. For such a drug to gain widespread use, a more practical method of delivery is necessary. PMID- 1754736 TI - Delivery of topical antibiotics: pharmacokinetics and clinical problems. AB - Despite major advances in new therapeutic agents to treat pneumonia, pneumonia remains a major cause of morbidity and mortality in hospitalized patients. Topical antibiotics offer many potential advantages in the treatment and prevention of nosocomial pneumonia. These include a high delivery of the drug to the site of infection and the potential for little systemic absorption and, as a result, reduced side effects. The potential disadvantages include failure of topical therapy to reach all diseased areas of the lung and the emergence of resistant organisms. Failure of many of the previous clinical studies has been ascribed to these potential disadvantages. However, little attention has been paid in previous clinical studies to actual dosage and regional distribution of aerosolized antibiotics in the lung and the pharmacokinetics of the aerosol after deposition. One major exception to this has been the use of aerosolized pentamidine, in which careful attention has been paid to nebulizer design, dosage to the lung, regional distribution, and pharmacokinetics. It should serve as the model for the testing of topical antibiotics therapy in the future. PMID- 1754737 TI - Antibiotic pharmacokinetic considerations in pulmonary infections. AB - The factors affecting the penetration of antibiotics into the respiratory tract and their clinical relevance in treating pulmonary infections are discussed in this article. The importance and interpretation of sputum, bronchial fluid, pleural fluid, and lung tissue levels are emphasized, including a tabular summary of published data on antibiotic levels in the respiratory tract. The relative predictive efficacy of antibiotics against pulmonary pathogens is best expressed by comparing tissue levels with the mean minimum inhibitory concentration of the infecting organism, ie, the "kill ratio." The kill ratio is the best way to compare dissimilar antibiotics in terms of their likely efficacy in treating pulmonary infections, ie, those with high kill ratios (greater than or equal to 2) are more likely to be associated with a favorable clinical outcome than those with lower kill ratios. The difficulties with interpreting pharmacokinetic data from various parts of the respiratory tract in terms of specimen timing, handling, processing, and interpretation are also discussed in this article. PMID- 1754738 TI - Cadmium causes increases of N-myc and multidrug-resistance gene mRNA in neuroblastoma cells. AB - Since cadmium exposure results in neuropathological alterations in central nervous system, we investigated the effects of cadmium on the gene expression of neuroblastoma (GOTO) cells. We observed an increase in mRNA levels of heat-shock protein (hsp) 70, hsp 90, hsp 32 and metallothionein after treatment of GOTO cells with cadmium, although the time courses of the changes of individual mRNA of the heat-shock proteins and metallothionein were somewhat different from each other. An accumulation of N-myc and multidrug-resistance gene (MDR1) mRNA was detected in the presence of cadmium. This is contrary to the previous report, in which an inverse correlation between the expression of MDR1 gene and N-myc oncogene in human neuroblastoma had been described. However, the increase of N myc and MDR1 mRNA in the present study is not likely due to the loss of regulatory mechanism of these genes by cytotoxic effects of cadmium, because active protective mechanisms such as heat-shock proteins and metallothionein could be induced under these conditions. PMID- 1754739 TI - [Chemosensitivity test by subrenal capsule assay (SRCA) in transitional cell carcinomas]. AB - From November, 1986 to October, 1989, the antitumor activities of several chemotherapeutic agents were tested by subrenal capsule assay (SRCA) in cases of 23 transitional cell carcinomas. Overall sensitivities of tested drugs to transitional cell carcinomas were compatible to clinical data and correlated with individual clinical courses. This method has some problems, but can be carried out at any institute and serve as an aid to the selection of chemotherapeutic agents. PMID- 1754740 TI - [A survey of the best bibliographic searching system in occupational medicine and discussion of its implementation]. AB - When occupational health personnel, especially occupational physicians search bibliographies, they usually have to search bibliographies by themselves. Also, if a library is not available because of the location of their work place, they might have to rely on online databases. Although there are many commercial databases in the world, people who seldom use them, will have problems with on line searching, such as user-computer interface, keywords, and so on. The present study surveyed the best bibliographic searching system in the field of occupational medicine by questionnaire through the use of DIALOG OnDisc MEDLINE as a commercial database. In order to ascertain the problems involved in determining the best bibliographic searching system, a prototype bibliographic searching system was constructed and then evaluated. Finally, solutions for the problems were discussed. These led to the following conclusions: to construct the best bibliographic searching system at the present time, 1) a concept of micro-to mainframe links (MML) is needed for the computer hardware network; 2) multi lingual font standards and an excellent common user-computer interface are needed for the computer software; 3) a short course and education of database management systems, and support of personal information processing for retrieved data are necessary for the practical use of the system. PMID- 1754741 TI - [MRI of normal pituitary glands and their surrounding structures]. AB - Normal MRI appearances of the pituitary glands and their surrounding structures were evaluated in 332 patients without sellar and parasellar diseases. The height of the pituitary gland was maximum at 10-19 years of age reflecting hormonal activity. The width of the pituitary gland decreased, while that of the cavernous sinus increased with aging. This is probably due to atherosclerotic change of the internal carotid artery. Females younger than 30 years of age tended to show a convex upper surface of the pituitary gland and the displacement of the pituitary stalk was common after 50 years of age. Almost all of the anterior lobe of the pituitary gland showed isointensity relative to the pons or cerebral cortex and the majority (85.1%) of the posterior lobe showed hyperintensity. However, the anterior lobe in 2 newborns showed hyperintensity similar to the normal posterior lobe in adults. The posterior lobe was located off the midline in 19.1% of the subjects. One case of pars intermedia cyst was discovered among 14 subjects who were administered Gd-DTPA. The dural membrane between the pituitary gland and cavernous sinus was recognizable only in 8.6% on the right side and 7.5% on the left side. Primary empty sella was identified in 4.5%. A knowledge of the above normal ranges and variations of the pituitary gland and its surrounding structures is important in diagnosing sellar and parasellar lesions. PMID- 1754742 TI - [Stress management of overseas Japanese in Kuwait]. AB - Forty percent of the Japanese businessmen in overseas positions are working in developing countries. However, few reports on the mental health care for them have been published. The Japan Overseas Medical Fund and The Kuwait Japanese Association has promoted the Kuwait Japanese Clinic. I had an opportunity to work at this clinic and to study the environmental health of Japanese businessmen in Kuwait. I found that in Kuwait, Japanese businessmen had to adapt to climatic, religious, cultural, and historical differences. Therefore, I investigated the incidence of stress related diseases which are caused by these environmental differences. Stress diseases occurred in 15.7 percent of total cases frequently, and some of them were very severe. After my stay in Kuwait, I believe that the setting up of medical information networks between various countries to alleviate medical anxiety and a system whereby instructions in the differences of medical systems in various countries would be very beneficial. PMID- 1754743 TI - In praise of audit. PMID- 1754744 TI - Social insurance medicine: a challenge to primary health care. PMID- 1754745 TI - Streptococcal throat infection: calculation of test standards and a comparison between an antigen detection test and culture. AB - The standard minimum sensitivity (94%) and minimum specificity (89%) of a group A streptococcus (GAS) test were calculated, assuming that no more than 10% false positive and no more than 2% false negative test results should be allowed. The clinical judgement of the need for immediate antibiotic treatment in tonsillitis/pharyngitis was an unreliable indicator of a GAS aetiology, 20-29% of the results being false positive and 2-10% false negative. The rapid antigen detection test Tandem Icon Strep A was not sensitive enough to be used as a single test, though it was specific enough. The sensitivity of culture almost reached the standard demand. Two combinations of rapid test and culture (sequence testing) were superior to the rapid test, but were not significantly better than culture. PMID- 1754746 TI - The costs of treating hypertension in Sweden. An empirical investigation in primary health care. AB - The treatment costs of hypertension in Sweden were calculated both at the individual and at the national level after an empirical investigation in primary health care. The average drug cost per patient and year was calculated as c. SEK 1220, the annual consultation cost as c. SEK 620, and the annual travel and time cost as c. SEK 230. About 500,000 people are treated pharmacologically for hypertension in Sweden, and about 25,000 non-pharmacologically. The total annual treatment cost for these patients was calculated as c. SEK 1100 million. The drug cost accounts for c. SEK 650 million, the consultation cost for c. SEK 330 million, and the travel and time cost for c. SEK 120 million. The drug reimbursement scheme pays almost half these costs, while the county councils and the patients pay approximately a quarter each. PMID- 1754747 TI - Telephone advisory service, visits to district nurses and home visits made by district nurses at a Swedish primary health care district. AB - All contacts with the district nurses were registered during a three-week period, daytime Monday to Friday, in a defined primary health care district (Vanersborg, Sweden): 855 incoming telephone calls, 1,016 visits to the district nurses (visits to child welfare unit excluded), and 380 home visits made by the district nurses. The telephone consultations comprised 38% of the total number of contacts and 14% of the time was devoted to this activity, visits to the district nurses at their reception units 45% of all contacts and 39% of the time, and home visits 17% and 47%, respectively. Symptoms from the upper respiratory tract and from the skin were the most common reasons for telephone consultations, while wounds and leg ulcers were the most common reasons for visits to the reception unit and for home visits. A great deal of the district nurse's work was requested by health centres and hospitals. PMID- 1754748 TI - Anaemia in elderly patients. Incidence and causes of low haemoglobin concentration in a city general practice. AB - Haemoglobin concentration was determined in all patients (530) over 70 years of age in a general practice in Oslo during an eight month period. 72 had anaemia and were investigated further. Iron deficiency was found in 13 patients and was most often caused by gastrointestinal blood loss. Chronic diseases, particularly chronic infections and rheumatoid arthritis, were responsible for anaemia in 34 patients. Renal failure caused anaemia in 14 patients. In 10 patients we found no explanation for the anaemia. Nine patients with a previously undiscovered disease were found, six of whom could be offered some kind of treatment. We conclude that anaemia in elderly patients in general practice is often caused by chronic diseases. The main cause of iron deficiency is blood loss, and routine prescription of iron is not justified in this age group. The therapeutic benefit from routine measurement of haemoglobin concentration is small and the test should be used selectively. PMID- 1754749 TI - Organization and problems in emergency dental care at Finnish health centres. AB - The Public Dental Service in Finland is, in principle, responsible for emergency dental services for the population. The organization of the prevailing emergency care system in the 215 health centres was studied. 90% of the health centres had some kind of emergency services, usually during regular working hours. Few health centres offered treatment outside normal hours or had a telephone-based back-up system. The main problems reported were the unpredictability of the need for emergency services, great variations in the number of patients, the heavy work load created by continuing treatment of emergencies, and shortage of personnel. PMID- 1754750 TI - Myocardial infarction risk factors in a semirural area in mid-Sweden. The population study "50-year-old people in Kungsor". AB - The mortality from ischaemic heart disease is higher in predominantly rural northern and western Sweden than in the more urban eastern and southern districts. This study was performed in a small semirural area in mid-Sweden with lower mortality from ischaemic heart disease in middle-aged men and higher mortality in middle-aged women than the national average. Smoking habits, serum cholesterol, and blood pressure were measured in all 50-year-old men and women in the community (n = 314) during a four-year period. In addition, the feasibility of using the local health care centre as a base for the study was tested. The health centre provided an excellent base for this population study. The non response rate was less than 3%, indicating that using local facilities and staff well known to the population might be an advantage. The risk factor levels seemed to be higher in Kungsor than in Uppsala, a community with low mortality from ischaemic heart diseases. The differences in risk factor levels could explain some, but not all of the differences in mortality from ischaemic heart diseases. Thus, other risk factors appear to be operating as well. PMID- 1754751 TI - Psychological symptoms and behavioural changes in Finns caused by fear of AIDS. AB - The purpose of the study was to explore personal fears about AIDS and their consequences in terms of psychological symptoms and behaviour. 1902 individuals, 15 to 64 years old, were selected at random from the Finnish population and interviewed by telephone (94%) or in person (6%). 2.5% regarded AIDS as a personal threat, while 12-13% exhibited psychological symptoms such as insomnia, depression, anxiety or episodes of fear. About 20% had taken measures to prevent HIV infection: 9% had increased their use of condoms, 6% had had themselves tested for HIV, and 5% had taken precautionary measures at work. The psychological status of individuals who feel at risk of AIDS should be assessed within the health care system because persistent feelings of danger may be a sign of incipient psychological decompensation. PMID- 1754752 TI - Body communication is a continuous process. The first encounter between patient and physiotherapist. AB - First encounters between patients and physiotherapists have been video-taped and analysed as part of a research project encompassing manual, psychomotor, and district physiotherapists. The main focus in this article is on body communication. The common features and differences between the patterns of communication established by the three categories of therapists are described and compared. Since human beings function and relate to each other as physical subjects, messages of interest and involvement will in some way be conveyed through their bodies. The recognition of this fact means that body communication is a central aspect of patient-centredness. The relationship, context, and actual basis of cooperation can only be understood by analysing the way in which professionals relate to their patients through their bodies. This is because body messages are conveyed continuously in any encounter between two people, while verbal communication is discontinuous. PMID- 1754753 TI - Treatment of bacterial vaginosis with metronidazole or pivampicillin. AB - In a double-blind randomized controlled trial from general practice, we assessed the efficacy of treatment with either metronidazole or pivampicillin in patients fulfilling the diagnostic criteria of bacterial vaginosis. 50 women were treated with metronidazole 500 mg twice daily and 54 with pivampicillin 700 mg twice daily, both for seven days. Evaluated four weeks after the start of treatment, we found a significantly higher cure rate in the metronidazole group (90%) than in the pivampicillin group (69%) (p = 0.01). Cure was defined as lack of fulfillment of the diagnostic criteria of bacterial vaginosis. Test for confounding according to parity and complaint of vaginal discharge showed no influence. Side-effects were significantly commoner in the pivampicillin group (28%) than in the metronidazole group (8%). We consider that metronidazole is a potent drug in the treatment of bacterial vaginosis, with pivampicillin as a useful alternative. PMID- 1754754 TI - Trauma in the elderly: the impact on the health care system. AB - The impact of injuries in the elderly on the acute health care system was assessed in terms of the cost of injuries. The cost of injuries in the elderly (greater than or equal to 60 years) was compared with that in the younger group (less than 60 years) in a health district in northern Sweden. Even though the elderly made up only one sixth of the total injured during a one year period, they accounted for 42% of the total cost of the medical care of injuries. The mean medical care cost increased significantly from the age of 60 years; the cost was four times higher in the older group than in the younger group. Severe injuries in the elderly cost almost 2.5 times more than those in the younger group. In conclusion, since the elderly place a heavy burden on the health care system, they urgently need to be given priority in injury research and injury intervention programmes. PMID- 1754755 TI - School injuries. Epidemiology and clinical features of 307 cases registered at hospital during one school year. AB - Injuries at school were studied for one school year in 57 primary and three secondary schools (13,733 students, aged 7-19 years) at Umea in northern Sweden. The injury rate was 22/1000 student years. There was a wide variation in injury rate between different schools. The boy/girl ratio was 1.1/1. Physical education was the dominating activity at the time of injury for the older students and play in the school yard for the younger. The majority of the students had a minor injury, but 17% had a fracture. The injured students did not seem to have more somatic, psychological or social problems than students in general. Fewer competitive sports and ball games and more adult supervision and organized activities during breaks are suggestions to reduce injuries at school. A hospital based injury registration system is well fitted for serving as a base for analysing school injuries. PMID- 1754756 TI - The occurrence of symptoms and the proportion treated in Swedish infants and their mothers. AB - Eighty-five per cent of 229 post-parturient women answered a questionnaire concerning the occurrence of symptoms in themselves and in their infants after discharge from two maternity wards up to the infant age of four months. Information about the treatment and drugs used was also requested. Although the level of maternal education differed between the two regions examined, the panorama of symptoms, the drug treatment, and the breastfeeding were reported mainly the same. Symptoms were common both in the mothers and in their infants. No symptoms were reported by six per cent of the mothers and for eight per cent of the infants. Many of the symptoms were not pharmacologically treated, but 70% of the mothers and 38% of the infants took one or more drugs besides vitamins. None of the drugs taken by the mothers was considered to have adverse effects on breastfeeding and none of the drugs given to the infants was considered to be ineligible. PMID- 1754757 TI - General practice characteristics and use of Pap-smear. PMID- 1754758 TI - Advances in lithotripsy. PMID- 1754759 TI - B&L technologies DP-1 lithotripter: the third generation. PMID- 1754760 TI - Direx Tripter X-1. PMID- 1754761 TI - Dornier MFL 5000 and compact lithotriptors. PMID- 1754762 TI - The MPL-9000. PMID- 1754763 TI - The Medstone STS: a technical review. AB - The Medstone STS does not require the urologist to compromise his lithotripsy success because of insufficient power, inadequate imaging, or restrictions caused by patient positioning. The attention to the details required for success in treatment in the investigators opinion make the Medstone STS a very attractive device for the performance of lithotripsy. PMID- 1754764 TI - The Northgate SD-3 dual-purpose lithotriptor. PMID- 1754765 TI - The Sonolith 3000. PMID- 1754766 TI - Extracorporeal shock wave lithotripsy with the Siemens Lithostar lithotriptor. PMID- 1754767 TI - Storz Modulith SL-20: the new optimal acoustic source for extracorporeal lithotripsy. PMID- 1754768 TI - Therasonics lithotripsy system. PMID- 1754769 TI - EDAP LT-01 piezoelectric lithotriptor. AB - This is a first-rate, well thought out lithotriptor. It is very user friendly. Although not as powerful as some of the earlier devices, it has the distinct advantage of not causing any tissue damage during treatment. The advantage is the ability to vary the delivery of the amount of power according to the needs of the situation. The learning curve for the operator is steep, and he/she very quickly becomes very proficient. Patience is needed with some stones to give enough shocks for total fragmentation, but that comes with experience. Balancing the ease of treatment against the occasional need for retreatment results in a definite bias for the patient being treated with this machine, and avoiding the reported problems attendant with spark gap equipment. This, in my opinion, is an excellent machine. PMID- 1754770 TI - Richard Wolf piezoelectric lithotripters: Piezolith 2300 and 2500. PMID- 1754771 TI - [Long-term venous access]. AB - The authors summarize the technique of placement of long term venous access systems. The complications encountered are described. As an example, the experience of the Institut Jules Bordet in this field is presented. PMID- 1754772 TI - [Performance of routine Doppler studies for screening of the fetus in de uterus in the 3d trimester of pregnancy]. AB - We did screening Doppler investigations of the foetus circulation during the third trimester of pregnancy, and established reference curves for Resistance and Pulsatility Indexes of the umbilical and middle cerebral as well as for the ratios of these indexes. We compared these indexes in groups of fetuses with different characteristics at birth. It turned out that low birth-weight, or the presence of dips in the fetal heart rate during labor is associated with some distinctive anomalies of the measured indexes compared with the control group with a normal birth-weight and no deceleration during labor. PMID- 1754773 TI - [Prevention of iatrogenic multiple pregnancies]. AB - A significant increase of twin and multiple pregnancies induced by infertility treatment has been observed. These high-risk pregnancies should be efficiently prevented. Gonadotrophin treatment for anovulation being the main culprit, it should be undertaken: 1) if other induction methods have failed. 2) under strict echographic and hormonal monitoring. After in vitro fertilization, number of embryos replaced should be selectively limited (to 2 or 3) on the basis of their vitality scores. Partial reduction of a multiple pregnancy should remain an exceptional solution. PMID- 1754774 TI - [Prevention of complications of ovarian stimulation in in-vitro fertilization]. AB - The ovarian hyperstimulation syndrome which is the most severe iatrogenic complication of ovulation induction, may range from mere abdominal discomfort to lethal thromboembolism. It is therefore, mandatory to be able to evaluate the risk of such complications. In in vitro fertilization treatment, maximal level and growth rate of oestradiol and also the number of oocytes retrieved, are significantly higher among patients who will develop an hyperstimulation syndrome than in a group of healthy controls. However, due to the large distribution of individual values, none of these variables can be predictive by itself. Only multiple discriminant analysis effected within the frame of a multicentric study might be able to define a specific and sensitive predictive function. PMID- 1754775 TI - [Chronic knee pain. Diagnosis: pigmented villonodular synovitis]. PMID- 1754776 TI - [Hormonal treatment of advanced cancer of the prostate]. PMID- 1754777 TI - [Example of team work between forensic medicine, odontology and entomology. Identification of human bones, dating of death and establishing the crime location]. PMID- 1754778 TI - [Allergic thrombocytopenia due to nitrofurantoin]. PMID- 1754779 TI - [Ex-situ hepatic resection]. PMID- 1754780 TI - [Introduction to the world of color in medicine]. PMID- 1754781 TI - [Poet-physicians in German literature]. AB - Starting with standards arising from the relationship between medicine and art in classical antiquity, biblical tradition and teutonic-pagan antiquity, this article roams through german literature from the Middle Ages up to the 20th century, from Hildegard of Bingen to Gottfried Benn and Alfred Doblin, guided by the question, how strongly medical knowledge and medical practise are reflected in the poetry of writing physicians. Individual dispositions and epoque-specific features are discussed. Special attention is given to Paul Fleming and Angelus Silesius, Albrecht von Haller and Friedrich Schiller, romanticism and Georg Buchner. PMID- 1754782 TI - [Hildegard von Bingen: physician--mystic--poet]. AB - Out of the multifaceted visionary writing of St. Hildegard from Bingen (1098 1179) three aspects are selected and commented on: 1. The cosmologically oriented art of healing showing man in its original state (constitutio) its actual condition (destitutio) and the expected healthy final state (restitutio); 2. An universal vision oriented on mystic enligthment proposing the individual as creation (opus Dei), as partner (opus alterum per alterium) and as worker on nature (opus cum creatura); 3. The esthetic dimension of universal and human perception as expressed by Hildegards songs (carmina) which culminate in hymns on the "celestrial Jerusalem". We should consider, that these aspects--beyond their historic roots--indicate ways for healing and salvation of the integral individual. PMID- 1754783 TI - [Midlife crisis: crisis in the middle of life]. AB - Since ancient times man tried to understand the roots of his obviously often irrational behaviour. According to the prevailing "Zeitgeist", hypotheses for it ranged from demonical possession, psychological schools of thought to the role of transmitter substances at the synaptic level. For ages it has been observed and described, that men goes in his development through typical and predictable phases with their typical crises. Poets knew and wrote about it since the dawn of culture but science got interested in it only in this century. Elliot coined the term "midlife crisis" in 1965, turning attention to an age-group which was before practically ignored by psychology. He pointed out that due to a collision between developmental factors and a static identity a crisis occurred in human beings, characterized by a feeling of despair, goallessness, fatigue and consciousness of significant basic anxiety. In response to such pressures a change of comportment takes place which puzzles the people closest to the stricken. Established patterns of behaviour seem to dissipate in favour of unusual, unexpected, adolescent or even crazy actions. Many examples from history, ranging from Dante to Gauguin seem to prove the point. Realizing the presence of the crisis and its origin and interpreting it as a call for change, reorientation and new definition of priorities present a great chance to adjust one's life at this important turn. It is of great importance to recognize, that changes must take place in one's inner values and that trying to escape into frenzied activities leads nowhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754784 TI - [Paracelsus at the horizon of medicine]. AB - After a brief review of the life and work of Paracelsus (1493-1541) the five spheres of existence of the healthy as well as the sick individual are characterized (theory of the 5 entities). Founding on this theoretical orientation of existence Paracelsus constructs his "house of medicine" which is resting on 4 pillars: on "Philosophia" as natural and human science, on "Astronomia" as structured chronologic order, on "Alchimia" as science of the preparation of materials and on "Physica" providing the ethical prerequisite for medical practise. Paracelsus believes the physician to represent an educated expert applying standards to the other faculties as well; in his eyes medicine represents the "cornerstone of university". PMID- 1754785 TI - [Medical ethos of Paracelsus]. AB - 450 years ago the Renaissance doctor Theophrastus von Hohenheim called Paracelsus (1493-1541) died. Inspite of a famous name and his renowned challenging nature, his way of thinking and his work remain in many parts unknown. His professional ethics revolve around mercy, charity and his passion for medical art. In his book 'Paragranum' he waves the ethics as a virtue into his succint concept of a 'new topical and veritable medical science'. It is the aim to show the Paracelsian professional ethics in its timeless fundamentals, as in its very personal character. PMID- 1754786 TI - Perioperative antibiotic prophylaxis of wound and foreign body infections: microbial factors affecting efficacy. AB - Numerous microbial factors are responsible for perioperative infections and influence the efficacy of antibiotic prophylaxis. These factors include the staphylococcal carrier state, bacterial adherence to a number of host proteins, the production of glycocalyx by sessile bacteria, and shifts in antibiotic resistance. A full understanding of the mechanisms involved will lead to further reductions in the number of postoperative infections. Unfortunately, the microbial factors affecting prophylaxis cannot be evaluated separately under clinical conditions; they are easier to study under circumstances whose bacteriologic features are well defined and in which the presence of foreign materials (e.g., sutures) greatly potentiates pathogenic mechanisms. Such circumstances exist, for example, in infections developing after "clean" surgery and in experimental models. Since even clean wounds are found to be contaminated when sampled carefully, the control of infection is more a quantitative than a qualitative problem. The critical period for the development of infection is short: an antibiotic course not exceeding 24 hours seems effective in preventing infection. PMID- 1754787 TI - Role of antimicrobial pharmacokinetics and pharmacodynamics in surgical prophylaxis. AB - The pharmacokinetic and pharmacodynamic properties of antimicrobial agents used for surgical prophylaxis are reviewed. Since levels in tissue homogenates depend on the amount of drug present intracellularly, they do not accurately describe the relation between concentrations in serum and those in interstitial fluid. Levels of free drug in serum are good predictors of the time course of concentrations of unbound drug in interstitial fluid. An increase in protein binding does not reduce the area under the curve (AUC) of free drug for beta lactam agents eliminated predominantly by glomerular filtration. Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period for which the free-drug concentration exceeds the minimal inhibitory concentration (MIC) is an important parameter in the efficacy of beta-lactam antibiotics. In contrast, the AUC is the major parameter in the efficacy of aminoglycosides and quinolones. Although studies with animals support the above concepts, data for humans are limited. Until additional clinical trials dictate other conclusions, the goal of prophylaxis with beta-lactam agents should be to provide serum levels of free drug above the MIC for common contaminating bacteria for the entire surgical period. PMID- 1754788 TI - Role of the environment of the operating suite in surgical wound infection. AB - Most surgical wound infections are acquired in the operating room from the patient's own microbial flora. The remainder are acquired mainly from the staff in the operating room during surgery. The inanimate environment (e.g., walls, floors, and surgical instruments) has little relevance to the spread of infection. Because the air is an important route of spread in joint prosthesis operations, the routine use of an ultraclean air system and exhaust-ventilated clothing is frequently recommended. The value of such a system in other types of clean surgery is doubtful, but other measures, such as the following, may provide similar results at less cost: reduction of the number of persons in the operating room; a policy of not opening doors during operations; the use of comfortable, washable, bacteria-impermeable clothing by the operating-room staff; and concentration of the airflow over the operation site rather than over the whole operating room. PMID- 1754789 TI - Alteration of cutaneous staphylococcal flora as a consequence of antimicrobial prophylaxis. AB - Antimicrobial agents given as prophylaxis have profound effects on the microbial flora of the skin. Coagulase-negative staphylococci cultured from the skin of patients after cardiac surgery have been found to be more resistant to antimicrobial drugs than organisms cultured from the same skin sites preoperatively. Evidence exists both for the selection of resistant organisms from the preoperative flora and for the postoperative acquisition of such organisms from the nosocomial environment. Staphylococci causing postoperative infections have the same antimicrobial resistance phenotypes as do colonizing isolates; this observation suggests that colonized patients and hospital staff make up a nosocomial reservoir for resistant organisms. PMID- 1754790 TI - Methodologic aspects of clinical studies of perioperative antibiotic prophylaxis. AB - Many issues affect the design, conduct, and analysis of clinical evaluations of perioperative antibiotic prophylaxis. The most important of these are the selection of appropriate procedures for evaluation, the choice of meaningful outcomes, the comparison of outcomes among groups of patients who are really comparable to one another, the unbiased assessment of outcomes, the assessment of a number of patients sufficient to provide adequate statistical power for the detection of meaningful differences, and the generalizing of results. In evaluating perioperative prophylaxis, investigators often strive to identify small absolute differences among the risks of infections with different prophylactic regimens. For many specific procedures and drug regimens, such evaluations are limited by the difficulty of studying a sufficient number of individuals. Although randomized clinical trials are the standard for clinical evaluation, observational data may also prove useful under some circumstances. PMID- 1754791 TI - Antimicrobial prophylaxis for appendectomy and colorectal surgery. AB - Current opinion favors the use of antimicrobial prophylaxis in all operations for acute appendicitis. In clinical trials with placebo controls, the reduction in the rate of postoperative infectious complications is most apparent in perforated and/or gangrenous appendicitis, but benefits are also seen in nonperforated appendicitis and even in those with a normal appendix. In elective colorectal operations, it has been established that all patients should receive prophylactic antibiotics. The choices are an oral bowel preparation consisting of neomycin or kanamycin combined with erythromycin or metronidazole; a parenteral antimicrobial drug such as cefoxitin or cefotetan; or a combined oral/parenteral regimen. Risk factors for postoperative wound infection include a prolonged duration of surgery (greater than 3.5 hours) and rectal resection. The most popular prophylactic regimen employed by American surgeons, particularly in the presence of adverse risk factors, is oral neomycin/erythromycin along with a short course (one to three doses) of a systemic cephalosporin active against anaerobes. PMID- 1754792 TI - Prophylactic antibiotics in gynecologic and obstetric surgery. AB - Preventing infections at operative sites has long been a goal of gynecologic and obstetric surgeons. These infections constitute the leading cause of morbidity after both elective and emergent surgical procedures. Serious sequelae such as bacteremia, septic shock, phlegmon, pelvic abscess, septic pelvic thrombophlebitis, wound abscess, and fascial dehiscence may complicate primary infections, with devastating results. Early attempts to prevent postoperative infections concentrated on aseptic techniques and the modification of surgical skills. Soon after the introduction of antibiotics into clinical medicine, surgeons began to administer these drugs to clinically uninfected women to prevent operative-site infection; that practice has been documented and assessed in a large volume of literature. This article reviews the chronologic development of prospective data in the areas of benign gynecology, obstetrics, gynecologic oncology, and infertility and makes recommendations regarding antibiotic prophylaxis of infections associated with surgical procedures. PMID- 1754793 TI - Antibiotic prophylaxis in orthopedic surgery. AB - This review covers four areas: the use of prophylactic antibiotics in orthopedic surgery not involving prosthetic devices; the use of prophylactic antibiotics in prosthetic joint implantation; the use of antibiotic-containing cement in prosthetic joint surgery; and the use of prophylactic antibiotics for dental procedures in individuals with implanted prosthetic joints. The major conclusions are as follows: (1) Prophylactic antimicrobial agents lower the rate of wound infection following surgery for closed hip fractures. (2) Antimicrobial prophylaxis reduces the frequency of deep wound infection following total joint replacement; operating rooms with ultraclean air have a similar effect. (3) Antibiotic-impregnated cement is as effective as systemic antibiotics in preventing early infection following total joint replacement. (4) For routine dental work in most patients with total joint replacement, there is insufficient evidence to support antibiotic prophylaxis; for such individuals with periodontal disease or potential dental infection, antimicrobial prophylaxis seems indicated. PMID- 1754794 TI - Antibiotic prophylaxis in trauma: penetrating abdominal injuries and open fractures. AB - Infection is an important cause of late morbidity and mortality following traumatic injury. As part of a coordinated treatment effort for the injured patient, preventive antibiotic use can reduce subsequent infectious complications. Available evidence supports the use of antibiotic(s) with activity against both aerobic and anaerobic enteric pathogens for patients with penetrating abdominal injuries and bowel penetration. Patients with open fractures benefit from the use of an antibiotic with activity against Staphylococcus aureus. Data on the ideal dose and duration of antibiotic administration in these situations are incomplete. It is likely that the best results will be obtained with early parenteral administration of large doses of the chosen antibiotic continuing for less than or equal to 24 hours. For injuries other than penetrating abdominal wounds and open fractures, definitive information is not available. PMID- 1754795 TI - Prophylaxis in otolaryngologic surgery and neurosurgery: a critical review. AB - In an assessment of prospective, controlled studies of antimicrobial prophylaxis against infections following otolaryngologic surgery and neurosurgery, the English-language literature on this topic was reviewed. Rates of infection following clean otolaryngologic operations are the same for patients receiving prophylaxis and those receiving placebo. For patients with head and neck cancer, rates of postoperative infection without antibiotic prophylaxis in clean surgery are less than 1%, and prophylaxis is not indicated; in contrast, in clean contaminated procedures (infection rate, 18%-87%), prophylaxis is highly protective, although several studies have shown no advantage to its prolongation beyond 24 hours. For the latter operations, drugs with adequate activity against oral anaerobes are essential, whereas the need for coverage against Enterobacteriaceae is doubtful. In clean and clean-contaminated neurosurgical procedures, the rate of protective efficacy of prophylaxis ranges between 63% and 76%. For shunt operations the available evidence favors prophylaxis, but the wide range of infections reported mandates a large-scale multicenter trial to decide the issue. PMID- 1754796 TI - Antibiotic prophylaxis in clean surgery: peripheral vascular surgery, noncardiovascular thoracic surgery, herniorrhaphy, and mastectomy. AB - Studies published in the English-language literature on the use of prophylactic systemic antibiotics in vascular surgery, noncardiovascular thoracic surgery, mastectomy, and herniorrhaphy were reviewed. The effectiveness of antibiotic prophylaxis in preventing deep and superficial wound infections in peripheral vascular surgery appears to be well documented, especially if prophylaxis is directed against Staphylococcus aureus. In clean thoracic surgery the evidence is equivocal, and no studies have sufficient statistical power to eliminate the possibility even of a 50% reduction in incidence. In herniorrhaphy and mastectomy some evidence from a much more powerful study suggests that antibiotic prophylaxis may result in a decrease of up to 50% in wound infections, but whether these data can be generalized uncritically to all clean wounds is still a matter of debate. Accordingly, only guarded recommendations can be made regarding the use of prophylactic antibiotics in procedures associated with a very low risk of serious infection. PMID- 1754797 TI - Perioperative antimicrobial prophylaxis in middle Tennessee, 1989-1990. AB - The patterns of use of perioperative antimicrobial prophylaxis were assessed in a randomly selected sample of short-stay hospitals in middle Tennessee. Overall, 438 procedures (48%) were associated with antimicrobial prophylaxis. Prophylaxis was more common in hospitals with more than 400 beds than in smaller hospitals. Moreover, prophylactic antibiotics were given more often for procedures with a proven indication for prophylaxis than for those without a proven indication (60% vs. 41%, P less than .05); this relationship remained constant regardless of hospital size (common odds ratio, 2.09). However, prophylaxis for procedures with a proven indication was more likely to be given in teaching hospitals than in nonteaching hospitals (odds ratios, 5.41 vs. 1.94). The duration of prophylaxis was less than 2 days for 89% of procedures. A wide variety of agents were used. This study suggests that while improvements have been made over the past decade in decisions about the duration of prophylaxis, considerable variation remains in the selection of the procedures in which such treatment is administered and of the antimicrobial agents used. PMID- 1754798 TI - Cost and benefit of perioperative antimicrobial prophylaxis: methods for economic analysis. AB - Cost-benefit analysis of perioperative prophylaxis with antimicrobial agents involves efforts in two main areas: first, economic aspects of a decision whether or not to use prophylaxis are examined; and second, the financial benefit of a drug or regimen is compared with that of the currently used drug or regimen. Both cost and benefit have a number of components, both direct and indirect; methods are available for the analysis of some of these components. Systematic economic analysis permits evaluation of the relative importance and magnitude of the various elements of cost and benefit. Often the analysis shows that information about one or more elements is not worth collecting because it will have minor or no impact. Failure to clearly identify the viewpoints of persons interpreting the data hinders analysis; systematic economic analysis makes these differences in viewpoint clearer. Convincing economic data in favor of prophylaxis exist for some operative procedures; hospitals should insist that these regimens be implemented. Surgical wound infection is the only type of nosocomial infection for which a consistent drop in rate of occurrence has been seen during the past decade. This drop undoubtedly is related in part to the perioperative use of antimicrobial agents. Perhaps these results constitute the best cost-benefit assessment of all. PMID- 1754799 TI - The path to new FDA guidelines for clinical evaluation of anti-infective drugs. AB - This article describes the current collaborative effort of the U.S. Food and Drug Administration and the Infectious Diseases Society of America to generate new general and disease/organism-specific guidelines for the evaluation of anti infective agents. The description includes examples of proposed changes from draft documents. If approved and implemented, the envisioned changes should enable investigators and sponsors to improve the quality of clinical trials of anti-infective drugs. The ultimate goal is to provide physicians with the best information about new drugs and thus to enhance the care of patients with infectious diseases. PMID- 1754800 TI - Biochemical events controlling initiation and propagation of the S phase of the cell cycle. PMID- 1754801 TI - Synergism in the control of force and movement of the forearm. PMID- 1754802 TI - [Results of assays of estrogen, progesterone and androgen receptors in stage I and II adenocarcinoma of the endometrium]. AB - The prognosis for adenocarcinoma of the endometrium is dependent on the findings of the histopathological assessment of the tumor. In a retrospective study of patients treated in initially by surgery, the estrogen and progesterone receptors were assayed 89 times and the androgen receptors 64 times. No statistically significant correlation was found between any of these receptors and the degree of structural differentiation or degree of infiltration of the myometrium. The absence of any one of these receptors had no negative impact on the overall survival nor on recurrence-free survival. The same was true for the 9 tumors which were devoid of both estrogen and progesterone receptors. In the authors' experience, the results of these hormone assays did not provide any further information on which to base the prognosis of endometrial cancers. PMID- 1754803 TI - [Indications for bilateral ligation of the uterine arteries and the hypogastric arteries in refractory obstetrical hemorrhages]. AB - The author describes the various indications for obstetric hemostatic vascular ligations accepted today by specialists. In serious post-partum uterine hemorrhage due to pathology of contraction and or retraction of the uterus, hemorrhage refractory to classical conservative treatment, specialists use either bilateral ligation of the uterine arteries at the site of their ascending branches, or bilateral ligation of the anterior branch of the internal iliac artery (BLILA), sometimes thus avoiding hemostatic hysterectomy. However hemostatic vascular ligations may be attempted only rarely, in particular when hemostasis procedures follow one after the other in the absence of an immediate threat to the mother's life. Prophylactic BLILA may be performed immediately after hemostatic hysterectomy (as a complement before closing the abdominal wall). It thus guarantees hemostasis and avoids the possibility of reoperation to achieve hemostasis, which could be fatal. BLILA performed at the postoperative (posthysterectomy) stage, during hemostatic reoperation, is of a curative nature and is effective only when hemorrhage is coming from a branch of the internal iliac artery. In severe post-partum hemorrhage coming from the peri-uterine regions supplied by the internal iliac arteries, only BLILA may be useful when local surgical hemostasis is ineffective or impossible. PMID- 1754804 TI - [Therapeutic termination of pregnancy. Diagnosis and protocols. 54 cases]. AB - The authors present 54 cases histories of therapeutic terminations of pregnancy. The mean age of the patients was 28.6 years at the time of diagnosis with the following in indications for the antenatal diagnosis in order of decreasing frequency: clinical history, age of the mother, seropositive for toxoplasmosis or rubella, a high fetal alpha protein level and ultrasound signs. They highlight the usefulness of ultrasound in reaching a decision as to whether pregnancy should be terminated (as it was in 25 cases out of 49) and the predominance of diagnoses of karyotype abnormalities. They also compare the various prostaglandin s used in this study (analogs of PGE1 and PGE2, diniprost). Their results, in accordance with the literature were good for gemeprost and sulprostone with expulsion in 29 out of 32 cases within 24 hours and in 9 cases out of 11 within 20 hours respectively. PMID- 1754805 TI - [Eclampsia at the Hospital Center of Libreville. 53 cases among 41,285 deliveries from 1985 to 1989]. AB - Eclampsia is a serious complication at the end of pregnancy. This retrospective study over a 5-year period at the Libreville CHU hospital shows that the incidence of 0.12 p. cent is comparable to the incidence fond in other countries at a similar level of development. Promoting causes include youth of the patients, twin births, the "cold" season, the lack of follow-up after prenatal consultations. The consequences are increased maternal and perinatal death. Cesarean section remains the best way of dealing with an attack of eclampsia and improves both maternal and fetal prognosis. It is possible to eliminate, or at least reduce, the number of cases by developing conscientious and regular prenatal consultations. PMID- 1754806 TI - [Profile of referred pregnancies from the Tunisian Sahel]. AB - Investigation of the referral system for pregnancies from peripheral maternity units to the Maternity clinical of the main teaching hospital (CHU) in the region of Monastir has shown that one in five pregnancies is referred. The referred pregnancies account for 30 percent of the obstetrical activity of the CHU and reveal a high risk sociodemographic profile. The outcome of pregnancy is generally less good than that of non-referred cases. Evaluation of the referral system has shown that some of the cases did not require referral. The effectiveness of this system can be improved by used a grid to refer high-risk pregnancies. PMID- 1754807 TI - [Late abdominal pregnancy. A case report]. AB - A case of 29 weeks gestation abdominal pregnancy is reported as an illustration to a study of that rare gestation mostly occurring in developing countries. Most abdominal pregnancies are secondary. The most common clinical signs are the abdominal pain and uncomfort. The physical signs arise the suspicion of abdominal pregnancy which is confirmed by ultrasound. Most authors don't delay the surgical procedure after the diagnosis. The placenta is mostly often left in situ and mostly. No methotrexate is administered to improve the placenta involution. The abdominal pregnancy is of very bad fetal prognosis and very at risk for the pregnant woman. PMID- 1754808 TI - [Benckiser hemorrhage with a living fetus]. PMID- 1754809 TI - [Computer-assisted model of weight gain during pregnancy]. AB - The goal of this study was to modelize the evolution of "ideal" weight gain during pregnancy and to generate automatically the appropriate diet. This computerized model has been developed on a microcomputer and has two units: the first unit calculates the "ideal" weight gain during pregnancy, based on the curves of Rosso which show that weight gain is not linear with term and depends of the prepregnancy weight. The second unit calculates the appropriate diet which is depending for the first visit on height, prepregnancy weight and weight gain and for the followed visits on weight gain and the diet situation of the previous visit. The next step will be the medical evaluation of this computer-aided modelization of weight gain during pregnancy. PMID- 1754811 TI - Antinuclear antibodies to RNA-binding proteins in SLE. AB - The presence of autoantibodies is a prominent feature of connective tissue disease (CTD). At first glance there is a wide range of antibody specificities, but in the individual patient the autoantibody profile is much more restricted. Thus, certain antinuclear antibodies are not only strongly associated with disease expression, but also identify distinctive serological subsets within the spectrum of CTD. In turn, these subsets are associated with particular patterns of disease expression. With increasing knowledge of the molecular nature of the autoantigen targets, the relationship between fine specificity of the antibody response and disease manifestations is being further defined. PMID- 1754810 TI - Anti-dsDNA: choice of assay in relation to clinical value. AB - Antibodies to DNA are quite specific for systemic lupus erythematosus (SLE) and occur in the majority of SLE patients. Therefore, their detection is an important diagnostic aid to the clinician. Detection of anti-dsDNA may precede the diagnosis of SLE by more than a year. Fluctuations in the level of anti-dsDNA in an individual patient may give important information on the clinical status of the patient. Four of the most important methods developed for the measurement of anti-dsDNA antibodies will be discussed in this paper: the Farr assay, the PEG assay, the indirect immunofluorescence test on Crithidia luciliae and the ELISA. They will also be compared with one commercially available (Farr) assay, the Amersham anti-dsDNA kit. Each method, detects a part of the spectrum of anti dsDNA antibodies produced by a patient. The Farr assay is the most specific for SLE; however, milder forms of the disease in which patients have only low avidity anti-dsDNA may easily be missed by this technique. Clinically, high avidity anti dsDNA is related more frequently to the occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are found more often in patients with central nervous system involvement. Traditionally, SLE is considered an immune-complex disease, in which inflammatory processes are initiated by local deposition of DNA/anti-dsDNA complexes. More recently, a major role was thought to be played by crossreactions of anti-dsDNA with tissue constituents. Our current view, however, is that such a crossreactivity plays only a minor role; we postulate that binding to glomerular constituents is caused by anti-dsDNA antibodies complexed with DNA and histones. PMID- 1754812 TI - Kidney disease in systemic lupus erythematosus. AB - Glomerulonephritis is a major determinant of outcome in patients with systemic lupus erythematosus. Persistently active lupus nephritis imposes serious threats of end-stage renal failure and cardiovascular morbidity. Sustained corticosteroid treatment has been characterized as having an uncertain net benefit on the control of lupus nephritis, mainly because these drugs have relatively weak efficacy and they have been shown to confer their own set of cardiovascular risk factors. Controlled trials of corticosteroids, azathioprine and cyclophosphamide have demonstrated that the best control of clinical activity of proliferative lupus nephritis is attained with cyclophosphamide. To date, intermittent pulse cyclophosphamide treatment has produced the most favorable balance of efficacy and toxicity in patients with lupus nephritis. PMID- 1754813 TI - The central nervous system in systemic lupus erythematosus. AB - Management of central nervous system (CNS) involvement is one of the most challenging problems in systemic lupus erythematosus. This article reviews the spectrum of CNS manifestations present in this disease, their diagnosis and pathogenesis, as well as an approach to their treatment and prognostic implications. PMID- 1754814 TI - Systemic lupus erythematosus and pregnancy. AB - This article critically analyses the data in the literature on pregnancy in women with systemic lupus erythematosus. Based on the results of recent controlled prospective studies, it is apparent that the long-standing opinion that pregnancy induces exacerbation of the disease should be revised. The presence of active disease and/or a significant loss of renal function at conception are not only associated with a high risk of maternal complications, but also with high frequencies of loss of the fetus, as well as pre- and dysmaturity. Recently, the presence of antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies, has been recognized as being important for the occurrence of death of the fetus, in particular, late in the pregnancy. This is probably due to thrombosis occurring in the placental vessels. However, the results of randomized studies on treatment with antithrombotic drugs and/or procedures lowering, antibody levels must be available before we will know whether the presence of these antibodies should be coupled to specific instructions or not. Although there is a strong association between the neonatal lupus syndrome and the presence of anti-SSA antibodies in maternal blood, the finding of anti-SSA antibodies has up to now had no therapeutic implications. It is concluded that pregnancy in SLE deserves extensive preconceptional counseling and close cooperation between the internist, rheumatologist, obstetrician and the neonatologist. PMID- 1754815 TI - Prognostic factors in systemic lupus erythematosus. AB - In the past 40 years an impressive improvement in the prognosis of SLE patients has occurred. Factors which might be responsible for this improvement are discussed. Two of the factors most frequently cited are the advances in disease recognition and treatment. However, as already noted by Albert (1979) this is questionable, as average disease duration and survival have increased in a linear fashion related to the number of publications devoted to this subject from 1950 on. Further evaluation of the literature shows that the most prominent factors which have an impact on the survival rate are specific disease manifestations (lupus nephritis) and the overall disease course (number of exacerbations). This effect of morbidity on the survival rate is greater than that of factors such as sex and race. Socio-economic factors or age at onset have no effect on the outcome. PMID- 1754816 TI - Quantitative clinical assessment of disease activity in systemic lupus erythematosus: progress report and research agenda. AB - No single test allows an adequate measure of disease activity in multisystem diseases such as systemic lupus erythematosus (SLE). In order to evaluate the spectrum of manifestations of disease activity in SLE, investigators have developed numerous ad hoc scales which have not been tested for their validity or reliability. Three instruments have been extensively studied: the British Isles Lupus Activity Group instrument (BILAG), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus Activity Measure (SLAM). All three have been demonstrated to have convergent and construct validity when compared to the clinician's judgement. The summation of the number of criteria of the American Rheumatism Association (ARA) SLE criteria has been shown to be an inadequate measure of disease activity. Standardized measures of disease activity for SLE should enhance our ability to compare results from different centers in finer distinctions than dead or alive. PMID- 1754817 TI - Treatment of systemic lupus erythematosus: which options do we have for therapy regimens? AB - The prognosis of systemic lupus erythematosus has improved markedly. This has been due to various factors: improved serological testing leading to better diagnosis, better understanding of secondary complications, and the possibility of treating these. How much has improved treatment of the primary disease process contributed to the improvement in prognosis? We have evaluated the clinical outcome of 56 patients with lupus nephritis proven by biopsy, followed at out hospital over the past 16 years. During this period various therapies were used during active periods of the disease, based on literature data or participation in trials. Prognostic risk factors for the development of end stage renal disease (ESRD) appeared to be: WHO-class IV histopathology of the renal biopsies, male sex and raised serum creatinine. Development of ESRD at 5 years was 13% and at 10 years was 30%. Overall survival was 95%. Based on data from well controlled trials performed at the National Institute of Health (US) and our observations the need for well conducted long-term prospective randomized trials is stressed again. PMID- 1754818 TI - Pathogenic anti-DNA idiotype (16/6 Id) in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is regarded as a classical autoimmune disease. Despite this belief, no one has been able to induce the disease in naive animals, neither with DNA nor with anti-DNA antibodies. We report on the induction of SLE in BALB/c mice following immunization with a pathogenic anti-DNA idiotype (16/6 Id) or its anti-Id. We also report on a specific treatment with T suppressor cells specific for the 16/6 Id. The induction of SLE in naive mice with a pathogenic anti-DNA Id suggests an additional mechanism for the diversity of manifestations in this disease. PMID- 1754820 TI - [Uniform requirements for manuscripts sent to medical journals]. PMID- 1754821 TI - [Rhino-bronchial syndrome: new diagnostic approach]. AB - The studies in relation to rhino-bronchial syndrome are very few. That's true because of the diagnosis and treatment of the specimens is not made in a randomized way. And because of the many different etiology. In this paper two hundred and thirty files were studied within the diagnosis of RBS among patients consulting in the Pediatric Allergy Service in 1989. The results show that this process is multifactorial: allergic 72%, infections 23% and functional (gastric reflux) in 4%. There was improvement with specific treatment with immunotherapy and general measurements in 82%. Since fourth month of treatment. PMID- 1754819 TI - Pathogenesis of SLE: immunopathology in man. AB - Antibodies against native DNA are not only a disease-specific marker for systemic lupus erythematosus (SLE); in addition, there is good direct evidence that these antibodies also play a major part in pathogenic mechanisms leading to systemic and organ-specific disease manifestations. The origin of anti-dsDNA antibodies is still poorly understood, especially as dsDNA per se is not immunogenic. As recently shown, evidence is now accumulating that anti-dsDNA antibodies are not germline-encoded but antigen-driven, as demonstrated by the establishment of human anti-dsDNA antibody clones from SLE patients and sequence analysis. In sera of SLE patients there is an elevated level of nucleic acids, which indicates that defective clearance mechanisms for nucleic acids are present. The question as to whether these nucleic acids could serve as an antigen has been recently addressed by studies of plasma nucleic acids isolated from circulating immune complexes from SLE patients. These studies indicate that plasma nucleic acids in SLE patients have structures of amino acid sequences which have a striking homology with the gag-pol overlap region of HIV-1. Whether these nucleic acids play a role in the pathogenesis of SLE, indicating the involvement of a retrovirus in the pathogenesis, or whether they rather reflect an amino acid homology with an endogenous human retrovirus family is not yet known. PMID- 1754822 TI - [Correlation of the degree of bronchial hyperreactivity and the intensity and onset of symptoms in asthmatic children]. AB - We studied 51 children with stable bronchial asthma, we did a challenge with methacholine in different dilution until we found their PD20. Once we have it, we correlate this results with the age of onset of asthma and the severity of the symptoms. The results shows that if the symptoms start early in the life had more severe asthma and the PD20 is lower, this means that they have more hyperreactivity. Our results are similar to those found in the literature. PMID- 1754823 TI - [Characterization of the desmoglein in renal cells in culture]. AB - Desmosome junctions are found in epithelial tissues. They both link cells externally and anchor cytoplasmic intermediate filaments to the plasma membrane. Quantitative and qualitative abnormalities in intercellular junctions have been described in a broad spectrum of human and animal cancers. Current efforts are aimed at exploring the possibility that some of these defects may account for the hallmarks of malignancy, namely tumour invasion and metastasis. Desmosomes are constituted by several proteins, one of them is desmoglein-1 (DG-1), a transmembrane glycoprotein who glycosylated portion is major component of the adhesion mediating desmoglia. In order to know the similarity between tissue DG-1 and cultured renal cells DG-1 was used antisera raised against DG-1 to identify cross-reacting components. Anti DG-1 antibodies stained cell-cell boundaries in a punctate fashion in epithelial tissue and on densely grown monolayers of renal cells. Radioimmunoprecipitation and immunoelectrotransference show positive reaction with anti DG-1 antibodies with desmosomes obtained from epithelial tissue and renal cells monolayers, but last one was less positive. Results suggest some minor differences between DG-1 extracted from diverse sources but they have a commun immunodominant epitope. PMID- 1754824 TI - [Influence of occupational lead exposure on the concentration of immunoglobins and immune cellular functions in humans]. AB - The evaluation of immunological conditions of 14 workers occupationally exposed to lead, and the comparison of these results with those of a non-exposed control group, with similar age and sex, were the aims of this study. It was determined the mean values of lead in blood. In exposed workers it was 46.9 micrograms/dl; while in the control group it was 10.9 micrograms/dl. Levels of immunoglobulin decreasing while increasing lead concentration in blood were found in those exposed. It was also found a significant lessening in the formation of rosette in relation to the control group. PMID- 1754825 TI - [Changes in the configuration of synapses in the cerebral cortex in laboratory rats after termination of epileptic seizures during kindling]. AB - The sensorimotor area of the cerebral cortex of the laboratory rat was repeatedly stimulated by electric current after 10-minute intervals which led to the development a gradual prolongation of self-sustained after-discharges (SSAD). One and 10 minutes after termination of the third SSAD the authors analyzed under the electron microscope synapses type I after to Gray from the second cortical homotopic area of the unstimulated hemisphere. They evaluated the curvature of the active zone of synapses. Evidence was provided that one minute after termination of the fit the number of negatively curved synapses increased and the number of synapses with a straight active zone decreased. The number of synapses with a positively curved active zone does not change. Ten minutes after termination of SSAD in the experimental animals the number of positively curved elements declines and the number of negatively curved synapses increases. There is no significant difference in the number of synapses with a straight active zone. The authors discuss possible functional consequences of the mentioned changes. PMID- 1754826 TI - [Presynaptic terminals in the sensorimotor area of the cerebral cortex in old laboratory rats]. AB - In male laboratory rats, Wistar strain, 2 and a half years old, quantitative morphometric analysis of synapses (type I after to Gray) from the second layer of the sensorimotor area of the neocortical region was performed. Evidence was provided of enlargement of the area of presynaptic formations, their circumference and of prolongation of the active zone of the synapse. The absolute number of agranular synaptic vesicles does not change, however, the number of vesicles per area unit declines (1 micron 2). This change was proved in all regions of the presynaptic ending. The enlargement of the area of synaptic endings is discussed in relation to possible shifts of water and electrolytes between the extracellular and intracellular space as a result of ageing of nervous tissue. The authors discuss also the passive change caused by a decrease of neuropil structures and narrowing of the extracellular space. The relative decline of the number of synaptic vesicles in the entire synapse and thus in the vicinity of the active zone is taken to be the morphological basis of a certain restriction of synaptic transmission in the sensorimotor area of the cortex in old age. PMID- 1754827 TI - [Proposal for a classification system for phagocytosis disorders]. AB - The presented classification is based on the modern view to the process of phagocytosis as evenements involving ligand-receptor interaction, transmission of signal through second messenger systems and activation of effector mechanisms leading to the specific cell behavior. According proposed classification, the phagocytic disorders are divided into extracellular disorders which are caused by abnormalities affecting ligands, and cellular disorders caused by pathological process affecting the phagocytic cell. These cellular disorders are subdivided into the defects of membrane receptors, the defects of enzymatic equipment and of subcellular structures. Laboratory investigation of phagocytic cells using several tests make possible to classify inborn, acquired, permanent as well as transient disorders into these groups. Examples of disorders in the each group are presented. This classification helps to clinicians make both diagnostic and therapeutic decisions. PMID- 1754828 TI - [Techniques of endoscopic treatment of malignant colorectal adenomas with respect to the subsequent prognosis of the patients]. AB - Since 1981 we detected in 45 patients (28 men, 17 women) 31 adenomas with severe dysplasia (ATD; formerly intramucous carcinoma) and 22 invasive carcinomas in the adenoma (IK penetrating beneath the muscularis mucosae). 95% of all findings were in the left colon before the lienal flexure. Patients with ATD were subjected only to endoscopic operation; of 22 of the subjects with IK 15 were recommended for surgery, and endoscopic treatment alone was provided to seven patients. Forty subjects were followed up on a long-term basis (on average for 34 months). Of 23 patients with ATD one female patient died from ischaemic heart disease, the remainder survive without signs of colorectal carcinoma. Of 17 subjects with IK followed up on a long-term basis five died (all after surgery as a result of generalization of the disease). All 7 patients with IK who had only endoscopic treatment survive without signs of relapse of the disease. In patients with ATD the authors consider EP as the definite therapeutic method, if it is feasible from the technical aspect. Patients with ATD and IK who were subjected to EP are checked after 6 weeks. A total coloscopic check-up is made subsequently in subjects with IK during the first year twice a year and in later years once a year, in subjects with ATD after annual intervals for a period of 5-6 years. PMID- 1754829 TI - [Ultrasonic findings in pancreas divisum]. AB - In 36 subjects with pancreas divisum an ultrasonic examinations of the pancreas were made after filling the stomach with 600 ml of fluid. In 27 subjects (75%) it was possible to evaluate the entire pancreas reliably, incl. the area of the dorsal segment. The gastric filling and positioning of the patients during examination improved in 47% the quality of the visualization, in particular in the left half of the pancreas. In three patients sonography revealed marked inflammatory changes in the entire gland. The applied examination procedure protracted the examination time of the pancreas to 30-40 minutes. Aimed ultrasonic examination with gastric filling is recommended as part of the examination procedure in subjects with pancreas divisum. PMID- 1754830 TI - [Risks of malignant neoplasms in workers in Czechoslovak uranium mines]. AB - The authors present a historical account on the findings which made it possible to define the most serious occupational disease in miners in uranium mines- bronchogenic carcinoma. In 1952-61 44 cases of lung cancer were reported in conjunction with radioactive substances, in 1962-85 already 1511 patients were recompensated. Z. Vich found in a prospective epidemiological survey that of 4803 workers who left for preventive reasons work places involving risk in 1968-75 20.5% died by 1985. The mortality rate from lung tumors was 3.5 times higher than in the male population of the Czech Republic. The authors analyze occupational risk indicators important for the prevention of this occupational disease. From the medical aspect the restriction of mining in uranium mines is welcome, as the work involves a high risk. PMID- 1754831 TI - [Group determination of 17-oxosteroids on thin-layer chromotography]. AB - 17-oxosteroids from human urine are measured by thin layer chromatography (Merck Kieselgel F-254 plates) with fluorometric detection at 310 nm (densitometer SHIMADZU CS-9000): 11-OH-etiocholanolone, 11-OH-androsterone + oxoetiocholanolone, oxoandrosterone, dehydroepiandrosterone and androsterone. Fluorescence of hydrazone derivatives after the reaction of steroids with dansylhydrazine represents the principle of the method. The recoveries of steroids added to human urine samples are 97-101.3% and the coefficients of variation are 0.78-11.77. PMID- 1754832 TI - [Consciousness and the electroencephalogram]. AB - In the course of 12 years the authors subjected to clinical EEG and stereo-EEG (SEEG) 72 patients (66 epileptics with the diagnosis of psychomotor epilepsy and grand mal) and six psychotic patients suffering from schizophrenia. With the exception of five epileptics and two psychotic patients all subjects had epileptic foci in the amygdalohippocampal complex (AHK). After coagulation of these foci marked improvement of the fits and the mental state occurred in half the patients. During EEG and SEEG recording the authors used different activation methods (hyperventilation through the nose and mouth, sleep, listening to music) and above all direct electric stimulation (ES) of one of the AHK. Secondary epileptic foci had, as a rule, more spikes and a lower threshold for ES than primary ones which contained more delta and slow theta waves. The ES led as a rule to an emotional response, such as anxiety and fear, more rarely to illusions, depersonalization and oneiroid hallucinations and twice to a hedonic response of non-sexual character. The purpose of ES was to assess the site from where it is possible to start the original aura or typical parox. The authors considered these foci, consistent with data in the literature, as the leading focus and it was subsequently coagulated. The authors investigated the reactivity and vigility by the patient's response to sound (the patient had to press a button) and by an interview with the patient. It was revealed that in isolated discharges of the spikes and waves in the scalp electrodes, i.e. in the neocortex, reactivity is lacking. In isolated discharges in the AHK the reactivity was satisfactory, but as a rule anxiety developed. It is thus possible to divide consciousness into emotional consciousness with its site in the AHK, i.e. in the limbic system, and rational consciousness which is a function of the neocrotical system. Congenital changes of consciousness such as vigility or sleep are described as "states" of consciousness. The rational or emotional aspect of behaviour is described as "type" of consciousness. Under normal conditions the states of consciousness alternate periodically and are sharply defined, the types of consciousness are closely linked and are difficult to separate. Under pathological conditions the "states" of consciousness differ less markedly and the "types" of consciousness are in dissociation. Thus obnubilation, depersonalization, illusions, pathic affects etc. develop, as a rule as part of the epileptiform or psychotiform syndrome. PMID- 1754833 TI - [Early differential diagnosis of tumors of the lesser pelvis using an appropriate combination of noninvasive and invasive methods]. AB - One hundred and twenty-three female patients were subjected to ultrasound and CT examinations on account of suspected tumours in the area of the lesser pelvis, or to evaluate the postoperative situation. Twenty-five patients were subjected in addition to the mentioned examinations also to angiography of the pelvic arteries. From comparison of the results of the radiodiagnostic examination and the surgical (histological) diagnosis ensues that in patients with a malignant tumour of the ovaries and uterus and with a benign tumour of the uterus the CT examination gives-more satisfactory results than the ultrasound examination. In patients with a benign tumour of the ovaries ultrasonic and CT examinations were approximately equally satisfactory. PMID- 1754834 TI - [Stomatologic care of patients with the Melkersson-Rosenthal syndrome]. AB - The authors describe the problems of diagnosis, treatment, prevention and dispensarization of patients suffering from Melkerson-Rosenthal's syndrome in a dental department. They describe in detail the manifestations of the syndrome in the orofacial area. Comprehensive dental care is based on studies of the pertinent literature and the authors' own experience. PMID- 1754835 TI - Transmission electron microscopic appearance of dentin matrix in type II dentin dysplasia. AB - Dentin matrix of demineralized primary and permanent teeth with type II dentin dysplasia was studied by transmission electron microscopy. The coronal dentin of a maxillary third molar exhibited a normal structure. In the radicular dentin, tubules were few in number; the major part of the dentin was composed of thick, curvy bundles of cross-striated collagen fibers. In the most aberrant areas of the radicular dentin, coarse collagen fibers measuring up to 140 nm in thickness were observed. The dentin of the primary tooth showed a similar, but somewhat less irregular, structure. PMID- 1754836 TI - Retrospective study of children with hypophosphatasia with reference to dental changes. AB - In the present retrospective study different dental and medical parameters have been analyzed in 17 Swedish children with established hypophosphatasia (HP). It was demonstrated that the basis for the establishment of the diagnosis varied among different dentists and physicians, and that the diagnostic parameters studied among the children varied. The most reliable parameters for HP included raised levels of phosphoethanolamine in urine, and clinical and radiologic findings associated with the legs. These findings were found among the children more often than lowered values of alkaline phosphatase in serum. Histologic analysis of an extracted tooth made a valuable diagnostic complement. It is concluded that a better diagnostic uniformity is recommended. In a well functioning collaboration with well defined tasks, both dentists and physicians can contribute to a reliable diagnosis. PMID- 1754837 TI - Column-like structures of human dentin in carious and artificial lesions. AB - Serial sections of 36 human teeth with minor to medium-sized carious lesions, adequate sections from previous studies of artificial lesions adjacent to fillings of amalgam (AM), silicate cement (SI) and glass ionomer cement (GI) were studied by ordinary light microscopy and microradiography. Six artificial primary root lesions were included. In carious lesions, dentin columns were visible in the demineralization zone and partly also in the translucent/radiopaque zone. A typical feature of the artificial lesions adjacent to SI fillings was highly radiopaque columns alternating with radiolucent ones. In the GI group such columns were seen at the cavity wall and the advancing front of the outer lesion. In the AM group dark columns were unveiled as pegs in the latter localization. The findings led to the assumption that the dark columns of intact dentin are preferred pathways of acid diffusion in artificial and, possibly, carious lesions. Increased radiopacity of columns in the SI and GI groups is explained by continued exposure of the tooth surface to fluoride dissolved from these fluoride rich filling materials. PMID- 1754838 TI - Effect of fluoride mouthrinsing on caries lesion development in shark enamel: an in situ caries model study. AB - Shark enamel consists of nearly pure fluorapatite and has been shown to demineralize in an in situ caries model. The present study was conducted to investigate whether additional fluoride supplementation in the form of mouthrinsing would inhibit lesion development in shark enamel. The study slabs of shark enamel were mounted in dental appliances. Six individuals wore the appliances while rinsing daily with a neutral 0.2% NaF solution for 4 wk. The specimens were analyzed by means of quantitative microradiography, and the data compared with a previous study using untreated shark enamel and the same participants. It was found that fluoride rinsing did not measurably inhibit enamel demineralization in 4 wk. Scanning electron microradiographs showed that calcium fluoride-like material was not formed on shark enamel after neutral fluoride treatment, supporting a previous study. The present study indicates, therefore, that formation of a calcium fluoride-like material on the enamel surface may be essential for the cariostatic effect of topical agents. PMID- 1754839 TI - Comparative antibacterial effects of chlorhexidine and stannous fluoride-amine fluoride containing dental gels against salivary mutans streptococci. AB - Forty-five young adults were divided into three groups of equal size and given a professional toothcleaning (3 times during 1 wk) with dental gels containing either chlorhexidine (CHX, 1%), or a SnF2-amine fluoride (AmF) combination (F- content 1.20%). The control group received toothcleaning with a placebo gel. The study was done double blind. The number of salivary mutans streptococci was monitored for 11 wk after the gel treatment using both mitis-salivarius bacitracin agar plates and the chairside method based on the adhesion of mutans streptococci on plastic strips (Dentocult-SM Strip mutans). Professional toothcleaning with a CHX gel was clearly most effective (P less than 0.001) but the baseline levels of streptococci returned in 11 wk. SnF2-AmF gel also reduced significantly (P less than 0.001) mutans streptococci but recolonization occurred already in 7 wk. Placebo gel, i.e. professional toothcleaning as such, did not show any statistically significant effect on the numbers of salivary mutans streptococci. None of the treatments affected the levels of lactobacilli or the total aerobic flora in saliva samples. Professional toothcleaning with a CHX gel, or with a SnF2-AmF gel, can be regarded as an alternative to the commonly used, but more patience demanding, application of gel in mouth trays at home for individuals with high caries activity. PMID- 1754840 TI - Ontogeny of class II antigen expressing cells in rat incisor pulp. AB - Class II antigen expressing cells are generally associated with the early phase of the immune response. Dendritic cells and macrophages expressing these cell surface antigens have recently been demonstrated and characterized in the dental pulp. The present study was undertaken to determine when the pulp receives its immunologic defense potential by examining the temporal appearance of class II antigen expressing cells in the rat incisor pulp. Pulp tissue specimens obtained at various time periods from a gestational age of 16 days to 14 wk after birth were examined by immunohistochemistry using O x 6 as a primary antibody and the ABC-technique. Comparisons were made with tissue samples from the spleen, intestine, skin and oral mucosa. At birth, all tissues, except for the pulp, presented cells expressing class II antigen with a dendritic appearance in a number and orientation resembling the mature tissue. A complete distribution of these cells was not seen in the dental pulp until 7 weeks following birth. Data show that the dental pulp acquires its ultimate structural arrangement of immune cells later than other tissues. PMID- 1754841 TI - Combined inhibitory effect of lactoferrin and lactoperoxidase system on the viability of Streptococcus mutans, serotype c. AB - We have studied the effects of iron-free lactoferrin (apo LF) and lactoperoxidase system (lactoperoxidase, LP/SCN-/H2O2), separately and together, on the viability of Streptococcus mutans (serotype c) in vitro. The bacteria were incubated in buffered KCl (pH 5.5) with and without the above components which were used at concentrations normally present in human saliva. Both apo LF and LP-system had a bactericidal effect against S. mutans at low pH. Together they showed an additive, but not a synergistic, antibacterial effect against S. mutans. Apo LF enhanced the LP enzyme activity but decreased the yield of the antimicrobial component, hypothiocyanite (HOSCN/OSCN-), when incorporated into the reaction mixtures. This decrease, which was most pronounced at low pH, was due to an LP independent reaction between apo LF and HOSCN/OSCN-. Our study indicates that the LP-system and apo LF can be combined to combat oral S. mutans. PMID- 1754842 TI - Protein composition of crevicular fluid before and after treatment. AB - Crevicular fluid (CF) analysis is a potential tool for site-specific diagnosis of periodontal disease activity. In this study, CF was collected using a novel washing method from 91 sites in 18 adult periodontitis patients both before and after conventional periodontal treatment. The sites studied were classified according to their clinical status and the number of polymorphonuclear leukocytes (PMN's) in CF samples. CF proteins were analyzed from individual sites with gel electrophoresis (SDS-PAGE). Furthermore, both the cell-bound and soluble neutral proteolytic activities of the samples were determined. Albumin was the main protein both in healthy and slightly inflamed sites. The most severely inflamed sites were characterized by high levels of low molecular weight (LMW) proteins (mol. weight ca. 12,000) and strong cell-bound neutral proteolytic activity. Scaling and root planing reduced both the LMW proteins and neutral proteolytic activity markedly in pockets responding well to treatment. The levels of the LMW proteins in CF correlated with the cell-bound neutral proteolytic activity, which reflected the number of PMN's in the sample. The present results suggest that the appearance of the LMW proteins in CF is associated with the periodontal inflammatory status of the site. PMID- 1754843 TI - Histoquantitative study of inflamed tongue mucosa. AB - A quantitative, semiautomatic analysis of histologic features of the specific inflammatory changes occurring on the dorsum of human tongue was made for 37 tongues. Well-documented histologic differences between clinically normal appearing tongue (control), atrophic, geographic and fissured tongue were shown quantitatively. The epithelium of atrophic tongue was thinner compared to the controls. Reduction of the thickness was due to the shortened or totally missing rete pegs. Epithelium of geographic and fissured tongue showed irregular rete pegs. In fissured tongue heavy inflammation seemed to shorten the rete pegs. In atrophic tongue the connective tissue was thicker compared to the controls. This could be due to mild, chronic inflammation causing loose connective tissue described in atrophic tongue. Muscle cells of geographic tongue appeared to be as in the controls, whereas in atrophic and fissured tongue the uppermost muscle cells were small and separated compared to the controls. PMID- 1754844 TI - Release of corrosion products from amalgam in phosphate containing solutions. AB - The effect of phosphate concentration on corrosion was compared for two types of amalgam: a conventional alloy (ANA 68) and a high-Cu admixed alloy (Dispersalloy). The test specimens were stored for 4 months in electrolytes containing 85 mM NaCl and 85 mM NaCl with 2.5, 10, or 100 mM phosphate buffer respectively. The solutions were renewed each month and analyzed for Cu, Zn, Sn, Hg, and Ag in an atomic absorption spectrophotometer. The surfaces and cross sections of the specimens were studied in a scanning electron microscope (SEM) with an energy dispersive detector (EDAX). The corrosion products, mainly Sn compounds, at the surface of the amalgams were less in the solutions containing high concentrations of phosphate. In cross-section subsurface corrosion of the high-Cu amalgam was observed especially in specimens immersed in the NaCl solution without phosphate. The conventional amalgam showed surface corrosion only. The decrease in release of elements with time from the conventional amalgam in all the experimental solutions might indicate passivation. For the high-Cu amalgam the release of elements increased with time, except for Cu and Sn in the solution with 100 mM phosphate, indicating that phosphate inhibits corrosion of the Cu-Sn-phases. Release of corrosion products from the high-Cu amalgam was more dependent on the presence of phosphate than the conventional amalgam. PMID- 1754845 TI - European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA). PMID- 1754846 TI - Helicobacter pylori infection and non-ulcer dyspepsia: the effect of treatment with colloidal bismuth subcitrate. AB - A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia (NUD) and to determine the efficacy of colloidal bismuth subcitrate (CBS) in the treatment of NUD. Seventy-one patients were randomly allocated (double blind) to CBS or placebo, two tablets twice daily for 4 weeks. The severity of dyspepsia was scored and endoscopies performed before and after treatment, and antral biopsy specimens were taken for bacteriologic and histologic examination. Forty patients had H. pylori infection, and all had changes of chronic active gastritis. H. pylori was cleared from 17 to 21 patients (81%) treated with CBS, whereas none of the 19 patients treated with placebo cleared the bacteria. Improvement in histology was noted in 15 of 21 patients (71.4%) treated with CBS, whereas no improvement was noted in any of the placebo controls. Thirty-one patients were negative for H. pylori. All had either normal gastric histology or minor degrees of inflammation. Seventeen of these patients received CBS, and 14 received placebo. All groups reported improvement in the symptom score; however, the H. pylori-positive, CBS-treated group recorded a significantly higher improvement than the other groups (p less than 0.001). Relapse of H. pylori infection after initial clearance of the bacteria was high. Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS. PMID- 1754847 TI - Clogging and other complications of endoscopic biliary endoprostheses. AB - This study included 236 patients treated with endoscopic biliary endoprostheses. Malignant strictures were responsible for the obstruction in 87% of the patients. The 1-week and 1-month mortality for patients with malignant strictures was 10% and 22%, respectively, whereas that of patients with benign conditions was 3% and 10%, respectively. The major complication encountered was the frequent hospital readmissions of patients owing to clogging of their endoprostheses. Late clogging had an overall occurrence of 33% and presented with recurrence of jaundice with or without fever or pain. Late signs of cholangitis occurred in 15% of the patients, whereas other late complications were rather infrequent. Although 10 french endoprostheses had a significantly longer patency period than 7-french- that is, 6 months versus 2 months (p = 0.01)--the proportion of patients in whom clogging occurred was nearly the same, 30% for 10-french and 32% for 7-french endoprostheses. PMID- 1754848 TI - Clogging of biliary endoprostheses. A morphologic and bacteriologic study. AB - The main problem encountered with the use of biliary endoprostheses is their tendency to clog, which necessitates their exchange. We studied this problem by performing light and electron microscopy and bacterial cultures on both unused and clinically used endoprostheses. These examinations showed several basic defects in their manufacture, such as irregular inner surfaces and badly constructed side holes. The deposit that ultimately led to their occlusion was found mainly to be concentrated around the side holes. Minimizing the amount of material, bacteria, and plant fibres adhering to the endoprosthesis is the desired goal and may be achieved by improving their manufacture and design. PMID- 1754849 TI - Effects of nocloprost on gastric functions in man. AB - Previous studies in animals and humans demonstrated that nocloprost, a stable prostaglandin E2 analogue, shows very high gastroprotective potency, relatively weak gastric inhibitory activity, and low systemic bioavailability after oral administration. In this study the effects of nocloprost on gastric acid secretion and intraluminal pH and on gastric emptying and plasma gastrin levels were determined in humans. Nocloprost at doses of 50 and 100 micrograms was ineffective, but at a dose of 200 micrograms it reduced the response to pentagastrin significantly and that to a peptone meal by 30-50% and abolished plasma gastrin response without affecting the rate of gastric emptying. Nocloprost given at a dose of 100 micrograms three times daily 30 min before the major meals (breakfast, lunch, and dinner) did not affect intragastric pH significantly as monitored by continuous intraluminal pH-metry. We conclude that nocloprost does not affect gastric acid secretion or intraluminal pH when applied at a dose (50-100 micrograms) that is gastroprotective and that is proposed for peptic ulcer therapy. A higher dose (200 micrograms) of nocloprost causes moderate gastric acid inhibition and suppression of plasma gastrin release without affecting gastric emptying or causing any side effects. PMID- 1754850 TI - Availability of energy substrates during liver regeneration in malnourished rats. AB - A retarded liver regeneration rate during malnutrition has previously been reported. To explore the mechanisms, some energy substrates were studied during liver regeneration and malnutrition. Forty-one rats were allocated to one of three groups (G): GI were normally nourished rats, which were partially hepatectomized; GII were semistarved rats, which were partially hepatectomized; and GIII were normally nourished rats, which were sham-operated. Biopsy specimens were taken from the liver at the time of partial hepatectomy and when they were killed after 48 h of regeneration. The samples were analysed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), glycogen, lactate, and pyruvate, and energy charge potential (ECP) was calculated. ATP, ECP, and glycogen levels were decreased in the malnourished group before the resection. After 48 h of regeneration all values were unchanged in the normally nourished group, whereas ATP, ADP, and ECP were increased in the malnourished group compared with the initial values. The lactate/pyruvate quotient was increased in malnourished rats compared with normal rats. The results suggest that the energy supply is not a limiting factor for the reduced regeneration rate seen in malnourished animals. PMID- 1754851 TI - Diagnostic accuracy of ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography in the detection of obstructive jaundice. AB - The purpose of this prospective study was to investigate the diagnostic accuracy of ultrasound (US), computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) in the distinction between extrahepatic and intrahepatic causes of jaundice. The limit for the inclusion to the study was defined as a serum bilirubin concentration greater than or equal to 40 mumol/l. Altogether 187 jaundiced patients were studied. The sensitivities of US, CT, and ERCP were 63%, 77%, and 87%, respectively. The differences between all these methods were statistically significant. The specificities and positive predictive values were high, reaching 96-99%, but the negative predictive values were low, ranging between 38% and 60%. Choledochal stone disease constituted the main etiology of false-negative studies in all investigations. Imaging procedures have a prominent role in the diagnostic study of the jaundiced patient, but it is obvious that their diagnostic accuracy may vary between institutions because of the variance in local experience and expertise, and because of the differences in diseases causing jaundice. PMID- 1754852 TI - Radiographic evidence of cholecystokinin octapeptide receptors in the hamster gallbladder. AB - The distribution of cholecystokinin receptors in the hamster gallbladder was investigated by 125I-labeled Bolton-Hunter-cholecystokinin octapeptide autoradiography. Light microscopic examination showed a marked accumulation of radiolabeled cholecystokinin within the domain of the muscle layer of the gallbladder. The electron microscopic study further disclosed the presence of radiolabeling mostly in those areas corresponding to cell-to-cell junctions of smooth-muscle cells. Our results suggest that contraction of the gallbladder may primarily be induced by cholecystokinin interacting with its specific receptor in smooth-muscle cells. That cholecystokinin receptors were more abundant in the junctional complexes of smooth-muscle cells suggests that cholecystokinin may have a major role in muscle contraction of the gallbladder, which eventually produces an effective bile emptying. PMID- 1754853 TI - Increased levels of fibrinolysis reaction products (D-dimer) in patients with decompensated alcoholic liver cirrhosis. AB - We studied the activation of coagulation and fibrinolysis in the blood of patients with compensated (n = 25) and decompensated (n = 25) liver cirrhosis. We observed increased blood concentrations of thrombin-antithrombin III (TAT) complexes (p less than 0.001) and of D-dimer (p less than 0.001) in both groups of patients compared with healthy volunteers (n = 25). The blood levels of tissue type plasminogen activator (t-PA) activity (p less than 0.001) and the concentrations of t-PA antigen (p less than 0.001) were also significantly raised in both groups of patients compared with controls, whereas plasminogen activator inhibitor did not deviate. There were no significant differences in the determined variables between the two groups of patients except that the concentrations of D-dimer were significantly higher (p less than 0.001) in patients with decompensated liver cirrhosis. The ratio between D-dimer and TAT did not deviate between patients with compensated liver cirrhosis and healthy volunteers but was significantly increased in patients with decompensated liver cirrhosis. These observations indicate that efflux from the extravascular space (for example, ascitic fluid) contributes to the high concentrations of fibrin degradation products (D-dimer) in patients with decompensated liver cirrhosis. In addition, we conclude that patients with liver cirrhosis have an enhanced activation of both coagulation and fibrinolysis but that the balance between these two systems is not significantly displaced compared with healthy volunteers. PMID- 1754854 TI - Adhesion of Helicobacter pylori to human gastric mucosal biopsy specimens cultivated in vitro. AB - The therapeutic advances in Helicobacter pylori infection is hampered by the lack of suitable animal model systems. We have previously reported on successful adherence of H. pylori to pig gastric mucosa cultured in vitro. The aim of this study was to verify the technique in human biopsy specimens cultured in vitro. Mucosal samples were taken from H. pylori-negative and H. pylori-positive patients undergoing gastric surgery. The non-infected tissue was infected with H. pylori in vitro, and the infected tissue was put into culture immediately. Total number and those H. pylori firmly attached were checked throughout a 72-h culture. Viability of cultured human gastric mucosa was good and unaffected by the presence of H. pylori. The amount of bacteria adhering, increased with time from 0.01% to 2-4% after 72 h in culture. In vivo-infected specimens initially had a low number of firmly attached H. pylori, but total H. pylori increased with time in culture. It is concluded that human gastric biopsy specimens show good viability for 72 h and that viability and cell division of H. pylori were maintained in both in vivo and in vitro H. pylori-infected tissue. In both cases the total number of viable bacteria attached to the specimens increased with incubation time. PMID- 1754855 TI - Importance of measuring plasma thrombin-antithrombin III complex levels when using antithrombin III concentrate therapy in fulminant hepatic failure. AB - We investigated changes in the concentrations of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2 plasmin inhibitor complex (PIC) after the intravenous administration of 4000 units of antithrombin III (AT III) concentrate to patients with fulminant hepatic failure (FHF), subacute hepatitis (SH), or liver cirrhosis (LC). FHF patients showed shortening of the initial half-life of exogenous AT III. In addition, a marked rise in plasma TAT was noted 3 to 6 h after the intravenous administration of AT III, even in patients who had a normal plasma TAT level before AT III therapy. In contrast, SH and LC patients showed no marked changes of plasma TAT levels after AT III administration. No marked changes were observed in the PIC concentration in any of the patients. These findings suggest that thrombin formation is increased in FHF and that simple measurement of the plasma TAT concentration is not an adequate method for assessing thrombin formation in FHF patients who have suspected disseminated intravascular coagulation associated with an apparent decrease in AT III synthesis. Instead, it seems necessary to measure the plasma TAT concentration in FHF patients after replacement therapy with AT III concentrate has been performed, to evaluate their hypercoagulability more accurately. PMID- 1754856 TI - Endoscopic follow-up study of gastric ulcer to detect malignancy: is it worthwhile? AB - Endoscopic follow-up study of gastric ulcer to detect cancer is held to be mandatory. To evaluate the benefits of this routine strategy, 913 index endoscopies for gastric ulcer in 773 patients during the 3-year period 1985-87 were analyzed. Correctness of diagnosis was verified through surgery, autopsy, or clinical follow-up. Endoscopic follow-up was done in 83% of the cases, totaling 1269 endoscopies, showing gastric cancer in 10 patients. Clinical outcome, however, was poor for five of these (early death). Five additional cancer cases were missed by the endoscopic follow-up. In the same period 63 gastric cancers were found at the first endoscopy; 9 of these were diagnosed through biopsies only. Predictive values of the macroscopic judgements of benign lesion or probable/definite malignancy were 0.98 and 0.40, respectively. Evaluation of case records did not indicate characteristics that would have helped in the correct differentiation between benign and malignant lesions. Thus, each case of curable gastric cancer is found at the expense of approximately 250 follow-up endoscopies. We are in need of sensitive and specific markers for possible malignancy in the patient with apparently benign gastric ulcer. PMID- 1754857 TI - Anaesthetic agents suppress basal and stimulated gastric acid secretion. Are intramural neurons involved? AB - Anaesthetized animals are often used in studies of gastric secretion. We have examined the effect of anaesthetics on the acid output in gastric fistula rats and pylorus-ligated rats, both vagally intact and denervated. Diethyl ether, chloral hydrate, and mebumal effectively reduced both basal and stimulated acid output in fistula rats. The acid output in pylorus-ligated rats was greatly reduced by the anaesthetics. In vagally denervated rats local nervous reflexes are thought to play an important role in the acid secretory response to pylorus ligation. Anaesthetic drugs suppressed acid output in both vagally intact and vagally denervated rats. The possibility of an action on intramural neurons cannot be excluded. The neuro-suppressive effect of anaesthesia should be considered in studies of gastric acid secretion. PMID- 1754858 TI - Dental plaque: a permanent reservoir of Helicobacter pylori? AB - The aim of the study was to observe the relationship between the two reservoirs of Helicobacter pylori--that is, dental plaque and the stomach. With the Campylobacter-like organism (CLO) test, H. pylori was detected in dental plaque and in gastric antral and body mucosa in 98%, 67% and 70%, respectively, of 43 consecutive patients with dyspepsia. The rapidity of the CLO test indicates that the density of H. pylori is heaviest in dental plaque, less in the antrum, and least in the body mucosa of the stomach. Triple drug therapy (bismuth, tinidazole, and amoxycillin or doxycycline) was administered for 15 days to 24 patients. By the CLO test, H. pylori was eliminated from the gastric mucosa in all 24 patients but persisted in dental plaque in all of them. Our observations indicate that dental plaque is unaffected by triple drug therapy and is perhaps a permanent reservoir of H. pylori if local therapy also fails to eradicate the organism. PMID- 1754859 TI - Ranitidine for non-ulcer dyspepsia. A clinical study of the symptomatic effect of ranitidine and a classification and characterization of the responders to treatment. AB - Seven Norwegian centres recruited 61 female and 54 male patients with non-ulcer dyspepsia (NUD). Their mean age was 40 years. After 6 weeks' double-blind alternating treatment with 150 mg ranitidine twice daily and placebo, 1 week of each alternative (part I), an effect score (Xs) and an efficacy index (Ei) were calculated. Ranitidine was significantly superior to placebo for symptomatic relief (p less than 0.01). Twenty-eight, 49, and 38 patients were Xs-classified as 'responders', 'unclassified', and 'nonresponders' to ranitidine, respectively. The symptomatic effect was impressive in the responder group and moderate but significant also in the unclassified group. The nonresponders had a significantly unfavourable effect of ranitidine compared with placebo. The Xs-classified responders and unclassified continued single-blind treatment with ranitidine for 4 weeks (part II) and were reclassified as 'new responders/nonresponders'. The new responders received single-blind treatment with placebo until relapse or maximum 8 weeks (part III). Parts II and III verified the good Xs classification of responders to ranitidine treatment. The overall effect of ranitidine in patients with NUD was due to good symptomatic effect in a subpopulation characterized by meal-related heartburn and/or regurgitation, large body mass index, first-degree relatives with gastrointestinal diseases, a relatively low frequency of gastrointestinal symptoms per week, and absence of soft stools. PMID- 1754860 TI - [Cardiovascular risk factors--an integrated sympathetic viewpoint]. AB - A large body of experimental and clinical data concerning the "classical cardiovascular risk factors" may be integrated into a unifying concept in which an increase in sympathetic activity and nutritional factors play a crucial role. The enhancement of sympathetic activity (e.g. as a consequence of psychosocial stress), induces--via direct and indirect mechanisms--activation of the renin angiotensin-aldosterone system and the insulin axis. Balanced endothelial function may also be disrupted. Subsequently, these alterations lead to cardiovascular remodelling and development of the early stages of arteriosclerosis. Mechanical forces such as pressure and strain, and also mild hyperinsulinemia with secondary elevations in the LDL/HDL ratio further amplify these processes. Wrong nutrition, characterized by an elevated salt, sugar and fat intake, further stimulates these pathological events. The chain of events finally leading to the clinical manifestation of arteriosclerosis is certainly strongly based on, and modified by, a genetic predisposition. Cigarette smoking acts as a pulsatile, exogenous amplifier of the sympathetic nervous system. Furthermore, complex interactions of the various "hormonal risk systems", namely renin-angiotensin, insulin, and LDL/HDL cholesterol, have been observed at the cellular and molecular level. These interactions are integratively influenced by environmental and sympathetic factors. Therefore, a comprehensive approach should be incorporated into prophylactic and therapeutic strategies. PMID- 1754861 TI - [Can drugs, especially calcium antagonists, bring about regression of atherosclerosis, especially coronary sclerosis?]. AB - The feasibility of true regression of human atherosclerotic plaques (reduction in volume) through drug therapy is still debated; the increase in coronary artery diameter, especially eccentric stenoses during massive reduction of serum cholesterol, can also be due to stabilization of endothelial function and improvement of the abnormally raised basal coronary tone. Today, there are two groups of substances with anti-atherosclerotic properties: lipid-lowering drugs, and calcium-entry blockers. As evidenced both from animal experiments and prospective studies in man by quantitated coronary angiography (QCA), the latter act mainly by retarding the evolution of new plaques, and possibly even of fatty streaks. In man, four studies with calcium-entry blockers so far exist, all demonstrating a significant reduction (average -46%) of new lesions (stenoses and occlusions) in previously angiographically normal segments. To what extent these favourable anatomical results will lead to an improvement of cardiac events caused by plaque rupture (unstable angina, myocardial infarction) later on is still an open question. The slow anatomical progression of coronary artery disease, as evidenced by prospective repeated QCA, calls for studies with long term follow-ups (10 and more years) and large numbers of patients. PMID- 1754862 TI - [The internist--a many-sided profession]. AB - "Internal medicine" in the USA, and "general medicine" in the UK, are increasingly assuming the form of basic medical knowledge with a view to subsequent specialization. In Switzerland, three types of practising internists or physicians (in the strict sense) can be described: the internist as general practitioner, the general internist with a main centre of interest, and the subspecialist. Continuing medical education must take these manifold aspects of the profession into account. For practising physicians, joint meetings of internists of the second and third types are desirable, on the lines of those for physicians in the major hospitals. PMID- 1754863 TI - [Internal medicine: problems and perspectives]. AB - The professional status of the internist is changing. For instance, subspecialists and general practitioners are conducting more and more the traditional activities of internists. The number of certifications in general internal medicine in Switzerland over recent years has decreased. The same phenomenon is observed in other countries and particularly the USA, where surveys show unquestionable disappointment among internists with the quality of their working life arising from concerns over a private life-invading profession, low income, increasing administrative burdens and loss of clinical decision-making autonomy. Has the internist still a place in our health care system, and what would be the effect of disappearance of internists on the quality and the costs of medicine? The Swiss Society of Internal Medicine seems unable to solve this disaffection problem unaided, since it also interests general practitioners and consequently all the disciplines oriented toward primary care and family medicine. PMID- 1754864 TI - [Quality of treatment in hypercholesterolemia in ambulatory patients]. AB - In 1989 serum cholesterol was determined as a routine procedure in 534 consecutive patients. The response of the physicians to elevated cholesterol levels and factors associated with a treatment decision were analyzed. A follow up was obtained in treated patients after at least one year. 105 patients (20%) had hypercholesterolemia, 84 of whom were available for evaluation; only in 34 (40%) was treatment initiated. Patients were more likely to be treated (p less than 0.05) if they had cholesterol greater than 1 mmol/l above normal, if they were between 41 and 50 years old, and if cholesterol had been determined at the physician's special request. The decision to treat was not influenced by sex, presence of further risk factors or by manifest atherosclerosis. After one year, 11 of 26 patients were still well controlled and treated. Their mean cholesterol level was significantly lower as compared to pretreatment levels. We conclude that initial as well as long-term management of patients with hypercholesterolemia should be improved. PMID- 1754865 TI - [Late results following surgical repair of aneurysm of the descending thoracic aorta]. AB - A consecutive series of 74 patients was analyzed after repair of descending thoracic and thoracoabdominal aortic aneurysms. After hospital discharge there were 13/71 deaths (18%) during a mean follow-up of 60 +/- 20 months (range: 28 107). Actuarial analysis showed a mean survival rate of 89% after 1 year, 78% after 5 years and 71% after 9 years. During the same time period there were reoperations of the aorta in 10/71 patients (14%). Actuarial analysis showed freedom of reoperation in 97% after 1 year and in 80% after 5 years. Elective repair of these aneurysmal lesions can be recommended. PMID- 1754866 TI - [Are ECG criteria for indications for thrombolysis in acute myocardial infarct defined too narrowly?]. AB - BACKGROUND: Despite the advantages of fibrinolytic therapy in acute myocardial infarction only about 20% of these patients receive this therapy. We studied patients excluded from fibrinolysis to identify subgroups with high mortality, which could derive benefit from more liberal interpretation of the indications for fibrinolytic therapy. METHODS: Retrospective chart review to identify patients with acute myocardial infarction in our coronary care unit 7/88-7/89. All patients received a questionnaire one year after this myocardial infarction. Patients not answering the questionnaire were contacted by phone or the information was sought from their physician. Indications for thrombolysis (with streptokinase or rTPA) were ST elevations of greater than or equal to 2 mm in greater than 2 adjacent leads and the absence of contraindications. RESULTS: In 231/242 (95%) of the identified patients a complete follow-up was obtained, 32% were age greater than 70 years, 30% were admitted greater than 6 h after the beginning of the symptoms, 64% did not fulfil the ECG criteria for thrombolysis, 21% (49/231) received thrombolytic therapy. The mortality after one year was 20.3% in patients not treated with thrombolysis and 8.2% in patients with thrombolysis (difference 12.1%, 95% confidence interval 2.9-21.3%, p = 0.048). Patients with preceding old infarctions (n = 58) fulfilled the ECG criteria for thrombolysis in a significantly smaller proportion (21% vs 41%, p = 0.004). Of all patients 12% were excluded from thrombolytic therapy due to a negative initial ECG and yet developed a Q ware infarction. The one year mortality of patients not given thrombolysis and with a Q wave infarction was 24% (22/93, p = 0.02 as compared to patients with thrombolysis), in patients with non Q wave infarction it was 13% (11/82, p = 0.41) and in patients with ambiguous ECG it was 57% (4/7, p = 0.006). The mortality in patients with a preceding infarction was 31% and significantly higher than in patients with a first infarction (16%, p = 0.049) and in patients receiving thrombolysis (8.2%, p = 0.005). CONCLUSIONS: By excluding patients with acute myocardial infarction from thrombolytic therapy a group with high first year mortality is selected. Most patients are excluded because of an initial ECG not showing enough ischemia to fulfil the criteria for thrombolytic therapy. A prospective study of thrombolytic therapy using less rigid ECG criteria in the subgroups with the highest mortality (patients with preceding myocardial infarction or ambiguous ECG) seems necessary. PMID- 1754867 TI - [Glomerular hyperfiltration following unilateral nephrectomy in healthy subjects]. AB - 23 living related kidney transplant donors were prospectively studied to determine the degree of hyperfiltration which occurs after uninephrectomy and to monitor potential consequences of this procedure such as hypertension, microalbuminuria or renal functional impairment. Standard inulin and PAH clearance studies were performed immediately before (n = 23), one week after (n = 22) and one year after nephrectomy (n = 12). Hyperfiltration was defined as the ratio of (post-nephrectomy inulin clearance)/(0.5 x pre-nephrectomy inulin clearance), hyperperfusion was defined in an analogous way for PAH clearance. One week after uninephrectomy, hyperfiltration averaged 134 +/- 6% (SEM) and hyperperfusion was 138 +/- 6%. The degree of hyperfiltration did not correlate with donor age. One year after nephrectomy, hyperfiltration was nearly unchanged (130 +/- 7%) whereas hyperperfusion had significantly decreased to 119 +/- 8% (p less than 0.05). Blood pressure did not increase after nephrectomy and no new cases of hypertension were observed during follow-up. In contrast, there were two new cases of microalbuminuria at one week and one year after nephrectomy. Further follow-up of these kidney donors is warranted. PMID- 1754868 TI - [Randomized, double-blind comparison of isosorbide-5-mononitrate and delayed action nifedipine in patients with stable exertional angina. Multicenter Study Group]. AB - The therapeutic effects of IS-5-MN and s.r. nifedipine were investigated in this double-blind, randomized, group-comparative, multicenter study over 2 weeks, in 251 patients with stable reproducible exercise-induced angina. After 2 weeks' treatment with IS-5-MN 20 mg b.i.d. or t.i.d., 61% of the patients were responders who showed an increase in total exercise time (to moderately severe angina) of greater than or equal to 20% in comparison with placebo in the run-in phase. The corresponding responder rate after s.r. nifedipine 20 mg b.i.d. or 40 mg b.i.d. was 53%. Both IS-5-MN and s.r. nifedipine significantly increased the total exercise time, the time to angina onset and to greater than or equal to 1 mm ST-depression, and significantly reduced the rate pressure product and the ST segment depression at peak exercise in comparison with placebo in the run-in phase. The improvement in quality of life as indicated by the reduction in anginal episodes and intake of short-acting nitrates was comparable with both drugs. The pattern and incidence of all AEs were as expected in the two active treatment groups. The daily treatment costs for a 20 mg b.i.d. dosing regimen for both drugs in the Federal Republic of Germany was 64% higher for s.r. nifedipine than with IS-5-MN. PMID- 1754869 TI - [Variations in body weight and feeding behavior in internal medicine]. AB - We have identified an eating disorder in 13% of women hospitalized on a medical ward for various reasons. These as well as obese patients undergo wide fluctuations of weight sometimes exceeding 30% of their present weight. Surprisingly, even in the absence of eating disorders, the changes in weight during adulthood are marked (22% of present body weight). Weight history should be included systematically in the medical history, since it can underscore concern over weight or even an unrecognized eating disorder. PMID- 1754871 TI - Beyond sympathy. Growth factors may help heal stubborn wounds. PMID- 1754870 TI - [Central analgesic effects of antidepressant drugs with various mechanisms of action: desipramine, fluvoxamine and moclobemide]. AB - Analgesic properties of antidepressants are not yet well established. The aim of this study was to investigate the analgesic effect of three antidepressants after single oral dose administration to healthy volunteers. The late spinal R-III reflex threshold (objective pain threshold) and the subjective pain threshold (numerical categorical scale) were markers of analgesic effect. Desipramine induced significant increases in both thresholds. Fluvoxamine and moclobemide also exerted a significant analgesic effect, although displaying distinct patterns depending on the analgesic marker considered. Antidepressants exert a central analgesic effect independent of their antidepressive effect and, depending on their mode of action, already detectable at spinal level. PMID- 1754872 TI - Fatal flaw. Who will have the right to examine your genes? PMID- 1754873 TI - Cross reaction. Could AIDS really be an autoimmune disease? PMID- 1754874 TI - Homeless families. PMID- 1754875 TI - Levels of copper in the urine of women from nonpolluted farming regions of Japan. AB - Nearly 1500 spot urine samples were collected in the winter of 1987-1988 from women of seven farming prefectures located throughout Japan. Samples were analyzed for copper by flameless atomic absorption spectrometry. The copper content of the urine samples (Cu-U) distributed log-normally with a geometric mean (geometric standard deviation) of 36.9 (1.47) micrograms/l after adjustment for the specific gravity of urine of 1.016. The 95% confidence range was 17.1 79.7 micrograms/l. Neither alcohol consumption nor smoking habit affected the Cu U. A literature survey showed that the observed level appears to be somewhat higher than previously reported values. PMID- 1754876 TI - Cadmium kinetics in freshwater clams (Unionidae) under field and laboratory conditions. AB - Cadmium dosing experiments were carried out with the freshwater clam Unio pictorum in flow-through micro-streams in order to obtain additional information on the kinetics of cadmium accumulation and elimination. Accumulation of cadmium in the kidney was rapid and within 3 weeks a concentration factor of 6000 was found. During elimination (29 weeks), the organs lose about one-third of their cadmium content rather rapidly, but no further elimination occurs. It can be concluded that the process of Cd accumulation is rapid and almost irreversible. PMID- 1754877 TI - Mercury in muscle tissue of lesser-spotted dogfish (Scyliorhinus caniculus L.) from the north-east Irish Sea. AB - This paper reports concentrations of mercury in muscle tissue of lesser-spotted dogfish (Scyliorhinus caniculus L.) from various locations within Liverpool Bay and the north-east Irish Sea. Concentrations of mercury in fish muscle showed distinct spatial variation, with values from the northern sectors of the Irish Sea significantly lower than those for the southern area, particularly sites in Liverpool Bay and around the mouth of the Mersey Estuary. The data support the hypothesis that there are several major populations of lesser-spotted dogfish within the study area, each of which remains quite distinct during seasonal movements. Consequently, exposure to environmental mercury is reflected in muscle concentrations of mercury. Regressions of mercury concentration against fish length showed significant relationships for the majority of sites, with the slope relating to distance from known sources of mercury contamination. Mean mercury concentrations were higher than in corresponding populations of flatfish from the same areas. PMID- 1754878 TI - Sweat lead levels in persons with high blood lead levels: experimental elevation of blood lead by ingestion of lead chloride. AB - Blood lead levels were experimentally elevated in two subjects by ingestion of single oral doses of lead as lead chloride. Serial samples of blood, urine and sweat were collected subsequently. Sweat samples were collected in polythene armbags while subjects cycled on a bicycle ergometer in a hot chamber. In spite of increases in blood and urinary lead levels, no increases in sweat lead levels were recorded. Possible reasons for this observation are discussed. PMID- 1754879 TI - Levels of aldrin and dieldrin in environmental samples from Delhi, India. AB - Aldrin and dieldrin residues in soil, earthworms, water, fish and clams from different sites in Delhi were monitored. Concentrations of aldrin and dieldrin were found to be higher in earthworms than in soil. Concentrations of dieldrin were higher in fish than the ambient water, but the concentration of aldrin in the ambient water was the same as that in fish and clams. PMID- 1754880 TI - Fate and microbiological effects of furazolidone in a marine aquaculture sediment. AB - Furazolidone is used in the treatment of bacterial diseases in farmed fish. During application a large proportion of the administered drug reaches the environment directly or via feces. The persistence and metabolism of furazolidone in sediment from a Norwegian salmon farm is described. Furazolidone, in contrast to oxytetracycline and oxolinic acid, is actively metabolized by microorganisms in the sediment. The main metabolite is 3-(4-cyano-2-oxobutylidene-amino)-2 oxazolidone. This is a well known metabolite of the degradation of furazolidone in mammals, fish and Escherichia coli. 3-(4-Cyano-2-oxobutylideneamino)-2- oxazolidone had no detectable antibacterial activity. The half-life of furazolidone in the sediment at 4 degrees C was calculated to be 18 h. PMID- 1754881 TI - Epidemiology of postoperative deep vein thrombosis and pulmonary embolism. PMID- 1754882 TI - Pathophysiology of venous thromboembolism. AB - Venous thromboembolism is complex with a multifactorial etiology. The Virchow triad (changes in blood flow, changes in vessel wall, and changes in the properties of blood) gives the main factors involved in venous thromboembolism. Venous stasis during immobilization in general anesthesia, stroke with hemiparesis, and heart failure plays a central role. The thromboembolic process can be initiated by a disturbance in the normal "hemostatic balance," with an increased thrombogenic potential, due to release of thromboplastin and collagen exposure during vessel wall injury by stasis and hypoxia, decreased fibrinolysis during surgery, malignancy, among others. Many substances modify these processes, including heparan sulfate, AT III, protein C, t-PA inhibitor, and alpha 2 antiplasmin. PMID- 1754883 TI - Principles of thromboprophylaxis in surgical patients. AB - Thromboprophylactic treatment during surgery reduces mortality and morbidity. The type of prophylaxis may be individualized according to type of operation and presence of major risk factors, such as prior thromboembolism, malignancy, long duration of immobilization, and medical conditions. All patients over the age of 40, or even younger, who have major risk factors, and whose operations will last for more than 1 hour, may benefit from thromboprophylaxis. Available prophylactic methods allow for treatment with an acceptably low level of side effects and economic cost, when compared with the cost of diagnostics and treatment of thromboembolism. PMID- 1754884 TI - Diagnosis of venous thrombosis. PMID- 1754885 TI - Mechanical prophylaxis of deep vein thrombosis. PMID- 1754886 TI - Clinical assessment of venous thromboembolic risk in surgical patients. AB - Prophylaxis against postoperative venous thromboembolism should be tailored according to the patient's level of risk. However, risk assessment is not yet in widespread use in surgical practice. In this study, 538 general surgical patients were prospectively assessed based on a scoring system containing 20 risk factors. Depending on the total risk factor score, the patients were grouped into low (0 to 1, 34.5%), moderate (2 to 4, 48.5%), or high risk (more than 4, 17.2%) categories. Statistically significant (p less than 0.0001) correlation was found between our results and those of three existing risk assessment systems. Overall, of the 538 patients, 37.2% received prophylaxis; 10%, 42.1%, and 76% received prophylaxis in the low-, moderate-, and high-risk categories, respectively. Mechanical prophylactic modalities (graduated elastic compression and sequential intermittent compression) were preferred over pharmacologic modalities. These results suggest that implementation of prophylaxis remains underutilized despite published reports, including NIH guidelines. Our results indicate that the majority of surgical patients seen in this suburban hospital have two or more risk factors for developing venous thromboembolism. PMID- 1754887 TI - Venous thromboembolism prophylaxis and risk assessment in medical patients. AB - In summary we have developed a VTE risk assessment system for medical patients based on our prior experience in surgical patients. In this model we divide individuals into low, moderate, and high-risk categories. We realize that our system needs further validation with appropriate diagnostic endpoints to correlate the actual occurrence of venous thromboembolism with the predicted risk on the basis of our score system. Nevertheless, the proposed model reflects one approach to achieving a prophylaxis tailored to the patients' risk. PMID- 1754888 TI - Interpretation of the lung scan. PMID- 1754889 TI - Deep venous thrombosis and pulmonary embolism. PMID- 1754890 TI - The problems of the clinical and laboratory diagnosis of pulmonary embolism. AB - Suspecting and diagnosing venous thrombosis and pulmonary embolism remain major clinical problems. For a variety of reasons, including the patient's pre-existing cardiac and pulmonary status and the release of humoral mediators, pulmonary emboli evoke varied responses in different patients. Symptoms and signs of pulmonary embolism are not specific; they depend on the size and the hemodynamic and humoral consequences of the embolus. Conversely, they may not be present at all. Chest radiographic and electrocardiographic findings are nonspecific, and may be most helpful in establishing the presence of other conditions that may be confused with pulmonary embolism. Arterial blood gases can only heighten the suspicion of pulmonary embolism; they should never be used to exclude the diagnosis. Clinical and laboratory findings therefore do not diagnose pulmonary embolism; rather, they raise the level of concern and set the stage for the performance of subsequent diagnostic studies. PMID- 1754891 TI - Lung scanning in the diagnosis of pulmonary embolism: the emperor redressed. AB - Diagnosis and management of the patient with pulmonary embolism remains a vexing clinical problem. Emboli are often unsuspected clinically. Ventilation-perfusion (VQ) scintigraphy is known to miss some emboli found on pulmonary angiography. Some physicians recommend diagnostic approaches in which the lung scan plays a relatively minor role, and angiography is required for many patients. Major prospective studies recently have made available objective data for formulation and evaluation of diagnostic and therapeutic strategies. These data suggest that the lung scan is a better predictor of patient outcome than has been previously appreciated. The goal of V/Q scanning is not detection of pulmonary emboli per se, but rather the identification of patients at a high or low risk for future embolic events if they are not anticoagulated. Several studies have shown that some emboli found on angiography are clinically benign and, in the absence of persistent thrombosis of the lower extremities, do not require anticoagulation. Treatment trials and clinical follow-up studies have shown that although the V/Q scan is not always predictive of angiogram results, it is a reliable predictor of patient outcome. In the absence of deep vein thrombosis, the low-probability scan identifies a patient population not requiring anticoagulation. When combined with objective studies of the venous system, the ventilation-perfusion lung scan provides a guide to management in the great majority of patients. Pulmonary angiography is required only occasionally. PMID- 1754892 TI - Advances in ultrasound imaging of venous thrombosis. AB - In the contemporary clinical setting, a diagnosis of deep vein thrombosis can be established using ultrasound. While different ultrasound modalities, including direct B-mode venous imaging, Doppler, and vein compression, have been employed to diagnose clot, it is the compression technique that has been established as the dominant method. In venographically controlled series, compression ultrasound has demonstrated a 93% sensitivity and 99% specificity for clot detection. These remarkable results have been achieved without the evaluation of calf veins. Recent improvements in instrumentation have permitted the direct visualization of calf veins, and it would seem likely that this will result in even better sensitivity for clot detection. PMID- 1754893 TI - Antifibrin scintigraphy in the diagnostic evaluation of acute deep venous thrombosis. AB - Antifibrin scintigraphy is a new and innovative approach to the diagnosis of acute deep venous thrombosis (DVT). Many antifibrin monoclonal antibodies (Mo Abs) have been described, but only two, 59D8 and T2G1s, have undergone broad preclinical or clinical investigation. Both of these MoAbs recognize an epitope on the amino terminal end of fibrin. The epitope for 59D8 and T2G1s is available for binding only on newly formed, acute thrombi. Preclinical studies have confirmed the specificity of these MoAbs for acute DVT, and have demonstrated their ability to image experimentally induced DVT. Preliminary clinical studies in patients with signs or symptoms of DVT have evaluated indium-111 59D8 Fab and technetium-99m T2G1s Fab'. Fragments of the intact MoAbs are employed to promote faster blood clearance and to reduce immunogenicity. The initial clinical studies indicate that antifibrin scintigraphy has a diagnostic accuracy approaching 90%. Antifibrin scintigraphy has the potential for overcoming many of the deficiencies of both invasive (contrast venography) and noninvasive (Doppler/ultrasound, impedance plethysmography) methods for detecting DVT. With a single procedure, it provides an accurate and rapid evaluation of both lower extremities, both above and below the knee. Because of its unique specificity for acute DVT, it should have excellent potential for use in patients with suspected acute, recurrent DVT, a condition difficult to diagnose by all currently employed tests for DVT. PMID- 1754894 TI - A noninvasive strategy for the management of patients suspected of pulmonary embolism. AB - As a consequence of recent studies that have (1) established the role for ventilation-perfusion lung scanning in the diagnosis of pulmonary embolism, (2) clarified the contribution of clinical assessment to the diagnostic utility of lung scans, and (3) established a role for the noninvasive assessment of the lower extremities for deep venous thrombosis in patients suspected of having pulmonary embolism, we can now manage clinically stable patients suspected of pulmonary embolism without need for invasive diagnostic procedures. The various studies establishing this approach are reviewed, and an algorithm is presented that allows for the noninvasive workup of clinically stable patients suspected of having pulmonary embolism. PMID- 1754895 TI - Etidronate sodium therapy--a cause of poor skeletal radiopharmaceutical uptake. PMID- 1754896 TI - Intense focal uptake of technetium-99m diphosphonate in a soft tissue mass. PMID- 1754897 TI - Panda sign--avid and symmetrical radiogallium accumulation in the lacrimal and parotid glands. PMID- 1754898 TI - [Light adaptation properties of receptor potentials of cyprinid retina]. AB - It was previously reported that changes in sensitivities of electroretinographic b-wave in the course of light adaptation depended on the intensity of background lights. B-wave sensitivity decreased with time by dimmer background lights, while it recovered during illumination with background lights of higher intensities. In this work we examined light adaptation properties of glutamate-isolated receptor potentials (P III components), using isolated and superfused cyprinid retinas. During dimmer background illumination, P III components were unchanged. When background lights were increased above certain levels, P III components showed partial recovery with time in the light. A detailed analysis of spectral sensitivities of P III components and their increment thresholds for several wavelengths indicated that the recovery of P III sensitivity appeared with background lights at which rod function was taken over by cone function. The results suggest that the recovery of b-wave sensitivity during brighter background illumination is partially a reflection of the adaptation property of cone photoreceptors. PMID- 1754899 TI - [Measurement of central motor conduction time (CMCT) in healthy Chinese subjects]. AB - Transcutaneous electrical stimulation of the central nervous system was used to measure CMCT between the human cerebral cortex and spinal cord. 64 normal volunteers (46 healthy adult males and 18 females, age of 20-67 years, body height of 156-185 cm) were recruited as experimental subjects. Action potentials of muscles were recorded from upper limb (Thenar) and lower limb (Muscle tibialis anterior) following cortical and spinal stimulation. The cortical and spinal latent periods (Lcor., Lsp.) were measured and CMCT was obtained by subtracting Lsp. from Lcor. for each muscle. The CMCT between the cerebral cortex and the first thoracic (Th1) cord was 6.69 +/- 1.48 ms, while that between the cerebral cortex and the first lumber (L1) cord was 12.90 +/- 1.59 ms. Statistical analysis indicated that CMCT was not related to sex, age, body height and left or right side of the body as well. The motor conduction velocity in spinal cord (MCVsp) between Th1 and L1, [distance (Th1 to L1)/CMCT (Muscle tibialis anterior)-CMCT (Thenar)] was found to be 71.34 +/- 10.89 m/s, which corresponds to the conduction velocity of the large fibers in the pyramidal tract. The results of the present study are valuable in diagnosis and prognosis of motor system diseases in CNS. PMID- 1754900 TI - [Changes of the arterial baroreflex sensitivity in one-kidney Grollman hypertensive rats]. AB - The objective of this study was to investigate the changes of arterial baroreflex sensitivity (ABS) in one-kidney Grollman hypertensive rats. The blood pressure was altered with phenylephrine or sodium nitroprusside. Mean arterial pressure (MAP) and pulse interval were recorded simultaneously and the MAP-pulse interval regression line was constructed. All rats were divided into three groups: Grollman-operation group, sham-operated group and normal group. ABS was determined at the 3rd week after operation. The results were as follows: The ABS of the Grollman hypertensive group was significantly lower than that of the sham operated group (P less than 0.01). After i.v.c. injection of 150 micrograms captopril the MAP of both groups are lowered, but more significantly in Grollman than in the sham-operated group (P less than 0.05, at 35 min after injection). From 35 to 60 min after injection, the MAP of the sham-operated group has practically reached a steady level while that of the Grollman group still shows significant tendency of decline. At 60th min, the ABS of the hypertensive was significantly increased than that measured 60 min before injection (P less than 0.05), while similar measurements for the sham-operated group showed only a slight or much less significant increase. MAP was increased and ABS was decreased by i.v.c. injection of 8 micrograms angiotension II in the normal group. The results of the present investigation indicate that ABS decreases during the development of one-kidney Grollman hypertensive rats, and that this change appears to be related to the increased concentration of angiotension II in the brain. PMID- 1754901 TI - [Central norepinephrine and angiotensin II contents in the brain regions of spontaneously hypertensive rats (SHR) and the interaction between them]. AB - The norepinephrine (NE) and angiotensin II (A II) contents in the brain regions of SHR and WKY (Wistar Kyoto) rats at different ages were determined by fluorospectrophotometry and radioimmunoassay. The systolic blood pressure (SBP) of the rats was measured indirectly with a tail cuff technique in conscious state. The results were as follows: There was no significant difference in the central A II and NE contents between SHR and WKY rats at 8-week age. Since 12th week age the SBP of SHR has increased gradually, up to 16th to 20th week and then maintained steady level. Whereas there was no significant change of SBP in WKY rats in the same span of age. In the early and late states of hypertension the A II contents in the medulla oblongata, pons, hypothalamus and nucleus caudatus of SHR were markedly higher than those of the age-matched WKY rats. But the change of NE content of SHR in the early stage showed a different picture as compared with that of WKY rats, i.e., NE decreased in medulla oblongata and anterior hypothalamus but increased in pons, posterior hypothalamus and nucleus caudatus. However, in the late stage there was no such significant difference between SHR and WKY rats. Consequently, it is suggested that the central A II and NE participated in the development of hypertension of SHR, and that the maintenance of hypertension is mainly dependent upon the increased A II content. Microinjection of captopril or 6-OHDA in the lateral cerebroventricle of SHR elicited a decrease of BP and reduction of both A II and NE contents in the medulla and hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754902 TI - [Effects of antihypertensive factor from erythrocytes of essential hypertensive subjects on blood pressure in rats]. AB - The effects of antihypertensive factor (AHF) from erythrocytes of essential hypertensive human subjects on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), Wistar-Kyoto rats (WKY) and Wistar rats were examined. Single intraperitoneal injection of AHF (1.6 mg/kg body weight) resulted in a significant decrease in SBP of SHR and RHR. At 10 min postinjection, AHF lowered the SBP in SHR by 34.0 mmHg. SBP recovered to the original level at 3 h. The maximal decrease of SBP in RHR by 92.5 mmHg was at 24h postadministration and the SBP did not recover until the 9th day. When AHF was administered via femoral vein (0.8 mg/kg body weight), the maximal decrease values of the SBP and the DBP were 42.8 and 48.2 mmHg in SHR at 12 min and 38.3 and 42.5 mmHg in RHR at 25 min postinjection respectively. The DBP in Wistar rats decreased considerably (from 96.7 +/- 12.9 to 83.3 +/- 11.7 mmHg) at 5 min postadministration of AHF, but no effect on DBP in WKY rats was observed. The depressor effect of AHF on SBP in RHR was dose-dependent. AHF could also antagonize the pressor effect of norepinephrine in Wistar rats. PMID- 1754903 TI - [Effects of stimulation of arcuate nucleus on intragastric pressure and peripheral pathway analysis in rats]. AB - The effect of electrical stimulation of arcuate nucleus (ARC) on intragastric pressure (IGP) was examined on 68 Wistar rats anaesthetized with urethan. The results were as follows: (1) Stimulation of ARC could induce an obvious decrease of IGP. (2) This effect was not blocked by atropine but partially by vagotomy. (3) Extirpation of celiac neural plexus or intramuscular injection of phentolamine could obviously reduce the suppression of IGP induced by ARC stimulation, but intramuscular injection of propranolol had no such effect. (4) After vagotomy plus extirpation of celiac neural plexus, IGP could still be made a decrease by stimulating ARC. In view of the present investigation, it is suggested that (1) Both sympathetic nerve and vagus are involved in the reduction of IGP induced by ARC stimulation, the former and the latter routes being respectively mediated by alpha-adrenoceptor and non-cholinergic, non-adrenergic fibres. (2) Humoral factors may be also involved in this effect of ARC stimulation. PMID- 1754904 TI - [Effect of zinc on immune function in normal mice]. AB - Swiss mice were used for studying the effects of zinc on the immune function and on the structure of thymus. The experimental results showed that: 1) When mice were administered with a dose of zinc 0.2mg/d of mouse for 15 d, the number of mature T lymphocyte in peripheral blood increased significantly, the transformation of lymphocytes and DTH response were both markedly enhanced; phagocytosis of peritoneal macrophage was suppressed, but the production of IgM and the weight of thymus were not affected. 2) The shape of lymphocyte nucleus of the thymus cortex became irregular by administration of zinc. So, a certain immunity promotive dose of zinc may impose a latent injury to the lymphocyte of thymus. PMID- 1754905 TI - [Effect of salt-loading on prostacyclin and thromboxane metabolism in kidney]. AB - For evaluating the role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the metabolism of salt and water, the metabolic products of PGI2 and TXA2 (6-keto PGF1 alpha and TXB2 respectively) were measured by radioimmunoassay in salt loaded rabbits. 36 normal rabbits were randomly divided into 3 groups: 1. normal control group; 2. 3h salt-loading group (3 h group); 3. 24 h salt-loading group (24 h group). Both the 3 h and 24 h groups were given 0.9% NaCl solution by subcutaneous injection to the hind legs. The kidneys were dissected into 4 slices: outer cortex, inner cortex, outer medulla and inner medulla. The plasma 6 keto-PGF1 alpha in the 3 h group was increased from the control value of 46.61 +/ 19.04 pg/ml to 111.63 +/- 58.36 pg/ml (P less than 0.01). All of the dissected renal slices also showed significant increase of 6-keto-PGF1 alpha synthesis in both the 3 h and the 24 h groups (P less than 0.001 vs. normal). The urinary sodium concentrations have a good correlation with 6-keto-PGF1 alpha in plasma or in kidney tissues. Plasma TXB2 in normal group was 499.27 +/- 197.86 pg/ml, but no significant change was found in the 3h group. However, in the 24 h group it decreased significantly to 218.76 +/- 114.54 pg/ml (P less than 0.05 vs. normal group). Although the TXB2 increment was significant only in inner medulla, all other dissected renal slices showed some increase of TXB2 synthesis too. It is concluded that salt-loading can cause increase of PGI1 and TXA2 synthesis in normal renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754906 TI - [Antiinflammatory drugs inhibit the elevation of plasma CGRP concentration in endotoxin shock in rats]. AB - In the present study, we observed the effects of indomethacin, ibuprofen, naloxone and morphine on plasma CGRP concentration 3 h after endotoxin shock in conscious rats. The results showed that indomethacin, ibuprofen and naloxone significantly inhibited the elevation of plasma CGRP concentration as well as reduced the lesion in the intestine during endotoxin shock. However, morphine had no significant effect. The data are consistent with our hypothesis that prostaglandin, as one of the inflammatory mediators which increase in shock may be an important endogenous factor for triggering the CGRP release during endotoxin shock. PMID- 1754907 TI - Hemorrhage associated with "bone crisis" in Gaucher's disease identified by magnetic resonance imaging. AB - Children suffering from Gaucher's disease were examined by magnetic resonance imaging (MRI) during a characteristic episode of "bone crisis". An unexpectedly high intramedullary as well as subperiosteal signal was observed on both the T1- and T2-weighted sequences in 5 patients, suggesting a subacute hemorrhage or hematoma. It is conceivable that such a painful hemorrhage is an important component of the "bone crisis" phenomenon. Furthermore, in these cases this is a specific sign which may enable differentiation of bone crises from other types of bone pain associated with Gaucher's disease. PMID- 1754908 TI - Forearm deformities in multiple cartilaginous exostoses. AB - Sixteen patients with 20 forearm deformities were reviewed. The deformities were classified into three types. The degree of ulnar tilt of the radius, ulnar displacement of the carpus, and relative ulnar shortening were determined. The severity of the deformity correlated with these measurements. Metacarpal lengths were also measured. Significant metacarpal shortening without exostoses was seen in 10 of 11 patients and with exostoses remote from the metaphysis in 10 of 13 patients. Metacarpal shortening correlated with the type and severity of deformity. PMID- 1754909 TI - Pulmonary Aspergillus chest wall involvement in chronic granulomatous disease: CT and MRI findings. AB - Pulmonary Aspergillus infection in patients with chronic granulomatous disease tends to involve the chest wall and consequently carries a high mortality rate. We report the findings of computed tomography (CT) and magnetic resonance imaging (MRI) in three such cases. One patient underwent both CT and MRI, one, CT only, and one, MRI only. In all three, both CT and MRI demonstrated pulmonary consolidations with direct extension to the adjacent chest wall. In both patients who were examined by CT, scans revealed permeative osteolytic changes of adjacent rib or spine compatible with osteomyelitis. In both patients who were examined by MRI, adjacent chest wall involvement was depicted on T1-weighted images and showed increased signal intensity on T2-weighted images. In one of these patients, the chest wall lesion was well defined on T2-weighted images, an appearance compatible with abscess. Epidural extension was demonstrated on MRI in the other patient, who later developed paraparesis. We suggest that CT and MRI have a complementary role in evaluating chest wall invasion by pulmonary Aspergillus infection in chronic granulomatous disease. PMID- 1754910 TI - Osteoarthritis associated with distal interphalangeal joint involvement in rheumatoid arthritis. AB - A study was undertaken to investigate the relationship between the clinical and radiological findings in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and combined osteoarthritis and rheumatoid arthritis (OA/RA) affecting the hands. Fifty patients were selected for each group from those attending a rheumatology clinic. The study showed a good correlation between the clinical and radiological diagnosis of combined OA/RA and that marginal erosive changes in the distal interphalangeal (DIP) joints occur more commonly in patients with rheumatoid arthritis who have coexisting osteoarthritis. PMID- 1754911 TI - Magnetic resonance imaging features of fractures using the short tau inversion recovery (STIR) sequence: correlation with radiographic findings. AB - The MRI characteristics of fractures have been described on the basis of spin echo (SE) images emphasizing T1 and T2 contrast. These previous studies were carried out for injuries in which radiographic proof was often lacking. In comparison with SE images, short tau inversion recovery (STIR) images have been shown to provide superior contrast between normal and abnormal marrow. To determine the MRI characteristics of fracture using STIR pulse sequences, we reviewed 28 patients who had radiographic evidence of fracture and were examined with T1-weighted SE and STIR sequences. MRI marrow signal abnormalities were demonstrated at all fracture sites ranging in age from less than 24 h to 8 weeks. The extent of marrow signal abnormalities exceeded the size of corresponding radiographic findings of fracture in all cases. The MRI features of fractures on T1-weighted SE images consisted of irregular intramedullary zones of hypointensity. On STIR images a corresponding zone of hyperintensity extended to the outer cortical margin. Intramedullary lines of hypointensity extending to the inner cortical margin were identified within the hyperintense marrow abnormality on STIR images in 64% of the fractures. The results of this study show that MRI using T1-weighted SE and STIR sequences can consistently demonstrate prominent signal abnormalities at fracture sites including those in which radiographic signs are subtle. PMID- 1754912 TI - Skeletal manifestations of granulocytic sarcoma (chloroma). AB - Skeletal manifestations of chloroma were reviewed in five patients. In four cases, a chloroma was the initial manifestation of a systemic disease. In the fifth, an elderly patient developed a bone lesion during a blastic crisis while under treatment for chronic myelogenous leukemia. Two patients presented with lytic lesions of the ribs, two with lytic lesions of the femur, and one with a predominantly sclerotic lesion of the scapula. The laboratory findings in two patients were within normal limits. All lesions were confirmed by bone biopsy. PMID- 1754913 TI - Bursitis in association with solitary osteochondromas presenting as mass lesions. AB - Three patients with solitary osteochondromas which were increasing in size have been recently examined. Plain films were available on all patients; two patients had MR studies, and two had CT scans. In all three cases, malignant transformation of the osteochondroma was suspected from the cross-sectional imaging studies, but pathologic examination proved that these patients all had bursa formation without any evidence of malignancy. The incidence of this rare complication of solitary osteochondroma is discussed. Ultrasound is also recommended for the evaluation of enlarging solitary osteochondromas. PMID- 1754914 TI - Seronegative arthritides of the anterior chest wall: a follow-up study. AB - Fourteen patients with arthritis of the anterior chest wall (ACW) as part of ankylosing spondylitis, reactive arthritis, and arthritis associated with psoriasis and/or pustulosis palmoplantaris (PPP) were re-examined after periods of 5-15 years (mean 9 years) using tomography. The findings were compared with those of 24 similarly examined patients with predominant osseous sclerotic ACW lesions or monarthritis of the manubriosternal joint. Pronounced osseous hyperostosis in the region of the sternoclavicular joint accompanied by ossification of the costoclavicular ligament was found to occur only in patients with PPP lesions. Patients with ankylosing spondylitis and reactive arthritis developed slight or moderate hyperostosis only and no ligament ossification. Predominant osseous sclerotic sternal and clavicular lesions occurred in patients with PPP and in patients without skin disease or traits suggesting well-known arthritides, but not as part of ankylosing spondylitis and reactive arthritis. Arthritis of the manubriosternal joint and upper sternocostal joints developed in all forms of arthritis. PMID- 1754915 TI - Case report 676: Malignant granular cell tumor (schwannoma, myoblastoma), disseminated. AB - A rare case of metastatic, lethal, malignant granular cell tumor is presented in a 77-year-old woman. Metastases involved numerous sites, including the skeleton. The key clinical and pathological findings and differential diagnosis in benign and malignant granular cell tumor were discussed, including a review from the English literature of 23 cases of malignant granular cell tumor. The differential diagnosis was considered in detail. PMID- 1754916 TI - Case report 693: Schneckenbecken dysplasia. AB - Three siblings with SBD from consangineous parents are reported. The prenatal diagnosis of a short-limbed form of dwarfism was made by ultrasonography and the final diagnosis in the index case by radiography, demonstrating a short-limbed, platyspondylic dwarf with a snail-like configuration of the ilium and vertebral bodies, flat on AP and round on lateral view. The histological examination showed a generalized, severe disturbance of cartilage formation with marked hypercellularity of proliferating and resting zones, reduction of intercellular matrix, and shortening of the irregular columns of proliferating cartilage. The ultramicroscopic findings were nonspecific. This is the first report of SBD after the original description, bringing the total to 14 cases in 5 families. The correct radiological diagnosis and the differential diagnosis, in particular thanatophoric dysplasia, are essential for genetic counselling and obstetrical guidance of families affected with this autosomal recessive dysplasia. PMID- 1754917 TI - Case report 694: Cervical paravertebral circumscribed myositis ossificans. AB - MO is a soft-tissue mass, reported only 3 times in the cervical paravertebral area in a search of the literature. We describe an additional case in a 10-year old girl. We emphasize that in the unusual radial radiopaque roentgenographic image, a malignant tumor could be considered. We also stress that CT scanning can be of great value in establishing the diagnosis. The clinical types and the radiological and pathological features of MO are described in some detail and the "zonal" sign is described. PMID- 1754918 TI - Case report 695: Cementifying fibroma of the proximal end of the tibia. AB - A case of a cementifying fibroma in the proximal end of the tibia in a 31-year old woman is presented. The lesion was expanding but well-defined with amorphous central calcification. The unique, calcified, cementum-like particles in a fibrous stroma have been reported in only four previous cases in long bones. The histological and radiographic differences between a cementifying fibroma, bone cysts with cementum, and a true cementoma are discussed. The radiological differential diagnosis of fibrous dysplasia, giant cell tumor, and low grade central osteosarcoma was considered. PMID- 1754919 TI - Case report 696: Chondroblastoma of the right acetabulum and superior pubic ramus. AB - A case of chondroblastoma involving the right acetabulum and superior pubic ramus in a 60-year-old man has been presented. Tissue was obtained by open biopsy. The clinical and radiographic characteristics of chondroblastoma in general, and this tumor in particular, were discussed. The histopathology and differential diagnosis were also considered. The relatively uncommon site of the tumor and its occurrence in an older patient made the radiographic diagnosis difficult, and other possibilities were discussed. PMID- 1754920 TI - Case report 697: Neuropathic arthropathy of the shoulder with no identified cause. AB - Two cases of neuropathic disease of the shoulder without evidence of a neurological disorder are described. The absence of any neurological disorder led to the cases being initially mistaken for primary neoplasms of bone, lending support to the vascular theory of pathogenesis of this lesion. Careful attention to the radiographic features and knowledge that a neurological disorder need not be present should lead to the correct diagnosis. PMID- 1754921 TI - Case report 698: Osteoma of the clavicle. AB - We have presented a case of an osteoma of the clavicle in a 41-year-old man. The possibility of alternate diagnoses--in particular, ancient osteochondroma, posttraumatic hyperostosis, and parosteal osteosarcoma--was addressed. However, the pathological examination was most consistent with the diagnosis of osteoma. This benign bone lesion is most often found in the calvarium, jaw, and face. Osteomas of long bones remain extremely rare, except in the setting of Gardner's syndrome. PMID- 1754922 TI - Toward a redefinition and contextualization of the abortion issue. PMID- 1754923 TI - Confronting the lack of resources for patients with AIDS dementia complex. PMID- 1754924 TI - Reviving the action research model: combining case and cause with dislocated workers. AB - Action research, a model combining research with activist goals and microlevel and macrolevel social work practice, has received little recent attention in the social work literature. This article reports on an action research project conducted by a major labor union and a university department of social work to assist dislocated workers in New England. A partnership of union-trained peer counselors and social work faculty and students combined a research study with providing direct service to displaced workers, assisting in an organizing project, and developing a policy agenda to assist low-income workers. The author suggests that an action research model can be used by social workers in a wide variety of settings and under different practice auspices. PMID- 1754925 TI - The mediator role in social work practice. AB - The frameworks and skills of a mediator are indigenous to social workers. Mediation's purpose and place in human problem solving are inherent in the definition of social work practice. Decisions about assuming the mediator role with clients require that social workers weigh desired outcomes and constraints of the role. Helping client systems assume power and efficacy to negotiate problem resolution is a needed empowerment-oriented strategy in social work practice. Teaching client systems to negotiate and mediate for themselves may result in mutually agreeable solutions and growth and attitude change on the part of the client. PMID- 1754926 TI - A role perception study of school social work practice. AB - A study conducted in an intermediary educational agency examined principals' and special education teachers' perceptions of actual and ideal performance of school social work tasks. Those services seen as provided most frequently are directed toward individuals. Although respondents want these services to continue, they also want more group work services. The study contained several recommendations, including one for the development of individualized building service plans and another on the development of a screening process for special education assessments. PMID- 1754927 TI - Changing the focus of social work supervision: effects on client satisfaction and generalized contentment. AB - An experiment and three replications were conducted in which the focus of social work supervision was varied to compare client outcomes under two conditions. A social work supervisor gave two male and two female mental health center staff eight weeks of supervision with a mixed focus on administration, training, and clinical consultation. This was followed by eight weeks of client-focused supervision in which questions were asked about client problems and staff interventions in the context of client outcomes. The dependent variables were mean weekly caseload reports of generalized contentment and three dimensions of client satisfaction. Outcome data were plotted and examined with visual analysis for trend and aggregated for effect-size calculations. Adult outpatients reported significantly greater satisfaction under client-focused supervision. The findings suggest that social work supervision affects clients, and that client satisfaction improves if supervisors ask questions about client problems and staff interventions in the context of client outcomes. PMID- 1754928 TI - Practitioner involvement in clinical evaluation. AB - Contrary to popular belief, social workers are evaluating their practice, but what they do falls short of the use of quantitative procedures that researchers have promoted. Data obtained from a survey of social workers drawn from the National Association of Social Workers national membership list suggest that the gap between practitioners and clinical researchers may stem in part from different mindsets as well as from actual differences in the commitment to the importance of clinical evaluation. Moreover, in the minds of practitioners there appears to be a sharp distinction between formal single-subject design studies and the general evaluative tasks in which they routinely engage. PMID- 1754929 TI - A model of case management: toward empirically based practice. AB - Case management is highly valued as an intervention method for providing service to clients requiring long-term care. However, it lacks definitional consensus and conceptual clarity. An explicit, empirically based model of case management is presented on the basis of 15 functions and their dynamic interrelationship along a sequential dimension. A series of studies is described by means of which the model was devised, tested, and refined. PMID- 1754930 TI - The six languages of social work. AB - This article describes the six languages that scientifically minded and practice competent social workers need to be fluent in: the lay language of the client, the abstract language of the theorist, the empirical and often quantitative language of the researcher, the categorical language of the information scientist, the technical terminology or jargon used by helping professionals, and the preferential language that conveys values. It is the thesis of this article that social workers need multilingual and translingual proficiency in moving rapidly back and forth among these languages for maximum effectiveness and humane service. PMID- 1754931 TI - Facilitating progress in group therapy by means of the basic human relations laboratory. PMID- 1754932 TI - Changes in fatigue characteristics of cervical paraspinal muscles with posture. AB - The median frequency of the myoelectric signal of the cervical paraspinal muscles was studied in 28 normal subjects in prone and sitting positions. Median frequency parameters (initial median frequency and slope of the median frequency) of the myoelectric spectrum were monitored during sustained isometric neck extensions at 20%, 50%, 80%, and 100% of maximum voluntary contractions. Force output of 100% maximum voluntary contractions was also measured in the prone and sitting positions. Reliability of the median frequency parameters for repeated trials at various force levels was computed. There were significant differences (P less than 0.05) in the median frequency parameters between the prone and sitting positions, and there was significantly higher 100% maximum voluntary contractions force production in the prone position than in the sitting position (P less than 0.05). There were also high reliability estimates for the median frequency parameters in both test positions. The cervical paraspinal muscles may use different strategies of recruiting motor units during force production in various postures of the neck. It therefore is necessary to standardize the testing procedures before the median frequency parameters can be considered objectively to measure the muscle function in the neck. PMID- 1754933 TI - Anatomic and biomechanical assessment of transarticular screw fixation for atlantoaxial instability. AB - The purpose of this study is to elucidate anatomically the atlantoaxial transarticular screw fixation described by Magerl in 1979 and compare it biomechanically with Gallie wiring. Five human C1-C2 specimens were tested in flexion/extension and rotation intact, then after wiring and screw fixation. Mean screw length was 39 mm, 25 mm in the C2 lamina and 14 mm in the lateral mass. Angular displacement of screwed specimens was significantly less than control or wired groups. Stiffness at 0-0.5 Nm loads was significantly greater for screwed specimens than for wired or controls (101 +/- 49 Nm, 10.3 +/- 9.2 Nm, and 1.96 +/ 0.18 Nm, respectively). All specimens withstood 5 Nm in flexion and extension without failure. Screw fixation provides stability comparable to Gallie wiring and is stiffer at low-range forces and rotational angles. PMID- 1754934 TI - Postoperative spinal epidural empyema. Clinical and computed tomography features. AB - Epidural empyema is a rare complication of elective spinal surgery. Four such cases are described. The clinical features of this postoperative complication were surprisingly vague and misleading. Fever was uncommon. Local inflammatory signs or rapid neurologic deterioration were absent. Computerized tomography proved useful in diagnosis and follow-up. Unlike spontaneous spinal epidural abscess, postoperative spinal epidural empyema had a benign course. Causative bacteria were miscellaneous. Surgical evacuation of the purulent collection and appropriate antibiotic therapy resulted in cure in all cases. PMID- 1754935 TI - Selection of lumbar fusion levels in adult idiopathic scoliosis patients. AB - Fifty-three adult idiopathic scoliosis patients whose fusions ended caudally between L2 and S1 were reviewed relative to criteria for selection of the lowest fused vertebra and their outcome. The Harrington stable zone, central sacral line, and the presence of rotary subluxation, arthritis, spondylolisthesis, vertebral body and disc space wedging were studied. Preoperative and postoperative pain, quality of life, and decisions for surgery were surveyed with a 94% response. Results showed the older the patient, the lower the fusion. The Harrington stable zone was useful, whereas the central sacral line frequently indicated longer fusions by as much as three segments. The presence of pathoanatomic features also dictated lower fusions. Patients in whom the lowest level of fusion was consistent with selection criteria had reduced frequency and intensity of low-back pain. PMID- 1754936 TI - The Cotrel-Dubousset system--results in spinal reconstruction. Early experience in 47 patients. AB - Forty-seven patients were treated with spinal fusion and Cotrel-Dubousset instrumentation and were followed for an average of 28 months. Spinal procedures included: 1) posterior spinal fusion for idiopathic scoliosis (26 patients); 2) posterior pseudarthrosis repair (5 patients); 3) combined anterior/posterior fusion to the sacrum (6 patients); and 4) combined anterior/posterior osteotomies (10 patients). Group 1: Partial derotational correction was achieved for adolescent idiopathic scoliosis. Group 2: Successful pseudarthrosis repair was achieved in four patients. Group 3: A solid arthrodesis was obtained in two patients, whereas the other three patients underwent revision of sacral screw fixation for pseudarthrosis. One patient died postoperatively. Group 4: Pain relief and a balanced correction was achieved in all patients. The Cotrel Dubousset system appears to be a versatile system and provides a wide range of possibilities for a variety of spinal problems. PMID- 1754937 TI - Common diagnostic and therapeutic procedures of the lumbosacral spine. The North American Spine Society's Ad Hoc Committee on Diagnostic and Therapeutic Procedures. PMID- 1754938 TI - Functional biomechanics of the spine. AB - The exact nature of the mechanisms at work during movement of the human spine are not well understood, nor well defined. The spine supports the torso against loads and allows freedom of motion, within physiologic limits, at the same time. A great deal of information characterizing various attributes of the spine is available. Research has provided values for flexural stiffness, axial compliance, range of motion under various loading modalities, and considerably more. This study will focus not on isolated topics, but rather serve as a broad introduction to the behavior of the spine as a whole. PMID- 1754939 TI - In vitro spinal biomechanics. Experimental methods and apparatus. AB - The functional units making up the spinal column allow fully six degrees of freedom, but with range of motion constraints due to the associated ligamentous and bony structures. Research into the behavior of the spine requires complex testing methodologies, consequently. Reproducing physiologic behavior in the spine requires the application of suitable forces or displacements through loading frames that do not interfere with the its intrinsic behavior. Monitoring of the outcomes can be done on the basis of force, length or pressure measurements, or combinations thereof. An exploration of testing methodologies and apparatus is presented. The applicability and related overheads, due to data acquisition or analysis, of such methods are discussed. This will provide a means for the researcher to assess the hardware requirements to attain the objectives of their project. PMID- 1754940 TI - The use of mathematical models for studies of scoliosis biomechanics. AB - The use of mathematical and other types of models for the study of the biomechanics of scoliosis is reviewed in this article. The article is based on a talk presented at the 1987 Meeting of the Scoliosis Research Society. PMID- 1754941 TI - Biomechanical testing and scoliosis. In vivo methods. AB - Patients with scoliosis deformity can be evaluated from a biomechanical viewpoint by measurement of spinal morphology, back surface topography, and changes in these measurements both acutely and over time. In addition, the forces acting on the spine can be estimated in vivo. Many ethical and practical challenges have been overcome, and these measurement techniques have provided information on spinal deformity and its treatment. Further insights have come from biomechanical analyses of these measurements, and complementary modeling studies. This study reviews the available methodologies and the progress that has been made toward using these methods in assessing outcomes in treatment. Possible future directions for in vivo measurements are suggested for studies of etiology, growth regulation, progression of deformity, three-dimensional assessment of treatment outcome, and monitoring of individual patients. PMID- 1754942 TI - Biomechanics of posterior lumbar fixation. Analysis of testing methodologies. AB - A variety of biomechanical methods have been used for the experimental evaluation of spine instrumentation in vitro. Consensus has not been reached for criteria to compare the performance of dissimilar devices. The range of load-displacement conditions currently used for in vitro testing of spine instrumentation was reviewed, and compared to calculated estimates for flexion, lateral bending, and torsion loads. It is recommended that future studies simulate combinations of loads or displacements associated with common patterns of motion, and that the distraction across the region of injury be measured. For cyclic testing, input frequencies of 4-5 cycles/sec are within physiologic range, and offer advantages over tests at lower frequencies. The development of consistent protocols based on physiologic conditions should facilitate the biomechanical assessment of techniques for stabilizing the human spine. PMID- 1754943 TI - Pitfalls of biomechanical testing. AB - A review of the pitfalls of biomechanical testing and its experimental designs are presented in order to provide a format for the young spinal experimentor, and an outline of procedural error and logical thinking for nonclinical spinal experimentation, be it in vitro, in vivo, or with mathematical modeling. Subsequent sections deal with the specifics of in vitro and in vivo testing and mathematical modeling. PMID- 1754944 TI - Computed tomography and magnetic resonance imaging findings of pigmented villonodular synovitis of the spine. PMID- 1754945 TI - Esophageal erosion. A complication of acrylic fixation in anterior cervical fusion. PMID- 1754946 TI - A congenital defect resembling the Hangman's fracture. PMID- 1754947 TI - Spinal rehabilitation by work tolerance based on objective physical capacity assessment of dysfunction. PMID- 1754948 TI - Social Security Bulletin. Annual statistical supplement, 1991. PMID- 1754949 TI - The osteopathic cranial concept: fact or fiction? PMID- 1754950 TI - The functional relationship between the occlusal plane and the plantar arches. An EMG study. AB - We studied many postural tests with an electromyographical methodology on a group of young men who had a right molar precontact. We compared the results of these tests before and after changing the right plantar arch by placing some plastic on the medial right margin of the homolateral plantar arch (talipes valgus) or on the whole plantar arch (flat foot). We demonstrated the dependence of the occlusal plane on the morphological variations of the plantar arch. PMID- 1754951 TI - The superior laryngeal nerve loop and its surgical implications. AB - Based upon findings from 60 cadavers (120 sides), the incidence of superior laryngeal nerve loop, connecting the cervical sympathetic chain and the superior laryngeal nerve and its branches, the external and internal laryngeal nerve, was 98.3% (118 out of 120 sides). In most cases the loop connected the sympathetic chain and the external laryngeal nerve. The external laryngeal nerve was looped, and not linear as traditionally thought. The loop could be divided into three categories, V-shaped, U-shaped and mixed, and subdivided into 5 types and 17 subtypes according to morphological variation. The loop without exception innervated not only the cricothyroid muscle, but also the thyroid gland. The loop is one of the origins of the thyroid nerve. It seems that for thyroid surgery the loop, when lower in position, should be carefully separated from the superior thyroid vessels before the latter are ligated, in order to preserve a normal nerve supply to the muscle as well as to the part of the gland that remains after surgery. PMID- 1754952 TI - Reliability of the acetabular teardrop as a landmark. AB - This study investigated the effect of tilt and observer reliability on radiographic measurements of the position of a prosthetic acetabular cup in seven dry bone pelves using the teardrop as a landmark. Coronal or sagittal tilt of more than five degrees was easily recognisable and there was effectively no observer variation in the measurements up to this limit. In addition, 90 out of 100 randomly selected antero-posterior pelvic radiographs from an outpatient department were not significantly rotated and 93 demonstrated a clearly defined teardrop. Measurements about the teardrop on routine radiographs are therefore sufficiently accurate to allow assessment of prosthetic position. PMID- 1754954 TI - A new cephalic reference plane for use with magnetic resonance imaging: the chiasmato-commissural plane. AB - A cephalic reference plane is described through the chiasmatic notch and the posterior commissure, which is easily identified on mid-sagittal cuts using magnetic resonance imaging. The horizontal cuts so obtained are almost parallel to the lateral fissure and are perpendicular to the axis of the brain stem. PMID- 1754953 TI - The portal bifurcation and the termination of the hepatic veins: an anatomical investigation into the projection of the ultrasonographically important hepatic vessels onto the anterior body wall. AB - An investigation was carried out on 50 cadavers, in which the projection onto the anterior abdominal wall of the following vascular points was examined: the portal bifurcation, the direction of the course of the right and left branches of the portal vein and the terminal course of the hepatic veins near their entry into the inferior vena cava (IVC). The results are related to a transverse axis passing through the apex of the xiphoid process and the median plane in the supine position. The average position of the portal bifurcation is projected onto a point between a vertical line passing through the midpoint of the right hemithoracic width and a horizontal line passing through a point on the midclavicular line (MCL) corresponding to 57% of the height of the liver measured upwards from its inferior margin. The axis of the prehepatic course of the portal vein makes an angle of about 50 degrees, open downwards, with a vertical line drawn through the apex of the internal angle of the portal bifurcation. A line parallel to the course of the right and left branches of the portal vein is projected on to a surface line cranial to the right costochondral margin, which runs upwards at an angle of approximately 20 degrees towards the apex of the xiphoid process. The termination of the three great hepatic veins is projected at about the level of the xiphisternal joint, one sternal width to the right of the midline. Close to the IVC, the right hepatic vein runs upwards and medially at an angle of between 20 degrees and 30 degrees with the transverse plane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754955 TI - The cystohepatic ducts: surgical implications. AB - The cystohepatic ducts (CHDs) drain the entirety of a hepatic territory of variable extent into the cystic duct or gallbladder (cholecystohepatic ducts). Certain very rare patterns of the CHDs constitute anomalies but as a rule a CHD represents one of the numerous variants of division of the extrahepatic bile ducts. Their existence is explained by the normal anatomic development of the bile-ducts. They are usually discovered during peroperative cholangiography performed during cholecystectomy for gallstones. Their actual incidence is small: 1-2% of cases. A CHD was found by the authors on 12 occasions in a total of 1410 cholecystectomies (0.9%). The CHDs are always bile ducts of the right lobe of the liver and may drain a subsegment or segment, a sector or, exceptionally, the whole of the right lobe of the liver. Peroperative cholangiography does not always allow distinction of the CHDs from other and equally rare variants of division of the extrahepatic bile-ducts, whose existence carries the same practical implications. The existence of the CHDs is unpredictable. Their position renders them particularly vulnerable during cholecystectomy and the seriousness of an accidental injury of a CHD depends on the extent of the hepatic territory it drains. Strict observance of the rules of biliary surgery and routine peroperative cholangiography should preserve the integrity of CHDs draining an extensive hepatic territory. PMID- 1754956 TI - The normal uterus on magnetic resonance imaging and variations associated with the hormonal state. AB - Magnetic Resonance Imaging of the pelvis has lead to a new radioanatomical description of the uterus. Variations in the anatomical zones of the uterus were noted with different sequences used in MRI. There was also structural and signal variation depending on hormonal impregnation. Twenty seven MRIs of pelvices were carried out on 16 female volunteers. Eight of them were on oestroprogesterone as the method of contraception (Group I) and had a single MRI. Six were not taking contraceptives (Group II) and had different MRI's during the same cycle. Two women already had already gone through the menopause (Group III). Results showed differences in the size of the uterus (uterine height, length of the uterine body and cervix, diameter of the cervix) between groups I and II but no cyclic changes were observed within group II. The myometrium was found to be thicker in group I and in the luteal phase of group II females in comparison to the follicular phase in the same group. The endometrial cavity was seen in 40% of cases on T1 weighted sequences; on T2 weighted sequences it was seen in all the cases. It was thicker during the second phase in group II than in group I and III. The myometrial signal compared to that of the bladder content (urine) showed a significant increase between early and late echoes on T2 weighted sequences in group I and during the second phase of the menstrual cycle in group II. No variations, or at times a decrease in signal, were observed during the first phase of the cycle in group II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754958 TI - Abnormal styloid process in a human skull. AB - In a survey of 232 Indian human skulls, unusually long and stout, bilateral styloid processes were found in one of them. The length, thickness, the inter styloid distance and the relations of the styloid processes to other associated structures at the base of the skull are discussed, highlighting the possible importance in clinical and surgical conditions. PMID- 1754957 TI - The lymphatic drainage of the human ovary in vivo investigated by isotopic lymphography before and after the menopause. AB - The authors report 14 lymphoscintigraphies of the ovary, 8 before and 6 after the menopause. Injection of colloid labeled with technetium 99 m with elective lymphatic absorption was made into the mesovarium under laparoscopic control. Frontal and lateral images of the lymphatic drainage were made with a gamma camera 4-6 h after injection. Even in this short preliminary series, the premenopausal women showed major local and regional lymphatic circulation with drainage to the lumbo-aortic and pelvic nodes. After the menopause the lymphatic flow decreased and drainage was essentially by the aorto-lumbar nodes. PMID- 1754959 TI - An anomalous muscle crossing the supraclavicular triangle: the cleidotrachelian muscle. AB - An abnormal muscle is described that passes superficially across omohyoid in the left posterior triangle of the neck. Its origin resembles that of scalenus anterior, but its form is triangular and it inserts directly onto the superior surface of the clavicle just lateral to the clavicular head of sternocleidomastoid. Its anatomical course gives it morphological and embryological interest; its relations in the supraclavicular triangle give it considerable surgical relevance. The name cleidotrachelian muscle is suggested. PMID- 1754960 TI - Lymphatic drainage of the right atrium and ventricle of the heart. PMID- 1754961 TI - Lymphatic drainage of the left atrium and ventricle of the heart. PMID- 1754962 TI - Dorsal arterial supply to the thumb. New surgical possibilities for palmar skin coverage. PMID- 1754963 TI - The peroneus tertius island muscle flap. PMID- 1754964 TI - The subtendons of the abductor pollicis longus muscle. PMID- 1754965 TI - Pain, suffering, and anxiety in animals and humans. AB - We attempt to bring the concepts of pain, suffering, and anxiety into sufficient focus to make them serviceable for empirical investigation. The common-sense view that many animals experience these phenomena is supported by empirical and philosophical arguments. We conclude, first, that pain, suffering, and anxiety are different conceptually and as phenomena, and should not be conflated. Second, suffering can be the result--or perhaps take the form--of a variety of states including pain, anxiety, fear, and boredom. Third, pain and nociception are not equivalent and should be carefully distinguished. Fourth, nociception can explain the behavior of insects and perhaps other invertebrates (except possibly the cephalopods). Fifth, a behavioral inhibition system associated with anxiety in humans seems to be present in mammals and most or all other vertebrates. Based on neurochemical and behavioral evidence, it seems parsimonious to claim that these animals are capable of experiencing anxious states. PMID- 1754966 TI - What is chronic pain? AB - Chronic pain leads to individual suffering and to major costs for all developed countries. Previous studies suggest that both the incidence of disabling chronic pain and the amount of health care consumption due to chronic pain are rapidly increasing. Western medicine is not only often ineffective but may be one of the causes of this epidemic. This article will address the issue of chronic pain of unknown etiology and has the goals of: (1) identifying the factors which have led to our confusion about this topic, and (2) proposing alternative ways of conceptualizing chronic pain and its ensuing behaviors and social consequences. It is concluded that it is essential to discriminate between tissue damage, pain, suffering, pain behaviors, health care consumption, impairment and disability if one is to develop a meaningful conceptualization of the medical, social, economic and political problems of chronic pain. Successful treatment must be defined in behavioral terms such as restoration of normal activities. Disabling chronic pain is often a sign of overwhelming stress engendered by the individual's failure to cope with the demands of industrialized society. PMID- 1754967 TI - Philosophy in epidemiology. PMID- 1754968 TI - [Fatigue, fatigability and weakness--a frequent symptom]. PMID- 1754969 TI - [Cardiovascular causes of abnormal fatigability]. AB - Excess fatigue is a common symptom of many chronic cardiovascular disorders with low cardiac output. Impairment of skeletal muscle function due to metabolic alterations seems to play a major role. In heart failure fatigue is a predominant symptom. It may be an early symptom on diseases with slow but progressive inhibition of blood flow, i.e. in constrictive pericarditis, pulmonary hypertension or mitral valve stenosis. Excess fatigue as a precursor of myocardial infarction is being discussed. Finally fatigue may be a limiting side effect of diuretic and beta-blocking agents. PMID- 1754970 TI - [Pulmonary causes of abnormal fatigability]. AB - Abnormal physical exhaustion and fatigue are often simply regarded as a natural consequence of pulmonary diseases. Apart from factors not specifically related to pulmonary diseases (e.g. consequences of infections or malignant diseases of the lungs), increased work of breathing due to impaired lung/thoracic cage mechanics, the effects of chronic hypoxia and hypercapnia, the consequences of disturbed sleep and psychosocial factors are mainly responsible for the impaired physical fitness and the fatigue in association with lung diseases. A careful case history including psychosocial aspects and a thorough physical examination are essential for an efficient diagnostic evaluation. Tests of pulmonary function not only in the awake patient at rest, but also during sleep or adequate physical exercise can reveal the causes of impaired physical performance and fatigue related to lung diseases. PMID- 1754971 TI - [Endocrine and other medical causes of abnormal fatigability]. AB - Many endocrine diseases can cause fatigue. Tiredness is a frequent symptom of primary and secondary hypothyroidism, hyperthyroidism, excessive glucocorticoid or mineralocorticoid production, primary and secondary adrenal insufficiency, primary and secondary hypogonadism and hyperprolactinemia in the male, acromegaly, diabetes mellitus and diabetes insipidus. A great number of medical diseases other than those mentioned in the articles on cardiological and pneumological fatigue can also cause abnormal tiredness (infectious diseases, hematological, renal, hepatic, gastrointestinal and rheumatological disturbances, vasculitis and malignant tumors). The pathogenesis of tiredness caused by endocrine or medical illnesses, i.e. how the sensation of fatigue is produced, is not clear. The fatigue of the various endocrine or other medical diseases is not disease-specific, i.e. its characteristics do not differentiate it from the fatigue of other illnesses. PMID- 1754972 TI - [Abnormal daytime drowsiness--attempt at typology]. AB - Abnormal drowsiness during the day is defined on the basis of three criteria: 1. subjective feeling of increased tiredness, 2. objective observation of attacks of falling asleep, 3. detection of premature falling asleep in the multiple sleep latency test. About 3 to 4% of the population of modern industrial countries complain of this symptom which very quickly leads to inability to work in numerous occupations (driving instructors, lorry drivers, airline pilots). In many cases, the symptoms can be eliminated by effective methods of treatment. Early diagnosis and therapy is hence an important task of physicians. Clinically suitable tools and methods of measurement for appraising the phenomena are at present: 1. the multiple sleep latency test (Richardson et al., 1978), 2. the multiple staying awake test (Mitler et al., 1982), 3. the vigilance test according to Quatember and Maly from the Vienna test system. In neurophysiological terms, an attempt is made to differentiate between: REM drowsiness, non-REM drowsiness, hypofunction of the arousal systems of the reticular formation, and hyperfunction and overstimulation of the arousal systems of the reticular formation (over-aroused tiredness). Approaches to a clinical typology of abnormal drowsiness are available from two points of departure: 1. Forms of permanent somnolence which are not alleviated but intensified by a brief restorative sleep and resemble the 'oversleeping syndrome' of the healthy individual. 2. Attacks of imperative falling asleep in narcoleptic patients. The characteristic of this form of abnormal drowsiness during the day is that in the interval between the attacks of falling asleep patients can take on any healthy person with regard to alertness, reaction capacity and ready wit. After a brief restorative sleep of less than 5 min., they immediately feel fresh, alert and fit again. PMID- 1754973 TI - [Intense fatigue in humans. Psychosocial and cultural aspects]. AB - A differentiation between the normal sensation of tiredness and the symptom "fatigue" is often difficult. Both are influenced by cultural, social, psychological and biological factors, which can lead--interactively--to symptom formation. Psychiatric disorders frequently associated with fatigue are all forms of depression, somatization and anxiety disorders, chronic pain states and drug abuse among many others. In at least 2/3 of patients with the fashionable chronic fatigue syndrome--formerly called neurasthenia--a psychiatric diagnosis can be made, most of them also suffer from many symptoms attributes to the autonomous nervous system. The clinical approach should be cautious avoiding diagnostic and therapeutic overaction and therapy should emerge from a diagnosis properly assessed. PMID- 1754974 TI - [From the symptom fatigue to an etiological diagnosis--an attempt at differential diagnosis]. AB - One out of three patients seeking the doctors advice complain about fatigue. Two out of three are fatigued because of psychological reasons. A systematic way of analysis of this symptom is described, as well as the characteristics of somatic fatigue syndromes as opposed to psychogenic ones. Finally a brief description is given of the main diseases accompanied by fatigue. PMID- 1754975 TI - [Pharmacovigilance of hypolipidemic drugs (fibrates and probucol), from databanks of the French System of Pharmacovigilance]. AB - The methodology of a retrospective study of the side-effects of the most prescribed lipid lowering drugs, essentially fibrates, is described. This study concerns the last 5-years reports to the French System of Pharmacovigilance, centralized in the common data-base located in Lyon. During this period 36,875 reports were recorded, only 409 in which an hypolipidemic drug is stated as "suspect" (according to WHO's definitions) were selected and analyzed. All fibrates were involved, those most frequently implicated being the most widely prescribed (e.g. fenofibrate represents half of the reports). PMID- 1754976 TI - [Muscular involvement and fibrates. Analysis of databanks of the French System of Pharmacovigilance]. AB - A retrospective study of the muscular adverse reactions of fibrates has been conducted from the last 5-years reports of the 30 French Regional Centers of Pharmacovigilance, centralized in the common data bank located in Lyon. Fifty four reports in which at least one fibrate stated as suspect (according to the WHO's definitions) have been reviewed. Those 54 reports represent 13% of the side effects reported with fibrates during this same period. Fibrates seem to be involved as frequently as prescribed, so fenofibrate was the most frequently suspected and the most prescribed. The most usual terms found were "myalgia" and "elevation of CPK". This study shows evidence of the interest of the data-bank of the French System of Pharmacovigilance (which has collected 36,890 reports with all the drugs during the same period); harmonization in the choice of the terms selected for computerizing the cases would improve the exploitation of this sum of data. PMID- 1754977 TI - [Side effects of fibrates (except liver and muscle)]. AB - If the iatrogenic acute muscular syndromes (rhabdomyolysis) and hepatic diseases following hypolipidemic drugs therapy are very well known, the other unwanted effects associated with fibrate therapy are not well established. It is the reason why we have selected, in the computerised data base of side effects from the French Network of "Centres de Pharmacovigilance" organisation, the pathological events associated with fibrate therapy during five years (1985 to 1989) (with exception for the acute muscular and hepatic diseases). The 277 side effects represent 67% of the side effects in which the product is regarded as "suspect" (S). These effects were observed in 132 men (mean age = 57 years) and 145 women (mean age = 61 years). The most frequently encountered products are: fenofibrate (Lipanthyl) for 30%; ciprofibrate (Lipanor); gemfibrozil (Lipur); bezafibrate (Befizal); each for about 10%. The mean doses used were the same that suggested in the french therapeutic dictionary ("Vidal"). The unwanted effects observed were: Skin reactions: 22.8% Blood disturbances (and hemorrhage): 9.8% Gl diseases (pancreatitis), Libido and psychic disturbances, nervous system disorders: about 6% each. All clotting disturbances (5.8%) are interactions with coumarin derivatives. The incidence of serious side effects was low and the recovery very good in 80.9% of cases: no death. In conclusion, the toxicity of fibrates (with exception for rhabdomyolysis and hepatic reaction) appears unimportant: the most frequently observed side effects are skin reactions and blood disturbances (interactions) and rarely nervous system, psychic or libido disturbances. The recovery is good, and the general toxicity of all products appear to be of the same order of magnitude. PMID- 1754978 TI - ["Eosinophilia-myalgia" syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases]. AB - By November 17, 1989, the MMWR published the 154 first reports of a syndrome consisting of myalgia and eosinophilia (EMS), occurring with the consumption of L tryptophan containing products (L-TrpCp) and which might represent a new clinical entity. To standardize reporting over the country, the CDC of Atlanta developed the following case definition: 1) a peripheral blood total eosinophil count of more than 1 x 10(9) cells per liter 2) generalized myalgia sufficiently severe to affect a patient's ability to pursue daily activities 3) the exclusion of infections or neoplastic conditions. The FDA then, announced its intention to seek a nationwide recall of all tryptophan containing products, followed by other european countries (UK, Germany, France). In France, a first decree (January 4th 1990) completed by a decree on May 11th confirms this decision for one year. This measure did not concern the medicinal products or some dietary supplements for newborn or young children. Since December 11th, 1989, 24 cases have been reported to the Regional Adverse Drug Reaction Monitoring Centres in France. These cases share the same features as the cases notified previously in the USA: overrepresentation of females, no relationship with the time and the daily intake, clinical similarities to the Shulman syndrome, and unknown prognosis. Now, more than one year after the onset of this illness, it seems that discontinuation of the ingestion of L-TrpCp can resolve or improve the symptoms in most cases, but sometimes the syndrome can persist. The causal relationship between the ingestion of L-TrpCp and this syndrome has been established. Whatever the mechanism for the development of EMS among tryptophan users remains unclear, as well as the role of eosinophilia and the factors for fibroblast proliferation. The epidemic emergence of this syndrome in July 89 raises the possibility of the contamination of tryptophan during the manufacturing process. To confirm this hypothesis, the same unusual peak in HPLC analysis was found both in case associated L-Trp lots and in implicated-japanese manufacturer L-Trp lots in USA. But this would not explain the previous EMS reports before this contamination. Other hypotheses consist an inabnormality of tryptophan metabolism and/or an autoimmune process. PMID- 1754979 TI - [Agranulocytosis under metapramine. A "well-known" effect without bibliographical data]. AB - Metapramine (Timaxel) is a tricyclic antidepressant drug devoid of anticholinergic properties. As other psychotropic drugs, it may induce hyperthermia and several case-reports have been published. Agranulocytosis is an exceptional side-effect of this drug. Even if several cases have been reported to Pharmacovigilance structures in France, as far as we know there is no publication of this unwanted effect. The authors reported the case of an old woman who has presented two episodes of fever and asthenia. Blood formula was both times characterized by agranulocytosis without anemia nor thrombocytopenia. The accidental rechallenge of metapramine permitted to conclude to a causal relationship between these hematological events and metapramine intake. PMID- 1754980 TI - [Prospective OMEGA survey (Drug use-pregnancy relationship survey at the French Riviera)]. AB - The survey of drugs used during pregnancy is necessary and the need for prospective studies is recognized. Health book distribution where drug intake is written since the beginning of the pregnancy allows a narrow therapeutic survey. The 350 first books analysis show that pregnant women use an average of well resorbed 1.8 drugs during 1rst and 3rd pregnancy trimesters. The most commonly used drugs are vitamins and iron (by 56% of women), non-narcotic analgesics (40%), antibiotics (40%), veinotonics (38%) and hormonal treatments (25%). PMID- 1754981 TI - [Secondary effects of drugs. The 1979 Halcion experience in the Netherlands, a false alarm?]. AB - In the course of 1979 the Netherlands Centre for Monitoring of Adverse Reactions to Drugs (NARD) received a remarkably large number of reports on patients with unusual and complex psychic disturbances, attributed to the use of the then recently marketed hypnotic triazolam. The interpretation of the data was difficult, however, and several questions could at that time not be properly answered. In the past 10 years a specific benzodiazepine withdrawal syndrome has been identified, showing many similarities with the disturbances as reported in association with triazolam. In addition similar adverse experiences with triazolam have been reported in many other countries. Tablets containing 1 mg and 0.5 mg triazolam, as were widely used in the Netherlands, have in the mean time been globally removed from the market. It is concluded that the triazolam syndrome may be explained as a combination of strong benzodiazepine effects and withdrawal phenomena. The ultra short half-life of triazolam and the high doses used may have contributed to the problems as observed in the Netherlands. The signal perceived by the NARD appears to have been a valuable warning, rightly casting doubt on the safety of triazolam and the original dosage recommendations. PMID- 1754982 TI - [Drug utilization at the end of pregnancy]. AB - To evaluate drug utilization during the last 15 days of pregnancy, one hundred six women were interviewed post-delivery in the CHU Bretonneau in Tours. Eighty three percent received at least one drug during the 15 days preceding delivery and 27% more than 3 different drugs. Treatments for venous disorders (31% of patients), iron (31%), analgesics (25%), antacids (11%), magnesium (11%) and laxatives (11%) were most frequently used. In 92% of cases the drug was prescribed. Five women received a drug with potential risk for the neonate. However only one infant developed and adverse effect, possibly due to benzodiazepine (hypotonia). PMID- 1754983 TI - [Peri-rectal infectious cellulitis with septicemia of anal origin. Suppository on trial]. AB - Rectal route with local or general effects, is an interesting possibility of treatment. Easy use and rapid absorption are two major advantages. But this therapeutic modality is not riskless. We report a case of septicemia with peri rectal cellulitis which was generated by two ano-rectal ulcerations after using Trophires suppositories. The infection was favoured by local application of cortisone. Our original observation, with ano-rectal ulcerations and short use of suppository, confirms the idea of short-term treatment stopped in case of unwanted symptom. PMID- 1754984 TI - [Cardio-circulatory arrest with mifepristone sulprostone combination for pregnancy interruption]. PMID- 1754985 TI - [Proposition for a new imputation approach in pharmacovigilance related to the use of topical agents]. PMID- 1754986 TI - [Thrombocytopenia and tubulo-interstitial nephropathy associated with fluindione]. PMID- 1754987 TI - [Bismuth revisited in Helicobacter pylori gastro-duodenal infection]. AB - The various hypothesis for the explantation of reversible bismuth encephalopathy are reviewed and discussed. Today, this side effect appears to be devoid of mystery, due to uncontrolled and inhibited ingestion of bismuth salts which increased the emergence of genetic and physiopathologic risk factors and brought about the cases of neurotoxicity. Bismuth therapy has shown major efficacy in the treatment of gastroduodenal ulcers. Colloidal bismuth subcitrate is as effective as the H2-receptor antagonists in peptic ulcer. In addition, it offers a lower rate of relapse. This therapeutic benefit has been attributed to a cytoprotective and demulcent action. Moreover bismuth acts as an antimicrobial agent, suppressing the organism Helicobacter pylori which occupies a central place in contemporary views on pathophysiology of ulcer disease. Side effects so far reported have been very infrequent mild and transient when the drug is used at low dosage providing blood-bismuth concentration above toxic values. Colloidal bismuth subcitrate complies to the requirements for a modern drug insofar as it is prescribed in period no longer than 6-8 weeks, followed by 8 weeks bismuth free intervals. PMID- 1754988 TI - [Pharmacokinetics of methotrexate and clinical response associated in the medical treatment of ectopic pregnancies]. AB - Methotrexate (MTX) is used in the medical treatment of unruptured ectopic pregnancy. This drug is administered by intramuscular (IM) or intrasaccular (IS) injection under sonographic control. No data are available concerning the pharmacokinetics of MTX in this new indication. This study compares the two administration routes in 12 patients (21 to 37 years) taken as their own control and presenting with ectopic pregnancy (51 +/- 12 days of amenorrhea). Our aim was to compare the pharmacokinetic profile of MTX for each route to facilitate its use in the future. The initial level of hCG was 4.474 +/- 4.184 mIU/ml. Each patient firstly received 1 mg/kg of MTX intrasaccularly under vaginal sonography. The same dose was injected intramuscularly 48 hours later. The pharmacokinetic profiles of MTX after IS and IM administrations were determined after both injections during 48 hours. MTX serum levels were measured by Fluorescence Polarization Immuno Assay. Data were analyzed by model independent methods and compared by a Wilcoxon T test (p 0.01 was considered as significant). All the unruptured ectopic pregnancy were cured and the hCG serum levels were normalized (10 mIU/ml) in 37 +/- 18 days. After IM administration, AUC0-infinity is significantly (p 0.01) increased i.e., 15.1 +/- 4.1 mumol.h/l versus 11.2 +/- 4.8 after IS injection. T1/2 lambda z and MRT remained unchanged whatever the route is i.e., 11.3 +/- 4.9 h and 8.6 +/- 3.9 h (IS) versus 12.1 +/- 5.9 h and 7.3 +/- 1.8 h (IM). The decrement of AUC0-infinity 8 determined after IS injection might be the consequence of the capture of the MTX by the trophoblastic cells (target cells).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1754989 TI - [Chronopharmacokinetics of dexamethasone in young subjects]. AB - Dexamethasone chronopharmacokinetics was studied in six young subjects 20 to 30 years old. The randomized cross-over study consisted of evening (11.00 p.m.) or morning (08.00 a.m.) dose separated by a period of one week. After the evening administration of the drug, only Tmax (1.77 +/- 0.74 a 11.00 p.m. and 0.99 +/- 0.64 a 08.00 a.m.) and Cmax/Tmax were higher than those determined at 08.00 a.m. This difference might be related to a cyclic variation of the absorption phase of dexamethasone. Thus, in our study, the time of administration has only a weak effect on the pharmacokinetics of dexamethasone. PMID- 1754990 TI - [Myoclonic epilepsy induced by levodopa]. PMID- 1754991 TI - [Regression of propylthiouracil-induced dysgeusia after treatment with zinc]. PMID- 1754992 TI - [Thrombocytopenia probably induced by norfloxacin. Apropos of a case]. PMID- 1754993 TI - Cathepsin G can produce a gla-domainless protein C in vitro. AB - Human polymorphonuclear leucocyte cathepsin G was used in vitro to digest human protein C. Anticoagulant assays showed that the proteinase affected a rapid loss in the anticoagulant activity of the zymogen. Calcium ions almost totally protected the anticoagulant activity of protein C against the action of cathepsin G. Polyacrylamide gel electrophoresis, in the presence of SDS (non reducing conditions), indicated that the proteolytic action of cathepsin G lead, to the removal of a peptide of low molecular mass (PC-L'') from protein C with the consequent formation of a product of high molecular mass (PC-P). Electrophoresis in the presence of SDS (reducing conditions) showed that the PC-L'' fragment was removed from the light chain of protein C (PC-L). N-terminal amino acid analysis of the PC-P product and COOH terminal amino acid analysis of PC-L'' product confirmed that cathepsin G had cleaved position Phe40:Trp41 in the light chain. This cleavage was responsible for removal of the gamma-carboxyglutamic acid (gla) containing region of protein C. PMID- 1754994 TI - Could proteolytic enzyme modulate the interaction platelets/vessel wall in presence of ASA at ultra low doses? AB - Acetylsalicylic acid (ASA) is known to act on platelets and vessel walls. At ultra low doses it reverses the inhibitory effects produced by a vascular fragment. Use of papain on normal platelets in vitro led to the appearance of platelet aggregation without collagen induction with a range of 20.25 +/- 28.91%. In the presence of vascular fragments (without ASA), this "spontaneous" aggregation remained but was reduced (13.26 +/- 27.73%). This effect was reversed by ASA treatment (29.41 +/- 24.17%). Reversion of vascular inhibition by ASA was not modified by papain. PMID- 1754995 TI - Platelet glycogen synthase: further characterization and effect of insulin. PMID- 1754996 TI - Prevalence of antiphospholipid antibodies in deep vein thrombosis and their relationship to blood coagulation and fibrinolysis. AB - Elevated levels of antiphospholipid antibodies are associated with an increased risk of thrombosis. To establish the prevalence of these antibodies in deep vein thrombosis (DVT), IgG and IgM antibodies to cardiolipin (aCL) and phosphatidylserine (aPS) were determined by enzyme-linked immunosorbent assay in 118 patients with DVT either during an acute episode (N = 53) or at least 2 months after acute DVT (N = 65). Most patients (76%) had proximal leg DVT and no one had evident autoimmune disorder. aCL and aPS values higher than 4 standard deviations above the mean value of the control group (147 blood donors) were considered increased. Increased IgG aCL were observed in 10% of DVT patients (controls: 5%, not significant), increased IgG aPS in 16% of DVT patients (controls: 5%, p less than 0.005) and both types in 4% of DVT patients (controls: 3%, not significant). In the subgroup of 41 patients with previous idiopathic DVT, prevalence of increased IgG aPS was the highest: 27% (p less than 0.001). Increased antibodies of IgM isotype were observed in 3% (aCL) and 2% (aPS) of all DVT patients (controls: 8% and 4%, respectively, not significant). Elevated IgG aCL or aPS were not associated with significant changes in platelet count, antithrombin III and protein C. However, in patients with increased IgG aPS deficient fibrinolysis due to high plasminogen activator inhibitor activity was observed before and after 20 min upper arm venous occlusion. DVT patients with increased IgG aPS might be exposed to a greater risk of rethrombosis due to deficient fibrinolysis than DVT patients without these antibodies. PMID- 1754997 TI - Effect of diabetes on photochemically induced thrombosis in femoral artery and platelet aggregation in rats. AB - Effect of diabetes on thrombogenesis was examined by using a thrombus model with photochemical reaction in the rat femoral artery. In streptozotocin-induced diabetic rats for 8 weeks, the formation of thrombus following endothelial injury was significantly slower than that in non-diabetic rats. Insulin treatment normalized the abnormality of thrombogenesis. Aggregation in washed platelets from rats with diabetes was enhanced. However, platelet aggregation in whole blood was reduced in diabetic rats, and plasma from diabetic rats attenuated platelet aggregation. These results suggest that plasma factor(s) and/or other blood cells modify the hyperaggregability of platelets per se in vivo in diabetic rats. Treatment with insulin improved the aggregation in whole blood and washed platelets. In conclusion, diabetes induces the prolongation of thrombogenesis in the rat femoral artery. Hypoaggregability of whole blood is likely to be partly involved in the abnormal thrombogenesis. PMID- 1754998 TI - In vitro effects of two novel calcium antagonists (nitrendipine and nisoldipine) on intraplatelet calcium redistribution, platelet aggregation and thromboxane A2 formation. Comparison with diltiazem, nifedipine and verapamil. PMID- 1754999 TI - Antiplatelet effect of the pyrimido-pyrimidinic derivative RA-642. PMID- 1755000 TI - The transient increase of plasma thrombin-antithrombin III (TAT) complex levels in patients with congenital antithrombin III deficiency during antithrombin III administration is due to extraction of thrombin from fibrin. PMID- 1755001 TI - Human alpha- and zeta-thrombin inhibition by recombinant HV1 and HV2K47 hirudins. PMID- 1755002 TI - Plasminogen activator inhibitor activity as a possible indicator of disease activity in rest angina with angiographically insignificant coronary artery stenosis. AB - To assess the role of fibrinolytic system, 19 patients with rest angina and insignificant coronary artery stenosis and 23 controls performed symptom-limited multistage exercise. Vasospasm was angiographically demonstrated in 12 patients. Pre- and peak exercise blood samples from each patient were assayed to determine the fibrinolytic components. The patients displayed significantly increased PAI activity both under the basal conditions (p less than 0.01) and at peak exercise (p less than 0.01) as compared with the controls. However, the values of other fibrinolytic components, such as t-PA antigen, t-PA/PAI-1 complex and free PAI-1 antigen, in the controls and patients were similar. Nineteen patients were divided into two groups according to PAI activity levels under basal conditions. Nine patients displayed high PAI activity (more than the mean + 1 SD of the control value) under the basal conditions. When compared to the remaining 10 patients, the high PAI activity group had both a significantly short time interval from the last attack to the time of getting the blood sample (p less than 0.05), and a worse short-term prognosis (p less than 0.05). Thus, the level of PAI activity under basal conditions reflected the extent of disease activity, suggesting that PAI activity may be a useful clinical indicator of the severity of rest angina in patients without significant coronary stenosis. PMID- 1755003 TI - Anti-Xa clotting activities in different hepatic-triglyceride lipase preparations from post-heparin plasma. AB - Two different preparations of hepatic triglyceride lipase (HTGL) with comparable lipolytic activities, purified from post-heparin human plasma, were assessed for their anti-Xa activities by two clotting and one chromogenic method. Preparation 1, prepared by heparin affinity followed by ion exchange chromatography, did not contain antithrombin III and exhibited no anti-Xa activity in any of the assay systems. Preparation 2, prepared by two consecutive heparin affinity chromatography steps, was active in all three assay systems, and was shown to contain antithrombin III (AT III). Addition of purified AT III to preparation 1 did not result in the anti-factor Xa activity of preparation 2, and monoclonal antibodies to AT III did not antagonize the activity of preparation 2. These results show that the anti-Xa activity of some HTGL preparations is neither due to the lipase itself nor to the content of AT III, but suggest, that it could be due to contamination with another protein, which binds to heparin sepharose columns but is removed during ion exchange chromatography. Most likely the effect is due to the extrinsic pathway inhibitor (EPI), also called lipoprotein associated coagulation inhibitor (LACI), which has recently been shown to be released by heparin. PMID- 1755004 TI - Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. AB - Veno occlusive disease (VOD) is a frequent complication of allogenic bone marrow transplantation (BMT) for which no predictive blood markers are available. 39 patients grafted for severe aplastic anemia (18), and leukemia (21) were prospectively studied. Of the 39 patients, 5 leukemic patients, but no aplastic patients developed VOD. In all the 5 patients with VOD complications we demonstrated a decrease in factor VII and in protein C before the clinical onset of the disease and before any changes in hepatic enzymes were observed. This decrease is the earliest sign of hepatic involvement by the VOD suggesting that the determination of Factor VII and protein C can be used as a prediction test to identify the patients who are at risk of developing VOD after transplantation. In addition, a toxicity of the endothelial cells was suggested by the observed increase in von Willebrand factor and in Serum Angiotensin Converting Enzyme. Signs of endothelial toxicity was more pronounced in leukemic than in aplastic patients. PMID- 1755005 TI - Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two chain urokinase plasminogen activator (tcu-PA) in plasma in vitro. AB - We have studied the effects of PAI-1 on the conversion of scu-PA into tcu-PA in vitro in plasma containing or not a 125I-fibrin clot by determining tcu-PA activity on S2444. Two preparations of PAI-1 have been used, a fraction of medium conditioned with the monkey Vero cells (Vero-Prep), the antiurokinase activity of which is inhibited at 83% by anti PAI-1 IgG, or purified human PAI-1 from HT 1080 fibrosarcoma cells. Scu-PA purified from human kidney cells has been treated with diisopropylfluorophosphate before use. In plasma, conversion of scu-PA into the tc form is accelerated by addition of anti PAI-1 IgG. In plasma containing a clot, generation of tcu-PA, is considerably delayed after addition of the Vero Prep or human PAI-1. Clot lysis is also decreased but to a lesser extent than it would be expected from the level of tcu-PA activity. Addition of anti PAI-1 antibodies shortens the lag phase before tcu-PA appears and moderatly accelerates clot lysis. These results demonstrate the importance of PAI-1 for the stability of scu-PA in plasma in vitro by delaying its conversion into tcu-PA. PMID- 1755006 TI - Human prostacyclin platelet receptors in diabetes mellitus. AB - Conflicting data have been reported about the impaired sensitivity to the inhibitory effect of prostacyclin (PGI2) in platelets from patients with diabetes. In the present paper we investigated binding of and sensitivity to PGI2 of platelets from insulin dependent (IDDM) (n = 9), non insulin dependent (NIDDM) (n = 8) diabetics and two groups of ten healthy subjects of equivalent age in relation to platelet lipidic content. Platelet sensitivity to PGI2 (PGI2 IC50) was found not significantly changed in diabetics as compared to controls; similarly, no significant differences of the number of high affinity receptors for PGI2 in platelets from patients with IDDM and NIDDM were observed. Platelet sensitivity to PGI2 and PGI2 receptors were found to be significantly related to platelet cholesterol content (r = 0.89, p less than 0.001 and r = -0.80, p less than 0.001 respectively). In conclusion platelet PGI2 receptor changes are not detectable in diabetics in good metabolic control, but could take place when platelet lipid composition is altered. PMID- 1755007 TI - Attenuated platelet aggregation in the presence of high concentrations of lactate. PMID- 1755008 TI - The nitric oxide donor SIN-1 is a potent inhibitor of plasminogen activator inhibitor release from stimulated platelets. PMID- 1755009 TI - Electron microscopic studies of quinine induced ultrastructural changes to platelets. PMID- 1755010 TI - A new procedure for the separation of protein Z, prothrombin fragment 1.2 and calreticulin from human plasma. PMID- 1755011 TI - Clinical analysis of STA-SCA bypass for vertebrobasilar occlusive disease. AB - In order to clarify the effectiveness of extracranial- intracranial bypass in cases of vertebro-basilar occlusive disease, we investigated the operative complication, clinical course and follow-up study of 30 cases undergoing superficial temporal artery-superior cerebellar artery (STA-SCA) bypass surgery. Postoperative angiogram showed the patency of the anastomoses in all cases. No serious surgical complications were observed. The outcome on discharge was excellent, with no morbidity and one mortality which was due to cardiac infarction. In the follow-up study, there were four cases with ischemic symptoms, two with transient ischemic attack and two with completed stroke, one of which was a supratentorial infarction due to internal carotid artery occlusion and the other was a small infarction of pons. There were also two deaths due to cardiac infarction and diabetes mellitus. Favorable outcomes were obtained for the remaining cases. The present study suggests that, STA-SCA bypass, can be performed without surgical and systemic complications and used as an effective therapy for vertebrobasilar ischemia. PMID- 1755012 TI - Follicle-like hemicysts reorganized in monolayer culture of rat thyroid cells in the medium supplemented with isologous serum. AB - Monolayer culture of the cells isolated from rat thyroid glands formed a number of large and three-dimensional (about 200-microns diameter) hemicysts in media supplemented with isologous and high-concentration serum. The higher was the concentration of isologous serum, the larger was the hemicysts and the higher was the uptake of 131I of hemicysts. Substitution of heterologous serum, such as calf or fetal calf serum, for the isologous serum failed to form hemicysts. PMID- 1755013 TI - Dynamic movement of hemicysts reconstructed from monolayer cultures of rat thyroid cells in isologous serum. AB - Time-lapse studies using cine-microscopic observation showed that the hemicysts formed in a culture of rat thyroid cells in a high concentration of isologous serum were found to arise by swelling from the monolayer sheet, gradually increase in size, and then rapidly collapse. The hemicyst volume increased linearly. We speculate that each hemicyst epithelium transport a constant volume of liquid into the hemicyst lumen. PMID- 1755014 TI - Changes in brain stem blood flow under various grades of brain stem ischemia. AB - This report describes a study of brain stem blood flow (BBF) change under various grades of brain stem ischemia in a new experimental rat model. The main damage was caused by occlusion of the median and paramedian perforating arteries of the basilar artery. In this model, hyperperfusion was generally observed in cases of mild or moderate ischemia within 1 hr after recirculation and lasted for approximately 1 hr. During hyperperfusion, BBF increased to over 60 ml/100 g brain/min and was significantly greater than basal values (p less than 0.01). The fact that hyperperfusion was unobserved in some cases might be due to the degree of damage to the medulla oblongata. Hypoperfusion or lack of reflow phenomena was also followed by severe ischemia with remarkable hypotension. It is fairly clear from our results that the pattern of postischemic hyperperfusion is responsible for decreased oxygen availability in the brain stem and dysfunction of autoregulation. Acetazolamide reactivity was disturbed and had an inverse response during hyperperfusion. Such phenomena can be explained by paralytically dilated vessels due to ischemia. If BBF falls below a critical level, as we have seen, postischemic hyperperfusion may be induced with dysfunction of autoregulation and inverse acetazolamide reactivity due to vasoparalysis in the brain stem. PMID- 1755015 TI - Probable binary fission in a Reed-Sternberg cell. AB - A Reed-Sternberg cell in binary fission was observed in a case of Hodgkin's disease of nodular sclerosis type. This was thought to possibly represent a primitive eukaryotic manifestation or a retrograde replay of the endosymbiotic evolution of the modern eukaryotes as a part of devolution of malignancy (Okuyama and Mishina 1990). PMID- 1755016 TI - Commentary on 'Assessment of safety/risk of chemicals: inception and evolution of the ADI and dose-response modeling procedures' by Frank C. Lu and Robert L. Sielken Jr. PMID- 1755017 TI - Hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone: interaction with thyroxine binding sites of rat thyroid hormone carriers ex vivo and in vitro. AB - Previous results have indicated that hexachlorobenzene (HCB)-induced hypothyroidism may be caused by its main metabolite pentachlorophenol (PCP), and by tetrachlorohydroquinone (TCHQ), rather than by the parent compound. In the present experiments it was investigated whether hormone displacement from serum carriers could be a factor in the development of this hypothyroidism. In an in vitro competition assay PCP was an effective competitor for the thyroxine (T4) binding sites of serum carriers, whereas HCB was ineffective. Ex vivo experimental results demonstrated occupation of T4-binding sites in sera from PCP exposed animals but not in sera from HCB- or TCHQ-treated animals. Competing ability for T4-binding sites was still present in sera of PCP-exposed animals but was absent in HCB- or TCHQ-exposed animals. The results suggest that thyroid hormone displacement by the major metabolite PCP may play a role in HCB-induced hypothyroidism. PMID- 1755019 TI - Dehydration is the first step in the bioactivation of haloperidol to its pyridinium metabolite. AB - Haloperidol was found to have a similar metabolic pathway to that of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice microsomal preparations. The 1,2,3,6-tetrahydropyridine derivative of haloperidol was detected in NADPH-fortified metabolic incubation mixtures of haloperidol. Incubation of this dehydrated haloperidol produced the pyridinium metabolite. These metabolites were confirmed by comparison with synthesised compounds using HPLC and HPLC-MS. Dehydration of an alcohol to a double bond represents a novel metabolic pathway. This novel metabolic pathway indicates a MPTP-like mechanism for the Parkinsonism observed with haloperidol in clinical use. PMID- 1755018 TI - Effects of sinefungin and 5'-deoxy-5'-S-isobutyl-adenosine on lipopolysaccharide induced proliferation and protein N-methylation of arginyl residues in murine splenic lymphocytes. AB - The effects of sinefungin (SF) and 5'-deoxy-5'-S-isobutyl-adenosine (SIBA) on lymphoproliferation and protein N-methylation of arginyl residues were investigated in splenic lymphocyte culture in vitro. Both SF and SIBA produced a dose-related inhibition of the lymphoproliferative response to lipopolysaccharide (LPS). The time-course of the inhibition indicated that SIBA had a more inhibitory effect than that of SF at short incubation periods, but SF showed more inhibition when the incubation was prolonged. The effects of SF and SIBA on the lymphoproliferative response corresponded with their effects on the protein N methylation of arginyl residues by protein methylase I. PMID- 1755020 TI - Stimulation of natural killer cell activity by murine retroviral infection and cocaine. AB - The effects of cocaine and murine AIDS on natural killer (NK) cell activity in C57BL/6 mice was studied. Cocaine may play a major role in the development and progression to AIDS in the human population. Chronic intraperitoneal injection of cocaine was shown to cause an increase in NK cell activity over those of saline treated animals. Infection with LP-BM5 murine leukemia retrovirus was also shown to increase NK cell activity. NK cell activity was increased in retrovirally infected mice treated with cocaine beyond that of mice treated with cocaine alone. This study indicates an important immunomodulatory effect of cocaine on NK cell activity, especially when combined with the effects caused by retroviral infection. PMID- 1755021 TI - The effects of thiamine and EDTA on biliary and urinary lead excretion in sheep. AB - Relative efficacy of thiamine (B1) and/or calcium disodium ethylinediaminetetraacetate (EDTA) administration on lead (Pb) excretion via bile and urine was studied in Pb-loaded sheep. The sheep were administered B1 s.c., 75 mg/kg body wt., EDTA i.v., 110 mg/kg body wt., and a combination of B1-EDTA at rates as above. Each treatment was followed by 69 h sampling of blood, bile, and urine. Urinary Pb excretion increased following B1-EDTA greater than EDTA greater than B1 administration. Thiamine and B1-EDTA treatments increased biliary Pb excretion. Overall, B1, EDTA and B1-EDTA administration increased Pb excretion via bile and urine by 72%, 595%, and 842% respectively over basal level (mean +/- SE: 20.1 +/- 2.9 micrograms Pb/h). It has been concluded that thiamine enhances elimination of Pb from the body and this feature may be beneficial in chelation therapy. PMID- 1755022 TI - Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat. AB - This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents. PMID- 1755023 TI - Elevated urinary excretion of beta-aminoisobutyric acid and delta-aminolevulinic acid (ALA) and the inhibition of ALA-synthase and ALA-dehydratase activities in both liver and kidney in mice exposed to lead. AB - Urinary excretion of beta-aminoisobutyric acid (ABA) and delta-aminolevulinic acid (ALA) was investigated in mice exposed to lead (500 p.p.m.) in drinking water for 14 days. Concentrations of both urinary ABA and urinary ALA increased significantly in the lead-exposed mice. However, the degree of increasing excretion was higher in urinary ALA (10-fold of the control) than in urinary ABA (2-fold of the control). On the other hand, it was demonstrated that ALA dehydratase in liver and kidney is inhibited by exposure to lead, while ALA synthase in these tissues has no inhibitory effect. PMID- 1755024 TI - The effect of structurally divergent herbicides on mouse liver xenobiotic metabolizing enzymes (P-450-dependent mono-oxygenases, epoxide hydrolases and glutathione S-transferases) and carnitine acetyltransferase. AB - Male mice were treated with structurally diverse herbicides to study their effect on liver xenobiotic-metabolizing enzymes. Chlorfiurecol, trifluralin, alachlor, propham, MCPP and 2,4-DP caused increases in phase I (cytochrome P-450, ethoxycoumarin O-deethylase, and/or aminopyrine N-demethylase) and phase II (microsomal epoxide hydrolase and cytosolic glutathione S-transferase) activities. MCPP and 2,4-DP also increased cytosolic epoxide hydrolase and carnitine acetyltransferase activities suggestive of peroxisome proliferation. Benthiocarb and molinate increased only some phase II enzyme activities. Dicamba, at the dose employed, caused mortality and decreases in some of the enzymes monitored. Most of the herbicides tested induced xenobiotic-metabolizing enzyme activities, the pattern of induction being dependent on herbicide structure. PMID- 1755025 TI - Binding of the strong bacterial mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy 2(5H)-furanone (MX) to bovine serum albumin. AB - Binding of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to bovine serum albumin (BSA) was studied. MX bound mainly reversibly to BSA but, for a minor part, also irreversibly. It was possible to extract the main part of the reversibly bound MX with ethyl acetate and the extractable compound was chromatographically identical to MX. The affinity-binding characteristics of the interaction with albumin were K = 1.6 x 10(7) M-1, n = 3.4. Furthermore, mutagenicity studies indicated that reversibly bound MX remained mutagenic but that irreversibly bound MX was no longer mutagenic in the Ames test. These results suggest that the binding of MX to albumin is an important factor for both the toxicological effects and the toxicokinetics of MX. PMID- 1755026 TI - Transient heat shock in mid-G1-phase of the C6 glioma cell cycle impairs entry into S-phase. AB - Synchronous populations of rat C6 glioma cells have been obtained by a mitotic selection procedure and used to establish the effect of transient temperature elevation on their progression through the cell cycle. A transient 3-h exposure to a 42 degree C heat shock within defined area in the mid-G1-phase of the cell cycle has been demonstrated to impair progression to S-phase. This anti proliferative heat shock effect was not apparent in asynchronous cell populations. A small, but significant, decrease in 3H-thymidine incorporation was observed (approximately 5%) following an 8-h exposure to heat shock. PMID- 1755027 TI - Uncoupling of oxidative phosphorylation in rat liver mitochondria by chloroethanols. AB - Chloroethanols are toxic chemicals used in industry and also formed as a result of the metabolism of several widely used halogenated hydrocarbons. The effect of 2-chloroethanol (CE), 2,2-dichloroethanol (DCE) and 2,2,2-trichloroethanol (TCE) on rat liver mitochondrial respiration was studied. Rat liver mitochondria were isolated in a medium consisting of 250 mM sucrose, 10mM Tris-HCl and 1 mM EDTA (pH 7.4). Mitochondrial respiration was determined with an oxygen electrode at 30 degrees C and the polarographic buffer consisted of 250 mM mannitol, 10 mM KCl, 10 mM K2HPO4, 5 mM MgCl2, 0.2 mM EDTA and 10 mM Tris-HCl (pH 7.4). With succinate as the respiratory substrate and using chloroethanols (150 mM), CE stimulated respiration by 28.2 +/- 6.5% and DCE by 202.7 +/- 8.2% while TCE inhibited mitochondrial respiration (greater than 95%). The effect of change in the concentration of chloroethanols on mitochondrial respiration was also studied. CE showed maximum stimulation at 600 mM (97.6%), DCE at 150 mM (202.6%) and TCE at 30 mM (313.6%). Respiratory stimulation was independent of mitochondrial protein concentration. Chloroethanols (optimal concentrations for respiratory stimulation with succinate) inhibited mitochondrial respiration when glutamate-malate was used as the respiratory substrate. Estimation of adenosine triphosphate (ATP) showed that chloroethanols inhibited the synthesis of ATP. These results indicate that chloroethanols stimulate mitochondrial respiration by uncoupling oxidative phosphorylation and that the uncoupling potency is proportional to the extent of chlorination at the beta-position of haloethanol. PMID- 1755028 TI - Mutagenicity studies of kojic acid. AB - Kojic acid, a fungal metabolite produced by some species of Aspergillus and Penicillium, was found to induce sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of the rat liver S9 mix. Furthermore, this compound was demonstrated to induce mutations in Salmonella typhimurium strains TA98 and TA100 using both plate-incorporation and preincubation methods. PMID- 1755029 TI - Immunochemical and immunohistochemical studies of cadmium associated proteins in Rana tadpoles. AB - Previous observations suggested that Rana tadpoles treated with aqueous cadmium (Cd) accumulate Cd in their liver and mesonephros. In order to study the response to Cd in these tissues we (a) exposed tadpoles in mid-limb bud stages to sublethal quantities of Cd, (b) isolated Cd-associated protein (CAP) from a liver cytosol fraction, (c) prepared a heterologous rabbit antiserum against glutaraldehyde-treated CAP (G-CAP), (d) used the rabbit anti-G-CAP antiserum in order to assess the tissue distribution of CAP in Cd-treated and untreated tadpoles, and (e) assessed species cross-reactivities of our anti-G-CAP with CAPs and metallothioneins (MTs) isolated from Cd-treated vertebrate liver cytosol fractions. We found that (a) CAP was present in higher quantities in liver cytosol obtained from Cd-treated tadpoles compared to liver cytosol obtained from untreated control tadpoles, (b) indirect immunofluorescent analysis revealed that CAP was localized in liver hepatocytes and kidney tubule epithelial cells in Cd treated tadpoles, and (c) the anti-G-CAP crossreacted with rodent and fish CAP. These observations suggest that the developing liver and mesonephros are involved in responses to toxic metals and that our anti G-CAP antiserum may be used to gauge exposure to environmental Cd. PMID- 1755030 TI - Ten-day repeated-exposure inhalation study of dimethylformamide (DMF) in cynomolgus monkeys. AB - Cynomolgus monkeys showed no measurable adverse effects following inhalation of 500 ppm dimethylformamide (DMF), 6 h/d, 5 d/wk, for 2 weeks either when exposed whole-body or head-only (one monkey per exposure route). Measurement of DMF concentrations into and out of the head-only exposure unit along with measurement of the tidal volume suggest that DMF absorption by the respiratory tract is approximately 100% at a concentration of 500 ppm. Plasma samples taken 1/2 to 18 h after the first exposure show DMF AUC values which were 3 times higher in the monkey exposed by whole-body, indicating considerable absorption by non inhalation route(s). The same comparison of plasma samples taken following the final (10th) exposure similarly had a 6-times DMF AUC value for the monkey exposed by whole-body. From this study it is apparent that the practice of avoiding dermal contact with DMF is important in reducing the likelihood of producing DMF-induced injury in the workplace. PMID- 1755031 TI - Wy-14,643 but not 2-ethylhexanol increases intracellular free calcium in cultured Kupffer cells. AB - Hypolipidemic drugs and phthalic ester plasticizers induce peroxisomes and cause hepatocellular carcinoma in rodents by mechanisms which remain unknown. Recent evidence from this laboratory suggests that many agents in this class of chemicals are uncouplers of mitochondrial oxidative phosphorylation both in vitro and in vivo. Uncoupling of oxidative phosphorylation decreases ATP required for ion pumps and could thereby indirectly increase intracellular free calcium. The goal of these experiments, therefore, was to compare the effect of the potent uncoupler and non-genotoxic carcinogen Wy-14,643 with the weaker agent 2 ethylhexanol on intracellular free calcium in cultured Kupffer cells. Kupffer cells, the resident hepatic macrophages, are activated by calcium and release a variety of mitogenic growth factors that may modulate cell proliferation. In this study, the cytosolic free calcium concentration in Fura-2-loaded cultured Kupffer cells was increased significantly from 78 +/- 11 to 838 +/- 112 nM following incubation with Wy-14,643 (1.25 mM). The increase in intracellular calcium due to Wy-14,643 was both time- and dose-dependent. At equimolar concentrations, ethylhexanol had no effect on intracellular calcium (65 +/- 20 nM). However, at higher concentrations (3 mM), ethylhexanol also increased intracellular calcium. These data suggest that elevation of intracellular calcium in Kupffer cells may be involved in the mechanism of action of this interesting class of non-genotoxic carcinogens. PMID- 1755032 TI - Time course for the elevation of glutathione in numerous organs of L1210-bearing CDF1 mice given the L-cysteine prodrug, RibCys. AB - RibCys, a thiazolidine prodrug of L-cysteine synthesized by the condensation of the sulfhydryl-containing amino acid with the aldose monosaccharide D-ribose, successfully elevated glutathione (GSH) levels in numerous organs of tumor bearing CDF1 mice. GSH content was assayed 1,2,4,8 and 16 h after RibCys administration (8 mmol/kg, i.p.); various organs achieved maximal GSH content at different time points. GSH in the liver was elevated 1.5-fold compared to untreated controls at the 16-h time point. Kidney GSH also was maximal at 16 h and achieved 1.6-times control values. GSH in muscle achieved 2.5 times the levels in control animals, while the bladder was elevated 2.1-fold, and the heart 1.8-fold. Other tissues tested (spleen, pancreas, lung) showed a 1.1- to 1.2-fold increase in GSH content. GSH in implanted L1210 tumors was also elevated only 1.2 fold. These data suggest the possibility of protecting organs other than the liver from toxic insults that require the intervention of GSH for detoxication and may allow such protection without compromising the utility of chemotherapy. PMID- 1755033 TI - Evidence of hepatic conversion of C6 and C8 chlorotrifluoroethylene (CTFE) oligomers to their corresponding CTFE acids. AB - The toxicity of polychlorotrifluoroethylene oil (3.1 oil) hydraulic fluid is believed to be related to the conversion of neutral chlorotrifluoroethylene (CTFE) oligomers to their corresponding halogenated fatty acids. Male Fischer-344 rats were orally gavaged (1.25 g/kg/d) with two batch formulated 3.1 oils (3.1 oil-C6 and 3.1 oil-C6:C8) and C6 CTFE (trimer) and C8 CTFE (tetramer) oligomers, respectively. All rats exposed to test compounds for 7 days demonstrated significant 2-fold increases in liver weight over controls. After 24-h and 7-day dosings, the amount of tetramer acid formed in the liver was 2x and 11x the amount of trimer acid formed, respectively. In addition to the formation of tetramer acid, rats dosed with tetramer also indicated comparable amounts of trimer acid. These data indicate that toxicity induced by the 3.1 oil may be due to the retention of the tetramer and the resulting persistent high concentrations of halogenated fatty acids. PMID- 1755034 TI - Assessment of safety/risk of chemicals: inception and evolution of the ADI and dose-response modeling procedures. AB - This article reviews the procedures for the assessment of safety/risk of chemicals to human health. Because the nature and severity of toxicity and the extent of the database vary from chemical to chemical, the assessment is done on a case by case basis. Essentially 5 steps are involved in the assessment: (a) identification of hazards based on appropriate human and animal data; (b) determination of the dose-response relationship of the adverse effects of the chemical; (c) extrapolation of the dose-response data from test subjects to human populations; (d) estimation of the exposure; and (e) assessment of the safety/risk of the chemical under a specified exposure. Emphasis in this article, however, is placed on the extrapolation of the dose-response data to the human situation. The extrapolation is done by the identification of a no-observed adverse-effect level (NOAEL) and the application of a safety factor, thereby arriving at an acceptable daily intake (ADI). The safety factor is selected on the basis of, inter alia, the severity of the adverse effect and the adequacy of the database. On the other hand, with genotoxic carcinogens, mathematical modeling is used for extrapolation. This is because the effects of genotoxic carcinogens are generally believed to have no threshold. The ADI approach, which involves the identification of a NOAEL, is therefore not applicable. A number of mathematical models have been developed to assess, from the dose-response data, either the risks that may be associated with a specified dose, or the 'virtually safe dose' at a specified risk level. The evolution, application and shortcomings of these procedures and the potential improvements in the ADI approach and in the dose-response characterization based on these mathematical models are also discussed. PMID- 1755035 TI - Benzo[e]pyrene pretreatment of immature, female C57BL/6J mice results in increased bioactivation of aflatoxin B1 in vitro. AB - Hepatic microsomes were prepared from immature C57BL/6J mice 24 h after receiving intraperitoneal injections of either corn oil, benzo[e]pyrene (BeP, 50 mg/kg) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 4 x 10(-3) mg/kg). The capacity of these hepatic microsomes to bioactivate aflatoxin B1 (AFB1), 2-aminoanthracene (AA), benzo[a]pyrene (BaP), 3-methylcholanthrene (MC), 7,12 dimethylbenzanthracene (DMBA), BeP and pyrene (PY) was measured using strain TA100 in the Salmonella typhimurium/microsome reversion assay. BeP pretreatment of mice resulted in a 33% increase in mutagenic potency (MP) of AFB1 over the corn oil controls and a 70% increase in MP relative to TCDD-pretreated microsomes. With AA, BaP and DMBA as promutagens, BeP pretreatment reduced MP an average of 24%, while TCDD pretreatment increased MP of these 3 promutagens 263% compared to controls. Since the general effects of BeP and TCDD on murine hepatic cytochrome P-450 (P450)-mediated activities in this study were discordant, it appears that changes in P450 activity by BeP pretreatment are not mediated through the Ah receptor. PMID- 1755036 TI - Neurotoxic effects of 2,5-hexanedione on growing peripheral nerve axons of rat fetuses. AB - Peripheral nerves of rat fetuses were used to investigate the potential neurotoxicity of 2,5-hexanedione (2,5-HD) on developing axons. Pregnant female Sprague-Dawley rats were injected subcutaneously with 680 mg/kg of 2,5-HD once a day from day 12 of gestation (GD12) through GD16. On GD20 live fetuses were removed from the uterus, and the sciatic nerves were examined morphologically. Upon electron-microscopy affected nerves showed axons which were aggregated and fused together; the number of large axons was increased, but there were no axons aggregated with neurofilaments. PMID- 1755037 TI - Depletion of brain serotonin does not alter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced starvation syndrome in the rat. AB - We have previously reported a series of biological events in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-intoxicated rats which resulted in elevated brain serotonin (5-HT) levels, offering a possible explanation of the acute toxicity (reduced feed intake and death) in these animals. It was thus hypothesized that depletion of central 5-HT stores should alter the TCDD-induced starvation syndrome. Brain 5-HT was selectively depleted by intracerebroventricular infusions of the neurotoxin 5,7-dihydroxytrytamine (5,7 DHT). Subsequently the animals were given a lethal dose of TCDD. In rats treated with 5,7-DHT hypothalamic 5-HT was depleted up to 90% compared to control animals, yet TCDD induced the expected reduction of bodyweight and feed intake. These results suggest that although TCDD increases central 5-HT levels as a result of increased plasma tryptophan, this may not be the main cause for reduced feed intake and lethality in these animals. PMID- 1755038 TI - Regulation of metallothionein production in HeLa cells. AB - Metallothioneins are cysteine-rich, heavy-metal-binding proteins which have been assumed to participate in the detoxification of toxic metals. The mechanism of thionein (apoprotein of metallothionein) induction by cadmium was studied using cultured human cells. It was found that when thionein synthesis reaches a maximum (6-8 h after induction), it no longer responds to additional cadmium. Changes in cadmium uptake or induction of inhibitory proteins were not responsible. Together with our previous findings, a possible mechanism is proposed: loss of the secondary induction response might be due to increased intracellular levels of thionein, which has been overproduced by the initial induction. PMID- 1755039 TI - Defluorination of the CFC-substitute 1,1,1,2-tetrafluoroethane: comparison in human, rat and rabbit hepatic microsomes. AB - 1,1,1,2-Tetrafluoroethane (HFC-134a), which lacks ozone-depleting potential, has been selected as a replacement refrigerant for dichlorodifluoromethane (CFC-12) in air-conditioning and chiller applications, and as a propellant for pharmaceutical aerosols. A variety of paradigms using rats and rabbits have shown that HFC-134a has very little toxic potential. To strengthen the prediction of human hazard associated with HFC-134a exposure, we evaluated the rate of metabolism of this halocarbon by human hepatic microsomes relative to similar tissue preparations derived from rats and rabbits. Human microsomes defluorinated HFC-134a in a cytochrome-P-450-catalyzed reaction, common also to rat and rabbit. In absolute terms, the maximal rate of HFC-134a metabolism by human microsomes was very low, showed little interindividual variation among the samples evaluated (1.3 +/- 0.3 nmol F-/mg protein/15 min, mean +/- SD, n = 10), and did not exceed that in rat or rabbit liver microsomes. These findings support the argument that for characterization of HFC-134a toxicity, especially that which may be mediated by products of halocarbon metabolism, laboratory animals are an adequate surrogate for humans. PMID- 1755040 TI - Human parasitology in Czechoslovakia. PMID- 1755041 TI - Malaria morbidity and mortality in children under three years of age on the coast of Benin, West Africa. AB - Malaria morbidity and mortality were measured in a population of 1500 children under 3 years of age from April to December 1989. During monthly home visits, an average of 26 children in 1000 had fever, of whom 15 had parasitaemia. Children less than 6 months old had significantly fewer fever episodes, whether associated with parasitaemia or not. Overall, prevalence of fever with parasitaemia rose steadily from April to August, then decreased but reached a second peak in November. Peaks coincided with the 2 rainy seasons in April to June and September to October. Comparison with a control group demonstrated that children with parasitaemia exceeding 1000 infected red blood cells per microliter of blood had fever significantly more often than children with lower levels of parasitaemia. The average number of fever episodes per child per year was 2.4, and 33% of these were estimated to be caused by malaria. All cause mortality was 26/1000/year and the malaria mortality rate was 8/1000/year. Malaria deaths were most frequent in the second year of life. PMID- 1755043 TI - Paraphimosis apparently associated with Plasmodium falciparum infection. PMID- 1755042 TI - Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria endemic region of west Africa. AB - We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity. PMID- 1755044 TI - A prospective clinical trial of the treatment of falciparum malaria with mefloquine, with special reference to neuro-psychiatric side effects. PMID- 1755045 TI - A case of Plasmodium falciparum malaria sensitive to chloroquine but resistant to pyrimethamine/sulfadoxine in Sennar, Sudan. PMID- 1755046 TI - Potentiation of monodesethylamodiaquine and amopyroquine with desipramine against Plasmodium falciparum in vitro. PMID- 1755047 TI - Trial of antimalarial potential of extracts of Artemisia annua grown in Myanmar. PMID- 1755048 TI - Detection of mature malaria infections in live mosquitoes. AB - A method has been developed which detects malaria parasites in the salivary glands of live Anopheles stephensi. The method exploits the sugar feeding behaviour of the mosquito and requires only routine Western blotting techniques on nitrocellulose membrane (NCM). Infectivity can be determined without any direct manipulation of individual mosquitoes. Female A. stephensi were infected with the rodent malaria parasite, Plasmodium berghei, and after 14-16 d were starved of fructose overnight (12-18 h), then resupplied with fructose presented through a small piece of NCM. Mosquitoes were allowed to probe the membrane for several hours; the NCM was then removed and subjected to a standard immunoblotting protocol using an anti-P. berghei circumsporozoite protein (CSP) monoclonal antibody as the primary reagent, and a horseradish peroxidase-coupled secondary antibody. NCMs taken from cages containing infected mosquitoes showed a variable number of small black dots where individual females had probed and deposited either CSP or sporozoites. Infectivity could be detected easily from 13 14 d after feeding, and in as few as 10 mosquitoes at 19 d after infection; in one instance, infection in a single mosquito was clearly determined. After blocking with goat serum, the NCMs could be stored for 3-4 months and still provided positive reactions, offering some potential for applicability to field research studies. PMID- 1755049 TI - Genetic evidence for the importance of interrupted feeding by mosquitoes in the transmission of malaria. AB - Plasmodium falciparum isolates were obtained from 17 pairs of Gambian children, each pair living in the same house and presenting with malaria at the same time. Frequencies of allelic serotypes of 3 polymorphic blood stage proteins (MSP1, MSP2, and Exp-1) were previously determined from a large number of isolates from patients in the local area, and the probability of a random pair of isolates containing an identical genotype was calculated to be less than 0.01. However, 3 of 8 household pairs in one year, and 6 of 9 in the next year, contained identical P. falciparum genotypes, a much higher frequency than expected randomly (P less than 0.00005, for each year). This finding is discussed in terms of the probable contribution of single mosquitoes infecting more than one person. PMID- 1755050 TI - Studies on the leishmaniases in the Sudan. 3. Clinical and parasitological studies on visceral and mucosal leishmaniasis. AB - The epidemiological, clinical and laboratory findings of 27 patients with visceral leishmaniasis (VL) and six with mucosal leishmaniasis (ML) in Sudan are described. The diagnosis was confirmed by the demonstration of amastigotes in bone-marrow in 20 cases with VL (80%) and impression smears in 2 cases with ML. The enzyme-linked immunosorbent assay and direct agglutination test were positive in all the sera tested. The leishmanin test was positive in all patients with ML, the diameter of the reaction ranging from 18 to 28 mm (mean 23 mm). Only one isolate (from a patient with VL) grew sufficiently well in culture to be typed and this was characterized by isoenzyme electrophoresis as Leishmania donovani zymodeme LON-46. The possibility that the ML isolate could have been L. major zymodeme LON-1 is discussed. The importance of further research to isolate and identify by biochemical procedures a more representative range of isolates of Leishmania from different clinical types in the Sudan, in order to elucidate questions such as the relationship between the vectors and possible animal reservoirs, is emphasized. PMID- 1755051 TI - Post-kala-azar anterior uveitis: demonstration of Leishmania parasites in the lesion. PMID- 1755052 TI - Direct agglutination test for diagnosis and sero-epidemiological survey of kala azar in the Sudan. AB - 132 patients with suspected kala-azar (visceral leishmaniasis) were included in a prospective study to compare the performance of the direct agglutination test (DAT) with smears of lymph node, bone marrow and splenic aspiration. A titre greater than 1:3200 was considered positive. 67 patients provided positive smears and 65 were smear-negative. Compared with the results obtained from smears, the sensitivity of the DAT was 94% and its specificity 72%. Of 18 patients who were negative by smears but positive by DAT, 3 were treated on strong clinical suspicion of kala-azar and responded well to therapy. One other patient had post kala-azar dermal leishmaniasis. Of the remaining 14, 8 were tested with the leishmanin skin test; 6 gave a positive result, suggesting past or sub-clinical infection. In 4 smear-positive patients, the DAT was negative; in 2 of these, the test remained negative during 6 months' follow-up. In a sero-epidemiological survey in a camp for displaced people, 30 of 600 sampled individuals gave a positive DAT. Of these, 11 had been treated for kala-azar; 4 others were leishmanin positive. The DAT is a useful screening test (sensitivity 94%; predictive value of a negative test 92%), but it does not differentiate between past kala-azar, sub-clinical infection and active disease. PMID- 1755053 TI - Indirect fluorescent immunoassay in the diagnosis of infantile and adult kala azar. PMID- 1755054 TI - Human urine stimulates growth of Leishmania in vitro. AB - Enhancement of trypanosomatid metacyclogenesis by insect urine components led us to test the effect of human urine as a culture additive. The addition of 1-5% urine to Schneider's Drosophila medium containing 10% foetal calf serum enhanced the growth of 11 Leishmania strains representing 8 different taxonomic groups. Cell division was stimulated in cultures with non-dividing organisms. Peak cell density was increased, as was the efficiency with which L. donovani could be isolated from infected hamsters. Preliminary work suggested that the modified medium would be useful for field isolation of L. donovani and L. braziliensis. The active nutrients or growth factors are not known. PMID- 1755055 TI - Granulomatous encephalitis due to a leptomyxid amoeba. PMID- 1755056 TI - Differences in the rate of hepatosplenomegaly due to Schistosoma mansoni infection between two areas in Machakos District, Kenya. AB - The relationship between intensity of Schistosoma mansoni infection and the degree of related morbidity was suspected to differ locally within the Machakos district of Kenya. To test this possibility, prevalences of hepatomegaly and splenomegaly among 1483 school children were compared between 2 areas, Kangundo and Kambu, within this district. These areas, which were similar in many geographical and economic respects and populated by the same tribe (Akamba), had comparable levels of S. mansoni infection and no S. haematobium infection. A relationship was observed between the prevalence of hepatomegaly and intensity of S. mansoni infection, which showed no consistent difference between the 2 areas. In contrast, a relationship between the prevalence of splenomegaly and intensity of S. mansoni infection was observed only in the Kambu schools, and not in the Kangundo schools where the overall prevalence of splenomegaly was much lower. It was possible that part of the splenomegaly observed in Kambu was due to malaria. However, the observation that malaria and schistosomiasis in 2 Kambu schools were not positively correlated allowed approximations to be made of the relative contributions of each to the prevalence of splenomegaly. It was concluded that, in a school close to the river that formed the main transmission site of S. mansoni, schistosomiasis-related hepatosplenomegaly was present in at least 17% of children. The reason for the high prevalence in Kambu of hepatosplenic schistosomiasis remains uncertain, but it could include a synergistic interaction of schistosome infection with malaria. PMID- 1755057 TI - Eosinophilia and eosinophil helminthotoxicity in patients treated for Schistosoma mansoni infections. AB - The changes in eosinophil levels and in eosinophil-mediated antibody-dependent schistosomular cytotoxicity, following treatment for Schistosoma mansoni infections, have been investigated in 2 similar groups of patients aged 15-50 years. Patients in group 1 were treated with either hycanthone or oxamniquine, and those in group 2 with hycanthone or praziquantel. Eosinophil levels were significantly increased in both groups. In group 1 peripheral blood eosinophil counts rose from a mean of 175/microliters before treatment to 745/microliters 3 weeks after treatment, and in group 2 from 181/microliters to 1066/microliters. The increase in eosinophil levels was positively correlated with a rise in circulating anti-adult worm antibodies (r = -0.587, P less than 0.05), whereas a negative correlation was recorded with anti-egg antibodies (r = -0.727). Despite some enhanced eosinophil helminthotoxicity following treatment in some of the individuals in group 1 (7/15), the change overall was not significant. In group 2, in which a different standard anti-schistosomular antibody was used, the eosinophil killing capacity recorded at 3 weeks was lower than that before commencement of treatment (t = 2.89, P less than 0.01). The eosinophil stimulating activity, detected in cultured mononuclear cell supernatants (MCS) from individual patients, correlated with eosinophil levels (r = 0.582, P less than 0.02) but there was no association with eosinophil killing. MCS activity did not appear to be boosted by treatment. These studies showed that peripheral blood eosinophil counts were increased following treatment, but their ability to kill schistosome larvae is variable and may depend on the immune serum used as the source of anti-schistosomular antibody. PMID- 1755058 TI - Onchocerciasis in Malawi. 1. Prevalence, intensity and geographical distribution of Onchocerca volvulus infection in the Thyolo highlands. AB - Skin snips from 23,373 persons living in the Thyolo (formerly Cholo) highlands focus of southern Malawi showed infection with Onchocerca volvulus to be unevenly distributed within the highland area. In the centre of the focus most adults were infected, though intensity of infection was light, not exceeding a geometric mean of 8 microfilariae per mg of skin. It was estimated that 327,000 persons live in areas where prevalence of infection exceeds 10% and, of these, 94,500 persons over the age of one year are infected with O. volvulus. There is a significant relationship between infection with O. volvulus and bilateral blindness in the Thyolo focus, although the number of persons blind from onchocerciasis is probably less than 300. PMID- 1755059 TI - A community trial of ivermectin for onchocerciasis in Sierra Leone: adverse reactions after the first five treatment rounds. AB - We have studied the adverse reactions reported after ivermectin in 1745 villagers in southern Sierra Leone, allocated at random to receive ivermectin or placebo and treated 'double-blind' with 4 doses at six-monthly intervals. Six months after the fourth dose all eligible villagers received ivermectin regardless of their previous treatment. At the first treatment round more adverse reactions were reported by villagers treated with ivermectin than by those who received placebo. Reactions occurred most often on the second day after treatment. There were significant correlations between an individual's skin microfilarial load and the risk of developing adverse reactions. On re-treatment there was no significant excess of reported adverse reactions in the ivermectin group compared to the placebo group. Unlike other adverse reactions, the risk of cutaneous reactions after the first dose of ivermectin was not correlated with skin microfilarial load. In addition, after re-treatment with ivermectin, cutaneous reactions were reported significantly more often than with placebo. We confirm that ivermectin is safe for mass distribution, but adverse reactions should be monitored and treated after the first dose. Throughout this study ivermectin was well tolerated, with significantly more villagers returning for re-treatment after ivermectin than placebo, and all adverse reactions were self-limiting or successfully managed with symptomatic treatment. We question whether strict clinical monitoring should be routine at re-treatment, when only cutaneous reactions were consistently reported. If clinical monitoring could be used more selectively, distribution campaigns might be easier to manage and more cost effective. PMID- 1755060 TI - A quantitative approach to the relationship between Wuchereria bancrofti microfilaria counts by venous blood filtration and finger-prick blood films. AB - Counts of nocturnally periodic Wuchereria bancrofti microfilariae (mf) in 20 mm3 finger-prick blood films were compared with membrane counts after filtration of 1 ml of venous blood for their efficacy in determining the prevalence of Bancroftian filariasis. The technique used for spreading and staining the blood films was critically important to the sensitivity of this screening procedure. There was good agreement between the 2 methods. Four statistical approaches were used to measure the correlation between the 2 sampling methods: 2 linear regression methods using untransformed and transformed data, and 2 non-parametric rank correlation methods. Based on the statistical analyses, this study strongly supports the general observation that finger-prick blood samples tend to contain more mf than equivalent volumes of venous blood, at mf densities high enough to be detectable by the finger-prick technique. It also demonstrates that finger prick samples provide good estimates of mf densities and prevalence of infection except in areas of very low mf densities, where the membrane filtration method would provide a more accurate estimate of prevalence. Regression analyses using untransformed and transformed data, and the rank correlation tests, demonstrated a strong statistically significant correlation (P less than 0.001) between venous and finger-prick mf counts. PMID- 1755061 TI - Antigenic cross-reactivity between Necator americanus and Ascaris lumbricoides in a community in Papua New Guinea infected predominantly with hookworm. AB - Sero-epidemiological data are presented in which antigenic cross-reactivity between Necator americanus and Ascaris lumbricoides has been investigated in a community in Papua New Guinea infected predominantly with N. americanus. It is our contention that the antigenic cross-reactivity which undoubtedly exists between these species accounted for (i) a peak in antibody levels against N. americanus in 10-13 years old children (driven by infection with A. lumbricoides), and (ii) the maintenance of apparent antibody levels against A. lumbricoides in older age groups (driven by infection with N. americanus in the absence of overt infection with A. lumbricoides). Cross-reactivity was analysed further, and apparently N. americanus-specific epitopes identified, by immunoblotting. These observations could have considerable bearing on the interpretation of data from sero-epidemiological studies which failed to take account of concurrent infection with these parasites. PMID- 1755062 TI - Gelatin particle indirect agglutination test for mass examination for strongyloidiasis. AB - An indirect agglutination test using recently developed gelatin particles was assessed to determine its applicability as a screening test for mass examination for strongyloidiasis. 1199 individuals in Sashiki Town, Okinawa Island, were screened by the test and 34.7% were determined to be antibody positive. Follow-up examination of the persons whose sera showed positive antibody responses demonstrated the presence of faecal larvae in 41.7%. The calculated infection rate (14.5%) was similar (14.1%) to that indicated by another survey using the micro-enzyme-linked immunosorbent assay (micro-ELISA), conducted simultaneously among the inhabitants. The indirect agglutination test was simple to perform in a short time and without specialized equipment. Additionally, the gelatin particles have many advantages as an antigen carrier, e.g. in handling, reading of the resulting pattern, and stable, long-term preservation. The test was considered to be more convenient than the micro-ELISA for mass screening for strongyloidiasis. PMID- 1755063 TI - A controlled chemotherapeutic intervention trial on the relationship between Ascaris lumbricoides infection and malnutrition in children. AB - A 2-year investigation, consisting of a controlled, non-blind, 3-monthly chemotherapeutic intervention trial, based on transmission dynamics of Ascaris lumbricoides infection, was undertaken to prove or refute the role of A. lumbricoides as a contributor to childhood malnutrition. The study involved 1206 children aged 2-12 years in 21 villages in Myanmar [Burma] starting in August 1984. The intervention and non-intervention villages were comparable regarding almost all the important baseline variables, including prevalences of Ascaris infection (80.8 vs 83.0%) and of malnutrition of grade 2 and above for height-for age (58.4 vs 55.8%) and for weight-for-age (48.2 vs 47.8%). The intensity of Ascaris infection was related to the degree of malnutrition. A significant increment of height gain was found, starting after the 6th month, and of weight gain after the 24th month, of the study among the treated 2-10 years old children when compared with the non-treated ones. By the end of 24 months, the height and weight gains per child were 0.65 cm and 0.93 kg respectively. Lesser increments in height-for-age and weight-for-age were also observed after successive treatments among the treated children with initially higher mean worm burdens. The findings are discussed in the context of causal relationship between ascariasis and malnutrition in children. PMID- 1755064 TI - Taeniasis-cysticercosis in Honduras. AB - Data on human taeniasis and human and animal cysticercosis from Honduras were gathered from laboratory, medical and slaughterhouse records, proglottid identification and surveys. The infection rate for human taeniasis was 2.7/1000 individuals at the University Hospital, 10/1000 in the southern provinces of Choluteca and Valle, and 0.6/1000 in Cortes and Atlantida in the north. In surveys, the rates found ranged from 14 to 62/1000 in 9 of 15 communities studied. Taenia solium was identified in 135 of 181 individuals (74.5%) who submitted proglottids for speciation, 23 of whom were children 0-5 years old. The male:female ratio of infection rate was 1:2. The rates of infection with cysticercosis in pigs and cattle at one abattoir in 1981-1986 were 5% and 0.05% respectively. Diagnosis of human cysticercosis at the University Hospital increased five-fold with the introduction of computerized tomography and an enzyme-linked immunosorbent assay: 22 cases were diagnosed in 1980-1984 and 107 cases in 1985-1988. Rates at the neurosurgical ward were higher (29/1000 patients) than in the general hospital census (1.6/1000 patients). aeniasis cysticercosis may be a serious health problem in some areas of Honduras. PMID- 1755065 TI - A purified Fasciola gigantica worm antigen for the serodiagnosis of human fascioliasis. AB - Partially purified Fasciola gigantica worm antigens were evaluated in an enzyme linked immunosorbent assay (ELISA) for the specific serological diagnosis of fascioliasis. The diagnostic potential of 10 antigen fractions derived from gel filtration peaks (II & III) were evaluated individually or in combination against a panel of admission sera obtained from 50 patients subsequently diagnosed as having a variety of systemic parasitic diseases, and from 10 healthy volunteers with no recent history of parasitic infections. Fractions 2 and 10 were highly specific for Fasciola infection and failed to react with sera from any patient with other parasitic diseases or from controls. All other fractions exhibited reactivity with the majority of sera from the fascioliasis patients, but also with some sera from patients infected with other parasites. Based on these results, the ELISA, as outlined here, should be considered as a rapid and specific technique for the diagnosis of fascioliasis and also as an epidemiological surveillance technique in areas endemic for F. gigantica infection. PMID- 1755066 TI - Human Opisthorchis and Haplorchis infections in Laos. AB - A study of the epidemiology of trematode infections was carried out in Vientiane province, Laos, comprising examination of snails, fish, cats, and human stools. Opisthorchis viverrini cercariae were found in the snail Bithynia siamensis goniomphalus (Bithyniidae) and Haplorchis taichui cercariae in Tarebia granifera (Thiaridae). O. viverrini metacercariae were recorded in the flesh of 7 species of cyprinid fish; metacercariae of the heterophyid fluke Haplorchis taichui were found in 4 species of cyprinid fish and those of H. pumilio in 2 species. Cats from the same localities were infected with O. viverrini and 4 species of heterophyid flukes, frequently as multiple infections. The highest prevalence of small fluke eggs in human stools was recorded in the 20-29 years age group, particularly in males (90.4%). Three-quarters of human infections were light (less than 1000 eggs/g), the highest value (2975 eggs/g) being recorded in the 10 14 years age group. Identification of small flukes excreted by Laotian patients after treatment with praziquantel in Czechoslovakia revealed more cases with H. taichui than with O. viverrini. The results confirmed the simultaneous occurrence of O. viverrini and intestinal heterophyid flukes in the area studied. PMID- 1755067 TI - High prevalence of anti-hepatitis delta virus antibody in chronic liver disease in Somalia. AB - We have assessed the prevalence of hepatitis delta virus (HDV) infection in people with histologically proven chronic liver disease living in Somalia. Among 104 patients studied (14 with chronic persistent hepatitis, 74 with chronic active hepatitis, and 16 with active cirrhosis), 52 were positive for hepatitis B surface antigen; of these, 26 (50%) carried anti-delta antibodies. HDV infection was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (60.9%) than in HBeAg positive patients (9.1%). Using the dot-blot hybridization technique, serum hepatitis B virus deoxyribonucleic acid was revealed in 73.1% of patients without HDV infection, while it was detected in only 7.7% of anti-delta positive patients. It is concluded that HDV is strongly associated with chronic liver disease in Somalia. PMID- 1755068 TI - Epizootic of fox rabies in the Sultanate of Oman. PMID- 1755070 TI - A rapid test for Salmonella in stools, not requiring refrigeration. PMID- 1755069 TI - Identification of Vibrio cholerae by enzyme electrophoresis. AB - Zymovar analysis of 260 strains of Vibrio cholerae plus 3 reference strains of V. mimicus, using 13 structural loci, led to the grouping of strains in 73 zymovars (strain or group of strains sharing the same alleles). Effective separation of strains, distinction of V. cholerae strains from closely related V. mimicus and the detection of 2 vibrio strains, including one with two O1 serovars, in supposedly pure collection cultures, illustrate the potential of zymovar analysis in the identification of V. cholerae isolates. Two El Tor strains from USA, one CT+ and the other CT-, shared the same zymovar 71, while 127 typical El Tor strains belonged to zymovar 14. PMID- 1755072 TI - A field study of the effects of ivermectin on ectoparasites of man. PMID- 1755071 TI - Distribution and prevalence of Tunga penetrans in coastal south Trinidad, West Indies. PMID- 1755073 TI - Fatal extradural haematoma after snake bite (Bothrops moojeni). PMID- 1755074 TI - Non-ulcer dyspepsia in Nigeria: a case-control study. AB - Non-ulcer dyspepsia is common in Africa, yet there are few data on its possible cause. In this study 40 patients with strictly defined non-ulcer dyspepsia were matched with 40 asymptomatic volunteers. Both groups were questioned concerning their intake of alcohol, cola nut, non-steroidal anti-inflammatory drugs, and smoking. They then underwent upper gastrointestinal endoscopy with mucosal biopsy of the gastric mucosa: these biopsies were examined for gastritis and Helicobacter pylori. Ingestion of cola nut was the only statistically significant difference between the two groups. A high prevalence of gastritis and H. pylori infection was found in both groups, suggesting that these factors are not important in the aetiology of non-ulcer dyspepsia in northern Nigeria. PMID- 1755075 TI - Toxocara canis and pregnancy in mice. PMID- 1755076 TI - Sulfadoxine-pyrimethamine for the treatment of malaria. PMID- 1755077 TI - Cutaneous leishmaniasis and Leishmania infantum. PMID- 1755078 TI - Mebendazole in giardial infections: confirmation of the failure of this treatment. PMID- 1755079 TI - Reinfection of Somali children with Trichuris trichuria: a reply. PMID- 1755080 TI - Prevention of transfusion-transmitted malaria: is it time to revisit the standards? PMID- 1755081 TI - White cell-reduced blood components: should we go with the flow? PMID- 1755082 TI - A multicenter study on the efficiency of white cell reduction by filtration of red cells. AB - To evaluate accurately the current performance of filtration, the French Produits Sanguins Labiles study group, composed of 21 transfusion teams, conducted a large scale 6-month study involving over 1400 filtrations and 3000 controls. Some 745 standard red cell concentrates (RBC concentrates) and 690 concentrates previously white cell (WBC)-reduced by removal of buffy coat (BC-poor RBC concentrates) were filtered using six commercially available filters: at least 170 results were collected per filter, spread among a minimum of three teams. Prefiltration controls show that the removal (manual and automated) of the buffy coat results in an initial WBC reduction of approximately 63 percent, along with a hemoglobin loss of 4 g (7%). After filtration, residual WBCs were counted in the Nageotte manual counting chamber. The reliability of this counting method, which is simple and adapted to low WBC concentrations, was characterized in this study by a 25 percent coefficient of variation (CV) for a concentration of 2.5 WBCs per microL (i.e, 0.6 x 10(6) WBCs/filtered unit). The analysis of the results shows that, for five of six filters (1 filter was excluded), the postfiltration median value of residual WBCs was 1.1 x 10(6) in filtered RBC concentrates (n = 590), whereas it was 0.34 x 10(6) in filtered BC-poor RBC concentrates (n = 581). The difference is significant (p less than 10(-8), Wilcoxon test). Hemoglobin loss due to filtration varies according to the filter, from 5.7 +/- 2.2 to 17.3 +/- 2.5 g.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755083 TI - Reassessment of blood donor selection criteria for United States travelers to malarious areas. AB - In the United States (US), travelers who have had malaria or who have taken antimalarial chemoprophylaxis are deferred as blood donors for 3 years to prevent transfusion-transmitted malaria. To assess the impact of shortening this 3-year exclusion period, national malaria surveillance data from 1972 to 1988 were reviewed. The average annual rate of transfusion-transmitted malaria is 0.25 cases per million units of blood collected. Of 45 reported cases, 38 percent were caused by Plasmodium malariae, 29 percent by P. falciparum, 24 percent by P. vivax, and 9 percent by P. ovale. Thirty-two donors were implicated in 34 cases of transfusion-transmitted malaria. Of 30 implicated donors whose native country was identified, 23 (77%) were foreign nationals and 7 (23%) were from the US. In a review of all imported malaria cases by species and by interval between date of entry and onset of illness, 98 percent of P. falciparum, 86 percent of P. malariae, 76 percent of P. vivax, and 74 percent of P. ovale infections became symptomatic within 6 months of the patient's arrival in the US, regardless of the use of prophylaxis. Shortening to 6 months the donor exclusion period for US travelers to malarious areas would result in a minimum of 70,000 additional blood donors' being made available, with a maximum annual increase of 0.03 additional cases of transfusion-transmitted malaria. The potential benefit of bringing healthy travelers back into the donor pool after a shorter period of exclusion merits consideration by the blood banking industry. PMID- 1755084 TI - Reduced membrane protein methylation in red cells of the McLeod blood group phenotype. AB - Red cells (RBCs) contain an abundance of protein methylase II, which catalyzes the transfer of methyl groups from S-adenosylmethionine to carboxyl groups of aspartyl and glutamyl residues in proteins. Enzyme-catalyzed transfer of methyl groups, labeled with 14C or 3H, from S-adenosylmethionine to membrane proteins of McLeod, Ko, and control RBCs was assayed by determining the acceptance of labeled methyl groups under standardized conditions. Membranes of control cells and Ko cells showed about 50 percent greater uptake than did those of McLeod cells. However, when ovalbumin was used as a methyl-accepting substrate, the levels of protein carboxymethyltransferase activity in all three types of cells were found not to differ significantly. In addition, no significant qualitative differences were apparent when methyl-labeled polypeptides from control and McLeod cells were separated by slab gel electrophoresis. The mechanisms responsible for changes in membrane protein methylation of McLeod cells remain unclear. However, these observations provide further evidence of the pleiotropic biochemical lesion associated with the acanthocytic morphology that characterizes McLeod RBCs. PMID- 1755085 TI - Probable reasons that autologous blood was not donated by patients having surgery for which crossmatched blood was ordered. AB - Preoperative autologous blood donation is used by only a small percentage of surgery patients for whom crossmatched blood is ordered. To document the reasons the patients failed to donate, the medical records of surgical patients at three university and three community hospitals were studied. All procedures for which crossmatched blood was ordered, but for which autologous blood was not available, were included (n = 8121). Probable reasons for nondonation were found in 72 percent of university hospital patients and 65 percent of community hospital patients (n = 6064 and n = 2057, respectively). The most frequent reasons for nondonation among university hospital patients were emergency surgery (27%) and age less than 12 years (17%), and those among community hospital patients were emergency surgery (42%) and American Society of Anesthesiologists physical status greater than or equal to 4 (20%). Surprisingly, anemia (hemoglobin less than 11 g/dL [less than 110 g/L]) as the only limitation to donation was rarely found: this was the sole reason in only 3.3 percent of university hospital and 4.5 percent of community hospital patients. Overall, of 8121 patients who failed to donate autologous blood, 5731 (71%) had legitimate medical reasons. The remaining 2390 (29%) had no identifiable reason for nondonation, and recruitment efforts should be focused on them and their surgeons. PMID- 1755086 TI - Prevalence of antibody to Trypanosoma cruzi among blood donors in Los Angeles, California. AB - Transfusion-associated Chagas' disease is a serious public health problem in Central and South America. With the recent influx of immigrants from Chagas' disease-endemic areas, concern about the risk of disease from blood transfusion has increased in the United States. To assess the prevalence of Trypanosoma cruzi infection in one area, 1024 consecutive blood donations from 988 voluntary blood donors at a medical center in Los Angeles County were screened serologically. The median age of donors screened was 32.5 years; 53.4 percent were male, and 38.4 percent were born in Chagas' disease-endemic countries. All donor sera were tested by complement fixation (CF) and indirect immunofluorescence (IIF) tests. A radioimmunoprecipitation assay (RIPA) was also done on all sera from CF- or IIF reactive donors and an equal number of sera from nonreactive donors. A second serum specimen was obtained, and interviews were completed for 18 (67%) of 27 donors with an initial CF titer greater than or equal to 8 or an IIF titer greater than or equal to 64. The overall seroreactivity (by CF and IIF) was 1.1 percent (11/988). One donor (0.1%) had antibody specific to the 72- and 90-kDa antigens of T. cruzi on RIPA. Seven recipients of blood components from the seroreactive donors were located and were seronegative at 3 to 6 months. Seroreactive donors were 3.6 times more likely to have been born or to have resided in Mexico or Central America, 8.7 times more likely to have donated blood in the past, and 11.8 times more likely to have a history of malaria prophylaxis or treatment. PMID- 1755088 TI - Validating the probability of paternity. AB - In cases of disputed parentage, it is commonly thought that the probability of paternity (P) represents the probability that the tested man is the biologic father of the child whose parentage is in doubt and that the paternity index (PI) is the likelihood ratio that enters into this probability. Using the results of HLA typing in a sample of disputed parentage cases, the distribution of P was examined within two groups: actual mother-alleged father-child trios, and simulated mother-unrelated man-child trios. These distributions were found to be roughly consistent with the usual understanding of P. PMID- 1755087 TI - Effects on donors of second bone marrow collections. AB - Second bone marrow transplants have been used successfully to treat marrow graft failure or relapse following the original marrow transplantation. Hospital records of 16 related two-time bone marrow donors were reviewed to determine what risks a person faces in making a second marrow donation. One donor suffered a minor complication following the first collection, but no donors suffered complications during the second donation. The volume of marrow collected for the first and second donations (1253 +/- 504 vs. 1261 +/- 471 mL) was similar. However, more marrow donors received transfusions of homologous red cells during the second collection than during the first collection (5/16 compared to 1/16; p = 0.06). To determine what factors might contribute to the high incidence of homologous red cell transfusion during second donations, the experiences of donors who received homologous blood during the second donation were compared to the experiences of donors who received only autologous blood. Persons receiving homologous blood during the second collection received more red cell units than persons receiving autologous blood (2.0 +/- 0.7 units compared to 0.9 +/- 0.5 units; p less than 0.01). Their precollection hemoglobin levels were lower (12.3 +/- 1.2 vs. 14.4 +/- 1.4 g/dL [123 +/- 12 vs. 144 +/- 14 g/L]; p less than 0.01), and the time between the first and second collections was significantly less (45 +/- 8 days vs. 342 +/- 432 days; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755089 TI - A flow cytometric method for determination of white cell subpopulations in filtered red cells. AB - A flow cytometric method for the detection of low amounts of lymphocytes, monocytes, and granulocytes in filtered red cells (RBCs) was evaluated. In this procedure, the RBCs in the samples were lysed by ammonium chloride treatment and the white cells (WBCs) were detected by flow cytometry according to their specific light-scattering properties. The identity of the WBC subpopulations was confirmed by immunofluorescence with monoclonal antibodies specific for each cell type. Flow cytometric determination of WBCs in filtered RBCs correlated with numbers obtained by both a hemocytometer (r = 0.76) and a radioimmunoassay (r = 0.79). Total numbers of WBCs in RBCs measured by flow cytometry were 59 +/- 13 percent (n = 7) of those measured by electronic particle counting, 32 +/- 6 percent (n = 25) by hemocytometer, and 48 +/- 11 percent (n = 29) by radioimmunoassay. Lymphocytes added to filtered RBCs in a concentration of 1.37 cells per microL were detected at an average of 0.56 +/- 0.22 cells per microL (n = 3). Results with monoclonal antibodies indicated an altered expression of membrane markers on granulocytes after RBC filtration, as seen with cell activation. The inefficiency of the flow cytometric method to detect the total number of WBCs calculated by other methods may reflect filtration-induced changes in light-scattering properties of the WBCs. Although the method described does not accurately quantitate the total numbers of WBCs present in filtered RBCs, it may provide useful information on qualitative aspects of WBC subpopulations. PMID- 1755090 TI - Immune-mediated hemolysis associated with the administration of a radiographic contrast medium. AB - A female patient developed serious hemolysis in association with the injection of a radiographic contrast medium (RCM). Serologic investigation of her serum suggested complement-mediated hemolysis, induced by an RCM-dependent IgM antibody in her serum. The antibody was of high titer and low avidity. The antibody showed cross-reactions with related radiographic contrast media and reacted only with group I adult RBCs. PMID- 1755091 TI - Acute normovolemic hemodilution. PMID- 1755092 TI - Confidential unit exclusion: how should it be evaluated? PMID- 1755093 TI - The CUE debate (continued): on surrogate tests and surrogate endpoints. PMID- 1755094 TI - Potential accumulation of tri(n-butyl)phosphate in solvent-detergent virus inactivated plasma products. PMID- 1755095 TI - Infectious disease markers in directed donors in the Atlanta region. PMID- 1755096 TI - Controversial spindle cell tumors: an overview. PMID- 1755097 TI - Review and update: oncogenic osteomalacia-rickets. AB - Oncogenic or tumor-induced osteomalacia-rickets is a syndrome characterized by hypophosphatemia, renal phosphate wasting, and decreased serum 1,25 dihydroxyvitamin D3 levels. The tumors secrete a phosphaturic substance that causes total body phosphate depletion, leading to osteomalacia or rickets. Although the tumors are histologically polymorphous, personal review of 16 tumors documented to cause this syndrome revealed four morphologic patterns. The first contained 10 unique-appearing, mixed connective tissue tumors having variably prominent vessels, osteoclastlike giant cells, focal microcystic changes, dystrophic calcification, osseous metaplasia, and/or poorly developed cartilagelike areas. With one exception, all tumors of this group occurred in soft tissue and were benign. The single malignant tumor originated in bone, recurred locally, and metastasized to lung. The remaining tumors occurred in bone and showed benign clinical behavior. They resembled tumors known to occur in bone, that is osteoblastomalike (3 tumors), nonossifying fibromalike (2 tumors), and ossifying fibromalike (1 tumor). PMID- 1755098 TI - The enigmatic perineurial cell and its participation in tumors and in tumorlike entities. AB - The perineurial cells that make up the perineurium of peripheral nerve fascicles are characterized by distinct ultrastructural features, including non-branching thin cytoplasmic processes coated by an external lamina and joined at their ends by a tight junction, few organelles, actin and vimentin filaments, and numerous pinocytotic vesicles. Perineurial cells are immunoreactive for vimentin and epithelial membrane antigen (EMA) but not for the Schwann cell markers S-100 protein and Leu-7. The cytogenesis of the perineurium remains disputable, with morphologic, immunohistochemical, and experimental evidence supporting origin from the fibroblast, Schwann cell, and arachnoid cap cell. Ultrastructural studies more recently supported by immunolocalization of EMA have detected hyperplastic and neoplastic perineuriallike cells in a number of pseudoneoplastic lesions and true neoplasms, notably localized hypertrophic neuropathy, neurofibromas of various types, and perineurioma. PMID- 1755099 TI - Lipid-rich rhabdomyosarcoma--a potential source of diagnostic confusion. AB - Rhabdomyosarcoma is an often primitive tumor capable of diverse morphologic manifestations. The article describes three cases of childhood rhabdomyosarcoma in which a significant population of lipid-rich tumor cells was present. The lack of specificity and potentially confusing nature of this feature are discussed, and the ultrastructural diagnosis of rhabdomyosarcoma is briefly reviewed. PMID- 1755100 TI - Sarcomatoid renal cell carcinoma metastatic to the heart: report of a case. AB - An unusual case of metastatic sarcomatoid renal cell carcinoma is presented. Fifteen months after nephrectomy for a typical clear cell carcinoma, a 63-year old man presented with bilateral pleural effusions, cardiomegaly, and tamponade. A pericardial biopsy showed an anaplastic spindle cell tumor that was strongly keratin positive and showed desmosomes ultrastructurally. The patient died shortly thereafter, and the autopsy revealed massive tumor infiltration of the heart, pulmonary and adrenal metastases, and tumor nodules at the incision site of his nephrectomy. The differential diagnosis of sarcomatoid renal cell carcinoma is discussed. PMID- 1755101 TI - A study of spindle cell sarcomas showing myofibroblastic differentiation. AB - Five diagnostically problematic spindle cell sarcomas showing invasive character, cellular pleomorphism, and high mitotic rate were studied clinically and histopathologically by conventional light microscopy, immunohistochemistry, and transmission electron microscopy. They showed varied clinical courses, with two causing death within 5 years and three showing recurrent and metastatic behavior. All lacked a clearly defined line of differentiation by conventional light microscopy. By immunohistochemistry, all were positive for vimentin and alpha smooth muscle actin; in addition, one showed focal S-100 protein positivity, and one stained for desmin. All were cytokeratin negative. By electron microscopy, the great majority of spindle cells in all cases showed abundant rough endoplasmic reticulum and fine myofilaments with focal densities; collagen secretion granules were also found in all cases but in fewer cells. The fine structure and immunophenotype were considered consistent with myofibroblastic differentiation; these tumors, therefore, were designated as sarcomas of myofibroblasts or myofibrosarcomas. The suitability of the alternative diagnostic label of myofibroblastic or matrix-secreting variant of leiomyosarcoma is discussed. Comparisons with similar tumors documented in the literature are drawn. PMID- 1755102 TI - Primitive pelvic sarcoma resembling clear cell sarcoma of kidney. AB - Clear cell sarcoma of kidney (CCSK) is an aggressive childhood renal tumor of unknown histogenesis that has not been reported to occur outside the kidney. The article describes an extrarenal neoplasm arising in the pelvic soft tissues of a 13-year-old boy that was composed predominantly of uniform mesenchymal cells with optically clear cytoplasm supported by an arborizing network of small blood vessels, which was indistinguishable in appearance from CCSK. The electron microscopic findings, although nonspecific, were essentially identical to those of CCSK, with tumor cells displaying fine chromatin, electron-lucent cytoplasm, and intercellular collagen but no evidence of tissue-specific differentiation. Immunocytochemical studies showed positivity for vimentin but negative results for desmin, myoglobin, cytokeratin, epithelial membrane antigen, S-100 protein, neuron-specific enolase and factor VIII-related antigen. Tumor cells were also nonreactive with Ulex lectin. This unusual pelvic tumor and CCSK may both derive from primitive mesenchymal cells and may represent phenotypic but not necessarily histogenetic analogs. PMID- 1755103 TI - The diagnosis of thymoma: a review. AB - Thymoma is the most common tumor of the anterior-superior mediastinum, especially in middle-aged or older adults. Microscopically, thymomas can be differentiated from other tumors with which they can be confused by the finding of a mixed population of cells, including neoplastic thymic epithelial cells with numerous processes surrounding activated-appearing lymphocytes. Thymomas can be classified as benign or malignant, and the majority of those that are malignant appear cytologically benign and are locally invasive. Cytologically benign thymomas have been classified as being lymphocyte rich, epithelial cell rich, or spindle cell type. This classification has not been found to be prognostically useful. A new method classifies these tumors as being cortical, medullary, or mixed. This new classification appears to have prognostic significance. Malignant thymomas that are cytologically malignant are uncommon. Such tumors usually are squamous cell carcinomas. Other types include sarcomatoid carcinoma, clear cell carcinoma, basaloid carcinoma, and mucoepidermoid carcinoma. Because other tumors can occur in the anterior mediastinum, electron microscopy and/or immunocytochemistry is helpful in making the distinction. The differential features by ultrastructural and immunocytochemical analysis are reviewed. PMID- 1755104 TI - Lymphomas of the mediastinum. AB - The purpose of this clinicopathologic overview is to describe the types of lymphomas that present in the mediastinum. A comparison of the frequency of the different subtypes of lymphoma that are found in children and adults is provided. In general, immunohistochemistry and immunophenotyping studies are essential to the laboratory workup of neoplasms presenting in the mediastinum. An assessment of proliferative index in lymphoma is most helpful to determine tumor aggressiveness and patient prognosis. Electron microscopy is most helpful in the differential diagnosis of mediastinal neoplasms, where lymphomas may be distinguished from nonlymphomatous neoplasms using key ultrastructural features. The role of electron microscopy in the subclassification of lymphomas is mostly academic, with a few exceptions. The varied ultrastructural appearance of Hodgkin's cells and of different subtypes of non-Hodgkin's lymphoma is illustrated, using cases from our patient files. An ultrastructural study of lacunar cells in Hodgkin's disease provides evidence that the formation of lacunae may have a structural and/or physiologic basis. Mummified cells showing some of the features of a physiologic form of cell death, called apoptosis, are also described. PMID- 1755105 TI - Atypical tumor of the mediastinum: epithelioid hemangioendothelioma containing metaplastic bone and osteoclastlike giant cells. AB - A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma. PMID- 1755107 TI - Upper abdominal neoplasms: an introduction and selected references. AB - The organs in the upper half of the abdominal cavity can give rise to a highly heterogeneous collection of neoplasms that encompasses a broad spectrum of clinical features, light microscopic appearances, immunostaining properties, and fine structure. Because of the anatomic proximity of the viscera in this region, the differential diagnosis of an upper abdominal mass may include consideration of tumors that arise from the stomach, duodenum, liver, kidney, adrenal, and pancreas. There are many distinctive ultrastructural features among the various tumors that can be used effectively by the diagnostic electron microscopist, but it is also important to take into account the considerable overlap in fine structure that occurs among different tumors and among similar tumors from different organs. In the session on upper abdominal neoplasms, the electron microscopic characteristics of the common tumors of each viscus were reviewed before the presentation of individual case studies that incorporated original observations and illustrated some unusual entities. The selection of cases that follows is inevitably small and arbitrary, but the cases demonstrate the contribution that electron microscopy can make in the study of an upper abdominal mass and illustrate some of the similarities that can be encountered among tumors of different organs. PMID- 1755106 TI - Solitary fibrous tumor of the mediastinum. AB - A 62-year-old woman presented with an asymptomatic anterior mediastinal mass. Clinically considered to be a thymoma, the tumor was solid, firm, and composed of hypocellular dense collagen and cytologically bland, spindled fibroblastlike cells growing in a patternless pattern. There was no apparent connection to pleura or pericardium, yet the clinicopathologic features clearly fit with solitary fibrous tumor (SFT) of mediastinum. SFTs occur most commonly in pleura but have been reported in other locations, including the mediastinum, where aggressive behavior has been more common when these tumors are compared to those occurring in pleura. Although it is difficult to predict behavior for all cases of SFT occurring in the mediastinum by cytologic features alone, morphologic criteria for benign and malignant forms have been described. Roughly half the malignant forms will progress, yet the single most important indicator of clinical outcome is whether the tumor can be initially totally excised. PMID- 1755108 TI - Gastrointestinal stromal tumor of the duodenum: a case report. AB - The report describes a malignant gastrointestinal stromal tumor occurring in the duodenum in a 71-year-old woman. The neoplasm showed both epithelioid and spindle cell patterns by light microscopy. The ultrastructural features were diagnostic of nerve sheath origin. The tumor had numerous wrapping processes joined by junctions and surrounded by axons. No features of smooth muscle differentiation were identified. Immunocytochemistry was inconclusive. The differential diagnosis of such neoplasms is discussed. PMID- 1755109 TI - Retroperitoneal sarcoma with features suggestive of alveolar soft part sarcoma. AB - A 72-year-old man presented with a 15 x 12 x 5 cm cystic and necrotic tumor involving the superior region of the stomach and the retroperitoneum down to the transverse colon and extending laterally from the left lobe of the liver to the spleen without involving either organ. Light microscopy showed the tumor cells to be arranged in an organoid pattern. Immunocytochemistry showed a strong reaction for desmin and vimentin. Electron microscopy demonstrated features suggestive of an alveolar soft part sarcoma. PMID- 1755110 TI - Angiomyolipoma of the kidney with lymph node involvement. AB - A case of renal angiomyolipoma with regional lymph node involvement is added to 20 cases previously reported. This represents the 11th case reported in a non tuberous sclerosis patient. The electron microscopic features of the tumor are discussed and correlated with the light microscopic findings. PMID- 1755111 TI - Oncocytic adrenal cortical carcinoma. AB - A case of adrenal cortical carcinoma composed of mitochondria-rich cells is reported. The cells contained condensed zones and loose whorls of smooth endoplasmic reticulum. Crystalline matrical inclusions were present in some of the mitochondria, whereas others contained round, homogeneous, dense matrical inclusions. Flow cytometry revealed a hyperdiploid stem line with a DNA index of 1.3. PMID- 1755112 TI - Pheochromocytoma. AB - The cytoplasmic granules in an adrenal pheochromocytoma were predominantly ovoid with loose-fitting limiting membranes and eccentrically positioned dense cores. The occurrence of similar granules in a recurrent tumor involving the organ of Zuckerkandl in a second patient suggests that the latter tumor should be designated an extraadrenal pheochromocytoma. PMID- 1755113 TI - Hepatic angiomyolipoma with striated granules and positivity with melanoma- specific antibody (HMB-45): a report of two cases. AB - Angiomyolipoma occurs rarely in the liver, with only 25 previous cases being reported in the English literature. The article describes two additional cases, one of which was multicentric, with results of ultrastructural and immunocytochemical studies. Many of the tumor cells contained numerous electron dense granules, some with transverse striations like those found in melanosomes. Both tumors stained positively for S-100 protein and melanoma-specific antibody HMB-45. One case also expressed vimentin and neuron-specific enolase. Both were negative for cytokeratin, carcinoembryonic antigen, alpha-fetoprotein, desmin, muscle-specific actin, factor VIII antigen, and chromogranin. Comparison of our ultrastructural findings with those of classic renal angiomyolipoma raises the possibility that the melanosomelike structures may represent renin granules rather than melanosomes, although the latter are not excluded. Expression of HMB 45 in angiomyolipoma has important biologic and diagnostic implications, whether or not it reflects melanocytic differentiation. PMID- 1755114 TI - Biological calcium absorption edge imaging using monochromatic synchrotron radiation. AB - Soft X-ray contact absorption edge images of unfixed, unstained biological specimens were made using monochromatic synchrotron radiation. X-ray contact replicas of unfixed, hydrated biological specimens at the nitrogen absorption edge and above and below the CaLIII absorption edge were compared to comparative conventional morphological and elemental high-resolution imaging methods (scanning and transmission electron microscopy, TEM-histochemistry and TEM-X-ray microanalysis). Soft X-ray absorption edge images made above the calcium absorption edge clearly revealed morphological detail and identified regions ladened with calcium as verified by TEM histochemistry of identical spores. Similarly, nitrogen absorption edge images identified residual nitrogenous material in the spore resuspension medium, and non-viable spores with nitrogen loss due to protoplast disaggregation. PMID- 1755115 TI - [A method for modelling obstructive and nonobstructive hydroureteronephrosis (experimental research)]. AB - An experimental model of the upper urinary tract obstruction by means of cryosurgical liquid nitrogen destruction of an ureteral part has been created. The rabbit models provided obstructive ureterohydronephrosis in 100% of the animals, 56% of the dogs developed ureteral stricture in line with urodynamic alterations, the rest 44% had symptoms of nonobstructive ureterohydronephrosis as shown by excretory urography and dynamic nephroscintigraphy. One--three months after the destruction in dogs there were shifts in the intra-ureteral pressure and bioelectric activity, contractility of the fragments. The histological examination of the sections revealed necrosis at the destroyed site in the early postexposure period (2 weeks) followed by sclerosis and circulatory disturbances later on (3 months). The technique is simple, feasible in all laboratory animal species, highly reproducible. PMID- 1755116 TI - [The effect of extracorporeal piezoelectric lithotripsy on cardiac activity]. AB - To evaluate cardiac effects of shock waves, 40 patients with uroliths (10 subjects with and 30 without arrhythmia) were examined during their exposure to remote electropiezolithotripsy (Piezolith-2300 unit). Arterial pressure and ECG were registered before, during (upon 1500 and 3000 impulses) and after the session. Except a slight deceleration of the heart rate, no cardiac disorders significant clinically were reported. PMID- 1755117 TI - [Extracorporeal shockwave lithotripsy on the Sonolith-3000 apparatus]. AB - The authors observed 812 patients with nephrolithiasis who underwent 876 sessions of shock-wave lithotripsy on Sonolith-3000 lithotriptor supplied with an ultrasonic system of the stone localization. The size of nephroliths ranged from 0.7 to 4.2 cm. Large-size nephroliths required repeated sessions and pretreatment establishment of the stent. The procedure proceeded without anesthesia. Subsequent renal colic was reported in 126 (15.5%), an exacerbation of pyelonephritis in 45 (5.5%), subcapsular hematoma in 4 (0.5%) of the patients. 790 patients showed clinical response (97.3%), with a complete destruction of the stone in 446 (54.9%) and partial one in 344 (42.4%) cases. 27 subjects were treated in outpatient setting. According to the authors, lithotripsy is contraindicated in urinary tract obstruction below the stone, renal failure, chronic pyelonephritis in the active phase of inflammation, marked impairment of cardiac rhythm. PMID- 1755118 TI - [The significance of a congenital enterovirus infection in the pathogenesis of transient intrainfectious nephropathy and interstitial nephritis detected in children with influenza-like and acute respiratory diseases]. AB - The paper presents the data confirming the hypothesis on the involvement of the congenital enteroviral infection in etiology of chronic nephropathy manifesting in children in the presence of influenza-like and acute respiratory infections diseases. 100 relevant children were examined. Family history indicated a high risk of enteroviruses inheritance from mothers who were chronic carriers in 19 out of 20 children with pyelonephritis or interstitial nephritis (95%), in 17 out of 23 children with transitory nephropathy (73.9%) and 16 out of 57 patients without nephropathy (28.1%). Coxsackie enteroviruses (A and B) occurred in the urinary sediment in 82.3, 68.4, 29.5% of the patients from the groups under comparison, respectively. In children free of nephropathy the viruses manifested primarily in the seasons with the highest prevalence of the enteroviral diseases, in those with nephropathy Coxsackie viruses detection rate was not season related. Recognition of enteroviruses (Coxsackie B, as a rule) was significantly related to the risk of the transmission from the mother. Persistence of the viruses in the cells of the urinary system of children with congenital viral infection seems to run subclinically for a long time. Influenza and other acute respiratory diseases promoted activation of the endogenic infection which resulted in transitory nephropathy or interstitial nephritides. PMID- 1755119 TI - [Bacterial toxic shock in urological diseases]. AB - It is a review of present-day and historical aspects of bacterial toxic shock arising in urological setting. It is noted that conditions of its onset are changing, therapeutic approaches undergo revision, critical care facilities are updated. Among the causes of this complication the authors single out endoscopic procedures, transurethral interventions in the presence of infectious process, hospital infection, long stay at hospital. Forty-eight cases of bacterial toxic shock are reviewed in relation to classification, causes of development, treatment, bacteriological evaluation. PMID- 1755120 TI - [Immunity and the possibilities for immunomodulation in acute pyelonephritis]. AB - The paper presents evidence on dysfunction of natural killer cells and abnormal proliferative response of peripheral blood mononuclears to T- and B-cell mitogens (PHA, Phytolacca) in patients at varying stages of acute pyelonephritis. A number of immunomodulators (recombinant alpha 2-interferon, IL-2 and tactivin) produce different effects on natural killer activity and lymphocyte blast transformation in healthy donors and pyelonephritis patients. Immunotropic effects of immunopeptides depend on the drug dose, the response of various subpopulations of the immunocompetent cells being individual. It is suggested that immune system, natural killer activity in particular, plays an important part in pathogenesis of acute pyelonephritis. In vitro experiments demonstrate that there can be a positive clinical response to tactivin and recombinant alpha 2-interferon administered in doses activating the function of certain immunocompetent cells. PMID- 1755121 TI - [The hemostatic pursestring suture in adenomectomy of the prostate]. AB - It is a description of a new technique of putting a removable purse-string hemostatic stitch on the prostatic adenoma bed. Four stitches are made with a double catgut thread. The loop of the thread encircles the ureteral catheter introduced into the urethral tube. Upon tightening the purse, loose thread ends are connected with the urethral tube and fastened, the tube is tracted. Postoperative drop irrigation of the bladder with antiseptic drugs proceeds through the ureteral catheter. The purse-string suture is taken out when the catheter is removed from the urethral drainage at postoperative hour 20-24. The bladder is sutured tightly using double-row buried purse-string gut stitches. A total of 143 patients underwent surgery according to the technique of whom 70% had aggravating chronic cysto-pyelonephritis, 17.5% suffered from urolithiasis, 72% from cardiac diseases and 30% of respiratory disorders. 28% of the patients combined prostatic adenoma with chronic prostatis. 38 patients (26.5%) needed blood transfusions. Mean stay in hospital after one-stage adenomectomy made up 16.4 days at stage I-II of the disease, after delayed adenomectomy 19 days, after two-stage adenomectomy 21.8 days. Two patients died (1.37%). PMID- 1755122 TI - [Gunshot wounds of the kidneys]. AB - Upon the analysis of the treatment for gunshot wounds of the kidneys (n = 113), it is concluded that in the majority of cases such wounds (91.1%) were associated with additional injuries of other viscera, this complicating the diagnosis and treatment, aggravating the prognosis. At admission, 81.4% of the wounded were in shock, with signs of hemorrhage. Serious condition of the patients dictated urgent surgery imposing limitations on diagnostic examinations, e.g. intravenous urography was performed in 5.3% of the cases only. Therefore, preoperative detection of renal injuries was far from universal. (55.6%). Hematuria prompted renal damage in 74% of cases. 92% of the wounded underwent surgery, in 62.8% of them it was nephrectomy. Serious combined wounds terminated in lethal outcomes in 50.4% of cases, though renal damage was responsible for 4% of deaths only. Introduction of up-to-date methods of examination (CT, ultrasonography, excretory urography) may raise the frequency of the kidney-preserving operations and favourable outcomes. PMID- 1755124 TI - [The biochemical characteristics of the sperm in patients with varicocele]. AB - Biochemical evaluation of ejaculates from males suffering from varicocele provided evidence on reduced fertility of their gametes mainly due to these cells hypoactivity consequent to insufficient generation of energy supplied during fructose oxidation. Lowered intensity of fructose oxidation in gamete mitochondria led to lactate accumulation in line with ultrastructural derangement of the flagellum and mitochondria with inhibition of dehydrogenases activity. Morphological abnormalities of the gametes are attributed to impaired gametogenesis in reproductive system of men with varicocele. PMID- 1755123 TI - [The surgical treatment of urinary incontinence in children]. AB - The paper reports examination, treatment and follow-up data on 8 children aged 4 13 suffering from total enuresis, who failed previous conservative or operative treatment. Upon examination enuresis was attributed to trauma or malformations of the neck of the urinary bladder (NUB) or urethra (in 2 and 6 patients, respectively). Out of the latter, NUB congenital defect was in 4, total epispadia in 1, spina bifida in 1 patient. Urodynamic studies showed the absence of detrusor-sphincter dyssynergia and confirmed organic nature of NUB lesion. Six children underwent NUB electromyography which recorded no uniform, preformed complexes with adequate voltage. All the children were operated on: NUB reconstruction according to Davis, bilateral uretero-cystostomy according to Coen. An immediate postoperative response was seen in 7 children who were able to retain urine for 40 min-2.5 hours. Long-term response (6 months-3 years) was achieved in 7 children who recovered normal uresis. Total enuresis persisted in 1 patient with spina bifida. 2.5-3 years after the treatment the bladder capacity increased in spite of its resection by 1/3. PMID- 1755125 TI - [Chromosomal anomalies in men with infertility]. AB - Out of 35 sterile males with impaired spermatogenesis two patients had "XX-male" syndrome and one patient had Y-chromosome deprived of a long arm. The three patients presented with similar clinical manifestations: short height, non manifest malformations, impaired spermatogenesis, sterility. PMID- 1755126 TI - [Immunochemical tests in the diagnosis of diseases of the male reproductive system]. AB - Immunochemical tests were employed to measure proteins (acid phosphatase, prostatic beta-globulin, endometrial alpha-2-globulin, lactoferrin, carcinoembryonal antigen) in spermatic plasma and prostatic fluid from healthy subjects and patients with prostatic adenoma, cancer, chronic inflammation, defects of spermatogenesis. It was found that the overall concentration of acid phosphatase and prostatic beta-globulin may serve a diagnostic criteria to differentiate prostatic adenoma from cancer as in 93% of prostatic cancer this parameter did not exceed 400 micrograms/ml whereas in 75% of adenomas it was above 1200 micrograms/ml. Activity of chronic prostatitis can be assessed from lactoferrin test. The level of the organ-specific antigens (acid phosphatase and prostatic beta-globulin) and lactoferrin correlated with the severity of spermatogenesis disorders. PMID- 1755127 TI - [Buried suture of the bladder in the surgical treatment of urethral stricture]. AB - Surgical treatment for posttraumatic urethral stricture was carried out in 316 patients: tunneling in 42, Marion-Khol'tsov [correction of Kholtrov] operation with circular drainage in 185, tight suture of the bladder with transurethral drain using double-opening tube in 86 cases. Complications emerged in 28 patients. The best short- and long-term outcomes were obtained in the group subjected to tight suturing. PMID- 1755128 TI - [The prevention and treatment of posttraumatic strictures of the posterior urethra in patients with pelvic bone fractures]. AB - Urethral strictures resultant from hip fractures were examined and treated in 140 patients admitted to hospital with multiple attendant traumas: rupture of the bladder and abdominal organs, rib and limb fractures, renal injuries. All of them underwent epicystostomy followed in 3--4 months by urethroplasty. Drainage of the bladder and paracystic fat was passive in 38 and active in 102 patients. Passive drainage, common in urological practice, failed to yield satisfactory results because of deficient urine outflow from the bladder and gave rise to various complications: phlegmons, femoral osteomyelitis, pyelonephritis, urosepsis. Fourteen patients developed urinary fistulas, four subjects had a large postoperative hernia involving the bladder. The adverse effects made urethroplasty problematic. With active drainage, the bladder and paracystic fat were continuously irrigated with drug solutions siphoned off from a jar into a dropper obtained from a disposable hemotransfusion system. Patients on active drainage avoided complications, 47 of them were successfully operated on the urethra, in 55 urethral competence recovered without surgical interventions. PMID- 1755129 TI - [Postinflammatory strictures of the urethral canal in women]. AB - The paper is concerned with one of the important problems of current urology- inflammation-induced strictures of the female urethra, covers questions of its etiology, pathogenesis, clinical patterns, diagnosis and treatment. It is emphasized that the strictures take the form of paraurethral fibrosis and should be managed individually. Clinicomorphological parallels are outlined. Indications to conservative and surgical treatment are specified. PMID- 1755130 TI - [Nephrectomy with resection of the pancreas and cupula of the diaphragm and splenectomy for cancer of the left kidney]. PMID- 1755131 TI - [A case of the good effect of low doses of erythropoietin]. PMID- 1755132 TI - [A case of a vesicouterine fistula]. PMID- 1755133 TI - [Electroacupuncture and laser puncture in the early postoperative period of urological patients]. AB - To provide an objective assessment of the analgetic effect obtained at electric or laser acupuncture early after operative treatment of 117 uronephrological patients, the study was performed of a general vegetative and psychoneurological responses and blood levels of some hormones. There were positive effects on psychoemotional postoperative stress, pain impulses from the wound reflected by higher pain thresholds and lowered levels of contrainsular hormones against higher insulin and C-peptide concentrations. These changes were dependent on a nociception degree and agreed with the analgetic action of the reflex anesthesia modalities. PMID- 1755134 TI - Spectrum of renal vascular malformation. AB - In summary, renal AVMs are rare. The possibility of these lesions should be raised in cases of hematuria of unknown etiology, prolonged hematuria following trauma or needle biopsy, unexplained congestive heart failure or abdominal/flank bruit, or hypertension after renal trauma. Selective renal arteriography is the study of choice for establishing the diagnosis, the hallmark being demonstration of an abnormal arterial communication with a vein. The goal of management should be maximum preservation of renal parenchyma. Observation with follow-up is indicated for asymptomatic AVMs. PMID- 1755135 TI - Intraoperative anaphylactic reaction due to latex hypersensitivity. AB - Severe anaphylactic reaction secondary to latex allergy has lately been recognized and reported especially in individuals with spina bifida. We report a case of severe intraoperative anaphylactic reaction due to latex allergy. Preoperative testing for latex allergy may be helpful in determining latex allergy. We suggest a preoperative management protocol for patients who are thought to have latex allergy. An increased awareness to latex allergy will help avoid this potentially catastrophic event. PMID- 1755136 TI - Flow cytometric analysis of cellular deoxyribonucleic acid content of nine renal oncocytomas. AB - The cellular deoxyribonucleic acid content of formalin-fixed, paraffin-embedded tissue from nine renal oncocytomas was determined using an Epics-C flow cytometer. The tissues were all from surgical specimens, and all neoplasms met stringent light and electron microscopic criteria for the diagnosis of oncocytoma. Thirteen samples of pure tumor, 5 of tumor and normal kidney, and 3 of normal kidney alone were analyzed. All oncocytomas had single, sharp G1 peaks with no evidence of aneuploidy, and this peak was similar to that of normal renal parenchyma. This was true even for three oncocytomas that had multiple major chromosomal anomalies on karyotyping. These data support the concept that renal oncocytomas are euploid neoplasms, consistent with their benign biologic behavior. The apparent discrepancy between the results of flow cytometry and karyotyping is discussed. PMID- 1755137 TI - Fibrin glue for partial nephrectomy. AB - Fibrin glue, a mixture of concentrated autologous fibrinogen and bovine-derived thrombin, was used to achieve hemostasis during 7 partial nephrectomies. After transected vessels were suture ligated, topically applied fibrin glue filled all renal defects with an adherent clot that resulted in immediate hemostasis. There was no case of delayed hematoma or abscess formation, and no complications were referrable to the use of fibrin glue. Although fibrin glue is no substitute for early vascular control and careful surgical technique, its ability to stop venous oozing from the cut surface of renal parenchymal tissue dramatically facilitates hemostatic control. PMID- 1755138 TI - Possible hypothalamic impotence. Male counterpart to hypothalamic amenorrhea? AB - Twenty-one men with erectile complaints who were found to have a low level of serum testosterone without a reciprocal elevation of the serum levels of luteinizing hormone were evaluated to identify whether the defect was of hypothalamic or of pituitary origin. Patients underwent a luteinizing hormone (LH)-follicle-stimulating hormone (FSH)-releasing hormone stimulation test that showed a normal but sluggish increase in LH and FSH levels, thus ruling out a pituitary defect and suggesting a suprapituitary abnormality. This was confirmed when, in response to clomiphene, patients had a normal increase in gonadotropin and testosterone levels. Although the basal as well as clomiphene and gonadotropin releasing hormone-stimulated levels of total testosterone and gonadotropins were identical in men less than and more than fifty years old, the elevation of free testosterone levels in response to clomiphene was higher in patients younger than fifty. This suggested that although the primary abnormality found in these patients is altered secretion of gonadotropin hormone-releasing hormone from the hypothalamus, an age-related decline in the responsivity of Leydig cells to LH may make it more manifest in older patients. Elevation of testosterone levels from a subnormal to a normal range in response to clomiphene administered for seven days suggests that the defect is functional and reversible and that the drug may be useful in treatment of sexual dysfunction in this group of patients. PMID- 1755139 TI - Vacuum constriction devices and the clinical urologist: an informed selection. AB - The U.S. Food and Drug Administration (FDA) lists vacuum constriction devices (VCD) as safe, nonsurgical therapy for erectile dysfunction. Our study compared the responses of 30 male (10 novice and 20 regular) VCD users of seven commercially available systems (Mentor Response, Mentor-Touch, Mentor-Piston, Dacomed Catalyst, Mission VED, Osbon ErecAid, and Pos-T-Vac). Variables evaluated included simplicity of instruction, ease of use, cost, instructional value of videotape, company follow-up, presence of a pressure-limitation gauge, and length of warranty. The results from our study show (1) 100 percent reported an additional cost to be of minor importance in determining choice of device, (2) 80 percent of novice and 95 percent of regular users stated the instructional videotape was essential, (3) 95 percent of the participants desired a twenty-four hour hot-line, (4) 40 percent of novice users but only 25 percent of regular users wanted personalized company follow-up, (5) 100 percent of novice users preferred single-handed devices, while regulars showed no preference. (6) Regular users scored Mentor Response, Osbon ErecAid, and Mentor-Piston highest regarding ease of use. While the vacuum constriction devices are conceptually similar, there are subtle operational distinctions between the different brands. The clinical urologist should be aware of these nuances. PMID- 1755140 TI - Does the Kaufman prosthesis still have a place? Review of thirteen years' experience. AB - The cases of 57 patients who underwent implantation of a Kaufman prosthesis for urinary incontinence at this center are reviewed. All except one of the patients were incontinent following prostatic surgery. Although many of the patients required revision or adjustments after the initial implantation, 55 percent of the cases eventually had a satisfactory outcome. Patients rendered incontinent after retropubic prostatectomy had a higher success rate with the Kaufman prosthesis than patients after other types of prostatectomy. This simple and relatively inexpensive device can still play a useful role in the treatment of patients with mild and moderate stress incontinence following prostatectomy. PMID- 1755141 TI - Pelvic physiotherapy in genuine stress incontinence. AB - In a prospective cohort study, the effect of pelvic physiotherapy on genuine stress incontinence, factors that influence therapy outcome, and patients' attitudes toward physiotherapy were studied. The study group consisted of 52 ambulatory and mentally fit Caucasian women (mean age, 53 years), suffering from genuine stress incontinence and who had no contraindications for surgery. They had physiotherapy twice weekly for ten weeks. The aim of physiotherapy was strengthening the pelvic floor muscles under control of digital vaginal palpation. Therapy outcome was assessed by a questionnaire and by the patients' self-monitoring urinary diary recording pad changes (52) and number of leakage episodes (35) before treatment and at end of therapy. The questionnaire also served to determine how patients appreciated physiotherapy. Physiotherapy had a low cure rate (+/- 25%) but a high improvement rate causing a decreased demand for surgery. At follow-up (mean 14 months) its beneficial effect was maintained. To date, only 10 patients (19%) have undergone surgery. Severity of symptoms was the only limiting factor. We conclude that every woman with urinary stress incontinence is a potential candidate for physiotherapy but surgical treatment as an option must remain open. Overall, physiotherapy was well accepted since episodes of urinary incontinence were less frequent and therefore bearable; however, changes in patients' behavior play a role. PMID- 1755142 TI - Kidney stone formed around refluxed surgical staple and removed by transureteral endoscopic manipulation. AB - We present a case of a kidney stone that developed around a surgical staple which refluxed up to the kidney following a Bricker urinary diversion and bilateral ureteroileal anastomosis. A GIA stapler had been utilized to construct the ileal conduit. The stone was retrieved by means of flexible ureterorenoscopy through the ileal conduit. To our knowledge, this is the first report of such a complication following construction of an ileal conduit with a stapling device. PMID- 1755143 TI - Relationship of voiding dysfunction to urinary tract infection and vesicoureteral reflux in children. AB - A total of 109 children were evaluated for urinary tract infections or for voiding dysfunction without infections. The relationship of voiding dysfunction to urinary infection and vesicoureteral reflux was then examined in girls. The number of males studied was too small for statistical analysis. While 40.6 percent of females with infections had voiding dysfunction, in 66.6 percent of those females having voiding dysfunction infections also developed. Voiding dysfunction was noted in 33.3 percent of females with reflux, probably due to the strong association of reflux and infections. However, all of females with voiding dysfunction, only 20.6 percent also had reflux. These findings were statistically significant (p = 0.01) and suggest that voiding dysfunction is common in girls with infections, perhaps even predisposing to the development of infections. However, voiding dysfunction in this population did not predispose to reflux. PMID- 1755144 TI - Nephrogenic adenoma with bladder exstrophy and immunosuppression. AB - Nephrogenic adenoma, an unusual proliferative lesion, often occurs in association with chronic inflammation of the bladder and is rarely found in children. Two cases are reported, one occurring in a young child born with bladder exstrophy, and one in a young female, with both interstitial cystitis and chronic use of immunosuppressive therapy. We believe these are the first case reports of nephrogenic adenoma occurring in this specific clinical setting. PMID- 1755145 TI - Occurrence of congenital abnormalities of kidney and urinary tract in 13,775 autopsies. AB - Records of 13,775 consecutive autopsies were reviewed to determine the incidence of renal and urinary tract abnormalities. A total of 636 abnormalities were found in 427 autopsies, with an overall frequency of 4.6 percent and 9.5 percent in males under eighteen years old. The kidney was involved in 45.1 percent, ureters 29.1 percent, renal vessels 12.4 percent, urethra 5.3 percent, bladder 4.8 percent, and fistulas 3.3 percent. We conclude: (1) Although it is difficult to assess accurate incidence rates of renal and urinary tract abnormalities, this study notes the frequency of these abnormalities in autopsies. (2) The markedly higher incidence in the younger age group indicates the high mortality of many of these anomalies. (3) Over 85 percent of abnormalities are in the upper urinary tract, which are more likely to produce end-stage renal disease and a higher mortality. (4) These observations indicate the importance of further research to establish methodology for early detection of congenital abnormalities of the kidney and urinary tract. PMID- 1755146 TI - Gallium nitrate in advanced bladder carcinoma: Southwest Oncology Group study. AB - Gallium nitrate is a heavy metal anticancer agent that has demonstrated widespread activity in a number of phase I studies. This phase II study employed a starting dose of 700 mg/m2 IV every two weeks in patients with advanced bladder carcinoma. Significant nephrotoxicity observed in 4 of the first 10 patients required extending the time between cycles to three weeks in the remaining 24 patients. One complete response and six partial responses were achieved. Nephrotoxicity was the major dose-limiting toxicity. Gastrointestinal toxicity and myelosuppression were minimal. Gallium nitrate appears to be an active agent in advanced carcinoma of the bladder. Further clinical trials with this agent are warranted. PMID- 1755147 TI - Duraphase penile prosthesis dorsal approach using local anesthesia. PMID- 1755148 TI - Chronic renal failure secondary to post-hysterectomy vaginal prolapse. AB - The first case of posthysterectomy vaginal prolapse and associated chronic renal failure requiring hemodialysis is presented. A review of the literature on vaginal prolapse and the mechanism and physiology of chronic renal obstruction in this setting is reviewed. PMID- 1755149 TI - Renal cell carcinoma with solitary metachronous contralateral adrenal metastasis. Experience with 2 cases and review of the literature. AB - We report on 2 cases of renal cell carcinoma with solitary metachronous contralateral adrenal metastasis occurring up to four years after radical nephrectomy. Both patients were treated with adrenalectomy and steroid replacement. One patient died with distant metastases twenty-eight months after adrenalectomy and the other is alive with no evidence of disease four years postoperatively. Such a presentation of hypernephroma is rare, with only 1 such case having been found in the literature. PMID- 1755150 TI - Adenomatoid tumor of epididymis simulating benign cyst on scrotal ultrasound. PMID- 1755151 TI - Renal cell carcinoma in avascular cyst. PMID- 1755152 TI - Prostatic tissue levels of ofloxacin. AB - The prostatic tissue levels of ofloxacin were determined in 20 patients undergoing transurethral resection of the prostate. Ofloxacin was administered in two separate dosages of 300 mg PO from twenty-two to two hours preoperatively. The ofloxacin plasma concentrations ranged from 3.73 to 1.85 micrograms/mL at the time of surgery, and the tissue concentrations ranged from 4.55 to 1.94 micrograms/mL. The ofloxacin tissue/plasma ratios ranged from 0.9 to 1.2. These findings indicate that ofloxacin may be useful in prophylaxis prior to transurethral prostatic surgery and also in the treatment of bacterial prostatitis. PMID- 1755153 TI - Malignant juxtadrenal schwannoma. AB - We believe we report the first case of malignant juxtadrenal schwannoma. This rare tumor was discovered incidentally in a patient who presented with fever, mental confusion, weight loss, leukocytosis, and elevated erythrocyte sedimentation rate. Preoperative radiographic and endocrine evaluations were suggestive of a nonfunctioning adrenal tumor. Its suprarenal location was unequivocally demonstrated by CT scan, sonography, angiography, and magnetic resonance imaging studies. Angiography revealed that the tumor derived its blood supply from the adrenal and renal vessels. The final diagnosis and its juxtadrenal origin was confirmed by histologic and immunohistochemical studies. A review of the literature on retroperitoneal schwannoma is included. PMID- 1755155 TI - Femoral neuropathy complicating urologic surgery. PMID- 1755154 TI - Effect of decentralization and partial outflow obstruction on cholinergic receptors in urinary bladder of rabbit. AB - In this study we have examined the cholinergic receptor density on the detrusor smooth muscle from rabbits with decentralized autonomous bladders and animals with partial outlet obstructions using (3H) quinuclidinyl benzilate ([3H] QNB). Decentralized spinal bladders were obtained from rabbits made paraplegic by a twenty-minute ischemic lesion to the lumbar and sacral spinal cord. Bladder tissues from these rabbits were studied from one, two, five, and nine-day intervals after the ischemic lesion. The affinity of the muscarinic binding sites for (3H) QNB was virtually unchanged at any of the time intervals, while the total Bmax was significantly reduced at one and two days but recovered to normal levels by the fifth and ninth day after the ischemic lesion, provided the bladder had been effectively manually emptied on a regular basis. In a parallel study animals with a partial outlet obstruction or spinal animals with marked bladder distention at the time of sacrifice showed that the cholinergic receptor density was significantly reduced. PMID- 1755156 TI - Urinary cytology: simple screening procedure for lymphadenopathy. PMID- 1755157 TI - [Effectiveness of laser treatment of narrow-angle glaucoma]. AB - Forty-eight patients with narrow-angle glaucoma were treated with M-900 argon laser (Coherent Radiation, USA). Reduction of intraocular pressure as low as 20 +/- 1.82 mm Hg on an average was achieved. Fluid discharge efficacy coefficient has improved. The authors claim that laser cyclotrabeculospasis a sufficiently effective method for the treatment of primary narrow-angle glaucoma. PMID- 1755158 TI - [A theory on the role of immunologic factors in the pathogenesis of primary glaucoma]. AB - Basing on the literature data and their own clinical, immunomorphologic, and immunochemical findings in glaucoma patients and normal subjects, the authors suggest a concept on the immune factor contribution to the pathogenesis of primary open-angle glaucoma. According to the scheme they suggest, of primary importance in the development of autoimmune reactions in glaucoma are the following factors: changed antigenic specificity of the drainage zone tissues, resultant from involution processes; impaired immune homeostasis, effects of various internal and environmental factors. The pathogenetic role of autoimmune reactions and immunity system regulatory mechanism disorders is explained. PMID- 1755160 TI - [Treatment of central ruptures of the retina]. PMID- 1755159 TI - [Effect of lipoic acid on tyrosine metabolism in patients with open-angle glaucoma]. AB - Lipoic acid effects on tyrosine metabolism and ocular hydrodynamics were examined in patients with primary open-angle glaucoma. Glaucoma patients not administered the drug and patients with ocular hypertension made up two reference groups. In the majority of glaucoma patients administration of lipoic acid did not result in improvement of tyrosine metabolism, whereas hydrodynamic parameters somewhat increased. Tyrosine metabolism normalized in the patients administered lipoic acid in complex with tyrosine catabolism cofactors (pyridoxal phosphate, ascorbic acid, iron ions). The studied parameters improved in ocular hypertension patients administered lipoic acid. The authors' findings and the literature data permit recommending lipoic acid in complex with vitamins B1, B2, B5 (PP), B6 (pyridoxal phosphate), C to glaucoma patients. Judging from the reaction to lipoic acid administration, tyrosine catabolism enzyme activities in glaucoma patients are related to a peculiar sensitization of the body. PMID- 1755161 TI - [Refraction ring-shaped tunnel keratoplasty in the correction of high-degree myopia]. AB - A new method has been developed for diminishing the myopic eye refraction: refraction ring-like tunnel keratoplasty. The technique is simple, virtually atraumatic, and highly effective. It has been introduced in clinical practice. The method consists in placing a ring-shaped collagen thread ++para-centrally in the surface layers of the cornea. Experimental studies of refraction ring-like tunnel keratoplasty included staining the sections with hematoxylin and eosin and Kampos' silver impregnation. Changes in the transplant shape and the host cornea, as well as the terms of their innervation were studied in histologic sections. The results of 32 surgeries are analyzed. Essential reduction of the refraction in the myopic eye--12.0-15.0 diopters, vision acuity improvement in the operated on eyes without correction (in cases without astigmatism), and a stable refraction effect were achieved. The authors recommend the new method of refraction keratoplasty for practice. PMID- 1755162 TI - [Clinical characteristics and results of microsurgical treatment of bilateral congenital cataracts associated with microphthalmos]. AB - Examinations of 146 children (267 eyes) with bilateral congenital cataracts and microphthalmia have revealed complete microphthalmia in 66 percent of cases, anterior microphthalmia (microcornea) in 34 percent, and various solitary and multiple abnormalities of the anterior section of the eye: microcornea, ectopic pupil, no pupil, a pupil membrane, iridal hypoplasia and aplasia, iridocorneal adhesions, etc. A total of 224 cataract extractions by the aspiration irrigation method were carried out with the use of microsurgical equipment. In cases with abnormalities of the anterior segment of the eye and with some abnormalities of the posterior segment cataract extraction was coupled with reconstructive surgery (creation and center adjustment of the pupil, adhesion dissection, removal of the pupil and hyaline membranes, etc.). Good effect was achieved in 98.2 percent of cases, vision acuity improved in 9.2 percent of cases. Vision acuity of 0.05-0.3 diopters (with eyeglass correction) was achieved in 74.1 percent of cases, that of 0.1-0.3 diopters in 29.9 percent. Anatomical and functional inadequacy of the eye, abnormalities of the fundus oculi, and deprivation amblyopia are responsible for poor functional results. The results evidence a possibility of rehabilitation of children with grave congenital conditions, bilateral congenital cataracts with microphthalmia. PMID- 1755163 TI - [Extra-scleral balloon catheterization. Report 3. New ways of its use--prevention of hypotonia and intraocular hemorrhages in vitreo- retinal surgery]. AB - Hypotonia and ex vacuo hemorrhages are the most grave complications of vitreoretinal surgery; the known methods of their prevention are altogether inadequate. The authors have developed extra-scleral ballooning (ESB) methods that improve the efficacy of surgery and reduce the rate and severity of complications in subretinal fluid draining during surgery for detachment of the retina and in arresting intraocular hemorrhages during closed vitrectomy. ESB application helped elevate intraocular pressure in the patients with drastic hypotonia, permitting a reliable and easy-to-perform monitoring of intraocular pressure over the course of surgery. This was conducive to complete evacuation of subretinal fluid, thus preventing the development of hypotonia and its complications, as well as to a rapid arrest of intraocular hemorrhage due to rapid elevation of intraocular pressure up to the values essential for the bleeding vessel collapse. Surgical methods are described and their results analyzed in 65 cases. The developed ESB methods for the prevention of hypotonia and intraocular hemorrhages in vitreoretinal surgery are effective, low traumatic, and may be recommended as alternative ones. PMID- 1755164 TI - [Monocular diplopia]. AB - Monocular diplopia is a condition when a single object is seen double with one of the eyes. Fifty-seven cases of this condition are described. Traditional ophthalmologic methods, as well as examinations of the optic system aberrations and determination of diplopia type with a cross pattern were employed in examinations of the patients. A classification of monocular diplopia has been developed, including (1) refraction, (2) aberration, (3) pupillary, (4) retinal, and (5) neurogenic diplopia. Methods of examining this patient population are described and recommendations on the treatment of this condition presented. PMID- 1755165 TI - [Immunologic disorders in young patients with retinal vein thrombosis]. AB - Immunologic shifts in 53 patients with retinal vein thrombosis, aged 20 to 41, were under study. Present-day immunologic methods were employed to investigate the status of the humoral and cellular immunity and define the infection rate. The results were assessed functionally and immunologically. The authors have revealed the contribution of infection to the development of retinal vein thrombosis in young patients, analyzed for the first time the immunity status of such patients, detected the signs of humoral immunodeficiency are senting as gammapathies and impaired complex formation, showed the relationship between thromboses and genetic predisposition and the role of the erythrocytic phenotype in the development of a cyst-like edema; this permitted them develop recommendations on the disease source and outcome prediction and on the choice of drugs. PMID- 1755166 TI - [Immunity status in patients with injuries and diseases of the cornea]. AB - Clinical and immunologic examinations of 97 patients with leukoma after corneal injuries and diseases have shown that immunity disorders are present in leukoma of whatever origin. The authors claim that preoperative treatment of the patients before keratoplasty should include study of the background immunologic tests, the most informative of these being the leukocyte migration inhibition test with the corneal antigen. PMID- 1755167 TI - [Problems of scientific evaluation of the quality of the treatment of eye diseases]. AB - Analyzing the trends in the development of ophthalmology development in this country and abroad, the author comes to a conclusion that the market economy may result in deterioration of the quality of treatment. Development of exitology, a science of the treatment outcomes, may inhibit the development of such trends; this science is supposed to assess the known therapeutic methods basing not only on their authors' recommendations, but mainly on the basis of sociologic studies with the patients participating in these studies. PMID- 1755168 TI - [A phototopographic method of measuring the thickness of the cornea]. AB - This method is based on asymmetric growth and distension of the cornea in various directions. One has just to ascertain the visual line projection site on the corneal surface and to measure the corneal thickness in but two points, in the centre and lower, near the limbus; then the thickness of the cornea at any site of the cornea may be calculated, for the cornea is the thinnest at sites where the limbus is the furthest from the centre. The accuracy of this method is not inferior to that of the known optic method. PMID- 1755169 TI - [Evaluation of the visual evoked potentials in relation to the type of visual stimulation]. AB - A classification of visual evoked potentials (VEP) in children and adults in response to various types of vision stimulation has been developed. Four major signs underlie this classification: (1) stimulation time frequency; (2) stimulation type; (3) mode of producing the visuals stimulus; (4) mono- or binocular presentation of the stimulus. One more sign can be added to classification: significant parameters of stimulation. Basing on this classification, the author describes the major VEP modalities and gives recommendations on the practical employment of these modalities. PMID- 1755170 TI - [Visual evoked potentials in chessboard pattern reversion in children with optic neuritis]. AB - Visual evoked potentials (VEP) to chess pattern reversion were studied in 17 children with optic neurites during the acute stage and in the course of convalescence 1-2 months and 1-3 years after the disease onset. Coarse VEP changes were detected in the patients during the acute stage of optic neuritis. A positive time course of VEP was followed up in late periods after the acute attack of the disease. Despite normalization of vision acuity, no complete restoration of VEP to small-cell chess patterns was seen. The findings evidence that studies of VEP to chess pattern reversion should be carried out to detect subclinical involvement of the optic nerve and to timely diagnose optic neuritis in children. PMID- 1755171 TI - [Use of phacolin in patients with allergic reaction to anti-cataract eye drops]. AB - Allergic reaction to ++anti-cataract eye drops was confirmed in 11.1-34.8 percent of patients with these drops intolerance. Administration of phacolin in capsules to such patients helped eliminate the local allergic reactions. Phacolin had a reparative therapeutic effect in patients with metabolic involvement of the cornea (postherpetic, dystrophic, and other ones). None of the seventy-two patients treated with phacolin, twenty of them were treated with the drug for 2 to 5 years, complained of the drug intolerance. PMID- 1755172 TI - [Value of a scleral flap in the surgical treatment of glaucoma]. PMID- 1755173 TI - [1991 review of memorable dates in the history of ophthalmology]. PMID- 1755174 TI - [A method of increasing the effectiveness of anti-glaucoma operations]. AB - The authors have proved the possibility to prevent cicatrization between scleral laminae after antiglaucoma surgery in 16 rat experiments. They analyze late and remote results of 341 surgeries for open-angle glaucoma, 52 of these traditional trabeculectomies and 289 trabeculectomies with placing hemostatic viscose under the scleral flap. The results evidence the efficacy of viscose application: the incidence of complications early after surgery and in the late periods was essentially reduced and a more stable hypotensive effect achieved. The method is simple and available. PMID- 1755175 TI - [Results of endonasal intubation of the nasolacrimal duct in children with congenital dacryocystitis]. AB - Results of endonasal catheterization of the naso-lacrimal canal of 74 children with congenital dacryocystitis (bilateral problem in 10 of them) are presented. Prior to this manipulation, the patients were exposed to contrast X-ray study of the lacrimal sac for diagnostic purposes. Retrograde catheterization as a method for treating congenital dacryocystitis was very good in 97.3% children of up to 2 years old, 50% children of up to 3 years old, and 33.3% children between 3-4 years old. The patency of the naso-lacrimal canal also recovered in an 8-year-old child. All this gives evidence that, irrespective of children's age, retrograde catheterization should be applied to treat congenital dacryocystitis. After the patency of the naso-lacrimal canal was restored, the external fistula of the lacrimal sac was cauterized with 7% solution of trichloroacetic acid. PMID- 1755176 TI - [Use of semiconductor laser in the treatment of various inflammatory ORL diseases]. PMID- 1755177 TI - [Comparative study of alginate coating and charcoal sorbent in the treatment of wounds in otorhinolaryngology]. PMID- 1755178 TI - [Effectiveness of human leukocytic interferon in children with papillomatosis of the larynx, trachea and bronchi]. AB - The results of interferon therapy of 32 children with severe forms of laryngeal, tracheal, and bronchial papillomatosis are very encouraging. Clinical recovery (no relapses during 3 years or longer) was observed in 8 patients, improvement (no relapses during less than 3 years or 2-3-fold prolongation of no-relapse periods) was seen in 12 patients, no changes were recorded in 10 children; data on 2 other patients were too limited or lacking at all. The efficacy of interferon therapy of airways papillomatosis can be further increased, if doses are selected on an individual basis. PMID- 1755179 TI - [Treatment of recurrences of malignant tumors of the maxilla]. PMID- 1755180 TI - [Disorders of physiological parameters of the body (lipid peroxidation and microcirculation) after naso-orbital injuries and the methods of their correction]. AB - A naso-orbital injury is often associated with a craniocerebral injury due to the close anatomical localization of the facial and cerebral compartments of the skull. Patients with such injuries showed enhancement of free-radical lipid oxidation and microcirculation disorders. They were controlled by traditional therapeutic methods in combination with antioxidants of direct and indirect action (ascorbic acid, flacumin, alpha-tocopherol acetate, pentoxifylline ) that were given in standard doses. Improvement of microcirculation and decrease of free-radical oxidation of lipids were followed by faster normalization of bioelectric activity and hemodynamics of the brain and earlier clinical recovery. Microcirculation parameters recorded during biomicroscopy of vessels of the bulbar conjunctiva can be used for evaluating cerebral circulation because vessel responses of the eyeball and the brain are similar. PMID- 1755181 TI - ["Closed" curative surgery and laser therapy in the early postoperative period in patients with chronic suppurative epimesotympanitis]. AB - Taking into account the severity of middle ear pathology and the Eustachian tube function, three methods of "closed" surgery were applied to 132 patients with chronic purulent-caries epimesotympanitis. On post-operation days 2-15, 85 patients were exposed to internal or external laser therapy. As a result, the post-operation therapy period was 5-6 days shorter and the healing quality of the treated ear a year after was better than in the absence of laser therapy. It is concluded that the method of "closed" surgery should be chosen on an individual basis and that its combination with early post-operation laser therapy yields good results. PMID- 1755182 TI - [Amplitude and time characteristics of latent auditory evoked potentials in occupational hearing disorders with and without the recruitment phenomenon]. AB - Cortical evoked potentials (CEP) of workers exposed to industrial noise were recorded by an Amplaid MK-6 unit (Italy). They suffered from neurosensory hypoacusis with or without the recruitment phenomenon. The results were compared with those derived from patients with neurosensory hypoacusis of vascular origin, aggravated by the recruitment phenomenon, and in the cortical structures of the hearing organ in the case of neurosensory hypoacusis of both vascular and noise origin. Increase of the N2 with observations made on normal controls who were not exposed to industrial noise. CEP were found to give reliable information about changes peak latency may be used for differential diagnosis of neurosensory hypoacusis of vascular or noise origin. Decrease of the P2--N2 amplitude in response to 1 kHz stimulation may also help discriminate neurosensory hypoacusis of vascular or noise origin. PMID- 1755183 TI - [Problems of diagnosis and treatment of otogenic abscesses of the brain in children]. AB - In 1947-89, 49 children with otogenic abscesses of the brain and cerebellum were treated in the ENT department of the Kuban Medical Institute. During the first two decades the number of these patients was 34 and during the second two decades it was 15, i.e., the number decreased two-fold. In 25 cases, abscesses were located in the temporal lobe, in 14 cases--in the cerebellum, and in 10 cases, multiple abscesses of different localization were diagnosed. For diagnostic purposes electroencephalography, echoencephalography, angiography, pneumography and ventriculography were used although they were sometimes inefficient, especially in the cases of multiple abscesses. Computer tomography made it possible to determine not only the number but also specific localization of abscesses. The method was applied in 8 cases. After proper examination and treatment all the patients recovered. Out of 49 patients 28 recovered and 21 died. Out of 34 patients treated during 1947-67, 17 recovered and 17 died while out of 15 patients treated during 1968-1989, 11 recovered and 4 died. It can be concluded that a significant reduction of the number of cases with brain abscesses and a substantial increase of the success rate can be attributerd to the advanced methods of their detection (echoencephalography and computer tomography) and more efficient methods of therapy of middle ear suppuration. PMID- 1755184 TI - [Surgical correction of external nose deformities]. AB - During surgical elimination of external nose deformation biologically inert prostheses were used. In the post-operative period low-intensity laser therapy was applied. No adverse effects of corundum ceramics were noted. The procedure of posterior tamponade was modified to ensure complete isolation of the nasopharynx during surgical manipulations on the external nose skeleton. PMID- 1755185 TI - [Rational selection of vasoactive drugs for the treatment of patients with vestibular dysfunction]. PMID- 1755186 TI - [Indicators of general and local immunity in chronic and neoplastic processes in the head and neck areas]. AB - Total and secretory immunity was investigated in healthy people, patients with chronic ENT pathologies, and patients with tumors of the oral cavity, larynx and laryngopharynx. It was found that chronic inflammation was followed by a decline of topical defence and a decrease of total immunity. In cancer patients these changes were aggravated. Topical immunity disorders included mainly secretory immunoglobulin A and were most pronounced in patients with tumors localized in the oral cavity. PMID- 1755187 TI - [Histomorphology and histochemistry of acquired scars of the laryngo-tracheal regions in children]. AB - Acquired scars of the tracheolaryngeal compartment dissected during surgery of 28 children (35 samples) were taken under histological and histochemical examination. In most cases, scar tissues-showed signs of chronic inflammatory infiltration, pronounced changes of the microcirculatory bed, dystrophic and destructive processes, continuous formation of granulation foci and subsequent fibrosis, fibrotic changes in muscles and noticeable dystrophic and metaplastic changes of the epithelium. This points to changes in the relationship between inflammation and regeneration and persistence of inflammatory, sclerotic and dysplastic processes which may cause recurrent development of stenotic scars after their removal. PMID- 1755188 TI - [Measurement of local blood flow in the nasal mucosa by the method of hydrogen clearance]. AB - The hydrogen clearance method was used to measure local blood flow in the inferior concha nasalis of 22 patients, aged 18 to 48 years. According to the method, the nasal mucosa was saturated with hydrogen and the rate of hydrogen washout was recorded in the form of hydrogen clearance curves. The response was tested by applying 0.1% epinephrine solution and the volume blood flow velocity was calculated. In response to epinephrine, blood flow velocity in the nasal mucosa diminished significantly. The hydrogen clearance method allowed an accurate quantitative evaluation of the volume blood flow velocity in a limited area of concha nasalis. The epinephrine test demonstrated a high sensitivity of the method that gave an adequate idea of mucosal microcirculation. This method, together with other procedures, can be used to examine the nasal mucosa. PMID- 1755189 TI - [Surgical correction of unilateral congenital choanal atresia]. PMID- 1755190 TI - [Characteristics of the clinical course and treatment of epitympanitis with cholesteatoma in children]. AB - A specific form of chronic epitympanitis has been identified in children. This pathology includes tympanic membrane perforation above he lateral process of the malleus and is termed cholesteatomic epitympanitis . This is because it is accompanied by epidermis growth across the perforation into Prussak's space. This form of epitympanitis occurred in 40 (75%) children out of 53 cases operated during 10 years. It is underlined that this pathology can hardly be diagnosed since it often develops together with sclerosis of mastoid cells. These children had frequent recurrent otitis media. An immediate cause was Eustachian tube closure, often with adenoid vegetations. Adenotomy was performed in 17 (42.5%) children. All patients underwent radical surgery; 16 showed large cholesteatoma, 5 developed intracranial complications, 2 of whom had sinus thrombosis and sepsis. One of operative findings was delineation of the attic from the mesotympanum and the tympanic ostium of the Eustachian tube. PMID- 1755191 TI - [A case of vestibular neuronitis after acute respiratory infection]. PMID- 1755192 TI - [Status of the cochleo-vestibular analyzer in a patient with chronic otitis media and renal tuberculosis]. PMID- 1755193 TI - [Pyocele of the frontal sinuses and ethmoid labyrinth complicated by osteomyelitis of the frontal bone and extradural abscess]. PMID- 1755194 TI - [Multiple abscesses of the cerebellar hemisphere in a child with otogenic meningoencephalitis and thrombosis of the sigmoid sinus]. PMID- 1755195 TI - [Orthopantomography in the roentgenological diagnosis of ORL diseases]. PMID- 1755196 TI - [Safe conchotomy]. PMID- 1755197 TI - [A polyvinyl mask for external nose fixation]. PMID- 1755198 TI - [A spatula for drug pulverization]. PMID- 1755199 TI - [Teaching otorhinolaryngology at the pediatric departments of medical schools]. PMID- 1755200 TI - [Therapeutic tactics in isolated and combined exudative ethmoid sinusitis in children]. AB - This paper presents the results of treatment of 81 children, aged 5 to 14 years, suffering from exudation ethmoid sinusitis; isolated ethmoid sinusitis was diagnosed in 17.8% and ethmoid sinusitis combined with maxillary sinusitis was detected in 61.7% cases. Most sinusitis cases (82.7%) were diagnosed in 5 to 10 year-old children. The ethmoidal labyrinth and maxillary sinus were treated by the puncture method, infection of other paranasal sinuses being excluded by the application of antibacterial, enzymic, corticosteroid drugs, immune agents, and adenotomy. Antibiotic therapy of 2 weeks in duration applied to the ethmoid labyrinth and maxillary sinus was more efficient when compared to the sinus treatment alone. The stable clinical effect was seen in 86.4% cases. This therapeutic approach can find application in practical otolaryngology. PMID- 1755201 TI - [Isosorbide dinitrate tolerance in the treatment of patients with angina pectoris and the effect of addition of captopril on therapeutic results]. AB - The authors investigated in patients with stable angina the influence of a single dose and of long-term administration of isosorbide dinitrate alone and combined with captopril. Administration of 40 mg Iso-Mack ret. every 8 hours for four weeks did not lead to the development of tolerance. However, captopril added to isosorbide dinitrate tends to improve the investigated indicators after a single dose as well as after long-term treatment. It is probable that concurrent administration of the two drugs causes addition of their vasodilatating action and thus the vascular resistance declines, as well as the cardiac pre-load and after-load and the oxygen consumption of the heart muscle. The authors discuss possible mechanisms of the increased vasodilatation after addition of captopril. PMID- 1755202 TI - [Focal segmental glomerulosclerosis]. AB - Focal and segmental glomerulosclerosis accounted for 4.1% of all primary glomerulopathies. Typical signs of focal and segmental glomerulosclerosis were striking arteriolosclerosis on histological examination, the urinary syndrome of high proteinuria with mild haematuria and frequent nephrotic syndrome. The ten year cumulative percentage of remissions was 30%. Patients with remission had at the time of biopsy a normal serum creatinine level and no or minimal regressive tubulointerstitial changes. The ten-year cumulative percentage of renal failure was 40%. Presence of nephrotic syndrome, extracapillary proliferation and advanced tubulointerstitial changes, tended to shorten a kidney survival. In one third of the patients the serum creatinine level rose by more than 50 mol/1/year. PMID- 1755203 TI - [Changes in hemostasis in ischemic heart disease in advanced age]. AB - In a group of 178 patients with different forms of ischaemic heart disease and in a group of 40 healthy controls the authors made complete examinations of haemostasis to provide laboratory evidence of a state of hypercoagulation. They assessed the relationship of different coagulation factors between patient groups and healthy controls formed by a group of blood donors. They draw attention to the significant age dependence of the majority of coagulation factors. As apparent from the results, the highest incidence of hypercoagulation was recorded in patients with myocardial infarction. PMID- 1755204 TI - [Use of hemoperfusion and cholinesterase in acute poisoning with organophosphate cholinesterase inhibitors--clinical analysis of 50 patients]. AB - The authors present a retrospective analysis of 50 patients with acute intoxication with various organophosphate cholinesterase inhibitors who were treated in the course of 8 years by comprehensive conservative and extracorporeal elimination treatment. The mean age of the patients was 38 years. During therapy conservative treatment was used (gastric lavage, repeated lavage of the large intestine, forced diuresis, TMB-4 fusion through activated carbon, amberlite XAD 2 and XAD-4, haemodialysis). A total of 63 haemoperfusions and 15 simultaneous haemoperfusions with haemodialysis were performed. Treatment was successful in 92%. The results of treatment depended on early attendance of the patient in the dialyzation centre, on the onset of intense comprehensive treatment and the concurrent presence of other diseases. PMID- 1755205 TI - [Evaluation of heart disease in rheumatoid arthritis using echocardiography]. AB - The authors examined, using one- and two-dimensional echocardiography, 95 patients with rheumatoid arthritis and 11 patients with lupus erythematodes generalisatus. They revealed acute and chronic changes on the pericardium, impaired left ventricular function and valvular changes in percentages which are not negligible. Although the problem of the aetiopathogenesis of these pathological changes is frequently speculative, their detection is of considerable importance for further treatment and the life-style of these patients. Echocardiography is a suitable method for the comprehensive examination of patients with rheumatoid arthritis, in particular when the course is severe or when patients of advanced age groups are involved. PMID- 1755206 TI - [The nephrotic syndrome in renal biopsies]. AB - Among 1,499 representative renal biopsies in 278 cases nephrotic syndrome was diagnosed. In the latter only in 201 glomerulonephritis was confirmed by biopsy and in 77 (more than one quarter) the bioptic finding was different. The authors attempt to analyze the essential feature of nephrotic syndrome focused on the glomerular basal membrane and surrounding structures. PMID- 1755207 TI - [Comparison of the diagnostic contribution of rheography and ultrasound in diabetic macroangiopathy of the lower extremities]. AB - In a group of 140 patients with diabetes mellitus ultrasonographic Doppler examination revealed a 30% incidence, rheographic examination a 34% incidence (p greater than 0.05) of macroangiopathies of the lower extremities. The asset of rheography was the ability to differentiate between pathological functional (21% incidence) and organic changes (13% incidence). The contribution of sonographic examination was the localization of the portion most severely affected by the macroangiopathy. The most frequent variant was general affection of the distal portion of extremities, followed by predominating affection of the posterior tibial artery and affection of the entire circulation of the lower extremity. In the authors' practice rheography is the basic examination. In the event of revealed pathological changes it is supplemented by sonographic Doppler examination. PMID- 1755208 TI - [Arteriosclerosis risk factors in the offspring and siblings of type 2 diabetics]. AB - Risk factors of atherosclerosis were examined in 63 offspring and 30 siblings of type 2 diabetics and in 22 controls. Clinical complications of atherosclerosis were not found very frequently in direct relatives of diabetic patients. Diabetes was detected in 17% siblings, an impaired glucose tolerance in 11% of the offspring and in 33% siblings. The offspring of diabetics had higher blood sugar values and serum insulin levels on fasting and after stimulation, as compared with controls; as to other metabolic parameters lipids and apolipoproteins, body mass indexes, uricaemia, glycated proteins, C-peptide), the two groups did not differ significantly. In middle age, i.e. in siblings of diabetic patients, the incidence of obesity rose significantly as well as hyperlipoproteinaemia type IV and hypertension, while smoking was less common than in offspring. The glucose tolerance deteriorated further, although the insulin levels did not increase substantially. The mentioned findings indicate the orientation for preventive provisions in families of type 2 diabetics. PMID- 1755209 TI - [The effect of age and educational level on the risk profile of men and women in industrial occupations]. AB - The authors investigated a population group of 660 men and 440 women aged 35-60 years selected in the Skoda works and examined as part of the integrated programme of prevention of chronic non-infectious diseases. The risk profile of subjects associated with the life-style of the population was evaluated with regard to sex, age and education. It was revealed that the blood pressure rises with age and body weight in men and women. With rising body weight rises also the triglyceride and uric acid level and in women also the total cholesterol level. The authors confirmed the relationship between smoking and the thiocyanate blood level. The magnesium level declines with age in both sexes and correlates with the reported alcohol intake. Men and women with higher education smoke less, have a lower body weight and lower triglyceride blood levels. Women have also a lower total cholesterol level. University educated men consume less alcohol, while the reverse is true in university educated women. PMID- 1755210 TI - [Echocardiographic detection of wedged emboli in the right heart in patients with pulmonary embolisms]. AB - The authors describe two case-histories of patients with the clinical picture of pulmonary embolism where on echocardiography a mobile formation in the right atrium was detected. In both patients the embolus of peripheral origin wedged in the right atrium was removed by surgery. PMID- 1755211 TI - [Sudden death in rheumatoid arthritis with cervical myelopathy]. AB - The authors describe an uncommon case of sudden death in a 53-year-old female patient with cervical myelopathy associated with rheumatoid arthritis stage IV/C. The patient died six hours after a drop of the blood pressure to undetectable values was found. Malignant hypotension of central origin which could not be influenced by pharmacological treatment was involved. It was due to compression of the upper cervical spine by a partly dislocated dens of the epistropheus and subsequent afferent spinal oedema which affected the vasomotor centre in the brain stem. The clinically suspect cause of death was confirmed by autopsy: Myelogenic shock. PMID- 1755212 TI - [Antibiotics and antimycotics in oncology]. AB - The submitted review gives an account of therapeutic and prophylactic indications in oncology, in aimed, not aimed (empirical) treatment of febrile neutropenic patients, prophylaxis of infection during neutropenic episodes and selective decontamination before and during transplantation of bone marrow, focused on new antimicrobial and antimycotic agents. PMID- 1755213 TI - [Echocardiographic findings in cerebrovascular accidents]. AB - The authors present a review on the frequency and causes of cardiogenic systemic embolism and on the influence of damage of the central nervous system on the heart muscle. 10-20% of ischaemic cerebrovascular attacks are of cardioembolic origin. In patients with chronic atrial fibrillation the risk of a cerebrovascular attack is six times higher than in the corresponding population with a sinus rhythm. Views on the preventive administration of anticoagulants differ so far. In extensive myocardial infarctions of the anterior wall thrombi in the left ventricle are present in 30-40%. Thrombolytic treatment affects their formation; so far it is not clear whether it reduces the risk of embolization. With technical advances in echocardiography, and in particular transoesophageal echocardiography, attention is focused on abnormal findings in patients with cerebrovascular attacks without manifest heart disease. Most frequently in these patients a prolapse of the mitral valve is found, a foramen ovale patents, an aneurysm of the atrial septum, sometimes thrombi in the left auricula atrialis of an otherwise quite normal heart. A rare finding are cardiac tumours, systemic embolism being frequently their first clinical manifestation. An indicator of high risk of thromboembolism is probably a spontaneous echo contrast in the left atrium, detected reliably only from an oesophageal approach. In the second part the authors summarize contemporary knowledge on the effect of damage of the central nervous system on cardiac action. Cerebral injury or haemorrhage accompany kinetic disorders of the left ventricle of varying impact. Myocardial damage is caused by a high catecholamine level and can be prevented by administration of beta blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755214 TI - [Preoperative examination and preparation of patients with ischemic heart disease from the viewpoint of the internist]. AB - In the presented review the authors discuss briefly the effect of anaesthetizing substances on the heart muscle. Examinations to which the patient with IHD should be subjected before a cardiac operation and the surgical risk are discussed in the part on preoperative examination of the patient with IHD. The paper deals in detail with the preoperative preparation and contemporary views on the subject with specific views on different drugs. In the conclusion the authors present the results of the work of the consultant out-patients department of the First Medical Clinic of the Faculty Hospital and policlinic in Kosice which are a practical evaluation made by the specialist in internal medicine of the theoretically elaborated preoperative preparation of patients with IHD. PMID- 1755216 TI - [Blast injuries (a review of the literature)]. PMID- 1755215 TI - [How to avoid failure and complications in guided punctures]. AB - The author discusses some actual procedures associated with diagnostic and therapeutic interventions using ultrasonography. Based on his own experience from practice, documented in tables with brief comments (attached to the paper) and with regard to data in the literature, he draws attention to some facts (technique of puncture, selection of instruments, local anaesthesia, method of drainage) which may to a varying extent influence the results of aimed puncture or cause possible complications. PMID- 1755217 TI - [The organization of the delivery of specialized vascular trauma care for victims (1)]. PMID- 1755218 TI - [The diagnostic and treatment characteristics of modern combat trauma to the blood vessels]. PMID- 1755219 TI - [The diagnosis and treatment of lung contusions of gunshot origin]. AB - The analysis of penetration wounds accompanied by lung hurts has shown that the contusion of lung parenchyma had a quite definite clinic characteristic. The gravity of breathing disorders always depends on the volume of lung affection and blood losses. A successful treatment of lung contusions depends upon an early application of adequate measures, in which artificial lung ventilation performs a leading role. PMID- 1755220 TI - [Experience in the diagnosis and treatment of heart wounds]. PMID- 1755221 TI - [Transosseous osteosynthesis in the system for treating victims with penetrating gunshot wounds of the large joints of the upper extremity]. PMID- 1755222 TI - [The use of electromyostimulation for preventing and treating hypodynamic disorders in gunshot injuries to the extremities]. AB - It was found out during the study of multichannel electromyostimulation (EMS) influence upon human organism and the adequacy of its physical load to adoptive and compensative possibilities of cardiovascular system that that method was effective for prophylaxis of disorders and rehabilitation of nervous and muscular system, and locomotor apparatus after a short period of hypodynamia. The EMS increases the working capacity of nervous and muscular apparatus, mass of muscles and their contraction strength due to improvement of nervous and muscular conductivity and blood supply of the extremity. The efficiency of EMS decreases considerably when degenerative changes are taking place. PMID- 1755223 TI - [The rehabilitation of those with hand injuries]. PMID- 1755224 TI - [The neurological manifestations of blast trauma to the brain]. AB - The article describes mechanisms of cerebral injuries and clinical symptomatology of light and medium trauma. It is stressed that a certain succession in medical and diagnostical measures must be observed, as well as physicians of several medical specialties must participate in the treatment of such cases. There is a description of morphological picture of cerebrum in this type of trauma. The article also shows pathogenetical and clinical differences between burst and mechanical brain injuries. PMID- 1755225 TI - [Experience in rendering anesthesiological care to the wounded in Afghanistan]. PMID- 1755226 TI - [The experience of Soviet military medicine in Afganistan: 1979-1989]. PMID- 1755227 TI - [Medical support for the 40th Army (facts and figures)]. AB - The article summarizes the activities of the 40-th Army medical service during the war in Afghanistan (1979-1989). The structure of injuries was examined depending on the type of a wounding missile and localization of wound. The scheme of air evacuation of sick and wounded is enclosed. There is dynamics of statistic indexes which characterize the number of rejoined servicemen, medical aid rendered to civil population, etc. PMID- 1755228 TI - [Infusion-transfusion therapy in chest wounds at medical evacuation stages]. AB - On the basis of the analysis of medical publications and practical experience in surgical care to the wounded the article discusses the tactics of infusion and transfusion therapy that should be used at the stages of medical evacuation. The authors emphasize the importance of the infusion therapy nearness to the place of accident, the necessity to provide medical personnel with adequate facilities for this task, careful attitude for autologous blood of wounded, blood reinfusion during pleural puncture or thoracotomy [correction of teracotomia]. The schemes of infusion and transfusion therapy for each stage of medical evacuation are enclosed. PMID- 1755229 TI - [The clinico-laboratory characteristics and treatment of typhoid fever combined with tertian malaria]. PMID- 1755230 TI - [The work quality indices of specialists in preventive medicine]. PMID- 1755231 TI - [Trends in the improvement of medical prophylaxis]. PMID- 1755232 TI - [The status of and ways for further improvement in the medical support of Air Force personnel]. PMID- 1755233 TI - [At the Central Military Naval Hospital]. PMID- 1755234 TI - [The surgical aspects of the lessons of the war in Afghanistan]. AB - There were no two identical wars in human history. From the medical point of view, the civil war, which is still going on in Afghanistan, also has its own face. The structure of sanitary losses, the character, gravity, and peculiarities of gunshot pathology give the possibility to call it as a mine war, because of its massive and, above all, effective mine warfare. The war in Afghanistan conclusively proves the predominance of blast injuries over other sanitary losses in the structure of combat surgical pathology, that may be considered as a common feature for the wars of century XX. The mine blast trauma must be regarded as a combat heavy concomitant trauma or gunshot blast polytrauma. This statement is the basic one for the rest of medical lessons gained from the war in Afghanistan. Using the comparative analysis of the different functions of medical service of two armies, the article shows the priority of organizational aspects for care and treatment of the wounded in war. PMID- 1755235 TI - [The posttraumatic stress syndrome in war veterans with a history of combat mental trauma]. PMID- 1755236 TI - [The responsibility of medical workers in cases of their violation of their professional obligations (1)]. PMID- 1755237 TI - Safe use of pesticides. Fourteenth Report of the WHO Expert Committee on Vector Biology and Control. PMID- 1755238 TI - WHO Expert Committee on Biological Standardization. Forty-first Report. PMID- 1755239 TI - [Purpura fulminans--aspects of etiopathogenesis, clinical aspects, diagnosis and therapy]. PMID- 1755240 TI - [Clinical aspects and follow-up of Wegener's granulomatosis]. PMID- 1755241 TI - [Anticytoplasmic antibodies in Wegener's granulomatosis and other kidney diseases]. PMID- 1755242 TI - [Therapeutic aspects of Wegener's granulomatosis]. PMID- 1755243 TI - [Pulmonary parasitoses as differential diagnosis of lung tuberculosis]. PMID- 1755244 TI - [Pleurodesis with electrically activated autologous blood in recurrent pleural effusion--preliminary report]. PMID- 1755245 TI - [International classification of health problems in basic medical care]. PMID- 1755246 TI - [In memory of Arthur Kronfeld]. PMID- 1755247 TI - [Diagnosis and surgical therapy in congenital ectasias of the intra- and extrahepatic bile ducts]. AB - 31 patients with congenital ectasias of extra- and intrahepatic bile ducts have been diagnosed and treated between 1980 and 1991 at the Charite. 7 ectasias belonged to type I, two to type II, three to type III, four to type IV and fifteen to type V of classification by Alonso-Lej/Todani. The age of affection was between 8 and 80 years. Symptoms are not specified and directed to affection of liver or bile ducts. Main symptoms of type I--III were complaints in the upper abdomen and jaundice, of type IV--especially after previous surgery--fever and also jaundice. Complaints in the upper abdomen and fever dominated in type V. The right diagnosis succeeds at 27 out of 31 patients with direct cholangiography. Sonography and computerized tomography were not always in a position to attach the clinical picture to congenital ectasias. In extrahepatic ectasias is the resection of bile duct cysts--carried out in 2/3 of all cases--the therapy of choice. Once was found a carcinoma in a resected bile duct cyst 23 years after a choledochocysto-jejunostomy. By Caroli syndrome the therapy must be fixed individually. 6 patients were supplied operative (liver resection, choledochotomy, papillotomy, extraction of lithiasis). Instrumentally were carried out 9 endoscopic papillotomies with extraction of concrements and 6 lay ins of internal drainage catheters were done. PMID- 1755248 TI - [Intraoperative cholangioscopy]. AB - There are the best diagnostic results by endoscopic examination of the common bile duct. Both rigid and flexible instruments can be used for the examination. The advantages and disadvantages will be discussed. The stump of the cystic dust will be useful to clarify pathological finding by x-ray in the distal bile duct. Usually, however, the instrument is introduced by means of a choledochotomy. In the last 16 years in 1023 cases the bile duct were examined endoscopically, 330 via the cystic duct, 693 via a choledochotomy. Stones were detected in 541 cases (52.9%), in 16 cases (2.9%) a stone was overlooked. Severe complications by operative choledochoscopy were not seen. PMID- 1755249 TI - [Elective cholecystectomy with and without subhepatic drainage. A controlled, prospective study]. AB - Based on the data of 56 patients undergoing elective cholecystectomy the value of subhepatic drainage is evaluated in a randomized controlled clinical trial. The design of the study and the perioperative management of the patients are described in detail and the results analyzed according to clinical course, blood tests and abdominal ultrasound. PMID- 1755250 TI - [Anomaly of the pancreatico-biliary junction and etiology of choledochal cysts]. AB - The etiology of choledochal cysts isn't yet clarified unequivocably. Numerous theories have been worked out. One of them is the 1969 by Babbitt postulated "common-channel"-theory, which is based on an anomaly of the pancreaticobiliary connection. In case of a fusion of ductus choledochus and ductus pancreaticus widely before the papilla of Vater and the formation of a common channel with a minimum length of 15 mm the reflux of pancreatic secretion into the off-leading biliary ducts may occur and choledochal cysts may develop. In order to check up this hypothesis we evaluated retrospectively pictures of a direct cholangiography (ERCP, PTC and/or intraoperative cholangiography) of 26 patients suffering from type I, IV and V ectasias of the biliary ducts according to Todani. We found a common channel with an abnormal length in 8 of 12 patients suffering from extrahepatic ectasias of the biliary duct type I and IV (66%), but we didn't find it in patients with type V intrahepatic ectasias of the biliary duct. This analysis may be recognized as a reference to the truth of the Babbitt-theory. PMID- 1755251 TI - [Obstruction of the small intestine caused by a gallstone 13 years following cholecystectomy]. PMID- 1755252 TI - [Acute gallbladder symptoms caused by torsion of the gallbladder]. PMID- 1755253 TI - [Radiation therapy in breast carcinoma]. AB - Strategies in treating breast cancer have been changed in the last years. In Stage I and early II radical operation techniques have been used not more. Today conservative methods are preferred in combination with axillary lymphonodectomy. This implies necessity of postoperative irradiation. Longterm results are not different between breast preserving methods and radical mastectomy. Cosmetic results can be excellent following high doses of radiation. Side effects are minimal and of non important clinical value. If there is a local recurrence or a second primary tumor, a secondary mastectomy can solve the problem in many cases. PMID- 1755254 TI - [Cytopathology of the breast. 1. Secretion and nipple cytology]. AB - Cytological examinations of breast secretions, nipple smears and breast fine needle aspirates can establish important diagnostic findings provided that technical conditions and methodical advantages and disadvantages are taken into consideration. The first part of the paper is dealing with clinically relevant aspects of secretion and nipple cytology. These simple examinations are applicable by every gynaecologist. The source of cell material is the spontaneous exfoliation, which should be increased in nipple smears by additional procedures. Diagnostic findings of secretion cytology can be obtained in breast cancer, duct papilloma, cystic fibrosis, and inflammatory lesions. The value of secretion cytology for breast cancer detection is limited, because pathological secretion is only induced in a small number of patients. Cytological examinations of nipple lesions are useful especially in the presence of Paget's disease and other tumors of the nipple. Limitations are caused by difficulties in cell sampling. Easy practicability and little alteration of the patient are the major advantages of the secretion and nipple cytology, which stands opposite a limited sensitivity as disadvantage. PMID- 1755255 TI - [Results of a psycho-oncological project at the University Women's Hospital Leipzig]. AB - This paper deals with a synoptic description of experiences of an inter disciplinary oncologic project by means of its three main components--theoretical research, further education and qualification as well as psychological intervention program. It was shown that team work between physicians, nurses and psychologists led to an new insight and higher working effectivity with minimal subjective stress. This team work led also to the creation of favourable conditions for an appropriate management of diseases through an intensive and integrated patient care. The application of this model project in the routine oncological follow-up would be recommended. PMID- 1755256 TI - The intracellular enzymatic response of neutrophils and lymphocytes in patients with precancerous states and cancer of the uterine cervix. AB - In patients with precancerous states and cancer of the uterine cervix prior to and after radiotherapy exhibit the decreased activity of neutrophil beta glucuronidase. Moreover, patients treated by radiotherapy before the age 6 to 9 years demonstrate deficiency of N-acetyl-beta-glucuronidase in the above cells. The main finding in lymphocytes of the patients studied was in the appearance by diffusion of the above enzymes and of acid phosphatase in the cytoplasm, reflecting their release from lysosomes and immunological mobilization of these cells. The authors discuss the possible role of neutrophil enzymatic deficiency in lowering the antitumor cytotoxic effect of these cells. PMID- 1755257 TI - [3-dimensional ultrasonic mammography. Tissue differentiation and tissue-specific breast imaging]. AB - This paper presents first results concerning the three-dimensional ultrasonic data acquisition, the textural analysis of different classes of tissues and the tissue-specific display of mastopathic regions within the female breast, revealing its benefit for diagnosis. PMID- 1755258 TI - [Fetal echocardiography. II. Normal and pathological anatomy in real-time ultrasonography]. AB - The paper is a practical approach to fetal echocardiography using real-time ultrasound. The normal sonoanatomy of the fetal heart is presented for the non cardiologist. The basic cross-sectional views are explained as well as the systematic analysis of the different fetal heart structures. The main heart malformations are reviewed with a description of their appearance in prenatal real-time-ultrasound illustrated by some figures. The examination of the fetal heart could be easy learned, but the assessment and the differentiation of congenital heart defects are only possible by a systematic approach, experience and patience. The examination of the fetal heart should be therefore involved in the screening-ultrasound performed by the prenatal sonographer and suspicious findings has to be referred to a perinatal center. PMID- 1755259 TI - [Microsurgical sterility operations in female patients with deficient contralateral tube--pros and cons]. AB - Microsurgical operations of sterility on 39 women with only one remaining tube have been analysed in order to examine the justification of primary operations of sterility on these patients. 13 out of 26 women (50%), who had been followed up for at least 9 months after the operation, have become pregnant. Live birth rate was 30.8% abortion rate 7.7% and the rate of ectopic pregnancies 11.5%. The results correspond to these obtained from women bilaterally operated on, so that microsurgical operations are justified in sterile women with a lacking opposite tube, too. The removal of the opposite tube during the actual operation of sterility is prognostically more advantageous than the exstirpation before it. Salpingectomy has better results than salpingo-oophorectomy. PMID- 1755260 TI - [The effect of physical training on the pharmacokinetics of steroidal contraceptives]. AB - In 8 female sports students (runners) aged 20 and 21 years and 10 women between 20 and 40 years of age, who regularly underwent body building training, serum levels of ethinylestradiol (EE2) and levonorgestrel (LNG) have been determined under conditions of exercise as well as in rest, prior to and following the intake of 1 tablet of Gravistat (0.05 mg EE2, 0.125 mg LNG). Blood samples were obtained at points 0, 2, 6 and 24 hours. Exercise (5000 meter running and intensive body building training of one hour duration, respectively) was started immediately after intake of the steroid combination. There were no significant differences in the serum concentration levels obtained during exercise and rest. But exercise consistently resulted in a slight decrease of EE2 and LNG serum concentrations and the area under curve values. PMID- 1755261 TI - [Tumor recurrence following negative second-look laparotomy in ovarian carcinoma]. AB - Between January 1980 and December 1990, 107 ovarian carcinoma patients in clinical complete remission were submitted to a second-look laparotomy at our department. Borderline carcinomas were excluded from the study. Second-look laparotomy was negative in 78.5% of the cases (84 patients). During the follow-up period after the second-look-laparotomy (mean 59 months, range 6 to 120), a recurrence of the tumour was diagnosed in 7 patients (8.4% false-negative rate). This took place after a mean time of 39 months following the previous negative second-look (range 8 to 108). Three of the recurrences were localized in the pelvis, two in the upper abdomen and two in the paraaortic and supraclavicular lymph nodes, respectively. All patients with a recurrence belonged to the group having received adjuvant chemotherapy for one year after initial surgery. At the present time we lack any means to anticipate which patients with a negative second-look will eventually show a recurrence of their tumour. PMID- 1755262 TI - [15 years Perinatal Center of the Leipzig University]. AB - Report about experiences with developing a perinatal center step by step an the University of Leipzig, primarily directed to improve the results of premature labour, then expanded by intensive diagnostics and treatment and uniform documentation of all risk pregnancies. Perinatal and neonatal mortality decreases following this management. PMID- 1755263 TI - [Surgical therapy and prognosis of vulvar carcinoma]. AB - From 1954 to 1985 211 woman with carcinoma of the vulva were treated at the medical college Dresden. 66 patients were found at the FIGO stage I, 69 at stage II, 50 at stage III, 18 at stage IV; 8 could not be classified. In the total group of woman the cumulative survival rate due to the different stages were: 72% at stage I, 56% at stage II, 28% at stage III and 13% at stage IV. The 5-year survival rates were different in women undergoing a total vulva operation (76%) from vulvectomized women (60%) and partial vulvectomized woman (48%). So the total vulva operation had a great effect on outcome. In female patients which underwent palliative surgical treatment the survival rate could be increased by means of the postoperative radiation therapy. It is a matter of outstanding importance to the vulva carcinoma prognosis to operate radically and as soon as possible. PMID- 1755264 TI - [Purification and survival of retinal ganglion cell]. AB - We had used a specific anti-Thy 1.1 antibody binding method and a nylonmembrane sieve method to isolate and purify retinal ganglion cells from neonatal rats in order to compare the effect of tectal extract on these purified cells retinal ganglion cells. Isolated retinal cell suspension with retinal ganglion cells retrograde-prelabelled with Fast Blue were seeded on culture dishes coated with the specific anti-Thy 1.1 antibody for 30 minutes before nonadherent cells were removed. The percentage purity of the adherent retinal ganglion cells determined microscopically to be 95%. However, the percentage purity of the Fast Blue labelled retinal ganglion cells recovered using the nylon membrane of pore size 15 microns was only 60 +/- 5%. Retinal ganglion cells purified by both methods could survive and grow into large, active neurons with neurite outgrowths in the presence of tectal extract. A MTT colorimetric microassay was used to quantify the survival growth activity of these purified retinal ganglion cells after culture for 24 hours. The result showed that the optical density ratio (+Te/-Te) of the retinal ganglion cells purified by anti-Thy 1.1 antibody binding method was 12.3 (0.111/0.009) and by the nylon membrane method was 6.4 (0.102/0.016), and the optical density ratio of the non-purified retinal cells was 3.8 (0.095/0.025), p less than 0.01 for all 3 sets of results. It was concluded that in the absence of other cells, the purified retinal ganglion cells responded specifically to the trophic activity in tectal extract, the purer the retinal ganglion cells and the clearer the effect. PMID- 1755265 TI - [Lysosomes in the regulation of hormone secretion in endocrine cells]. AB - Enzyme cytochemistry and immunocytochemistry were utilized to study the morphological alterations of the lysosomes and associated crinophagic and autophagic structures in the hypo-secreting pituitary gonadotrophin and Leydig cells induced by exogenous androgen. The lysosomes and autophagic vacuoles in the electron micrographs were quantitatively analysed. The morphological and quantitative data led to the following conclusions: 1) The hypo-secreting gonadotrophin showed an increase in the number of lysosomes and an enhancement of crinophagy. It demonstrated once again that the lysosomes in the protein and polypeptide hormone secreting cells play a role in the regulation of secretion process by means of the crinophagy. 2) The hypo-secreting Leydig cells showed an increase in the number of lysosomes and an enhancement of autophagic activity. This indicated that the lysosomes in the steroid hormone secreting cells also function in the regulation of hormone secretion but by means of autophagy which scavenge a part of steroid-producing apparatus and hormone. The autophagy might have similar effect in regulation of steroid secretion to the crinophagy in regulation of protein secretion. PMID- 1755266 TI - [Characteristics and inhibitory action of monoclonal and polyclonal antibodies against the retinal ganglion neuronotrophic factor (RGNTF)]. AB - We have immunized Balb/c mice and rabbits with a minute quantity of a 30 kD neuronotrophic factor which was isolated from the extract of newborn rat tectum (Te) by Phast System gel electrophoresis. Splenic cells from the immunized mice were hybridized with NS-1 mouse myeloma cells. Three clones were selected from 576 wells of hybridomas and were capable of secreting monoclonal antibodies specific to the retinal ganglion neuronotrophic factor (RGNTF-MAbs), namely A1, D3 and E8. Subtyping of the three monoclonal antibodies revealed that A1 and D3 are IgG3 and E8 is IgM. They maintained secreting antibodies even after six months of culturing in vitro. In order to determine the specificities of these antibodies, we have used their ascites fluids containing antibodies at a different dilutions to study their effects on the survival of retinal ganglion cells in vitro. The results indicated that at the dilution ranges of 1:250 to 2000, all three monoclonal antibodies exhibited inhibition on the survival of retinal ganglion cells and the inhibition increased with increases in antibody concentrations; especially at a dilution of 1:250, the E8 monoclonal antibody reaching 70% inhibition and A1 and D3 reaching 66% and 62% inhibition, respectively. Polyclonal antibodies from rabbits exhibited similar but weaker results of inhibition. We can conclude that the monoclonal and polyclonal antibodies can specifically inhibit the activity of the 30 kD retinal ganglion neuronotrophic factor. PMID- 1755267 TI - [Psychosomatic approach in digestive pathology. Diagnostic and therapeutic value]. PMID- 1755268 TI - Serum pancreatic isoamylase activity in pancreatic disease. AB - The diagnostic value of serum amylase determination for pancreatic disease has been questioned due to its lack of specificity. Several methods have been developed to separate the tissue-unspecific salivary fractions from the tissue specific pancreatic fractions. Agarose or cellulose acetate gel electrophoresis are most suitable for clinical practice. The isoamylase patterns were studied by agarose electrophoresis in 55 patients with known pancreatic diseases (acute pancreatitis, pancreatic pseudocysts, exocrine pancreatic insufficiency and pancreatic carcinoma). Increased P-type isoamylase seems to be more sensitive than total amylase in diagnosing acute pancreatitis, while identification of the minor isoamylase P3 is more specific and could have a prognostic value. Detection of low P-type isoamylase levels is an easy method to diagnose exocrine pancreatic insufficiency. Furthermore, a group of patients with pancreatic disease (Pa), was compared with a group of patients with biliary disease without clinical evidence of pancreatic involvement (Bi), and patients with abdominal pain, without evidence of biliary or pancreatic disease (Ab). More than half of the Bi patients presented with abnormal P isoenzyme patterns, whereas 72% of the Ab patients had a normal pattern. Only P3 could distinguish between the Bi and Ab group. This might point to pancreatic involvement in patients presenting with biliary disease, only detected by isoamylase analysis. PMID- 1755269 TI - [Pharyngo-laryngeal consequences of gastroesophageal reflux. Value of esophageal pH measurements in 74 patients]. AB - Ambulatory 24 hour oesophageal pH monitoring was performed in order to detect gastro-oesophageal reflux disease (GERD) in 74 patients presenting with poorly explained ear-nose-throat complaints. A significant number of these patients also benefited from other currently used methods for diagnosing GERD. Oesophageal pH monitoring demonstrated GERD in half of the patients. For atypical GERD, 24 hour oesophageal pH-monitoring seems to be the most sensitive procedure. PMID- 1755270 TI - Scintigraphy with Indium-labelled leukocytes in acute pancreatitis. AB - The authors assessed the clinical and prognostic value of abdominal (ASCI) and pulmonary (PSCI) scintiscans with 111Indium-labelled leukocytes in the early phase of acute pancreatitis. A grading scale was constructed for both ASCI (scored 0 to 3) and PSCI (scored 0 to 2) according to the intensity of isotope fixation versus adjacent structures. Results were compared in accordance to the presence or absence of a Ranson's score greater than or equal to 3, the presence or absence of respiratory failure and of late pancreatic complications. ASCI showed an important lack of specificity making its use uninteresting. PSCI revealed a very significant correlation with evaluation by Ranson's score and appears to have a high sensitivity and specificity to evaluate the patients who will develop ARDS or risk of ARDS. This demonstrates the pathophysiological role of leukocytes in the early phase of severe acute pancreatitis. The test might also be a reliable test for the assessment of therapeutic efficiency in acute pancreatitis. PMID- 1755271 TI - Direct and indirect evidence for the involvement of prostaglandins in the secretagogue action of rhein anthrone in the small intestine. AB - The present study was undertaken to investigate the involvement of prostaglandins in the secretagogue action, observed after intraduodenal administration of rhein anthrone and rhein in rats. After intraduodenal administration of rhein anthrone (50 mg/kg), the active metabolite of sennosides, a very marked increase of secretion was observed compared to control. The amount of secretion was calculated by dividing the total weight of the small intestine, obtained 30 minutes after administration of the drug, by the total length. The effect seen with rhein (50 mg/kg) is far less pronounced than that with rhein anthrone and is not significant when compared with control. Pretreating the animals with indomethacin (15 mg/kg, p.o., 1 hour in advance) or with ibuprofen (15 mg/kg, p.o., 1 hour in advance) largely prevents the secretagogue effect of rhein anthrone, suggesting that prostaglandins play an important role in the observed pharmacological action. This idea is reinforced by the observation that pretreatment with hydrocortisone (50 mg/kg, p.o., 6 hours in advance) is also able to counteract the effect of rhein anthrone. After administration of rhein anthrone, an almost tenfold increase of the tissue content of prostaglandin E2 was observed. Here again, the results with rhein were far less pronounced. It is concluded that prostaglandins play an important role in the secretagogue action of rhein anthrone. PMID- 1755272 TI - Juxtapapillary duodenal diverticula and diverticula of the colon: is there a general "gastrointestinal diverticular disease"? AB - Both juxtapapillary duodenal diverticula and colon diverticula are acquired lesions, the pathogenesis of which is believed to involve the influence of high intraluminal pressure on loci minoris resistentiae in the gastrointestinal wall. We wanted to investigate whether juxtapapillary duodenal diverticula and colon diverticula occur independently, or whether they are part of a hypothetical general "gastrointestinal diverticular disease". 239 patients with juxtapapillary duodenal diverticula were identified in 2231 patients undergoing ERCP. Complete radiology data were available in 119/239 patients. Double contrast barium enema had been performed in 28/119 patients. In these patients, colon diverticula were present in 9/20 women and 1/8 men. The frequency of colon diverticula in these patients was compared with randomly chosen age- and sex-matched controls, for whom barium enema results were available. In these controls, 9/20 women and 1/8 men also had colon diverticula (n.s.). We conclude that after stratification for age and sex, the occurrence of colon diverticula is not higher in patients with juxtapapillary duodenal diverticula than in the general population. Juxtapapillary duodenal diverticula and colon diverticula thus occur independently. These data are not in favor of the existence of a general gastrointestinal diverticular disease. PMID- 1755273 TI - Draft protocol for oesophageal pH monitoring. pH Monitoring Working-group of the Belgian Group of Paediatric Gastroenterology and Nutrition. PMID- 1755274 TI - [Cystoid pneumatosis of the intestine. Apropos of 2 case reports]. AB - The authors report two cases of pneumatosis cystoides intestinalis involving the small intestine. The first patient, a 35-year-old man treated for duodenal ulcer since 1976, presented with digestive haemorrhage in 1981 for which a vagotomy and a gastroduodenoanastomosis were performed. He was seen in 1986 for a post-bulbar stenosis. On the plain abdomen radiography there were gaseous formations in the sub-phrenic region. At operation the post-bulbar stenosis was confirmed and a cystic pneumatosis interesting 60 cm of the ileum was present. A gastro enteroanastomosis was performed with an ileal resection and reestablishment of the continuity. He had no recurrence of the disease. The second patient, a 77 year-old man, was admitted for a surgical treatment of a stenosing bulbar ulcer. On the chest X-ray there were many gaseous formations under the diaphragmatic cupula, characteristic of cystic pneumatosis. The surgical exploration confirmed pyloric stenosis for which a vagotomy and a gastroenteroanastomosis were practised; it was found a cystic pneumatosis interesting one meter of the small intestine, which was not resected. The postoperative course was uneventful. The authors review the literature about this benign disease, which can involve the small intestine in case of duodenal or pyloric stenosis. They stress the usefulness of plain radiography of abdomen demonstrating the presence of characteristic gaseous formations in the subphrenic region. PMID- 1755275 TI - [Isotopic method in the demonstration of diaphragmatic defects in a case of pleural effusion associated with cirrhosis: apropos of a case]. AB - A 62-year-old woman presented with massive right-sided hydrothorax associated with cirrhosis of the liver. Chest scintigraphy after intraperitoneal injection of labelled tracer showed movement of the tracer from the peritoneal to the pleural cavity. Medical therapy and thoracocentesis were successful in this case. PMID- 1755276 TI - [Recurrent peritonitis caused by familial Mediterranean fever]. AB - The authors report a case of Familial Mediterranean Fever (FMF) in a Turkish patient. FMF is characterised by paroxysmal attacks of fever, peritonitis and/or pleuritis or arthritis. FMF is almost exclusively confined to populations of Mediterranean origin and it is often familial. The diagnosis is mainly clinical. Recently an enhanced dopamine beta-hydroxylase (DBH) activity was described as a diagnostic test. We confirmed this in our patient. FMF was successfully treated by chronic colchicine therapy: 1-2 mg daily, which reduced DBH activity to normal levels. PMID- 1755277 TI - [Endoscopic laser treatment for rectosigmoid villous adenoma: factors affecting the results]. PMID- 1755278 TI - [Impaired internal anal sphincters in a subgroup of patients with idiopathic fecal incontinence]. PMID- 1755279 TI - Ultrastructure of the endolymphatic sac in the mouse. AB - The ultrastructure of the endolymphatic sac (ES) in the mouse was examined by light and electron microscopy. This organ was divided into three parts: proximal, intermediate and distal. In the proximal portion of the ES, the epithelium consisted of thin squamous cells. The epithelial cells had acquired basolateral processes, numerous small vesicles and well-developed Golgi apparatus. In the intermediate portion, the epithelium consisted of columnar or cuboidal cells. The epithelial cells could be classified into two types: type I and type II. The type I cells had abundant microvilli, pinocytotic vesicles, vacuoles, multivesicular bodies, lysosomes and mitochondria. The type II cells had fewer numbers of these organelles. A few free-floating cells could be observed in the lumen of this intermediate portion, most of which were macrophages. In the distal portion, the epithelium consisted of squamous or cuboidal cells. The epithelial cells had a few cytoplasmic organelles. In the ultrastructural study, each portion of the mouse ES was found to have a very distinct morphological feature. It was suggested that each of these three portions has a different function. PMID- 1755280 TI - Morphology and histochemistry of the myotendineal junction of the rat calf muscles. Histochemical, immunohistochemical and electron-microscopic study. AB - The macromolecular composition and morphometry of the myotendineal junction (MTJ) of slow-twitch (type 1) and fast-twitch (type 2) muscle fibers were studied in gastrocnemius-soleus-Achilles unit of the rat. Proteoglycans and glycosaminoglycans, type III collagen, fibronectin and laminin could be detected at the myotendineal junction. Due to the membrane folding finger-like processes were seen at the MTJ. The processes of type 1 fibers were greater in size. However, due to the subdivisions the processes of type 2 muscle fibers had a significantly greater surface length per muscle cell diameter than type 1 fibers. The myotendineal endings of both fiber types had a characteristic basal lamina, which was about three times thicker than in the longitudinal site of the same muscle cells. The basal lamina of type 1 fibers at the MTJ was significantly thicker than that of type 2 fibers. PMID- 1755281 TI - A bilateral maxillofacial trunk in man: an extraordinary anomaly of the carotid system of arteries. AB - In a Caucasian male, the maxillary artery (M) bilaterally arose with the facial artery anteromedially from the external carotid artery. On the right side, the M entered the infratemporal fossa between the neck of the mandible and the medial pterygoid muscle, whereas the left M pierced the medial pterygoid muscle, first being covered by the muscle and the angle of the mandible. On both sides, the M ran deep to the inferior head of the lateral pterygoid muscle and the buccal nerve. The right M lay deep to the inferior alveolar, but superficial to the lingual nerve, whereas the left inferior alveolar and lingual nerves had formed two roots, thus encircling the left M. The ascending palatine artery was replaced on both sides by palatine branches of the ascending pharyngeal artery. Since a bilaterial maxillofacial trunk with topographical relations as described herein has not been previously reported in man, the embryology and comparative anatomy of this variation are discussed. PMID- 1755282 TI - Microcirculation of the extra-ocular muscles of rats. A scanning electron microscopic corrosion cast study. AB - Specific researches, employing corrosion casts, were performed on different skeletal muscles, but not on extra-ocular muscles (EOMs). The microvascular bed of EOMs was studied by the corrosion cast technique in the rat. Two histologically and physiologically different layers were present in the EOMs. On the whole, the capillary pattern of EOMs was less dense than in the other skeletal muscles. The EOM orbital layer turned out to have a higher number of transverse anastomoses and tuning-fork divisions than the global layer had. These different microcirculatory patterns can be related with the physiological function and the anatomical situation of the EOMs. PMID- 1755283 TI - Postnatal development of the interstitial cells (palisade cells) of the pars intermedia in the cat pituitary gland. An immunocytochemical and ultrastructural study. AB - The postnatal development of the interstitial agranulated cells (so-called palisade cells) of the pars intermedia in the cat was investigated immunocytochemically and at the ultrastructural level. Since the first postnatal days, a strong vimentin immunoreactivity and a weaker S-100 protein immunoreactivity were detected in the marginal cells lining the pituitary cleft and in the interstitial bipolar cells located within the pars intermedia. No glial fibrillary acidic protein cells have been found in the pars intermedia of any of the animals studied. This immunocytochemical pattern was maintained throughout the postnatal development. Ultrastructurally these cells showed a vast number of cytoplasmic filaments and well-developed junctional complexes. Secretory granules were never seen. In older animals they lined microcavities and microchannels where they project microvilli and present pinocytotic vesicles on their apical surface. No transitional forms between these cells and granulated secretory cells were found. There is a large number of axons and synaptic endings in contact with the granulated secretory cells. From our findings we guess that palisade cells are not a glial derivative, but they may share a common origin with secretory granulated cells. PMID- 1755284 TI - [Anatomical aspects of the arteria inferior posterior cerebelli for posterior fossa surgery]. AB - As the arteria inferior posterior cerebelli sometimes causes surprises of grave consequence at surgical approaches, its origin and course had to be described in detail. For this aim, we especially considered the local relationships of this artery with the medulla oblongata and the cranial nerves of the posterior fossa. Branches of the a. inferior posterior cerebelli supplying the medulla oblongata have been noticed in relation to the arterial supply of the medulla oblongata by corresponding vessels and the aa. spinales lateralis and posterior with special reference to all the possible collateralizations. PMID- 1755285 TI - Relationships between bone and skin atrophies during aging. AB - Bone mineral density (BMD) was measured in 133 female subjects (age: 61.7 +/- 16.3 years) by dual energy X-ray absorptiometry (DEXA). Vertebral bone mineral density (BMD; L1-L4) and BMD of the whole upper femoral extremity were taken into account. In addition, skinfold thickness was measured with a callipers on the dorsum of the nondominant hand. A significant negative correlation was found between skinfold thickness and age (r = -0.623, p less than 0.0001). Both vertebral and femoral BMD decreased with age and the slopes were similar to those observed by other authors. Skinfold thickness was significantly correlated with vertebral (r = 0.364, p less than 0.0001) and femoral BMD (r = 0.486, p less than 0.0001). Skin and bone are connective tissues whose extracellular matrix mainly contains type I collagen. It is postulated that age-related skin atrophy and bone atrophy have a common genetic mechanism. Skinfold thickness measurement may help in defining the women at risk for osteoporotic bone fractures who should be referred for a DEXA examination. PMID- 1755286 TI - Changes in lectin-binding patterns during late fetal development of the rat colon. AB - Lectin-binding and histochemical studies were integrated with a morphological description of colon development in rat fetuses to determine whether changes in glycoprotein sugars could be identified with stages of colon organogenesis. At 16 days gestation the colon consisted of a minute lumen surrounded by 3-5 layers of cuboidal, stratified epithelium, a basement membrane and undifferentiated mesenchyme. As development proceeded, epithelial spaces eventually fused with the main lumen, and fingers of mesenchyme, with a basement membrane and epithelial mantle, formed the walls of crypts lined with simple to stratified columnar cells. Goblet cells and mucin production appeared only on the 20th-21st day of gestation. Mesenchyme differentiation to a circular muscle band, the prospective tunica muscularis, occurred on days 17-18, and vascularization of the lamina propria was first detected on day 19. Wheat germ agglutinin (WGA) lectin bound avidly to sugar residues in the mesenchyme matrix from day 16 but weakened as the tissue differentiated, particularly into smooth muscle. Alcian blue staining of the matrix, also weakening with time, confirmed the sialic acid nature of binding sites for WGA on matrix acid mucopolysaccharides. Under controlled conditions, WGA also detected N-acetylglucosamine-binding sites on brush borders as they developed on the apical surface of primitive enterocytes. Ulex lectin bound to fucose residues of Alcian-blue-positive, PAS-positive mucin from the first appearance of goblet cells. Concanavalin A and glycine max lectins bound only to blood group substances on both nucleated red cells between days 16 and 19 and anucleate red cells from day 19.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755287 TI - Growth allometry of the myocardium in human embryos (from stages 15 to 23). AB - The relative growth of the myocardium was studied in 27 staged human embryos (Carnegie stages). The volume of the myocardium was determined for each embryo according to Cavalieri's principle (by using point-counting planimetry to determine the area of the profiles of the myocardium). The volume of the myocardium (variable Y) was correlated to embryonic crown-rump length (variable X in millimeters) and age (in days). The bivariate allometric equation was used as Y = aXb. The scatterplot was discontinuous, presenting two trends during the postsomitic period. The first part was composed of embryos staged from stages 15 to 20, and the second part by embryos staged from stages 21 to 23. The breakpoint between these different trends was found at the level of stage 20 (embryo of 22 mm in crown-rump length and age nearly of 52 days). From stages 15 to 20, the growth rate of the myocardium was allometrically negative. On the other hand, from stages 21 to 23 this growth rate was moderately allometrically positive. These differences in growth of the myocardium were analyzed and, at least partially, might be due to the functional circulatory increase in the peripheral vascular bed in correlation to the cardiac hemodynamic demand required at the end of the embryonic period proper. PMID- 1755288 TI - Histochemical localization of carbonic anhydrase in the testis and epididymis of the boar. AB - The testis and epididymis of sexually mature, fertile boars were studied for localization of carbonic anhydrase (CA) using a cobalt precipitation technique. In the testis, cytoplasmic CA was found in the Sertoli cells and in the capillaries surrounding the seminiferous tubules. The epididymal duct was divided into initial, middle and terminal segments, and regional differences in CA activity were observed. The cell membranes of the basal cells were stained in the initial and middle segments. Strong cytoplasmic CA staining was present only in the apical cells in the initial and middle segments. The basolateral cell membranes were stained in the principal cells of the terminal segment and the ductus deferens. As a rule the capillaries surrounding the epididymal duct were unstained. The enzyme, specifically localized in regions of the male genitalia acting as sperm reservoirs, might be related to the quiescence of the stored spermatozoa by influencing the acid-base status of the epididymal fluid. PMID- 1755289 TI - Ultrastructural studies on the barrier properties of the paraganglia in the rat recurrent laryngeal nerve. AB - The permeability of blood capillaries in the paraganglia of the rat recurrent laryngeal nerve (RLN) was investigated by employing the ionic lanthanum tracer at ultrastructural level. Two types of blood capillaries, namely, fenestrated and nonfenestrated types, were observed in the rat RLN and its associated paraganglia (RLN paraganglia). A preferential distribution of fenestrated capillaries in the RLN paraganglia was noted. Nonfenestrated capillaries were distributed in the area of RLN devoid of paraganglia. Minute aberrant ganglia consisting of 4-8 neurons were frequently encountered in the rat RLN near the paraganglia. The capillaries in these neuronal areas were also nonfenestrated. The lanthanum tracer was limited within the vascular lumen, but not in the extravascular space, in the RLN proper and in the area of RLN paraganglia where the neurons were identified. In the RLN paraganglia, the tracer was located in the vascular lumen, extravascular space, periaxonal space of nerve fibers, and the intercellular space of the RLN paraganglionic cells. We concluded that (1) a blood-nerve barrier and a blood-ganglion (or blood-neuron) barrier exist in the area of RLN devoid of paraganglia, and (2) blood-paraganglion barrier and blood-nerve barrier were lacking in the rat RLN paraganglia. PMID- 1755290 TI - Effects of lactation on the border zone formation in the female mastomys (Praomys coucha) adrenal cortex. AB - Adrenocortical zonation and especially border zone formation were investigated in relation to reproduction in female mastomys of the wild-colored inbred strain (MWC). The adrenal weight and the whole thickness of the cortex remained relatively constant throughout pregnancy, delivery and lactation. During pregnancy the zona fasciculata increased, but the z. reticularis decreased in thickness. The border zone between the z. fasciculata and the z. reticularis thickened 2-fold during pregnancy and further 2-fold during lactation. This zone was composed of vacuolated cell layers and nodules in females with a normal reproductive career. In young virgins this zone was barely identified by the presence of a few highly vacuolated cells. These cells became prominent during pregnancy and lactation. During lactation two types of cell aggregations, distinguishable by their stainability, vacuolation, localization and cellularity, appeared in the thickened border zone. The nodules first appeared within the z. reticularis after lactation. Neither thickening of both border zone and z. fasciculata nor formation of nodules occurred when lactation was interrupted after delivery. Thus, the changes in the female MWC adrenal, above all the appearance of nodules, seemed to be more dependent upon lactation than pregnancy. The vacuolated cells and the nodules might originate from the thickened z. fasciculata and the thinned z. reticularis, respectively, by the specific metamorphosis of the cells adjacent to the border zone. Their fusion and induction of fibrous tissue migration may result in the wider border zone. PMID- 1755291 TI - Configurational and volumetric changes of the early prenatal human cerebellar dentate nucleus. AB - The three-dimensional configurational and volumetric changes of the human dentate nucleus (DN) during intrauterine life were examined in 11 fetuses (11 to 27-28 weeks of gestation). During intrauterine life, the dentate nuclear profile successively passes through the pongid, cercopithecus and prosimian phases of configuration. The smooth, elongated, crescent-shaped DN of 11 weeks lies along a dorsal-ventral axis. A 45 degrees clockwise shift in the position of the nucleus changes the axis to dorsomedial-ventrolateral at 14-15 weeks, which is maintained in subsequent ages. The formation of gyri is preceded by a thinning of the substantia grisea. This begins at 17-18 weeks in the dorso-medial region of the DN. Gyri first make their appearance at 24-25 weeks. The DN of 27-28 weeks resembles the adult human DN. Two regions are discernible at this stage--a microgyric, magnocellular region and a macrogyric, parvocellular region. The DN volume increases with increasing gestational age. Between 14-15, 19-20 and 24-25 weeks the volumetric increase is statistically significant. This is simultaneously accompanied by a modification of the configuration of the DN. PMID- 1755293 TI - Proceedings and dissertation abstracts. PMID- 1755292 TI - Ultrastructural changes in rat colorectal epithelium and tumors after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and secondary bile acids. AB - Transmission electron microscopy (TEM) was used to study ultrastructural changes that accompanied the tumorous transformation of the descending rat colon epithelial cells, following short treatment with a direct carcinogen, N-methyl-N' nitro-N-nitrosoguanidine (MNNG), with subsequent prolonged treatment with secondary bile acids, lithocholic (LCA) and deoxycholic (DCA), which enhanced tumor formation. Colon epithelial cells after long treatment with bile acids alone were characterized by the presence of an irregular nuclear membrane, ring shaped rough endoplasmic reticulum (RER), collagen-like tonofilaments and membrane-bound mucous vacuoles. Tumor cells which developed following treatment with MNNG alone were characterized by the irregular shape of the nuclear membrane and, sometimes, by polynuclei, accumulation of large amounts of mitochondria, loss of cell-cell contacts and by endocytosis of the cell membrane. After combined treatment with MNNG and LCA, many mitochondria lost their membranous envelope; in the cytoplasm many collagen-like tonofilaments, ring-shaped RER and many free ribosomes were present. After treatment with MNNG and DCA, many polysomes were found in the cytoplasm. It was apparent that treatment with MNNG alone caused the development of adenocarcinoma-like tumors, while additional treatment with secondary bile acids significantly enhanced these changes, which were accompanied by the development of atypia and anaplasia of epithelial cells, with many irregularities in intracellular organization. PMID- 1755294 TI - Sodium and potassium in red blood cells of premature infants during the first few days: risk of hyperkalaemia. AB - Erythrocyte sodium and potassium were studied in 64 newborn infants including 21 very low birthweight infants (birthweight less than 1500 g) during the first three days after birth. Erythrocyte sodium showed a positive correlation with gestational age (r = 0.63, p less than 0.01) and birthweight (r = 0.66, p less than 0.01). Erythrocyte potassium was negatively correlated with birthweight (r = -0.33, p less than 0.05). The Na/K ratio in red blood cells showed a positive correlation with gestational age (r = 0.60, p less than 0.01) and birthweight (r = 0.65, p less than 0.01). In VLBW infants plasma potassium rose significantly (p less than 0.01) from 0-6 h to 12-30 h and decreased from 12-30 h to 30-60 h (p less than 0.05). Erythrocyte potassium decreased slightly from 0-6 h to 12-30 h, but not significantly. A new finding that "more immature infants have higher potassium and lower sodium concentration in RBC" may suggest a potential risk of hyperkalaemia in tiny infants. PMID- 1755295 TI - Cerebral blood flow velocity and cardiac output in infants of insulin-dependent diabetic mothers. AB - Cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries were investigated in eight large-for-date infants of insulin-dependent diabetic mothers and 12 healthy term infants during the first four days of life using two-dimensional/pulsed Doppler ultrasound. Temporal mean flow velocity was used as an indicator of changes in cerebral blood flow. Six of the eight infants of diabetic mothers had ventricular septal hypertrophy with reduced cardiac outputs and stroke volumes. Mean flow velocity in both cerebral vessels showed a comparable pattern in both groups throughout the study period and was independent of mean arterial pressure, suggesting unaltered cerebral hemodynamics in the infants of diabetic mothers. PMID- 1755297 TI - Roentgen stereophotogrammetric short-term analysis of growth rate in children operated for Crohn's disease. AB - Roentgen stereophotogrammetry is a new method for short term analysis of growth rate. Growth is measured over the growth zone in the distal fibula and is a fraction of the total statural growth. Normal growth rate in the distal fibula is about 15 micrograms/day at a total growth rate of 5 cm/year. The method was used to follow growth six months before and six months after surgery in six growth retarded children with Crohn's disease. Growth rate increased significantly (p less than 0.01) within three months after surgery from 5.8 microns/day before operation to 15.8 microns/day three months after operation and six months postoperatively had reached 18.0 micron/day. Improved growth could be recorded as early as four weeks after operation. The Roentgen stereophotogrammetric analysis (RSA) gives a unique possibility to follow short-term changes in growth rate in children with disturbed growth and to use growth rate as a quick assessment of response. PMID- 1755296 TI - Ampicillin-aminoglycoside combinations as initial treatment for neonatal septicaemia or meningitis. A retrospective evaluation of 12 years' experience. AB - In a retrospective study covering the years 1975-1986, 341 episodes of invasive infections in 338 newborn infants were evaluated. Of the 365 pathogens isolated from blood and/or cerebrospinal fluid, 91% were sensitive to either ampicillin or aminoglycosides or both. Ampicillin resistance was mainly found in very low and low birthweight infants with late-onset infections, in which aerobic Gram negative rods were common pathogens. In contrast, aminoglycoside resistance was common in early-onset infections, due to the dominance of group B streptococcal infections. The ampicillin-aminoglycoside combination had been given as initial treatment in 189 cases of septicaemia or meningitis. Treatment failed in 36 infections (20%), although all organisms were sensitive to one or both antibiotics. Treatment failed in 6 of 34 patients with meningitis but the failure was not related to ampicillin or aminoglycoside resistance. In conclusion, both in vitro and clinical results show that the ampicillin-aminoglycoside combination can be used as initial treatment of invasive infections in neonates. PMID- 1755298 TI - Treatment for stage III-IV neuroblastoma patients: initial response to chemotherapy evaluated by biochemical parameters. AB - Fourteen patients with stage III-IV neuroblastoma were treated with alternating combination chemotherapy consisting of (a) VP16/cisplatin and (b) doxorubicin/vincristine/cyclophosphamide. The initial response to induction chemotherapy, especially to VP16/cisplatin was evaluated by determining t 1/2 for urinary vanillylmandelic acid (VMA), homovanillic acid and serum neuron specific enolase (NSE). The period prior to normalization of these parameters was also determined. The patients could be classified as 7 rapid responders, with less than 3 weeks of t 1/2 VMA, or t 1/2 NSE, and 7 slow responders longer than 4 weeks of t 1/2 VMA. An analysis of the data indicates that an initial rapid response correlated with subsequent high complete response rate, but did not necessarily predict better prognosis in these patients. PMID- 1755299 TI - Phenotypes of peripheral blood lymphocytes during acute hepatitis A. AB - We investigated peripheral blood lymphocyte phenotypes of 74 patients at weekly intervals during the course of acute hepatitis A. In the second week after onset of jaundice, a significant elevation of total lymphocytes was observed (4,096 X 10(6) +/- 1,003 X 10(6)/l vs. controls 3,038 X 10(6) +/- 1,208 X 10(6)/l, p less than 0.005). However, no change in the relative percentage of B-cells (CD20+), T cells (CD3+ or CD2+), or T-cell subpopulations (CD4+ helper cells and CD8+ suppressor cells) could be demonstrated during the course of the disease. Activated T-cells (CD3+ DR+) were elevated during the first week (204 X 10(6) +/- 134 X 10(6)l vs. normal 91 X 10(6) +/- 54 X 10(6)/l, p less than 0.005) and during the second week (202 X 10(6) +/- 82 X 10(6)/l, p less than 0.0005) after onset of disease and returned to normal values until the third week. Cells expressing phenotypes of lymphocytes capable of exerting non-MHC-restricted cellular cytotoxicity, i.e. Natural Killer cell activity (CD57+, CD16+, and CD56+) were significantly elevated in percentage in the first week of disease, as compared to controls (CD57: 14.5 +/- 7.0% vs. 9.3 +/- 5.8%, p less than 0.05; CD16: 13.4 +/- 7.3 vs. 9.5 +/- 5.1%, p less than 0.05; CD56: 10.5 +/- 3.5% vs. 8.0 +/- 1.5%, p less than 0.005). Also the absolute numbers of these lymphocyte subpopulations were found to be elevated during the first and second week. The increase in NK cells in the initial phase of acute hepatitis A suggests an important role of these cells in the first line of defence in this disease. PMID- 1755300 TI - Effect of metabolic control on serum protein concentrations in diabetes. AB - Serum albumin, transferrin, transthyretin (prealbumin), and retinol binding protein concentrations were determined in 74 children with insulin-dependent diabetes mellitus before and after a 10-day camp session during which blood glucose concentrations were controlled. Initial concentrations of albumin and transferrin in the subjects were not different from those in 21 children and adults without diabetes, and did not change during the study period. Transthyretin and retinol binding protein concentrations were lower in subjects with diabetes than in the control population, and increased from 182 +/- 49 mg/l and 42.5 +/- 13.4 mg/l to 232 +/- 71 mg/l and 47.2 +/- 13.5 mg/l, respectively. We observed correlations between the changes in transferrin, transthyretin, and retinol binding protein. Although reductions in glycated albumin and transferrin indicated improvement in blood glucose control, there was no correlation between changes in the glycated markers and the concentrations of serum transport proteins. Thus, serum protein concentrations were influenced by the metabolic control of diabetes, but did not directly reflect blood glucose. PMID- 1755301 TI - Monitoring of drug prescriptions for children in the county of Jamtland and Sweden as a whole in 1977-1987. AB - One individual-based (Jamtland) and one population-based (Sweden) monitoring system provided information on the prescription sales of drugs for children in ambulatory care. The overall prescription rate decreased between 1977 and 1987 and it was 20-25% lower in Jamtland than in Sweden as a whole. Antibiotics, drugs for ear, nose and throat diseases and respiratory drugs accounted for three out of four prescriptions. Penicillin V dominated among antibiotics and the prescription rate was stable whereas that of other antibiotics increased. During their first year of life one out of ten children in Jamtland had at least one prescription of antibiotics, during their first five years three out of four children. Prescribing of decongestants, especially systemic, decreased during the study period whereas that of anti-asthmatics increased, partly due to the non approved use of these drugs for common cough. The results from our study underline the need for pharmaco-epidemiological studies linking prescription data to clinical data in order to answer questions on the rational of present drug treatment practices. PMID- 1755302 TI - Menarche 1990 in Stockholm schoolgirls. PMID- 1755303 TI - Linear growth in Sotos syndrome. PMID- 1755304 TI - Intolerance to casein hydrolysate formula. Clinical aspects. PMID- 1755305 TI - Persistence of protein loss in acute diarrhoea. A follow-up study by faecal alpha 1-antitrypsin measurement. PMID- 1755306 TI - Calcium-induced constipation in a prepubescent boy. PMID- 1755307 TI - Late haemorrhagic disease in Sweden 1987-89. PMID- 1755308 TI - Antitussives in the treatment of acute transient cough in children. PMID- 1755309 TI - Oral absorption of amoxicillin in Ethiopian children with respiratory symptoms and different nutritional status. PMID- 1755310 TI - Thrombocytopenic purpura during the incubation of hepatitis B. AB - A 6-year-old girl presented with acute thrombocytopenic purpura. Hepatitis B surface antigenaemia was present at the time of this illness, and 8 weeks later she developed acute icteric hepatitis B. Screening for hepatitis B virus should be considered in children with apparently idiopathic thrombocytopenic purpura. PMID- 1755311 TI - Twenty-nail dystrophy associated with hematologic abnormalities. AB - This report describes a 15 1/2 year old white male with twenty-nail dystrophy who has had recurrent episodes of immune thrombocytopenic purpura, autoimmune hemolytic anemia, and mild depression of immunoglobulin levels. The concurrence of these events suggests that each shares a common pathophysiologic mechanism, possibly an autoimmune process. PMID- 1755312 TI - Congenital hypothyroidism and cystic fibrosis. AB - We report a case of dysgenetic congenital hypothyroidism associated with cystic fibrosis. Impaired exocrine pancreatic secretion and/or transit abnormalities secondary to the treatment of meconium ileus resulted in decreased absorption of L-thyroxine and difficulties in management of hypothyroidism. PMID- 1755313 TI - A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism. AB - We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature. PMID- 1755314 TI - Intestinal absorption of D (+) xylose in newborns. PMID- 1755315 TI - Pathological aspects of radiofrequency catheter ablation of the canine atrioventricular node and bundle of His. With special reference to chronic incomplete atrioventricular block. AB - Radiofrequency catheter ablation of the atrioventricular (AV) node or bundle of His was performed in 12 adult mongrel dogs. The aim was to create chronic incomplete AV block (first- and second-degree AV block) and to examine the histopathology of the ablated lesions. However, the late electrophysiological results (2-4 weeks follow-up) were various: normal in 2 dogs, mild PR prolongation (less than 50%) in 2 dogs, first-degree AV block (PR prolongation greater than or equal to 50%) in 2 dogs, second-degree AV block in 2 dogs, complete AV block in 4 dogs. The maximally ablated area (%) of the atrioventricular conduction system in serial histologic sections from dogs with these conditions was 69%, 75%, 89.5%, 95% and 99.5%, respectively. The number of intact conduction cells at the maximally ablated site varied from 6 to 30 in the four cases of incomplete AV block. The mean ablated volume (%) of either the AV node or penetrating His bundle correlated roughly with the degree of AV block. The ablated lesions were well demarcated and almost replaced by dense fibrous tissue at 4 weeks. Interruption (3 dogs) or thinning (1 dog) of the endocardial elastic lamellae was detected, in association with endocardial thickening (mean 913 microns). Endocardial thrombi were found in 3 dogs (2 fresh, 1 organized). We conclude that radiofrequency catheter ablation does not cause severe complicated lesions. Several possible conditions for creating chronic incomplete AV block are discussed. PMID- 1755316 TI - Monoclonal antibody against bone marrow stromal cells. Its production and characterization. AB - Bone marrow stromal cells play an essential role in the proliferation and differentiation of hematopoietic stem cells (1, 2). As a means of analyzing of the bone marrow microenvironment immunohistochemically, we attempted to produce a rat monoclonal antibody against the murine preadipocyte line H-1 derived from long-term bone marrow culture (LTBMC) of C57BL/6 mice (3, 4). A newly established monoclonal antibody, designated R4-A9, was obtained from a hybridoma prepared by fusion of Y.B2/3.0Ag20(YO) rat myeloma cells with spleen cells of LEW rats immunized with H-1 cells. The immunofluorescence of live H-1 cells showed that the antigen reacting with this antibody was strongly expressed on the cell surface. The specificity of R4-A9 was assessed immunohistochemically on frozen sections of various tissues from normal adult mice. R4-A9 demonstrated specificity for hematopoietic stroma in bone marrow and spleen. No staining was observed in thymus, lymph nodes or other tissues examined, with the exception of Leydig cells in the testis and the endothelium of small arteries in several organs. Detailed immunohistochemical observations at both the light microscopy and electron microscopy level showed that R4-A9 selectively reacted with the sinusoidal endothelium, perisinusoidal adventitial cells (5) (adventitial reticular cells (6] and intersinusoidal reticular cells (5) and the reticular cells of the splenic red pulp. These findings indicate that reticular cells and the endothelium of the bone marrow possess the common cell surface molecules recognized by R4-A9. SDS-PAGE analysis showed that R4-A9-immunoprecipitated proteins had a molecular mass of 100 kDa under reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755317 TI - Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line. AB - A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma. PMID- 1755318 TI - A histological, ultrastructural and immunohistochemical study of superficial temporal arteries and middle meningeal arteries in moyamoya disease. AB - Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro-temporal arterio-synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (EI). The EI had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra- and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG-, IgM-, and C3-positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occurred in these arteries. PMID- 1755319 TI - Abnormal granulopoiesis of leukemic cells with basophil/mast cell features. Cytochemical and ultrastructural observations. AB - We have carried out cytochemical and ultrastructural examination of human leukemic cells showing basophil/mast cell features derived from patients with acute myelogenous leukemia or basophilic crisis in chronic myelogenous leukemia. Leukemic cells in each case initially showed metachromasia with toluidine blue and various degrees of positivity for astra blue. Other cytochemical results showed considerable variety among cases. The number of granules increased in short-term culture in every case. Ultrastructurally, small membrane-bound granules with or without myelinoid bodies or glycogen particles were present in immature blasts, followed by production of other granule types. In some cases, leukemic cells before and after liquid culture contained the typical basophil granules with or without myelinoid bodies, but the matrix was more loose than normal. Granules showing whorl or scroll matrix profiles, which were typical for mast cells, were present in two cases. In one case, immature leukemic cells contained theta granules, and some mature forms after short-term culture contained typical basophil/mast cell granules as well as theta granules. Leukemic cells occasionally contained multivesicular granules predominantly. These results indicate that leukemic cells with basophil/mast cell features show a heterogeneous configuration and contain abnormal granules differing from normal ones. This abnormal granulopoiesis may be attributable to the results of leukemic events and may be a hallmark for recognition of leukemic basophils/mast cells. PMID- 1755320 TI - Giant cell fibroblastoma. A case report and immunohistochemical comparison with ten cases of dermatofibrosarcoma protuberans. AB - A 7-year-old boy with giant cell fibroblastoma (GCF) of the skin and subcutaneous tissue of the right chest wall is described. To date, the histogenesis of GCF has not been clarified. The reason for the diversity of immunohistochemical data among various authors may be because the specimens studied were from only part of the lesion, or reduction of antigenicity through the preparation process. However, our findings based on studies of many specimens from various parts of the tumor for accurate immunohistochemical evaluation suggest that GCF may be a myofibrohistiocytic tumor. Recently, the suggestion that GCF is a juvenile form of dermatofibrosarcoma protuberans (DFSP) has been reported. In addition to the present case, we performed immunohistochemical examination of 10 cases of definitely diagnosed DFSP for comparison. The immunohistochemical characteristics of these two neoplasms were concordant. However, from clinical and morphological viewpoints, it seems premature to recognize GCF as a juvenile form of DFSP. PMID- 1755321 TI - Intestinal mucormycosis in a hemodialysis patient treated with desferrioxamine. AB - A case of fatal intestinal mucormycosis in a 57-year-old female hemodialysis patient who had received desferrioxamine (DFO) for aluminum overload is reported. The focus of fungal infection was not found until the intestine had been resected surgically. DFO is being used with increased frequency in dialysis patients to treat aluminum or iron overload. Recently a possible link between DFO therapy and mucormycosis has been suggested. In the management of hemodialysis patients, the potential risk of mucormycosis with DFO therapy should be considered. PMID- 1755322 TI - Necrotizing fasciitis rapidly diagnosed by aspiration cytology. AB - A case of necrotizing fasciitis caused by beta-hemolytic streptococci is reported. A 66-year-old man was admitted because of pain and swelling in the right buttock. Rapid application of aspiration cytology made it possible to diagnose necrotizing fasciitis with bacterial infection. Unfortunately, however, the patient died of cardiac arrest due to hyperpotassemia 11 h after admission. Mortality from this disease is most often related to failure in recognizing it early. Rapid diagnosis and early treatment is mandatory in order to save the patients' life. We emphasize the usefulness of rapid aspiration cytology, despite the unfortunate outcome in the present case. PMID- 1755323 TI - In memoriam Miklos Jancso (1903-1966). PMID- 1755324 TI - Effect of benzopyrone derivatives on simultaneously induced croton oil ear oedema and carrageenin paw oedema in rats. AB - Carrageenin paw oedema and croton oil ear oedema induced simultaneously in rats are inhibited in a dose-dependent manner and to statistically significant degrees by lipoxygenase- and cyclooxygenase-blocker flavonoids (diosmin, fisetin, quercetin, myricetin, galangin, sophoricoside, hesperidin-methylchalcone, oligomeric procyanidin, anthocyanidins (delphinidin, pelargonidin], and the prostaglandin antagonist polyphloretin phosphate and di-4-phloretin phosphate. Outstanding anti-inflammatory effects are displayed by myricetin and delphinidin, which contain vicinal hydroxy groups in ring B. The results confirm the importance of hydroxy group substitution in ring B. The most effective of the examined substances proved to be the prostaglandin antagonist di-4-phloretin phosphate. PMID- 1755325 TI - A possible pathomechanism of the idiopathic cold contact urticaria. AB - Urtica is characterized by an erythematous wheal surrounded by a flare and is frequently caused by physical agents (e.g. cold). The exact mechanism and mediators involved in the mechanism of physical urticaria are not known. This study of the role of the neurogenic factors in cold urticaria showed, that local capsaicin treatment (desensitization) of the skin in patients with cold urticaria resulted in the abolition of whealing in response to cold. This result suggests that C-fibers might play an important role in the pathomechanism of idiopathic contact cold urticaria. PMID- 1755326 TI - Diabetes-induced decreased sensitivity to blocking drugs of autonomic ganglia and motor endplates: new hypothesis for an old observation. PMID- 1755327 TI - Vaccina treatment in some hospital infections. AB - Phenol-treated vaccine was prepared from the usual hospital strains and patients with colorectal cancer were immunized intramuscularly 7-10 days prior to the operation. The efficiency of the vaccine treatment was judged by the incidence of wound infections. The best results were obtained in patients whose previously estimated immunoreactivity was strong or normal. Immunospecificity could not be detected in the above treatment. The frequent and inappropriate use of antibiotics in hospitals increases the number of resistant hospital bacterial strains. Apart from Staphylococci and Streptococci, different Gram-negatives- such as Klebsiella, Serratia, Pseudomonas, Proteus and E. coli strains--have been found in the hospitals and in the patients. Due to the resistance, it is difficult to find antibiotics against them. This fact puts forward the possibility of immunization especially by vaccination. PMID- 1755328 TI - Prevention of anaphylactic death by macrophage blockade. AB - Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study the effect of macrophage blockade induced by gadolinium chloride (GdCl3) on anaphylactic shock was investigated. Our observations show that GdCl3 prevents the lethal anaphylactic shock of mice sensitized to ovalbumin. GdCl3 given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 90% survival, compared to the 43% survival in the control group. The same dose of this rare earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containing Bordetella pertussis vaccine, and the symptoms of anaphylaxis including the accumulation of 5-hydroxytryptamine in the liver. Our results suggest that macrophages play an important role in anaphylaxis. PMID- 1755329 TI - Experimental and clinicopharmacological study of rectal absorption of chloroquine. AB - Chloroquine administered as a rectal suppository is resorbed both in rabbits and human volunteers. Although the chloroquine blood level in rabbit is proportional to the dose investigated, the human rectal mucosa has a limited absorption capacity of chloroquine being saturated at 15 mg/kg dose. In spite of this saturation character the chloroquine applied as rectal suppository may be a suitable formulation to treat or prevent the malarial infection for persons unable to take the drug perorally, e.g. children, or unconscious adults, or persons suffering with GI complaints after swallowing the chloroquine tablet. PMID- 1755330 TI - Effects of simulated ischaemia on the electrical activity of ventricular myocardium in the presence of antiarrhythmic drugs. AB - The effects of a nutrient solution simulating the 'ischaemic milieu' (combined hyperkalaemia, hypoxia and acidosis) on the electrical activity of rabbit isolated ventricular myocardium were examined in the absence and presence of antiarrhythmic drugs. In such a simulated ischaemia the resting membrane potential, the rate of depolarization (Vmax) and the action potential duration (APD) were all diminished with a resultant decrease in conduction and a shortening of the effective refractory period (ERP). Sotalol, a Class 3 antiarrhythmic drug (5 x 10(-6)-10(-5) M/l) afforded a marked protection against the "ischaemic" abbreviation of the ERP and APD. To a much lesser extent, the same applied to propafenone, a predominantly Class 1C antidysrhythmic agent (1.65 3.3 x 10(-6) M/l). The 'ischaemia'-induced depression of Vmax was increased considerably by propafenone and diminished slightly by sotalol. The results are in keeping with the efficacy of propafenone and sotalol in ventricular arrhythmias of ischaemic origin and also with the proposal that the major mechanism by which propafenone inhibits postinfarction ventricular arrhythmias is a further depression of ischaemic myocardial cells resulting in conduction block of the reentrant wave front. PMID- 1755331 TI - Effect of Ca2+ antagonists on isolated rabbit detrusor muscle. AB - Ca(2+)-antagonists change the contractility of isolated detrusor smooth muscle of rabbit influencing the translocation of intra- and extra-cellular Ca2+. This observation might be of clinical importance in the treatment of disorders of urinary bladder function. During field stimulation of different segments of isolated rabbit bladder it was found that the specific Ca(2+)-antagonist nifedipine and verapamil and the non-selective Ca(2+)-antagonist fendiline, prenylamine and cinnarizine blocked the contractions induced by field stimulus to different extent, which decreased from the bladder towards the bladder base (fundus). The highest rate of blocking effect was produced by nifedipine followed by verapamil, prenylamine and fendiline, respectively. Cinnarizine exerted the lowest effect. The change in amplitude and frequency of spontaneous peristalsis was similar in its tendency to the blockade of the field stimulus induced contraction. PMID- 1755332 TI - Pharmacogenetically hazardous drugs: a proposed new scoring method. AB - Similar doses of a drug given to different individuals can result in widely disparate plasma concentrations and hence effects. Beside intraindividual differences also inter-ethnic differences of drug response must be taken into consideration. Both inter-individual and inter-ethnic variations of drug response are mostly related to genetic factors (polymorphism) involved in drug metabolism and kinetics. The farmacogenetic disorders involved clinically result in pharmacogenetic side effects. In order to avoid pharmacogenetic side effects, beside phenotyping of the patients, selection of drugs subjected to different pharmacogenetic disorders may be of great clinical importance. Therefore, a scoring method was carried out for the selection of pharmacogenetically hazardous drugs. With regard to both genetic and environmental factors influencing the drug response, 140 suspicious drugs were studied and classified with the method. Eighteen was the maximum point value for genetic and 12 for contributing factors involved, so 30 was the maximum point number in each drug studied. Out of 140 substances 50 drugs (qualified with 20 points or more) proved to be hazardous in different pharmacogenetic disorders, among them several widely used agents, e.g. Diazepam, Isoniazid, Phenytoin, Warfarin, Quinidine, Tolbutamide, etc. The article sums up the findings in a Table and comments them. This scoring method may be useful in drug safety and preventive medicine. PMID- 1755333 TI - Abrogation of neonatally induced permanent transplantation tolerance in mice: quantitative aspects. AB - Neonatal transplantation tolerance was induced in CBA (H-2k) mice by the intravenous injection of 20 million (CBAxA)F1 spleen cells to the transplantation antigens of the A mouse strain. Those mice which carried an A (H-2a) skin allograft without any sign of rejection for at least 120 days, were considered to be permanently tolerant and were selected for further experiments. Abrogation of permanent transplantation tolerance was achieved by injecting the tolerant mice with different doses (50, 100 and 200 millions, respectively) of normal syngeneic (CBA) lymphoid (spleen) cells. Dynamics of the rejection of the test skin allografts tolerated so far revealed well reproducible dose-response curves. Further groups of tolerant CBA mice were given 10, 50, 100, or 200 million "sensitized" (G + 16) CBA spleen cells: "sensitization" by A-skin allografting was performed 16 days before. The sensitized spleen cells abolished the state of tolerance more vigorously and effectively than the normal CBA spleen cells did. In a third group of experiments, the abrogating capacity of 50 million sensitized CBA spleen cells 16, 120, 240, or 360 days after sensitization was compared. The efficacy of the sensitized cells in abolishing the state of tolerance decreased continuously, but, even 360 days after sensitization a remarkably strong immunologic memory was demonstrable. The excellent quantitative correlations found between the number of the injected lymphoid cells and the dynamics of the abrogation of tolerance offer a highly promising new possibility for studying the immunological activity, the immunologic memory, etc., of the different lymphoid cell (sub)populations in performing the transplantation immune reactions. PMID- 1755334 TI - Analysis of galactosyltransferase activity in rat gastric mucosa using crude mucosal homogenate. AB - Mucus glycoprotein is one of the major components of gastric mucus which plays an important role in mucosal defensive mechanisms as a mucus-bicarbonate barrier. Analysis of the mucus glycoprotein synthesis is a useful tool for evaluating gastric mucosal defensive factors. UDP-galactosyltransferase (UDP-Gal-T) is one of the regulating enzymes for the synthesis of the mucus glycoprotein. In the present paper, we studied assay methods for UDP-Gal-T activity in rat gastric mucosa using radiolabeled UDP-galactose and two different kinds of acceptor proteins, namely ovomucoid and asialomucin, and analyzed effects of antisecretory agents on the UDP-Gal-T activity. We used crude supernatants of homogenized scrapings of the fundic part of rat stomach as an enzyme preparation and determined optimal conditions. In each acceptor, Mn2+ and the non-ionic detergent Triton X-100 were required for the enzyme activity. With each acceptor molecule, the type of glycosidic linkages of galactose was beta-type linkage. With asialomucin as an acceptor, UDP-Gal-T activities of rat gastric mucosa decreased after intraperitoneal administration of antisecretory agents, while change of the enzyme activity was not observed with ovomucoid as an acceptor. PMID- 1755335 TI - A monoclonal antibody which recognizes the inner and outer segments of the photoreceptor cells in the vertebrate retina. AB - A monoclonal antibody (MAb-1E7), generated against bovine retinal homogenate, labeled the outer and inner segment layers of the vertebrate retina. Immuno electron microscopic observation clearly demonstrated that antigen(s) bound by MAb-1E7 was localized in the cell membrane of the outer segment and the distal portion of the inner segment. Western blot analysis revealed that MAb-1E7 recognized 40 kD- and 27 kD-polypeptides. Mouse retina with hereditary photoreceptor degeneration (C3H/He and CBA strains) did not involve the MAb-1E7 immunoreactive structures. The present immunocytochemical observation demonstrated that MAb-1E7 was highly specific to the outer segment of the photoreceptor cells and, therefore, can be a useful marker for the cells. PMID- 1755336 TI - Successful use of the centrifugal ventricular assist device for postcardiotomy cardiogenic shock. AB - A centrifugal pump was successfully used as a left ventricular assist device (LVAD) in a 54-year-old female who developed cardiogenic shock following open heart surgery. Cardiac index prior to the LVAD support was 1.4 l/min/m2 and increased to 3.0 l/min/m2 at removal of the device, which assisted for 88h. She resumed her daily activity 10 months after the operation and is in New York Heart Association functional class I. PMID- 1755337 TI - The role of catalase in protecting erythrocytes against methemoglobin formation. AB - Some mechanisms to reduce methemoglobin (metHb) formation for the maintenance of normal oxygen transport have been proposed. To study the role of catalase (EC 1.11.1.6), metHb formation in the hemolysate of normal and Japanese acatalasemic human subjects were examined spectrophotometrically. Significantly increased level of metHb was induced by potassium ferrocyanide in the hemolysate of acatalasemic subject. The addition of catalase reduced the metHb formation, while 3-amino-1,2,4-triazole (AT), a specific inhibitor of catalase-H2O2 compound I, increased it. These results obtained from human subjects were well consistent with those from mice and suggested that catalase plays a role in protecting erythrocytes against metHb formation. PMID- 1755338 TI - Doppler echocardiographic evaluation of Bjork-Shiley and St. Jude Medical prostheses in the mitral position. AB - The left ventricular studies by Doppler echocardiography were performed in 50 patients with a Bjork-Shiley (B-S) mitral valve and 50 patients after implantation of a St. Jude Medical (SJM) mitral valve; the effect of valve replacement on the hemodynamic performance at rest and during bicycle exercise was determined from serial echocardiographic data. Twenty-eight patients (56%) of the B-S group and 42 patients (84%) of the SJM group showed a good response to the exercise. There was no significant difference in the effective orifice area at rest among each sizes of the B-S valve. In the SJM valve, on the contrary, the effective valve orifice area increases in parallel to the size of the SJM valve. There was a clear relation between the valve size and pressure gradient. The pressure gradient directly depends on the valve size and the effective orifice area in the SJM valve. High pressure gradient group in both prostheses had a tendency to take negative values of percent increase in stroke volume. Further, there were no cases showing positive values of percent increase in end-diastolic volume among the patients whose pressure gradients were assumed to be more than 10 mmHg at rest. It is suggested that impairment of inflow caused by the artificial valve, prosthetic valve stenosis, is possibly a significant factor causing left ventricular dysfunction, notably a decrease in stroke volume during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755339 TI - Effects of L-dopa or dopamine on human decidual prostaglandin synthesis. AB - L-Dopa and three catecholamines in the amniotic fluid before and after labor were measured to confirm the amniotic fluid catecholamine levels at the end of gestation. L-Dopa values were higher than those of three catecholamines, and dopamine which was the predominant catecholamine, rose significantly after the onset of labor. Then, to evaluate the effects of L-dopa or dopamine on prostaglandin synthesis, strips of human decidua vera obtained from fetal membranes at the time of elective cesarean sections before the onset of labor were incubated in Krebs-Ringer buffer in the presence of L-dopa or dopamine. When L-dopa was added, the net production of prostaglandin(PG)F was significantly greater than that of the control at each incubation time. On the other hand, the significant rise was observed only after 10 min of incubation for PGE2 production. Dopamine had a stimulatory effect on PGF synthesis only after 15 and 30 min of incubation, and it also stimulated the release of PGE2 at each incubation time. These results suggest that dopamine and L-dopa in amniotic fluid stimulate the production of prostaglandin by the decidua in humans. PMID- 1755340 TI - Effect of a protease inhibitor on the stability of catalase in liver and blood from acatalasemic and normal mice. AB - Effects of Gabexate mesilate (GM) (([ethyl-4-(6-guanidino hexanoyloxy) benzoate] methane sulfonate)), a protease inhibitor, on the activities of catalase in liver, erythrocytes and reticulocytes from acatalasemic mice were examined. Preincubation without GM at 37 degrees C for 160 min lowered the catalase activities of liver, erythrocytes and reticulocytes from acatalasemic mice, to 24%, 40% and 10% of the initial levels, respectively. But, preincubation with GM at 37 degrees C for 160 min delayed the rapid decrease in activities of residual catalases in the liver, erythrocytes and reticulocytes of acatalasemic mice to 65%, 93% and 85% of the initial values, respectively. At 20 degrees C or below, no reduction in catalase activity of reticulocytes from acatalasemic mice occurred with or even without GM. At pH 5.0, the decrease in catalase activity of acatalasemic mice was small both in the presence and the absence of GM. In the alkaline range, the reduction in the enzyme activity of the mutant mice without GM was enhanced with increase in pH values up to 8.5. But the presence of GM during preincubation at pH 7.5, retained the catalase activity of acatalasemic mice, to 64% of the activity at pH 6.5. These data suggest that some factors affected by GM, might be responsible for the low stability and activity of catalase in the acatalasemic mice. PMID- 1755341 TI - High tech is most effective when blended with high touch and vice versa: office technology in the 21st century. PMID- 1755342 TI - Cholesterol: truth in labeling. PMID- 1755343 TI - Chasing the medical literature. PMID- 1755344 TI - Emotional health in nursing-home patients. PMID- 1755345 TI - The family stress and support inventory (FSSI). AB - The Family Stress and Support Inventory (FSSI) is a new self-report family assessment instrument that is theoretically grounded in sociological and family stress theory and designed to provide a brief, reliable, valid, quantifiable, and global assessment of the intrafamilial stress and support variables. With reference to clearly defined constructs, the respondents rate on a continuum of 1 10 the amount of stress and support that they feel from each individual family member. Scale analysis and psychometric evaluation were completed on a randomly selected sample of 382 people chosen from family practice clinics throughout Minnesota and the University of Minnesota faculty and staff. The test-retest correlations are r = .78, p = .00 for the FSSI Support scale, and r = .68, p = .00 for the FSSI Stress scale. Correlation with social desirability is negligible (r = -.01, p = ns for FSSI Support; r = .11, p = .02 for FSSI Stress). The FSSI Stress scale demonstrates moderately high concurrent validity with the Family Inventory of Life Events and Changes (FILE), another family stress measure (r = .50, p = .00), indicating that both assess similar, but not identical, family stress dimensions. The correlation between the FSSI Support scale and the Family Inventory of Resources for Management (FIRM), another measure of family resources, however, was only r = .10, p = .05, indicating that these two measures evaluate different family support dimensions. The FSSI has many potential applications in family medicine research and clinical care where the intrafamilial stress and support variables must be quantified. PMID- 1755346 TI - Hyperemesis gravidarum: a case report suggesting new concepts and research needs. AB - Hyperemesis gravidarum has been considered an emotional disorder. Recent studies suggest that reflux esophagitis in combination with gastric dysrhythmias causes hyperemesis. A 10-week-pregnant 28-year-old woman treated successfully with antiemetics was shown to have fluctuations in gastric pH consistent with gastric dysrhythmia and reflux. Although drugs with antiemetic activity give symptomatic improvement, further research is needed to discover safe medications to treat the underlying gastric dysrhythmia. PMID- 1755347 TI - Experience with colposcopy in a family practice center. AB - The experience of a family practice center that performed colposcopy for one year was reviewed to provide insight into the appropriateness of this procedure to a family practice clinic. Almost three thousand Papanicolaou smears were performed, which prompted 97 colposcopy clinic appointments involving 68 patients. Dysplastic Pap smears accounted for 1.82% of the total. Atypical Pap smears occurred in 3.91% of the tests, and 16.1% of a sample of these demonstrated dysplasia. Controversy concerning the atypical Pap smear is discussed. The colposcopy service was convenient for the patients and was at least revenue neutral while providing a new professional opportunity for selected family practitioners. A referral base of at least 1,000 Pap smears might justify a colposcopy program, depending on referral strategies. PMID- 1755349 TI - Utilization of MEDFILE--a preprinted medical literature filing system. AB - To facilitate the creation of a personal medical literature filing system, we developed MEDFILE, a noncomputerized, preprinted medical literature filing system. A graduating medical school class that had access to MEDFILE and a control group of incoming interns were studied to ascertain satisfaction, usage, utility, and implementation of MEDFILE in comparison with traditional literature filing systems. Data were obtained from 52 recent graduates of the site school and 25 graduates of other institutions. MEDFILE users had a significantly higher satisfaction level (7.3 +/- 1.5 vs 4.5 +/- 2.7, p less than .0001, two-tailed t test), a more extensive filing system (p less than .02, chi square), and greater confidence that their filing system would remain useful during residency (p less than .0001, Fisher's exact test) than new graduates who had created their own filing systems. The data indicate that MEDFILE is an efficient, effective, and inexpensive method of organizing medical reprints. It may be particularly useful for physicians entering primary care disciplines that require information processing over a wide range of clinical topics. PMID- 1755348 TI - Do public cholesterol screenings really screen? AB - Two hospital-sponsored cholesterol-screening programs were evaluated to assess whether they detected individuals with undiagnosed high blood cholesterol. Surveys asking about prior testing, knowledge of cholesterol level, and participant characteristics were examined to test screening utilization. In both screenings 54% of participants reported having prior cholesterol testing, only 56% of whom knew their cholesterol level. Of previously untested participants, 8% had high blood cholesterol levels and 13% had borderline levels. Only 65% of participants with a personal or family history of heart attack were aware of their cholesterol level. To attract individuals without prior testing, screening planners should consider locations (eg, worksites and schools) and methods (eg, weekend screenings) to target underrepresented groups in community-wide cholesterol screenings. We encourage an increased emphasis on individualized exit education for participants, especially those who know their cholesterol level or have multiple risk factors for vascular disease. Physicians planning public screenings can utilize this data to develop parameters for referrals from the screenings. PMID- 1755350 TI - Primary family contacts and emotional health in the institutionalized elderly. AB - Research among nondemented elderly living independently in the community suggests that increased social support is associated with improved emotional and physical health. Relatively little research has examined associations between social supports and health among the institutionalized elderly. A sample of 70 nondemented, elderly nursing-home patients was studied to determine associations between qualitative and quantitative aspects of patients' relationships with their primary family contact and measures of emotional well-being, including depression, hopelessness, and life satisfaction. Significant correlations between quality of relationships and all domains of emotional well-being were found. None of the correlations between frequency of interaction and measures of emotional health were significant. A hierarchical regression analysis demonstrated that the correlation between quality of relationships and depression and life satisfaction was independent of functional status, mental status, age, type of relation, and frequency of visits. These results are consistent with studies of the noninstitutionalized elderly. PMID- 1755351 TI - Predicting the occurrence of antibiotic-induced candidal vaginitis (AICV). AB - This paper reports the sensitivity, specificity, and predictive values of symptoms in the diagnosis of antibiotic-induced candidal vaginitis (AICV) among 74 women recruited from three primary care practices. All subjects, who were examined both pre- and post-antibiotic treatment for acute respiratory, urinary tract, or skin infections, were initially free of vaginitis. Twenty-four subjects developed candidal vaginitis (CV), indicated by vaginitis symptoms or signs and a positive candidal culture or KOH preparation; there were no mixed infections. Fifty women did not develop AICV and, of this group, four developed a nonyeast vaginitis. Aggregate symptoms (pruritus and/or discharge) had 87.5% sensitivity, 95.8% specificity, and positive and negative predictive values of 91.3% and 93.9%, respectively. These values are much higher than those reported in studies of CV that excluded women on antibiotics. We conclude that women who develop vaginitis symptoms while on short courses of antibiotics may be treated as AICV without confirmatory examination. PMID- 1755352 TI - Physician impairment: physicians' exposure, attitudes, and beliefs. AB - Concern about physician impairment has resulted in increased efforts to educate physicians about its nature and scope. This study reports the results of a survey of how family physicians obtain information about impairment, which sources they value, and how exposure to impairment relates to their attitudes and beliefs. A significant association was found between involvement in group-oriented programs and recognition of risk factors unique to the profession. Important differences were found between physicians who acknowledged the role of personal vulnerability in impairment and those who attributed causality to external sources. Results also revealed that this sample of physicians was almost equally divided on whether impairment should be defined exclusively by professional conduct. PMID- 1755353 TI - Dynamic structural views of muscle contraction and its control. PMID- 1755354 TI - Changes in the X-ray diffraction pattern from rigor muscles by application of external length changes. AB - The effect of external force on the X-ray pattern from frog muscles in rigor was studied by a time-resolved diffraction technique. When sinusoidal length changes (1.5-3% of the muscle length, 5 Hz) were applied to the muscle, the 14.3 nm intensity decreased during the releasing phase and increased during the stretching phase. The intensity ratio of the equatorial 1.0 and 1.1 reflections did not change, nor were there any appreciable intensity changes in the 5.9 nm and 5.1 nm reflections during the length change. Experiments were also done with the relaxed muscles and no change was seen in any reflection, indicating that the rigor linkages are needed to produce the 14.3 nm intensity change. Thus the distinct effect of the length change was detected only on the 14.3 nm reflection. These results suggest no large conformational changes are induced in both the distal part of the myosin head attached to actin and the actin filament during the oscillation. It is therefore most probable that the proximal portion of myosin heads including S-2 contributes to the intensity change in response to the length change (see, also ref. 21). When the muscle was stretched beyond the filament overlap, the 14.3 nm intensity change was suppressed to less than 50% of that of the slack length. It was also found that the tension change delayed the intensity change during the length oscillation. However, this delay of the tension change as observed in the muscle at the slack length was lacking in the overstretched muscle, indicating that the 14.3 nm intensity change may arise partly from a portion other than the crossbridges. PMID- 1755355 TI - Mechanism of force generation studied by neutron scattering. AB - Neutron scattering has been used to compare the structure of myosin S1 that is free in solution to that when it is bound to F-actin. To achieve this, deuterated actin was obtained from D. discoideum that had been fed deuterated E. coli. This deuterated actin was rendered "invisible" to neutrons when dissolved in 94% D2O. The neutron scattering patterns obtained from S1 bound to deuterated actin were identical to those of free S1 except for oscillations due to S1's bound to the same actin filament. At low S1 to actin stoichiometries, these oscillations diminish and the patterns become indistinguishable. The apparent radius of gyration of S1 bound to actin is identical to that of free S1 when the stoichiometry is low. Thus, no changes in the structure of S1 were observed to a resolution of 2.5 nm. Computer modelling studies were used to evaluate the compatibility of models for the mechanism of force generation with the neutron data. These studies show that for powerstrokes greater than 5.0 nm, the data are consistent with more than 80% of the crossbridge maintaining a rigid conformation during force generation. PMID- 1755356 TI - Recent neutron scattering studies of muscle contraction and its control. AB - We have presented two applications of the method of neutron scattering utilizing selective deuteration of actin. In these experiments the actin was rendered effectively invisible to neutrons by matching the scattering-length densities of deuterated actin and the solvent. The scattering of neutrons by myosin S1 and by Tm bound to this actin was studied. For free chymotrypsin-generated S1 it was found that Rg = 4.0 +/- 0.15 nm, while for papain-generated S1 it was found that Rg = 4.6 +/- 0.2 nm. Upon binding of papain-generated S1 to actin at low NS1/N actin ratios, the change in Rg in difference experiments was delta Rg = 0.05 +/- 0.15 nm. This lack of significant change in Rg in the very low-s domain confirms and extends our earlier neutron scattering work in the higher-s domain. The longest chords of S1, as well as shorter ones, are not significantly altered upon actin binding. These results indicate that muscle contraction does not occur as a result of large-scale changes in S1 structure. In actin-Tm complexes, a measurement of the mean cross-helix separation, d, of Tm molecules has been made using neutron scattering. With deuterated actin matched out in 93% D2O buffer, it was found that d = 7.9 +/- 0.3 nm. This value is in good agreement with a model based on Tm crystallography and also with recent electron microscopy results. These experiments demonstrate the feasibility and value of neutron diffraction and scattering techniques in the study of muscle contraction and its control. One can expect that the further employment of emerging cell biology techniques for generating deuterated proteins will aid our understanding of muscle in the future. PMID- 1755357 TI - Two-dimensional time resolved X-ray diffraction of muscle: recent results. AB - This report provides a preliminary sketch of the results obtained in a two dimensional time resolved X-ray diffraction study of "live" frog sartorius muscles undergoing isometric tetani. These results demonstrate the recently developed capability to record time resolved (10 msec time resolution), two dimensional X-ray diffraction diagrams throughout the cycle of contraction. The correlation between the time courses of the diffraction features in the whole of the diffraction diagram establishes a sequence of structural events, which suggest that during the transition from rest to the plateau of tension and the subsequent recovery, the following sequence of events takes place: a) Following the activation phase, which is best monitored by the increase of intensity on the second actin layer line at 18.0 nm spacing (5), there is the onset of three dimensional disorder due to the filaments losing their axial alignment and the myosin heads rotating azimuthally and moving radially outwards. A set of low angle layer lines, following the actin based spacings seen in rigor (i.e., at spacings of ca. 36.5-37.5, 24.0 and 18.0 nm) become visible and those at ca. 24.0 and 18.0 nm appear to increase in intensity during this phase with a time course that cannot be determined accurately because of the proximity of the neighbouring first, second and third myosin layer lines and the weakness of these diffraction features. Whether the first of these layer lines increases or not is difficult to ascertain. Moreover, proper account of the loss in crystallinity during the development of tension must be made before the comparisons in intensity between the rest and peak of tension states have any significance. Nevertheless, these features together with the behaviour of the equatorial reflections and the meridional region of the third myosin layer line indicate that a sizeable fraction of the crossbridges may become axially disposed with an actin based periodicity. The formation of this complex does not immediately result in the generation of tension. The labelling of the thin filaments is also reflected in the main actin layer lines at 5.9 and 5.1 nm. b) The tension generating phase is monitored by the intensity changes in the meridional region of the third myosin layer line, which are best explained by a change in the orientation/conformation of the tension bearing crossbridges, (which probably adopt a more perpendicular orientation to the filament axis). c) At the end of stimulation, the crossbridges return to an axial spacing and axial orientation (although not yet azimuthal) similar to the one at rest.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1755358 TI - Structural analysis of muscle thin filament. AB - Thin sheets of Ac-Tm-Tn paracrystals were prepared in the presence of high concentration of Ca2+ ion and three-dimensional image analysis was performed. The optical diffraction pattern of an electron micrograph showed spots up to 1/1.6 nm 1 in the radial direction and up to 1/2.5 nm-1 in the axial direction, the best resolution ever obtained so far. The translationally filtered image showed clear polarity of filament which looked like a "spearhead" per each crossover repeat of actin helix. The three-dimensionally reconstructed model looked very similar to the inner regions (A+B domains) of the Ac-Tm-S1 complex obtained by Toyoshima and Wakabayashi (14, 15) when they were placed so that the "spearhead" pattern of the Tc-Tm-Tn complex and the "arrowhead" pattern of the Ac-Tm-S1 complex pointed in the same direction. The myosin-binding site of actin was identified by comparison of the two structures. The model of actin molecule cut out from the thin filament model had a low density region within itself, which was located about 2.5 nm from the helix axis. That low density region divided actin molecule into two domains, a large and a small domain. A dense "pillar" was detected which connected two neighboring actin molecules along a left-handed generic helix 1 nm from the helix axis. Two actin-actin binding sites which were responsible for the connection through the "pillar" were located on the inner surface of actin molecule. To obtain better crystalline arrays of actin, we tried a method utilizing adsorption to lipid. A positively-charged monolayer of lipids was formed on the surface of a small volume of buffer solution which was put in a microwell. Solution of negatively-charged F-actin was then injected into the buffer solution and was allowed to be joined to the lipid monolayer by electrostatic attraction. Fluidity of the lipid monolayer enabled the two-dimensional crystallization of actin. Electron microscopy revealed that larger paracrystalline arrays were formed more rapidly (less than 1 hr) than those formed within solution, which demonstrated the advantage of this adsorption method. PMID- 1755359 TI - Cryo-electron microscopy of S1-decorated actin filaments. AB - We have applied techniques for cryo-electron microscopy, combined with image processing, to both S1-decorated native thin filaments and S1-decorated actin filaments. In our reconstruction the actin subunit has a prolate ellipsoid shape and is composed of two domains. The long axis of the monomer lies roughly perpendicular to the filament axis. The myosin head (S1) approaches the actin filament tangentially, the major interaction being with the outermost domain of actin. To distinguish the position of tropomyosin unambiguously in our map, we compared the maps from decorated thin filaments with those from decorated actin filaments. Our difference map clearly shows a peak corresponding to the position of tropomyosin; tropomyosin is bound to the inner domain of actin just in front of the myosin binding site at a radius of about 40 A. As a first step toward looking at the actomyosin structure in a state other than rigor, we examined S1 crosslinked to actin filaments by the zero-length crosslinker EDC in the presence of ATP and after pPDM bridging of the reactive thiols of S1. S1 molecules of the cross-linked complexes in the presence of ATP and after pPDM treatment appear dramatically different from those in rigor. The S1s appear more disordered and no longer assume the characteristic rigor 45 degrees angle with the actin filaments. PMID- 1755360 TI - Conformations of crossbridges in contracting skeletal muscle. AB - Conformations of crossbridges during isometric contraction were observed and compared with those in rigor state. Rabbit skeletal muscle fibers were chemically skinned, rapidly frozen during isometric contraction or in the rigor state, then freeze-substituted. Longitudinal and cross sections were observed. Crossbridges in contracting fibers are arranged on the thin filament, retaining a periodicity of approximately 14.3 nm with some variability, while crossbridges in rigor fibers tend to attach to actin target zones which have a periodicity of approximately 36 nm. Rigor crossbridges are wide near the thin filament; crossbridges in contracting fibers are thinner and have more uniform width from the proximal region to the distal region. The majority of the mass of the crossbridges during contraction is not as close to the thin filament as in rigor fibers. Shapes of crossbridges during contraction are variable, especially when viewed along the filament axis. PMID- 1755361 TI - Flexibility in actin-myosin motility system revealed by in vitro motility assay. AB - Flexibility of myosin molecule was studied by in vitro motility assay in terms of the direction of actin movement. Electron microscopy showed that HMM scattered on a nitrocellulose surface can bind actin filaments and form arrowhead-like patterns. Actin filaments can move in both directions on tracks of HMM made on a nitrocellulose surface. Further, actin filaments can move bidirectionally along native thick filaments over their central bare zone. These observations indicate that there is considerable flexibility in a myosin molecule and that the direction of the movement is determined by the polarity of actin filaments. PMID- 1755362 TI - Myosin I: a new insight into the mechanism and cellular significance of actin based motility. AB - From our work on brush border myosin I structure, activity, regulation, and function, we can begin to understand the significance of the diversification of myosin proteins. While myosin I and II proteins retain conserved elements of structure that may dictate their similar mechanisms of motility and actin activated MgATPase activity, their unique structures may provide the basis for the distinct localization and regulation of the two myosin types. How does the tropomyosin-inhibited actin-binding site of myosin I differ from that of the tropomyosin-activated myosin II actin-binding site? What elements of the sites of interaction of the 110K-protein and calmodulin contribute to the conserved, light chain dependent coupling of MgATPase activity to translocation and which confer the novel calcium regulation of dissociation in vitro? It seems that the evolutionary demand for diversification of cellular motility functions has been met, at least in the actin-based system, by the evolution of isoforms tailored in structure, activity, regulation, and localization to serve complementary needs. PMID- 1755363 TI - Spontaneous oscillatory contraction (SPOC) of sarcomeres in skeletal muscle. AB - Skeletal myofibrils spontaneously oscillate under a condition where ATP, ADP, and Pi coexist and the concentration of free Ca2+ is less than about 1 microM. Although this oscillation phenomenon called SPOC is apparently simple, the molecular mechanism seems to be complex. The SPOC condition and the space-time pattern of SPOC wave suggest that the dynamics of association and dissociation of Pi (ADP) is regulated by the mechanical strain imposed on actin and myosin; the enzymatic activity (ATPase) of actomyosin complex and the mechanical event (contraction) are thus coupled to each other. In this sense, the nature of the mechanochemical enzyme, actomyosin ATPase, is revealed in SPOC. PMID- 1755364 TI - Dynamic actin interaction of crossbridges: a general principle and its implications for crossbridge action in muscle. AB - The oar-like crossbridge cycle, developed up to the mid-1970's, was shown to be inconsistent with more recent biochemical results. In crossbridge theories developed on the basis of the more recent kinetic schemes of the actomyosin ATPase in solution (Eisenberg and coworkers), however, the key elements proposed by Huxley (1957) were retained, one of which is the assumption that detachment of a force-generating crossbridge can only occur via completion of the ATPase cycle (release of ADP and rebinding of ATP). Furthermore, in these theories regulation is assumed to act by blocking/unblocking of a step subsequent to crossbridge attachment (e.g., Pi-release step). Both concepts, however, were recently shown to be in conflict with studies on skinned muscle fibers (still low ATPase activity at high-speed isotonic shortening, regulation acts via turnover kinetics and not recruitment (39]. By incorporation of the observed reversible actin interaction of crossbridges in all states, including the force-generating states, a working hypothesis can be developed (Fig. 5) which can account for the isotonic data. A mechanism by which such a scheme can also account for regulation via turnover kinetics was previously discussed (39). PMID- 1755365 TI - Dynamic X-ray diffraction of skeletal muscle contraction: structural change of actin filaments. AB - The X-ray diffraction pattern recorded during contraction shows that the force generation of a muscle proceeds upon interaction of the actin and myosin heads in the incommensurate structural framework of the thin and thick filaments. In this molecular framework the binding of myosin heads to actin filaments is thought to occur on a random basis. Such an actomyosin structure would not produce constructive interference between scattered X-rays from the bound heads and the thin filaments. The characteristic intensity changes of the thin filament layer lines that occur during contraction suggest strongly that the actin structure is varied by interaction with the myosin heads, in a manner that is quite different from that in the rigor state. Variability of the time courses of the intensity changes of the various layer lines indicates that structural change within the thin filament does not take place uniformly and that some different structural processes are involved during contraction At the plateau of isometric contraction, the thin filament structure as a whole assumes a more four-stranded nature due to the changes in the actin structure and tropomyosin position. Our present results imply that the changes of actin structure induced by interaction with myosin heads would be responsible for the regulation as well as force generation in muscle contraction. PMID- 1755366 TI - Intensification of the first actin layer-line during contraction of frog skeletal muscle. AB - The peak position of the first myosin layer-line in frog skeletal muscle shifts towards the higher angle during contraction. An analysis showed that the observed axial intensity profile of the first myosin layer-line is fitted well by summation of two layer-lines at 1/43.0 and 1/36.0 nm-1. The former corresponds to the first myosin layer-line, and the latter to the first actin layer-line whose intensity the analysis shows to increase in 0.03-0.08 nm-1 but to decrease in 0.08-0.14 nm-1 during contraction. PMID- 1755367 TI - Crossbridge states in isometrically contracting fish muscle: evidence for swinging of myosin heads on actin. AB - We have previously shown that time-resolved X-ray diffraction studies of the 2-D pattern from isometrically contracting flatfish (turbot) fin muscle have considerable advantages over similar studies of other vertebrate muscles due to the simple lattice and the better long-range order in these muscles (5, 24). Here we show not only that two structurally different myosin head to actin attached states must exist in the crossbridge cycle but that we are also able to define the likely crossbridge configurations in these states. A non-force producing "weak-binding" state is evident from the lead of the (11) equatorial reflections (and actin mass) time-course relative to that of tension (and the (10) equatorial reflection decrease) by about 30 msec. The first myosin layer line at 429 A has a weakened but altered intensity distribution, with no change in axial spacing, in patterns from active muscle. We show this to be consistent with myosin heads binding in the non-specific manner envisaged for the "weak-binding" state. Evidence for the second force-producing attached state, or series of states, comes from the observation of only a small increase in the intensity of the 360 A actin layer line between resting and active muscle patterns. It might be thought that a substantial increase in this layer line would be expected if myosin heads were even transiently attached to the thin filaments in a force-producing state. However, this is not so because internal changes in the structure of the thin filaments in active muscle have the opposite effect of causing this layer line to decrease in intensity. Observation of a small net intensity increase is therefore evidence for myosin head attachment with the symmetry of the actin helix. From the equatorial diffraction pattern, Fourier synthesis maps were computed at 10 msec intervals throughout the isometric tetanus, enabling changes in the mass distribution to be visualised between the force- and non-force producing populations of crossbridges. This difference map shows that in the force producing state myosin heads have their centres of mass on average at a smaller radius from the thin filament axis compared to the case for non-force producing myosin heads. Since there is good evidence that there is no substantial change in myosin head shape during contraction (30) these observations are consistent with myosin heads swinging on actin as fairly rigid structures. PMID- 1755368 TI - X-ray studies of thin filaments in a tonically contracting molluscan smooth muscle. AB - In the X-ray pattern of the ABRM, layer lines from the thin filaments can be clearly observed not only at the small angles but also at the medium angles up to 0.145 A-1, and the layer lines are changed in intensity in the tonically contracting state in both the small and medium angle regions. Because tropomyosin does not contribute significantly to the layer lines except the three near the equator, it is suggested that structural change of actin occurs in the tonically contracting state. The intensity profiles of the layer lines with the 0th Bessel order corresponding to the axial periods 27.9, 13.8, 9.3, and 6.9 A indicate axial staggering of the inner and outer domains of actin by about 1/3 of the axial period of actin, and the presence of a small mass on the shoulder of the outer domain at a distance of 50 A from the filament axis. The difference Patterson functions calculated from the intensities of the four layer lines with the 0th Bessel order suggest that peptide chains are oriented perpendicularly to the filament axis in the actin molecules. The peptide chain direction is presumably tilted against the filament axis in the outer part of actin as a result of structural change by tonic contraction. PMID- 1755369 TI - X-ray diffraction studies on muscle regulation. AB - Using the intensity of the outer part of the second actin layer line as an indicator of thin filament conformation in vertebrate muscle we were able to identify the four different states of rest, and the three states induced by the presence of Ca2+ ions, rigor bridge attachment and actively cycling bridges, respectively. These findings are in qualitative agreement with a number of biochemical studies by Eisenberg and Greene and others, indicating that activation of the thin filament depends both on Ca2+ ions and crossbridge binding. Yet quantitatively, the biochemical data and our structural data are contradictory. Whereas the biochemical studies suggest a strong coupling between structural changes of the thin filament and the ATPase activity, the structural studies indicate that this is not necessarily the case. Troponin molecules also change their conformation upon activation depending on both Ca2+ ions and crossbridge binding as demonstrated by the early part of the time course of the thin filament meridional reflections in contracting frog muscle. Low ionic strength which has been shown by Brenner and collaborators to increase weakly binding crossbridges in relaxed rabbit psoas muscle does not influence the intensity of the second actin layer line in this muscle. Yet in contracting frog muscle the increase of the second actin layer line increases very rapidly in one step, suggesting that weak binding bridges which are attached to actin prior to force production may indeed influence the thin filament conformation. It therefore appears that weakly bound bridges in the low ionic strength state do not have the same effect on the thin filament conformation as weakly bound bridges in an actively contracting muscle. Arthropod muscles like the thin filament regulated lobster muscles differ from vertebrate muscle in not showing an increase of the second layer line during contraction, which may have to do with differences in crossbridge attachment. The myosin-regulated molluscan muscle ABRM shows a large increase on the second actin layer line upon phasic contraction and a much smaller increase in catch or rigor, indicating that actively cycling bridges influence the thin filament conformation differently than catch or rigor bridges. Several pieces of evidence which we have briefly outlined in this paper suggest that the thin filament conformational changes we have observed do not arise solely from tropomyosin movements and that conformational changes of actin domains should be considered. PMID- 1755370 TI - Granulocyte and monocyte chemotactic factors: stimuli and producer cells. PMID- 1755371 TI - Chemotactic cytokines in inflammatory skin disease. PMID- 1755372 TI - Activation of human neutrophils by NAP-1 and other chemotactic agonists. PMID- 1755373 TI - Interleukin-8--a mediator of inflammatory lung disease? PMID- 1755374 TI - Some aspects of NAP-1 pathophysiology: lung damage caused by a blood-borne cytokine. PMID- 1755375 TI - NAP-1/IL-8 in rheumatoid arthritis. PMID- 1755376 TI - Induction and regulation of interleukin-8 gene expression. AB - Recent advances in understanding granulocyte elicitation have been made with the discovery and isolation of chemotactic cytokines. There is little doubt that these polypeptides will prove to be important mediators of disease process. Therefore, studies directed at understanding the production and regulation of interleukin-8 will continue to be a fertile area to explore mechanisms of disease processes and therapeutic targets. PMID- 1755377 TI - Regulation of human interleukin 8 gene expression and binding of several other members of the intercrine family to receptors for interleukin-8. AB - IL-8 is produced by a wide variety of cells in response to polyclonal mitogens and cytokines. Northern blotting analysis revealed that IL-1, TNF and PMA could induce rapid expression of IL-8 mRNA in the absence of new protein synthesis. Nuclear run-off assays using different cell types demonstrated that IL-8 mRNA expression could at least be partly due to the activation of transcription. Cloning and determination of the entire sequence of IL-8 genomic DNA enabled us to explore the functional significance of the 5'-flanking enhancer region of the IL-8 gene by employing CAT assays. The results indicated that the region spanning from -94 to -71 bp is minimally sufficient for conferring responsiveness to IL-1, TNF and PMA. Further analysis using point-mutations revealed that this region consisted of two distinct cis-elements; one being the potential binding site for NFkB-like and the other for a C/EBP-like factor. These results suggested that all three stimuli, IL-1/TNF/PMA, modulate the identical combination of nuclear factors possibly by phosphorylation. We previously reported that these three stimuli activated the same serine protein kinase which phosphorylates identical 65 kDa and 74 kDa cytosol proteins in human PBMC. This IL-1/TNF/PMA-activated protein kinase is distinct from protein kinase A, protein kinase C or casein kinase in substrate specificity; in Ca and phospholipid dependency; in cyclic nucleotide dependency; and sensitivity to protein kinase inhibitors. Taken collectively, IL-1/TNF/PMA may activate a common serine protein kinase and this protein kinase may in turn directly or indirectly modulate several nuclear factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755378 TI - Formation and biological properties of neutrophil activating peptide 2 (NAP-2). PMID- 1755379 TI - Biological aspects of monocyte chemoattractant protein-1 (MCP-1). AB - In this communication, we have asked if MCP-1 is the mediator of cellular infiltration in DCH, outlining the criteria in Table 3. Preliminary data suggest that PHA-stimulated lymphocytes secrete MCP-1, and that MCP-1 can be produced in response to antigen stimulation. MCP-1 attracts monocytes and basophils, but not neutrophils. The question of a lymphocyte response to MCP-1 requires further study. We have emphasized that the discovery of leukocyte-specific NAP-1 and MCP 1 should now be followed by exploration of conditions in which one agonist is secreted without the other. This would be expected, for example, in DCH, which is characterized by mononuclear leukocyte infiltration without neutrophils. PMID- 1755380 TI - Stimulus specific induction of monocyte chemotactic protein-1 (MCP-1) gene expression. AB - The recruitment of monocytes from the peripheral vasculature to an area of chronic inflammation is a complex phenomenon. This complicated process is likely mediated to a large extent by chemotactic cytokines that are expressed via a cytokine cascade. A number of chronic diseases that are difficult to manage are characterized by a significant infiltrate of monocytes, including sarcoidosis, Wegener's granulomatosis, and tuberculosis. New scientific insight into the mechanisms that lead to early activation events, such as monocyte elicitation, may aid in both better understanding these diverse processes and designing more effective therapies. PMID- 1755382 TI - PDGF and the small inducible gene (SIG) family: roles in the inflammatory response. AB - A growing body of evidence suggests that cells responding to an initial growth, inflammatory or immune signal can respond by inducing the transcription of selective members of the SIG family. This family of related inducible cytokines are involved in the amplification, propagation and coordination of intercellular communication among cell types involved in the immune and inflammatory responses. The principal anti-inflammatory action of glucocorticoids may involve the transcriptional and translational inhibition of cytokines such as JE and other members of the SIG family to effectively disrupt the normal lines of intercellular communication which normally coordinates the immune and inflammatory response. The identification of new members of the family and the discovery of the functions of the known members will lead to a clearer understanding of the complicated processes which lead to normal and pathological immune and inflammatory responses. PMID- 1755381 TI - GRO: a novel chemotactic cytokine. PMID- 1755383 TI - Human neutrophil granule cationic protein CAP37 is a specific macrophage chemotaxin that shares homology with inflammatory proteinases. AB - Cationic antimicrobial protein CAP37 (Mr = 37 kD) is derived from the azurophilic granules of human PMN. In vitro and in vivo studies demonstrate that CAP37 is a novel monocyte-specific chemoattractant. The N-terminal amino acid sequence of CAP37 shares significant homology with a number of inflammatory molecules with protease activity including elastase and cathepsin G. However, substitutions in the catalytic triad (serine for a histidine at position 41 and glycine for a serine at position 175), may account for its lack of serine protease activity. A full length cDNA for CAP37 was identified in an HL60 cDNA library screened with oligonucleotide probes designed from the N-terminal amino acid sequence. Sequencing of the cDNA reveals a protein of 225 amino acids with significant nucleotide homology to cathepsin G and human neutrophil elastase. PMID- 1755384 TI - Biochemical and biological characterization of NAP-1/IL-8-related cytokines in lesional psoriatic scale. PMID- 1755385 TI - National Health Service nursing homes again. PMID- 1755386 TI - A randomized controlled trial of nursing home and long-stay geriatric ward care for elderly people. AB - This paper reports outcome data on mental and physical ability levels, mortality and accident rates, from a randomized controlled trial evaluating health authority funded nursing home and long-stay geriatric ward care in one inner London health district. There were no differences between settings in mortality rates, although respondents randomized to the nursing homes deteriorated more rapidly in overall, mental and functional ability levels. Previous analyses reported that they also experienced a higher accident rate than respondents in the wards. However, observational data from the evaluation clearly indicated that quality of life in the homes was superior to that in the wards. We conclude that the more rapid physical decline and greater risk of accident in the nursing homes have to be balanced against an inferior quality of life in the hospital, and that a judgement is not easy to make on behalf of other people. PMID- 1755387 TI - Respiratory symptoms among elderly people in the New Forest area as assessed by postal questionnaire. AB - This study was carried out to estimate the prevalence of respiratory symptoms among people aged 65 years and older and assess the value of a postal survey in obtaining this information. A questionnaire was sent to 2011 subjects (957 men) drawn by age-stratified random sampling from the age-sex registers of four New Forest group practices (1:3.3 sample). A total of 1803 replied, a 96.2% response after excluding 136 who had died or moved from the area. The accuracy of replies was verified for 355 (20%) randomly selected subjects. Forty per cent had no respiratory symptoms. Exertional breathlessness was common (38%), increasing in prevalence with age but not with smoking history, and was the only symptom reported by 10% of subjects. Only 14.2% were current smokers; more of the subjects aged 85 years and over were lifelong non-smokers. Two hundred and ninety six (16.4%) had chronic bronchitis, which was more common among smokers; 151 (8.4%) gave a history of asthma, of whom half (76) had active asthma, which was slightly less common among the very elderly subjects. Only 489 (27.1%) of subjects had seen their doctors with chest symptoms during the preceding 2 years. PMID- 1755388 TI - The abbreviated mental test: its use and validity. AB - The validity of the Abbreviated Mental Test was demonstrated by comparison with final clinical diagnoses in a consecutive sample of 168 patients admitted with acute illness to a department of health care of the elderly. Fifty-eight (34%) had abnormal cognition. The best cut-off point was 8, with less than 8 suggesting abnormal cognitive function. A short version (the AMT7) of the AMT was developed. Its validity, internal consistency and coverage of domains was equivalent to the AMT but it had a slightly higher sensitivity (with acceptable specificity) than the original. This new short version may improve performance of junior doctors in clinical practice who appear to have difficulty remembering all 10 items of the AMT. PMID- 1755389 TI - Long-term outcome for patients and carers following hospital admission for stroke. AB - Outcome was assessed in 82 3(+)-year survivors from a cohort of 229 patients admitted to hospital with acute stroke; 71% were independent or only mildly disabled, 76% were living at home. Institutionalized patients were significantly older, less often married, and had more cognitive impairment than those at home. No patient who produced normal picture drawings (house, man, clock) was in institutional care, only two patients living alone had abnormal drawings. Of patients at home 39% had not seen their general practitioner (GP) in the last 6 months. GPs were less likely to see patients who were more severely disabled (p less than 0.05). Targeting of services seemed poor, there was no relationship between level of dependence and level of support from voluntary or statutory services. Forty-four of 49 chief informal carers were also interviewed; 30% showed marked strain. Carers had more problems with emotional reactions, sleep and social isolation than expected. PMID- 1755390 TI - Evidence of cellular zinc depletion in hospitalized but not in healthy elderly subjects. AB - Cellular immune function declines with age and is implicated in the increased incidence of cancer, and morbidity and mortality associated with infections in elderly people. Elderly people are at risk of nutritional depletion, including of zinc, and zinc is known to influence immunity. The present study assessed zinc status in both healthy elderly subjects and elderly inpatients. Polymorphonuclear cell zinc was decreased in the hospitalized subjects and 27% had values below the reference range for healthy elderly and young subjects. Since PMNC zinc is decreased in experimental zinc depletion and correlates with muscle zinc, we suggest that 27% of the patients studied may be zinc depleted and may benefit from zinc supplementation. PMID- 1755391 TI - Glycated proteins in elderly type II diabetic patients: role of age and serum protein concentration. AB - In an attempt to evaluate the clinical significance of fructosamine (F) and glycated haemoglobin (HbA1c) values in elderly diabetic patients, 49 patients with mean age 72.0 years and 58 patients with mean age 51.6 years (control group) were studied. No difference was found in F and HbA1c between the two groups, when the degree and duration of glycaemic failure was equal. However, on extrapolating from the two groups those patients with total protein less than or equal to 6.0 g/dl, it was observed that these subjects had F values significantly lower than the other patients studied (p less than 0.001) although there was no difference in the degree and duration of metabolic failure. It was concluded that F and HbA1c can also be used in elderly patients providing they are normoproteinaemic. In the case of hypoproteinaemics, the F values are underestimated and do not correlate with the other indices of glycaemic control. PMID- 1755392 TI - A population survey of cardiovascular disease in elderly people: design, methods and prevalence results. AB - A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755393 TI - Symptoms of gastro-oesophageal reflux disease in elderly people. AB - The frequency and the possible age-related characteristics of gastro-oesophageal reflux disease (GORD) were investigated in 195 consecutive elderly subjects (mean age 74 years), referred to endoscopy for abdominal symptoms or sideropenic anaemia. In the 105 of these patients in whom there was any suspicion of GORD, 24 hour pH monitoring was carried out. All the patients were interviewed before the examinations. Erosive or complicated (grade 2-4) oesophagitis was found in 18% of patients. The main symptoms in these patients were dysphagia, respiratory symptoms and vomiting. Chronic cough, hoarseness or wheezing were present in 57% of patients with oesophagitis compared with 33% of those without oesophagitis (p less than 0.001). The occurrence of heartburn and regurgitation did not differ significantly between patients with or without oesophagitis, although the mean symptom scores were higher in those with oesophagitis. Dyspepsia and chest pain were not typical symptoms in oesophagitis. Of patients with oesophagitis 29% had no typical symptoms of GORD; only 24% of patients with regurgitation had oesophagitis. In 24-hour pH monitoring, a significant increase in the occurrence of symptoms was not seen until total reflux time pH less than 4 exceeded 10%. The occurrence of heartburn did not correlate with the extent of reflux in the pH study. In conclusion, typical symptoms of GORD in the aged were regurgitation, dysphagia, respiratory symptoms and vomiting rather than heartburn. PMID- 1755394 TI - Peptic ulcer disease in older age groups in Gothenburg in 1985: the association with smoking. AB - The prevalences of peptic ulcer and smoking were assessed by a questionnaire sent to 6726 residents of Gothenburg selected at random from the birth cohorts 1945, 35, -25, -15, and -05. The point prevalence of peptic ulcer was in all age groups significantly higher among smokers than among non-smokers. The incidence of peptic ulcer in 1985 was deduced from records of ulcers detected at gastroscopy and/or radiography and/or emergency surgery (n = 1402). Smoking habits and previous episodes of peptic ulcer disease were evaluated. The estimated risk of getting peptic ulcer was significantly higher among smokers in all age groups and of both sexes than among non-smokers. Among non-smokers the risk of getting peptic ulcer was significantly higher in men than in women, whereas the risk among smokers showed no sex difference. In people aged 35-84 years, 25.4% (n = 101) of ulcers diagnosed for the first time and 42.0% (n = 246) of relapsing ulcers were estimated to be caused by smoking. The number of smoking years, however, could not be shown to influence the risk of peptic ulcer. PMID- 1755395 TI - Age is no bar to sexually acquired infection. AB - Two hundred and forty-two patients aged 60 years or over attended genito-urinary clinics in Nottingham and Leicester (England) in a 2-year period. Sixty-nine per cent of men and 53% of women were sexually active and 58 were found to have sexually transmitted diseases. PMID- 1755396 TI - Effectiveness of inhaled bronchodilator delivery systems for elderly patients. AB - A prospective study of inhaler technique using aerosol metered dose inhalers (MDIs), Rotahalers and a breath-activated device (Aerolin Autohaler) was undertaken to assess how effectively elderly patients use their inhalers. Fifty one patients aged 67-89 years (mean 77.4 years) were enrolled. Peak flow, FEV1 and FVC were recorded, before and after inhalation of 2.5 mg of salbutamol via a nebulizer, to assess the extent of reversible airways obstruction. Inhaler technique was assessed using a scoring system, based on performance in five aspects of inhaler use. Those with poor technique were randomly allocated to an alternative inhaler and reassessed. Twenty-nine of 51 patients demonstrated reversibility in their airways disease. Twenty-one of 47 had poor technique using an MDI and were given Rotahaler or Aerolin devices to use. Ten of 11 given Aerolin Autohalers improved but seven of ten using Rotahaler showed no improvement (p = 0.006). Subsequently, five of these seven were able to improve their technique with the breath-activated autohaler. The breath-activated Aerolin Autohaler is a better delivery system than Rotahalers for inhaled bronchodilators for elderly patients. PMID- 1755397 TI - [The effect of kanpou medicine on the growth and aggregation of calcium oxalate crystals in vitro]. AB - The effects of the compositional drugs of kanpou medicine on the growth and aggregation of calcium oxalate crystals were investigated in vitro. In the seeded crystal system, the inhibitory activities were calculated from the change of the number (Ia), total volume (Ig) and fractional volume (I) of crystals determined by a Coulter Multisizer. Among the tested drugs (Takusha, Akyou, Chorei, Bukuryou, Kasseki, Kinsensou, Kagosou), only Takusha and Kagosou had strong inhibitory activities on the growth and aggregation at the concentration of 5 micrograms/ml and 10 micrograms/ml (Ia greater than 80%, Ig, I greater than 90%). No significant correlation was observed between inhibitory activities and alcian blue precipitable polyanions (ABPP) of each drug. Thus some naturally existing substances composing the kanpou medicine may help prevent the stone formation in clinical use. PMID- 1755398 TI - [Citrate as an inhibitor of stone formation--with reference to intestinal citrate absorption and the influence of citrate on intestinal calcium absorption]. AB - The response of serum citrate to the oral citrate load was studied in seven healthy subjects. Serum citrate was significantly elevated from 15 to 60 min post load with some individual variations. In 27 stone-formers serum citrate and the response to the oral citrate administration was studied and compared with the results obtained on healthy subjects. The serum citrate concentration of stone formers was 1.99 +/- 0.49 mg/dl as compared to 1.61 +/- 0.35 mg/dl in healthy subjects. After citrate administration serum citrate increased significantly in both groups, but no significant difference was shown in response to the oral citrate load between these two groups (3.44 +/- 0.94 mg/dl in stone-formers, 3.16 +/- 0.38 mg/dl in healthy subjects). In Sprague-Dawley rats each weighing about 200 g urinary citrate and calcium excretion were studied after administration of sodium citrate or calcium chloride or both. The concomitant equimolar administration of sodium citrate and calcium chloride did not have significant influence on urinary citrate or calcium excretion as compared when citrate or calcium was given alone. However, the calcium excretion was significantly decreased with the administration of citrate and calcium ata molar ratio of 1:2. PMID- 1755399 TI - [Combined administration of calcium and citrate reduces urinary oxalate excretion]. AB - Three grams of calcium lactate and 3 g of uralyt U were administered to 39 calcium oxalate stone formers. Urinary oxalate level was reduced significantly without raising urinary calcium level by the administration of the two drugs for two weeks. The mechanism of action of these drugs and the diet which might produce a similar effect were discussed. PMID- 1755400 TI - [Oxalate as a promoter in calcium oxalate nephrolithiasis]. AB - Oxalate transports on membranes of red blood cell, intestinal epithelium and proximal tubule cell were reviewed, and the new findings about oxalate transport across these membranes are reported. Red blood cell oxalate influx rate in a group of recurrent calcium oxalate stone formers was significantly higher than that of a control group. In the red blood cells of mammals, the band 3 protein transports oxalate. Although abnormal influx rate of red blood cells might be recognized as an expression of somatic cell abnormality of oxalate transport in some recurrent stone formers, the band 3 protein is not related to oxalate transport in both kidney and intestine. The study using brush border membrane vesicles suggested the presence of Na-oxalate co-transport. In humans, sodium intake increased the oxalate/creatinine ratio of urine. This indicated that excessive sodium intake might be a risk factor of stone formation. Further study of oxalate transport of both kidney and intestine will be required to elucidate an etiology of calcium oxalate nephrolithiasis. PMID- 1755401 TI - [The pitfall of ESWL]. AB - The pitfall of extracorporeal shock-wave lithotripsy (ESWL), such as complications of ESWL, problems of focus and results of stone disintegration are discussed. The progress of ESWL today is mainly due to the development of new generation lithotripters and endourological support, which has broadened the indications of ESWL. The necessary shock-waves have been selected, and complications have been reduced. Post ESWL stone street is now easier to treat. We expect more improved lithotripters such as by incorporation of X-ray and echo focusing systems. Endourological techniques including laser lithotripsy also should be improved. PMID- 1755402 TI - [Extracorporeal shock wave lithotripsy for ureteral stones and cystine stones]. AB - We report our experience with extracorporeal shock wave lithotripsy (ESWL) in the treatment of ureteral and cystine stones, which are known to be difficult to treat by this method. First, in order to determine the effectiveness of the ureteral catheter in the destruction of ureteral stones, we compared the clinical results of 121 patients treated without the catheter and 141 patients inserted with the catheter. There was no significant difference in the success rate between the two groups regardless of stone size, which indicates that the use of the ureteral catheter had no effect on the outcome of treatment. We then studied the clinical results of impacted ureteral stones which are especially difficult to destroy. Excretory urography was performed to non-invasively diagnose these stones, and those without visualization in the ureter below the stone were diagnosed as impacted stones and treated by ESWL without the ureteral catheter. Among the stones with a diameter of 1 to 2 cm, the success rate was significantly lower in impacted stones compared to non-impacted stone. These findings suggest that ESWL treatment without the ureteral catheter may be effective for ureteral stones with a diameter of less than 1 cm and non-impacted stones with a diameter of 1 to 2 cm, while combination therapy with other methods such as TUL may be better for other stones. We also performed ESWL on 6 patients with renal stones and 2 patients with ureteral stones which were cystine stones. Renal stones required an average 4.1 treatment with an average of 1,875 shocks per treatment, and ureteral stones required 1.5 treatment with an average of 1,833 shocks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755403 TI - [The effectiveness of prophylactic dietary treatment in renal stones]. AB - By following individual dietary guidelines which were established from analysis of the dietary intake and habits of male renal stone patients, the stone recurrence rate in 75 male calcium stone patients who had only received individual dietary instruction decreased markedly, as compared with that in 114 male calcium stone patients who had not received such instructions. Among 75 patients, recurrence was noted in 6 normocalciuric recurrent stone patients and 1 normocalciuric single stone patient during the period of outpatient visits. Investigation of the daily consumption of various nutrients and urinary excretion revealed no differences among the 6 normocalciuric recurrent stone patients, hypercalciuric recurrent stone patients, hypercalciuric single stone patients and normocalciuric single stone patients. Our findings suggest that the high recurrence rate in the normocalciuric recurrent stone patients is associated with stone lithogenic factors, such as heredity and anatomy, that could not be controlled by the daily treatment in this group. PMID- 1755404 TI - [Diagnosis of the acute rejection]. AB - A questionnaire survey, concerning the immunosuppressive treatment and criteria of diagnosis in acute rejection of renal allografts, was done at 22 institutes. In 15 institutes, 3 immunosuppressive agents were used. Those agents were as follows: prednisolone (Pr.) or methyl-prednisolone (M-Pr.), cyclosporin (CsA) and azathioprine (Az.) or mizoribine (Mz.) or anti-lymphocyte globulin (ALG). A combination of 4 drugs (Pr. or M-Pr. +CsA +Az. or Mz. +ALG) was used at 4 institutes and a combination of 2 drugs (Pr. or M-Pr. +CsA) at the remaining 3 institutes. Acute rejection episodes were diagnosed by conventional criteria in all institutes. Conventional criteria were as follows: physical findings, rising serum creatinine, response to pulse therapy, rising urinary FDP, decreasing urinary Na/K ratio and radionuclide findings. In our cases, there was no significant difference between the number of acute rejection episodes by the 25 patients who underwent conventional immunosuppressive therapy (C group:M-Pr.+Az.) and the 25 patients with triple immunosuppressive therapy (T group: M-Pr. +CsA+Az.). Conventional methods were sufficient in most cases of the T as well as C group to diagnose acute rejection episodes. PMID- 1755405 TI - [Effects of verapamil on cyclosporine. A (CsA)-induced nephropathy in ischemic kidney model in rats: changes in systemic hemodynamics and hepatic and renal microsomal cytochrome P-450]. AB - We have examined the effect of verapamil on CsA-induced nephropathy by measurement of systemic hemodynamics including each organ blood flow using the microsphere method in ischemic kidney model of hemi-nephrectomized Wistar rats. Hepatic and renal microsomal cytochrome P-450 contents and their enzyme activities were measured to study the correlation between CsA-induced nephropathy and induction of hepatic and renal microsomal cytochrome P-450. All rats were hemi-nephrectomized (l-nephrectomy) and were classified into the following 6 groups: 1) control groups, 2) CsA at a dose of 40 mg/kg per day orally for 7 days (CsA group), 3) Oral administration of verapamil for 7 days in the CsA group (CsA + V group), 4) 20 min clamping of the remaining right kidney pedicle (Ischemic, Is group), 5) CsA was administered in the Is group (Is + CsA group), 6) Addition of verapamil to CsA in the Is + CsA group (Is + CsA + V group). Verapamil was given in the drinking water and the average dose calculated from the amount of drinking was 4.7 +/- 1.0 mg/kg per day and 5.2 +/- 0.7 mg/kg per day for the CsA + V group and the Is + CsA + V group, respectively. CsA caused significant increases in BUN and serum creatinine (sCr) with a significant decreases in renal inulin clearance (CIn) in all groups. When compared with the Is group, CsA caused significant decreases in cardiac output and all organ blood flow especially in renal blood flow with significant increases in BUN and sCr in the Is + CsA group.2+ degree of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755406 TI - [Cyclosporine induced nephrotoxicity and renal blood flow]. AB - To elucidate the relationship between cyclosporine (Cs) nephrotoxicity and renal blood flow (RBF), we carried our experiments using rats. Adult male Wistar strain rats each weighing about 100 g were used. Rats were divided into 2 groups; the Cs group (Cs 50 mg/kg/day was intraperitoneally given for 10 consecutive days) and the control group (normal saline solution for 10 consecutive days). The renal cortical blood flow was measured in each group by electrolytic hydrogen gas clearance method. We also carried out renal angiography with barium sulfate (BaSO4). Then we measured blood vessel area/renal sagittal section area ratio and the diameter of interlobar arteries. The Cs group showed a significant decrease of renal cortical blood flow compared with the control group. On the other hand there was no significant change in renal angiogram. In conclusion, Cs decreased renal cortical blood flow. We suppose that vascular resistance increased following afferent arteriolopathy caused by Cs administration. PMID- 1755407 TI - [Distribution of ciclosporin in the lymphoid tissue]. AB - To clarify the distribution and the kinetics of ciclosporin (CSA) in the lymphatic system, we measured the CSA level of the lymph from the thoracic duct drainage (TDD) and that of the peripheral blood after oral or intravenous administration of CSA in 13 TDD pretreated patients. We also measured the CSA level of the iliac lymph nodes in 20 patients undergoing transplant surgery. The mean CSA level of the lymph was 1,647 ng/ml in the first 2 hours, 1,551 mg/dl in the next 10 hours and 254 ng/dl in the last 12 hours in orally administered patients and the mean CSA level of the peripheral blood was 746 ng/ml at 2 hours, 263 ng/ml at 12 hours and 119 ng/ml at 24 hours later. In intravenous administration, the mean CSA level of the lymph was 68 ng/ml, 58 ng/ml and 33 ng/ml and the mean CSA level of the peripheral blood was 452 ng/ml, 105 ng/ml and 88 ng/ml respectively. The mean CSA level of the lymph node was 3,222 ng/g and the mean diffusion rate from the peripheral blood to the lymph node was 17.1. There was no difference between oral and intravenous administration. These results indicated that (1) there is a second pathway in which orally administered CSA is transported from small bowel to general circulation; via mesenteric lymph duct, thoracic duct and subclavic vein and (2) CSA is selectively uptaken by lymph node. CSA might suppress the activation of T cells in the lymph node and the lymph more effectively than in the peripheral blood. PMID- 1755408 TI - [Urinary tract infections after kidney transplantation]. AB - Clinical significance of urinary tract infections (UTI) after kidney transplantation was studied in 57 cases. Of these patients, the UTI occurred in 63% of cases during follow-up after transplantation. Although the bacteriuria were observed more frequently in living-related donor (LD) group at pre operation, cadaveric donor (CD) group showed significantly higher frequency in bacteriuria and UTI after transplantation. The initial UTI occurred within 4 weeks after transplantation in 86% of cases. The significant risk factors in the occurrence of UTI were presence of bacteriuria in post-operation, CD group, mismatch numbers in HLA, amount of steroid, and ages of donor and recipient. Of the bacteria isolated, about half were pathogens in UTI, which was a 2 times higher risk compared with the time of chronic hemodialysis. Gram negative rods were found to be major pathogen in UTI cases. The effect of UTI on graft survival was not obvious. However, of the patients who have bacteriuria at operation, 52% were found to have bacteriuria due to the same strain during follow-up. Therefore, bacteriological examination of urine at transplantation must be done carefully. PMID- 1755409 TI - [Primary hyperparathyroidism: problems on surgical indication and procedure]. AB - Between 1959 and Oct. 1990, 307 cases of primary hyperparathyroidism (PHPT) were operated on in our hospital. Among them, 23 cases (7.5%) were asymptomatic chemical type of PHPT, and the incidence of this type has been increasing these days. Various symptoms or signs including urolithiasis, bone disease, cardiovascular disease, gastrointestinal disease, diabetes mellitus and others were associated with PHPT. Especially, as a lethal factor, malignant tumors developed in 14 cases (4.6%); 9 cases of non-medullary thyroid cancer and tumors of other organs. In consideration of these associated disorders, the chemical type of PHPT should be operated prophylactically. In order to reduce operative complications, unilateral exploration is available for the cases of single normally localized adenoma; 85.7% of our 307 cases. Moreover, the positive rate of preoperative localized test by CT and ultrasonography for such adenomas is 78% in the recent 5 years. The predictive values of successful operation by unilateral exploration are 89% in the cases of normally localized single adenoma and 76% in all PHPT. PMID- 1755410 TI - [A clinical study on primary hyperparathyroidism--indication of operation and surgical technique]. AB - Fifty-two cases of primary hyperparathyroidism were experienced at Kyoto University Hospital and affiliated hospitals between 1965 and 1990. Thirty-three of them (63%) were of the stone type, twelve (23%) of the bone or mixed type, seven (13%) of the chemical type. Histopathological findings showed adenoma in 49 cases and hyperplasia in 3 cases. Serum calcium levels decreased postoperatively in all cases of adenoma but unchanged in 2 of 3 cases of hyperplasia. For parathyroid adenoma, the accuracy of localization was more than 90% by the combination of computed tomography, magnetic resonance imaging, ultrasonography, subtraction scintigraphy with 201TI and 123I, venous sampling for parathyroid hormone and/or angiography. Simple removal of parathyroid adenoma may be recommended in a case of primary hyperparathyroidism due to a single adenoma which was revealed by preoperative image diagnosis. PMID- 1755411 TI - [Indications for surgical treatment of secondary hyperparathyroidism]. AB - From 1978 to 1990 subtotal parathyroidectomy was carried out on 41 patients for secondary hyperparathyroidism. The indications for parathyroidectomy and suitable operative time, especially in the point of view of renal osteodystrophy are discussed. Serum ALP and PTH level and the presence of generalized fibrous osteitis were good indicators for parathyroidectomy. Furthermore, 99mTc Pyrophosphate bone scintigraphy and Dual Photon Absorptiometry were proved to be valuable for patient selection for parathyroidectomy. Parathyroidectomy for patients in whom 99mTc-pyrophosphate bone uptake is diminished or patients in whom bone mineral contents are dramatically decreased must be carefully performed. PMID- 1755412 TI - [The effect of conservative and surgical management for secondary hyperparathyroidism and their problems]. AB - We compared the effect of conservative treatment with that of surgical treatment after applying them on secondary hyperparathyroidism patients (2nd HPT) in order to study the application of surgery on 2nd HPT patients. We selected the test subject of 39 maintenance dialysis patients with complications of 2nd HPT. The conservative treatments were; elcitonine administration (40 u x 3/W) (group 1), ipriflavon administration (200 mg x 3/day) (group 2), and pulse treatment (1.25 (OH)2D3 6 micrograms/W) (group 3). For surgical treatment, we adopted total parathyroidectomy with auto-transplantation into the arm (PTX). The transition of serum parathyroid hormone (PTH-C), alkali-phosphatase (ALP), bone scintigraphy of every 6 months, and change of bone mineral content (BMC) were compared to judge the effects of treatments. We measured 1/3, 1/6 radial region with single photon absorptiometry (SPA) and L3 region with dual photon absorptiometry (DPA) to obtain BMC. We were forced to transfer the patients in groups 1 and 2 (conservative treatment) to pulse treatment or PTX as 12 months later they showed increase in serum PTH-C, ALP and significant drop (P less than 0.05) in BMC average change rate (1/3). In group 3 of pulse treatment, though significant decrease in serum ALP (P less than 0.01) was detected for 10 cases out of 12, serum PTH-C was either unchanged or increased for 4 cases with the value of more than 30 ng/ml. Furthermore the average change rate of BMC stayed at the same level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755413 TI - [Technique and problems of total parathyroidectomy with autotransplantation in secondary hyperparathyroidism]. AB - Between 1982 and 1990, 20 patients with chronic renal failure underwent total para-thyroidectomies and autotransplantations as treatment for secondary hyperparathyroidism. Fourteen cases were cured of their symptoms and their serum PTH levels was restored to normal. Recurrent hyperparathyroidism developed in 6 cases. In 3 of the 6 cases, excision of parathyroid tissue from the forearm could easily be performed under local anesthesia. Of the other cases, 2 had five and one had six glands. Several localizing methods should be performed before operation, in order to overlook the parathyroid glands in different anatomic positions. PMID- 1755415 TI - [Clinical and pathological studies on incidental renal cell carcinoma]. AB - During the five-year period from 1985 to 1989, a total of 69 patients with renal cell carcinoma received treatment at Daisan Hospital of Jikei University School of Medicine. Among these patients, there were 23 patients (33.3%) with incidental renal cell carcinoma. These 23 cases were studied clinically and pathologically in comparison with 46 symptomatic cases. The tumor was detected by ultrasonography (US) or computed tomography (CT) conducted for the diagnosis of other diseases in 16 cases and by US included in the battery of physical examinations in the remaining 7 cases. As compared to symptomatic cases, less hematological abnormalities were found in these cases, since ESR was accelerated in only 2 cases and anemia and elevation in alpha 2-globulin level were found in none of the cases. As for diagnostic imaging, CT could detect the tumor in all of 23 cases and US in 20 out of 21 cases. Intravenous pyelography gave normal pyelograms in 4 cases. Normovascular findings were obtained by renal angiography in 2 cases. The mean largest diameter of tumors of these 23 cases was 3.9 cm, being smaller than the corresponding mean diameter of 7.7 cm for symptomatic cases. In 8 out of 23 cases tumors were small renal cell carcinoma of 2.5 cm or less in diameter. Pathologically, incidental renal cell carcinoma was characterized by small size, expansive growth pattern (INF alpha in 18 cases and INF beta in 5 cases) and prevalence of clear cell subtype (clear cell subtype in 18 cases, granular cell subtype in 2 cases and mixed cell subtype in 3 cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755414 TI - [A clinical study on renal cell carcinoma]. AB - A retrospective study was carried out on 95 patients affected with renal cell carcinoma (RCC) between January 1973 and December 1988. Male to female ratio was 3 to 1 and the average age was 61 years. Hematuria was the most common initial symptom (44 patients, 46.3%), followed by incidental findings (18 patients, 18.9%). Five- and 10-year survival rates for all patients with RCC were 51.9 and 37.1%, respectively. Five-year survival rates for stage I, II, III, and IV were 82.7 54.7, 20.0, and 4.7%, respectively. Statistical analyses identified variables that significantly influenced survival, including lymph node metastasis (p less than 0.01) and distant metastasis (p less than 0.01). Cell type and renal vein involvement did not influence survival significantly. The three different forms of therapy (mitomycin therapy vincristine therapy and immunological therapy) did not influence survival significantly, but the beneficial effect of VBL therapy was obtained. PMID- 1755416 TI - [Epidermal growth factor in the urine of patients with renal cell carcinoma and bladder tumor]. AB - We evaluated the concentrations of immunoreactive epidermal growth factor (EGF) in urine samples from 14 patients with renal cell carcinoma, 16 patients with bladder tumor and 43 non-malignant controls by using radioimmunoassay. In the non malignant controls, urinary EGF excretion significantly decreased with age (r = 0.46, p less than 0.01), and females excreted significantly more EGF than males [16.3 +/- 7.6 and 9.9 +/- 6.0 (mean +/- SD) ng/mg.creatinine; p less than 0.05]. There was no significant difference between urinary EGF excretion in the patients with renal cell carcinoma and non-malignant controls matched for sex and age (15.9 +/- 12.0 and 14.5 +/- 7.9 ng/mg.creatinine). The difference in excretion of EGF between the patients with bladder tumor and non-malignant controls also was not significant (9.9 +/- 5.6 and 11.7 +/- 7.0 ng/mg.creatinine). These findings indicate, that urine EGF has little usefulness as a tumor marker for renal cell carcinoma and bladder tumor. PMID- 1755417 TI - [Treatment of 300 patients with bladder cancer]. AB - From September 1973 to September 1989, 300 patients with bladder cancer were treated at the Department of Urology, Hyogo College of Medicine. They were 231 males and 69 females with an average age of 65.3 years old. The overall 5-year survival rate (Kaplan-Meier's method) was 64.7%. The 5-year survival rates were not different between male patients and female patients, or between patients with single tumor and patients with multiple tumors. Patients with vesical irritation symptoms had more unfavorable prognosis than patients with painless hematuria. Size and configuration of the tumors also affected the prognosis. Histological diagnosis was transitional cell carcinoma in 291 patients, squamous cell carcinoma in 7 patients, adenocarcinoma in one patient and undifferentiated carcinoma in one patient. In patients with transitional cell carcinoma, the 5 year survival rates according to histological grades were 93.5% for G1, 77.8% for G2 and 31.6% for G3. The 5-year survival rate according to clinical stage was 94.4% for Ta, 79.7% for T1, 66.7% for Tis, 46.1% for T2, 38.5% for T3 and 26.6% for T4. Transurethral resection of bladder tumor (TUR-b.t.) was performed in 208 patients as an initial operation and the 5-year survival rate in these patients was 78.6%. The 5-year survival rates for total cystectomy (52 patients), partial cystectomy (6 patients) and simple tumor resection (4 patients) were 51.9%, 25.0% and 37.5%, respectively. These findings suggest that superficial tumors (Ta, T1) can be controlled with TUR-b.t. but infiltrating tumors (T2, T3, T4) should be treated more vigorously with multidisciplinary approaches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755418 TI - [Clinical study of voiding disorders in patients with cerebrovascular accidents]. AB - Cystometry and urethral pressure profile were determined in 41 patients (29 males and 12 females) with voiding disorders resulting from cerebrovascular accidents within one year after the episode. By clinical symptoms, they were classified into 3 groups, urge incontinence (14 patients, 34%), pollakisuria (10 patients, 24%) and dysuria (17 patients, 41%). Cystometrogram were classified into 3 types, hyperactive bladder (31 patients, 76%), normal bladder (5 patients, 12%) and hypoactive bladder (5 patients, 12%). All patients in both groups of incontinence and pollakisuria showed hyperactive bladder except one normal bladder, while in the group of dysuria 3 types of cystometrograms were observed. Bladder capacity in incontinence group showed tendency to be smaller than that in dysuria group who had hyperactive bladder. Maximum urethral pressure in incontinence group was significantly lower than that in pollakisuria group and dysuria group who had hyperactive bladder. Ten patients with cerebral cortical lesions (80%) showed hyperactive bladder and 60% of them showed incontinence. In patients with cerebral lesions who had hyperactive bladder, the maximum urethral pressure of patients with incontinence showed tendency to be lower than that of patients with pollakisuria and dysuria. The majority of 7 patients with thalamic lesions showed hyperactive bladder and normal urethral pressure, and had dysuria. Two patients with pontine lesions showed hypoactive bladder. These findings suggested that urge incontinence resulting from cerebrovascular accidents was due not only to hyperactive bladder but also to lower urethral pressure. PMID- 1755419 TI - [Statistical analysis of the prostatic cancer patients detected from 1985 to 1989 in and around Gunma prefecture]. AB - Prostatic cancer is one of the most common malignant tumors in the field of urology. The number of patients is increasing rapidly and its importance as a mortal disease is gathering attention. In 1985, we organized a registration system for prostatic cancer patients found in and around Gunma prefecture. In this study, we analyzed the clinical characteristics of the 730 patients registered from 1985 to 1989. The results were as follows. Mean age was 74.0 years old and the number of the patients was the greatest in the eighth decade. Voiding disturbance was the most common chief complaint, followed by pollakisuria, gross hematuria and miction pain. Stage and grade distribution were as follows. Stage A 16.2%, B 21.1%, C 17.0%, D 45.7%, well differentiated 27.4%, moderately differentiated 48.2% and poorly differentiated 24.5%, respectively. A statistically significant relationship between stage and grade was observed. Bone was the most common metastatic site. The highest incidence of bone metastasis was in lumbar vertebra, followed by ribs, ilium, thoracic vertebra and ischium. The value of PAP, ALP and ESR tended to be higher in high stage patients, and that of Hb was lower. Fifty two patients were detected by mass screening. Most of these patients were in an early stage. Most of the patients were treated by hormonal therapy. LH-RH agonists constituted 39.2% of the cases given hormonal therapy. PMID- 1755420 TI - [Fundamental study on the collection of prostatic fluid using catheter]. AB - The catheter for expressed prostatic secretions (EPS) collection was newly developed for the purpose of protecting EPS from the contamination of the urethral bacteria. This catheter is blind-ended, and has several lateral windows and a balloon between the end and the windows. The procedure of EPS collection using this catheter is as follows; first the catheter is inserted into the urethra, then a balloon is blown up. The catheter is extracted during massage of the prostate and finally EPS is aspirated through the internal lumen of the catheter. In 23 male patients who had neither urinary tract infection nor genital infection, this catheter method was carried out. Before inserting the catheter, the urethral swab was obtained, then culture of the swab and the EPS was done. The catheter method protected against contamination with bacteria in 56%, with Ureaplasma urealyticum in 40%, and all contaminations in 44% of all cases. PMID- 1755422 TI - [Clinical study on acute scrotum]. AB - Between April 1986 and July 1990, we experienced 13 cases of acute scrotum with surgical exploration. Six of the patients had torsion of the spermatic cord; three had torsion of an appendix of the epididymis, one had torsion of a testicular appendix, one had testicular rupture, one had acute epididymitis and one was normal. Their ages ranged from 3 months to 55 years (mean: 17.7 years), and the patients with torsion of the spermatic cord ranged from 5 to 25 years in age (mean: 16.3 years). No specific symptoms, signs, or laboratory findings were noted in patients with torsion of the spermatic cord. In the majority of cases, scrotal swelling and redness of the scrotal skin were present, and we could not distinguish parts of the scrotal contents. From 2 to 92 hours had passed before the patients presented, and patients who first attended other clinics tended to be treated in an inappropriate manner. Orchidopexy was performed in all patients with torsion of the spermatic cord. At present, only one testis which was treated after a delay of 92 hours has proven to be atrophic. Early consultation of a urological clinic and early surgical exploration are important in the treatment of the acute scrotum. PMID- 1755421 TI - [Clinical study of new technique for collection of EPS, prostate catheter method- comparison with Meares and Stamey's method]. AB - We newly developed a catheter for expressed prostatic secretions (EPS) collection and examined whether or not EPS can be collected with this catheter without contamination of urethral bacteria. The clinical value of the prostate catheter method was examined in comparison with Meares & Stamey's method. Both prostate catheter and Meares & Stamey's method were performed by crossover method in 11 patients who were highly suspected of chronic prostatitis based on symptoms and physical findings. Three of the 4 cases of bacterial prostatitis on Meares & Stamey's method were diagnosed as bacterial prostatitis by the prostate catheter method, but the remaining one was diagnosed as prostatodynia. One of the 3 cases of non-bacterial prostatitis on Meares & Stamey's method was diagnosed as non bacterial prostatitis, but the other two cases were diagnosed as urethritis. Four cases of prostatodinia on Meares & Stamey's method were given the same diagnosis by the prostate catheter method. In conclusion, eight of 11 cases received the same diagnosis by the two different method. The remaining three cases were given different diagnosis, but the prostate catheter method gave a more accurate diagnosis. We concluded that the prostate catheter method is useful in the differential diagnosis of bacterial prostatitis and non-bacterial prostatitis. PMID- 1755423 TI - [Ureaplasma urealyticum and mycoplasma hominis in male urethritis]. AB - We conducted a multi-center clinical study to evaluate the role of Ureaplasma urealyticum and Mycoplasma hominis in male urethritis. The incidence of each organism in first-voided urine samples of 160 male urethritis patients, including 28 with gonococcal and 126 with non-gonococcal urethritis, was investigated. U. urealyticum and M. hominis were isolated from 13.6% and 6.5%, respectively, of the urine samples, and the concentration of each mycoplasma exceeded 10(3) ccu/ml (color changing units/ml) in 5.2% and 3.9%, respectively. Among 64 patients with non-gonococcal non-chlamydial urethritis, U. urealyticum and M. hominis concentration exceeding more than 10(3) ccu/ml were detected in only two and one samples, respectively. The incidence among urethritis patients with a concentration of either mycoplasma exceeding 10(3) ccu/ml was not significantly greater than that among subfertile males without urethritis. The findings of the present study suggest that, although mycoplasmas may cause urethritis in some patients, the incidence of urethritis due to U. urealyticum or M. hominis is low among patients with non-gonococcal, non-chlamydial urethritis. PMID- 1755424 TI - [Renal pseudoaneurysm successfully treated by superselective embolization as a complication of percutaneous nephrolithotomy: report of a case]. AB - A case of renal pseudoaneurysm which occurred as a complication of percutaneous nephrolithotomy (PNL) for right renal staghorn calculi is presented. A 59-year old man, who previously had left nephrectomy due to renal staghorn calculi and right pyelolithotomy due to renal calculi, was admitted to our hospital for treatment of recurrent right renal staghorn calculi on March 29, 1990. Laboratory data on admission revealed no significant abnormality except for a mild elevation on blood glucose (116 mg/dl). Pseudomonas aeruginosa (10(6) CFU/ml) was cultured from urine. Preoperative plain abdominal film showed right partial staghorn calculi extending to the lower calyx and pelvis. Three sessions of PNL were performed. Two nephrostomy tubes were placed in the upper and middle calyces at the first session. Although all calculi were removed completely, massive renal bleeding with bladder tamponade occurred several times postoperatively and blood transfusion was necessary. Renal angiography was performed, and it was demonstrated renal pseudoaneurysm at the upper nephrostomy tract. At the same time the pseudoaneurysm was treated by superselective embolization with an absorbable gelatin sponge. We reviewed the related literature on complications of PNL. Etiology and treatment of a renal vascular injury associated with PNL are also discussed. PMID- 1755425 TI - [A case of synchronous ipsilateral renal cell carcinoma and transitional cell carcinoma]. AB - A case of synchronous ipsilateral renal cell carcinoma with renal pelvic and ureteral transitional cell carcinoma is reported. A 80-year-old man, who had had transurethral resection of bladder tumor three times, was admitted on August, 1989 for recurrence of bladder tumor. Excretory pyelography revealed a filling defect of left renal pelvis. Findings of retrograde pyelography and computed tomography were in accord with those of the excretory urograms. Under a diagnosis of the left renal pelvic and ureteral tumor associated with the bladder tumor, left nephroureterectomy with bladder cuff resection was performed. Pathological diagnosis was renal pelvic and ureteral transitional cell carcinoma with renal cell carcinoma, which existed incidentally in the same kidney. Double unrelated primary carcinoma in urinary tract, especially, double dissimilar primary carcinoma in the same kidney, is rare. To our knowledge, this case is the 20th double cancer in upper urinary tract reported in Japan. PMID- 1755426 TI - A case large protruding cystitis glandularis: clinical, histological and mucin histochemical study. AB - A case of large protruding cystitis glandularis is reported. A 36-year-old man was admitted to our hospital due to acute cholecystitis, and large protruding masses were incidentally found in the urinary bladder by abdominal ultrasonography. The histological study revealed that they consisted of a large number of Brunn's nests with or without cysts which were often accompanied with columnar epithelial metaplasia, and of glandular structures closely resembling the colonic crypts. The mucin-histochemical study demonstrated glandular lesions in the bladder secreted colonic type mucin, and endocrine cells positive with Grimelius' staining. A review of literature disclosed 19 clinical cases of cystitis glandularis, since 1970, in Japan, but such a large protruding lesion as this case is rare. We first performed detailed histological and mucin histochemical studies for this clinical case. PMID- 1755427 TI - [Foreign body stone of the ureter as a complication of acupuncture: report of a case]. AB - A 47-year-old female was admitted to our clinic with the suspicion of ureteral foreign body. She had undergone acupuncture for left lumbago twelve years earlier. Plain X-ray film revealed a linear shadow and calcified shadows laterally to left third lumber vertebra. Computed tomographic scan and pyelogram showed them located in the left ureter. Left ureterolithotomy was performed successfully. The removed stone was accompanied by an acupuncture needle. Including our case, twelve cases of foreign bodies as a complication of acupuncture in the upper urinary tract reported in the Japanese literature were reviewed. PMID- 1755428 TI - [Intrascrotal and seminal vesicular granuloma probably induced by propionibacterium acnes]. AB - A case of right intrascrotal and seminal vesicular granuloma probably induced by Propionibacterium acnes is reported. A 62-year-old man was admitted to our department because of low grade fever and the right intrascrotal and retrovesical masses without tenderness. Ultrasonography computed tomography, magnetic resonance imaging and vesiculography suggested a neoplasm. However, leukocytosis and high erythrocyte sedimentation rate (ESR) and c-reactive protein level (CRP) suggested inflammatory disease. He was treated for 1 week with parenteral cefazolin (CEZ) (4 g/day), and the intrascrotal mass was remarkably reduced in size. To rule out neoplasms, right orchiectomy and needle biopsy of the right seminal vesicle were performed and nonspecific chronic granuloma was identified histologically. On the 5th postoperative day he developed fever (39.2 degrees C) and P. acnes was isolated from blood culture. Gram stain revealed gram-positive rods in the specimen. Further chemotherapy normalized levels of ESR and CRP and white blood cell count and reduced the right seminal vesicle to its normal size. Recently several cases of infection induced by P. acnes have been reported, but this is the first report in the genitourinary tract. PMID- 1755429 TI - [Laboratory and clinical study of sulbactam/cefoperazone (SBT/CPZ) on bacterial prostatitis]. AB - The cefoperazone and sulbactam concentrations in human prostatic fluid were measured following intravenous administration of sulbactam/cefoperazone (SBT/CPZ) and its clinical efficacy and safety in the treatment of 11 patients with acute or chronic bacterial prostatitis were evaluated. Cefoperazone concentrations in prostatic fluid (PF) one hour after an intravenous infusion of SBT/CPZ at a dose of 1 g and 2 g were 0.57 +/- 0.26 micrograms/ml and 1.37 +/- 0.86 micrograms/ml, respectively, both exceeding the MIC against most of the isolated strains from expressed prostatic secretion (EPS). The sulbactam levels in PF at doses of 1 g and 2 g of SBT/CPZ were 0.30 +/- 0.18 micrograms/ml and 0.38 +/- 0.13 micrograms/ml, respectively, both of which were high enough to potentiate antimicrobial activity of cefoperazone. The peak of MIC distribution of sulbactam/cefoperazone against E. coli (14 strains) and S. epidermidis (21 strains) isolated from EPS of patients with bacterial prostatitis was in a range of 0.1-0.2 micrograms/ml and 0.2-0.78 micrograms/ml as described for the cefoperazone concentration, respectively, which were superior to those of cefoperazone, ceftazidime and piperacillin, all compared as control, SBT/CPZ exhibited 8 fold or more potent antimicrobial activity than cefoperazone against beta-lactamase producing E. coli and CNS. Clinically, SBT/CPZ was given to 11 patients diagnosed as having bacterial prostatitis in a daily dose of 2-4 g for 5 to 8 days. The drug was found to be effective in all (100%) of 5 patients with acute prostatitis and in 3 (75.0%) of 4 patients who were judged to be assessable among 6 chronic patients. No side effects of any kind were observed in any of the patients treated. In laboratory tests, a transient thrombocytopenia was reported for one patient. SBT/CPZ is particularly useful in the treatment of acute bacterial prostatitis caused by GNR. This drug is useful for chronic prostatitis those, caused primarily by CNS which is susceptible to this agent. This drug is available as an injectable form, subjects for its appropriate usage will be those who show acute exacerbation of infection or who do not respond to oral therapy. PMID- 1755430 TI - Prevention-centered science in mental health. AB - Provides an overview of the Preventive Intervention Research Center (PIRC) Program, and an introduction to the nine papers of a special issue of AJCP. Discusses major problems faced by prevention researchers and ways in which the PIRCs are structured to address some of these problems. Highlights the importance of rigorous prevention experiments as tests of theory, and therefore as critical components of the scientific continuum. PMID- 1755431 TI - The use of structural equation modeling in generative research: toward the design of a preventive intervention for bereaved children. AB - Describes a generative study of processes which may lead to symptomatology in children who have experienced the death of a parent. Based on existing literature, four putative mediating variables were identified: parental demoralization, family warmth, negative family events, and positive stable family events. Structural equation modeling techniques were used to compare several potential causal models involving these variables. The results were most consistent with a model in which bereavement was not directly related to the child symptomatology, but rather its effects were transmitted through these four mediational mechanisms. The implications of the results of the structural modeling for the design and evaluation of preventive interventions are discussed briefly. PMID- 1755432 TI - Epidemiology and preventive interventions: parental death in childhood as a case example. AB - Illustrates how standard epidemiologic principles form the knowledge base to justify a preventive intervention for an at-risk population. These principles were applied to a sample of 92 from the population of children aged 8 to 15 at alleged risk for mental health disorders because a parent died. Prior work on this alleged risk population is sparse and flawed. Validly determining the population effect of an alleged risk factor requires assessing the influence of sampling bias. The bias found, underrepresentation of deaths of a mother, did not influence the relations among death of a parent and children's depression and conduct disorder, and the modifiable mediators of risk to be changed by the preventive intervention. The epidemiologic measure of effect indicated that death of a parent is a risk factor for major depression but not for conduct disorder among youth. Families recruited for the preventive intervention by epidemiologic methods (ES families) did not differ significantly from the earlier families on whom the knowledge base was formed. Families referred to the intervention by self or others significantly differed from the ES families in two ways that constituted serious biases. The implications of these biases for prevention were discussed. PMID- 1755433 TI - Stability and quality of life events and psychological symptomatology in children of divorce. AB - Studied the relations between postdivorce events and maladjustment of children of divorce using a two-dimensional model of events. One dimension concerned the stability of events and included whether they were increases, decreases, or the continuation of stable conditions. The second dimension was quality, and included whether they had a positive or negative valence. Two samples of children of divorce (ns = 142 and 64) ages 8-15 were studied. Children's overall maladjustment as reported by children and parents were the criterion variables. Scores were derived from a life events schedule for children of divorce to assess the occurrence and stability of positive and negative divorce-related events. The relations between event scores and maladjustment were different when children's self-reports and parent reports were used as criterion. In predicting children's self-reported maladjustment (a) stable positive events but not changes in positive events were related to lower maladjustment (b) increased negative events were related to higher maladjustment, and (c) change for the worse was related to higher maladjustment. In predicting parent reports of children's maladjustment, only the relations of the change for the worse score were replicated. Implications of the results for the design of preventive interventions and for the study of children in stressful situations are discussed. PMID- 1755434 TI - Factors facilitating adjustment to unemployment: implications for intervention. AB - Conducted a community survey in the Fall of 1984 in a sample of high unemployment blue-collar census tracts in southeastern Michigan. Results of earlier analyses using these data showed that involuntarily unemployed workers had significantly elevated levels of depression, anxiety, somatization, and self-reported physical illness relative to a stably employed comparison group (Kessler, House, & Turner, 1987). Results presented in this paper document that this relationship is modified by social support (as measured by social integration and the availability of a confidant), self-concept, and various coping processes. Further analyses allowed us to determine the way in which these modifiers operate. The modifying effects of social support and coping operate primarily by buffering the impact of unemployment-related financial strain on the health outcomes. Self concept operates primarily by attenuating vulnerability to other stressful life events. The implications of these results for the design and implementation of preventive interventions are discussed. PMID- 1755435 TI - From field experiments to program implementation: assessing the potential outcomes of an experimental intervention program for unemployed persons. AB - Demonstrated a procedure suggested by Bloom (1984) to provide estimates for the effects of an intervention on its actual participants compared to global effects on study participants in the intervention group, whether or not they showed up. Analyses were based on data collected in a field experiment that tested a preventive intervention for unemployed persons (Caplan, Vinokur, Price & van Ryn, 1989). Effect size estimates were two to three times larger for the actual participant group than for the entire experimental group on employment outcomes (e.g., earnings) and mental health (anxiety and depression). Further analyses produced results showing that compared to participants, the nonparticipants achieved significantly higher levels of reemployment at posttests and did not differ significantly from participants on all other outcomes. The results suggest that persons who most needed the intervention and benefited from it were drawn into it through self-selection processes. PMID- 1755436 TI - Developmental epidemiologically based preventive trials: baseline modeling of early target behaviors and depressive symptoms. AB - Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials. PMID- 1755437 TI - Effect of first-grade classroom environment on shy behavior, aggressive behavior, and concentration problems. AB - Investigates the effect of the first-grade classroom environment on the shy behavior, aggressive behavior, and concentration problems of 609 children in 19 East Baltimore public schools. First-grade classroom environment was assessed in terms of dominant pattern of classroom achievement and behavior. Structured teacher ratings assessed child shy behavior, aggressive behavior, and concentration problems at the end of first grade. Children in low-achieving classroom environments had significantly higher teacher ratings of shy behavior and aggressive behavior than children in mixed-achieving or high-achieving environments, even after controlling for potentially confounding child characteristics and classroom behavior environment effects. Analyses controlling for child characteristics and classroom achievement environment effects indicated that children in poor-behaving classroom environments also had significantly higher teacher ratings of shy behavior than children who were not in poor behaving environments. Subgroup analyses indicated that repeaters in mixed achieving environments had significantly higher levels of shy behavior compared with nonrepeaters, and repeaters in poor-behaving environments had significantly higher levels of aggressive behavior compared with nonrepeaters. Implications for prevention research are discussed. PMID- 1755438 TI - Who enrolls in prevention trials? Discordance in perception of risk by professionals and participants. AB - Internal and external validity problems permeate all intervention studies but are accentuated in primary preventive intervention research, particularly when studies target or recruit individuals based on their risk for psychopathology. Since many people who are at risk do not yet experience distress, they may not perceive the need for intervention. Recruitment tactics based on explaining extent of risk are unlikely to be persuasive and may have negative consequences. If respondents are not motivated to participate, a small or biased subset of the target population will participate in the intervention. Bias is of special concern when those enrolled represent only part of the continuum of risk. Selective enrollment may compromise both internal validity (the interpretation of the research results) and external validity (the generalizability of the findings) of intervention trials in primary prevention. This article discusses the effects of partial enrollment and the resultant bias. It suggests several strategies for increasing the enrollment of the target population and examines some of their ethical ramifications. It also stresses the importance of collecting systematic data documenting how the participants in the intervention differ from the target group as a whole. PMID- 1755439 TI - Reinventing fidelity: the transfer of social technology among settings. AB - In an ideal world, effective programs would be disseminated on a large scale, but many obstacles block program diffusion. To date, little guidance has been provided by program designers on how to implement the program in different sites with different personnel and client populations. This article discusses the debate between the "fidelity camp" and the "reinvention camp" and suggests an approach that reconciles the two positions: fidelity should be maintained to the program's mechanism of operation; reinvention is permitted in implementation if the causal mechanism is preserved. Such an approach is essential for effective dissemination of preventive interventions that are successful in controlled trials. PMID- 1755440 TI - Invited commentary: common wisdom and plain truth. PMID- 1755441 TI - The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial. AB - The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation. PMID- 1755442 TI - Anthropometric predictors of coronary heart disease and total mortality: findings from the US Railroad Study. AB - Prospective data from the US Railroad Study were used to investigate the relations of several anthropometric variables to coronary heart disease and all cause mortality in males initially free of cardiovascular disease. Middle-aged men were examined in 1957-1960 and followed until 1977 or death. Anthropometric indicators of total body fat (body mass index and the sum of the subscapular and triceps skinfolds) and central body fat (the ratios chest circumference/biacromial (shoulder) diameter, and chest circumference/standing height) were significantly and directly associated with age-adjusted coronary heart disease mortality. When systolic blood pressure, serum cholesterol, cigarette smoking, and vital capacity were also taken into account, the ratio chest circumference/biacromial diameter remained significantly associated with coronary heart disease mortality. Total, central, and peripheral body fat had a "U"-shaped relation with all-cause mortality. Measures of the ratio of central to peripheral body fat were inconsistently related to mortality. These results indicate that certain anthropometric measurements, especially those that may indicate central adiposity, are positively related to the development of fatal coronary heart disease and quadratically related to all-causes death rates. PMID- 1755443 TI - Trend in serum total cholesterol level in 110,000 young adults in The Netherlands, 1974 to 1986. AB - Data from two screening projects on cardiovascular risk factors were used to analyze the trend in serum total cholesterol level in the Netherlands between 1974 and 1986. Cholesterol levels were measured in a single reference laboratory of the World Health Organization throughout the entire study period. Between 1974 and 1980, about 30,000 men and women aged 37 to 43 years (mean age, approximately 40 years) were screened. A decrease in mean serum total cholesterol level was observed until the end of 1977, when it was followed by an increase. This resulted in a net change over the entire study period of -0.07 mmol/liter (3 mg/dl) in men and -0.03 mmol/liter (1 mg/dl) in women. Between 1981 and 1986, about 80,000 men aged 33 to 37 years (mean age, 35 years) were screened. During this period, a decrease of 0.20 mmol/liter (8 mg/dl) in the mean total cholesterol level was observed. In spite of the decline in the mean total cholesterol level, the prevalence of cholesterol values of greater than or equal to 6.5 mmol/liter (greater than or equal to 251 mg/dl) in young adult men was still high in 1986 (16 percent). A further reduction is therefore desirable. The decline in the mean total cholesterol level in young adults might indicate that a further decline in mortality from coronary heart disease can be expected. PMID- 1755444 TI - Relation of blood pressure to cognitive function in the elderly. AB - Clinical case-control studies of the relation between blood pressure and cognitive function have generally found lower function among hypertensives. Most of these studies were small and incompletely controlled for confounders. Two population-based studies have yielded conflicting results. This study examines cognitive function over the entire range of blood pressure in a defined elderly population. A questionnaire administered in the home to 3,809 persons aged greater than or equal to 65 years in East Boston, Massachusetts, in 1982 and 1983 contained four brief cognitive tests: immediate memory, delayed memory, a mental status questionnaire, and digit span. In linear regression analyses adjusting for age, sex, and education, the direction of the association was not consistent among the tests. An increase in diastolic pressure of 10 mmHg was associated with an increase of 1.0 in percentile scores on the immediate memory test (95% confidence interval (CI) -0.04 to 1.9); with an increase of 1.1 in percentile scores on the delayed memory test (95% CI -0.1 to 2.3); with a decrease of -0.8 in percentile scores on the mental status questionnaire (95% CI -1.8 to 0.2); and with a decrease of -0.9 in percentile scores on the attention test (95% CI -1.5 to -0.2). These results suggest that blood pressure is not a substantial contributor to cognitive status in the elderly. PMID- 1755445 TI - Identification of risk factors for diethylstilbestrol-associated clear cell adenocarcinoma of the vagina: similarities to endometrial cancer. AB - This epidemiologic case-control study describes risk factors for clear cell adenocarcinoma of the vagina among 106 cases and 447 controls with in utero exposure to diethylstilbestrol (DES). Controlling for age, socioeconomic status, and time during gestation of initial DES exposure, the authors found a significantly increased risk of this cancer in women who were taller or more obese then their contemporaries at age 14-15 years. The relative risk of this cancer for women in the highest tertile for height compared with those in the lowest tertile was 2.5 (95% confidence interval 1.23-4.90). The relative risk from a similar comparison of body mass was 2.8 (95% confidence interval 1.20 6.53). Trend tests indicated that both factors had significant dose-response relations with risk of vaginal clear cell adenocarcinoma. These findings are particularly interesting since height and body mass are risk factors for endometrial cancer. DES-positive cases interviewed more than 10 years after diagnosis were also significantly thinner than cases interviewed less than 7 years after diagnosis (p = 0.01), providing the first evidence that adolescent adiposity level is associated with survival times for women with this disease. PMID- 1755446 TI - Heterogeneity of breast cancer risk in families of young breast cancer patients and controls. AB - Familial heterogeneity of breast cancer risk was assessed among 4,159 first degree female relatives of 1,074 population-based, young breast cancer cases (aged 20-54 years) diagnosed from December 1, 1980 to December 31, 1982 and 4,120 first-degree female relatives of 998 age- and race-matched, population-based controls from the metropolitan Detroit, Michigan, area. The family risk index method used for analysis considers family size, age, and race differences among families in the assessment of family risk. Families of cases showed a higher risk of breast cancer than did families of controls, with case families 1.80 to 4.24 times more likely to be defined as high risk than control families; the magnitude of the risk differential was dependent on the definition of high risk. Within the case families only, familial heterogeneity of risk was suggested, with a small proportion of families (less than 5%) at lower risk of breast cancer than most case families. A number of reproductive risk factors, age, race, and histologic type of cancer for the proband, and several family characteristics were investigated to help characterize the case families at higher and lower risk. PMID- 1755447 TI - A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators. AB - A study of 748 cases and 1,411 hospital and community controls in four Latin American countries evaluated the association between certain elements of diet and invasive cervical cancer. Subjects were interviewed about their adult consumption of 58 food items, including the major sources of putative protective agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other behavioral and medical characteristics related to cervical cancer. Participation rates were above 95% for both cases and controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, and detection of human papillomavirus 16/18 by filter in situ hybridization, a slightly lower risk was observed for the highest quartiles of consumption of fruit and fruit juices, while no reductions in risk were associated with vegetables, foods of animal origin, complex carbohydrates, legumes, or folacin rich foods. When nutrient indices were derived, significant trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs. the lowest quartile; p for trend = 0.003), beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated the association with beta-carotene, while the association with vitamin C remained unchanged. The results are consistent with those of other investigations and provide support for a protective effect of vitamin C, carotenoids, and other substances found in the same fruits and vegetables against the development of invasive cervical cancer. However, the fact that the associations were driven by relation in two of the study sites and among women of higher socioeconomic status leaves open the possibility of selection bias or effects of unidentified aspects of dietary patterns. PMID- 1755448 TI - A case-control study of nutrient status and invasive cervical cancer. II. Serologic indicators. AB - A study of 387 cases and 670 controls from four Latin American countries evaluated the hypothesis that lower serum levels of eight micronutrients were associated with a higher risk of invasive cervical cancer. The serologic analyses were restricted to a sample of subjects with stage I and II disease to minimize effects of the disease on the serologic markers. Ninety-four percent of eligible subjects donated blood samples, which were analyzed for carotenoids, retinol, and tocopherols by high-pressure liquid chromatography. Cases did not differ significantly from controls in mean serum levels of retinol, cryptoxanthin, lycopene, alpha-carotene, lutein, or alpha-tocopherol. The mean level of beta carotene was lower and the mean level of gamma-tocopherol was higher among cases as compared with controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, detection of human papillomavirus types 16/18, cholesterol, and triglycerides, a trend of decreasing risk was associated with higher levels of beta-carotene (p for trend = 0.05), with the adjusted odds ratio decreasing to 0.72 for the highest versus the lowest quartile. beta-Carotene results were similar by stage of disease, which argues against an effect of disease progression on nutrient values. Unexpectedly, increasing risks were observed as the level of gamma-tocopherol increased (odds ratio = 2.09; p for trend = 0.03); however, levels were higher among stage II cases as compared with stage I cases, suggesting a metabolic alteration resulting from the disease process. The concordance in the strength and direction of the blood and dietary results, presented in the accompanying report (Herrero R, Potischman N, Brinton LA, et al., American Journal of Epidemiology 1991;134:1335 46), supports a role for beta-carotene or foods rich in beta-carotene in the etiology of cervical cancer. This study also indicates that simultaneous analysis using serologic and dietary nutrient indicators allows better discrimination of the association. PMID- 1755449 TI - Prevalence, determinants, and consequences of chronic neck pain in Finland. AB - Chronic neck pain is a relatively mild musculoskeletal condition, but common enough to be a possible public health problem. The distribution, determinants, and consequences of chronic neck pain have hitherto been described inadequately. In the Mini-Finland Health Survey, a representative population sample of 8,000 Finns aged greater than or equal to 30 years was invited to participate in a comprehensive health examination comprising an interview and a clinical examination; 90.2% complied. Predetermined criteria were used to diagnose major cardiovascular, musculoskeletal, respiratory, mental, and other disorders, regardless of other simultaneous disorders. Chronic neck syndrome was diagnosed in 9.5% of the men and 13.5% of the women. When adjusted for age and sex, the prevalence of the neck syndrome was associated with a history of injury to the back, neck, or shoulder and with mental and physical stress at work. Among those aged 30 to 64 years, overweight and parity were also significant determinants. Other musculoskeletal and mental disorders were associated with neck syndrome, and the association persisted after working conditions, injuries, overweight, and parity were adjusted for. There was some independent association between neck syndrome and disabilities, use of physician services, and use of pain killers. PMID- 1755450 TI - Natural family planning: current knowledge and new strategies for the 1990s. Proceedings of a conference. Washington, D.C., December 10-14,1990. PMID- 1755451 TI - Natural family planning: looking ahead. AB - Natural family planning is used by a relatively small number of people worldwide. The Institute's goal is to increase the knowledge, availability, effectiveness, and acceptability of natural family planning. To do so, the Institute is conducting biomedical research in several areas including: (1) the development of a home test kit for ovulation prediction, (2) sperm-mucus interaction, (3) the mechanisms and fertility impact of lactational amenorrhea, and (4) outcome of pregnancies in natural family planning users. PMID- 1755452 TI - Fetal outcome among pregnancies in natural family planning acceptors: an international cohort study. AB - This international, multicenter, prospective cohort study examines the outcome of pregnancies associated with aging gametes. Comparing pregnancies conceived at or near the peak mucus phase with those occurring before or after the peak provides a means of evaluating the effect of aging gametes. The outcome criteria are (1) rates of spontaneous abortion, (2) low birth weight, and (3) congenital malformations. Preliminary analysis shows a trend toward increased spontaneous abortion with aging gametes in certain subsets (women with prior pregnancy losses) but no effect on birth weight. Too few method failures have yet been studied to make a definitive statement on congenital malformations. PMID- 1755453 TI - Human cervical mucus: research update. AB - Evaluation of cervical mucus is a standard for determining the fertile period in natural family planning. Cervical mucus accepts, filters, prepares, and releases sperm for successful transport to the egg and fertilization. Recent scientific advances provide answers to how the mucus regulates fertility as its physical properties change during the menstrual cycle. Transmission electron microscopy reveals small interstices between mucus macromolecules relative to a sperm head. Thus advancing sperm must push aside or cut through the microstructure. The interstices are largest in the periovulatory phase of the cycle. Small magnetic spheres, comparable with the size of a sperm head, are now being used to study the physical properties of the mucus on the scale of individual sperm. PMID- 1755454 TI - Symptothermal and hormonal markers of potential fertility in climacteric women. AB - One hundred seventy-seven menstrual cycles in 36 women between 45 and 53 years of age were studied prospectively. All the women were experienced in the symptothermal method of natural family planning. The objective was to determine the symptothermal and hormonal indices of potential fertility by measuring urinary estrone glucuronide and pregnanediol glucuronide. Thirty-three percent had regular cycles consistent with potential fertility, 19% had cycles consistent with infertility, and 47% had a mixture of both types of cycle. PMID- 1755455 TI - Breastfeeding: a natural method for child spacing. AB - Lactational amenorrhea plays an important role in child spacing. Recent research has led to a consensus regarding the status of lactational amenorrhea as a method of family planning. This is currently referred to as the lactational amenorrhea method. Research priorities were to field test the lactational amenorrhea method and define the factors that influence lactational amenorrhea and the interface between the lactational amenorrhea method and other family planning methods. PMID- 1755456 TI - The evolution of reference methods to monitor ovulation. AB - Reference methods to predict or detect ovulation have evolved substantially during the past few decades. The potential use and limitations of such methods are reviewed. The use of transvaginal ultrasonography with color flow mapping to monitor periovulatory changes in the intrafollicular morphology and blood flow is described. PMID- 1755458 TI - Home tests to monitor fertility. AB - Industry has been intimately involved in the development of products used in the monitoring of fertility at home. The perspective of industry and the development of such tests including their rationale are presented. The methods taken by industry to utilize current technology in the development of reliable, rapid, one step tests for urinary human chorionic gonadotropin and luteinizing hormone and the subsequent expansion into other areas are covered. PMID- 1755457 TI - Idiometric assay, the third way: a noncompetitive immunoassay for small molecules. AB - A novel, noncompetitive immunoassay applicable to the measurement of small molecules including ovarian steroids is described. Using monoclonal antibodies with the ability to recognize both beta-typic and alpha-typic binding sites, a new simplified, sensitive, and specific immunoassay system has been developed. The initial work of this development is presented, along with preliminary results for a novel immunoassay for estradiol. PMID- 1755459 TI - A prototype for ovulation detection: pros and cons. AB - A noninstrumented enzyme immunoassay for urinary estrone conjugates was adapted from an instrumented microtiter plate enzyme immunoassay assay. The end point of the assay was a color change from green to clear, which was visible to the unaided eye. The visible color change was adjusted to allow 80 ng/ml estrone conjugates (on the basis of a sample size of 6.5 microliters urine) to be distinguished from an infinite dilution without instrumentation. The evaluation of human urine collected from ovulatory ovarian cycles demonstrated that early follicular phase concentrations (35.9 +/- 6.8 to 79.4 +/- 14.7 ng/ml, n = 10) produced a dark-green color, whereas late follicular phase concentrations (162.9 +/- 20.1 ng/ml, n = 10) produced no color. Daily urine samples throughout 10 ovulatory ovarian cycles produced parallel profiles when compared to measurements of estradiol in paired blood samples. Complete analysis of the data indicated that ovarian follicular dynamics can be accurately monitored through the noninstrumented analysis of daily estrone conjugates in urine samples. PMID- 1755460 TI - Use of the Home Ovarian Monitor in pregnancy avoidance. AB - The application of the Home Ovarian Hormone Monitor to the avoidance of pregnancy by periodic abstinence has been explored. No woman had difficulty with the daily urine testing, and their results consistently identified the distinctive hormone pattern of the ovulatory cycle and the day of ovulation and correlated closely with the mucus symptoms. The tests gave 4 days or more warning of ovulation in 99% of cycles and allowed intercourse to be resumed 1 to 3 days after ovulation in 88%, giving a mean period of abstinence of 7 days. No pregnancy occurred from intercourse during the late safe days defined by the Monitor, but some early-day pregnancies occurred through long sperm survivals of 6 to 8 days, mostly during the return of fertility after breastfeeding. Rules for the avoidance of pregnancy, with the minimum of testing on the basis of these results, are given. PMID- 1755461 TI - Is the lactational amenorrhea method a part of natural family planning? Biology and policy. AB - The lactational amenorrhea method is a natural method of family planning for women who breastfeed their infants. The underlying physiology results in a natural suppression of ovulation, and the concomitant amenorrhea, induced by exclusive (or almost exclusive) breastfeeding. This in addition to the infant's age of 6 months or less and specific feeding pattern are the parameters used to identify the possible return of fertility. The lactational amenorrhea method provides at least 98% protection against pregnancy. Data from a recent multicenter study of breastfeeding support the use of the lactational amenorrhea method as a natural family planning method. The lactational amenorrhea method can be incorporated into natural family planning programs and teaching. PMID- 1755462 TI - The natural family planning--lactational amenorrhea method interface: observations from a prospective study of breastfeeding users of natural family planning. AB - Methods of natural family planning are sometimes difficult for women to use during lactation. When this is so, the lactational amenorrhea method may prove useful. Researchers agree that a fully breastfeeding woman who is amenorrheic is 98% protected from pregnancy for up to 6 months after delivery. The fertility status of 74 users of natural family planning during the time they would have been protected by the lactational amenorrhea method is examined. Underlying hormonal profiles show that there was little ovarian activity during this time. Eight ovulatory events occurred during the period of protection by the lactational amenorrhea method, of which four fulfilled minimum criteria for adequacy; there were no pregnancies during this period. However, some women did report experiencing fertile mucus symptoms during this time that were often unrelated to estrogen production. Using the lactational amenorrhea method rather than natural family planning allows them to avoid unnecessary abstinence. PMID- 1755463 TI - Ultrasonographic patterns of ovarian activity during breastfeeding. AB - In this study, ultrasonography was used to detect follicular activity in lactating women, and these findings were related to the underlying hormonal profiles and to the mucus symptom. A number of different patterns of follicular development were seen before the women returned to normal fertile cycles during the period that was previously considered to be characterized by ovarian quiescence. Some of the transitory patterns of follicular activity were reflected in rising hormone levels and patterns of fertile mucus that were sometimes confusing for these lactating women who were using natural family planning. PMID- 1755464 TI - Ovulation method use during breastfeeding: is there increased risk of unplanned pregnancy? AB - Data from two prospective studies of the ovulation method were used to assess pregnancy rates and users' fertility-related behaviors among breastfeeding women. The rate of unplanned pregnancy was less than 1% during the first 6 months of lactational amenorrhea. However, the unplanned pregnancy rate was elevated among breastfeeders during the months after menses return compared with the pregnancy rate during nonlactating cycles. Rates were also elevated at the time when infant feeding supplementation was started. This increase in unplanned pregnancies was not directly attributable to nonadherence to the ovulation method rules; there was some indication that adherence to the rules actually may be increased during those months. Therefore, special emphasis on both the need for improved breastfeeding support to delay menses return and the increased potential for method failure among new users during this period of time should be incorporated into ovulation method training and support programs. PMID- 1755466 TI - Santiago Breastfeeding Promotion Program: preliminary results of an intervention study. AB - A prospective intervention study was undertaken in Santiago, Chile, to assess the impact of a breastfeeding promotion program and the acceptance and use of the lactational amenorrhea method for natural child spacing. The intervention study significantly increased the duration of exclusive breastfeeding and amenorrhea. In addition, the use of the lactational amenorrhea method proved highly efficacious, with an unplanned pregnancy rate of less than 0.5% by 6-month cumulative life table. Total family planning coverage at 6 months was increased in the intervention group. PMID- 1755465 TI - Efficacy of the symptothermal method of natural family planning in lactating women after the return of menses. AB - This study was designed to determine the efficacy of the symptothermal method of natural family planning during lactation. Although the method appears to give a reasonable reflection of fertility potential over time, it overlaps with the profound influence of lactation in both ovulation suppression and the delay of luteal phase adequacy. Further analysis is planned to attempt to identify those particular mucus signs and symptoms that are helpful during the transition from lactational amenorrhea to normal cycling. PMID- 1755467 TI - Natural family planning use-effectiveness and continuation. AB - Numerous studies have been conducted to assess the use-effectiveness of natural family planning. However, because of imprecise definitions of terms, these studies show noncomparable results. Special effort is required to study natural family planning use-effectiveness by the same criteria as other family planning methods. PMID- 1755468 TI - Efficacy studies in natural family planning: issues and management implications illustrated with data from five studies. AB - Studies of method effectiveness must be carefully assessed for comparability of findings. Several parameters are identified that are important in the assurance of comparable results. This article discusses these issues with the use of data from previously published studies and emphasizes the management implications of use-effectiveness data. PMID- 1755469 TI - Effectiveness and acceptibility of the symptothermal method of natural family planning in Germany. AB - Throughout Germany, 851 women who were instructed in natural family planning participated in a prospective study. Of these, 255 women with 3174 cycles used only natural family planning for family planning and 274 women with 3995 cycles occasionally used barrier methods in the fertile phase. For natural family planning--only users, the Pearl rate for unplanned pregnancy was 2.3 and for mixed-method users 2.1. Most pregnancies resulted from unprotected intercourse during the fertile phase, and the use of barrier methods does not reduce risk taking. PMID- 1755470 TI - Further analysis of contraceptive failure of the ovulation method. AB - Reanalysis of data on the ovulation method of natural family planning collected by the World Health Organization yields the following conclusions. The method is effective during perfect (correct and consistent) use, with a first-year probability of failure of 3.4%. However, it is extremely unforgiving of imperfect use, with a first-year probability of failure of 84.2% if the method is not used correctly. During the initial year, 87% of the cycles were characterized by perfect use. Nevertheless, the 13% of cycles characterized by imperfect use had a tremendous impact on the overall failure rate. During the first year of typical use 22.5% of the women in the clinical trial became accidentally pregnant. PMID- 1755471 TI - Factors related to autonomy and discontinuation of use of natural family planning for women in Liberia and Zambia. AB - From 1983 to 1988, natural family planning programs were conducted in Liberia and Zambia. In Liberia 1055 and in Zambia 2709 women used natural family planning to avoid pregnancy. These users could become pregnant, discontinue use of the method, or become autonomous users. Women who changed intention did not stop use of natural family planning and were not treated as discontinuations. In a multivariate analysis, client's age, breastfeeding status, employment, urban/rural residence, time of registration in the program, and visit intensity were significantly associated with the outcomes. The most consistent association was that women who entered the programs in the later time periods were more likely to become autonomous users and less likely to discontinue use of the method or to experience an accidental pregnancy. PMID- 1755472 TI - Measuring natural family planning in terms of couple-years of protection. AB - Couple-years protection is a summary index of contraceptive protection. Couple years protection allows comparisons of natural family planning with other methods. One couple-year protection for condoms is equal to 1 couple-year protection for pills and 1 couple-year protection for natural family planning. Critical in the calculation of couple-year protection for natural family planning is average duration of use. A working group on natural family planning recommended that 2 years of use be used as average duration until more data are available. PMID- 1755473 TI - The modified mucus method in India. AB - The modified mucus method-Prajanan Jagriti (fertility awakening) is intended to serve the cultural needs of illiterate and semilliterate women. Over 10 months, 3003 women in northern India were taught the modified mucus method. There were a total of 42 pregnancies in 24,702 cycles for a Pearl index of 2.04. High effectiveness is attributed to the support that was provided to clients by the instructor. PMID- 1755474 TI - Setting goals for the classroom. PMID- 1755475 TI - Student group approach to teaching using Tuckman model of group development. AB - If health care professionals are to be effective members of an interdisciplinary team of diagnostic specialists, it is critical that their university education equip them for that role. Using Tuckman's four stages of "forming," "storming," "norming," and "performing," university faculty are shown how a group of undergraduate science students can be developed into an organism intent on identifying solutions to problems posed to them (e.g., technical, medical ethical). The use of the group approach enhances maturity, competence, self esteem, and motivation of the students and enables the instructor to delegate appropriate responsibilities to the students. In addition to a sense of achievement, students also reported greater appreciation of the ideas, values, and abilities of their group colleagues. PMID- 1755476 TI - Osmotic properties of cells: a computer laboratory. AB - A computer laboratory has been designed to teach the osmotic properties of cells. One program, CELL.BA, is for the teacher to enter values for the volume of cell water and osmotically inactive material, the concentration of impermeant solute in the cell, and the permeability of the plasma membrane to water and a nonelectrolyte. When the program is protected, students use it as a cell with unknown osmotic properties. They run experiments on the computer with different concentrations of impermeant or permeant solutes or combinations of the two. Changes in cell volume or solute concentration are collected as data and analyzed with the program, PERMEABILITY LAB.BA. This program provides a parameter list, and students try to fit the data that are graphed on the screen by choosing values for the unknown cell parameters and generating model curves. Programs are written for the Macintosh computer. PMID- 1755477 TI - Measurement of gastric secretion as a student teaching exercise. AB - Teaching gastrointestinal physiology to preclinical medical students presents problems in finding suitable practical exercises to demonstrate the physiology of gastric acid secretion. In our course, students measure their own gastric secretory activity by the use of nasogastric tubes. Gastric secretion can be stimulated by insulin-induced hypoglycemia or by pentagastrin, a synthetic gastrin analogue. The time course of the secretory responses, i.e., volume, acid output, and pH, are followed by collecting control and poststimulatory secretions into 15-min samples. The effect of antiulcer drugs, such as cimetidine, can be easily studied in such experiments. The results of these experiments are very reproducible, allowing year-to-year comparisons of treatments. Examples of results of various experimental protocols are shown. We believe this to be a useful class exercise not only because of the excellent results it yields but because of the experience and insights it produces. PMID- 1755478 TI - Ventilatory control (Ventrol) simulation for education. AB - An educational microcomputer-based simulation of respiratory control has been developed. The program contains three major sections: tutorial, stimulation, and unknown testing. The tutorial section provides a brief discussion of the major factors involved in respiratory control. The simulation section provides a menu of variables to demonstrate the effects of altering inspired gases, changing compliance or airway resistance, metabolic acidosis, neural activity, and lesions (including vagotomy) or exercise. The last section of the program allows students to test their understanding of abnormal respiratory and blood gas values. The program has been used as a problem-solving exercise in a medical physiology course. Student groups were assigned to a microcomputer and given a specific problem during a regularly scheduled laboratory period. The students collected data using the program, analyzed and graphed or tabulated the results, and presented their findings in a minisymposium format to their fellow students. This approach has proven valuable and provides a number of pedagogical benefits that are lacking in a lecture-based basic science curriculum. PMID- 1755479 TI - Basic medical physiology: the whole is more than the sum of its parts. AB - In this article we examine the role of basic medical physiology in medical school education. We discuss the historical background, courses in this subject, and methods of teaching it. We conclude that the teaching of medical physiology should emphasize the study of organ systems and of the intact body. The techniques should emphasize meticulous observation, the posing of hypotheses, and the subsequent testing of the hypotheses, i.e., the use of the method used successfully in research. Students should learn the power of the experimental approach and to appreciate the immense variability possible in responses in complex organisms. They should also learn that principles of statistical probability applied logically can detect important differences in data that may be obscured by this variability. They should learn that there are no rigid answers when studying an individual and that they must continue to learn throughout their lives. PMID- 1755480 TI - Performance on multiple choice/short answer tests is not a sufficient criterion for evaluating the educational value of live animal laboratories in the teaching of physiology. PMID- 1755481 TI - Human situations: a course introducing physiology to medical students. AB - A block course of 12 days is described. It is considered to be appropriate for both physiologically naive and sophisticated students entering either a traditional or a problem-based curriculum. It is adaptable for medical schools in both developed and developing countries. Six problem-based small-group sessions, based on everyday human situations, are the core of the course. They are supplemented by a lecture series, laboratory experiments using student volunteers as subjects, laboratory demonstrations, and patient presentations. Student assessment is carried out by criterion-referenced examinations using take-home assignments, oral examinations, and a multiple-choice test containing context dependent questions. The course is well received by students and faculty. Pre- and posttesting show that all students acquire a basic understanding of physiological control systems and of homeostatic mechanisms as they operate in intact human beings. PMID- 1755482 TI - [Current aspects of ultrasonic diagnosis of multiple pregnancy]. PMID- 1755483 TI - [Use of transvaginal echography in early pregnancy]. PMID- 1755484 TI - [Effect of fetal behavioral reactions and respiratory movements on the blood flow in the ductus arteriosus]. AB - Relationship between blood flow velocity waveform and fetal behavioral states was studied in 16 normal pregnancies at 37 to 38 weeks' gestation. The peak flow velocity has demonstrated a statistically significant reduction during active sleep, as against that in quite sleep. These data reflect reduced ductal flow and suggest a redistribution in the left-ventricular and right-ventricular output in favor of the left side of the heart during active sleep. In a prospective cross sectional study of 49 pregnancies (50 fetuses) between 25th and 38th weeks an exponential increase in breathing-related ductal blood flow velocity modulation was observed with advancing gestational age, reflecting the developing pulmonary vascular bed. Fetal ductal flow velocity waveforms were also recorded in 13 cases of prolonged severe oligohydramnios after membrane rupture before 28 weeks' gestation. Normal ductal blood flow velocity modulation values were associated with normal neonatal lung performance, whereas reduced blood flow velocity modulation values were associated with pulmonary hypoplasia. Fetal breathing related ductal flow velocity modulation appears to be a promising predictor of neonatal lung performance. PMID- 1755485 TI - [Doppler-echocardiographic study of intracardiac hemodynamics in intrauterine fetal growth retardation]. AB - Presents the results of Doppler echocardiographic examination of fetal hemodynamics, carried out in 90 women with normal pregnancy and small-for-date fetuses. Analyzes the specific features of fetal intracardiac blood stream in asymmetric and symmetric forms of development retardation. Discloses the regularity in changes of the ventricular diastolic function index in relation to placental resistance growth and of the maximal rate of transvalvular blood stream. Defines the Doppler echocardiographic signs of decompensation of myocardial contractility in conditions of high peripheral vascular resistance. Makes a conclusion on the relationship between changes of cardiac hemodynamics and centralized blood supply in small-for-date fetuses. PMID- 1755486 TI - [Status of the cardiovascular system of the fetus and newborn infant in different degree of severity of maternal hypertensive syndrome]. AB - Examinations of 260 pregnant women with hypertensive syndromes and their 60 full term newborns, carried out with the use of echography of the umbilical artery, umbilical vein, aorta, and internal carotid artery of the fetus have demonstrated a high informative value of these methods for the assessment of the type of fetal condition and prediction of the newborn's adaptive mechanisms of the cardiovascular system. Significant changes of the cardiovascular system were revealed in small-for-date fetuses and in chronic fetal hypoxia, as well as functional changes in the newborns of the mothers with the hypertensive syndrome, with born signs of intrauterine suffering. These changes should be borne in mind when predicting the development of infants born of mothers with the hypertensive syndrome. PMID- 1755487 TI - [Echographic evaluation of the structure and size of the kidneys in healthy newborn infants in the first week of life]. AB - Echographic assessment of the renal structure and size was carried out in 39 healthy full-term babies during the first five days of their lives. Renal echograms of the examined newborns were characterized by highly echogenic cortical layer, ++hypo-echogenic central sinus, and unechogenic pyramids well imaged against the background of the cortical layer. A drastic increase of the echogenicity of some pyramids (3-5) was seen in 4 newborns on days 2-3 of life, not involving impairments of renal function. No differences in the sizes of the left and right kidneys, kidneys in boys and girls, or kidneys in various days of life were detected. To compare renal size of the newborns with other anthropometric parameters, renal volume should be correlated to body surface size. The data on renal size in healthy newborns may be used as reference values for newborns of the first week of life. PMID- 1755488 TI - [Present-day possibilities and prospects of development of ultrasonic diagnosis in perinatology and gynecology]. PMID- 1755489 TI - [Evaluation of fetal protective-adaptive reactions in gestosis and pelvic presentation]. AB - Biophysical profile of the fetus (BPF) was determined with the use of ultrasonic scanning and cardiotocography in 21 pregnant women with the pelvic presentation of the fetus and 32 patients with gestosis. Uteroplacental and fetoplacental circulation were also under study. The results of studies were analyzed together with the data on the labor outcome and course of the neonatal period. The findings evidence a regular depression of some BPF elements in hypoxia. Circulatory disorders in gestosis are initiated by disorders of the uteroplacental circulation, followed by involvement of the fetoplacental circulation in this process. Reduced BPF parameters in pelvic presentation of the fetus evidence functional immaturity of the fetus. A close relationship between the results of BPF assessment and fetal Doppler ultrasonics data has been revealed. PMID- 1755490 TI - [Ultrasonic diagnosis of intrauterine fetal infection in pregnancy of a high-risk group]. AB - Ultrasonic scanning of 315 pregnant patients with infectious inflammatory diseases and 200 healthy pregnant women has demonstrated the echographic markers of intrauterine fetal infection: hydramnios, the presence of meconium in amniotic fluid, untimely maturation and signs of infectious involvement of the fetus, increased size of fetal abdomen as against the reference values after 35 weeks gestation. Twenty-six of the 37 mothers of the newborns with pyoseptic diseases had presented with at least three of these signs. Ultrasonic scanning is recommended for antenatal diagnosis of intrauterine infection as an objective method. PMID- 1755491 TI - [Data on renal hemodynamics in uncomplicated pregnancy based on Doppler ultrasonography]. AB - The authors analyze the results of Doppler scanning studies of renal and intrarenal hemodynamics carried out in 69 women with normal pregnancy of 6 to 41 weeks and 8 healthy nonpregnant women, examined during the first phase of the cycle. Specific features of renal hemodynamics over the course of normal pregnancy were analyzed, as was the relationship of these hemodynamic changes and the status of the mother-placenta-fetus system. The authors come to a conclusion that Doppler scanning holds good promise for studies of the renal and intrarenal blood flow. PMID- 1755492 TI - [Echographic and morphological parallels in the evaluation of the condition of the uterine scar]. AB - Examinations of 86 women included echography, examination of the lower segment of the uterus during surgery, control manual examination of the postpartum uterus, and histologic examination of the tissues collected from the so-called cicatrix site. The authors claim that the criteria of the myometrial adequacy are the V shaped lower segment of the uterus, at least 3-4 mm thick, continuous anterior contour of the uterus, the presence of a homogenous echostructure or a structure with small sites of elevated echogenicity. A balloon-shaped lower segment of the uterus and its thinness (less than 3 mm), no continuity in the uterine contour, predominance of elevated echogenicity incorporations in the echostructure of the cicatrix site indicate the inadequacy of the myometrium at the site of the transverse cicatrix in the lower segment of the uterus. The findings evidence that echography is a highly informative method for the diagnosis of the uterine cicatrix status and that echographic examinations should be widely used to choose the delivery mode for pregnant women with a history of abdominal delivery. PMID- 1755493 TI - [Use of echography in the management of labor in women with uterine scar after cesarean section]. AB - Successful management of 26 normal deliveries has demonstrated a high diagnostic value of ultrasonic examination of the cicatrix on the uterus before, during, and immediately after delivery. Employment of this method to choose the strategy of labor management helped reduce the number of vaginal examinations in a number of cases and do without control manual examinations of the postpartum uterine cavity. PMID- 1755494 TI - [Characteristics of the fetoplacental blood flow in labor]. AB - Ultrasonic Doppler scanning was used to study the fetoplacental blood flow before labor, at the height of pang (uterine contraction), and 5-15 seconds following it. 53 parturients were examined during the active phase of labor. They were divided into two groups with different blood flow parameters. The findings evidence a deterioration of umbilical arterial blood flow after a uterine contraction is over, as against its level at the peak of labor pang. These results may be used to assess fetal status, because cyclic changes in the blood flow in umbilical arteries are particularly manifest in deterioration of the fetal status. PMID- 1755495 TI - [Cerebral blood flow in healthy newborn infants in the early neonatal period]. AB - Dynamic Doppler scanning studies of brain blood flow were carried out in 78 healthy newborns in the first days of their lives. The measurements were carried out in the internal carotid, basilar , anterior, median, and posterior cerebral arteries at the age of 30 min, 2 h, 1, 2, 3, and 4 days. Vascular resistance of brain vessels was assessed and the resistance index estimated. This index was found to increase by the second hour of life (p less than 0.001) in the anterior, median, and internal carotid arteries, whereas no noticeable changes in this index value were recorded in the basilar and posterior cerebral arteries. The resistance index reduced in all the examined arteries starting from the end of the first day of life. Parallel with these studies, arterial pressure was measured in all the examinees by the oscillographic method, and found reduced by the second hour of life. This permitted a conclusion on the reduction of the brain blood flow by the second hour of life and its elevation starting from the second day of life. Pulsed Dopplerography method is noninvasive, highly informative, and holds good promise for studies of the brain blood flow in the newborns. PMID- 1755496 TI - [The role of echography in the complex dynamic examination of patients with retardation of sexual development]. AB - Seventy-nine patients with sexual development retardation were examined, 24 of these suffered from ovarian genesis condition and 55 from central genesis condition. The findings evidence that detection of the uterus and gonads presenting as cords is one of the diagnostic criteria indicating gonadal dysgenesis. Echographic examinations carried out over the course of therapy yield a more accurate picture of ovarian function. No increase in uterine size on the echogram after discontinuation of hormonal therapy and the appearance of follicles in the ovaries after treatment point to normally functioning ovaries and helps specify the origin of sexual development retardation. In sexual development retardation of a central origin ultrasonic scanning helps assess the therapy efficacy and predict its outcome. PMID- 1755497 TI - [First experience with magnetic resonance tomography in the diagnosis of gynecologic pathology]. PMID- 1755498 TI - [Experience in the complex evaluation of fetal condition during pregnancy]. PMID- 1755499 TI - [Ultrasonic diagnosis during the treatment of patients with cancer of the uterine body]. AB - Transabdominal ultrasonic scanning was used to examine 48 patients with endometrial carcinoma; 39 of them were later operated on, and 5 of these examined in various periods after surgery. No image of the median uterine echo in women with clinical symptoms of cancer of the body of the uterus or thinning of the median structure may evidence in favor of poorly-differentiated adenocarcinoma. The authors emphasize the usefulness of echography in the diagnosis of the depth of the tumor invasion into the myometrium, detection of the recurrences, and pay special attention to imaging the uterine myoma and other associated diseases of the genitals in these patients. PMID- 1755500 TI - [Prenatal cytogenetic diagnosis using chromosomal preparations of the native biopsy samples of chorionic villi, cultured chorionic cells and amniocytes]. AB - Analysis of the results of prenatal cytogenetic diagnosis carried out in the first and second pregnancy trimesters in more than 300 women permitted comparing the efficacies of two methodologic approaches, diagnostic amniocentesis and chorion sampling , with due consideration for the methodologic errors typical of these methods and of the tested biologic material. Up to 5% of the diagnoses are erroneous if the diagnosis is based on chorion sampling data, whereas in amniocentesis the share of diagnostic errors is lower by an order. The authors have given a theoretical rationale for and tried a methodologic approach, involving the employment of the 'direct' chromosomal preparations from villous chorion biopsy specimens and the so-called 'maintained' cell culture technique, that permits obtaining chromosomal preparations of higher quality and, consequently, helps improve the accuracy of chromosomal diagnosis. PMID- 1755501 TI - [Transvaginal echography in clinical practice]. PMID- 1755502 TI - [Critical state of the fetoplacental blood flow: diagnosis, outcome and obstetrical tactics]. PMID- 1755503 TI - Addiction as a public health problem. PMID- 1755504 TI - Polymorphism of the rat liver mitochondrial aldehyde dehydrogenase cDNA. AB - In humans, a deficiency in mitochondrial aldehyde dehydrogenase (Class 2 ALDH) activity due to a single base-pair exchange in its structural gene serves as a deterrent to excessive alcohol consumption. Differences in Class 2 ALDH isozyme patterns on isoelectric focusing gels have been observed in the selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats. To determine whether the differences are the result of sequence variation in the structural gene, we sequenced the cDNAs for Class 2 ALDH from P and NP rats. A synonymous exchange was seen in the codon for amino acid 473 in both lines, when compared with published sequences. Additionally, when the cDNA from P rats was used as reference, a substitution (G for A) was identified in the cDNA of NP rats which changes amino acid 67 from Gln (CAG codon; ALDH2Q allele) to Arg (CGG codon; ALDH2R allele). The Arg for Gln substitution makes the enzyme more basic and could account for the different electrophoretic mobilities. To determine whether the polymorphism was associated with drinking behavior, we genotyped the ALDH2 locus by amplifying rat genomic DNA encompassing the nucleotide exchange followed by probing with allele-specific oligonucleotides. There are highly significant differences in the frequencies of the two alleles in the P and NP rat lines. The frequency of the ALDH2R allele is 63% in the NP line and only 18% in the P line, whereas the frequency of the ALDH2Q allele is 82% in the P line and 37% in the NP line. PMID- 1755505 TI - Chronic alcoholism impedes the recovery of renal function following renal ischemia. AB - The recovery of renal function following renal ischemia was studied using rats fed for 1-, 3-, and 5-week periods with an alcoholic diet (ethanol provided 36% of total calories). Renal ischemia was produced by clamping the renal artery and vein for 20 min. Renal function was determined 24 hr after the ischemia. In the absence of ischemic insult, the renal function of rats fed with an alcoholic diet for 1, 3, and 5 weeks was not significantly different from those of nonalcoholic rats. In nonalcoholic rats, renal function (24 hr postischemia) were: glomerular filtration rate (GFR) 430.4 +/- 29.6 microliters/min/g KW (kidney weight), renal plasma flow rate (RPFR) 1.4 +/- 0.17 ml/min/g KW, and fractional sodium excretion (FENa) 2.0 +/- 0.04% (mean +/- SE). Postischemic renal function of rats on 1- and 3-week alcoholic diets were essentially the same as that of the control rats. However, the 24-hr postischemic renal function of 5-week alcoholic diet rats was significantly depressed. The values were only 117.2 +/- 35.2 microliters/min/g KW (p less than 0.05) for GFR, 0.31 +/- 0.12 ml/min/g KW (p less than 0.05) for RPFR, and 7.46 +/- 3.59% for FENa. The present results demonstrate that the rat kidney subjected to prolonged alcohol ingestion was more susceptible to renal insult than a nonalcoholic kidney. PMID- 1755506 TI - Cerebral blood flow and metabolic rate in the conscious, freely moving rat: the effects of hypercapnia, and acute ethanol administration. AB - We propose a simple method that can be used to measure cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral glucose consumption (CMRglu) in the conscious, freely moving rat. The method is based on the classical Kety Schmidt approach, and uses a chronic cannula in the confluens sinuum. We tested the method by investigating the response of CBF, CMRO2, and CMRglu to hypercapnia and used the approach to investigate the effects of acute alcohol administration. Severe hypercapnia (PaCO2 approximately 80 mmHg) increased the CBF by a factor of 3.5, decreased the CMRO2 by 30%, and had no significant effect on the CMRglu. Under normocapnic conditions moderate blood alcohol levels (100-200 mg%) caused no significant effects on CBF, CMRO2, or CMRglu, but high blood alcohol levels (250-400 mg%) decreased all three parameters by approximately 25%. Under hypercapnic conditions high blood alcohol levels had no effect on CBF, CMRO2, and CMRglu. PMID- 1755507 TI - Effect of chronic ethanol feeding on hepatic and extrahepatic distribution of vitamin E in rats. AB - The effect of chronic ethanol feeding on the status of alpha- and gamma tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat. PMID- 1755508 TI - Ethanol fails to modify [3H]GR65630 binding to 5-HT3 receptors in NCB-20 cells and in rat cerebral membranes. AB - Low concentrations of ethanol have been found to enhance the electrophysiologic effect of serotonin (5-HT) acting at 5-HT3 receptors on NCB-20 cells. To determine whether this action of ethanol reflects a change in the agonist receptor interaction, the effect of ethanol (100 mM) on agonist and antagonist binding to 5-HT3 receptor was studied in vitro in membrane from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [3H]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [3H]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [3H]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [3H]GR65630 binding by 5-HT was approximately 30%. Ethanol decreased the affinity of the receptor for 2-methyl-5-HT, but not to 5-HT in NCB-20 cells, and had no effect on agonist binding in brain membranes. The results indicate that enhancement of 5-HT responses at 5-HT3 receptors by ethanol is not a result of changes in the equilibrium binding characteristics of the agonist. PMID- 1755509 TI - Ethanol-induced enhancement of cocaine bioactivation and irreversible protein binding: evidence against a role of cytochrome P-450IIE1. AB - Chronic ethanol consumption potentiates cocaine-induced liver injury in rodents. Since cocaine has to be bioactivated by a cytochrome P-450-dependent N-oxidative pathway to exert its hepatotoxic effects, we studied the role of the ethanol inducible P-450IIE1 for cocaine metabolism. Male Sprague-Dawley rats were pretreated with either a liquid diet containing ethanol (30% of calories) for 4 weeks or injected with pyrazole (200 mg/kg/day, ip, for 3 days). Both agents induced microsomal p-nitrophenol hydroxylation which is a probe for the catalytic activity of P-450IIE1. However, only ethanol, but not pyrazole, increased both microsomal cocaine N-demethylase activity (by 47%) and the extent of irreversible binding of [3H]-cocaine to microsomal proteins (by 100%), which was taken as a quantitative endpoint for the formation of a reactive metabolite. Cocaine N demethylation and irreversible protein binding of cocaine were not inhibited by P 450IIE1 isozyme-selective substrates, nor was the rate of cocaine metabolism and binding decreased by functionally active polyclonal anti-rat P-450IIE1 antibodies. Furthermore, pyrazole pretreatment sensitized cultured hepatocytes to the glutathione-dependent cytotoxic effects of nontoxic concentrations of cocaine. These results indicate that (a) cocaine is not a major substrate for the ethanol-inducible P-450IIE1, (b) the enhancing effects of ethanol on cocaine bioactivation may be due to induction of other P-450 isoforms, and (c) induction of P-450IIE1 may potentiate cocaine-induced hepatocellular toxicity in vitro independently of cocaine metabolism, e.g., by P-450IIE1-dependent oxidative stress. PMID- 1755510 TI - Increased ventricular vulnerability in a chronic ethanol model despite reduced electrophysiologic responses to catecholamines. AB - An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755511 TI - Flow cytometric and immunohistochemical evaluation of ethanol-induced changes in splenic and thymic lymphoid cell populations. AB - Ethanol-induced alterations in the immune system are thought to play a major role in increasing the susceptibility of alcoholics to infections and tumors. One important change in the immune system is the noted loss of lymphoid cells from the thymus and spleen. To examine these alterations we used a model system where C57Bl/6 mice were pair-fed either a Leiber-DeCarli diet containing 7% (v/v) ethanol or an isocaloric control diet. Mice receiving ETOH for 7 days showed a loss of cells from the spleen and thymus; this loss was even more severe after withdrawal for 1 day. The most profound changes were seen after 2 weeks of ETOH. Spleen and thymus cell numbers were reduced to 36% and 6.2%, respectively compared to control mice. Staining of thymocytes with monoclonal antibodies to lymphocyte surface markers and evaluation with flow cytometry revealed that immature thymocytes (PNA+, CD4+/CD8+) were most reduced. Mature thymocytes (CD4+/CD8- or CD4-/CD8+) were depleted, and the CD4+ to CD8+ ratio was increased. Sections of thymus stained with hematoxylin and eosin or with immunohistochemical methods showed atrophy and lymphoid cell depletion. No cortex was histologically identifiable after 2 weeks of ETOH. The spleen cells most affected by ETOH were the B cells. They were reduced to 8.2 x 10(6) cells/spleen (31.5% of the lymphocytes), as compared to 38.5 x 10(6) cells/spleen (50.3% of the lymphocytes) in the control mice. The spleen was atrophic, but the immunoarchitecture was preserved. Ethanol causes a depletion of lymphocytes from the spleen and thymus with alterations in lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755512 TI - Multi-enzyme catalyzed rapid ethanol lowering in vitro. AB - Ethanol was oxidized to acetate by an enzyme system using yeast alcohol dehydrogenase (YADH), yeast aldehyde dehydrogenase (YALDH), and lactic dehydrogenase (LDH) recycling NAD in two model duodenal fluids and in canine duodenal aspirate in vitro. Sufficient enzyme activities were maintained to convert as much as 34% of the original ethanol to acetate with negligible acetaldehyde accumulation. PMID- 1755513 TI - Chronic ethanol-induced impairments in receptor-mediated endocytosis of insulin in rat hepatocytes. AB - The effects of chronic ethanol administration on the receptor-mediated endocytosis of insulin were investigated in isolated hepatocytes. When hepatocytes were isolated from rats that were fed an ethanol liquid diet for 5-6 weeks, these cells bound 25% less insulin to their surface membrane than did cells from the chow-fed or pair-fed controls. This decreased binding was likely a result of reduced surface receptor number rather than changes in receptor affinity. Rates of insulin degradation were also reduced by 25-30% in hepatocytes from the ethanol-fed animals. In addition, chronic ethanol feeding induced a defect in the internalization of the receptor-insulin complex and altered the hepatocellular processing of the internalized insulin. These results indicate that chronic ethanol administration impairs both the surface binding and the endocytosis of insulin by the liver. PMID- 1755514 TI - Isoelectric focusing/western blotting: a novel and practical method for quantitation of carbohydrate-deficient transferrin in alcoholics. AB - Carbohydrate-deficient transferrin (CDT) has been described as the single, most accurate marker of chronic alcohol consumption. Rapid, sensitive, and specific measurement of serum CDT levels can thus provide important clinical information concerning patient diagnosis and treatment. To date, however, methods used for assessing CDT concentrations [e.g., analytical isoelectric focusing combined with immunofixation and micro anion-exchange chromatography followed by radioimmunoassay (RIA)] have not been practical enough for widespread laboratory application. In the present study, we examined the use of a different technique, namely isoelectric focusing (IEF) combined with Western blotting (IEF/WB). Serum proteins (20-40 micrograms) were first focused according to isoelectric points (pI) on high-resolution agarose IEF gels (ampholyte pH range of 5-8) containing nonionic detergent. The focused proteins were transferred electrophoretically to nitrocellulose filters, and then stained immunochemically with antihuman transferrin IgG. IEF/WB completely resolved CDT (focusing at pI 5.7 and 5.9) from other serum transferring isoforms, as assessed with neuraminidase-generated CDT standards. Computerized densitometric scanning of the immunoblots allowed CDT levels to be quantitated directly rather than as a quotient. Serum CDT content determined by IEF/WB was highly correlated (r2 = 0.962; n = 17) with values determined previously by RIA. In a larger subject group, CDT levels (mg/liter) measured by IEF/WB were 139 +/- 54 in recently-drinking alcoholics (n = 58), 81 +/- 8 in abstaining alcoholics (n = 7), and 68 +/- 16 in healthy control subjects (n = 16).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755515 TI - The phytoestrogens present in de-ethanolized bourbon are biologically active: a preliminary study in a postmenopausal woman. AB - Bourbon and some other alcoholic beverages have been shown to contain phytoestrogens which, as a result of an excessive intake and alcohol associated liver disease, have been suggested as contributing to the feminization of chronic alcoholic men. To evaluate this hypothesis directly, de-ethanolized bourbon was prepared and orally administered to a single postmenopausal woman. Serum or plasma levels of luteinizing hormone, follicle stimulating hormone, sex steroid binding globulin, high density lipoprotein cholesterol, and estradiol were monitored before, during, and after administration of the de-ethanolized bourbon at a dose equivalent to 4 ounces of bourbon for 20 days. The changes observed for each parameter during the injection of the bourbon extract are consistent with the presence of a biologically active estrogenic substance being present in the bourbon extract. These observations provide the first direct evidence in man for the presence of a biologically active estrogenic substance(s) in bourbon. PMID- 1755516 TI - Development of tolerance to and physical dependence on ethanol: daily versus repeated cycles treatment with ethanol. AB - We examined the effect of various treatment schedules with ethanol on the development of tolerance and the severity of withdrawal in rats. Tolerance to ethanol was examined after a challenge dose of ethanol using rectal temperature, dowel performance, and tail flick response; open field activity and the startle response were determined during withdrawal. Animals treated daily with ethanol developed greater tolerance, and also lost it faster, compared with animals subjected to repeated cycles of 3 days of ethanol treatment followed by 3 drug free days. Also, the severity of withdrawal was greater in animals treated daily with ethanol. In the second study, we examined the development of tolerance and withdrawal severity of animals subjected to three different schedules of daily ethanol administration. Overall, the animals receiving continuous infusion of ethanol showed the most severe withdrawal and had, except for dowel performance, the fastest loss of tolerance to ethanol. PMID- 1755517 TI - The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. AB - There is a growing body of evidence indicating that chronic alcohol consumption induces morphological changes in the central nervous system (CNS) similar to those observed during brain senescence, including an increased formation of lipofuscin. In addition, it was also found that alcohol withdrawal does not reverse these changes. On the contrary, most of the alterations observed during alcohol consumption worsen as happens with the increased lipofuscin formation. Thus, using our model of alcohol feeding and withdrawal, we decided to examine the effects of different drugs said to offer neuronal protection during CNS degenerative processes. The action of piracetam, a cyclic derivate of GABA and commonly used as a nootropic agent, was tested by studying the lipofuscin accumulation on the cerebellar Purkinje and hippocampal CA3 pyramidal cells in alcohol-treated and withdrawn rats. Piracetam was found to markedly decrease the formation of neuronal lipofuscin. Whatever the functional implications of this pigment, its reduction in piracetam-treated animals might be related either to a protective effect on the intraneuronal membranous system or to an antioxidant property of this molecule. PMID- 1755518 TI - Event-related potentials in alcoholic men: P3 amplitude reflects family history but not alcohol consumption. AB - Multilead event-related potentials (ERPs), elicited by auditory and visual stimuli requiring a button press response and by a startling noise requiring no response, were recorded from male alcoholics and age-matched male controls (26-60 years old). Single-trial analyses of blink responses to the startling stimuli indicated that alcoholics startle less frequently but with equivalent amplitude as the controls. In contrast, single-trial analyses of P3 indicated that alcoholics generate a P3 as often as controls, but that their individual P3s are smaller. Alcoholics who reported a positive family history of problem drinking had larger startle blink amplitudes and smaller auditory and visual P3s than did alcoholics who reported a negative family history. Hierarchical regression analysis was used to demonstrate that smaller P3s in family history positive alcoholics were independent of lifetime alcohol consumption. PMID- 1755519 TI - Applications of Cloninger's subtypes in a female alcoholic sample. AB - This study examined the incidence of Type 1/Type 2 symptoms and age of alcoholism onset in a population of alcoholic women in order to determine whether there were females similar to the Type 1 and Type 2 male alcoholics described by Cloninger and colleagues. Using a sample of 51 alcoholics divided into early and late alcoholism onset groups (less than 25 and greater than or equal to 25), the early onset group did not manifest merely Type 2 symptomatology nor did the late onset group manifest Type 1 symptoms without the occurrence of Type 2 symptoms, as would have been predicted by the Cloninger theory. Rather, the majority of women endorsed both types of symptoms regardless of their age of alcoholism onset, making classification by sympton type unsuccessful. However, combining symptoms across types (making a total of 7) produced 71% classification of subjects into early symptom onset (ESO) and late symptom onset (LSO) groups. Analyses indicated differences between the groups in each of five areas: (1) demographic and psychosocial variables, (2) alcohol abuse severity, (3) family history, (4) psychopathological symptoms, and (5) substance abuse history. In each case the ESO alcoholics resembled the characteristics of male Type 2 alcoholics reported in other studies. The findings indicate that modification of the Cloninger classification criteria to reflect age of symptom onset regardless of symptom "type" provides better classification of individual female alcoholics and suggests that female alcoholics are represented in both Type 1 and Type 2 alcoholic subtypes. PMID- 1755520 TI - EEG characteristics in males at risk for alcoholism. AB - Baseline EEG activity was recorded with eyes closed in 15 males, aged 19 to 24 at risk (HR = high risk) for the development of alcoholism and 15 matched controls (LR = low risk). Four EEG frequency bands were examined: slow alpha (7.5-10 Hz), fast alpha (10.25-12.75 Hz), slow beta (13-19.5 Hz) and fast beta (19.75-26 Hz). The HR and LR groups were compared on four measures of EEG activity for each frequency band: band power, absolute and relative area and laterality differences. Statistical analysis of the data via ANOVA revealed no significant difference between the HR and LR groups for any comparison. The results indicate that EEG measures prior to alcohol administration do not effectively discriminate between individuals at high and low risk for alcoholism. PMID- 1755521 TI - Six- and twelve-month abstinence rates in inpatient alcoholics treated with aversion therapy compared with matched inpatients from a treatment registry. AB - Two hundred forty-nine patients who were treated for alcoholism in an inpatient multimodal treatment program that included aversion therapy were matched post hoc on 17 baseline variables with patients from a national treatment outcome registry. The latter patients received inpatient treatment that emphasized individual and group counseling as the primary therapeutic elements but did not include aversion therapy for alcohol. Six- and 12-month abstinence rates from alcohol and all mood-altering chemicals are reported. The patients treated with aversion therapy for alcohol had higher alcohol abstinence rates at 6 and 12 months (p less than 0.01). The abstinence rates from all mood-altering chemicals were higher in the aversion group at 6 months (p less than 0.05) but not at 12 months. The largest differences between treatment groups in 6-month alcohol abstinence rates were noted for males (p less than 0.001), those over 35 (p less than 0.001), daily drinkers (p less than 0.001), and those with alcohol-related work performance problems (p less than 0.05). PMID- 1755522 TI - Macrocytosis as a consequence of alcohol abuse among patients in general practice. AB - Macrocytosis, a common finding in patients without anemia or other hematologic abnormalities, is often ignored. The purpose of this prospective study was to investigate 300 consecutive, adult health-center patients with a mean cell volume (MCV) value greater than or equal to 100 fl. The incidence of macrocytosis was 2.4%. Of the 177 male and 123 female patients, only 14 (4.7%) were anemic; 80.2% of the men (89.3% of those under 60 years) and 34.1% of the women were alcohol abusers, representing the largest diagnostic group. The highest MCV value found in alcoholics without folate or vitamin B12 deficiency was 120 fl. The most useful laboratory test for identifying alcohol abuse among macrocytic patients was the measurement of serum gamma-glutamyltransferase. Of the several morphologic abnormalities in the marrow the only specific finding were vacuoles in the granulocyte or erythrocyte precursors. No underlying cause was found for macrocytosis in 6.8% of the men and 35.8% of the women. Even when it is not associated with anemia, macrocytosis should not be ignored. It may be the only indicator of a disease which often, particularly in young and middle-aged men, is alcohol abuse. PMID- 1755523 TI - Urinary markers of chronic excessive ethanol consumption. AB - A gas chromatographic mass spectrometric procedure is described for the measurement of free ethanol and conjugates of ethanol and acetaldehyde. It was demonstrated that conjugates of ethanol and acetaldehyde were present in urine of alcoholics. Urinary levels of free ethanol and the conjugates in abstaining alcoholics were higher than those of social drinkers. On the average, alcoholics excreted equal amounts of free ethanol and ethanol conjugates while controls eliminated three parts of ethanol conjugates to one part of free ethanol. After 14 days of abstinence, 16/23 (70%) of alcoholics had levels of free ethanol and acetaldehyde conjugates higher than the mean +2 SD of social drinkers for these substances. When the molar ratio of ethanol conjugates/free ethanol was considered, five more subjects who were alcoholics could be classified as being alcoholics. There was one false positive among 46 control subjects. PMID- 1755524 TI - Aggressive and nonaggressive behavior as a function of alcohol intoxication and frustration in women. AB - An experiment tested whether alcohol increases aggression in women in a situation in which both an aggressive and a nonaggressive response alternative of equal instrumentality and of equal variability are available. Subjects were assigned to one of three groups, namely, an alcohol, a placebo, or a control group. The alcohol dose was 1.0 ml of pure alcohol/kg body weight. After drinking their respective drink, subjects were instructed to supervise a bogus partner on a visual scan test over a series of trials. Each time this partner made a mistake, subjects could either give an uncomfortable electric shock (scale 1 to 10) or a comfortable vibration (scale 1 to 10) to the partner. Aggressive and nonaggressive behavior was measured as numbers, intensities, and durations of shocks or vibrations, respectively. Neither alcohol nor frustration differentiated the groups on aggressive or nonaggressive behavior. All groups were significantly more inclined to use the nonaggressive alternative irrespective of alcohol dose and level of frustration. In conclusion it was stated that women do not increase their aggression as a function of alcohol in a situation with more than one response alternative available. The need to incorporate gender differences as to aggressive effects of alcohol was stressed. PMID- 1755525 TI - Psychiatric comorbidity in alcoholism: importance of ascertainment source. AB - Although psychiatric comorbidity is often observed among individuals in treatment facilities for alcoholism, the prevalence and pattern of psychiatric comorbidity among alcoholic cirrhotics has not been well characterized. The present study aimed first to compare the prevalence of psychiatric comorbidity in cirrhotic individuals with alcoholism ascertained from a gastroenterology service with alcoholics ascertained from a treatment facility for alcoholism. Consistent with the findings of other investigators, the data suggest that there is a great degree of variability regarding the severity of alcoholism in alcoholic cirrhotic individuals. Furthermore, cirrhotics with alcoholism exhibited a less severe clinical picture of alcoholism as measured by less alcohol dependence and lower prevalence of psychiatric comorbidity than individuals in treatment for alcoholism. The main conclusion of this study is that ascertainment source is an important determinant of psychiatric comorbidity observed in alcoholic samples. PMID- 1755526 TI - Noncirrhotic liver dysfunction and neuropsychologic impairment. PMID- 1755527 TI - Tetrahydropapaveroline and alcohol preference. PMID- 1755528 TI - [Conscious and unconscious acoustic perception during general anesthesia]. AB - The possibility of processing sensory information during general anesthesia and the ability to recall it postoperatively is of major ethical, medical and even theoretical importance. Auditory stimuli especially are perceived intraoperatively and remembered postoperatively. Neuropsychological experiments indicate that sensory information can be processed and recalled both at a conscious and at an unconscious level. Therefore, we have to distinguish between explicit and implicit memory. Explicit memory is characterized by an active and conscious recall of space- and time-related events, i.e., episodes in a person's life. In contrast, implicit memory recalls passively and unconsciously without being related to space and time, i.e., language and general knowledge. Experimental results from amnesic patients indicate that these two memory systems work independently from each other. Even when explicit memory is grossly impaired the function of the implicit memory may still be completely preserved. Various studies on intraoperative awareness show that explicit memory is widely eliminated during general anesthesia. The incidence of conscious awareness that can be actively recalled postoperatively is reported to be 1-3%. In contrast, the implicit memory function can be partially preserved. When implicit memory tasks or hypnosis are employed, traces of unconscious memory of intraoperative auditory information can be shown in 20-30% of the patients. These observations are of important clinical relevance, because the unconsciously recalled information about the intraoperative procedure may have a negative influence on the patient's postoperative recovery and well-being. So far it is still not known which anesthetics most reliably suppress auditory perception and conscious and unconscious memory during the intraoperative period. Therefore, future studies should focus on several different points. The anesthetic state should be defined exactly and the functional state of the auditory modality should be monitored when auditory information is presented to the patients. The recollection of intraoperative events should be investigated using implicit memory tests, because these are regarded as more sensitive than explicit memory tests. PMID- 1755529 TI - [The importance of autologous blood transfusion in the Federal Republic of Germany. Results of a survey carried out in 1989]. AB - The study was designed to evaluate the role of autologous blood transfusion in current clinical practice. METHODS. Standardized questionnaires were distributed to the anesthesia departments of 421 randomly selected hospitals in the 'old' Federal Republic of Germany and West Berlin in August 1989. The questionnaires contained 26 questions relating to (1) the particular hospital, (2) preoperative autologous blood donation (PABD), (3) preoperative plasmapheresis, (4) isovolemic hemodilution, (5) intra- and postoperative autotransfusion, (6) general practice followed in blood transfusion, and (7) blood salvage in children. RESULTS. In all, 207 completed questionnaires (49%) were returned, 12% of which came from university hospitals, 25% from hospitals with more than 500 beds, 58% from hospitals with fewer than 500 beds and 5% from smaller specialized hospitals. Over half (52%) of the responding hospitals were running their own transfusion services or were located in the vicinity of a regional blood bank. The overall proportion of surgical procedures requiring perioperative blood transfusions was 10%. PABD was performed "not at all" in 24% of the hospitals, "rarely" in 28%, "occasionally" in 24%, "frequently" in 10%, and "routinely" in 13%. PABD was standard in 75% of the departments of orthopedic surgery, in 68% of the departments of cardiac surgery, and in 33% of the departments of vascular surgery. In two-thirds of the hospitals reporting the use of PABD, the anesthesia departments were in charge of the autologous blood service. For 64% of the hospitals, liquid storage of whole blood was reported as the standard technique. Patients normally not eligible for homologous blood donation according to established donor criteria were accepted for autologous blood donation at most "occasionally" in 60% of the hospitals, but "frequently" or "mostly" in 36%. Preoperative autologous plasmapheresis was performed when major intraoperative blood loss was anticipated in 12% of the hospitals. Isovolemic hemodilution was performed "not at all" in 30% of the hospitals, "rarely" in 17%, "occasionally" in 25%, "frequently" in 14%, and "mostly" in 12%. The reasons most frequently given for not performing hemodilution were "too time-consuming" (41%) and "too little blood-saving effect" (32%). Autotransfusion devices were available in 40% of the hospitals. Others deemed such devices "badly needed" (5%) or "desirable" (43%), while 45% found them "not necessary." The principal use of intraoperative autotransfusion was in cardiac surgery (79% of the departments), orthopedics (47% of the departments) and vascular surgery (45% of the departments). In 29% of the responding hospitals autotransfusion devices were also used for postoperative autotransfusion ("seldom" in 7%, "occasionally" in 10%, "frequently" in 6%, "mostly" in 6%). In the absence of cardiopulmonary disease, hemoglobin concentrations below 8-10 g/dl were considered an indication for blood transfusion. In patients with compromised cardiopulmonary function the lowest acceptable level was 10-12 g/dl. Blood salvage techniques are obviously rarely used in children. Experiences with PABD in children were reported by 14.5% of the hospitals, experience with isovolemic hemodilution by 22% and with intra- and postoperative autotransfusion in 18% and 12.5% of the hospitals, respectively. Preoperative plasmapheresis was performed in children in 3.5% of the hospitals. CONCLUSIONS. Although the present sample is not representative on a national level, our findings allow the conclusion that the simple techniques of both preoperative autologous blood donation and isovolemic hemodilution are unduly neglected in surgical and anesthetic practice, whereas even smaller hospitals are fairly well equipped with sophisticated autotransfusion devices. PMID- 1755530 TI - [Intra-arterial catheter oximetry and pulse oximetry in comparison with CO oximetry in heart surgery]. AB - This study evaluates the measurement of oxygen saturation by arterial catheter oximetry and pulse oximetry. The values are compared to values obtained by CO oximetry. METHODS. In eight patients undergoing cardiac surgery, we determined the oxygen saturation of arterial and mixed-venous blood by CO-oximetry (IL 282, Instrumentation Lab) at prospectively defined points of measurement before, during, and after extracorporeal circulation. At the same points of measurement, saturation readings obtained by arterial catheter oximetry (U425C, Abbott) and pulse oximetry (Siemens/Nellcor) were recorded. RESULTS. The mean saturation values determined by both catheter oximetry and pulse oximetry differed from the mean values obtained by CO-oximetry by less than 1% (= bias). The standard deviations of the readings in relation to readings of CO-oximetry (= precision) were +/- 0.5% to +/- 1.0% for catheter oximetry and +/- 1.0% to +/- 1.3% for pulse oximetry. Furthermore, it was possible to obtain saturation readings in 99% 100% of measurements by catheter oximetry; in contrast, this was possible by pulse oximetry in only 59%-84% of measurements. Low mixed-venous saturation values were not indicated by any of the arterial methods of measurement. CONCLUSIONS. Catheter oximetry was superior to pulse oximetry with regard to both precision of saturation values and reliability to obtain values. Invasiveness and high costs are disadvantages of catheter oximetry, but if reliable and exact measurements are important at any time during surgery or intensive therapy, intra arterial catheter oximetry is preferable to pulse oximetry. PMID- 1755531 TI - [The effect of combination epidural anesthesia techniques in upper abdominal surgery on the stress reaction, pain control and respiratory mechanics]. AB - Twenty-eight patients undergoing upper abdominal operations (mainly selective proximal vagotomy [SPV]) were referred for assessment of the hormonal metabolic reaction (adrenocorticotropic hormone [ACTH], arginine vasopressin [AVP], cortisol, and glucose), the postoperative pain reaction, and respiration according to the method of anesthesia (group 1: neuroleptanesthesia [NLA], group 2: NLA in combination with epidural opiate analgesia, group 3: NLA in combination with local anesthesia). To alleviate postoperative pain piritramide was systematically administered in group 1, whereas in groups 2 and 3 a thoracic epidural catheter was injected with morphine or bupivacaine. Postoperative analgesia was better in patients with epidural administration than in those with systemic application. On the 1st and 2nd postoperative days the vital capacity was statistically significantly higher by 10%-15% in groups 2 and 3 than in group 1. As expected, the neurohormonal and metabolic stress response was highest in all patients in the intraoperative and immediate postoperative phases: ACTH, AVP, and glucose levels were in most cases significantly higher compared with the initial values. However, cortisol levels decreased intraoperatively, probably as a result of the generally used induction agent etomidate. Comparison of the three methods of anesthesia revealed that all mean hormone levels analyzed in group 2 patients were lower both intraoperatively and 2 h postoperatively, which implies that epidurally administered morphine reduces the stress reaction, probably indirectly through additional selective alleviation of pain at the spinal cord level. The various differences in hormonal reactions of patients in groups 1 and 3 gave no clear evidence, however, of possible mitigation of the stress reaction by epidural local anesthetics in upper abdominal operations. PMID- 1755532 TI - [Patient-controlled analgesia versus epidural analgesia using bupivacaine or morphine following major abdominal surgery. No difference in postoperative morbidity]. AB - In 1987, Yeager et al. reported that intraoperative epidural anesthesia with local anesthetics and postoperative epidural analgesia with opiates diminished postoperative morbidity. In our first clinical trial on this topic, the better postoperative analgesia with epidural bupivacaine-fentanyl failed to improve the outcome after major abdominal operations over that obtained with parenteral piritramide. This randomized controlled investigation was designed to assess whether intraoperative epidural anesthesia with bupivacaine plus light general anesthesia and postoperative epidural analgesia with morphine would diminish the overall rate of postoperative complications after major abdominal operations compared with general anesthesia (without epidural) followed by patient controlled analgesia with morphine, and with intraoperative epidural anesthesia with bupivacaine and light general anesthesia followed by postoperative bupivacaine-morphine analgesia. METHODS. A total of 292 patients undergoing infrarenal aortic bypass operation, gastric resection, gastrectomy, duodenum preserving pancreatic resection, Whipple's operation or cystectomy and neobladder formation were randomly divided into three groups: 1. PCA group (patient controlled analgesia, n = 107): patients were operated on under general anesthesia (midazolam, fentanyl, N2O/O2, if necessary with addition of halothane, enflurane or isoflurane; muscle relaxation with pancuronium bromide). Postoperative management consisted in patient-controlled analgesia with morphine (Prominject), bolus 2 mg, lock-out 5 min (recovery room, intensive care unit) or 15 min (surgical ward). 2. EBM group (epidural bupivacaine+morphine, n = 95): operation under light general anesthesia (midazolam, low-dose fentanyl, N2O/O2, pancuronium bromide). In addition, a mixture of bupivacaine (0.25%) and morphine (60 micrograms/ml) was infused (approximately 0.1 ml/kg.h) via an epidural catheter during and after the operation (approximately 72 h). 3. EM group (epidural morphine, n = 90): operation under the same kind of general-epidural anesthesia as in the EBM group. Postoperatively, epidural injection of morphine (0.05 mg/kg in 10 ml of saline) on request up to the 3rd postoperative day. Quality of analgesia (at rest and when patients coughed vigorously), strength of cough, and rate-pressure product were recorded at 8:00 h, 12:00 noon, 16:00 h and 20:00 h on the 1st, 2nd and 3rd postoperative days. Incidence and intensity of all postoperative complications (cardiovascular, pulmonary, renal and other organ failure, reoperations, major infection, sepsis, thromboembolism, metabolic and mental disturbances) were assessed from the day of operation until discharge or death (n = 10), respectively. RESULTS AND DISCUSSION. In the PCA and EM groups analgesia was equal but of slightly inferior quality compared with the EBM group. The ability to cough was best in the EBM group and significantly worse in the PCA and EM groups, with no difference between the last two. (ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1755533 TI - [Mechanical ventilation in an anesthetic circle system using the lowest tidal volume--studies of 3 anesthesia ventilators in a lung model and an animal experiment]. AB - No anesthesia ventilator attached to a circle system is manufactured for use in neonates. However, a small bellows can be supplied for the following anesthesia ventilators: Spiromat NS 656 (NS), Ventilog 2 (V2) and AV1 (Draeger Co.) We investigated the minimal tidal volume delivered by each of the three ventilators. In addition, we tested the performance of the AV1 in neonatal piglets for manual and controlled ventilation, and in decreased lung compliance. MATERIALS AND METHODS. All circuits were equipped with one CO2 canister (750 ml) and the low compliance tubes of the "Ulmer Kinder Set" (Ruesch Co.) The circuits were connected to a lung model consisting of a glass cylinder filled with copper wool with a compliance of 3.0 ml/mbar. By using calibrated glass syringes we created a pressure-volume correlation for the entire system, i.e., the lung model, the anesthesia circuit and the ventilator, which was linear for each of the three ventilators. The pressure was measured in the test lung. The pressure increase caused by the tidal volume therefore reflected the actual tidal volume delivered, which was calculated using the pressure-volume correlation. Tidal volumes were determined for varying the fresh gas flow (FGF), the respiratory rate (RR), which was varied between 20 and 60/min and the I:E ratio (IE), which was varied between 1:1 and 1:2. Six newborn piglets aged 2-12 h and with body weight 1000-1300 g were anesthetized, tracheotomized and ventilated with an oxygen-nitrous oxide mixture (FIO2 0.25). The manual ventilation lasted 30 min (period 1) and was followed by mechanical ventilation for 60 min (period 2). Thereafter, a left pneumothorax with constant pressure of 20 mbar and then 40 mbar for 15 min each was created (period 3). A fall in blood pressure was treated with 10 ml colloids in five of the six animals. During the experiment arterial blood pressure in the carotid artery, mean airway pressure at the distal end of the tracheal tube and end-tidal CO2 were continuously recorded. Arterial blood gases were analyzed at the end of each period. RESULTS. The tidal volumes delivered with an identical position of the bellows varied in ventilators NS and V2 with changes in FGF, RR and IE. Decrease in FGF, higher RR and longer expiration resulted in a decrease in the tidal volume. The "smallest" tidal volume delivered by NS varied from 50 ml (FGF 2 l/min, RR 60, IE 1:2) to 188 ml (FGF 4 l/min, RR 20, IE 1:1) and from 11 ml (FGF 2 l/min, RR 60, IE 1:2) to 110 (FGF 4 l/min, RR 20, IE 1:1) in the V2. The AV1 showed a minimal tidal volume of about 5 ml, and no changes in tidal volume attributable to alterations in FGF, RR or IE could be observed. No problems occurred during manual or mechanical ventilation in the piglets. With the experimental decrease in lung compliance no increase in airway pressure was noted, but an increase in arterial pCO2 by 8 mmHg (mean) reflects hypoventilation that was not corrected by the ventilator. DISCUSSION. We believe that the changes in tidal volume in ventilators NS and V2 are caused by adding FGF to the volume delivered by the below during inspiration. Because of the unpredictability of the tidal volumes, these ventilators are not suitable for the use in neonates. The AV1 has a very low systemic compliance which makes it suitable for use in neonatal anesthesia. However, a decrease in lung compliance is not compensated by an increase in airway pressure and leads to hypoventilation. When small tidal volumes are used in patients with low lung compliance, it does not act as expected of a volume-cycled ventilator. PMID- 1755534 TI - [Anesthetic gas contamination in the operating room--an unsolved problem? Results of our own studies]. AB - Ambient air concentrations of nitrous oxide (N2O) and volatile anesthetics were assessed under routine conditions in a total of 41 surgical suites located at seven Vienna hospitals. Continuous measurements were performed by means of infrared trace gas analyzers throughout a period of approximately 450 h. Additional analyses of ventilation facilities (if installed) revealed no essential deficiencies; however, anesthetic gas scavenging (AGS) systems yielded insufficient flow rates in 32% (less than 25 l/min). In surgical suites without mechanical ventilation or scavenging systems (2 out of 41), maximum occupational threshold limits (i.e., 100 ppm N2O; 5 ppm halothane) were exceeded continuously and to considerable degrees throughout the duration of anesthesia. During measurements conducted in operating rooms (ORs) in otolaryngology departments, extreme peaks (greater than 2600 ppm N2O, greater than 150 ppm halothane) of several minutes duration were documented when open-circuit anesthesia was performed. In the general surgical ORs equipped with modern ventilation facilities ambient air contamination was lowest, time-weighted average (TWA) values ranging from 8 to 15 ppm (mean 11 +/- 3 ppm) for N2O and 0.1 to 0.6 ppm (mean 0.3 +/- 0.2 ppm) for the halogenated anesthetic. Despite good ventilation and scavenging in the gynecological ORs, distinctly higher concentrations (mean 83 +/- 49, range 24-211 ppm N2O; mean 0.75 +/- 0.3, range 0.3 to 1.3 ppm volatile agent) were measured in cases where anesthesia was delivered by mask. TWA values exceeding currently established maximum workplace concentrations were found in an unscavenged but ventilated urological OR. At present, short-term concentration peaks seem to be inevitable even under optimal OR ventilation conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755535 TI - [A case of serum cholinesterase anenzymia]. AB - A report is given on a 66-year-old man suffering from serum cholinesterase anenzymia. The following tests were performed to characterize the genetic pseudo cholinesterase variants: plasma cholinesterase activity using benzoyldicholine as substrate (according to Kalow) and dibucaine and sodium fluoride as inhibiting substances. In addition, polyacrylamide density gradient gel electrophoresis followed by esterase staining technique (Mascall) was used for the electrophoretic separation of cholinesterase isoenzymes. Similarly, the only daughter's and the granddaughter's sera were analyzed. Determination of activity and inhibitor numbers indicated that the propositus had the homozygote "silent gene" genotype (A = 2, DN = 0, FN = 0). The granddaughter showed an isoenzyme constellation within normal ranges (A = 128, DN = 80, FN = 58); for the daughter apparently normal values were also found for activity and inhibitor numbers (A = 73, DN = 82, FN = 58). Figure 1 shows the results of electrophoretic separation from the sera tested and Fig. 2 results obtained by densitometric assessment. Electrophoretic separation and the zymogram obtained from the propositus' serum show only sample peak and albumin fractions. In contrast, the granddaughter's serum turned out to be absolutely normal. In the daughter's sample, however, three cholinesterase components normally found in serum were missing, as also shown by densitometry. Despite apparently normal activity and rather insignificant inhibitor numbers, gradient gel electrophoresis clearly revealed her to be a heterozygote carrier of the silent gene Es variant. As our data are in accordance with results obtained by other investigators, this observation cannot be regarded as exceptional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755536 TI - [Orthotopic liver transplantation following heart transplantation]. AB - Heart transplantation was performed in a 24-year-old man suffering from dilated cardiomyopathy who was also infected with hepatitis B virus and had not yet seroconverted. Most likely due to the immunosuppression, the hepatitis exacerbated and soon led to hepatic dystrophy and precoma. In this phase of congruent rejection of the heart transplant, liver transplantation was performed. During the procedure the patient had stable circulatory parameters and a reduced cardiac output. The heart rate and cardiac output stabilized after release of the anastomosis of the hepatic vessels. The patient survived for 6 months and died at home with signs of a myocardial infarction. PMID- 1755537 TI - [Mean equipotent blood pressure-lowering concentrations of halothane, isoflurane and enflurane during balanced anesthesia differ from conventional MAC-values]. AB - Balanced anesthesia is a technique that allows control of blood pressure in patients with coronary artery disease. In order to evaluate the relative requirements of volatile anesthetics during basic opioid analgesia, 51 patients with unimpaired left ventricular function who were undergoing coronary artery bypass grafting during balanced anesthesia were investigated. They were randomly assigned to three groups, i.e. halothane (H), isoflurane (I), and enflurane (E). Permanent medications were maintained up to 12 h preoperatively. After premedication with flunitrazepam, promethazine and piritramide, anesthesia was induced with 7 micrograms/kg fentanyl, 0.3 mg/kg etomidate, and 0.1 mg/kg pancuronium and continued with fentanyl infusion (0.1 microgram/kg-1 min-1). Volatile anesthetics were applied in oxygen/air and adjusted to keep the mean arterial blood pressure within +/- 20% of the preoperative value. End-expiratory concentrations of volatile anesthetics were measured (Capnomac, DATEX) and averaged over time. The mean ages of the patients in the different groups were 60 +/- 7.6 years (H), 59 +/- 7.1 years (I), and 60 +/- 6.9 years (E). Four patients in the halothane group, six in the isoflurane group, and five in the enflurane group took beta-blockers preoperatively. The cumulative doses of fentanyl were: H = 0.80 +/- 0.17 mg, I = 0.85 +/- 0.16 mg, and E = 0.83 +/- 0.16 mg at the time of skin incision and H = 1.20 +/- 0.26 mg, I = 1.38 +/- 0.19 mg, and E = 1.24 +/- 0.25 mg at the beginning of extracorporeal circulation.2+ which are possibly the reason for the high O2-MAC value, which may be abolished during balanced anesthesia. However, both the negative inotropic and the vasodilatory effects of enflurane are more likely explanations for the results. It is concluded that 0.5 to 1.0 MAC of halothane, isoflurane, or enflurane used as equipotent components of balanced anesthesia for blood pressure control during aorto-coronary bypass grafting may differ considerably from the conventional MAC concept. PMID- 1755538 TI - [Pseudoaneurysms of the radial artery following iatrogenic punctures. Comments apropos 2 cases]. PMID- 1755539 TI - [Thoracic sympathectomy in the surgical treatment of Raynaud's phenomenon]. AB - Authors present their results from a review of 38 thoracic sympathectomies practiced since 1977 to 1987, both included, on patients affected by a Raynaud syndrome resistant to medical treatment. Results show the evident clinical improvement of such patients after surgery. In all cases, surgical approach was a Crafoord thoracotomy. PMID- 1755540 TI - [Vascular injuries of the lower extremity]. AB - Authors present their experience (32 patients affected by a traumatic femoropopliteal injury) with vascular traumatisms at the lower limb. Causes, treatment and successful results with the new technics and the early clinical management to the patients are commented. PMID- 1755541 TI - [Reinterventions in late failures of femorodistal grafts]. AB - In this retrospective study of 195 patients treated for late failure of a previous femoral-distal reconstruction, there were 178 men and 17 women ranging in age from 42 to 79 years. The graft material utilised for initial operation was an autoenous vein (reversed saphenous vein (75), in situ (1) and arm veins (4) in 80, polytetrafluoroethylene in 51, Dacron in 46, Biografts in 12 and composite grafts in 6 patients. The previous site for distal anastomosis was above the knee in 70 and tibial or peroneal arteries in 18 cases. The most common cause of graft failure was late thrombosis (95), progression of the underlying disease (64), deterioration of the graft (15), pseudoaneurysms (8), and rerelly perigraft reactions, hemodynamic insufficiency, late infection, etc. The aim of the reoperation was: graft extension for distal disease (68) desobstruction and patch angioplasty (21), thrombectomy (9) exchange of the graft (17), local repair of the graft (3). Seventeen patients required inflow procedures. Other reinterventions (sympathectomy, catheterisation and prostaglandin perfusion, were used in patients with no chance for reconstructive arterial surgery. Secondary reoperations were performed in 12, tertiary operations in 7 patients. Major amputations rate, operation mortality, wound morbidity and hemodynamic success rates with limb salvage in reoperated patients support usefulness of repeated revascularisation when femoro-distal bypass failure occurs. PMID- 1755542 TI - [The Granada-90 geriatric angiological study (1)]. AB - Because the high incidence of cardiovascular disease between aged people and because the problematic features of Andalusian community, like its vast extension, high percentage of people older than 65 years, low sociocultural level and lack of physicians specialized on Angiology; an important study was made in order to analyze such type of disorders as well as their factors of risk. Study was made transversally with 443 hospitalized aged patients. PMID- 1755543 TI - [Selective renal hypothermia in the surgical treatment of juxtarenal aortic aneurysms]. PMID- 1755544 TI - [Antibiotic treatment in patients amputated for ischemic diabetic foot]. AB - Thirty diabetic patients submitted to a major amputation were tested by humo celullar assays (retarded hypersensibility assays). Reactive patients were subdivided into two groups: one group was treated postoperatively with antibiotics, and the other group was not treated. Both groups were homogeneous in age, hemoglobin concentrations, hematocrit, total proteins, glucemy and history of sepsis or leukocytosis. Five patients treated with antibiotics (33.3%) presented sepsis, one patient was reamputated and one patient died. Between the not treated patients, only three presented sepsis (20%) without any other complications. Authors conclude that the development of sepsis in reactive, diabetic, amputated patients is independent of antibiotic treatment. PMID- 1755545 TI - [Postoperative spinal cord ischemia in thoracoabdominal aneurysms]. AB - At the present article, 12 cases of paraplegia secondary to the surgical treatment of thoracoabdominal aneurysms are presented. Study includes patients admitted between 1973-1987 for treatment and rehabilitation of its medular injury. Factors of risk, surgical technics practiced, peroperative complications and type of medular injury are analyzed. The most common medular injury was an anterior medular syndrome (rather than 60%). In the same way, preventive methods are analyzed and somatosensory evoked potentials (SEP) and motor evoked potentials (MEP), both in developing phase at the present moment, are recommended as the most viable method for detecting changes during the surgical procedure. PMID- 1755546 TI - Pandemonium over gloves: use and abuse. PMID- 1755547 TI - A study of the use of gloves in a large teaching hospital. AB - A study was conducted in the wards and laboratory of a 900-bed teaching hospital to determine the appropriateness of glove use. In the wards the rate of appropriate use was 59%, and in the laboratory it was 90%. In general, in the patient areas gloves were used for specific tasks (70%) whereas in the laboratory use for a specific task was only 32%. Financial savings could be realized by educational programs in infection control directed toward a more rational use of gloves. PMID- 1755548 TI - Health care facilities in a rural state: an examination of infection control policies. PMID- 1755549 TI - Recommendations for urinary catheter and drainage bag changes. PMID- 1755550 TI - [Discount on anesthetic safety]. PMID- 1755551 TI - [Controlled trial of a non-invasive continuous blood pressure monitor: Cortronic AMP 770]. AB - The performances of a Cortronic AMP 770 monitor, a new apparatus for non invasive continuous blood pressure monitoring was assessed. Its working principle is derived from oscillometry. The blood pressure cuff is kept at a low pressure (about 20 mmHg), and the oscillations induced by the arterial pulse are converted into blood pressure. Systolic, mean and diastolic blood pressure was measured in 9 healthy volunteers, under physiological conditions, using both the AMP 770 and a traditional oscillometer (Physiogard SM 785 NI, Odam). A group of 124 paired measurements was obtained, with values ranging from 87 to 150 mmHg for systolic pressure, from 48 to 97 mmHg for diastolic pressure, and from 63 to 114 mmHg for mean pressure. The mean differences (APM 770-Physiogard) were -1.2 +/- 10 mmHg for systolic pressure, 3.2 +/- 8 mmHg for diastolic pressure, and -3.8 +/- 8 mmHg for mean pressure. There was no correlation between blood pressure levels and discrepancy in the measurements obtained with the two methods. The Cortronic AMP 770 was reliable under normal circumstances, when compared with a traditional oscillometer. However further studies are required to assess its reliability under pathological circumstances (severe hypotension or hypertension, arrhythmias and sudden changes in blood pressure). PMID- 1755552 TI - [Comparative value of clinical signs of difficult tracheal intubation in women]. AB - A prospective study was designed to compare the value of clinical signs aimed to predict difficult intubation in women. A group of 663 women, scheduled for elective surgery, were assessed by an anaesthetist at the preanaesthetic visit. Following parameters were assessed: the degree of mouth opening, the chin-hyoid bone and the chin-thyroid cartilage distances, dental and facial abnormalities, age, weight. All patients were ranked on the Mallampati scale. Another anaesthetist carried out the anaesthetic induction and endotracheal intubation. The latter was deemed to have been difficult if special procedures had been required (use of a stylet, a fibroscope, or Sellick's manoeuvre). In accordance with these criteria 12.5% of women were difficult to intubate. Furthermore, he assessed the degree of glottic exposure, using a Macintosh blade and according to Cormack's classification. Six per cent of women were ranked C or D in Cormack's classification (C: the glottic aperture was not seen; D: the epiglottis was not seen). Finally 66% of women with difficult intubation and 84% of those with severely abnormal glottic exposure were ranked greater than 1 on the Mallampati scale. This scale had high sensitivity (0.84), but a specificity of only 0.66. Other clinical criteria (mouth opening, the chin-hyoid bone distance) had a lower sensitivities, but seemed more specific. Multivariate analysis showed that specificity could be improved (0.84) if the distance between the upper and lower incisor teeth (mouth opening) was associated with Mallampati's rank, without any loss in sensitivity. A simple chart is proposed to assess the risk of difficult intubation. PMID- 1755553 TI - [Incidence and etiology of cardiac arrest occurring during the peroperative period and in the recovery room. Apropos of 102,468 anesthesia cases]. AB - This study reviewed retrospectively 186 cardiac arrests (CA) observed in a series of 102,468 anaesthetics, carried out in a University Hospital between 1983 and 1987. Among them 29 were partly or totally related to anaesthesia and 11 had a fatal outcome. On the other hand, 157 CA (144 deaths) were not related to anaesthesia. Mortality rate due to anaesthesia was therefore 1.1 per 10,000. The main causes of anaesthesia related CA were overdosage, with or without hypovolaemia (9 CA, 6 of which occurred under regional anaesthesia); hypoxaemia (6 CA, 5 of which occurred under regional anaesthesia) and multifactorial sudden cardiac arrest (n = 8). The other aetiologies were: myocardial ischaemia (n = 3); anaphylactic shock due to propanidid (n = 1); protamine accident (n = 1); ventricular arrhythmia due to hypokalemia (n = 1). Fourteen CA occurred during induction (2 deaths), 14 during maintenance (8 deaths), and one during recovery. Risk factors for CA included a high ASA class, and the type of anaesthesia: there were 8 CA for 12,981 regional anaesthetics, and 21 for 89,487 general anaesthetics (p = 0.017). Emergency and paediatric anaesthesia were not risk factors. Outcome was independent of ASA class, but was related to aetiology: hypoxaemia (5 out of 6 recovered) and overdose with or without hypovolaemia (7 out of 8 recovered) had favourable outcomes. Furthermore, outcome of CA due to regional anaesthesia was satisfactory (7/8 recovered) (p = 0.08, NS). Such an analysis of the causes of anaesthetic disasters and their rate of occurrence can lead to more effective prevention. PMID- 1755554 TI - [Pharmacokinetics of continuous infusion of etomidate in cirrhotic patients]. AB - The pharmacokinetics of etomidate were studied in 9 control subjects (with normal liver function) and in 5 patients with cirrhosis scheduled for gastro-intestinal surgery. Anaesthetic induction included an initial bolus of etomidate 0.3 mg.kg 1, together with fentanyl 2 micrograms.kg-1, and pancuronium 60 micrograms.kg-1. An etomidate infusion was then started according to one of two following schemes: a (0.03 mg.kg-1.min-1 for 10 min, and then 0.01 mg.kg-1.min-1), or B (0.1 mg.kg 1.min-1 for 10 min, followed by 0.02 mg.kg-1.min-1 for a further 110 min, and 0.01 mg.kg-1.min-1 thereafter). Plasma concentrations of etomidate were determined at regular intervals throughout anaesthesia, and up to four hours afterwards, using inverse phase high pressure liquid chromatography. The infusion was given for 273 +/- 87 min in controls, and for 259 +/- 56 min in the cirrhotic group. Scheme A, only used in 3 controls and 1 cirrhotic in a preliminary study, resulted in very low plasma concentrations: 0.2 to 0.4 micrograms.ml-1. Those measured during the apparent plateau phase (steady state) of infusion protocol B were close to predicted values (0.5 to 0.6 micrograms.ml-1) in controls, whereas higher concentrations (approximately 1.5 micrograms.ml-1) were reached in cirrhotic patients. For all the patients the time interval to spontaneous recovery was 41 +/- 27 min; plasma levels were then 0.199 +/- 0.092 micrograms.ml 1. There were significant alterations in pharmacokinetic parameters in the cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755555 TI - [Sedation with intranasal midazolam for endoscopy of the upper digestive tract]. AB - Twenty-nine patients, ranked ASA 1 or 2, scheduled for diagnostic gastroduodenal fibroscopy were randomly allocated into three treatment groups: intranasal midazolam (IN) 0.15 mg.kg-1; intramuscular midazolam (IM) 0.15 mg.kg-1, and placebo (P). Sedation and the fibroscopy were all carried out by the same anaesthetist and fibroscopist. Efficiency and tolerance of the method were assessed by monitoring the heart rate, systolic and diastolic arterial blood pressure, arterial oxygen saturation (pulse oximetry), the degrees of sedation, anxiety, and anterograde as well as retrograde amnesia. The patient's and endoscopist's reactions were also considered. Patients in group P were older than those of the other two groups (p less than 0.01). Sedation was more important and patients less anxious in groups IN and IM than in group P. Three patients in group IM had retrograde amnesia. There were no significant differences between the degrees of anterograde amnesia in the three groups. At no time during the study were there any significant differences in SpO2 between and within groups. Four out of the 9 patients in group P had a bad opinion of their experience, as compared with two out of the 20 in the midazolam groups; the difference was not statistically significant. Three hours after the procedure, all patients were fully awake. Intranasal administration of midazolam therefore seemed to be an interesting alternative for gastroduodenal fibroscopy, because it was simple, non traumatic, well tolerated, and did not result in arterial desaturation. PMID- 1755556 TI - [Cerebral aspergillosis in immunocompromised patients]. AB - Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported. All three had neurological symptoms with normal cerebrospinal fluid (CSF). The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium. They also had pulmonary signs and fever despite antibiotic treatment. Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid. Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine. Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit. Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney. The CT scan signs were quite different from those seen with the more usual bacterial ring lesions. In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis. Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis. Early antifungal treatment is the only chance of survival. Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise. PMID- 1755557 TI - [Paraplegia after epidural anesthesia for vascular surgery]. AB - A case is reported of a 67-year-old man who underwent major vascular surgery (iliobifemoral bypass with unilateral sympathectomy) under epidural anaesthesia and resulting in permanent neurological damage. Lumbar epidural anaesthesia was carried out using a mixture of bupivacaine, lidocaine with adrenaline, and alfentanil. The surgical course was uneventful, except for a 30 minute period of relative hypotension (90 vs. 110 mmHg preoperatively). Continuous epidural analgesia (12 ml.h-1 of 0.125% bupivacaine without adrenaline) was started after the end of surgery. Twelve hours later, flaccid lower limb paralysis was noted, but thought to be due to the bupivacaine. At the 24th hour, the epidural analgesia was discontinued and the catheter removed. There were a motor paralysis and a partial sensory block, raising to the level of T10 (temperature and pain). A CT scan and myelography of the thoracolumbar spine revealed no anomaly. The sensory loss ended within ten days, but the motor deficit regressed only slightly. Unfortunately, the patient died on the 16th day after an episode of severe chest pain. The probable cause of the neurological damage was an anterior spinal infarct. It was not possible to determine the degree of responsibility of the peripheral vascular disease, the anaesthetic or the surgery. PMID- 1755558 TI - [Pseudosurgical acute abdomen syndrome in primary pulmonary hypertension]. AB - The case is reported of a 49-year-old chronic alcoholic woman, who presented with severe pulmonary arterial hypertension (PAH) mimicking as an acute abdomen. She was admitted with right-sided hypochondrial abdominal pain and hepatomegaly, with a moderate jaundice. On admission to intensive care unit, she had an arterial blood pressure of 110/70 mmHg, a heart rate of 100 b.min-1, and a respiratory rate of 36 c.min-1. An electrocardiogram showed sinus rhythm and right-sided heart failure. Whilst breathing 6 l.min-1 oxygen, her arterial blood gases were: PaO2 47 mmHg PaCO2 29 mmHg. Severe PAH was confirmed by measuring her mean pulmonary arterial pressure, which was 46 mmHg, whilst her pulmonary wedge pressure was 7 mmHg. Hepatic function was also altered: total bilirubin 41 mumol.l-1, alkaline phosphatase 145 UI.l-1 and gamma glutamyl transferase 1 340 UI.l-1. She developed arterial hypotension, which did not respond to increasing doses of isoproterenol. She died on the third day. Necropsy confirmed the diagnosis of primary PAH, with acute "cardiac liver". PMID- 1755559 TI - [Contact dermatitis caused by a peripheral intravenous catheter with metallic connector]. AB - A case is reported of a 26-year-old woman who developed contact dermatitis due to a peripheral venous catheter. This catheter had a metal connector, made of nickel brass. The patient had been admitted for uterine contractions and was to receive an infusion of salbutamol. Twelve hours after the catheter had been set up, she developed at the puncture site an acute inflammatory reaction, with oedema and bullae. She later admitted to having had a few "spots" when wearing a cheap metal bracelet. Skin tests with nickel (5% solution of nickel sulphate) confirmed the diagnosis. This case underlines the importance of looking for an allergic history in patients. PMID- 1755560 TI - [Post-traumatic constrictive pericarditis with fast course]. AB - A case is reported of a 46-year-old male patient who sustained a blunt thoracic injury with an anterior flail chest, and right haemopneumothorax. He was intubated and ventilated because of acute respiratory failure. There were initially no signs suggesting any myocardial injury. It was not before day 20 that the electrocardiogram showed a QS wave in leads V2 and V3. The hypothesis of an antero-septal myocardial infarct was not confirmed by echocardiography, which only revealed slight thickening of the posterior pericardium. From day 50 on, the patient had tachycardia, raised jugular venous pressure, and effort dyspnoea. Echocardiography (day 59) showed an anterior and posterior pericardial effusion (about 500 ml), marked pericardial thickening, and inferior vena caval collapse during inspiration, with normal myocardial wall movements. Drainage pericardiocentesis was therefore carried out, followed by, four days later, a pericardiectomy. A small ecchymosis was found on the anterior aspect of the right ventricle. The pericardium was thickened, fibrous, hyperhaemic, Case is y stuck to the epicardium. Eight months later, echocardiography showed that the posterior pericardium remained thickened, and there was a very small residual effusion. Movements of the septum had returned to normal. PMID- 1755561 TI - [Coma during transurethral resection of the prostate]. AB - Two cases of coma occurring during transurethral resection of the prostate are reported. The 76 and 85-year-old patients lapsed into coma, ranking 9 and 8 on the Glasgow scale, respectively 90 and 120 min after the start of the resection, without any previous haemodynamic alterations. In one patient, coma occurred when the urethral catheter became blocked with fragments of prostates. In the other, coma was initiated by a rupture of the prostatic capsule, with passage of washing fluid (1.5% glycine solution) into the peritoneal cavity. The role played by acute hyponatraemia (128 and 123 mmol.l-1 respectively) and glycine poisoning (10,188 and 11,840 mmol.l-1 respectively) are discussed. These cases underline the interest of regional anaesthetic techniques, allowing an early diagnosis and a rapid surgical procedure which will avoid a worsening of the condition. PMID- 1755562 TI - [Xenon, inhalation anesthetic: a comeback?]. PMID- 1755563 TI - [Asystole during anesthesia with propofol]. PMID- 1755564 TI - [Lyell's syndrome and griseofulvin]. PMID- 1755565 TI - [Laryngeal mask for the reduction of nose fractures]. PMID- 1755566 TI - [Laryngeal mask for bronchoscopy in children]. PMID- 1755567 TI - [3rd Consensus Conference on anti-infectious therapy. Osteoarticular bacterial infections except mycobacterium infections (Tours, January 25, 1991)]. PMID- 1755568 TI - Drug prescription monitoring systems in general practice. PMID- 1755569 TI - VIDEOFAR: an epidemiologic tool for drug utilization studies. AB - VIDEOFAR is a computerized drug prescription monitoring system oriented to gain an epidemiological insight into the phenomenon of "drug prescription". The set of activities carried out within the VIDEOFAR project were focused to: define methods of analysis of prescription data, which could be transferred to the peripherical operating settings of the National Health Service (Local Health Units, Epidemiologic Observatories, Regional Pharmaceutical Services, etc.); implement a Drug Data Base to allow a flexible utilization of information; implement software systems in different computer environments. PMID- 1755570 TI - The logical structure of the VIDEOFAR drug data base. AB - The quality of the analyses that can be carried out by a Drug Prescription Monitoring System depends on the completeness and accuracy of the information on drugs. Data quality depends also on the organization of the data base that must be designed to allow higher retrieval power with regard to the information level theoretically contained in stored data. Considering these requirements we developed inside the VIDEOFAR project, starting from the preceding experiences at the Istituto Superiore di Sanita, an activity of design and realization of a Drug Data Base whose structure, both logical and physical, is described. PMID- 1755571 TI - Drug utilization studies within the VIDEOFAR project. AB - The epidemiological use of drug prescription data is getting increasing attention in Italy. All Italian citizens are included in the National Health Service (NHS) which reimburses almost every drug prescription. The potential information content of such systems have to be evaluated within a technological context which will allow, for medium term, drug prescription data collection for all of the individuals served by the NHS. The VIDEOFAR project did explore the possible use of drug prescription data for descriptive epidemiological studies, in the evaluation of General Practitioners activity and as a tool for Post-Marketing Drug Surveillance. Some examples are presented in this paper using data derived from Latium Region. PMID- 1755572 TI - Possible applications of drug prescription monitoring systems in Italy. AB - Numerous experiences have already been implemented as regards the use of data concerning drug prescriptions and relative expenditure. This article focuses firstly on how such data are used from an administrative point of view in the Veneto Region, and secondly on the cultural and scientific aspects involved. The supply of feedback to general practitioners (GPs) with drug prescription indicators has made possible to cut down farmaceutical expenditure. Moreover, the analysis of the substances used by the GPs highlights the areas which require special attention in order to improve the quality of prescription. PMID- 1755573 TI - Information systems for the analysis of drug prescriptions in Spain. AB - The Spanish National Health Service, largely represented by INSALUD, covers at present over 98% of the Spanish population. Services are free at the point of delivery with exception of prescription charges. The patients contribution towards the price of their medicines is approximately 40% of the cost of the drug for most ethical preparations. Non-prescription drugs are not reimbursed by the National Health Service. Pensioners and the disabled are exempt from prescription charges. Prescription analysis or monitoring is possible within INSALUD because of the necessity to reimburse pharmacists for the prescriptions they dispense, monthly batches of prescriptions are processed. The Drug Data Bank possesses three databases that may be used for prescription analysis, these are ESPES, ECOM and PACTIV. Information from these databases is used by external workers in: drug Monitoring Centres for Adverse Drug Reactions; the Spanish Collaborative Study on drug-induced birth effects; drug utilization research workers; INSALUD also produces reports on drug prescribing and these have a particular emphasis on expenditure; the General Directorate of Pharmacy also use these databases for their policy making on issues related to, and derived from prescribing. PMID- 1755574 TI - Drug utilization studies and drug monitoring in The Netherlands. AB - Drug utilization research is a research area of increasing importance, as well in the Netherlands as elsewhere. In this article on overview is given of the situation in the Netherlands. Three types of studies are distinguished, descriptive studies, studies of the determinants of drug use and studies of the impact of drug use. Descriptive studies are needed to understand the present situation and to detect problems. If these problems are to be solved it is important to understand the factors that determine drug use. By looking what the impact is, the value of drug use for health care can be assessed. It is also an important tool for developing systems for drug monitoring at a patient level. At present community pharmacists play an important role in drug monitoring at the patient level. A problem still awaiting a solution is how to implement such systems effectively. PMID- 1755575 TI - Economic evaluation of drug prescription monitoring systems in the extra-hospital environment. AB - Drugs expenditure accounts for a significant and rising share of public health expenditure (from 14% in 1980 it has now reached 17% approximately). Many efforts have been made to contain its expansion through tickets (co-payments), formularies, price policies, etc., but overall results have been unsatisfactory. The main cause for this failure may be found in the approach adopted, virtually excluding the evaluation of rational use of drugs. Economic evaluation of drug prescription, comparing cost per DDD, assessing both cost/effectiveness ratios and the monitoring system's efficiency, may contribute to a better control of drug expenditure. PMID- 1755576 TI - Postmarketing surveillance and other epidemiologic uses of drug prescription data in the United States. AB - Currently the data resources available for conducting pharmacoepidemiology studies in the United States include spontaneous case reports of adverse reactions, aggregate population-based data resources, computerized collections of data from organized medical care programs, data collected for pharmacoepidemiolgy on an ongoing basis, existing data collected as part of other ad hoc studies, and data collected de novo for pharmacoepidemiology studies. The advantages and disadvantages of each and the particular contributions of drug prescription data to each approach are described. PMID- 1755578 TI - [Principles and application possibilities of cryoultramicrotomy]. AB - This paper reviews the technical aspects of cryoultramicrotomy. The key preparation steps in the technique, namely freezing, sectioning, thawing, and staining are analysed. The application of this method to immunocytochemistry and analytical electron microscopy are discussed with respect to the present possibilities and problems. PMID- 1755577 TI - Drug utilization studies and people. A Swedish perspective. AB - Innovative ways of collaboration between actors involved are needed to increase the quality of drug therapy. Sweden is fortunate to have access to reliable and detailed statistics on drug sales and prescribing patterns. The various data bases are being described. A common classification system (ATC) and a unit of measurement (DDD) enable comparisons at various levels. Major differences between countries, counties, and health centres are presented. Little is known about the reasons for these differences. In order to leave its infancy, drug utilization studies need that clinical pharmacology establishes linkages with primary health care where a majority of the prescribing takes place. Systems should also be developed activating the prescribers involving them in a revolving cycle of self audit. To study drug use in its context a multidisciplinary approach is needed. The descriptive phase should be complemented by targeted intervention and methods should be developed for drug information. Future drug utilization studies need more of a patient-prescriber perspective (PPP). PMID- 1755579 TI - Allergens and atopic diseases. AB - Allergens are molecules normally present in the environment, responsible of inducing the so called atopic diseases. These diseases are characterized by the high production of allergen-specific IgE antibodies, which bind to mast-cells and basophils. The cross-linking of the cell-bound IgE induces the production and/or release of various inflammatory mediators (histamine, leukotrienes, platelet activating-factor, etc.), which trigger a cascade of events resulting in the allergic syndromes. Once the diagnosis of allergy has been made, two different therapeutic approaches can be followed: a) the pharmacologic management, aimed mainly at preventing or controlling the symptoms resulting from the release of mediators by effector cells; b) the specific immunotherapy, consisting in the administration to the patient of increasing amount of the relevant allergens, opportunely prepared and eventually chemically modified. In order to have the latter approach correctly applied it is necessary to gain a wider knowledge on both regulation of IgE synthesis and allergens characteristics. PMID- 1755580 TI - Bracken as a risk factor in digestive tract tumors: state of the art. AB - The present knowledge of the risks of exposure to bracken fern (Pteridium aquilinum) is presented. The history of research on bracken toxicity is reviewed, covering the animal observations and chemical analysis, and focusing on the carcinogenic effects in various animal species and on the nature and biological properties of the known carcinogens. The implications of human exposure to bracken are inferred, the possible ways of contamination are discussed, and the existing epidemiological studies are commented. Bracken contribution to digestive tract tumors is deduced, and the need of further research on the plant toxicity and detailed epidemiological investigations with the exposed population is stressed. PMID- 1755581 TI - Day-time and night-time concentrations of airborne iron particles in the atmosphere of Madrid. AB - Specific measurements of iron aerosol have been made over a 70 days period at a semi-urban site of Madrid. Measurements were made with the idea of assessing the relative contributions of day-time and night-time concentrations to daily ones. Statistics of day-time, night-time, daily and survey time period concentrations are given. Time variations were studied as well, clearly showing daily cyclical pattern identified by applying time spectral analysis. This periodicity is undoubtedly due to level differences between day-time and night-time concentrations of aerosol. Day-time average level ranged from 0.23 to 5.13 micrograms/m3 over the entire survey period (70 days) in contrast with night times ones ranging from 0.17 to 3.04 micrograms/m3. Night-time/day-time concentration ratio shows a highly consistent value, 0.430 + 0.25 (sigma) during this period. On occasion when diffusion conditions are similar, this ratio increases to 0.518 + 0.18 (sigma). Day-time, night-time and daily concentrations correlation matrix suggests that former is the best daily level indicator. PMID- 1755582 TI - [10 years of legionellosis in Italy (June 1980-June 1990)]. AB - Legionella infection was recognized as a cause of human disease in 1976, following the occurrence of an epidemic at Bellevue Stratford Hotel, Philadelphia, USA. In the subsequent years, various cases, both sporadic and epidemical, have been reported worldwide. In Italy, the first reports date from 1980. The compulsory notification of the disease was established in February 1983, and a few months later a National Surveillance Programme started operating at the Istituto Superiore di Sanita, Rome. Up to June 30, 1990, 542 confirmed cases of legionellosis were reported. For 249 of them, data of clinical and epidemiological significance are available. The incidence of the disease is higher in males (76% of total cases) and 51.5% of the patients are aged more than 50 years. During the clinical course, the occurrence of hepatic and/or renal dysfunction, cough, dyspnoea, diarrhoea and confusion was documented in a significant proportion of patients. The fatality rate was 12.4%. The disease occurred both sporadically and epidemically. Namely, clusters and outbreaks were detected all over the country, accounting for a total of 97 cases. Hospital patients should be regarded as an important category at risk for infection. The occurrence is also frequent among travellers and tourists, because of the stressing factors that may increase individual susceptibility, as well as the more frequent contact with infective sources. In Italy, the major risk of infection appears connected with water plumbing systems of hotels, residential houses and hospitals, where oxygen bubble-humidifiers have been found to represent an important source of infection. On the contrary, the association of human infection with air conditioning systems has not been evidenced up-to-now. PMID- 1755583 TI - [Disability, perceived health, and risk of death in a cohort of elderly]. AB - An elderly cohort has been submitted to a five-year mortality follow-up in order to evaluate the relationship between environment, social and health conditions and survival probability. Particular attention has been directed to disability measure proposed by OECD (Organization for Economic Co-operation and Development). An extension of Cox multiple regression model has been used. Results show that the social and living conditions are not associated with survival probability. On the contrary, disability is a strong determinant of mortality risk and subjective health status is a modifier of its effect. Following disability level is an indicator of long-term health status and health services needs. PMID- 1755584 TI - [Examples of intervention in cases of electromagnetic pollution in research laboratories]. AB - Two examples of technical measures taken to reduce levels of radiofrequency electromagnetic radiation in research laboratories are reported. The first intervention was aimed at avoiding undue exposure of operators. The case is of interest because of the special exposure conditions, which are not as well characterized as in industrial applications, and require ad hoc analyses, measurements, and mitigation actions. As shown by the second example, such actions also allow effective screening of experimental apparatuses, which is of special importance when high sensitivities are required. PMID- 1755585 TI - [Congenital hypothyroidism: organization and coordination of neonatal screening in Italy]. AB - Congenital hypothyroidism (IC) is the most frequent endocrine disease of the infancy and it is caused by primary deficiency of thyroid hormones. The damages derived by protracted hormone deficiency are diffused to all organs and systems and particularly severe for the development of central nervous system. Mental retardation can be prevented by early diagnosis and therapy. Early diagnosis is assured by neonatal thyroid screening performed on all newborns in the first days of life. The progress report on the screening situation in Italy as well as the national coordination realized in this field are presented. PMID- 1755586 TI - [Epidemiologic surveillance of pleural mesothelioma in Italy]. AB - A collaborative study has been performed in order to detect cases of pleural mesothelioma diagnosed or treated in Italy in the years 1984-88. Cases have been notified to ISS by 88 centres (clinics of thoracic surgery and respiratory diseases, oncologic centres, institutes of pathology), active in 14 Italian regions. Altogether, 575 cases (415 males and 160 females) have been included in the study. Information on occupation and/or on non occupational exposure to asbestos was available for 65% of the subjects, and the occurrence of definite or possible exposure to asbestos was estimated for 58% of them. PMID- 1755587 TI - [Methods for the evaluation of a health intervention in developing countries: the case in the Arsi region, Ethiopia]. AB - Since 1989 an evaluation study of the impact of a Primary Health Care (PHC) program is being carried out in Arsi region, Ethiopia. The principal aim of the study is to estimate the mortality rates in those villages mainly involved in PHC activities. A sample of 80 villages will be recruited to allow significant differences in mortality of 20 per thousand between less treated and best treated villages. Considering the absence of routine demographic data, a population census and demographic surveillance of the recruited villages have been carried out. All the activities related to the study are considered together with the principal logistic and methodologic problems. PMID- 1755588 TI - [An experimental device for measuring the characteristics of echographic emissions]. AB - An experimental system for the evaluation of the parameters characterizing the acoustic power emission of echographs is described. The apparatus is based on a commercial device, which has been modified to allow the analysis of different echographic probes, particularly used for diagnosis. The modified instrument is quite versatile in use and is suitable for the examination of virtually any kind of probe. PMID- 1755589 TI - Outline of the ISS code for the classification of chemical substances for use in compiling a national inventory. AB - A coding system for categorizing all types of compounds was developed specifically as part of the National Inventory of Chemical Substances to be applied by the Istituto Superiore di Sanita (ISS) in order to comply with the EEC present legal provisions on chemicals in trade. A number of applications were also described to illustrate the coverage and the adaptability of the code. PMID- 1755590 TI - [Surgical trials in senology]. PMID- 1755592 TI - [Goiter recurrences after surgical resection]. AB - A personal experience about 135 pz. with non-toxic goitre treated by mono o bilateral thyroidectomy and followed during 5 years (2-8) to evaluate the incidence of recurrences is reported. The recurrences were 10.5%, especially after monolateral thyroidectomy (9 pz.). Therefore the authors stress the importance of a more accurate surgical indication, a wider resection of the gland and a careful follow-up to undertake opotherapy when hypofunction appears. PMID- 1755591 TI - [Intra- and postoperative changes in blood viscosity]. AB - Blood and plasma viscosity has been controlled in a group of patients undergone to aorto-iliac reconstruction and in a group of control after thyroidectomy, cholecystectomy, and hernioplasty. The hemodilution induced by intraoperative infusion in the vascular reconstruction produced an important decrease of hematic and plasmatic viscosity which lasted for several days after the operation. Removing the hemodilution effect by a mathematical correction of the viscosity measured values to a standard haematocrit, it has demonstrated as surgical operation, apart from its entity, promoted an increase of the viscosity which persisted long in the postoperative course. For what it concerns the risk of postoperative thrombosis from one side protective effect of hemodilution is confirmed, from the other, in absence of the hemodilution, it would be useful to continue the antithrombotic prophylaxis longer the perioperative time as usual. PMID- 1755593 TI - [The onset of local recurrences after radical therapy for rectosigmoid carcinoma]. AB - The authors after considering the natural history in 116 patients with rectosigmoid carcinoma examine a number of parameters and their significance in terms of predicting recurrence. Following curative surgery the authors conclude a particular significance is satisfying quality of life in patients with rectosigmoid carcinoma. PMID- 1755594 TI - [Pelvic recurrences after curative surgery for rectal cancer]. AB - This report updates an experience with local recurrences of rectal cancer after curative surgery. Overall 13 year period (1976-1988) 254 patients were operated on in the II Surgical Clinic of Parma University for rectal cancer. Only 122 patients who underwent potentially curative resection were examined. Approximate recurrence rates according to patients age, site, type and stage of primitive tumour, tumour complications and surgical procedures were evaluated. The overall local failure rate was 17.2% with 12 patients having local failure alone and 9 patients having concurrent local failure and distant metastasis. Local failure occurred predominantly in tumour bed, involving the anastomosis in 2 cases. Relapse developed primarily at colo-rectal anastomosis in only 1 patients, 20% of recurrences were diagnosed within the first postoperative year; 65% within the second and 90% within the third. Stage of primary tumour was the most predictive factor for eventual relapse. Minute foci of tumour not encompassed by the first operation led to local recurrences in most of the cases, but relapses were independent of operative procedures adopted. The authors conclude that surgery, even if correctly performed, is not sufficient to prevent the risk of local recurrence of rectal cancer. They believe that routine adjuvant radiation therapy after surgical treatment of rectal cancer should improve survival rate. PMID- 1755595 TI - [Gastric emptying after duodenogastric resection]. AB - The gastric emptying has been studied with 99Tc labelled in 35 patients followed for 2-8 years after duodenogastric resection. All patients had been undergone a gastric resection of 2/3 of stomach. In 18 had been performed a Billroth II (BII) and in 17 a gastrojejunostomy with a Roux-en-Y anastomosis. The jejunal loop had been carried out about 25-35 cm from the Treitz, the mesenteric margin isolated for 2-3 cm and the jejunojejunostomy performed about 50 cm from the gastrojejunostomy. Nobody complained symptoms from altered gastric emptying. In all patients with Roux-en-Y anastomosis there was an intense radioactivity in the new stoma till the 150th minute, and peristaltic activity was valid and coordinated. In patients with BII there was no radioactivity in the new stoma before the 150th minute, and peristaltic activity was always convulsive and uncoordinated. PMID- 1755596 TI - [Clinical research on the possibility that renal cysts may be responsible for the appearance of hematuria]. AB - New techniques of study, namely echography, urography, TC, give evidence of a great number of asymptomatic renal cysts in the everyday experience. Then also if haematuria was classically considered one of the symptoms of renal cysts, there are now many reasons to consider such evidence very infrequent, and downright there are some valid doubts that renal cysts may cause haematuria at all. So the authors have analysed 113 patients, most of them coming from Institute of Radiology of Chieti University Faculty of Medicine; all of them had renal cysts diagnosed by echographs and/or urography but only a minority were just from the beginning studied for haematuria, whereas the majority for many different symptoms. Total cases was then divided into two groups: one of 102 patients, all without haematuria; 78 of them had been studied only with echography, whereas other 24 patients had been examined both with echography and urography. The second group, of 11 cases, included all the patients who had both renal cysts and haematuria. Only in two cases of this second group was lacking evidence of any associated pathology which must be responsible for haematuria, whereas in all the other 9 cases a different aetiology of the haematuria was demonstrated, for simultaneous presence of various pathologies (cystopyelitis with associated prostatis, haemorrhagic cystitis, bladder diverticula and renal papillomas and upper urinary ways tumours), all much easier responsible by themselves of haematuria, also if with different features from case to case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755597 TI - [Fractures of the calcaneus. The indications for surgical treatment]. AB - The authors report the results obtained from a study of 41 cases of calcaneal fractures. Surgical treatment, when possible, is to be applied because it allows a satisfactory reconstruction of the subtalar and calcaneocuboid joint. The choice of various surgical methods is facilitated by computerised tomography which allows a precise assessment of the calcaneum. The quality and the stability of the reduction determine in a significant way the functional result. PMID- 1755599 TI - [Primary hepatic actinomycosis: a clinical case report and review of the literature]. AB - Primitive actinomycotic abscess of the liver is extremely rare: in the world literature are reported twenty cases. The authors report a case of a 73-year-old patient admitted at our hospital in poor general conditions, with twelve kilograms weight loss in the last year, recurrent fever and tenderness in right hypochondrium. CT scan, ultrasonography and angiography showed the presence of a seven-centimeters hypovascularized mass in the fourth segment of the liver. The patient was submitted to surgical segmentectomy of the fourth segment. The histologic examination and the histochemical colorations made on the specimen have given the diagnosis of hepatic actinomycotic abscess. No clinical evidence of other intra-abdominal or extra-abdominal localizations were found. From 1928 to date only twenty similar cases have been reported in the world literature. The mean time between the beginning of the symptoms and the diagnosis was 11.1 months (range: 2-54 months): this to confirm the diagnostic difficulties of the disease. The hepatic lesions are described as single in eight cases and multiple in thirteen. Thirteen patients have been treated only with medical therapy: nine recovered and four died for disease spread. Of the six patients with resectable lesion treated surgically, five recovered and one died for pulmonary recurrence. PMID- 1755598 TI - [Splenectomy for hemorrhage from esophageal varices with massive thrombosis of the portal bed in the absence of cirrhosis: an intervention to be reevaluated? Reflections on a clinical case]. AB - It has been suggested that the ideal definitive treatment of hemorrhage from esophageal varices due to extrahepatic portal hypertension should be a selective shunt, avoiding splenectomy, when possible, for its unfavorable effects. We present a case with extrahepatic portal hypertension and polycythemia vera who complained acute recurrent variceal bleeding in spite of multiple sclerotherapy sessions, with a massive thrombosis of the portal bed and radicles without any possibility to perform a shunt. The combined treatment was emergency splenectomy followed by a closed program of sclerotherapy. The result was good at two years of follow-up. The optimal treatment of patients with episodes of bleeding varices for extrahepatic portal hypertension and patency of splenic vein should be a selective shunt; poor long-term results have been reported in patients without patency of the major tributaries of the portal system and treated with other operations than shunts. Splenectomy could gave a role in producing these unhappy results. After splenectomy it has been observed an increased thrombocytosis, venous infarction of the bowel, increased susceptibility to infection and also a paradoxical higher risk of bleeding by removing low risk collaterals. From this anecdotal report it can be argued that splenectomy is not necessarily followed by bad results and can be the first therapeutic option in emergency and in some selected cases with huge, high risk varices, difficult to treat by sclerosis only, and without suitable vessel for a shunt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755600 TI - [Surgical central venous catheterization (SCVC) for total parenteral nutrition (TPN) via the basilic vein]. AB - The central venous catheterization (CVC) by subclavian vein puncture for total parenteral nutrition (TPN) has a high risk of complications in some situations such as neck or supraclavicular diseases, tracheostomies, costoclavicular deformities and coagulopathies. Surgical CVC approach to the basilic vein is indicated in these cases. The aim of this study was to evaluate the usefulness of this technique. Sixteen patients had TPN with this technique, utilizing a silicon catheter (Vygon Nutricath). The main time of TPN was 19 days (min 5-max 41). In 12 cases (75%), there were no complications. In two cases (12.5%) we observed an accidental catheter displacement. The incidence of thrombophlebitis was 12.5% (2 cases); in one of two cases (6.25%), it was correlated with the contamination of the catheter (Staphylococcus epidermidis); in the second case it was aseptic. Our results demonstrated the usefulness of this of these technique in cases in where the CVC by subclavian vein presents a high risk of complications. PMID- 1755601 TI - [Radioimmunoguided surgery. Presentation of the topic]. PMID- 1755602 TI - [The new prospects for radioimmunoguided surgery: the avidin-biotin system]. PMID- 1755603 TI - [Radioimmunoguided surgery in hepatic resection interventions for metastases of colorectal tumors]. PMID- 1755604 TI - [FO23C5 anti-CEA (FAb'2) 125-I monoclonal antibody for the intraoperative localization of colorectal tumors during radioimmunoguided surgery (R.I.G.S.)]. PMID- 1755605 TI - [The role of B72.3 125-I monoclonal antibody in the radioimmunoguided surgery of colorectal neoplasms]. PMID- 1755606 TI - [Neuroendocrine carcinoma of the skin]. AB - The neuroendocrine carcinoma of the skin (NCS) is an uncommon disease, having been described about 400 cases in world literature. Two cases of NCS in a 52-year old woman and in a 44-year-old man are reported; their histogenesis is still uncertain. It is advisable a wide cutaneous excision of the neoplasm extending 2 3 cm. over its macroscopic borders, in order to decrease the incidence of local recurrences, reaching 33% in some reports; when regional nodes are involved a lymphadenectomy is recommended. The authors also recommend a prophylactic radiotherapy of locoregional node chains, because of the high radiosensitivity of these tumors. PMID- 1755607 TI - [The endoscopic treatment of gastric adenomas]. AB - Endoscopic polypectomy is the treatment of choice in symptomatic polyps of the stomach. From 1974 to 1989, at the Endoscopy Division of National Cancer Institute of Milan, 37 patients underwent endoscopic polypectomy, to remove 55 gastric adenomas. Areas of malignancy were revealed in 3 patients. Two of them, not operable for advanced age and poor general conditions, are controlled endoscopically. Endoscopic polypectomy can be performed on an outpatient basis or with a short period of hospitalization. It represents the only form of therapy in not operable patients. Furthermore this method allows to prevent the malignant transformation of the adenomas, which, as reported in the literature, ranges between 3.4% to 66.5%. Our experience confirms the validity of this technique which is safe and effective. PMID- 1755608 TI - [Complicated jejunoileal diverticulosis. A clinical case report]. AB - The diverticulosis of jejunum ileum is an uncommon pathology, that is often revealed just from the complications which it presents. The clinical case reported by the Authors describes a woman who reached to admission for a serious condition of shock secondary to a jejunum bleeding diverticulosis and who underwent an intestinal resection. The patient was discharged home on IX p.o. day. From the review of literature results that the incidence of the diverticulosis of jejunum ileum consists of 0.1%-0.11% of all the gastrointestinal's diverticula and the predominance is for the female, especially in the middle age. The diverticulosis of jejunum ileum can be congenital or acquired; the first one came to the antimesenteric side of the intestines, the second one to the mesenteric side of the same. The diverticulosis is generally asymptomatic, but often produces many complications as the intestinal occlusion, secondary to a bridle, a volvulus, an invagination, also if the peritonitis caused by a diverticulosis's perforation represents the most frequent complication of them. Others rarest complications are the massive haemorrhage of diverticula, the stagnant loop syndrome, the malabsorption's syndrome due to lack of B12 vitamin and growth of bacteria within them, the diverticulitis caused by infection. The therapy of all complicated cases of jejunum ileum diverticula is necessarily the surgery only and exactly the intestinal resection. PMID- 1755609 TI - [Preoperative transhepatic biliary drainage in the jaundiced patient: our experience]. AB - The authors assessed the efficacy of PTBD in a group of 72 patients with obstructive jaundice due to lithiasis or malignant obstruction, that underwent preoperatively PTBD procedure. They analysed the early and late complications and its effectiveness in decreasing the bilirubin levels. The results, in agreement with the most recent reports, suggest the uselessness of the preoperative PTBD in the treatment of the patients with a jaundice due to a biliary lithiasis. Concerning the patients with a neoplastic jaundice, this procedure seems to be more effective in the patients with a biliary obstruction due to pancreatic head or distal choledochus carcinoma: in the patients with a far advanced cancer, the PTBD procedure could be the first step to the insertion of biliary endoprosthesis; on the other hand, in the patients that may undergo a curative treatment, PTBD could be useful preoperatively both to reach an adequate water electrolyte [correction of hydroelectrolithic] balance and nutritional status both to complete the diagnostic procedure. PMID- 1755610 TI - [Perioperative antibiotic prophylaxis in reconstruction of the thoracic wall]. AB - Thirty youngs and children were submitted to surgical reconstruction of excavated chest. To prevent risk of infections (by Staphylococcus and mixed gram-negative flora) preoperative 100 mg/Kg body weight of cefotaxime was given. In all patients the operative wounds healed regularly. To evaluate cefotaxime level and that of its metabolites raised in the tissues, the very sensibles method HPLC was applied. Thus 45 minutes after antibiotic somministration, very high levels were present in cartilage 9.8 mmg/gr and in bones (9.3 mmg/gr). Related to Staphylococcus aureus (MHK 90 of about 2 mmg/ml) results are of value also for other surgical orthopedic operations. PMID- 1755611 TI - Intraocular pressure--the cardiac connection. AB - A retrospective analysis of graphic intraocularpulse waves (IOPW) taken with a pneumotonograph (PTG) revealed abrupt elevations of intraocular pressure (IOP) in a strict-time relationship with the onset of spontaneous or sustained cardiac tachyarrhythmias. This may be explained as a consequence of an increase in central venous pressure from the "back" pressure effect of abnormal diastolic indexes of cardiac function rather than the forward systolic forces (including systolic blood pressure that usually are depressed under these circumstances). Given the frequency of cardiac arrhythmias in the general population, we suggest that continuous graphic IOP tracings, such as with the PTG, will reflect overall IOP levels better than those obtained, for example, by a quick-acting noncontact tonometer. Abnormal indexes of diastolic cardiac function found in many forms of heart disease, including the aging process, merit further consideration as a potential cardiovascular factor affecting ocular pressure dynamics in other circumstances. PMID- 1755612 TI - Critical evaluation of therapeutic keratoplasty in cases of keratomycosis. AB - Therapeutic keratoplasty was done in 123 neglected cases of fungal ulcers that did not respond to maximal medical therapy. It is recommended that, if the surgery is contemplated, it should be done before the ulcer perforates. A 0.5mm larger donor graft than recipient bed is better than a similar-sized graft. Various complications and final results are discussed. PMID- 1755613 TI - The use of a new portable noncontact tonometer in home tonometry. AB - We used a new portable noncontact tonometer for home tonometry on 26 patients with chronic open-angle glaucoma or suspected low-tension glaucoma. In an outpatient setting, the mean difference and correlation coefficient between the family member's noncontact tonometry values and the nursing staff's applanation tonometry values used as a control was 1.0mmHg and 0.894mmHg, respectively. The difference between the means was not statistically significant (P greater than .05, by Student's t test). At home, the variances of four noncontact tonometric values obtained every other hour did not differ significantly from those obtained in the outpatient setting by the nursing staff (P greater than .05). Five of 26 patients had their medical regimen changed based on the results of home tonometry. This study suggests that many nonmedical personnel can do noncontact tonometric scanning reliably. At home, noncontact tonometry may help evaluate a patient's intraocular pressure control. PMID- 1755614 TI - Adipose tissue in the lens. AB - A case of persistent hyperplastic primary vitreous with replacement of the lens by adipose tissue was observed in a 31-year-old man. A review of the literature revealed only two other cases in which this particular finding was documented. PMID- 1755615 TI - Laser-assisted tarsoconjunctival flap harvesting for lower eyelid defect reconstruction. AB - Tarsoconjunctival flap procedures are reliable and versatile procedures for reconstruction of large lower lid defects. We present a new carbon dioxide laser assisted flap-harvesting technique. This technique combines precise and accurate incisions with simultaneous complete hemostasis. We have done carbon dioxide laser-assisted flap harvesting for large and total lower lid defects. The hemostatic evaporative cutting of the carbon dioxide laser decreases time, swelling, and bleeding in obtaining tarsoconjunctival grafts and flaps. PMID- 1755616 TI - Etiology of reduced visual acuity in congenital nystagmus. AB - A study was undertaken to identify the etiologic factor of reduced visual acuity in congenital nystagmus. Fourteen children with congenital nystagmus and reduced visual acuity were examined, using a modified "E" game test. Their success rate in identifying vertical lines was compared with their success rate in identifying horizontal lines. The children identified both vertical and horizontal lines with a similar rate of success. These results may indicate that poor vision in congenital nystagmus patients is partly the result of amblyopia. PMID- 1755617 TI - [Splenectomy for chronic thrombocytopenic purpura]. AB - During the period 1985-1989, 49 patients underwent splenectomy for chronic idiopathic thrombocytopenic purpura in our department. A correct follow-up was available for 39 patients. All patients had been previously treated with corticosteroids. We evaluated the platelet count one year after the operation and the relation between this count and several preoperative and postoperative factors. We observed a favourable prognosis when the preoperative study of platelet sequestration showed splenic destruction, when the duration of symptoms was less than one year and when there was a rapid increase in the platelet count during the first week after the operation. PMID- 1755618 TI - [Surgery for lung metastases in children]. AB - The authors report a series of 76 children with lung metastases followed from 1974 to 1989. Forty-four children were operated on with 64 thoracotomies (50 wedge resections, 5 segmentectomies, 2 pneumonectomies, 6 biopsies, 1 excision of an inflammatory granuloma): 23 of these children are alive, and 17 of them without any adjuvant radiotherapy. Thirty-two were not operated on; of the 13 that are alive, 7 had no adjuvant radiotherapy. The indications for surgery were: to treat a complication of the metastasis, to verify persistent images on CT scan, but essentially to avoid more aggressive treatment (chemotherapy, radiotherapy) with its risk of sequelae in children. PMID- 1755619 TI - [Chest injuries in children. Apropos of 93 cases]. AB - Ninety-three cases of thoracic trauma (age ranging from 1.1/2 to 15 years) were observed over a 10 year-period (1980-1990): 86 cases of blunt trauma and 7 cases of perforating injuries. Road accidents were the most prevalent (63 cases) followed by home and sport injuries (9), falls (9), perforating trauma (9) and others. Associated lesions were frequent: skeletal (67), abdominal (19), and head injuries (5)--the latter influence the vital prognosis. Rib fractures were observed in 60% of cases of blunt trauma (86). Pulmonary lesions were as follows: pneumothorax (41), hemothorax (21), and lung contusions (29). In 48 cases, several of these pulmonary lesions were associated. Diagnosis and therapy problems were encountered in 21 cases. Results were as follows: 3 deaths, within 24 hours due to hemorrhage (1 case with aortic lesion). FOLLOW-UP: 85 good results, 5 sequelae, without any clinical consequence--either pleural (2), diaphragmatic (2), or lung (1). The treatment was as follows: none (27), pleural aspiration (2), thoraco-synthesis by drain in other cases for 2 to 9 days. Surgery was necessary in 10 cases, with 2 thoracotomies, 1 orthopedic traction, 1 embolization of iliac artery. PMID- 1755620 TI - [Aneurysms of the aortic arch. Experience of 19 cases]. AB - From 1980 to 1990, 19 consecutive patients were operated for chronic aneurysm of the aortic arch: 16 men and 3 women with a mean age of 46 years (range: 20 to 72 years). Four aneurysms were proximal, with a distal limit in the left common carotid artery; 4 were distal, starting beyond the brachiocephalic trunk and 11 involved the entire aortic arch. Three were atheromatous, 9 were dystrophic, 1 was syphilitic, 1 was post-traumatic, 1 was secondary to coarctation and 4 was secondary to longstanding dissection. Four cases (21%) were in a state of pre rupture. They were all operated under cardiopulmonary bypass with profound hypothermia and circulatory arrest in 11 cases (9 cases of aneurysm involving the entire segment II and two cases of distal aneurysms). Selective cannulation of the large cervical arteries supplying the brain was performed in 5 cases (3 cases of proximal aneurysms and 2 cases of aneurysms of the entire segment II). Seven patients simultaneously underwent aortic valve replacement and replacement of the ascending aorta. One patient underwent replacement of the descending aorta and another underwent an ascending aorta-supracoeliac aorta bypass graft. The early mortality was 10.5% (2 patients out of 19) and the late mortality was 5.8% (1 patient out of 17). The mean follow-up was 46 months (maximum: 9 years, minimum: 9 months), and the 9-year actuarial survival rate was 86%. This study demonstrated the superiority of selective carotid cannulation as a means of cerebral protection. PMID- 1755621 TI - The geriatric patient in surgery. Experience with patients over the age of 85 years. AB - Between 1982 and 1989 hospitalized treatment was applied to 615 patients aged between 85 and 101 years. The average age was 88.8 years. Operations were performed on 406 of them (66.1%). The surgical lethality amounted 16.5%. The lethality in conjunction with emergency operation was as high as 30.8% or as low as 10.7% in the context of elective operations. X-ray findings recorded from heart and lung as well as ECG provided reliable criteria for assessment of the surgical risk. PMID- 1755622 TI - [Spontaneous and instrumental perforations of the thoracic esophagus (non neoplastic, non-caustic). Apropos of 20 cases]. AB - The authors present twenty cases of spontaneous or instrumental perforation of the thoracic esophagus (neoplastic and caustic perforations excluded). The delay before treatment was less than 24 hours in only one case. Mortality rate was 15%, concerning three patients (three cases of Boerhaave's syndrome) treated by T tube drainage. The contribution of exclusion using stapling technique should increase the indications of direct suture, which remains elective treatment. Esophagectomy retains its indications for perforations with pathologic esophagus or late diagnosis. PMID- 1755623 TI - [Benign mucus-secreting tumors of the appendix. Six cases]. AB - The authors report six cases of mucus-secreting tumor of the vermicular appendix, in four women and two men (mean age 59 years). All were benign. Pain in the right lower quadrant was the initial sign in 4 cases, while the mucus-secreting tumor was an incidental finding in the other two cases. A mass was palpated in the right lower quadrant in one case. A barium enema was performed in four cases and showed an extrinsic compression of the caecal base in one case, and of the right colon in another case. Four appendectomies, one associated with removal of the adjacent caecal tissues and two right colectomies were performed. Analysis of these six cases and a review of the literature allow us to recall the histologic classification of these tumors, which determines the prognosis and to emphasize the sonographic and CT scan findings which might lead to earlier preoperative diagnosis in the future. Management depends upon the circumstances under which the tumor is discovered, the local anatomy, and the type of tumor. Appendectomy is the treatment most often performed. Faced with a tumor of the appendix, without histologic proof or when the local anatomic conditions increase the risk of opening an abscess, right colectomy is recommended. PMID- 1755624 TI - [Complicated hydatid cysts of the liver]. AB - In 328 cases of hydatid disease of the liver operated between 1979 and 1989, 51 (15.8%) had complicated cysts. The most frequent complication was intrabiliary rupture (2/3 of all complications). The others were intraperitoneal rupture in 7 cases (13.8%), suppuration in 7 cases (13.8%) and intrathoracic rupture in 3 cases (5.8%). Among the intrabiliary ruptured cysts, T-drainage was performed in 15 cases, choledochoduodenostomy was performed in 12 cases, and sphincteroplasty was performed in 7 cases. The cases of intraabdominal rupture were operated immediately. The suppurated cysts were marsupialized in 3 cases and drained in 4 cases. The 3 cases of bronchobiliary fistula were treated by T-tube drainage of the common bile duct, drainage of the pleural space, repair of the diaphragm and closure of the communicating bronchus. In this series, the mortality rate was 7.8% and the recurrence rate was 9.8%. PMID- 1755625 TI - Gastroenterological options in faecal incontinence. AB - Faecal incontinence may be due to a trauma, a rectal prolapse, or a neurological disorder. Obstetric trauma: If the sphincter has been severed, direct repair is indicated. In the case of neurological damage, plication of the levators can provide significant improvement; while the post-anal repair has become popular, anterior sphincter plication and levatorplasty, provide equivalent results. Rectal prolapse: Full thickness rectal prolapse is frequently associated with incontinence. Two categories of operations have been described: local operative procedures (Delorme's plicature, perineal resection) provide poor results in term of restoration of continence and should be reserved to unfit and elderly patients; abdominal operations combine an extensive rectal mobilisation and they differ by the type of fixation. The Ripstein operation (fixation to the promontory by an encircling sling of non absorbable mesh) has long been popular in the United States, but is followed by severe constipation. In the simple suture rectopexy, the rectum is fixed to the pelvic floor and the presacral fascia by non absorbable procedures. In the Ivalon sponge rectoprexy, a polyvinyl alcohol mesh in secured between the sacrum and the rectum, and provides a dense fibrous reaction. In the antero-posterior Marlex rectopexy, a sheet of Marlex mesh is fixed posteriorly to the rectum, and a sling is interposed anteriorly in order to support the anterior wall. In the resection rectopexy, a sigmoid resection in added to the rectal fixation in order to suppress the redundant sigmoid which is responsible for the constipation frequently following rectopexy. Results of abdominal rectopexy are satisfactory in terms of recurrence and restoration of continence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755626 TI - [Mediastinal exploration for hyperparathyroidism]. AB - Five per cent of parathyroid adenomas are situated in the mediastinum. Many of them are accessible via a cervical incision: virtually all posterior mediastinal adenomas, by dissecting well behind the oesophagus, and most intrathymic adenomas, by cervical exteriorisation of the thymus. Finally, the indications for sternotomy are are: less than 2% of operations for hyperparathyroidism. After describing the technical details, the authors review the indications, the imaging modalities used and the results of their last 20 sternotomies. PMID- 1755627 TI - [Popliteal vascular trauma: therapeutic management]. AB - The functional severity of popliteal artery injury is intimately related to the direct consequences of tissue ischaemia increased by the associated traumatic attrition. The conservation of a functional limb requires: limitation of the duration and repercussions of ischaemia, by the use of a rigorous therapeutic protocol; "functional" surgical or even microsurgical reconstruction whose limits are still confused with the degree of traumatic myolysis and the potential of nervous recovery. Therefore, it seems obvious that the major difficulty lies in the definition of the limits for limb preservation. PMID- 1755628 TI - [The superior mesenteric artery syndrome. Apropos of a case and review of the literature]. AB - During laparotomy for an appendicular peritonitis, the authors found an acute mesenteric artery syndrome. Conservative treatment consisted of mobilisation of the 4th part of the duodenum with section of the suspensory muscle of Treitz, but this was not sufficient to cure the patient. Two weeks later the patient completely recovered after a duodenojejunal anastomosis. A review of the literature confirmed that surgical treatment for scoliosis and anorexia nervosa play an important role in the aetiology of this disease. PMID- 1755629 TI - [Multinodular pulmonary type AL amyloidosis. Report of a case and review of the literature]. AB - A multinodular lung lesion was discovered in a healthy 56 year-old man on routine chest X-rays. Histology revealed multinodular amyloidosis which histochemically was found to correspond to the AL type. This type of amyloidosis raises the differential diagnosis ith a lung neoplasm. In our case, no cell dyscrasia was observed. The patient was treated by surgery as recommended in the literature. PMID- 1755630 TI - [Reimplantation of a non-functioning lung. Report of a case]. AB - The authors present the case of a patient with a carcinoid tumor of the left main bronchus. Conservative surgery by sleeve resection without pulmonary resection was performed. The underlying lung which was considered to be nonfunctioning during pre-operative evaluations, completely recovered within a year following surgery. PMID- 1755631 TI - [Technique and results of lung transplantation in rats]. AB - Lung transplantation has recently emerged as an efficient therapy for a variety of endstage pulmonary diseases. Nevertheless, many problems remain unsolved. A simple and reproducible experimental model allows examination of some of the problems encountered. We report here our experience of lung transplantation in the rat. One hundred and thirty six lung transplantations have been performed. After the initial phase necessary to master the technique, an overall survival rate of 86% was achieved. Graft function, as assessed by chest X-rays and lung isotope scans, was satisfactory up to 4 months after transplantation. Lung transplantation in the rat is a reliable and reproductible experimental model allowing the development of research projects in this field. PMID- 1755632 TI - [Posterior cardiopexy technique]. AB - The technique of Hill's posterior cardiopexy is based on precise anatomical criteria. Hill's "strips" actually correspond to the peri-oesophageal connective tissue described by Boutelier. The operation consists of closing the oesophageal hiatus and attaching the "strips" to the preaortic fascia. We prefer to perform the operation via a left subcostal incision without intraoperative manometry and we complete the procedure by fixing the fundus of the stomach to the left side of the oesophagus. PMID- 1755633 TI - Smoking in children. PMID- 1755634 TI - Acute appendicitis in the preschool child. PMID- 1755635 TI - Screening for neuroblastoma. PMID- 1755636 TI - Height reduction in 539 tall girls treated with three different dosages of ethinyloestradiol. AB - During the period 1970 to 1985, 539 constitutionally tall girls were treated with ethinyloestradiol in varying dosages to reduce final height. They all had a predicted final height above 181 cm (greater than +2.5 SD). The girls were all healthy and were treated with three different dosages of ethinyloestradiol. Throughout these 15 years recommended treatment regimens changed, and the treatments described followed these guidelines. Girls in group 1 (n = 263) were treated with 0.5 mg of ethinyloestradiol, group 2 (n = 178) with 0.25 mg, and group 3 (n = 98) with 0.1 mg. The total mean (SEM) reduction of final height was 5.9 (0.2), 5.3 (0.1), and 4.4 (0.2) cm when treated with 0.5, 0.25, and 0.1 mg respectively. Group 1 was treated for 2.02 (0.03) years and group 2 and 3 for 1.85 (0.04) and 1.63 (0.05) years respectively. When expressed in relation to the treatment period the reduction of final height was 3.0 (0.1), 3.1 (0.1), and 2.9 (0.2) cm/year of treatment respectively. All the girls were treated with ethinyloestradiol as a daily single dose, while progestogen was given daily the first 10 days of every month. In conclusion we found that a daily dose of ethinyloestradiol 0.1 mg for about 20 months is sufficient to reduce final height. We recommend starting treatment at a bone age of about 12 years. PMID- 1755637 TI - Cyclical disturbance of diabetic control in girls before the menarche. AB - Seven diabetic girls who presented with cyclical disturbance of diabetic control before the menarche are described. In six girls cyclical hyperglycaemia occurred and in one cyclical hypoglycaemia. The index case is described in detail, and is then included in a description of the main clinical features of all seven cases. Cyclical disturbance of diabetic control may present in diabetic girls from age 9 years onwards. Home blood glucose monitoring records may reveal cyclical disturbance, usually hyperglycaemia, and usually occurring at 21-34 day intervals and lasting for two to five days. Serious illnesses and hospital admission can be averted by educating parents to make appropriate changes to insulin regimen or diet. Our hypothesis is that the disturbance of diabetic control is caused by the onset of cyclical hormonal changes, a 'menstrual' cycle before menstruation. The precise mechanism for the changes in carbohydrate tolerance is unknown. PMID- 1755638 TI - Covert bacteriuria: long term follow up. AB - In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In girls with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment. PMID- 1755639 TI - Urinary tract infection in febrile convulsions. AB - A retrospective review of the casenotes of 403 children admitted to hospital with febrile convulsions was performed to estimate the frequency of symptomatic urinary tract infection and examine medical practice in making this diagnosis. A total of 228 (56%) children had urine cultured: 150 bag specimens, 76 clean voided samples, and two suprapubic aspirates. There were 13 'probable' and six 'possible' infected urine samples together representing 5% of the whole study population (n = 403), 8% of those having urine cultured (n = 228), and 12% of those providing uncontaminated urine samples (n = 155). Those with first febrile convulsions and those aged under 18 months were more likely to have urine examined. Practices varied significantly between different hospitals. These results suggest that there has indeed been a need for practice guidelines, and that further audit of practice is required to assess their impact. PMID- 1755640 TI - Maternal and fetal influences on blood pressure. AB - To study maternal and fetal influences on blood pressure in childhood 405 children aged 4 years who were born and still resident in the Salisbury health district were visited at home for blood pressure and growth measurements. Information on the pregnancy, delivery, and baby was abstracted from the routine obstetric notes. Similar to recent findings in adults, the child's systolic pressure was inversely related to birth weight and positively related to placental weight. Systolic pressure at 4 years increased by 1.2 mm Hg for every SD decrease in the ratio of head circumference to length at birth, and by 1.1 mm Hg for every SD decrease in ponderal index at birth. Mothers whose haemoglobin concentrations fell below 100g/l during pregnancy had children whose systolic pressures were on average 2.9 mm Hg higher than the children of mothers with higher haemoglobin concentrations. Patterns of placental weight, birth weight, head circumference, and length that are associated with high blood pressure in adults are also associated with higher blood pressure in 4 year old children. Identification of the intrauterine influences that lead to these patterns of fetal growth could lead to the primary prevention of hypertension. PMID- 1755641 TI - Deficiency of prostacyclin production in meningococcal shock. AB - A deficiency of prostacyclin (PGI2) production by the vascular endothelium might underline the severe vasoconstriction and intravascular thrombosis that characterise meningococcal shock. The effect on PGI2 synthesis by human umbilical vein endothelial cells (HUVEC) in culture was examined in sera from children with meningococcal shock, healthy adults, and children with other febrile illnesses. In comparison with adult controls, PGI2 synthesis was reduced when HUVEC were incubated with the sera from 10 of 13 patients with meningococcal shock. A similar defect was observed with only four of 20 sera from children with other febrile illnesses. The effect of sera from patients with meningococcal shock on HUVEC was reversible with normal serum, and seems to be due to the absence of a factor necessary for PGI2 production rather than an inhibitor. These findings suggest that a deficiency of PGI2 may have a role in the pathogenesis of meningococcal shock and that exogenous PGI2 may be of therapeutic benefit. PMID- 1755642 TI - Hyperganglionosis mimicking Hirschsprung's disease. AB - Three patients with hyperganglionosis are reported in whom an initial diagnosis of Hirschsprung's disease was suspected. In one patient there was a classic presentation with constipation, in another Hirschsprung's disease coexisted, and in the third the initial inadequate suction rectal biopsy specimen was suggestive of Hirschsprung's disease on acetylcholinesterase staining. Evidence of hypertrophy and hyperplasia of the intermuscular and submucosal plexuses on a full thickness bowel biopsy specimen was used to confirm the diagnosis of hyperganglionosis, suggested by the characteristic demonstration of moderate increase in the number of acetylcholinesterase stained nerve fibres in the lamina propria mucosae on rectal biopsy. Surgical management was guided by clinical signs. Two patients had colonic resections; the third had temporary stomal diversion. Hyperganglionosis is rarer than Hirschsprung's disease but is known to mimic it. We suggest full thickness bowel specimens are needed to confirm the diagnosis and that inadequate rectal suction biopsies must be interpreted with caution. PMID- 1755643 TI - Trends in prevalence and survival of very low birthweight infants, England and Wales: 1983-7. AB - Between 1983 and 1987 over 99% of all infants born in England and Wales had their birth weights recorded when the birth was registered. Trends in occurrence and one year survival of those who weighed under 1500 g at birth have been calculated in 100 g groups, separately for single and multiple births. By 1987 singleton live births in England and Wales who weighed between 700 and 799 g had a 43% chance of surviving to 1 year compared with a 32% chance five years earlier; those who weighed 800 to 899 g had a 55% chance compared with 46%. The absolute number of survivors weighing between 500 and 999 g at birth increased by nearly 50% between 1983 and 1987, and there was a 30% increase overall in survivors weighing less than 1500 g. PMID- 1755644 TI - What do parents expect antenatally and do babies teach them? AB - Antenatal inquiry of 658 parents in the North Staffordshire District Health Authority showed at least 13% to lack knowledge about a baby's potential for personal interaction when under 1 week old. Mothers and fathers varied significantly, independent of parity. Experienced parents expected later smiles. Two hundred and seventy eight of the same families were questioned three to four months after birth. Most parents had observed their baby's early responsiveness. Specific responses (Looking, listening) were noted earlier when anticipated and looked for. Significant among postnatal non-responders was their antenatal selection of predominantly impersonal stimulation for a baby. The greatest degree of warmth noted in postnatal observations correlated notably with a father's antenatal interest and postnatal support from him and their friends, a mother's commitment to breast feeding and her knowledge that a very young baby can see, like faces, and cries for emotional reasons. This highlights areas for antenatal tuition and postnatal encouragement, aiming to enhance warm early mutual regard between parents and child. PMID- 1755645 TI - Inherited metabolic diseases in the sudden infant death syndrome. AB - All sudden, unexpected infant deaths presenting during a two year period within a defined geographical area in Avon and north Somerset were investigated for inherited metabolic disease. Of 95 deaths, 88 were classified as cases of sudden infant death syndrome (SIDS). In addition to the normal postmortem investigations, samples of cerebrospinal fluid, urine, vitreous humour, and skin were collected for metabolic studies. No abnormal organic acid metabolites were found in the fluids from the 88 cases of SIDS. Fatty acid oxidation was assessed in skin fibroblasts from 70 cases of SIDS, but no examples of medium chain acyl CoA dehydrogenase (MCAD) deficiency were found. One case with abundant glycogen in the liver was subsequently diagnosed as having glycogen storage disease type 1c. These findings suggest that the incidence of MCAD deficiency and other metabolic diseases in SIDS is much lower than previously claimed. PMID- 1755646 TI - Transoral decompression and posterior stabilisation in Morquio's disease. AB - A 3.5 year old boy with Morquio's disease was referred with a persisting left hemiparesis four months after a fall and was found to have craniocervical junction compression due to atlantoaxial subluxation and significant anterior soft tissue compression. Transient unconsciousness at the time of the fall was probably due to medullary concussion as a result of hyperextension, not a head injury. Spinal cord compression due to atlantoaxial subluxation at the craniovertebral junction is a major cause of disability and death in these patients. Once cervical myelopathy appears, early posterior occipitocervical fusion has been advocated in order to arrest the progression of neurological disability and this is successful in most cases. This conventional approach was considered unsafe because of the significant anterior compression. A combined anterior transoral decompression with posterior fusion to deal with this particularly difficult problem is described. PMID- 1755647 TI - Complications of splintage in congenital dislocation of the hip. AB - The use of abduction splintage in the treatment of congenital dislocation of the hip has an important morbidity. Six children who developed complications are presented in this paper. Sustained splintage of an unreduced hip, overcorrection of the femoral head displacement, avascular necrosis of the femoral head, full thickness pressure sores, and excessive tibial torsion may occur as a consequence of treatment. Expert supervision of abduction splintage, correct case selection, and regular review are necessary to reduce the incidence of such complications. PMID- 1755648 TI - A practical method of serial bedside measurement of cerebral blood flow and metabolism during neurointensive care. AB - Acute encephalopathy is a major cause of death and neurological handicap in children. The principle aims of treatment are to provide adequate cerebral blood flow for the brain's metabolic needs and to prevent intracranial pressure rising above the level at which brain herniation occurs. Rational management requires an understanding of the pathophysiological changes in cerebral blood flow and metabolism which occur. The paucity of data on this subject reflects the perceived difficulty of measuring cerebral blood flow and cerebral metabolism in children. A modification of the Kety Schmidt technique of measuring cerebral blood flow and cerebral metabolism is described. This modification makes it possible to perform serial bedside measurements in children receiving intensive care. This method was used to perform 348 measurements in 58 children. The method was reproducible and no significant complications were encountered. The results indicated that appreciable changes in cerebral blood flow and metabolism could occur in individual patients over time, emphasising the importance of serial measurements. This technique may provide a practical means of monitoring cerebral blood flow and metabolism in very sick children receiving neurointensive care and evaluating the efficacy of treatment. PMID- 1755649 TI - New insights on gastro-oesophageal reflux in cystic fibrosis by longitudinal follow up. AB - A higher frequency (25%) of gastrooesophageal reflux (GOR) has been previously reported in patients over 5 years old with cystic fibrosis compared with controls without cystic fibrosis. It was believed that GOR was caused by the complications of cystic fibrosis. We looked for GOR in all 26 children younger than 60 months who had cystic fibrosis diagnosed. They had a classical genetic profile and the usual scattered clinical manifestations for age. GOR was confirmed in 21 (81%): 20 by abnormal pH tracings and in one on a clinical basis. After at least one month of adjusted cystic fibrosis treatment, antireflux treatment (cisapride) was given to 16 patients and variables of GOR improved dramatically. Weight gain was significant and recurrent cough and wheeze disappeared. One year later half of the patients still suffered from GOR. GOR is a major problem in the early life of those with cystic fibrosis and is not the consequence of either respiratory or gastrointestinal complications as it improves with age whereas cystic fibrosis becomes worse with age. PMID- 1755650 TI - Pregnancy in phenylketonuria: dietary treatment aimed at normalising maternal plasma phenylalanine concentration. AB - The transport characteristics of the placenta, which favour higher phenylalanine concentrations in the fetus than in the mother, and regression data of head circumference at birth against phenylalanine concentration at conception in maternal phenylketonuria (PKU), suggest that treatment of maternal PKU should ideally aim to maintain plasma phenylalanine concentration within the normal range throughout pregnancy. A patient with classical PKU was treated from before conception by aiming to maintain plasma phenylalanine concentration within the range 50-150 mumol/l and tyrosine within the range 60-90 mumol/l. The diet was supplemented with phenylalanine-free amino acids (100-180 g/day) and tyrosine (0 5 g/day). Plasma amino acid concentrations were monitored weekly by amino acid analyser. Dietary phenylalanine intake ranged from 6 mg/kg/day at conception to 30 mg/kg/day at delivery. Normal weight gain and fetal growth were maintained throughout the pregnancy. A normal baby was born at term with a head circumference of 35.5 cm; at 1 year of age no abnormality is detectable. These results show that with careful monitoring and compliance it is possible, and may be advisable, to maintain plasma phenylalanine concentration within the normal range in the management of PKU pregnancy. PMID- 1755651 TI - Subdural fat effusion complicating parenteral nutrition. AB - A preterm infant fed parenterally through a central venous catheter developed a subdural effusion containing fat emulsion. Subsequent postmortem examination failed to demonstrate any vascular abnormality that might have explained this rarely reported complication. Although retrograde flow of feeding solutions into cerebral veins seems a likely explanation, the exact mechanism remains uncertain. PMID- 1755652 TI - A national survey of nebuliser use. AB - Nebuliser drug delivery units were reused in 15% of paediatric wards participating in a national survey, while routine servicing and written information was provided by only half the wards issuing home nebulisers. Written information should be developed as a national resource, and further research on optimal cleaning practices is required. PMID- 1755653 TI - Familial infantile oesophageal achalasia. AB - Oesophageal achalasia is uncommon in children and in its familial form it is a rarity. The presentation and management of two male siblings who presented with oesophageal achalasia as infants are reported. A high degree of consanguinity in the parents of the children existed, suggesting autosomal recessive transmission. PMID- 1755654 TI - Populations and samples. PMID- 1755655 TI - Paediatric care in the United States. PMID- 1755657 TI - Archives francaises de Pediatrie. PMID- 1755656 TI - Lyme disease in paediatrics. PMID- 1755658 TI - Meningoencephalitis after measles-mumps-rubella vaccine. PMID- 1755659 TI - Gonadal function after allogenic bone marrow transplantation for thalassaemia. PMID- 1755660 TI - Computerised information systems. PMID- 1755661 TI - Equipment requirements for community based paediatric oxygen treatment. PMID- 1755662 TI - Septicaemia and adrenal haemorrhage in congenital asplenia. PMID- 1755663 TI - Dr Langdon Down. PMID- 1755664 TI - [Bone marrow changes at several stages of HIV infection, studied on bone marrow biopsies in 85 patients]. AB - Bone marrow biopsies from eighty-five patients with different stages of HIV infection were reviewed. Biopsies were generally indicated to evaluate peripheral blood abnormalities, but suspicion of lymphoma and other specific pathologies was another important indication. The histopathological features are described and are often suggestive of HIV infection but non-specific. Hypercellularity (72.9%), dysmyelopoiesis (78.8%), plasma cell hyperplasia (97.7%), lymphoid infiltration (27%) and histiocytosis with or without granulomata (11.7%) were the most striking abnormalities. Other frequent features include: increased stainable iron deposits, venous stasis and serous atrophy (gelatinous transformation). Marrow hypoplasia is rather infrequent (28.2%) and usually a terminal event of AIDS. Bone marrow biopsies revealed opportunistic and neoplastic complications in seven cases, with demonstration of pathogens in four cases (Mycobacterium avium, Cryptoccocus neoformans, Toxoplasma gondii and Leishmania donovanii) and malignant lymphomas in three other cases (one Burkitt's lymphoma and two Hodgkin's disease). Bone marrow biopsy provides useful information for the diagnosis and prognosis of HIV infection and for the diagnosis of complications. PMID- 1755665 TI - [Lipoma of the internal auditory canal. An anatomo-clinical case study and review of the literature about cranial nerve lipomas]. AB - A 36-year-old female presented with vertigo and worsening of a right hearing loss with tinnitus. Clinical and radiologic investigations revealed a tumor of the right internal acoustic meatus, first diagnosed as a neuroma. Histologic study of surgical samples led to a final diagnosis of lipoma. Cranial nerve lipomas are rare and usually located in the cerebellopontine angle. Lipomas confined to the internal acoustic meatus are much rarer. The review of the literature however, shows that their histologic characteristics and their behavior are identical to those of cerebellopontine angle lipomas, and that a minimal surgical resection is therefore advised. PMID- 1755666 TI - [Neuroendocrine tumors of the mammary gland. Current evaluation apropos of a case]. AB - The authors report a case of infiltrating non-mucinous neuroendocrine breast tumor of both nesidioid and carcinoid type, exclusively composed of argyrophil cells and showing estrogen receptors. By comparing it to those published in literature, they conclude that there are two types of breast tumors with argyrophil cells: one very rare, exclusively composed of neuroendocrine cells, which may present all of the morphological, functional, evolutive aspects and particularly the carcinoid pattern of diffuse endocrine system tumors; the other is more common, composite, reminiscent according to the abundance of their neuroendocrine components, either of the features of diffuse endocrine system tumors, or of those of conventional adenocarcinomas. Their findings help to explain that the combined hormonoreceptive and hormonosecreting nature of these tumors is the particular property of their neuroendocrine cells comparable to that of the pituitary gland. In the composite tumors, these cells are associated in symbiosis with the epithelial glandular cells which are of ectodermal origin. Such an association, also observed in other parts of the body, is not fortuitous but functional and thus could contra-indicate antiestrogen hormonetherapy. PMID- 1755667 TI - [Anatomopathological aspects of colorectal polyps in Cameroon]. AB - In order to present the main types of colo-rectal polyps in Cameroon, we reviewed all those cases received and examined in our Pathology laboratories during a six and a half year period (1st January 1984-30th June 1990). The polyps were sent by gastro-enterologists after resection during total colonoscopy, with information about age and sex of patients, signs and symptoms and sites and number of polyps. One hundred and two colorectal polyps were taken from 88 patients with a maximum of two polyps per patient. Out of these 102 polyps, we noted: 55 juvenile polyps (54%), 23 hyperplastic polyps (22.5%), 13 adenomatous polyps (12.5%), 10 inflammatory polyps (10%) and one polyp of the Peutz-Jeghers type. One case of hyperplastic polyposis and one of familial polyposis with adenomas on histological examination were registered. On the whole, juvenile polyps predominated and adenomas which can become carcinomas were less frequent than what is seen in Western developed countries. This may be due to the fact that the polyps we examined were only taken only from patients seen in outpatient department for gastrointestinal complaints. PMID- 1755668 TI - [Undifferentiated "embryonal" sarcoma of the liver. Apropos of a case with immunohistochemical study]. AB - The authors report a case of undifferentiated embryonal sarcoma of the liver, observed in a 25 year old man, in whom the diagnosis, established by histological findings, was confirmed at immunohistochemical examinations. The clinical and pathological features of these conditions are discussed. PMID- 1755669 TI - [Primary adenocarcinoma of the bladder. Apropos of 2 cases]. AB - The authors report two cases of primary adenocarcinoma of the urinary bladder with secretion of mucus, observed over a year period, between 1978 and 1990. The different histologic patterns are encountered: mucinous adenocarcinoma (colloid carcinoma), clear cell adenocarcinoma exhibiting glandular and trabecular or papillary patterns. They are often reminiscent of those seen in gastrointestinal tumors. The colloid carcinoma pattern is associated with intense schistosomiasis of the bladder. Macroscopic studies show budding and necrotic tumors, with infiltration and invasion of the musculosa. We agree with the role played by glandular metaplasia of the vesical urothelium that is accepted by the majority of the authors in the histogenesis of these tumors. PMID- 1755670 TI - Cardioplegia: from the bedside to the laboratory and back again. PMID- 1755671 TI - Human coronary, internal mammary, and gastroepiploic artery reactivity. PMID- 1755672 TI - University of Wisconsin solution for human donor heart preservation: initial clinical experience. AB - Although in vitro and primate orthotopic transplant experiments have suggested the superiority of University of Wisconsin solution (UWS) compared with crystalloid cardioplegia and saline solution storage for hypothermic heart preservation, concerns about the viscosity and the high potassium concentration of UWS have precluded its use in human cardiac transplantation. To test the safety and efficacy of UWS, 16 patients received hearts arrested with, flushed with, and stored in UWS at 4 degrees C for a mean ischemic time of 153.3 +/- 30.7 minutes. After reperfusion, the hearts contracted vigorously and attained a stable sinus rhythm within 4.0 +/- 2.4 minutes, and the patients were weaned from bypass in 24.5 +/- 8.0 minutes. There was no evidence of acute or chronic ischemic myocardial injury by enzymatic analysis, electrocardiography, or biopsy specimen histology. The results suggest UWS can be safely used, within currently accepted limits of donor ischemic time, to arrest and preserve human hearts for transplantation. Further studies of preservation are required to compare UWS with crystalloid cardioplegia and saline solution storage and to test the ability of UWS to prolong the period of safe donor hypothermic ischemia in clinical heart transplantation. PMID- 1755673 TI - Improved management of the Paget-Schroetter syndrome secondary to thoracic outlet compression. AB - For years, patients with "effort" thrombosis were treated by anticoagulants and conservative exercise; and if recurrent symptoms developed when they returned to work, they were considered for first-rib resection. Recently, use of thrombolytic agents with early surgical decompression of the neurovascular compression has markedly reduced morbidity, such as postphlebitic syndrome and the necessity for thrombectomy. A review of 67 patients seen over 25 years showed that 34 were initially treated with heparin sodium and then Coumadin (crystalline warfarin sodium). Recurrent symptoms developed in 21 after they returned to work and necessitated transaxillary first-rib resection to relieve symptoms. Eight also underwent thrombectomy. Recently, 33 patients were initially treated with thrombolytic agents and heparin, followed promptly by early first-rib resection. The evaluation and efficacy of this therapy have been established by frequent and repetitive venograms and careful follow-up of patients. Most of the patients showed improvement with thrombolytic agents. Remaining stenoses that suggested intravascular thrombosis were usually secondary to external compression of the vein by the clavicle, costoclavicular ligament, rib, or scalenus anterior muscle. Venous thrombectomy was necessary in only 4 patients in whom the clot was not controlled by thrombolytic therapy and operative release of compression. There were no deaths in the series. PMID- 1755674 TI - Malignant esophagorespiratory fistula: management options and survival. AB - The development of a malignant esophagorespiratory fistula is a devastating complication. Data comparing various treatment options in a large group of patients are sparse. To assess the results of therapy, we reviewed our experience in 207 patients with malignant esophagorespiratory fistula. Records of 207 patients admitted to our institution with malignant esophagorespiratory fistula from 1926 to 1988 were reviewed and results of management analyzed. Age ranged from 21 to 90 years (median, 59 years); the male/female ratio was 3:1. Primary tumor site was esophagus in 161 (77%), lung in 33 (16%), trachea in 5 (2%), metastatic nodes in 4 (2%), larynx in 3 (1%), and thyroid in 1. Symptoms and signs of malignant esophagorespiratory fistula included cough in 116 (56%), aspiration in 77 (37%), fever in 52 (25%), dysphagia in 39 (19%), pneumonia in 11 (5%), hemoptysis in 10 (5%), and chest pain in 10 (5%). Respiratory location of fistula included trachea in 110 (53%), left main bronchus in 46 (22%), right bronchus in 33 (16%), lung parenchyma in 13 (6%), and multiple sites in 5 (2%). The percentage of patients alive at 3, 6, and 12 months by treatment modality was 13%, 4%, and 1% for supportive care (n = 104); 17%, 3%, and 0% for esophageal exclusion (n = 29); 21%, 14%, and 0% for esophageal intubation (n = 14); 30%, 15%, and 5% for radiation therapy (n = 20); and 46%, 20%, and 7% for esophageal bypass, respectively. Patients treated with radiation therapy and esophageal bypass had a significantly prolonged survival compared with patients treated with the other modalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755675 TI - Weight is not an accurate criterion for adult cardiac transplant size matching. AB - Owing to the limited availability of donor hearts, standard donor criteria for heart size matching need to be reexamined. The current practice at most centers is to match the donor's body weight to within +/- 20% of the recipient's. Our hypothesis was that minimal differences exist in heart sizes of the adult donor population, and therefore, the donor pool could be expanded for any given patient. M-mode echocardiographic measurements of left and right ventricular internal dimensions, left ventricular mass, and percent fractional shortening were reviewed in 235 normal adult subjects (101 men, 134 women). Low correlation coefficients and a high degree of variance were consistently observed between cardiac parameters and body size. There were no significant differences in left ventricular internal dimension when women weighing 40 to 109 kg were compared with men statistically different among men weighing 50 to 99 kg. No difference was noted in right ventricular size among men and women. Echocardiography is a simple and accurate technique to assess cardiac dimensions. Body weight does not correlate well with adult cardiac size and should not be used as an exclusion criterion for a donor heart. PMID- 1755676 TI - First successful bridge to cardiac transplantation using direct mechanical ventricular actuation. AB - Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patient's native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under utilized method of total circulatory support. PMID- 1755677 TI - Mitral valve repair for ischemic mitral insufficiency. AB - Over a 5-year period, 1,292 patients had operation on their native mitral valves. Ischemia was the cause of mitral insufficiency in 84 patients (6.5%). Sixty-five patients (77.4%) had mitral valve repair. Mean age was 66 +/- 10 years; 35 patients (53.8%) were women. Mean degree of preoperative insufficiency was 3.2 +/ 0.7; mean preoperative New York Heart Association functional class was 3.3 +/- 0.7. Eleven patients (16.9%) had acute and 54 (83.1%) had chronic mitral insufficiency. Valve prolapse was present in 26 patients (40%). Restrictive leaflet motion secondary to regional or global left ventricular dilatation occurred in 39 patients (60%). All patients had associated myocardial revascularization followed by transatrial valvuloplasty. Multiple techniques were employed to achieve valve competence: leaflet resection (3), chordal shortening (15), papillary muscle reimplantation (10), papillary muscle shortening (3), and annuloplasty (63). There were six (9.2%) hospital deaths (acute, 9.1%; chronic, 9.3% [not significant]; prolapse, 11.5%; restrictive, 7.7% [not significant]). The mean degree of postoperative mitral insufficiency was 0.6 +/- 0.8 in 51 patients. At a mean follow-up of 3.1 +/- 1.6 years, patient survival was 96% for patients with valve prolapse and 48% for those with restrictive leaflet motion (p = 0.02). New York Heart Association functional class was improved in all groups. Ischemic mitral insufficiency is an uncommon cause of mitral valve disease that is amenable to repair in the majority of cases of both acute and chronic onset. The operative mortality is low, and operation is associated with superior survival in patients with valve prolapse. PMID- 1755678 TI - Bronchopleural fistula after stapled closure of bronchus. AB - The incidence of bronchopleural fistula after stapling among 2,243 pulmonary resections at the Rush-Presbyterian-St. Luke's Medical Center has been reviewed. There were 35 fistulas in 1,773 stapled and in 470 sutured bronchi (segmentectomy, 2; lobectomy, 1; bilobectomy, 9; and pneumonectomy, 23). We have found that the stapler is expedient and simple to use, and that it produces a hermetic and uniform closure. The stapler is contraindicated when the bronchus is thickened, inflamed, or of insufficient length. The overall incidence of bronchopleural fistula was 1.6%. Approximately two thirds of the patients with bronchopleural fistula had preoperative radiation therapy or chemotherapy or both. PMID- 1755679 TI - Bilateral latissimus dorsi cardiomyoplasty. AB - This study was undertaken to test the hypothesis that a bilateral latissimus dorsi cardiomyoplasty provides greater hemodynamic augmentation than a unilateral procedure. Two types of bilateral procedure and a left posterior cardiomyoplasty were tested in each of 8 mongrel dogs. R-wave synchronous muscle pacing was achieved with a programmable burst stimulator. Hemodynamic variables of stimulated beats were compared with those of a nonstimulated baseline using paired t tests. The effects of a double anterior muscle wrap were equal to a right anterior/left posterior configuration. Therefore, the data on the two types of bilateral procedure were combined and compared with the left wrap. Stimulation of the bilateral cardiomyoplasty resulted in significant increases in right ventricular pressure (44 +/- 3.1 versus 26 +/- 1.8), first derivative of right ventricular pressure (595 +/- 117 versus 196 +/- 14), pulmonary artery pressure (34 +/- 1.9 versus 23 +/- 1.6), left ventricular pressure (90 +/- 5.9 versus 69 +/- 5.3), first derivative of left ventricular pressure (1454 +/- 141 versus 1072 +/- 107), aortic pressure (80 +/- 5.4 versus 67 +/- 4.9), and peak aortic flow (9.4 +/- 1.1 versus 7.7 +/- 0.8) (p less than 0.05). Significant increases in all of these variables also occurred with stimulation of the left cardiomyoplasty, but the increases in right ventricular pressure, first derivative of right ventricular pressure, pulmonary artery pressure, and aortic pressure were larger for the bilateral than the left cardiomyoplasty. The bilateral and the left procedure can each augment systolic ventricular function. The bilateral procedure appears to have greater effects, especially on right ventricular function. PMID- 1755680 TI - Main bronchial sleeve resection with pulmonary conservation. AB - Twenty-seven main bronchial resections (19 left, 8 right) were performed without pulmonary resection between 1975 and 1991. The patients were 17 men and 9 women with an average age of 35 years (range, 20 to 65 years). Tumors comprised 55% of the lesions, including 9 carcinoid tumors (33%), 2 mucoepidermoid tumors, 2 fibrous histiocytomas, 1 hemangiopericytoma, and 1 large cell carcinoma. Scarring and stenosis secondary to multiple causes occurred in 10 patients (37%). Two patients had miscellaneous lesions. Presenting symptoms included dyspnea (52%), wheezing or stridor (44%), cough (41%), hemoptysis (37%), and pneumonia (18%). Preoperative chest roentgenogram was abnormal in 60% of patients, whereas tomograms delineated the lesion in 94%. All patients had bronchoscopy for lesion evaluation. Anesthesia was accomplished through a long single-lumen endotracheal tube in 19 cases and a double-lumen tube in 8 cases. Mobilization and exposure techniques to create a tension-free anastomosis were critical for left main bronchial resections and included pretracheal mobilization (100%), neck flexion (100%), tracheal and main bronchial retraction (85%), aortic and pulmonary artery retraction (44%), and intrapericardial hilar release (33%). All resections were for cure; there was no operative mortality. Morbidity in 4 patients (15%) included an anastomotic stenosis (successfully reresected), prolonged air leak and pneumonia, transient recurrent nerve palsy, and atelectasis. Median 5-year follow-up revealed 92% of patients alive, with only one of two late deaths being disease-related. Main bronchial resection is an ideal technique for selected benign and malignant lesions, allowing complete pulmonary parenchymal preservation. PMID- 1755681 TI - Treatment of aortic coarctation by axillofemoral bypass grafting in the high-risk patient. AB - Operative correction of coarctation of the aorta has been performed for 45 years. Reoperation for recurrent coarctation is necessary in as many as 5% to 10% of patients. Repair of recurrent coarctation carries an operative mortality of between 5% and 10%. Coarctation repair involves an increased risk in patients with advanced age, recurrent coarctation, congestive heart failure, and pulmonary disease. We report 3 cases where axillofemoral bypass has been used to treat high risk patients with aortic coarctation. Two patients had had previous coarctation repair in addition to serious medical problems. Another patient had suffered three myocardial infarctions and had disabling congestive heart failure. All patients had an immediate marked decrease in their preoperative peak systolic pressure gradient across the coarctation. Systemic hypertension and symptoms of congestive heart failure were improved in all patients. The length of follow-up was 15 months, 8.5 years, and 10.5 years. Reassessment with noninvasive vascular segmental pressure studies with and without an exercise component showed no recurrence of the pressure gradient. This procedure should be considered when treating coarctation of the aorta in the high-risk adult. PMID- 1755682 TI - Anomalous origin of the right pulmonary artery from the ascending aorta. AB - Five cases of anomalous origin of the right pulmonary artery from the ascending aorta were seen at our hospital. Patients 1 and 2 had an intact right pulmonary artery originating from a right posterior aspect (proximal form), and primary anastomosis of the right pulmonary artery and main pulmonary trunk was performed. Patients 3 and 4 showed a narrowing right pulmonary artery originating from near the base of the innominate artery (distal form). The stenotic right pulmonary artery was reconstructed with an 8-mm graft in patient 3, whereas patient 4 became inoperable because complete obstruction had developed in the right pulmonary artery during the 3 months that the patient was waiting to undergo operation. In patient 5, primary anastomosis was undertaken, but morphologically the anomalous origin was of the distal form, so the occurrence of stenosis in the reconstructed right pulmonary artery was a matter of concern. The morphological type was found to be related to the surgical options in this anomaly. Therefore, primary anastomosis was considered the best choice for a correction of the proximal form, whereas a graft interposition with a resection of the stenotic portion on the right pulmonary artery was deemed preferable in the distal form. PMID- 1755683 TI - Denervation of transplanted porcine lung causes airway obstruction. AB - Lung transplantation can be complicated by a form of small airway obstruction known as bronchiolitis obliterans. We tested the hypothesis that lung denervation causes small airway obstruction in young pigs (10 +/- 1 weeks). Control pigs had an innervated native lobe, and study pigs had either a denervated native lobe or a denervated transplant lobe. Transplanted pigs received standard immunosuppression. At 10 weeks we measured isolated left lobe pulmonary mechanics. Dynamic resistance in both study groups was significantly higher than in the lobectomy group, whereas dynamic compliance in both study groups was significantly lower than in the lobectomy group. No significant difference in resistance or compliance was noted between the transplant and reimplant groups. Histologic changes consistent with rejection were noted in the transplant lobes. We conclude that the small airway obstruction noted in this model is due to operative denervation rather than to immunosuppression or rejection. PMID- 1755684 TI - Cardioprotective effects of nucleoside transport inhibition in rabbit hearts. AB - The cardioprotective effects of a nucleoside transport inhibitor, R75231, were investigated in the isolated rabbit heart. The hearts were subjected to 20 minutes of global normothermic ischemia followed by reperfusion. Before ischemia either solvent (group 1), 5 mumol/L of adenosine (group 2), or 0.64 mg/L R75231 (group 3) was added to the perfusate. Preischemic hemodynamics were not changed by treatment, except for an increase in coronary flow in the adenosine group (126% of control; p less than 0.05). Upon reperfusion, coronary flow was depressed in the controls (72% of the preischemic control values), increased in the adenosine group (113%) and unchanged in the R75231 group (89%). Functional recovery was significantly better in the adenosine group as well as in the R75231 group as compared with the controls (p less than 0.05). Cardiac output was 74% of the preischemic control value in the R75231 group, 67% in the adenosine group, and only 38% in the controls. Analysis of the coronary effluent after reperfusion showed a significant inhibition of rapid release of purines and a reverse of the adenosine/inosine ratio in the R75231 group as compared with the others. We conclude that R75231 has a cardioprotective effect that is probably related to accumulation of endogenous adenosine. PMID- 1755685 TI - Transesophageal echocardiography in patients with mechanical circulatory assistance. AB - Transesophageal echocardiography was used to assess myocardial function and to detect complications after mechanical circulatory support for 8 patients with cardiogenic shock. In 3 of 8 patients, serial transesophageal echocardiography documented improvement of systolic ventricular function, and it was possible to wean these 3 patients from the ventricular assist device. In all patients, transesophageal echocardiography added clinically important information including the extent of left and right ventricular dysfunction (6 patients), presence of atrial or ventricular thrombus (5 patients), presence of pericardial effusion or clot (2 patients), and verification of the position of the intravascular device (1 patient). Thus, transesophageal echocardiography may provide clinically useful information regarding both the underlying cardiac disease and potential complications from the mechanical circulatory assistance. PMID- 1755686 TI - Vascular reactivity of human internal mammary and gastroepiploic arteries. AB - Patency rates of bypass graft conduits are thought to be influenced by the determinants of vascular tone. This study has comparatively examined the response of the human internal mammary and gastroepiploic arteries to potassium, noradrenaline, dopamine, 5-hydroxytryptamine, thromboxane, and histamine. The response to potassium was significantly greater in the gastroepiploic artery (Emax = 79.5 +/- 9.6 mN) than in the internal mammary artery (Emax = 27.0 +/- 6.4 mN). Dose-related constrictions were observed in both vessels to all agonists except histamine, which was ineffective in the gastroepiploic artery. Noradrenaline and dopamine produced comparable dose-related constrictions in each vessel, with similar EC50 and Emax (expressed as a percentage of potassium response) values, but 5-hydroxytryptamine (Emax, gastroepiploic = 10.8% +/- 1.9%; internal mammary = 71.8% +/- 21.2%) and thromboxane (Emax, gastroepiploic = 116.7% +/- 4.0%; internal mammary = 169.6% +/- 19.4%) were more efficacious in their constriction of the mammary artery; the potencies were similar. We conclude that there is a heterogeneity of response to some vasoconstrictors between the human internal mammary and gastroepiploic arteries. The internal mammary artery may be more predisposed to events that initiate vasospastic disorders. PMID- 1755687 TI - Tricuspid valve myxoma: a rare indication for tricuspid valve repair. AB - Excision of a myxoma involving the tricuspid valve often necessitates tricuspid valve replacement or a less than optimal margin of resection. We report a successful tricuspid valve repair after en bloc resection of a myxoma involving the septal leaflet of the tricuspid valve. PMID- 1755688 TI - Contralateral pneumonectomy after single-lung transplantation for emphysema. AB - An intractable contralateral air leak developed in a 46-year-old woman after right single-lung transplantation for emphysema. A left pneumonectomy was performed on postoperative day 17, leaving the patient with only one transplanted lung. Fifteen months postoperatively the patient is well and has satisfactory pulmonary function. Survival with a good quality of life is possible after single lung transplantation and bilateral sequential pneumonectomies. PMID- 1755689 TI - Aplasia of the right aortic cusp in a neonate: a life-threatening but curable anomaly. AB - A case of absent right aortic cusp causing serious aortic incompetence in a neonate is reported. A "bicuspidalization" repair broke down within 24 hours, but reoperation with annular enlargement and insertion of a 19-mm prosthetic valve resulted in complete recovery. This rare but life-threatening anomaly of the aortic valve can be recognized with Doppler echocardiography. Valve replacement in conjunction with aortic annular enlargement should be performed as primary repair. PMID- 1755690 TI - Extended aortic and left main coronary angioplasty with a single pericardial patch in a patient with Williams syndrome. AB - In a 9-year-old girl with supravalvular aortic stenosis combined with severe left main coronary artery trunk obstruction (Williams syndrome), the repair for both lesions was performed successfully by simultaneous extended aortoplasty and direct coronary angioplasty using a single double-flanged pericardial patch. PMID- 1755691 TI - Vagal schwannoma involving esophagus. AB - A rare case of vagal schwannoma (neurilemoma) with involvement of the distal esophagus is presented. Chronic progressive dysphagia was the only complaint related to the schwannoma. Barium swallow showed narrowing of the distal esophagus. The tumor was embedded in the wall of the esophagus. After biopsy and diagnosis of benign schwannoma, it was dissected from the esophageal muscle and mucosa. Diagnosis of benign schwannoma should be made before excision of the lesion to avoid an unnecessary esophagectomy. PMID- 1755692 TI - Use of a pericardial patch to bridge the conduction tissue during tricuspid valve replacement. AB - Tricuspid valve replacement carries a risk of causing complete heart block. To reduce this risk, a technique was developed to bridge the conduction system during prosthetic valve insertion in the tricuspid position. This technique, in which a pericardial patch is used to bridge the triangle of Koch, was performed successfully in 4 patients who underwent tricuspid valve replacement for Ebstein's anomaly of the tricuspid valve. PMID- 1755693 TI - Cosmetic approach for placement of the automatic implantable cardioverter defibrillator in young women. AB - A surgical approach is described for a more cosmetically acceptable placement of the automatic implantable cardioverter-defibrillator in young women. The transvenous sensing lead and the vena caval spring electrode are placed through a small subclavicular incision. The left ventricular patch electrode is placed through an anterior minithoracotomy in the crease under the left breast. A small transverse incision in the left lower quadrant is used to place the generator under the external oblique fascia in the low abdominal wall. Minimal cosmetic impairment from incisions and hardware results. PMID- 1755694 TI - Subclavian vein-to-right atrial bypass for symptomatic venous hypertension. AB - A new surgical technique for bypassing subclavian vein thromboses in patients undergoing hemodialysis is presented. Subclavian vein stenosis or occlusion can occur after the use of temporary access catheters in subclavian vein dialysis. If this occurs in a patient with an arteriovenous access fistula of an ipsilateral upper extremity, venous hypertension, massive edema of the arm, and dysfunction of the access graft may result. In 2 patients with this condition, we successfully performed axillary vein-to-right atrial bypass, which resolved swelling and restored function of the access graft. This may be an appropriate surgical option for symptomatic venous hypertension in such patients. PMID- 1755695 TI - Replacement of the aortic valve with a pulmonary autograft: the "switch" operation. AB - The transfer of the patient's own pulmonary valve to the aortic position developed from our earlier work with aortic homografts. The valve shows no progressive tissue failure and offers the prospect of a permanent valve replacement for young people. Like homografts, the valves can be inserted in the subcoronary position or as a root replacement. In infants and growing children root replacement should be used to benefit from the valve's growth potential. PMID- 1755696 TI - Thoracoplasty: the how and the why. PMID- 1755697 TI - Blood cardioplegia: a review and comparison with crystalloid cardioplegia. AB - The Oxford International Symposium on myocardial preservation provided an appropriate milestone and impetus to survey one aspect of operative myocardial preservation, namely blood cardioplegia, and to contrast it with the more popular crystalloid cardioplegia. This review is by no means complete or exhaustive but represents my best effort to summarize important information that has accumulated in the literature as blood cardioplegia, and our understanding of it, has evolved. It is appropriate to compare blood and crystalloid cardioplegia with respect to biochemical and physiological differences. Clinical comparison has been limited, for the most part, to randomized studies, and a number of differences and details of clinical management of the two techniques have been omitted, either because they seemed unimportant or there was no good information that would allow an objective comparison of their significance. Hopefully, the reader will recognize the intent to focus on meaningful differences and similarities between the two techniques and to present them fairly. PMID- 1755698 TI - Tetralogy of Fallot. PMID- 1755699 TI - Spontaneous esophageal rupture. PMID- 1755700 TI - Retrograde disc escape in a Harken mitral valve prosthesis 21 years after implantation. PMID- 1755701 TI - Vagal schwannoma. PMID- 1755702 TI - [Cytomorphological and cultural characteristics of tylosin-producing strains with different antibiotic activity]. AB - Cytomorphological and cultural characteristics of highly and low active collection strains of Streptomyces fradiae producing tylosin were studied. The strains were grown on agarized and liquid media. It was shown that unlike the low active strain, the highly active one was less sporogenic, the difference being more pronounced when tylosin was added to the agarized medium. When the strains were grown in the fermentation medium there were detected differences between them in the growth type and microcolony structure at the early stages of the fermentation process. During intensive synthesis of tylosin spheric structures were found to form near the hyphal surfaces. The phenomenon was previously observed in cultures producing other antibiotics. In the low active strain the structures were single while in the highly active strain they formed in large numbers. PMID- 1755703 TI - [Spectrophotometric analysis of tetracycline hydrochloride in the presence of thiamine bromide and riboflavin]. AB - Spectrophotometric determination of tetracycline hydrochloride concentrations in the presence of thiamine bromide and riboflavin at a light absorption wave length of 300 nm was shown possible. When the ratio of tetracycline hydrochloride and the total of thiamine bromide and riboflavin (w/w) was at least 10:1 the error of the method was less than 2 per cent. The procedure is useful in quality control of the dosage forms. PMID- 1755704 TI - [Stabilization of standard samples of levorin and nystatin with antioxidants]. AB - To prolong the storage period of the reference samples of levorin and nystatin, polyenic macrolide antibiotics, their effect of 23 antioxidants was studied by using rapid inactivation. The antioxidants belonged to compounds of different classes. The inactivation was performed at 20, 37 and 50 degrees C in the presence of 1, 2 or 5 per cent of the antioxidants. An antioxidant of the class of partially hydrated oxyquinolines was shown to have the highest stabilizing action on levorin and nystatin. It may be recommended for stabilizing the levorin and nystatin reference samples. PMID- 1755705 TI - [Obtaining human recombinant (serine-17) beta-interferon by the method of oligonucleotide-directed mutagenesis and its expression in Escherichia coli]. AB - The gene of human mutant (serine-17) fibroblast interferon was isolated with the use of highly efficient oligonucleotide-directed mutagenesis. On the basis of the constructed expression plasmid pPR-IFN Ser17 a strain producing human mutant beta interferon (VKPM V-4678) was developed. It was shown that the specific activity of the human mutant (serine-17) fibroblast interferon was 1 order of magnitude higher than that of the recombinant interferon which reaches the specific activity of natural fibroblast interferon. PMID- 1755706 TI - [Immunological study of lysates from the cell wall of group A Streptococcus]. AB - The chemical composition and presence of immunogenic components in the lysates of the cell walls of group A Streptococcus, type M29, were studied. The lysates were prepared with the use of muramidase. Fc-Receptors were detected in the lysates. Within the first 30 minutes of cell wall lysis by muramidase, 4 times higher amounts of the protein reacting with fibrinogen excreted than in the subsequent 4 hours. The lysates contained immunogenic proteins. Fraction III isolated by chromatography of the 30-minute lysate on DEAE-trisacryl formed a single precipitation band with lysate antiserum. The lysate Fraction IV forming three precipitation bands contained a protein not specific of the type. The protein was identical to the protein antigen from Triton X-100 extracts of group A Streptococcus, types M1, M12 and M29. The group-specific polysaccharide was detected in the lysate Fraction I and Fraction II of the 4-hour lysate. PMID- 1755707 TI - [Selection of the optimal conditions for the procurement and regeneration of protoplasts of the industrial strain of Streptomyces rimosus, the producer of oxytetracycline, and the effect of the protoplasting process on the antibiotic activity]. AB - Optimal conditions for protoplasting of the Streptomyces rimosus industrial strain No. 1 producing oxytetracycline were developed. Observation of the early stages of the protoplast regeneration in microchambers showed that there were two regeneration types: normal and anomalous. The latter was likely defined by the glycine effect on cell wall synthesis. It was accompanied by the stage in which the protoplasts had the form of multiplying protoplast-like cells. The protoplasting of the S. rimosus culture producing oxytetracycline resulted in an increase in the variability of an antibiotic producing property and the frequency of low active variants. PMID- 1755708 TI - [Immunomodulating properties of pectin from seawater grass Zostera]. AB - Immunomodulating activity of zosterin was studied. Zosterin is a pectin from sea grass belonging to Zostera with pronounced antibacterial activity and therapeutic efficacy in experimental infections. It was shown that parenteral administration of the drug 24 hours before the antigenic irritation stimulated the humoral and cellular immunity in F1 (CBA X C 57 BL/6) mice: an increase in the number of the antibody cells in the spleen, the DTH and the index of the splenocyte spontaneous proliferation. In the animals treated with injections of zosterin and infected intraperitoneally with a virulent strain of S. enteritidis there was observed a marked increase in migration of polymorphonuclear leukocytes to the abdominal cavity accompanied by an increase in their phagocytic activity. The results suggested the possible use of zosterin as a drug with associated antibacterial and immunomodulating activities. PMID- 1755709 TI - [Antimicrobial activity of piperacillin in vitro]. AB - There was an increase in the resistance of clinical isolates to piperacillin as compared to that in 1987-1988. It was shown on the kinetic models that there was difference in the effect of the inhibitory and subinhibitory concentrations of the drug on microorganisms in various growth phases. No post-antibiotic action against Staphylococcus aureus and Pseudomonas aeruginosa and a slightly pronounced dose-dependent effect with respect to Escherichia coli were noted. PMID- 1755710 TI - [Mathematical modeling of ampicillin pharmacokinetics in patients with altered excretory function of the kidneys]. AB - A physiological model of ampicillin pharmacokinetics in man is proposed. Its design stems from the data characterizing the antibiotic distribution in rats. The model is useful in describing the pharmacokinetics of ampicillin after its intravenous and intramuscular administration. An adequate description of the antibiotic distribution in blood suggested an agreement with the real values of the estimated antibiotic concentrations in the tissues. The concentrations of ampicillin and sulbactam in the tissues after their intramuscular combined administration in doses of 1 and 0.5 g, respectively, were compared. The physiological model of the pharmacokinetics was applied to evaluation of a possible interval in changing of the antibiotic half-life. There was analytical relationship between the ampicillin half-life and efficiency of the renal function. PMID- 1755711 TI - [Experimental and clinical data on the combined use of novocaine salt of benzylpenicillin and proteolytic enzymes]. PMID- 1755712 TI - [Biochemical activity of microbial populations of the gastrointestinal tract and the effect of antibacterial drugs]. PMID- 1755713 TI - [Microecology of the skin and its changes after administration of antibiotics]. PMID- 1755714 TI - [Various methodological approaches in controlled screening of antibiotic producers among the group of Coryneform bacteria]. AB - A methodical system for directed screening of cultures producing broad-spectrum antibiotics among soil saprophytic coryneform bacteria was developed. To isolate such cultures, it was recommended to use the glucose-yeast medium supplemented with malt extract (No. 18/3) and soybean-glucose medium with sodium sulfate and cobalt chloride (No. 20/3). The preliminary alkaline treatment of the soil substrates and the use of acidic soil samples were found to favour isolation of the Mycobacterium type cultures. It was recommended to use gram-negative tests microbes with relatively low antibiotic resistance for screening cultures producing broad spectrum antibiotics. Various agarized and liquid fermentation media were compared in regard to detection of antibiotic activity in the soil coryneform bacteria. The corn medium supplemented with protein-vitamin concentrate, glucose, lactose and starch (No. 116) proved to be the most efficient. PMID- 1755715 TI - Labeling drop bottles to avoid medication errors. PMID- 1755716 TI - Ocular injuries caused by elastic cords. PMID- 1755717 TI - Suture removal after blepharoplasty. PMID- 1755718 TI - An inexpensive, pressure-regulated air pump for fluid-air exchange during pars plana vitrectomy. PMID- 1755719 TI - Retinal pigment epithelial tears through the fovea with preservation of good visual acuity. PMID- 1755720 TI - Discoloration of a silicone intraocular lens 6 weeks after surgery. PMID- 1755721 TI - Comments on silicone intraocular lens discoloration. PMID- 1755722 TI - Secondary glaucoma and uveitis associated with Orcolon. PMID- 1755723 TI - Magnetic resonance imaging of eyelid springs and gold weights. PMID- 1755724 TI - Endophthalmitis associated with sutureless cataract surgery. PMID- 1755725 TI - Horner's syndrome secondary to spontaneous carotid dissection with normal angiographic findings. PMID- 1755726 TI - Primary aspergillosis of the orbital apex. PMID- 1755727 TI - Eyelid pain after magnetic resonance imaging-induced palpebral spring vibration. PMID- 1755728 TI - Behavior offset is rejected by organized medicine. PMID- 1755729 TI - When considering Oculinum (botulinum toxin type A) injection for the treatment of strabismus, can the surgeon anticipate different results in patients who have had previous strabismus surgery? PMID- 1755730 TI - Is the ophthalmologist as a clinician-scientist still viable? PMID- 1755731 TI - The use of the 193-nm excimer laser for myopic photorefractive keratectomy in sighted eyes. A multicenter study. AB - Photorefractive keratectomy was performed at three centers using the 193-nm excimer laser on 31 sighted myopic eyes. Preoperative refractive errors (spherical equivalent) ranged from -12.00 to -4.00 diopters (D) (mean, -6.49 +/- 1.75 D). Peribulbar anesthesia, a 5.2- to 6.0-mm beam diameter, and topical corticosteroids were used for up to 6 months after surgery. The epithelium healed within 3 to 4 days, and all patients returned to their best corrected visual acuity within 1 line of their preoperative acuity. There was minimal subepithelial reticular haze, peaking at 3 weeks and diminishing over the next 3 to 4 months, which was not felt to be visually significant. At 6 months, the average residual refractive error was -1.85 +/- 2.5 D. Sixty-eight percent of eyes were corrected within 2 D and 55% within 1 D of attempted correction. There was no significant change in astigmatism, contrast sensitivity, corneal sensation, or endothelial cell counts. This preliminary work shows that photorefractive keratectomy has promise in the reduction of moderate myopia. PMID- 1755732 TI - Surface ultrastructure after excimer laser ablation. Expanding vs contracting apertures. AB - Excimer laser corneal ablation (photorefractive keratectomy) for myopia using a diaphragm delivery system was performed on eye bank and animal eyes by either progressively expanding or contracting the iris aperture. Use of an expanding aperture, in which the final ablations cover the entire treatment zone, produced a pseudomembrane over the zone that had few discontinuities. Ultrastructural examination of the corneas ablated using a progressively contracting aperture, however, revealed numerous discontinuities in the surface pseudomembrane. Use of an expanding iris aperture to perform ablations to correct myopia may be preferable as it produces a pseudomembrane with few discontinuities. Clinical studies of surface healing in humans are necessary to determine the clinical relevance of improved continuity of the surface pseudomembrane. PMID- 1755733 TI - Energy levels and probe placement in contact transscleral semiconductor diode laser cyclophotocoagulation in human cadaver eyes. AB - We investigated the effects of semiconductor diode laser contact transscleral cyclophotocoagulation in human cadaver eyes by gross examination, light microscopy, and scanning electron microscopy to determine optimum clinical treatment parameters. Irradiation was performed using a continuous-wave semiconductor diode laser with a fiber-optic probe. At 1.0 to 1.25 mm posterior to the limbus, spots were centered on the pars plicata by gross examination. Exposures of less than 2 J produced no visible damage. A 2- to 3-J exposure produced mild whitening of the ciliary processes, while 4- to 5-J exposures created more intense whitening of the pars plicata. Energies higher than 5 J frequently produced explosive tissue damage. Light microscopy of tissue treated with 1.8 to 6 J at 1.0 to 1.25 mm posterior to the limbus revealed coagulation necrosis of the nonpigmented and pigmented epithelium, with evidence of thermal coagulation of the ciliary stroma and stromal vasculature. Coagulation necrosis was more intense with longer exposure times. We found the optimum parameters for contact transscleral diode laser cyclophotocoagulation in cadaver eyes to be 3 to 4.5 J of energy delivered with the anterior edge of the probe 1.0 to 1.25 mm posterior to the limbus. PMID- 1755734 TI - Gyrate atrophy of the choroid and retina. Long-term reduction of ornithine slows retinal degeneration. AB - Gyrate atrophy of the choroid and retina is an autosomal recessive, chorioretinal dystrophy that begins in childhood and leads to blindness in the fourth to seventh decade of life. The primary defect is deficiency of ornithine-delta-amino transferase, which results in accumulation of ornithine. We examined six pairs of affected siblings to determine if intrafamilial variability in the phenotype was less than interfamilial, and to determine if long-term (5- to 7-year) reduction of ornithine with an arginine-restricted diet had an effect on the progression of the chorioretinal degeneration. All but one set of siblings underwent periodic ophthalmologic examinations. The clinical diagnosis was confirmed with the demonstration of hyperornithinemia and deficiency of ornithine-delta aminotransferase. The molecular defects in their ornithine-delta-amino transferase genes also were determined. The two younger pairs of siblings were given an arginine-restricted diet and followed up for 5 to 7 years. We found strikingly similar phenotypes in affected members of the same pair of siblings. In the young patients receiving the diet, there was substantial reduction of ornithine levels. These children had only modest progression of their ocular disease during this period. Furthermore, a comparison of the outcome of the younger with their older siblings at an equivalent age showed that the younger siblings, who started receiving the diet at an earlier age, had much less ocular disease. We conclude that intrafamilial phenotypic variation in gyrate atrophy is less than interfamilial and, therefore, that genetic heterogeneity plays a role in the phenotypic variability of gyrate atrophy. Furthermore, we conclude that chronic reduction of ornithine with an arginine-restricted diet dramatically slows the progression of the chorioretinal dystrophy. PMID- 1755735 TI - Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. AB - Laser photocoagulation in a grid pattern is effective in many eyes in resolving diffuse diabetic macular edema and stabilizing vision. We retrospectively studied 203 eyes of 203 patients, all of whom had diabetic macular edema treated with grid laser photocoagulation. During the follow-up period, 11 of these 203 eyes developed enlargement of the laser scars that progressed into the central fovea. Each of the 11 eyes experienced loss of vision, and in five, the visual loss was significant. Five of these eyes also developed a retinal pigment hyperplastic scar. After the laser treatment, but before the scars enlarged, the visual acuity of these eyes was unchanged from that before treatment. But after the atrophic scars enlarged into the central fovea, visual acuity in one eye decreased from 20/40 to 20/100, and the other 10 eyes had visual acuities of 20/200 or worse. PMID- 1755736 TI - Familial aggressive nevi of the iris in childhood. AB - We report the occurrence of amelanotic melanocytic tumors of the iris arising in the second decade of life in two successive generations. Clinically, both tumors enlarged rapidly, with subsequent enucleation of the eye in one patient. In both cases, histologic examination revealed an aggressive iris nevus composed of spindle A cells. Both lesions had similar argyrophilic nucleolar organizing region counts, which may be of prognostic significance. A possible autosomal dominant pattern of inheritance for this rare tumor is discussed. PMID- 1755737 TI - Eyelid movements in facial paralysis. AB - We studied the eyelid movements of six patients with unilateral, isolated, facial paralysis using the magnetic search coil. The most significant abnormality consisted of a reduction in the magnitude of the orbicularis oculi contraction with slowing of the peak velocity of the closing phase of the blink. The closing phase blink velocity, which normally increases linearly as a function of amplitude (main sequence), in our patients displayed a relationship characterized by a slow saturating power function that fell off the main sequence. The contralateral normal lid in some cases can show adaptive signs of hyperactivity during the closing phase of the blink. Lid saccades showed a small but consistent decrease in amplitude and velocity compared with the contralateral unaffected eyelid. Unlike the closing phase of the blink, peak velocities of lid saccades stayed on the main sequence. In this study, we discuss how the eyelid executes downward lid saccades based purely on a passive mechanism. PMID- 1755738 TI - Infectious endophthalmitis following sutureless cataract surgery. AB - Within the last 6 months, three cases of infectious endophthalmitis following sutureless cataract surgery have been referred to us. Two of these cases followed uncomplicated sutureless phacoemulsification with intraocular lens implantation. One case was complicated by a postoperative hyphema with additional surgery for clot removal 2 days following the initial procedure. PMID- 1755739 TI - PhXA34, a new potent ocular hypotensive drug. A study on dose-response relationship and on aqueous humor dynamics in healthy volunteers. AB - The prostaglandin analogue PhXA34 was tested in two studies in normal human eyes; 1, 3, and 10 micrograms of PhXA34 reduced the intraocular pressure by about 2, 3, and 4 mm Hg, respectively, 6 to 10 hours after a single topical dose. The only side effect observed was a slight conjunctival hyperemia after 10 micrograms of PhXA34. In a second study we determined the effect of 10 micrograms of PhXA34 once daily for 7 days on intraocular pressure, outflow facility, aqueous flow, blood-aqueous barrier permeability, ocular discomfort, and hyperemia. The mean intraocular pressure was below 9 mm Hg 12 hours post dose. About one third of the intraocular pressure reduction could be explained by increased outflow facility. Aqueous flow was unaffected. Treatment caused a 21% increase in aqueous fluorescence 1 hour after an oral dose of fluorescein. Mild ocular discomfort and some hyperemia were initially observed in half of the subjects, but frequency and magnitude of these side effects declined during the study. PMID- 1755740 TI - Massive suprachoroidal hemorrhage with central retinal apposition. A clinical and echographic study. AB - We reviewed the charts of 18 patients diagnosed with a massive suprachoroidal hemorrhage (MSCH) with central retinal apposition (kissing configuration). Four cases occurred intraoperatively (expulsive), eight after a surgical procedure (delayed), and six associated with blunt or perforating injury (traumatic). In this study, echography was used to monitor the course of MSCH; the mean time for clot lysis was 14 days, and the mean duration of central retinal apposition was 15 days. The expulsive MSCHs were all allowed to resolve spontaneously, with good initial visual outcome in three of the four eyes in which they occurred. In the delayed MSCH group, the majority of patients attained their prehemorrhage visual acuity, with or without early surgical intervention. In the traumatic MSCH group, retinal detachment was a constant complication in all patients. All six patients in the traumatic MSCH group had a poor visual outcome, despite early surgical intervention in five patients. The results of this study suggest that not all MSCHs need to be drained surgically and that, when surgical drainage is indicated, echography may be a useful adjunct in determining the optimal time of drainage. PMID- 1755741 TI - Sinus histiocytosis involving the lacrimal sac and duct. A clinicopathologic case report. AB - A 17-year-old girl with right-sided epiphora and a lacrimal sac mass was found radiologically to have marked enlargement of her lacrimal sac and nasolacrimal duct and mucosal thickening of her right nasal turbinates and maxillary, ethmoid, and sphenoid sinuses. Biopsy specimens from all these sites showed chronic inflammatory infiltrates with a predominant population of large phagocytic histiocytes, some of which had engulfed lymphocytes and plasmacytes. The results of a systemic workup were normal. This is the first reported case, to our knowledge, of sinus histiocytosis involving the lacrimal sac and nasolacrimal duct as an extranodal focus. PMID- 1755742 TI - Eosinophil and neutrophil degranulation in ophthalmic lesions of Wegener's granulomatosis. AB - Although eosinophils and neutrophils have been identified in orbital and corneoscleral tissues in some patients with Wegener's granulomatosis, their role in the pathogenesis of the disorder is not completely understood. Nine specimens from six patients with Wegener's granulomatosis and autopsy controls from patients without ophthalmic disease were evaluated with indirect immunofluorescence for eosinophil granule major basic protein and neutrophil elastase. Extracellular deposition of both major basic protein and elastase was identified in orbital tissues from all the patients with Wegener's granulomatosis. Two of the specimens were from enucleated eyes with corneoscleral disease; extracellular deposition of eosinophil major basic protein was identified in one eye, and extracellular neutrophil elastase was deposited in both eyes in lesional areas. None of the control tissues showed major basic protein or elastase deposition. These findings suggest that both eosinophils and neutrophils participate in the pathogenesis of the orbital and corneoscleral manifestations of Wegener's granulomatosis. PMID- 1755743 TI - Early lesions of bilateral diffuse melanocytic proliferation. AB - The early lesions of bilateral diffuse melanocytic proliferation were studied with fluorescein angiography in a 63-year-old woman. We first observed a small choroidal melanoma in the left eye and several flat melanocytic lesions in both eyes. Extension and growth of new melanocytic lesions and leakage at the level of the pigment epithelium were then noted. Subsequently, pink patches, with an eye catching early hyperfluorescence, appeared in the posterior fundus in both eyes. The patient experienced progressive visual loss during the 8-month follow-up period before her death. Histopathologically, the uveal tracts were diffusely thickened by melanocytic proliferation. The primary systemic neoplasm was an ovarian carcinoma, found in five of 18 patients with this unusual paraneoplastic syndrome. PMID- 1755744 TI - Influence of corticosteroid on experimentally induced keratomycosis. AB - To assess the effect of corticosteroid on the establishment of experimentally induced keratomycoses, rabbits were injected subconjunctivally with triamcinolone acetonide on two successive days before inoculation with Candida albicans, Aspergillus fumigatus, or Fusarium solanae. Whereas isolate recovery rates declined steadily in normal control corneas, they remained stable over 15 days in corticosteroid-treated corneas. Clinically, inflammation was equivalent (A fumigatus and F solanae) or significantly less (C albicans; P = .001) until the 10th day. At 15 days, inflammation in corticosteroid-treated corneas was significantly worse in animals infected with A fumigatus (P = .003) or F solanae (P = .02). Inflammatory signs correlated inconsistently with isolate recovery. Pathogenicity of the infecting organism appears to be important in determining the degree to which corticosteroid is able to mask clinical signs of infection while enhancing fungal replication. PMID- 1755745 TI - Holmium-YAG laser surgery on experimental vitreous membranes. AB - We used a pulsed holmium-YAG laser that emitted in the midinfrared (2.12 microns) to cut experimental vitreous membranes in rabbits via an intraocular fiberoptic delivery system. Thirty-five membranes were treated at distances of 0.5 to 3.8 mm from the retina. All of the membranes that were treated were transected or partially cut. In cases that were treated with the optical fiber encased in a retinal-shielding pick, membranes could be readily transected without retinal injury. Laser vitreous membrane cutting may offer the advantage of near tractionless membrane segmentation. The combination of a moderately strong target tissue absorption and the ready availability of commercial optical fibers for transmission of 2.12-microns laser energy suggests that the holmium-YAG laser merits further investigation for this application. PMID- 1755746 TI - Palladium 103 ophthalmic plaque radiotherapy. AB - We compared the ocular radiation distribution of palladium 103 (103Pd) vs iodine 125 (125I) ophthalmic plaques sewn to 12 human donor eyes. We then performed preoperative comparative simulations on the first seven patients to be treated with palladium 103 plaque therapy for choroidal melanoma. The in vitro experiment involved palladium 103 seeds placed into a Silastic seed holder, which was affixed into standard 14-mm gold eye plaques. Then the plaques were sewn onto 12 human donor eyes so as to approximate either the nasal (six eyes) or temporal (six eyes) equator. Three sets of two thermoluminescent dosimeters were used to quantify the amount of radiation delivered by the episcleral plaques. Thermoluminescent dosimeters were sewn to the sclera in three locations: on the center of the cornea, on the sclera beneath the macula, and at the equator in a position opposite the plaque. This experiment was then repeated with iodine 125 seeds and thermoluminescent dosimeters. After the plaques were adjusted to equalize their activity (plaque strength), the palladium 103 plaques were found to deliver less radiation to the three target points. Comparative clinical dosimetry also reflected this difference. Preoperative simulations comparing equal doses to the tumors' apex revealed that the palladium 103 ophthalmic plaques delivered more radiation to the tumor and less radiation to most normal ocular structures. PMID- 1755747 TI - Conjunctival prolapse. PMID- 1755748 TI - Impairment, disability and handicap in audiology: towards a consensus. AB - Within this paper, we argue that the WHO definitions of impairment, disability and handicap have a useful role in understanding the processes of audiological rehabilitation. We have endeavoured to clarify some of the confusions arising from the various uses of the terms in the audiological literature and propose further classifications of the three. In particular we discuss the complexities of handicap together with the interactions between hearing-impaired individuals and their significant others in its production. PMID- 1755749 TI - Longitudinal study of changes in speech perception between 70 and 81 years of age. AB - As part of a large gerontological study in Goteborg, Sweden, 376 randomly selected men and women born in 1901-1902 underwent pure-tone and speech audiometry at the age of 70 years in 1971-1972. The survivors of the 1901-1902 cohort were tested again at the ages of 75, 79 and 81 years. A second group consisting of 297 men and women born in 1906 was also tested with pure-tone and speech audiometry at the ages of 70 and 75 years. We found that the median speech discrimination scores for the 1901-1902 cohort decreased moderately with increasing age: between the ages of 70 and 81 years scores decrease 10% for men and 8% for women for the worse ear and 7 and 6% for the better ear in this group. The median speech reception threshold increased 15 dB over the 11-year period for both men and women, an increase in good agreement with the increase in the pure tone threshold over this period. Those born in 1906 had a slightly lower discrimination score (4%) when tested at the age of 70 years compared to those born in 1901 tested at the same age. As many as half of the 81-year-old persons would have a theoretical benefit from hearing aid amplification. PMID- 1755750 TI - [Clinical study of speech understanding in noise]. AB - The goal of this study was to determine the extent to which the difficulty frequently experienced by hearing-impaired listeners in understanding noisy speech can be clinically described in terms of the auditory site of lesion. To this end, shifts of speech reception threshold in noise, using standardized franco-quebecois bisyllabic word lists, were obtained from noise-exposed workers and compared to Plomp's model to ascertain content validity. Shifts resulted from monaural listening to a broad-band speech spectrum noise held constant at 0 dB signal-to-noise ratio. In this manner, increasing the presentation levels of both speech and noise was expected to progressively minimize the contribution of Plomp's class A attenuation component to speech hearing loss and eventually show an unequivocal manifestation of its distortion component (class D speech hearing loss). Listeners were 457 noise-exposed workers giving a total of 914 observations. Rejection of those ears with suspected middle-ear pathology led to a reduction to a total of 709 observations representing various degrees of permanent hearing impairment. An additional 98 observations showed normal hearing sensitivity in spite of noise exposure averaging 9.6 years. Results indicated the presence of five categories of speech threshold shifts varying independently of hearing sensitivity. 59.8% of those observations with permanent hearing impairment (424/709) simultaneously showed a problem understanding speech in noise. On 78 occasions, listening in noise was so disturbed that the 50% performance level corresponding to the speech threshold could no longer be established within reasonable limits, that is up to 65 dB above the speech threshold in a quiet environment. Conversely, 26.5% of the observations with essentially normal hearing sensitivity (26/98) showed reduced speech reception in noise. Fitting Plomp's model confirmed our expectations for two of the five categories of scores. A principal component analysis identified similar behaviour of speech threshold shifts in noise compared with Plomp's class D speech hearing loss. Hence, these speech threshold shifts in noise were interpreted as predominantly reflecting peripheral auditory disorders, that is defective frequency selectivity and temporal resolution. The remaining categories were found to be under the predominant influence of two other mechanisms: (1) band width reduction resulting from impaired hearing; (2) disorders associated with certain non-auditory cognitive factors, namely selective attention and the ability to make use of the redundancy of the message. PMID- 1755751 TI - Application of phase-induced lateralization to the Stenger test. AB - The Stenger test was employed to estimate the genuine hearing thresholds in normally hearing volunteer subjects simulating a total unilateral loss. The test was carried out in its standard form and in a modified form in which a phase shift was introduced between the signal delivered to the two ears, set to produce phase-induced lateralization towards the 'poor' ear. The standard test estimated the thresholds at a mean of 13.5 dB above the true thresholds at five frequencies from 250 Hz to 4 kHz. Thresholds at the different frequencies were compared, and although thresholds were lower for the higher frequencies, the apparent effect of frequency was not statistically significant. The modified test, using a 90 degrees phase shift, was found to enhance the test at 250 and 500 Hz (thresholds estimated at about 7 dB above true values), but not significantly at 1 kHz. PMID- 1755752 TI - Primitive neuroectodermal tumour in the oral cavity. Case report. AB - Primitive neuroectodermal tumour is regarded as a rarely seen lesion as it occurs mainly within the central nervous system. However, this neoplasm does occasionally occur elsewhere in the body. One such case which occurred in the posterior part of the palate in a child is reported. Following a combined therapeutic approach comprising surgery, radiotherapy and chemotherapy, the patient has been well for nine years since treatment. PMID- 1755753 TI - The early development of palatal rugae in the rat. AB - The palatal rugae in rats are contained in two of three zones of morpho differentiation and develop around the time of palatal closure. Previous studies in humans and pigs have been based on crown-rump lengths but now controlled breeding in rats has allowed exact timing to be established. Twenty-nine female DB IX rats were fertilized and sacrificed in a controlled procedure and foetuses processed for light microscopy and SEM. Serial sagittal sections were made and stained with haematoxylin and eosin and Verhoef's stains. At day 13 the palate was open and no rugae were visible. At day 14 the palatal shelves had started to migrate medially and the ante-molar rugae appeared. At day 15 the palatal shelves were touching and the inter-molar rugae became visible, and at day 16 fusion was all but complete and the definitive rugal pattern established. The development and differentiation is more advanced than in humans and it is concluded that the rugae probably have a role to play in the oral function of animals whereas in humans they are becoming attenuated and the development timetable is retarded because of redundancy. PMID- 1755754 TI - Treatment planning in orthodontics and orthognathic surgery: the significance of tooth inclination and dental compensations. AB - The scope of orthodontic treatment is examined and the importance of the initial tooth inclinations and skeletal base relationships is explained. Dental compensations which occur in all three planes of space are discussed. Special attention is given to the importance of dental compensations in the antero posterior plane in orthognathic surgery treatment planning. There is a necessity for early definitive decision-making in the borderline orthognathic surgery patient and the role of orthodontic camouflage is pointed out. Case selection for treatment with removable appliances is explored. PMID- 1755755 TI - Cervical enamel projections in Chinese first permanent molars. AB - Cervical enamel projections in relation to molar furcations may act as predisposing factors in periodontal attachment loss. Limited data are available documenting these features in Chinese teeth. The purpose of this study was to determine the prevalence and distribution in a sample of first permanent molars from Hong Kong Chinese. Three hundred and sixty-two extracted first molars (194 maxillary, 168 mandibular) were selected from the Prince Philip Dental Hospital tooth collection and examined using a dissection microscope for identification and classification. Cervical enamel projections were identified in 59 per cent of maxillary and 79 per cent of mandibular first molars. Buccal aspects were more frequently involved. Forty-nine per cent were Grade III (extending to the furcation area); over one-half were particularly slender while 18 per cent were discontinuous. A modification to the classification system is proposed in order to delineate these features in future studies. PMID- 1755756 TI - Mandibular osteomyelitis and pathologic fracture associated with metabolic catabolism induced by 'binge' drinking. Case report. PMID- 1755757 TI - Bony lid approach for apicoectomy of mandibular molars. AB - Apicoectomy in the lower molar region is indicated in many instances to avoid the need for prosthetic appliances. Nevertheless it is a method sometimes rejected by oral surgeons because of the thickness of the buccal compact bone in the lower molar area leading to extensive bone loss in addition to a restriction of vision and access during the operation. The present study reports twenty-four cases of apicoectomized mandibular molars treated with the bony lid approach which facilitates considerably the apicoectomy procedure. Once part of the buccal compact bone in the periapical area of the molars is removed, favourable conditions are created for the completion of the operation under direct vision of the operational field. The replacement of the buccal compact bone then minimizes the dimensions of the remaining bone cavity. PMID- 1755758 TI - The hard tissue lesion revisited. AB - Recent research indicates that the thorough removal of calculus is still a critical step in the treatment of periodontal disease. Surgical access facilitates this in deep pockets. Repair is mediated by a long junctional epithelium as microscopically total calculus removal is rarely achieved. In intrabony defects the apical portion of the root surface which has not attracted deposits of calculus has the potential for connective tissue reattachment and regeneration if care is taken to preserve collagen fibres still attached to the root. PMID- 1755759 TI - A national survey of dentists' management of children with anxiety or behaviour problems. AB - Seven-hundred and sixty dentists, selected randomly from all States and Territories except Victoria, responded to a questionnaire survey on beliefs, attitudes and the techniques used in the management of children with anxiety or behaviour problems. The most common techniques used were permitting the child some degree of control over terminating treatment if difficulties were experienced, coaxing and reinforcing positive behaviours, and furnishing waiting areas with child-oriented play materials. Most respondents never used TV or video tape distraction strategies, film or video-modelling tape or hypnosis. More than half of the respondents believed there was insufficient information available to them on current anxiety/behaviour management techniques. The use of particular management techniques varied by gender, age, university of graduation, State or Territory of residence, and membership of the Australian and New Zealand Society of Paediatric Dentistry. Patterns of use of particular techniques showed similarities and contrasts with other studies. Patterns of use in the national sample were almost identical to the frequency and pattern of use by Victorian dentists. In contrast, however, North American studies have reported a higher frequency of use of hand-over-mouth, and lower use of general anaesthesia within the armamentarium of techniques and strategies used by dentists to manage anxious or difficult children. PMID- 1755760 TI - Dimensional accuracy of small gold alloy castings. Part 2. Gold alloy shrinkage. PMID- 1755761 TI - Large database management in clinical dental research. AB - Previously the management and analysis of large databases for longitudinal clinical dental research has been severely restricted by the costs of custom-made software and access to suitable computing equipment. However, the recent availability of powerful personal computers and the use of the Scientific Information Retrieval Database Management System (SIR/DBMS) in association with BMDP Statistical Software has now created an enormously powerful tool for extensive and fast data manipulation requiring relatively few commands and the capability to easily perform detailed statistical analyses. PMID- 1755762 TI - Treatment of facial disharmony and malocclusion by jaw surgery. PMID- 1755763 TI - Bruxism. PMID- 1755764 TI - Surgeons International. PMID- 1755765 TI - Recent changes in the Part II FRACS Examination. PMID- 1755766 TI - Are you wasting your time with journals? Some guidelines for selective reading. PMID- 1755767 TI - Preventing breast cancer: is it possible? AB - Breast cancer is a common cause of suffering and death in Australia. Improvements in detection and therapy will make only small inroads into mortality, and will not reduce suffering. Reducing the incidence of breast cancer by preventive measures is a logical step, and this paper reviews how it might be achieved. Reducing the population's exposure to known risk factors for breast cancer is logical; however, the potential for improvement is limited. Reduction in age at first pregnancy is impractical and measures such as weight reduction and reducing consumption of fat and alcohol are likely to be only partially successful. Increasing activity in youth is a concept that requires further investigation, but is a possible area of promise. Exogenous hormone use probably contributes little to the incidence of breast cancer, but prescribing patterns for post menopausal oestrogens are changing and require monitoring. The use of hormone manipulation to prevent breast cancer has considerable potential benefit. Two approaches have been proposed. The first involves reversible suppression of ovarian function by luteinizing hormone-releasing hormone (LHRH) agonists after child-bearing has finished, combined with low-dose conjugated equine oestrogen to compensate for oestrogen loss. The other involves the use of the anti-oestrogen, tamoxifen. Both measures have the potential to halve breast cancer incidence. There is some evidence that non-hormonal chemoprevention is possible, but clinical trial data are lacking. PMID- 1755768 TI - Breast cancer in the elderly: pattern of disease. AB - The elderly (aged 70 years or more) constituted 201 (37%) of 548 first-time admissions to a single institution for breast cancer between 1976 and 1985. The pattern of disease was studied and contrasted with that seen in younger patients (less than 70 years old). Currently, 5000 new breast cancers are diagnosed in Australia each year. It is projected that the proportion of new breast cancer patients who are elderly will rise from 37 to 60% by the year 2031. In general, the disease was similar to that seen in younger patients. Minor histological differences occurred and there were tendencies towards late presentation and clinically less aggressive disease. Tumour size, the presence of metastases and UICC staging were useful predictors of outcome but nodal status and hormone receptor levels did not discriminate. An unexpected finding was the relative longevity of elderly patients with breast cancer. The stage-specific 5-year survival rates (UICC stages: I--73%; II--65%; III--42%; IV--10%;) did not differ significantly from those seen in younger patients. PMID- 1755769 TI - Radical neck dissection in nasopharyngeal carcinoma. AB - We report a series of 37 patients who had radical neck dissection for residual or recurrent lymph node metastasis from nasopharyngeal carcinoma after radiotherapy. The operation was performed despite high doses of pre-operative radiotherapy. There was no operative mortality and the morbidity was 13% (2 prolonged chylous drainage, 3 sloughing of neck flap). The risk of sloughing of neck flap was significantly related to previous lymph node biopsy, which should be avoided if at all possible. In 35% of patients, the lymph node was densely adherent to neighbouring structures. In the 28 patients who had single lymph node clinically, 29% had multiple neck node involvement noted during operation; another 14% were documented only on histological examination. Radical neck dissection rather than excision alone is justified for the clinically solitary lymph node. PMID- 1755770 TI - Venous drainage of free flaps following radical neck dissection. AB - Large tissue defects may occur following head and neck surgery. When combined with ipsilateral radical neck dissection the venous drainage of a free flap used to cover the defect may be compromised. Twelve patients having radical neck dissections underwent on-table venography to study the pattern of venous drainage of these flaps. The predominant drainage pattern is initially in a cephalic direction, then across the midline and finally in a caudal direction on the contralateral side of the neck. Venous drainage to the contralateral side of the neck may be a determinant of flap survival. In order to facilitate venous drainage following free flap procedures, patients should be positioned so that the contralateral internal jugular vein is not compressed. Drains should be placed caudal to the microvascular anastomoses in order to minimize interference with the cephalic direction of venous drainage. Any patient having a radical neck dissection requiring a central venous catheter should have it placed ipsilateral to the neck dissection. Thrombosis around a contralaterally placed cannula may significantly increase head and neck venous pressure. PMID- 1755771 TI - Laser treatment of pharyngeal pouch. AB - The symptoms of pharyngeal pouch become more troublesome, eventually requiring surgical treatment. Excision of the pouch and cricopharyngeal myotomy through a neck incision was the operation of choice until Dohlman described endoscopic diathermy operative treatment 30 years ago. The diathermy technique has been largely superseded by endoscopic microsurgical division of the cricopharyngeus muscle in the party wall using carbon dioxide laser. This operation is now established as a precise, accurate and safe procedure providing reliable relief of symptoms with minimal risk to the patient. Fifteen patients treated by the microsurgical laser procedure in the past 5 years are reported. PMID- 1755772 TI - Canal wall down techniques for managing cholesteatoma. AB - Cholesteatoma remains a common otological problem. This series shows that a simple open cavity technique, with meatoplasty, remains a cost-effective option for treatment. Most ears are rendered dry and safe, with cavity problems minimized by careful technique. Subsequent outpatient care is required infrequently and is well tolerated. The hearing is no worse after the operation than before and some ears are suitable for subsequent tympanoplasty. PMID- 1755773 TI - CT-guided stereotactic neurosurgery using the Brown-Roberts-Wells system: experience with 125 procedures. AB - Experience with a consecutive series of 125 computerized tomographic (CT) image guided stereotaxic neurosurgical procedures, performed using the Brown-Roberts Wells (BRW) system is described. Operative objectives included tissue sampling for diagnostic purposes, intra-operative localization of craniotomy flaps and intracerebral lesions, cyst and abscess aspiration and lesion to modulate tremor. A neuropathological diagnosis was possible in 96% of the biopsies, and lesions were precisely localized in all patients undergoing microsurgical stereotaxic craniotomy. Two patients (2.2%) undergoing stereotaxic biopsy died as a result of the procedure and one patient's hemiparesis was permanently worsened (0.8%). In only one of three patients undergoing stereotaxic thalamotomy was tremor abolished. This report confirms that CT image guided stereotaxic neurosurgery is safe, accurate and versatile. There is, however, a moderate incidence (7.2%) of lesser complications that can occur with this type of surgery. These complications, which are emphasized in this paper, are related to both the site of surgery and the neuropathology. PMID- 1755774 TI - The hand in heraldry. AB - The display of hands in heraldry provides a graphic reminder of both the origins and development of medical institutions, and of certain aspects of the functional anatomy of the hand--aspects which are of importance to the surgeon who deals with the injured hand. The elegance of the hand appeals to surgeon and heraldic artist alike. PMID- 1755775 TI - Heparin reduces the intimal hyperplasia seen in microvascular vein grafts. AB - The influence of heparin on microvascular vein graft intimal hyperplasia was studied in a rat model. The iliolumbar vein was grafted into the iliac artery in 80 rats. Heparin was delivered via a subcutaneous miniosmotic pump, starting either 2 days before grafting (early heparin group, n = 20) or immediately after grafting (heparin group, n = 30). Saline-containing pumps were placed in the control group (n = 30). Heparin activity was measured at 24 h, and again 3 weeks later when the animals were sacrificed. The grafts were harvested and prepared for histological examination. The intimal thickness was measured at the anastomoses and in the mid-graft region using an eye-piece graticule set at right angles to the graft internal elastic lamina. Heparin significantly reduced the intimal thickness at the anastomoses, from a median of 38 microns (range: 10-100 microns) in the control group to a median of 20 microns (range: 10-150 microns) in the heparin group. A similar reduction was seen in the mid-graft region. Although intimal thickening was reduced in the early heparin group, this reduction failed to reach statistical significance. The possible clinical application is discussed. PMID- 1755776 TI - Pre- and post-testing of students in surgery: do medical rotations help? AB - A prospective multiple choice question (MCQ) study developed to pre- and post test fifth year medical students at the University of Queensland, was undertaken during 1990. We investigated whether there was a significant gain in their surgical knowledge base resulting from non-surgical rotations during the same year. We have previously reported a retrospective study suggesting that there was such a gain. Comparable clinical surgical pre- and post-tests were adapted from a fresh question bank, and were presented prospectively to four groups of fifth year medical students at the beginning and end of each 7 week General Surgical term. In contrast to our retrospective study, we found there was no significant increment in surgical knowledge using non-parametric Notched Box and Whisker Plot analysis of data. We conclude that this is either because students are compartmentalizing their factual knowledge base between one speciality and the next, or that indeed there is no benefit to Surgical knowledge base from prior non-surgical rotations. Assuming the former, a combined Medical and Surgical Objective Structured Clinical Examination (OSCE) at the end of the fourth year could serve to broaden the student's horizons and reduce factual dissociation during the fifth year. PMID- 1755777 TI - Primary adenocarcinoma in a colonic oesophageal segment. AB - A case of primary adenocarcinoma of the colon in a segment used to reconstruct after an oesophageal resection is described. The original lesion was a relatively advanced adenocarcinoma of the gastro-oesophageal junction. An ACPS 'C' colon carcinoma was diagnosed 12 years later. A curative resection was achieved. The literature is reviewed with respect to late complications in colonic interpositions, including primary carcinomas. PMID- 1755778 TI - Benign bladder neck polyp and ureteropelvic obstruction in Beckwith-Wiedemann syndrome. AB - Beckwith-Wiedemann syndrome is recognized for its association with various malignancies but specific urological abnormalities may also be encountered. We report a case of Beckwith-Wiedemann syndrome with two major urological associations--a benign bladder neck polyp and also left hydronephrosis due to ureteropelvic junction obstruction. Whereas the latter is a common urological abnormality, a benign bladder neck polyp is a rare entity and may, thus, be considered to be a component of the syndrome. PMID- 1755779 TI - Duodenal penetration by a Greenfield caval filter. AB - Duodenal penetration by a Greenfield filter occurred in a 77 year old woman 6 years after it had been inserted into her inferior vena cava. The reported incidence of complications associated with the Greenfield filter is low. We report a case of penetration of the device into the duodenum. Plain abdominal X rays demonstrated angulation and deformation of the filter. Cavography and abdominal CT confirmed transcaval penetration of the duodenum. The patient had suffered from severe diarrhoea, night sweats and weight loss which resolved completely with operative removal of the filter. PMID- 1755780 TI - Metastatic carcinoid tumour: stability throughout pregnancy. AB - A patient with asymptomatic histologically proven extensive hepatic metastases of carcinoid tumour had no progression of disease for over 4 years without specific treatment. Throughout a normal pregnancy the hepatic metastases remained stable by clinical, computerized tomography and biochemical criteria. PMID- 1755781 TI - Immunisation against ovine caseous lymphadenitis: comparison of Corynebacterium pseudotuberculosis vaccines with and without bacterial cells. AB - Sheep were immunised with Corynebacterium pseudotuberculosis vaccines prepared from cell-free toxoid or from toxoid with formalin-killed cells of C pseudotuberculosis added. Resistance of sheep to infection was tested 6 months after immunisation by inoculation with caseous lymphadenitis pus. The outcome was assessed 3 months later by slaughter and inspection of the sheep for lesions of caseous lymphadenitis. immunised sheep were adequately protected against infection as shown by a significant reduction in the number of sheep exhibiting lesions compared with control sheep, and by fewer abscesses in affected vaccinated sheep than in affected control sheep. The protective potency of the vaccines was not improved by the inclusion of cells of C pseudotuberculosis. PMID- 1755782 TI - Immunisation against ovine caseous lymphadenitis: efficacy of monocomponent Corynebacterium pseudotuberculosis toxoid vaccine and combined clostridial corynebacterial vaccines. AB - Sheep were immunised with Corynebacterium pseudotuberculosis toxoid formulated as a monocomponent vaccine with aluminium adjuvant or in combination with 5 clostridial antigens, and also in the combined form with sodium selenate. Immunised and control sheep were experimentally infected 16 days after vaccination and slaughtered and inspected after a further 3 months to determine their resistance to infection. All 3 vaccines afforded an equal and high level of protection; 91% of vaccinated sheep exhibiting no lesions of caseous lymphadenitis compared with 51.5% affected sheep in the control group. Average lesion counts were 1.2 per affected vaccinated sheep and 4.5 per affected control sheep. Antitoxin responses to the clostridial toxoids incorporated in the combined vaccines were not affected by inclusion of the C pseudotuberculosis toxoid or the sodium selenate. PMID- 1755783 TI - Immunisation against ovine caseous lymphadenitis: correlation between Corynebacterium pseudotuberculosis toxoid content and protective efficacy in combined clostridial-corynebacterial vaccines. AB - Groups of sheep were dosed with vaccines containing Corynebacterium pseudotuberculosis toxoid combined in varying amounts with 5 clostridial antigens. Resistance of the sheep to infection with C pseudotuberculosis was tested at 1, 6 and 12 months after vaccination by infection with pus from ovine lymph glands actively infected with C pseudotuberculosis. The outcome was assessed 3 months after challenge by slaughter and inspection of the sheep for caseous lymphadenitis lesions. Protection was demonstrated by a significant reduction in the proportion of immunised sheep exhibiting lesions compared with control sheep, and by fewer abscesses in affected immunised sheep than in affected control sheep. A positive correlation was found between amount of C pseudotuberculosis toxoid administered and degree of protection obtained. Chromatographically-purified toxoid induced essentially the same protection, suggesting that anti-toxic immunity is the major factor in protection. PMID- 1755784 TI - Chronic cervical compressive myelopathy in horses: clinical correlations with spinal cord alterations. AB - Histological examination was performed on the cervical spinal cord from 13 horses with chronic cervical compressive myelopathy of 4 to 29 months duration. Structural alterations were correlated with clinical features. At the level of compression, the spinal cord was grossly deformed. Histological alterations included nerve fibre swelling and degeneration, occasional spheroids, astrocytic gliosis, increased macrophage activity and increased perivascular collagen. Myelin degeneration or loss at the level of the compressive lesion was greatest in the ventral and lateral funiculi and less consistently present in the dorsal funiculi. Asymmetry of lesions in the dorsal funiculi was associated with asymmetry of clinical signs in 5 horses. Histological alterations in areas of Wallerian degeneration were similar to that at the level of spinal cord compression, except that perivascular collagen was not increased. Wallerian degeneration was present cranial to the compressed site in the superficial portions of the lateral funiculi and in the middle of the dorsal funiculi. Caudal to the compressed site it was present in the ventral funiculi adjacent to the ventral median fissure and in the middle of the lateral funiculi. Deformation of the spinal cord did not correlate with the severity or duration of clinical signs but was positively correlated with the amount of perivascular collagen increase. The amount of nerve fibre swelling was not correlated with the severity of clinical signs but was negatively correlated with their duration. A rapid loss of nerve fibres apparently occurred early in the course of compression, since there was a marked decrease in the amount of nerve fibre swelling and Marchi stained degenerating myelin with increasing clinical duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755785 TI - Chronic cervical compressive myelopathy in horses: patterns of astrocytosis in the spinal cord. AB - The distribution and morphology of fibrous astrocytes in the cervical spinal cord of normal horses and horses with chronic compressive myelopathy were demonstrated using immunohistochemical staining for glial fibrillary acidic protein. In the spinal cord from normal horses, astrocytes with stellate cell bodies and short processes were irregularly distributed in grey matter. In the white matter, their cell bodies were small and angular in areas adjacent to grey matter and larger and more stellate-shaped in the subpial area. Astrocyte processes were fine, and evenly distributed in a predominantly radial pattern in transverse sections of cord. Gliosis was marked in the spinal cords of horses with cervical compressive myelopathy. In the grey matter at the level of compression astrocytes were often enlarged and rounded, with short, blunt processes, but the gliosis was generally mild. In the white matter, gliosis was obvious in areas of nerve fibre swelling and degeneration at the level of compression and in areas of ascending and descending Wallerian degeneration. The fine radial pattern of astrocyte fibres was replaced by a dense, irregular arrangement. Gliosis persisted in the cords of chronically affected horses after active nerve fibre degeneration had subsided. The areas of gliosis coincided with the areas of Marchi staining for degenerating myelin and with areas of myelin loss in osmium tetroxide post-fixed tissue. Histological observations were consistent with astrocytes replacing areas of extracellular space that remained after nerve fibre degeneration. it is concluded that astrocytic gliosis is a prominent and persistent alteration of the spinal cord of horses with chronic cervical compressive myelopathy. PMID- 1755786 TI - The efficacy of insecticides against the screw-worm fly (Chrysomya bezziana). AB - A number of insecticides used for ectoparasite control in the livestock industry were screened for their efficacy against larvae of the screw-worm fly, Chrysomya bezziana, using in vivo and laboratory tests. Proprietary screw-worm fly treatments (after exposure to outdoor conditions for up to 10 days) were also tested against eggs and adults of C bezziana. Three of these were also evaluated on naturally acquired screw-worm infestations. Residual protection was generally of short duration. Among the organophosphorus compounds, the most effective formulations contained relatively high concentrations (3 to 4% al) of coumaphos, 2.5% fenchlorphos or low concentrations (0.05 to 0.5% al) of diazinon, chlorfenvinphos and fenthion methyl. Two chlorinated hydrocarbon insecticides containing 3% lindane and 5% dieldrin were very effective but are now prohibited for use in Australia. Preparations had serious deficiencies when used under field conditions, especially for treating large, deepseated myiases for which systemic insecticides are recommended. A comparison of methods demonstrated that a laboratory test could supersede live animal experimentation, at least for the initial screening of potential insecticides. PMID- 1755787 TI - Adverse reactions to canine and feline vaccines. PMID- 1755788 TI - Pasteurella multocida-associated septicaemia in a chital deer (Axis axis). PMID- 1755789 TI - Malignant mast cell tumours in horses. PMID- 1755790 TI - Local eradication of Haemonchus contortus using closantel. PMID- 1755791 TI - Oxyhemoglobin saturation following rapid decompression to 18,288 m preceded by diluted oxygen breathing. AB - This investigation studied oxyhemoglobin saturation (SaO2) and cardiovascular indices after rapid decompression (RD). Before RD, fractional inspired O2 concentration (FIO2) simulated the range of product gas from molecular sieve O2 generating systems (MSOGS). Four subjects breathed 1.0-0.80 FIO2 at 6,858 m. After decompression to 18,288 m, the subject received 1.0 FIO2 at a positive pressure of 70 mm Hg for 3 min. There were no incidents of severe hypoxia. The mean SaO2 was 98.0% before RD. After RD, SaO2 was maintained at the pre-RD level for 8 s, decreased rapidly over the next 10 s, and over the rest of the 1st min decreased more gradually to reach approximately 82%. Varying FIO2 before RD had no effect on the alteration in SaO2, heart rate, stroke index, and blood pressure after RD. The MSOGS O2 product range offers adequate protection against hypoxia during RD to 18,288 m. PMID- 1755793 TI - Effect of the prelaunch position on the cardiovascular response to standing. AB - Astronauts spend a minimum of 2 h in the reclined seated position (prelaunch position) prior to the launch of the Space Shuttle. This position favors a cephalad shift of blood volume and subsequent loss of body fluid volume, a physiologic situation associated with cardiovascular deconditioning and orthostatic intolerance following spaceflight. It is not known if the prelaunch position results in cardiovascular deconditioning and, therefore, impaired cardiovascular performance during standing. If so, this might hinder the ability of the crewmember to make an emergency egress from the shuttle during the launch. The purpose of this study was to evaluate the cardiovascular responses of men and women to the stand test before and after 2 h in the prelaunch position. Nine men and nine women performed the stand test before and after 2 h in the seated position (SIT), the prelaunch position (PL), or seated immersed to the neck in water (WI). Heart rate, blood pressure, and cardiac output were measured. Men had higher blood pressures than women and demonstrated increases in blood pressure with standing. There were no other gender differences. SIT did not alter the cardiovascular response to standing, while PL and WI resulted in greater increases in heart rate after 2 h in the position. This increase was only 4 to 7 beats/min greater than after SIT, and was the same for PL and WI. Thus, a small, but significant, degree of cardiovascular deconditioning occurred during the minimum time astronauts spend in the prelaunch position. PMID- 1755792 TI - Hormonal responses of pilots flying high-performance aircraft during seven repetitive flight missions. AB - Hormonal responses during seven repetitive flight missions (7RFM) were evaluated on F-4EJ fighter pilots. The following biochemical constituents were measured: 1) cortisol in saliva; 2) 17-OHCS; 3) unbound cortisol; 4) catecholamines in urine; and 5) electrolytes in urine. Samples were collected at about 30 min before the mission, 20 min after each flight, and in a nonflight day for control. The levels of saliva and urine corticosteroids slightly increased during 7RFM when compared with controls. The concentrations of urine catecholamines during 7RFM were significantly higher than those of preflight and control. These data suggest that flight stresses were moderate for the pilots flying 7RFM. PMID- 1755794 TI - Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs. AB - The separate and combined acute effects of hypoxia (HY-11% O2), head-down tilt (HD-30 degrees) and fluid loading (FL-1.0 L saline) on hemodynamics and pulmonary gas exchange were determined in 17 anesthetized, mechanically ventilated dogs. Both during HY and normoxia (NO), the total respiratory compliance was decreased by HD, attributable to pulmonary vascular congestion. The reductions in compliance were twice as great with FL, indicating pulmonary interstitial edema, which was supported by histological observation of lung tissue. Pressure-flow relationships in the pulmonary circulation indicated that superimposing HD on HY doubled the increase in vascular resistance due to HY alone, while in the systemic circulation the resistance was returned to below NO by HD. A significant positive correlation between the changes in blood volume and pulmonary artery pressure for experimental transitions suggests that a shift in blood volume from systemic to pulmonary circulations and changes in total blood volume probably contributed substantially to these apparent changes in resistance. Pulmonary gas exchange efficiency, whether expressed in terms of shunt or ventilation/perfusion distribution from arterial-end-tidal PCO2 and PO2 differences, showed a significant inverse relationship with pulmonary driving pressure for the experimental conditions imposed. No clear synergistic effects of HY on HD were evident in contributing to pulmonary edema when superimposed prior to FL, but after FL this risk must be considered. PMID- 1755795 TI - Effect of 29 days of simulated microgravity on maximal oxygen consumption and fat free mass of rats. AB - To determine the time course of changes in maximal oxygen consumption (VO2max) and its relationships with body composition, a 29-d simulated microgravity study was initiated with 30 adult female rats (230-280 g) randomly assigned to one of three experimental groups; namely, head-down suspension (HDS) at 45 degrees, horizontal suspension (HS) at 0 degree, or cage control (CC). Five separate exercise performance tests with measurements related to VO2max, treadmill run time, and mechanical efficiency were conducted before suspension and on days 7, 14, 21, and 28. The animals were sacrificed and chemically analyzed for fat and fat-free free mass (FFM) between days 22 and 29. When oxygen consumption results were expressed on an absolute basis (ml.min-1), both suspension groups had significant decreases at day 7. Thereafter, the HDS rats remained significantly decreased, while the HS rats returned to values not significantly different than the presuspension values by day 28. When oxygen consumption was expressed on a relative basis (ml.kg-1.min-1), all groups exhibited significant reductions between 6-8%. Both suspended groups had significantly less fat than the CC rats but had similar values for FFM (p greater than 0.05). When VO2max was evaluated on a FFM basis, the HDS rats had a group mean that was 6% lower than the other two groups, but the difference was not statistically significant. Treadmill run time was significantly reduced in all groups after 28 d with the reduction from pre-suspension values being more pronounced with HDS animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755796 TI - Effects of long duration spaceflight on human T lymphocyte and monocyte activity. AB - Experiments were performed on blood samples from 5 cosmonauts in order to investigate the effects of long duration spaceflight (26 to 166 days) on immune activity. The experiments were performed on cultured mononuclear cells purified from blood samples collected during the preflight period and 24 h after landing. The production of interleukin 2, which is the major cytokine involved in T lymphocyte proliferation, was found to be enhanced after flight in some individuals, whereas the ability of mitogen-stimulated cells to express interleukin 2 receptor was impaired 24 h after flight for two cosmonauts out of five. Normal interleukin 2 receptor expression was obtained in all cases when lymphocytes were directly activated by a protein kinase C activating phorbol ester. On the other hand, no significant changes were observed in interleukin 1 production by cultured peripheral blood mononuclear cells. Lastly, the distribution of T lymphocytes subsets was examined in peripheral blood sampled 24 h after landing and was found to be within normal values. PMID- 1755797 TI - Vector-averaged gravity alters myocyte and neuron properties in cell culture. AB - To investigate whether changes in the gravitational field of developing neurons and myocytes affect cellular development, we rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat. Rotation in the clinostat produces, from the cells' perspective, a "vector-free" gravity environment by continuous averaging of the vector. In this way, rotation in the clinostat simulates the microgravity of space where the gravity vector is substantially reduced. At rotation rates of 1-50 rpm, cellular and nuclear areas of myocytes were significantly enlarged and the number of presumptive nucleoli increased. In neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after cessation of rotation. Since our data are generally consistent with findings from other cell types subjected to spaceflight, we suggest that the vector-free gravity environment of the clinostat appears to simulate, at least in part, the microgravity of space. Our data further show that cellular processes are sensitive to altered gravity and suggest that cell development in the microgravity of space may be significantly altered. PMID- 1755798 TI - Brief reactive psychosis in naval aviation. AB - Five naval aviation personnel diagnosed with brief reactive psychosis (BRP) have appeared before the Special Board of Flight Surgeons (SBFS) at the Naval Aerospace Medical Institute (NAMI). These cases demonstrate the challenges in diagnosis and disposition that face the clinical aeromedical specialist in evaluating the aviator who develops psychiatric symptoms. We discuss the aeromedical factors that must be considered when contemplating returning aviators with psychiatric diagnoses to flying duties. Sudden behavioral changes in aviation personnel require a systematic assessment, thorough documentation, and continuing reevaluation. The differentiation between organic and functional etiologies may be difficult. Final disposition may require consultation with experienced physicians skilled in both aviation psychiatry and neurology. PMID- 1755799 TI - Spinal X-ray screening of high performance fighter pilots. AB - Neck pain and neck injury are common complaints among military aviators flying high performance (HPF) aircraft. Since all candidates for military flying training with the Royal Norwegian Air Force have to meet HPF medical standards, medical selection procedures include a radiological examination of the spine. Nine films of the vertebral column are made with emphasis put on cervical structures. Among 232 applicants, 527 deviations from normal conditions were described--anomalies, degenerative changes and deviations of posture--which average 2.27 diagnoses per spine X-rayed. Of the candidates, 80 were considered entirely within normal limits; 20 were rejected due to the roentgen findings; and five candidates were excluded on final evaluation, their radiological diagnoses contributing to the decision. Although most changes are slight, many significant conditions are demonstrated among young healthy individuals. Since the population is highly selected, the figures we present may be minimum numbers in a western industralized society. PMID- 1755800 TI - Estimate of requirements for detection and treatment of hypercholesterolemia in U.S. Army aviators. AB - In May 1988, the Army Surgeon General issued guidelines and a preliminary plan for evaluation and treatment of hypercholesterolemia, based on the recommendations of the National Cholesterol Education Program Expert Panel. Implementation of this plan in the aviation population would require an unknown number of aviators to undergo testing and possibly therapy for hypercholesterolemia. This study uses a mathematical model and information from the Aviation Epidemiology Data Register to estimate the number of aviators who would require detailed lipoprotein analysis and at least dietary therapy, based on evaluation of their total serum cholesterol and other coronary artery disease (CAD) risk factors, as described in the expert panel report. The model predicts that at least 27% of all aviators would require LDL screening, and 24.6% of all aviators would require dietary or drug therapy. PMID- 1755801 TI - Decompression sickness: U.S. Navy altitude chamber experience 1 October 1981 to 30 September 1988. AB - This study reports the incidence of decompression sickness (DCS) occurring in U.S. Navy altitude chambers in association with physiological training of aircrews for the 7-year period from 1 October 1981 to 30 September 1988. There were 140 total cases of DCS in 136,696 chamber exposure, an incidence of 0.10%. Among trainees, there were 78 cases in 111,674 exposures, and incidence of 0.07%. Among inside observers, there were 62 cases in 25,022 exposures and incidence of 0.25%. The incidence of DCS among inside observers was reduced almost two-fold over the last Navy report and is the lowest reported since 1973. Reasons for the reduction are discussed. In addition, analysis of the data includes types of DCS, symptoms, frequency of joint involvement, predisposing factors, altitude and time of onset of DCS, and treatment tables employed. PMID- 1755802 TI - Flight psychology at Sheppard Air Force Base. AB - Flight psychology is the application of psychological principles to the unique environment of the aviator in order to enhance training, flight safety, and mission accomplishment. At Sheppard Air Force Base, TX, flight psychology is a cooperative effort between a clinical psychologist and the aeromedical services, with the former acting as a consultant to the latter. The primary focus of the flight psychology program is stress management, including managing the stress response of airsickness, for students in the Euro-NATO Joint Jet Pilot Training (ENJJPT) program. Psychological assessments of flying personnel, air traffic controllers, and individuals being considered for special duties constitute a valuable contribution to aeromedical services. We present clinical vignettes to illustrate the interaction of the flight psychologist and aeromedical services, and the effect on flying training and flight safety. PMID- 1755803 TI - A comparison of flight and non-flight sick call visits to a U.S. Army aviation medicine clinic. AB - In a U.S. Army aviation medicine program, flight surgeons provide primary clinical care for the units they support. Routine outpatient care (sick call) is performed daily on a walk-in basis. This study describes the diagnoses associated with flight and non-flight personnel reporting to sick call in an Army aviation medicine clinic. Data were collected over a 1-year period at an Aviation Troop Medical Clinic (TMC) supporting an aviation brigade consisting of 530 aircrew and 1,220 support personnel. A total of 5,793 sick call visits were made, 73% of which were initial visits, the remainder being second or subsequent visits. Aircrew evaluations accounted for 29% of the total. Major reasons for visits were illness (56%), injury (34%), and supplemental care (10%). However, substantial differences were noted between flight and non-flight patients. Overall, non aircrew visits accounted for the bulk of the flight surgeons' clinical workload during sick call. PMID- 1755804 TI - Airshow disaster plans. AB - Airshows require careful medical planning. Disaster drills and coordination between all rescue agencies are necessary. Rescue personnel and command post must be highly visible. Good communication includes dedicated radio frequencies at the site, dedicated phone lines to hospitals, and multiple back-ups. Security personnel should use yellow police tape for crowd control, and volunteers must be supervised. Key medical elements include efficient triage and stabilization at the site, adequate medical personnel, equipment dispersed within the crowd, rapid transportation including helicopters, and crisis intervention. Separate areas are needed for persons with minor injuries, relatives and friends, the press, and a morgue. Disaster plans for airshows have unique aspects. A predetermined time benefits planning. Airports often have pre-existing medical facilities, and participating military agencies may have additional resources. Burns and inhalation injuries predominate at airshow accidents. Enlarging spectator safety zones and modifying aerobatic maneuvers can prevent injury. PMID- 1755805 TI - An operationally oriented approach to medical care in space. AB - As plans to bring the United States into the realm of continuously manned space operations are written, questions concerning the medical support of those operations have been raised. A review of the simple, time-tested principles that guide military operational medicine can be applied to medical care in space. Based on this operational approach, I conclude that a successful medical team must understand the mission, identify medical resources, define medical evacuation capabilities, anticipate medical issues and plan solutions, and develop facility requirements. Once all this has been accomplished, appropriate selection and training of medical personnel completes the preparation. PMID- 1755807 TI - Growth factors in endocrinology. PMID- 1755806 TI - Cases from the aerospace medicine residents' teaching file. Case #47. Primary pulmonary coccidioidomycosis. AB - This case report on primary pulmonary coccidioidomycosis outlines a typical presentation in an individual at high risk and the pitfalls that can occur to practitioners unfamiliar with this disease. The patient was a 36-year-old black male who presented with an initial abnormal chest X-ray and who eventually was correctly diagnosed and improved on a 30-day course of ketoconazole. This patient showed no signs of dissemination. PMID- 1755808 TI - Epidermal growth factor and transforming growth factor alpha. AB - I have attempted here to outline the basic biochemical knowledge that we have now secured on the EGF family of proteins. In the future we will learn much more about the differential role of EGF versus TGF-alpha, about the physiological significance of amphiregulin, the newest member of this family, and about the roles of TGF-alpha and amphiregulin in cancer. Many questions remain. What is the importance of these factors in embryogenesis and fetal development? Is there an involvement of the EGF-like domains of extracellular proteins in cell-to extracellular-matrix interactions? Do these extracellular matrix EGF-like entities function in a similar manner to fibroblast growth factor in cell growth and in mediating the relationship of cells to the extracellular matrix? What is the significance of cell membrane-bound forms of EGF and TGF-alpha as potential cell-to-cell contact regulators? What is the role of the viral EGF-like proteins in the viral infective and transforming process? These and other questions will be addressed in the next decade. The key question has already been well stated: 'what is the normal physiological role of EGF during development and homeostasis? The answers to these and a host of other questions must be found before we can fully comprehend this important regulatory system' (Cohen, 1987). PMID- 1755809 TI - Transforming growth factor beta/inhibin family. PMID- 1755810 TI - Anti-mullerian hormone. PMID- 1755812 TI - Growth factor control of pancreatic B cell hyperplasia. AB - Pancreatic B cell hyperplasia is an essential feature of normal fetal and childhood development in order to maintain insulin availability to the growing organism. While glucose, amino acids and pituitary growth hormone have all been shown to increase B cell DNA synthesis in cultures of isolated islets of Langerhans, there is also evidence for a local regulation of growth by trophic factors. IGF-I and IGF-II are expressed and released by pancreatic B cells and have the capacity to act as B cell mitogens. Specific IGFBPs are also released by islets which may modulate the bioactivity of IGFs. While IGF release is not under acute nutrient control, at least in vitro, the mitogenic actions of growth hormone on islets are mediated in part by an increase in the local release of IGF I. Other peptide growth factors reported to influence B cell DNA synthesis include PDGF, EGF, TGF-beta and TRH. The contribution of peptide growth factors to pathological abnormalities of pancreatic islet growth is unknown. PMID- 1755811 TI - Growth and differentiation. PMID- 1755813 TI - Growth factors and the anterior pituitary. AB - Normal growth and secretion in the pituitary gland are dependent upon the co ordinated action of a large number of extracellular growth factors, neuropeptides and peripheral hormones acting on their respective cellular receptors and via complex intracellular signalling pathways. The pituitary and hypothalamus are exposed to a large number of growth factors, several of which have well documented effects on secretory function and may act as physiological modulators of pituitary hormone synthesis and release. IGF-I, for example, almost certainly acts as a feedback regulator of GH secretion. Despite well-documented mitogenic effects in other tissues, little is known about the role of these growth factors in normal pituitary cell turnover, compensatory hyperplasia or adenoma formation. There is now good evidence, however, that at least some of the hypothalamic releasing peptides are mitogenic for their respective pituitary cell subpopulations. The aetiology of pituitary tumours remains poorly understood but some appear to develop as a result of somatic mutation. Such mutations could enhance growth by causing altered expression of growth factors or their receptors, or constitutive activation of proteins involved in the intracellular mitogenic signal. Abnormalities have been documented at each of these levels in human pituitary tumours. The identification of an activating point mutation in the alpha subunit of Gs, the stimulatory regulatory peptide of adenylyl cyclase, in a proportion of somatotroph adenomas represents a major advance in our understanding of pituitary tumour pathogenesis. This and other findings may ultimately lead to new therapeutic approaches to the management of pituitary disease. PMID- 1755814 TI - The ovary. AB - The functions of the ovary can be described as a storehouse for oocytes as well as a factory to produce mature oocytes at the appropriate time for fertilization and hormones at the appropriate time and in the appropriate quantities to assure fertility. A complex multiple-job specification such as this requires control processes which allow all facets to operate successfully at the same time, and in a co-ordinated manner. This can only be achieved by hypothesizing control at several levels, namely, externally via gonadotrophins (and perhaps GH and prolactin), and internally via local regulators, where the local regulators control the gonadotrophin-independent processes and fine tune the gonadotrophin dependent processes. The available evidence is consistent with a role for local regulators in the control of follicular and luteal function in the ovary. In most cases, however, the nature of the local regulator involved in a particular process is not known. On the other hand, the list of candidates continues to increase (see Table 1). A priority for future research will be to firmly establish many of these substances as local regulators and to understand how and when they exert their actions, particularly in vivo. A particularly complex question concerns the potential interaction between the local regulators which have either similar or opposing actions. The clinical significance of local regulation in the ovary is yet to be fully appreciated. The addition of GH to gonadotrophin therapy for ovulation induction (Homburg et al, 1988) is the first example of the application of findings from basic research on local regulators in the ovary. It may be that clinical syndromes such as resistant ovary syndrome, polycystic ovarian disease and luteinized unruptured follicle have some perturbation of local regulator production or action, which, if defined, would underline the importance of local regulation and could offer a means of treatment. PMID- 1755815 TI - Growth factors as mediators of testicular cell-cell interactions. AB - The development of testicular function may require local cell-cell interactions to regulate tissue growth and differentiation. Locally produced growth factors may mediate the differential growth of mesenchymal, epithelial and germinal cells that occurs during fetal, prepubertal and postpubertal testis development. The complex co-ordination of differential and temporal cellular growth suggests that a variety of locally produced factors may be involved. Presently, a number of growth factors have been identified in the testis, including IGF-I, TGF-alpha, TGF-beta, NGF, IL-1, FGF, SGF and SCSGF. These factors may mediate interactions involving growth stimulation, growth inhibition and differentiation in this tissue (Table 2 and Figure 1). Endocrine agents are also necessary for testis development and function. In many organs, endocrine hormones appear to alter local cell-cell interactions. Similarly, gonadotrophins may modulate growth factor interactions within the testis. Understanding testicular cell-cell interactions involving growth factors requires evaluation of the cellular site of factor expression, production, secretion, target cell action and in vivo significance. Presently, none of the proposed cell-cell interactions involving growth factors have evaluated all these criteria. Further cellular and molecular analysis of these intercellular interactions are necessary to clarify the role of growth factors in the development and maintenance of testicular function. PMID- 1755816 TI - Growth factors in the uterus: steroidal regulation and biological actions. AB - Rapid progress has been made within the last 5-6 years in characterizing polypeptide growth factors in uterine tissues and fluids. There is convincing evidence that their synthesis and/or secretion is regulated by steroid hormones. The possibility that these growth factors play a central role in growth and development of the uterus or placenta is suggested by the presence of their receptors on uterine or placental cells and their stimulatory effects on these cells in vitro. Since growth factors interact synergistically and also have non mitogenic functions, the presence of a variety of these factors in the uterus suggests that they probably regulate various aspects of uterine function through complex autocrine and paracine pathways. However, experimental models need to be designed that will permit a more detailed analysis of the actual role of these factors in utero. Fruitful approaches may be to administer neutralizing antibodies or blocking peptides so as to antagonize uterine growth factor action, or to develop appropriate transgenic animals. These and other lines of study should help us to understand the role of growth factors in development of the immature uterus, growth of the placenta or gravid uterus, repair and angiogenesis of the endometrium, and uterine pathology. PMID- 1755817 TI - The mammary gland. AB - In vivo studies have shown that the growth of the mammary gland is regulated by a complex synergistic interaction of protein, steroid and thyroid hormones, but it has proved difficult to fully reproduce these effects in vitro. It is becoming apparent that the hormones classically recognized as involved in mammary growth (oestrogen, progesterone, prolactin, GH, adrenal corticoids, triiodothyronine) bring about effects on epithelial cell proliferation at least in part through growth factors produced at distant sites (such as the liver) and also locally by mammary tissue, both parenchyma and stroma. Growth factor receptors can be demonstrated in mammary tissue. Receptor occupancy generates intracellular signals which enable cells to progress through the cell cycle, leading in ways still not understood to DNA synthesis and cell division. Within the mammary gland there probably exists a balance of stimulatory factors (such as IGFs and EGF/TGF alpha) and inhibitory factors (such as TGF-beta). Interactions between epithelial and stromal cells, involving growth factors and the extracellular matrix, bring about pattern formation. Growth factors may also play some part in mammary differentiation and function, although the evidence here is less clear. Growth factors are also implemented in the failure of growth regulation which neoplastic transformation represents. Breast cancer cells can synthesize and secrete a variety of growth factors which may stimulate tumour growth through local autocrine/paracrine mechanisms. The oestrogen dependence of some breast cancers may involve oestrogen regulation of and interaction with growth factors, progression to hormone independence involving loss of this control. It is significant that the proteins which protooncogenes encode include growth factors and growth factor receptors. Much remains to be learnt about the nature and control of growth factors produced by and acting on the mammary gland. In breast cancer, this research offers the possibility of new methods of diagnosis and treatment. PMID- 1755818 TI - The use of transgenic animals to study the role of growth factors in endocrinology. AB - Transgenesis is identified as being of special interest in the study of growth factors where their multicellular origins and complex interactions make them particularly difficult to characterize using classical experimental approaches developed to investigate hormones originating in specialized cells in discrete glands. Through allowing molecular 'tinkering' in intact animals, transgenesis enables specific growth factors to be 'ablated or replaced' from specific tissues and organs and target cell response and impact of modulatory factors such as binding proteins to be explored in the intact animal. To the endocrinologist, the potential applications of such technology are legend. This chapter provides a brief overview of the technique and provides linkages to the rapidly developing body of literature in establishing transgenesis in growth factor research. PMID- 1755819 TI - [Postanesthetic complications in the horse. Evaluation of anesthesia in the last 28 years (1962-1989)]. AB - The anesthesia routine in the horse is briefly explained. 35 postanesthetic complications resulted from the total of 4364 cases of anesthesia. They are evaluated by means of the duration of anesthesia, the time of paresis, the exemplary courses of enzymes as well as the distribution of race and sex and their ratio towards all cases of anesthesia. Finally a list of demands concerning the operative and postoperative phases is compiled to minimize postoperative myositis (PAM) and lameness (PAL). PMID- 1755820 TI - [Radiographic studies of ossification of the hoof cartilage of horses and its clinical evaluation]. AB - Radiographic examination is a valuable means for the identification of ossified lateral cartilage. The extent and stages of development of the ossification can be determined. The active stage of development of ossified lateral cartilage, which by itself can provoke lameness, can be defined. By means of the X-ray it is tried to differentiate the three kinds of ossification: the enchondral, the peri- and parachondral ossification of the lateral cartilage. Centres of ossification and fractures of the ossified lateral cartilage are described. PMID- 1755821 TI - [The effect of the sedative and analgesic detomidine for laryngoscopy of adult horses and foals]. AB - Detomidine was used in this field trial effectively as a sedative and analgesic for laryngoscopic examinations in a total of 193 foals and 806 mature horses (Hanoverians). Detomidine was given either i.v. in foals 3 to 11 months old (20 micrograms/kg) and in mature horses (15 micrograms/kg), or i.m. in foals below 6 months of age (35 micrograms/kg). After i.v. administration, laryngoscopy was tolerated in more than 90% of all animals without additional use of a twitch, while in foals treated i.m. more than 70% required a twitch in order to enable this procedure. The effectiveness of detomidine was influenced by dose, route of administration, the time interval between treatment and examination and the degree of excitement before treatment, but not by sex. Profound bradycardia was evident in all treated animals, but arrhythmias were seen only in animals older than 4 months and were more pronounced in horses with a lower resting heart rate. These cardiovascular responses never endangered any of the treated animals. A transient dyspnea was seen in 13 foals (6.7%) and 10 horses (1.2%). Other side effects were rare. The foaling rate of 297 mares treated at any time during the first 8 months of pregnancy was 66.7%. A comparison with 5499 untreated, contemporary controls revealed a foaling rate of 61.0%. Hence treatments had no adverse effects on pregnancies. PMID- 1755822 TI - [Estimation of the occupational radiation exposure during radiographic studies of horses]. AB - Radiography of horses in veterinary practice is done normally with quite simple equipment. Thereby radiation protection is easily neglected. In this investigation sources of mistakes are demonstrated. The possible exposure of staff is evaluated by dose measuring over a long period of time. It can be stated that following the most simple radiation protection there will never be a significant exposure of staff. PMID- 1755823 TI - [Heart arrhythmias in horses caused by delays of conduction in the atrioventricular nodes and in the bundle of His]. AB - The clinical importance of the AV blocks in horses discussed. The second degree AV block is a symptom of the adaptation of the heart to increased workload and it is not an indication of a good performance. PMID- 1755824 TI - [Phenol in the serum of dogs and horses and its clinical significance]. AB - Reference values of serum phenols between 0.3 and 0.7 mmol/L in dogs respectively between 0.25 and 0.37 mmol/L in horses are determined. In dogs increased phenol values were found frequently in hepatopathy. Furthermore elevations, particularly in diseases of the gastrointestinal tract, were obtained; especially in hemorrhagic enteritis of dogs, associated with parvovirosis, and in mechanical ileus of the small intestine and the large intestine respectively in horses. In renal and endocrine diseases increased phenol values were seldom obtained. PMID- 1755825 TI - [Monitoring of the oxygen saturation of horses during halothane anesthesia using pulse oximetry in the nasal septum]. AB - The use of pulse oximetry for on-line monitoring of oxygen saturation of arterial blood using a probe on the nasal septum is described in the horse. When compared to the results of blood gas analysis an excellent correlation between the two methods for measuring oxygen saturation is found. Nevertheless a discrepancy between the values for oxygen saturation provided by either method is found. This can lead to misinterpretation of oxygen saturation values generated by the pulse oximeter. The cause of this discrepancy is not clear but differences in measuring principle, presence of dyshemoglobins and differences in absorption characteristics of hemoglobin are to be ruled out as major contributors. Contrary to findings in several other animal species occasionally double counting of pulse frequency by the pulse oximeter is seen. PMID- 1755826 TI - The helix-loop-helix domain: a common motif for bristles, muscles and sex. AB - Three apparently unrelated developmental processes--mammalian myogenesis, the choice of neural fate and sex determination in Drosophila--are controlled by a common mechanism. Most of the genes governing these processes encode transcriptional factors that contain the helix-loop-helix (HLH) motif. This domain mediates the formation of homo- or heterodimers that specifically bind to DNA through a conserved basic region adjacent to the HLH motif. Dimers differ in their affinity for DNA and in their ability to activate transcription from HLH binding-site containing promoters. In addition, the activity of HLH proteins is inhibited by dimerization with another class of HLH proteins that lack a basic domain entirely or have an altered one. These structural properties provide a molecular mechanism to explain the synergistic and antagonistic functional relations among the HLH encoding genes that control several developmental pathways. PMID- 1755827 TI - New enzymes for old: redesigning the coenzyme and substrate specificities of glutathione reductase. AB - A set of amino acid side chains that confer specificity for the coenzyme NADPH and the substrate glutathione in the flavoprotein disulphide oxidoreductase, glutathione reductase, has been identified. Systematic replacement of these amino acid residues in the coenzyme-binding site switches the specificity of the enzyme from its natural strong preference for NADPH to a marked preference for NADH. The amino acids replaced all lie in a structural motif within the dinucleotide binding domain of the protein. Since this domain is a feature common to most dehydrogenases (reductases) that use nicotinamide coenzymes, it may be that the coenzyme specificities of all such enzymes can be manipulated in this way. Similarly, amino acid residues involved in the selective recognition of trypanothione by trypanothione reductase, an enzyme related to glutathione reductase and exclusive to trypanosomatids, were identified. Suitable mutation of the corresponding residues in E. coli glutathione reductase switched its substrate specificity towards trypanothione. A better understanding of the substrate specificity of these enzymes could open up a route to the chemotherapy of trypanosomal infections. PMID- 1755828 TI - Alternative splicing of fibronectin: three variants, three functions. AB - Fibronectin (FN) is a multi-functional extracellular matrix protein required for cell adhesion and migration, blood clotting, wound healing, and oncogenic transformation. The functional complexity is paralleled by structural diversity in that multiple forms of FN are generated by cell type-specific alternative splicing. In the rat, up to 12 different combinations of the three alternatively spliced segments (EIIIA, EIIIB, and the V region) are produced. What effects do these segments have on FN function? Recently, progress has been made in the identification of specific activities for the three variants of the V region, V120, V95, and V0. FN-mediated cell adhesion, FN synthesis and secretion, and incorporation into blood clots are differentially affected by these isoforms. These results suggest that cellular behavior is modulated by environmental cues provided by different types and proportions of alternatively spliced FN variants. PMID- 1755829 TI - How do cells respond to ultrafine surface contours? PMID- 1755830 TI - Transfer of yeast artificial chromosomes from yeast to mammalian cells. AB - Human DNA can be cloned as yeast artificial chromosomes (YACs), each of which contains several hundred kilobases of human DNA. This DNA can be manipulated in the yeast host using homologous recombination and yeast selectable markers. In relatively few steps it is possible to make virtually any change in the cloned human DNA from single base pair changes to deletions and insertions. In order to study the function of the cloned DNA and the effects of the changes made in the yeast, the human DNA must be transferred back into mammalian cells. Recent experiments indicate that large genes can be transferred from the yeast host to mammalian cells in tissue culture and that the genes are transferred intact and are expressed. Using the same methods it may soon be possible to transfer YAC DNA into the mouse germ line so that the expression and function of genes cloned in YACs can be studied in developing and adult mammalian animals. PMID- 1755831 TI - The biology of cancer metastasis or, 'you cannot fix it if you do not know how it works'. AB - The major cause of death from cancer is the relentless growth of metastases that are resistant to conventional therapy. The pathogenesis of a metastasis is complex and requires that tumor cells complete a sequence of potentially lethal interactions with various host factors. The finding in 1973 that metastasis is a selective process and the finding in 1977 that malignant neoplasms are heterogeneous and contain few preexisting metastatic subpopulations have added a new dimension to our understanding of cancer and its spread. This understanding is now contributing to the design of better therapies against disseminated metastasis. PMID- 1755832 TI - Nucleotide sequence of the Clostridium thermocellum laminarinase gene. AB - The sequence presented (1022 bp) shows the Clostridium thermocellum laminarinase gene (lam1) and its flanking regions. The gene lam1 comprises an open reading frame of 726 nt, encoding a 242-aa protein with predicted Mr 27661. The ORF startswith the translation initiation codon ATG. This ATG codon is preceded at a spacing of 7 bp by a potential ribosome binding site (GGAGGT). A putative signal peptide was identified (the potential cleavage site is between position 27-28 aa). The comparison of the primary protein sequence with other beta-1, 3-1, 4 glucanases showed extensive homology for Bacillus amyloliqefaciens and Bacillus subtilis glucanases (identity-46.7%; similarity-57.0%). PMID- 1755833 TI - Endothelin-1 is expressed and released by a human endothelial hybrid cell line (EA.hy 926). AB - A permanent vascular endothelial cell line, EA.hy 926, was shown to express endothelin-1 (ET-1) mRNA and to secrete big ET-1 and ET-1 into culture medium. The concentration of both big ET-1 and ET-1 was significantly increased in EA.hy 926 culture medium by phosphoramidon, a metalloproteinase inhibitor, suggesting that phosphoramidon sensitive protease(s) may be responsible for the degradation of ET-1 and big ET-1. EA.hy 926 cells responded to various regulators of ET-1 similarly as primary human vascular endothelial cells. The production of ET-1 was increased by thrombin and decreased by vasodilators such as atrial natriuretic peptide, brain natriuretic peptide and nitroprusside, and by 8-bromo cyclic GMP and papaverine. This continuous human endothelial hybrid cell line could facilitate studies of regulation of ET-1 production in human endothelial cells, which in primary cultures have limited replication potential. PMID- 1755834 TI - Normal cholesterol synthesis in human cells requires functional peroxisomes. AB - To evaluate the importance of peroxisomes in cholesterol metabolism we measured the rate of cholesterol synthesis in cultured skin fibroblasts from 16 patients in whom deficiency of peroxisomes had been established. Seven complementation groups were studied, consisting of one six member group, one three member group, three groups comprising single cases and two groups with two cases each. On the average, cholesterol synthesis was below control values in all the 16 peroxisome deficient fibroblast cell cultures. The range of cholesterol synthesis in these cells was 2% to 84% of normal values. These data strongly suggest that peroxisomes are essential for normal cholesterol synthesis in human fibroblasts. PMID- 1755835 TI - Stabilization of actin by phalloidin: a differential scanning calorimetric study. AB - We have used differential scanning calorimetry to study the effects of phalloidin on F and G actin stability. For F actin, saturating concentrations of phalloidin induced an important shift on the transition temperature, Tm, from 69.5 degrees C to 83.5 degrees C. However, the calorimetric enthalpy remained unchanged. Using lower phalloidin concentrations, monomers linked to phalloidin, as well as neighboring unlinked monomers, were both stabilized. Contrary to previous reports, phalloidin was also shown to affect G actin, shifting its Tm from 59.5 degrees C to 75 degrees C. Two mechanisms are proposed to explain this finding: first, it could indicate a real interaction of phalloidin with G actin, and second, heating of the specimen during the scan could have induced polymerization of some G actin to the F form. The resulting F polymer would then interact with phalloidin, thus shifting the equilibrium between G and F actin towards the polymeric form. PMID- 1755836 TI - The role of phosphorylation in development of tight junctions in cultured renal epithelial (MDCK) cells. AB - We have explored the effect of the protein kinase inhibitor H7 on tight junction formation in a MDCK cell model for the development of cell-cell contact, tight junctions and epithelial polarity: the "Ca++ switch" model. In this developmental model, which is thought to mimic processes during the early morphogenesis of epithelial tissues, the protein kinase inhibitor H7 markedly inhibits the development of transepithelial resistance of confluent MDCK cells during the "switch" from low (1-5 microM) to normal (1.8 mM) Ca++ media compared with control MDCK cells. Moreover, indirect immunofluorescence using specific antisera against two tight junctional proteins, ZO1 and cingulin, revealed that H7 inhibits the sorting of these proteins from an intracellular site to the lateral surfaces of MDCK cells when the Ca++ in the medium is raised. These data suggest protein kinase mediation in sorting events that lead to the assembly of tight junctions. PMID- 1755837 TI - Lactosylceramide stimulates aortic smooth muscle cell proliferation. AB - We have investigated the effects of various sphingolipids on aortic smooth muscle cell proliferation employing viable cell counting, [3H] thymidine incorporation into DNA and the release of lactate dehydrogenase. Assays for UDP Gal: GlcCer Bl 4 galactosyltransferase (GalT-2) in control and treated cells were pursued simultaneously. Lactosylceramide stimulated cell proliferation in the order of 5 fold. Antibody against LacCer but not GbOse3Cer blocked the proliferative effects of LacCer in these cells. This phenomena was specific for aortic smooth muscle cells as LacCer decreased cell viability of aortic endothelial cells and had no effect on pulmonary endothelial cells. D-PDMP inhibited the activity of GalT-2 in smooth muscle cells and markedly prevented cell proliferation. In contrast, L PDMP stimulated the activity of GalT-2 in smooth muscle cells and stimulated cell proliferation. Antibody against GalT-2 inhibited cell proliferation. Our findings suggest that the activation of GalT-2 leads to increased LacCer levels, which in turn, may be involved in aortic smooth muscle cell proliferation. PMID- 1755838 TI - Inhibitory effect of thyrotropin releasing hormone on spontaneous proliferation of mouse spleen lymphocytes in vitro. AB - The effects of thyrotropin releasing hormone (TRH) and of TRH-like tripeptide pGlu-His-Gly-OH (colon mitosis inhibitor, CMI) on spontaneous proliferation of murine splenocytes were investigated in vitro. The 3H-thymidine incorporation into splenocyte DNA was used as an index of proliferation. It was found that TRH suppressed the proliferation of splenocytes. In contrast, CMI was ineffective by itself but used together with TRH blocked the effect of the latter. PMID- 1755839 TI - Identification of potentially neurotoxic pyridinium metabolite in the urine of schizophrenic patients treated with haloperidol. AB - Evidence that the parkinsonian inducing agent MPTP is biotransformed to a pyridinium species that selectively destroys nigrostriatal neurons in humans and subhuman primates has prompted studies to evaluate the metabolic fate of the structurally related neuroleptic agent haloperidol. With the aid of a highly sophisticated atmospheric pressure ionspray HPLC/MS/MS assay, unambiguous evidence has been obtained for the presence of the haloperidol pyridinium species in extracts of urine obtained from haloperidol-treated patients and in extracts of NADPH-supplemented human liver microsomal incubation mixtures containing haloperidol. The potential significance of the formation of this putative neurotoxic pyridinium species is considered. PMID- 1755840 TI - Structural properties of human carbonic anhydrase II at pH 9.5. AB - The structure of human carbonic anhydrase II at pH 9.5 has been studied by X-ray crystallographic methods to 2.2 A resolution. These studies complement those performed under acidic conditions in which the catalytically-important proton shuttle group, His-64, exhibits conformational mobility about side-chain torsion angle chi 1. However, no structural changes are observed in the conformation of His-64 at high pH. Therefore, we conclude that the protonation of His-64 (as well as zinc-bound hydroxide) may be a factor which contributes to the predominantly "out" conformation for His-64 observed at low pH. PMID- 1755841 TI - A common precursor for a putative hemorrhagic protein and rhodostomin, a platelet aggregation inhibitor of the venom of Calloselasma rhodostoma: molecular cloning and sequence analysis. AB - Rhodostomin is a platelet aggregation inhibitor secreted by the venom gland of Calloselasma rhodostoma. We report here the isolation of a 1.67-kilobase (kb) lambda gt11 cDNA clone using degenerate oligonucleotide probe based on a partial amino acid sequence of rhodostomin. The amino acid sequence deduced from an open reading frame of the cDNA indicates that (i) the 68-amino acid sequence of rhodostomin is located at the carboxyl terminus of the precursor polypeptide and (ii) a peroxisomal targeting sequence (ser.his.ala.) exists between the stop codon and the rhodostomin sequence of the precursor. Since the amino-terminal segment of the deduced sequence shows a high degree of identity with hemorrhagic proteins, which are zinc-metalloproteinases, found in the venom of some crotalid and viperid snakes, our results also predict the existence of at least one such hemorrhagic protein in the venom of Calloselasma rhodostoma. The derivation of a platelet aggregation inhibitor and a hemorrhagic protein from the same precursor protein is consistent with the fact that these proteins may be synergistic in function. PMID- 1755842 TI - Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene. AB - The molecular basis of the ferrochelatase defect responsible for human Erythropoietic Protoporphyria (EPP), a usually autosomal dominant disease, was investigated in a family with an apparently homozygous patient. Two mutations of the ferrochelatase gene were identified by sequencing the proband's cDNA after in vitro amplification of the mRNA and subcloning of the amplified products. One mutation results from a G to T transition at nucleotide 163 which produces a glycine to cysteine substitution at amino-acid residue 55 (G-55-C). The other one was a G to A change at nucleotide 801, leading to a methionine to isoleucine substitution at amino-acid residue 267 (M-267-I). This EPP patient was then double heterozygous and as expected each of his parents carried one of the mutations. A second similar EPP patient was screened for these mutations with negative results, showing a genetic heterogeneity in EPP. PMID- 1755843 TI - Scanning tunneling microscopy of human erythrocyte membranes. AB - Images of surfaces of human erythrocyte ghosts, lecithin liposomes, spectrin, erythrocyte membrane skeleton, concanavalin A and concanavalin A--decorated erythrocyte ghosts were obtained by scanning tunneling microscopy. The dimensions and surface topography of some membrane structures are described and discussed. PMID- 1755844 TI - A DBL-homologous region of the yeast CLS4/CDC24 gene product is important for Ca(2+)-modulated bud assembly. AB - The CLS4/CDC24 is essential for the budding process of the yeast Saccharomyces cerevisiae. Disruption of the CLS4/CDC24 gene is lethal, and expression of the CLS4 product under the control of the GAL1 promoter is sufficient for cellular growth. The CLS4 product is detected in yeast cell lysate with an apparent molecular mass of 93 kD (854 amino acid residues) and shows homology with the human DBL oncogene product. Temperature-sensitive cdc24-1 mutation is located in the N-terminal portion of the protein whereas Ca(2+)-sensitive cls4-1 mutation is present after the DBL-homologous region (amino acid residues 281-518) near the putative Ca(2+)-binding site. Mutations within the DBL-homologous region are responsible for the Ca(2+)-sensitive phenotype. Thus the CLS4 gene product seems to have several functional domains within the molecule essential for bud assembly. PMID- 1755845 TI - Dissociation between activation of growth-related genes and mitogenic responses of neonatal vascular smooth muscle cells. AB - In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to alpha-thrombin. The molecular mechanism for this growth inhibition was investigated by looking at early transcriptional events in the cell cycle. Both thrombin and phorbol-12-myristate-13-acetate (PMA) induced mRNA for the c-myc oncogene; peak levels of expression were found 4-5 h after exposure to either agent. When thrombin and PMA were added together, c-myc expression was increased synergistically; down-regulation of protein kinase C suppressed induction of c-myc by thrombin. Thus, c-myc expression varied inversely with cell growth under these conditions. Thrombin and PMA also both induced expression of mRNA for the PDGF-A chain over 4-7h. As for c-myc, PMA and thrombin synergistically increased expression of the PDGF A-chain under conditions where PMA inhibits thrombin-induced DNA synthesis. Thus, mitogenesis and early growth-related gene expression was dissociated during PMA-mediated growth inhibition. PMID- 1755846 TI - Induction of DNA polymerase beta during proliferation of mitogen-stimulated human lymphocytes. AB - On induction of proliferation of human peripheral blood mononuclear cells by phytohemagglutinin treatment, DNA polymerase beta activity increases markedly before and during DNA replication. The increase of enzymatic activity seems to be well correlated with the increase of DNA polymerase beta mRNA, which is induced by enhanced expression of the DNA polymerase beta gene. These data suggest that DNA polymerase beta is involved in DNA repair, which is linked to replicative DNA synthesis, or directly in replicative DNA synthesis in normal proliferating cells. PMID- 1755847 TI - Multiple pathways of thrombin-induced platelet activation differentiated by desensitization and a thrombin exosite inhibitor. AB - Recently a thrombin receptor with a unique mechanism of activation was cloned from a megakaryocyte-like cell line (Vu et al., Cell 64:1057-1068, 1991). Thrombin cleaves a portion of this receptor creating a new N-terminus that acts as a "tethered-ligand" to activate the receptor. A thrombin receptor activating peptide (SFLLRNPNDKYEPF) homologous to the new N-terminus was shown to activate platelets. We synthesized this peptide and demonstrated that it desensitized platelets to activation by low concentrations of alpha-thrombin but not gamma thrombin. We also synthesized a thrombin exosite inhibitor (BMS 180742) that inhibited platelet aggregation induced by low, but not high, concentrations of alpha-thrombin. In contrast, a thrombin active site inhibitor, N alpha-(2 naphthylsulfonyl-glycyl)-D,L-amidinophenylalanylpiperi dide, competitively inhibited thrombin-induced platelet aggregation. We conclude that thrombin induced platelet activation is mediated by at least two pathways: one activated by low concentrations of alpha-thrombin and blocked by a thrombin exosite inhibitor that appears to be coupled to the "tethered-ligand" thrombin receptor, and another that is stimulated by higher concentrations of alpha-thrombin and by gamma-thrombin and does not require the thrombin exosite for activation. Both pathways are blocked by a thrombin active site inhibitor. PMID- 1755848 TI - Inter-molecular degradation of signal peptidase I in vitro. AB - Highly purified preparations of signal peptidase I (36 kDa) were found to undergo an apparent inter-autocatalytic degradation at 4 degrees C and 37 degrees C. The disappearance of the 36 kDa protein coincided with the stable appearance of a 31 kDa and a 5 kDa species. Amino-terminal sequencing of the 31 kDa product indicated a site specific cleavage following Ala38-Gln-Ala of signal peptidase I. The 31 kDa fragment was purified and shown to have 100-fold less activity than the native enzyme, with pre-maltose binding protein as a substrate. PMID- 1755849 TI - Enzyme chemistry of dithiohemiacetals: synthesis and characterization of S-D dithiomandeloylglutathione as an alternate substrate for glyoxalase I. AB - Both the D- and L-forms of S-dithiomandeloylglutathione (1) have been synthesized by a dithioester-interchange reaction between GSH and S-carboxy-methyl(D,L) dithiomandelate. Kinetic and product analysis studies indicate that yeast glyoxalase I efficiently catalyzes the stereoselective conversion of D-1 to GSH phenylglyoxal dithiohemiacetal (2), isolated as a disulfide adduct between 2 and a second molecule of GSH. This observation suggests that dithioester substrate analogues should be generally useful as mechanistic probes of enzyme catalyzed reactions involving thiohemiacetal intermediates. PMID- 1755850 TI - Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase. AB - We cloned and sequenced a full-length cDNA of human placental N acetylgalactosamine-6-sulfate sulfatase, the enzyme deficient in Morquio disease. The 2339-nucleotide sequence contained 1566 nucleotides which encoded a polypeptide of 522 amino acid residues. The deduced amino acid sequence was composed of a 26-amino acid N-terminal signal peptide and a mature polypeptide of 496 amino acid residues including two potential asparagine-linked glycosylation sites. Expression of the cDNA in transfected deficient fibroblasts resulted in higher production of this sulfatase activity than in untransfected deficient fibroblasts. The cDNA clone was hybridized to only a 2.3-kilobase species of RNA in human fibroblasts. The amino acid sequence of N-acetylgalactosamine-6-sulfate sulfatase showed a high degree of homology with those of other sulfatases such as human arylsulfatases A, B or C, glucosamine-6-sulfatase, iduronate-2-sulfatase and sea urchin arylsulfatase. PMID- 1755851 TI - Angiotensin II blocks ATP-sensitive K+ channels in porcine coronary artery smooth muscle cells. AB - ATP-sensitive K+ channels with small conductance (30 pS in symmetrical K(+)-rich solutions) in porcine coronary artery smooth muscle cells were highly active at physiological concentrations of Ca2+ (greater than 10(-4) M) even in the presence of physiological ATP levels, suggesting that these channels contribute to the generation of the resting membrane potential in vascular smooth muscle cells and their modulation is important in controlling vasomotor tone. Angiotensin II, applied from outside the membrane, blocked these channels in a concentration dependent manner. This would be expected to cause depolarization and result in vasoconstriction. PMID- 1755852 TI - Molecular cloning and nucleotide sequence of Streptomyces griseus trypsin gene. AB - Streptomyces griseus trypsin (E.C. 3.4.21.4) is one of the major extracellular proteinase, which is secreted by S. griseus. The gene encoding S. griseus trypsin was isolated from a S. griseus genomic library by using a synthetic oligonucleotide probe. Fragments containing the gene for S. griseus trypsin were characterized by hybridization and demonstration of proteolytic activity in S. lividans. Deduced amino acid sequence from the nucleotide sequence suggests that S. griseus trypsin is produced as a precursor, consisting of three portions; an amino-terminal pre sequence (32 amino acid residues), a pro sequence (4 residues), and the mature trypsin. The S. griseus trypsin consists of 223 amino acids with a computed molecular weight of 23,112. The existence of proline at the pro and mature junction suggests that the processing of S. griseus trypsin is non autocatalytic. PMID- 1755853 TI - Inhibition of the interaction between lipoproteins and amphotericin B by some delivery systems. AB - Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses. The clinical usefulness of the drug is limited by its high toxicity and several new less toxic formulations of AmB have been recently developed. In order to understand the mechanism of the decreases of toxicity caused by various new delivery systems, we have investigated by uv-visible spectroscopy the interaction of two of these formulations with human blood lipoproteins. The results were compared with those obtained with the commonly used pharmaceutical form of AmB (Fungizone). This study shows that AmB lipoprotein interaction is hindered when the drug is in a monomeric form and/or when it is included in phospholipid-surfactant micelles. In an in vivo study on mice it is shown here that AmB monomerized by surfactant is less toxic to animals than the same concentration of Fungizone, where the polyene is strongly aggregated. It may be concluded from the present study that the AmB species which is responsible for the in vivo toxicity is a complex of the antibiotic with the low density and the very low density blood lipoproteins and that hindering of this complex formation results in a decrease of AmB toxicity. PMID- 1755854 TI - Inhibition of farnesyl transferases from malignant and non-malignant cultured human lymphocytes by prenyl substrate analogues. AB - Cytosolic prenyl transferases from two human lymphoid tissue-derived cell lines, IM-9 and Molt-4 cells, are shown to isoprenylate recombinant p21H-ras. Isoprenylation was inhibited by an N-acetylated pentapeptide (N-Ac-Lys-Cys-Val Leu-Ser), c,t-farnesyl diphosphate, c,t,t-geranylgeranyl diphosphate, t,t,t geranylgeranyl diphosphate and a photolabile farnesyl diphosphate analogue. c,t Farnesyl and t,t,t-geranylgeranyl monophosphates were also effective inhibitors of the Molt-4 enzyme but not the IM-9 enzyme. PMID- 1755855 TI - Enzymatic properties of the protein encoded by newly cloned human alcohol dehydrogenase ADH6 gene. AB - Five non-allelic genes which encode five types of alcohol dehydrogenase subunits have been identified in humans. An additional gene (ADH6) and cDNA, whose coding sequences were not highly analogous to any of the known alcohol dehydrogenase subunits, were recently cloned (Yasunami et al., Proc. Natl. Acad. Sci. USA 88, 7610-7614, 1991). The full-length ADH6 cDNA was expressed in the E.coli expression system and in the in vitro translation system of rabbit reticulocytes. The protein produced had its isoelectric point at pH 8.6, optimum pH at pH 10, and a lower Km for benzylalcohol than for ethanol and propanol. These characteristics are compatible to the properties of mu- or sigma-alcohol dehydrogenase isozyme existing in human stomach, indicating that ADH6 gene encodes the mu- or sigma-alcohol dehydrogenase subunit. PMID- 1755856 TI - Non-essentiality of cysteine and histidine residues for the activity of human class PI glutathione S-transferase. AB - In order to examine the roles of cysteine and histidine residues in the activity of human class Pi glutathione S-transferase (GST pi), site-directed mutagenesis was used to replace each of the four cysteine residues (at positions 14, 47, 101 and 169) with serine and each of the two histidine residues (at positions 71 and 162) with asparagine using a cDNA for the enzyme (Kano, T. et al. (1987) Cancer Res., 47, 5626-5630) and an E. coli expression system. The replacements of Cys101, Cys169, His71 and His162 did not affect the GSH-conjugating activity toward 1-chloro-2,4-dinitrobenzene and ethacrynic acid. On the other hand, the activities were partly decreased by the replacements of Cys47 and Cys14. These results indicated that the cysteine and histidine residues in GST pi are not essential for the catalytic activity, although Cys47 and Cys14 may contribute to some extent to the catalytic efficiency. PMID- 1755857 TI - Alzheimer disease paired helical filament core structures contain glycolipid. AB - The core structures of sodium dodecyl sulfate extracted, pronase digested paired helical filaments of Alzheimer disease were solubilized by heating in dimethyl sulfoxide. Electron microscopy revealed that after heating in dimethyl sulfoxide, intact paired helical filaments were no longer present in the dimethyl sulfoxide soluble fractions or in the insoluble lipofuscin-containing fractions. Enzyme linked immunosorbent assays of the various fractions with the monospecific antibody A128 to paired helical filaments demonstrated 96% of the immunoreactivity to be in the dimethyl sulfoxide soluble fraction, and only 4% in the dimethyl sulfoxide insoluble fractions. Lyophilization of the dimethyl sulfoxide soluble supernatant and resuspension in water failed to reassociate the paired helical filaments, but did result in an insoluble precipitate. Analysis of the dimethyl sulfoxide solubilized paired helical filament fraction by nuclear magnetic resonance revealed it to be composed of glycolipid in a form that was distinct from similar fractions isolated from normal aged control brains. The aggregation of an altered glycolipid to form paired helical filaments in Alzheimer disease could explain their insolubility. PMID- 1755858 TI - Simultaneous measurement of Ca2+ transients and of membrane depolarizations in synaptosomes. AB - Calcium and membrane potential sensitive dyes have been widely used to study the biochemical effects of the intracellular calcium concentration and of the membrane potential on diverse biochemical processes. However, due to the discontinuous measurement techniques applied, it was until now impossible to get an insight into the sequence and dynamics of the induced biological reactions. In order to study the relationship between the intracellular calcium concentration and the membrane potential, an apparatus was developed capable of measuring both biological processes simultaneously. Potassium chloride induced changes of the synaptosomal membrane potential and of the intracellular calcium concentration are presented. PMID- 1755859 TI - Changes in binding activity of luteinizing hormone receptors by site directed mutagenesis of potential glycosylation sites. AB - Site directed mutagenesis of the rat ovarian luteinizing hormone (LH) receptor cDNA was performed at each of the six potential N-linked glycosylation sites to determine the effect of putative carbohydrate chains on the activity of the membrane receptor. The conversion of Asn173 to Gln resulted in the total loss of hormone binding to the surface of the transfected cell. Mutant receptors synthesized with substitutions at the remaining potential N-linked glycosylation positions of 77, 152, 269, 277 and 291 revealed no significant change in the hormone affinity. However Asn77Gln and Asn152Gln exhibited significant decreases (approximately 80%) in the number of high affinity hormone binding sites. The changes in hormone binding activity upon elimination of the potential glycosylation sites at 77, 152 and 173 indicate the presence of functional carbohydrate chains at these positions in the rat ovarian LH/hCG receptor. PMID- 1755860 TI - The modulation of growth by HMBA in PKC overproducing HT29 colon cancer cells. AB - To examine whether protein kinase C (PKC) plays a role in mediating growth inhibitory effects of hexamethylene bisacetamide (HMBA) we compared a control H29 colon cancer cell line to a derivative, HT29-PKC7, that overexpresses high levels of PKC beta 1. We found that although HMBA markedly inhibited the growth of the control cells, no inhibition was seen with the HT29-PKC7 cells. On the other hand the tumor promoter 12-0-tetradecanoyl-phorbol-13 acetate inhibited the growth of HT29-PKC7 cells, but no inhibition was seen with the control cells. Maximum inhibition of the growth of both cell lines was obtained by combined treatment with HMBA and TPA. These results may be relevant to the use of HMBA in combination with other agents in the therapy of specific cancers. PMID- 1755861 TI - Inhibition and enhancement of eukaryotic gene expression by potential non-B DNA sequences. AB - In a transient or constitutive expression assay we have examined the effect of non-B DNA sequences d(CA)40 and d(CAAAAATGCC)n on gene expression in eukaryotic cells. These sequences were cloned adjacent to the weak eukaryotic promoter (CGTATTTATTTG) and located upstream from the coding sequence of galactokinase enzyme. Recombinants were micro-injected in cultured cells (Chinese hamster fibroblasts R1610, mutant gal-K-) and expression levels have been determined. The alternating purine-pyrimidine tract found in d(CA)40 able to assume the Z-DNA conformation shows an inhibitory effect on gene expression. In addition, our results suggest a new potential role of Z-DNA motifs in vivo to stimulate recombination. The sequences d(CAAAAATGCC)n able to adopt another non-B structure, corresponding to curved (or bended) helix conformation, strongly enhance gene expression and this enhancement depends on sequence redundancy. PMID- 1755862 TI - Effects of epidermal growth factor and calcium omission on cholecystokinin stimulated Cl- conductance in rat pancreatic zymogen granules. AB - Evidence suggests that cholecystokinin-octapeptide (CCK-8)-induced activation of a Cl- conductance in the membrane of zymogen granules (ZG) is closely related to pancreatic enzyme secretion. Following stimulation of isolated pancreatic acinar cells with increasing concentrations of CCK-8, the Cl- conductance in the ZG from these acini increased, reached a maximum of 40 +/- 7% above basal Cl- conductance at 10(-12) M CCK-8, and then decreased at CCK-8 concentrations higher than 10(-9) M to a level comparable to the basal Cl- conductance. We had interpreted the inhibitory action of high CCK-8 concentrations to be due to the generation of high concentrations of diacylglycerol and/or its metabolites by an "overstimulation" of phospholipase C at supramaximal CCK-8 concentrations. We now show that EGF abolishes the downstroke of the dose response curve for CCK-8 induced ZG Cl- conductance and shifts the stimulatory response to higher CCK-8 concentrations. Similarly in a nominally "Ca(2+)-free buffer" (free [Ca2+] approximately 0.2 nM), stimulated Cl- conductance at 10(-12) M CCK-8 is nearly abolished and the decreased Cl- conductance at 10(-8) M CCK-8 is increased to the level of maximal stimulation at 10(-12) M CCK-8. We conclude that both EGF and low [Ca2+] affect CCK-8-induced ZG Cl- conductance by decreasing phospholipase C activity. PMID- 1755863 TI - Concept of VNTR alleles: comparison of apolipoprotein B 3' hypervariable region genotyping results obtained by three methods. AB - In this study the apolipoprotein B 3' hypervariable region genotyping results obtained by three polymerase chain reaction and gel electrophoresis -based methods were compared. In 43 subjects of Finnish origin three individuals had each one allele (3.5%) which exhibited different migration when the apolipoprotein B 3' hypervariable region amplification products were separated on nondenaturing polyacrylamide gel electrophoresis as compared to agarose or denaturing polyacrylamide gels. Segregation of the variantly migrating alleles could be demonstrated in pedigrees suggesting that the variation might be due to differences in the DNA sequence among alleles with same apparent size on agarose or denaturing polyacrylamide gels. PMID- 1755864 TI - Identification of the trypsin-like activity in commercial preparations of eel acetylcholinesterase. AB - Electricus electrophorus acetylcholinesterase (AChE, EC 3.1.1.7) is reported to possess a trypsin-like activity. We found that purification of AChE removes over 99% of this protease activity, which resides in a single 25 kDa protein with an N terminal sequence identical to bovine pancreatic trypsin. Digests of neuropeptides using purified eel AChE or bovine pancreatic trypsin gave identical peptide maps. These results indicate that the commercial preparation of eel AChE is contaminated by a trypsin, which is difficult to remove completely during AChE purification. PMID- 1755865 TI - Endogenous nitric oxide modulates morphine-induced constipation. AB - Administration of morphine in mice causes inhibition of the gastrointestinal transit of a charcoal meal. Morphine-induced constipation in mice seems to depend predominantly on action(s) on the central nervous system since N-methyl morphine, a quaternary derivative, inhibits intestinal transit only when administered intracerebroventricularly (i.c.v.). L- but not D-arginine, given intraperitoneally, reversed the constipation induced by both morphine and its quaternary analogue. L-arginine was ineffective when given i.c.v. and did not reverse atropine-induced constipation. These results suggest that L-arginine preferentially modulates opioid-induced constipation through a stereospecific and peripheral action(s). It is possible that the effect of L-arginine is achieved by increasing the amount of nitric oxide released by non-adrenergic, non-cholinergic nerves in the gut. Thus, L-arginine may represent a useful agent for the treatment of undesirable constipation associated with the use of narcotic analgesics. PMID- 1755866 TI - Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. AB - Extracellular proteolysis is believed to be an essential component of the angiogenic process. The effects of VEGF, a recently described angiogenic factor, were assessed on PA activity and PA and PAI-1 mRNA levels in microvascular endothelial cells. u-PA and t-PA activity were increased by VEGF in a dose dependent manner, with maximal induction at 30 ng/ml. u-PA and t-PA mRNAs were increased 7.5- and 8-fold respectively after 15 hours, and PAI-1 mRNA 4.5-fold after 4 hours exposure to VEGF. At equimolar concentrations (0.5 nM), VEGF was a more potent inducer of t-PA mRNA than bFGF, while bFGF was a more potent inducer of u-PA and PAI-1 mRNAs. In addition, VEGF induced u-PA and PAI-1 mRNAs with kinetics similar to those previously demonstrated for bFGF. These results demonstrate the regulation of PA and PAI-1 production by VEGF in microvascular endothelial cells and are in accord with the hypothesis that extracellular proteolysis, appropriately balanced by protease inhibitors, is required for normal capillary morphogenesis. PMID- 1755867 TI - Hydrogen bonds involving sulfur atoms in proteins. AB - Intrachain hydrogen bonds are a hallmark of globular proteins. Traditionally, these involve oxygen and nitrogen atoms. The electronic structure of sulfur is compatible with hydrogen bond formation as well. We surveyed a set of 85 high resolution protein structures in order to evaluate the prevalence and geometry of sulfur-containing hydrogen bonds. This information should be of interest to experimentalists and theoreticians interested in protein structure and protein engineering. PMID- 1755868 TI - Ocular effects of the endothelins. Abundant peptides in the eye. AB - Endothelins (ETs) are a family of potent vasoactive peptides present in the eye. In the rabbit eye, both ET-1 and ET-3 are present in high concentrations in the iris and ciliary body and in lower concentrations elsewhere. Forty-eight hours after injection of 2.5 micrograms of ET-1 and ET-3 into the anterior vitreous of conscious rabbits, intraocular pressure was reduced by 43% and 45%, respectively, and did not return to normal for at least 5 days. The decrease in intraocular pressure was not due to increased aqueous outflow and was not prevented by pretreatment with indomethacin. Injection of either ET-1 or ET-3 (2.5 to 10 micrograms) into the anterior chamber or posterior vitreous cavity resulted in marked vasoconstriction, which was initiated within seconds and persisted for greater than 4 hours. Both endothelins potently constricted the pupil when added to freshly excised rabbit anterior segments. Endothelins are therefore potential participants in the local regulation of intraocular pressure, ocular blood vessel tone, and iris smooth muscle tone and may be important mediators in ocular pathologic conditions. Endothelins at pharmacologic doses may be useful in the control of intraocular pressure or blood flow. PMID- 1755869 TI - Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. AB - Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products. PMID- 1755870 TI - Perceptions of weight and attitudes toward eating in early adolescent girls. AB - Sixth grade girls (n = 206) responded to questions about their weight, body image, dieting practices, and attitudes toward weight and eating. Results suggested that feeling too fat and wishing to lose weight were becoming normative for young adolescent girls in that the majority of girls wished to weigh less and said that they dieted at least occasionally. For most girls, weight concerns had emerged between the ages of 9 to 11. A sizeable proportion of girls seemed to have adopted a "dieting mentality," claiming to be avoiding fat, counting calories, thinking excessively about food, feeling guilty after eating and overeating, and exercising to lose weight. Such practices were common even among girls who did not describe themselves as overweight or who were satisfied with their appearance. The emergence of these attitudes and behaviors at increasingly younger ages is of grave concern, as several of them are risk factors for the development of serious eating disorders. PMID- 1755871 TI - Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations. AB - Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported. PMID- 1755872 TI - Endometriosis: will the real natural history please stand up? PMID- 1755873 TI - Levels of sexual activity among adolescent males in the United States. AB - Although three-fifths of adolescent males aged 15-19 say they have had sexual intercourse, analyses of data from the 1988 National Survey of Adolescent Males indicate that their level of sexual activity is relatively moderate. The data show that among sexually experienced young men the mean number of partners in the last 12 months is 1.9, and the mean frequency of intercourse in the last four weeks is 2.7 times. Black males have had more partners than white or Hispanic males; however, after the number of years since first intercourse are controlled for, these differences disappear. On average, sexually experienced youth spent six out of the last 12 months with no sexual partner, and only 21 percent of sexually active males had more than one partner in any month in the last year. Comparisons with 1979 data suggest that proportionately more adolescents were sexually experienced in 1988, but fewer non-black males had first intercourse before their 15th birthday. The number of partners since first intercourse and in the past four weeks appears to have decreased, as has the frequency of intercourse in the last four weeks. PMID- 1755874 TI - AAEM minimonograph #36: basic concepts of electricity and electronics in clinical electromyography. AB - Fundamental principles of electricity provide a basis for understanding the design and operation of electromyography equipment. An intuitive and quantitative explanation of charge, voltage, current, and impedance provides an introduction to the concepts of resistance, capacitance, and input impedance. These concepts form the basis for discussion of filters, amplifiers, electrodes, digital electronics, stimulators, and patient safety. The monograph assumes no specialized training in engineering or mathematics. The topics are discussed at an introductory level to provide understanding for readers with no electronics background and intuitive insight for more experienced readers. PMID- 1755875 TI - Cancer risk and behavior change. PMID- 1755876 TI - Adolescent smokers seen in general practice: health, lifestyle, physical measurements, and response to antismoking advice. AB - OBJECTIVE: To compare physical, lifestyle, and health characteristics of adolescent smokers and non-smokers and their initial response to anti-smoking counselling. DESIGN: Adolescents aged 13, 15, and 17 years were identified from age-sex registers and invited by letter for a general practice health check. SETTING: Three general practices in the MRC general practice research framework. MAIN OUTCOME MEASURES: Blood pressure, body mass index, saliva cotinine concentration, peak flow rate, alcohol consumption, exercise, duration of sleep, and stated persistent health problems. RESULTS: 73% of the adolescents (491) attended for the health check. A total of 68 (14%) were regular smokers. By age 17 those who smoked regularly had a significantly lower systolic blood pressure than those who had never smoked regularly (by 6 mm Hg; p = 0.025) despite a significantly higher body mass index (by 1.5; p <0.001) [corrected]. Cotinine concentrations increased with smoking exposure, from 0.7 ng/ml when no family member smoked to 155 ng/ml in active smokers of six or more cigarettes a week. Significantly more regular smokers than never regular smokers drank greater than or equal to 8 g alcohol a day (chi 2 = 15.2 adjusted for age and sex p less than 0.001); regular smokers exercised less (1.0 hrs/week in boys and 0.8 hrs/week in girls v 3.4 hrs/week in boys and 2.2 hrs/week in girls; p less than 0.001) and slept less (8.0 hrs/night v 8.5 hrs/night at age 17; p less than 0.005). Persistent health problems, mostly asthma or allergic symptoms, were reported by 25% (17/68) of the smokers and 16% (60/381) of the non-smokers. Of the smokers given counselling, 60% (26/43) made an agreement with the practice doctor or nurse to give up smoking. CONCLUSION: General practice is an appropriate setting for adolescents to receive advice on healthy lifestyle, which should not focus solely on smoking. PMID- 1755877 TI - Gender recognition from speech. Part II: Fine analysis. AB - The purpose of this research was to investigate the potential effectiveness of digital speech processing and pattern recognition techniques for the automatic recognition of gender from speech. In part I Coarse Analysis [K. Wu and D. G. Childers, J. Acoust. Soc. Am. 90, 1828-1840 (1991)] various feature vectors and distance measures were examined to determine their appropriateness for recognizing a speaker's gender from vowels, unvoiced fricatives, and voiced fricatives. One recognition scheme based on feature vectors extracted from vowels achieved 100% correct recognition of the speaker's gender using a database of 52 speakers (27 male and 25 female). In this paper a detailed, fine analysis of the characteristics of vowels is performed, including formant frequencies, bandwidths, and amplitudes, as well as speaker fundamental frequency of voicing. The fine analysis used a pitch synchronous closed-phase analysis technique. Detailed formant features, including frequencies, bandwidths, and amplitudes, were extracted by a closed-phase weighted recursive least-squares method that employed a variable forgetting factor, i.e., WRLS-VFF. The electroglottograph signal was used to locate the closed-phase portion of the speech signal. A two way statistical analysis of variance (ANOVA) was performed to test the differences between gender features. The relative importance of grouped vowel features was evaluated by a pattern recognition approach. Numerous interesting results were obtained, including the fact that the second formant frequency was a slightly better recognizer of gender than fundamental frequency, giving 98.1% versus 96.2% correct recognition, respectively. The statistical tests indicated that the spectra for female speakers had a steeper slope (or tilt) than that for males. The results suggest that redundant gender information was imbedded in the fundamental frequency and vocal tract resonance characteristics. The feature vectors for female voices were observed to have higher within-group variations than those for male voices. The data in this study were also used to replicate portions of the Peterson and Barney [J. Acoust. Soc. Am. 24, 175-184 (1952)] study of vowels for male and female speakers. PMID- 1755878 TI - Combination of binaural information across frequency bands. AB - Perceptual grouping of the frequency components from a source into a single auditory object is needed when localizing a complex sound in an environment where other sounds are also present. Two acoustic regularities that might allow for such grouping are a harmonic relation among the components and a commonality of their spatial positions. The utility of these cues was examined in a forced choice psychophysical task by measuring sensitivity to interaural differences of time (IDT) for low-frequency stimuli presented via earphones. In the first experiment, stimuli were composed of either one, two, or three frequencies. A signal detection analysis used to predict the effects of combining information across frequencies found summation to be optimal, regardless of the harmonicity of the complex. A second experiment presented two-frequency complexes in which one tone, the target, contained the IDT to be detected while the other, the distractor, was constant across all three intervals of the forced choice. For inharmonic complexes, performance for the target-distractor combinations was equivalent to that found for targets presented alone, suggesting segregation of the targets and distractors into separate auditory objects. However, for harmonic target-distractor combinations, performance was diminished. A signal detection analysis of these data supports the idea that for purposes of lateralization, the interaural information in the targets and distractors was combined into a variance-weighted value, even though it meant a lowering of performance. Thus it seems that for the grouping of complex acoustic stimuli in space, harmonic structure is more important than commonality of spatial position. PMID- 1755879 TI - Brain aging and Alzheimer's disease, "wear and tear" versus "use it or lose it". AB - In organs other than the brain, cell activation seems to increase "wear and tear," e.g., by increased free-radical formation, and so to cause an increased rate of aging. However, activation of nerve cells within the physiological range seems to lead to maintenance of neurons during aging and in Alzheimer's disease, possibly by preferentially stimulating the action of protective mechanisms such as DNA repair. This "use it or lose it" principle might explain why certain neurons degenerate in aging or Alzheimer's disease while others do not, and why recovery of various neuronal systems during aging has been obtained by restoration of the missing stimulus. Consequently, neuronal activation might provide a means of prolonging its optimal function for the full length of our natural life span. PMID- 1755880 TI - Blood lactate and mixed venous-arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass surgery. AB - Conventional indices of tissue perfusion after surgery involving cardiopulmonary bypass (CPB) may not accurately reflect disordered cell metabolism. Venous hypercarbia leading to an increased veno-arterial difference in CO2 tensions (V aCO2 gradient) has been shown to reflect critical reductions in systemic and pulmonary blood flow that occur during cardiorespiratory arrest and septic shock. We therefore measured plasma lactate levels and V-aCO2 gradients in 10 patients (mean age 57.2 years) following CPB and compared them with conventional indices of tissue perfusion. Plasma lactate levels, cardiac index (CI) and oxygen uptake (VO2) all increased significantly (p less than 0.05 vs baseline levels) up to 3 h following surgery. Oxygen delivery (DO2) did not change. Plasma lactate levels correlated significantly with CI (r = 0.47, p less than 0.01). V-aCO2 fell significantly with time (p less than 0.01 vs baseline). There was an inverse relationship between V-aCO2 and cardiac index and V-aCO2 and lactate (r = -0.37, p less than 0.05; r = -0.3, p less than 0.05 respectively). We conclude that blood lactate, CI and VO2 increase progressively following CPB. An increase in lactate was associated with a decrease in V-aCO2. An increase in V-aCO2 was not therefore associated with evidence of inadequate tissue perfusion as indicated by an increased blood lactate concentration. PMID- 1755881 TI - The role of arthroscopic debridement after anterior cruciate ligament reconstruction. AB - This retrospective study included 55 patients who had prior anterior cruciate ligament (ACL) reconstruction; 30 made up the experimental group who had arthroscopic debridement of impinging soft tissue and 25, who did not have a second-look arthroscopy, were used as controls. Impinging tissue was not necessarily the primary reason for arthroscopy in the experimental group. Only nine patients (30%) were debrided solely because of anterior symptoms suggestive of soft tissue impingement; 16 (53%) underwent arthroscopy primarily to assess meniscal repairs; five (17%) were done in conjunction with hardware removal. Both groups were evaluated for pain, crepitation, and anterior laxity at three specific times. Debridement reduced crepitation from 35% to 8% in patients with moderate crepitus, and from 50% to 38% in patients with mild symptoms. The percentage of patients without crepitation increased from 15% to 54% by final follow-up. Predebridement, 14% of patients had moderate pain, and 53% mild pain. By final follow-up, 38% had mild pain and 62% were pain free. Patients benefitted from debridement regardless of method of ACL reconstruction. Arthroscopic debridement did not increase anterior knee translation. Both groups gained extension and had improved activity levels with the passage of time from ACL surgery. PMID- 1755882 TI - Anterior cruciate ligament reconstruction without drill holes. AB - Anterior cruciate ligament (ACL) reconstruction in adolescents with open physes remains a difficult problem for the orthopedic surgeon, especially in view of growing teenage participation in contact sports. Traditionally, treatment of ACL tears in adolescents has been conservative; the patient is advised to delay surgery up to several years for fear of damaging physes by drilling holes across them. Unfortunately, this waiting period may inflict irreparable knee damage. This paper suggests an ACL reconstruction technique that utilizes no drill holes, thus causing no harm to physes or other essential knee structures. A graft consisting of semitendinosus and gracilis (SG) tendons is passed under the anterior horn of the medial meniscus through the knee joint, then brought out through the posterior capsule and secured to the lateral femoral metaphysis. The graft is augmented with an iliotibial band tenodesis. Designed primarily but not exclusively for teenagers with open physes, the procedure has produced encouraging results thus far in a small series. PMID- 1755883 TI - Role of arthroscopy in osteoarthritis of the knee. AB - We compared arthroscopic partial menisectomy with limited debridement versus arthroscopic abrasion arthroplasty in patients with osteoarthritis. Group I consisted of 131 knees in 131 patients treated by partial meniscectomy and debridement of loose articular cartilage or removal of loose bodies. All patients had grade 3 or 4 chondromalacia in the affected compartment. The patients were followed for a mean of 3 +/- 1 years. Group II consisted of 28 knees in 28 patients treated by debridement with abrasion arthroplasty of exposed bone. The mean age of this group of patients was 63 years and they were followed for a mean of 3.8 years. The Group I patients noted 80% improvement by 1 year but this fell to 67% by 5 years after meniscectomy. Overall, 104 were improved, 16 unchanged, and 15 worse at the time of last evaluation compared to their preoperative status. In the Group II patients, 11 were improved, 8 unchanged, and 9 worse. Fifty percent of Group II subsequently underwent a total knee arthroplasty for salvage at a mean of 3 years following the abrasion procedure. Abrasion arthroplasty appears to offer little benefit over partial meniscectomy and debridement in the degenerative knee. Results of abrasion arthroplasty are unpredictable. PMID- 1755884 TI - The effect of intra-articular instillation of bupivacaine on postarthroscopic morbidity: a placebo-controlled, double-blind trial. AB - Forty patients undergoing diagnostic arthroscopy of the knee were included in a randomized double-blind study to investigate the effect of bupivacaine on postarthroscopic morbidity. The arthroscopies were performed under local anesthesia using 1% lidocaine with adrenaline. At the conclusion of the arthroscopic examination, 10 ml 0.5% bupivacaine with adrenaline or 10 ml placebo was instilled and left in the joint cavity. The two groups of patients were compared with regard to postarthroscopic duration of the anesthesia, degree of postarthroscopic pain, number of analgesic tablets taken, need for crutches or other walking aids, and days away from work. There was no difference between the patients receiving bupivacaine and patients receiving placebo for any of the parameters investigated. PMID- 1755885 TI - A new technique of harvesting patellar tendon autografts for anterior cruciate ligament reconstruction. AB - A new surgical technique to uniformly harvest the middle one-third of the patellar tendon for anterior cruciate ligament reconstruction is described. The technique uses a guide system of 8 templates of varying widths to guide the saw cuts and "collared," depth-controlled saw blades and drill bits to produce a standard cutting and drilling depth. This kind of template system lessens the risks of graft harvesting complications such as patella fracture, bone graft fragmentation, suture pull out, and judgment errors pertaining to graft depth, length, or width. The Patellar Tendon Graft Guide was used to obtain a patellar tendon graft in 65 patients. Fifty-nine arthroscopic-assisted and 6 open anterior cruciate ligament reconstructions were performed. Of the 65 grafts harvested, 63 consistently demonstrated bone portions 20 mm in length, 7 mm in depth, and a width corresponding to the template chosen (usually 10 mm). Two grafts supposed to be 10 mm in width turned out to be 9 mm in width because of a technique related problem. PMID- 1755886 TI - The value of high resolution CT in the diagnosis of meniscal lesions of the knee. AB - We report on 50 patients who had meniscal pathology and were given computed tomographic (CT) scans. Our diagnostic accuracy was approximately 92%. We believe that CT is a good method of screening these patients prior to using a much more expensive method, such as magnetic resonance imaging or diagnostic arthroscopy. PMID- 1755887 TI - Simple bone cyst of the distal tibia: a case for ankle arthroscopy. AB - Intraarticular ankle anatomy may be better visualized arthroscopically than with an arthrotomy. Ankle arthroscopy was crucial in locating a simple bone cyst and directing therapeutic curettage of the lesion. PMID- 1755888 TI - A fracture of the intercondylar eminence of the tibia treated by arthroscopic fixation. AB - A fracture of the intercondylar eminence of the tibia in a 27-year-old woman was treated arthroscopically, using the Acufex (Acufex Microsurgical, Inc., U.S.A.) drill guide system for anterior cruciate ligament reconstructions. An adequate fixation was achieved, and an arthrotomy was avoided. The patient recovered quickly, with no residual symptoms. We recommend performing an arthroscopy in every patient with a fracture of the intercondylar eminence. The fracture can be treated arthroscopically by rigid internal fixation, while at the same time treating possible associated lesions. PMID- 1755889 TI - A solution for arthroscope misting. AB - A prospective study was undertaken to compare the incidence of arthroscope eyepiece misting in two groups of patients. In one group the irrigation fluid was at room temperature and in the other group the fluid was warmed to body temperature. Arthroscope eyepiece misting was eliminated when irrigation fluid at body temperature was used. PMID- 1755890 TI - Arthroscopy--an orthopaedic surgical subspecialty or a technique? PMID- 1755891 TI - Lasers in arthroscopic surgery. PMID- 1755892 TI - Endoscopic release of carpal ligaments. PMID- 1755893 TI - Electrocautery. PMID- 1755894 TI - Knee arthroscopy and local anesthesia. PMID- 1755895 TI - [Interventional angiography in the ENT field]. AB - Development of new micro catheters and digital technique of angiography today allows a superselective angiography of small vessels of the external carotid artery. Therapeutical and diagnostical possibilities for ENT will be discussed. PMID- 1755896 TI - [Protection for noise-induced hearing loss using active hearing protection systems]. AB - Though noise induced hearing loss is no longer the most frequent occupational disease in the Federal Republic of Germany, the environmental pollution by the product "noise" in our technical and industrialized world has not been reduced. On the contrary, the situation is worsened by the rising influence of leisure noise. To avoid occupational hearing loss, the "Noise Injury Prevention Code" issued by the insurers would demand wearing personal ear protection, e.g. ear plugs, if ambient noise levels are above 85 dB(A). But there are working places in which such equipment would have precisely the adverse effect, because one of the reasons for possible damage to hearing is radio communication. In military aircraft cockpits for example noise exposure measurements showed ambient noise levels above 90 dB(A) during regular flight service nearly all the time. To be able to understand radio traffic in spite of the noisy environment, the headphone volume must be raised above the noise of the engines. The use of ear plugs can only be of limited value. Whereas pilots with normal hearing show only little impairment of speech intelligibility, those with noise-induced hearing losses show substantial impairment that varies in proportion to their hearing loss. Communication abilities may be drastically reduced which may compromise the reliability of radio traffic. To avoid compromising air security one has to demand a noise protection system which allows to reduce ambient noise levels without disturbing speech intelligibility in the inevitable radio communication. Nowadays active noise cancelling (ANC) systems by electronic compensation in different ways provide effective protection against noise induced hearing loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755897 TI - [Experiences with high-frequency hearing tests in the selection of personnel for noise occupations]. AB - A total of 181 persons aged between 16 and 18 were checked fully audiometrically (conventional and high-frequency audiogram). Dates of history about hereditary hearing damage, own ear diseases, noise exposure during frequent visits to discothecs or usage of Walkman etc. were ascertained by questionnaires. The evaluation of the results was carried out with the help of discrimination analysis allowing a multi-dimensional classification. As a result there could be made a sure discrimination analytic separation in persons with ear diseases during their childhood, when the high frequencies from 10 to 15 kHz were taken in. Thus the damage of the inner ear was to be found mainly on the base of the cochlea. Also in cases of hereditary influence there was to be seen a clear deminution in the high frequency area. The group of persons, who regularly went to discos (more than three times a month) as well as the group often using Walkman revealed a sure separation, when the high frequencies above 8 kHz were considered in the calculation. Altogether there could be seen an early damage more clearly in the high frequency area after ear diseases in childhood as well as a result of sound overloading than in conventional hearing area. PMID- 1755898 TI - [Functional dysphonia following cervical spine injuries]. AB - After a head or a cervical injury dysphonia and its accompanying globus syndrome are often ignored, even if the existence of these traumatic sequelae are repeatedly reported. Till now there is no coherent idea about their pathogenesis, wherefore in the individual case wide differences exist in the diagnosis, treatment and in the expert opinion. It could be shown in this paper, that a posttraumatic dysphonia, due to a minor trauma, is a well defined disease with an uniform pathogenesis. The diagnosis results from the typical anamnesis of the accident, from the prove of the functional dysphonia and last not least from the prove of a functional deficit of the cervical spine, especially in the height of C 2/3. The right diagnosis allows a causal treatment and enables a just expert opinion. PMID- 1755899 TI - [Vertebrogenic dysphagia in diffuse idiopathic skeletal hyperostosis (Forestier's disease)]. AB - Swallowing disorders can be caused by morphologic changes of the cervical spine such as diffuse idiopathic skeletal hyperostosis. The paper describes current concepts of this clinical entity also known as Forestier's disease. The symptomatology, radiographic features and treatment are discussed. Particular interest is focused on dysphagia. The diagnosis is exclusively radiographic. Cervical osteophytes can be detected in 20-30% of the population in asymptomatic patients. Therefore, the attribution of the presence of osteophytic deformities of the barium column to dysphagia should not be made unless objective evidence of impairment of pharyngeal function such as abnormal posterior pharyngeal wall motion is proven by dynamic imaging means. The therapeutic approach depends on the extent of dysphagic complaints. Indications for surgery are failure to respond to conservative management (anti-inflammatory drugs, concomitant antibiotics, dietary nutrition). The anterolateral extrapharyngeal approach is commonly preferred. PMID- 1755900 TI - [Frequency dependence of the SISI test.(short increment sensitivity index). Clinical examples]. AB - Experimental data on the influence of test frequency on the SISI-score are controversial. Comparability is limited by the diversity of experimental conditions. In a series of cases of pancochlear sudden hearing loss SISI-scores at 0.5 kHz and 3 kHz were compared. Some examples show that the sensitivity of the SISI-test at 0.5 kHz is much lower to that at 3 kHz. Low SISI-scores, of little evidence per se, have to be considered very critically in the low pitch range. PMID- 1755901 TI - [In-situ measurement as necessary component of hearing aid fitting]. AB - The most important ear simulator measurement methods like 2-cm3 coupler, Zwislocki coupler, KEMAR were outlined. The disadvantages of these measurement methods were listed. So the ear simulator methods not take into account the individual anatomic conditions like the residual volume between the earmold and the eardrum, the impedance of the middle ear and the outer ear resonance. The influence on the sound pressure level in front of the eardrum caused by modifications of ear molds as another very important part of the hearing aid fitting, can not be assessed by measurement far away from the patients ear. All these individually varying factors only can be integrated into the hearing aid fitting by real ear measurement in front of the eardrum. PMID- 1755902 TI - [A new implant system in head and neck surgery]. AB - Defects in the head and neck region following extensive tumor removal are sometimes difficult to reconstruct by local or free flaps. An epithesis is a recommended alternative in defects of the ear, the nose or the orbital region. Nevertheless problems may arise in the appropriate fixation of the epithesis. With the intermobile-cylinder-implant-system (IMZ), the epithesis is firmly fixed by means of osseointegration of the implants and an abutment in the area of the defect. The various steps of the operation and clinical applications are presented. PMID- 1755903 TI - [Immunological reactions against preserved tracheal transplants? Studies on inbred rat strains]. AB - To determine whether chemical (cialit, merthiolate, alcohol, formaldehyde solution) preserved tracheal segments maintain immunogenicity we performed systematic transplantation-immunological investigations using in vivo-, in vitro- and immunohistological tests. In contrast to other authors no indication of residual antigenicity was found. The survival rates after orthotopic grafting of preserved tracheal segments were shortened. This seems due to the loss of the mucociliary clearance, caused by chemical induced damages in the tracheal mucosa. PMID- 1755904 TI - [Evaluation of transitory evoked otoacoustic emissions in children with impaired tubal ventilation]. AB - Transient evoked otoacoustic emission (TEOAE) has proven to be a useful clinical screening test for auditory dysfunction. Problems concerning the evaluation are mainly due to irregularities of the physiological middle ear functions. In this study different degrees of middle ear alterations of otherwise normal-hearing children were quantified by means of tympanometry, otoscopy and pure-tone audiometry and then related to the results of TEOAE registration which were classified by the coefficient of the crosscorrelation and the frequency response spectrum. Data were obtained from 266 ears of 148 children between the age of 3 months and 11 years. The results indicate that even slight middle ear irregularities, e.g. negative pressure between -50 and -100 mm H2O, can reduce the rate of successfully recorded TEOAE from 95% (70/74) in the normal group to 78% (34/47). When children displayed a tympanogramm with no observable peak, a successful registration of TEOAE was possible in only 12% (n = 34) of the cases. Such results are related to serous or mucoid effusions which probably prevent a transmission of the emission from the cochlea to the meatus. In analysing the relation between conductive losses in pure-tone audiometry and TEOAE it was demonstrated that no TEOAE could be recorded in ears with a conductive loss above 20 dB HL. Where the conductive loss is smaller than 20 dB HL it is not possible to predict whether a reliable emission can be recorded or not. This study emphasizes the need to reexamine children who do not show positive emissions connected with middle ear imbalances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1755905 TI - [Management of cochlear implants in children--methods and results]. AB - Selection criteria, basic principles of auditory training, development of an auditory test battery for children and results of 15 children between 4 and 14 years are presented and discussed. To summarize, results range from acoustic attention to tones and sounds and recognition of environmental sounds to the use of supra-segmental and segmental features of speech. Some children are able to recognize words and phrases from a closed list. One of the children has postlingual deafness and has had also a very short duration of deafness before implantation. This child shows better results than the pre and perilingually deaf children. Because of the fact that the patient group is small and there are also many intervening variables like age, duration of deafness and use of two different test instruments, it is difficult to find a relationship between the results and all other variables. The auditory test battery for children, which consists of seven subtests, measuring acoustic orientation and auditory speech perception on different linguistic levels, is much more suitable for the evaluation of auditory performance for this age group than the auditory test battery for adults (Eisenwort and Burian 1988). PMID- 1755906 TI - [Sudden deafness. A clinical analysis with special reference to tympanoscopy]. AB - From a total of 720 patients with acute deafness, 85 patients suffered from unilateral deafness with a hearing loss of at least 80 dB in the speech frequency range. Under conservative therapy in 58 patients, there was an improvement in hearing in 19 cases and a return to normal in 6 patients. In 27 patients, the clinical history was suggestive of a possible tympanic membrane rupture, which was confirmed by tympanoscopy in 5 cases. On 5 other occasions, the intraoperative findings were highly suggestive of tympanic membrane rupture. In each case, a membranoplasty was performed. The results of operative therapy tended to give better results than conservative therapy. The presence of concomitant vestibular disorders did not influence the results of treatment in either group. The results of the study show, that apart from tympanoscopy, there are no other diagnostic criteria to recognize a membrane rupture. Typical case histories demonstrate that tympanoscopy can be useful diagnostic and therapeutic measure in cases of therapy-resistant deafness. PMID- 1755907 TI - [Dysphagia as initial symptom in tetanus. A case report]. AB - A 69-year-old woman was examined because of progressive dysphagie. A barium esophagogram showed no obstruction but a swallowing in trachea suggested a neuromuscular disorder. ENT examination showed no specific signs of infection. The clinical diagnosis of tetanus was confirmed by electromyography. This case demonstrates an uncommon cause of dysphagia where the classical signs of tetanus in the early stages of this disease were absent and dysphagia was the initial and sole presenting symptom. PMID- 1755908 TI - [Otoplasty using the CO2 laser]. PMID- 1755909 TI - [Endoscopically-controlled endonasal orbital decompression in malignant exophthalmos]. AB - In 6 patients with endocrine ophthalmopathy, indications, surgical technique and results of the endoscopic controlled endonasal orbital decompression are described in comparison to the common surgical procedures. When medical and radiation therapy fail, indications for decompression are a) loss of visual acuity or visual field defects, b) increasing strabismus, c) severe keratopathy due to eyelid retraction. The endoscopic-controlled endonasal surgical decompression technique is proceeded in three steps. First, an endonasal ethmoidectomy with resection of the middle turbinate is performed and the medial wall of the maxillary sinus is widely opened. Second, the medial and inferior wall of the orbital walls are removed, preserving the infraorbital nerve. In the last step, the periorbital area is incised and the orbital fat herniates. The advantages of this procedure consist in the absence of exterior scars and the known morbidity of a Caldwell-Luc antrotomy. The results were documented by computed tomographic scans (CT), magnetic resonance imaging (MRI), Hertel measurements, evaluation of ocular motility and ophthalmoscopy. An average of 3-4 mm improvement in Hertel-measurements could be reached. All patients had a postoperative improvement of visual acuity. 2 patients developed more significant diplopia postoperatively, whereas in all other patients ocular motility either improved or rested unaffected. Therefore, the endoscopic controlled endonasal procedure allows to obtain comparable results to the common extranasal and transantral procedures without the disadvantages of the latter. PMID- 1755910 TI - [Preservation of hearing and facial nerve function in surgery for acoustic neuroma]. AB - The results concerning the preservation of hearing and facial nerve function in 71 patients with 74 acoustic neuromas operated on from 1979 to 1990 are presented. All patients have been operated on in half-sitting position by one surgeon using the suboccipital-transmeatal approach. Postoperative facial nerve function was good (House degree I or degrees II) in 42/73 patients (58%), moderate (House degrees III or degrees IV) in 13/37 (18%), and poor (House degrees V or degrees VI) in 18/73 (24%). Preservation of useful hearing was achieved in 17%. The smaller the tumour and the easier the preparation the better was the functional result. Beside anatomic integrity of nerves and endolymphatic system the internal auditory artery as the most important vessel for the inner ear blood supply should be respected. The cochlear nerve intact in 47 patients we only found one case with recurrent tumour in a patient with neurofibromatosis 2. Preservation of the cochlear nerve did not have an increased risk of tumour recurrence in our group of patients. PMID- 1755911 TI - [Pulsatile tinnitus. Causes, diagnostic procedures, case presentation]. AB - The pulsatile tinnitus is a rare sign. It is characterised by a rhythmic sound that is synchronous with the patient's heart beat. The underlying causes vary widely and may be life-threatening. Pulsatile tinnitus may be due to cardiac or vascular malformation, metabolic disorders, hyperdynamic circulatory states, elevated intracranial pressure, and tumours. The diagnostic evaluation includes physical examination, audiologic assessment and often computed image processing for precise topodiagnosis. A case report illustrates our current management of patients with pulsatile tinnitus. PMID- 1755912 TI - [Sensitization against storage mites in allergic rhinopathy]. AB - In the past 15 years, storage mites became more common as an agent in allergic airway disease. Sensitization to storage mites has been reported in farmers and grain workers. There were some studies investigating local populations, especially in the north of Europe. The sensitization to storage mites in a rural population seems to be similar to the rate found for Dermatophagoides. The main diseases caused by storage mites are allergic rhinitis and asthma. Although there is a cross-reactivity between Dermatophagoides pteronyssinus and storage mites, most of the antigens were distinct from house dust mite antigens. In our study, we analysed sera obtained from patients with known house dust mite allergy. Patients with a RAST class 2, 3 or 4 for Dermatophagoides pteronyssinus were tested for specific IgE-antibodies against storage mites. The test was performed using the Melja EAST-technique. We obtained a sensibilization rate of 7% for Acarus siro (d70), 17% for Lepidoglyphus destructor (d71), 3% for Tyrophagus putrescentiae (d72) and 13% for Glycyphagus domesticus (d73). According to our results we can conclude that storage mites are relevant allergens in allergic rhinitis, especially in the rural population in Bavaria. Therefore, routine testing in patients with perennial rhinitis is proposed. PMID- 1755913 TI - [Laryngeal cancer in men and occupation. A comparison with male patients with stomach cancer]. AB - A statistical comparison of the professions of 1119 male patients with malignant laryngeal tumours and the profession of 708 male patients with malignant tumours of stomach, shows the influence of occupational exposures. The quantity of malignant laryngeal tumours is high in the group of steelworks- and foundry workers, workers in the glass-, porcelain-, quartz- and chemical industry and motorists. The inhalation of exogenous cancer-poisons are the probable cause. PMID- 1755914 TI - [Current diagnosis and therapy of cysts of the mouth floor]. AB - Cystic tumors of the floor of the mouth are relatively rare. Until today the exact localisation of the cysts in relationship to the muscles of the floor of the mouth is established mainly during operation. Therefore the preoperative decision for the optimal surgical approach can be difficult, at least in large space occupying lesions. In the present study the case of a 24-year-old female patient with an extensive dermoid cyst of the floor of the mouth is demonstrated. The preoperative use of magnetic resonance imaging enabled us to determine the exact localisation of the cyst in relationship to the muscular structures of the floor of the mouth. The differential diagnosis of dermoids of the floor of the mouth as well as the adequate therapeutic approach is discussed according to the relevant literature. PMID- 1755916 TI - [The removal of the bony covering in osteoplastic surgery of the frontal sinus]. PMID- 1755915 TI - [Clinical aspects of acute epiglottitis in adults]. AB - During the last three years, 79 adults suffering from acute epiglottitis have been treated in the ENT departments of the university hospital Rudolf Virchow, Berlin, 36 women (41 years of age as an average) and 43 men (average age 39 years). Acute epiglottitis developed either all of a sudden, within hours, or gradually, within days. All patients complained of dysphagia and pain in the throat; dyspnea could be observed in 20%. During examination, we could see an inflamed, thickened epiglottis with edema of the arytenoid cartilages. 55 patients reported an infection of the upper airway prior to the onset of symptoms of acute epiglottitis, epiglottic abscess developed in 11 adults. The inflammation responded satisfactorily to conservative antibiotic management (broad spectrum penicillin). Only one patient had to undergo intubation, none of the adults required tracheotomy. PMID- 1755917 TI - Physiological characterization and identification of Listeria species. AB - A total of 136 strains of the genus Listeria were physiologically characterized using 329 miniaturized tests. Overall similarities of all strains were determined by numerical taxonomic techniques using the UPGMA algorithm and the SSM and SJ coefficients. A total of 10 clusters (2 or more strains) and 1 single-member cluster were defined at the 95.1 to 95.8% similarity levels (SSM). The same clusters were found at the 76.8% to 77.8% similarity levels (SJ). Strains of L. seeligeri, L. welshimeri, L. ivanovii, L. murrayi and L. grayi were found in separate clusters and formed homogeneous taxospecies. In contrast, strains of L. monocytogenes and L. innocua formed five heterogeneous clusters and one single member cluster. For differentiation of the phena the following tests are useful: utilization of D-xylose, D-xylitol, D-ribose, D-galactose, alpha-methyl-D mannoside, methyl-alpha-D-glucopyranoside, inulin and L-rhamnose, acid production from D-glucuronate, alpha-D-galacturonate, alpha-methyl-D-mannoside, methyl-alpha D-glucopyranoside, D-xylose, L-lyxose, D-sucrose, alpha-D-melizitose, D-tagatose, and D-ribose and hydrolysis of pNP-alpha-D-glucopyranoside, pNP-alpha-D mannopyranoside and 2-deoxythymidine-5'-pNP-phosphate. Independent of the assignment of some strains of L. monocytogenes and L. innocua to the same cluster, members of these species can be separated by hydrolysis of D-alanine-p nitroanilide. PMID- 1755918 TI - Minimal requirements for growth of Brucella suis and other Brucella species. AB - Minimal nutritional requirements and temperature limits of growth were studied in Brucella suis and, comparatively, in a few other Brucella species. In a saline basic medium including thiosulphate, ammonium sulphate and glucose with addition of 2 or 4 vitamins (nicotinic acid, thiamin and panthotenic acid, biotin), 24 out of 25 B. suis, 4/6 B. melitensis and 1/6 B. abortus strains were able to grow. Some strains, however, needed to be initially induced to grow by other ingredients, CO2, other vitamins, or amino acids, or by a prolonged incubation. In the saline basic medium without ammonium, glutamic acid and/or alanine and arginine, with or without glucose, supported the growth of all the B. suis and B. melitensis strains, except 2 which required a sulphur amino acid. Five out of 6 B. abortus strains did not grow in either medium without addition of one or several aromatic amino acids or, for one strain, aspartic acid, or valine. One strain could also be induced to grow in ammonium medium by other amino acids. In a rich medium with yeast extract, all Brucella species grew at 18 degrees C and 42.5 degrees (except one) while most B. suis (14/17) grew also at 15 degrees C and 44 degrees C, in contrast to other brucellae of which a few strains only grew at these temperatures. In saline ammonium glucose medium, yeast extract at 0.1 g/l provided all the required vitamins and amino acids for all brucellae and at 1 g/l, it even provided enough nitrogen to support growth without ammonium. Such basic saline medium with yeast extract may be advantageously used in routine Brucella culture, instead of the classic undefined peptone mediums. B. suis biovar 1 strains did not differ significantly in their minimal nutritional requirements, precluding the use of these requirements to differentiate the strains, in particular the Chinese vaccine strain S2 from the reference strain 1330 or from other strains from different parts of the world. Finally, B. suis which is endowed with a nearly complete synthetic potential may represent the parental Brucella species from which the melitensis and abortus species may have evolved. PMID- 1755919 TI - Capillary gas chromatography of cellular carbohydrates as a means for the differentiation of fastidious, slow-growing or anaerobic gram-negative bacteria- a review. AB - The phenotypic differentiation of microaerophilic or anaerobic Gram-negative bacteria of human origin is traditionally based on the analysis of metabolic characteristics. Due to outstanding growth requirements of many kinds of parasitic bacteria, e.g. of the facultatively and strictly anaerobic members of the human periodontal flora, conventional biochemical tests are time-consuming and sometimes lead to doubtful results. Commercial diagnostic test kits often produce misidentifications because of insufficient databases or inappropriate test combinations. In this situation, cytochemical methods can provide an alternative. Especially in the case of Gram-negative bacteria which contain considerable amounts of carbohydrates in their cell wall lipopolysaccharide layers, capillary gas chromatography of peracetylated carbohydrate derivatives prepared from bacterial whole cell hydrolysates proved to be useful to characterize individual species, and sometimes even subspecies. As soon as a pure culture is available, the derivatization of the cellular carbohydrates to their peracetylated aldononitriles and peracetylated O-methyloximes, respectively, needs only about four hours and the gas chromatographic spectra are easy to evaluate. PMID- 1755920 TI - A polyclonal-monoclonal antibody based sensitive sandwich enzyme linked immunosorbent assay for specific detection of cholera toxin. AB - A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for specific detection of prototype cholera toxin (CT) elaborated by Vibrio cholerae serovar O1 has been developed. The use of a high affinity monoclonal antibody (MAb) for capturing of CT epitopes permitted a high efficiency. Using this ELISA, we sought in vitro production of CT from clinical strains of V. cholerae O1, Non-O1 and from LT-producing E. coli. All culture supernatants of V. cholerae O1 were positive for CT whereas V. cholerae non-O1 and LT producing E. coli were found negative for CT. This ELISA will be particularly useful in specifically designed studies where detection of CT and not of related labile toxins is mandatory. PMID- 1755921 TI - Bacteriocin typing and biotyping of clinical isolates of Serratia marcescens. AB - A total of 727 clinical isolates of Serratia marcescens from 474 patients were typed for bacteriocin susceptibility; 707 of the isolates (97.25%) were typable and comprised 46 different bacteriocin types. The biotyping method of Grimont and Grimont permitted categorization of 726 of the 727 isolates into 50 biotype profiles. However, 98 of the 726 biotypable isolates (13.5%) yielded previously unknown biotype profiles; similarly, 24 out of 59 reference strains of S. marcescens gave biotype profiles that had not been encountered before. Multiple S. marcescens isolates (366 of the 727 isolates) had been recovered from 113 patients. Phenotypic variation in bacteriocin susceptibility occurred in 15 of these patients, whereas phenotypic variation in biotype profiles was noted in 26 of these patients. In 5 of the 113 patients, phenotypic variation accounted for changes both in bacteriocin type and in biotype profile. It is suggested that serotyping should remain the method of choice until new methods have been evaluated accordingly. PMID- 1755922 TI - Serotyping of clinical isolates of Acinetobacter baumannii and genospecies 3: detection of additional serovars. AB - Continued serological monitoring of clinical isolates of Acinetobacter baumannii and genospecies 3 permitted identification of 7 new serovars of A. baumannii and 8 additional serovars of genospecies 3. PMID- 1755923 TI - Mode of action of the antimycotic agent G2 isolated from alfalfa roots. AB - The mode of action of the antimycotic alfalfa root saponin, medicagenic acid 3-O beta-D-glucopyranoside (compound G2), which possesses a pronounced antifungal activity against medically important yeasts and dermatophytes, was studied in Saccharomyces cerevisiae. Compound G2 caused lethal leakage of ions out of the yeast cells. Exposure of S. cerevisiae to compound G2 resulted in a disappearance of the main sterol, ergosterol, from the cell membranes, suggesting that compound G2 was highly specific for ergosterol. Independently, chemical data indicated that compound G2 forms stable complexes with both ergosterol and cholesterol. Addition of cholesterol or ergosterol protected the cells of S. cerevisiae and several pathogenic yeasts from the inhibitory activity of compound G2 by producing a higher ratio of sterols (mainly ergosterol) to phospholipids in the membranes. The fact that an amphotericin B-resistant Candida tropicalis was susceptible to G2 suggested that its mode of action was different from that described for polyene antibiotics. This was also confirmed by the finding that 0.2 M KCl did not protect S. cerevisiae cells against ion leakage with G2, but did so with amphotericin B. PMID- 1755924 TI - Induction of human cord blood lymphocyte proliferation by type III group B streptococci. AB - In a preceding communication, the authors have described the selective adherence of group B streptococci (S. agalactiae) to human neonatal lymphocytes. In the present one, it has been shown that cord blood lymphocytes obtained from healthy newborns possess the ability to develop proliferative responses in the presence of type III group B streptococci. When investigating the influence of these bacteria on both adult and neonatal mononuclear cells (MNC), the following patterns of adherence and lymphocyte reactivity could be observed: (1) Type III group B streptococci adhered spontaneously to lymphocytes (11.4 +/- 5.7%, n = 14) of healthy newborns but not to those from adults, (2) The capacity to proliferate was restricted to cord blood lymphocytes giving a mean peak response at day five of culture in the presence of the bacteria (6.8 +/- 2.8 times over the background, n = 15), (3) The correlation between streptococcal adherence and cord blood lymphocyte proliferation was statistically significant for 10 independent experiments (r = 0.75, p = 5%), and (4) Type III group B streptococci inhibited the Pokeweed mitogen (PWM)-induced lymphocyte proliferation in adult but not in neonatal MNC cultures. The different pattern of reactivity between adult and cord blood MNC towards group B streptococci will be discussed. PMID- 1755925 TI - Susceptibility of wild mice to Yersinia pseudotuberculosis and Yersinia enterocolitica. AB - Laboratory-born progeny and adult populations of old world woods mice (Apodemus speciosus) trapped in a certain area where Yersinia pseudotuberculosis was prevalent among wild animals, were challenged with Y. pseudotuberculosis and Yersinia enterocolitica to determine the ecology of Yersinia in wild mice. The laboratory-born progeny population was associated with infection with Y. pseudotuberculosis but not with Y. enterocolitica serotype O:3 and was found to be nearly 200 times more susceptible to infection with Y. pseudotuberculosis than were the adult populations. A. speciosus convalescing from infection with Y. pseudotuberculosis showed protection upon subsequent challenge with homogeneous and heterogeneous serotypes of Y. pseudotuberculosis. These data suggest that the prevalence of Y. pseudotuberculosis in wild mice may begin with the infection in the newborn and thus spread to the Y. pseudotuberculosis naive adult mice populations. PMID- 1755926 TI - Occurrence of bifidobacteria in the stool of multiple sclerosis patients. AB - Stool specimens from 17 multiple sclerosis (MS) patients were examined for bifidobacteria. The count of colony forming units (CFU)/g faeces and the differentiation and typing of species, especially of Bifidobacterium adolescentis biotypes were performed. The pH of the samples was also measured. Stool specimens from 17 healthy volunteers were examined as a control by the same methods (a modified medium, suitable for the detection and recognition of bifidobacteria in adults is given). The results demonstrate a significant deficiency in bifidobacteria of the adolescentis group in MS patients. In 3 patients, no bifidobacteria could be detected (less than 10(7]. In comparison with the samples from healthy donors, B. adolescentis "c" was reduced and B. adolescentis "a" could not be detected at all in MS patients' stool specimens. The occurrence of B. adolescentis "b" and B. adolescentis "d" as well as the species B. bifidum and B. longum did not significantly differ within both groups. The pH was only slightly increased in the MS group. PMID- 1755927 TI - Clinical and epidemiological aspects of Listeriosis in Belgium, 1985-1990. AB - Between January 1985 and December 1990, 233 cases of human listeriosis were reported to the Listeria Reference Centre of Belgium. Foeto-maternal infections (88 cases) and septicemia in adults (88 cases) were the most frequent clinical manifestations, followed by CNS infections (40 cases). 71.7% of the patients presented a concurrent condition which favoured the triggering of the disease. No correlation was found between the isolation of L. monocytogenes in patients and their occupation or their animal environment. The predominant serovar was 4b (70%). On the other hand, the Reference Centre also examined 1412 foodstuffs for the presence of L. monocytogenes: 16.9% (9/53) of cooked chicken products, 15.4% (73/473) of soft cheeses and 6.9% (62/886) of cooked meat products were positive (presence of L. monocytogenes in 25 g). The contamination level of these ready-to eat foodstuffs ranged from less than 10 cfu L. monocytogenes/g. to 10(6) cfu/g. 54.1% of the isolated strains belonged to serovar 1/2a. PMID- 1755929 TI - 1990 ACNP Past-President's Lecture. Where do we go from here. PMID- 1755928 TI - Use of pulsed field electrophoresis of DNA restriction fragments for comparing Listeria monocytogenes strains isolated from human infections and food in Austria. AB - Twenty-five Listeria monocytogenes strains of human and food origin were studied, using low-frequency-cleavage restriction endonucleases and pulsed field gel electrophoresis. Sixteen different restriction patterns were obtained using ApaI and SmaI. The human isolates showed profiles different from those of the food isolates, thus strongly suggesting that the two human infections selected for this study did not originate from the contaminated foodstuffs examined at the same time. This method allowed it to clearly distinguish between strains apparently similar [i.e. belonging to the same serovar and same origin (cheese samples from the same dairy plant)]. PMID- 1755930 TI - Evidence for ultrastructural changes in cortical axodendritic synapses following long-term treatment with haloperidol or clozapine. AB - A quantitative electron microscope analysis was performed to determine the effects of 1-year administration of either haloperidol or clozapine on the ultrastructure of synapses in layer VI of rat medial prefrontal cortex. The average caliber of dendritic shafts was significantly decreased in the haloperidol-treated group, but not in clozapine-treated animals; however, there was no difference between the means of the two drug-treated groups. Both drug treated groups showed a significant decrease in the relative distribution of axodendritic synapses displaying asymmetric postsynaptic membrane specializations, while there was an increase in synapses with either a symmetric membrane specialization or no specialization at all. Axospinous synapses of the clozapine-treated group showed a shift in the relative distribution of synaptic subtypes paralleling that found for axodendritic synapses. There was no change in the number of axon terminals forming a synapse on dendritic cross-sectional profiles in the neuroleptic-treated groups. Similarly, no change in the average size of axon terminals or synaptic vesicle density was detected. These data suggest that both typical and atypical neuroleptics, when administered over an extended period of time, may induce relative shifts in the distribution of excitatory and inhibitory elements synapsing on dendritic shafts and, to a lesser degree, spines. Such alterations in synaptic relationships may provide insight into the interaction of neuroleptics with intrinsic components in layer VI of medial prefrontal cortex. PMID- 1755931 TI - Concentration-related effects of morphine on cognition and motor control in human subjects. AB - Morphine and other opioid analgesics may interfere with normal cognition and motor function when the drugs are used for long-term treatment of pain. We used individually tailored steady-state drug infusions to identify the nature and extent of cognitive and motor effects of the mu-receptor-selective opioid morphine in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, constant plasma concentrations of morphine in each subject. Compared with functional assessments obtained in a separate saline infusion day, infusions of morphine to plasma concentrations in the usual therapeutic range for analgesia caused significant impairments of some but not all elements of cognitive and motor function. The time needed to encode and process serially presented verbal information increased and the ability to maintain low consistent levels of force decreased during the morphine infusion. We also assessed verbal recall 3 hours after the morphine and saline infusions. Delayed recall of information presented during the morphine infusion was significantly impaired. Our results demonstrate that morphine can interfere with cognitive and motor performance at plasma drug concentrations within the usual therapeutic range. PMID- 1755932 TI - Nonlinear analysis of EEG sleep states. AB - Recent advances in the field of nonlinear dynamics have provided new conceptual models as well as novel analytical techniques applicable to neuropsychopharmacologic studies. One measurement technique that has been recently developed in an attempt to characterize nonlinear systems in physics and biology is the estimation of dimension. Dimension may be seen as a measure of the information required to describe the current behavior of a system. We have applied these techniques to the analysis of the sleep EEG, and have found that the dimension of rapid eye movement (REM) sleep is significantly higher than non rapid-eye-movement (NREM) sleep. These data support a preliminary hypothesis that EEG dimension may represent the number of nonlinear modes activated in the brain. Thus, sleep states of low arousal or low input would be envisioned as having low dimension (e.g., slow-wave sleep) whereas increased arousal (REM) would activate more nonlinear modes. Although more investigations will be needed to explore this hypothesis, these studies suggest that further development of nonlinear approaches to the analysis of brain systems are likely to generate new clinical measures as well as new ways of viewing brain electrical function. PMID- 1755933 TI - Conversion of bromperidol to reduced bromperidol in human liver. AB - Bromperidol (BRP) is an analog of haloperidol, a potent butyrophenone neuroleptic. Reductive conversion of BRP carbonyl group to reduced bromperidol (RBRP) was confirmed in vitro using human liver. This NADPH-dependent reduction of BRP showed a similar inhibition pattern and Michaelis constants to haloperidol carbonyl reductase. PMID- 1755934 TI - Rapid eye movement (REM) sleep increases by auditory stimulation reverted with biperiden administration in normal volunteers. AB - Auditory stimulation during REM sleep increases REM sleep time. The purpose of the present work was to determine if the selective muscarinic M-1 antagonist biperiden could modify the effect of the auditory stimulation on REM sleep. Twelve healthy volunteers were divided into placebo and biperiden groups. All the volunteers were studied under sleep laboratory conditions as follows: one acclimatization night, one baseline night, four nights with auditory stimulation either with placebo or biperiden, and two follow-up nights. Biperiden (4 mg) or placebo in identical capsules was administered 1 hour before beginning the sleep recordings. REM sleep time and REM density in the placebo group were increased relative to baseline by auditory stimulation. Biperiden blocked the REM time increase over the three treatment nights and suppressed the REM density increase over all four treatment nights. Biperiden also increased the latency compared to the placebo group. The present findings suggest that M-1 mechanisms are related to REM sleep regulation. PMID- 1755935 TI - The CTLA-1 gene: a member of the granzyme multigene family in human and murine cytotoxic T cells. PMID- 1755936 TI - The growth hormone/prolactin receptor gene family. AB - The identification of cDNAs encoding receptors for growth hormone and prolactin have allowed the identification of the primary structure of these receptors. The expression of these receptors can be measured in various tissues by estimation of mRNA levels using cDNA probes and measurements of protein levels by radioimmunoassay or immunoblot analysis using monoclonal or polyclonal antibodies to the receptors. Site-directed mutagenesis of ligand-binding domains will lead to an understanding of the residues important for hormone binding. In addition, mutagenesis of the cytoplasmic domains of the receptors performed together with functional tests should help identify regions of the receptor involved in the process of signal transduction. Finally, the identification of the enlarged receptor family, including receptors for cytokines, should shed some light on additional functions of growth hormone prolactin, especially in regulating immune functions. PMID- 1755937 TI - Organization and evolution of satellite, minisatellite and microsatellite DNAs in teleost fishes. PMID- 1755938 TI - Nucleosome positioning and regulated gene expression. PMID- 1755939 TI - The biology of complement. PMID- 1755940 TI - Biology of complement: the overture. PMID- 1755941 TI - Evolution of the complement system. AB - The ancestral form of the alternative pathway of complement activation probably originated as a primitive independent immune system. Subsequent evolution of an adaptive immune response drove the specialization of the classical pathway to connect antibody-mediated nonself recognition to the complement-dependent effector mechanisms. In this article Timothy Farries and John Atkinson consider how the contemporary complexity arose by a succession of credible alterations at the genetic level, and the selective advantages provided at each step. PMID- 1755942 TI - C1: molecular interactions with activating systems. AB - The molecular events controlling complement activation have been gradually unravelled over the past three decades, stimulated by improved isolation procedures and a better understanding of the roles of individual proteins. In this review, Bob Sim and Ken Reid examine the interactions between C1q and its numerous ligands in the initiation of the classical pathway cascade. PMID- 1755943 TI - The role of complement in inflammation and phagocytosis. AB - Inflammation and phagocytosis are highly complex events involving many humoral and cellular factors, with complement components playing a key role. As described here by Mike Frank and Louis Fries, complement peptides trigger cell function, aid in the recognition of invading pathogens and regulate the phagocytic process via interactions with specific cell surface receptors. PMID- 1755944 TI - The role of C3 in the immune response. AB - The complement system, particularly the third component, plays an important modulatory role in the inductive phase of the immune response. As discussed here by Anna Erdei and colleagues, the picture that is emerging is that immobilized C3 split products facilitate the cooperation between immunocompetent cells and are co-stimulatory molecules in T- and B-cell activation, probably as a result of their ability to promote cell-cell adhesion. In contrast, soluble C3 products inhibit lymphocyte proliferation. PMID- 1755945 TI - The response of human platelets to activated components of the complement system. AB - Many in vivo platelet responses are considered to be mediated, directly or indirectly, by activated components of the complement system. These include the secretion of proteolytic enzymes and the assembly of key enzymes of the coagulation and fibrinolytic pathways. In this review, Peter J. Sims and Therese Wiedmer summarize the known interactions of human platelets with the complement system and discuss the implications of these interactions for platelet hemostatic function within the vasculature. PMID- 1755946 TI - [Granuloma in Crohn's disease of the colon and rectum--a study of resection specimens]. AB - The aim of the present study was to investigate frequency and distribution of granulomas in resected specimens of patients with well known Crohn's disease. Granulomas were observed in 57% (8/14) of all cases. Their distribution varied remarkably between different sections of the same resectional sample as well as between the patients. 11.6% of all granulomas were found within the lamina propria, 42.9% within the submucosa, and 45.5% within the muscularis propria. The mean value per cm muscularis mucosae was 0.85 +/- 0.82 granulomas. Caused by the heterogeneity in frequency and distribution there is no guarantee for a successful identification of this helpful parameter. During the last years the diagnosis Crohn's disease became more and more certain even in absence of granulomas. Therefore they are an useful but dispensable feature. PMID- 1755947 TI - Bilirubin or plasminogen--which is better in the assessment of the severity of viral hepatitis? AB - The purpose of the present paper was to asses the values of plasminogen (PLg) as severity index in viral hepatitis (VH). The results were compared with serum bilirubin (SB) and prothrombin time. The following groups of patients were investigated: I- VH (n-672); II- Fulminant hepatitis (FH)(n-53); III-Liver cirrhosis (n-52); IV- Cholangiohepatitis (21); Toxic hepatitis (n-22); V- Gall stone (n-56) VI- Neoplasms with jaundice (n-56); VII- Healthy subjects (n-137). PLg was found to be diminished in parenchymal liver diseases, especially in VH's patients according to the severity and the stage of the diseases. The most impressive decline was observed in FH--more than 50% of the tests showed Plg activity less than 10% (reverence values 83-126% activity). In VH, PLg was superior to SB and prothrombin time when evaluating the severity of the disease at the time of admission in the hospital. We proposed PLg as valuable criterion for the severity of VH. The range being as follows: Light forms of VH- PLg activity above 70%; Medium forms-from 69 to 50%; Severe forms-from 49 to 20% and patients with high risk of liver coma-PLg activity below 20%. PMID- 1755948 TI - [The effect of various non-ulcer pharmaceuticals on nocturnal gastric pH in healthy subjects]. AB - The effects of 4 non-ulcer drugs and the M1-antagonist pirenzepine on the nocturnal intragastric pH were investigated in 12 healthy volunteers. We tested single doses of pirenzepine (100 mg), Chlorprothixene (30 mg), clonidine (75 micrograms), ketotifen (3 mg) and nifedipine (30 mg) in an randomized, single blind, cross-over study. The nocturnal intraluminal pH is significantly elevated not only by pirenzepine but also by the other substances. As expected pirenzepine (mean nocturnal pH = 2.49 +/- 0.22) shows the most distinct effect, nifedipine (mean nocturnal pH = 1.72 +/- 0.20) the most sparsely effect. The other drugs are nearly half as effective as pirenzepine. The acid suppressive side effect of the non-ulcer remedies is considered to be important for the treatment of ulcer patients with concomitant diseases. PMID- 1755949 TI - [Ultrasonography studies on spontaneous and pharmacologically modified gallbladder motility]. AB - The intra- and interindividual variations of gallbladder motility were sonographically studied in 10 healthy subjects. We investigated the following criteria: a) the gallbladder volumes after overnight fasting on 5 consecutive days, b) the spontaneous motility under fasting over 12 or 24h at hourly intervals, c) the emptying rate and time of maximal contraction after stimulation with sorbitol, and d) the emptying rate and time (like c) after premedication with "cholagogic" drugs (Cholecysmon, Divalol), nifedipine, indomethacin or N butylscopolaminiumbromide. We found a great intrapersonal and interpersonal variability in gallbladder volumes after overnight fasting in consecutive days. In subjects fasting over 24h phases of dilatation with maxima at 12 AM and 4 PM alternated with phases of contraction with maxima at 8 AM and 4 PM. After premedication with nifedipine, indomethacin and N-butylscopolaminiumbromide a significant decrease of the emptying rate was observed. The time of maximal contraction did not differ however. After premedication we found a distinct intra and interindividual variability too. Cautious interpretation of gallbladder motility studies is necessary. PMID- 1755950 TI - [Microsomal phospholipid pattern and liver ultrastructure of aging rats following treatment with essential phospholipids]. AB - The treatment of aging rats with 100 or 300 mg/kg "essential" phospholipids (EPL) for 10 weeks significantly changed the microsomal concentration of phosphatidyl serine plus phosphatidyl inositol. The most marked alterations of the phospholipid fatty acid pattern predominantly observed with unsaturated fatty acids were detectable even 7 days after cessation of EPL application. Ultrastructurally, an enrichment in the hepatocytes with rough endoplasmic reticulum was visible which was more prominent in acinus zone 3. The changes after EPL administration are regarded as the expression of an increased membrane fluidity. PMID- 1755951 TI - [Gastric and duodenal polyps in acromegaly]. AB - Relationship between acromegaly and occurrence of colonic cancer and polyps is well-known. A rare case of gastric and duodenal polyps in a patient with hypophyseal adenoma is described. After selective hypophysectomy a regression of the polyps was observed. Probable mechanisms of the development and the regression of polyposis are explained. The diagnostic value of gastroscopy in the screening for polyps in patients with acromegaly is discussed. PMID- 1755952 TI - [Is provocation ultrasonography diagnostically helpful in divided pancreas?]. PMID- 1755953 TI - A practical approach to dose reduction for imaging staff. PMID- 1755954 TI - Setting up a clinical educators' course. PMID- 1755955 TI - Myelography--an assessment of communication with a view to improving patient care and standardising information. PMID- 1755956 TI - Treatment information and the radiotherapy patient. PMID- 1755957 TI - Radiological appearances of a dorsal fracture dislocation of the lunate. PMID- 1755958 TI - Nonexpression of the human serum amyloid A three (SAA3) gene. AB - Serum amyloid A (SAA) is a major acute-phase plasma protein synthesized by the liver. In addition to the two major plasma isoforms described in humans (SAA1 and SAA2), a third form (SAA3) has been demonstrated in several other species and is distinguished by predominant extrahepatic expression. Two clones, Ch11g5-1-1 and HDg1-1, containing the human SAA3 gene are described in this report. The human SAA3 gene is comparable in organization to the SAA1 and SAA2 genes and shares with them 87% nucleotide identity in the region spanning exon 3 through exon 4. Sequences 5' to exon 3, however, are strikingly different from those in the SAA1 and SAA2 genes. For instance, the sequence deduced for amino acids 1-12 (exon 2) has only 25% identity with human SAA1 and SAA2; it most closely resembles that of rabbit SAA3 isolated from synovial fibroblast cultures (75% identity). Although rabbit SAA3 induces collagenase production in an autocrine fashion the human SAA3 gene is not expressed. This is shown by: (i) a single base insertion in the sequence corresponding to codon 31, (ii) the inability of a 918-bp fragment immediately upstream from SAA3 exon sequences to direct transcription of a chloramphenicol acetyltransferase reporter gene, and (iii) the absence of detectable human SAA3 in mRNA. PMID- 1755959 TI - Similarity between the amino-terminal portion of mammalian 58-kD sterol carrier protein (SCPx) and Escherichia coli acetyl-CoA acyltransferase: evidence for a gene fusion in SCPx. AB - A computer analysis of the amino acid sequences of rat and human 58-kD sterol carrier protein and Escherichia coli acetyl-CoA acyltransferase reveals that the two proteins have a segment of about 350 residues with strong sequence similarity. The ALIGN comparison scores for the rat and human sterol carrier proteins and the E. coli enzyme are 8.25 and 8.8 SD, respectively. The catalytically active cysteine of E. coli acetyl-CoA acyltransferase (cysteine 91) aligns with cysteine 93 and cysteine 94 on human and rat 58-kD sterol carrier protein, respectively. PMID- 1755960 TI - [Female career makers]. PMID- 1755961 TI - [Wound care. Introduction]. PMID- 1755962 TI - [Wounds and wound healing]. PMID- 1755963 TI - [Wound care--those that cannot take it simply disappear]. PMID- 1755964 TI - [AIDS center--hospitals--nursing homes]. PMID- 1755965 TI - [Wound care products]. PMID- 1755966 TI - [Nursing perspective of wound care. Nursing process and wound care plan in district nursing]. PMID- 1755967 TI - [The WCS classification for local wound care (Woundcare Consultant Society)]. PMID- 1755968 TI - [Various facts from the history of wound care]. PMID- 1755969 TI - [Wound care in extramural health care]. PMID- 1755971 TI - T-cell tolerance to viruses. AB - T-cell tolerance to self antigens is maintained by events that occur within the thymus and in the periphery. Mechanisms that operate on immature T cells within the thymus are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to break down. This failure of peripheral mechanisms to induce T-cell tolerance to viruses has implications for autoimmunity and for treatment of chronic viral infections. PMID- 1755970 TI - T-cell receptor and T-cell-resistant virus variants. AB - Analysis of the T-cell receptor has revealed the molecular basis of antigen recognition by T cells specific for viral antigens. Studies using T-cell receptor transgenic mice have provided evidence for clonal deletion of virus-specific T cells in persistently infected hosts and for selection of T-cell-resistant virus variants in vivo. PMID- 1755972 TI - Cytokines in viral diseases. AB - As in many other areas of cytokine biology, recent studies of the role of cytokines in viral disease reveal numerous complex interactions that in many instances may contribute directly to the development of pathology. For example, data from the rapidly evolving field of human retrovirology has shown that these viruses, as well as inducing the expression of many cellular cytokine genes, can be activated from latency and driven into replication/expression by the very same cytokines. The continuing rapid expansion of knowledge in the cytokine area augers well for eventual development of novel antiviral therapeutic strategies based on manipulation of the cytokine network. PMID- 1755973 TI - Targeting and controlled release of antigens for the effective induction of secretory antibody responses. AB - Increased awareness of the fact that the mucosal membranes are the portals of entry for the majority of infectious agents, and that antibodies in external secretions often correlate better with protection than do corresponding antibodies in serum, has prompted many recent studies aimed at the selective induction of antibodies in mucosal secretions. The recent development of novel technologies (expression of antigens in various microbial vectors that colonize mucosal surfaces and incorporation of antigens in biodegradable microspheres) indicate that the goal of vaccination with enhanced induction of both mucosal and systemic immune responses is attainable. PMID- 1755974 TI - The implications for malaria vaccine programs if memory T cells from non-exposed humans can respond to malaria antigens. AB - Although the goal of current candidate vaccines is to expand a population of malaria antigen-specific lymphocytes, accumulating evidence suggests that peripheral blood of adult humans contains significant numbers of malaria-specific T cells prior to any exposure to vaccine or actual infection. The reason why such naive humans are susceptible to malaria infection may thus relate not to inadequate T-cell surveillance but to some other factor--possibly lack of suitable splenic modification. It is possible that current vaccine programs are misdirected because these other factors are not being addressed. The possibility of an attenuated vaccine should be re-examined. PMID- 1755975 TI - Antibody affinity and protection in virus infections. AB - Affinity of viral antibodies matures slowly after primary virus infections. Recent investigations with human sera and mouse monoclonal antibodies have provided the first evidence for a role of antibody affinity in the pathogenesis of chronic virus infections. More detailed studies are necessary before the rules and exceptions of this phenomenon are revealed. PMID- 1755976 TI - Mimicry in Trypanosoma cruzi: fantasy and reality. AB - Chronic infection of mammals by Trypanosoma cruzi often results in severe autoimmune and inflammatory pathology. Extensive antigen cross-reactivity between the parasite and its mammalian hosts has also been reported. These findings have stimulated speculation that Trypanosoma cruzi uses antigenic mimicry as a mechanism for escaping the host immune system. This may not be the case and the observed antigen cross-reactivity may be a result of perturbations of the immune system such that common, normally tolerated antigens are recognized in infected animals. The parasite, however, does appear to use functional mimicry to survive in the immune competent host. PMID- 1755977 TI - Genetics of the immune response to infectious pathogens. AB - In this selective review of the recent literature in the field of genetically determined host resistance to infection, we highlight five areas in which research is directed towards the search for proteins encoded by genes that function to maintain a 'resistant' phenotype in the face of challenge by a variety of pathogenic organisms. In particular, we discuss newly described genes that may regulate host resistance, newly described functions of genes previously identified, the reverse genetics approach to cloning an elusive gene, a direct genetics approach to a similar problem, and the role of the major histocompatibility complex in regulating our ability to resist challenge by infectious organisms. PMID- 1755978 TI - New viruses and new disease: mutation, evolution and ecology. AB - Given the extraordinarily high mutation rate of viruses, particularly those with RNA genomes, it is not surprising that new viruses are continually evolving. However, the symptomatology of old viral diseases has remained stable for centuries. The combination of genetic and ecological factors that constrain as well as facilitate the emergence of new viruses is analyzed. PMID- 1755979 TI - Control of human immunodeficiency virus replication by the tat, rev, nef and protease genes. AB - Immediately after infection, human immunodeficiency virus directs the synthesis of three regulatory proteins tat, rev and nef that together allow the synthesis of the structural proteins of the virus after a delay of several hours. Viral mRNA production is controlled by the tat gene, which appears to stimulate elongation by RNA polymerase II, and the rev gene, which allows the accumulation of unspliced or partially spliced mRNAs in the cytoplasm. The nef gene is dispensible for virus growth but may limit virus spread by downregulating the levels of cellular surface proteins such as the CD4 receptor. Virus maturation also depends critically on the protease gene which allows the orderly rearrangement of the viral core structures in newly budded virions as well as the vpu and vif genes which allow efficient production of mature envelope glycoprotein. PMID- 1755980 TI - HIV types and testing. AB - The past year has seen the discovery of new isolates which do not readily fit into the established categories HIV-1, HIV-2 and SIV, as well as the availability of new assays including the use of the polymerase chain reaction. New combination enzyme-linked immunosorbent assays can detect viruses from two or more groups where specific enzyme-linked immunosorbent assays have been developed using peptides and monoclonal antibodies. PMID- 1755982 TI - Immunity to infection. PMID- 1755981 TI - Severe combined immunodeficiency disease, adenosine deaminase deficiency and gene therapy. AB - Patients with severe combined immunodeficiency disease represent a model for the first clinical applications of gene therapy. Present attempts use insertion of the human adenosine deaminase gene into the peripheral blood T lymphocytes of patients who lack this gene. The ultimate treatment, however, will require insertion of the normal human adenosine deaminase gene into pluripotent stem cells and expression of the gene in their progeny. PMID- 1755983 TI - Immunodeficiency. PMID- 1755984 TI - Protein tumor antigens. AB - Immunogenic tumor antigens have been sought through a variety of paradigms for several past decades. Recent developments in antigen presentation have radically changed the prism through which we view these enigmatic antigens. This article discusses the small but growing treasure chest of these antigens--stress-induced proteins, the P1AB antigen of the P815 mastocytoma, the p53 tumor suppressor protein, the gp95/p97 antigen of human melanoma, mucins and others. PMID- 1755985 TI - Cellular and humoral immune responses against cancer: implications for cancer vaccines. AB - The key issue in tumor immunology is to identify antigens as target structures for a cancer-selective immunological attack in the tumor-bearing host, resulting in tumor rejection. There is a growing detailed understanding of structural and regulatory gene alterations giving rise to candidate rejection antigens and peptides in tumor cells. As well as reviewing the development of new adjuvant and recombinant vector systems, new approaches are suggested for the construction of cancer vaccines. PMID- 1755986 TI - Imaging and therapy with monoclonal antibodies in non-hematopoietic tumors. AB - Although radiolabelled monoclonal antibodies are useful in tumor imaging, in our opinion their most important role is in the evaluation of the capacity of newly developed monoclonal antibodies to localize in tumors specifically. Intravenous injections of monoclonal antibody fragments, labelled with beta-emitting radionuclides, can completely eradicate large human colon carcinoma xenografts in nude mice whereas this is not achieved by unconjugated monoclonal antibodies. New strategies are being developed to make radioimmunotherapy applicable to carcinoma patients. PMID- 1755987 TI - Cytokines and cancer: experimental systems. AB - The transfer of certain cytokine genes into cancer cells can provide very powerful suppression of tumor growth in the absence of any toxic side effects. Some of these cytokines, such as interleukin-4, granulocyte colony-stimulating factor and tumor necrosis factor, can mediate powerful immune suppression even in T-cell-deficient animals and appear to be effective for poorly or non-antigenic tumors. However, approaches must be found to induce or deliver cytokines locally at the tumor site. PMID- 1755988 TI - Transplantation tolerance. AB - New experimental protocols for the induction of transplantation tolerance continue to be developed. In the past year, encouraging data have been reported from a clinical trial using a protocol specifically designed to induce tolerance to the histocompatibility antigens of the kidney donor. Progress has also been made in our understanding of the mechanisms responsible for the induction and maintenance of tolerance to alloantigens in vivo; it is becoming increasingly clear that more than one mechanism can be involved, particularly at different phases in the response. PMID- 1755989 TI - Structural aspects of allorecognition. AB - The phenomenon of T-cell allorecognition of foreign major histocompatibility molecules has been one of the more enigmatic aspects of T-cell immunology. The molecular basis for allorecognition is unfolding as a result of the application of major histocompatibility complex structure/function analyses in the light of current insights into the three-dimensional structure of major histocompatibility complex products. PMID- 1755990 TI - Discordant xenografting: challenges and controversies. AB - The transplantation of organs between individuals of disparate species is being considered as a potential solution to a serious shortage of donor organs for clinical transplantation. We summarize recent papers concerning the immunologic barrier to xenotransplantation, the pathogenesis of hyperacute rejection and reports on efforts made to prevent or mitigate hyperacute xenograft rejection. PMID- 1755991 TI - Use of monoclonal antibodies in human transplantation. AB - Monoclonal antibodies are of growing importance in human organ transplantation in the prophylatic and curative treatment of cellular rejection. Among the pan T lymphocyte monoclonal antibodies, OKT3 has been much studied, although clinical research is engaged with more selective targets of allorecognition and/or their consequences, for example monoclonal antibodies directed against the interleukin 2 receptor, adhesion molecules and CD4 molecules. We summarize the use of these monoclonal antibodies and bioreagents in clinical transplantation. PMID- 1755992 TI - Recent developments in the human maternal-fetal immune interaction. PMID- 1755993 TI - Rodent maternal-fetal immune interactions. PMID- 1755995 TI - Cancer. PMID- 1755994 TI - Lymphohematopoietic cytokines in the female reproductive tract. AB - The past year has seen an avalanche in publications describing the synthesis of lymphohematopoietic cytokines by the uterus and placenta. Dissection of the particular contributions of these factors will require genetic as well as biochemical approaches. The major events of the year therefore, were the identification and creation of mouse mutants that have provided novel insights into the roles of various cells and cytokines during gestation. PMID- 1755996 TI - Transplantation. PMID- 1755997 TI - Reproduction. PMID- 1755998 TI - The potential role of biosensors in the food and drink industries. AB - Despite their apparent potential as analytical tools in the food and drink industries, only a few biosensors are used routinely. This article describes the development of biosensors for these sectors and discusses the technical and economic problems of applying this technology to the monitoring of food and drink products. PMID- 1755999 TI - The development of a catechol enzyme electrode and its possible use for the diagnosis and monitoring of neural crest tumours. AB - A catechol enzyme electrode is described, in which a Clark-type oxygen electrode is coupled to immobilised polyphenol oxidase in albumin cross linked with glutaraldehyde on a dialysis membrane. Electrode calibration, response time, pH response profile, stability, detection limit and selectivity are evaluated and the feasibility of using the electrode for the measurement of catecholamines in the urine of patients with neural crest tumours is assessed. PMID- 1756000 TI - Electrochemical detection of viable bacteria in urine and antibiotic selection. AB - An electrode system consisting of a basal-plane pyrolytic graphite (BPG) electrode and a porous nitrocellulose membrane filter to trap bacteria was used for the detection of bacteria in urine. The peak current of a cyclic voltammogram increased with increasing initial cell concentration of Escherichia coli in urine. Urine containing from 5 x 10(2) to 5 x 10(5) cells ml-1 was measured with this system. The susceptibility of bacteria to various antibiotics was also determined from the peak current. The minimum inhibitory concentration values obtained by the electrochemical method were in good agreement with those obtained by the conventional method. PMID- 1756001 TI - An FIA biosensor system for the determination of phosphate. AB - A flow injection analysis (FIA) biosensor system for the determination of phosphate was constructed using immobilized nucleoside phosphorylase and xanthine oxidase and an amperometric electrode (platinum vs silver/silver chloride, polarized at 0.7 V). When a phosphate-containing sample was injected into the detection cell, phosphate reacted with inosine in the carrier buffer to produce hypoxanthine and ribose-1-phosphate in the presence of nucleoside phosphorylase. Hypoxanthine was then oxidized by xanthine oxidase to uric acid and hydrogen peroxide, which were both detected by the amperometric electrode. The response of the FIA biosensor system was linear up to 100 microM phosphate, with a minimum detectable concentration of 1.25 microM phosphate. Each assay could be performed in 5-6 min and the system could be used for about 160 repeated analyses. This system was applicable for the determination of phosphate in various food products and plasma, and the results obtained agreed well with those of the enzymatic assay. PMID- 1756002 TI - An evanescent fluorescence biosensor using ion-exchanged buried waveguides and the enhancement of peak fluorescence. AB - The principle of an optical molecular sensor using ion-exchanged buried planar waveguides in glass has been demonstrated. We have shown both theoretically and experimentally that the intensity of the peak evanescent fluorescence can be increased by several orders of magnitude with the use of an index-matching material. The method of differential measurement has been used to improve the differentiation between specific and non-specific binding. We used h-IgG (human immunoglobulin G) as the immobilized antibody on the surface of the waveguide and protein A-FITC (fluorescein isothiocyanate) as the fluorescently labelled antigen or anti-antibody to be detected, and have shown that a concentration of protein A as low as 24 nM can easily be detected. PMID- 1756003 TI - Potentiometric enzyme channeling immunosensor for proteins. AB - A potentiometric immunosensor for the detection of human IgG has been developed using an asymmetric, ion-selective membrane with immobilized adenosine deaminase and IgG. A protein A-alkaline phosphatase conjugate binds to the immobilized IgG, creating a bienzymatic catalytic layer. In the presence of sample IgG, the conjugate does not bind to the membrane. Instead, the intermediate in the two step reaction (adenosine) must diffuse to the membrane surface, reducing the rate of product (ammonium) formation within the diffusion layer detected by the membrane. The immunosensor demonstrated is for the determination of IgG. A simplified model is described to predict the maximum rate enhancement for the 'channeled' versus 'unchanneled' reaction mechanisms. PMID- 1756004 TI - [Microbiologic validation in the production of sterile pharmaceuticals]. AB - Some microbiological validation procedures for sterile drug production are described. There concern the environmental microbial and particle "self decontamination" time specified in the English "Guide to Good Pharmaceutical Manufacturing Practice 1983" and the EEC "Guide to Good Manufacturing Practice for Medical Products", the various methods for evaluating that sealing of sterile drugs is intact and the validation methods for aseptic filling of sterile powders and solutions. For these, the limits laid down in FDA regulations are indicated. PMID- 1756005 TI - Diethylhexylphthalate (DEHP) and triethylhexyltrimellitate (TEHT) PVC plasticizers assay in blood. AB - The interest in the PVC biocompatibility of the apparatus used both for dialysis and any other extracorporeal blood circulation is so real that a method to determine PVC plasticizer concentration in blood is properly needed. The described method might be easier than other ones we are allowed to use at the moment. PMID- 1756006 TI - [A centralized system of particle counting in controlled zones]. AB - The air quality is the primary concern of the environmental control program in aseptic operations of pharmaceutical industry. The article reports on the development of the air particulate monitoring in the sterile manufacturing areas. In this respect, it presents a new approach which provides more assurance of acceptable air quality in the immediate environment of the manufacturing process and puts the emphasis on the preventive aspect. This approach is now possible by using available advanced systems which permit a continuous and simultaneous airborne particulate monitoring of critical manufacturing areas. PMID- 1756007 TI - Evaluation of the interfacial properties of a new potent antimicrobial surfactant C31G. AB - The surface activity of a new potent antimicrobial mixture (C31G) of alkyl betaines and alkyl amine oxides were evaluated in order to determine the relationship between its antimicrobial effectiveness and physical properties. Therefore the surface tension measurements were performed at different temperatures using an interfacial tensiometer. Critical micelle concentrations, interfacial and thermodynamic parameters of C31G were obtained from the surface tension data. PMID- 1756008 TI - [Metabolic destination and toxicologic profile of hydroxypropyl beta cyclodextrin]. PMID- 1756009 TI - [Anaerobic co-digestion of RSU and macro-algae in the Venice lagoon. Preliminary results]. AB - In these last few years in the lagoon of Venice the phenomenon of eutrophization has increased. The possibility of turning to an anaerobic digestion of the biomass seems to be interesting. In this view, the following experiment describes a study on the co-digestion of mechanically selected algaebiomass and organic fraction of solid urban waste. The results relevant to both yield parameters and process stability are reported, which have been obtained by monitoring a 3 m3 pilot digestor during a running period of about 85 days, under different working conditions. PMID- 1756010 TI - [Wet oxidation of toxic industrial waste with oxygenated water]. AB - The industrial toxic waste streams hot treatment technology with hydrogen peroxide and catalysts, developed by the research laboratories of Montefluos in Bollate, allows the abatement of many organic and bio-toxic pollutants. Some treatment examples are here reported. The examples, performed on a laboratory scale, relate to industrial waste streams with a high COD (100000-200000 mg/l) in which it was possible to obtain an abatement over the 90% of pollutants like phenols, formaldehyde, dimethylformamide and phenyl acetate. The application range of this technology is similar to that of oxygen or air wet oxidation, but it has remarkable advantages due to the lower plant, maintenance and energy costs, because the treatment is performed using much more bland conditions (atmospheric pressure and 90-100 degrees C of temperature). The aim of the bio toxic pollutants abatement and COD reduction (70-80%) is to allow the final bio digestion waste streams with high organic content, but too diluted to be directly incenerated at a suitable cost. PMID- 1756011 TI - Green wastes from Barcelona city. Influence of process parameters on the anaerobic digestion plant. AB - A sensibility analysis of the assumed operating conditions is carried out to test its influence on the performance of an anaerobic digestion plant to treat the organic fraction of the wastes of a large food market. The results shows that the filter press is an important equipment in the plant. PMID- 1756012 TI - Relationship between serum concentrations of flecainide and fluoride in humans. AB - The biotransformation of flecainide to serum fluoride after the oral administration of 100 mg to six healthy subjects was studied. Fluoride, flecainide acetate, calcium and alkaline phosphatase serum levels were determined at 0, 3, 4.5 and 6 hours after administration. Higher mean serum concentrations for fluoride and alkaline phosphatase (P less than 0.01, P less than 0.005) and lower mean calcium levels (P less than 0.05) were reached at 4.5 hours. The flecainide acetate serum levels ranged from 108 to 261 ng/ml. The results were analyzed for statistical significance by single factor analysis of variance with repeated measures. The Spearman rank correlation coefficient between flecainide acetate and fluoride serum increases was calculated. Our results would suggest that fluorine-containing flecainide could be biotransformed to yield some ionic fluoride which contribute to the daily fluoride intake. PMID- 1756013 TI - [The "challenge test" in the European pharmacopoeia]. PMID- 1756014 TI - [Control of rabies with a vaccine produced from recombinant DNA]. PMID- 1756015 TI - Hereditary breast cancer. PMID- 1756016 TI - Suicides in the young: an increasing medical problem. PMID- 1756017 TI - HLA antigens in insulin-dependent diabetes mellitus. AB - Diabetes mellitus is largely determined by genetic factors but environmental factors are necessary to convert genetic susceptibility into overt disease. Studies of twins show that the genetic impact in non-insulin-dependent diabetes mellitus is stronger than in insulin-dependent diabetes mellitus. The genetic factors involved in non-insulin-dependent diabetes mellitus are not known and the outcome of molecular genetic research has so far been disappointing. The major genetic susceptibility to insulin-dependent diabetes mellitus is conferred by genes in the HLA region on chromosome 6. Despite many advances in molecular genetics in insulin-dependent diabetes mellitus the serologically detectable HLA antigens and haplotypes are still the best available markers. This review describes the important developments in immunogenetics in insulin-dependent diabetes mellitus and summarises the main findings from earlier studies. Genetically the potential for primary prevention of insulin-dependent diabetes mellitus already exists and will become a reality as soon as the environmental determinants are identified. A wide application of immunogenetic methods will be needed in the prevention of insulin-dependent diabetes mellitus. PMID- 1756018 TI - Corticotropin-releasing hormone and opioid peptides in reproduction and stress. AB - Increased knowledge on the mechanisms whereby corticotropin releasing hormone (CRH) and opioid peptides mediate the effects of stress has helped us to understand the relationship between stress and disturbed reproductive function. Increases of CRH and beta-endorphin in the hypothalamus in stressful situations inhibits the secretion of gonadotropins, oxytocin and vasopressin. This may lead to amenorrhea, which often is a consequence of intensive training or psychological stress, or it may disrupt parturition and lactation. There is a relationship between ovarian function and opioid peptides in the hypothalamus. Opioid peptides increase during puberty and fall at the menopause. Oestradiol and progesterone increase beta-endorphin concentrations in the luteal phase of the menstrual cycle, and this is followed by a rapid fall at menstruation. These changes may mediate symptoms typical of the premenstrual syndrome. Rather intensive exercise is required to increase plasma concentrations of beta endorphin and corticotropin. During labour the amounts of beta-endorphin and corticotropin reach the values found in athletes during maximal exercise. The placenta produces increasing amounts of CRH towards the end of pregnancy which may help the mother and fetus to withstand the increased demands of labour. The placenta may thus be involved in the adaptation of the stress mechanism during pregnancy. CRH has also a paracrine function in different biological processes of the placenta and fetal membranes. It is possible to counteract the deleterious effects of stress on reproductive function by the administration of opiate antagonists. Induction of ovulation with naltrexone has been shown in patients with hypothalamic amenorrhea but the effect on fertility is not known. PMID- 1756019 TI - Ultraviolet radiation in skin ageing and carcinogenesis: the role of retinoids for treatment and prevention. AB - The mechanisms of UV-induced ageing and carcinogenesis of the skin have been elucidated in animals and humans, and both UVB and UVA radiation have been shown to have deleterious effects on the skin. Thus the use of solaria which deliver mostly UVA radiation is not safe. There is also an increased risk of ageing when using therapeutic UV sources. UV radiation is beneficial in many cases of skin disorders such as psoriasis, atopic eczema, acne and pruritus. Nevertheless by careful patient selection and follow-up the risks of UV can be minimised when treating patients with artificial UV radiation. During recent years there has been intensive research into the development of agents which prevent harmful effects of radiation. The retinoids are particularly interesting as they enhance skin repair after UV damage, have an anticarcinogenic effect and are effective for treating precancerous lesions such as solar keratosis and as adjuvant therapy for skin cancers. Topical retinoids are already used for the treatment of actinic skin damage, and systemic retinoids are also used in certain groups of patients who have an increased risk of contracting skin cancers such as xeroderma pigmentosum. PMID- 1756020 TI - Current status of small bowel transplantation. PMID- 1756021 TI - Cardiopulmonary exercise testing has limited value in diagnosing heart failure. AB - Usefulness of cardiopulmonary exercise testing in the diagnosis of heart failure was evaluated in a study of 59 patients with clinically suspected heart failure (22 men and 37 women) and 75 healthy control persons (34 men and 41 women), aged 45-74 years. Patients were classified according to certainty of the diagnosis by the Boston criteria: 27 patients were "unlikely" to have heart failure (group I), 19 had "possible" (group II) and 13 had "definite" heart failure (group III). Oxygen consumption at peak exercise and at the appearance of the ventilatory threshold was lower in group III than in the control group (15.6 +/- 1.5 versus 26.0 +/- 0.8 ml/min/kg, p less than 0.001 and 11.8 +/- 1.5 versus 18.0 +/- 0.4 ml/min/kg, p less than 0.001, respectively). However, the distribution of oxygen consumption values was wide in both the control and patient groups, and considerable overlapping of values between study groups was observed. Thus, cardiopulmonary exercise testing appeared to be of limited value in the diagnosis of heart failure. PMID- 1756022 TI - Acute phase reaction, infarct size and in-hospital morbidity in myocardial infarction patients treated with streptokinase or recombinant tissue type plasminogen activator. AB - We examined the acute phase reaction in myocardial infarction after thrombolytic treatment by streptokinase or tissue plasminogen activator. The magnitude of the acute phase reaction as determined by measurements of serum C-reactive protein and amyloid-A protein did not correlate with infarct size (determined by serial measurements of creatine kinase-MB) in this patient population. On the other hand, the development of acute cardiac failure was more closely associated with the magnitude of the acute phase reaction than with infarct size. The peak serum values of C-reactive protein in patients with and without acute cardiac failure were 128 mg/l (95% confidence intervals 85-170) and 60 mg/l (30-89); P less than 0.01 and concentration time integrals 578 mg/l x days (368-787) and 205 mg/l x days (62-350); P less than 0.01. The corresponding creatine kinase-MB values were 310 U/l (191-429) and 207 U/l (125-289) not significant; and 319 U/l x days (201 437) and 204 U/l x days (124-286) not significant; respectively. Patients requiring medication for cardiac failure on discharge from hospital had higher C reactive protein and serum amyloid A protein values than those who did not, although the difference did not quite reach statistical significance. The infarct sizes were similar whether the patients needed medication for cardiac failure at discharge or not. Subjectively felt morbidity due to myocardial infarction was linearly associated with serum C-reactive protein peak values (P less than 0.05) and concentration time integrals (P less than 0.05), but not with infarct size. We conclude that thrombolytic treatment of myocardial infarction may reduce hospital inpatient morbidity independently of the limitation of infarct size. This diminished morbidity seems to be associated with modest or low acute phase reaction. PMID- 1756023 TI - Infection as a risk factor for infarction and atherosclerosis. AB - A growing amount of clinical and experimental evidence suggests a link between infection and atherosclerotic diseases including both myocardial and cerebral infarction. A prime example is a greatly increased risk of stroke in septicaemic patients with and without endocarditis. Controlled clinical studies have recently shown, however, that certain other milder bacterial infections are also a risk factor for infarction. A preceding febrile respiratory infection was a major risk factor for stroke in young and middle aged patients. In patients with acute myocardial infarction Chlamydia pneumoniae and dental infections seem to be risk factors according to one controlled clinical study. Several possible mechanisms could explain the observed association of infection and infarction. For instance, infection causes a hypercoagulable state which increases the risk of thrombosis. In addition, infection has profound and harmful effects on prostaglandin and lipid metabolism. Infection may also have some role in the atherosclerotic process itself by inducing damage and inflammation in vascular endothelium in the presence of hypercholesterolemia. So far, however, little clinical evidence is available to suggest that by controlling infection the risk of infarction or development of atherosclerotic lesions might be reduced except in patients with endocarditis, where the risk of thromboembolic complications rapidly diminished when the infection is controlled with antimicrobial therapy. PMID- 1756024 TI - Platelets, endothelium-dependent responses and atherosclerosis. AB - Basal release of endothelium-derived relaxing factor (EDRF) and prostacyclin from intact vascular endothelium may inhibit continuously platelet aggregation. If local platelet aggregation occurs, platelet-derived adenine nucleotides stimulate the release of EDRF. Stimulated EDRF release may override the direct vasoconstrictor effects of other platelet products such as thromboxane and serotonin resulting in local vasodilatation. In addition, stimulation of EDRF release by adenine nucleotides may inhibit further platelet adhesion and aggregation by a feedback mechanism. Thus, intact vascular endothelium may play an important role in the defense against platelet deposition and vasospasm. In atherosclerosis, basal and stimulated release of EDRF is markedly reduced. Endothelial dysfunction will impair this protective mechanism and will favour vasoconstriction and further platelet disposition. Occurrence of occlusive thrombus formation in patients with coronary artery disease may be pathophysiologically related to this impairment of endothelial defense. PMID- 1756025 TI - Mast cell granule-mediated uptake of low density lipoproteins by macrophages: a novel carrier mechanism leading to the formation of foam cells. AB - Mast cells are present in the arterial intima, the site of atherogenesis. To gain insight into the possible role of mast cells in the formation of the cholesterol loaded macrophage foam cells typical of both early and late atherosclerotic lesions, a model system was developed in which isolated rat serosal mast cells were incubated with mouse peritoneal macrophages in medium to which low-density lipoproteins (LDL) had been added. Stimulation of the mast cells was found to induce a 50-fold enhancement of LDL uptake by the macrophages, which concomitantly accumulated LDL-derived cholesterol. This process, called the "granule-mediated uptake of LDL", involves the following steps: (i) exocytosis of the cytoplasmic granules of the mast cells, (ii) escape of soluble granule components, such as histamine and a fraction of the granule heparin proteoglycans into the medium, leaving granule remnants consisting of neutral proteases embedded in a heparin proteoglycan matrix, (ii) binding of LDL to binding sites on the glycosaminoglycan side chains of the heparin proteoglycan component of the granule remnants, (iv) proteolytic degradation of the bound LDL by the neutral proteases of the granule remnants, (v) fusion of degraded LDL particles on the surfaces of the granule remnants, and (vi) phagocytosis of the LDL-laden granule remnants by the macrophages. Simultaneously, the soluble heparin proteoglycans, to which no proteolytic enzymes are bound, interact with LDL with formation of insoluble complexes which are also phagocytosed by the macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756026 TI - Recent evidence for the involvement of catecholamines and of macrophages in atherosclerotic processes. AB - The atherogenetic uptake of low density lipoprotein (LDL) is accelerated by the catecholamines adrenaline and noradrenaline at their pathophysical blood concentrations in rabbits and rats. A similar effect in man could account for the coronary risk factor status of cigarette smoking, hypertension, stress, etc. when associated with elevated circulating catecholamines. In human atheromatous lesions, the concentration of macrophages is greater in plaques which have fissured or ulcerated than in those which have not. This is compatible with the proposition that macrophages contribute to plaque fissure, the commonest immediate cause of coronary thrombosis. PMID- 1756027 TI - Effect of antioxidants on oxidative modification of LDL. AB - Human low density lipoprotein (LDL) with a molecular mass of 2.5 million contains on average 1300 molecules of polyunsaturated fatty acids (PUFAs) bound in the different lipid classes. The predominant antioxidant in LDL is alpha-tocopherol, with an average of 6 molecules in each LDL particle. The other substances with potential antioxidant activity are: gamma-tocopherol, beta-carotene, alpha carotene, lycopene, cryptoxanthin, cantaxanthin, phytofluene and ubiquinol-10. Each is present in amounts of only 1/20th to 1/300th of that of alpha-tocopherol. If LDL is exposed to oxidative conditions (Cu++ ions, macrophages) a lag phase precedes the oxidation of PUFAs. During the lag phase the antioxidants disappear with alpha-tocopherol the first to go and beta-carotene the last. The lag phase, which can readily be determined, is an index of the oxidation resistance of LDL. If LDL is loaded with vitamin E in vitro its oxidation resistance increases linearly with its alpha-tocopherol content according to the equation, y = kx+a. The same relationship is applicable if the alpha-tocopherol content of LDL is increased by taking oral vitamin E. Daily doses of 150, 225, 800 and 1200 IU RRR alpha-tocopherol increased the LDL alpha-tocopherol on average to 138%, 158%, 144% and 215% of the initial value, the oxidation resistance being increased to 118%, 156%, 135% and 175%, respectively. The efficiency of vitamin E-dependent (= k) and the vitamin independent (= a) oxidation resistance seem to be subject specific with strong individual variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756028 TI - Mitochondria, oxygen and reperfusion damage. AB - Reperfusion of the ischaemic or hypoxic heart elicits a number of oxygen dependent processes such as cell lysis and Ca2+ uptake. It is known that the energisation of mitochondria, which requires oxygen, plays a key role in these processes and that the organelle actively sequesters Ca2+ under these circumstances. In this brief review we discuss how oxidants derived from mitochondrial electron transport may perturb mitochondrial calcium handling on reoxygenation of the hypoxic myocardium. In addition we show that the immunosuppressive agent cyclosporin has little or no effect on the oxygen dependent increase in total cell Ca2+ which occurs when hypoxic myocytes are reoxygenated. This result suggests that the Ca2+ dependent mitochondrial pore, which is known to function under conditions of oxidative stress, does not play a major role in the perturbation of Ca2+ homeostasis which occurs on reoxygenation of hypoxic hearts. PMID- 1756029 TI - Calcium--a neglected key factor in arteriosclerosis. The pathogenic role of arterial calcium overload and its prevention by calcium antagonists. AB - Using specific calcium antagonists as experimental tools, both the physiological messenger and current carrying function of calcium ions as well as their pathogenetic potencies could be elucidated. Notably, excess intracellular calcium signalling and intra- and extracellular calcium overload turned out to be pathogenetic principles of general importance. In this context, progressive calcium overload of arteriosclerotic vascular walls and the antiarteriosclerotic effects of calcium antagonists, deserve particular interest. In fact, with the help of calcium antagonists, arterial calcium overload as decisive component of various types of experimental arteriosclerosis became accessible to a direct therapeutic intervention. According to their responsiveness to calcium antagonists, two pathophysiologically different types of experimental coronary plaques could be characterized: (1) The calcium type, i.e. coronary calcinosis of vitamin D3-intoxicated rats highly sensitive to calcium antagonist treatment, (2) the cholesterol type, represented by coronary atheromata of cholesterol intoxicated rabbits; this primary coronary cholesterol accumulation could not be inhibited by calcium antagonists. The formation of conventional human coronary artery plaques is characterized from the very early lesion onwards by a progressive local uptake of calcium, finally leading to lethal consequences. Conversely, the analysis of the mural cholesterol does not allow to discriminate arteriosclerotic from normal coronary artery segments. Thereby, conventional human coronary plaques typically represent a calcium-dominated type of human arteriosclerosis and differ widely from plaques produced in cholesterol-fed rabbits. The results indicate the decisive pathophysiological role of calcium and calcium overload in both calcium-dominated types of experimental arteriosclerosis and conventional human coronary artery plaques. Moreover, the antiarteriosclerotic effects of calcium antagonists are demonstrated to be based- in various types of experimental arteriosclerosis--on the inhibition of intra- and extracellular calcium overload of arterial walls evoked by various risk factors (vitamin D3 intoxication, hypertension, nicotine, diabetes). PMID- 1756030 TI - Use of adaptive behavior measures and overrepresentation of black students in programs for students with mild mental retardation. AB - The use of adaptive behavior information for classification and placement of black and white students with mild mental retardation was compared and overrepresentation of black students in special classes was analyzed. Adaptive behavior measures were not used to the same extent as general intelligence tests for either group, despite court decisions and recommendations by authoritative sources. Direct comparisons on general intellectual functioning and several indices of adaptive behavior yielded few differences, suggesting that an equal treatment conception of fairness was achieved despite substantial overrepresentation of black students in programs for students with mild mental retardation. Use of adaptive behavior needs to improve significantly to comply with legal requirements. PMID- 1756031 TI - Side effects during lithium treatment for psychiatric disorders in adults with mental retardation. AB - Previous clinical trials using lithium with individuals who have mental retardation have not emphasized the incidence of side effects. During a 58 consecutive-week period at an outpatient clinic for adults with psychiatric illness and mental retardation or borderline intellectual functioning, 67% (10 out of 15) patients had side effects. The percentage is similar to reports of side effects during lithium treatment in the general population. Results suggest that adults with mental retardation who take lithium may be as prone to side effects as those in the general population. PMID- 1756032 TI - Rett syndrome: a comprehensive review of the literature. AB - A comprehensive review of Rett syndrome, a recently identified developmental disability found only in females, was presented. The syndrome involves severe physical and mental handicaps. The rapidly accumulating research on Rett syndrome was reviewed for readers without a medical background. A brief history of Rett syndrome, the diagnostic criteria for this disorder, and the clinical stages that have been noted were presented. Information on the incidence of Rett syndrome and a discussion of issues in differential diagnosis (particularly with autism) was also included. The etiological data and genetic theories were then discussed as were treatment approaches and prognosis. PMID- 1756033 TI - Assessing the acceptability of behavioral treatments to persons with mental retardation. AB - Individuals with mild to moderate mental retardation living in community residential settings (Experiment 1) or an institutional setting (Experiment 2) rated the acceptability of differential reinforcement and time-out applied to a mild and a severe behavior problem. Using analogue methodology similar to previous treatment acceptability studies (e.g., Miltenberger, Lennox, & Erfanian, 1989; Tarnowski, Rasnake, Mulicke, & Kelly, 1989), and a simplified rating scale developed for persons with mental retardation, community-based subjects rated differential reinforcement as more acceptable than time-out for the mild problem, whereas institutionalized subjects rated time-out as more acceptable than differential reinforcement when applied to the severe problem. These results were discussed and future research suggested. PMID- 1756034 TI - Emergence and maintenance of stereotypy and self-injury. AB - A three-level model was used to explain the emergence and maintenance of rhythmic stereotypy and self-injury. Level I represents rhythmic behaviors as internally regulated and common in normally developing infants, but delayed in onset among children with handicapping conditions. Consistent with homeostasis theory, Level II considers stereotypy and self-injury as adaptive responses to under- or overstimulating environments. Level III represents stereotypy and self-injury as learned behaviors emitted to control the behavior of others. The model includes fluid transitions between the levels. Implications for assessment intervention and prevention were discussed and further research suggested. PMID- 1756035 TI - EPA-requested workshop identifies research priorities for bioremediation technologies. PMID- 1756036 TI - New data base supports innovative technologies. PMID- 1756037 TI - Electrokinetic remediation applications studied at Sandia National Labs. PMID- 1756038 TI - Making cleanup decisions at hazardous waste sites: the clean sites approach. AB - This paper provides a summary of the results of an 18-month study conducted by Clean Sites, Inc. of Alexandria, Virginia. The study was designed to take a critical look at the way remedies are selected for abandoned hazardous waste sites that are cleaned up under the authority of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund) and to develop recommendations for improving that process. The recommendations were released in an October 1990 report entitled "Improving Remedy Selection: An Explicit and Interactive Process for the Superfund Program." Through a cooperative agreement with the U.S. Environmental Protection Agency, Clean Sites is working to test these recommendations. At two actual Superfund sites, Clean Sites will assist EPA in performing the remedy selection in accordance with the process Clean Sites has developed. PMID- 1756039 TI - An analysis of biomedical waste incineration. AB - The California Air Resources Board (ARB) completed a series of source tests of eight operating biomedical waste incinerators (BMWI) under conditions of typical operation. The emissions of certain metals, and chlorinated dioxins and furans in the flue gases of BMWI are relatively high in comparison to emissions from other combustion sources, such as hazardous waste or municipal waste incinerators of modern design. This study reports on an analysis of the status of the existing regulatory framework and the California data base. Clarification of definitional issues at the federal level is needed to effectively treat BMWI management issues. Although few relationships among combustion parameters and emissions were uncovered, patterns of emissions were evident, suggesting commonality and relationships among the waste stream constituents and emissions. Potential implications for future research, operation of BMWI, controls and source reduction and waste segregation strategies are also discussed. PMID- 1756040 TI - Annual average radon concentrations in California residences. AB - A study was conducted to determine the annual average radon concentrations in California residences, to determine the approximate fraction of the California population regularly exposed to radon concentrations of 4 pCi/l or greater, and to the extent possible, to identify regions of differing risk for high radon concentrations within the state. Annual average indoor radon concentrations were measured with passive (alpha track) samplers sent by mail and deployed by home occupants, who also completed questionnaires on building and occupant characteristics. For the 310 residences surveyed, concentrations ranged from 0.10 to 16 pCi/l, with a geometric mean of whole-house (bedroom and living room) average concentrations of 0.85 pCi/l and a geometric standard deviation of 1.91. A total of 88,000 California residences (0.8 percent) were estimated to have radon concentrations exceeding 4 pCi/l. When the state was divided into six zones based on geology, significant differences in geometric mean radon concentrations were found between several of the zones. Zones with high geometric means were the Sierra Nevada mountains, the valleys east of the Sierra Nevada, the central valley (especially the southern portion), and Ventura and Santa Barbara Counties. Zones with low geometric means included most coastal counties and the portion of the state from Los Angeles and San Bernardino Counties south. PMID- 1756041 TI - A comparison of in situ vitrification and rotary kiln incineration for soils treatment. AB - In the hazardous waste community, the term "thermal destruction" is a catchall phrase that broadly refers to high temperature destruction of hazardous contaminants. Included in the thermal destruction category are treatment technologies such as rotary kiln incineration, fluidized bed incineration, infrared thermal treatment, wet air oxidation, pyrolytic incineration, and vitrification. Among them, conventional rotary kiln incineration, a disposal method for many years, is the most well established, and often serves as a barometer to gauge the relative success of similar technologies. Public sentiment on environmental issues and increasingly stringent environmental regulations has, over time, spurred design and development of innovative thermal treatment processes directed toward reducing harmful emissions and residuals that may require further treatment or disposal. In situ vitrification (ISV), a technology that combines heat and immobilization, is one such innovative and relatively new technology. This paper presents a comparison of ISV and rotary kiln incineration for soils treatment in the areas of process performance, process residuals, process limitations, applicable or relevant and appropriate (ARARs) regulations, criteria and limitations, and costs. PMID- 1756042 TI - Preoperative risk analysis in patients receiving Jarvik-7 artificial heart as a bridge to transplantation. AB - To distinguish high-risk patients prior to implantation of a Jarvik-7 artificial heart as a bridge to transplantation, our 37 attempts were reviewed retrospectively. Arbitrary scores of 1 to 4 were given for nine preoperative factors on the basis of results obtained by uni- and multivariate analyses between successful cases and failed attempts; transplant rejection (scored 4: S4) or postoperative heart failure (S3) as the indication, recipient height less than 175 cm (S3), body surface area less than 1.8 m2 (S3), hyperbilirubinemia greater than 24 microM/l (S2), preoperative renal failure requiring dialysis (S2), weight less than 60 kg (S2), and age greater than 40 years (S1). All except one of the 16 patients with successful bridge had a total score of less than 4, with an average score of 1.3 in contrast to 6.6 in the 21 failed cases (p less than 0.001). Among the 17 patients who scored less than 4, 15 received transplants (specificity 90%), while only one qualified for transplantation among 20 patients who scored 4 or more (sensitivity 94%). The two unpredicted failures resulted from mediastinitis and pulmonary infarction, both attributable to postoperative management. Multiple preoperative factors in combination could have successfully predicted the outcome of mechanical support in our experience. These results underscore the importance of patient selection to achieve successful and effective use of the Jarvik-7 as a bridge to heart transplantation. PMID- 1756043 TI - Antibiotic prophylaxis in non-cardiac thoracic surgery: cefazolin versus placebo. AB - A total of 127 patients (57 given placebo and 70 given a single preoperative dose of 1 g cefazolin) undergoing thoracic surgery were included in a randomized double-blind trial. The two groups were similar in regard to mean age, sex ratio, in-hospital stay before surgery, underlying disease, risk factors, type of surgery, mean duration of surgical procedure, and mean duration of chest tube drainage. The relative risk of wound infection of the patients from the placebo group was 3.27 (range 1.5-11.5; 95% confidence interval). Cefazolin significantly reduced (p less than 0.01) the wound infection rate--1 case (1.5%) in the cefazolin group versus 8 cases (14%) in the placebo group--but not the incidence of postoperative pleural empyema--5 (7%) versus 8 cases (14%)--or nosocomial pneumonia--3 (4%) versus 5 cases (9%). Cultures were made from 3 out of 9 wound infections and Staphylococcus aureus or S. epidermidis was isolated in all 3. In addition, cultures were made from 6 out of 13 pleural cavity infections and S. aureus (1 case) or other microorganisms (5 cases) were isolated in all 6. Mortality was similar in both groups and all deaths unrelated to the infections. No adverse side effects of the drug were encountered. In conclusion, a single preoperative dose of 1 g cefazolin proved to be effective for reducing the wound infection rate in non-cardiac thoracic surgery. PMID- 1756044 TI - Assessment of the response to chemotherapy in oesophageal cancer. AB - Thirty-eight patients with localised oesophageal carcinoma have been studied by computed tomography (CT) and barium swallow before and after preoperative chemotherapy and the results correlated with the pathological findings in the resected specimen. Overall 48% of patients showed a complete or partial response to chemotherapy on CT, compared with 50% on barium and 94% on pathological examination. This study highlights deficiencies in CT scanning and barium swallow as methods of assessing the regression of tumor bulk following chemotherapy for oesophageal carcinoma. We suggest that strict and specific criteria will have to be laid down before the results of chemotherapy in this disease can be reliably and accurately evaluated. PMID- 1756045 TI - Reoperation for bioprosthetic valve dysfunction. A decade of clinical experience. AB - During the 1970s, initial clinical experience with bioprostheses determined their worldwide use. However, bioprosthetic reoperation (BPR) is now common, particularly in groups with extensive implantation of these valve substitutes. From January 1980 to December 1989, a total of 470 patients had a total of 618 reoperations for bioprosthetic dysfunction and were retrospectively analyzed. Eighty-seven patients required a second BPR, 21 a third BPR, 5 a fourth BPR and 1 patient a fifth BPR. Structural deterioration was the main cause of valve dysfunction for the first and second BPR. However, paravalvular leak and infective endocarditis were more frequent for the remaining additional reoperations. Hospital mortality was 12.6%, 14.9% and 37% after the first, second and third or subsequent BPR, respectively. Univariate statistical analysis shows as hospital mortality risk factors: age at the time of the surgery, preoperative NYHA functional class IV, emergency surgery, concomitant tricuspid surgery, double (mitro-aortic) valve dysfunction, active infective endocarditis as the cause of failure and prolonged aortic cross-clamping time. Hospital mortality declined from 19.8% to 11.8% for the first and second half decade, respectively (P less than 0.005). In conclusion, bioprosthetic valve reoperation entailed a higher hospital mortality, particularly in the risk group of patients. In our hands, surgical experience has determined the improvement of the clinical results in this group of patients. PMID- 1756046 TI - Preservation of the pulmonary annulus in total correction of tetralogy of Fallot. Decreasing transannular gradients in the early follow-up period. AB - The integrity of the pulmonary annulus was preserved in 21 of 22 children consecutively subjected to total correction of tetralogy of Fallot. There was one early death (4.8%). The 20 survivors were studied prospectively and constitute the basis of this report. Mean age was 59.3 +/- 35.3 months (range 6 months-12 years). Eight patients (40%) had previous Blalock-Taussig shunts and 3 (15%) had associated cardiac anomalies. Two-dimensional Doppler echocardiography had demonstrated right ventricle to main pulmonary artery peak systolic gradients of 75.4 +/- 12.7 mmHg (range 50-104 mmHg). Ventricular infundibulectomy was carried out in all patients but one, who had abnormal coronary anatomy. Extensive incision or resection of hypertrophied or abnormal muscle bands was performed. Pulmonary valve commissurotomy was performed in 14 patients (70%), 10 (50%) had autologous pericardium supravalvular enlargement of the pulmonary trunk and one (5%) had an infundibular bovine pericardial patch. Intraoperative, postrepair right/left ventricular pressure ratios were 0.67 +/- 0.18 (range 0.41-1.0). All ratios were accepted, because all patients were haemodynamically well and only two required inotropic (dopamine) support. There was no late mortality. During the early follow-up period (mean 13.0 +/- 5.4 months, range 7-25 months), all patients had two-dimensional Doppler echocardiography measured gradients at discharge (mean 44.2 +/- 22.6 mmHg, range 10-86 mmHg; p less than 0.001 vs. preoperative values), at 3 months (mean 31.1 +/- 14.5 mmHg, range 8-64 mmHg; p less than 0.011 vs. values at discharge) and at 6 months (mean 28.5 +/- 14.3 mmHg, range 12-57 mmHg; p = 0.009 vs. values at discharge). A similar favourable evolution of the diameters of the pulmonary annulus and of the right pulmonary artery was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756047 TI - Adenosine cardioplegia: reducing reperfusion injury of the ischaemic myocardium? AB - Hyperkalaemia-induced hypopolarization of the sarcolemnal membrane during standard crystalloid cardioplegic arrest potentiates calcium influx during reperfusion and is associated with depletion of high-energy phosphate reserves. Adenosine has been shown to induce fast cardiac arrest whilst preserving membrane hyperpolarization in an isolated rat heart model. In this study we compared the efficacy of adenosine, both as an arresting agent and as an ultrastructural, haemodynamic and high-energy phosphate preserving agent, in an in situ global ischemia model in the baboon with St. Thomas' Hospital solution No. 2 (ST2; n = 8) and with Krebs-Henseleit buffer (KHB; n = 7). The addition of 10 mM adenosine to the non-cardioplegic KHB (ADO; n = 8) improved haemodynamic recovery significantly in terms of cardiac index (91.6% +/- 7.2 vs 59.9% +/- 9.9) and stroke volume index (101.6% +/- 8.9 vs 55.6 +/- 10.0) and was not statistically distinguishable from the ST2 with regard to cardiac index (91.6% +/- 7.2 vs 94.8% +/- 5.8), stroke volume index (101.6% +/- 8.9 vs 114.0% +/- 8.3) or left ventricular dP/dt (73.1% +/- 9.9 vs 87.0% +/- 12.4). Adenosine triphosphate was best preserved with ADO (103.5% +/- 21.1 vs 67.9% +/- 9.3 and 48.5% +/- 8.7) although this was not statistically significant. This suggests therefore that the mechanism of cardioprotection by adenosine occurs by means other than its role as high-energy phosphate precursor. PMID- 1756048 TI - An experimental study of hot air thermocoagulation in cardiac surgery. AB - Recently a thermocoagulator using hot air has been developed. It has been used for haemostatic purposes in a number of cases of liver, pulmonary and retroperitoneal cancer surgery. An experimental animal study was undertaken to evaluate the use of the thermocoagulator during cardiac surgery. Since the thermocoagulator produces coagulation necrosis, the epi-/myocardium including the epicardial coronary arteries was investigated microscopically for acute and chronic histopathological changes. The investigation demonstrated that the thermocoagulator is an effective hemostatic tool during cardiac surgery. The histological examination of the hearts has shown that the technique does not damage the myocardium or the coronary arteries neither at the time of application nor in the long term. PMID- 1756049 TI - Aortic valve replacement in Cogan's syndrome. AB - Cogan's syndrome is a systemic vasculitis of autoimmunologic origin. The main disturbances involve the eye, the ear and the heart, but many other structures can also be affected. Nonspecific abnormal laboratory findings are also present. The disease usually involves a cranial nerve, followed by aortitis which can affect the aortic valve and, more rarely, the cusps of the valve. Aortic lesions strongly influence the course of the disease and therefore the prognosis. When choosing the type of valve replacement, long-term corticosteroid therapy and the age and sex of the patient must be taken into account. PMID- 1756050 TI - Coarctation of the aorta associated with calcific aortic thrombosis in a neonate. AB - We report an unusual case of association of aortic coarctation with a calcified thrombus at the site of coarctation. To the best of our knowledge this is also the first such case that has been successfully treated. PMID- 1756051 TI - Persistent pleural effusion and post-traumatic subarachnoidal-pleural fistula. AB - Post-traumatic subarachnoidal-pleural fistulae are rare. We have found 22 cases in the literature. A patient who was successfully treated by thoracotomy 1 1/2 years after blunt thoracic trauma is presented. Myelography is the diagnostic test of choice and surgical closure is necessary in most cases. PMID- 1756052 TI - Simultaneous right ventricular contraction and left ventricular fibrillation during cardiopulmonary bypass. AB - Two cases of brief left ventricular fibrillation concurrent with a beating right ventricle during cardiopulmonary bypass are described. Although no left or right ventricular dysfunction was detected postoperatively, this regional electrical heterogenicity suggests inhomogeneous myocardial protection during at least a short period of time. The precise mechanisms concerned are not clear and limited clinical and animal experimental analogies can be found in the literature. PMID- 1756053 TI - Fatal and nonfatal immersion injuries among New Jersey residents. AB - We identified immersion injuries of New Jersey residents from mortality and hospital discharge data. The incidence rate was 2.3 immersion injuries (1.3 fatal and 1.0 nonfatal) per 100,000 population per year. Incidence rates were elevated among young children, men, blacks, and residents of counties in the southern part of the state. Case fatality ratios increased with age and were higher for men than for women from 10 to 50 years of age. PMID- 1756054 TI - Postrace morbidity among runners. AB - We examined two general measures of morbidity, musculoskeletal problems and respiratory symptoms, among participants of a 42 km race. We compared the morbidity experience of these participants to runners racing shorter distance events (5 km and 10 km) on the same day. Male marathon runners were almost twice as likely (and female marathon runners four times as likely) to report a lower extremity musculoskeletal problem in the month after the race as nonmarathon runners. Although adjusting for other factors did not change the crude odds ratio for either men or women, logistic regression results indicated that the strongest factor associated with lower extremity musculoskeletal problems in the month after the marathon was the report of a musculoskeletal problem in the year before the marathon. Neither male nor female marathon runners reported an excess of respiratory symptoms compared to those who ran shorter distances. However, a report of respiratory symptoms in the month before the race was statistically associated with respiratory symptoms in the month after the race. These results suggest that runners who have had lower extremity musculoskeletal problems in the year before, or those who have recently experienced respiratory symptoms, should use caution when preparing for and recovering from racing events. PMID- 1756055 TI - Estimation of outpatient risk characteristics and influenza vaccination status: validation of a self-administered questionnaire. AB - As part of an effort to evaluate the effectiveness of a multifaceted, institution wide influenza vaccination program, we mailed a self-administered postcard questionnaire to 500 randomly selected outpatients following both the 1987-1988 and 1988-1989 immunization seasons. The postcard asked if the patients received influenza vaccine, where they were immunized, whether they had any high-risk medical illnesses, their age at their last birthday, and their name. To assess the validity of the questionnaire, following the 1988 survey, we selected a 25% systematic sample of respondents and compared survey responses with medical record documentation. Response rates for the surveys were 77.6% for the 1988 survey (two mailings) and 86.5% for the 1989 survey (three mailings). Ninety-four percent (n = 89) of charts selected for audit were successfully reviewed. Agreement between questionnaire responses and medical records was excellent, with greater than 90% agreement and kappas of .8 to .9 for classifying patients as high-risk and receipt of vaccine at the Department of Veterans' Affairs Medical Center. For other data, agreement ranged from 84% to 96% with kappas of .6 to .75. Responses to the 1989 survey also demonstrated the importance of sample frame definition and response wave on estimates of risk characteristics and vaccination rates. A self-administered postcard questionnaire is a valid tool for estimating outpatient risk characteristics and influenza vaccination rates. PMID- 1756056 TI - Development of a paraprofessional home visiting program for low-income mothers and infants. AB - This article reports the development of a paraprofessional home visiting program based upon empirically documented client needs, maintenance of the qualities of mutuality and cooperation found in the indigenous paraprofessionals, and methods of ongoing program revision. Three studies are described that suggested four areas of program emphasis: (1) continuity of services from pregnancy through infancy, (2) needs assessment procedures sensitive to a broad range of health and social problems, (3) an ongoing personal relationship with an indigenous paraprofessional, and (4) reduction of barriers to prenatal care inherent in the health care system itself. We provide examples of program application and revision through training of paraprofessionals, case management procedures, and interventions within the perinatal health care system. PMID- 1756057 TI - The making of a smoke-free hospital may not be as easy as you think. AB - Literature describing experiences in the implementation of a smoke-free policy in a hospital suggests that, with careful preparation and close monitoring, a smoke free policy can be successfully instituted. Despite this pervasive viewpoint, any hospital personnel considering the adoption of a smoke-free policy should be aware that the institution of such a policy may be quite difficult. The experience at University Hospital suggests that a strong policy statement, administrative support, and a comprehensive implementation plan have helped to achieve widespread compliance with the smoke-free policy among hospital employees. Unfortunately, the smoke-free policy has been less successful changing the smoking activities of the patients. Although others have not reported this compliance problem, we believe it is a real problem that many institutions will face. We present methods used to identify, combat, and monitor this compliance problem. PMID- 1756058 TI - Demographic, psychosocial, and medical correlates of Pap testing: a literature review. AB - The approaches used to ensure regular Pap testing must be tailored to sociodemographic, psychosocial, medical, and motivational factors that may change over a woman's life. Careful descriptions of the determinants of Pap testing at different stages are needed; the success of Pap-emphasizing programs designed without this information may be severely limited. We review the literature on demographic and psychosocial correlates of Pap testing and on the relationship of Pap smear frequency to contact with the medical care system and to preventive health behaviors. We include a discussion of factors related to preventive health behavior in general, so that the Pap test can be viewed against a range of behaviors. Pap program efforts must focus more precisely; our review of the available literature provides recommendations for improving Pap screening programs. PMID- 1756059 TI - Birthweight-specific infant mortality risk in cesarean section. AB - The role of cesarean section in improving infant survival has not been clearly documented. We calculated birthweight- and race-specific infant, neonatal, and postneonatal mortality risks by method of delivery for single- and multiple delivery infants, using data from 14 states, reported to the Centers for Disease Control through the 1980 National Infant Mortality Surveillance project. For single-delivery infants, the risk of death for infants delivered by cesarean section was 1.6 times higher than for infants delivered vaginally among blacks and 1.2 times higher among whites. The risk was 1.7 times higher during the neonatal period and 1.2 times higher during the postneonatal period. For infants with birthweight less than 1,000 grams, the risk of death was lower when infants were delivered by cesarean section. The risk of death among multiple-delivery infants born by cesarean section was significantly lower than for those born vaginally. This analysis demonstrates that, unlike other birthweight categories, infants with a very low birthweight may have better outcomes if delivered by cesarean section. However, we cannot recommend the routine use of cesarean section for delivering very low birthweight infants. Further studies are needed to determine survival of such infants after controlling for maternal and infant conditions that prompted delivery by cesarean section. PMID- 1756060 TI - Helmet use among competitive cyclists. AB - The United States Cycling Federation (USCF) decision in 1986 to mandate helmet use in all sponsored races marked a major initiative in cycling safety. Confirming earlier reports about the effectiveness of helmets in preventing injuries, this study also examines the attitudes of 554 USCF members toward the policy and about helmet use in both racing and nonracing situations. Although 64% of the racers reported some hardshell helmet use in training before the policy, 80% used helmets in training after the ruling. Most cyclists favored the USCF policy, although only 19% favored requiring helmet use in all cycling situations. Attitudes about helmet policy and actual use by racers were inconsistent; large percentages of those opposing mandatory helmet use in racing (51%) and in training (76%) used helmets themselves. We suggest possibilities for incremental expansion of helmet use requirements for all riders. PMID- 1756061 TI - Physical fitness is inversely related to heart disease risk: a factor analytic study. AB - We measured cardiorespiratory endurance, muscular strength and endurance, anaerobic run time, coronary risk factors, and dietary habits in male fire fighters (n = 779, ages 18 to 64 years) and performed factor analysis to determine the interrelationships and underlying factor structure of the data set. Principal component analysis produced nine factors (eigenvalues greater than 1.0) accounting for 61% of the total variance. However, the variable loadings were inconsistent, preventing a meaningful interpretation of the factor solution. These problems were solved through the principal axis method of common factor analysis, which revealed three factors (eigenvalues greater than 1.0) accounting for 29% of the total variance. Orthogonal rotation (varimax method), showed Factors 1, 2, and 3 accounting for 52%, 29%, and 19%, respectively, of the common variance. Factor 1, labeled physical fitness capacity (PFC), included age, situps, treadmill performance time, pushups, maximum exercise heart rate, and anaerobic run time. Factor 2, designated coronary risk status (CRS), included body mass index, resting systolic and diastolic blood pressure, triglycerides, and the total cholesterol-high density lipoprotein cholesterol ratio. Factor 3, termed food frequency intake (FFI), included the weekly intake of fried foods, beef, pork, eggs, caffeine, and cheese. Percentage body fat loaded on both PFC and CRS. Measures such as blood pressure, grip strength, resting heart rate, maximum exercise systolic blood pressure, cigarettes smoked per day, and weekly frequency of milk, fish, fowl, and alcohol intake contributed little to the factor solution. Correlation coefficients after oblique rotation showed PFC to be inversely related to CRS (r = -0.48). However, FFI was independent of PFC (r = 0.07) and CRS (r = -0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756062 TI - Cancer risk reduction counseling: a computer-assisted curriculum. AB - Significant progress has been made in the identification of factors associated with an increased risk of developing cancer. Cancer is increasingly viewed as a preventable disease. Its prevention involves risk reduction counseling. This counseling is an important skill for the family physician but can be difficult to learn and to teach. We used a prototype, computer-assisted cancer risk reduction counseling curriculum with first-year medical students. We found a statistically significant change in both knowledge-based and attitudinal questions and answers after the use of this curriculum. PMID- 1756063 TI - Preventive medicine residency training: a resident's perspective. AB - Preventive medicine as a discipline confronts considerable internal and external pressure today about society's needs for prevention specialists. Training in the field has remained static in the face of great changes. This article asserts the need to reassess the philosophy, content, and structure of graduate training in preventive medicine. The field of preventive medicine faces an identity crisis of its own making, trying to be everything to everybody. The need for funding to overcome the shortage of specialists remains a critical but difficult issue that demands innovative solutions. PMID- 1756064 TI - Medical Student Myopia Syndrome: a recently recognized pan-epidemic. PMID- 1756065 TI - War and the health of children. PMID- 1756066 TI - Resonance ionization spectroscopy for multiplex sequencing of tin-labeled DNA. AB - A method is described for synthesis of a tin reagent, triethylstannylpropanoic acid (TESPA), and its attachment to oligonucleotide primers. Except for the expected mobility retardation, the presence of [116Sn]-TESPA did not affect the sequencing ladder on electrophoresis gels. By using [120Sn]-TESPA and [35S]-dTTP simultaneously in the Sanger procedure, DNA bands on an electrophoresis gel were first located by autoradiography and then by resonance ionization spectroscopy to demonstrate the coincidence of the signals. Previous results using stable isotopes as labels on model compounds are now confirmed by their use in actual DNA sequencing products. PMID- 1756067 TI - An improved method for chromosome-specific labeling of alpha satellite DNA in situ by using denatured double-stranded DNA probes as primers in a primed in situ labeling (PRINS) procedure. AB - An improved primed in situ labeling (PRINS) procedure that provides fast, highly sensitive, and nonradioactive cytogenetic localization of chromosome-specific tandem repeat sequences is presented. The PRINS technique is based on the sequence-specific annealing in situ of unlabeled DNA. This DNA then serves as primer for chain elongation in situ catalyzed by a DNA polymerase. If biotin labeled nucleotides are used as substrate for the chain elongation, the hybridization site becomes labeled with biotin. The biotin is subsequently made visible through the binding of FITC-labeled avidin. Tandem repeat sequences may be detected in a few hours with synthetic oligonucleotides as primers, but specific labeling of single chromosomes is not easily obtained. This may be achieved, however, if denatured double-stranded DNA fragments from polymerase chain-reaction products or cloned probes are used as primers. In the latter case, single chromosome pairs are stained with a speed and ease (1 h reaction and no probe labeling) that are superior to traditional in situ hybridization. Subsequent high-quality Q banding of the chromosomes is also possible. The developments described here extends the range of applications of the PRINS technique, so that it now can operate with any type of probe that is available for traditional in situ hybridization. PMID- 1756068 TI - Heteromorphisms of pericentromeric heterochromatin of chromosome 19. AB - The pericentromeric heterochromatin of chromosome 19 exhibits considerable variation even by the G-banding technique. Nevertheless, the C-banding technique has been universally employed to investigate pericentromeric hetromorphisms. We demonstrate that optimal expression of the pericentromeric region can be achieved by using the AluI/G technique. The pericentromeric heterochromatin of chromosome 19 is classified into four classes (I-IV). Fifty normal individuals were evaluated and the incidence of types I-IV were 26%, 17%, 51%, and 6%, respectively. No consistent relationship was observed between the types of heterochromatin identified by the AluI/G technique when compared with the other routinely used procedures. PMID- 1756069 TI - A novel approach to the rapid isolation and nucleotide sequencing of genomic clones. AB - In this study, a genomic library subdivided into fractions was rapidly screened by a Southern detection technique. Deletion libraries were obtained from recovered genomic clones by single random cuts with nuclease S1. These deletion libraries proved useful for localizing genes in the inserts and yielded, after size fractionation, nested deletions suitable for nucleotide sequencing. An heterologous vector (pDB21) carried the insert used as probe for all hybridizations involved in the process of genomic clones isolation and characterization. PMID- 1756071 TI - A scientific review of the association between prone sleeping position and sudden infant death syndrome. PMID- 1756070 TI - Cot death: should the prone sleeping position be discouraged? PMID- 1756072 TI - The association between the prone sleeping position and sudden infant death syndrome (SIDS): an editorial overview. PMID- 1756073 TI - An analysis of trends in the incidence of sudden infant death in The Netherlands 1969-89. AB - There is considerable interest in the relationship between sleeping position and the occurrence of sudden infant death syndrome (SIDS). As changes have been reported in The Netherlands in the position infants have been placed to sleep, the national Dutch sudden infant death rates were analyzed over the time that such changes have taken place. The overall post-perinatal death rate (1 week less than 1 year) was around 4-4.5 per 1000 live births from 1969 until 1985. From 1985 until 1989 the rate fell from 4.1 to 2.9 per 1000 live births. During the same period the cot death/SIDS rate rose from 0.44 per 1000 in 1969 to between 1.08 and 1.31 per 1000 in 1977-87, and subsequently fell to 0.7 per 1000 in 1989. These trends coincided with changes in prone sleeping position demonstrated in national surveys. The problems of interpreting such national data, with only 50 60% of infant deaths being autopsied and with the possibilities of misclassification over time, are fully discussed. The data are supportive of the relationship between prone sleeping position and cot death. PMID- 1756074 TI - Prone sleeping position and SIDS: evidence from recent case-control and cohort studies in Tasmania. AB - The most recent data from the cohort and case-control studies of SIDS and prone position recently reported from Tasmania are reviewed. The cohort analysis was based on 4103 infants born between 1 January 1988 and 1 December 1990 assessed as being at high risk at birth, of whom 29 later died of SIDS. A matched analysis which controlled for infant birthweight and maternal age indicated that prone sleeping position was associated with an increased risk of SIDS (OR 3.92, 95% Cl [1.37-11.24]). The case-control study was based on all (n = 55) Tasmanian SIDS death from October 1989 to April 1991 and matched live controls. The unadjusted odds ratio for prone position and SIDS was 5.04 (95% Cl [2.29-11.11]). The population attributable risk percentage, based on the high risk cohort data, was 0.38 (95% Cl [0.35-0.41]), suggesting that a significant reduction in SIDS incidence might occur if the prevalence of the prone sleeping position in the infant population were reduced. Other factors which may be important for the development of any public health interventions to reduce SIDS based on these findings are discussed. PMID- 1756075 TI - A review of epidemiological studies of sudden infant death syndrome in southern New Zealand. AB - The rate of sudden infant death syndrome (SIDS) in Southern New Zealand has been very high with an apparent real increase in incidence from the early 1970s. Recent research is reviewed and the results of specific interventions aimed at preventing SIDS summarized. The intervention consisted of strongly advising new parents that their babies sleep on their back or side and that they avoid over heating, especially during infections. For the Otago area, child-care practice has been documented and prone sleeping of 1 month old babies has declined from 41.8% in 1986 to 2.4% in 1989-90. There is also evidence that parental control of infants' thermal environment has improved, maternal smoking during pregnancy has slightly decreased and the number of babies breast fed at 1 month of age has increased by 11%. In Southern NZ there has been a decline in post-neonatal SIDS mortality from 6.3 deaths per 1000 live births 1979-84 to 1.3 per 1000 live births in 1990. There are grounds for supposing that the intervention has been causative of this change, a possibility being addressed by on-going studies. PMID- 1756076 TI - The pneumographic and medical investigation of infants suffering apparent life threatening episodes. AB - Investigation of 340 babies who suffered from apparent life threatening episodes (ALTE) was performed using pneumographic studies and a variety of medical investigations. A number of medical abnormalities were demonstrated by history or investigation, including gastro-oesophageal reflux (211), airways pathology (17), evidence of fits (25), brain-stem tumour (2), hypoglycaemia (2), respiratory syncytial virus (8) and possible Munchausen by proxy (5). Pneumographic abnormalities were detected in 27 of the 340 infants. Home monitors were used for 135 infants. Future central apnoeas occurred in 20 of the 26 infants on home monitors that had had an abnormal pneumogram, compared with one of the 109 infants on home monitors after a normal pneumogram. Thus pneumograms have a sensitivity and specificity of 95% for predicting central apnoeas in babies who have already suffered an ALTE. The effect of eyeball pressure on the heart rate was measured in 65 babies and was found to cause a brisk drop in heart rate in 32 babies. Twenty-two of the 32 babies had future white apnoeas (usually associated with gastro-oesophageal reflux), compared with five of the 33 babies who had no drop in heart rate in response to eyeball pressure. Thus this test has a sensitivity of 81% and a specificity of 74% at predicting white apnoeas in babies who have already suffered an ALTE. PMID- 1756077 TI - Resource allocation in contemporary paediatrics: the case against high technology. AB - High technology has introduced a new dimension to medical treatment. There are inevitable social costs as well as benefits, and the allocation of resources to high technology, as opposed to other areas of health care, is a contentious issue. The current balance in health service funding between high technology and low technology is not appropriate. It is driven by the technological imperative and only offers solutions to a limited number of problems. There is a scarcity of health resources left to develop intersectoral responses and provide adequate funding for research into person-intensive interventions suitable for many problems. Arguments against allocating too many resources to high technology in paediatrics are examined in this paper. PMID- 1756078 TI - Herpes simplex virus type 1 infections presenting at birth. AB - Two cases of intra-uterine acquired neonatal herpes simplex type I presented with atypical skin lesions apparent at or shortly after birth; the timing and appearance of the lesions meant that herpes virus infections were not considered to be the most likely diagnosis. Once herpes simplex was diagnosed, both infants were treated with acyclovir. Prompt diagnosis and institution of acyclovir are imperative for a favourable outcome from neonatal herpes infections. PMID- 1756079 TI - Cord whole blood hyperviscosity: measurement, definition, incidence and clinical features. AB - Cord whole blood viscosity and haematocrit values (PCV) were determined in 2461 live birth infants. Viscosity measurements were performed on an Australian designed coaxial narrow-gap viscometer. Normal viscosity values were determined for each week of gestation above 34 weeks. Hyperviscosity was defined as a viscosity value above 2 s.d. from the mean for each week of gestation and it occurred in 164 (6.7%) newborn infants. Although a close relationship existed between cord whole blood viscosity and PCV (r = 0.6597, P less than 0.0001), only 47.4% of polycythaemic infants (PCV greater than 65) were also hyperviscous and only 23.9% of hyperviscous infants were also polycythaemic. Hence, using the haematocrit to select which infants require viscosity studies fails to detect many hyperviscous newborn infants. Hyperviscosity was less common (3.6%, P less than 0.001) in infants who were born by Caesarean section and more common (16.5%, P less than 0.001) in those who were growth retarded. Of the hyperviscous infants, 84.5% were not growth retarded, most (87.8%) were term and most (86.6%) were delivered vaginally. Most hyperviscous newborn infants may thus remain undetected unless routine whole blood viscosity studies are performed. PMID- 1756080 TI - The use of dexamethasone in full-term infants with severe respiratory failure and pulmonary barotrauma. AB - Eight full-term infants (mean gestation 39.9 weeks [range 37-42] and mean birthweight 3642 g [range 3060-4200]) with severe respiratory failure (median oxygenation index 28 [range 16-65] and median arterial/alveolar PO2 ratio (a/APO2) 0.094 [range 0.038-0.165]) and pulmonary barotrauma were treated with Dexamethasone, 0.5 mg/kg per day, from the median age of 5 days (range 3-22). Six of the eight (75%) infants survived. They were weaned from mechanical ventilation and extubated a median of 2.5 days after commencing treatment with Dexamethasone. Two infants died and one of them suffered recurrent pneumothoraces. There was a significant improvement in oxygenation in the seven infants who survived the 72 h period of observation. Their median oxygenation index was 24 when Dexamethasone was commenced compared with 8 after 12 h (P less than 0.05) and 10 after 36 h (P less than 0.025). Their a/APO2 ratio was 0.095 when Dexamethasone was commenced compared with 0.289 after 12 h (P less than 0.05) and 0.207 after 36 h (P less than 0.025). There was a significant increase in the infants' arterial mean blood pressure associated with Dexamethasone therapy and one infant developed Staphylococcus aureus septicaemia. In this uncontrolled study of eight full-term infants with severe respiratory failure and pulmonary barotrauma, the use of Dexamethasone was associated with significant improvement in oxygenation and rapid weaning from mechanical ventilation. PMID- 1756081 TI - Intravenous indomethacin therapy in preterm neonates with patent ductus arteriosus. AB - This study examined the response of the patent ductus arteriosus (PDA) to intravenous Indomethacin using serial two dimensional and Doppler echocardiography and documented the complications associated with therapy. Thirty six preterm neonates who were oxygen and ventilator dependent were studied when they were aged 3-7 days. The PDA initially closed in 22 (61%) and constricted in seven (19%) of the infants. It was non-responsive in five (14%) and the treatment was stopped because of complications in two (6%). Only three (43%) of seven neonates given a second course had PDA closure. In the 25 instances where there was PDA closure following Indomethacin, re-opening was documented echocardiographically on three (12%) occasions. Overall, Indomethacin therapy was successful in 29 (81%) neonates, PDA ligation was required in four (11%) and three died from unrelated causes. Three (8%) neonates developed major complications: multiple gastric perforations in the first, focal ileal perforation in the second, and necrotizing enterocolitis in the third. Treatment failure, PDA ligation and major complications occurred exclusively in neonates less than 28 weeks gestation. In view of the relatively low efficacy and high major complication rate in these extremely preterm infants, a randomized clinical trial needs to be conducted using two dimensional and Doppler echocardiography to allow accurate assessment of the PDA response to intravenous Indomethacin. PMID- 1756082 TI - Glucose-6-phosphate dehydrogenase enzyme activity in normal, hemizygote and heterozygote Kelantanese Malays. AB - This prospective study was performed to quantify glucose-6-phosphate dehydrogenase (G6PD) enzyme activity in deficient males and female heterozygotes. The methods used in the study were the fluorescent spot test, G6PD enzyme electrophoresis on cellulose acetate and quantitative assays. Forty-seven children who had been detected as spot screen deficient at birth were rescreened. Their first degree relatives were also included in the study. The mean enzyme activity of deficient males was 0.74 iu/g Hb (s.d. +/- 0.8), of female heterozygotes was 6.5 iu/g Hb (s.d. +/- 3.2) and of normal males was 12.1 iu/g Hb (s.d. +/- 3.5). The mean activity in deficient males was 6.1% of normal males. Most (35 of 47) of these fell into class 2 in Beutler's classification of G6PD variants. This indicates a population which may be susceptible to favism. Female heterozygotes had an intermediate enzyme activity with a wide scatter. Using a cut off point of enzyme activity of below 9.0 iu/g Hb gave sensitivity and specificity of 87% and 84% in detecting female heterozygotes. This group could be defined more accurately by combining quantitative assays with family studies. PMID- 1756083 TI - Survival, growth and quality of life in children after orthotopic liver transplantation: a 5 year experience. AB - The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages less than 1, 1-5 and greater than 5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight less than -1 was 57%, greater than -1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 +/- 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth. PMID- 1756084 TI - Family adaptation to a child's chronic illness. PMID- 1756085 TI - Disaster nursing. PMID- 1756086 TI - Nurse anesthesia care. PMID- 1756087 TI - Occupational health nursing education. PMID- 1756088 TI - Mentorship. PMID- 1756089 TI - Alzheimer's disease. AB - This chapter has included a review of nursing research in Alzheimer's disease. Much of what is in the literature regarding nursing of Alzheimer's disease patients and their families is anecdotal and has not been validated by systematic research and is atheoretical. The majority of nursing research on Alzheimer's disease has been focused on patient characteristics and problem behaviors or on the needs and experiences of family caregivers. Research should continue in these areas along with testing nursing interventions to maintain optimal cognitive, physical, social, and emotional function of Alzheimer's disease patients. Explanatory theories should be devised and tested to advance the development of nursing knowledge in the care of Alzheimer's disease patients and family caregivers. Finally, more evaluation research is needed to test the cost effectiveness of home-based and institutional programs, including effects on Alzheimer's disease patients, family members, and staff caregivers. PMID- 1756090 TI - Nutritional studies in nursing. PMID- 1756091 TI - Health conceptualizations. PMID- 1756092 TI - Arthritis. PMID- 1756093 TI - Human responses to catastrophe. PMID- 1756094 TI - Family caregiving for the elderly. PMID- 1756095 TI - In vitro assessment of stereoselective hepatic metabolism of disopyramide in humans: comparison with in vivo data. AB - Metabolism of disopyramide (DP) enantiomers has been investigated in primary cultures of adult human hepatocytes. Results were compared with in vivo data obtained from a previous pharmacokinetic study (Le Corre et al. Drug Metab. Dispos. 16:858-864 1988). Metabolism of DP enantiomers as a function of incubation time showed constant velocity over time. The intracellular/extracellular distribution of both DP and mono-N desisopropyldisopyramide did not appear to be stereoselective. Metabolism of DP enantiomers as a function of substrate concentration followed a first order kinetics. The average fractions of (-)-(R)-DP and (+)-(S)-DP metabolized in vitro (4.7 +/- 2.7 and 7.1 +/- 4.2%, respectively, n = 4) were about 5-fold lower than the fractions metabolized in vivo (26.0 +/- 6.0 and 40.2 +/- 8.8%, respectively, n = 6). The stereoselective index [(+)-(S)/(-)-(R)] of the N-dealkylation pathway obtained in vitro (1.51 +/- 0.11, n = 4) was very close to the one obtained in vivo (1.55 +/- 0.10, n = 6). These results highlight the interest of hepatocyte cultures in the evaluation of drug metabolism and especially in the assessment of stereoselectivity. PMID- 1756096 TI - Interaction of pirprofen enantiomers with human serum albumin. AB - The interaction of pirprofen enantiomers with human serum albumin (HSA) was investigated by means of high-performance liquid chromatography (HPLC), circular dichroism (CD), and 1H NMR spectroscopy. HPLC experiments indicated that both pirprofen enantiomers were bound to one class of high-affinity binding sites (n(+) = 1.91 +/- 0.13, K(+) = (4.09 +/- 0.64) x 10(5) M-1, n(-) = 2.07 +/- 0.13, K(-) = (6.56 +/- 1.35) x 10(5) M-1) together with nonspecific binding (n'K'(+) = (1.51 +/- 0.21) x 10(4) M-1, n'K'(-) = (0.88 +/- 0.13) x 10(-4) M-1). Slight stereoselectivity in specific binding was demonstrated by the difference in product n(+)K(+) = (0.77 +/- 0.08) x 10(6) M-1 vs. n(-)K(-) = (1.30 +/- 0.21) x 10(6) M-1, i.e., the ratio n(-)K(-)/n(+)K(+) = 1.7. CD measurements showed changes in the binding sites located on the aromatic amino acid side chains (a small positive band at 315 nm and a pronounced negative extrinsic Cotton effect in the region 250-280 nm). The protein remains, however, in its predominantly alpha-helical conformation. The 1H NMR difference spectra confirmed that both pirprofen enantiomers interacted with HSA specifically, most probably with site II on the albumin molecule. PMID- 1756097 TI - An evaluation of ibuprofen bioinversion by simulation. AB - Using a pharmacokinetic model recently proposed to explain ibuprofen disposition in man, plasma concentrations of pure ibuprofen enantiomers were simulated following oral administration of (-)-(R)-ibuprofen, (+)-(S)-ibuprofen, or rac ibuprofen. Simulated and literature values for AUC's were used to compare S/R ratios for different cases of the model and for different methods of calculating the fraction of R bioinverted to S. Numerical simulation using STELLA confirmed previous results for different cases of bioinversion. Simulated S/R AUC ratios, for administration of the racemate, ranged from 4.0 (presystemic bioinversion) to 1.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 1.53 +/- 0.2 for administration of the racemate; therefore, systemic bioinversion was concluded to be representative of ibuprofen disposition. Additional simulations of S/R AUC ratios, for administration of (-)-(R)-ibuprofen only, ranged from 1.5 (presystemic bioinversion) to 0.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 0.50 +/- 0.9 for administration of (-)-(R)-ibuprofen only, which again supported conclusions of systemic bioinversion. Using different equations for estimation of fraction of R inverted to S (FR----S), results based on simulated data were identical; however, FR----S values based on literature data were different. Therefore, assumptions made for different FR----S equations do not appear to be rigorous. Calculations of FR----S, based on literature data, averaged 0.52 overall, indicating bioavailability of (+)-(S)-ibuprofen may be similar for a 150 mg dose of (+)-(S)-ibuprofen compared to a 200 mg dose of racemate. PMID- 1756098 TI - Food safety. Fish botulism, Hawaii. PMID- 1756099 TI - New estimates of maternal mortality. PMID- 1756100 TI - Yellow-fever vaccinating centres for international travel. Amendments to 1991 publication. PMID- 1756101 TI - Acquired immunodeficiency syndrome (AIDS). The STD/AIDS control programme. PMID- 1756102 TI - Expanded programme on immunization. Measles outbreak, Kampala. PMID- 1756103 TI - The "EMIO" way--a different approach to listing etiologies in differential diagnosis. AB - To introduce the early diagnosis concept in oncology to medical students as early as possible in their curriculum, in the Cerrahpasa Medical School, University of Istanbul, English-speaking section, weekly workshops were added to their regular courses in Record Taking and Differential Diagnosis in the third year (six-year curriculum). A different method was selected in listing possible etiologies of signs and symptoms, to emphasize early diagnosis of malignancies. This approach aimed to arouse more interest in students who were actively participating in the formation of these lists, which finally were compiled as a syllabus. PMID- 1756104 TI - A process for developing a curriculum in ethics and human values. AB - This article describes the process and results of the deliberations of the group of authors at the 1989 spring meeting of the Northeast Group for Educational Affairs. The participants worked under the premise that someone had given an unlimited amount of money to fund a new medical school. They had to select and define what the educational goals would be and produce a plan to help students reach these goals. There had to be an evaluation process that documented progress toward the stated goals. This paper describes the ethics and human values curriculum, which should be of interest to cancer educators. The knowledge, skills, values, and attitudes are defined and the four-year process of implementing the teaching is described. This curriculum-planning process is applicable to any aspect of cancer education--first defining the outcome, then the evaluation process, and finally, how to get to that outcome. PMID- 1756105 TI - The use of video tape in teaching how psychological factors influence nutritional status in chronic/terminal illness. AB - The medical students of Louisiana State University Medical School in New Orleans are required to take a clinical nutrition course in their senior year. In 1989, audio-visual media were used to introduce the students to the ways that the psychological aspects of chronic/terminal illness can influence nutritional status. In order to illustrate this topic, a patient with acquired immune deficiency syndrome (AIDS) was interviewed by a psychiatrist, internist, and a dietitian over several weeks. The interviews were videotaped and the videotape was edited to 25 minutes to address specific areas including psychiatric symptomatology, coping with illness, attitude towards treatment, diet and nutritional status, and results of the anthropometric and clinical exams. During the nutrition course, the videotape was presented to the students with subsequent discussion facilitated by the psychiatrist. The students agreed the subject was favorably presented and had increased their understanding of psychological factors in physical illness. The pre- and post-film examinations suggested the students were already aware of many of the psychological issues of chronic/terminal illness. The videotaped interview of a real person diagnosed with a chronic/terminal illness was found to be useful in introducing a difficult subject within a limited course schedule. PMID- 1756106 TI - Impact of a student interdisciplinary oncology team project. AB - Team approaches to health care have been developing steadily over the past 30 years in response to increasing concerns about accessibility, efficiency, and comprehensiveness of health care services. Implementation of team approaches has been accompanied by development of curricula and educational experiences that educate health professionals both in effective teamwork skills and in understanding the contributions each profession makes to comprehensive health care. Such a project was implemented in 1975 at the University of Hawaii involving the Schools of Nursing, Social Work, and Medicine. This paper describes an evaluation of the impact of an interdisciplinary team approach to the care of oncology patients by students in medicine, nursing, and social work. Evaluation is based upon project objectives using a series of pre- and posttest measures and weekly logs by participating students between 1979 and 1985. The paper addresses the following questions: What was the impact of the team experience on participating students as reflected in evaluation data? How effective was the Student Interdisciplinary Oncology Team Project in helping students achieve each of the seven stated objectives? What are the differences in professional socialization processes among the three professions represented in the project? PMID- 1756107 TI - Use of a modified Delphi technique to guide coordination of cancer education in Texas medical schools. AB - Delphi technique is a method of structuring group communication and is useful in achieving consensus on goals, plans, or positions. The Delphi technique was used to determine a course of action to enhance cancer education at each of eight medical schools in Texas. Participants in this study were deans of medicine and a faculty member considered to be the lead cancer expert in the curriculum. A three generation Delphi study was conducted with the deans using a telephone interview, a personal interview, and a conference of participants, including cancer experts. The Delphi technique was found to be an effective approach for increasing awareness of the statewide cancer plan, for involving all medical schools in achieving the goals of the plan, and for identifying means for enhancing cancer education at each medical school. A consensus was reached to develop a statewide standardized assessment of graduating medical students' knowledge about principles of cancer prevention and screening. The results could serve as a means of determining cancer education needs at each medical school. PMID- 1756108 TI - Teaching specialty cancer medicine in rural hospitals: the cancer outreach program as a model. AB - Cancer doctors and nurses are clustered in the metropolitan areas of Virginia. However, cancer patients are found throughout the state, and cancer mortality time trends are worse in the rural areas. Efforts to recruit cancer physicians and nurses to rural hospitals have been unsuccessful due to the practice characteristics, educational isolation, and economic disincentives. Our rural cancer education program involves the physicians and nurses currently in practice at two rural hospitals. We provide hands-on training in cancer care, continuing education, and intense week-long educational sessions. We have observed changes in physician and nurse practice styles that benefit the cancer patient including effective pain management, enrollment of patients on clinical trials, increased use of adjuvant therapy, and breast conservation. We are providing state-of-the art cancer care at the rural hospitals in the Cancer Outreach Program. We have improved the educational opportunities and increased utilization of the resources of the academic career center. We can modify the practice characteristics by providing needed clinical programs and enhancing the rural hospital/academic medical center link. We have shown that rural cancer care can be revenue-neutral or positive, and we are seeking creative solutions to the financial disincentives of rural specialty practice. We can assist the rural hospital in the recruitment of oncology specialty nurses and physicians by providing cancer care services, and the patient caseload is available to teach prospective rural subspecialty practitioners at the rural hospitals. PMID- 1756109 TI - Risk profiles of women with cervical neoplasia. AB - Risk-factor profiles were compared in M.D. Anderson Cancer Center patients with various uterine cervix histologic diagnoses. Intraepithelial neoplasia (n = 171) and condyloma (n = 82) were associated with significantly lower patient age (mean 23.6 and 25.8 years, respectively). In addition, these two groups were lowest in annual income, age at beginning intercourse and at first pregnancy, and highest in percentages of black and Hispanic patients, number of sexual partners, and history of gonorrhea. Women with squamous carcinoma in situ (n = 47), who were about a decade older, exhibited a similar socioeconomic distribution and sexual history. All three groups also reported high prevalences of current smokers, were most likely to use oral contraceptives, and were least likely to use diaphragms or condoms. Patients with invasive squamous cell carcinoma (n = 77) had a mean age of 46.3 years, a large lowest-income constituency, and the highest mean number of pregnancies; they were least likely to have used oral contraceptives. Adenocarcinoma (n = 21) was epidemiologically distinct: a predominance of white woman characterized by high socioeconomic status, elevated body mass index, and non of the liberal sexual practices of the other groups. Primary and secondary prevention strategies must be tailored to the unique needs and socioeconomic status of the young at-risk populations. PMID- 1756110 TI - Primary prevention of malignant melanoma in a Swedish urban preschool sector. AB - Malignant melanoma is the most rapidly increasing tumor in Sweden. Sunburns in childhood are considered a major risk factor. In the spring of 1989, a health education program was therefore initiated in Stockholm County in cooperation with the local preschool authorities in the area. Lectures on malignant melanoma, hazards of sunburns in childhood, and the importance of sun awareness were arranged for the nursery school matrons in the preschool sector. Thirty-five of 42 authorities (83%) wanted a lecture for their nursery school matrons, whereas 17% of the authorities wanted to spread information on their own. Of 1,991 nursery schools, 1,783 (90%) took part in the information program. These, the Stockholm nonparticipants, and the rest of the country received written information from the Federation of Swedish Municipalities by initiative of the Department of Cancer Prevention. A questionnaire distributed to 574 randomly selected nursery schools in Stockholm county and to 100 in a reference area outside Stockholm showed that sun awareness was reported high in both places. Face-to-face information disseminated by an established organization was more effective in increasing sun awareness in the preschool sector than mailed information alone. In the areas where lectures were given, the message of sun awareness practice was passed on to nursery school staff and parents twice as effectively as in the reference area (p less than 0.01). PMID- 1756111 TI - Information needs of families of cancer patients: a literature review and recommendations. AB - This paper reviews evidence on the kinds of information needed by family members of cancer patients, discusses why families frequently lack needed information, and suggests strategies for meeting their information needs. Studies reviewed show that families' needs for information are substantial and that a large percentage of family members feel that these needs have not been adequately met by health care providers. This lack of needed information negatively affects the patient's care as well as the physical, psychological, and social well-being of family members. Strategies for addressing this problem include wider distribution of generic information about cancer and treatments to family members as well as developing standard professional procedures for making information about a patient's clinical condition available to family members. PMID- 1756112 TI - Diacylglycerol-induced melanogenesis in Skh-2 pigmented hairless mice. AB - We investigated the effect of topically applied diacylglycerols (DG) on melanogenesis in Skh-2 pigmented hairless mouse skin. Groups of mice were treated according to 4 different regimens of either 1,2-dioctanoyl-sn-glycerol (DOG) or 1 oleyl-2-acetyl-sn-glycerol (OAG) with or without ultraviolet irradiation (UVR). After the treatment regimens were completed, separated epidermal tissue was stained with L-dopa and thin sections of whole skin were stained by the Warthin Starry method to detect melanin deposition. Quantification of the stained areas by digital image analysis disclosed that DOG treatment without UVR increased the dopa-positive area in skin in a dose-dependent manner but had no effect on melanin deposition. DG treatment acted synergistically with UVR to enhance melanogenesis, with synergism being more pronounced for melanin deposition than for dopa staining. DOG treatment prior to UVR also resulted in an enhanced melanogenic response to UVR, suggesting that DG increases the sensitivity of melanocytes to subsequent UVR by inducing dopa oxidase activity. OAG also enhanced UVR-induced melanogenesis in a dose-dependent manner and was at least as potent an inducer as was DOG. Because DG is known to activate protein kinase C, our results suggest that a protein kinase C-dependent process is involved in melanogenesis. PMID- 1756113 TI - Photopatch testing with different ultraviolet A sources can yield discrepant test results. AB - A photopatch test series consisting of 27 substances was tested in 81 patients with suspected photosensitivity disorders. Irradiation was performed using the following light sources: TL-K 40W/09 bulbs (UVA'; lambda max. at 355 nm), UVASUN 5000 (UVA''; lambda max. at 375 nm), and TL 20 W/12 bulbs (UVB; lambda max. at 315 nm). One day after applying 4 sets of the test substances (D1), one test series each was exposed to 10 J/cm2 of UVA' or UVA'', or a combination of 40 mJ/cm2 UVB and 10 J/cm2 UVA''; the fourth series was left nonirradiated (control). Photopatch test reactions (PPTR) were defined as positive if there was at least an indurated erythema on D3 or later between D3 and D21 (late-onset reactions) exclusively at the irradiated, but not at the control site. At least one positive PPTR was found in 35 patients (43%), 7 of whom exhibited late-onset reactions only; in 2 cases the tests could not be read because of skin irritation. On D3, there were 44 positive reactions with UVA', only 10 of which were also demonstrable with UVA''. Twenty-one late-onset PPTR were found with UVA' and 17 with UVA''. Late-onset reactions elicited by UVA' or UVA'' mostly were concordant; divergent positive or negative results were found only in a few cases. Compared with the results obtained with UVA' or UVA'' alone, combined irradiation with UVB and UVA'' occasionally led to divergent positive as well as negative results. When photopatch test results are interpreted, it should be considered that testing with different UVA sources may yield divergent results. PMID- 1756114 TI - Chronic actinic dermatitis: a time course study of histopathological changes. AB - We report herein a case of chronic actinic dermatitis in which histopathological changes were observed on several occasions during the course of 2 years. The findings were quite different among stages of the eruption. At a half year after the appearance of the lesion, histological findings revealed eczematous changes. However, gradually a granulomatous change appeared with histiocytes and giant cells. Although the mechanism of histogenesis is not clear, the appearance of histiocytic giant cells seems to be unusual in chronic actinic dermatitis. PMID- 1756115 TI - The hairless guinea pig as an experimental animal for photodermatology. AB - Photobiologic reactions to various modalities of ultraviolet light (UVL) irradiation were evaluated in the recently identified hairless guinea pig, Crl: IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro- and microscopically. The animal developed similar but somewhat stronger reactions than the Hartley guinea pig to the UVB irradiation and topical and systemic PUVA treatments. The density of the epidermal Langerhans cell of the hairless guinea pig was significantly higher than that of the hairy strain. The photoallergic contact sensitization was easily induced by tetrachlorosalicylanilide. These results indicate that the hairless guinea pig can be used as an animal model for photobiologic and photoimmunologic investigations. PMID- 1756116 TI - Ultraviolet light hardening in polymorphous light eruption--a controlled study comparing different emission spectra. AB - Polymorphous light eruption (PLE) is a common disorder characterized by a delayed, abnormal response to ultraviolet (UV) radiation, with a varied morphology of itching efflorescences on sun-exposed areas of the skin. Thirty-one PLE subjects were treated with either UVA (340-400 nm) or UVA and UVB (300-400 nm) phototherapy during spring 1987 (10 exposures to UV light). They were randomly allocated to these 2 groups. For subjects of the UVA group, the applied dose corresponded to their individual minimal tanning dose; for subjects of the UVA and UVB group it corresponded to approximately 3/4 of their individual minimal erythema dose. The sun protection effect was studied by a high dose of UVA (80-160 J/cm2; 340-440 nm) after the treatment period, by analysing the histidine content of the stratum corneum and the urocanic acid photoisomerization, and by evaluating the subjects' diaries. The patients were asked to expose their skin to sunlight at least 3 times after UV hardening in the following 2-10 weeks. The results of both the UVA provocation and of the natural sun exposure confirmed the success of UV hardening without the occurrence of severe side effects. The content of histidine and of its metabolite urocanic acid in stratum corneum was significantly increased during the treatment. These data are interpreted to be biochemical markers for improved sun protection. PMID- 1756117 TI - Age-related changes in photosensitivity and cellular sensitivity to ultraviolet B in a xeroderma pigmentosum group E patient. AB - Skin phototesting and cellular sensitivity studies were performed in a patient with xeroderma pigmentosum (XP) complementation group E (XP80TO) at the ages of 50 and 55 years. She showed a reduced minimal erythema dose at both ages, but the dose at age 55 was much lower than that at age 50 when tested with monochromatic ultraviolet (UV) light (280, 290 and 300 nm). The cellular sensitivity to UVC (254 nm), UVB and UVA and UVC-induced unscheduled DNA synthesis were examined using fibroblasts obtained by skin biopsy at the ages of 50 and 55 (XP80TO-1 and XP80TO-2, respectively). DNA synthesis was similar in both cell lines. XP80TO-2 cells were more sensitive to UVB cytotoxicity than XP80TO-1 cells in both the dividing and quiescent phases, but both cell lines exhibited a similar sensitivity to UVC and UVA. These results suggest that the in vitro cellular sensitivity to UVB may correlate with the clinically observed erythema reaction. Further, the results suggest that some XP complementation group E cases at least may show an increase in photosensitivity in vivo and in vitro with aging. PMID- 1756118 TI - Angelica-induced phytophotodermatitis. PMID- 1756119 TI - Effect of visible light irradiation on human epidermal Langerhans cell membrane marker defined by monoclonal antibody (Leu 6). PMID- 1756120 TI - Effect of ultraviolet irradiation on Langerhans cells in mast cell-deficient W/WV mice. PMID- 1756121 TI - Effect of ultraviolet (UV) radiation and UVB-absorbing sunscreen ingredients on 7,12-dimethylbenz(a)anthracene-initiated skin tumorigenesis in hairless mice. PMID- 1756122 TI - [Patau's (trisomy 13) and Edwards' (trisomy 18) malformation syndromes]. PMID- 1756123 TI - [The third world and tuberculosis]. PMID- 1756124 TI - [Karl Klinke (1897-1972)]. PMID- 1756125 TI - [Nursing and psychosocial care of patients with homozygote beta-thalassemia]. PMID- 1756126 TI - [Organization of study courses "Nursing management and nursing science for nursing personnel. An explanation]. PMID- 1756127 TI - [Healthpolitical list of requirements for the consolidation of preventive pediatrics in Germany. Proposal by the Association of Pediatricians for the installation of a pediatric section at the Federal Ministry of Health]. PMID- 1756128 TI - [First event in continuing education at the Gelsenkirchen Urban Pediatric Hospital]. PMID- 1756129 TI - [First mobile pediatric home nursing in Bavaria--one year after its beginning]. PMID- 1756131 TI - Focused issue on myocardial stunning. PMID- 1756130 TI - Stunning of the myocardium: an update. AB - When severely ischemic myocardium is reperfused, prolonged myocardial dysfunction -a phenomenon named myocardial stunning--frequently occurs. Stunning also occurs in a variety of other situations. These include myocardium located adjacent to infarcted tissue, transient increase in myocardial O2 demands in the presence of incomplete coronary obstruction, during both systole and diastole, in isolated perfused hearts rendered ischemic or anoxic, and in a variety of clinical situations, such as following ischemic arrest in cardiac surgery, thrombolytic reperfusion, and after episodes of severe ischemia in Prinzmetal's angina or unstable angina. Although the fundamental mechanism(s) responsible for myocardial stunning has not been elucidated, in experimental preparations calcium antagonists, free-radical scavengers, and neutrophil depletion have each been found to be helpful in minimizing it. PMID- 1756133 TI - Clinical relevance of myocardial "stunning". AB - Experimental studies have demonstrated that myocardium reperfused after reversible ischemia exhibits prolonged depression of contractile function ("stunning"). Despite the multiplicity of clinical situations in which myocardial stunning would be expected to occur, investigation of this phenomenon in humans has been hindered by several major problems, including the limited accuracy of the methods available to measure regional left ventricular function, the inability to quantify regional myocardial blood flow during acute ischemia, the difficulty in establishing with certainty, the beginning and end of an ischemic episode, and the uncontrolled influence of variables (such as preload, afterload, adrenergic tone, and inotropic therapy) that have a major impact on postischemic dysfunction. The main problem is to discern whether a reversible defect of contractility is caused by stunning, silent ischemia, or hibernation (i.e., chronic ischemia). This differential diagnosis requires the simultaneous measurement of regional myocardial function and flow, which thus far has not been generally possible. Despite these limitations, however, numerous clinical observations suggest that stunning does occur in various settings in which the myocardium is exposed to transient ischemia, including coronary angioplasty, exercise-induced angina, angina at rest (unstable or variant), acute myocardial infarction with early reperfusion, open-heart surgery, and cardiac transplantation. Recognition of this entity is important, amongst other reasons, because it is likely to cause significant morbidity and because it is potentially correctable with inotropic therapy or even preventable with antioxidant therapy. In addition, the appreciation of the phenomenon of myocardial stunning should allow the clinician to assess the efficacy of reperfusion therapy with greater accuracy and to recognize that patients should not be denied mechanical revascularization solely because of an abnormal left ventricular wall motion. Perhaps the most intriguing clinical implication of the concept of myocardial stunning is the possibility that in patients who exhibit frequent episodes of ischemia in the same territory, the myocardium may not be able to fully recover between episodes and thus may remain reversibly depressed for prolonged periods of time, or even chronically, which could account for some cases of "ischemic cardiomyopathy." Our understanding of myocardial stunning in humans is still relatively crude and will not significantly improve until studies are performed that measure simultaneously regional myocardial perfusion and function (so that stunning can be differentiated from silent ischemia and hibernation). Future important areas of research should also include the elucidation of whether stunning can become chronic and the evaluation of therapies (such as antioxidant treatments) designed to prevent this contractile abnormality.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756134 TI - Pathogenetic role for calcium in stunning? AB - Cellular calcium homeostasis is disturbed during brief periods of ischemia, with free cytosolic Ca ([Ca2+]i) rising severalfold within 10-15 minutes (or even sooner). Nevertheless, the myocardial cells' ability to regulate Ca recovers quickly after reperfusion, unlike the lingering depression of contractile function known as stunning. This brief commentary considers the hypothesis that the rise in cell calcium during ischemia and during early reperfusion leaves behind stunning as an unwelcome legacy. This idea by no means excludes the involvement of other factors, such as free radicals; instead, it suggests a possible common pathway for cell injury by a variety of specific agents. A provocative feature of the formulation is the idea that the crucial lesion in stunning occurs at the level of the contractile proteins, rather than more proximally. PMID- 1756132 TI - Stunning: a radical re-view. AB - The recovery from trauma, whether ischemia or some other form of tissue injury, is never instantaneous; time is always required for repair and the return of normal metabolism and function. To what extent the delay in recovery of contractile activity (stunning) after a brief period of ischemia represents convalescence from ischemia-induced injury, as opposed to the expression of reperfusion-induced injury, is perhaps not as clear as the proponents of stunning would hope. Definitive evidence for a distinct reperfusion-induced pathology, which compromises the recovery of contractile function from the depressed state induced by ischemia, is elusive. If reperfusion-induced injury accounts for a significant proportion of stunning, then the molecular mechanisms responsible for initiating the event and those responsible for orchestrating the event at the level of the contractile protein are far from clear. Perturbations of calcium homeostasis are frequently cited as responsible for the depressed contractile state, however, some metabolic derangement must precede any pathologically induced ionic disturbance. In this connection, evidence indicates that free radical-induced oxidant stress, during the early moments of reperfusion, may modify the activity of a number of thiol-regulated proteins that are directly, or indirectly, responsible for controlling the movement of calcium. Sarcolemmal sodium-calcium exchange and the calcium release channel of the sarcoplasmic reticulum may be activated, whereas the sarcolemmal calcium pump and sodium potassium ATPase, together with the calcium pump of the sarcoplasmic reticulum, may be inhibited. Under the conditions prevailing during ischemia and reperfusion, this would be expected to promote an early intracellular calcium overload. It is difficult to reconcile such a change with the decreased inotropic state that characterizes stunning; however, it seems likely that the calcium overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium. It is still difficult to explain adequately the reduced inotropic state; clearly, the mechanism of stunning is not quite as simple as its definition. PMID- 1756135 TI - Postischemic stunning--the case for calcium as the ultimate culprit. AB - Two phases of the stunning phenomenon are proposed. The first causative phase occurs almost immediately with reperfusion and is thought to be associated with cytosolic calcium overload and an apparently normal or nearly normal mechanical function. Agents enhancing calcium influx, if introduced at this stage, may worsen subsequent stunning, whereas those inhibiting calcium influx may lessen the extent of subsequent stunning. The second phase, true stunning, is associated with established hypocontractility and responds favorably to agents enhancing calcium influx, whereas calcium antagonists further impair mechanical function when given at this stage. These patterns, derived from data obtained on isolated rat-heart studies, cannot directly be extrapolated to the large animal heart, such as that of the dog, where the presence of added circulating leukocytes may confound the issue and explain the apparently contradictory benefit of the late administration of calcium antagonists. The harmful effects of free radicals are not discounted but could be explained, at least in part, by multiple membrane damage, with a consequent rise of cytosolic calcium during the reperfusion period. PMID- 1756136 TI - Role of adenosine in the treatment of myocardial stunning. AB - Adenosine is an endogenous nucleoside produced from the breakdown of adenosine triphosphate (ATP) that possesses a number of complex cellular and metabolic effects that could ameliorate postischemic contractile dysfunction (myocardial stunning). Potential mechanisms include the repletion of high-energy phosphate stores, reduced myocardial oxygen consumption, a decrease in oxygen-derived free radicals, restoration of calcium homeostasis, and an increase in regional myocardial blood flow. Experimental studies have shown that adenosine can reduce myocardial stunning with or without a concomitant increase in the total myocardial ATP stores. Adenosine may be a useful pharmacologic strategy in the prevention and treatment of ventricular dysfunction following episodes of regional or global ischemia, although further studies are needed to clarify the precise cellular mechanisms involved. PMID- 1756137 TI - Do neutrophils contribute to myocardial stunning? AB - Although removal of neutrophils from the arterial blood by mechanical filtration has been reported to prevent or reduce the severity of myocardial stunning caused by a 15 minute coronary artery occlusion in the dog, neutrophil filtration does not protect against myocardial dysfunction following a 10-minute occlusion. Nonfilter methods to reduce neutrophil numbers or effectiveness with anti neutrophil serum, monoclonal anti-CD11b antibodies, or the lipoxygenase inhibitor nafazatrom fail to modify myocardial dysfunction after brief ischemia, even though they effectively reduce infarct size after more prolonged ischemia. The brief durations of ischemia required to produce myocardial stunning but to avoid necrosis are insufficient to produce local activation of complement, formation of chemotactic factors, or activation or infiltration of neutrophils. Microvascular plugging with neutrophils cannot be demonstrated in stunned myocardium, and abnormalities of microvascular function can be dissociated from impaired postischemic myocardial function. Based on the weight of accumulated evidence, neutrophils appear to have no important role in the production of stunned myocardium. PMID- 1756138 TI - Proclivity of activated neutrophils to cause postischemic cardiac dysfunction: participation in stunning? AB - Myocardial stunning is a reversible defect in contractile function provoked by brief episodes of ischemia followed by reperfusion. Many studies have demonstrated the potential involvement of free radicals in the etiology of myocardial stunning. While activated neutrophils have the capacity to release free radicals and evoke contractile dysfunction, it is not clear that this potential is realized in the absence of myocellular damage. Attempts to define the contribution of activated neutrophils to myocardial stunning by removing the cells from the bloodstream are contradictory, and the apparent simplicity of this seemingly logical approach is an illusion. For example, it is not known how many neutrophils are required to induce contractile failure, the site of action within the heart, the mechanisms that may be responsible, or even the time course or process of neutrophil activation. The production of free radicals and endothelial dysfunction may create conditions propitious for neutrophil recruitment. However, because activated neutrophils synthesize and release various mediators that are potentially toxic to myocardium, once the stage is reached for leukocyte accumulation, it may herald the progression from reversible to irreversible cardiac injury. PMID- 1756139 TI - Molecular mechanisms in "stunned" myocardium. AB - In a recent overview on stunning, Bolli listed the three pillars on which theories on stunning rest: its causation by oxygen radicals, the amplification of damage by Ca2+ overload, and the resulting excitation contraction uncoupling. Our own experiments with SOD and catalase do not convince us that stunning is caused by free radicals, because we and others were unable to show improvement. An important pathway of radical generation, i.e., xanthine oxidase, does not exist in the hearts of several families of mammals, but stunning can of course be produced in these species. We agree with Bolli that stunning represents a disturbance of electromechanical coupling, but we acknowledge the controversy that exists with regard to the subcellular seat of the defect. Our results would support hypotheses that pinpoint the defect to the sarcoplasmic reticulum. However, the possibility of multiple defects should also be considered: Our finding of altered Ca2+ ATPase expression and Kusuoka's finding of altered myofibrillar Ca2+ sensitivity are not necessarily mutually exclusive but may be complementary, or may represent different stages of ischemic damage. Our finding of decreased myosin expression may help to explain the long persistence of the contractile defect. From the available evidence, the hypothetial possibility evolves that stunning is not just an injury, but rather the unmasking of a regulatory mechanism to protect the heart against premature or further damage. The observation that coronary occlusion causes both stunning and preconditioning by a parallel, and not by a sequential, mechanism and that a multitude of genes alter their expression in order to protect the myocyte argue for a regulatory change. PMID- 1756140 TI - Preconditioning myocardium with ischemia. AB - Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stunning remains fully developed. Preconditioned, stunned, myocardium differs from control "virgin" myocardium in that adenine nucleotide content is reduced to about 50-70% of control, whereas creatine phosphate (CP) greatly exceeds normal- the so-called CP overshoot. When preconditioned myocardium is subjected to sustained ischemia, ATP utilization and anaerobic glycolysis occur at much slower rates than those observed in virgin myocardium. As a result of the early difference in metabolic rate, a longer period of ischemia is required for the ATP and lactate of the preconditioned tissue to reach the levels associated with irreversible injury. Associated with this change is a delay in myocyte death. The molecular events responsible for slower ischemic metabolism and associated tolerance of preconditioned, stunned tissue to a new ischemic episode are not known. Among the reactions that could cause a reduction in energy metabolism is reduced approximately P expenditure by stunned myocardium attempting to contract during the initial phase of ischemia. However, results from in vivo and in vitro experiments suggest that although stunning may be necessary for preconditioning to develop, it alone is not sufficient to cause preconditioning. Alternatively, metabolic changes may be explained by depressed activity of the mitochondrial ATPase during the episode of sustained ischemia. However, no direct experimental evidence supporting this hypothesis is available up to the present time. PMID- 1756143 TI - Oxidative metabolism in reperfused myocardium. PMID- 1756141 TI - Stunning: damaging or protective to the myocardium? AB - There are several potential outcomes of myocardial ischemia. When ischemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. Interventions aimed at reducing mechanical activity and oxygen demand, either before ischemia or during reperfusion, have been shown to delay the onset of ischemic damage and to improve recovery on reperfusion. When myocardial ischemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischemia, leading to a reversible, chronic left ventricular dysfunction, has been termed hibernating myocardium. Depression of mechanical activity is, actually, a protective mechanism whereby the hibernating cells reduce their oxygen demands in the setting of reduced oxygen supply. A third possible outcome after a short period of myocardial ischemia is a transient postischemic ventricular dysfunction, a situation termed stunned myocardium. As in the case of hibernating myocardium, the depressed contractile function occurring during stunning could be a protective mechanism, allowing the reperfused cells to gradually recover their metabolism and function. PMID- 1756142 TI - Calcium antagonists and stunned myocardium: importance for clinicians? AB - Experimental evidence indicates that calcium antagonists enhance the recovery of contractile function in canine myocardium stunned by a brief, 15-minute episode of transient coronary artery occlusion. In fact, both nifedipine and verapamil have been shown to improve systolic contraction, even when treatment was delayed, that is, when the agents were administered 30 minutes after reperfusion. The beneficial effects of delayed treatment were not a consequence of myocardial high energy phosphate preservation. Furthermore, as low-dose intracoronary nifedipine enhanced the recovery of function in the absence of systemic hemodynamic or coronary vasodilatory effects, the improved function associated with delayed administration of calcium antagonists could not be attributed solely to afterload reduction or increased coronary blood flow. These data suggest that calcium channel blockers exert a direct effect on the previously ischemic tissue, perhaps by subtle modulation of calcium transport or flux within the stunned myocytes. Although the precise mechanism of action of these agents remain unresolved, these intriguing experimental results raise the possibility that calcium antagonists may provide a clinically useful means of attenuating postischemic dysfunction of viable myocardium salvaged by thrombolysis, angioplasty, or cardiopulmonary bypass. The potential role of calcium-channel blockers in these clinical instances of stunned myocardium awaits further evaluation. PMID- 1756145 TI - A signal transduction through a unique rat T cell specific antigen, 8H3. AB - A signal transduction was detected in various rat T cells by cross-linking of 8H3 antigen by 8H3 antibody. A rat T cell proliferative response induced by 8H3 antibody is dependent on the presence of adherent cells. When spleen cells were cultured in the presence of 8H3 antibody, only CD4-positive T cell proliferation was induced. These proliferative CD4-positive T cells express rat interleukin 2 receptor, alpha chain. Cross-linking of 8H3 antigen resulted in an increase in cytoplasmic free Ca2+ in T cells and phosphorylation of a 120 kDa component of the 8H3 antigen. It should be noted that cross-linking of 8H3 antigen together with CD4 antigen but not with CD8 antigen by suboptimal doses of 8H3 and corresponding antibodies initiated the mobilization of [Ca2+]i. Furthermore, physical association of 8H3 antigen with TCR was demonstrated by comodulation of these two molecular complexes in some T cells. Thus, 8H3 antigen is involved in rat T cell transmembrane signal transduction. PMID- 1756144 TI - V(D)J recombinase activity in primary and secondary murine lymphoid organs: assessment by a PCR assay with extrachromosomal plasmids. AB - We developed a highly specific and sensitive polymerase chain reaction (PCR) assay to measure V(D)J recombinase activity using extrachromosomal plasmids and PCR. Extrachromosomal plasmids were prepared by eukaryotic replication origin, and a combination of the DQ52 and JH2 regions of the murine IgH gene, or of the D beta 2-1 and J beta 2.6 regions of the murine TCR beta gene, both with recombination signal sequences. Plasmids, transfected into cells to be examined and recovered after 48 h, were processed to detect recombined molecules by PCR with primers for the expected sequences produced by the precise signal joint. The PCR assay, when compared with a Camr assay that we prepared with the DQ52 and JH2 regions of the murine IgH gene, seems to have the following advantages. It detects only the recombined products produced by V(D)J recombinase activity and is therefore highly specific. It detects V(D)J recombinase activity in cells, including those with low replication frequency, which our Camr assay failed to do. This also enables detection of the recombinase activity not only in murine cell lines, but also in cells of murine lymphoid organs. The assay detects V(D)J recombinase activity in cell lines of human origin by replacing the eukaryotic replication origin of plasmids. High V(D)J recombinase activity was detected in bone marrow cells followed by thymic cells, and apparently lower activity was detected in cells of the lymph node and spleen of normal mice. PMID- 1756146 TI - Lymphokine-activated killer-cell-mediated killing of WiDr colon carcinoma cells is inhibited by K562 erythroleukemia cells. AB - Lymphokine activated killer (LAK) activity was induced in human peripheral mononuclear blood cells by human recombinant interleukin-2. Monocytes were required for optimal rapid proliferation of cells with LAK activity. They had no influence on the expression of tumoricidal activity by the LAK cells. The effector cells killed K562 erythroleukemia cells and WiDr colon cells differently, i.e. contact areas with WiDr cells were limited, whereas the contact areas between effector cells and K562 cells were much longer. Using mixtures of hot and cold target cells it was shown that effector cells preferably bind with K562 cells, impeding the binding of WiDr cells. Differences in expression of cytotoxicity of LAK cells against WiDr and K562 cells respectively was also observed after culturing the LAK cells for a relatively longer period. Cytotoxicity against WiDr was maximal at 3-16 days after starting LAK cell generation, whereas cytotoxicity against K562 was kept constantly high for at least 21 days. The addition of biological response modifiers [PHA and anti-CD3 antibody (OKT3)] during the LAK cell induction also had different effects on the expression of LAK activity against WiDr and K562 cells. Whereas PHA, in combination with rIL-2 had no significant influence on the cytotoxicity against WiDr cells, the cytotoxicity against K562 was significantly inhibited. Addition of anti-CD3 antibody diminished the cytotoxicity against WiDr target cells and had no influence on the cytotoxicity against K562 cells. PMID- 1756147 TI - Effects of fish oil on graft arteriosclerosis and MHC class II antigen expression in rat heterotopic cardiac allografts. AB - The effect of fish oil on accelerated graft coronary arteriosclerosis was assessed in Lewis to Brown-Norway rat heterotopic cardiac allografts. Twelve Brown-Norway rats were supplemented with 2 ml/kg/day of fish oil (68.3 mg eicosopentaenoic acid and 47.5 mg decosahexaenoic acid per milliliter). Eleven additional animals, receiving an isocaloric amount of safflower oil, served as control. All diets began 1 week before operation. Immunosuppression was obtained with low-dose cyclosporine (2 mg/kg/d). When killed (100 days), there were no significant differences in percentage weight gain, graft function, or histologic rejection score. Although lipid profiles were comparable, total cholesterol:high density lipoprotein ratio was marginally higher in animals treated with fish oil (p = 0.069). Mean percentage luminal occlusion (before and after correcting for differences in size between coronary vessels analyzed) and average intimal thickness were similar between animals treated with fish oil and safflower oil as assessed by computer-assisted digitized, morphometric planimetry. In all allografts, donor interstitial dendritic cells were repopulated with recipient dendritic cells. The major histocompatibility complex class II cell density in the fish oil group did not differ significantly from rats supplemented with safflower oil (1.48 +/- 0.68 vs 1.48 +/- 0.65 cells per mm2, p = 0.995). In conclusion, fish oil did not exert any beneficial effect over safflower oil in terms of graft coronary arteriosclerosis, histologic rejection, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756148 TI - Adjuvant native heart surgery during heterotopic heart transplantation: two case reports. AB - The results of heterotopic heart transplantation may be further improved if repairs on native heart abnormalities are performed just before implantation of the allograft. Such procedures increase the potential for the recipient's own heart to recover function and, thus, to maintain circulation if the heterotopic heart malfunctions or fails. The native hearts of two of our patients, both women, showed signs of greater contractility and ejection after repair and were able to provide adequate circulatory support during periods of donor heart failure. The first patient required ventricular aneurysmectomy and coronary artery bypass grafting, and the second, native mitral valve repair. Moreover, when persistent ventricular fibrillation occurred in the donor heart of the first patient, a donor cardiectomy was performed, and the recipient heart functioned well thereafter. As more adjuvant operations are performed and the results evaluated, we may find that heterotopic operations would be suitable in a greater variety of heart transplant candidates. PMID- 1756149 TI - Detection of asymptomatic myocardial ischemia in a heart transplant patient before sudden death. PMID- 1756150 TI - Prevalence and management of cholelithiasis in heart transplant patients. AB - There is no accepted approach in the field of heart transplantation for the management of asymptomatic cholelithiasis. To help formulate a strategy, we retrospectively reviewed the records of the 159 patients who underwent heart transplantation at our institution from March 1984 to January 1990. Information on the biliary tract was available in 141 (88.7%) of these patients. Before transplantation, 18 (11.3%) had undergone cholecystectomy. Of the 141, 99 (70.2%) had undergone ultrasonographic examination of the biliary tree: 74 (74.8%) had no gallstones seen on ultrasonograms; 8 (8.1%) had sludge; 16 (16.2%) had gallstones; and 1 had a probable polyp. Further information on the biliary tree by ultrasonography became available after transplantation in 24 of 42 patients who did not undergo ultrasonographic examination before transplant. After transplant, gallstones were found by means of ultrasonography or at autopsy in 13 more patients. Seven (4.4%) patients underwent cholecystectomy after transplant because of symptomatic cholelithiasis. Only one of these patients belonged to the group known to have gallstones before transplant. For the entire group, the prevalence of cholelithiasis was 29.6%. Multivariate analysis demonstrated that gallstones were significantly more common in older patients. We conclude that the prevalence of cholelithiasis in the heart transplant population is high but that only a minority of patients with asymptomatic gallstones will become symptomatic after heart transplantation. When they do, cholecystectomy may be safely performed. Prophylactic cholecystectomy and screening ultrasonography are not indicated in patients with asymptomatic cholelithiasis. PMID- 1756151 TI - Pseudoconduction of atrial flutter of a recipient atrium. AB - A nine-year-old girl had an episode of atrial flutter and a nonsustained wide QRS tachycardia during her initial hospitalization after orthotopic heart transplantation. Evaluation of her ECG and telemetric tracing revealed atrial flutter of the recipient atrium and sinus rhythm of the donor atrium. The wide QRS tachycardia was an accelerated ventricular rhythm that was also found on subsequent 24-hour ambulatory ECG monitoring. Timely recognition of recipient atrial arrhythmias prevents inappropriate clinical intervention. PMID- 1756152 TI - Coronary artery bypass two years after orthotopic heart transplantation: a case report. AB - Complete occlusion of the left anterior descending and right coronary arteries developed in a 58-year-old man 2 years after orthotopic heart transplantation. Because of his progressive shortness of breath, reversible myocardial ischemia, and decreasing ejection fraction, aortocoronary bypass was recommended. The operation was performed without complications, and his postoperative ejection fraction improved by more than 58%. In the past, when coronary artery disease developed in cardiac allografts, another transplant procedure was the only treatment option. Because of the limited donor hearts available today, new strategies are necessary for the treatment of cardiac allograft atherosclerosis. PMID- 1756153 TI - Progressive multifocal leukoencephalopathy fifty-seven months after heart transplantation. AB - Progressive multifocal leukoencephalopathy (PML), a subacute and usually fatal demyelinating disease of the brain, is caused by an opportunistic viral infection in immunocompromised patients. Only one case of PML after heart transplantation has been reported; it was discovered at the autopsy of a patient who died of multiorgan system failure. We describe an otherwise asymptomatic heart transplant recipient who had neurologic complaints that could be specifically attributed to PML, demonstrate the pertinent pathologic findings, and review the PML literature germane to heart transplantation. PML may become more prevalent as the population of heart transplant recipients increases. PMID- 1756155 TI - Role of routine endomyocardial biopsy to monitor late rejection after heart transplantation. AB - Endomycardial biopsy remains the standard used to monitor rejection after heart transplantation. There is, however, no consensus as to how often surveillance endomyocardial biopsy should be carried out after heart transplantation. We have analyzed 131 patients undergoing orthotopic heart transplantation during the first 4 years of the transplant program at St. Vincent's Hospital. The majority of endomyocardial biopsies that showed acute rejection occurred in the first 3 months after transplantation; after 9 months only 2.5% of endomyocardial biopsies performed showed rejection. Of those patients with rejection, 47% had symptoms. Seven patients experienced late rejection and all made a good recovery with normal cardiac function. We conclude that the incidence of acute rejection decreases significantly more than 3 months after-transplantation; after 9 months only 2.5% of endomyocardial biopsies will show rejection. Of these, 47% will be associated with symptoms. On the basis of experience, we believe that in our own unit, endomyocardial biopsy more than 9 months after transplantation seems unwarranted unless clinically indicated. PMID- 1756154 TI - Reduced incidence of severe infection after heart transplantation with low intensity immunosuppression. AB - Despite advances in immunosuppressive therapy and prolonged graft and patient survival, infection after heart transplantation remains problematic. From January 1987 through June 1989, 104 heart transplantations were performed in 100 patients. Immunosuppression induction was by antilymphocyte globulin for 7 days, with oral cyclosporine introduced on stabilization of kidney function (day 3). Steroid therapy was rapidly tapered, and azathioprine was added only in cases of positive donor crossmatch or steroid-resistant rejection. No reverse isolation was used. Twenty-two deaths occurred, one from sepsis. Actuarial survival at 6 months, at 1 year, and at 2 years was 85% +/- 4%, 81% +/- 3%, and 75% +/- 4%, respectively. Fifty-four patients had 81 infections, of which 21 were bacterial; 83% of these episodes were treated. Sixty infections were opportunistic (85% viral), and only 23% necessitated treatment. Actuarial infection-free rates (all types necessitating treatment) at 1 month, at 6 months, and at 2 years were 83% +/- 4%, 75% +/- 5%, and 75% +/- 5%, respectively. Of the 100 transplant recipients, 66% were treated with azathioprine; 47 patients (69%) had an infection, whereas only seven (19%) of the patients not receiving azathioprine became infected (p less than 0.00001). Rejection was noted in 66% of patients, with a median time to the first episode of 4 weeks. A low-intensity immunosuppressive regimen has resulted in fewer serious infections, with acceptable graft loss from rejection. Increased infection surveillance is required for the first 30 days postoperatively and after treatment of rejection episodes. PMID- 1756156 TI - Comparison of rejection in the atrioventricular node and bundles with the working myocardium in transplanted hearts. AB - At present the monitoring of heart transplant patients for rejection is done by endomyocardial biopsy. It has been proposed that ECG assessments of conduction delay may provide a noninvasive means of detecting rejection. To determine whether rejection in the atrioventricular node and conduction bundles reflects rejection in the working myocardium, we studied 21 transplanted hearts from 21 cardiac allograft recipients. Twenty of the hearts were obtained at autopsy, and one was obtained from a patient who underwent a second transplant procedure. The atrioventricular conduction tissues, the ventricular and atrial free walls, and the interventricular and interatrial septa from these hearts were examined for histologic evidence of rejection. Of the 21 hearts, 17 showed histologic changes of acute allograft rejection. Of the 17, rejection involved the conducting system and the myocardium equally in 11. In 6 of the 17 hearts, rejection involved the working myocardium more severely than it did the conducting system. Of interest, nonrejection pathologic changes were also noted in the conducting systems of several hearts. Severe accelerated arteriosclerosis was found in the artery to the atrioventricular node in one case, and lesser degrees of accelerated arteriosclerosis in this artery were found in two additional cases. In one case, lymphoid infiltrates, consistent with posttransplant lymphoproliferative disorder, were noted in the vicinity of the atrioventricular node, and several hearts demonstrated operative trauma or ischemic changes that appeared to involve the conducting system. These results suggest that although there may be a morphologic basis for using electrophysiologic changes in the conducting system to monitor heart allograft recipients for rejection, caution should be exercised in interpreting these changes. PMID- 1756157 TI - Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation. AB - Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection. PMID- 1756158 TI - Sudden death caused by bradycardia and asystole in a heart transplant patient with coronary arteriopathy. AB - The mechanism of death as a result of allograft ischemic heart disease is not well characterized. Ventricular tachycardia and fibrillation may not be the terminal events they often are in the general population. We report observations in a 41-year-old man with cardiac allograft arteriopathy who died suddenly while wearing an ambulatory monitor. The lethal rhythm was a progressive bradycardia terminating in asystole. Autopsy revealed epicardial and small vessel intramyocardial, coronary arteriopathy, and only mild allograft rejection. It is our belief that ischemia caused the bradycardic sudden death. We would like to hypothesize that prophylactic permanent pacemaker implantation may prevent bradycardic sudden death and improve survival in heart transplant patients with coronary disease. PMID- 1756159 TI - "Quilty effect" in heart transplantation: is it related to acute rejection? AB - "Quilty effect" is a lymphocytic infiltrate bulging in the endocardium of cardiac allografts with or without affectation of myocardium. It has been related with cyclosporine treatment. We have reviewed the morphology of 527 endomyocardial biopsy specimens from 46 transplant patients to study the significance and relation of Quilty effect with acute rejection. Paraffin immunoperoxidase studies were performed in 56 cases with Quilty effect or acute rejection. We graded acute myocardial rejection into four degrees according to the Hannover classification. A total of 126 biopsy specimens (24%) showed Quilty effect. Fifty-nine specimens (46.8%) showed different degrees of acute rejection in addition to Quilty effect. If we consider specimens with acute rejection grade greater than or equal to II, which require treatment, the frequency of the association of Quilty effect and acute rejection is statistically significant (p less than 0.01). In cases of acute rejection, the percentage of cases with Quilty effect was higher in cases with the highest degrees of acute rejection. The response of acute rejection to antirejection treatment was similar in all cases with or without Quilty effect. Immunohistochemical study showed a predominance of T lymphocytes in both Quilty effect and in the myocardium of acute rejection. We conclude that Quilty effect is a manifestation of acute rejection, modified by many factors, such as cyclosporine treatment. The finding of isolated Quilty effect may signal the prompt development of an acute rejection episode. PMID- 1756160 TI - The lack of predictive value of preoperative psychologic distress for postoperative medical outcome in heart transplant recipients. AB - This follow-up study of 58 heart recipients an average of 2 years after transplantation did not show that the Symptom Checklist 90R, a self-report measure of psychologic distress, predicted medical outcome. Mortality and medical morbidity (graft rejection and infection rate) were the outcome variables used. The findings tend to argue against the validity of some aspects of the psychiatric screening of transplant candidates if prediction of patients' ultimate risk of mortality or medical morbidity is the validation standard. PMID- 1756161 TI - Psychosocial evaluation of heart transplant candidates: an international survey of process, criteria, and outcomes. AB - Heart transplant programs were surveyed regarding psychosocial evaluation process, criteria, and outcomes. There was considerable disagreement among programs when a patient is rejected on psychosocial grounds with regard to the use of second opinions and how often patients are informed of the reasons. Wide discrepancies in criteria used and rates of patients refused on psychosocial grounds were discovered. More than 70% of all programs excluded patients for transplantation on the grounds of dementia, active schizophrenia, current suicidal ideation, history of multiple suicide attempts, severe mental retardation, current heavy alcohol use, and current use of addictive drugs. Lack of consensus was found for some exclusion criteria (cigarette smoking, obesity, noncompliance, recent alcohol or drug abuse, criminality, personality disorder, mild mental retardation, controlled schizophrenia, and affective disorder). The proportion of patients rejected for transplantation on psychosocial grounds ranged from 0% to 37%, with an average rate of 5.6% in the United States and 2.5% in non-U.S. programs. This survey thus supports the need for research on the validity and reliability of psychosocial selection criteria. PMID- 1756162 TI - Significance of bronchial mucosal blood flow for the monitoring of acute rejection in lung transplantation. AB - Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs. PMID- 1756163 TI - New diagnostic method for pulmonary allograft rejection by measurement of bronchial mucosal blood flow. AB - We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756164 TI - A comparison of UW cold storage solution and St. Thomas' solution II: a 31P NMR and functional study of isolated porcine hearts. AB - Although University of Wisconsin cold storage solution provides excellent preservation for the pancreas, the kidney, and the liver after extended cold ischemic storage, its ability to preserve the heart for extended cold storage periods is not yet proved. This study was carried out to evaluate the effect of University of Wisconsin solution on heart preservation and to compare it to modified St. Thomas' solution II with respect to the capacity to preserve high energy phosphates and contractile function in pig hearts. Hearts were arrested with either University of Wisconsin cold storage solution or St. Thomas' solution II (10 ml/kg) and kept ischemic at 12 degrees C or 4 degrees C for 8 hours. Functional recovery after the preservation period was assessed by means of ventricular function curves of the isovolumically contracting Langendorff model perfused with modified Krebs-Henseleit solution. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to monitor high-energy phosphates and intracellular pH during preservation and reperfusion. At 12 degrees C, hearts arrested and preserved with University of Wisconsin solution showed a rapid decrease in phosphocreatine and adenosine triphosphate. With St. Thomas' solution, phosphocreatine and adenosine triphosphate decreased slowly. Functional recovery was poorer with University of Wisconsin solution than with St. Thomas' solution. Hearts preserved at 4 degrees C with either solution showed no significant differences in high-energy phosphate content and functional recovery. Rigorous control of the low temperature (4 degrees C) is necessary when University of Wisconsin solution is used for heart preservation. PMID- 1756165 TI - Extracellular flush solution that contains blood, mannitol, albumin, and prostacyclin protects rat lungs from six hours of ischemia. AB - We have used an isolated rat lung model to compare the quality of preservation of different flush techniques with each other and with topical cooling alone. Lung injury was assessed by recording lung weights after reperfusion after 4 and 6 hours of ischemia. The flush solutions studied were intracellular (Collins Sacks), traditional extracellular, extracellular with low potassium plus dextran, and extracellular containing blood, mannitol, albumin, and prostacyclin (Wallwork's solution). Flushing with Wallwork's solution before both 4 and 6 hours of ischemia gave superior protection from lung edema after reperfusion over all the other methods. PMID- 1756166 TI - A new concept of long-term donor heart preservation: nucleoside transport inhibition. AB - Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756167 TI - Donor organ preservation fluids differ in their effect on endothelial cell function. AB - Successful organ transplantation depends on adequate preservation of cellular function. We tested the effect of four commonly used donor organ preservation fluids on the ability of cultured bovine pulmonary artery endothelial cells to release endothelium-derived relaxing factor (EDRF). Columns of endothelial cells grown on microcarrier beads were exposed to either University of Wisconsin (Belzer's) solution, Marshall's preservation fluid, Euro-Collins solution, or a blood-based preservation fluid at 4 degrees C for 6 hours, and then to Krebs Henseleit buffer at 37 degrees C for 1 hour. They were then stimulated with boluses of bradykinin, and the EDRF released was detected by bioassay. The release of EDRF from endothelial cells previously exposed to a preservation fluid was compared with the release of EDRF from control columns of cells perfused throughout at 37 degrees C with Krebs-Henseleit buffer. Previous exposure to any of the three non-blood-based preservation fluids did not attenuate bradykinin stimulated EDRF release. By contrast, previous perfusion with the blood-based solution completely inhibited EDRF release (p less than 0.01, ANOVA), an effect attributable to the acidity of the solution. Donor organ preservation fluids differ in their effect on endothelial cell function, and this has important implications for lung and for other organ transplantation. PMID- 1756168 TI - The nucleotide sequence of the Escherichia coli crp divergent RNA and an overlapping ORF. AB - The nucleotide sequence specifying the crp divergent RNA of Escherichia coli was determined. An open reading frame (ORF) is located at +135 to +536 relative to the initiation site of the divergent RNA. Potential factor independent transcription terminators were found at +257 to +294 and +544 to +576. These putative termination sites may account for the two RNAs of approximately 300 and 550 nucleotides previously identified as originating from the crp divergent promoter. PMID- 1756169 TI - A bacterial homolog to HPRT. AB - The deduced 182 amino acid sequence of an open reading frame in the photosynthetic bacterium Rhodobacter capsulatus shows significant similarity to the hypoxanthine-guanine phosphoribosyltransferases of other organisms. This similarity includes conserved amino acid residues involved in Lesch-Nyhan syndrome. PMID- 1756170 TI - Cloning and sequence analysis of hydrogenase regulatory genes (hydHG) from Salmonella typhimurium. AB - The nucleotide sequence of the hydHG operon, comprised of chromosomal genes that regulate labile hydrogenase activity in Salmonella typhimurium, was compared with the reported hydHG sequence of Escherichia coli. Nucleotide sequence analysis of a 4.8 kb EcoRI fragment of Salmonella chromosomal DNA revealed that one of the open reading frames (ORF) encoded a protein of 441 amino acid residues. This large ORF was identified on a 2.7 kb Eco RI/HindIII fragment and coded for the complete hydG gene. The carboxy-terminus (626 bp) of the hydH gene also was present immediately upstream of hydG. Expression of the Salmonella hydG gene in a T7 promoter/polymerase system revealed the presence of a unique 45 kDa protein band. The incomplete hydH gene was not expressed. It is proposed that the labile hydrogenase activity in S. typhimurium may be regulated by the multiple component system. PMID- 1756171 TI - Lipoamide dehydrogenase of Staphylococcus aureus: nucleotide sequence and sequence analysis. AB - A complex of four proteins was previously isolated from Staphylococcus aureus. The complex had a strong interaction with membrane bound ribosomes, which suggested that it may be involved in protein secretion. However, the complex was identified as pyruvate dehydrogenase (PDH), which disproved the direct role of the complex in protein secretion. Here we report the nucleotide sequence of the last gene of the S. aureus pyruvate dehydrogenase operon, pdhD, which encodes lipoamide dehydrogenase (LPD). The pdhD gene encodes a protein of 468 amino acids, with a molecular mass of 49.5 kDa. The protein is closely related to other lipoamide dehydrogenases from bacteria and eukaryotes. The possible role of membrane bound lipoamide dehydrogenase is briefly discussed. PMID- 1756172 TI - The nucleotide and deduced amino acid sequence of the cationic 19 kDa outer membrane protein OmpH of Yersinia pseudotuberculosis. AB - The OmpH proteins of enteric bacteria are recently described, small (16 kDa), cationic outer membrane proteins. Because a Yersinia pseudotuberculosis cell envelope protein of this size has been found to cross-react serologically with the human histocompatibility antigen HLA-B27 (B*2701), the sequence of Y. pseudotuberculosis OmpH was determined by sequencing the gene region which encodes mature OmpH. A protein consisting of 143 amino acid residues was found. It was 96% homologous with the OmpH of Y. enterocolitica and 62% homologous with that of Escherichia coli. Two separate OmpH regions had sequence similarity with B*2701; they were identical in both Yersinia species. PMID- 1756174 TI - Murine cyclophilin-S1: a variant peptidyl-prolyl isomerase with a putative signal sequence expressed in differentiating F9 cells. AB - Fractionation of differentiating murine teratocarcinoma F9 cells and extraction of the nuclear/microsomal pellets with ethidium bromide led to the purification and microsequencing of the protein mCyP-S1, a novel cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase (PPIase). mCyP-S1 is a new member of the cyclophilin class of proteins. Cloning and sequencing of the mCyP-S1 cDNA revealed extended coding capacity for a putative N-terminal signal sequence, suggesting processing of mCyP-S1 during intracellular translocation across the membrane of the endoplasmic reticulum. mCyP-S1 is abundantly expressed in a variety of mouse organ tissues and its mRNA levels increase during F9 cell differentiation. Specific subcellular localization of PPIases is postulated to contribute to functional specificities of this class of enzymes. PMID- 1756173 TI - Molecular cloning and sequence analysis of the mouse kallikrein-binding protein gene. AB - A genomic clone (MKBP-10) encoding the mouse kallikrein-binding protein (MKBP) was isolated from a mouse genomic DNA library by screening with a rat kallikrein binding protein (RKBP) cDNA probe. The total sequenced region of the MKBP gene spans 8615 base pairs. The exon and intron locations of the RKBP gene were identified by similarity with the RKBP gene. The MKBP gene encodes a prepeptide of 417 amino acid residues which exhibits 71% homology with RKBP. A TATA box sequence was located in the 5' flanking region of the MKBP gene by similarity with the consensus sequence TATAAAA. PMID- 1756175 TI - Cloning and sequence analysis of membrane-bound alkaline phosphatase cDNA of the silkworm, Bombyx mori. AB - The nucleotide sequence (1974 bp) of cDNA coding for membrane-bound alkaline phosphatases (m-ALP) of Bombyx mori was isolated. The cDNA clone contained an open reading frame encoding a polypeptide (547 amino acids), which contains a hydrophobic signal peptide of 36 amino acids and the mature protein of 511 amino acids (Mr = 56,163). We found a highly hydrophobic domain presumed to be a membrane anchoring region at the C-terminus. Comparing analysis between Bombyx m ALP and mammalian and Escherichia coli ALPs suggested an evolutionary relationship of sharing a common ancestral gene. PMID- 1756176 TI - Cloning and sequencing of the casein kinase 2 alpha subunit from Zea mays. AB - The nucleotide sequence of the cDNA coding for the alpha subunit of casein kinase 2 of Zea mays has been determined. The cDNA clone contains an open reading frame of 996 nucleotides encoding a polypeptide comprising 332 amino acids. The primary amino acid sequence exhibits 75% identity to the alpha subunit and 71% identity to the alpha' subunit of human casein kinase 2. PMID- 1756177 TI - The amyloid beta protein precursor or proteinase nexin II from mouse is closer related to its human homolog than previously reported. AB - The cDNA sequence for amyloid precursor protein and the two alternatively spliced forms were determined. Seven nucleotide differences resulting in six amino acid differences compared to the previously published mouse sequence were found. Moreover, the 3' non-coding end was completely different. Part of these findings were confirmed in three different mouse strains. The resulting mouse cDNA resembles the human APP more closely than originally reported. PMID- 1756178 TI - Reduced levels of alpha 1 (I) collagen mRNA in cells immortalized by mutant p53 or transformed by ras. AB - Genes whose expression patterns are altered in a cell line immortalized by mutant p53 were isolated by differential screening of a cDNA library. Levels of alpha 1 (I) collagen mRNA were reduced in the majority of immortalized cell lines which greatly overproduced the transfected mutant p53. This may reflect a co-selection during the establishment of the cell lines, rather than a direct effect of p53 on alpha 1 (I) collagen gene expression. On the other hand, a more direct relationship could be demonstrated between the expression of activated ras and a reduction in alpha 1 (I) collagen mRNA. Such reduction could partially account for the effects of ras on cell shape and cell proliferation. PMID- 1756179 TI - Histones and DNA methylation in mammalian chromatin. II. Presence of non inhibitory tightly-bound histones. AB - After removal, by high-salt extraction, of the loosely-bound components present in human placenta chromatin, tightly-bound cationic proteins could be solubilized, by acid extraction, from the 'stripped' chromatin, as well as from the 'stripped' loops or from the 'digested matrix'. These acid-soluble tightly bound proteins are, in terms of apparent molecular mass and immunoreactivity, quite similar to the 'typical', loosely-bound histones, and, similarly to their 'loosely-bound' counterparts, they can be subdivided in distinct H1-, H2A-, H2B-, H3- and H4-like components, the 'digested matrix' being however characterized by the absence of tightly-bound H1. These tightly-bound histones, at variance from the 'typical' ones, readily find a right-handed helical conformation upon renaturation by progressive dialyses. The H1 components strongly differ also in their effects on enzymic DNA methylation: while 'typical' H1 has a strong inhibitory effect, its tightly-bound counterpart exerts a slight but definite stimulation. PMID- 1756180 TI - Histone-DNA contacts in the 167 bp 2-turn core particle. AB - The histone-DNA contacts in the 167 bp 2-turn core particle have been compared with those in the 146 bp 1.75-turn core particle by the methodology developed by Mirzabekov and his colleagues. The contacts in the 167 bp 2-turn core particle retain the essential features of those in the 146 bp 1.75-turn core particle but contacts for histones H3 and H2A were found in the 10 bp extension that discriminates the two particles. In addition the contact for histone H2A near the dyad axis was far more pronounced in the case of the 146 bp core particle. PMID- 1756181 TI - Thermal stability of turnip yellow mosaic virus RNA: effect of pH and multivalent cations on RNA deaggregation and degradation. AB - Light scattering studies of RNA isolated from turnip yellow mosaic virus (TYMV) revealed a molar mass of 1.9.10(6) g mol-1, which is close to the value of 2.0.10(6) g mol-1 published for intact genomic TYMV RNA (2M RNA). However, gel electrophoresis under denaturing conditions demonstrated that only 30-40% of this native RNA was 2M RNA. Sucrose gradient centrifugation revealed the occurrence of a series of smaller RNA size classes, the mass ratios of which were greatly influenced by the pH of the solution and the presence of EDTA. These results suggest that native TYMV RNA preparations originally contain a mixture of intact RNA particles and of aggregates of RNA fragments with the same molar mass of about 2.10(6) g mol-1, and that the size classes are intermediates in the deaggregation process of the degraded genomic TYMV RNA. The native RNA displayed pH-dependent deaggregation and degradation. The degradation process of 2M RNA followed (pseudo) first-order kinetics. Lower degradation rates were observed for RNA depleted of divalent cations and polyamines. For depleted 2M RNA an enthalpy of activation of about 100 kJ mol-1 and an almost zero entropy of activation was calculated. Similar values were also found for depleted E. coli ribosomal RNAs and depleted MS2 RNA, demonstrating that all RNAs are equally vulnerable to degradation. In the presence of multivalent cations the activation enthalpy for 2M TYMV RNA degradation increased to 150 kJ mol-1 and the entropy of activation to 150 J K-1 mol-1, indicative for a different degradation mechanism. PMID- 1756182 TI - The organization and expression of the human L7a ribosomal protein gene. AB - The genomic structure and sequence of the human ribosomal protein L7a (rpL7a) and its transcriptional start sites have been determined. The gene contains eight exons and seven introns spread over 3179 bp. The human rpL7a gene is similar to other mammalian ribosomal protein genes in containing a short first exon, a short 5' untranslated leader and its transcriptional start sites at C residues embedded in a polypyrimidine tract. The 25 bp polypyrimidine tract containing the two human rpL7a start sites is the longest polypyrimide tract so far observed for a mammalian ribosomal protein gene. PMID- 1756183 TI - Cloning of cDNA encoding rat TCP-1. AB - We have isolated and sequenced a cDNA encoding a rat homolog of the mouse t complex polypeptide 1 (TCP-1). Its deduced gene product is a polypeptide of 556 amino acids, with a predicted Mr of 60,341. The similarity between mouse Tcp-1 and the rat homolog is about 94.0% at the nucleotide level and 97.1% at the amino acid level showing the evolutionary conservation of this protein. The similarity of the amino acid sequence of the rat TCP-1 is not significantly biased to any of those from wild (TCP-1B) or from t-haplotype mice (TCP-1A). From a comparison of deduced amino acid sequences of eukaryotic TCP-1 proteins, we found highly conserved domains. Southern blot analysis revealed that there are at least two similar sequences to Tcp-1 in the rat, one is a structural gene and the other seems to be a processed pseudogene. PMID- 1756184 TI - Purification to homogeneity of alpha (III) collagen chain from human placenta by preparative electrophoresis. AB - A multiple electrophoretic method suitable for purification of type III collagen from a mixture of various collagen types is described. The technique is based on preparative electrophoresis in acid media and successive electroelution of the collagen fractions. By sodium dodecyl sulfate-polyacrylamide electrophoresis and immunoblotting, the collagen composition of the electroeluted fractions was characterized as a mixture of alpha (III), beta (III) and gamma (III) without any other visible contaminants. This technique enabled us to obtain large quantities of type III collagen from partial pepsin digests of human placenta suitable for further processing. PMID- 1756185 TI - Detection of beta-glucosidase activity on sodium dodecyl sulphate-polyacrylamide gels. AB - Maize beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was incubated in the presence of SDS concentrations varying from 0.025 to 3.2% at two different pHs (5 and 8), electrophoresed through 10% SDS-polyacrylamide gels, and stained for activity. The zymogram patterns of SDS-treated samples were similar to those of untreated (control) samples. The same samples were also analyzed by native PAGE and IEF, yielding similar patterns for controls and for SDS-treated samples. However, zymogram patterns were severely distorted on IEF gels when SDS concentration of the sample medium was at or above 1.6%. These results suggest that the beta-glucosidase monomer (a 60 kD polypeptide) is either catalytically active or it re-forms dimers upon the removal of SDS during equilibration washes, since the in vivo form of the functional enzyme is thought to be a dimer. The activity of maize beta-glucosidase on SDS-gels after SDS-PAGE does not seem to be limited to this enzyme alone, because beta-glucosidases from other sources (e.g., almond, Trichoderma, and Penicillium) were also active on SDS-gels. Enzyme activity in the presence of SDS or after SDS treatment may be more common than one would expect on the basis of the conventional biochemical dictum that ionic detergents denature and inactivate enzymes. Enzyme activity in the presence of SDS and development of zymograms on SDS-gels offer new approaches to studies of enzyme structure and activity. PMID- 1756186 TI - A method for extraction and 2-D gel electrophoresis of plant proteins with selective isoelectric points. AB - A procedure for extracting and separating plant proteins by isoelectric point and 2-dimensional gel electrophoresis (2-DGE) is presented. Resolution of basic proteins using nonequilibrium pH gradient electrophoresis (NEPHGE) increased when run without the presence of acidic proteins. Isoelectric focusing without basic proteins favored the migration of the acidic and the more neutrally charged proteins into tube gels. Without the basic groups, negatively charged proteins could be focused for 20 h and longer without consideration of cathodic drift effects. The procedure facilitates gel analysis by simplifying the protein pattern on second dimension gels. Another advantage is that greater relative amounts of any class of proteins can be electrophoresed in the first dimension gels. PMID- 1756187 TI - Histo-electrophoretic analysis of the microheterogeneity and region-specificity of isozymes. AB - An optimal and practical method for high resolution separation and visualization of soluble and membrane-binding isoenzymes is described. By use of this method, non-specific esterase, lactate dehydrogenase and acid phosphatase from different tissues of mice can be separated into more than 50, 30 and 20 components, respectively. Cholinesterase, glucose-6-phosphate dehydrogenase, acid phosphatase, succinate dehydrogenase, lactate dehydrogenase and non-specific esterase isolated from the lumbar spinal cord of chick embryos at different ages can be separated into about 15, 12, 9, 6, 14 and 20 components, respectively. In addition, an attempt has been made to evaluate quantitatively by densitometry differences in enzyme activity among different regions of the same tissue (e.g. spinal cord). The findings revealed that there are differences in isoenzyme components between the dorsal and ventral regions of the spinal cord. Collectively, the combination of direct tissue isoelectric focusing and fast enzyme visualization reveals a greater number of isoenzyme components than can be demonstrated by other means. This method is an extremely useful procedure for understanding and analyzing the nature and topographic localization of isoenzyme components. PMID- 1756188 TI - Electrohydrodynamic effects in continuous flow electrophoresis. AB - We demonstrate experimentally and theoretically the importance of electrohydrodynamic (EHD) flows in continuous-flow electrophoresis (CFE) separations. These flows are associated with variations in the conductivity or dielectric constant, and are quadratic in the field strength. They appear to be the main cause of extraneous and undesired flows in CFE which have degraded separation performance and have until now not been explained. We discuss the importance of EHD flows relative to other effects. We also describe possible techniques for reducing the associated degradation of CFE separations. PMID- 1756189 TI - Nuclear protein phosphorylation in rat cerebral cells following acute exposure to ethanol. AB - The sequelae of acute ethanol toxicity encompass a broad spectrum of metabolic and cellular derangements, including the induction of stress proteins in cells exposed to high levels of ethanol. In this investigation, the effects of ethanol exposure on nuclear protein synthesis and phosphorylation were compared by two dimensional gel electrophoresis in glial-enriched cultures, adult rat cerebrum and regenerated liver. Cellular exposure to ethanol was at clinically relevant levels and tissue was analyzed at 1 h and 48 h after exposure. Cell nuclei were stained with propidium iodide, a DNA specific fluorochrome and flow cytometrically sorted to obtain cell cycle phase populations of nuclei for analysis. Ethanol treatment of intact rats and glial-enriched cultures induced phosphorylation of specific nuclear proteins, which were detected by two dimensional electrophoresis and autoradiography. The autoradiographs of [32P]phosphate and [3H]leucine labeled proteins from glial-enriched cultures and from the G0/G1 phase of the regenerating liver tissue exhibited intense labeling indicative of active protein synthesis and phosphorylation. In contrast, the autoradiographs of proteins from adult rat cerebra showed substantial phosphorylation, but weak protein synthesis. Ethanol treatment was associated with phosphorylation of a 50,000 Mr protein in G0/G1 phase cells of the cultures and in predominantly G0 cells of the adult rat cerebra. A protein with similar characteristics was not found in ethanol exposed regenerating rat liver tissue and has not been observed in other 'heat shock' or 'stress' protein systems which we have previously studied. PMID- 1756190 TI - Granulocyte-macrophage colony-stimulating factor and interleukin-3 in combination: a potent and consistent myelodysplastic syndrome bone marrow stimulant in vitro. AB - In an effort to overcome bone marrow failure in myelodysplastic syndrome (MDS), we have investigated recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in phase I-II clinical trials. Although these agents partially increased peripheral blood granulocyte counts, their effect on other hematopoietic lineages was generally sporadic. Since in vitro analysis and in vivo studies in primates indicate that GM-CSF and IL-3 synergistically enhance hematopoietic stem cell proliferation, we evaluated their combined effect on marrow progenitors obtained from ten MDS patients. When used singly, each growth factor stimulated replication of granulocyte-macrophage (CFU GM) and erythroid (BFU-E) colony-forming cells in a dose-dependent fashion. When colony-stimulating activity was compared at concentrations that maximally amplified individual MDS patients' colony numbers, IL-3 was a more potent stimulant in some patients and GM-CSF in others. When used in combination, IL-3 plus GM-CSF was more effective than each growth factor by itself in five of six patients. Our data indicate that the MDS hematopoietic progenitor stimulatory effect of these growth factors varies from patient to patient. However, the combination of GM-CSF and IL-3 appears to be more potent than the individual molecules in the majority of patients. PMID- 1756191 TI - In vitro evaluation of a high-efficiency leukocyte adherence filter. AB - In view of the currently available data, prevention of alloimmunization requires filters with higher efficiency to achieve a reduction in the number of leukocytes below 10 million per transfusion. Two versions (Pall PL-100 and PL-50) of the new generation leukocyte-depletion filters were studied. Single donor (SDPC)- and pooled multiple donor (MDPC) platelets were run in parallel. At a flow rate of 10 ml/min, the PL-100 filter was shown to effectively reduce the number of residual leukocytes to far below the critical immunogenic threshold of 10 million in all SDPC units and in 77% of MDPC units. Apheresis platelets appear not only to be better depleted than pooled multiple donor platelets, but also to have a better post-filtration platelet recovery (96% versus 84%). The efficiency of the smaller version of the filter (Pall-50) was higher than that of the Pall-100 filter for both single and pooled multiple donor platelet concentrates (PC). Leukocytes were absent in more than 92% of units in both types of concentrates. The maximal number of detected leukocytes was 2.2 million in a pool of 6 units. The outcome of filtration of 5-day-old pooled platelets was less favorable than filtration of 1- or 2-day-old pooled platelets, indicating that filtration soon after preparation is preferred to filtration after storage. Post-filtration platelet integrity, activation state, function, and morphology were all well preserved in both single and multiple PCs. PMID- 1756192 TI - Confirmation and improvement of Sokal's prognostic classification of Ph+ chronic myeloid leukemia: the value of early evaluation of the course of the disease. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. AB - A simple prognostic classification of Ph+ chronic myeloid leukemia (CML) was proposed in 1984 by an international study Group and is now widely used for clinical purposes. That study was retrospective, and was based on disease features at diagnosis. To test prospectively and to check the value of the classification, and to investigate if additional information on the early course of leukemia can help in refining the prognosis, 505 Ph+, nonblastic and nontransplanted patients first registered between 1984 and 1986 were followed up to June 1990. It was found that the prognostic formulation predicted survival in that series exactly the same way as in the original series (median survival: greater than 60 months for low-risk patients, 46 months for intermediate-risk patients, and 32 months for high-risk ones). It was also found that several objective or subjective assessments of disease course during the first 8 months after diagnosis were significantly related to survival length within any risk group. This study provides full confirmation of Sokal's international prognostic classification, and shows that the definition of prognosis can be improved some months after diagnosis by taking into account the course of the disease and the response to therapy. These conclusions apply to patients receiving conventional treatment. The course of Ph+ chronic myeloid leukemia (CML) is rigidly programmed to progress to an acute phase, which is called blastic metamorphosis (BM) and which can develop either suddenly (blastic crisis) or by a slow progression (accelerated phase). In all recent series, 2-year survival ranged between 65% and 80%, median survival was slightly shorter than 4 years, and the proportion of patients who were still alive after 10 years was less than 10%. However, a number of prognostic variables were identified and a prognostic formulation that was elaborated by an international study was shown to provide a reliable estimate of survival length and is currently used for that purpose. The value of that formulation, and the formulation itself, require periodical controls and revisions. For that purpose, the Italian Cooperative Study Group on CML registered and followed up all CML patients who were first seen between 1984 and 1986. A very preliminary analysis of that cohort of patients has already been performed, but it was limited to the first 2 years after diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756193 TI - Impaired in vitro growth of peripheral blood hematopoietic progenitor cells in HIV-infected patients: evidence of an inhibitory effect of autologous T lymphocytes. AB - The in vitro growth of both circulating granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells was assessed in 29 individuals infected with the human immunodeficiency virus (HIV) at different stages of infection. The effects of autologous T lymphocytes, adherent cells, and serum on the in vitro growth of hematopoietic progenitor cells were also investigated. Compared with normal controls, baseline growth was significantly reduced for both CFU-GM and BFU-E in HIV-infected patients, independent of the clinical stage of the disease. In HIV-infected subjects depletion of autologous T cells was associated with a significant increase of progenitor cell growth. Similar results were observed after selective depletion of CD8+ T cells, while readdition of T cells to T depleted mononuclear cells reduced the number of CFU-GM. A dose-dependent colony inhibitory activity was found in conditioned medium of T cells from HIV-infected subjects. Neither autologous adherent cells nor serum from either HIV+ or HIV- subjects had any significant effect on the in vitro growth of CFU-GM. These results indicate that the in vitro growth of circulating hematopoietic progenitor cells is impaired even in the early stages of HIV infection, and that autologous T cells exert an inhibitory effect on the in vitro growth of progenitor cells, possibly via soluble mediator(s). PMID- 1756194 TI - Successful short-term treatment with granulocyte-macrophage colony-stimulating factor of neutropenia due to cytotoxic chemotherapy of chronic lymphocytic leukemia. PMID- 1756195 TI - Incidence of hypercortisolism and dexamethasone resistance increases with age among wild baboons. AB - While many features of the adrenocortical axis are unchanged with age in humans, there is a pattern of senescent hypercortisolism. This occurs basally, following threshold doses of dexamethasone, and in synergy with depression or Alzheimer's disease. An understanding of neuroendocrine aging is important, for both its gerontological implications, and determination of normative values for comparison with neuropsychiatric states. We have investigated whether aging is associated with hypercortisolism in a population of wild primates. The subjects were 108 yellow baboons (Papio cynocephalus) that have been under long-term study of Amboseli National Park in Kenya. Animals were anesthetized by blowgun under similar circumstances that allow for determination of basal cortisol concentrations. Sixty minutes later, 5.0 mg dexamethasone was administered to each animal, and cortisol determinations were made on serum collected immediately before administration and 6 hr later. Basal cortisol concentrations rose with age (p less than 0.028; r = 0.23). This occurred in a nonprogressive manner, in that there were no differences in concentrations among the youngest three quartiles of animals, whereas animals in the oldest quartile (older than approximately 16 years) had significantly higher values. In addition, there was a significant increase in postdexamethasone cortical concentrations with age (p less than 0.01; r = 0.31). This feature emerged progressively with age in both sexes. A number of possible artifactual causes of this senescent pattern could be eliminated, including medication confound, coincident disease, and body weight. These findings suggest that hypercortisolism and glucocorticoid feedback resistance might be general features of primate aging. PMID- 1756196 TI - Neuroendocrine responses to serotonergic agents in alcoholics. AB - Previous studies have suggested a possible deficit in serotonergic function in alcoholism. In order to further assess the serotonergic system in alcoholism, the plasma cortisol and prolactin (PRL) responses following 6-chloro-2-[1 piperazinyl]pyrazine (MK-212), a direct-acting serotonin2 (5-HT2)/5-HT1c receptor agonist, L-5-hydroxytryptophan (L-5-HTP), a precursor of 5-HT, and placebo were compared in male alcoholics and normal controls. The increase in plasma cortisol following L-5-HTP was significantly lower in the alcoholic subjects compared with the normal controls. The plasma PRL, but not the plasma cortisol response, following MK-212 was also significantly lower in the alcoholics. L-5-HTP had no significant effect on plasma PRL levels in either group. The basal plasma cortisol and PRL concentrations of the alcoholics and normal controls were not significantly different. These data are consistent with previous reports of a serotonergic abnormality in alcoholism. PMID- 1756197 TI - Childhood obsessive-compulsive disorder and cingulate epilepsy. AB - There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive compulsive symptomatology. Her scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms. PMID- 1756198 TI - Mismatch negativity: an index of a preattentive processing deficit in schizophrenia. PMID- 1756199 TI - Haloperidol and soluble interleukin-2 receptors. PMID- 1756200 TI - Annual meeting theme for 1992: developmental neurobiology and clinical course. PMID- 1756201 TI - Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients. AB - Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine beta synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned. PMID- 1756202 TI - Anxiogenic effects of m-CPP in patients with panic disorder: comparison to caffeine's anxiogenic effects. AB - The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind conditions. Both m-CPP and caffeine had significantly greater anxiogenic and panic-inducing effects than placebo, although caffeine produced nonsignificantly greater increases on all anxiety rating scales than m CPP. Both m-CPP and caffeine produced significant equivalent increases in plasma cortisol concentrations, but only m-CPP produced plasma prolactin increases. These findings provide further evidence implicating both the serotonergic and adenosinergic receptor systems in the neurobiology of panic disorder. PMID- 1756203 TI - Hormonal regulation of uterine secretion of prostaglandin F2 alpha during luteolysis in ruminants. AB - In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of prostaglandin F2 alpha (PGF2 alpha) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2 alpha secretion from the uterus. Uterine PGF2 alpha stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2 alpha from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2 alpha at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2 alpha observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2 alpha normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2 alpha occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2 alpha secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2 alpha. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2 alpha is secreted only at the appropriate time to induce luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756204 TI - Cell interactions with laminin and its proteolytic fragments during outgrowth of mouse primary trophoblast cells. AB - Mouse blastocysts in serum-free culture for 24-48 h become attachment-competent, adhere to fibronectin- or laminin-coated surfaces, and subsequently form trophoblast outgrowths. The blastocyst laminin receptor was characterized in outgrowth studies using modified laminin. Trophoblast cells interacted with the peptide portion of laminin, but not the oligosaccharide moiety since its adhesive activity was reduced by boiling or trypsin treatment, but not by treatments that removed or modified its carbohydrate. Laminin outgrowth-promoting activity was further localized within its structural domains by use of the well-characterized proteolytic fragments of laminin, E1-4, and E8, and a synthetic peptide, CDPGYIGSR. The E1-4 fragment of laminin did not promote embryo outgrowth. However, the E8 fragment, which contains a heparin-binding domain as well as sites recognized during cell adhesion and neurite outgrowth, vigorously promoted outgrowth in both the presence and absence of heparin, heparan sulfate, or heparinase. Consistent with these results, outgrowth on intact laminin was not inhibited by CDPGYIGSR, a sequence within the E1-4 fragment that is known to mediate the adhesion of some cell types. It is concluded from these results that early trophoblast cells adhere to peptide in the E8 domain of laminin using a mechanism that is independent of the one used for adhesion to fibronectin. PMID- 1756205 TI - Persistent sexual behavior in castrated, recombinant inbred mice. AB - In contrast to other male mice, many hybrid B6D2F1 males continue to mate after being castrated in adulthood. This persistent sexual behavior in the castrated hybrids presumably is based upon heterozygosity that might occur within individual loci or between different loci. Those possibilities were discriminated by studying BXD recombinant inbred mice. In BXD strains, individual loci are homozygous, but heterozygosity has arisen between separate loci. Males in two of six BXD strains persisted in copulating for 5 mo after being castrated. Thus, it is concluded that retention of masculine sexual behavior in castrated mice is a function of heterozygosity between loci. PMID- 1756206 TI - Synthesis and secretion of immunoreactive methionine-enkephalin from rabbit reproductive tissues in vivo and in vitro. AB - The expression of the proenkephalin gene has been demonstrated in the reproductive tissues of several animal species. The objectives of the experiments reported here were to (a) examine the presence of immunoreactive methionine enkephalin (ir-MENK) in rabbit ovary, oviduct, and uterus and in a rabbit endometrial cell line (HRE-H9), (b) characterize ir-MENK biochemically, (c) investigate the effect of eCG + hCG treatment on the synthesis and secretion of ir-MENK in vivo, and (d) study the effect of K+ depolarization on the secretion of ir-MENK from HRE-H9 cells. Uterine fluid was collected by flushing the uterine lumen with saline. Reproductive tissues and HRE-H9 cells were extracted with 0.1 N acetic acid. Both the uterine fluid and extracts of uterus, ovary, oviduct, and HRE-H9 cells exhibited inhibition curves parallel to that of authentic MENK in the MENK RIA system. Sephadex G-15 gel filtration profiles indicated that in the extracts of rabbit uterus and HRE-H9 cells, most ir-MENK co-eluted with standard MENK, with a minor portion eluting near the void volume (Vo). Reverse-phase-HPLC (RP-HPLC) profiles showed a major peak coinciding with standard MENK, plus a minor peak of highly hydrophilic ir-MENK. The effect of eCG + hCG treatment was studied by i.m. injection of eCG (150 IU), followed by i.v. injection of hCG (75 IU) 4 days later. Ir-MENK concentration in the uteri and ovaries was significantly (p less than 0.05) increased (9.06 +/- 1.89 and 2.05 +/- 0.32 ng/mg protein, respectively), compared to control levels (2.31 +/- 0.86 and 0.24 +/- 0.77).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756207 TI - Expression of perforin by natural killer cells within first trimester endometrium in humans. AB - The lymphocyte pore-forming protein (PFP)--perforin, also named cytolysin--is a potent mediator of cytotoxicity found in the granules of cytotoxic T lymphocytes and natural killer (NK) cells. Granulated metrial gland (GMG) cells found in the pregnant mouse uterus express perforin and are thought to be highly activated cytolytic lymphocytes related to NK cells. Their role in pregnancy is unknown. Human endometrial granulocytes (EGs) are phenotypically similar to murine GMG cells and, like them, express NK cell markers. However, up to now it was not known whether EGs also express perforin. By means of immunohistochemical analysis, using antisera specific for perforin and monoclonal antibodies to CD56 (NKH-1), CD2 (T11), CD3 (Leu-4), CD4 (Leu-3a), and CD8 (OKT-8), we demonstrated that perforin is present in EGs in the decidualized endometrial stroma and decidual tissue of first-trimester gestational endometrium. In fact, double immunohistochemical labeling demonstrated the co-expression of perforin and NKH 1. This population also expressed some T-cell surface antigens (Leu-4 and T11), but not Leu-3a or OKT-8. Chorionic villi, in contrast, lack perforin+ cells. The presence of a potent cytolytic mediator in NK-like cells in both murine and human pregnant uterus raises the issue of the function of such cells in pregnancy. PMID- 1756208 TI - Localization of pregnancy-specific beta 1-glycoprotein in the male reproductive tract of the rat by in situ hybridization. AB - Human pregnancy-specific beta 1-glycoprotein (PSG) is found in high concentrations in the serum of pregnant women, but also has been found in the serum of males and nonpregnant females. Northern slot-blot analysis has demonstrated the presence of PSG mRNA in a variety of tissues in the rat, with the highest levels being found in the testis. Therefore, we have investigated further the expression of PSG in the rat male reproductive tract using in situ hybridization. In testes from immature and adult rats, PSG mRNA was localized in Leydig and peritubular cells, and in the walls of the interstitial blood vessels. PSG transcripts were noted also in the tunica albuginea and in the stromal tissue of the caput and cauda epididymis, prostate, and seminal vesicle from adult rats. The function of PSG is unknown, but it has been speculated that PSG may have immunosuppressive properties or that it may serve as a paracrine regulator of growth and differentiation. It is possible, then, that PSG could contribute to the immunological privilege of the testis or that it plays a role in the cellular interactions which increasingly are being shown to be important in the regulation of male reproductive tract tissues. PMID- 1756209 TI - The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia. AB - Mice homozygous for a mutant allele (an/an) causing a lifelong macrocytic anemia (Hertwig's anemia) also demonstrate an inability to deliver their offspring, despite normal ovulation, conception, implantation, and fetal development. We investigated the roles of estrogen and relaxin in the etiology of the reproductive defect in the Hertwig's anemia mice. Immunoreactive relaxin levels were undetectable in the nonpregnant controls, whereas levels in both timed pregnant controls and timed-pregnant affected mice were significantly higher than in nonpregnant controls, but not significantly different from each other. Mean interpubic ligament length in the pregnant Hertwig's anemia mice was significantly greater than that in nonpregnant controls, but significantly less than that in the pregnant controls on Day 18 of pregnancy. Porcine relaxin was administered to nonpregnant affected and unaffected littermates and to nonpregnant controls. Whereas controls showed a significant response to porcine relaxin, neither the Hertwig's anemia mice nor their unaffected littermates responded to the porcine relaxin. Additional study was performed to determine estradiol effects in the affected and control animals utilizing detailed computerized morphometric analysis of uterine horns and cervices from immature, estradiol-injected controls and Hertwig's anemia mice. Results demonstrated a statistically significant trophic effect of estradiol upon uterine horn and cervical enlargement, as assessed by weight and volume, in controls. Only a slight, non-significant effect was seen in Hertwig's anemia mice. Additional histological effects of estradiol, including endometrial enfolding observed in controls, were not present in Hertwig's anemia mice. Lack of response to both estrogen and relaxin is responsible for the parturitional defect in Hertwig's anemia mice. PMID- 1756210 TI - Blocking of human sperm-zona interaction by monoclonal antibodies to a glycoprotein family (ZP4) of porcine zona pellucida. AB - To study zona pellucida antigens involved in human fertilization, five monoclonal antibodies (MAbs)--2A1, 2G3, 4A2, 4E12, and 5H4--were produced to a glycoprotein family (ZP4) isolated from heat-solubilized porcine zonae pellucidae. Each MAb reacted not only with solubilized porcine zona glycoproteins but also with the glycoproteins deglycosylated by trifluoromethanesulfonic acid treatment. They also reacted with intact zonae pellucidae of porcine and human oocytes. Three (4A2, 4E12, and 5H4) of the five MAbs showed a significant blocking effect on human sperm binding and penetration of human zonae pellucidae. The 5H4 MAb showed a strong reaction with ZP4 and ZP1 glycoprotein families of porcine zonae pellucidae, and four other MAbs reacted more strongly with ZP3 than with ZP4. The reactivity of 5H4 with porcine zona glycoproteins was destroyed by chymotrypsin digestion, but the antigen epitope was resistant to proteolysis by trypsin and endoproteinase Lys-C. A peptide fragment reactive to 5H4 was isolated by reverse phase HPLC from endoproteinase Lys-C-treated ZP4 glycoproteins, and its molecular mass was determined to be 7 kDa by SDS-PAGE. These results suggested that the antigen epitope corresponding to 5H4 is a good candidate for development of a contraceptive vaccine. PMID- 1756211 TI - In vitro-matured/in vitro-fertilized bovine oocytes can develop into morulae/blastocysts in chemically defined, protein-free culture media. AB - Development of bovine embryos derived from in vitro-matured/in vitro-fertilized (IVM/IVF) oocytes was examined in two culture media: hamster embryo culture medium (HECM), a relatively simple, chemically defined, protein-free medium containing 20 amino acids; and tissue culture medium (TCM)-199, a more complex medium designed for culture of somatic cells. The first experiment studied (1) effects of glucose and/or phosphate (Pi) using HECM and (2) the development of bovine IVM/IVF embryos in four different conditions: HECM, TCM-199, TCM-199 + 10% unheated bovine calf serum (BCS), and oviduct cell-conditioned TCM-199 + 10% BCS. After IVF, 45% of the inseminated oocytes developed to the morula/blastocyst stages (M&B) when cultured in HECM; blastocyst development was depressed in the presence of glucose and Pi when compared to Pi alone. When the four culture conditions were compared, there was no significant difference in M&B development (42-51% of inseminated oocytes). However, blastocyst development in TCM-199 supplemented with 10% BCS (29.7%) or with BCS + oviduct cell-conditioned medium (21.6%) was significantly greater than in nonsupplemented HECM (9.7%) or TCM-199 (13.8%). In the second experiment, the effects of serum supplementation and/or oviduct cell conditioning on HECM and TCM-199 were examined in a 2 x 2 x 2 factorial experiment. Oviduct cell conditioning of either HECM or TCM-199 without serum supplementation did not enhance bovine embryo development. Serum supplementation exhibited a biphasic effect, with inhibition at the first cleavage and stimulation of morula compaction and blastocyst formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756212 TI - Normal sequence of the gonadotropin-releasing hormone gene in patients with idiopathic hypogonadotropic hypogonadism. AB - Idiopathic hypogonadotropic hypogonadism (IHH) results from absent or greatly diminished secretion of GnRH. Defects in the GnRH gene have been identified in an animal model of IHH and have been hypothesized as a possible basis for GnRH deficiency in humans. In this study, we used the polymerase chain reaction to clone and sequence the coding regions, promoter, and 3' untranslated tract of the GnRH genes from both alleles of four unrelated patients with IHH. One of the patients studied is a member of a kindred in which X-linked inheritance has been excluded by father-to-son transmission of the disease. No DNA sequence mutations were found. We conclude that most cases of IHH in humans do not involve mutations in the GnRH gene and are presumably caused by mutations at one or more other genetic loci that are required for normal function of GnRH-producing neurons. PMID- 1756213 TI - Effect of sampling interval on serum concentrations of luteinizing hormone, follicle-stimulating hormone, and prolactin in prepubertal, ovariectomized, and cycling gilts. AB - Three experiments were conducted to determine the effect of sampling interval on serum concentrations of LH, FSH, and prolactin (PRL) in prepubertal, ovariectomized, and cycling gilts. In all experiments, blood samples were drawn at 2-min intervals for 4 h from indwelling jugular catheters. Mean serum hormone concentrations, mean number of peaks, and mean and maximum peak heights of LH, FSH, and PRL were calculated using values reflecting 2-, 6-, 10-, 20-, 30-, and 60-min sampling intervals. For LH, FSH, and PRL, mean serum concentrations can be obtained through blood samples drawn at hourly intervals. Since LH peaks are very distinct in pigs, the number of secretory peaks and mean peak height can be obtained via samples drawn at 20-min intervals. Since FSH and PRL peaks are less well defined, a more frequent sampling interval (10 min) is needed to determine number of peaks and mean peak height. To obtain the maximum peak height or the number of minutes for LH, FSH, or PRL to rise from its nadir to zenith, blood samples need to be drawn at 2-min intervals. Regardless of reproductive state, these data indicate that the sampling interval needed to characterize serum concentrations of LH, FSH, and PRL in the gilt is dependent upon the parameter in question. PMID- 1756214 TI - Regional cellular heterogeneity and DNA synthetic activity in rat ventral prostate during postnatal development. AB - Previous studies have provided evidence that the rat ventral prostate grows primarily, if not exclusively, at its distal tips. However, as yet there have been no analyses in which individual cells in defined regions of the prostatic ductal system have been resolved and quantified. Moreover, the possibility that the prostate might grow differently at different times of postnatal development has received little attention. Our objectives were to identify and quantify the proliferating epithelial and stromal cells in defined regions of the rat ventral prostate during its postnatal development. To this end, 3H-thymidine was administered in vivo to rats of ages 10-60 days. A dissection technique was then used by which the distal, intermediate, and proximal segments of the prostatic ductal system were physically isolated from each other without removing the stromal tissue. Longitudinal sections of these segments were examined for cellular composition and DNA synthetic activity. Regional heterogeneity with respect to cell composition and cell proliferation was seen. In rats of all ages, DNA synthetic activity was seen in epithelial and stromal cells throughout the prostate, rather than only in the distal segment. At Days 10 and 20, significantly higher percentages of epithelial and stromal cells were labeled in the distal than in the proximal segments; but at Days 45 and 60, the percentages of labeled epithelial and stromal cells in the distal, intermediate, and proximal segments were similar. Thus, in all segments, and at all ages, substantial labeling was seen throughout the prostate. These data suggest that the prostate grows in both length and width throughout postnatal development, reminiscent of the growth of a tree. PMID- 1756215 TI - Immunocytochemical evidence for production of luteinizing hormone and follicle stimulating hormone in separate cells in the bovine. AB - In all mammalian females, follicular growth and maturation are essentially dependent on the pituitary gonadotropins, FSH and LH. These glycoprotein hormones have many similarities, but their action, based on high affinity binding to specific membrane receptors, are quite different. The purpose of this study was to perform a sensitive localization of FSH and LH in secretory granules of gonadotrophs using highly specific antisera. This morphological study included light microscopy (PAP) and electron microscopy (immunogold single and double labeling) procedures. Histologically, approximatively 11.5% of cells were positive for LH, whereas only 5.4% of cells were positive for FSH. With the electron microscope, single labeling allowed identification of morphologically distinct LH-containing cells and FSH-containing cells. Double immunostaining confirmed that no cells contained both hormones. The finding that FSH and LH are produced in separate pituitary cells is in agreement with recent studies that have suggested a specific role and regulatory process for gonadotropins in the bovine species. PMID- 1756216 TI - [The diagnosis of approximal caries--a comparison of clinical, fiber optic and x ray diagnostic procedures (the diagnosis of approximal caries)]. AB - A comparison of the efficiency of fibre-optic transillumination with clinical and radiographic diagnosis of proximal caries in posterior teeth was carried out on 186 subjects aged 12 to 17 years. The proportion of diagnosed proximal lesions detected by fibre-optic transillumination was two times more often than by clinical examination while the increase in lesion detection by bitewing radiography was more than threefold. Taking radiographic diagnosis as the validating criteria, the sensitivity of clinical examination was 0.30 and of fibre-optic transillumination 0.68 resp. The specificity was 0.99 for both examinations. In patients with low prevalence of proximal caries and good preventive dental care fibre-optic transillumination should be used as an additional method before using of regular radiographic diagnosing of proximal caries. PMID- 1756217 TI - [The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial]. AB - The aim of this randomized, double-blind study was to measure the cariostatic effect of Bifluorid 12 (VOCO GmbH), containing 6% sodium fluoride and 6% calcium fluoride and Laweflour-Schuttellack (LAW), containing 5% sodium fluoride in comparing of placebo varnish. The caries study included 400 schoolchildren, aged 12-14 years. The tests according to the DMFS were carried out by two independent examiners. The 400 children were divided into 3 test and 1 placebo group, each group consisting of 100 subjects. After two years there was a significant inhibition of caries increment in all test groups compared to placebo group. Percentage caries reduction ranged from 25 to 30%. The highest effect was stated at proximal surfaces. PMID- 1756218 TI - [The development of methods for the objective assessment of occlusal parameters]. AB - For reasons of different data in literature on occlusal parameters and their metric registration, at the beginning of the 80's two methods independent of each other were developed--the capacity measuring method and the quasiplanimetry method to register the total occlusal contact area and the number of occlusal surfaces of contact at dental casts. The results obtained independently from each other showed a high degree of correspondence. That's why the method of quasiplanimetry was further developed and used for the direct analysis of enorally obtained wafers of different characteristic. The method is improved now with a modern system of digital analysis. The results obtained up to now admit the conclusion that the occlusion of the teeth represents an individual condition of high variability. With the reproducible method used individual occlusal parameters can be numerically registered. PMID- 1756219 TI - [Surgery before orthodontic treatment: a concept for timing the combined therapy of skeletal dysgnathias]. AB - Postsurgical orthodontic treatment will prevent several disadvantages of the presurgical orthodontic approach: 1. Orthodontic tooth-movements do not interfere with compensatory biological responses. 2. The dental arch alignment is similar to the procedures of any class-I-orthodontic treatment; i.e. dental movements can be based on an already corrected skeletal relation. 3. A possible postsurgical relapse may be easily compensated within the postsurgical orthodontic treatment. Presurgical corrections of dento-alveolar discrepancies are only required to limit an excessive vertical disclusion necessary for a correct sagittal and transverse positioning of the jaws. PMID- 1756220 TI - [Gingivectomy]. AB - The gingivectomy is the oldest surgical approach in periodontal therapy. During the centuries, the technique has been modified. Just at the middle of our century, gingivectomy was the most important surgical method in periodontal treatment. Indication for performance of the gingivectomy is the complete elimination of the periodontal pocket (gingival overgrowth/e.g. hyperplasia, subgingival caries, subgingivally located crown margins. The physiologic design of the free gingival margin by surgical means, gingivoplasty, must be taken under consideration. Depending on the long and painful healing for the patient, gingivectomy should be preserved for the indications above. Wherever possible, is recommended a flap procedure like the apically repositioned flap. PMID- 1756221 TI - Postulates defining pathogenic autoantibodies and T cells. PMID- 1756222 TI - In vivo effects of neonatal administration of antiidiotype antibodies on experimental autoimmune myasthenia gravis. AB - The in vivo effects of neonatal administration of varying doses of anti-idiotype antibodies on serum anti-acetylcholine receptor (AChR) antibody titers, idiotype expression, and disease severity was studied in experimental autoimmune myasthenia gravis. Polyclonal affinity purified anti-idiotype antibodies and monoclonal anti-idiotype antibodies directed at anti-AChR monoclonal antibody 65 were administered in dosages varying from the nanogram to the microgram range. Mab 65 is directed against the main immunogenic region of mammalian AChR. In 1 out of 4 experiments administration of a nanogram dosage of anti-idiotype antibodies led to an enhanced anti-AChR antibody response after immunization with AChR. But no enhancing effect on idiotype expression could be demonstrated during this experiment. Adoptive transfer of spleen cells from rats pretreated with a nanogram dosage of anti-idiotype antibodies resulted in an significantly increased antibody response against rat AChR after immunization. From these experiments we conclude that in vivo administration of polyclonal or monoclonal anti-idiotypes does not reproduceably modify the serum antibody level against the acetylcholine receptor, nor influences the idiotype profile of the immune response. Secondly, the idiotype mediated manipulation of the immune response against large antigens, like the acetylcholine receptor, is clearly more complicated than that against small haptens. Adoptive transfer models, might be helpful in analysing the possibilities of anti-idiotype treatment in myasthenia gravis in more detail. PMID- 1756223 TI - Binding of peripheral blood and thyroidal T lymphocytes to thyroid cell monolayers: possible role of "homing-like" receptors in the pathogenesis of thyroid autoimmunity. AB - The specific binding of blood lymphocyte populations to non-antigenic receptors on high endothelial cells in peripheral lymphoid organs is well established. Such "homing" receptors in target tissues may also play a role in the early phase of organ specific autoimmunity. In this study binding of peripheral blood and thyroid-derived T cells to human thyroid (THY) cells was examined. Binding was measured as the percentage 51Cr-labelled T cells bound to THY monolayers. Interferon-gamma (IFN-gamma) enhanced the binding of peripheral blood T cells (PBL-T) from patients with Graves' disease (GD) and normals, but not from patients with Hashimoto's thyroiditis (HT), to allogeneic THY monolayers. The binding of T cells from patients with HT to untreated allogeneic THY monolayers was significantly greater than that for T cells from patients with GD or normals. TSH inhibited the IFN-gamma enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n = 5) and autologous (n = 4) THY monolayers. Intra-thyroid T cells (ITL-T) bound to autologous THY monolayers significantly more than PBL-T from the same patient, while ITL from patients with HT or Graves' disease bound more than their PBL-T to both allogeneic and autologous THY monolayers. ITL-T, but not PBL-T, bound significantly more to autologous THY than to autologous thyroid-derived fibroblast monolayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756224 TI - Non-polarized cell surface expression of HLA-A,B,C and HLA-DR antigens in Graves' thyroid follicle cells. AB - The intrathyroidal distribution and cell surface location of HLA-A,B,C and HLA-DR antigens was studied in polarized thyroid follicle cells from Graves' (n = 11) and normal (n = 3) thyroid tissue, using light and electron microscopy. Cryosections and isolated, open follicle segments were incubated with monoclonal antibodies against HLA-A,B,C and HLA-DR antigens and with patient sera containing autoantibodies against the microsomal antigen/thyroperoxidase. Immunoreactivity for HLA-A,B,C and HLA-DR on isolated thyroid follicle cells was frequently detected in Graves' disease, but absent in normal glands. There was a large variation in the immunolabelling between follicles as well as between different glands. Both HLA-A,B,C and HLA-DR immunoreactivity were detected on the apical and the basal surface of the follicle cells. Microsomal antigen/thyroperoxidase immunoreactivity was restricted to the apical cell surface. In contrast to normal tissue, HLA-DR positive cells with a dendritic or macrophage-like morphology were frequent in Graves' tissue. These cells adhered directly to the basal surface of isolated follicle segments. We conclude that HLA antigens are, unlike thyroid specific plasma membrane constituents, expressed in a non-polarized manner at the surface of the follicular epithelium. These observations might have implications on the immune recognition of thyroidal autoantigens in Graves' disease. PMID- 1756225 TI - Inhibition of protein-kinase C in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: effect on spontaneous immunoglobulin production. AB - Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the spontaneous secretion of immunoglobulin (Ig) molecules, many of which are autoreactive. We have previously shown (Biochem & Biophys. Res. Comm. (1989) 161: 1319-1326) that normal human peripheral blood mononuclear cells (PBMCs) can be stimulated to secrete large quantities of Ig upon incubation with the protein kinase-C activator 1 oleoyl-2-acetyglycerol (OAG). Specific blockage of protein kinase C with the isoquinoline sulfonyl piperazine compound (H-7) inhibited the OAG-induced Ig production. In experiments reported here, PBMC of 5 patients with active SLE produced high levels of IgG spontaneously in culture. PBMC of 6 inactive SLE patients and 7 normal control subjects produced comparable low levels of IgG spontaneously. Pokeweed mitogen (PWM) stimulation of PBMC in inactive SLE and control groups, but not active SLE patients produced markedly enhanced IgG production. The lack of response to PWM stimulation in active SLE patients is likely due to inherent maximal stimulation of active SLE B-cells. In addition, we examined the ability of H-7 to inhibit both mitogen-stimulated (normal and inactive SLE) and spontaneous (active SLE) Ig production. In other experiments, we also examined the ability of the isoquinoline sulfonamide (HA 1004), a potent inhibitor of cAMP-dependent protein kinase to regulate mitogen stimulated and spontaneous Ig production in the patient groups indicated above. H 7 significantly inhibited PWM stimulated Ig production in normal (P less than 0.0001) and inactive SLE patients, (P less than 0.040) suppressing PWM stimulated levels to spontaneous levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756226 TI - Different nature of the proliferation defects of GLD, LPR and MEV C57BL/6 mouse lymphoid cells. AB - The three non-allelic gld, lpr and mev mutations in the mouse all lead to profound immunodeficiency besides a splenomegaly and a generalized autoimmunity. Spleen cells from young B6 gld, B6 lpr and B6 mev mice all display a decreased proliferative response to the T-cell mitogen concanavalin A (ConA), but the nature of the deficiency seems very different. No restoration of proliferation could be obtained by adding exogenous recombinant rIL2 to ConA-treated mev spleen cells, this lack of IL2-responsiveness suggesting a lack of (functional) IL2 receptors. In young mice of both gld and lpr strains, a B6 wild-type level of proliferation could be reached by rIl2 addition to ConA-treated spleen cells, this normal responsiveness to exogenous IL2 suggesting a normal expression of IL2 receptors. The endogenous IL2 production by ConA-treated spleen cells decreased very much with ageing in both B6 gld and B6 lpr mice. Yet, IL2 production in young mice revealed an earlier deficiency of the B6 lpr mice: the young B6 gld IL2 levels reached about 60% of age-matched B6 wild cell levels, but the B6 lpr levels reached 14% only. Finally the addition of exogenous rIL2 to ConA pretreated cells from old B6 gld and B6 lpr mice, while enhancing the proliferative responses, could not restore the B6 wild-type levels. This suggests that, with ageing, the expression of functional IL2-receptors may become as abnormal in these gld and lpr mutants as it is from birth in the mev mutant mice. PMID- 1756227 TI - New postulates of autoimmunity--are they bona fide? PMID- 1756228 TI - Postulates defining pathogenic autoantibodies and T cells. PMID- 1756229 TI - Serum IL-2 level in rheumatoid arthritis: correlation with joint destruction and disease progression. AB - Understanding of T cell dysfunctions in rheumatoid arthritis (RA) may help to elucidate the pathophysiology of this disease. Cytokines determinations may be a promising approach and could represent a simple mean of quantifying RA immunological dysfunctions. In this study, interleukin-2 (IL-2) measurements were performed in sera of 74 RA patients to evaluate the potential use of this method to monitor "disease activity" and/or prognosis. Although the serum IL-2 levels of patients in active disease stage proved to be somewhat lower than those from patients with inactive disease, the difference was not significant. In our study, however, the serum IL-2 concentration was correlated with the circulating immune complexes level. In addition, patients with the highest serum IL-2 levels exhibited the poorest radiological stages and these same patients were often not receiving any disease modifying antirheumatic drugs (DMARD). Our results demonstrate that serum IL-2 level may be elevated in certain RA conditions. A better understanding of this phenomenon, especially the consequences of disease duration, could be of interest in the follow up and the prognosis of the disease. PMID- 1756230 TI - Expression of tumor necrosis factor-alpha and -beta transcripts in embryonal carcinoma and trophoblast cell lines: inflammation-like state as possible regulatory mechanism for ontogenesis. AB - TNF-alpha and TNF-beta are both involved in inflammation which regulates homeostasis in adults. We examined the mRNA expression of TNF-alpha and TNF-beta in murine embryonal carcinoma (EC) cell lines (PCC3, PCC4, ECA2 and F9) and trophoblast cell line (PL/B6) using a combined system of reverse transcription and polymerase chain reaction. Four lines of EC cells and PL/B6 expressed mRNA of both TNFs. Moreover, mRNA expression of two types of TNF-receptor and transcription factor NF-kappa B, both of which mediate a part of the biological function of TNFs, were also detected in EC and trophoblast cells. In order to clarify whether other cytokines may form a network during embryonal development, we also examined the expression of transcripts of inflammatory cytokines produced by activated macrophages (IL-1 alpha, IL-1 beta and G-CSF) or by T lymphocytes (IL-3 and IFN-gamma) in adult. We found that no IL-1 alpha transcript was expressed in any of the cell lines examined whether differentiated or not. Contrary to this, the transcript of G-CSF was continuously expressed in all cell lines, and those of IL-1 beta, IL-3 and IFN-gamma were slightly expressed in some cell lines. PMID- 1756231 TI - Aberrations in interleukin-1 expression in oncogene-transformed fibrosarcoma lines: constitutive interleukin-1 alpha transcription and manifestation of biological activity. AB - We have examined interleukin-1 (IL-1) expression in a series of oncogene transformed NIH-3T3 fibroblastoid cell lines. In contrast to primary fibroblasts where IL-1 is inducible, NIH-3T3 cells (clone 490N3T) transcribe the IL-1 alpha gene constitutively. Transformation of 490N3T cells by the v-mos or v-H-ras oncogenes appears to either enhance or suppress IL-1 alpha transcription, respectively. In v-myc transfected cells, constitutive IL-1 activity could be detected intracellularly. An additional membrane-associated form of IL-1 was observed in lines transformed by protein-kinase (PK) encoding oncogenes, such as TPR-met, c-met, v-src, v-abl, v-mos and v-raf. In none of the lines tested the secreted form of IL-1 activity could be detected, and no constitutive expression of IL-1 beta was observed. Our studies manifest aberrations in IL-1 expression in oncogene-transformed fibroblastoid cell lines, detected at different regulatory levels, such as transcription, translation and compartmentalization. IL-1 is a potent pleiotropic cytokine, with regard to its target cell specificity and spectrum of activities; growth promoting effects of IL-1 on fibroblasts were reported and on the other hand this cytokine activates various anti-tumor mechanisms. Thus, endogenous IL-1 expression by tumor cells may affect the neoplastic phenotype, either by influencing the growth of the malignant cells or by modifying tumor-host interactions. PMID- 1756232 TI - The role of monocytes in the induction and regulation of IFN-gamma production by lectin-activated human T lymphocytes. AB - The data presented show that the production of interferon gamma (IFN-gamma) by pokeweed mitogen (PWM)-activated T lymphocytes requires monocytes and that the amount of lymphokine produced depends on the number of monocytes present in the culture. Accessory function of monocytes was independent from their ability to secrete IL-1 but required cell-cell contact, since blocking of adhesion molecules reduced the IFN-gamma production. Furthermore, production of IFN by lectin preactivated T lymphocytes could not be triggered by IL-2 but also required monocyte-T cell interaction. PMID- 1756234 TI - Movement related brain potentials accompanying a non-productive voluntary action in humans. AB - This study assessed the effects of training and ability to execute a voluntary movement upon movement-related brain potentials (MRBPs). A self-paced thumb flexion initiated a sequence of autotriggered electrical stimuli over the median nerve that caused a twitch opposing the intended thumb extension. The MRBPs had earlier onsets during the first runs of skill acquisition than during later training sessions; they occurred earlier when they preceded a stimulus train than when they preceded a single stimulus; the onset was earlier over the vertex than over the premotor area. MRBP duration was longer during train stimulation when a voluntary effort had to be maintained against tetanic contraction. MRBP amplitude did not reflect task requirements under these experimental conditions. PMID- 1756233 TI - Specific regulation of the 100 kDa 2-5 A synthetase by protein kinase C. AB - The 2-5 A synthetase is a system of several isozymes, whose expression is induced by interferons (IFNs) at the transcriptional level. These enzymes mediate part of the antiviral effects of IFNs and are thought to have an important role in cell growth or differentiation. The different isozymes -100, 69, 46 and 40 kDa expressed in human cells, or the 105, 71 and 43 kDa expressed in mouse cells--are induced by IFNs with cell type specificity, and exhibit individual differences in their biochemical and enzymatic properties. Here we studied the effects of the tumor promoter phorbol ester (TPA), or the calcium ionophore A23187, on the pattern of expression of 2-5 A synthetase isoforms, and found a role of protein kinase C (PKC) in the adjustments of this pattern. We show that in HeLa cells the 100 kDa 2-5 A synthetase can be specifically induced by short term treatments with TPA, or with the calcium ionophore A23187. Induction of the 100 kDa form is mainly post-transcriptional. By contrast long term treatments by TPA resulting in the down regulation of PKC, or employing H7, a specific PKC inhibitor, reduced drastically the induction by IFNs of the 100 kDa enzyme in HeLa or fibroblast cells, without reducing the expression of the other forms. Moreover, using a mouse Swiss 3T3 cell line in which the cDNA coding for PKC-alpha was introduced, leading to its overexpression, we could show that the mouse 105 kDa synthetase was constitutively expressed. Thus, a direct correlation was found between the expression of PKC-alpha and the specific induction of the 105 kDa form. Neutralization of autocrine IFNs by antibodies reduces the expression of the 105 kDa species. However the autocrine IFN in the medium of the cells overexpressing PKC is not able to induce 2-5 A synthetase in control transfected Swiss 3T3 cells. Thus, IFN is probably essential for the expression of the 105 kDa synthetase but may be not produced in sufficient amounts to induce the 105 kDa protein. PMID- 1756235 TI - Very low concentrations of acetylcholine and GABA modulate transmitter responses. AB - Acetylcholine and GABA, at extremely low concentrations (10(-14) to 10(-8) M) which do not induce electrical responses, each modulate the chloride-dependent responses of Aplysia neurons to higher concentrations of the same transmitters. Low concentrations of acetylcholine cause a reduction of the response to both acetylcholine and GABA, while low concentrations of GABA cause a facilitation of responses to both acetylcholine and GABA. These effects have a clear threshold, are slow in onset, reversible with prolonged washing, and blocked by cooling. PMID- 1756236 TI - The corticotectal projection of the rat established in organotypic culture. AB - To study the mechanisms involved in the formation of neural projections we established an in-vitro model system, consisting of the projection from visual cortex (VC) to colliculus superior (SC) in organotypic slice culture. The typical laminar structure of both brain areas was well conserved in-vitro. A projection from VC to SC was reliably formed. Cortical projection neurons retrogradely stained by DiI were situated in layer V and showed a prominent apical dendrite with a tuft in layer I. No projection from SC to VC was established. Cortical terminal arborizations revealed by anterograde staining were often organized in layers. We conclude that the typical anatomical characteristics of the corticotectal projection are preserved in-vitro. PMID- 1756237 TI - Evidence for microtubule capture by filopodial actin filaments in growth cones. AB - We have studied, by immunofluorescence, the organization of microtubules in growth cones in dissociated neuronal cell cultures. Growth cones have a large pool of soluble tubulin and in conventionally fixed cultures the entire growth cone, including the filopodia, is labelled with tubulin antibodies, thus obscuring the microtubules. In contrast, in cultures fixed with fixatives containing detergent, the soluble pool of tubulin is removed allowing clear views of the microtubules. On entering the growth cone from the neurite, microtubules splay out and may extend as far as the base of filopodia. In most growth cones, one or more individual microtubules extend into filopodia, aligning with the parallel bundle of microfilaments. This observation suggests one way growth cone motility and neurite advance may be coupled. PMID- 1756239 TI - Cortical fields participating in form and colour discrimination in the human brain. AB - In order to map the anatomical structures participating in the analysis and processing of visual information related to discrimination of form and colour, we measured with positron emission tomography (PET) regional cerebral blood flow (rCBF) as an indicator of metabolic activity in ten right-handed volunteers during visual discrimination tasks, namely reference, form and colour tasks. Form discrimination specifically increased rCBF bilaterally in the inferior temporal and cingulate gyri, and in the left superior temporal, left occipital lateral, and left angular gyri, whereas colour discrimination did so in the left occipital superior and lateral, left parahippocampal, left occipito-temporal medial (lingual), and left superior parietal gyri, and the right precuneus. PMID- 1756238 TI - NGF increases cortical acetylcholine release in rats with lesions of the nucleus basalis. AB - Rats received a unilateral lesion of the nucleus basalis by infusion of ibotenic acid. Two weeks after the lesion, osmotic minipumps were implanted, that infused 1 microgram human recombinant nerve growth factor (NGF) or cytochrome-C per day into the lateral ventricle. After four weeks of treatment, release of acetylcholine was measured in the frontal neocortex by means of in-vivo microdialysis. Release was decreased by 75% on the lesioned side; perfusion with 100 mM KCl increased release on the intact side by 130% and on the lesioned side by 80%. Treatment with NGF increased release on the lesioned side twofold, but had no effect on release on the intact side. PMID- 1756240 TI - Identification of angiotensin II receptor subtypes in human brain. AB - The present study assessed the binding characteristics of [125I]angiotensin II to slices of human cerebellum adhered to glass slides using quantitative receptor autoradiography. Specific [125I]angiotensin II binding, defined by the inclusion of unlabelled angiotensin II (1.0 microM), was detected in the molecular layer of the cerebellum (0.09 +/- 0.02 fmol/mg tissue equivalent, mean +/- s.e.m., n = 3). The angiotensin II-2 receptor subtype selective ligand, PD123177, competed for approximately 65% of the specific binding in the molecular layer whilst the remainder of the specific binding was displaced by the angiotensin II-1 receptor subtype selective ligand, DuP753. It is concluded that angiotensin II receptor subtypes exist in human brain tissue and provide potential therapeutic sites of action. PMID- 1756241 TI - The supraoptic nuclei in vasopressin and hemodynamic responses to hemorrhage in rats. AB - Cardiovascular and vasopressin (AVP) responses to hemorrhage were studied in rats with lesions of the hypothalamic supraoptic nuclei (SONL). Bleeding caused hypotension and increase in heart rate (HR) and AVP. SONL rats failed to fully recover from bleeding as compared to normal rats. Plasma AVP in SONL rats was in the normal in basal conditions, but failed to increase to levels attained in normal rats throughout the post-hemorrhage period. These data suggest that the supraoptic nuclei are the primary regulatory sites for AVP release in response to hemorrhage and that lack of adequate AVP release significantly retards blood pressure recovery after bleeding. PMID- 1756242 TI - Binocular probability summation in a choice reaction-time task in pigeons. AB - We present evidence for binocular summation in pigeons in a choice reaction time paradigm. Considering binocular vision as the result of a race between the equivalent eyes, pigeons can adopt both a 'subject by subject' and a 'trial by trial' race model, and binocular advantage can be attributed merely to a probability summation. Pigeons were tested on a visual discrimination task in which the time for detection was gradually reduced and a quick response was required. The time presentation of a small black spot could vary from 2000 ms to the shortest value (157-226 ms) allowing maintenance of a satisfactory performance criterion. PMID- 1756244 TI - A model of respiratory rhythm generation. AB - A new hypothesis is proposed to explain the generation of respiratory rhythm by the respiratory neurons of the medulla. The basis of the oscillator is a mutual inhibition between early-burst inspiratory, propriobulbar neurons and Botzinger complex expiratory, bulbospinal neurons, with only the early burst inspiratory neurons possessing adaptive properties. Only one theoretical connection, unsupported by experimental observations, needs to be assumed for this model, that of an inhibitory connection from Botzinger complex expiratory neurons to early-burst inspiratory neurons. A mathematical simulation of the model was used to test the hypothesis. The oscillating patterns of activity produced by the model were similar to those observed experimentally in these neurons. It is therefore concluded that, based on reasonable assumptions, the proposed hypothesis will produce oscillations similar to those of respiration. PMID- 1756243 TI - Long-term enhancement of REM sleep following cholinergic stimulation. AB - A six day long increase in rapid eye movement (REM) sleep followed the unilateral microinjection of a single dose of the cholinergic agonist drug carbachol into the brain stem of cats. Effective drug injection sites were localized to the pontine peribrachial region containing cholinergic choline acetyltransferase (ChAT) labeled neurons. At the peak of the effect, which occurred 24-28 h post injection, the relative amount of time devoted to REM sleep tripled, resulting in an absolute time increase from 3.12 to 11.28 h REM sleep per day. This pronounced and prolonged REM sleep increase was associated with marked enhancement of ponto geniculo-occipital (PGO) waves and with PGO burst cell activity unilateral to the site of injection. PMID- 1756245 TI - m-Chlorophenylpiperazine enhances neophobic and anxious behaviour in mice. AB - 1-(3-Chlorophenyl)piperazine (mCPP) reduced novelty-seeking behaviour as well as the number of rears in mice confronted with a free exploratory test. Moreover, mCPP was found to decrease the time spent by mice in the lit box and the number of transitions in a two-box light/dark choice situation validated for the detection of anxiolytic or anxiogenic drugs. These results suggest that mCPP enhances emotional responses towards novel and aversive places. Since mCPP has been reported as a 5-HT1C receptor agonist, it can be hypothesized that increased activity of serotonin may play a role in regulating certain forms of emotional behaviour in animals. PMID- 1756246 TI - Superoxide dismutase halts cycling of murine erythroid progenitor cells prior to S phase in vitro and possibly in vivo. AB - Mice of the C57BL/6 (B6) strain show a much lower proportion of marrow erythroid progenitor cells (BFU-E) in DNA synthesis in vivo than mice of the congeneic B6S strain. However, when assayed in vitro marrow cells from both strains show high proportions of BFU-E in S-phase. BFU-E from normal B6 mice have been previously shown to be specifically inhibited from entering S-phase in vitro by the antioxidant enzyme superoxide dismutase (SOD), however, in this study we have found that BFU-E taken from the marrow of B6S mice or B6 mice which have been subjected to bleeding are insensitive to SOD inhibition in vitro. Comparisons of results from in vivo and in vitro cycling assays done with cells from both strains indicate that a large proportion of marrow BFU-E in normal B6 mice are halted in the pre-S portion of the cell cycle in vivo, and these halted cells are prevented from going into S-phase in vitro by SOD. The insensitivity to SOD inhibition shown by BFU-E from B6S and bled B6 mice can be attributed to the absence of accumulation of SOD-susceptible cells in pre-S phase in these mice in vivo, and there is evidence to suggest that the difference in BFU-E cycling seen in vivo may be due to interactions between SOD and factors which stimulate cycling of BFU-E. PMID- 1756247 TI - Factor with erythroid burst-promoting activity in human urine unlike other hematopoietic growth factors. AB - A factor with burst-promoting activity (BPA) stimulates the formation of erythroid bursts in the presence of erythropoietin, acting on early erythroid progenitor cells (erythroid burst-forming units, or BFU-E). Here we investigated the biological properties of this factor partially purified from the urine of anemic patients. The human urinary factor did not cause the formation of late erythroid progenitor cells (erythroid colony-forming units, or CFU-E) or enhance such colony formation in the presence of erythropoietin. Thus, the urinary factor was a different substance from erythroid potentiating activity and from activin, which act on both BFU-E and CFU-E. The urinary factor promoted the colony formation of BFU-E from both humans and mice, but the human hematopoietic growth factors such as recombinant interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor did not stimulate the formation of BFU-E derived colonies from mice. The results suggested that the factor in the urine of anemic patients was different from the hematopoietic growth factors identified so far. PMID- 1756248 TI - The effects of subcutaneous deferoxamine administration on renal function in thalassemia major. AB - To assess the effects of deferoxamine (DFO) on the kidneys, we studied 27 patients with thalassemia major on chronic subcutaneous (s.c.) DFO therapy. In 41% of the patients glomerular filtration rate (GFR) values were above the normal range. In a previous study similar findings were reported for thalassemia patients who did not receive DFO. The subcutaneous administration of DFO was associated with a clinically significant decrease in GFR in 40% of the patients and in a mild decrease in another 40%. In all cases of severe decreases in GFR, it tended to return to baseline values upon discontinuation of DFO. There was a significant increase in urine volume during DFO therapy. These changes are consistent with our previous observation in humans and dogs receiving high dose i.v. DFO, albeit milder. PMID- 1756249 TI - Expression of three cell proliferation-associated antigens, DNA polymerase alpha, Ki-67 antigen and transferrin receptor in nodal and cutaneous T-cell lymphomas. AB - We studied the expression of three cell proliferation-associated antigens: DNA polymerase alpha, Ki-67 antigen, and transferrin receptor, in 35 T-cell lymphomas of nodal origin (T-NL) and 40 cutaneous T-cell lymphomas (CTCL). Immunohistochemical staining was carried out on frozen tissue sections of these specimens using three monoclonal antibodies, DAKO-PC, CL22-2-42B (DNA polymerase alpha), and OKT9. The proportion of cells positive for CL22-2-42B, DAKO-PC, or OKT9 among all tumor cells was correlated with four histologic subtypes: malignant lymphoma (ML), diffuse, small; mixed; large; and large cell immunoblastic in both T-NL and CTCL. A strong correlation was noted between positivity for CL22-2-42B and that for DAKO-PC or OKT9. On the other hand, no difference in the expression of these three antigens was noted between T-NL and CTCL in the high, intermediate or low grade-malignancy group. In CTCL as well as in T-NL, cells positive for CL22-2-42B, DAKO-PC or OKT9 were significantly more numerous in the high-grade group than the intermediate-grade group, and in the intermediate-grade group than the low-grade group. Furthermore, a significant correlation between survival period and the number of CL22-2-42B-positive cells was noted when the T cell malignancies, CTCL and T-NL were considered (t value = 2.015, p less than 0.05). Thus, the expression of DNA-polymerase alpha, Ki-67 antigen or OKT9 seems to well reflect the biological behavior and/or clinical prognosis of T-cell lymphoma. PMID- 1756250 TI - Geographic clustering of myeloma in Tokushima. AB - Between 1978-1988, seven cases of multiple myeloma were found in T Town (population 9,000), which is located at the mouth of a large river within the boundaries of Tokushima City, Japan. This is a significantly high incidence, 7.06 per 100,000 as compared with an incidence of 1.20 in Tokushima City itself and 1.53 in Japan as a whole. The clinical and laboratory features of these patients were typical of myeloma. Although the causes of this small but apparent cluster of multiple myeloma remain obscure, the fact that five of the seven patients had been working for long periods as fishermen was notable. PMID- 1756251 TI - Inhibition of platelet aggregation by low concentrations of sodium fluoride. Significance of the intracellular calcium ion concentration. AB - Sodium fluoride activates platelets but its mechanism of action has not yet been completely identified. We examined the effect of a low concentration of sodium fluoride (which could not cause aggregation) on thrombin-induced changes in the intracellular calcium ion concentration ([Ca2+]i). In the presence of 1 mM extracellular Ca2+, preincubation with a low concentration of sodium fluoride decreased the peak of the thrombin-induced elevation of [Ca2+]i, when measured with aequorin. When [Ca2+] was measured using fura-2, preincubation caused no marked changes in its peak, but the later changes that were thought to mainly reflect extracellular Ca2+ influx were inhibited. The inhibitory mechanism of sodium fluoride appears to depend on reducing extracellular Ca2+ influx. Aequorin appears to reflect [Ca2+]i near the cell membrane and is thus easily affected by the extracellular Ca2+ influx. PMID- 1756252 TI - Clinical evaluation of recombinant human factor VIII (BAY w 6240) in the treatment of hemophilia A. AB - A pilot clinical trial was conducted in five patients with severe hemophilia A to evaluate the safety and efficacy of a recombinant human factor VIII preparation, BAY w 6240 (rFVIII). In a comparative pharmacokinetic study of rFVIII and a plasma-derived factor VIII preparation (pdFVIII), the mean t1/2 values for rFVIII at week 1 and week 13 were 16.8 and 14.4 h, while this value for pdFVIII at week 2 was 16.9 h. There were no statistical differences between these values. The mean in vivo recovery rates of rFVIII were comparable to those of pdFVIII. When rFVIII was administered prophylactically three times a week for 4 weeks, no bleeding episodes were observed. Seventy-four bleeding episodes were assessed during the 6-month treatment period. The efficacy rate of the hemostatic effect was confirmed to be 95.9%. No adverse reactions attributable to rFVIII were observed in a total of 178 infusions. Neither FVIII-inhibitors nor antibodies to foreign proteins were detected. Vital signs and laboratory findings showed no significant changes attributable to rFVIII. These results suggest that rFVIII is safe and efficacious as replacement therapy for hemophilia A. PMID- 1756253 TI - Plasma coagulation and fibrinolysis parameters in patients with collagen diseases, and analysis of the multimeric structure of von Willebrand factor (vWF). AB - We studied the relationship between vascular complications and coagulation and fibrinolysis parameters in 75 subjects with collagen diseases. Thirty normal healthy persons served as controls. We found that patients with collagen diseases were in a state of a hypercoagulation and hyperfibrinolysis. In SLE (systemic lupus erythematosus) in particular, coagulation and fibrinolysis parameters appeared to be indices of vascular complications. Increases in the levels of thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin (PIP) were particularly associated with proteinuria, while increases in fibrinopeptide A (FPA) levels were associated with Raynaud's phenomenon. Administration of glucocorticoid seemed to improve the hypercoagulation and hyperfibrinolytic states of patients with collagen diseases. Analysis of the multimeric structure of von Willebrand factor (vWF) revealed a tendency for large and intermediate multimers (LIM) of plasma vWF to increase in SLE patients with accompanying vascular complications, whereas such increases were not observed in SLE patients without any vascular complications. Therefore, analysis of the multimeric structure of vWF appeared to be a useful indicator of vascular complications in collagen diseases. PMID- 1756254 TI - Chronic lymphocytic leukemia associated with von Recklinghausen neurofibromatosis. AB - We report a 62-year-old female, with von Recklinghausen neurofibromatosis and chronic lymphocytic leukemia, whose mother and son both had neurofibromatosis and died of digestive tract cancers. The patient died of pneumonia 3 years after the initiation of therapy. Leukemia reported in association with neurofibromatosis are predominantly nonlymphocytic and limited to childhood. The type of association found in our patient has not been reported previously. PMID- 1756255 TI - Natural history of human breast cancer: recent data and clinical implications. AB - This study of the natural history of human breast cancer was based on the analysis of a series of 3000 patients treated by radical mastectomy at a single institution (Institut Gustave Roussy) at a time when adjuvant chemotherapy was not prescribed. The follow-up of the patients ranged from 15 to 30 years; for each patient the tumor size, the number of involved axillary nodes, and the histological grade were prospectively registered. A highly significant correlation was found between tumor size and the probability of distant metastatic dissemination. The distribution of tumor sizes at metastatic spread was log-normal with a median diameter equal to 3.5 cm. The patients were subdivided into 3 groups according to the histological grade. In each subgroup there was a significant correlation between tumor size and the probability of distant spread; the distributions were log-normal and the median size was markedly larger for grade 1 tumors. Moreover the proportion of grade 1 tumors was higher in small tumors than in large ones while the reverse was observed for grade 3 tumors; these data suggest that during their growth tumors progress towards higher grades. One of the chief fundamental characteristics of a tumor seems to be its propensity for axillary node invasion. The orderly pattern of nodal involvement makes it possible to calculate the tumor size at invasion of the first axillary node in each subset of patients. A strong and highly significant correlation exists between the size of the tumor at initiation of distant metastasis and at invasion of the first lymph node. However the capacity for lymphatic spread is, on average, acquired much earlier than the capacity for metastatic spread. With a simple model based on these data it was possible to compute the proportion of patients with occult metastases as a function of tumor size, histological grade, and number of involved axillary nodes. Early invasion of axillary nodes is associated with a rapid growth rate of the primary tumor (or a high S-phase fraction). However each of these variables has an independent prognostic significance; the S-phase fraction appears as one of the strongest prognostic indicators. A model of tumor growth was used to assess the impact of screening procedures on the proportion of patients with distant metastases. The predictions of the model are consistent with the results of the screening programs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756256 TI - Proliferative inhibition of human breast carcinoma cells by high concentration estradiol does not alter radiosensitivity. AB - The proliferation of ER+ malignant mammary epithelial cells (MMEC), MCF-7 and T 47D, was markedly inhibited by 10 microM 17 beta-estradiol (E2), while the ER- line, MDA-MB-231, was minimally affected. This concentration of E2 did not alter the proportion of non-viable cells or the plating efficiency. The decrease in proliferation was not associated with any consistent alteration in the cell kinetic profile between lines, though there was clearly no dominant cell cycle re assortment after a two day incubation. Colony forming ability after exposure to ionizing irradiation was compared for proliferating and confluent MMEC to cells incubated in 10 microM E2 for two days. The presence of E2 resulted in no significant differences for any of the linear quadratic curve fitting parameters or for mean inactivation doses for both subconfluent and confluent cultures. Further, 10 microM E2 had no effect on the ability of cells to recover from split radiation fractions. There were no differences in the amount of DNA single strand break induction with E2, but there was a significant shortening in the repair halftime with E2 for the ER- MDA-MB-231 cells. Though high concentrations of E2 can markedly inhibit the proliferation of ER+ MMEC, this does not alter sensitivity to ionizing irradiation. PMID- 1756257 TI - Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67. AB - We performed immunohistochemical analyses of 568 breast/cancer specimens using Ki 67, a monoclonal antibody specific for a nuclear antigen present in proliferating cells. The specimens were divided into three groups (I-III) according to the proportion of Ki-positive cells detected. These findings were compared with features of tumor extension as well as with certain prognostic variables. There was no detectable correlation between Ki-67 reactivity and either tumor size or node involvement. In contrast, a statistically significant correlation was found between Ki-67 reactivity and tumor grading, in that G-I tumors had small growth fractions, while a high proportion of G-III tumors exhibited strong (group III) Ki-67 positivity. When growth fractions were compared with biochemical receptor status, a significant difference was detected between tumors with negative and positive findings for receptors. The same co-variation was observed with respect to the overexpression of neu-protein P185, with most neu-positive carcinomas being strongly positive for Ki-67 (group III). In the relapse cases examined, there was a close correspondence between Ki-67 reactivity and the duration of the disease-free period. Long-term observation of patients with primary breast carcinoma revealed that, with regard to overall survival, the less reactive groups I and II differed significantly from group III. With respect to disease free survival, no difference was detectable between Ki-groups II and III, but when these two groups together were compared with group I, a significant trend emerged. Similar results for both overall and disease-free survival were obtained for subgroups of pT2 and G-II carcinomas as well as for receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756258 TI - Coordinated expression of intermediate biomarkers for tumorigenic transformation in RAS-transfected mouse mammary epithelial cells. AB - Deregulated expression of the RAS oncogene is associated with tumorigenic transformation of mammary cells. Because of the complex, multiphasic nature of cancer progression, it is important to systematically identify the biomarkers specific for initiation, promotion, and progression of breast cancer. Mouse mammary epithelial cells (MMEC) were transfected with normal c-Ha-RAS proto oncogene (pH06N) and with mutant c-Ha-RAS oncogene (pH06T). The parental MMEC and the cloned transfectants pH06N1, pH06N2, pH06T1, and pH06T12 were evaluated for the acquisition of transformed characteristics by determining altered cellular metabolism of estradiol, increased ability for anchorage-independent growth, and ability to form tumors at the transplant site in athymic 'nude' mice. Persistent, functional integration of c-Ha-RAS was evidenced by the presence of a 1.2 kb c-Ha RAS transcript in the four transfectants but not in MMEC. All the transfectants also exhibited a substantial increase in the binding of c-Ha-RAS p21 to [alpha 32P] GTP relative to MMEC (P less than 0.003). The relative extent of estradiol metabolism leading to the formation of 16 alpha-hydroxyestrone was increased (P less than 0.004) in all the four transfectants. These four transfectants also showed a 100-400 fold increase in colony forming efficiency in 0.33% agar, relative to MMEC (P less than 0.0009), and formed rapidly growing tumors within 3 5 weeks of transplantation. Our results demonstrate that i) persistent expression of normal and mutant c-Ha-RAS can bring about tumorigenic transformation of mouse mammary epithelial cells; and ii) alteration in estradiol metabolism and acquisition of anchorage-independent growth precede the emergence of a tumorigenic phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756259 TI - Phase II evaluation of interferon added to tamoxifen in the treatment of metastatic breast cancer. AB - This phase II trial evaluated the clinical role of interferon (IFN) in overcoming tamoxifen (TAM) resistance in breast cancer. Twenty women and 1 man received recombinant alpha interferon (5 million units per meter squared intramuscularly, 5 times per week) plus TAM (10 mg orally, twice daily) for the treatment of metastatic breast cancer, either after failing tamoxifen therapy or as frontline hormonal therapy. Of the 9 evaluable patients with disease progression after an objective response to TAM, there were no partial or complete responses with the addition of IFN. Ten evaluable patients received TAM plus IFN as frontline hormonal therapy with 2 complete and 3 partial responses for an overall response rate (RR) of 50% (95% confidence interval = 19-81), a 71% RR for ER-positive patients (95% confidence interval = 29-96) and no responses in ER-unknown patients. Sixteen patients required dose reductions of IFN and 8 patients discontinued therapy due to toxicity. It is unlikely that the RR for TAM plus IFN is greater that than seen with TAM alone, or that the addition of IFN to TAM therapy can overcome clinical TAM resistance. PMID- 1756260 TI - A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer. AB - A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients each received 480, 800, and 1280 mg/d; 48 patients received 1600 mg/d. Of the 57 patients, 56 patients had had disease progression on prior hormone therapy, chemotherapy, or both. Twenty-seven patients had previously received standard dose MA (160 mg/d). Among the 37 patients with measurable disease, high-dose megestrol acetate (HDMA) produced 6 (16%) complete responses (CRs) and 6 (16%) partial responses (PRs); 11 patients achieved stable disease (SD). HDMA resulted in improvement or stabilization in 12 of the 20 patients with evaluable, non measurable disease. There were no responses among the 6 patients with liver metastases. Among the 27 patients who were previously treated with standard-dose MA, including 9 patients with primary treatment failure, HDMA resulted in 1 CR, 3 PRs, and 10 SD. Toxicities, which were mild and reversible, included fluid retention, hypertension, hyperglycemia, and mild congestive heart failure. Two patients had superficial phlebitis. The most profound side effect was weight gain which occurred in 43 patients (75%). This study suggests a dose-response relationship for MA in the treatment of advanced breast cancer. A randomized trial to determine the optimal dose is ongoing. PMID- 1756261 TI - Duct endoscopy and endoscopic biopsy in the evaluation of nipple discharge. AB - Microdochectomy is usually performed on patients with nipple discharge caused by intraductal proliferative lesions, such as intraductal papilloma and carcinoma. But this operation often sacrifices large amounts of normal mammary gland even when the lesion is a benign intraductal papilloma a few millimeters in diameter. We have developed duct endoscopy for the mammary duct system, and have reliably performed biopsies for intraductal proliferative lesions intraductally. From June 1989 to April 1990, we examined 22 cases by duct endoscopy, and performed endoscopic biopsy in 16 cases. The method of endoscopic biopsy is as follows. First, a bougie is inserted, without anesthesia other than Xylocaine jelly, into the orifice of the duct to enlarge it. Second, the outer cylinder and the inner needle are inserted; then the inner needle is removed, and the endoscope is inserted. After examination, the outer cylinder is moved up to the lesion to be biopsied and the endoscope is taken out. Then a sample is taken into the outer cylinder by aspiration. We diagnosed 10 cases of benign lesion and 5 cases of malignant lesion by cytological and/or histological examination. In conclusion, endoscopic biopsy, aided by duct endoscopy, is a useful and harmless diagnostic procedure in the evaluation of nipple discharge. PMID- 1756262 TI - Influence of age and comorbidity on treatment choice and survival in elderly patients with breast cancer. AB - To determine the effect of age and comorbid diseases on treatment choice and survival, the medical records of 300 breast cancer patients of 55 years and older were reviewed. All patients were admitted to the Netherlands Cancer Institute (NKI) for first treatment between 1980 and 1987. Patients were classified according to severity level of comorbid diseases. Physicians were found to treat women of 75 years and older less often with adjuvant radiotherapy after a mastectomy, and more often to employ only primary endocrine treatment for local stage disease, as compared with younger patients. According to the treatment guidelines of the institute, the study sample was divided into patients who received standard vs. non-standard treatment. The treatment of 38 women (13.1%) did not correspond with the guidelines. Of these, 84% were 75 years and older and 50% had a severe comorbidity status. Logistic regression analysis indicated that advanced age, per se, was a better indicator of the risk of not being treated according to protocol than the comorbidity status. Cox multivariate analyses demonstrated that neither the severity of the comorbidity status nor the differences in treatment between younger and older patients had a significant effect on the risk of dying from breast cancer or on the risk of developing recurrences. In this analysis, age 75 years or more proved to be a significant and independent predictor of a worse overall and disease-specific survival as compared to age between 65-74 years. PMID- 1756263 TI - Polyadenylic-polyuridylic acid plus locoregional and pelvic radiotherapy versus chemotherapy with CMF as adjuvants in operable breast cancer. A 6 1/2 year follow up analysis of a randomized trial of the French Federation of Cancer Centers (F.F.C.C.). AB - In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1-14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D. = 13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p = 0.05) in the RXAU group compared to the MCF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments. PMID- 1756264 TI - Tumor suppressor genes: a new era for molecular genetic studies of cancer. AB - Previous emphasis in cancer research has been placed on genes in which activating mutations are found in experimental systems and sometimes in human tumors, and many of these genes are the cellular homologs of retroviral oncogenes. Studies of genes whose functions are necessary for maintenance of the normal cellular state, but for which loss-of-function mutations lead to tumor development, are limited. The latter genes have been variously termed 'tumor suppressor genes', 'recessive oncogenes', and 'anti-oncogenes', and each term defines a specific aspect of their properties and may not always be applicable. The retinoblastoma (RB) gene is the first such gene to be identified, and was isolated based on its chromosome localization and on the recessive nature of the tumor phenotype. That is, both wild type RB alleles must be inactivated in a single cell for neoplastic transformation to occur, and deletions at the chromosomal locus now known to contain RB are often found in retinoblastoma cells. Candidate genes for Wilms' tumor and neurofibromatosis type I have also been identified recently, and loss of function of these genes seems to be indicated for these diseases. Allelic loss of chromosome 17p13 is frequently observed in many tumor types. The p53 gene was mapped to this chromosomal region and has been shown to be a tumor suppressor gene, and germ-line mutations of p53 recently were found to be correlated with Li Fraumeni syndrome, a syndrome characterized by multiple neoplasms. Rapid progress in studies of tumor suppressor genes points to diverse mechanisms for their functioning in the negative regulation of cell growth. A scenario depicting cell growth control by positive and negative regulators, based on new and emerging findings, is the main focus of this review. PMID- 1756265 TI - Comparing core needle to surgical biopsies in breast cancer for cell kinetic and ploidy studies. AB - The evaluability and reliability of proliferative activity (expressed as 3H thymidine labeling index, 3H-TdR LI) and ploidy determinations on core needle biopsies were compared with those obtained on surgical material from the same breast cancers. The evaluability of 3H-TdR LI on core needle biopsies was markedly lower than that on surgical material (53% vs 100%), and the association between 3H-TdR LI values in the 16 cases with both evaluable determinations was poor (rs = 0.45). Conversely, determinations of ploidy on core needle biopsy and surgical material provided superimposable results, in terms of evaluability (91% vs 100%) and reliability (rs = 0.99). Further efforts are needed to improve sampling procedures for a reliable assessment of biological markers. PMID- 1756266 TI - Sequential determination of immunocytochemical estrogen receptor and nuclear DNA content in fine needle biopsies from breast carcinoma. AB - The application of fine needle biopsy as a tool for early detection of breast cancer is becoming extensive, therefore parameters reported to be associated with prognosis should be standardized in this material. We propose the sequential determination of estrogen receptor (ER) status and DNA ploidy on the same smear obtained from a fine needle biopsy of a breast carcinoma, since both parameters seem to reflect properties associated with tumor behaviour and biological aggressiveness. Fifty fine-needle biopsies were investigated for presence of ER by the monoclonal antibody D75 followed by DNA content quantification using Feulgen-DNA cytophotometry. Overall, 66% of the tumors showed immunoreactivity for ER and 66% were classified as aneuploid. Forty-one percent of the aneuploid tumors were negative for ER, while only 7% of the diploid tumors showed no immunoreaction (p less than 0.05). The significant association between absence of immunocytochemical ER and DNA aneuploidy on the same fine-needle smear is consistent with data obtained through other methods previously reported using much larger tissue samples. PMID- 1756267 TI - MRI appearance of multiple papilloma of the breast. AB - Magnetic resonance imaging (MRI) is capable of providing a different diagnostic perspective in the evaluation of breast lesions. Its application in a single patient with multiple papilloma of the breast is described. MRI convincingly demonstrated the multicentric nature of the disease and helped to select a proper treatment plan. This report makes it clear that MRI could serve as an adjunct to mammography and sonography in selected cases. PMID- 1756268 TI - Angiosarcoma of the skin overlying an irradiated breast. AB - A case of angiosarcoma of the breast which developed six and a half years after treatment for carcinoma of the same breast is reported. As a result of radiotherapy the breast manifested signs of chronic lymphedema prior to development of angiosarcoma. Although the aetiology in this case is uncertain, there was a past history of childhood naevus regressing spontaneously. Angiosarcoma is a well known complication following radiotherapy and lymphedema, and is likely to be seen more frequently as conservation treatment is used more commonly for patients with early breast cancer. PMID- 1756269 TI - 65 and 47 kDa forms of estrogen receptor in human breast cancer: relation with estrogen responsiveness. AB - In breast cancer nearly 40% of estrogen receptor (ER) positive patients do not respond to hormone therapy. As several species of ER have been described, we examined 41 breast cancers for: (1) the presence of ER and progesterone receptor (PR); (2) the molecular weight (Mr) of ER; (3) estrogen responsiveness, appreciated by the ability of a piece of tumor transplanted in nude mice to show an estrogen-induced protein synthesis (PR synthesis). We found that there are: two species of ER with different Mr (65 and 47 kDa), and three species of tumors (36% containing the highest form of ER alone, 49% bearing the two components in variable amounts, and 15% bearing only the minor species). Eleven of these 41 tumors could be assayed for PR synthesis induction, showing that estrogen responsiveness is correlated with the major component. Due to the limited number of samples (11) the data are preliminary, but they strongly suggest that the different forms of ER could exist in the living cell with different functional abilities. PMID- 1756270 TI - Incidence of an estrogen receptor polymorphism in breast cancer patients. AB - We previously identified a polymorphism in the human estrogen receptor (ER) gene, within the coding region for the protein's amino terminal B-domain. In estrogen receptor-positive (ER+) breast tumors, the variant allele was preferentially associated with lower levels of ER, and was clinically correlated with frequent spontaneous abortions. DNA sequencing revealed a point mutation that changes codon 86 from Ala to Val and a silent mutation in codon 87. Because we initially detected the variant allele by analyzing RNA, only those tissues in which the ER gene is actively expressed were suitable for genotype analysis. We now describe an assay that uses genomic DNA as the substrate for determining the ER B genotype, DNA containing the polymorphic region of the ER gene is amplified by the polymerase chain reaction, then the amplified DNA is hybridized with radiolabeled oligonucleotide probes complementary to the wild type and variant ER alleles. This method allowed us to determine the ER B genotype of women with ER+ and ER- tumors, starting with minute amounts of DNA from frozen or paraffin embedded tissues. ER B genotyping was also performed on women without breast cancer using DNA extracted from blood cells. The combined results from analyses of RNA and DNA from 300 breast cancer patients showed that 12% were heterozygotes. In the ER+ group (n = 183), 11.5% carried the variant gene compared to 12.8% in the ER-negative group (n = 117) (chi 2 = 0.11; df = 1; p greater than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756271 TI - A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial. AB - 158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size. PMID- 1756272 TI - Prognostic value of total cathepsin D in breast tumors. A possible role in selection of chemoresistant patients. AB - Evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. In 1979, H. Rochefort described an induced protein with a molecular weight of 52,000 Daltons identified as procathepsin D. Total cathepsin D (TCD) (52K + 48K + 34K), expressed in pmol/mg protein, can be measured by an immunoradiometric method commercialized by Cis-Biointernational. Total cathepsin D was assayed in 413 breast cancer tumors from patients who underwent surgery between January 1, 1978, and December 31, 1985. Using a cut-off of 35 pmol/mg protein, patients with an elevated level had a significantly poorer survival than those with a low level (p = 0.03). This difference was not found for node-negative patients but was very significant for node-positive patients (p less than 0.008). The survival of node positive patients with a low total cathepsin level was not statistically different from that of node-negative patients. Analysis of the N+ subgroup of patients who did not receive adjuvant chemotherapy revealed that TCD no longer had any prognostic value, whereas it was still important for the N+ subgroup who received an adjuvant treatment. Cox multivariate analysis of prognostic value for survival placed total cathepsin D in third position, after nodal invasion and progesterone receptor status, for the entire population, and in first position before progesterone receptor status for the node-positive population. The association of a low cathepsin level and positive progesterone receptors characterized the subgroup of patients with the longest survival. TCD levels played the same role for prediction of the outcome of metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756273 TI - Progestin treatment depresses estrogen receptor but not cathepsin D levels in needle aspirates of benign breast disease. AB - We studied the effect of a progestin (lynestrenol) on estrogen receptors (ER) and cathepsin D (cath-D) levels immunochemically in successive fine needle aspirates of benign breast disease. Fibrocystic disease was the main pathology (43 out of 47 patients). Thirty-one patients were treated with 10 mg of lynestrenol daily from the fifth to the twenty-fifth day of the menstrual cycle for 1 to 3 months. Sixteen untreated patients were used as controls. Lynestrenol significantly decreased the percentage of ER stained cells. This is in agreement with the antiestrogenic effect of progestin and, for the first time, indicates that in vivo progestin may decrease the stimulatory effect of estrogens on mammary cells by decreasing their estrogen receptor content. No effect of progestin on cath-D level was found throughout the whole population. However, this level varied more between aspirates of each patient in the treated group than in the control group, suggesting heterogeneity in patient responses to progestin. Since cath-D may have a role in carcinogenesis, clinical follow-up of these patients and more detailed studies are required to determine whether this progestin-challenge test has any value for detecting high risk mastopathies and for predicting effectiveness of treatment. PMID- 1756274 TI - International Meeting on Functional Diseases of the Large Bowel. Ischia, April 29 30, 1990. PMID- 1756275 TI - Constipation: physiopathology and classification. AB - Constipation is commonly defined on the basis of the number of bowel movements in a week (greater than 3 week) or on the stool weight (less than 35 g/day) and on their consistency and expulsion capacity. A pathophysiological classification of constipation subdivides the patients into 2 groups. The first includes those patients in which a propulsion defect is prevalent (inertia coli) and the second one comprehends those in which a predominant expulsion defect is found. This second group consists of patients with myogenic, neurogenic or mechanical disorders. Moreover, we can consider in this group those patients with irritable bowel syndrome (IBS) who show a reduction of rectal compliance and those who produce "inappropriate stools". Finally, in this group we can find those patients having the so-called faecal impaction, that is an abnormality of either sensitivity or stimulus to defecate frequently observed in the elderly and in children. PMID- 1756276 TI - Prolonged manometric investigation of the colon in research on chronic constipation. AB - We studied the whole colonic motility for 24 hours in controls and in constipated patients. In the patient group we found a significant reduction in the colonic mass movements (6.1 +/- 0.9 vs 2.6 +/- 0.7 controls vs patients, respectively). The constipated patients showed a reduction of the colonic motor activity after the ingestion of a standard meal. Moreover, they showed, compared with controls, a significant reduction of postprandial mass movements. On the other hand we were not able to find the so-called rectal motor complex described by others. In conclusion, we believe that prolonged colonic manometry would become an important step when evaluating the pathophysiology of constipated patients, particularly of those not responding to standard treatment. PMID- 1756277 TI - Alteration of recto-anal motility in chronic idiopathic constipation. AB - We studied anorectal function in 10 controls and 13 constipated patients (chronic idiopathic constipation, outlet obstruction and inertia coli). We did not find any difference among the 3 groups as regards the internal anal sphincter (IAS) basal tone, the recto-anal inhibitory reflex (RAIR) and the maximal voluntary contraction, whereas some significant differences were observed in the sensitivity threshold. In fact, we observed that all patient groups required larger volumes in order to perceive the minimum sensation. Moreover, the patients with distal obstruction showed higher threshold for a permanent defecation stimulus. The reduction of rectal sensitivity in these patients was confirmed by the infusion of 1500 cc of saline solution. On the basis of our experience constipated patients are characterized by both normal IAS tone, RAIR appearance, squeezing capacity, and lower rectal sensitivity. PMID- 1756278 TI - The physiology of colonic motor activity. PMID- 1756279 TI - Functional radiology of the ano-rectal region. AB - Chronic constipation is probably the most common symptom resulting in a referral of patients for a dynamic radiologic investigation of the GI tract. The primary usefulness of defecography in chronic constipation is to provide details about the dynamic phenomenon of evacuation which cannot be elicited by any other medical technique. It is employed to demonstrate or rule out the presence of an anatomical deformity (prolapse, rectocele, intussusception) and/or a localized dysfunction (outlet obstruction, rectal inertia) of the distal GI tract. Defecography can distinguish between a grossly obstructed pattern and an overtly normal one, but a definitive diagnosis is made by manometry and electromyographic studies. On the other hand, it should be noted that a failure to show abnormalities by defecography does not necessarily imply a normal anorectal function. A better understanding of anorectal physiology is expected in the future from combined video-pressure studies, which will provide the exact timing between the pressure drop and barium passage through the distal colon. PMID- 1756280 TI - Pathogenesis of irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is defined as chronic-recurrent abdominal pain in absence of organic lesions. The crucial pathogenetic point is to establish whether pain is related to enhanced sensitivity of the patient or to an abnormal peripheral stimulus originating from the bowel. We can subdivide the patients with abdominal pain into two main groups: the first comprehends those patients with an abnormal response to a normal stimulus (i.e. an enhanced motor response to a meal) (irritable bowel syndrome) and second those patients who have a normal response to an abnormal stimulus (i.e. alimentary factors, laxatives, bile acids) (irritated bowel syndrome). On the basis of our knowledge we can say that the pathogenesis of IBS is complex and not yet completely defined. The crucial point is represented by our capability to discriminate between the "irritable" and "irritated" colon. PMID- 1756281 TI - Is the irritable bowel really irritable? AB - We studied 5 healthy volunteers and 9 patients with irritable bowel syndrome (IBS) during infusion of the colon with saline solution, bile acids, fatty acids and balloon distension. Our results show that the pain threshold was significantly (p less than 0.001) higher in controls than in IBS patients. Bile acids and fatty acids brought on the habitual pain in 5/7 and 7/8 patients respectively, while they did not have any effect in the control group. On the basis of our data we can conclude that the IBS patients are more sensitive to colonic distension and perfusions, thus suggesting a non-specific irritability of the colon which could be a characteristic of these patients. PMID- 1756282 TI - The irritable bowel syndrome: diagnostic strategies. AB - The irritable bowel syndrome (IBS) is characterized by abdominal pain, abdominal distension and altered bowel habits. The diagnosis is usually made by excluding other diseases. The diagnosis of IBS must be based on a) medical history (i.e. symptoms, bowel habits, normal physical examination, absence of intestinal infections or parasites) b) physiopathological evaluation (hyperactivity of the distal colon, hypersensitivity to stimuli, stress), and c) physiological evaluation of the patient. The diagnosis of IBS can be supposed in patients with typical symptoms in the absence of other diseases that were excluded by complementary examinations. PMID- 1756283 TI - Colonic sensitive-motor alterations in the irritable bowel syndrome. AB - The pathogenetic factors involved in the genesis of the irritable bowel syndrome (IBS) has not been fully explained yet. The abnormalities observed in these patients are a hypersensitivity to distension and an amplification of painful sensations. The motor activity of sigmoid colon shows an increased motility index in IBS patients with constipation and a low motility index in those with diarrhea. An hypercaloric meal induces a hypermotility in these patients. In our experience rectal distension evokes abdominal pain in 78% of cases at volumes of 100ml (less than than controls and constipated patients). The perfusion of rectum induces continuous abdominal pain in 89% of IBS patients. We can say that the motility of the whole colon over prolonged periods of time may represent an important progress in understanding the motor function in these patients. PMID- 1756284 TI - Epidemiological and sociological impact of colonic functional disorders. PMID- 1756285 TI - Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy. AB - Seventy-two patients complaining of abdominal pain were studied in a double blind trial with otilonium bromide (OB) (40 mg tid or placebo). In our patients we performed, before and after the treatment, a clinical evaluation (symptom variations) and functional studies (sigmoid manometry during bowel distension). As regards clinical parameters, otilonium bromide significantly reduced abdominal pain and bloating and significantly increased (p less than 0.02) the pain threshold. However the comparison with the placebo group did not show any difference between the two groups. Sigmoid motility during distension was significantly reduced (p less than 0.05) in OB group, whereas it did not change in the placebo group. We can conclude that, in irritable bowel syndrome (IBS) patients, OB is able to improve symptoms and to reduce stimulated motor activity of the sigmoid. PMID- 1756286 TI - A comparison of the action of otilonium bromide and pinaverium bromide: study conducted under clinical control. AB - We studied 40 patients with irritable bowel syndrome (IBS) which received in a simple-blind fashion otilonium and pinaverium bromide (15 days each drug). During each 15-day period we evaluated: number of pain episodes, intensity of pain, number of bowel movements, side effects. Otilonium bromide, (OB), compared with pinaverium bromide was able to significantly (p less than 0.05) reduce the number of pain attacks, whereas no significant differences were found between the 2 groups as regards the other parameters. The occurrence of side effects was similar in the two treatment courses. We can conclude that the two types of treatment were similarly useful in IBS, although OB seems more effective than pinaverium bromide. PMID- 1756287 TI - Mass spectrometry in the study of advanced glycation processes, responsible for long-term diabetes complications. AB - Mass spectrometry has been usefully employed in the study of the products arising from in vitro and in vivo glycation of proteins. In particular, daughter-ion spectroscopy has led to an easy detection of 2-(2-furoyl)4-(5)2(furanyl)1-H imidazole in HCl-hydrolysed glycated albumen and polylysine and the method has allowed us to exclude the presence of the same molecule in in vivo glycated proteins. Parent-ion spectroscopy has been successfully employed in the identification of furoyl-containing compounds, which are possibly responsible for the results obtained with other analytical approaches. PMID- 1756288 TI - Structure determination of the antibiotic desertomycin B by fast-atom bombardment mass spectrometric techniques. PMID- 1756289 TI - Direct molecular weight determination of resin-bound oligopeptides using 252Cf plasma-desorption mass spectrometry. AB - Plasma-desorption mass spectrometry is proved to be capable of the direct molecular weight determination of totally protected resin-bound oligopeptides. The molecular weight measured is the molecular weight of the fully protected oligopeptide including the molecular weight of the linker, which connects the oligopeptide and the polystyrene resin. This method makes it possible to check the success of (a step in) the synthesis of a peptide before its deprotection or cleaving from the resin. This can make it a strong tool in the analysis of resin bound oligopeptides. PMID- 1756290 TI - Mycobacterium tuberculosis transmission in a health clinic. AB - Between January 1 and June 30, 1988, 30 (39.5%) of 76 staff members tested at a health clinic in Florida had positive tuberculin skin test reactions. This case control study showed that people whose skin test converted were more likely than those whose skin test did not convert to have been present while patients were being treated with aerosolized pentamidine (odds ratio = 15.0; 95% confidence interval = 1.4 - 730.0) and to have worked on the first floor of the clinic (odds ratio = 9.3; 95% confidence interval = 1.1 - 420). The clinic building was poorly ventilated, and aerosolized pentamidine treatments were given in a room from which the air tended to flow into the hallway. Aerosolized pentamidine should be administered in a well-ventilated area from which the air is exhausted directly outside. All persons who are given such treatments should first be screened for tuberculosis. Use of trade names is for identification only and does not constitute endorsement by the Public Health Services or the U.S. Department of Health and Human Services. PMID- 1756291 TI - Nosocomial tuberculosis in the AIDS era: strategies for interrupting transmission in developed countries. AB - In developed countries where tuberculosis is increasing in association with HIV infection, nosocomial transmission among patients and from patients to health care workers is being increasingly reported. Nosocomial tuberculosis among HIV infected patients is difficult to prevent by conventional control measures because the clinical presentation of the disease may be atypical and confused with other respiratory infections, because the tuberculin skin test is less reliable, because cough generating procedures may increase the probability of transmission, because HIV-infected patients may progress rapidly from infection to disease, and because the organisms are increasingly drug resistant, making preventive therapy difficult. Substandard ventilation and the recirculation of air in many contemporary buildings has also been implicated in widespread nosocomial transmission. Source control through isolation and effective treatment of known or suspected cases remains the most effective strategy for preventing transmission. Dilution of infectious droplet nuclei through ventilation with outside air is important, but incompletely protective. Like ventilation with outside air, filtration of recirculated air may reduce the chance of infection by dilution, but it is expensive. Traditional surgical masks offer the wearer little or no protection. Finally, ultraviolet air disinfection may augment ventilation by inactivating organisms in the upper room air, or in ventilation ducts. PMID- 1756292 TI - Chronic airways obstruction leading to chronic hypoxemic respiratory failure: an estimate of the size and trend of the problem in Canada. AB - Chronic airways obstruction is a common cause of morbidity and mortality in Canada. It may progress to hypoxic respiratory failure and then to death. Only a few studies of the prevalence of chronic airways obstruction have been reported from Canada, but a number of studies have been reported from the United States and the United Kingdom, countries with similar socioeconomic conditions and ethnic compositions to those in Canada. The prevalence of chronic airflow limitation in these studies averages 9.3%. In each study, tobacco smoke exposure is the most prominent etiologic agent. Other contributing factors identified in the studies are air pollution, occupational exposure, respiratory infections and childhood respiratory illness. Endogenous modifiers of these risk factors demonstrated in the published studies include age, elevated peripheral blood leukocyte count and familial factors. Although epidemiologic studies have been able to identify the prevalence of functional impairment associated with chronic airways obstruction, risk factors associated with its development and modifiers of these risk factors, it is not possible to determine the prevalence of severe chronic airways obstruction resulting in hypoxemic respiratory failure. An estimate of this prevalence has been calculated based on certain assumptions. It was assumed that patients dying of chronic airways obstruction were likely, in a high proportion of cases, to have hypoxemic respiratory failure. It has been demonstrated that only one-half of all patients dying of chronic airways obstruction are correctly designated on death certificates. It was assumed, conservatively, that the median survival of patients with hypoxemic respiratory failure is two years. From these assumptions, it was estimated that the prevalence of hypoxemic respiratory failure in 1986 in Canada was 100 per 100,000 population. This is higher than the present rate of oxygen therapy, indicating that some patients currently eligible for this treatment may not be receiving it. PMID- 1756293 TI - Three decades of tuberculosis in Singapore. AB - Tuberculosis (TB) mortality for the period 1955-1959 to 1985-1989 declined 87% from 72 to 9 per 100,000 in males, and 90% from 31 to 3 per 100,000 in females. The mean annual rate of decline of mortality was 6.8%. Older persons had a lower 4.2-5.2% decline annually compared to 14.1-16.0% in the 0-4 year age group. The incidence of TB declined 80% from 438 to 88 per 100,000 in males, and 71% from 152 to 43 per 100,000 in females over the period 1960-64 to 1985-89. The mean annual rate of decline in incidence was 5.9%. The lowest decline was observed in the children below 15 years (2.8-3.2%) and elderly persons 65 years and above (2.3-5.5%). Birth cohorts of 1945-49 and earlier had progressively higher mortality risks, but declining morbidity risks as they advanced with age. Singapore has overcome the early phase of the TB epidemic as evidenced by its relatively low rates among children and females and the low rates of extra pulmonary TB and meningitis. The high incidence rates in old people are the residue of even higher rates experienced by this cohort of persons who experienced higher risks of infection in their early lives. At the prevailing rates of decline under the present conditions and control measures, TB will not be eliminated in Singapore over the next 50 years. PMID- 1756294 TI - Regulation of the human cellular immune response to Mycobacterium tuberculosis. The mechanism of selective depression of the response to PPD. AB - After infection with M. tuberculosis, about 5% of individuals develop progressive tuberculosis during the following two years and an additional 5% delayed reactivation. The genetic and acquired factors which place individuals at risk of tuberculosis are partly defined; however, the connection of the susceptibility to the host immune response is much less clear. Recent studies have examined the basis for the immunosuppression that is a concomitant of tuberculosis. Direct stimulation of monocytes primed during the course of tuberculous infection by mycobacterial peptides appears to be responsible for suppression of PPD-induced responses. Increased expression and release of interleukin-2 receptors and transforming growth-factor beta are associated with and may contribute to such suppression by monocytes. Additional studies have addressed the generation of immunity or immunosuppression. Ingestion of live M. tuberculosis by monocytes leads to selective expansion of gamma-delta T cells as opposed to CD4 lymphocytes. This may be relevant to the innate response to infection with M. tuberculosis as well as immunoregulatory circuits. Increased understanding of the basis for immunosuppression is of intrinsic interest as regards regulation of specific pathways of immune reactivity in an infectious disease of humans and may provide some insight into factors predisposing to tuberculosis. PMID- 1756295 TI - Bulletin of the International Union Against Tuberculosis and Lung Disease. Introduction. PMID- 1756296 TI - Worldwide trends in asthma morbidity and mortality. PMID- 1756297 TI - Worldwide trends in asthma morbidity and mortality. Explanation of trends. AB - The aim of this paper is to outline, in the light of present understanding of the disease, some of the likely causes for the increasing prevalence and mortality associated with asthma in different communities in the world. It seems important both to understand the causes of asthma and to taking action to reverse the trends. There is an increasing sense of urgency in addressing the problems of morbidity and mortality caused by asthma. In this regard the respiratory community is a long way behind the cardiovascular community who have been documenting the risk factors for vascular disease for many years. In the absence of a reliable definition of asthma, it is difficult to make definite statements about trends in its prevalence, morbidity and mortality. Nevertheless, as already summarised, asthma appears to be an increasing problem. the trend towards increasing deaths in some countries is particularly worrying. The mortality data are most accurate for the 5 to 34 year olds and this paper is confined to reviewing data from this age group. PMID- 1756298 TI - Prevalence of asthma in a region of Algeria. AB - In 1984-85 an epidemiological survey on asthma was carried out on a representative population sample in the "Daira de Cheraga" region in Algeria. It had two objectives: to estimate the prevalence of asthma and to describe its epidemiological pattern. The study was divided into two parts: the first was a household survey based on a questionnaire and the second, another interview at hospital, with clinical examination and pulmonary function tests with pharmacodynamic tests. The cumulative prevalence of respiratory symptoms was 2.38%. The cumulative prevalence of asthma was 1.34% and the annual prevalence 1.21%. Asthma was more prevalent in boys than girls aged under 20 years (sex ratio = 2.66) with an equal proportion after age 20 years. Asthma most often occurred in childhood in males and at an adult age in females. In 40% of cases there were family antecedents of asthma. It is impossible to extrapolate these results to the entire country and the existence of regional disparities pleads in favour of further research in this field. PMID- 1756299 TI - Determinants of airborne infection. PMID- 1756300 TI - High dose-short duration ribavirin aerosol treatment--a review. AB - A high-dose, short-duration treatment with ribavirin aerosol consisting of a three-fold increase in concentration of drug (60 mg versus 20 mg of ribavirin per mL in the liquid reservoir of the generator administered for about one-third the time of the standard treatment) was as effective as the standard dosage in the treatment of experimental influenza A and B infections in mice and in the treatment of experimental respiratory syncytial virus infection in cotton rats. Despite some minor pulmonary intolerance, it was considered to be suitable for use in treatment of patients with severe chronic pulmonary disease, and it was well-tolerated and apparently effective in the treatment (by face mask and endotracheal tube) of infants with bronchiolitis principally caused by respiratory syncytial virus infection. Pharmacokinetic studies in mice revealed very high concentrations of drug in the lungs, about triple the level with the standard dose, with similar blood and brain concentrations. Ribavirin concentrations were similarly high in respiratory secretions of infants given the triple dose. PMID- 1756301 TI - Some applications of cryosubstitution in ultrastructural studies of the cell nucleus. AB - Cryofixation followed by cryosubstitution, without the use of any chemical fixatives, was carried out on cultured mouse P815 cells. The principal aim of our work, which was to show that these techniques provide excellent morphological preservation of cellular and in particular nuclear components, was demonstrated. All nuclear structural components, nucleolar or nucleoplasmic, were clearly revealed using this technology. The cells were cryofixed by impact freezing onto a copper mirror cooled with liquid nitrogen or helium, cryosubstituted in acetone and embedded in either Lowicryl K11M or 1R White acrylic resin. Ultrathin sections were contrasted using either the usual uranyl acetate-lead citrate double staining, a differential staining for nuclear nucleoprotein structures, or the silver staining revealing nucleolar organizer regions. In view of the absence of conventional fixatives, the specimens prepared in this way would offer to be material of choice for ultrastructural identification of intra-nuclear antigens, especially those sensitive to conventional fixatives such as, for example, aldehydes. Advantages and differences of these techniques with regard to more conventional electron microscopic procedures are discussed. PMID- 1756302 TI - Cytochemical distinction of various nucleolar components in insect cells. AB - The fine structure of the insect Sf9 cell nucleolus has been investigated by means of different cytochemical and immunocytochemical techniques at the electron microscope level. Apart from a few perinucleolar condensed chromatin clumps, the insect cell nucleolus comprises two compartments. The first of these consists of a roundish compact zone formed of fibrillar material. The other is composed of fibrillar and granular structures organized into a network separated by interstitial spaces. But, unlike mammalian cell nucleoli, any fibrillar center has been observed in the Sf9 cell nucleolus, even after actinomycin D treatment. We also show that the compact fibrillar zone of Sf9 cell nucleoli contains silver stainable material and DNA. In actinomycin D-treated cells, a preferential contact of this compact fibrillar zone with condensed chromatin has been visualized. Finally, silver-stainable material has been found to persist throughout the whole mitosis. These results suggest that the compact fibrillar zone at the insect Sf9 cell nucleolus should, at least partly, correspond to the fibrillar center of mammalian cell nucleoli. PMID- 1756303 TI - Structure of the basement membrane of corneal epithelium: quick-freeze, deep-etch comparative study of networks deposited in culture and during development. AB - The basement membranes elaborated by corneal epithelium in the chick embryo and in culture conditions have been studied by quick-freezing and deep-etching methods. Electron microscope observations of en face unidirectional platinum shadow castings revealed a polygonal network comparable to the type IV collagen network described in human amniotic basement membrane and EHS mouse tumor matrix. The material deposited in culture contained type type IV collagen, as demonstrated by immunofluorescence labeling using anti-type IV collagen antibodies and formed delicate networks. Fine filaments and granules composing this network were interpreted respectively as linear and globular NC1 domains of the type IV collagen molecule. These loose networks were considered as first steps in basement membrane assembly. Staggered superimposition of comparable networks could lead to the dense network organization as observed for basement membranes in situ. These observations showed that the basement membrane of the chick embryo corneal epithelium is also organized in a complex polygonal framework that is preserved even when secreted in culture conditions. PMID- 1756304 TI - Fibrillar pattern of self-assembled and cell-assembled collagen: resemblance and analogy. AB - The geometrical characteristics of fibrillar organizations are studied by electron microscopy in structures obtained in vitro in cell-free assembled collagen gels, and in vivo in dermal tracts of anuran skin. We analyze several characteristics of the fibrils including the diameter, the outline, the curvature and the extrafibrillar space. We analyze also the variation of fibrillar orientation (twist) in longitudinal and transverse thin sections of these structures. The results are compared in the Discussion to determine to what extent these fibrillar patterns are similar to liquid crystalline organizations and to what extent they result from a self-assembly or a cell-assembly process. PMID- 1756305 TI - Genetic analysis of the cellularization of the Drosophila embryo. AB - The synchronous cellularization of the Drosophila embryo at the blastoderm stage provides a unique system for studying the molecular mechanisms involved in cytokinesis, using genetical and biochemical approaches. The cellularization process requires the major components of the embryonic cytoskeleton that are deposited into the egg during oogenesis. Genetical analysis indicates that it requires also the products of additional maternally-acting genes, as well as that of a limited set of zygotically-acting genes. The cellularization defective phenotypes associated with small deficiencies uncovering these latter loci reveal specific steps within this complex process. The molecular analysis of these genes will ultimately provide meaningful insights into the normal process of cellularization. Among them, the serendipity alpha gene encodes a membrane associated protein, which is exclusively accumulated during cellularization, and is required for the reorganization of the microfilaments as the onset of cellularization. PMID- 1756306 TI - Three-dimensional imaging of the mucus secretory process in the cryofixed frog respiratory epithelium. AB - Using the frog palate as a representative model of human mucociliary epithelium, we analyzed, after quick freezing fixation, the three-dimensional (3-D) respiratory mucus secretory release with high voltage (200-300 kV) transmission electron microscopy (TEM). The 3-D vision of the mucus release from the secretory cells was obtained as stereo-pairs and "bas-relief" images after analysis of stereo-pairs using an image analyzer. After standard glutaraldehyde fixation, the secretory cells showed a typical goblet shape with secretory granules heterogeneous in size and electron-density which often fuse together. On the other hand, quick-frozen secretory cells exhibited a columnar shape and their membrane-bound secretory granules contained a homogeneously dark matrix. The expanded gel mucus layer was preserved and its depth never exceeded 2 microns. When the epithelium was immersed in culture medium in presence of cholinergic agonist, a marked discharge of mucus was observed and the granules swelled at the apex of the secretory cell before being discharged in the lumen. In native cryofixed epithelium, the secretory granules exhibited a marked deformability during the process of their extrusion from the secretory cell. Clusters of secretory granules surrounded by cytoplasmic material were observed in the extracellular lumen, suggesting an apocrine-type secretion. These observations indicate that rapid cryofixation and 3-D stereoscopic imaging enable a unique opportunity to analyze, without artifact, the mucous secretory process. We speculate that, apart from the classical merocrine-type secretion mechanism, the respiratory mucus may be released, at least partly by an apocrine-type secretion. PMID- 1756307 TI - (3-Cryo) methods (cryofixation, cryosubstitution and cryoembedding) for processing of tissues for ultrastructural and immunocytochemical studies. Application to oviduct cells of laying quail. AB - Cryomethods occupy a privileged position among the procedures used for the preparation of biological samples for the various studies that may be performed in electron microscopy (ultrastructural, immunocytochemical and microanalysis in situ). In general, cryomethods are specific to one, or a maximum of 2 types of application. The (3-Cryo) methods (cryofixation, cryosubstitution without fixatives and cryoembedding in the new Lowicryl resins (K11M or HM23) are a set of methods for correlating new structural information with analytical and biochemical data. However, these 3-Cryomethods are delicate, complicated and expensive. To demonstrate that they can be performed, at least in part, with home made systems at a reasonable cost, we have carried out a structural and immunocytochemical study on the oviduct of the laying quail. We studied the localization of 2 proteins, one cytoplasmic (ovalbumin) and the other nucleolar (B-36). The results provided by the 3-Cryomethods are compared with those obtained with other immunocytochemical methods, including tissue processed by conventional chemical fixation and high or low temperature embedding, or by 2 Cryomethods (cryofixation and cryosubstitution). PMID- 1756308 TI - Assembly of nuclear pore complexes in Xenopus egg extract. PMID- 1756309 TI - Determination of ciliary polarity precedes differentiation in the epithelial cells of quail oviduct. AB - In quail oviduct epithelium, as in all metazoan and protozoan ciliated cells, cilia beat in a coordinated cycle. They are arranged in a polarized pattern oriented according to the anteroposterior axis of the oviduct and are most likely responsible for transport of the ovum and egg white proteins from the infundibulum toward the uterus. Orientation of ciliary beating is related to that of the basal bodies, indicated by the location of the lateral basal foot, which points in the direction of the active stroke of ciliary beating. This arrangement of the ciliary cortex occurs as the ultimate step in ciliogenesis and following the oviduct development. Cilia first develop in a random orientation and reorient later, simultaneously with the development of the cortical cytoskeleton. In order to know when the final orientation of basal bodies and cilia is determined in the course of oviduct development, microsurgical reversal of a segment of the immature oviduct was performed. Then, after hormone-induced development and ciliogenesis, ciliary orientation was examined in the inverted segment and in normal parts of the ciliated epithelium. In the inverted segment, orientation was reversed, as shown by a video recording of the direction of effective flow produced by beating cilia, by the three-dimensional bending forms of cilia immobilized during the beating cycle and screened by scanning electron microscopy, and by the position of basal body appendages as seen in thin sections by transmission electron microscopy. These results demonstrate that basal body and ciliary orientation are irreversibly determined prior to development by an endogenous signal present early in the cells of the immature oviduct, transmitted to daughter cells during the proliferative phase and expressed at the end of ciliogenesis. PMID- 1756310 TI - Centriole and basal body formation during ciliogenesis revisited. AB - This review is concerned with the formation during ciliogenesis of centrioles and basal bodies, primarily in epithelial multi-ciliated cells from the developing vertebrate respiratory and reproductive tracts. During ciliated cell differentiation, in these as well as in other cell types, cilium formation is preceded by the formation of centrioles assembled from precursor structures having little resemblance to the mature organelle. The origin, composition and function of the centriole precursor structures in generating large numbers of centrioles in a short period of time during ciliogenesis is discussed. This review also focuses on the biochemistry of centrioles and basal bodies and on recent experimental evidence that DNA might be associated with these structures. PMID- 1756311 TI - Expression of the nuclear protein mitotin in differentiating in vitro HL 60 cells. AB - Mitotin is a 125 kDa/pI 6.5 nuclear protein specific for proliferating cells and markedly increased prior to and during mitosis. This study presents evidence for the expression of this protein during dimethylsulfoxide (DMSO) induced differentiation of human promyelocytic leukemia HL 60 cells. The expression had been followed at two levels: as antigen, using a specific antimitotin monoclonal antibody and as mRNA, using a specific cDNA probe. The results from the immunofluorescent study show a gradual disappearance of mitotin in differentiating HL 60 cells starting from the fourth day after DMSO induction. On the other hand, the changes in the expression of mitotin mRNA were much more dramatic. This mRNA is expressed at a high level during the first three days of differentiation but shows a striking decrease after the fourth day. This correlates with the rapid changes in the number of blast cells in the differentiating HL 60 cell population. Therefore, the expression of mitotin mRNA can serve as a marker for the changes accompanying the termination of cell proliferation in differentiating cells. PMID- 1756312 TI - De novo formation of centrioles in parthenogenetically activated, diploidized rabbit embryos. AB - In rabbit oocytes activated parthenogenetically by repetitive electric pulses, centrioles develop de novo in blastocysts. Centrioles were not observed in earlier stages of development, not until the blastocoele is formed. Up to the morula stage (between 8-32 cells), a filamentous, electron-dense material develops and aggregates with a small vesicle fraction within the well developed Golgi apparatus. A spherical to ovoid electron dense mass forms, which is comparable to the deuterosome or to the blepharoplast. The quantity of the electron dense material enlarges and it seems to give rise to the centriole "generating complex". Centrioles arise in all three differentiated cell types of the blastocysts, the mural and polar trophoblasts and the embryonal cell mass at the same time. Some of the forming centrioles in parthenotes have a co-linear arrangement, as in control blastocysts. It is not yet known whether the co linearly arranged centrioles represent a maturation phase, prior to the formation of the usual diplosome, with centrioles oriented perpendicularly to each other. Nor is it known whether the forming centrioles are functioning as the polar organizer of the mitotic spindle or if they can perform any other centriolar function. PMID- 1756313 TI - Ultrastructural changes in the shape of neurons and related structures in frog sympathetic ganglia after axotomy. AB - Changes in the shape of neuronal perikarya and other ganglionic structures were observed by electron microscopy in the frog sympathetic ganglia at different times after axotomy. Degenerating and hypertrophic profiles appeared to reflect a remodelling process affecting preganglionic fibres. The shape of neuronal perikarya was modified by the formation of infoldings occupied by preganglionic fibres and/or by that of short winding dendrites often bearing a synapse. The origin of these changes is discussed. In frog sympathetic ganglia, the period of recovery after axotomy was marked by specific reactions which affected neuronal shape and preganglionic fibres, and are not known to occur in the ganglia of mammals. PMID- 1756314 TI - Subcellular distribution of clathrin in cultured hypothalamic neurons. AB - The subcellular distribution of clathrin has been examined in developing hypothalamic neurons cultured in a chemically defined medium up to synapse formation (12-13 days in vitro) and exposed, or not, to a depolarizing concentration of KCl (60 mM for 3 min) followed, or not, by a return to control KCl concentration (3 mM KCl for 3 min). Previous studies have shown that such treatments induce in synaptic boutons a rapid vesicle depletion followed by massive restoration. Using an enzyme immunoassay, we have compared the relative proportion of assembled and unassembled pools of clathrin as a function of exposure to depolarizing or repolarizing concentrations of KCl. In parallel we have localized clathrin at the electron microscopic level using immunoperoxidase. Clathrin concentration in culture is lower (0.36 vs 0.75%) and the proportion of unassembled clathrin is much higher than in the adult brain (82 vs 14%). These proportions were not affected by depolarizing or repolarizing treatments. Morphologically clathrin was exclusively detected in two neuron compartments: perikarya and synaptic boutons. In perikarya clathrin was localized as a thick coat on plasma membrane coated pits and in the Golgi zone on coated buds and vesicles, presumably located in a trans compartment. In synaptic boutons clathrin immunoreaction was found as an irregular thin rim around synaptic vesicles, whatever the polarization state of the cells, but coated vesicles were extremely rare. Taken together these findings raise the problem of the functional meaning and localization of the large unassembled pool of clathrin in such neurons and question its role in vesicular traffic in synaptic boutons. PMID- 1756315 TI - Heat shock response of Babesia divergens and identification of the hsp70 as an immunodominant early antigen during ox, gerbil and human babesiosis. AB - Using antisera (alpha-R and alpha-C7Ag) directed against the conserved Gly-Gly Met-Pro-epitope of the hsp70 family, a single antigen was identified in the human Babesia divergens Rouen 1987 isolate by Western immunoblotting and immunoprecipitation experiments. This B divergens hsp70 is highly conserved as shown by the analysis of five other geographical B divergens isolates from different hosts (human and bovine). Indirect immunofluorescence assay performed on the asexual intraerythrocytic stages showed that the hsp70 is mainly cytoplasmic and stage-independent. Heat-shock experiments, with 20 min incubation at 40 degrees C followed by a 10 to 50 min shift to 37 degrees C in the presence of [35S]-methionine, led to an increase of two hsp of 85 and 70 kDa while protein synthesis in general decreased within 10 min. Immunoprecipitations of [35S] methionine radiolabelled proteins with human, ox and gerbil antisera raised against various B divergens isolates, showed the presence of a B divergens 70 kDa protein which was demonstrated to be a hsp70 by coupling immunoblotting assays with alpha-C7Ag serum on the same immunoprecipitated material. During human babesiosis, the B divergens hsp70 appears as an early antigen during the acute phase. These results are in agreement with the use of the B divergens hsp70 as an essential valence antigen in an anti-babesiosis vaccine. PMID- 1756316 TI - Long-term repeatability of the pure-tone hearing threshold and its relation to noise exposure. AB - Audiometric repeatability is examined for a population of 356 male and female industrial employees (712 ears), sub-divided according to the amount of previous noise exposure. Re-tests were carried out after an interval averaging 13 months. After a similar interval, 150 of the subjects gave a third audiogram. Fixed frequency self-recording audiometry was employed, using common equipment and procedures throughout. Results are presented as distributions of the algebraic test-re-test differences for each frequency and for the frequency combination 1-2 3 kHz. Repeatability was best at 1 and 2 kHz and substantially poorer at 6 kHz. Cumulative distributions of the signless differences show that more than 50% of initial hearing threshold levels repeated to better than 5 dB. For all frequencies except 6 kHz the mean values of signless test-re-test differences for the various sub-groups were between 3.4 and 5.6 dB; at 6 kHz the values were between 5.8 and 7.8 dB. In the case of the three-frequency average, the mean differences were reduced to between 2.8 and 3.8 dB. A few repeats (about one in 200) stand out as clearly anomalous; these occur only in isolation and mainly at the higher frequencies. The performance of groups classified by the amount of their previous noise exposure did not differ significantly. In the case of those tested three times, the repeatability over the second inter-test interval showed at most a marginal improvement compared with the first interval. PMID- 1756317 TI - Auditory localization under conditions of unilateral fitting of different hearing aid systems. AB - The spatial localization function of hearing-impaired listeners, usually fitted bilaterally with BTE, ITE or ITC devices, was tested under conditions of unilateral fitting of each of their own hearing aids, and unilateral fitting of stock versions of each of the other types. For the BTE wearers average localization accuracy and individual variability were not greatly changed when wearing only their left ear device, compared with bilateral aided performance. In ITE wearers, unilateral fitting in either ear led to somewhat poorer performance than bilateral. In the ITC wearers unilateral fitting produced inconsistent outcomes. Both BTE and ITE wearers fared poorly when fitted unilaterally with stock forms of devices 'foreign' to them, whereas ITC wearers did not show such a contrasting outcome. A group of non-impaired listeners showed severe disruption of localization under unilateral BTE and ITC hearing aid conditions, and to a lesser extent with ITEs. Results for the hearing-impaired listeners are interpreted in terms of adaptation to different usage patterns, with BTE wearers suggested as having adapted to their own systems unilaterally as well as bilaterally. PMID- 1756318 TI - A comparison between the electrically reproduced loudness and the original loudness of speech at high levels. AB - Four words lists of a German Speech Intelligibility Test (DIN 45621) were recorded at 60 and 75 dB SPL. Both recordings were presented to 20 normally hearing subjects at 75 dB SPL via free-field equalized earphones. Discrimination in noise was significantly better in the original recording at 60 dB SPL. The better understanding may be explained by a more favourable consonant-vowel intensity ratio. Moreover, a significant increase in fundamental frequency could be demonstrated at the higher recording level. The implications for speech audiometry and hearing aids are discussed. Furthermore, it was found from loudness comparisons that both recordings were equally loud at a level of 75 dB SPL. However, significantly increased loudness was indicated in the 75 dB SPL recording by the loudness calculation procedure ISO 532 B. PMID- 1756319 TI - An evaluation of ABR audiometry for the screening and detection of hearing loss in ex-SCBU infants. AB - The study aimed to use auditory brainstem response (ABR) audiometry to test ex SCBU infants born during 1986 in West Berkshire. Two hundred and forty-three babies were tested as out-patients, thus achieving a coverage rate of 86% of the target population. Mean post-conceptional age at test was 48 weeks. Whenever possible, full ABR threshold determination was performed on both ears and the mean ABR threshold was found to be 14 dB nHL. Of those babies attending, 85% showed ABRs at less than or equal to 30 dB nHL bilaterally and the remaining 15% were referred for further assessment. Approximately two-thirds of these were recalled successfully for repeat testing. The estimated prevalence rate for bilateral sensorineural hearing impairment was 1.4% with four confirmed cases. Two additional permanent unilateral hearing losses were also detected. On the basis of recorded ABR data, sensitivity, specificity and positive predictive values were estimated for click intensities which could be used for single intensity ABR screens. It is concluded that delaying screening until the post neonatal stage is a viable alternative to screening neonates prior to discharge from the SCBU. PMID- 1756320 TI - Isochronic mapping: a preliminary report of a new technique. AB - A new technique which we have named 'isochronic mapping' is described. The conventional technique of plotting isopotential maps shows little or no contrast for far-field potentials such as the auditory brainstem response (ABR). However, by modifications to the mapping software, the latency values of a peak can be plotted and lines of equal time or isochronic maps can be produced. Data from a normal subject has been obtained for both the compound and derived ABRs and are described in detail. The data are clear but the time delays between earliest and latest projections of a peak are hard to interpret. For monaural click stimulation, wave JV of the ABR projects first to the contralateral side of the head then moves towards the stimulated ear arriving some 0.3 ms later. Possible interpretations of this finding are discussed but further experimentation is needed to develop our understanding of these data. PMID- 1756321 TI - Influence of total body irradiation on infections after autologous bone marrow transplantation. AB - Infectious complications were analysed in 50 consecutive autologous bone marrow transplant (ABMT) patients treated with high dose etoposide and melphalan, 30 of whom also received total body irradiation (TBI). Fever developed in 44 patients and bacteremia was documented in 13 (26%). Patients given TBI had increased susceptibility to bacteremia; 11 of 30 patients who received TBI had positive blood cultures, in contrast to two of the 20 who did not (p = 0.035). In addition, patients who received TBI had significantly more severe diarrhea (p = 0.037) when compared with those who received chemotherapy alone. Thirty-five patients treated with trimethoprim-sulfamethoxazole prophylaxis had a signficantly lower incidence of gram-negative bacteremia (p = 0.024). However, when those patients who received trimethoprim-sulfamethoxazole until neutrophil recovery were analysed alone, those who were also given TBI still had significantly more bacteremia (p = 0.047). Forty-seven patients with follow-up of more than 12 months are available for analysis of varicella zoster (VZV) infections. Of the 29 patients who received TBI, 11 (38%) developed VZV infections, in contrast to one of 18 patients (6%) treated with chemotherapy alone (p = 0.013). These results suggest that addition of TBI to the intensive therapy regimen for ABMT is associated with significantly more bacteremia and late VZV infections. PMID- 1756322 TI - Graft-versus-leukaemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukaemia cells. AB - Cytotoxic T lymphocyte precursor (CTLp) frequency assays were examined in patients with chronic myeloid leukaemia (CML) following bone marrow transplantation (BMT) using recipient lymphocytes or CML cells as targets in a 51Cr release cytotoxicity assay. Eighteen patients were studied; 11 received marrow from a fully HLA A, B and DR matched sibling donor, and six from matched unrelated donors or a partially matched sibling (one patient). Two of the unrelated donor transplant recipients received marrow depleted of T lymphocytes, and the remainder received unmanipulated marrow and cyclosporin with or without methotrexate as prophylaxis against graft-versus-host disease (GVHD). Donor cells tested before BMT did not generate CTL against the patients' leukaemia, but up to 9 months after BMT a low frequency of CTLp directed against the patients' CML cells (Lk-CTLp) was detected in all patients. The Lk-CTLp frequency was significantly lower than the frequency of CTLp directed against the recipients' PHA transformed pretransplant lymphocytes (Ly-CTLp) (p less than 0.05). Lk-CTLp showed MHC restricted cytotoxicity and did not demonstrate cytotoxicity in an NK assay. The Lk-CTLp frequency correlated with both GVHD severity and relapse: severe GVHD was only seen with Lk-CTLp frequencies greater than 1:400,000, while leukaemic relapse was only observed in two patients with Lk-CTLp frequencies less than 1:400,000. These results show that a low frequency of alloreactive cells of presumed donor origin with cytotoxic potential against residual leukaemia normally circulate after BMT. Their relationship with the graft-versus-leukaemia phenomenon and their cross-reaction with GVHD reacting cells remain to be determined. PMID- 1756323 TI - Intravenous interleukin-2 just after high dose BCNU and autologous bone marrow transplantation. Report of a multicentric French pilot study. AB - This multicentric pilot study was conducted in order to evaluate the feasibility of early interleukin-2 (IL2) after high dose chemotherapy requiring autologous bone marrow transplantation (ABMT). BCNU at 800 mg/m2 was followed, 3 days later, by the reinjection of the bone marrow cells. At day 4, IL2 at 18 x 10(6) i.u./m2/day was given as a continuous infusion during a minimum of 6 days (first phase of study) or for 6 more days after 1 day break (second phase of the study). Twenty patients were included. Toxicity was not negligible, with one toxic death, but IL2 therapy does not damage the haematological recovery of most patients. However, a 6-day IL2 treatment period only appears tolerable. In 18 evaluable patients, three responses were observed: one complete response (CR) of short duration in a non-Hodgkin's lymphoma, one CR (24 months +) and one partial response (PR) (6 months) in two patients with metastatic gastric adenocarcinoma. This study confirms that IL2, restricted to a 6-day treatment period, is feasible immediately after high-dose chemotherapy requiring ABMT without haematological problem in most patients. The response rate was unexpected for a pilot study and this combined therapy obviously requires further study. PMID- 1756324 TI - In vitro marrow purging in chronic myelogenous leukemia: effect of mafosfamide and recombinant granulocyte--macrophage colony-stimulating factor. AB - Clinical and experimental evidence revealing Ph1-negative hematopoietic stem cells in the majority of chronic myelogenous leukemia (CML) patients, suggests that autologous bone marrow transplantation (ABMT) may represent a therapeutic approach for these patients. It was the aim of the present study to evaluate the efficacy of the cyclophosphamide derivative mafosfamide as a marrow purging agent in a group (n = 15) of CML patients. Chemical purging was followed by a short term liquid culture phase supplemented with recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Mafosfamide (100 micrograms/ml) incubation induced a marked inhibition of progenitor cell growth, the percentages of surviving CFU-GEMM, BFU-E, and CFU-GM being 3.4, 5.4, and 4.9, respectively. At the cytogenetic level, the purging procedure failed to show any modulating effect on Ph1-negative clones in 9/15 cases. In contrast, 6/15 cases showed a significant increase in the mean (+/- SD) percentage of Ph1-negative metaphases in response to rGM-CSF (46 +/- 26, p less than or equal to 0.05), mafosfamide incubation (53 +/- 12, p less than or equal to 0.01), and the combination of mafosfamide incubation plus rGM-CSF (63 +/- 29, p less than or equal to 0.025). Immunological analysis revealed that mafosfamide incubation induced a significant enrichment of MY10 (28 +/- 9, 0.05) B73.1-positve cells (25 +/- 9, p less than or equal to 0.05). Four mafosfamide-responsive patients with CML in second chronic phase have been autografted with mafosfamide purged marrow. In all patients a Ph1 negative phase lasting 5-14 months was observed. In conclusion, it appears that (a) in a subgroup of CML patients mafosfamide purging is effective in reducing the size of the malignant clone and might induce through its cytotoxic and immune actions a modification of the balance between leukemic and normal clones, and (b) this experimental approach may be used as a screening test to select patients to undergo marrow harvest and ABMT with mafosfamide purged marrow. PMID- 1756325 TI - Autologous bone marrow transplantation as consolidation therapy for non-Hodgkin's lymphoma patients with poor prognostic features. AB - Theoretical considerations and preliminary results of clinical trials support the earlier use of autologous bone marrow transplantation (ABMT) in poor prognosis non-Hodgkin's lymphoma (NHL). A prognostic analysis of 50 patients with intermediate or high grade NHL younger than 60 years, who achieved at least one complete remission and were not treated with BMT, was performed. Patients with bulky tumor at diagnosis and/or serum LDH greater than or equal to 600 U/l do poorly with conventional chemotherapy. Twelve patients with these high-risk initial characteristics in first complete remission (CR) and six patients in second or third CR were treated with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000-1200 cGy) followed by ABMT. Overall disease-free survival was 65% at a median follow-up of 35 months. No differences were found between the first and later CR patients. The rate of toxic death was 11%. Disease-free survival after first CR was better for 1st CR ABMT patients than for a historical chemotherapy control group with similar poor prognosis features (p = 0.008). These results support the use of ABMT in selected, high-risk NHL patients in first CR. PMID- 1756326 TI - A simple, efficient washing procedure for cryopreserved human hematopoietic stem cells prior to reinfusion. AB - We describe our experience with a washing procedure used on cryopreserved, thawed bone marrow (BM) and peripheral blood stem cell (PBSC) grafts prior to autologous transplantation in 50 and 12 patients respectively. The procedure consists of a stepwise dilution with 2% human serum albumin and centrifugation performed either manually or using a blood cell processor (Cobe 2991). In vitro studies showed mean recoveries of 80.8% for BM nucleated cells and 73.9% for BM hematopoietic progenitors (CFU-GM). The corresponding recoveries for PBSC were 89.1 and 93.9%. After 4 h storage at +20 degrees C of the manipulated grafts, no significant loss of CFU-GM was observed. We conclude that the technique is simple and efficient for washing large numbers of hematopoietic stem cells. This method may avoid the clinical complications often arising with unwashed grafts. PMID- 1756327 TI - Alpha-interferon broadens the difference between surviving fractions of normal and leukemic progenitor cells in vitro by heat: its application to marrow purging. AB - Alpha-interferon (IFN) may inhibit the proliferation of human leukemic progenitor cells (L-CFU) in vitro and enhance the anti-tumor effects by heat. In this study, the combined effects of IFN and hyperthermia on the growth of L-CFU and human granulocyte-macrophage progenitors (CFU-GM) were examined to determine if this combination resulted in a greater selective killing of L-CFU than that obtained by heat treatment alone. The survival of normal CFU-GM without IFN decreased at elevated temperatures (42-44 degrees C). However, IFN added during heating (42 and 43 degrees C) appeared significantly to protect against the hyperthermic killing of CFU-GM in vitro leaving over 50% of CFU-GM surviving. The optimal dose to protect CFU-GM in vitro dropped to a rather low dose (100 U/ml). On the other hand, the addition of IFN to leukemic cell suspensions enhanced the hyperthermic killing of myeloid leukemic cell lines (HEL and KG-1) as well as a T lymphoblastic cell line (CEM) in a dose-related manner. In addition, similar results were observed in the study of L-CFU from patients with acute myelogenous leukemia. These results suggest that IFN can be used to broaden the difference between surviving fractions of CFU-GM and L-CFU by heat. Thus, this combination could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous remission marrow graft before autologous bone marrow transplantation. PMID- 1756328 TI - Long-term complete remission after allogeneic bone marrow transplantation in multiple myeloma. AB - We report a case of IgG lambda type multiple myeloma treated by allogeneic bone marrow transplantation. After transplant the monoclonal protein persisted for 2 years with no other sign of disease. Thereafter the monoclonal protein was no longer detectable and the patient was considered to be in complete remission for the next 4 years. PMID- 1756329 TI - Unusually long survival after autografting in second partial remission of translocation t(4;11) acute infant leukemia. AB - About 70% of children with acute lymphoblastic leukemia may be cured by conventional chemotherapy. The prognosis is considerably worse in infant leukemia with a translocation t(4;11). We report an infant with a diagnosis of cytochemically undifferentiated acute hybrid leukemia (pre pre B-ALL coexpressing one myelomonocytic marker) and t(4;11). Initial clinical presentation and the course of the disease were typical for t(4;11) acute leukemia. After an early hematologic relapse intensive chemotherapy resulted only in a second partial remission 7 months after initial diagnosis. Subsequent bone marrow transplantation with 16 mg/kg busulfan and 200 mg/kg cyclophosphamide followed by the infusion of autologous purged bone marrow resulted in a continuous second remission which has lasted 46 months so far. PMID- 1756330 TI - Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation. AB - Acute inflammatory demyelinating polyneuropathy (AIDP) appeared in two patients following allogeneic bone marrow transplantation (BMT). In one transplanted patient (but not in the donor) T cells were sensitized against peripheral nervous system myelin. This could reflect a change in the T cell repertoire in a different milieu. In this context, AIDP might be part of graft-versus-host disease or another associated autoimmune disorder following BMT. PMID- 1756331 TI - Presumptive invasive Chrysosporium infection in a bone marrow transplant recipient. AB - Chrysosporium species caused an invasive infection in an 18-year-old patient following allogeneic sibling bone marrow transplant for T lineage acute lymphoblastic leukemia. This infection began as a facial swelling and extended into the central nervous system. Fungal disease spread rapidly despite antifungal agents. An autopsy showed fungal involvement of brain, lungs, liver and kidneys. PMID- 1756332 TI - Cerebral infarction associated with protein C deficiency following allogeneic bone marrow transplantation. AB - Hypercoagulable states associated with deficiencies in circulating anticoagulant protein C occur after chemotherapy for a variety of malignant diseases. Protein C deficiency also occurs following bone marrow transplantation (BMT) and may be responsible for a variety of transplantation-associated complications. We report the case of a child who suffered a stroke associated with low protein C antigen and activity occurring 11 months after allogeneic BMT. Protein C levels recovered spontaneously by 18 months after BMT. We speculate that the protein C deficiency and and resultant hypercoagulable state led to the stroke, and the deficiency of this anticoagulant was a sequela of the transplant. PMID- 1756333 TI - Poor circulating CFU-GM harvest and slow hematologic reconstitution in a patient with chronic granulocytic leukemia undergoing autologous transplantation. PMID- 1756334 TI - Endobronchial aspergillosis in marrow transplant patients. PMID- 1756335 TI - Computerised tomography in Alzheimer's disease. Methods of scan analysis, comparison with normal controls, and clinical/radiological associations. AB - One hundred and thirty-eight patients satisfying NINCDS/ADRDA criteria for Alzheimer's disease (AD) and 36 normal controls underwent cranial CT. A comparison of methods of scan analysis showed good agreement between computer assisted methods and visual ratings and planimetry. The CT scans of controls differed significantly from patients and a discriminant analysis, based on all CT measures, predicted group membership (control or patient) in 81% of cases. Within the AD group, cortical atrophy correlated with age and duration of illness. Global tests of cognitive function correlated significantly with both cortical atrophy and ventricular size. Subjects who died in a three-year follow-up had more atrophy and larger third ventricles than survivors, but this effect was due entirely to increased age. PMID- 1756336 TI - 'Schizoid' personality in childhood and adult life. I: The vagaries of diagnostic labelling. AB - The literature is reviewed on children variously described as having 'schizoid' personality disorders, Asperger's syndrome, and schizotypal personality disorders, with the aim of clarifying the nature of these clinical syndromes, and in particular the features of those children whose follow-up characteristics are described in the following two papers. PMID- 1756337 TI - 'Schizoid' personality in childhood and adult life. II: Adult adjustment and the continuity with schizotypal personality disorder. AB - In a controlled follow-up study into adulthood of 32 children diagnosed 'schizoid', three-quarters fulfilled DSM-III criteria for schizotypal personality disorder and two developed schizophrenia. Overall their psychosocial adjustment was somewhat, but not markedly, worse than that of other attenders at a child psychiatry clinic, although as a group they remained more solitary, lacking in empathy, oversensitive, with odd styles of communicating, and often with circumscribed interests. PMID- 1756338 TI - 'Schizoid' personality in childhood and adult life. III: The childhood picture. AB - The childhood case records of 32 'schizoid' children and 32 matched controls were analysed. 'Schizoid' children were characterised by solitariness, unusual fantasies, special interests, and specific developmental delays, especially of language-related skills. They were of average or above-average IQ, and half presented with other, common, child psychiatric syndromes. It is important to distinguish 'schizoid' children from children with reactive psychiatric disorders. PMID- 1756339 TI - Coherence on electroencephalography and aberrant functional organisation of the brain in schizophrenic patients during activation tasks. AB - Thirty schizophrenic patients (20 medicated, 10 off medication) were compared with 30 normal control subjects matched for age, sex, handedness, and intelligence. During the performance of left-hemisphere cognitive activation tasks, normal subjects had significantly increased EEG alpha coherence in areas related to left focal frontal sites, with decreases in temporal and posterior areas. Schizophrenic patients did not show the same degree of focal activation of left frontal areas. During the performance of right-hemisphere cognitive activation tasks, normal subjects and schizophrenic patients had similar patterns of right posterior increases in alpha coherence. Discriminant analyses were able to classify 81.4% of all subjects correctly. It is suggested that the findings indicate an aberrant functional organisation of the brain in schizophrenia, particularly affecting the left hemisphere. PMID- 1756340 TI - Cross-cultural feasibility, reliability and sources of variance of the Composite International Diagnostic Interview (CIDI). The Multicentre WHO/ADAMHA Field Trials. AB - The CIDI is a fully standardised diagnostic interview designed for assessing mental disorders based on the definitions and criteria of ICD-10 and DSM-III-R. Field trials with the CIDI have been conducted in 18 centres around the world, to test the feasibility and reliability of the CIDI in different cultures and settings, as well as to test the inter-rater agreement for the different types of questions used. Of 590 subjects interviewed across all sites and rated by an interviewer and observer, 575 were eligible for analysis. The CIDI was judged to be acceptable for most subjects and was appropriate for use in different kinds of settings. Many subjects fulfilled criteria for more than one diagnosis (lifetime and six-month). The most frequent lifetime disorders were generalised anxiety, major depression, tobacco use disorders, and agoraphobia. Percentage agreements for all diagnoses were above 90% and the kappa values were all highly significant. No significant numbers of diagnostic disconcordances were found with lifetime, six-month, and four-week time frames. PMID- 1756341 TI - The CIDI-core substance abuse and dependence questions: cross-cultural and nosological issues. The WHO/ADAMHA Field Trial. AB - The CIDI is a fully standardised, structured interview for the assessment of psychiatric disorders according to DSM-III-R and proposed ICD-10 criteria. The development of this interview has been the collaborative effort of researchers from 18 sites around the world. In a field trial to test the cross-cultural acceptability and reliability of the questions, there was found to be high acceptance and excellent reliability for the substance use questions, problems with the lengthy alcohol section, and difficulties translating relevant substance use concepts into different languages. There is therefore room for further improvement in the substance-related questions. There proved to be differences between ICD-10 and DSM-III-R regarding substance abuse and dependence disorders. PMID- 1756342 TI - Prognosis of depression in the elderly. AB - Fifty-six consecutively admitted elderly (65 and over) patients with depression were assessed on mental, physical and social states. They were followed up and assessed at home one year later. A group of 24 depressed in-patients aged under 65 years admitted to the same ward during the same period was also assessed. Outcome was different for the two groups, with 68% of the elderly 'well' at one year, against 50% of the younger group. The younger group were more likely to have 'poor' outcome (41%) than the elderly (16%). However, there were more deaths than expected, particularly in the elderly. These findings differ from some previous studies, and indicate an excellent prognosis for depression in the elderly. Outcome in younger patients is less good. PMID- 1756343 TI - Sexual abuse as a factor in eating disorders. AB - Clinicians have reported a link between sexual abuse and eating disorders, but research evidence to date has been equivocal in supporting that link. This study presents data on reported sexual abuse from 67 anorexic and bulimic patients. Bulimics were substantially more likely to report a history of unwanted sexual experience than anorexics. The method used (clinical interview v. questionnaire) did not affect reported rates of abuse. It is suggested that sexual abuse per se may not cause eating disorders, but may determine the nature of those disorders when they have been prompted by other factors. PMID- 1756344 TI - Placebo and analgesic nitrous oxide for treatment of the alcohol withdrawal state. AB - We present evidence that analgesic (as distinct from anaesthetic) nitrous oxide is superior to placebo in the treatment of the alcohol withdrawal state. 'Carbogen' as a placebo is as effective as oxygen or medical air. However, placebo alone offers a means of treating the alcohol withdrawal state with a minimum of pharmacological intervention. Analgesic nitrous oxide for those not responding to placebo is a very rapid, effective, and extremely safe treatment which also reduces the use of highly addictive sedative pharmacological agents. This therapy also provides a rapid method of screening those patients requiring intensive monitoring and treatment in hospital from those who might benefit from out-patient therapy alone. PMID- 1756345 TI - Construction of an index for predicting suicide attempts in depressed adolescents. AB - A group of 48 adolescents who recently attempted suicide and 66 depressed adolescents were compared on sociodemographic, behavioural, psychological and relational variables. The variables which proved significant were used in different combinations in stepwise logistic regression analyses, resulting in seven variables which served as the content of an index of risk. The sensitivity of the index was 90% and the specificity 83%. At one-year follow-up the occurrence of a suicide attempt correlated with score on the instrument. PMID- 1756346 TI - Maternal mental health in a squatter settlement in Rio de Janeiro. AB - The literature on household-based measures of mental health in developing countries is limited. Much emphasis is currently placed on the physical well being of mothers in relation to child care, yet their mental well-being receives little attention. The present study measures maternal mental health in the largest squatter settlement of Rio de Janeiro, Brazil. The proportion of mothers who were probable cases of mental ill-health was 36%. PMID- 1756347 TI - Dhat syndrome--a useful diagnostic entity in Indian culture. AB - In a prospective study of 144 consecutive male patients with psychosexual disorders, comprising 93 with Dhat syndrome with or without impotence or premature ejaculation, 21 with premature ejaculation, and 30 suffering only impotence, the commonest associated psychiatric illness was neurotic depression (39%) followed by anxiety neurosis (21%), while 31% did not receive a psychiatric diagnosis. The common presenting a symptoms of Dhat syndrome were weakness (71%), fatigue (69%), palpitations (69%), and sleeplessness (62%). After random allocation into groups, four types of treatment were given: an anti-anxiety drug, an antidepressant, a placebo, or counselling. The best response was seen with the anti-anxiety and antidepressant drugs. Twenty-one patients dropped out of treatment; 15 of whom were from the counselling group. PMID- 1756348 TI - Against pathology. The new psychiatry and its critics. AB - The notion of 'pathology' presumes an experiential and socially embedded frame of reference which is at variance with some recent attempts to understand the procedures and subject matter of psychiatry. Psychiatric theories remain bound by individual and historical contingencies whose compelling urgency obfuscates the inter-relationship of phenomenon, social context, response, and explanatory model. PMID- 1756349 TI - Role of general practitioners in care of long-term mentally ill patients. AB - "OBJECTIVE--To assess general practitioners' involvement with long term mentally ill patients and attitudes towards their care. DESIGN--Postal questionnaire survey. SETTING--General practices in South West Thames region. SUBJECTS--507 general practitioners, 369 (73%) of whom returned the questionnaire. MAIN OUTCOME MEASURES--The number of adult long term mentally ill patients whom general practitioners estimate they have on their lists and general practitioners' willingness to take responsibility for them. RESULTS--110 respondents had noticed an effect of the discharge of adult long term mentally ill patients on their practices. Most (225) respondents estimated that they had 10 or fewer such patients each on their lists. Having higher numbers was significantly associated with practising in Greater London or within three miles of a large mental hospital and having contact with a psychiatrist visiting the practice. 333 general practitioners would agree to share the care of long term mentally ill patients with the psychiatrist by taking responsibility for the patients' physical problems. Only 59 would agree to act as a key worker, 308 preferring the community psychiatric nurse to do it. Only nine had specific practice policies for looking after long term mentally ill patients and 287 agreed that such patients often come to their general practitioner's attention only when there is a crisis. CONCLUSIONS--The uneven distribution of long term mentally ill patients suggests that community psychiatric resources might be better targeted at those practices with higher numbers of such patients. Most general practitioners seem to be receptive to a shared care plan where the consultant takes responsibility for monitoring psychiatric health with the community nurse as key worker. The lack of practice policies for reviewing the care of long term mentally ill patients must limit general practitioners' ability to prevent crises developing in their care." PMID- 1756350 TI - Suicide among immigrant psychiatric patients in Canada. AB - Ninety-four Canadian-born psychiatric patients who committed suicide were compared with 23 foreign-born patients committing suicide in Canada. East Europeans were over-represented, and significant differences were found in the age distribution, stress, level of education, social isolation, and methods of suicide. Most foreign-born patients had come to Canada for family or economic reasons but were unemployed, with poor social integration. Employment, housing, education, social integration and a support network seem to be important in preventing these deaths. Cultural evaluation of the patient and early intervention is recommended. PMID- 1756351 TI - Mania secondary to thyrotoxicosis. PMID- 1756352 TI - Delusional parasitosis associated with phenelzine. AB - A woman developed delusional parasitosis when taking phenelzine. The delusion occurred in an agitated hypomanic state and was preceded by an intense pruritus. It completely remitted following withdrawal of phenelzine combined with a low dose of haloperidol (1 mg/day) for several days. This unusual psychopathology is probably encountered more by dermatologists than by mental health professionals. PMID- 1756353 TI - The co-existence of erotomania and Capgras' syndrome. AB - A case of secondary erotomania co-existent with Capgras' syndrome presented with features that have not been reported before. The case is suggested to be a variant of de Clerambault's syndrome. The role of cultural factors in altering the clinical picture is insignificant. PMID- 1756354 TI - Isolated cataplexy of more than 40 years' duration. AB - For over 40 years, a 55-year-old woman had suffered from cataplexy, which had been mistakenly identified as hysteria. Sleepiness, hypnagogic hallucinations and sleep-onset paralysis were not present. This is the longest duration of isolated cataplexy reported so far. PMID- 1756355 TI - Conditional probability and sibling sex. PMID- 1756356 TI - Apparent decrease in schizophrenia. PMID- 1756357 TI - The human brain and political behaviour. PMID- 1756358 TI - 'Compulsive' water drinking in psychosis... PMID- 1756359 TI - . . . and mentally handicapped people. PMID- 1756360 TI - Negative symptoms of schizophrenia. PMID- 1756362 TI - Neuroleptic malignant syndrome. PMID- 1756361 TI - Hospital anxiety and depression scale. PMID- 1756363 TI - Psychiatrists and citizens. PMID- 1756364 TI - Promoting the correct use of psychotropic drugs. PMID- 1756365 TI - Affect logic. PMID- 1756366 TI - Admission rates, detention rates and socioeconomic deprivation. PMID- 1756367 TI - Depression and polycythaemia. PMID- 1756368 TI - What's in a name? PMID- 1756369 TI - Monozygotic male triplets discordant for psychosis. PMID- 1756370 TI - Chloroquine-induced psychiatric complications. PMID- 1756371 TI - Aggression and multiple sclerosis. PMID- 1756372 TI - Sudden cardiac death and antidepressants. PMID- 1756373 TI - Hair loss associated with fluoxetine. PMID- 1756374 TI - Cortical cells' physiology following visual split brain in developing cats. AB - We have studied physiologically whether visual cortex cells in areas 17 and 18 of split-brain cats preserve their performance despite the blockage of both binocularity and of interhemispheric communication. The absolute majority of the cells in cats underwent split-brain surgery as kittens and adults and were driven by the ipsilateral eye, resulting in the absence of interhemispheric interaction. Similar results were found in cats and kittens that underwent only chiasm split surgery, although some recovery of callosal transfer was found in the latter. A remarkable loss of binocularity was found when only callosal transection was performed, both in adult cats and in kittens, although some ipsilateral eye dominance was observed in the latter. As to the deprived cats, while in the inexperienced hemisphere (ipsilateral to the deprived eye), the majority of the cells was visually unresponsive, in the contralateral (experienced) hemisphere, the majority was responsive. A considerable reduction in responsiveness was found in the callosally transected cats and kittens. Generally, a degradation of function was found in the various properties as a result of chiasmal and/or callosal transection. The main effect is the increased number of cells with diffuse and incomplete receptive fields. There was also a reduction in the proportion of orientation-selective cells, mainly in the split-brain cats. It was concluded that, despite the high amount of hemispheric independency in the normal brain, the integrity and simultaneous action of the two hemispheres are needed for the normal functioning of visual cortex cells. PMID- 1756375 TI - Time course of rat sleep variables assessed by a microcomputer-generated data base. AB - A microcomputer-based system is described that detects, counts and stores cortical delta and sigma waves, hippocampal theta waves and electromyographic activities in the rat by building matrices with the incidence of those four variables (columns) in 15-second bins (rows). Data tables are submitted to statistical, graphics and spread-sheet software to assess internal organization of sleep episodes and 24-hour distribution of sleep variables. Within sleep episodes, cross-correlograms reveal a delta-sigma-theta sequence, while autocorrelograms quantify clustering and periodicity of variables. Sleep accumulates in the lights-on phase, with high concentration of delta at the beginning of this sleep-predominant phase and of sigma and theta in its second half. These are notable similarities with human sleep architecture. Simple procedures for data reduction into standard behavioral state diagnosis are demonstrated. The low cost of personal computers and data acquisition interfaces facilitates the automation of complex paradigms by ad hoc on-line programs that produce as output a data base that can be processed by standard software, providing a fluid pathway of automated acquisition, analysis and presentation of data. PMID- 1756376 TI - Tetrahydroaminoacridine improves passive avoidance retention defects induced by aging and medial septal lesion but not by fimbria-fornix lesion. AB - The present study examines whether tetrahydroaminoacridine (THA) can improve the deterioration in passive avoidance (PA) retention performance induced by medial septal (MS) and fimbria-fornix (FF) lesions in young rats or by aging. Retention of young MS-lesioned rats was improved by pretraining injection of THA at 3 mg/kg, but not by THA at 1 mg/kg or by either of the posttraining doses of THA (1 and 3 mg/kg). Pretraining injections of THA at 1 or 3 mg/kg had no effect on the PA retention performance of FF-lesioned rats. Age-induced PA failure was alleviated by pretraining administration of THA at 1 and 3 mg/kg. Posttraining injections of THA (1 or 3 mg/kg) had no effect on PA retention performance of aged rats. These results demonstrate that 1) THA may improve hippocampal cholinergic denervation-induced functional deficits and 2) some of the age related PA deficits may be due to a cholinergic deficit and can be reversed with THA. PMID- 1756377 TI - Melatonin modifies the spontaneous multiunit activity recorded in several brain nuclei of freely behaving rats. AB - Melatonin, a pineal hormone, released photoperiodically, was administered systemically in rats, previously implanted with semimicroelectrodes into six different brain structures. The multiunit electrical activity of these structures was recorded for 10 min before and 60 min after melatonin administration in unanesthetized, freely moving rats. Different melatonin doses (100, 200, 500, and 1000 micrograms/kg) produced changes in the electrical activity of all tested structures. However, amygdala, rostral hypothalamus and mesencephalic reticular formation showed the most important changes. The main effect induced by melatonin was a dose-related decrease of the spontaneous electrical activity. The significance of these effects is discussed within the context of the behavioral and endocrinological effects of melatonin. PMID- 1756378 TI - Desmethylimipramine promotes recovery of self-stimulation from the prefrontal cortex following footshock. AB - Intracranial self-stimulation (ICSS) was assessed from the prefrontal cortex in CD-1 mice immediately (0 h), 24 h and 168 h following exposure to uncontrollable footshock. Marked reductions in ICSS rates were observed in all mice immediately following the stressor. Although the ICSS alterations were transient in some animals, ICSS rates were reduced in the majority of animals 24-h and 168-h poststressor. Mice of either the shock or no shock treatment groups were administered either saline or desmethylimipramine (DMI, 5 mg/kg x 2) for 20 consecutive days. Chronic DMI ameliorated the stressor-induced ICSS deficits from the prefrontal cortex. Potential explanations for the stressor-provoked variations in ICSS and the effects of DMI are discussed. PMID- 1756379 TI - Depletion of calcitonin gene-related peptide in perivascular nerves during acute phase of posthemorrhagic vasospasm in the rabbit. AB - The behaviour of various neuropeptides during early and late vasospasm following experimental subarachnoid hemorrhage has been investigated by several authors. Recently, a reduction of the content of vasodilatory neuropeptides (vasodilatory intestinal peptide, substance P and calcitonin gene-related peptide) has been demonstrated in the perivascular nerves of cerebral arteries after few days from induction of experimental subarachnoid hemorrhage. In the present immunohistochemical study, the authors investigated secretion and expression of CGRP a few minutes after injection of autologous blood into the cisterna magna of the rabbit. The authors propose that the marked decrease of calcitonin gene related peptide immunoreactivity in the perivascular nerves, observed after experimental subarachnoid hemorrhage, is due to compensatory secretion of the peptide. PMID- 1756380 TI - Calcitonin gene-related peptide-like immunoreactivity and its relation with neurotensin- and corticotropin-releasing hormone-like immunoreactive neurons in the bed nuclei of the stria terminalis in the rat. AB - The distribution of calcitonin gene-related peptide (CGRP)-like immunoreactive (LI) nerve cells and terminals (BST) was studied in the rat. Only the fusiform nucleus was found to consistently contain CGRP-LI neurons. The CRGP-LI terminals had a wide distribution in the BST, being most numerous in the oval and the fusiform nuclei. In the oval nucleus the CGRP-LI terminals formed characteristic "baskets." Since the oval nucleus was known to be studded with neurotensin (NT)- and corticotropin-releasing hormone (CRH)-LI neurons, the relationship of the CGRP-LI nerves to NT- and CRH-LI neurons was investigated by means of a double immunostaining technique. A part of the CGRP-LI baskets were found to contain NT- or CGRP-LI neurons. The possible involvement of the CGRP/NT or CRH relationship in reciprocal connection between the BST and the parabrachial nucleus and in cardiovascular regulation is discussed. PMID- 1756381 TI - Muscarinic cholinoceptive neurons in the frontal cortex in Alzheimer's disease. AB - The cellular distribution of muscarinic acetylcholine receptor protein in the frontal cortex of Alzheimer (AD) patients, age-matched and middle-aged controls was assessed quantitatively by means of immunohistochemistry using the monoclonal antibody M35. As shown previously in biopsy cortices, mainly layer II/III and V pyramidal neurons were immunolabeled. Neither distribution nor numbers of labeled cells displayed significant differences between the groups investigated. This is in accordance with the results of ligand binding studies that mostly failed to reveal different binding characteristics in AD compared to controls. Muscarinic and nicotinic receptor proteins have been shown to be colocalized in many cholinoceptive pyramidal neurons. Since nicotinic receptors--in contrast to muscarinic receptor proteins--are severely reduced in AD, this indicates a selective impairment of nicotinic receptor expression and not a significant death of cholinoceptive neurons per se. PMID- 1756382 TI - Hippocampal and cortical EEG activity in rats with transected hypothalamus. AB - The brain was transected in eight rats: the transection passed through the posterior pole of the superior colliculi and ended down at midhypothalamic level. The EEG activity in the dorsal hippocampus and cortex showed continuously slow, high amplitude waves. Thus the posterior hypothalamus is critical for the previously described hippocampal theta rhythm found in rats transected at the posthypothalamic level. PMID- 1756383 TI - Development of transient acetylcholinesterase staining in cells and permanent staining in fibers in cortex of rat brain. AB - The development of the acetylcholinesterase (AChE) texture of the cortex of the rat brain was studied during the first three weeks of life. The Tago technique enables visualization of both AChE+ cells and fibers with both shown in exquisite detail making quantification possible. At each age--0 (birth), 7, 14, 21 and 60 days (adult)--four brain areas were studied (cingulate, dorsal neocortex, lateral neocortex and olfactory) at each of three coronal planes in the brain (anterior, intermediate, posterior). Fiber density reached adult levels by Day 21 in cingulate cortex in intermediate and posterior planes. In other areas fiber density reached adult levels by Day 14 indicating a high rate of fiber growth during the first two weeks of life since at birth rat cortex is innervated only by a sparse AChE+ fiber invasion into neocortex in the anterior plane. Fiber density did not regress after adult levels were reached, however, cell staining showed a different pattern. At birth many lightly stained cells were seen in the olfactory cortex in all three planes, but other areas were devoid of cells. In all areas there was a peak at Day 7 in number of cells stained and in intensity of cells staining with a gradual decline in cell staining until by Day 21 very few stained cells were seen in the cortex (typical adult pattern). PMID- 1756384 TI - The role of platelets in the development of cerebral vasospasm. AB - A possible role of platelet-derived 5-HT was examined concerning the pathogenesis of cerebral vasospasm. Intracisternal injection of 5 ml of platelet-rich plasma (PRP; approximately 7.5 x 10(8) platelets) induced not only acute (1 h) but also chronic (7 days) angiographically evident cerebral vasospasm in dogs. Sympathetic perivascular nerves on cerebral arteries showed no remarkable change following repeated injections of PRP, as the dense distribution of catecholamine fluorescence and neuropeptide Y-like immunoreactive nerve fibers on Day 7 was comparable to findings in the preinjection controls. While there were no 5-HT immunoreactive fibers in the cerebral arteries of control animals, numerous 5-HT immunoreactive fibers were present in the PRP-injected animals. These results suggest that 5-HT, presumably released from extravasated platelets, may be taken up by nerve endings and act as a vasoconstrictor transmitter in the pathogenesis of chronic vasospasm. PMID- 1756385 TI - A monoclonal antibody that labels Purkinje cells in the rat cerebellum. AB - A monoclonal antibody (MAb-1D10), generated by immunizing Balb/c mice with homogenized bovine retinal tissue, labeled the Muller cells in the bovine retina and the Purkinje cells of the rat cerebellum. In the neonatal rat cerebellum, immunoreactivity for MAb-1D10 appeared first in the ventral regions of vermis (lobuli I-III and IX-X) on the 11th postnatal day (P11), while in the dorsal vermis and cerebellar hemisphere, the immunoreactive Purkinje cells were detected on P13. Western blotting analysis disclosed that MAb-1D10 recognized bovine retinal polypeptides with mol.wt. of 48 kDa. Transplantation of the rat cerebellar primordia on 16th embryonic day demonstrated large and round cells with a linear arrangement in the grafts surviving well in the host rat striatum after 50 days of the grafting. These large cells were immunohistochemically labeled by MAb-1D10. No other cells in both the graft and the host striatum were immunoreactive to the MAb. PMID- 1756386 TI - Age- and sex-related differences in the nerve growth factor distribution in the rat brain. AB - Levels of the nerve growth factor (NGF) have been measured in various brain regions of young and aged male and female rats of Wistar strain by means of a highly sensitive two-site enzyme immunoassay system for beta-NGF. Among the ten regions examined, the amount of NGF per wet weight of tissue was found to be highest in the hippocampus, irrespective of the sex and age. The NGF concentration in the hippocampus of female rats at 3 months of age was comparable to that of same aged males. Further, there was no significant difference in the NGF levels of the hippocampus between young and age males. However, the NGF level was significantly lower in aged females as compared to that in 3- or 4-month-old females, and hence the marked male-female difference was found in the NGF levels in aged Wistar rats. PMID- 1756387 TI - Adinazolam affects biogenic amine release in hippocampal CA1 neuronal circuitry. AB - The new triazolobenzodiazepine, adinazolam, which has dual anxiolytic and antidepressant activities, was studied for its effects on hippocampal CA1 norepinephrine and serotonin release in chloral hydrate-anesthetized rats, with in vivo voltammetry. Norepinephrine signals were further characterized in vivo by the detection of a significantly increased norepinephrine signal (mean = 25.8%) (p less than 0.003) after intraperitoneal administration of the alpha 2 adrenoreceptor antagonist, yohimbine, and by the detection of a significantly decreased norepinephrine signal (mean = 20.1%) (p less than 0.037) after intraperitoneal administration of the alpha 2 adrenoreceptor agonist, clonidine. Time course studies showed that the anxiolytic-antidepressant drug adinazolam (10 mg/kg IP) significantly decreased hippocampal norepinephrine release (mean = 26.2%) (p less than 0.007). The norepinephrine signal was further significantly decreased by adinazolam (mean = 16.4%) (p less than 0.009) after an additional 2 mg/kg IP injection. Serotonin release, which was detected with norepinephrine in sequence, was also significantly decreased by adinazolam (10 mg/kg IP) (mean = 22.4%) (p less than 0.002). The supplemental dose of adinazolam (2 mg/kg IP), however, did not significantly alter serotonin release any further (p less than 0.307). The findings show that the mechanism of action of adinazolam occurs simultaneously on presynaptic release mechanisms for norepinephrine and for serotonin in CA1 region of hippocampus. These findings implicate that noradrenergic and serotonergic release mechanisms may be responsible in part for the dual anxiolytic-antidepressant efficacy of adinazolam. PMID- 1756388 TI - Parvalbumin-positive neurons in rat dorsal hippocampus contain muscarinic acetylcholine receptors. AB - The present study describes the colocalization of muscarinic acetylcholine receptors (mAChRs) and the calcium-binding protein parvalbumin (PARV) in nonpyramidal neurons of the rat dorsal hippocampus by means of dual-label immunocytochemistry. Fifty-two percent of all muscarinic cholinoceptive nonpyramidal neurons contain parvalbumin. Conversely, the vast majority (88.4%) of all PARVergic neurons possess mAChRs. The PARVergic neurons embedded within the CA1 pyramidal cell layer are nearly all (98.9%) immunopositive for mAChRs. These results indicate that the cholinergic septohippocampal projection represents a major afferent system upon the inhibitory PARVergic neurons. PMID- 1756389 TI - Fever induced by macrophage inflammatory protein-1 (MIP-1) in rats: hypothalamic sites of action. AB - The purpose of this study was to clarify the central site of action as well as functional characteristics of the febrile response of the cytokine, macrophage inflammatory protein-1 (MIP-1). Guide cannulae for microinjection were implanted stereotaxically in the rat just above the pyrogen and thermosensitive area of the anterior hypothalamic, preoptic area (AH/POA). Following postoperative recovery, the body temperature of each rat (Tbo) was monitored during an experiment by a colonic thermistor probe at 0.5-1.0-h intervals. When MIP-1 was microinjected in a 0.5-microliter volume into the AH/POA in one of eight concentrations ranging from 0.0028 nanograms (ng) to 9.0 ng, an intense monophasic or biphasic fever was evoked. The MIP-1-induced increase in the Tbo of the rat was characterized by its short latency of 15 to 30 min and an inverse dose-response curve. Measures of mean latency and maximal rise in Tbo following MIP-1 confirmed the potency of this dose. Although the dose of 0.028 ng produced a fever of over 2.0 degrees C with a latency of only 15 min or less, the hyperthermic response became less intense as the dose of MIP-1 was increased. An anatomical mapping of sites of microinjection which reacted to MIP-1 in mediating fever revealed that the medial portion of the POA of the rat just rostral to the border of the AH was the region of maximum sensitivity to the cytokine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756390 TI - Intrastriatal implants of fetal mesencephalic cells attenuate the increases in striatal proenkephalin mRNA observed after unilateral 6-hydroxydopamine-induced lesions of the striatum. AB - Unilateral injections of 6-hydroxydopamine (6-OHDA) cause significant bilateral increases in striatal proenkephalin (PEK) mRNA in rat brain. We have tested the possibility that implantation of fetal mesencephalic cells can normalize these changes. Two types of grafts were used: 1) embryonic day-15 mesencephalic cells and 2) embryonic day-15 cells which have been modified with a retroviral vector containing a cDNA for protein kinase C (PKC). At two months after grafting, both cell types cause significant attenuation of the increases which occurred on the side of the lesion. However, only the PKC-modified cells cause normalization of the changes on the contralateral side. These observations indicate that, in addition to normalizing supersensitive striatal dopamine (DA) D2 receptors, embryonic cells can also attenuate the alterations in PEK mRNA observed after lesions of the nigrostriatal DA system. The finding that the PKC-modified cells caused bilateral effects in the striatum suggests that second messenger systems may play a role in the bilateral improvement reported in parkinsonian patients who had gotten unilateral intrastriatal transplants. PMID- 1756391 TI - Effects of in ovo estradiol benzoate treatments on sexual behavior and size of neurons in the sexually dimorphic medial preoptic nucleus of Japanese quail. AB - In male Japanese quail, the injection of estradiol benzoate (EB) in the egg causes a complete loss of the testosterone (T)-induced copulatory behavior (behavioral demasculinization). This treatment is only effective if performed before day 12 of incubation. This suggests that embryonic estrogens affect in a permanent way brain structures controlling sexual behavior. The medial preoptic nucleus (POM) is the only sexually dimorphic brain nucleus identified in quail and it is a key center for the action of T on behavior. Recent morphometric studies revealed that the dorsolateral population of neurons in the POM is sensitive to variations of plasma T levels in adult males but not in females. These effects are not observed in the medial part of the POM. This sexually differentiated feature might therefore be organized by the embryonic hormonal environment. Quail embryos of both sexes were treated with EB or received a control injection either on day 9 or on day 14 of egg incubation and the cell size in the dorsolateral and medial POM was evaluated by classical morphometric techniques. EB treatment on day 9 decreased cell size in the dorsolateral POM neurons of males but had no effect in females. No effect was also observed when the treatment was performed on day 14. The medial POM neurons were not affected. The decrease in neuronal size observed in the dorsolateral POM of males treated with EB on day 9 was correlated with their behavioral demasculinization. Some of these males showed a weak sexual behavior during the tests and in parallel had significantly larger neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756392 TI - Dopaminergic regulation of quiet biting attack behavior in the cat. AB - The present study provides evidence for the involvement of dopamine in the regulation of quiet biting attack behavior. Utilizing monopolar electrodes, quiet biting attack was elicited by electrical stimulation of lateral hypothalamus in five cats. After stable baseline response latency values were established, the nonselective dopamine agonist, apomorphine, was administered peripherally (IP, 1.0, 1.4 and 1.8 mg/kg), and its effects upon the attack response were identified. Apomorphine significantly facilitated the occurrence of quiet biting attack in a dose- and time-dependent manner. Conversely, quiet biting attack behavior was also suppressed in a dose- and time-dependent manner by the selective D2 antagonist, spiperone (0.2, 0.4 and 0.8 mg/kg), but not by the selective D1 antagonist, SCH 23390 (0.8 mg/kg). Moreover, pretreatment with spiperone (0.2 mg/kg) completely blocked the facilitatory effects of 1.4 mg/kg of apomorphine, while SCH 23390 (0.8 mg/kg) pretreatment failed to alter apomorphine induced facilitation of the attack response. In addition, neither apomorphine nor spiperone altered response latencies for hypothalamically elicited circling behavior. The results suggest that dopamine plays a significant role in the regulation of quiet biting attack behavior. PMID- 1756393 TI - Dexamethasone inhibits food intake suppression induced by low doses of interleukin-1 beta administered intracerebroventricularly. AB - Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1 beta (rhIL-1 beta, 0.125 to 2.0 ng/rat) dose-dependently suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. ICV infusion of bovine serum albumin (BSA), or heat-treated rhIL-1 beta had no effect on food intake. Pretreatment with dexamethasone (200 micrograms/rat, intraperitoneal) blocked the food intake suppression induced by low doses of rhIL-1 beta. This ability of dexamethasone, a synthetic corticosteroid, may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression. PMID- 1756394 TI - Sensory response enhancement and suppression of monkey primary somatosensory cortical neurons. AB - Vibratory stimulus-related responses were recorded from monkey primary somatosensory cortical (SI) neurons while animals performed two tasks. In the movement task, vibratory stimuli served as the go-cue for wrist flexion or extension. In the no-movement task, movements normally made in response to vibratory stimuli were extinguished. Area 3a, 3b, and 1 neurons with deep receptive fields (RFs) exhibited greater stimulus-related activity during the movement task than during the no-movement task. Area 3b neurons with cutaneous RFs were similarly enhanced during the movement task, whereas area 1 neurons with cutaneous RFs were less responsive to vibratory stimuli during the movement task. These results suggest that motor-set and/or selective attention may modulate the responsiveness of SI neurons to peripheral stimuli and that changes in sensory responsiveness in SI neurons differ as a function of their cortical location and RF type. PMID- 1756395 TI - [Occupational asthma: current and future perspectives. The point of view of an expert]. AB - Occupational asthma remains a difficult problem for physicians and for experts. The prevalence of occupational asthma is underestimated and depends on industrial agent and conditions of work. Diagnosis is made based on detailed description of the patient's work environment, on skin and serological tests, and on lung function tests including non-specific bronchial provocation tests. Rhinomanometry, and peak flow rate measurements may also be useful. Bronchial provocation tests should be performed by experienced staff in a hospital setting with facilities for resuscitation. The prognosis of occupational asthma is variable: --some patients with short and limited exposure may fully recover if their disease is early recognized and appropriate measures are taken; --however, many patients do not recover completely after removal of the responsible agents. Clinical symptoms and bronchial hyperreactivity persist and respiratory insufficiency may develop. The patterns of occupational asthma are changing rapidly, in parallel with industrial evolution: nowadays, bakers's asthma is less frequent than it used to be. Asthma triggered by wood dust and in particular western red cedar (which is exported all over the world) is increasingly recognized. Isocyanates and, in particular toluene isocyanate, are widely used in plastics and paints. Preventive measures have succeeded in decreasing the incidence of asthma caused by exposure to isocyanates. Computer industry has recently developed in many countries. It requires the use of numerous hazardous and highly toxic materials that are potentially responsible for occupational asthma; attention should be given to respiratory diseases especially in industrializing countries (such as Eastern Asian countries). Preventive measures include safety rules, replacement of harmful materials by less toxic agents and detection of susceptible workers. Regulation must be defined under experts' control to continuously match the rapid changes in modern industry. PMID- 1756396 TI - [The lipid profile of the French male 20-year-old population]. PMID- 1756397 TI - [Eulogy on Stephane Thieffry (1910-1990)]. PMID- 1756398 TI - [Violence within the family on a continental scale. Reflections on an ongoing European study]. PMID- 1756399 TI - [The usefulness of vaccination in elderly persons]. AB - The antitetanus, antipneumococcal and antiinfluenza immune status, as well as the efficacy of vaccination have been evaluated in the elderly. Ages of the studied populations ranged from 60 to 98 years. Before vaccination, only half of the tested population was found to be protected against tetanus. Immunization resulted in 80% coverage of this population. Prior to antipneumococcal vaccination, 32% of the tested sera did not contain a "potentially" protective antibody titre. Vaccination resulted in 100% seroconversion. It was verified that 100% of tested sera contained antibodies (greater than 10 U.H.A./ml) directed to the former Singapore antigen and 99.2% and 66.7%, respectively, to the newly immerged Shanghai and Yamagata antigens (present in the administered vaccine). Following vaccination, 100% of the sera exhibited antibody titres higher than 10 U.H.A./ml to the Singapore and Shanghai antigens, and 90.5% to the Yamagata antigen. It can be concluded from the reported results that antitetanus, antipneumococcal and antiinfluenza vaccinations should be systematically given to all individuals beyond 60 years of age, since these vaccinations are innocuous and confer extended vaccinal coverage. PMID- 1756400 TI - Intolerable, excruciating, and troublesome: military ambulance technology, 1793 1880. PMID- 1756401 TI - Sterilizing surgical instruments: a curator's historical perspective. PMID- 1756402 TI - Decontamination and sterilization of medical instruments in museums. PMID- 1756403 TI - Radioactive and radium sources in medical museums. PMID- 1756404 TI - The preservation and disposition of hazardous substances and controlled drugs in museum collections. PMID- 1756405 TI - Arsenic, old lace, and stuffed owls may be dangerous to your health: environmental concerns for museum personnel. PMID- 1756406 TI - [Evaluation of myocardial perfusion by planar scintigraphy at rest and in exertion using T1 201 and Tc 99m SestaMIBI, respectively]. PMID- 1756407 TI - [Demonstration of the excitatory effect of the thalamo-subthalamic efferent from the parafascicular nucleus]. AB - The synaptic effect of the projection from an intralaminar thalamic structure, the parafascicular nucleus, to the subthalamic nucleus was investigated through extracellular recordings of subthalamic unit activities. Electrical stimulation of the parafascicular nucleus caused a complex response with two successive excitatory phases. The first excitation was assumed to be monosynaptically driven since it was not affected by pallidal lesion or transsection of the internal capsule. Pharmacological activation of the parafascicular neurons through microinjections of carbachol elicited a prolonged increase in the subthalamic discharge rate. These results suggest that the intralaminar parafascicular nucleus contributes to the activation of subthalamic neurons. PMID- 1756408 TI - Expression of a gene encoding a novel potential IGF binding protein in human tissues. AB - We have shown in a previous study that the expression of an as yet unidentified, embryonic gene (nov) encoding a potential IGF binding protein was upregulated in all of eight virally-induced avian nephroblastomas tested. We now report that homologous sequences are conserved in human DNA and are expressed in normal human bone marrow, thymic cells and in one nephroblastoma. PMID- 1756409 TI - [Adaptative differential maturation of neurohypophyseal provasotocin in amphibians: presence of hydrin 2(vasotocinyl-glycine) in anura but not in urodela]. AB - Occurrence of hydrin 2 (vasotocinyl-glycine), an intermediate in the provasotocin processing, has been shown in the neurointermediate lobe of the pituitary of semi aquatic or terrestrial amphibian species belonging to the order Anura, namely Rana esculenta, R. temporaria, R. pipiens (Ranidae), and Bufo bufo, B. marinus, B. ictericus (Bufonidae). In contrast hydrin 2 appears absent in species belonging to the order Urodela, namely the axolotl Ambystoma mexicanum (Ambystomidae) and the pleurodele newt, Pleurodela waltlii (Salamandridae). Whereas water transport through the skin and the urinary bladder is stimulated by vasotocin and hydrin 2 in anuran species, this stimulation is known not to occur in urodele species. PMID- 1756410 TI - [Biosynthesis of ecdysteroids by prothoracic glands in Pieris brassicae (Lepidoptera insect). Conversion in vitro of radiolabelled precursor of 3 dehydroecdysone]. AB - Ecdysteroids secreted by prothoracic glands of Pieris brassicae were measured by enzyme immunoassay, after HPLC separation. Both ecdysone and 3-dehydroecdysone, as a major product, are produced. Two radiolabelled putative precursors were converted by Pieris glands in vitro: [3H] ketodiol was converted into ecdysone at a low rate; [3H]3-oxoketodiol was efficiently converted, mainly into 3 dehydroecdysone. These data make 3-oxoketodiol a good candidate for an intermediate in ecdysteroid biosynthetic pathway. PMID- 1756411 TI - [Obtention with polymerase chain reaction (PCR) of gene rbcL in the scrophulariaceae holoparasite Lathraea clandestina L. Comparison with autotroph Digitalis purpurea L. and Melampyrum pratense L]. AB - Amyloplastid DNA was extracted from the Scrophulariaceae holoparasite Lathraea clandestina L. and then purified. An rbcL gene amplification was performed using polymerase chain reaction. Two regions of well conserved sequences in Tobacco, Spinach and Maize rbcL gene have been used as primers. PCR yields a sequence of about 1,230 base pairs, almost nine tenths of the rbcL coding region. Identical results were obtained with plastid DNAs from Tobacco and two other species of Scrophulariaceae: the non-parasitic Digitalis purpurea L. and the hemiparasite Melampyrum pratense L. PCR products were digested with BamHI restriction enzyme and no changes were shown in the localization of the restriction site whatever the species assayed. Identical restriction patterns were also observed with Tobacco and Digitalis PCR products restricted with PstI and KpnI, whereas Melampyrum and Lathraea exhibited a different restriction pattern with PstI. So, despite slight differences, some analogies between Lathraea and Digitalis or Tobacco gene were evidenced. Cloning and sequencing of these PCR products could give a more accurate response to the following question: to what extent have changes occurred in the rbcL gene in a plant which lacks chlorophyll? PMID- 1756412 TI - [Oral and parenteral immunization with HIV immunosome induce the secretion of IgA specific of HIV-1 in the salivary and the production of circulatory IgA in mice and rabbits]. AB - Given the sexual transmission of HIV, the establishment of a genital mucosal immunity through secretory IgA may be necessary to achieve protection. We have investigated if repeated stimulations of oral mucosa with HIV-Immunosomes would lead to the production of secretory IgA in saliva and also, if such an oral immunization could prime the immune system to an early systemic immune response following a parenteral immunisation with a low dose of the antigen. HIV-1 gp 160 specific secretory IgA were detected in the saliva of all rabbits orally immunized with HIV-Immunosomes. As early as one week after the parenteral immunization, high titers of serum IgA, IgM and IgG were detected both in mice and rabbits that had been orally stimulated with the antigen. These antibodies could neutralize HIV infectivity in vitro. Animals that were immunized only parenterally showed a very weak humoral immune response. PMID- 1756413 TI - A genetic response to high altitude hypoxia: high hemoglobin-oxygen affinity in chicken (Gallus gallus) from the Peruvian Andes. AB - A population of chicken (Gallus gallus) from the Peruvian Andes (4,000 m) carrying a high hemoglobin-oxygen affinity has been identified. This property remained stable after over 1 year residence at sea level and was transmitted to the descendants born at sea level. Chicken were introduced in South America during the Spanish conquest and therefore their adaptation time to high altitude is less than 500 years. This finding shows that a genotypic change in hemoglobin function can occur in an extremely short evolutionary time and leads to some reflections on the high altitude adaptation of the mammals that migrated to South America during the great Plio-Pleistocene interchange. PMID- 1756414 TI - [Fetal thymus and thymuline stimulate the in vitro proliferation of oogonia in the fetal rat ovary]. AB - In rat ovaries explanted on day 13.5 p.c. and cultured in vitro for up to 6 days, the number of germ cells is enhanced in thymulin-supplemented medium and/or after co-culture of the ovarian explants with foetal thymic tissue compared to ovaries cultured in synthetic medium. Corticosterone added to the medium prevents the secretion of thymulin by the foetal thymus and in that condition the thymus does not influence the proliferation of oogonia. These results provide additional evidence that the pituitary-adrenal-thymic axis might be involved in the control of oogonia proliferation in vivo, taking into account our previous experimental finding that the number of germ cells is increased in ovaries of hypophysectomized foetuses. PMID- 1756415 TI - [Long ascending fibers in the dorsal column of a teleost fish: a disynaptic pathway connecting sense organs to cerebellum]. AB - In spite of the generally accepted opinion that long ascending proprioceptive and tactile fibers do not occur in the spinal dorsal columns of teleost fish, it was demonstrated with degeneration and axonal transport tracing methods that such dorsal column fibers exist in the teleost fish Gnathonemus petersii. These fibers are in fact common spinal afferent fibers originating in spinal ganglion cells. They connect the peripheral sense organs with the lateral funicular nuclei (Fl2) in which the dorsal column fibers terminate, directly through the dorsal columns. In contrast to the dorsal column nuclei of higher vertebrates, the Fl2 nuclei do not project to the diencephalic thalamus but to the caudal lobe and the second lobe (C2) of the corpus cerebelli. Thus, sense organs and cerebellum are connected by a disynaptic pathway. Since the caudal lobe projects directly to the electrosensory lobe, that is, to the target of electrosensory afferents, the presence of a disynaptic pathway in G. petersii suggests the existence of a proprioceptive control of the electrosensory input. PMID- 1756416 TI - [Lateralization in cats in a pointing task of the anterior limb towards a moving target]. AB - In a group of 44 cats overtrained on a task where they had to reach for a moving target, paw performance and paw preference were investigated. More than half of the cats (n = 23) were strongly lateralized in that they used one of their paws to perform more than 90% of the reaching attempts. Among these lateralized cats, left-pawed ones (n = 17) significantly exceeded right pawed-animals (n = 6). Investigating both the accuracy and speed scores, the comparison between lateralized and non-lateralized cats (using a criterion of 90% lateralization) showed that although the accuracy scores did not differ, lateralized cats were significantly quicker to trigger their movement. No difference was found concerning the movement time. For the whole group of 44 cats the comparison between the performance levels obtained with their two forepaws showed that the more frequently used paw was significantly more accurate and faster to trigger and to execute the movement than the less used paw. This study shows that, in pointing towards a moving target, cats display an asymmetry in paw preference that is associated with a performance asymmetry. PMID- 1756417 TI - Physician management of hyperlipidemia in Saskatchewan: temporal trends and the effect of a CME program. AB - OBJECTIVE: To assess current trends in the management of hyperlipidemia by Saskatchewan physicians, and to evaluate the effect of a specific continuing medical education (CME) program. DESIGN: Using a quasi-experimental design, physicians in an intervention area received the CME program while those in a comparison area did not. Management of hyperlipidemia was assessed before and after the program via a self-administered questionnaire. SETTING: All family physicians, general internists and cardiologists practising in the two areas were eligible. SUBJECTS: Of 439 eligible physicians, 308 (70%) completed the first survey, while 268 of 447 (60%) completed the second survey. Analysis was conducted on the 221 physicians who completed both surveys. INTERVENTION: Physicians in the intervention area received printed materials and attended a series of seminars between November 1988 and February 1989. Program content was based upon the recommendations of the Canadian Consensus Conference on Cholesterol (1988). MAIN RESULTS: Over the study period the mean level of serum cholesterol considered 'ideal' for a 40- to 60-year-old male decreased significantly from 5.43 to 5.03 mmol/L (P less than 0.001). The mean level at which diet therapy was begun decreased from 6.60 to 5.78 mmol/L (P less than 0.001) with a significantly greater proportion of physicians in the intervention area (58.0%) than in the comparison area (43.2%) initiating therapy in the 5.2 to 5.6 mmol/L range (P = 0.03). The mean level of serum cholesterol at which drug therapy is begun also decreased from 7.59 to 6.82 mmol/L (P less than 0.001), with a significantly greater proportion of physicians in the intervention (41.6%) than in the comparison area (25.0%) starting therapy in the 6.2 to 6.6 mmol/L range (P = 0.03). CONCLUSIONS: The management of hyperlipidemia reported by physicians in Saskatchewan changed dramatically between July 1988 and March 1989. The effect of the CME program is modest in comparison with this large temporal trend. The study provides further evidence that significant changes in the practice patterns of groups of physicians will only occur when the educational process is highly focused and personalized. PMID- 1756418 TI - Survey of cardiac pacing in Canada. AB - The status of cardiac pacing in Canada in 1989 was determined from data provided by 62 of 128 physicians surveyed (48% response) and four major manufacturer/distributors. A questionnaire designed for the IXth World Symposium on Cardiac Pacing was used. DEMOGRAPHICS: There were five implant hospitals per million population, 65% community based and 35% university affiliated; 63% of implanters were surgeons. There were 279 new implants and 46 replacement procedures per million population. INDICATIONS: Sinus node disorders accounted for 44.6% of implants, atrioventricular block 43.2% (fixed 24.4%, intermittent 12.0%, incomplete 6.8%), tachycardias 2.9%, drug-induced bradycardia 3.1%, and other (including automatic implantable cardioverter defibrillators) 6.2%. TECHNOLOGY: Single chamber units were implanted in 78.6% of patients, and dual chamber in 22.7%, and 19.5% of the total were rate-adaptive. Unipolar leads were used in 57.1% of atrial and 53.2% of ventricular insertions; 40.4% of atrial and 5.8% of ventricular leads were active fixation. The pervenous sheath introducer technique was used in 64.9% of lead insertions. PERIOPERATIVE: Major complications occurred in 2.6% of single and 6.8% of dual chamber primary implants, but mortality was less than 0.1%; 8.4% of replacements were unanticipated; there was no known death from malfunction. Mean hospital stay was 2.7 days for primary implants and 1.4 days for replacement/revisions. CONCLUSIONS: Comparison with prior surveys (1979, 1981, 1985) reveals: increased physician response to the survey questionnaire; relatively stable electrocardiographic indications for implant; a modest increase of new implants per million; continued decrease in replacements; an increase in dual chamber and rate-adaptive pacing; and increased use of active fixation and bipolar electrodes in both atrium and ventricle. PMID- 1756419 TI - Preliminary experience at a Canadian centre with directional coronary atherectomy for complex lesions. AB - OBJECTIVE: To evaluate preliminary experience of directional coronary atherectomy for complex coronary artery lesions. DESIGN: Nonrandomized, sequential patients with coronary arterial lesions that were ostial, eccentric, bulky, recurrent or membranous. SETTING: Cardiac catheterization laboratory of a tertiary referral general hospital. PATIENTS: Twenty-three patients with angina pectoris refractory to medical therapy who were suitable candidates for coronary bypass surgery. INTERVENTIONS: Directional coronary atherectomy with associated balloon angioplasty, if required, to reduce lesion stenosis to less than 25%. MAIN RESULTS: Primary success was achieved in 29 of 33 lesions (88%) by atherectomy alone and in 31 of 33 lesions (94%) by additional use of balloon angioplasty. Atherectomy retrieved tissue in 30 of 33 attempts (91%). One patient suffered Q wave myocardial infarction; one had acute occlusion after atherectomy requiring emergency balloon angioplasty; and one required repair of a false aneurysm of the femoral artery. CONCLUSIONS: Directional coronary atherectomy is safe and efficacious for ostial, bulky and eccentric lesions not optimally suited to balloon angioplasty. Lesions which have tortuous segments immediately beyond, restricting movement of the stiff nose-cone, and which are membranous or bandlike, may not be indicated for directional coronary atherectomy. PMID- 1756420 TI - Long term efficacy of propafenone for prevention of atrial fibrillation. AB - OBJECTIVE: Propafenone, a class IC antiarrhythmic drug, has been successful in the treatment of ventricular and supraventricular arrhythmias. This study retrospectively evaluated the efficacy of propafenone in the prevention of recurrent atrial fibrillation. DESIGN: Propafenone was given to 81 patients (49 males and 32 females, mean age 61 +/- 16 years) with recurrent atrial fibrillation. The mean dose of propafenone was 701 +/- 235 mg. Patients were monitored for recurrent arrhythmias. MAIN RESULTS: Long term follow-up over 30 +/ 1.7 months showed 31 patients (38%) remained on propafenone with complete or partial control of atrial fibrillation. The drug was stopped in 35 due to inefficacy, in 12 due to adverse effects, and in three due to desire for ablation therapy. CONCLUSION: Propafenone may be effective in some patients for long term prevention of atrial fibrillation, although efficacy may decrease over time. PMID- 1756421 TI - Perfusate calcium: effect on cardiac stability and response to ischemia and reperfusion. AB - OBJECTIVE: The aim of this study was to characterize the relationship of perfusate calcium concentration, contractile state and stability of the isolated crystalloid perfused working rat heart preparation, to ischemic duration and functional recovery, at a physiological perfusate calcium concentration. METHODS AND RESULTS: In the first protocol, hearts (n = 6 per group) were aerobically perfused for up to 300 mins with Krebs Henseleit solution containing calcium concentrations (total) of 1.0, 1.2, 1.4, 1.6, 1.8 and 2.5 mmol/L (equivalent to ionized concentrations of 0.76, 0.94, 1.15, 1.21, 1.58 and 2.25 mmol/L, respectively). After 120 mins, aortic flow decreased by less than 20% in all preparations except those perfused with 1.0 mmol/L, which fell by over 60%. For subsequent studies, a calcium concentration of 1.4 mmol/L (ionized calcium 1.15 mmol/L, a value equivalent to plasma ionized calcium) was identified as ideal and shown to be associated with stable function and adequate inotropic reserve. The second protocol was as follows: In additional studies (n = 6 per group), the relationship between normothermic global ischemic duration (with or without cardioplegic arrest) and post ischemic functional recovery was characterized. Increasing the ischemic duration (10, 15, 20, 25, 30, 35 or 40 mins) progressively impaired recovery of aortic flow to 86.7 +/- 3.2%, 71.7 +/- 4.9%, 27.7 +/- 5.0%, 14.5 +/- 12.3%, 0%, 0% and 0%, respectively, in the noncardioplegia group, and to 84.7 +/- 1.7%, 85.0 +/- 2.9%, 78.0 +/- 2.4%, 56.0 +/- 7.8%, 32.2 +/- 6.0%, 6.5 +/- 3.7% and 0%, respectively, in the cardioplegia group. These results were similar to those of previous studies in which 2.5 mmol/L calcium was used in the perfusate. CONCLUSIONS: Perfusion of isolated hearts with perfusate calcium concentrations up to 2.5 mmol/L (total) had no apparent detrimental effect on the stability of the preparation; however, a calcium concentration of 1.0 mmol/L resulted in a rapidly deteriorating preparation. In addition, under the conditions prevailing in the present study, a perfusate calcium content within the physiological range (1.4 mmol/L) appeared not to alter the vulnerability of the rat heart to injury during ischemia and reperfusion. PMID- 1756422 TI - Vasodilator therapy: interaction of nitrates with angiotensin-converting enzyme inhibitors. AB - Nitrates and other nitrosovasodilators are locally acting agents. Their efficacy is reported to depend upon the availability of sulfhydryl groups in vascular smooth muscle. Long term nitrosovasodilator therapy has limited effectiveness, and development of nitrate tolerance has been recognized to be due to exhaustion of the tissue sulfhydryl pool, in addition to vasodilation-induced reflex activation of the neurohumoral system. Under both experimental and clinical conditions it has been demonstrated that N-acetylcysteine and other exogenously introduced sulfhydryl donors potentiate hemodynamic responses to nitrates and reverse nitrate tolerance. The newer group of angiotensin-converting enzyme (ACE) inhibitor drugs has been reported to be effective in reducing afterload and preload in a variety of experimental and clinical trials. Captopril, the first developed ACE inhibitor, and its analogs contain sulfhydryl groups. Although the sulfhydryl group of captopril is not thought to be responsible for its vasodilator action, it can act as a sulfhydryl donor to promote nitrate effectiveness and prevent development of tolerance. Limited experimental and clinical trials on combined therapy with nitrates and captopril have produced promising results. An ingenious prototype compound, S-nitrosocaptopril, has recently been synthesized. This is an exciting new development in vasodilator therapy, but clinical application must await full experimental characterization of this and other identical compounds. PMID- 1756423 TI - Lung liquid production by in vitro lungs from fetal guinea pigs: studies with metabolic inhibitors. AB - Lungs from fetal guinea pigs (62 +/- 2 days of gestation) were supported in vitro for 3 h, and lung liquid production was measured by dye dilution. Eighteen untreated preparations produced fluid at 1.76 +/- 0.30 mL.kg-1 body weight.h-1 during the first hour, with no significant changes in later hours. When inhibitors of respiratory processes were placed in the outer saline during the middle hour, production changed significantly, as follows: (a) sodium iodoacetate at 10(-3) M stopped production (87.2 +/- 10.3 and 100% reductions, successive hours; n = 6), at 10(-4) M it reduced production (60.0 +/- 10.3 and 63.4 +/- 9.3% reduction, successive hours; n = 12); (b) sodium fluoride, 10(-3) M, almost stopped production (93.2 +/- 12.1 and 89.5 +/- 9.3% reductions, successive hours; n = 6); (c) sodium cyanide at high concentration (10(-3) M) reduced production slowly (35.5 +/- 12.3 and 73.1 +/- 22.4%; successive hours; n = 6); (d) sodium azide, 10(-3) M, also reduced production (67.6 +/- 14.2 and 59.7 +/- 14.0%, successive hours; n = 6); total lactate lost rose 1.8 +/- 0.5 fold; (e) dinitrophenol produced strong reabsorptions; at 10(-3) M, production fell 115.4 +/- 15.9 and 113.1 +/- 47.3%, successive hours (n = 4), and at 2 x 10(-4) M it fell 143.8 +/- 33.8 and 153.4 +/- 26.7%, successive hours (n = 6); total lactate lost rose 2- to 3-fold. Control preparations showed no significant changes. The results suggest that lung liquid production requires glycolysis and aerobic metabolism. However, reabsorption appears to continue on glycolysis alone, a particularly useful situation for neonates suffering respiratory distress. PMID- 1756424 TI - Force-interval relationship and its response to ryanodine in streptozotocin induced diabetic rats. AB - Post-quiescent potentiation (PQP), an enhanced contraction following a long pause that occurs as a result of increased Ca2+ release from intracellular stores, and post-stimulation potentiation (PSP), an enhanced contraction following a rapid series of contractions that is believed to be related to increased Ca2+ influx, were measured in streptozotocin-treated Wistar, spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) diabetic heart tissues. Decreased PQP values were found in Wistar and SHR diabetic papillary muscles (PM) in comparison with the same strain controls, which suggests a diminished degree of releasable Ca2+ from sarcoplasmic reticulum (SR) in these tissues. Decreased PSP was found in SHR diabetic PM, which may be related primarily to a depressed sarcolemmal (SL) Na(+)-Ca2+ exchange in this tissue. PSP was not decreased in diabetic Wistar or WKY cardiac preparations, indicating that Ca2+ entry via channels must be involved in the PSP mechanism. Ryanodine depressed PQP in Wistar and SHR PM, and SHR left atria in both control and diabetic tissues. It abolished PQP and SHR diabetic tissues but had no effect on WKY control and diabetic tissues. The data suggest that the ryanodine effect differs in the various strains of rat. These differences may be due to differences in the SR sensitivity to ryanodine among the strains. Diabetic SR with impaired Ca2+ uptake may contribute to these phenomena. Ryanodine depressed PSP of Wistar and SHR diabetic PM but had no effects on tissues from controls. The influence of ryanodine on diabetic SL Na(+)-Ca2+ exchange requires further investigation. PMID- 1756425 TI - Pharmacokinetic-hemodynamic studies of the enantiomers of isoidide dinitrate in conscious rats. AB - Our objective was to determine the pharmacokinetic properties of the D- and L enantiomers of isoidide dinitrate (IIDN) in relation to their hemodynamic effects. Conscious male Sprague-Dawley rats were administered a bolus i.v. dose of 2 mg.kg-1 D- or IIDN and simultaneous blood samples and blood pressure recordings were taken at various times. The elimination half-life of D-IIDN was significantly shorter than that of L-IIDN (10 vs. 16 min) owing to a larger Vd area of the L-enantiomer (5.8 vs. 3.8 L.kg-1). The plasma clearance of either enantiomer was approximately 250 mL.min-1.kg-1, a value equal to plasma cardiac output. The pharmacokinetic data indicates that IIDN is distributed extensively and that significant extrahepatic biotransformation of the drug occurs. After intravenous administration of D-IIDN, there was an initial decrease in mean arterial pressure (MAP) of 29% compared with 15% for L-IIDN (p less than 0.05). For L-IIDN, the decrease in MAP was short lived (less than 2 min), while for D IIDN, MAP remained significantly decreased for up to 60 min. The oral bioavailability of both enantiomers was low (ca. 7%). However, decreases in MAP occurred after oral administration of D-IIDN, suggesting that the mononitrate metabolite of IIDN was pharmacologically active. We conclude that, despite a faster rate of elimination from the central compartment, D-IIDN exhibits a greater vasodilator effect in the intact animal compared to L-IIDN. This is consistent with previous observations of a 10-fold greater potency of D-IIDN for relaxation of isolated vascular smooth muscle. PMID- 1756426 TI - Effects of the antiandrogen hydroxyflutamide on progesterone secretion by preovulatory rat follicles in vivo and in vitro. AB - Serum and ovarian progesterone levels and in vitro production of progesterone by preovulatory follicles were measured on proestrus in pregnant mare's serum gonadotropin (PMSG) primed immature rats in which the luteinizing hormone (LH) surge and ovulation were blocked by administration of the antiandrogen hydroxyflutamide. Serum progesterone levels observed at 12:00 on proestrus were significantly elevated, twofold above those observed in vehicle-treated controls, by in vivo administration of 5 mg hydroxyflutamide 4 h earlier. In control rats, proestrous progesterone did not increase until 16:00, in parallel with rising LH levels of the LH surge. No LH surge occurred in the hydroxyflutamide-treated rats, ovulation was blocked, and serum progesterone declined throughout the afternoon of proestrus, from the elevated levels present at 12:00. Administration of human chorionic gonadotropin (hCG) at 11:00 advanced the elevation of serum progesterone by 2 h in vehicle-treated controls and prevented the decline in progesterone levels in hydroxyflutamide-treated rats. The patterns of change in ovarian tissue concentrations with time and treatment were essentially similar to those observed for serum progesterone. In in vitro experiments, progesterone secretion during 24 h culture of preovulatory follicles obtained on PMSG-induced proestrus was significantly increased, sixfold, by addition to the culture media of 370 microM but not of 37 microM hydroxyflutamide. Testosterone (50 nM) and hCG (20 mIU/mL) caused 26- and 14-fold increases, respectively, in progesterone secretion by cultured follicles. Hydroxyflutamide significantly reduced the stimulatory effect of testosterone but not of hCG on progesterone secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756427 TI - Effect of low extracellular calcium and ryanodine on muscle contraction of the mouse during postnatal development. AB - We have examined the effects of low Ca2+ solutions, Co2+, and ryanodine on the isometric tension and contraction speed of isolated, developing mouse EDL muscles. Twitch responses of young muscles (7-14 days postnatal) were more sensitive to lowered [Ca2+]o than those of more fully developed muscles (22-35 days postnatal). Responses of EDL muscles from a middle-aged group (15-21 days postnatal) were intermediate between the two other groups. Overall, the time course of contraction in a single twitch was accelerated by low [Ca2+]o. Ca(2+) free solution induced a 7.95 and 9.25 mV depolarization in young and "old" muscle fibres, respectively. The presence of cobalt ions (5 mM) in the Krebs solution had a similar effect as Ca(2+)-free Krebs in terms of reduction of the isometric twitch and tetanic tensions of EDL muscles from the various age groups. In contrast, the shortening of the contraction time seen with Ca(2+)-free solution did not take place following exposure to Co(2+)-containing solutions. Finally, young (7-14 days postnatal) muscles were less sensitive to the inhibitory action of ryanodine on the twitch compared with more fully developed muscles (22-35 days postnatal). Taken together, our results indicate that from birth to maturity, there is a gradual change in the spectrum of calcium utilization for the contractile process. PMID- 1756428 TI - Pattern- and age-dependency of the antiepileptic effects induced by valproic acid in the rat hippocampus. AB - The effects induced by the antiepileptic drug valproic acid were studied in the CA3 subfield of in vitro hippocampal slices obtained from young (16- to 27-day old) and adult (over 60-day-old) rats. Spontaneous epileptiform discharges were induced by the addition of the convulsant 4-aminopyridine to the medium. Valproic acid (0.5 mM) selectively blocked the ictal epileptiform discharges in slices obtained from young rats. Interictal epileptiform discharges disappeared during perfusion with higher doses of valproic acid (2 mM). This blockade of interictal epileptiform activity was not observed when valproic acid (0.5-5 mM) was tested in hippocampal slices from adult rats. Thus, in the hippocampus of young rats, 4 aminopyridine-induced ictal activity is more sensitive to valproic acid than are interictal discharges. Moreover, valproic acid is effective in controlling interictal discharges in the young, but not in the adult rat hippocampus. PMID- 1756429 TI - Activation and function of prorenin: different viewpoints. Satellite symposium, 13th scientific meeting of the International Society of Hypertension, Montreal, Canada, June 22, 1990. PMID- 1756430 TI - Activation and function of prorenin: different viewpoints. AB - This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and its presence in extrarenal, as well as renal, tissues. Intriguing changes in plasma prorenin have been reported after treatment with antihypertensive and other drugs, following various physiological stimuli, and in pathophysiological states such as Wilms' tumor, Bartter's syndrome, and diabetic nephropathy. Lately, very high prorenin concentrations have been found in human and animal ocular fluid, ovarian follicular fluid, and in association with angiogenesis and microangiopathy. High circulating prorenin concentrations and fulminant hypertension have been reported in rats harbouring the mouse Ren-2 gene. However, what prorenin does in all these extrarenal fluids, tissues, and conditions is not well understood. Among the reasons for this lack of understanding are the difficulties in measuring prorenin and in establishing good animal models. We have not answered the critical question as to whether prorenin itself is bioactive like a hormone, and if so, what its action(s) might be. Nor have we established the main alternative, i.e., whether the function of prorenin is indirect, through renin--angiotensin, be it in the circulation or in the extrarenal tissues. This Symposium provides only partial methodological advances and answers, but we hope it will stimulate the breakthrough work needed to supply more complete answers. PMID- 1756431 TI - Trypsin activation of inactive renin: plasma blanks and angiotensin I radioimmunoassay. AB - Divergent conclusions exist as to whether inactive renin is present in nephrectomized rat plasma. A major factor contributing to this conflict may be related to significant changes in the "plasma blank" when trypsin-treated plasma is subjected to angiotensin I (AI) radioimmunoassay (RIA). In normal, but not nephrectomized rat plasma, AI-like substances are present in direct proportion to active renin. These substances are destroyed by trypsin. However, trypsin generates additional AI-like material, in both normal and nephrectomized rat plasma. This material, which is present in proportion to the renin substrate concentration, does not appear to be tetradecapeptide (TDP). In normal plasma, however, exogenous TDP is converted to AI in proportion to the active renin concentration and AI generation from TDP is increased by activation of inactive renin. However, in nephrectomized rat plasma, no AI generation from TDP was evident either before or after trypsin treatment. The coincident tryptic generation of a substance that quenches the levels of AI detected by RIA, combined with significant changes in the levels of endogenous and trypsin generated AI-like substances, may have significant bearing on the measured levels of inactive renin. PMID- 1756432 TI - Plasma active and inactive renin and fetal complications in women with high risk pregnancies. AB - To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it. PMID- 1756433 TI - Observations on the renal processing and sorting of prorenin. AB - Human prorenin is the biosynthetic precursor of renin. In general, prorenin is enzymatically inactive until it is converted to renin. The kidney is the major source of renin in the circulation, and is also an important source of circulating prorenin. The mechanisms of prorenin sorting and processing to renin in the juxtaglomerular cell may be a determinant of renal renin production. Therefore, our studies have focused on renal enzymes involved in "limited proteolysis" of prorenin to renin and on the morphology of prorenin sorting in the human juxtaglomerular cell. PMID- 1756434 TI - Activation and measurement of plasma prorenin in the rat. AB - Prorenin determination in rat plasma has been problematic from the outset. Consequently, its existence is questioned by some and its quantity by others, making it difficult for knowledge to advance as to its function relative to the renin system. The present study examines major variables in the determination of rat plasma prorenin and renin, notably different prorenin activation protocols involving blood samples obtained under various conditions from animals under different anesthetics. We found that a trypsin activation step with 5 mg/mL plasma, 60 min at 23 degrees C, followed by a PRA step of 10 min at 37 degrees C, resulted in the highest prorenin estimates, up to approximately 400 ng.mL-1.h-1 in terms of angiotensin I, as compared with published values of 0-190, based on other protocols. These estimates were obtained despite considerable destruction of angiotensinogen (renin substrate) by trypsin. Cryoactivation of prorenin was much less effective than in human plasma but, when followed by trypsin, it facilitated greater activation than with trypsin alone. Comparable fresh and fresh-frozen plasmas had similar prorenin-renin values, but lower values were observed in plasmas that had been repeatedly frozen and thawed. Conscious rats and those anesthetized with Inactin or ether had higher renins and prorenins than those anesthetized with methoxyflurane or halothane. Rats with kidneys in place during blood collection had higher renins (but not prorenins) than those whose kidneys were clamped off, suggesting that last-minute renin release during blood collection had occurred. We conclude that (i) trypsin generates increased renin, or renin-like, activity in plasma, suggesting activation of a precursor; (ii) on this basis, high prorenin levels exist in normal rat plasma; (iii) renin and prorenin levels are variously influenced by different anesthetics and blood handling procedures; (iv) variation in prorenin levels suggests that it is a dynamic (functional?) component of the renin system; (v) prorenin measurements are heavily influenced by methodological variations during the trypsin step or the subsequent PRA step; (vi) using standardized methodology, the rat can serve as a model for investigating the function of prorenin in normotension and hypertension. PMID- 1756435 TI - Investigation of human and rat inactive renin in plasma and kidney. AB - Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active and inactive renin were observed, suggesting activation of circulating inactive renin. Molecular weight (MW) studies revealed that this activation might proceed via a MW shift from inactive renin with MW of 50,000 to active renin of MW 43,000. In a later interval of stress, under stimulated renin secretion, a lower MW form (38,000) of active renin was released into the circulation. This MW is close to that of active renin (39,000) found in rat kidney renin granules. In renin granules, equilibrated in fractions of 1.6 and 1.7 mol/L sucrose in discontinuous density gradient, trypsin-activatable renin activity formed 36 and 16% of total activity, respectively. In humans, under acute bicycle exercise, a lower MW form (39,000) of active renin was released into the circulation, while the content of inactive renin with MW in the range of 51,000-58,000 and at 47,000 did not substantially change. There was a slight decrease in circulating inactive renin passing through the kidney. The data suggest that, at least in rats, in vivo pathways for activation of inactive renin might exist, other than that proceeding before secretion from renin granules. Under the conditions of increased renin secretion, a lower MW form of active renin is mainly released into the circulation in both rats and humans. PMID- 1756436 TI - Biochemical and immunological differences between plasma inactive renin from normal and nephrectomized rats. AB - Using immunological techniques, we have demonstrated that about half the trypsin activatable renin in normal rat plasma is prorenin, while the other is not, and that inactive renin in nephrectomized rat plasma is not prorenin. In the present study, the trypsin-induced angiotensin I generating activity not related to prorenin from normal rat plasma disappeared after HPLC on G3000SW. HPLC analysis of trypsin-treated plasma showed the generation of active renin by trypsin for normal rat plasma, while it did not for nephrectomized rat plasma. These results indicate that trypsin treatment of crude plasma results in the generation of angiotensin I generating activity not due to prorenin, as well as activation of prorenin. HPLC on G3000SW is a useful tool for the determination of plasma prorenin. PMID- 1756437 TI - Effect of prostaglandin inhibition by indomethacin on plasma active and inactive renin concentration in men. AB - The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (p = 0.004), total (p less than 0.001), and inactive (p = 0.02) renin at rest recumbent on average by 42, 19, and 8%, respectively, and at rest sitting on average by 45, 15, and 3%, respectively. Inhibition of prostaglandins with indomethacin reduced (p less than 0.001) active and total renin at each level of work load but not (p = 0.32) inactive renin. However, the exercise-induced stimulation (p less than 0.05) of active and total renin still occur during indomethacin. Indomethacin reduced (p less than 0.001) at rest sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2 by 50 and 54%, respectively, prostaglandin F2 alpha by 36 and 39%, respectively, and 13,14-dihydro-15-keto-prostaglandin F alpha by 38 and 60%, respectively. The urinary excretion of immunoreactive prostaglandin E2 and F2 alpha was also reduced. PMID- 1756438 TI - Does heparin inhibit renin activity? AB - Although heparin was reported in the 1960s to inhibit renin activity, this has not always been confirmed by other investigators. Hence, we re-examined whether heparin really inhibits renin or not. Renin activities were determined by radioimmunoassay of angiotensin I generated at pH 7.4. (i) No significant difference was found between the two kinds of plasma samples obtained with heparin and with EDTA as anticoagulant, in ARC (renin activity with addition of sheep renin substrate), TRC (ARC after activation of inactive renin by trypsin), or PRA (plasma renin activity without additional substrate). (ii) Even in higher concentrations of heparin up to 500 U/mL, neither PRA, ARC, nor TRC of plasma was affected significantly. (iii) Heparin, in concentrations up to 500 U/mL, exerted no significant effect on TRC of the media of human vascular smooth muscle cell culture. In conclusion, heparin does not exert any significant inhibitory effect on human renin nor does it affect activation of inactive renin by trypsin in the range of concentration of practical use, under the conditions employed in this study. PMID- 1756439 TI - Consistent activation of prorenin mRNA in renal hypertensive rats. AB - To investigate the mechanism of maintaining hypertension in chronic two-kidney, one-clip (2K1C) rats, we studied the expression of the kidney renin gene. Total cellular RNA was extracted by the guanidine thiocyanate--CsCl method. Kidney renin messenger RNA was quantified by densitometric Northern blot analysis using 32P-labeled rat renin genomic DNA as a hybridization probe. Sixteen weeks after clipping, plasma renin concentration and plasma angiotensin II concentration did not differ between 2K1C and sham-operated rats (plasma renin activity, sham rats 16.2 +/- 4.2 vs. 2K1C rats 8.9 +/- 1.3 ng angiotensin I.mL-1.h-1; plasma angiotensin II, sham rats 14.7 +/- 7.5 vs. 2K1C rats 6.8 +/- 1.3 pg/mL), while plasma angiotensin concentration in 2K1C rats was higher than that of sham rats (p less than 0.05). Renin gene expression in the ischemic kidney was 2.2 times higher than that in the kidney of sham-operated rats (p less than 0.05), and decreased to 80% of those in the kidneys of sham-operated rats. These results suggest that overexpression of the kidney renin gene in the chronic phases of 2K1C rats may contribute to the sustained high blood pressure, and the kidney renin gene may be inhibited by posttranscriptional factors, i.e., suppressed activation of prorenin to renin. PMID- 1756440 TI - Prorenin and gene activation. AB - After the discovery of an inactive, putative renin precursor that could be proteolytically activated, and the proteases involved in vivo, Morris and co workers directly demonstrated that renin is indeed synthesized as a "pro" form, and from genetic coding sequences they provided the structure of human prorenin. The gene is inactive and must be activated in prorenin-synthesizing tissues. To study the mechanism involved, we have performed transient expression analyses of putative regulatory DNA of the human gene (REN). 5'-Flanking DNA, extending from residue -144 to -2400, was linked to a reporter gene, viz. that for chloramphenicol acetyl transferase (CAT), and its ability to drive a heterologous (thymidine kinase, tk) promoter was examined by transfecting plasmid constructs into cells in culture and measuring CAT activity 48 h later. Because suitable renin-synthesizing cells were not available, choriocarcinoma (JEG-3) and cervical carcinoma (HeLa) cells were used. Although this DNA caused a reduction in CAT activity relative to the positive control, examination of a range of subfragments suggested that the -2400 to -144 region did not contain negative regulatory elements. In contrast, all fragments containing the -149 to +13 DNA segment gave CAT activities that were lower than the promoterless control. Together, the data were consistent with the presence of negative regulatory element(s) in that fragment of DNA that contained the REN promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756441 TI - Plasma active and acid-activatable renin during the development of one-kidney, one-clip and two-kidney, one-clip hypertension in the rabbit. AB - Systolic blood pressure in the central ear artery of eight rabbits increased by 21 mmHg (1 mmHg = 133.32 Pa) over 40 days following renal artery clipping and contralateral nephrectomy (one-kidney, one-clip). Plasma active and acid activatable (pH 2.8) renin did not change significantly. Similar data were obtained from a group of 12 rabbits following renal artery clipping alone (two kidney, one-clip) except that blood pressure in this group increased for 26 days but then declined until 40 days. Two animals with one-kidney, one-clip hypertension and three rabbits with two-kidney, one-clip hypertension had large increases in plasma active and inactive renin levels, which followed a more exaggerated rise in blood pressure than in the previous two groups. Forty days after unilateral renal artery clipping, the unclipped kidney was removed in 10 animals with two-kidney, one-clip hypertension. A further increase in blood pressure (+29%) occurred in seven of the animals but no change in plasma active or inactive renin. Results were compared with two groups of control animals, a unilateral nephrectomy group and a laparotomy group. None of the surgical procedures used produced a consistent pattern of change in the relative amounts of active and inactive renin in plasma. No marked changes in sodium, potassium, or water balance occurred in any group of animals. PMID- 1756442 TI - Measurement of inactive renin in normal, nephrectomized, and adrenalectomized rats. AB - In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues. PMID- 1756444 TI - Active and inactive renin in human forearm of hypertensive patients. AB - Although many in vitro and animal studies indicate the existence of a local renin -angiotensin system, data regarding its physiological role are quite controversial, and moreover, evidence suggesting inactive and active renin release from vascular tissue in vivo is lacking both in animal and humans. The aim of our study was to evaluate whether beta-adrenoceptor stimulation, a well known stimulus to renin production, through isoproterenol might cause local renin production from vessels of the forearm of hypertensive patients. Drugs were infused into the brachial artery at systemically ineffective rates, while forearm blood flow (FBF, venous plethysmography), mean intra-arterial pressure, and heart rate were monitored throughout. Active and inactive vessel renin production was measured by calculating venous-arterial (V-A) differences by simultaneous sampling from brachial artery and an ipsilateral deep vein. Active renin (PRA) and total renin (Sepharose bound trypsin activation) were measured by radioimmunoassay while inactive renin was calculated as the difference between total and active renin. V-A differences were corrected for FBF to calculate renin extraction or production. In a group of 10 patients, isoproterenol, which was infused at increasing cumulative rates (0.03, 0.1, 0.3 micrograms.100 mL-1 forearm tissue.min-1 for 5 min each), caused a dose-dependent increment in FBF that was blunted by intra-arterial propranolol (n = 5) pretreatment (10 micrograms.100 mL-1 forearm tissue.min-1 for 10 min). beta-Adrenoceptor stimulation caused a dose-dependent outflow of both active and inactive renin, an effect antagonized by propranolol. In conclusion, our data represent the first evidence in humans of tissue active and inactive renin production in the forearm vascular bed. PMID- 1756443 TI - Trypsin activation of human and cat prorenin: a comparative study. AB - Prorenin can be converted to renin by limited proteolysis with trypsin. In the current study we compared conditions for activation of human renal and ovarian prorenin and cat renal prorenin with either liquid-phase trypsin or trypsin bound to sepharose (solid phase). Higher concentrations of trypsin were required to activate cat prorenin than human prorenin. Human prorenin was destroyed by high concentrations of trypsin, while cat prorenin was not destroyed by up to 2 mg/mL solid-phase trypsin. For both human and cat prorenin, addition of the competitive serine protease inhibitor benzamidine--HCl increased the concentration of trypsin needed to activate prorenin, resulting in slightly higher levels of human prorenin but lower levels of cat prorenin. For human samples, activation with solid-phase trypsin resulted in slightly higher estimates of prorenin than liquid phase trypsin. These results demonstrate species differences in the susceptibility of prorenin to trypsin cleavage. Cat prorenin requires more trypsin to be activated and is less susceptible to destruction than human prorenin. PMID- 1756445 TI - Prorenin is present in human red blood cells. AB - We looked for the presence of prorenin in erythrocytes from normal subjects (n = 8), hypertensive patients (n = 8), and pregnant women (n = 8). Angiotensin I generation was measured at 37 degrees C, pH 5.7, in the presence of homologous substrate (1400 ng/mL) before and after trypsin activation (100 micrograms/mL) in (A) haemolyzed erythrocytes, (B) supernatants of haemolyzed erythrocytes, and (C) in the sixth washing of erythrocytes diluted 1:1 with a 0.1 M Tris buffer containing 0.5% bovine serum albumin and protease inhibitors. Haemolyzed erythrocytes generated angiotensin I only after trypsin treatment, and the rate of generation was the same (A) before and (B) after centrifugation at 20,000g, indicating the absence of prorenin bound to the cell membranes. When aliquots of the last washing of erythrocytes (C) were tested for angiotensin I generation before and after trypsin, they did not generate angiotensin I, indicating that residual prorenin from the plasma was no longer present in our preparation. Angiotensin I generation by trypsin-treated A and B was completely abolished by preincubation with anti-renin serum. The level of prorenin was not significantly different in the erythrocytes from normal, hypertensive, and pregnant subjects (68 +/- 10, 58 +/- 7 and 107 +/- 17 pg angiotensin I.mL-1.h-1, ns) in spite of their very different plasma levels (21 +/- 2.5, 17 +/- 2.4 and 110 +/- 12 ng angiotensin I.mL-1.h-1, p less than 0.01 for pregnant women compared with both normal and hypertensive subjects). Our data show that prorenin is present in human erythrocytes in fairly constant and clearly detectable amounts, thus suggesting a possible intracellular role for it. PMID- 1756446 TI - Animating the 3D structure and function of brain. AB - Three dimensional (3D) reconstructions of brain anatomy and physiology have greatly improved our understanding of complex spatial and densitometric relationships. The complexity and sophistication of these imaging techniques has steadily improved in the last few years and there are many situations in which the static display of 3D models contains more information than can be easily appreciated. Animating a sequence of these displays adds another dimension to the visualization, understanding and communication of 3D data. This paper describes those situations that warrant animations, the techniques necessary to compute them and the results that can be obtained. PMID- 1756447 TI - A densitometric method for quantitative analysis of the left ventricle performance using i.v. digital subtraction angiography. AB - In this paper we present a method we used to provide quantitative description of the systolic and diastolic temporal function of the left ventricle (LV). Additional parameters, such as peak filling and ejection rates, times to end systole and end diastole, and temporal changes in slow and fast filling are obtained. The volumes associated with these parameters are also calculated. Correlation between LV volume changes during the cardiac style and corresponding "density" variations was confirmed. Time-density curves were obtained from selected cardiac cycles in each study. We used the polynomial fitting technique to fit the time density curves and developed a computer algorithm for deriving the relevant parameters. Data from a total of 18 patients with ischemic heart or valvular diseases, who underwent I.V. ventriculography was analysed using our method. Some of these patients were forwarded for repeated digital subtraction angiography (DSA) examination before and after intervention therapy to evaluate the effectiveness of treatment. In comparison to the geometric method for the analysis of LV performance, our method is generally faster and simpler to employ. The method was effective in detecting variations in the peak ejection and filling rates in our group of patients before and after interventional therapy. PMID- 1756448 TI - Assessment of 99mTc-HM-PAO parameters with SPECT for improved evaluation of blood flow in cerebral lesions. AB - A method for investigating the linearity between blood flow and distribution of 99mTc-HM-PAO uptake in patients undergoing single photon emission computed tomography (SPECT) is presented. This method, based on particular elaboration techniques of sequential multiple acquisitions, provides a local index: cumulative transit time (CTT) related to all factors, other than blood flow, affecting 99mTc-HM-PAO uptake. Because a correct qualitative blood flow estimation is based on the uniformity of the above factors, the occurrence of a change of this index indicates a nonlinear relation between blood flow and 99mTc HM-PAO uptake distributions. It was shown that although linearity between blood flow and 99mTc-HM-PAO uptake may be questionable, a qualitative assessment of blood flow was correct in 100% of ischemic patients. In nonischemic patients this percentage fell to 60%. PMID- 1756449 TI - Multi-modality image combination: five techniques for simultaneous MR-SPECT display. AB - Increasingly, images are being acquired of the same patient using two or more diagnostic imaging modalities. If one such modality is MRI then a data set showing essentially anatomical information is produced. If the second is SPECT using HMPAO then a data set showing cerebral perfusion is also produced. The ability to conjoin such anatomical and functional data is an important goal in radiology. In this technical report five display strategies are investigated as a means of conveying simultaneously to the radiologist all the information from two such data sets. Illustrative examples are given for each display technique. Preliminary observations are made regarding comprehensibility, information loss and efficiency in conveying all the information simultaneously, for all five techniques. PMID- 1756450 TI - Thymic cyst secondary to cervical irradiation: a complication of treated laryngeal cancer. AB - This report demonstrates a thymic cyst arising in association with cervical irradiation for laryngeal carcinoma; a process not previously described. Thymic cysts are rare anterior mediastinal masses which have many etiologies, though an increased incidence of thymic cysts in association with Hodgkin's disease has been reported. This association was thought to be related to either mediastinal irradiation or cystic changes within a thymic focus of Hodgkin's disease. This case supports the theory that at least some thymic cysts arise secondary to irradiation. PMID- 1756451 TI - The MR equivalents of cerebral hemispheric disconnection: a telencephalic commissuropathy. AB - Since the original observations of cerebral disconnection in experimental conditions with animal models, the surgical division of the cerebral commissures for control of seizure activity has led to the description of a human hemispheric disconnection syndrome. More recently, MR has revealed a spectrum of conditions of the forebrain responsible for the natural development and acquired occurrence of this unique commissural syndrome. Acutely, nonspecific expressions of disconnection may be observed; however, there are no explicit behavioral manifestations of this syndrome in the chronic state. The signs of stabilized hemispheric disconnection are only elicitable via sophisticated, neuropsychological testing performed by experienced technicians. Included in the present series of callosal pathology were individuals with agenesis, surgical section, infarction, trauma, glioma, and Marchiafava-Bignami disease. On specialized examination, the surgical "split-brain" patients illustrated the classic syndrome of a halt of interhemispheric transfer of information, a block of nondominant hemisphere access to language functions and an inhibition of dominant hemisphere access to superior visuospatial capacity. The nonsurgical subjects with developmental callosal agenesis and acquired pathologic processes involving the callosum revealed a varied, nonspecific reduction in cognitive function most probably related to associated extracallosal hemispheric pathology. No external abnormalities in behavior which could be attributed specifically to the callosal findings were identified chronically, although some progressive diseases suggested the presence of a subacute symptomatic phase of the disconnection syndrome. Any condition which causes the division, destructive insult, or primary ontogenic nondecussation of commissural axons will produce an interference in interhemispheric, interneuronal communication. This is manifested by individual degrees of covert interhemispheric data transfer arrest and of reduced bidirectional dominant-nondominant hemispheric access and telencephalic integrative capacity, consistent with a cerebral commissuropathy. This study reveals the MR equivalents of the hemispheric disconnection syndrome which occur in many nonspecific pathologic conditions of the cerebrum, but which result in few if any overt behavioral aberrations in the stabilized state. PMID- 1756452 TI - MR of hemorrhagic acoustic neuromas. AB - The magnetic resonance (MR) appearance of hemorrhagic acoustic neuromas has not previously been reported. Four patients with surgically proven acoustic neuromas containing spontaneous hemorrhage were preoperatively evaluated with MR imaging. All patients presented with new onset of symptoms and three had subarachnoid hemorrhage. Signal changes on T1- and T2-weighted spin echo sequences were characteristic for acute, subacute and chronic intraparenchymal hemorrhage. Recognition of hemorrhagic changes on MR is important since more rapid surgical intervention is required in this patient subgroup. PMID- 1756453 TI - Increased signal intensity of T1-weighted MR image of physiologic intracranial calcifications. AB - Among 1500 MR studies of the brain, performed during 1 year, there were six cases of physiologic calcifications (four in the falx cerebri, two in the deep gray matter) that revealed high signal intensity on T1- and variable signal on T2 weighted images. This phenomenon should be recognized and not confused with entities of clinical significance especially hemorrhage. PMID- 1756454 TI - Computerized tomographic findings in two cases of congenital fibrosis syndrome. AB - Two patients with congenital ptosis and extraocular muscle fibrosis are described. The first patient showed marked atrophy of the left inferior rectus muscle. The second patient showed bilateral changes in all extraocular muscles. Computed tomographic evaluation of the extraocular muscles was performed in both patients. The characteristic changes of this phenomenon were seen in both individuals and solidified the diagnosis. PMID- 1756455 TI - Computed tomography of odontogenic keratocysts. AB - Epithelium-lined cysts of the jaw can be either odontogenic or non-odontogenic. Cysts that exhibit keratinization of their epithelial lining are called odontogenic keratocysts. They compose approximately 8% of all odontogenic cysts. There is a frequent association with unerrupted teeth, and a high incidence of occurrence of keratocysts in the multiple basal cell nevus syndrome. The significance of odontogenic keratocysts is their high potential for recurrence after their removal. There is no specific radiographic feature, however, that distinguishes them from non-keratinized odontogenic cysts. High resolution computed tomography (CT) studies can exquisitely determine the extent of these lesions and pinpoint areas of cortical breakthrough as well as involvement of the teeth. This information is invaluable in surgical planning for excision of these lesions. PMID- 1756456 TI - Abdominal computed tomography in lupus mesenteric arteritis. AB - We report the abdominal computed tomography (CT) findings in a patient with systemic lupus erythematosus who developed signs of an acute abdomen secondary to mesenteric arteritis. Initial CT scan demonstrated ascites and wall thickening of the duodenum and jejunum. After treatment with high dose intravenous steroids, follow-up CT scan demonstrated a normal duodenum and small bowel. This is the first surgically proven case of lupus mesenteric arteritis resulting in bowel ischemia that is demonstrated on CT before and after medical therapy. Lupus mesenteric arteritis should be included in the differential diagnosis of causes of bowel wall thickening and ischemia, especially if mesenteric vessels appear prominent. PMID- 1756457 TI - Pathologic vertebral compression in spinal malignancy secondary to intervertebral disk expansion. AB - A retrospective analysis of the MR appearance of the intervertebral disks in 17 patients with spinal malignancy was performed. Disk expansion, related to neoplastic structural weakening of the bone in the face of unaltered disk biomechanics, was present in 20% of all visualized disks in association with a 77% incidence of malignant involvement of the vertebral bodies studied. This compared with a frequency in benign disk expansion (i.e., osteoporosis) of 2% in the age-matched, but randomly selected, control group. On careful review, there was no strict correlation between disk expansion and patient symptoms. Although this finding may be seen in non-neoplastic conditions, it is felt that the higher incidence of disk expansion associated with osseous vertebral malignancy nevertheless reflects the underlying gravity of the pathologic changes accompanying neoplasia. PMID- 1756458 TI - The cytogenetics of ataxia telangiectasia. AB - Ataxia-telangiectasia (AT) is a heterogeneous autosomal recessive disorder marked by cerebellar ataxia, oculocutaneous telangiectases, hypersensitivity to ionizing radiation, immunodeficiency, and cancer susceptibility. AT is also a spontaneous chromosomal breakage syndrome, notable for tissue-specific cytogenetic changes and telomeric fusions. Molecular characterization of rearrangements specific to T lymphocytes suggests that a DNA repair/processing defect is potentially responsible for the diverse array of chromosomal abnormalities observed in a variety of AT cell types. PMID- 1756459 TI - Fragile 3p14 in patients with von Hippel-Lindau syndrome compared to controls. AB - Lymphocytes from a series of ten patients with von Hippel-Lindau syndrome have been cultured under conditions designed to demonstrate the presence of fragile sites. Compared to a series of controls the subjects with von Hippel-Lindau syndrome show a small but significant increase in the level of FRA3B. PMID- 1756460 TI - Chromosome abnormalities of porokeratosis-cultured epidermal keratinocytes. Comparison with those of cultured dermal fibroblasts. AB - Cultured epidermal keratinocytes and dermal fibroblasts derived from porokeratosis (PK) patients' skin lesions or normal-appearing skin had numerical and sometimes structural chromosomal abnormalities. Such abnormal cells were seen in 4.08% and 0.375% of all the studied epidermal keratinocytes derived from affected skin and normal-appearing skin, respectively. Similar abnormalities were present in 1.70% and 3.67% of the dermal fibroblasts from the patients' affected skin and normal-appearing skin, respectively. Chromosomal abnormalities were more frequent in keratinocytes and fibroblasts from the patients' skin than in keratinocytes (0.429%) or in fibroblasts (1.22%) derived from normal control donors. Clonal proliferation of such abnormal cells was frequently seen in keratinocytes from the patients' affected skin. The frequent appearance of chromosomal abnormalities and clonal proliferation in epidermal keratinocytes may explain skin lesion formation and skin cancer development in PK patients. PMID- 1756461 TI - Translocation (4;14) and concomitant inv(14) in a basal cell carcinoma. AB - Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4;14) (p14;p11) and a concomitant inversion of the same chromosome 4 involved in the t(4;14) with the breakpoints at p14 and q25. PMID- 1756462 TI - Cytogenetic analysis of head and neck carcinomas. AB - Ten primary squamous cell carcinomas (SCC) of the head and neck were evaluated cytogenetically after 10-14 days of in vitro culture. Addition of 3% L-glutamine was essential for consistent epithelial growth of these carcinomas. Outgrowth of cells from tissue explants contained a mixture of chromosomally normal and abnormal cells; the abnormal cells had extensive changes including translocations, marker chromosomes, inversions, deletions, and duplications. In addition, all carcinomas contained cells with pulverization and double minute chromosomes (dmin). Chromosomes 11, 13, and 14 had "hotspots" of rearrangements. PMID- 1756463 TI - Pure red cell aplasia in a case of Ph negative BCR/ABL rearranged CML with t(12;14)(q23;p11). AB - A patient with chronic myelogenous leukemia (CML) associated with pure red cell aplasia (PRCA) is reported. The occurrence of PRCA has been described previously in sporadic cases of Philadelphia chromosome (Ph) positive CML. In this patient, however, the Ph-chromosome was not detected; cytogenetic analysis revealed a t(12;14)(q23;p11) as the sole abnormality. Molecular studies by Southern and PCR analyses showed the rearrangement of the BCR and ABL sequences and expression of the chimeric bcr/abl mRNA, thus confirming the diagnosis of CML. To our knowledge, this is the first report on a case of PRCA associated with Ph negative CML at diagnosis. The possible connection between CML and PRCA is discussed. PMID- 1756464 TI - Cytogenetic analysis of two sacral chordomas. AB - Cytogenetic analysis of two sacral chordomas revealed two distinct abnormal clones in one of the cases: 44,XY,t(1;3)(q42;q11), -2,der(7)t(2;7)(q23;q32), -21 and 46,X,t(Y;8)(q12;q22), t(1;14)(p34;q32),t(5;10)(q13;p11). All cells analyzed from the second case were cytogenetically normal. To the best of our knowledge, chordomas have not previously been subjected to cytogenetic analysis. PMID- 1756465 TI - In vitro bone marrow cell culture and cytogenetic analysis in a case of myelodysplasia. AB - A case of refractory anemia with sideroblastosis and a number of bone-marrow blasts slightly over the limit which separates the I/II and III FAB-subtypes of myelodysplastic syndromes is described. The leukemic-like type of in vitro growth and the multiple karyotypic changes observed in the bone-marrow cells at presentation were both indicators of the malignant nature of the disorder and underlined the importance of these studies in assessing diagnosis and prognosis in patients with preleukemic disorders. The role that the chromosome aberrations, del(11)(q14) and del(18)(q21), both found in 100% of the bone-marrow metaphases examined, may play in the pathogenesis of the disease is also discussed. PMID- 1756466 TI - Specific chromosomal defects associated with metastatic potential in K-1735 melanoma clones. Involvement of chromosomes 4 and 14. AB - In this study we sought to identify specific cytogenetic defects associated with the metastatic phenotypes in clones isolated from the parental K-1735 murine melanoma. All nonmetastatic clones (C-3, C-10, and C-19) exhibited trisomy of chromosomes 1, 3, 12, and 15. The only structural defect present in these clones was an interstitial deletion in a chromosome 4. In contrast, the highly metastatic clones (C-4, M-2, BB1, and X-21) exhibited trisomy of chromosomes 1, 3, 12, and 15, plus structural abnormalities of chromosomes 4 and 14, with the net result of a deletion in both. Parental K-1735 cells and clone C-16 cells, which are intermediate in their metastatic potential, had some cells with 4 and 14 alterations and others with only a deletion of chromosome 4. Clone C-16 revealed other non-clonal structural abnormalities. Our results indicate that structural anomaly of chromosome 4 and numerical alterations of certain autosomes may be associated with tumorigenic properties. In addition, structural defect in chromosome 14 is associated with high metastatic potential of K-1735 melanoma cells. PMID- 1756467 TI - "Jumping translocation" in a 17-month-old child with mixed-lineage leukemia. AB - A 17-month-old child with acute biphenotypic (pre B-ALL/myelomonocytic) leukemia is reported. Extensive cytogenetic analysis performed at various stages of the disease revealed a clonal evolution at the time of initial diagnosis with two types of abnormal clones, one with trisomy 22 and two other related clones with trisomy 22 plus partial trisomy of the long arm of chromosome 1 associated with the telomeric segment of either chromosome 20q or 21p. At the time of relapse the only abnormal clone involved trisomy 22 and partial trisomy of 1q, but this time in association with the telomeric segment of 14p. The unique feature of these translocations is discussed and the possibility of the correlation between the different chromosomal abnormalities and the expression of biphenotypic markers is raised. PMID- 1756468 TI - Cytogenetics of six follicular thyroid adenomas including a case report of an oxyphil variant with t(8;14)(q13;q24.1). AB - Cytogenetic analyses were performed on six follicular thyroid adenomas. Five had normal karyotypes and one, an oxyphil adenoma, had a t(8;14)(q13;q24.1). This patient also had a history of pleomorphic adenoma of the parotid gland. This clonal abnormality may suggest a primary genetic lesion in this patient who had two different benign neoplasms. PMID- 1756469 TI - Acute monoblastic leukemia (FAB-M5b) with t(8;14)(p11;q11.1). AB - A case of acute monocytic leukemia (FAB-M5b) expressing natural killer cell associated antigens containing a t(8;14)(p11;q11.1) is presented. We interpret this translocation to represent a variant of the t(8;16) previously reported in FAB-M5b. These findings support the contention that the 8p11 breakpoint site is the critical junction in the oncogenesis of acute monoblastic leukemia with differentiation. PMID- 1756470 TI - Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes? AB - Cytogenetic and clinical data of 11 patients with de novo myelodysplastic syndromes and partial or total trisomy of the long arm of chromosome 1 are presented. In eight of these patients trisomy 1q was the sole karyotypic change and therefore can be classified as a primary chromosome anomaly. A remarkably young median age of 36.5 years was noticed in this patient group. PMID- 1756471 TI - A rare translocation (4;11)(q21;p14-15) in an acute lymphoblastic leukemia expressing T-cell and myeloid markers. AB - A 21-year-old male presented with a large mediastinal mass and a white cell count of 420 x 10(9)/L. A diagnosis of acute lymphoblastic leukemia (ALL) was made, with 90% of cells in the bone marrow (BM) and 99% in the peripheral blood (PB) being lymphoblasts (FAB L1). Cytogenetic analysis of these cells revealed a rare variant of the t(4;11) translocation involving chromosome arm 11p rather than 11q, namely t(4;11)(q21;p14-15). The standard form of the (4;11) translocation has been associated with leukemias with mixed-lineage phenotypes. Three cases of ALL with t(4q;11p) have previously been reported. One of these cases showed phenotypic heterogeneity involving myeloid and lymphoid lineages. The leukemia reported here also exhibits lymphoid/myeloid features. Immunophenotyping of the blasts showed that most of the cells were positive for CD2, CD5, CD7, CD10 (CALLA), CD34, and HLA-DR. A significant proportion of the cells expressed CD33. These results suggest a biphenotypic rather than a biclonal disease. Molecular analysis showed rearrangement of both immunoglobulin heavy-chain genes (JH) and of a single allele of the T-cell receptor (TCR) gamma 1 gene, while retaining germline TCR beta genes. PMID- 1756472 TI - Telomeric associations and consistent growth factor overexpression detected in giant cell tumor of bone. AB - Tumor specimens from 15 patients with giant cell tumor (GCT) of bone were cytogenetically analyzed. A subset of five individuals had tumor cells harvested and polyadenylated RNA isolated. Multiple Northern blots were performed utilizing radiolabeled probes for the growth factors TGF beta 1, TGF beta 2, TGF beta 3, and TGF alpha (TGF, transforming growth factor). RNAs from other types of neoplasms and nonneoplastic cells were examined as controls. The most consistent cytogenetic abnormality detected involved multiple telomeric associations (TAs), most frequently involving the terminus of the long arm of chromosome 19 (19q). Northern blot analysis revealed a consistent expression of TGF beta 1 and TGF beta 2 with an inconsistent mRNA expression for the other TGFs. There was a relative overexpression of mRNA for TGF beta 2. The gene location for TGF beta 1 is near the 19q terminus and thus it is speculated that TGF beta may play a role in the neoplastic transformation of GCT. PMID- 1756473 TI - Deletion of part of the long arm of chromosome 13 as the only karyotypic aberration in a follicular thyroid adenoma. AB - A follicular thyroid adenoma is described showing a del(13)(q14) as the only karyotypicabnormality. The karyotypic similarities to another benign tumor, the lipoma, are discussed. PMID- 1756474 TI - Translocation (2;16)(p11;q22) and trisomy 22 in acute myelogenous leukemia (FAB M2) with bone marrow eosinophilia. PMID- 1756475 TI - Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition. AB - We showed previously that the persistence of chromatid breaks and gaps after G2 phase irradiation with X-rays or near-UV visible light characterizes skin fibroblasts from individuals with cancer-prone genetic diseases. This abnormal response appears to result from deficient DNA repair during G2 and to be associated with cancer proneness. We have, therefore, compared the responses of cells from two genetic disorders, Cockayne syndrome (CS) and xeroderma pigmentosum complementation group C(XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either X-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. This deficient repair in the presence of DNA damage and continuous cell cycling from activation of proto-oncogenes or loss of suppressor genes may be necessary and sufficient for cancer development. PMID- 1756476 TI - Translocation (8;21) in acute nonlymphocytic leukemia delineated by chromosomal in situ suppression hybridization. AB - In situ suppression hybridization with recombinant bacteriophage DNA libraries for chromosomes 8 and 21 was performed in two cases of acute nonlymphocytic leukemia, type FAB M2. In both cases, cytogenetic analysis by conventional G banding revealed t(8;21)(q22;q22). In situ suppression hybridization was able to prove the reciprocal nature of the translocation in both cases by identifying the terminal end of chromosome 21 translocated to the derivative chromosome 8q-. PMID- 1756477 TI - DNA sequences of chromosome 21-specific YAC detect the t(8;21) breakpoint of acute myelogenous leukemia. AB - The t(8;21)(q22;q22) is a nonrandom translocation specifically marking blasts of acute myelogenous leukemia (AML) with undifferentiated phenotype. The breakpoint on chromosome 21 involved by this rearrangement has been precisely localized relative to cloned DNA markers by physical and genetic linkage analysis enabling the use of positional cloning for its isolation. Yeast artificial chromosome (YAC) clones for loci proximal (D21S65) and distal (ERG) to the (21q22) breakpoint have been developed and their chromosome 21 origin and location relative to the breakpoint has been established. By using in situ hybridization analysis, a 240 kb YAC clone for the D21S65 locus clearly identified both derivative chromosomes of the (8;21) translocation in metaphase spreads of leukemia blasts with the rearrangement. The characterization of the DNA sequences contained in this 240 kb YAC can reveal the functional consequences of their derangement in leukemia with abnormalities of the (21q22) region. PMID- 1756478 TI - Clonal chromosome abnormalities and in vitro growth characteristics of classical and cellular schwannomas. AB - Cytogenetic analysis was performed on 12 schwannomas, 10 classical and two of the cellular type. Electron microscopic examination of cultured cells from two classical and two cellular schwannomas revealed features compatible with a Schwann cell differentiation. Immunohistochemical analysis of the cultures demonstrated immunoreactivity for S-100 protein in 6 of 6 cases and for vimentin in 2 of 2 cases of classical schwannoma, thus further supporting the authenticity of the cultured cells. Cultured cells from one cellular schwannoma also exhibited immunoreactivity for glial fibrillary acid protein (GFAP). Cytogenetic analysis of the 12 tumors revealed clonal abnormalities in 10 of the cases. In the majority of tumors, cells with a normal karyotype coexisted with different abnormal clones and sporadic deviations. Numerical changes predominated and were found in all tumors, while structural rearrangements were detected in eight tumors. The most common abnormality was clonal or sporadic loss of chromosome 22, which was found in all cases. Other clonal abnormalities included loss of one sex chromosome found in five cases, -15 found in three cases, and -12, +5, +7, +20 found in two cases each. These results provide further evidence in support of a role for loss of chromosome 22 in the pathogenesis of schwannomas. Our findings also indicate that there exist several different evolutionary pathways for schwannomas, and that some of these are shared by several other types of benign and malignant tumors of the nervous system. PMID- 1756479 TI - Trisomy 8 in primary esthesioneuroblastoma. AB - Esthesioneuroblastoma is a rare malignancy believed to be derived from neuroectodermal stem cells within the olfactory epithelium. We have obtained the karyotype of a primary esthesioneuroblastoma following brief (7-day) in vitro culture, and have determined that the only observable cytogenetic anomaly is the presence of an additional chromosome 8. Previously, the karyotypes of two cell lines established from metastatic esthesioneuroblastomas have been reported to contain the equivalent of three copies of chromosome 8, in addition to other chromosomal aberrations, including the reciprocal translocation, t(11;22)(q24;q12). Examination of the cytogenetic literature suggests that an extra copy of chromosome 8 is a common occurrence in undifferentiated small round cell tumors frequently observed to carry the t(11;22), including esthesioneuroblastoma, Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and rhabdomyosarcoma. These data, combined with our report of a small round cell tumor with the karyotype 47,XY, +8, indicate that trisomy 8 may be a common phenomenon in these tumors, and may also provide some sort of selective advantage to these tumor types. PMID- 1756480 TI - Renal cell carcinoma in a child. PMID- 1756481 TI - Philadelphia chromosome positive chronic myelocytic leukemia with a complex translocation, t(4;9;22)(q31;q34;q11) and long survival. PMID- 1756482 TI - Establishment and characterization of a new Ewing's sarcoma cell line. AB - A new human Ewing's sarcoma cell line (CADO-ES1) was established from the malignant pleural effusion of a 19-year-old woman. These cells grew both anchorage dependently and anchorage independently. When cultured in bacteriologic dishes, they grew as tightly packed multicellular tumor spheroids; they were also capable of proliferating in soft agar. Flow cytometric DNA analysis demonstrated a nearly diploid DNA content (DNA index = 0.902). Chromosomal studies of cultured cells showed an isodicentric chromosome 8 in all examined cells, but t(11;22)(q24;q12), a translocation reported previously in Ewing's sarcoma, was not detected. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. In addition, immunocytochemical studies showed that vimentin was intensely positive, whereas neurofilament (NF) and neuron-specific enolase (NSE) were weakly positive. Treatment with cyclic AMP (cAMP) induced pronounced morphologic evidence of neural differentiation and strong expression of NF in cultured cells. S-100 protein, glial fibrillary acidic protein (GFAP), desmin, cytokeratin, and epithelial membrane antigen were not detected immunohistochemically in either untreated or cAMP-treated cells, however. These data suggest that this cell line is derived from a highly undifferentiated neural cell with high chromosomal clonality, differentiating into neural features under certain conditions. PMID- 1756483 TI - Karyotyping of a hematologic neoplasia developing shortly after treatment for cerebral extragonadal germ cell tumor. AB - Hematologic malignancies may be associated with mediastinal extragonadal germ cell tumors. It may be that the hematologic malignancy is a part of the natural history of the teratoma, one germ cell tumor line being able to differentiate into hematological cells, or the hematologic malignancy is related to the treatment, or the two malignancies develop independently. Cytogenetic analysis of bone marrow from a patient with a germ cell tumor in the brain and the almost simultaneous appearance of a hematologic neoplasia showed a rearranged karyotype in that all 15 analyzed cells had the same karyotype: 50,XY, +X, +del(1)(p21), +10, +11, -12, +der(12)t(12;?)(q?;?). Our findings were consistent with the interpretation that the hematologic malignancy was derived from the germ cell tumor. PMID- 1756484 TI - Lymphoblastic lymphoma with primary splenic involvement and the classic 14;18 translocation. AB - Clinicopathologic features of a case of lymphoblastic lymphoma (LyL) with the classic 14;18 translocation are described in this article. The patient had prominent splenomegaly with numerous splenic nodules, exhibiting a homogeneous blast cell infiltrate and occasional cells with cleft nuclei, a picture suggestive of high-grade non-Hodgkin lymphoma (NHL) possibly lymphoblastic. Early B-cell features were detected immunologically, thus confirming the diagnosis of LyL. The presence of primary splenic involvement and of the t(14;18)(q32;q21) are unusual in this histologic subset of B-cell NHL, these cytogenetic and clinicopathologic characteristics being typically associated with low- or intermediate-grade NHL of follicle center origin. These features, along with the presence of some centrocytelike cells in the biopsy sections, suggest that an unusual pattern of histologic evolution from a follicle center cell NHL may have occurred in this case of LyL. PMID- 1756485 TI - Second relapse of acute promyelocytic leukemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21). AB - We describe herein a patient with acute promyelocytic leukemia (APL)-(ANLL-M3) whose bone marrow cells in the second relapse showed t(1;3)(p36;q21) together with t(15;17) (q22;q11-q12). Although a total of 21 patients with t(1;3) have been reported so far, among which three cases with de novo acute nonlymphocytic leukemia were included, our patient is the first case with APL. The hematologic findings in our case confirmed the previous observations that this anomaly is associated with relatively high platelet count and the multi-myeloid lineage involvement of leukemic cells. Our patient responded well to chemotherapy and achieved first and second remission with 42 months of total survival, contrary to our expectation that patients with this anomaly have a poor prognosis. PMID- 1756486 TI - Cytogenetic analysis of the mature and immature teratoma components of a metastatic testicular nonseminomatous germ cell tumor. AB - A case is described in which the mature and immature teratoma components of metastases of the same testicular nonseminomatous germ cell tumor were karyotyped. The highly similar karyotypes of both components suggest that the phenotypic difference is predominantly epigenetically determined. PMID- 1756487 TI - Karyotype evolution of Ph positive chronic myelogenous leukemia patients relapsed in advanced phases of the disease after allogeneic bone marrow transplantation. AB - Sixty-eight patients affected by Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) and were successfully studied from a cytogenetic point of view, before and after the BMT. Nineteen had evidence of cytogenetic and clinical relapse. Cytogenetic analyses of 14 patients who, after the relapse, showed progression to the accelerated or blastic phase of the disease, are presented. Five of these cases had only the Ph chromosome without karyotype evolution; in one case Ph duplication without other anomalies was detected, while in the remaining eight cases cytogenetic analysis showed apparently random clonal structural abnormalities (translocations, inversions, deletions, and marker formations). Therefore, the classical "non-random" abnormalities (+8, i(17q), +Ph, +19, +21) were not as common as in conventionally treated Ph+ CML. From our data, karyotype evolution during advanced phases in Ph+ CML patients after BMT differs from the evolution seen in conventionally treated patients, by the presence of numerous structural unusual abnormalities, possibly related to radiochemotherapy conditioning to BMT. Therefore, BMT treatment is not always able to eradicate the Ph+ clone but can reduce the incidence of the formation and/or expansion of Ph+ clones with additional non-random abnormalities. PMID- 1756488 TI - Trisomy 13: a preferentially male chromosome aberration interfering specifically with myeloid proliferation and differentiation? Report of a case and review of the literature. AB - A case of trisomy 13 is presented: a 73-year-old man with acute nonlymphocytic leukemia (ANLL), FAB borderline M1/M2, and peripheral leukocyte and platelet counts that were difficult to control with chemotherapy. A literature review shows that 35 cases of trisomy 13 are known at present. They are characterized by male predominance (76%), preferentially myeloid disorders (ANLL, myelodysplastic syndromes, chronic myeloid leukemia), leucocytosis, and relatively high platelet counts and hemoglobins. It is suggested that trisomy 13 is a specific nosologic entity with male predominance and characterized by interference with proliferation and differentiation in the myeloid differentiation series. PMID- 1756489 TI - Significance of chromosomal abnormalities in a malignant giant cell tumor of bone. AB - Cytogenetic analysis of a malignant giant cell tumor of the sacrum from a 62-year old female revealed the following chromosomal complement: 47,XX, -1, -11, +22,del(2)(p22),t(7;7) (p22;q32), +der(1)t(1;11;21)(p32;q13;q22), +der(19)t(19;?)(q13.4;?), der(8)t(8;?)(p11;?), der(7)t(17;?)(p13;?). Metaphase cells with 92-127 chromosomes sharing identical structural abnormalities detected in the near-diploid cells were also observed. Several of these abnormalities have previously been described in the benign giant cell tumors supporting a direct relationship between these benign and malignant neoplastic counterparts. PMID- 1756490 TI - Simultaneous analysis of chromosomal aneusomy and 5-bromodeoxyuridine incorporation in MCF-7 breast tumor cell line. AB - We describe a new method to determine simultaneously both proliferative status and chromosome copy number within individual interphase cells. The MCF-7 human breast cancer cell line was used as a model system to characterize proliferative activity in karyotypically defined cell subpopulations. Cells were labeled with bromodeoxyuridine (BrdU) in vitro and incorporation was monitored with IU4 mouse anti-BrdU. Biotinylated, digoxigenin-labeled, or acetylamino-fluorene-conjugated repetitive sequence DNA probes were hybridized to target interphase nuclei. Three color fluorescence labeling allowed simultaneous detection of two chromosome pairs and designation of cells undergoing DNA synthesis. This technique may also be used for simultaneous characterization of proliferative and karyotypic heterogeneity in primary human tumors. PMID- 1756491 TI - Complex chromosomal translocations in the Philadelphia chromosome leukemias. Serial translocations or a concerted genomic rearrangement? AB - Joining of the BCR and ABL genes is an essential feature of the group of human leukemias characterized by the Philadelphia chromosome and there is recent evidence that the human BCR-ABL fusion gene induces leukemia in experimental animals. Joining of these two genes is the result of cytogenetic translocation, usually the t(9;22)(q34;q11), but sometimes of more complex translocations involving one or more chromosomes in addition to chromosomes 9 and 22. The leukemic cells of some patients carry the BCR-ABL fusion gene but have an apparently normal karyotype. Recent studies show that these cells conceal complex chromosome rearrangements. Because the BCR-ABL fusion gene appears to be the result of cytogenetic rearrangement in all cases of these leukemias, the causes and mechanism of chromosome rearrangement will be relevant to the development of leukemia in man. We examine mechanisms of chromosome rearrangement and propose that both simple and complex chromosome translocations result from a single, though sometimes complex, interchange event. PMID- 1756492 TI - Translocation (3;21) characterizes crises in myeloid stem cell disorders. AB - Three patients, one with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia (CML) and two with primary acquired myelodysplastic syndromes (MDS), have been identified to have a t(3;21)(q26;q22). In the patient with CML, the t(3;21) was detected only in the blast phase. The t(3;21) as the sole abnormality appeared at presentation of MDS [refractory anemia with excess blasts (RAEB)] in one patient and remained as such when progression to RAEB in transformation (RAEB t) occurred. The other patient with MDS had the t(3;21), in addition to other changes, during the progression of the disease. Thus, t(3;21) may characterize myeloid crises of clonal hematopoietic stem cell disorders (HSCD) and indicates a poor prognosis. As a primary cytogenetic event it may be also involved in the genesis of myelodysplasia with subsequent leukemic transformation. PMID- 1756493 TI - Chromosomal abnormalities in giant cell tumors of bone. AB - Cytogenetic analysis of short-term cultures from ten giant cell tumors of bone revealed clonal and nonclonal chromosome abnormalities in three tumors and nonclonal changes only in seven. None of the clonal aberrations, inv(21)(p11q21) in one tumor, +5 in another, and t(15q22q), dic(4;22)(p16;p1?), double minutes, dicentrics, and ring chromosomes present in three separate clones in the third tumor, were identical to previously reported clonal changes in giant cell tumors. Telomeric associations were found in five tumors. The telomeres of chromosome arms 19q and 15p were particularly frequently involved. PMID- 1756494 TI - Atypical (7;19) translocation in acute myelomonocytic leukemia. AB - Chromosome studies were carried out after a 24-hour harvest of unstimulated bone marrow aspirate cell cultures from a 75-year-old male with a clinical diagnosis of acute myelomonocytic leukemia (FAB M4). Analysis of nine cells after trypsin Giemsa banding (GTG) revealed two cell lines with a mosaic chromosome pattern, 46,XY/46,XY,t(7;19)(q22;p13.3). A review of the recent literature reveals one case of childhood ALL with a 46,XY/46,XY,t(7;19)(q11;q13) chromosome pattern [1] and a 46,XY,t(3q;11q),t(7q;19p),t(15;17)(q26;q22) in one patient with ANLL (FAB M3) [2]. The t(7;19)(q22;p13.3) seen in our case has not been reported as the sole specific clonal chromosome rearrangement in myeloid neoplasia. Interestingly, the plasminogen activator inhibitor type I, multi-drug resistance, and erythropoietin genes are located at band 7q22 and the insulin receptor gene is located at band 19p13.3. Both sites contain fragile site loci. The possible role of these fragile sites, genes, or other genes in the rearrangement can only be surmised. PMID- 1756495 TI - del(2)(p23): a consistent recurrent abnormality in acute myelogenous leukemia. AB - A case of acute myelogenous leukemia (AML-M2) with an unusual chromosomal finding is presented. In addition to the most frequently observed translocation in this neoplasia, involving the long arms of chromosomes 8 and 21, there was a partial deletion of the short arm of chromosome 2 band (p23), i.e., 46,XX,del(2)(p23),t(8;21)(q22;q22). Deletion of the short arm of chromosome 2 has been described in association with other chromosome abnormalities in two other cases of AML and as the sole abnormality in three cases of AML, indicating that this abnormality is nonrandom and may be associated with leukemic transformation of hematopoietic cells. Therefore, we propose that the del(2)(p23),t(8;21)(q22;q22) abnormality be accorded status III and possibly considered a subset of AML (M2). PMID- 1756496 TI - Molecular cytogenetic analysis of a medulloblastoma with isochromosome 17 and double minutes. AB - Cytogenetic analysis of a medulloblastoma revealed two abnormal cell lines of 48,XY, +8, +8, -14, +der(14)t(1;14)(q11;p11),i(17q) and 51,XY, +5, +6, +8, +8, 14 + 20, +der (14)t(1;14)(q11;p11),i(17q), + dmin. The finding of double minute chromosomes in some medulloblastomas has been associated with amplification of the c-myc or N-myc oncogenes. We were unable to detect gene amplification with these probes by Southern blot analysis. PMID- 1756497 TI - Complex karyotypic evolution in B-cell chronic lymphocytic leukemia. AB - Cytogenetic analysis at diagnosis in a female patient with chronic B-cell leukemia showed a single abnormal clone with a 4p+ abnormality, 46,XX, -4, +der(4)t(4;?)(p16;?). Six additional clones evolved from this clone during the following 4 1/2 years and showed 3p+, 4p-, and 11q- chromosomes in addition to the 4p+ abnormality. Immunoglobulin heavy chain gene rearrangement studies showed two rearranged bands and a faint germline band. Following splenectomy, a strong germline and faint rearranged bands were seen, suggesting that the majority of cells were normal, whereas cytogenetic studies showed that the karyotypically abnormal cells were still present. The combination of cytogenetic and Ig gene rearrangement studies provides detailed information regarding the number of circulating normal and leukemic cells. PMID- 1756498 TI - Chromosomal abnormalities in childhood acute nonlymphocytic leukemia (M4). AB - A new reciprocal, apparently balanced translocation between chromosomes 7 and 22, i.e., t(7;22)(p22;q13), in association with inv(16)(p13q22) in a child with acute nonlymphocytic leukemia (M4) is reported. Five percent of her bone marrow cells contained both of these aberrations while 90% of her cells have the pericentric inversion of chromosome 16 as the sole abnormality. A clonal evolution of the unusual cell line may be associated with atypical clinical presentation. The presence of inversion 16 in adults has a better prognosis as compared with children. A concise review on the cytogenetic findings in children with ANLL(M4) is also provided. PMID- 1756499 TI - Report of a variant t(1;15;17)(p36;q22;q21.1) in a patient with acute promyelocytic leukemia. AB - Chromosome analysis of bone marrow aspirate from a 46-year-old man with acute promyelocytic leukemia (APL) revealed a variant translocation, 46,XY,t(1:15;17)(p36;q22;q21.1). The breakpoints in chromosomes 15 and 17 appear to be the same as those in the more common translocation, t(15;17), associated with APL. The common translocation has been reported in up to 80% of cases of APL. Seventeen cases with variant translocations have been reported involving 15 alone, 17 alone, or 15, 17, and some other chromosome. PMID- 1756500 TI - Cytogenetic study of a papillary thyroid carcinoma with a rearranged chromosome 10. AB - Cytogenetic findings of a multifocal papillary thyroid cancer and a metastatic lymph node from a 29-year-old white female patient are reported. Two clonal aberrations were observed: a trisomy 7 in one nodule, and a rearranged chromosome 10 in a separate nodule and in a lymph node. The rearrangement of 10q described here is similar to other published cases and is relevant for interpreting the molecular findings associated with thyroid cancer. PMID- 1756501 TI - A 46,XY female with mixed gonadal dysgenesis and a 48,XY, +7, +i(12p) chromosome pattern in a primary gonadal tumor. AB - Cytogenetic analysis of a primary germ-cell tumor originating from the streak gonad of a 20-year-old phenotypic female with a 46,XY karyotype and mixed gonadal dysgenesis revealed a 48,XY, +7, +i(12p) chromosomal pattern. Germ-cell tumors originating from gonads of normal males are usually highly aneuploid. An isochromosome 12p as well as an overrepresentation of chromosome 7 material are among the specific changes most consistently observed. The present case shows that tumors of dysgenetic gonads, albeit being near-diploid, may exhibit similar chromosomal changes. This observation lends additional support to the hypothesis that these specific cytogenetic anomalies may play an important role in the pathogenesis of human germ-cell tumors. PMID- 1756502 TI - Inversion 16 and translocation (16;16) in ANLL M4eo break in the same subregion of the short arm of chromosome 16. PMID- 1756503 TI - Total loss of chromosome 17 and p53 gene in solid cancers. PMID- 1756504 TI - Homozygote breakpoint in 13q14 in a case of chronic lymphocytic leukemia. PMID- 1756505 TI - t(3;5)(q25;q33) in myelodysplastic syndrome. PMID- 1756506 TI - A new case of medulloblastoma in an adult. PMID- 1756507 TI - The inhibition of platelet aggregation of metastatic H-ras-transformed 10T1/2 fibroblasts with castanospermine, an N-linked glycoprotein processing inhibitor. AB - A series of T24-H-ras-transformed 10T1/2 fibroblasts with varying metastatic potential was tested for the ability to aggregate platelets. Results indicate that although platelet activation was always detected in the highly metastatic cells, some non-metastatic cells also have the ability to cause platelet aggregation, suggesting that this is a necessary but not sufficient characteristic of the metastatic phenotype. Apyrase, an ADP scavenger, effectively inhibited platelet aggregation by metastatic cells, however, there was no significant increase in ADP secretion or relation to the ability of the tumor cells to activate platelets. Hirudin, a thrombin inhibitor, did not affect aggregation, suggesting that the pathway of activation is thrombin-independent. The glycoprotein processing inhibitor, castanospermine, which reduces glycosidase I activity and metastatic capability, inhibited the ability of metastatic cells to cause platelet aggregation. However, another inhibitor of oligosaccharide processing, swainsonine, which inhibits mannosidase II activity and does not reduce metastasis, had no effect on platelet aggregation. These results show that the integrity of N-linked oligosaccharide structure of glycoproteins is an important feature of the ability of ras-transformed fibroblasts to activate platelets. PMID- 1756508 TI - Diffuse and continuous cell proliferation enhances radiation-induced tumorigenesis in hamster lung. AB - Syrian Golden hamsters received 8 weekly intratracheal instillations of 0.2 microCi of the alpha-emitting isotope Po210 while being exposed to an atmosphere of 65% oxygen in the inspired air. Three months later, 42% of the animals had poorly differentiated lung carcinomas. On the other hand, no lung tumors were found in hamsters that received intratracheal instillations of Po210 and were kept in air. It is concluded that diffuse cell hyperplasia in the lung, caused by an inhalant, may constitute an additional risk factor in the pathogenesis of alpha-radiation induced lung cancer. PMID- 1756509 TI - Comparative studies on genotoxic and carcinogenic effects of different cytostatic protocols. I. In vivo cytogenetic analyses in CBA mice. AB - In vivo rodent cytogenetics may provide an important basis for an animal model for the assessment of the carcinogenic potential of antitumor drugs in man. In this paper, genotoxic alterations (i.e. sister chromatid exchanges and micronuclei) caused by different cytostatic protocols in CBA/Ca mice are described. The strongest sister chromatid exchange inducing effects were shown by the ABVD (doxorubicin-dacarbazine-bleomycinvinblastine) group and combinations containing cyclophosphamide. Compounds which affect the mitotic spindle induced only micronuclei, but not sister chromatid exchanges. PMID- 1756510 TI - Effects of the synthetic trypsin inhibitor camostate on the development of N nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters. AB - Trypsin inhibitors have been shown to promote pancreatic growth as well as the development of pancreatic tumours in rats. The present study was carried out to examine the effects of the synthetic trypsin inhibitor camostate on the growth of the pancreas and on the development of pancreatic preneoplastic and neoplastic lesions in hamsters treated with N-nitrosobis(2-oxopropyl)amine. A specific cholecystokinin-receptor antagonist was administered to determine the role of cholecystokinin in camostate action. The animals were killed 19 weeks after the first injection with N-nitrosobis(2-oxopropyl)amine. Camostate caused an increase in growth of the pancreas and a decrease in the number of (pre)neoplastic ductular pancreatic lesions. Lorglumide (CR-1409) did not influence these effects of camostate. It was concluded that rats and hamsters behave differently with regard to the effect of camostate on pancreatic growth and carcinogenesis. PMID- 1756511 TI - Double screening of suramin derivatives on human colon cancer cells and on neural cells provides new therapeutic agents with reduced toxicity. AB - Suramin is a polyanionic compound currently used under evaluation for antineoplastic activity. One of the main problems encountered during clinical trials was an adverse neurotoxic effect, probably due to a direct cytotoxic effect on neural cells. Suramin is also known to trigger differentiation of human colon cancer cells, yet a chronic treatment induces a lysosomal storage disorder. The aim of this study was to evaluate suramin analogs for their effect: (i) on the lysosomal system of the human colon cancer cell clone HT29-D4; and (ii) on C6 glioma cell growth and morphology. One of the derivatives tested, NF036, induced terminal differentiation of HT29-D4 cells without any impairment of the lysosomal system. Furthermore, in contrast to suramin, NF036 did not alter C6 cell growth and morphology. We conclude that there is a relationship between the ability of a suramin derivative to induce a lysosomal storage disorder in human colon cancer cells and its neurotoxic effect. A double screening of suramin analogs on HT29-D4 and C6 cells allowed us to identify a new candidate antineoplastic drug: NF036. PMID- 1756512 TI - Modulation of the reversibility of actinomycin D cytotoxicity in HeLa cells by verapamil. AB - Actinomycin D treatment (0.001-0.005 micrograms/ml; 0.5-24 h) induced a dose and time response shifting of nucleolar to nuclear fluorescence. In the presence of verapamil, cells were more responsive to actinomycin D. Translocation of protein B23 occurred with lower doses of actinomycin D and in shorter incubation times in the presence of verapamil. Short exposure (0.5 h) of HeLa cells to actinomycin D (0.05-0.25 micrograms/ml) induced 'reversible' translocation of protein B23 as well as 'reversible' inhibition of cell growth and RNA synthesis. Verapamil (5 microM) included in the cell culture after removal of actinomycin D inhibited the recoveries of cell growth, RNA synthesis as well as the corresponding relocalization of protein B23 from the nucleoplasm to nucleoli. These results indicate that verapamil can potentiate the antiproliferating activity of actinomycin D by inhibiting reversibility of its cytotoxicity and suggest clinical application. PMID- 1756513 TI - Visualization of a protein involved in seric immune complexes of patients with epithelial tumors having elevated levels of anti-'benzo[a]pyrene-like' IgA. AB - Many authors have previously described that several types of human cancer were associated with elevated levels of IgA and IgA-containing immune complexes. We have recently identified and characterized IgA directed against a "benzo[a]pyrene like' antigen in sera of patients with mammary tumors. Circulating immune complexes from these sera were precipitated and analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 18-20-kDa protein was found closely associated with high levels of anti-'benzo[a]pyrene-like' IgA in sera of patients having a proliferative pathology. PMID- 1756514 TI - On the long-term toxic risk of dinaline. AB - The long-term toxic risk of the cytostatic agent dinaline (4-amino-N-(2' aminophenyl)-benzamide) was assessed in a rat bioassay. Regular administration of 9, 3 and 1 mg/kg for 106 weeks was associated with significantly increased survival of female rats receiving the median and low doses. Dinaline significantly reduced the occurrence of malignant tumors in male rats and prolonged the manifestation time of malignancies in female rats. Unlike malignant tumors, benign neoplasms were increased in male rats and were not significantly different from controls in female rats. Analysis of organ distribution of neoplastic lesions revealed a dose-dependently decreased tumor incidence in the hematopoietic and lymphatic tissue, the mammary gland (females only) and the pituitary gland and a not dose dependently reduced incidence of liver tumors. This contrasted with dose dependently increased tumor incidences in the adrenal gland, the gonads and the vagina. Considering these findings, dinaline has to be assessed as a modulator of carcinogenesis in rats. The observed decreased and increased tumor incidences suggest a hormone-related mechanism of action. PMID- 1756515 TI - Levels of the adducts of 4-aminobiphenyl to hemoglobin in control subjects and bladder carcinoma patients. AB - We determined the hemoglobin adduct levels of one aromatic amine of cigarette smoke, 4-aminobiphenyl (4-ABP), in smoking controls and in patients with transitional cell bladder carcinoma. Covalently bound 4-ABP was measured by capillary gas-chromatography and negative-ion chemical ionization mass spectrometry, using deuterated 4-ABP as internal standard. Smoking was quantified measuring the urinary excretion of cotinine. Thirteen cases and controls were paired for urinary cotinine levels. Bladder carcinoma patients had slightly higher levels of 4-ABP hemoglobin adducts than controls (means +/- S.D. were 103 +/- 47 and 65 +/- 44, respectively). This difference was significant using a t test for paired samples (P = 0.04) and non-parametric Kruskal-Wallis rank analysis (P = 0.033). PMID- 1756516 TI - Inhibitory effects of Ixora javanica extract on skin chemical carcinogenesis in mice and its antitumour activity. AB - Topical application of 100 mg/kg body weight of Ixora javanica flower extract inhibited the growth and delayed the onset of papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil. The extract at the same dose, when administered orally inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA)-induced soft tissue fibrosarcomas significantly. Oral administration of 200 mg/kg of the extract inhibited the growth of intraperitoneally transplanted sarcoma-180 and Ehrlich ascites carcinoma tumours besides showing an increase in the life span of the treated mice. Toxicity studies showed that the blood urea nitrogen levels were elevated post treatment. The active compounds responsible for the above inhibitory effects on tumour growth were identified as ferulic acid (4-hydroxy-3 methoxy cinnamic acid) and its regionmer 3-hydroxy-4-methoxy cinnamic acid. PMID- 1756517 TI - Effects of antioxidants on quercetin-induced nuclear DNA damage and lipid peroxidation. AB - The effects of catalase, superoxide dismutase, mannitol, glutathione, and diallyl sulfide on quercetin-induced DNA damage and lipid peroxidation were investigated in a model system of isolated rat-liver nuclei under aerobic conditions and in the presence of equimolar iron or copper. Mannitol produced a small but significant inhibition of the concurrent nuclear DNA damage and lipid peroxidation induced by quercetin in the presence of iron or copper. Catalase significantly decreased quercetin-induced nuclear DNA damage only in the presence of iron and had no significant effect on lipid peroxidation. Superoxide dismutase showed no significant effect on nuclear DNA damage, but stimulated the quercetin induced lipid peroxidation only in the presence of copper. Glutathione significantly inhibited the nuclear lipid peroxidation but enhanced the DNA damage. Diallyl sulfide significantly enhanced the nuclear DNA damage but stimulated the lipid peroxidation only in the presence of iron. These results suggest that the reactive oxygen species, especially the hydroxyl radicals, are responsible for the concurrent lipid peroxidation and DNA damage induced by quercetin in the presence of iron or copper in isolated rat-liver nuclei. PMID- 1756518 TI - Staphylococcus saprophyticus urinary-tract infection in male children. AB - Staphylococcus saprophyticus urinary-tract infection has been reported to occur in sexually active young females and in geriatric patients with obstructive uropathy. We are discussing two young male children with S. saprophyticus urinary tract infection. We draw attention to this bacterium which is emerging as an important pathogen in children with urinary-tract infections. PMID- 1756519 TI - Severe hyperlipidemia due to multiple factors in a child with nephrotic syndrome. AB - An unusual case of severe hypercholesterolemia and hypertriglyceridemia is described in a child with nephrotic syndrome. The severe hyperlipidemia in this patient was most likely induced by multiple interacting factors which included the metabolic abnormalities of nephrotic syndrome, steroid therapy, the underlying genetic predisposition of ApoE-2 homozygosity as well as diet and diuretic therapy. The result of these factors was an extremely severe type III hyperlipoproteinemia. The pathogenesis of hyperlipidemia in this setting is discussed. PMID- 1756520 TI - Transient renal insufficiency in the neonate related to hyperuricemia and hyperuricosuria. AB - Transient renal insufficiency in the neonate is frequently the result of hypoperfusion of the kidneys due to circulatory compromise and is associated with a normal renal ultrasound scan. We describe an infant with transient renal insufficiency associated with hyperuricemia, hyperuricosuria and increased echogenicity of the renal medullary pyramids. Transient uric acid nephropathy may be a more common occurrence in the neonate than previously recognized. PMID- 1756521 TI - Adaptation of renal sulfate transport in response to dietary sulfate intake in guinea pigs. AB - Inorganic sulfate reabsorption was studied during sulfate infusion in guinea pigs stabilized on high-sulfate, normal-sulfate or low-sulfate diets. Guinea pigs stabilized on a low-sulfate diet exhibited 86-91% fractional sulfate reabsorption at normal plasma sulfate concentrations. Fractional renal sulfate reabsorption in animals stabilized on a high-sulfate diet was 55-70%. Clearance techniques were used to determine the glomerular filtration rate and the fractional reabsorption of sulfate during sulfate infusion. Animals fed a high-sulfate diet manifested marked sulfaturia in response to sulfate infusion. The increase in fractional reabsorption associated with decreases in dietary sulfate intake suggests a tubular adaptive mechanism, similar to that demonstrated for phosphate, to increase sulfate reabsorption and maintain constant plasma sulfate concentration. Dietary sulfate-dependent alterations in renal sulfate reabsorption may play a significant role in establishing the rate of sulfate excretion and thus regulating sulfate balance. PMID- 1756522 TI - Water-salt metabolism of feti and pregnant rats with venous congestion. AB - Water and salt metabolism was studied in feti and pregnant rats with experimental venous congestion by measuring water and electrolyte content in the kidney, liver, cerebrum, skin hypodermic tissue, muscle, heart. In the kidney, venous occlusion resulted in increased potassium content. The role of the placenta is discussed. PMID- 1756523 TI - Role of 1,25-dihydroxyvitamin D production in idiopathic hypercalciuria. AB - In 9 children with idiopathic hypercalciuria, an oral calcium-loading test was performed. After this calcium excretion, vitamin D levels, parathyroid hormone levels and phosphate excretion were measured during a period of calcium restriction, a period of high calcium intake and a period of low calcium intake and phosphate supplementation. In our patients, there was no correlation between calcium excretion following acute and long-term calcium loading. Phosphate excretion was normal during the periods of low and high calcium intake and there were no signs of renal phosphate leakage. Elevated levels of 1,25 dihydroxyvitamin D were found with no significant change after altering phosphate or calcium intake (95% confidence intervals for the difference in 1,25 dihydroxyvitamin D levels were -2.2-15.4 pg/ml in the period with low and high calcium intake; -19.8-28.2 pg/ml in the period with low calcium intake and extra phosphate, and -24.2-19.6 pg/ml in the period with high calcium intake and extra phosphate). These data support the hypothesis of an autonomously elevated 1,25 dihydroxyvitamin D level as pathogenetic mechanism for idiopathic hypercalciuria. PMID- 1756524 TI - Nitrogen and amino acid balance during total parenteral nutrition and continuous arteriovenous hemofiltration in critically ill anuric children. AB - Amino acid balance and nitrogen balance during total parenteral nutrition (TPN) and continuous arteriovenous hemofiltration (CAVH) were investigated in 11 critically ill anuric patients during the first 7 days after onset of anuria. Nitrogen intake ranged from 0.115 +/- 0.013 (SEM) g/kg/day on day 1 to 0.291 +/- 0.029 (SEM) g/kg/day on day 7. After 7 days of TPN, 9 patients had a positive cumulative protein-N balance of 287.52 +/- 68.52 (SEM) mg/kg, 2 patients had a negative balance of 781.8 and 1,103.2 mg/kg, respectively. Mean amino acid loss in ultrafiltrate was 0.159 +/- 0.008 (SEM) g/kg/day. Four patients died without recovery of renal function. PMID- 1756525 TI - Urinary catecholamine in children with diabetic ketoacidosis. AB - Urinary excretion of norepinephrine, epinephrine and dopamine was investigated in children with diabetic ketoacidosis. Besides pronounced hyperglycemia and metabolic acidosis, severe hypovolemia was also observed. At the onset of the study, urinary excretion of norepinephrine, epinephrine and dopamine was markedly elevated. Fluid replacement decreased urinary catecholamine excretion. Norepinephrine: 996 +/- 97 vs. 253 +/- 29; dopamine: 5,108 +/- 480 vs. 3,175 +/- 715; epinephrine: 402 +/- 81 vs. 77 +/- 200 pmol/min/1.73 m2. During ketoacidosis, there was a significant negative correlation between urinary norepinephrine excretion and endogenous creatinine clearance. Urinary output of both norepinephrine and dopamine correlated significantly with diuresis, while sodium excretion only correlated with dopamine excretion. Our data suggest that in diabetic ketoacidosis increased urinary excretion of norepinephrine may participate in renal hypoperfusion and hypofiltration. Elevated renal dopamine production contributes to sodium loss, characteristic for diabetic ketoacidosis. PMID- 1756526 TI - Congenital urinary abnormalities and neural tube defects. AB - The records of 178 children with a neural tube defect were reviewed to determine the pattern of associated congenital urinary malformation. Ten (6%) of the children had a significant congenital urinary malformation. Although unilateral renal agenesis was the most common single congenital urinary abnormality, as a group, abnormalities in fusion or migration were equally common in this study and more common in several previously reported studies. Lower congenital urinary tract abnormalities were also identified but were less common. No correlation was found between the level of the neural tube defect and the specific congenital urinary abnormality. PMID- 1756527 TI - Renal function in preterm twins with birthweight discordance. AB - To evaluate the development of renal function in fetal malnutrition conditions, we tested glomerular filtration rate and fractional sodium excretion (FENa) of premature twins at birth (less than or equal to 35 weeks gestational age) with birthweight discordance, divided according to birthweight (less than or equal to 10% group A; higher birthweight group B). Groups A and B of twins are comparable in fluid intake, biochemical serum tests (glucose, sodium, potassium, albumin, total protein, osmolality and hematocrit) and also in percent weight decrease at 24 h of life. Moreover, both creatinine clearance (CrCl) and FENa result respectively correlated directly (r = +0.63) and indirectly (r = -0.46) with gestational age of twins. Consequently, CrCl (8.3 +/- 4.3 vs 8.3 +/- 4.5 ml/min/1.73 m2) and FENa (3 +/- 2.8 vs. 2.7 +/- 2.8%) do not result different in relation to birthweight discordance of premature twins. In conclusion, at birth, gestational age is the main determinant of kidney function in premature twins with birthweight discordance. PMID- 1756528 TI - Progression of chronic renal failure. AB - The deterioration rate of creatinine clearance (CCr) was studied in 40 children with chronic renal failure (CRF) on conservative treatment followed up for at least 1 year (range 1-12). The deterioration rate of CCr was significantly (p less than 0.01) higher in glomerulopathies (G) than in hypoplasias (H) and in vascular nephropathies (VN) and significantly (p less than 0.01) higher in hereditary nephropathies (HN) than in VN. The differences in the deterioration rate of CCr between H and HN and between H and VN were not explainable on the basis of the different age at diagnosis or of the different prevalence of hypertension. These data indicate that the primary renal disease is important in determining the progression of CRF. PMID- 1756529 TI - Imaging of urinary tract malformations: intravenous urography and/or kidney ultrasonography? AB - We performed both kidney ultrasonography (KUS) and intravenous urography (IVU) in 56 children with urinary tract infections (UTI) to compare the effectiveness of these procedures in detecting urinary tract malformations (UTMs). In 7 patients where KUS findings were interpreted as normal, IVU detected the following UTMs: hydronephrosis (3), stenosis of the pelvi-ureteric junction (2), pelvi-ureteric duplication (1) and kidney dislocation (1). In 2 other patients, mild hydronephrosis diagnosed by KUS was not confirmed by IVU. With respect to IVU, KUS revealed a sensitivity of 77.4% and a specificity of 92%. In our experience, IVU is still irreplaceable in the diagnostic protocol of UTMs in children; KUS should be regarded as a useful complementary procedure. PMID- 1756530 TI - Cyclophosphamide modifies the induction kinetics but not cell types and cytotoxic mechanisms of antitumor cells elicited with OK-432 plus attenuated tumor cells. AB - The present study was designed to examine whether the antitumor cells induced by treatment with mitomycin-C-treated EL4 cells (EL4MMC) plus OK-432 plus cyclophosphamide differed from those induced by treatment with EL4MMC plus OK-432 in terms of their cell types and antitumor mechanisms. Antitumor activity of peritoneal exudate cells (PEC) from mice receiving either treatment was nonspecific, and inhibition of their target cell growth increased for up to 24 h. Macrophage toxin, silica and trypan blue abrogated the activity in vitro and in vivo, respectively. The activity of the PEC was inhibited with inhibitors of the arachidonic acid cascade, such as dexamethasone, 4-bromophenacyl bromide and nordihydroguaiaretic acid but not esculetin, ibuprofen, indomethacin and BW755C. NG-monomethyl-L-arginine, a specific competitive inhibitor of the L-arginine dependent nitric oxide synthesis, also inhibited the activity. These results and morphological observations indicated that antitumor cells in the PEC from mice receiving either treatment were macrophages, and that their activity was closely related to the arachidonic acid cascade and to nitric oxide. Antitumor activity of the PEC spontaneously decayed in vitro and this decay was inhibited by the addition of OK-432 or lipopolysaccharide. On the other hand, cyclophosphamide sustained the appearance of antitumor cells in mice treated with EL4MMC plus OK 432. Therefore, cyclophosphamide treatment did not modify cell types and cytotoxic mechanisms of antitumor cells elicited with EL4MMC plus OK-432, but did modify the induction kinetics of such antitumor macrophages. PMID- 1756531 TI - Endogenous interferon alpha/beta produced by Kupffer cells inhibits interleukin 1, tumor necrosis factor alpha production and interleukin-2-induced activation of nonparenchymal liver cells. AB - We have previously reported liver-specific interferon (IFN) alpha/beta production by murine Kupffer cells that was not observed with other tissue macrophages incubated in the absence of stimulators such as IFN gamma or lipopolysaccharide (LPS). Consequently, while interleukin-2 (IL-2) alone induced pronounced lymphokine-activated killer (LAK) activity from splenocytes, combination of anti IFN alpha/beta antibody with IL-2 was required to generate significant LAK activity from nonparenchymal liver cells. This endogenous IFN alpha/beta production by Kupffer cells was not induced by LPS because (a) addition of polymyxin B did not abolish the positive effects of anti-IFN alpha/beta antibody on nonparenchymal liver cells, and (b) similar results were obtained when comparing the responses of LPS-responsive C3HeB/FeJ and LPS-hyporesponsive C3H/HeJ mice. The possibility of hepatotropic infection was also ruled out in that anti-IFN alpha/beta antibody enhanced hepatic but not splenic LAK cell induction in vitro in both conventional and germ-free C3H/HeN mice. IFN alpha/beta played an autoregulatory role by down-regulating the production of IL 1 and tumor necrosis factor alpha by Kupffer cells. However, the augmenting effect of anti-IFN alpha/beta antibody on LAK induction from non-parenchymal liver cells was not mediated through an increase in the level of either IL-1 or TNF alpha, as specific antisera against either cytokine did not abrogate this positive effect. Finally, flow-cytometry analysis showed that IFN alpha/beta significantly diminished the expression of IL-2 receptor alpha chain, indicating an inhibition of LAK cell generation at a relatively early stage of induction. PMID- 1756532 TI - Generation of T cell clones binding F(ab')2 fragments of the idiotypic immunoglobulin in patients with monoclonal gammopathy. AB - Lymphocytes from two patients with multiple myeloma stage I and one patient with monoclonal gammopathy of undetermined significance were found to proliferate specifically in response to low concentrations of F(ab')2 fragments of the autologous M component. T cell clones isolated from repeatedly stimulated cultures bound specifically the autologous idiotype and proliferated after addition of soluble idiotype and exogenous interleukin-2. The majority of clones were CD8+ and showed negligible staining for CD4. Idiotype-binding clones could not be isolated from cultures of lymphocytes from a healthy control stimulated under the same conditions. The study provides support for the existence of idiotype-reactive T cells in monoclonal gammopathies. Such cells might have a regulatory role on the tumor cell clone and may be important for a future therapeutic approach. PMID- 1756533 TI - Immunity to melanoma in mice immunized with transfected allogeneic mouse fibroblasts expressing melanoma-associated antigens. AB - Transfection of genomic DNA from B16 mouse melanoma into LM(TK-) fibroblasts led to the generation of several clones of transfected cells that strongly expressed B16 melanoma-associated antigens (MAA). The transfected cells retained their H-2k markers and served as allogenic cells with expressive MAA in C57BL/6 mice, syngeneic with the melanoma. The cells were capable of eliciting primary anti-B16 immune responses in vitro in spleen cells from C57BL/6 mice. Immunization of C57BL/6 mice with the transfected cells led to the generation of anti-B16 cytotoxic activity in spleen cells, and C57BL/6 mice immunized with the MAA positive transfected cells were partially resistant to a lethal challenge with B16 melanoma cells. Under similar conditions, B16 cells were nonimmunogenic. Therefore, transfected allogeneic LM(TK-) fibroblast cells expressing MAA served as more potent anti-melanoma immunogens than the parental B16 tumor cells themselves. PMID- 1756534 TI - Pharmacokinetics and biological activity in subcutaneous long-term administration of recombinant interferon-gamma in cancer patients. AB - We have investigated the pharmacokinetics, tolerance, and biological activity of recombinant human interferon-gamma (rHuIFN gamma) administered subcutaneously to cancer patients. Twenty-one patients with lymphoma and metastatic cancer received rHuIFN gamma (in doses of 0.1, 0.25, or 0.5 mg/m2) in two or three injections per week for up to 180 days. The most common adverse effects encountered were flu like symptoms, fever and fatigue. The increase in body temperature after each administration ranged from 0 to 4 degrees C depending on the individual patient, but was unrelated to the rHuIFN gamma dose or its plasma concentration. The pharmacokinetic response of the patients after the two treatments showed a low intra-individual variability with respect to the plasma concentration/time profiles. However, as observed for the fever side-effect, the interindividual variation (CV greater than 50%) was high for the parameters area under the data points (AUC0-t) and maximum plasma concentration (cmax). Despite this high interindividual variability, the mean values obtained for AUC0-t and cmax after s.c. injection of rHuIFN gamma were approximately proportional to the dose administered: the injection of 0.1, 0.25 or 0.5 mg/m2 rHuIFN gamma resulted in AUC0-t values of 15.4, 31.5 or 69.6 ng h/ml, respectively and cmax was found to be 1.0, 2.4 and 4.9 ng/ml, respectively. With this s.c. administration protocol, objective antitumour responses were observed in two patients, but there was no partial or complete remission. PMID- 1756535 TI - Immunotherapy of bovine ocular squamous cell carcinoma by repeated intralesional injections of live bacillus Calmette-Guerin (BCG) or BCG cell walls. AB - Thirty cows of the Dutch Friesian and the Maas-Rijn-Ijssel breed with histologically confirmed ocular squamous cell carcinoma were treated by repeated intralesional injection of live bacillus Calmette-Guerin (BCG) (n = 14) or a BCG cell-wall vaccine (n = 16). Complete regression of the primary tumour was observed in 64% and 57% of the animals respectively. In the 2-year follow-up period there was no recurrence of primary tumours. This sharply contrasts with the recurrence frequency (40%-50%) after complete remission induced by a single intralesional injection with BCG, observed in an earlier study. In 1 animal a new primary tumour developed. At necropsy metastases were present in 33% of the treated animals: in 3 of 17 animals that showed complete regression of the primary tumour and in 7 of 13 animals with partial regression or progressive disease. This did not differ significantly from results obtained after a single treatment (27%). Delayed-type hypersensitivity to M. bovis purified protein derivative (PPD) was more persistent in animals showing regression of the primary tumour than in non-responding animals. Of the animals with a positive PPD response 6 months after treatment, 79% showed tumour regression. Regression was observed in only 28% of the animals not responding to PPD after the same period of time. IN CONCLUSION: (a) recurrence of the primary tumour was not observed after repeated BCG treatment; (b) the frequency of metastases was not decreased compared to results obtained with a single treatment; (c) regression was correlated with a positive delayed-type hypersensitivity reaction to PPD (P less than 0.05) 6 months after treatment; (d) no significant differences were observed when the clinical results of treatment with live BCG and the BCG cell wall vaccine were compared. PMID- 1756536 TI - Pharmacokinetics and biodistribution of a new anti-episialin monoclonal antibody 139H2 in ovarian-cancer-bearing nude mice. AB - The new murine anti-episialin monoclonal antibody (mAb) 139H2 has been selected for its strong reactivity with a series of human ovarian cancer xenografts. In the present report we describe the characteristics of mAb 139H2 investigated in vitro as well as in vivo. Scatchard plot analysis using the human ovarian cancer cell line NIH:OVCAR-3 showed an affinity constant of 1 x 10(8) M-1 and the expression of 7 x 10(6) antigenic sites/cell. Reactivity with OVCAR-3 xenograft tissue was intense, localized at the cell membrane, heterogeneously distributed, and mainly detectable at the apical site of the cell. Administration of radiolabelled mAb 139H2 to nude mice bearing s.c. OVCAR-3 xenografts showed specific uptake in the tumour up to 9% of the injected dose/g. The maximum uptake in the tumour was retained for 3.5 days and mAb 139H2 cleared from the tumour with a half-life of 5.5 days. The half-life in blood was 50 h and no antibody antigen complex formation could be detected. Poor uptake and no retention in episialin-negative WiDr colon cancer xenografts demonstrated specificity. Administration of an excess of an unlabelled irrelevant mAb did not influence the uptake in the OVCAR-3 xenografts or in other tissues. In contrast, tumour uptake decreased after addition of 300 micrograms or more unlabelled mAb 139H2 to a tracer dose of radiolabelled mAb 139H2. The uptake of mAb 139H2 in OVCAR-3 xenografts appeared inversely related to the tumour size. PMID- 1756537 TI - A potent and specific immunotoxin for tumor cells expressing disialoganglioside GD2. AB - Monoclonal antibody 14G2a (anti-GD2) reacts with cell lines and tumor tissues of neuroectodermal origin that express disialoganglioside GD2. mAb 14G2a was coupled to the ribosome-inactivating plant toxin gelonin with the heterobifunctional cross-linking reagent N-succinimidyl-3(2-pyridyldithio)propionate. The activity of the immunotoxin was assessed by a cell-free translation assay that confirmed the presence of active gelonin coupled to 14G2a. Data from an enzyme-linked immunosorbent assay demonstrated the specificity and immunoreactivity of the 14G2a-gelonin immunotoxin, which was identical to that of native 14G2a. Assays for complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) revealed that these functional properties of the native 14G2a antibody were also preserved in the 14G2a-gelonin immunotoxin. The gelonin-14G2a immunotoxin was directly cytotoxic to human melanoma (A375-M and AAB-527) cells and was 1000-fold more active than native gelonin in inhibiting the growth of human melanoma cells in vitro. The augmentation of tumor cell killing of 14G2a gelonin immunotoxin was examined with several lysosomotropic compounds. Chloroquine and monensin, when combined with 14G2a-gelonin immunotoxin, augmented its cytotoxicity more than 10-fold. Biological response modifiers such as tumor necrosis factor alpha and interferon alpha and chemotherapeutic agents such as cisplatinum and N,N'-bis(2-chloroethyl)-N-nitrosourea (carmustine) augmented the cytotoxicity of 14G2a-gelonin 4- to 5-fold. The results of these studies suggest that 14G2a-gelonin may operate directly by both cytotoxic efforts and indirectly by mediating both ADCC and CDC activity against tumor cells; thus it may prove useful in the future for therapy of human neuroectodermal tumors. PMID- 1756539 TI - Isolated atrial myocardial infarction: pathological and clinical features in 10 cases. AB - Isolated myocardial infarction of the atria is a relatively understudied and underestimated entity, rarely diagnosed in life. The pathological and clinical features in 10 cases of acute isolated atrial myocardial infarction are reported. They represent 3.5% of all myocardial necrosis out of a series of 2,704 consecutive autopsies in adults. The right atrium is more frequently involved than the left atrium (9:1). Pulmonary hypertension, with or without coronary arterial narrowing, is the major condition leading to isolated atrial infarction. Congestive heart failure, thromboembolic phenomena, and supraventricular arrhythmias are the most frequent complications of atrial infarction. The electrocardiographic findings are often non-specific and elusive and are not useful to a correct diagnosis. These observations suggest that isolated atrial myocardial infarction is a well-distinct entity with respect to ventricular myocardial infarction, since there are several differences between the 2 diseases in pathogenesis, diagnosis, clinical picture, and prognosis. PMID- 1756538 TI - Impairment in proliferation, lymphokine production and frequency distribution of mitogen-responsive and interleukin-2-producing cells in Hodgkin's disease. AB - In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon gamma (IFN gamma), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFN gamma in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFN gamma. Levels of IL-2 and IFN gamma in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regression (r = 0.79 and r = 0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate (r = +0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111-1/554 and 1/3009-1/6709 respectively) were also less than those of the healthy donors (ranges 1/80-1/181 and 1/761-1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11,214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2 producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease. PMID- 1756540 TI - [The usefulness of the echo-dipyridamole and exercise tests in risk stratification in patients with acute uncomplicated myocardial infarct after systemic thrombolysis]. AB - We studied 142 patients (121 males, 21 females) survivors of a first non complicated acute myocardial infarction (AMI) treated with thrombolytic therapy between March 1988 and December 1989. Dipyridamole echocardiography test (DET, 67 patients) and exercise electrocardiography test (EET, 104 patients) were performed to assess sensitivity and specificity in identifying patients at risk for an unfavorable clinical outcome and subsequent cardiac events: 67 patients underwent coronary arteriography within 4 weeks after AMI. DET positivity was related to the detection of a new transient asynergy of contraction either in infarct area or in remote zones. The mean follow-up period was 12 months (range 4 20). Clinical follow-up end-points of the study included death, re-AMI, angina. Sensitivity and specificity of EET and DET were 75 and 68%, 53 and 71% respectively. If EET plus DET were considered, sensitivity was 81% and specificity 60%. The fairly good DET sensitivity and specificity could be partially explained by some stunned myocardium exhibiting prolonged contractile dysfunction despite myocardial reperfusion. EET sensitivity and specificity is comparable to previous observations in AMI not treated with thrombolytic therapy. DET seems to be a useful and safe test in prognostic evaluation of asymptomatic patients after thrombolysed AMI, but its value is improved in association with EET. PMID- 1756541 TI - [Hemodynamic and clinical effects and treatment tolerance with low-dose iv amrinone in patients with refractory heart failure: a multicenter study. The Group for Research on Amrinone in the Treatment of Refractory Heart Failure]. AB - We report the results of a multicenter study performed on 70 patients with severe congestive heart failure of different etiology (ischemic, idiopathic, alcoholic, valvular and secondary to antiblastic drugs) to evaluate the clinical and hemodynamic effects and tolerability of low dose amrinone iv (0.75 mg bolus followed by a continuous 48-hour infusion at the dose of 5-10 mcg/kg/min). Forty one patients underwent invasive hemodynamic monitoring with right heart Swan-Ganz catheterization. Heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI), stroke work index (SWI), right atrial pressure (RAP), pulmonary wedge pressure (PWP), mean arterial pulmonary pressure (PAP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) were evaluated before and after 1, 4, 6, 24 and 48 hours of amrinone infusion and 2 and 4 hours after amrinone withdrawal. Clinical parameters (dyspnea, orthopnea, pulmonary congestion) were quantitated using a score; diuresis was assessed hourly; hematochemical parameters were evaluated before and 48 hours after amrinone infusion. HR and MAP were not significantly changed; CI, SVI and SWI presented, respectively, a significant 31.6, 55.1 and 72% increment, which peaked 48 hours after amrinone infusion. Concomitantly RAP, PAP, PWP, SVR, PVR and TPR were significantly reduced to 36.6, 22, 23.6, 9.4, 39.2 and 37.7% of the basal values, respectively. Two and 4 hours after amrinone withdrawal, hemodynamic changes similar to those observed acutely, were still present. Diuresis increased from 58.25 ml/hr to 113.18 ml/hr after 24 hours (+95%) and to 88.9 ml/hr (+53%) after 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756542 TI - [The usefulness of echocardiography in the diagnosis of prosthetic valve endocarditis: a comparison between the transthoracic and transesophageal approaches]. AB - Transesophageal echocardiography is a new semi-invasive procedure whose practical application has yet to be precisely defined. The diagnosis of prosthetic valve endocarditis is particularly difficult with the transthoracic approach, either by thoracic conformation of patients who underwent cardiac surgery, or ultrasound attenuation caused by the prosthetic material. Transesophageal echocardiography is useful to overcome such limits with a new acoustic window, due to the proximity of the esophagus and the heart. During 15 months 18 patients with suspected prosthetic valve endocarditis were studied using both procedures. In patients with mitral prosthetic valves, transesophageal echocardiography provided information unobtainable by using the transthoracic procedure, while in patients with aortic prosthetic valves it only showed additional information in 1 case of abscess of the posterior valve ring. In conclusion, transesophageal echocardiography is useful to diagnose all patients with suspected prosthetic mitral valve endocarditis and might be performed in patients with aortic valve prostheses if the quality of the transthoracic procedure is poor. PMID- 1756543 TI - [Heart arrhythmias in chronic respiratory failure due to chronic obstructive bronchopneumopathy: the incidence and correlations with nocturnal respiratory disorders]. AB - The aim of this study was to assess: frequency and type of cardiac arrhythmias in patients with severe stable chronic obstructive lung disease (COLD) and chronic respiratory failure (CRF); diurnal or nocturnal predominance of the detected arrhythmias; prospective relationships between arrhythmias and nocturnal hypoxemic-hypercapnic episodes. All patients were examined with careful and complete medical history, chest roentgenogram, standard electrocardiogram, mono and bidimensional echocardiogram, respiratory function tests, arterial blood gases at rest, 24-hour dynamic electrocardiographic recording and, simultaneously, transcutaneous nocturnal monitoring of respiratory gases (TCNM). We studied 14 men: all complained of exercise-induced dyspnoea for 8 +/- 6 years; 10 of them reported usual nocturnal snoring. Respiratory function tests provided the following values (expressed in percentage compared with theoretical ones): vital capacity 58.6 +/- 15, forced expiratory volume/s 36 +/- 19, Tiffeneau index 60 +/- 19, Motley index 160 +/- 35, carbon monoxide diffusion capacity 48 +/- 26. Arterial blood gas analysis at rest resulted: PO2 47 +/- 4.5 mmHg, PCO2 49 +/- 7.9 mmHg, pH 7.38 +/- 0.3. Right ventricular diameter obtained with mono and bidimensional echocardiogram was 32 +/- 4.6 mm. Right pulmonary descending artery measured on chest roentgenogram was 23 +/- 3.8 mm. Nocturnal transcutaneous monitoring of respiratory gases showed mean PO2 of 40 +/- 9.7 mmHg and mean PCO2 of 75 +/- 19 mmHg. During night-time maximum percentage reductions of PO2 (36 +/- 17%) were measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756544 TI - Effects of a cable car trip on blood pressure and cardiovascular hormones in lowlander and highlander normotensives. AB - The effects of a cable car trip from 1370 m (4500 ft) to 3460 m (11350 ft) were studied in 6 lowlanders (3 men and 3 women, mean age 31 +/- 4 years, living at an altitude of less than 500 m) and in 10 highlanders (all males, mean age 37 +/- 12 years, ski teachers and cable car workers working for greater than or equal to 6 months/year at a greater than 3000 m). Cuff blood pressure (BP), heart rate, plasma catecholamines, serum renin, aldosterone, ACTH and cortisol were measured immediately before and 20 min after the trip, at rest and at the same air temperature. A handgrip test was also performed under the same conditions. At baseline, lowlanders and highlanders showed significant differences in diastolic BP (86 +/- 5 mmHg in lowlanders and 91 +/- 4 mmHg in highlanders, p = 0.05), plasma noradrenaline (323 +/- 114 pg/ml in lowlanders and 585 +/- 255 in highlanders, p less than 0.05), serum renin (10 +/- 6 pg/ml in lowlanders and 17 +/- 8 in highlanders, p less than 0.05), and serum cortisol (163 +/- 54 ng/ml in lowlanders and 120 +/- 25 in highlanders, p less than 0.01). The acute exposure to high altitude did not modify BP, heart rate or any of the measured cardiovascular hormones in either group. The handgrip test provoked a significant increase in systolic and diastolic BP in both lowlanders and highlanders (p less than 0.01), and this response was not modified by the change in altitude; however, highlanders showed significantly smaller increases in systolic BP than lowlanders at both altitudes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756545 TI - [Permanent atrial standstill and atrial disease]. AB - A case of permanent atrial standstill suspected upon electrocardiogram is reported, and confirmed by electrophysiological investigation. The originality of this case resides in the fact that the atrial standstill marks the developmental outcome of a bradycardia-tachycardia syndrome. This developmental sequence is the subject on discussion. It is concluded that a combination of auricular muscle lesion and sinus node tissue remains the most plausible anatomical and pathophysiological substratum of the bradycardia-tachycardia syndrome which developed into atrial standstill. PMID- 1756546 TI - [Recent applications of informatics in postoperative intensive therapy in heart surgery]. PMID- 1756547 TI - Interventional radiology of the extracranial head and neck. AB - The topic of interventional radiology of the extracranial head and neck is reviewed. Knowledge of functional vascular anatomy and recognition of the "dangerous anastomoses" between the external carotid artery and the intracranial circulation are stressed. Technical aspects of embolization are surveyed. The authors' approach to some of the more common lesions such as paragangliomas, congenital vascular lesions, epistaxis, juvenile angiofibromas, and arteriovenous fistulas are described. Illustrative cases are presented. Proper training and experience are needed in order to safely and effectively perform embolization procedures of the head and neck. PMID- 1756548 TI - Urokinase thrombolysis using a multiple side hole multilumen infusion catheter. AB - A multilumen, multiple side hole infusion catheter was used for urokinase thrombolysis in 13 patients with thromboembolic occlusions of peripheral arteries and grafts. Balloon angioplasty was performed following urokinase infusion in 6 patients and atherectomy in 1 patient. There was one hemorrhagic complication. The major advantage of the multiple sidehole infusion catheter was the elimination of the need to reposition the catheter during the infusion and the reduction of the time burden on the angiographic facility. The success rate for the thrombolysis (77%) was comparable to results recorded in the literature. The total duration of infusion was not reduced compared to other series. PMID- 1756549 TI - Acute posttraumatic rupture of the thoracic aorta: the role of angiography in a 7 year review. AB - Between 1983 and 1989, 15 patients with acute rupture of the thoracic aorta by blunt trauma were seen. Superior mediastinal widening and obscuration of the aortic arch were the most important findings on chest radiograph. Computed tomography examinations in 7 patients showed mediastinal hematomas but did not reveal aortic lesions. Definitive diagnosis of traumatic aortic rupture was established by aortography in all 15 patients. Intraarterial digital subtraction angiography proved to be as accurate as conventional film aortography and saved time. PMID- 1756550 TI - Left femoral vein approach for the percutaneous placement of the Bird's Nest Filter. AB - The Bird's Nest Filter femoral catheter set has proven to be too short in some patients to permit placement in close proximity to the renal veins via the left femoral vein approach. The use of the longer, but otherwise identical Bird's Nest Filter jugular catheter set via the left femoral vein eliminates this problem. PMID- 1756551 TI - Massive hemoptysis from a pulmonary sequestration controlled by embolization of aberrant pulmonary arteries: case report. AB - A case of massive hemoptysis due to pulmonary sequestration is presented. Initially, the diagnosis of sequestration was unsuspected and bronchial artery embolization was done for management of hemoptysis from the left lower lobe, but 4 days later massive hemoptysis recurred. Repeat arteriography, including a thoracoabdominal aortogram, revealed two large abdominal arteries penetrating the left diaphragm and feeding the lower lung. Embolization of the aberrant artery from the celiac trunk and the left inferior phrenic artery resulted in complete hemostasis until elective surgical ligation of the two arteries was performed 2 months later. The massive hemoptysis from a pulmonary sequestration could only be controlled after embolization of the transdiaphragmatic aberrant pulmonary arteries. PMID- 1756552 TI - An aberrant right hepatic artery from the right renal artery: anatomical vignette. AB - The vascular supply of the liver is variable. An unusual aberrant right hepatic artery arising from the right renal artery is described. The embryologic derivation and clinical relevance are discussed. PMID- 1756553 TI - Successful thrombolysis of a chronically occluded femoropopliteal synthetic bypass graft via the popliteal approach: case report. AB - Thrombolysis of an occluded femoropopliteal synthetic bypass graft was performed via the popliteal artery approach for infusion catheter placement and urokinase delivery. Graft thrombolysis was achieved without complication. The proximal graft anastomosis could not be identified and prevented selective antegrade catheter placement and infusion. Because the distal graft anastomosis was visualized, the percutaneous popliteal approach was used. Subsequently, angioplasty was performed of an unmasked stenosis that presumably led to graft closure. We can conclude that selective thrombolysis via catheter placed from popliteal thrombolysis is an effective technique for recanalization of occluded femoropopliteal bypass grafts if the antegrade approach is not feasible. PMID- 1756555 TI - Morphologic change in coronary artery stenosis with the Medtronic Wiktor stent: initial results from the core laboratory for quantitative angiography. AB - The purpose of this study was to assess the early changes in stenosis geometry after implantation of the Medtronic Wiktor stent in human coronary arteries. Morphologic changes were evaluated by quantitative coronary angiography using automated edge detection. The hemodynamic significance of the morphologic changes were assessed by the calculation of the theoretical pressure drop across the dilated and stented stenosis derived from the Poiseuile and turbulent resistances assuming a coronary blood flow of either 0.5, 1, or 3 ml/sec. Fifty patients were studied before and immediately after stent implantation. The stented coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in eight patients, and the right coronary artery in 16 patients. Stent implantation resulted in an additional increase in the minimal luminal cross sectional area and minimal luminal diameter of the dilated vessel without changing the curvature of the stenosis. Furthermore, there was a significant reduction of the "plaque area." This was associated with a normalization of the calculated resistances to flow and pressure drop across the stenosis. To a minimal extent, recoil (0.1 +/- 0.36 mm) was observed after stent implantation. PMID- 1756554 TI - Catheter-guided intraoperative localization of a jejunal angiodysplasia using the Tracker-18 coaxial catheter system: case report. PMID- 1756556 TI - A solution to the problem of an unexpanded Palmaz-Schatz stent following balloon rupture. AB - The Palmaz-Schatz stent is a balloon expandable stent. Although easy to deploy, problems can occur. One problem is balloon rupture resulting in a partially expanded stent, which can be difficult to expand fully. This report illustrates how a Probing catheter and balloon can solve this potentially serious problem. PMID- 1756557 TI - Disruption of a coronary stent during atherectomy for restenosis. AB - Directional coronary atherectomy is being used in the treatment of atherosclerotic lesions in coronary vessels and vein grafts. This report describes the use of atherectomy for the treatment of restenosis of a coronary stent. The procedure was complicated by disruption of the stent which was snared by the atherectomy cutter. PMID- 1756558 TI - Intravascular stenting of the right internal mammary artery. AB - Despite its tortuous course and small caliber, percutaneous transluminal coronary angioplasty of the internal mammary artery can be performed with a high initial success rate (82-94%). The successful deployment of a balloon expandable coil stent at the mid-right internal mammary artery in a patient with recurrent stenosis of that graft is reported. PMID- 1756559 TI - Balloon expandable stent implantation of a stenosis at the origin of the left internal mammary artery graft: a case report. AB - We describe a case of percutaneous transluminal coronary angioplasty in which we implanted a balloon expandable Palmaz-Schatz stent into a high-grade restenosed lesion at the origin of the left internal mammary graft. PMID- 1756560 TI - Do stents interfere with the densitometric assessment of a coronary artery lesion? AB - This in vitro study was designed to assess the contribution of three currently investigated coronary stents to the densitometric measurement of a known stenosis contained within two different sized plexiglass phantoms. These studies were performed at two concentrations of the contrast agent iopamidol (50 and 100%). The calculated minimal luminal cross-sectional area values in the control phantom ranged from 0-18% higher than the theoretical values. Insertion of a stainless steel stent (Wallstent, Schneider, Zurich or Palmaz-Schatz, Johnson and Johnson, Warren, NJ) resulted in further minor increases (less than or equal to 8% in the calculated minimal luminal cross-sectional area, except in the smaller phantom filled with 50% contrast medium. The Wiktor (tantalum) stent (Medtronic, Minneapolis, MN) had the largest impact of the three stents depending on the concentration of iopamidol (100% contrast medium: 9-13% values above control; 50% contrast medium; 23-56% higher). We conclude that although densitometry may overestimate the minimal luminal cross-sectional area in stented vessels, this effect is usually minor with stainless steel stents. However, tantalum-containing stents may result in serious overestimation of lesion area, particularly if contrast is diluted or the vessel is not well filled. PMID- 1756561 TI - Aneurysmal saphenous vein graft presenting as an anterior mediastinal mass. AB - A 58-year-old male presented with an anterior mediastinal mass which was found to be secondary to an aneurysmal dilatation of the saphenous vein graft to his circumflex artery. This represents an unusual presentation of an aneurysmally dilated saphenous vein graft. PMID- 1756562 TI - Pulmonary varix: magnetic resonance findings. AB - The magnetic resonance appearance of a confluent-type pulmonary varix is correlated with computed tomography and angiographic findings. This case demonstrates the usefulness of magnetic resonance in the evaluation of cardiovascular lesions. PMID- 1756563 TI - Bilateral coronary artery to left ventricular fistulas. AB - Congenital coronary artery fistulas are important coronary artery anomalies. Bilateral coronary artery fistulas are very rare and coronary artery to left ventricular communications are even more infrequent. This report describes a patient with bilateral right and left coronary artery fistulas draining into a common channel and emptying into the left ventricular cavity. PMID- 1756564 TI - Coronary-subclavian steal: an unusual cause of angina pectoris after successful internal mammary-coronary artery bypass grafting. AB - Coronary-subclavian steal syndrome is a rare cause of angina pectoris after bypass grafting using the internal mammary artery. We report the 11th case in the literature and review the pathophysiology and treatment of this disorder. We also review appropriate screening for this possibly increasing, yet preventable disorder. PMID- 1756565 TI - Variations in blood supply to the anterior interventricular septum: incidence and possible clinical importance. AB - The variations of the blood supply to the anterior interventricular septum in a series of 1,089 patients are described. Special attention has been given to variations and frequency of occurrence of the septal perforators originating from the left anterior descending artery. These variations may have clinical significance in this era of coronary angioplasty and coronary bypass surgery. PMID- 1756566 TI - Intracoronary verapamil for the treatment of distal microvascular coronary artery spasm following PTCA. AB - Distal microvascular spasm is a somewhat uncommon occurrence following PTCA and often does not respond well to nitroglycerin. We report several patients who developed distal microvascular spasm that was refractory to intracoronary nitroglycerin but responded promptly to intracoronary verapamil. PMID- 1756567 TI - Pneumococcal pericarditis successfully treated with catheter drainage and intravenous antibiotics. AB - Bacterial pericarditis is commonly a disease of children for which the primary treatment is surgical drainage. We report the case of a 19-yr-old patient presenting with pneumococcal pericarditis and tamponade treated successfully with intrapericardial catheter drainage and intravenous antibiotics. The technical aspects are discussed. PMID- 1756568 TI - Percutaneous triple-valve balloon valvuloplasty in a pregnant woman. AB - A 22-yr-old pregnant woman with mitral, aortic, and tricuspid stenosis presented with accelerating dyspnea and shortness of breath at the end of her first trimester. She subsequently underwent percutaneous triple-valve balloon valvuloplasty at 22 weeks of gestation without complications and achieved marked clinical improvement. We conclude that percutaneous triple-valve balloon valvuloplasty represents an alternative treatment for mitral, aortic, and tricuspid stenosis in pregnant women with compromised cardiovascular status who do not wish to terminate their pregnancy. PMID- 1756569 TI - Rotational ablation of chronic coronary occlusions. AB - Rotational ablation was performed successfully in three chronic coronary occlusions. At 3 months follow-up, two of the three lesions were patent. These cases illustrate the overall advantages and unique technical aspects of this device. PMID- 1756570 TI - Effects of rotational atherectomy in normal canine coronary and diseased human cadaveric arteries: potential for plaque removal from distal, tortuous, and diffusely diseased vessels. AB - To test the hypothesis that tortuous, diseased vessels could be successfully treated with a flexible rotational atherectomy device we evaluated the BARD atherectomy device with quantitative angiography and histology in normal canine coronary arteries and diseased human below-knee amputation specimens. The mid left anterior descending and the circumflex vessels were treated in 4 dogs serially with 1 wk separating treatments. The acute and follow-up anterior descending artery size was unchanged (1.41 mm before, 1.39 mm after, and 1.59 mm at 1 week). Similar findings were obtained in the circumflex vessels. In 4 adult human amputated legs, diseased peroneal or tibial arteries were treated with a significant reduction in the percent luminal diameter stenosis from 62.75 prior to intervention to 36.5 following intervention (p = 0.021). The luminal diameter increased from 0.81 to 1.54 mm (p = 0.06). In 2 canine arteries there was histologic evidence of localized perforation of the arterial wall, but there was no angiographic evidence of perforation or dissection and no significant myocardial necrosis in the distribution of the treated vessels at 1 wk. The majority of the diseased human vessels demonstrated smoothly cut atheromas with sparing of the media. The rotational atherectomy catheter system holds promise for removal of plaque in relatively small, diffusely diseased, tortuous vessels. PMID- 1756571 TI - Flow support catheter for prolonged maintenance of coronary blood flow. AB - A newly designed flow support catheter with a supporting wire mesh cage which can be expanded into a tubular configuration and then readily reduced was evaluated in mongrel dogs. Regional myocardial blood flow (RMBF) was measured using the radioactive microsphere technique in the area of both balloon-denuded instrumented and control non-instrumented coronary arteries following placement of either a fixed-wire or a higher profile rapid exchange flow support catheter. At 5, 20, and 180 min following delivery and expansion of either device, RMBF was not significantly different in left ventricular subepicardium and subendocardium perfused by the instrumented vs. the control coronary arteries. Angiography demonstrated widely patent instrumented arteries in 15/18 dogs; in no dog was side branch occlusion observed. Significant cage thrombus deposition was seen angiographically in 3 animals causing temporary total coronary occlusion in 1. Following reduction and removal of the flow support catheter, vessel patency was present in all dogs. The flow support catheter is an effective endovascular stenting device capable of providing structural arterial support, while simultaneously maintaining distal coronary blood flow. It is envisioned that the primary application of this catheter will be to enable primary salvage of vessels acutely injured during coronary angioplasty, by "tacking up" intimal flaps for an extended period. It may also provide a bridge to emergency surgical revascularization. PMID- 1756572 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: pulsus alternans. PMID- 1756573 TI - Failure of stent delivery. PMID- 1756574 TI - "Intimate" double balloon coronary angioplasty with a single Y connector. PMID- 1756575 TI - Right heart catheterization utilizing a transseptal-type sheath in patients with severe pulmonary hypertension. PMID- 1756576 TI - The cytoplasmic domain of adherens-type junctions. PMID- 1756577 TI - The dynamic instability of microtubules is not modulated by alpha-tubulin tyrosinylation. AB - The tyrosinylation of chick brain alpha-tubulin and the effects of the tyrosinylation status on the assembly and dynamic instability of chick brain MAP2:tubulin microtubule protein have been examined. Each of the eight major alpha-isotypes can be tyrosinylated in vitro, irrespective of whether a C terminal tyrosine is genetically encoded. The extent of tyrosinylation is however limited to congruent to 0.3 mol.mol-1. The tyrosinylation status (0 vs. 0.3 mol.mol-1) has no effect on either the assembly kinetics of chick brain microtubule protein or on the rate of length redistribution following assembly and shearing. It is therefore unlikely that the tyrosinylation status directly affects the intrinsic stability of assembled microtubules since the rate of length redistribution is both a sensitive assay and a function of the kinetic parameters governing dynamic instability. PMID- 1756578 TI - Synchronous triggering of trout sperm is followed by an invariable set sequence of movement parameters whatever the incubation medium. AB - The movement of live trout spermatozoa is very brief (25 sec at 20 degrees C) and conditions have been developed to get synchronous initiation of sperm motility which allowed quantification of the major parameters of sperm movement during the motility phase. Recorded flagellar beat frequencies decreased steadily from values of 55 Hz at the beginning to 20 Hz at the end of the motility phase. Sperm forward velocities followed a similar pattern from 250 to 20 microns.sec-1 in the same conditions and the diameters of sperm trajectories were reduced from 370 to 40 microns. Thus none of the characteristics of sperm movement was constant during the motile phase which ended abruptly by a straightening of the flagella. The decrease in flagellar beat frequencies and sperm velocities are much greater than what could be extrapolated from the decrease of intracellular ATP (Christen R. et al: Eur. J. Biochem, 166: 667-671, 1987) or from measurements of ATP dependence of reactivated sperm velocities (Okuno M. and Morisawa N.: In Biological Functions of Microtubules and Related Structures. New York: Academic Press, pp. 151-162, 1982). Therefore, the cessation of flagellar beating at 25 sec is not directly the result of the low concentration of intracellular ATP. The decrease in the diameters of sperm trajectories which occurred during the first part of the motility phase was correlated with [Ca]i measurements (Cosson M.P. et al, Cell Motil. Cytoskeleton, 14:424-434, 1989). The effect of Ca2+ at the axonemal level does not indicates that Ca2+ influx is previous to flagellar beating but rather suggests a classical Ca2+ regulation of the flagellar assymetry. The short duration of the motility phase and the characteristics of sperm movement were very similar in various conditions (high external K+, low pH media) where increased external Ca2+ or divalent ions were shown to overcome K+ and H+ inhibition of sperm motility, both conditions which have been shown to depolarize the plasma membrane potential (Gatti J.L. et al: J. Cell Physiol., 143:546-554, 1990). The present study of the parameters of sperm movement suggests that once motility is initiated, a defined set of axonemal events will take place whatever the external conditions. PMID- 1756579 TI - Cloning, sequencing, and mapping of an alpha-actinin gene from the nematode Caenorhabditis elegans. AB - The dense-bodies in the body wall muscle of the nematode Caenorhabditis elegans function to anchor the actin thin filaments to the adjacent sarcolemma. One of the major components of the dense-bodies is the actin-binding protein alpha actinin. To facilitate a genetic analysis of alpha-actinin, we have cloned a cDNA encoding the nematode protein, identified its position on the nematode physical map, and developed a unique PCR based approach to test the position of the cloned gene relative to known genetic deletions. The peptide sequence deduced from the cDNA shows that, apart from a few exceptional regions, the nematode protein shows strong similarity to other known alpha-actinins. Its position on the genetic map shows that none of the known muscle affecting mutations identified in C. elegans are in this alpha-actinin gene. This gene has been given the name atn-1 (alpha actinin-1). PMID- 1756580 TI - Musculoskeletal disorders in the haemophilias. AB - The management of the haemophilias has been improved by the advent of potent consistent clotting factor replacement therapy. The previously lethal major complications such as intracerebral haemorrhage are now rare, and the infective complications of treatment, most notably hepatitis and AIDS, are now potentially preventable with the new synthetic products. There is also the prospect of 'cure' by gene insertion therapy. Advanced arthropathy has been minimized but not prevented by early effective treatment of haemarthroses, and there is a diminishing legacy of severely affected patients many of whom may require joint replacement surgery. The present group of such patients has a high prevalence of HIV-1 infection and an increased risk of joint sepsis. The available avenues of treatment for the subacute stage of the arthropathy have not been particularly effective, emphasizing the need to prevent recurrent bleeding. The development of a multidisciplinary team-management approach in centres of expertise has been a significant factor in the improved longevity, life satisfaction and preserved mobility now available to most haemophiliacs. PMID- 1756581 TI - Rheumatological complications of sickle cell disease. PMID- 1756582 TI - Rheumatological manifestations of the leukaemias and graft versus host disease. AB - Bone and joint involvement in the leukaemias is discussed. Particular emphasis is placed upon osteoarticular presentations which may predate the haematological changes or divert attention from the primary pathology. A description of acute and chronic graft versus host disease is presented with particular emphasis on the rheumatological manifestations. PMID- 1756583 TI - Henoch-Schonlein purpura. AB - Henoch-Schonlein purpura probably results from a reaction in a host sensitized by an infective stimulus. This stimulus leads to the synthesis of IgA antibody, the presence of circulating immune complexes and a leukoclastic vasculitis involving IgA resulting in renal and dermatological manifestations. The risk factors, the causal organism and the reason for the association with IgA nephropathy remain unknown. PMID- 1756584 TI - Adult-onset Still's disease. AB - Adult onset Still's disease seems to be the adult form of Still's disease in children. The key symptoms of the disease are high spiking fever, arthritis and a macular or maculopapular, salmon-pink evanescent rash, almost always accompanied by neutrophilic leukocytosis and frequently by sore throat, intense myalgias, lymphadenopathy, splenomegaly and signs of serositis. Tests for IgM rheumatoid factor and antinuclear antibody are characteristically negative. With respect to haematologic abnormalities, the disease may give rise to several problems. First, there is a neutrophilic leukocytosis, which currently is unexplained, and often a normocytic normochromic anaemia, that may be profound. The anaemia has the characteristics of anaemia of chronic inflammatory disease. Both abnormalities disappear after effective treatment of the disease or at spontaneous remission. Secondly, there might be a problem to differentiate AOSD from malignant haematological disorders, including malignant lymphoma and leukaemia, especially when the picture is dominated by lymphadenopathy, splenomegaly, fever and leukocytosis. Although in rare cases the differential diagnosis is extremely difficult, diagnosis can mostly be made or excluded by peripheral blood smear staining, bone marrow biopsies and occasionally lymph node biopsy. Finally, like the juvenile counterpart, AOSD is occasionally complicated by sometimes life threatening diffuse intravascular coagulation. Factors that might be important in the development of this complication include severe disease activity, liver abnormalities and particular drugs including salicylates, other NSAIDs and some slow-acting antirheumatic drugs. Prompt therapy, including withdrawal of the drug, corticosteroids and sometimes anticoagulant therapy have been successfully applied to most patients. PMID- 1756585 TI - Immunodeficiency and lymphoproliferative disorders. PMID- 1756586 TI - Multicentric reticulohistiocytosis: systemic macrophage disorder. AB - Multicentric reticulohistiocytosis is a rare multisystem disorder that reflects a reactive inflammatory response to an undetermined stimulus. While the disease is characterized as a dermatoarthritis, multiple organ systems including cardiac and skeletal muscle, the pleura and gastrointestinal tract have been involved in reported cases. The synovitis can be quite destructive with arthritis mutilans developing in a substantial percentage. The dermatitis may be particularly disfiguring when the face is involved. This chapter describes the clinical and laboratory features of the 33 cases of MRH previously reviewed by Barrow and Holubar and an additional 33 cases that have appeared in the medical literature since that report. We note an apparent decline in frequency of some manifestations of MRH. This may be due in part to the nature of the recent reports which often present a brief clinical report and focus primarily on specific disease associations, unusual manifestations, new organ system involvement or treatment regimens. The primary cell involved in the reactive inflammatory response of MRH is the phagocytic tissue histiocyte (macrophage). While uncontrolled proliferation of these reticulohistiocytes is seen in several infectious and malignant conditions there is presently no direct evidence of a particular organism or neoplasm involved in the aetiopathogenesis of MRH. There is evidence of tuberculosis exposure in one third of cases with active tuberculosis present in 5%. Likewise, malignancies are reported concomitantly with MRH in 15-28% of cases. The therapeutic trend in MRH is to treat early and aggressively to prevent the devastating arthropathy and disfiguring cutaneous sequelae. This recommendation, however, is largely based on anecdotal reports and thus the physician encountering a case of MRH needs to proceed with circumspection. PMID- 1756587 TI - Ehlers-Danlos syndrome. PMID- 1756588 TI - Rheumatic manifestations of haemochromatosis. AB - Haemochromatosis (HC) is a group of phenotypically heterogeneous clinical syndromes, which may have a common molecular basis. Classical genetic haemochromatosis (GHC) is one of these syndromes and is a disorder of iron storage due to an increase in intestinal iron absorption, which results in progressive and massive iron deposition leading to fibrosis and organ malfunction. The liver, pancreas, heart and pituitary are commonly involved. There is a specific arthropathy and an association with osteoporosis. Clinically, the arthropathy may resemble rheumatoid arthritis, with acute attacks of inflammation associated with bilateral destruction of the metacarpophalangeal joints. However, bony joint swelling may occur, suggestive of osteoarthritis. Hip arthritis may be unduly severe and disabling. Haemochromatosis arthritis is composed of three radiographic categories: isolated chondrocalcinosis, hypertrophic osteoarthritis which is indistinguishable from pyrophosphate associated arthropathy, and disease specific changes such as subchondral radiolucency of the femoral head, hook-like osteophytes on the metacarpal heads and a degenerative predilection for the metacarpophalangeal joint rather than the scapholunate. The characteristic histological changes are: abnormal amounts of iron deposits, little or no signs of synovial inflammation and CPPD deposition. Subchondral radiolucency of the femoral head and atypical stripping of the cartilage from the subchondral bone are thought to be specific radiographic and histological changes of HC. The pathogenesis of HC arthritis has been associated with the presence of iron in joint tissue, a defect in cartilage metabolism and immunological dysfunction. Treatment has little effect on clinical, radiological or histological progression. PMID- 1756589 TI - Some aspects of the use of dextran sulfate-cellulose columns for the treatment of familial hypercholesterolemia. PMID- 1756590 TI - A radiometric assay for aspartoacylase activity in human fibroblasts: application for the diagnosis of Canavan's disease. AB - A new sensitive method for measuring aspartoacylase activity in human skin fibroblasts using [3H]N-acetyl-L-aspartic acid (NAA) is described. Optimal assay conditions and kinetic parameters for enzyme activity were determined. The enzyme was found to have maximal activity at pH 8.5, and the Michaelis constant for the substrate N-acetylaspartate was 1.8-2.0 mmol/l. Aspartoacylase activity in control cultured human fibroblasts was 9.2 +/- 1.8 nmol/h per mg protein, compared with 1.1 +/- 0.2 in seven Canavan patients and 3.5 +/- 0.9 in four patients' parents. This method for determining aspartoacylase activity is advantageous to the previously described spectrophotometric method since it is rapid, more sensitive and has less nonspecific interference. It is possible that application of this technique to cultured ammniotic and chorionic villi cells may be used for prenatal diagnosis of Canavan's disease. PMID- 1756591 TI - Sensitive enzyme immunoassay for human 28 kDa calbindin-D. AB - A sandwich-type enzyme immunoassay for human 28 kDa vitamin D-dependent calcium binding protein (calbindin-D) was established with a sensitivity of 1 pg/tube. Antisera were generated in rabbits injected with highly purified human kidney calbindin-D, and specific antibodies to calbindin-D were purified by the use of a column of calbindin-D-coupled Sepharose. The purified antibodies showed a single band at the position corresponding to calbindin-D on an immunoblotting test with a crude extract of human kidney. The assay system consisted of polystyrene balls with immobilized F(ab')2 antibodies and the same antibodies labeled with beta-D galactosidase from Escherichia coli. The assay was specific to 28 kDa calbindin D, showing no cross-reactivity with other calcium binding proteins such as S 100a0 (alpha alpha), S-100b (beta beta), parvalbumin and calmodulin. The assay was also reproducible (coefficients of variation between assays were less than 10%). With the present method, immunoreactive calbindin-D could be detected in various human tissues, with major concentrations in kidney and brain. The values for immunoreactive calbindin-D in various body fluids of healthy subjects varied from undetectable in serum and semen to 3.8 +/- 2.0 (SD) micrograms/g creatinine in urine and 2.9 +/- 0.8 (SD) micrograms/l in cerebrospinal fluid. Immunohistochemically, the calbindin-D in human kidney was localized in epithelial cells of distal tubules. PMID- 1756592 TI - Brain natriuretic peptides in human plasma, spinal cord and cerebrospinal fluid. AB - In cases of heart failure, the plasma level of immunoreactive human brain natriuretic peptide (IR-hBNP) measured by radioimmunoassay increased 6- to 46 fold over normal level (4.1 +/- 1.0 pg/ml), depending upon the severity. These levels did not significantly correlate to the levels of IR-human atrial natriuretic peptide in individuals. A 4-kDa IR-hBNP, corresponding to authentic hBNP (1-32), was predominant in normal plasma. In cases of cardiac disease, larger molecules which were assumed to be precursors of the 4-kDa form were accumulated in plasma. IR-hBNP was detected in spinal cords (7-24 pg/mg protein) and cerebrospinal fluid (8-19 pg/ml) of patients with noncardiac diseases. The major molecular form corresponded to the hBNP (1-32). PMID- 1756593 TI - Anti-skeletal muscle and anti-acetylcholine receptor antibodies in patients with thymoma without myasthenia gravis: relation to the onset of myasthenia gravis. AB - We measured the anti-skeletal muscle (SM) antibody titers in sera from 46 patients with thymoma but without Myasthenia gravis (MG) in order to determine whether the presence of anti-SM antibody is linked to the combination of thymoma MG, or to thymoma alone. We detected anti-SM antibodies in 18 of these sera, of which 15 had concomitantly elevated titers of anti-AChR antibodies. Moreover, 9 of whom had experienced the onset of MG after surgery. In contrast, no patient without elevations in both antibodies developed MG during the followup. We conclude that the presence of anti-SM antibodies is linked strongly with thymoma associated with MG, but not with thymoma alone. PMID- 1756594 TI - Identification of human ventricular myosin heavy chain fragments with monoclonal antibody 2F4 in human sera after myocardial necrosis. AB - An ELISA assay with monoclonal antibody (Mab 2F4) raised against human ventricular myosin heavy chains was developed and used to investigate human sera after myocardial infarction. The monoclonal antibody 2F4 was selected for its high affinity to soluble fragments of myosin heavy chains (subfragment-1) and for its appropriate tissue specificity. By including Mab 2F4 in a simple and rapid dot immunobinding assay sera from patients with acute chest pain and of persons without a history of heart disease were tested. Myosin was detected only in the sera of the patients with myocardial necrosis, confirmed by electrocardiographic data. Negative reactions in all control cases were found. The serum myosin fragments reactive with Mab 2F4 were characterized by immunoblot experiments and protein bands in the region about 43 kDa were found. It was concluded that the myocardial infarction can be demonstrated by detection of cardiac myosin heavy chain fragments in the patients' sera. PMID- 1756595 TI - Immunonephelometric assay of myoglobin. PMID- 1756596 TI - Determination by latex immunoassay of protein 1 in normal and pathological urine. AB - A sensitive latex particle assay has been developed to study the occurrence of protein 1 in human urine. The coefficients of variation (CVs) of the method which is fully automated vary between 3 and 11.5%. The assayable concentration range is 0.3 to 40 micrograms/l. Protein 1 is clearly a sex-dependent protein. In contrast to urinary retinol-binding protein (RBP) which shows no variation with age or sex, protein 1 is excreted in greater amounts in males from the puberty. In adults, the mean concentration of protein 1 in urine of men is approximately 5 times that of women. In the urine from both sexes, protein 1 occurs as a single component with a Mr around 21,000 and an pI of about 4.8. Protein 1 is correlated with RBP in the urine from female or male patients with impaired proximal tubular function, which suggests that it is handled by the kidney in a similar manner as RBP. Diabetics, however, show elevations of urinary protein 1 which do not correlate with the RBP excretion but with the albuminuria. A competition between albumin and protein 1 for renal tubular uptake might explain this paradoxical behaviour of protein 1 in the course of diabetic nephropathy. PMID- 1756597 TI - Examination of the role of oxygen free radicals in bronchial asthma in childhood. AB - The antioxidant enzyme activities, the lipid peroxidation level, the parameters of glutathione metabolism, and the proportion of haemoglobin oxidation products were determined during the symptom-free period of childhood bronchial asthma. A decreased catalase activity and a significantly reduced glutathione instability were demonstrated as compared to the controls. The results indicate that antioxidant protection of the haemoglobin molecule in asthmatic children is considerably decreased. PMID- 1756598 TI - Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): the clinical variation and prenatal diagnosis. AB - Six patients with the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, namely five members of the same family and one sporadic case, are presented. One of the main features of the EEC syndrome, ectrodactyly, was missing in five of the patients. The diagnosis did not become clear until the youngest son of the family was born. All of our six patients had a low birth weight and some were born preterm, and four had poly- and/or syndactyly without ectrodactyly. A low birth weight and polysyndactyly have been reported previously in patients with the EEC syndrome and might be features of the syndrome. The present patients illustrate the great phenotypic variability in the EEC syndrome and the need for a careful search for microsymptoms in potential gene-carriers. In two members of the affected family, EEC syndrome was diagnosed prenatally after 16 weeks of gestation by detection of the cleft lip and palate on ultrasound examination. The mother chose to continue the pregnancies. However, prenatal diagnosis of cleft lip and palate might be of value in genetic counselling for other inherited syndromes leading to severe disability. PMID- 1756599 TI - Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks. AB - The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non-competitive Enzyme Linked-Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti-LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunophenotypes) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co-dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c-,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g-) genotype). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body-mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus. PMID- 1756600 TI - Saethre-Chotzen syndrome (ACS III) in four generations. AB - The acrocephalosyndactylies (ACS) are a group of inherited disorders characterized by premature fusion of cranial sutures in association with abnormalities of the hands and feet. Based on their clinical features, different types of ACS have been described. We here report on a family with 9 individuals affected with ACS III (Saethre-Chotzen syndrome), 5 of them severely. Clinical features of the patients are presented with regard to differential diagnostic delineations. PMID- 1756601 TI - Heterogeneity for mutations in medium chain acyl-CoA dehydrogenase deficiency in the UK population. AB - MCAD is the commonest inherited disorder of fatty acid oxidation. We have sought for and studied 21 affected children from 18 families within the UK. In 14 families the children are homozygous for the G985 mutation. In three families the children are compound heterozygotes for G985 and thus carry another and unknown mutation. In one family the child does not carry the G985 mutation on either allele. The carrier incidence of the G985 mutation is 1 in 68, which suggests that the natural history of MCAD deficiency deserves further study. PMID- 1756602 TI - Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St-Jean (Quebec, Canada). AB - Cystic fibrosis (CF) is an autosomal recessive disorder with a prevalence at birth estimated at 1/2000-1/2500 livebirths in Caucasian populations. Some 127 CF individuals are known in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec. The prevalence at birth was estimated at 1/902 live borns, and the carrier rate was estimated at 1/15 inhabitants in the SLSJ region. The mean inbreeding coefficient was only slightly elevated in the CF group compared with three control groups, and was due to remote consanguinity. The mean kinship coefficient was 2.4 times higher in the CF group than in the control groups. In SLSJ region, the places of origin of the CF individuals and their parents did not show a clustered nonuniform distribution. Endogamy was not higher in the CF group than in control groups. PMID- 1756603 TI - Usher syndrome: results of a screening program in Colombia. AB - Otological, ophthalmological and genetic studies were performed in 46 patients with Usher syndrome, identified through a screening program in Colombia. Of them, 69.6% had Usher syndrome type I, 26.1% type II, and 4.3% type III. Thirty-three patients showed profound deafness (71.7%), while 13 (28.3%) had moderate to severe hearing loss. The ophthalmologic manifestations showed marked variability. Although the majority of the patients had serious ocular impairment before age 20, 32.6% had good central visual acuity. The prevalence of Usher syndrome in Colombia, estimated at 3.2/100,000, warrants the implementation of screening programs in schools for the deaf and for the blind. Our study confirms that Usher syndrome shows no geographic or racial variation and that the disorder has a wide variability of expression and genetic heterogeneity. The large size of the families we have detected may provide important opportunities for further genetic studies, particularly in terms of the assignment of the locus and gene mapping. PMID- 1756604 TI - Two Japanese cases with aspartylglycosaminuria: clinical and morphological features. AB - Two members of a consanguineous Japanese family with a clinical picture of aspartylglycosaminuria (AGU) are described. Both patients exhibited mental retardation, coarse facial features, angiokeratoma and myoclonic seizures. Biochemical studies showed elevated excretion of urinary sialyloligosaccharides and decreased activity of aspartylglycosaminidase in lymphoblasts. Morphologic studies of skin biopsy specimens showed many clear vacuoles mainly in the vascular endothelial cells and secretory cells of the sweat glands. Osmiophilic lamellar cytoplasmic inclusions were also noted in the ganglion cells in rectal biopsy. The ethnic distribution of AGU may be more widespread than previously suspected and appears not to be restricted to Finnish populations. Ours are the first Japanese patients diagnosed as AGU. We conclude that AGU should also be included in the differential diagnosis of mentally retarded patients in Asian countries. PMID- 1756605 TI - Tuberous sclerosis in a child with de novo translocation t(3;12) (p26.3;q23.3). AB - We report on an 8-year-old boy with severe mental retardation, epileptic seizures, autistic behaviour, and X-ray CT findings of the skull characteristics for tuberous sclerosis. At the age of 9 years, first signs of adenoma sebaceum developed. Chromosomal analysis revealed a translocation t(3;12)(p26.3;q23.3). The parents were both healthy and had normal karyotypes. As non-random association of a chromosomal abnormality and tuberous sclerosis is hypothesized, a third locus for this disorder on 3p26 or 12q23 has to be taken in account. PMID- 1756606 TI - Familial Caffey's disease and late recurrence in a child. AB - Cortical Infantile Hyperostosis (Caffey's disease) is a benign and self-limited disorder. Late recurrence or persistence of symptoms with deformity seems exceedingly rare. Its occurrence in isolated cases or in multiple members in families suggests the existence of two different forms, namely a sporadic form and a familial form. The tibia is the predominant bone known to be affected in the familial form, while the mandible is mostly affected in the sporadic form. The different pathological processes found in these two forms add further to the heterogeneity of this disorder. We describe an Arabic-Christian, non consanguineous family with two affected sibs. In one, recurrent Caffey's disease was diagnosed at the age of 11 years. PMID- 1756607 TI - X-linked mental retardation with bilateral clasped thumbs: report of another affected family. AB - A Sephardi Jewish family is reported in which the two brothers had mental retardation, lower limb spasticity and bilateral clasped thumbs anomaly. This X linked recessive disorder has only been reported twice. We believe this syndrome comprises a distinct entity among the X-linked mental retardation syndromes. PMID- 1756608 TI - Nasopalpebral lipoma-coloboma syndrome. AB - An autosomal dominant dysplasia-malformation syndrome affecting seven individuals in one family is reported. The components of the syndrome include congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. It appears to be the second recorded example resulting from an autosomal dominant gene fully penetrant in both sexes. PMID- 1756609 TI - Endocrine and exocrine pancreatic function and the delta F508 mutation in cystic fibrosis. AB - The relationship between the cystic fibrosis (CF) genotype and endocrine and exocrine pancreatic function was studied in 215 CF patients. In the 211 patients with the delta F508 mutation, endocrine pancreatic function (oral glucose tolerance; WHO criteria) was normal in 72.5%, impaired in 12.3%, and diabetic in 15.2% of the patients, with no difference between CF patients homozygous (N = 163, median age 15 years, range 2-40) or heterozygous (N = 48, 18 years, 3-40; age difference not significant) for the delta F508 mutation. Exocrine pancreatic sufficiency (no need for pancreatic enzyme substitution) was found in 0.6% of the patients homozygous for the delta F508 mutation and in 10.4% of the heterozygotes (p less than 0.01). Homozygous patients with pancreatic insufficiency took more pancreatic enzyme capsules (median 42 per day, range 0-192) than the heterozygotes (29 per day, 0-300; p less than 0.001). The four patients (1.9%) without the delta F508 mutation had normal glucose tolerance but exocrine pancreatic insufficiency. In conclusion, the major mutation genotype in CF (delta F508) affects the severity of the exocrine pancreatic insufficiency, whereas endocrine pancreatic function is unrelated to this genotype. PMID- 1756610 TI - Apparent Fryns' syndrome and aneuploidy: evidence for a disturbance of the midline developmental field. AB - A premature male infant is described in whom the presence of coarse facies, diaphragmatic hernia, genital anomalies and Dandy-Walker malformation suggested a diagnosis of Fryns' syndrome. Lymphocyte karyotype revealed a partial trisomy 22, and his mother carried an apparently balanced 11/22 translocation. Three infants have been described recently with features of Fryns' syndrome and various aneuploidies. It is suggested that amplified developmental instability of the midline developmental field may account for some of the phenotypic resemblances between these cases. PMID- 1756611 TI - Mosaic tetraploidy in a liveborn infant with features of the DiGeorge anomaly. AB - We report on a liveborn male infant with mosaic tetraploidy who presented with multiple congenital anomalies including features of the DiGeorge anomaly (type I truncus arteriosus with other cardiovascular malformations, thymic hypoplasia, hypocalcemia). No structural chromosome aberrations, namely of chromosome 22, were detected. These findings contribute to the variability of symptoms of the polyploid phenotype. Additionally, the cytogenetic studies in our case emphasize the necessity of investigating fibroblasts in order to evaluate the relevant proportion of aberrant cells in mosaicism. PMID- 1756612 TI - Egg white proteins. AB - 1. Egg white proteins are the principal solutes present in egg white, making up approximately 10% of its weight. 2. They are globular proteins and most have acidic isoelectric points. 3. Many are glycoproteins with carbohydrate contents ranging from 2 to 58%. 4. Of the major egg white proteins, lysozyme is the only one having catalytic activity, but many have specific binding sites, e.g. for vitamins such as biotin, riboflavin and thiamin, or for metal ions such as FeIII. 5. A major group are those showing proteinase inhibitory activity, and they include ovomucoid, ovoinhibitor, cystatin and ovostatin. 6. The synthesis of egg white protein occurs in the oviduct, and is hormonally controlled either by oestrogens or progesterone. 7. Extensive studies have been carried out in the genes coding for egg white proteins. PMID- 1756613 TI - Equine testicular aromatase: substrates specificity and kinetic characteristics. AB - 1. In the stallion, estrogens were synthesized and sulfated in vivo by the testis. 2. The equine testicular enzyme aromatized androgens and 19-norandrogens with similar velocity, but not 16 alpha-hydroxytestosterone or epitestosterone in contrast to the human placental aromatase. 3. One single enzyme was implicated in the aromatization of androstenedione, testosterone, 19-norandrostenedione and 19 nortestosterone by ETMES. 4. During the process of androstenedione aromatization by ETMES, 19-hydroxyandrostenedione and 19-oxoandrostenedione were released and 4 hydroxyandrostenedione was a competitive inhibitor causing an additional irreversible enzyme inactivation which is what occurs with HPMES. 5. Dihydrotestosterone was a potent competitive inhibitor of aromatase activity. PMID- 1756614 TI - Comparative chromatography of Brazilian coral snake (Micrurus) venoms. AB - 1. Elution profiles of 11 coral snake venoms, including those of Micrurus albicinctus, M. corallinus, M. frontalis altirostris, M. f. brasiliensis, M. f. frontalis, M. fulvius fulvius, M. ibiboboca, M. lemniscatus ssp., M. rondonianus, M. spixii spixii and M. surinamensis surinamensis, were compared using high performance gel filtration and reverse phase media. 2. Micrurus venom profiles were compared with those of "outgroup" taxa Bothrops moojeni, Naja naja kaouthia and Bungarus multicinctus. 3. Purified elapid venom constituents were also chromatographed under identical conditions in order to suggest possible identities of Micrurus venom constituents. 4. Masses of various components were confirmed by mass spectrometry. 5. Phospholipase constituents in three venoms were positively identified based on their reverse phase chromatograms. 6. Venoms of M. rondonianus and M. s. surinamensis are shown to be significantly different in their peptide composition from other Micrurus venoms. PMID- 1756615 TI - A comparative study of bile acid CoA:amino acid:N-acyltransferase (BAT) from four mammalian species. AB - 1. Bile acid CoA:amino acid:N-acyltransferase (BAT) was partially purified from dog, human, pig and rat livers. The interspecies variation in substrate specificity and kinetics were determined for glycine and taurine. 2. BAT activity from dog liver formed bile acid conjugates with taurine exclusively, whereas BAT activity from each of the other species formed conjugates with both taurine and glycine. 3. Biliary composition of glycine and taurine bile acid conjugates could partly be accounted for by substrate affinity (Km) and turnover number (Vmax) of BAT activity. 4. A monospecific anti-human BAT polyclonal antibody reacted on Western blot analysis with a 40 kDa band in a 100,000 g supernatant fraction from rat liver. 5. Immunoabsorption chromatography using an anti-human BAT antibody Sepharose affinity column showed that both the immunoreactive protein band and BAT activity were removed from the 100,000 g supernatant fraction from human and rat livers. PMID- 1756616 TI - Comparison of glycosidase activities in epidermis, palatal epithelium and buccal epithelium. AB - 1. beta-Glucosidase, alpha-glucosidase, beta-galactosidase and alpha-mannosidase were measured in epidermis, palatal and buccal epithelium of the pig (Sus scrofa). 2. All three epithelia contained similar alpha-mannosidase activity (1.7 3.2 nmol mg tissue-1 hr-1 at pH 4), and none contained significant alpha glucosidase. 3. Specific activity of beta-glucosidase was high (9-13 nmol mg tissue-1 hr-1 at pH 4) in epidermis and palate, but activity was low (less than 2 nmol mg tissue-1 hr-1) in buccal epithelium. 4. Only epidermis contained a high level of beta-galactosidase (5.8 nmol mg tissue-1 hr-1). 5. Differences in glycosidase profiles may underlie differences in permeability barrier properties in these epithelia. PMID- 1756617 TI - Glucose entry rate in dairy cattle as determined by stable isotope 13C-labelled glucose at different stages of reproduction. AB - 1. Uniformly labelled stable 13C-glucose was used to study glucose entry in high yielding Holstein cows (n = 8) under normal production conditions. 2. The single injection technique was repeated at three different reproductive phases. A two compartment model was applied to calculate mean entry rates of glucose resulting in: (1) Terminal phase of pregnancy (2 weeks a.p.): 0.41 g/hr/kg0.75; (2) Peak lactation (6 weeks p.p.): 0.97 g/hr/kg0.75; (3) End of lactation (37 weeks p.p.): 0.61 g/hr/kg0.75. 3. Data from studies using radioactively labelled tracers are in good agreement with our results obtained without any restrictions implied by the handling with radioactive substances. PMID- 1756618 TI - Chemical structures of three neutral oligosaccharides obtained from horse (thoroughbred) colostrum. AB - 1. Three neutral oligosaccharides were obtained from horse colostrum by ion exchange, activated charcoal column and preparative paper chromatographies. 2. The following structures were elucidated by methanolysis, methylation analysis and 75 MHz 13C-NMR spectroscopy; Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc (HM 3a), Gal beta 1-4GlcNAc beta 1-6Gal beta 1-4Glc (HM-3b) and Gal beta 1-4GlcNAc beta 1-3[Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4Glc (HM-5). 3. HM-3a and HM-5 have been found in human milk, named as lacto-N-neotetraose and lacto-N neohexaose, respectively. HM-3b has been isolated from goat milk. 4. An homology and heterogeneity were assumed among the following animal species' milk oligosaccharides: horse, human, goat and tammar wallaby. PMID- 1756619 TI - Species-specific antibodies of Tetrahymena acid alpha-glucosidase. AB - 1. Tetrahymena acid alpha-glucosidases A and B were purified from T. pyriformis W and T. thermophila 399, respectively. The acid alpha-glucosidases A and B were different in immunological properties and thermostability. 2. The acid alpha glucosidases A and B reflected specific distribution between T. pyriformis and T. thermophila. 3. Type A and B of taurolipid showed a species-specific distribution pattern between T. pyriformis and T. thermophila. PMID- 1756620 TI - Is the "mammalian" brown fat-specific mitochondrial uncoupling protein present in adipose tissues of birds? AB - 1. Mitochondria were isolated from the furcular, subcutaneous, abdominal, nape and lateral adipose tissue depots of five species of bird (pheasant, Japanese quail, pigeon, house sparrow and great tit) acclimatized to the Northern winter. 2. Mitochondrial proteins were separated by SDS-polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes, and probed for the presence of the 32,000-33,000 Mr uncoupling protein characteristic of "mammalian" brown adipose tissue, using an anti-(ground squirrel uncoupling protein)serum. 3. Immunoreactivity consistent with uncoupling protein was not detected in mitochondria from any of the avian adipose tissues. Immunoreactivity was, however, evident in mitochondria from perirenal or interscapular adipose tissue from a range of mammals--rats, mice, golden hamsters, Orkney voles, wood mice, pipistrelle bats, wood lemmings, and newborn lambs, cattle, reindeer and red deer. 4. These results provide biochemical evidence that "mammalian-like" thermogenic brown adipose tissue is absent from avian species; adipose tissues in birds appear to be functionally "white". PMID- 1756621 TI - Regional differences in content of small basic peptide toxins in the venoms of Crotalus adamanteus and Crotalus horridus. AB - 1. Reverse-phase HPLC and organic solvents were used to isolate small basic peptide (SBP) toxins from the venoms of Crotalus adamanteus, C. durissus terrificus, C. horridus, C. scutulatus scutulatus, C. viridis concolor, C. viridis helleri and C. viridis viridis. 2. Acid-DEP analyses indicated a high degree of toxin purity which was obtained with a single HPLC run. 3. The combined results of HPLC, immunodiffusion and electrophoresis analyses of venoms from different geographical regions indicate that the SBP toxin content in the venoms of Crotalus adamanteus, Crotalus horridus, Crotalus scutulatus and Crotalus viridis viridis may vary regionally. PMID- 1756622 TI - A comparative study of the structure of egg-white riboflavin binding protein from the domestic fowl and Japanese quail. AB - 1. The riboflavin binding proteins from domestic fowl and Japanese quail have been isolated and their structures compared by circular dichroism, fluorescence and peptide mapping. 2. The two proteins have similar secondary structures, but differ in their tertiary structures as reflected in the environments of aromatic amino acid side chains. 3. Differences in amino acid sequence between the proteins are indicated by the digestion patterns obtained with thermolysin, chymotrypsin and V8 proteinase from Staphylococcus aureus. Both proteins are resistant to digestion by trypsin. PMID- 1756623 TI - The major glutathione S-transferase in salmonid fish livers is homologous to the mammalian pi-class GST. AB - 1. The hepatic glutathione S-transferase (GST) isoenzymes were isolated and characterized from salmon, sea trout and rainbow trout. 2. In all three species the predominant GST expressed comprised subunits of Mr 24,800. These subunits each co-migrated with the rat pi-class Yf polypeptide during SDS/polyacrylamide gel electrophoresis. 3. Western blotting experiments demonstrated immunochemical cross-reactivity between the major salmonid and the rat pi-class GSTs. 4. The salmon GST of subunit Mr 24,800 was digested with cyanogen bromide and the peptides, once purified by reverse-phase HPLC, were subjected to automated amino acid sequencing. 5. Over the region sequenced, the salmon GST possessed about 65% homology with the rat and human pi-class GST. PMID- 1756624 TI - The Nova-T IUD--a review of the literature. AB - The Nova-T IUD is being widely used in Western Europe, Canada, and some parts of Asia; numerous studies based on comparative trials with other types of IUDs have been reported. The results were consistent among most studies, but conflicting among others. This review paper revealed that, in general, the Nova-T IUD is a safe, effective, and acceptable device for contraception. However, more comparative studies with the other copper-releasing IUDs are needed to resolve some of the controversial findings on its long-term (e.g., five years or more) efficacy, especially with the TCu 380A which has the prospect of being used worldwide. The epidemiological (e.g., effects of age, parity, and lactating status of the women) and programmatic aspects (e.g., provider factors and timing of insertion) related to the performance of this device are also reviewed in this paper. PMID- 1756625 TI - Observation of the activity of factor VIII in the endometrium of women pre- and post-insertion of three types of IUDs. AB - The endometrial materials were obtained from 90 women who had been randomly inserted with three types of IUDs (Stainless steel ring, SS; copper T 220, TCu 220, and levonorgestrel-releasing device, LNG). An immunoperoxidase reaction, PAP method, with the antiserum of Factor VIII as the primary antibody, was carried out to detect the Factor VIII activity in the endometrial endothelium pre- (control) and post-insertion of the IUDs. The results revealed that: 1. There was a generalized lower Factor VIII activity in the endometrium of women post insertion of IUDs (except LNG). 2. Comparison of the Factor VIII activity in the endometrium of women using different types of IUDs showed that the TCu type and the SS type decreased the activity significantly whereas the activity remained unchanged after 3-6 months' use of the LNG-IUD. The different types of IUDs seemed to influence the coagulation regulatory system in different ways; the lower Factor VIII activity, the more tendency to bleeding. 3. The Factor VIII activity in the endometrium of women using IUDs was lower in all phases of the menstrual cycle including the proliferative phase when the Factor VIII activity is normally high. It cannot be excluded that this could be a contributing factor to IUD-induced bleedings. PMID- 1756626 TI - Effect of tarnish on copper release. AB - The rate of copper loss from bright and tarnished collars from Copper T Model TCu 380A IUDs has been investigated in amino acid solutions of pH 5.5 and 7.4 and in serum. In all three media, the tarnished collars quickly became bright and lost copper at the same rate as the initially bright collars. The single exception was when a high ratio of copper surface to serum was used. Under those conditions the tarnished collars initially became bright but after two days a black precipitate appeared on both the initially bright and tarnished collars and weight loss ceased. When a higher ratio of serum to copper surface was used, the pattern was one of continuing loss although at a lower rate than in the amino acid solutions. It is concluded that tarnish does not compromise the oxidation and dissolution of copper even in serum. Serum is considered a surrogate for uterine fluid. PMID- 1756628 TI - Phase II--clinical trial with biodegradable subdermal contraceptive implant Capronor (4.0-cm single implant). Indian Council of Medical Research Task Force on Hormonal Contraception. AB - The subdermal biodegradable contraceptive implant Capronor (4.0 cm) was implanted in 41 women to observe the efficacy and side effects. Only one pregnancy was reported at 10 months of use, and the life table continuation rate at 12 months was 82.2 per 100 users. No serious clinical side effects were reported during the study period. The menstrual pattern was disrupted during the first 3 months of implant use in two-thirds of the women which improved by the end of 12 months of use. The results of this Phase II study suggest that Capronor is a safe and effective long-acting contraceptive. These findings need to be confirmed in a Phase III clinical trial on a larger sample size. PMID- 1756627 TI - Clinical trial with 3-keto-desogestrel subdermal implants. AB - The study was done to assess the clinical performance and in vivo steroid release rate of 3-keto-desogestrel subdermal implants designed to deliver 5 different doses of the progestin. Volunteers were healthy women of proven fertility who provided blood samples at scheduled intervals during treatment. No pregnancy occurred in 514 woman-months in users of implants delivering 30 and 40 micrograms per day of 3-keto-desogestrel. Three pregnancies, one ectopic, were observed in 109 woman-months recorded with implants delivering 20 micrograms per day or less. Ovulation was inhibited, as judged by depressed progesterone levels, in 57 of 59 (97%) blood samplings in women whose 3-keto-desogestrel plasma levels were greater than 0.28 nmol/L and in 39 of 75 (52%) of cases with lower levels. Users of 4 cm implants manufactured by The Population Council, New York, showed mean levels above 0.28 nmol/L until 18 months of use. Levels achieved with 4.4 cm implants manufactured by Organon, Oss, Holland, were less consistent. No changes were observed in the plasma lipoprotein pattern or clinical chemistry during treatment. The main complaint was the occurrence of bleeding irregularities, particularly with the lower doses. Ovarian cysts found during pelvic examination in 11 (22%) subjects disappeared spontaneously within 7-90 days. 3-keto desogestrel implants releasing around 40 ug/day and providing plasma levels around 0.28 nmol/L afford efficient contraceptive protection. PMID- 1756629 TI - Contraception and sexuality in an area-specific group of Swedish women 15-34 years of age. AB - In a community-based study in a Swedish suburban/rural area, all women aged 15-34 years (n = 671) were invited to the local health centre to be examined for chlamydia infection and for an interview. The attenders were asked about contraceptive history, age at first intercourse, number of life-time sexual partners and socioeconomic background. The net attendance was 69%, and contraceptive information on an additional 20% could be gathered through medical records. The average age at first intercourse was around 16 years, and the average number of sexual partners in the age-groups 20-24, 25-30 and 31-34 years was 4.0, 5.6 and 6.1, respectively. Of all women, around 75% had used contraception at first intercourse, and there was no tendency to a changing pattern during the past 20 years studies through the interviews. Combined estrogen-progestagen pills were by far the most used contraceptive method, presently being used by 42% of the contracepting women, followed by condom (23%), IUD (19%) and other hormonal methods (10%). It is concluded that sexual life in Sweden starts earlier than it did 30 years ago, that the number of sexual partners is higher, that most women in the studied group were efficient contraceptors, and that hormonal contraception was by far the most common method. PMID- 1756631 TI - Valproate-induced alterations of coenzyme A and coenzyme A ester concentrations in human kidney tubules metabolizing glutamine. PMID- 1756630 TI - Use of hCG stimulation test in women immunized with beta-hCG vaccine. AB - Eleven normally menstruating women, who had earlier been immunized with NII beta hCG vaccine but had no detectable anti-hCG antibody titres, were selected as controls for the hCG challenge test using 1000/2000 I.U. The test was repeated in five of them after a booster immunization, which raised antibody titres to 18-450 ng/ml. Stimulation of serum progesterone secretion was used as an index of corpus luteum (CL) response to the I.V. hCG. In the control group, the progesterone (P) secretory response following hCG stimulus showed peak levels which were significantly higher than basal levels in all except 2 subjects. The non responsiveness in 2 subjects cannot be easily explained but may be dose-related. No significant difference was noted between the two dose levels. Length of luteal phase was increased by 4-5 days in 6 out of 20 cycles studied. The results of this test in 5 women before and after the vaccine boosters were encouraging as peak P levels appeared higher than basal levels in controls, but not so in the immunized group. However, these results could not be confirmed statistically. Nonetheless, this study is suggestive that the antibodies generated by this vaccine were capable of intercepting the effect of exogenous hCG in the human female. Further studies with more subjects and higher dosage of hCG are called for. PMID- 1756632 TI - Determinants of the partition of renal ammonia production between urine and venous blood in man with metabolic acid-base disturbances. PMID- 1756633 TI - Renal ammoniagenesis in man with chronic potassium depletion. PMID- 1756634 TI - Regulation of renal medullary ammonium accumulation. PMID- 1756635 TI - Changes in rat renal glutaminase activity on isolation from the mitochondrial membrane. PMID- 1756636 TI - Mapping ammoniagenic enzyme activities along the rat nephron. PMID- 1756637 TI - Ammonia production and secretion by the proximal tubule: effect of peritubular and luminal potassium concentration. PMID- 1756638 TI - Brain glutaminase activated by short-term microwave irradiation. PMID- 1756639 TI - Interactions between cell volume and hepatic nitrogen metabolism. PMID- 1756640 TI - Acute and chronic metabolic acidosis in the pig: renal metabolism and ammoniagenesis. PMID- 1756641 TI - Regulation of acetylglutamate in the liver: effect of glucocorticoid and renal failure. PMID- 1756642 TI - Nitrogen-15 NMR: a new technique for the study of renal nitrogen metabolism. PMID- 1756643 TI - Effect of acidosis on phosphoenolpyruvate carboxykinase and glutaminase mRNAs in rat kidney and in LLC-PK-F+ cells. PMID- 1756644 TI - Structure and expression of genes for urea cycle enzymes. PMID- 1756645 TI - Metabolic interactions between renal proline and glutamine metabolism. PMID- 1756646 TI - Evidence that the transport of glutamine into pig renal mitochondria is not rate limiting for glutamine hydrolysis. PMID- 1756647 TI - The significance of the purine nucleotide cycle in metabolism of renal medulla. PMID- 1756648 TI - Biochemical and anatomic evidence for renal tubule hypermetabolism and hypertrophy in long-standing experimental diabetes mellitus. PMID- 1756649 TI - The role of ammonia in progressive renal injury. PMID- 1756650 TI - Studies on the maleic acid-induced Fanconi syndrome in the rat: mechanism of phosphaturia and its mitigation by dietary phosphate restriction. PMID- 1756651 TI - Hepatic and renal regulation of metabolite flow in the remnant kidney model of chronic renal failure. PMID- 1756652 TI - Traumatic heart disease. PMID- 1756653 TI - Caught between parents: adolescents' experience in divorced homes. AB - This study examined adolescents' feelings of being caught between parents to see whether this construct helps to explain (1) variability in their postdivorce adjustment and (2) associations between family/child characteristics and adolescent adjustment. Adolescents 10 to 18 years old (N = 522) were interviewed by telephone 4 1/2 years after their parents' separation. Feeling caught between parents was related to high parental conflict and hostility and low parental cooperation. Being close to both parents was associated with low feelings of being caught. The relation between time spent with each parent and feeling caught depended on the coparenting relationship. Adolescents in dual residence were especially likely to feel caught when parents were in high conflict, and especially unlikely to feel caught when parents cooperated. Feeling caught was related to poor adjustment outcomes. Parental conflict was only related to adjustment outcomes indirectly, through adolescents' feelings of being caught. PMID- 1756654 TI - Conflictive engagement, positive affect, and menarche in families with seventh grade girls. AB - Prior research has established that temporary perturbations characterize parent daughter relations around menarche. This study was designed to determine whether the observed perturbations are indicative of conflictive engagement, operationally defined as sequential reciprocity of interruptions and disagreements, and to examine the affective nature of such behaviors. Sequential analyses were applied to the observed behavior of 111 intact families with firstborn seventh-grade girls (modal age = 12 years old) who participated in a structured family interaction task. Results indicated that conflictive engagement with parents is more frequent shortly after menarche, especially in the mother daughter dyad. Withdrawal of positive affect also was associated with menarcheal status; in the mother-daughter dyad, interruptions and disagreements were less often responded to with positive affect for the more mature groups. It is suggested that because of the nature of the interpersonal and intrapsychic processes occurring in the family around menarche, conflict may facilitate familial adaptation to pubertal change and make moderate levels of conflict normative in healthy families. PMID- 1756655 TI - Patterns of competence and adjustment among adolescents from authoritative, authoritarian, indulgent, and neglectful families. AB - In order to test Maccoby and Martin's revision of Baumrind's conceptual framework, the families of approximately 4,100 14-18-year-olds were classified into 1 of 4 groups (authoritative, authoritarian, indulgent, or neglectful) on the basis of the adolescents' ratings of their parents on 2 dimensions: acceptance/involvement and strictness/supervision. The youngsters were then contrasted along 4 sets of outcomes: psychosocial development, school achievement, internalized distress, and problem behavior. Results indicate that adolescents who characterize their parents as authoritative score highest on measures of psychosocial competence and lowest on measures of psychological and behavioral dysfunction; the reverse is true for adolescents who describe their parents as neglectful. Adolescents whose parents are characterized as authoritarian score reasonably well on measures indexing obedience and conformity to the standards of adults but have relatively poorer self-conceptions than other youngsters. In contrast, adolescents from indulgent homes evidence a strong sense of self-confidence but report a higher frequency of substance abuse and school misconduct and are less engaged in school. The results provide support for Maccoby and Martin's framework and indicate the need to distinguish between two types of "permissive" families: those that are indulgent and those that are neglectful. PMID- 1756656 TI - Relations between social competence and academic achievement in early adolescence. AB - Relations between academic performance and 3 aspects of social competence- socially responsible behavior, sociometric status, and self-regulatory processes (goal setting, interpersonal trust, and problem-solving styles)--were studied. Based on a sample of 423 12- and 13-year-old students, correlational findings indicate that each aspect of social competence is related significantly to students' grades. Results from multiple regression analyses suggest that when accounting for students' IQ, sex, ethnicity, school absence, and family structure, socially responsible behavior mediates almost entirely the relations between students' grades and the other 2 aspects of social competence. Socially responsible behavior and peer status appear to be related by way of their joint association with goals to be socially responsible, interpersonal trust, and problem-solving styles. Similarly, relations between socially responsible behavior and the background variables are explained by joint relations with the self-regulatory processes. The social nature of learning and the role of self regulation in both interpersonal and behavioral aspects of social competence are discussed. PMID- 1756657 TI - Functional measurement assessment of young children's ability to predict future behavior. AB - The reported experiments demonstrate that young children's ability to use previous behavioral information to predict future behavior emerges on quantitative, but not dichotomous, judgment tasks. In a first experiment, kindergartners, second graders, and fourth graders made quantitative liking judgments and predictions for peers after being presented 2 pieces of behavioral information. Children of all 3 age groups used both pieces of information in their liking judgments and predictions. In a second experiment, kindergartners were presented with 2 types of tasks; one was a quantitative prediction, comparable to the task in Experiment 1, and the second were dichotomous predictions, comparable to judgment tasks typically used in other experiments. Children's predictions were significantly more consistent with the behavioral information on the quantitative task than on either of the dichotomous tasks. These results suggest that young children believe in the ability of interpersonal behavior, but have difficulty dealing with the complexity of some prediction tasks. PMID- 1756658 TI - Children's understanding of action lines and the static representation of speed of locomotion. AB - Children's understanding of the static representation of speed of locomotion was explored in 2 experiments. In Experiment 1, 20 7-year-olds and 20 9-year-olds drew pictures of 2 people walking and running at different speeds. Children then made judgments about pairs of unambiguous drawings of a person walking or running, as did a sample of 20 adults. The drawings varied according to whether action lines, background lines, or no lines were present. Children were asked to say which figure appeared to be moving faster. In Experiment 2, 20 7-year-olds, 20 9-year-olds, and 21 adults sorted ambiguous drawings of a person walking and running at different speeds. The pictures again contained action lines, background lines, or no lines. In the drawing task, children more frequently used page position and biomechanical information than action lines to represent fast and slow walking and running. In the judgment task, 7- and 9-year-olds offered equivalent judgments of action lines and background lines, whereas adults distinguished between these pictorial devices. In the sorting task, all subjects distinguished between action lines and background lines and judged that pictures containing action lines looked faster than pictures containing background lines and pictures without lines. Taken together, the results indicate that subjects' judgments were influenced by the form of locomotion and degree of ambiguity in the depicted events they saw. The findings are consistent with the view that different categories of pictorial devices exist, but the effectiveness of each device is contingent upon the perceiver's experience with it and the context in which it appears. PMID- 1756659 TI - Contextual variation and memory retrieval at six months. AB - In 2 experiments we asked whether training in multiple contexts could eliminate context-dependent memory retrieval at 6 months as it does for adults. We found that 24-hour retention was disrupted when infants were trained in one context and tested in another but not when they were trained in multiple contexts prior to testing in a novel context (Experiment 1). After a long delay, however, training in multiple contexts did not facilitate memory retrieval in a novel context: An otherwise effective retrieval cue (the training mobile) did not alleviate forgetting 3 weeks later when it was presented in a novel context (Experiment 2). These findings demonstrate that multiple learning contexts can override the debilitating effects of an altered context on memory retrieval at 6 months, but only over the short term. The resistance of older memories to retrieval in novel contexts after long periods of disuse may be adaptive, insuring that potentially inappropriate or irrelevant memories will not be expressed. PMID- 1756660 TI - Infant temperament and genetics: an objective twin study of motor activity level. AB - Child temperament theories generally presume genetic contributions to behavioral differences, but empirical support is based largely on parent ratings of twins. These subjective ratings may be biased by parental exaggeration of dizygotic differences or of monozygotic similarities. An objective assessment of the genetic hypothesis was undertaken with motor activity level, a core dimension of most temperament theories. The activity level of 60 infant twin pairs was measured both by parent ratings and by motion recorders over a 2-day period. Data from the motion recorders showed evidence of genetic influences (RMZ = .76, RDZ = .56), as did parent ratings (RMZ = .82, RDZ = .21). The motion recorder results confirm with instrumentation a critical assumption of temperament theories and identify the presence of genetic contributors to temperamentally relevant behavioral differences in infancy. PMID- 1756661 TI - Defensive behaviors in infant rhesus monkeys: ontogeny and context-dependent selective expression. AB - We examined the ontogeny of the infant rhesus monkey's defensive behaviors and the ability to modulate them in response to specific environmental cues. Rhesus infants in 4 age groups (N = 8 per group) were briefly separated from their mothers and tested under 3 conditions: alone, in the presence of a human who averted his gaze, and in the presence of a human staring at them. Infants as young as 0 to 2 weeks displayed defensive behaviors but did not selectively respond to the human's presence or direction of gaze. By 9 to 12 weeks of age, infants modulated their responses in relation to the parameters of the threat. At this age, infant rhesus monkeys undergo cognitive and emotional changes associated with brain development similar to those in human infants 7 to 12 months old. This also is the time when human infants engage in complex emotional and behavioral responses to threatening situations. Understanding the development and expression of defensive behaviors in infant monkeys should be applicable to similar issues in emotional development of human infants. PMID- 1756662 TI - Estimation of gestational age: implications for developmental research. AB - Recent research in neonatology and obstetrics has challenged the validity of standard gestational age assessment methods. Length of gestation is a central component of research on the development of at-risk infants, yet issues concerning accuracy of this information are rarely addressed by developmental researchers. This article reviews prenatal and postnatal methods of gestational age estimation and evaluates implementation of this information in research. Recommendations concerning the assignment of gestational age in the perinatal period and the use of age correction for preterm infants are offered. PMID- 1756663 TI - Establishing the reliability and developmental validity of a neurobehavioral assessment for preterm infants: a methodological process. AB - The Neurobehavioral Assessment of the Preterm Infant was developed in 3 phases: a pilot study, an exploratory study, and a validation study. In the exploratory study, clusters characterized by conceptual cohesion and face validity were systematically subjected to statistical analyses to determine whether they also had high test-retest reliability and developmental validity. In the validation study, a shortened version of the test was used with an independent cohort of 290 preterm infants. A step-by-step methodological process was used to test whether the results from the exploratory study would generalize over cohorts, different versions of the test, different hospitals, and changes in examiners. This process yielded 7 highly stable, developmentally valid, and representative preterm neurobehavioral functions that generalized over the exploratory and the validation studies. These were: motor development and vigor, scarf sign, popliteal angle, alertness and orientation, percent asleep ratings, irritability, and vigor of crying. PMID- 1756664 TI - Infants' contribution to the achievement of joint reference. AB - This research examines whether infants actively contribute to the achievement of joint reference. One possibility is that infants tend to link a a label with whichever object they are focused on when they hear the label. If so, infants would make a mapping error when an adult labels a different object than the one occupying their focus. Alternatively, infants may be able to use a speaker's nonverbal cues (e.g., line of regard) to interpret the reference of novel labels. This ability would allow infants to avoid errors when adult labels conflict with infants' focus. 64 16-19-month-olds were taught new labels for novel toys in 2 situations. In follow-in labeling, the experimenter looked at and labeled a toy at which infants were already looking. In discrepant labeling, the experimenter looked at and labeled a different toy than the one occupying infants' focus. Infants' responses to subsequent comprehension questions revealed that they (a) successfully learned the labels introduced during follow-in labeling, and (b) displayed no tendency to make mapping errors after discrepant labeling. Thus infants of only 16 to 19 months understand that a speaker's nonverbal cues are relevant to the reference of object labels; they already can contribute to the social coordination involved in achieving joint reference. PMID- 1756665 TI - Maternal representations of attachment during pregnancy predict the organization of infant-mother attachment at one year of age. AB - While strong retrospective and concurrent associations between maternal and infant patterns of attachment have been noted, this is one of the first reports of a prospective investigation of such associations. The Adult Attachment Interview was administered to 100 mothers expecting their first child, and, at 1 year follow-up, 96 of these were seen with their infants at 12 months in the Strange Situation. Maternal representations of attachment (autonomous vs. dismissing or preoccupied) predicted subsequent infant-mother attachment patterns (secure vs. insecure) 75% of the time. These observed concordances, as well as the discordances, are discussed in terms of the uniquely powerful contribution the Adult Attachment Interview makes to the study of representational and intergenerational influences on the development of the infant-mother attachment. PMID- 1756666 TI - Emotional determinants of infant-mother attachment. AB - The present study examined the assumption that emotion-related characteristics of mothers and infants contribute to the development of infant-mother attachment in the first year of life. Mothers' emotion and personality characteristics were assessed with expressive-behavior ratings and self-report scales. Infant characteristics were measured by emotion and temperament questionnaires (mother report) and objective coding of facial expressions of emotions. Attachment classifications were determined by means of the Strange Situation procedure, and a continuous-variable index of attachment security was derived by a discriminant function procedure. Mothers' emotion experiences, expressive behaviors, and personality traits were significant predictors of the level of security of the infant-mother attachment. Infants' expressive and temperamental characteristics as rated by their mothers were also significant predictors of attachment security. PMID- 1756667 TI - Behavioral competence among mothers of infants in the first year: the mediational role of maternal self-efficacy. AB - This study tests the idea that mothers' self-efficacy beliefs mediate the effects on parenting behavior of variables such as depression, perceptions of infant temperamental difficulty, and social-marital supports. Subjects were 48 clinically depressed and 38 nondepressed mothers observed in interaction with their 3-13-month-old infants (M = 7.35 months). As predicted, maternal self efficacy beliefs related significantly to maternal behavioral competence independent of the effects of other variables. When the effects of self-efficacy were controlled, parenting competence no longer related significantly to social marital supports or maternal depression. In addition, maternal self-efficacy correlated significantly with perceptions of infant difficulty after controlling for family demographic variables. These results suggest that maternal self efficacy mediates relations between maternal competence and other psychosocial variables and may play a crucial role in determining parenting behavior and infant psychosocial risk. PMID- 1756669 TI - Social interactions and peer perceptions of young physically abused children. AB - 14 3-6-year-old children with a history of physical abuse and a closely matched comparison group of 14 nonabused children, all of whom had been in day-care for more than a year, participated in this investigation. Behavior observations, teacher reports, and peer sociometric ratings were used to evaluate children's peer interactions. It was found that abused children initiated fewer positive interactions with peers and exhibited a higher proportion of negative behavior than nonabused comparison children. Peers viewed abused children as less well liked. Further, peers were less likely to reciprocate the initiations of abused children, although they approached abused children as often as they approached comparison children. Teachers viewed abused children as more behaviorally disturbed. Overall, results indicated that abused children experience disturbed social interactions outside the home environment, despite involvement in a day care setting that provides alternative peer and adult role models. PMID- 1756668 TI - Maternal work and child-care strategies in peri-urban Guatemala: nutritional effects. AB - Associations of 293 mothers' work for earnings and child-care arrangements with the anthropometric status of their children were examined in urban Guatemala. It was hypothesized that during the period of life in which growth often falters (8 through 35 months), maternal employment could be beneficial for children. Informal workers tended to be poorer, less educated, and have more undernourished children than formal workers or nonworkers. When poverty and mother's education were controlled for, no effects of maternal employment on children's anthropometric growth patterns were seen. However, the percent of the family income the mother earned was positively associated with all anthropometric indicators, controlling for confounds. Children taken care of by preteen siblings had significantly lower weight for height than those in other situations, even controlling for SES and maternal employment status. These effects were not found in a 36-48-month-old sample. PMID- 1756670 TI - Peer reputation in middle childhood as a predictor of adaptation in adolescence: a seven-year follow-up. AB - This investigation examines the predictive significance of peer reputation in elementary school for the quality of adaptation in adolescence. A normative sample (N = 207) of third to sixth graders was administered the Revised Class Play (RCP). Each received 3 scores (Sociability-Leadership, Aggression Disruption, and Sensitivity-Isolation). 7 years later, 88% of these children and their parents participated in a questionnaire follow-up study utilizing a broad range of adolescent outcome measures (e.g., social and athletic competence, academic performance, behavioral symptoms, well-being). The 3 RCP scores were significantly related to both adolescent competence and psychopathology, supporting the predictive validity of the RCP as well as the continuity of general adaptation. Each dimension of peer reputation had a different pattern of prediction depending on the outcome criteria under consideration, suggesting the importance of a multidimensional approach to peer reputation. Positive peer reputation proved to be an important predictor of later adjustment. Sex differences were examined; results suggested somewhat different patterns of prediction for boys and girls, especially for the sensitive-isolated dimension. PMID- 1756671 TI - Multicentric osteosarcoma. Report of 5 cases. AB - Multiple foci of osteosarcoma are found in several pathological conditions: skip metastases, late bone metastases from osteosarcoma, so called metachronous osteosarcoma and multicentric osteosarcoma. The authors describe five cases with multicentric osteosarcoma of the skeleton. These lesions differ from classic osteosarcoma for their clinical and radiographical features. They generally arise in younger patients and are always sclerotic on X-rays and histological evaluation. Our data, as reported in literature, underline the poor prognosis of this disease. PMID- 1756672 TI - Circumferential fusion of the lumbar and lumbosacral spine. Comparison of two techniques of anterior spinal fusion. AB - Thirty-two patients with therapy-resistant low-back pain and justified indication for fusion were divided into two groups: 16 patients were treated with anterior fusion of the lumbosacral spine, with insertion of tricortical bone grafts of the iliac crest, and 16 patients with insertion of a fibular peg. Additional dorsal fusion of the same segments was performed. Comparison of the two techniques of circumferential fusion of the lumbosacral joint reveals comparable clinical results. A marked difference in roentgenographical criteria such as disk height, retrolisthesis, and anterior osteophytes in the adjacent segment between the two techniques was noted at the time of follow-up evaluation after 89 months and motivated the authors to abandon the fibular-peg technique. PMID- 1756673 TI - Antibiotic and antithromboembolic prophylaxis in prosthetic surgery of the knee. AB - The prevention of deep sepsis and venous thromboembolism in knee replacement surgery is of great importance for the final success of treatment. General rules of prevention must be followed when using antimicrobial drugs (environment, surgical method, patient selection). Although it does have some negative aspects (overuse, high costs, development of resistant bacteria) the administration of antibiotics is recommended, but only when it is timely, correct, and carried out for a suitable amount of time. The prevention of thromboembolism is based first on the selection of patients who risk the occurrence of angiology-related diseases, on continuous passive postoperative movement, and, finally, on intentional normovolemic hemodilution, for which the procedures used and the advantages obtained are described. PMID- 1756674 TI - The locked intramedullary Grosse Kempf nail in the treatment of proximal diaphyseal fractures of the femur. AB - The authors studied the effectiveness of locked intramedullary nailing (Grosse Kempf) in the treatment of proximal shaft femoral fractures. They reviewed 24 cases with an average two-year follow-up and which had obtained positive clinical radiographic results in 80% of cases as compared to 88% in a previous revision of femoral shaft fractures. The difference is due to the greater difficulty encountered in intraoperative reduction of fractures from which defects in axial (varus) and rotatory (extra) alignment arise. They discuss indications as regards locking type, weight-bearing, as well as surgical techniques, which may prevent some of the most frequent problems observed. PMID- 1756675 TI - The Lefevre ulnar nail. AB - The Lefevre nail applies the principles of locked intramedullary nailing in the treatment of fractures of the ulna. It is made up of two segments which slide telescopically, so that assembly may be in compression, distraction or neutral. Fixation at the two ends of the ulna is guaranteed by two transverse screws. It may be used in pseudarthrosis and osteotomies for lengthening and shortening, as well as in simple or complex fractures. The cases presented provide an overview of the use of the nail at the Brest Center, where the nail was invented and developed, and at the Rizzoli Institute. The study includes 22 fractures, 1 pseudarthrosis and 1 osteotomy. Consolidation was obtained in all of the cases after an average of 2.5 months. Immobilization in plaster was required only in cases with associated lesion of radius. The functional results obtained were satisfactory. PMID- 1756676 TI - An evaluation of some leukocytary phenotypes in subjects with evolutive primary coxarthrosis and in subjects with hip prostheses. AB - The authors examined 52 patients (36 females and 16 males) of whom 15 affected with evolutive primary coxarthrosis, 27 with hip prostheses for 4 to 13 years, and 10 with a prosthetic implant which was not tolerated. A method of indirect immunofluorescence with monoclonal antibodies against specific antigens of the cellular surface was used to typify the T-lymphocytic subpopulations (T helper/inducer and T-suppressor/cytotoxic), the activated mononucleate cells (DR+), and the B-lymphocytes and monocytes. A good correlation between the imbalances in the T-lymphocytic subpopulations, an increase in the activated mononucleate cells (principally due to T-lymphocytes) and the tolerance of the implant were observed. Based on the results obtained, the authors hypothesize the possibility of using the typing of T-lymphocytes and activated mononucleate cells, together with other biohumoral parameters, as indicators of periprosthetic tissue phologosis. PMID- 1756677 TI - Powdered alumina implants in the experimental animal: a histological study conducted in the rat. AB - The authors present a histological study conducted in the rat after powdered alumina implantation in the subcutis, the muscle and the peritoneum. After two weeks the same intense acute inflammatory reaction was observed in all of the implantation sites. After eight weeks the inflammatory reaction had regressed: there was a thin layer of connective tissue around the implant, completely isolating it from the surrounding tissues. PMID- 1756678 TI - Fracture of the posterior arch of the atlas. AB - The authors analyzed the results obtained in 10 fractures of the posterior arch of the atlas treated nonsurgically. There was consolidation in all of the cases at the end of treatment. According to the authors the element which most characterizes this fracture is constituted by its radiological diagnosis which principally makes use of lateral projection. In particular cases, when patients are characterized by multiple trauma, the fracture may go unrecognized. PMID- 1756679 TI - Os odontoideum. AB - Between January 1981 and December 1985 at the Rizzoli Orthopaedic Institute 8 patients affected with atlo-axial instability secondary to os odontoideum were submitted to surgery: all of the patients were characterized by persistent cervical pain and neurological deficit, which was still at an initial stage in 5 cases, and more severe in the remaining 3 (severe spastic tetraparesis). All of the patients were submitted to a similar treatment protocol in three stages: 1) preoperative reduction in halo-plaster, 2) surgical stabilization of C1-C2 by posterior vertebral fusion (limited to C1-C2 in 6 cases and extended as far as the occiput in the remaining 2), 3) postoperative immobilization in halo-plaster for an average of 12 weeks. At follow-up obtained after an average of 4 years and 2 months there was consolidation of the fusion in all of the cases treated: in 1 case, however, revision of the fusion was required 3 and 1/2 months after surgery, whereupon fusion was finally obtained. The total regression of pain was obtained in all 8 of the cases treated and there was evident neurological recovery in the 3 patients who had been characterized by severe spastic tetraparesis prior to surgery. The treatment protocol used in this series of patients proved to be a reliable one. Thus, it was possible to avoid the onset of chronic atlo-axial instability and its severe neurological sequelae in those cases where neurological deficit was still at an initial stage; furthermore, effective recovery was obtained in patients in whom neurological deficit was severe. PMID- 1756680 TI - Seckel's syndrome: presentation of one case associated with Legg-Calve-Perthes disease. AB - The authors present the case of one patient affected with Seckel's syndrome which came to their observation as a result of pain in the hip with limping, diagnosed after Legg-Calve-Perthes disease. There seems to be an accidental relationship between the two diseases, although Legg-Calve-Perthes disease is frequently described in all cases of endocrinous dwarfism. PMID- 1756681 TI - Serum ketone response to glucagon as a marker of insulin dependency in diabetics. AB - The serum ketone response to glucagon was measured in 10 patients with IDDM and 37 with NIDDM. In both groups, serum 3-hydroxybutyrate increased significantly after intravenous injection of 1 mg glucagon. The difference between the serum level of 3-hydroxybutyrate at 30 min and basal level [delta 3-OHBA(30')] was 133 +/- 25 mumol/l in the patients with IDDM, 13 +/- 8 mumol/l in those with NIDDM treated by diet alone or with oral hypoglycemic agents and 23 +/- 13 mumol/l in those with NIDDM treated with insulin. The delta 3-OHBA(30') was significantly greater in IDDM patients than in both groups of NIDDM patients (P less than 0.001). The delta 3-OHBA(30') was greater than 87 mumol/l in eighty percent of IDDM patients, but smaller than 87 mumol/l in both groups of NIDDM patients. The delta 3-OHBA(30') was correlated with the difference between the plasma level of C-peptide at 6 min and basal level [delta CPR(6')] (r = -0.540, P less than 0.001). The delta 3-OHBA(30') was not correlated with fasting plasma levels of glucose, fructosamine or hemoglobin A1c. These observations show that measurement of the serum ketone response to glucagon is a useful marker of insulin dependency. In order to determine insulin dependency, the simultaneous measurement of concentrations of ketones and C-peptide is indicated during the glucagon stimulation test. PMID- 1756682 TI - Sarimner: a computer model of diabetes physiology for education of physicians and patients. AB - Often diabetic patients have developed their skills by some trial-and-error-like training over a long period of time. To minimize this inconvenience we have made a mathematical model to facilitate diabetes education. The model consists of a number of blocks involved in diabetes physiology: digestion, blood (transport), pancreas, injected insulin absorption, liver, muscles, kidneys, metabolism and insulin sensitivity. The model serves as a demonstration object and the user can change meals, exercise and injections and see the resulting blood glucose level. A more experienced user can search for further explanations of different phenomena deeper in the physiology of the model. The model does not solve any problem for the user, but creates a learning situation in which the user, led by his own curiosity, successively increases his experience of diabetes physiology. Sarimner is implemented as an easy-to-use menu driven computer program for IBM PC clones with Hercules, EGA or VGA graphics. PMID- 1756683 TI - Postprandial glucose and insulin responses to various tropical fruits of equivalent carbohydrate content in non-insulin-dependent diabetes mellitus. AB - The plasma glucose and insulin responses were determined in 10 NIDDM female patients following the ingestion of tropical fruit containing 25 g of carbohydrate. The five tropical fruits were pineapple, mango, banana, durian and rambutan. Blood was drawn at 0, 30, 60, 120 and 180 min, respectively. The results showed that the glucose-response curves to mango and banana were significantly less than those to rambutan, durian and pineapple (P less than 0.05). Only the glucose area after mango ingestion was significantly less than the glucose areas of the other fruits (P less than 0.05). The insulin response curve and insulin area after durian ingestion was statistically greater than after ingestion of the others. We concluded that after mango ingestion, the glucose area was lower than it had been after rambutan, durian and pineapple ingestion and the insulin area was lower than that after durian ingestion of equivalent carbohydrate content in type 2 (NIDDM) diabetes. PMID- 1756684 TI - High prevalence of undiagnosed diabetes among Chinese patients with ischaemic stroke. AB - We reviewed the prevalence of diabetes mellitus, hypertension and cigarette smoking in 176 Chinese patients with acute stroke, classified, on computed tomographic findings, as intracerebral haemorrhage or cerebral infarction. In all patients with no known history of diabetes, a 75 g OGTT was done 3-6 months after ictus and interpreted using WHO criteria. The overall prevalence of diabetes and impaired glucose tolerance (IGT) was 33.5% and 21.0%, respectively, with a higher prevalence being found in patients with cerebral infarction (P less than 0.05). Forty percent of those with diabetes were previously undiagnosed - all but 2 had ischaemic stroke. Compared to reported findings in the general population, an increased prevalence of hypertension, and possibly also cigarette smoking was found in patients with both stroke categories. On the other hand, significant hypercholesterolaemia was not found in patients of either category. In view of the high prevalence of undiagnosed diabetes among these stroke patients and the increased morbidity and mortality associated with diabetes mellitus, screening for diabetes is recommended especially in those with ischaemic stroke. If a fasting plasma glucose of greater than or equal to 6 mmol/l was used for the initial screening of undiagnosed diabetes in this group of patients, the sensitivity and specificity values would have been 78% and 94%, respectively. Whether this cut-off value can be cost-effectively employed for mass screening remains to be confirmed by studies involving larger numbers of stroke patients. PMID- 1756685 TI - Hypoglycemia associated hospitalizations in a population with a high prevalence of non-insulin-dependent diabetes mellitus. AB - In order to evaluate the rates, causes, and clinical features of hospitalizations associated with hypoglycemia in a population with a high prevalence of non insulin-dependent diabetes mellitus (NIDDM), a retrospective analysis of medical records was conducted in a multi-hospital primary care system on the Navajo Indian Reservation. During an estimated 26,125 person-years of observation among diabetic patients, there were 126 hypoglycemia-associated admissions related to diabetes among 109 diabetic patients, yielding a hospitalization rate of 4.7 per 1000 person-years (95% CI 4.1-5.7). Using estimates of drug utilization based on a defined daily dose, hospitalization rates were 5.8 per 1000 PY (95% CI 4.4-7.6) for chlorpropamide, 16.0 per 1000 PY (95% CI 9.5-26.9) for glyburide, and 9.1 per 1000 PY (95% CI 6.9-11.9) for insulin. After stratification by age, the relative risk for hypoglycemia-associated hospitalization among patients prescribed glyburide compared to those prescribed chlorpropamide was 2.8 (95% CI 1.6-4.9). Hypoglycemia-associated hospitalizations were relatively common among patients with NIDDM, particularly among those treated with glyburide. PMID- 1756686 TI - Contribution of hyperglycemia and renal damage to urinary C-peptide clearance in non-insulin-dependent diabetic patients. AB - The variation of urinary C-peptide clearance in relation to hyperglycemia and renal damage was evaluated in 57 patients with non-insulin-dependent diabetes mellitus (NIDDM) with and without overt proteinuria, 14 nondiabetic patients with renal disease (RD) and 18 healthy control subjects. Urinary C-peptide clearance expressed as the ratio of urinary C-peptide to creatinine clearance (CCP/CCR) in the fasting state did not differ in control subjects and RD patients, and was higher equally in NIDDM patients with and without proteinuria. In NIDDM patients without overt proteinuria, urinary levels of C-peptide, beta 2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin as well as CCP/CCR ratio all decreased significantly with short-term glycemic control (P less than 0.05). Despite a wide range of CCP/CCR ratio (0.07-0.73), a weak but significant correlation (r = 0.56, P less than 0.005) was found between fasting serum and urinary C-peptide levels in NIDDM patients. These results suggest that urinary C peptide may easily be affected by hyperglycemia per se rather than renal damage, while urinary B2M, NAG and albumin may be affected by both hyperglycemia and renal damage. When the urinary C-peptide level is interpreted, the influence of hyperglycemia on it must be taken into consideration. PMID- 1756687 TI - Plasma urate in diabetes: relationship to glycaemia, glucose disposal, microvascular complications and the variations following oral glucose. AB - In order to provide further insights into the conflicting reports of associations between diabetes and uric acid metabolism, we studied 175 adult diabetic patients (56 IDDM, 119 NIDDM) and 114 matched control subjects. Plasma uric acid (PUA) concentrations were not significantly different between diabetic and control subjects, despite increased urinary urate in diabetic patients. There were no significant associations, in diabetic patients, between PUA and (i) type of diabetes, (ii) glycaemic control, (iii) retinopathy and (iv) proteinuria. Plasma urate did not correlate with the KG constant for glucose disposal rate during IVGTT, thus indicating that PUA may not be related to insulin action. In a separate study, PUA rose sharply, peaking at 30 min, and fell subsequently in both newly diagnosed NIDDM patients (n = 20) and subjects with impaired glucose tolerance (n = 15) in response to standard OGTT, in contrast to normal controls (n = 35) in whom PUA rose gradually to a peak at 120 min. Mean rise in PUA from baseline to peak was significant (P less than 0.05) in the diabetic group only. These differences in PUA response during an OGTT between subjects with abnormal glucose metabolism and normal controls may be a feature in the metabolic evolution of diabetes and need further investigation. PMID- 1756688 TI - Treatment of lower respiratory infections in outpatients with ofloxacin compared with erythromycin. AB - To assess the safety and efficacy of a ten-day oral course of ofloxacin (400 mg 12 hourly) as compared with erythromycin (400 mg every 6 hours) for treatment of lower respiratory tract infections, fifty-two adult outpatients with pulmonary infiltrates (pneumonia) or with a cough and purulent sputum (bronchitis) were evaluated. Expectorated sputum specimens were Gram-stained and cultured, and antibody titres to Mycoplasma pneumoniae, Legionella pneumophilia, and in most cases Chlamydia pneumoniae were measured on acute and convalescent serum samples. Patients were evaluated clinically, microbiologically and radiographically three to five days after concluding therapy; the incidence of adverse reactions was monitored throughout the study period. The ofloxacin group (N = 25) was comprised of nineteen patients with pneumonia and six patients with bronchitis. The erythromycin group (N = 27) was comprised of thirteen patients with pneumonia and fourteen patients with bronchitis. All fifty-two patients were either clinically improved or cured after therapy. Microbiological cure was documented in all fourteen cases (27%) in which causative pathogens were identified. Clinical cure was achieved with ofloxacin in 68% of patients with pneumonia and in 83% of patients with bronchitis, while clinical cure with erythromycin was achieved in 46% of patients with pneumonia and 54% of patients with bronchitis. Adverse reactions (mostly mild gastrointestinal or central nervous system symptoms) were reported by eight patients receiving ofloxacin and four patients receiving erythromycin. While the types of adverse effects were similar, ofloxacin showed a trend toward a higher rate of cure than erythromycin. Ofloxacin is a promising new antibiotic for the treatment of acute lower respiratory infections. PMID- 1756689 TI - Analgesia by nefopam: does it act through serotonin? AB - In an attempt to clarify the possible mode of action of nefopam, a new analgesic compound, the authors tested its effects on imipramine (IMI) binding to platelet membranes. The results showed that nefopam exerted a concentration-dependent inhibition of IMI binding, with a potency comparable to that of tricyclic antidepressants. This finding suggests a possible intervention of serotonergic mechanisms in nefopam-related analgesia. PMID- 1756690 TI - Evaluation of phenytoin in rheumatoid arthritis--an open study. AB - In an open study, thirty-five patients with active rheumatoid arthritis were treated with phenytoin. Various clinical and laboratory parameters showed good improvement after phenytoin. Early morning stiffness was significantly reduced after 8 weeks (p less than 0.05); pain index (p less than 0.001), articular index (p less than 0.01) and grip strength (p less than 0.01) showed significant improvement after 24 weeks. There was significant reduction in erythrocyte sedimentation rate (p less than 0.01). Except for three patients (skin rash in one and gastric irritation in two), all others tolerated phenytoin well. The results of the present study support the usefulness of phenytoin as a disease modifying drug for rheumatoid arthritis. PMID- 1756691 TI - New carnitine derivatives for the therapy of cutaneous ulcers in vasculopathics. AB - The treatment of arterial and venous cutaneous ulcers in vasculopathic patients is a difficult task, since it requires the prolonged administration of drugs which are often unable to correct the various pathogenetic factors, including rheological disorders, responsible for the lesions. The authors, basing themselves upon recent studies demonstrating the rheological and vasoactive as well as metabolic activities of propionyl l-carnitine, have decided to examine this substance for the treatment of arterial and venous cutaneous ulcers of the lower extremities. Propionyl l-carnitine administered orally or intravenously to eighteen vasculopathics with cutaneous ulcers was responsible for the complete or nearly complete regression of trophic lesions in 78.9% of the patients. Therapeutic failure or only modest results were observed in four patients. In addition a highly significant increase in flow velocity was observed in arteriopathic patients. It is particularly important to note that these clinical results were obtained in patients refractory to all other forms of therapy. PMID- 1756692 TI - [Changes in the blood and plasma volumes during diagnostic angiocardiography. Differences between high- and low-osmolality contrast media]. AB - Changes in blood and plasma volumes were investigated in the course of diagnostic cardiac catheterizations, comparing the effect of a high and a low osmolar contrast medium in 30 patients (5 women and 25 men; mean age 53 [19-76] years) with coronary heart disease (n = 27) or valvular defect (n = 3). Using a randomized, double-blind protocol 15 patients received amidotrizoic acid (2.1 osmol/kg; mean dosage 166 +/- 68 or 2.2 +/- 1.1 ml/kg), while 15 patients received iopamidol (0.8 osmol/kg; mean dosage 154 +/- 78 ml or 2.1 +/- 1.0 ml/kg). The indocyanine-green method and the haematocrit were used to measure blood and plasma volumes immediately before and after the angiocardiography. Blood volume after amidotrizoic acid injection increased by a mean of 4.9% (228 +/- 242 ml) and by 0.4% (17 +/- 197 ml) after iopamidol (P less than 0.05). Plasma volume increased by a mean of 11.8% (331 +/- 150 ml) after amidotrizoic acid and 5.7% (157 +/- 97 ml) after iopamidol (P less than 0.01). The increase in plasma volume correlated with the dose of contrast medium: 2 ml per ml amidotrizoic acid (r = 0.93) and 1 ml per ml iopamidol (r = 0.82).--During angiocardiography blood and plasma volume may increase by up to 500 ml, an increase which depends not only on dosage but also on the osmolality of the injected contrast medium. PMID- 1756693 TI - [Percutaneous sonographically guided fine-needle puncture and drainage of pyogenic abscesses]. AB - Between January 1988 and April 1991, a total of 79 ultrasound-directed percutaneous punctures and (or) drainage of abscesses were performed on 31 patients (15 men, 16 women; mean age 63 [31-85] years). There were 14 hepatic, 4 splenic, 4 abdominal wall and 3 pancreatic abscesses, and one each subphrenic, presacral, retrocaecal, ischiorectal, pulmonary and in the psoas. After ultrasound localization of the abscess a fine-needle puncture was performed, after which the abscess cavity was emptied as much as possible or, in abscesses larger than 5 cm in diameter, drained through a pig-tail catheter (6-8, 4 F). Several punctures were needed in 16 patients, while in 15 a percutaneous drainage over 2-8 days was necessary. Treatment was successful after 4-17 days in 25 patients. One patient died in septic shock. Operative intervention after diagnostic puncture was undertaken in 5 patients. There were no complications related to the method. In 11 patients the further course was determined by an underlying malignant disease. No recurrence has been noted (4-36 months after treatment) in 14 patients with a benign underlying disease. Percutaneous puncture and drainage of pyogenic abscesses is a technically simple method which achieves good results. PMID- 1756694 TI - [The morphology and clinical picture of epithelioid hemangioendothelioma of the lung]. AB - A 36-year-old woman presented with multiple shadows, up to 1 cm in diameter, in both lungs revealed by routine chest radiography. Right thoracotomy showed numerous firm nodules in the middle and lower lobes. Histological examination of the wedge biopsy disclosed an epithelioid haemangioendothelioma of the lung (positive immunohistochemical reaction for factor VIII-associated antigen). Eight years later the patient remains symptom-free without treatment and the radiological picture is almost unaltered. Another woman, 22 years old, had a skin nodule near the right external malleolus. It was removed and found to be a semi malignant haemangioendothelioma. Five years later a chest radiograph showed finely nodular shadowing in both lungs which roused suspicion of sarcoidosis. She had steroid therapy for one year, but the radiological findings remained unchanged. After a further 10 years a round lesion, some 3 cm in diameter with partial calcification, was found in the right lower lobe. Histological examination revealed an epithelioid haemangioendothelioma with a positive immunohistochemical reaction for factor VIII-associated antigen. She subsequently complained of severe pain in the left shoulder (with histologically demonstrated bone involvement by the neoplasm) together with rapidly increasing dyspnoea. Seventeen years after the original diagnosis she died of rapidly progressive diffuse lymphangiomatosis carcinomatosa. Post mortem secondary deposits were found in the liver as well. PMID- 1756695 TI - [Cryptococcal meningitis in AIDS: successful long-term prophylaxis with fluconazole]. AB - A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding. Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus. Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis. Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily. The clinical, microbiological and serological findings regressed after 4 weeks. After 8 weeks the creatinine concentration rose to 2.5 mg/dl. Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g. He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily. The cryptococcal antigen titre had fallen to normal within one year. The prophylactic regimen has been continued now for three years without recurrence or other fungal infection. PMID- 1756696 TI - [Endoscopic Doppler sonography]. PMID- 1756697 TI - [From fatal hemorrhagic diathesis to life-threatening thrombosis risk. New complications of a "gentle" treatment of acute promyelocytic leukemias with all trans-retinoic acid]. PMID- 1756698 TI - [Friedrich Daniel von Recklinghausen. A reminiscence on the occasion of the centenary of his publication Osteitis fibrosa or deformans, osteomalacia and osteoplastic carcinosis in their interrelationships]. PMID- 1756699 TI - [Pneumothorax in AIDS]. PMID- 1756700 TI - Control of infections. PMID- 1756701 TI - Bacteriology of infections in a rural tropical area of Kenya: isolates and antibiotic susceptibility. AB - No microbial data are available for rural tropical areas. Yet most people in Africa live in rural areas where the burdens of infectious diseases remain the primary cause for morbidity and mortality. A pilot study was done by culturing midstream urine from patient with dysuria (100 with Gram-negative fermentative rods), blood from patients with FUO (55/307 positive) and swabs from patients with infected wounds (29 with Staphylococcus aureus). Bacteria were identified and susceptibility tests were performed according to protocols. Klebsiella was the most common isolate from urine (48%). The overall resistance in urine isolates for ampicillin was 76% and for cotrimoxazole, 60%. The main isolates from blood were Klebsiella Enterobacter sp (21/55) and Salmonella (14/55) in patients from agricultural areas, and Staphylococcus aureus (12/55) in patients from desert areas. The Staphylococcus aureus from wounds were all penicillin resistant and 9/29 were cloxacillin resistant. Influence of the environment, underlying pathology and previous use of antibiotics give unexpected predominance of Klebsiella and high resistance in all isolates. Large scale surveillance studies are needed so that prescription of antibiotics can be based on locally obtained data. PMID- 1756702 TI - Occurrence of toxic shock syndrome toxin-1 producing Staphylococcus aureus and the anti TSST-1 serostatus of hospital personnel in Nigeria. AB - Of the 56 S. aureus strains tested, five (8.9%) isolates (four from asymptomatic nasal carriage and one from a non TSS staphylococcal disease) demonstrated TSST-1 production in vitro. Among the toxin positive strains the clinical isolate belonged to phage group I, 29/52 and the nasal carriage isolates were either non typable or ungroupable. Eighty-nine percent of isolates including all TSST-1 positive strains showed binding to crystal violet and were traced to S. aureus var. hominis (CV type C/D). A. aureus var. bovis (CV type A/B) were found only in nasal carriage group (10.7%) and did not bind crystal violet. During the sero surveillance 101 out of 220 hospital personnel (48.1%) showed TSST-1 antibodies of IgG class at 1:1000 sera dilution. The four individuals with asymptomatic nasal carriage of TSST-1 positive staphylococci showed no antibody to the toxin. Anti TSST-1 levels persisted in 58 (57.4%) and 10 (9.9%) individuals at higher sera dilutions of 10(-4) and 10(-5) respectively. PMID- 1756703 TI - Seroepidemiological study for HBV markers and anti-delta in Kenya. AB - An HBV carrier rate of 3.0% in outpatients and 1.4% in school children, was found in a sero-epidemiological survey in Muranga District, Kenya. The prevalence of anti-Delta in HBV carriers was 42%. The prevalence of HBV carriers and HBV marker positive cases was high in family members of HBV carriers. The yearly attack ratio of HBV was low in primary school children, non-carrier family members and even carrier family members. Mother to baby vertical transmission was very high when mothers were HBeAg positive HBV carriers. Such vertical transmission may now be of major importance. PMID- 1756704 TI - Prevalence of psychiatric illness among Kenyan children. PMID- 1756705 TI - Hypertension in Kitui district: a comparative study between urban and rural populations. AB - This study was conducted in 1986, with the objective of finding out whether high blood pressure is a problem in the urban and rural populations of Kitui, and the risk factors that may be contributing to the problem. 360 people were visited at home and work places and their blood pressure, were taken in the sitting position under field conditions. A questionnaire on age, sex, marital status, occupation, smoking, miraa chewing and alcohol consumption and the number of people in the household was administered to every study subject, after which their heights and weights were recorded. Prevalence was found to be 6.4%. There was no difference in the occurrence of hypertension between the urban and rural populations. The relationship between the occurrence of hypertension and other parameters is presented and discussed in this paper. PMID- 1756706 TI - Foetal and maternal outcome of vacuum extraction. AB - In a prospective study, 167 vacuum extractions (VE) performed at the Kenyatta National Hospital, Nairobi, formed 6.3% of the total deliveries. Most patients were young and of low parity. There were no maternal deaths. The overall maternal morbidity rate was 22% and were mostly minor. Post partum haemorrhage was the most common maternal complication. There were 5 failed VEs. Perinatal morbidity and mortality rates were 16.2% and 4.8% respectively. Intrauterine asphyxia was the commonest cause of death. Several complications could have been avoided by more stringent use of the instrument. The place of VE in a busy obstetric unit is discussed. PMID- 1756707 TI - The dynamics of medical students career and medical specialty choices, and their implication for medical education in developing countries: a Maiduguri Medical School study. AB - This is a cross-section study based on questionnaire of the students in all the three clinical years of the medical school at the University of Maiduguri, Nigeria. The aim of the study was to explore the dynamics of career and medical specialisation decision and inclinations of the students with the view to seeing how they match the need of medical services in the country, and hence to discover those areas and methods which may be useful in this connection. The study shows that previous (including pre-medical school) exposures to the chosen specialties and ongoing medical school exposures and role models are the most important factors in specialty choices while job opportunities and local trends are important in the career decisions. It is therefore proposed that since medical exposures and role models can be influenced in the medical curriculum, it would be necessary to do this in the specialties of general medical practice (Family Medicine, Primary Medical Care) and the Community Medicine which are vital in the containment of the communicable and poverty/social inequality disease problems of this and other developing countries. PMID- 1756708 TI - Occurrence of Plesiomonas shigelloides--associated diarrhoea in Calabar, Nigeria. AB - The prevalence, clinical profiles and virulence factors of Plesiomonas shigelloides were determined in patients attending the University of Calabar Teaching Hospital, Microbiology Laboratory. P. shigelloides was isolated from 12 (1.4%) of 880 patients with diarrhoea and from none of the controls (P less than 0.05). Isolates were mostly from febrile children less than or equal to 10 years with most of the infections occurring during the rainy months. Although our findings suggest the significance of Plesiomonas in acute diarrhoea in this environment, our isolates did not seem to show any of the proxy indicators of virulence usually associated with other enteric pathogens. PMID- 1756709 TI - Nutritional requirements in chronic renal failure and end stage renal disease at the Kenyatta National Hospital. AB - Since August, 1984 renal replacement therapy with haemodialysis, peritoneal dialysis and renal transplant has been carried out regularly at the renal unit of the Kenyatta National Hospital (KNH). Various nutritional disturbances have been met. Nausea, vomiting and anorexia have been noticed frequently particularly in those on intermittent peritoneal dialysis (IPD). The same problems were experienced in those few patients who were on continuous ambulatory peritoneal dialysis (CAPD). The patients were usually malnourished, the malnutrition being of protein-calorie type. At the start of the programme of renal replacement therapy in 1984, the problems of poor nutrition were worse but are currently improving. At the moment our patients with chronic renal failure (CRF) and end stage renal disease (ESRD) on dialysis are scattered all over the medical and paediatric wards at KNH. This has impeded the smooth surveillance of patients' diets by the few available nutritionists. The review of our performance from 1984 1988 on the nutritional status of patients with CRF and ESRD is an attempt to create a normal dietary cover for patients with the above problems. PMID- 1756710 TI - Pemphigus vulgaris: case report in a Nigerian Negro. AB - A middle-aged Nigerian male had generalised pruritus, widespread flaccid vesicles and bullae, with ulcerations of the skin that heal without scarring, weight loss, positive nikolsy sign, anaemia, and marked eosinophilia. Pemphigus vulgaris is a rare disease among those of Negroid extraction, we therefore, report this case involving a Nigerian. PMID- 1756711 TI - Pseudo-precocious puberty in a Kenyan African child: a case report. AB - A female Kenyan child with pseudoprecocious puberty due to juvenile granulosa cell tumour is presented. Clinical features in this patient included a mass in the lower abdomen, a growth spurt and appearance of pubic hairs as well as enlargements of the breasts. No similar case has been reported in a Kenyan child. The management and review of literature are discussed. PMID- 1756712 TI - T-DNA gene 5 of Agrobacterium modulates auxin response by autoregulated synthesis of a growth hormone antagonist in plants. AB - Oncogenes carried by the transferred DNA (T-DNA) of Agrobacterium Ti plasmids encode the synthesis of plant growth factors, auxin and cytokinin, and induce tumour development in plants. Other T-DNA genes regulate the tumorous growth in ways that are not yet understood. To determine the function of T-DNA gene 5, its coding region was expressed in Escherichia coli. Synthesis of the gene 5 encoded protein (26 kDa) correlated with a 28-fold increase in conversion of tryptophan to indole-3-lactate (ILA), an auxin analogue. Expression of chimeric gene 5 constructs in transgenic tobacco resulted in overproduction of ILA that enhanced shoot formation in undifferentiated tissues and increased the tolerance of germinating seedlings to the inhibitory effect of externally supplied auxin. Promoter analysis of gene 5 in plants revealed that its expression was inducible by auxin and confined to the vascular phloem cells. cis-regulatory elements required for auxin regulation and phloem specific expression of gene 5 were mapped to a 90 bp promoter region that carried DNA sequence motifs common to several auxin induced plant promoters, as well as a binding site for a nuclear factor, Ax-1. ILA was found to inhibit the auxin induction of the gene 5 promoter and to compete with indole-3-acetic acid (IAA) for in vitro binding to purified cellular auxin binding proteins. It is suggested therefore that ILA autoregulates its own synthesis and thereby modulates a number of auxin responses in plants. PMID- 1756713 TI - The surface-exposed tyrosine residue Tyr83 of pea plastocyanin is involved in both binding and electron transfer reactions with cytochrome f. AB - Site-directed mutants of the pea plastocyanin gene in which the codon for the surface-exposed Tyr83 has been changed to codons for Phe83 and Leu83 have been expressed in transgenic tobacco plants. The mutant proteins have been purified to homogeneity and their conformations shown not to differ significantly from the wild-type plastocyanin by 1H-NMR and CD. Overall rate constants for electron transfer (k2) from cytochrome f to plastocyanin have been measured by stopped flow spectrophotometry and rate constants for binding (ka) and association constants (KA) have been measured from the enhanced Soret absorption of cytochrome f on binding plastocyanin. These measurements allow the calculation of the intrinsic rate of electron transfer in the binary complex. An 8-fold decrease in the overall rate of electron transfer to the Phe83 mutant is due entirely to a decreased association constant for cytochrome f, whereas the 40-fold decrease in the overall rate of electron transfer to the Leu83 mutant is due to weaker binding and a lower intrinsic rate of electron transfer. This indicates that Tyr83 is involved in binding to cytochrome f and forms part of the main route of electron transfer. PMID- 1756714 TI - A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. AB - Mutational analysis of p21ras has shown that plasma membrane targeting requires the combination of a CAAX motif with a polybasic domain of six lysine residues or a nearby palmitoylation site. However, it is not known from these studies whether these signals alone target p21ras to the plasma membrane. We now show that these C-terminal sequences are sufficient to target a heterologous cytosolic protein to the plasma membrane. Interestingly, the key feature of the p21K-ras(B) polybasic domain appears to be a positive charge, since a polyarginine domain can function as a plasma membrane targeting motif in conjunction with the CAAX box and p21K ras(B) with the polylysine domain replaced by arginines is biologically active. Since some ras-related proteins are modified by geranylgeranyl rather than farnesyl we have investigated whether modification of p21ras with geranylgeranyl affects its subcellular localization. Geranylgeranyl can substitute for farnesyl in combining with a polybasic domain to target p21K-ras(B) to the plasma membrane, but such geranylgeranylated proteins are more tightly bound to the membrane. This increased avidity of binding is presumably due to the extra length of the geranylgeranyl alkyl chain. PMID- 1756715 TI - A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. AB - The lysosomal disorder galactosialidosis is caused by deficiency of the protective protein in the absence of which the activities of the enzymes beta galactosidase and neuraminidase are reduced. Aside from its protective function towards the two glycosidases, this protein has cathepsin A-like activity. A point mutation in the protective protein gene, resulting in the substitution of Phe412 with Val in the gene product, was identified in two unrelated patients with the late infantile form of the disease. Expression in COS-1 cells of a protective protein cDNA with the base substitution resulted in the synthesis of a mutant protein that lacks cathepsin A-like activity. The newly made mutant precursor was shown to be partially retained in the endoplasmic reticulum. Only a fraction is transported to the lysosomes where it is degraded soon after proteolytic processing into the mature two-chain form. Since the mutant precursor, contrary to the wild type protein, does not form homodimers, the dimerization process might be a condition for the proper targeting and stable conformation of the protective protein. These results clarify the mechanism underlying the combined deficiency in these patients, and give new insight into the structure-function relationship of the wild type protein. PMID- 1756716 TI - A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery. AB - The yeast VPS15 gene encodes a novel protein kinase homolog that is required for the sorting of soluble hydrolases to the yeast vacuole. In this study, we extend our previous mutational analysis of the VPS15 gene and show that alterations of specific Gps15p residues, that are highly conserved among all protein kinase molecules, result in the biological inactivation of Vps15p. Furthermore, we demonstrate here that short C-terminal deletions of Vps15p result in a temperature-conditional defect in vacuolar protein sorting. Immediately following the temperature shift, soluble vacuolar hydrolases, such as carboxypeptidase Y and proteinase A, accumulate as Golgi-modified precursors within a saturable intracellular compartment distinct from the vacuole. This vacuolar protein sorting block is efficiently reversed when mutant cells are shifted back to the permissive temperature; the accumulated precursors are rapidly processed to their mature forms indicating that they have been delivered to the vacuole. This rapid and efficient reversal suggests that the accumulated vacuolar protein precursors were present within a normal transport intermediate in the vacuolar protein sorting pathway. In addition, this protein delivery block shows specificity for soluble vacuolar enzymes as the membrane protein, alkaline phosphatase, is efficiently delivered to the vacuole at the non-permissive temperature. Interestingly, the C-terminal Vps15p truncations are not phosphorylated in vivo suggesting that the phosphorylation of Vps15p may be critical for its biological activity at elevated temperatures. The rapid onset and high degree of specificity of the vacuolar protein delivery block in these mutants suggests that the primary role of Vps15p is to regulate the sorting of soluble hydrolases to the yeast vacuolar compartment. PMID- 1756717 TI - Leishmanial protein kinases phosphorylate components of the complement system. AB - Externally oriented protein kinases are present on the plasma membrane of the human parasite, Leishmania. Since activation of complement plays an important role in the survival of these parasites, we examined the ability of protein kinases from Leishmania major to phosphorylate components of the human complement system. The leishmanial protein kinase-1 (LPK-1) isolated from promastigotes of L. major was able to phosphorylate purified human C3, C5 and C9. Only the alpha chain of C3 and C5 was phosphorylated. The beta-chain appeared not to be a substrate for this enzyme. C3b which is formed by proteolytic cleavage of C3 was not phosphorylated by LPK-1. Trypsin treatment of phosphorylated C3 (P-C3) resulted in the disappearance of 32P from the alpha-chain. This was correlated with the conversion of the C3 alpha-chain to the alpha'-chain of C3b, and the appearance of a 9 kDa 32P fragment comigrating with the C3a fragment of C3. P-C3 was more resistant to cleavage by trypsin than nonphosphorylated C3. LPK-1 phosphorylated purified C3a and two synthetic peptides, C3a21R and YA-C3a10R, derived from its COOH-terminal end, which contain the C3a binding site to leukocytes and platelets. LPK-1 did not phosphorylate C3a8R. Phosphoamino acid analysis of the synthetic peptides indicated that serine 71 of C3a was phosphorylated by LPK-1. Treatment of C3 with either methylamine or freeze-thaw C3 (H2O) prevented phosphorylation by the LPK-1 suggesting that substrate conformation may be involved in recognition by the leishmanial enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756718 TI - Saccharomyces cerevisiae a- and alpha-agglutinin: characterization of their molecular interaction. AB - An O-glycosylated protein of approximately 18 kDa responsible for mating type specific agglutination has been isolated from Saccharomyces cerevisiae a cells, purified to homogeneity and via peptide sequences the gene was cloned by PCR. An open reading frame codes for a protein of 69 amino acids. A minimum of five serine and five threonine residues of the mature protein are glycosylated. alpha Agglutinin is a highly N-glycosylated protein of approximately 250 kDa. Both purified agglutinins form a specific 1:1 complex in vitro. Pretreatment of alpha agglutinin, but not of alpha-agglutinin, with diethylpyrocarbonate (DEPC) prevents formation of the complex; treatment of alpha-agglutinin in the presence of alpha-agglutinin protects the former from DEPC inactivation. By carboxy terminal shortening of the alpha-agglutinin gene and by replacing three of its eight histidyl residues by arginine, the active region of alpha-agglutinin for interaction with alpha-agglutinin has been defined. Neither the N- nor the O linked saccharides of the two agglutinins seem to be essential for their interaction. PMID- 1756719 TI - Identification of a novel recognition sequence for the integrin alpha 4 beta 1 in the COOH-terminal heparin-binding domain of fibronectin. AB - The type III connecting segment of fibronectin contains two cell binding sites, represented by the peptides CS1 and CS5, that are recognized by the integrin receptor alpha 4 beta 1. Using assays measuring the spreading of A375-SM human melanoma cells, we now report that the adhesion promoting activity of a 29 kDa protease fragment of fibronectin containing the COOH-terminal heparin-binding domain (HepII), but lacking CS1 and CS5, is completely sensitive to anti-alpha 4 and anti-beta 1 antibodies, suggesting that HepII contains a third alpha 4 beta 1 binding sequence. Examination of the primary structure of HepII revealed a sequence with homology to CS1. A 19mer peptide spanning this region (designated H1) was found to support cell spreading to the same level as the 29 kDa fragment. H1-dependent adhesion was completely sensitive to anti-alpha 4 and anti-beta 1 antibodies. When soluble peptides were tested for their ability to block cell spreading on the 29 kDa fragment, a 13mer peptide comprising the central core of H1 was found to be completely inhibitory. The active region of H1 was localized to the pentapeptide IDAPS, which is homologous to LDVPS from the active site of CS1. Taken together, these results identify a novel peptide sequence in the HepII region of fibronectin that supports alpha 4 beta 1-dependent cell adhesion. PMID- 1756720 TI - Mutations in TrpI binding site II that differentially affect activation of the trpBA promoter of Pseudomonas aeruginosa. AB - In vitro, Pseudomonas aeruginosa TrpI protein activates transcription initiation at the trpBA promoter (trpPB) and represses initiation at its own promoter (trpPI), which diverges from, and overlaps, trpPB. Indoleglycerol phosphate (InGP) reduces the TrpI concentration required for binding to its strong binding site (site I), as measured by repression of trpPI; it also facilitates activation of trpPB, presumably because it enables TrpI to bind to a weaker binding site (site II) and thereby interact with RNA polymerase. The role of site II and InGP in regulation of the two promoters was investigated by constructing site II mutants. A 2 bp substitution affected the ability of TrpI to activate trpPB, but did not significantly affect TrpI binding to site II. A more extensive (8 bp) substitution inhibited TrpI-mediated activation of trpPB and TrpI-mediated protection of site II in a DNase I footprinting assay. However, the mutation did not alter the pattern of TrpI binding observed in gel retardation experiments. In particular, a more slowly-migrating complex (Complex 2) whose appearance was correlated with TrpI binding to site II was formed equally well on a wild-type or substituted DNA fragment. Based on the mutant phenotypes, we propose that a particular sequence of protein--protein and protein--DNA interactions is required for activation of trpPB by TrpI and InGP. PMID- 1756721 TI - Amino acids determining operator binding specificity in the helix-turn-helix motif of Tn10 Tet repressor. AB - Each of 22 amino acids in the proposed alpha-helix-turn-alpha-helix operator binding motif of the Tn10 encoded Tet repressor was replaced by alanine and one residue was replaced by valine to determine their role in tet operator recognition by a 'loss of contact' analysis with 16 operator variants. One class of amino acids consisting of T27 and R28 in the first alpha-helix and L41, Y42, W43 and H44 in the recognition alpha-helix are quantitatively most important for wild-type operator binding. These residues are probably involved in the structural architecture of the motif. A second class of residues is quantitatively less important for binding, but determines specificity by forming base pair specific contacts to three positions in tet operator. This property is most clearly demonstrated for Q38 and P39 and to a lesser extent for T40 at the N terminus of the recognition alpha-helix. The contacted operator base pairs indicate that the N-terminus of the recognition alpha-helix is located towards the palindromic center in the repressor-operator complex. Although the orientation of the recognition alpha-helix in the Tet repressor-tet operator complex is inversed as compared with the lambda- and 434 repressor-operator complexes, the reduced operator binding of the TA27 mutation in the first alpha helix suggests that the hydrogen bonding networks connecting the two alpha helices may be similar in these proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756722 TI - Antisense SCL suppresses self-renewal and enhances spontaneous erythroid differentiation of the human leukaemic cell line K562. AB - The SCL gene encodes a member of the helix-loop-helix family of transcription factors that have been implicated in regulation of differentiation and development. Although SCL mRNA is not detectable in normal thymocytes or peripheral T-lymphocytes, transcriptional activation occurs in T-cell tumours. A clue to the normal function of SCL has come from demonstration of high levels of SCL mRNA in erythroid cells. To illuminate the function of SCL in the erythroid lineage, an antisense SCL construct was introduced into the human erythroleukaemia cell line, K562. Cells electroporated with a vector containing antisense SCL grew more slowly than control cells which had received vector alone. Non-specific toxicity was excluded by showing that antisense SCL did not influence growth of Raji cells, a B-cell line that does not express endogenous SCL mRNA. Suppression of K562 growth was accompanied by increased spontaneous erythroid differentiation as measured by benzidine staining. K562 cells containing antisense SCL produced smaller colonies in agar and exhibited reduced clonogenicity compared with control cells. In addition, experiments in which K562 colonies were recloned showed that antisense SCL profoundly suppressed self renewal of K562 cells. These data provide the first evidence that SCL promotes self-renewal in an erythroid cell line and raise the possibility that SCL may function to regulate proliferation of normal erythroid cells. PMID- 1756723 TI - Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus. AB - The transcription factor NF-kappa B binds to DNA as a heterodimer composed of two subunits of 50 kDa (p50) and 65 kDa (p65). p50 contains a DNA binding and dimerization domain and represents a truncated form of a 105 kDa (p105) precursor molecule. We show here that in different cell types the p105 precursor as well as the processed p50 coexist in the cytoplasm, but that only the latter enters the nucleus. The cytoplasmic retention of the precursor molecule is controlled by a small region in its C-terminal part. We show that this region is responsible for the observed lack of DNA binding of the p50 precursor and controls the extent of processing of the precursor to the mature form. We also present evidence that a stretch of four basic amino acids, similar to a sequence found in the other proteins belonging to the rel/NF-kappa B family, is required for translocation of the processed p50 protein into the nucleus and thus could be the target for the retention mechanism. PMID- 1756724 TI - Changes in NF-kappa B and ISGF3 DNA binding activities are responsible for differences in MHC and beta-IFN gene expression in Ad5- versus Ad12-transformed cells. AB - Changes in MHC class I expression are frequently observed in tumors, which represents at least one mechanism by which tumor cells escape immune surveillance. MHC class I expression is often suppressed in type 12 adenovirus (Ad12)-transformed rodent cells, but is highly induced in Ad5-transformed cells. This difference helps to explain why Ad12 but not Ad5 can induce tumors in immunocompetent syngeneic rats. In this report we demonstrate that only Ad5- but not Ad12-transformed rodent fibroblasts constitutively express beta-IFN which results in ISGF3 factor induction, and stimulation of MHC class I expression. Furthermore, we demonstrate that in contrast to Ad12-transformed cells, Ad5 transformed cells show constitutive levels of nuclear NF-kappa B-like DNA binding activity. This is of particular interest since both the beta-IFN and the MHC class I promoters contain an NF-kappa B DNA binding site. Thus, high levels of MHC class I expression in Ad5-transformed cells are due to a combinatorial stimulation of two cis-regulatory sequences of the MHC class I promoter: the NF kappa B binding site and the interferon stimulated response element (ISRE), which binds the ISGF3 factor complex. The failure of Ad12-transformed cells to activate this pathway explains their low levels of MHC class I expression and their greater oncogenicity. PMID- 1756725 TI - HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities. AB - We have looked for the binding of several HOX4 complex homeoproteins in the genomic region containing the HOX4C promoter, between the human HOX4C and HOX4D genes. The HOX4C, HOX4D and Hox-4.3 homeoproteins bind to a phylogenetically highly conserved DNA fragment, which is located in the proximal part of this intergenic region and contains multiple binding sites for these HOX4 proteins. Using cotransfection experiments, we show that this endogenous DNA sequence can mediate transactivation by the HOX4D and HOX4C proteins and that this effect requires the presence of TAAT-related binding sites. The Hox-4.3 protein, in contrast, is unable to activate and can repress the activation observed with the two other proteins. These results show that the HOX4D and HOX4C genes are genuine sequence-specific transcription factors and suggest that, as in Drosophila, cross regulatory interactions between these genes might be essential for their proper expression. PMID- 1756726 TI - HIV-1 Tat protein promotes formation of more-processive elongation complexes. AB - The Tat protein of HIV-1 trans-activates transcription in vitro in a cell-free extract of HeLa nuclei. Quantitative analysis of the efficiency of elongation revealed that a majority of the elongation complexes generated by the HIV-1 promoter were not highly processive and terminated within the first 500 nucleotides. Tat trans-activation of transcription from the HIV-1 promoter resulted from an increase in processive character of the elongation complexes. More specifically, the analysis suggests that there exist two classes of elongation complexes initiating from the HIV promoter: a less-processive form and a more-processive form. Addition of purified Tat protein was found to increase the abundance of the more-processive class of elongation complex. The purine nucleoside analog, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibits transcription in this reaction by decreasing the efficiency of elongation. Surprisingly, stimulation of transcription elongation by Tat was preferentially inhibited by the addition of DRB. PMID- 1756727 TI - Transcriptional termination between the closely linked human complement genes C2 and factor B: common termination factor for C2 and c-myc? AB - We have demonstrated, using a combination of nuclear run-off and poly(A) site competition assays, that transcriptional termination occurs between the closely spaced human complement genes, C2 and Factor B, soon after the C2 poly(A) site. A comparison of the C2 termination signal with a functionally similar sequence downstream of the human alpha 2 globin gene reveals that both signals function in an orientation dependent manner, with subfragments of the whole signal displaying partial effects. In the case of the C2 termination sequence a protein binds within it, and is partially responsible for the termination effect. We further demonstrate that the same (or closely related) protein binds to the ME1a1 site in the murine c-myc promoter, which has been implicated in c-myc attenuation. We suggest that the termination/pause sequences positioned downstream of a gene's poly(A) site may constitute the general signals that elicit transcriptional termination in genes transcribed by RNA polymerase II. PMID- 1756728 TI - The DNA binding and oligomerization domain of MCM1 is sufficient for its interaction with other regulatory proteins. AB - The MCM1 gene encodes an essential DNA binding protein that, in cooperation with the transactivators alpha 1 and STE12 and the repressor alpha 2, confers mating specificity to haploid yeast cells. We show that the amino-terminal third of the MCM1 protein is sufficient for the physical interaction with these factors. A strain expressing just 98 amino acids encompassing the oligomerization and DNA binding domains of MCM1 is viable and mating competent. This motif exhibits considerable similarity to a domain of the mammalian transcription factor SRF. A 98 amino acid hybrid gene coding for the MCM1 DNA binding domain and SRF dimerization domain is sufficient for viability but not for the expression of mating type specific genes. In vitro binding studies suggest that a region of approximately 50 amino acids of MCM1 is essential for providing contacts with alpha 1, alpha 2 and STE12. PMID- 1756729 TI - A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation. AB - MCM1 and SRF bind to the same DNA sequence and form ternary complexes with STE12 and p62TCF, respectively. We show that in gel retardation assays, MCM1 recruits both ternary complex factors whereas SRF interacts only with p62TCF. A protein domain of 90 amino acids, shared by MCM1 and SRF, was found to be sufficient for ternary complex formation. The domain is also required for dimerization and DNA binding. Similar regions are found in other proteins, such as ARG80, Deficiens and Agamous. ARG80 and Agamous exhibit similar DNA binding specificities but do not interact with either STE12 or p62TCF. By exchanging three residues of ARG80 with those of corresponding positions in SRF (residues 198, 200 and 203), the ARG80 protein acquires the ability to recruit p62TCF into a ternary complex. Likewise, the substitution of four SRF amino acids by MCM1-derived residues (amino acids 73, 75, 77 and 78) confers on SRF the ability to interact with STE12. Thus, we have identified specific amino acids in MCM1 and SRF that are critical for ternary complex formation and which map to equivalent positions within the shared domains. Therefore, the structural basis for specific protein protein interaction appears to be conserved in evolution between a class of transcription factors. PMID- 1756730 TI - Depletion of U3 small nucleolar RNA inhibits cleavage in the 5' external transcribed spacer of yeast pre-ribosomal RNA and impairs formation of 18S ribosomal RNA. AB - Multiple processing events are required to convert a single eukaryotic pre ribosomal RNA (pre-rRNA) into mature 18S (small subunit), 5.8S and 25-28S (large subunit) rRNAs. We have asked whether U3 small nucleolar RNA is required for pre rRNA processing in vivo by depleting Saccharomyces cerevisiae of U3 by conditional repression of U3 synthesis. The resulting pattern of accumulation and depletion of specific pre-rRNAs indicates that U3 is required for multiple events leading to the maturation of 18S rRNA. These include an initial cleavage within the 5' external transcribed spacer, resembling the U3 dependent initial processing event of mammalian pre-rRNA. Formation of large subunit rRNAs is unaffected by U3 depletion. The similarity between the effects of U3 depletion and depletion of U14 small nucleolar RNA and the nucleolar protein fibrillarin (NOP1) suggests that these could be components of a single highly conserved processing complex. PMID- 1756731 TI - Cleavage and polyadenylation factor CPF specifically interacts with the pre-mRNA 3' processing signal AAUAAA. AB - Cleavage and polyadenylation factor (CPF) is required for the cleavage as well as for the subsequent polyadenylation reaction during 3' processing of messenger RNA precursors. Here, we have investigated the interaction of CPF and poly(A) polymerase with short RNA substrates. CPF activates poly(A) polymerase to elongate RNA primers carrying the canonical hexamer recognition signal AAUAAA. CPF specifically binds to such RNA as shown by gel mobility shift assays and competition experiments. Upon binding of CPF, two polypeptides of 35 kDa and 160 kDa can be covalently crosslinked to the RNA by irradiation with UV light. These polypeptides may correspond to the smallest and the largest subunit contained in purified CPF fractions. In addition, chemical modification-exclusion experiments demonstrate that CPF interacts directly with the AAUAAA recognition signal in the RNA. The entire hexamer signal is involved in binding of CPF since modification of any of its bases interferes with complex formation. PMID- 1756732 TI - Isolation and expression of cDNA clones encoding mammalian poly(A) polymerase. AB - cDNA clones encoding mammalian poly(A) polymerase were isolated with probes generated by the polymerase chain reaction based on amino acid sequences derived from the purified enzyme. A bovine cDNA clone was obtained encoding a protein of 82 kDa. Expression in Escherichia coli resulted in the appearance of a poly(A) polymerase activity that was dependent on the addition of the purified specificity factor CPF and the presence of the polyadenylation signal AAUAAA in the RNA substrate. The activity copurified with a polypeptide of the expected size. A second class of cDNAs encoded a polypeptide of 43 kDa which was closely related to the N-terminal half of the 82 kDa protein. Northern blots showed two mRNAs of 4.2 and 2.4 kb that probably correspond to the two classes of cDNAs, as well as a third band of 1.3 kb. The sequence of the N-terminal half of bovine poly(A) polymerase is 47% identical with the amino acid sequence of the corresponding part of yeast poly(A) polymerase. Homologies to other proteins are of uncertain significance. PMID- 1756733 TI - The temporal and spatial distribution pattern of maternal exuperantia protein: evidence for a role in establishment but not maintenance of bicoid mRNA localization. AB - The exuperantia (exu) gene of Drosophila melanogaster plays a fundamental role in the establishment of polarity of the oocyte and early embryo by ensuring the proper localization of the mRNA of the bicoid (bcd) gene to anterior regions of the oocyte. We have isolated and sequenced the exu gene, sequenced its female specific transcript and a mutant allele of exu that affects primarily exu's female germline function, and determined the temporal and spatial pattern of exu protein expression during oogenesis. The exu protein is basic, with at least one basic residue being identified as necessary for exu function in the female germline, and is present transiently during oogenesis. Our results suggest that exu is not required for the maintenance of bcd mRNA localization during late stages of oogenesis and early embryogenesis, but rather for the establishment of bcd mRNA localization in the developing oocyte. We propose that the exu protein may serve to modify a component that binds bcd mRNA or to modify the bcd message itself, or may perform a role in docking the bcd mRNA at its site of localization in the developing oocyte. PMID- 1756734 TI - A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. AB - In higher eukaryotes, nine aminoacyl-tRNA synthetases are associated within a multienzyme complex which is composed of 11 polypeptides with molecular masses ranging from 18 to 150 kDa. We have cloned and sequenced a cDNA from Drosophila encoding the largest polypeptide of this complex. We demonstrate here that the corresponding protein is a multifunctional aminoacyl-tRNA synthetase. It is composed of three major domains, two of them specifying distinct synthetase activities. The amino and carboxy-terminal domains were expressed separately in Escherichia coli, and were found to catalyse the aminoacylation of glutamic acid and proline tRNA species, respectively. The central domain is made of six 46 amino acid repeats. In prokaryotes, these two aminoacyl-tRNA synthetases are encoded by distinct genes. The emergence of a multifunctional synthetase by a gene fusion event seems to be a specific, but general attribute of all higher eukaryotic cells. This type of structural organization, in relation to the occurrence of multisynthetase complexes, could be a mechanism to integrate several catalytic domains within the same particle. The involvement of the internal repeats in mediating complex assembly is discussed. PMID- 1756735 TI - The retinoblastoma protein is phosphorylated on multiple sites by human cdc2. AB - The retinoblastoma gene product (pRB) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. pRB is phosphorylated in a cell cycle dependent manner, and studies in both actively dividing and differentiated cells suggest that this modification may be essential for cells to progress through the cell cycle. Using tryptic phosphopeptide mapping we have shown that pRB is phosphorylated on multiple serine and threonine residues in vivo and that many of these phosphorylation events can be mimicked in vitro using purified p34cdc2. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has allowed the identification of five sites. S249, T252, T373, S807 and S811 are phosphorylated in vivo, and in each case these sites correspond closely to the consensus sequence for phosphorylation by p34cdc2. This and the observation that pRB forms a specific complex with p34cdc2 in vivo suggests that p34cdc2 or a p34cdc2 related protein is a major pRB kinase. PMID- 1756736 TI - The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe. AB - The wis1+ gene encodes a newly identified mitotic control element in Schizosaccharomyces pombe. It was isolated by virtue of its interaction with the mitotic control genes cdc25, wee1 and win1. The wis1+ gene potentially encodes a 66 kDa protein with homology to the serine/threonine family of protein kinases. wis1+ plays an important role in the regulation of entry into mitosis, as it shares with cdc25+ and nim1+/cdr1+ the property of inducing mitosis in a dosage dependent manner. Increased levels of wis1+ expression cause mitotic initiation to occur at a reduced cell size. Loss of wis1+ function does not prevent vegetative growth and division, though wis1- cells show an elongated morphology, indicating that their entry into mitosis and cell division is delayed relative to wild type cells. wis1- cells undergo a rapid reduction of viability upon entry into stationary phase, suggesting a role for wis1+ in the integration of nutritional sensing with the control over entry into mitosis. PMID- 1756737 TI - p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast. AB - We have investigated the mechanism by which fission yeast p80cdc25 induces mitosis. The in vivo active domain was localized to the C-terminal 23 kDa of p80cdc25. This domain produced as a bacterial fusion protein (GST-cdc25) caused tyrosyl dephosphorylation and activation of immunoprecipitated p34cdc2. Furthermore, GST-cdc25 dephosphorylated both para-nitrophenyl-phosphate (pNPP) and casein phosphorylated on serine in vitro. Reaction requirements and inhibitor sensitivities were the same as those of phosphotyrosine phosphatases (PTPases). Analysis of cdc25 C-terminal domains from a variety of species revealed a conserved motif having critical residues present at the active site of PTPases. Mutation of the cdc25 Cys480 codon, corresponding to an essential cysteine in the active site of PTPases, abolished the phosphatase activity of GST-cdc25. These data indicate that cdc25 proteins define a novel subclass of eukaryotic PTPases, and strongly argue that cdc25 proteins directly dephosphorylate and activate p34cdc2 kinase to induce M-phase. PMID- 1756738 TI - Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication. AB - We have previously demonstrated that B lymphocyte specific somatic mutations are introduced into the variable regions of immunoglobulin kappa transgenes in two independent transgenic mouse lines. The frequency, distribution and nature of these mutations strongly suggest that they arose as a result of the process of somatic hypermutation, which is responsible, in part, for affinity maturation during an immune response. Unexpectedly, in these multiple copy transgenic lines, many of the transgene copies showed no evidence of somatic mutation. This paradox was addressed by determining the sequence of each transgene copy in several B cell hybridomas derived from a mouse line carrying three copies of the kappa transgene. It was found that the somatic hypermutation process in different B cells from the same mouse preferentially targets one, but not the same, transgene copy. We present a model, based on the pattern of this targeting, which links somatic hypermutation to the orientation of the Ig gene relative to the direction of DNA replication. PMID- 1756739 TI - Vaccinia DNA ligase complements Saccharomyces cerevisiae cdc9, localizes in cytoplasmic factories and affects virulence and virus sensitivity to DNA damaging agents. AB - The functional compatibility of vaccinia virus DNA ligase with eukaryotic counterparts was demonstrated by its ability to complement Saccharomyces cerevisiae cdc9. The vaccinia DNA ligase is a 63 kDa protein expressed early during infection that is non-essential for virus DNA replication and recombination in cultured cells. This implies complementation by a mammalian DNA ligase, yet no obvious recruitment of host DNA ligase I from the nucleus to the cytoplasm was observed during infection. An antiserum raised against a peptide conserved in eukaryotic DNA ligases identified the virus enzyme in discrete cytoplasmic 'factories', the sites of virus DNA synthesis, demonstrating immunological cross-reactivity between host DNA ligase I and the vaccinia enzyme. DNA ligase was not detected in the factories of a mutant virus lacking the ligase gene. Despite this, no difference in growth between wild-type (WT) and mutant virus was detectable even in Bloom's syndrome cells which have reduced DNA ligase I activity. However, DNA ligase negative virus showed an increased sensitivity to UV or bleomycin in cultured cells, and the importance of DNA ligase for virus virulence in vivo was demonstrated by the attenuated phenotype of the deletion mutant in intranasally infected mice. PMID- 1756740 TI - DNA replication in cell-free extracts from Drosophila melanogaster. AB - We have developed an efficient in vitro replication system from 0-2 h Drosophila melanogaster embryos. Demembranated Xenopus sperm DNA when incubated in such an extract first becomes enclosed in a nucleus-like structure with a nuclear envelope and a karyoskeleton. It then undergoes one round of semiconservative replication--this replication appears completely dependent on nuclear formation. Up to 30% of input DNA is nucleated in one reaction. Efficient nuclear formation and replication are dependent on a cold treatment step, prior to disruption of the embryos. They also depend on the age of the embryos used. Extracts from older embryos (0-5 h) are capable of nuclear formation, although at a much reduced efficiency, and repair synthesis, but seem to have lost the ability to initiate DNA replication. In addition to replicating sperm DNA this system appears capable of carrying out semi-conservative replication on some plasmids. However, it cannot use these to trigger nuclear formation; replication is only seen if the plasmids are coincubated with sperm DNA. The in vitro formed nuclei have not been observed to trigger nuclear envelope breakdown and entry into mitosis. However, they can re-replicate the DNA if the nuclei are permeabilized. This system should be a useful complement to the previously isolated Xenopus in vitro replication system. In addition the amenability of Drosophila to genetic study should open up new approaches not previously possible with Xenopus. PMID- 1756741 TI - Percutaneous endovascular stenting: development, investigation and application. AB - Percutaneous endovascular stenting (PES), a new and alternative approach of interventional radiologic techniques, has encouraging potentials for management of vascular obstructive diseases. The most important role of PES is to prevent the risk of abrupt closure and to reduce the rate of early and late post angioplasty restenosis (PARS) of PTA. Because of different working mechanisms, various stents show different advantages and disadvantages. Specific indications of PES are: (1) further compensation for failed PTA, (2) management of complications due to PTA and (3) primary treatment of vascular obstructive diseases. Based on a preliminary comparison with atherectomy, laser angioplasty and PTA, PES seems to provide an advantage for long-term patency of large caliber vessels such as iliac arteries, while more significant problems still exist in PES with small caliber vessels such as femoral-popliteal and coronary arteries. Further comparative clinical research is required to establish the utility of PES among other intraluminal techniques of vascular interventions. PMID- 1756742 TI - Influence of negative ultrasound findings on the management of in- and outpatients with suspected deep-vein thrombosis. AB - Real-time ultrasonography (US) was used as a single non-invasive method in the management of 174 patients (56 inpatients and 118 outpatients) with suspected deep-vein thrombosis (DVT). Therapeutic decisions were based on the results of ultrasonography alone. If the US examination was abnormal anticoagulant treatment was started. If the initial US examination was normal, no treatment was given and the patient underwent repeated testing and physical examination after 1 day, 7 days and 3 months. In the outpatient group, 1.3% of the ultrasonographic negative patients developed thromboembolic complications (95% confidence limits, 0.03 7.21%). None of the initial ultrasonographic negative patients developed proximal DVT after 1 day and 7 days. In the inpatient group, 10% of the ultrasonographic negative patients developed thromboembolic complications (95% confidence limits, 1.2-31.7%). In 18% of the ultrasonographic negative patients an alternative, unexpected diagnosis was obtained by ultrasound. The most frequent alternative diagnosis was a popliteal cyst. The results indicate that US alone appears to be a safe diagnostic method in the management of outpatients with suspected DVT. In the inpatient group further research is required for definite recommendations regarding a safe ultrasound follow-up schedule. PMID- 1756743 TI - Ultrasound findings of ganglions of the wrist. AB - Fifty-one patients with a palpable swelling of a wrist or finger of suspected ganglion origin were examined by ultrasound (US). Forty-five were operated on, and a ganglion was found in 35. The ganglions took the form of cysts 0.4-4 cm in diameter (mean 1.4 cm) with a projection into the joint or tendon in 19 cases. Two patients had multiple ganglia, and two a wrist lipoma, one echo-rich and the other echo-poor with a thick wall. One patient had a giant cell tumour of the tendon sheath which was moderately echogenic in appearance, one had carpal tunnel syndrome and a ganglion-like finding at US, one had tenosynovitis and negative US and one had a prominent tendon due to postoperative sequelae, with US showing a longish echo-poor lesion. Two had hypertrophied muscle forming a long echo-poor structure, one had an exostosis and one had no abnormality in the wrist at operation. Our experiences suggest that ultrasound is useful in many cases with impression of a ganglion at palpation showing multiplicity of a lesion or for assisting in differential diagnosis, although a physical examination is mostly sufficient for diagnostic purposes. PMID- 1756744 TI - Ultrasonography of spleen and liver in staging Hodgkin's disease. AB - Ultrasound (US) findings and accuracy in detecting splenic and hepatic involvement were analysed in 137 unselected, untreated patients with Hodgkin's disease. Histology was available from the spleens of 61 patients and the livers of 59 patients. In 20 patients the spleen appeared abnormal at US; containing focal hypoechoic lesions in 14, being enlarged in 13 and inhomogeneous in 2 patients. Most focal lesions were less than 10 mm. The sensitivity of US in detecting involvement of the spleen was 54% and the specificity 100%; the ability of US to detect hypoechoic splenic lesions improved during the study period. Focal hypoechoic hepatic lesions were found in three patients; histological examination of these showed benign changes in one and suspicious finding in the second. In the third the lesion disappeared during chemotherapy. In three cases with definitive histological evidence of liver involvement, US results were false negative. The results indicate a higher diagnostic efficacy for US in the detection of splenic than hepatic involvement by Hodgkin's disease. PMID- 1756745 TI - Importance of a post-therapeutic residue in the prognosis of head and neck rhabdomyosarcoma in children. AB - Enhanced contrast computed tomography (CT) was performed in 23 children treated for head and neck rhabdomyosarcoma (RMS). The CT studies were retrospectively reviewed by two senior radiologists. Analysis of these CT studies revealed to separate groups of patients. One group (12 patients) had a post-therapeutic residue defined as soft tissue thickening at the original site, which remained stable over a period of 3 months and caused no mass effect on adjacent structures. Of these 12, eight showed enhancement at the area of thickening. Nine of these 12 patients relapsed. The other group (11 patients) demonstrated no post therapeutic residue; only three of these patients relapsed. In this study the presence of a post-therapeutic residue was significantly associated with a poor prognosis, using a Fischer's test (P = 0.04). PMID- 1756746 TI - Post-traumatic hemobilia. AB - Four patients with post-traumatic hemobilia were evaluated with arteriography over a 2 year period. In two patients hemobilia was of iatrogenic origin; in particular, one case appeared after a cholecystectomy, and the other was due to placement of a biliary stent with an endoscope. In the other two patients hemobilia was the result of a gun injury. Arteriography of the hepatic arterial system demonstrated two false aneurysms, extravasation of contrast medium through the biliary system in one patient and arterioportal fistula in another patient. It is concluded that arteriography of the hepatic arterial system is the method of choice for the evaluation and the possible treatment of patients with hemobilia. PMID- 1756747 TI - Premature vascular calcification in a case of POEMS syndrome. AB - A patient with classical POEMS syndrome associated with a myeloproliferative disorder is presented, in whom extensive arterial calcification was seen at an early age in the absence of other predisposing factors. Radiographs also demonstrated several small discrete sclerotic foci elsewhere in the skeleton and areas of new bone formation around the spine which were described in previous cases. Histological studies in this patient demonstrated an osteosclerotic solitary plasmacytoma of bone and Castleman's disease of lymph nodes, both of which have previously been causally associated with POEMS syndrome. In addition, dermal infiltration by mast cells was demonstrated. PMID- 1756748 TI - Calcification of peritoneal carcinomatosis from gastric carcinoma: a CT demonstration. PMID- 1756749 TI - Correlation between computed tomography and magnetic resonance imaging in diastematomyelia. AB - Preoperative neuroradiological evaluation of diastematomyelia cases is of vital importance in order to increase surgical success rate. This paper reports the neuroradiological data of diastematomyelia cases in the light of surgical findings, and discusses the efficacy of CT and MRI in the evaluation of patients with diastematomyelia. PMID- 1756750 TI - Computed tomographic myelography characteristics of spinal cord atrophy in juvenile muscular atrophy of the upper extremity. AB - Although atrophy of the lower cervical and upper thoracic cord in juvenile muscular atrophy of distal upper extremity has been reported, the atrophic patterns of the cord, especially in the transverse section, have not been studied extensively. The aim of this study is to clarify the atrophic patterns of the cord by CT myelography (CTM) and to discuss the pathogenesis of cord atrophy. Sixteen patients with juvenile muscular atrophy of distal upper extremity were examined by CTM. Atrophy of the lower cervical and upper thoracic cord, consistent with the segmental weakness, was seen in all patients. Flattening of the ventral convexity was a characteristic atrophic pattern of the cord. Bilateral cord atrophy was commonly observed; eight of 12 patients with unilateral clinical form and all four patients with bilateral form showed bilateral cord atrophy with dominance on the clinical side. There was no correlation between the degree of cord atrophy and duration of symptoms. Flattening of the ventral convexity, associated with purely motor disturbances, reflects selective atrophy of the anterior horns in the cord, which is attributable to chronic ischemia. Cord atrophy proved to precede clinical manifestations. The characteristic atrophy of the cord provides useful information to confirm the diagnosis without long-term observation. PMID- 1756751 TI - Memory and learning disturbances in multiple sclerosis. MRI lesions and neuropsychological correlation. AB - Thirty-five patients with definite multiple sclerosis (MS) were studied. They underwent neuropsychological testing and magnetic resonance imaging (MRI). The MRI findings at different brain areas levels were compared with the neuropsychological findings. A quantitative system was used to measure MRI-MS lesions. In this series, a positive correlation was established between memory and learning disturbances measured by Battery 144, and the lesions measured by MRI (total, hemispheric and, particularly, periventricular lesions). MRI can detect MS lesions, and this study shows that a correlation between MRI and neuropsychological findings is possible if quantitative methods are used to distinguish different MS involvement areas in relation to neuropsychological tasks. These findings suggest that hemispheric lesions in MS produce cognitive disturbances and MRI could be a useful tool in predicting memory and learning impairment. PMID- 1756752 TI - The effect of digital unsharp-mask filtering on the signal-to-noise ratio in computed radiography. AB - The effect of image processing in computed radiography (CR) has been analyzed in many ROC studies. The results have not shown great diagnostic improvements, except in some special occasions. The theoretical effect of image enhancement on the signal-to-noise ratio in CR images has so far not been assessed. Concerning the previous results, the changes induced in the signal-to-noise ratio by digital image processing are certainly of interest. We calculated the signal-to-noise ratio in various conditions according to the principles of the Rose model, using the computerized image data of storage phosphor radiography. Seventy-seven computed radiographs processed by Gaussian unsharp-mask filtering using different kernel widths were analyzed. The signal-to-noise ratio was reduced in all images by more than 40% when the smallest kernels were used, and increased slowly towards the original value with greater kernel sizes. In no conditions did the ratio exceed the original one. The results show that although edges and signal contrast can be enhanced by unsharp-mask filtering, this happens at the cost of increased noise. This might at least in part explain why image processing does not significantly improve the diagnostic information content of a computed radiograph. PMID- 1756753 TI - Vivos mortui docebunt? Reflections 95 years after the discovery of X-rays. PMID- 1756754 TI - Three-dimensional computed tomography of complex craniofacial fractures. PMID- 1756755 TI - Subsequent bilateral occurrence of fibrous breast tumors. PMID- 1756756 TI - Familial hypomelanosis of Ito. AB - Two siblings presented the typical skin changes of hypomelanosis of Ito (HI) associated with mental and cerebellar signs. Their mother showed only the skin changes of HI but no neurological disturbances. HI is a hereditary disorder, in which familiarity may go unnoticed because of the different expressions of neural and cutaneous features. PMID- 1756757 TI - Sleep disorders, pain, and depression in Parkinson's disease. AB - A consecutive series of patients with Parkinson's disease (PD) were examined for the presence of sleep disturbances, pain, and depression. We found that patients with PD and major depression had significantly more sleep disturbances and severe pain than non-depressed patients with PD. Moreover, depression scores accounted for most of the variance in a stepwise regression analysis of the effect of numerous clinical variables on either sleep disorders or pain severity. These findings suggest that depression is the most important factor associated with the common problems of sleep disorder and pain among patients with PD. PMID- 1756758 TI - Tiapride as treatment for certain patients with idiopathic torsion dystonia. AB - Five female patients with idiopathic torsion dystonia (ITD) responded to treatment with tiapride, a selective D-2 dopamine antagonist. Previous treatments with various drugs, including anticholinergics, were ineffective. It is suggested that the previously reported genetic subgroups of ITD respond to different drug regimens. The autosomal dominant group responded to anticholinergics, while the autosomal recessive group responded best to a selective D-2 dopamine antagonist. PMID- 1756759 TI - Regional relationships between focal hypofixation images in 123I-IMP single photon emission computed tomography and epileptic EEG foci in interictal periods in patients with partial epilepsy. AB - Single photon emission computed tomographic (SPECT) brain scans with N-isopropyl (iodine-123)-p-iodoamphetamine were performed in interictal periods in 40 patients with partial epilepsies and normal X-ray CT findings, and the regional relationships between the SPECT abnormalities and interictal epileptic EEG foci were studied. Twenty-six patients (65%) had abnormal SPECT images consisting of one or more focal hypofixation images, i.e., zones of decreased regional cerebral blood flow, while the remaining 14 patients showed normal images. Nineteen (73%) of the 26 patients showed complete or partial regional agreement between the abnormal SPECT findings and the interictal epileptic EEG foci determined from EEGs recorded repeatedly during their clinical course, while the regional relationships with the EEG foci determined from the single EEG recorded just after the SPECT scans or a short interval after the scans showed a lower rate of agreement (13 of 21 patients, 61.9%). These results confirm the utility of SPECT scans in the regional diagnosis of epileptic foci. PMID- 1756760 TI - Focal neurological deficit with sudden onset as the first manifestation of sarcoidosis: a case report with MRI follow-up. AB - Stroke as a presenting manifestation of sarcoidosis has rarely been reported. This contrasts with the frequent anatomopathological findings of cerebrovascular involvement in neurosarcoidosis. We present a patient who developed acutely a right brachiofacial weakness and dysarthria. Pulmonary sarcoidosis was found. A brain CT and magnetic resonance imaging (MRI) scan disclosed multiple bilateral ischemic, mainly subcortical lesions. Despite a favorable clinical evolution under adequate corticotherapy, an MRI performed 3 months later showed an increased number of the previously observed lesions. This observation suggests that in some cases the evolution of central nervous system sarcoid lesions occurs independently from corticotherapy, and that MRI, in spite of its known great sensitivity in detecting those lesions, may not play a role in the follow-up of some patients with neurosarcoidosis. PMID- 1756761 TI - Effect of therapy with oxygen under high pressure on regional cerebral blood flow in the interval form of carbon monoxide poisoning: observation from subtraction of technetium-99m HMPAO SPECT brain imaging. AB - Changes in brain images with single photon emission computed tomography (SPECT) using 99mTc hexamethylpropyleneamine oxime (HMPAO) before and after therapy with oxygen under high pressure (OHP) were measured in a 66-year-old man with the interval form of carbon monoxide (CO) poisoning by a new technique, i.e., subtraction of brain images. This study was performed 187 days after acute CO poisoning, in a state of chronic akinetic mutism that followed a lucid interval. A diffuse, but frontal-dominant, hypoperfusion pattern involving both the gray and white matter was observed in the pre-OHP SPECT image. After OHP, regional cerebral blood flow increased in both the gray and white matter and markedly increased in the frontal cortical regions. The present finding suggests that OHP is effective against the chronic state of the interval form of CO poisoning. PMID- 1756762 TI - Genetic aspects of nonconvulsive status epilepticus. AB - We studied the occurrence of seizure disorders within the immediate family in 3 groups of probands: (1) 64 epileptic children with nonconvulsive status epilepticus (NCSE); (2) 454 epileptic children who have had no episodes of NCSE; (3) 306 healthy children, matched for age and sex. Recurrence of seizures among relatives of epileptic probands without NCSE was significantly higher than among the general population, both in generalized and partial epilepsies. We also observed an increased incidence of convulsions among the relatives of probands with NCSE and the general population; no differences were noted between epileptic children with or without NCSE. These data support the hypothesis that genetic factors play an important role in the etiology of seizure disorders in children with NCSE. PMID- 1756763 TI - Abolition of photoparoxysmal response in progressive myoclonus epilepsy. AB - We have investigated the effect of piracetam on photoparoxysmal responses in 3 patients with progressive myoclonus epilepsy. With doses of up to 10 g/day, elimination of photoparoxysmal responses was achieved in all 3 patients. Corresponding to EEG improvement, the clinical performance improved slightly in 2 patients and definitely in 1 patient when piracetam was added to their medication of valproate and clonazepam. According to our data, medical treatment of myoclonus with piracetam is justified particularly in myoclonus of cortical origin. PMID- 1756764 TI - Temporal influences on relapses of multiple sclerosis. AB - A 5-year retrospective study (January 1981-December 1985) of 87 patients with a known diagnosis of MS who were admitted to the University College Hospital, Galway, Ireland, was carried out. The duration of disease relapse was correlated with the following meteorological factors prevailing about the period of relapse: (a) temperature--mean daily, absolute maximum, absolute minimum; (b) rainfall; (c) relative humidity, and (d) sunshine and global radiation. Highly significant positive correlations were found between relapse duration and temperature variables, total number of sunshine hours and global radiation. Negative correlations were found between relapse duration and both rainfall and relative humidity. Relapses were of longer duration in the middle months of the year. PMID- 1756765 TI - Marked hypokalemic rhabdomyolysis with myoglobinuria due to diuretic treatment. AB - A 74-year-old male was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia resulted from diuretic treatment. He had no family history of myopathy, and no diarrhea and vomiting. The neurological examination revealed painful quadriplegia. The blood pressure was 160/74 mm Hg. Laboratory examination showed hypokalemic and hypochloremic metabolic alkalosis (serum K 1.5 mEq/l, serum Cl 89 mEq/l, base excess + 20.9, HCO3- 44.9 mmol/l, pH 7.563) and marked elevations of serum CPK, LDH, GOT, GPT and myoglobin. Endocrinological and renal functions were normal. Muscle biopsy revealed marked necrosis with remarkable phagocytosis and vacuolar degeneration. The cessation of diuretics and intravenous infusion of potassium chloride resulted in a marked improvement in clinical and laboratory findings. The diuretics-induced hypokalemic myopathy is rare in the literature. PMID- 1756767 TI - A case of idiopathic palatal myoclonus: treatment with sodium valproate. AB - We describe a case of idiopathic palatal myoclonus with normal CT and NMR results, especially of the region of the inferior olive. The effective treatment with sodium valproate is reported and its relation with GABA is discussed. PMID- 1756766 TI - Neuro-Behcet: acute and sequential aspects by MRI and MRS. AB - Three patients with neuro-Behcet underwent MRI and MRS during acute illness. After therapy, MRI and MRS were performed in 3 and 1 patients, respectively. MRI revealed a marked improvement of the initial lesion in 2, a complete remission in 1 patient. MRS showed a reduction of the N-acetyl-aspartate (NAA)/phosphocreatine (CR) ratio within the acute lesion in all patients and a normalization in the follow-up spectrum of the examined patient. PMID- 1756768 TI - Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis. AB - Single photon emission computed tomography assessments were conducted in normal controls (n = 25), patients with unilateral cerebellar infarctions (n = 4), patients with olivopontocerebellar atrophy (OPCA; n = 15) and patients with Friedreich's ataxia (FA; n = 6). In subjects with unilateral cerebellar infarctions, crossed cerebellar-cortical diaschisis was observed: reduced cerebellar hexamethylpropyleneamine oxime (HMPAO) uptake was invariably accompanied by a diminution of HMPAO in the contralateral basal ganglia and frontoparietal cortex. OPCA and FA patients had various degrees of decreased HMPAO uptake in both the cerebellum and cerebral hemispheres. PMID- 1756769 TI - Refractory tonic generalized status epilepticus. Report of a case of exceptionally prolonged duration. AB - A generalized tonic status epilepticus persisting for 5 months in a young adult previously affected only by tonic-clonic seizures is described. The syndromic classification of the case remains unsettled. PMID- 1756770 TI - Clinical-radiological correlation in the evolution of a neuro-Behcet's syndrome: case report. PMID- 1756771 TI - Orofacial and respiratory tardive dyskinesia: potential side effects of 2 dimethylaminoethanol (deanol)? AB - A case of essential tremor since early adultness is presented, which has been treated successfully with the acetylcholine precursor 2-dimethylaminoethanol (deanol) for 10 years. Development of a marked dyskinesia syndrome affecting predominantly orofacial and respiratory musculature has been noticed with this medication. Partial remission after discontinuation and a favorable response to anticholinergics are suggestive of an adverse drug effect. PMID- 1756772 TI - Hydrocephalus in Guillain-Barre syndrome. AB - Hydrocephalus developed in a 16-year-old boy with a severe Guillain-Barre syndrome and was demonstrated by computerized tomography (CT) and magnetic resonance imaging. No papilledema was observed. The spontaneous resolution of hydrocephalus was achieved in a 6-month period. Ventricular changes were followed by CT scan. PMID- 1756773 TI - Use of CT in epilepsy: does it matter how long you wait? AB - Computer tomography (CT) of the brain is of value for finding potentially correctable lesions in adult patients with new onset seizures. The value of CT is unknown, however, for finding such lesions in adult chronic epileptic patients without prior CT. We compared a group of 177 adult patients who had CT within a year from the onset of seizures to a group of 93 patients who had a history of seizures for more than a year before CT was performed. In the first group, 33 potentially correctable lesions (19%) were found including 17 tumors. The group with chronic epilepsy had 4 (4%) potentially correctable lesions: 3 arteriovenous malformations and 1 meningioma. It seems that CT is of value in discovering potentially removable lesions in chronic epileptic patients, but the likelihood is relatively small. The incidence of stable structural lesions seems to be similar in the two groups. PMID- 1756774 TI - A novel antineuronal antibody in serum and CSF of a patient with motor neuron disease. AB - A patient with motor neuron disease and tonic pupil who had an antinuclear antibody (Ab) in the serum and oligoclonal pattern in IgG in the CSF is described. Sera and CSF from this patient and controls (37 sera and 30 CSF) were screened for an antineuronal Ab using immunoblotting. Only the serum and CSF from this patient contained an Ab to a 70-kD protein in the human spinal cord but not in the human muscle or cerebellar cortex. This patient's serum immunohistochemically stained human and Japanese monkey anterior horn cells but not Japanese monkey dorsal root ganglion. PMID- 1756775 TI - National Institute on Aging, NIH, Workshop on Alternative Animal Models for Research on Aging. AB - The characteristics of various animal models and their relevance for aging studies have been briefly discussed above. These are summarized in tabular form in Tables 1A-1F. The appropriate choice of a model for studying aging depends on a multitude of factors, but the most important characteristics appear to be relevance to human aging, manipulability of the genetic system, availability of physiological characterization data, and ease and cost of husbandry. Whereas most of the organisms discussed here do not satisfy all these criteria, they do offer some special opportunities, for example the ability to study calcium metabolism in female birds; to manipulate the rate of aging in lizards; and to study the genetics of life span in insects (e.g., Drosophila) and/or nematodes. We hope that the information collected here will prove useful to gerontologists with special interests related to human aging, and readers are encouraged to contact the various participants of this workshop for additional information. PMID- 1756776 TI - Isozyme polymorphisms in human diploid cell strains for research on cellular aging. AB - Six human lung diploid cell strains established for the study of in vitro cellular aging (TIG-1, TIG-7, WI-38, IMR-90, MRC-5, MRC-9, and HeLa cells as a control) were studied by cellulose acetate membrane electrophoresis for allozymic differences at 18 enzyme loci. Eight enzyme loci (G6PD, PGM1, PGM3, PepA, PGD, ADA, GLO1, and ME), proved to be informative in establishing unique allozyme genetic signatures for all of the cell strains established from the same species and from the same organ. Changes in the allozyme genetic signatures were not observed throughout the life span of TIG-1 and MRC-9 cells. The allozyme genetic signatures can be used as a quick monitor of cell identification and intraspecific cell contamination. PMID- 1756777 TI - Effect of dietary restriction on the fidelity of DNA polymerases in aging mice. AB - DNA polymerases purified from hepatic tissues of C57BL/6 mice showed an age related decrease in both specific activity and fidelity of the various enzyme forms. Polymerases from dietary restricted mice exhibited less of a decline in specific activity and copied synthetic DNA templates with relatively higher fidelity than did enzymes from animals fed ad libitum. Polymerases treated with inositol-1,4-bisphosphate [I(1,4)P2] showed varying levels of increased activity, with fidelity increases up to 3-fold. These data indicate that aging is associated with decreases in both specific activity and fidelity of DNA polymerases isolated from a nondividing tissue, and that dietary restriction impedes the age-related decline in both specific activity and fidelity of these polymerases. The data further indicate that DNA polymerases may interact with phosphoinositide hydrolysis products resulting in increased specific activity and fidelity of the enzymes. Phosphoinositide interactions with polymerases could constitute an important mechanism moderating the age-related decrease in function and accuracy of DNA polymerases. PMID- 1756778 TI - Individual variability in tail tendon fiber break time in three age cohorts of different strains of mice. AB - Individual variability in mouse tail tendon fiber denaturation in urea was investigated. Differences in break time between fibers within tendons and between tendon groups were examined. Mean break times for each strain increased with age with the shorter-lived DBA/2 mice exhibiting higher break times within age cohorts than the C57BL/6 animals. Fibers from the two ventral tendon groups had consistently higher break times than those from the two dorsal groups, implying differential rates of collagen maturation between these two areas within the tail. Histological examination revealed conspicuous morphological dorsal/ventral differences in tendon number, proximity to a major blood vessel, and the amount of surrounding muscle tissue. These findings have methodological and experimental design implications for the use of tail tendon break time (TTBT) as a biomarker of aging. Furthermore, they suggest possible physiological mechanisms for differential rates of collagen aging. PMID- 1756779 TI - Effect of subordinance, lack of social hierarchy, and restricted feeding on murine survival and virus leukemia. AB - When caged in groups of three and fed ad libitum, dominant male mice survived longer than subordinate group members which again lived longer than males caged in groups of nine, among whom no rank order was established. In groups of nine the social structure was not affected when the food supply was reduced to the lowest level not affecting survival, but in groups of three, food reduction made the survival of both dominant and subordinate animals drop to a level matching that of groups of nine. After challenge with a small dose of Moloney virus, leukemia developed among ad libitum fed subordinate mice in groups of three and members of groups of nine, but not among the dominant animals. Food restriction enhanced the leukemia incidence, but dominant animals continued to go free. We conclude that subordinance and also lack of social hierarchy result in a higher incidence of virus induced leukemia, that severe food restriction does the same, and that the effect of social order on leukemia development prevails even under feeding conditions that nearly abolish group-related differences in survival. PMID- 1756780 TI - Ascorbic acid in Drosophila and changes during aging. AB - The ascorbic acid content of Drosophila melanogaster was found to be high in the absence of a dietary source. The amount of ascorbic acid per fly declined with aging in both the Oregon R and Swedish C strains. The median life span at 25 degrees C was 45 days for Swedish C and 59 days for Oregon R. The amount of ascorbic acid in Swedish C flies (0.078 micrograms/fly) was higher than that for Oregon R (0.058 micrograms/fly) for newly emerged flies but the rate of decline with aging was greater for Swedish C than Oregon R. The decline in ascorbic acid content with aging was 70.4% for Swedish C versus 19.9% for Oregon R. A brief cold shock was found to significantly increase the amount of ascorbic acid in Oregon R flies. Feeding the precursor of ascorbic acid synthesis, L gulonolactone, did not improve the life span. Life-time feeding of ascorbic acid did not improve the life span of either Swedish C or Oregon R flies. PMID- 1756781 TI - An alternative explanation for anomalies in "soluble lipofuscin" fluorescence data from insects, crustaceans, and other aquatic species. AB - Published attempts to extract lipofuscin from crustaceans and fish to assess age for fisheries research purposes have used essentially the same extraction methodology applied to insects, but have neither shown a conclusive age dependence of spectrally similar fluorescence nor proved its association with lipofuscin. The reported lipofuscin solvent extraction method for fleshflies, Sarcophaga bullata, was manipulated by varying wash volume. This revealed that almost all age-dependent blue fluorescent material persisting in lipid fractions was actually pteridine-like. This finding was consistent with some previous independent results for Musca domestica. Examination of reported lipofuscin extraction protocols for other insects suggested that this problem was probably widespread. The pteridines are known to occur in unusually high amounts in insects, accumulating with age specifically in some members of this group by storage excretion, probably as a terrestrial water conservation strategy. In addition, there is growing evidence in the gerontological literature for other groups that solvent extracted blue fluorescence is not a true measure of lipofuscin content in tissues. These findings provide considerable insight into anomalies in putative lipofuscin fluorescence data between the insects and various aquatic species and suggest that there may be little basis for expectations of age-dependent fluorescence from aquatic species when the same gross extraction and crude purification methods are used. PMID- 1756782 TI - Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. PMID- 1756783 TI - Bi-versus monohemispheric performance in split-brain and partially split-brain macaques. AB - Experiments comparing binocular with monocular abilities of monkeys working on visual mnemonic tasks were performed. First, it was shown that even in split brain monkeys performance was more accurate when both hemispheres were utilized than when the task was performed with only the single (better) hemisphere. Some form of noncommissural integration is thus possible. However, when the forebrain commissures are present, as in four other animals (with only optic chiasm transected) it was shown that integration occurs via callosal mechanisms as well. This was demonstrated by the fact that here, too, binocular performance was normally more accurate than monocular performance, but when different images to be remembered were presented concurrently to the two eyes, the binocular advantage was lost. Finally, in three monkeys with only the anterior commissure allowing interhemispheric communication the superiority of binocular assessment remained even when the two hemispheres simultaneously received such differing images. PMID- 1756784 TI - Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: immunohistochemical study of neurons, astrocytes and serum-protein extravasation. AB - The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion fixed, and brains processed for immunohistochemical staining of SNR. Nissl staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48-72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus. PMID- 1756785 TI - Repetitive firing properties of putative dopamine-containing neurons in vitro: regulation by an apamin-sensitive Ca(2+)-activated K+ conductance. AB - Intracellular recording techniques were used to study the effects of apamin (APA), a selective inhibitor of one type of Ca(2+)-activated K+ channel, on the electroresponsive properties of dopamine (DA)-containing neurons within the zona compacta of the substantia nigra (SNc) in rat. Bath application of APA (1 microM) blocked the slow component of a complex post-spike afterhyperpolarization (AHPs) without affecting other characteristics of the action potential. Blockade of AHPs was accompanied by an increase in the number and frequency of action potentials evoked by depolarizing current pulses. However, APA failed to affect the cellular mechanisms underlying spike frequency adaptation or post-stimulus inhibitory period. These data indicate that AHPs can exert a strong influence on the interspike interval but is probably not involved in regulating slower adaptive neuronal responses. PMID- 1756786 TI - Viewer-centred and object-centred coding of heads in the macaque temporal cortex. AB - An investigation was made into the sensitivity of cells in the macaque superior temporal sulcus (STS) to the sight of different perspective views of the head. This allowed assessment of (a) whether coding was 'viewer-centred' (view specific) or 'object-centred' (view invariant) and (b) whether viewer-centred cells were preferentially tuned to 'characteristic' views of the head. The majority of cells (110) were found to be viewer-centred and exhibited unimodal tuning to one view. 5 cells displayed object-centred coding responding equally to all views of the head. A further 5 cells showed 'mixed' properties, responding to all views of the head but also discriminating between views. 6 out of 56 viewer and object-centred cells exhibited selectivity for face identity or species. Tuning to view varied in sharpness. For most (54/73) cells the angle of perspective rotation reducing response to half maximal was 45-70 degrees but for 19/73 it was greater than 90 degrees. More cells were optimally tuned to characteristic views of the head (the full face or profile) than to other views. Some cells were, however, found tuned to intermediate views throughout the full 360 degree range. This coding of many distinct head views may have a role in the analysis of social signals based on the interpretation of the direction of other individuals' attention. PMID- 1756787 TI - Differential and reversal Pavlovian conditioning in rabbits with mediodorsal thalamic lesions: assessment of heart rate and eyeblink responses. AB - Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD), or sham lesions. These animals were compared on acquisition and reversal of a Pavlovian conditioned discrimination task in which tones were the conditioned stimuli and paraorbital electric shock was the unconditioned stimulus. Eyeblink and heart rate conditioned responses were assessed. Lesions of MD impaired the reversal, but not original acquisition, of the eyeblink discrimination. Heart rate discrimination was somewhat impaired during both acquisition and reversal. There were no differences between lesion and sham animals on control measures assessing general activity, somatomotor shock thresholds, or heart rate unconditioned responses. PMID- 1756788 TI - Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques. AB - To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed. PMID- 1756789 TI - Ganglion cell survival in embryonic rabbit retina transplanted to the midbrain of neonatal rats. AB - Fetal rabbit retinae can grow and differentiate when transplanted to the collicular region of neonatal rats. In addition, the observed survival of retinal ganglion cells within grafts is associated with the extension of axons into the superior colliculus of the host brain, suggesting that the factors influencing the guidance of axons and the survival of ganglion cells may be homologous across different mammalian orders. PMID- 1756790 TI - Factors affecting higher-order movement planning: a kinematic analysis of human prehension. AB - Past studies of the kinematics of human prehension have shown that varying object size affects the maximum opening of the hand, while varying object distance affects the kinematic profile of the reaching limb. These data contributed to the formulation of a theory that the reaching and grasping components of human prehension reflect the output of two independent, though temporally coupled, motor programs (Jeannerod 1984). In the first experiment of the present study, subjects were required to reach out and grasp objects, with or without on-line, visual feedback. Object size and distance were covaried in a within-subjects design, and it was found that both grip formation and reach kinematics were affected by the manipulation of either variable. These data suggest that the control mechanisms underlying transport of the limb and grip formation are affected by similar task constraints. It was also observed that when visual feedback was unavailable after movement onset subjects showed an exaggerated opening of their hands, although grip size continued to be scaled for object size. The question remained as to whether the larger opening of the hand during no-feedback trials reflected the lack of opportunity to fine-tune the opening of the hand on-line, or the adoption of a strategy designed to increase tolerance for initial programming errors. To address this question, a second experiment was carried out in which we manipulated the predictability of visual feedback by presenting feedback and no-feedback trials in a random order. In contrast to the situation in which feedback and no-feedback trials were presented in separate blocks of trials (Exp. 1), in the randomly-ordered series of trials presented in Exp. 2, subjects always behaved as if they were reaching without vision, even on trials where visual feedback was continuously available. These findings suggest that subjects adopt different strategies on the basis of the predictability of visual feedback, although there is nothing to suggest that this takes place at a conscious, or voluntary, level. The results of both experiments are consistent with the notion of a hierarchically-organized motor control center, responsible for optimizing performance under a variety of conditions through the coordination of different effector systems and the anticipation of operating constraints. PMID- 1756791 TI - Listing's law for eye, head and arm movements and their synergistic control. AB - We have recorded eye, head, and upper arm rotations in five healthy human subjects using the three-dimensional search coil technique. Our measurements show that the coordination of eye and head movements during gaze shifts within +/- 25 deg relative to the forward direction is organized by restricting the rotatory trajectories of the two systems to almost parallel planes. These so-called "Listing planes" for eye-in-space and head-in-space rotations are workspace oriented, not body-fixed. Eye and head trajectories in their respective planes are closely related in direction and amplitude. For pointing or grasping, the rotatory trajectories of the arm are also restricted to a workspace-oriented Listing plane. During visually guided movements, arm follows gaze, and the nine dimensional rotatory configuration space for eye-head-arm-synergies (three degrees of freedom for each system) is reduced to a two-dimensional plane in the space of quaternion vectors. PMID- 1756792 TI - Transcranial magnetic brain stimulation: lack of oculomotor response. AB - We have investigated whether eye movements can be evoked by transcranial magnetic brain stimulation (TMS) from frontal, precentral, posterior- and inferior- parietal, occipital and temporal positions of the stimulating coil. Our findings were negative, even for structures concerned with voluntary eye movements, such as the frontal eye field (FEF) and the inferior parietal lobe (IPL). The lack of oculomotor responses after stimulation of the cortex shall be discussed in the following context: (1) Low-threshhold intracortical stimulation experiments suggest that in functional terms, the FEF is confined to small areas which are extend to the floor of sulci. TMS does not reach these structures to a sufficient extent. Furthermore efferent connections of the cortex to the paramedian pontine reticular formation (PPRF) seem to be polysynaptic. (2) The function of the cortex in rapid eye movement is to analyze and process conditions with differing functional requirements, rather than to directly generate saccades. TMS does not elicit oculomotor responses, demonstrating again that the role played by the cortex in eye movement is not analogous to the role of the somatic motor cortex in controlling skeletal movements. PMID- 1756793 TI - Transcranial stimulation of the human frontal eye field by magnetic pulses. AB - Single transcranial magnetic pulsed stimuli were applied over the cortical area of the putative right frontal eye field (FEF) in 11 healthy subjects. An especially designed figure of eight shaped twin coil was used, to focus the stimulus, the strength of which was adjusted to the individual motor threshold of the left hand muscles. Eye positions and movements were recorded by an infrared reflection technique. Three different experiments were performed: 1. Stimulation during different primary gaze position did not evoke any discernible eye movement. 2. Stimulation just prior to visually elicited horizontal saccades did not cause a significant alteration of the latency, velocity, or amplitude of the saccades. 3. Only stimulation during an antisaccade task induced a significant latency prolongation, when the stimulus was applied between 50 to 90 ms after the target flashed up. This latency prolongation was found in all subjects for the antisaccades to the right, with a statistically significant average latency difference of +66 +/- 55.5 ms. In contrast, the antisaccades to the left were prolonged in the female subjects only by an average of +98 +/- 41.8 ms (p = 0.0064), whereas in the male subjects they did not alter with stimulation (average difference: -3 +/- 41.9 ms, p = 0.753). Significant latency prolongations were only obtained when the magnetic FEF stimuli were applied within a vulnerable period, which varied from subject to subject. PMID- 1756794 TI - Coincidence of "ladder-like patterns" in distributions of monoaminergic terminals and sympathetic preganglionic neurons in the rat spinal cord. AB - A ladder-like pattern of distribution of sympathetic preganglionic neurons (SPNs) was compared with that of monoaminergic terminals in the upper thoracic spinal cord of the rat. SPNs were identified by a retrograde labeling with cholera toxin subunit B (CTb) injected into the superior cervical ganglia of both sides. Monoaminergic terminals were stained immunohistochemically by using antisera raised against 5-hydroxy-tryptamine (5-HT) or dopamine-beta-hydroxylase (DBH). SPNs showing full dendritic arbors were found in all of the sympathetic preganglionic nuclei. They formed a ladder in the horizontal plane. The nucleus intermediolateralis was connected with the central autonomic nucleus by many transverse dendritic bundles. Photomontages of serial sections of material stained alternatively with antisera against CTb and 5-HT or DBH clearly showed a close correlation between SPNs and monoaminergic terminals. There is no transverse dendritic bundle of SPNs without the accompaniment of monoaminergic terminals. PMID- 1756795 TI - Purkinje cells in the vestibulocerebellum of the pigeon respond best to either translational or rotational wholefield visual motion. AB - Using standard extracellular techniques, the response properties of neurons in the vestibulocerebellum of the pigeon to movement of a wholefield visual stimulus were determined. Complex spike activity of Purkinje cells was modulated in a direction-selective manner by the stimulus and 94% of cells were binocularly driven. Some neurons preferred the same direction of wholefield motion in both eyes, simulating optic flow which results from self-translation, while others preferred the opposite direction in each eye, simulating optic flow resulting from rotation. Four functional classes of neurons were found: (1) Descent cells preferred upward motion in both eyes; (2) Ascent neurons preferred downward motion in both eyes; (3) Roll cells preferred upward and downward motion in the ipsilateral and contralateral eyes respectively; and (4) Yaw cells preferred forward (temporal to nasal) and backward motion in the ipsilateral and contralateral eyes respectively. The observation that these neurons clearly distinguish rotational and translational optic flow patterns suggest they may play an important role in controlling locomotor activities of the pigeon. PMID- 1756796 TI - Changes in the dynamics of the vertical vestibulo-ocular reflex due to linear acceleration in the frontal plane of the cat. AB - The vertical and horizontal components of the vestibulo-ocular reflex (VOR) were recorded in alert, restrained cats who were placed on their sides and subjected to whole-body rotations in the horizontal plane. The head was either on the axis or 45 cm eccentric from the axis rotation. During off-axis rotation there was a change in the linear force acting on the otolith organs due to the presence of a centripetal acceleration along the animal's vertical axis. Otolith forces (defined to be opposite to the centripetal acceleration) directed ventrally with respect to the animal (negative) decreased both the amplitude and time constant of the first-order approximation to the slow phase eye velocity of the vertical vestibulo-ocular reflex (VVOR). Otolith forces directed dorsally (positive) increased the amplitude and time constant. The effects were greater for the up VOR. The asymmetry in the VVOR time constant also depended on the otolith forces, being less in the presence of negative otolith forces that caused the resultant otolith force to move ventrally, towards the direction along which gravity normally acts when the animal is in the upright position. The effects of otolith forces on the up VVOR were independent of whether the animals were tested in the dark or in the light with a stationary visual surround (i.e., during visual suppression). In contrast, the changes in the time constant of the down VVOR were smaller during visual suppression. Simulations of the eye velocity storage mechanism suggest that the gain of the feedback in the storage integrator was modified by the angle between the resultant otolith force and an animal-fixed reference. This could be the animal's vertical, i.e., the direction along which gravity normally acts. For larger angles the feedback was less and the amplitude and time constant of the VVOR increased. The transformation of the otolith input was the same for both the up and down VOR, even though the final effect on the eye velocity was asymmetric (larger for up VOR) due to a separate, asymmetric gain element in the velocity storage feedback pathway. PMID- 1756797 TI - The horizontal vestibulo-ocular reflex during linear acceleration in the frontal plane of the cat. AB - Horizontal and vertical eye movements were recorded in alert, restrained cats that were subjected to whole-body rotations with the horizontal semicircular canals in the plane of rotation and the body centered on the axis or 45 cm eccentric from the axis of rotation. Changes in the horizontal vestibulo-ocular reflex (HVOR) due to the resultant of the linear forces (i.e., gravity and linear acceleration) acting on the otolith organs were examined during off-axis rotation when there was a centripetal acceleration along the animal's interaural axis. The HVOR time constant was slightly shortened when the resultant otolith force was not parallel to the animal's vertical axis. This effect was independent of the direction of the otolith force relative to the direction of the slow phase eye velocity. No effect on the HVOR amplitude was observed. In addition to changes in the HVOR dynamics, a significant vertical component of eye velocity was observed during stimulation of the horizontal canals when the resultant otolith force was not parallel with the animal's vertical axis. The effect was greater for larger angles between the resultant otolith force and gravity. An upward or downward component was elicited, depending on the direction of the horizontal component of eye velocity and the direction of the resultant otolith force. The vertical component was always in the direction that would tend to align the eye velocity vector with the resultant otolith force and keep the eye movement in a plane that had been rotated by the angle between the resultant otolith force and gravity. PMID- 1756798 TI - Delayed reduction in GABA and GAD immunoreactivity of neurons in the adult monkey dorsal lateral geniculate nucleus following monocular deprivation or enucleation. AB - GABA and glutamate decarboxylase (GAD) immunoreactivities were examined in dorsal lateral geniculate nuclei (LGN) of normal monkeys (Macaca fascicularis) and in monkeys that had one eye injected with tetrodotoxin (TTX) or one eye removed 5 days to 4 weeks prior to sacrifice. As seen in previous studies (Wong-Riley and Carroll 1984) monocular TTX injections or enucleation quickly reduced cytochrome oxidase (CO) staining in layers 2, 3 and 5 of the ipsilateral LGN and in layers 1, 4 and 6 of the contralateral LGN. The reduction in CO staining was apparent at all survival times examined. By contrast, GABA and GAD immunostaining in the LGNs were qualitatively normal up to two weeks following enucleation or after 17 days of TTX injections. Quantitative and stereological analyses confirmed that the numerical density and proportion of GABA and GAD neurons do not change in the LGN following two weeks of denervation or deprivation, even though in the same monkeys a reduction in GABA immunostaining was found in deprived-eye columns of area 17. However, with longer survivals, of 3-4 weeks in duration, the number of GABA and GAD immunostained neurons in the deprived/denervated-eye laminae of the LGN was reduced by one-third. These findings demonstrate that the deprivation induced reduction in GABA and GAD immunoreactivity is delayed in the LGN, by comparison with the visual cortex, and suggest that the effects in the LGN may be relayed through the cortex or that neurotransmitter levels may be regulated by different mechanisms in the two sites. PMID- 1756799 TI - Contributions of sodium and chloride to ultrastructural damage after dendrotomy. AB - To determine the contributions of sodium and chloride to ultrastructural changes after mechanical injury, we amputated primary dendrites of cultured mouse spinal neurons in low calcium medium in which sodium chloride had been replaced with either choline chloride or sodium isethionate or sodium propionate. Uninjured cultured neurons were also exposed to the sodium ionophore, monensin. A third set of neurons was injured in medium in which all sodium and calcium chloride had been replaced with sucrose. Neurons injured in low-calcium, low-sodium medium exhibited few ultrastructural changes, except very near the lesion, where there was some dilation of mitochondria and cisternae of the smooth endoplasmic reticulum (SER). Mitochondria in other regions of the neurons developed an electron opaque matrix, and those nearer to the lesion converted to the condensed configuration, characterized by expanded intracristal spaces as well as a dense matrix. If sodium but not chloride was present in the medium, there was some dilation of the Golgi cisternae after injury, as well as some increased electron opacity of the mitochondria. Monensin treated neurons also exhibited dilation of the Golgi cisternae. Neurons injured in sucrose-substituted medium showed none of the changes associated with injury in normal culture medium. These results indicate that sodium influx through the lesion is involved in the dilation of the SER, which is seen even in low-calcium medium, and that a permeant anion, such as chloride, is also involved. This dilation of the SER may result from uptake of calcium released from mitochondria in response to elevated cytosolic sodium. Dilation of the Golgi cisternae appears to be a response only to elevated intracellular sodium. Condensation of the mitochondria after injury is thought to be due to increased demands for ATP synthesis and may involve a "futile cycling" of calcium across the mitochondrial membrane, involving sodium-mediated calcium release in response to elevated intracellular calcium. PMID- 1756800 TI - The neuronal organization of horizontal semicircular canalactivated inhibitory vestibulocollic neurons in the cat. AB - 1. The somatic location and axonal projections of inhibitory vestibular nucleus neurons activated by the horizontal semicircular canal nerve (HCN) were studied in anesthetized cats. Cats were anesthetized with ketamine hydrochloride and pentobarbital sodium. 2. Intracellular recordings were obtained from 11 neck extensor motoneurons which were identified by antidromic activation from the dosal rami (DR) in the C1 segment. Stimulation of the ipsilateral (i-) HCN and the ipsilateral abducens (AB) nucleus evoked IPSPs in the motoneurons. These IPSPs were fully or partially occluded when they were evoked simultaneously. 3. Intracellular recordings were obtained from 8 AB motoneurons. Stimulation of the i-HCN and the i-C1DR motoneuron pool evoked IPSPs in the AB motoneurons. These IPSPs were also partially occluded when they were evoked simultaneously, which implied that some HCN-activated neurons inhibit both i-AB motoneurons and ipsilateral neck motoneurons. 4. Unit activity was extracellularly recorded from 30 vestibular neurons that were activated monosynaptically by i-HCN stimulation. Their axonal projections were determined by stimulating the i-AB nucleus and the i-C1DR motoneuron pool. Eight neurons were activated by both stimuli, and were termed vestibulooculo-collic (VOC) neurons. Their axonal branching was examined by means of local stimulation in and around the i-AB nucleus and the i-C1DR motoneuron pool. Eighteen neurons were antidromically activated from the i-C1DR motoneuron pool but not from the i-AB nucleus. These were termed vestibulo-collic (VC) neurons. Four neurons were activated from the i-AB nucleus but not from the ventral funiculus in the C1 segment, and were termed vestibulo-ocular (VO) neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756801 TI - Ectopic granule cell layer in mouse cerebellum after methyl-azoxy-methanol (MAM) treatment. AB - Previous results from our laboratory (Bejar et al. 1985) indicated that a single injection in mouse pups of the antimitotic/mutagenic agent methylazoxymethanol at postnatal day 5 typically produces hypogranular cerebella with no changes in foliation, in contrast to the severe alterations observed after the more usual injection on the day of birth. Here we report that injection of a higher dose (30 mg/kg) of methylazoxymethanol, always at postnatal day 5, leads to the additional presence of a ectopic cell layer in adult cerebellum. Immunostaining with several antibodies recognizing cell specific proteins ruled out the possibility that these ectopic cells were glial and electron microscopy indicated that they were morphologically mature granule cells. In the molecular layer of other cerebellar areas and apparently unrelated with granule cell ectopia, ectopic Golgi epithelial cells were observed. The reason for the presence of these ectopic cells of different type in the molecular layer was discussed in relation with analogous ectopias obtained by other means. PMID- 1756802 TI - A quantitative study of synaptic contacts on interneurons and relay cells of the cat lateral geniculate nucleus. AB - The relative proportions of synapses made by retinal and extraretinal terminals on interneurons and relay cells in lamina A of the dorsal lateral geniculate nucleus (LGN) of the cat were estimated quantitatively in a sample of 4003 synapses. Processes of interneurons or relay cells were identified by presence or absence of GABA immunoreactivity, respectively, in thin sections treated with post-embedding anti-GABA immunogold. On the basis of ultrastructural features, synaptic terminals were interpreted as belonging to retinal axons, cortical axons or axon collaterals of relay cells. GABAergic terminals were positively identified by being immunoreactive. GABA(-) terminals with heterogeneous and poorly defined characteristics, which could not be identified in the above classes, were grouped together in an "undetermined" category. Among the total synaptic inputs to interneurons, the following relative percentages of synapses from different terminals were obtained: retinal 25%, cortical 37%, GABAergic 26%, axon collaterals 2%, undetermined 6%. The vast majority of retinal terminals synapse on dendritic appendages of interneurons rather than on their dendritic trunks (about 20:1). By contrast, the majority of cortical terminals synapse on dendrites rather than on dendritic appendages (about 5:1). Virtually all axon collaterals synapses were established on dendritic appendages. 17% of the dendritic profiles of interneurons contain synaptic vesicles; many of these profiles were seen in postsynaptic relation to cortical axons and in presynaptic relation with relay dendrites. Given the extensive electrotonic lengths of these cells observed by others, and the expected high electric resistance of the slender stalks that are known to connect the dendritic appendages to interneurons, these results suggest that microcircuits involving the interneuronal dendritic appendages with dendrites of relay cells are under predominantly retinal control. The microcircuits established by presynaptic dendritic trunks with relay dendrites, are under predominantly cortical control. The axonal (spiking) output of interneurons would be under control of the few retinal synapses on proximal dendrites of these cells. Among the total synaptic inputs to relay cells, the following relative percentages of different synapses were obtained: retinal 12%, cortical 58%, GABAergic 24%, axon collaterals 0.3%, undetermined 5%. Relay cells receive twice the number of cortical synapses than interneurons, suggesting that direct cortical excitatory influences on relay cells are more preponderant than cortico-interneuron mediated inhibition on these cells. The observed proportions of dendritic profiles of relay cells and interneurons (80% and 20%, respectively) in the geniculate neuropil are similar to the known proportions of somata of both types of cells in the A laminae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756803 TI - Direct and indirect retinal input into degenerated dorsal lateral geniculate nucleus after striate cortical removal in monkey: implications for residual vision. AB - We removed the striate cortex of one cerebral hemisphere in a macaque monkey, causing almost total retrograde degeneration of the corresponding dorsal lateral geniculate nucleus (dLGN) and extensive transneuronal degeneration of ganglion cells in the corresponding hemi-retina of each eye. The rare surviving geniculate projection neurons were retrogradely labelled by horseradish peroxidase (HRP) from extra-striate cortex and retinogeniculate terminals were labelled by an intraocular injection of HRP. Retinal terminals in the degenerated dLGN made synaptic contact exclusively with the dendrites of interneurons immunopositive for gamma-aminobutyric acid (GABA) in both parvocellular and magnocellular regions of dLGN. As well as being post-synaptic to retinal terminals these vesicle-containing dendrites were pre- and postsynaptic to other similar dendrites, and presynaptic to relay cells. Surviving labelled projection neurons received retinal input indirectly, via both the GABA-immunopositive interneurons and GABA-immunonegative terminals characteristic of those from the superior colliculus. In the degenerated, as opposed to the normal dLGN, about 20% of retinal terminals were GABA-immunopositive and GABA-immunoreactivity was prominently elevated in the ganglion and amacrine cell layers of the degenerated half of the retina. The optic nerve also contained numerous GABA-immunopositive axons but very few such axons were found in a normal optic nerve processed in identical manner. The surviving pathways from the retina must underlie the visual abilities that survive striate cortical removal in monkeys and human patients and may involve the degenerated dLGN as well as the mid-brain. PMID- 1756804 TI - Static firing rates of premotor and primary motor cortical neurons associated with torque and joint position. AB - Single cell activity was studied in the postarcuate premotor area (PMA) and primary motor cortex (MI) of two monkeys performing a load-bearing task with the contralateral hand. Steady-state discharge rates were examined in relation to positional maintenance of the wrist which was held in one of three given positions against graded torques directed towards flexion or extension. Significant and monotonic relationships between tonic firing rate and static torque were found in 41% of 477 MI cells and in only 26% of 470 units studied in PMA. However, for specific cell groups in the PMA the proportion of load-related neurons reached that of the MI samples; this was true for pyramidal tract neurons (PTNs) and for 'non-PTNs' if recorded in their vicinity. The most interesting difference pertains to the range of load over which cells in both areas modulated activity. MI neurons showed steepest change of firing rates over a limited range of small torques around zero external load; the population average displayed a sigmoidal relationship. Proportionally more PMA neurons increased their activity over the entire range of torques examined or showed the highest increase with stronger torques; the population average best fitted a quadratic function. The mean firing rate-torque slope of the PMA population was significantly smaller than that of MI. Many cells in either area were related to both torque and joint position and displayed correlates of length-tension properties of muscle. Change of position sensitivity with torque was found to parallel the rate-torque characteristics in individual neurons. Mean position sensitivity of PMA neurons increased with increasing torques in the 'preferred' direction. In contrast, greatest position sensitivity of the MI population occurred over the range of low torques, which means a clear quantitative dissociation from the muscular activities. The results suggest differential roles of MI and PMA in the control of 'fine' versus 'gross' muscular forces. Undoubtedly, some PMA cell elements (possibly certain output neurons) are involved in aspects of postural control of EMG adjustment to load and joint position. PMID- 1756805 TI - Phasic and tonic responses of premotor and primary motor cortex neurons to torque changes. AB - Responses to torque step perturbation of the wrist were compared in premotor area (PMA) and motor cortex (MI) neurons of the monkey. A substantial portion (39%) of cells recorded from the PMA had phasic responses with onset latencies as short as those found in MI (mostly between 15 and 50 ms). Responsiveness to small perturbations, directional specificity and linear correlation of phasic responses with the velocity of displacement are properties that were essentially present in the PMA. A role of somatosensory feedback to the PMA in accurate and fast up dating of movement is suggested. Tonically sustained responses to torque change (mean latency around 60 ms) were encountered in both areas and preferentially in neurons that had a monotonic load-relationship under steady-state condition. Such cortical responses did not exhibit reflex-like features, i.e. no correlation with amplitude of torque step and resulting displacement. Instead, the new load condition seemed to be represented by the tonic response of any particular neuron in accordance with its individual firing rate-load characteristics. These tonic cortical responses may be involved in the swift and effective adaptation to the actual load. PMID- 1756806 TI - Frontal eye field lesions impair predictive and visually-guided pursuit eye movements. AB - The study initially explored the frontal eye field's (FEF) control of predictive eye movements, i.e., eye movements driven by previous rather than current sensory signals. Five monkeys were trained to pursue horizontal target motion, including sinusoidal targets and "random-walk" targets which sometimes deviated from a sine motion. Some subjects also tracked other target trajectories and optokinetic motion. FEF ablations or cold lesions impaired predictive pursuit, but also degraded visually guided foveal pursuit of all targets. Unilateral lesions impaired pursuit of targets moving in both horizontal orbital fields and in both directions of movement. Saccadic estimates of target motion were generally accurate. The slow-phase velocity of optokinetic pursuit (collected after 54 s of OKN) also appeared normal. Pursuit recovered over 1-3 weeks after surgery but the deficits were then reinstated by removal of FEF in the other hemisphere. Thereafter, a slight deficit persisted for up to 10 weeks of observation in two subjects. The pattern of symptoms suggests that FEF lies subsequent to parietal area MST and prior to the pontine nuclei in controlling pursuit eye movements. PMID- 1756807 TI - Use of plaid patterns to distinguish the corticofugal and direct retinal inputs to the brainstem optokinetic nystagmus generator. AB - We have recorded the direction of optokinetic nystagmus (OKN) elicited by moving plaid patterns in order to dissociate the pathways that mediate horizontal OKN. The plaids used comprised two drifting sinusoidal gratings arranged such that their individual directions of drift were very different from the direction of coherent motion of the overall pattern. The direction of OKN with binocular viewing was close to the mean of the component directions, suggesting a dominant influence of cortical visual neurons that respond to oriented one-dimensional components of the image. But the direction of OKN was consistently shifted slightly towards the direction of motion of the overall pattern, suggesting a secondary influence responsive to pattern direction. OKN recordings obtained during monocular viewing suggest that this secondary influence reflects the direct retinal pathway to the brainstem structures mediating OKN. PMID- 1756808 TI - Electrolytic lesions of the nucleus accumbens in rats which abolish the PREE enhance the locomotor response to amphetamine. AB - The partial reinforcement extinction effect (PREE) refers to the increased resistance to extinction observed in animals trained on a partial reinforcement (PR) schedule compared with those trained on a schedule of continuous reinforcement (CR). It has been suggested that the PREE is dependent upon the integrity of the septo-hippocampal system, but recent evidence has indicated that the role originally proposed for the lateral septal nucleus may in fact be subserved by the nucleus accumbens. Experiment I therefore tested the effects of electrolytic lesions of the nucleus accumbens on the PREE. These lesions abolished the PREE, the abolition resulting from a decreased rate of extinction in the lesion CR rats coupled with an increased rate of extinction in the PR rats. These results clearly implicate the nucleus accumbens in the development of the PREE, and suggest that theoretical models of the PREE based simply upon consideration of septohippocampal interactions need radical revision. The lesion also enhanced running speeds in acquisition in both the CR and the PR groups. Experiment II therefore assessed spontaneous locomotor activity and the locomotor response to amphetamine challenge at two doses. The lesion produced no increase in spontaneous locomotion; an enhanced increase in response to 1 mg/kg amphetamine; and no changes in the stereotyped behaviours induced by 10 mg/kg amphetamine. PMID- 1756809 TI - Response properties of periodontal mechanosensitive units in the cat's thalamus. AB - 1) The response characteristics of periodontal mechanosensitive neurons in the thalamic nucleus were studied by using 15 adult cats anesthetized with alpha chloralose (40 mg/kg, i.v.). 2) 468 periodontal mechanosensitive units (PM units) responsive to light mechanical stimulation of the teeth were recorded from a medioventral aspect of the nucleus ventralis posteromedialis (VPM). Of these neurons, 213 units (45.5%) were slowly adapting, and 255 units (54.5%) were rapidly adapting. 3) The receptive field of the PM units was represented by the number of receptive quadrants on the dental arches of both jaws. About half of the PM units (279, 59.6%) were one-quadrant units. Of these neurons, 69 (14.7%) were single tooth units. Two-quadrant, three-quadrant and four-quadrant units numbered 123 (26.3%), 3 (0.6%) and 63 (13.5%) respectively. Of the PM units detected, 246 units (52.6%), 124 units (26.4%) and 98 units (20.9%) responded to mechanical stimulation of the teeth on only the contralateral side, on only the ipsilateral side and on both sides, respectively. 4) One-quadrant units were distributed mainly in the rostral part of the PM area, and four-quadrant units were found in the caudal part of the PM area. A somatotopic organization for each tooth was not found. 5) The incidence of single tooth units in the thalamus was extremely low, compared with those in the primary afferents and in the trigeminal nuclear complex. Most of the thalamic neurons had larger receptive fields than both the primary afferents and the trigeminal nuclear complex neurons. 6) The high incidence of four-quadrant units at the caudal part of the PM area suggests that many PM fibers converge there. However, it is still unclear whether these fibers come through the intrathalamic neurons or directly from the trigeminal nuclear complex. PMID- 1756810 TI - Differential effects of bicuculline and muscimol microinjections into the vestibular nuclei on simian eye movements. AB - 1.) Eye movements were recorded in four Java monkeys (M. fascicularis) after unilateral microinjections (1 microliter, concentration 1 micrograms/microliter) of the GABA antagonist, bicuculline, and the GABA agonist, muscimol, into oculomotor related regions of the vestibular nuclei. Eye movements were investigated in the dark and light during spontaneous eye movements, vestibular stimulation (sinusoidal: 0.2 Hz, +/- 40 deg/s, and velocity trapezoid: 40 deg/s2 acceleration, 120 deg/s constant velocity), and visual-vestibular conflict stimulation. 2.) Bicuculline and muscimol injections consistently led to specific eye movement changes, which were maximal 5-10 min after bicuculline injection (muscimol 10-30 min), and lasted 90-120 min (muscimol 2-4 h). Control injections with NaCl (0.9%) into the responsive area and with bicuculline 2-3 mm more lateral showed no effect. 3.) Bicuculline induced a spontaneous nystagmus of 40.9 deg/s (average, range 10.5-93 deg/s), beating in 60% of the cases to the contralateral and in 40% to the ipsilateral side. The analysis of the slope of the slow phase gave no evidence for an additional gaze holding deficit. The VOR gain in the dark showed a slight decrease (pre: 0.96; post: 0.86) on average. The time constant of decay for slow phase nystagmus velocity after vestibular ramp stimulation was reduced, reflecting a 'velocity storage' deficit. After bicuculline injections nystagmus suppression in the light and during visual vestibular conflict stimulation was generally well preserved. 4.) After muscimol injections horizontal gaze holding was severely affected. Each saccade was followed by an exponentially decreasing postsaccadic drift with a time constant as short as 250 ms (average 414 ms). The eyes always drifted towards a null position, which generally did not coincide with the midposition of the eye. The null-position could move up to 35 deg to the contralateral or ipsilateral side. The highly distorted eye movements after muscimol injections prevented VOR measurements based on eye velocity. Instead vestibular stimulation led to a shift of the null-position with an amplitude corresponding to a gain (eye position/stimulus position) of 0.17 (average) at 0.2 Hz (+/- 40 deg/s). Vertical eye movements did not show a major gaze holding deficit. 5.) From the experiments it can be concluded that the inhibitory transmitter GABA plays an important role for eye movement generation within the vestibular nuclei. Bicuculline induces mainly a vestibular imbalance with little evidence for a neural integrator deficit. In contrast unilateral muscimol injections lead to a complete, reversible loss of function for the common horizontal neural integrator, which converts eye velocity into eye position signals. The accompanying shift of the null-position reflects an additional vestibular imbalance. PMID- 1756811 TI - A transient projection from the trigeminal brainstem complex to the superficial layers of the hamster's superior colliculus. AB - Anterograde tracing with the carbocyanine dye, Di-I, was used to describe the normal postnatal development of the projection from the trigeminal (V) brainstem complex to the superior colliculus (SC) in hamster. In adult hamsters, this projection is completely restricted to the deep laminae, primarily the stratum album intermedium. Trigeminal fibers were present in the SC by the day of birth, and at this time, they terminated mainly in the deep layers. However, labelled fibers also extended into the superficial laminae (the stratum griseum superficiale and stratum opticum) reaching as far as the SC surface. Trigeminal projections to the superficial SC laminae were visible as late as postnatal day (P-) 6, but were absent by P-8. During the period when V axons were present in the superficial SC laminae, they could not be detected in the dorsal lateral geniculate nucleus. PMID- 1756813 TI - Functional organization of the auditory thalamus in the guinea pig. AB - The auditory thalamus of the guinea pig was investigated with microelectrode mapping techniques. Pure tones of varying frequencies and amplitudes were used as acoustic stimuli, and frequency tuning curves were recorded from 840 multi-units or single cells. The neurons in ventral nucleus of the medial geniculate body (MGv) respond vigorously to pure tones; they have mostly narrow frequency tuning curves and short response latencies (8-12 ms). The MGv is tonotopically organized: High frequencies (16-21 kHz) are located rostrally; the intermediate frequencies (2.8-11 kHz) lie caudomedial of the high frequencies, while the low frequencies (0.5-2.8 kHz) run as a continuous band from rostrolateral to caudomedial. These data confirm a model of tonotopy of the guinea pig MGv which was based on anatomical data from previous tract-tracing experiments. In these experiments, thalamocortical connections were investigated with retrogradely transported tracers (horseradish peroxidase, fluorescent dyes, Redies et al. 1989b). Dorsal, lateral and in part also ventral to MGv, the neuronal responses to pure tones were often less vigorous than in MGv. Many neurons had broad frequency tuning curves, and in nearly all recordings from this region, the response latencies were longer than 12 ms. A tonotopic organization was not apparent here. From the response properties and the location relative to MGv, we concluded that this area corresponds to the shell nucleus of the MG. PMID- 1756812 TI - Development of the occipital corticotectal projection in the hamster. AB - Anterograde and retrograde labelling with the carbocyanine dye, Di-I, was used to assess the development of the visual cortical projection to the superior colliculus (SC) in pre- and postnatal hamsters. Posterior cortical axons arrive in the SC on postnatal (P-) day one (the first 24 hours after birth = P-0) and begin to arborize in the superficial laminae (the stratum griseum superficiale [SGS] and stratum opticum [SO]) within one day after they enter the tectum. Over succeeding days, the density of the projection increases and numerous labelled fibers are visible throughout the depth of the SGS and SO. Beginning on P-6, there is a decrease in the density of labelled fibers in the upper SGS and by P 10, the laminal distribution of the occipital corticotectal pathway appears adult like. Anterograde tracing with Di-I also revealed the presence of a few corticotectal fibers that crossed the midline in both the SC and posterior commissures to terminate mainly in the superficial tectal laminae contralateral to the injection site. Crossed corticotectal fibers were visible in hamsters aged between P-3 and P-12. Retrograde tracing with Di-I in hamsters killed between P-3 and P-12 demonstrated that both the ipsilateral and crossed corticotectal projections arose exclusively from pyramidal cells in developing lamina V. PMID- 1756814 TI - Cholinergic activation of a population of corneal afferent nerves. AB - The in vivo rabbit cornea was used to investigate the effect of acetylcholine on "free" nerve endings from A-delta and C-fibers in the long-ciliary (corneal) nerve. Extracellular electrophysiologic recordings were obtained from 67 corneal nerve fibers. Acetylcholine in concentrations of 10(-5) to 10(-3) M stimulated a specific population of these corneal afferents that were not activated by mechanical or thermal stimuli. Their conduction velocity was determined to be 1.14 +/- 0.34 m/s (mean +/- SD). The other three previously characterized corneal nerve populations (mechanical, mechano-heat, and cold) were not stimulated by the cholinergic agonists or antagonists. Acetylcholine sensitive afferents were also stimulated by carbachol (10(-5) to 10(-3) M) and nicotine (10(-6) to 10(-4) M) but not by bethanecol (10(-5) to 10(-3) M). Acetylcholine-induced activity was abolished by d-tubocurare (10(-4) M) and kappa-bungarotoxin (10(-6) M). The cAMP analog 8-bromoadenosine 3'5'-cyclic monophosphate activated the same population of chemosensitive C-fibers as acetylcholine. It is concluded that a specific population of C-fiber afferents exist in the rabbit cornea which are stimulated by acetylcholine possibly acting via a neuronal nicotinic receptor. Physiologically, these nerves may be involved in the production of pain following tissue injury or ischemia. PMID- 1756815 TI - Is there a three neuron arc in the cat utriculo-trochlear pathway? AB - The utriculo-ocular pathway was examined in decerebrated and anesthetized cats, in which all the vestibular afferents in the labyrinth, except for those innervating the utricular (UT) macula, had been transected. The UT nerve was stimulated with tungsten electrodes which were insulated except for 200 microns at the tips. Stimulation of the UT nerve evoked a small negative (N1) potential in the vestibular nuclei, with a threshold (N1T) less than 25 microA. The stimulus evoked disynaptic EPSPs in ipsilateral abducens (AB) motoneurons. The threshold and latency of the excitatory postsynaptic potentials (EPSPs) was 1.3 x N1T and 1.2 ms, respectively, in accordance with the data of Schwindt et al. (1973). On the other hand, EPSPs with a clear rising phase and short latency, suggesting the existence of a disynaptic pathway, were never observed in any contralateral trochlear (TR) motoneurons, even when triple shocks at intensities of up to 4 x N1T were applied. This stimulus strength was strong enough to activate the UT nerve. Thus it seems very likely that a disynaptic pathway from the UT nerve to contralateral TR motoneurons, is absent or very poorly organized. PMID- 1756816 TI - Effects of percutaneous stimulation on motor unit firing behavior in man. AB - Motor unit firing behavior in human first dorsal interosseous (FDI) muscle was studied during controlled constant force isometric contractions. The threshold at which motor units were recruited and the mean firing rate at 50% of maximal voluntary contraction (MVC) were evaluated following stimulation of the skin area over the second digit. Stimulation of cutaneous receptors tended to increase the recruitment threshold of most of the motor units recruited under 20% MVC, while high-threshold motor units (those recruited over 30% MVC) generally exhibited a decrease in recruitment threshold. Less dramatic changes in motor unit firing rates were observed, but those motor units recruited over 30% MVC exhibited some increase in firing rate. The relationship between the change in recruitment threshold and change in motor unit firing rate is not rigid and seems to be susceptible to considerable synaptic noise. PMID- 1756817 TI - On a method to detect long-latency excitations and inhibitions of single hand muscle motoneurons in man. AB - The peri-stimulus-time histogram (PSTH) analysis of stimulus-related neuronal spike train data is usually regarded as a method to detect stimulus-induced excitations or inhibitions. However, for a fairly regularly discharging neuron such as the human alpha-motoneuron, long-latency modulations of a PSTH are difficult to interpret as PSTH modulations can also occur as a consequence of a modulated neuronal autocorrelation. The experiments reported here were made (i) to investigate the extent to which a PSTH of a human hand-muscle motoneuron may be contaminated by features of the autocorrelation and (ii) to develop methods that display the motoneuronal excitations and inhibitions without such contamination. Responses of 29 single motor units to electrical ulnar nerve stimulation below motor threshold were investigated in the first dorsal interosseous muscle of three healthy volunteers using an experimental protocol capable of demonstrating the presence of autocorrelative modulations in the neuronal response. It was found for all units that the PSTH as well as the cumulative sum (CUSUM) derived from these responses were severely affected by the presence of autocorrelative features. On the other hand, calculating the CUSUM in a slightly modified form yielded--for all units investigated--a neuronal output feature sensitive only to motoneuronal excitations and inhibitions induced by the afferent volley. The price that has to be paid to arrive at such a modified CUSUM (mCUSUM) was a high computational effort prohibiting the on-line availability of this output feature during the experiment. It was found, however, that an interspike interval superposition plot (IISP)--easily obtainable during the experiment--is also free of autocorrelative features.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756818 TI - Depth-coded motion signals in plaid perception and optokinetic nystagmus. AB - When two sine-wave gratings drift in different directions at the same speed behind a circular window, a single coherent plaid is seen rather than one grating sliding over the other. We find that as the stereo depth separation of the two component gratings increases, the probability of seeing a plaid declines. The gain of the slow phase of vertical optokinetic nystagmus (OKN) also falls as the separation of the components increases. When the two grating components are in the same depth plane, the vertical eye velocity is greater than that of either component. This shows that the OKN is being driven by the plaid, whose vertical speed is roughly twice as fast as the components. We conclude that both perception and OKN are fed by the same motion signal, which arises after binocular combination and after plaid synthesis. PMID- 1756819 TI - Wrist muscle activation patterns and stiffness associated with stable and unstable mechanical loads. AB - The objectives of this study were to examine the effects of load mechanical characteristics and agonist-antagonist muscle cocontraction, on the stretch reflex response of wrist flexor muscles, and to measure the associated wrist stiffness. Subjects were required to maintain a constant wrist angle while operating against flexor loads with different stability characteristics (constant, elastic or unstable). We measured the stretch reflex responses and joint stiffness by applying step displacements of 3 degrees and 10 degrees. Subjects used very little cocontraction of wrist flexor and extensor muscles when the load was constant or elastic, but increased cocontraction dramatically when the load was unstable, in order to increase the wrist stiffness. Although the magnitude of stretch reflex responses also increased with cocontraction, this simply reflected the level of tonic flexor muscle activity. We found no evidence to suggest that phasic stretch reflexes contributed significantly to the joint stiffness in this task. Clear differences in flexor muscle synergy were observed in the presence and absence of cocontraction, particularly when comparing the FCR and FCU muscles. PMID- 1756820 TI - Head acceleration following linear translations in the freely-standing cat. AB - The aim of this study was to determine whether vestibular information related to head acceleration is available for triggering postural responses to perturbations of stance in the freely-standing cat. Linear accelerations of the head were recorded during postural responses evoked by linear translations of the support surface. A consistent initial peak of acceleration was observed at an average latency of 22 ms and magnitude of 0.03 g (g is acceleration due to gravity, 9.8 m/s/s). The acceleration peak preceded the first evoked EMG activity by an average of 24 ms. It was concluded that stimulation of the vestibular apparatus was both adequate and early enough for the vestibular system to have triggered the automatic postural response. PMID- 1756821 TI - Transient increase in glutamic acid decarboxylase mRNA in the cerebral cortex following focal cortical lesion in the rat. AB - In situ hybridization histochemistry (ISHH) was used to study the expression of glutamic acid decarboxylase (GAD) mRNA changes in the rat cerebral cortex following unilateral frontal and somatosensory cortical lesion by devascularisation. 4 days after the lesion, a significant transient increase in GAD mRNA level in the ipsilateral cortex was observed when compared with contralateral, ipsi-sham operated and ipsi-normal control cortices. The change occurred throughout the ipsilateral neocortex, with no significant difference between the magnitude of increase in frontal, parieto-occipital, parieto temporal, cingulate or retrosplenial areas; no obvious change was seen in pyriform, entorhinal or hippocampal cortices. This unexpected GAD mRNA increase in neocortex may be part of a long term adaptive functional alteration and changes in the gene expression of the cerebral cortex following focal cortical injury. PMID- 1756822 TI - Parallel processing of multisensory information concerning self-motion. AB - Cats trained to stand on a platform exhibit postural responses to dynamic tilting that appear to be based on an internal reference model of body geometry and the environment rather than directly on sensory inputs, as in a classical reflex chain. The data presented show an independent control of global variables of limb geometry, the length and the orientation, resulting from a parallel processing of multisensory inputs into separate central representations of body tilt. Limb length and orientation changes have completely different response dynamics and can be decoupled by appropriate manipulation of sensory information about self motion. PMID- 1756823 TI - A quantitative study of the pulsatile parameters of CRH-41 secretion in unanesthetized free-moving rats. AB - Having recently improved the sensitivity of the RIA CRH-41 measurements in perfusates from push-pull cannulas implanted in the rat median eminence, we explored quantitatively the pulsatile parameters of the CRH-41 measured with this technique at 2.5 or 5 min intervals in a series of unanesthetized male rats under basal conditions. The data were analysed by computer using 4 algorithms, i.e. Santen & Bardin, Ultra, Pulsar and Periodogram. Under a basal mean secretion rate of 15.5 pg CRH-41/15 min, the pulsatile pattern of CRH-41 release was statistically assessed with the 4 methods, with a mean pulse frequency of 3.1 c/h, pulse length of 11.6 min and a peak amplitude above mean levels of 4 pg. The respective advantages of the 4 algorithms and the physiological relevance of the neurohormone's pulsatility are discussed. PMID- 1756824 TI - Isochronic transplantation of neonatal grafts in the visual cortex of cats: responsiveness, ocular dominance and specificity of cortical cells to visual stimulation. AB - The visual cortex of adult cats was studied physiologically following neonatal isochronic transplantation of grafts from areas 17,18, which were placed homotopically, in order to reveal their functional integration and thus possible repairing of damaged cortical neuronal circuits. Three homograft cats, in which transplantation was carried out between siblings (228 cortical cells) were compared to 4 animals receiving reimplanted autografts of the equivalent size (131 cells) as well as 3 animals with analogous sectioning of the visual cortex (162 cells) (pseudograft controls). The location of the boundaries between the transplant region and the host were determined using the Nissl's method for staining histological cross sections. Extracellular unit recording revealed typical waveform of the action potentials in the transplanted region and in the surrounding host tissue of all groups of cats. Visual responsiveness in the homograft cats was 17.5% in the transplanted region and 80.4% in the unoperated hemisphere; the corresponding results were 40.3% for the transplanted region and 82.2% for the unoperated hemisphere in the autografts and 23.1% and 73.4% in the pseudografts. The specificity of the cells to visual stimulation as expressed by their orientation and direction specificity, indicated preservation of these properties in the transplanted cats. While all responsive cells in the transplanted region of the homografts were orientation specific, their proportion was 60% in the autografts and 55.5% in the analogous region in the pseudograft controls. As to the direction specific cells, their performance in the grafted region of the grafted cats was even much higher than that of the pseudograft controls. The ocular dominance distribution of the cells showed preservation of binocularity in the transplanted region (90.0% binocular cells) of the homografts; it was however smaller in the equivalent region of the autografts (65.0%) and remarkably reduced (20.0%) in the pseudografts. It was concluded that despite the deafferentation induced during the transplantation procedure, a remarkable visual responsiveness was found in the transplanted region, indicating postoperative recovery. However, the cells there were mainly affected in their activity and less in their specificity to visual stimulation. PMID- 1756825 TI - Selective activation of human soleus or gastrocnemius in reflex responses during walking and running. AB - Phase-dependent reflex modulation was studied by recording the electromyographic (EMG) responses in soleus (SOL) and gastrocnemius medialis (GM) to a 20 ms train of 5 electrical pulses, applied to the sural or tibial nerve at the ankle, in 14 volunteers walking or running on a treadmill. Although both the spontaneous activity and the reflex responses were usually similar for both muscles, instances were identified in which separate control was evident. During walking (4 km/h), activity in SOL started earlier in the stance phase than GM activity. Correspondingly, the amplitude of the reflex responses was larger in SOL than in GM in early stance, both ipsi- and contralateral to the side of stimulation. In some cases, the same stimulus could elicit contralaterally a suppression of GM in synchrony with a facilitation of SOL. These crossed extensor reflexes had a low threshold (1.2 x T) and a latency ranging from 72 to 105 ms. During running (8 km/h or more), responses were seen selectively in GM instead, without concomitant responses in SOL. Such responses had a latency ranging from 82 to 158 ms and they appeared during the first extension phase, at the end of the swing phase. In addition, selective GM responses, with latencies above 200 ms, were seen near the transition from stance to swing during running. These instances of separate reflex control of SOL and GM were correlated with step cycle periods during which the motoneurones of either one of these muscles received more spontaneous activation than the other. Nevertheless, it is argued that premotoneuronal gating must also be involved since the increased amplitude of the crossed SOL responses (in early stance) and of GM responses (at end swing) was not strictly linked to an elevated amount of spontaneous activity during these parts of the step cycle as compared to other parts. PMID- 1756826 TI - Contrast adaptation and contrast gain control. AB - Electrophysiological measurements have shown that contrast adaptation can increase the contrast gain of cortical cells of the cat and the monkey. This implies that adaptation could enhance the contrast discrimination sensitivity. Psychophysical contrast discrimination experiments were performed with and without contrast adaptation. The stimuli were spatially separated stationary Gabor patterns. The pedestal contrast was varied from 6 to 75 per cent. The spatial frequency was 1.5, 5.0 or 20 cpd. After adaptation the contrast detection thresholds are elevated and the subjective contrast is lowered. The contrast discrimination thresholds remain unchanged. PMID- 1756827 TI - Comparisons of the sensation perceived and intradental nerve activity following temperature changes in human teeth. AB - The relationship between the intradental nerve responses and subjective sensory ratings evoked by thermal stimulation of the teeth was studied in man. Recordings were taken from a total of 12 thermally sensitive units from the inferior dental nerve following thermal tooth stimulation, of which seven responded to both heating and cooling, two were exclusively cold-sensitive and three exclusively heat-sensitive. The early and late sensory responses following both cold and heat stimulation of the tooth were observed. The late sensory responses were more unstable than the early sensory responses. The mean threshold of the early sensory responses to tooth cooling was 13.6 +/- 1.9 degrees C (n = 9) and that to heat stimulation was 48.4 +/- 4.8 degrees C (n = 10). The firing frequency of the heat-sensitive, but not the cold-sensitive, units increased linearly in proportion to the increase in magnitude of the early sensory ratings. PMID- 1756828 TI - Express saccades: is there a separate population in humans? AB - It is well known that the latencies of target elicited saccades are significantly reduced when the target onset is preceded shortly by the offset of a fixation point (Saslow 1967). Fischer and Boch (1983) reported the discovery that, with monkeys as subjects, in addition to the general reduction in saccade latencies previously reported, there occurred a separate population of saccades with extremely short reaction times. They termed this population "express saccades", and more recently reported the discovery of an equivalent population of express saccades for humans (Fischer and Ramsperger 1984; Fischer 1987). In this paper, work is reported which confirms the existence of short latency visually guided saccades in humans but questions whether these form a separate population of "express saccades". The conditions used were very similar to those used by Fischer and Bocn. PMID- 1756829 TI - The neurophysiological correlates of colour and brightness contrast in lateral geniculate neurons. II. Adaptation and surround effects. AB - We report on experiments which were undertaken in an attempt to clarify mechanisms underlying the contrast effects of chromatic surround illumination on spectral responsiveness of cells in the parvocellular layers of the LGN (P-LGN cells), that had been demonstrated under standard conditions in the preceding companion paper. The experiments were done in anesthetized macaques (Macaca fascicularis). In some neurons, S-potentials were recorded together with the post synaptic action potentials, and all effects seen in P-LGN-cells were present already in their retinal afferents indicating their retinal origin. The responsiveness of the cells for center stimuli of different wavelengths and during illumination of the receptive field center or the outer surround was determined. Continuous outer surround illumination altered maintained discharge rate (MDR), sensitivity and gain of P-LGN and retinal ganglion cells in the same way and empirically not distinguishable from direct illumination of the receptive field. Responses to surround flashes showed the same dependence on spectral composition as those to center flashes. Adaptation and excitation caused by outer surround illumination (inner diameter 5 degrees, outer diameter 20 degrees) were, in the average, ten times weaker than those exerted by light of the same spectral composition shone directly into the receptive field. Surround effects decreased proportional to r-2. Excitation by outer surround flashes was reduced by adaptation of the receptive field center in the same manner as responses to center flashes. The findings indicate that outer surround light has a direct excitatory and adaptive effect on the excitatory or inhibitory cones feeding into the receptive field. This indicates that straylight from the surround into the center could be responsible for the adaptive and excitatory effects of surround illumination. The straylight fraction from the remote surround into the receptive field must be higher, however, than that estimated from the psychophysically determined point spread function. It comes closer to earlier direct straylight measurements in excised eyes, but may be enhanced by chromatic aberration. If a surround of excitatory colour is flashed simultaneously with an excitatory center stimulus, additivity of center and surround excitation is observed only at low center intensities, while at higher center intensities the gain for center excitation is reduced similar to adaptive gain control. This could be explained by lateral interaction through horizontal connections in the retina, which decays within seconds, while adaptation of the cones feeding into the receptive field center is fully effective only after about 3 s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756830 TI - Hippocampus and the blood supply to TE: parahippocampal pial section impairs visual discrimination learning in monkeys. AB - In the base of each temporal lobe in 4 monkeys (Macaca fascicularis) we sectioned the pia mater in an antero-posterior line along the most medial part of the inferior temporal visual association cortex (area TE), lateral to the parahippocampal cortex. This pial section interrupts the blood flow in branches of the posterior cerebral artery which cross the parahippocampal gyrus en route to area TE. Histologically, the brains of 2 of these animals did not show any abnormalities in cresyl violet stained material, apart from the small cortical damage along the line of the pial section itself. Of the remaining two animals, one had a small unilateral infarct in TE and one had bilateral infarcts in TE. All of these animals were impaired in visual discrimination learning, and the severity of impairment was correlated only imperfectly with the severity of infarction. These results show that pial section along the medial boundary of area TE can affect visual discrimination learning without producing large infarcts. Further, since aspiration lesions of the hippocampal formation require the pia mater to be sectioned in a similar way to that reported here, the effects of such aspiration lesions on visual learning and memory may be mediated in part by effects on TE. PMID- 1756831 TI - Hypertrophy of dopamine neurons in the primate following ventromedial mesencephalic tegmentum lesion. AB - Morphological changes in ventral mesencephalic dopamine (DA) neurons of a monkey sustaining a unilateral electrolytic lesion of the ventromedial mesencephalic tegmentum four years earlier were examined. Substantia nigra (A9) DA neurons lateral to the lesion underwent hypertrophic changes. The mean area of these neurons was enlarged by approximately 30% relative to corresponding neurons in the contralateral substantia nigra. Semi-quantitative immunohistochemical measurements of the intensity of tyrosine hydroxylase-like immunoreactivity (TH li) indicated an increase in the amount of TH-li protein per cell in the hypertrophied neurons. Hypertrophic changes were also observed in ipsilateral A11 DA neurons of the caudal hypothalamus, suggesting that the increase in size was related to transection of the axons of DA neurons as they pass through the midbrain in their projections to target sites. The lesion did not overtly change the density or pattern of the substance P innervation of the substantia nigra, indicating that the striato- and pallido-nigral projections were spared by the lesion. These data suggest that hypertrophy may be a compensatory mechanism of dopaminergic neurons in response to partial lesions of the nigrostriatal system, and thus represent a morphological counterpart to the compensatory biochemical processes effected in response to partial lesions of the striatal dopaminergic innervation. PMID- 1756832 TI - The neurophysiological correlates of colour and brightness contrast in lateral geniculate neurons. I. Population analysis. AB - The colour of an object is changed by surround colours so that the perceived colour is shifted in a direction complementary to the surround colour. To investigate the physiological mechanism underlying this phenomenon, we recorded from 260 neurons in the parvo-cellular lateral geniculate nucleus (P-LGN) of anaesthetized monkeys (Macaca fascicularis), and measured their responses to 1.0 2.0 degrees diameter spots of equiluminant light of various spectral composition, centered over their receptive field (spectral response function, SRF). Five classes of colour opponent neurons and two groups of light inhibited cells were distinguished following the classification proposed by Creutzfeldt et al. (1979). In each cell we repeated the SRF measurement while an outer surround (inner diameter 5 degrees, outer diameter 20 degrees) was continuously illuminated with blue (452 nm) or red (664 nm) light of the same luminance as the center spots. The 1.0-1.5 degree gap between the center and the surround was illuminated with a dim white background light (0.5-1cd/m2). During blue surround illumination, neurons with an excitatory input from S- or M-cones (narrow- and wide-band/short wavelength sensitive cells, NS- and WS-cells, respectively) showed a strong attenuation of responses to blue and green center spots, while their maintained discharge rate (MDR) increased. During red surround illumination the on-minus-off responses of NS- and WS-cells showed a clear increment. L-cone excited WL-cells (wide-band/long-wavelength sensitive) showed a decrement of on-responses to red, yellow and green center spots during red surround illumination and, in the majority, also an increment of MDR. The response attenuation of narrow-band/long wave-length sensitive (NL)-cells was more variable, but their on-minus-off responses were also clearly reduced in the average during red surrounds. Blue surround illumination affected WL-cell responses little and less consistently than those of NL-cells, but often broadened the SRF also in the WL-cells towards shorter wavelengths. The M-cone excited and S-cone suppressed WM-cells were strongly suppressed by blue but only little affected by red surround illumination. The changes of spectral responsiveness came out clearly in the group averages of the different cell classes, but showed some variation between individual cells in each group. The zero-crossing wavelengths derived from on minus-off-responses were also characteristically shifted towards wavelengths complementary to those of the surround.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756833 TI - The squirrel monkey vestibulo-ocular reflex and adaptive plasticity in yaw, pitch, and roll. AB - The vestibulo-ocular reflex (VOR) was studied in adult squirrel monkeys before and after adaptation to magnifying and minifying viewing conditions. Monkeys were subjected to broadband (0.05-0.71 Hz) conditioning rotation for six hours in head yaw, pitch, and roll on separate occasions, and the VORs in these three planes were studied in darkness to assess adaptive plasticity in the reflexes. The gain of the horizontal VOR (H-VOR) averaged 0.8 across the frequency bandwidth studied (0.025-4 Hz). Phase was near 0 degrees from 4 to around 0.1 Hz, but developed a progressive lead as frequency declined further. Normal vertical VOR (V-VOR) gain climbed from 0.6 at 0.025 Hz to near 1 as frequency increased to 4 Hz. Phase lead was more pronounced at low frequencies than in the H-VOR. The normal torsional VOR (T-VOR) qualitatively resembled the V-VOR, showing similar phase but lower gains (0.3-0.7) across the frequency bandwidth. These findings suggest that the dynamics of the V-VOR and T-VOR resemble canal characteristics more closely than does the H-VOR. After adaptation to visual minification and conditioning rotation (0.5X for yaw and pitch, 0X for roll), gain decreased in each of the planes of conditioning. Similarly, gain increased in the plane of conditioning after adaptation to visual magnification (2X). The adaptive changes were greater at low (0.025-1 Hz) than at high (2.5-4 Hz) frequencies, and were more robust when gain was driven downward than upward. However, control (sham) adaptation experiments showed that VOR gain tended to drop slightly over 6 h in the absence of adaptive drive to do so, suggesting that the gain modifications may be more symmetric when referenced to the control. Adaptive VOR gain enhancement or decrement in the plane of conditioning did not result in systematic and parallel changes in orthogonal VOR planes. PMID- 1756834 TI - The primate vestibulo-ocular reflex during combined linear and angular head motion. AB - The squirrel monkey vestibulo-ocular reflex (VOR) was studied in darkness during Earth-horizontal rotation over a frequency range, 0.01-4 Hz, with the head positioned both centrally and displaced radially relative to the axis of rotation. With the head centered, the canal-mediated angular VOR (AVOR) was recorded in isolation. However, with the head placed eccentrically, otolith mediated linear VOR (LVOR) components interact with the AVOR to yield a combined AVOR-LVOR response. The plane of the ocular response could be manipulated by placing the head in different orientations relative to gravity (i.e. upright or nose-up). When the head was upright and centered, the horizontal AVOR was recorded. Comparisons between eye and head angular velocity showed that gain (pk eye/pk head velocity) was nearly flat, averaging 0.83, across the frequency range. Phase (difference in degrees between eye and head velocity, shifted 180 degrees by convention) was near 0 degrees, except at frequencies below 0.1 Hz where phase leads were seen. When the head was displaced eccentrically and in the nose-out position (facing away from the axis of rotation), gain rose above that of the AVOR alone. The enhancement was progressive with increasing frequency, but only for frequencies above 0.25 Hz. When the subject was turned nose-in, gain declined relative to the AVOR alone, and in a similar frequency-dependent fashion. These results are consistent with the notion that nose-out and nose-in responses to eccentric rotation represent a combined influence of the horizontal AVOR and LVOR, the latter driven by inter-aural tangential acceleration. To further evaluate this possibility, eccentric rotation was also used to assess the LVOR in isolation. With the head in the nose-up orientation, the AVOR was shifted into the head's roll plane and generated torsional ocular responses. With the head centered over the axis of rotation, no systematic horizontal responses were observed. However, when the head was displaced eccentrically and placed in the head-out and head-in positions, horizontal ocular responses were recorded which were proportional to head eccentricity and were of appropriate polarity to presume that they represented the inter-aural LVOR activated by inter-aural tangential acceleration. Response gain rose with increasing frequency, as did tangential acceleration. The LVOR in its resting state in darkness could be characterized by an average sensitivity of 40.3 degrees/s/g (g = 9.81 m/s2).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1756836 TI - Functional innervation of spinal cord tissue by fetal neocortical grafts in oculo: an electrophysiological study. AB - The ability of fetal neocortex transplants, to functionally innervate maturated cervical spinal cord grafts in oculo, was investigated in rats. We found that a neocortex co-graft will grow and develop in contact with a spinal cord graft, and will generate a functional input to maturated spinal cord tissue which can be activated by electrical stimulation of the neocortex graft. Our data suggest that orthodromic stimulation of this pathway causes short latency, transient excitations of spinal graft neurons. These appear to be mediated by an excitatory amino acid receptor since the response was noncompetitively antagonized by kynurenic acid. Kynurenic acid also noncompetitively antagonized the excitatory effects of glutamate superfused over single spinal cord grafts. The mechanism of the excitation probably does not involve an NMDA (N-methyl-D-aspartate) receptor since APV (2-amino-5-phosphonovalerate) did not alter the spinal graft neuronal responses to neocortical co-graft stimulation. These data suggest that fetal neocortex can functionally innervate maturated cervical spinal cord in the in oculo graft preparation. The in oculo spinal cord graft model may thus provide a unique test system for studies of the influence of drugs and other manipulations that might alter cortico-spinal pathway development as well as influence reestablishment of neuronal pathways after spinal cord injury. PMID- 1756835 TI - GABAergic interneurons and neuropil of the intralaminar thalamus: an immunohistochemical study in the rat and the cat, with notes in the monkey. AB - Immunohistochemistry using antibodies to glutamic acid decarboxylase (GAD) was used to investigate the intralaminar nuclei of the thalamus in rat, cat and monkey. Antibodies to gamma aminobutyric acid (GABA) were also used in the cat. Intralaminar immunoreactive cell bodies were not detected in the rat, but were clearly present in cat and monkey. In the latter species, GABA- or GAD immunopositive perikarya were distributed throughout the anterior intralaminar nuclei, whereas in the posterior intralaminar complex they prevailed in the lateral part of the centre median nucleus and around the fasciculus retroflexus. Measurements of the area of immunostained intralaminar cell bodies in cat and monkey indicated that they are represented by small neurons. Experiments in the cat, based on retrograde tracers injections involving large sectors of the frontal and parietal cortices and the head of the caudate nucleus, revealed that the GABA- or GAD-immunoreactive cells and the retrogradely labeled projection neurons represented two separate intralaminar cell populations, although the latter also included small cells. Considerable differences were observed in the immunoreactive GABAergic neuropil of the anterior and posterior intralaminar nuclei. Clusters of densely packed bouton-like immunoreactive elements were detected in the former structures in the rat, cat and monkey, and were especially evident in the central lateral nucleus; immunopositive varicose fibers and puncta were diffusely distributed in the posterior intralaminar structures. Taken together with data from the literature, the present findings indicate that in cat and monkey local circuit inhibitory cells regulate not only the activity of principal thalamic nuclei which project densely upon restricted cortical fields, but also of the intralaminar structures which are widely connected with the cerebral cortex and the striatum. Regional variations in the distribution of GABAergic fibers and terminals suggest major differences in the organization of inhibitory circuits and synaptic arrangements of the anterior and posterior intralaminar thalamus. PMID- 1756837 TI - Domiciliary nocturnal nasal intermittent positive pressure ventilation in COPD: mechanisms underlying changes in arterial blood gas tensions. AB - The improvement in arterial blood gas tensions following assisted ventilation in chronic obstructive pulmonary disease (COPD) has usually been attributed to the relief of incipient or established respiratory muscle fatigue. The contribution of changes in the load placed upon and the drive to the respiratory muscle pump have not been evaluated. We have investigated the contribution of changes in respiratory muscle strength, the ventilatory response to CO2 and ventilatory function to changes in arterial blood gas tensions in eight patients with severe COPD completing six months domiciliary nasal intermittent positive pressure ventilation. Six patients showed a reduction and two an increase in arterial carbon dioxide tension (PaCO2), median (range) for eight patients, -0.9 kPa (-1.5 to +0.4) (p less than 0.05) and seven showed an improvement in arterial oxygen tension (PaO2), +0.7 kPa (-0.4 to +1.7) (p less than 0.05) during daytime spontaneous breathing. The reduction in PaCO2 was not related to increased inspiratory muscle strength but was correlated with a decrease in gas trapping (Spearman rank correlation coefficient (r(S)) 0.85, p less than 0.05) and in the residual volume (r(s) 0.78, p less than 0.05), suggesting reduced small airway obstruction and, therefore, a reduction in load. The change in PaCO2 also correlated with the increase in ventilation at an end-tidal CO2 of 8 kPa during rebreathing (r(s) -0.76, p less than 0.05) suggesting improved chemosensitivity to CO2. Our data do not support the hypothesis that improvements were due to the relief of muscle fatigue. We suggest that the contribution of changes in load and central drive warrant further investigation. PMID- 1756838 TI - Does PEEP facilitate the resolution of extravascular lung water after experimental hydrostatic pulmonary oedema? AB - The effect of mechanical ventilation with positive end-expiratory pressure on the resolution of hydrostatic pulmonary oedema created by temporary left atrial balloon inflation was studied in mechanically ventilated dogs. Immediately after the hydrostatic process was terminated, by deflating the left atrial balloon, the animals were ventilated for 4 h with zero end-expiratory pressure (ZEEP, n = 6) or with a positive end-expiratory pressure (PEEP, n = 6) of 1.0 kPa (10 cmH2O). Gas exchange and extravascular lung water content (EVLW) with the double indicator dilution technique (dye/cold) were studied and gravimetric determination of lung water was made postmortem. EVLW decreased from 31.6 +/- 7.3 mean +/- SD ml.kg.1 during maximal oedema to 14.5 +/- 2.1 ml.kg.1 (p less than 0.001) 4 h after deflation of the left atrial balloon in dogs ventilated with ZEEP. The corresponding values in dogs ventilated with PEEP were a reduction in EVLW from 28.0 +/- 4.1 to 20.7 +/- 4.0 ml.kg.1 (p less than 0.01) (mean decrease 7.3 +/- 4.0 ml.kg.1). EVLW was significantly higher after 4 h on PEEP than after ZEEP (p less than 0.01). Gravimetric values at the end of the experiment were 12.4 +/- 2.8 ml.kg.1 (ZEEP) and 14.7 +/- 4.5 ml.kg.1 (PEEP) (NS). Oxygenation improved in both groups during the resolution of oedema with a more evident and early effect in the PEEP group. It is concluded that mechanical ventilation with PEEP of 1.0 kPa (10 cmH2O) in the resolution phase after experimental hydrostatic oedema improves oxygenation but retards the resolution of oedema. PMID- 1756839 TI - Thymoma: a clinicopathological comparative study of 25 cases. AB - We reviewed 25 patients with thymoma for clinical symptoms at presentation, X-ray findings and outcome. The tumours of all patients were classified using 3 different pathologic classification systems and each system was evaluated for its predictive power with respect to survival. The recent classification system by Muller-Hermelink allowed to distinguish thymomas with associated systemic syndromes from those without. However, no good prediction with respect to outcome could be made by any of the 3 systems. PMID- 1756840 TI - Toxic effects of oxygen on cultured alveolar epithelial cells, lung fibroblasts and alveolar macrophages. AB - Exposure to hyperoxia results in endothelial necrosis followed by type II cell proliferation. This suggests that type II cells are resistant to hyperoxia. Oxygen-induced lung injury may result from an overproduction of oxygen metabolites normally scavenged by antioxidants such as superoxide dismutase (SOD), glutathione peroxidase, catalase and reduced glutathione (GSH). Therefore, resistance of type II cells to hyperoxia may be linked to high antioxidant activities. To test this hypothesis we compared in vitro the effects of a 24 h exposure period to 95% O2 on cultured type II cells, lung fibroblasts and alveolar macrophages isolated from rats. We show that type II cells, when compared with other cell types, are highly sensitive to hyperoxia as shown by increased lactate dehydrogenase (LDH) release, decreased deoxyribose nucleic acid (DNA) and protein content of Petri dishes and decreased thymidine incorporation into DNA. Synthesis of dipalmitoylphosphatidylcholine was also significantly reduced. Antioxidant enzyme activities as well as glutathione content were not higher in type II cells than in other cell types. However, hyperoxia results in a decreased SOD activity and glutathione content in type II cells which was not observed in fibroblasts. We conclude that adaptative changes in SOD and glutathione metabolism could be important defence mechanisms in cells exposed to hyperoxia. PMID- 1756841 TI - Ventilatory function impairment and risk of cardiovascular death and of fatal or non-fatal myocardial infarction. AB - The relationship of ventilatory function to cardiovascular events was studied in 12,511 men and women, enrolled in 1976-1978 in a prospective population study. Until the end of 1983, 388 subjects died because of a cardiovascular disease, 133 died within 30 days of developing myocardial infarction (fatal myocardial infarction), while 238 had a non-fatal myocardial infarction. Cox proportional hazards models were employed for the analysis. In the models including tobacco smoking, cholesterol level, blood pressure, diabetes mellitus and body-mass index as covariates, forced expiratory volume in one second in percentage of predicted (FEV1% pred), forced vital capacity in percentage of predicted (FVC% pred), and the ratio between FEV1 and FVC (FEV1/FVC) were significantly related to the risk of cardiovascular death, e.g. compared with subjects with FEV1% pred or FVC% pred greater than or equal to 80 the risk of death from cardiovascular disease among subjects with FEV1% pred or FVC% pred less than 60 was approximately twice as high. There was a nonsignificant trend towards an increased risk of fatal myocardial infarction with reduction of FVC% pred, but in general the regression models did not show consistent relationship between lung function impairment and risk of myocardial infarction. In the regression models, which only included age and sex as covariates, reduced FVC% pred and FEV1% pred were significantly related to both cardiovascular mortality and to fatal myocardial infarction, but not to the non-fatal infarction, whereas the FEV1/FVC ratio was not related to fatal or to non-fatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756842 TI - Effect of nebulized salbutamol in preterm infants during the first year of life. AB - The acute effect on lung function of nebulized salbutamol and saline (placebo) has been investigated in preterm infants at follow-up. Twenty two premature infants, median gestational age 29 weeks (range 26-32 weeks) and birthweight 1,264 g (720-1,800 g), were studied at a median postnatal age of 7 months (range 6-9 months). Nine of the infants had recurrent respiratory symptoms; they coughed and/or wheezed at least 3 days per week for the previous 4 weeks. The remaining 13 infants were free from recurrent or persistent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured and specific airway conductance sGaw calculated before and 10 min after salbutamol and normal saline given via a nebulizer. Amongst the symptomatic infants administration of nebulized salbutamol was associated with a median reduction in Raw of 25% (p less than 0.01) and also a significant improvement in sGaw (p less than 0.01). In the asymptomatic infants neither Raw nor sGaw changed significantly. Nebulized saline caused no significant change in lung mechanics in either the symptomatic or asymptomatic infants. We conclude that nebulized salbutamol is an effective bronchodilator for symptomatic preterm infants less than one year of age. PMID- 1756843 TI - Sensitivity and specificity of the histamine challenge test for the diagnosis of asthma in an unselected sample of children and adolescents. AB - The purpose of this investigation was to study factors of importance for the degree of bronchial responsiveness and, furthermore, to evaluate the sensitivity, specificity and predictive value of a bronchial challenge test with histamine for the diagnosis of asthma in 495 randomly selected children and adolescents, aged 7 16 yrs, from Copenhagen, Rigshospitalet. Detailed history about allergic symptoms, physical examination and bronchial histamine challenge tests were performed at the out-patient clinic. Asthma, atopic disease and height were found to be of great importance for the degree of bronchial responsiveness, whereas the age, sex and smoking habits were of no significance. The percentage of asthmatics with bronchial hyperresponsiveness, i.e. sensitivity to the test, increased towards 100% on inhaling increasing concentrations of histamine, but this was accompanied by a decrease in specificity and predictive values of positive test in regard to the diagnosis of asthma. However, lower concentrations of histamine may be preferable in order to distinguish between asthma and non-asthma in population samples, as inhalation of 2.4 mg.ml-1 and provocative concentration producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) provided an acceptable sensitivity (57%), specificity (98%), and predictive value of a positive test (60%). We conclude that as regards the diagnosis of asthma, a low predictive value confirms that the bronchial challenge test plays only a supplementary, but valuable, role in detecting the disease in population samples. PMID- 1756844 TI - Inhaled budesonide in chronic bronchitis. Effects on respiratory impedance. AB - In a placebo controlled study the effects of 6 weeks' treatment with inhaled budesonide (1.6 mg daily) on the impedance of the respiratory system, spirometry and symptom scores were evaluated in 35 patients with chronic bronchitis with forced expiratory volume in one second (FEV1) greater than or equal to 70% predicted. Thirty patients completed the study. No statistically significant differences in the changes in morning peak expiratory flow rate (PEFR), symptom scores, use of terbutaline rescue medication and FEV1 were found between the placebo and the active treatment group. Budesonide treatment was found to result in a small decrease in resonant frequency and a less negative frequency dependence of resistance compared with the placebo group. PMID- 1756845 TI - Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment. AB - Gas exchange impairment and the development of atelectasis during enflurane anaesthesia were studied in 10 patients (mean age 70 yrs) with chronic obstructive pulmonary disease (COPD). Awake, no patient displayed atelectasis as assessed by computed X-ray tomography. The ventilation/perfusion distribution (VA/Q), studied by the multiple inert gas elimination technique, displayed an increased dispersion of VA/Q ratios (the logarithmic standard deviation of the perfusion distribution, mean log Q SD 0.99; upper 95% confidence limit of normal subject: 0.60), and increased perfusion of regions with low VA/Q ratios (0.005 less than VA/Q less than 0.1: 5.4% of cardiac output). Shunt was negligible (mean 0.6%). Computed chest tomography showed significantly larger cross-sectional thoracic areas than previously seen in subjects with healthy lungs (p less than 0.01). No atelectasis was seen in any patient. During anaesthesia there was a further worsening of the VA/Q mismatch with significantly increased log Q SD (1.29, p less than 0.05) but no increase in shunt (mean 1%). Minor atelectatic areas were noted in three patients, the others displayed no atelectasis at all. Chest dimensions were reduced by no more than 3% during anaesthesia, suggesting an unchanged or only minimally affected functional residual capacity. These findings contrast with those seen in patients with healthy lungs in whom atelectasis and shunt regularly develop during anaesthesia. PMID- 1756846 TI - Reversal of apnoea by aspiration reflex in anaesthetized cats. AB - Various flow and timing characteristics of breathing as well as electrocorticographic (ECoG) records were analysed in a model of reversible respiratory failure induced by N2 inhalation in 27 anaesthetized cats. During the first minute of respiratory arrest, nasopharyngeal stimulation by an elastic nylon fibre elicited a typical sniff- or gasp-like aspiration reflex (in 88.8% of cases), whilst similar tracheobronchial irritation evoked a weak cough reaction in one third of cases (34.2%). The aspiration reflex could also be evoked in progressive stages of apnoea characterized by very low and even isoelectric ECoG activity immediately before imminent irreversible respiratory failure, and it could interrupt and replace the periodic gasping sometimes occurring during apnoea. The reflex, comprising powerful inspiration efforts, could be evoked during apnoea many times in succession. Repeated aspiration reflexes alone resulted in recovery from hypoxic apnoea with gradual normalization of ECoG and subsequent restitution of spontaneous breathing even more frequently than it occurred in periodic gasping. Successful resuscitation from hypoxic apnoea by the aspiration reflex in cats suggests that nasopharyngeal stimulation can affect the mechanisms underlying the failure and restitution of breathing at least in some forms of apnoea. PMID- 1756847 TI - Inhaled clemastine, an H1 antihistamine inhibits airway narrowing caused by aerosols of non-isotonic saline. AB - Asthmatic subjects were challenged with aerosols of hyper- and hypotonic saline 15 min (Group A) and 90 min (Group B) after inhaling clemastine. Measurements were made of forced expiratory volume in one second (FEV1) before and after medication and after challenge. When the FEV1 values (% predicted) were compared on the active and placebo days they were higher 15 min after clemastine (p less than 0.05) for both challenges and higher 90 min after clemastine inhalation (p less than 0.05) for the hypertonic challenge. The % fall in FEV1 was compared after the same concentration of saline aerosol had been given on both active and placebo days. In Group A the % fall in FEV1 on the clemastine day was reduced after challenge with hypertonic (p less than 0.02) and hypotonic (p less than 0.03) aerosol. In Group B there was a reduction in the % fall in FEV1 on the clemastine day only after hypertonic challenge (p less than 0.04). The protective effect afforded by clemastine was unrelated to change in baseline lung function. We conclude that histamine is an important mediator of the airway response to non isotonic aerosols and suggest that the aerosol route of administration may be useful for delivering antihistamines. PMID- 1756848 TI - Lobar hypoplasia. AB - Lung tissue developmental abnormalities are seldom reported. According to the classification of Schneider (1900), which was amended by Boyden (1955), they include pulmonary agenesis, aplasia and hypoplasia. Due to the early onset of symptoms, lung agenesis and aplasia are usually detected soon after birth. Conversely, lung or lobar hypoplasia may remain clinically silent for a long time. A single case of left lower lobe hypoplasia is reported. A recurring and unrelenting septic fever was the presenting symptom, whilst the radiological picture showed a left lower lobe consolidation. On the surgical specimen gross pathology revealed a lobar hypoplasia. At a short-term follow-up (nine months) the patient shows good overall condition, being free from further complications. PMID- 1756849 TI - Occupational asthma to spores of Pleurotus cornucopiae. AB - We report the case of a young man who developed severe asthma a few months after starting work in a factory producing a single type of mushroom: Pleurotus cornucopiae (a basidiomycete). Immunological investigations, performed with material recovered from the filtering devices of the mushroom's bed, led to demonstration of specific IgE and IgG against spore extracts and to isolation of one discriminant antigen (molecular weight: 10.5 kd). Current data concerning the underestimated role of the basidiomycetes in allergic asthma are reviewed. PMID- 1756851 TI - Re. Calibration of peak expiratory flow (PEF) measuring devices. PMID- 1756850 TI - The aetiology of bronchial asthma and critical assessment of therapy. An international meeting on bronchial asthma Florence (Italy) March 7th-9th 1991. PMID- 1756852 TI - Are prions misfolded molecular chaperones? AB - A theory has been developed that could explain prion infection. Prions could be molecular chaperones that are required for their own assembly. The theory has been deduced from an analysis of protein folding and consequences explored by computer simulations. Thermo-kinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones. Consequently such a protein could behave as a new kind of informative molecule and replicate misfolding according to a process similar to infection. A quantitative model has been derived from this hypothesis that displays the characteristics of prion infections. This hypothesis satisfactorily explains the three manifestations - infection, familial and sporadic - that are the characteristic features of all prion diseases. PMID- 1756853 TI - Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. AB - Free fatty acids, natural uncouplers of oxidative phosphorylation, are shown to differ from artificial ones in that they fail to increase conductance of phospholipid bilayers which are permeable for the protonated form of fatty acids but impermeable for their anionic form. Recent studies have revealed that uncoupling by fatty acids in mitochondria is mediated by the ATP/ADP antiporter and, in brown fat, by thermogenin which is structurally very similar to the antiporter. It is suggested that both the ATP/ADP antiporter and thermogenin facilitate translocation of the fatty anions through the mitochondrial membrane. PMID- 1756854 TI - Structure-function relationships of hirulog peptide interactions with thrombin. AB - Using hirudin as a model, a novel class of bivalent thrombin inhibitors has been designed and characterized (Maraganore et al. (1990) Biochemistry 29, 7095-7101). These peptides, designated 'hirulogs', interact with both thrombin's catalytic center and its anion-binding exosite for fibrinogen recognition. In order to investigate structure-activity relationships in hirulog peptides, a number of peptide and peptidomimetic derivatives with alterations in catalytic-site binding and anion-binding exosite binding moieties were prepared. Replacements or modifications in the catalytic site and exosite binding moieties were achieved with the consequences of maintaining or improving antithrombin activity. In addition to showing improved affinity for thrombin, some derivatives with Ki's in the sub-nanomolar range showed increased anticoagulant activities. These findings highlight the versatility of hirulog peptides in their bivalent interactions with thrombin. PMID- 1756855 TI - Interaction of intact type VI collagen with hyaluronan. AB - The capacity of non-pepsinyzed type VI collagen to bind to hyaluronan was investigated. Type VI collagen was extracted from bovine meniscal cartilage with 6 M GuHCl and purified by extraction of PEG precipitates and dissociative Sephacryl S-500 HR chromatography. Type VI collagen, detected with a monoclonal antibody, bound in 0.5 M NaCl to hyaluronan-coated micro-wells, the degree of binding being higher at 37 degrees C than 23 degrees C and 4 degrees C. Incubation of type VI collagen in competitive inhibition assays with testicular hyaluronidase digests of hyaluronan in liquid phase, reduced binding of the protein to hyaluronan-coated microwells to background levels. Thus, non pepsinyzed type VI collagen binds to hyaluronan in vitro. PMID- 1756856 TI - Receptor-mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids. AB - Membrane-bound peptidases are critical regulators of peptide hormones. We therefore characterized aminopeptidase A (APA) activity in human glomerular epithelial cells (HGEC) and studied the control of its expression. APA, which splits off the N-terminal Asp from angiotensin II (AII), was present at the surface of HGECs (55% of the total enzyme). APA activity was calcium-dependent and was inhibited by amastatin. Treatment of HGECs by dexamethasone (DEX) increased ecto-APA activity in a dose- and time-dependent manner. Maximal increase of APA activity (x 2) occurred after treatment with 0.5 microM DEX for 5 days. HIgher concentrations (1-10 microM) of aldosterone (ALD) stimulated APA activity to a lesser extent (x 1.25). Actinomycin D and cycloheximide prevented and RU 38486, a glucocorticoid receptor antagonist, suppressed the DEX-induced increase in APA activity. These results indicate that AII availability at glomerular receptor sites may be reduced by DEX and suggest a role for glucocorticoids in AII-dependent changes of glomerular filtration rate. PMID- 1756857 TI - Characterization of trypsinogens 1 and 2 in two human pancreatic adenocarcinoma cell lines; CFPAC-1 and CAPAN-1. AB - Proteins with trypsin-like immunoreactivity (first detected by a specific immunoenzymatic assay) were isolated from CAPAN-1 and CFPAC-1 cell culture conditioned media by chromatography on an immunoadsorbent prepared with a polyclonal antibody directed against trypsin 1. The adsorbed proteins were devoid of free trypsin activity but trypsin activity was present after enterokinase activation demonstrating that the immunoreactive trypsin present in cell supernatants corresponds to trypsinogens. When characterised by Western blotting using a monoclonal antibody directed against human trypsin 1 two protein bands corresponding to trypsinogen 1 (23 kDa) and trypsinogen 2 (25 kDa) gave a positive reaction. These results demonstrate the presence of trypsinogens 1 and 2 in CAPAN-1 and CFPAC-1 cells and in their culture-conditioned media. PMID- 1756858 TI - Determination of the amino acid sequence of an intramolecular disulfide linkage containing sperm-activating peptide by tandem mass spectrometry. AB - A sperm-activating peptide (SAP) was isolated from the egg jelly of the sea urchin Stomopneustes variolaris. The presence of an intramolecular disulfide linkage in the peptide was demonstrated by fast atom bombardment (FAB) mass spectrometry with the intact and reduced peptides. The amino acid sequence of the reduced peptide was determined to be Lys-Phe-Cys-Pro-Glu-Gly-Lys-Cys-Val by tandem mass spectrometry from the spectrum produced by a collision-induced decomposition method. Furthermore, it was also demonstrated that SAPs obtained from sea urchins Arbacia punctulata and Glyptocidaris crenularis are cyclic peptides containing one cystine residue by FAB mass spectrometry. PMID- 1756859 TI - Structure/function relationships in the inhibition of thimet oligopeptidase by carboxyphenylpropyl-peptides. AB - Some novel N-[1(RS)-carboxy-3-phenylpropyl]tripeptide p-aminobenzoates have been synthesised as inhibitors of thimet oligopeptidase (EC 3.4.24.15). These compounds are considered to bind as substrate analogues with the Cpp group in S1 and the peptide portion in the S' sites. The most potent inhibitor is Cpp-Ala-Pro Phe-pAb, which has a Ki = 7 nM. Substitution of Gly for Ala at P1' leads to weaker binding which can be ascribed to increased rotational freedom. Good substrates often have Pro at P2' and Pro is favoured over Ala at this position in the inhibitors, too. When P2' is Pro, Phe is preferred over Tyr and Trp in P3'. The p-aminobenzoate group makes an important contribution to the binding, probably by forming a salt bridge, and removal of the C-terminal negative charge results in much less potent inhibitors. PMID- 1756860 TI - Identification of amino acid residues of Ras protein that are essential for signal-transducing activity but not for enhancement of GTPase activity by GAP. AB - To determine the amino acid residues required for the signal-transducing activity of the human c-Ha-Ras protein, we introduced point mutations at residues 45-54 near the 'effector region' (residues 32-40). We transfected PC12 cells with these mutant genes and also micro-injected the mutant proteins, bound with an unhydrolyzable GTP analog, into PC12 cells. Both procedures showed that Val45--- Glu and Gly48----Cys mutations impaired the ability of the Ras protein to induce morphological change of PC12 cells. These mutations did not affect the guanine nucleotide-binding activity or GTPase activity in the absence or presence of bovine GTPase-activating protein (GAP). Therefore, the Val45 and Gly48 residues should be included by definition in the effector region responsible for the signal transduction, while only a subset of the effector-region residues is required for enhancement of the GTPase activity by GAP. PMID- 1756861 TI - Functional significance of aromatic amino acids from three peptide loops of the alpha 7 neuronal nicotinic receptor site investigated by site-directed mutagenesis. AB - Three aromatic amino acids, Tyr92, Trp148 and Tyr187 belonging to three separate domains of the alpha 7-subunit of neuronal nicotinic acetylcholine receptor were mutated to phenylalanine, and the electrophysiological response of the resulting mutant receptors analyzed in the Xenopus oocyte expression system. All mutations significantly decreased the apparent affinities for acetylcholine and nicotine, and to a lesser extent, those for the competitive antagonists dihydro-beta erythroidine and alpha-bungarotoxin. Other properties investigated, such as the voltage dependency of the ion response as well as its sensitivity to the open channel blocker QX222, were not significantly changed, indicating that the mutations affected selectively the recognition of cholinergic ligands by the receptor protein. The maximal rates for the rapid desensitization process were slightly modified, suggesting that the contribution of Tyr92, Trp148 and Tyr187 to the binding area might differ in the various conformations of the nicotinic receptor. Other mutations at nearby positions (S94N, W153F, G151D and G82E) did not affect the properties of the electrophysiological response. These data point to the functional significance of Tyr92, Trp148 and Tyr187 in the binding of cholinergic ligands and ion channel activation of the nicotinic receptor, thus supporting a multiple loop model [(1990) J. Biol. Chem. 265, 10430-10437] for the ligand binding area. PMID- 1756862 TI - Plant basic 7 S globulin-like proteins have insulin and insulin-like growth factor binding activity. AB - Basic 7 S globulin (Bg) is a cysteine-rich glycoprotein present in soybean seeds. Mature Bg is composed of high- and low-kDa subunits linked by disulfide bonding. A ligand blotting experiment using [125I]insulin and [125I]insulin-like growth factor-I and -II showed that Bg subunits are able to bind not only to insulin but to insulin-like growth factors-I and -II. Bg-like proteins from other legume species cross-reacted with anti-Bg antibody also bind to insulin and insulin-like growth factors. Bg-like protein in carrot cells was found to have insulin binding activity. Bg-like proteins may be involved in an insulin-like regulatory mechanism in many plant species. PMID- 1756863 TI - A Lys27-to-Glu27 mutation in the human insulin-like growth factor-1 prevents disulfide linked dimerization and allows secretion of BiP when expressed in yeast. AB - Recombinant human insulin-like growth factor-1 (IGF1) secreted from yeast contains only 10-15% of the active monomer. A majority of the IGF1-like molecules are disulfide bonded dimers. These dimers are not formed in an IGF1 mutant where Lys27 has been replaced by glutamic acid. However, increased levels of secreted BiP (the yeast KAR2 gene product) are seen in cells expressing the mutant. These results imply that by preventing ionic interactions between two IGF1 molecules, intermolecular disulfide bonds do not form in yeast, and that in the mutant there is a structural change which induces BiP, allowing its secretion. PMID- 1756864 TI - 2-Deoxy-2-fluoro-D-galactose protein N-glycosylation. AB - 2-Deoxy-2-fluoro-D-galactose (dGalF), added to the medium of primary cultured rat hepatocytes, inhibited N-glycosylation of membrane (gp 120) and secretory glycoproteins (alpha 1-macroglobulin) in a concentration-dependent manner. Complete inhibition of N-glycosylation was achieved at concentrations of 1 mM and above. At identical concentrations, 2-deoxy-2-fluoro-D-glucose (dGlcF) caused only incomplete inhibition of N-glycosylation. dGalF reduced incorporation of D [2,6-3H]mannose into lipid-linked oligosaccharides indicating interference with their assembly in the dolichol cycle. PMID- 1756865 TI - Evidence for a Competitive-Displacement Model for the initiation of protein synthesis involving the intermolecular hybridization of 5 S rRNA, 18 S rRNA and mRNA. AB - We have previously shown that a 5'-terminal region of mouse 5 S rRNA can base pair in vitro with two distinct regions of 18 S rRNA. Further analysis reveals that these 5 S rRNA-complementary sequences in 18 S rRNA also exhibit complementarity to the Kozak consensus sequence surrounding the mRNA translational start site. To test the possibility that these 2 regions in 18 S rRNA may be involved in mRNA binding and translational initiation, we have tested, using an in vitro translation system, the effects of DNA oligonucleotides complementary to these 18 S rRNA sequences on protein synthesis. Results show that an oligonucleotide complementary to one 18 S rRNA region does inhibit translation at the step of initiation. We propose a Competitive-Displacement Model for the initiation of translation involving the intermolecular base-pairing of 5 S rRNA, 18 S rRNA and mRNA. PMID- 1756866 TI - Trimeric G-proteins of the trans-Golgi network are involved in the formation of constitutive secretory vesicles and immature secretory granules. AB - Non-hydrolysable analogues of GTP, such as GTP gamma S and GMP-PNP, have previously been shown to inhibit the formation of constitutive secretory vesicles (CSVs) and immature secretory granules (ISGs) from the trans-Golgi network (TGN). Using a cell-free system, we show here that the formation of these vesicles is also inhibited by [A1F4]-, a compound known to act on trimeric G-proteins. Addition of highly purified G-protein beta gamma subunits stimulated, in a differential manner, the cell-free formation of both CSVs and ISGs. ADP ribosylation experiments revealed the presence of a pertussis toxin-sensitive G protein alpha subunit in the TGN. We conclude that trimeric G-proteins regulate the formation of secretory vesicles from the TGN. PMID- 1756867 TI - Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2. AB - The extracellular form of 14-kDa group II phospholipase A2 has been found to accumulate at various types of inflammatory sites. In the present paper, we have studied the possible role of the extracellular 14-kDa group II phospholipase A2 in the process of prostaglandin production in activated rat mast cells. When mast cells obtained from the peritoneal cavity of rats were sensitized with IgE, challenged with antigen and then exposed to extracellular 14-kDa group II phospholipase A2, appreciable release of prostaglandin D2 was observed. Generation of prostaglandin D2 was dependent on the concentration of the phospholipase A2 as well as that of the antigen, while no appreciable prostaglandin D2 generation was observed with cells in the absence of the antigen. No histamine release was observed under the same conditions. Phosphatidylcholine in mast cell membranes was appreciably hydrolyzed to liberate free arachidonic acid when mast cells were incubated with 14-kDa group II phospholipase A2 added exogenously in the presence of the antigen. Both the generation of prostaglandin D2 and the release of arachidonic acid were retarded by inhibitors specific to 14-kDa group II phospholipase A2. Thus, 14-kDa group II phospholipase A2 may function in the process of inflammation by acting on IgE antigen-primed mast cells, which are not fully activated, to generate eicosanoids. PMID- 1756868 TI - Phorbol ester stimulation of pancreatic beta-cell replication, polyamine content and insulin secretion. AB - Long-term effects of the protein kinase C activating phorbol ester, TPA, on pancreatic beta-cell proliferation and insulin production were investigated. It was found that beta-cell replication and long-term insulin secretion were enhanced in TPA-treated islets. This was not accompanied by a corresponding increase in (pro)insulin biosynthesis, presumably contributing to the lowered islet insulin content. TPA also increased islet polyamine content but when this increase was prevented by blocking polyamine synthesis, DNA replication and insulin secretion remained elevated. These findings indicate that TPA stimulates beta-cell replication and insulin secretion and suggest a stimulatory role for protein kinase C, but not for polyamines, in these processes. PMID- 1756869 TI - Rapid turnover of low density lipoprotein receptor in human monocytic THP-1 cells. AB - We examined whether human monocyte-derived macrophages had low density lipoprotein (LDL) receptors with a short life span. The human monocytic leukemia cell line, THP-1, was highly differentiated when treated with phorbol ester. LDL receptors degraded rapidly with half-lives of 3-4 h in THP-1 cells before phorbol ester treatment. During the transition into monocytic cells, expression of the LDL receptor gene was not affected. However, relative degradation rates of LDL receptors normalized by those of cellular total proteins were about twice as fast in phorbol ester-treated THP-1 cells compared to untreated cells. PMID- 1756870 TI - Glycinebetaine enhances and stabilizes the evolution of oxygen and the synthesis of ATP by cyanobacterial thylakoid membranes. AB - Glycinebetaine (betaine), an osmoregulant in halophilic plants, stabilized the evolution of oxygen and the synthesis of ATP by thylakoid membranes from the cyanobacterium Synechocystis PCC6803 when it was present during the preparation and incubation of the thylakoid membranes. Moreover, betaine enhanced the evolution of oxygen and the synthesis of ATP when present during assays. When betaine at 1.0 M was present during the preparation of thylakoid membranes and during the measurement of activity, the rate of evolution of oxygen was equivalent to that of intact cells. PMID- 1756871 TI - The sexual inducer of Volvox carteri. Its large-scale production and secretion by Saccharomyces cerevisiae. AB - The DNA sequence coding for the sexual inducer glycoprotein of Volvox carteri and its N-terminal signal peptide was placed under the control of the repressible acid phosphatase promoter of the yeast Saccharomyces cerevisiae in a yeast-E. coli shuttle vector. Yeast transformed by this construct synthesized and secreted into the culture medium biologically active inducer in amounts two to three orders of magnitude higher than observed in the Volvox system. PMID- 1756872 TI - The major endogenous bovine brain protein kinase C inhibitor is a heat-labile protein. AB - A crude cytosolic fraction prepared from bovine brain contained protein kinase C, as shown by immunoblotting, but its activity was undetectable, suggesting the presence of interfering factors. Phosphatase, ATPase and protease activities did not account for the absence of detectable protein kinase C activity. The major contributing factor was found to be a heat-labile protein which was separated from the kinase by ion-exchange chromatography. The contribution to the total inhibitory activity of heat-stable proteins was relatively minor, suggesting that they may not function physiologically as protein kinase C inhibitors. PMID- 1756873 TI - Femoro-distal grafts--can the results be improved? PMID- 1756874 TI - Selection of amputation level: a review. AB - Preservation of the knee joint in a patient undergoing lower limb amputation for critical ischaemia is associated with improved postoperative rehabilitation and mobility. Yet, for most surgeons the below-knee to above-knee amputation ratio remains less than one. Poor wound healing and a high reamputation rate for below knee stumps are important factors mitigating against below-knee amputations. Many tests (Doppler indices, segmental pressures, skin blood flow, skin perfusion pressure, TcpO2, thermography) have been described to predict the likelihood of successful healing of an amputation stump but none appears to have gained widespread acceptance. Clinical judgement alone is insufficient to predict the success or failure of an amputation stump. In this review, we have looked at the evidence in support of these tests, particularly those routinely available to most surgeons. PMID- 1756875 TI - Pedal reconstructions for limb salvage. AB - If only one pedal artery is patent the vascular surgeon has to decide between primary amputation and a bypass. Between 1980 and 1990, 460 femoro-distal bypasses were performed in our clinic and 8% (39 cases) of these received a pedal reconstruction. At discharge from the hospital 85% of these grafts were patent. The primary goal of treatment, to maintain life and salvage the limb on the basis of a functioning bypass, was obtained in 82% of patients. After 1 year the secondary patency of our pedal reconstructions was 68%. Taking the mortality of amputations into account, vascular surgery to the foot arteries is preferable to amputation, whenever possible. PMID- 1756876 TI - The clinical use of an antibiotic-bonded graft. AB - Attempts to produce an antibiotic-bonded prosthesis have failed owing to poor binding, drug toxicity or inadequate antimicrobial activity of the antibiotic particularly against Staphylococcus epidermidis. Rifampicin, with an ideal spectrum, but untested against slime-forming S. epidermidis has recently been shown to bind with carboxyl groups on gelatin-sealed Dacron. We therefore investigated rifampicin activity against 30 slime-forming adherent S. epidermidis colonies, isolated from 40 consecutive aortic graft recipients, and compared it with their methicillin, gentamicin, cefuroxime, tetracycline and vancomycin resistance patterns. The S. epidermidis colonies were highly sensitive to very low levels of rifampicin. Rifampicin was then bonded to gelatin-sealed Dacron aortic prostheses which were inserted in four patients at high risk of developing subsequent infection. PMID- 1756877 TI - The value of duplex scanning with venous occlusion in the preoperative prediction of femoro-distal vein bypass graft diameter. AB - The diameter of the long saphenous vein has been shown to affect the outcome of femoro-distal bypass. Many surgeons regard a vein with a diameter of less than 3 mm as being unsuitable. The long saphenous vein was studied in 35 patients undergoing femoro-distal bypass. Diameter measurements of the vein were performed using an ATL duplex scanner at the groin, mid-thigh and knee. Measurements were performed preoperatively both at rest and with a venous occlusion cuff to dilate the vein, and subsequently at 7 days and 2 months after implantation. The mean diameter of the vein at the mid-thigh was 4.1 mm non-dilated, 5.1 mm with occlusion, 5.0 mm 7 days postoperatively and 5.2 mm at 2 months (ANOVA, p less than 0.05). The mean diameter of the vein at the knee was 3.9 mm non-dilated, 4.8 mm with occlusion, 4.8 mm at 7 days and 4.9 mm at 2 months after operation (ANOVA, p less than 0.025). In all five patients whose preoperative resting vein diameter at the knee or mid-thigh was less than 3 mm, preoperative dilatation occurred, such that the diameter became greater than 3 mm. These results suggest that by using a technique of venous occlusion at the time of pre-operative vein mapping, the functional diameter of the vein can be predicted and vein utilisation may be increased. PMID- 1756878 TI - Is laser assisted angioplasty a real alternative to surgical treatment of occluded peripheral vessels? AB - Since 1988 250 patients had occluded peripheral arteries reopened by an Argon laser. The mean age of the 110 men and 85 women was 71 years and the mean length of all occlusions 13.4 cm. The primary success rate was 81.5% with a perforation rate of less than 2%. The patency rate after 96 weeks was 80%. PMID- 1756879 TI - C-reactive protein and alpha 1-acid glycoprotein in monitoring of patients with acute arterial occlusion. AB - C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP) levels were studied in sera of 75 patients with acute arterial occlusion. Depending on the degree of ischaemia, patients were divided into two groups: grade I--26 patients--and grade II--49 patients. All patients were treated surgically; 42 embolectomies, 17 endarterectomies and 16 bypasses were performed. After surgery in 19 patients various complications were observed. The concentration of both proteins at the time of admission was higher in the serum of patients with grade II than with grade I ischaemia. Similarly the concentration of both proteins was significantly higher in the sera of the patients admitted after 8 h than in patients admitted within 8 h of the onset of ischaemia. CRP and AGP levels were significantly higher in the serum of patients with ischaemia of the lower limb than in those with ischaemia of the upper limb. In all patients 2-3 days after surgery a significant increase in serum CRP and AGP was observed. In uncomplicated cases on days 7-10 the values of both proteins decreased below the level observed at the time of admission. However, in patients who experienced postoperative complications high levels of both serum proteins (especially CRP) were found on days 7-10. Complications were detected with a sensitivity and specificity of 84 and 95%, respectively, using a CRP level of 49 mg l-1 as the cut-off point. PMID- 1756880 TI - Monitoring of somatosensory evoked potentials during carotid endarterectomy: relationship with different haemodynamic parameters and clinical outcome. AB - The authors studied the changes of Somatosensory Evoked Potentials (SEPs) performed in 241 anaesthetised patients during 264 carotid endarterectomies (CEs). SEP responses were considered significantly modified when the central conduction time was greater than 1 ms and/or when the amplitude of the complex N20-P25 decreased by at least 50%. Both CCT and N20-P25 have been correlated with different parameters, including the presence or absence of preoperative neurological deficits, the type of general anaesthesia, the status of the contralateral and the ipsilateral carotid artery, stump pressure, the use of an intraluminal shunt and the perioperative results. After carotid cross-clamping SEP responses were within the normal range in 236 CEs (89%), and abnormal in 28 (11%). A shunt was inserted 23 times in 264 (9%) cases. None of the patients operated on in this series experienced a permanent neurological deficit; there were three (1.1%) transient deficits (two Rinds and one TIA) and two deaths from non-neurological causes. Only one of the transient deficits was present when the patient woke from the anaesthetic and this event was predicted by significant modification of the SEP which did not reverse after removal of the clamps (a shunt was not used). None of the patients in our series who did not present significant modifications of SEPs during the operation had any postoperative neurological deficit. The authors conclude that SEP recording is a highly reliable and objective method for continuous monitoring of brain function during CE. PMID- 1756881 TI - Transmetatarsal amputation in patients with peripheral vascular disease. AB - Transmetatarsal amputation has the reputation of being an operation with a poor healing rate, and less than a 50% success rate had recently been reported. The outcome of this amputation in patients with peripheral vascular disease has been retrospectively studied in this paper by examining 34 transmetatarsal amputations performed over a 5-year period. Twelve patients had had previous toe amputations and 22 were diabetic with an overall healing rate of 68%. There was no significant difference in the success rate between diabetics and non-diabetics. One patient died in the postoperative period, giving an early post-operative mortality of 3%. Revision of failed transmetatarsal below-knee amputation resulted in healing in seven patients out of nine, suggesting that it does not compromise later amputation at a higher level. Healing did not appear to be influenced by factors such as sympathectomy, previous arterial reconstruction or peripheral pulses. Transmetatarsal amputation provides patients who have a short life expectancy with a durable functional stump which is prosthesis free. PMID- 1756882 TI - Changes in middle cerebral artery flow velocity and pulsatility index after carotid endarterectomy. AB - Transcranial Doppler sonography (TCD) was used in 33 patients undergoing carotid endarterectomy (CEA). Mean flow velocity (MCA MV) and the pulsatility index in the middle cerebral artery (MCA PI) were measured pre- and on six occasions postoperatively. The MCA MV was reduced by anaesthesia but was increased postoperatively (+43%, p less than 0.001) compared to the preoperative value and was still increased at late follow-up after several months. The MCA PI, which was lower preoperatively than normally reported in this age group, was not changed by anaesthesia but then rose and remained elevated, i.e. within normal limits 72 h postoperatively (+30%, p less than 0.01) as well as at late follow-up. No significant changes in MCA MV or MCA PI were noted on the contralateral side. The results from this study support earlier findings from invasive studies showing that CEA results in an increased flow in the middle cerebral artery on the operated side and an increased MCA PI suggests an increased resistance on the operated side. The findings are compatible with an increased cerebral blood flow during the first days after CEA and with the operated side supplying a greater part of the cerebral blood flow even several months after surgery. PMID- 1756883 TI - Intensive care after abdominal aortic surgery. AB - This study examined the necessity for an intensive care environment after abdominal aortic surgery. The detailed records of 45 consecutive patients were reviewed for the first 48 h after operation, recording the occurrence and numbers of episodes of defined medical events or prescription of non-routine drugs. Medical events were hypertension (greater than 200 mmHg), hypotension (less than 100 mmHg), obliguria (less than 20 ml/h) and pulmonary problems. Thirty-six patients (80%) had medical events (hypertension 20, hypotension 17, oliguria 31, hypoxia 10, chest complications 12), and 38 (84%) had medical interventions. Only two had no events or interventions. Twenty-seven (59%) had more than one episode of a medical event which would not have been predicated from their preoperative state. There were three deaths (mortality 6.7%). These results support the case for intensive monitoring and immediate access to experienced medical advice for these patients. In hospitals where the intensive care unit is the best place to provide these facilities, elective operation may need to be deferred if an intensive care bed is not available. PMID- 1756884 TI - Hyperbaric oxygen therapy for ischaemia of the hand due to intra-arterial injection of methadone and flunitrazepam. AB - We present a case of accidental injection of oral methadone and flunitrazepam into the ulnar artery, with resultant severe ischaemia of the hand. Initial therapy consisted of systemic vasodilators, low molecular weight dextran and aspirin. When this therapy failed to produce improvement and amputation of the involved hand seemed inevitable, the patient was referred for hyperbaric oxygen (HBO) therapy. In spite of a 12 day delay in the initiation of HBO, the response was dramatic, with almost complete resolution of the ischaemic signs and symptoms. Intra-arterial injection, which is only rarely encountered in drug addicts, frequently results in severe ischaemia of an extremity, and carries with it a poor prognosis with currently accepted therapy. Given the presently reported experience and the known physiology of HBO, we conclude that HBO should be started early in the treatment of intra-arterial injection of drugs, and should also be considered following prolonged delays. PMID- 1756885 TI - Tunnelling instruments for vascular grafts: problems and solutions. AB - When autologous veins or vascular prostheses are implanted for bypass operations or haemodialysis, the use of an appropriate tunnelling device is extremely helpful. In order to avoid perigraft haemorrhage and allow undelayed graft incorporation, the tunneller should match the diameter of the implant. Interchangeable shafts of various lengths and blunt tips of various diameters are prerequisites for a versatile instrument. Most instruments on the market have an important drawback: the handle is welded to one end of the shaft thus preventing "bi-directional" use. We have therefore developed a modified tunneller that can be used equally well in either direction. The connection between shaft and handle affords torsional rigidity and thus allows precise guidance during insertion. The handle can be attached to both ends of the shaft. Thus, for example, in a femoro popliteal bypass, the distal anastomosis can be constructed first, followed by the introduction of the tunneller from the knee to the groin. As a next step the tip and handle are interchanged and the graft is passed from the knee to the groin. When a haemodialysis shunt with a PTFE-loop is inserted, the bidirectional use of the tunneller makes it possible to insert the graft with a smooth curve into the smallest possible cavity. Thus, the new instrument set called the "Bi directional Tunneller" is more versatile and easier to use than other tunnellers presently available. PMID- 1756886 TI - False aneurysm of the abdominal aorta after blunt trauma. AB - Injuries of the abdominal aorta due to blunt trauma are rare. So far, 33 cases have been reported in the English literature and false aneurysm formation after such injuries is even rarer. In this article, a case of false aneurysm of the abdominal aorta after blunt trauma in an acrobat which was successfully managed is reported, and the English literature for similar cases reviewed. PMID- 1756887 TI - Chylous ascites following aneurysm surgery. AB - A case of chylous ascites occurring after elective abdominal aortic aneurysm repair is described. The patient was initially managed conservatively with hyperalimentation and intermittent drainage of the retroperitoneal collection, but, this proved inadequate and a peritoneo-venous shunt was inserted. Although the shunt appeared to work well the patient finally died of septicaemia. PMID- 1756889 TI - Leaking abdominal aortic aneurysm presenting as an inguinal mass. AB - Two patients with leaking abdominal aortic aneurysm (AAA) presenting as a tender inguinal mass are reported. Unusual presentations such as this often cause delays in definitive surgery which result in increased morbidity and mortality. It follows that the diagnosis of a leaking AAA should be considered in all patients with a tender pulsatile abdominal mass regardless of the presentation. PMID- 1756888 TI - Late false aneurysm formation along an axillobifemoral graft. AB - False aneurysm formation is a rare complication of prosthetic arterial reconstruction other than at the anastamosis. Several aetiological mechanisms have been postulated. We report the development of a false aneurysm along the course of a prosthetic graft, with local communication between aneurysm and graft at more than one site. Possible causes of this type of graft failure are discussed. PMID- 1756890 TI - Popliteal vein aneurysm. PMID- 1756891 TI - Diagnosis and management of sleep disorders. PMID- 1756892 TI - Persistent/recurrent pneumonia in infants and children. AB - An infant or child with recurrent/persistent pneumonia requires a careful evaluation to determine if an underlaying condition may be treatable or surgically correctable. PMID- 1756893 TI - Brown-Sequard syndrome following cervical spine compression fracture. AB - Brown-Sequard Syndrome is most commonly caused by penetrating trauma to the spinal cord. The case of a 15-year-old male who developed Brown-Sequard Syndrome following blunt cervical spine trauma sustained in an automobile accident is presented. Brown-Sequard Syndrome is rarely seen following blunt trauma; however, one must be suspicious so as not to overlook this type of lesion. PMID- 1756894 TI - The value of cluster and environmentally related cancer studies in Delaware. PMID- 1756895 TI - Fraud and abuse safe harbor regulations. PMID- 1756896 TI - Help for the busy doctor. PMID- 1756897 TI - The pancreatic islet as Rubik's Cube. Is phospholipid hydrolysis a piece of the puzzle? AB - At least three types of phospholipase exist in the beta-cells of the pancreatic islet. Data regarding their physiological activation are incomplete but suggest that glucose (or its metabolite glyceraldehyde) either activates or potentiates the activation of several phospholipases. At least seven phospholipid hydrolysis by-products (diacylglycerol, myo-inositol 1,4,5-trisphosphate, lysophospholipids, arachidonic acid and its cyclooxygenase- and lipoxygenase-derived metabolites, phosphatidate) have been demonstrated to have effects compatible with their postulated roles as mediators or modulators of islet function. Presumptive mechanisms of action have been tentatively identified for these metabolites. However, key studies in the puzzle are missing, and current methodologies have important limitations. Shortcomings include the paucity of measurements of the mass of metabolites; the frequent use of static incubations rather than perfusions; a lack of complete time- and agonist concentration-dependence curves; the equation of metabolite accumulation with rates of metabolite generation (which ignores metabolite removal as a key variable); the use of nonspecific, insensitive, or ambiguous phospholipase assays; and the need for more studies directly correlating lipid metabolism and insulin secretion in physiologically functioning preparations. Like Rubik's Cube, the pancreatic islet is a dynamic puzzle comprised of many interrelated components requiring proper alignment and integration. Phospholipid turnover is one "panel" in the islet; however, an obligate role for phospholipase activation in glucose-induced insulin secretion is not yet rigorously established, despite tantalizing, inferential evidence. It may be that glucose serves principally to potentiate the phospholipase and secretory responses to other signals that act by initiating phospholipid hydrolysis. PMID- 1756898 TI - Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats. AB - We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756899 TI - T-lymphocyte-receptor repertoire of infiltrating T lymphocytes into NOD mouse pancreas. AB - This study analyzed T-lymphocyte-receptor V beta genes of infiltrating lymphocytes into the pancreases of 12- to 16-wk-old NOD mice with severe insulitis and 5-wk-old mice with mild insulitis by the quantitative polymerase chain reaction method. The V beta transcripts on infiltrating T lymphocytes into pancreases with severe insulitis in older NOD mice were diverse. In contrast, the V beta 11 gene transcript was predominantly expressed on T lymphocytes in the pancreas in younger NOD mice with mild insulitis, suggesting the possible role of V beta 11+ T lymphocytes in triggering insulitis in this species. PMID- 1756900 TI - Effects of tryptophan on depression and aggression in STZ-D mice. AB - Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in STZ-administered male National Institutes of Health Swiss mice. In addition, the effect of tryptophan on behavior in the resident-intruder test of aggression was studied. Tryptophan is effective in the treatment of mild depression and may reduce aggressive behavior. Diabetes was induced with injection of 200 mg/kg body wt i.p. STZ. Two weeks after STZ treatment, the mice received 0, 50, and 100 mg/kg i.p. tryptophan 60 min before the swim test. The STZ-administered mice exhibited lengthened immobility in the swim test, and tryptophan caused a dose related shortening in their immobility times. The control and STZ mice, which were isolated for 1 wk before the resident-intruder test, did not show any difference in the time spent in social investigation or aggressive or defensive behaviors. However, 100 mg/kg i.p. tryptophan 60 min before the test reduced the social interaction and aggressive behavior of the STZ-D mice but increased these behaviors in controls. Results indicate that tryptophan shortens the increased immobility time and reduces social and aggressive behavior in STZ-D mice. Therefore, the reported reductions in the brain-tryptophan concentrations in STZ D mice may participate in regulating their behavior. PMID- 1756901 TI - Aggregation of subclinical autonomic nervous system dysfunction and autoantibodies in families with type I diabetes. AB - The purpose of our study was to evaluate the occurrence of autonomic nervous system autoantibodies (ANS) in the nondiabetic family members of insulin dependent (type I) diabetic subjects. We studied 24 families, including 45 nondiabetic parents and 53 nondiabetic siblings of a type I diabetic proband. One hundred one nondiabetic population control subjects were also studied. Stored sera from nondiabetic family members and control subjects were evaluated for the presence of complement-fixing (CF) adrenal medullary antibodies (CF-ADM), sympathetic ganglia antibodies (CF-SG), and vagus nerve antibodies (CF-V) by indirect immunofluorescence. HLA-DR3 and -DR4 typing was performed on 42 nondiabetic family members and 104 diabetic subjects. One or more CF-ANS were in 45 of 93 (40%) nondiabetic family members compared to 2 of 70 (2.8%) control subjects. CF-SG were in 28 of 92 (30%) family members compared to 0 of 101 control subjects (P = 0.0001). CF-V were in 25 of 95 (26%) family members compared to 0 of 76 control subjects (P = 0.0001). CF-ADM were in 10 of 83 (12%) family members compared to 2 of 70 (2.8%) control subjects (P = 0.056). There was no HLA-DR3 or HLA-DR4 association with ANS. Subclinical autonomic dysfunction was demonstrated in 3 of 4 family members with autoantibodies compared to 0 of 4 family members without autoantibodies. PMID- 1756902 TI - Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. AB - Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT. PMID- 1756903 TI - Intestinal and hepatic cholesterogenesis in hypercholesterolemic dyslipidemia of experimental diabetes in dogs. AB - We previously reported that dog diabetes results in hypercholesterolemia and the accumulation of a high-density lipoprotein (HDL) subclass, HDL1. Hypercholesterolemic diabetic rodents exhibit hyperphagia, intestinal hypertrophy, and increased intestinal cholesterol synthesis and absorption; intestinal 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity is increased, whereas hepatic activity is unchanged or reduced. To determine whether similar mechanisms operate in the hypercholesterolemic diabetic dog, we measured hepatic and intestinal cholesterologenesis. Streptozocin-alloxan-induced diabetic dogs allowed access to food ad libitum were hyperphagic and hypercholesterolemic (10.1 vs. 4.47 mM) but normotriglyceridemic. Plasma HDL1 concentrations were markedly increased. Differences in renal and hepatic function were not statistically significant, except serum alkaline phosphatase, which was elevated 4-fold (P = 0.0003). Urinary mevalonate, an index of whole-body cholesterol synthesis, was increased 6-fold. Intestinal and hepatic weights were both increased, and direct measurements showed crypt and villus thickening. The activity of HMG CoA reductase per gram organ weight was increased 1.7-fold in liver and 2.1-fold in intestine. Calculated whole-organ activity in intestine was nearly twice that in liver. These observations provide strong evidence that intestinal cholesterogenesis is involved in the pathogenesis of hypercholesterolemia in dog diabetes and support the conclusion that increased cholesterol synthesis plays a role in the hypercholesterolemia of diabetes. PMID- 1756904 TI - HLA-DQB1 alleles and absence of Asp 57 as susceptibility factors of IDDM in Finland. AB - It has been proposed that negatively charged aspartic acid at position 57 of the HLA-DQ beta-chain determines resistance to development of insulin-dependent diabetes mellitus (IDDM), whereas genetic susceptibility to IDDM correlates with a neutral amino acid residue. The disease rate is very low in Oriental populations with high frequencies of Asp 57. This raises a question whether the high incidence of IDDM in Finland could be explained by the distribution of this disease marker. In this study, the polymerase chain reaction products of 86 diabetic patients and 115 nondiabetic control subjects were analyzed with seven sequence-specific oligonucleotide probes. Only 25.5% of the diabetic subjects were phenotyped as Asp 57+ compared to 82% of control subjects, which suggests that Asp 57 negativity is a definite risk marker for developing IDDM in Finnish patients. However, the susceptibility conferred by various non-Asp and Asp haplotypes was not equally strong: DQw8 was the most important risk marker and DQw6 the most protective one. The frequency of Asp 57+ DQw4 was similar in diabetic patients and control subjects. The highest genotype-associated relative risk was defined by DQw2/DQw8 heterozygosity (RR 91), whereas it was 13 for non Asp homozygosity. In the control subjects, the frequency of Asp 57+ phenotypes was higher than in several white populations with lower IDDM incidence figures. We conclude that the disease risk in Finland appears to be most strongly related to specific Asp 57- alleles, although other HLA- or non-HLA-associated genes may also contribute to IDDM susceptibility in this population. PMID- 1756905 TI - Decreased incorporation of long-chain fatty acids into erythrocyte phospholipids of STZ-D rats. AB - We studied the mechanisms for the altered fatty acid composition in erythrocytes (RBCs) derived from streptozocin-induced diabetic (STZ-D) rats. After 3-wk duration of diabetes, blood glucose, plasma triglyceride, and plasma free-fatty acid levels were all significantly increased. In the diabetic platelet-poor plasma (PPP), the most significant increases in free fatty acids were stearate, linoleate, eicosatrienoate (n-6), and docosahexaenoate (n-3). Fatty acid composition of RBC phospholipids was also altered, with significant decreases in arachidonate, docosatetraenoate (n-6), and docosapentaenoate (n-6) and increases in linoleate and docosahexaenoate. Insulin treatment of the diabetic rats resulted in normalization of docosapentaenoate, arachidonate, and linoleate levels in RBC phospholipids but not of docosahexaenoate or docosatetraenoate levels. The incorporation of [5,6,8,9,11,12,14,15-3H]arachidonate into diabetic RBC phospholipids was significantly decreased compared with the corresponding control RBC, regardless of the incubation medium used, which was the PPP derived either from the control or diabetic rats. Therefore, the decreased incorporation of [5,6,8,9,11,12,14,15-3H]arachidonate into diabetic RBC phospholipids was independent of the altered lipid composition of the PPP incubation media. Furthermore, the decreased incorporation was not specific for arachidonate, because the incorporation of other long-chain fatty acids such as [9,10 3H]oleate, [1-14C]palmitate, [2-14C]eicosatrienoate (n-6), and [1-14C]linoleate into RBC phospholipids was also comparably decreased. More important, the decreased fatty acid incorporations were reversed by insulin treatment of the diabetic rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756906 TI - Pioglitazone hydrochloride inhibits cholesterol absorption and lowers plasma cholesterol concentrations in cholesterol-fed rats. AB - Diabetes is associated with altered cholesterol metabolism that may contribute to cardiovascular complications. Treatment of rats with pioglitazone hydrochloride, a novel antidiabetic compound that improves the general response of target cells to insulin, significantly lowered cholesterol levels in rats fed a hypercholesterolemic diet and produced a significant reduction in cholesterol absorption. Drug treatment was ineffective in rats that were not given dietary cholesterol. To determine whether these effects of pioglitazone hydrochloride might be related to the known ability of this compound to improve the response to circulating insulin, similar studies were conducted in streptozocin-induced diabetic rats with and without insulin replacement. Diabetic rats absorbed a greater percentage of dietary cholesterol than control rats. Treatment of insulin deficient diabetic rats with pioglitazone alone did not affect cholesterol absorption; however, the combination of insulin and pioglitazone was synergistic to lower absorption of cholesterol and circulating cholesterol and triglycerides. Treatment of either normal rats or diabetic rats receiving insulin with pioglitazone hydrochloride produced a twofold decrease in the ratio of total cholesterol to high-density lipoprotein cholesterol. These results suggest that treatments that improve insulin sensitivity may also have a positive impact on coronary artery disease associated with diabetes. PMID- 1756907 TI - Insulinlike effects of sodium selenate in streptozocin-induced diabetic rats. AB - Treatment of streptozocin (STZ)-induced diabetic rats with sodium selenate (10-15 mumol.kg-1.day-1) for 7 wk resulted in a decrease in plasma glucose, food intake, and water intake to control or near control levels. Plasma insulin was reduced in control rats given sodium selenate to the level found in the diabetic and treated diabetic group. Treatment did not affect control rats with regard to the other measurements cited. Sodium selenate enhanced weight gain in responding diabetic rats to that seen in controls; sodium selenate's actions thus resembled those of insulin. Thus selenate, like vanadium, appears to have insulinlike effects when administered in vivo. PMID- 1756908 TI - Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy. AB - Offspring of women with insulin-dependent diabetes mellitus (IDDM) have a significantly lower risk of IDDM than the offspring of men with IDDM. Furthermore, a negative association of the risk of IDDM in the offspring with maternal age at delivery has been reported. This study tested the association with maternal age in an independent set of families (n = 103) in which the mother had at least one pregnancy before and after the onset of IDDM. In the 304 offspring, the mean +/- SE risk of IDDM by age 20 was 6.0 +/- 2.4% for those born at maternal ages less than 25 yr, whereas, the risk was significantly lower (0.7 +/- 0.7%) for those born at older maternal ages (P = 0.03). These 304 offspring were combined with a sample of 1391 offspring previously reported for a multivariate analysis of other factors related to pregnancy. In the combined analysis, the risk of IDDM in offspring born at maternal ages greater than 25 yr was one-fifth that for offspring born to younger mothers. The risk of IDDM in the offspring was not significantly related to birth order, mother's age at first pregnancy, or the interval between pregnancies for subsequent ones. The risk for the children born before the mother's onset of diabetes was higher than that for those exposed in utero to her diabetes, but the difference did not reach statistical significance. In conclusion, although genetic factors are important determinants of susceptibility to IDDM, exposure to maternal diabetes protects offspring from IDDM during the first 2 decades of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756909 TI - Charge selectivity of proteinuria in type I diabetes explored by Ig subclass clearance. AB - To investigate the role of protein charge in early diabetic proteinuria, the clearance of proteins differing in charge and/or size (anionic and cationic Igs, albumin) was evaluated in 98 insulin-dependent (type I) diabetic patients selected as a representative sample of the 418 patients attending our clinics. Of the patients, 12.9% were microalbuminuric and 4.8% were macroalbuminuric. Anionic and total IgG clearances were significantly increased in 30.6 and 12.2% of patients and were correlated with duration of disease. Anionic IgG4 clearances were increased in patients (9.2%) with normal IgG excretion, suggesting that charge-selectivity impairment is responsible for protein loss. Anionic Ig clearances were also higher in some patients (14.3%) with normal albumin clearance, probably as a result of different glomerular filtration and/or tubular reabsorption. The anionic-cationic IgG clearance ratio tended to increase in parallel with albumin clearance, but once above macroalbuminuric levels, it tended to fall again, indicating the concomitant presence of size-selectivity loss. The anionic IgG clearance and the anionic-cationic IgG ratio, in addition to albumin excretion, may be valuable in assessing early kidney protein charge selectivity impairment and better characterizing normoalbuminuric patients and those in the preclinical stage of diabetic nephropathy. PMID- 1756910 TI - Islet amyloid polypeptide and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated, and dexamethasone-treated rats. AB - Rats from four experimental treatment groups, including fed controls, 24- to 30-h fasted, dexamethasone-treated, and intraperitoneal glucose-treated, were used to assess the effects of these treatments on the immunohistochemically detectable islet amyloid polypeptide (IAPP) content in the pancreatic islets. Isolated perfused pancreases from additional animals in these groups were used to assess insulin and IAPP secretion and relative amounts of these hormones secreted into the perfusate under low-glucose (2.75 mM) and high-glucose (16.7 mM) conditions. Insulin and IAPP concentrations in the perfusate were measured by radioimmunoassays. Titration of immunohistochemical staining revealed the highest levels of IAPP in the dexamethasone- and glucose-treated groups, followed by the fed controls; the least amount was observed in the fasted group. In the perfusion experiments, the dexamethasone-treated group had significantly higher IAPP secretion than did all of the other groups under stimulation with 16.7 mM glucose. In addition, both dexamethasone treatment and glucose treatment increased the relative amount of IAPP to insulin secretion during 16.7 mM glucose stimulation in comparison with fed controls and fasted groups. Fasting tended to have the opposite effect and significantly decreased the relative amount of IAPP to insulin secreted under stimulation with 16.7 mM glucose. In all groups, IAPP and insulin secretion were generally parallel, which is consistent with their colocalization in the beta-cell secretory vesicle and co-release after glucose stimulation. However, significant differences in the insulin-IAPP ratios between experimental groups is consistent with the hypothesis that production of IAPP and insulin are regulated differently in the beta-cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756911 TI - Enhanced stimulation of diacylglycerol and lipid synthesis by insulin in denervated muscle. Altered protein kinase C activity and possible link to insulin resistance. AB - Denervated muscle is generally regarded as insulin resistant because the ability of insulin to stimulate glucose transport and glycogen synthesis is impaired. Previous studies indicate that insulin resistance in these muscles is likely due to a defect at a postreceptor site in the signaling pathway. Because glucose transport into cells has been reported to be linked to changes in diacylglycerol (DAG) and protein kinase C (PKC), we investigated the effect of denervation on the content and synthesis of DAG and the activity and distribution of PKC in the soleus muscle. The DAG content in muscles denervated for 24 h was 40% greater than in control muscles. This was associated with a two- to threefold increase in the percentage of total PKC activity that was membrane associated, with no significant change in total PKC activity, suggesting an increase in PKC activity in vivo. Studies of glucose disposition confirmed that the stimulation of glycogen synthesis by insulin and, to a lesser extent, 2-deoxyglucose uptake were impaired by denervation. However, the stimulation by insulin of glucose incorporation into DAG and other lipids was two- to threefold greater in denervated than in control muscles, and conversion of glucose to lactate and pyruvate and glucose oxidation to CO2 were unchanged. The results reveal a dichotomy in the effects of denervation on various actions of insulin, with both insulin resistance and hyperresponsiveness occurring in different pathways of glucose metabolism. They also reveal a potential mechanism for the elevation of muscle DAG after denervation. The results do not support a direct link between DAG-PKC and glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756912 TI - Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects. AB - We investigated the prevalence of mutations in the gene encoding the major insulin-responsive facilitative glucose transporter (GLUT4) in patients with non insulin-dependent diabetes mellitus (NIDDM). All 11 exons of the GLUT4 gene from 30 British white subjects with NIDDM were amplified using the polymerase chain reaction and screened for nucleotide sequence variation using the single-stranded conformation polymorphism (SSCP) method. No variation between the study subjects was detected in exons 1-3, 4b-8, and 10. Variant SSCP patterns were detected in exons 4a and 9. SSCP variation in exon 4a was revealed by direct nucleotide sequencing to be due to a common silent polymorphism (AAC----AAT at Asn130). One NIDDM patient demonstrated a variant SSCP pattern in exon 9. This was caused by a point mutation (GTC----ATC) at codon 383, which leads to the conservative substitution of isoleucine for valine in the putative fifth extracellular loop of the transporter. Allele-specific oligonucleotide hybridization was used to examine the frequency of this mutation in 240 Welsh white subjects (160 with NIDDM and 80 controls). The Val----Ile383 mutation was found in the heterozygous state in two diabetic subjects and no control subjects. We conclude that mutations of the GLUT4 coding sequence are very uncommon in this population of subjects with typical NIDDM. Determining whether the Ile383 GLUT4 variant present in 3 diabetic subjects contributes in any way to their disease will require further study. PMID- 1756913 TI - Comparative analysis of potency of splenic dendritic and adherent cells (macrophages) as alloantigen presenters in vivo. AB - Dendritic cells and macrophages have been attributed with stimulatory capacity for in vivo and in vitro immune responses. However, the relative contribution of each of these cell types has long been in dispute. Therefore, the differential ability of dendritic cells and macrophages (splenic adherent cells [SACs]) to stimulate pancreatic islet allograft rejection in reversed alloxan-induced diabetic rats was examined. Rats bearing established allografts were challenged with various dosages of donor-strain dendritic cells or SACs, and graft rejection was assessed by analysis of plasma glucose levels and/or histological criteria. Marked differences in the ability to stimulate allograft rejection were observed at the 10(5)-cell dosage; 10(5) dendritic cells induced graft rejection in five of six rats (1 rat required 2 injections), whereas 10(5) SACs failed to induce rejection in four of four rats (P less than 0.10, chi 2 test). Challenge stimuli consisting of less than or equal to 10(5) SACs or less than or equal to 10(4) dendritic cells failed to induce graft rejection. These findings indicate that dendritic cells are potent stimulator cells for in vivo immune responses. Previous studies indicated that as few as 10(3) dendritic cells initiate allograft rejection in nondiabetic recipients. That more dendritic cells were required to stimulate rejection in reversed diabetic recipients compared with nondiabetic recipients suggests that other factors, such as the diabetic state and the production of a tolerant status achieved by larger amounts of grafted tissue, may influence graft survival. PMID- 1756914 TI - Association of elevated IGF-I levels with increased retinopathy in late-onset diabetes. AB - Insulinlike growth factor I (IGF-I) has been suggested to play a role in the pathogenesis of proliferative diabetic retinopathy (PDR). We determined IGF-I levels in subjects in a large population-based study of 928 people with diabetes diagnosed at 30 yr of age or older. PDR was found in 15.7% of the insulin-using group (n = 517) and in 2.8% of those not using insulin (n = 397). The mean serum level of IGF-I was 208 micrograms/L in individuals using insulin and 222 micrograms/L in those not using insulin, both significantly lower than in a nondiabetic comparison group (278 micrograms/L, P less than 0.0001). Logistic regression analysis was used to examine the relationship between IGF-I and PDR while controlling for other factors associated with the presence of PDR. After controlling for duration of diabetes, glycosylated hemoglobin, systolic blood pressure, presence of proteinuria, and age at diagnosis, higher levels of IGF-I were significantly associated with an increased frequency of PDR (P = 0.025) in the group using insulin. In individuals not using insulin, higher levels of IGF-I were associated with an increased frequency of PDR or moderate non-PDR (P = 0.08). These data suggest that higher IGF-I levels may be a risk factor for the development of severe retinopathy in people with diabetes diagnosed at 30 yr of age or older. PMID- 1756915 TI - Impaired expression of glycogen synthase mRNA in skeletal muscle of NIDDM patients. AB - Based on recent studies of the abnormal physiology and biochemistry of the glycogen synthesis in skeletal muscle of non-insulin-dependent diabetes mellitus (NIDDM) patients and their first-degree relatives, the key enzyme of this pathway, glycogen synthase (GS), is considered a candidate gene in the pathogenesis of insulin resistance. Comparing matched groups of 14 NIDDM patients with 14 control subjects, we found that impaired insulin-stimulated nonoxidative glucose metabolism of peripheral tissue (P less than 0.02) and reduced total GS activity (P less than 0.05) of vastus lateralis muscle from patients with NIDDM were accompanied by a 39% reduction (P less than 0.02) in the steady state level of GS mRNA per microgram DNA of muscle. In both diabetic and control subjects, the mRNA expression of GS was unaffected after euglycemic-hyperinsulinemic clamp for 4 h. With single-stranded conformation polymorphism analysis of the entire coding sequence of the GS gene, we were unable to detect any genetic variants in a subset of eight NIDDM patients. We conclude that abnormal pretranslational regulation of the GS gene may contribute to impaired glycogen synthesis of muscle in NIDDM. Our studies give no evidence for structural changes in the coding region of the GS gene, and it is unknown if the decreased mRNA expression is due to impaired transcription or accelerated degradation of the transcript. PMID- 1756916 TI - Improved patient care using the A/S/G/E guidelines on quality assurance: a prospective comparative study. AB - The American Society for Gastrointestinal Endoscopy has promulgated guidelines on quality assurance in gastrointestinal endoscopy. Thorough documentation of endoscopy reports and a peer review process were strongly recommended. We evaluated 1408 dictated endoscopy and colonoscopy reports for deficiency in reference to the guidelines during three periods: 6 months before (group 1), 6 months after the application of the guidelines (group 2), and 5 months of intensive peer review process (group 3). Deficiency was defined as lack of documentation of at least 1 of the 10 parameters that should be included in endoscopy reports according to the guidelines. There was a significant decrease in deficiency rates in groups 2 (91.6%) and 3 (32.7%) compared with group 1 (99.8%) (p less than 0.01). Peer review and direct confrontation of the endoscopists with their deficiencies significantly reduced the use of inappropriate indication for endoscopy (1.5%/group 3 vs. 5.2%/group 1, p less than 0.01). Adherence to the A/S/G/E guidelines on quality assurance improved documentation, decreased inappropriate use of endoscopy, and may thus improve quality of care. PMID- 1756917 TI - Herpes esophagitis: clinical syndrome, endoscopic appearance, and diagnosis in 23 patients. AB - The unexpected diagnosis of herpetic esophagitis in a patient with nausea led us to review our experience with this disease. Review of our records from 1979 to 1989 produced 23 cases proven by endoscopic culture or microscopic examination (Cowdry-type A inclusions), the largest such series reported to date. Twenty-two of the 23 patients were immunocompromised. Odynophagia and chest pain were each present in half of the cases, but 26% of patients had neither. Gastrointestinal bleeding was attributable to herpetic esophagitis in 30%. Thirty percent of patients had disseminated herpes simplex infection and 70% had simultaneous infections with other organisms. Endoscopic findings included nonspecific inflammation, discrete ulcers, coalescent ulcers, and pseudomembranous esophagitis. Herpes virus was not suspected endoscopically as the cause of esophagitis in 30% of cases. Culture was slightly more sensitive than microscopic examination for diagnosis (89% vs. 76%), but both methods should be employed in any immunocompromised patient with esophagitis. PMID- 1756918 TI - Follow-up of hot biopsy forceps treatment of diminutive colonic polyps. AB - Although the hot biopsy technique is widely used to treat diminutive colon polyps, there is concern over its efficacy and safety. Our study involved 39 patients undergoing routine colonoscopy in whom 62 diminutive polyps were found in the rectosigmoid. These lesions were treated with hot biopsy forceps in the standard manner. Flexible sigmoidoscopy was repeated 1 and 2 weeks later with the original treatment sites being identified. Eleven of the 62 sites (17%) revealed persistent viable polyp remnants, indicating incomplete treatment. In terms of safety, there were no clinical complications in this small study and most post biopsy ulcers were healed by 2 weeks. This study shows that the hot biopsy technique may be unreliable in eradicating diminutive colon polyps. PMID- 1756919 TI - Randomized comparison of endoscopic microwave coagulation and endoscopic sclerosis in the treatment of bleeding peptic ulcers. AB - We conducted a prospective randomized trial to evaluate the effectiveness and safety of endoscopic microwave coagulation in comparison to endoscopic sclerosis in the treatment of peptic ulcer bleeding. Over 15 months 127 ulcer-bleeding patients with an actively bleeding vessel (N = 21), a non-bleeding vessel (N = 53), oozing hemorrhage (N = 25), or an adherent clot (N = 28) in the ulcer base were randomly assigned during endoscopy to receive treatment with endoscopic sclerosis or with microwave coagulation. There were no significant differences in effectiveness between endoscopic sclerosis and microwave coagulation in any of the assessed parameters: the percentage of patients with major recurrent hemorrhage (5 vs. 12), the percentage who needed emergency surgery (5 vs. 9), the mean (+/- SD) transfusion requirements (0.32 +/- 0.89 vs. 0.78 +/- 1.65), the mean number of hospital days (10.3 +/- 3.5 vs. 10.7 +/- 4.1), and the number of deaths due to bleeding (0 vs. 2) were similar in both groups. No case of perforation occurred in either group. The data suggest that microwave coagulation is as effective and safe as endoscopic sclerosis in the treatment of bleeding peptic ulcers. PMID- 1756920 TI - Evaluation of a voice recognition system for generation of therapeutic ERCP reports. AB - We evaluated a computerized report-generating system using voice recognition technology (EndoSpeak) for producing therapeutic ERCP reports. For 30 consecutive ERCP cases, reports using both EndoSpeak and standard dictation were generated at the end of the procedure. The cases were scored for overall difficulty and the number of component procedures performed. The time to generate a report with EndoSpeak was significantly longer than with dictation (10.0 +/- 2.9 (SD) min vs. 6.5 +/- 1.6 min, p less than 0.0001), and this difference was greater for more lengthy reports (r = 0.85, p less than 0.001). The procedure difficulty score and the number of component procedures were both significant predictors of the physician's report generation time for EndoSpeak and dictation. Dictated reports were judged to have a higher information content than EndoSpeak reports for 90% of the cases (p less than 0.00001). Several specific difficulties were encountered with the EndoSpeak software. Although EndoSpeak offers promise, substantial software modifications will be required before this system can become competitive with dictation for therapeutic ERCP reports. PMID- 1756921 TI - A pure charcoal suspension for colonoscopic tattoo. PMID- 1756922 TI - Sclerotherapy using a small size negative pressure-controlled tube. PMID- 1756923 TI - Anastomosis at flexible endoscopy: an experimental study of compression button gastrojejunostomy. PMID- 1756924 TI - Removal of a broken pancreatic stent using a new stent retrieval device. PMID- 1756925 TI - Splenic injury complicating therapeutic upper gastrointestinal endoscopy and ERCP. PMID- 1756926 TI - Endoscopic management of a bleeding duodenal diverticulum. PMID- 1756927 TI - Proximal common bile duct obstruction secondary to a periampullary duodenal diverticulum: successful treatment with endoscopic stenting. PMID- 1756928 TI - Recurrent acute pancreatitis in pancreas divisum secondary to minor papilla obstruction from a gastrostomy feeding tube. PMID- 1756929 TI - Quality assurance and patient care. PMID- 1756930 TI - American gastroscopy--yesterday and today. PMID- 1756931 TI - Needle knife sphincterotomy. PMID- 1756932 TI - Earlier report of Mallory-Weiss tear with colonic lavage. PMID- 1756933 TI - Treatment of achalasia. PMID- 1756934 TI - A method to overcome dilator placement failure in achalasia patients with markedly dilated esophagus. PMID- 1756935 TI - Warm your contrast. PMID- 1756936 TI - Condyloma, condylomata, and Latin grammar. PMID- 1756937 TI - Patient positioning during colonoscopy. PMID- 1756938 TI - Guidelines for establishment of gastrointestinal endoscopy areas. PMID- 1756939 TI - Tissue sampling and analysis. PMID- 1756940 TI - Proctoring and hospital endoscopy privileges. PMID- 1756941 TI - Technology assessment and the A/S/G/E position statement. PMID- 1756942 TI - A/S/G/E status evaluations on new or emerging endoscopic technologies. PMID- 1756943 TI - Technology assessment status evaluation: endoscopic band ligation of varices. AB - On the basis of limited available data, band ligation appears to be effective for control of active esophageal variceal bleeding and for prevention of recurrent bleeding. It has minimal morbidity and no reported mortality. Preliminary results of a randomized-trial comparing this technique to sclerotherapy show comparable efficacy but band ligation may carry a lower complication rate. Long-term results of ligation are pending. PMID- 1756944 TI - Status evaluation: enteroscopy. AB - Enteroscopy is a method to examine the small bowel mucosa beyond the reach of standard upper endoscopes. In practice it has primarily been used to search for a bleeding lesion in patients where one is not detected by conventional means. Such patients constitute only a small percentage of those who bleed (15,20). Experience is greatest with push enteroscopy. Examination of the distal duodenum and proximal jejunum using a standard or pediatric colonoscope is practical, appears to be safe and provides a satisfactory diagnostic and therapeutic yield in experienced hands. Longer designated push enteroscopes are under investigation. Sonde type enteroscopes can be passed to the ileum in most cases. A cause for bleeding can be detected in approximately one-quarter to one-third of individuals with minimal morbidity. Certain technical problems limit their efficacy and their role in the evaluation of patients with bleeding has not yet been clearly defined. PMID- 1756945 TI - Power of the admixture test to detect genetic heterogeneity. AB - Several dominant genetic diseases which appear to be homogeneous are the expression of genetic mutations at several loci. The power to detect linkage by likelihood methods is diminished for heterogeneous, as compared to genetically homogeneous, disorders. Using a simulation approach and two pedigrees typical of those available for the study of a dominant disease (with expected lod scores of 0.43 and 1.00 at theta = 0.05 and PIC = .59), I have evaluated the power to detect genetic heterogeneity by using the admixture test. Linkage power was determined by varying the number of families available for study, the recombination fraction (theta), the informativity of the hypothetical marker, and the proportion of linked families, alpha. For moderate and small values of alpha it is feasible to detect genetic heterogeneity once linkage has been established; rarely will it be possible to detect linkage and heterogeneity simultaneously given a limited number of small or moderate pedigrees. PMID- 1756946 TI - Informativeness of twin-nuclear family and nuclear family designs for segregation analysis. AB - This brief note examines the precision of segregation parameter estimates from both twin-nuclear family and conventional nuclear family designs. The program MENDEL was used to derive expected frequencies of different family patterns of affectation (with fixed sibship size) under various single gene models, and then to estimate the standard errors (and information) associated with gene frequency and penetrance values at given sample sizes. As might be expected, a 2- to 5-fold increase in relative efficiency was found for the same family size if families included an MZ twin pair among their offspring. The methods used allow convenient calculation of expected informativeness of a given study design. PMID- 1756947 TI - Inheritance of human plasma dopamine-beta-hydroxylase thermal stability. AB - Although the structural gene for human dopamine-beta-hydroxylase (DBH) has been cloned, the mechanism by which DBH physical properties and activity are regulated is not well understood. Previous reports have suggested that three-allele or two locus models may account for the genetic regulation of these traits in human blood. It is an interesting challenge to determine the extent to which quantitative analyses will complement or guide molecular genetic studies. In this study we analyzed data on the physical property of DBH thermal stability and DBH activity in 230 individuals in 53 families in an attempt to clarify genetic mechanisms for the inheritance of these traits. Commingling and segregation analyses of the thermal stability data provided the first clear evidence of a major gene polymorphism for DBH thermal stability analyzed as a quantitative trait. Major gene transmission was supported within a mixed model (chi 2[3] = 13.39, P less than .004). In keeping with earlier findings, similar analyses of DBH activity provided strong evidence of genetic transmission. However, in our data support for a major gene polymorphism was equivocal (chi 2(2) = 2.99, P = .22). PMID- 1756948 TI - Genetic epidemiology of childhood brain tumors. AB - The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome. PMID- 1756949 TI - Linkage analysis of low-density lipoprotein subclass phenotypes and the apolipoprotein B gene. AB - A common heritable phenotype has recently been identified which is characterized by a relative abundance of small, dense low-density lipoproteins (LDL), and mild elevations of plasma triglycerides and reductions in plasma high-density lipoproteins (HDL) cholesterol. This phenotype, designated LDL subclass phenotype B, has been associated with up to a three-fold increase in coronary disease risk. Complex segregation analysis in two large family studies has demonstrated that LDL subclass phenotype B is influenced by an allele at a single genetic locus with a population frequency of 0.25-0.3, and autosomal dominant inheritance, but with full penetrance only in males age 20 and over and in postmenopausal women. Since apolipoprotein B (apoB) is the principal protein component of LDL, linkage analysis was used to investigate possible linkage between the phenotype B phenotype and the apoB gene, using a variable number of tandem repeats site located 0.5 kb from the 3' end of the apoB gene. In 6 informative families including only family members in the penetrant classes, a total LOD score of 7.49 was found at a recombination fraction of 0.001. Thus, under the assumptions of the single gene model, it is unlikely that the apoB locus controls LDL subclass phenotype B. PMID- 1756950 TI - Commentary: the affected sib-pair method in the context of an epidemiologic study design. AB - The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases. PMID- 1756951 TI - Biological factors and psychometric intelligence: a review. AB - Results from a synthesis of correlations between psychometric intelligence and two physical traits, head size and body size, are reported. Within-family studies are reviewed for evidence of pleiotropy, the effect of a single genetic factor on two traits. Studies are also reviewed to determine whether prenatal effects bias twin studies, leading to underestimates of genetic influence. An N-weighted mean partial correlation (controlling height) of .10 between intelligence and head size was found. Using a method developed by Van Valen (1974), the correlation of intelligence and brain size was estimated as .29 based on all the intelligence/head-size studies of adults and adolescents, and .44 based on studies measuring intelligence with IQ tests. The N-weighted mean partial correlations (controlling age) of intelligence and height were .18 for children and .22 for adults. The within-family studies indicated that pleiotropy may contribute to the correlation of intelligence with head size and to the correlation of intelligence with body size. Prenatal effects are not an important source of bias in twin studies or for heritability estimates based on them. PMID- 1756952 TI - [Effect of ploidy and the status of the MAT locus in Saccharomyces cerevisiae yeast cells on the mitotic stability of episomal plasmids and the level of expression of the HBsAg gene of hepatitis B virus]. AB - The frequency of the YEp13, pEF91, YEp13 + HBs, pNMVG3954 plasmids' elimination in a series of isogenic strains n. 2n and 3n was studied. Plasmid stability and the level of expression of the gene of hepatitis B surface antigen (HBsAg) increased in polyploid transformants as a result of increase in plasmid copy number. Heterozygotes MATa/MAT differed from the homozygotes in higher stability of YEp13, pEF91, and YEp13 + HBs plasmids having the same quantity of the HBsAg antigen. The appearance of negative properties--destabilization of episomal plasmids or decrease in synthesis of heterologous protein have been discovered in certain diploid cell. These results point to limitations in constructing a polyploid producer on the basis of the similar type of genome. PMID- 1756953 TI - [Expression of the pro-opiomelanocortin gene in rats with inherited arterial hypertension]. AB - Expression of pro-opiomelanocortin (POMC) gene in pituitary of rats from newly developed hypertensive strain (ISIAH strain) was studied by dot hybridization. The pUC8 plasmid containing 900 base pair (bp) segment or the human POMC gene corresponding to the major portion of the 3'-nontranslated mRNA region and 60 bp coding for the signal peptide, was used as a probe for hybridization. It was found that the expression of the POMC in pituitary of the hypertensive JSJAH rats was more than 3-fold gene lower as compared to normotensive Wistar strain. The latter is the original strain from which the ISIAH rats were bred. The mechanism of this phenomenon and its possible relation to the arterial hypertension are discussed. PMID- 1756954 TI - [The interrelation of the polytene chromosomes of generative tissues in Drosophila melanogaster]. AB - The principles of three dimensional organization of primary and secondary orders polytene chromosomes in ovarian nurse cells of Drosophila melanogaster were elucidated. Contrary to somatic tissues, no joining of chromosome arms into local chromocentre was discovered. The chromosomes are separated in the nuclear space and are attached to the nuclear envelope by the centromeric (and the XL arm--by the telomeric) sites, the arms of autosomes (especially primary polytene chromosomes) being separated in the area of attachment. Polytenized XR arm of the X chromosomes were discovered. The architecture of chromosomes discovered in ovarian nurse cells is tissue-specific and differs considerably from the organization of polytene chromosomes of somatic tissues. PMID- 1756955 TI - [Interspecies differences of co-orientation of primary polytene chromosomes in ovarian nurse cells in Drosophila melanogaster, D. simulans and D. mauritiana]. AB - Essential differences in the architecture of primary polytene chromosomes in ovarian nurse cells between Drosophila melanogaster, D. simulans and D. mauritiana were discovered. The individual chromosomes of D. melanogaster (as well as their arms) are separated significantly from each other and are attached to the nuclear envelope by the centromeric (and the XL arm--by the telomeric) sites. D. simulans has the combination of the centromeric parts of the chromosomes X, 2, 3 into the "elongated" chromocentre, and in addition, the arms of chromosomes are also separated and attached to the nuclear envelope. Unlike the rest of the chromosomes, D. mauritiana has the chromosome 3 with firm combinated arms and the large heterochromatic block in the centromere, without being attached to the nuclear envelope. PMID- 1756956 TI - [Genetic recombination and steroid metabolism in Drosophila]. AB - A double-species ecologo-genetical model, including Drosophila and yeast, has been used as a new methodological instrument for investigation of the physiological mechanism of recombination. Incubation of Drosophila females in the medium containing yeast of the strain mutant for ergosterol synthesis leads to suppression of temperature-induced crossing over. The mass-spectrum analysis of steroid fraction from Drosophila females has shown that incubation of the yeast medium without ergosterol results in arrest of ecdysterone synthesis. These data are explained by the absence of ecdysterone synthesis precursor in the fly organism. The endocrinal control of crossing over is discussed in the light of hormonal regulation of meiosis. PMID- 1756957 TI - [Genotypic differences in the level of N-acetyltransferase activity in mice of inbred lines and their hybrids]. AB - There are "slow" and "rapid" acetylator phenotypes in mice according to N acetyltransferase activity (E.C. 2.3.1.5) (N-AT). The results of direct, back- and reciprocal crosses of mice lines with rapid acetylation phenotype (C57BL/He) show monogenic autosomic control of acetylation locus (Ac) with rapid allele dominance and sex dependence upon N-AT activity in males. So, genetic polymorphism according to the Ac locus exists in mice as well as in some other animal species and in humans. The results obtained in this study demonstrated the correlation between the N-AT level in mice and their predisposition to malignant tumors as well as dependence of cyclophosphamide action on the N-AT activity upon the genotype of an individual, which suggests a certain role of the Ac locus in tumor development. PMID- 1756958 TI - [Adaptive norm and stabilizing selection for anthropometric characters at birth]. AB - Analysis carried out on medical documentation containing data on several thousand healthy and affected babies has revealed patterns of differential mortality and differential morbidity for newborns and infants which allow to estimate relative risk as a function of birth weight and body length. Adaptive norm for anthropometric traits at birth was defined as the weight or length interval in which mortality/morbidity rates were lower than the overall population level. The intensity of stabilizing selection associated with birth weight calculated from these data is several times higher in the neonatal period than for the age interval 1-12 months. Neonatal mortality in more than 50% cases can be attributed to the effects of stabilizing selection associated with birth weight. PMID- 1756959 TI - [Empirical, free of genetic model, estimation of recurrence risks in multifactorial diseases: conditional probability approach]. AB - Conditional probability approach in estimation of recurrence risks in sibships of different parental phenotypic matings with the different set of affected and normal siblings is considered. The formulae are presented for calculation of recurrence risks in cases of equal and different susceptibility of two sexes under different ways of sampling of family data: direct selection of offsprings through the parents; indirect selection of offsprings through affected siblings- the probands, under different ascertainment probability--from pi = 1.0 ("exhaustive selection") up to pi----0 ("single selection"); for the case of different susceptibility of the two sexes a possibility of the differences in the ascertainment probabilities of men (pi m) and of women (pi w) is allowed, unlike "independent ascertainment model", which requires the constancy of pi. The case of multiple incompatible subforms is considered for estimation of the recurrence risks of the specified subforms. The methods of the risks estimation proposed are free of genetic models being universal both for classical mendelian traits (with the constant risks) and for multifactorial ones (with variable risks). PMID- 1756960 TI - [Excision repair does not protect Bacillus subtilis cells from inactivation by sunlight]. AB - Exponentially growing Bacillus subtilis cells are highly sensitive to inactivating action of sunlight, the strain deficient in excision repair being every more sensitive than the uvr1 mutant. The inactivating effect is connected with the action of irradiation located in the left part of the spectrum (the whole UV region and some zones of the visible one). Increased sensitivity to sunlight disappeared when cells were exposed to sunlight in a liquid medium with casaminoacids (2 g/l). The inactivating effect was probably of photodynamic nature and was caused either by DNA lesions that were not removed by excision repair or by the damage which arose not in DNA. PMID- 1756961 TI - [A new case of a syndrome including marfanoid phenotype and craniostenosis]. AB - A new case of the syndrome with craniosynostosis and Marfanoid features is reported. The data presented and the analysis of relevant literature are suggestive of a community of the Marfanoid features with clinical and genetic heterogeneity. The possibility to delineate the Marfanoid syndrome with craniosynostosis as a nosologic unit and its etiology are discussed. PMID- 1756962 TI - Genetic analysis of extra sex combs in the hybrids between Drosophila subobscura and D. madeirensis. AB - Drosophila subobscura and D. madeirensis are closely related species, the first distributed over a large area and the latter restricted to the island of Madeira. These species can hybridize in laboratory conditions, yielding fertile females and sterile males. Hybrid offspring show several phenotypic anomalies, including sex combs on the second and third pairs of legs in males. The extra sex comb trait is a homeotic transformation of the mesothoracic and metathoracic legs into prothoracic legs. This anomaly is observed almost exclusively in F1 males with D.madeirensis mothers. Analysis of backcross males shows that D.subobscura and D.madeirensis have diverged at a minimum of four autosomal loci affecting the extra sex comb anomaly. In addition, some incompatibility involving the X chromosome and/or a maternal effect is also implicated. PMID- 1756963 TI - Developmental stability in hybrids between the sibling species pair, Drosophila melanogaster and Drosophila simulans. AB - Drosophila melanogaster and its sibling species D.simulans were hybridized in the laboratory to test the hypothesis that developmental homeostasis in hybrids between two species having no prior gene flow would be significantly reduced. Developmental stability was assessed by measuring fluctuating asymmetry for three bilateral traits: sternopleural chaetae, wing length, and fronto-orbital plus frontal chaetae. Male F1 hybrids showed no decrease in developmental stability compared to males of parental species. Female hybrids showed significant fluctuating asymmetry compared to other flies. The results are discussed with respect to ideas about coadaptation and gene flow based upon previous studies of hybrid developmental stability. PMID- 1756964 TI - Differential flight activity among karyotypes: daily and weather-induced changes in chromosomal inversion polymorphism in natural populations of Drosophila subobscura. AB - The question is posed whether karyotype frequencies in the active fraction of Drosophila subobscura populations vary consistently in the course of a day, or in accordance with weather changes. Significant daily variation occurred in all chromosomes with the exception of the sex chromosome. The proportions of the karyotypes Ust/1+2 and Ist/st decreased from early to late morning and increased during the evening. Ist/1 displayed a complementary behaviour. The homokaryotypes Ost/st and Est/st decreased both during the morning and the evening. Weather disturbances caused a remarkable variation in the frequencies of the standard gene arrangements. PMID- 1756965 TI - Spectrum of mutations that occur under selective and non-selective conditions in E. coli. PMID- 1756966 TI - Molecular phylogeny of the subgenus Sophophora of Drosophila derived from large subunit of ribosomal RNA sequences. AB - RNA sequencing has been used to assess the relationships among species of the subgenus Sophophora of the genus Drosophila. Two divergent domains, D1 and D2, of the large ribosomal RNA (28S), totalling 550 nucleotides have been sequenced using the rRNA direct sequencing method. A tree has been reconstructed from the neighbor-joining algorithm and the confidence intervals were evaluated by the bootstrap procedure. Results have shown that the branching of the willistoni and saltans groups of the subgenus Sophophora is very ancient and probably predates that of the subgenus Drosophila. The other groups and subgroups of Sophophora are clustered in three main lineages: 1) the melanogaster and oriental subgroups; 2) the montium subgroup; 3) the ananassae subgroup of the melanogaster group clustered with the fima and obscura groups. Thus, in comparison with our results, several taxa of various ranks appear paraphyletic (the genus Drosophila, the subgenus Sophophora and the melanogaster group). Our biochemical phylogeny is only in partial agreement with the pattern of Throckmorton's radiations as well as with classical taxonomy, both based on morphological data. PMID- 1756967 TI - Tissue specific expression of the Drosophila Adh gene: a comparison of in situ hybridization and immunocytochemistry. AB - The tissue specific patterns for Drosophila melanogaster alcohol dehydrogenase (Adh) mRNA and protein expression were determined using in situ hybridization and immunocytochemical techniques. Alcohol dehydrogenase mRNAs were localized in thin sections of frozen tissue using the hybridization of single stranded RNA probes. Alcohol dehydrogenase protein was identified in frozen tissue samples using ADH antisera, a biotinylated secondary antibody, and streptavidin conjugated to horseradish peroxidase. In tissues such as fat body, gastric caeca, and adult cardiac valve, the patterns of expression for ADH protein and mRNA were identical. Other tissues such as oocytes, nurse cells, imaginal disks, and brain show levels of Adh mRNA that are lower than or equivalent to those observed in the previously mentioned tissues, but they exhibit little or no ADH protein. The lack of concordance between Adh mRNA and ADH protein expression in oocytes and nurse cells may reflect the packaging of maternal mRNAs (but not ADH protein) for use in early development. The reason(s) for the other discrepancies in protein and mRNA expression are not known at this time but may be due to post transcriptional regulation in these specific tissues. PMID- 1756968 TI - Cloning, overexpression and nucleotide sequence of a thermostable DNA ligase encoding gene. AB - Thermostable DNA ligase has been harnessed for the detection of single-base genetic diseases using the ligase chain reaction [Barany, Proc. Natl. Acad. Sci. USA 88 (1991) 189-193]. The Thermus thermophilus (Tth) DNA ligase-encoding gene (ligT) was cloned in Escherichia coli by genetic complementation of a ligts 7 defect in an E. coli host. Nucleotide sequence analysis of the gene revealed a single chain of 676 amino acid residues with 47% identity to the E. coli ligase. Under phoA promoter control, Tth ligase was overproduced to greater than 10% of E. coli cellular proteins. Adenylated and deadenylated forms of the purified enzyme were distinguished by apparent molecular weights of 81 kDa and 78 kDa, respectively, after separation via sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. PMID- 1756969 TI - Cloning, expression and characterization of a cDNA encoding a lipase from Rhizopus delemar. AB - A lambda gt11 cDNA library was constructed in Escherichia coli using poly(A) selected mRNA from the fungus, Rhizopus (Rp.) delemar. Lipase-producing members of the library were identified by means of a phenotypic score wherein the release of fatty acids by lipase causes a characteristic color change in the growth medium. One such isolate contained a 1287-bp insert (LIP cDNA) which hybridizes to 1.25- to 1.35-kb mRNA species from Rp. delemar. The lipase produced in E. coli containing the LIP cDNA exhibits the same substrate selectivity as the authentic fungal enzyme, hydrolyzing ester bonds at the stereospecific numbering (sn) sn-1 and sn-3, but not the sn-2, positions of triglycerides. The complete nucleotide sequence of the LIP cDNA was determined. By reference to the N-terminal sequence of authentic Rp. delemar lipase, the lipase-encoding region was identified within this fragment. The LIP cDNA encodes a putative preprolipase consisting of a 26 amino-acid(aa) signal sequence, a 97-aa propeptide, and a 269-aa mature enzyme. The predicted mature lipase has the same molecular weight and aa composition as that of Rp. delemar, is highly homologous to that produced by the fungus Rhizomucor miehei, and contains the consensus pentapeptide (Gly-Xaa-Ser-Yaa-Gly) which is conserved among lipolytic enzymes. It is concluded that the LIP cDNA is an essentially full-length analogue of the lipase-encoding gene of Rp. delemar. The lipase encoded by the LIP cDNA occupies a cytoplasmic location when synthesized in E. coli. Unprocessed forms of the lipase accumulate in E. coli. PMID- 1756970 TI - Optimised cDNA size selection and cloning procedure for the construction of representative plasmid cDNA libraries. AB - Plasmid libraries are more versatile than phage libraries since they allow expression cloning in eukaryotic systems. However, high numbers of primary clones are sometimes difficult to obtain and more efficient transformation procedures are often required. In this paper, a detailed protocol is presented, for the construction of large plasmid libraries from ng quantities of cDNA, based on a highly efficient transformation step. Drop dialysis and electroporation are optimised: complete ligase removal and yeast tRNA addition before dialysis appear critical, while exclusive use of double-distilled water as well as rapid preparation of fresh cells provide excellent electroporation yields. A novel, simple and flexible cDNA size selection procedure is also presented, based on sucrose density gradient. Two libraries were constructed using an expression vector for mammalian cells (pCDM8) and its Escherichia coli host strain (MC1061[p3]). Numbers of 2 to 10 x 10(6) primary transformants were obtained from 1 microgram of poly(A)+ RNA. Up to 85% of the clones had inserts and half of the inserts were larger than 1.5 kb. PMID- 1756971 TI - SrfI, a new type-II restriction endonuclease that recognizes the octanucleotide sequence, [sequence: see text]. AB - A new restriction endonuclease, SrfI has been isolated from an unidentified species of Streptomyces. SrfI recognizes the 8-bp palindrome, 5'-GCCCGGGC and cleaves double-stranded DNA after the third C in the sequence, producing blunt ends. SrfI is a rare-cutting enzyme and should therefore be useful for megabase mapping. PMID- 1756972 TI - The oligopeptide (Gly-Pro)2-Ala-(Gly-Pro)2 increases the internal proline level and improves NaCl tolerance when produced in Escherichia coli. AB - We have produced various proline-containing peptides as translational fusions with beta-glucuronidase (beta Glu) in Escherichia coli. When these linkers were introduced in the 5'-end of the beta Glu-encoding gene, the production of the enzyme was increased substantially in vivo. The peptides carrying repetitive Gly Pro sequences could also stimulate the growth of the transformants in media with inhibitory concentrations of NaCl. Furthermore, the freezing tolerance could be improved. PMID- 1756973 TI - Characterization of melA: a gene encoding melanin biosynthesis from the marine bacterium Shewanella colwelliana. AB - A recombinant plasmid with the ability to impart melanin synthesis to an Escherichia coli host was isolated from a Shewanella colwelliana genomic library. The genetic determinant of the Mel+ phenotype is carried on a 1.3-kb DNA fragment and sequence analysis of this revealed a single intact open reading frame that was sufficient for melanin synthesis (mel). This gene is expressed as a monocistronic transcript and a putative transcription start point is located 115 nucleotides upstream from the translational start codon. The mel gene encoded a protein of 39.5 kDa [346 amino acids (aa)] that showed no aa sequence homology with other proteins known to mediate melanin synthesis (e.g., tyrosinases). PMID- 1756974 TI - A wide-host-range suicide vector for improving reverse genetics in gram-negative bacteria: inactivation of the blaA gene of Yersinia enterocolitica. AB - A new suicide vector (pKNG101) that facilitates the positive selection of double recombination events in Gram-bacteria has been developed. It contains a conditional origin of replication (oriR6K), the strAB genes encoding the streptomycin phosphotransferase (SmR), an origin of transfer (mobRK2), the sacB gene mediating sucrose sensitivity, and multiple cloning sites. It was used to mutate the blaA gene of Yersinia enterocolitica, by marker-exchange mutagenesis. To do this, we have first cloned into the suicide vector pKNG101, a 2.5-kb fragment of Y. enterocolitica chromosomal DNA encoding the 20-kDa beta-lactamase A. Gene blaA was then mutated in vitro by insertion of luxAB, which resulted in pKNG105. The disrupted blaA gene was then reintroduced into Y. enterocolitica chromosome by homologous recombinations in two steps. First, E. coli SM10 lambda pir (pKNG105) was mated with strains of Y. enterocolitica. This led to the integration of pKNG105 into the chromosome, by a single homologous recombination event. The transconjugants, selected for SmR, were sensitive to sucrose due to the synthesis of levans (toxic compounds), catalysed by levansucrase, the product of sacB. For the second step, a single colony from the first step was grown in rich medium deprived of antibiotic, allowing the occurrence of a second crossing over that replaced the wild-type allele blaA with the mutant one, and then excised the plasmid-borne sacB from the chromosome. Such blaA mutants were selected on their ability to grow on TSA medium containing 5% sucrose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756975 TI - The Saccharomyces cerevisiae ADE1 gene: structure, overexpression and possible regulation by general amino acid control. AB - The ADE1 gene of the yeast Saccharomyces cerevisiae has been cloned by complementation of the ade1 mutation. The nucleotide sequence has been determined for the 918-bp coding region, 240-bp 5'-noncoding region and 292-bp 3'-noncoding region. The sequenced region includes a single large open reading frame coding for a protein of 306 amino acid (aa) residues. The promoter of the ADE1 gene contains a copy of the 5'-TGACTC hexanucleotide, a feature characteristic of promoters under general aa control. Subsequent search of other published purine biosynthesis gene sequences revealed that all of them also contain general aa control signals in their promoter regions. An expression plasmid containing the ADE1 coding region under control of the PHO5 promoter produced N-succinyl-5 aminoimidazole-4-carboxamide ribotide (SAICAR) synthetase in yeast cells at a level of 40% of total cellular protein. One-step purification resulted in an almost homogeneous preparation of SAICAR synthetase. PMID- 1756976 TI - Cloning and analysis of five mitochondrial tRNA-encoding genes from the fungus Beauveria bassiana. AB - Five mitochondrial (mt) tRNA genes from the filamentous fungus, Beauveria bassiana, were cloned and sequenced. The genes encoding the Val-, Ile-, Ser-, Trp and Pro-accepting tRNAs were found clustered in the region 5' to the lrRNA encoding gene. The genes were 64-77% homologous with the equivalent genes from other filamentous fungi, 49-58% to yeasts with the exception of the Val-accepting tRNA-encoding gene which was 76%, and only slightly homologous with Escherichia coli. The B. bassiana mt genetic code was found to be similar to that of other fungal mitochondria in that the UGA codon is used as a signal for Trp rather than as a stop codon. Transcript analysis has revealed that the genes present in tRNA cluster are transcribed and processed into tRNA-size products. Secondary structure models proposed for the gene products show that conservation of tRNA secondary structure also exists. The presence of a GGC sequence rather than a GGU sequence in the D-loop of the tRNA(Trp)-encoding gene is a feature unique to the B. bassiana mt tRNA. An unconventional G-A base pair present in the D-stem of the tRNA(Ser)-encoding gene is a feature conserved in the mt tRNA of other filamentous fungi. Comparison of the B. bassiana tRNA-encoding genes with those of two other filamentous fungi and two yeasts revealed that the differences between closely related species favoured transition-type mutations. PMID- 1756977 TI - Heterologous expression of the Aspergillus nidulans regulatory gene nirA in Fusarium oxysporum. AB - We have isolated strains of Fusarium oxysporum carrying mutations conferring a phenotype characteristic of a loss of function in the regulatory gene of nitrate assimilation (nirA in Aspergillus nidulans, nit-4 in Neurospora crassa). One of these nir- mutants was successfully transformed with a plasmid containing the nirA gene of A. nidulans. The nitrate reductase of the transformants is still inducible, although the maximum activity is lower than in the wild type. Single and multiple integration events were found, as well as a strict correlation between the presence of the nirA gene and the Nir+ phenotype of the F. oxysporum transformants. We also investigated how the A. nidulans structural gene (niaD) is regulated in F. oxysporum. Enzyme assays and Northern experiments show that the niaD gene is subject to nitrate induction and that it responds to nitrogen metabolite repression in a F. oxysporum genetic background. This indicates that both the mechanisms of specific induction, mediated by a gene product isofunctional to nirA, and nitrogen metabolite repression, presumably mediated by a gene product isofunctional to the homologous gene of A. nidulans, are operative in F. oxysporum. PMID- 1756978 TI - The TRP1 gene of Phytophthora parasitica encoding indole-3-glycerolphosphate synthase-N-(5'-phosphoribosyl)anthranilate isomerase: structure and evolutionary distance from homologous fungal genes. AB - The TRP1 gene was isolated from the genome of Phytophthora parasitica. It encodes bifunctional enzyme of the tryptophan biosynthetic pathway indole-3 glycerolphosphate synthase-N-(5'-phosphoribosyl)anthranilate isomerase (IGPS PRAI). The gene was localized and sequenced using random in vitro insertions of omega interposon. The domain structure of the protein product was found to be similar to that of enteric bacteria but different from the structure of homologous enzymes in fungi. Two introns in the IGPS domain were found. This is unique in eukaryotic IGPS-encoding genes so far sequenced. Comparative analysis of the primary structure of IGPS and PRAI domains [neighbor-joining method of Saitou and Nei, Mol. Biol. Evol. 44 (1987) 406-425] confirmed a large phylogenetic distance of TRP1 from corresponding fungal genes. In the resulting distance tree Phytophthora sequences are located outside of the cluster which encompasses all known homologous proteins from fungi indicating that the lineage of oomycetes took a separate course of development before speciation within the fungal line of descent began. Two of the oligopeptide insertions engineered into the F domain of the protein product did not abolish the enzymatic activity of the protein. PMID- 1756979 TI - The isolation, cloning and identification of a vegetative catalase gene from Bacillus subtilis. AB - A Bacillus subtilis library of Tn917::lacZ insertions was screened for mutants that were unable to grow in the presence of normally sublethal concentrations of hydrogen peroxide. The identification and subsequent analysis of one mutant strain, YB2003, which carried the mutation designated kat-19, revealed that this strain was deficient in the expression of a vegetative catalase. Regions of the chromosome both 5' and 3' to the site of the Tn917 insertion, as well as the gene without the insertion (kat-19+) were cloned. The presence of the functional kat 19+ gene on a high-copy plasmid restored catalase activity to the kat-19::Tn917 strain as well as to strains of B. subtilis that carried the katA 1 mutation. While the katA+ locus is believed to represent the structural gene for the vegetative catalase of B. subtilis [Loewen and Switala, J. Bacteriol. 169 (1987) 5848-5851], the sequence analysis of the cloned kat-19+ DNA fragments revealed an open reading frame that showed significant homology between the deduced amino acid sequence of this gene product and that of known eukaryotic catalases. PMID- 1756980 TI - Sequence and expression of the gene encoding 3-phosphoglycerate kinase from Bacillus stearothermophilus. AB - The structural gene (pgk) encoding 3-phosphoglycerate (PGK) from Bacillus stearothermophilus NCA1503, has been cloned in Escherichia coli and its complete nucleotide sequence determined. The gene consists of an open reading frame corresponding to a protein of 394 amino acids (aa) (calculated Mr 42,703) and, in common with other prokaryotic pgk genes, is preceded by the structural gene encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Constructs containing the B. stearothermophilus pgk gene and its flanking sequences in the high-copy plasmid, pUC9, co-express both PGK and GAPDH at high levels in transformed E. coli cells, typically producing PGK at levels of up to 30% of the soluble cell protein. The deduced aa sequence of B. stearothermophilus PGK is compared with those of the mesophilic (yeast) and extreme thermophilic (Thermus thermophilus) enzymes since the crystal structure of these PGKs are known or are in the process of being determined. Changes in the sequences of the three enzymes, as they appear to relate to the enhancement of thermal stability, are discussed. PMID- 1756981 TI - Expression of heterologous genes in Mycobacterium bovis BCG: induction of a cellular response against HIV-1 Nef protein. AB - Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used as a live bacterial vaccine to immunize more than two billion people against tuberculosis. In an attempt to use this vaccinal strain as a vehicle for protective antigens, the human immunodeficiency virus type 1 gene encoding the Nef protein was cloned in a mycobacteria-Escherichia coli shuttle plasmid and transferred into BCG. The nef gene was expressed under the control of an expression cassette carrying the promoter of the groES/groEL1 operon from Streptomyces albus and a synthetic ribosome-binding site. Lymph node cells from mice immunized with BCG-nef proliferated vigorously in response to purified Nef protein. This first report of a proliferative response suggests that recombinant BCG strains may be used to immunize against pathogens for which T-cell-mediated responses are important for protection. PMID- 1756982 TI - Molecular analysis of the dmpM gene encoding an O-demethyl puromycin O methyltransferase from Streptomyces alboniger. AB - The nucleotide (nt) sequence of a 1332-bp fragment of Streptomyces alboniger DNA containing the gene (dmpM), which encodes an O-demethyl puromycin O methyltransferase (DMPM), has been determined. The dmpM gene contains a 1131-nt open reading frame which encodes a polypeptide of Mr 40,303; this is consistent with the 44 +/- 2.5- and 160-kDa sizes of the DMPM monomer and its native form, respectively. The ATG start codon of dmpM is 50 bp downstream from the coding sequence of the gene (pac), which determines a puromycin N-acetyltransferase. S1 mapping experiments indicate that pac and dmpM are transcribed on a single transcript, which ends at least 500 nt downstream from the dmpM stop codon. The deduced amino acid sequence of DMPM shows significant similarities to those of a hydroxyindole O-methyltransferase, which is involved in the biosynthesis of melatonin by bovine pineal glands [Ishida et al., J. Biol. Chem. 262 (1987) 2895 2899], a hydroxyneurosporene methyltransferase, which is involved in carotenoid biosynthesis in the purple nonsulfur bacterium, Rhodobacter capsulatus [Armstrong et al., Mol. Gen. Genet. 216 (1989) 254-268] and two O-methyltransferases of the tetracenomycin biosynthesis pathway from Streptomyces glaucescens. PMID- 1756983 TI - Sequence and linkage analysis of the Coxiella burnetii citrate synthase-encoding gene. AB - The nucleotide (nt) sequence of the Coxiella burnetii citrate synthase-encoding gene (gltA), previously cloned in Escherichia coli, was determined. The nt sequence analysis revealed an open reading frame (ORF) of 1290 bp capable of coding for a protein of 430 amino acids (aa) with a deduced Mr of 48,633. Preceding an ATG start codon, a possible transcription start point (tsp) with homology to the E. coli promoter consensus was detected. A poly-purine-rich region occurred immediately upstream from the gltA reading frame and potentially serves as a ribosome-binding site. Additionally, a G + C-rich region of dyad symmetry 3' to the translational stop codon was found that could possibly function as a Rho-independent transcriptional termination signal. A large, nearly perfect, inverted repeat was identified upstream from the gltA tsp and was shown by Southern analysis to be present in multiple copies in the C. burnetii genome. The deduced aa sequence of C. burnetii GltA was optimally aligned with enzymes from various prokaryotic sources and one eukaryotic source (pig heart). Using perfect aa identity, the C. burnetii enzyme demonstrated the greatest homology with GltA from Acinetobacter anitratum (65%). Although only 26% aa identity was seen with the pig heart enzyme, many of the residues identified in ligand binding appear to be conserved. Sequencing studies of a region centered approx. 5.6 kb upstream from gltA revealed an ORF read with opposite polarity that encodes a peptide highly homologous to the C terminus of the flavoprotein subunit of E. coli succinate dehydrogenase. This report represents the first nt sequence analysis of a gene of known function from the obligate intracellular parasite, C. burnetii. PMID- 1756984 TI - Growth-phase-dependent induction of 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase in the cyanobacterium Synechococcus sp. PCC7942. AB - In most cyanobacteria, the only known pathway for oxidation of stored carbohydrate in the dark or under energy-limiting conditions is the hexose monophosphate shunt. To determine whether the increased use of the shunt under these conditions derives from an increase in the activity level of the respective enzymes, we measured the effect of growth phase during the growth of batch cultures of Synechococcus sp. strain PCC7942 on the specific activity of 6 phosphogluconate dehydrogenase (6PGD) and glucose 6-phosphate dehydrogenase. The specific activities were constant during the exponential growth phase of the culture, but they increased about fivefold during the transition into stationary phase. As an approach to determining the level of expression at which the growth phase-dependent regulation of 6PGD level is exerted, we constructed operon and gene fusions between the gnd gene, which encodes 6PGD, and the Escherichia coli lacZ gene, which encodes beta-galactosidase (beta Gal). Strains harboring the fusions integrated into the cyanobacterial chromosome were prepared, and the growth-phase dependence of beta Gal level was determined. The specific activity of beta Gal in cultures of both types of fusion strains increased during the transition into stationary phase, indicating that the growth-phase-dependent regulation is on the gnd mRNA level. Characterization of the growth-phase dependent induction of 6PGD in strains carrying differing amounts of DNA upstream from the gnd structural gene led to the localization of the promoter and the regulatory site on the restriction map of the gene, whose sequence has previously been determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1756985 TI - The direct cloning of the yeast genome using the gap-filling method and the complete physical mapping of Saccharomyces cerevisiae chromosome VI. AB - The ordered clone library of chromosome VI of Saccharomyces cerevisiae has been constructed by Olson et al. [Proc. Natl. Acad. Sci. USA 83 (1986) 7826-7830, and personal communication]. It is composed of four contiguous stretches from the chromosome, each of 40-70 kb. There remained three gaps of unknown length between these four contigs. We applied the 'gap-repair' method to clone these three gap regions directly from the yeast chromosome. All three gap regions, ranging from 7 to 22 kb, were successfully cloned without any structural changes. Together with these gap regions, a precise physical map of EcoRI and HindIII sites was constructed over the 230-kb fragment which covers most of chromosome VI except for two telomeres. PMID- 1756986 TI - Cloning and expression in Saccharomyces cerevisiae of the NAD(P)H-dependent xylose reductase-encoding gene (XYL1) from the xylose-assimilating yeast Pichia stipitis. AB - The XYL1 gene of the yeast Pichia stipitis has been isolated from a genomic library using a specific cDNA probe, and its nucleotide (nt) sequence has been determined. In the 5' noncoding region of the P. stipitis XYL1 gene a TATAAA element (known to be necessary for transcription initiation in most yeast genes) is found at nt -81, and two CCAAT recognition motifs (often referred to as the CCAAT box) are present at nt -146 and -106. The XYL1 encodes a polypeptide of 35,927 Da that constitutes a NADH/NADPH-dependent xylose reductase (XR). The enzyme is part of the xylose-xylulose pathway that is absent or only weakly expressed in Saccharomyces cerevisiae. Extensive homology is found to the N terminus of the XR of Pachysolen tannophilus and Candida shehatae. None of the known cofactor binding domains found in many NAD-dependent dehydrogenases are present in the protein. Transformants of S. cerevisiae containing XYL1 of P. stipitis synthesize an active XR. Fusion of XYL1 with the prokaryotic tac promoter leads to a gene that can be expressed in S. cerevisiae and Escherichia coli. PMID- 1756987 TI - Replicative transformation of the filamentous fungus Ashbya gossypii with plasmids containing Saccharomyces cerevisiae ARS elements. AB - We have developed a transformation system for the filamentous ascomycete fungus Ashbya gossypii. Mycelial protoplasts were transformed to geneticin-resistance with plasmids containing the Escherichia coli kanamycin-resistance gene as a selectable marker and autonomously replicating sequences (ARS) from Saccharomyces cerevisiae (ARS1, 2 mu ARS). Transformation frequencies of up to 63 transformants per microgram of plasmid DNA were obtained. The transformants were unstable under nonselective conditions. Southern analysis of DNA separated by conventional and pulsed-field-gel electrophoresis showed that the transforming DNA was present as autonomously replicating plasmid. Plasmid integration into chromosomal DNA was not detected. We concluded that the S. cerevisiae ARS elements are functional in A. gossypii, since vectors lacking such elements did not yield transformants. PMID- 1756988 TI - Differences in susceptibility between crystallins and non-lenticular proteins to copper and H2O2-mediated peptide bond cleavage. AB - The relative susceptibilities of lenticular proteins (alpha, beta and gamma crystallins) and a number of proteins of non-lenticular origin, to hydroxyl radical-mediated peptide bond cleavage were compared. The non-lenticular proteins (bovine serum albumin, ovalbumin, alcohol dehydrogenase, lysozyme, thyroglobulin, beta-amylase, haemoglobin and carbonic anhydrase) were readily cleaved into acid soluble fragments following 5 hours treatment with copper ions and hydrogen peroxide. In contrast the crystallins were almost totally unaffected by similar treatment. When alpha-crystallin was pre-treated with acid or cleaved into large fragments with cyanogen bromide it became susceptible to hydroxyl radical attack, yet heating the protein did not diminish its resistance. It is suggested that the resistance of alpha-crystallin to the copper/peroxide-mediated fragmentation may be dependent on the conformation of the protein. PMID- 1756989 TI - Induction and rejoining of DNA single-strand breaks in relation to cellular growth in human cells exposed to three hydroperoxides at 0 degrees C and 37 degrees C. AB - There was a 5-fold increase in cytotoxicity for cumene hydroperoxide, 10-fold for tert-butyl hydroperoxide and 25-fold for hydrogen peroxide, under metabolizing conditions (37 degrees C) in comparison to nonmetabolizing conditions (0 degrees C), when human P31 cells were exposed for 60 min. The induction of DNA single strand breaks correlated poorly with cytotoxicity. Hydrogen peroxide was by far the most effective agent inducing single-strand breaks irrespective of temperature. Cumene hydroperoxide produced fewer strand breaks than tert-butyl hydroperoxide despite its greater cytotoxicity at either 37 degrees C or at 0 degrees C. The pattern of single-strand break induction did not change with temperature. The number of breaks, however, increased when the cells were exposed at 37 degrees C. The pattern of rejoining was similar for hydrogen peroxide- and tert-butyl hydroperoxide-induced breaks at both temperatures whereas the rejoining of cumene hydroperoxide-induced breaks deviated somewhat from this pattern. The results indicate that there is no clear-cut relationship between induction of DNA single-strand breaks and cytotoxicity after hydroperoxide exposure. PMID- 1756990 TI - Calcium antagonists prevent monocyte and endothelial cell-induced modification of low density lipoproteins. AB - Low density lipoprotein (LDL) incubated in the presence of the calcium antagonists verapamil, nifedipine and flunarizine were more resistant than control LDL to human monocyte- or endothelial cell-induced modification, as assessed by electrophoretic mobility in agarose gel, thiobarbituric acid reactive substance content, and degradation by J774 macrophages. The efficiency of the drugs was: flunarizine greater than nifedipine greater than verapamil. Moreover, a 24 h preculture with calcium antagonists significantly impaired the ability of cells to modify LDL in the absence of the drugs. All the studied drugs also inhibited copper-induced autooxidation of LDL. None of the studied calcium antagonists, at concentrations up to 10(-4) M, significantly reacted with free radicals as assessed by the 1,1-diphenyl-2-picrylhydrazyl test. It is suggested that such a protective effect of calcium antagonists against LDL peroxidation could play a role in the previously reported antiatherogenic effect of these drugs. PMID- 1756991 TI - Interruption of pregnancy: motives, attitudes and contraceptive use. Interviews before abortion, at a family planning clinic, Rome. AB - Since 1978 when the law on legal abortion came into force, approximately 35% of all pregnancies in Italy have ended in abortion (illegal abortions excluded). Presently about 25% (national average) of the women who interrupt pregnancy get their medical certificate at a family planning clinic. The general aim of the present study was to describe women's situation on the occasion of their first visit to the family planning clinic, their problems and their motives to abortion. Over a period of 6 months, 65 women were interviewed during their visit to a family planning clinic before interruption of their pregnancy. A semistructured questionnaire was used concerning their motives for interruption of pregnancy, contraceptive habits, their attitudes to abortion and the male partner's participation. The women arrived in an early stage of the pregnancy, 46 women said that they had considered the possibility to interrupt the pregnancy almost at the same time as they got the message that they were pregnant. Twenty eight women had already a previous abortion, the use of contraceptives did not differ among these women and was generally scarce. Twenty-one women said they had been against abortion before their own experience or said they had never believed themselves to be in need of an abortion. PMID- 1756992 TI - Lipid profiles during and after normal pregnancy. AB - Lipid profiles were estimated in two groups of normal healthy women comprising 39 non-pregnant women and 67 pregnant women at 28 and 32 weeks gestation and 6 weeks after delivery. Triglycerides, total, HDL and LDL cholesterols were high during pregnancy. Except for LDL cholesterols which remained constant, all the above decreased at 6/52 postnatally, but levels were still above those of normal non pregnant women. Compared to the later, the atherogenic index, LDL/HDL cholesterol ratio was unchanged during pregnancy but significantly increased at 6/52 postnatally. These results may suggest that while total lipid levels increase during pregnancy, this is balanced by an even distribution of the lipoprotein fractions. After delivery, though lipid levels had decreased, the decrease in HDL cholesterol and increase in LDL cholesterol caused unfavourable changes in lipid lipoprotein ratios. These changes may be due to the change in metabolism of the pregnant women as well as diet during and after pregnancy. PMID- 1756993 TI - Loss of growth hormone responsiveness to normal physiological stimuli during pregnancy. AB - The response of pituitary GH to acute hyperglycaemia induced by 75 g oral glucose load in 73 pregnant women at various stages of gestation was examined. According to the age of gestation, patients were grouped into three groups: less than 20 weeks, between 20-30 and more than 30 weeks. Plasma glucose, GH and C-peptide were measured at fasting and then at 30, 60, 120 and 180 min following the glucose load. There was a significant increase in plasma GH concentration with weeks of gestation. The results also showed a loss of the normal physiological suppressive effects of hyperglycaemia on GH secretion in tests performed after 20 weeks of gestation. Only in tests performed before 20 weeks, there was a significant negative correlation between plasma glucose and GH values. These findings are consistent with recent reports suggesting an almost complete suppression of pituitary GH secretion by a placental variant of GH. These changes in the dynamics of GH secretion suggest that, in pregnancy, GH plays a more significant role than was previously thought. PMID- 1756994 TI - Measurements of the fetal liver size, hormonal level and pregnancy outcome. AB - To further deepen the understanding of growth and development of a fetal liver, we measured sizes of 108 fetal livers using ultrasound and compared them with levels of urinary estriol excretion and human placental lactogen in the sera of their mothers. The present data suggested that growth and development of a fetal liver correlated with the levels of these hormones. Measurements of the fetal liver sizes also possibly indicate the perinatal outcome. PMID- 1756995 TI - Tumor necrosis factor alpha is elevated in the peritoneal fluid from women with ruptured ectopic pregnancies. AB - The purpose of this study was to determine whether exposure of the peritoneum to fetal tissue is associated with elevated tumor necrosis factor alpha (TNF alpha) levels in the peritoneal cavity. We measured TNF alpha levels in the peritoneal fluids and serum from women with ruptured ectopic, unruptured ectopic and intrauterine pregnancies, as well as nonpregnant women undergoing tubal ligation. The results showed that patients with ruptured ectopic pregnancies were more likely to have TNF alpha levels in the peritoneal fluid greater than 40 units/ml (68%), compared with women with unruptured ectopic or intrauterine pregnancies (21%) (p less than 0.05, Fisher exact test). No elevation of peritoneal fluid TNF alpha levels was found in nonpregnant patients. Because TNF alpha is primarily a product of activated macrophages, it is likely that elevated TNF alpha levels in the peritoneal fluid of women with ruptured ectopic pregnancies reflects activation of peritoneal macrophages. PMID- 1756996 TI - Antithromboxane drug in the treatment of preeclampsia. AB - In this study, we present our initial trials in the treatment of 6 cases of severe preeclampsia with thromboxane synthetase inhibitor (OKY-046). Following the treatment with OKY-046, maternal systolic blood pressure decreased significantly and umbilical artery waveforms were normalized. These data suggest that thromboxane synthetase inhibition might have a beneficial effect on preeclampsia. PMID- 1756997 TI - Perinatal outcome in fetuses with loss of end-diastolic blood flow velocities in the descending aorta and/or umbilical arteries. AB - Continuous- and pulsed-wave Doppler velocimetry was used as an additional method of antenatal surveillance in high-risk pregnancy care. During a 30-month period with 4,169 deliveries 226 patients (5.4%) with complicated pregnancies (intrauterine growth retardation, diabetes, hypertension) were investigated. The results had only marginal influence on obstetrical management. In 38 fetuses absence of end-diastolic blood flow velocities (AEDF) was detected in the descending fetal aorta and/or umbilical arteries. Mean birth weight of these fetuses was 1,441 +/- (SD) 690 g at a mean gestational age of 31.8 +/- 6.8 weeks at birth. Twenty fetuses (53%) were growth-retarded (less than 3rd centile). Six fetuses died in utero and 7 during the perinatal period (34% mortality). There was a significant deterioration of perinatal outcome with AEDF in the umbilical arteries at the last antenatal Doppler scan. With AEDF in the descending fetal aorta the Doppler parameter Vmean and with AEDF in the umbilical arteries the pulsatility index yielded additional prognostic information. Doppler velocimetry of the fetal and umbilical vascular system could be of additional value for antenatal surveillance in high-risk pregnancies. PMID- 1756998 TI - Effect of continuous lumbar epidural anaesthesia during labour on fetal transcutaneous carbon dioxide. AB - The effect of epidural anaesthesia during labour on fetal transcutaneous carbon dioxide (tcPCO2) was observed on 27 fetuses. Our results show that in the course of epidural anaesthesia there is an increase in fetal tcPCO2. We can see a slight increase even before administering the test dose, while preparatory measures are undertaken for the epidural anaesthesia. After administering the test dose and after giving the main dose there is a further increase in fetal tcPCO2, which continues for up to 30 min after the main dose has been given. The results suggest that it is important to consider any pathological conditions in the fetus, so as to avoid the possibility of additionally endangering the fetus during epidural anaesthesia. PMID- 1756999 TI - Perineal ultrasonography in women with stress incontinence and controls: the role of the pelvic floor muscles. AB - With a curved array real-time ultrasound scanning machine and the probe placed sagitally onto the vulva, symphysis, bladder, urethra and the pelvic floor can be visualized in one frame. With this technique we studied 10 women with stress incontinence and 10 control women. In both groups active contraction of the pelvic floor resulted in a similar elevation of the urethrovesical junction (UVJ). During Valsalva maneuver an equal descent of the UVJ was found in patients and controls. During coughing a significant descent of the UVJ only occurred in the patient group. This suggests that women with stress incontinence are capable of operating the pelvic floor muscles but do not use them adequately during a cough. PMID- 1757000 TI - Increased nuclear damage by high linear energy transfer radioisotopes applicable for radiodirected therapy against radiologic malignancies. AB - High linear energy transfer radioisotopes carried by appropriate agents have been proposed for receptor-directed radiotherapy. Two such classes of isotopes are Auger electron and alpha-emitting nuclides. To determine the relative cytotoxicity and nuclear damage to cells produced by these two classes of nuclides, we compared bromine-80m (80mBr), an Auger-electron-emitting radionuclide with a 4.4-hour half-life, with bismuth-212 (212Bi), an alpha emitter with a 1-hour half-life. Because of the short path length of the Auger electrons, 80mBr was radiotoxic only when incorporated into DNA, such as in the form of [80mBr]bromodeoxyuridine ([80mBr]BrUdR). Both agents induced linear increases in chromosome aberration frequency, however, [80mBr]BrUdR caused multiple aberrations including the shattering of parts of the chromosomes. While, in contrast, a 2-hour exposure of cells to 212Bi, chelated to DTPA, a form which does not enter the cell, induced much less extensive chromosome damage. Exposure to equivalent activities of Auger electrons or alpha-particles results in 5 times more damage in Auger-electron-exposed cells. However, estimates of dose suggest they are equally toxic. Unlike Auger electrons, alpha-particles did not need to be in as close proximity to the DNA to have clastogenic and radiotoxic effects. PMID- 1757001 TI - Immunohistochemical localization of blood group substances in normal and neoplastic endometrial tissues--with special reference to type 1 core chain expression. AB - Immunohistochemical stainings were performed to observe the expression of the blood group antigens (A, B, H, Lewisa, Lewisb) and lactoseries type 1 core chain in normal and neoplastic endometrial tissues using a panel of monoclonal antibodies. The results indicated that normal endometrium mostly lacked the expression of these sugar structures. In endometrial carcinoma, the expression of H, Lewisa, Lewisb was evident and type 1 core chain was observed only after neuraminidase pretreatment. These data indicated that type 1 core chains were newly synthesized according to malignant transformations in endometrial tissues and they were partially fucosylated and partially sialylated. PMID- 1757002 TI - Pregnancy in cyclic neutropenia. AB - We present a patient with cyclic neutropenia who had two successful pregnancies during which the disease improved. Following one of the deliveries severe endometritis and wound dehiscence of the episiotomy developed and neonatal pemphigoid was seen. PMID- 1757003 TI - Heterotopic striated muscle in the myometrium in a patient with myoma uteri. AB - Heterotopic striated muscle tissue was found in the myometrium of a 50-year-old Japanese woman with myoma uteri. It is suggested that the tissue originated in a differentiation of stromal cells in the myometrium. PMID- 1757004 TI - [A new classification of distal radius fractures and corresponding treatment methods]. AB - Based on previously published reports on fractures of the distal radius and on the analysis of 400 fresh fractures treated in two accident hospitals affiliated with our university hospital, we propose a new classification as shown in Table 2. This new classification includes a type of combined Chauffeur-Barton fracture which has never been described before. Each type of fracture of the distal radius requires a specific treatment as shown in Fig. 1. PMID- 1757005 TI - [Diagnosis of torsion malposition of the radius and ulna after healed distal fracture]. AB - Assessing radial and ulnar rotational deformities quantitatively by routine diagnosis after healed distal forearm fractures is very difficult. A method to obtain information about direction and graduation of malrotation is described. This method is based on discovering topographic changes of skeletal points by CT. Rotational angles of intact forearm bones are measured on anatomic specimen and in vivo using epiphyseal and diaphyseal axes of the radius and the ulna. Normal rotation of intact forearm bones varies in a specific manner. The radius presents less variations than the ulna. A morphological index of radial and ulnar rotation is not given because of the great individuality of diaphyseal rotation. Both radii of a single individuum show a very small rotational difference. Therefore a verification of malrotation is indicated by comparison to the intact opposite radius. Higher rotational graduations on the left side have to be noted. PMID- 1757006 TI - [Results and analysis of poor results after conservative therapy of distal radius fracture]. AB - The authors report on the results of a follow-up study of 120 conservatively treated distal radius fractures. Follow-up averaged 35 months (25 to 48 months). The quality of initial reduction has a crucial impact on the final outcome. 87 fractures showed nearly perfect anatomical reduction, of these, 48 resulted in excellent, 16 in good, 15 in satisfactory, and 8 in poor final anatomical outcomes. In comparison, in 33 fractures with unsuccessful initial reduction, only two cases gave excellent and 12 cases good results (42%); 11 fractures were considered satisfactory and 8 poor. The necessity of a second reduction was significantly lower in the first group of initially well-reduced fractures when compared to the second group: 8 (9.2%) to 14 (42.4%) respectively. Evaluation of the functional outcome according to the Sarmiento scheme showed a strong correlation between the AO fracture classification and the final outcome. In group A fractures, 78% gave excellent or good, 22% satisfactory or bad results. Type B fractures gave 82% excellent or good and 18% satisfactory or poor results. In group C, only 50% reached excellent or good results, the C 3 fractures having the worst prognosis, achieving excellent or good results in only 20% of the cases. Regression analysis demonstrated a significant correlation between anatomical and functional outcome. PMID- 1757007 TI - [Value of plate osteosynthesis in treatment of radius fractures at a typical site]. AB - In the past, distal radius fractures tended to be treated conservatively. Recently, however, unsatisfactory anatomical and functional results have led to an increase in their surgical treatment. Our preferred method of treatment has been percutaneous pin fixation after closed reduction. In our opinion, open reduction and internal fixation with an A0-plate is indicated for Smith fractures (B3 A0-classification), and for any fractures which cannot be ideally reduced (usually C1 to C3 fractures). From 1972 until 1989, 84 patients with distal radius fractures underwent surgical treatment in the Unfallkrankenhaus Salzburg. The procedure was usually performed under brachial plexus or Bier block, and we preferred a palmarly positioned plate for internal fixation. Follow-up of 42 patients showed good results, the functional and subjective results earning higher marks than the X-ray findings. PMID- 1757008 TI - [Secondary arthrosis of the wrist joint in malposition of healed and uncorrected distal radius fracture]. AB - The authors report on long-term results of thirty-five unreduced distal radius fractures with malunion. The mean observation period was 11.5 years (5 to 45 years). It was found malalignment of the carpal articular surface of the radius with a resulting decrease in range of motion of the wrist, well tolerated by the patients and apparently not very painful. Much more evident was pain and decreased motion in the distal radio-ulnar joint for pronation and supination, which paralleled the extent of osteoarthrosis of this joint. This reduced forearm rotation was due to shortening of the radius, leading to incongruency and even dislocation of the distal radio-ulnar joint. PMID- 1757009 TI - [Distal radio-ulnar arthrodesis and Kapandji ulna segment resection in treatment of limited forearm rotation]. AB - Between 1986 and 1990 distal radioulnar arthrodesis with segment resection of the distal ulna (Sauve-Kapandji Operation) was performed in 31 patients with posttraumatic changes of the distal radioulnar joint; 26 patients could be examined after 10 to 44 months. At the time of examination, all patients had bony fusion between distal radius and ulna; forearm rotation improved by 60.5%, 55% of the patients had significant pain relief. Grip strength also improved postoperatively, though never reaching values of the healthy hand. Two patients developed a bony regeneration, which was successfully reoperated upon in one case, 81% of the patients reported an improved wrist function. PMID- 1757010 TI - [Experimental studies of forces on the radiocarpal joint in minus deviation of the ulna]. AB - The length of the radius was experimentally altered with respect to the distal end of the ulna. Pressure levels at several points in the wrist were measured simultaneously. Lengthening of the radius leads to an increased pressure between the distal radius and scaphoid and between the distal radius and lunate. PMID- 1757011 TI - [Pseudarthrosis of the capitate bone with special reference to ligamentous stabilization]. AB - Non-union of the capitate is rare. So far, six cases of non-union have been reported. The authors add a new case report, involving a 29-year old tobacco worker with a typical history. The length of the capitate was restored by corticocancellous bone grafting. The mechanism by which non-union occurs is discussed, showing that the uninjured palmar V ligament in the wrist is responsible. PMID- 1757012 TI - [Protective microvascular anastomosis in transverse rectus abdominis myocutaneous flap for breast reconstruction]. AB - Given favorable conditions, breast reconstruction with the TRAM-flap yields the best results. However, because of limited blood flow in the flap after dissection, partial flap necrosis occurs frequently. To avoid this, a bipedicled flap has been used. Although complications are substantially fewer, the necessity for improvement of flap perfusion still remains. We have carried out breast reconstruction using the TRAM-flap in 66 cases to date. In two of these, the vascular system of the deep inferior epigastric artery and vein were successfully anastomosed (end-to-side) with the thoracodorsal vessels. Although this technique was more time consuming and entailed cooling, it has proven to adequately protect the flap. Careful dissection and preservation of the deep inferior epigastric vessels is mandatory. PMID- 1757013 TI - [Results of sex change operations in 30 transsexual patients: psychosocial and sexual adaptation--surgical complications]. AB - Ten male and twenty female transsexual patients who had undergone sex reassignment surgery were followed-up with regard to postoperative complications, partner and sexual interaction and their overall ability to cope with their new situation. Despite unsatisfactory functional results, social and sexual life improved after sex reassignment surgery. PMID- 1757014 TI - [Periodontal and esthetic aspects of orthodontic frontal space closure--results of a long-term study]. AB - In this study follow-up results of patients are presented, who have been treated in cases of missing incisors by orthodontic space closure. The statements of clinical examinations, casts, intra- and extraoral photographies, x-rays, periodontal examinations and questionnaires pointed out, that the abnormal position of the moved teeth do not interfere with the periodontal tissues. Should the occasion arise of correction by crowns or by grinding, the patients consider the abnormal positioned teeth as esthetical. PMID- 1757015 TI - [Long-term results of treatment of distal occlusion with the function regulator]. AB - 88 children with a class II/1 malocclusion were analyzed cephalometrically concerning dental and skeletal changes through a period of approximately 10 years. 50 patients were treated with function regulators and 38 cases served as a control group. At the beginning, there were no significant differences between the groups studied but in the end, the patients at the age of approximately 17 treated with function regulators showed a stronger mandibular advancement of 4 4.5 mm. PMID- 1757016 TI - [The value of electronic axiography in clinical functional diagnosis]. AB - Recent years have brought an increasing number of electronic jaw-tracking devices for instrumental analysis on the market. However sophisticated they may be, their diagnostic value for temporomandibular diseases is not well supported by scientific evidence. On the other hand, "manual examination"--a very refined diagnostic means acknowledged by orthopedians and adapted to the properties of the TMJ--yields a more reliable diagnosis which fits well to MRT data. We were hereby solicited to compare the information gained by jaw-tracking and manual examination. It was found that the recorded condylar movements gave no additional, diagnostically relevant insight that went beyond the manual examination. Nevertheless, the accuracy of jaw-tracking, with regard to the visualisation of internal derangements of the TMJ, was enhanced by the techniques of manual examination. PMID- 1757017 TI - [Gnathographic study of mandibular borderline movements and chewing patterns before and after surgical dysgnathia correction in retrognathism and prognathism]. AB - Chewing patterns and longitudinal border movements of 16 patients with severe dysgnathia were examined preoperatively and up to 12 months postoperatively by means of sirognathographic records of surgical-orthodontic treatment results. Patients with a skeletal class-III malocclusion showed an increased range of movement compared to the preoperative situation, after a surgical mandibular setback performed by wire osteosynthesis, followed by an intermaxillary immobilisation of 6 weeks. Patients with a skeletal class-II malocclusion showed a considerably limited range of movement during the first postoperative registration after a surgical mandibular advancement. The preoperative situation had not been fully achieved even after 12 months. The postoperative sirognathographic records present distinct differences in functional adaptation between surgical mandibular advancement and mandibular setback. PMID- 1757018 TI - [Long-term results after genioplasty]. AB - The serial records of 21 patients were analyzed to study the stability of genioplasty performed in the course of orthognatic surgery and to describe its effect on the soft tissue profile. A pre-operative and a post-operative cephalogram as well as a cephalogram one year after surgery of each patient were available. Sagital correction of the chin from 16.5 mm advancement to 1.1 mm reduction and vertical movements between 4.8 mm lengthening and 9.3 mm shortening remained nearly unchanged during the control period. No post-operative movements of the chin fragment were observed except for minor resorptions that can be attributed to an osseous remodelling and rounding of sharp edges. In cases of a long face syndrome a bone apposition from 1 mm to 5.5 mm appeared at the lower edge of the chin. The average of sagittal soft tissue change in relation to the correction of the bony chin was 71%. The individual values ranged from 4% to 145% and the standard error of the estimate was 3 mm. Therefore the planning of the soft tissue profile is rather unreliable. A genioplasty performed with rigid fixation by compression screws or mini plates, preservation of vascular supply and re-fixation of the soft tissue of the chin results in accurately predictable and stable bony contours. On the other hand, the planning of surgery procedures related to the soft tissue profile is--if at all possible--very insecure. PMID- 1757019 TI - [Comparative study of the accuracy of localizing cephalometric reference points in using digital and conventional imaging technique]. AB - The purpose of this study was to present possible advantages of digital luminescence radiography for cephalometry. Conventional and digitalized lateral headfilms were compared and evaluated. The first impression of an improved simultaneous presentation of bony structures and soft tissue profile in digital x rays was statistically verified. A significant difference in identification of several reference points was proven by means of the F-test. The superior results of the digital luminescence radiography were evaluated in comparison with xeroradiography and experimental postdigitalization of conventional x-rays. PMID- 1757020 TI - [The accuracy of soft tissue profile prediction with the "Dentofacial Planner" in skeletal prognathism]. AB - 30 pre- and postoperative lateral cephalograms of patients with mandibular prognathism are used to evaluate the soft tissue profile prognosis given by the "dentofacial planner". As a result, the horizontal displacement of SLS (sulcus labrale superius) and Pg' (soft tissue pogion) in patients with a normal vertical dimension and additional LMF (labiomental fold) in persons with a marked overbite are calculated well. The horizontal changes of the other points analyzed as well as all vertical changes are not predicted satisfactorily in the momentary version 4.22 A (febr. 1989), which will be improved by the company. PMID- 1757021 TI - [Head posture in lateral roentgen image]. AB - A cervico-cephalometric examination of 61 yet untreated orthodontic patients was performed in order to analyze differences in head posture between standardized cephalograms and lateral cephalograms taken in natural head position. Additional x-rays were taken in extreme flexion and extention of the head in 48 patients examining the mobility of the upper cervical spine. Finding partly large differences in cranio-vertical and cranio-cervical parameters between the two methods of registration it could be shown, that head posture on the average was more proclined in natural than in fixed standardized position. Subjects with class III malocclusion tended to a more extended head posture relatively to those with class I or class II malocclusion. Judging the atlas position with regard to the functional mobility of the upper cervical spine, a superior and inferior atlas position was not thought to be a pathologic fixed malposition. PMID- 1757022 TI - [Bonding strength of brackets with and without silane coating]. AB - This study was undertaken to show that a silane treated bracket base can provide a better bonding to the enamel than conventional bonding bases commercially available. Five different types of metal brackets, each with different retentive properties, were tested. 20 brackets of each type were used, half of them silanated with a special silicoater treatment. The brackets were bonded to the surface of the teeth with Concise Enamel Bond and were then tested to failure in an Instron testing machine after 28 days. The following conclusions can be drawn from the study: 1. Silane-coated bracket bases demonstrated a higher bonding strength than the conventional bases, 2. silane treatment of plain bases is an effective method for the bonding of brackets to teeth, similiar to non-silane boated brackets with additional mechanical retentive devices. PMID- 1757023 TI - [Current state of implantation of flexible intraocular lenses]. AB - Two main arguments have stimulated the development of hydrogel and silicone lenses: flexibility allows folding and thus insertion through a small incision, and inertness promises excellent biocompatibility, possibly surpassing that of PMMA. However, as long-term performance remains to be established, these implants cannot yet be considered a routine alternative. Clinical studies are mandatory to document their advantages and any disadvantages, especially as few of the reports already published on experience with such lenses do not give an objective picture of the current status: the surgical techniques used and the observation criteria applied differ and were sometimes inappropriate. In addition, the series are too small and the follow-up studies too short to allow valid conclusions. In this paper, following the description of the materials and designs and of the implantation techniques available for flexible lenses, a review of the pertinent literature and the author's own experiences is reported. This is based on 800 implantations performed over a period of 4 years. Monobloc designs with flange haptics (IOGEL, STAAR) have been found to perform best. The Faulkner folder has proved to be optimal, allowing for easy and atraumatic folding and insertion. Within the eye, the lens is safely guided and released. Bag placement of appropriately styled lens models is strongly recommended, since sulcus-placed lenses have sometimes shown either iris bulging or decentration and windshield wiper or propeller phenomena. The capsular edge should be smooth and the capsular opening well centered and round in order to guarantee stable fixation and symmetrical compression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757024 TI - [Intraocular antibiotic administration for prevention of fibrin reaction after extracapsular cataract extraction? A randomized double-blind study]. AB - Postoperative fibrinoid reactions are regarded as a localized form of endophthalmitis caused by microbial contamination of the capsular bag during intraocular lens implantation. The incidence of early fibrinoid reactions within the first 6 postoperative days following extracapsular cataract extraction was examined after intraocular administration of antibiotics vs placebo. In a double blind randomized trial, 2 mg cefamandol or a placebo was administered in a 0.4-ml volume at the end of the operation. A group of 28 patients received the antibiotic (mean age 74.6 years; 15 f, 13 m), while 33 patients received the placebo (mean age 72,1 years; 21 f, 12 m). Fibrinoid reactions were observed in 8 out of 61 patients during the first 6 postoperative days. There was no significant difference between the antibiotic group and the placebo group (P = 0.31). We were unable to reduce the incidence of fibrinoid reactions although we had selected a broad-spectrum cephalosporin for antibiotic treatment. The results give rise to the suspicion that most of the early postoperative fibrinoid reactions we observed were not caused by contamination with bacteria of low pathogenicity. PMID- 1757025 TI - [Absence of cataractogenic effect of lovastatin (Mevinacor) so far]. AB - Lovastatin is an inhibitor of HMG-Co A reductase, a key enzyme in cholesterol biosynthesis. It is of therapeutic value in hypercholesterolemia type IIa and leads to decreased levels of low-density lipoproteins in serum. Treatment with high doses of lovastatin has been reported to induce cataract formation in dogs. The goal of the ongoing prospective clinical study is to evaluate whether cataract formation is caused in humans by therapeutic doses of lovastatin. So far 28 patients (average age 44 years) suffering from hypercholsterolemia have entered the study. Besides thorough slit-lamp investigations in all patients, best corrected visual acuity and contrast sensitivity for five different spatial frequencies were measured. A reduction in contrast sensitivity is a sensitive indicator for opacities of lens and cornea. During a mean follow-up of 37 weeks (range 5-62 weeks) with a mean total dose of 15 g (range 2-26 g), no cataract formation or decreased contrast sensitivity has so far been observed. PMID- 1757026 TI - [PDGF-induced calcium increase in cultivated epithelial cells in the cattle lens]. AB - Platelet-derived growth factor (PDGF) is one of numerous growth factors regulating development of the ocular lens and its component parts. Although little is known about its site of action on the cell and the mechanisms of this confirmed mitogenic action, a close connection has been assumed between the influence of PDGF on both the lens epithelium and intracellular calcium homeostasis. The present study therefore examined the influence of PDGF on the concentration of intracellular free calcium [( Ca2+]i) in primary cultivated bovine epithelial cells. A dose-dependent [Ca2+]i increase of up to 300% followed stimulation with PDGF (5-50 ng/ml) in a medium containing Ca2+. [Ca2+]i also rose significantly in Ca(2+)-free medium, indicating mobilization from intracellular storage. PMID- 1757027 TI - [Controlled clinical study of two viscoelastic substances]. AB - Viscoelastic substances in correlation with intraocular hypotony have gained great significance in low-irritation cataract surgery within the last few years. The differences in their chemical properties, and thus in their effect on the eye, formed the grounds for a controlled clinical study comparing sodium hyaluronic acid, representing the group of glucosamine glykanes, and hydroxypropylmethyl cellulose (HPMC), representing the group of cellulose ethers. Two hundred cataract patients, excluding those suffering from diabetes mellitus, glaucoma and severe corneal damage, were examined on the 1st, 2nd and 5th postoperative day, as well as 4 weeks postoperatively. Statistically, no significant differences were found as regards IOP and postoperative anterior chamber irritation. From the economical point of view, methocel (HPMC) should be preferred to sodium hyaluronic acid in routine cataract surgery due to the lower costs. PMID- 1757028 TI - [Retinal lesions after transvitreal use of ultrasound]. AB - Removal of a dislocated natural lens into the vitreous cavity is now performed using vitreous surgery techniques combined with intravitreal phacoemulsification via the pars plana. In contrast to the earlier external surgical approach to luxated lenses, postoperative complications, particularly retinal detachment, are rare. However, retinal damage may occur when ultrasound is used at therapeutic intensities. We therefore examined ultrasound-induced retinal lesions produced in rabbit eyes by treating the retina directly with ultrasound using the type of tip conventionally used for pars plana lensectomy (Fragmatom). Histological evaluation showed that acoustic energy at low intensities led primarily to damage of photoreceptor cell outer and inner segments, which correlated with a discrete pigment reaction visible on ophthalmoscopy. More severe lesions were seen in destruction of the inner retina and resulted in retinal blanching or caused a small retinal break. High energy led to a full-thickness retinal defect with rupture of choroidal vessels and heavy bleeding into the vitreous cavity. Within these lesions the retinal pigment epithelium and Bruch's membrane were also disturbed. Our ophthalmoscopical and histological findings indicate that the mechanism of ultrasound-induced chorio-retinal lesions is not exclusively thermal in nature and differs from other coagulation modalities. PMID- 1757029 TI - [Bilateral chorioretinitis after infection with Yersinia enterocolitica]. AB - We report a case of severe, bilateral panuveitis with disseminated chorioretinis. With systemic steroid therapy the inflammation resolved within 4 weeks, resulting in chorioretinal scarring. Because the agglutination titer against Yersinia enterocolitica type 3 was increased to 6 times over normal, we consider Yersinia to be the most probable cause of the panuveitis. Concomitantly, serology revealed evidence for recent infection with mumps and shigella. Both can cause anterior uveitis. Therefore, we cannot exclude interactions, which may influence the clinical picture. After reviewing the literature we describe for the first time a case of chorioretinits and panuveitis associated with infection by Yersinia. PMID- 1757030 TI - [Humoral immune response to retinal S-antigen in patients with uveitis]. AB - Experimental autoimmune uveoretinitis (EAU) is a predominantly T-cell-mediated autoimmune inflammatory disease of the retina and uveal tract of the eye. Retinal S-antigen, a protein found in retinal photoreceptor cells, is a potent agent for the induction of EAU in susceptible species and strains. Elevated titers of antibody to S-antigen have been reported in patients with different forms of uveitis. Serum samples from 166 patients and 87 healthy blood donors were tested by immunoblotting against human retinal abstract for IgG, IgM and IgA antibodies to S-antigen. Compared to the controls the patient sera showed a higher incidence of S-specific antibodies (17.5% vs 9.2%). No specific correlation between the presence of any type of uveitis and anti-S antibodies has been found (anterior uveitis 15.1%, posterior 19.6%, panuveitis 18.9%). There was a higher incidence especially with IgG antibodies during active disease (19.7% vs 9.2% in controls). The results suggest that since EAU is T-cell mediated, antibodies in humans may be most important as indicators of autoimmunity rather than mediators of the inflammation. As these anti-S antibodies might be induced by disruption and nonspecific inflammation of the retina and uvea alone, an important and difficult question in patients is whether or not these secondary autoimmune response can contribute to the induction of uveitis. PMID- 1757031 TI - [Autosomal dominant hereditary retinopathia pigmentosa with genetic heterogeneity]. AB - There is considerable clinical variability in autosomal dominant retinitis pigmentosa (ADRP). The underlying biochemical defect had remained unknown until recently, so that it was not possible to determine the primary cause(s) of this phenotypic diversity. Recently, different point mutations and base pair deletions have been identified in the rhodopsin gene in a proportion of patients with ADRP, providing convincing evidence for allelic genetic heterogeneity in this disease. We screened a total of 65 patients with ADRP in Germany, Austria, and Switzerland for the presence of the point mutations described recently at codons 58 and 347 in patients in the USA. Our results show that the frequency of point mutations at codon 347 in the patients studied here is about 3%, a figure similar to that found in the USA. The frequency of the mutation at codon 58 seems to be generally low. The identification of patients with point mutations in the rhodopsin gene offers the possibility, for the first time, of studying the correlation between genotype and disease phenotype. PMID- 1757032 TI - [Hemodynamic findings after retinal interventions]. AB - In this study we tried to find out if the hemodynamic results could help us explain why the visual situation after retinal surgery often becomes unsatisfactory despite good anatomical results. Using Ulrich's methods (oculo oscillodynamography), we measured the hemodynamic parameters-especially ciliary perfusion pressure and the volume of blood flow--in 40 patients after retinal surgery. One of our results is remarkable: there is a direct relationship between the amount of scleral buckling and a disturbance in the hemodynamic parameters. Otherwise, we found that hemodynamic disturbances after vitreous surgery (vitrectomy, silicone oil implant or gas) are less dramatic than after buckling methods or in connection with them. Also, the hemodynamic disturbance begins before retinal surgery, obviously according to the stage of ablation: with or without macular involvement and irrespective of the time of retinal detachment. After all we have demonstrated in this study, we have reason to believe that a disharmony in the ocular hemodynamics causes disappointing visual results, often seen after retinal surgery. PMID- 1757033 TI - [Retinal degeneration and embryonal rhabdomyosarcoma of the thorax]. AB - We discuss a paraneoplastic retinopathy in a 6-year-old boy who had an embryonal rhabdomyosarcoma of the thorax. Opacities of the vitreous body, optical atrophy, contracted arteries and changes in the structure of the retina--especially the retinal pigment epithelium--characterized the ophthalmological findings. The asymmetrical localization of the changes makes the differential diagnosis of hereditary retinal dystrophies easier. It is probably an immunological disease caused by an antigenic antibody reaction. PMID- 1757034 TI - [Retinal nerve fiber layer photography in retinal vein occlusion]. AB - In six eyes we found typical signs that could serve as criteria for the differentiation of ischemic from non-ischemic retinal branch vein occlusion. Perimetry showed a mean defect (in the affected area) of more than 10 dB in eyes with defects in the retinal nerve fiber layer in contrast with 5 dB on one eye without nerve fiber defects. Secondly, fluorescein angiography showed ischemic areas in all eyes examined with localized defects in the photographs of the retinal nerve fiber layer. Damage of the retinal nerve fiber layer was observed before capillary obliteration could be detected by fluorescein angiography. Thirdly, semiquantitative optic disc morphometry demonstrated that using the difference between pallor and excavation as the only sign in ascending optic atrophy is not always useful. Fourthly, photography of the retinal nerve fiber layer showed that there is no correlation between the extension of the ischemic area and the sector angle of the defect of the retinal nerve fiber layer. Photography of the retinal nerve fiber layer can differentiative ischemic from non-ischemic retinal branch vein occlusion because of the qualitative detection of localized retinal nerve fiber layer defects. Consequently, this method is not only of great clinical importance for the diagnosis of different optic lesions, but is also useful for the prognosis and management of occlusion of the retinal branch vein. PMID- 1757035 TI - [Microcoagulation of the fundus. Experimental results of repeated laser pulse exposure]. AB - Angiographically visible lesions were produced in the fundus of rabbit eyes with repetitive 5 microseconds pulses and continuous wave exposures with 50-ms to 1-s pulse duration from an modified argon laser (514 nm). The ophthalmoscopic and the fluorescein angiographic findings showed less damage in the neural retina and the choroid after repetitively pulsed irradiation. Light microscopy and transmission electron microscopy showed that the neural retina and the choroid can mostly be spared by using repetitive 5 microseconds pulses, even though the damage to the retinal pigment epithelium is similar to the damage caused by continuous wave irradiation. Possible clinical applications, e.g. for macular edema and central serous retinopathy, are discussed. PMID- 1757036 TI - [Results of surgical therapy of advanced stages of retinopathy of prematurity]. AB - The results of buckling procedures performed in 15 consecutive cases of severe retinopathy of prematurity between 1983 and 1990 are presented and discussed. The preoperative status was stage IV in 6.7% und stage V with an open funnel in 93.3% of these cases. Anatomical success was found in 53.3% in the early postoperative phase, but this had fallen to 33.3% before the long-term follow-up examination. Functional success at least with perception of large forms was recorded in 20%. The surgical technique and postoperative complications are described. The results of closed vitrectomy performed in 104 consecutive cases of severe retinopathy of prematurity between 1983 and 1990 are then dealt with. The preoperative status was stage IV in 13.5%, stage V with an open funnel in 18.3% and stage V with a closed funnel in 68.2%. Anatomical success was achieved in 29.8% in the early postoperative phase, but the proportion fell to 13.5% during a long-term follow up study. Functional success at least with perception of hand movements was recorded in 10.6%. The surgical technique and postoperative complications are described. PMID- 1757037 TI - [Automated measurement of retinal vascular diameter]. AB - We describe a new unit of the Jena retinal camera for automatic measurement of retinal vessel diameter. The brightness profile perpendicular to the vessel is registered by CCD line sensor and the signal is transmitted to the computer. An adaptive computer program recognizes the edges of vessels and estimates the vessel diameters automatically. Applying several measurements per vessel, the intraindividual standard deviation may be smaller than 3%. By using the same objective measuring edge criterion, the measuring results are comparable between different observers and methods. Error sources are discussed. Measured vessel reactions to oxygen breathing and reduced perfusion pressure are presented to demonstrate the efficiency of this new method. PMID- 1757038 TI - [Effect of prednisolone on the course of optic neuritis. Results of a double blind study]. AB - The treatment of optic neuritis (ON) with corticosteroids has been controversial for many years. None of the previous studies with the usual dosage of steroids or ACTH has proven that this therapy is beneficial. However, these studies did not apply sensitive parameters for assessing the course of ON. The aim of this study was to examine the effect of corticosteroids using subtle parameters. The study design emphasized: 1. strict criteria for patient selection; 2. frequent controls during the initial period of the disease, follow-up for 1 year; 3. double-blind conditions with randomized groups; 4. assessment of the course with sensitive parameters, including visual acuity, visual evoked potentials (VEP) and the Tubingen Flikker Test, also called the Aulhorn Flicker Test, which monitors the activity of the ON. These last two tests were used for the first time in a controlled treatment study in ON. Thirty-eight patients with acute ON were treated orally in a double-blind procedure with either methylprednisolone (initially 100 mg daily, reduction every 3 days) or with vitamin B1 (100 mg thiamin daily) in the control group. The results of the Flicker Test and VEP showed a trend toward faster recovery under prednisolone within the first few weeks after onset of the disease. After 1 year none of the parameters examined showed any difference between the two groups. Thus, although prednisolone treatment in the dosage mentioned above seems to speed up recovery in the initial phase in some patients, no long-term benefit could be demonstrated. PMID- 1757039 TI - [Neuroretinal rim in eyes with simple optic atrophy]. AB - In comparison with normal eyes, eyes affected by glaucomatous optic nerve damage are characterized by a decreased neuroretinal rim area and an increased optic cup size. This study was performed to find whether eyes with nonglaucomatous optic nerve atrophy and normal eyes differ with respect to the neuroretinal rim. In all, 143 eyes with nonglaucomatous descending optic nerve atrophy and 563 normal eyes were biomorphometrically examined. The area and form of the neuroretinal rim and optic cup and the horizontal and vertical cup-to-disc ratios did not differ significantly between the two groups. These results are in part not supported by data in the literature. If they are confirmed by further studies, they will indicate that measurement of the neuroretinal rim and estimation of the cup-to disc ratios will not be useful for the diagnosis of damage to the descending nonglaucomatous optic nerve. It will be helpful for the differentiation of eyes with glaucomatous and nonglaucomatous optic nerve atrophy. PMID- 1757040 TI - [Mass screening of blue color vision in divers with the desaturated Lanthony-15 Hue Test]. AB - We tested 1002 persons, 572 divers (including 38 who had diving accidents) and 430 nondivers, for defects of the blue-sensitive system during the years 1988 and 1989. Recent research has shown functional disorders of color vision in divers, linked to previously described alterations of the retinal capillary system and pigment epithelium. The desaturated Lanthony-15-HUE test was used as a screening method. No defect of the blue-sensitive system was found, either in divers or in nondivers. Our results are similar to those of other researchers. One exception was that we found no correlation between age and error score. We found no evidence for retinal damage caused by diving. PMID- 1757041 TI - [Relevance of ocular pressure tonometry and classical tonometry with reference to prognosis in suspected glaucoma and ocular hypertension]. AB - A total of 44 eyes of patients with suspected glaucoma or ocular hypertension were examined both by ocular pressure tonometry (OPT) according to Ulrich and by tonography according to Leydhecker. The visual fields of these eyes were prospectively followed up for 3 years to compare the prognostic value of the two methods. In 30 of the 44 eyes a worsening visual field loss was observed, while in 14 the visual fields showed no change. Much better correlation was noted between values obtained by OPT and changes in visual field than between values obtained by tonography and visual field loss. Conventional tonography yielded 39% of false-negative values, but only 11% were recorded with OPT. Therefore, according to results of these and further investigations, OPT appears to be a more helpful and reliable method for assessment and decisions on therapy in patients with suspected glaucoma or ocular hypertension. PMID- 1757042 TI - [MK-507 (L-671 152): local tolerance and effectiveness of a new local carbonic anhydrase inhibitor in healthy probands]. AB - A three-dose, randomized, double-blind parallel, placebo-controlled ocular tolerancy study was undertaken in 24 healthy, normal volunteers with two formulations of 2% MK-507 (L-671 152), a novel water-soluble, topical carbonic anhydrase inhibitor. In this study MK-507 was administered to humans for the first time. Subjects received 3 sequential drops of the test drug in one randomly selected eye (at 13:00, 14:00, and 14:10 o'clock): ten received 2% MK-507 formulated with 0.5% hydroxyethylcellulose (HEC); ten, 2% MK-507 with no HEC; two, vehicle with HEC; and two, vehicle without HEC. Local tolerance of 2% MK-507 was good with predominantly mild and transient local symptoms, somewhat fewer for the formulation without HEC. Significant lowering of intraocular pressure (IOP) by up to 7 mmHg was noted when comparing IOP 4 h and 5 h after the first dose with IOP 20 h and 19 h before the first dose in the treated eyes of subjects receiving MK-507. Slightly greater activity was noted when MK-507 was formulated with HEC. PMID- 1757043 TI - [Modification of refraction and visual noise perception by suction cup oculocompression]. AB - In 17 ocularly healthy persons the IOP was artificially raised by suction cup oculopression (negative pressure: 65 mmHg [8.67 kPa]) from initially 15.5 +/- 2.2 mmHg (2.07 +/- 0.29 kPa) to 25.2 +/- 4.0 mm Hg (3.36 +/- 0.53 kPa) (mean +/- SD). Continuing the initial refractive correction, visual acuity (Landolt's rings) decreased from initially 1.06 +/- 0.13 to 0.39 +/- 0.22 (P less than 0.001* [*t test, paired ties each]). A new optical refraction with suction cup in position significantly raised the visual acuity to 0.64 +/- 0.24 (P less than 0.002*). The suction cup itself induced astigmatism of 2.15 +/- 1.46 dpt (Canon Auto Refractometer RK-1), which significantly differed from the initial astigmatism (0.32 +/- 0.23 dpt) (P less than 0.001*). The minus cylinder axis initially showed no preferential position. During artificial IOP elevation it shifted to 90 degrees...125 degrees (referred to the right eye) and thus ran about perpendicular to the meridian the suction cup was positioned on the eyeball. Effects of such refractive changes on differential light threshold and VEP amplitude are demonstrated. The results presented allow critical interpretation of previous IOP tolerance tests. The influence of suction cup oculopression on the perception of the white-noise field is shown in some glaucoma patients: the speed of the white-noise campimetry allows the increase in field defects during artificial IOP elevation to be followed up directly. PMID- 1757044 TI - [Diffuse and localized glaucomatous visual field changes in light sense, flicker and visual acuity perimetry. Evidence of pressure damage]. AB - 75 eyes of 75 patients with different types of glaucoma (21 eyes with normal tension glaucoma, 49 eyes with primary open-angle glaucoma and 5 eyes with pigmentary glaucoma) were examined by automated light-sense, flicker and resolution perimetry. All fields were classified as being "normal" (N) or having "diffuse loss" (D), "localized loss" (L) and "diffuse plus localized loss" (DL) in masked fashion. The frequency distributions for the various field loss categories against the highest intraocular pressure ever reported in the patients' records were plotted. The frequency distributions for the purely localized defects show a peak at 20 mmHg and are markedly skewed to low pressure values, while the diffuse plus localized damage and the purely diffuse loss, however, show a peak at about 30 mmHg. The data support the hypothesis that diffuse field loss may be an indicator of pressure-induced damage. PMID- 1757045 TI - [Sensitivity of noise field campimetry as a screening method for glaucoma]. AB - The glaucoma patient can perceive his or her visual field loss subjectively with snow field campimetry with the Tubingen electronic campimeter (TEC). The sensitivity of this new method of examination for glaucoma has not previously been evaluated. We were interested in finding whether absolute and relative scotomas could be detected with such high probability that snow field campimetry could be used as a screening method for the early detection of glaucoma. Analysis of the severity of scotoma is not possible, so that snow field perimetry can indeed by regarded as a screening procedure. A total of 76 eyes of 76 patients with glaucoma and stage I-IV visual field loss and 20 eyes of 20 patients with ocular hypertension were examined with threshold determining static perimetry (Octopus or Humphrey perimeter) and with the snow field of the TEC in controlled conditions. A qualitative comparison was drawn to evaluate how often a pathologic or normal finding was confirmed by snow field campimetry: of the 76 eyes affected by scotoma, 65 eyes (85.5%) showed pathologic findings consistent with the result of snow field campimetry, and 11 eyes showed normal findings. The visual field loss was 63.6% for glaucomatous visual field loss stage I: 90.9% for glaucomatous visual field loss stage II, and 95% for visual field loss stages III and IV. For 16 of the 20 eyes with ocular hypertensions normal findings were reported with snow field campimetry. Snow field campimetry is suitable for use as a quick screening procedure, but only for absolute glaucomatous scotomas. PMID- 1757046 TI - [Visually evoked cortical potentials for early detection of optic neuritis in ethambutol therapy]. AB - Ethambutol leads to chronic, severe optic neuritis with sudden onset in approximately 5-14% of all patients. Therefore, the ability of visually (pattern) evoked potentials for the early diagnosis of ethambutol-induced optic neuritis was tested. During ethambutol therapy prolonged latency was documented in 5 of 15 cases (33%). One of these 5 cases showed a reversible decrease in visual acuity. Thus, during treatment with ethambutol visually (pattern) evoked potentials may reveal a surprisingly high percentage of subclinical optic neuritis. These patients need close supervision in order to facilitate early discontinuation of the drug when neuritis develops. PMID- 1757047 TI - [Relation of visual acuity of test field luminance in glare sensitivity of various origin]. AB - Intolerance to bright light is a nonspecific ophthalmological symptom, originating either in disturbances of the optic apparatus of the eye or caused by functional disturbances of the neuronal network of the retina. Disturbances in brightness and darkness adaptation can often cause considerable decrease in visual acuity, which is not evident in the standardized tests that measure photophobia in conjunction with visual function. If the test field is very bright and the patient has photophobia, the visual acuity is often reduced considerably. The relationship between visual acuity and luminance of the test field was determined in glare--sensitive patients using a relatively simple method and a large range of luminances (0.1-30,000 cd/m2). In contrast to previously used methods, visual acuity was determined in a range where neuronal mechanism can be expected to be responsible for adaptation to brightness. We found disturbances in the relationship between visual acuity and luminance in several diseases, and it was especially pronounced in cone dystrophies. Affections of the optic nerve and opacities of the optic media usually did not cause a marked decrease in visual acuity at high luminances. As a supplemental investigation to mesoptometry and nyctometry, the method described here primarily permits types of photophobia to be determined that are not caused by stray light. The dynamic nature of neuronal adaptation processes determined by this test has therefore considerable influence on visual acuity. PMID- 1757048 TI - [Multisubstance analysis. Detection of changes in the optical density in individual layers of the optic fundus]. AB - A promising method for noninvasive objective diagnosis and monitoring of the course of a therapy is spectrometric investigation of the human ocular fundus. Application of this method in clinical practice depends on the development of suitable procedures for deconvolution of the measured spectra. The availability of microcomputers permits the performance of complicated calculations directly at the measuring device. Based on the two-photon flux theory, the influence of absorption and scattering in anatomically determined layers of the fundus will be considered. For this reason, an iterative principle for radiation transport into the fundus is introduced, allowing derivation of a physical model for calculation of the spectral course of the reflected light. In the multisubstance analysis a measured spectrum is approximated by the model function. During this analysis the optical densities of photosensitive and nonphotosensitive pigments and the reflection at intermediate layers can be calculated. As an example of multisubstance analysis, the deconvolution of foveal reflection spectra of normals and type I diabetics is demonstrated. This method makes it possible to show that early diabetic alternations occur in the choroid. PMID- 1757049 TI - [Changes in the pattern electroretinogram in glaucoma and ocular hypertension are dependent on stimulus frequency]. AB - A pattern electroretinogram (PERG) was recorded in patients in the initial stages of visual field defects resulting from open-angle glaucoma, in patients with ocular hypertension (OHT) and in age-matched controls. In both groups the visual acuity was above 0.8. Counterphasing checkerboard patterns were used as visual stimuli with a check size of 0.8 degrees and a range of reversal rates from 6 to 36 reversals/s. The most significant reductions of amplitudes due to glaucoma and OHT were observed at rates of 18 and 24 reversals/s (glaucoma: P less than 0.005 at 18 and 24 reversals/s, OHT: P less than 0.0005 at 18 reversals/s and P less than 0.0025 at 24 reversals/s). At reversal rates of 6 and 36 reversals/s the PERG was either not reduced (glaucoma and OHT: P greater than 0.01 at 36 reversals/s, OHT: P greater than 0.01 at 6 reversals/s) or reduced only marginally (glaucoma: P less than 0.01 at 6 reversals/s). When one takes the 95% confidence limits of normals into consideration, it is obvious that patients with glaucoma and patients with OHT have pathologic PERGs more often at 18 reversals/s than at other temporal frequencies. PMID- 1757050 TI - [Chronic lipogranuloma of the eyelids after paranasal sinus operations]. AB - Over a period of about 1 year we observed five patients who developed tumors of their eyelids a few days to 3 weeks after surgery on the paranasal sinuses through the nasal passage. One patient noticed a swelling of his ipsilateral eyelid during an irrigation procedure for the maxillary sinus, which was also followed by endonasal surgery. After surgery each patient developed an ipsilateral periorbital hematoma and subsequently solid indolent tumors of the eyelid without a tendency to regress over a period of 3 to 14 months. Therefore, surgical treatment was necessary. The histological examination showed lipogranulomas with giant cells and many lipid vacuoles of different size. Exploring the origin of these lipids, we performed a magnetic-resonance-spectrum analysis of one tumor sample. We predominantly found signals for linear hydrocarbons, which are the main components in paraffin-liquids. We presume that our patients developed lipogranulomas of their eyelids due to the paraffin introduced into the tissue by the ointment used to tampon the paranasal sinus after endonasal surgery. PMID- 1757051 TI - [Temporal tarsal strip-plasty for correction of malposition of the lower eyelid]. AB - The lateral tarsal strip procedure has the combined effect of increasing horizontal lid tension and adjusting the level of the lateral canthus. Following a lateral canthotomy a tarsal strip is created from the lateral aspect of the lower lid and sutured to the periosteum at the lateral orbital wall. Indications for this technique include senile and paralytic ectropion, recurrent entropion, congenital malpositions, and lid laxity following trauma or enucleation. The results yielded by this technique in 148 patients at the University Eye Hospital in Munich are presented. These included 53 suffering from paralytic ectropion in whom a medial canthoplasty was added to the lateral tarsal strip procedure. The two techniques combined provided symmetrical adjustment of the level of both lateral and medial canthal angles, a good position of the lacrimal puncta and increased lid tension. PMID- 1757052 TI - [Double-guided vacuum trephine system "Asmotom"]. AB - A new, doubly guided cornea suction trephine system is presented. By means of a suction rim placed on the limbus corneal and a suction disc in the centre of the cornea the vault of the cornea is preserved throughout the trephination procedure. Cutting is performed by a motor trephine, which rotates between the inner and the outer suction. The system allows creation of an absolutely safe perforation in a 360 degrees cut. The cut edges are precise and sharp. Both donor and recipient are trephined from the epithelial side. The endothelial cell loss is very low, amounting to 0.170 mm. The suction stabilization prevents any tilting of the trephine and avoids elliptical forms. Preliminary clinical experiences are presented. PMID- 1757053 TI - [Anesthesia effects on ocular circulation. Synopsis of a study]. AB - In a study of 280 patients (265 with cataract, 15 with strabismus), we investigated the ocular circulatory effects of 3 methods of anesthesia widely used in ophthalmic surgery, retrobulbar, peribulbar and general anesthesia. Retrobulbar anesthesia (RETRO) was performed with 2, 5 or 8 ml of a mixture (BLH Mix) of bupivacaine 0.75%, lidocaine 2% and hyaluronidase; with 5 ml BLH-Mix and addition of adrenaline in a low (1:500,000) or a higher (1:200,000) concentration; with 5 ml bupivacaine 0.75% or lidocaine 2% or mepivacaine 2%; with 5 ml mepivacaine 2% and addition of 150 units hyaluronidase; or with 5 ml BLH-Mix plus adrenaline and additional oculopression. Peribulbar anesthesia (PERI) was performed with 8 ml BLH-Mix (5 ml inferotemporally/3 ml superonasally) or 10 ml BLH-Mix (8/4) injected outside the muscle cone. General anesthesia was performed using halothane (inspiratory concentration 0.5 vol%) and nitrous oxide (65 vol%); respiration was adjusted to produce slight hyperventilation (alveolar pCO2 33 mmHg) or forced hyperventilation (pCO2 20-25 mmHg), respectively. The following variables were measured; systolic ciliary perfusion and blood pressures (PPs,cil and Ps,cil, respectively) and ocular pulsation volume (PVoc) using oculo oscillodynamography of Ulrich, and the intraocular pressure (IOD) using the Draeger handapplanation tonometer. RESULTS: (1) Measured 15 min after injection, PVoc was reduced by all local anesthesia (LA) methods by a range of 17-65%. The changes were dependent on the following factors: (a) increasing injection volume: larger PPs,cil reduction; (b) addition of adrenaline: larger reduction of all hemodynamic variables; (c) addition of hyaluronidase: more pronounced PVoc reduction; (d) type of local anesthetic: most marked PVoc reduction induced by RETRO with mepivacaine and bupivacaine, smallest reduction by lidocaine; (e) site of injection: less marked reduction of all hemodynamic variables during PERI than during RETRO with equal (8 ml) or equipotent (PERI 10, RETRO 5 ml) injection volumes; (f) additional oculopression: more marked Ps,cil reduction. The IOP, measured 15 min after injection, was increased by most LA types. The degree of IOP elevation was dependent on the following factors: (a) increasing injection volume: higher IOP elevation; (b) type of local anesthetic: lowest IOP elevation induced by bupivacaine, more marked effect of lidocaine, highest elevation after mepivacaine injection. After additional oculopressure, the IOP was reduced as expected. (2) During general anesthesia with slight hyperventilation, PPs,cil and Ps,cil were reduced by 20.6 and 27.6 mmHg, respectively, measured 15 min after intubation. PVoc was decreased by 50.8% and the IOP by 7.6 mmHg. With forced hyperventilation, the reduction of PVoc was even more pronounced. CONCLUSIONS: The anesthesia-induced lowering of both ocular perfusion and blood pressures as well as of the ocular pulsation volume, which is a measure of the pulsatile choroidal blood flow, can be interpreted as reflecting an inhibitory influence on ocular circulation. We suggest the following mechanisms to account for the changes during LA: elevation of IOP, adrenaline-induced retrobulbar vasoconstriction, LA-induced retrobulbar vasoconstriction (hypothetical), improved penetration of LA brought about by the orbital compression occurring during oculopression. The relative significance of the separate mechanisms differs, however, between the various LA types. The changes found during general anesthesia are attributable to the halothane-induced reduction of systemic blood pressure and cardiac stroke volume as well as to a relative hyperventilation induced choroidal vasoconstriction. The results are relevant for ophthalmic surgery with respect to the prevention of complications and problems depending on pathologic or at least unphysiological changes in ocular circulation, e.g... PMID- 1757054 TI - [Mydriasis caused by plant contact]. AB - Uni- or bilateral dilatation of pupils that are not reactive to light and lack miosis in response to 1% pilocarpine may be caused by contact with plants containing alkaloids such as scopolamine and atropine. Other causes of a non light-reactive dilated pupil, such as Adie's tonic pupil, third nerve palsy and lesion of the mesencephalic pretectal region, must be excluded before testing the iris sphincter reaction to 1% pilocarpine. Among the naturally growing flowers in Germany, deadly nightshade (Atropa belladonna), jimson weed (thornapple, Datura stramonium) and black henbane (Hyoscyamus niger) contain enough alkaloids to cause mydriasis by direct contact. However, in most cases an accidental mydriasis by plants in Germany is caused by Datura arborea taxa, e.g. Datura suaveolens, D. candida, D. aurea and D. sanguinea. They contain up to 0.6% dry weight scopolamine. These plants can grow very large and are often planted in tubs. They have to be cut back each year before the winter. This is typically how the eye is contaminated by parts of the plants, which can cause dilatation of the pupil mimicing a neuroophthalmological disorder. PMID- 1757055 TI - [Traveler's diarrhea--prevention, self care]. PMID- 1757056 TI - [Endoscopic ultrasound in gastroenterologic tumors]. AB - By means of endoscopic ultrasound (EUS) the visualization of the gastrointestinal wall Layers as well as a high-resolution imaging of the pancreas with neighbouring large vessels has become possible. EUS is especially sensitive in the local tumor staging in esophageal, gastric, pancreatic and ampullary carcinoma (accuracy rates 80-90%). Lymph node metastases are correctly identified in 70-80%. This also applies to the rectal cancer employing rigid instruments. Experience with colonic endosonography is still too limited to permit any definitive conclusions. For the primary diagnosis of submucosal tumors of the upper GI tract, and for the detection of small pancreatic lesions (e.g. endocrine tumors), endosonography is of high diagnostic accuracy. PMID- 1757058 TI - [A galenic diclofenac more wisely packaged?. Interview by Dr. T. U. Keil]. PMID- 1757057 TI - [Human geneticist from Wurzburg discovers a new hereditary disease. Schindler disease: an autosome recessive neuro-axonal dystrophy]. PMID- 1757059 TI - [Psychosis in organic brain syndrome. Melperon eliminates anxiety and restlessness]. PMID- 1757060 TI - Stress echocardiography: an overview. AB - Stress echocardiography has come a long way in the past ten to twelve years since it first began. There have been many procedural and technical advances. The results being obtained by those laboratories with active programs are very gratifying. Stress echocardiography is proving to be particularly valuable in women and in evaluating coronary angioplasty. Although the comparison between stress echocardiography and stress nuclear cardiology is actively being debated, the available data would suggest that the results are grossly comparable. There are certain subsets of patients which may be identified where one technique might excel over the other. The most important factor is undoubtedly the competence of the laboratory performing the test. A high quality nuclear study is clearly going to be better than a poor quality echocardiogram and vice versa. However, assuming a high degree of competence in either technique, stress echocardiography has many obvious practical advantages. There is no reperfusion necessary so that the patient does not have to return in four hours. There is no radiation involved. And the results are available immediately after the examination. For all of these reasons it is not surprising that stress echocardiography is gaining in popularity and should play an increasingly important role in the management of patients with coronary artery disease. PMID- 1757061 TI - [Stress echocardiography: a sensitive method in diagnosis of coronary heart disease]. AB - Prevalence of coronary artery disease requires sensitive diagnostic methods for screening and follow-up. The sensitivity of stress-ECG is low, 201-thallium scintigraphy is more sensitive but has the disadvantages of radiation and costs. Improved echocardiographic resolution with better identification of endocardial border as well as digital imaging technique have increased the interest in stress echocardiography as a diagnostic tool in coronary artery disease since a decade ago the clinical usefulness of stress echocardiography has been demonstrated. For stress echocardiography a semisupine bicycle position for continuous recording of echocardiographic images from the apical position in the two-chamber- and RAO view was developed. Echocardiographic images were digitized with a frame rate of 30/s and stored on optical discs with a storage capacity of 1 Gbyte. Rest and exercise images were analysed simultaneously for newly-occurring wall motion abnormalities or deterioration of already present hypokinesia or extension of existing wall motion abnormalities. Segmental wall motion was scored according to the scheme in Figure 2. In addition end-diastolic, end-systolic volume, and ejection fraction were calculated. In a patient population of 150, 30 female and 120 male, age 56.6 +/- 8.3 years, we could confirm the results reported by other working groups and demonstrate a high sensitivity in the diagnosis of single vessel disease. Our technique with the patient cycling in semi-supine position allows continuous echocardiographic registration during exercise and offers adequate image quality. The mean workload at peak stress was 127 +/- 30 watts, the maximal heart rate 137 +/- 18 bpm. Digital cine-loop imaging allowed evaluation of the examinations in about 90% of the cases. The sensitivity in the whole study group was 87%, the specificity 80%. Under full antianginal medication, 43% of the patients developed angina pectoris during exercise and 58% had a positive stress-ECG. The sensitivity in single-vessel coronary artery disease was 93% for the left anterior descending, 80% for the left circumflex, and 83% for the right coronary artery. These results in single-vessel disease were superior compared to findings of other authors using different techniques of stress echocardiography. In addition to the qualitative analysis, quantitative measurement of end-systolic volume and ejection fraction seems to be important. We found a significantly more pronounced decrease of ejection fraction at peak exercise in patients with multivessel disease compared to those with single vessel disease. In single-vessel disease ejection fraction was 61 +/- 12% at rest and 57 +/- 17% during exercise, this difference was not significant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1757062 TI - [Transesophageal echocardiography in combination with atrial stimulation for detection of ischemia-induced disorders of myocardial wall motion]. AB - The diagnostic value of exercise echocardiography has been widely reported. In up to 20% of patients conventional transthoracic exercise echocardiography however is impossible due to impaired image quality related to exercise. In addition some patients will not be able to perform a conventional bicycle exercise test due to joint disease or peripheral vascular disease or a sufficient stress is not possible because of lack of patient motivation. In an attempt to overcome these limitations, a system has been developed which combines transesophageal echocardiography with simultaneous transesophageal atrial pacing via the same probe. Three circular silver pacing electrodes were installed at a distance of 7,9 and 12 cm from the tip of the echoscope. Square wave pulses of 10 ms and an intensity of 7 to 20 mA were delivered. After baseline recording at the patient's spontaneous heart rate, atrial pacing was initiated at a rate of 100 beats/min and increased stepwise every 2 min by 20 beats/min up to 85% of the age-predicted maximal heart rate. Pacing endpoints were designated to be the development of angina pectoris or dyspnea, persisting horizontal or downsloping ST-segment depression (0.2 mV 80 ms after the J-point in the 12-lead ECG) or the development of new segmental wall motion abnormalities. In a group of 50 patients with suspected coronary artery disease, coronary artery disease (luminal narrowing of more than 70% of at least one major vessel) was detected with high sensitivity (greater than 93%) and specificity (greater than 100%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757063 TI - Dobutamine stress echocardiography: diagnostic utility. AB - Pharmacologic stress testing is an accepted alternative in those patients unable to perform exercise stress testing. The most prevalent form of pharmacologic stress testing remains thallium imaging during vasodilator stress with either dipyridamole or adenosine infusions. More recently, dobutamine stress echocardiography has emerged as a promising new technique for the evaluation of patients with known or suspected coronary disease. The rationale for the use of dobutamine infusion as a stress agent lies in its ability to simulate physical exercise through its beta-receptor agonist activity. This causes a supply-demand mismatch which in turn, creates regional myocardial dysfunction which can be detected by two-dimensional echocardiography. A major advantage in the use of echocardiography over other adjunctive imaging techniques is its ability to detect all forms of anatomic heart disease which may be associated with chest pain or may mimic ischemic chest pain. Our current dobutamine protocol involves stepwise infusion of dobutamine beginning at 5 micrograms/kg/min and increasing to 10, 20, and a peak of 30 micrograms/kg/min in three minute stages. Images are recorded in standard parasternal long axis and short axis, four chamber and two chamber views, digitized and displayed for comparison in a quad screen format. A 16 segment model is used for scoring wall motion abnormalities. Ischemia is considered present when a wall motion abnormality develops in an area with normal or only hypokinetic resting wall motion. The overall accuracy is between 85 and 90% for the detection of patients with coronary disease. In over 600 studies at our institution, no major side effects or complications have occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757064 TI - Dipyridamole-echocardiography in coronary artery disease. AB - Regional wall motion impairment incurred by means of dipyridamole-induced ischemia, is regarded with higher sensitivity and specificity than the conventional findings in the ECG. Based on the latter considerations, a new test, the dipyridamole echocardiogram has been introduced in which the development of regional wall motion impairment is designated as the positive diagnostic criterion. Dipyridamole is a vasodilator of coronary arterioles. During the course of the examination, three consecutively occurring mechanisms are considered responsible for the appearance of dipyridamole-induced ischemia in the presence of coronary stenosis. The ischemia is initially attributed to a steal effect, then to reflex-induced rise in rate-pressure product and, lastly, to a vasospastic component. In 680 patients with thoracic pain, on use of 0.84 mg/kg over ten minutes, there was a sensitivity of 74% in detection of angiographically documented coronary artery disease, defined as greater than 70% stenosis in at least one major coronary artery, and a specificity of 95%. The onset of regional wall motion impairment after dipyridamole infusion was correlated with the severity of the disease, the localization of the wall motion impairment enabled delineation of the localization of the stenosis in the coronary vascular system. By means of the dipyridamole echocardiogram, the effectiveness of therapeutic measures such as PTCA, ACVB, medical antianginal treatment and thrombolysis can be assessed. Lastly, the dipyridamole echocardiogram provides important information with regard to prognosis. PMID- 1757065 TI - Comparison of exercise echocardiography with myocardial perfusion scintigraphy for the diagnosis of coronary artery disease. AB - The rationale of exercise echocardiography for the diagnosis of coronary artery disease is based on the detection of exercise-induced wall motion abnormalities by ultrasound. Some of the problems that had previously limited the widespread application of the test have been solved by the development of digital recording and side by side cine loop display of two-dimensional echocardiograms: thus, respiratory artifacts can be eliminated, the examination is faster, and the comparison between rest and stress images has become practical and reliable improving sensitivity. The sensitivity and specificity of exercise echocardiography vary from 70 to 100%, according to patient selection, the protocol, and the gold standard used. Few studies studied the value of exercise echocardiography as compared to the more established nuclear cardiology imaging. Data from these comparative evaluations show a strong correlation between the two techniques for identifying and localizing myocardial ischemia. With good equipment and after proper training, exercise echocardiography can provide both diagnostic and prognostic information for routine clinical care. PMID- 1757066 TI - The histiocytoses of childhood. AB - The histiocytoses of childhood include Langerhans' cell histiocytosis, haemophagocytic syndrome (familial and reactive), sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), juvenile xanthogranuloma and malignant histiocytosis. These disorders show wide variation in their clinical presentation, prognosis and genetic implications. All are characterized by localized or generalized proliferation of histiocytes, but they differ in their morphology, histochemical and immunochemical staining patterns and electronmicroscopical features. On the basis of a comprehensive clinical history and critical interpretation of morphology and immunocytochemistry using an appropriately selected panel of antibodies, a diagnosis can be reached in the majority of cases. PMID- 1757067 TI - KP1 (CD 68) staining of malignant melanomas. AB - The monoclonal antibody KP1, which recognizes the CD 68 antigen on macrophages and myeloid precursors, was tested on 28 malignant (primary and metastatic) melanomas, 28 naevi, and 17 skin biopsies showing either normal (10) or hyperplastic melanocytes (7). Sixteen of 20 primary melanomas and six of eight metastatic melanomas showed variable numbers of KP1 positive tumour cells. All but five benign melanocytic proliferations (two Spitz naevi and three intradermal naevi), as well as normal and hyperplastic melanocytes were negative. These results indicate that difficulties may occur with the use of KP1 in the differential diagnosis between melanomas and neoplasms derived from histiocytes macrophages, and that the expression of CD 68 antigen might be related to tumour progression in melanocytic cells. PMID- 1757068 TI - Lichen planus pemphigoides: a clinicopathological study of nine cases. AB - Lichen planus pemphigoides is a rare condition characterized by blisters arising on normal or erythematous skin in a patient with concurrent lichen planus. It must be distinguished from bullous lichen planus, in which, as a consequence of severe basal cell hydropic degeneration, blisters arise within lichenoid papules or plaques. We present a clinicopathological study of nine cases of lichen planus pemphigoides, and report histological, immunofluorescent, ultrastructural and immuno-electronmicroscopical observations. We distinguish lichen planus pemphigoides from bullous lichen planus and consider the differential diagnosis. We propose that lichen planus pemphigoides does not represent a homogeneous condition: it may represent a number of bullous dermatoses that develop as a consequence of exposure of different basement membrane antigens following severe damage to the epidermal basement membrane as part of the lichenoid inflammatory process. PMID- 1757069 TI - Lethal arthrogryposis multiplex congenita: a pathological study of 21 cases. AB - Twenty-one cases of arthrogryposis multiplex congenita, which had resulted in death soon after birth or had been aborted following prenatal diagnosis, were studied. Histochemical and histological study of muscle indicated that 11 cases were of myogenic origin, including congenital muscular dystrophy in 10 cases from six families and nemaline rod myopathy in one. Neurogenic causation was established in five cases, including three with intra-uterine anoxic-ischaemic damage and two siblings with a severe form of cerebro-ocular-facio-skeletal syndrome. Causation remained uncertain in five. Unusual features included atrophy or amyoplasia of the diaphragm associated with lung hypoplasia in 10 cases and evidence of birth trauma in seven cases. One pair of siblings had subcutaneous tissue of doughy consistency and another pair had bladder hypertrophy. Familial recurrence was seen most often in cases with evidence of myogenic origin. We consider that neuropathology and muscle histochemistry are essential aids in determining the risks of recurrence in this group of lethal conditions which defy analysis by syndrome recognition techniques. PMID- 1757070 TI - Chromosomal translocation detected by bcl-1 and bcl-2 rearrangement in low-grade B-cell lymphomas in a European population. AB - Twenty-nine cases of non-Hodgkin's lymphoma of low-grade malignancy in a European population were investigated for the presence of bcl-2 and bcl-1 gene rearrangement. The cases were classified according to the Kiel classification. It was shown that bcl-2 gene rearrangements were exclusively confined to centroblastic-centrocytic lymphomas. bcl-1 rearrangements were found in two cases of chronic lymphocytic leukaemia. As the chromosomal translocation t(14;18) is reported to occur in up to 85% of follicular lymphomas, our results provide additional evidence that the differentiation of low-grade B-cell lymphomas according to the Kiel classification defines biologically distinct entities. PMID- 1757071 TI - Dystrophic amyloidosis: a local complication of tissue damage with heterogeneous distribution. AB - Seventeen consecutive patients with dystrophic amyloidosis are reported here (eight Chinese, three Indian, three Iban, two Malay and one Caucasian). Ten were females and seven males, with ages ranging from 12 to 80 years (mean of 48 years). Five instances of dystrophic amyloidosis occurred in areas of tissue damage in the cardiovascular system, including fibrotic cardiac valves and an atheromatous plaque. Three occurred in osteoarthritic joint tissue. Of note were three occurrences in endometriotic cyst walls, four in the fibrotic walls of epidermal cysts, one in a hernial sac and one at the edge of a skin ulcer. All deposits were congophilic and exhibited green-birefringence and permanganate resistance. Immunohistochemistry did not reveal reactivity for AA protein or immunoglobulin lambda or kappa light-chains. AP protein was detected in 35% of cases. Our results show that, besides the usual sites of osteoarthritic joints and damaged heart valves, dystrophic amyloidosis can complicate other areas of chronic tissue damage and fibrosis such as walls of cysts and ulcers. While the pathogenesis and biochemical nature remain unresolved, immunohistochemistry indicates that neither AA nor AL proteins are present in the deposits, and suggests that a different amyloid protein is involved. PMID- 1757072 TI - Primary squamous cell carcinoma of the endometrium. PMID- 1757073 TI - Ductal papilloma of the minor salivary gland. PMID- 1757074 TI - Lymphoepithelioma-like carcinoma of the uvula and soft palate: a rare lesion in an unusual site. PMID- 1757075 TI - Transitional mucosa of the colon associated with sigmoid volvulus. PMID- 1757076 TI - Identification of titanium pigment in drug addicts' tissues. PMID- 1757077 TI - Rheumatoid nodule in the breast. PMID- 1757078 TI - Immunolocalization of tumour necrosis factor alpha in lung tissue from patients dying with adult respiratory distress syndrome. AB - Using a mouse monoclonal antibody raised against recombinant human tumour necrosis factor alpha (TNF alpha), we have studied immunostained paraffin embedded autopsy lung tissues from 13 patients dying with adult respiratory distress syndrome and 10 control patients dying of unrelated conditions. Material from 12 of the 13 cases showed positive staining, strong in six, less strong in the remaining six. TNF alpha was located principally within epithelial cells resembling type II pneumocytes in both early and late stages of adult respiratory distress syndrome. In the early stages the TNF alpha positive cells were scattered and appeared disorganized, but in later cases they formed an epithelium. The cells were confirmed as epithelial by their staining pattern with monoclonal antibodies reactive with epithelial, cytokeratin and macrophage antigens, and by double staining for epithelial membrane antigen and TNF alpha. In the control group, staining for TNF alpha was confined to very occasional plump type II pneumocytes, and a weak reaction in bronchial lining cells. Macrophages were only weakly stained in either group. It is suggested that TNF alpha is synthesized (or possibly absorbed) by type II pneumocytes and may be involved in the production of, or recovery from, adult respiratory distress syndrome. PMID- 1757079 TI - Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. AB - Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy. PMID- 1757080 TI - The predictive value of histological classification into degrees of differentiation of squamous cell carcinoma of the larynx and hypopharynx compared with the survival of patients. AB - In the course of running two clinical trials between 1966 and 1985, data became available for 1315 patients, 713 in the first trial and 602 patients in the second trial, which has allowed comparison between histological findings in laryngeal and hypopharyngeal carcinoma, the observed survival and the tumour-free rates for these patients who were followed for up to 10 years. Extensive histopathology reviews have revealed over 98% agreement on tumour cell type between the initial report and that of the reviewer. Highly significant differences have been found for squamous cell carcinoma between the observed survival and the tumour-free rates for patients with well-differentiated and with anaplastic lesions. There was a statistically significant greater proportion of patients with well-differentiated tumours at larynx sites and in stage 1 when compared with patients with anaplastic tumours, but even when this was taken into account, multivariate analyses showed that tumour grading still made an independent significant contribution to the prediction of prognosis. For squamous cell carcinoma only very simple and rapidly assessed histopathological features need to be identified to classify tumours into the two grades employed in this study. The analyses have confirmed the prognostic significance of tumour grading in squamous cell carcinoma in the larynx and hypopharynx. PMID- 1757081 TI - Subungual malignant melanoma: clinicopathological features of 100 cases. AB - From the files of the Scottish Melanoma Group, we have identified 100 cases of subungual malignant melanoma (melanoma arising in the nailbed), and this represents 2.8% of the total melanomas registered during the period 1979-1989. Almost equal numbers arose on the foot as on the hand, with the thumb and big toe as the commonest digit affected. More than 80% were greater than 1.5 mm, with the mean Breslow depth 4.7 mm, and 70% were Clark level IV or V. Approximately half of the cases were of acral lentiginous type. At 5-year follow-up (54 cases), 26 have died of melanoma, six have died of an unrelated disease, four are alive with recurrence and 18 are alive and well. Features related to clinical outcome at 3 years were Breslow depth, mitotic count and the presence of vascular invasion. PMID- 1757082 TI - The histogenesis of inflammatory fibroid polyps of the gastrointestinal tract. AB - Inflammatory fibroid polyps are lesions occurring in the submucosa of the gastrointestinal tract. These lesions have been identified by a variety of names, indicative of their uncertain histogenesis. Three cases were studied by light microscopy and cytochemistry and, in one case, by electronmicroscopy. The most characteristic feature consisted of concentric fibrovascular structures. Peroxidase reaction for muscle actin and Ulex europeus agglutinin was positive in the two main cellular components. Electronmicroscopy revealed that the two principal cell constituents were endothelial and myocytic cells. These observations support the conclusion that inflammatory fibroid polyps are lesions of vascular origin. PMID- 1757083 TI - Effect of chewing Qat on mucosal histology and prevalence of Helicobacter pylori in the oesophagus, stomach and duodenum of Yemeni patients. AB - This investigation was aimed at assessing whether the Yemeni habit of chewing Qat on a regular basis had a significant effect on the upper alimentary tract. Seventy patients with dyspepsia attending Al-Thawra Hospital in Taiz, Yemen Republic were examined by endoscopy. Biopsies were taken from the oesophagus, stomach and duodenum. The patients included 28 who gave a history of daily Qat intake, 21 with less frequent intake and 21 who took none. The only statistically significant finding associated with daily Qat intake was a higher prevalence of duodenal ulcer, particularly in females. However, a strong association was also found between heavy smoking and ulcer, with most ulcer patients who chewed Qat daily being heavy smokers. Chewing Qat was not associated with a higher prevalence of oesophageal dysplasia, making it unlikely to be the cause of the perceived high incidence of oesophageal carcinoma in Yemen. There was a high prevalence of gastric H. pylori colonization (93%) and columnar-lined lower end of oesophagus (18%), as well as low prevalence of intestinal metaplasia of stomach (4%); this was not, however, related to chewing Qat. Further epidemiological and histological studies are needed to assess the significance of these findings in relation to the incidence of oesophageal and gastric carcinoma in Yemen. PMID- 1757084 TI - Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome? AB - Descriptions of the effect of androgens on ovarian human tissues are exceptional. This opportunity was provided for us by 17 women with transsexualism--female to male transsexuals (TSX)--who had been given androgens for a mean period of 21 months before hystero-salpingo-oophorectomy took place. Twenty-nine ovaries from TSX and 14 control ovaries from 13 regularly cycling women were examined. As compared with controls, TSX ovaries were enlarged and displayed a two-fold increase in cystic follicles and a 3.5-fold increase in atretic follicles; the ovarian cortex was collagenized and three-times thicker. Theca interna hyperplasia and luteinization were uniformly observed in TSX cystic follicles. Stromal hyperplasia was a constant finding in TSX ovaries, accompanied by clusters of luteinized stromal cells in 12 cases. Eventually, these findings met the histological criteria for the diagnosis of polycystic ovaries. These observations demonstrate that androgens alone may induce polycystic changes. The assumption that the role of androgens is pivotal at the follicular level- inducing follicle growth arrest and accelerating cystic changes--in the genesis of polycystic ovaries is reinforced. PMID- 1757085 TI - AgNOR counts in recurrent and non-recurrent meningiomas. PMID- 1757086 TI - The testicular 'tumour' of adrenogenital syndrome--a persistent diagnostic pitfall. PMID- 1757087 TI - Cellular blue naevus associated with osteoma cutis. PMID- 1757088 TI - Peripheral T-cell lymphomas. PMID- 1757089 TI - APTES, a section adhesive for immunocytochemistry; and experiences of slide drying at room temperature. PMID- 1757090 TI - Analysis of X-chromosome inactivation in X-linked immunodeficiency with hyper-IgM (HIGM1): evidence for involvement of different hematopoietic cell lineages. AB - The pattern of X-chromosome inactivation was analyzed, by means of two different DNA probes (pSPT-PGK and M27 beta), in several cell lineages derived from females belonging to a pedigree with X-linked immunodeficiency with hyper-IgM (HIGM1). Non-random X-chromosome inactivation was demonstrated in T cells, B cells, and neutrophils, but not in fibroblasts, of obligate carriers, suggesting that different hematopoietic cell lineages are primarily involved in HIGM1. Preferential inactivation of the paternally derived X-chromosome was demonstrated by analysis of segregation of the alleles defined by the pSPT-PGK and M27 beta probes. The possibility that the HIGM1 mutation may confer a proliferative and/or differential advantage to hematopoietic precursors carrying the mutated allele on the active X-chromosome is discussed. PMID- 1757091 TI - Normal variants of human mitochondrial DNA and translation products: the building of a reference data base. AB - A good standard reference for the highly polymorphic human mitochondrial DNA (mtDNA) sequence is essential for studies of normal and disease-related nucleotide variants in the mitochondrial genome. A consensus sequence for the human mitochondrial genome has been derived from thirteen unrelated mtDNA sequences. We report 128 nucleotide variants of the human mtDNA sequence, and 62 amino acid variants of the human mitochondrial translation products, observed in the coding region of these mtDNA sequences. PMID- 1757092 TI - Fine mapping of a human chromosome 6 ferritin heavy chain pseudogene: relevance to haemochromatosis. AB - We have used a somatic cell hybrid regional mapping panel for the short arm of chromosome 6, linkage analysis and a population study to map in detail a previously described ferritin heavy chain pseudogene sequence on chromosome 6. Our results show that this sequence maps to the short arm of chromosome 6 centromeric to the glyoxylase locus. The ferritin pseudogene locus is thus distant from the locus for the iron storage disease haemochromatosis, confirming previous evidence that this sequence is not a candidate for the haemochromatosis gene. PMID- 1757093 TI - Recurrence of a nonsense mutation in the NF1 gene causing classical neurofibromatosis type 1. AB - The gene responsible for von Recklinghausen neurofibromatosis (NF1) has recently been identified, and several point mutations and deletions have been described. The availability of intron-exon boundaries of several exons of the NF1 gene facilitates the search for mutations in affected patients. We have analysed 38 patients for mutations in exon 4 of the NF1 gene, and found one patient with a C- --T transition at base position 1087 of the cDNA, changing an arginine codon to a stop codon, at amino acid position 365. Sequencing of other members of the family, including both parents, did not show the mutation, confirming that this mutation is responsible for this sporadic NF1 case. As the mutation described here was previously identified in an independent case by others, this case represents a recurrence of this mutation and suggests that codon 365 might be a hot spot for mutations in the NF1 gene. Thus, a specific search for this mutation should be performed when studying NF1 sporadic or familiar cases for genetic analysis. PMID- 1757094 TI - Identification of a mutation in the promoter region of the dystrophin gene in a patient with atypical Becker muscular dystrophy. AB - We have identified 7 patients with Becker muscular dystrophy (BMD) in whom analysis of dystrophin by immunoblotting shows a full-sized molecule produced at reduced abundance compared with controls. They have no detectable deletion in their dystrophin cDNA. One patient presented atypically with unusually severe cramps as his only symptom for 25 years. These patients were investigated using the polymerase chain reaction (PCR) with 3 sets of primers within the promoter region of the dystrophin gene, followed by dot blot and restriction analysis. In the patient with the atypical history, one of the expected fragments on PCR failed to amplify. A large deletion was excluded by the finding of normally sized fragments on amplification with the other primer sets. The mutation was localised to the 3' end of the forward primer binding site by dot blot and restriction analysis. This result supports the hypothesis that, in patients with a full-sized dystrophin molecule produced at reduced abundance, the phenotype may result from a mutation in the promoter region of the dystrophin gene. The atypical history of the patient in whom this was detected adds to the variety of phenotypes now known to exist as BMD. PMID- 1757095 TI - Low density lipoprotein receptor founder mutations in Afrikaner familial hypercholesterolaemic patients: a comparison of two geographical areas. AB - Afrikaners with familial hypercholesterolaemia (FH) were screened for the presence of three point mutations in the low density lipoprotein receptor gene that were previously described as being relatively common in this population. The prevalence and distribution of the mutations were compared in 27 unrelated homozygous and 79 unrelated heterozygous FH Afrikaner patients from two regions in South Africa, the Transvaal and Cape Provinces. The relative distribution of the three mutations was similar in the two regions, with the FH1 mutation being the most prevalent (66%), followed by the FH2 mutation (27%) and the FH3 mutation (7%). Interestingly, defects other than the three common mutations are more common in the Cape than in the Transvaal; thus the three known mutations account for 98% of FH alleles in the Transvaal and only 74% in the Cape Province. None of the patients carried the recently described familial defective apolipoprotein B100 mutation. These results establish that three "founder" mutant genes occur amongst the Afrikaner and are responsible for the overall high prevalence of FH in this population. PMID- 1757096 TI - Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus. AB - Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops. PMID- 1757097 TI - Identification of common variant alleles of the human guanosine monophosphate reductase gene. AB - Examination of nucleotide sequences of genomic DNA samples obtained from several unrelated Caucasians and orientals revealed the existence of four variant alleles in the chromosome 6-linked quanosine monophosphate reductase locus. The wild-type gene has T at position 42 (counting from A of the chain initiation codon), C at 630, G at 700, and T at 766, i.e., its structure is T(42)-C(630)-G(700)-T(766). The variant gene, T-T-G-T, was found in about 10% of the loci examined. The C-to T change at 630 was silent and did not induce any amino acid substitution (His at amino acid residue 210), but it created an additional NcoI cleavage site in the variant gene. The frequency of another variant, the T-C-G-A gene, was about 30%. The T-to-A change at 766 caused an amino acid substitution Phe----Ile at amino acid residue 256 in the variant protein. Frequencies of the C-C-G-T variant and the T-C-A-T variant were probably lower than 5% in Caucasians and orientals. PMID- 1757098 TI - Oto-palato-digital syndrome type I: further evidence for assignment of the locus to Xq28. AB - The oto-palato-digital syndrome (OPD) is a rare X-linked disease with diagnostic skeletal features, conduction deafness, cleft palate and mild mental retardation. Differences in clinical presentation between families have led investigators to classify OPD into two subtypes: type I and type II. A linkage study performed in one family segregating for OPD I has recently suggested linkage to three marker loci: DXS15, DXS52 at Xq28, and DXS86 at Xq26. We have investigated an additional OPD I family for linkage by using distal chromosome Xq DNA probes. The linkage data and the analysis of recombination events that have occurred in this family excluded, definitively, the Xq26 region for OPD I, and provide further support for mapping the mutant gene close to the cluster of tightly linked markers DXS15, DXS52 and DXS305 at Xq28. PMID- 1757099 TI - Xeroderma pigmentosum complementation group H is withdrawn and reassigned to group D. PMID- 1757100 TI - Toxins, cytokines, immunity and pathology. PMID- 1757101 TI - The heat shock response in human phagocytes. AB - During the last 10 years the intriguing field of the heat-shock response and stress proteins has switched from a particular case to a phenomenon of general interest. Discovered in Drosophila, these proteins were observed in every living organism with a surprisingly high sequence homology. In addition, these proteins are not only inducible by stress or pathophysiological situations but are also expressed in unstressed cells. These are arguments for crucial roles of heat shock proteins. Here we discuss some aspects of the heat shock/stress response that we observed in phagocytic cells after phagocytosis with regard to their physiologic functions such as oxygen-free radical generation, antigen processing and presentation. PMID- 1757102 TI - The CNS acute inflammatory response to excitotoxic neuronal cell death. AB - Acute inflammation is a stereotyped non-specific response to tissue injury which results in the recruitment of neutrophils and monocytes within minutes. In this study the myelomonocytic and microglial reaction to neuronal destruction following unilateral hippocampal injection of kainic acid neurotoxin was investigated. Despite extensive acute neuronal necrosis and notwithstanding a leaky blood-brain-barrier, there is no neutrophil recruitment and a 2-day delay before any increase in macrophage-microglial cell numbers. Resident microglia are capable of reversible upregulation to an activated morphology and the macrophage microglial reaction is seen not only at the injection site, but also at distant sites related to the axonal pathways and synaptic terminals of the killed neurons. PMID- 1757103 TI - Imbalanced cytokine production by macrophages from autoimmune-prone mice. AB - Peritoneal macrophages from multiple autoimmune-prone strains of mice (MRL/lpr, MRL/+, NZB/W, BXSB, and B6/gld) show defective expression of the cytokines IL-1 and IL-6. Autoimmune mice were all used between 1 and 6 weeks of age, the earliest times being well before the onset of overt disease. Northern blot analysis reveals a parallel reduction in the levels of IL-1 alpha, IL-1 beta, and IL-6 mRNA. In contrast, the production of other proteins, including the cytokine TNF-alpha, appears to be normal. These findings imply an imbalance within the cytokine network of autoimmune macrophages. Studies on bone marrow-derived macrophage precursors, as well as macrophages from chimeric mice, suggest an intrinsic macrophage defect as opposed to conditioning by the autoimmune environment. This defect appears to be constant throughout the lifespan of autoimmune MRL/lpr mice, being equally apparent in 1-week old mice as in fully diseased 6-12-month-old mice. Aberrant regulation of IL-1 and IL-6 represents a novel defect in the function of autoimmune macrophages that is both intrinsic and substantial, and has the potential to contribute to the immune dysregulation that characterizes autoimmunity. PMID- 1757104 TI - Role of cytokines in killing of intracellular pathogens. PMID- 1757105 TI - The role of rIL-2 in the modulation of cellular immunity in resistance to infection. PMID- 1757106 TI - Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and elastase, inhibit the function of the cells of the immune system (phagocytes, NK cells, T cells), inactivate several cytokines (IL-1, IL-2, IFN-r, TNF), cleave immunoglobulins and inactivate complement. Inhibition of the local immune response by bacterial proteases provides an environment for the colonization and establishment of chronic infection. The other mechanism by which P. aeruginosa evades the host defence system is the biofilm mode of growth of the bacteria in chronic infections. The biofilm-grown bacteria induce a low phagocyte response, and provide a barrier for the bacteria against antibodies, complement, and the cells of the immune system. Protection from the host defence system combined with increased antibiotic resistance of the bacteria in the biofilm are the major reasons for the persistence of P. aeruginosa in chronic infections. PMID- 1757107 TI - Inhibition of human immunodeficiency virus infection in monocytes by monoclonal antibodies against leukocyte adhesion molecules. AB - CD4 is the surface receptor for HIV envelope. Some evidence exists, however, that other cell surface receptors may be involved in viral entry subsequent to the initial binding of gp120 to CD4. Antibodies to leukocyte integrin LFA-1, a major component of intercellular adhesive interactions, have been shown to inhibit HIV induced syncytia formation. Using a stringent system for in vitro HIV infection of human leukocytes, we examine the ability of some monoclonal antibodies (mAb) against various adhesion-related molecules to block or partially inhibit productive viral replication. HIV-1 infection of target monocytes or T cells by cell-free virus was blocked completely or partially by some mAb that prevent cell cell interactions (CD4, HLA-DR, LFA-1, LFA-3), but not by others (ICAM-1, MAC-1, gp150.95, CD2, CD3, CD14). The capacity for mAb to block HIV infection appears to be epitope-specific, and does not relate to the ability to block homotypic adhesion. HIV transmission from infected cells was more difficult to block than was infection by cell-free virus. Adhesion molecules may be involved in facilitating early stages of HIV infection, following gp120/CD4 binding but prior to viral integration, in a manner distinct from cell-cell adhesion. PMID- 1757108 TI - In vivo efficacy of virus-derived peptides and virus-specific cytotoxic T lymphocytes. AB - The in vivo efficacy of virus- and tumor-specific cytotoxic T lymphocytes (CTL) is discussed as well as ways to activate these cells in vivo with lymphokines, monoclonal antibodies and immunization. In vivo and in vitro peptide immunization can induce such virus- and tumor-specific CTL but several questions have to be answered before peptide vaccination can be implemented as a novel immunotherapeutic or preventive approach in man. PMID- 1757109 TI - Protection by alpha-thalassaemia against Plasmodium falciparum malaria: modified surface antigen expression rather than impaired growth or cytoadherence. AB - We have attempted to determine the cellular mechanism by which alpha-thalassaemia may protect against Plasmodium falciparum malaria. Invasion and development of P. falciparum in the microcytic red cells of two-gene deletion forms of alpha thalassaemia when measured morphologically or by [3H]hypoxanthine incorporation were normal compared to controls. Normal invasion rates were also observed following schizogony in thalassaemic red cells. Neither the addition of the oxidant menadione, 30% oxygen, nor modified medium, produced differential damage to parasites within thalassaemic cells. Furthermore, there were no significant differences in the binding of P. falciparum-parasitized alpha-thalassaemic and normal cells to C32 melanoma cells in vitro. However, when neoantigen expression on the surface of infected thalassaemic cells was estimated using a quantitative radiometric antiglobulin assay, clear differences were observed. It was found that alpha-thalassaemic cells bound higher levels of antibody from serum obtained from individuals living in a malaria endemic area than control normal red cells. The binding ratio for thalassaemic compared with controls was 1.69 on a cell-for cell basis, and 1.97 when related to surface area. The binding of antibody from immune serum increased exponentially during parasite maturation. We also found increased binding of naturally occurring antibody present in non-immune serum to parasitized thalassaemic red cells which also increased during parasite maturation. We conclude that the protection afforded by thalassaemia against malaria may not reside in the ability of parasites to enter, grow or cytoadhere to endothelium in such cells, but may be related to immune recognition and subsequent clearance of parasitized red cells. PMID- 1757110 TI - Genetic regulation of macrophage priming/activation: the Lsh gene story. AB - This paper describes functional and genetic studies on the macrophage resistance gene Lsh/Ity/Bcg first described almost two decades ago. Working in vitro with resident peritoneal, liver (Kupffer cells) and bone marrow derived macrophages from congenic B10 (LshS) and B10.L-LshR mice it has been possible to demonstrate that the final effector mechanism for the gene in regulating antileishmanial activity involves production of reactive nitrogen rather than reactive oxygen intermediates. This in turn is dependent upon priming/activation of macrophages for enhanced TNF-alpha release which acts back on the macrophage in an autocrine manner to increase nitric oxide production. The precise point at which Lsh acts to control macrophage priming/activation has not been identified, but studies of early response gene expression show differences in KC mRNA levels at 2 h after LPS stimulation, and in c-fos mRNA as early as 20 min after stimulation with PMA plus ionophore, in peritoneal macrophages from congenic LshS and LshR mice. Data available suggest that both negative and positive signals may be involved in macrophage priming/activation, with LshS macrophages down-regulating their capacity for continued response to the autocrine loop. Work in progress will examine the role of TPA and cAMP response element-binding proteins in regulating gene expression in Lsh congenic mice. A major new initiative has also commenced to clone the Lsh gene by reverse genetics using yeast artificial chromosomes to walk towards Lsh from the closet proximal and distal markers on mouse chromosome 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757111 TI - Immune responses to filarial parasites. AB - Filarial nematode parasites are long-lived organisms which are responsible for one of the major tropical diseases. Their ability to survive may be related to the antigen-specific anergic state observed in carriers of the parasite. Severe disease symptoms are associated with the breakdown of anergy. Different stages of the parasite life cycle are anti-genetically distinct, and a state of concomitant immunity is therefore possible which prevents superinfection. The evidence for these conclusions is discussed, in the context of the need for an effective vaccine against filarial parasites which will avoid any risk of increasing disease severity. PMID- 1757112 TI - Enhancement of MHC class II antigen expression by exposure to Candida albicans. AB - In oral infections with the yeast Candida albicans, the expression of MHC class II antigens on keratinocytes has been reported to be enhanced. In the present experiments, exposure to C. albicans or its products in vitro was found to increase the expression of class II MHC antigens on thioglycollate-induced mouse macrophages, and on LK cells (an antigen-presenting cell line). The implications of this finding for the understanding of immunoregulation and susceptibility to C. albicans infection are discussed. PMID- 1757113 TI - Control of parasitic diseases: a complementary role for vaccines and drugs. AB - This paper seeks to substantiate its title by discussion of three key questions: why are we attempting to develop parasite vaccines? Will we be successful? If we are, will there still be a need for chemotherapy? It concludes that: parasite vaccines are likely to be safer, cheaper and more efficacious as prophylactics than antiparasite drugs; in time vaccines will be developed for some but not all human parasitic diseases; at least in the short and medium term, drugs will be needed for those already infected and for those for whom, for whatever reason, a vaccination strategy fails. PMID- 1757114 TI - Pneumococcal conjugate vaccines. AB - We have prepared conjugates of pneumococcal type 4 polysaccharides (PS4) or oligosaccharides to tetanus toxoid using the carbodiimide method. The use of a spacer, 6-aminohexanoic acid, resulted in higher incorporation of carrier protein. Conjugates contained up to 10% free polysaccharide, but no free protein. In general, polysaccharide conjugates induced higher anti-PS4 IgG antibody titers than oligosaccharide conjugates. Conjugates with the highest amount of incorporated protein were the most immunogenic. The response to conjugated PS4 does show characteristics of a T cell-dependent antibody response, in terms of both isotype distribution and induction of immunological memory. Repeated immunization with high doses of PS4TT conjugate resulted in a virtually negative anti-PS4 IgG response, suggestive of the induction of high dose tolerance. PMID- 1757115 TI - In vivo effects of TRH, T3 and cGH on antibody production and T- and B lymphocytes proliferation in immature male chickens. AB - Newly hatched White Leghorn male chicks were used in this study. Different doses of T3 (0.1 or 1 ppm) or TRH (1 or 5 ppm) were administered in the feed for an 8 week period. Chicken growth hormone (cGH) (10 micrograms/kg BW) was injected (i.v.) into a different group of chicks twice daily for 1 week starting at 7 weeks of age. A different group received both T3 (0.1 and 1 ppm) and cGH. Serum concentrations of T4, T3 and GH, antibody production against sheep red blood cells (SRBC) and Brucella Abortus (BA), and in vitro proliferative response of both T- and B-lymphocytes to mitogenic stimulation were measured. Supplementation of T3 (1 ppm) significantly lowered T4 and increased T3 concentrations. No effect of any hormone treatment on antibody production was observed. T3 supplementation and cGH injection alone or with T3 (0.1 ppm) significantly increased blastogenic response of lymphocytes to either Con-A or LPS mitogenic stimulation. It was concluded that T3 and GH are involved in lymphocyte activity of chickens. PMID- 1757116 TI - Isolation and characterization of anti-H antibody from egg yolk or immunized hens. AB - An anti-H antibody was demonstrated to be produced in egg yolk as well as in serum of hens which were immunized with human type O red blood cells. The antibody in egg yolk was isolated with polyethylene glycol and ethanol and was purified by affinity chromatography using immunoadsorbant beads immobilized with H type 2 hapten (Fuca1----2Gal beta 1----4GlcNAc beta). Hemagglutination reaction of the antibody from egg yolk was inhibited by human saliva samples from secretor types irrespective of their ABO blood types, and by immunoadsorbant beads which contain Fuca1----2Gal beta structures. PMID- 1757117 TI - Standardization of ELISA for the detection of anti-cardiolipin antibodies--effect of non-specific IgG binding. AB - Various frequencies of anti-cardiolipin antibodies reported in patients with systemic lupus erythematosus and other autoimmune and infectious diseases necessitates the need for standardization of the immunoassay. We report here the usefulness of "no-antigen" control for each serum in determining the actual value of the anti-phospholipid antibodies. This non-specific "no-antigen" binding was quite variable from serum to serum and in general was higher in the patient population than in healthy individuals which served as controls. This non specific binding may be associated with the increased IgG content of the sera as shown by the linear association of the absorbance of the back-ground readings to increases in IgG concentration (correlation coefficient 0.98). PMID- 1757118 TI - Modulation of T and B cell proliferative responses by factors present in rat salivary glands. AB - Rat salivary gland culture supernatants (SGSN) were shown to inhibit the proliferation of rat spleen cells induced by the mitogens concanavalin A (ConA), phytohaemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS) and S. typhimurium mitogen (STM). The responses of B cells were more markedly inhibited than the responses of T cells. Factors contained in SGSN which had a molecular weight smaller than 3500 inhibited all responses, whereas factors greater than 3500 only inhibited responses induced by PWM, LPS or STM. Factors present in SGSN also inhibited the proliferation of two B cell hybridoma cell lines, as well as the IL-2-responsive cell line CTLL-2 and the IL-4-responsive cell line CT.4S. However, SGSN factors having a molecular weight greater than 3500 did not inhibit CTLL-2 proliferation. These data indicate that rat salivary glands contain factors which differentially regulate T and B cell proliferative responses in vitro and which may modulate localized immune responses in the salivary gland in vivo. PMID- 1757119 TI - IL4, IL5 and IL6-mediated regulation of immunoglobulin (Ig) heavy chain class switching and Ig production by gut-associated lymphoid tissue (GALT) B cells from athymic nude (nu/nu) mice. AB - Gut mucosal immunoglobulin (Ig) isotype expression and secretion are known to be regulated by B cell-stimulatory factors (BSF), lymphokines or cytokines from T and non-B cells. The class and amount of Ig secreted appear to depend on the presence of a combination of these factors. The effects of IL-4 and IL-5 on Ig class switching by gut mucosal B cells remain controversial. To shed further light on this issue, young (1-2 months old) athymic nu/nu murine GALT B cells were chosen, because the possibility of in vivo effects of T cells on B cells (in particular at the levels of transcription and translation without changes in surface Ig phenotype expression) cannot be excluded. The results are summarized below. IL-4, IL-5 and IL-6 alone or in combination do not act as IgA heavy chain switch cofactors, but IL-5 and IL-6 do act at least as B cell terminal differentiation factors for any isotype-specific gut-associated lymphoid tissue (GALT) (mesenteric lymph node) B cells in the presence or absence of LPS. The BSF have augmenting effects on class-specific Ig production by GALT sIgM-bearing B cells, when these are treated with the BSF alone. IL-4 alone or in combination with other BSF prevents LPS-stimulated IgM production. BSF without LPS do not evoke production of significant amounts of IgG and IgA by high density (HD) and low density (LD) sIgM-bearing B cells; IgM is synthesized only in small amounts of LD sIgM-bearing B cells in the presence of IL-5 and/or IL-6. There is no difference in the responsiveness of GALT and spleen sIgM-bearing B cells to the BSF. PMID- 1757120 TI - An improved PVC strip ML-ELISA technique for diagnosis of recent cases of amoebiasis. AB - Conventional plate ML-ELISA technique for diagnosis of recent cases of amoebiasis was converted into a simple polyvinyl chloride strip multilayer-enzyme linked immunosorbent assay (PVC strip ML-ELISA). This report details the development and preliminary characterization of the PVC strip ML-ELISA method for Entamoeba histolytica antigen detection in human fecal samples. In addition, we evaluated the relative efficacies of the PVC strip ML-ELISA and the conventional plate ML ELISA methods by screening different categories of amoebiasis patients and other intestinal parasites. A significant correlation was found (P less than 0.01) between the two assay methods with reference to sensitivity and specificity of detecting E. histolytica antigens. However, with reference to operational case and economy, the PVC strip ML-ELISA may be performed even by paramedical technical personnel under field conditions. PMID- 1757121 TI - Lymphocyte blastogenic responses in sickle cell disease. AB - Cell mediated immunity (CMI) has not been extensively studied in sickle cell disease (SCD). In this study, an assessment of lymphocyte blastogenic responses was done in 62 SCD patients (62 steady state and 25 in crisis with or without documented infection), along with 30 normal controls in good health and 10 with various infections. The mitogen phytohemagglutinin (PHA) and two antigens (Candida albicans and Tetanus Toxoid) were used as stimuli. An evaluation of these results by stimulation index revealed 53/62 (86%) of SCD steady state patients, 30/30 (100%) of healthy controls and 7/10 (70%) of normal control patients with infection positively responded to all three stimuli. Conversely, only 5/25 (20%) of SCD crisis state patients had totally normal blastogenic responses. Analysis of the data from SCD crisis patients revealed 14/20 (70%) with abnormally depressed proliferation to PHA, 11/20 (55%) to Candida and 6/20 (30%) to Tetanus. When comparisons were made by mean counts per minute, the most striking finding was the PHA response in the SCD crisis state. In this group the mean counts per minute were significantly less than the three other groups by statistical analysis. This data suggests that the crisis state, especially when associated with infection, profoundly effects blastogenic responses to PHA and to a lesser degree in vitro antigenic stimulation. The normal group with infection showed similar diminished blastogenesis to antigen, but no effect on mitogen response. PMID- 1757122 TI - PAF induces rat plasma extravasation and releases eicosanoids during anaphylaxis. AB - The effects of anaphylaxis on vascular protein extravasation in selected tissues and on the release of prostaglandins in the peritoneal cavity were studied in sensitized rats. Extravasation of Evans blue dye was used as a measure of vascular permeability. Specific antigen challenge increased by 279, 297, 328, 250, and 192% the protein extravasation in the trachea, upper and lower bronchi, pancreas, and duodenum, respectively, but did not modify significantly the vascular permeability of the lung parenchyma, heart, liver, and kidney. Extravasation of Evans blue dye also was increased by 43-fold in the peritoneal cavity. Pretreatment of the animals with indomethacin (10 mg/kg) did not modify significantly the protein extravasation of the trachea, upper and lower bronchi, pancreas, and duodenum induced by anaphylaxis. Pretreatment with a mixture of mepyramine (3 mg/kg) and methysergide (2.5 mg/kg) reduced by 62, 66, and 40% the protein extravasation in the trachea, upper bronchi, and peritoneal cavity, respectively, in similar conditions. The PAF antagonist BN-52021 (5 mg/kg) very strongly reduced the protein extravasation elicited by anaphylaxis in the trachea, upper and lower bronchi, pancreas, and duodenum by 72, 87, 82, 67, and 85%, respectively, and by 53% in the peritoneal cavity. Anaphylaxis also increased the concentrations of thromboxane B2 and leukotriene B4 in the peritoneal exudates, but prostaglandin E2 levels were not affected. Pretreatment with BN-52021 reduced by 29 and 75% the level of thromboxane B2 and leukotriene B4 in the exudates. These results suggest that PAF, histamine, and serotonin mediate the protein extravasation associated with anaphylaxis, whereas prostaglandins are likely to play a minor role in this reaction. PMID- 1757123 TI - Circulating phospholipase A2 activity associated with sepsis and septic shock is indistinguishable from that associated with rheumatoid arthritis. AB - Elevation of circulating phospholipase A2 (PLA2) activity is associated with sepsis and septic shock. Elevated levels of PLA2 activity also are seen in association with chronic inflammatory disorders such as rheumatoid arthritis. The relationship between these phospholipases is unclear. We have developed a highly specific enzyme-linked immunosorbent assay (ELISA) capable of measuring human synovial PLA2 in plasma, using monoclonal antibodies raised to recombinant synovial PLA2. This ELISA has been used to quantitate circulating PLA2 levels in patients clinically diagnosed with sepsis. These elevated levels positively correlated with the elevation seen in plasma PLA2 enzyme activity. The antibodies also have been used to purify immunoreactive PLA2 from plasma of patients with sepsis, thus enabling characterization of the purified protein by amino-terminal sequence analysis. We conclude from this study that the increase in PLA2 activity seen in association with sepsis and septic shock results from a dramatic elevation in levels of a circulating PLA2 enzyme. This inflammatory PLA2 is indistinguishable, both immunologically and chemically, from that associated with rheumatoid arthritis. Therapeutic agents directed towards inhibition of this inflammatory PLA2 enzyme may have utility in the treatment of both chronic and acute inflammatory disease. PMID- 1757124 TI - Extrahepatic expression of plasma protein genes during inflammation. AB - The body's protective responses to infection, wounding, trauma, and malignancy include the acute-phase reaction, which is modulated by various cytokines and their cellular receptors. During the acute-phase reaction, levels of specific proteins synthesized by the liver increase in the plasma. Little information is available about the extrahepatic synthesis of plasma proteins during the acute phase reaction. The study described here analyzes the tissue-specific expression of genes encoding the plasma proteins albumin (ALB), alpha 1-antitrypsin (AAT), transferrin (TF), haptoglobin (HP), ceruloplasmin (CP), serum amyloid A (SAA), alpha 1-acid glycoprotein (AGP) and alpha 2-HS-glycoprotein (AHSG) during the acute-phase reaction in C57B1 mice. The acute-phase reaction was induced by intraperitoneal injections of bacterial lipopolysaccharide (LPS). During the acute-phase reaction, genes encoding CP, SAA, AGP, and HP demonstrate unique extrahepatic tissue specific patterns of expression in kidney, spleen, thymus, heart, brain, lung, testis, and epididymis. Different temporal patterns of HP gene expression also were observed in lung and thymus after induction by LPS. The function of extrahepatic synthesis of plasma proteins is not yet understood; however, a local provision of specific plasma proteins in mammalian tissues may offer the host a source of functionally important proteins during periods of stress. PMID- 1757125 TI - Generation of xenopsin-related peptides from tissue precursors by media conditioned by endotoxin-stimulated rat peritoneal macrophages. AB - Incubation of media conditioned by endotoxin-stimulated rat peritoneal macrophages generates immunoreactive xenopsin (iXP) when incubated with acid extracts of various tissues of the rat. The generation of iXP, as measured by specific radioimmunoassay and confirmed by HPLC analysis, increased as the length of the incubation period increased and was inhibited by pepstatin, prior boiling of the conditioned media, or by omitting either the tissue extract or the conditioned media. The pH optimum for the generation of iXP was 3.0. The generated iXP showed biological activity in that stimulated histamine secretion from isolated rat mast cells and this secretory response was prevented by metabolically poisoning the cells. In addition, the generated iXP stimulated contraction of the isolated guinea pig ileum. In this regard, it was similar to neurotensin (NT). Tissue precursor levels for iXP, as measured by this system of generation, were highest in kidney, liver, and skin and lowest in skeletal muscle and plasma. These results suggest to us that during the inflammatory response, the NT-related peptide, xenopsin, can be generated from tissue precursor(s) by enzymes secreted by invading macrophages. The generated XP may then affect the participating cells of inflammation. PMID- 1757126 TI - Regulation of serum amyloid A gene expression in Syrian hamsters by cytokines. AB - Amyloid A (AA) protein is derived from serum amyloid A (SAA) and deposited as beta-pleated sheet fibrils in reactive amyloidosis, a disease that occurs spontaneously in golden Syrian hamsters. The precursor SAA is an acute-phase reactant in many species including hamsters, and in this report we have defined the in vivo kinetic and dosage responses for SAA mRNA accumulation in hamsters following administration of various cytokines. Elevations in levels of hepatic SAA mRNA were documented when the doses of interleukin-1, interleukin-6, and tumor necrosis factor were increased. The increase in dosages applied ranged from 2 1/2-fold for interleukin-6 to 10-fold for interleukin-1. SAA transcript levels were highest 8 h following administration of interleukin-6 or tumor necrosis factor, whereas maximal amounts of SAA-specific mRNA were found 24 h after administration of interleukin-1. PMID- 1757127 TI - Role of neutrophils in acetic acid-induced colitis in rats. AB - Intrarectal administration of 4% acetic acid produces diffuse inflammation that ultimately results in erosions and ulcerations of the rat colon. Although this model of colitis has been used extensively over the past several years, there are no quantitative data available regarding the relationship between neutrophil infiltration and mucosal injury during times of active inflammation. Therefore, the objective of this study was to define the role of extravasated neutrophils as mediators of mucosal injury and inflammation in acetic acid-induced colitis. We found the intrarectal administration of 4% acetic acid produced an 11-fold increase in colonic mucosal permeability, a 9-fold increase in colonic MPO activity, and a 1.6-fold increase in colon weight at 48 h following administration of acetic acid. In addition, we found significant correlations between colonic MPO activity and mucosal permeability and between colonic MPO activity and colon weight (P less than 0.01 for both). These data suggested that inflammatory neutrophils may mediate mucosal injury and inflammation in this model of colitis. To assess the role of circulating neutrophils, rats were rendered neutropenic for 48 h by the intraperitoneal administration of antiserum directed toward rat neutrophils (ANS). Although ANS treatment reduced both the number of circulating neutrophils and colonic MPO activity to less than 10% of control values, it did not attenuate the increases in colonic mucosal permeability nor did it attenuate the increases in colon weight produced by acetic acid. Histological inspection confirmed that ANS treatment was not effective in attenuating the injury to the epithelial barrier. These data demonstrate that infiltrating neutrophils do not mediate the mucosal injury and inflammation observed in acetic acid-induced colitis. PMID- 1757128 TI - Scavengers of reactive oxygen intermediates do not mediate the depression of macrophage hydrogen peroxide production caused by erythrocyte phagocytosis. AB - Our previous studies have shown that a phagocytic challenge with IgG-coated erythrocytes (EIgG) depressed macrophage triggered H2O2 production in vitro, and in vivo there was a decrease in the survival rate following bacteremia. The phagocytosis of an equal number of IgG-coated erythrocyte ghosts had none of these effects, indicating that the contents of the erythrocytes are important for these effects. The present study evaluated the role of the scavengers of reactive oxygen intermediates within erythrocytes in the depression of H2O2 production triggered with phorbol myristate acetate following a phagocytic challenge with EIgG. Elicited rat peritoneal macrophages (PM) were challenged with EIgG prepared from normal E or E with inactivated catalase, depleted glutathione, hemoglobin converted to methemoglobin, or fixed with formaldehyde. The depression of triggered H2O2 production was similar when equal numbers of normal EIgG and EIgG with inactivated scavengers were phagocytized. When the phagocytic challenge with normal EIgG was carried out in the presence of cytochalasin B, no depression of triggered H2O2 production was observed. Cytochalasin B partially blocked the phagocytosis of EIgG, so that with larger doses of EIgG there was sufficient ingestion of EIgG to depress H2O2 production in untreated PM. These results indicate that the scavengers of reactive oxygen intermediates present in erythrocytes are neither required nor sufficient to depress H2O2 production by macrophages. PMID- 1757129 TI - No effect of recombinant human interleukin-1 on numbers of peripheral blood and peritoneal leukocytes during acute inflammation. AB - Recombinant human interleukin-1 (IL-1) can prolong the survival of mice with severe systemic bacterial or fungal infections. In order to assess whether this is due to an effect of IL-1 on the production of leukocytes or their migration to the site of infection, the influence of IL-1 on the influx of leukocytes to the site of an acute inflammation was studied in normal and in granulocytopenic mice. The numbers of granulocytes, lymphocytes, and monocytes or macrophages in both the circulation and the peritoneal cavity were determined during an acute sterile inflammation elicited by intraperitoneal injection of either newborn calf serum (NBCS) or heat-killed Candida albicans, and during a peritoneal infection with viable C. albicans. After normal mice were injected intraperitoneally with NBCS or 10(7) CFU heat-killed or viable C. albicans, the number of peritoneal granulocytes rose sharply within 6 h. Pretreatment of mice with a single intraperitoneal dose of 80 ng IL-1 24 h before injection of an inflammatory stimulus did not influence the course of the numbers of leukocytes in the circulation or in the peritoneal cavity. When mice were rendered granulocytopenic by cyclophosphamide, both the influx of granulocytes into the peritoneal cavity and the concomitant rise in the number of peripheral blood granulocytes after injection of NBCS, killed or viable C. albicans was virtually absent. Pretreatment of granulocytopenic mice with IL-1 did not influence the course of the numbers of leukocytes in either the circulation or the peritoneal cavity. These findings show that the beneficial effect of a single dose of IL-1 on the course of candidal infections in normal or granulocytopenic mice is not attributable to the influx of granulocytes or monocytes. PMID- 1757130 TI - Modification of inflammatory processes by phenobarbital in rats. AB - Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this biological marker of inflammation or is capable of altering the clinical course of inflammatory processes. Local carrageenan injection induces a similar time dependent plantar edema and increases serum AGP levels in Sprague-Dawley (SD) and Dark Agouti (DA) rats. Pretreatment with PB for seven days modified neither parameter in SD rats while plantar edema was aggravated and serum AGP levels were increased in DA rats. The sedative-hypnotic properties of PB were not involved, since a single administration of this drug had no action in DA rats. On the other hand, chronic PB administration reduced the severity of an autoimmune disease, type II collagen-induced arthritis, in DA rats. These data indicate that PB, a potent inducer a cytochrome P-450-dependent enzymes, modifies the course of the inflammatory process. Preliminary results with macrophage transfer experiments suggest that this response to PB could be mediated by stimulated macrophages. PMID- 1757132 TI - Scaphoid fractures and wrist pain--time for new thinking. AB - As with the practice of all medicine, an early accurate diagnosis is essential. The same applies after injury. The diagnosis should be made at the earliest opportunity--this should be done as soon as an appropriate expert is able to examine the patient, assess adequate radiographs and, where necessary, order special investigations such as a bone scan. By this means, distal radial fractures, injuries of the radioulna joint, dislocated lunates, Bennett's fractures, dorsal capsular wrist sprains, avulsion fractures etc. can be managed accordingly. Those patients in whom clinical examination, plain radiographs and/or bone scans show minor injuries can be advised about pain relief whilst staying active either at work or in the home using a light supportive removable bandage or splint. Where doubt remains and whilst keeping the patient comfortable, a bone scan may be requested. Its availability together with updated clinical and, if necessary, radiological assessment, will define a further group of patients who can be advised definitively either about active treatment or a return to normal activity. Only a few wrists will continue to defy definitive diagnosis requiring the continuance of expert advice and investigation. When a scaphoid fracture is diagnosed, its site, degree of displacement and any associated instability should determine the degree of intervention and the length of time required in plaster. This again gives the patient more information about the long-term future than many have had hitherto. The patient's individual requirements may be taken into account; some are happy to tolerate 2-3 months in plaster whilst others want the early function which an uncomplicated operation might offer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757131 TI - Leukocyte elastase-independent proteolysis of gelatin-bound fibronectin by inflammatory macrophages. AB - Fragmentation of lung matrix fibronectin by proteases released from activated phagocytic cells has been implicated in lung vascular injury. We examined whether denatured collagen (gelatin)-bound fibronectin can be degraded by peritoneal exudate mononuclear phagocytes harvested from rats 96 h after intraperitoneal casein injection. Microtiter plates were pretreated with gelatin and then supplemented with purified 125I rat plasma fibronectin, which readily bound to the gelatin. Stimulated inflammatory exudate cells were added and proteolysis of the bound fibronectin was studied by the release of [125I]fibronectin fragments into the media. Following 2 h of incubation, peritoneal exudate mononuclear macrophages stimulated with opsonized zymosan released three times more radiolabeled fibronectin into the medium as compared to background controls, and 1.5 times more radiolabeled fibronectin as compared to cells not stimulated with zymosan. Western blot analysis and autoradiography confirmed the presence of fragments of fibronectin in the culture medium. Some of these fragments were clearly derived from the radiolabeled matrix, but others that were not labeled were potentially released directly from the added stimulated macrophages. The release of radiolabeled fibronectin was inhibited by N-p-tosyl-L-lysine chloromethyl ketone (TLCK), a trypsin specific inhibitor, but not by methoxysuccinyl-alanine-alanine-proline-valine-chloromethyl-ketone (AAPVCK), a leukocyte elastase-specific inhibitor. These results suggest that fibronectin bound to denatured collagen is susceptible to leukocyte elastase-independent enzymatic degradation by stimulated inflammatory exudate mononuclear phagocytic cells. Such proteolysis may mimic a pathological process associated with lung vascular injury during the sequestration of activated macrophages in the lung microcirculation and interstitium. PMID- 1757133 TI - Hepatic trauma and its management. AB - This review examines the current management of trauma to the liver. The incidence, mechanism, classification, diagnosis, treatment and complications of hepatic trauma are discussed. Diagnosis of hepatic injury may be difficult and specific investigations are suggested. Non-operative treatment and the strict criteria necessary to identify suitable patients for this are assessed. The recent trend to conservative surgery in hepatic trauma is reviewed. Aggressive resuscitation and early control of bleeding are crucial and are emphasized. PMID- 1757134 TI - Intracast pressure measurements in Colles' fractures. AB - Intracast pressures were recorded in conventional plaster-of-Paris below-elbow casts and compared with a new prefabricated brace for the functional treatment of Colles' fractures. Interface pressures were consistently higher in the brace than in the conventional plaster cast throughout the treatment period, and demonstrated more specific loading to the fracture site. PMID- 1757135 TI - Flexion supracondylar fractures of the humerus in children: treatment by manipulation and extension cast. AB - We have reviewed, at an average of 7 years, 14 children with flexion supracondylar fractures of the humerus. These fractures accounted for 6 per cent of the 288 displaced supracondylar fractures treated from 1981 to 1985. A total of 12 patients had typical fractures that were treated by manipulation and immobilization in an extension cast. Two patients had atypical fractures with anterior displacement and posterior angulation of the distal fragment; they were treated by manipulation, but were more stable when immobilized with the elbow flexed with strapping and collar and cuff support. Overall, excellent or good results were achieved in 10 cases and poor results in four cases. Of the poor results, two were due to cubitus varus. These children were the only ones under 2 years of age, and in each the deformity was due to the persistence of an abnormally large Baumann angle. Plaster immobilization was inadequate at this stage. The other two poor results were due to mild stiffness of the elbow. For typical fractures, we conclude that excellent results can be expected in most children over the age of 2 years when treated with manipulation and immobilization in extension for 3 weeks. For the rarer atypical fractures, we conclude that excellent results can be expected after manipulation and immobilization in flexion for 3 weeks. PMID- 1757136 TI - Supracondylar fractures of the humerus in childhood: range of movement following the posterior approach to open reduction. AB - The posterior approach for open reduction of supracondylar fractures of the humerus has been condemned for causing decreased elbow movement. This study investigates this by comparing the range of movement in children treated by posterior open reduction and Kirschner wiring with those treated by closed reduction and immobilization. A total of 65 children with severely displaced supracondylar humeral fractures have been reviewed. There was some loss of movement in 66 per cent of the open reduction group and 42 per cent of the closed reduction group. The proportion losing more than 10 degrees of movement was the same in both groups. The difference between the two groups was due to the increased numbers in the open reduction group who lost less than 10 degrees of motion. Posterior open reduction of childhood supracondylar fractures is not associated with an important loss of elbow movement and need not be avoided on this account. PMID- 1757137 TI - Fractures of the body of the hamate. AB - Eight cases of fracture of the body of the hamate are presented, with descriptions of the injury and management. This fracture may be considerably more common than indicated by standard texts and previous published reports. PMID- 1757138 TI - High-pressure injection injuries. AB - A retrospective review of the 11 patients attending the Hand Unit at the Derbyshire Royal Infirmary over the last 5 years with high-pressure injection injuries is presented. The machines and materials that cause these injuries are outlined and the methods of treatment and rehabilitation are described in detail. The study demonstrates the morbidity of high-pressure injection injuries, particularly those inflicted by paint spray guns, and highlights a frequent delay between injury and decompression of the injured part. We wish to emphasize the importance of early diagnosis, referral, exploration and rehabilitation to ensure an optimal outcome, and to point out that failure to refer early is becoming an increasing focus of negligence claims. PMID- 1757139 TI - Urinary tract injuries in multiply-injured patients: a rational guideline for the initial assessment. AB - In a retrospective study involving 866 multiply-injured patients we demonstrated urinary tract injuries in 72 patients (8.3 per cent), 17 (2 per cent) of which were serious. Haematuria was a frequent finding in multiply-injured patients. In patients with serious lesions of the urinary tract, more than 35 RBCs/HPF in the sediment or macroscopic haematuria were found. All major injuries were demonstrated by the emergency intravenous urogram. Ultrasonography demonstrated contusions of the kidney or bladder and ruptures of the kidneys, but was not reliable in diagnosing ruptures of the bladder. Of 155 patients with a pelvic fracture 13 (8 per cent) had lower urinary tract injuries. In all these patients the fracture was located in the pubic arch. If a retrograde urethrogram was performed in these patients all urethral lesions were detected. We propose a rational guideline, which guarantees diagnostic accuracy of serious injuries of the urinary tract after blunt trauma, while interfering as little as possible with the resuscitative and diagnostic procedures in severely injured patients. PMID- 1757140 TI - Delayed diagnosis of injuries from the M1 aircraft accident. The Nottingham, Leicester, Derby, Belfast Study Group. AB - The incidence of a delay in the diagnosis of injuries from the 83 survivors of the M1 aircraft accident is described. A total of 32 injuries in 25 patients were not initially diagnosed, nine each in the upper and lower limbs and 14 in the spine. This was equivalent to 9.6 per cent of all the major injuries suffered by the survivors. Five patients required surgery for a late diagnosed injury. The incidence of a delayed diagnosis injury (DDI) was not related to the overall severity of injury. Delay in diagnosis of injuries after such a major accident was attributable to failure of clinical examination, failure to radiograph symptomatic areas and failure of radiographic interpretation. PMID- 1757141 TI - Proximal radioulnar translocation in association with posterior dislocation of the elbow. AB - Proximal radioulnar translocation in association with posterior dislocation of the elbow in childhood is a very rare injury. The aetiology is considered to be iatrogenic, resulting from an inappropriate reduction technique. Two cases are described that challenge this view. A mechanism of injury to explain translocation at the time of injury is proposed. PMID- 1757142 TI - Stress fracture of the first rib without associated injuries. PMID- 1757143 TI - Isolated fracture-dislocation of the proximal radius. A previously undescribed injury. PMID- 1757144 TI - Late carpal instability associated with dorsal distal radial fracture. PMID- 1757145 TI - A combined flexion-extension injury of the atlanto-axial complex. PMID- 1757146 TI - An unusual fracture of the atlas. PMID- 1757147 TI - Compartment syndrome after intramedullary interlocking nailing of a tibial fracture. PMID- 1757148 TI - Traumatic cerebrospinal fluid rhinorrhoea: a timely reminder. PMID- 1757149 TI - Delayed Serratia marcescens osteomyelitis following a gunshot injury. PMID- 1757150 TI - An unusual presentation of papillary carcinoma of the thyroid gland. PMID- 1757151 TI - A wrench, a crutch and a nail. PMID- 1757152 TI - A simple method to improve wound care for a windowed plaster. PMID- 1757153 TI - Three simple surgical aids. PMID- 1757154 TI - Using ultrapure water in hemodialysis delays carpal tunnel syndrome. AB - Since 1977, our patients have undergone chronic HD with ultra-pure dialysate (UPD), defined as having endotoxin levels below 0.008 ng/ml and less than 1 bacteria/ml of dialysate. We evaluated the incidence of carpal tunnel syndrome (CTS) in three groups of patients. Group I (GI), 84 patients, dialysed for 6.1 +/ 3.2 years (mean +/- SD) with UPD only; Group II (GII), 39 patients, first dialysed for 3.7 +/- 2.3 years with non-UPD and afterwards for 8.4 +/- 2.1 years with UPD; Group III (G III), 103 patients treated for 6 +/- 5.9 years exclusively with non-UPD. All patients were dialysed with cuprophan or cellulose acetate membranes. Results, expressed by Kaplan-Meier actuarial survival curves as the percent of patients without CTS, show that CTS occurred significantly less in GI than in GIII. This may be due to less stimulation of monocytes resulting from the absence of bacteria, endotoxins and pyrogens in the dialysate, which would reduce the stimulation of cytokines release, interleukin 1 and 6, and tumor necrosis factor, known to stimulate beta 2 microglobulin synthesis. PMID- 1757155 TI - Filtration of dialysate using an on-line dialysate filter. AB - Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3 hour test period. Bacterial and endotoxin levels on the input side of the first stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins. PMID- 1757156 TI - Adherence of blood cells to dialyzer membranes as a measure of biocompatibility. AB - Cell adherence to plate dialyzer membranes was analyzed at the end of 4 hours of dialysis. Three types of membranes were examined: Cuprophan Hemophan and Gambrane, (a polycarbonate membrane). The membranes were mounted in dialyzers that contained 23 layers of one membrane type and one layer of each of the two other. Less leukocytes adhered to the Pc than to the Cu and He membranes. Transient initial complement activation during dialysis, which was considerably lower with dialysers containing mainly Pc membrane, was not correlated to adherence of cells to the membranes. Instead flow geometry is proposed as the main factor determining the adherence. Contrary to what has been earlier suggested, we think that leukocyte adherence is not a very suitable measure of membrane biocompatibility. The reason is that the influence of membrane surface chemical factors can not be separated from mechanical factors due to the design of the device. PMID- 1757157 TI - In vivo demonstration of the Haldane effect during extracorporeal gas exchange. AB - During the extracorporeal support (LFPPV-ECCO2R) of 11 patients suffering from severe lung failure (ARDS), we consistently noticed a higher arterial than mixed venous PCO2 in blood samples drawn at the same time. Two explanations are possible: a) the Haldane effect (HE), b) CO2 from lung tissue metabolism. In order to distinguish changes in PCO2 due to the HE from those due to tissue CO2 production, CO2 content (CCO2) was calculated. The results were compared to animal experiments with hyperoxic apnea, after which arterial and mixed-venous samples were drawn simultaneously. All blood gas samples were analyzed for pH, PCO2, PO2, and O2-saturation, from which CCO2 was calculated. In both groups, PaCO2 was 2.15 mmHg (2.7 mmHg respectively) higher at a lower CaCO2 (-2.87 ml/l, 14.9 ml/l). Oxygen saturation increased by 8.1% in the human group and 17.8% in the animal group. A significant relationship was found between changes in PCO2 and changes in O2-saturation. This is a demonstration of the Haldane effect. PMID- 1757158 TI - Cardiac output requirements and maximum dimensions for a neonate total artificial heart. AB - Two equally important issues need to be addressed during the early stages of the design of an implantable total artificial heart (TAH): proper anatomical fit and cardiac output capacity. As part of a first-time feasibility study to develop a neonate-size TAH, two studies were conducted to establish useful anatomical and physiological standards. The first (Study A) was conducted to determine the maximum dimensions of a neonate-size TAH. Twelve preserved hearts from full-term neonates with the hypoplastic left heart syndrome were examined. A second study (Study B) was designed to determine the acceptable minimum stroke volume compatible with minimum neonate cardiac output requirements. This study was based on a combination of: a) reported cardiac output studies in healthy term neonates, and term neonates with heart failure, b) body weight range, and c) limiting factors of TAH technology, e.g., valvular regurgitation and leveling off of the maximum cardiac output value at a specific heart rate and filling pressure. The proposed neonatal standards for TAH technology are presented. PMID- 1757159 TI - Shear stress related blood damage along the cusp of a tri-leaflet prosthetic valve. AB - Blood flowing through a prosthetic heart valve can be damaged by flow-induced shear forces. Fluid dynamics variables and geometric factors play an important role in the evaluation of shear-stress-related blood damage. Central-flow prosthetic valves have been considered as an optimal replacement for mechanical and biological valves. Recently it was shown that shear stress distribution along the surface of a polyurethane cusp reaches values that can damage the blood elements. A mathematical model correlating the effects of shear stresses on blood corpuscles with clinical findings was employed in vitro. The model can be applied to the effects of blood-surface interaction and is of clinical relevance. PMID- 1757160 TI - Heparin-coated versus non-coated surfaces for extracorporeal circulation. AB - Studies were made to compare completely heparin-bonded (HBS) and conventional extracorporeal circulation surfaces using capillary membrane oxygenators (CMO) in sheep and dogs for up to five days. The aims were: to investigate the need for systemic heparinization in the case of heparin-coated surfaces, to assess blood compatibility and gas exchange performance of both systems and the extent of complement activation, and to find solutions for plasma leakage by the use of CMO. All studies were performed under standardized conditions, such as drugs, surgery, priming, blood flow rate etc. For heparin-coated surface studies all blood interfaces (CMO, catheters, tubes, etc) were coated. It was possible to eliminate systemic heparinization totally when HBS were used. During the five-day non-heparin application period blood coagulation parameters were almost unchanged and in the physiological range, platelets did not drop below 80%, hemolysis was negligible and gas exchange performance was unaffected. Less complement activation occurred with HBS than with non-coated surfaces. PMID- 1757161 TI - An insulin-releasing system responsive to glucose: thermodynamic evaluation of permeability properties. AB - Two weak poly(acid)s, poly(acrylic acid) (PAA) and poly(N-acryloyl-glycine) (P1), were graft-copolymerized onto porous cellulose membrane and their protonation behavior in aqueous media was studied by potentiometric techniques. Comparison with the corresponding free polymers in solution showed the same basicity constants during the protonation of ionized carboxyl groups, and the large potentiometric hysteresis loops observed for the grafts were indicative of specific interactions with the cellulose substrate. This was confirmed by FT-IR spectroscopic analysis at low pH. The polymeric membrane system, containing immobilized glucose oxidase, was synthesized for the purpose of insulin delivery in response to glucose concentration. The porosity of the membrane was controlled by the charge-state conformations of the grafted chains. The formation of gluconic acid in the presence of glucose caused a drop in pH which led to neutralization of the negatively charged carboxyl groups. The decrease in electrostatic repulsion caused the extended macromolecular chain to assume a coil like form and opened the membrane pores to insulin. PMID- 1757162 TI - Effect of neo red cells on the canine hemorrhagic shock model. AB - This study evaluated the newly developed artificial red blood cells named Neo Red Cells (NRC) after hemorrhagic shock in mongrel dogs. NRC is prepared as microcapsules by a method in which stroma-free hemoglobin is encapsulated using a bimolecular lipid membrane called liposome. The particle size is 0.2 micron, methemoglobin content is less than 5% and the hemoglobin concentration is 5.6 g/dl. We analyzed blood gases and hemodynamics and carried out laboratory examinations after 59-88% blood exchange using NRC. The hemodynamic parameters returned to the normal range after NRC. Inhaling normal room air, oxygen carried by NRC was 60.40% at the exchange rate of 88%. Renal and hepatic function and other laboratory findings were normal after administration of NRC. After further study and improvement NRC could be considered suitable as artificial blood for treatment of hemorrhagic shock. PMID- 1757163 TI - OASYS: a computerized auditing system for orthopaedic surgery. AB - Medical auditing based on individual diagnoses or specific therapies is well established. Auditing of all medical activity has an expanding role in quality assurance and research. In an attempt to overcome the limitations of existing auditing systems, a fundamentally different, flexible, high quality and easily accessible orthopaedic auditing system has been developed. This records a description of each component of patients' orthopaedic diagnoses, records treatment and complications, produces discharge letters and surgical log books and allows flexible and comprehensive audits. It has been in use in an orthopaedic service since January 1990 and has been successful in identifying problems and monitoring the effectiveness of changes. It is anticipated that the system will become more widely used and provide the basis for a 'user group' which will share the accumulated data and further development costs. PMID- 1757164 TI - Segmentation of brain CT images using the concept of region growing. AB - A method is described for extracting and isolating cerebrospinal fluid and tissue areas of brain images obtained with computed tomography. The classification of the pixels into components is based on region growing and nearest neighbor principles. To aid the performance of this method, the algorithm utilizes a priori information on the anatomic composition of the brain, and reduces the 'cupping effect' in the CT image that is attributed to beam hardening artifacts. In order to avoid subjectivity, the performance of the algorithm was tested by superimposing five computer-simulated circular lesions on different areas of the original CT scans, 8 mm thick. These images were taken at different levels in the brain, thereby accommodating different anatomy as well as the apical artifact of CT scanning. In this exploratory investigation, the false negative error of segmentation for lesions having diameter of 20 pixels was found in the order of 25% at an estimated partial volume (PV) effect of 50% that decrease further to about 5% for a PV of 80%. At that point the false positive error becomes the dominant error in the analysis. PMID- 1757165 TI - Modeling autostimulation of growth in multicellular tumor spheroids. AB - We report the development of a growth model that includes the positive regulatory feedback by cell-cell interactions. It is based on the model by Wheldon et al. (J Theor Biol, 38 (1973) 627) and Cox et al. (Comput Biomed Res, 13 (1980) 445) and is characterized by biologically interpretable parameters. We applied the model to growth of multicellular spheroids formed by V79 Chinese hamster fibroblasts. The new model resulted in a statistically sound fit. We compared the applicability of our model, of the model by Wheldon et al. and Cox et al. as well as of the related model by Piantadosi (Comput Biomed Res, 18 (1985) 220). We affiliated the models with each other within a nesting scheme and compared their respective fits to data by the F-test. Our model yielded a fit statistically equivalent to the fit by the model of Piantadosi. However, in distinction to other models, the estimated cellular doubling time in our model agreed better with the respective experimentally determined value. PMID- 1757166 TI - Stability and bifurcation of a reaction-diffusion system. AB - In this paper we study the stability and bifurcation of partial differential equations derived from enzyme immobilisation modelling. Sufficient mathematical conditions ensuring stability and bifurcation are obtained. PMID- 1757167 TI - A computerized system for measuring time perception in human subjects. AB - We describe an integrated computerized approach to the design, execution and recording of time perception experiments in human subjects. The program is menu driven and runs on an IBM-compatible microcomputer. The method is easy to use, non-obtrusive to the subjects, and flexible enough to allow the investigator to design studies with a wide range of experimental protocols and study parameters. The fact that the results do not depend on proctor bias or subject-proctor interactions are additional advantages. The technique was applied to study the effects of prompt positive feedback on the time perception of normal human subjects who undergo training. The results of this study are reported. PMID- 1757168 TI - From Ganja to crack: Caribbean participation in the underground economy in Brooklyn, 1976-1986. Part 1. Establishment of the marijuana economy. AB - The involvement of Caribbean youth in drug distribution (marijuana from the mid 1960s to 1981; cocaine hydrochloride powder and crack from 1981 to 1987, the time of writing) throughout the Circum-Caribbean area and in North America is described. Social, economic, and cultural outcomes of these engagements are highlighted, and the relationship between the underground economy of drugs and the corporate, capitalist economy is explored. Responding to high rates of unemployment and to other problems of migrant adaptation, young Caribbean African males established a multimillion dollar marijuana (ganja) trading network which linked cultivators on the islands with exporters/importers and street-level distributors in North American cities. By 1976, its participants had become Rastafarians, or followers of an ideology of self-reliance and indigenous development. Following its precepts, they reinvested marijuana revenues to revive cottage industry and agriculture. In Caribbean or minority neighborhoods, therefore, marijuana was a "positive vibration" and its distributors were lionized. PMID- 1757170 TI - Psychometric evaluation of the Children of Alcoholics Screening Test (CAST) in a psychiatric sample. AB - The Children of Alcoholics Screening Test (CAST) is a 30-item screening instrument developed to identify children who are either living with or have lived with alcoholic parents. In a sample of 250 psychiatric patients, the CAST exhibited substantial item-total scale correlations and a high level of internal consistency reliability. Total CAST scores discriminated self-identified children of problem drinkers from control subjects and were significantly correlated with the severity of parental psychological and social complications due to alcohol misuse. Factor analysis indicated a unidimensional scale structure. CAST cut-off scores produced a low false positive and false negative rate. The psychometric properties of the CAST suggest that it is a useful screening instrument for identifying the offspring of problem drinkers and alcoholics. PMID- 1757169 TI - Outcomes of an AIDS prevention program for methadone patients. AB - Methadone maintenance patients are at risk of contracting or transmitting HIV through intravenous drug use and/or unsafe sexual practices. An outcome evaluation of a voluntary AIDS prevention program for methadone patients in three clinics (two experimental, one control) is reported. The prevention program included three components: didactic AIDS education, HIV antibody counseling/testing, and facilitated peer support groups. Participation in AIDS education was associated with increased knowledge of AIDS risks and with improved attitudes toward condoms. Peer group participation was associated with improved attitudes toward the use of condoms and with increased use of condoms. Learning of HIV seronegativity was related to increased self-efficacy and decreased intravenous drug use risk behaviors. Rates of participation in the prevention program were disappointing, but the program seemed beneficial for those patients who did become involved. PMID- 1757171 TI - Alcohol, age, and piloting: judgement, mood, and actual performance. AB - We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching .04 g/dL (.04%) BAL, after .10% BAL, and then 2, 4, 8, 24, and 48 h after .10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve. PMID- 1757172 TI - A comprehensive worksite smoking control, discouragement, and cessation program. AB - The effectiveness of a comprehensive program of worksite smoking control, discouragement, and cessation was compared with a program of smoking cessation alone. Two comparable oil refineries served as the research sites. Outcome variables consisted of employee self-reported smoking rate assessed by the use of a smoking questionnaire and unobtrusive observations of smoking behavior before and after the intervention. One company was randomly assigned to the comprehensive program of smoking control, discouragement, and cessation while the other company only received smoking cessation. Humorous antismoking posters emphasizing the benefits of quitting smoking were distributed throughout the first worksite and changed every 2 weeks. Large banners stating "Go SmokeFree" were also placed at all locations to this plant and left up for the duration of the study. Three weeks after the initiation of the smoking discouragement program at one refinery, a group smoking cessation program was begun at both plants. At a 5-month follow-up, participants in the smoking cessation treatment at the plant receiving the comprehensive program achieved a 5-month abstinence rate of 43% in comparison with a rate of 21% at the refinery receiving only smoking cessation. PMID- 1757173 TI - An application of mathematical models for decision making to the selection of policies on testing for drug use. AB - The object of the paper is to provide the basis to decide whether testing for drug use should be used, taking into consideration individual and social benefits and costs that the results of the tests could originate. In the analysis, special attention is paid to the fact that the actual costs of the tests themselves are not the most important elements of the social costs of a testing program. The most important costs are those generated by the defective results of the tests. They can provide false positive results, meaning that a nonuser is identified as a user, or false negative results in which a user is not identified as such. Social costs of the false positive results range from lowered worker morale to legal suits, while the false negative results eliminate any benefit that the identification of drug users could have. Combining all these elements, Correa and Woods specify a mathematical procedure as a decision tool to be used for determining whether a testing program should be implemented in specific industries or groups of industries. A complete implementation of the model is not carried out due to the lack of the required statistical information. However, preliminary trials showed that the conceptual and mathematical framework is operational, and that the model prepared could be used as a guideline for collecting the most appropriate data for decision making. PMID- 1757174 TI - Alcohol and psychiatric illness: longitudinal study of psychiatric admissions in a cohort of Swedish conscripts. AB - The association between level of alcohol consumption and admission for psychiatric care during a 15-year follow-up was studied in a cohort of 49,464 Swedish conscripts. The relative risk for psychiatric admission among high consumers of alcohol (more than 250 g alcohol per week) was 5.3 (95% confidence interval 4.7-6.0) compared with moderate consumers (1-100 g alcohol per week). After control for social background variables in a multivariate model, the odds ratio was 1.8 (1.5-2.1). Abstainers had the same rate of admission as moderate consumers. The association with alcohol was positive in all diagnostic categories studied. Neurotic depression was found to be a risk factor for admission for alcoholism, indicating that a causal association between alcohol and neurotic depression may go in both directions. PMID- 1757175 TI - Common pathways for epidermal growth and inflammation and their relevance in the pathogenesis of psoriasis. PMID- 1757176 TI - Pre-emptive diagnosis of leprosy. PMID- 1757177 TI - Leprosy in the United States. Just a curiosity? PMID- 1757178 TI - To compound or not? That is the question. PMID- 1757179 TI - Heat shock proteins in cutaneous disease. PMID- 1757180 TI - Characterization of circulating lymphocytes by monoclonal antibodies in childhood and adult leprosy. AB - Peripheral blood lymphocyte assays using monoclonal antibodies were done in 66 patients with leprosy, consisting of 25 children and 41 adults. The results were statistically analyzed for correlations, if any, among the different age groups and matched controls. The results, however, failed to show any significant correlation, nor was it possible to draw any conclusion as to why the disease spectrum in children tends to be incomplete (ie, there is a low incidence of the highly bacilliferous form of disease expression). PMID- 1757181 TI - Cutaneous eruptions in Indian tick typhus. AB - Although frequently unrecognized, rickettsial infections may be an important cause for fever and exanthem in persons presenting to physicians in South India. Most often these patients are referred to dermatology departments with a diagnosis of "drug eruption." In the current study the authors analyzed 12 cases of rickettsial fever that were seen in the dermatology department of St. John's Medical College Hospital, Bangalore, between 1985 and 1989. The distinctive cutaneous eruption was found to be an important clue to an early clinical diagnosis. Specific serodiagnosis enabled us to confirm that Indian tick typhus, a member of the spotted fever group, was the most frequent cause for rickettsial fever presenting at our hospital. PMID- 1757182 TI - Nodular secondary syphilis. PMID- 1757183 TI - Papular pruritic eruption with human immunodeficiency virus infection. PMID- 1757184 TI - Cutaneous nocardiosis and human immunodeficiency virus infection. PMID- 1757185 TI - Topical canrenoic acid. Quantification of the antiandrogenic activity in the hamster flank organ. AB - The topical antiandrogenic activity of potassium canrenoate (CAK), compared with that of spironolactone (SP), was assayed in vivo in female golden Syrian hamsters whose flank organs were stimulated by subcutaneous administration of testosterone propionate. Sebaceous glands and hair were measured by a computerized image analyzer. Pigmented spots, sebaceous gland areas, and the diameter of hairs of the treated flank organs were smaller in the groups that received CAK (1.6 mg/day) and SP (0.4 mg/day). The authors' results showed that CAK may act as a topical antiandrogen on the hamster flank organ when applied in concentrations four times greater than the minimal active dosage of SP. Potassium canrenoate may be a useful weak topical antiandrogen, and it could be used in androgen-related skin disorders involving both sebaceous glands and hair, especially in men. These concentrations could be verified by additional clinical investigations. PMID- 1757186 TI - Extracorporeal photochemotherapy in the treatment of cutaneous T-cell lymphoma. Complexity of objective evaluation. AB - The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizarre lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8 methoxypsoralen (8-MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fulfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clinical responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer. PMID- 1757187 TI - How leprosy is depicted in Ben-Hur. PMID- 1757189 TI - To compound or not depends on. PMID- 1757188 TI - Human leukocyte antigen in bullous pemphigoid. PMID- 1757190 TI - Stimulated chemotactic response in neutrophils from Trichinella pseudospiralis infected mice and the neutrophilotactic potential of Trichinella extracts. AB - During infection with Trichinella pseudospiralis a strong neutrophil response is evident in the peripheral circulation of the mouse. This study compared the chemotactic response of neutrophils from uninfected, T. pseudospiralis-infected and Trichinella spiralis-infected mice to extracts from adult worms, newborn larvae and muscle-stage larvae of both species of parasite. The chemotactic response of neutrophils from T. pseudospiralis-infected mice to Zymosan-activated mouse serum (ZAMS) was significantly greater than that seen with neutrophils from either uninfected or T. spiralis-infected mice. Unstimulated chemotactic response of neutrophils from these three groups of animals to medium alone was similar. The chemotactic response of neutrophils from the three groups of animals was unaffected by either the concentration or source of serum. The chemotactic response of neutrophils from T. pseudospiralis-infected mice was significantly greater than that observed with cells from uninfected or T. spiralis-infected mice. Among parasite extracts, those from newborn larvae displayed the strongest chemotactic potential for neutrophils. Extracts from muscle larvae of T. spiralis and T. pseudospiralis and extracts of T. spiralis adult worms showed the weakest attraction for neutrophils. Extracts from adult T. pseudospiralis and from newborn larvae of both species elevated the chemotactic response of uninfected mouse neutrophils to a significantly greater level than that seen with ZAMS alone, while a significant reduction in this response was evident only when ZAMS was presented to neutrophils with 500 micrograms of extract from muscle larvae of T. pseudospiralis or T. spiralis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757191 TI - Immunity to Haemonchus contortus and the cellular response to helminth antigens in the mammary gland of non-lactating sheep. AB - Cellular exudates induced by infusion with helminth antigens were examined in non lactating mammary glands of ewes immune to infection with the abomasal nematode, Haemonchus contortus. Secondary immunological responsiveness was expressed in two ways. Firstly, antigens from adult H. contortus elicited larger eosinophil-rich cellular exudates in immune compared to non-immune ewes. In this situation, secondary responsiveness in the mammary gland must have been generated through abomasal infection with the parasite. Secondly, repeated infusion with the antigens from adult H. contortus increased the size of cellular exudates in both immune and non-immune ewes. Eosinophils predominated but numbers of macrophages and lymphocytes were also increased. In this second situation, secondary responsiveness must have been either supplemented in immune ewes or derived completely in non-immune ewes by contact with helminth antigens through the mammary gland. The helminth antigens which induce eosinophil exudates in the mammary gland may not be potently protective against H. contortus. Furthermore, eosinophil exudation may not be an in vivo correlate of immunity which is directly useful for discriminating protective antigens and applicable to vaccine development. Infusion with antigens from adult forms of either H. contortus or Trichostrongylus colubriformis elicited cellular exudates equally well in immune ewes primed by infusion with H. contortus adult antigens 7 days beforehand. In addition, antigens from infective larvae of H. contortus elicited cellular exudates more potently than antigens from adult worms. However, vaccination with irradiated larvae has shown that species-specific protective immunity for H. contortus is stronger than cross-protective immunity conferred by T. colubriformis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757192 TI - Pyridoxal 5'-phosphate dependent enzymes in the nematode Nippostrongylus brasiliensis. AB - Eight classes of pyridoxal 5'-phosphate dependent enzymes have been investigated in Nippostrongylus brasiliensis in parallel with rat tissues. The range of decarboxylases detected in N. brasiliensis was limited in comparison with rat tissues. N. brasiliensis possessed a highly active L-serine hydroxymethyltransferase, but in contrast with rat liver, 5-aminolevulinic acid synthetase was absent. Similar levels of L-serine and L-threonine dehydratase activities were detected in N. brasiliensis and rat liver, and both organisms lacked L-alanine racemase, L-tryptophan synthetase and L-methionine gamma-lyase. The demonstration of cystathionine beta-synthase and gamma-cystathionase in N. brasiliensis suggests the presence of a functional trans-sulphuration sequence. The substrate specificities of the nematode cystathionine beta-synthase and gamma cystathionase varied significantly from those of the corresponding mammalian enzymes. Particularly striking was the ability of N. brasiliensis cystathionine beta-synthase to catalyse the non-mammalian 'activated L-serine sulphydrase' reaction (L-cysteine + R-SH----cysteine thioether + H2S). N. brasiliensis and rat liver exhibited comparable abilities to transaminate amino acids via the 2 oxoglutarate: glutamate system. PMID- 1757193 TI - Development, survival, fecundity and behaviour of Haemaphysalis (Kaiseriana) longicornis (Ixodidae) at two locations in southeast Queensland. AB - The free-living stages of the tick Haemaphysalis (Kaiseriana) longicornis were studied at Mt Tamborine (526 m altitude) and Amberley (25 m altitude) in southeast Queensland between 1971 and 1980. Data are presented on the number of eggs and larvae produced, the moulting success of engorged larvae and nymphs and the survival and behaviour of unfed larvae, nymphs and adult females. Temperature, moisture, daylength, grass length and age of unfed ticks were investigated as sources of variation in development rates, fecundity or survival. At Mt Tamborine the life cycle was well synchronized with the seasons to produce one generation per year. At Amberley higher temperatures accelerated development rates and would have delayed diapause, so disrupting the life cycle. PMID- 1757194 TI - NADH oxidase and fumarate reductase of Ancylostoma ceylanicum. AB - Ancylostoma ceylanicum, the hookworm parasite of cat, dog and man, was found to contain NADH and/or NADPH oxidase as well as fumarate reductase activities. Both the enzyme systems were predominantly located in the membranes of mitochondrial rich preparations. The membranes also exhibited the presence of a reduced pyridine nucleotide transhydrogenase activity which transferred hydrogen from NADPH to NAD. Amongst respiratory inhibitors, rotenone (Site I inhibitor) markedly depressed both NADH oxidase and fumarate reductase while others, namely antimycin-A, KCN and azide, had a lesser effect. PMID- 1757195 TI - Purification of Gnathostoma spinigerum specific antigen and immunodiagnosis of human gnathostomiasis. AB - Specific antigen of G. spinigerum which has been shown to be a protein with a relative mol. wt of 24,000 (24K) was prepared from the advanced third-stage larvae (L3) obtained from the livers of naturally infected eels. The L3 were ground and extracted with water. Purification procedures involved gel filtration, chromatofocussing and anion exchange column chromatographies, while characterization of the specific antigen was performed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and staining, Western blot analysis and isoelectric focussing. The specific antigen which has a pI of 8.5 was used as antigen in the indirect enzyme-linked immunosorbent assay (ELISA) to detect specific antibody in four groups of individuals, namely five parasitologically diagnosed gnathostomiasis patients (group 1); 15 clinically diagnosed gnathostomiasis patients (group 2); 136 patients with other parasitic infections (group 3); and 25 normal healthy parasite-free controls. Sensitivity, specificity and predictive values (positive and negative) of the assay were 100%. PMID- 1757196 TI - Effects of cholinergic drugs on longitudinal contraction in levamisole susceptible and -resistant Haemonchus contortus. AB - A novel force transducer was used to measure the effects of cholinergic agonists on longitudinal contraction in Haemonchus contortus. Drugs were applied to whole worms or injected via a cannula in the pseudocoelomic cavity. A number of agonists, including nicotine and the anthelmintics m-aminolevamisole, levamisole and morantel, caused contractions in whole worms. Four- to 25-fold increases in concentration of the active compounds were required to cause contractions in each of two levamisole-resistant strains of H. contortus. Of the other compounds tested, bephenium had equivalent activity against susceptible and resistant strains. Anticholinesterase compounds caused contractions after a slight delay in susceptible, but not resistant worms. Numerous cholinergic agonists and other compounds did not cause contraction when applied to whole worms. One of these, acetylcholine, caused contractions in cannulated worms. Compared with the susceptible strain, five- to six-fold higher concentrations of acetylcholine were required to cause equivalent contractions in the resistant strains. Levamisole resistance in adult H. contortus is likely to be due to a change in the characteristics of the cholinergic receptor(s). PMID- 1757197 TI - Response of pre-adult and adult stages of Trichuris muris to common anthelmintics in mice. AB - The common anthelmintics, oxantel, mebendazole, albendazole and pyrantel were assessed for their comparative activity against Trichuris muris in mice. Mice were infected with T. muris and the infection was maintained by a brief cortisone administration during the second week of infection. Mice carrying the infection with different life cycle stages, viz. fourth stage larvae (L4), pre-adult and adult stages were dosed with anthelminitics. The worm burdens in control infection groups varied although infection dose and other conditions were uniformly followed. With various dose regimens tested, oxantel was highly potent; it eliminated completely pre-adult and adult stages, respectively at 25 and 12.5 mg kg-1 dose levels with significant activity also against adult worms at a 1.56 mg kg-1 dose level and against pre-adults at a 6.25 mg kg-1 level. Pre-adults required twice the dose given to that of adults for complete (100%) activity. Mebendazole was the next most active; a dosage of 37.5 mg kg-1 was completely active against pre-adults whereas a dosage of 2 x 50 mg kg-1 was required for complete elimination of adult worms. In addition, about 90% of the worms were eliminated with a single dose of 150 mg kg-1. However, a significant activity was seen against adults at a 25 mg kg-1 level and pre-adults at 37.5 mg kg-1, the lowest level tested. In comparison, albendazole did not induce complete clearance of pre-adult and adult stages even when tested at dose levels as high as 150 and 2 x 75 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757198 TI - Ultrastructural observations on the tegument and associated structures of the monogenean Cichlidogyrus halli typicus (Price & Kirk, 1967) Paperna, 1979. AB - The tegument of the ancyrocephaline monogenean gill parasite Cichlidogyrus halli typicus is basically similar to that of other monogeneans. However, there are some tegumental features shared with relatively few other monogeneans, namely the presence in the surface tegument of extensive regions of homogeneous granular cytoplasm, a close association between myofibres and the basal region of the tegument and the production of two different tegumental secretory bodies by the same cyton. It is suggested that the regions of homogeneous granular cytoplasm found in the troughs between the circular muscle fibres provide some kind of support for the tegument, perhaps related to contraction of the tegumental circular muscle fibres and body shape changes. Three kinds of transtegumental sensory structures are recognized, namely a uniciliated bulb, a bulb bearing a non-ciliary process and a non-ciliated bulb. The latter two kinds are reported for the first time in monogenans. Possible functions of these sensory structures are discussed. PMID- 1757199 TI - Concurrent infections of Echinostoma caproni and Echinostoma trivolvis in ICR mice. AB - ICR female mice, 6- to 8-weeks old, were exposed concurrently to 25 metacercarial cysts of Echinostoma caproni and 25 metacercarial cysts of Echinostoma trivolvis and necropsied 10 and 14 days post-infection. Controls consisted of mice exposed singly to either 25 or 50 E. caproni or E. trivolvis cysts. All 23 mice exposed to E. caproni cysts were infected with a total of 331 worms (37.8%), whereas only 11 (37.9%) of 29 mice exposed to E. trivolvis cysts were infected with a total of 77 (6.4%) worms. In the concurrent infections, 13 (59.1%) of 22 mice were infected with both species and the percentage of worm recovery was 72.6% for E. caproni and 14.2% for E. trivolvis. There was no difference in worm distribution of either species in single vs concurrent infections. In concurrent infections at 14 days PI, there was a significant decrease in the body area of worms of both species, when compared to single worm species. PMID- 1757200 TI - Molecular analysis of T and B cell repertoires in mice immunized with Opisthorchis viverrini antigens. AB - B10 mice were immunized with an Opisthorchis viverrini somatic extract and then their responses were analyzed. The antigenic fractions of the extract were separated by SDS-polyacrylamide gel electrophoresis, electroblotted to nitrocellulose membranes and solubilized for use in lymphocyte culture. Antibody specificity was also visualized by immunoblotting using immunized mouse sera. The Mr of the main immunogenic fractions for T cells ranged from 28 to 46 kDa, whereas those recognized by antibodies were 45, 52, 56, 59, 65, 69, 75 and 81 kDa. The results indicate a striking difference in the antigenic recognition pattern of T and B cells which may be important for selecting antigen molecules for immunological studies of this trematode infection in man. PMID- 1757201 TI - A Blastocystis species from the sea-snake, Lapemis hardwickii (Serpentes: Hydrophiidae). AB - Observations were made on Blastocystis isolated from the sea-snake, Lapemis hardwickii. Exponential growth of the organism was observed between 2 and 4 days of culture. Vacuolated, amoeboid and granular forms were observed in cultures, similar to B. hominis. The optimal growth temperature for the sea-snake Blastocystis was 24 degrees C compared with 37 degrees C for B. hominis. The karyotypic patterns of B. hominis and the sea-snake Blastocystis were studied in the clamped homogeneous electric field (CHEF) technique and found to be different. Based on the above differences, the sea-snake Blastocystis was designated as Blastocystis lapemi sp. nov. PMID- 1757202 TI - Purification, quantification and mechanical hatching of eggs of the tapeworm, Hymenolepis diminuta. AB - Eggs of Hymenolepis diminuta were separated from host's feces using a combination of NaCl flotation, filtration through nylon monofilament screen cloths, and centrifugation. The resulting purified egg preparations (PEPs) were verified microscopically to be virtually free of contaminating debris. The relationship of absorbance (500 nm) of PEPs and 'number of eggs per unit volume' was linear, and such measurements provided a rapid, reproducible method for quantifying PEPs. The average wet and dry weights of individual eggs were 2.86 x 10(-7) and 0.458 x 10( 7) g, respectively. Eggs were mechanically hatched using a Dounce homogenizer with pestle 'A'. This technique caused no detectable damage to larvae and resulted in a high percentage of 'activated' (i.e. motile) larvae. PMID- 1757203 TI - Biochemical changes during the development of the miracidium of Gigantocotyle explanatum. AB - Analysis of various biochemical components during the development of the miracidium of G. explanatum showed marked changes, particularly in glycogen, protein and DNA levels. Though the total lipids remained more or less unchanged, alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids and phospholipid fractions were also recorded. Such changes could be intrinsically programmed for the cellular differentiation and organogenesis in larval amphistomes. PMID- 1757204 TI - Monoclonal antibody to a diagnostic Mr 24,000 antigen of Gnathostoma spinigerum. AB - Crude water extract (CA) was prepared from the advanced third-stage larvae of Gnathostoma spinigerum collected from livers of naturally infected eels. The extract was partially purified by chromatofocussing column chromatography and the fraction which contained specific antigen of G. spinigerum which was an Mr 24,000 glycoprotein was used to immunize five Balb/c mice for preparing immune splenocytes. Spleen cells were collected from one mouse which showed high serum titre by indirect enzyme-linked immunosorbent assay and contained specific antibody to the Mr 24,000 antigen as checked by Western blot analysis. The spleen cells were fused with myeloma Sp2/0 cells at a ratio of 10 spleen cells per one myeloma cell using polyethylene glycol 3350 as a fusogen. Thirteen out of 174 growing polyclones (7.5%) produced antibodies to the partially purified CA fraction. Among them, two polyclones produced antibody directed to the Mr 24,000 protein. These two polyclones were subjected to monocloning by limiting dilution and a monoclone GN6/24 which produced monoclonal antibody to the specific Mr 24,000 protein of G. spinigerum was obtained. PMID- 1757205 TI - Swimming in a sub-adult monogenean of the genus Entobdella. AB - Swimming in a sub-adult monogenean parasite is reported for the first time. When detached from the substrate, a specimen of an undescribed species of Entobdella from the ventral skin surface of the cow-tailed ray, Dasyatis sephen, was found to propel itself vigorously through the water, head-first, by rapid dorso-ventral body undulations travelling in an antero-posterior direction. These waves pass in the opposite direction to the slower breathing (?) undulations exhibited by the attached parasite. Benedeniella macrocolpa from another elasmobranch host and benedeniines from teleost fishes merely made uncoordinated wriggling movements when detached from the substrate. The possible function of swimming in monogeneans is discussed. PMID- 1757206 TI - Metalloproteinases in the larvae of Echinococcus granulosus. AB - Proteolytic activity in hydatid cyst fluid, cyst membranes and protoscoleces of E. granulosus was analyzed by electrophoresis in gelatin-containing polyacrylamide gels, including characterization with a set of protease inhibitors. All contained metalloproteinases in the range 60-120 kDa, with neutral/alkaline pH optima. Major activity was observed in hydatid fluid and the membranes (five bands) with both exhibiting similar electrophoretic patterns. The samples prepared from protoscoleces shared only some of these bands. PMID- 1757207 TI - The toxicity of adenosine analogues against Babesia bovis in vitro. AB - The toxicities of 20 analogues of deoxyadenosine or adenosine were tested in vitro against the intraerythrocytic parasite Babesia bovis. IC37 values (the concentration of compound required to reduce cell survival to 37%) were determined for each compound. Tubercidin (7-deaza-adenosine), 2-bromo-adenosine, 8-bromo-3-ribosyl adenine and 6-phenylamino-deoxyadenosine were shown to be the most toxic towards B. bovis. Comparison of the toxicity results for these compounds in B. bovis with those in human melanoma cell lines indicated a differential toxicity, in that many of the compounds were toxic towards B. bovis but were relatively non-toxic towards human melanoma cell lines and vice versa. These results suggest that the mechanism of toxicity of the deoxyadenosine and adenosine analogues, whose normal metabolism involves transport, metabolism and incorporation into nucleic acids, may vary significantly between B. bovis and mammalian cells, allowing such drugs to be considered for parasite chemotherapy. PMID- 1757208 TI - Trypanosoma cf. carassii: the combination of malic enzyme patterns supports the theory of diploidy in trypanosomes. AB - Electrophoretic analysis of Trypanosoma cf. carassii strains from cyprinid fish revealed three basic types of enzyme patterns of malic enzyme (ME) in forms from culture. Two enzyme patterns were one-banded and differed only slightly in electrophoretic mobility. The third pattern consisted of three bands, the two marginals corresponding to respective bands of one-banded patterns and the third located in the middle. ME is thought to be dimeric in trypanosomes and therefore the triple-banded pattern may be regarded as the hybrid from combination of the former two. This fact supports the concept of diploidy in fish trypanosomes. PMID- 1757209 TI - The stability of the fetal oxygen environment. PMID- 1757210 TI - Pancreatic insulinoma localised by intra-operative ultrasound. PMID- 1757211 TI - A role for a non-androgenic anovulant in the management of hirsutism. AB - Sixty-nine patients who had Ferriman/Gallwey hirsutism scores (FG) of greater than or equal to 8 were treated with Diane, an anovulant containing cyproterone acetate, 2 mg, an anti-androgenic progesterone and ethinyl oestradiol, 5.0 micrograms. Twenty-one of these had been previously treated with dexamethasone (DEX) and did not respond, i.e. FG greater than 50% of pre-treatment value. Prior to Diane treatment, plasma total testosterone (T) values, 1.4 +/- 0.5 nmol/l, mean +/- S.D., were similar to those in 43 normal women, 1.23 +/- 0.3 nmol/l, as were plasma androstenedione levels, 6.8 +/- 2.5 and 6.0 +/- 1.7 nmol/l respectively. However, plasma sex hormone-binding globulin (SHBG) values were suppressed being 36.2 +/- 16 nmol/l in hirsute women and 45.8 +/- 15 nmol/l in normal women, p less than 0.01. The T/SHBG ratio, an index of free testosterone, was elevated in hirsute women, 4.8 +/- 4.1, compared to values in normal women, 2.9 +/- 1.0, p less than 0.001. Following Diane therapy (2-24 months), 73% of patients responded clinically. There was no change in T, but SHBG was increased to 181 +/- 54 nmol/l, p less than 0.001 and T/SHBG was decreased markedly to 0.9 +/- 0.4, p less than 0.001. Androstenedione fell also to 4.8 +/- 1.7 nmol/l, p less than 0.001. The clinical and hormone response to Diane was similar in both DEX-resistant and previously untreated groups. We conclude that Diane is an effective agent in the treatment of hirsutism while it avoids the adverse effects of androgenic progesterone and of high dose cyproterone acetate therapy. PMID- 1757212 TI - Experience with a juvenile rheumatology clinic. AB - A dedicated monthly clinic for children with rheumatic diseases was established in order to cater for the increasing number of referrals to a rheumatology department for assessment and management. The clinic was staffed by a consultant rheumatologist, registrar, nurse, physiotherapist and occupational therapist. Seventy-four children, 44 girls and 30 boys, were assessed during the first 32 months. The mean age at referral was 10 years (range 2-15). Thirty-three had juvenile chronic arthritis. Other disease categories included dermatomyositis, systemic lupus erythematosus and reactive arthritis. Twenty-eight children were referred by general practitioners and 26 by paediatricians. Hospital admission was required by 24. These observations suggest the need in Ireland for a coordinated service for children with rheumatic diseases. PMID- 1757213 TI - Immunosuppressive therapy in autoimmune disease--a review. PMID- 1757214 TI - Home environmental temperatures in an Irish infant population. AB - In this study the ambient temperature in which thirty-three Irish infants, within six weeks of birth, were nursed was documented. The study was conducted from October to March and a total of 1,250 individual room temperatures were recorded with a mean of 19.3 degrees C and a range of 8 degrees C, to 28 degrees C. The highest ambient temperature occurred from 1800 to 2100 hours and the lowest from midnight to 0300 hours. There was no central heating in 60% of the homes in this study. Comparing the various methods of home heating we found that houses with a coal fire and back boiler had the greatest range of temperatures recorded (from 10 degrees C to 23.5 degrees C) and also the lowest mean temperature recorded (17.14 degrees C). There was little relationship found between the ambient temperature and the amount of clothing and bedding used and some infants were heavily clothed despite a high ambient temperature. The purpose of this paper is to provide background data on which to base future studies examining the effects of varying ambient temperatures and amounts of clothing on an infant's physiological homeostasis. PMID- 1757215 TI - Effects of monosialoganglioside GM1 in experimental models of ischemic brain damage. AB - Systemic administration of monosialoganglioside GM1 is efficacious in reducing excitatory amino acid (EAA)-related neurotoxicity in vivo following intracerebroventricular injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Five days later, NMDA-treated animals showed extensive brain damage which was accompanied by significant decreases in brain weight, choline acetyltransferase activity and 3H-ouabain binding. All these neurotoxic effects were significantly reduced with ganglioside treatment. Since excessive activation of EAAS is implicated in hypoxic-ischemic brain damage, these results favor the hypothesis that a similar effect is involved in the ability of ganglioside to ameliorate outcome following cerebral ischemia. PMID- 1757216 TI - Neuropathological evaluation of brain damage in a rabbit model of focal cerebral ischaemia. AB - In the present paper we studied different methods for a qualitative and quantitative morphologic assessment of the focal brain damage in rabbits after occlusion of the middle cerebral artery with vaseline microspheres. The study of the early brain ischaemic damage (4 to 12 hours after embolisation) was performed on serial coronal cryostat sections of hemispheres frozen in liquid nitrogen and processed for NADH enzyme-histochemical method. In the ischaemic area the necrotic cells were pale or negative after enzyme-histochemical reaction, but a quantitative assessment of the ischaemic area was approximative. The Evans blue method for the identification of the region of the edema at 24 hours after embolisation showed inconstant results. A reproducible method for a quantitative assessment of the ischaemic area up to the 24th hour after embolisation was proposed by Osborne and utilised in the present experimental conditions. The volumetric assessment of the ischaemic area was obtained after delineation of brain damage areas at 8 preselected coronal levels with a computerized automatic image analyzer and by integration of areas with the distance between each level. In treated animals, the measures of the volume of cerebral infarction were accurate and reproducible, and were suitable for neurophysiologic correlations. PMID- 1757217 TI - Evoked potentials monitoring of a cerebral focal ischemia model. AB - A model of cerebral ischemia by microsphere embolization in the rabbit was monitored with somatosensory evoked potentials by median nerve stimulation (SEPs) and by flash visual evoked potential (VEPs). The degree of SEP alterations paralleled the type of lesions (focal or multifocal ischemia or diffuse oedema). Alterations present at the first hour after ischemia were generally unchanged during the follow-up, which ended at the 24th hour. The prevalence of VEP alterations was low (only 16% in focal ischemia). These results are compared to EEG modifications performed in the same animals. PMID- 1757218 TI - Hemodilution and revascularization for early treatment of stroke: an experimental trial. AB - A new experimental trial to investigate the usefulness of early therapeutic measures in case of acute I.V.D. has been performed, on the basis of a previous already reported experience. A combined treatment consisting of hemodilution and revascularization starting 16 hours after the onset of cerebral ischemia was tested. The study was performed in a population of 20 New Zealand male rabbits in which an acute cerebral ischemia was achieved by means of extracranial ligation of both common carotid artery and of one vertebral artery. The animals were divided into two groups. 1st group: no treatment; 2nd group: revascularization + hemodilution. Better results were observed in treated group considering either CBF rates or histological changes. PMID- 1757219 TI - Vascular microsurgical anastomosis in hypercholesterolemic rats: an experimental study. AB - Patency of vascular microanastomosis was examined in aging (6 months) and hypercholesterolemic rats, reproducing conditions similar to those occurring in human pathology. Results have been compared with those achieved in normocholesterolemic, younger (aging less than 8 weeks) rats. PMID- 1757220 TI - Arterial micro-prosthesis with polytetrafluoroethylene in rabbits. AB - An experimental trial has been realized in rabbits interposing a polytetra fluoroethylene (PTFE) graft through the left carotid artery. Patency has been compared to one obtained by utilization of vein grafts in identical conditions. PMID- 1757221 TI - Transient cerebral ischemia in the rat: a study by nuclear magnetic resonance spectroscopy. AB - The energy state and the levels of metabolites involved in the phospholipid turnover during and following a transient cerebral ischemia have been evaluated with the aids of 31P and 1H nuclear magnetic resonance spectroscopy. Ischemia was induced by electrocoagulation of vertebral arteries in combination with transient occlusion of both common carotid arteries. After 10-min ischemia, the brain energy charge and the levels of high-energy phosphates were reduced, whereas lactic acid levels had undergone an 8-fold increase. Sixty minutes after cerebral blood flow recovery, brain energy charge and levels of high-energy phosphates returned to basal values, whereas lactic acid levels remained persistingly elevated; an increase in phosphocreatine was also observed. At this same time, glycerolphosphorylcholine levels were found to be significantly reduced. PMID- 1757222 TI - The brain-heart syndrome: remarks on early ecgraphic changes following focal cerebral ischemia in healthy and in experimentally hyperdyslipidemic rabbits. AB - Early cardiac effects of focal cerebral ischemia in two groups of rabbit, one of which made hyperdyslipidemic with an atherogenic diet, were detected in several experiments. In the group of 62 animals fed on a standard diet, primary CVT alterations and arrhythmias occurred in 4 rabbits (6.4%), in the group of 15 animals fed on an atherogenic diet the same cardiac alterations occurred in 6 rabbits (40%). A marked statistically significant prevalence of ECGraphic changes was observed in hyperdyslipidemic group. These results and the data coming out of other experiments and literature suggest that the pathogenesis of the "cerebro cardiac syndrome" is linked to several biohumoral alterations occurring after the stroke. If these events affect functionally damaged endothelia, or occur in the presence of atherosclerotic plaques, cardiac alterations occurring after the stroke are greater than cardiac alterations observed in the same condition when coronary are intact or little damaged. PMID- 1757223 TI - A new model of focal brain ischemia based on the intracerebral injection of endothelin-1. AB - Endothelin-1 and its receptors are widely distributed in the brain of rodents and humans. In view of its potent and long-lasting vasoconstrictor activity, a role of endothelin-1 has been proposed in brain ischemia. In the present paper, the local injection of endothelin-1 was utilized to induce ischemia in rat striatum. An evaluation of the rostrocaudal extension of the lesion is reported. By using intracerebral microdialysis, a marked increase of lactate and dopamine, but not glutamate, was observed in this region upon endothelin-1 administration. Moreover, preliminary data reported show a protective effect of ganglioside treatment on endothelin-1 lesion of rat striatum. The characteristics of the present model of brain ischemia are discussed in comparison with well characterized models, such as the Pulsinelli's four vessel occlusion and the middle cerebral artery occlusion. PMID- 1757224 TI - Endothelin: an endothelium-derived vasoactive peptide and its possible role in the pathogenesis of cerebral vasospasm. AB - The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline injected controls. Endothelin elicited strong concentration-dependent contraction of rat basilar artery segments. The response was slow in onset and long lasting. The endothelin-induced contraction was much stronger in the SAH compared to control animals. Our findings suggest a role of the peptide in the pathophysiology of cerebral vasospasm. PMID- 1757225 TI - Protective effect of cyproheptadine in a gerbil model of cerebral ischemia. AB - The efficacy of Cyproheptadine, a serotonin antagonist, in preventing the cerebral ischemic damage was tested on experimental model of transient global cerebral ischemia in Mongolian Gerbil. The semi-quantitative histological evaluation of the severity of ischemic damage showed a protective effect of Cyproheptadine, mainly in the anterior cortical areas. PMID- 1757226 TI - Changes in infratentorial blood flow following experimental cerebellar haemorrhage. A preliminary report. AB - The temporal progression of changes in blood flow within the hemispheric cerebellar cortex, following an experimental cerebellar ipsilateral haemorrhage, was investigated in rats by using the hydrogen clearance technique. Stereotactical injection of 50 microliters of fresh autologous blood into the paramedian white matter was found to produce an early drop of cerebellar blood flow, with subsequent rise toward higher values. An increase of the intracranial pressure only occurred at the time of injection of blood. Arterial blood gases, mean arterial blood pressure and blood glucose levels did not exhibit significant changes. Histochemical evaluations of glycogen phosphorylase showed a posthaemorrhagic pattern of enzyme depletion, consistent with the occurrence of an ischaemic damage in both the cerebellum and the brain stem. PMID- 1757227 TI - Bilateral carotid occlusion in normotensive rats: olds facts and new observations. AB - This work describes that prolonged mild cerebral ischemia may lead to either general or regional derangement of brain morphofunctional integrity. Normotensive adult Wistar rats were used. Under anesthesia with volatile agents or thiopental, the common carotid arteries were ligated permanently. In one group of animals local cerebral blood flow (1CBF) was measured two hours after carotid occlusion using the [14C]iodoantipyrine method. The other carotid-occluded animals were used for clinical rating and histological evaluation, which was performed two days to 4 weeks after surgical operation. The [14C]iodoantipyrine method showed widespread reduction in the cerebral circulation of carotid-occluded animals. Several hours after carotid occlusion, 40% of the animals showed dramatic neurological signs and died on the day of operation. In 35% of surviving animals, brain infarctions were observed in one and exceptionally two areas of the sensorimotor cortex, thalamus, hippocampus or cerebellum. The evolutionary sequence of the histopathological changes seems to date the induction of the infarcts to the early period of carotid occlusion. In conclusion, reduction of cerebral blood flow causes, in a high percentage of animals, various degrees of acute brain damage after an apparent symptom-free interval. PMID- 1757228 TI - Israeli medical lessons from the Gulf war: an overview. PMID- 1757229 TI - The Persian Gulf War: Israeli medical experience and perspectives. PMID- 1757230 TI - Medical aspects of the Iraqi missile attacks on Israel. AB - During the period 18 January-28 February 1991, a total of 39 Iraqi modified Scud missiles landed in Israel, most of them in the densely populated Tel Aviv area. There were 23 missile attack alerts. These attacks caused 1,059 cases of injury; there were two deaths and 232 patients were admitted to emergency rooms for injuries directly related to the explosions, only one of which was severe. A survey among 91 of the injured showed that 46.6% of the wounds were caused by glass splinters, 31.1% were blunt contusions, and 22.2% were acute psychological reactions. No case of blast injury was reported. Inappropriate injection of atropine was reported in 230 cases. Acute anxiety was the reason for admission of 544 patients to emergency rooms. Another 40 patients sustained various traumas while rushing to the sealed room. The relatively low number of injured people is striking in view of the density of population in the areas hit. Various explanations are discussed. PMID- 1757231 TI - Eighty years of the threat and use of chemical warfare: the medical organizational challenge. AB - The threat of using chemical warfare (CW) by countries ruled by dictators and totalitarian governments still exists despite the Geneva Convention of 1925 that prohibited the use of CW. This situation forces nations and their armed forces to be in a state of preparedness in the event of a CW attack. A CW attack on an unprotected civilian population in a dense urban area can cause numerous casualities and become a mass disaster. However, this danger may be significantly reduced by: a) providing collective and individual protective measures, b) training the population in the use of protective measures, and c) early warning to provide sufficient lead time to use the various components of protection. Coping with a nonconventional warfare threat requires an innovative approach in the organization of the health care delivery system so as to maximize the number of survivors. The fact that the population is protected may deter the enemy from using CW since the potential destructive impact of CW is neutralized or at least reduced. PMID- 1757232 TI - Civilian-military health services contingency program for a mass casualty situation and wartime in Israel. AB - The Israeli civilian-military health services contingency program for mass and wartime casualties has more than four decades of experience. The contingency program includes key civilian and military organizations that are involved in the planning, policy making and delivery of health care and support services to the wounded. During the Persian Gulf war the unified civilian and military command- the supreme hospitalization authority--implemented a national hospital and emergency medical services preparedness system designed to treat the victims of chemical warfare attacks. PMID- 1757233 TI - Outline of hospital organization for a chemical warfare attack. AB - A plan for hospital organization in the event of chemical warfare is described. The basic principles are: a) isolation of the hospital receiving the casualties, b) several levels of triage, and c) treatment according to simple therapeutic protocols using appropriate treatment sites. Triage is based upon walking feasibility, respiratory status, age, and additional conventional injuries. The nurse's diagnostic and treatment authority is extended. Auxiliary staff (numbering hundreds of people) are needed for decontamination, stretcher bearing, artificial ventilation, etc. A nation-wide educational program on the prevention, decontamination and treatment of chemical warfare casualties is conducted in Israeli hospitals and drills are exercised frequently. This scheme is suitable for nerve gas poisoning, but can be easily modified for other chemical agents. PMID- 1757234 TI - Combined chemical and conventional injuries--pathophysiological, diagnostic and therapeutic aspects. AB - Chemical warfare (CW) agents may cause both conventional and chemical injuries. The effects of the two types of injuries may be reciprocal, leading to difficulties in assessing and treating such patients. Several aspects of the combined injury are discussed: increased exposure to CW agents following conventional trauma, owing to skin laceration or inability to use a gas mask (head, face or chest trauma); pathophysiological interactions between the two types of injuries; protection of medical personnel against CW intoxication; treatment limitations of personnel caused by their CW protection gear, when treating patients requiring urgent decontamination; and the influence of conventional trauma on the management of CW casualties. The Israel Defense Forces' recommendations for the treatment of combined injuries in a contaminated area include: a) airway maintenance, b) securing breathing and ventilation, c) circulation and hemorrhage control, d) antidote administration, e) decontamination with fuller's earth, f) dressing the wound, and g) evacuation to a noncontaminated area. PMID- 1757235 TI - Mortality in Israel during the Persian Gulf war--initial observations. AB - During the 6-week-long 1991 Persian Gulf war, in which the civilian population was subjected to 18 separate missile attacks and the constant threat of nonconventional warfare, crude mortality rates in Israel were no higher than in the previous decade. Although the results are preliminary and need to undergo more sophisticated epidemiologic analysis, it appears that our population was able to tolerate the subacute period of psychological stress without excess mortality. PMID- 1757236 TI - Fewer injuries but more deaths from road accidents during the Persian Gulf war. AB - During the period 13 January to 28 February 1991, traffic accidents were the cause of death in 45 persons (31 vehicle and cycle occupants and 14 pedestrians) and of injuries in 2,769 persons (2,309 occupants and 460 pedestrians) in Israel. During the same period 18 persons (13 occupants and 5 pedestrians) died as the result of traffic accidents in the Territories (Judea/Samaria and the Gaza Strip). The decline in the number of injuries among occupants and pedestrians was offset by the increase in the case fatality rate (CFR), particularly among occupants, compared with: a) the previous 6 months, b) the same period of the previous year, a) the ratio of the reduced CFR in January-February in relation to the previous 6 months, and d) the CFR predicted by the declining CFR in January February of the previous 5 years. Compared with 1990, in 1991 during the Persian Gulf war the roads were less crowded and crash occurrences were less frequent, but travel speeds, crash impacts and kinetic energy delivered to victims (especially occupants on inter-urban roads) were greater. Daytime running lights on two-lane roads; temporary lower speed limits; the use of new roadside monitoring methods for detecting and deterring speeding, tailgating and speedgating; the collection of tachygraph data; and implementation of the requirement for a rear seat belt are measures suggested to have been effective in swiftly reducing the toll of dead and injured, not only during but after the Gulf war as well. PMID- 1757237 TI - Principles of respiratory protection. AB - This review describes the various types of respiratory protective devices used in Israel during the Persian Gulf war, and summarizes the relevant physiological concepts of respiratory protection. Physiological principles of modern devices with powered air supply are discussed in detail. Our experience may be useful in the evaluation of new respirators and in finding solutions for problematic subpopulations. PMID- 1757238 TI - Physiological assessment of the passive children's hood. AB - The physiological effect of the "passive children's hood" (PCH) was studied in 24 children: 8 toddlers (3-4.5 years old), 8 pre-school pupils (4.5-6 years) and 8 first- and second-grade pupils (6-8 years). This device consists of a children's gas mask and a transparent PVC (polyvinyl chloride plastic) covering (hood). Inspiratory CO2 and O2 (FiCO2 and FiO2, respectively), temperature and humidity were monitored at 10-min intervals while the children were occupied with sedentary activities (playing and watching TV) in a sealed room. Ambient temperature and relative humidity were approximately 27 degrees C and 75% respectively. In the PCH space the temperature was 2 degrees C higher and humidity was near saturation at the end of exposure. FiCO2 in 12 children exceeded 2%, which is the upper acceptable limit according to industrial standards. In four of them FiCO2 was greater than 4% and FiO2 less than 16%. Twenty-two children tolerated the PCH for 92 +/- 35 min (range 24-133 min) with no physiological complications. A significant correlation was found between childrens' age and tolerance time (r = 0.47, P less than 0.025). We conclude that children whose masks are not well adjusted may be exposed to rebreathing CO2 enriched air. PMID- 1757239 TI - The incubator as a chemical warfare protective device in neonatal intensive care units. AB - During the Persian Gulf war chemical warfare (CW) protective devices were distributed to the entire population of Israel. Neonates were to be placed in a protective infant carrier (PIC) or an improved PIC ("active PIC") to which filtered air was actively introduced by a blower. The specific needs of low birthweight babies hospitalized in intensive care units and treated in incubators were not adequately addressed. Transfer to a PIC meant disconnecting the infants from life-supporting systems and monitoring devices and exposing them to changes in ambient temperature. To overcome this difficulty the original incubator was used as a CW protective device. Its ports were sealed and low-grade positive pressure was created. This avoided transfer of the neonates from their controlled environment, reduced physiological stress, and improved medical supervision. PMID- 1757240 TI - An argument for equipping civilian hospitals with a multiple respirator system for a chemical warfare mass casualty situation. AB - During the Persian Gulf war, the entire Israeli population was under the threat of chemical missiles. One of the main effects of chemical agents (e.g., organophosphorus) is respiratory distress, which requires treatment with mechanical ventilation and oxygen enrichment. In the event of a chemical missile attack, the civilian hospitals may enter a state of insufficiency for treating such victims due to the limited amount of equipment, staff and oxygen/air sources. A possible technological solution is a multiple respirator system (MRS) with a multiple oxygen enrichment system designed for use in the battlefield. The advantages of these technologies in the civilian hospital setting during a chemical mass casualty situation are: (a) rapid deployment, (b) high transportability, (c) capability of operation in any location, (d) modularity, and (e) less medical staff for operation. Two types of MRS are described and issues concerning their selection are discussed. The authorities responsible for national health policy may wish to adopt and incorporate these technologies into their hospital and emergency services preparedness system. PMID- 1757241 TI - Survey of symptoms following intake of pyridostigmine during the Persian Gulf war. AB - Pyridostigmine bromide, a reversible inhibitor of acetylcholinesterase (AChE), is effectively used as a pre-treatment to organophosphate intoxication. Previous studies have shown that an oral dose of 30 mg twice a day produces a sufficient inhibition of the enzyme activity (20-40%) without causing any significant adverse effect. During the Persian Gulf war pyridostigmine was taken for the first time under a chemical warfare threat. We searched for symptoms and complaints that may be related to the medication. Our survey included 213 soldiers who completed a questionnaire regarding possible symptoms and their severity. AChE inhibition level was compared between groups of soldiers with and without complaints. The most frequent symptoms were nonspecific and included dry mouth, general malaise, fatigue and weakness. Typical effects, such as nausea, abdominal pain, frequent urination and rhinorrhea, were infrequent. The severity of the symptoms was generally mild. The symptoms appeared around 1.6 h after taking the medication and recurred after each intake. No correlation was found between levels of cholinesterase and type or severity of complaints. Anxiety, which accompanies wartime, may have contributed to the appearance of significant symptoms. Further investigations concerning the effects of pyridostigmine ingestion under stressful conditions are warranted. PMID- 1757242 TI - Acute pyridostigmine overdose: a report of nine cases. AB - Pyridostigmine is known as a pre-treatment drug against intoxication with organophosphorus nerve agents. During the Persian Gulf war, we encountered a cluster of nine cases of pyridostigmine self-poisoning, of which three presented with mixed drug poisoning. The clinical and laboratory features of pyridostigmine toxicity are presented. Doses ranged between 390 and 900 mg. Pyridostigmine ingestion resulted in mild to moderate cholinergic symptoms such as abdominal cramps, diarrhea, emesis, nausea, hypersalivation, urinary incontinence, fasciculations, muscle weakness and blurred vision. No central nervous system manifestations were evident. The symptoms developed within several minutes and lasted up to 24 h. All patients underwent gastric emptying followed by administration of activated charcoal. Atropine (1-8 mg) was required in only three patients. Measurement of serum cholinesterase inhibition was found to be a reliable and sensitive diagnostic tool in pyridostigmine poisoning. No clear correlation was found between the extent of cholinesterase inhibition and the incidence or severity of the cholinergic signs. The clinical recovery was faster than the spontaneous recovery of the enzyme. Pyridostigmine intoxication is self limited and well tolerated by young healthy adults. PMID- 1757243 TI - The effect of pyridostigmine on respiratory function in healthy and asthmatic volunteers. AB - Respiratory function was evaluated in 12 healthy and 13 asthmatic volunteers following a single oral dose of pyridostigmine in a double-blind, placebo controlled cross-over study. Respiratory function tests were performed at rest and after submaximal exercise at the time corresponding to the expected peak cholinesterase inhibition by pyridostigmine. A single dose of 60 mg pyridostigmine given to nonasthmatic subjects led to a decrease of 28.4% in cholinesterase activity when compared to the baseline and a statistically (but not physiologically) significant decrease in FEV1 (forced expiratory volume in 1 sec) both at rest (P less than 0.015) and after exercise (P less than 0.05). This effect showed a strong correlation to the degree of cholinesterase inhibition (r = -0.936, P less than 0.0001). According to these findings, a smaller dose of pyridostigmine (30 mg) was given to subjects with mild bronchial asthma. At that dose, pyridostigmine resulted in a similar inhibition of cholinesterase activity to a mean of 76.7% of the baseline. A significant decrease in the pulse rate was also found (P less than 0.005). However, no changes in respiratory function were observed when compared with the effects of placebo. The effect of post-exertion atropine inhalation on respiratory function was also unchanged with pyridostigmine at that dose. We conclude that, in general, at this dose pyridostigmine is a safe drug for asthmatics; however, the distribution of individual results in this group cannot preclude the existence of a subpopulation of asthmatic patients who are more vulnerable to the effects of pyridostigmine. PMID- 1757244 TI - Hyperbaric oxygen treatment for carbon monoxide intoxication acquired in the sealed room during the Persian Gulf war. AB - During the recent Persian Gulf war, the civilian population in Israel was frequently instructed to stay in sealed rooms in preparation for a possible chemical missile attack. The war broke out in mid-winter, and in many instances it was necessary to heat the rooms. The use of open fires or malfunctioning heating appliances inside sealed rooms could create ideal conditions for carbon monoxide (CO) poisoning. Six patients with CO intoxication resulting from confinement inside sealed rooms were referred for hyperbaric oxygen (HBO) treatment. Indications for HBO therapy were loss of consciousness and metabolic acidosis. The treatment protocol consisted of 90-min exposure to 100% oxygen at 2.5 atmospheres absolute (ATA), with repeated exposures when required. All patients made a full recovery. The risk of CO poisoning should be taken into consideration and should determine the selection of heating devices for future use in similar circumstances. PMID- 1757245 TI - Israeli psychological casualties of the Persian Gulf war: characteristics, therapy, and selected issues. AB - The Persian Gulf war in 1991 presented Israel with its first experience of a threat of chemical attack on the home front. Ground-to-ground missiles were aimed directly at civilian populations, threatening death and destruction over a period of several weeks. Uncertainty as to time, place, and nature of the missile attacks affected the civilian population psychologically. The psychological responses of the population were the result of the continuous nature of the emergency which affected the entire population, and the destruction, injury, and displacement which affected those who were the targets of the attacks. The primary psychological effects of the emergency were investigated in several ways: surveys of samples of civilian and rear-echelon military populations, studies of the military personnel who asked for ambulatory psychological treatment as a result of the war, and studies of the specific populations that bore the brunt of the actual physical attacks were conducted. These studies show a high level of distress in the samples, with considerable differentiation between the populations. Levels of functioning generally remained intact even among the displaced or injured. Interventions were based on experience gained in the treatment of combat stress reaction. The issues of evacuation of psychological casualties to hospitals, psychiatric aspects of chemical attacks, and secondary traumatization of therapeutic and other staff are emphasized. PMID- 1757246 TI - Anxiety-related somatic reactions during missile attacks. AB - During the Persian Gulf war the Israeli civilian population was the target of missile attacks that could have carried poison gas warheads. During the attacks all civilians were ordered to wear gas masks and move into sealed rooms. Four telephone surveys studied the somatic reactions to this anxiety-arousing situation. The percent of subjects reporting the somatic reactions declined from 38% after the first attack to 20% 12 days later. Somatic reactions were more prevalent among females than males, and among those who completed elementary school only compared to those with an academic education. A complex pattern of relationships between expectancies about chemical warfare attacks and somatic reactions is discussed. PMID- 1757247 TI - Sleeping under the threat of the Scud: war-related environmental insomnia. AB - The influence of the Scud missile attacks during the Persian Gulf war on the sleep of the Israeli population is described. Our study group comprised a random sample of 200 people (mean age 41.13 +/- 15.32) who were contacted by telephone during the third week of the war and interviewed about their sleep. Overall, 28% of the entire sample complained about sleep: 10% complained about mid-sleep awakenings, 4.5% on difficulties falling asleep, and 13.5% about the combination of the two. People living in the Tel Aviv and Haifa areas complained significantly more than those in the rest of the country. Women complained significantly more than men, and people with lower education complained significantly more than people with higher education. Only 3% of the sample reported using sleeping pills. During the war actigraphic sleep recordings in 19 adults living in the Tel Aviv and Haifa areas did not reveal any measurable decrease in sleep quality in comparison with pre-war recordings. Possible explanations for the discrepancy between the subjective and objective assessments are discussed. PMID- 1757248 TI - In the shadow of the Gulf war: psychological distress, social support and coping among Israeli soldiers in a high risk area. AB - This study assessed the sense of safety, psychiatric symptomatology, coping and sources of support among eight groups of soldiers stationed in the region at highest risk for missile attacks during the Persian Gulf war. The sample consisted of 659 regular, reserve, and career soldiers, both male and female. Findings show that elevated levels of distress were associated with a high level of perceived threat, a low level of perceived self-efficacy, a low level of trust in army authorities, and a low level of support from the social network, particularly from commanding officers. Practical implications are discussed. PMID- 1757249 TI - Community coordination and information centers during the Persian Gulf war. AB - During a time of crisis, community information centers provide valuable data to the public and help to avoid confusion and misinformation. During the Persian Gulf war, Kupat Holim (sick fund of the General Federation of Labor) established a national casualty information center in Tel Aviv as well as numerous coordination and information centers throughout the country, which included district, geriatric, psychological and emergency centers, as well as one for new immigrants. These centers had not been planned in advance, but because of the obvious need, they were established in the few months prior to the outbreak of the war and during the war itself. The locations of the centers were publicized through the media. In this article we report on the different centers and their activities, and additional community measures are described. The plan of establishing information centers throughout the country proved itself a vital necessity and will be incorporated in future Kupat Holim plans for war or any other emergency situation. PMID- 1757250 TI - Role of the Tel Aviv-Jaffa municipal workers in the treatment of survivors of missile blasts. AB - Of the nine missiles that landed on the city of Tel Aviv-Jaffa during the Persian Gulf war, three fell in heavily populated areas. As a result 192 people were sent to hospital and 1,663 (520 families) were left homeless. These were seen and evaluated near the site of the blast by a municipal multidisciplinary team and then sent to one of 15 hotels in and outside the city. There they were treated for acute post-traumatic stress disorder by a municipal health care team (general physicians, nurses, social workers and psychologists) and by psychiatrists from a local sick fund. Many acute and chronic medical problems, including attempted suicide, were also encountered. Community outreach programs aimed at high risk groups and several telephone counselling services were also instituted. We believe that it is crucial to train and provide a multidisciplinary team for handling the survivors of major disasters. PMID- 1757251 TI - Willingness of staff to report to their hospital duties following an unconventional missile attack: a state-wide survey. AB - Adequate staffing of hospitals during a prolonged, potentially unconventional war is a key component in the disaster plan of institutions. In an attempt to determine policy regarding hospital staffing, a state-wide survey was conducted in Israel among hospital personnel during the recent Persian Gulf war. This survey aimed to explore the willingness of staff to report to their duties (WTR) following an unconventional missile attack described in a hypothetical scenario. Of the 2,650 questionnaires distributed among all categories of staff in 10 hospitals (42%) across the country, 51% were returned. Overall, 42% of the responding staff were WTR under the presented scenario. However, WTR would increase to 86% if safety measures were provided. Males, personnel with headquarter duty of hospital site managers, and parents of children older than 14 years of age, were the most WTR. The finding of extensive interhospital variation in WTR indicates the need for evaluating WTR on an institutional basis when establishing both the hospital and the regional disaster plan. Data are presented on the extent of WTR, the factors inhibiting WTR, and possible measures to improve WTR. PMID- 1757252 TI - [Immunoglobulin therapy in IgE-mediated allergic diseases]. PMID- 1757253 TI - [The significance of protein C deficiency in dermatology]. AB - The protein C system is a physiological inhibitor of coagulation and is important for the regulation of hemostasis. Protein C deficiencies can be inherited or acquired, and they lead to enhanced thrombophilia. A number of clinical entities that are also of interest to dermatologists have been related to protein C deficiency. Inherited protein C deficiency can become manifest in various ways, e.g. as purpura fulminans neonatalis, as recurrent episodes of thrombosis and as coumarin necrosis. Acquired protein C deficiency can be observed in the course of purpura fulminans, disseminated intravascular coagulation, hepatic failure or in the presence of antiphospholipid antibodies. The clinical features, the possible pathogenesis and the therapy of these manifestations are briefly discussed. PMID- 1757254 TI - [Chronic actinic dermatitis. Concept and case examples]. AB - Two women patients with chronic eczematous dermatitis, who also developed extremely severe, persistent photosensitivity during a course of 10 and over 40 years, are presented. Both patients had an atopic history with positive immediate skin reactions. Patch and photopatch tests revealed sensitization to several contact allergens, and in one case also a photocontact allergy. The action spectrum of the photosensitivity was confined to UV-B; it was possible to provoke eczematous skin reactions with doses smaller than 1 mJ/cm2 UV-B. Both patients were successfully treated with PUVA therapy. These case reports demonstrate the difficulty of nosological classification of chronic eczematous photosensitive dermatoses under the traditional terms persistent light reaction, photosensitive eczema, photosensitivity dermatitis, and actinic reticuloid. Chronic actinic dermatitis is defined clinically by chronic dermatitis on skin exposed to sun, histologically by spongiotic dermatitis, and photobiologically by experimental provocation of spongiotic dermatitis with UV-B and often also longer wavelengths in the absence of a photoallergen. Chronic actinic dermatitis should be used as a general term in addition to the more specific terms listed above. PMID- 1757255 TI - [Isolated pemphigus vulgaris of the mouth mucosa--pemphigus test: diagnostic confirmation using direct immunofluorescence study of normal skin]. AB - The diagnosis of oral pemphigus vulgaris (PV) without concomitant cutaneous manifestations is often complicated by difficulties in obtaining a biopsy specimen allowing histological examination and direct immunofluorescence (IF) microscopy. In this clinical study five of our patients with oral PV were investigated: biopsies were taken both from lesional oral mucous membranes and from unaffected gluteal skin for IF analysis. Identical IF results, with intercellular epidermal deposition of IgG in all and of C3 in two of the five cases, were obtained in lesional and nonlesional biopsies. Therefore, it is concluded that with current IF techniques examination of the normal skin is sufficient for the diagnosis of oral PV; thus, the often painful and difficult removal of biopsy specimens from within the affected oral cavity can be avoided. Further studies are needed to confirm the sensitivity of this method. PMID- 1757256 TI - [Eccrine angiomatous nevus]. AB - A case of eccrine angiomatous nevus in a 46-year-old woman is described. The histological examination revealed convolutions of eccrine sweat glands with no major structural abnormalities, and a closely related angiomatous component. Two components of this tumour are of special interest: the bone formation and a medium-sized artery with pathologic wall structure. PMID- 1757257 TI - [Oligosymptomatic Bourneville-Pringle tuberous sclerosis of the brain with giant cell astrocytoma]. AB - We report on a 9-year-old boy who developed subependymal giant-cell astrocytoma associated with tuberous sclerosis. Apart from a few hypopigmented skin patches, the boy's clinical picture was completely unremarkable until the onset of diplopia and vertigo reflecting increased intracranial pressure. Magnetic resonance imaging of the brain revealed subcortical hamartomas in addition to the intraventricular tumour. Seizures and mental retardation were absent. The boy's mother had suffered from seizures during childhood and presented with typical skin lesions. The importance of thorough examination and regular follow-up even in patients with oligosymptomatic variants of tuberous sclerosis is emphasized. PMID- 1757258 TI - [Pomade crust of the scalp simulating cornu cutaneum]. AB - A 63-year-old woman with a history of exaggerated use of topical skin care products of post-traumatic scarring alopecia presented with a monstrous cutaneous horn-like pomade crust of the scalp hidden beneath a wig. The crust consisted of corneocytes and bacterial debris. Pomade crusts have not been described previously in this localization. They are usually found in the inguinal or gluteal folds of infants, and occasionally in other body regions, e.g., on the face of adults. PMID- 1757259 TI - [Multiple sebaceous gland hyperplasias in X chromosome hypohidrotic ectodermal dysplasia]. AB - We report on a 46-year-old man with X-linked hypohidrotic ectodermal dysplasia, who presented with large skin areas covered with aggregated sebaceous gland papules on the face and neck. This is rare, but has been observed in very similar form in association with this disorder in a not insubstantial proportion of cases. PMID- 1757260 TI - [Tinea corporis caused by Microsporum gypseum]. AB - Human infections due to microsporum gypseum are rare. We report on a female patient who had tinea corporis caused by M. gypseum after a cutaneous wound. The numerous lesions located on the borders of the wound had an eczematous appearance. PMID- 1757261 TI - [Methotrexate--indications and adverse effects]. PMID- 1757262 TI - [Limits of hyposensitization in bronchial asthma]. PMID- 1757263 TI - [14th Annual Congress of the Society of Surgical and Oncologic Dermatology 10-12 May 1991 in Wurzburg]. PMID- 1757264 TI - [First International Symposium for Andrology in Graz 10-11 May 1991]. PMID- 1757265 TI - Etiology of drinking and driving among adolescents: implications for primary prevention. AB - A prospective study was conducted to investigate what factors are predictive of self-reported drinking and driving (DD) among adolescents. The study employs a theoretical framework taken from Problem Behavior Theory; environmental, personality, and behavioral factors are explored for their predictability of DD. A cohort of 1482 high school students completed a written survey in spring of 1986 and again in fall of 1986. The findings confirm that Problem Behavior Theory provides a useful theoretical framework with which to identify etiological factors predictive of DD among adolescents. Identified personality, perceived environmental, behavioral, and demographic factors accounted for approximately 50% of the reported variance in DD at baseline. The same factors accounted for approximately 40% percent of the variance in follow-up DD and were predictive both among the students who did not drink and drive at baseline (incidence cases), and among those students who did drink and drive at baseline (continuation versus discontinuation of the behavior). Based on these etiological data, we recommend that school-based, peer-led educational prevention programs be designed to reach young adolescents prior to the age at which a driver's license is obtained. We further recommend that the programs be broad-based and consider DD within the larger context of drinking and driving related behaviors and traffic safety in general. PMID- 1757266 TI - Development of a health education program to promote the self-management of cystic fibrosis. AB - The creative challenge of health education for chronic illnesses is the translation of theory-based intervention methods into practical strategies that can be organized into a logical series of learning activities to influence changes in environmental, cognitive, or behavioral factors. A case example describing the development and implementation of a comprehensive health-education intervention for the self-management of cystic fibrosis (CF) is presented. The design of intervention strategies began with an assessment of the educational needs for self-management of CF, followed by specification and validation of particular self-management behaviors. Behavioral and learning objectives then were formulated for each of the self-management behaviors. Constructs from social learning theory considered to be important influences on specified self management behaviors in CF were identified. Taking into consideration the learning needs of the target population and the practical constraints of the system for providing health care, various intervention methods then were devised based on social learning theory. Lastly, the intervention methods chosen were translated into strategies organized into a series of practical learning activities for CF patients and their families. The process described here should prove useful to others who are planning and developing comprehensive health education programs for self-management of chronic illnesses. PMID- 1757267 TI - Psychosocial factors and enrollment in a televised smoking cessation program. AB - Registrants for a smoking cessation program on the evening television news in the Chicago metropolitan area were compared with other smokers in the population to identify psychosocial factors that distinguished registrants. Telephone interviews were conducted before the intervention with random samples of 641 registrants and 2,398 smokers who regularly viewed the evening news. A nested series of three contrasts compared registrants with (1) smokers who regularly viewed the evening television news on any channel, (2) smokers who were regular viewers of the evening news on the intervention channel, and (3) smokers who were regular viewers of the evening news on the intervention channel and were planning to quit smoking. Registration was associated with a smoker's cognitive appraisal of the quitting process, with registrants distinguished by (1) recognition of a need to act (perceived severity of and susceptibility to lung cancer), (2) high outcome expectancies for quitting as an effective means for health promotion, (3) realistic expectations about the effort required to quit, (4) concern about the burden of lung cancer on significant others and related social influence factors, and (5) motivation to quit smoking. The findings suggest that the effectiveness of minimal-contact intervention programs may be enhanced by targeting smokers according to their psychosocial characteristics and by cognitively preparing smokers to attempt to quit. PMID- 1757268 TI - Using the health belief model to predict safer sex intentions among adolescents. AB - The purpose of this study was to use Health Belief Model (HBM) concepts to predict adolescents intentions to adopt safer sex behaviors. A stratified, random sampling technique was used to generate a sample of seventh-, ninth-, and eleventh-grade students representative of a southeastern state. A predictive model was constructed of the HBM variables. The model accounted for 43% of the variance in safer sex intentions among the seventh grade, 27% of the variance for the ninth grade and 17% of the variance for the eleventh grade. For the eleventh grade sample gender was the only significant predictor. The results of this study suggest that educational programs to promote safer sex intentions should focus on health related motivations among younger students. With older adolescents it may be more effective to expand education efforts to address factors directly relevant to their motivational schema and social environment. This study underscores the importance of using theory-based models in conducting health education research. PMID- 1757269 TI - Enhancing social support at the workplace: assessing the effects of the caregiver support program. AB - Although the health-enhancing effects of social support have been well documented, little is known about how to increase the flow of social support among network members. This article describes and evaluates the Caregiver Support Program, a worksite program that attempts to improve the quality of work relationships among house managers and direct care staff who work in group homes for the developmentally disabled. The program incorporates three strategies for increasing social support: (1) adding a new person or group of persons to the employee's social network, (2) enhancing existing relationships by improving the focal employee's skills for maintaining strong networks and mobilizing support, and (3) enhancing existing relationships by training members of the employee's social network in ways to be more supportive. The Caregiver Support Program was evaluated in a randomized field trial. Results indicate that the program was effective in improving the relationships between direct care staff participants and their house managers. However, other work relationships remained unaffected. The relationship between direct care staff and their house managers was the only work relationship for which both members of the interpersonal dyad participated in the program. The implications of these findings for health education practice and future research are discussed. PMID- 1757271 TI - The credentialing process. PMID- 1757270 TI - Training breast self-examination: a research review and critique. AB - Despite an increase in knowledge about breast cancer, a relatively low percentage of women practice breast self-examination (BSE) regularly and competently. This article reviews the BSE literature with a focus on training of BSE components, discrimination training, and the effectiveness of training procedures. Methodological issues such as the absence of control groups, lack of criteria for termination of training and reliance on self-reports of BSE frequency are identified weaknesses of BSE training studies. A theoretical analysis of BSE highlights potential difficulties in maintaining regular practice of BSE. Recommendations regarding training of proficient BSE skills and promoting regular practice of BSE are offered, and suggestions for further refinement of BSE training and directions for future research are discussed. Promising avenues of research in BSE training technology include discrimination training (on real or simulated breast tissue) together with computerized assessment of skill proficiency. PMID- 1757272 TI - Population genetics of human glyoxalases. AB - The gene for glyoxalase I (E.C. 4.4.1.5), Glo, has two alleles, Glo1 and Glo2, which are autosomally inherited in a co-dominant manner. Glo1 allele-frequency is highest in native Alaskan-Eskimo and Indian populations and decreases geographically south and east, to minimum levels in Aboriginal-Australian populations and native tribes in Papua New Guinea. There was no correlation between Glo1 frequency and incidence of insulin-dependent diabetes mellitus (IDDM). The frequencies of GLO phenotypes, Glo 1-1, Glo 1-2 and Glo 2-2, are disturbed in IDDM and there is a suggestion that IDDM patients with or without chronic, clinical complications have characteristic phenotype frequencies. PMID- 1757273 TI - Studies of the species barrier between Drosophila subobscura and D. madeirensis. I. The genetics of male hybrid sterility. AB - The genetics of hybrid male sterility between Drosophila subobscura and D. madeirensis were studied with the help of 20 markers in backcross males. A major effect resides in the sex chromosomes: backcross males with the X and Y of different origin (mad X-sub Y or sub X-mad Y) have very small and empty testes. In compatible combinations testes are of normal size but males may be sterile or fertile depending on the genetic constitution of their autosomes. Six autosomal factors affecting hybrid male fertility could be postulated. This estimation is based on the assumption of the absence of interaction between viability and fertility. The presence and the mode of such interaction may modify the number of sterility factors. PMID- 1757274 TI - Correlated variation of chromosomal inversion (3R)C and extra bristles in Drosophila melanogaster. AB - Chromosomal inversion In(3R)C and extra dorsocentral and scutellar macrochaetae are correlated in Asturian natural populations of Drosophila melanogaster in that selection for extra bristles produced an increase in In(3R)C frequency. In the present work two populations with significantly different frequencies of the In(3R)C inversion were created and a significant positive correlation between In(3R)C frequency and frequency of individuals carrying extra bristles was found. This result confirms the correlation between bristles and In(3R)C. In addition, the correlation between the two characters is also demonstrated at the individual level. PMID- 1757276 TI - Stop, look, and listen when your patients 'complain'. PMID- 1757275 TI - Transferrin polymorphism and genetic differentiation in Cervus elaphus L. (European red deer) populations. AB - A study of transferrin in 11 different European populations of Cervus elaphus as well as in one Cervus elephus x Cervus nippon hybrid population has revealed a polymorphism of this protein. Genetic analysis suggests that it is controlled by one gene locus with three codominant alleles. The allele frequencies allow a clear discrimination not only between the hybrid population and pure red deer but also between different Continental red deer populations. Comparison of the genotypic structures with the Hardy-Weinberg structure shows no significant deviation. Genetic variation within and differentiation between populations is evaluated for the transferrin gene locus using different measures. Average heterozygosities have been calculated for five populations including the results of previous studies on 14 other protein systems. Some management implications of the present results are discussed. PMID- 1757277 TI - PEF flow meter plays important role in asthma therapy. PMID- 1757278 TI - The efficacy of an endocervical brush in obtaining adequate Papanicolaou smears. AB - A total of 249 consecutive women attending a family planning clinic were entered in a study to determine the efficacy of the endocervical brush versus the cotton swab in obtaining routine Papanicolaou smears. Also investigated were whether the experience level of the smear taker contributed to the adequacy of the sample and whether simultaneous sampling by means of the spatula (an ectocervical sampling method) was justified. The use of the endocervical brush in place of the swab was found to improve cell collection by reducing the frequency of inadequate smears. The experience of the sample taker appeared not to be a factor in obtaining adequate smears. In 9% of the samples, only the ectocervical specimen was found to be satisfactory, indicating that use of the spatula should not be abandoned. PMID- 1757279 TI - Laboratory instruments for the physician's office laboratory: technology and cost benefits. AB - During the past two decades, medicine has witnessed the decentralization of laboratory testing from the hospital into the physician's office. This article focuses on the technical aspects of the instruments now available for laboratory testing in the physician's office. Consideration is given to specific instruments, methods, and cost-benefit. PMID- 1757280 TI - A proposal to modify research and scholarly activities during osteopathic residency training. PMID- 1757281 TI - Testicular metastasis from adenocarcinoma of the prostate. AB - Reported are two cases of prostate cancer metastatic to the testicle. Both patients underwent bilateral orchiectomies for treatment of symptomatic metastatic prostate cancer. Testicular metastasis was found incidentally in one patient and was suspected in the other. This site of spread is rare. The clinical significance and prognosis are discussed and the pertinent literature reviewed. PMID- 1757282 TI - Multiple aneurysms of the anterior communicating artery. AB - Multiple aneurysms of the anterior communicating artery are rare. The authors describe a patient who was admitted with a sudden, severe headache with radiation to the neck. Angiograms demonstrated filling of both anterior cerebral arteries and bilateral aneurysms arising from the origin of the anterior communicating artery. Both aneurysms were surgically verified and clipped. PMID- 1757283 TI - First order temporal properties of spontaneous and tone-evoked activity of auditory afferent neurones in the cochlear ganglion of the pigeon. AB - Spontaneous and tone-evoked single-unit activity was recorded from afferent neurones in the cochlear ganglion of the anaesthetized pigeon, and the data analysed in a way that allowed the physics of underlying mechanisms to be described. The periodicity of neural activity was quantified by Fourier analysis of the histogram of successive spike intervals. Spontaneous activity was quasiperiodic for 57% of neurones (average rate: 74 s-1); it was irregular for the remainder of neurones (average rate: 55 s-1). The preferred frequency (PF) of the quasiperiodic spontaneous activity was, on average, equal to the characteristic frequency (CF) of the neurone (70% of cases) or CF/2 (30%). This observation can be explained by supposing that preferred intervals of spontaneous activity are generated by noise passing through a filter tuned to the CF of the neurone; in most cases (70%) discharge was synchronized to CF, but in the others the neurone fired to every second cycle of the filtered signal. Consistent with this interpretation, for 79% of neurones, the modal interval of spontaneous activity was, on average, directly proportional to the CF-period, irrespective of whether preferred intervals were detected. The synchronization index at the PF was inversely related to the PF, and was quantified by the amplitude response of a first-order low-pass filter with cutoff frequency of 48 +/- 18 Hz. The spontaneous activity of 9% of neurones exhibited a second-harmonic component of the PF. For both tone-evoked and spontaneous activity, the observed synchronization indices of harmonics of the stimulus frequency or of the PF were consistent with an underlying exponential spike-generator function. If such a function does indeed govern spike generation, then it implies that the Shannon entropy of the probability density function of the instantaneous firing rate is near its maximum value and suggests that the system is close to statistical equilibrium. Single-tone rate-suppression was detected for 53% of those neurones that exhibited multiple preferred intervals of spontaneous activity. It is conjectured that the phenomena of quasiperiodic spontaneous activity and single tone rate-suppression are different aspects of a single presynaptic process. According to this model, we would expect to find these two phenomena in animals that have auditory fibres innervating electrically tuned hair cells, and that have stereocilia firmly coupled to a tectorial membrane. PMID- 1757284 TI - Time course of rate responses to two-tone stimuli in auditory nerve fibres in the guinea pig. AB - Peri-stimulus time histograms (PSTHs) were constructed from responses of auditory nerve fibres in anaesthetized guinea pigs. Acoustic stimuli consisted of pure tones, presented either as tone bursts, or in two-tone combinations in which a gated test tone was superimposed on a continuous excitatory tone at characteristic frequency (CF). The majority of the sample of fibres displayed two tone rate suppression (2TRS). The suppression was either a monotonic or a non monotonic function of the level of the superimposed test tone. Monotonic suppression of CF-driven rate occurred only for test tones at frequencies higher than CF, presented at levels up to the maximum available (approx. 100 dB SPL). For test tones below CF, 2TRS initially increased, then reverted towards excitation for higher levels of the test tone. Three levels were identified in non-monotonic, two-tone rate functions; (1) the threshold for rate suppression, (2) the maximally suppressing level and (3) the level (referred to as the balance point) at which average firing rate was restored to the background, CF-driven rate. PSTHs for two-tone responses obtained for test tone levels between the maximally-suppressing level and the balance point typically showed brief decrements (notches) in spike rate, at the onset and following the offset of the test tone. The latency, depth and duration of notches, however, depended on the level of the test tone, in a different manner for onset and offset. In some cases, without overt rate excitation above the probe-driven rate, the offset notch became more pronounced and of extended duration with increased level of the test tone, suggestive of adaptation to the test tone. Two-tone responses, in which rate exceeded the background, CF-driven rate, in general were preceded by a reduced onset notch and were followed by a longer-lasting depression of the background spike rate, typical of post-excitatory depression. Relative to responses obtained to the test tones presented alone, excitatory two-tone responses were of lower rate and were delayed by the onset notch. Onset notches sometimes preceded rate excitation in responses to single tones. Some features of the time course of rate suppression and excitation displayed in PSTHs for responses to one and two-tone stimuli seem inconsistent with current models of 2TRS. PMID- 1757285 TI - Masking and suppression in auditory nerve fibers of the goldfish, Carassius auratus. AB - The responses of single fibers of the auditory nerve of the goldfish (Carassius auratus) were recorded in response to two tones of different duration (20 ms 'signals' and 200 ms 'maskers') presented simultaneously or non-simultaneously. A single tone may produce excitation, adaptation, and suppression in auditory nerve fibers. For fibers with characteristic frequencies (CF) in the 200 to 400 Hz range, frequencies well above CF tend to produce suppression. If the net response to the masker tone is excitation, an added excitatory signal tone tends to increment the response in a way predictable from the rate-level function for the masker. A masker can attenuate the response to a signal as a result of a compressive and saturating response to the masker, and as a result of a low signal-to-masker ratio. If the net response to a masker tone is suppression, it effectively subtracts from signal excitation, causing 'suppressive masking.' In non-spontaneous fibers, suppression, additive excitatory effects, and adaptation can be revealed by responses to the signal in the absence of spike responses to the masker. In general, the ability of one tone (the masker) to reduce the response to a second tone (the signal) is greater in non-spontaneous fibers than in spontaneous fibers. These results also show that estimates of the frequency selectivity of many goldfish auditory nerve fibers will depend on whether the response of the fiber is defined by excitation, suppression, or both. The response of many fibers with CF in the 200-400 Hz region, as defined by excitation, can be masked or suppressed by a broad range of frequencies covering the effective hearing range of the goldfish. PMID- 1757286 TI - Binaural amplitude discrimination and the binaural masking-level difference. AB - Under certain conditions, amplitude discrimination is not a monotonic increasing function of signal-to-noise ratio. The non-monotonicity arises when the tones to be discriminated are presented 180 degrees out-of-phase at the observer's ears and just above their detection 'threshold' in noise that is in-phase at the observer's ears, and with 2-6-dB differences in amplitude. PMID- 1757287 TI - The effect of 'conditioning' exposures on hearing loss from traumatic exposure. AB - The role of 'conditioning' exposures as moderators of hearing loss produced by exposure to a higher level noise was explored using chinchillas. Monaural chinchillas were exposed to an octave band of noise centered at 0.5 kHz at 95 dB for six hours/day for ten days. The subjects were allowed to recover to pre exposure sensitivity and at five days after the last exposure they were re exposed to the same noise at 106 dB. Thresholds recorded at various time intervals following the second exposure were compared with those recorded in a control group exposed only to the higher level noise. The experimental animals were found to have less threshold shift at all stages of recovery. Results are discussed in the light of results of other related studies and possible mechanisms involved are hypothesized. PMID- 1757288 TI - Alternating current induced otoacoustic emissions in the guinea pig. AB - Injection of alternating current (AC) into the scala media of the guinea pig cochlea induced otoacoustic emissions (OAEs) at the frequency of the AC fundamental, together with harmonic and intermodulation distortion products. Although the waveform of the injected ACs was distorted, probably due to nonlinear polarization of the metal electrodes, and was composed of the fundamental plus distortion products of every order, only a few of the lowest order distortion products were selectively emitted with the fundamental. AC injection at a basal site extended the high frequency limit of OAEs. Electrical stimulation of the crossed olivocochlear bundle inhibited the sideband emissions with little change in the fundamental. OAE was reduced reversibly by temporary impairment of the cochlea due to exposure to fatiguing sound, by intravenous application of furosemide and by temporary anoxia. Irreversible reduction resulted from intracochlear perfusion with excess K+ solution, acoustic trauma and cardiac arrest. These facts imply that AC-induced OAE is not an artifact generated electrically; rather, such emissions originate in the cochlea and normal metabolic activity in the cochlea is essential. A proposed mechanism of generation includes two components: 1) electromechanical transduction from AC to mechanical vibration in the cochlea and 2) a distortion-producing process; the contribution of each component to the receptor mechanism is discussed. PMID- 1757289 TI - Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons. AB - Recovery of neural thresholds following a forward masker was measured for auditory neurons in anesthetized chinchillas. We find that recovery of forward masked thresholds is slower for low spontaneous-rate neurons compared to high spontaneous-rate neurons. In addition, we studied the dependence of the shape of PST histograms on the time between repetitions of a tone-burst. We find that for low spontaneous-rate neurons, peak onset responses increase in magnitude over a longer range of interstimulus intervals compared to high spontaneous-rate neurons. Both results are consistent with the conclusion that low spontaneous rate neurons take longer to recover from prior stimulation compared to high spontaneous-rate neurons. We suggest applications of this finding in psychophysical experiments to investigate the role of low spontaneous-rate neurons in intensity coding. PMID- 1757290 TI - Recovery from prior stimulation. II: Effects upon intensity discrimination. AB - We obtained just-noticeable differences (jnds) for the intensity of pure tones following a forward masker. The masker was a 100-ms burst of narrow-band noise centered at 1000 Hz presented at 90 dB SPL; the pure-tone signal was at 1000 Hz and was 25 ms in duration. The masker-signal delay was 100 ms. Under these conditions, there is no threshold shift for the detection of the pure-tone signal following the forward masker. In contrast with the absence of a forward-masker effect upon detection thresholds, unusually large midlevel (40-60 dB SPL) jnds were observed. These large midlevel jnds were measured as a function of signal delay, revealing that they are not completely recovered to the normal (unmasked) values by 400 ms. We interpret these data as a consequence of the slower recovery of low-spontaneous rate, high-threshold neurons following prior stimulation (Relkin and Doucet, 1990). These experiments may therefore provide psychophysical evidence that the low-spontaneous rate, high-threshold neurons are a necessary physiological component in the coding of the large dynamic range for intensity. In addition, the present data provide evidence that the assumption that the effect of forward masking is limited to 100-200 ms is inappropriate, as this recovery time does not necessarily apply to suprathreshold tasks. PMID- 1757291 TI - Postsynaptic inhibition can explain the concentration of short inter-spike intervals in avian auditory nerve fibres. AB - Spontaneous and sound-evoked single-unit activity was recorded from afferent neurones in the cochlear ganglion of the anaesthetized pigeon. The histogram of successive intervals of spontaneous activity of 51% of neurones exhibited more short intervals than expected from a Poisson point-process description of spike times; for another 43% of neurones the point-process was Poisson. A model of spike generation was developed to account for the concentration of short spike intervals. The proposed model contains inhibitory postsynaptic potentials at the afferent dendrite, in addition to the excitatory postsynaptic potentials. Not only does the model reproduce the first-order interval statistics of neural activity, but it provides a mechanism for improving phase-locking to the fundamental frequency of a sinusoid, and also offers an explanation for the presence of reciprocal synapses in the human cochlea. PMID- 1757292 TI - Effects of streptomycin on development of the apical structures of hair cells in the chick basilar papilla. AB - A single dose of streptomycin (166 mg/kg egg weight) was given to chick embryos 7 15 days after the beginning of incubation. Embryos were fixed 4-12 days later, and the hair cells examined by scanning and transmission electron microscopy. The highest proportion of abnormalities was produced by injections on or before the 11th day of incubation, later injections affecting a substantially smaller proportion of embryos. This suggests the possibility of a critical period for streptomycin ototoxicity in the chick. In addition to the normal signs of cellular degeneration, the most striking abnormality was a massive expansion in the apical surface, sometimes by a factor of 20, in area. The organisation of stereocilia was also commonly affected. The stereocilia could be broken up into multiple small separate bundles, and often there was a wide separation between the kinocilium and the stereocilia. Stereocilia tended to be reduced in number, fused, and either of abnormally large, small, or irregular diameters. Structures with the appearance of stereociliar cores often lay horizontally within the surface of the cuticular plate, sometimes running for 15 microns or more. Sometimes abnormal 'stereocilia' were expressed around the extreme margins of the cuticular plate. In addition, adjacent hair cells could show very different developmental stages, as though the development of some cells had been arrested. With all these changes, the short hair cells in the centre of a papillar cross section tended to be the most affected, with the tall hair cells and the short hair cells on the extreme inferior (i.e. abneural) edge being least affected. It is suggested that the streptomycin alters the balance of the different aspects of development of the hair cells. It might therefore be possible to use ototoxicity as a way of analysing hair-cell development. PMID- 1757293 TI - The effect of CO2- and O2-gas mixtures on laser Doppler measured cochlear and skin blood flow in guinea pigs. AB - The effects of carbogen (5% CO2: 95% O2) 10% CO2-in-air and 100% O2 on cochlear blood flow (CBF), skin blood flow (SBP), blood pressure (BP) and arterial blood gases were investigated in the anesthetized, respired or self-respiring guinea pig. In respired animals, CBF and SBF were increased with carbogen and 10% CO2-in air and decreased with O2. BP was elevated with each gas. In freely breathing animals, only 10% CO2-in-air caused a small increase in CBF; both carbogen and O2 caused CBF to decrease. SPF changes were similar in form, but larger than those seen in respirated subjects. No consistent change in BP was seen during breathing of these mixtures. Arterial PO2 was increased by carbogen and 10% CO2-in-air for both groups. PCO2 increased for both CO2 gas mixtures during forced respiration; but in free-breathing animals PCO2 only increased for 10% CO2-in-air (normal PCO2 values were maintained with carbogen thorough increased breathing rate). The observed changes in CBF were consistent with a balance between a combined vasoconstrictive effect of PO2 and vasodilation effect of PCO2 on cochlear vessels. Analysis of cochlear vascular conductivity (CBF/BP) indicated that vasodilation was significant only with 10% CO2-in-air in respirated animals. In all other conditions the increased CBF apparently reflects the increase profusion pressure associated with respiration of each gas. For clinical purposes, while carbogen does not appear to directly cause vasodilation of cochlear vessels it does lead to an increased oxygenation of the cochlea blood and would appear to avoid the cochlear vasoconstriction caused by 100% O2. PMID- 1757294 TI - Histochemical analysis of glycoconjugates in gelatinous membranes of the gerbil's inner ear. AB - The gelatinous membranes of the gerbil inner ear were analyzed histochemically for glycoconjugates with a battery of twenty horseradish peroxidase-conjugated lectins. Glycoconjugates with mannose (Man) and/or glucose (Glc), galactose (Gal), fucose (Fuc), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc) and N-acetylneuraminic acid (NeuAc) were detected in the tectorial and otolithic membranes and cupula. Differences in lectin reactivity were observed between tectorial and vestibular membranes and also among zones and between the medial and lateral regions of the middle zone of the tectorial membrane. The distribution of staining differed markedly for several lectins that bind specifically to GalNAc or to GlcNAc but vary in affinity for oligosaccharides containing these sugars in different sequences or linkages. The findings suggest presence of the terminal disaccharides GalNAc alpha 1,3Gal in tectorial membrane and Gal beta 1,3GalNAc in vestibular membranes. Lectin binding profiles provided evidence that the limbal zone's fibrous and attachment layers contain mainly O glycosidically linked oligosaccharides whereas the middle zone's medial fibrous layer contains both O- and N-linked chains. The remaining regions of the tectorial membrane contain mainly N-linked oligosaccharides with bisected biantennary type chains predominating. Additionally, the marginal band and the middle zone's basal layer contain abundant N-linked oligosaccharides with a triantennary structure. PMID- 1757295 TI - Influences of chemical sympathectomy and simulated weightlessness on male and female rats. AB - Maximum oxygen consumption (VO2max) has been shown to be reduced after periods of simulated weightlessness. To assess the role of the sympathetic nervous system in these reductions, Sprague-Dawley rats were either chemically sympathectomized (SYMX) or injected with saline (SHAM) and assigned to head-down suspension (HDS), horizontal restraint with the hindlimbs weight bearing (HWB), or cage-control (CC) conditions. VO2max, run time (RT), and mechanical efficiency (ME) were measured before suspension and on days 7 and 14. Male and female SHAM HDS groups exhibited reduced measures of VO2max (12-13%) after 7 and 14 days, and this decrease was attenuated in the SYMX and HWB rats. HDS resulted in a significant reduction in RT (9-15%) in both the male and female rats, and ME was significantly reduced after HDS in male and female SYMX and male SHAM rats (23 33%) but not in the female SHAM rats. Lesser reductions in ME were observed in the HWB rats. HDS and HWB were associated with lower body, fat-free, and fat masses, which were similar in male and female rats as well as for the SHAM and SYMX conditions. In a related HDS experiment with normal rats, plasma norepinephrine and epinephrine were increased by 53 and 42% after 7 days, but only epinephrine returned to baseline after 14 days. It was concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. The mechanism(s) remains unclear at this time. PMID- 1757296 TI - Effects of maternal exercise on liver and skeletal muscle glycogen storage in pregnant rats. AB - To examine the effects of maternal exercise on liver and skeletal muscle glycogen storage, female Sprague-Dawley rats were randomly divided into control, nonpregnant runner, pregnant nonrunning control, pregnant runner, and prepregnant exercised control groups. The exercise consisted of treadmill running at 30 m/min on a 10 degree incline for 60 min, 5 days/wk. Pregnancy alone, on day 20 of gestation, decreased maternal liver glycogen content and increased red and white gastrocnemius muscle glycogen storage above control values (P less than 0.05). In contrast, exercise in nonpregnant animals augmented liver glycogen storage and also increased red and white gastrocnemius glycogen content (P less than 0.05). By combining exercise and pregnancy, the decrease in liver glycogen storage in the pregnant nonexercised condition was prevented in the pregnant runner group and more glycogen was stored in both the red and white portions of the gastrocnemius than all other groups (P less than 0.05). Fetal body weight was greatest (P less than 0.05) in the pregnant runner group and lowest (P less than 0.05) in the prepregnant exercise control group. These results demonstrate that chronic maternal exercise may change maternal glycogen storage patterns in the liver and skeletal muscle with some alteration in fetal outcome. PMID- 1757297 TI - Origin of cardiac-related thoracic electrical impedance variations in lambs. AB - Cardiac-related deflections in thoracic electrical impedance have been thought to correlate sufficiently well with cardiac stroke volume to be used as the basis for a noninvasive estimation of cardiac output. To determine more precisely the physiological origin of the impedance deflection (DZ), we regarded right ventricular stroke volume (SVa) as the sum of two components: 1) that part of SVa responsible for the transient increment in pulmonary blood volume within a cardiac cycle, SVa-v and 2) the remaining part of SVa, (SVa-SVa-v). SVa-v was measured in lambs by integration of the difference between pulmonary arterial and pulmonary venous flow. SVa and its components were varied experimentally by opening and closing an aorticocaval shunt or by inflating and deflating a cuff implanted around the pulmonary artery. DZ was measured using a tetrapolar disk electrode system. Multivariate linear regression analysis revealed that SVa-v had a significant positive effect on DZ, and, at the same time, (SVa-SVa-v) had a significant negative effect on DZ. In the pulmonary artery occluder model, the positive effect of SVa-v dominated the opposing negative effect of (SVa - SVa-v) so that the net effect of SVa on DZ was positive and significant. In the aorticocaval shunt model, these effects opposed each other to the extent that there was no significant correlation between SVa and DZ. These results shed new light on the physiological origin of DZ. They also demonstrate that use of DZ to measure acute changes in cardiac output may yield misleading results. Changes or the lack of changes in thoracic electrical impedance do not necessarily reflect cardiac output status. PMID- 1757298 TI - Hypoxia potentiates exercise-induced sympathetic neural activation in humans. AB - Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757299 TI - Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats. AB - The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min 1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration. PMID- 1757300 TI - Effect of alkalosis on maximum oxygen uptake in rats acclimated to simulated altitude. AB - The objective of the present experiments was to determine whether prevention or moderation of exercise acidosis would influence arterial blood oxygenation and exercise capacity in hypoxia. The effect of administration of 0.3 M NaHCO3 (3 ml/100 g) on maximum O2 uptake (VO2max) and arterial blood oxygenation was determined in rats acclimated to simulated altitude (370-380 Torr barometric pressure) for 3 wk (HxBic) and in normoxic littermates (NxBic). Controls were simulated-altitude (HxNaCl) and normoxic rats (NxNaCl) given 0.3 M NaCl. Inspiratory PO2 during treadmill exercise was approximately 70 Torr for hypoxic rats and 140-145 Torr for normoxic rats. VO2max was 18% higher in HxBic than in HxNaCl (62.8 + 1.6 vs. 53.1 + 1.0 ml STPD.min-1.kg-1, respectively, P less than 0.05) and only 8% higher in NxBic than in NxNaCl (74.0 + 1.1 vs. 68.7 + 1.5 ml STPD.min-1.kg-1, respectively, P less than 0.05). Exercise in HxNaCl resulted in a decrease in arterial O2 concentration (CaO2), which was largely due to a pH induced decrease in O2 saturation of arterial blood, and occurred despite an increase in arterial PO2. NaHCO3 moderated the acidosis of exercise and largely attenuated the decrease in CaO2. The effects of acidosis and bicarbonate on CaO2 were much less evident in the normoxic controls. There was an almost linear relationship between VO2max and the corresponding CaO2 for all four groups, suggesting that the effect of NaHCO3 on VO2max may be related to moderation of the decrease in CaO2. PMID- 1757301 TI - Prevention of H2O2 generation by monoamine oxidase protects against CNS O2 toxicity. AB - Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21-40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats. PMID- 1757302 TI - Dynamic regulation of leg vasomotor tone in patients with chronic heart failure. AB - We examined the central hemodynamic (n = 5) and leg blood flow (n = 9) responses to one- and two-leg bicycle exercise in nine ambulatory patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction 17 +/- 9%). During peak one- vs. two-leg exercise, leg blood flow (thermodilution) tended to be higher (1.99 +/- 0.91 vs. 1.67 +/- 0.91 l/min, P = 0.07), whereas femoral arteriovenous oxygen difference was lower (13.6 +/- 3.1 vs. 15.0 +/- 2.9 ml/dl, P less than 0.01). Comparison of data from exercise stages matched for single-leg work rate during one- vs. two-leg exercise demonstrated that cardiac output was similar while both oxygen consumption and central arteriovenous oxygen differences were lower, indicating relative improvement in the cardiac output response at a given single-leg work rate during one-leg exercise. This was accompanied by higher leg blood flow (1.56 +/- 0.76 vs. 1.83 +/- 0.72 l/min, P = 0.02) and a tendency for leg vascular resistance to be lower (92 +/- 54 vs. 80 +/ 48 Torr.l-1.min, P = 0.08) without any change in blood lactate. These data indicate that, in patients with chronic heart failure, leg vasomotor tone is dynamically regulated, independent of skeletal muscle metabolism, and is not determined solely by intrinsic abnormalities in skeletal muscle vasodilator capacity. Our results suggest that relative improvements in central cardiac function may lead to a reflex release of skeletal muscle vasoconstrictor tone in this disorder. PMID- 1757303 TI - Coincident thresholds in intracellular phosphorylation potential and pH during progressive exercise. AB - Dynamic changes in intracellular phosphocreatine (PCr), inorganic phosphate (Pi), and pH in human forearm muscle were studied from rest through heavy exercise by means of a ramp exercise protocol and 31P nuclear magnetic resonance spectroscopy. Eighteen healthy volunteers performed an isotonic wrist flexion exercise of repeated contractions at a frequency of 0.5 Hz. Work rate was increased continuously (ramped) at approximately 0.13 W each minute from 0.34 to 1.5 W or until fatigue. Pi/PCr was used as an estimate of the cellular phosphorylation potential of the muscle. Exercise caused a progressive increase in Pi/PCr with an initial slow and later fast component. The transition between these components was distinct and corresponded to the onset of pH decline in all subjects. These changes in Pi/PCr and pH were best fit (P less than 0.05) by a piecewise linear regression model with a break point or threshold. Repeated ramp testing of six subjects showed that the threshold was reproducible (r = 0.98). The results of this study demonstrate the existence of an intracellular metabolic threshold and suggest that indirect threshold measures (lactate and ventilatory thresholds) may reflect events at the cellular level. PMID- 1757304 TI - Carbohydrate feedings before, during, or in combination improve cycling endurance performance. AB - This study examined the effects of no carbohydrate (PP), preexercise carbohydrate feeding (CP), carbohydrate feedings during exercise (PC), and the combination of carbohydrate feedings before and during exercise (CC) on the metabolic responses during exercise and on exercise performance. Nine well-trained cyclists exercised at 70% of maximal O2 uptake until exhaustion. Blood glucose peaked 30 min after the preexercise carbohydrate feeding and at the start of exercise was 25% below the prefeeding concentration (4.76 mM). At exhaustion, glucose had declined to 3.8 (PP), 4.0 (CP), 4.6 (PC), and 5.0 mM (CC). Insulin was 300% above basal (7 microU/ml) at the start of exercise for CC and CP and returned to baseline by 120 min of exercise. When carbohydrates were consumed, the rate of carbohydrate oxidation was significantly higher throughout exercise than during PP. Total work produced during exercise was 19-46% (P less than 0.05) higher when carbohydrates were consumed. Time to exhaustion was 44% (CC), 32% (PC), and 18% (CP) greater than PP (201 min; P less than 0.05). Performance was improved by ingestion of carbohydrates before and/or during exercise; performance was further improved by their combination. This is probably the result of enhanced carbohydrate oxidation, especially during the later stages of exercise. PMID- 1757305 TI - Mechanism of failure of recovery from hypoxic apnea by gasping in 17- to 23-day old mice. AB - The mechanism of failure of autoresuscitation from hypoxic apnea in 17- to 23-day old (weanling) Swiss Webster related/J mice was investigated by recording electrocardiogram (ECG) and ventilation in adult, weanling, and 11-day-old mice. Hypoxic apnea was induced with 97% N2-3% CO2. O2 (21% or 50% O2) or 97% N2-3% CO2 was given at the onset of apnea. The ECG showed no arrhythmias predictive of failure of autoresuscitation. The first indication of failure was a progressive fall in gasp volume ("run down"). This pattern also occurred in animals given continuous 97% N2-3% CO2 and was significantly different from that in mice that survived. Gasping duration in 97% N2 was longer in weanlings than adults but shorter than in 11 day olds. Respiratory and heart rate recovery were more rapid in adults than in weanlings. Although recovery in high O2 was more rapid, the survival rate was not increased. The lack of effect of high O2 on survival and the virtually identical pattern of gasping in mice dying in 97% N2 and air leads us to conclude that in mice that fail to autoresuscitate little or no O2 reaches the medullary respiratory centers. We speculate that this may be due to increased vulnerability of cardiac muscle to anoxia in 17- to 23-day-old mice, resulting in early and severe heart failure. PMID- 1757306 TI - Metabolism during normal, fragmented, and recovery sleep. AB - Average metabolic data (O2 uptake and CO2 output) were obtained for each 3-min period during consecutive nights of normal, experimentally fragmented, and recovery sleep in a group of 12 normal young adult males. Naturally occurring arousals and awakenings resulted in a characteristic increase in metabolism on the baseline night. The placement of brief frequent experimental arousals on the following night resulted in significantly increased metabolism throughout the night and significantly decreased sleep restoration as measured by morning performance, mood, and alertness tests, even though total sleep time was minimally reduced. Metabolic variables were significantly decreased compared with baseline on the nondisturbed recovery night that followed the sleep fragmentation night. The data cannot be used to infer that increased metabolism during sleep causes nonrestorative sleep, but the direction and time course of metabolic change accompanying arousal are consistent with that hypothesis. PMID- 1757307 TI - Carrying loads with springy poles. AB - People throughout Asia use springy bamboo poles to carry the loads of everyday life. These poles are a very compliant suspension system that allows the load to move along a nearly horizontal path while the person bounces up and down with each step. Could this be an economical way to carry loads inasmuch as no gravitational work has to be done to lift the load repeatedly? To find out, an experiment was conducted in which four male subjects ran at 3.0 m/s on a motorized treadmill with no load and while carrying a load equal to 19% body wt with compliant poles. Oxygen consumption rate, vertical ground reaction force, and the force exerted by the load on the shoulders were measured. Oxygen consumption rate increased by 22%. The same increase has previously been observed when loads are carried with a backpack. Thus compliant poles are not a particularly economical method of load carriage. However, pole suspension systems offer important advantages: they minimize peak shoulder forces and loading rates. In addition, the peak vertical ground reaction force is only slightly increased above unloaded levels when loads are carried with poles. PMID- 1757308 TI - Dynamic response of the peripheral chemoreflex loop to changes in end-tidal O2. AB - We studied the peripheral ventilatory response dynamics to changes in end-tidal O2 tension (PETO2) in 13 cats anesthetized with alpha-chloralose-urethan. The arterial O2 tension in the medulla oblongata was kept constant using the technique of artificial perfusion of the brain stem. At constant end-tidal CO2 tension, 72 ventilatory on-responses due to stepwise changes in PETO2 from hyperoxia (45-55 kPa) to hypoxia (4.7-9.0 kPa) and 62 ventilatory off-responses due to changes from hypoxia to hyperoxia were assessed. We fitted two exponential functions with the same time delay to the breath-by-breath ventilation and found a fast and a slow component in 85% of the ventilatory on-responses and in 76% of the off-responses. The time constant of the fast component of the ventilatory on response was 1.6 +/- 1.5 (SD) s, and that of the off-response was 2.4 +/- 1.3 s; the gain of the on-response was smaller than that of the off-response (P = 0.020). For the slow component, the time constant of the on-response (72.6 +/- 36.4 s) was larger (P = 0.028) than that of the off-response (43.7 +/- 28.3 s), whereas the gain of the on-response exceeded that of the off-response (P = 0.031). We conclude that the ventilatory response of the peripheral chemoreflex loop to stepwise changes in PETO2 contains a fast and a slow component. PMID- 1757309 TI - Pulmonary vascular smooth muscle: biochemical and mechanical developmental changes. AB - To evaluate the developmental changes in pulmonary vascular smooth muscle contractile protein content, mechanical properties, and their contribution to the high resistance characteristic of the fetal and immediate neonatal period, we studied pulmonary vessels of fetal, newborn, and adult sheep, as well as newborn and adult pigs. Strips of the second- through fifth-generation vessels were dissected, and their content of tissue total smooth muscle cell protein, myosin, and actin-to-myosin ratio were measured; the mechanical properties of the second generation vascular strips were also studied. For all ages the smooth muscle protein and myosin content of the second-generation vessels were significantly greater than for the lower pulmonary vascular orders (P less than 0.05). The myosin content in fetal sheep (0.77 +/- 0.03 micrograms/mg wet tissue) was similar to that of the newborn (0.79 +/- 0.04) and adult (0.86 +/- 0.05). However, the smooth muscle protein content (7.94 +/- 0.21 micrograms/mg wet tissue) and the actin-to-myosin ratio of the pulmonary vascular tissue of the fetus (1.00 +/- 0.04) were lower (P less than 0.01) in the fetal than in the newborn (9.16 +/- 0.26 and 1.60 +/- 0.12) and adult (9.38 +/- 0.3 and 1.60 +/- 0.11, respectively). No differences were observed for these parameters between the newborn and adult pig. Stress (16.5 +/- 1.7 mN/mm2) and the maximum shortening capacity (13.0 +/- 1.5% of optimal length) in the newborn pulmonary vascular strips were significantly greater than for the fetus (6.8 +/- 1.4 and 5.9 +/- 1.0, respectively) but similar to those of the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757310 TI - Autonomic control of heart rate during exercise studied by heart rate variability spectral analysis. AB - Spectral analysis of heart rate variability (HRV) might provide an index of relative sympathetic (SNS) and parasympathetic nervous system (PNS) activity during exercise. Eight subjects completed six 17-min submaximal exercise tests and one resting measurement in the upright sitting position. During submaximal tests, work rate (WR) was increased for the initial 3 min in a ramp fashion until it reached constant WRs of 20 W, or 30, 60, 90, 100, and 110% of the predetermined ventilatory threshold (Tvent). Ventilatory profile and alveolar gas exchange were monitored breath by breath, and beat-to-beat HRV was measured as R R intervals of an electrocardiogram. Spectral analysis was applied to the HRV from 7 to 17 min. Low-frequency (0-0.15 Hz) and high-frequency (0.15-1.0 Hz) areas under power spectra (LO and HI, respectively) were calculated. The indicator of PNS activity (HI) decreased dramatically (P less than 0.05) when the subjects exercised compared with rest and continued to decrease until the intensity reached 60% Tvent. The indicator of SNS activity (LO/HI) remained unchanged up to 100% Tvent, whereas it increased abruptly (P less than 0.05) at 110% Tvent. The results suggested that (cardiac) PNS activity decreased progressively from rest to a WR equivalent to 60% Tvent, and SNS activity increased only when exercise intensity exceeded Tvent. PMID- 1757311 TI - Coarse-graining spectral analysis: new method for studying heart rate variability. AB - Heart rate variability (HRV) spectra are typically analyzed for the components related to low- (less than 0.15 Hz) and high- (greater than 0.15 Hz) frequency variations. However, there are very-low-frequency components with periods up to hours in HRV signals, which might smear short-term spectra. We developed a method of spectral analysis suitable for selectively extracting very-low-frequency components, leaving intact the low- and high-frequency components of interest in HRV spectral analysis. Computer simulations showed that those low-frequency components were well characterized by fractional Brownian motions (FBMs). If the scale invariant, or self-similar, property of FBMs is considered a new time series (x') was constructed by sampling only every other point (course graining) of the original time series (x). Evaluation of the cross-power spectra between these two (Sxx') showed that the power of the FBM components was preserved, whereas that of the harmonic components vanished. Subtraction of magnitude of Sxx from the autopower spectra of the original sequence emphasized only the harmonic components. Application of this method to HRV spectral analyses indicated that it might enable one to observe more clearly the low- and high-frequency components characteristic of autonomic control of heart rate. PMID- 1757312 TI - Optimizing athletic performance by influence curves. AB - Recent application of modeling techniques to physical training has opened the possibility for prediction from training. Solution of the inverse problem, determining a training program to produce a desired performance at a specific time, is also possible and may yield strategies for achieving better training and tapering (complete or relative rest for a period before competition) regimens for competitive athletes. A mathematical technique derived from model theory is described in this paper that allows the design of an optimal strategy of physical preparation for an individual to do well in a single future competitive event or cluster of events. Simulation results, using default parameters of a training model, suggest that presently accepted forms of taper for competition may remain too rigorous and short in duration to achieve the best result possible from the training undertaken. PMID- 1757313 TI - Estimation of time-varying respiratory mechanical parameters by recursive least squares. AB - Continuous estimation of time-varying respiratory mechanical parameters is required to fully characterize the time course of bronchoconstriction. To achieve such estimation, we developed an estimator that uses the recursive linear least squares algorithm to fit the equation Ptr = RV + EV + K to measurements of tracheal pressure (Ptr) and flow (V). The volume (V) is obtained by numerical integration of V. The estimator has a finite memory with length into the past at each point in time that varies inversely with the difference between the current measurement of Ptr and that predicted by the model, to allow the algorithm to track rapidly varying parameters (R, E, and K). V usually exhibits significant drift and must be corrected. Of the several correction methods investigated, subtraction of the recursively weighted average of V before integration to V was found to perform best. The estimator was tested on simulated noisy data where it successfully followed a fivefold increase in R and a twofold increase in E occurring over 10 s. Three dogs and two cats were anesthetized, paralyzed, tracheostomized, and challenged with a bolus of methacholine (approximately 13 mg/kg iv). Increases of 3- to 10-fold were observed in R and 2- to 3-fold in E, beginning within 10-40 s after the bolus injection. In some animals we found that the increase in E occurred more slowly than that in R, which the V signal suggested was due to dynamic hyperinflation of the lungs. These results demonstrate that our recursive estimator is able to track rapid changes in respiratory mechanical parameters during bronchoconstrictor challenge. PMID- 1757314 TI - Hemodynamic basis for cocaine-induced pulmonary edema in dogs. AB - We tested the hypothesis that cocaine-induced impairment of left ventricular function results in cardiogenic pulmonary edema. Mongrel dogs, anesthetized with alpha-chloralose, were injected with two doses of cocaine (5 mg/kg iv) 27 min apart. Cocaine produced transient decreases in aortic and left ventricular systolic pressures that were followed by increases exceeding control. As aortic pressure recovered, left ventricular end-diastolic, left atrial (Pla), pulmonary arterial (Ppa), and central venous pressures rose. Cardiac output and stroke volume were reduced when measured 4-5 min after cocaine administration. Peak Ppa and Pla were 31 +/- 5 (SE) mmHg (range 17-51 mmHg) and 26 +/- 5 mmHg (range 12-47 mmHg), respectively. Increases in extravascular lung water content (4.10 to 6.24 g H2O/g dry lung wt) developed in four animals in which Pla exceeded 30 mmHg. Analysis of left ventricular function curves revealed that cocaine depressed the inotropic state of the left ventricle. Cocaine-induced changes in hemodynamics spontaneously recovered and could be elicited again by the second dose of the drug. Our results show that cocaine-induced pulmonary hypertension, associated with decreased left ventricular function, produces pulmonary edema if pulmonary vascular pressures rise sufficiently. PMID- 1757315 TI - Role of NaCl cotransport in cerebrospinal fluid production: effects of loop diuretics. AB - Cerebrospinal fluid (CSF) is secreted primarily by the choroid plexus (CP) located in the cerebral ventricles. Although much is known about ionic composition of cisternal CSF, the mechanisms involved in secretion of CSF in mammals are still not understood. The main aim of this report is to critically review the role of NaCl cotransport carrier in CSF production. On the basis of the studies in the literature, a model for CSF production by the CP is proposed. In this model, CP cells are assumed to be equipped with an NaCl cotransport carrier located on the basolateral (blood-facing) membrane. Because Na+ and Cl- are the two principal ions in CSF, their continued secretions into cerebral ventricles by CP cells require an adequate intracellular supply, which may be guaranteed by the NaCl cotransport carrier. Although this appears to be a reasonable assumption, making the processes involved in CSF production similar to those of other secretory epithelial cells, the presence of such a carrier in mammalian CP remains controversial. The reasons for this controversy are critically reviewed, and some suggestions for further studies are made. PMID- 1757316 TI - Effect of dietary restriction and/or exercise on 23-h metabolic rate and body composition in female rats. AB - This study examined the effects of three levels of dietary intake [ad libitum fed (AL), moderately severe (MSR), and severe restriction (SR)] and two levels of exercise [cage confinement (CC) and exercise training (E)] on 23-h resting metabolic rate (RMR) and body composition in 47 female Sprague-Dawley rats. At the end of the 9-wk study, the MSR and SR groups weighed approximately 81 and 61%, respectively, of the AL-CC group. RMR was depressed for the MSR and SR groups compared with the AL-CC group. This was true whether expressed on an absolute (ml/min) or relative (ml.min-1.kg-0.75) basis. On a relative basis, which accounts for changes caused by weight loss alone, the RMR decreased by approximately 12 and 19%, respectively, for the MSR and SR groups compared with the AL-CC group. Although E resulted in significant differences in fat mass, percent fat, percent water, and heart mass between the AL groups, there were no significant differences between E and CC groups at either the MSR or SR level of dietary intake for any of the variables measured (i.e., body composition, muscle mass, RMR). Thus E does not appear to affect the composition of lost weight or RMR during diet-induced weight loss for female rats of normal weight. PMID- 1757317 TI - Effect of free radicals on pulmonary vascular response to acetylcholine. AB - We describe a model of pulmonary endothelial injury caused by electrolysis generated free radicals. Rabbit lungs were perfused in situ with Krebs solution at 37 degrees C containing 30 microM indomethacin. Electrolysis of this solution for 2 min, with a constant DC current of 20 mA, caused pulmonary vasoconstriction during the passage of current and converted subsequent acetylcholine-induced vasodilation to vasoconstriction. Electrolysis also inhibited endothelial dependent vasodilation due to the calcium ionophore A23187 but not that due to sodium nitroprusside, suggesting that smooth muscle function was unaltered, while that of the endothelium of the lung is specifically modified by the stimulus. These effects were prevented by a mixture of superoxide dismutase and catalase or by sodium salicylate, which removes hydroxyl radicals from solution after electrolysis. Electrolysis-induced endothelial damage was less functionally obvious when electrolysis was applied during recirculation of Krebs solution, perhaps because recirculating perfusion may trigger release of either free radical scavengers or other protective substances. This technique offers a simple reproducible model to study free radical-related damage of endothelium in the intact lung. PMID- 1757318 TI - A nonlinear viscoelastic model of lung tissue mechanics. AB - There have been a number of attempts recently to use linear models to describe the low-frequency (0-2 Hz) dependence of lung tissue resistance (Rti) and elastance (Eti). Only a few attempts, however, have been made to account for the volume dependence of these quantities, all of which require the tissues to be plastoelastic. In this paper we specifically avoid invoking plastoelasticity and develop a nonlinear viscoelastic model that is also capable of accounting for the nonlinear and frequency-dependent features of lung tissue mechanics. The model parameters were identified by fitting the model to data obtained in a previous study from dogs during sinusoidal ventilation. The model was then used to simulate pressure and flow data by use of various types of ventilation patterns similar to those that have been employed experimentally. Rti and Eti were estimated from the simulated data by use of four different estimation techniques commonly applied in respiratory mechanics studies. We found that the estimated volume dependence of Rti and Eti is sensitive to both the ventilation pattern and the estimation technique, being in error by as much as 217 and 22%, respectively. PMID- 1757319 TI - How is maximal expiratory flow reduced in canine postpneumonectomy lung growth? AB - Six dogs underwent left pneumonectomy (P) at 10 wk of age, while four littermates had a sham operation (C). All dogs were studied at 26 wk of age. Pressure capsules were placed on the right lung to measure lobar alveolar pressures and flows, and a Pitot-static tube was used to measure dynamic intrabronchial pressures. Vital capacity and lung elastic recoil did not differ between P and C. At all lung volumes studied, maximum expiratory flows (Vmax) in P were substantially lower than in C. Choke points in P were located more peripherally than in C. In central airways subjected to the same distending pressure, calculated cross-sectional area was significantly lower in P than in C, indicating different bronchial area-pressure behavior. In P, frictional resistances of the right lower, middle, and cardiac lobes were significantly higher than those in C. These results indicate that the reduction in Vmax in P was greater than would have been expected on the basis of reductions in central airway diameter alone. We calculated that, in the middle vital capacity range, approximately 60% of the decrease in Vmax was due to changes in dynamic central airways properties, and approximately 40% was due to increased lobar frictional resistance related to compensatory growth. PMID- 1757320 TI - Multiple-breath washout experiments in rat lungs. AB - Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VDF(n) and VDB(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VDF and VDB were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange. PMID- 1757321 TI - Single-breath washout experiments in rat lungs. AB - Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2-5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (approximately 15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were greater than 1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree. PMID- 1757322 TI - Mechanics of running under simulated low gravity. AB - Using a linear mass-spring model of the body and leg (T. A. McMahon and G. C. Cheng. J. Biomech. 23: 65-78, 1990), we present experimental observations of human running under simulated low gravity and an analysis of these experiments. The purpose of the study was to investigate how the spring properties of the leg are adjusted to different levels of gravity. We hypothesized that leg spring stiffness would not change under simulated low-gravity conditions. To simulate low gravity, a nearly constant vertical force was applied to human subjects via a bicycle seat. The force was obtained by stretching long steel springs via a hand operated winch. Subjects ran on a motorized treadmill that had been modified to include a force platform under the tread. Four subjects ran at one speed (3.0 m/s) under conditions of normal gravity and six simulated fractions of normal gravity from 0.2 to 0.7 G. For comparison, subjects also ran under normal gravity at five speeds from 2.0 to 6.0 m/s. Two basic principles emerged from all comparisons: both the stiffness of the leg, considered as a linear spring, and the vertical excursion of the center of mass during the flight phase did not change with forward speed or gravity. With these results as inputs, the mathematical model is able to account correctly for many of the changes in dynamic parameters that do take place, including the increasing vertical stiffness with speed at normal gravity and the decreasing peak force observed under conditions simulating low gravity. PMID- 1757323 TI - Fluid replacement and glucose infusion during exercise prevent cardiovascular drift. AB - This study examined the influence of both hydration and blood glucose concentration on cardiovascular drift during exercise. We first determined if the prevention of dehydration during exercise by full fluid replacement prevents the decline in stroke volume (SV) and cardiac output (CO) during prolonged exercise. On two occasions, 10 endurance-trained subjects cycled an ergometer in a 22 degrees C room for 2 h, beginning at 70 +/- 1% maximal O2 uptake (VO2max) and in a euhydrated state. During one trial, no fluid (NF) replacement was provided and the subject's body weight declined 2.09 +/- 0.19 kg or 2.9%. During the fluid replacement trial (FR), water was ingested at a rate that prevented body weight from declining after 2 h of exercise (i.e., 2.34 +/- 0.17 1/2 h). SV declined 15% and CO declined 7% during the 20- to 120-min period of the NF trial while heart rate (HR) increased 10% and O2 uptake (VO2) increased 6% (all P less than 0.05). In contrast, SV was maintained during the 20- to 120-min period of FR while HR increased 5% and thus CO actually increased 7% (all P less than 0.05). Rectal temperature, SV, and HR were similar during the 1st h of exercise during NF and FR. However, after 2 h of exercise, rectal temperature was 0.6 degree C higher (P less than 0.05) and SV and CO were 11-16% lower (P less than 0.05) during NF compared with FR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757324 TI - Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h. AB - As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0-1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of vital capacity (FEF25-75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25-75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse. PMID- 1757325 TI - Partitioning of pulmonary responses to inhaled methacholine in puppies. AB - Twelve open-chest mongrel puppies, 8-10 wk old, were studied to localize the site of action of inhaled methacholine within the lungs. Six puppies were challenged with methacholine aerosols and six were challenged with an equal number of nebulizations of normal saline (control group). Pulmonary mechanics were measured during mechanical ventilation and after midexpiratory flow interruptions. Alveolar pressure was measured to allow the partitioning of pulmonary mechanics into airway and tissue components. Good matching between airway opening and alveolar pressures was seen throughout the study. After methacholine challenge, lung resistance increased fivefold. Increases in airway resistance and in the parameters reflecting tissue viscoelastic properties contributed to this increase in lung resistance. Dynamic lung elastance also increased threefold. The response of the methacholine group was statistically different from that of the control group. These data indicate that both the airways and pulmonary parenchyma contribute to the response to inhaled methacholine in 8- to 10-wk-old puppies. PMID- 1757326 TI - Short-term potentiation of breathing in humans. AB - The purpose of this study was to determine if the increase in ventilation induced by hypoxic stimulation of the carotid bodies (CB) persists after cessation of the stimulus in humans. I reasoned that a short-term potentiation (STP) of breathing, sometimes called an "afterdischarge," could be unmasked by combining hypoxia with exercise, because ventilation increases synergistically under these conditions. Seven young healthy men performed mild bicycle exercise (30% peak power) while breathing O2 for 1.5 min ("control" state), and their CB were then stimulated by 1.5 min of hypoxic exercise (10% O2--balance N2). CB stimulation was then terminated by changing the inspirate back to O2 as exercise continued. Inspiratory and expiratory duration (TI and TE) and inspiratory flow and its time integral [tidal volume (VT)] were measured with a pneumotachometer. Inspired minute ventilation (VI) and mean inspiratory flow (VT/TI) declined exponentially after the cessation of CB stimulation, with first-order time constants of 28.6 +/ 6.7 and 24.6 +/- 1.6 (SD) s, respectively. The slow decay of VI was due primarily to potentiation of both TI and TE, although the effect on the latter predominated. Additional experiments in six subjects showed that brief intense CB stimulation with four to five breaths of N2 during mild exercise induced STP of similar magnitude to that observed in the hypoxic exercise experiments. Finally, the imposition of hyperoxia during air breathing exercise at a level of respiratory drive similar to that induced by the hypoxic exercise did not change VI significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757327 TI - Cigarette smoke in lungs evokes reflex increase in tracheal submucosal gland secretion in dogs. AB - Stimulation of pulmonary C-fibers (PCs) by capsaicin and of rapidly adapting receptors (RARs) by reduced lung compliance reflexly increases airway submucosal gland secretion in dogs. Because both PCs and RARs are stimulated by cigarette smoke (nicotine being the primary stimulus), we performed experiments in anesthetized open-chest artificially ventilated dogs (with aortic nerves cut) to determine whether cigarette smoke reflexly stimulates airway secretion. We measured submucosal gland secretion by counting the hillocks in a 1.2-cm2 field of tracheal epithelium coated with tantalum dust. Secretion was stimulated by delivery of 40-320 ml smoke from high-nicotine cigarettes to the lower trachea, secretion rate increasing from 7.4 +/- 1.3 to 48.1 +/- 5.1 hillocks.cm-2.min-1. Results of cutting the pulmonary vagal branches or carotid sinus nerves or both indicated that the secretory response was initiated by stimulation of lower respiratory vagal afferents and augmented several seconds later by stimulation of carotid chemoreceptors. Results of cooling the cervical vagus nerves to 7 and 0 degrees C indicated that most of the vagally mediated increase in secretion was due to stimulation of afferent lung C-fibers. PMID- 1757328 TI - Elevated interstitial fluid volume in rat soleus muscles by hindlimb unweighting. AB - Hindlimb unweighting is a commonly used model to study skeletal muscle atrophy associated with disuse and exposure to microgravity. However, a discrepancy in findings between single fibers and whole muscle has been observed. In unweighted solei, specific tension deficits are greater in whole muscle than in single fibers. Also, metabolic enzyme activity when normalized per gram of mass is depressed in whole muscle but not in single fibers. These observations suggest that soleus muscle interstitial fluid volume may be elevated with atrophy caused by unweighting in rats. The purpose of this study was to determine if soleus muscle atrophy induced by unweighting is accompanied by alterations in muscle interstitial fluid volume and to calculate the effect of any such alterations on the muscle specific tension (N/cm2 muscle cross-sectional area). Nine female Wistar rats (200 g) were hindlimb unweighted (HU) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147.8 +/- 2.3 mg; HU = 62.3 +/- 3.6 mg, P less than 0.001). Relative muscle interstitial fluid volume increased 107% in HU rats (35.5 +/- 2.8 microliters/100 mg wet mass) compared with the control value of 17.2 +/- 0.5 microliters/100 mg (P less than 0.001); however, absolute interstitial fluid volume (microliters) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757329 TI - Ibuprofen attenuates plasma tumor necrosis factor activity during sepsis-induced acute lung injury. AB - Plasma tumor necrosis factor (TNF) activity, cardiac index, extravascular lung water, systemic and pulmonary arterial pressures, pulmonary vascular resistance index, and arterial PO2 were monitored for 300 min in four groups of anesthetized pigs: saline-infused animals (n = 5), saline-infused animals given ibuprofen (12.5 mg/kg iv) at 0 and 120 min (n = 4), animals infused for 60 min with live Pseudomonas aeruginosa (Ps, 5 x 10(8) organisms/ml at 0.3 ml.20 kg-1.min-1, n = 6), and animals infused for 60 min with Ps plus ibuprofen administered at 0 and 120 min (n = 4). Infusion of Ps induced significant elevations (greater than 4 fold increase in units/ml of TNF by 60 min, P less than 0.05) in plasma TNF activity (L929 cytolysis assay) and alterations (P less than 0.05) in all hemodynamic and pulmonary parameters within 30-60 min. Ibuprofen administration in sepsis significantly decreased peak TNF activity by 2 units/ml and attenuated many of the physiological alterations due to sepsis. These results show that ibuprofen attenuates sepsis-induced injury and that alterations of acute septic insult are correlated with reduced plasma TNF activity in septic animals given ibuprofen. PMID- 1757330 TI - Glucoregulatory and hormonal responses to repeated bouts of intense exercise in normal male subjects. AB - Glucose turnover and its regulation were studied during and after two identical bouts of intense exhaustive exercise separated by 1 h to define differences in response. Six lean young postabsorptive male subjects exercised at approximately 100% maximal O2 uptake (3.7 +/- 0.3 l/min) for 13.0 +/- 0.7 min for the first (EX1) and 13.2 +/- 0.8 min for the second (EX2) bout. Plasma glucose increased during EX1 and peaked at 7.0 +/- 0.6 mmol/l in early recovery but to 5.8 +/- 0.5 mmol/l (P less than 0.05) after EX2, and both the hyperglycemic and the hyperinsulinemic responses were less after EX2 (P less than 0.015, analysis of variance). The hyperglycemia was due to lesser increments in glucose utilization (Rd) (3-fold resting) than glucose production (Ra) (7-fold) toward exhaustion and for 7 min of recovery. The rise in Rd was more rapid (P less than 0.05) and metabolic clearance rate was greater during (P = 0.015) and from 9 to 60 min after EX2, and Ra also remained higher during recovery (P less than 0.05). Marked and similar increments in plasma norepinephrine (18-fold) and epinephrine (14 fold) occurred with both bouts. Plasma glucagon increments were small and not different. Therefore, 1) more circulating glucose was used with EX2, 2) greater metabolic clearance rate during and after EX2 suggests local muscle adaptations due to EX1, and 3) significant correlations (P less than 0.002) between plasma norepinephrine and Ra (r = 0.82) and Ra - Rd (r = 0.52) and between epinephrine and Ra (r = 0.71) and Ra - Rd (r = 0.48) suggest a major regulatory role for the catecholamine responses. PMID- 1757331 TI - Blood rheology in acute mountain sickness and high-altitude pulmonary edema. AB - The role of blood rheology in the pathogenesis of acute mountain sickness and high-altitude pulmonary edema was investigated. Twenty-three volunteers, 12 with a history of high-altitude pulmonary edema, were studied at low altitude (490 m) and at 2 h and 18 h after arrival at 4,559 m. Eight subjects remained healthy, seven developed acute mountain sickness, and eight developed high-altitude pulmonary edema. Hematocrit, whole blood viscosity, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability (filtration) were measured. Plasma viscosity and erythrocyte deformability remained unaffected. The hematocrit level was lower 2 h after the arrival at high altitude and higher after 18 h compared with low altitude. The whole blood viscosity changed accordingly. The erythrocyte aggregation was about doubled 18 h after the arrival compared with low-altitude values, which reflects the acute phase reaction. There were, however, no significant differences in any rheological parameters between healthy individuals and subjects with acute mountain sickness or high-altitude pulmonary edema, either before or during the illness. We conclude that rheological abnormalities can be excluded as an initiating event in the development of acute mountain sickness and high-altitude pulmonary edema. PMID- 1757332 TI - Inspiratory timing of heart-lung transplant recipients during progressive hypercapnia. AB - The relationship between tidal volume (VT) and inspiratory duration (TI) displays biphasic characteristics during progressive hypercapnia in humans: an initial phase in which VT increases while TI remains constant (region I) and a subsequent phase with reciprocal decreases of TI as VT continues to increase (region II). Region II behavior is generally attributed, albeit inferentially, to lung volume mediated inflation inhibition (Breuer-Hering reflex). To investigate this phenomenon, we compared CO2 responses of 10 heart-lung transplant recipients (HL) with normal pulmonary function tests and 13 normal controls. Despite pulmonary denervation, the HL exhibited region II behavior identical to controls. In four additional HL with pulmonary restriction, there were comparative decreases of the region II slope (P less than 0.05), but the absolute VT where the phase change between regions occurred was indistinguishable from the other groups. We conclude that TI shortening in humans during progressive hypercapnia occurs in the absence of pulmonary reflexes. The consistency of the VT associated with phase changes, despite pulmonary denervation, suggests that the stimulus for this behavior is volume displacement of extra-pulmonary respiratory structures. PMID- 1757333 TI - Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits. AB - We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30-60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade. PMID- 1757334 TI - Site of action of calcium channel blockers in inhibiting endogenous pyrogen fever in rats. AB - We have demonstrated that the Ca2+ channel blocker verapamil, administered intravenously, exerts an antipyretic effect on the febrile responses of rats to intravenously injected endogenous pyrogen (EP). We have also shown that the same intravenous dose of verapamil is ineffective in blocking fevers induced by the microinjection of exogenous prostaglandin E (PGE) into the organum vasculosum laminae terminalis (OVLT) of rats. Experiments were conducted to determine whether the site of this verapamil antipyresis was in the OVLT itself. The febrile responses of six male Sprague-Dawley rats to EP were determined at thermoneutrality. Verapamil (10 micrograms/rat) was microinjected directly into the OVLT, and the febrile responses to the EP dose were redetermined 15-30 min later. In every case the EP fevers were attenuated after verapamil pretreatment. Intra-OVLT injections of verapamil alone were without effect on body temperature. When the same dose of verapamil was injected into the OVLT 15 min before the injection of PGE into the same site, it had no effect on the ensuing PGE-induced fever. In view of the fact that less than 1/250th of the effective systemic dose of verapamil, when injected into the OVLT, was equally effective in blocking the EP fevers, we conclude that verapamil acts within the OVLT to block fever rather than peripherally. Furthermore, because verapamil administered into the OVLT does not block PGE fevers, it is unlikely that PGE produces fever by acting as a Ca2+ ionophore on hypothalamic neurons. PMID- 1757335 TI - Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease. AB - To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757336 TI - Posterior cricoarytenoid activity and glottic size during hyperpnea in humans. AB - We measured the electromyographic activity of the posterior cricoarytenoid (PCA) muscle simultaneously with glottic width (dg) in five normal human subjects during hyperpnea induced by hypoxia (7% CO2 in N2) or hypercapnia (9% CO2 in 50% O2). The glottic aperture was measured during inspiration at the time corresponding to peak inspiratory PCA activity and during expiration at the time corresponding to the minimum tonic activity. During hyperpnea, peak and tonic PCA activity increased simultaneously with widening of the vocal cords in both phases of the respiratory cycle. The PCA activity during both inspiration and expiration showed a single curvilinear relationship with dg of the form dg = A - Be-k.PCA (where A, B, and k are constants) in three of the five subjects. At 50% of maximum PCA activity, dg already reached 95% of its maximum value, which was less than that recorded during a voluntary forced expiratory maneuver. The single curvilinear relationship between PCA activity and dg could be due to the length tension relationship of the PCA muscle and/or changes in its mechanical coupling, as well as simultaneous agonist and antagonist laryngeal muscle activity during progressive chemical stimulation. Also, further widening of the glottis during forced expiration suggests recruitment of additional muscles, e.g., the arytenoideus. PMID- 1757337 TI - Steady and oscillatory transnasal pressure-flow relationships in healthy adults. AB - The influence of flow characteristics and gas physical properties on nasal resistance (NR) is difficult to ascertain with traditional rhinomanometric methods because the respiratory airflows used in these methods are largely uncontrolled. As an alternative, we used a novel method of rhinomanometry in which an externally generated flow is passed through the nasal passage via a mouthpiece. The transnasal pressure-flow relationships for both quasi-steady and oscillating flows and with different gases were obtained in five healthy adults with this method. For quasi-steady nasal flows the dimensionless pressure losses were largely independent of physical properties of the gas and a function of the Reynolds number (Re) of the flow. Values of NR for quasi-steady flows were largely independent of flow direction for Re up to roughly 3,000 in all five subjects and for Re up to roughly 19,000 in two of the five subjects. Airway collapse occurred in two subjects at Re greater than 3,000, suggesting that the nonrigid segments of the nasal passage contribute to the intersubject variations in NR at high flow rates. Pressure losses associated with oscillating flows measured at frequencies between 1 and 16 Hz were similar to steady flow losses provided that Re was less than roughly 3,000. For Re greater than 3,000 the oscillating flow resistances were affected by the phasic redistribution of flow into compliant segments of the nasal passage. These results indicate that, for flow rates and harmonic frequencies associated with breathing at rest, the nasal passage behaves as a rigid rough-walled pipe in which pressure losses are largely determined by forces relating to viscous friction and convective accelerations. PMID- 1757338 TI - Oxygen cost and oxygen uptake dynamics and recovery with 1 min of exercise in children and adults. AB - To test the hypothesis that O2 uptake (VO2) dynamics are different in adults and children, we examined the response to and recovery from short bursts of exercise in 10 children (7-11 yr) and 13 adults (26-42 yr). Each subject performed 1 min of cycle ergometer exercise at 50% of the anaerobic threshold (AT), 80% AT, and 50% of the difference between the AT and the maximal O2 uptake (VO2max) and 100 and 125% VO2max. Gas exchange was measured breath by breath. The cumulative O2 cost [the integral of VO2 (over baseline) through exercise and 10 min of recovery (ml O2/J)] was independent of work intensity in both children and adults. In above-AT exercise, O2 cost was significantly higher in children [0.25 +/- 0.05 (SD) ml/J] than in adults (0.18 +/- 0.02 ml/J, P less than 0.01). Recovery dynamics of VO2 in above-AT exercise [measured as the time constant (tau VO2) of the best-fit single exponential] were independent of work intensity in children and adults. Recovery tau VO2 was the same in both groups except at 125% VO2max, where tau VO2 was significantly smaller in children (35.5 +/- 5.9 s) than in adults (46.3 +/- 4 s, P less than 0.001). VO2 responses (i.e., time course, kinetics) to short bursts of exercise are, surprisingly, largely independent of work rate (power output) in both adults and children. In children, certain features of the VO2 response to high-intensity exercise are, to a small but significant degree, different from those in adults, indicating an underlying process of physiological maturation. PMID- 1757339 TI - Relationship between exercise-induced muscle damage and enzyme release in rats. AB - The relationship between the amount of exercise-induced muscle damage and the release of creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LD) was studied. Gender differences in enzyme release and histological damage were also studied. Serial pre- and postexercise blood samples were drawn from untrained male and female catheterized Wistar rats that ran 1.5 or 2.5 h on a treadmill (incline 10 degrees). Three days postexercise, muscle damage was quantified morphometrically in five different hindlimb and forearm muscles. The 1.5 and 2.5 h of exercise elicited histological damage only in the soleus muscle. Significant plasma CK, AST, and LD elevations were found immediately postexercise both in male and female rats. However, the enzyme release was significantly greater in males than in females. Part of this could be explained by differences in clearance rates between males and females. No gender difference in amount of histological damage was found. The actual volume of histological muscle damage was significantly less than the calculated muscle damage based on enzyme release. An increase in the exercise duration from 1.5 to 2.5 h resulted in a disproportional increase in both histological muscle damage and muscle enzyme release. From the present study it is concluded that muscle enzyme release is not clearly reflected in histological muscle damage. PMID- 1757340 TI - Oxygen radical mechanisms of brain injury following ischemia and reperfusion. AB - This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted. PMID- 1757341 TI - Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure. AB - Alterations in regional cerebral blood flow (rCBF) and percent perfused capillaries (indicative of functional intercapillary distance) were determined in conscious male Long-Evans rats after reducing their blood O2-carrying capacity by exposing them to 1% CO for 12 min. rCBF was determined by the iodoantipyrine method. rCBF increased from a mean of 106 +/- 8 (SE) ml.min-1.100 g-1 before CO exposure to 173 +/- 14 ml.min-1.100 g-1 after CO exposure. There was a greater flow increase (126%) in the cerebral cortex than in the lower brain stem [pons (45%), medulla (39%)]. Presence of fluorescein isothiocyanate-labeled dextran identified the perfused capillaries before and after CO exposure. The volume fraction (Vv) and number/mm2 (Na) of all capillaries (perfused and nonperfused) in a given area of brain were determined after staining for alkaline phosphatase. The percent Vv and percent Na of perfused capillaries increased uniformly (from approximately 50% to approximately 80%) in all parts of the brain after CO exposure. In the presence of tissue hypoxia with undiminished plasma PO2, the brain vasculature allowed greater flow of blood while the microvasculature adjusted to reduce the diffusion distance for O2. PMID- 1757342 TI - Ventilation during early and late rapid-eye-movement sleep in normal humans. AB - Because successive rapid-eye-movement (REM) sleep periods in the night are longer in duration and have more phasic events, ventilation during late REM sleep might be more affected than in earlier episodes. Despite the increase in eye movement density (EMD) in late REM sleep, average minute ventilation was, however, not reduced compared with that in early REM sleep. Decreases in rib cage motion (mean inspiratory flow of the rib cage) in association with increasing EMD were offset by increments in respiratory frequency. Apart from expiratory time, there were no significant changes in the slopes of the relationships between EMD and specific ventilatory components, from early to late REM sleep periods. However, there was an increase in the number of episodes when ventilation was reduced during late REM sleep. Changes in ventilatory pattern during late REM sleep are due to changes in the underlying nature of REM sleep. The ventilatory response during eye movements is, however, subject specific. Some subjects exhibit large decrements in mean inspiratory flow of the rib cage and increments in respiratory frequency during bursts of eye movement, whereas other individuals demonstrate only small changes in these ventilatory parameters. PMID- 1757343 TI - Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes. AB - This study evaluated the ability of aerosol-derived lung morphometry to noninvasively probe airway and acinar dimensions. Effective air-space diameters (EAD) were calculated from the time-dependent gravitational losses of 1-microns particles from inhaled aerosol boluses during breath holding. In 17 males [33 +/- 7 (SD) yr] the relationship between EAD and volumetric penetration of the bolus into the lungs (Vp) could be expressed by the linear power-law function, log (EAD) alpha beta log (Vp). Our EAD values were consistent with Weibel's symmetric lung model A for small airways and more distal air spaces. As lung volume increased from 57 to 87% of total lung capacity (TLC), EAD at Vp of 160 and 550 cm3 increased 70 and 41%, respectively. At 57% TLC, log (EAD) at 160 cm3 was significantly correlated with airway resistance (r = -0.57, P less than 0.0204) but not with forced expired flow between 25 and 75% of vital capacity. Log (EAD) at 400 cm3 was correlated with deposition of 1-micron particles (r = -0.73, P less than 0.0009). We conclude that aerosol-derived lung morphometry is a responsive noninvasive probe of peripheral air-space diameters. PMID- 1757344 TI - Effect of oxygenation on breath-by-breath response of the genioglossus muscle during occlusion. AB - We investigated the effect of different levels of O2 tension (hypoxia, normoxia, and hyperoxia) on the breath-by-breath onset and peak electromyographic (EMG) activity of the genioglossus (GG) muscle during a five-breath end-expiratory tracheal occlusion of 20- to 30-s duration. GG and diaphragmatic (DIA) EMG activity were measured with needle electrodes in eight anesthetized tracheotomized adult cats. In response to occlusion, the increase in the number of animals with GG EMG activity was different during hypoxia, normoxia, and hyperoxia (P = 0.003, Friedman). During hypoxia, eight of eight of the animals had GG EMG activity by the third occluded effort. In contrast, during normoxia, only four of eight and, during hyperoxia, only three of eight animals had GG EMG activity throughout the entire five-breath occlusion. Similarly, at release of the occlusion, more animals had persistent GG EMG activity on the postocclusion breaths during hypoxia than during normoxia or hyperoxia. Breath-by-breath augmentation of peak amplitude of the GG and DIA EMGs on each occluded effort was accentuated during hypoxia (P less than 0.01) and abolished during hyperoxia (P = 0.10). These results suggest that hypoxemia is a major determinant of the rapidity of onset, magnitude, and sustained activity of upper airway muscles during airway occlusion. PMID- 1757345 TI - Effects of load on oxygen intake in trained boys and men during treadmill running. AB - This investigation examines the effects of vertical and horizontal loading on the O2 intake (VO2) response of children (n = 8) and adults (n = 8) to treadmill running. In unloaded running, the children required a significantly greater VO2 (P less than 0.001) than the adults [mean difference 7 ml.kg-1.min-1 (18.5%)]. There was no significant difference in the VO2 response of the children and the adults to either vertical or horizontal loading. Vertical loading with 5 and 10% of body mass did not produce a significant increase in the VO2 response of either group. In contrast, horizontal loading produced a significant increase (P less than 0.001) in both groups. The consistent response to the two forms of loading suggests that there is no difference between children and adults in the apparent efficiency of running with an external load. Stride frequency showed a significant increase with vertical loading (P less than 0.001) and a significant decrease with horizontal loading (P less than 0.001) in both groups. PMID- 1757346 TI - Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans. AB - Rates of performing work that engender a sustained lactic acidosis evidence a slow component of pulmonary O2 uptake (VO2) kinetics. This slow component delays or obviates the attainment of a stable VO2 and elevates VO2 above that predicted from considerations of work rate. The mechanistic basis for this slow component is obscure. Competing hypotheses depend on its origin within either the exercising limbs or the rest of the body. To resolve this question, six healthy males performed light nonfatiguing [approximately 50% maximal O2 uptake (VO2max)] and severe fatiguing cycle ergometry, and simultaneous measurements were made of pulmonary VO2 and leg blood flow by thermodilution. Blood was sampled 1) from the femoral vein for O2 and CO2 pressures and O2 content, lactate, pH, epinephrine, norepinephrine, and potassium concentrations, and temperature and 2) from the radial artery for O2 and CO2 pressures, O2 content, lactate concentration, and pH. Two-leg VO2 was thus calculated as the product of 2 X blood flow and arteriovenous O2 difference. Blood pressure was measured in the radial artery and femoral vein. During light exercise, both pulmonary and leg VO2 remained stable from minute 3 to the end of exercise (26 min). In contrast, during severe exercise [295 +/- 10 (SE) W], pulmonary VO2 increased 19.8 +/- 2.4% (P less than 0.05) from minute 3 to fatigue (occurring on average at 20.8 min). Over the same period, leg VO2 increased by 24.2 +/- 5.2% (P less than 0.05). Increases of leg and pulmonary VO2 were highly correlated (r = 0.911), and augmented leg VO2 could account for 86% of the rise in pulmonary VO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757347 TI - Ventilatory effects and interactions with change in PaO2 in awake goats. AB - We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner. PMID- 1757348 TI - Nebulized vs. instilled exogenous surfactant in an adult lung injury model. AB - Three days after subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) to induce lung injury, adult rabbits were mechanically ventilated and lung function was evaluated. Each animal then received either nebulized Survanta (Neb Surv), nebulized saline (Neb Saline), nebulized gas alone (Neb Gas), or tracheally instilled Survanta (Inst Surv). The ventilation efficiency index (VEI) value increased significantly compared with pretreatment values (P less than 0.01) over a 3-h treatment period for the Neb Surv animals, whereas VEI values for the other three groups decreased after treatment (P less than 0.05). Arterial PO2-to fraction of inspired O2 ratios and dynamic compliance values significantly decreased after treatment for the Inst Surv group (P less than 0.05). Pressure volume curves demonstrated a significantly greater volume at maximal pressure for the Neb Surv group compared with each of the other groups studied (P less than 0.01). The calculated quantity of surfactant recovered in lung tissue for the Neb Surv group was only 4.9 +/- 1.0 mg lipid/kg compared with 100 mg lipid/kg delivered to the Inst Surv group. Surfactant administered as an aerosol resulted in modest physiological improvements in this model of lung injury and was superior to the tracheal instillation technique. PMID- 1757349 TI - Effect of aging on human adductor pollicis muscle function. AB - The effect of aging on the voluntary and electrically evoked contractile properties of the human adductor pollicis muscle was investigated in 70 healthy male subjects aged 20-91 yr, 10 subjects for each decade. Maximum isometric voluntary force declined significantly (range of P values less than 0.001-0.05) after the age of 59 yr, dropping by the eighth decade to 57.6% of the level recorded in the second decade. A significant shift (P range less than 0.001-0.05) to the left of the frequency-force curve after ulnar nerve supramaximal stimulation at 1, 10, 20, 30, and 50 Hz was observed in the most elderly group (greater than 80 yr) compared with the youngest group (20-29 yr). Maximum relaxation rate dropped by 48.7% from the second to the eighth decade. The decrease became significant (P range less than 0.05-0.001) with the sixth decade. Isometric endurance, evaluated during 30 s of stimulation at 30 Hz, showed a linear (P less than 0.001) increase with age. Aged muscle is thus weaker, slower, and tetanized at lower fusion frequencies but, paradoxically, more resistant to static fatigue. PMID- 1757350 TI - Changes in tracheal mucosal thickness and blood flow in sheep. AB - Airway narrowing may be produced by increasing the blood volume of the airway mucosa. Here changes in tracheal mucosal thickness (MTtr) were measured in 10 anesthetized sheep. Arteries to the cervical trachea were isolated, and blood flow (Qtr) was measured with an electromagnetic flow probe. Simultaneous changes in MTtr were measured with a mechanical probe over a fixed cartilage. Arterial injections of phenylephrine produced dose-related falls in Qtr and MTtr with a maximum peak fall in MTtr of -104 +/- 18 (SE) microns. Methacholine, bradykinin, albuterol, and histamine produced dose-related increases in Qtr. The largest peak increase in MTtr of 308 +/- 121 microns was seen with bradykinin. For methacholine, albuterol, and histamine the largest increases in MTtr were 154 +/- 47, 45 +/- 10, and 153 +/- 31 microns, respectively. The increases in MTtr were not always closely dose related. The peak changes in MTtr occurred substantially later than those in Qtr for all the drugs and up to 120 s later for methacholine and bradykinin. Generally, changes in MTtr and Qtr persisted for less than 10 min; at the higher doses of bradykinin increases in MTtr lasted for up to 15 min. Changes in MTtr were most closely associated in time with changes in Qtr for the vasoconstrictor phenylephrine. These changes in MTtr would alter airway resistance little in the normal trachea and by substantially more in smaller airways such as the bronchi or in the narrowed trachea. Changes in mucosal thickness may be due not only to changes in tracheal blood volume but may also reflect the effects of tissue edema and mucus secretion. PMID- 1757351 TI - Core temperature "null zone". AB - An experimental protocol was designed to investigate whether human core temperature is regulated at a "set point" or whether there is a neutral zone between the core thresholds for shivering thermogenesis and sweating. Nine male subjects exercised on an underwater cycle ergometer at a work rate equivalent to 50% of their maximum work rate. Throughout an initial 2-min rest period, the 20 min exercise protocol, and the 100-min recovery period, subjects remained immersed to the chin in water maintained at 28 degrees C. On completion of the exercise, the rate of forehead sweating (Esw) decayed from a mean peak value of 7.7 +/- 4.2 (SD) to 0.6 +/- 0.3 g.m-2.min-1, which corresponds to the rate of passive transpiration, at core temperatures of 37.42 +/- 0.29 and 37.39 +/- 0.48 degrees C, as measured in the esophagus (Tes) and rectum (Tre), respectively. Oxygen uptake (VO2) decreased rapidly from an exercising level of 2.11 +/- 0.25 to 0.46 +/- 0.09 l/min within 4 min of the recovery period. Thereafter, VO2 remained stable for approximately 20 min, eventually increased with progressive cooling of the core region, and was elevated above the median resting values determined between 15 and 20 min at Tes = 36.84 +/- 0.38 degrees C and Tre = 36.80 +/- 0.39 degrees C. These results indicate that the core temperatures at which sweating ceases and shivering commences are significantly different (P less than 0.001) regardless of whether core temperature is measured within the esophagus or rectum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757352 TI - Effect of catheter size on pressures recorded in small pulmonary veins in dog lung. AB - Controversy continues about the contribution of the veins to pulmonary vascular resistance. From data obtained in studies using intravascular catheters, it appears that a major fraction (up to 44%) of the total pulmonary vascular pressure drop resides in larger (greater than 1.0 mm diam) veins, whereas micropuncture data and various models give much less pressure drop. Theoretically, artifactual pressure drops can be obtained if an intravascular catheter partly obstructs the vessel. We made measurements of pressure in the same lung vein with two different-sized catheters (1.2 and 0.6 mm OD, respectively). In paired experiments the larger catheter always measured a higher pressure than the smaller one, except close to the large lobar vein outlet. In some of the experiments we measured the diameter of the vessel containing the indwelling catheter by freezing the lung and then serial-sectioned the frozen lung. From these data we could infer that the range of vein diameter in the which the smaller catheter measured a lower pressure was 1.5-4 mm. We conclude that the larger catheter overestimated the pressure because of greater obstruction. The pressures obtained with the smaller catheter suggest that little (less than 10%) of the total pulmonary vascular resistance resides in veins larger than approximately 1 mm diam under zone 3 baseline conditions. PMID- 1757353 TI - Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat. AB - Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1-14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757354 TI - Thiol modification in H2O2- and thromboxane-induced vaso- and bronchoconstriction in rat perfused lung. AB - Hydrogen peroxide (H2O2), arachidonic acid (AA), and U-44069, a thromboxane analogue, all induced vaso- and bronchoconstriction in the isolated perfused rat lung. The role of protein sulfhydryl modifications in these processes was investigated. The thiol oxidizing agent diamide inhibited both vaso- and bronchoconstriction induced by H2O2, AA, or U-44069. Diamide had only a marginal effect on glutathione and protein thiol levels and no effect on lung mechanics. The diamide inhibition was reversible, and H2O2-induced vaso- and bronchoconstriction was almost maximal after 10 min of perfusion with buffer. The recovery was more rapid if dithiothreitol, a thiol reducing agent, was used in the buffer. H2O2- and AA-induced vaso- and bronchoconstriction is caused by thromboxane release. Diamide did not influence H2O2- or AA-dependent thromboxane formation, indicating that neither AA release nor AA metabolism to thromboxane is sensitive to thiol oxidation. Thus our results indicate that the site of diamide induced thiol oxidation is the thromboxane receptor or its signal transduction. PMID- 1757355 TI - Site of action of hypertonic saline in the canine lung. AB - The site of action of inhaled hypertonic saline was determined in 8- to 10-wk-old puppies by combining measurements of respiratory mechanics, made during mechanical ventilation and after midexpiratory flow interruptions, with direct measurements of alveolar pressure. Under both control conditions and after inhalation of 10% saline, we were able to partition lung mechanics into components representing the airways and tissue viscoelastic properties. Hypertonic saline challenge altered lung mechanics by increasing airway resistance and did not have any effect on elastic or viscoelastic properties of the lung. PMID- 1757356 TI - Effects of muscle glycogen and plasma FFA availability on human metabolic responses in cold water. AB - The purpose of this study was to investigate whether simultaneous alterations in the availability of plasma free fatty acids and muscle glycogen would impair the maintenance of thermal balance during cold water immersion in humans. Eight seminude subjects were immersed on two occasions in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each immersion followed 2.5 days of a specific dietary and exercise regimen designed to elicit low (LOW) or high glycogen levels (HIGH) in large skeletal muscle groups. Nicotinic acid (1.6 mg/kg) was administered for 2 h before and during immersion to inhibit white adipose tissue lipolysis. Biopsies from the vastus lateralis showed that the glycogen concentration before the immersion was significantly lower in LOW than in HIGH (223 +/- 19 vs. 473 +/- 24 mmol glucose units/kg dry muscle). However, the mean rates of glycogen utilization were not significantly different between trials (LOW 0.62 +/- 0.14 vs. HIGH 0.88 +/- 0.15 mmol glucose units.kg-1.min-1). Nicotinic acid dramatically reduced plasma free fatty acid levels in both trials, averaging 127 +/- 21 mumol/l immediately before the immersion. Cold water immersion did not significantly alter those levels. Plasma glucose levels were significantly reduced after cold water immersion to a similar extent in both trials (18 +/- 4%). Mean respiratory exchange ratio at rest and during immersion was greater in HIGH than LOW, whereas there were no intertrial differences in O2 uptake. The calculated average metabolic heat production during immersion tended to be lower (P = 0.054) in LOW than in HIGH (15.3 +/- 1.9 vs. 17.5 +/- 1.9 kJ/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757357 TI - Effect of geniohyoid and sternohyoid muscle contraction on upper airway resistance in the cat. AB - Previous investigators (van Lunteren et al. J. Appl. Physiol. 62: 582-590, 1987) have suggested that the geniohyoid and sternohyoid muscles may act as upper airway dilators in the cat. To investigate the effect of geniohyoid and sternohyoid contraction on inspiratory upper airway resistance (UAR), we studied five adult male cats anesthetized with ketamine and xylazine during spontaneous room-air breathing. Inspiratory nasal airflow was measured by sealing the lips and constructing a nose mask. Supraglottic pressure was measured using a transpharyngeal catheter placed above the larynx. Mask pressure was measured using a separate catheter. Geniohyoid and sternohyoid lengths were determined by sonomicrometry. Geniohyoid and sternohyoid contraction was stimulated by direct muscle electrical stimulation with implanted wire electrodes. Mean inspiratory UAR was determined for spontaneous breaths under three conditions: 1) baseline (no muscle stimulation), 2) geniohyoid contraction alone, and 3) sternohyoid contraction alone. Geniohyoid contraction alone produced no significant reduction in inspiratory UAR [unstimulated, 17.75 +/- 0.86 (SE) cmH2O.l-1.s; geniohyoid contraction, 19.24 +/- 1.10]. Sternohyoid contraction alone also produced no significant reduction in inspiratory UAR (unstimulated, 15.74 +/- 0.92 cmH2O.l 1.s; sternohyoid contraction, 14.78 +/- 0.78). Simultaneous contraction of the geniohyoid and sternohyoid muscles over a wide range of muscle lengths produced no consistent change in inspiratory UAR. The geniohyoid and sternohyoid muscles do not appear to function consistently as upper airway dilator muscles when UAR is used as an index of upper airway patency in the cat. PMID- 1757358 TI - Effects of hypoxia and cold acclimation on thermoregulation in the rat. AB - The effects of hypoxia (inspired O2 fraction = 0.12) on thermoregulation and on the different sources of thermogenesis were studied in rats before and after periods of 1-4 wk of cold acclimation. Measurements of metabolic rate (VO2) and body temperature (Tb) were made at 5-min intervals, and shivering activity was recorded continuously in groups of rats subjected to three protocols. In protocol 1, rats were exposed to normoxia to an ambient temperature (Ta) of 5 degrees C for 2 h. In protocol 2, at Ta of 5 degrees C, rats were exposed for 30 min to normoxia, then for 45 min to hypoxia, and finally for 30 min to normoxia. In protocol 3, in the non-cold-acclimated (NCA) rats, Ta was decreased from 30 to 5 degrees C in steps of 5 degrees C and of 30-min duration while in cold-acclimated (CA) rats at 5 degrees C for 4-wk, Ta was increased from 5 to 30 degrees C in steps of 5 degrees C and of 30-min duration. Recordings were made in normoxia and in hypoxia on different days in the same animals. The results showed that 1) in NCA rats, cold exposure in normoxia induced increases in VO2 and shivering that were proportional to the decrease in Ta; 2) in CA rats in normoxia, for a given Ta, VO2 and Tb were higher than in NCA rats, whereas shivering was generally lower; and 3) in both NCA and CA rats, hypoxia induced a transient decrease in shivering and a sustained decrease in nonshivering thermogenesis associated with a marked decrease in Tb that was about the same in NCA and CA rats. We speculate that hypoxia acts on Tb control to produce a general inhibition of thermogenesis. Nonshivering thermogenesis is markedly sensitive to hypoxia, especially demonstrable in CA rats; a recovery or even an increase in shivering can compensate for the decrease in nonshivering thermogenesis. PMID- 1757359 TI - Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats. AB - Kainic acid (KA) injections into the retrotrapezoid nucleus (RTN) of anesthetized deafferented cats profoundly decreased phrenic activity (PA) and CO2 sensitivity (J. Appl. Physiol. 68: 1157-1166, 1990). In this study small electrolytic lesions of the RTN produced the same results, indicating that the KA destroyed cells. We then asked whether anesthetic depression or the absence of peripheral chemoreceptors could explain the degree of respiratory depression observed. In decerebrate cats electrolytic lesions of the RTN resulted in a decrease in PA similar to that seen under anesthesia. CO2 sensitivity was decreased by RTN lesions that extended into the caudal RTN but less so than under anesthesia. KA injections resulted in an initial increase in PA followed by a continuous decrease, a pattern similar to that seen under anesthesia but with a slower time course. CO2 sensitivity was essentially absent. Peripheral chemodenervation produced a small further decrease in PA and a downward shift of the CO2 response without change in slope. Blood pressure was unaffected by RTN lesions but was decreased by more-caudal lesions without respiratory effects. The RTN appears to be necessary for the maintenance of eupneic phrenic activity and CO2 sensitivity even in decerebrate cats with intact peripheral chemoreceptors. PMID- 1757360 TI - Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep. AB - We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 micrograms/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 micrograms.kg-1.min-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 +/- 0.7 to 8.9 +/- 0.51.min-1.m-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7. Other indexes of the LV contractility (+dP/dtmax) were also reduced. OKY 046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also attenuated the increased lung lymph flow changes seen with LPS. PMID- 1757361 TI - Effect of hypovolemia on forearm vascular resistance control during exercise in the heat. AB - To determine the influence of hypovolemia on the control of forearm vascular resistance (FVR) during dynamic exercise, we studied five physically active men during 60 min of supine cycle ergometer exercise bouts at 35 degrees C in control (normovolemic) and hypovolemic conditions. Hypovolemia was achieved by 3 days of diuretic administration and resulted in an average decrease in plasma volume of 15.9%. Relative to normovolemia, hypovolemia caused an attenuation of the progressive rise in forearm blood flow (P less than 0.05) and an increase in heart rate (P less than 0.05) during exercise. Because mean arterial blood pressure during hypovolemic exercise was well maintained, the attenuation of forearm blood flow was due entirely to a relative increase in FVR. At the onset of dynamic exercise, FVR was increased significantly in control and hypovolemic conditions by 13.2 and 27.1 units, respectively. The increase in FVR was significantly different between control and hypovolemic conditions as well. We attributed the increased vasoconstrictor bias during hypovolemia to cardiopulmonary baroreceptor unloading and/or an increased sensitivity to cardiopulmonary baroreceptor unloading. We concluded that reduced blood flow to the periphery during exercise in the hypovolemic condition was caused entirely by an increase in vascular resistance, thereby preserving arterial blood pressure and adequate perfusion to the organs requiring increased flow. PMID- 1757362 TI - Effects of high-intensity sprint training on skeletal muscle blood flow in rats. AB - The regional blood flow response (via radioactive microspheres) was determined for female rats after 6 wk of high-intensity sprint training (HIST) or limited cage activity as the animals exercised at work loads that would elicit maximal O2 uptake. Blood flow to the different organs of the abdominal region was greatly reduced during maximal exercise conditions, and the magnitude of the reduction appeared to be similar for both the HIST group of rats and their sedentary (SED) control counterparts. Of the 20 different hindlimb muscles examined in the present study, blood flow to the soleus, plantaris, gastrocnemius, flexor hallicus longus, vastus lateralis, rectus femoris, biceps femoris, and adductor magnus and brevis muscles was significantly greater (P less than 0.05) in the HIST rats during maximal exercise conditions than in the SED control rats. Correspondingly, blood flow to the total hindlimb during maximal exercise was also significantly greater in the HIST rats than in the SED control rats [240 +/- 18 vs. 192 +/- 15 (SE) ml.min-1.100 g-1]. These results support the contention that the increase in maximal cardiac output that is produced by HIST in the rat is primarily directed toward the working skeletal muscle and not toward the organs found in the abdominal region. We conclude from these experiments that HIST will produce significant adaptations in central cardiac function and skeletal muscle blood flow in the rat. PMID- 1757363 TI - Analysis of pulmonary microvascular permeability after smoke inhalation. AB - We estimated the reflection (sigma) and filtration coefficients (Kf) in a chronic sheep lung lymphatic preparation after smoke inhalation. Group I (n = 7) sheep were insufflated with cotton smoke and group II animals (n = 5) with room air. After inhalation injury, the lung lymph flow increased nearly four times the baseline value by 24 h after injury. There was a concomitant reduction of sigma (0.81 +/- 0.02 to 0.64 +/- 0.02) and elevation of Kf (0.020 +/- 0.002 to 0.042 +/ 0.009 ml.min-1.mmHg-1); pulmonary capillary pressure was also elevated (13 +/- 1 to 17 +/- 1 mmHg). By 48 h postinjury, sigma and Kf returned toward baseline but pulmonary capillary pressure was still elevated. We determined that 34% of the increase in capillary filtration was attributable to increased capillary pressure and 66% to increased permeability 24 h after inhalation, but 48 h after injury, 75% of the increase in capillary filtration was attributable to increased capillary pressure and 25% to increased permeability. We conclude that the lung edema formation following smoke inhalation is the result of marked increases in both capillary pressure and permeability. PMID- 1757364 TI - Heparin reversal by protamine in humans--complement, prostaglandins, blood cells, and hemodynamics. AB - Fourteen noncardiac surgical patients received heparin (10,000 IU), which was neutralized by 100 mg protamine injected within 2 min during steady-state anesthesia. After protamine application, plasma complement C3a, thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and KH2PGF2 alpha increased significantly, whereas prostacyclin (6-keto-PGF2 alpha) levels did not change. This mediator response was associated with transient leukopenia and thrombocytopenia. Arterial pressure, pulmonary arterial pressure, and transpulmonary pressure gradient increased significantly. Heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial PO2 remained constant. Positive correlations of plasma C3a were observed with pulmonary leukosequestration and plasma TxB2. Inverse correlations of C3a were noted with the counts of leukocytes and of platelets. A positive correlation was found between TxB2 and pulmonary arterial pressure. Our results indicate that marked activation of the complement system and the cyclooxygenase pathway is common after heparin reversal by protamine in anesthetized patients. This is in contrast to previous human studies performed after cardiopulmonary bypass but agrees well with results obtained in animal experiments. The mediator response in our patients, however, was not accompanied by hemodynamic instability, suggesting appropriate compensatory mechanisms. PMID- 1757365 TI - Acoustic myography for investigating human skeletal muscle fatigue. AB - Sounds produced during voluntary isometric contractions of the quadriceps muscle were studied by acoustic myography (AMG) in five healthy adults. With the subject seated, isometric force, surface electromyography (EMG), and AMG were recorded over rectus femoris, and the EMG and AMG signals were integrated (IEMG and IAMG). Contractions lasting 5 s each were performed at 10, 25, 50, 60, 75, and 100% of maximum voluntary contraction (MVC) force. Fatigue was then induced by repeated voluntary contractions (10 s on, 10 s off) at 75% MVC until only 40% MVC could be sustained. After 15 min of rest, the different force levels were again tested in relation to the fresh MVC. Both before and after fatiguing activity the relationships between force and IEMG [r = 0.99 +/- 0.01 (SD), n = 10] and force and IAMG (r = 0.98 +/- 0.02) were linear. After activity, however, the slopes of the regression lines for force and IEMG increased (P less than 0.01) but those for force and IAMG remained the same (P greater than 0.05). The present results clarify the relationship between AMG and isometric force in fatigued muscle without the problem of fatigue-induced tremor, which hampered previous studies of prolonged activity. This study contributes to the validation of AMG and shows that it is a potentially useful method for noninvasive assessment of force production and fatigue. Further studies to establish the origin of AMG activity are required before AMG can be accepted for use in neuromuscular physiology or rehabilitation. PMID- 1757366 TI - Plasma catecholamine and lactate response during graded exercise with varied glycogen conditions. AB - The relationships between the lactate threshold (TLa), plasma catecholamines, and ventilatory threshold (TVE) were examined under normal and glycogen-depleted conditions. Nine male subjects performed a graded exercise test on a bicycle ergometer in a normal glycogen (NG) state and in a glycogen-depleted (GD) state to determine if manipulation of muscle glycogen content would affect their ventilatory, lactate, and catecholamine responses. High correlations were found between plasma lactate and the two catecholamines, epinephrine (r = 0.964) and norepinephrine (r = 0.965) under both conditions. The GD protocol resulted in a shift in the TLa to a later work rate; inflections in epinephrine and norepinephrine shifted in a coordinated manner. TVE and TLa occurred at similar work loads under NG conditions [67.2 +/- 1.5 and 65.6 +/- 2.3% maximal oxygen consumption (VO2max), respectively], but TLa occurred at a later work load (75.3 +/- 1.9% VO2max) compared with TVE (68.3 +/- 1.6% VO2max) under GD conditions. These results suggest a causal relationship between plasma lactate and epinephrine during a graded exercise test under the glycogen conditions studied. Although an association existed between ventilation and lactate, this relationship was not as strong. PMID- 1757367 TI - Role of the epithelium in airway smooth muscle responses to relaxant agonists. AB - We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances. PMID- 1757368 TI - Effects of flow on recombinant tissue plasminogen activator-induced pulmonary thrombolysis. AB - We employed a canine model of pulmonary embolism induced by injection of radioactive blood clots to investigate effects of changes in cardiac output (CO) on recombinant tissue plasminogen activator- (rtPA) induced pulmonary thrombolysis. Rate and extent of thrombolysis were assessed with a gamma camera. Eighteen dogs were studied. Emboli increased mean pulmonary arterial pressure and decreased CO from 2.6 to 1.9 l/min (P less than 0.001). Subsequently, dogs were randomly divided into three groups: group 1 received 0.5 mg/kg of rtPA over 30 min; 30 min before the same dose regimen of rtPA, in the six group 2 dogs, mean CO was increased to approximately 3.25 l/min by opening one systemic arteriovenous fistula; in the six group 3 dogs, before rtPA, mean CO was increased to approximately 4.5 l/min by opening two or three fistulas. After embolization, CO remained low in group 1; the mean 2-h time-averaged CO was 1.8 l/min. CO was much higher in groups 2 and 3 (3.3 and 4.6 l/min, respectively; both P less than 0.001 compared with group 1; and P less than 0.001, group 2 vs. group 3). Compared with group 1, corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in flow per se augments rtPA-induced pulmonary thrombolysis. Also, because thrombolysis was similar between groups 2 and 3, these results define an upper limit to the flow-thrombolytic relationship with rtPA. PMID- 1757369 TI - Cerebral metabolic and pressure-flow responses during sustained hypoxia in awake sheep. AB - Conscious sheep (n = 6), exposed to 3.5 h of normobaric hypoxia (arterial PO2 = 40 Torr) while allowed varying arterial PCO2, showed striking early increments of cerebral blood flow (CBF; +200-250%, by radiolabeled microspheres) and decrements of cerebral vascular resistance (CVR) in association with an early temporary elevation of cerebral O2 consumption (CMRO2; +25-60%). After 2 h, CMRO2 returned to normoxic levels, while CBF declined to a lower but still elevated level (+150%). CBF/CMRO2 increased twofold, while cerebral fractional extraction of O2 was unchanged. Mean arterial pressure was unchanged, but cerebral venous pressure rose (+11 mmHg) in a stable fashion such that cerebral perfusion pressure declined by 13%. Cerebral venous hematocrit and hemoglobin concentration were both elevated (+2.2-2.7% Hct units; +1.0-1.3 g/dl, respectively) above the corresponding arterial values between 150 and 210 min of hypoxia, suggesting venous hemoconcentration in possible association with a transcapillary fluid shift. CBF, and especially CVR, were well correlated with arterial O2 content. PMID- 1757370 TI - Pregnancy-induced changes in the maximal physiological responses during swimming. AB - The effect of pregnancy on peak O2 uptake (VO2 peak) during tethered swimming was evaluated in 10 women during their 25th and 35th wk of pregnancy, as well as 9-11 wk postpartum. The swim results were compared with cycle ergometry results obtained at similar times. The results indicated that exercise-induced maximal heart rates remained the same and were similar for the swim and cycle trials, approximately 184 +/- 4 beats/min. Cycling VO2 peak was not affected by pregnancy, averaging 1.94 +/- 0.11 l/min. Postpartum swim VO2 peak was similar to the cycle results; however, during pregnancy it was significantly lower than cycling VO2 peak (P less than 0.05; postpartum, 1.78 +/- 0.14 l/min; 25th wk, 1.64 +/- 0.12; 35th wk, 1.48 +/- 0.11). Hemoglobin concentrations and hematocrits were lower during pregnancy; however, changes in plasma volume (based on hematocrit and hemoglobin) were found to be significantly greater during cycling than during swimming and also greater during pregnancy for both modes of exercise. It was concluded that, unlike cycling, the VO2 peak of pregnant women during swimming is reduced. This reduction in VO2 peak was associated with a decreased peak ventilation (r = 0.864) but was not correlated to exercise-induced hemoconcentration (r = -0.29). Furthermore, pregnancy results in a greater-than normal exercise-induced hemoconcentration, which may be related to pregnancy induced changes in capillary dynamics. PMID- 1757371 TI - Effects of perfusate buffer capacity on capillary CO2-HCO3(-)-H+ reactions: theory. AB - The importance of perfusate nonbicarbonate buffer capacity (beta nonHCO3) to intracapillary CO2-HCO3(-)-H+ reactions was assessed by theoretical analysis of CO2 exchange in saline-perfused pulmonary capillaries. Time courses for perfusate PCO2, [HCO3-], and [H+] were computed for capillaries containing different activities of luminal vascular carbonic anhydrase and different amounts of perfusate nonbicarbonate buffers. Mobilization of perfusate HCO3- toward CO2 during capillary transit is determined by the availability of HCO3- and H+. A supply of protons from the nonbicarbonate buffer pool is necessary to maintain a high rate of HCO3- dehydration. The analyses indicate that beta nonHCO3 has marked nonlinear effects on transcapillary CO2 exchange and intravascular pH equilibration. These nonlinear effects differ from those previously computed for CO2 reactions in an open system because the present model system consists of a sequential combination of open (within capillary proper) and closed (within postcapillary vasculature) systems. The role of luminal vascular carbonic anhydrase in capillary CO2 reactions is strongly dependent on beta nonHCO3. Perfusate nonbicarbonate buffer capacity must be considered when the results of experimental studies of transcapillary CO2 exchange and/or intravascular pH equilibration are interpreted. PMID- 1757372 TI - Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m. AB - Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757373 TI - Effect of lung volume and positional changes on pulmonary diffusing capacity and its components. AB - Normal subjects have a larger diffusing capacity normalized per liter alveolar volume (DL/VA) in the supine than in the sitting position. Body position changes total lung diffusing capacity (DL), DL/VA, membrane conductance (Dm), and effective pulmonary capillary blood volume (Qc) as a function of alveolar volume (VA). These functions were studied in 37 healthy volunteers. DL/VA vs. VA yields a linear relationship in sitting as well as in supine position. Both have a negative slope but usually do not run parallel. In normal subjects up to 50 yr old DL/VA and DL increased significantly when subjects moved from a sitting to a supine posture at volumes between 50 and 100% of total lung capacity (TLC). In subjects greater than 50 yr old the responses of DL/VA and DL to change in body position were not significant at TLC. Functional residual capacity (FRC) decreases and DL/VA increases in all normal subjects when they change position from sitting to supine. When DL/VA increases more than predicted from the DL/VA vs. VA relationship in a sitting position, we may infer an increase in effective Qc in the supine position. In 56% of the volunteers, supine DL was smaller than sitting DL despite a higher DL/VA at FRC in the supine position because of the relatively larger decrease in FRC. When the positional response at TLC is studied, an estimation obtained accidentally at a volume lower than TLC may influence results. Above 80% of TLC, Dm decreased significantly from sitting to supine. Below this lung volume the decrease was not significant. The relationship between Qc and VA was best described by a second-order polynomial characterized by a maximum Qc at a VA greater than 60% of TLC. Qc was significantly higher in the supine position than in the sitting position, but the difference became smaller with increasing age. In observing the sitting and supine positions, we saw a decrease in maximum Qc normalized per square meter of body surface area with age. PMID- 1757374 TI - Extracellular Ca2+ mobilization in potential-dependent contraction of trachealis of maturing swine. AB - We studied the effect of maturation on potassium-induced parasympathetic activation and Ca2+ entry in tracheal smooth muscle (TSM) from fifteen 2-wk-old (2ws) and sixteen 10-wk-old (10ws) male domestic farm swine. Atropine (10(-7) M) caused inhibition of the maximal contraction elicited by potassium to 50.3 +/- 2.6% maximum of control response (P less than 0.001) in TSM from 2ws but had no significant effect in TSM from 10ws (94.6 +/- 4.2% maximum; P = NS vs. control). Verapamil (10(-7) M) plus 10(-7) M atropine reduced contraction elicited by potassium in both 2ws (23.7 +/- 5.8% maximum; P less than 0.001 vs. control) and 10ws (50.6 +/- 6.3% maximum; P less than 0.001 vs. control, P less than 0.05 vs. 2ws); 10(-6)M verapamil caused greater than 95% blockade of contraction caused by potassium in both 2ws and 10ws. In separate studies, atropine-treated strips were equilibrated with extracellular Ca2+ concentrations ([Ca2+]o) ranging from normal (1X [Ca2+]o) to four times normal (4x [Ca2+]o). Increasing [Ca2+]o increased maximal contractile response in atropine-treated TSM strips from 68.7 +/- 3.8% maximum for 1x [Ca2+]o to 100.8 +/- 4.8% maximum for 4x [Ca2+]o (P less than 0.001) in 2ws. Neither atropine nor [Ca2+]o affected maximal responses of TSM in 10ws (103.5 +/- 3.0% maximum for 1x [Ca2+]o; P = NS vs. control). However, in the presence of atropine and verapamil, 4x [Ca2+]o augmented KCl-elicited contraction of TSM from both 2ws (46.9 +/- 6.3% maximum; P less than 0.01 vs. control) and 10ws (78.6 +/- 2.3% maximum; P less than 0.005 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757375 TI - Does the pressor response to ischemic exercise improve blood flow to contracting muscles in humans? AB - The purpose of this study was to determine in humans 1) the gain for the reflex pressor response that occurs when perfusion pressure to rhythmically contracting muscles is reduced and 2) whether the pressor response improves blood flow to the contracting muscles. Six normal subjects performed light, moderate, and heavy rhythmic forearm contractions (30/min) with the forearm enclosed in a Plexiglas box. Pressure in the box was increased 10 mmHg each minute up to 50 mmHg to reduce transmural pressure in the arterial system of the forearm. Mean arterial pressure (MAP) was measured continuously. During light exercise no reflex increase in MAP occurred until box pressure was 50 mmHg. During moderate and heavy exercise MAP began to increase with only 10- to 20-mmHg increases in box pressure. The slope of this increase was 3.5-3.9 mmHg per 10 mmHg of box pressure (approximately 60% of that in dogs). In a further study on six subjects a deep vein draining the active forearm muscles was cannulated and deep venous O2 saturation measured to assess how a 50-mmHg increase in box pressure and subsequent reflex increase in MAP altered blood flow to the contracting muscles during heavy rhythmic exercise. The increase in box pressure reduced blood flow to contracting forearm muscles by 20-25% and was followed by a 19-mmHg increase in MAP that did not appear to improve perfusion of the active muscles. This finding was unexpected, because studies in dogs suggest that the pressor response to rhythmic exercise with restricted muscle blood flow can improve perfusion of the active muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757376 TI - Interfacial transfer kinetics of NO2 into pulmonary epithelial lining fluid. AB - Previous studies, both in intact lungs and epithelial lining fluid (ELF) (J. Appl. Physiol. 68: 594-603, 1990 and J. Appl: Physiol. 69: 523-531, 1990), have suggested that the steady-state absorption of inhaled NO2 is mediated by chemical reaction(s) between NO2 and ELF solute reactants. To characterize the kinetics of NO2 absorption into aqueous biological substrates across a gas-liquid interface, we utilized a closed system of known geometry and initial gas phase [NO2] [([NO2]g)0] to expose ELF (as bronchoalveolar lavage; BAL) and a biochemical model system (glutathione, GSH). Assessments of NO2 reactive uptake, into both GSH and ELF, indicated first-order NO2 kinetics [([NO2]g)0 less than or equal to 10.5 ppm] with effective rate constants of (kNO2)GSH = 4.8 and (kNO2)BAL = 2.9 ml.min-1.cm-2 (stirred). Above 10.5 ppm (1 mM GSH), zero-order kinetics were observed. Both (kNO2)GSH and (kNO2)BAL showed aqueous reactant dependence. The reaction order with respect to GSH and BAL was 0.47 and 0.64, respectively. We found no effect of interfacial surface area or bulk phase volume on kNO2. In unstirred systems, significant interfacial resistance was observed and was related to reactant concentration. These results indicate that NO2 reactive uptake follows first-order kinetics with respect to NO2 ([NO2]g less than or equal to 10.5 ppm) and displays aqueous substrate dependence. Furthermore the site of reactive absorption appears to be limited to near the aqueous surface interface. Unstirred conditions confine interfacial mass transfer kinetics in a dose-dependent manner. These phenomenological coefficients may provide the basis for direct extrapolation to environmentally relevant exposure concentrations. PMID- 1757377 TI - Ventilatory afterdischarge in the awake goat. AB - Ventilatory afterdischarge (VAD) has been defined as a persistent gradually diminishing elevation of ventilatory activity that occurs after withdrawal of a variety of respiratory stimuli. The phenomenon has been well documented in the anesthetized cat, piglet, and lamb in response to electrical stimulation of the carotid sinus nerve. We sought to determine whether VAD could be demonstrated in the standing awake goat (n = 7) by use of an extracorporeal circuit to provide square-wave physiological stimulation of the carotid chemoreceptor (carotid body PO2 40 Torr). After 5 min of isolated carotid body stimulation, the mean time constants for diminishing inspired minute ventilation, tidal volume, and respiratory frequency were 27.7, 34.5, and 25.5 s, respectively. These results indicate that VAD does exist in the awake goat model. A critical factor for the demonstration of VAD is the maintenance of systemic arterial PCO2 (isocapnia) during the period of increased ventilatory activity. If arterial PCO2 is allowed to decrease even slightly during the hyperventilation, the magnitude and duration of VAD are greatly attenuated. PMID- 1757378 TI - Protection of the reperfused heart by L-propionylcarnitine. AB - The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury. PMID- 1757379 TI - Design and implementation of a new computerized system for intraoperative cardiac mapping. AB - A rapid, portable, yet inexpensive and expandable computer-based system utilizing current technology has been developed from experience in the operating room. An efficient operating system well suited for surgery is defined. New technology recording arrays fabricated from multielectrode flexible Kapton strips were developed and found to be easy to use and highly reliable. Novel arrays are created easily for research or special clinical applications. The system displays all incoming data in real time and transfers 16-s epochs to disk on command. After the user defines a beat for analysis, the computer determines the activation time for each channel, rejects unsatisfactory channels, and displays the results for review and modification before plotting the isochronal map on the monitor. The average time to recall data and produce a map is 16 s; if manual review of 120 channels is included, mapping time is less than 4 min. Clinical data recorded during surgery are discussed. The speed and operational ease demonstrated in the operating room make this computer/electrode system valuable both for surgery and for elucidating basic mechanisms of arrhythmias. PMID- 1757380 TI - Contributions of diffusion jet flow and cardiac activity to regional ventilation in CFV. AB - The magnitude and regional distribution of local gas transport during constant flow ventilation (CFV) were quantified by imaging the washout of nitrogen 13 (13NN) from anesthetized and paralyzed mongrel dogs with positron emission tomography. Equal jet flows, through two 2-mm-ID bronchial catheters 1 cm distal to the carina, were adjusted to provide eucapnic CFV (total flow = 57.6 ml.s-1.kg 1). Basal, midheart, and apical transverse sections were studied in supine and prone anesthetized dogs. The ventilation per unit volume (sV) of selected areas was computed from local 13NN concentration vs. time curves during washout. To separate the regional contributions of CFV and cardiogenic oscillation to enhanced molecular diffusion, additional supine dogs were also studied during unilateral CFV. In this protocol the CFV jet flow was delivered to a single lung while the contralateral lung was left apneic. For each lung, washout data were obtained under CFV and apnea both living and postmortem animals. The local contributions of diffusion, CFV jet effects, and cardiac activity to gas transport were evaluated and tested for additive and multiplicative synergistic interactions. The regional distribution of gas transport during CFV was found to be highly nonuniform and characterized by higher ventilation to regions located close to the main bronchi and those located in the direction in which the CFV jet pointed. No major differences were observed between supine and prone positions. This regional pattern of ventilation distribution was found to be the result of complementary and nearly multiplicative interaction between the regional effects of the CFV jet, concentrated in the central airways, and the preferential cardiogenic gas transport enhancement in ventral regions close to the heart. The data were also analyzed with a model that divides the regional diffusive gas transport resistance into a central component, affected by the CFV jet, and a peripheral component, affected only by cardiac activity. This analysis showed substantial regional heterogeneities in the effects of the different gas transport mechanisms, which are consistent with the geometry of the bronchial tree and the location of the heart in the dog. The results indicate that regional nonuniformities must be considered when modeling gas transport in CFV. PMID- 1757381 TI - Lung ischemia-reperfusion injury in awake sheep: protection with verapamil. AB - We caused unilateral lung ischemia-reperfusion injury in awake sheep by simultaneously occluding the left pulmonary artery and left main stem bronchus for 12 h. The occluded left lung was inflated with nitrogen. Reperfusion resulted in an elevation of lung lymph flow from 1.3 to 5.0 ml/15 min and an increase in lymph-to-plsma protein concentration ratios. Reperfusion, but not ischemia alone, caused an increase in wet-to-dry weight ratios in both the reperfused left lung and the contralateral right lung. Granulocytes increased in both lungs during the ischemic period and after reperfusion, and hypoxemia developed after reperfusion. The calcium channel antagonist, verapamil, given just before reperfusion, caused a marked attenuation in the reperfusion-induced changes in the lung lymph variables and wet-to-dry weight ratio. However, verapamil did not affect the hypoxemia or granulocyte sequestration seen after reperfusion. We conclude that reperfusion of ischemic sheep lung results in increased microvascular permeability that can be partially prevented by verapamil. PMID- 1757382 TI - Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure. AB - The arterial blood pressure (BP) components of the Valsalva maneuver (VM) were analyzed to ascertain whether they could be used as an index of adrenergic regulation of the circulation. We studied a control and three age- and sex matched patient groups. Sympathetic adrenergic failure was graded on the basis of the degree of systolic BP (SBP) reduction during tilt: orthostatic hypotension (OH; SBP greater than 30 mmHg), borderline OH (BOH; 30 less than SBP greater than 10 mmHg), and sympathetic sudomotor failure (SSF). Controls exhibited a biphasic phase II, consisting of a modest decrement (early phase II) followed by a rise in BP (late phase II; II1) above resting values. All the patient groups including SSF exhibited a significant reduction in II1. An excessive BP fall in phase II and an absent phase IV overshoot were observed in the OH group. BOH and, to a lesser extent, SSF groups showed a significant reduction in phase IV overshoot. We conclude that BP changes during VM will detect adrenergic vasoconstrictor failure with greater sensitivity than orthostatic BP recordings. PMID- 1757383 TI - Leg exercise conditioning increases peak forearm blood flow. AB - To examine whether forearm vascular adaptations could occur after upright-leg exercise training, the reactive hyperemic blood flow after 10 min of forearm circulatory arrest (RHBF10) was studied. RHBF10 was examined in seven subjects before, at 2 wk, and after the completion of 4 wk of bicycle ergometer training. Maximal O2 consumption (VO2max) for leg ergometer work increased 13% (P less than 0.05) over 4 wk. Over that period of time RHBF10 in the forearm increased 50% (P less than 0.05), with a reciprocal drop in minimum vascular resistance. Resting heart rate decreased 15% (P less than 0.05) during the same period. Changes in RHBF10 and VO2max were noted after 2 wk of training. Mean arterial pressure did not change. We conclude that vascular adaptations can occur in the forearm muscle beds, even though the training regimen is designed to condition the lower extremities. PMID- 1757384 TI - Initiation of oral breathing in lambs in response to airway obstruction: mechanisms. AB - Our aim was to assess the mechanisms determining the reflex formation of an oral airway in response to nasal obstruction (NO) and tracheal obstruction (TO). In nine conscious lambs (14-37 days old) NO was effected by blockade of nasal tubes; TO was later effected by blockade of an endotracheal tube. We measured arterial O2 saturation, PO2, PCO2, and pH and the depth and duration of inspiratory efforts when mouth opening (MO) occurred. Responses were compared when NO and TO followed breathing of room air, rebreathed air, and 100% O2. After both NO and TO, MO was initiated most rapidly after lambs rebreathed air and least rapidly after they breathed 100% O2. Similar changes in blood gases and pH were measured when MO occurred after air breathing and rebreathing; however, the extent of these changes was greater during TO than during NO. After 100% O2 was breathed, MO occurred when lambs were still hyperoxic, but they were more hypercapnic and acidemic than after breathing air or rebreathed air. There were no differences, related to prebreathed gases or site of airway occlusion, in the depth of inspiratory efforts at the time of MO. We conclude that the formation of an oral airway requires a critical level of inspiratory drive in the presence of airway obstruction. After the prebreathing of different gases, differences in response latency and blood gases at the time of MO can be attributed to the attainment of this threshold level of inspiratory drive. The formation of an oral airway is facilitated by, but not dependent on, receptors in the upper airway. PMID- 1757385 TI - Regional deformation of the canine diaphragm. AB - To follow regional deformation of the diaphragm in dogs, radiopaque markers were implanted under surgical anesthesia into different anatomic regions of the muscle in triangular arrays (approximately 1 cm to a side). After recovery from surgery, changes in area and shape of the triangles were followed with biplane cinefluorography during quiet breathing and during inspiratory efforts against an occluded airway (Mueller maneuvers). From changes in shape of the triangles during contraction, area changes were decomposed into a major direction and magnitude of shortening (Eg1) and a minor length change (Eg2) perpendicular to Eg1, both expressed as a fraction of initial length at end expiration. With the use of these techniques, systematic differences in regional area change were observed in different parts of the diaphragm during inspiratory efforts at different lung volumes. Regional area always decreased during contraction in the crural and midcostal zones of apposition to the rib cage. Area decreased less and often increased during inspiratory efforts in the costal dome near the central tendon and in the costal region near its rib cage insertion. Differences in regional area change were not due to differences in the Eg1 in different parts of the diaphragm but were a consequence of differences in widening of the muscle along Eg2 perpendicular to the direction of Eg1. As lung volume was passively increased above functional residual capacity, regional area decreased in all parts of the diaphragm except in the costal regions near rib cage insertion, where area increased. PMID- 1757386 TI - Motoneuron and muscle fiber succinate dehydrogenase activity in control and overloaded plantaris. AB - To determine the level of coordination in succinate dehydrogenase (SDH) activity between plantaris motoneurons and muscle fibers, the soleus and gastrocnemius muscles were bilaterally excised in four cats to subject the plantaris to functional overload (FO). Five normal cats served as controls. Twelve weeks after surgery the right plantaris in each cat was injected with horseradish peroxidase to identify plantaris motoneurons. SDH activity then was measured in a population of plantaris motoneurons and muscle fibers in each cat. Control motoneurons and muscle fibers had similar mean SDH activities and a similar relationship between cell size and SDH activity. After FO, muscle fiber size doubled and mean muscle fiber SDH activity halved. Motoneuron mean SDH activity and size were unaffected by FO. Total SDH activity was unchanged in both the motoneurons and muscle fibers after FO. These changes suggest a selective increase in contractile proteins with little or no modulation of mitochondrial proteins in the muscle fibers, because total SDH activity was unchanged in muscle fibers after FO. These data demonstrate that although mean SDH activities were similar in control motoneurons and muscle fibers, mean SDH activities in these two cell types can change independently. PMID- 1757387 TI - Intracranial self-stimulation motivates treadmill running in rats. AB - Most animal running models have traditionally used aversive motivators to induce exercise tasks. This study demonstrates treadmill running motivated by reinforcement of intracranial self-stimulation (ICSS), providing an alternative model with which to study physiological responses to exercise. Twenty-nine male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the ventral tegmental area of the brain. After 7 days of operant lever-press training for ICSS, rats that pressed at least 50 presses/min were randomly divided into three conditions: exercise-reinforcing brain stimulation (Ex-St), exercise-aversive shock (Ex-Sh), and sedentary controls (C). Ex-St and Ex-Sh ran for 30 min at 25 m/min at 5% grade for 2 wk with ICSS and electric shock as the motivator, respectively, while C did not run. At the end of 2 wk, Ex-St and Ex-Sh performed an endurance run. Results show that Ex-St ran longer than Ex-Sh [63 +/- 10 vs. 42 +/- 10 (SD) min; P less than 0.05]. HR was higher in Ex-St than in C (P less than 0.05). Rectal temperature increased similarly in both exercise groups. This model provides a highly effective method to motivate treadmill running in rats and as such can be used to characterize physiological responses to exercise without the potentially confounding influence of stress associated with an aversive shock motivator. PMID- 1757388 TI - Circadian rhythm in airway responsiveness and airway tone in patients with mild asthma. AB - To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17-65) and their mean daytime FEV1 was 99 +/- 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV1) and the provocative concentrations of histamine and methacholine necessary to decrease FEV1 by 20% (PC20FEV1) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC20FEV1 to histamine and methacholine showed significant and reproducible circadian variations in all cases (P less than 0.01 each) with a mean amplitude of 1.00 +/- 0.17 (SD) doubling concentrations for histamine and 1.35 +/- 0.29 doubling concentrations for methacholine. The amplitude of PC20FEV1 was significantly larger (P less than 0.05) and the time of maximum responsiveness was significantly earlier (P less than 0.05) with methacholine compared with histamine. FEV1 showed significant (P less than 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV1 and PC20FEV1 was significant (P less than 0.05) in 5 of 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757389 TI - Extra-alveolar veins are contiguous with, and leak fluid into, periarterial cuffs in rabbit lungs. AB - We previously observed physiological evidence that arterial and venous extra alveolar vessels shared a common interstitial space. The purpose of the present investigation was to determine the site of this continuity to improve our understanding of interstitial fluid movement in the lung. Orange G and Evans blue dyes were added to the arterial and venous reservoirs, respectively, of excised rabbit lungs as they were placed 20 cmH2O into zone 1 (pulmonary arterial and venous pressures = 5 cmH2O, alveolar pressure = 25 cmH2O). After 10 s or 4 h the lungs were fixed by immersion in liquid N2, freeze-dried, cut into 5-mm serial slices, and examined by light macroscopy. Serial sections of 0.25-0.5 mm were subsequently examined by scanning electron microscopy. In the animals subjected to the zone 1 stress for 4 h, arterial and venous extra-alveolar vessels were surrounded by cuffs of edema. The edema ratio (cuff area divided by vessel lumen area) was greater around arteries than veins and decreased with increasing vessel size. Periarterial cuffs usually contained orange dye and frequently contained both orange and blue dye. Lymphatics containing orange or blue dye were frequently seen in periarterial cuffs. Scanning electron microscopy demonstrated that extra-alveolar veins of approximately 100 microns diameter were anatomically contiguous with arterial extra-alveolar vessel cuffs. In rabbit lungs, both arterial and venous extra-alveolar vessels (and/or alveolar corner vessels) leak fluid into perivascular cuffs surrounding arterial extra-alveolar vessels, and lymphatics located in the periarterial cuff contain fluid that originates from both the arterial and venous extra-alveolar vessels. PMID- 1757390 TI - Effect of work load on cutaneous vascular response to exercise. AB - The purpose of the present study was to examine whether intensity of exercise affects skin blood flow response to exercise. For this purpose, six healthy men cycled, in a random order on different days, for 15 min at 50, 60, 70, 80, and 90% of their maximum oxygen consumption (VO2max) at a room temperature of 25 degrees C. At the end of exercise, esophageal temperature (Tes) averaged 37.4 +/- 0.2, 37.7 +/- 0.2, 37.9 +/- 0.2, 38.6 +/- 0.3, and 38.9 +/- 0.4 degrees C (SE) at the 50, 60, 70, 80, and 90% work loads, respectively. At the two highest work loads, no steady state was observed in Tes. Skin blood flow was estimated by measuring forearm blood flow (FBF) with strain-gauge plethysmography and by laser Doppler flowmetry on the upper back. Both techniques showed that skin blood flow response to rising Tes was markedly reduced at the 90% work load compared with other work loads. At the end of exercise, FBF averaged 7.5 +/- 1.7, 10.7 +/- 3.1, 9.6 +/- 2.1, 11.3 +/- 2.6, and 5.4 +/- 1.3 (SE) ml.min-1.100 ml-1 (P less than 0.01) at the 50, 60, 70, 80, and 90% VO2max work loads, respectively. The corresponding values for Tes threshold for cutaneous vasodilation (FBF) were 37.42 +/- 0.16, 37.48 +/- 0.13, 37.59 +/- 0.13, 37.79 +/- 0.19, and 38.20 +/- 0.22 degrees C (P less than 0.05) at 50, 60, 70, 80, and 90% VO2max, respectively. In two subjects, no cutaneous vasodilation was observed at the 90% work load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757391 TI - Time domain analysis of oxygen uptake during pseudorandom binary sequence exercise tests. AB - Pseudorandom binary sequence (PRBS) exercise tests involve repeated switching between two work rates (WR) according to a computer-generated pattern. This paper presents an approach to analysis of O2 uptake (VO2) in the time domain. First, the autocorrelation function (ACF) of the input WR was recognized to be a triangular-shaped pulse that can be taken to be equivalent to a ramp increase followed by a ramp decrease in WR. Then the cross-correlation function of the input (WR) and the output (VO2) was treated as if it were the response to a triangular-shaped pulse. The cross-correlation function was analyzed by fitting a linear summation of the ramp form of a two-component exponential function to this triangular pulse. VO2 responses of eight subjects were obtained from two different PRBS tests, as well as step changes in WR. The first PRBS test consisted of 15 units, each 30 s in duration. Its ACF had a base width of 60 s. The ramp increase-ramp decrease model fit the data throughout the range of response. The second PRBS test had 63 units, each 5 s in duration; thus its ACF base width was 10 s. Again, the ramp model fit adequately. The data from the second PRBS test could be fit by the impulse form of the two-component exponential equation, although the fit in the first 30 s tended to be poorer. The time constants of VO2 dynamics estimated from step and PRBS tests were not significantly different. PRBS tests can be analyzed in the time domain, and the indicators of system dynamics reflect physiological properties similar to those investigated during step changes in WR. PMID- 1757392 TI - Intracranial self-stimulation motivates weight-lifting exercise in rats. AB - The purpose of this study was to determine the feasibility of using a positive reinforcement protocol to motivate weight-lifting exercise in rats. Intracranial self-stimulation was used to induce weight-lifting exercise. Bipolar electrodes were implanted in the ventral tegmental area of rats, and the animals were trained to bar press on a continuous reinforcement schedule for electrical brain stimulation. Animals with response rates of 1,200-1,500 presses/h were then trained with a discriminative light stimulus to alternate between a normally positioned bar and an elevated bar that could be reached only by standing on the hindlimbs. The animals were fitted with a weighted jacket at a starting resistance of 5-10% of their body weight. Weight-training sessions were conducted 5 days/wk for 10 wk. Training consisted of 600 presses/session, alternating every 15 presses between the low and high bars. At the beginning of each subsequent week, the resistance was progressively increased, with some animals eventually training at resistances greater than 50% of their body weight. At the end of the training period, the rats were lifting over 550% of the starting weight. Gastrocnemius size and mean fiber diameter were increased in the weight-lifting animals. This model combines exercise with positive incentive and has the advantages of being relatively easy to implement and not producing any apparent physical or mental trauma in the animal. PMID- 1757393 TI - In vivo growth patterns of human lung tumors in three-dimensional histoculture. PMID- 1757394 TI - Heterogeneity in antigenic expression and radiosensitivity in human colon carcinoma cell lines. AB - A panel of human colon carcinoma cell lines were characterized regarding both antigenic heterogeneity and variations in radiosensitivity. Monoclonal antibodies were used to study the expression of carcinoembryonic antigen (CEA), gastrointestinal cancer antigen (GICA or CA 19-9) and carcinoma-associated antigen (CA-50). Radiosensitivity was studied with the clonogenic survival technique. Three cell lines, LS 174T, HCTC, and SW 1116 stained positive for all three antigens. HT-29 was positive for CA 19-9 and CA-50 whereas Caco-2 was positive for CEA and CA 19-9. The cell lines SW 620 and LIM 1215 only stained positive for one of the antigens, CA-50 and CEA, respectively. In nearly all positive cases the stainings were very heterogeneous with mixtures of positive and negative cells. One exception was the HCTC cells which stained homogeneously for the CA 19-9 and CA-50 antigens. The neuroendocrinelike COLO 320 cells were negative in all cases. The radiosensitivity varied strongly between the cell lines with Dq-values between 0.8 and 1.9, extrapolation numbers between 2.0 and 4.7, Do-values between 1.1 and 2.8. The surviving fraction at 2 Gy varied between 0.3 and 0.7 with HCTC as the most radiosensitive and HT-29 as the most radioresistant cell line. Thus, there were differences in antigenic expression and intrinsic radiosensitivity between the cell-lines and antigenic heterogeneities within each cell line. The analyzed panel of cell lines will be valuable in studies of dose-effect relations for monoclonal antibodies labeled with toxic radionuclides simulating both antigenic heterogeneity and variations in radiosensitivity. PMID- 1757395 TI - Proliferation and differentiation of mouse uterine epithelial cells in primary serum-free culture: estradiol-17 beta suppresses uterine epithelial proliferation cultured on a basement membrane-like substratum. AB - The effects of different substrata and estradiol-17 beta (E2) on proliferation and differentiation of mouse uterine epithelial cells was examined in a serum free primary culture system. When cultured on rat-tail collagen gels, the epithelial cells rapidly increased in number to form a simple squamous cell layer that exhibited a relatively undifferentiated state (a few short microvilli, no secretory granules, and poorly developed endoplasmic reticulum). Addition of E2 into the culture medium did not affect the proliferation of epithelial cells on collagen gel. Uterine epithelial cells grown on a reconstituted basement membrane like substratum (Matrigel) formed a simple columnar/cuboidal cell layer exhibiting fully developed characteristics (many long microvilli, many secretory granules, and fully developed endoplasmic reticulum). Examination of epithelial proliferation by counting substratum-attached cell number revealed only a slow increase in cell growth on Matrigel, and E2 did not significantly affect it. However, measurement of proliferating cells by labeling cells with 5-bromo-2' deoxyuridine revealed that cells on Matrigel were replicating and that E2 (10(-7) to 10(-11) M) actually significantly suppressed epithelial proliferation. However, there was not an effect of E2 on total cell number, indicating that the cells in control medium replicate faster and detach more readily from the substratum than those in E2-supplemented medium on Matrigel. Thus, it is probable that E2 significantly reduces the rate of cell detachment from the substratum, which may mimic the in vivo condition where significant decrease in apoptosis or cell death is induced by E2. PMID- 1757396 TI - A method for the harvest, culture, and characterization of human adult atrial myocardial cells: correlation with age of donor. AB - Myocardial cell culture methods are now well established for animal and fetal human tissue. We present here a method for harvesting and culturing adult human atrial myocardiocytes. Cells are obtained from fresh atrial tissue normally discarded after being removed to cannulate the right atrium during open heart surgery. The atrial tissue is minced and then digested using collagenase. The single cell suspension is initially cultured in serum-containing growth medium, then transferred to defined medium, selective for myocardial cell growth. The cells are characterized by immunoperoxidase stains and transmission electron microscopy. The cultured cells stain positive for myoglobin, whereas control cultured fibroblasts and endothelial cells do not. Electron microscopy shows the presence of numerous myofibrils, Z-bodies, pleomorphic mitochondria, and secretory granules. The chronological age of the donor was an important factor in culturing the adult tissue, the younger tissue correlated with a higher success rate. This method provides a means for in vitro study of human adult myocardial cells and provides guidelines for appropriate atrial tissue to use. PMID- 1757397 TI - A primary culture system of adult rat heart cells for the study of toxicologic agents. AB - Tricyclic antidepressants (TCAs) are currently used in the treatment of mental depression and nocturnal enuresis. Clinically, these drugs are useful; however, cardiotoxicity can occur even with therapeutic dosages. For example, TCAs are known to alter myocardial function, induce arrhythmias, and produce heart block in individuals with a normal cardiovascular history. The present study was undertaken to establish a culture system of spontaneously contracting adult primary myocardial cells for toxicologic testing and to examine their contractility, morphology, and lactate dehydrogenase release (LDH) after treatment with one of the most cardiotoxic TCAs, amitriptyline. Primary myocardial cell cultures were obtained from approximately 60- to 90-day-old Sprague-Dawley rats. After the cells had been grown in culture for 11 days, they were treated with amitriptyline (1 x 10(-3), 1 x 10(-4), and 1 x 10(-5) M) for 2 to 24 h. The highest concentration of amitriptyline (1 x 10(-3) M) completely destroyed the cardiac muscle cells. In addition to moderate and severe vacuole, granule, and pseudopodia formation, all contractile activity was inhibited as early as 2 h after exposure to the intermediate concentration of 1 x 10(-4) M amitriptyline. Significant LDH release did not occur until 8 h after treatment with this intermediate concentration. Even though there was no significant LDH release at all 3 time points tested, there was a 50% decrease in beating activity (154 +/- 9 to 77 +/- 5 beats/min) and initiation of vacuole formation by 2 h with the lowest concentration of amitriptyline (1 x 10(-5) M). This study presents a new apparatus for the isolation of adult cardiac myocytes for the establishment of primary cell cultures for toxicologic testing. Furthermore, these data demonstrate that amitriptyline induces a concentration- and time-dependent cardiotoxic profile in a model of spontaneously contracting adult cardiac muscle cells in culture. PMID- 1757398 TI - Epithelial differentiation in the absence of extracellular matrix. AB - To investigate the regulation of epithelial differentiation, normal human epidermal keratinocytes were cultured floating on the surface of culture medium without attachment to a solid substrate. Keratinocytes spread out on the surface of the medium, proliferated and differentiated either into several flat lacy sheets 1 to 3 cells thick (on medium containing 0.15 mM calcium) or formed one single aggregate of cells from 5 to 15 cells in thickness on medium containing 1.15 mM calcium. The cell aggregates demonstrated a pattern of ordered epithelial differentiation. Levels of progressive differentiation resembling the structure of normal human epidermis were identified by light microscopy, immunohistochemistry, and electron microscopy. Differentiation proceeded from cells at the air side toward cells at the medium side with basal appearing cells on the air side and keratinocytes expressing filaggrin and involucrin on the side toward the medium. These results demonstrate that organized epithelial differentiation can occur in the absence of extracellular matrix. In contrast with other air-liquid interface cultures, epithelial differentiation in the absence of extracellular matrix progresses from air towards medium. PMID- 1757399 TI - Reduction of proliferative heterogeneity of CHEF18 Chinese hamster cell line during the progression toward tumorigenicity. AB - Doubling time and generation time represent two parameters by which the proliferation of cultured mammalian cells can be monitored. In this study we report the characterization of CHEF18 Chinese hamster cell line during the progression toward tumorigenicity by analysis of doubling time and generation time. The two parameters reveal that the proliferation was initially different, indicating the presence of a proliferative heterogeneity among the cycling cells. The progressive reduction up to the disappearance of this discrepancy suggests that a modification of the length of some phases of the cell cycle may have occurred during the progression toward tumorigenicity. However, the hypothesis that the shortening of doubling time might be due to a continuous coming out of cells from the cell cycle rather than to a shortening of the cell cycle is presented. PMID- 1757400 TI - Sulfation and glucuronidation of acetaminophen by cultured hepatocytes reproducing in vivo sex-differences in conjugation on Matrigel and type 1 collagen. AB - The sulfate and glucuronide conjugation of acetaminophen (APAP) by hepatocytes cultured on Matrigel or type 1 collagen was compared to APAP metabolism in vivo. The metabolic fate of low (15 mg/kg), medium (125 mg/kg), and high (300 mg/kg) doses of APAP injected intraperitoneally were determined in male and female rats. Males excreted more APAP as the sulfate conjugate than females, which correlated with the twofold greater APAP sulfotransferase activity in the male vs. females (301 +/- 24 vs. 156 +/- 18 pmol.mg-1 protein.min-1). Also, as sulfate conjugation became saturated, there was a dose-related shift in APAP metabolism from sulfate to glucuronide conjugation in both sexes. After death, the livers of the same animals were perfused with collagenase and the hepatocytes cultured in modified Waymouth's medium on either Matrigel or rat-tail collagen, with various doses of APAP (0, 0.125, 0.25, 0.5, and 1.0 mM). Sex differences in APAP sulfation and glucuronidation persisted in culture for up to 4 days, with sulfation predominating in the male similar to in vivo. With increasing APAP concentration (dose), there was a saturation of sulfate conjugation and a shift to glucuronidation as observed in vivo. Sex differences in APAP sulfation and glucuronidation were no longer significant by Day 4 in culture. Sulfation, and to a lesser extent, glucuronidation, were more stable on Matrigel than collagen. We concluded that APAP metabolism of freshly isolated hepatocytes could replicate in vivo sex differences in conjugation, and that Matrigel was superior to collagen as substrate. PMID- 1757401 TI - The social dimension of health status measures in rheumatoid arthritis. AB - Fifty-six patients with rheumatoid arthritis (RA) were assessed on two occasions three months apart. They completed two health status instruments--the Arthritis Impact Measurement Scales (AIMS) and the Nottingham Health Profile (NHP)--and the Beck Depression Inventory. In addition, clinical and serological data were gathered in order to calculate severity of disease according to the Mallya and Mace index. Health status instruments and the severity of disease index showed agreement in the assessment of mobility; similar agreement was found for different assessments of emotions. However, the two instruments provided social interaction scores with little agreement either cross-sectionally or in terms of change over time. It is argued that the generic NHP may be a valid instrument as an outcome measure in RA but the NHP and AIMS assess different aspects of social interaction. Care is needed in the selection of outcome measures to evaluate interventions. PMID- 1757402 TI - Provision of physiotherapy and occupational therapy in outpatient departments and day hospitals for stroke patients in Nottingham. AB - The provision of rehabilitation for stroke patients discharged from hospital in Nottingham was determined in three ways: a longitudinal study of consecutive stroke patients discharged from hospital, a cross-sectional survey of stroke patients attending physiotherapy (PT) and occupational therapy (OT) outpatient departments (OPDs), and an observational study of patients attending for rehabilitation at day hospitals (DHs) and PT and OT OPDs. In the longitudinal study 17% of patients went to DHs and 20% to OPDs. During the cross-sectional study patients most commonly attended twice weekly. Twenty-four per cent of DH attenders were 18 months post-stroke. In the observational study, the proportion of time spent in therapy was 22% in DHs, 38% in PT OPDs, 48% in OPD OT, and 51% in those attending both PT and OT OPDs. Day hospitals are now a major facility for the rehabilitation of stroke outpatients. OPDs may deliver rehabilitation more efficiently than DHs, and both OPDs and DHs compare favourably when compared to inpatient rehabilitation in this respect. PMID- 1757403 TI - Posturographic evaluation of the proprioceptive effect of ankle orthoses in healthy volunteers. AB - This study analyses the proprioceptive effect of wearing a unilateral and then bilateral ankle orthosis on 34 healthy volunteer subjects by posturography. An elastic orthosis with a ligamentous support band was used, and evaluation was performed by a posturographic statokinesimetric platform. Three tests, one without an orthosis, one with one orthosis, and one with two orthoses, were recorded for each volunteer. The results and statistical analyses demonstrated a significant difference in the antero-posterior measurement between the test without ankle orthosis and the tests with one and with two orthoses. This study provides information about the prophylactic effect of wearing a flexible support; it appears that there are important inter-individual variations in postural equilibrium, and the wearing of prophylactic ankle orthoses should be reserved for subjects after a posturographic examination. PMID- 1757404 TI - Electromyographic study of sternocleidomastoid and scalene muscles in tetraplegic subjects during respiration. AB - An electromyographic investigation of inspiratory respiratory muscles was carried out in six tetraplegic and two normal subjects using needle electrodes. When the normal subjects were using tidal breathing there was no activity present. In the majority of tetraplegic subjects, activity was present in the scalene muscle during tidal breathing. This activity became more marked during deep inspiration. The muscles were hypertrophied and these muscles filled an important respiratory role. PMID- 1757405 TI - Trend line influence on visual analysis of single-subject data in rehabilitation research. AB - Single-subject design and n of 1 randomized clinical trials are being advocated as methods of conducting clinical research in rehabilitation environments. The traditional procedure for interpreting data from such designs is visual analysis. This study examined the effect of including trend lines on the visual judgements made from single-subject data. Twenty-four hypothetical single-subject A-B designs were presented to 20 rehabilitation therapists for visual interpretation. The graphs represented traditional single-subject designs, including a baseline and treatment phase. Trend lines were computed and included in both phases of the design as an adjunct to visual analysis. The interrater reliability of the visual judgements was calculated using the intraclass correlation coefficient and ranged from 0.54 to 0.90. The results suggest that adding trend lines to graphed data presented in single-subject designs can improve the consistency of visual judgements. Implications for using adjuncts to graphing data points in single subject rehabilitation research are discussed. PMID- 1757406 TI - Experience of a self-care unit as part of a hospital-based rehabilitation service. AB - The nature, advantages and disadvantages, and cost of a hospital-based self-care unit as part of a rehabilitation service are described. The unit's operational policy is critically examined after analysing the records of 40 patients admitted consecutively over a 2-year period and conducting interviews with 27 patients between 4 and 48 weeks after discharge. It is concluded that, compared with a hospital ward, a self-care unit is inexpensive to run and helps to prevent patients from giving up their homes and being admitted to residential homes prematurely. In addition to an assessment and confidence-building role, the unit provides a more appropriate and acceptable environment for patients waiting housing alteration or rehousing than a hospital ward. PMID- 1757407 TI - Liquid chromatographic determination of the processing aid 4-hexylresorcinol in shrimp. AB - A rapid, sensitive, liquid chromatographic (LC) method has been developed for determination of residuals of the processing aid, 4-hexylresorcinol, on shrimp meat. An aqueous homogenate of shrimp meat is extracted with ethyl acetate followed by precolumn preparation on a silica Sep-Pak cartridge. LC determination is preformed with a Nova-Pak C18 column, with UV detection at 214 nm. Sensitivity was 0.006 micrograms, and recovery from shrimp meat samples of known 4 hexylresorcinol addition was 94%. Shrimp treated with 4-hexylresorcinol under the recommended dip protocol had mean residuals of 1.18 ppm, with a standard deviation of 0.13 ppm. PMID- 1757408 TI - Supercritical fluid extraction/enzyme assay: a novel technique to screen for pesticide residues in meat products. AB - The novel combination of supercritical fluid extraction (SFE) with an enzyme assay system has been used to screen meat products to detect the presence of pesticides. Analytes are collected in water by expanding supercritical carbon dioxide to atmospheric pressure through a restrictor and into an aqueous phase. The solution is then tested for the presence of pesticide residues by enzyme assay. Two experimental approaches have been used. Alachlor-fortified lard and bovine liver were monitored by static SFE coupled with an enzyme immunoassay. SFE of carbofuran-fortified frankfurters was coupled with an enzyme assay based on cholinesterase inhibition. A major benefit of the SFE/enzyme assay technique over conventional screening techniques is that the analyst is not exposed to organic solvents. PMID- 1757409 TI - Limited survey of residual tetracyclines in tissues collected from diseased animals in Aichi Prefecture, Japan. AB - Tissues were collected to survey the actual conditions of tetracycline antibiotics (TCs) residues in slaughtered animals that did not pass inspection at slaughterhouses in Aichi Prefecture, Japan, because of the presence of disease symptoms. Tissues were analyzed by liquid chromatography. Among 271 samples, 49 (18.1%) were positive for oxytetracycline (OTC), 5 (1.8%) for chlortetracycline (CTC), and 5 (1.8%) for doxycycline (DC), respectively. One sample (cattle kidney) was positive for both OTC and DC. However, tetracycline was not detected in any samples. Percentage frequencies of TCs residues were 29.1% (37/127) and 15.2% (22/144) for cattle and hogs, respectively. Kidney samples showed higher incidence of TCs residues and 1.5-7 times higher residual concentrations than liver and miscellaneous samples. PMID- 1757410 TI - An analytical survey of aflatoxins in tissues from swine grown in regions reporting 1988 aflatoxin-contaminated corn. AB - A joint project was undertaken by the Food Safety and Inspection Service (FSIS) and the Agriculture Research Service branches of the U.S. Department of Agriculture to determine the presence of aflatoxins in the U.S. meat supply during a drought year. In 1988, high incidences of aflatoxins occurred in corn grown in regions of the Midwest, Southeast, and South. Six states were identified as having serious aflatoxin contamination in their corn crop: Virginia, North and South Carolina, Texas, Iowa, and Illinois. Swine liver and pillars of diaphragm (muscle) tissues were sampled by federal FSIS Inspectors in plants located in these states. A worstcase sampling plan was conducted. Samples were taken in January 1989 from hogs fed corn soon after harvest and in April 1989 from hogs fed corn originally stored and then fed in the spring. A modification of the official AOAC method for the thin-layer chromatography (TLC) determination of aflatoxins in animal tissue was used to permit quantitation by LC with fluorescence detection. The official AOAC TLC confirmation of identity method was used to confirm all positive samples with B1 concentrations greater than 0.04 ppb and M1 concentrations greater than 0.1 ppb. Sixty samples in the January group and 100 samples in the April group were assayed. Concentrations of aflatoxins B1 and M1 in the first group of pig livers ranged from 0.04 to 0.06 ppb. The identity of aflatoxin B1 was confirmed in all positive samples. Aflatoxin M1 could not be confirmed in any of the positive liver samples because the method was insufficiently sensitive for this aflatoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757411 TI - Polyvinyl chloride matrix membrane electrodes for manual and flow injection analysis of chloroquine in pharmaceutical preparations. AB - Two types of polyvinyl chloride (PVC) matrix membrane electrodes responsive to the antimalarial drug chloroquine have been constructed, electrochemically evaluated, compared and used in pharmaceutical analysis. Type 1 is the classic PVC model with chloroquine-tetraphenylborate (TPB) sensor; Type 2 is a coated silver disk without internal filling solution. Both electrode types exhibited rapid linear potentiometric response to the logarithmic concentration of diprotonated chloroquine cation in the 10(-1) - 10(-6)M range with calibration slopes 28-30 mV/concentration decade over the pH range 1.8-6.2. These electrodes were sensitive enough to permit determination of chloroquine phosphate at concentrations as low as 5 microgram/mL with good accuracy and precision. Determination of chloroquine in various pharmaceutical preparations using direct potentiometry and potentiometric titration with NaTPB gave an average recovery of 98.8% of the nominal values (SD 0.5%). The Type 2 electrode was also assessed in a flow-through sandwich cell for flow injection analysis. Results were compared with data obtained by the U.S. Pharmacopeia method. PMID- 1757412 TI - Assay of oxolinic acid residues in salmon muscle by liquid chromatography with fluorescence detection: interlaboratory study. AB - A previously developed method that uses a simplified sample preparation and fluorometric detection of liquid chromatographic eluates for the determination of oxolinic acid in salmon muscle has been collaboratively studied. Five laboratories participated in the study to analyze, in quintuplicate, blank salmon muscle fortified at 10, 20, 50, and 100 micrograms/kg (ppb), and 2 incurred samples from salmon given feed with medicated oxolinic acid. The tissue, 2 g mixed with 2 g Na2SO4, is extracted with ethyl acetate and centrifuged, and the solvent is evaporated. The residue is partitioned in a mixture of hexane and 0.01 M oxalic acid, and the aqueous phase is chromatographed using fluorescence detection at 327 nm excitation and 369 nm emission. Mean recoveries ranged from 77.2 to 84.5% in spiked samples with reproducibility relative standard deviation (RSDR) ranging from 11.5 to 18.3%. Treated salmon were found to contain 8.71 and 53.8 micrograms/kg with RSDR of 18.6 and 16.7%, respectively. The corresponding repeatability relative standard deviations (RSDR) were 5.8-12.2%, and 7.7 and 6.2%. The method is recommended for regulatory purposes in Canada. PMID- 1757413 TI - Bacillus stearothermophilus disk assay for determining ampicillin residues in fish muscle. AB - The Bacillus stearothermophilus disk assay for penicillin in milk (AOAC official method) was adapted for the determination of ampicillin in fish muscle. The method was evaluated in 2 species of cultured fish: channel catfish and striped bass. Recoveries of ampicillin ranged from 99 to 104% when muscle specimens from both species were spiked at concentrations of 0.025-1.00 micrograms/g. The lower limit of determination (LOD) was 0.025 micrograms/g. The assay was applied to monitor the elimination of ampicillin from the muscle of striped bass after intravascular administration (dosage of 10 mg/kg body weight). The mean concentrations in the muscle declined from 1.160 micrograms/g at 2 h to 0.063 micrograms/g at 18 h. The half-life of ampicillin in the muscle was 3.6 h. Ampicillin concentrations were below LOD at 24 h. No inhibitory activity was observed in the muscle of control fish. PMID- 1757414 TI - Comparison of automated liquid chromatographic and bioassay methods for determining spiramycin concentration in bovine plasma. AB - The performance of a liquid chromatographic (LC) method for spiramycin measurement in bovine plasma has been compared with that of a microbiological method. Plasma samples were obtained from cattle administered spiramycin intravenously. Comparison tests used were intraclass correlation (r1), correlation (r), and Student's paired t-test. For concentrations lower than 2.5 IU/mL, microbiological values were higher than LC values. This difference in results modified pharmacokinetic interpretation and might be explained by the presence of microbiologically active metabolites. PMID- 1757415 TI - Sensitive and rapid reversed-phase liquid chromatography-fluorescence method for determining bisphenol A diglycidyl ether in aqueous-based food simulants. AB - A method has been developed for determination of bisphenol A diglycidyl ether (BADGE) in 3 aqueous-based food simulants: water, 15% (v/v) ethanol, and 3% (w/v) acetic acid. BADGE is extracted with C18 cartridges and the extract is concentrated under a stream of nitrogen. BADGE is quantitated by reversed-phase liquid chromatography with fluorescence detection. Relative precision at 200 micrograms/L was 3.4%, the detection limit of the method was 0.1 micrograms/L, and recoveries of spiking concentrations from 1 to 8 micrograms/L were nearly 100%. Relative standard deviations for the method ranged from 3.5 to 5.9%, depending on the identity of the spiked aqueous-based food simulant. PMID- 1757416 TI - Potassium as an index of fruit content in baby food products. Part I. Banana containing and apricot-containing products. AB - Percentage ingredient labeling has been proposed for baby foods. We determined whether or not the potassium content of baby foods could be used to verify the quantity of fruit when the characterizing ingredients were apricots or bananas, fruits rich in potassium. Official values for potassium in fruit (USDA Handbook No. 8-9) did not agree well with actual analyses. The potassium levels of products of known composition were accurately predicted from analyses of the actual ingredients used to make the foods. For banana-containing monofruit products of variable or unknown composition, potassium analysis led to fruit level estimates consistent with either the known composition or the label declaration. For products of unknown composition made with apricot concentrate, however, potassium analysis led to fruit level estimates lower than the probable fruit content. The quantity of fruit in baby foods made with potassium-rich fruits can be estimated from the potassium content if the potassium value for the fruit is representative of the actual ingredients used to make the product. If potassium analysis is to be used to verify compliance with percentage ingredient labeling, there must be statutory specification of the single-strength fruit level for fruit reconstituted from concentrate. PMID- 1757417 TI - A new approach to the study of glucosinolates by isocratic liquid chromatography. Part I. Rapid determination of desulfated derivatives of rapeseed glucosinolates. AB - Liquid chromatographic (LC) analysis of desulfated derivatives of rapeseed glucosinolates has been carried out under isocratic elution conditions with different CN-bonded stationary phases. The effects of the eluant composition (water, acetonitrile, and methanol) with the stationary phase (Zorbax CN, Lichrospher CN, and Ultrasphere CN) and temperature (20 and 50 degrees C) are described. An isocratic LC method performed at room temperature using a Lichrospher CN column and water as mobile phase is proposed. The chromatographic analysis can be done in less than 12 min, and it is easier and less expensive than the traditional gradient mode. Four commercial samples of rapeseed containing various quantities of other cruciferous seeds (wild mustard and stinkweed) as an admixture have been analyzed to determine the total glucosinolate content. Relative standard deviations of repeatability of the isocratic and gradient LC methods ranged from 0.4 to 1.7% and from 2.7 to 4.7%, respectively. Comparison of the results showed good agreement between the 2 methods (beter than 98%). PMID- 1757418 TI - Analysis of trypsin inhibitors and lectins in white kidney beans (Phaseolus vulgaris, var. Processor) in a combined method. AB - Buffered saline extraction, affinity chromatography, and Folin-BSA protein assay were used consecutively to provide a combined method for analysis of trypsin inhibitors and lectins in white kidney beans (Phaseolus vulgaris, var. Processor). The method was tested by following the decrease of both antinutritional factors by germination of the beans for 7 days at 20 degrees C. Repeatability coefficients of variation were 2-7.4% for the trypsin inhibitors and 2.2-10% for the lectins. After 7 days of germination, trypsin inhibitors and lectins were reduced by 72 and 92%, respectively. PMID- 1757419 TI - Identification of whale species by thin-layer isoelectric focusing of sarcoplasmic proteins. AB - Thin-layer isoelectric focusing was applied to the identification of whale (Cetacea) species by using water-soluble sarcoplasmic proteins of skeletal muscles. Twenty-eight samples consisting of 4 species (10 samples) of baleen whales (Mysticeti) and 8 species (18 samples) of toothed whales (Odontoceti) were analyzed. Each sample (approximately 1 g) was electrophoresed with Ampholine PAGplate, pH 3.5-9.5. The electrophoretic profiles were species-specific on the 4 toothed whale species that did not have a marked intra-species difference, and all 4 baleen whale species. However, the profiles were not specific on the 4 other dolphin species, even though they were discriminable from the other 4 toothed whale species. Numerical values of pIs and relative peak heights were obtained by densitometric analysis of the isoelectro-focused protein bands. The bands were also species-specific for the 8 toothed whale species mentioned. The values may be applicable to species identification without the need for a standard sample, which may not be readily obtainable. Experiments on test samples of minke and sel whales showed that bloodletting with ice water made the densities of isoelectro-focused bands thinner, although species identification was still possible by using the inside part of muscles. Heat treatment at below 60 degrees C for 10 min caused little denaturation; at higher temperatures the protein bands were diminished in a temperature-dependent fashion. Therefore, the present isoelectric focusing analysis should be applicable to small samples of whale meat, excluding several species of dolphins. PMID- 1757420 TI - Use of the Mycosep multifunctional cleanup column for liquid chromatographic determination of aflatoxins in agricultural products. AB - A liquid chromatographic (LC) technique has been developed that uses the Mycosep multifunctional cleanup (MFC) column. MFC columns provide a rapid 1-step extract purification. They are designed to retain particular groups of compounds that may create interferences in analytical methods. At the same time, MFC columns allow compounds of interest to pass through. In the method presented, test samples are extracted in a blender with acetonitrile-water (9 + 1). A portion of the extract is forced through an MFC column designed especially for analysis of numerous mycotoxins. Analytical interferences are retained, while aflatoxins pass through the column. Aflatoxins B1 and G1 are converted to their hemiacetals by heating a mixture of purified extract and water-trifluoroacetic acid-acetic acid (7 + 2 + 1) at 65 degrees C for 8.5 min. An aliquot of this mixture is analyzed by isocratic LC with acetonitrile-water mobile phase and fluorescence detection. A detection limit of less than 0.5 ng/g for aflatoxin B1 was obtained. Average recoveries greater than 95% total aflatoxins (B1, B2, G1, and G2) and coefficients of variation of less than 3% were obtained. The method was successfully applied to the following commodities: corn, almonds, pista-chios, walnuts, peanuts, Brazil nuts, milo, rice, cottonseed, corn meal, corn gluten meal, fig paste, and mixed feeds. PMID- 1757421 TI - Monitoring aldehyde production during frying by reversed-phase liquid chromatography. AB - Acrolein (2-propenal) and other low molecular weight aldehydes (LMWAs) formed by degradation of the frying medium (triglycerides) were monitored by liquid chromatography (LC) during preparation of fried items. LMWA contents of coatings from codfish and of doughnuts and their volatiles that codistill with steam are monitored by trapping the vapors and distillate from the food matrix in a 2,4 dinitrophenylhydrazine solution. The resulting hydrazones are partitioned from the aqueous phase, first into isooctane and then into acetonitrile for LC analysis. The hydrazones are separated and quantified on a C18 reversed-phase column with acetonitrile-water as the mobile phase. LMWAs are confirmed by gas chromatography/mass spectrometry. No difference was found in LMWA content in coatings from fish fillets fried at 182 or 204 degrees C. Cake doughnuts were higher in acrolein content than yeast-raised doughnuts prepared under similar conditions. Freshness of the frying medium, frying time, and batch size did not seem to influence LMWA production from doughnuts. Results indicated that most of the LMWAs formed codistilled with steam during frying rather than remaining with the food item. PMID- 1757422 TI - Improved method for determination of polynuclear aromatic hydrocarbons in pharmacopoeial paraffin and mineral oils. AB - An improved method has been developed for quantitative determination of polynuclear aromatic hydrocarbons (PAHs) in pharmacopoeial paraffin and medicinal white oil samples. This new method combines 2 liquid-liquid partition and adsorption chromatography procedures with a 2-step purification on Sephadex LH 20 and liquid chromatography with fluorometric determination. Selective elution of PAHs results in absence of background fluorescence. The minimum detectable level ranges from 0.2 ppt for benzofluoranthene isomers to 200 ppt for acenaphthene. Recoveries of PAHs added at 7 ppm varied from 92.1 to 111.4%. When a variety of medicinal white oil samples were analyzed by this improved method, 27 PAHs were identified, including 11 suspected carcinogens. Their identities were confirmed by capillary gas chromatography. PMID- 1757423 TI - Analysis of organochlorine pesticide residues using simultaneous injection of two capillary columns with electron capture and electrolytic conductivity detectors. AB - A system has been developed that will allow low level screening of 31 organochlorine pesticide residues using simultaneous injection on 2 dissimilar capillary columns. An electron capture detector was attached to a DB-1701 column, and an electrolytic conductivity detector in the halogen mode was attached to a DB-5 column. Chlorinated pesticide amounts ranging from 0.05 ng for gamma-BHC to 1.5 ng for decamethrin can easily be quantitated and confirmed. The system can be used in either the column programmed mode or the isothermal column mode. Good reproducibility was obtained for injections in both modes. This system can easily be retrofitted to any gas chromatograph using on column or split/splitless injectors. PMID- 1757424 TI - Separation and determination of diesel contaminants in various fish products by capillary gas chromatography. AB - A semiquantitative capillary column gas chromatographic method is described for the determination of diesel fuel contamination in various canned seafood products. The diesel contaminants are separated from the fish sample by steam distillation, with little carry-over of interfering intrinsic materials such as fish oils. The diesel fuel is extracted from the condensate with n-hexane, and the extract is analyzed on an SPB-1 fused silica capillary column. The efficiency of recovery of diesel fuel added to canned seafood at levels of 40-400 ppt ranged from 72 to 102%. With the additional step of concentrating the hexane extract, the sensitivity of this procedure may be increased at least 10-fold. This procedure can detect the differences among diesel fuel grades No. 1, 2, and 5, and variations within diesel grade No. 2, and thus may be useful in determining the type of petroleum contaminants present in various canned fish products. PMID- 1757425 TI - GC/MIP/AED method for pesticide residue determination in fruits and vegetables. AB - This research describes the results of a gas chromatography/microwave induced plasma/atomic emission detection (GC/MIP/AED) method performed on a Hewlett Packard 5921A system for pesticide residue analysis in fruits and vegetables. A total of 6 experiments were conducted: (1) sensitivity and linearity studies for elements S, P, Cl, and N by analyzing dursban; (2) a study of instrument response to Cl concentration in pesticide molecules; (3) organochlorinated pesticide recoveries; (4) organophosphate pesticide recoveries; (5) carbamate pesticide recoveries; and (6) investigation of metallic pesticides with plictran and vendex as standards. The rank according to sensitivity and linearity was found to be as follows: S-181 greater than P-178 greater than Cl-479 greater than N-174. Instrument response to the concentration of chlorine atoms in the pesticide molecule was linear, with a correlation coefficient of 0.89. Recoveries of organochlorinated pesticides were 91.7-109.3%, with the exception of citrus, whose recovery was affected by coeluting interferences. Organophosphate recoveries were 73.2% or higher, except for the cygon oxygen analog, which degraded in the GC system under all circumstances. Carbamate recoveries were inconsistent quantitatively; however, the information generated from elements N and S were useful for qualitative confirmation of other methods, such as LC postcolumn derivatization analysis. Overall, the GC/MIP/AED method is powerful for qualitative confirmation in pesticide residue analysis. The instrument's capability of acquiring multi-elements (Cl and P) selectively and accurately is an alternative method for organochlorinated and organophosphate pesticide residue analyses. In addition, the GC/MIP/AED system is easy to use, simple to maintain, and its chromatograms can be interpreted by any chromatography analyst without much prior training. PMID- 1757426 TI - Current status of research activity in American child and adolescent psychiatry: II. A developmental analysis by age cohorts. AB - A survey designed to assess research activity was sent to 622 full-time child and adolescent psychiatric faculty at 127 academic programs. A 78.5% response rate was achieved. An examination of the responses of three age cohorts was conducted. Only about 10% of the respondents met the empirical definition of a researcher based on percentage of effort, publication, and funding. No increase in research activity was found for the youngest cohort, although significantly more younger women were holding academic appointments. Younger researchers identified psychobiological studies as a particular interest. Researchers at all ages identified a mentor program as a critical aspect of their training. PMID- 1757427 TI - The development of the woman child psychiatry researcher--a review. AB - Greater efforts should be made to recruit women into child psychiatry research. Women's tendencies to minimize their creativity and to avoid competition and criticism and women's underrepresentation and isolation in research and academia should be addressed. Nontraditional lateral tracks should be developed for women during phases of intense professional and personal demands. Mentorships, stimulating collegial relationships, and open forums at local and national levels to address these issues may encourage women's growth as child psychiatry researchers. In addition, changes for improving hiring, promoting, and facilitating career development for women are mandated. PMID- 1757428 TI - A 3-year-old boy's chronic diarrhea and unexplained death. AB - The fatal case of a three year-old boy hospitalized for chronic diarrhea is described. The diagnosis of Munchausen's by Proxy is discussed, and the approach to such cases is explored. PMID- 1757429 TI - Is divorce a major trauma? PMID- 1757430 TI - Ritual abuse of children. PMID- 1757431 TI - Will they grow out of it? PMID- 1757432 TI - Buspirone for aggression. PMID- 1757433 TI - Desipramine side-effect. PMID- 1757434 TI - Current developments in the understanding of mental retardation. Part II: Psychopathology. AB - During recent years there has been greater recognition of the impressive degree of psychiatric disturbance that affects those with mental retardation. An increasing number of systematic studies are focusing on the prevalence, risk factors, and clinical characteristics of psychiatric disturbance within this population. In addition, traditional neuropsychiatric assessment and treatment approaches are being evaluated, and new approaches are being developed. Such efforts will undoubtedly improve the ability to effectively diagnose and treat mentally retarded individuals suffering from psychiatric disorders. This paper is the second of two reviews that explore several recent developments in biological, phenomenological, and psychopathological aspects of mental retardation. PMID- 1757435 TI - Psychiatric aspects of epileptic children and adolescents. AB - Epilepsy is the most prevalent neurological disorder of childhood and adolescence and a very heterogenous disease with a diverse course of illness. It may be a benign disease for the majority of children and adolescents, who recover spontaneously or are managed well medically; however, a sizeable group of children and adolescents with epilepsy, at least one-third, do manifest various difficulties--seizure control, academic, emotional, behavioral, and family problems. As a group, they have a much higher rate of psychiatric disorder than healthy children and children with other chronic illnesses. This review is undertaken to summarize the literature on epilepsy in children and adolescents, especially with respect to epidemiology, developmental and psychiatric problems, and psychiatric treatment issues. PMID- 1757436 TI - Behavioral profile and social competence in temporal lobe epilepsy of adolescence. AB - A group of 26 adolescents with temporal lobe epilepsy was compared with a matched control group of 26 adolescents with chronic bronchial asthma as well as with a group of 90 healthy adolescents, using the social competence measure and the behavior profile of the Child Behavior Checklist. Both chronically ill groups exhibited more social and behavioral problems than the healthy adolescents but were similar to each other on the social and behavioral profiles. The one area in which the temporal lobe epilepsy and asthmatic groups differed from one another was that of "schizoid" psychopathology in male subjects. PMID- 1757437 TI - Middle childhood onset of interictal psychosis. AB - The authors describe three children (mean age = 7.8 years) with complex partial epilepsy, left temporal lobe involvement, and interictal schizophrenia-like psychosis. As described in adults with complex partial epilepsy, these children met DSM-III criteria for schizophrenia, their affect was intact, and they demonstrated no negative signs of schizophrenia. Unlike adult epileptic patients, these children demonstrated psychotic symptomatology despite inadequate seizure control and after a short latency period. The possible role of early onset seizures, temporal lobe lesions, and kindling on the developing brain are discussed. PMID- 1757438 TI - Disturbances of affect expression in failure-to-thrive. AB - Positive and negative affects were assessed in 28 6- to 36-month-old children with failure-to-thrive and 14 normally growing children in feeding and nonfeeding situations. The roles of malnutrition and severity of organic effects also were examined. Failure-to-thrive children expressed less positive affect in the feeding and nonfeeding situations and more negative affect in feeding than normally growing children. Among failure-to-thrive children, the presence of both acute and chronic malnutrition was associated with heightened negative affect during feeding, whereas the degree of organic contribution had no effect. These results, if replicated, may have implications for clinical assessment and are discussed in terms of current theories of failure-to-thrive. PMID- 1757439 TI - Parental distress and social interaction in families with children with inflammatory bowel disease. AB - Twenty families who had children with inflammatory bowel disease (IBD) and 20 comparison families with healthy children were studied concerning parental distress and social interaction. The mothers in the IBD group scored very high on parental distress, whereas the fathers did not differ from the comparison group. Both parents in the IBD group reported significantly lower scores on a social support scale. The dimension of social integration was normal, but deeper relations and attachment were negatively affected among parents in the IBD group. The mental health of the children with IBD correlated with the social support, especially the qualitative aspects. PMID- 1757440 TI - Family interaction and locus of control in children and adolescents with inflammatory bowel disease. AB - This study showed that children and adolescents with inflammatory bowel disease (IBD) had a more external locus of control than did matched diabetic and healthy children. An external locus of control correlated with severity of physical illness and presence of psychiatric disorders. It also correlated significantly with family dysfunction, which was found to be more common in the IBD group than in the groups compared. Tendencies toward a tense and negative family climate were observed in the IBD families. Awareness of the interaction between physical and psychosocial factors in IBD is essential in the management of therapy. PMID- 1757441 TI - Internalizing and externalizing symptoms and attributional style in youth with diabetes. AB - The psychiatric functioning of 28 youths with insulin-dependent diabetes mellitus was examined. Measures of psychological functioning were related to age at onset, duration of diabetes, and metabolic control, as assessed by HgbAlC. Children diagnosed with insulin-dependent diabetes mellitus at a later age were considered by teachers to have more behavioral problems. Children who had better metabolic control tended to hold themselves responsible for negative events. It is worthwhile to develop interventions to teach diabetic children a realistic balance between taking appropriate responsibility for controllable negative events without taking undue blame for uncontrollable negative events associated with the disease. PMID- 1757442 TI - A controlled study of psychoanalytic treatment of brittle diabetes. AB - The study compared two equivalent groups of 11 diabetic children with grossly abnormal blood glucose profiles necessitating repeated admissions to a hospital. Patients in the treatment group were offered an intensive inpatient treatment program including psychoanalytic psychotherapy three to four times a week, which took place on the hospital ward and lasted an average of 15 weeks. The intervention was highly effective in improving the diabetic control of the children, and this was maintained at a 1 year follow-up. Patients in the comparison group, who were offered only inpatient medical intervention, returned to their prehospitalization level of metabolic control within a period of 3 months from discharge. PMID- 1757443 TI - Malignant memories: PTSD in children and adults after a school shooting. AB - Sixty-four children and 66 adults were screened for post-traumatic stress disorder 6 to 14 months after a school shooting. Although there were no differences in overall frequencies of DSM-III-R diagnoses or cluster endorsements, there were developmental influences. Post-traumatic stress disorder was associated more with emotional states recalled from the disaster than with proximity. Emotional states mediated the formation of malignant memories leading to symptomatology, suggesting that postdisaster intervention be offered on the basis of degree of emotional reaction as well as proximity. PMID- 1757444 TI - Children and disaster: age, gender, and parental effects on PTSD symptoms. AB - Psychiatric reports of 179 children aged 2 to 15 who were exposed to the Buffalo Creek dam collapse in 1972 were rated for post-traumatic stress disorder (PTSD) symptoms 2 years after the disaster. Age and gender effects and the impact of the level of exposure and parental functioning were examined according to a conceptual model addressing factors contributing to adaptation to a traumatic event. Results showed fewer PTSD symptoms in the youngest age group and higher symptom levels for girls than boys. Approximately 37% of the children were given a "probable" diagnosis of PTSD. Multiple regression analysis showed that life threat, gender, parental psychopathology, and an irritable and/or depressed family atmosphere all contributed to the prediction of PTSD symptomatology in the children. PMID- 1757445 TI - Stress responses after pediatric bone marrow transplantation: preliminary results of a prospective longitudinal study. AB - This paper reports the preliminary findings of a longitudinal prospective study of young children undergoing bone marrow transplantation. Symptoms of post traumatic stress were seen in these children up to 12 months after transplant. The bone marrow transplantation survivors demonstrated more denial and avoidance and fewer arousal symptoms than has been noted in children traumatized by a violent life threat, such as a sniper attack. These data suggest the use of post traumatic stress as a model in understanding some of the symptoms of pediatric bone marrow transplantation survivors and may be applicable to other children exposed to the double life threat of serious illness and intensive medical intervention. PMID- 1757446 TI - Family dysfunction and alcohol and drug use in adolescent psychiatric inpatients. AB - This report examines the relationship between family functioning and substance abuse in adolescent psychiatric inpatients. The adolescents, who had been hospitalized after acute psychiatric crises, provided reports of drug and alcohol use, intoxication-related problems, and family functioning during the 4 months preceding hospitalization. Greater degrees of family dysfunction in the areas of affective responsiveness and role functioning were associated with higher levels of substance abuse. When age, sex, and diagnosis were controlled for, family dysfunction in these areas was still significantly associated with alcohol consumption but not with drug use or intoxication-related problems. Implications for treatment are discussed. PMID- 1757447 TI - Characteristics and outcome of hospitalized adolescent girls with conduct disorder. AB - Fifty-five adolescent girls with conduct disorder from a psychiatric hospital were examined with a structured interview schedule and then reevaluated 2 to 4 years later. The majority also had depressive or anxiety disorders. The criteria used for conduct disorder were less weighted toward violent crime and differed from the criteria in DSM-III-R. Their outcome was poor; 6% had died a violent death, the majority had dropped out of school, one-third were pregnant before the age of 17, half were rearrested, and many suffered traumatic injuries. Diagnoses of depression or anxiety disorders at the index admission were not associated with a better outcome. PMID- 1757448 TI - Aggressive behavior in youth: characteristics, outcome, and psychiatric diagnoses. AB - This study evaluated the characteristics and outcome of a group of children and adolescents treated in day hospital and inpatient settings. Severe aggressive/destructive behavior was present in about one-third of the sample and was more common in boys, in children and adolescents with history of parental substance abuse, and in those with a concurrent diagnosis of conduct disorder. Although both an admission diagnosis of conduct disorder and aggressive/destructive behavior as a preadmission variable predicted poor outcome, aggressive/destructive behavior was the more important of the two. Aggressive/destructive behavior in association with conduct disorder seems to confer an especially poor prognosis in hospital-treated youth. PMID- 1757449 TI - Diagnostic predictors of treatment patterns in a cohort of adolescents. AB - Data on 776 American adolescents studied longitudinally were used to show treatment patterns related to psychiatric disorders. When DSM-III-R diagnoses based on mother and youth Diagnostic Interview Schedule for Children interviews were used prospectively to determine subsequent treatment seeking, it was found that consultation with mental health specialists, but not with pediatricians or general practitioners, was elevated in those with disorders. The specific diagnoses most associated with treatment seeking were conduct disorder and oppositional/defiant disorder. No compensation for differences in mental health service usage between children with internalizing disorders and those with externalizing disorders in the form of help from informal or other professional sources was present. PMID- 1757450 TI - Predictors of length of stay of psychiatric adolescent inpatients. AB - This study reviewed 158 consecutive admissions to an inpatient adolescent psychiatric service for factors that determine length of hospitalization. Variables associated with length of stay included diagnostic category and the treatment variables of number and type of psychotropic medications prescribed. Patients with disruptive behavior disorders had the shortest hospitalizations, those with anxiety and affective disorders had stays of intermediate length, and patients with psychotic/organic disorders had the longest hospitalizations. Treatment with lithium, neuroleptics, or tricyclic antidepressants was associated with longer stays. Demographic variables and variables describing the social and family situation or level of dangerousness were not significantly associated with length of hospitalization. PMID- 1757451 TI - Paranoid and aggressive behavior in two obsessive-compulsive adolescents treated with clomipramine. AB - Obsessive-compulsive disorder is increasingly recognized in patients of different age groups. Serotonergic agents, such as clomipramine, have been recently found to be useful in the management of this condition. However, unexpected side effects, such as dysphoria, aggressiveness, and paranoid ideation, may occur with therapeutic doses of this compound, as evidenced in the cases of two male adolescents presented here. Possible pathogenetic factors, involving serotonin and serotonin-receptor abnormalities are discussed. Management of these side effects is based on adequate dose reduction and monitorization. PMID- 1757452 TI - Treatment of social phobia with drugs other than benzodiazepines. AB - Social phobia is emerging as an important cause of psychiatric morbidity. Reasons for this are described, as are clinical issues of importance to social phobia, including the extensive associated distress and disability. The use of phenelzine, atenolol, buspirone, fluoxetine, and moclobemide are described. Diagnostic and transcultural aspects of social phobia are described. PMID- 1757453 TI - Long-term treatment of social phobia with clonazepam. AB - Twenty-six socially phobic outpatients were treated with clonazepam for the relief of symptoms. At evaluation, which took place after an average of 11.3 months of continuous treatment, 22 (84.6%) patients showed good improvement and 4 (14.4%) showed no improvement or were not recovered. The dose declined over time, from a peak mean of 2.1 mg/day to a mean of 0.94 mg/day at follow-up. Side effects are described, along with individual case descriptions that illustrate important aspects of the use of benzodiazepines for the treatment of social phobia. PMID- 1757454 TI - Phenomenology and neurobiology of social phobia: comparison with panic disorder. AB - Like panic disorder, social phobia is a common, frequently severe, anxiety disorder that can cause significant work and social impairment. Unlike panic disorder, social phobia has only recently begun to undergo neurobiologic study and to receive pharmacotherapeutic attention. There is a high comorbidity between social phobia and panic disorder; however, many differences exist--including age at onset, gender distribution, contextual framework of anxiety, help-seeking and help-avoidance behavior, quality of sleep and sleep patterns, caffeine and lactate sensitivity, and, most probably, pharmacologic responses. Social phobia can now be included among the growing number of anxiety disorders that respond to pharmacotherapy. PMID- 1757455 TI - Levels of urinary free cortisol in social phobia. AB - Levels of urinary free cortisol were measured in 10 patients with social phobias and in 15 age- and sex-matched normal controls. No differences were found either in cortisol levels or in the ratio of free cortisol to creatinine. These nonsignificant differences between groups do not necessarily rule out the possibility that the hypothalamic-pituitary-adrenal axis may be altered in individuals with social phobia. PMID- 1757456 TI - Social phobia: the Anxiety Disorders Associated of America helps raise the veil of ignorance. AB - Social phobias affect some 2.4 million American adults, and more than 5 million can expect to develop a social phobia during their lifetime. Despite their prevalence, social phobias have been virtually ignored until this past decade. The Anxiety Disorders Association of America (ADAA) was founded in 1980 to promote awareness among professionals and the public of anxiety disorders. This paper outlines the objectives of ADAA and its programs, including the Self-Help Group Network, helpful publications, and its partnership with psychiatrists and patients. The benefits of self-help programs to persons with social phobias are illustrated, including the role played by the clinician in evaluation and referral. The ADAA program for the 1990s focuses on the education of all health professionals and the creation of awareness of economic costs of undiagnosed anxiety disorders. PMID- 1757457 TI - The Brief Social Phobia Scale. AB - An observer measure of social phobic symptoms, referred to as the Brief Social Phobia Scale, consists of 11 items, 7 evaluating commonly feared or avoided situations and 4 additional items measuring autonomic distress. Symptoms represented by the scale items are found frequently in social phobia, and the instrument demonstrates acceptable interrater and test-retest reliability, internal consistency, concurrent validity against other measures of social phobia, and the ability of patients to change as a result of treatment. It can also detect differences between active treatment and placebo treatment. A comparison of the sensitivity of this scale with other scales in detection of size of effect also is presented. PMID- 1757458 TI - Behavioral inhibition in children: a possible precursor to panic disorder or social phobia. AB - A biological-environmental interaction currently provides the best explanation of an anxiety disorder's evolution. In this sense, anxiety disorders are like other medical disorders for which a person may have a predisposition. Our knowledge of the evolution of anxiety disorders would be enhanced by the ability to identify those persons predisposed to anxiety and to identify such "proneness" before an anxiety disorder emerges in adulthood. We discuss the developmental aspects of panic disorder and social phobia, in particular findings suggesting that behavioral inhibition in children may be a precursor to phobic disorders in adults. Only longitudinal studies will resolve whether childhood response patterns are specifically linked to the risk of developing anxiety disorders or other psychopathology across the life cycle. In the interim, we suggest some guidelines for parents and clinicians to meet the unique needs of the inhibited child. PMID- 1757459 TI - Characterization of the immature secretory granule, an intermediate in granule biogenesis. AB - The events in the biogenesis of secretory granules after the budding of a dense cored vesicle from the trans-Golgi network (TGN) were investigated in the neuroendocrine cell line PC12, using sulfate-labeled secretogranin II as a marker. The TGN-derived dense-cored vesicles, which we refer to as immature secretory granules, were found to be obligatory organellar intermediates in the biogenesis of the mature secretory granules which accumulate in the cell. Immature secretory granules were converted to mature secretory granules with a half-time of approximately 45 min. This conversion entailed an increase in their size, implying that the maturation of secretory granules includes a fusion event involving immature secretory granules. Pulse-chase labelling of PC12 cells followed by stimulation with high K+, which causes the release of secretogranin II, showed that not only mature, but also immature secretory granules were capable of undergoing regulated exocytosis. The kinetics of secretion of secretogranin II, as well as those of a constitutively secreted heparan sulfate proteoglycan, were reduced by treatment of PC12 cells with nocodazole, suggesting that both secretory granules and constitutive secretory vesicles are transported to the plasma membrane along microtubules. Our results imply that certain membrane proteins, e.g., those involved in the fusion of post-TGN vesicles with the plasma membrane, are sorted upon exit from the TGN, whereas other membrane proteins, e.g., those involved in the interaction of post-TGN vesicles with the cytoskeleton, may not be sorted. PMID- 1757460 TI - Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network. AB - Regulated secretory proteins are thought to be sorted in the trans-Golgi network (TGN) via selective aggregation. The factors responsible for this aggregation are unknown. We show here that two widespread regulated secretory proteins, chromogranin B and secretogranin II (granins), remain in an aggregated state when TGN vesicles from neuroendocrine cells (PC12) are permeabilized at pH 6.4 in 1-10 mM calcium, conditions believed to exist in this compartment. Permeabilization of immature secretory granules under these conditions allowed the recovery of electron dense cores. The granin aggregates in the TGN largely excluded glycosaminoglycan chains which served as constitutively secreted bulk flow markers. The low pH, high calcium milieu was sufficient to induce granin aggregation in the RER. In the TGN of pituitary GH4C1 cells, the proportion of granins conserved as aggregates was higher upon hormonal treatment known to increase secretory granule formation. Our data suggest that a decrease in pH and an increase in calcium are sufficient to trigger the selective aggregation of the granins in the TGN, segregating them from constitutive secretory proteins. PMID- 1757461 TI - Isolation, characterization, and expression of cDNAs encoding murine alpha mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans. AB - Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase, EC 3.2.1.114) catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures. We have isolated overlapping clones from a murine cDNA library encoding the full length alpha-mannosidase II open reading frame and most of the 5' and 3' untranslated region. The coding sequence predicts a type II transmembrane protein with a short cytoplasmic tail (five amino acids), a single transmembrane domain (21 amino acids), and a large COOH-terminal catalytic domain (1,124 amino acids). This domain organization which is shared with the Golgi glycosyl-transferases suggests that the common structural motifs may have a functional role in Golgi enzyme function or localization. Three sets of polyadenylated clones were isolated extending 3' beyond the open reading frame by as much as 2,543 bp. Northern blots suggest that these polyadenylated clones totaling 6.1 kb in length correspond to minor message species smaller than the full length message. The largest and predominant message on Northern blots (7.5 kb) presumably extends another approximately 1.4-kb downstream beyond the longest of the isolated clones. Transient expression of the alpha-mannosidase II cDNA in COS cells resulted in 8-12-fold overexpression of enzyme activity, and the appearance of cross-reactive material in a perinuclear membrane array consistent with a Golgi localization. A region within the catalytic domain of the alpha mannosidase II open reading frame bears a strong similarity to a corresponding sequence in the rat liver endoplasmic reticulum alpha-mannosidase and the vacuolar alpha-mannosidase of Saccharomyces cerevisiae. Partial human alpha mannosidase II cDNA clones were also isolated and the gene was localized to human chromosome 5. PMID- 1757462 TI - Insulin receptors internalize by a rapid, saturable pathway requiring receptor autophosphorylation and an intact juxtamembrane region. AB - The effect of receptor occupancy on insulin receptor endocytosis was examined in CHO cells expressing normal human insulin receptors (CHO/IR), autophosphorylation and internalization-deficient receptors (CHO/IRA1018), and receptors which undergo autophosphorylation but lack a sequence required for internalization (CHO/IR delta 960). The rate of [125I]insulin internalization in CHO/IR cells at 37 degrees C was rapid at physiological concentrations, but decreased markedly in the presence of increasing unlabeled insulin (ED50 = 1-3 nM insulin, or 75,000 occupied receptors/cell). In contrast, [125I]insulin internalization by CHO/IRA1018 and CHO/IR delta 960 cells was slow and was not inhibited by unlabeled insulin. At saturating insulin concentrations, the rate of internalization by wild-type and mutant receptors was similar. Moreover, depletion of intracellular potassium, which has been shown to disrupt coated pit formation, inhibited the rapid internalization of [125I]insulin at physiological insulin concentrations by CHO/IR cells, but had little or no effect on [125I]insulin uptake by CHO/IR delta 960 and CHO/IRA1018 cells or wild-type cells at high insulin concentrations. These data suggest that the insulin-stimulated entry of the insulin receptor into a rapid, coated pit-mediated internalization pathway is saturable and requires receptor autophosphorylation and an intact juxtamembrane region. Furthermore, CHO cells also contain a constitutive nonsaturable pathway which does not require receptor autophosphorylation or an intact juxtamembrane region; this second pathway is unaffected by depletion of intracellular potassium, and therefore may be independent of coated pits. Our data suggest that the ligand-stimulated internalization of the insulin receptor may require specific saturable interactions between the receptor and components of the endocytic system. PMID- 1757463 TI - An endogenous MDCK lysosomal membrane glycoprotein is targeted basolaterally before delivery to lysosomes. AB - Using surface immunoprecipitation at 37 degrees C to "catch" the transient apical or basolateral appearance of an endogenous MDCK lysosomal membrane glycoprotein, the AC17 antigen, we demonstrate that the bulk of newly synthesized AC17 antigen is polarly targeted from the Golgi apparatus to the basolateral plasma membrane or early endosomes and is then transported to lysosomes via the endocytic pathway. The AC17 antigen exhibits very similar properties to members of the family of lysosomal-associated membrane glycoproteins (LAMPs). Parallel studies of an avian LAMP, LEP100, transfected into MDCK cells revealed colocalization of the two proteins to lysosomes, identical biosynthetic and degradation rates, and similar low levels of steady-state expression on both the apical (0.8%) and basolateral (2.1%) membranes. After treatment of the cells with chloroquine, newly synthesized AC17 antigen, while still initially targeted basolaterally, appears stably in both the apical and basolateral domains, consistent with the depletion of the AC17 antigen from lysosomes and its recycling in a nonpolar fashion to the cell surface. PMID- 1757464 TI - Protein folding causes an arrest of preprotein translocation into mitochondria in vivo. AB - With vital yeast cells, a hybrid protein consisting of the amino-terminal third of the precursor to cytochrome b2 and of the entire dihydrofolate reductase was arrested on the import pathway into mitochondria. Accumulation of the protein in the mitochondrial membranes was achieved by inducing a stable tertiary structure of the dihydrofolate reductase domain. Thereby, three salient features of mitochondrial protein uptake in vivo were demonstrated: its posttranslational character; the requirement for unfolding of precursors; and import through translocation contact sites. The permanent occupation of translocation sites by the fusion protein inhibited the import of other precursors; it did, however, not lead to leakage of mitochondrial ions, implying the existence of a channel that is sealed around the membrane spanning polypeptide segment. PMID- 1757465 TI - Characterization of actin filament severing by actophorin from Acanthamoeba castellanii. AB - Actophorin is an abundant 15-kD actinbinding protein from Acanthamoeba that is thought to form a nonpolymerizable complex with actin monomers and also to reduce the viscosity of polymerized actin by severing filaments (Cooper et al., 1986. J. Biol. Chem. 261:477-485). Homologous proteins have been identified in sea urchin, chicken, and mammalian tissues. Chemical crosslinking produces a 1:1 covalent complex of actin and actophorin. Actophorin and profilin compete for crosslinking to actin monomers. The influence of actophorin on the steady-state actin polymer concentration gave a Kd of 0.2 microM for the complex of actophorin with actin monomers. Several new lines of evidence, including assays for actin filament ends by elongation rate and depolymerization rate, show that actophorin severs actin filaments both at steady state and during spontaneous polymerization. This is confirmed by direct observation in the light microscope and by showing that the effects of actophorin on the low shear viscosity of polymerized actin cannot be explained by monomer sequestration. The severing activity of actophorin is strongly inhibited by stoichiometric concentrations of phalloidin or millimolar concentrations of inorganic phosphate. PMID- 1757466 TI - The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin. AB - The actin filament severing protein, Acanthamoeba actophorin, decreases the viscosity of actin filaments, but increases the stiffness and viscosity of mixtures of actin filaments and the crosslinking protein alpha-actinin. The explanation of this paradox is that in the presence of both the severing protein and crosslinker the actin filaments aggregate into an interlocking meshwork of bundles large enough to be visualized by light microscopy. The size of these bundles depends on the size of the containing vessel. The actin filaments in these bundles are tightly packed in some areas while in others they are more disperse. The bundles form a continuous reticulum that fills the container, since the filaments from a particular bundle may interdigitate with filaments from other bundles at points where they intersect. The same phenomena are seen when rabbit muscle aldolase rather than alpha-actinin is used as the crosslinker. We propose that actophorin promotes bundling by shortening the actin filaments enough to allow them to rotate into positions favorable for lateral interactions with each other via alpha-actinin. The network of bundles is more rigid and less thixotropic than the corresponding network of single actin filaments linked by alpha-actinin. One explanation may be that alpha-actinin (or aldolase) normally in rapid equilibria with actin filaments may become trapped between the filaments increasing the effective concentration of the crosslinker. PMID- 1757467 TI - Uncoupling of Chlamydomonas flagellar gene expression and outgrowth from flagellar excision by manipulation of Ca2+. AB - Chlamydomonas cells respond to certain environmental stimuli by shedding their flagella. Flagellar loss induces a rapid, transient increase in expression of a specific set of genes encoding flagellar proteins, and assembly of a new flagellar pair. While flagellar gene expression and initiation of flagellar outgrowth are normally tightly coupled to flagellar excision, our results demonstrate that these processes can be uncoupled by manipulating Ca2+ levels or calmodulin activity. In our experiments, wild-type cells were stimulated to excise their flagella using mechanical shearing, and at times after deflagellation, flagellar lengths were measured and flagellar mRNA abundance changes were determined by S1 nuclease protection analysis. When extracellular Ca2+ was lowered by addition of EGTA to cultures before excision, flagellar mRNA abundance changes and flagellar outgrowth were temporally uncoupled from flagellar excision. When extracellular Ca2+ was lowered immediately after excision or when calmodulin activity was inhibited with W-7, flagellar outgrowth was uncoupled from flagellar excision and flagellar mRNA abundance changes. Whenever events in the process of flagellar regeneration were temporally uncoupled, the magnitude of the flagellar mRNA abundance change was reduced. These results suggest that flagellar gene expression may be regulated by multiple signals generated from these events, and implicate Ca2+ as a factor in the mechanisms controlling flagellar regeneration. PMID- 1757468 TI - Dystrophin-associated proteins are greatly reduced in skeletal muscle from mdx mice. AB - Dystrophin, the protein product of the human Duchenne muscular dystrophy gene, exists in skeletal muscle as a large oligomeric complex that contains four glycoproteins of 156, 50, 43, and 35 kD and a protein of 59 kD. Here, we investigated the relative abundance of each of the components of the dystrophin glycoprotein complex in skeletal muscle from normal and mdx mice, which are missing dystrophin. Immunoblot analysis using total muscle membranes from control and mdx mice of ages 1 d to 30 wk found that all of the dystrophin-associated proteins were greatly reduced (80-90%) in mdx mouse skeletal muscle. The specificity of the loss of the dystrophin-associated glycoproteins was demonstrated by the finding that the major glycoprotein composition of skeletal muscle membranes from normal and mdx mice was identical. Furthermore, skeletal muscle membranes from the dystrophic dy/dy mouse exhibited a normal density of dystrophin and dystrophin-associated proteins. Immunofluorescence microscopy confirmed the results from the immunoblot analysis and showed a drastically reduced density of dystrophin-associated proteins in mdx muscle cryosections compared with normal and dy/dy mouse muscle. Therefore, our results demonstrate that all of the dystrophin-associated proteins are significantly reduced in mdx skeletal muscle and suggest that the loss of dystrophin-associated proteins is due to the absence of dystrophin and not due to secondary effects of muscle fiber degradation. PMID- 1757469 TI - Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines. AB - mAbs have been raised against different epitopes on the protein product of the DMDL gene, which is an autosomal homologue of the X-linked DMD gene for dystrophin. These antibodies provide direct evidence that DMDL protein is localized near acetylcholine receptors at neuromuscular junctions in normal and mdx mouse intercostal muscle. The primary location in tissues other than skeletal muscle is smooth muscle, especially in the vascular system, which may account for the wide tissue distribution previously demonstrated by Western blotting. The DMDL protein was undetectable in the nonjunctional sarcolemma of normal human muscle, but was observed in nonjunctional sarcolemma of Duchenne muscular dystrophy patients, where dystrophin itself is absent or greatly reduced. The expression of DMDL protein is not restricted to smooth and skeletal muscle, however, since relatively large amounts are present in transformed brain cell lines of both glial and Schwann cell origin. This contrasts with the low levels of DMDL protein in adult brain tissue. PMID- 1757470 TI - Mutagenesis of the 43-kD postsynaptic protein defines domains involved in plasma membrane targeting and AChR clustering. AB - The postsynaptic membrane of the neuromuscular junction contains a myristoylated 43-kD protein (43k) that is closely associated with the cytoplasmic face of the nicotinic acetylcholine receptor (AChR)-rich plasma membrane. Previously, we described fibroblast cell lines expressing recombinant AChRs. Transfection of these cell lines with 43k was necessary and sufficient for reorganization of AChR into discrete 43k-rich plasma membrane domains (Phillips, W. D., C. Kopta, P. Blount, P. D. Gardner, J. H. Steinbach, and J. P. Merlie. 1991. Science (Wash. DC). 251:568-570). Here we demonstrate the utility of this expression system for the study of 43k function by site-directed mutagenesis. Substitution of a termination codon for Asp254 produced a truncated (28-kD) protein that associated poorly with the cell membrane. The conversion of Gly2 to Ala2, to preclude NH2 terminal myristoylation, reduced the frequency with which 43k formed plasma membrane domains by threefold, but did not eliminate the aggregation of AChRs at these domains. Since both NH2 and COOH-termini seemed important for association of 43k with the plasma membrane, a deletion mutant was constructed in which the codon Gln15 was fused in-frame to Ile255 to create a 19-kD protein. This mutated protein formed 43k-rich plasma membrane domains at wild-type frequency, but the domains failed to aggregate AChRs, suggesting that the central part of the 43k polypeptide may be involved in AChR aggregation. Our results suggest that membrane association and AChR interactions are separable functions of the 43k molecule. PMID- 1757471 TI - Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing. AB - A transmembrane extracellular matrix receptor of the integrin family, alpha 6 beta 4, is a component of the hemidesmosome, an adhesion complex of importance in epithelial cell-connective tissue attachment (Stepp, M. A., S. Spurr-Michaud, A. Tisdale, J. Elwell, and I. K. Gipson. 1990. Proc. Natl. Acad. Sci. USA. 87:8970 8974; Jones, J. C. R., M. A. Kurpakus, H. M. Cooper, and V. Quaranta. 1991. Cell Regulation. 2:427-438). Cytosolic components of hemidesmosomes include bullous pemphigoid (BP) antigens while extracellular components include a 125-kD component of anchoring filaments (CAF) and collagen type VII-containing anchoring fibrils. We have monitored the incorporation of the alpha 6 beta 4 integrins into forming hemidesmosomes in an in vitro wound-healing explant model. In epithelial cells recently migrated from the edges of unwounded sites over bare connective tissue, alpha 6 beta 4 first appears along the entire cell surface. At this stage, these cells contain little or no cytosolic hemidesmosomal components, at least as detectable by immunofluorescence using BP autoantibodies, whereas they are already positive for laminin and CAF. At a later stage, as cells become positive for cytosolic hemidesmosome components such as BP antigens as well as collagen type VII, alpha 6 beta 4 becomes concentrated along the basal pole of the epithelial cell where it abuts the connective tissue of the explant. Polyclonal antibodies to beta 4 do not interfere with the migration of epithelial cells in the explant. However, they prevent assembly of hemidesmosomal complexes and inhibit expression of collagen type VII in cells that have migrated over wound areas. In addition, they induce disruption of established hemidesmosomes in nonmigrating cells of the unwounded area of the explant. Monoclonal antibodies to alpha 6 have a more dramatic effect, since they completely detach epithelial cells in the unwounded area of the explant. Antibodies to CAF also detach epithelial cells in unwounded areas, apparently by inducing separation between epithelium and connective tissue at the lamina lucida of the basement membrane zone. These results suggest a model whereby polarization of alpha 6 beta 4 to the basal surface of the cells, perhaps induced by a putative anchoring filament associated ligand, triggers assembly of hemidesmosome plaques. PMID- 1757472 TI - Neural cell adhesion molecule mediates contact-dependent inhibition of growth of near-diploid mouse fibroblast cell line m5S/1M. AB - A near-diploid mouse fibroblast cell line m5S/1M used in this study shows a high sensitivity to contact-dependent inhibition of growth, and the addition of EGF causes both morphological change and loss of contact-dependent inhibition of growth. The m5S/1M cell and its transformants obtained by x-ray irradiation have been used to search for the cell surface glycoproteins that are responsible for the growth regulation via cell-cell interactions. Lectin blotting analyses showed that the expression of the cell surface glycoprotein of 140 kD (140KGP) is highly sensitive to the transformation induced either by x-ray irradiation or by the EGF stimulation. We purified the 140KGP and found that it was composed of two glycoproteins. The major component of 140KGP was identified as neural cell adhesion molecule (NCAM) by amino acid sequence analyses of the peptide fragments and by the cross-reactivity with anti-NCAM mAb, clone H28.1.2.3. Monoclonal antibody against 140KGP (clone LN-10) recognizes all three isoforms of NCAM expressed on m5S/1M cell and showed that the expression of NCAM was highly sensitive to the transformation. Furthermore, the immobilized LN-10 strongly inhibited the growth of actively proliferating m5S/1M cells and the LN-10 in a soluble form showed a significant growth-stimulating effect on the confluent quiescent cultures of m5S/1M cells. The results show that NCAM plays a major role in the contact-dependent inhibition of growth of m5S/1M, and that NCAM might be involved in the regulation of cell growth during embryogenesis and formation of nervous systems. PMID- 1757473 TI - Quantitative variations in gene expression: possible role in cellular diversification and tumor progression. AB - Changes in the quantitative expression of certain genes or in the amounts of their products can quickly stimulate progression to the metastatic phenotype. This has been done experimentally by transferring dominantly acting oncogenes such as c-H-rasEJ into susceptible cells or more recently by interfering with metastasis suppressor genes. In vivo such rapid qualitative changes in dominantly acting oncogenes or suppressor genes occur only rarely, and progression to highly metastatic phenotypes is thought to occur through a process involving the slow stepwise progression of a subpopulation of neoplastic cells to more malignant states. Such slow changes can be reversible and need not involve known dominantly acting oncogenes or metastatic suppressor genes, consistent with clinical and experimental observations on naturally occurring, highly advanced metastatic tumors. An important element in the natural progression of tumors to more malignant states may be their ability to circumvent host environmental controls that regulate growth and cellular diversity. They also evolve into heterogeneous cellular phenotypes, a process that appears to mainly involve quantitative changes in gene expression but can be rapidly stimulated in cell culture by the introduction of a dominantly acting oncogene or inhibited by the introduction of a suppressor gene. The oncogenes and suppressor genes that affect malignancy may control important steps in the quantitative regulation of sets of genes that are ultimately responsible for the cellular alterations seen in adhesion receptors, cell motility responses, cell-cell communication components, degradative enzymes and their inhibitors, growth factor receptors, components that aid in escape from host surveillance mechanisms and others that are important in malignancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757474 TI - Cytokine induction in HTLV-I associated myelopathy and adult T-cell leukemia: alternate molecular mechanisms underlying retroviral pathogenesis. AB - The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing a variety of host cellular genes including many of the cytokines responsible for immune regulation and osteoclast activation. This derangement in cytokine expression may contribute to the panoply of disease states associated with HTLV-I infection such as the adult T-cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). We wished to determine if there was a correlation between the expression of an array of cytokines and the diverse clinical manifestations of ATL and HAM/TSP. Utilizing the techniques of specific mRNA amplification by the polymerase chain reaction (PCR) as well as Northern blotting, we analyzed the ex vivo mRNA expression of gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF-beta 1) in the peripheral blood of HAM/TSP and ATL patients as well as asymptomatic seropositive carriers. IFN gamma, TNF-alpha, and IL-1 beta transcripts were up-regulated in patients with HAM/TSP and seropositive carriers when compared to their levels in ATL and normal controls. In contrast, the ATL patients constitutively expressed higher levels of TGF-beta 1 mRNA than HAM/TSP and seropositive carriers. In addition, TNF-alpha and IL-1 beta serum levels were elevated in HAM/TSP, but not in ATL patients nor seropositive carriers. However, the circulating leukemic cells from ATL patients secreted increased levels of TGF-beta 1 protein into the culture medium than T cells derived from HAM/TSP patients. Collectively these results suggest that induction of IFN-gamma, TNF-alpha, and IL-1 beta in HAM/TSP may initiate an inflammatory cascade with subsequent events leading to immune mediated destruction of the central nervous system in these patients. Expression of osteoclast activators such as TNF-alpha and IL-1 beta is not associated with hypercalcemia in ATL. Finally, impaired cellular and humoral immune responses present in ATL, but not in HAM/TSP, may be related to elevated levels of TGF-beta 1 produced by the leukemic cells. These differences in retroviral-induced host cytokine expression in ATL and HAM/TSP suggest alternate roles in disease pathogenesis. PMID- 1757475 TI - Secretion of mutant leucine-specific binding proteins with internal deletions in Escherichia coli. AB - The leucine-specific binding protein, encoded by the livK gene, is located in the periplasm of E. coli. The present study is an attempt to identify intragenic regions that determine the efficiency of its secretion into the periplasm. C terminal deletions or fusions of the livK gene to trpA (encoding the alpha subunit of tryptophan synthetase) were secreted with little loss of efficiency [1]. A series of deletions was constructed at the unique Sphl site within livK, near the 5' end of the region coding for the mature protein. Between 16 and 113 amino acids were deleted in the amino-terminal one-third of the protein. A few of these deletions were located within a few amino acids of the signal sequence processing site. Deletions extending within thirteen residues of the processing site were processed and secreted more slowly than normal. Secondary structure predictions suggested that the alpha-helical core region of the signal sequence extends into the mature protein in the case of the slow processing mutants, perhaps interfering with the recognition site for leader peptidase or other secretory components. These results suggest that the conformation around the signal processing site may be a critical factor in determining the efficiency of secretion. During the course of this study, it was found that the difference in molecular weight between precursor and mature forms of some binding protein mutants, as judged by SDS-PAGE, was much greater than could be accounted for by processing of the signal sequence. This anomalous mobility on gels, however, could be eliminated by performing SDS-PAGE in the presence of 6 M urea. PMID- 1757476 TI - Evidence for an immunological and functional relationship between superoxide dismutase and a high molecular weight osteoclast plasma membrane glycoprotein. AB - Large multinucleated osteoclasts are the major cells responsible for bone breakdown and have been reported to produce high levels of superoxides which may contribute to the process of bone resorption (Key et al.: J Bone and Mineral Res 4 [suppl. 1]:S206, 1989). Osteoclasts also possess high levels of superoxide dismutase, a protective enzyme capable of converting toxic superoxides to less dtoxic H2O2 (Fridovich: J Biol Chem 264:7761-7764, 1989). The amino acid sequence of manganese and/or iron superoxide dismutase has a conserved region which exhibits substantial homology with a fragment obtained from a high molecular weight osteoclast surface marker glycoprotein which is reactive with monoclonal antibody 121F. In this report, evidence is presented substantiating immunological, biochemical, and functional similarities between the osteoclast membrane antigen recognized by the 121F monoclonal antibody and superoxide dismutase. Western blot and immunoprecipitation studies show that a monospecific polyclonal antibody generated against immunoaffinity purified antigen is cross reactive with superoxide dismutase. Both the antigen and a high molecular weight superoxide dismutase activity have been detected in osteoclast plasma membrane preparations. The levels of superoxide dismutase activity and the membrane antigen have been found to correlate in antigen depletion studies and in western blots probing osteoclasts and closely related marrow-derived giant cells. Moreover, regions of osteoclast superoxide dismutase activity identified by electrophoretic zymogram analysis have been shown by gel electrophoresis and western blots to contain the high molecular weight antigen, or complexes of the antigen with the 121F monoclonal antibody when these were premixed prior to nondenaturing electrophoresis. It is proposed that the osteoclast plasma membrane possesses a high molecular weight superoxide dismutase activity. Furthermore, it appears that this activity is associated with the osteoclast antigen recognized by the 121F monoclonal antibody. PMID- 1757477 TI - Regulation of expression of the growth-state-related genes 2F1 and 2A9 during entry of quiescent smooth muscle cells into the cell cycle. AB - Vascular smooth muscle cells (SMCs) play a key role in the development of major arteries. Furthermore, abnormal growth of vascular smooth muscle cells has been implicated in the progression of major diseases of the cardiovascular system. Here, we report detection in primary cultures of bovine vascular smooth muscle cells of mRNA for two growth-state-related genes, 2F1 and 2A9, which code for a mitochondrial ADP/ATP carrier and calcyclin, respectively, and on the characterization of their cell cycle expression. Cultures of exponentially growing smooth muscle cells were made quiescent by serum deprivation. Upon readdition of serum, cells entered the cell cycle synchronously; DNA synthesis began 12 h post-serum addition. Levels of 2F1 and 2A9 RNA were low in quiescent cells and increased between 2 and 4 h post-serum addition. No changes in the rates of transcription of the 2F1 or 2A9 genes were detected by nuclear run-off assays during the time course. Thus the regulation of changes in expression of 2F1 and 2A9 in early G1 is mediated post-transcriptionally. PMID- 1757478 TI - Developmental expression and hormonal regulation of the rat matrix Gla protein (MGP) gene in chondrogenesis and osteogenesis. AB - Matrix Gla protein (MGP), a vitamin K dependent protein, has recently been identified in many tissues. However, it is accumulated only in bone and cartilage suggesting that the expression of MGP may be related to the development and/or maintenance of the phenotypic properties of these tissues. We systematically evaluated MGP mRNA expression as a function of bone and cartilage development and also as regulated by vitamin D during growth and cellular differentiation. Three experimental models of cartilage and bone development were employed: an in vivo model for endochondral bone formation, as well as in primary cells of normal diploid rat chondrocyte and osteoblast cultures. MGP was expressed at the highest level during cartilage formation and calcification in vivo during endochondral bone formation. In chondrocyte cultures, MGP mRNA was present throughout the culture period but increased only after 3 weeks concomitantly with type I collagen mRNA. In osteoblast cultures, MGP mRNA was expressed during the proliferative period and exhibited increased expression during the period of matrix development. In contrast to osteocalcin (bone Gla protein), this increase was not dependent on mineralization but was related to the extent of differentiation associated with and potentially induced by extracellular matrix formation. During the proliferative period, type I collagen mRNA peaked and thereafter declined, while type I collagen protein steadily accumulated in the extracellular matrix. Constant MGP levels were maintained in the mineralization period of osteoblast differentiation in vitro which is consistent with the constant levels found during the osteogenic period of the in vivo system. MGP mRNA levels in both osteoblasts and chondrocytes in culture were significantly elevated by 1,25-(OH)2D3 (10(-8) M, 48 h) throughout the time course of cellular growth and differentiation. Interestingly, when MGP mRNA transcripts from vitamin D treated and untreated chondrocytes and osteoblasts were analyzed by high resolution Northern blot analysis, we observed two distinct species of MGP mRNA in the vitamin D treated chondrocyte cultures while all other cultures examined exhibited only a single MGP mRNA transcript. Primer extension analysis indicated a single transcription start site in both osteoblasts and chondrocytes with or without vitamin D treatment, suggesting that the lower molecular weight MGP message in vitamin D treated chondrocytes may be related to a modification in post-transcriptional processing. In conclusion, these results show that the selective accumulation of MGP in bone and cartilage tissues in vitro may be related to the development and/or maintenance of a collagenous matrix as reflected by increases in MGP mRNA during these periods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1757479 TI - The nuclear matrix: a heuristic model for investigating genomic organization and function in the cell nucleus. AB - Despite significant advances in deciphering the molecular events underlying genomic function, our understanding of these integrated processes inside the functioning cell nucleus has, until recently, met with only very limited success. A major conundrum has been the "layers of complexity" characteristic of all cell structure and function. To understand how the cell nucleus functions, we must also understand how the cell nucleus is put together and functions as a whole. The value of this neo-holistic approach is demonstrated by the enormous progress made in recent years in identifying a wide variety of nuclear functions associated with the nuclear matrix. In this article we summarize basic properties of in situ nuclear structure, isolated nuclear matrix systems, nuclear matrix associated functions, and DNA replication in particular. Emphasis is placed on identifying current problems and directions of research in this field and illustrating the intrinsic heuristic value of this global approach to genomic organization and function. PMID- 1757480 TI - Transcriptional regulation of basic fibroblast growth factor gene expression in capillary endothelial cells. AB - The growth of capillary endothelial cells (BCE) is an important regulatory step in the formation of capillary blood vessels. In vivo, the proliferation of these cells is stringently controlled. In vitro they can be stimulated by polypeptide growth factors, such as acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Since bFGF is synthesized and stored by vascular endothelial cells, this mitogen may play an important role in an autocrine growth regulation during angiogenesis. Here, evidence is presented for induction of the mRNA of bFGF by bFGF itself. A similar increase of bFGF mRNA was observed in response to thrombin and after treatment with phorbol ester. These results suggest that an autocrine loop may exist that may serve to modulate the mitogenic response in BCE under various physiological conditions, (e.g., wound healing and new capillary formation). PMID- 1757481 TI - Influence of dexamethasone on the vitamin D-mediated regulation of osteocalcin gene expression. AB - The influence of dexamethasone on expression of the osteocalcin gene which encodes the most abundant non-collagenous and only reported bone-specific protein was examined in ROS 17/2.8 osteosarcoma cells which express a broad spectrum of genes related to bone formation. Consistent with previous reports, quantitation of cellular osteocalcin mRNA levels by Northern blot analysis, osteocalcin gene transcription by activity of the osteocalcin gene promoter fused to a chloramphenicol acetyl-transferase (CAT) mRNA coding sequence following transfection into ROS 17/2.8 cells, and osteocalcin biosynthesis by radioimmunoassay indicate that dexamethasone in a concentration range of 10(-6) to 10(-9) M only modestly modifies basal levels of osteocalcin gene expression. However, dexamethasone significantly inhibits these parameters of the vitamin D induced upregulation of osteocalcin gene expression in both proliferating and in confluent ROS 17/2.8 cells. In this study, we observed that the extent to which abrogation of the vitamin D response occurs is dependent on basal levels of osteocalcin gene expression as reflected by a complete inhibition of the vitamin D-induced upregulation in a ROS 17/2.8K subline with low basal expression and only a partial reduction of the vitamin D stimulation in a ROS 17/2.8C subline with eightfold higher levels of basal expression. This effect of glucocorticoid appears to be at the transcriptional and post-transcriptional levels as demonstrated by a parallel decline in the cellular representation of osteocalcin mRNA, osteocalcin gene promoter activity, and osteocalcin biosynthesis. The complexity of the glucocorticoid effect on vitamin D-mediated transcriptional properties of the osteocalcin gene is indicated by persistence of sequence specific protein-DNA interactions at two principal osteocalcin gene promoter regulatory elements, the osteocalcin (CCAAT) box which modulates basal level of transcription, and the vitamin D responsive element, where vitamin D-mediated enhancement of osteocalcin gene transcription is controlled. PMID- 1757482 TI - If genes just make proteins and our proteins are the same, then why are we so different? PMID- 1757483 TI - Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci. AB - It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high level gene expression. The result of these experiments will have important consequences for random gene transfer with predictable and reproducible expression of transgenes. PMID- 1757484 TI - Modulation of chondrogenesis by the cytoskeleton and extracellular matrix. PMID- 1757485 TI - Tissue culture of human epidermal keratinocytes: a differentiating model system for gene testing and somatic gene therapy. PMID- 1757486 TI - Kinetochore function can be altered by ultraviolet microbeam irradiation without loss of the associated birefringent spindle fibre. AB - We have irradiated kinetochores of chromosomes in spermatocytes of crane flies (Nephrotoma abbreviata (Loew)) and Nephrotoma suturalis (Loew), while observing the cells using polarization microscopy. Irradiation of a kinetochore of one sex chromosome with 0.106 ergs microns-2, the minimum dose needed to stop movement, had no effect on the birefringence of the irradiated kinetochore's spindle fibre. Irradiation of the kinetochore of an autosomal half-bivalent in anaphase, with the same dose, had no effect on the birefringence of the irradiated kinetochore's spindle fibre, but nonetheless the anaphase movements of all six autosomal half bivalents were stopped, temporarily, for up to 20 min. Irradiations of the kinetochores of an autosomal half-bivalent with higher doses (0.301 ergs microns 2) caused loss of birefringence of the irradiated kinetochore's spindle fibre, and the movements of all six autosomal half-bivalents were stopped permanently. We argue that the ultraviolet microbeam differentially affects two functions of the kinetochore: (1) a 'signalling' function, and (2) microtubule attachment, with the signalling function being altered at doses lower than that of microtubule attachment. PMID- 1757487 TI - Electron-microscopic and immunochemical analysis of kinetochore microtubules after ultraviolet microbeam irradiation of kinetochores. AB - We used an ultraviolet microbeam to irradiate kinetochores of chromosomes in crane-fly spermatocytes. We used one of two doses, low (0.106 erg microns-2) or high (0.301 erg microns-2), and then studied the microtubules in those spindles using electron microscopy or immunofluorescence microscopy. After irradiation with low doses microtubules are present as usual, with normal fluorescence and in normal numbers. After irradiation with high doses microtubules are no longer associated with the irradiated kinetochore. After irradiation with either dose, non-kinetochore microtubules are in smaller numbers in the irradiated half spindle than in the non-irradiated half-spindle or in non-irradiated cells. Since irradiation with low doses alters interchromosomal 'signals', but microtubules remain attached to the kinetochore, we argue that low doses of ultraviolet light damage a signal-related function of kinetochores without altering the ability of the kinetochores to bind microtubules. PMID- 1757488 TI - Direct experimental evidence for the existence, structural basis and function of astral forces during anaphase B in vivo. AB - The existence, structural basis and function of astral forces that are active during anaphase B in the fungus, Nectria haematococca, were revealed by experiments performed on living cells. When one of the two asters of a mitotic apparatus was damaged, the entire mitotic apparatus migrated rapidly in the direction of the opposing astral forces, showing that the force that accelerated spindle pole body separation in earlier experiments is located in the asters. When a strong solution of the antimicrotubule drug, MBC, was applied at anaphase A, tubulin immunocytochemistry showed that both astral and spindle microtubules were destroyed completely in less than a minute. As a result, separation of the spindle pole bodies during anaphase B almost stopped. By contrast, disrupting only the spindle microtubules with a laser microbeam increased the rate of spindle pole body separation more than fourfold. Taken together, these two experiments show that the astral forces are microtubule-dependent. When only one of the two or three bundles of spindle microtubules was broken at very early anaphase B, most such diminished spindles elongated at a normal rate, whereas others elongated at an increased rate. This result suggests that only a critical mass or number of spindle microtubules needs be present for the rate of spindle elongation to be fully governed, and that astral forces can accelerate the elongation of a weakened or diminished spindle. PMID- 1757489 TI - Induction of partial mitosis in BHK cells by 2-aminopurine. AB - The protein kinase inhibitor 2-aminopurine (2-AP) inhibits a subset of mitotic events in BHK cells. In the presence of the drug, these cells form a bipolar spindle in mitosis, but chromatin fails to generate functioning chromosomes. Cells in 2-AP progress through a partial mitosis, in which there is no observable metaphase, anaphase or telophase events. After 12 h of exposure to 2-AP the chromatin in mitotic cells fails to condense into discrete chromosomes, and is displaced by the spindle to form 'binucleate' cells and cells containing abnormally shaped nuclei in the subsequent interphase. Other mitotic modifications of nuclei, such as nucleolar and nuclear lamina disassembly, occur normally. Centromeres in these nuclei do not become engaged in the spindle, but instead show either no association or a lateral arrangement around the spindle. Cells treated with 2-AP are not arrested in mitosis. Therefore, mitotic exit is not inhibited by the failure of these cells to progress through the latter stages of mitosis. Further, nocodazole-arrested cells quickly exit mitotic arrest when 2 AP is added. We conclude that 2-AP interferes with a specific subset of mitotic events, and that it allows cells to overcome check-points that require spindle function for mitotic progression. PMID- 1757490 TI - Biosynthesis and transport of lysosomal alpha-glucosidase in the human colon carcinoma cell line Caco-2: secretion from the apical surface. AB - The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is converted into a precursor of slightly higher Mr (112 x 10(3)) by the addition of complex oligosaccharide chains. Via an intermediate form of 95 x 10(3) Mr, this precursor is processed into a mature form of 76 x 10(3) Mr. Combination of metabolic labelling with subcellular fractionation showed that the 112 x 10(3) Mr precursor of alpha-glucosidase is transported to the lysosomes. However, the same form is secreted into the culture medium (20% of newly synthesized enzyme after 4 h of chase). Immunoprecipitation of alpha-glucosidase from culture medium derived from either the apical or basolateral site of radiolabelled Caco-2 cells, showed that 70-80% of the total amount of precursor form present in the medium is secreted from the apical membrane. Measurement of enzyme activities also showed that alpha-glucosidase, unlike other lysosomal enzymes, is mainly secreted via the apical pathway. Furthermore, immunocytochemistry showed the presence of a precursor form of alpha-glucosidase on the apical, but not the basolateral, membrane of the Caco-2 cells. We conclude that alpha-glucosidase is, unlike all other secretory proteins studied so far, secreted preferentially from the apical membrane of Caco-2 cells. PMID- 1757491 TI - The epidermal growth factor-induced migration of rat liver epithelial cells is associated with a transient inhibition of DNA synthesis. AB - Epidermal growth factor (EGF) is a potent mitogen for most cultured cells and has previously been shown to induce the migration of rat liver epithelial cells. We have now demonstrated that under migration-inducing conditions EGF does not stimulate cell proliferation, but causes instead a transient inhibition of DNA synthesis. Analysis at the single-cell level by [3H]thymidine autoradiography indicated that in 40-50% of the EGF-treated cell population the entry into S phase is delayed. The simultaneous demonstration of migration tracks by laminin immunofluorescence revealed that the transient inhibition of DNA synthesis is not restricted to the migratory cells. The effect is also observed with the stationary subpopulation and appears, therefore, to be independent of the induction of migration. The independence of both processes was further supported by showing that induction of migration by EGF proceeds undisturbed in cells blocked in S phase by aphidicolin. These results indicated that for rat liver epithelial cells the induction of migration by EGF has priority over cell proliferation. The data also emphasize the need for a time-course analysis when studying factors that stimulate or inhibit DNA synthesis or cell proliferation. PMID- 1757492 TI - Production of matrix metalloproteinase 3 (stromelysin) by cultured ovine endometrial cells. AB - Ovine endometrial cells (stromal plus epithelial) in primary culture release matrix metalloproteinase 3 (stromelysin, MMP-3), the enzyme that degrades various extracellular components including the basement membrane components collagen IV and laminin. The enzyme was detected in tissue culture medium by specific enzyme assay. A low level of MMP-3 activity was released from the cells (0.12 +/- 0.02 unit per 10(6) cells per 48 h; 1 unit degrades 1 microgram of reduced, carboxymethylated transferrin min-1 at 37 degrees C), but following stimulation by phorbol myristate acetate (PMA) a mean 4.4-fold increase in MMP-3 production was observed (to 0.53 +/- 0.13 unit per 10(6) cells per 48 h). The enzyme was released primarily in the form of its proenzyme, which could be activated in vitro by (4-aminophenyl)mercuric acetate (APMA). Stimulation of enzyme release from cells by PMA was not seen before 24 h and required PMA at a dose of 10 nM or higher. This finding was substantiated by Western blot analysis. Immunocytochemistry of cells that had been treated with PMA for 48 h, and with the ionophore, monensin, for 4 h, confirmed the potential of the endometrial cells to produce stromelysin. The release of MMP-3 from ovine endometrial cells suggests that this enzyme may have a role in assisting the passage of syncytial processes through the basement membrane during the process of implantation. PMID- 1757493 TI - Enhanced expression of fibronectin by cmd/cmd chondrocytes and its modulation by exogenously added proteoglycan. AB - Cartilage matrix deficiency (cmd/cmd) in mice is a genetic disorder associated with the failure of chondrocytes to synthesize the core protein of cartilage proteoglycan monomer (cartilage-PG). Immunohistochemical and biochemical analyses revealed enhanced accumulation of fibronectin in culture of cmd/cmd chondrocytes as well as in mutant cartilage tissue in vivo. Purified cartilage-PG, when added exogenously to a culture of cmd/cmd chondrocytes, caused a reduction in abnormal accumulation of fibronectin over several subsequent days of culturing. Using a fibronectin cDNA probe, we showed that, on the basis of total RNA, the fibronectin mRNA level was four or eight times higher in cmd/cmd chondrocytes than in the normal. The level of fibronectin mRNA in cmd/cmd cells was lowered by culturing the cells in the presence of added cartilage-PG. These findings suggest that the abnormal accumulation of fibronectin in the mutant cell culture is primarily due to elevation of fibronectin mRNA level, and that cartilage-PG in the extracellular matrix may affect the regulation of fibronectin biosynthesis at the steady-state level of mRNA. PMID- 1757494 TI - When is a centromere not a kinetochore? PMID- 1757495 TI - Ultrastructure of chromatin. II. Three-dimensional reconstruction of isolated fibers. AB - Electron-microscope tomography has been used to reconstruct isolated, negatively stained chromatin fibers from Necturus maculosus erythrocytes. Tilt series micrographs from +70 degrees to -70 degrees at 5 degrees intervals were obtained, allowing a reconstruction resolution of 3.3 nm for fibers lying parallel to the tilt axis. The fibers were found to be flattened in the plane of the carbon support, and also stained differentially according to the distance from the carbon. A number of methods of presenting the three-dimensional information were explored. Especially useful was an automatic peak search method for locating putative nucleosome positions coupled with the production of a computer-generated model. Other valuable techniques included the generation of projection stereograms and construction of solid models. A peripheral location of nucleosomes in the chromatin fiber was indicated, and helical arrangements of nucleosomes were observed over short regions. However, no long-range ordering of nucleosomes was apparent. The extent to which this lack of order may be the result of events occurring during the preparation of chromatin for electron microscopy is discussed. PMID- 1757496 TI - Histone acetylation and control of gene expression. PMID- 1757497 TI - Adipocytic cells cultured from marrow have osteogenic potential. AB - Stromal colonies with fibroblastic morphology grown from rabbit marrow cells in culture supplemented with foetal calf serum. In this study the same marrow cells cultured with autologous rabbit plasma and hydrocortisone form colonies of a single lineage that express the adipocytic phenotype. A comparison of the potential for differentiation of cloned cell populations grown from fibroblastic and adipocytic colonies has been made using an in vivo diffusion chamber assay. The adipocytic colonies differentiated and grew to a limited size in medium with rabbit plasma and hydrocortisone, but attempts to isolate them and expand them in this medium failed. When the serum supplement was changed to foetal calf serum at day 10 the cells in the adipocytic colonies acquired a less differentiated morphology, there was a large increase in colony growth and cells were produced in sufficient numbers for the diffusion chamber assay. Thirty one fibroblastic colonies and twenty one adipocytic colonies were isolated either by limiting dilution or ring cloning and then expanded. Of these, eleven fibroblastic and eight adipocytic colonies provided enough cells (2 x 10(5) to 2 x 10(6] for implantation and culture in the chambers. Four of the eleven fibroblastic and three of the eight adipocytic colonies formed an osteogenic tissue in the chambers. It was concluded that cells that have differentiated in an adipocytic direction are able to revert to a more proliferative stage and subsequently to differentiate along the osteogenic pathway. Adipocytic and fibroblastic cells cultured in vitro from marrow have, with osteogenic cells, a common precursor in adult marrow. PMID- 1757498 TI - Expression of a divalent cation-dependent erythroblast adhesion receptor by stromal macrophages from murine bone marrow. AB - Stromal macrophages in haemopoietic organs express novel surface receptors that are implicated in trophic interactions with developing blood cells. Macrophages isolated from foetal liver bind erythroblasts (Eb) by a divalent cation-dependent receptor (EbR), whereas stromal macrophages in adult bone marrow and lymphoid organs express a lectin-like receptor, sialoadhesin, which interacts with sialylated structures on sheep erythrocytes and murine haemopoietic cells. In order to learn more about the regulation of these haemagglutinins, we examined binding of Eb by stromal macrophages that had been isolated from adult murine tissues or generated in Dexter-type cultures of bone marrow. Macrophages were purified from bone marrow by collagenase digestion, adherence to a substratum and detachment of clustered haemopoietic cells, and tested for their ability to bind Eb from foetal liver or anaemic adult spleen. Freshly isolated bone marrow macrophages bound Eb mainly by a divalent cation-dependent activity that was not inhibited by neuraminidase treatment of Eb or by specific anti-sialoadhesin monoclonal antibodies, although these macrophages express sialoadhesin and Eb bear a potential ligand for this receptor. Macrophages obtained by digestion from other adult lymphoid tissues also bound Eb by a divalent cation-dependent activity, whereas blood monocytes and lavaged peritoneal macrophages failed to do so. Peritoneal macrophages could be induced to express high levels of sialoadhesin by cultivation in homologous mouse serum, but such macrophages did not acquire sialoadhesin-independent EbR activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757499 TI - Production of heparan sulphate proteoglycans by human bone marrow stromal cells. AB - Haemopoietic progenitors from human bone marrow bind strongly to human marrow stromal cell cultures but the interaction only occurs if the stromal cells are maintained in methyl prednisolone. Heparan sulphate has been implicated in this interaction and in the binding of haemopoietic cell growth factors. In the present study we have compared the molecular structures of the heparan sulphate proteoglycans, metabolically labelled with [35S]sulphate, produced by methyl prednisolone-treated and untreated human marrow stromal cells in vitro. [35S]proteoglycans were examined in the cell layers (extracted with 1% (v/v) Triton X-100 in 6 M urea) and in the culture medium. Fractionation of proteoglycans by ion-exchange chromatography indicated that the heparan sulphate produced by the treated cultures eluted at a higher NaCl concentration than the counterpart from untreated cells. The heparan sulphate appeared to be mainly expressed on the cell surface, since it was efficiently extracted by treatment with dilute trypsin (50 micrograms ml-1 for 10 min). All cultures contained two heparan sulphate proteoglycan species, the major component eluted from a Sepharose CL-4B column with a median Kav of 0.33 and apparently contained an average of only one heparan sulphate chain. Small quantities of a larger proteoglycan, which was eluted in the void volume from the CL-4B column, was also detected, mainly in the cell layer extracts. The molecular structure of the heparan sulphate chains was analysed by oligosaccharide mapping, following specific enzymic depolymerisation, and separation of breakdown products by gradient PAGE. The maps revealed significant differences in overall enzyme susceptibilities and sulphation patterns of polysaccharides produced by methyl prednisolone-treated and untreated cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757500 TI - Low density lipoproteins bound to Schistosoma mansoni do not alter the rapid lateral diffusion or shedding of lipids in the outer surface membrane. AB - Schistosomula of Schistosoma mansoni bind human low density lipoproteins (LDL) in a concentration-dependent and saturable manner. The bound LDL could provide phospholipids and sterol to the worm, which cannot synthesize sterol de novo and lacks acyl chain-modifying capability. Here we have used three phospholipid analogues to explore the effect of LDL binding on the parasite's outer tegumental membrane, i.e. the outer of the two membranes that cover its surface syncytium. Fluorescein phosphatidylethanolamine (Fl-PE) and rhodamine phosphatidylethanolamine (Rh-PE) bound to the parasite in a saturable manner and, as shown by fluorescence microscopy, were confined to the surface. Fl-PE fluorescence was completely quenched by Trypan Blue and Fl-PE was lost from the surface following single exponential decay kinetics (t1/2 = 12 h), further suggesting that the probe was confined to the outer membrane. 1,1'-Dioctadecyl 3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-C18(3); DiI) did not bind saturably and was seen in both the surface and the internal parasite membranes. Fluorescence photobleaching recovery was used to measure the lateral mobility of Fl-PE in the outer membrane. The lateral diffusion coefficient of Fl-PE was approximately 10(-7) cm2s-1. The fractional mobility of Fl-PE was 85% when measured using a laser beam of radius 1.8 microns and 45% using a beam of radius 4.3 microns. These measurements suggest that the outer membrane is composed of micron-scale liquid crystalline-phase lipid domains that lack significant amounts of transmembrane proteins. LDL binding to the parasite surface did not alter the lateral mobility of Fl-PE or the rate of loss of either Fl-PE or Rh-PE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757501 TI - Monoclonal antibodies to Leishmania mexicana promastigote antigens. II. Cellular localization of antigens in promastigotes and infected macrophages. AB - In the accompanying paper by Ilg et al., it was shown that Leishmania mexicana promastigotes covalently modify a secreted acid phosphatase and other proteins by carbohydrate epitopes characteristic for lipophosphoglycan (LPG). In this study, the reaction of the anti-LPG monoclonal antibodies (mAbs AP3 and L7.25) and of mAb L3.13, an antibody directed against an epitope present on the secreted acid phosphatase but not on LPG, with promastigotes and infected peritoneal macrophages is studied by immunofluorescence and immunoelectron microscopy. AP3 labels the surface, the flagellar pocket and intracellular structures in promastigotes, while L3.13 reacts predominantly with an antigen located in the flagellar pocket. Early after infection with promastigotes, but not amastigotes, AP3 or L7.25 transiently label epitopes at the surface of live macrophages. No L3.13-reactive material is detected at the surface of infected macrophages. In permeabilized, infected macrophages, AP3 heavily labels the surface of amastigotes and the lumen of the parasitophorous vacuole, while L3.13 reveals antigen in the flagellar pocket, intracellular vesicles of amastigotes, and components in the lumen of the parasitophorous vacuole. Possible mechanistic implications for Leishmania-macrophage interaction raised by these findings are discussed. PMID- 1757502 TI - Photoreception of Paramecium cilia: localization of photosensitivity and binding with anti-frog-rhodopsin IgG. AB - Paramecium bursaria is photosensitive and accumulates in a lighted area. The cells can be deciliated by a brief suspension in dilute ethanol. Both intact and deciliated cells showed depolarization in response to light stimulation by a step increase from dark to above 0.7 mW cm-2 (550 nm). On the other hand, after a step increase to below 0.4 mW cm-1, intact cells showed hyperpolarization, while the deciliated cells showed no change in membrane potential. This difference in membrane potential response between ciliated and deciliated cells suggests that both somatic and ciliary structures are photosensitive. In our search for the photoreceptive molecules, a polyclonal antibody induced in rabbits against frog rhodopsin was found to cross-react with a 63x10(3) Mr protein of P. bursaria, by immunoelectrophoresis. Immunocytochemical studies showed that the antibody labeling was localized on both the ciliary and the somatic membranes. These results raise the possibility that P. bursaria may contain a rhodopsin-like protein as a photoreceptor molecule. PMID- 1757503 TI - Cell guidance by ultrafine topography in vitro. AB - Laser holography and microelectronic fabrication techniques have been employed to make grating surfaces in fused quartz with ultrafine period (260 nm) in an attempt to mimic the topography of aligned fibrillar extracellular matrix (ECM), which, in the past, has been shown to affect the behaviour of cells in vitro and in vivo. The alignment of BHK cells, MDCK cells and chick embryo cerebral neurones on 260 nm period grating surfaces (130 nm grooves separated by 130 nm) of various depths (100, 210 and 400 nm) was examined. While all gratings aligned BHK cell populations, the degree of alignment was dependent on depth. The response of single MDCK cells to the grating patterns was both to align precisely to the direction of the gratings, and to elongate; only their elongation was depth-dependent. MDCK cells that were part of epithelial cell islands, and the outgrowth of neurites from chick embryo neurones, were mainly unaffected by the grating surfaces. It is clear that topography on this scale can control cell behaviour, but guidance of this type is strongly dependent on cell type and cell cell interactions. PMID- 1757504 TI - Rapid and transient reorganization of the cytoskeleton in GH3B6 cells during short-term exposure to thyroliberin. AB - The cytoskeletal organization of the rat pituitary tumor cell line GH3B6 was analysed using immunofluorescence, in basal conditions and after stimulation by thyroliberin (TRH). Under basal conditions, a dense and entangled cytoplasmic microtubule network, a perinuclear cage of cytokeratin fibers, and a diffuse distribution of F-actin were revealed. Short-term stimulation of these cells by TRH induces a first early phase of PRL release (0-2 min), concomitant with a rarefaction of cytoplasmic PRL-containing granules, followed by a second plateau phase (5-30 min), concomitant with modifications of the Golgi zone. We show that TRH induced early and transient modifications in the cytoskeletal distribution during these short periods of stimulation. First, after 2 min of stimulation, small fluorescent tubulin blebs appeared under the plasma membrane. Then, after 5 min they disappeared, and a thin actin network, accentuated by thicker fibers, organized transiently in the cytoplasm. After 30 min, the microtubules and cytokeratin networks had extended throughout the cytoplasm and the actin distribution was diffuse again. So, in this study, we have shown the existence of a parallelism between the redistribution of intracellular PRL compartments and the reorganization of cytoskeletal elements, during exposure to TRH. We could not clearly correlate these modifications with transduction mechanisms involved in TRH action. PMID- 1757505 TI - Ultrastructure of chromatin. I. Negative staining of isolated fibers. AB - The ultrastructure of chromatin fibers isolated from erythrocyte nuclei of Necturus maculosus and contrasted with a number of negative stains is described. Long (greater than 1000 nm) fibers are prepared under ionic conditions that promote fiber integrity, fixed with glutaraldehyde and negatively stained with aurothioglucose, ammonium molybdate, methylamine tungstate, sodium phosphotungstate, uranyl acetate and a uranyl acetate-sodium phosphotungstate sequence. All stains yield images of '30 nm' chromatin fibers, but aurothioglucose gives the most consistent diameter measurements (33 nm, S.D. 3.5 nm), and provides the clearest images of individual nucleosomes. Regions of fiber showing structural order are seen with all stains. The most commonly observed is a regular pattern of oblique cross-striations consistent with the visualization of the 'top' or 'bottom' of a helical structure. There is a significant relationship between fiber diameter and the cross-striation angle, consistent with an extensible chromatin fiber. Examination of power spectra prepared from selected ordered regions confirms the visual impressions, and indicates a striation spacing ranging from 11 nm to 18 nm, and dependent on the stain type. Fibers allowed to unfold slightly in a buffer containing 50 mM monovalent ions show evidence of a two-stranded helix-like organization. These results are discussed in terms of current models for the structure of the chromatin fiber. PMID- 1757506 TI - CASPER: a computer program used for structural analysis of carbohydrates. AB - The computer program CASPER and its algorithms are described. The program is aimed at facilitating the determination of structures of oligosaccharides and regular polysaccharides, requiring as input either the one-dimensional 1H or 13C NMR spectrum or the 2D C,H-correlation NMR spectrum together with information on components and linkages. The databases, the method of simulating spectra, options of the program, and techniques for faster calculations are described as well as an example of a structural determination. PMID- 1757507 TI - A method for automatic generation of novel chemical structures and its potential applications to drug discovery. AB - A novel method for generation of chemical structures of potential pharmaceutical interest is presented. Structures are generated by random combination of known fragments and selected by statistical topological techniques. The power of the method lies in the great profusion of candidates generated together with the extremely high selectivity imposed by the techniques of selection. PMID- 1757508 TI - The emperor's new clothes. PMID- 1757509 TI - Inhibin and gonadotrophin secretion in physically active males after acute exercise. AB - Serum concentrations of luteinizing hormone (LH) follicle stimulating hormone (FSH), testosterone and inhibin were measured in six physically active male volunteers after heavy exercise on a treadmill. Hormone measurements were made before exercise, immediately after exercise and at 30-min intervals for 3 h after exercise. Serum concentrations of LH fell after exercise reaching nadir values between 60 and 180 min post-exercise. The nadir value of LH for the group as a whole occurred 90 min after exercise. Serum testosterone concentrations paralleled the changes in LH concentrations. Serum FSH and inhibin concentrations did not show any appreciable change from baseline values. The data suggest that acute exercise does not significantly lower serum concentrations of FSH or inhibin. Whether repetitive and prolonged heavy exercise, as in competitive runners, produces alterations in serum inhibin concentrations remains to be determined. PMID- 1757510 TI - Effects of stage of the bovine oestrous cycle on in-vitro characteristics of uterine and oviductal epithelial cells. AB - The objective of this experiment was to evaluate the effects of stage of the bovine oestrous cycle on in-vitro morphology, growth and monolayer foundation of uterine and oviductal epithelial cells. Epithelial cells were isolated from the uterus and oviducts collected from cyclic cattle on the day of oestrus (Treatment A), and between days 4 to 6 (Treatment B), days 8 to 10 (Treatment C) and days 14 to 16 (Treatment D) of the oestrous cycle. The morphological development, per cent cell viability and cell attachment were evaluated during primary culture and after the first and third subpassages. The highest per cent cell viability and cell attachment during primary culture, respectively, were noted in Treatment B for both uterine (87.7 and 87.5%) and oviductal (88.4 and 87.2%) cell populations. Uterine epithelial cell populations in Treatments C and D, respectively, had the lowest viability (76.5 and 68.8%) and attachment (10.8 and 10.5%) during primary culture. There were marked improvements in cell viability and cell attachment following the first subpassage (P less than 0.001) compared with primary cultures for both uterine and oviductal cells. These results indicate that the stage of the oestrous cycle has dramatic effects on uterine and oviductal epithelial cell morphology and developmental patterns during primary in vitro cultures. The stage of the oestrous cycle when cells are collected may be more important than was once realized when culturing early stage embryos in vitro. PMID- 1757511 TI - The role of measurement of progestagen-associated endometrial protein in predicting adequate endometrial differentiation. AB - Late secretory endometrium synthesizes and secretes progestagen-associated endometrial protein (PEP), which is measurable in the serum of cycling women, and has been shown to increase in concentration during the luteal phase of the normal menstrual cycle. The purpose of this study was to determine the utility of serum PEP as a predictor of normal or inadequate luteal phase endometrial differentiation. One-hundred-and-twenty-five endometrial biopsies were taken within 4 days of a subsequent menstrual period, during the course of evaluation of infertility or recurrent abortion. Twenty-one of these biopsies demonstrated glandular/stromal asynchrony. Thirteen patients exhibited 'out-of-phase' endometrial biopsies and 91 patients had 'in-phase' biopsies. Mean PEP values significantly increased from the mid-luteal phase to the late luteal phase. Mean PEP values for patients with in-phase biopsies (43.92 units/ml) were not significantly different from those with out-of-phase biopsies (25.24 units/ml, P = 0.0942). PEP values for patients with asynchronous biopsies were intermediate. Use of clomiphene citrate did not affect these results. PMID- 1757512 TI - Stress-related hormones affect human chorionic gonadotrophin secretion from the early human placenta in vitro. AB - The effect of a physiological range of concentrations of three stress-related hormones, oxytocin (OT), arginine-vasopressin (AVP) and prolactin (PRL) was tested upon human chorionic gonadotrophin (HCG) secretion by placental explants from early pregnancy in static and superfusion cultures. In static cultures, OT and AVP significantly increased HCG secretion, whereas PRL had no effect. In superfusion, 1-min pulses of OT induced a significant (two- to 10-fold) rise in HCG pulse amplitude compared to the control. This effect of this neuropeptide was blocked by coadministration of a specific receptor antagonist. AVP also increased the glycoprotein pulse amplitude by two- to five-fold, but only with every second pulse administered. PRL pulses caused a progressive inhibition of spontaneous HCG pulsatility. In conclusion, stress-related hormones affect placental HCG secretion in vitro. The involvement of these factors in impairing early pregnancy development is suggested. PMID- 1757513 TI - The effect of oxytocin on oestradiol-17 beta and testosterone secretion by cultured human granulosa cells. AB - The effect of oxytocin at different concentrations was tested on the secretion of oestradiol-17 beta and testosterone by cultured human granulosa cells obtained by follicular punctures during in-vitro fertilization (IVF) attempts. Oxytocin had no effect on testosterone secretion, either in the absence or the presence of follicle stimulating hormone (FSH). It had no effect on oestradiol-17 beta in the absence of FSH. However, it decreased the FSH-stimulated secretion of oestradiol 17 beta in a certain number of cases. This inhibitory effect appears to be associated with cells more responsive to FSH and was identified in women found to be successful in achieving pregnancy during IVF attempts. PMID- 1757514 TI - Preincubation of human granulosa cells with gonadotrophin prevents the cloprostenol-induced inhibition of progesterone production. AB - Human granulosa cells, from women undergoing ovum collection for in-vitro fertilization (IVF), will luteinize in vitro and provide a model for investigating the antigonadotrophic action of a prostaglandin F2 alpha (PGF2 alpha) analogue, cloprostenol, on granulosa-derived luteal cells. The granulosa cells were cultured in a defined medium and exposed to treatments during a preincubation period of 0 to 3 days and a final incubation with low density lipoprotein (LDL) from days 3 to 4. In the absence of human chorionic gonadotrophin (HCG), progesterone production was low, whereas exposure to HCG in the final incubation resulted in a 10-fold increase in progesterone concentrations. The inclusion of cloprostenol with HCG in the final incubation significantly (P less than 0.05) inhibited HCG-stimulated progesterone production. Exposure to HCG during the preincubation prevented the antigonadotrophic action of cloprostenol in the final incubation. The antigonadotrophic action of cloprostenol was retained when the granulosa cells were exposed to cloprostenol during the preincubation. Omission of LDL from the final incubation lowered the production of progesterone but the pattern of responses to HCG and cloprostenol were similar. Prevention of the antigonadotrophic action of cloprostenol after exposure to HCG may be a mechanism through which chorionic gonadotrophin can prevent regression of the corpus luteum in early pregnancy. Cloprostenol does not appear to inhibit LDL-stimulated steroidogenesis in human granulosa cells. PMID- 1757515 TI - Effect of clomiphene citrate on the synthesis and release of the human beta lactoglobulin homologue, pregnancy associated endometrial alpha 2-globulin, by the uterine endometrium. AB - As an extension to a previous study to examine the effects of clomiphene citrate (CC) on human chorionic gonadotrophin/luteinizing hormone (LH) receptors in human corpora lutea, we sought to determine the effect of CC on the synthesis of the beta-lactoglobulin homologue, pregnancy associated endometrial alpha 2-globulin (alpha 2-PEG) by the luteal phase human endometrium. Seventeen normally-cycling women aged 25.9 +/- 2.1 years (mean +/- SE), undergoing elective tubal ligation, were divided into four groups consisting of controls (n = 2) and three treatment groups. Each of the treatment groups (n = 5/group) was treated with either 50 mg (group 1), 100 mg (group 2) or 150 mg (group 3) of CC daily on days 5 to 9 of the cycle. Portions of endometrial tissue were obtained by curettage 7 to 9 days following the urinary LH surge and were either fixed for histological analyses or cultured in vitro in the presence of [35S]methionine. Tissue media (TCM) that were analysed by two-dimensional gel electrophoresis followed by fluorography indicated that the synthesis of alpha 2-PEG was most markedly reduced in groups 2 and 3. Densitometric scans of TCM Western blots and radioimmunoassay (RIA) of TCM showed that the overall synthesis of alpha 2-PEG decreased from 5.8 +/- 1.9 arbitrary units (AU) and 371.2 +/- 239.3 ng/ml in group 1 to 3.1 +/- 0.8 AU and 69.4 +/- 24.9 ng/ml, and 2.7 +/- 1.1 AU and 52.4 +/- 19.8 ng/ml in groups 2 and 3 respectively. On cycle days 20-22, control values were 5.8 AU and 498.1 ng/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757516 TI - Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. AB - Granulated lymphocytes with an unusual antigenic phenotype (CD56+ CD38+ CD2 +/- CD3- CD16-) form a substantial proportion of leukocytes in human endometrial stroma. The purpose of this study was to examine morphological and antigenic heterogeneity in endometrial granulated lymphocytes (eGL) in imprint preparations, paraffin-embedded sections and frozen sections. eGL in decidual imprints showed variations in cell size, nuclear size, shape and chromatin content and the number and size of cytoplasmic granules. eGL were detected in paraffin-embedded sections using phloxine tartrazine, alcian blue and toluidine blue stains. There was no difference in the number of eGL among the three stains but the granules appeared smaller and more regular when stained with toluidine blue. The proportion of stromal cells which were leukocytes increased from 8.2% in proliferative endometrium to 31.7% in early pregnancy decidua. The number of CD56+ and CD38+ cells increased in late secretory endometrium; CD56+ cells formed greater than 75% of the leukocytes in first trimester decidua. The increased number of CD2+ cells in decidua was not comparable with CD56+ and CD38+ cells suggesting that a lower proportion of CD56+ cells in first trimester decidua coexpress CD2, an observation which was supported by double labelling studies. eGL therefore show morphological and antigenic heterogeneity and the study of granulated lymphocytes in pathological endometrium and decidua will require careful phenotypic and morphological analysis of accurately dated samples. PMID- 1757517 TI - Pregnancy rates after transfer of embryos obtained from different stimulation protocols and frozen at either pronucleate or multicellular stages. AB - After in-vitro fertilization, 2161 supernumerary embryos were frozen with 1,2 propanediol and sucrose as cryoprotectants at either pronucleate or multicellular (2-6 blastomeres) stages. By the end of March 1990, 494 pronucleate stage embryos and 492 multicellular stage embryos had been thawed and 54 and 47% of them, respectively were considered suitable for transfer. Ongoing pregnancy and implantation rates were 17.9 and 10.7%, respectively for embryos frozen at the pronucleate stage and 5.5 and 4.7% for embryos frozen at the multicellular stage. Ovarian stimulation with human menopausal gonadotrophin (HMG) after pharmacological hypophysectomy with a gonadotrophin releasing hormone agonistic analogue (GnRHa) using a long protocol permitted us to freeze significantly more embryos per cycle (7.2 +/- 4.1) than stimulation with HMG and GnRHa in a short protocol (4.7 +/- 3.4) or stimulation with clomiphene citrate (CC) and HMG (2.7 +/- 1.9). Ongoing pregnancy rates after transfer during the stimulated cycles were similar for the three types of treatment (27.1, 27.3 and 32.1%, respectively). However, ongoing pregnancy rates after frozen-thawed embryo transfers were significantly higher when originating from GnRHa + HMG treatments (14.3 and 14.8%, respectively for long and short protocols) than when originating from CC + HMG treatment (5.6%). Embryo cryopreservation has permitted the ongoing pregnancy rate to increase from 28.4 to 36.9% (P less than 0.01) even though more than half of the embryos have not been thawed. We conclude that embryos obtained after stimulation with GnRHa + HMG and frozen at the pronucleate stage are more likely to result in a pregnancy. PMID- 1757518 TI - Results of IVF from a prospective multicentre study. AB - Part of a cost-effectiveness study of in-vitro fertilization was the evaluation of the medical results of this fertility treatment. Data were prospectively collected from greater than 3000 IVF treatments in five Dutch hospitals during a 2-year period. The average 'take-at-least-one-healthy-baby-home-rate' per started treatment was 10% (the average clinical pregnancy rate per embryo transfer was 20%). After more IVF treatments, about one in three to four couples were successful. Differences in results were mainly caused by patient characteristics, the treatment episode and the treating hospital. These differences remained in a multivariate logistic regression analysis. PMID- 1757519 TI - Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). AB - To estimate the prevalence and main causes of infertility, a multicentre survey was conducted over 1 year (July 1988-June 1989) in three regions of France. All the 1686 couples in these regions, who consulted a practitioner for primary or secondary infertility during this period, were included in the investigation. The prevalence rate of infertility was found to be 14.1%, indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life. The main causes of female infertility were ovulation disorders (32%) and tubal damage (26%), and of male infertility oligo-terato asthenozoospermia (21%), asthenozoospermia (17%), teratozoospermia (10%) and azoospermia (9%). Infertility was also found to be caused by disorders in both the male and female partners together; thus in 39% of cases both the man and woman presented with disorders. The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth. Unexplained infertility was found in 8% of the couples surveyed. PMID- 1757520 TI - The leuprolide flare regime for in-vitro fertilization/gamete intra-fallopian transfer and embryo cryopreservation. AB - Gonadotrophin releasing hormone agonists (GnRHa) are now well established as adjuvant agents for in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) but several different modes of usage have been proposed. Our experience with 328 cycles of leuprolide used in a flare regime is reviewed. An endocrinologically proven flare effect was associated with a reduction of human menopausal gonadotrophin (HMG) usage (10 versus 16 ampoules) and a lower cycle cancellation/conversion rate (7.4 versus 11.3%). Overall, satisfactory rates of oocyte recovery (93%, mean number of oocytes 7.0), clinical pregnancy (24.4% per oocyte recovery) and pregnancy from frozen/thawed embryo transfers (14%) were achieved. The flare protocol appears to be a satisfactory choice for the majority of subjects but careful monitoring is required to avoid the potential for ovarian hyperstimulation. PMID- 1757521 TI - Contribution of preovulatory-phase small follicles to the ovarian response in stimulated cycles. AB - The usual criteria for ovulation induction in stimulated cycles take into account the number of follicles greater than 14-16 mm in diameter. We have retrospectively investigated how the presence of small (8-12 mm) follicles at the time of the last scan influences the ovarian response for in-vitro fertilization (IVF). The mean number of small follicles was nearly constant (3.8 to 5.9) and did not correlate with the number of large (greater than 12 mm) follicles in various protocols for ovarian stimulation. In patients stimulated under the influence of a gonadotrophin releasing hormone (GnRH) agonist, the number of small follicles was correlated with the oestradiol (E2) peak level and with the number of recovered oocytes. Our data demonstrate a significant contribution of follicles less than or equal to 12 mm to peripheral E2 levels and oocyte production for IVF. PMID- 1757522 TI - Salpingitis isthmica nodosa in female infertility and tubal diseases. AB - Salpingitis isthmica nodosa (SIN) is a condition of nodular thickening of the proximal Fallopian tube. The purpose of this study was to investigate the occurrence, distribution and frequency of SIN in Danish women salpingectomized because of tubal pregnancy or salpingitis and to correlate SIN with infertility, pregnancies, outcome of pregnancies, births, pelvic inflammatory disease and salpingitis. Sections from the isthmus were present in the specimens from 223 tubes from 193 patients and were analysed by the same pathologist. Originally, SIN was found in 12 patients but on re-examination, it was found in 24 patients. Ten women with SIN were bilaterally salpingectomized. Only one woman had SIN in both tubes. Women with SIN gave birth to as many children as women without SIN. After SIN had been diagnosed, no children were born, but this was not statistically different from the frequency of births in the non-SIN group after salpingectomy. Women with SIN had histological signs of salpingitis more often than women without SIN, but SIN complicated with salpingitis did not influence the number of children or tubal pregnancies. Women with SIN had a greater risk of two or more tubal pregnancies than women without SIN. PMID- 1757523 TI - The effects of cryopreservation and thawing on the development in vitro and in vivo of biopsied 8-cell mouse embryos. AB - The possible impact of cryopreservation on biopsied 8-cell mouse embryos was investigated. Biopsied and control 8-cell embryos were cryopreserved using a slow freezing and quick thawing protocol with 1,2-propanediol as a cryoprotectant. The cryopreservation process did not affect either the recovery or the survival of biopsied embryos, when compared with intact controls; however, sham controls survived significantly better than biopsied 8-cell embryos (88.6 versus 74.2%, P less than 0.001). When fully and partially intact surviving embryos were cultured in vitro to the blastocyst stage, there was no difference in the proportions of embryos which formed blastocysts (biopsy 97.2%, intact control 98.4% and sham control 93.7%). The developmental potential and fetal development in vivo following embryo transfer were not impaired when assessed on day 17 of pregnancy. Cryopreservation of biopsied 8-cell mouse embryos is therefore a feasible approach to storing embryos while analysis of the biopsied material is carried out. PMID- 1757524 TI - Using PCR in preimplantation genetic disease diagnosis. AB - Preimplantation diagnosis of genetic disease can be accomplished by embryo biopsy or polar body analysis using in-vitro gene amplification (PCR). PCR analysis of single cells is subject to a number of errors which decrease the reliability of the diagnosis. Using realistic assumptions about error rates based on experimental data, we analyse some of the practical consequences to be faced by whose wishing to use this diagnostic procedure. We considered both autosomal dominant and recessive diseases. We calculate the probability of making mistakes in the diagnosis, assuming a realistic range in the magnitude of PCR efficiency, cell transfer, and contamination errors. We conclude that, in general, analysing blastomeres is subject to less mis-diagnosis than polar body analysis, except in the case of dominant diseases which are caused by genes which lie extremely close to the centromere. We also show that typing multiple blastomeres from a single embryo or combining polar body typing with blastomere analysis results in significantly lower levels of mis-diagnosis with unacceptable consequences. The preimplantation diagnosis of X-linked diseases based upon Y chromosome sequence analysis is also discussed. PMID- 1757525 TI - Epididymal secretory function in men with asthenoteratozoospermia. AB - Epididymal function was evaluated in normozoospermic men and men with asthenoteratozoospermia using alpha-glucosidase as a secretory parameter. No difference was observed in the total quantity of the enzyme secreted into the ejaculate in spite of major differences between the two groups in the proportion of spermatozoa exhibiting progressive motility and normal morphology. In general, the secretion of alpha-glucosidase was positively correlated with the sperm concentration in the normozoospermic group, but not in asthenozoospermic subjects. The total enzyme contents of the ejaculate were significantly greater in men with asthenoteratozoospermia (sperm concentrations, greater than 35 x 10(6)/ml) than in subjects with severe oligoasthenoteratozoospermia (sperm concentrations less than 10 x 10(6)/ml, P less than 0.01) indicating a higher incidence of epididymal occlusion and/or dysfunction in the latter group. Within normozoospermic individuals, extremes in progressive motility or abnormal morphology could not be related to the quantities of enzyme when expressed per million sperm cells. It is concluded that if alpha-glucosidase is a reliable parameter of human epididymal secretory function, variation in the secretory function of the epididymis cannot explain the poor sperm quality observed in asthenoteratozoospermic individuals. PMID- 1757526 TI - Variations in semen parameters from fathers. AB - Semen volume, pH, sperm characteristics and the ejaculate content of six compounds secreted by the epididymides, prostate and seminal vesicles are presented for several semen samples from 25 men (mean age 31 years) who, without clinical assistance, had fathered children within the previous 29 months. There was a large variation both within and between individual's samples for concentrations and amounts per ejaculate of all parameters except pH. The range including 96% of all values from these fertile men are presented as standards against which samples from infertile men could be compared. Lower limits (combined arithmetic means minus twice the combined within- and between-father standard deviation) were: for semen volume, 1.9 ml; for semen pH, 7.4; for total sperm count, 39 X 10(6); for normal morphological forms, 42%; for motility (WHO grades) a, 4%; b, 19%; c, 1%; d, 19%; for curvilinear velocity, 27 microns/s; for total glucosidase, 27 mU/ejaculate; for neutral alpha-glucosidase, 17 mU/ejaculate; for L-carnitine, 0.4 mumol/ejaculate; for glycerophosphocholine, 2.4 mumol/ejaculate; for fructose, 15 mumol/ejaculate; for citrate, 30 mumol/ejaculate; for zinc, 2.8 mumol/ejaculate. PMID- 1757527 TI - Free radical scavengers ameliorate the 2-cell block in mouse embryo culture. AB - Mouse zygotes from a strain combination which fails to undergo cleavage in vitro (the 2-cell block) were cultured in a variety of media, using either low (5%) or normal (20%) oxygen tension in the gas phase. Development beyond the 4-cell stage was only achieved in medium containing serum and with normal oxygen tension. When serum-free medium was supplemented with free radical scavengers, reduced glutathione (1 mM), but not histidine, catalase or superoxide dismutase, development to the morula or blastocyst stage was promoted in 50% of zygotes cultured with normal oxygen tension. These data suggest that the 2-cell block is a consequence, at least in part, of free radical damage incurred by embryos during collection and culture, and that medium supplementation with the radical scavenger, reduced glutathione, can improve embryo development in vitro. PMID- 1757528 TI - Comparison of a radioimmunoassay and bioassay for embryo-derived platelet activating factor. AB - The pre-embryos of a number of species produce platelet-activating factor (PAF). This study compared the sensitivity, reproducibility and cross-reactivity of a radioimmunoassay (RIA) for PAF with a quantitative PAF bioassay and assessed the use of both assays for the measurement of murine and human embryo-derived PAF. PAF was extracted and partially purified by thin-layer chromatography (TLC) from medium in which mouse (30 x 2-cell) or individual human embryos [produced by in vitro fertilization (IVF)] had been cultured for 24 h. Dose-response curves were generated with synthetic PAF standards over a concentration range of 0.3-30 ng/ml. The RIA was slightly more sensitive than the bioassay since the concentration which gave 50% response in the RIA was 3 ng/ml compared to 6 ng/ml in the bioassay. The RIA showed greater reproducibility than the bioassay, since at these concentrations the coefficients of variation were 1.97 and 6.77% intra assay and 4.96 and 10.93% inter-assay, respectively. Both assays had a detection limit of 0.3 ng/ml. C-PAF, a non-metabolizable bioactive analogue of PAF, showed 5.16 and 0.85% cross-reactivity in the bioassay and RIA, respectively, while lyso PAF and phosphatidylcholine had no effect. Following extraction and TLC, the average PAF concentration was 14.52 ng/ml (range 0.10-141.09) and 20.06 ng/ml (range 0.07-106.15) for mouse embryos, and 16.15 ng/ml (range 0.40-78.31) and 23.70 ng/ml (range 2.00-119.10) for human embryos, as measured by bioassay and RIA respectively. Therefore, both the bioassay and RIA were capable of the sensitive quantitative measurement of embryo-derived PAF. PMID- 1757529 TI - Fertilization and ageing processes in non-divided human oocytes after GnRHa treatment: an analysis of individual oocytes. AB - Some human oocytes cultured together with spermatozoa for in-vitro fertilization (IVF) do not subsequently divide. The arrest of the fertilization process at different moments during development may provide information about the cause of fertilization failure. Oocytes which subsequently divide are transferred 48 h after insemination; when oocytes do not divide, ageing processes can be observed. Therefore these oocytes are interesting material in which to observe both fertilization and ageing. Our study concerns 72 undivided human oocytes 0, 48 or 72 h post-insemination. DNA of the oocyte and spermatozoa was visualized by the DNA fluorescent dye Hoechst 33342. Living oocytes were observed in toto by fluorescence and bright field microscopy which allowed nuclear and pronuclear membranes to be discerned. Oocytes were subsequently fixed and sectioned for bright field microscopy. Both techniques allowed parallel observations. Oocytes at various stages of fertilization are described: sperm penetration in both mature and immature oocytes, decondensation of sperm-heads, premature condensation of male chromatin, polyspermy and pronucleus formation. Typical ageing processes such as the centripetal migration of the metaphase II chromosomes, the formation of a restitution nucleus and the lagging of chromosomes within a metaphase spindle are observed. DNA fluorescence appears to be a quick, easy and valuable means to analyse fertilization and its failure. PMID- 1757530 TI - Secretory endometrial protein PP14 in women with early pregnancy bleeding. AB - The decidualized endometrium produces secretory proteins of which secretory endometrial protein PP14 is the major product during the first trimester of pregnancy. The protein is secreted into the uterine lumen as well as into the peripheral blood. The purpose of this study was to examine whether decidual function, evaluated by the serum concentration of PP14, was different in women with early pregnancy bleeding compared to normal pregnant women. A reference range for serum PP14 was established on the basis of single samples from 236 normal pregnant women with ultrasonically confirmed gestational age. All the women were delivered of a normal child at term. The study comprised 128 pregnant women admitted because of vaginal bleeding between 6 and 18 weeks gestation. At ultrasonography, intrauterine fetal heart activity was either present or was confirmed at a subsequent examination. No difference was found in the serum level of PP14 compared to that in normal pregnancies, but women with vaginal bleeding and depressed PP14 levels appeared to have a 5-fold higher risk of preterm delivery than women with bleeding and normal PP14 levels. PMID- 1757531 TI - Anti-phospholipid antibodies and pregnancy loss. AB - Anti-phospholipid antibodies such as the lupus anticoagulant and anti-cardiolipin antibodies, are antibodies directed at negatively charged phospholipids and have received much attention in the last decade. Their presence has been associated with a thrombotic tendency, leading to a variety of clinical symptoms. In the pregnant woman, the presence of these antibodies may have consequences for management, since retrospective reports have established a correlation between the lupus anticoagulant or anti-cardiolipin antibodies with intrauterine fetal death, probably due to placental thrombosis. This article reviews current knowledge on anti-phospholipid antibodies in relation to pregnancy loss, focusing on clinical aspects. PMID- 1757532 TI - Maternal death associated with ovum donation twin pregnancy. AB - A case of maternal death due to sub-arachnoid haemorrhage in an ovum donation twin pregnancy complicated by hypertension is described. Attention is drawn to a forecasted increase in maternal morbidity and mortality in in-vitro fertilization (IVF) pregnancies, which occur in older women and are often multiple. PMID- 1757533 TI - Performance of a nonisotopic DNA probe for detection of Chlamydia trachomatis in urogenital specimens. AB - The Gen-Probe PACE 2 assay (GP), a nonisotopic DNA probe, was evaluated by using cell culture as the method of reference. Specimens were collected from 260 men and 482 women visiting the outpatient department for sexually transmitted diseases at the University Hospital in Rotterdam, The Netherlands. The prevalences of Chlamydia culture-positive men and women were 13.2 and 8.6%, respectively. Sensitivity values for the male and female patients were 70.6 and 92.7%, respectively. Specificity values for these groups were 98.2 and 97.7%, respectively. Sensitivity was significantly lower when the number of inclusions in cell culture was low. Samples which showed a discordance between cell culture and GP results were retested by the polymerase chain reaction. If the results of the polymerase chain reaction were considered as the points of reference, the sensitivity and specificity of both GP and cell culture could be calculated. The performance of GP for females was comparable to that of cell culture. In males, the sensitivity of GP was considerably lower than that of cell culture (77.2 versus 91.4%), while specificity was somewhat higher (99.6 versus 99.1%). Compared with cell culture, the GP is a relatively simple and rapid test that is suitable for diagnosing Chlamydia infections in urogenital specimens. PMID- 1757534 TI - Genomic DNA fingerprinting by pulsed-field gel electrophoresis as an epidemiological marker for study of nosocomial infections caused by methicillin resistant Staphylococcus aureus. AB - In this study, we have compared genomic DNA fingerprintings among isolates of methicillin-resistant Staphylococcus aureus (MRSA) by using pulsed-field gel electrophoresis (PFGE). Chromosomal fragments digested with SmaI were most suitable for the PFGE separation. SmaI cut genomic DNA into 15 to 20 fragments whose sizes ranged from about 30 to 1,500 kb. Thirty-one distinctive fragment patterns were identified in 111 infecting and colonizing MRSA isolates from six different hospitals in Japan. On the basis of the genomic typing by PFGE, we performed an epidemiological investigation of an outbreak of nosocomial MRSA infections among inpatients in Nagoya University Hospital. Ten types of chromosomal digestion were identified in the 20 strains isolated from 18 infected patients and 1 from colonized hospital personnel. According to the restriction patterns, we found that four types of these strains had caused epidemic infections among 13 patients in the outbreak. Two types (types 1 and 4) of the strains were involved in the death of five patients. The other infections were sporadic. The clarity and polymorphism of the chromosomal digestion patterns enabled us to discriminate between isolates which could not be differentiated by antibiogram or plasmid analysis. Classification of the genomic DNA fingerprinting patterns by PFGE is therefore proposed as a useful method for investigating the source, transmission, and spread of nosocomial MRSA infections. PMID- 1757535 TI - Rhodococcus equi plasmids: isolation and partial characterization. AB - Fifty-four strains of Rhodococcus equi from different clinical sources (mainly horses and pigs) were examined for their plasmid content by two screening methods. Plasmids were detected in 49 of 54 strains. A plasmid of approximately 80 kb was isolated from 21 of 22 isolates from horses and 20 of 28 isolates from pigs, and a 105-kb plasmid was isolated from 7 of 28 isolates from pigs. The 80 kb plasmid was significantly associated with strains of equine rather than porcine origin, and the 105-kb plasmid was significantly associated with strains of porcine origin. The type strain, ATCC 6939, consistently failed to yield a plasmid. Restriction enzyme analysis of purified plasmid DNA confirmed the relatedness of the 80-kb plasmids isolated from strains of equine and porcine origin. More differences between the restriction patterns of plasmids from strains isolated from horses and from pigs than among strains from either species were observed. Restriction enzyme analysis also showed relatedness of the 105-kb plasmid to the 80-kb plasmid. Three strains shown by others to be virulent in horses or mice possessed the 80-kb plasmid, whereas three other strains not virulent for horses or mice lacked the plasmid, although one had the 105-kb plasmid. There was a significant but not perfect association between the presence of the 80-kb plasmid and production of a diffuse 17.5-kDa thermoregulated, virulence-associated protein. Further study is needed to determine whether this plasmid is associated with virulence in R. equi. PMID- 1757536 TI - Development of verotoxin 2- and verotoxin 2 variant (VT2v)-specific oligonucleotide probes on the basis of the nucleotide sequence of the B cistron of VT2v from Escherichia coli E32511 and B2F1. AB - We and others have noted that there are serological differences between verotoxin 2 (VT2) (also known as Shiga-like toxin II) produced by Escherichia coli C600(933W) and the VT2 variant (VT2v) produced by strain E32511. Recent reports have described nucleotide sequence differences between the VT2v B subunit cistron of E32511 and B2F1 and that of VT2. We have confirmed the sequence differences and have used them to design oligonucleotide probes which differentiate the B subunit cistron of VT2v from that of VT2. Isolates of VT-producing E. coli obtained from human as well as food and veterinary sources were classified according to the toxin phenotype by using a toxin neutralization assay with VT2 specific monoclonal antibody and VT2v-specific polyclonal antisera. Using the oligonucleotide probes in colony hybridization, we detected 35 of 35 VT2 producers and 16 of 16 VT2v producers. One VT2 producer was falsely identified as containing the VT2v gene. The E32511 strain in our collection hybridized only with the VT2-specific probe. Southern hybridization of radiolabeled oligonucleotide probes showed that strains carried zero to one copy of the VT2 gene and zero to two copies of the VT2v gene. We conclude that colony hybridization with the VT2- and VT2-specific probes is highly predictive of the toxin phenotypes in the clinical isolates described in this study. PMID- 1757537 TI - Immunoglobulin binding by Tritrichomonas foetus. AB - A better method for diagnosis of bovine trichomoniasis is needed because culture is slow and somewhat lacking in sensitivity. Immunodiagnosis of Tritrichomonas foetus infection usually involves detection of antigen-antibody reactions with an anti-immunoglobulin conjugate. However, nonspecific immunoglobulin (Ig), bound to the surface of T. foetus, would also be detected by an anti-Ig conjugate and thus would interfere with the specificity of the immunoassay. The goals of this study were to define the binding of bovine immunoglobulins to T. foetus. To determine whether nonimmune binding of Ig to T. foetus occurs, we immunized rabbits with organisms that had been grown in medium containing normal bovine serum and vigorously washed three times with phosphate-buffered saline. The rabbit antiserum had similar titers to T. foetus and to normal bovine serum by enzyme linked immunosorbent assay (ELISA). Furthermore, two bovine serum proteins were immunoprecipitated by the rabbit antiserum in an immunoelectrophoretogram. One of the serum proteins had a distribution characteristic of IgG2. The rabbit antiserum was then shown to react with purified bovine IgG and IgM by ELISA. Reactivity to IgG was greater. To identify the IgG subisotypes bound and to confirm nonimmune binding of Ig, we grew T. foetus in agammaglobulinemic fetal calf serum and reacted it with IgG1, IgG2, and IgM specific for dinitrophenol (DNP) in ELISA. The binding of IgG2 was greatest, that of IgG1 was next, and that of IgM was least. Little competitive inhibition by DNP was detected, indicating that binding of DNP-specific antibodies was predominantly nonimmune rather than antigen-specific Ig binding. We also demonstrated that T. foetus grew well in medium containing agammaglobulinemic fetal calf serum or serum made agammaglobulinemic by ammonium sulfate precipitation of Igs. This may overcome the problem of low specificity in diagnostic assays as a result of antigen with Ig bound by nonimmune mechanisms. PMID- 1757538 TI - Mycobacterium avium complex disease in patients with AIDS: seroreactivity to native and recombinant mycobacterial antigens. AB - Antibodies to Mycobacterium avium complex (MAC) antigens were measured by enzyme linked immunosorbent assays and immunoblot analyses in sera from 20 patients with AIDS and disseminated MAC disease, 5 human immunodeficiency virus-seronegative patients with pulmonary MAC infections, and 20 healthy controls. Whereas enzyme linked immunosorbent assay titers for healthy controls and patients with AIDS and MAC disease were comparable, human immunodeficiency virus-seronegative patients with MAC disease had higher anti-MAC antibody titers (P less than 0.01). Immunoblot analysis with the same sonic extracts indicated that each of the three groups had a limited heterogeneous response to M. avium antigens. No significant differences in immunoblot reactivities were detected. However, immunoblot studies with recombinant nontuberculous mycobacterial antigens revealed that sera from over 90% of the patients with MAC disease and only 25% of controls recognized a recombinant protein derived from a 35-kDa mycobacterial antigen. Although sonic extracts did not permit adequate discrimination of antibody reactivity in patients with MAC disease, recombinant antigens may be useful as indicators of disease. PMID- 1757539 TI - Group G streptococcal lymphadenitis in rats. AB - Group G streptococci which have been isolated from the oral flora of rats are also normal inhabitants of the human skin, oropharynx, gastrointestinal tract, and female genital tract. This group of streptococci can cause a wide variety of clinical diseases in humans, including septicemia, pharyngitis, endocarditis, pneumonia, and meningitis. Ten days after oral gavage with 7,12 dimethylbenz[a]anthracene, 12 of 22 two-month-old, female, outbred, viral antibody-free rats presented with red ocular and nasal discharges and marked swelling of the cervical region. Various degrees of firm, nonpitting edema in the region of the cervical lymph nodes and salivary glands as well as pale mucous membranes and dehydration were observed. Pure cultures of beta-hemolytic streptococci were obtained from the cervical lymph nodes of three rats that were necropsied. A rapid latex test system identified the isolates to have group G specific antigen. These streptococcal isolates fermented trehalose and lactose but not sorbitol and inulin and did not hydrolize sodium hippurate or bile esculin. A Voges-Proskauer test was negative for all six isolates. Serologic tests to detect the presence of immunoglobulin G antibody to rat viral pathogens and Mycoplasma pulmonis were negative. Histopathologic changes included acute necrotizing inflammation of the cervical lymph nodes with multiple large colonies of coccoid bacteria at the perimeter of the necrotiz zone. To our knowledge, this is the first report of naturally occurring disease attributed to group G streptococci in rats. PMID- 1757540 TI - Development of a rapid enzyme immunoassay for Clostridium difficile toxin A and its use in the diagnosis of C. difficile-associated disease. AB - A rapid (2.5 h) direct enzyme immunoassay (EIA) for Clostridium difficile toxin A was developed for clinical use. Specimen centrifugation and filtration were not required. The EIA detected toxin A levels in patient stool as low as 20 pg (2 ng/ml of stool). The test was 5,000 times more sensitive for toxin A than it was for toxin B and did not react with a panel of other bacterial species with the exception of one highly toxigenic strain of Clostridium sordellii. The EIA was compared with the cytotoxin assay, culture of toxigenic C. difficile (toxigenic culture), and latex agglutination by using 313 fresh stool specimens submitted from patients with suspected C. difficile-associated disease. Results read visually and with a plate reader were similar. Sixty-two specimens were positive by one or more tests, but only 22 (35%) were positive by all four laboratory methods. The EIA was 84.1% sensitive and 98.9% specific when it was compared with the cytotoxin assay. The use of toxigenic culture to referee discrepant results (EIA versus cytotoxin assay) showed the EIA sensitivity and specificity to be 95.1 and 99.3%, respectively, with respect to other laboratory methods. Patient charts were reviewed for antibiotic-associated diarrhea on 108 specimens, including all those that were positive by at least one test method. Of 34 patients determined to have C. difficile-associated disease, 29 (85.3%) were positive by EIA, 32 (94.1%) were positive by the cytotoxin assay, 27 (79.4%) were positive by toxigenic culture, and 20 (58.8%) were positive by latex agglutination. Seven patients with antibiotic-associated diarrhea had a positive latex result, but results were negative by EIA, the cytotoxin assay, and toxigenic culture. The EIA demonstrated high specificity and good sensitivity for C. difficile-associated disease cases. The test can be used alone or in combination with the cytotoxin assay or toxigenic culture to provide rapid and sensitive results. PMID- 1757541 TI - Differentiation of Lactococcus lactis and Lactococcus garvieae from humans by comparison of whole-cell protein patterns. AB - We tested 12 reference and 24 clinical strains of lactococci for physiologic characteristics using a conventional test system, the Gen-Probe Enterococcus 2 chemiluminescence assay (Gen-Probe Inc., San Diego, Calif.), the Rapid Strep identification system (Analytab Products, Plainview, N.Y.), and whole-cell protein analysis. The Gen-Probe Enterococcus 2 chemiluminescence assay for Enterococcus identification was negative with all strains. Neither the conventional test nor the Rapid Strep identification system could differentiate between the two Lactococcus spp. most commonly isolated from humans. A simple procedure, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was developed for comparing the whole-cell protein patterns of Lactococcus spp. L. lactis and L. garvieae were differentiated by unique protein patterns. PMID- 1757542 TI - Quantitative microculture system with standardized inocula for strain typing, susceptibility testing, and other physiologic measurements with Candida albicans and other yeasts. AB - A method for physiologic testing of Candida albicans and other yeasts is described in which inocula with reproducible cell concentrations are prepared from cultures in a glucose-limited medium and growth turbidities of test cultures in microplates are expressed quantitatively as a percentage of control growth. The method gave good within-plate and run-to-run reproducibilities and was applicable both to strain phenotype discrimination in C. albicans and to susceptibility tests of yeasts with azole antifungal agents. PMID- 1757543 TI - Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis. AB - A new disease was recognized in the United States in 1986. The etiologic agent, although not previously isolated from a human, appeared to be serologically related to Ehrlichia canis, a canine leukotropic rickettsia. We obtained blood specimens from 27 febrile patients with a history of tick exposure. Leukocytes from 24 patients not treated with tetracycline were placed onto a monolayer of DH82 cells. We performed indirect immunofluorescence on sera from all 27 febrile patients as well as sera from 12 patients with previously diagnosed ehrlichiosis. Intractoplasmic inclusions were first observed in culture 35 days after the addition of infected blood from one patient. Partial sequencing of the rRNAs from the human isolate and E. canis indicated that they are 98.7% related. Positive indirect immunofluorescence reactions to the human isolate were obtained for all 12 previously diagnosed patients and for 33% of the 27 febrile patients. Two patients were seropositive for the human isolate but not for E. canis. No sera were positive for E. canis and negative for the human isolate. We report the isolation of a previously unrecognized Ehrlichia sp. that appears to be the etiologic agent of human ehrlichiosis. Serologic data (range of antibody titers, 256 to 32,768) in combination with rRNA sequencing indicated that the newly isolated Ehrlichia sp. is similar, but not identical, to E. canis. PMID- 1757544 TI - Detection of variable DNA repeats in diverse eukaryotic microorganisms by a single set of polymerase chain reaction primers. AB - We cloned and sequenced a variable DNA repeat from Trichomonas vaginalis, a flagellated protozoan parasite. Targeting of this repeat in the polymerase chain reaction resulted in complex and intense product patterns for a wide variety of eukaryotic microorganisms, including the pathogenic protozoan parasites T. vaginalis, Giardia lamblia, Leishmania donovani, three species of Trypanosoma, and four species of Acanthamoeba; the nonpathogenic protozoans, Paramecium tetraurelia and Tetrahymena thermophilia; and a yeast, Saccharomyces cerevisiae. Each microorganism exhibited a distinctive pattern of repeats. For example, a characteristic pattern was exhibited by six clinical T. vaginalis isolates. Eight G. lamblia isolates exhibited either one of two characteristic pattern types. There was no reaction with human DNA or DNA from the prokaryotes Ureaplasma urealyticum and Mycoplasma hominis. This approach may facilitate detection of a wide variety of eukaryotic microorganisms by use of a single primer set and holds promise for the development of typing schemes for both T. vaginalis and G. lamblia. PMID- 1757545 TI - DNA fingerprinting of Enterococcus faecium by pulsed-field gel electrophoresis may be a useful epidemiologic tool. AB - Pulsed-field gel electrophoresis was used to compare 34 isolates of Enterococcus faecium from six different geographic locations. This procedure generated an average of 13 discernible fragment bands per isolate (range, 10 to 19 fragment bands) of 34 to 485 kb. The resulting restriction endonuclease digestion patterns were quite heterogeneous and were able to differentiate 27 of 34 isolates from each other, as defined by one or more mismatched fragment bands. Five patterns were shared by two or more isolates, and each set of isolates with matching patterns (shared pattern) originated in the same medical center, suggesting a common epidemiologic background, including highly penicillin resistant isolates in Richmond and Philadelphia. We conclude that pulsed-field gel electrophoresis of DNA digested with low-frequency-cleavage restriction enzymes offers a relatively simple method of comparing E. faecium for the purpose of epidemiologic study. PMID- 1757546 TI - Ability of National Committee for Clinical Laboratory Standards-recommended quality control strains from the American Type Culture Collection to detect errors in disk diffusion susceptibility tests. AB - The National Committee for Clinical Laboratory Standards (NCCLS) recommends, as a quality control for the disk diffusion susceptibility test, the use of three strains from the American Type Culture Collection: Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. This study assesses the capacity of these strains to detect errors in the overall method. ATCC strains were tested by comparing testing by the standard NCCLS recommended procedure (ST) with testing under the following conditions: incubation at 25 degrees C, Mueller-Hinton agar depths of 2 mm (AD2) and 8 mm (AD8), agar pHs of 6.5 and 8, inocula with McFarland standards of 0.25 (0.25M) and 4.0 McFarland (4.0M), direct inoculation without preincubation of inoculum (DI), and a 2-h delay between inoculation and disk application (2HR). The frequency of zone measurements outside the NCCLS-recommended control zone limits were as follows: ST, 0%; AD2, 18%; AD8, 9.6%; pH 6.5, 7.9%; pH 8, 5.3%; 0.25M, 3.5%; 4.0M, 24%; DI, 3.4%; 2HR, 1.8%; 25 degrees C (only E. coli and P. aeruginosa were evaluable), 28%. These results suggest that the quality control strains are only partially effective in detecting single extreme laboratory errors and that careful laboratory supervision is necessary even in the setting of properly monitored quality control strains. PMID- 1757547 TI - Comparison of the Vitek Immunodiagnostic Assay System with an indirect immunoassay (Toxostat Test Kit) for detection of immunoglobulin G antibodies to Toxoplasma gondii in clinical specimens. AB - The value and convenience of testing for specific anti-Toxoplasma gondii antibodies have led to the development of various antibody detection methods, such as the enzyme immunoassay. Two enzyme immunoassays, the Vitek Immuno Diagnostic Assay System (VIDAS; Vitek Systems, Hazelwood, Mo.) and the Toxostat Test Kit (TST; Whittaker Bioproducts, Walkersville, Md.), were compared for their ability to detect T. gondii immunoglobulin G antibodies in fresh human sera. Specimens were tested according to the instructions of each manufacturer. Of 304 serum specimens tested, the results for 282 (93%) agreed in both assays (77 were positive and 205 were negative). The results for the remaining 22 (7%) specimens were discrepant; 20 of the 22 specimens tested low positive or equivocal by Toxostat and negative by VIDAS. Upon retesting, 8 of these 22 specimens were in concordance, increasing the level of agreement to 95.3%. Intra-assay reproducibility was tested with four to nine replicates of each of seven samples (four positive, one negative, and two equivocal) by both tests and six replicates of one standard by VIDAS. Coefficients of variation (CVs) for VIDAS were 6, 8, 10, 15, 18, 19, and 23% for the samples and 14% for the standard. For Toxostat the CVs were 2, 8, 10, 10, 13, and 16%. In general, CVs for VIDAS were slightly larger than the CVs for Toxostat. Day-to-day variability over 3 days was tested by VIDAS for only six samples (three positive, two negative, and one equivocal) and four standards; CVs ranged from 2 to 15% for the samples and from 6 to 13% for the standards. In conclusions, VIDAS is a rapid, convenient, non-labor intensive, and easily performed test for the detection of immunoglobulin G antibodies to T. gondii in serum specimens. PMID- 1757548 TI - Babesia microti, human babesiosis, and Borrelia burgdorferi in Connecticut. AB - Babesia microti was isolated from a white-footed mouse (Peromyscus leucopus) that was captured in southeastern Connecticut in 1988, when the first human case of babesiosis acquired in Connecticut was recognized. To date, 13 cases of babesiosis have been reported in Connecticut, the largest number of human cases reported on the mainland United States. Two of nine patients quiried remembered a prior tick bite. Since Babesia parasites are known to be vectored only by ticks, we surmise that 12 of these infections were acquired via tick bites; 1 was obtained by blood transfusion (the patient was 46 years of age) from an endemically infected donor. The ages of the patients with tick-acquired babesiosis ranged from 61 to 95 years. Two patients died with active infections, and one patient died from chronic obstructive pulmonary disease soon after treatment with clindamycin and quinine. Indirect fluorescent-antibody titers of blood samples drawn at the time of hospitalization for 11 patients and at the time of active infection for 1 asymptomatic person ranged from 1:1,024 to 1:4,096. Five of eight patients with babesiosis also had significant immunoglobulin G or immunoglobulin M titers (1:640 to 1:5,120) to Borrelia burgdorferi. B. microti was isolated in Syrian hamsters inoculated with blood from 7 of 12 patients tested and was also isolated from mice captured in six towns. The peridomestic nature of the disease was demonstrated by isolating the parasite from white-footed mice captured in or near the yards of eight different patients. Of 59 mice tested, 27 were positive and 25 were coinfected with B. burgdorferi. The isolation of B. microti from a white-footed mouse captured in north-central Connecticut (West Hartford), away from the focus of human infections in southeastern Connecticut, suggests that this pathogen may spread into other areas where Ixodes dammini, the tick vector, becomes established. PMID- 1757549 TI - Yersinia enterocolitica isolated from two cohorts of young children in Santiago, Chile: incidence of and lack of correlation between illness and proposed virulence factors. AB - Yersinia enterocolitica was isolated from children in two cohorts in Santiago, Chile. In a cohort containing a cross section of children aged 0 to 4 years, Y. enterocolitica was isolated from stool samples of 1.1% of children with diarrhea and 0.2% of age-matched control children. In a subgroup of this cohort from which weekly stool samples were obtained from all children irrespective of clinical status, 6% of children had asymptomatic Yersinia infections. In a birth cohort (with a greater representation of children less than 1 year of age and a significantly higher rate of diarrhea), Y. enterocolitica was isolated from 1.9% of children with diarrhea and 0.6% of controls (P = 0.05). Biogroup 1A strains (which lacked traditional phenotypic and molecular markers for pathogenicity) were isolated from seven children with diarrhea but from no control children in the birth cohort (P = 0.02). All other isolates, including all isolates from asymptomatic children, were "pathogenic" strains in biogroup 4, serogroup O3; no association between these isolates and occurrence of disease was found. Y. enterocolitica is found among young children in Santiago, with asymptomatic infections not uncommon occurrences. However, questions about the association between previously described virulence factors and diarrheal illness remain. PMID- 1757550 TI - Serotyping of Canadian isolates of Treponema hyodysenteriae and description of two new serotypes. AB - A total of 30 isolates of Treponema hyodysenteriae collected in the Saint Hyacinthe (Quebec, Canada) area were serotyped by agar gel double immunodiffusion by using extracted lipopolysaccharide and hyperimmune rabbit antisera. Only 17% (5 of 30) of the isolates were typed with antisera specific for each of the seven known serotypes of T. hyodysenteriae. Antisera raised against 11 untypeable local isolates were then produced and tested against each lipopolysaccharide extract. Results showed two serologically distinct groups among 21 of the 25 untypeable isolates. The isolates in each group shared identical antigens. No detectable reactions could be observed between antisera raised against these 11 isolates and the antigens extracted from 7 reference serotype strains. On the basis of these results, two new serotypes of T. hyodysenteriae, serotypes 8 and 9, are proposed. We also propose isolate FM 88-90 as the reference strain for serotype 8 and isolate FMV 89-3323 as the reference strain for serotype 9. These two new serotypes, which represented 70% of the isolates tested, seem to be the major serotypes found in the province of Quebec. PMID- 1757551 TI - Rickettsiae and Borrelia burgdorferi in ixodid ticks. AB - Nymphs and adults of hard-bodied ticks were collected in Connecticut and tested by direct and indirect immunofluorescence staining methods for rickettsiae and Borrelia burgdorferi. Of the 609 Ixodes dammini ticks examined, 59 (9.7%) harbored rickettsialike microorganisms in hemocytes (blood cells). These bacteria reacted with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of with fluorescein-conjugated antiserum to Ehrlichia canis, the etiologic agent of canine ehrlichiosis. Prevalence of infection ranged from 6.8 to 12.7% for males and females, respectively. Although the specific identities of the hemocytic rickettsialike organisms are unknown, they share antigens with ehrlichiae. Electron microscopy revealed rickettsiae in ovarian tissues of I. dammini that also had infected hemocytes. Rickettsialike organisms were also observed in the hemocytes of 5 (6.9%) of 73 Dermacentor variabilis ticks. In analyses for B. burgdorferi, 146 (23.7%) of 617 I. dammini ticks harbored these spirochetes in midguts. Hemocytic rickettsialike microorganisms coexisted with B. burgdorferi in 36 (6.7%) of the 537 nymphs and adults of I. dammini examined. I. dammini, with its broad host range, has the potential to acquire multiple microorganisms. PMID- 1757552 TI - Sample preparation method for polymerase chain reaction-based semiquantitative detection of Leptospira interrogans serovar hardjo subtype hardjobovis in bovine urine. AB - An improved method of preparing bovine urine samples was developed for the rapid, specific, and sensitive detection of Leptospira interrogans serovar hardjo (subtype hardjobovis) DNA by the polymerase chain reaction (PCR). A total of 100 leptospire-free cows, 4 experimentally infected cows, and 2 negative control cows were used. PCR results were improved by (i) using 10-ml urine samples instead of 1-ml samples, (ii) adding 10(7) to 10(8) Leptospira biflexa serovar patoc cells as a carrier to each treated sample, (iii) preventing the loss of pelleted leptospires, and (iv) minimizing the presence of PCR-inhibiting factors in the samples. The preparation method enabled us to use the PCR to reproducibly detect as few as 5 to 10 leptospires per ml of urine without the need for dot blot hybridization. In addition, we were able to estimate the number of leptospires shed by experimentally infected cows. PMID- 1757553 TI - Use of monoclonal antibodies with neutralizing effects on toxic antigens from human bacterial plaque to detect specific bacteria by colony blotting. AB - Inflammatory periodontal diseases are provoked by bacteria which adhere to teeth at the gingival margin and form plaques containing toxins detectable by their effect on mammalian cells in culture. The aim of this study was to make toxin neutralizing monoclonal antibodies and determine whether they detect antigen in specific oral bacteria. Bacterial plaque was collected from teeth and homogenized, and the fluid phase (plaque extract) was boiled or first fractionated over Sephacryl S-300. Hybridomas from immunized mice secreted immunoglobulin M (IgM) antibodies which reacted to plaque antigens. Neutralization was detected by an increase in the growth of HL60 cells which were exposed to plaque toxins in the presence of IgM from hybridoma culture or ascitic fluids. However, the neutralization was obvious only when the plaque toxins reduced growth by 50% or less. Plaque toxin preparations were found to contain proteases which hydrolyzed all of the IgM in ascitic fluids within 24 h. Replenishing the IgM daily preserved protection compared with protection from IgM from other hybridomas or saline only. The decrease in the specific activity of plaque proteins caused by replenishing one such antibody (3hE5) was 2.5-fold compared with activity with unreplenished 3hE5, 3.8-fold compared with activity with saline only, and 10.7-fold compared with activity with replenished, unrelated antibody. The neutralizing IgM detected an array of 14,000- to 22,000 molecular-weight antigens. The native toxins may be aggregates of these antigens, or the array may indicate fragments of an undetected, larger antigen or a common, nonpeptide adduct. Only 0.5 to 0.8% of the bacteria from sites with periodontitis and grown on blood agar contained antigen. One group of reactive bacteria was identified as Actinomyces odontolyticus serotype I. Other isolates were identified as Staphylococcus epidermidis, but antigen disappeared from the these isolates within 6 weeks of subculture. Epitope-containing antigens were also found in streptococcal and Eikenella isolates, and it is likely that the antigens from only some of these bacteria are toxic. PMID- 1757554 TI - Phage typing of Salmonella enteritidis in the United States. AB - The number of reported isolates of Salmonella enteritidis has increased dramatically in the last 10 years. For many years phage typing has been a useful epidemiologic tool for studying outbreaks of S. typhi and S. typhimurium. In 1987, Ward et al. (L. R. Ward, J. De Sa, and B. Rowe, Epidemiol. Infect. 99:291 294, 1987) described a phage typing scheme for S. enteritidis. This system differentiated 27 phage types by use of 10 typing phages. With these phages, we typed 573 strains of S. enteritidis from humans (42 outbreaks), animals, food, and the environment. Ninety-six percent of the strains were typeable. The most common phage types were 8 (48.2%), 13a (20.1%), 13 (7.8%), and 14b (7.8%). Most of the strains were specifically collected from egg-related outbreaks in the northeastern United States in 1988 and 1989, probably accounting for the distribution of the four most common types in this sample. This system was particularly useful for differentiating a group of animal strains that had a number of diverse phage types. For 49 animal strains typed, 16 different patterns were obtained. Phage type 8 represented 32% of these strains, but no other phage type represented more than 8% of these strains. One-half of the 16 animal strains that were phage type 8 were from poultry. This phage typing system will be useful for comparing phage types found in the United States with those types encountered worldwide and for determining whether virulent strains of phage type 4 are entering the United States. Additional phage typing systems as well as molecular techniques are being studied to determine whether they can differentiate strains of phage types 8 and 13a. PMID- 1757555 TI - Fibronectin binding by Salmonella strains: evaluation of a particle agglutination assay. AB - Thirty-five Salmonella strains isolated from human cases of salmonellosis were tested and compared for their fibronectin (fn) binding capacities by using two fn particle agglutination assays (fn-PAAs) prepared by coating with human fn either (i) latex beads (Difco; 0.81-micron diameter) (L-fn-PAA) or (ii) heat-killed formalin-treated Staphylococcus aureus Cowan 1 cells (C-fn-PAA). Six S. aureus strains were also included in this study as controls. The strains were cultured on colonization factor antigen agar and blood agar and in tryptic soy broth and brain heart infusion broth. The Salmonella and S. aureus strains were cultured at 33 and 37 degrees C, respectively, for optimal expression of fn-binding proteins. Bacterial cells (approximately 10(10) cells per ml) harvested from growth in various culture media and suspended in 0.02 M potassium phosphate buffer (pH 6.8) agglutinated the fn-PAA reagents. These reactions were scored semiquantitatively from + to + depending on the speed or intensity of the reactions within 2 min. Maximum agglutination in fn-PAA systems was observed when the cells were grown in brain heart infusion broth, while tryptic soy broth proved to be least suitable media for culturing cells for fn-PAAS. Although a statistically highly significant correlation was obtained between results of assays of radiolabeled fn and 29-kDa fragment binding, no significant correlation was observed (i) between the results of strains cultured in different media or (ii) when semiquantitative score results of the two fn-PAA systems were compared with those of the conventional radiolabeled fn assay. To enhance the efficiency of the test system, the C-fn-PAA reagent was stained with methylene blue (2% in 0.17 M glycine-NaOH buffer [pH 6.8]). This facilitated easy interpretation of results, which could be performed on hydrophobic paper instead of glass slides. The results obtained with both unstained C-fn-PAA and stained C-fn-PAA were comparable to each other and reproducible. Although the fn-PAAs are simple and easy to perform, the results did not differentiate between negative, low, moderate, and high binding abilities when Salmonella strains were evaluated for fn binding, and the results were not comparable to those obtained by the conventional radiolabeling method. PMID- 1757556 TI - Evaluation of liquid media for growth of Helicobacter pylori. AB - Helicobacter pylori has routinely been isolated and grown on solid media. Recently, we have succeeded in obtaining growth of this organism in several liquid media in large volumes, including tryptic soy broth, Mueller-Hinton broth, brucella broth, brain heart infusion broth, and Columbia broth. Growth was tested in the media with and without supplementation. Growth was obtained after incubation under microaerobic conditions and with CO2 enrichment. Growth in a stationary system versus that in an agitated system was evaluated. Results from these experiments show that H. pylori can be grown in any of the liquid media tested except buffered yeast extract-alpha-ketoglutarate if serum is added. No growth was observed on buffered yeast extract-alpha-ketoglutarate even with serum and other supplementation. Growth of H. pylori in most of the liquid media with supplements was improved if the culture was incubated in a CO2 atmosphere. The findings reported here may be useful in clinical, industrial, and research laboratories that require harvests of large quantities of H. pylori cells. PMID- 1757557 TI - Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. AB - The bacterial 16S rRNA genes from blood samples of two patients with human ehrlichiosis and from an isolate recovered from one of the patients were amplified by using the polymerase chain reaction. The amplimers were then cloned and sequenced. The 16S rRNA gene sequence was also determined for Ehrlichia canis (two strains), E. equi, E. phagocytophila (two strains), and E. sennetsu (two strains). These sequences, along with a previously published 16S rRNA gene sequence of E. risticii, were compared. The 16S rRNA gene sequences were identical for all three sources of the human ehrlichiosis agent. The sequence comparisons indicate that the human ehrlichiosis agent is a new species most closely related to E. canis (98.2%) and more distantly related to other Ehrlichia spp. We propose that this species be named Ehrlichia chaffeensis sp. nov., with the Arkansas strain as the type strain. PMID- 1757558 TI - Aerokey II: a flexible key for identifying clinical Aeromonas species. AB - A small subset (n = 18) of highly discriminatory tests was derived from the feature frequency of 50 tests used in the study of 167 predominantly clinical Aeromonas strains. Seven of these eighteen tests were used to construct a flexible, dichotomous key, Aerokey II, for identifying clinical aerontonads: esculin hydrolysis, gas from glucose, acid from arabinose, indole production, acid from sucrose, Voges-Proskauer reaction, and resistance to cephalothin (30 micrograms). This schema was initially evaluated in a single-blind trial of 60 well-characterized clinical Aeromonas hydrophila (n = 21), A. caviae (n = 19), and A. veronii bv. sobria (n = 20) strains from an independent laboratory. Of the 60 strains tested, 58 (97%) were accurately identified to the species level. Aerokey II was further evaluated with 18 additional American Type Culture Collection and reference strains representing the more recently proposed taxa A. veronii bv. veronii, A. schubertii, A. jandaei, and A. trota and accurately identified all of these strains. PMID- 1757559 TI - Use of multiple markers for investigation of an epidemic of Shigella sonnei infections in Monroe County, New York. AB - Antibiotic susceptibility patterns, plasmid profiles, and endonuclease restriction analysis of plasmid DNA were used in the investigation of an epidemic of Shigella sonnei infections in Monroe County, New York, in 1988 and 1989. The epidemic peaked during the winter, included the simultaneous transmission of the disease from person to person and from common food sources, and especially affected inhabitants of the poor, inner-city neighborhoods, young children of both sexes, and women. Resistance to ampicillin, tetracycline, or trimethoprim sulfamethoxazole, encoded in a 70-MDa plasmid, was found in most of the examined isolates. Unexpectedly, isolates from patients involved in a food-borne outbreak exhibited three different antibiotic susceptibility patterns, suggesting deletion of antibiotic resistance determinants in some strains. Antibiograms clearly separated food-borne outbreak-related and non-foodborne outbreak-related strains, distinguished more strains than did the plasmid profiles, and were useful in tracing the dissemination of individual isolates in the community. Restriction endonuclease analysis substantially increased the discriminatory value of plasmid profiles and validated the antibiogram results. The present study illustrates the complexity of epidemics of S. sonnei infections and shows the value of combining different biological markers in the investigation. PMID- 1757560 TI - Evaluation of a commercial measles virus immunoglobulin M enzyme immunoassay. AB - Paired serum samples from 93 patients suspected of having measles were assayed for measles virus-specific immunoglobulin M (IgM) antibodies by an enzyme immunoassay (EIA), and the results were compared with results from a complement fixation assay and an EIA for measles virus IgG. By using significant serologic rises as the standard for comparison, the IgM EIA assay had a sensitivity of 85.7%, a specificity of 81.3%, a positive predictive value of 95.7%, and a negative predictive value of 54.2%. This assay can be expected to perform well in outbreak situations. PMID- 1757561 TI - Yersinia enterocolitica: a frequent seasonal stool isolate from children at an urban hospital in the southeast United States. AB - From 1 December 1988 through 28 February 1991, 7,290 rectal swab specimens received in our laboratory were screened for Yersinia enterocolitica. A total of 76 patients had Y. enterocolitica isolated from their stool samples. Of these patients, 59 (77.6%) were 12 months old or younger. Y. enterocolitica was second only to Salmonella spp. in this age group. Routine screening for Y. enterocolitica may be warranted in hospitals serving large pediatric populations. PMID- 1757562 TI - Evaluation of the Vitek GPS-TA card for laboratory detection of high-level gentamicin and streptomycin resistance in enterococci. AB - The Vitek GPS-TA card (Vitek Systems, Hazelwood, Mo.) was compared with single concentration broth microdilution and disk diffusion methods using high-content disks for the detection of high-level resistance to gentamicin and streptomycin in 99 isolates of enterococci (81 Enterococcus faecalis isolates and 18 Enterococcus faecium isolates). The GPS-TA card accurately detected high-level resistance to gentamicin, but not streptomycin, in E. faecalis. When streptomycin is being considered for therapy, either disk diffusion or time-kill studies should be used to confirm susceptible results obtained by Vitek testing. Additional studies are needed to determine the best method for testing E. faecium isolates. PMID- 1757563 TI - Evaluation of a new method for identification of Cryptococcus neoformans which uses serologic tests aided by selected biological tests. AB - A new method for identifying Cryptococcus neoformans isolates and their serotypes by the slide agglutination test using five kinds of factor sera, with the aid of nitrate reduction, phenol oxidase, and growth at 37 degrees C tests was evaluated by using 36 reference strains and 75 clinical isolates of C. neoformans. The results showed that the reference strains were identified exactly as they were labeled, and clinical isolates were identified as C. neoformans serotypes A, D, and AD. C. neoformans could be distinguished from other Cryptococcus species that cross-reacted with factor sera by their ability to grow at 37 degrees C. These results indicate that the slide agglutination test combined the use of factor sera for isolates which grow at 37 degrees C is a useful method for identification of C. neoformans and their serotypes and that the nitrate reduction test (negative in 100% of the isolates) and the phenol oxidase test (positive in approximately 95% of the isolates) can be used to confirm that the species is C. neoformans. PMID- 1757564 TI - Glycosidase profiles of members of the family Enterobacteriaceae. AB - A total of 712 strains representing 47 taxa of the family Enterobacteriaceae were tested for the ability to hydrolyze 14 4-methylumbelliferyl (4-MU)-linked substrates within 3 h of incubation. In addition to the well-known differentiation potential of the hydrolysis of 4-MU-beta-D-galactopyranoside, 4 MU-beta-D-glucuronide, and 4-MU-beta-D-xylopyranoside, the hydrolysis of some other fluorogenic substrates (e.g., 4-MU-beta-D-fucopyranoside, 4-MU-N-acetyl beta-D-galactosaminide, and 4-MU-alpha-D-galactopyranoside) can also be used for species differentiation within the family Enterobacteriaceae. PMID- 1757565 TI - Emergence of homogeneously methicillin-resistant Staphylococcus aureus. AB - Forty-seven clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), collected between 1986 and 1990 from 29 institutions, were analyzed for susceptibility to various antibiotics. Twenty-six strains were homogeneously methicillin resistant (i.e., greater than or equal to 10% of the cells in these strains were able to grow on Mueller-Hinton agar containing 50 micrograms of methicillin per ml). The MICs of gentamicin, clindamycin, trimethoprimsulfamethoxazole, methicillin, and imipenem for homogeneous MRSA strains were higher than those for heterogeneously resistant strains. Both types of strains were, for the most part, susceptible to vancomycin and trimethoprim sulfamethoxazole. Ciprofloxacin-resistant MRSA strains were not isolated prior to 1988 but made up 40% of the post-1987 strains. The level of methicillin resistance correlated well with the imipenem MIC, suggesting that susceptibility to imipenem may serve as a marker to identify and monitor the prevalence of homogeneous MRSA strains. PMID- 1757566 TI - Characterization of yellow-pigmented enterococci from severe human infections. AB - Four strains of yellow-pigmented enterococci that resembled the species Enterococcus casseliflavus were isolated from patients who had undergone surgical treatment. They were substantially homologous in terms of biochemical properties, antibiotic susceptibilities, and plasmid DNA profiles. Yellow-pigmented enterococci could be another potentially important cause of nosocomial infection in surgical units. PMID- 1757567 TI - Prevalence of virulent Rhodococcus equi in isolates from soil and feces of horses from horse-breeding farms with and without endemic infections. AB - The prevalence of virulent Rhodococcus equi in isolates from soil and feces of foals on a farm with endemic R. equi infections was significantly higher than that of a farm with no history of the disease. Foals bred on a farm with the endemic disease might be constantly exposed to virulent R. equi in their environment. PMID- 1757568 TI - Disk diffusion susceptibility test interpretive criteria for GR69153, a new catechol-substituted cephalosporin. AB - GR69153 disk diffusion tests with 10- and 30-micrograms disks were evaluated against 383 rapidly growing aerobic pathogens. Very high absolute agreement (96.1 to 98.1%) was observed between the MICs and disk zone diameters, and no false susceptible results were encountered with the proposed criteria. The 30 micrograms GR69153 disk with a susceptible-zone diameter of greater than or equal to 17 mm (MIC correlate, less than or equal to 8 micrograms/ml) and a resistant zone diameter of less than or equal to 13 mm (MIC correlate, greater than 16 micrograms/ml) is recommended. GR69153 had a spectrum of activity slightly wider than that of ceftazidime against the species tested. PMID- 1757569 TI - Diagnosis of Legionnaires' disease by radioimmunoassay of Legionella antigen in pleural fluid. AB - We describe a case of culture-proven Legionnaires' disease (serogroup 1) in which a rapid diagnosis was made by detection of Legionella antigen in pleural fluid by use of the Binax radioimmunoassay for urine. PMID- 1757570 TI - Comparison of commercially available group B streptococcal latex agglutination assays. AB - Detection of group B streptococcus (GBS) antigen in urine by latex particle agglutination (LPA) may facilitate the rapid diagnosis of GBS sepsis. We sought to compare three commercial LPA assays with specimens that were spiked with type specific antigen, group-specific antigen, or type III organisms. There were sensitivity differences between the assays, but the Bactigen assay performed best, detecting as little as 1 ng of GBS group-specific antigen per ml in urine and as few as 10(5) CFU of GBS type III organisms per ml in urine, serum, and cerebrospinal fluid. PMID- 1757571 TI - Detection of antibodies to Mycoplasma gallisepticum in egg yolk versus serum samples. AB - Serum (n = 1,636) and egg yolk (n = 802) samples collected from hens on four commercial egg farms in Florida were tested for the presence of specific antibodies to Mycoplasma gallisepticum in a commercially available enzyme-linked immunosorbent assay. No significant differences were noted between serum and egg yolk samples with respect to distribution of positive, suspect, and negative test results or for the mean sample/positive control ratio values of positive, suspect, and negative test results. A linear relationship between the distribution of positive and negative results and the age of the birds was observed for results obtained with both serum and egg yolk samples. On the basis of the results of this study, egg yolk samples can be used in lieu of serum samples to screen flocks for antibodies to Mycoplasma gallisepticum. PMID- 1757572 TI - Isoprenoid quinones of "Afipia" spp. AB - The isoprenoid quinone contents of seven strains of "Afipia felis," the type strains of "A. clevelandensis" and "A. broomeae," and reference strains of three unnamed "Afipia" genospecies were determined by reverse-phase high-performance liquid chromatography. The quinone profiles of all "Afipia" strains were essentially identical, with ubiquinone 10 as the major component. The identity of ubiquinone 10 was confirmed by mass spectrometry. PMID- 1757573 TI - Evaluation of the Roche Septi-Chek AFB system for recovery of mycobacteria. AB - The Septi-Chek AFB system for the recovery of mycobacteria from clinical specimens was compared with a conventional approach using Lowenstein-Jensen and Middlebrook 7H11 agars. A total of 1,532 clinical specimens were analyzed; 132 yielded mycobacteria. Mycobacterium tuberculosis and Mycobacterium avium complexes were the predominant isolates. With the conventional combination of Lowenstein-Jensen and 7H11 agars, 75.8% of the isolates were recovered; the Septi Chek AFB allowed recovery of 100% of the isolates. Septi-Chek AFB required less time for the detection of mycobacteria than did the conventional media. PMID- 1757574 TI - Diagnosis of Chlamydia trachomatis cervical infection by detection of amplified DNA with an enzyme immunoassay. PMID- 1757575 TI - Thought disorder and verbal recall in acutely psychotic patients. AB - This study examined the relationship between thought disorder and verbal recall in schizophrenic, manic, and schizoaffective inpatients. Based on previous research, it was predicted that subjects who demonstrated only positive thought disorder would differ from those with positive and negative thought-disorder in terms of their ability to encode short descriptive passages. Unlike controls, who were able to encode organized material better than unorganized material, neither thought-disorder group improved its encoding when the material to be remembered was more organized. Both thought-disorder groups remembered more when the material was less organized. These findings raise a number of issues with regard to the interrelationship among thought disorders, psychiatric diagnoses, and information-processing deficits. PMID- 1757576 TI - The perception of attractiveness: what about the beholders? AB - This study asked whether there is a relationship between heterosexually relevant dimensions and perception of female attractiveness and femininity. Two hundred and forty-nine undergraduate males rated 22 photographs of young women on these two dimensions. Seventy-nine of these subjects also took the Macho Scale, the Survey of Heterosexual Interactions, and the Bem Sex Role Inventory. Results showed that high Macho subjects viewed most of the photographed women as less attractive than low Macho subjects did. Masculinity/femininity and heterosexual anxiety showed less of a relationship. As predicted, moderately attractive women were described most differently by the high Macho/low Macho raters. PMID- 1757577 TI - Comparison of factor-analyzed Adolescent Reinforcement Survey Schedule (ARSS) responses from Japanese and American adolescents. AB - The Adolescent Reinforcement Survey Schedule (ARSS) was administered to a sample of male and female late adolescent college students from Japan (N = 500). The responses to the ARSS are factor analyzed using a principal component method. The results of the factor-analyzed ARSS from the Japanese sample are compared and contrasted with the results from a previous study (Holmes et al., 1987) in which ARSS was administered to a sample of American male and female college students (N = 231). Both the American and Japanese samples produced 10 interpretable factors. A recommendation is made to replicate the present study with groups of early and mid-adolescents in each culture in order to study shifts in reinforcers during different periods of adolescent development. PMID- 1757578 TI - The Multidimensional Scale of Perceived Social Support: a confirmation study. AB - This study examined the psychometric properties of the Multidimensional Scale of Perceived Social Support (MSPSS; Zimet, Dahlem, Zimet, & Farley, 1988) with a diverse group of 154 students at an urban college. The following areas were investigated: internal reliability, factorial validity, social desirability bias, and the moderating effect of social support between stressful life events and depression (i.e., the buffering hypothesis). The MSPSS had good internal reliability, and the factor analysis confirmed the subscale structure of the measure: family, friends, and significant other. There was no indication that social desirability bias influenced subjects' responses. Finally, social support was related to depression only for those subjects who were experiencing high levels of life stress, which lends support for the buffering hypothesis. PMID- 1757579 TI - Prediction of intention to exercise of individuals who have suffered from coronary heart disease. AB - The aim of the study was to understand the intention to exercise of individuals who suffer from CHD. A group of 161 cardiac patients completed a questionnaire that investigated intentions, attitudes, subjective norms, perceived barriers, habits, perceived difficulties, and personal normative beliefs with respect to exercising, as well as perceived severity of and perceived vulnerability to re infarction. Regression of intention yielded an R2 of .41 (p less than .0001), with perceived barriers, habits, and perceived difficulties as the significant predictors. MANOVA indicated that high and low intenders differed (p less than .01) according to their perception of three barriers: difficulties in time management, difficulties in psychological adaptation, and laziness. These results suggest that new guidelines should be adopted for the development of cardiac rehabilitation exercise programs. PMID- 1757580 TI - An investigation of the relationship between self-report of memory functioning and memory test performance. AB - Memory complaints are some of the most common cognitive problems presented to clinical psychologists and neuropsychologists. However, the probable validity of memory complaints presented to a psychologist rarely has been validated by objective memory tests. Using the Memory Functioning Questionnaire (MFQ; Gilewski et al., 1983), 62 relatively young adults reported the extent to which they were experiencing various types of memory problems. These data were compared with findings of memory and non-memory tests on an expanded Halstead-Reitan test battery and with the MMPI/MMPI-2. Results showed that with the exception of persons with more than one MMPI/MMPI-2 evaluation, memory complaints were not related more to memory than to non-memory tests. PMID- 1757581 TI - Mothers of sexually abused children: an MMPI study. AB - Thirty-seven mothers of sexually abused children were contrasted with 41 mothers who were receiving outpatient psychotherapy and with 76 women with no history of psychiatric disturbance on the MMPI. The groups were matched on age and socioeconomic status, and significant between-group differences were noted. Outpatients and mothers of sexually abused children were significantly more elevated than the normal comparison group on the majority of the scales. Mothers of sexually abused children differed from psychiatric outpatient mothers on several scales. The 4-3 and spike 4 MMPI code-types were significantly more common in mothers of sexually abused children than in outpatient mothers. Differences in the child's sexual abuse characteristics were related to MMPI scales of the mother. PMID- 1757582 TI - Borderline, depressive, and schizophrenic discrimination by MMPI. AB - This study intended to differentiate among borderline personality disorder (BPD), schizophrenic, and depressed patients on the basis of their MMPI profiles. MMPI profiles of 237 psychiatric inpatients were selected on the basis of their primary DSM-III admission diagnoses. Analysis of MMPI mean scores and discriminant function analysis supports previous literature in describing borderline patients as having a broad spectrum of psychopathology typified by an attitude of alienation and rebelliousness, atypical thought content and/or process, and eccentric behavior. Schizophrenic patients are differentiated from BPD patients by the presence of thought disorder and psychotic-like manifestations. The depressed patients did not show the aforementioned extreme characteristics of the other two groups. PMID- 1757583 TI - Effect of repeated administration of a neuropsychological battery in the elderly. AB - Our study explored the magnitude of practice effect in repeated administration of NP measures that tap different cognitive domains in normal elderly subjects (N = 122) between ages 57 and 85, who were evaluated over three annual testing probes. Results revealed that WAIS-R PIQ, serial recall of words, WMS visual memory, and memory for logical passages (immediate and delayed) are likely to improve on the retest due to practice effect in individuals below age 75, whereas test-retest changes in older people show a different pattern. Implications of age-specific changes on retest for differential diagnosis of dementia in clinical practice were considered. PMID- 1757584 TI - Is the pattern of intellectual growth and decline across the adult life span different for men and women? AB - Gender comparisons on the WAIS-R were made for 1,480 adults from the standardization sample, ages 20-74 years, to determine whether men and women differ in their age-related patterns of change on tests of fluid and crystallized abilities. Multivariate analyses of covariance and univariate analyses of covariance were conducted, covarying education, to examine the age + gender interactions. These interactions tended to be nonsignificant and trivial for the WAIS-R Verbal and Performance scales and the 11 subtests, which suggests that both men and women maintain their crystallized abilities through old age, but show early, rapid declines in fluid ability. These results were interpreted in terms of the literature on aging and intelligence, gender differences in cognitive abilities, and gender differences in V-P patterns for patients with unilateral brain damage. PMID- 1757585 TI - Subliminal psychodynamic activation, food consumption, and self-confidence. AB - The subliminal psychodynamic activation (SPA) method was used to study the effects of a message related to loss and separation on the behavior of anaclitic and control subjects in a sample of male college students (N = 148). In the subliminal condition (4 ms exposure time), subjects shown the experimental message "Mommy is Leaving Me" ate significantly fewer crackers than those exposed to the neutral message "Mona is Loaning It" (p = .04). Subjects subliminally exposed to the experimental message reported less confidence in their interpersonal attractiveness than those subliminally shown the neutral stimulus (p = .05). These findings, which support the hypothesis that semantic analyses are performed unconsciously, are discussed in the context of recent research on both the SPA paradigm and the anaclitic personality. PMID- 1757586 TI - Evaluation of a predoctoral clinical psychology internship program by intern graduates. AB - This investigation is a replication and extension of an earlier study by Stout, Holmes, and Rothstein (1977) of the predoctoral clinical psychology intern graduates at the William S. Hall Psychiatric Institute. The interns were surveyed (N = 63) with regard to how adequately their internship experience prepared them for their current professional work as practicing clinical psychologists. Questionnaire data (n = 44) from graduates are analyzed in terms of the demographics of each intern's work situation, ratings of how well their internship prepared them in the areas of interprofessional relationships, teaching psychodiagnostic evaluations, psychological treatment, administration, consultation, and research. Several recommendations are offered by the intern graduates for refinement of the clinical psychology internship. PMID- 1757587 TI - Characteristics common to females who exhibit anorexic or bulimic behavior: a review of current literature. AB - This paper reviews recent literature on the characteristics of females who exhibit anorexic or bulimic symptoms. Although researchers categorize bulimics as either binge/restrictors or binge/purgers, this paper does not distinguish between the two with regard to characteristics. Personal, cognitive, and physical characteristics, as well as external influences, are examined for each. An additional purpose of the paper is to provide an overview of risk factors that may predispose an individual to bulimia nervosa or anorexia nervosa. PMID- 1757588 TI - A self-discrepancy reduction model of religious coping. AB - It was proposed that effectiveness of a religious response to personal crisis is related to type and amount of self-discrepancy. Fifty subjects were administered a questionnaire to assess the following two types of self-discrepancies: (1) discrepancy between perceived actual self and perceived ideal self and (2) discrepancy between perceived actual self and perceived ought-to-be self. Subjects also were asked to choose types of religious responses to a personal crisis. Religious responses were behaviorally, cognitively, and affectively loaded. Subjects with an actual/ought discrepancy chose behavioral and affective religious responses more frequently than did those without this discrepancy. No effects were found for the actual/ideal discrepancy. Implications of these results for revision and extension of the model are discussed. PMID- 1757589 TI - Enhancement of physicians' treatment of illness by behavior therapy. AB - The author criticizes physicians who cling to the conventional belief that successful diagnosis and treatment of physical symptoms can only be handled by medical interventions. He describes the behavioral treatment of three patients who had been treated for almost two years unsuccessfully by medical specialists and who improved significantly with behavioral interventions. A physician who lacks the psychological information that illuminates the environmental and personal contingencies that help to initiate, support, and maintain a patient's symptoms--information such as that obtained by a behavioral analysis--risks deriving a deceptive image of the illness, extends treatment time, prolongs suffering, augments the risk of iatrogenic complications, and increases treatment costs. PMID- 1757590 TI - Cognitive-behavior therapy with nighttime fearful children. AB - In this study, the nighttime problems of two girls diagnosed as having separation anxiety disorder were treated with cognitive-behavioral procedures. Through the use of a multiple baseline design across subjects, the additive effects of self control training and self-control training plus contingent reinforcement were determined. For both girls, self-report of anxiety and behavioral avoidance of sleeping in their own beds was reduced significantly only when to the self control training the reinforcement condition was added. Resolution of these nighttime problems also appeared to generalize to other features of separation anxiety disorder. The clinical and theoretical significance of these findings is discussed. PMID- 1757591 TI - Phone phobia, phact or phantasy? An operant approach to a child's disruptive behavior induced by telephone usage. AB - The clinical efficacy of a contingency management program for treating a developmentally disabled girl referred for telephone phobia was evaluated using both a multiple baseline across settings design and a reversal design. A descriptive analysis indicated that the 'phobia' was in all probability an operant, rather than a respondent. The treatment, consisting of differential reinforcement, extinction and time-out, was effective in reducing the frequency and intensity of disruptive behaviors in response to telephone usage. Follow-up assessments at 1, 3, and 6 months revealed that treatment gains were maintained. PMID- 1757592 TI - Intervention package for treating sleep disorders in a four-year-old girl. AB - The study describes an intervention package for the treatment of sleep disorders in a 4-year-old girl, using a multiple-baseline design. The subject's sleep disorders included several undesirable habits: never going to sleep in her own bed; waking up several times during the night, screaming and shouting for hours; and entering her parents' bed and insisting on staying there. The intervention package was carried out with the parents, the child, and her sister. It was based on the disconnection of the contingencies between behavior and outcome; rewards; praise; and time-out. The whole process was terminated in 8 weeks, and maintenance levels were assessed via follow-up after three and six months. PMID- 1757593 TI - The practice of behavior therapy among clinical psychologists in Hong Kong. AB - A survey was conducted to assess the extent to which behavior therapy techniques were employed by clinical psychologists in Hong Kong. The most popular techniques included those that could be grouped under the self-management package and the least popular techniques generally involved an aversive element, or were in vivo. The use of behavior therapy was correlated with the younger age range of the treatment clientele. The results and the future development of behavior therapy were discussed in terms of cultural issues, training and the theoretical orientations of the respondents. PMID- 1757594 TI - Managed mental health care and effective psychotherapy: a step in the right direction? AB - Although a substantial body of literature indicates that specialized treatments, usually of a behavioral nature, are available with comparatively superior outcome, much of this information is clinically under-utilized across a wide range of disorders. Until recently, there were few incentives for clinicians to apply state-of-the-art procedures to their clients' problems. Sweeping changes in the health insurance industry, however, are leading to a proliferation of managed mental health care companies driven by economic forces to deliver the most effective and efficient (and therefore most profitable) forms of care. The present paper discusses the history and development of these insurance changes and their implications for the future utilization of behavior therapy. PMID- 1757595 TI - The long-term habituation of sexual arousal in the human male. AB - Long-term habituation of male sexual arousal occurs when (a) short-term (intrasession) habituation occurs; (b) habituated arousal spontaneously recovers; (c) the magnitude of spontaneous remission decreases across habituation sessions; and (d) the number of trials to habituation decreases across sessions. Five undergraduate volunteers each had six sessions at one week intervals of 15 presentations of erotic audiotapes. For three weeks, the same audiotape was presented, and for each of the other three sessions a different audiotape was presented at every stimulus trial. As indicated by penile plethysmography and self-report, in the constant stimulus conditions the criteria for long-term habituation generally were met. By contrast, responses to variable stimuli remained consistently high. Theoretical and clinical implications of the habituation process are discussed. PMID- 1757596 TI - EMG biofeedback treatment of pediatric hyperfunctional dysphonia. AB - A 9-year-old boy with a long history of impaired communication resulting from hyperfunctional dysphonia and vocal nodules had proven to be unresponsive to traditional voice therapy. In this study, he engaged in biweekly visual EMG biofeedback training to reduce laryngeal muscle tension. In a multiple baseline design across two responses with changing criteria, results demonstrated sequential stepwise reductions in muscle tension with each new criterion. Concomitant improvements were found in laryngeal aerodynamic functioning and in voice quality. The treatment also resulted in the elimination of the vocal nodules without surgical intervention. These effects were maintained at 6 month follow-up. PMID- 1757597 TI - Architecture of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey. AB - The agranular frontal cortex is formed by several distinct functional areas. There is no agreement, however, on its cytoarchitectonic organization. The aim of this study was to redefine the cytoarchitectonic organization of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey. A particular goal was to find out whether the so-called supplementary motor area (SMA) is cytoarchitectonically different from the rest of area 6 and whether it can be considered as a single, independent cytoarchitectonic area. The results showed that, rostral to F1 (area 4), four architectonic areas can be recognized in the superior (dorsal) and mesial area 6. Two fo them are located on mesial cortical surface (F3 caudally and F6 rostrally) and two on superior cortical convexity (F2 caudally and F7 rostrally). The main cytoarchitectonic features of the five identified areas can be summarized as follows. F1: (1) giant pyramidal cells organized in multiple rows, (2) columnar pattern extending from the white matter to the superficial layers, (3) low cellular density in the lower part of layer III. F3: (1) high cellular density in the lower part of layer III, which fuses with a dense Va, (2) columnar pattern present only in the deepest layer, (3) occasional presence of giant pyramidal cells in layer Vb. F6: (1) prominent layer V, (2) absence of sublayer Vb, (3) homogeneous cell density in superficial layers. F2: (1) thin row of medium-size pyramids in the lowest part of layer III, (2) columnar pattern extending to the superficial layers, (3) dense layer Va, (4) few, scattered giant pyramids in layer Vb. F7: (1) prominent layer V, (2) bipartite layer VI. Areas F1, F2, and F3, as defined cytoarchitectonically, coincided with the homonymous histochemical areas. The present data showed also that area 24 is formed by four subareas: 24a, b, c and d. Areas 24a and b occupy the ventral part of area 24, whereas its dorsal part is formed by area 24c, located rostrally, and area 24d, located caudally. The following features distinguish area 24d from area 24c: (1) larger pyramidal cells in layer V, (2) presence of medium-size pyramidal cells in the lower part of layer III, (3) more prominent columnar pattern, (4) higher myelinization with the presence of an evident horizontal plexus. Mesial area 6 is usually considered as a single functional entity (SMA). Our findings show that this cortical region is formed by two distinct cytoarchitectonic areas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1757598 TI - Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex: an intracortical microstimulation study in the macaque monkey. AB - The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electrical microstimulation. Our main purpose was to find out whether the cytoarchitectonic subdivision of the mesial agranular frontal cortex into two areas has a physiological counterpart. The result showed that F3 (the caudal area) contains a complete motor representation with hindlimb movements located caudally, forelimb movements located centrally, and orofacial movements located rostrally. The great majority of limb movements involved proximal joints. With respect to F1, F3 showed the following functional characteristics: (1) lack of segregation between proximal and distal movements, (2) larger percentage of complex movements, and (3) higher excitability threshold. Movements were more difficult to elicit from F6 (the rostral area) than from F3. However, by using a longer stimulus train duration (100 ms) 39.3% of tested sites produced body movements. This percentage increased (50.5%) when the electrical stimulation was applied during monkey natural movements instead of when the monkey was still in its chair. Most of the evoked movements concerned the forelimb. More rarely, neck and upper face movements were observed. Unlike F1 and F3 where most movements were fast, slow movements were frequently observed with stimulation of F6. Many of them mimicked natural movements of the animal. Eye movements were evoked from F7 (superior area 6) but not from F6. An additional motor representation was found in the dorsocaudal part of area 24 (24d). This area is topographically organized with a forelimb representation located caudally and ventrally and a hindlimb representation located rostrally and dorsally. The excitability threshold of area 24d is higher than that of F1 and F3. Evoked movements were occasionally observed also after stimulation of area 24c. In conclusion, on the mesial cortical wall rostral to F1, there are at least three independent motor representations. On the basis of somatotopic organization and excitability properties, we propose that the term supplementary motor area (SMA-proper) should be reserved to F3. PMID- 1757599 TI - Projections from the posteroventral cochlear nucleus to the superior olivary complex in guinea pig: light and EM observations with the PHA-L method. AB - The efferent neural projections from posteroventral cochlear nucleus to the superior olivary complex in guinea pig were examined with the Phaseolus vulgaris leucoagglutinin anterograde tract-tracing method. Light microscopic analysis demonstrated that the posteroventral cochlear nucleus of guinea pig bilaterally projects to the superior para-olivary nucleus and the rostral, medioventral, and lateroventral peri-olivary regions. Ipsilaterally, the posteroventral cochlear nucleus projects to the lateral superior olive, the caudal peri-olivary region, and areas immediately surrounding the capsule of the lateral superior olive. Contralaterally, the posteroventral cochlear nucleus projects to the medial nucleus of the trapezoid body. All of these projection axons travel in the trapezoid body and their terminals make, primarily, en passant endings upon their targets. Exclusively within the contralateral medial nucleus of the trapezoid body, some neurons terminate also in calyceal endings. The assumption that immunolabeled structures observed with light microscopy made actual synaptic contact in their respective target areas was confirmed with electron microscopy. With postembedding immunocytochemical procedures applied to thin sections, the electron microscope revealed labeled synaptic vesicles and pre- and postsynaptic membrane specializations. The projection pattern from posteroventral cochlear nucleus was found to be topographically organized in three distinct regions. The more dorsally located neurons of the posteroventral cochlear nucleus terminated dorsomedially in the ipsilateral lateral superior olive, ventromedially in the contralateral superior para-olivary nucleus, and medially in the contralateral medioventral peri-olivary region. The more ventrally located neurons of the posteroventral cochlear nucleus terminated dorsolaterally in the ipsilateral lateral superior olive, dorsolaterally in the contralateral superior para-olivary nucleus, and laterally in the contralateral medioventral peri-olivary region. PMID- 1757600 TI - Generation patterns of immunocytochemically identified cholinergic neurons at autonomic levels of the rat spinal cord. AB - The time at which a neuron is "born" appears to have significant consequences for the cell's subsequent differentiation. As part of a continuing investigation of cholinergic neuronal development, we have combined ChAT immunocytochemistry and [3H]thymidine autoradiography to determine the generation patterns of somatic and autonomic motor neurons at upper thoracic (T1-3), upper lumbar (L1-3), and lumbosacral (L6-S1) levels of the rat spinal cord. Additionally, the generation patterns of two subsets of cholinergic interneurons (partition cells and central canal cluster cells) were compared with those of somatic and autonomic motor neurons. Embryonic day 11 (E11) was the first day of cholinergic neuronal generation at each of the three spinal levels studied, and it also was the peak generation day for somatic and autonomic neurons in the upper thoracic spinal cord. The peak generation of homologous neurons at upper lumbar and lumbosacral spinal levels occurred at E12 and E13, respectively. Somatic and autonomic motor neurons were generated synchronously, and their production at each rostrocaudal level was virtually completed within a 2-day period. Cholinergic interneurons were generated 1 or 2 days later than motor neurons at the same rostrocaudal level. In summary, the birthdays of all spinal cholinergic neurons studied followed the general rostrocaudal spatiotemporal gradient of spinal neurogenesis. In addition, the generation of cholinergic interneurons also followed the general ventrodorsal gradient. In contrast, however, autonomic motor neurons disobeyed the rule of a ventral-to-dorsal progression of spinal neuronal generation, thus adding another example in which autonomic motor neurons display unusual developmental patterns. PMID- 1757601 TI - Afferent and efferent projections of the glossopharyngeal-vagal nerve in the hagfish. AB - Anterograde and retrograde transport of horseradish peroxidase was used to examine the afferent and efferent projections of the glossopharyngeal-vagal nerve in the hagfish Eptatretus burgeri. Anterogradely labeled ganglion cells are scattered in the glossopharyngeal-vagal nerve trunk, in the saccular ganglion, and in the brainstem. Afferent fibers of the glossopharyngeal-vagal nerve terminate in both the vagal lobe and the fasciculus communis. Close observation showed no morphological differentiation between these two structures, indicating that they are not separate entities, but a single, continuous structure that is homologous with the nucleus and tractus solitarius of other vertebrates. The median part of this structure (the commissura infima) is displaced more rostrally than the same part of the solitary nucleus in many other vertebrates. Some of the afferent fibers invade the ventral portion of the trigeminal sensory nucleus, which receives the maxillo-mandibular nerve fibers, and terminate there. Our study showed that the hagfish has only one nucleus in the vagal motor system, i.e., the vagal motor nucleus, which contains both parasympathetic and branchiomotor neurons. The dendrites of the vagal motor neurons in the hagfish are more highly developed than those in other vertebrates. This suggests that the motor reflex arc of the glossopharyngeal-vagal nerve in hagfishes may be simpler than in other vertebrates. PMID- 1757602 TI - The size and dendritic structure of HRP-labeled gamma motoneurons in the cat spinal cord. AB - We report quantitative data obtained from 60 fully reconstructed dendritic trees belonging to eight gamma-motoneurons (gamma-MNs) and six additional gamma-MNs that were not completely reconstructed. The cells were labeled intracellularly with horseradish peroxidase (HRP). These data are compared to measurements from 79 reconstructed dendrites belonging to seven documented alpha-motoneurons (alpha MNs), supplemented by a larger sample of alpha-MNs labeled intracellularly or by retrograde transport with HRP. As expected from earlier studies, the soma dimensions and total membrane area of gamma-MNs were smaller than those of alpha MNs. Although gamma-MN dendrites were, on average, slightly but significantly longer than those of alpha-MNs, the former had, on average, smaller diameter stem dendrites, less membrane area, and less profuse branching, and they tended to branch closer to the soma and to terminate farther from the soma. These differences were evident even when subsets of dendrites with similar stem diameters were compared. Some of the anatomical distinctions suggest that gamma MNs are qualitatively as well as quantitatively different from alpha-MNs, even though the distributions of many of the morphological variables examined showed no abrupt discontinuities between the two motoneuron groups. PMID- 1757603 TI - Dermatopharmacologic investigations of halobetasol propionate in comparison with clobetasol 17-propionate. AB - Both halobetasol propionate and clobetasol 17-propionate exerted very marked antiinflammatory, antiproliferative, and vasoconstrictive effects during evaluation in a range of dermatopharmacologic models. Halobetasol propionate was distinctly more potent than clobetasol 17-propionate in the ultraviolet-induced dermatitis inhibition assay in guinea pigs and in the rat model of oxazolone induced late inflammatory reaction. Halobetasol propionate was slightly more potent than clobetasol 17-propionate in inhibiting croton oil-induced ear edema in rats and mice and in the mouse model of oxazolone-induced early inflammatory reaction. In the cotton-pellet granuloma assay in rats and the epidermal hyperplasia inhibition assay in guinea pigs, halobetasol propionate was distinctly superior to clobetasol 17-propionate. There was a trend in favor of halobetasol propionate in the cutaneous vasoconstriction assay performed in volunteers with ethanol solutions of halobetasol propionate and clobetasol 17 propionate. In a further vasoconstriction assay, performed with a 0.05% concentration of both halobetasol propionate and clobetasol 17-propionate in cream and ointment formulations, halobetasol propionate ointment yielded the highest blanching score. In a hypothalamic-pituitary-adrenal axis study in volunteers, effects of 0.05% halobetasol propionate ointment and 0.05% clobetasol 17-propionate ointment on serum cortisol levels were similar. The overall efficacy trends demonstrated in these dermatopharmacologic studies are in agreement with predictions made from corticosteroid structure and activity relationships and the results of two clinical trials comparing halobetasol propionate and clobetasol 17-propionate ointments in the treatment of plaque psoriasis. PMID- 1757604 TI - Halobetasol propionate: a trihalogenated ultrapotent topical corticosteroid. PMID- 1757605 TI - A double-blind, multicenter comparison of 0.05% halobetasol propionate ointment and 0.05% clobetasol propionate ointment in patients with chronic, localized plaque psoriasis. AB - In a double-blind, parallel-group, multicenter trial in 134 patients with severe, localized, plaque psoriasis, the success rate (described as "healed" or "marked improvement") at the end of the study was 96% in the halobetasol propionate group and 91% in the clobetasol propionate group. A significantly larger proportion of patients treated with halobetasol had no disease or mild disease after 14 days compared with those treated with clobetasol (86% versus 70%, p = 0.023). Healing within 24 days of starting treatment was noted in 69% and 56% of patients treated with halobetasol and clobetasol, respectively. Adverse effects were reported in a smaller percentage of patients treated with halobetasol propionate ointment than in those treated with clobetasol propionate ointment (7% versus 12%). Cosmetic acceptability and ease of application were recorded as "very good" in a larger percentage of patients treated with halobetasol propionate ointment than in the group treated with clobetasol propionate (90% versus 80%). PMID- 1757606 TI - A double-blind, multicenter comparison between 0.05% halobetasol propionate ointment and 0.05% betamethasone dipropionate ointment in chronic plaque psoriasis. AB - In a double-blind, parallel-group, multicenter comparative trial on 104 evaluable patients with severe, localized plaque psoriasis, 0.05% halobetasol propionate ointment demonstrated an 88.7% success rate assessed as "healed" or "marked improvement" compared with 78.5% for 0.05% betamethasone dipropionate ointment. Healing was observed within 24 days of the start of treatment in 40% and 25% of the patients who received halobetasol propionate and betamethasone dipropionate ointments, respectively. After 4 weeks' treatment, tolerability of both ointments was good. Neither skin atrophy nor systemic adverse effects were observed. Patient acceptance of halobetasol propionate ointment, based on cosmetic acceptability and ease of application, was significantly better (p = 0.02) than that of betamethasone dipropionate ointment. PMID- 1757607 TI - A comparative, multicenter, double blind trial of 0.05% halobetasol propionate ointment and 0.1% betamethasone valerate ointment in the treatment of patients with chronic, localized plaque psoriasis. AB - In a double-blind, parallel-group, multicenter comparative trial in 84 evaluable patients with severe, localized plaque psoriasis, 0.05% halobetasol propionate ointment proved significantly superior (p = 0.02) to 0.1% betamethasone valerate ointment with respect to the success rate, as indicated by ratings of "healed" or "marked improvement" (88.1% versus 64.3%). The therapeutic effect was observed within 5 days of the start of treatment in 76% and 67% of the patients treated with halobetasol propionate and betamethasone valerate ointments, respectively. Both preparations were well tolerated. Minor adverse effects at the site of application were reported in only 2% of the patients in each treatment group. Neither skin atrophy nor systemic adverse effects were observed. PMID- 1757608 TI - A double-blind, multicenter trial of 0.05% halobetasol propionate ointment and 0.05% clobetasol 17-propionate ointment in the treatment of patients with chronic, localized atopic dermatitis or lichen simplex chronicus. AB - In a double-blind, parallel-group, multicenter comparative trial in 127 evaluable patients with chronic, localized atopic dermatitis or lichen simplex chronicus, healing was reported in a higher percentage of patients treated with halobetasol propionate ointment than in those in the clobetasol propionate treatment group (65.1% versus 54.7%). The success rates (described as "healed" and "marked improvement") were practically identical in the two treatment groups (93.7% versus 92.2%). Early onset of therapeutic effect, that is, within 3 days of the start of treatment, was similar in the two treatment groups (24% versus 28%). Both preparations were well tolerated. Adverse effects were reported in 5% and 2% of the patients treated with halobetasol propionate and clobetasol propionate ointments, respectively. PMID- 1757609 TI - A double-blind, multicenter, parallel-group trial with 0.05% halobetasol propionate ointment versus 0.1% diflucortolone valerate ointment in patients with severe, chronic atopic dermatitis or lichen simplex chronicus. AB - In a double-blind, parallel-group, multicenter, comparative trial in 120 evaluable patients with chronic, localized atopic dermatitis or lichen simplex chronicus, the success rate (described as "healed" and "marked improvement") was 91.5% in patients treated with halobetasol propionate ointment and 83.6% in those in the diflucortolone valerate treatment group. Of patients treated with halobetasol propionate ointment, 40.7% reported healing within 17 days, whereas of those in the diflucortolone valerate treatment group, 32.8% reported healing within that time. Early onset of therapeutic effect, that is, within 3 days of the start of treatment, was reported in a higher percentage of patients treated with halobetasol propionate ointment than in those treated with diflucortolone valerate ointment (70% versus 59%). Adverse effects at the site of application were less frequently reported in patients belonging to the halobetasol propionate treatment group than in those treated with diflucortolone valerate ointment (3% versus 8%). PMID- 1757610 TI - Double-blind, comparative clinical trials with halobetasol propionate cream in patients with atopic dermatitis. AB - In two double-blind, parallel-group, multicenter trials, 0.05% halobetasol propionate cream was compared with 0.05% clobetasol 17-propionate cream and 0.05% betamethasone dipropionate cream in 264 patients with acute, severe exacerbations of atopic dermatitis. The efficacy of halobetasol propionate cream and betamethasone dipropionate cream was similar with regard to the success rate, as indicated by ratings of "healed" and "marked improvement" (88% versus 90%) and by an onset of therapeutic effect within 3 days of the start of treatment (40% versus 39%). The efficacy of halobetasol propionate cream and clobetasol 17 propionate cream was also similar with regard to success rates (89% versus 93%) and an onset of therapeutic effect within 3 days of the start of treatment (41% versus 38%). All three creams were well tolerated. Dryness of the skin and itching at the site of application were the reported adverse effects. Treatment was discontinued because of severe dryness of the skin in 1 of the 121 patients treated with halobetasol propionate cream and in 1 of the 59 patients treated with betamethasone dipropionate cream. PMID- 1757611 TI - Halobetasol propionate cream by day and halobetasol propionate ointment at night for the treatment of pediatric patients with chronic, localized plaque psoriasis and atopic dermatitis. AB - In a multicenter, 14-day pediatric study in 81 evaluable patients with severe, localized corticosteroid-susceptible dermatoses, the combined treatment with halobetasol propionate cream once during the day and halobetasol propionate ointment once at night produced a very satisfactory therapeutic effect. The success rates, as indicated by ratings of "healed" and "marked improvement," were 100% and 90.9% in patients with atopic dermatitis and psoriasis vulgaris, respectively. Healing was reported in 86.8% and 72.7% of patients treated for atopic dermatitis and psoriasis, respectively. Both the cream and ointment preparations were well tolerated. Adverse effects at the site of application were reported in only 3 of 81 patients. Mild skin atrophy was observed in one patient. No systemic adverse effects were observed. PMID- 1757612 TI - Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies. AB - The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757613 TI - A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis. AB - The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high potency corticosteroid preparation, was evaluated in a double-blind, vehicle controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's "effectiveness" and "overall rating." All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for "effectiveness" and "overall rating" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of "stings" or "burns" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis. PMID- 1757614 TI - A review of two controlled multicenter trials comparing 0.05% halobetasol propionate ointment to its vehicle in the treatment of chronic eczematous dermatoses. AB - The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations. PMID- 1757616 TI - Potent bactericidal activity of bovine lactoferrin hydrolysate produced by heat treatment at acidic pH. AB - A hydrolysate of bovine lactoferrin produced by heat treatment under acidic conditions had antibacterial activity at concentrations of 10 micrograms/ml in the culture medium. The optimal degree of hydrolysis for this activity was about 10%. Heat-treated lactoferrin, treated at pH 2.0 and 120 degrees C for 15 min and degree of hydrolysis of about 10%, had no Fe-binding capacity (0%) and less antigenicity (about 10(-6) than untreated lactoferrin. Heat-treated lactoferrin increased in antibacterial activity, and the activity was maintained in an Fe rich medium. After fractionation of heat-treated lactoferrin by reverse-phase HPLC, several peptide fractions were found that had strong antibacterial activity. It was suggested that lactoferrin latently contains at least one bactericidal domain that is activated upon release by limited acid hydrolysis of the protein. The bactericidal activity of the peptide fragments of lactoferrin was shown to have no relation to Fe chelation, in contrast with the antibacterial mechanism of native lactoferrin. PMID- 1757615 TI - Double-blind bilateral paired comparison of 0.05% halobetasol propionate cream and its vehicle in patients with chronic atopic dermatitis and other eczematous dermatoses. AB - Six investigators evaluated 0.05% halobetasol propionate cream and its vehicle in 111 patients with chronic atopic dermatitis and several other eczematous dermatoses. Patients applied treatment twice daily to bilateral lesions for 14 days. Investigators graded pruritus, erythema, scaling, papulation, and lichenification using 4-point severity scales on days 0, 7, and 14. On day 14 patients provided an assessment of efficacy for both treatments. Statistically significant differences favoring halobetasol propionate over the vehicle were seen for all signs and symptoms (p less than 0.001). Substantial improvements were achieved by the active treatment by day 7 (p less than 0.001). Patients assessments of efficacy were significantly higher for halobetasol cream than for vehicle (p less than 0.001). No instances of systemic effects or skin atrophy were reported and adverse experiences were limited to burning or stinging and other minor, nonspecific complaints distributed uniformly between active treatment and vehicle. These results demonstrate that 0.05% halobetasol propionate cream is highly effective in the treatment of atopic dermatitis and other eczematous dermatoses. PMID- 1757617 TI - The binding ability of alpha-lactalbumin and beta-lactoglobulin to mutagenic heterocyclic amines. AB - The binding ability of bovine milk proteins with mutagenic heterocyclic amines was investigated. Binding was determined with 2 mg of beta-lactoglobulin and 20 micrograms of heterocyclic amine in .4 ml of pH 7.4, 50 mM phosphate buffer, at 37 degrees C, in a shaker for 10 min. The unbound heterocyclic amine in protein free ultrafiltrate was analyzed by HPLC method. The binding of alpha-lactalbumin, beta-lactoglobulin A and beta-lactoglobulin B were 90.44, 81.38, and 89.18%, respectively, with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole; 37.85, 34.04, and 43.90%, respectively, with 3-amino-1-methyl-5H-pyrido[4,3-b]indole; and 49.11, 43.25, and 57.44%, respectively, with 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole. Binding of beta-lactoglobulin and alpha-lactalbumin to 3-amino-1,4 dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido [4,3-b]-indole was higher at pH conditions above 7.4, and binding was lost at pH less than 5.5. Maximum binding of both proteins to 2-amino-6-methyl-dipyrido[1,2-a:3',2' d]imidazole was at pH 7.4, and binding was inhibited at pH conditions above 8.5 and less than 6.5. PMID- 1757618 TI - Suppression of milk production during endotoxin-induced mastitis. AB - Healthy, midlactation cows were given intramammary infusions of 10 micrograms of endotoxin in two homolateral quarters. Productive, inflammatory, and systemic responses were studied to investigate the pathophysiological effects of mastitis on lactational performance. Endotoxin suppressed milk yield in all quarters of treated cows. A more severe and prolonged suppression occurred in infused quarters compared with uninfused quarters. The fat percentage of milk from all quarters was increased with a greater increase occurring in infused quarters. The protein composition of milk was elevated, and the lactose concentration was depressed in infused quarters. Mammary inflammation--as measured by milk SCC, NAGase, serum albumin, and lactoferrin--was limited to infused quarters. Changes in milk NAGase closely paralleled changes in milk SCC. Daily feed intake was unaffected, and serum glucose levels did not decline following infusion. The lactose concentration of urine increased rapidly after infusion. Reduction in milk yield in all quarters, but varying changes in milk composition in infused versus uninfused quarters suggest that mastitic hypogalactia is mediated by multiple pathophysiological events and is not solely due to inflammatory damage to the mammary epithelium. Part of the reduced lactational performance may result from escape of milk components from the udder into the circulation. PMID- 1757619 TI - Effects of supplemental vitamin A or beta-carotene during the dry period and early lactation on udder health. AB - Effects of vitamin A or beta-carotene supplementation during the dry period and early lactation on the frequency of new intramammary infection and clinical mastitis and on SCC and milk yield were examined. Eighty-two Holstein cows were randomly assigned to one of three groups: 1) 50,000 IU/d of vitamin A per cow (approximately equivalent to 1978 NRC recommended daily intake for dairy cows); 2) 170,000 IU/d of vitamin A per cow; or 3) 50,000 IU/d of vitamin A plus 300 mg of beta-carotene per cow. Cows were supplemented during the 2 wk before drying off, throughout the dry period, and for the first 6 wk of lactation. Concentrations of serum vitamin A did not differ among treatment groups but tended to decrease for all treatment groups from 14 d before drying off to calving. After calving, serum vitamin A tended to increase in all groups through wk 6 of lactation. Serum beta-carotene tended to be higher in beta-carotene supplemented cows at dry-off, in the early dry period, and again during lactation. Serum beta-carotene decreased sharply in all groups during the prepartum period. The frequency of clinical mastitis and of new intramammary infection during the dry period, near parturition, and for the first 6 wk of lactation did not differ among treatment groups. The percentage of quarters newly infected over the entire trial was 26.8 in the control, 25.0 in the high vitamin A, and 30.6 in the beta-carotene group. Pathogens isolated most frequently were coagulase-negative staphylococci, streptococci other than Streptococcus agalactiae, and coliforms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757620 TI - Variation in milk somatic cells of heifers at first calving. AB - To evaluate variation in milk somatic cells, 24 primiparous cows (paired by calving date) were sampled during the first 75 d of lactation. Milk somatic cell counts were lowest at 9 to 10 wk. For differential cell counts in milk, only percentage of macrophages changed significantly during first 75 d (33% at 1 wk, 25% at 6 wk, and 34% at 11 wk). Epithelial cells were identified and ranged from 11 to 20% of total. For milk somatic cell count, variation between cows within pairs sampled contemporaneously was small (3 to 24%). However, variation between cows was much greater for the differential cell counts (46% of total for lymphocytes and 34% for epithelial cells). Of 1021 quarter foremilk samples, 26 were positive for major pathogens, but 326 were positive for various species. Prevalence of bacteria was significantly higher during first 10 d after calving. Rear quarters had significantly higher bacterial presence: 47% for left rear versus 21% for left front and 37% for right rear versus 24% for right front. Total milk somatic cell count after first calving appears to depend primarily on differences in temporary factors and is not a stable characteristic of individual cows. Proportions of the different somatic cell types in milk may vary consistently by cow in early first lactation. PMID- 1757621 TI - Patterns of nutrient uptake by the mammary glands of lactating dairy cows. AB - Twenty-one multiparous lactating dairy cows with previous 305-d milk production records varying from 5900 to 13,600 kg were used to examine patterns of nutrient uptake by the mammary glands. On d 71 and continuing until d 126 of lactation, animals were injected daily with 40 mg of sometribove (bST group) or bicarbonate buffer (control group). Arterial and venous blood plasma samples were collected over a 12-h period on d 35, 70, 105, and 126 of lactation. Regression equations developed to evaluate linear effects of plasma arterial concentrations on net arterial-venous difference across the mammary glands demonstrated that, for acetate, NEFA, and D-beta-hydroxybutyrate, plasma arterial concentration accounted for over 50% of variation in uptake by the mammary glands. Additionally, a sigmoidal equation fitted the relationship between D-beta hydroxybutyrate plasma arterial concentration and mammary gland uptake (r2 = .70). Triacylglyceride concentration was less effective in predicting uptake (r2 = .25). Administration of bST did not alter patterns of nutrient uptake, but a fourfold increase in NEFA uptake was predicted for bST-treated cows from this study, using NEFA concentrations from the literature. These observations indicate that plasma concentrations of acetate, NEFA, D-beta-hydroxybutyrate, and triacylglyceride are major determinants of uptake by the mammary glands. Factors other than plasma concentration, such as mammary gland biosynthetic capacity, availability of other nutrients, and blood flow, determine uptakes of glucose, lactate, and total and free cholesterol (r2 less than or equal to .03). PMID- 1757622 TI - Relationship of early lactation and bovine somatotropin on nutrient uptake by cow mammary glands. AB - Twenty-one multiparous lactating dairy cows with previous 305-d milk production records varying from 5900 to 13,600 kg were used to investigate effects of bST administration and stage of lactation on nutrient plasma arterial concentrations and arterial-venous differences across the mammary glands (uptake). On d 71 and continuing until d 126 of lactation, cows were injected with 40 mg of sometribove (bST group) or bicarbonate buffer (placebo group). Arterial and venous blood plasma samples were collected over a 12-h period on d 35, 70, 105, and 126 of lactation. Plasma concentration of glucose was 7% higher in midlactation compared with early lactation cows. Plasma concentration of acetate decreased from 2.11 to 1.87 mM in placebo versus bST-treated cows. Plasma arterial concentration and uptake of D-beta-hydroxybutyrate were .52 and .18 mM higher, respectively, in early versus midlactation cows. Concentration and uptake of NEFA were elevated in both early lactation and bST-treated cows. Triacylglyceride concentrations were 24 and 19% lower in early lactation and bST-treated cows compared with midlactation cows receiving placebo. Likewise, uptake of triacylglyceride was reduced in early lactation and with bST treatment compared with midlactation. The mediation of nutrient delivery and uptake by the mammary gland appears to be markedly similar between early lactation and bST-treated cows, suggesting a similarity between these physiological states and the homeostatic and homeorhetic mechanisms regulating nutrient partitioning in the lactating dairy cow. In early compared with midlactation cows receiving placebo, uptakes of D-beta hydroxybutyrate and NEFA were reduced, and triacylglyceride uptake increased. PMID- 1757623 TI - Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 1. Production response. AB - This study evaluated the effect of sometribove (zinc methionyl bST) in a sustained-release formulation administered to lactating cows at concentrations up to 3.0 g every 14 d over two lactations. Eighty-two lactating Holstein cows in their first, second, or third lactation were assigned to the study. Cows received .6, 1.8, or 3.0 g of bST in one, three, or five intramuscular injections of a unit dose (.6 g) every 2 wk. Controls received five injections of the vehicle (equivalent volume to the 3.0-g treatment) every 2 wk. Injections were administered from 60 +/- 3 d postpartum until dry-off or necropsy. Thirty-eight animals were continued on treatment for a second consecutive lactation. During the 1st yr of treatment, bST increased mean 3.5% FCM by 7.2, 9.4, and 8.4 kg/d over control production (21.1 kg/d). During the 2nd yr, milk response to .6, 1.8, and 3.0 g of bST averaged 10.6, 3.6, and 4.9 kg/d over controls (24.8 kg/d). The incidence of clinical mastitis increased in the 3.0-g group relative to controls during the 2nd yr. Thus, salable FCM averaged 8.1, 9.1, and 6.2 kg/d above controls (yr 1) and 12.1, 4.7, and -2.8 kg/d (yr 2) for the .6-, 1.8-, and 3.0-g groups. Salable FCM was unaffected by mastitis at a proposed commercial dose (.6 g). Milk fat, protein, lactose, calcium, phosphorus, zinc, magnesium, and ash concentrations were unaffected by bST treatment. Calculated energy, calcium, phosphorus, and protein balances also were unaffected except for early decreases of up to 5 Mcal/d, and 40, 20, and 600 g/d, respectively, until feed intake increased. Milk serum bST concentrations greater than the assay limit of sensitivity (1 ng/ml) were routinely measurable only at doses of 1.8 and 3.0 g. Results confirmed that bST concentrations in milk serum are exceedingly small. Overall, supraphysiological doses of sometribove increased milk production with little effect on composition. No toxic effects of bST were observed. PMID- 1757624 TI - Effects of scrotal insulation on viability characteristics of cryopreserved bovine semen. AB - The effect of a 48-h scrotal insulation on spermatozoal viability (motility and acrosomal integrity), before and after semen cryopreservation, was studied in six young Holstein bulls whose semen was collected twice in succession at 3-d intervals. Motility and acrosomal integrity were measured before and after incubation of semen at 37 degrees C for 3 h. For assessment of results, collection days were grouped: period 1 (control) = d -6, -3, and 0, where d 0 = initiation of scrotal insulation after semen collection; period 2 = d 3, 6, and 9 (sperm presumed in the epididymis or rete testis during scrotal insulation); period 3 = d 12, 15, ... 39 (sperm presumed in spermatogenesis during scrotal insulation). Semen was cryopreserved each collection day until morphologically abnormal cells exceeded 50% of the ejaculate (d 12 to 21). Semen viability before and after freezing was lower in period 3 than in period 1 (P less than .05). These differences coincided with the appearance in period 3 of abnormal sperm morphology and depressed undiluted semen motility, which began on d 12 (P less than .01). Semen collected during period 2 that was extended but unfrozen did not differ from that collected during period 1 in morphology or viability. However, for frozen semen, period 2 was significantly poorer than period 1 for both viability measurements, but only after incubation for 3 h at 37 degrees C postthaw (P less than .05). We conclude that epididymal sperm are adversely affected by elevated testicular temperatures, as noted by their decreased ability to maintain motility and acrosomal integrity following cryopreservation. PMID- 1757625 TI - Pregnancy rates of Holstein cows after postinsemination treatment with a progesterone-releasing intravaginal device. AB - Our objective was to determine whether pregnancy rates following first services would be improved by supplementing lactating dairy cows with exogenous progesterone via a progesterone-releasing intravaginal device. Estrus was induced in cows with PGF2 alpha (3-wk clusters of cows ranging from 42 to 63 d postpartum) following a positive milk test for high progesterone. Cows were inseminated at estrus (d 0), and progesterone was administered via the device from d 5 to 13 or d 13 to 21 following estrus; untreated inseminated cows served as controls. Blood was collected from each cow on d 5, 13, and 21 to determine concentrations of progesterone in blood serum. A fourth group of inseminated cows not receiving PGF2 alpha served as an additional untreated, and nonbled, control group. Pregnancy rates at first services, which were followed by insertion of the device, were unaffected by treatments. Concentrations of progesterone in serum were higher in pregnant than nonpregnant cows on d 13 but similar in cows regardless of postinsemination treatment. By d 21, when concentrations of progesterone remained consistently higher as a result of pregnancy, cows given progesterone from d 13 to 21 had higher progesterone in their blood serum, regardless of pregnancy status, than cows receiving progesterone from d 5 to 13. Only serum progesterone in nonpregnant controls on d 21 was less than that of nonpregnant cows given progesterone on d 13 to 21. Pregnancy rates of cows returning to estrus 21 to 27 d after their first service tended to be higher (60 versus 39%) in those cows previously treated with exogenous progesterone than in controls. Furthermore, the proportion returning to estrus 17 to 27 d after first service was reduced in cows previously supplemented with exogenous progesterone (27 versus 49%). Days from calving to conception were 19 d fewer in cows previously treated with progesterone than controls, because average intervals to first service were decreased by 13 d relative to controls. We conclude that supplementing cows with progesterone after insemination initially failed to improve pregnancy rates but appeared to increase pregnancy rate at the subsequent service. PMID- 1757626 TI - Activity monitoring and an enzyme immunoassay for milk progesterone to aid in the detection of estrus. AB - The accuracy and efficiency of estrus detection using an electronic activity monitor tag in conjunction with an enzyme immunoassay for milk progesterone were studied during 55 observed estrous periods in 37 cows. At approximately 30 d postpartum, cows were equipped with an activity tag and visually observed for estrus, an activity tag with a flashing light-emitting diode, or both twice daily. Milk progesterone concentrations were determined from cows observed in estrus or with an activated tag. Mean daily activity was greater on the day of estrus than during any of the 3 d preceding or 3 d following estrus. Functioning activity tags correctly identified 55% of all visually observed estrous periods that coincided with low milk progesterone levels. The overall accuracy of a flag by the tag for identifying true estrus was 21%. The enzyme immunoassay for milk progesterone was in agreement with 98% of all visually observed estrous periods and false flags committed by the tags. Although the activity tags detected some cows in estrus, a more durable and reliable tag must be developed before it is of practical value to dairy producers. PMID- 1757627 TI - Addition of chloride to a prepartal diet high in cations increases 1,25 dihydroxyvitamin D response to hypocalcemia preventing milk fever. AB - In this study, we present evidence that cows fed highly cationic diets are less responsive to parathyroid hormone than those fed a highly anionic diet. Forty seven Jersey cows (55 mo of age) were fed an alfalfa haylage-based diet supplemented with either anions (Cl-) or cations (Na+). Cows fed the high cationic diet suffered significantly more cases of milk fever (6 out of 23) than those fed the high anionic diet (1 out of 24). Concentrations of Ca at parturition and the first 2 d of lactation were significantly higher in cows fed the anionic diet. Secretion of parathyroid hormone in response to developing hypocalcemia was similar in cows fed either diet. Plasma hydroxyproline concentration (an index of bone Ca resorption activity) was greater in cows fed the anionic diet, suggesting better utilization of bone Ca. Plasma 1,25 dihydroxyvitamin D concentration was correlated inversely with plasma Ca and related directly to plasma parathyroid hormone in both groups of cows. However, the magnitude of the response (the amount of 1,25-dihydroxyvitamin D produced per unit increase in parathyroid hormone) was reduced greatly in cows fed the high cation diet. Because parathyroid hormone regulates both bone Ca resorption and renal 1,25-dihydroxyvitamin D production, these data suggest that prepartal diets high in cations decrease the ability of bone and renal tissues to respond to parathyroid hormone. Addition of anions to prepartal diets can reduce the excess cation balance of diets, increasing tissue response to parathyroid hormone and enabling the cow to better adapt to the Ca demands of lactation. PMID- 1757628 TI - Effects of varying dietary undegradable protein on dry matter intake, growth, and carcass composition of Holstein calves. AB - The objective was to study the effect of feeding diets varying in rumen undegradable protein on DMI, growth, feed efficiency, and carcass composition in Holstein calves from birth to 25 wk of age. Sixty Holstein calves were assigned in a randomized complete block design to one of three dietary treatment groups that differed in rumen undegradable protein as a percentage of total protein. Protein undegradabilities of the TMR fed for ad libitum intake for period 1 (wk 1 to 12 of age) were 33, 37, and 46% and for period 2 (wk 14 to 25 of age) were 30, 34, and 38%. Intake was not different among diets during period 1. During period 2, animals fed the highest and lowest levels of undegradable protein diet consumed less DM, and those animals on the highest undegradable diet had the least amount of crude protein intake. Feed efficiency was increased with increasing rumen undegradable protein for period 2. Carcass composition was not affected by dietary treatment for either 9-10-11 rib section or the half carcass. Prediction equations for carcass protein and fat were calculated for 25-wk Holstein calves using urea space and live weight. These results indicate that the amount of undegradable intake protein currently recommended for growing dairy replacements may not be justified when intake is ad libitum. In the present study, urea space was not found to be beneficial over live weight for predicting carcass protein and fat in intact male or female Holstein calves. PMID- 1757629 TI - Lactational response of dairy cows to increased dietary crude protein with added fat. AB - Thirty-six Holstein cows were assigned to one of three diets containing soybean meal (16% CP), added fat from extruded soybeans (16% CP), and added fat and protein from extruded soybeans plus soybean meal (18% CP) to determine whether feeding additional protein would prevent the depression in milk protein percentages usually experienced when cows are fed additional fat. Total mixed diets containing 25% corn silage, 25% alfalfa hay, and 50% of respective concentrate mixtures were fed individually wk 4 through 16 postpartum; pretreatment (wk 3 postpartum), milk production, and composition data were used as covariates. Milk production (33.0, 35.8, and 34.2 kg/d) was higher for cows fed added fat. Milk protein (2.92, 2.88, and 2.83%) and casein (2.16, 2.13, and 2.09%) tended to decrease for cows fed added fat and did not increase with higher dietary protein. Dry matter intakes (20.9, 20.7, and 19.8 kg/d) and BW were similar for all diets. Supplementing additional CP to a diet containing added fat did not prevent depression in milk protein percentage. PMID- 1757630 TI - Effects of sometribove on performance, carcass composition, and chemical blood characteristics of dairy calves. AB - Ten intact male Holstein calves averaging 75 kg of BW and 59 d of age were used to study the effects of daily injections of 0 (control) or 10 mg of sometribove (recombinant methionyl bST) for 6 wk on performance, health, carcass composition, N metabolism, chemical blood characteristics, and hormone profiles. Average daily gain, feed intake, feed:gain ratio, and height at withers, hip, and hock were not influenced by bST. Carcasses from bST-treated calves contained 5% more protein and 36% less lipid than controls. Circulating concentrations of Ca, P, glucose, urea N, alkaline phosphatase, creatine phosphokinase, insulin-like growth factor I, and insulin were not affected by bST. Packed cell volume was decreased about 7% (29.9 vs. 32.4%) in the bST calves. Hormone injection did not adversely affect health of the calves as measured by body temperature and by pulse and respiration rates. The most profound effects of sometribove were a reduction in carcass lipid and an increase in body proteins. These effects may be of some practical importance when leanness of carcass is desirable. PMID- 1757631 TI - Effect of temperature on colostrometer readings for estimation of immunoglobulin concentration in bovine colostrum. AB - Effect of temperature on colostrometer readings for estimation of immunoglobulin concentration in bovine colostrum was investigated. Twenty-five colostrum samples were collected within 24 h postpartum from Holstein cows. Immunoglobulin concentration of colostrum was measured using a colostrometer through 5 degrees C increments from 0 to 40 degrees C. Two technicians measured independently a total of 225 samples. The agreement between technicians' readings was high (r = .98); thus, readings were averaged and used in regression analysis. A final regression model explained 92.5% of the total variation: corrected reading at 20 degrees C = uncorrected reading - 13.2 + .8 x temperature (degrees C). The regression equation was used to develop a conversion chart for practical field use. PMID- 1757632 TI - Effect of excess dietary manganese on lipid composition of calf blood plasma, heart, and liver. AB - Preruminant calves were fed milk replacer containing control (40 ppm) or two high concentrations (200 and 1000 ppm) of Mn to assess the effect of excessive Mn intakes on plasma, heart, and liver lipids. The two higher Mn intakes had no effect on lipid classes in liver and heart, except for elevated triglycerides in liver and lower sphingomyelin in heart (for 1000 ppm of Mn). At 1000 ppm of Mn intake, but not at 200 ppm, marked increases occurred in plasma total lipids, phosphatidylcholine, cholesterol, cholesterol esters, sphingomyelin, and triglycerides. The highest intake altered the essential fatty acid composition of liver phosphatidylcholine. Linoleic and linolenic acids were increased, but arachidonic and eicosapentaenoic acids were decreased, suggesting that very high excess of Mn interfered with hepatic desaturation and elongation of the essential fatty acids. Thus, high Mn intake (200 ppm) caused relatively few tissue lipid changes, whereas very high intake (1000 ppm) markedly increased plasma lipid classes and apparently interfered with essential fatty acid metabolism in liver. PMID- 1757633 TI - Evaluation of starter diet crude protein level and feeding regimen for calves weaned at 26 days of age. AB - The objectives of this study were to evaluate two levels of CP in starter diets offered to calves weaned on d 26 and to compare postweaning intake of starter diets and performance of calves weaned at 26 or 42 d. Forty Holstein calves were housed in individual outdoor hutches and assigned to one of four treatments. Treatments consisted of weaning on d 26 after offering a 20% CP starter diet from d 1, or d 21, or after offering a 25% CP starter diet from d 21, or weaning on d 42 after offering a 20% CP starter diet from d 1 (control). Between d 42 and 84, calves were commingled in outdoor group pens. On d 42, BW of control calves was heavier than that of early weaned calves. On d 84, BW did not differ among treatments. Consumption of starter diet was not affected by the age at which it was first offered. Weaned calves consumed more starter diet than controls from d 29 to 42. Postweaning performance was not affected by increasing CP in the starter diet. Weaning treatment did not affect the incidence of scours. Comparison of CP intakes with current NRC recommendations suggests that CP requirements for young milk-fed calves are adequate. PMID- 1757634 TI - Suppressing immature house and stable flies in outdoor calf hutches with sand, gravel, and sawdust bedding. AB - Sand, gravel, sawdust, and pine shavings were used as bedding in outdoor calf hutches and compared with straw relative to the density of immature (maggot) house flies, Musca domestica, and stable flies, Stomoxys calcitrans. In 6-wk field trials, average densities of house and stable fly maggots in concrete mix sand ranged from only .3 to 1.6 and 0 to .1 maggots/L, respectively; pea size gravel bedding also strongly suppressed densities from less than .1 to .3 and less than .1 to .1 maggots/L, respectively. These densities represent reductions of 76 to greater than 99% relative to straw bedding, but both sand and gravel compacted and became soiled with calf feces, which resulted in unacceptable bedding sanitation and foul odors. Densities of house and stable fly maggots in pine shavings did not differ from those in straw bedding. Nevertheless, in sawdust bedding, maggot density was limited to averages of 1.4 to 8.3 house and 9.8 to 11.8 stable fly maggots/L; this represented reductions of 45 to 91% relative to straw. In a follow-up trial, house and stable fly maggot densities in sawdust averaged 11.3 and 43.9 maggots/L, respectively, reductions of 77 and 46%. These findings suggest that bedding calf hutches with sawdust during warm weather can be useful as an ecologically sound approach to controlling muscoid fly populations on dairy farms. PMID- 1757635 TI - Effects of sire fertility and daughter stayability on profitability of sire selection. AB - Holstein sires (n = 340) with milk, milk fat, semen unit fertility, daughter stayability evaluations, and semen price for 1986 were studied. Effects of variation in sire fertility and daughter stayability on profitability of sire selection using the net present value criterion were estimated. The model estimated expected profit from a cow bred to pregnancy from future production and from cattle disposal and replacement after discounting costs and returns to the time of insemination. Effects of semen sexing and semen unit dilution on profitability to determine optimal breeding strategies for dairy herds were examined. Sire profitability increased with herd average conception rate and sire selection intensity. Daughter stayability had a greater impact on profitability than semen unit fertility when profit maximization was computed under the criterion of breeding a cow to pregnancy. Genetic progress for production was compromised when selecting to maximize profit. Dilution of semen units seems profitable only when semen availability is limited for high demand sires. The use of sexed female semen may only be appropriate when it can generate additional income from the sale of surplus heifers. PMID- 1757636 TI - Using embryo sexing within closed mixed multiple ovulation and embryo transfer schemes for selection on dairy cattle. AB - Two types of multiple ovulation and embryo transfer schemes that included bull progeny testing were compared. In the juvenile schemes, embryos were collected at 16 to 18 mo of age without sexing, whereas, in the adult schemes, donors were chosen based on their first lactation record, and their embryos were systematically sexed. With the latter schemes, natural calves obtained at the first two calvings could compete with embryo transfer calves to be replacements. The optimal structure of this scheme was derived algebraically for the same number of transferred embryos as in the juvenile schemes. Predicted asymptotic annual genetic gains, after stabilization of genetic parameters taking into account the Bulmer effect, were found to be slightly in favor of the adult schemes for a given set of parameters (overall number of transferred embryos, number of embryos per collection, and embryo survival rate). In the adult schemes, the nucleus sizes were much larger than in the juvenile schemes, which allowed a higher selection differential on male paths, thus compensating for the longer generation interval. Asymptotic rate of genetic gain for Monte Carlo simulations were about 10 and 7% lower for juvenile and adult schemes, respectively, but still higher (20%) than the predicted value for the corresponding conventional scheme. Consequently, adult schemes with embryo sexing can be an efficient alternative to juvenile schemes without embryo sexing. PMID- 1757637 TI - Clinical ketosis: phenotypic and genetic correlations between occurrences and with milk yield. AB - The repeatability and heritability of ketosis were estimated using data from 28,277 Finnish Ayrshire cows. A four-trait linear model including community-year, calving age and month, genetic group, and random sire effects was used to describe first and second lactation milk yields and veterinary diagnoses of ketosis. Variance components were estimated using REML. The disease traits were also analyzed with a categorical model including the same effects except that community and year were separate factors. Variance components were estimated with marginal maximum likelihood. Genetic relationships between 339 sires analyzed were included in models. The phenotypic correlation between the first and second lactation was defined as a repeatability of trait. The lactational incidence risk of ketosis was .05 in both the first and the second lactation. Average milk production was 4956 and 5547 kg in the first and second lactations, respectively. Estimates of heritabilities were .09 and .07 for ketosis and .23 and .19 for milk in the first and second lactations, respectively. Genetic correlations between first and second lactation recordings were .64 for ketosis and .93 for milk. Repeatabilities between subsequent lactations were .36 (.13 in linear analysis) for ketosis and .68 for milk. In the first lactation, genetic relationship between milk yield and ketosis was unfavorable, but in the second lactation ketosis and milk yield were genetically and phenotypically unrelated. PMID- 1757638 TI - Sire selection decisions and farm profitability relationships for Ontario dairy farmers. AB - The relationship between the relative emphasis of type and production in the sire selection decision and net farm income per cow are examined for a sample of Ontario dairy farmers. A significant positive correlation between farm profits and the genetic indices for type and production traits of selected bulls exists, but the direction of causality cannot be determined. Net farm income per cow was found to have a significant inverse association with the relative weighting between type and production in the average sire selected. In contrast, the emphasis on type relative to production was found to increase with an increase in milk yield and herd size. The results of this study show that there may be benefits to collecting the breeding, production, and economic information of selected herds. The information gathered over time would be useful for determining what factors influence breeding decisions and for determining the causality in those relationships. PMID- 1757639 TI - Potential for enhancing the nutritional properties of milk fat. AB - Milk fat has been identified as a hypercholesterolemic fat because it contains cholesterol and is primarily saturated. However, different types of dietary saturated fats do not have equivalent effects on plasma cholesterol levels relevant to ingestion of polyunsaturated fats. Research suggests that the hypercholesterolemic effect of saturated fats in human diets is largely due to 12, 14, and 16 carbon chain length fatty acids. Evidence also suggests that stearic acid (C18:0) is as effective as oleic acid (C18:ln-9) in lowering plasma cholesterol levels when either replaces palmitic acid (C16:0) in the diet of men. Milk fat has a unique fatty acid profile with approximately 10% short- and medium chain length saturated fatty acids (less than 12 carbons) and 35% of total fatty acids from stearic and oleic acids. The contribution of milk products to fat and cholesterol intake in the typical American diet is less than that provided by other animal products. This paper will review the recommendations of the National Cholesterol Education Program, the effects of milk fat ingestion on blood cholesterol, and the rationale and feasibility of three approaches to modifying the lipid composition of milk fat. PMID- 1757640 TI - Enzymes and factors controlling vitamin D metabolism and action in normal and milk fever cows. AB - In milk fever (parturient paresis), calcium homeostatic mechanisms, regulated by parathyroid hormone and 1,25-dihydroxyvitamin D, fail to maintain normal blood calcium concentrations, resulting in severe hypocalcemia. The precise nature of the endocrine defect is unknown. Secretion of parathyroid hormone and production of 1,25-dihydroxyvitamin D is similar in most cows with milk fever or without. However, there are some cows that fail to produce adequate 1,25-dihydroxyvitamin D at the onset of lactation. These tend to be cows that will suffer prolonged hypocalcemia and relapse after treatment. Assuming that most cows produce adequate amounts of both hormones, the next logical cause of milk fever might be a failure of tissues to respond to calcium-regulating hormones. Older cows are more likely to develop milk fever than younger ones. We have found that tissue 1,25-dihydroxyvitamin D receptor concentrations decline with age, leaving the tissues less able to respond to 1,25-dihydroxyvitamin D. We also have found that tissue 1,25-dihydroxyvitamin D receptor concentrations increase during pregnancy and lactation in the cow. Intestinal 1,25-dihydroxyvitamin D receptor concentration does not appear to be different in cows with or without milk fever in cows of similar ages. However, intestinal 1,25-dihydroxyvitamin D receptor numbers decrease precipitously at parturition, which may in part be responsible for the development of hypocalcemia in dairy cattle. PMID- 1757641 TI - C. R. Henderson, the statistician; and his contributions to variance components estimation. AB - C. R. Henderson's 1953 Biometrics paper "Estimation of Variance and Covariance Components" is an outstanding landmark in the discipline of statistics. It sets out the very first ideas of how to estimate variance components from unbalanced (unequal subclass numbers) data in situations more complicated than the one-way classification (completely randomized design). As such it had three important, long-lasting impacts. First, it provided methods for actually using unbalanced data, even in large quantity, for estimating variance components. And this has played a tremendous role in population genetics and in animal breeding where the use of estimated variance components is vital to the application of selection theory and selection index techniques. Second, that 1953 paper stimulated numerous statisticians to become interested in random effects, mixed models, and variance components estimation, with such statistical greats as H. O. Hartley and C. R. Rao making contributions in the late 1960s and early 1970s. By then, improved methods of estimating variance components from unbalanced data had been developed, namely maximum likelihood (ML) and restricted maximum likelihood (REML). Once computing power had expanded to the point where these methods became feasible, Henderson made notable contributions to these methods, allied to his two great interests: animal breeding and feasible computing procedures. For both of these, his mixed model equations were a salient feature. Third, these methods reached a wide audience of geneticists and statisticians. PMID- 1757642 TI - C. R. Henderson: contributions to the dairy industry. AB - Through C. R. Henderson's position and the application of his knowledge, he had a major influence on genetic improvement in dairy cattle beginning in the 1950s. He developed herdmate comparisons in the United States. The first extensive program using pedigree selection and progeny testing of sires for use in AI was because of his suggestion. This program established the direction of dairy cattle improvement that still continues. He developed BLUP and discovered how to write the inverse of an additive genetic relationship matrix, A-1, without inverting the matrix. These accomplishments had a major impact on evaluation methods of dairy cattle and other livestock species. Use of BLUP and A-1 are standards for evaluation of breeding values all over the world. His pioneering work in estimation of components of variance and analyses of unbalanced data were also of primary importance for animal evaluation and many other applications. Henderson made a major contribution to mankind. PMID- 1757643 TI - C. R. Henderson: contributions to predicting genetic merit. AB - The contributions of C. R. Henderson to the genetic evaluation of livestock have been widely accepted, utilized, and enhanced by animal breeders and statisticians. Not well known are the possible alternatives to BLUP that have been suggested by Henderson, such as biased predictors and Bayesian methodology to incorporate prior information. A search for rapid methods of inverting dominance and additive by additive genetic relationship matrices has taken place since Henderson first described his method for computing the inverse of the additive genetic relationship matrix. Accounting for inbreeding and selected base populations continues to be a problem. There is a need to derive accurate descriptions of selection processes and the appropriate selection model in order to solve the problems of cow culling, nonrandom association of sires with herd year-seasons, and preferential treatment. Henderson solved many animal breeding problems and left hints for solving others, but there are still many difficult problems to be tackled that will have to be resolved without the availability of his generous advice. PMID- 1757644 TI - C. R. Henderson: the unfinished legacy. AB - Ideas and methods developed by Henderson have been applied widely to BLUP of additive genetic merit of animals and estimation of components of variance. However, a number of other contributions of Henderson to theory and application of animal breeding and statistics have not been as fully examined and exploited. Some of these contributions are complete in their own right and others lay the groundwork to help resolve remaining problems. Henderson had insight and made contributions to the areas of analysis of line and breed cross data, hypothesis testing under mixed linear models, prediction of breeding values with unknown variances, and selection models. The general flexibility of Henderson's mixed model methods to quantify a large variety of biological effects is also illustrated and discussed in light of new technologies in genetics and biology. PMID- 1757645 TI - C. R. Henderson: farm boy, athlete, and scientist. AB - Charles R. Henderson was proud to be a product of a farm in Page County, Iowa. He was a one man track team in Coin, Iowa, and a brilliant student. He became a world class competitor in track at Iowa State College and, at the same time, compiled a top academic record. His early experiences set the stage for the exceptional contributions of his animal breeding career, which did not begin until he was nearly 40 yr of age, but which spanned 40 yr when he was the acknowledged leader in development of statistical methodology applied to animal breeding. His career goals were to find the best possible ways to analyze data and to provide the best genetic evaluations to the livestock industry. If the best could not be done because of computational limitations, then he would pragmatically work to find the best way that was possible. Only his interest in Cornell hockey overshadowed his enjoyment in listening to classical music. He was an avid sports fan, especially for the St. Louis Cardinals or any midwestern team against the New York Yankees. Midwestern trips during the weeks when the Drake Relays were held were as often as possible. Henderson's acknowledged scientific hero was Jay L. Lush, with whom he studied during his Ph.D. program at Iowa State College and with whom he shared similar talents and the intuition that made both of them leaders in the field of animal breeding. PMID- 1757646 TI - Rapid skin edge elevation using the OCT compound droplet technique to obtain horizontal microsections in Mohs micrographic surgery. AB - We describe a technique to quickly raise the skin edges when mounting flat tissue specimens on cryostat discs used in Mohs micrographic surgery. The technique consists of placing a drop of OCT compound on the superficial surface of the tissue before the specimen is mounted bottom-side-up on the cryostat object disc. When the Mohs tissue layer is transferred to the disc, the droplet spreads out underneath the tissue to support the bottom and to prevent the skin edges from dropping below the horizontal plane of the tissue. This technique assures that the skin edge and bottom surface of the tissue are on the same plane so that a complete section of the undersurface of the flat specimen is taken when the tissue is cut with the microtome. The technique is relatively simple to perform, requires no special instrumentation, and provides consistent microsections with complete skin edge. PMID- 1757647 TI - Chondrodermatitis nodularis chronica helicis. Successful treatment with the carbon dioxide laser. AB - Chondrodermatitis nodularis chronica helicis is a painful, persistent, or recurrent inflammatory lesion involving the cartilage and skin of the external ear. These lesions are resistant to many therapeutic modalities and often recur even after surgical excision. The CO2 laser was used to vaporize the cutaneous nodules and involved cartilage. The wounds were allowed to heal with only minimal care using hydrogen peroxide cleansing and applications of topical antibiotic ointment. Twelve lesions have been treated with no recurrences after 2 to 15 months. There have been no complications or infections following laser surgery. The pain from these lesions is gone immediately following laser surgery. Healing with excellent cosmetic results is complete usually within 3 to 4 weeks. PMID- 1757648 TI - Mapping and orienting tissue during Mohs micrographic surgery. An alternate approach. AB - An alternate method for mapping and orienting tissue during Mohs micrographic surgery is described. This quick and simple technique eliminates the application of indelible dyes to the tissue margins. PMID- 1757649 TI - The treatment of benign sebaceous hyperplasia with the topical application of bichloracetic acid. AB - Sebaceous hyperplasia is a benign lesion that occurs commonly on the face of older individuals. A variety of treatment options have been described, including oral isotretinoin, electrodesiccation, CO2 laser surgery, cryosurgery, and shave excision with curettage. Problems have been noted with these approaches. These techniques are more complex, less effective, require more time, or are more likely to scar than the procedure we describe. The treatment of sebaceous hyperplasia with bichloracetic acid is described with results presented after treatment of our first 20 patients. PMID- 1757650 TI - Regional anesthesia of the hand for dermatologic surgery. AB - The basic principles of regional and local anesthesia of the hand are reviewed, and safe and effective methods for outpatient dermatologic procedures and three representative cases are discussed with respect to anatomy, local anesthetic agents, and techniques. Block techniques are preferred to local infiltration because they provide complete and long-lasting anesthesia more comfortably. PMID- 1757651 TI - Unusual auricular complications in cutaneous oncology. AB - The anatomic complexity of the pinna predisposes that structure to a variety of unique, site specific postoperative complications following management of skin cancer. We describe four unusual auricular complications: 1) radiochondronecrosis; 2) autonecrosis of skin during second intention healing; 3) hearing loss secondary to tragal retraction over the external auditory canal; and 4) extension of tumor through fenestrated cartilage. Well-known postoperative auricular complications are reviewed and anticipation and recognition of these unusual complications are emphasized. PMID- 1757652 TI - The surgical management of chondrodermatitis nodularis chronica helicis. AB - Surgical management of chondrodermatitis nodularis chronica helicis by curettage is described. The curet directs the dissection. The necrotic cartilage is soft and is removed easily. The endpoint is reached when the curet is repelled by firm, elastic cartilage. Contours remain normal because the skin is tented over the defect supported by the remaining cartilage. PMID- 1757653 TI - Postoperative elevation of eyeglasses from the nasal bridge. AB - After surgery on the proximal nose, wearing eyeglasses can be difficult and uncomfortable. In addition, pressure on the skin underneath the eyeglass nose pads may modify wound healing. We describe simple techniques using readily available materials and optical devices that either reduce or remove pressure on the nose from eyeglasses. PMID- 1757654 TI - Re: Microliposuction and autologous fat transplantation for aesthetic enhancement of the aging face. PMID- 1757656 TI - The analgesia we've been waiting for? PMID- 1757655 TI - More on telescopic loupes. PMID- 1757657 TI - Characteristics of children of alcoholics: putative risk factors, substance use and abuse, and psychopathology. AB - A sample of 253 children of alcoholics (COAs) and 237 children of nonalcoholics (non-COAs) were compared on alcohol and drug use, psychopathology, cognitive ability, and personality. COAs reported more alcohol and drug problems, stronger alcohol expectancies, higher levels of behavioral undercontrol and neuroticism, and more psychiatric distress in relation to non-COAs. They also evidenced lower academic achievement and less verbal ability than non-COAs. COAs were given Diagnostic Interview Schedule alcohol diagnoses more frequently than non-COAs. The relation between paternal alcoholism and offspring alcohol involvement was mediated by behavioral undercontrol and alcohol expectancies. Although gender differences were found, there were few Gender X Family History interactions; the effects of family history of alcoholism were similar for men and women. When gender effects were found, they showed greater family history effects for women. PMID- 1757658 TI - Substance use and symptomatology among adolescent children of alcoholics. AB - This study assessed the magnitude and specificity of parental alcoholism as a risk factor for internalizing symptomatology, externalizing symptomatology, and alcohol and drug use in adolescence. We evaluated parents' and children's reports of symptomatology and children's reports of alcohol and drug use in a community sample of 454 adolescents. The results showed that parental alcoholism was a moderate to strong risk factor, with stronger risk associated with recent (rather than remitted) parental alcoholism. Multivariate analyses showed that the specificity of risk varied with the outcome measure. In predicting externalizing symptomatology, the risk associated with parental alcoholism was mediated by co occurring parental psychopathology and environmental stress. However, in predicting alcohol use, the father's alcoholism was a specific risk factor above and beyond the more generalized effects of stress and family disruption. PMID- 1757659 TI - Trance logic in hypnosis and imagination. AB - In 2 experiments we investigated trance logic, or the tolerance of logical incongruity, in age regression and hallucination. Experiment 1 tested 21 hypnotizable and 19 unhypnotizable subjects in an application of the real simulating model of hypnosis. Experiment 2 tested 26 high and 19 low imagery ability subjects in an adaptation of the model to the imagination context. Subjects' experiences were investigated through the experiential analysis technique. More real than simulating subjects displayed trance logic during age regression, but they did not differ on the major measures of trance logic during hallucination. This pattern of responding occurred in both the hypnosis and the imagination contexts. Subjects' comments suggested that completeness of and belief in age regression or hallucination may play some role in trance logic. The importance of understanding trance logic from the subject's point of view is discussed. PMID- 1757660 TI - Adjustment of children of depressed mothers: a 10-month follow-up. AB - There is considerable concern about the adjustment of children of depressed mothers. Earlier we studied the specificity of these difficulties to maternal depression. Child adjustment difficulties were evident in 7- to 13-year-old children of both depressed and nondepressed psychiatric patient mothers but not in the children of community mothers or nondepressed medical patient mothers (Lee & Gotlib, 1989a). This report describes a 10-month follow-up of 44 of these subjects. Despite the alleviation of maternal depressive symptomatology, children in the 2 psychiatric groups continued to manifest adjustment difficulties that were evident to both clinicians and mothers. These findings suggest that the adjustment difficulties found in the children of psychologically distressed mothers do not abate within the 1st year after the mothers' recovery. PMID- 1757661 TI - Worry is reasonable: the role of explanations in pessimism about future personal events. AB - This experiment examines one component of worry, elevated subjective probabilities of negative events, and attempts to elucidate the cognitive processes on which this is based. The results suggest that the pessimistic subjective probabilities shown by chronic worriers can be understood using general theories of judgment, specifically, by the use of the availability heuristic (Tversky & Kahneman, 1973). However, it is the availability of a particular pattern of cognitions--an increased accessibility of explanations for why a negative event would occur, combined with a reduced accessibility of explanations for why it would not--that is important. The results are integrated within a description of the worry process, and possible clinical applications through the use of reason-generation techniques are discussed. PMID- 1757662 TI - Dream of absent-minded transgression: an empirical study of a cognitive withdrawal symptom. AB - Among 293 smokers abstinent for between 1 and 4 weeks, 33% reported having at least 1 dream about smoking. In most dreams, subjects caught themselves smoking and felt strong negative emotions, such as panic and guilt. Dreams about smoking were the result of tobacco withdrawal, as 97% of subjects did not have them while smoking, and their occurrence was significantly related to the duration of abstinence. They were rated as more vivid than the usual dreams and were as common as most major tobacco withdrawal symptoms. In subjects abstinent for 1 year, 63% recalled having dreams about smoking. They had on average 5 of them, and about a quarter occurred after the 6th month of abstinence. Having dreams about smoking was prospectively positively related to maintenance of abstinence. An explanation of this finding based on the association of smoking in dreams with aversive emotions is offered. PMID- 1757663 TI - Parental affective style risk and the family system: a social relations model analysis. AB - Social relations model analysis was used to clarify family dynamics associated with parental affective style, an index of parent-to-child behavior associated with severe psychopathology in the child. Results from 70 families who had sought clinical services for an adolescent family member (39 girls and 31 boys) suggest (a) that adolescents elicit the negative parental affective style that puts them at risk and (b) that elicitation of negative parental affect is strongly tied to adolescents' expression of negative affect toward their parents (i.e., a reciprocity effect). The findings support the views that children contribute to their own risk of psychopathology and that parent-child behavior ought to be interpreted in the broader context of the family system. PMID- 1757664 TI - Cognitive motivation and drug use: a 9-year longitudinal study. AB - The predictive precedence of expectancy constructs, operationally defined as cognitive motivations, and drug use was investigated over a 9-year period from adolescence to adulthood. Alternative predictions from three different classes of theories of expectancy-behavior relations, including expectancy theory, a Skinnerian approach, and a reciprocal determinism perspective, were evaluated. The results are most consistent with the notion based in expectancy theory that cognitive motivations are nonspurious and possibly functionally autonomous influences on the use and abuse of drugs. More limited support is found for the view that drug use leads to cognitive motivations, as postulated in other theoretical perspectives. Other findings reveal the presence of expectancy generalization processes consistent with Rotter's (1954) expectancy theory, as well as the unique status of cognitive motivations for alcohol as an independent predictor of problem drug use. PMID- 1757665 TI - Do confidants of depressed women provide less social support than confidants of nondepressed women? AB - The prediction was tested that during a simulated telephone conversation, the confidants of depressed women would provide less social support than the confidants of nondepressed psychiatric and nonpsychiatric control women. The coded speech of subjects and their confidants indicated that (a) confidants echoed the positive or negative valence of the statements made by subjects; (b) depressed women exhibited more depressotypic speech than women in both control groups; (c) confidants of depressed women also made more depressotypic statements, possibly due to the echoing phenomenon; (d) contrary to prediction, there were no significant group differences in the sequential dependencies of responses that confidants made to depressotypic or antidepressotypic subject statements; (e) contrary to prediction, the affect of depressed women's confidants was not more negative. PMID- 1757666 TI - Clinical, neuropsychological, and brain structural correlates of smooth-pursuit eye tracking performance in chronic schizophrenia. AB - The relation of smooth-pursuit eye tracking dysfunction to neuropsychological performance, brain structural anomalies, and clinical state was examined in a sample of 61 patients with chronic schizophrenia. No association was found between impaired pursuit oculomotion and measures of chronicity or clinical state. Likewise, no association emerged between eye-tracking integrity and brain structural anomalies. Patients with dysfunctional eye tracking were more likely to have impaired performance on tests that assess frontal lobe functioning. In addition, negative symptoms and a relative absence of positive symptoms. Because negative symptoms are often found among patients with frontal lobe impairment, their association with abnormal eye tracking provides converging support for the hypothesis that the cortical locus of deviant smooth-pursuit eye tracking is in the frontal lobes. PMID- 1757667 TI - Left frontal hypoactivation in depression. AB - Baseline resting electroencephalogram activity was recorded with 3 different reference montages from 15 clinically depressed and 13 control subjects. Power in all frequency bands was extracted by fast Fourier transformation. There was a significant Group X Hemisphere interaction in the mid-frontal region, for the alpha band power only. Depressed subjects had less left-sided activation (i.e., more alpha activity) than did normal control subjects. This pattern of diminished left-sided frontal activation is interpreted as indicating a deficit in approach mechanisms in depressed subjects. PMID- 1757668 TI - Attribution and expressed emotion in the relatives of patients with schizophrenia. AB - Indexes of expressed emotion (EE) in 58 relatives of patients with schizophrenia were related to those relatives' spontaneously expressed causal beliefs about the illness and about related symptoms and behaviors. Relatives made attributions predominantly to factors external, universal, and uncontrollable from their own perspective, and to factors internal, universal, and uncontrollable from the patient's perspective. Low-EE relatives were similar in their attributions to emotionally overinvolved relatives. Compared with these two groups, critical and/or hostile relatives made more attributions to factors personal to and controllable by the patient. Subsequent analyses suggested that hostile relatives were further characterized by making more attributions to factors internal to the patient and by making attributions with fewer causal elements. PMID- 1757669 TI - Generation of stress in the course of unipolar depression. AB - The effect of stressful events on depression has been amply demonstrated, but the opposite relation is also important. I examined event occurrence over 1 year in 14 women with unipolar depression who were compared with demographically matched groups of women with bipolar disorder (n = 11), chronic medical illness (n = 13), or no illness or disorder (n = 22). Interview assessments of life events, severity, and independence of occurrence confirmed the hypothesis that unipolar women were exposed to more stress than the normal women, had significantly more interpersonal event stress than all others, and tended to have more dependent events than the others. The implication is that unipolar women by their symptoms, behaviors, characteristics, and social context generate stressful conditions, primarily interpersonal, that have the potential for contributing to the cycle of symptoms and stress that create chronic or intermittent depression. PMID- 1757670 TI - (Hu)man versus mean revisited: MMPI group data and psychiatric diagnosis. AB - A meta-analysis of Minnesota Multiphasic Personality Inventory (MMPI) data from 403 control and psychiatric samples was used to (a) examine demographics associated with previously published MMPI studies, (b) test Goldberg's (1972) indexes for predicting normal versus deviant and neurotic versus psychotic group membership, (c) compare multiple regression, discriminant function, and logistic regression analyses commonly used to study the relation between the MMPI and diagnostic group membership, and (d) examine the signal within the MMPI as it relates to current psychiatric diagnosis. Group data were found to be efficient indicators of the relation between the MMPI and diagnosis, although efficiency is compromised by within-sample heterogeneity. The 3 statistical methods examined obtained equivalent results. Regression models related to group prediction are presented. PMID- 1757671 TI - Responses to depression and their effects on the duration of depressive episodes. AB - I propose that the ways people respond to their own symptoms of depression influence the duration of these symptoms. People who engage in ruminative responses to depression, focusing on their symptoms and the possible causes and consequences of their symptoms, will show longer depressions than people who take action to distract themselves from their symptoms. Ruminative responses prolong depression because they allow the depressed mood to negatively bias thinking and interfere with instrumental behavior and problem-solving. Laboratory and field studies directly testing this theory have supported its predictions. I discuss how response styles can explain the greater likelihood of depression in women than men. Then I intergrate this response styles theory with studies of coping with discrete events. The response styles theory is compared to other theories of the duration of depression. Finally, I suggest what may help a depressed person to stop engaging in ruminative responses and how response styles for depression may develop. PMID- 1757672 TI - Maintenance of grip-induced muscle tension: a behavioral marker of schizophrenia. AB - A grip-induced muscle tension maintenance task distinguished between schizophrenic patients, regardless of medication or hospitalization status, and both normals and controls with affective (unipolar and bipolar) disorders. Unaffected first-degree relatives of schizophrenic patients also showed a grip deficit. Coupling the grip task with a visual discrimination task that divided attention through instruction or reinforcement contingency, increased grip error times for all groups. No group differences appeared on the discrimination task, regardless of difficulty level, and the tone used to provide corrective feedback was not implicated in the grip deficit. The results suggest that the grip task is tapping, in a systematic and reliable manner, a motor-control abnormality that may be useful as a behavioral marker of schizophrenia. PMID- 1757673 TI - Prevalence and correlates of postpartum depression in first-time mothers. AB - The prevalence and correlates of postpartum depression were examined in a large (N = 1,033) sample of married, primiparous, middle-class mothers of full-term, healthy infants; 9.3% met modified Research Diagnostic Criteria for depression. However, 39% of the nondepressed women also reported at least 1 somatic symptom. Depressed women whose symptoms were current obtained elevated scores on the Center for Epidemiological Studies-Depression scale, as did some women who did not meet depression criteria. Depressed women different from nondepressed women on several socioeconomic status indicators and the occurrence of obstetric complications, even in this low-risk sample. These data have implications for the assessment of depression in postpartum women. PMID- 1757674 TI - Early longitudinal course of acute-chronic and paranoid--undifferentiated schizophrenia subtypes and schizophreniform disorder. AB - This prospective longitudinal study examined symptoms and adjustment at 2 and 4 years posthospital discharge in Research Diagnostic Criteria (RDC) and Diagnostic and Statistical Manual (DSM-III) schizophrenia subtypes and in DSM-III schizophreniform disorder. Delusions, hallucinations, thought disorder, anxiety, depression, and specific areas of community adjustment were assessed at each follow-up. RDC acute and subacute schizophrenia and DSM-III schizophreniform disorder were associated with more satisfactory overall adjustment and lower frequencies of psychotic symptoms over time. No significant differences in the course of symptoms or adjustment were found between paranoid and undifferentiated schizophrenia subtypes. Schizophrenia subtyping schemes based on length of illness features appear more prognostically viable than do symptom-based approaches. PMID- 1757675 TI - Completed suicide in the gifted: a late comment on "suicide among gifted women". AB - A recent study by Tomlinson-Keasey, Warren, and Elliott (1986) found differences between completed suicides in Terman's sample of gifted children and comparison subjects. The present article suggests that the differences identified in Tomlinson-Keasey et al. may have been confounded by the fact that completed suicides are typically found to have higher levels of psychiatric disturbance than nonsuicides. Data are presented to illustrate that when the completed suicides in Terman's sample are matched for psychiatric disturbance with the comparison subjects, few differences are found. PMID- 1757676 TI - Psychometric detection of schizotypy: perceptual aberration and physical anhedonia in relatives of schizophrenics. AB - We administered scales of Perceptual Aberration (PERAB) and Physical Anhedonia (PHYSAN), traits that may be related to risk for schizophrenia, to 54 schizophrenics, 146 of their first-degree relatives (evaluated for schizophrenia related disorders), and 178 normal subjects (screened for psychotic disorders in them or their relatives). For both scales, there was a significant effect of group membership. For the PERAB scale, the schizophrenics had higher scores than the normal subjects, who had higher scores than the relatives. For the PHYSAN scale, schizophrenics had higher scores than their relatives, who had higher scores than the normal subjects. Patterns of familial correlations also suggested that physical anhedonia, but not perceptual aberration, may be familial among schizophrenics and their relatives. The PHYSAN scale, but not the PERAB one, may be a useful indicator of liability for schizophrenia among the relatives of affected probands. PMID- 1757677 TI - Reduction of perseverative errors in patients with schizophrenia using monetary feedback. AB - The influence of monetary feedback on Wisconsin Card Sort Test (WCST) performance of 14 male schizophrenics was investigated. Patients were administered the test under standard instructions and with monetary feedback in counterbalanced order. Monetary reinforcement reduced perseverative errors and increased correct responses (p less than .05). These findings suggest that the WCST perseverative errors of schizophrenics reflect motivational as well as cognitive factors. PMID- 1757678 TI - Inequalities in health and primary health care nursing. PMID- 1757679 TI - Self-activeness and the need for help in domiciliary care. AB - The data in this paper are based on interviews of domiciliary care patients in Helsinki, Finland. The aim of the study was to compare self-active patients' (65) and non-self-active patients' (61) need for help and the help they received. The findings demonstrated that patients who had, to some extent, a 'better' background, received support from their relatives, assessed themselves as physically and especially mentally healthier and were socially stronger, were also more often self-active than patients, who had a 'poorer' background, received little support and felt more ill. The non-self-active patients received help with some physical activities more often but not with mental and social problems. The self-active patients co-operated better with the care providers and considered the quality of care to be higher than did the non-self-active patients. PMID- 1757680 TI - A case study: perspectives on a self-care deficit nursing theory-based curriculum. AB - This case study provides a descriptive analysis of administrative, faculty and student perspectives on use of and satisfaction with Orem's Self-Care Deficit Nursing Theory (SCDNT) in one baccalaureate nursing programme's curriculum elements of (a) goals and objectives, (b) materials, (c) content, (d) nursing foci, and (e) evaluation. The need for such an analysis is indicated by the wide acceptance and use of the SCDNT in education and the absence of any similar study. Curriculum is conceptualized in the context of the Curriculum Model for the Study of Schooling, USA. Administrative representatives included the dean of nursing, the director of the nursing programme, the two curriculum chairpersons and the programme co-ordinator. The faculty and students from two specific courses provided the instructional and experiential perspectives. Data collection included structured personal interviews and document review. The investigator developed from the ideal perspective of the literature (Orem and related scholars) criteria for judging if the SCDNT indeed was implemented in the curriculum elements and the satisfaction with the theory. The faculty perspective was the most similar to the ideal, and the administration's was the least similar. Student and faculty perceptions were extremely similar. All three perspectives were in near agreement with the ideal on the use of the SCDNT in: goals and objectives, content and evaluation. A major inconsistency was found. Each perspective expressed varying interpretations of the nursing process. Pronounced patterns were examined, and implications for nursing education were stated. PMID- 1757681 TI - Psychosocial predictors of healthy behaviours in women. AB - The link between psychosocial factors and various health problems may be partially explained by the relationships of these factors to healthy behaviours. The relationships of anger experience, anger expression, hostility and hardiness to healthy behaviours was investigated in 97 healthy women. In multiple regression analysis, 25% of the variance in healthy behaviour was accounted for by hostility (12.5%), education (added 7.5%), and the combination of high anger experience/high anger-out (added an additional 5%). This was especially significant in view of the significant relationship of hostility to both anger experience and anger out. Although hardiness showed a significant positive correlation (r = 0.23 P less than 0.05) with healthy behaviours, it did not enter the multiple regression equation. The negative effects of hostility and chronic experience and overt expression of anger emerged as stronger than any positive association between hardiness and healthy behaviours. Implications for nursing include anger recognition and constructive management as areas of education and support. These interventions should assist women in managing their health better and will provide fruitful areas for further study. PMID- 1757682 TI - The effect of an intervention programme on interactions on a continuing care ward for older people. AB - This study describes a project designed to enhance the quality of life of older people on a continuing care ward. The aim of the interventions used was to increase staff/resident interaction levels. The programme interventions focused on staff education and extra ward activities. Interaction levels were measured using a previously published observation schedule which was adapted for use with this client group. Inter-rater reliability measures indicated that the adapted measure was still reliable. The patients on the ward were also assessed to establish their level of dependency. The findings indicated that, for the majority of observational categories, there were no significant differences, but those that were found were in the opposite direction to that predicted and indicated a reduction in interaction levels. Possible explanations for this finding are discussed. PMID- 1757683 TI - Nurses as role models and health educators. AB - This paper focuses on the role of the nurse as both a role model and as a health educator and examines some key areas where tension between these two appear to exist. The context is the changing British National Health Service and the expectations of both the providers of the care and the consumers. The concept of the nurse as a role model for health is explored: the use of the term 'role' and its implications for nurses; what being a role model might mean for nurses and some of the stresses which living up to these role models might impose; the extra burden of an implied healthy role model and the expectations which are placed on nurses from both within and outwith the profession. Communication theory and the view of the nurse as a 'credible source' may add to these pressures and this paper tries to offer to nurses an alternative standpoint from which they may begin to tackle their health promotion/education activities. The traditional role of the nurse as a health educator is examined and a variety of options are offered to encourage nurses to consider their approach to dealing with clients within the context of health education. Some different models of education which are more suitable for the flexible approach which is required for health education are outlined. The paper closes with some discussion points which suggest that self-awareness and personal developments may be among the most important qualities which nurses need to be effective health educators. PMID- 1757684 TI - Are nurses good patient educators? AB - Health care demands are rising rapidly as we move towards the year 2000 and effective health education is essential if increasing numbers of patients are to be nursed in the community and the effects of preventable illnesses are to be minimized. It is therefore extremely pertinent to discuss how well nurses are educating their patients at present and what strategies the profession may need to consider in order to meet educational needs of the future. It seems clear that nurses have a responsibility to provide the information that their patients require, although there remains some debate regarding whether they are the most appropriate member of the health care team to do so. Recent studies show that nurses can be effective educators. However, although many recognize the importance of this role, they still often lack the skills, knowledge, motivation and support required to organize and implement an adequate programme of patient education. PMID- 1757685 TI - Older adults: factors that predict the use of over-the-counter medication. AB - Previous research has found over-the-counter (OTC) medication use not easily predicted from physical symptom experience. The purpose of this study was to examine the relationship between older adults' use of OTC medications and mood, social, health and demographic variables. Interviews were conducted with 186 adults aged 65 to 99 years. The mood variables of anxiety and depression were measured by the Profile of Mood States. The quality and degree of intimacy in a social relationship was measured by the Emotional Bondedness Scale. OTC medication use was measured by assessing frequency of OTC medication use, the total number of categories of OTC medication used, and the use of OTC medications in response to symptoms. Subjective health appraisal, number of chronic illnesses, number of prescriptive medications, the number of symptoms experienced in the previous month, and physician-office visit frequency were recorded. OTC medication use was predicted by the total number of symptoms experienced, emotional bondedness, age, anxiety, income, cohabitation status, and the frequency of physician-office visits. The total number of symptoms experienced accounted for more variance in OTC medication use than any other variable. PMID- 1757686 TI - Ageist attitudes among young adults: implications for a caring profession. AB - It is frequently suggested that younger adults are negative in their attitudes toward elderly people. There are also claims that such attitudes develop as a result of the socially constructed phenomenon of ageism. This paper briefly addresses the concept as it is presented in the literature and goes on to describe an attitudinal study which supports the existence of ageism. An Attitudes Toward the Elderly inventory was administered to secondary school pupils during their final 2 years of schooling, to student nurses at the very beginning of their training and to qualified nurses. It was found that the subjects did demonstrate negative attitudes and that there appeared to be a definite gender socialization influence, with females demonstrating less negative attitudes than males. Contrary to expectations, entry into nursing did not lead to more positive attitudes but had the converse effect. The influence of ageism and more specific professional socialization processes are suggested as explanations for these patterns. Implications for nursing and other occupational groups involved in caring for the elderly are discussed. PMID- 1757687 TI - A quality of life study of discharged long-term psychiatric patients. AB - A survey of 48 discharged long-stay patients was carried out. The purpose of the survey was to identify the patients' perceptions of: (a) the preparation given to them in the rehabilitation wards prior to discharge; (b) the quality of their life in the community; (c) the care given by the community psychiatric nurses. A structured interview was conducted in the ex-patient's own home and objective measures of quality of life were also used. Most patients felt that they were well prepared for discharge. More received skills training then received health education. Every respondent (48, 100%) preferred living in the community to being in a psychiatric hospital. Most respondents (46, 95%) were satisfied with life in general. Twenty-eight were visited by community psychiatric nurses and 24 (85%) were satisfied with the care given. PMID- 1757688 TI - Nurses' hands as vectors of hospital-acquired infection: a review. AB - Hospital-acquired infections (HAI) are notorious for the manner in which they complicate the course of the original illness, increase costs of hospital stay and delay recovery. This review will briefly outline the problems presented by HAI in developed countries and present evidence that Staphylococcus aureus and gram negative bacilli, the main causative agents, reach susceptible patients via the contact rather than airborne route, predominantly on the hands of hospital staff. Good hand hygiene could help reduce the economic burden and patient distress caused by HAI, but there is evidence that it is infrequently and poorly performed by nurses, the health care staff most frequently in continuous contact with patients. Possible reasons are explored in an attempt to identify strategies to improve hand hygiene. PMID- 1757689 TI - The outcome and experiences of first pregnancy in relation to the mother's childbirth knowledge: the Finnish Family Competence Study. AB - The possible influence of the expectant mother's knowledge of childbirth on the outcome and experience of pregnancy and labour was investigated by means of a postpartum questionnaire in 1238 primiparae. The mothers were divided into two groups according to their basic childbirth knowledge. At birth, the conditions of newborns were equal in both groups when judged by Apgar scores. The low knowledge level group had small-for-gestational-age babies more frequently and these babies were also treated in the paediatric ward more frequently than those in the high knowledge group. The latter group was significantly more critical towards the staff of the delivery room and the postnatal ward; the fathers of this group were also present at delivery significantly more frequently. The low knowledge level group was significantly more unwilling to have another pregnancy in the near future or ever. The results indicate that low childbirth knowledge is associated with a poorer pregnancy outcome. It is a message to antenatal care staff of the need for support, supplementary education and careful obstetric surveillance. Low childbirth knowledge may imply a set of problems, including those in interparental relationship, socio-economic situation and need for close surveillance and improved education. PMID- 1757690 TI - Continuing nursing education: some issues. AB - In nursing, a commitment to continuing education appears to be a relatively new concept. There have always been nurses who are continuing learners throughout their professional lives. Too often, this is incidental, rather than planned. There appears to be a need to re-examine current approach in continuing nursing education. PMID- 1757691 TI - Teaching activities of clinical instructors during the direct client care period: a qualitative investigation. AB - The lack of substantial research in the area of clinical teaching would suggest that this 'heart' of the nursing student's professional education has long been neglected. Employing a qualitative descriptive methodology, this study explored the teaching activities that nine clinical instructors said they implemented during the direct client care period and the teaching activities that these nine clinical instructors said they would implement in response to a specific scenario of a clinical teaching event. The unstructured interviews revealed that clinical instructors: (a) noted role modelling the greatest number of times as a teaching activity but implemented it less frequently; (b) used verbalizations in the form of telling, asking, saying, discussing or talking as the primary teaching activity in the clinical area and in response to the specific scenario; (c) do not have opportunities to see other clinical instructors teaching in the clinical area; (d) have difficulty separating teaching activities and evaluation activities; (e) are eclectic in their use of learning theories; and (f) find articulating teaching activities that they implement during the direct client care period to be a complex task. PMID- 1757692 TI - First-line nurse managers: issues in the literature. AB - The purpose of this paper is to describe the major issues from the literature which confront first-line nurse managers. The increasingly complex environment in which these managers function has, at the very least, significantly altered their role. However, there are other issues confronting those in first-line positions and these are discussed under four broad headings: the role of first-line nurse managers; role conflict and confusion; management skills and functions; and education for first-line nurse managers. PMID- 1757693 TI - The conflict management style of staff nurses and nurse managers. AB - Conflict is recognized as being a common occurrence in both everyday personal and professional nursing life, and it is now generally agreed that conflict can be both problematic and potentially beneficial to both individuals and organizations. There is a large amount of anecdotal and narrative literature about the nature and sources of conflict which fails to reflect upon the complexities and theoretical perspectives that exist. There are also few research studies which examine the nature of nursing conflict and how conflict is managed by nurses in the workplace. This study presents a review of some aspects of conflict and its management and specifically investigates the conflict management style of staff nurses and nurse managers in the hospital setting. The results suggest that avoidance is the most commonly used conflict management strategy, with competition being the least favoured. PMID- 1757694 TI - Regulation of temporary nursing services--what does it mean? PMID- 1757695 TI - Interfacing nursing and biologic science. PMID- 1757696 TI - Undoing the habit of hostility. PMID- 1757697 TI - The Midwest Nursing History Resource Center. PMID- 1757698 TI - Health promotion--a cultural affair. PMID- 1757699 TI - Substitute decision makers in health care treatment decisions. PMID- 1757700 TI - Accountability for quality improvement--patients' right to assess the plan of care. PMID- 1757701 TI - The hospital admitting process--a practice perspective. PMID- 1757702 TI - Policy at the grassroots: community-based participation in health care policy. AB - American Health Decisions is a developing social movement that aims to work at the grassroots level to educate people about issues and problems in health care and to promote public involvement in decision making about health policy. The movement offers nurses opportunities to expand their traditional commitment to involving people in decisions about their health. By promoting the development of the movement, nurses can contribute to the creation of a structured process of direct public participation in policy decisions related to health care. Nurses may have a special role to play in the movement by promoting the participation of low-income people. PMID- 1757703 TI - The concept of integration: a foundation for evaluating outcomes of nursing care. AB - Changes in the health care environment, an aging population, and an increase in chronic health conditions require consideration of the adequacy of concepts available for demonstrating the effectiveness of nursing care. One concept that has potential utility for nursing in this regard is the concept of integration. Analysis of the concept of integration was conducted to alleviate existing ambiguity and to explore ways in which this concept has been employed in diverse disciplines. The concept of integration is characterized primarily as a process of combination: two or more elements are merged with sufficient interaction so that unity of the newly formed entity is achieved. The attributes of the concept of integration, therefore, include process, combination, interaction, and unity. The concept of integration is useful in evaluation of reconciliation of past and present identities and altered role relationships within the environment. PMID- 1757704 TI - Radical reflection as a theoretical framework in nursing using acquired immunodeficiency syndrome as example. AB - The purpose of this article is to present a critical theoretical analysis of society's view of the acquired immunodeficiency syndrome (AIDS) epidemic. The method of radical reflection that was developed by Jan Thompson in 1983 is used as the framework of analysis. Through the five steps of Thompson's method (bracketing, historical recovery, critique, dialectical imagination, and negotiation), the dominant societal ideology of AIDS is identified, placed in an historical context, and examined through the process of Habermasian critique. From this knowledge, a more liberating type of social reality can be envisioned, allowing for the forging of a more egalitarian health care system. Radical reflection can be used by both professional and student nurses to explore and evaluate other health issues. Illness must not be approached and thought of outside of and detached from the major problems of society. PMID- 1757705 TI - Validation of defining characteristics of four nursing diagnoses using a computerized data base. AB - As the use of nursing diagnoses in clinical practice increases, systematic research is necessary to appropriately validate them. Validity studies could be expedited by the use of information technology and computerized clinical data bases. The purpose of the following descriptive study was to validate the defining characteristics (risk factors for potential diagnoses) of the four nursing diagnoses related to alterations in fluid volume proposed by the North American Nursing Diagnosis Association using a nursing minimum data set (NMDS) collected from a computerized nursing data base. A sensitivity measure, the proportion of subjects with specific defining characteristics for a given diagnosis among the total number of subjects with the respective diagnosis, was used to estimate validity. The study was conducted in a 265-bed, mid-western, community hospital in which computerized nursing diagnosis care planning is used. The elements of the NMDS and defining characteristics were collected from a systematic sample (N = 191). The sample consisted of a proportion of about half of computerized discharge patient care plan summaries from each of the four diagnostic labels related to alteration in fluid volume obtained from medical records during the 1987 calendar year. Discharge patient care plan summaries contained at least one of four nursing diagnoses related to alteration in fluid volume. The results show the existence of individual defining characteristics as well as combinations of defining characteristics meeting validation criteria for each diagnostic label. Never-documented defining characteristics also were identified. PMID- 1757706 TI - Developing faculty expertise in culturally focused care and research. AB - The faculty development program was designed to extend expertise in culturally focused nursing care and research. Its main purposes were to operationalize the concept of culture in clinical practice settings and to stimulate culturally focused nursing research. The program was an interdisciplinary collaborative effort with content grounded in anthropological concepts and research methods. Content was divided into four phases: concepts basic to culturally focused care; use of research findings in the clinical area; methodological issues in culturally focused research; and analysis of culturally focused research proposals. The program resulted in greater integration of the concept of culture into theory and practice and in the development of several funded research proposals. PMID- 1757707 TI - Education-practice partnerships: faculty practice as faculty development. AB - The importance of establishing service-education partnerships in nursing is well recognized. Many such associations will include provisions for faculty practice, ideally occurring within the context of a comprehensive program that advances clearly stated goals put forth by all participants. We describe the continuing clinical education component of faculty practice, and discuss its place within a hypothetical, broader program. Faculty practice is conceptualized as one aspect of ongoing faculty development. PMID- 1757708 TI - Somatization symptoms in pediatric abdominal pain patients: relation to chronicity of abdominal pain and parent somatization. AB - Symptoms of somatization were investigated in pediatric patients with recurrent abdominal pain (RAP) and comparison groups of patients with organic etiology for abdominal pain and well patients. Somatization scores were higher in RAP patients than well patients at the clinic visit, and higher than in either well patients or organic patients at a 3-month followup. Higher somatization scores in mothers and fathers were associated with higher somatization scores in RAP patients, but not in organic or well patients. Contrary to the findings of Ernst, Routh, and Harper (1984), chronicity of abdominal pain in RAP patients was not significantly associated with their level of somatization symptoms. Psychometric information about the Children's Somatization Inventory is presented. PMID- 1757709 TI - Popular and aggressive boys' initial social interaction patterns in cooperative and competitive settings. AB - Thirty-two third- and fourth-grade popular and aggressive boys were observed individually attempting to enter a game being played by a mixed-status unfamiliar peer dyad in both competitive and cooperative game settings. Consistent with previous findings, popular entry children were accepted more readily into the game situation than were aggressive children. Popular children tended to approach the situations using more prosocial questions while their aggressive peers tended to use demands. More differences in entry strategies were noted in the competitive than in the cooperative game setting. While most entry children directed their first entry bid toward the aggressive game host, they reported having liked the popular game host best when the game was finished. Additionally, the quality of game interactions was observed to become more positive following a popular child's entry, while becoming more negative following an aggressive child's entry. The results are discussed in terms of leadership roles and implications for both assessment and intervention settings and strategies. PMID- 1757710 TI - Effects of background anger, provocation, and methylphenidate on emotional arousal and aggressive responding in attention-deficit hyperactivity disordered boys with and without concurrent aggressiveness. AB - We investigated the effects of background anger, provocation, and methylphenidate on emotional, physiological, and behavioral responding in children with attention deficit hyperactivity disorder (ADHD) with and without concurrent aggression. Our study revealed that ADHD boys showed more emotional and physiological distress when exposed to an interaction in which an administrator chastised each boy's favorite counselor, compared to a friendly interaction between the two adults. The background anger manipulation did not affect the aggressive behavior of the boys against an opponent in an aggressive game. High-aggressive (HA) ADHD boys were more likely to respond to provocation with aggression than low-aggressive (LA) ADHD boys, but only LA boys showed increased physiological reactivity with increasing provocation. Methylphenidate resulted in increased heart rates under all conditions and did not interact with any of the other findings. PMID- 1757711 TI - Childhood peer rejection, aggression, withdrawal, and perceived competence as predictors of self-reported behavior problems in preadolescence. AB - Childhood peer rejection, aggression, withdrawal, and perceived competence were compared as predictors of self-reported behavior problems. Peer sociometric status (Coie, Dodge, and Coppotelli, 1982), teacher ratings of behavior problems (Lorion, Cowen, & Caldwell, 1975), and perceived competence ratings (Harter, 1982) were obtained for 613 second- through fourth-grade children. Two years later, these students completed a modified version of the Youth Self-Report from (Achenbach & Edelbrock, 1987). Rejected children and neglected girls were more likely to have a self-reported nonspecific negative outcome than others. Neglected girls were at heightened risk for depression. A varied set of predictors obtained from different informants emerged for each sex for each of the specific self-reported outcomes of depression, unpopularity, delinquency, aggression, and self-destructive/identity problems. Results are discussed in terms of future directions for longitudinal research on the consequences of poor peer relationships in childhood. PMID- 1757712 TI - Salivary testosterone and cortisol among late adolescent male offenders. AB - The relationship of salivary testosterone and cortisol concentrations to personality, criminal violence, prison behavior, and parole board decisions was examined among 113 late-adolescent male offenders. Offenders high in testosterone committed more violent crimes, were judged more harshly by the parole board, and violated prison rules more often than those low in testosterone. No main effects for cortisol emerged. However, as expected, a significant interaction between testosterone and cortisol was found, in which cortisol moderated the correlation between testosterone and violence of crime. Cortisol may be a biological indicator of psychological variables (e.g., social withdrawal) that moderate the testosterone-behavior relationship. Paper and pencil measures of personality and behavior showed little relationship to hormones. PMID- 1757713 TI - Auditory attention switching in hyperactive children. AB - The ability to rapidly reorient attention in the auditory modality was studied in hyperactive children. Hyperactive and nonhyperactive subjects matched on age, sex, and IQ listened to dichotically presented lists for prespecified targets. Reorientation was studied by comparing performance on trials requiring subjects to reorient their attention during a list to performance on trials requiring no switching of attention. The results indicate that although nonhyperactive children were temporarily disrupted by the switch, they eventually reoriented to the cued ear. In contrast, once hyperactive children were disrupted by the switch, they did not reorient to the cued ear. As the pattern in performance comparing hyperactive and nonhyperactive subjects resembles the pattern previously found in comparing younger and older subjects, these results are consistent with the hypothesis that the auditory reorientation skills of hyperactive children are developmentally immature. PMID- 1757714 TI - Assessment of peer rejection and externalizing behavior problems in preschool boys: a short-term longitudinal study. AB - We examined the longitudinal stability of measures of negative peer status and aggressive-disruptive behavior in preschool boys. Subjects were 53 white 4- to 5 year-old boys from low-income family backgrounds. Peer sociometric measures of rejection and behavioral deviance were assessed in the fall and spring of the preschool year. Complementary measures were also obtained from teachers at both assessment points. Half of the boys designated as rejected on the basis of peer nominations maintained this status at the end of the preschool year. Teachers and peers did not agree on their selections of socially rejected children, but had good agreement concerning the identification of children with externalizing-type behavior problems. Finally, teacher and peer classifications of aggressive disruptive children were highly stable throughout the preschool year. These findings indicate that peer-rejected children can be identified at very young ages, and that preschoolers can be reliable informants about the social maladjustment of peers. PMID- 1757715 TI - Epidemiology, demography and definitions. PMID- 1757716 TI - Pharmacological and biochemical aspects of therapy-resistant depression. PMID- 1757717 TI - Treatment resistant or irresolutely treated? PMID- 1757718 TI - Prediction, treatment and prognosis of chronic primary major depression. PMID- 1757719 TI - Practical issues in managing bipolar depression. PMID- 1757720 TI - Psychosurgery for resistant depression: progress and problems. PMID- 1757721 TI - Factors distinguishing samples of lesbian and heterosexual women. AB - This study utilized non-clinical samples of women and examined historical, familial, sexual, and attitudinal variables to assess differences between groups endorsing heterosexual or homosexual orientations. Drawing from social learning theory, researchers expected the lesbian group to report more negative childhood sexual experiences with males, more positive childhood sexual experiences with females, more accepting parental attitudes toward sexuality and sexual experimentation, and more distant relationships with parents. Results indicate that, rather than childhood sexual experiences distinguishing groups, respondents' current attitudes are significant between-group discriminators. These findings are consistent with the recent body of literature that suggests that sexual orientation cannot be explained in terms of early sexual trauma or negative heterosexual experiences. PMID- 1757722 TI - AIDS and homophobia among nurses. AB - The purpose of this research was to study nurses' attitudes toward homosexuality and caring for homosexual patients. The results reported in this article are a component of a larger study of nurses' knowledge about and attitudes toward caring for patients with AIDS. The sample comprised 581 Registered Nurses residing in Erie County, New York. Data were gathered by mailed questionnaires. Results of the study indicate that issues concerning the care of patients with AIDS may be complicated by the fact that many of these individuals are homosexuals. The results of this research provide data for developing intervention strategies to help nurses cope with their concerns about caring for homosexual patients with AIDS. PMID- 1757723 TI - A survey of gay/lesbian Catholics concerning attitudes toward sexual orientation and religious beliefs. AB - The negative assessment of lesbian/gay relationships in Catholic circles is most often based on scanty information gathered from folklore, the commercial media, and a narrow, literal reading of Biblical texts. Assumptions are made about the personal adjustment of individual gay/lesbian persons and the quality of their relationships without recourse to actual lived experience. This survey of 263 gay/lesbian Catholics and 20 controls was designed to receive direct feedback from lesbian/gay persons concerning their religious attitudes, personal adjustment, and relational quality. The results contradict many preconceptions, and a remarkable similarity is demonstrated between the gay/lesbian responses and those of the control group. PMID- 1757724 TI - Homosexuality, class and the church in nineteenth century England: two case studies. AB - This article seeks to reconstruct and contrast two episodes in the nineteenth century Church. Both involved churchmen, Bishop Percy Jocelyn and Dean Charles Vaughan, in homosexual incidents. The second episode, that of Dean Vaughan, has been reconstructed for the first time using the Broadlands Manuscripts of Lord Palmerston. The most interesting aspect of these events is the response of the "establishment" to homosexuality. There seems little doubt that attitudes of the "establishment" were determined largely by class. The "establishment" would not officially condone homosexual behaviour, but in both cases (to varying degrees) it seems to have acted toward these men with latitude. One was able to evade justice, the other denied a mitre but otherwise allowed advancement in the Church. Both incidents provide evidence that persecution of homosexuals was something confined to the lower orders; and that the discreet middle class or aristocratic homosexual could rely on his class for protection. Perhaps integral to this tolerance was a Victorian taste for self-denial. The homosexual who treated his sexuality as a curse and a source of tragedy was more likely to attract the tolerance of his peers than the homosexual who acknowledged his sexuality to the full. PMID- 1757725 TI - "Homosexual occupations" in Mesoamerica? AB - Data gathered among self-identified homosexual men in Guatemala City and Mexico City call into question the intrinsic connection between homosexuality and occupational choice posited by Whitam and Mathy (1986). Concentrations of homosexual men in some occupations can be explained as effects of discrimination and of the normal transmission through personal networks of information about job opportunities, and does not require recourse to any innate drive for homosexual men to be actors, hairdressers or interior decorators. PMID- 1757726 TI - Military policies regarding homosexual behavior: an international survey. AB - The military attaches of 110 non-Communist embassies in Washington, DC, were surveyed from 1982-1984 regarding their countries' military policies about homosexuality. Of the 57 that responded, 37% reported policies excluding persons who engage in homosexual behavior from military service, 14% reported policies that accept homosexual and bisexual persons, and 49% reported having no policies about homosexual behavior. Cultural factors appear to be related to the military policies. PMID- 1757727 TI - Perspectives of CCK antagonists in pancreatic research. Part II. Experimental studies. AB - In this article, the effects of different classes of cholecystokinin (CCK) receptor antagonists in CCK-related physiological processes of the pancreas have been discussed. Both glutaramic acid derivatives and natural (benzodiazepine) analogs are potent, competitive antagonists of peripheral CCK receptors. These compounds thus provide a powerful tool for investigating the physiological and pharmacological actions of CCK in the gastrointestinal system, and have already clarified the role of CCK in pancreatic secretion and trophism or growth. PMID- 1757728 TI - Quantitative measurement of fibrosis in pancreatic tissue. Evaluation of a colorimetric method. AB - A colorimetric method has been used to quantify the collagen contained in 23 specimens of pancreatic tissue (11 controls and 12 chronic pancreatitis). The method takes advantage of the selective capacity of Sirius red to stain collagen protein and of rapid green to stain noncollagen protein. The results obtained by this method were compared with those of standard morphometry to determine tissue fibrosis. With the morphometric method, the values of the control group were 6.6 +/- 4.0% (fiber area/total area), and those of chronic pancreatitis 66.0 +/- 19.0% (difference 59.4, 95% confidence interval for difference: 47.2-71.6, P less than 0.001). The values obtained with the colorimetric method were 89.1 +/- 11.6 micrograms collagen/mg total protein in the control group, and 132.7 +/- 25.3 micrograms collagen/mg total protein in the chronic pancreatitis group (difference 43.6, 95% confidence interval for difference: 26.3-61.0, P less than 0.001). A highly significant correlation (r = 0.847; p less than 0.001) was observed between the amount of collagen measured colorimetrically and the degree of fibrosis determined morphometrically. These results demonstrate that the colorimetric method is a reproducible, simple, and rapid technique to quantitate fibrosis in histological preparations of pancreatic tissue. PMID- 1757729 TI - Independence of GIP-induced insulin secretion from sympathetic and parasympathetic innervation in the isolated perfused rat pancreas. AB - The incretin candidate GIP (gastric inhibitory polypeptide) is released from the gut by nutrients and can stimulate insulin secretion. Metabolic and hormonal factors have been shown to modulate insulin response to GIP. It is unknown, however, whether the autonomic nervous system, which itself controls insulin secretion, can modulate the insulinotropic effect of GIP. In the isolated perfused rat pancreas, we therefore investigated the influence of sympathetic and parasympathetic agonists and antagonists on the insulin response to GIP. As compared to control (6990 +/- 890 microU/10 min), the effect of either acetylcholine (29030 +/- 4600 microU/10 min), atropine (5880 +/- 1740 microU/10 min), norepinephrine (2520 +/- 750 microU/10 min), phentolamine (11380 +/- 1910 microU/10 min), isoproterenol (12740 +/- 2090 microU/10 min), propranolol (5600 +/- 880 microU/10 min), or GIP (29660 +/- 4490 microU/10 min) on insulin secretion was consistent with previous reports. The effects of the combined administration of GIP and either acetylcholine (48140 +/- 7540 microU/10 min), phentolamine (43930 +/- 4490 microU/10 min), norepinephrine (9000 +/- 1740 microU/10 min), or isoproterenol (36280 +/- 5210 microU/10 min) on insulin release were additive. Insulin response to GIP was resistant to atropine (24210 +/- 9470 microU/10 min) and propranolol (26450 +/- 4930 mu/10 min). We conclude that both GIP and the autonomic nervous system influence insulin secretion, but that they do so independently from each other. PMID- 1757730 TI - Influence of anoxia, reoxygenation, and uncoupling on survival, respiration, and trypsin-inhibiting capacity of isolated pancreatic acinar cells. AB - In the pathogenesis of acute pancreatitis, the events and mechanisms increasing the digestibility of the pancreatic acinar cells are widely unknown. Therefore, the possible contribution of a disturbed energy supply (provoked by anoxia or partial uncoupling) to the induction of autodigestion was studied in experiments on acinar cells isolated from the pancreas. During incubation viability, respiration under normal and maximally stimulated conditions, and trypsin inhibiting capacity (TIC) of these cells were determined. With increasing duration of anoxia, the portion of surviving cells was strongly diminished, and the number of cells with blebs and vesicularly transformed endoplasmic reticulum was increased. Although the endogenous respiration was not influenced up to 1.5 h of anoxia, 30 min of anoxia substantially decreased the capacity of oxidative energy production. The survival curves were characterized by a self-accelerating course of cell destruction. The alteration of the cellular energy metabolism found its reflection in the decreased TIC of the cells. PMID- 1757731 TI - Cystic endocrine tumor of the pancreas. AB - A large cystic tumor in the pancreatic body was found incidentally in an 85-yr old male. A distal pancreatectomy was performed after a diagnosis of cystadenocarcinoma. Microscopic examination of the resected specimen revealed a pancreatic cystic endocrine tumor; however, this tumor produced no symptoms. Immunohistochemical studies of the tumor cells showed positivity for gastrin, neuron-specific enolase, chromogranin A, and synaptophysin, and two cell types of neurosecretory granules were recognized in electron-microscopic studies. Although endocrine tumors of the pancreas are usually solid and cystic change occurs only rarely, such tumors should be considered in the differential diagnosis of patients who have a cystic lesion in the pancreas. PMID- 1757732 TI - Influence of the CCK-antagonist loxiglumide on bile-induced experimental pancreatitis. AB - The present study investigates the effect of CCK-receptor blockade on taurocholate-induced pancreatitis in rats using the potent antagonist loxiglumide. Intraperitoneal administration (50 mg/kg) of loxiglumide began 3 h before, or 10 min or 3 h after induction of pancreatitis. Mean survival times of the experimental groups were 31.2, 23.6, and 20.5 h, respectively, compared to 18.2 h for controls. Survival for 24 h after induction of pancreatitis was significantly improved when the antagonist was given 3 h before, but not in the time periods after induction. After 72 h, survival time was not significantly altered in any of the groups. Furthermore, amylase and lipase levels quantified 10 h after induction of pancreatitis in ascites, blood, or tissue did not indicate a significant difference, nor was improvement in survival seen when the CCK-antagonist was tested in rats receiving a basal treatment with intravenous volume substitution, peritoneal lavage, and protease inhibition. We conclude that CCK-receptor blockade does not improve the final outcome of bile-induced pancreatitis in the rat, even if treatment is started before induction of pancreatitis. PMID- 1757733 TI - Creatine phosphate as energy source in the cerulein-stimulated rat pancreas study by 31P nuclear magnetic resonance. AB - Stimulation of the rat exocrine pancreas by cerulein induces a variety of cellular processes, some of which require the expenditure of energy. In this study, changes in the amounts of various energy metabolites, including creatine phosphate (PCr), ATP, and ADP were determined by high-resolution 31P NMR spectroscopy. The spectrum of a perchloric acid extract of pancreas from the 48 h fasted rat was taken as a reference for comparison of 31P NMR spectra recorded after stimulation by cerulein. The NMR results obtained from rat pancreas stimulated in vivo by cerulein (3, 5, 10, 20, 40 min) were compared to those determined by HPLC. We show that during hormonal stimulation, the relative concentrations of PCr in the pancreas of the fasted rat rise significantly (p less than 0.02), reach a maximum at 10 min, fall between the 10th and 20th min, and then return to the relatively low levels observed in controls. On the other hand, the relative concentrations of ATP fall during the first 10 min after stimulation by cerulein, then rise significantly between the 10th and 20th min, whereas the levels of ADP rise during the first 10 min and fall between the 10th and 20th min. The energy required for exocytosis was assumed to be supplied by ATP synthesized in acinar cells. The 31P NMR results indicated that this ATP was derived from phosphorylation of ADP by PCr, and that large amounts of PCr are synthesized during the first minutes after cerulein stimulation. In addition, a significant rise in glycerophosphocholine was observed after cerulein stimulation, which was attributed to an enhanced catabolism of membranes and an increase in phospholipid turnover. Injection of cerulein antagonists, such as asperlicin or lorglumide, inhibited the effects of cerulein stimulation on energy metabolites. Furthermore, no changes were observed after injection of secretin, a hormone that stimulates secretion of bicarbonate. However, the analog of cerulein, pentagastrin, produced the same effects as cerulein, although to a lesser extent. PMID- 1757734 TI - The activation of beta-substituted nitrosamines that are carcinogenic to the pancreas. PMID- 1757735 TI - Do gallstones cause chronic pancreatitis? AB - Gallstones are well known to cause acute pancreatitis. However, the role of gallstone disease in the causation of chronic pancreatitis is still controversial. Abnormalities of the pancreatic duct have been noted in about one half of patients with calculous biliary disease undergoing endoscopic retrograde cholangiopancreatography (ERCP), but despite this, it is generally believed that gallstones rarely, if ever, cause chronic pancreatitis. The clinical significance and the natural history of the pancreatographic changes seen in patients with gallstone disease is not known. Studies of the pancreatic functions and long-term follow-up of patients with calculous biliary disease, especially those who have abnormal pancreatograms, and the effect of removal of the gallstone on the pancreatographic abnormalities and pancreatic functions are needed to clarify the issue. PMID- 1757736 TI - Developmental potentiality of embryos cultured under low oxygen tension with superoxide dismutase. AB - A low-oxygen culture of preimplantation embryos with superoxide dismutase (SOD) has been demonstrated to produce a marked increase in the blastocyst formation. In this study, we examined the effects of low oxygen-SOD cultures of embryos on the potentiality of embryonic development after intrauterine transplantation and the reproductive ability of the offspring. Mouse pronuclear embryos were cultured in Biggers-Whitten-Whittingham's solution containing 0.3% bovine serum albumin and 500 micrograms/ml SOD under a low-oxygen condition (5% O2, 5% CO2, 90% N2), and 37.2% (110/296) of the embryos developed to blastocysts, with a significant difference from the 1.3% (3/231) under an atmospheric oxygen condition without SOD (P less than 0.01). The blastocysts obtained under a low oxygen-SOD culture condition were transplanted by direct insertion into the uterus of pseudopregnant females 3 days after infertile coitus. The implantation rate was 65.0% (65/100), and the embryo viability rate was 46.0% (46/100). In the control group, in which in vivo developed blastocysts were transplanted into 3-day pseudopregnant females, the implantation rate was 72.5% (81/112), and the embryo viability rate was 51.8% (58/112). The differences between the two groups were not significant. Significant differences also were not observed in either the body weight of pups at birth and 35 days after birth or the mean number of pups delivered by successive mating of the offspring between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757737 TI - Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF ET). AB - The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8% clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P less than 0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P less than 0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical pregnancy. PMID- 1757738 TI - Microbial flora in semen during in vitro fertilization. AB - Semen samples from 183 consecutive unselected men participating in an in vitro fertilization program were retrospectively studied to determine the bacterial and fungal contamination rate before and after antibiotic treatment. To ascertain the influence of semen preparation (wash and swim-up method) on the incidence of microorganisms, semen from 102 male patients was studied before and after swimup. Antimicrobial treatment by prescription of antibiotics decreased the incidence of pathogens by 16.3% (P less than 0.0001). Semen processing was more effective by ridding 57.4% of semen samples of microbial contaminants (P less than 0.0001). When infection of culture media was observed during routine microscopy, all infected oocytes were degenerated, without evidence of fertilization or pronuclei. PMID- 1757739 TI - Intrauterine capsules for incubation of gametes and subsequent release of embryos. AB - In order to obtain incubation in uteri of spermatozoa, oocytes, and embryos, for treatment of patients referred for in vitro fertilization, a capsule was produced which could contain the human gametes and allow human fertilization and embryo growth after intrauterine introduction. Agar was chosen for capsule material and a mold was constructed for the production of capsules. The material was tested in vitro using mouse embryos and human oocytes and sperm. Intrauterine resolution was tested on mice and by insertion on 11 women. Empty capsules were inserted into the uterine cavity in 15 cycles the day after the luteinizing hormone peak and followed by daily ultrasound examinations. The resolution time was adjusted by changing the wall thickness of the capsules. The final type was dissolved after 3 to 4 days. No complications were observed and capsules could be inserted on all occasions. The major problem was expelling of capsules, which occurred in seven cycles. The problem seemed to be solved by the administration of indomethacin at the day of insertion. PMID- 1757740 TI - Intrauterine fertilization capsules--a clinical trial. AB - Treatment of 26 women with tubal infertility was attempted using intrauterine capsules loaded with oocytes and spermatozoa. The stimulation protocol was as used for in vitro fertilization and embryo transfer and consisted of short-term use of Buserelin, human menopausal gonadotropin, and human chorionic gonadotropin. Oocytes were collected by ultrasonically guided transvaginal aspiration, and spermatozoa were prepared by swim-up technique. The gametes were placed in agar capsules 4 hr after oocyte collection, and the capsules were introduced to the uterine fundus using an insertion tube and piston from an intrauterine device. Six complete capsules and parts of two other capsules were expelled. None of the women became pregnant, compared with a pregnancy rate of 21% per aspiration following in vitro fertilization and embryo transfer during the same period. PMID- 1757741 TI - Comparison of unilateral and bilateral tubal transfer in gamete intrafallopian transfer (GIFT). AB - Gamete intrafallopian transfer (GIFT) is traditionally performed by delivering gametes into the ampullary region of either one or two fallopian tubes. The choice is made by the surgeon at the time of laparoscopy based upon the patient's anatomy, the number of oocytes available, and clinical judgment. In this nonrandomized, retrospective review, 399 tubal gamete transfers were performed over a period of 18 months, 133 to a single tube and 266 to both tubes. A clinical pregnancy rate of approximately 24% was observed in each modality. The multiple pregnancy rate of 31.3% for one tube was not significantly different from the 25% seen for two tubes. Unilateral tubal transfer offers the distinct advantages of less gamete and tissue handling. This, along with the apparent same outcome parameters, makes unilateral tubal transfer the preferred method of returning gametes at GIFT. PMID- 1757742 TI - Scanning electron microscope (SEM) study of mouse embryos obtained from isolated blastomeres. AB - Preimplantation diagnosis and embryo sexing offer great possibilities in the prevention of human diseases and in the field of animal production. These techniques involve blastomere isolation. Isolated blastomeres can grow in culture and develop as whole embryos. In this paper we describe, at the scanning electron microscope level, the characteristics of the plasma membrane surface of isolated blastomeres obtained from mouse embryos at the two-cell stage and of embryos grown to the 2/4- and 4/8-cell stages and compare them to control embryos grown in vitro. According to our results the in vitro manipulation of these embryos does not affect the surface characteristics of the plasma membrane in the early cleavage stages. PMID- 1757743 TI - Transvaginal ultrasonic needle-guided aspiration of endometriotic cysts before ovulation induction for in vitro fertilization. AB - Controversy still exists concerning the optimal treatment of endometriomata in endometriosis and its related infertility. Forty-one women with endometriomata who failed to conceive during previous in vitro fertilization and embryo transfer (IVF-ET) cycles (protocol A) were readmitted for ovum pickup following transvaginal ultrasonic needle-guided aspiration of the endometriomata (protocol B). Following aspiration a significantly higher number of oocytes was recovered (P less than 0.0006); subsequently, more embryos were transferred, and significantly higher clinical pregnancy rates per cycle (P less than 0.0001) were achieved. This difference may be directly related to the reduction of extensive ectopic endometrial tissue (endometriomata) with improved ovarian response, follicular accessibility, and, most probably, improved oocyte quality. PMID- 1757744 TI - The effect of chemiluminescent light exposure on the in vitro development of mouse embryos. PMID- 1757745 TI - Bilateral tubal ectopic pregnancy after in vitro fertilization and embryo transfer. PMID- 1757746 TI - Delivered twins from electroejaculation and tubal embryo transfer. PMID- 1757747 TI - Long-term infertility in late-onset 3 beta-ol-dehydrogenase deficiency: successful pregnancy following dexamethasone and in vitro fertilization (IVF) therapy. PMID- 1757748 TI - Successful management and outcome of heterotopic triplet in vitro fertilization (IVF) gestation: twin tubal and surviving intrauterine pregnancy. PMID- 1757749 TI - CD4/immunoglobulin interaction: implications for immune physiology and autoimmunity. AB - CD4 has an important role in T cell activation events that depend on its binding to non-polymorphic MHC class II determinants on antigen-presenting cells. Here, we provide evidence that CD4 also interacts with immunoglobulins (Ig). The Ig binding region lies within residues 21-49 of V1 domain of CD4. Immunochemical studies suggest that this property of CD4 does not depend on the three dimensional folding of the CD4 molecule. Synthetic peptides (p) encompassing amino acid residues 16-49 and 21-49 of CD4 bind immunoglobulins in comparable way to the intact molecule. In vitro p 16-49 enhances significantly idiotype/anti idiotype and some weak antigen-antibody interactions. Antigen antibody complexes formed in antigen excess bind CD4 peptides with much higher avidity then non complexed antibodies. The possible role of the CD4/Ig interaction in T-B cell cooperation is discussed. PMID- 1757750 TI - MDA-image: an environment of networked desktop computers for teleradiology/pathology. AB - MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation. PMID- 1757752 TI - A very large PC LAN as the basis for a hospital information system. AB - Brigham and Women's Hospital is converting its financial, administrative and clinical information systems from a mini-computer environment to a platform based on MUMPS and a network of several thousand personal computers. This article describes the project rationale and status and provides an overview of the architecture of the new system. The initial results of the project indicate that the personal computer network can provide large amounts of processor power and storage at costs per unit of power and storage that are several times less expensive than the minicomputer environment. The performance of the converted Accounts Payable system indicates that the architecture can deliver acceptable performance. PMID- 1757751 TI - Significant efficiency findings while controlling for the frequent confounders of CAI research in the PlanAlyzer project's computer-based, self-paced, case-based programs in anemia and chest pain diagnosis. AB - Richard E. Clark in his widely published comprehensive studies and meta-analyses of the literature on computer assisted instruction (CAI) has decried the lack of carefully controlled research, challenging almost every study which shows the computer-based intervention to result in significant post-test proficiency gains over a non-computer-based intervention. We report on a randomized study in a medical school setting where the usual confounders found by Clark to plague most research, were carefully controlled. PlanAlyzer is a microcomputer-based, self paced, case-based, event-driven system for medical education which was developed and used in carefully controlled trials in a second year medical school curriculum to test the hypothesis that students with access to the interactive programs could integrate their didactic knowledge more effectively and/or efficiently than with access only to traditional textual "nonintelligent" materials. PlanAlyzer presents cases, elicits and critiques a student's approach to the diagnosis of two common medical disorders: anemias and chest pain. PlanAlyzer uses text, hypertext, images and critiquing theory. Students were randomized, one half becoming the experimental group who received the interactive PlanAlyzer cases in anemia, the other half becoming the controls who received the exact same content material in a text format. Later in each year there was a crossover, the controls becoming the experimentals for a similar intervention with the cardiology PlanAlyzer cases. Preliminary results at the end of the first two full trials shows that the programs have achieved most of the proposed instructional objectives, plus some significant efficiency and economy gains. 96 faculty hours of classroom time were saved by using PlanAlyzer in their place, while maintaining high student achievement. In terms of student proficiency and efficiency, the 328 students in the trials over two years were able to accomplish the project's instructional objectives, and the experimentals accomplished this in 43% less time than the controls, achieving the same level of mastery. However, in spite of these significant efficiency findings, there have been no significant proficiency differences (as measured by current factual and higher order multiple choice post-tests) between the experimental and control groups. Very careful controls were used to avoid what Clark has found to be the most common confounders of CAI research. Accordingly, this research proved Clark's rival hypothesis, that the computer, in itself, does not appear to contribute to proficiency gains, at least as measured by our limited post-testing. Clark's position is that the computer is primarily a vehicle--as is either a pill or a hypodermic needle for delivering a drug.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1757753 TI - The use of graphic design in an interactive computer teaching program. AB - The widespread diffusion of affordable computers into the scientific and educational community has provided the opportunity to design medical and scientific teaching programs illustrated either by hand or by utilizing commercially available software and manipulating existing computer generated images. The medical illustrator can provide the ideal aesthetic link between text format information and the visual representation of such knowledge in a concise presentation format. The availability of interactive multimedia programs has given the medical illustrator an environment to create and enhance Hypermedia designed specifically for the purpose of medical education. This paper will focus on the incorporation of illustration and screen design into "CT The Game," an experimental medical teaching program currently being developed in the Johns Hopkins Body CT Imaging Laboratory. The program is designed to provide an enjoyable approach to learning Computed Tomography (CT), and is directed toward an audience of medical students, residents, and fellows. PMID- 1757754 TI - An inventory model for optimizing purchasing of intravenous fluids for hospitals: a case study. AB - This paper deals with determining the optimal level of purchase of intravenous fluids for hospitals by utilizing inventory control concepts. Using the conceptual framework of the economic order quantity (EOQ) model, the hospital administrators can elicit the efficient materials management, thus reducing both the space and capital requirements without compromising the quality of services rendered. PMID- 1757755 TI - Quality assurance tracking or "finding the needle in a haystack". AB - This paper will present a picture of the steps required from conception, through development, and leading to implementation of an automated Quality Assurance Incident Tracking System within in a multihospital system utilizing general purpose software (WordPerfect and Lotus Agenda). This automated tracking system provides the manager with an effective and efficient method to control multiple staff assignments, tasks, and manage multiple objectives over the resolution cycle associated with hospital incident reporting in the Quality Assurance arena. It also provides the QA managers and hospital executives with an individualized record of the Incident's progress and helps identify useful and dysfunctional patterns in the resolution of the Incident. The identification of these patterns can assist hospital management in revising and developing protocols and procedures that minimize hospital exposure to state sanctions and provide a mechanism to improve the quality of care in the institution: QA Tracking, Quality Assurance, Incident, Automated Tracking. PMID- 1757756 TI - Should we be screening for early diabetic renal disease? PMID- 1757757 TI - The measurement of morbidity in general practice. AB - (1) The need for morbidity data based on general practice arises because: (a) the consultation in general practice is the entry point into the health care system; (b) among the health problems brought to the attention of doctors, most are dealt with completely in general practice; (c) general practice records can provide a comprehensive database for health care. (2) The routine measurement of morbidity has to be based on "working diagnostic terms" derived by consensus amongst recorders because: (a) many episodes of illness involve only one consultation and the doctor is required to make the most of the information available to him at the time; (b) the specification of criteria would require validating evidence of conformity and this is not a realistic option on a wide scale; (c) health care data which include the opinion of the general practitioner are more valuable than data based on patient perceptions of illness. (3) The analysis and interpretation of data from general practice: (a) should preferably be based on persons as the unit of analysis; (b) when based on consultations, may be useful for examining workload, but has limited epidemiological value; (c) can, by person linkage, facilitate the study of disease concurrence; and (d) is essential for managing the health care system and monitoring the public health. PMID- 1757758 TI - Chronic leg ulcers: an underestimated problem in primary health care among elderly patients. AB - STUDY OBJECTIVE: The aim was to establish leg ulcer point prevalence, basal patient characteristics, and level of caretaking. DESIGN: The study was a postal cross sectional survey. The validity was ensured by examining a randomly selected sample of reported patients. Responding health care officials were asked to report all patients with an open wound below knee (including foot ulcer) which did not heal or was supposed to heal within a six week period after onset of ulceration. Response rate was 92%. SETTING: Inpatient and outpatient care in hospitals, community health care, and private nursing homes within Skaraborg county, with a population of 270,800. PARTICIPANTS: 827 individual patients were found with active leg ulcers, 526 women and 301 men. MEASUREMENTS AND MAIN RESULTS: Age adjusted sex ratio of ulcer patients was 1:1.4 (M:F). The median age was 78 years for women and 76 for men; 700 patients (85%) were older than 64 years. The point prevalence for active leg ulcers was 3.0/1000 total population. District nurses provided care for 680 patients (82%), 106 (13%) were in hospital care, and 41 (5%) were managed by outpatient departments. CONCLUSIONS: There has been an underestimation of the leg ulcer problem among elderly patients, especially men. With an expected increasing number of elderly people it is important that this problem is recognised and measures taken to improve the primary care of these patients. PMID- 1757759 TI - Quantifying health aspects of passive smoking in British children aged 5-11 years. AB - STUDY OBJECTIVE: The aim was to estimate the dose-response relations of height and respiratory symptoms to passive smoking in children aged 5-11 years. DESIGN: The study was an analysis of existing observational studies, comprising three samples: English representative; English inner city; Scottish representative. SETTING: Primary schools (children aged 5-11 years). PARTICIPANTS: The study population included 5002 English children from the representative sample (69.1% of total eligible), 2903 English inner city children (42.0%), and 3319 representative Scottish children (75.6%). MEASUREMENTS AND MAIN RESULTS: No significant relation was found between child's height and total parental smoking in the home. Relative risk for persistent wheeze on exposure to 20 cigarettes per day was 1.35, compared to no exposure. Risk of at least one respiratory condition attributable to passive smoking reached 8.1% in white English inner city children. CONCLUSIONS: The relation of child's height to passive smoking was not substantiated. The risk of respiratory conditions resulting from passive smoking, although small, is not negligible. PMID- 1757760 TI - Association of age and social class with suicide among men in Great Britain. AB - STUDY OBJECTIVE: The aim was to investigate suicide and "undetermined" deaths by age, economic activity status, and social class in Great Britain among males of working age. DESIGN: The study was a cross sectional analysis of Registrar General's data for England and Wales around 1981, repeated for around 1971, and for Scotland around 1971 and 1981. MEASUREMENTS AND MAIN RESULTS: For England and Wales around 1971, suicide and undetermined death rates showed a progressive increase with age and a markedly higher rate in the lower social classes. A significant interaction effect was identified in the central age groups of the lower occupational categories. This interaction was confirmed in the remaining three data sets, notwithstanding some differences in the profile of age specific mortality. Other findings included a higher standardised mortality ratio for the economically inactive, who also showed an earlier peak in age specific mortality, and a relative concentration of undetermined as compared to suicide deaths in the lower social classes, but not all these further results were fully replicated. CONCLUSIONS: There is a concentration of suicide and undetermined deaths in the middle age groups of the lower social classes. Plausible explanations include both the social drift and the social genesis hypotheses, the latter including the effects of long term unemployment. PMID- 1757761 TI - Mortality from dementia among gastroduodenal ulcer patients. AB - STUDY OBJECTIVE: The aim was to examine whether a high intake of aluminium containing antacids is a risk for Alzheimer's disease. DESIGN: The mortality from dementia (1970-87), coded from death certificates as underlying or contributory cause of death, was compared with national rates in a cohort of patients who had surgery for gastroduodenal ulcer disease between 1911 and 1978. SETTING: Patient data were obtained from patient records from major hospitals in western Norway. PARTICIPANTS: 4179 patients were identified who met the study criteria, which included having had a documented stomach operation, having a reliably identifiable personal number, and being alive on Jan 1, 1970. MEASUREMENTS AND MAIN RESULTS: The standardised mortality ratio for dementia was 1.10 (95% CI 0.85 1.40, n = 64) for all patients, while for patients operated on in the period 1967 78 it was 1.25 (95% CI 0.66-2.13, n = 13). CONCLUSIONS: As the majority of patients operated on after 1963 have probably been heavy consumers of aluminium containing antacids, the study provides meager evidence that a high intake of aluminium is an important risk factor for Alzheimer's disease, the major cause of dementia. However, the possibility of a raised mortality from Alzheimer's disease cannot be ruled out due to probable misclassification both in diagnosis and exposure. In addition, the observation period may have been too short to detect an effect since the latent period for Alzheimer's disease may be very long. PMID- 1757762 TI - Low birthweight, preterm, and small for gestational age babies in Scotland, 1981 1984. AB - STUDY OBJECTIVE: The aim was to examine the effect of maternal age, gravidity, marital status, previous perinatal deaths, and parental social class on babies born low birthweight, preterm, and small for gestational age. DESIGN: The study used data on discharge summaries from all maternity hospitals in Scotland. SETTING: The study was based on all singleton deliveries in Scotland. PARTICIPANTS: The analysis involved information on 259,462 singleton babies born during the four years 1981-84 in Scotland. MEASUREMENTS AND MAIN RESULTS: Previous perinatal death was found to be the strongest predictor for both preterm and low birthweight. Single mothers were at particularly high risk of having a small for gestational age baby and those who were previously married of having a preterm baby. Women aged less than 20 years old, those over 34 years old, nulligravidae, and those of parity 3 or more were also at increased risk of adverse pregnancy outcome. Mothers and fathers in manual social classes and those who could not be assigned a social class on the basis of their occupation were at increased risk for all three adverse outcomes studied. The babies of parents who were in manual occupations were twice as likely as those of parents in non-manual occupations to be small for gestational age and almost twice as likely to be low birthweight. CONCLUSIONS: Mother's social class is a risk factor for adverse pregnancy outcome independent of maternal age, parity, and adverse reproductive history, and also independent of father's social class. Information on both parents' occupations should be collected in maternity discharge systems. PMID- 1757763 TI - An indicator of adverse pregnancy outcome in France: not receiving maternity benefits. AB - STUDY OBJECTIVE: The aim was to compare the social characteristics, the pregnancy outcome, and the antenatal care of women in France who did not receive maternity benefits to women who did. These benefits (860 FF, approx 86 pounds per month) are given to every pregnant woman, starting in the second trimester. Payments are made on the condition that at least three antenatal visits are made, the first being before the end of the first trimester. DESIGN: The study involved a random sample of women who were interviewed after delivery during their stay in hospital. Data on pregnancy outcome were collected from medical records. SETTING: The study was carried out in four public maternity units in different regions of France. PARTICIPANTS: 1692 women were included in the analysis (86.8% of the selected sample). Of 257 exclusions, 40 had multiple pregnancies, 189 had missing data, and 28 did not answer the question concerning maternity benefits. MEASUREMENTS AND MAIN RESULTS: 4.3% of the women did not receive any maternity benefits. These women lived in poorer social conditions than the women who received the benefits. They had a higher preterm delivery rate, after controlling for risk factors in a logistic regression. Women without maternity benefits were characterised by a lower level of care, yet the majority began their antenatal care during the first trimester or had more than six visits. CONCLUSIONS: Not receiving maternity benefits during pregnancy is an index of an underprivileged situation and a risk factor for pregnancy outcome. PMID- 1757764 TI - Socioeconomic differences in cancer survival. AB - STUDY OBJECTIVE: The aim was to investigate the relationship between socioeconomic status and cancer survival. DESIGN: This was a prospective study, linking census and vital registration records for an approximate 1% representative sample of those enumerated in England and Wales in the 1971 census. SETTING: The study population is nationwide. PARTICIPANTS: The study sample consists of 250,588 men and 262,484 women. During 1971-81, 17,844 cases of cancer were registered, and of those registered, 13,532 died during 1971-1983. MEASUREMENTS AND MAIN RESULTS: Socioeconomic status was assessed in terms of housing tenure. Council tenants, the low socioeconomic group, had poorer survival than owner occupiers, the high socioeconomic group, for the combined group of all neoplasms, and for 11 out of 13 neoplasms examined in males, and 12 out of 15 neoplasms examined in females. Differences were found irrespective of age, cause of death and prognosis of the cancer. Survival analysis by length of follow up indicated that council tenants were more likely to present at a later stage than owner occupiers. CONCLUSIONS: Wide survival differentials were observed between socioeconomic groups. Differences in survival for cancers of poor prognosis (eg, oesophagus, pancreas, lung) where treatment has little effect, cannot be attributed to socioeconomic differences in treatment. The survival differences for cancers of good prognosis (eg, corpus uteri, bladder, skin) could, in part, be due to differences in treatment. It is probable that delay in seeking care is one of the major contributing causes. PMID- 1757765 TI - The cost of screening for colorectal cancer. AB - STUDY OBJECTIVE: The aim was to make projections of the likely costs and yield resulting from the implementation of a faecal occult blood screening programme for colorectal cancer. DESIGN: Cost and clinical data were derived from the MRC colorectal screening trial currently in progress in Nottingham, UK. SETTING: The above data were used as the basis for modelling the likely implications were the trial to be reproduced as a screening programme within a "typical" family practitioner committee area. MAIN RESULTS: For an average family practitioner committee area with a target population of 75,000 subjects aged 50-74 years, the initial screening round might be expected to detect 85 cancers at a total cost of approximately 250,000 pounds. This represents a cost per cancer detected of 2700 pounds and a cost per person screened of approximately 5 pounds. For subsequent screening rounds, total costs might be expected to fall although average costs are likely to remain approximately constant. CONCLUSIONS: The model is successful in generating "order of magnitude" estimates for the costs of implementation of a screening programme for colorectal cancer. As benefit estimates are not yet available, however, no cost-effectiveness analysis can be undertaken at this stage. In general, sensitivity analyses reveal that programme costs are more sensitive to changes in clinical variables, especially detection and compliance rates, than they are to variations in the costs of resource inputs. A screening programme with a more elaborate protocol than that currently employed in the Nottingham trial will entail considerable cost increases. PMID- 1757766 TI - Influence of "diagnostic delay" upon cancer survival: an analysis of five tumour sites. AB - STUDY OBJECTIVE: The aim was to assess the relationship between survival, tumour stage, and the interval from first symptom to diagnosis (SDI, or duration of symptoms). DESIGN: This was a retrospective follow up study of a cohort of patients registered in the tumour registry of the Hospital del Mar (Barcelona). SETTING: Hospital based tumour registry, with patients derived mainly from the City of Barcelona. PARTICIPANTS: 1247 cases of lung, breast, stomach, colon, or rectal cancer were analysed using survival curves and Cox proportional hazards regression. Subjects (mean age 63.6 years) were followed for a median length of 12.9 months after diagnosis. At the time of diagnosis one fourth of patients had disseminated disease. MEASUREMENTS AND MAIN RESULTS: Based on clinical records, a physician registered the onset time of the first symptom attributable to cancer (from which the SDI is computed), as well as the tumour stage at diagnosis. Other measurements followed standard tumour registry procedures. Overall, the crude mean SDI was 5.15 months (SD 8.03, median 2.03); only 24.5% of cases had an SDI less than a month. Crude mean SDIs by anatomical site were as follows: lung cancer 3.07 months; breast 7.44; stomach 5.34; colon 5.74; rectum 5.03. Tumour extension did not appear to be significantly influenced by SDI, only breast cancer showing a distinct pattern of increased extension with increasing SDI. As expected, the probability of survival decreased monotonically with increasing stage in all sites. Tumour site was also a significant predictor of survival, which at one year ranged from 93% for breast cancer to 28% for lung cancer. However, a longer SDI tended sometimes to be associated with a better chance of survival, a fact that was most apparent in colon cancer. All Cox proportional hazards models showed a consistent picture: SDI was not a significant predictor of survival (age and sex adjusted hazard ratios ranging from 0.97 to 1.01), neither was sex; age did predict survival, and so did site and stage. CONCLUSIONS: The results provide further evidence of a very weak relationship between SDI and tumour stage at diagnosis (except for breast cancer), and between SDI and survival, thus emphasising some limitations within which early clinical detection operates. They also suggest that in addition to reflecting patient and physician behaviour, as well as the functioning of the health system, SDI may be influenced by the biological behaviour of the tumour. PMID- 1757767 TI - Cultural and economic determinants of geographical mortality patterns in The Netherlands. AB - STUDY OBJECTIVE: The geographical pattern of mortality in The Netherlands is dominated by an area of relatively high mortality in the southern part of the country. The aim was to analyse the background of this geographical mortality pattern in the early 1980s, and its evolution over time since the early 1950s. DESIGN: Mortality data by district (n = 39), cause of death (13 large causes, "symptoms and ill defined conditions", all other causes), and time period (1950 54, 1960-64, 1970-74, 1980-84) were available from the Netherlands Central Bureau of Statistics. Standardised mortality ratios were calculated, and the logarithms of these were related to three sociodemographic characteristics using multiple, ordinary least squares regression analysis. SETTING: This study used data for the whole Dutch population. MAIN RESULTS: Although the geographical mortality pattern has been rather stable over the last decades, a clear tendency towards convergence is also apparent. Approximately 90% of the current excess mortality in the southern part of the country is due to cardiovascular diseases. The results of regression analysis show that the excess mortality is primarily related to the high percentage of Roman Catholics in this part of the country, and additionally to a slightly lower average income. In The Netherlands, a higher percentage of Roman Catholics in the population is linked with higher all cause mortality rates, as well as with higher mortality rates for lung cancer, ischaemic heart disease, cerebrovascular disease, arterial disease, and chronic non-specific lung disease. Survey data show that these associations are partly due to a higher prevalence of smoking among Roman Catholics. As in many other countries, a lower average income is linked with high all cause mortality rates in The Netherlands. Cause specific data show negative associations for stomach cancer, ischaemic heart disease, cerebrovascular disease, chronic non-specific lung disease, and traffic accidents. Since the early 1950s the association between geographical mortality patterns and the percentage of Roman Catholics in the population has gradually become less strongly positive. This suggests that the convergence of the mortality rates in the South towards the national average may be related to a gradual lessening of differences in lifestyle between population groups. CONCLUSIONS: Both cultural and economic factors are important in the explanation of geographical mortality patterns in The Netherlands. PMID- 1757768 TI - Value of mortality data and necropsy records in monitoring morbidity in a population. AB - STUDY OBJECTIVE: The aim was to compare the value of four sources of data in assessing morbidity in a population: (1) data from a screening programme including follow up records, (2) death certifications by attending physicians, (3) death certifications by doctor-coroners, and (4) necropsy reports. DESIGN: The study was a cohort analysis of health and mortality in a sample of agricultural workers first examined in 1964-66 when they were aged 60 years or older. Follow up examinations enabled morbidity assessment to be made and ICD diagnostic categories to be compared with data available on persons in the cohort who had died. SETTING: Hajduszoboszlo, a small town in eastern Hungary. PARTICIPANTS: 1412 persons (96.1% of those aged greater than or equal to 60 years) were examined in 1964-6. Those still alive and available in 1989 were examined again. Necropsy records were available for 144 persons from the cohort in 1989 and were extensively reviewed in comparison with data available from other sources. MEASUREMENTS AND MAIN RESULTS: Comparison of causes of death established at necropsy showed marked differences from those registered by attending physicians and doctor-coroners, deviations ranging from -91.6% to +74.8%; 19.4% of underlying causes of death occurred exclusively in the necropsy group. Major divergencies in diagnostic classification occurred in the three data sources, particularly for diseases of the circulatory system, where hypertensive renal disease, old myocardial infarction, acute cerebrovascular disease, and venous thrombosis were rarely documented by physicians/coroners. When necropsy data were used the number of diagnostic categories increased strikingly over the other sources of information. Necropsy records revealed quantitatively similar information on morbidity to follow up examination though there were qualitative differences, necropsy being less likely to document diagnoses of endocrine disorders, mental and neurological diseases, digestive disorders, and musculosketal disorders. CONCLUSIONS: Necropsy records contain much valuable material not available from other sources, exceeding by ninefold the amount of information reported at present. A way should be found to make use of this large data pool. PMID- 1757769 TI - Housing and appendicitis in Anglesey. AB - STUDY OBJECTIVE: The aim was to test the hypothesis that provision of household amenities such as domestic hot water systems and bathrooms changed hygiene which thereby triggered the epidemic of appendicitis in Anglesey after the second world war. DESIGN: The study was a cross sectional survey with histories of housing and appendicectomy obtained from Anglesey residents by postal questionnaire. The main outcome measure was reported appendicectomy. SETTING: Four general practices in Anglesey. SUBJECTS: 2531 men and women born during 1923-62 and randomly selected from age-sex registers. Overall response rate was 73.7%. MAIN RESULTS: Subjects born into households with amenities--piped water, hot water systems, and bathrooms had, if anything, a reduced risk of appendicectomy. However, those who subsequently moved to houses that lacked amenities were at significantly higher risk than people born into houses without amenities who later acquired them. CONCLUSIONS: Provision of household amenities was not the important trigger to the epidemic of appendicitis which occurred in Anglesey after the second world war. Rather, the trigger may have been reduction in domestic crowding caused by the falling birth rate. Findings among those who moved house support other evidence that after infancy household amenities protect against appendicitis and contributed to the fall in appendicitis rates in Anglesey after 1965. PMID- 1757770 TI - The food pattern in geographical relation to the risk of multiple sclerosis in the Mediterranean and Near East region. PMID- 1757771 TI - An identifiable molluscan neuron responds to changes in earth-strength magnetic fields. AB - Diverse animals can orient using geomagnetic cues, but little is known about the neurophysiological mechanisms that underlie magnetic field detection. The marine mollusc Tritonia diomedea (Bergh) has a magnetic sense and its nervous system is amenable to cellular-level electrophysiological analysis. In a semi-intact whole animal preparation, intracellular recordings from the large, visually identifiable neurons left pedal 5 (LPe5) and right pedal 5 (RPe5) in the brain of Tritonia revealed enhanced electrical activity in response to changes in ambient earth-strength magnetic fields. No such changes in activity were observed in approximately 50 other neurons subjected to identical magnetic stimuli. The responses of LPe5 were characterized by increases in spiking frequency occurring about 6-16 min after the ambient magnetic field had been rotated to a new position. The response was abolished when the brain had been isolated from the periphery of the animal by severing nerves, a procedure that also transected prominent neurites of LPe5. We hypothesize that LPe5 is one component of a neural circuit mediating detection of the earth's magnetic field or orientation to it. PMID- 1757772 TI - Activities of key metabolic enzymes in the heater organs of scombroid fishes. AB - Maximal in vitro activities of key metabolic enzymes were measured in brain and eye heaters of five species of scombroid fishes. Istiophorid billfishes (blue marlin, striped marlin and Mediterranean spearfish), xiphiid billfishes (Pacific and Mediterranean stocks) and a scombrid fish (butterfly mackerel) were included in the analysis. Our main objectives were (1) to assess the maximum possible substrate flux in heater tissue, and (2) to determine what metabolic substrates could fuel heat production. Heater tissue of all scombroids examined showed extremely high oxidative capacity. Activities of citrate synthase, a commonly measured index of oxidative metabolism, included the highest value ever reported for vertebrate tissue. In most billfishes, citrate synthase activities were similar to or higher than those found for mammalian cardiac and avian flight muscle. Marker enzymes for aerobic carbohydrate metabolism (hexokinase) and fatty acid metabolism (carnitine palmitoyltransferase and 3-hydroxyacyl-CoA dehydrogenase) also displayed extraordinarily high activities. Activities of carnitine palmitoyltransferase measured in heater organs were among the highest reported for vertebrates. These results indicate that heat production could be fueled aerobically by either lipid or carbohydrate metabolism. Inter- and intraspecifically, heater organs of fishes from the colder Mediterranean waters had a higher aerobic capacity and, hence, a greater heat-generating potential, than fishes from the warmer waters of the Pacific. This difference may be attributed to different thermal environments or it may result from allometry, since fishes caught in the Mediterranean were considerably smaller than those caught in the Pacific. PMID- 1757773 TI - The dopamine and 5-hydroxytryptamine content of locust and cockroach salivary neurones. AB - The salivary glands of the cockroach and locust are innervated primarily from two pairs of motoneurones, designated SN1 and SN2, in the suboesophageal ganglion. Intracellular cobalt fills and subsequent silver intensification were used to reveal the morphology of these cells in both species. Fluorescent microscopy, following treatment of the ganglion with glyoxylic acid, showed that in both species only the SN1 neurones contained catecholamines. A radioenzymatic assay for dopamine, performed on the locust SN1 neurones, confirmed that this catecholamine was present. A radioenzymatic assay for 5-hydroxytryptamine (5-HT), performed on both pairs of salivary neurones in the locust, revealed small quantities of this amine in the SN2 neurones, but no significant amount in the SN1 neurones. In the cockroach, 5-HT was assayed in the SN2 neurones only. In contrast to the locust, however, the 5-HT content of these cells was not significantly above that of control cells taken from other ganglia. These observations demonstrate that only the SN1 neurones are the source of the catecholaminergic fibres investing the locust and cockroach salivary glands. The difference in neurotransmitter content between the SN1 and SN2 neurones suggests that these neurones have separate functions in the control of salivary secretion. PMID- 1757774 TI - Intracellular pH in the toad Bufo marinus following hypercapnia. AB - We investigated the effects of hypercapnia on intracellular acid-base regulation in brain and liver of the toad Bufo marinus L. After 1 h at 5% CO2, arterial PCO2 increased significantly, from 1.6 +/- 0.04 to 5.7 +/- 0.23 kPa, while brain and liver intracellular pH (pHi) decreased significantly. Reductions in pHi of both tissues were partially compensated by increased levels of bicarbonate. Surprisingly, however, compensation was lower than expected in brain and higher than expected in liver. We suggest that compensation in brain may be limited by secondary effects of bicarbonate loading in this tissue. PMID- 1757775 TI - How stimulus direction determines the trajectory of the Mauthner-initiated escape response in a teleost fish. AB - Fishes use the Mauthner-initiated C-start for short-latency evasion of predators. C-starts consist of a sudden turn (stage 1) and a rapid acceleration (stage 2). We analyzed high-speed cine films of goldfish C-starts elicited by dropping a ball into the water. It was previously thought that stage 1 angle does not vary concomitantly with the angle of the threatening stimulus relative to the position of the fish. We found, however, a significant inverse relationship between the direction of the impact of the ball and the angle turned by the end of stage 1. When starting near a wall, or when its usual trajectory was blocked by a wall, the fish used an escape route that was not predictable from the stimulus angle. The fish did not appear to correct its trajectory if it began to turn towards the ball. This behavioral evidence supports the previous notion that the underlying neural command is ballistic and does not use sensory information from the stimulus once the movement begins. If this is so, the fish probably utilizes information on obstacle location in the interval leading up to the trigger stimulus. PMID- 1757776 TI - The role of blood glucose in the restoration of muscle glycogen during recovery from exhaustive exercise in rainbow trout (Oncorhynchus mykiss) and winter flounder (Pseudopleuronectes americanus). AB - The role of blood-borne glucose in the restoration of white muscle glycogen following exhaustive exercise in the active, pelagic rainbow trout (Oncorhynchus mykiss) and the more sluggish, benthic winter flounder (Pseudopleuronectes americanus) were examined. During recovery from exhaustive exercise, the animals were injected with a bolus of universally labelled [14C]glucose via dorsal aortic (trout) or caudal artery (flounder) catheters. The bulk of the injected label (50 70%) remained as glucose in the extracellular fluid in both species. The major metabolic fates of the injected glucose were oxidation to CO2 (6-8%) and production of lactate (6-8%), the latter indicative of continued anaerobic metabolism post-exercise. Oxidation of labelled glucose could account for up to 40% and 15% of the post-exercise MO2 in trout and flounder, respectively. Exhaustive exercise resulted in a reduction of muscle glycogen stores and accumulation of muscle lactate. Glycogen restoration in trout began 2-4h after exercise, whereas in flounder, glycogen restoration began within 2h. Despite a significant labelling of the intramuscular glucose pool, less than 1% of the infused labelled glucose was incorporated into muscle glycogen. This suggests that blood-borne glucose does not contribute significantly to the restoration of muscle glycogen following exhaustive exercise in either trout or flounder and provides further evidence against a prominent role for the Cori cycle in these species. PMID- 1757777 TI - The action of acetylcholine on the locomotor central pattern generator for swimming in Xenopus embryos. PMID- 1757778 TI - The relationship between body mass and ventilation rate in mammals. PMID- 1757779 TI - Double-focal videomicroscopy: a simple video system for analyzing the dynamics of cell motility. PMID- 1757780 TI - Presleep suggestion related to a phobic object: successful manipulation of reported dream affect. AB - Twenty-four female subjects with a strong dislike of snakes slept for four nonconsecutive nights in the laboratory. They were divided into four groups of six, each group receiving a different presleep suggestion on Nights 3 and 4. On Nights 2, 3, and 4, before sleep, the subjects saw but did not have to touch a live snake and their dreams were collected for each REM period. The results showed that, when compared with the subjects who received the negative affect suggestions, subjects who received positive affect suggestions had significantly higher levels of positive emotions in their dreams, rated their own dreams as more pleasant, and had significantly lower levels of anxiety, sadness, and aggression. These results support the hypothesis that presleep suggestion can be an effective technique in influencing the affective dimension of the dream. PMID- 1757781 TI - The relationship between trauma and financial and physical well-being among Cambodians in the United States. AB - This study focused on the relationship between trauma and financial and physical well-being of Cambodian refugees in the United States. Trauma was defined by three variables: whether or not trauma had been experienced in Cambodia, the number of traumas experienced, and the number of years spent in refugee camps. It was hypothesized that these trauma variables would predict financial and physical health among Cambodians in the United States. A discriminant analysis showed significant relationships between the trauma variables and current employment status, and multiple regression analyses showed that trauma predicted income and physical health. PMID- 1757782 TI - Motion thresholds in infants to sinusoidal gratings. AB - Motion thresholds were determined at 9 degrees eccentricity in infants (mean = 14 weeks old). The stimuli used were computer-generated sinusoidal gratings presented through a 7.45 degrees aperture at a contrast ratio of .83. The range of velocities (.5, 1, 2, 4, and 6 degrees per s) was examined at only one spatial frequency (1 cycle per degree). At low velocities (less than 2 degrees per s), the infants showed no clear preference for the moving stimulus over the stationary stimulus. At faster velocities (2-6 degrees per s), the infants exhibited a clear preference for the moving stimulus. The results were interpreted as indicating that infants at 3 months of age are relatively insensitive to slow motions for low spatial frequency stimuli. PMID- 1757783 TI - Recovery of susceptibility following audiogenic seizure in mice. AB - The rate at which SJL/J mice recover susceptibility following an initial sound induced seizure was examined. Fewer than 15% of the subjects seized when retested after a 2-min delay, and only 50% reseized after a 10-min delay. The likelihood of a second seizure was enhanced if the initial seizure exhibited a rapid progression to clonus. During the retest, seizures progressed more slowly than during the initial test, which indicates that recovery was not complete even if a second seizure was induced. Finally, recovery of seizure susceptibility was prevented as long as the subject continued to be exposed to intense auditory stimulation following the initial convulsion, an effect previously noted by Alexander and Kopeloff (1980). The findings are discussed in terms of a recently proposed central inhibitory model of the recovery of audiogenic seizure susceptibility. PMID- 1757784 TI - Factor structure of temperament in the third year of life. AB - The hypothesis that the nine dimensions of temperament defined by Chess and Thomas (1984) would emerge in a principal components analysis of maternal descriptions of 763 two-year-olds in a longitudinal study was not confirmed. The only component that bore any resemblance to the a priori dimensions of temperament proposed by Chess and Thomas was the sixth component--defining rhythmicity--in a Promax rotation. A higher order rotation to a two-factor solution produced components representing sociability and difficult behavior, respectively. It is argued that in the long term, these dimensions of temperament will, through the process of interaction with others, provide dimensions of personality identified by Hans Eysenck and his colleagues (1985). PMID- 1757785 TI - Protection against cadmium toxicity in yeast by alcohol dehydrogenase. AB - A cDNA expression library from Schizosaccharomyces pombe was transformed into Saccharomyces cerevisiae to screen for genes capable of conferring cadmium resistance to S. cerevisiae cells. The cDNA library was cloned into the S. cerevisiae expression vector pDB20 which is designed to express cDNAs via the constitutively-expressed promoter of the gene for alcohol dehydrogenase I (ADH1). Terminator and polyadenylation signals are also provided by the ADH1 gene. Cadmium resistant colonies were shown to arise by a recombination event leading to the exchange of the S. pombe DNA with the chromosomal ADH1 gene and a consequent dramatic increase in the ADH1 gene expression due to the high copy number of the plasmid. The overexpression of ADH1 effectively buffered the cells for cadmium ions by formation of Cd-ADH. PMID- 1757786 TI - Copper in biological systems. A report from the 6th Manziana Conference, September 23-27, 1990. AB - Enzymes and proteins: AO, amine oxidase; and as proposed in reference 3, BSAO, bovine serum AO; SSAO, swine serum AO; SKDAO, swine kidney AO; PSAO, pea seedling AO; APAO, arthrobacter P1AO; MADH, methylamine dehydrogenase; AAO, ascorbic acid oxidase; alpha-AE, alpha-amidating enzyme; Az, azurin; COX, cytochrome c oxidase; CP, ceruloplasmin; DBH, dopamine beta-hydroxylase; GO, galactose oxidase; Hc, hemocyanin; MT, metallotheonein; NIR, nitrite reductase; SOD, superoxide dismutase. Cofactors: Dopa, 3,4 dihydroxyphenylalanine; Topa, 3,4,6 trihydroxyphenyl-alanine; PLP, pyridoxal-phosphate; PQQ, pyrroloquinolinequinone. Reagents: DDC, diethyldithiocarbamate; DMG, diaminoguanidine; DMSA, dimercaptosuccinic acid; NTA, nitrilotriacetic acid. Technique-related: XANES, x ray absorption near edge spectroscopy; EXAFS, extended x-ray absorption fine structure; ENDOR, electron-nuclear double resonance; ESEEM, electron spin echo envelope modulation; CD, circular dichroism; MCD, magnetic circular dichroism; NMRD, nuclear magnetic resonance dispersion; nqi, nuclear quadrupole interaction; DSC, differential scanning calorimetry. PMID- 1757787 TI - The effect of trithiomolybdate and some selenium compounds upon 109Cd labeled rat metallothionein in vitro: the possibilities for cadmium chelation therapy. AB - The main binding protein for 109Cd was metallothionein after in vitro incubation of various tissue cytosol preparations obtained from rats supplemented with zinc. The exception was heart cytosol where the label was associated with higher molecular weight proteins. The metallothionein-bound 109Cd was sensitive to trithiomolybdate and moved too higher molecular weight proteins, presumably because of the creation of new stronger ligands by the association of thiomolybdate with these proteins. The 109Cd binding was affected by selenate, selenite, and selenide while molybdate, sulphate, and thiosulphate were ineffective. It is proposed that thiomolybdates should be investigated for use in the therapy of in vivo cadmium toxicity because they can remove the accumulated metal from metallothionein. PMID- 1757788 TI - Astrogliosis in von Economo's and postencephalitic Parkinson's diseases supports probable viral etiology. AB - A marked generalized astrogliosis was observed in the frontal and temporal white matter from a case of von Economo's disease and another of postencephalitic Parkinson's disease, which areas were otherwise devoid of any other demonstrable microscopic lesions. No similar astrocytic reaction of any severity was observed in the same areas in a number of other brain diseases or controls, except when other kinds of lesions were present in the same section, with reactive astrocytes being present within the primary or defining lesion or immediately close by. The marked astrogliosis in von Economo's and postencephalitic Parkinson's diseases in areas "distant" from the primary lesions seeming to indicate extensive pathological involvement, added to the strong qualitative and quantitative similarity of this reaction to that observed in concurrently studied cases of encephalitides caused by the human immunodeficiency virus, lend further factual support to the hypothesis of a viral etiology, albeit unspecified, in both von Economo's and postencephalitic Parkinson's diseases. PMID- 1757789 TI - Mast cells in brains during experimental allergic encephalomyelitis in Lewis rats. AB - We studied the number of mast cells and their extent of degranulation in brains of Lewis rats with acute experimental allergic encephalomyelitis (EAE), activity induced with guinea pig spinal cord and Freund's complete adjuvant. Non-immunized controls and EAE rats were killed on days 10, 11, 12, and 16 post-immunization (p.i.). The percentage of degranulated mast cells was significantly increased in EAE brains. Signs of degranulation were observed as early as day 10 p.i. Clinical EAE signs appeared from day 10 p.i. A significant change in mast cell number was not observed. The percentage of degranulated cells was largest at day 16 p.i., at a time when the inflammation had reached the thalamus. This indicates that mast cell degranulation may occur as a result of the inflammation. Collectively, the data suggest that mast cells may play a role in the pathogenesis of EAE. PMID- 1757790 TI - Discrete lesions in the sensorimotor control system. A clinical-topographical study of lacunar infarcts. AB - In 50 patients with computed tomography-verified small, deep, lacunar, infarcts from a prospective stroke registry, we studied the lesion site in relationship with the clinical syndromes pure motor stroke, sensorimotor stroke and ataxic hemiparesis. Seventy per cent (95% confidence interval: 57-83%) of the lesions were located in the posterior limb of the internal capsule or adjacent paraventricular region, affecting the corticospinal tract in pure motor stroke, as well as the thalamocortical tract in sensorimotor stroke, and the cerebellar (dentato(rubro)thalamocortical and corticopontocerebellar) pathways in ataxic hemiparesis. This most frequently involved area is supplied by the anterior choroidal artery, indicating that this artery is the predominant deep, penetrating artery involved in small vessel disease causing lacunar stroke syndromes. PMID- 1757792 TI - Upbeat nystagmus: clinicopathological and pathophysiological considerations. AB - We describe an electro-oculographic study of upbeat nystagmus in 4 patients, with neuropathological correlation in one. All patients had lesions in the pontine tegmentum. The electro-oculographic data may be explained by imbalanced vertical vestibular or smooth pursuit eye movement control. The nystagmus stopped or reversed direction during convergence or in supine head positions. We propose that changes in the intensity or direction of upbeat nystagmus that are induced by convergence or changes in head position, are caused by vertical imbalance in the otolithic-ocular reflex, when superimposed on an imbalanced vestibulo-ocular reflex (VOR). Imbalance of the otolithic-ocular reflex and the vertical VOR are caused by damage in the pontomedullary tegmentum. PMID- 1757791 TI - Influence of age, gender, height and education on vibration sense. A study by tuning fork in 192 normal subjects. AB - We measured perception time of the vibratory stimulus from a 128 cps tuning fork in 96 male and 96 female normal subjects equally subdivided into 8 age decades. The following sites were examined: clavicula, olecranon, styloid apophysis of ulna and radius, anterosuperior spina of ilium, rotula (patella), internal and external malleolus. Reproducibility between different examiners and between tests by the same examiner on different days was good. There was a marked regional variation with longer perception times at the distal regions of upper limbs. A non linear age-related decrease in vibration sense was found in all regions. Males had longer perception times at clavicula, females at distal limbs; the latter finding might be explained by shorter stature in females. Perception times at distal limbs were longer in subjects with higher education levels. The study provides normative data for vibration sense in different regions and defines the effects on it of age, gender, height and education. PMID- 1757793 TI - The effect of pancreatic islet transplantation on experimental diabetic neuropathy. AB - Quantitative light and electronmicroscopical morphometric techniques were used to determine the effect of pancreatic islet transplantation on experimental diabetic neuropathy. Groups of STZ-diabetic rats were given islet transplants at 3 weeks after diabetes onset (prevention) and at 6 months after diabetes onset (reversal). Comparisons were made with onset controls, age-matched non-diabetic controls and untreated diabetic controls 6 months later (n = 8 for all groups). Euglycaemia and normal levels of glycosylated haemoglobin were achieved in both groups of diabetics after islet transplantation. Loss of body weight in diabetic animals was prevented by early islet transplantation, but was only partially reversed following delayed islet transplantation. Normal growth of myelinated fibres and axons during development was retarded in untreated diabetics, but was normal in rats given islet transplants soon after the onset of diabetes (cross sectional perimeter and area). Diabetics transplanted with islets after a delay had myelinated fibres and axons with diminished calibre. Teased fibre preparations of nerves from diabetics which had received islet transplants showed no excess of abnormalities. This study has shown that the development of certain structural abnormalities of peripheral nerve fibres is prevented in diabetic rats which receive transplants of islets of Langerhans soon after the onset of diabetes. However, once established abnormal fibre morphology can not be completely ameliorated merely by achieving and sustaining euglycaemia through delayed islet transplantation. PMID- 1757794 TI - Effects of 4-aminopyridine on protein phosphorylation in heat-blocked peripheral nerve. AB - The topical application of 4-aminopyridine (4-AP) reverses within 1-3 min the partial conduction block that results from heating 5-mm segments of rat posterior tibial, peroneal and sural nerves to 45 degrees C for several minutes. Nerves previously blocked in vitro or in vivo were incubated in vitro in the presence of [gamma-32P]ATP. The rate of phosphorylation of soluble nerve proteins that had entered the media was determined. Labeled proteins were separated electrophoretically and autoradiograms prepared. We found that 5 mM 4-AP increases the phosphorylation rate in heat-blocked nerve by approximately 50 fold. The process is calcium-dependent and is heat-labile. Soluble proteins with a molecular weight in the 53-55 kDa range are preferentially but not exclusively phosphorylated in the presence of 4-AP at levels effective in restoring conduction. The results suggest that the potassium channel blocker 4-AP may restore conduction by inducing changes in channel proteins. PMID- 1757795 TI - Increased growth of myoblasts from hypertrophic muscles in syringomyelia. AB - Proliferation and differentiation of myoblasts from hypertrophic muscles were studied "in vitro" in two cases of syringomyelia with muscle hypertrophy (MH). Their myoblast growth was compared with that of muscle cells sampled on the contralateral side in the same patients and in control subjects. The effect of a circulating factor was tested using patient sera in place of fetal calf and horse sera. The results showed that MH cells were morphologically abnormal (giant and granular). MH myoblasts proliferated more rapidly than contralateral and normal myoblasts, their fusion was accelerated and the resulting myotubes synthesized higher levels of protein. MH sera increased these effects. Serum factors are therefore likely to be involved in "in vivo" muscle hypertrophy. These findings suggest that the pathogenesis of muscle hypertrophy in syringomyelia involves acquired abnormalities due to molecules released in response to neural lesions. PMID- 1757797 TI - Distribution of calcium in central nervous system tissues and bones of rats maintained on calcium-deficient diets. AB - Current changing epidemiological pattern in the Western Pacific area suggests a contribution of the environmental factors to the pathogenetic process of amyotrophic lateral sclerosis (ALS). The condition of unbalanced mineral levels found in the soil and drinking water samples from the ALS foci showing low content of calcium (Ca) and magnesium (Mg) plus high content of aluminum (Al) was experimentally mimicked in this study using rats. In the groups fed low Ca, low Ca-Mg, and low Ca-Mg plus high Al diets, serum Ca levels were lower than that in the group fed the standard diet. Ca content of CNS tissues showed higher values in the unbalanced diet groups, especially in the spinal cord of low Ca-Mg plus high Al diet group, than those in the standard diet group, determined by inductively-coupled plasma emission spectrometry (ICP). Ca content in heart, liver, kidney, and abdominal aorta in groups fed low Ca-Mg, and low Ca-Mg plus high Al diets was higher than that in low Ca, and standard group. Ca content in muscle in the three unbalanced diet groups was significantly higher than in the standard diet group. Ca and Mg contents in lumbar spine and cortical bone showed lower values in the unbalanced diet groups than those values in the standard diet group. These findings suggest that under the condition of derangement of bone mineralization induced by unbalanced mineral diets fed to the experimental rats, Ca and Mg may be mobilized from bone, keeping their content in soft tissues, including CNS tissue, for utilization of vital activities, thereby resulting in a deposition of Ca while maintaining an almost normal value of magnesium in the CNS tissues. PMID- 1757796 TI - Fibronectin in plasma and CSF: evidence for its intrathecal synthesis. AB - A new methodology, using electroimmunodiffusion, has been described for the determination of fibronectin (Fn) in plasma and CSF. Fn was determined in the plasma of 35 normal subjects, and in the plasma and the CSF of 86 patients: 10 controls, 17 definite MS, 15 other inflammatory processes, 11 degenerative diseases, 13 peripheral neuropathies and 20 other neurological diseases. The normal mean was 354 +/- 53 micrograms/ml in plasma, not influenced by sex or age, and in the CSF 2.3 +/- 0.85 micrograms/ml. A significant increase of plasma Fn was observed in each of the patients-group. In the CSF an increase of Fn was observed predominantly in inflammatory processes but not in MS. An intrathecal synthesis of Fn was established in 24/76 patients, most often in inflammatory (9/15) processes but rarely (3/17) in MS. The intrathecal synthesis was suspected from the CSF Fn/CSF Albumin ratio and calculated using a formula derived from the principles previously described for IgG intrathecal synthesis. It represents the principal source of Fn increase in the CSF. In all inflammatory processes (including MS) the eventual influence of corticoids, immunosuppressive or anti inflammatory drugs has not been established. The significance of the CSF Fn level in MS is discussed with regard to the recent demonstration of its presence within MS lesions and on macrophages in plaques. PMID- 1757798 TI - Enhanced proteolytic activities in cultured fibroblasts of Alzheimer patients are revealed by peculiar transketolase alterations. AB - Characteristic alterations of transketolase (TK) in extracts from cultured Alzheimer fibroblasts have previously been reported (Paoletti et al. (1990) Biochem. Biophys. Res. Commun., 172: 396-401). These abnormalities, encountered in 9 out of 13 Alzheimer patients, were revealed following isoelectric focusing and consisted of enzyme forms having unusually high alkaline pI values (alkaline bands). The present work has shown that immunologically detected alkaline bands were progressively expressed when Alzheimer fibroblasts were incubated for three weeks without medium changes. Full expression of the altered enzyme pattern was not linked to relative cell density in the petri dish; rather, it appeared to be dependent directly on the time elapsed since cell confluence was reached. Alkaline bands could artificially be induced also in both crude and pure TK preparations from normal cells by a treatment with commercial proteases, particularly chymotrypsin. Moreover, specific inhibitors of endogenous cysteine proteases were capable of abolishing TK alkaline bands in Alzheimer fibroblasts thus turning a pathological into a normal enzyme pattern. Results obtained suggest that Alzheimer fibroblasts contain enhanced Ca(2+)-independent cysteine proteolytic activities as compared to normal and other pathological cells. These enzymes, exhibiting chymotrypsin-like activity, might exert their degradative effects at the time of cell extraction using TK and probably other cell components as potential substrates. However, peculiar TK abnormalities represent so far an useful biochemical marker detectable in fibroblasts of living Alzheimer patients and closely associated to this neurological disorder. PMID- 1757799 TI - Arabinitol enantiomers in cerebrospinal fluid. AB - D-Arabinitol is a metabolite of Candida species, and its presence in serum above endogenous concentration may indicate disseminated candidiasis. The o trifluoroacetylated derivatives of arabinitol enantiomers in cerebrospinal fluid (CSF) were separated using perpentylated cyclodextrin capillary columns and measured by selected ion monitoring using negative chemical ionization mass spectrometry. The presence of D-arabinitol was confirmed using highly specific D arabinitol dehydrogenase. The mean D/L-arabinitol ratio, 16.7 +/- 4.8 (range: 8.6 22.8), in CSF of the "controls" is approximately 10-fold higher than the ratio previously found in normal serum and urine. At the same time, the mean L arabinitol concentration, 0.13 +/- 0.05 (range: 0.09-0.2), is virtually identical to that in serum. Therefore, the high D/L-arabinitol ratio in CSF is attributed to D-arabinitol. Persistently high D/L ratios were found in a variety of diseases (without Candida infection). The finding of D-arabinitol in CSF suggests that serum D-arabinitol may originate from the brain or the spinal cord, rather than from resident Candida species in the gut, and that the accumulation of D arabinitol in CSF may be caused by non-consumption or, conversely, the high concentration may be maintained in order to have it readily available for metabolism in the brain. PMID- 1757800 TI - The molecular genetics of familial Creutzfeldt-Jakob disease in France. AB - Five French families with Creutzfeldt-Jakob disease (CJD) were found to have either of 2 different point mutations (at codons 178 and 200) in the amyloid precursor gene (PRNP) on chromosome 20. The ancestry of these and other CJD families outside of France suggests that the codon 178 mutation had a northern European origin, while the codon 200 mutation originated in central Europe and the Mediterranean basin. Evidence is presented that the mutations either cause or predispose to familial forms of CJD, and also influence their phenotypic expression, although considerable clinical and neuropathological heterogeneity may occur between and even within families having the same mutation. Experimental transmission of disease was successful in 4 of 5 inoculated cases, comparable to the transmission rate in sporadic CJD. PMID- 1757801 TI - A case of intracranial chordoma associated with pituitary adenoma. AB - We report a patient who had pituitary adenoma and parasellar chordoma coincidentally, with neither irradiation nor a history of head injury. Preoperative computed tomographic (CT) scan had shown an intrasellar mass that infiltrated into the right cavernous sinus. Histopathologically the intrasellar mass was diagnosed as pituitary adenoma and the other mass as chordoma. We present clinical, radiological and histopathological findings, and discuss previously reported cases with multiple intracranial tumours. PMID- 1757802 TI - Contralateral extradural hematoma following craniotomy for traumatic intracranial lesion. Case report. AB - The authors report the case of a patient in whom a contralateral extradural hematoma developed immediately after craniotomy for a traumatic intracranial lesion. Contrary to other reported cases but one, intraoperative brain bulging was not observed in this case. The pathophysiology of this complication is discussed. Immediate postoperative CT scan in patients who do not improve as expected is recommended for the early detection of this complication. PMID- 1757803 TI - A cervico-dorsal intramedullary epidermoid cyst. Case report and review of the literature. AB - Intramedullary epidermoid cysts are rarely observed. Only a little more than 30 cases have been reported in the literature. The authors have treated a 51 year old woman with a cervico-dorsal intramedullary epidermoid tumor associated with a syringomyelia. The frequency of this lesion, its CT and MRI appearance and the possibility of a preoperative diagnosis are discussed. PMID- 1757804 TI - Aspergillosis of spine. A case report. AB - Aspergillosis of spine is a very rare entity generally seen secondary to a primary focus in the lung with or without immune suppression. The authors report one case of aspergillosis of spine without evidence of a primary elsewhere or a predisposing cause. PMID- 1757805 TI - Posttraumatic diffuse cerebral lesions. Relationship between clinical course, CT findings and ICP. AB - One hundred and fifty patients with posttraumatic diffuse cerebral lesions were reviewed. Criteria of inclusion were immediate coma and CT appearance of diffuse lesions, that were classified as follows: (a) Diffuse axonal injury (70 cases): patients with normal CT scan (50 cases) and patients with shearing injury (focal hemorrhages in corpus callosum, basal ganglia and brain stem; gliding contusions) (20 cases); (b) Diffuse brain swelling (80 cases): reduced or absent lateral ventricles, absence of 3rd ventricle and basal cisterns. Many of these patients had either subarachnoid haemorrhage or subdural blood effusion. Clinical course and mortality rate were in a ranking order in the considered groups. Patients with normal CT had a less severe coma and a better outcome than patients with shearing injury and diffuse brain swelling. There was evidence of high intracranial pressure in 75% of the patients with brain swelling, whereas no patient with normal CT had ICP elevation. Diffuse axonal injury represents a primary posttraumatic diffuse lesion. Secondary vascular involvement, due to hypoxia, shock and other unknown causes, is responsible for the appearance of vasoparesis, hyperemia and diffuse brain swelling. PMID- 1757806 TI - Validation of a prognostic system in severe brain-injured patients. AB - Seventy-six patients with severe isolated head trauma (GCS score of 7 or less) were prospectively studied in order to valuate the prognostic power of the APACHE II system. In nonsurvivor patients the APACHE II score was higher than in survivor patients (24.7 +/- 3.2 (SD) vs 18.7 +/- 3.1; p less than .001). With an APACHE II cut-off point of 20 the sensitivity was 100% and the specificity was 70% while a cut-off point of 21 the sensibility decreased to 97.2% but the specificity increased to 72.5%. We conclude that the APACHE II is an effective mean to predict the prognosis of severe brain-injured patients. PMID- 1757807 TI - Nonsuture closure of arterial defect by vein graft using isobutyl-2-cyanoacrylate as a tissue adhesive. AB - Nonsuture repair of intracranial blood vessel is still a challenging issue in neurosurgery. In this experimental study isobutyl-2-cyanoacrylate was used for nonsuture repairing of carotid artery to observe its histotoxicity. Isobutyl-2 cyanoacrylate was dropped over the edge of defect on carotid artery of rat under the surgical microscope and jugular vein was placed to cover the defect. Rats were divided in 6 group according to postoperative survival period (2, 5, 7, 14, 21, 28 days respectively). The carotid arteries were patent of all rats according to angiography and autopsy specimen. Histopathological results showed that: the changes are mainly inflammatory respons +, there was no necrotic tissue at any time the healing progress and no significant differences in the vein graft. Therefore isobutyl-2-cyanoacrylate is considered helpful and safe adhesive material for the nonsuture repair of blood vessel. PMID- 1757808 TI - Laser therapy for the treatment of brain tumors. AB - The author examine the specific cases where laser therapy may be indicated for the treatment of brain tumors. The different types of lasers currently available are described and the effects on the tissue, at different powers and with different modalities of use, are reported. On the basis of experience reported in literature, the Author describes the characteristics and the fields of application of the 1.32 nm Nd:YAG laser, the superpulse CO2 and the Nd:YAG with sapphire tips for contact laser surgery. The advantages of laser surgery as opposed to the traditional techniques in the most frequently observed tumors, are also described. PMID- 1757809 TI - Postoperative CSF problems after spinal and lumbar surgery. General review. AB - Although the dura is frequently traumatized in surgery, and during lumbar punctures, it is surprising that the "CSF problem" is a rare complication in the surgical treatment for herniated intervertebral disc (0.1%); and exceptionally rare at cervical or dorsal level. In the upright position the CSF pressure at the site of the potential leak is greater in the lumbar region, lumbar operations are more frequently performed than cervical, and, perhaps, also because cervical operations are performed by fewer surgeons with greater specific experience. The purpose of this work is to describe the etiopathology, the symptomatology, the diagnosis and treatment of early and delayed CSF problems. PMID- 1757810 TI - Acute spontaneous subdural haematoma. Description of four clinical cases. AB - Four cases of acute spontaneous subdural haematoma are described. A review of the literature reveals the rarity of this pathology. The several etiological possibilities are discussed. The clinical onset may simulate other cerebrovascular diseases. The prognosis is correlate to the neurological findings at the operations. PMID- 1757811 TI - A window of opportunity. PMID- 1757812 TI - Phases of second stage labor. Four descriptive case studies. AB - In recent years, the second stage of labor has become an area of interest to a number of observers who have described divisions or phases with behavioral characteristics. Using a descriptive case study design, four normal nulliparous women in spontaneous second stage labor were videotaped from the occurrence of involuntary bearing-down efforts or the recognition of complete cervical dilation until birth. Analysis of these videotapes, the accompanying narrative transcripts, and uterine monitor tracings provided evidence that some behaviors changed over the progression of the second stage. These changes could be divided into three behavioral phases that the nurse/midwife can identify in order to recognize the typical pattern of progression and possible deviations from normal. PMID- 1757813 TI - Certified nurse-midwifery care of the postpartum client. A descriptive study. AB - This article presents the findings of a small, descriptive, exploratory study aimed at identifying the content and process components of certified nurse midwifery care in the postpartum period. The conceptual framework, methods, and analysis were derived from the research of E.J. Lehrman, who identified components of CNM antepartum care. Lehrman's components of prenatal care were all found to be present in the postpartum period, but new data emerged. These data generated three distinctively new categories, ie, therapeutic techniques, lateral relationship, and empowerment. Albeit from a small study, our findings support previous research suggesting aspects of CNM care that might be partially responsible for improved perinatal outcome documented in various populations where CNM care has been established. The article concludes with a discussion of these implications for practice and the need for further definition of the profession of nurse-midwifery. PMID- 1757814 TI - Bacterial vaginosis and its implication in preterm labor and premature rupture of membranes. A review of the literature. AB - Preterm delivery continues to occur in 5% to 10% of all births, with a perinatal mortality rate between 50% and 80%. In recent years, the role of infection with lower genital tract organisms in precipitating preterm labor/delivery and premature rupture of membranes has come under considerable study. This article reviews the mechanisms by which infection may play a role in these problems, with a specific focus on bacterial vaginosis. Clinical management issues are addressed, including screening of prenatal patients, diagnostic criteria, and treatment possibilities. PMID- 1757815 TI - Laryngeal papillomas in infants and children. Relationship to maternal venereal warts. AB - A variety of studies has been directed at establishing the association between human papillomavirus (HPV), as manifested in the adult as a sexually transmitted disease, and laryngeal papillomas found in infants and children. In spite of substantial evidence for the transmission of HPV from women to their infants during childbirth, this association remains unknown to most clinicians in the specialty areas of childbearing and pediatrics. Nurse-midwives find evidence of venereal warts in 1% to 35% (1) of their pregnant clients, depending upon the subpopulation under consideration. A potential sequela of this common gynecologic finding is the growth of papillomas in the larynx of infants who are born to these women. Such growths are not immediately apparent and may be quite difficult to diagnose when they usually become symptomatic, between the ages of two and five years. Clinical symptoms are similar to pediatric findings in croup, asthma, and common upper airway infections. Education of both clinicians and patients regarding potential risks to progeny of infected adults will serve to guide diagnostic attempts in the pediatric population. PMID- 1757816 TI - Fatigue in early pregnancy. An exploratory study. AB - The experience of fatigue in early pregnancy was studied, using a general model of fatigue as the conceptual framework. A convenience sample of 30 women, age 20 35 years, who were at less than 20 weeks' gestation and without health problems were included in the study. Physiologic, psychological, and environmental factors were measured and related to the occurrence and intensity of fatigue. Pearson correlations and content analysis were used to analyze the data. Results showed that a large portion of the sample (90%) experienced fatigue and that this fatigue had a significant impact on their ability to maintain personal and social activities. Significant correlations were observed between fatigue and the physiologic variables of nausea and feeling tired upon awakening from sleep. There was no significant relationship between fatigue and environmental variables such as number of hours worked or the number of children living in the home. In addition, significant correlations were observed between fatigue and psychological variables that included depression, anger, anxiety, and confusion. These data suggest that fatigue is a significant problem for pregnant women and is not relieved by rest. These data further suggest that the fatigue may be related to other physiologic changes, perhaps hormonal, that mediate physiologic and psychological variables, including fatigue. PMID- 1757817 TI - The importance of non-master's degree options in nurse-midwifery education. PMID- 1757818 TI - Hospital setting for birth and use of medical procedures in low-risk women. AB - This study examined the use of selected medical procedures in low-risk women during childbirth. Data from the 1980 National Natality Survey merged with an American Hospital Association annual survey for the same year were used to assess the frequency with which low-risk women in the United States received certain childbirth procedures and to determine whether their use varied by the hospital setting for birth. Stratified analysis was used to assess the relation of hospital level for delivery with the use of electronic fetal monitoring, labor induction, and primary cesarean delivery in low-risk women, with control for potential confounding factors. As the level of available perinatal technology increased, the use of these procedures increased. Results of the study suggest that low-risk women may have received excess interventions and confirm the need for further examination of care procedures for this group. PMID- 1757819 TI - Early maternal attachment behaviors of adolescent and adult mothers. AB - This comparison of observed attachment behaviors of 184 medically indigent, low risk, inner-city adolescent and adult mothers addresses three critical questions unanswered by current research regarding the maternal attachments behaviors of adolescents. The 69 mothers aged 14 to 17 and the 36 mothers aged 18 to 19 exhibited significantly fewer maternal attachment behaviors during in-hospital infant feedings than a control group of 79 mothers aged 20 to 24. Verbal reports of adolescent and adult mothers were not reliable indicators of actual attachment behaviors. Two-way analyses of variance, statistically controlling for other background factors and amount of infant contact, did not diminish the impact of maternal age. However, rooming-in and educational levels appropriate for age both had additional independent impacts on maternal attachment scores. PMID- 1757820 TI - Prevention of infant mortality. An agenda for nurse-midwifery. AB - A major health objective of the United States government and the World Health Organization is the reduction of infant mortality by the year 2000. Significant progress in the reduction of infant mortality has been made internationally simply as a consequence of general improvements in public health and nationally as a consequence of increased technological sophistication. Recently, however, there has been an attenuation in the rate of decline, and it becomes necessary to address the unsolved issues that continue to affect morbidity and mortality in the first year of life. Year 2000 objectives related to infant mortality include the reduction of low birth weight and increasing access to prenatal care. Socioeconomic, behavioral, medical, and obstetric factors associated with low birth weight and lack of prenatal care are cited. Personal and political agenda targeted to the achievement of the public health goals are proposed. PMID- 1757821 TI - Postpartum patients' knowledge, risk perceptions, and behaviors pertaining to childhood injuries. AB - The purpose of this study was to assess postpartum patients' knowledge, risk perceptions, and behaviors pertaining to a variety of childhood injuries. Although the respondents did demonstrate some knowledge of injury prevention strategies, deficits were noted in the areas of burns, motor vehicle injuries, drownings, and falls, as well as in the concept that injuries, in some children, are unavoidable. Results showed that greater than 50% of mothers did not know the temperature of their hot water tank, 22.4% who had other children under the age of four did not use car safety seats with them, and only 43% of the mothers knew how to perform infant cardiopulmonary resuscitation. Recommendations for program development in parenting classes are included in addition to the roles of nurses and nurse-midwives in injury prevention program activities. PMID- 1757822 TI - Maternal-fetal conflicts. Ethical and legal implications for nurse-midwives. AB - The problem of maternal-fetal conflict presents both ethical and legal challenges to birth attendants as well as to policymakers. This essay suggests that a crisis intervention approach to such conflicts fosters an adversarial view of the relationship between the pregnant woman and her fetus, which can be divisive and counterproductive. A better approach to maternal-fetal conflicts emphasizes mutually held goals rather than countervailing rights and uses the doctrine of informed consent to enhance the pregnant woman's ability to make responsible choices for both herself and her fetus. Nonphysician birth attendants can take a leading role by employing client-centered professional values to develop and extend this cooperative approach to maternal-fetal conflicts. PMID- 1757823 TI - Midwives' role in safe motherhood. PMID- 1757824 TI - An overview of nurse-midwifery education and accreditation. PMID- 1757825 TI - Management of the nuchal cord in relation to vaginal delivery. PMID- 1757826 TI - One out of every nine women ... PMID- 1757827 TI - Rationale for the revision of oxytocin administration protocols. AB - A physiologic rationale, based on a review of the literature, is provided for implementing a protocol for labor induction or augmentation with intravenous oxytocin infusion. Oxytocin dosage should simulate the amount normally released endogenously during labor. Recent studies suggest that smaller dose regimens are as effective as previous larger dose regimens and that adverse effects of oxytocin are dose related. Nurses must know the relationship between the physiology of normal labor and the pharmacokinetics and safe administration of oxytocin during labor. PMID- 1757828 TI - HIV-seropositive childbearing women. Nursing management. AB - With the implementation of the recommendation of the American College of Obstetricians and Gynecologists to screen all women who are at increased risk for HIV infection, more asymptomatic infected women will be identified. Obstetric and neonatal nurses who learn more about maternal and infant HIV infection can determine effective nursing interventions. Early planning is necessary to ensure that individualized, comprehensive care is available upon discharge. PMID- 1757829 TI - Creating a unit-specific charging system. AB - A totally nurse-dependent charging system developed specifically for the labor and delivery suite at the University of Maryland Medical System is described in the article. This easy and effective method of charging was incorporated into an already existing patient census and classification system. The number of relative value units has increased by more than 30%, and the amount of revenue billed has increased by more than $800,000 in the first 10 months after implementation. PMID- 1757830 TI - Maternal confidence in coping with labor. A self-efficacy concept. AB - The clinical study of labor pain suggests that a woman's confidence in her ability to cope with labor contributes significantly to her perception of pain during labor. Self-efficacy theory is examined as a framework for evaluating women's confidence in their ability to cope with labor. The major propositions of self-efficacy theory are described and related to the experience of women approaching labor. The implications for nursing practice are presented, and directions for the study of maternal confidence are proposed. PMID- 1757831 TI - Infant responses to saline instillations and endotracheal suctioning. AB - The study examined the effects of endotracheal suction with and without saline instillation on neonates with respiratory distress. In a completely counterbalanced factorial-within-subjects design, 27 intubated neonates were randomly assigned to two orders of presentation of treatment conditions. Heart rate and blood pressure were continuously recorded throughout both treatment conditions. The ratio of arterial oxygen tension to alveolar oxygen tension was used to assess oxygenation. Results indicated that clinically stable newborns tolerated instillations of 0.25-0.5 ml. The suctioning protocol used in this study minimized changes in infants' heart rates and blood pressures. PMID- 1757832 TI - Breastfeeding and employment. AB - Breastfeeding problems, outcomes, and satisfaction of married, well-educated first-time mothers who returned to work within six months postpartum were compared to those of mothers with the same characteristics who stayed at home. Mothers who planned to work after giving birth anticipated and experienced shorter durations of breastfeeding than did those who planned to remain at home. Breastfeeding experiences and satisfaction among working mothers differed little from the experiences and satisfaction of their nonworking counterparts; however, employment prior to two months postpartum exerted some negative effects on breastfeeding outcomes. PMID- 1757833 TI - The role of nursing in preventing violence against women. AB - Violence against women is a significant problem at every age. While nurses have increased their role in identifying and managing cases of women who have experienced physical and sexual abuse, they have been less active in preventing violence. Effective prevention requires an understanding of the prevalence and seriousness of the problem, awareness of the societal forces that foster and sustain it, and application of feminist principles to counteract those forces. The incidence of rape and battery in contemporary society is highlighted, and the societal forces of devaluation of women, power inequity, and treatment of women as property that maintain this destructive behavior are outlined. Preventive nursing actions derived from feminist philosophy that are applicable in clinical practice are discussed. PMID- 1757834 TI - The gastrointestinal management of patients undergoing heart transplantation. AB - Between March 1985 and December 1989, 86 patients underwent heart (80) or heart lung (6) transplantation. Thirty-seven (43%) developed one or more significant gastrointestinal problems. Dyspepsia and gallbladder disease were common, but easily managed. Cytomegalovirus disease occurred in 25 patients (29%) and required aggressive investigation and early therapy with ganciclovir; all patients so treated responded satisfactorily. Features of acute peritonitis were seen in 6 patients and required exploratory laparotomy in 4. Non-Hodgkin's lymphoma of the stomach in one patient has regressed following a combination of reduction in immunosuppressive therapy and a course of chemotherapy. The development of hepatitis or severe liver dysfunction of unknown cause has been associated with significant morbidity and mortality. Since this study was undertaken, the incidence of gastrointestinal complications has been greatly reduced by modifications to our immunosuppressive and anti-infection prophylactic drug protocols. Nevertheless, such complications still occur and it is important that the gastroenterologist should understand the need for urgent and intensive investigation and therapy. PMID- 1757835 TI - Comparison of antimicrobial susceptibilities among hospitalized and nursing home patients from Oklahoma. AB - Antimicrobial susceptibility results were compared for 13,090 isolates recovered from patients of Oklahoma hospitals and nursing homes. The most striking results confirm earlier suspicions that nursing home patients represent the largest pool of methicillin-resistant (greater than 60%) Staphylococcus aureus. PMID- 1757836 TI - HIV seroprevalence in Oklahoma childbearing women. AB - From October 1989 through September 1990, we conducted an unlinked seroprevalence survey in Oklahoma to determine the prevalence of human immunodeficiency virus, type 1 (HIV) in women at the time of childbirth. Blood specimens obtained from 41,809 newborns in conjunction with the state's newborn metabolic screening program were tested for HIV after personal identifiers were removed. The overall HIV seroprevalence rate was 0.02% (10/41,809). Rates were highest for mothers aged 30 to 39 years (0.06%, 3/5,158). No difference was found between the HIV seroprevalence rates for women residing in standard metropolitan areas (MSAs) of the state (0.03%, 6/21,105) and women residing in non-metropolitan areas (0.03%, 3/11,904). When compared to other states where surveys have been done, Oklahoma's rate of HIV infection in childbearing women was low. PMID- 1757837 TI - Endometrioid carcinoma arising in endometriosis after 21 years: a case report. AB - Endometriosis is an odd disease that is at times devastating in the destruction of surrounding tissue. Yet, in contradiction, other cases are widespread, longstanding, benign, and totally asymptomatic. It has been reported throughout the body. PMID- 1757838 TI - On a wrong right. PMID- 1757839 TI - Principles of oncology: how radiation therapy works. AB - Radiation therapy remains the primary mode of treatment for many types and stages of cancer as well as playing an extremely important adjunct role in the treatment of many other malignancies, often in combination with medical and surgical oncology. The combination treatments often yield cure and long-term control rates far in excess of single modality treatment. PMID- 1757840 TI - The failed appointment. AB - OBJECTIVE: To determine reasons for failed internal medicine clinic appointments. DESIGN: A retrospective telephone survey of patients within one month of a failed appointment. SETTING: An ambulatory teaching clinic for indigent patients staffed by 30 internal medicine residents where patients have scheduled visits every 30 minutes. PATIENTS/PARTICIPANTS: From the 1,622 scheduled patient visits, the names of 405 patients who failed their appointments were selected for further contact. Successful contact was established with 100 patients. MEASUREMENTS AND MAIN RESULTS: The patients completed a telephone survey administered by residents and students regarding demographics, general health, reasons for failed appointment, and satisfaction with the clinic. Transportation problems accounted for 13% of missed visits, forgetfulness accounted for 11%, personal or family illness and rescheduling problems accounted for 8% each. Miscellaneous reasons accounted for the remainder. Seventeen percent of patients who missed their appointments feared the encounter, but none volunteered this as a reason for their no-show. Fifty-one percent of patients felt that the failed appointments could not have been prevented. Ninety percent of those surveyed were satisfied with their clinic physician, and 82% were seen on-time when appointments were kept. CONCLUSIONS: Lack of transportation appeared to be the most prohibitive factor in continuity of care among this indigent population. Patients are generally seen on-time and are satisfied with their care. Financial pressure does not appear to keep people away. Fear of the physician encounter and forgetfulness may be areas for improved patient education. PMID- 1757841 TI - [A case report of lymphoepithelial cyst in the parotid gland]. AB - A 57 year-old Japanese male was seen with the chief complaints of left parotid gland swelling, pain, trismus. At the initial visit, a subcutaneous mass, measuring 50 x 70mm, was seen in the left parotid region. The mass was moderately tender and the consistency was soft anteriorly and elastic firm posteriorly. The mobility was restricted with no change in the skin covering the mass. The saliva from the left parotid gland was normal in colour and contents. Various imaging modalities were done preoperatively including CT, MRI, ultrasonography and aspiration biopsy under the ultrasonographic guide. None was thus conclusive for the differential diagnosis and our tentative diagnosis was a cystic lesion in the parotid gland. A partial parotidectomy was performed under general anesthesia and the cystic lesion, measuring 20mm in diameter, was found in the deep lobe. The cyst showed no connection to the external ear canal, and tracts and fistulae were absent. Histopathological report lead to the definite diagnosis of lymphoepithelial cyst. A mild and incomplete facial palsy on the left had been noted for more than 10 years and this, however, improved after the surgery. PMID- 1757842 TI - [Application of fuzzy theory for optokinetic pattern test]. AB - The optokinetic pattern test for optokinetic nystagmus is performed to diagnose equilibrium disorders on clinical examination. We constructed computer assisted instruction (CAI) algorithm based on knowledge of expert for optokinetic pattern (OKP) diagnosis theoretically based Fuzzy reasoning derived from Fuzzy theory to ascertain the possible application of CAI to OKP and to develop a useful diagnostic tool. The algorithm was constructed by rules of fuzzy reasoning using analysed data of diagnostic modes of one expert, consisting of six variables, and of 30 normal and 22 abnormal patterns of optokinetic nystagmus which were diagnosed by the expert. The results derived from the fuzzy reasoning and those obtained by expert agreed with 96% in this test battery. In addition, a consistency of 87.3% was obtained after comparison with another 251 OKP patterns which diagnosed by the same expert and estimated by this algorithm. This algorithm incorporating fuzzy theory is concluded to be useful in obtaining results of the same as those of an expert for diagnosing the equilibrium disorders. Furthermore, CAI using Fuzzy theory is confirmed to have good potential as a diagnostic tools. PMID- 1757843 TI - [Effects of frequent antral lavage on chronic sinusitis in children]. AB - Eighty cases of pediatric sinusitis (4 to 15 years old, averaged 8 years old) were treated with frequent antral irrigations. Antral puncture was made through the inferior meatus with a Kyoto University needle under topical or general anesthesia. Then a plastic tube of 14G Medicut intravenous cannula was left in place to serve as an indwelling catheter. Antral lavages were performed through this tube 3 times daily for 7 to 10 days. The opacity of the maxillary sinus at post-treatment was improved significantly compared with that at pre-treatment in Waters view. This improvement was continued even at about 5.7 months after treatment. The opacity of the ethmoid sinus was also improved significantly after the treatment in occipito-frontal view. Our results suggest that the frequent antral lavage is an useful therapeutic modality for pediatric sinusitis. PMID- 1757844 TI - [A comparative study between the clinical and autoptic findings in cases with malignant tumor in the head and neck]. AB - In 106 autopsies of patients in Kitasato University Hospital from 1974 to 1989, who had died of malignant tumor in the head and neck, the relationship between the clinical diagnosis and its autoptic finding was retrospectively investigated. The result was summarized as follows. 1. Characteristics in 98 cases other than malignant lymphoma: 1) Local recurrence was detected by autopsy in 60 cases (61%) among 98. Discrepancy between clinical diagnosis and autoptic findings was recognized in 10 cases (10%), in whom 4 false positive cases by clinical diagnosis were included and it was considered that the rate was relatively high. 2) The metastatic lymph nodes were demonstrated by autopsy in 50 cases (51%). Discrepancy between clinical diagnosis and autoptic findings was found in 37 (38%), 35 of them were clinically diagnosed to be negative. However, in 35 of them it was considered that the discrepancy had not influenced their fatal courses. 3) Metastases to distant organs were demonstrated by autopsy in 49 (50%). Discrepancy between clinical diagnosis and autoptic findings was found in 39 (40%). 33 of them were clinically diagnosed to be negative. The discrepancy concerned with the causes of death was shown in 5 cases. 2. Characteristics in 8 cases of malignant lymphoma: Discrepancy between clinical diagnosis and autoptic findings of distant metastases was frequently observed but the discrepancy concerned with the causes of death was not shown. There were 2 cases in which side effect of chemotherapy may cause poor prognosis. PMID- 1757845 TI - [Effects of intravenous injection of salicylate on the spontaneous discharge rate of the cochlear nerve]. AB - This study was aimed to elucidate the effects of salicylate on the cochlear nerve by recording the spontaneous activity in guinea pigs. After guinea pigs were given salicylate (200 mg/kg) intravenously, the transient reduction in cochlear spontaneous activity and the elevation over the subsequent 10-20 minutes were observed in three of four fibers recorded for more than 30 minutes. The mean spontaneous discharge rate of 102 fibers after administration of salicylate (200 mg/kg) was not significantly higher than the control values from 30 to 120 minutes after salicylate administration, while that rate of 112 fibers after administration of salicylate (400 mg/kg) was significantly higher. The observed changes in spontaneous activity due to salicylate administration may represent the evidence of a tinnituslike phenomenon in guinea pigs. PMID- 1757846 TI - [Neuro-otological study on Behcet disease]. AB - It seems acceptable that pathological brain stem lesions exist in the patient with Neuro-Behcet disease (NB). However, only few reports have been published in this field. We report the neuro-otological findings in 33 patients who fulfilled the diagnostic criteria of Behcet disease completely or incompletely. The patients were classified into 2 groups: one is group of NB and the other is a group of Behcet disease without NB (non-NB). Furthermore, the latter was divided into 2 subgroups of patients with dysequilibrium and patients with normal equilibrium. They underwent equilibrium function tests, such as body balance test, gaze test, spontaneous and positional nystagmus test, eye tracking test (ETT) and optokinetic pattern test (OKP) by using electro-nystagmography (ENG). The following results were obtained. 1. Cerebellar and brain stem lesions were confirmed in all cases of NB group. 2. Most cases (6 of 8 cases) in the subgroup of dysequilibrium of the non-NB group showed peripheral vestibular disturbance. The other two patients were diagnosed to be vertebro-basilar insufficiency (VBI) and vascular Behcet disease with CNS disorder, respectively. 3. Nine of 13 patients in the normal equilibrium subgroup of the non-NB group were diagnosed to be neuro-otologically normal. However, we found two patients with peripheral vestibular disturbance and CNS disorder associated with hearing disturbance of the retrocochlear origin, respectively. 4. The neuro-otological examination is assumed to be useful to diagnose neuro-Behcet disease, to reveal the lesion site and the state of dysequilibrium in patients with Behcet disease. PMID- 1757847 TI - [Articulatory evaluation after mesopharyngeal reconstruction with the radial forearm flap]. AB - Soft palate and tonsil (mesopharynx) play an important role on articulation and swallowing. We must take care not to restrict these physiological function when we reconstruct the mesopharyngeal defect after cancer ablation. In order not to restrict the postoperative function of mesopharynx, we take it the more important to preserve the function of the residual tissue rather than to rebuild the lost function. We took notice of pliable nature of the radial forearm flap and tried to reconstruct mesopharyngeal defect in five cases with this flap. We analyzed articulatory function and velopharyngeal closure in these cases, postoperatively. Articulatory function was assessed on the results of intelligibility test with 100 Japanese monosyllables. In four cases out of five, about 70% of syllables were accurately heard. According to the Hirose's standard of speech function after the operation of oral and/or oropharyngeal cancer, those four cases were evaluated also to be excellent. Whether the resection was done beyond the uvula or not, proved not to have anything to do with the postoperative speech intelligibility. Although speech intelligibility once went down immediately after the operation, it improved around six months later. The improvement might be due to the following facts; The forearm flap was cicatrized postoperatively, disturbing the mobility. After the softening of the cicatrix began, the flap gradually recovered flexibility, which enabled surrounding structure to move more smoothly. Articulatory dysfunction was characterized as plosives tend to be misunderstood as nasals or affricates. Concerning nasality, the velopharyngeal closure was examined by fiberscope. Perfect closure was seen in two cases, near perfect in two cases, and insufficient in one case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757848 TI - [Detection of RS viral sequences in otitis media effusion from children]. AB - The role of respiratory syncytial virus (RS virus) in otitis media with effusion was studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (Nested PCR) were used to provide accurate methods for detection of RS viral sequences in the otitis media effusion from children. We could find RS viral sequences in 10/12 samples tested which had been collected during and even after natural outbreak of RSV in the community. These observations suggest RS virus as an important factor in the pathogenesis of otitis media with effusion. The disturbance of the local humoral and cell mediated immune response in the middle ear accompanied with RS virus infection may lead to the development of infection-induced inflammation and ventilatory compromise, development of suppurative and effusion, multiplication of low virulence pathogens and subsequent development of mucosal damage. PMID- 1757849 TI - [Clinical studies on attic retraction]. AB - Attic retraction was studied in 327 ears of 264 patients in whom photographs of the tympanic membrane were taken from 1983 to 1989. Attic retraction was investigated clinically on the basis of findings of the tympanic membrane in reference to the photographs and ear X-ray findings, including CT. Attic retraction was also observed in 4.5% of cases without inflammation, but its severity was mild. The incidence of attic retraction in cases of adhesive otitis media was 42.7% in mild adhesive otitis media (adhesive grade I) and 60.8% in severe adhesive otitis media (adhesive grade II), both incidences were significantly higher than the incidence of 23.8% in cases of otitis media with effusion. Thus, the incidence of attic retraction increased as the grade of adhesion became severer. In cases of otitis media with effusion, the incidence was significantly higher in the adult group (32.3%) than in the child group (17.4%). In many of the ears with otitis media with effusion, adhesive grade I and chronic otitis media, the severity of attic retraction was mild. There were more cases of milder retraction in the child group than in the adult group. Attic retraction underwent change with time in 2.8% of cases, and cholesteatoma occurred in 1.8% of cases. No improvement in attic retraction was achieved by insertion of a ventilation tube. Bilateral attic retraction was observed in 56.9% of the child group and 30.2% of the adult group, and the difference was statistically significant. Ear X-ray findings by Schuller's method revealed many ears with poorly developed mastoid cells and poor pneumatization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757850 TI - [Effect of inner ear immune response on vestibular function in guinea pigs]. AB - We examined vestibular dysfunction and histological damage caused by direct antigen challenge to the endolymphatic sac in guinea pigs. We observed spontaneous nystagmus every eight hours and performed caloric testing every week following endolymphatic sac secondary KLH challenge. Spontaneous nystagmus was seen in 12 of 18 animals, and nystagmus in all directed toward the unchallenged ear (paralytic). The caloric response time courses were classified into two types, which were irreversible type and reversible type after endolymphatic sac KLH challenge. The immune injury of animals with irreversible type was thought to be stronger than that of these with reversible type. The spontaneous nystagmus of irreversible type animals was longer than that of reversible type animals. The temporary vestibular dysfunction was thought to be similar to that observed in Meniere's disease. PMID- 1757851 TI - The eye of the beholder. PMID- 1757852 TI - The fluorescein disappearance test (FDT): an evaluation of its use in infants. AB - We report a prospective evaluation of the fluorescein disappearance test (FDT) in the diagnosis of lacrimal outflow obstruction in infants under 1 year of age. In a preliminary study of 80 lacrimal systems, we showed that the FDT is a sensitive (90%) and specific (100%) test in aiding the diagnosis of nasolacrimal obstruction in infants. In the main study, we examined 288 eyes of 232 children with epiphora. The FDT was abnormal in 237 (82%). Of the remaining 51 eyes, there was a clinical explanation for this in 33 cases (epiblepharon, conjunctivitis, etc). We have found that this simple and reliable test taken in conjunction with clinical examination provides an objective assessment of the lacrimal outflow status of young children. PMID- 1757853 TI - Bilateral Brown syndrome in three siblings. AB - The vast majority of cases of Brown syndrome are considered to be of a nonfamilial, sporadic nature. Documented instances of familial transmission are rare. All three siblings in one family pedigree showed bilateral Brown syndrome. Other family members were reportedly unaffected. The current cases, along with previous reports, support the concept that a subset of congenital Brown syndrome may have a strong hereditary basis, being transmitted either as an autosomal recessive genetic trait or an autosomal dominant disorder with decreased penetrance. PMID- 1757854 TI - Brown syndrome associated with contralateral superior oblique palsy: a case report. PMID- 1757855 TI - Visual fields in 4- to 10-year-old children using Goldmann and double-arc perimeters. AB - We report the comparison of field extent measured using two kinetic perimeters: 1) a double-arc perimeter developed by van Hof-van Duin for use in infants and young children, and 2) the standard Goldmann apparatus. Targets used were the V-4 e target on the Goldmann and both 2- and 6-degree targets on the double-arc perimeter. Visual fields were measured by assessing looking responses toward targets presented in a pseudorandom order at 45 degrees, 135 degrees, 225 degrees, and 315 degrees. Fifty-six children (mean age: 6.8 years, range: 4 to 10 years) were tested, with retests undertaken in 20%. The extent of total field size was highly correlated among the three tests (P less than .001) and test retest reliability was high for all three targets (P less than .001). Our previous observation of continued growth with age in visual field extent using the 6-degree target in 4- to 10-year-old children was confirmed and also seen with the 2-degree target in arc perimetry and with the V-4-e in the Goldmann apparatus. Kinetic perimetry using a double-arc perimeter with 2- and 6-degree target sizes appears reliable and comparable, in the four meridia tested, to conventional kinetic perimetry techniques in 4- to 10-year-old children. PMID- 1757856 TI - Combined hamartoma of the retina and retinal pigment epithelium in a patient with neurofibromatosis type 2. AB - We describe a young patient with combined hamartoma of the retina and retinal pigment epithelium who developed bilateral acoustic neuromas and meningiomas of the cervical-medullary junction and fifth cranial nerve. This case illustrates the association between combined hamartoma of the retina and retinal pigment epithelium and neurofibromatosis type 2. The authors recommend that children with a combined hamartoma of the retina and retinal pigment epithelium be screened for neurofibromatosis type 2. PMID- 1757857 TI - Preferential looking and recognition acuities in clinical amblyopia. AB - Although others have noted a correlation between grating and recognition acuities (RA) when both tests are performed on the same day, the value of preferential looking (PL) in predicting eventual visual outcome has not been studied. PL acuities of 64 preverbal patients considered at risk of amblyopia were measured. When these children became verbal, their visual acuities were determined using standard recognition acuity tests. Based on intervening amblyopia treatment between PL and RA measures, 40 patients were designated the minimal treatment group (MTG) and 24 the intensive treatment group (ITG). Chi-square analysis for the MTG showed agreement (P less than .005) between PL and RA in identifying better, equal, and worse eyes. Interocular ratios of PL and RA were significantly correlated for the MTG (P less than .001), but not for the ITG. Monocularly, a consistent correlation between PL and RA was not found. Our data suggest that PL is predictive of recognition acuity in patients whose visual acuity was expected to remain stable. PMID- 1757858 TI - Occult Duane syndrome: co-contraction revealed following strabismus surgery. AB - Three patients presented in infancy with large angle esotropia and limited abduction. Narrowing of the lid fissures with globe retraction on horizontal gaze became apparent only after recession of the medial recti. Abduction remained limited. Two of the three exhibited dissociated vertical deviations, and seemed to have both congenital esotropia and Duane syndrome. The third had an unusual pattern of apparent co-contraction in which the eye attempting abduction actually adducted. Although rare, Duane syndrome may occur in children with large angle esotropia, and its presence may not be revealed until after strabismus surgery. PMID- 1757859 TI - Laser treatment of eye disorders in children. AB - The increasing range of indications for laser treatment and the development of new modalities of lasering have led to a growing tendency to extend this type of treatment to the pediatric population. Problems of compliance in this age group often necessitate the use of general anesthesia. This report describes the operative technique used in 11 children (13 eyes) under the age of 13 years, all of whom underwent laser treatment under general anesthesia for a variety of ocular conditions. Argon or krypton laser photocoagulation was performed in eight children (10 eyes), seven of whom were treated for various retinal pathologies and one for an iris cyst. The other three children underwent Nd:YAG posterior capsulotomy for secondary cataract. PMID- 1757860 TI - Lesions simulating retinoblastoma. AB - Of 500 consecutive patients referred to the Ocular Oncology Service at Wills Eye Hospital with the diagnosis of possible retinoblastoma, 288 (58%) were found on clinical evaluation to have retinoblastoma and 212 (42%) had lesions that simulated retinoblastoma. A total of 23 different conditions accounted for the 212 pseudoretinoblastomas. Three most common pseudoretinoblastomas were: persistent hyperplastic primary vitreous (28%), Coats' disease (16%), and presumed ocular toxocariasis (16%). Congenital cataract and retinopathy of prematurity accounted for a much lower percent of pseudoretinoblastomas in this series as compared to a previously reported series. The pertinent clinical features that serve to differentiate these simulating lesions from retinoblastoma are reviewed. PMID- 1757861 TI - Treatment of acute dacryocystitis in neonates. AB - Twenty-five newborns with acute dacryocystitis underwent probing of the nasolacrimal duct. All had a resolution of the acute dacryocystitis. Only one continued to have epiphora and had to undergo a subsequent probing with silicone intubation at 9 months of age. All were probed without anesthesia, being mummified and held by nurses while the author performed the probing. Only five were treated with parenteral and topical antibiotics for a week prior to probing while 20 were probed without any prior antibiotic therapy. Additionally, five of six mucoceles of the lacrimal sac which did not resolve in the 1st 2 weeks of life with massage were successfully probed without anesthesia. Four of the five mucoceles had developed an acute dacryocystitis on conservative management. Probing of the nasolacrimal duct in the newborn period is a safe and successful approach for acute dacryocystitis. It is a highly successful procedure for the treatment of acute dacryocystitis with a very low morbidity rate. PMID- 1757862 TI - Visual loss in patients with craniofacial synostosis. AB - We reviewed the ocular findings in patients with cranial stenosis, who were seen in the Craniofacial Clinic at The Children's Hospital of Philadelphia, to determine the prevalence, pattern, and etiology of visual loss. There were 15 patients with Apert syndrome, 25 patients with Crouzon syndrome, and 18 patients with other forms of craniofacial synostoses. Visual loss occurred in 17 eyes of 11 patients with Apert syndrome, 14 eyes of 11 patients with Crouzon syndrome, and 12 eyes of 8 patients with other craniofacial synostosis syndromes. Refractive errors and strabismus were present in the majority of these patients. Amblyopia due to strabismus, ametropia, or ptosis was the major reason for visual loss in all three groups of patients. Structural abnormalities contributed to loss of vision in six eyes. PMID- 1757863 TI - Epibulbar squamous cell carcinomas in brothers with Xeroderma pigmentosa. AB - We report two brothers aged 6.6 and 5 years old with the De Sanctis-Cacchione variant of Xeroderma Pigmentosa. They had typically severe skin, and ocular and neurologic involvement. Both had epibulbar squamous cell carcinomas. The oldest presented with a large, invasive, epibulbar mass of the left eye which required enucleation. He also had an invasive squamous cell carcinoma of the right lower lid. The younger brother presented with a smaller papillomatous lesion at the medial limbus of the right eye. After removal, this was found to be squamous cell carcinoma in-situ. Flow cytometry done on the tumors revealed diploidy. The case descriptions, histopathology, and discussion of ocular manifestations are presented. PMID- 1757864 TI - Ocular fireworks injuries in children. AB - Fourteen children and six adults presented in 1987 with firework-induced ocular injuries following celebrations of the Prophet Muhammad's birthday in Tripoli, Libya. The children's injuries were, typically, much more severe than those of the adults. Indigenous modifications to the fireworks, which are intended for children's use, render the devices into very dangerous missiles that, in the cases presented, resulted in the loss of one eye and serious damage to another. Educating children of the proper use of legal fireworks, and parents discouraging their children from modifying fireworks should help reduce the incidence of these severe ocular injuries. PMID- 1757865 TI - Rat bite--an unusual cause of direct trauma to the globe. PMID- 1757866 TI - Relationship between ocular functions and reading achievement. PMID- 1757867 TI - Clinical use of the five-factor model: an introduction. AB - In the past decade, clinical psychologists have developed a renewed appreciation of the value of assessment. At the same time, personality psychologists have come to agree on a fundamental taxonomy of personality traits, the five-factor model. Articles in this special series describe the model and its measurement and discuss applications in three different settings: general clinical practice, a sexual behaviors consultation unit, and a behavioral medicine clinic. This introduction raises questions about the use of personality profiles in psychodiagnosis, the range of applicability of the five-factor model, the utility of personality feedback in psychotherapy, the stability of personality scores among psychotherapy patients, and the feasibility of using personality scores to select optimal forms of treatment. This special series is intended to stimulate research on such topics. PMID- 1757868 TI - The five-factor model and its assessment in clinical settings. AB - Personality researchers have recently converged on the five-factor model as an adequate representation of the structure of personality traits. This article introduces the factors and the NEO Personality Inventory (NEO-PI), a questionnaire designed to measure the factors and some of the traits that define them. Data on the comprehensiveness of the model and on the reliability, validity, and stability of measures of the factors are reviewed, and correlations between scales from the NEO-PI and two instruments widely used in clinical practice (the Minnesota Multiphasic Personality Inventory [MMPI] and the Millon Clinical Multiaxial Inventory [MCMI]) are used to illustrate similarities and differences between normal and clinical assessment. Some issues regarding the clinical use of the five-factor model are discussed. PMID- 1757869 TI - The psychotherapeutic utility of the five-factor model of personality: a clinician's experience. AB - This article summarizes experience using the five-factor model of personality, operationalized by the NEO Personality Inventory (NEO-PI), to facilitate psychotherapy treatment with 119 private-practice, outpatient, psychotherapy patients and their family members over a period of 2 years. Trait theories such as the five-factor model implicitly challenge the premises of much clinical theory, yet they can be useful to clinicians, as they provide a detailed, accurate portrait of the client's needs, feelings, proximate motives, and interpersonal style. I suggest that: Neuroticism (N) influences the intensity and duration of the patient's distress, Extraversion (E) influences the patient's enthusiasm for treatment, Openness (O) influences the patient's reactions to the therapist's interventions, Agreeableness (A) influences the patient's reaction to the person of the therapist, and Conscientiousness (C) influences the patient's willingness to do the work of psychotherapy. Fundamental questions raised by the five-factor model about the nature of psychopathology and psychotherapy are discussed. PMID- 1757870 TI - A comparison of five-factor personality dimensions in males with sexual dysfunction and males with paraphilia. AB - We compared personality profiles of men with sexual dysfunction (n = 51) to those of age-matched men with a primary diagnosis of paraphilia (n = 51) employing the NEO Personality Inventory (NEO-PI), a measure of the five-factor model. Preliminary analyses in a large sample of patients in a sexual behaviors consultation unit supported the reliability and factorial validity of the NEO-PI for this population. Analysis of variance showed significant differences between the dysfunctional and the paraphilic groups on two of the five NEO-PI domains, Neuroticism (N) and Agreeableness (A). The group personality profile of the sexually dysfunctional men was comparable to the normative sample of the NEO-PI, except for a slight elevation in N. By contrast, men with paraphilia had a personality profile marked by high N, low A, and low Conscientiousness (C). Treatment implications of the average personality profile of the sexual dysfunction group and the distinctive personality profile of paraphilic men are discussed. PMID- 1757871 TI - Self-reports, spouse ratings, and psychophysiological assessment in a behavioral medicine program: an application of the five-factor model. AB - This article describes the integration of the five-factor model into assessment procedures used with 109 patients in an outpatient behavioral medicine program. The population, program, assessment techniques, and general findings are explored. A case history involving a psychophysiological disorder is utilized to demonstrate the utility of a taxonomy of personality traits. The NEO-PI, a five factor instrument, is integrated with other assessment techniques to assist in diagnosis, rapport building with the patient, tailoring treatment techniques and goals to the individual's intrapersonal and interpersonal dynamics, and predicting relative success and compliance with noninvasive self-regulation procedures and psychotherapy. PMID- 1757872 TI - Rorschach Depression indices with children and adolescents: concurrent validity findings. AB - Exner (1983, 1986) developed and recently revised (1990b) a Rorschach Depression Index based on scores from variables in the Comprehensive System. This study evaluated both the original and the revised DEPIs for child and adolescent outpatient (n = 67) and inpatient (n = 99) samples in order to assess the diagnostic utility of these indices. There were no significant relationships between the original form and the revised form of the DEPI and clinical elevations on the Depression scale of the Personality Inventory for Children in the outpatient sample or treatment team diagnostic judgments in the inpatient sample. These findings sound a strong cautionary note for using only Rorschach Depression indices to diagnose depression in children and adolescents. PMID- 1757873 TI - Changes in human figure drawings during intensive treatment. AB - This article examines change in the human figure drawings (HFDs) of 32 seriously disturbed young adults during the course of intensive inpatient treatment. HFDs drawn at the time of admission were compared with HFDs obtained more than 1 year after intensive treatment began; both sets were scored on the Goodenough-Harris Scale (GH) and the Robins Balance-Tilt Scale (RBT). The findings indicate that the HFDs significantly improved over the course of treatment, but only for those patients judged introjective, not anaclitic. These findings are consistent with prior research on the same population that were based on analyses of clinical case records and Rorschach protocols (Blatt, Ford, Berman, Cook, & Meyer, 1988). Significant change in the HFDs over the course of treatment suggests that the HFDs provide a unique and independent dimension for assessing therapeutic change. PMID- 1757874 TI - Hopelessness in community-residing aged persons: a viable construct? AB - Previous work with the Geriatric Hopelessness Scale (GHS; Fry, 1984, 1986) suggests that it may be a useful measure of pessimism for a variety of domains among elderly persons. One hundred seven community-residing aged persons were individually administered the GHS and a variety of personality and cognitive functioning measures in an effort to further refine and validate the GHS. Results suggest very modest internal consistency and a poorly defined factor structure for the GHS, in contrast to earlier findings. Although the GHS failed to differentiate elderly persons by age, it was nonetheless related to self-esteem, depression, self-rated health, internality, morale, and life satisfaction. Taken together, these data indicate that the research and clinical utility of the GHS with community-residing aged persons may be more limited than previously believed. PMID- 1757875 TI - An inventory of social skills. AB - A social skills inventory of 128 true-false items was constructed to assess eight hypothesized bipolar dimensions. In a series of principal component analyses, seven of the constructs plus an added concept were isolated in both college and high school men and women. Some of the factors isolated were Social Assertiveness, Directiveness, Defense of Rights, Confidence, and Empathy. Two higher order factors-Social Skill and Empathy-were also identified in several samples. Validity studies revealed strong commonalities with Riggio's (1986) Social Skills Inventory, the Horowitz Inventory of Interpersonal Problems, the Watson and Friend (1969) Social Avoidance and Distress Scale, and a set of self ratings. These findings suggest that the Social Relations Survey (SRS) is a useful device for clinical and research application to problems involving social skills. PMID- 1757876 TI - Development of a self-theory and measurement scale. AB - In this study, we examined a theoretical model of self-development and a scale to measure 12 aspects of the self. The theory, called developmental self-theory, proposes a hierarchical arrangement of dimensions of the self. The 12 scales are collectively called the Omnibus Self-Test and measure Self-Esteem, Positive Self Regard, Moral Self-Concept, Self-Confidence, Self-Reliance, Self-Control, Selfishness, Self-Disclosure, Self-as-Agent, Self-Critical, Self-Identity, and Self-Reflection. Preliminary data on the reliability and validity of the Omnibus Self-Test is reported along with intercorrelations among the scales. PMID- 1757877 TI - [The contribution of hydrophobic parameter to the study of structure activity relationships. II. Antifungal activity of benzylidene-pyrrols]. AB - The purpose of the present work is the contribution of hydrophobic fragmental constant, molecular connectivity and parachor in the study of the relationship between chemical structure and biological activity. The results obtained in this series of benzylidenes-pyrrols have shown high correlation between these parameters and the antifungal activity of these compounds. PMID- 1757879 TI - [Detoxification of aflatoxin B1 by different chemical methods and evaluation of the effectiveness of the treatments applied]. AB - Different chemical treatments were applied to solutions of Aflatoxin B1 in order to compare their efficacy for the detoxification of AfB1: sodium sulfite, sodium hydrogen sulfate, sodium hydroxide, ammonia, sodium hypochlorite, hydrogen peroxide. The rate of the detoxification of AfB1 has been followed by three experimental approaches: 1. Quantitative estimation of the unmodified AfB1 by HPLC chromatography. 2. Quantitative estimation of the most toxic metabolite. AfB1-epoxide by chemical transformation into the trishydroxy AfB1 derivative followed by HPLC analysis. 3. Determination of the bacterial mutagenic activity, following the Ames' test. Among the different detoxification methods that were compared, the treatment with sodium sulfite proved to be the most efficient and seems thus to be recommended for foods contaminated by AfB1. PMID- 1757878 TI - [Valeriana officinalis and Crataegus oxyacantha: toxicity from repeated administration and pharmacologic investigations]. AB - The aim of this work is to study the toxicity of Valeriana officinalis and Crataegus oxyacantha after reiterated administrations. The study has been carried on the rat which received 300 and 600 mg/kg/24 h of the drugs for 30 days. During the period of the treatment, animals weight and blood pressure have been measured. On the end of the treatment the animals have been sacrificed. The principal organs have been weighed and in blood samples collected hematological and biochemical parameters have been determined. This work is concerned by pharmacological properties which are related to the two plants. The influence of the drugs on the behaviour, the pain, the intestinal peristalsis and strychnine convulsions are reported. PMID- 1757880 TI - [The nutritional importance and physiopathology of molybdenum in man]. AB - Molybdenum is an essential trace element taking part in the active site of three human enzymes: xanthine oxidase, aldehyde oxidase and sulfite oxidase, playing a role in the detoxification of the organism and/or the production of important intermediary products. The perturbation of the first two enzymes has no established clinical consequence, but a decrease in activity of the third one is harmful for the organism, particularly the nervous system during pre- or post natal development. The anomalies in the function of these enzymes are generally inherited and linked to the impaired production of the molybdenum cofactor, an organic molecule complexed to the element in the active site. However, several pathological cases in animals and one case in man have been clearly attributed to molybdenum deficiency. It is the reason why molybdenum supplementation has been recommended in long term total parenteral nutrition in infants and adults. PMID- 1757881 TI - [Cell cultures. Complementary or alternative methods to animal experimentation]. AB - In vitro methods, which appeared at the beginning of the century, have had exponential development since one decade for ethical and technological reasons. They can be used for studies concerning intracellular, intercellular or environmental activities. Despite of limiting factors, these techniques offer certain advantages which have to be optimized in order to be validated. They are actually complementary, used for exploratory purposes. In the future, they could replace partially but not completely some in vivo experiments. PMID- 1757882 TI - [Collagen and its technological possibilities]. AB - Collagen enjoys a privileged position as a biomaterial in its cosmetic applications. It exists under different forms and is more particularly able to reticulate. The process which is used allows a modulated reticulation. This means that a collagenous matrix having a varying degree of solubility can be obtained, which can lend itself to different applications. The prilling technique consists in producing microspheres consisting of a more or less reticulated collagenous matrix being able or not to imprison an insoluble or lipophilic active substance having previously been incorporated in the original solution. In this way, it is possible to obtain either strongly reticulated and mechanically resistant microspheres of particles which dissolve when crushed. The cosmetic significance of these new products is connected with the biocompatibility characteristics of the collagenous material and with the characteristics relating to the modulated reticulation of the obtained product. PMID- 1757883 TI - [Reactions and interactions of drugs]. PMID- 1757884 TI - Photoreceptor cell specific proteins of snake pineal. AB - The pineal body of lower vertebrates is saccular and directly photoreceptive. The pineal gland of mammals is parenchymal and not directly photoreceptive. The parenchymal morphology of snake pineal raises questions of direct photoreceptivity of snake pineal and of correspondence of molecular homology with morphological homology. S-antigen and rhodopsin are highly conserved photoreceptor cell specific proteins. We used site-specific monoclonal antibodies (MAb) to study S-antigen and rhodopsin of snake pineal. Immunohistochemical reactivity of snake retina and pineal was compared to that of trout, guinea pig, and rat. MAb's to S-antigen reacted with each pineal and retina tested, but reactivity of individual MAb's with snake tissue was more similar to that with trout than with rat or guinea pig tissue. MAb's to rhodopsin did not react with snake pineal, although they did react with the photoreceptive trout pineal body. MAb's to rhodopsin reacted with retina of each species. These results suggest that although snake pineal is morphologically similar to mammalian pineal, and like mammalian pineal is probably not directly photoreceptive, it does have S antigen homology with lower vertebrates such as trout. PMID- 1757885 TI - Circadian patterns of melatonin, corticosterone, and progesterone in male rats subjected to chronic stress: effect of constant illumination. AB - Plasma and pineal melatonin and plasma corticosterone and progesterone concentrations have been shown to be altered by several types of stressors. This study was designed to define the circadian patterns of the hormones mentioned above in rats subjected to chronic stress and to investigate the influence of constant illumination. The results revealed that melatonin and corticosterone circadian patterns deteriorated and their plasma concentrations were significantly elevated. The constant illumination (2,500 lux) during the dark period (from 2000 to 0600) was not able to suppress melatonin production in stressed animals, while the plasma content of corticosterone was decreased at the end of experimental period compared to control rats. Plasma levels of progesterone were increased in stressed animals as well. Constant illumination, however, provoked also an increase of progesterone secretion in controls. Statistical comparisons between hormonal secretory patterns showed that melatonin and corticosterone correlated negatively in controls (r = -0.58, P less than 0.05) during the nighttime. However, in stressed animals correlation was observed only between melatonin and progesterone secretion during the light and dark period (r = -0.43, P less than 0.05). Surprisingly, the correlation during the nighttime in rats subjected to constant illumination was negative (r = -0.60, P less than 0.02) compared to positive correlation (r = 0.60, P less than 0.02) in rats kept under normal lighting regimen. These results suggest that melatonin release is affected by stress and, possibly, under these circumstances, interacts with adrenal steroid secretion. PMID- 1757886 TI - Circadian rhythms of plasma melatonin in the Adelie penguin (Pygoscelis adeliae) in constant dim light and artificial photoperiods. AB - The response of plasma melatonin in Adelie penguins (Pygoscelis adeliae) to constant dim light and to light/dark cycles was measured to determine the capacity of the pineal gland to secrete melatonin after exposure to continuous daylight for 2 months. Penguins were moved in mid-summer from the natural photoperiod to either constant dim light (n = 10), to a 12L:12D light/dark cycle (n = 5), or to a 12L:12D light/dark cycle with a 30 min light pulse (50-155 lux) on the third (n = 4) or sixth (n = 5) "night." Blood samples were collected regularly through cannulae for up to 33 h. The birds in dim light were sampled after 2 days, with samples obtained over at least 24 h from 7 birds. Three of these birds had melatonin rhythms (peak levels 66.7-130.2 pg/ml) whereas the other 4 birds had constant low levels (less than 44 pg/ml). The phase of the rhythm was similar for all 3 birds. This is consistent with the pacemaker that regulates the circadian rhythm of melatonin secretion being entrained to a period of 24 h when the penguins were exposed to the natural photoperiod. Mean melatonin levels (42.7 +/- 2.5 pg/ml) were elevated compared to those previously reported in penguins under natural daylight. All penguins held under a 12L:12D light/dark cycle had melatonin rhythms. The phase and form of these rhythms were similar to those reported for other birds, and they appeared to be circadian rhythms entrained by the light/dark cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757887 TI - No difference in day-night serum melatonin concentration after pineal grafting into the third cerebral ventricle of pinealectomized rats. AB - Serum melatonin concentration and its day-night difference in pinealectomized, stereotaxically grafted rats with pineal transplants was examined. The nighttime serum melatonin concentration increased significantly only in pinealectomized rats that received two pineal transplants. In neither pinealectomized rats receiving two pineal glands and one cotransplant of superior cervical sympathetic ganglion nor pinealectomized-ganglionectomized rats receiving two pineal transplants was there a demonstrable increased in serum melatonin concentration. Although some pineal transplanted hosts demonstrated increases in serum melatonin concentration, there was no day-night variation in serum melatonin concentration. This may be due to a number of mitigating factors. Pineal grafts may not receive the appropriate functional reinnervation from the host brain due to the location of the transplantation in the cerebral ventricle or due to lack of sufficient time for the growth of invading host neurites. PMID- 1757888 TI - Pineal rhythm of N-acetyltransferase activity and melatonin in the male badger, Meles meles L, under natural daylight: relationship with the photoperiod. AB - The rhythmicity of melatonin secretion and of pineal NAT activity was compared in male badger kept in natural daylight during two distinctly different photoperiods (January and June). The hormone and its enzyme follow the same pattern with a nighttime elevation and a low level during the day, demonstrating the presence of a nyctohemeral rhythm. The high correlation found between the NAT activity and the melatonin concentration suggests that NAT is the rate-limiting enzyme in melatonin synthesis in the badger. Peak amplitudes were similar under the two photoperiods. Melatonin secretion occurred in the first part of the night irrespective of the photoperiod. The rhythm of melatonin secretion is modified by the photoperiod. The duration of high nighttime levels varies; it is longer (8 h) when the night is long (16 h) in January, and shorter (6 h) when the night is short (8 h) in June. In the badger, differences in the duration of high level melatonin at night may reflect variations in day length and convey to the animal the photoperiodic information. PMID- 1757889 TI - Daily cycles of putrescine, spermidine, and spermine in the liver, pineal gland, harderian gland, anterior pituitary, and testes of rats kept in LD 12:12. AB - A circadian rhythm in cellular polyamine levels was detected in the liver, pineal gland, anterior pituitary gland, Harderian gland, and testicular seminiferous tubules of male rats fed ad libitum and maintained in a light:dark cycle of LD 12:12 (lights on at 07:00). Liver putrescine content was highest at 24:00, showing a sixfold increase over 12:00 levels. Pineal spermidine and spermine contents reached a maximum at 06:00, late in the dark phase. A similar pattern was also detected in the Harderian gland. In the anterior pituitary, the polyamines putrescine, spermidine and spermine were highest at 18:00, late in the light phase. However, the increase in putrescine was not statistically significant. The three polyamine contents decreased late in the dark phase. In testicular seminiferous tubules putrescine, on the contrary, was highest (about a twofold increase) late in the dark phase. PMID- 1757890 TI - Pineal melatonin concentrations during day and night in the adult hedgehog: effect of a light pulse at night and superior cervical ganglionectomy. AB - The European hedgehog (Erinaceus europaeus L.) is a hibernating mammal and seasonal breeder in which numerous circadian and circannual rhythms are entrained and synchronized by photoperiod. The present study was undertaken in order to establish the involvement of the pineal gland in transducing the photoperiodic message in this species. Pineal melatonin concentrations were determined by radioimmunoassay in female hedgehogs kept under natural climatic conditions and killed during the light:dark (L:D) cycle in spring and autumn, after the interruption of darkness by a 45 min light pulse, and after bilateral superior cervical ganglionectomy (SCGx). Absolute melatonin concentrations were low (less than 100 pg/pineal) in the pineal gland. Under natural climatic conditions, in spring and in autumn, pineal melatonin concentrations exhibited a marked diurnal rhythmicity, with very low levels in the day (1200: less than 10 pg/pineal) and high levels during the night (2200: 71.9 +/- 18.6 pg/pineal; 0200: 42.5 +/- 15.6 pg/pineal). The 45 min light pulse during darkness depressed rapidly and significantly the melatonin content (dark + light [D + L]: less than 10 pg/pineal), but a subsequent return to darkness restored high melatonin content after approximately 2 h (D + L + D: 65.4 +/- 20.2 pg/pineal). After bilateral SCGx, melatonin concentrations were reduced and no increase during night could be observed, either in animals sacrificed 42 days after SCGx or in animals killed 2 years after SCGx. In the hedgehog, as in other mammals, pineal melatonin concentrations are related to the light:dark cycle. Such data indicate that during the year, in this species, the effects of light on seasonal endocrine rhythms may be mediated by the pineal gland. PMID- 1757891 TI - Central pattern generators: some principles learned from invertebrate model systems. AB - 1. Central pattern generators (CPGs) underlie a wide variety of rhythmic behaviours such as locomotion and respiration in most multi-cellular organisms. 2. The CPG's are capable of generating a patterned output without phasic sensory input. 3. The organization of the CPG is due to both intrinsic properties of the individual neurons and their network interactions. 4. To gain an understanding of the mechanisms which underlie rhythmicity a CPG has been reconstructed in culture. This will allow investigators to test directly the mechanisms underlying the generation of rhythmic output and will allow the direct testing of the mechanisms by which various modulators affect the CPG. PMID- 1757892 TI - Repetitive impulse activity potentiates spontaneous acetylcholine secretion at developing neuromuscular synapses. AB - The effects of presynaptic impulse activity on the transmitter secretion at developing neuromuscular junctions were examined in Xenopus nerve-muscle cultures. Repetitive suprathreshold stimulation of the presynaptic neuron results in marked potentiation of spontaneous synaptic activity, as shown by whole-cell voltage-clamp recording of synaptic currents in the postsynaptic muscle cell. Our results are consistent with the notion that synaptic efficacy of the developing synapse is potentiated by the presence of electrical activity. Such activity dependent synaptic modulation enables the early neuronal activity to play a regulatory role during the maturation of synaptic connections. PMID- 1757893 TI - Endocytosis of the synaptic vesicle protein, synaptophysin, requires the COOH terminal tail. AB - Synaptic vesicles participate in a cycle of fusion with the plasma membrane and reformation by endocytosis. Endocytosis of membrane proteins by the well studied clathrin-coated vesicle pathway has been shown to involve specific sequences within the cytoplasmic tail domain. Proteins taken up by clathrin-coated vesicles are directed to early endosomes from which they may return to plasma membrane. Recent evidence suggests that the synaptic vesicle protein synaptophysin is targeted to early endosomes in transfected fibroblasts and in neuroendocrine cells. To begin to test whether sequences within the COOH-cytoplasmic domain are required for internalization we have expressed a synaptophysin molecule lacking this domain in 3T3 cells and measured its rate of internalization. While a full length synaptophysin was internalized efficiently, we could not detect internalization of the mutant construct. These data are consistent with a model in which the COOH-terminal tail is required for coated-pit localization and hence targeting of synaptophysin to early endosomes. PMID- 1757894 TI - Examining personal control beliefs as a mediating variable in the health-damaging behavior of substance use: an alternative approach. AB - Substance use continues to be a concern for researchers and health professionals alike. One of the most extensive areas of research on health-related behaviors such as smoking and drug use has been on personal control beliefs. Since many health actions (both facilitative and deleterious) depend on voluntary behaviors, and many health-related prevention and intervention programs are predicted on an assumption of controllability, this is an important area to consider. This article is a review of some of the literature and presents an alternative approach that entails using area-specific and domain-specific methods to examine the role that control beliefs play in the health-damaging behavior of substance use. PMID- 1757895 TI - Perceptions of submissiveness: implications for victimization. AB - Some researchers have suggested that a precondition of affective submissiveness may increase the likelihood of female victimization in sexual assault, whereas others have suggested that criminal offenders use perceptions of vulnerability when selecting a victim. In this study, based on American college students, men (decoders) rated videotaped women (encoders) dominant versus submissive using a semantic differential instrument. Cue evaluators analyzed the body language and appearance of the videotaped women using a Likert instrument. The results suggest that (a) men form differentiated perceptions of dominant versus submissive women, (b) such perceptions substantially rely on nonverbal cues, (c) dominant and submissive women display visually different behaviors and appearances, and (d) men tend to select submissive females for exploitation. PMID- 1757896 TI - Stress and context in auditory word recognition. AB - Recent work in psycholinguistics has revealed that the role of lexical stress in auditory word recognition may be a complex one involving other potential sources of information. In the present investigation, the nature of lexical stress effects on auditory word recognition in context is examined. The ability of subjects to identify words based on the prosodic pattern of the word is examined for the words in isolation and in a sentence context. The results revealed a small influence of stress on the identification of the stimulus waveforms relative to a large effect of context. The data indicate that lexical stress is used in the identification of the words; however, its role is minor compared to the importance of contextual information. PMID- 1757897 TI - Promoting public/academic linkage. AB - 1. Collaborative linkages between public mental health/mental retardation service systems and academic institutions have evolved in response to several problems: increasing numbers of individuals requiring long-term mental health care; the nursing shortage; and a decline in enrollment and students graduating from psychiatric mental health nursing programs. 2. Evidence suggests that a public/academic linkage in the form of a multidisciplinary training course in the care of seriously mentally ill patients promotes a recruitment of mental health professionals to work with these patients. 3. The establishment of academic/health care system linkages can enhance client care, expand and improve clinical experiences and education for students, and provide opportunities for collaborative research among clinical staff, faculty members, and graduate students. PMID- 1757898 TI - Assaultive behavior: know the risks. AB - 1. Violence in our society is an increasing national concern, and violence in health-care settings reflects this trend. Assaultive episodes continue to increase in health-care settings due to various cultural, sociological, and political factors. 2. Present administrative and educational solutions to the problems of assault have failed to decrease the incidence and, in fact, may contribute to the increasing number of assaultive episodes. 3. Psychiatric staff can reduce incidence of assault by recognizing the risk factors and designing styles and interventions with these factors in mind. 4. Risks most often associated with assault are history of assault, diagnosis of dementia or organic brain disorder, intoxication from drugs or alcohol, and from the characteristics of the milieu and treatment itself. PMID- 1757899 TI - Psychiatric consultation. Improving the work environment. AB - 1. The consultant initially must negotiate with the leader to clarify the need for and purpose of consultation. 2. Confidentiality is maintained by sharing group data without revealing identities of individual nurses. 3. Recommendations can be given as options from which the group can choose. 4. Consultation is a process using skills of establishing rapport, interviewing, extrapolating themes, and giving feedback. PMID- 1757900 TI - How can we become more aware of culturally specific body language and use this awareness therapeutically? PMID- 1757901 TI - Assault's other side. PMID- 1757902 TI - Target weight procedure: preventing water intoxication. AB - 1. Prevention of water intoxication depends on early intervention for polydipsic patients who seem to be retaining fluid. The Target Weight Procedure is designed to detect early signs of fluid retention by means of weight gain and low sodium levels. 2. The use of this protocol, in addition to successfully decreasing the number of acute water intoxication episodes, has also led to increased awareness of the meaning of patient behavior, an increased sense of control of patients with water intoxication over their behavior, and an increased feeling of competence among the staff. 3. The success of the protocol seems to be based on its purpose of identifying patients at risk and those with an impending episode, as well as secondary advantages, for example, giving the patients the option to alter their behavior to be removed from the protocol. PMID- 1757903 TI - Aspiration cytology of the breast with immediate reporting: initial experience with 1000 patients in a district general hospital. AB - A total of 1000 patients with a palpable localized breast mass were assessed clinically at a surgical breast outpatient clinic and fine needle aspiration cytology was performed and immediately reported. This large series was undertaken by one surgeon and one pathologist, neither of whom had any previous experience with such a combined clinic, and the pathologist initially had only minimal experience of breast aspiration cytology. The results show a diagnostic accuracy of 96.9%, a positive predictive value of 98.4%, and a negative predictive value of 95.7%, and indicate that the provision of such a facility in a district general hospital is of benefit in the diagnosis of palpable localized breast lesions. PMID- 1757904 TI - Increasing infantile hypertrophic pyloric stenosis? Experience in an overseas military hospital. AB - Fifty-four children with proven infantile hypertrophic pyloric stenosis (IHPS) were treated by Ramstedt's pyloromyotomy during a 14-year period. Between the years 1986 and 1989 the mean incidence of the disease was noted to have risen by 2.72 per 1000 live births over the preceding 10 years. Statistical analysis confirmed a significant upward trend between the years 1976 and 1989. Analysis of the majority of the cases revealed comparable perioperative morbidity rates with other UK district general hospitals. There was no operative mortality. The character of IHPS in military personnel overseas has more in common with UK than international trends. The incidence in this subgroup may be rising. PMID- 1757905 TI - Partial cholecystectomy in the emergency treatment of acute cholecystitis in the compromised patient. AB - Emergency cholecystectomy in the high-risk patient still results in a substantial mortality and morbidity rate. A prospective experience is presented with partial cholecystectomy in 16 high-risk patients (APACHE II greater than 10) undergoing emergency surgery for perforation, empyema or failure to respond to conservative treatment. Excessive bleeding tendency was present in three patients. One patient died (6%). Mean operative time was 40 min. One patient developed an intra abdominal bile leak due to a retained common bile stone 8 months after operation. Partial cholecystectomy has the advantages of both cholecystectomy and cholecystostomy. It is a fast and safe procedure and should be considered as an option in the emergency situation in the high-risk patient. PMID- 1757906 TI - Curative resection: the major determinant of survival in patients with large bowel cancer. AB - Data collected prospectively from 578 patients with colorectal cancer managed by 12 Manchester surgeons were analysed to evaluate the effects on survival of prognostic, clinical and pathological factors. Available preoperative and perioperative factors were included in a stepwise regression analysis and curative resection was found to be most strongly associated with patient survival. Other variables ranked according to their relative importance were performance status, weight loss and sex. The finding of the study supports the need to establish an early diagnosis if long-term survival results are to improve. PMID- 1757907 TI - Prevention of postoperative renal dysfunction in patients with obstructive jaundice: a comparison of mannitol-induced diuresis and oral sodium taurocholate. AB - The effect of oral sodium taurocholate was compared with that of intravenous mannitol when used independently to determine their relative effect on protecting postoperative renal function in patients with obstructive jaundice. A total of 20 patients with obstructive jaundice were randomized to receive either mannitol or sodium taurocholate before surgery. Their preoperative and postoperative renal function was monitored using serum creatinine and predicted creatinine clearance over a 4-day period. There was no difference in postoperative renal function between the two groups and no patient from either group suffered significant renal dysfunction. PMID- 1757908 TI - Cancer of the ureter in a Negro population. AB - A 13-year retrospective study of ureteric tumours in an African Negro population is reviewed. The tumour is rare. Seven cases were reported, six of them admitting to smoking over 50 packets of cigarettes per year. All the tumours were of the transitional cell type and prognosis is related to grade and staging. Nephroureterectomy with excision of a cuff of bladder was the treatment given. Follow-up was poor owing to illiteracy. PMID- 1757909 TI - Fine needle aspiration biopsy of pulmonary lesions: a 2-year experience in a district general hospital with a literature review. AB - During the 2 years of 1987 and 1988, 74 patients with suspected malignant lung lesions underwent fine needle aspiration biopsy at the Bradford Royal Infirmary. Using a 20Fr needle, sufficient specimen (smear and clot) was obtained in 70 (95%) patients for histological examination. The indications for the procedure were: failure to make a diagnosis at bronchoscopy and bronchial lavage in 32 (43%) patients, peripherally located lesion in 28 (38%) patients, poor anaesthetic risk in 20 (27%) patients, negative bronchoscopy and mediastinostomy in five (7%) patients and three (4%) patients refused operative intervention. There were no deaths and complications were few. Seven patients developed pneumothorax, three of whom required intercostal drainage. Transient haemorrhage as shown by haemoptysis occurred in one patient and one patient complained of pleuritic chest pain. Of the 60 patients with malignant disease eventually proven, 50 were diagnosed correctly. The overall sensitivity and specificity of the test were 81 and 100% respectively based on histological and/or clinical outcome of the lung lesion. The test was cost-effective, diagnostic yield was high and complications were few. The use of fine needle aspiration biopsy as part of the management policy in peripheral lung lesions is realistic in a district general hospital. PMID- 1757910 TI - General surgery with a special interest in vascular surgery: is the tail starting to wag the dog? AB - Most general surgeons are expected to develop an interest in a surgical specialty in addition to their general surgical workload. Over a 2-year period we have prospectively analysed the type of patient admitted to a general surgical unit with a special interest in vascular surgery. Half of the admissions were emergencies, over which we had no control. Of the elective admissions, there was a steady increase in the proportion of patients with a vascular diagnosis. This was due to increasing numbers of arterial reconstructions and interventional radiological procedures being undertaken. As cutbacks are made in the numbers of available beds and operating sessions, the increasing number of patients requiring admission for the management of arterial disease can only be achieved at the cost of patients awaiting routine general surgical procedures. PMID- 1757911 TI - Epidemiology of sharps accidents in general surgery. AB - A prospective study was carried out of all general surgical operations in one theatre of a teaching hospital over a 6-week period to identify the predisposing factors involved in the occurrence of sharps accidents and their relative importance. Although various predisposing factors have been intimated, the relative importance has never been ascertained. Glove puncture was used as an objective measure of a sharps accident and this was compared with subjective reporting of needlestick injury. The overall rate of sharps accidents per surgeon per operation was 23%. The position at the operating table and medical rank of operator affected the rate of accidents more than duration of operation. The group at most risk of sharps accidents was junior surgeons acting as the principal operator. It is important to recommend inoculation against hepatitis B in this group before starting surgical training. Another method of minimizing the risk to junior surgeons would be compulsory training on surgical rigs. Operations on patients with AIDS or hepatitis B should be carried out by the most senior surgeon available to reduce the risk of sharps injury and disease transmission. PMID- 1757912 TI - Needlestick injury in surgeons: what is the incidence? AB - A prospective study by questionnaire was carried out to investigate the incidence of needlestick injury in the operating theatre staff of a teaching hospital and to calculate the individual risk of acquiring blood-borne virus infection in the UK from this source. The individual rate of needlestick injury in operating theatre staff was 1.55% per surgeon per operation (confidence interval (Cl) 0.6 2.5%). The calculated rate of clinical hepatitis B in surgeons compared with the observed rate suggests that needlestick in theatre is the main mode of transmission. PMID- 1757913 TI - Bath scalds in children in the south-east of Scotland. AB - Scalds caused by domestic hot tap water constitute a significant but preventable hazard in childhood. We have reviewed some of the factors contributing to such injuries, and the experience of a regional paediatric burn unit in their treatment. There were 91 children with bath water scalds and 667 children with thermal injuries from other sources included in this study. In the former group, scalds were more common on the limbs, including the hands and feet. Scalds involving over 40% of body surface area were more common in children with bath water injuries; however, there was no difference between the groups with regard to hospital stay or requirement for skin grafting. Parents ran the bath responsible for scald production in most cases, but single parenthood did not appear to be a risk factor. First aid application made no significant difference to eventual burn area or hospital stay. It appears from this study that reduction of domestic hot water temperature is necessary. Statutory control is likely to offer the best solution to the problem of domestic hot tap water scalds in childhood. PMID- 1757914 TI - Methicillin-resistant Staphylococcus aureus in surgical patients: Malaysian experience. AB - Methicillin-resistant Staphylococcus aureus has emerged as an important cause of nosocomial infections in recent years. During 1988 in the Department of Surgery of the University Hospital in Kuala Lumpur, Malaysia, 148 patients were shown to be infected or colonized with these organisms. The patients at risk were those who stay in hospital for greater than 14 days, those over 50 years of age, patients who underwent neurosurgery, cardiothoracic surgery, or were admitted with major burns. Of the 148 patients, 78 (52.7%) were clinically infected, the remaining 70 being colonized. A total of 28 patients died (18.9%) but only five (3.4%) as a direct result of this infection. The estimated annual cost of controlling the organism was found to be approximately MR$250,000. (50,000 pounds). This nosocomial infection therefore represents a serious problem, especially in developing countries where health funding and health facilities are limited. PMID- 1757915 TI - Controlled-tension suture-tying forceps. AB - Suture-tying forceps have been designed to enable surgeons to tie consecutive sutures to the same tension to create an evenly compressed wound. The tensioning effect of the forceps was tested by tying a suture to the end of a cantilever beam strain-gauge device. Three sutures were used: 10/0 nylon, 8/0 polyglactin (Vicryl) and 8/0 virgin silk. The tests were repeated, coating the tips with citrated blood, sodium hyaluronate and saline. Adjustment of the forceps altered the suture tension in 0.015-N steps. Sterilization of the forceps by ethylene oxide or by an autoclave caused no obvious regression in the forceps performance. When the suture and surface lubricant remain constant, there is a linear relationship between forceps setting and the tension induced in the suture. PMID- 1757916 TI - Obscure gastrointestinal bleeding: idiopathic aortoduodenal fistula. PMID- 1757917 TI - Anal leukoplakia: management using a staged plastic procedure. PMID- 1757918 TI - Surgery to the great toe. PMID- 1757919 TI - 'Z' metatarsal osteotomy: modified Mitchell's osteotomy for hallux valgus. AB - The Mitchell's osteotomy is an established and successful operation for hallux valgus. We report a previously undescribed procedure comprising a step or 'Z' osteotomy that is a simplified version of the Mitchell's osteotomy which involves less extensive soft tissue dissection and avoids opening the first metatarsophalangeal (MTP) joint. In total, 51 operations in 40 patients were reviewed with a mean follow-up of 4.7 years. The results were compared with those reported by Mitchell in his paper of 1958, using the same criteria. The mean age was 24 years and 82% of patients were women. In 88% of patients the results were rated excellent or good and there were no serious complications. These results suggest that this procedure is as successful as the Mitchell osteotomy in young patients, and it may have long-term benefits. PMID- 1757920 TI - Surgical decompression of the carpal tunnel using infiltrative anaesthesia: description of technique. PMID- 1757921 TI - Closed rupture of the distal transverse arch of the hand. PMID- 1757922 TI - Rhys-Davies exsanguinator: a previously unreported complication. PMID- 1757923 TI - Prognosis in rheumatoid arthritis. PMID- 1757924 TI - Rheumatoid factors as predictors of rheumatoid arthritis. PMID- 1757925 TI - Rheumatoid factors antedating clinical rheumatoid arthritis. AB - The relationship between rheumatoid factors (RF) and rheumatoid arthritis (RA) was studied in the Mini-Finland Health Survey. This covered a representative sample of the Finnish population over 30 years of age, initially comprising 8,000 persons, of whom 7,217 participated in the field survey carried out in 1978-80. The participants were followed using record linkage with the Social Insurance Institution's population register to identify patients entitled to free medication. Until the end of 1988, 21 persons had developed new seropositive RA. In 15 cases, preillness specimens contained elevated levels (greater than or equal to 20 IU/ml) of RF. In the remaining 6 cases with RF negative preillness specimens, the interval from taking the blood specimen to the onset of disease was 4 years or more. RF represent a key element in the rheumatoid inflammatory process. Their occurrence in preillness specimens suggests that they may have a primary role in the pathogenesis of the disease. PMID- 1757926 TI - Older versus younger onset rheumatoid arthritis: results at onset and after 2 years of a prospective followup study of early rheumatoid arthritis. AB - The influence of age at onset was studied in a prospective followup of early rheumatoid arthritis (RA). Patients greater than or equal to 60 years (n = 71) showed significantly more often an onset in both large and small joints and higher disease activity at the start compared with patients less than 60 years (n = 142). The higher disease activity was still present after 2 years of followup (greater than or equal to 60 years, n = 46, less than 60 years, n = 101); as well, there was a tendency towards more radiographic damage. Rheumatoid factor (RF) and DR4 were comparable in both age groups. Our data show a more severe course in older age RA. This disagreement with the literature is probably due to the fact that many studies are cross sectional with unbalance of RF in the 2 age groups. PMID- 1757927 TI - Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis. AB - We studied clinical and health status measures in 561 patients with rheumatoid arthritis (RA). Two hundred sixty-four patients were seen within 2 years of disease onset and followed for an additional 2 years. Four other groups were each followed for 5 years, and had disease durations of 2-7, 7-12, 12-17, and 17-22 years, respectively, at the first clinic visit. Functional disability developed very early in the course of RA and continued to worsen at about an equal rate over 22 years. Anxiety, pain scores, and self-assessed severity also increased with time, but erythrocyte sedimentation rate (ESR), morning stiffness, and joint counts were unchanged. Treatment resulted in reduction in joint counts and in nonsignificant improvements in ESR, stiffness, and psychological scores. But functional loss increased in each time period in spite of treatment. Variables most effective in controlled clinical trials are not effective as longterm measures of RA outcome. PMID- 1757928 TI - The assessment and prediction of functional disability in rheumatoid arthritis. AB - We assessed functional disability with the Stanford Health Assessment Questionnaire Functional Disability Index (FDI) in 1,274 patients with rheumatoid arthritis (RA) followed longitudinally for up to 12 years. The rate of functional loss increased sharply after the first clinic visit. Half of patients with RA (median survival time) will reach FDI scores of about 1 in 2 years, 2 in 6 years, and 2.5 in 10 years after the first clinic visit, levels that correspond to moderate, severe and very severe loss of functional ability. Functional outcomes may be predicted by simple demographic and clinical assessments, the best of which are self-assessed measures of global severity, pain and function. PMID- 1757929 TI - Mortality predictors among 263 patients with rheumatoid arthritis. AB - A cohort of 263 patients who completed Health Assessment Questionnaires (HAQ) each year from 1981 to 1989 is examined. Forty-three (43) possible covariates measured in 1981 are considered that might help predict mortality over the 8 years of the study. We use univariate correlation coefficients, stepwise regressions, and survival functions to identify a number of covariates that appear useful for predicting survival: age (-), prednisone use (-), disability index (-), male sex (-), never married (-), penicillamine use (+), divorced (+), and no occupation (-). Our results confirm studies suggesting that the HAQ disability index is a useful prognosticator of length of survival. PMID- 1757930 TI - Strength and function in the normal and rheumatoid hand. AB - We have reevaluated the Martin vigorimeter to measure grip strength in healthy subjects, and patients with rheumatoid arthritis (RA), and investigated the correlation of grip strength and hand function using the Jebsen hand function tests and Purdue pegboard test before and after treatment. The vigorimeter showed good test-retest reliability (r greater than 0.911) and interrater reliability (r greater than 0.915). Test-retest reliability was greater than 0.97 for the Jebsen test, and greater than 0.94 for the Purdue test in healthy individuals. Seventeen patients with RA were studied at intervals of 1 to 16 weeks. Active joint count and grip strength both improved significantly. Improvement in grip strength correlated with improvement in active joint count. Hand function tests were significantly impaired in the patients with RA. PMID- 1757931 TI - "Pseudoseptic" arthritis complicating rheumatoid arthritis: a report of six cases. AB - Six cases of a severe, sterile, inflammatory arthritis mimicking septic arthritis occurred in 328 patients with rheumatoid arthritis (RA) over a 4-year period. Four patients were poorly controlled by or had recently discontinued a disease modifying antirheumatic drug. Five improved after receiving increased glucocorticoid therapy. Radiographs showed no accelerated joint destruction after a mean followup of 29.5 months (range 8-49). Recognition of "pseudoseptic" arthritis occurring in the course of RA permits appropriate therapy and avoids extended antibiotic treatment. PMID- 1757932 TI - Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of 191 cases. AB - One hundred and ninety-one patients with severe rheumatoid arthritis (RA) were included in a prospective open longterm study of the safety, efficacy and maintenance of methotrexate (MTX) treatment. The mean duration of MTX treatment was 19 +/- 13.2 (3-58) months; the mean weekly dose of MTX was 10.2 +/- 0.2 mg. Analysis of the 191 patients in an intent-to-treat manner showed a significant improvement of all the clinical variables and a decrease of erythrocyte sedimentation rate with a steroid sparing effect. The probability of continuing MTX therapy for up to 2 years was 65% and for up to 5 years was 46%. Adverse effects of MTX occurred in 37.1% of the patients, but only 15.7% discontinued MTX permanently. PMID- 1757933 TI - Salmonella arizona arthritis and septicemia associated with rattlesnake ingestion by patients with connective tissue diseases. A dangerous complication of folk medicine. AB - Snakes constitute the main reservoir of Salmonella arizona, which are opportunistic pathogens in patients with serious underlying diseases. The 2 may meet when such patients ingest uncooked snake flesh, most often as a folk remedy for arthritis or other conditions. We have seen 11 patients in whom Salmonella arizona infection was documented. Six had systemic lupus erythematosus and another had dermatomyositis and are described in detail. All 7 had received prednisone, which was combined with azathioprine in 3. Five developed septic arthritis, including the site of a hip prosthesis in one patient. A history of dessicated rattlesnake ingestion as a "natural" remedy in either capsule or powder form was obtained in all but one of the 7 patients. Patients often think that if natural or folk remedies are not helpful they also are not harmful and, therefore, safe and worth trying. We disprove that belief and call attention to the perils of one such remedy: dessicated rattlesnake, particularly when ingested by patients with connective tissue diseases who may be immunocompromised. PMID- 1757934 TI - Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease. AB - We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation. PMID- 1757935 TI - Early undifferentiated connective tissue disease. II. The frequency of circulating antinuclear antibodies in patients with early rheumatic diseases. AB - The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM 1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses. PMID- 1757936 TI - Role of lymphocytes in collagen induced arthritis. AB - We investigated the time related changes of lymphocyte subsets in the blood, regional lymph node and thymus during the development of collagen induced arthritis in mice. Flow cytometric analysis showed that Lyt2+ T, but not L3T4+ T cells in the blood or regional lymph node, was significantly reduced throughout the observation. The number of Lyt2+ T cells was decreased in lymph nodes of collagen immunized vs adjuvant controls while B cells were increased and L3T4+ T cells were not different. These might act as a potential factor for the onset of collagen induced arthritis. The reduction of Lyt2+ cells was not influenced by thymic T cell maturation; it is conceivable that the main immune organ is the regional lymph node. PMID- 1757937 TI - Major histocompatibility complex (MHC) complement deficiency, ancestral haplotypes and systemic lupus erythematosus (SLE): C4 deficiency explains some but not all of the influence of the MHC. AB - In 1982 we reported that among Caucasians with systemic lupus erythematosus (SLE) there is an increased frequency of C4A null. As this allele occurs on the HLA A1,B8,BfS, C4AQO,B1,DR3 (8.1) supratype, we suggested this accounted for the reported association of B8 and DR3. Since then we have shown that many supratypes including 8.1 identify unique segments of DNA conserved from a common but remote ancestor. Many of these ancestral haplotypes (AH), including 8.1, carry disease genes and some bear C4 null. We have therefore tested the hypothesis that in SLE C4 null alleles are directly involved by examining (1) whether all or only some AH bearing C4 null alleles are increased, (2) whether C4 null is increased in all racial groups examined, and (3) whether C4 null is associated with the presence of antinuclear antibodies (ANA) in the absence of SLE. We performed HLA and complement allotyping on 62 Australian Caucasians and 9 Australian aborigines with SLE and on the 10 out of 133 healthy individuals with 7 or more international units of ANA. Our data confirm an association of C4A null in Australian Caucasians (gene frequency 0.30 versus 0.15 in controls) and show an increased frequency of C4B null in Australian aborigines (gene frequency 0.33 versus 0.22). A review of an extensive literature shows C4A and/or C4B null are increased in all racial groups examined. On the other hand, the HLA A3,B7,BfS,C4A3,B1,DR2 (7.1) AH rather than C4 null is associated with ANA in health. Our data indicate that while C4 nulls contribute to MHC susceptibility, other genes are likely to be involved. PMID- 1757938 TI - Muscular weakness in systemic lupus erythematosus. AB - We systematically evaluated muscular weakness in a series of patients with systemic lupus erythematosus (SLE) using standardized neurological scoring systems, namely Neuropathy Symptom Score for symptoms, and Neurological Disability Score for signs. Symptoms of weakness were statistically associated with clinical and electrophysiological evidence of nerve and muscle disease. Signs of weakness were statistically associated with malaise, disease activity, anemia, age, and raised erythrocyte sedimentation rate. Various disease associated variables influenced symptoms and signs differently. It is important to define a baseline characterizing muscular weakness in SLE before conclusions are drawn regarding its significance and prevalence. PMID- 1757939 TI - Muscle pathology in ankylosing spondylitis: clinical, enzymatic, electromyographic and histologic correlation. AB - We assessed muscle pathology in 30 patients with ankylosing spondylitis (AS) and 22 controls to assess if skeletal muscle is affected primarily by the inflammatory process of the disease. Investigations included a questionnaire on musculoskeletal discomfort, physical exercises, dynamometric measurements, EMG, and biopsy of the quadriceps muscle. Symptoms of muscular weakness were related with enthesopathic activity index. Plasma CK was higher in patients than in controls. A myopathic EMG pattern was found in 46.4% patients. Histological changes were found in 66% and did not correlate with symptomatology. Patients with AS with clinical muscular manifestations probably have intense enthesopathic inflammatory activity. It is suggested that muscles are secondarily affected as a consequence of pain inhibition and reduced activity. PMID- 1757940 TI - Magnetic resonance imaging of the parotid gland in patients with Sjogren's syndrome. AB - To detect structure and size abnormalities, magnetic resonance imaging (MRI) of the parotid gland was performed on 36 patients with sicca complaints. Twenty-four patients had primary Sjogren's syndrome (SS) without rheumatoid arthritis (RA) or connective tissue disease; 6 had secondary SS associated with RA, whereas in another 6 cases the related disease could not be classified. Characteristic gland size and structural abnormalities were identified in patients with SS and various stages could be established, compared to patients with other parotid gland disorders, as well as healthy persons. MRI provides an accurate noninvasive technique for assessment of xerostomia in patients with SS. PMID- 1757941 TI - Electrodermal and microcirculatory activity in patients with fibromyalgia during baseline, acoustic stimulation and cold pressor tests. AB - The peripheral sympathetic activity was studied in 27 patients with fibromyalgia and 29 healthy controls through simultaneous measurements of electrodermal variables and blood flow at palmar skin sites during baseline, acoustic stimulation, and cold pressor tests. Compared to the controls, the patient group showed a significantly larger overall increase in the skin electrical conductance and less vasoconstriction during acoustic stimulation and cold pressor tests. These findings imply an increased activity of cholinergic and decreased activity of adrenergic components of the peripheral sympathetic nervous system in patients with fibromyalgia. PMID- 1757942 TI - Isokinetic and isometric muscle strength combined with transcutaneous electrical muscle stimulation in primary fibromyalgia syndrome. AB - Twenty women with primary fibromyalgia syndrome and 20 age matched healthy women were investigated. The subjects performed maximum voluntary isokinetic contractions of the right quadriceps in an isokinetic dynamometer. Maximum voluntary isometric contractions of the right quadriceps were performed with superimposed transcutaneous electrical stimulation. The examination protocol was repeated after 1 h of resting. Isokinetic and isometric muscle strength was found to be, respectively, 45% (p = 0.0001) and 44% (p = 0.0001) lower in the patient group compared to the healthy subjects. The frequency of superimposed twitches was 65% in the patient group and 15% in the control group (p = 0.003). Patients with primary fibromyalgia have a lower maximum voluntary muscle strength than expected. The increased presence of superimposed electrically elicited twitches during maximum voluntary contraction indicates submaximal force application in primary fibromyalgia syndrome. PMID- 1757943 TI - Longitudinal analysis of HLA associated risks for iridocyclitis in juvenile rheumatoid arthritis. AB - The risk of iridocyclitis in children with early onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA) has been shown to be associated with certain HLA haplotypes. Our report contains an actuarial analysis, using one-year intervals, of 161 subjects and estimates haplotype specific risks. Individuals who possess the major susceptibility haplotype HLA-DR5 (11) developed eye disease earlier and with a greater frequency than did those with the protective HLA-DR1 haplotype. Highly significant differences were found between the resulting life-table curves for HLA-DR5 and HLA-DR1 positive subjects (p = 0.00003). These time oriented risk estimates may aid clinicians in determining more precisely the probability of iridocyclitis throughout the course of the disease in children with EOPA-JRA. PMID- 1757944 TI - Soluble interleukin-2 receptor in juvenile rheumatoid arthritis. AB - Juvenile rheumatoid arthritis (JRA) is a chronic, relapsing, inflammatory childhood disease characterized by arthritis and systemic inflammation. At present there is no rapid, efficient laboratory method of assessing disease activity and degree of immune activation. We measured serum soluble interleukin 2 receptor (sIL-2R) levels in 85 samples from 72 patients (22 samples from patients with systemic JRA, 34 from polyarticular patients, 29 from pauciarticular patients, of which 10 were HLA-B27 positive). The mean sIL-2R level from patients was 1565 U/ml, which is significantly elevated compared to control values of 594 U/ml (p less than or equal to 0.005). The highest levels were seen in patients with systemic JRA (mean value 2121 U/ml) while the lowest values were seen in HLA B27 positive (+) patients (mean value 899 U/ml). Patients with clinically active disease had significantly elevated levels (mean value 1745 U/ml) compared to patients with inactive disease (mean value 846 U/ml, p less than or equal to 0.01). Highest levels were seen in patients with active systemic JRA (mean value 2419 U/ml) while patients with pauciarticular JRA and B27 + JRA had the lowest sIL-2R levels (1167 and 1045 U/ml, respectively). sIL-2R levels were elevated in all subgroups of clinically active patients compared to controls (p less than or equal to 0.0005). Three of the 4 patients with serial sIL-2R measurements showed falling values during the period of clinical remission. Using regression analysis and likelihood ratio tests, we found a significant correlation between sIL-2R levels and both disease activity and joint count (p less than or equal to 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1757945 TI - Syringomyelia in a patient with rheumatoid subluxation of the cervical spine. AB - A patient with rheumatoid damage of the cervical spine with cervical cord compression, complaining of a typical syringomyelic syndrome is described. Magnetic resonance imaging revealed cord compression due to an upward displacement of the odontoid peg with a mass of pannus behind the dens, and a syrinx cavity extending from C1 to T1. We postulate that this patient's syringomyelia probably represents a complication of cervical rheumatoid arthritis that has not been described. PMID- 1757946 TI - Herpes simplex hepatitis in a patient with psoriatic arthritis taking prednisone and methotrexate. Report and review of the literature. AB - Herpes simplex hepatitis is a rare disease in adults and with high mortality (81%). Most cases are seen in immunocompromised hosts or in the third trimester of pregnancy. A 43-year-old woman with psoriatic arthritis, treated with prednisone and methotrexate (MTX), presented with an acute abdomen and elevated liver enzymes. The diagnosis was made by liver biopsy. MTX was stopped and acyclovir was started. The patient survived. The diagnosis of Herpes simplex should be suspected in immunocompromised hosts and established by liver biopsy and viral cultures. Treatment includes parenteral acyclovir and discontinuation or reduction of immunosuppressive therapy. PMID- 1757947 TI - Hypertension, renal artery stenosis and the "primary" antiphospholipid syndrome. AB - We describe a 35-year-old man with a history of previous deep vein thrombosis who presented with hypertension. Renal investigations revealed failure to excrete contrast medium by the right kidney on intravenous pyelography. Digital subtraction angiography showed an 80% stenosis of the left renal artery. He was antinuclear antibody negative, as well as negative for antibodies to double stranded deoxyribonucleic acid and extractable nuclear antigens. The lupus anticoagulant test and antibodies to cardiolipin were positive. He conforms to a diagnosis of "primary" antiphospholipid syndrome. PMID- 1757948 TI - Avascular necrosis associated with anticardiolipin antibodies. AB - The association between antiphospholipid antibodies (aPL) and venous and arterial thromboses has been well described. However the association between aPL and avascular necrosis has not been widely reported. We report the association of avascular necrosis with the primary anticardiolipin antibody syndrome in a patient with a history of hemiplegic migraine and cerebrovascular infarcts. This phenomenon appears to be secondary to hemostatic abnormalities associated with the presence of aPL. PMID- 1757949 TI - Immunohistological characterization of lymph nodes in two cases of adult onset Still's disease. AB - Although lymphadenopathy occurs in 60% of patients with adult Still's disease, its histopathological pattern has only recently been described. We report on the immunohistological study of a lymph node biopsy and the clinical course of 2 patients with adult Still's disease. The lymph node histology was characterized by a diffuse paracortical expansion with a high content of immunoblasts and plump endothelium venules. Immunohistochemistry using the alkaline phosphatase, antialkaline phosphatase technique showed the mixed B and T cell nature both of proliferating cells and immunoblasts. When antiheavy and light chain reagents were applied, the B cell component became polytypic. Our report stresses the relevance of immunohistological investigation in the diagnostic approach to Still's disease in which histological findings, if taken alone, might be misleading. PMID- 1757950 TI - An unusual case of factitious arthritis. AB - Factitious arthritis is an unusual manifestation of a factitious illness. We report a case of factitious arthritis after the self insertion of needles and fragments of metallic paper clips into the knee joint area. The case illustrates an unusual presentation of Munchausen's syndrome. PMID- 1757951 TI - Colonic ulcerations in Wegener's granulomatosis. PMID- 1757953 TI - The fragile X syndrome. PMID- 1757952 TI - Osteitis condensans ilii and sacroiliitis. PMID- 1757954 TI - Cloning of the gene for the fragile X syndrome: implications for the clinical geneticist. PMID- 1757955 TI - Molecular genetics of fragile X: a cytogenetics viewpoint. Report of the Fifth International Symposium on X Linked Mental Retardation, Strasbourg, France, 12 to 16 August 1991 (organiser Dr J-L Mandel). PMID- 1757956 TI - Fragile X syndrome: genetic localisation by linkage mapping of two microsatellite repeats FRAXAC1 and FRAXAC2 which immediately flank the fragile site. AB - We report the genetic localisation of the fragile site at Xq27.3 associated with fragile X syndrome. The position of the fragile site within the multipoint linkage map was determined using two polymorphic microsatellite AC repeat markers FRAXAC1 and FRAXAC2. These markers were physically located within 10 kilobases and on either side of the p(CCG)n repeat responsible for the fragile site. FRAXAC1 has five alleles with heterozygosity of 44% and is in strong linkage disequilibrium with FRAXAC2 which has eight alleles and a heterozygosity of 71%. No recombination was observed either between these markers in 40 normal CEPH pedigrees or with the fragile X in affected pedigrees. These markers provide the means for accurate diagnosis of the fragile X genotype in families by rapid polymerase chain reaction analysis and were used to position the fragile X within the multipoint map of the X chromosome to a position 3.7 cM distal to DXS297 and 1.2 cM proximal to DXS296. PMID- 1757957 TI - Genotype prediction in the fragile X syndrome. AB - Fragile X positive, mentally retarded males have been shown to have an insertion or amplification of DNA sequences at, or close to, the site of expression of the fragile site. We show here the application of the detection of such changes to the diagnosis of affected males and female carriers and the identification of normal transmitting males. One fragile X negative male with the clinical features of the Martin-Bell syndrome also possesses an inserted/amplified DNA sequence. The implications of these results for screening for the fragile X syndrome are discussed. PMID- 1757958 TI - Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation. AB - We have studied the patterns of mutation and X inactivation in female carriers of a fragile X mutation, to try to correlate them with various phenotypic features. We used a simple assay, which shows simultaneously the size of the mutation, its methylation status, and DNA fragments that represent the normal active and inactive X chromosomes. We have observed an age dependent process, whereby the 'full' fragile X mutation is found preferentially on the inactive X in leucocytes in adult females, but not in younger ones. This phenomenon was not observed in female carriers of a 'premutation', who have little phenotypic expression. Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation. We have also obtained preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations, possibly owing to selection for smaller mutated fragments. If confirmed, the latter phenomenon might account for the known decrease with age of the expression of the fragile site. Our observations suggest that a gene whose expression is affected by the presence of a full mutation (possibly the FMR-1 gene) has a cell autonomous function in leucocytes, leading to a slowly progressive selection for cells where the mutation is on the inactive X chromosome. PMID- 1757959 TI - A single lymphocyte culture for fragile X induction and prometaphase chromosome analysis. AB - A single lymphocyte culture system is described which produces both reliable fragile X expression and elongated chromosomes for prometaphase analysis. This system, which is based on that described by Wheater and Roberts in 1987, involves the deoxycytidine release of a thymidine block. Eight fragile X positive subjects had an average expression level of 26%, with a range of 12% to 45%, using the thymidine/deoxycytidine protocol. This was comparable to the levels obtained in parallel cultures treated with thymidine alone or fluorodeoxyuridine. PMID- 1757960 TI - Ehlers-Danlos syndrome type IV: phenotypic consequences of a splicing mutation in one COL3A1 allele. AB - The features of a child with Ehlers-Danlos syndrome type IV (EDS IV) resulting from a mutation in one COL3A1 allele were studied. The child was heterozygous for a G- to A-transition at the splice donor site of intron 41. It resulted in the splicing out of the exon 41 encoded sequence from alpha 1(III) mRNA and the deletion of 36 amino acids from glycine775 to lysine810 of the triple helical domain of alpha 1(III) chains of type III collagen. The amount of type III collagen in the dermis was only about 11% of normal. The child had the acrogeric form of EDS IV. He had the characteristic facies with a pinched nose, thin lips, and prominent eyes. These facial features, his aesthenic build, thin skin, prominent subcutaneous veins, and aged hands produced a 'cachectic' appearance. These features were evident in early childhood and worsened up to 12 1/2 years when he was last reviewed. Spontaneous bruising, bleeding from the large bowel, constipation, and delayed gastric emptying were other features. In cross section, the dermal collagen fibrils were round and measured 93.3 +/- 11.5 nm in diameter which was not significantly different from control values of 102.5 +/- 13.4 nm. The serum type III procollagen amino-terminal propeptide level of 25.5 ng/ml was within the normal age matched values of 15.5 +/- 7.7 ng/ml despite the low production of type III collagen by cultured fibroblasts. The child probably had a spontaneous new mutation in one COL3A1 allele as only normal sequences were obtained from the corresponding amplified region of the parent's leucocyte DNA. PMID- 1757961 TI - The midline craniofacial skeleton in holoprosencephalic fetuses. AB - Craniofacial skeletal development in eight human holoprosencephalic fetuses from second trimester abortions were examined by radiography and histology. The whole spectrum of associated facial malformations from anophthalmia through cyclopia, ethmocephaly, cebocephaly, and median cleft lip to short philtrum was represented. Cases with the most severe facial malformations also had the most severely affected facial skeleton. In the facial skeleton, the premaxilla was most often affected; it was absent in seven cases and malformed in the one with only a short philtrum. This and other facial skeletal malformations can be explained as abnormal fusion of the facial bones because of defective development of the nasal cartilage. The occipital bones were normal, but the basicranial skeleton anterior to the spheno-occipital junction was affected in all cases. The findings support the hypothesis that the facial malformations in holoprosencephaly result from disturbance in embryonal life of the mesoderm at the rostral end of the notochord. PMID- 1757962 TI - Determination of Duchenne muscular dystrophy carrier status by single strand conformation polymorphism analysis of deleted regions of the dystrophin locus. AB - The molecular characterisation of the dystrophin gene, mutations in which are responsible for X linked Duchenne and Becker muscular dystrophies, has led to an array of strategies for the diagnosis of affected subjects and carriers. Initially these were based on blotting and hybridisation technologies but have recently been largely superseded by PCR based techniques which afford greater speed and sensitivity. We describe the use of single strand conformation polymorphism to detect heterozygosity in regions of the dystrophin locus which are deleted in affected males, to determine the carrier status of their female relatives. PMID- 1757963 TI - Becker muscular dystrophy patient with a large intragenic dystrophin deletion: implications for functional minigenes and gene therapy. AB - The genetic defects responsible for the allelic disorders of BMD and the more severe DMD have been shown to be mutations within the dystrophin gene, which encodes a 14 kb transcript. We describe here a BMD patient who belongs to a small class of subjects with large in frame deletions of the dystrophin gene that remove apparently dispensable coding sequence, thereby producing functional truncated dystrophin. The in vitro reconstruction of these deletion derivatives of full length dystrophin transcripts should enable higher efficiency transfection of human muscle or murine germline cells using retroviral based vectors, compared with the full length transcript. This capability offers a means of examining retroviral mediated transfer as a potential therapeutic strategy in severely affected DMD patients. PMID- 1757964 TI - Arginine 109 to glutamine mutation in a girl with ornithine carbamoyl transferase deficiency. AB - We studied DNA from 29 families with at least one member with ornithine carbamoyl transferase (OCT) deficiency and have found a mutation in the TaqI site within exon 5 of the OCT gene in a female presenting at the age of 21 months. Hybridisation with site specific oligonucleotides shows that the mutation is a C to T substitution resulting in a glutamine for arginine substitution at amino acid 109. PMID- 1757965 TI - A cystic fibrosis patient who is homozygous for the G85E mutation has very mild disease. PMID- 1757966 TI - A cystic fibrosis patient with the nonsense mutation G542X and the splice site mutation 1717-1. AB - A cystic fibrosis patient with the genotype G542X/1717-1 (G----A) was identified by DNA sequencing of exon 11 of the CFTR gene. The available molecular and clinical data are presented. This is the first report of a patient with this rare genotype and may serve to improve our understanding of allele interactions. PMID- 1757967 TI - Multiple exostoses in a patient with t(8;11)(q24.11;p15.5). AB - The occurrence of multiple exostoses in a carrier of a balanced translocation t(8;11) (q24.11;p15.5) is described. The breakpoint on chromosome 8 is at proximal q24.1 within the critical region reported for Langer-Giedion syndrome. PMID- 1757968 TI - Phenotypic expression of the first liveborn 68,XX triploid newborn. PMID- 1757969 TI - Effects of an intrauterine copper device on serum copper, endometrial histology, and ovarian, hepatic, and renal functions in the Japanese monkey (Macaca fuscata fuscata). AB - A copper intrauterine device (Cu-IUD) was inserted transabdominally into the uterine cavity of eight Japanese monkeys (Macaca fuscata fuscata) for 4 to 6 months, and effects on various organ functions were examined. Results showed no significant effects on the menstrual cycle length, serum levels of LH, estradiol 17 beta, progesterone or clinical biochemical data such as serum copper, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, and blood urea nitrogen. Histology revealed edema and infiltration of eosinophilic leukocytes in the endometrium treated with a Cu-IUD. PMID- 1757970 TI - Auditory evoked potentials in the Japanese monkey. AB - Auditory sensitivity based on auditory brain stem response (ABR), whole nerve action potential (AP), and cochlear microphonics (CM) to tone bursts of 0.5-8 kHz were compared with behavioral audiometry in the Japanese monkeys. Although sensitivity loss at 4-6 kHz was observed in these potentials, an increase in sensitivity at 8 kHz was obtained only in the ABR. Thus the sensitivity loss at 4 6 kHz originates at the peripheral system and the increased sensitivity at 8 kHz originates at the central. PMID- 1757971 TI - Total serum creatine kinase and isozyme concentrations in the owl monkey. AB - Serum samples from 62 owl monkeys were analyzed to determine concentrations of creatine kinase activity and isozymes. Fifty monkeys were determined to be clinically normal, while twelve had cardiac disease. Findings showed that the data had a non-normal distribution. Based on nonparametric tests, significant differences were not observed between sexes or animals with and without cardiac disease, indicating that CK activity and isozymes are not reliable indicators of myocardial disease in the owl monkey. Reference values presented are only intended as a guide. Each laboratory should determine its own reference values. PMID- 1757972 TI - Altered lymphocyte phenotypes and proliferative responses in chimpanzees infected with hepatitis C virus. AB - Peripheral blood mononuclear cells (MNC) from three chimpanzees infected with hepatitis C virus (HCV) and from two uninfected animals were analyzed by monoclonal antibody phenotyping using flow cytometry. Significant differences in numbers of MNC's expressing cluster designation (CD) phenotypes CD4, CD14, CD19, and CD45RA were found. Additionally, significant differences in MNC proliferation in response to mitogens were also found. This altered proliferative capacity and cellular phenotype profile may be important markers in studying the pathogenesis of chronic HCV disease. PMID- 1757973 TI - Lymphocyte and neutrophil dysfunction associated with hepatitis B virus and hepatitis non-A, non-B virus infection in the chimpanzee. AB - Chimpanzees were examined for the effect of viral hepatitis infections on specific and nonspecific immune response mechanisms. The data suggest that infection with either hepatitis B virus or hepatitis non-A, non-B virus may result in suppression of cellular immune response components. Mitogen-induced lymphocyte proliferation was lower in virus-infected chimpanzees than in naive animals. Neutrophils from virus infected animals exhibited decreased or altered chemiluminescence kinetics. PMID- 1757974 TI - Induction of multiple follicular development and superovulation in the olive baboon, Papio anubis. AB - The objective of this study was to induce multiple follicular development and superovulation in the olive baboon. Beginning at menses, adult female baboons were treated with hMG for 10 days followed by hCG on day 11. Multiple follicular development was seen in all 19 animals; superovulation occurred in 11 of these. Serum E2 and P levels were consistent with multiple follicular and corpora lutea development, respectively. Ovulated ova were able to be fertilized. These results indicate that olive baboons can be superovulated using a regimen of hMG and hCG, however, development of antibodies against the human hormones precludes restimulation. PMID- 1757975 TI - Osmotic fragility of erythrocytes in Bolivian and Brazilian squirrel monkeys (Saimiri sciureus). AB - Median corpuscular fragility of erythrocytes does not differ significantly between fed and fasted Bolivian and Brazilian squirrel monkeys and are similar to values reported in humans and rhesus monkeys. This report further confirms that the fasting hyperbilirubinemia present only in Bolivian squirrel monkeys with a Gilbert-like syndrome is not due to an increased fragility of erythrocytes and should be classified as a nonhemolytic hyperbilirubinemia. PMID- 1757976 TI - Postnatal change in lipid composition and nerve conduction of peripheral nerves of young rhesus monkeys. AB - Body weight, motor and sensory nerve conduction velocities of fore and hind limbs, and lipid composition were measured sequentially in peripheral nerves of 15 rhesus monkeys. Initially measurements were made with monkeys six to eight months of age. There were significant increases in body weight, motor, and sensory nerve conduction and myelin marker lipids over a five months period, but no change was observed in free fatty acids, triglycerides, and esterified cholesterol. These results indicate that myelination continues at least for 11 to 13 months of postnatal age in rhesus monkeys. PMID- 1757977 TI - Exogenous progesterone recycling and early detection of pregnancy in rhesus monkeys. PMID- 1757978 TI - Sleep problems in children with mental handicap. AB - This paper reports on a longitudinal study of sleep problems in 200 children with severe mental handicap. Sleep problems were extremely common: 51% of children had settling problems, 67% of children had waking problems, and 32% of parents said they rarely got enough sleep. Sleep problems were also very persistent: between a half and two-thirds of children who exhibited sleep problems at Time 1 still had them 3 years later. Sleep problems were associated with a number of child characteristics: poor communication skills, poor academic skills, poor self-help skills, incontinence, daytime behaviour problems and epilepsy. There were no relationships with family variables such as social class, income, family composition or housing tenure. However, maternal stress, maternal irritability and perceived impact on the family were related to sleep problems. A Sleep Index was constructed, and path analysis was used to trace the main causal pathways of the child, family and social characteristics. Ten variables explained 50% of the variance in the Sleep Problems Index. Communication skills played a pivotal role. The implications of the findings for intervention strategies are discussed. PMID- 1757979 TI - Psychosocial effects on siblings of children with autism and mental retardation: a population-based study. AB - The probands of this study were 60 children and young adults between 5 and 20 years of age, 20 of whom had siblings with autism, 20 of whom had siblings with mental retardation, and 20 of whom had siblings who were free of handicap. The three proband groups were matched for gender, birth order and socioeconomic status. The children were questioned about their sibling relationships and about particular problems they faced concerning their handicapped brothers or sisters and about problems concerning themselves. Parents were interviewed about the healthy child's behaviour and social adjustment. Mothers completed the Eysenck Personality Inventory concerning themselves. Siblings of handicapped children and especially siblings of children with autism were more concerned about the future. They also felt lonely more often and many of them had peer problems. They often regarded their handicapped siblings as a burden. They tended to have only one sibling. Siblings often did not know why their handicapped brother or sister was different from other children. There were more behaviour disturbances in the siblings of handicapped children and mothers with a child with autism reported more 'stressful events'. There were no differences as regards the personality of the mothers and the self-concept of the children between the three groups. PMID- 1757980 TI - Clients' community and social contacts: results of a 5-year longitudinal study. AB - Clients' contacts with a range of community amenities and with their friends and relatives were examined to assess the impact of a new community-based service. Results over a 5-year period were compared for clients in different residential settings: supported ordinary housing, mental handicap hospital and private family homes. Findings indicated increased use of community amenities for those in supported housing and in their family homes. Little change was noted in clients' contact with relatives, and the paucity of social contact with friends was highlighted. Use of community amenities in relation to the development of social networks is discussed. PMID- 1757981 TI - The effect of social contact on college students' attitudes toward severely handicapped students and their educational integration. AB - Research on integration suggests that the major benefit of educational integrated programmes is the facilitation of intergroup contact between mentally handicapped and non-handicapped students. The present study was designed to investigate the effect of different amounts of social contact with severely handicapped students on attitudes and emotional reactions of college students towards such students and their integration into mainstream education. The study was carried out in a tertiary college which has a link programme with a local school for pupils with severe learning difficulties. The results indicated that those participants who had social contact with severely handicapped students held more favourable attitudes and emotional reactions toward such students than did those who had no social contact with this group. The study concludes that the educational integration programmes can positively modify attitudes and emotional reactions of college students towards severely handicapped students. However, in order to implement an effective link or integration programme and to foster attitudes more favourable towards severely handicapped students, the study recommends that more opportunities for intergroup contact and social interaction between non handicapped and handicapped students need to be provided. PMID- 1757982 TI - The sterilization of people with a mental handicap: the views of parents. AB - The issue of sterilization in people with mental handicap has re-emerged in recent years. Historical aspects are briefly reviewed, and attention is drawn to the different context in which this issue has been revived. A postal survey of parental views was undertaken. Fifty-three per cent of the respondents indicated that they had or would consider sterilization for their child with mental handicap, and a large majority of the parents felt that they alone, or in conjunction with a doctor, should be able to consent on behalf of the person with mental handicap. Consideration needs to be given to parental anxieties with regard to sexual and reproductive health issues which are surfacing with the current emphasis on community care and the philosophy of normalization. PMID- 1757983 TI - Musical aptitudes, musical interests and mental retardation. AB - A modified version of the Bentley scales of musical aptitude was given to a sample of mild and moderately retarded adults chosen on the basis of alleged musical interest or experience. Several comparison groups were also given the assessment battery. The musical nominees generally performed more accurately than both matched retarded subjects with no particular musical interests and a group of normal children matched on (Wechsler) vocabulary scores. The musical nominees showed especially high performance on the subtest assessing voice analysis in chords. PMID- 1757984 TI - Paradox, reprimand and extinction in adults with mental handicap. AB - To assess the efficacy of paradoxical directives, levels of challenging behaviour during 2 weeks of paradox, reprimand and extinction were compared with baseline levels in four adults with mental handicaps attending a day centre. Paradox was the most effective procedure for reducing the frequency and severity of challenging behaviour by an average of over 70% by the end of 2 weeks and up to 90% in certain subjects; extinction was least effective. Paradox was most effective with more defiant subjects, when staff rated treatment success as low, when improvement using extinction and reprimand was poorest, and in reducing aggressive behaviour. The present authors suggest the overjustification effect offers an explanation for the effects of paradox. PMID- 1757985 TI - Kensington & Chelsea and Westminster Planning Register for People with Severe Learning Difficulties. PMID- 1757986 TI - A strategy for the reconstruction of structures possessing axial symmetry: sectioned axonemes in sperm flagella. AB - The images of complex biological structures seen in the electron microscope, possessing an n-fold rotational symmetry, can be enhanced by averaging the axially repeating motif in order to improve their signal-to-noise ratio; this requires that the slices with n-fold symmetry do not exhibit distortions relative to one another. A strategy is proposed to detect the relative distortions and to remove them in order to obtain reliable results from the averaging process. Extensive use is made of cross-correlation analysis and of interpolation; because the procedure involves iterated resampling of the image, it is essential to adopt interpolation algorithms which preserve the spectral power. The procedure is illustrated by the analysis of transverse sections of the sperm flagellum axoneme of a stick insect; it might be used for the reconstruction of microtubules, nuclear pore complexes, virus capsids, and other supramolecular aggregates. The reconstructed images of axoneme sections reveal new information about the interactions between adjacent doublets; in particular, a double conjunction connecting the inner dynein arm with the nearest B-tubule has been consistently observed. PMID- 1757987 TI - Axial resolution of confocal microscopes with parallel-beam detection. AB - We present a simple theory for the evaluation of the axial resolution of a confocal scanning microscope with parallel-beam detection. The results demonstrate that, in certain cases, the collection efficiency is low compared with a conventional confocal microscope, but the axial resolution may be further improved. PMID- 1757988 TI - A note on stereological estimation of the volume-weighted second moment of particle volume. AB - It is shown that for a variety of biological particle shapes, the volume-weighted second moment of particle volume can be estimated stereologically using only the areas of particle transects, which can be estimated manually by point-counting. PMID- 1757989 TI - A preparation method of specimens of the fungus Penicillium chrysogenum for ultrastructural and immuno-electron microscopical studies. AB - A combination of cryofixation without pre-treatment, freeze-substitution and low temperature embedding was used to prepare specimens of Penicillium chrysogenum for electron microscopy. To produce specimens which are thin enough for appropriate cryofixation, the P.chrysogenum colonies were grown between dissected dialysis tubing on an agar plate, which in addition allowed longitudinal sectioning. In contrast to classical chemical fixation, this preparation procedure resulted in excellent preservation of ultrastructure. Furthermore, the penicillin biosynthetic enzyme acyltransferase could be unequivocally located by immunogold labelling, indicating a preservation of antigenic properties of the specimen. Labelling density was not conspicuously affected when using different freeze-substitution media, but it was reduced after embedding in Epon 812. PMID- 1757990 TI - Application of scanning electron microscopy (SEM) and microbead techniques to study the localization of p24 and p18 antigens of HIV-1 on the surface of HIV-1 infected H9-lymphocytes. AB - Immunofluorescence staining techniques at present, when applied to follow the expression of HIV-1-specific antigens on infected cells, only give the information that the antigens detected are localized in the outer region of the membrane of the infected cell. We therefore set up a procedure using magnetic polystyrol particles coated with antibodies specific for the HIV-1 antigens under study, in combination with scanning electron microscopy. We were able to demonstrate that p24 and p18 structural antigens are clearly expressed on the surface of HIV-1-infected H9 lymphocytes. This means that there was no steric hindrance for structures of cell-like size specific for HIV-1 antigens to interact with their target antigens. Other antigens may be hidden in membrane structures and are therefore inaccessible, for example, to the beads used here, which were of a similar size to antigen-specific cells in vivo. The results of this model system must be seen with respect to the interaction of antigen specific cell-mediated immunity with full antibody-dependent cellular cytotoxicity, or without cytotoxic T lymphocytes, the mediator function of antibodies. PMID- 1757991 TI - Suggestions for the quantitative X-ray microanalysis of thin sections of frozen dried and embedded biological tissues. AB - When a microregion in a thin section of frozen-dried and embedded tissue is analysed by the conventional electron-probe X-ray continuum-normalization method, the measured quantity is in mmol of element per kg of embedded specimen. As each microregion contains an unknown amount of embedding medium, this quantity generally lies indeterminately somewhere within the wide range between mmol of element per kg of hydrated tissue and mmol of element per kg of dehydrated tissue. However, if a 'tag' element is incorporated in the embedding medium, the contribution of the medium to the local continuum count in each probed field should be measureable, and the X-ray data may then unambiguously yield mmol of element per kg of dehydrated tissue. This result should not be affected by shrinkage on freeze-drying or by incomplete replacement of water by embedding medium. The same X-ray data can additionally provide estimates of mmol of element per unit volume, mmol of element per kg of hydrated tissue and local dry-mass fraction. However, these estimates are subject to errors due to tissue shrinkage, incomplete replacement of water and beam damage. PMID- 1757992 TI - Different rates of substitution may produce different phylogenies of the eutherian mammals. AB - In an attempt to resolve some points of branching order in the phylogeny of the eutherian mammals, a phylogenetic analysis of 26 nuclear and 6 mitochondrial genes was undertaken using a maximum likelihood method on a constant rate stochastic model of molecular evolution. Seventeen of the nuclear genes gave a primates/artiodactyls grouping highest support whereas three of the mitochondrial genes found a rodents/artiodactyls grouping to be best supported. The primates/rodents grouping was never the best supported. On the assumption that rodents are indeed an outgroup to primates and artiodactyls and that the latter taxa diverged 70 million years ago, an estimation was made, for each gene, of the time of divergence of the rodent lineage. In most cases such estimates were beyond the limits set by present interpretations of the paleontological record as were many estimates of the divergence time of mouse and rat. These results suggest that, although there is locus variation, the divergent position of the rodent lineage may be an artifact of an elevated rate of nucleotide substitution in this order. PMID- 1757993 TI - Genes encoding the small subunit of RUBISCO belong to two highly conserved subfamilies in Nicotianeae. AB - The sequences of seven complementary DNAs or genes encoding the small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase oxygenase (RUBISCO) in several Nicotianeae were examined. Two new SSU genes isolated from Nicotiana sylvestris were included. Both sequence comparisons and Southern analyses with specific probes reveal that SSU genes fall into two homogeneous subfamilies that are highly conserved in Nicotianeae and are also present in other Solanaceae. Additional criteria such as number of introns and level of expression fitted to this classification. Homogeneity must have been maintained by gene conversion and/or an unusually high fidelity of DNA replication, whereas traces of slippage stranded DNA mispairing and/or transposition probably explain local changes. Taken as a whole, these results show that the divergence between the two subfamilies predated the divergence between genera inside the Solanaceae, but that Nicotianeae retained the most simple SSU gene family structure. PMID- 1757994 TI - Nonrandom CpG mutations affect the synonymous codon usage of moderately GC-rich single copy actin genes. AB - In species where actin genes exist as single copies, analysis of their synonymous codon usage and of the substitutions occurring between the genes of closely related species shows that there is a positive selection for codons that do not have highly mutable CpG dinucleotides in codon positions 2 and 3 when the GC content of these genes is less than 57%. PMID- 1757996 TI - Distinct patterns in the dinucleotide nearest neighbors to G/C and A/T oligomers in eukaryotic sequences. AB - The eukaryotic and prokaryotic databases are scanned for potential nearest neighbor doublet preferences at the 5' and 3' flanks of some oligomers. Here we focus on oligomers containing alternating nucleotides, i.e., UV, UVUV, and UUVV where U not equal to V. Strong, consistent trends are observed in eukaryotic sequences. A/T alternation oligomers are preferentially flanked by A/T. G/C flanks are disfavored. G/C alternation oligomers are preferentially flanked by G/C. A/T flanks are disfavored. These trends are consistent with those observed previously for homooligomer tracts (Nussinov et al. 1989a,b). G/C tracts are preferentially flanked by G/C. A/T nearest neighbors are disfavored. The reverse holds for A/T tracts. Additional patterns are described here as well. The possible origin of these DNA composition and sequence trends is discussed. These trends are suggested to stem from protein-DNA interaction constraints. PMID- 1757995 TI - Molecular considerations in the evolution of bacterial genes. AB - Synonymous and nonsynonymous substitution rates at the loci encoding glyceraldehyde-3-phosphate dehydrogenase (gap) and outer membrane protein 3A (ompA) were examined in 12 species of enteric bacteria. By examining homologous sequences in species of varying degrees of relatedness and of known phylogenetic relationships, we analyzed the patterns of synonymous and nonsynonymous substitutions within and among these genes. Although both loci accumulate synonymous substitutions at reduced rates due to codon usage bias, portions of the gap and ompA reading frames show significant deviation in synonymous substitution rates not attributable to local codon bias. A paucity of synonymous substitutions in portions of the ompA gene may reflect selection for a novel mRNA secondary structure. In addition, these studies allow comparisons of homologous protein-coding sequences (gap) in plants, animals, and bacteria, revealing differences in evolutionary constraints on this glycolytic enzyme in these lineages. PMID- 1757997 TI - Molecular evidence for the origin of plastids from a cyanobacterium-like ancestor. AB - The origin of plastids by either a single or multiple endosymbiotic event(s) and the nature of the progenitor(s) of plastids have been the subjects of much controversy. The sequence of the small subunit rRNA (Ssu rRNA) from the plastid of the chlorophyll c-containing alga Cryptomonas phi is presented, allowing for the first time a comparison of this molecule from all of the major land plant and algal lineages. Using a distance matrix method, the phylogenetic relationships among representatives of these lineages have been inferred and the results indicate a common origin of plastids from a cyanobacterium-like ancestor. Within the plastid line of descent, there is a deep dichotomy between the chlorophyte/land plant lineage and the rhodophyte/chromophyte lineage, with the cyanelle of Cyanophora paradoxa forming the deepest branch in the latter group. Interestingly, Euglena gracilis and its colorless relative Astasia longa are more related to the chromophytes than to the chlorophytes, raising once again the question of the origin of the euglenoid plastids. PMID- 1757998 TI - A comparison of 18s ribosomal RNA and rubisco large subunit sequences for studying angiosperm phylogeny. AB - Partial sequences of 18s rRNA were obtained for 2 gymnosperms and 12 angiosperms from a wide range of families and these were analyzed with 5 other published sequences to form a phylogenetic tree. Using 16 published sequences of the large subunit of rubisco (rbcL), also from a wide range of angiosperm families, another phylogenetic tree was derived and the two approaches were compared. Both phylogenetic trees gave good grouping within families but in neither case was there resolution of the branching order of major taxa. Superficially the long rbcL sequences (whose base composition was homogeneous among all species) seemed very promising, but analysis showed that a large proportion of the variation did not affect the amino acid sequence. Although silent substitution contained some phylogenetic information, at the level required to order major taxa, much of it was random and obfuscating. It was concluded that neither macromolecule alone was likely to yield a solution to the problem of angiosperm phylogeny and therefore that studies of both, at least, will be required. For this reason, a method was described for obtaining both DNA and RNA of good quality from the same preparation and which had been used successfully with a wide range of species including many with pungent leaves. PMID- 1757999 TI - Evolution of a family of N-acetylglucosamine binding proteins containing the disulfide-rich domain of wheat germ agglutinin. AB - A disulfide-rich domain, first identified in wheat germ agglutinin, has now been identified in the amino acid and DNA sequences of a large number of other chitin binding proteins. This 43-residue domain includes eight disulfide-linked cysteines and has been implicated in the binding of N-acetylglucosamine and its polymers. This study used 12 complementary DNA sequences and 1 amino acid sequence of proteins with one, two, and four copies of this domain to infer a 44 amino acid residue ancestor sequence for this domain, and to derive an evolutionary tree relating these domains in the different proteins. The tree relating these single-domain sequences is divided into two major branches, one consisting of the multidomain dimeric lectins, which we have earlier suggested arose by duplication of a single copy of the disulfide-rich domain, and the other branch consisting of the monomeric chitinases and wound-inducible proteins, which have a single copy of the domain fused to a larger polypeptide. Reference to the three-dimensional structure of WGA and its saccharide complexes shows that the saccharide-binding residues as well as cysteine and glycine residues are conserved among all available sequences. In contrast, many residues at the dimer interface of the domains of WGA are not conserved in those proteins with a single domain, implying that the aggregation state of the domains in these proteins differs from that of the gras lectins. Also, the base compositions of the four domain and one-domain branches of the tree differ, indicating distinct selective pressures at the level of both protein structure and the gene or its transcript. PMID- 1758000 TI - Reclaiming sexuality in female incest survivors. AB - This paper presents a comparison of female incest survivor sex therapy patients and other sex therapy patients. The focus is on family-of-origin dynamics and processes of teaching about sexuality, self-image and resulting interpersonal issues. The study also discusses nonincest survivor and incest survivor sex therapy clients with low sexual desire, their evaluation and treatment. PMID- 1758001 TI - The role of assertiveness in female sexuality: a comparative study between sexually assertive and sexually nonassertive women. AB - To examine the role of assertiveness in female sexuality, a nonclinical population of married women (ages 18-31 years) were stratified as above or below the median score (73) on sexual assertiveness, as measured by the Hurlbert Index of Sexual Assertiveness (HISA), and matched accordingly for demographics, resulting in two samples: sexually assertive and sexually nonassertive, each group consisting of 50 women. Comparative assessments were made between the two matched samples on frequency of sexual activity, number of orgasms, subjective sexual desire, and both marital and sexual satisfaction. The t-test was used to test the equality of means between samples. Pearson's r was used for correlational data. ANOVA methods were employed to examine race, religion, and employment status. Using t-test, significant differences between the two groups appeared on all five measures. Sexually assertive women reported higher frequencies of sexual activity and orgasms, rated themselves as having greater subjective sexual desire, and reported greater marital and sexual satisfaction. PMID- 1758002 TI - Assessment of erectile dysfunction in diabetic men: the clinical relevance of self-reported sexual functioning. AB - Diabetes mellitus is commonly associated with erectile dysfunction (ED). Fifty three diabetic male veterans presenting with ED underwent an extensive medical examination, psychological evaluation, and a detailed assessment of sexual functioning. They then underwent two consecutive nights of inhospital Rigiscan monitoring to assess erectile capacity. Multivariate analyses indicated that patient reports of a.m. erections and erectile quality were highly predictive of Rigiscan measures of penile tip and base rigidity and duration of erectile episodes. These results highlight the importance of attending to patient reports of specific sexual symptomatology in the evaluation of diabetic patients presenting with ED. PMID- 1758003 TI - Western and non-western human sexuality: implications for clinical practice. AB - The emergence of the "new sex therapies" in the early 1970s has brought more people, from more diverse cultural groups, to seek help for sexual problems. However, the directive approach in sex therapy seems be deemphasize cultural differences by offering a set of procedures and techniques that clearly are grounded in Western sexual values. Based on existing literature concerning cultural values and clinical observations, the idea that the commonly practiced sex therapy is useful for everybody is challenged. Four culturally determined factors are discussed: 1) the meaning of sexuality; 2) the definition of normal sexual relationship; 3) the perception and meaning of sexual dysfunctions; and 4) the role of the therapist and therapist-client relations. Finally, implications for practice are presented. PMID- 1758004 TI - Enriching the sexual experience of couples: the Asian traditions and sexual counseling. AB - Drawing from Hindu and Buddhist Tantric traditions, central themes reflecting Asian approaches to sexuality are described and contrasted with contemporary values, assumptions, and objectives implicit in both sexual experience and in the clinical practice of sexual counseling. The Tantric ceremonial sex ritual provides a fertile source for several innovative behavioral assignments useful in sexual counseling. Five exercises in intimacy derived from the ancient Tantric sex ritual are presented and suggested as home assignments for couples: the creation of a ritual, synchronized breathing, sustained eye contact, motionless intercourse, and sexual exchange without orgasm. Applications to intimacy development, sexual enhancement, and sexual counseling for couples are described, creating a broad and meaningful context for responding to clients' sexual concerns. PMID- 1758005 TI - Multiple severe sexual dysfunctions resolved in brief sex therapy. AB - The following case illustrates the use of integrative sex therapy techniques in treating a couple with numerous sexual dysfunctions. The integrative method enables the therapist to address sexual difficulties in both partners simultaneously and significantly reduce the time of treatment. PMID- 1758006 TI - Late seroconversion to hepatitis B in a Somali village indicates the important role of venereal transmission. AB - Hepatitis B virus (HBV) markers were investigated in a cross-sectional study in 1985 on sera from 84% of the 648 inhabitants in a rural Somali village. The prevalence of HBV markers increased with age, from 9.7% in subjects less than 12 years old, to 38% in the age group 12-19 years, and to 68% in adults. HBV markers were more common in boys less than 12 years old, 13%, than in girls of the same age group, 5.8% (P less than 0.05). A rapid increase of HBV markers started at adolescence in both sexes. The female cohort showed their highest seroconversion rate during their second decade of life, while the male cohort seroconverted more rapidly in the third decade. Thus, an initially more rapid seroconversion among boys was reversed when the females reached reproductive age, and no sex difference in marker frequencies was observed in the age group 12-19 years. There was a steady increase of HBV markers during the reproductive years in both sexes. The frequencies of HBsAg, as well as total markers, were significantly higher in adult males than females, 14 vs 5.6%, and 77 vs 62%, respectively. HBV markers were more frequent in wives of HBV positive husbands than in those married to HBV negative husbands. No increased marker prevalence was observed among siblings of HBV positive children, nor among their mothers, which disproved the role of vertical and early horizontal transmission. In 1989 the four-year rate of seroconversion was investigated in villagers who were seronegative in 1985. On testing 158 sera from 319 individuals, the seroconversion rate was significantly lower among those younger than 12 years in 1985 compared to those in the older age group, 5 vs 17%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758007 TI - Paradoxical response to chemotherapy for intracranial tuberculoma: two case reports from Saudi Arabia. AB - Two patients with tuberculous meningitis are described, who developed intracranial tuberculoma while receiving antituberculous therapy. The tuberculoma responded to the same regimen of treatment and small dose of corticosteroids. Such paradoxical reaction should be looked for if the patient develops new neurological signs during the course of the disease. PMID- 1758008 TI - Beliefs about the prevention of dengue and other febrile illnesses in Merida, Mexico. AB - A series of open interviews and a survey were conducted in several neighbourhoods in the city of Merida, Mexico to find out whether poor response to government dengue control programmes might be related to the explanatory models about dengue and its prevention held by community members. Dengue was grouped by informants with other mild febrile illnesses, all of which were thought to be inevitable and capable of converting into more serious illnesses. Although vector control personnel think of prevention in terms of eliminating the larval habitats of mosquito vectors, the form of prevention most commonly described involved looking after oneself once sick, so that mild fevers do not evolve into serious fevers. Due to the prevalence of this different model of prevention, it is argued that simple messages about dengue may be misinterpreted. Vector control programmes need to take into account local models of febrile illnesses and their prevention in order to be effective. PMID- 1758009 TI - Potential sources of Campylobacter species in the homes of farmworkers in Zimbabwe. AB - Chicken faeces, houseflies, household stored drinking water, cooked or prepared foods and handwashings of people of all age groups and hands of children under 5 years old were examined as potential sources and transmission routes of Campylobacter species in a farmworker community. Campylobacter species were found to be common in chicken faeces collected from the homesteads of the farmworkers but were rarely isolated from houseflies or household stored drinking water. They were not isolated from foods and hands of people of all ages. A comparison of Campylobacter species isolated from humans and chickens showed Campylobacter jejuni to be more common than Campylobacter coli in human isolates while the two species were evenly distributed in chickens. Most of the C. jejuni isolates from humans and chickens belonged to biotype II and none belonged to biotype III. There was some similarity in some C. jejuni serotypes isolated from humans and chickens. Chickens were therefore found to be the main potential source of Campylobacter species in the homes of farmworkers. PMID- 1758010 TI - Cryptogenic chorea. AB - A total of 40 cases of cryptogenic chorea were studied over a period of 4 years in JIPMER Hospital which serves the population of Pondicherry and adjoining regions of South India. Analysis of our cases showed the highest incidence for the 10-15 year age group with no sex predilection. Arthralgia and non-specific fever preceded the onset of chorea in most patients. The majority had generalized chorea of variable severity. Laboratory evidence of rheumatic fever was absent in all cases. The socioeconomic, environmental and cultural factors contributing to persistently high rate of infections together with the absence of evidence of a rheumatic process indicate a non-rheumatic aetiology. PMID- 1758011 TI - The occurrence and driver characteristics associated with motor vehicle injuries in Addis Ababa, Ethiopia. AB - Ethiopian documentation of the occurrence and determinants of motor vehicle related morbidity and mortality is sparse. The purpose of this investigation was to determine the incidence of hospital treated motor vehicle injuries (MVI) in Addis Ababa and driver characteristics associated with involvement in a MVI. The study was conducted over a 12-week period in the autumn of 1988. Over 91% of MVI involved pedestrians. The overall MVI incidence density rate was 279.4 per 100,000 person years and the mortality rate was 17.6 per 100,000 population per year. Road accident injury and fatality rates were 946 and 59.5 respectively per 10,000 registered vehicles. Overall years of person life lost was 595 per 100,000 person-years exposure. Significantly increased odds of exposure among drivers inflicting a MVI were found for younger age, fewer years driving experience, male gender, and those driving newer, government owned, and mass transit vehicles. PMID- 1758012 TI - The usefulness of urinalysis reagent strips in selecting Schistosoma haematobium egg positives before and after treatment with praziquantel. AB - The effectiveness of urinalysis reagent strips for haematuria and proteinuria in selecting Schistosoma haematobium egg-positive persons was studied on 426 subjects of all ages in a Kenyan community before and 3 months after treatment with praziquantel. Before and after treatment, the degree of urinary blood or protein and prevalence of egg positives were closely associated. Haematuria and proteinuria were positively correlated with urinary egg counts. For selecting egg positive persons with reagent strips, a combined criterion 'haematuria trace up or proteinuria 1 + up' was considered the best in this area. With this criterion, sensitivity and specificity before treatment were 69.6 and 84.4 respectively. These values remained at the same level (70.7 and 81.2%) even after treatment with praziquantel reduced prevalence from 59.4 to 13.6% (77% reduction) and intensity of infection from 57.2 to 11.3 eggs 10 ml-1 of urine (80% reduction). Although the sensitivity was not very high, heavy infections were not missed. If all those selected with reagent strips were treated and cured, a 98% reduction in total egg excretion by the community would be expected in both our first and second urine examinations. PMID- 1758013 TI - Antimicrobial resistance trends of shigellae isolates from Calabar, Nigeria. AB - During a 3-year study (January 1986-December 1988), stools of 2200 diarrhoeal or dysenteric patients were examined by culturing and 108 (4.9%) were found positive for shigellae. Shigella flexneri was the commonest species isolated (54.6%), followed by Sh. dysenteriae (24.1%). Patients aged less than or equal to 15 years accounted for 51.4% of cases. Shigellae over the 3 years showed high and sometimes rising resistance to ampicillin, chloramphenicol, streptomycin and cotrimoxazole and complete resistance to tetracyclines and sulphonamides. Sh. sonnei strains isolated in 1986 and 1987 were almost invariably sensitive to all antimicrobial agents except ampicillin, while in 1988 strains were resistant to all. The isolation rate was higher (74.1%) during the dry season than in the rainy season (25.9%) (P less than 0.01). Low standards of community and personal hygiene and improper sewage disposal are the prevailing epidemiological factors identified. PMID- 1758014 TI - Gastrointestinal parasitic infection in healthy Jamaican carriers of HTLV-I. AB - A subsample (1.6%; n = 13,260) of a healthy Jamaican population of food-handlers, studied by Murphy et al. (1991), who were serologically positive (n = 99) or negative (n = 113) for HTLV-I was investigated for intestinal parasitic infection using coprological methods. Helminth infection included Ascaris lumbricoides (2.8%), Trichuris trichiura (7.1%) and hookworms (6.1%). Entamoeba coli was found in 21.8% of samples, while E. hartmanni, Giardia lamblia, Endolimax nana, Iodamoeba butschlii and Chilomastix mesnili each occurred in less than 10% of responders. T. trichiura displayed a higher prevalence (10.6 vs 3%) (chi 2 = 4.623; P = 0.03) in the HTLV-I negative group. G. lamblia was detected more frequently among HTLV-I carriers compared to controls (9.1 and 3.5%, respectively), but the association was not statistically significant (chi 2 = 2.825; P = 0.09). Infection with intestinal parasites is likely to occur independent of HTLV-I status: however, possible HTLV-I-induced immunosuppression may lead to higher intensity infections of certain organisms thus facilitating easier detection using parasitological methods. The immunomodulatory potential of HTLV-I infection in the aetiology of non-malignant diseases requires further investigation. PMID- 1758015 TI - The epidemiology of human brucellosis in a well defined urban population in Saudi Arabia. AB - A retrospective survey was undertaken to provide the first reported estimate of the incidence of human brucellosis in Saudi Arabia. The study population was unusually well defined and consisted of all individuals resident in the Riyadh and Al Kharj regions and registered for treatment in the Riyadh-Al Kharj Hospital Program. Cases satisfying predetermined case criteria were identified initially from a retrospective review of hospital laboratory records, and this was supported by a review of individual medical case-notes. Brucellosis was found to be much more common in Saudi nationals than expatriate nationals. Among Saudi nationals the study demonstrated a remarkable increase in brucellosis with increasing age, and a higher incidence amongst women than men in some age groups. This was felt to have been due either to an increased exposure to infected livestock, or to an increased susceptibility to the disease in women, and with increasing age. There was a seasonal fluctuation in the occurrence of brucellosis with the largest number of cases occurring in spring and summer. PMID- 1758016 TI - Human hydatidosis in Niger. AB - Thirty-two cases of hydatidosis were collected in two Nigerian hospitals during a 5-year period; 81% of these had extra-hepatic localizations. Human hydatidosis has been considered as exceptional in West Africa but seems to be an underestimated disease in Niger. Studies in slaughtered animals from Niger show a high prevalence of hydatidosis in camels while no infection was found among sheep. PMID- 1758017 TI - Yersiniosis in free-ranging muskoxen on Banks Island, Northwest Territories, Canada. AB - Sixty-seven muskox (Ovibos moschatus) carcasses, 53 skeletal remains and two sick muskoxen were seen during an aerial survey of the Thomsen River region, northern Banks Island, Northwest Territories, Canada in late July 1986. Complete necropsies were performed on 29 muskoxen estimated to have died within the previous 3 to 5 days. Twenty were diagnosed with acute yersiniosis due to Yersinia pseudotuberculosis serotype 1B and were in excellent body condition. A diagnosis could not be made on seven animals due to marked autolysis; however, these muskoxen also were in excellent body condition. The remaining two were aged, emaciated muskoxen. This report describes the first occurrence of yersiniosis in free-ranging muskoxen and the first documentation of large scale mortality due to this disease in a free-ranging population of wild ungulates. PMID- 1758018 TI - Spontaneous pasteurellosis in captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis): clinical, laboratory, and epizootiological observations. AB - We observed clinical signs, compared adrenal responses, and performed diagnostic tests on 12 captive Rocky Mountain bighorn sheep (Ovis canadensis canadensis) during a spontaneous outbreak of pasteurellosis. Cortisol in urine and feces was measured for bighorns sampled three times between 20 October and 1 November 1986. By 6 November, four of these had developed pneumonia, four showed only mild rhinitis, and four remained clinically normal. Bighorns that ultimately developed pneumonia showed elevated mean urinary (P = 0.003) and fecal (P = 0.046) cortisol excretion over the 12-day sampling period. Twenty-four hour mean urine cortisol: creatinine ratios ranged from 10 to 57 ng/mg dry matter for affected and 5 to 22 ng/mg for healthy individuals; 24 hr mean fecal cortisol concentrations ranged from 7.2 to 20 ng/g dry matter for affected and 3.6 to 9.1 ng/g dry matter for healthy individuals. Elevated cortisol excretion preceded clinical pneumonia in affected bighorns by less than or equal to 16 days. Beta-hemolytic Pasteurella haemolytica biotype T, serotype 3 or 4, was isolated from nasal and pharyngeal swabs from all eight bighorns with pneumonia or mild rhinitis. We detected no evidence of parainfluenza 3, bovine respiratory syncytial virus, or Chlamydia psittaci using fluorescent antibody and/or serologic tests. Although elevated cortisol excretion was associated with pneumonia, we also believe age, reproductive physiology, and/or prior recovery from clinical pasteurellosis may have influenced individual susceptibility to pneumonia during this epizootic. PMID- 1758019 TI - Correlations of daily activity with avian cholera mortality among wildfowl. AB - We tested the hypothesis that wildfowl activities can influence the risk of avian cholera (Pasteurella multocida infection) for susceptible birds at Centerville, Humboldt County, California (USA). Avian cholera mortality characteristics from past epizootics were correlated with variations in flock size, habitat use and 11 feeding and nonfeeding behaviors among six empirically defined groups of wildfowl: American coots (Fulica americana), tundra swans (Cygnus columbianus), American wigeon (Anas americana), northern pintails (A. acuta), northern shovelers (A. clypeata)/mallards (A. platyrhynchos), and teal (A. discors, A. crecca, A. cyanoptera). The position of these wildfowl groups in past mortality sequences was directly correlated with mean flock size, time spent on land, and time spent grazing on land or in shallow water. We propose that variations in bird density, habitat use and frequency of grazing may serve as predisposing factors to avian cholera among wildfowl. PMID- 1758020 TI - Salmonellosis in laboratory-housed iguanid lizards (Sceloporus spp.). AB - Fifteen wild-caught iguanid lizards (14 Sceloporus variabilis and one S. malachiticus) were used in a 3 mo study on thermal acclimation. Over a 2 mo period, five of the lizards showed decreased activity, anorexia and enlarged joints, and were either found moribund or were euthanatized due to their poor condition. Specimens taken from lesions in four of the five lizards were cultured and were infected with Salmonella spp. Salmonella spp. was cultured from cloacal swabs in six of the 10 surviving lizards. Standard metabolic rates of those that were infected did not differ significantly from those that were not infected. We postulate that the lizards were inapparent carriers of Salmonella spp. at the time of capture and, as a result of stress, five developed active overwhelming systemic infections. PMID- 1758021 TI - S-layer positive motile aeromonads isolated from channel catfish. AB - Motile aeromonads are ubiquitous aquatic bacteria that can cause motile aeromonad septicemia (MAS), a disease which affects channel catfish and can produce significant economic loss. Motile aeromonads isolated from commercially-raised channel catfish were screened for production of S-layer protein in order to evaluate its potential role in natural epizootics. The S-layer protein was produced by 14 of 24 (58%) isolates from epizootics evaluated in this study. Concomitant infections with other internal pathogens were detected in 10 of the 24 cases used in this study, and only one of those 10 isolates (10%) produced the S-layer protein. When Aeromonas sp. was the only internal pathogen diagnosed, 13 of 14 (93%) isolates produced the S-layer protein. PMID- 1758022 TI - Antibodies to Borrelia burgdorferi in deer and raccoons. AB - An enzyme-linked immunosorbent assay (ELISA) was developed to detect serum antibodies to Borrelia burgdorferi, the causative agent of Lyme borreliosis, in deer (Odocoileus virginianus) and raccoons (Procyon lotor). Blood samples were collected from these mammals in Connecticut, Maryland, North Carolina, Georgia and Florida. Seropositivity for deer was highest in Connecticut (56% of 353 sera) and Maryland (51% of 35 sera). Raccoons in Connecticut, Maryland, North Carolina, and Florida also had antibodies to B. burgdorferi, but prevalence of positive sera was highest in Maryland (79% of 14 samples). Based on adsorption tests, the immunoglobulins detected in these mammals were probably specific to B. burgdorferi. The ELISA was more sensitive than an indirect fluorescent antibody staining method and was more suitable for analyzing large numbers of serum samples. PMID- 1758023 TI - Influence of habitat modification on the community of gastrointestinal helminths of cotton rats. AB - Dynamics of communities of gastrointestinal helminths of cotton rats (Sigmodon hispidus) were monitored in response to five experimental brush management treatments using herbicide applications with and without prescribed burning on the Cross Timbers Experimental Range in Payne County, Oklahoma (USA). A total of 113 adult cotton rats (68 male and 45 female) was collected from experimental pastures in winter and summer 1986 resulting in the recovery of five species of helminths: Longistriata adunca, Syphacia sigmodontis, Strongyloides sp., Protospirura muris, and Raillietina sp. Prevalences of Raillietina sp. and S. sigmodontis were greater on control than herbicide-treated pastures. Prevalence and abundance of Raillietina sp. and prevalence of S. sigmodontis were significantly lower on annually burned, herbicide-treated pastures compared to unburned herbicide-treated pastures. Triclopyr-treated pastures had greater abundances of L. adunca and lower abundances of Raillietina sp. than those treated with tebuthiuron. Abundances of L. adunca also decreased from winter to summer on annually burned, herbicide-treated pastures while increasing on other pastures. Distribution of all helminths was overdispersed, but distribution of L. adunca showed a significant brush treatment by season interaction as a result of greater overdispersion in summer than winter for cotton rats inhabiting brush treated pastures. Our results indicate that man-induced habitat modifications can alter host-parasite relationships in the community. PMID- 1758024 TI - Prevalence of Parelaphostrongylus tenuis in white-tailed deer in northern New York. AB - The prevalence and distribution of "brainworm" (Parelaphostrongylus tenuis) were examined in northern New York (USA) from 1986 to 1989. Sixty nine (46%) of 151 white-tailed deer (Odocoileus virginianus) heads examined, contained adult P. tenuis. The proportion of infected individuals was not significantly different between males and females. Prevalence was significantly greater in the adult age class as compared to the juvenile age class (P less than 0.01). Deer pellet samples were examined for prevalence of P. tenuis-like larvae. Pellet samples in New York had an overall prevalence of 60%. The effects of precipitation and host density on prevalence of P. tenuis in deer was not significant. PMID- 1758025 TI - Efficacy of triclabendazole against natural infections of Fascioloides magna in wapiti. AB - Fourteen free-ranging adult wapiti (Cervus elaphus nelsoni) were captured in Banff National Park, Alberta (Canada) and held in captivity near Edmonton. A 24% suspension of triclabendazole at doses of 30 to 100 mg/kg body weight was drenched into the rumen of eight females and four males. Two male wapiti were used as untreated controls. Animals were killed and examined at 4 (n = 3), 6 (n = 4), or 8 (n = 4) wk after treatment. Efficacy was 90% against immature Fascioloides magna collected 4 wk after treatment and 98% against adult flukes collected 4, 6 or 8 wk after treatment. All 32 flukes recovered from control wapiti were active and apparently healthy. Treatment at 50 to 60 mg/kg is recommended against F. magna in wapiti. A protocol for treating infected wapiti is outlined. PMID- 1758026 TI - Tick infestations of white-tailed deer in Alabama. AB - Four species of ticks were collected from 537 white-tailed deer (Odocoileus virginianus), examined during the hunting seasons (November to January) of 1988 89 and 1989-90 at selected locations in Alabama (USA). Ixodes scapularis was the most common tick recovered (2,060 specimens) and infested 54% of the deer. Dermacentor albipictus was the second most frequent tick (1,253 specimens) and infested 15% of the deer. Amblyomma americanum was the third most frequent tick (315 specimens) and infested 24% of the deer; this was the only species of tick collected from deer at all sampling locations. Amblyomma maculatum was an infrequent parasite (five specimens) and infested only 1% of the deer; this tick species was only recorded during the 1989-90 season. Year-to-year and geographical differences in tick infestation parameters were noted. The data are compared with those reported for previous surveys of ticks infesting white-tailed deer in Alabama and adjacent states. PMID- 1758027 TI - Coccidiosis as a cause of transmural lymphocytic enteritis and mortality in captive Nashville warblers (Vermivora ruficapilla). AB - Transmural lymphocytic enteritis was diagnosed in thirteen Nashville warblers (Vermivora ruficapilla) during an epornitic with high mortality. In the intestinal lesions, asexual stages of coccidia were present within lymphocytes and asexual and sexual stages of coccidia were present within intestinal villar epithelium. Ultrastructurally, the infiltrating lymphocytes resembled granular ("intraepithelial") lymphocytes, a cell known to be important in the life cycle of some avian coccidia. Gross and histopathologic features of this enteritis resemble intestinal changes described for Isospora/Atoxoplasma spp. in other passeriformes and lymphoproliferative disease in gold-finches. PMID- 1758028 TI - Gray wolf density and its association with weights and hematology of pups from 1970 to 1988. AB - We examined weights and hematologic profiles of gray wolf (Canis lupus) pups and the associated wolf density in the east-central Superior National Forest of northeastern Minnesota (USA) during 1970 to 1988. We collected weight and hematologic data from 117 pups (57 females, 60 males) during 1 September to 22 November each year. The wolf density (wolves/800 km2) trend was divided into three phases: high (72 +/- 7), 1970 to 1975; medium (44 +/- 2), 1976 to 1983; and low (27 +/- 2), 1984 to 1988. Wolf numbers declined (P = 0.0001) 39 and 63% from 1970 to 1975 to 1976 to 1983 and from 1970 to 1975 to 1984 to 1988, respectively. Weight was similar between male and female pups and did not vary as wolf density changed. Mean hemoglobin (P = 0.04), red (P = 0.0001) and white blood cells (P = 0.002), mean corpuscular volume, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin (P = 0.0001) did differ among the multi-annual phases of changing wolf density. Weight and hematologic data also were compared to values from captive wolf pups. The high, but declining wolf density was associated with macrocytic, normochromic anemia in wolf pups, whereas the lowest density coincided with a hypochromic anemia. Although hematologic values show promise for assessing wolf pup condition and wolf population status, they must be used cautiously until data are available from other populations. PMID- 1758029 TI - Weights and hematology of wild black bears during hibernation. AB - We compared weights and hematological profiles of adult (greater than 3-yr-old) female black bears (Ursus americanus) during hibernation (after 8 January). We handled 28 bears one to four times (total of 47) over 4 yr of varying mast and berry production. Mean weight of lactating bears was greater (P less than 0.0001) than that of non-lactating females. White blood cells (P less than 0.05) and mean corpuscular volume (P = 0.005) also differed between lactating and non-lactating bears. Hemoglobin (P = 0.006) and mean corpuscular hemoglobin concentration (P = 0.02) varied among years; values were lowest during 1975, following decreased precipitation and the occurrence of a second year of mast and berry crop shortages in a three-year period. Significant (P less than 0.05) interaction between reproductive status (lactating versus non-lactating) and study year for hemoglobin, red blood cells, and packed cell volume, and increased mean corpuscular volume, suggested a greater nutritional challenge for lactating females compared to non-lactating females during the 1975 denning season. Our data suggest that hematological characteristics of denning bears may be more sensitive than weights as indicators of annual changes in nutritional status; however, other influential factors, in addition to mast and berry crop production, remain to be examined. PMID- 1758030 TI - Hematology and serum chemistry of cottontail rabbits of southern Illinois. AB - In 1983 and 1984 blood was collected from 79 cottontail rabbits (Sylvilagus floridanus) confined to an outdoor enclosure in southern Illinois to establish reference values for hematology and serum chemistry. Packed cell volume, sodium, potassium, chloride, glucose, calcium, carbon dioxide, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, bilirubin, alkaline phosphatase, aspartate transaminase, alanine aminotransaminase, total protein, albumin/globulin ratio, and osmolality were measured. Sex and age (adult versus juvenile) of rabbit as well as season (June to September versus October to May) and method of capture (trap versus shot) variously affected most hematology and serum chemistry variables. PMID- 1758031 TI - Potential natural exposure of Mississippi sandhill cranes to aflatoxin B1. AB - A survey was conducted to determine if carcinogenic mycotoxins were present in foods consumed by Mississippi sandhill cranes (Grus canadensis pulla). Samples of field corn (Zea mays) (n = 111) and chufa (Cyperus esculentus) (n = 20), obtained in 1987, 1988 and 1989 on the Mississippi Sandhill Crane National Wildlife Refuge (MSCNWR) and nearby private lands were analyzed for aflatoxin B1(AB1), ochratoxin A and sterigmatocystin using thin layer chromatography. Chufa samples were negative for all three mycotoxins. Aflatoxin B1 was found in corn at concentrations from 5 to 5,000 ppb; the other mycotoxins were not found in corn. Contaminated corn was found in 72% of all corn fields, but the proportion of contaminated fields was 57 to 100% for the 3-yr period. Contamination with AB1 was greatest in corn obtained from the ground post-harvest. Overall, 32% of corn samples from the ground had levels greater than or equal to 200 ppb with a mean of 427 ppb (range = 5 to 5,000 ppb) in contaminated fields. In 1989, mean AB1 concentration in corn on the ground was 5 to 1138 ppb for individual fields. The concentration of AB1 was less than or equal to 200 ppb in all corn samples from upright stalks. The study demonstrated that AB1 is available to sandhill cranes and at levels that may pose a serious health threat. PMID- 1758032 TI - A survey of koala road kills in New South Wales. AB - Between 1984 and 1990, 75 koalas (Phascolarctos cinereus) from the central northern coast of New South Wales (Australia) were presented for necropsy due to motor vehicle accidents. The koalas consisted of 44 males and 31 females. Fifty one of these were between 2 and 7 yr (39 males and 12 females). The greater proportion of koalas, especially males, were struck by vehicles between June and December. The main injuries detected were head injuries (44), hemoperitoneum (16), limb injuries (16), hemothorax (15) and spinal injuries (7). Nine koalas were not dead at the time of the accident but died later following complications from the trauma. Twelve koalas had evidence of underlying disease at the time of accident. Ten of these had either conjunctivitis, cystitis, prostatitis, periovarian cysts, endometritis or a combination of the diseases. All 10 koalas still had good body condition. It is suggested that healthy young to middle-aged males are particularly prone to vehicular accidents during the mating period. This has implications for the management of local koala populations. PMID- 1758033 TI - A review of diseases of parasites of the Kafue lechwe (Kobus leche kafuensis). AB - The diseases of the Kafue lechwe (Kobus leche kafuensis) are reviewed in this paper. Kafue lechwe are an important natural resource for Zambia. Bovine tuberculosis is widespread within the lechwe population and they are host to many parasites, especially the warble Strobiloestrous vanzyli. PMID- 1758034 TI - Oral vaccination of skunks with raccoon poxvirus recombinants expressing the rabies glycoprotein or the nucleoprotein. AB - Twenty nine skunks (Mephitis mephitis) were vaccinated orally with raccoon poxvirus (RCN) recombinants: 10 with a recombinant expressing the rabies virus glycoprotein (RCNRG), 10 with RCNRG mixed with a recombinant expressing the rabies virus nucleoprotein (RCNRN) and nine with RCN alone. Rabies virus neutralizing antibodies were detected in six of the 20 skunks; five skunks (three given RCNRG, two given a mixture of recombinants) survived a rabies challenge that was lethal for nine skunks vaccinated with RCN alone. PMID- 1758035 TI - Taxon 20 (Fam. Pasteurellaceae) infections in European brown hares (Lepus europaeus). AB - Hemolytic bacteria, phenotypically related to organisms previously identified as Pasteurella haemolytica and tentatively named Taxon 20, were isolated from cases of purulent bronchopneumonia and from conjunctivitis in European brown hares (Lepus europaeus). The bronchopneumonia, sometimes accompanied by lesions in other organs, occurred without other concomitant disease. The conjunctivitis was found mainly in animals suffering from the European brown hare syndrome. PMID- 1758036 TI - A Sarcocystis sp.-like protozoan and concurrent canine distemper virus infection associated with encephalitis in a raccoon (Procyon lotor). AB - A raccoon (Procyon lotor) with signs of weakness was captured in upstate New York (USA). Despite attempted care in a rehabilitation facility, the animal died and was examined because of suspected infectious neurologic disease. The cerebrum had a marked, locally extensive, neutrophilic, necrotizing encephalitis with numerous associated intralesional protozoal organisms, and a moderate to marked multifocal perivascular nonsuppurative meningoencephalitis. Based on morphology and immunohistochemical staining, the organism was a Sarcocystis sp.-like protozoan. Rabies antigen and canine distemper virus (CDV) inclusions were not detected. However, the animal was positive for canine distemper virus based on peroxidase anti-peroxidase staining. PMID- 1758037 TI - Some viral and protozool diseases in the European wildcat (Felis silvestris). AB - Ten European wildcats (Felis silvestris) were examined at necropsy and an additional 23 were examined clinically for evidence of viral diseases in Scotland. Two plasma samples taken from live free-living wildcats showed positive ELISA reactions to feline leukemia antigen. A feline leukemia virus of subgroup A was isolated from one of these samples, taken from a wildcat in north-western Scotland. No antibodies to feline coronavirus or feline immunodeficiency virus were detected in any sample. Three of the live wildcats and one of the dead had chronic mucopurulent rhinotracheitis suggestive of "cat flu." One other dead wildcat had diffuse enlargement of anterior lymph nodes. The findings indicated that feline leukemia virus infection can occur in free-living Felis silvestris. It is possible that the disease exists as a sustained infection in some wildcat populations, although the close interaction between wildcat and the domestic cat means that the latter could act as a continual source of infection. PMID- 1758038 TI - Coccidiosis in common wombats (Vombatus ursinus). AB - Eimeria arundeli is a widespread coccidian parasite of the common wombat (Vombatus ursinus), and has been considered to be nonpathogenic. We describe disease in two captive juvenile wombats ascribed to infection with E. arundeli. One animal had diarrhea, the second had mucoid soft feces and lost weight over several weeks prior to death. Masses of coccidial gametocytes in hypertrophic cells in the lamina propria distended villi, causing grossly visible raised pale thickened regions over extensive areas of the mucosa of the small intestine in both animals. Neutrophils infiltrated affected mucosa, and there was an inflammatory exudate into the intestinal lumen in case one. In case two, neutrophils infiltrated the lamina propria of villi focally, crypts were distended by necrotic debris, and epithelium on villi was extremely attenuated. No bacterial pathogens were isolated from lung and intestine in case one; case two was not cultured. Oocysts consistent with E. arundeli were present in large numbers in floatations of diarrheic feces in both cases. PMID- 1758039 TI - Haematozoa of fishes in Humboldt Bay, California. AB - Five hundred seven fish representing 45 species from Humboldt Bay, California (USA) were examined for blood parasites. Four fish (less than 1%) from two species were infected. Haemogregarina leptocotti sp. n. is described from one of 33 staghorn sculpin (Leptocottus armatus). Haemogregarina roelofsi sp. n. is described from three of 15 black rockfish (Sebastes melanops). Gametocytes of H. leptocotti sp. n. averaged 6.1 x 2.1 microns with a 2.7 x 1.7 microns oval nucleus; those of H. roelofsi sp. n. averaged 5.5 x 2.7 microns with a 2.5 x 2.2 microns rectangular nucleus. Neither species of parasite had distinct chromatin granules, a polar cap, or more than one gametocyte in an infected cell. Haematozoa are relatively rare in fishes of the northeastern Pacific Ocean. PMID- 1758040 TI - Nasitrema sp.-associated encephalitis in a striped dolphin (Stenella coeruleoalba) stranded in the Gulf of Mexico. AB - An immature female striped dolphin (Stenella coeruleoalba) found dead on a northwestern Florida beach in 1988 exhibited severe inflammation bilaterally in the dorsal and mid-thalamus in association with adult trematodes (Nasitrema sp.) and trematode eggs. Numerous specimens of Nasitrema sp. also were present in the pterygoid sinuses. Pneumonia in association with a heavy growth of Vibrio damsela was observed also. This report confirms the occurrence of Nasitrema sp. associated encephalitis in striped dolphins and in small cetaceans from the Gulf of Mexico. PMID- 1758041 TI - Monthly prevalences of Physaloptera retusa in naturally infected Yarrow's spiny lizard. AB - The gastrointestinal tracts of 167 of 489 (34%) Yarrow's spiny lizards (Sceloporus jarrovii jarrovii) collected in Pima County, Arizona (USA) from October 1967 through January 1970 were infected with Physaloptera retusa. Of the infected lizards, 88 (18%) had only larvae, 45 (9%) had larvae and adults and 32 (7%) had only adult nematodes. The ratio of larval nematodes to adults was approximately 8:1. Monthly prevalences varied from 71% in April 1969 to 10% in July 1969; seasonal patterns of infection were not observed. PMID- 1758042 TI - Survey for meningeal worm (Parelaphostrongylus tenuis) and ear mites in white tailed deer from northern Idaho. AB - During the fall hunting season of 1990, 95 white-tailed deer (Odocoileus virginianus) heads were collected from hunters in Boundary and Bonner Counties in northern Idaho (USA), an area currently occupied by woodland caribou (Rangifer tarandus caribou). The heads were examined for adult and larval meningeal worms (Parelaphostrongylus tenuis) by physical examination of the brain surfaces, and the Baermann technique, respectively, and for ear mites by examination of ear scrapings. Meningeal worms or mites were not detected. PMID- 1758043 TI - Duration of attachment by mites and ticks on the iguanid lizards Sceloporus graciosus and Uta stansburiana. AB - Duration of attachment was determined for the mites Neotrombicula californica and Geckobiella texana and the tick Ixodes pacificus on the iguanid lizards Sceloporus graciosus and Uta stansburiana from southern California. Neotrombicula californica infestations lasted approximately 1 wk. Attachment of Ixodes pacificus larvae and nymphs lasted approximately 8 days on S. graciosus and 16 days on U. stansburiana. Geckobiella texana remained attached to S. graciosus for 5 days and to U. stansburiana for 28 days. PMID- 1758044 TI - Notoedric acariasis in the porcupine (Erethizon dorsatum). AB - Six of 16 porcupines (Erethizon dorsatum) live-trapped in Sullivan County, Pennsylvania were infested with the mite Notoedres douglasi. Alopecia was evident in the ventral inguinal area and the infested skin was thickened, wrinkled and had multifocal areas of extensive hyperkeratosis. Microscopically the skin lesions consisted of extensive acanthosis and hyperkeratosis with variable cellular infiltrate in the dermis. Mites were seen in tunnels in the hyperkeratotic skin sections. This is the first report of notoedric acariasis in the porcupine. PMID- 1758045 TI - First record of Ixodes brunneus in Kansas. AB - A single specimen, a partially engorged female, of Ixodes brunneus was recovered from a common grackle (Quiscalus quiscula) in Butler County, near El Dorado, Kansas (USA). The discovery of this tick in Kansas represents a new state record. PMID- 1758046 TI - On the use of xylazine for field immobilization of bighorn sheep. PMID- 1758047 TI - [Effects of erythroid differentiation factor on inhibition of erythroid colony formation (CFU-E and BFU-E) by the sera and on BPA secretion by peripheral mononuclear cells in patients with chronic renal failure]. AB - The effect of erythroid differentiation factor (EDF) on the colony formation of erythroid cells (CFU-E and BFU-E) inhibited by the sera from the patients with chronic renal failure (CRF) was evaluated by methylcellulose assay. EDF restored the inhibited formation of CFU-E colony irrespective of the absence or presence of the accessory cells. In addition, EDF was considered to recover BFU-E colony formation through the burst promoting activity (BPA) secreted by the adherent cells. A suicide experiment using 3H-thymidine revealed that EDF acted to induce BFU-E from resting phase to S phase of the cell cycle. Moreover, the number of circulating BFU-E and the secretion of BPA by the mononuclear cells, both of which were significantly low in CRF patients, were also moderately increased by the addition of EDF. These data suggest that EDF could be utilized as a therapeutic agent for pathogenetic factors except hypoproduction of erythropoietin on the anemia of the patients with CRF. PMID- 1758048 TI - [Combination chemotherapy of advanced Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone]. AB - Thirty-three patients with advanced Hodgkin's disease were treated with a combination chemotherapy consisting of vincristine 1 mg/m2 iv on day 1, 8, cyclophosphamide 500 mg/m2 iv on day 1, procarbazine 100 mg/m2 p.o. day 1-7, and prednisolone 40 mg/m2 p.o. day 1-7. Twenty patients received this regimen every 4 weeks (VCPP II regimen). Furthermore, we conducted higher dose intensive VCPP II 2 regimen which was repeated every two weeks for thirteen patients. Complete response rate of both regimens was 63% (VCPP II 45%, VCPP II-2 85%). The median duration of CR was 37 + months. Leukopenia, neurotoxicity and gastrointestinal toxicity were commonly observed but were clinically manageable. These results indicate that high dose intensive chemotherapy is effective for achieving high CR rate for advanced Hodgkin's disease. PMID- 1758049 TI - [Peripheral blood stem cell autografts (PBSCT) in the treatment of 30 children with acute leukemias and lymphoma]. AB - Thirty children (1-16 y.o.; median, 10 y.o.) with acute leukemia or non-Hodgkin's lymphoma (NHL) associated with high-risk features underwent high-dose chemotherapy without total body irradiation and peripheral blood stem cell autografts (PBSCT). Eighteen patients had acute lymphoblastic leukemia (ALL), 6 had acute non-lymphoblastic leukemia (ANLL), 2 had mixed-lineage leukemia and 4 had NHL. Twelve patients with two or more high-risk features (WBC greater than 10 x 10(4)/microliter, T- or B-phenotypes, infancy, massive organ infiltration, or induction failure) underwent PBSCT in 1st CR. Twelve patients underwent PBSCT in 2nd CR, and 4 in the subsequent remission greater than or equal to 3rd CR). Two patients were treated at refractory relapse. After PBSCT the number of days required to achieve a granulocyte count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l was 6.39 (median, 13) and 9-427 (median, 16), respectively. The disease-free survival rate was 6/12 in 1st CR group (6-41 mo) and 6/16 in the patients who underwent PBSCT in 2nd or subsequent remission (2-35 mo). The data justify the incorporation of PBSCT in the design of salvage protocol for children with leukemias or NHL. However, the application of the procedure as part of initial therapy in patients still remaining in 1st CR should be regarded as highly experimental and deserve further clarification. PMID- 1758050 TI - [The analysis of leukemic relapse after allogeneic bone marrow transplantation]. AB - This report presents the analysis of leukemic relapse of 52 patients who received allogeneic bone marrow transplantation between July 1984 and May 1990. Conditioning regimen consisted of TBI + CY and GVHD prophylaxis consisted of cyclosporin-A and methotrexate. The relapse ratios of chronic myelogenous leukemia (CML) (21 in chronic phase, 1 in accelerated phase, 1 in blastic crisis), acute nonlymphocytic leukemia (ANLL) (all 17 in 1st CR), acute lymphocytic leukemia (ALL) (all 12 in 1st CR) were 13%, 18%, 25%, respectively, and 3 year disease free survival (DFS) was as follows, CML 68%, ANLL 72%, ALL 49%. Regarding acute GVHD grading and chronic GVHD presence, 3 year DFS was as follows, acute GVHD 0 degree: 59%, I degree: 78%, II degree-IV degree: 53%, chronic GVHD (+): 82% GVHD (-): 77%. In our center leukemic relapse has been the major cause of death after BMT since 1984. Among 9 relapsed cases, one recurred more than 3 years after BMT, and another one got recurrent leukemia of donor origin. PMID- 1758051 TI - [Requirements of diagnostic criteria for aplastic anemia in children]. AB - As a general rule, diagnostic criteria of aplastic anemia in children are the same as adult criteria. However, blood counts of normal children show wide age related variation, therefore we must establish a system of adjustment for diagnosis of aplastic anemia in children. The data of children with aplastic anemia visiting our institutes from 1966 to 1990 were evaluated for this study. RBC below 350 x 10(4)/microliters, WBC below 4,000/microliters or neutrophils below 1,500/microliters, platelets below 8 x 10(4)/microliters, reticulocytes below 4 x 10(4)/microliters and lymphocytes over 60% were seemed to satisfy the diagnostic criteria of aplastic anemia proposed by the Study Group of hemopoietic Disorders sponsored by the Ministry of Health and Welfare of Japan. Fifteen children (4.6%) did not meet these criteria and as such were diagnosed as atypical aplastic anemia. Thirteen of them were in a pre-aplastic state and developed typical aplastic anemia within 6 months to 8 years after the initial diagnosis. Clinical findings of these patients showed the decrease in number of megakaryocytes and committed stem cells in bone marrow. Three of these patients developed acute non-lymphocytic leukemia, and 2 of them were diagnosed as Fanconi's anemias. PMID- 1758052 TI - [Myelodysplastic syndrome in a patient with familial Pelger-Huet anomaly]. AB - This paper reports on a patients with congenital Pelger-Huet anomaly who developed myelodysplastic syndrome (MDS). A 45-year-old female was referred for investigation of pancytopenia of 6 months' duration. Hereditary Pelger-Huet anomaly was diagnosed by family study 7 years prior to admission. On admission, Hb was 6.5 g/dl, Ht 19.9%, Platelets 1.8 x 10(4)/microliters, and WBC 1,200/microliters with 2% myelocytes, 9% metamyelocytes, 14% bands, 2% segmented neutrophils, 58% lymphocytes and 5% monocytes. Most of the granulocytes were Pelger-Huet type with strikingly clumped nuclear chromatin. Bone marrow aspirate demonstrated 3.6% blasts and dysplastic changes including megaloblastoid features in erythroid series and micro-megakaryocytes compatible with refractory anemia, a subtype of MDS. The association of hereditary Pelger-Huet anomaly and MDS is discussed. PMID- 1758053 TI - [A high serum level of interleukin-6 in a patient with aggressive multiple myeloma]. AB - A 58-year-old female was admitted to our hospital because of anemia in March 1987. Monoclonal protein (IgA, kappa) was detected and a diagnosis of multiple myeloma was made. Partial remission was obtained after VAD therapy with alpha interferon. In December 1989, she was readmitted because of a pathological fracture of the left humerus. A white blood cell count was 4400/microliters with 30% myeloma cells and the urine protein (Bence Jones protein) was 26 g/day. Systemic chemotherapy was not effective. She developed pleural and pericardial effusions, bone mass, disturbance of consciousness and died of respiratory failure only 3 months after readmission. The pleural and pericardial fluids contained many myeloma cells. c-myc gene rearrangement was detected in myeloma cells obtained from the pleural fluid using c-myc exon1 and exon2 probes. The levels of interleukin-6 (IL-6) measured by ELISA was 107.4 pg/ml in serum, 56.2 pg/ml in pleural fluid and 780.0 pg/ml in pericardial fluid. Because of the lack of any overt infectious focus, the level of IL-6 appears to have been related to aggressive proliferation of myeloma cells. It was of interest that C-reactive protein, induced by IL-6, was a good marker reflecting disease activity. PMID- 1758054 TI - [Temporary spontaneous remission in Ki-1 (CD30) lymphoma with gastric lesion]. AB - A case of 56 year-old man with Ki-1 (CD30) lymphoma is reported. He noticed cervical lymph node swelling and was admitted with temporary diagnosis of gastric adenocarcinoma in February 1986. His physical examination showed several from 1 to 4 cm size enlarged cervical and axillary lymph nodes. His first lymph node biopsy demonstrated the histological picture of malignant lymphoma. After 20 days his second lymph node biopsy demonstrated the picture of necrosis. Second gastric biopsy showed the picture of neither gastric cancer nor malignant lymphoma, in spite of his first gastric biopsy finding with adenocarcinoma that turned out to be malignant lymphoma by later reinvestigation. After word those lymph nodes disappeared and have not been palpable for about ten months. In October 1987, elevated LDH value, lymph node swelling and gastric lesion were again observed and sixth gastric biopsy demonstrated the picture of malignant lymphoma. He was treated with anti-lymphoma drugs. After his partial remission, he died of gastrointestinal bleeding in April 1988. Specimens of both first lymph node biopsy and sixth gastric biopsy were examined with cell markers for infiltrated cells and were positive for Ki-1/Ber-2H. His final diagnosis was Ki-1 lymphoma. PMID- 1758055 TI - [Application of Y-chromosome specific DNA analysis for detection of mixed hematopoietic chimerism after allogeneic bone marrow transplantation]. AB - We report a case involving mixed hematopoietic chimerism after an allogeneic bone marrow transplantation (BMT) from a sex mismatched donor. A 31 year-old-man who was diagnosed as having chronic myelogenous leukemia in the accelerated phase received an allogenic BMT from his HLA-identical sister in March, 1989. To determine the mixed chimerism we used the Y-chromosome specific repeated sequence of DNA using a specific probe (PHY 10). The donor's DNA 3.5 kb band appeared in 1 10% of male DNA by Southern blot hybridization in the peripheral blood 21 days after BMT. The Y-chromosome DNA band decreased day by day, and disappeared 110 days after BMT. The Y-chromosome DNA band could be detected, even though few metaphases were obtained immediately after BMT. Thus this method is very sensitive for determining which cells contain the Y-chromosome, and is therefore useful for detecting mixed chimerism after sex-mismatched BMT. Using this method the clinical significance of mixed chimerism can be assessed. PMID- 1758056 TI - [Acute megakaryoblastic leukemia with leukemia cutis, meningeal leukemia, and myelofibrosis]. AB - A 64-year-old man was admitted to our hospital with leukopenia. On admission, leukocyte count in the peripheral blood was 1,600/microliters, containing 24.5% blasts of lymphoid appearance, which were negative for myeloperoxidase. A bone marrow aspiration showed hypoplasia with increased blasts (31.6%). The blasts were ultrastructurally positive for platelet peroxidase (PPO) and positive for platelet membrane glycoprotein IIb/IIIa complex. A diagnosis of acute megakaryoblastic leukemia was made. Chemotherapy with behenoyl-ara C (BH-AC) (150 mg/day) was transiently effective. However, after three months, numerous nodules without itching appeared over the entire body, particularly on the anterior chest. A biopsy of the skin lesion revealed a diffuse fibrosis with infiltrations of the blasts. Bone marrow aspirations were dry tap, and a bone marrow biopsy showed marked myelofibrosis. Then, severe headache, vomiting, and loss of consciousness developed, and a lumbar puncture revealed infiltrations of blasts. Although methotrexate was intrathecally injected, he died due to the respiratory failure. As far as we know, a case of acute megakaryoblastic leukemia with leukemia cutis and meningeal leukemia is quite rare. In addition, it is interesting that megakaryoblastic leukemia was accompanied with both the fibrosis of skin and the myelofibrosis. PMID- 1758057 TI - [Primary myelofibrosis transforming into multiple subcutaneous monoblastoma--a case report]. AB - A 83-year-old man was diagnosed with primary myelofibrosis based on the presence of leukoerythroblastosis, splenomegaly, chromosome 46 XY, a dry tap bone marrow aspiration and fibrosis on bone marrow biopsy, when he was admitted for herpes zoster in June 1987. He was admitted for a second time with multiple subcutaneous tumors over his entire body in July, 1989. He had mild splenomegaly, but no hepatomegaly nor lymphadenopathy. Laboratory tests were as follows: RBC 214 x 10(4)/microliters, Hb 5.1 g/dl, Ht 17.7%, WBC 3,200/microliters with leukoerythroblastosis, platelets 11.6 x 10(4)/microliters, s-lysozyme 251 micrograms/ml, u-lysozyme 770 micrograms/ml, NAP ratio 98%, score 278. Bone marrow aspiration resulted in a dry tap. Bone marrow biopsy showed marked fibrosis. Histologic examination of subcutaneous tumor biopsy specimens revealed a diffuse infiltration of monocytes with flexuous nuclei. These cells were positive for alpha-naphtyl butyrate esterase stain, and negative for peroxidase, alpha-naphtol ASD chloroacetate esterase stain and platelet glycoprotein IIb/IIIa stain (APAAP). Ultrastructurally, these cells were mostly monocytes and promonocytes, while phenotypically, CD11b, CD13, CD14, CD33 and HLA-DR were positive. These date indicated that the subcutaneous tumors originated from monocytes. PMID- 1758058 TI - [Blastic form of acute erythremia: report of an autopsy case]. AB - We report an autopsy case of acute erythremia which terminated in generalized infiltration of immature blasts similar to proerythroblasts. A 61-year-old man was admitted because of general fatigue and fever in June, 1990. Mild anemia and severe thrombocytopenia were noted. The bone marrow was hypocellular with 25.5% blasts similar to proerythroblasts and 36.5% erythroblasts, many of which were polynuclear and megaloblastoid. The blasts were cytochemically negative for POX, but positive for PAS staining. Therefore he was diagnosed as having acute erythremia. Partial remission was achieved by BHAC-EV therapy. But three months later, his marrow was replaced by 52.7% blasts as seen in admission. Those blasts were negative for lymphoid, myelocytic, megakaryocytic markers and antiglycophorin A, but positive for OKT 9. Electron microscopy revealed that some of blasts had characteristics of immature erythroblasts. In spite of low dose Ara C therapy, he died of sudden gastrointestinal bleeding in December, 1990. The autopsy disclosed widespread infiltration of blasts, involving liver, spleen, lung, kidney and stomach. It was interesting that dysplasia had been confined to erythroid lineage throughout his clinical course. He seemed to be a rare case of blastic form of acute erythremia which should be distinguished from erythroleukemia. PMID- 1758059 TI - [Primary bilateral adrenal lymphomas in 3 cases]. AB - This report describes three of primary bilateral adrenal lymphoma. Case 1 was an 87-year-old female. She was admitted to our hospital because of anemia. Masses in the bilateral adrenal glands were noted on abdominal computed tomography (CT). After combination chemotherapy, bilateral adrenal masses transiently showed a remarkable reduction, but they soon enlarged and she died. The pathological diagnosis at autopsy was non-Hodgkin lymphoma (diffuse medium sized cell type). Case 2 was a 77-year-old male. He visited our hospital complaining of general malaise. Masses in the bilateral adrenal glands were noted on abdominal CT and he was admitted. The left adrenal was biopsied under echo guidance. The pathological diagnosis was non-Hodgkin lymphoma (diffuse medium sized cell type). The bilateral adrenal masses transiently responded to combination chemotherapy, but soon enlarged again and he died. Case 3 was a 75-year-old male. He visited our hospital complaining of general malaise. Masses in the bilateral adrenal glands was noted on abdominal CT and he was admitted. The left adrenal was biopsied under echo guidance. The pathological diagnosis was non-Hodgkin lymphoma (diffuse medium sized cell type). Combination chemotherapy was followed by a complete remission and discharge of the patient. PMID- 1758060 TI - [Adult type of idiopathic paroxysmal cold hemoglobinuria]. AB - A 78-year-old female suffered from idiopathic paroxysmal cold hemoglobinuria (PCH). Her symptom occurred immediately after she worked outside in the cold early morning. This case is characterized by the eldest case with non-syphilitic PCH reported in Japan and by the most advanced anemia (Hb 4.2 g/dl) possibly due to prolonged hemolysis after cold exposure. Analysis of the serum revealed positive Donath-Landsteiner antibody of IgG type, which could react to hemolysis not only below 15 degrees C but also at 15-20 degrees C in vitro. PMID- 1758061 TI - [Clinical evaluation of severe toxicity in two patients with acute lymphoblastic leukemia receiving outpatient methotrexate therapy]. AB - Methotrexate (MTX) is now widely used for the treatment of acute leukemia and non Hodgkin lymphoma in the pediatric oncology field and is thought to be one of the key drugs for this treatment. A regimen utilizing high dose MTX (HD-MTX) with leucovorin rescue is being investigated as effective chemotherapy in the patients with these kinds of cancer. Relatively large amounts of MTX (225 mg/m2) are given to such outpatients by intravenous push as a course of maintenance therapy. It is said that those amounts will infuse safely. However, we experienced two serious cases-patients T.H. and M.Y.--which developed into severe side effects after this treatment. Both patients showed acute renal failure, severe myelosuppression, erosion around the oral and anal region, and continuous diarrhea. Judging from the serum concentration of MTX, patient T. H. was exposed to more than the maximum allowance serum MTX level for 9.6 days, patient M. Y. for 6.5 days. This suggests physicians must pay attention to the clinical symptoms even after treatment using MTX without HD-MTX. PMID- 1758062 TI - [Myelodysplastic syndrome with neoplastic angioendotheliosis: report of a case]. AB - A 62-year-old woman was admitted to our hospital because of general malaise in May, 1987. No hepatosplenomegary, skin eruption or lymphadenopathy was detected. Laboratory examinations showed mild anemia, thrombocytopenia, normal leukocyte count with no lymphocyte abnormality, hypogranular neutrophils, elevated serum lactic dehydrogenase, increased C-reactive protein and hypoxia. Bone marrow aspirate was normocellular with dysplastic changes in erythroid and megakaryocytic lines which agree with a diagnosis of myelodysplastic syndrome (MDS). She was treated with prednisolone which relieved her symptom but she developed high fever, hemiplegia and disturbance of consciousness and died in August, 1987. Necropsy of the kidney revealed large mononuclear cells within the lumen of small blood vessels. Immunohistochemical study of these malignant cells showed positive reaction to the anti-LCA and anti-L26 antibodies. And electron microscopy showed no azure granules in these cells. Then we diagnosed as neoplastic angioendotheliosis (NAE). To our knowledge, this is the first report of NAE with abnormalities in myeloid, erythroid and megakaryocytic lineages. These results suggest that NAE with MDS originate from a multipotent stem cell. PMID- 1758063 TI - [Successful cholecystectomy in a patient with paroxysmal nocturnal hemoglobinuria]. AB - We report a case of paroxysmal nocturnal hemoglobinuria (PNH) and review the literature regarding transfusion of red blood cells in PNH patients. A 42-year old woman with myelodysplastic syndrome (MDS) complaining of right hypochondralgia and high fever was admitted to the hospital for acute cholecystitis with gall stone. Blood examination revealed bicytopenia (leukocytes, 1,700/microliters and hemoglobin, 8.5 g/dl) and bone marrow examination showed normocellular but hypererythroid bone marrow and dyshematopoiesis, which suggested MDS. Laboratory data revealed obstructive jaundice and hemolytic anemia. Positive sucrose and Ham tests, which were compatible with the diagnosis of PNH. Cholecystectomy was successful, and the patient showed no postoperative complications of increased hemolysis or thrombosis. As hemoglobin level gradually decreased for the first two postoperative weeks, filtrated white cell-depleted red blood cells (total, 1,000 ml) were transfused instead of washed red blood cells. No side effects of the transfusion were noted. On the basis of findings in this case and those reported in the literature, it is concluded that in some case of PNH, the use of washed red blood cells is unnecessary, and that the use of white cell-depleted red blood cells is indicated. PMID- 1758064 TI - [Hodgkin's disease associated with LDH-M subunit deficiency]. AB - The patient was a 60-year-old man who had complained of left cervical swelling from the end of June, 1984. He was diagnosed as having Hodgkin's disease (mixed cell type) by lymph node biopsy, and was admitted to our hospital for thorough examination and treatment on July 23rd. Diagnosis of stage IA Hodgkin's disease involving only the left cervical lymph node was made. On admission, laboratory data revealed that the LDH activity in his serum and erythrocytes consisted of only type 1 (LDH-H4), hence LDH-M subunit deficiency (homogeneous type) was diagnosed. However, the muscle rigidity, myoglobinuria, and skin lesions that are usually seen in this abnormality were not observed. After two course of C-MOPP therapy, beginning on August 1st. complete remission was obtained. He was subsequently given a total of 6 courses of C-MOPP therapy and 40 Gy of irradiation on an outpatient basis. He eventually died of heart failure on November 3rd, 1986. Only five families with LDH-M subunit deficiency have been reported to date in Japan. This is the first report in Japan of the condition being complicated by Hodgkin's disease. PMID- 1758066 TI - [Biological membranes and blood cells]. PMID- 1758065 TI - [Dynamic structure and function of biological membranes]. PMID- 1758067 TI - [Functional role of cell surface glycoconjugates in leukemic cell differentiation: a specific type of sialoglycosphingolipids (gangliosides) as potent differentiation-inducers for human myelogenous leukemia cells]. PMID- 1758068 TI - [Ultrastructure of the plasma membrane of blood cells]. PMID- 1758069 TI - [Function and pathophysiology of platelet membrane glycoproteins]. PMID- 1758070 TI - [Lipid metabolism of platelet membrane]. PMID- 1758071 TI - [Surface antigens of megakaryocytes]. PMID- 1758072 TI - [The interaction of platelet and vascular endothelial cell]. PMID- 1758073 TI - [Liposomal membrane]. PMID- 1758074 TI - [Medical application of liposomes]. PMID- 1758075 TI - [Development of a new diagnostic assay system using liposomes]. PMID- 1758076 TI - [Peripheral blood film evaluation for the diagnosis of a patient with red cell membrane disorder]. PMID- 1758077 TI - [Changes in erythrocyte membrane fluidity and function in diseases]. PMID- 1758078 TI - [Rheology of blood]. PMID- 1758079 TI - [Inhibition of the cysteamine-induced gastric ulcer by the sympathoadrenal medullary system in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY)]. AB - We previously reported that cysteamine induces severe gastric ulcers in WKY, but very mild in SHR. The aim of this study is to elucidate the role on the sympathoadrenal medullary system in the pathogenesis of the cysteamine-induced gastric ulcer. Catecholamine (CA) contents in the stomach and adrenal gland were significantly higher in the non-treated SHR than in the non-treated WKY, suggesting that the sympathetic nervous system is more facilitated in SHR. Cysteamine decreased the noradrenaline and adrenaline contents in these tissues in both strains, however the values of CA was still higher in the treated SHR than the non-treated WKY. Histologically the adrenal medulla was severely damaged by cysteamine administration in WKY than in SHR. In contrast an immunohistological study revealed that chromogranin reactivity of the adrenal medulla was significantly stronger in the treated SHR than in the treated WKY. The celiac plexus was well preserved morphologically even in the cysteamine treatment in both strains. These results suggest that the capacity of the sympathetic nervous system in both the adrenal medulla and the stomach plays an important role in preventing the cysteamine-induced gastric ulcer in SHR. PMID- 1758080 TI - [A study on the mechanism of indomethacin induced intestinal ulcer--from a viewpoint of unstirred water layer]. AB - We subcutaneously injected indomethacin (IDM) to rats and evaluated its effects on the unstirred water layer (UWL) of the small intestine. One hour after IDM administration at a dose of 4, 10, 20 and 50 mg/kg, the thickness of UWL decreased dose-dependently. Serial measurement of UWL 1, 3, 6, 12 and 24 hours after the administration showed early thinning of UWL after 1-3 hours. Many IDM induced ulcers were shown 24 hours after the injection of IDM at a dose of 10 mg/kg. However, in the group given food during the latter 3 hours between 12 and 15 hours after the drug administration, the number of ulcers was significantly decreased compared with those in the group given food ad libitum or in the group given food during the early 3 hours. When pectin, a soluble dietary fiber, was given together with solid stock food, ulcer formation was significantly inhibited. Synthesis of mucus glycoprotein by tissue organ culture was also decreased in the jejunum in the IDM-treated group. These results suggest that the formation of IDM-induced intestinal ulcer is related to the thing of intestinal UWL and the decrease of the synthesis of intestinal mucus glycoprotein. PMID- 1758081 TI - [Diagnosis of protein-losing gastroenteropathy by 111In-transferrin scanning and fecal excretion test]. AB - A total of twelve patients with gastroenteropathy were studied for possible protein loss. The underlying diseases were intestinal lymphangiectasia, ulcerative colitis and Crohn's disease in 2 patients each; and Menetrier's disease, Cronkhite-Canada syndrome, postgastrectomy syndrome, severe atrophic gastritis, gastric cancer and gastroenteropathy of unknown origin in 1 patient each. The controls used in this study were four healthy volunteer and 9 patients with benign disease not accompanied by lesions in the digestive tract and protein loss, 111In-transferrin (Tf) was prepared by incubating 2-3 mCi of 111In-chloride with 15-20 ml of each patient's plasma in a sterilized vial at room temperature for 1 hour. After i.v. injection of 111In-Tf, the patients were scanned at given intervals of time for 72 hours to localize protein loss. 72-hour fecal 111In-Tf excretion was also measured. The following results were obtained: (1) 111In-Tf was detected in the feces of all patients. The recovery rate in the patient group was 7.95 +/- 3.65%, which was significantly higher than 0.48 +/- 0.26% in the control group (p less than 0.01). (2) However, 111In-Tf scanning showed the site of protein loss only in 6 patients. Negative scan in six other patients was thought to be associated with extensive inflammation and severe diarrhea. (3) Five of the twelve patients were observed before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758082 TI - [Induction of experimental splenomegaly with portal hypertension in rats with liver cirrhosis]. AB - Liver cirrhosis was induced in rats by administering thioacetamide (TAA), and portal hypertension was maintained for at most 35 weeks to study the influence of portal hypertension on the weight of spleen and splenic tissues. TAA was intraperitoneally injected at dose of 200 mg/kg three times a week. The portal pressure was elevated and the weight of the spleen increased with the progression of hepatic fibrosis due to TAA. Liver cirrhosis was obviously observed after TAA was administered 60 times. The maximum ratio of the weight of the spleen to body weight in the group administered TAA was higher by 4.08 times than that in the control group. In all 49 rats used in the experiment there was a high correlation (r = 0.930, p less than 0.01) between the portal pressure and the ratio of spleen to body weight. Histological observation revealed that the red pulp tended to be enlarged, while the white pulp tended to be reduced, with increases in portal pressure and weight of the spleen. It also histologically revealed an increase in the splenic sinus-like structure, narrowing of the splenic cords, fibrosis due to reticular cell proliferation in the red pulp and fibrosis around the central artery in the white pulp. These histological changes in rats were similar to the histological findings of splenomegaly accompanying portal hypertension in humans. This suggests that the animal model prepared in the present experiment is useful as a model of splenomegaly due to portal hypertension. PMID- 1758083 TI - [Effect of synthetic protease inhibitor on the sphincter of Oddi function in dogs]. AB - Fundamental study in dogs have shown that the synthetic protease inhibitor has pharmaceutical properties characterized by effect on motility of the sphincter of Oddi. Synthetic protease inhibitors, gabexate mesilate and nafamostat mesilate have effects on motility of the sphincter of Oddi in dogs. The motor effect of synthetic protease inhibitor on the sphincter of Oddi has been investigated by manometric evaluation. Immediately after intravenous administration of gabexate mesilate (5, 10, 50, and 100 mg/kg/h) the motility of the sphincter of Oddi was inhibited dose-dependently, on the other hand after intravenous administration of nafamostat mesilate (0.5, 1, and 5 mg/kg/h) motility of the sphincter of Oddi was accelerated. Therefore it was suggested that these results shown some considerable problems in clinical use. PMID- 1758084 TI - [Study of patency of minor duodenal papilla--comparison between pigment method combined with pH sensor and pancreatographic method]. AB - We investigated the patency of minor duodenal papilla in 25 cases that had presented normal pancreatogram by using the endoscopic retrograde pancreatographic (ERP) method and a pH sensor-combined indigo carmine pigment method. The pigment method allowed us to classify the function of minor papilla into three types according to pancreatic juice excretion pre- and post-secretin administration (Type I), excretion after secretin administration (Type II), and no excretion even after secretin administration (Type III). Twelve cases belonged to Type I, 4 cases to Type II and 9 cases to Type III. By ERP method, terminal shapes of the Santorini's duct were classified as stick type, cystic type and branch type. 19 cases were considered stick type, 2 cases cystic type and 4 cases branch type. Eighteen cases were identified as patent minor papilla under ERP method. There were two cases alleged to be patent under the ERP but without pancreatic juice excretion. Therefore, the necessity of pigment method was confirmed for investigation of the function of minor papilla. PMID- 1758085 TI - [Three cases of gastric malignant lymphoma with a characteristic endoscopic ultrasonographic appearance]. PMID- 1758086 TI - [A case of "dry form" tuberculous peritonitis with difficult differential diagnosis from pseudomyxoma peritonei]. PMID- 1758087 TI - [A case of primary biliary cirrhosis accompanied by uveitis]. PMID- 1758088 TI - [Two cases of gas-containing liver abscess--review of Japanese literature]. PMID- 1758089 TI - [A case of visceral larva migrans by Toxocara cati infection with multiple liver granuloma]. PMID- 1758090 TI - [A case of inflammatory pseudotumor of the liver]. PMID- 1758091 TI - [Primary early carcinoma of the cystic duct--a case report and review of the literature]. PMID- 1758092 TI - [A case of lipase-secreting acinar cell carcinoma with subcutaneous fat necrosis]. PMID- 1758093 TI - [Hepatic metastasis of serous cystadenocarcinoma resected 4 years after operation of primary tumors--a case report]. PMID- 1758094 TI - [Effect of free radical and experimental study on development mechanism of gastric rupture in newborn]. PMID- 1758095 TI - [Ultrasound image of muscularis mucosae of the stomach]. PMID- 1758096 TI - [Inhibition of gastric acid secretion by protein kinase C in isolated rat parietal cells]. PMID- 1758097 TI - [Effects of protease inhibitors on the motor activity of canine sphincter of Oddi]. PMID- 1758098 TI - [Pancreatic lysosomal enzyme secretion into pancreatic juice stimulated by secretin and caerulein in rabbit]. PMID- 1758099 TI - [Acute pulmonary thromboembolism after coronary artery bypass grafting]. AB - The cases of acute pulmonary thromboembolism after coronary artery bypass surgery have been rarely reported in Japan. We, however, experienced 2 cases of them and lost them against intensive therapy. In Mitsui Memorial Hospital, 6 cases of pulmonary thromboembolism had been diagnosed in 1990 (0.074% in admission patients), four of the cases had occurred following surgical procedures. Its manifestations are deceivingly nonspecific and are difficult to distinguish perioperative myocardial infarction, pericardial tamponade, and pneumothorax, especially in postoperative states. We would like to emphasize that acute pulmonary thromboembolism is getting important problems also in Japan. PMID- 1758100 TI - [The influence of left atrial cuff rejection on pulmonary hemodynamics after canine lung allotransplantation]. AB - Several factors influence pulmonary hemodynamics after lung transplantation: reimplantation response, lung rejection reaction and imperfect anastomosis technique. In this experiment, five cases presented marked elevation of mean pulmonary artery pressure at the time or right pulmonary artery occlusion test performed two weeks postoperatively. Left atrial cuff rejection reaction arose in one case in which edema and stenosis of the pulmonary vein outflow tract were evidenced. This finding demonstrated that the changes in pulmonary hemodynamics after transplant suggest the possibility of inducement by left atrial cuff rejection reaction. PMID- 1758101 TI - [Operative management of the calcified patent ductus arteriosus in the elderly]. AB - Two cases of the calcified PDA were experienced in subjects aged more than 50 years. A 63-year-old woman was successfully operated upon. A Fogarty's balloon catheter was wedged into the PDA through the ductus after a pulmonary arteriotomy under cardiopulmonary (CP) bypass. A 57-year-old woman was safely operated. PDA was repaired under partial CP bypass with Bio-pump. Postoperative courses of these cases were uneventful. Brief review of surgical treatment for PDA was given. PMID- 1758102 TI - [Postoperative brain metastasis from esophageal carcinomas: report of 4 cases]. AB - Out of 83 cases received resection of primary esophageal lesion, 4 patients were affected by metastatic brain tumor which was reported to rarely occur. All 4 patients had symptoms of central nervous system. Three of them were diagnosed by CT and the other one at autopsy. All of the primary esophageal tumors were advanced and of histological stage III or IV. They located in the middle or lower thoracic esophagus. Brain tumor of one case was removed and this case was of progression free at the last presentation. The other 3 cases were not received resection of metastatic brain tumors and died. All of 3 were autopsied and two of them had no metastasis in the lung. Therefore, it was considered that these hematogenic metastases were not through lung filtrations but through other routes, which Batson O. V. experimentally proved and designated as vertebral vein system in 1940. It is concluded that aggressive surgical intervention to metastatic brain tumors was beneficial with regard to prognosis for cases without other metastatic lesions. PMID- 1758103 TI - [Aortitis syndrome associated with aortic regurgitation and coronary ostial stenosis: a case of successful surgical treatment at the active stage]. AB - A 24-year-old woman with aortic regurgitation and ostial stenosis of coronary artery due to aortitis syndrome was reported. She was admitted to the hospital with anterior chest pain. Retrograde aortogram showed aortic regurgitation and selective coronary angiogram revealed severe ostial stenosis. In spite of steroid therapy, chest pain was not controlled. In spite of the active stage, she underwent aorto-coronary bypass and aortic valve replacement. Intra-aortic balloon pumping (IABP) was necessary to wean from cardio-pulmonary bypass, but she recovered well and no complication was recognized after operation. PMID- 1758104 TI - [A case report of cavernostomy for lung aspergilloma]. AB - A 65-year-old male patient with right upper lobe aspergilloma treated surgically due to continuation of hemoptysis was reported. Cavernostomy was indicated in this patient, since he had a low respiratory function. After cavernostomy, cavitry infection with MRSA occurred and additional operation was necessary. We should gave great care to intra-cavitary infection. Loss of lung function after the operation seemed to be minimal. PMID- 1758105 TI - [A case of mediastinal cavernous hemangioma]. AB - A case of mediastinal cavernous hemangioma was reported. An asymptomatic 6-year old girl was discovered to have a mass in the left anterior superior mediastinum on a routine chest x-ray film. Computed tomograms demonstrated a mediastinal mass with calcification. Under a median sternotomy, a 10 x 9 x 5 cm mass was resected after dissecting the connections to the pericardium. As the mass surrounded the left phrenic nerve, the nerve was resected with the tumor. The histopathology was cavernous hemangioma. The calcification was not found in the vessels as the phleboliths but was showed in the interstitial tissues. PMID- 1758106 TI - [Sudden onset of systemic hypoxia associated with both tricuspid regurgitation and persistent foramen ovale: a case report]. AB - A 33-year-old female who had undergone closure of VSD 20 years before, was hospitalized for sudden onset of dyspnea without history of febrile or traumatic disorder. On admission, she had cyanotic lips and nailbeds but no clubbed finger. Chest x-ray film showed neither lung congestion nor cardiomegaly. Arterial blood gas analysis revealed deep hypoxia (PaO2 = 49.6 mmHg). Echocardiogram clarified massive tricuspid regurgitation (TR) due to chordal rupture of anterior leaflet, small VSD jet stream through the membranous aneurysm and a great deal of R-L shunt on the atrial level through a persistent foramen ovale. Cardiac catheterization data confirmed 35% of R-L shunt. At operation, a torn chordal tendon of anterior leaflet and an adhered septal leaflet to aneurysm of membranous portion of ventricular septum were seen. There were two pledgets, used at the first surgery, at the base of the aneurysm and a couple of tiny holes (VSDs) above and below the pledgets were recognized. Following resection of anterior and posterior leaflet, plication of septal leaflet and closure of VSD, a Xenograft valve (Carpentier-Edwards 29-M) was implanted. Then persistent foramen ovale, 20 x 20 mm in large, was closed directly. Her postoperative course was excellent with disappearance of cyanosis, normalized oxygen saturation in arterial blood and improved activity without dyspnea. PMID- 1758107 TI - [A case of surgical repair of aortic dissection associated with tear of the right coronary artery]. AB - A 39-year-old female with dissecting aortic aneurysm of DeBakey type I, underwent replacement of the ascending aorta. We found that the right coronary artery originated just distally from the left sinus of Valsalva, run transversally in the aortic wall. Because the entry of dissection occurred at the right coronary artery, it was torn longitudinally. Aorto (graft)-rt. coronary bypass grafting was performed. She had no ischemic heart symptoms postoperatively. It is supposed that the dissecting aortic aneurysm was caused by the anomalous origin of the right coronary artery. PMID- 1758108 TI - [Malfunction of the Omniscience valve in mitral position: a case report]. AB - A 55-year-old woman who underwent implantation of a 27 mm Omniscience valve in mitral position 5 and a half years ago, consulted our institution complaining reappearance of signs of mitral stenosis. In preoperative examinations, the maximal opening angle of the Omniscience valve was only 32 degrees and PCWP was elevated to 20 mmHg. Her symptoms disappeared after mitral valve re-replacement with a Medtronic Hall 27 mm prosthesis. The important point is that no foreign body such as thrombus or overgrown pannus interfering motion of the Omniscience valve was observed at the time of reoperation. The cause of insufficient opening seemed to be valve mechanism itself. PMID- 1758109 TI - [A case of cystic mediastinal lymphangioma]. AB - A 41-year-old man was admitted to our hospital because of an abnormal shadow which was pointed out on the chest x-ray film in mass screening. The operation was performed through left thoracotomy. The cyst was unilobular and 43 x 36 x 36 mm in size, located in the middle position of upper mediastinum. This localization has not been reported among 46 cases of the mediastinal lymphangiomas in Japan. Preoperative diagnosis is very difficult since roentogenographic feature is few for ruling out other mediastinal tumors. The complete resection of the cyst is recommended. PMID- 1758110 TI - [A case of an aberrant subclavian artery-esophageal fistula due to prolonged nasogastric intubation]. AB - A case of fatal hematemesis due to an aberrant right subclavian artery-esophageal fistula is presented. The patient was a 9-year-old male child with complex congenital heart disease and developed the fistula by prolonged tracheal and nasogastric intubation after Fontan type operation. To avoid this unusual but serious complication, aberrant subclavian artery should be treated surgically before repair of complex cardiac anomaly. PMID- 1758111 TI - [Methicillin-cephem-resistant Staphylococcus aureus (MRSA) mediastinitis following open heart surgery]. AB - Mediastinitis following cardiac surgery occurs frequently in association with high mortality and morbidity. Patient was a 6-year-old boy suffering from Sotos syndrome with secundum type of ASD. He was operated upon to repair ASD. Following the surgery, he suffered from MRSA mediastinitis and osteomyelitis of the sternum. Routine method of closed irrigation after reopening of the sternal wound was ineffective. Patient recovered following aggressive debridement repeatedly, open drainage and topical irrigation with vancomycin. This appears to be a useful method to treat MRSA mediastinitis of the sternum. PMID- 1758112 TI - [A successful correction of common atrium with left atrial isomerism]. AB - A successfully treated case of one-year-old girl of common atrium associated with bilateral superior vena cava and an interrupted inferior vena cava with hemiazygos continuation is reported. In addition to these anomalies of systemic venous connection, both atrial appendages show morphological characteristics of left type, and the final diagnosis of left atrial isomerism was made. In the corrective surgery, atrial septation was reconstructed using trimmed autogenous pericardial patch to allow the left superior vena cava to drain into the right side of the common atrium. The patient had been pointed out bradycardia (50 100/min) since her birth. Postoperative electrocardiogram also showed bradycardia (78-100/min). Especially in sleeping, her heart rate was 50-60/min, resulting in A-V junctional escaped rhythm and A-V dissociation. This fact suggests that her sinus node is absent or hypoplastic, one of the characteristics of left atrial isomerism. Since left atrial isomerism is reported to cause a decrease of atrial rhythm with aging, careful postoperative observation on specific arrhythmia is necessary. PMID- 1758113 TI - [A case report of surgical treatment of acute aortic dissection (DeBakey III B) in association with thoracic aortic aneurysm]. AB - This is a case report of 63-year-old man suffering from DeBakey III B acute dissection in association with thoracic aortic aneurysm. He had been following up for hypertension and thoracic aortic aneurysm. He was brought to the hospital by city ambulance complaining of sudden onset of severe back pain. Emergency operation was carried out. It revealed aneurysm of 90 mm in diameter located just distal to the aortic arch and an intimal tear or entry of the dissection located distal to the left subclavian artery. A low porosity Dacron graft was interposed between the distal aortic arch and middle portion of the thoracic descending aorta using inclusion technique. Systemic circulation was bypassing external iliac vein to artery using pump-oxygenator during aortic clamping. His postoperative course was uneventful. In review of the literature, association of the atherosclerotic aneurysm and acute dissection occurred approximately 5% in the cases of aortic dissection with increasing risk of aneurysmal rupture. PMID- 1758114 TI - [Serious complication of retrograde perfusion during repair of dissecting aneurysm: compression of the true lumen]. AB - Between 1982 and 1990, 61 patients underwent the repair of dissecting aneurysm. Retrograde perfusion from the unilateral femoral artery were performed for 56 patients and the selective false lumen perfusion occurred in 3 patients. As for those 3 patients, compression of the true lumen and insufficient cerebral perfusion were suspected. Selective cerebral perfusion and antegrade systemic perfusion from the ascending aortic graft were performed. Although 2 patients took uneventful postoperative courses, 1 patient died of massive brain damage. It is very important to accomplish the means to maintain adequate cerebral circulation as soon as possible toward this fetal complication. PMID- 1758115 TI - [Fontan type procedure in patient with borderline hemodynamics: using a temporary R-L shunt in early postoperative period]. AB - Fontan type procedure was successfully performed to a 14-year-old patient with borderline hemodynamics using a temporary R-L shunt in early post operative period. Preoperative diagnosis was DORV (ILD), small RV, PS, ASD, juxtaposition of atrial appendages and post bilateral B-T shunts. Preoperative catheterization studies showed low PARI but insufficient pulmonary arterial size (PA-index 220). In the Fontan procedure, RA was partitioned obliquely with a composite patch of xenograft and Dacron velour. A 5.5 mm hole was created only in xenograft to allow a temporary R-L shunt. During rewarming period, systemic pressure hovering around 60 mmHg with 10 micrograms/kg/min of dopamine and dobutamine. Then a R-L shunt was created by a side to side anastomosis between the appendages with the orifice diameter of 10 mm, followed by a rise in the systemic pressure up to about 80 mmHg. One post operative day, a readjustable occluder was applied at the site of appendage anastomosis to control R-L shunt flow. According as CVP decreased, the occluder was tightened up step by step. Finally, the occluder was fully tightened up in 10 post operative days. This experience suggests that a temporary R-L shunt in early post operative period may be applicable in patient with borderline hemodynamics for Fontan type procedure. PMID- 1758116 TI - [Surgical repair of ischemic mitral regurgitation]. AB - We studied surgical results of 14 cases of ischemic mitral regurgitation. There was no surgical death in 10 cases with left ventricular aneurysm, and their clinical symptoms improved except 3 with the combined operation of left ventricular aneurysmectomy, mitral annuloplasty and bypass grafting. The range of the abnormal contracting segment significantly decreased after surgery except in 3 cases in whom clinical status was not improved. Three of 4 cases which underwent bypass grafting and mitral annulo-valvuloplasty survived, but one of them died of graft-versus-host disease. In the three survived cases, severe mitral regurgitation disappeared. We have concluded as follows: In cases of left ventricular aneurysm, a sufficient aneurysmal resection is very important to control the mitral regurgitation, and the additional procedures of mitral annuloplasty and bypass grafting are essential. The mitral valve replacement is recommended in case of the complete disruption of the papillary muscle. Mitral valvuloplasty combined with annuloplasty is suitable to control the regurgitation in the regional mitral prolapse due to the torn chordae. PMID- 1758117 TI - [Etiology of left ventricular rupture following mitral valve replacement]. AB - Two uncommon cases of left ventricular rupture that occurred during cardiac surgery were treated successfully. These cases may be useful in understanding the etiology of common left ventricular rupture following mitral valve replacement. One case occurred during coronary bypass surgery. The myocardium which is already abnormal seems to be weak to trauma such as bending, traction and torsion. In the other case, who underwent mitral valve replacement with preservation of the posterior leaflet with its attached chordae, the disruption was localized in the epicardial side of the left ventricular posterior wall, though direct injury by some instrument was excluded as a possibility, with a depth of half the thickness of the wall. In experiments using dogs, shape and movement of the mitral annulus were examined. The length of the annulus attached to the posterior leaflet in end systole was shortened to 89.0 +/- 4.6% of that in late diastole. Furthermore, the annulus was distorted by the elevation of the heart. We approve of Cobbs' "untethered ventricle theory" and consider moreover as follows: In general, whether with or without preservation of the mitral loop, the mitral annulus and the left ventricular posterior wall after mitral valve replacement are severely constricted by the rigid prosthetic ring and become tense, which limits movement in both circular and longitudinal directions. Then even slight stress may cause a primary tear on the posterior wall of the left ventricle, resulting in rupture. In order to treat the rift, the prosthesis must be removed before the apex of the heart is lifted, to avoid excessive ventricular wall tension. PMID- 1758118 TI - [Recommendation for open heart surgery in infancy]. AB - Progress in infant open-heart surgery last 10 years was reviewed mainly based on the surgical experiences in Fukuoka Children's Hospital. Recent advances and present problems in patient's care, cardiopulmonary bypass methods and cardioplegia were discussed. Low surgical mortality of 4.8% in 245 infant open heart repairs between 1988 and 1990 in Fukuoka is highly suggestive of early primary repair for most of congenital heart diseases. PMID- 1758119 TI - [Current problems in valvular surgery]. AB - Based upon our experiences of 661 valvular operations for these 10 years, we discussed about three major topics in valvular surgery. The first is the current status of valve repair versus replacement. The second is on the changing aspects of patients undergoing valvular surgery. Finally difficult problems in the treatment of infective endocarditis was discussed. PMID- 1758120 TI - [Surgical treatment of coronary artery disease]. AB - The indication in revascularization surgery is quite complicated, as the manifestation of the anatomical disease in the major three coronary arterial trees are innumerable and different as the face of each patient. Even though it is simply grouped into three categories as single, double and triple vessel disease, the combination of the degree and position of the obstructive lesions and the status of left ventricular function is varied in each instance. Adding further the patient's specific variables and risk factors to the anatomical variance, the situation becomes more complex. During the first decade of revascularization surgery, several large scale clinical studies were carried out in the United States and Europe to define the subsets of patients who were more benefited by revascularization surgery than medical treatment. The technique of aorto-coronary bypass graft (CABG) surgery also rapidly developed during this period and more complete revascularization using more durable conduits such as the internal mammary artery grafts with less surgical morbidity and mortality has been attained in the second decade. The appearance of PTCA (percutaneous transluminal coronary angioplasty) as a new invasive modality of treatment by the cardiologist towards the end of 1970's further complicated the indication of CABG. The comparative benefit of PTCA & CABG should be searched by the objective prospective randomized studies but such studies may be very difficult to be conducted in large scale, and meantime the number of PTCA will continue to increase. Based on the ACC/AHA Task Force Report, "Guideline and Indication for Coronary Artery Bypass Graft Surgery.": JACC Vol. 17, No. 3 March 1, 1991: 543 89, some of the subjects in surgical treatment of coronary artery disease were discussed in this paper. PMID- 1758121 TI - [Myocardial protection: some problems and recent progress]. AB - One of the great advances in cardiac surgery in the past 20 years has been the concept of myocardial protection "cardioplegia". But even now, there are some controversies about the methods for myocardial protection. In this review, controversy between crystalloid and blood cardioplegia, between extracellular and intracellular cardioplegic solution are discussed. And then the recent advances in cardioplegia, terminal warm blood cardioplegia, retrograde infusion of cardioplegic solution and cardioplegia in infants are reviewed. PMID- 1758122 TI - [Recent advancement of surgical treatment of aneurysms of the thoracic aorta]. AB - The recent advancement of surgical treatment for aneurysms of the thoracic aorta with special reference to the operative technique and adjunctive methods of distal aortic perfusion during aortic cross-clamping were reviewed. Between 1960 and July, 1991, 415 patients underwent operation for aneurysms of the thoracic aorta in our institution. The overall early mortality rates were 7.7% for the nonruptured aneurysms and 30.6% for the ruptured aneurysms during the last 10 years with recent establishment of mechanical adjuncts and refinement of operative technique. Composite graft replacement with coronary reimplantation was employed in the treatment of annuloaortic ectasia. Selective cerebral perfusion (SCP) with an open aortic anastomosis is a useful adjunct in the treatment for aneurysms of the aortic arch. Graft inclusion technique (Crawford's method) with the aid of a partial bypass is a valid technique for the treatment of thoracoabdominal aortic aneurysms involving visceral branches. Emergency operation is necessary for acute type A aortic dissection to prevent the sudden death due to cardiac tamponade. Acute aortic arch dissection can be treated surgically by replacing both the ascending aorta and aortic arch with prosthetic graft using SCP and open aortic anastomosis. Because of poor prognosis of the aneurysms of the thoracic aorta, and improvement in present surgical results, it now seems justifiable to support an aggressive surgical approach to this disease, before the fatal rupture occurred. PMID- 1758123 TI - [Recent surgical treatment of thoracic esophageal carcinoma]. AB - Nowadays, surgery for a thoracic esophageal carcinoma is accomplished safely, however, there still remain many problems concerning curative resection. Cancerous recurrences of the lymph node is still high against to lymph node dissection around thoracoabdominal region. Therefore, surgery should endeavour to prevent such lymphatic recurrences. In the patients with a carcinoma in the upper or middle third of the esophagus, who underwent extended radical esophagectomy, a significantly high incidence of metastasis in the recurrent nerve lymphatic chain was noted in comparison with that in patients with that in those who underwent standard radical resection. Complete resection of the recurrent nerve lymphatic chain is generally difficult through the thoracic approach alone, and such approach might be the factor causing the poor prognosis after standard radical surgery for an upper or middle thoracic esophageal carcinoma. Accordingly, extended radical surgery by the cervicothoracoabdominal approach can produced improved surgical curability for an upper or middle thoracic esophageal carcinoma. On the other hand, pulmonary complications are still a major postoperative complication following radical esophagectomy due to extended radical lymphadenectomy around the paratracheobronchial region. So, it is now clear that we should preserve the right bronchial artery and pulmonary nerves branched from the vagus nerve during the thoracic procedure, if these unaffected by cancerous invasion. Adopting this procedure resulted in a marked decrease in the incidence rate of postoperative severe pulmonary complications. Finally, in the near future we expect to develop criteria to select the best treatment for each specific individual based on preoperative studies of the biological characteristics of the carcinoma. PMID- 1758124 TI - [Postoperative complications and treatments after Bentall operation]. AB - Postoperative complications of Bentall operation for the annuloaortic ectasia have frequently occurred, although the mortality has been reduced. To reduce complications after Bentall operation we have taken three major treatments since 1987. The first was reimplantation technique of coronary ostia in replacing the ascending aorta and the aortic valve with a tube graft. The second was the infusion technique of cardioplegic solution such as retrograde cardioplegia infusion. The third method was to save blood and reduce the blood transfusion by preserving autoblood preoperatively and using cell saving machine. The purpose of this study was to analyse 20 patients who underwent the Bentall procedure and to investigate the effect of our treatments in Bentall operation on the operative results. We divided our patients into two groups. Fourteen patients in the group 1 were operated before 1987, when our principles were not performed. Six patients in group II were operated under the principles mentioned above. There were no differences in cardiopulmonary bypass time and ischemic time between group I and II. Transfused blood volume in group II was remarkably less than that of group I. Postoperative complications occurred in all patients in group I (100%), while three patients in group II (50%) had complications (p less than 0.05). We, hence, conclude that our method could be useful for reducing postoperative complication rate in Bentall operation. PMID- 1758125 TI - [Experience of predeposit autologous blood transfusion and medication of recombinant human erythropoietin in pediatric open heart surgery]. AB - To avoid using the homologous blood, 11 children between the age of 5 and 15 years donated autologous blood of 10 ml/kg of body weight (upper limit 400 ml) once a week for two weeks prior to elective open heart surgery. Five of 11 children received erythropoietin (100 U/kg of body weight) intravenously three times a week for two weeks. Only one patient experienced a mild donor reaction but no adverse effects occurred in erythropoietin therapy. In all the patients cardiac operations were able to be completed without homologous blood transfusion. Patients treated with erythropoietin were not anemic despite of preoperative donation although without erythropoietin therapy patients were mildly anemic. Our experience documents safety and effectiveness of predeposit autologous blood transfusion and erythropoietin therapy in pediatrics. PMID- 1758126 TI - [A case of cardiac lipoma in the ventricular septum]. AB - A 45-year-old man was admitted because of systolic murmur after routine medical checking. Echocardiography and cardiac catheterization revealed a large mass in the ventricular septum which bulged into right ventricular cavity with pressure gradient of 29 mmHg. The diagnosis of cardiac lipoma was made by CT scanning which showed the mass with attenuation values of -94 Hounsfield units. MR imaging demonstrated the mass with high signal intensity which corresponded to that of subcutaneous fatty tissue. The tumor was resected through the right ventricular incision with the use of cardiopulmonary bypass. It was yellow, elastic soft, sized 6.5 x 4.3 x 3.5 cm, and weighed 44.7 g. On histological examination, the tumor was composed of mature fatty tissues contained with myocardial fibers. After operation, he had split of the ventricular septum, which was closed primarily after removal of the lipoma, and left-to-right shunt. Patch reinforcement was performed at the right ventricular side of the septum on the postoperative 18th day. Postoperative electrocardiogram showed left axis deviation and complete right bundle branch block. This finding seems to be resulted from injury to the anterior branch of left bundle. The postoperative course was uneventful. This patient is the second case of removal of cardiac lipoma in the ventricular septum on review of the literature in Japan. PMID- 1758127 TI - [Successful repair of TGA with ventricular septal defect, the outflow tract stenosis of the left ventricle and coarctation of the aortic arch]. AB - A 9-month-old boy after the coarctectomy at 5 months old was successfully repaired by Senning procedure with closure of ventricular septal defect and resection of the membranous septal aneurysm causing the outflow tract stenosis of the left ventricle. Retrospectively, this case might have been possible to do Jatene procedure, however, attempts to resect the left ventricular outflow tract stenosis often failed to relieve stenosis completely. Therefore, the intraatrial switch operation seems to be better than the arterial switch operation when there is a possibility to remain left ventricular outflow tract stenosis. True estimation for these cases must await more case studies. PMID- 1758128 TI - Great expectations. PMID- 1758129 TI - With privilege comes responsibility. PMID- 1758130 TI - Peer review revisited. PMID- 1758131 TI - The EACH concept. Part II: A physician's perspective. PMID- 1758132 TI - Ventricular tachycardia in a newborn of a mother with scleroderma. PMID- 1758133 TI - Physician to rancher (and back again). Part Three. PMID- 1758134 TI - Managing survivors of ventricular fibrillation. PMID- 1758135 TI - [Therapy of acute myeloid leukemia in children--results of the AML II/87 multicenter study]. AB - Fifty seven patients entered the cooperative study AML II/87 of the working group "Pediatric Hematology and Oncology" of East Germany. Two patients with initial hyperleukocytosis died prior therapy. 13 patients died within the first 4 weeks of therapy, 3 patients did not respond to therapy, and one patient is not yet in remission. 38 patients (70%) attained a complete remission. 15 patients get a bone marrow transplantation in first CR (10 autologous BMT without purging, 5 allogenous BMT). 12 of them are living and well 3 to 34 months after BMT. 9 of the 23 patients under chemotherapy relapsed, one patient is lost to follow up. 13 patients are living in continuous complete remission. The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival (DFS) and 0.60 for event free interval (EFI). The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI. PMID- 1758136 TI - [Course and prognosis of internal hydrocephalus in children]. AB - Sixty-two patients with infantile hydrocephalus were reexamined at ages ranging from 2-19 years. Operations had been performed in 46 children. The long-term intellectual prognosis of hydrocephalus is described. Sex, age and frequency of shunt complications are not related to intelligence level. In general, hydrocephalus due to spina bifida and aquaeduct stenosis results in a better intelligence level than hydrocephalus to other reasons. PMID- 1758137 TI - [Long-range intelligence development of children with congenital hypothyroidism]. AB - The intellectual development of 105 children with congenital hypothyroidism was assessed. In 70 children the assessment was repeated in several times. Correlations between development of intelligence and influence of biological and/or psychosocial risks were verified. PMID- 1758138 TI - [Modification of anxiety in children prior to dental treatment using premedication with Faustan diazepam)]. AB - In about 22% of children aged from 7 1/2 to 12 years we established heavy reaction of anxiety. To proof the influence of Diazepam to dental treatment we carried out clinical investigations in 40 patients. By means of premedication with Diazepam we got a positive effect for readiness of treatment. PMID- 1758139 TI - [Development of body weight and height of small-for-gestational-age infants in relation to the degree of intrauterine retardation]. AB - The increase of weight of 238 hypotrophic and 31 eutrophic newborns is analyzed and assigned to 4 clusters in the course of their first 21 months. It is compared with body weight curves by Prader. Cluster 1 Increase in weight about the 50th percentile Cluster 2 Increase in weight between the 50th and 3rd percentile Cluster 3 Increase in weight just below the 3rd percentile Cluster 4 Increase in weight clearly below the 3rd percentile More than a half of all hypotrophic newborns had a body weight below the 3rd percentile by Prader (cluster 3 and 4) on attaining the age of 21 months. The appearance of hypotrophy in the newborns is subdivided into 4 groups by means of gestational age and relative birthweight: Group 1 eutrophic and moderate hypotrophic (n = 77) Group 2 premature and moderate hypotrophic (n = 46) Group 3 eutrophic and distinct hypotrophic (n = 62) Group 4 premature and distinct hypotrophic (n = 53) We found that the increase of weight correspond to cluster 4 in 4% of group 1, in 22% of group 2, in 32% of group 3, and in 43% of group 4. At last the increase of body weight is hard influenced in the first 3 years of life by hypotrophy and degrees of maturity of the newborns. PMID- 1758140 TI - [Opitz' trigonocephaly syndrome]. AB - The Opitz' Trigonocephaly Syndrome, also called C-syndrome is an important autosomal recessive inherited disorder with characteristic synostosis of metopic suture, craniofacial abnormalities and severe mental retardation. Some patients show chromosomal aberrations with the possibility of prenatal diagnosis. Are reported on three children from two families with typical dysmorphic stigmata of the syndrome. PMID- 1758141 TI - [Pfeifer type acrocephalosyndactylia (McK 10160, 18075)]. PMID- 1758142 TI - [Rental contracts in medical practice--what should be considered?]. PMID- 1758143 TI - [Valproate-associated hepatotoxicity--pathogenesis, clinical aspects, therapy and prevention]. AB - The potential hepatotoxicity resulting in fatal liver failure is of major concern in treating patients with valproate (VPA). Until now there is no relevant laboratory parameter allowing early detection of impending liver failure. The major routes of VPA biotransformation are glucuronidation and beta-oxidation. There are several other pathways of degradation with formation of mono- und di unsaturated derivates. VPA dose, patients age, co-medication (anticonvulsants, aspirin), fasting and glucose supply influence the VPA metabolism. The clinical spectrum of VPA-associated hepatotoxicity reaches from slight increases of liver enzymes without clinical manifestations over reversible slight to severe liver dysfunction to fatal liver failure. With respect to pathogenesis attention has focused on depletion of beta-oxidation and change of biotransformation to other pathways with increased synthesis of toxic unsaturated VPA derivates. Several inborn errors of metabolism, acute infections and status epilepticus seem to predispose to liver failure. Another hypothesis lies in the possible VPA-induced depression of free radical scavenging enzyme activities. On this basis N acetylcysteine has been used successfully in treating children with severe hepatotoxicity. In the presence of certain risk factors VPA should be avoided. PMID- 1758144 TI - [Treatment of obstruction and thrombosis due to central venous catheterization]. AB - Thrombolytic treatment with urokinase (5000 U/ml) or streptokinase can restore patency in central venous catheters occluded by thrombosis. In pediatric patients preferable urokinase should be used. The therapy in case of catheter-induced central venous thrombosis is a continuous urokinase infusion (125,000 U/1.73(2)/h) for about 3 to 8 days, followed by a long-term heparinization. The treatment in persistent withdrawal occlusion is significantly shorter, a few hours of systemic lysis are sufficient. The treatment of choice in case of chemical obstructions in patients with long-term parenteral nutrition is the injection of 0.1 N HCl in combination with Heparin. By these procedures most of obstructed central venous catheters can be reopened and maintained in place. This preserves the count of possible catheter implantation sites. PMID- 1758145 TI - [Hemostatic changes in idiopathic venous thrombosis in childhood and adolescence]. AB - The prevalence of inherited thrombotic syndrome in the general population appears to be higher than that of inherited bleeding disorders. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40 years: In 18 children and adolescents suffering from "idiopathic" vein thrombosis laboratory screening has been performed: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1 antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2 macroglobulin. Compared to an age matched healthy control group in children with idiopathic vein thrombosis we could demonstrate in vitro platelet activation with significant enhanced platelet aggregation and elevated levels of von Willebrand factor in the onset of the disease. Antithrombin III, protein C, alpha-2 antiplasmin and alpha-2-macroglobulin were significantly decreased. These changes turned to be normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and c1-inactivator showed no alterations compared to the control. Platelet activation and alteration of platelet function in vivo and in vitro is established to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The decreased inhibitors of the hemostatic system antithrombin III and protein C in the onset period of thrombotic diseases are discussed to be an increased turnover, whereas the decreased levels of alpha-2-antiplasmin and alpha-2-macroglobulin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system. PMID- 1758146 TI - [Epidemiology of infectious diseases in children in the old states of the Federal Republic of Germany]. AB - This study was done to describe the epidemiology of infectious diseases in children living in the old countries of the Federal Republic of Germany. After an intensive search for literature, data about notifiable diseases, data from insurance agencies and a random test from 700 charts of a general pediatrician were reviewed and analysed in a standardized way for their validity. No single review article on this topic was found. Estimates about the frequency of some specific infectious diseases as well as data about notifiable diseases proved to be unreliable and not useful from a scientific point of view. Published insurance data suggested, that infectious diseases may contribute comparatively little to the morbidity of the population. In contrast, chart analysis revealed that every second visit at a pediatrician's office was prompted by an infectious disease. It is concluded, that there are only insufficient and unreliable data about the epidemiology of infectious diseases in children in the western part of the FRG and that this unsatisfying situation could be changed by using the technique of representative evaluation. PMID- 1758147 TI - [Gelastic epilepsy and precocious puberty in hamartoma of the hypothalamus]. AB - Four cases of hypothalamic hamartoma leading to gelastic epilepsy, precocious puberty and behavioural disorders are reported. Cerebral neuroradiologic examinations revealed a tumor-like mass attached to the hypothalamus in the region of the mamillary bodies in all cases. Precocious puberty developed in the two girls at 4 and 13 months but in neither of the two boys, who both suffered behaviour disturbances in the form of aggressive outbursts. A total resection of the tumors of both boys led to histologic confirmation of hamartoma. One boy was free of seizures upon follow-up, whereas seizure frequency in the other boy was reduced, while his aggressivity increased. The cases are discussed in context of current therapeutic conceptions of gelastic epilepsy and central precocious puberty. PMID- 1758148 TI - [Diagnosis of coxitis fugax, the most frequent hip disease in childhood]. AB - After a review of the history, clinical features, laboratory findings, imaging techniques and the treatment of coxitis fugax, the authors inform about 131 own cases. In this disease of the hip joint, which is most commonly encountered in childhood, differential diagnosis is of the utmost importance. In the present study, the initial diagnosis had to be changed in eleven cases affected with this condition, which is also referred to as "observation hip". The patients ultimately contracted severe diseases such as leukaemia, juvenile polyarthritis or Perthes' disease. PMID- 1758149 TI - [Comparative determination of microalbuminuria using radioimmunoassay and kinetic nephelometry in children and adolescent with and without Type-I diabetes mellitus (IDDM)]. AB - In 73 healthy (group I) and 32 children and juveniles with insulin dependent diabetes mellitus (IDDM, group II) urinary albumin excretion is determined by radioimmunoassay (RIA) and kinetic nephelometry. Intention of the study is to examine, if the kinetic nephelometry is--as observed in adults--a suitable method also in children and juveniles to detect microalbuminuria (greater than 30 mg/d). In both groups albumin excretion is observed in every urine sample when measured by RIA. Because of it's higher threshold kinetic nephelometry detects albumin excretion only in a part of the urine samples. The correlation between the two methods is very high (r = 0.905, p less than 0.001, n = 174). So kinetic nephelometry is not suitable to determine reference values. But as a faster and possibly more specific method than RIA nephelometry is a very effective way for a screening of microalbuminuria also in children and juveniles. PMID- 1758150 TI - [Neonatal form of a nonketotic hyperglycinemia in consanguinous parents]. AB - This is a report of the neonatal form of nonketotic hyperglycinemia with rapid progressing neurological symptoms, respiratory distress and seizures. The EEG pattern is characteristic, the ratio of cerebrospinal fluid to plasma glycine abnormally high. The result of cranial computerized tomography demonstrates also in our patient that nonketotic hyperglycinemia joins a growing list of inborn errors of metabolism associated with brain malformations. The consanguinity of parents supports the known autosomal recessive form of inheritance. PMID- 1758151 TI - [Familial Mediterranean fever]. AB - Familial Mediterranean Fever is a genetically determined disease occurring predominantly in Arabs, Armenians, Jews and very rarely in Turks. It is characterized by moderately elevated body temperature and by abdominal, pulmonary or arthritic complaints. These symptoms are recurrent appearing at short intervals and persisting for not more than two days. Renal amyloidosis may be a complication. Thus, treatment should be continued for life. The pathomechanism of the disease is not clear. Colchicine has been shown to give good symptomatic relief. Surprisingly, the prolonged use of this mitotic poison is virtually devoid of untoward side effects, even in pregnancy and childhood. PMID- 1758152 TI - [Adrenocortical nodular hyperplasia as a cause of Cushing syndrome in the neonatal period]. AB - The case report of a female child born preterm (30th wk of gestation) who developed symptoms of Cushing's syndrome beginning in the neonatal phase is presented. The disease was caused by a unilateral adreno-cortical nodular hyperplasia and was successfully treated by unilateral adrenalectomy. Preoperative treatment with ketoconazole and metyrapone proved to be effective. Symptoms of Cushing's disease including hypertrophic cardiomyopathy were completely reversible within one month after surgery. PMID- 1758153 TI - [Employment situation in Swiss hospitals. Personnel shortage is decreasing]. PMID- 1758154 TI - [When children cannot sleep]. PMID- 1758155 TI - [From swaddling clothes to disposable diapers]. PMID- 1758156 TI - [Pathways out of the torture chamber]. PMID- 1758157 TI - ["There is no escape--not for one second". Interview by Martin Glauert]. PMID- 1758158 TI - [Strategy of the European Council--and what the Swiss Nursing Society is already doing]. PMID- 1758159 TI - [A meaningful task for a nurse]. PMID- 1758160 TI - [A challenge to civilization: the accumulating trash]. PMID- 1758161 TI - [Experiences of the Fribourg Hospital]. PMID- 1758162 TI - [Patient controlled analgesia: a useful instrument]. PMID- 1758163 TI - [The relational dimension in public health]. PMID- 1758164 TI - [Towards recognition of the nursing effort. 2]. PMID- 1758165 TI - [Higher studies in nursing: a new university program]. PMID- 1758166 TI - [Behind the technique there is always a person]. PMID- 1758167 TI - [What does the Swiss Nursing Association offer you?]. PMID- 1758168 TI - Oxygen radicals alter LDL permeability and uptake by an endothelial-smooth muscle cell bilayer. AB - There is evidence to suggest that the deposition of lipid within the arterial wall, which is characteristic of atherosclerosis, involves a break in the integrity of the endothelial barrier. Oxidative modification of low density lipoproteins by reactive oxygen species may enhance this process. In this study, an aortic endothelial (EC) smooth muscle cell (SMC) bilayer was briefly exposed to a free-radical generating system to determine the effect of superoxides on lipid permeability and uptake. 125I-LDL (10 micrograms/ml) was added to the EC medium at various time intervals (3, 24, and 48 hr and 9 days). The amount of lipid reaching the subendothelial space was measured. Measurements of EC and SMC binding and uptake of LDL were also obtained and compared with those of untreated cells. The results demonstrate a significant increase in the permeability of the treated EC layer to LDL (P less than 10(-6)), which was sustained over time. Superoxide exposure led to a limited initial increase in EC binding and uptake of LDL, which later returned to control values. In contrast, SMC uptake of LDL was significantly (P less than 10(-3)) and persistently increased over control values and disproportionately increased over cellular binding. Such results suggest that superoxides can increase LDL permeability of the EC barrier. Because this was not associated with a comparable increase in EC binding and uptake, it is unlikely to be due to changes in receptor-mediated, transcellular transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758169 TI - Stress-induced gastric lesions and the synthesis of prostaglandins and leukotrienes. AB - Prostaglandin E2 renders the mucosa of the GI tract more resistant to acute injury by aspirin, acid, bile salts, and stress, whereas leukotrienes promote inflammation and retard healing of ulcers. The relationship of stress ulcer formation to changes in the activities of prostaglandin synthetase and lipoxygenase was evaluated in this study. After a 24 hr fast, 10 rats were stressed by the cold-restraint method for 4 hr and 10 rats were not stressed. Rats were terminated, stomachs were excised, the number of lesions were counted, and the nonulcerated mucosa was assayed for prostaglandin E2 and leukotriene synthesis. The mucosa was minced, washed in buffered saline, and then incubated for 10 min in a 1.3 mM sodium arachidonate solution containing a nonionic detergent (poloxamer 188), NaCl, KCl, KPO4, glutathione, hemin, MgSO4 and Hepes at pH 8.0. An ANOVA was used to compare the groups. Following stress the number of gastric lesions increased from 0.7 +/- 0.6 to 13.5 +/- 2.6, while leukotriene synthesis increased from 173 +/- 20 to 2170 +/- 187 pg/mg/min. A shift in synthesis from prostaglandins to leukotrienes in the mucosa appears to be detrimental to cytoprotection. PMID- 1758170 TI - Cross-species bone marrow transplantation: evidence for recognition of skin specific antigens across a species barrier (rat----mouse). AB - We have developed a model to study cross-species bone marrow transplantation and the associated donor-specific transplantation tolerance induced using fully xenogeneic chimeras. Reconstitution of lethally irradiated B10 mice with untreated F344 rat bone marrow cells results in fully xenogeneic chimerism (F344 rat----B10 mouse). Survival of recipients is excellent (greater than 80% at 100 days) and stable rat lymphoid and multilineage chimerism are present throughout the life of the chimeras. Recipients are specifically tolerant to donor-type skin xenografts yet are competent to reject major histocompatibility complex (MHC)- disparate third party strain rat xenografts. Although prolonged, donor-specific skin xenografts underwent chronic rejection which had its onset at approximately 40 days following skin graft placement. We have now examined these chimeras by serial flow cytometry typing to determine whether this is due to skin-specific antigens expressed on skin, but not on the bone marrow elements to which the chimeras were rendered tolerant. In all animals examined, lymphopoietic chimerism persisted unchanged even after the onset of inflammation in the grafts, suggesting the presence of skin specific antigens. This model may provide a method to study tissue and organ specific antigens recognized across a species barrier. PMID- 1758171 TI - A case-control comparison of durability and cost between implanted reservoir and percutaneous catheters in cancer patients. AB - A case-control study was performed to compare the durability and cost of implanted reservoir catheter systems with percutaneous central venous catheters. Twenty cancer patients had reservoir systems placed in 1985 for chemotherapy delivery. The control group consisted of 60 cancer patients, matched according to age, sex, and diagnosis who were part of a group of more than 700 patients with percutaneous catheters inserted during the same period. The reservoir catheters were found to function for a significantly (P less than 0.0001) longer time (495 +/- 54 days) compared to the percutaneous catheters (197 +/- 22 days). The total cost for each system was calculated by adding the charges for an average insertion (reservoir = $1738, percutaneous = $562) to the maintenance charges accumulated over the catheters' lifespan. Reservoir catheters were associated with a significantly greater total cost than percutaneous catheters ($2233 +/- 54, $1453 +/- 102, respectively) but, if the total cost was spread out over the lifespan of the catheter by dividing the total cost by duration of use, reservoir catheters can be less expensive on a per diem basis. The break point occurs at approximately 6 months. For use less than 6 months, percutaneous catheters are cheaper primarily because of their lower insertion costs, but, for longer periods, reservoir catheters become cheaper because of lower maintenance costs and because a second percutaneous catheterization would likely be necessary. PMID- 1758172 TI - Reduction of experimental neuroma formation with ricin. AB - Twenty rat sciatic nerves were bilaterally transected, one as control, and one intraneurally injected with ricin. At 11 weeks, all controls demonstrated large neuromas. Ten injected nerves had no neuroma or a significantly smaller one, while the other 10 had neuroma formation similar to controls. No effect on distant dorsal root ganglia or spinal cord was seen. Thirteen additional rats underwent nerve injection with I125-labeled ricin. At one week, most radioactivity was localized to sciatic nerve, surrounding muscle, and thyroid, with trace amounts in dorsal root ganglia and spinal cord. Intraneural ricin can inhibit neuroma formation in transected nerve, but results in unpredictable uptake of ricin by nerve and excess spillage into surrounding tissues. PMID- 1758173 TI - Perfusion parameters and pressure at zero flow in canine gracilis muscle flaps. AB - The perfusion parameters and pressure at zero flow were examined in island gracilis muscle flaps in dogs under sodium pentobarbital anesthesia. Complete surgical isolation of the muscle preparation was obtained. Normal blood flow in denervated muscle in situ was 8.0 +/- 0.8 ml/min/100 g tissue as measured by electromagnetic blood flowmetry. The artery supplying each flap was occluded with a microclip and the drop in pressure distal to the clip was observed. The lowest pressure obtained following occlusion was the pressure at zero flow. A positive pressure at zero flow in the vascular bed was thereby identified at a pressure of 10.3 +/- 1.2 mm Hg. PMID- 1758174 TI - Chylomicrons can inhibit endotoxin activity in vitro. AB - Trauma, thermal injury, and nonlethal doses of endotoxin can promote the translocation of endotoxin across the mucosal barrier of the colon into the mesenteric lymphatics and systemic circulation. Bacterial endotoxemia induces changes in lipid metabolism, including an increase in circulating triglyceride rich lipoproteins. Because cholesterol-rich lipoproteins can neutralize the toxic activity of endotoxin, both in vitro and in vivo, we asked whether triglyceride rich chylomicrons can inhibit endotoxin activity in vitro as measured by a chromogenic Limulus assay. We tested the effect of intact versus heat-denatured chylomicrons on the in vitro activity of increasing concentrations of Escherichia coli (055:B5) endotoxin. Intact chylomicrons inhibited up to 12-fold the detection of as much as 1 microgram of endotoxin/mg of chylomicron triglyceride, compared to denatured chylomicrons (P less than 0.001). This study shows that chylomicrons are potent inhibitors of endotoxin activity in vitro. Because translocated endotoxin from the colon associates with gut-derived chylomicrons in the mesenteric lymphatics, this may represent a natural defensive mechanism against endotoxemia of enteric origin. PMID- 1758175 TI - Fluid percussion barotrauma chamber: a new in vitro model for traumatic brain injury. AB - Advances in the understanding of the pathophysiology of traumatic brain injury have implicated a number of cellular events as fundamental to the evolution of neurologic dysfunction in this process. Following the primary biomechanical insult, a highly complex series of biochemical changes occur, some of which are reversible. The development of fluid percussion injury as an in vivo model for traumatic brain injury has greatly improved our ability to study this disease. However, a comparable in vitro model of biomechanical injury which would enable investigators to study the response to injury in isolated cell types has not been described. We have developed a model of transient barotrauma in cell culture to examine the effects of this form of injury on cell metabolism. This model employs the same fluid percussion device commonly used in in vivo brain injury studies. The effect of this injury was evaluated in monolayers of human glial cells. Cell viability by trypan blue exclusion and the production of leukotrienes following increasing barotrauma was investigated. This model provided a reproducible method of subjecting cells in culture to forces similar to those currently used in animal experimental head injury. PMID- 1758176 TI - Low oxygen delivery produced by anemia, hypoxia, and low cardiac output. AB - In pentobarbital-anesthetized dogs, oxygen delivery (DO2) was measured by thermodilution cardiac output and cooximeter determined oxygen content, while oxygen consumption (VO2) was measured independently by spirometry. Oxygen delivery was decreased by isovolemic dilutional anemia, breathing hypoxic gas mixtures, or cardiac tamponade to reduce cardiac output. Baseline VO2 (cc/kg/min) for the three groups was 5.9 +/- 0.7 (anemia), 5.4 +/- 0.4 (hypoxia), and 5.6 +/- 0.1 (low C.O.) (NS). A critical level of oxygen delivery (DO2crit) was found at 9 10 cc/kg/min (anemia), 10-11 cc/kg/min (hypoxia), and 9-10 cc/kg/min (low C.O.) (NS.). Below this level, VO2 fell (became supply dependent) and lactic acidosis occurred, regardless of the mechanism of impaired oxygen delivery. PMID- 1758177 TI - Ventricular septal defect caused by nonpenetrating trauma in a 3-year-old child: use of extracorporeal membrane oxygenation in preoperative stabilization. PMID- 1758178 TI - A case of hives and hip pain following steroid injection. PMID- 1758179 TI - Endobronchial tuberculosis mimicking lung cancer. PMID- 1758180 TI - Radiology case of the month. Carbon monoxide poisoning. PMID- 1758181 TI - OBRA 1987 and the role of the physician in long-term care. PMID- 1758182 TI - Safety belts. PMID- 1758183 TI - Advertising and alcohol sales: a legal impact study. AB - According to the single distribution theory increases in the availability of alcoholic beverages in the general population are associated with increases in average consumption and increases in alcohol-related damage. If it can be demonstrated that advertising contributes to availability, perhaps in the form of what has been called social or subjective availability, then advertising could be considered an appropriate target of prevention. A 58-year ban on advertising of alcoholic beverages was lifted in Saskatchewan in 1983. Data on monthly sales of beer, wine and distilled spirits were examined for the years 1981 to 1987. Box Jenkins time series techniques were used to estimate the statistical relationship between the policy change and volume of sales of alcoholic beverages. The results revealed that sales of beer increased and sales of spirits decreased following the change in legislation that permitted alcohol advertising in Saskatchewan. The main finding is that there was no impact on wine and total alcohol sales from the introduction of alcohol advertising. Alcohol advertising may have produced a substitution effect with respect to beer and spirits, but this was not predicted. This evaluation suggests that alcohol advertising is not a contributory force that influences the overall level of alcohol consumption. The place of advertising in the single distribution theory remains not proven, and the place of advertising as an instrument of public policy with respect to the prevention of alcohol-related damage remains in question. PMID- 1758184 TI - Program integrity as a moderator of prevention program effectiveness: results for fifth-grade students in the adolescent alcohol prevention trial. AB - This study reports the results of a test of the quality of program delivery (program integrity) as a variable that may moderate the effectiveness of alcohol prevention programs. Two theory-based programs, Resistance Training and Normative Education, were delivered to fifth-grade students who were then tested on program relevant mediating variables. Resistance Training was found to improve students' knowledge of peer pressure resistance strategies, their performance on a behavioral assessment of peer pressure resistance skills and the manifestation of their future intentions to drink alcohol. Normative Education was found to improve students' perceptions of a conservative norm regarding alcohol use, facilitated their belief that refusing unwanted offers to drink alcohol could be easily accomplished and reduced their perceptions of the prevalence of alcohol use. Program integrity was measured by program specialists who taught the programs to students and by trained observers. Ratings of program integrity were found to significantly moderate outcomes for three of seven mediating variables. Affected were knowledge of peer pressure resistance strategies, behavioral pressure resistance skills and perceived self-efficacy. These results suggest that the quality of program delivery and reception may play an important moderating function on prevention program effectiveness. PMID- 1758185 TI - Biases in the perception of drinking norms among college students. AB - Individual drinking patterns and the perceived typical drinking patterns of close friends and reference groups were assessed in two different studies with college students. In both studies virtually all students reported that their friends drank more than they did. These effects were found across different levels of individual drinking, within different types of samples, across gender of subjects and with different types of questionnaire assessment. In addition, students' estimates of typical or average drinking within their own social living groups were significantly higher than average drinking within the group estimated from self-reports. Because of the consistent, asymmetrical pattern of reports of self and other drinking, it was interpreted that reports of others' drinking were exaggerated. These biases were particularly evident within organized social groups (i.e., fraternities and sororities) but were minimal in reference to "students in general" or "people in general." Results are discussed in terms of cognitive and motivational factors that potentially could promote or excuse excessive drinking practices among college students. PMID- 1758186 TI - Use of the CAGE scale in a population survey of drinking. AB - This article examines the use of the CAGE scale, a 4-item self-report screening test designed to identify problem drinkers, among 703 drinkers aged 18 and over interviewed in a general population survey. The results showed that 10.9% of drinkers reported two or more items affirmatively, the suggested cut-off indicative of problem drinking. This rate is similar to the percentage of drinkers who consume four or more standard drinks daily, derived from aggregate per capita consumption estimates. Factor analysis of the items showed a unidimensional scale with good psychometric properties. Other cut-offs are also compared with other alcoholism estimates. In general, the results indicated some utility of the CAGE in general population surveys. PMID- 1758187 TI - Sedative effects of ethanol at night. AB - The sedative effect of 0.7 g/kg of 100% ethanol, ingested at 9:30 PM, was investigated to examine the combined effects of ethanol and circadian sleepiness/alertness levels. Fourteen healthy young adults participated in a placebo-controlled, double-blind crossover design. Each subject, on two separate occasions (placebo or ethanol), completed multiple sleep latency testing and the repeated test of sustained wakefulness as objective measures of physiological sleep tendency, and completed the Stanford Sleepiness Scale as a measure of subjective sleepiness. The results indicate that a moderate dose of ethanol significantly increases physiological sleepiness during early morning hours even in individuals that are relatively alert at these times. Therefore, the marked reduction in alertness and related performance deficits that normally occur at night are worsened by ethanol ingestion. Sleepiness, due to any cause, and ethanol may well be a dangerous combination. PMID- 1758188 TI - Subjective feelings and changes in body sway following diazepam in sons of alcoholics and control subjects. AB - The possible generalization to diazepam of the dampened response to ethanol in sons of alcoholic fathers was evaluated in 62 sons of alcoholics (family history positive [FHP] subjects) and 62 family history negative (FHN) controls (124 men). Following challenges with placebo, .12 and .2 mg/kg of diazepam in three separate sessions, evaluation of subjective feelings and increases in body sway revealed no decreased reaction for FHPs. PMID- 1758189 TI - Close linkage of esterase-D to unipolar depression and alcoholism is ruled out in eight pedigrees. AB - Unipolar depression and alcoholism were tested for genetic linkage to esterase-D at 13q14.1. Tight linkage to esterase-D was ruled out for three phenotypes using three models of penetrance: (1) unipolar depression and alcoholism taken together as affected, (2) unipolar depression alone as affected with alcoholism considered unaffected and (3) alcoholism alone as affected with unipolar depression considered unaffected. This study does not support an earlier finding of possible linkage between the esterase-D locus at 13q14.1 and alcoholism. PMID- 1758190 TI - Effect of ethanol on insulin-stimulated glucose uptake in the isolated rat diaphragm. AB - Insulin-stimulated (0.16 and 2.56 nM) glucose uptake (GU) was studied in isolated rat diaphragms in the presence of ethanol (EtOH) 21, 42 and 84 mM as well as in diaphragms removed from rats orally treated with the drug (1.5 or 4.5 g/kg/day) for 10 or 30 days. In spite of inhibiting the base-line GU, the addition of EtOH to the incubation medium gave rise to a potentiation of the insulin effect. In the orally intoxicated series, the low-dose EtOH increased the response to 0.16 nM insulin after 10 or 30 days, no changes being observed in that induced by 2.56 nM insulin. On the other hand, the high-dose EtOH caused an increase of the base line GU which remained practically unmodified in the presence of insulin. The precise molecular basis for these phenomena is unknown. PMID- 1758191 TI - A method for maintaining and protecting chronic arterial and venous catheters in conscious rats. AB - The ability to monitor arterial blood pressure and heart rate directly, as well as to sample venous blood, or inject pharmaceutical agents intravenously is important in pharmacological studies of the cardiovascular system. The rat is a frequently used and accepted animal model for cardiovascular investigations, especially those relating to hypertension. Even though the rat is a major model for these studies, the size of the rat has made it difficult to maintain catheters for a long period of time. Although there have been previous methods available, the authors report on an improved method to implant, maintain, and protect arterial and venous catheters in conscious rats for extended periods of time. A Silastic/Tygon catheter is implanted intraarterially and intravenously, exteriorized, and protected with a spring device. Catheters remained patent throughout a 5-week period during which time direct blood pressure recordings were obtained and baroreflexes were evaluated in conscious, unrestrained rats. The described design and methods provide an inexpensive means to maintain chronically implanted venous and arterial catheters in the conscious rat. Furthermore, rats may be gang housed. PMID- 1758192 TI - Validation of a human atrial trabecular preparation for evaluation of inotropic substances. AB - Assessment of cardioactive substances is usually performed using animal tissue, with the effects being extrapolated to humans, thereby potentially introducing errors due to species differences. In order to validate the use of human atrial tissue, known positive and negative inotropic agents were tested on trabeculae obtained from patients' atrial appendages at the time of cardiac surgery requiring, cardiopulmonary bypass. Trabeculae were selected according to strict criteria: cross-sectional area less than 1.0 mm2, resting force (RF) less than 0.7 g, and developed force (DF) greater than 0.8 g. Each trabecula received only one drug in a cumulative dose manner. Where necessary, the vehicle used to dissolve or stabilize the drug solution was also tested. In addition, the relative DF of "no-drug," "time-only" controls were measured during the same time period. After adjusting for the effect of time on the preparation, relative DF was increased to 157% by dobutamine (1.5 x 10(-5) M), to 136% by amrinone (5.6 x 10(-4) M), and to 117% by ouabain (2 x 10(-7) M). The relative DF decreased with nifedipine and propranolol, with 50% inhibition for both drugs being 1.5 x 10(-7) M. Although human ventricular muscles might be more appropriate to use in order to determine the effects observed with the whole heart, they are extremely difficult to obtain on a regular basis. The results of this study show that the atrial trabecular preparation offers an acceptable alternative. PMID- 1758193 TI - Enhanced detection of hyperactivity after drug withdrawal with a simple modification of the open-field apparatus. AB - The open-field apparatus has been used to study withdrawal reactions from chronic treatments with central nervous system depressant drugs. To study the behavior of the same animal after drug withdrawal, the rats are introduced into the open field on consecutive days. Because the open field is a novel environment, the repetition could lead to false-negative results with regard to drug withdrawal. To overcome this problem, we sought a modification of the open field, using different floor-painting patterns every time the animal is observed. The most frequently observed withdrawal manifestation was hyperactivity. We verified that long-term treatment withdrawal reactions from barbital, clonazepam, and ethanol were seen more often if the rats were introduced in the modified open field. In addition, fewer animals were used here than in other trials and hyperactivity was detected more frequently in the modified open field than was sound-induced convulsions. We propose that the modified open field is more useful than the classic one for screening of drug withdrawal reactions. PMID- 1758194 TI - A connectionist model of development. AB - We present a phenomenological modeling framework for development. Our purpose is to provide a systematic method for discovering and expressing correlations in experimental data on gene expression and other developmental processes. The modeling framework is based on a connectionist or "neural net" dynamics for biochemical regulators, coupled to "grammatical rules" which describe certain features of the birth, growth, and death of cells, synapses and other biological entities. We outline how spatial geometry can be included, although this part of the model is not complete. As an example of the application of our results to a specific biological system, we show in detail how to derive a rigorously testable model of the network of segmentation genes operating in the blastoderm of Drosophila. To further illustrate our methods, we sketch how they could be applied to two other important developmental processes: cell cycle control and cell-cell induction. We also present a simple biochemical model leading to our assumed connectionist dynamics which shows that the dynamics used is at least compatible with known chemical mechanisms. PMID- 1758195 TI - Generative rules for the morphogenesis of epithelial tubes. AB - A finite elements model imitating the morphogenesis of smoothly curved tubular epithelial rudiments is suggested. It is based upon the experimentally proved assumption of the lateral (tangential) pressure between adjacent epithelial cells. The main idea of the model is that under a non-zero local curvature the lateral cell-cell pressure acquires the radial components which are absent under zero curvature. In the framework of the model we investigate the roles of initial geometry, the different coefficients relating the local curvatures and radial cell shifts, and of visco-elastical cell-cell linkages in the shaping process. We also employ the different temporal regimes (both periodical and constant) of the lateral pressure exerted and the different overall durations of the modelling. As a result, we get a set of biologically realistical shapes, almost all of them belonging to the same basical "trefoiled" archetype. Among the variables explored, shaping was most affected by the changes in visco-elastical coefficients, in the temporal regimes and in the overall duration of the modelling. The model shows that rather complicated and realistical shapes of epithelial rudiments can be obtained without assuming any initial regional differences inside cell layers. The model may be useful for understanding the principles underlying both genetical and epigenetical regulation of the morphogenesis. PMID- 1758196 TI - Feedback theory and Darwinian evolution. AB - Feedback loops can have a significant impact on biological systems that are evolving under Darwinian natural selection. Many of the striking and sometimes bizarre patterns that characterize the evolution of such systems have simple, natural explanations that involve the effects of feedback loops. The two fundamental types of feedback loops, positive and negative, have effects that are radically different: negative feedback tends to produce stability and resistance to change; positive feedback produces instability and even catastrophe. Both types of feedback loops are important in biological systems, and both can produce chaos, whose mathematical complexity often produces strange, beautiful and totally unexpected patterns that have only begun to be explored using the computational capabilities of modern electronic computers. An understanding of the patterns that can result from the effects of feedback loops can produce important new insights into the patterns that mark the evolutionary development of biological systems. PMID- 1758197 TI - Stochastic resonance in a single neuron model: theory and analog simulation. AB - Here, we consider a noisy, bistable, single neuron model in the presence of periodic external modulation. The modulation induces a correlated switching between states driven by the noise. The information flow through the system, from the modulation, or signal, to the output switching events, leads to a succession of strong peaks in the power spectrum. The signal-to-noise ratio (SNR) obtained from this power spectrum is a measure of the information content in the neuron response. With increasing noise intensity, the SNR passes through a maximum: an effect which has been called stochastic resonance, and which was first advanced as a possible explanation of the observed periodicity in the recurrences of the Earth's ice ages. We treat the problem within the framework of a recently developed approximate theory, valid in the limits of weak noise intensity, weak periodic forcing and low forcing frequency, for both additive and multiplicative noise. Moreover, we have constructed an analog simulator of the neuron which demonstrates the stochastic resonance effect, and with which we have measured the SNRs for comparison with the theoretical results. Our model should be of interest in situations where a single inherently noisy neuron is the receptor of a periodic signal, which is itself noisy, either from the network or from an external source. PMID- 1758198 TI - Evolution of discriminatory aggression in marine invertebrates. AB - Many species of sessile marine organisms show allotype-conditional aggression towards conspecifics. However, a recent theoretical analysis (Grosberg & Quinn, 1989, Evolution 43, 504-515.) was unable to find conditions permitting a discriminatory ESS against unconditionally aggressive or non-aggressive strategies. This study shows that discrimination can be an ESS if animals interact with clonemates more frequently than randomly as occurs when animals reproduce by budding of fission. This agrees well with the observation that clonal sea anemones are usually discriminators and solitary species usually non aggressive to conspecifics (Francis, 1988, Biol. Bull. 174, 241-253.) In addition, discrimination can be an ESS if discriminators retaliate against unconditionally aggressive conspecifics of the same allotype, or if the payoff to two sharers of a resource is greater than the payoff to both when sharing does not occur. PMID- 1758199 TI - The combinations of the sexes of mammalian sibs and littermates: and the possibility of adaptive control. PMID- 1758200 TI - Value of CD-1-positive cells in bronchoalveolar lavage fluid for the diagnosis of pulmonary histiocytosis X. AB - Pulmonary histiocytosis X is characterized by an accumulation of CD-1-positive histiocytosis X cells in the lung, which also can be found in the bronchoalveolar lavage fluid (BALF). However, it has recently been demonstrated that CD-1 positive cells can also be detected in BALF of patients with other interstitial lung diseases and in healthy smokers. We therefore examined the frequency of CD-1 positive cells in a pool of patients with different pulmonary disorders, according to their smoking habits and diagnoses. We have studied the bronchoalveolar lavage in patients with pulmonary histiocytosis X (n = 6), sarcoidosis (n = 88), and in 97 patients with other miscellaneous lung disorders by using the immunoperoxidase method to detect CD-1-positive cells on glass slides. All patients with histologically proven histiocytosis X displayed more than 5% CD-1-positive cells, whereas patients with other pulmonary disorders showed no more than 3.6% CD-1-positive BAL cells. The dividing line of 5% CD-1 positive cells was not influenced by patients' smoking habits. The identification of CD-1-positive cells in BALF appears to be useful in diagnosing pulmonary histiocytosis X. PMID- 1758201 TI - Treatment of chronic bronchitis with terbutaline inhaled from a cone spacer with and without positive expiratory pressure. AB - Patients with chronic bronchitis were randomly allocated to 4 weeks treatment with terbutaline 0.5 mg inhaled through a cone spacer with an expiratory resistance creating a positive expiratory pressure (+PEP group) or without (-PEP group). The patients recorded their symptoms in a diary and peak expiratory flow (PEFR) was measured before and after each inhalation. PEFR increased significantly after inhaled terbutaline both with and without PEP. The mean increase in PEFR after terbutaline inhalations was significantly greater (p less than 0.0001) in the +PEP group (24 L/min) compared to the -PEP group (17 L/min). The +PEP group had less sputum and less difficulty with coughing up sputum compared to the -PEP group. This study showed a small but significant enhancement of the bronchodilation and a beneficial effect on symptoms when inhalation of beta-2-agonist was combined with PEP in patients with chronic bronchitis. PMID- 1758202 TI - Computerized detection of respiratory events during sleep from rapid increases in oxyhemoglobin saturation. AB - A computerized search for rapid resaturation (RES)--defined as increases in oxyhemoglobin saturation (SaO2) of 3% or more within 10 s--was used to detect apneas and hypopneas during sleep by the episodes of compensatory hyperventilation following them. Results were compared to those from computerized search for desaturations (DESAT)--defined as decreases in SaO2 of 4% or more within 40 s--and to simultaneous polysomnography. We studied 30 patients with obstructive sleep apnea (OSA) with an apnea plus hypopnea index (AHI) of 30.8 +/- 6.9 (median +/- SEM) and 23 habitual snorers (HSN) with an AHI of 7 +/- 1.5. Manual scoring of polysomnography revealed 7965 respiratory events (6192 apneas, 1773 hypopneas) in OSA patients and 940 events (411 apneas, 529 hypopneas) in the HSN group. In OSA patients, the computer found 96% of events by searching for RES and 87% by searching for DESAT. The percentage of computer-found events in OSA classified as true positive was 91% for RES and 97% for DESAT. In the HSN group, 83% of polysomnographically scored events were found by RES and 55% by DESAT, with 72% of RES and 84% of DESAT being true positive. The correlation of the number of computer-found RES with the number of events from polysomnography was better in OSA (r = 0.862, p less than 0.0001) than in HSN (r = 0.722, p less than 0.001). The same was true for DESAT (OSA: r = 0.896, p less than 0.0001; HSN: r = 0.637, p less than 0.01). In conclusion, computer-found rapid resaturations are more sensitive than desaturations for the detection of respiratory events during sleep from oximetry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758203 TI - Nicardipine suppresses bronchoconstrictor actions of pharmacologic agents in guinea pigs. AB - We investigated the inhibitory effects of nicardipine on airway smooth muscle constriction in the guinea pig via both in vitro and in vivo preparations. In the in vitro studies, we created dose-response curves of the excised tracheal strip. The increase in respiratory overflow produced by leukotriene (LT) D4 was measured in the in vivo preparation. In the organ bath, nicardipine (1-12 micrograms/ml) significantly inhibited constriction of the isolated tracheal spiral strip induced by 7 different agonists, acetylcholine (Ach), histamine (HA), serotonin (5-HT), prostaglandin F2 alpha (PGF2 alpha), slow-reacting substance of anaphylaxis (SRS-A), and LTC4 and LTD4. Compared to nifedipine and verapamil (data in the literature), the inhibitory potency of nicardipine on the constriction of the isolated guinea pig tracheal strip is 100-1,000 times greater. In the in vivo studies, nicardipine (50 and 100 micrograms/kg) significantly attenuated the LTD4-induced increase in respiratory overflow. These results suggest that nicardipine inhibits bronchoconstrictor-induced constriction of airway smooth muscle both in vitro and in vivo, and that it is a potent bronchodilator. The inhibitory characteristics of nicardipine may prove to be applicable clinically. PMID- 1758204 TI - [The hepatotoxicity of tuberculosis treatment]. AB - BACKGROUND: The hepatic toxicity of antituberculous drugs used for the therapy of initial cases was evaluated, assessing the incidence and severity and its relation with each drug, age, other associated hepatic risks and the chronological time of therapy. METHODS: 1235 patients with tuberculosis were prospectively assessed with a protocol including periodical clinical and laboratory controls. RESULTS: Hepatic toxicity was found in overall 16.5%, with 3.5% of severe forms and need for a definitive change in therapy in 1.5%. Differences in toxicity between the 6-month and the 9-month schedules were not found. The most commonly incriminated drugs was isoniazid followed by pyrazinamide. All severe forms presented with symptoms, although some were nonspecific and insidious. Other associated hepatic risks implied an increased frequency of iatrogenic reactions. Age did not have a determining influence in severe forms, which predominantly developed within the first two months of therapy. CONCLUSIONS: Moderate, transient and asymptomatic increase in transaminase activity not requiring a change a therapy is common. Severe and dangerous forms are uncommon and predominate at the beginning of therapy and in persons with associated hepatic risk factors. Therefore, although the clinical controls should be maintained throughout treatment, laboratory controls should only be carried out during the first two months, except when symptoms are present or in patients with associated hepatic risk factors, where they should be more frequent and carried out throughout treatment. PMID- 1758205 TI - [The investigation of the contacts of the tuberculous pediatric patient]. AB - BACKGROUND: Results of contacts investigation of tuberculous pediatric patients, usually non-infectious, are shown. Their relationship to the clinical situation on index case and the intimacy of exposure is analyzed. METHODS: 714 contacts of 111 pediatric cases (53 category II and 58 category III, according to the American Thoracic Society classification). The tuberculin skin test with 2 units of PPD-RT23 was used to identify the infected persons. Chest radiography, sputum smear and culture examination were used to diagnose current pulmonary disease. According to the intimacy of exposure to index case, contacts were defined as household, close or sporadic contacts. The possible association with clinical situation of index case and intimacy of exposure was analyzed. RESULTS: 41 new cases of tuberculosis were detected, 7 of them were infectious. Prevalence of tuberculous infection among contacts was 44%. Quimioprofilaxis was indicated to 126 contacts. The prevalences of infection and disease according to clinical situation and degree of contact did not differ significantly. CONCLUSIONS: it is advisable to investigate the contacts of tuberculous pediatric patients, even in cases of tuberculous infection without disease; the investigation must include close and sporadic contacts. PMID- 1758206 TI - [Vaccination in immunodepressed patients]. PMID- 1758207 TI - [Meningeal myelomatosis as an exclusive form of recurrence in a case of IgA lambda myeloma in complete systemic remission]. AB - Meningeal myelomatosis is an extremely rare clinical presentation generally associated to terminal states of the disease and is more frequent in the presence of peripheric plasmocytosis or leukemia of the plasmatic cells. Diagnosis requires its demonstration in the cephalorhachidian liquid and its monoclonal secretion. A case of relapse of meningeal myelomatosis in a patient with multiple IgA-lambda myeloma is presented in which the systemic disease fulfilled the criteria for complete remission. PMID- 1758208 TI - [The diagnosis and treatment of catheter-produced sepsis]. PMID- 1758209 TI - [Primary lymphoma of the thyroid]. PMID- 1758210 TI - [The management of a hospital crisis]. PMID- 1758211 TI - [Ibuprofen and antihypertensive drugs]. PMID- 1758212 TI - [A high-grade T-cell non-Hodgkin's lymphoma in a patients with tuberous sclerosis treated with hydantoins]. PMID- 1758213 TI - [Diabetic dorsal radiculopathy]. PMID- 1758214 TI - ADL: an integrated database for filing and study of malignant lymphoma patients. AB - The filing of clinical data must comply with purposes of logical organization for comparisons and evaluations. ADL (Archives of Data on Lymphomas) is an application program of dBASE III plus (Ashton-Tate) for personal computers, especially suitable for filing and studying patients afflicted with malignant lymphoma. It is subdivided into four data files: general data (private data, stage, therapy); disease data (sites of disease by tests and body area); immunological data (lymphocyte subpopulations, globulin and immunoglobulin dosage, delayed hypersensitivity skin tests); lost patients (register of patients not seen for at least 1 year). It has many utilities (descriptive statistics, clinical report, export service). Congruence checks and verification of names and dates input are included. This program stands as a valuable alternative to more traditional filing systems. PMID- 1758215 TI - Development and validation of HEPAR, an expert system for the diagnosis of disorders of the liver and biliary tract. AB - HEPAR is an expert system in the field of hepatology which can be used as a supportive tool in the diagnosis of disorders of the liver and biliary tract. The representation language employed in HEPAR consists of production rules with object-attribute-value triples. In the system, medical diagnosis is modelled according to the strategy which is clinically used in this field. The patient's disorder is assessed in two stages. In the first stage, available data from medical interview, physical examination and simple laboratory tests are used to determine whether the disorder is hepatocellular or biliary obstructive in nature, and whether benign or malignant features are present. In the second stage the system produces a subset of possible diagnoses out of a set of more than 80 disease categories, using additional data from supplementary tests. The results of the first stage classification cause considerable pruning of the search space. In this paper the structure, development process and approach followed in the validation of the HEPAR system are described. The results of a recent performance validation study using data from 181 consecutive patient cases are discussed. PMID- 1758216 TI - The wavelet transform and its applications to phonocardiogram signal analysis. AB - The wavelet transform, which is the decomposition of a signal into a set of independent frequency channels, is shown to be a useful diagnostic tool in the analysis of heartbeat sounds. In particular, the wavelet transform enables the experimentalist to obtain qualitative and quantitative measurements of time frequency characteristics of phonocardiogram (PCG) signals. PMID- 1758217 TI - Computerized medical records: defining a standard without the computer. AB - The inevitable computerization of medical records may be a boon or a hindrance to the practice of medicine. A comprehensive view of the project is essential for its success. Definite goals for the computerized medical record are stated to this end. An argument is presented for keeping the structure of the medical record separate from any specific requirements of technology. An elegant structure for medical records is proposed, independent of any computer system and requiring a minimum of definitions or special characters. The roles of clinical specialists (such as physicians and nurses), medical records specialists, administrators, accountants, and computer architects (hardware and software) are defined. In particular, the tasks of lexicon and template creation are defined and emphasized as urgent and ongoing challenges for specialty organizations. PMID- 1758218 TI - How to approach a hospital information system as sampling frame. Selection of patients with a percutaneous renal biopsy. AB - The paper describes the four steps that have to be taken in the process of using a hospital information system as sampling frame: step 1, description of the medical routine and registrations related to the study population; step 2, defining the design and criteria for selection; step 3, creating the datafile and step 4, validating the datafile. To illustrate these four steps a detailed description of the selection of patients with a percutaneous renal biopsy is given, using the central database of Leiden University Hospital. All registrations relating to patients undergoing a percutaneous renal biopsy in 1985 and 1986 were taken into account and combined in defining the design and criteria for selection. The selection resulted in 182 patient-records, of which 177 were compared with the medical file. Overall 150 percutaneous biopsies were confirmed. Hospital Information Systems are in principle useful as sampling frames for clinical research. However, to use these systems successfully in selecting a study population intensive mutual consultation between clinicians, clinical epidemiologists, database experts and administrative personnel is required. PMID- 1758219 TI - A personal computer network system for equitable allocation of cadaver organs. AB - We developed a personal computer network system for the equitable allocation of cadaveric organs. This network consists of a host computer (IBM PS55 model 5570 T) and various kinds of personal computers manufactured by many different computer makers in Japan. The merits of our personal computer network include lower cost and an easy access to the host computer from all the centres participating in this network while using their own favourite personal computers. Among the programs made for allocating cadaveric organs, we present in this paper the program for livers. This program was developed with a modified version of the logic developed by Starzl et al. The grade modification for the United Network for Organ Sharing (UNOS) in the United States was used as the basis for classification of medical urgency. Our program weighed the factors of medical urgency, compatibility of blood group and waiting time. Distance factors were omitted because of the smaller area of the network compared to that of UNOS. This computer network would be linked to other computer networks in creating a national organ procurement and transplant network in Japan, in order to help them to catch up with other advanced transplant countries. Such an equal and objective computer system should allow organ transplantation to become more widely accepted. PMID- 1758220 TI - Construction of diagnostic rules based on assessments of subjects. AB - This paper is based on assessments of subjects which are not defined by formal procedures. Logically structured assignment rules are constructed which are stable over time and which have a low number of disagreements with the assessments of the subjects. Recent results obtained from a computational learning theory show that the proposed construction of rules leads with high probability to rules with similar performances on large enough learning and validation sets of subjects. The construction of a set of stable rules is illustrated by using as a case study the psychophysiological, personality and speech behaviour data of a repeated-measures Type A behaviour study. This case study is also used for a discussion of the issue of biased ratings in the presence of assessments which are not defined by formal procedures. PMID- 1758221 TI - Integrating a medical database and advisory system. AB - A system is described which incorporates the use of a diagnostic and treatment advice expert system into the routine information-handling functions of a surgical breast clinic. The main focus of the system is on identification and management of non-malignant breast disease. The advisor is linked with a clinical database which is used to hold summary case notes, and from which reports forming the basis for audit of case-mix and resource utilization can be produced. The system uses backward chaining of extended production rules and a relational database, and runs on a desktop microcomputer. PMID- 1758222 TI - [A comparison of 2 curricula: clinical skills during the year of clinical medicine studies]. PMID- 1758223 TI - [Antihypertensive treatment reduces the risk of stroke even in elderly hypertensive patients]. PMID- 1758224 TI - [Asymptomatic primary hyperparathyroidism: surgery or follow-up?]. PMID- 1758225 TI - [Can we believe children?]. PMID- 1758226 TI - [Cannulas and gloves reduce the risk of blood contamination]. PMID- 1758227 TI - [Arthroscopy--a diagnostic technique with increasing therapeutic use]. PMID- 1758228 TI - [Fine needle renal biopsy is less informative than biopsy using thicker needles]. PMID- 1758229 TI - [Erythropoietin made surgery for aortic coarctation possible in a Jehovah's witness patient]. PMID- 1758230 TI - [Wolfgang Amadeus Mozart. Medical and musical reflections on the 200th anniversary of his death]. PMID- 1758231 TI - [Wide cooperation is necessary for diagnosis and treatment of torture injuries]. PMID- 1758232 TI - [Biosensors--future analytical technology?]. PMID- 1758233 TI - [Mikhail Bulgakov, physician and writer--a year of centenaries. Manuscripts do not burn]. PMID- 1758234 TI - [Current state of treatment and prevention of gastroduodenal side effects of non steroidal antirheumatic drugs]. AB - In spite of optimized antirheumatic treatment, NSAID-related mucosal lesions ranging to bleeding ulcers occur mainly in the stomach and less frequently in the duodenum. With continued NSAID therapy, overt mucosal lesions can be treated with Omeprazol or H2 blockers. The efficacy of these medications may be correlated with their acid-inhibiting potency. Antacids have not as yet been sufficiently tested for this indication. Although prostaglandin derivatives are effective, in high doses they may cause diarrhea. Despite their good efficacy, they should therefore not be employed as a first choice for this indication. NSAID-induced mucosal lesions "owe" their development to local iatrogenic prostaglandin deficiency. Through co-medication with Misoprostol in low dosage, NSAID mucosal lesions and ulcers are prevented without the occurrence of significant undesirable Misoprostol effects. H2 antagonists and Omeprazol have a protective effect on the mucosa solely in the duodenum. Antacids have not as yet been tested successfully for this indication either. Elderly patients with a medical history of ulcers frequently develop silent NSAID ulcers. Any NSAID therapy necessary for these high-risk patients should therefore always be accompanied by at least a sufficient mucosal protection therapy. PMID- 1758235 TI - [Circulating "tumor markers" in gastrointestinal tumors]. AB - Tumor markers (TM) of the neoplastic cell can be divided into non-shedded substances and antigens shedded in blood, urine or other body fluids. For clinicians circulating TM are more important. All relevant circulating TM are not useful in screening of asymptomatic patients because of insufficient sensitivity and specificity. With caution they are useful in the observation of risk groups. Circulating TM have their main significance as additional parameters in monitoring symptomatic patients with malignancies. Several follow up determinations are more important than one single measurement. During follow up of tumor patients TM should not be checked automatically if there are no diagnostic or therapeutical consequences. The clinically most important circulating TM in non-hormone secreting tumors of the gastrointestinal tract are the oncofetal antigens CEA and AFP and antigens defined by monoclonal antibodies e. g. CA 19-9 and CA 72-4. AFP is the primary TM in hepatocellular carcinoma, often elevated in hepatoblastoma and always normal in cholangiocellular carcinoma. CEA is the TM of first choice in patients with colorectal carcinomas and liver metastasis. CA 19-9 is TM of first choice in pancreatic carcinoma and additionally of diagnostic value in cholangiocellular carcinoma and tumors of the bile ducts. In cancer of the stomach CA 19-9 and CEA are secondary TM in combination with CA 72-4 as primary TM. Care should be taken that slight and moderate elevations of TM can be observed in benign diseases of liver, pancreas and bowel. PMID- 1758236 TI - [Extra-gastric non-Hodgkin's lymphomas of the abdomen--the role of surgical treatment]. AB - A multimodality approach offers the best chance for treatment of Non-Hodgkin lymphoma. Surgery, radiation therapy, and/or chemotherapy when used in combination offer better response and longterm survival rates. Surgical therapy offers good results in stage I and II according to the Ann Arbor classification. Aim is the excision of the tumor with the removal of lymph nodes. The best treatment in stage III and IV is chemotherapy and radiation followed by surgical tumor reduction. Complications like perforation or bleeding occurred while the patients received either chemotherapy or radiotherapy. Resection of the Non Hodgkin lymphoma prevented the complications of hemorrhage and perforation associated with chemotherapy and radiation. PMID- 1758237 TI - [Neurotensin liberation during the consumption of mineral water from Bad Mergentheimer Karlsquelle]. AB - The contraction of the gallbladder mainly mediated by CCK after oral administration of pharmacological doses of magnesium sulfate is familiar. The same applies to the cholekinetic action of courses of sulfatic mineral water treatment. It was demonstrated in 12 patients in a controlled study that besides other known secretions of gastrointestinal hormones, there is also a significant rise of the plasma level of neurotensin when Bad Mergentheimer Karlsquelle mineral water containing sulfate (3.7 g SO4/l) is drunk on an empty stomach (300 ml, 26 degrees C). This was significantly greater (basal values 6.8 +/- 4.1 pg/ml and a maximum of 15.7 +/- 8.1 pg/ml after 40 min) than in a control group consisting of the same patients who had drunk tapwater. Whereas the involvement of the neuropeptide neurotensin in the regulation of the exocrine functions of the pancreas has been established, its effect in the regulation of gallbladder contraction is probably of rather minor significance compared to CCK. PMID- 1758238 TI - [Goblet cell carcinoid of the vermiform appendix]. AB - The goblet-cell-carcinoid of the appendix vermiformis lies somewhat between the carcinoid and the adenocarcinoma of the appendix concerning the biological behaviour and the histological characteristics. Referring an own well documented case (76 are well known in the available literature) the importance of the very conscientiously managed histological examination of each appendix specimen is emphasized with regard to the 5-year-survival of 73%. PMID- 1758239 TI - [Collagenous duodenitis and ileitis in a patient with collagenous colitis]. AB - Collagenous colitis is a disease accompanied by chronic watery diarrhea, of which the etiology is unknown. Sporadic cases of collagen deposits in the upper gastrointestinal tract are meanwhile reported. We here report the case of a 53 year-old female patient suffering from collagenous colitis with additional collagen deposits in the duodenum and ileum. The favourable effect of a therapeutical trial with bismuth nitrate is described. PMID- 1758240 TI - [Effect of succinylcholine on recovery of atracurium-induced neuromuscular blockade]. AB - If muscle relaxation is inadequate at the end of surgery, a transient increase in neuromuscular (NM) blockade should be needed to facilitate closure. Succinylcholine is the only agent of short duration available currently and could be used in the just mentioned circumstance. Therefore, the study was designed to investigate the effects of succinylcholine on the recovery of atracurium-induced NM blockade. Sixty-four female patients who underwent elective surgery under general anesthesia were allocated into 6 groups. Before anesthesia, no patient had received drugs which affect NM transmission. In all patients anesthesia was induced with thiopental, diazepam and fentanyl and maintained with 50% nitrous oxide in oxygen and 0.5-1.5% isoflurane. During anesthesia, blood pressure and electrocardiogram were monitored and end-tidal CO2 was maintained at 30-40 mmHg. Control records of the integrated electromyography responded to train-of-four supramaximal stimulation using a Datex Relaxograph were obtained after induction of anesthesia before a block was produced with an initial dose of succinylcholine 1.0 mg in group I (n = 8) or atracurium 0.4 mg/kg in groups II-VI. On first twitch (T1) recovering to 50% of control, 0.4 mg/kg, 0.6 mg/kg, 0.8 mg/kg, 1.0 mg/kg and 1.2 mg/kg of succinylcholine were given in groups II (n = 11), III (n = 14), IV (n = 11), V (n = 10), VI (n = 10) respectively. It was seen that succinylcholine 0.4 mg/kg antagonized NM blockade by atracurium but at 0.6 mg/kg, 0.8 mg/kg, 1.0 mg/kg, 1.2 mg/kg it enhanced that.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758241 TI - [The effect of succinylcholine on the recovery of atracurium-induced neuromuscular blockade]. AB - At the end of abdominal surgery, a brief but profound neuromuscular blockade may be needed to facilitate closure of abdominal wall. Succinylcholine (Sch) was the agent used in this regard before. This study was undertaken to observe the effect after administration of Sch (1 mg/kg) at various levels of recovery from atracurium. 40 ASA I or II patients undergoing elective surgery were randomly assigned to one of four groups with 10 in each. Anesthesia was induced with thiopental 5 mg/kg and Sch 1.5 mg/kg i.v., and maintained with 0.7% isoflurane (end-tidal concentration) and 50% N2O in O2 The electromyographic response of the hypothenar muscle was recorded in response to supramaximal train-of-four stimuli delivered to the ulnar nerve at 20 s intervals using a relaxograph (Datex). Control records were obtained after induction of anesthesia. When the first twitch (T1) had recovered above 50% from the intubating dose of Sch, atracurium 0.5 mg/kg was administered. Spontaneous recovery of T1 was observed. Patients in group I received 1 mg/kg of Sch, when T1 returned to 20% and those in groups II, III, and IV received the same dose of Sch when T1 returned to 40%, 60% or 80% of control respectively. The response was observed at 20s intervals for at least 5 min after the administration of Sch. It was regarded as effective response if the T1 returned to less than 5% of control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758242 TI - [Initial washout time of inhaled anesthetic agents]. AB - Recovery of inhalation anesthesia is generally considered the inverse of induction. While other factors remain unchanged, the rate of elimination of an inhaled anesthetic agent with a lower solubility such as nitrous oxide (N2O) is faster than one with a high solubility. Therefore, at the end of surgery it is a common practice to discontinue the volatile agent prior to discontinuing N2O. However, the results of our routine monitoring of end-tidal concentrations of anesthetics and physiological gases by employing a mass spectrometer lead us to question the practice. We studied 24 non-premedicated ASA I/II patients requiring endotracheal intubation with an anesthesia time over 2 h. All patients were mechanically ventilated at an appropriate tidal volume and respiratory rate to maintain an ETCO2 of 35-38 mmHg with an anesthetic mixture of 40% O2 and 60% N2O and isoflurane (Forane). At the end of surgery, both N2O and isoflurane were discontinued simultaneously and total oxygen flow was increased to 6 or 10 l/min by random. The exhaled partial pressure of both inhaled anesthetic agents were assessed at the time of anesthetic termination, after 1, 2 min, and then every 2 min up to 20 min or at the time of extubation. The results obtained were plotted against real time using two different scales. Despite the marked difference in their plasma solubilities, these two inhaled anesthetic agents reached to low exhaled partial pressure that had no clinical significance about ten minutes after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758243 TI - [Intravenous propofol as a supplement in epidural anesthesia]. AB - Under study were thirty patients of ASA class I-II scheduled for lower abdominal and lower extremities surgery. Premedication included intramuscular injection of pethidine, atropine and prochlorperazine. Epidural anesthesia was accomplished with 12-15 ml 2% lidocaine with epinephrine (1:80,000). Thirty minutes later, when blood pressure returned to control value, patients were put to sleep by 2 mg/kg propofol and the sleep was maintained with continuous infusion of propofol at a rate of 6 mg/kg/h. Infusion rate was adjusted when necessary. Patients breathed room air spontaneously through the whole course of anesthesia. The results showed that all patients fell to sleep within 28.3 +/- 2.7 s after intravenous injection of propofol 2 mg/kg. Sleeping dose was satisfactorily achieved using a mean infusion rate of 6.1 +/- 1.7 mg/kg/h. The mean time from the end of the infusion of propofol to opening of the eyes on command and telling the correct date of birth were 7.9 +/- 2.8 min and 9.9 +/- 3.8 min respectively. Two minutes after injection, there were significant decrease in systolic pressure, diastolic pressure, cardiac output, and stroke volume with a mean of 17.9 +/- 3.8%, 18.8 +/- 3.3%, 7.6 +/- 0.5% and 11.1 +/- 1.9% respectively. Two patients (7%) developed apnea after 2 mg/kg propofol which was considered to be the most serious side effect. Propofol infusion had to be stopped in 13% patients due to a 30% fall of arterial blood pressure during maintenance. In the recovery stage, no other complications were noted except one patient who felt dizziness. Propofol, used as the supplementary sedative, provides satisfactory result for surgery under epidural anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758244 TI - [Prolongation of hyperbaric bupivacaine spinal anesthesia with clonidine]. AB - Recent reports showed that spinal clonidine might provide satisfactory analgesia via a nonopioid mechanism. In this study we tried to evaluate the prolongation of analgesic effect of the hyperbaric bupivacaine spinal anesthesia with clonidine. 40 ASA class I-II patients scheduled for TURP were randomly classified into two groups of 20 each. In saline group, 3 ml 0.5% hyperbaric bupivacaine plus 1 ml normal saline was given. In clonidine group, 1 ml (0.15 mg) clonidine in addition to 3 ml 0.5% bupivacaine was given. All the patients were placed in lateral position and dural puncture was made at the L3-4 interspace using a 25G spinal needle. Assessment of the sensory blockade by "pinprick" and motor blockade by Bromage scale and measurement of blood pressure and heart rate were performed after injection. All data were analyzed by Student's t-test. A p value less than 0.05 was considered statistically significant. Our results showed that the highest sensory blockade level and the time required for maximal spread of the sensory blockade were of no significant difference between groups. The mean time for two segments regression and mean time for regression to L2 were significantly greater in the clonidine group than in the saline group (p less than 0.001). Motor blockade was also prolonged in the clonidine group than the clonidine group. Side effects such as hypotension (10 in clonidine gp vs 4 in saline gp) and bradycardia (4 clonidine gp vs 2 in saline gp) commonly occurred in the clonidine group, but all patients could be effectively treated with ephedrine and atropine respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758245 TI - Incidence of post-dural puncture headache with 25-gauge Quincke spinal needle. AB - A retrospective study was undertaken in patients who received spinal anesthesia in past two years in order to find out the incidence of post-spinal headache. There were 3729 cases, 1997 males and 1732 females. Seventy-two patients were noted to have post-spinal headache of whom twelve were male and sixty were female. The overall incidence was 1.93%. Incidence was 0.6% and 3.5% in male and female groups respectively. With respect to the type of surgical procedures in female group, patients undergoing Cesarean section had a higher incidence than those who received other surgical procedures, being 4.8% and 1.5% respectively. In conclusion, female patients were noted to have higher incidence of post-spinal headache, particularly in patients undergoing Cesarean section. PMID- 1758246 TI - [The possible mechanism of fentanyl-induced muscle rigidity]. PMID- 1758247 TI - [Intraoperative evoked potentials monitoring during spine surgery]. PMID- 1758248 TI - [Seizure induced by small dose of fentanyl]. PMID- 1758249 TI - [Can diclofenac sodium control the pain associated with uterine contraction after cesarean section?]. PMID- 1758250 TI - Comparison of inguinal nerve block and intravenous fentanyl in relieving postinguinal herniorrhaphy pain for pediatric outpatients. AB - The purpose of this study was to compare the effects of ilioinguinal/iliohypogastric (IG/IH) nerve block and intravenous fentanyl for pain control following inguinal herniorrhaphy in pediatric outpatients. Seventy five ASA physical status I and II children (aged 1 to 10 yr) with unilateral inguinal herniorrhaphy under general anesthesia were randomly divided into three groups. Group A received IG/IH nerve block, using 0.25% bupivacaine (1 mg/kg) immediately after induction. Group B received intravenous fentanyl (1 microgram/kg) immediately after induction. Group C received only general anesthesia as control. At postanesthetic care unit (PACU), we recorded the degree of pain/or discomfort at 5, 15, 30, 45 and 60 min using modified Hannallah's scoring system after the patient was fully awake. The degree of recovery was also evaluated using Steward's scoring system. After discharge, the parents were interrogated about the condition of child within 24 h by telephone. Follow-up items raised included vomiting, drowsiness, pain and shivering. Our results showed that children in both study groups had lower pain score than those in the control group, and in the fentanyl group children had lower pain score than in the nerve block group during the first 30 min at PACU. The recovery time was also longer in the fentanyl group. There was no significant difference among the three groups regarding the raised items over telephone interrogation. In sum, inguinal nerve block was effective for postoperative pain relief in children undergoing inguinal herniorraphy. We also suggested that small dose of intravenous fentanyl would serve as an easy, simple and effective means for relieving postinguinal herniorrhaphy pain during the first 30 min of the initial postoperative period. PMID- 1758251 TI - Acute normovolemic hemodilution in coronary artery bypass graft surgery. AB - Twenty patients undergoing coronary artery bypass graft (CABG) surgery in April through May, 1990 in our hospital were included in this study to evaluate the merits and practicability of autologous blood transfusion. About 1,000 ml of arterial blood were collected via a radial arterial line and stored in a plastic bag containing CPD solution immediately after induction of anesthesia. Colloid or crystalloid solution was used to replace the volume deficit after the blood sampling. At the end of cardiopulmonary bypass and after adequate reversal of heparinization by protamine, the blood previously sampled was re-transfused to the patient via a peripheral venous line. Thirty patients undergoing CABG surgery, who did not receive autologous blood transfusion from February to June, 1990 save April and May were assigned as control. Comparison of the data between the two groups was made using the Student's t-test. It was found that the intraoperative acute normovolemic hemodilution could lower the hematocrit by approximately 12%. Packed red blood cells (PRBC) given intraoperatively in the autologous group was only 2.0 +/- 0.4 units whereas it was 5.3 +/- 0.7 units in the control group (p less than 0.001). Fresh frozen plasma (FFP) given intraoperatively in the autologous group was only 1.8 +/- 0.5 units whereas it was 6.6 +/- 0.7 units in the control group (p less than 0.001). The amount of platelets given intraoperatively in the autologous group was 1.9 +/- 1.0 units against 9.3 +/- 1.4 units in the control group (p less than 0.001). Thus, acute normovolemic hemodilution in CABG surgery decreased intraoperative requirement of bank blood components including PRBC, FFP and platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758252 TI - [Clinical assessment of laryngeal mask airway in general anesthesia with spontaneous breathing]. AB - The laryngeal mask airway (LMA) is a new form of oropharyngeal airway that provides an alternative to endotracheal intubation and face mask anesthesia in certain cases. Once the patient is adequately anesthetised, it can be inserted blindly without recourse to laryngoscopy. The advantages over standard mask anesthesia are: better airway control, minimal leakage of anesthetic gases, and it frees the anesthetist's hands, as no mandibular support is needed. LMA does not guarantee against the risk of aspiration and it is not recommended for use in patients who may have risk of gastric regurgitation. Our preliminary study revealed that a clear and clinical satisfactory airway was obtained in 98.2% of patients. According to the intraoperative respiratory minute volume and arterial blood gases, the patency of the airway did not deteriorate during the course of the anesthesia. Blood pressure and heart rate were compared on induction in group I and II. Succinylcholine 1 mg/kg, thiopentone 4-6 mg/kg and fentanyl 2 micrograms/kg were used in group I while using the same dosage of succinylcholine and thiopentone without fentanyl for group II. We found no significant differences in vital signs between the two groups. PMID- 1758253 TI - [Efficiency of patient-controlled analgesia versus conventional analgesia in patients after thoracotomy]. AB - The patients received thoracotomy usually suffered from significant severe pain postoperatively, which accompanied with impaired pulmonary function or increased incidences of atelectasis and pneumonia. So adequate analgesia for those patients is indicated. The purpose of this study is to investigate the efficiency of patient-controlled analgesia (PCA) and determine whether it is better than conventional analgesia or not. Twenty-six patients, ASA physical status class I and II, were randomized into two groups: PCA and intramuscular (IM). The effect on pain relief was assessed by a visual analogue pain scale (VAPS) q 4 h postoperatively for two days. Forced vital capacity (FVC) and the questionnaire of nocturnal sleep disturbance by pain were evaluated preoperatively, the first, second postoperative mornings. As result of this study, the patients of PCA group get less pain than IM group after the first and second days of surgery. VAPS values are 3.7 +/- 1.1, 2.8 +/- 0.8 and 6.1 +/- 0.9, 5.3 +/- 1.1 respectively pertaining to PCA and IM groups (p less than 0.05). The patients of IM group get more disturbance of nocturnal sleep than PCA group at initial two nights of postoperation as well (p less than 0.05). It is manifest to look out the significant difference between these two groups in accordance with FVC ratio records of post-surgery vs presurgery at initial two days after surgery on the subject of respiratory function recovery. PCA group are 46.46 +/- 7.29%, 52.25 +/ 8.32% in a condition of more progress on lung function recovery than IM group of 38.13 +/- 10.25%, 42.15 +/- 7.82% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758254 TI - [A comparison of patient-controlled analgesia with traditional intramuscular administration for postoperative pain relief]. AB - The use of a disposable non-electronic patient-controlled analgesia (PCA) device (Baxter) was evaluated in this study. Every patient under trial was instructed thoroughly how to use the PCA device before operation. The PCA device delivers a 25 mg IV injection of pethidine upon patient demand with a delay of 15 min between allowable administrations. The degree of patient satisfaction, the drug consumption, and the duration of using analgesia were compared with those in IM pethidine group. The results showed that, in the PCA group, the duration of using analgesic was longer; the drug consumption was greater (especially during the first 20 h after operation); and the degree of patient satisfaction was higher. The series comprised a total of 54 patients, 14 of whom complained of mild dizziness or nausea which did not require specific treatment. In sum, giving analgesic by the Baxter PCA device was a safe and effective alternative for IM analgesic in postoperative pain control. PMID- 1758255 TI - [One lung anesthesia]. PMID- 1758256 TI - [Initial airway management of laryngotracheal trauma]. PMID- 1758257 TI - [Succinylcholine-induced prolonged apnea and hyperthermia in a patient with organophosphate insecticide poisoning]. PMID- 1758258 TI - [Anaphylaxis induced by electrodes of electrocardiogram]. PMID- 1758259 TI - [Effects of drug dose on spinal anesthesia with isobaric tetracaine]. AB - A protocol similar to that established in our previous reports was used in the current study. A total of 128 demographically compatible patients were studied using various tetracaine dosages in 2 ml isobaric solution; fifty patients (group I) received 10 mg, 46 patients (group II) received 15 mg, and 32 patients (group III) received 20 mg. Except for the drug dosage, an identical technique was employed for every patient in the study. The highest sensory levels were T7 (median, range T5-12) for group I, T5 (median, range T3-8) for group II, and T4 (median, range C8-T5) for group III, with an onset time of 7.08 +/- 1.16, 10.37 +/- 1.69 and 11.14 +/- 1.85 min respectively. The above differences are statistically significant (p less than 0.05). However the differences between their onset times to the T10 level were not statistically significant (p greater than 0.05). The 2-segment regression times were 180.5 +/- 53.44 min for group I, 216.4 +/- 37.3 min for group II and 248.7 +/- 38.6 min for group III. The difference between group I and group II as well as group I and group III were statistically significant (p less than 0.01) but not significant between group II and group III (p greater than 0.05). The onset times of maximum motor blockade assessed by modified Bromage scale were 5.42 +/- 1.59, 5.28 +/- 1.36 and 5.37 +/- 1.42 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758261 TI - Epidural tramadol for postoperative pain relief. AB - Forty-two surgical patients were given epidural tramadol for control of postoperative pain. They were randomly assigned to three groups: group 1 (n = 15), in which 25 mg of tramadol were given; group 2 (n = 13), in which 50 mg of tramadol were given; and group 3 (n = 14), in which 75 mg of tramadol were given. When the patients complained of wound pain, epidural tramadol was given. Heart rate, blood pressure, respiratory rate, oxygen saturation (SpO2), sedation scale, motor blockade, verbal rating scale, subjective grading, and visual analogue pain scale (VAPS) were measured and recorded before the tramadol administration, at 5 and 15 min, and at 1, 2, 4, and 8 h after the tramadol administration. Only 26.6% of the patients in group 1 had significant relief of pain. The rest of them needed at least one incremental dose of 25 mg of tramadol. The baseline VAPS of the patients in group 2 was 8.9 +/- 2.0. It became 5.46 +/- 3.0 (p greater than 0.05) 15 min after tramadol was given, and dropped further to 1.9 +/- 1.8 (p greater than 0.05) 2 h later. The average duration of pain relief was 12.0 +/- 5.9 h. In group 3, the initial VAPS was 8.14 +/- 1.9. It decreased to 4.28 +/- 1.8 (p greater than 0.05) 15 min, and further dropped to 1.7 +/- 0.9 (p greater than 0.05) 2 h following tramadol administration. The average duration of pain relief was 11.3 +/- 4.8 h. The common side effects of tramadol such as dizziness, nausea, and dry mouth, were most frequently found in group 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758260 TI - Effect of physostigmine on the loss of consciousness induced by midazolam, etomidate and althesin. AB - The effect of physostigmine, a cholinesterase inhibitor, on the loss of consciousness induced by three different intravenous induction anesthetics, namely midazolam, etomidate and althesin at ED50, was studied in three comparable groups of patients. Ten min before induction, the first and second groups received physostigmine 8 micrograms/kg and 16 micrograms/kg, respectively, and the third group received 2 ml of saline solution. Physostigmine 16 micrograms/kg resulted in a significant decrease in the percentage of unconscious patients with midazolam (from 50% to 10%), but it did not modify the incidence with etomidate or althesin. Physostigmine at doses of 8 micrograms/kg and 16 micrograms/kg could cause 6.7% and 10% nausea, respectively. Although the mechanism of the drug interaction of physostigmine and midazolam is unclear, physostigmine could be used clinically to reverse post-anesthetic somnolence induced by midazolam. PMID- 1758262 TI - [The study of cancer pain and its correlates]. AB - From August 1989 to December 1990, we collected 1523 cases of malignancy at Tri service General Hospital (TSGH), and 470 cases (30.9%) of these malignancy had pain complaint. Moreover, we found that 68.1% (79/116 cases) of malignancy with bony metastasis had pain complaint. These informations were obtained from medical records. By counting the site of these 1523 cases, the leading sites in sequence were lung (207 cases), stomach (164 cases), cervix uteri (132 cases), breast (117 cases) and colon (91 cases). Regarding the incidence of cancer pain among these malignancy, bone cancer had the highest incidence (75.0%), followed by tongue (66.7%), brain (65.7%), liver (62.3%) and pancreas (60.0%). There was no difference of the incidence of cancer pain between male and female. The incidences of cancer pain in different age groups were different; the young patients had higher incidence than elderly patients. The analgesics for cancer pain used most frequently by physicians at TSGH were nonsteroid anti-inflammatory drugs and meperidine. Although the therapeutic management of cancer pain has been advancedly developed, we found that the treatments of cancer pain by physicians at TSGH were not aggressive enough. Therefore, promotion of the concept in advanced pain control and techniques is our important task in the near future. PMID- 1758263 TI - A comparison of umbilical venous blood levels of neuropeptide Y and catecholamines between cesarean section and normal spontaneous delivery. AB - This study was designed to determine the presence and different levels of placental neuropeptide Y (NPY) in women at parturition between normal spontaneous delivery (NSD) and cesarean section (C/S) under spinal anesthesia and to compare it with the level of catecholamines. Umbilical vein plasma levels of neuropeptide Y and catecholamines of the placental cord were measured at delivery in 40 parturient women who were divided into two groups, with 20 patients in each. NSD group underwent vaginal delivery without the presence of intrapartum fetal distress. C/S group received elective cesarean section (C/S) under spinal anesthesia. The results showed that umbilical vein level of NPY in NSD patients was significantly less than C/S patients (160.32 pg/ml vs 346.25 pg/ml, p less than 0.01). But for catecholamines levels, C/S group were significantly less than that of NSD group. PMID- 1758264 TI - [Low-flow anesthesia]. AB - Low-flow anesthesia provides benefits of ecologic advantages, reduction of pollution of operating room, increased economy and prevention of airway dessication. It is worthy to gain popularity of application. In this review article, certain aspects of low-flow anesthesia are included: 1) how to avoid hypoxemia, 2) how to prevent carbon dioxide retention, 3) how to use Lin's method in calculating the metered concentration of inhalational anesthetics during maintenance period, 4) how the time constant to affect the time to surgical level of anesthesia, and 5) the indications of low-flow anesthesia for surgery. Finally, clinical experience in low-flow anesthesia will be discussed in terms of halothane, enflurane or isoflurane with or without nitrous oxide. PMID- 1758265 TI - [The occupational hazards of anesthetic personnel]. PMID- 1758266 TI - Anesthetic management of a patient with epidermolysis bullosa. PMID- 1758267 TI - Lessons of the heart: expanding practice. PMID- 1758268 TI - Holding back: maternal readiness to give birth. PMID- 1758269 TI - Living with an irritable infant: maternal perspectives. PMID- 1758270 TI - Teaching children who are learning disabled about illness and hospitalization. PMID- 1758271 TI - Assessing postpartum fatigue. PMID- 1758272 TI - Making the most of the R.N. in a pediatric outpatient setting. PMID- 1758273 TI - Pregnancy over 35: special needs. PMID- 1758274 TI - Content analysis: steps to a more precise coding procedure. PMID- 1758275 TI - Norplant and the 'coerced conception' controversy. PMID- 1758276 TI - [The organization of medical care in enterprises]. PMID- 1758277 TI - [Methodological recommendations on the organization of centralized sterilization departments in hospitals. Appendix 1]. PMID- 1758278 TI - [The prevention of patient traumatism and asepsis in the nurse's work]. PMID- 1758279 TI - [The perinatal prevention of allergy in young infants]. PMID- 1758280 TI - [The physiotherapy of obliterating vascular diseases of the lower extremities]. PMID- 1758281 TI - [The rules of caring for hospital patients]. PMID- 1758282 TI - [The characteristics of tooth and jaw diseases in middle-aged and elderly patients]. PMID- 1758283 TI - [Rubella in adults]. PMID- 1758285 TI - [Adaptogens of plant origin]. PMID- 1758284 TI - [The basic gastroenterological diet]. PMID- 1758286 TI - [The abuse of Soviet psychiatry: facts and conjectures]. PMID- 1758287 TI - Cerebral stroke in a semi-pro football player: a case report. AB - Cervical spine trauma can clearly result in neurologic injury. An unusual traumatic event is a vascular insult of the vertebral arteries, potentially leading to stroke. The vertebral arteries are vulnerable to compression at several sites in the cervical spine. The high degree of physiologic rotation at the atlanto-axial joint places the vertebral artery at risk through normal daily activities as well as following forceful trauma, including manipulative treatment. Cerebrovascular insufficiency is an uncommon but serious complication of cervical spinal manipulation, which can lead to posterior circulatory impairment. Comprehensive diagnostic studies may be required to differentiate primary intracranial pathology from cerebral symptoms secondary to vascular compromise. PMID- 1758288 TI - Patellar location changes following EMG biofeedback or progressive resistive exercises. AB - Changes in the patellofemoral congruence (PFC) angle, the patellar rotation (PR) angle, and the sulcus angle following EMG biofeedback training that emphasized vastus medialis obliquus strengthening, the Daily Adjustable Progressive Resistive Exercise (DAPRE) technique, or no exercise were studied. Subjects were 30 normal, college females. The EMG biofeedback group and the DAPRE group followed established protocols for a 3-wk training period. The control group refrained from exercise. Patellar angles were determined with x-rays both pre- and posttest with the quadriceps relaxed and contracted. Reliability of the x rays was determined with a correlation matrix of pre- and posttest sulcus angle measurements (P less than 0.001). EMG biofeedback training resulted in significant changes in the PFC angle with the quadriceps contracted (P less than 0.05). DAPRE resulted in significant changes in the PR angle with the quadriceps contracted (P less than 0.05). The results of this study suggest that quadriceps group strength changes are not enough to fully rehabilitate patellar tracking dysfunctions. The use of EMG biofeedback training to selectively strengthen the vastus medialis obliquus appears to be essential in correcting faulty patellar tracking. PMID- 1758289 TI - The VO2max of recreational athletes before and after pregnancy. AB - This study was designed to test the hypothesis that pregnancy has an added training effect (increases "absolute" VO2max) in well-conditioned, recreational athletes. VO2max was measured serially in 20 nonpregnant recreational athletes who maintained their exercise within +/- 10% of initial levels over a 15-month period and 20 similar women who conceived and continued exercise at a reduced level during pregnancy with a return to within 20% of initial levels by 12 wk postpartum. Initially the two groups were similar in terms of age (30 +/- 1 vs 30 +/- 2 yr), weight 57.6 +/- 7.2 vs 59.7 +/- 7.5 kg), max pulse rate (189 +/- 8 vs 187 +/- 10 bpm), and absolute (3083 +/- 469 vs 3138 +/- 464 ml.min-1) VO2max. In the nonpregnant group the values obtained 15 months later were unchanged (weight = 57.8 +/- 6.6 kg, max pulse = 191 +/- 7 bpm, VO2max = 2977 +/- 397 ml.min-1) while those who conceived had a significant increase in absolute VO2max that was evident 12-20 wk postpartum and was maintained at the time of final testing 36-44 wk postpartum (3368 +/- 435 ml.min-1). Both weight (60.1 +/- 8.1 kg) and maximum pulse rate (185 +/- 12 bpm) were unchanged. These data indicate that pregnancy is followed by a small but significant increase in VO2max in recreational athletes who maintain a moderate to high level of exercise performance during and after pregnancy. PMID- 1758290 TI - Strength training does not improve lipoprotein-lipid profiles in men at risk for CHD. AB - Sixteen untrained males, age 46 +/- 11 yr (mean +/- SD), were studied to determine the effects of 20 wk of strength training on lipoprotein-lipid profiles and post-heparin lipase activities. All subjects had abnormal lipoprotein-lipid profiles and at least two other risk factors for coronary heart disease (CHD). To control for day-to-day variations in blood lipoprotein levels, baseline values were established by taking at least two blood samples on separate days from the training and control groups. The training program resulted in a 50% increase in upper body strength (P less than 0.001) and a 37% increase in lower body strength (P less than 0.001) as measured by the one repetition maximum test (1-RM). No changes in the 1-RM test were observed in the control group. There were no significant changes in VO2max (34.5 +/- 6.4 vs 36.2 +/- 7.4 ml.kg-1.min-1 or percent fat (25.4 +/- 4.2 vs 24.9 +/- 4.1%) with training. There were also no significant changes in plasma concentrations of triglyceride (193 +/- 96 vs 171 +/- 101 mg.dl-1), total cholesterol (231 +/- 22 vs 210 +/- 22 mg.dl-1), and HDL-C (35 +/- 6 vs 36 +/- 8 mg.dl-1), or LDL-C (139 +/- 16 vs 139 +/- 21 mg.dl-1). Furthermore, the activities of post-heparin lipoprotein lipase (9 +/- 4 vs 13 +/- 5 moles.ml-1.h-1) and hepatic lipase (35 +/- 10 vs 35 +/- 9 moles.ml-1.h-1) did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758291 TI - Regulation of Ca(2+)-signaling in cardiac myofilaments. AB - The contraction and relaxation of heart muscle cells is associated with a transient change in the intracellular level of free Ca2+. This transient reflects a release from the sarcoplasmic reticulum of Ca2+ ions that turn on the reaction of myosin cross-bridges of the thick filaments with actin of the thin filaments. Without this transient no contraction occurs. The first part of this paper is concerned with the molecular processes by which Ca2+ signals the actin-myosin reaction. It will show that the activation in reality involves release of the thin filaments from a prevailing inhibited state. The inhibited state depends on the activity of the troponin (TN) complex and tropomyosin (TM); disinhibition requires Ca(2+)-binding to TN. The second part of the paper describes evidence that the signaling process is itself modulated by the mechanical and chemical state of the myofilaments in the short term and by altered gene expression in the long term. PMID- 1758292 TI - Modulation of cardiac contractility by myosin light chain phosphorylation. AB - Cytosolic free [Ca2+] ([Ca2+]c) mediates primary regulation of cardiac contractility. Both the magnitude and time-course of [Ca2+]c transient that is elicited by a sarcolemmal action potential play central roles in defining the characteristics of the mechanical response that occurs during a single excitation contraction coupling cycle. Numerous modulators of cardiac contractility, both hormonal and autoregulatory, act to influence contractile function via direct effects on various cellular processes that govern [Ca2+]c dynamics. Cardiac contractility can also be influenced by mechanisms that alter the responsiveness of the contractile element to activation by Ca2+ (see preceding paper). There is growing interest in the possibility that the phosphorylation of the P-light chain subunit of cardiac myosin by a Ca(2+)-calmodulin-dependent myosin light chain kinase may modulate cardiac muscle contractility by increasing the sensitivity of the contractile element to activation by Ca2+. The types of experimental data that have led to the development of this hypothesis and the unique aspects of cardiac P-light chain phosphate content regulation will be briefly addressed in this paper. Furthermore, several unresolved issues regarding the functional significance of cardiac P-light chain phosphorylation in intact myocardium are identified. PMID- 1758293 TI - Leisure physical activity and age at menarche. AB - Early menarche has been associated with higher risk of breast cancer. A prospective study of 2487 girls, has been conducted in Quebec City, Canada, to evaluate the relationship of exercise to menarche, taking personal and family characteristics into account. Weight, height, body mass index, and abdominal and supra-iliac skinfolds were inversely associated with age of menstruation. Mother's age at menarche was positively associated with age of menstruation. Age, mother's age at menarche, and weight-adjusted incidence density ratios (IDR) showed no association between energy expenditure and onset of menstruation. Girls who participated in dance, gymnastic figure skating, synchronized swimming, or diving competitions had a lower risk of reaching menarche at an early age (IDR = 0.71 (0.51-0.97)). PMID- 1758294 TI - Potential misclassification in studies of physical activity. AB - Regular physical activity is associated with a reduced risk of coronary heart disease, although debate still occurs over the level of intensity required for cardioprotection. The use in epidemiological studies of the arbitrarily defined categories of light, moderate, and hard, as proxy measures of relative intensity has administrative merit but risks potential misclassification, particularly in women and the elderly. This potential misclassification is the result of the inappropriate categorizing of activity based upon absolute intensity values regardless of age or gender. Coronary heart disease is more common in the elderly and recent activity more important than remote for cardiac benefit. It is thus essential to resolve the issue of the level(s) of exercise intensity needed to provide health benefits. Only when this information is available will it be possible to give rational and safe public health advice. PMID- 1758295 TI - Lumbar spine loads during the lifting of extremely heavy weights. AB - The reaction moments at the knee, hip, and L4/L5 joints, and the compressive and shearing forces on L4/L5 are documented in powerlifters competing in a national powerlifting championship. Analyses were made of 13 female and 44 male competitors. The joint moments and forces were estimated from a linked segment model (WATBAK) that incorporated functional low back extensor musculature with a moment arm of 6 cm and a line action that was oriented 5 degrees posteriorly to the L4/L5 compression axis. This oblique orientation of the extensor muscles reduced the anterior shearing load on the vertebral motion unit. Average compressive loads on L4/L5 were estimated up to 17,192 N while the highest average L4/L5 and hip moments were 988 and 1047 N.m, respectively. The sumo deadlift style resulted in a 10% reduction in the joint moment and 8% reduction in the load shear force at the L4/L5 level when compared with the conventional lifting style. Formulation of linear regression equations to predict the load lifted using reaction joint moments yielded substantial unexplained variability, though significant relationships were found. This analysis suggested that there is large variability in the pattern of loading joints among national class powerlifters. PMID- 1758296 TI - Electromechanical delay during knee extensor contractions. AB - The purpose of this study was to investigate the magnitude of electromechanical delay (EMD) and its possible dependence on muscle type, type of contraction, fatigue, level of force, initial muscle length, and muscle contraction velocity. This was achieved using an experiment that measured voluntary knee extensor torques and surface EMG activity for a variety of different contractile conditions in seven male subjects. EMD values were obtained using a cross correlation technique in three experimental KIN-COM dynamometer conditions of vastus medialis, rectus femoris, and vastus lateralis. In the first condition, a series of 10 repetitive submaximal (50% and 70% MVC) isometric knee extensor contractions were performed at knee angles of 90 degrees and 130 degrees extension. In the second condition, 10 maximal isokinetic knee extensor contractions were performed during passive shortening and lengthening. As such, the dynamometer was used to passively move the knee joint at 30 degrees.s-1 and 60 degrees.s-1. Both during lengthening and shortening, the contractions occurred at an angular position of 110 degrees. In the last condition, a repetitive submaximal isometric knee extensor fatigue test was performed for 100 s (150 contractions). At 10, 40, and 90 s during the time course of this fatigue test, a series of 10 contractions were recorded. To avoid a phase lag, which is introduced with one-way filtering, the EMG was processed with a bidirectional low pass filter application. A significant main effect in EMD for the factor level of force was found. The EMD values obtained at a force level of 50% MVC were longer than at 70% MVC (107 vs 98 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758297 TI - Injuries and adherence to walk/jog and resistance training programs in the elderly. AB - To evaluate the effects of 26 wk of aerobic and resistance training on the incidence of injury and program adherence in 70- to 79-yr-old men and women, 57 healthy volunteers (25 males, 32 females) were randomly assigned to a walk/jog (W/J, N = 21), strength (STREN, N = 23), or control (CONT, N = 13) group. Walk/jog training was for 30-45 min, 3 d.wk-1 with intensity equal to 40-70% heart rate max reserve (HRmax reserve) during the first 13 wk, and 75-85% HRmax reserve for weeks 14-26. STREN training consisted of one set (10-12 repetitions) each of 10 variable resistance exercises performed to volitional fatigue. Forty nine of the original participants completed the training program. Walk/jog training increased VO2max from 22.5 to 27.1 ml.kg-1.min-1 (P less than or equal to 0.05) while STREN and CONT showed no change. STREN improved significantly in chest press and leg extension strength (P less than or equal to 0.05) while W/J and CONT showed no change. Adherence to training was 20/23 (87%) and 17/21 (81%) in STREN and W/J, respectively. One repetition maximum (1-RM) strength testing resulted in 11 injuries in the 57 subjects (19.3%) while STREN training resulted in only two injuries in 23 subjects (8.7%). Walk training during weeks 1-13 resulted in one injury in 21 subjects (4.8%). Eight of 14 subjects (57%) who began jogging intervals at week 14 incurred an injury: two of eight (25%) of the men and all of the women (6 of 6). All W/J training injuries were to the lower extremity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758298 TI - Daily variation in gastric emptying when using the double sampling technique. AB - The purpose of this study was to establish the intra-individual variation in the rate of gastric emptying (GE) by using the double sampling technique of George. Eight healthy male volunteers, all familiar with gastric intubation and testing, participated in four GE tests, using an isotonic fluid as a test meal. Conditions were kept constant during all four tests, and each test was separated by at least 48 h. The within-subjects coefficient of variation proved to be 29%. The findings demonstrate that, given standard conditions, GE is reproducible from day to day. PMID- 1758299 TI - Effect of phonophoresis on serum salicylate levels. PMID- 1758300 TI - Can we have a distinctive theory of memory? AB - The current status of the concept of distinctiveness an applied to memory research is discussed. In spite of the fact that distinctiveness is difficult to define, an increasing number of memory phenomena have been explained in terms of distinctiveness. These phenomena are grouped into four classes, which vary in how distinctiveness is operationalized. Distinctiveness has different effects on memory performance, depending on how it is defined, suggesting that the concept of distinctiveness has been overapplied. In addition, current theoretical explanations of the effects of distinctiveness on memory fail to specify what the different definitions of distinctiveness have in common, and fail to encompass adequately the broad range of phenomena to be explained. A limited theory of distinctiveness is proposed, in order to explain why conceptually incongruent material is remembered well. PMID- 1758301 TI - Problem-oriented training promotes spontaneous analogical transfer: memory oriented training promotes memory for training. AB - Spontaneous analogical transfer is the use of information from one problem to solve another problem, without an explicit hint to use the previous information. The results of five experiments were that if subjects tried to solve a training problem before hearing its solution, or tried to explain a training story's solution before hearing the correct explanation, spontaneous transfer was more likely than it was if subjects had studied the same training passage for memory before hearing its solution or explanation. The advantage of problem-oriented processing over memory-oriented processing occurred even though solution attempts nearly always failed, and the advantage was not reduced if the target problem was tested 15 min later rather than immediately after training. We propose that problem-oriented processes performed at study are appropriate processes to use at test. Further support for the account comes from subjects' memory for the training passages; the advantage for problem-oriented processing on solution tasks was mirrored by an equally substantial advantage for the memory-oriented subjects on a recall task. PMID- 1758302 TI - Mental rotation of compound stimuli: the effects of task demands, practice, and figural goodness. AB - Four experiments examined whether or not mental rotation of compound stimuli is a holistic process. Large letters (global aspect) composed of small letters (local aspect) were presented, and the format (normal vs. reflected) of each aspect was manipulated independently. In Experiment 1, the rate of mental rotation was compared under divided- and focused-attention instructions. The overall rate of mental rotation was faster under focused-attention instructions than under divided-attention instructions. Also, contrary to previous findings, in the divided-attention task, the slope of the rotation function was smaller when the stimulus configurations contained aspects with congruent formats (both aspects were normal or mirror-reversed letters) than when they contained aspects with incongruent formats (one normal and one mirror-reversed letter). This pattern of results is unlikely to be caused by the subjects' level of familiarity with the divided-attention task (Experiment 2), by postrotation processes (Experiment 3), or by stimulus attributes (figural goodness) confounded with the format congruency variable (Experiment 4). The implications of these results for models of mental rotation of compound stimuli are discussed. PMID- 1758303 TI - Phonological assembly in reading: lexical contribution leads to violation of graphophonological rules. AB - According to current models of reading, the phonological representation of a letter string could be generated by means of two different procedures. The first consists in the looking up or addressing of the phonological representation of the appropriate word in the mental lexicon. The second consists in the assignment of a phonological code to the various orthographic units that occur in the letter string and the assembly of them into a unitary phonological representation. However, the various models of phonological assembly differ in the nature of the knowledge that such assembly requires. On the one hand, dual-route theories assert that the assembly process operates by means of extralexical graphophonological rules and, therefore, without reference to lexical knowledge. On the other hand, in analogy theories and interactive models of phonological assembly, the lexical phonological representations of words orthographically close to the letter string (the orthographic neighborhood) are supposed to contribute to the translation process. The aim of the experiments reported here was to empirically distinguish between these two categories of models. In Experiment 1, subjects were asked to pronounce pseudowords containing the letter g. Results indicate that the phonological representation assigned to the letter g depends on the pronunciation favored by the lexical neighbors. Experiment 2 shows that lexical contribution to phonological assembly also takes place in lexical decision. PMID- 1758304 TI - Spacing judgments as an index of integration from context-induced relational processing: implications for the free recall of ambiguous prose passages. AB - The effect of information integration on the recall of ambiguous prose passages was investigated. In Experiment 1, subjects read ambiguous passages that were difficult to comprehend without titles. In judging the relative positions in the passages of pairs of test sentences, subjects performed better when they read passages headed by a suitable title than when they read untitled passages or received a title at the time of testing. In Experiment 2, subjects provided with a title at encoding also better discriminated complete old sentences from foils composed of fragments of two different old sentences than did subjects provided with no titles or with titles at the time of testing. These two tests index the degree of inter- and intrasentence information integration, respectively. Two findings indicated that integration affected free recall of an ambiguous passage. First, when the degree of integration of the passage's propositions was controlled, free recall of the passage was no different for subjects who did or did not know the passage's title at encoding. Second, inducing subjects to comprehend the passage's sentences individually, without relating them to one another, reduced free recall of the passage. PMID- 1758305 TI - A bias in favor of the positive response to high-frequency words in recognition memory. AB - A relatively liberal response bias for high-frequency words and a violation of the mirror effect for hit and false-alarm rates were found in a yes-no recognition-memory test. Subjects more frequently responded "old" to high frequency words than to low-frequency words. Four experiments were conducted to determine the causes of the different response biases and of the violation of the mirror effect. The word-frequency effect on hit rates did not appear, whereas the false-alarm rate for low-frequency words was lower than that for high-frequency words. When low- or high-frequency words were presented separately in distinct halves of a recognition-memory test, the relatively liberal response bias for high-frequency words was diminished. A model for recognition judgment is proposed that assumes the use of a common criterion for low- and high-frequency words. PMID- 1758306 TI - Forgetting in recognition memory with and without recollective experience. AB - Retention interval was manipulated in two recognition-memory experiments in which subjects indicated when recognizing a word whether its recognition was accompanied by some recollective experience ("remember") or whether it was recognized on the basis of familiarity without any recollective experience ("know"). Experiment 1 showed that between 10 min and 1 week, "remember" responses declined sharply from an initially higher level, whereas "know" responses remained relatively unchanged. Experiment 2 showed that between 1 week and 6 months, both kinds of responses declined at a similar, gradual rate and that despite quite low levels of performance after 6 months, both kinds of responses still gave rise to accurate discrimination between target words and lures. These findings are discussed in relationship to current ideas about multiple memory systems and processing accounts of explicit and implicit measures of retention. PMID- 1758307 TI - Investigation of osmotically stable spheroplasts from two strains of Escherichia coli ML-35, W7-M5. AB - Osmotically stable spheroplasts were produced from Escherichia coli ML-35 and W7 M5 using either 1 min exposure to polymyxin B or 10 min exposure to Tris/EDTA, followed by 1 to 3 h incubation with lysozyme. Spheroplast membrane permeability studies were conducted using paired radioactive probes with E. coli ML-35. Experiments with 14C-sucrose-16 kD 3H-dextran indicated that the outer membrane had lost its barrier to 16 kD dextran. Parallel experiments with 81 kD 3H-dextran indicated that the outer membrane was impermeable to the larger dextran. EDTA treated cells also showed outer membrane permeability to 16 kD dextran. Cytoplasmic membrane integrity was confirmed using 14C-sucrose and 3H2O before and after exposure to polymyxin B and EDTA. Scanning electron microscopy showed that a rough surface on polymyxin B produced spheroplasts while Tris/EDTA spheroplasts showed the same smooth surface as control cells. PMID- 1758308 TI - Haemagglutination inhibition antibody levels one year after natural measles infection and vaccination. AB - An assessment of haemagglutination inhibition antibody (HAI) titres of 1,163 children, comprising 739 recipients of live measles vaccines and 424 patients with natural measles infection after 1 year was made in this investigation. Statistical analysis revealed a significant difference in the levels of HAI antibodies. Of the vaccinated children a significant 67.45% showed antibody titres of less than or equal to 1:16, while only 23.48% of children with natural measles showed these antibody titres. The importance and implication of such HAI antibody titres is discussed. PMID- 1758309 TI - Effect of Cd2+ on phosphate uptake by cadmium-resistant and cadmium-sensitive Staphylococcus aureus. AB - The effect of Cd2+ on phosphate (Pi) uptake was investigated in the growing cells of Cd(2+)-resistant Staphylococcus aureus 1781OR and Cd(2+)-sensitive S. aureus 17810S. Inhibitor and ionophore studies showed that 32Pi uptake in the two strains occurred via the Pi porter down pH gradient (delta pH) generated by the respiratory chain. Cd2+ inhibited 32Pi uptake in the cadmium-sensitive strain 1781OS at all concentrations used (10 microM-1 mM). In strain 1781OR, possessing the plasmid-coded Cd2+ efflux system, 10-100 microM Cd2+ did not inhibit 32Pi uptake. Even at 1 mM Cd2+, inhibition of 32Pi uptake in strain 1781OR was reversed when the external Cd2+ was chelated with cysteine and activity of Cd2+ efflux system was restored. Cd2+ efflux induced by cysteine was energized either by membrane potential (delta psi) or by delta pH, which indicated that electrochemical gradient of protons (delta mu H+) was required for this efflux. PMID- 1758310 TI - Changes in cell envelope glycoproteins during germ-tube formation of Candida albicans. AB - Germ-tube formation by Candida albicans induced by N-acetylglucosamine resulted in the appearance of a 43 kD protein in a cell envelope fraction. The protein increased quantitatively in the cell envelope during the emergence of the germ tube and the amount in the envelope fraction reflected the efficiency of the morphogenesis. The 43 kD protein was labelled by the lactoperoxidase catalysed iodination procedure confirming a surface location for the antigen. Concanavalin A binding to the 43 kD protein demonstrated that this protein contained carbohydrate. Tunicamycin inhibited both germ-tube formation in C. albicans and the appearance of the 43 kD protein in the cell envelope fraction. Instead the presence of tunicamycin resulted in the appearance of a new protein of 39 kD molecular weight in the cell envelope which did not bind concanavalin A. Endoglycosidase H digestion of the 43 kD protein produced a 39 kD protein. Peptide mapping of the 43 kD protein from germ-tube cells and the 39 kD protein from tunicamycin-treated cells indicated that these proteins are homologous. PMID- 1758311 TI - Training young doctors: everybody's problem. PMID- 1758312 TI - The observed long-case in clinical assessment. AB - The University of Adelaide has developed a comprehensive approach to final-year clinical assessment through the use of ward ratings during student internships and the administration of an objective examination of clinical competence at the end of the year. The traditional clinical viva has been retained only to make pass-fail decisions on borderline students. Problems in making these decisions prompted a modification of the viva so that each student undertook two long cases, each being observed by a pair of examiners. Better agreement among examiners and more effective decision-making seemed to ensue. The success of this approach led to the introduction of observed long-cases into the ward setting. This move has been strongly supported by staff and students. The opportunities for remedial action during the course were regarded as particularly valuable. This approach may offer a practical alternative to more sophisticated assessment techniques, such as those involving standardized patients, without the need for additional resources. However, psychometric studies will have to be performed before the approach can be fully recommended. PMID- 1758313 TI - Parental problems influencing the academic achievement of medical students: a prospective study. AB - The 227 students offered places in the 1988 medical student intake at the University of Queensland were surveyed regarding their demographic characteristics. This was correlated with the students' subsequent performance and persistence during the first year of the medical course. Coming from a lower socioeconomic background and having family problems were both associated with either a decreased academic performance or an increased attrition rate. The results are discussed, relevant literature is reviewed and suggestions for further research are made. PMID- 1758314 TI - Changes in students' attitudes and values during medicine versus surgery clerkships. AB - A prospective study of students' attitudes and values was conducted during medicine and surgery clerkships over the first clinical year. Students who finished the surgery clerkship first were more cynical and intolerant of ambiguity than the medicine students. Surgery students also felt they lacked self confidence and had stronger feelings of being victimized. Cynicism and attitudes towards ambiguous situations improved during the medicine clerkship. Feeling victimized was strongly correlated with their problems with self-confidence, with cynicism, and a feeling of having to submit to authority figures. The findings of this study suggest that the clerkship order significantly affects the development of students' attitudes. Students also became more punitive and less confident as the first clinical year progressed. The implications of these changes in attitude on educational planning are discussed. PMID- 1758315 TI - A comparison of computer-assisted instruction and small-group teaching of cardiac auscultation to medical students. AB - Cardiac auscultation is suffering from declining interest, caused by competing diagnostic technology and inadequate training of doctors. Computer-assisted instruction (CAI) supporting graphics and digitized sound could be ideally suited for teaching and sharpening this skill. To evaluate this premise we randomized 35 third-year medical students to 3 hours of seminar teaching plus the use of audiotapes (group 1), the self-use of a MacIntosh-based CAI (group 2), or both (group 3). All students took a pre- and post-test consisting of eight pre recorded cardiac events and were also assessed for computer anxiety. Although there were no significant differences between pre- and post-tests for each group and among groups, group 1 had a 4.5% deterioration in its diagnostic score compared to the 7.2% and 3.2% improvements of groups 2 and 3 respectively. Group 2 used the CAI significantly more than group 3. We conclude that CAI is at least as effective as seminars in teaching cardiac auscultation to third-year medical students. PMID- 1758316 TI - Student characteristics as predictors of drop-out from medical school: admissions to Beer-Sheva over a decade. AB - The study sought to identify variables from the demographic, socio-economic, academic and personal background of medical students in order to reveal possible predictors of drop-out from medical school. The research included 443 students who were admitted to Ben Gurion University (BGU) Medical School during its first 10 years, 1974-1983. It was found that the permanent drop-out rate in BGU Medical School (12.6%) is relatively high and mainly due to academic failures. Of all admitted students 11.3% do not graduate on time due to academic reasons. The findings are discussed and suggestions for changes in admissions policy are provided. PMID- 1758317 TI - The construction of a 'topic tree': a way of familiarizing a teaching staff to problem-oriented learning in a master's programme in public health. AB - At the planning stage of a community-oriented and problem-based learning master's programme in public health it is indispensable to build a network of teachers, experts in specific fields, willing to guide the students in acquiring new competencies and ready to facilitate the experimental learning process. We discuss in this paper the construction and the utilisation of the 'topic tree'. In addition we show how the teaching staff get acquainted with that educational methodology by experimenting with it themselves (prior to the students). About 10 experts, each one a specialist in a given field, have conceptualized their approach in building a topic tree (concept tree); such a tree makes it possible to schematize the topics to be understood in order to solve a given problem and the relationship existing between actions to be undertaken. The experiment, meant to initiate the teaching staff in experimental learning procedures, was appreciated by all the experts, who considered it a creative and stimulating method. It also permitted the construction of a bibliography including key documents concerning each identified priority health problem. We discuss the utility and the relevance of our approach in the perspective of initiating teachers in experiential learning based on problem-solving. PMID- 1758318 TI - Continuing medical education and career choice among graduates of problem-based and traditional curricula. AB - A survey was conducted among graduates of two Canadian medical schools who have been in practice for more than 9 years. The purpose of the study was to test the hypothesis that graduates of a problem-based curriculum differ from graduates of a traditional curriculum in their attitude to and participation in continuing medical education (CME) activities. Differences were noted in the rate of participation in certain CME activities (attendance at national and international conferences and meetings) between specialists and family doctors in both groups of alumni. However, the data indicate that the differences in learning-teaching methods employed in the course of the undergraduate medical curriculum do not exert a decisive influence upon the learning habits of the graduates. PMID- 1758319 TI - Student-directed problem-based learning in general practice and public health medicine. AB - The development and implementation are described of a new 6-week course in general practice and public health medicine for final-year medical students. This course is based on the principles of student-directed problem-based learning in small groups and makes substantial use of student attachments to local general practices which act as learning resources. Student assessment is by profiles. Course evaluation is by qualitative feedback, and the results of this are presented. The course offers a flexible learning environment in which the aims of its designers and the goals of their students can be achieved. PMID- 1758320 TI - Profile of doctors who participate in continuing medical education in Malaysia. AB - A random survey of 400 doctors was carried out over a period of 3 months to determine the factors that would facilitate or inhibit the participation of doctors in continuing medical education (CME) in Malaysia. Regular participation in CME was defined as participation in any activity (self-directed reading or attending organized activities) at least once a month during the past year. It was found that 78% of doctors regularly participated in CME. Working in a hospital environment and being members of the Malaysian Medical Association and at least one specialty organization appeared to be important facilitatory factors in CME participation. These doctors also read the local medical journals regularly and subscribed to other journals. In addition, they were more likely to possess postgraduate qualifications and would have teaching, research, diagnostic or clinical responsibilities as major components of their work. They were more likely to practise in the big cities and would tend to be active in at least one voluntary or social organization. If they were in the Government sector, they were more likely to work in the Universities or in the Hospital Division of the Ministry of Health. The 22% who were less likely to participate in CME were general practitioners in the private sector. They worked long hours with day, evening and/or night shifts every day. If the doctors were in the Government sector, they were more likely to be in the Health Division, working in administration and public health, or they were in the armed forces and other organizations such as local councils. They worked in the smaller towns or in the districts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758321 TI - Clinical information in psychiatric practice: what do doctors know, what do they think is known and what do they record? AB - Deficiencies in recording clinical information are a widespread problem in both psychiatry and medicine. Previous studies have not established whether information not recorded in the notes is nonetheless known to clinicians. This study compared both the information known to individual clinicians and that recorded in the notes with previously established criteria. Overall, individual clinicians recalled more information than was recorded in the notes (median values: clinicians 47-63% of criteria; notes 42%) and when all this individual knowledge was pooled, 88% of the preset criteria were satisfied. Consultants, but not more junior staff, recalled significantly more about subsections of the history which they considered to be especially relevant to the management plan for a given patient. Only a third of data not known to clinicians, but thought by them to be recorded in the notes, was actually present. The implications of these findings for clinical audit and medical education are discussed. PMID- 1758322 TI - Training general practitioners to teach psychiatric interviewing skills: an evaluation of group training. AB - Group teaching in problem-based interviewing based on video and audiotape feedback of the doctor's own consultations significantly improved the ability of experienced general practitioners to teach psychiatric skills to their trainees. When the GPs were randomly allocated to one of three further training experiences -video feedback of their tutorial sessions, discussion about how to teach and no further teaching, there were very few differences between the groups. The greatest impact on improving teaching skills was brought about by watching their own consultations in a group feedback setting. PMID- 1758324 TI - Postgraduate medical examinations. PMID- 1758323 TI - Proposed changes in medical education in Czechoslovakia. PMID- 1758325 TI - Permanent Working Group of European Junior Hospital Doctors. Policy statement on postgraduate medical education in general practice. Prepared by the Subcommittee on Postgraduate Medical Training. AB - The Permanent Working Group of European Junior Hospital Doctors' Policy Statement on Postgraduate Medical Education reviewed the regulations governing postgraduate training in the European Communities and set out educational principles which the Group believed were applicable in all medical disciplines. Recognizing that the training of general practitioners poses some specific problems, the PWG has adopted this further statement on training in general practice. It reaffirms the need for trainees to have a model of good practice, extensive experience, theoretical teaching, critical scrutiny and regular, unambiguous feedback regarding progress. In addition, it argues for the availability of an appropriate number of posts for GP trainees both in hospitals and in practices and an awareness among hospital-based trainers of the educational needs of trainees who intend a career in general practice. PMID- 1758326 TI - Approaches to learning of students in an Indonesian medical school. AB - This paper reports on a study of approaches to learning of undergraduate medical students in the University of Gadjah Mada, Indonesia. The Lancaster Approaches to Studying Inventory was translated into Indonesian and the translated form pilot tested. The instrument was then completed by 90 students, 30 each in first, second and fifth year in the Faculty of Medicine. It was found that Indonesian students generally gave higher rates than previous studies have reported. Factor analysis of their responses showed strong resemblances to other groups in the factors of meaning and reproducing orientation. Differences found in Indonesian students' responses were in strategic and non-academic orientations. There were differences between the response patterns of first-, third- and fifth-year students. It is concluded that the instrument is valid for use in Indonesia. PMID- 1758327 TI - Complementary value of traditional bedside teaching and structured clinical teaching in introductory surgical studies. AB - A prospective randomized trial was conducted to see if student performance in a combined multiple choice and objective structured clinical examination was better following a period of structured clinical teaching compared with traditional bedside teaching. Student groups were crossed over in a second phase of the experiment to allow the two teaching techniques to be compared sequentially in the same group. There was no significant difference between the two teaching techniques as measured by performance in a criterion-referenced examination. The results of the study led to modification of the curriculum for third-year introductory surgical studies to incorporate both teaching strategies, which are regarded as complementary in value. PMID- 1758328 TI - Self-assessment and learning through GOSCE (group objective structured clinical examination). AB - The objective structured clinical examination (OSCE) was modified to serve as a means of self-assessment and learning, rather than as an examination. The main modifications were to adapt it for use by small groups instead of individuals, and to provide a correct answer or other feedback at each station. The resulting group OSCE (GOSCE) was used as an introductory session in two residential refresher courses for general practitioners. The 300 participants rated it highly as a method of self-assessment and as an enjoyable social event. Four potential applications of the GOSCE are suggested: as an assessment instrument for formative and informal summative assessment, as a resource for learning about interpersonal and interprofessional relationships, and as a framework for problem based short courses. PMID- 1758329 TI - The cognitive context of examinations in psychiatry using Bloom's taxonomy. AB - Psychiatric practice involves complex thinking patterns. In addition to commanding a huge number of facts, the student must learn to manipulate factual knowledge to solve diagnostic problems, develop treatment plans, and critically evaluate those plans. This study demonstrates an empirical method for evaluating the level of cognitive processes tested in multiple choice examinations. Use of Bloom's taxonomy in evaluating test items demonstrated the majority of test items on a psychiatry clerkship examination and a resident in-training examination fell into the most basic cognitive level, that of simple recall. The utility of Bloom's taxonomy is discussed along with implications for medical education. PMID- 1758330 TI - Supervised role-play in the teaching of the process of consultation. AB - Supervised role-play is presented as a method for teaching the process of the medical consultation. The process of the consultation is reviewed and a brief description of supervised role-play is given with some of its advantages and disadvantages. Some simple devices used in the method are explained with examples. The 'living' nature of the consultation is emphasized and an active method of teaching is advocated. PMID- 1758331 TI - Death, dying and the medical student. AB - The objective of this study was to determine the extent of medical students' experience of death and dying. A questionnaire was given to two groups of Birmingham medical students at the beginning of clinical studies (third year) and in the final year which was designed to estimate their experience of death and of dying people. The questionnaire also explored the students' attitudes to their own future deaths. Questionnaires were returned by 119 third-year and 143 final year students. Students had little experience of death and what they did have was largely acquired before entry to medical school or in their social rather than medical lives. Where they did have experience of death this was often traumatic and there was little chance for them to have counselling about it. There is need for increased teaching about death and dying particularly before clinical training and at the time of graduation. Another time may be at the beginning of human dissection. PMID- 1758332 TI - Study approaches of nursing students: effects of an extended clinical context. AB - In the first part of this study a comparison is made between the approaches to studying adopted by failing and achieving nursing college students. It is concluded that failing students manifest approaches to studying that are, in some respects, conceptually difficult to interpret. This conclusion is presented against a background of similar findings that have emanated from other recent studies on student learning. The second part of this study investigates the influence of contextual perceptions on the manifestation of the approaches to studying adopted by achieving students. In thus exploring the manifestation of different forms of contextualized approaches to studying (which are referred to as study orchestrations) a distinction is made between the influences attributable to 'conventional' and 'clinical' sets of contextual variables. In an extension of previously reported studies, it is concluded that the combined set of these contextual variables explains significantly more of the variation in study approaches than the set of 'conventional' variables. It is further concluded that, under the influence of an extended set of contextual variables, conceptually related, but differing forms, of study orchestration may be manifested; a general form which is readily interpretable in terms associated with 'conventional' academic contextual variables and a clinical form which, in the present study, is associated specifically with a nursing academic environment. The implications of these conclusions for nursing education are discussed and areas for future research are indicated. PMID- 1758333 TI - Effects of communication skills training on students' diagnostic efficiency. AB - This study evaluates the impact of a training programme in communications skills on subsequent diagnostic efficiency. Videotaped history-taking interviews conducted by groups of specially trained and control groups of students were rated for their diagnostic efficiency by two medical practitioners. Students in the trained group had shown greatly increased skills in interviewing and interpersonal effectiveness as a result of their training. A comparison of ratings given by the two experimentally naive, independent observers revealed that trained students were significantly better at eliciting full, relevant data from patients--they were diagnostically more efficient, but took no longer than their control group counterparts to elicit the information. Further research with the medical interview rating scale will clarify the skills required of medical students in interviewing and diagnosis and facilitate remedial training for students who show poor interview skills. PMID- 1758334 TI - Developmental accounts of the transition from medical student to doctor: some problems and suggestions. AB - This paper is concerned with the difficulties in integrating the results of recent cognitive research on expert-novice in clinical reasoning. The focus is on the issue of stage theories as a means of achieving such integration. Objections to the use of such theories in developmental psychology are reviewed. In light of these objections, it is argued that it is important to distinguish between stage theories and stage-like phenomena. It is concluded that a stage theory is not likely to provide adequate integration. Some alternative explanations, which include both cognitive and non-cognitive factors, are discussed. PMID- 1758335 TI - Awareness of drug costs among general practitioner trainees. PMID- 1758336 TI - Non-cognitive components in the selection and training of medical students. PMID- 1758337 TI - Problem-based learning and community-oriented medical education. PMID- 1758338 TI - Content validity of objectified tests. PMID- 1758339 TI - [How to identify an aspecific association? Epidemiological considerations on the study of health of office workers]. AB - An epidemiological approach to the study of health conditions of office workers. Nowadays the work-relatedness of the majority of diseases occurring at the workplace is by no means obvious. The relationship to work environment and performance of work is one of several causative factors. However, the multifactorial origin of diseases is not at all a new concept since principles and methods for the study of the numerous factors playing a role in any association between exposure and disease are already available. The model of causal constellations developed by Rothman can be particularly useful for the investigation of "non-specific" associations, like those commonly occurring in office work. The study of the health conditions of office workers is faced with many difficulties, including the identification, measurement and classification of exposure variables and health outcomes. In designing these studies, particular attention should be devoted to aspects regarding sample size, length of observation and referent population. PMID- 1758340 TI - [Health risks for waste disposal industry workers]. AB - Waste disposal currently constitutes a major public health problem in Italy and other industrialized countries. In view of the increasing volume of waste accumulated and disposed of without control, there is now an ever pressing need for regulated disposal that involves minimum risk for the environment and the community. Hence a new industrial sector has emerged that is highly specialized and varied, on account of the wide field of activity and technology, from collection and storage of refuse, processing and definitive disposal, to reclamation and improvement of illegal dumps. The industrial waste sector has not been fully developed and it is currently believed that most disposal is performed without sanitary control. Little attention has been given to the environmental impact of these operations and similarly little is known of the possible health effects for the operators. Acquisition of toxicological and health data is therefore essential to establish correct and appropriate regulations for the development of this industrial sector. An objective risk evaluation will require filling in many information gaps, which are partly the results of a natural uncertainty surrounding any innovative process, but are above all due to the vastness of the problem that is not easily defined in concrete terms as regards types of waste and number of operators involved. PMID- 1758341 TI - [Problems and perspectives of occupational carcinogenesis]. AB - Epidemiologic research has played an important role in identifying and confirming the carcinogenicity of chemicals. This was facilitated in the past by the high levels of exposure and by the simple correspondence between one exposure and one or few job titles. Today we are faced with a different picture: workers are exposed to complex mixtures, exposure levels have decreased while mobility of the work-force has increased. In this changing context, epidemiology needs new methodological tools to improve the validity of risk assessment. The most promising of these seem to be the new techniques of biochemical epidemiology and the development of job-exposure matrices. Among the more traditional tools, record-linkage studies may be relevant in identifying long-term occupational hazards. The methodological problems and the ethical and operative implications of these trends in research are discussed. PMID- 1758342 TI - Blood lead and erythrocyte protoporphyrin levels in the general population of an area in southern Italy. AB - Seven hundred and twenty subjects not occupationally exposed to lead were examined, among blood donors from a Bari hospital. Short case-histories were taken including personal data, residence, occupation, habits. The parameters considered were blood lead and protoporphyrin levels. The mean values found in Bari were respectively, 8.4 micrograms/100 ml, S.D. = 4.5 and 11.3 micrograms/100 ml, S.D. = 10.9. The results show that, at present, reference values for blood lead levels in the population are lower than the limits set by D.P.R. No. 496/82 which incorporates EEC directive No. 77/312 concerning biological monitoring of lead exposed populations. PMID- 1758343 TI - [Degenerative changes in the coxofemoral articulation due to occupational causes. I. Radiological description of a control population]. AB - With a view to initiating epidemiological studies aimed at demonstrating the causal or concausal role of certain working activities in degenerative diseases of the coxo-femoral articulations, the authors report data from a radiological study of a reference population and the necessary conditions for their correct use. Statistical analysis of the descriptive features leads to some interesting observations on the evolution with age of the radiological picture of the coxo femoral joints (and on the aging of these joints). There was an increase with advancing age of some of the alterations that are characteristic of degenerative articular processes, such as sclerosis and osteophytosis. Reduction of articular "rima", however, occurs suddenly between the ages of 36 and 45 and does not seem to subsequently undergo any statistically significant evolution. PMID- 1758344 TI - [Sensitivity, precision and resolution of the optical microscope in the study of environmental pollution by asbestos fibers]. AB - The authors comment on the methods and equipment used in two Italian laboratories for sampling and microscopic phase contrast analysis of asbestos and other respirable fibres in the air of the general environment, i.e., the Dust Analysis Laboratory, Industrial Hygiene and Toxicology Department of the Institute of Occupational Health (Clinica del Lavoro), University of Milan and the Technical Microscopy Laboratory, Ground Resources and Land Control (Georisorse e Territorio) Department of Turin Polytechnic, which use identical methods. Airborne dust samples are taken with personal samplers, 1 l/min air flow (sample duration 4-8 h), filtering air on 25 mm diameter, 0.8 micropore cellulose filters (about 300 mm total net surface of dust deposit). The following equipment is used for counting and analysis of fibres: a) Clinica del Lavoro, Milan: Polyvar Reichert-Jung microscope, 500 magnitudes, Zernike positive phase contrast; numerical counting on 100 whole ocular fields, equal to 6.38% of the total net surface of dust deposit on the membrane; b) Turin Polytechnic: Leitz Ortholux microscope, 500 magnitudes, Heine and Zernike phase contrast with mean standard contrast; numerical counting on square grid, with explored surface total equal to 1.68% of the total net surface of dust deposit on the membrane. Measurements performed: Clinica del Lavoro, Milan: 2,980 since 1960; Turin Polytechnic: 875 since 1965. The sensitivity of the methods for counting airborne fibres is discussed, concluding that the methods used by the two laboratories have a sensitivity between 0.05 and 1.6 fibre/litre of air, according to the overall dustiness of the environment under study. Analysis of the accuracy of the optic determinations, based on the repeated counts, shows a repeatability of 0.4 (40%) within 95% confidence limits. A resolution power of 0.35 microns is reported; however, the possibility exists (and is normally achieved in analytical practice in both laboratories) of identifying and counting fibrous elements up to 0.1-0.3 microns in diameter; this is possible in particular conditions, i.e., when there is a marked difference between the "mean" refraction index of the fibres and that of the diaphanizing liquid. For qualitative determinations of the various types of asbestos, however, analyses are limited to diameters greater than 0.5-0.8 microns, since it is necessary to be able to assess optical properties (refraction indices, basically). In the concluding discussion, comments and bibliographic references are also given concerning the comparisons with possibilities of studying fibrous particulate matter via electron microscopy. PMID- 1758345 TI - [Psychosocial factors and myocardial infarct]. PMID- 1758346 TI - 'The creation of unimaginably large amounts of radioactivity'. PMID- 1758347 TI - The medical effects of postulated accidental release of radioactive material from Heysham Nuclear Power Station. AB - The effects of a postulated reactor accident at one of the four AGRs at Heysham, NW England, have been studied, assuming a 10% release of the radioactive core. Methods used are a computer program TIRION, analysis of the radiation doses from the Chernobyl release of 1986 and the Windscale fire of 1957. Fatal cases predicted are 200 on-site, 3000 within 30 km and 250,000 in the cloud paths over Northern England. The results would suggest the incidence of fatal cancer would increase from roughly 20% to 27% in the postulated exposed population of 3.6 million. PMID- 1758349 TI - The effect of war on personal aggression. AB - The effect of war on the suicide rate and on the relative likelihood of suicide as a proportion of total personal aggression was examined in the United States for the time period from 1933 to 1986. Once unemployment was controlled for, no effect of war was detected. PMID- 1758348 TI - Chernobyl, four years on. AB - It is still too soon to make a full assessment of the Chernobyl disaster, but one should be begun, and practical inferences, with particular reference to the prevention of radiation-induced cancers, may be drawn. PMID- 1758350 TI - Iraq-occupied Kuwait: the health care situation. Conclusions. Physicians for human rights (Denmark and USA). PMID- 1758351 TI - [Treatment in the rupture of suppurating hepatic echinococcosis into the abdominal cavity]. AB - The rational surgical methods of treatment in 85 patients with suppurative hepatic echinococcosis penetrating into the abdomen cavity are presented. The own author's techniques strictly individualized in each case are described in details. The classification of the variants of the complications and their clinical features are given. The advantage of the presented surgical methods has been proved by a reduction in the period of treatment, the number of intraabdominal complications and mortality rate. PMID- 1758352 TI - [The clinico-epidemiological characteristics of opisthorchiasis foci in the Yamalo-Nenets Autonomous Okrug and the treatment results with praziquantel]. AB - A clinical and epidemiological study of opisthorchiasis foci in the Yamalo-Nenets Autonomous Okrug was carried out. 764 people were surveyed, including 473 aborigines of the north, 207 denizens, and 84 migrants. Opisthorchiasis infection rate in villages was 40.5-45.7%. The intensity of infection was lower than 200 eggs per g faeces. The modelling of opisthorchiasis prevalence performed after Muench showed the highest correlation with the "simple" and "reversible" models. Factors determining the infection spread and limiting its intensity and those influencing the effect of chemotherapy were defined. Theoretically determined radical suppressive low-dose praziquantel chemotherapy was carried out. The efficacy of the drug, 25, 30, 40 and 50 mg/kg, varied from 76.5 to 92.0% (mean 88.1%), and the decrease of the egg density was more than 60%. The incidence of side effects of the therapy averaged 45.3%. PMID- 1758353 TI - [The function of the hypophyseal-thyroid system in chronic opisthorchiasis and its combination with the Salmonella typhi carrier state]. AB - The hormonal function of the hypophysis and thyroid (TTG, T3, T4) and its dependence on hepatobiliary function, examined by hepatobiliscintigraphy, were studied by radioimmunoassay in 71 patients with chronic opisthorchiasis and in 18 chronic carriers of Salmonella typhi. in both groups. The decrease of T3 and T4 in the presence of normal TTG level was found. The imbalance of thyroid hormones activity is likely to be associated with hepatobiliary dysfunction. In chronic opisthorchiasis the hormonal disturbance may be one of the factors favouring the S. typhi carriership. PMID- 1758354 TI - [The interferon status in helminthiases. 3. Opisthorchiasis]. AB - In 23 patients with Opisthorchis felineus infection, 4 in subacute and 19 in chronic stages of the disease (7 subclinical, 8 with cholepathy and 4 with gastroduodenitis) the blood levels of alpha-interferon (IF-alpha) and IF-gamma were measured using vesical stomatitis virus culture. In patients with subacute opisthorchiasis the blood contents of IF-alpha and IF-gamma were the same as in control-30 practically healthy people (640-1280, log2 9.73 +/- 0.19, and 128-256, log2 7.75 +/- 0.25 against 640-1280, log2 10.04 +/- 0.12 and 128-256, log2 7.47 +/- 0.13 respectively). In patients with chronic opisthorchiasis the levels of IF alpha and IF-gamma were lower than in control (320-640, log2 8.68 +/- 0.28 and 32 128, log2 6.0 +/- 0.58, p less than 0.01 and p less than 0.01 respectively). Among the ones with the subclinical course of the infection the content of IF alpha was lower than in control (320-1280, log2 9.31 +/- 0.27, p less than 0.05). Patients with cholepathy had lower levels of IF-alpha and IF-gamma than those with subclinical course of the infection (160-640, log2 8.55 +/- 0.24 and 16-64, log2 5.0 +/- 0.26, p less than 0.01, p less than 0.01 respectively). That seemed to be a sign of immunodepression in the chronic stage of the disease some way more prominent in cases with cholepathy. Immediately after praziquantel therapy interferon levels remained unchanged. PMID- 1758355 TI - [Heterologous immunity in opisthorchiasis at different stages of the development of the invasion (experimental research)]. PMID- 1758356 TI - [The pathogenesis of stomach and duodenal involvement in chronic opisthorchiasis. 1. The urease test]. AB - The study using the urease test on mucous biopsies from the antral gastric part and from the duodenum of patients with chronic opisthorchiasis with endoscopic evidence of antral gastritis and gastroduodenitis, and from noninvaded patients with gastritis and duodenitis, some of them with the gastric or duodenal ulcers showed that the test was positive. The test was negative in both groups of patients when the mucosa of the gastric body was examined as well as in those without gastroduodenal pathology. It is supposed that in the both groups of patients gastroduodenal pathology was provoked by the colonization of the gastric and duodenal mucosa by gastric campylobacteria. PMID- 1758357 TI - [The characteristics of gastroduodenal pathology in patients with chronic opisthorchiasis as a criterion for the clinical diagnosis of the invasion]. AB - Using a syndrome approach the clinical pattern has been studied in 269 patients with chronic gastritis and duodenitis. 55 of patients had gastric ulcer, 105 patients had duodenal ulcer. In 130 patients chronic opisthorchiasis was diagnosed 8.9 +/- 1.9 years after the disease onset. The following syndromes are believed to be diagnostically valuable, enabling one to suspect chronic opisthorchiasis in patients with gastroduodenal pathology from the endemic foci: "low eosinophilia syndrome", "right hypochondrium" syndrome, "fever and enterocolitic syndrome" with the special consideration of the nature of dysbacteriosis of the small bowel. PMID- 1758358 TI - [A combined method for the laboratory diagnosis of opisthorchiasis]. AB - A combined method of coproovoscopy using potassium iodide (density 1.71) or zinc chloride (1.78) solutions is used for the diagnosis of opisthorchiasis in man, dogs and cats. The method is also useful for diagnosing ascaridiasis, ankylostomiasis, trichocephaliasis, and taeniasis. PMID- 1758359 TI - [Population migration and the epidemic process in opisthorchiasis]. AB - A correlation between opisthorchiasis epidemic process and population migration is reviewed at the third stage of the migration process (the formation of the migration flow, resettlement as such, and settlement of migrants in a new place) in view of the prevention of infection in conditions of the population migration. The endemic situation in the areas between which there is population migration is considered as the initial point. A simplified method for the calculation of the number of infected persons among the migrants from the endemic territories is described. PMID- 1758360 TI - [The significance of parasitic diseases in human pathology]. PMID- 1758361 TI - [An electron microscopic study of the cuticle, hypodermis and somatic musculature of the nematode Trichocephalus muris after exposure to anthelmintic preparations]. PMID- 1758362 TI - [The clinico-immunological characteristics and treatment of ankylostomiasis patients from tropical countries]. PMID- 1758363 TI - [Morphological changes in the mucosa of the stomach and the small intestine of rats under the action of mebendazole]. AB - The effect of mebendazole on the gastric and intestinal mucosa was studied in 52 intact white rats. It was shown that the drug caused a significant damage to the mucosa, especially of goblet cells of villi and crypts and interfere with the mucoid secretion. The alterations after mebendazole administration were more severe than those caused by naphthamon. On the 13-15th day after the treatment the complete restoration of the damage was not seen. PMID- 1758365 TI - [The effect of toluene and ammonia on the invasive process and immunological indices in experimental trichinelliasis in mice]. AB - Rap mice were exposed to toluene (T) inhalation for 10 days before invasion with 20 Trichinella spiralis larvae per g body weight (moderate infection). This resulted in diminished number of intestinal parasites in the presence of greater number of mast cells in the peritoneal exudate, higher IgE production, enhanced cell adhesion to trichinella larvae and of migration of splenic lymphocytes. Simultaneous inhalation of T and ammonia diminished the immune stimulating effect of the former. The number of intestinal trichinella was 1.5 times more but still twice less than in controls. Inhalation of T during the first 10 days of infection stimulated the immune response only in mice given 5 larvae per g. In those given 20 or 60 larvae per g, the immune response was suppressed and 40 and 100% of mice perished respectively. The exposure to T during 30-39 days of infection of mice given 35 larvae per g (the intensive infection) resulted in 50% death of the animals without significant changes in immune response. Simultaneous therapy with mebendazole (75 mg/kg) provided 100% survival in the presence of suppressed immune response. 100% of mice of the same group not exposed to T but treated with mebendazole died. The toxic and immunomodulating effects of T differ in intact and infected mice due to the dense, the stage of infection and to chemotherapy. PMID- 1758364 TI - [A comparative study of the efficacy of Vermox, albendazole and medamine in an experimental model of trichocephaliasis in mice]. AB - A comparison of the efficacy of albendazole, medamine, and Vermox using an experimental model of Trichocephalus muris in DBA-2 mice showed that Vermox was most effective at all stages of the parasite development. The therapeutic activity of albendazole and medamine depends on daily dose, its dividing through the day and the duration of the treatment. At larval stages of T. muris complete recovery might be achieved using a daily dose of 25 mg/kg for albendazole and 150 mg/kg for medamine, but at the adult stage the doses of the drugs should be 3-4 times higher to achieve 100% effect. The resistance of T. muris to the drugs especially increases at the beginning of egg production. PMID- 1758366 TI - [The anticestodal activity of preparations made from the breadfruit]. AB - Breadfruit tree (Artocarpus tonkinensis) is used in Laotian folk medicine for the treatment of taeniasis. Breadfruit tree preparations impair in vitro the motility of the cestodes Hymenolepis nana causing their motor excitation, contracture and death. The latter is observed when fairly high concentrations of the preparations (10(-2) = 2.10(-3)) are used. In mice experimentally invaded by H. nana it was shown that the water extraction of breadfruit tree substance is rather less effective than its ethanol extraction and has some purgative action, which increases the therapeutic effect. PMID- 1758367 TI - [The search for new antiparasitic agents. 7. A study of the relationship between the structure and the anthelmintic activity of new halogen-containing benzamides]. AB - Anthelminthic properties of new series of haloid-containing benzamides have been studied. The anthelminthic activity-structure relationships of the compounds under study has been examined. A number of highly active compounds promising for further investigations have been identified. PMID- 1758368 TI - [The search for new antiparasitic agents. 8. The synthesis and study of the acute toxicity, anti-alveolar hydatid and antihymenolepiasis activity of 1-alkyl-4[4 (heterylamino)phenyl]piperazines]. AB - The synthesis and the acute toxicity and anticestodal activity of l-alkyl-4-[ (heterylamino)phenyl]-piperazines are presented. These compounds were found to be able to suppress the growth of larvocysts of Echinococcus multilocularis in cotton rats when injected intraperitoneally in a single dose of 0.25 g/kg, close to capacity of mebendazole. The tested compounds were also highly effective against the adult stage of Hymenolepis nana. Experimentally infected mice given an oral single dose of 0.2-0.5 g/kg of the drug were radically cured. PMID- 1758369 TI - [The assessment of the clinical status of patients with alveolar hydatid disease by using statistical processing methods. 2. The correlation of laboratory tests at different disease stages and their clinical interpretation]. AB - In 44 patients with alveolar echinococcosis, the correlation between the results of main laboratory tests were studied and their clinical interpretation was given. It was shown that at an uncomplicated stage of the disease, the immune response suppressing the helminth growth plays the main role; at the stage of complications the pathogenetic significance of non-specific inflammatory responses caused by destructive processes increases; at a stage of decompensation the correlation reflects severe immunological abnormalities and progressive immunodepression. The obtained correlations might be used as a measure for determining the stage of the disease in the algorithmic method for the classification of alveolar echinococcosis. PMID- 1758370 TI - [Alpha-1-acid glycoprotein in differential diagnosis of rheumatic diseases]. AB - In recent years, the investigation of acute-phase proteins with the aid of affinity electrophoresis employing lectins as carrier substance, has become ever more important, in particular in the diagnosis of inflammatory rheumatic diseases. In order to investigate the usefulness of a determination of alpha-1 glycoprotein microheterogeneity in the sera as a diagnostic parameter, we evaluated, on a prospective basis, the sera of 85 consecutive patients presenting at our department with various inflammatory rheumatic diseases (chronic rheumatoid arthritis [RA] [n = 22], seronegative spondarthropathies [SpA] [n = 15], polymyalgia rheumatica [PMR] [n = 10], polymyositis dermatomyositis [PM/DM] [n = 8], osteoarthritis [n = 18], and infectious diseases [n = 12]). The results were expressed as reactivity coefficient of the alpha-1 acid glycoproteins (AGP/RC). A significant increase in the AGP/RC was observed in patients with various infections, and in those with RA or SpA with intercurrent infection, as compared with patients with RA or SpA with no intercurrent infection, or in healthy controls. It also proved possible to differentiate between PM/DM and PMR. Determination of the erythrocyte sedimentation rate, and quantification of the C reactive protein and of alpha-1 glycoprotein, permitted no discrimination between an increase in inflammatory activity related to the basic disease, and an intercurrent bacterial infection. The results show that the determination of qualitative changes in the acute phase proteins, in particular alpha-1 acid glycoproteins, may make it possible to differentiate between inflammatory and infectious diseases. This examination technique may be of future clinical importance. PMID- 1758371 TI - [Idiopathic hemochromatosis: association with antigens of the HLA system]. AB - HLA-A3 and HLA-B7 antigens were detected significantly more frequently in a group of 59 patients with idiopathic hemochromatosis than in a general population. The haplotype most commonly associated with the disease was A3B7. No differences in disease severity were to be found between homozygotic and heterozygotic carriers of this haplotype and patients with other haplotypes. An increased prevalence was also found for the HLA-A9 antigen. The haplotypes A9B7 and A9B27 were significantly more common among the patients investigated than among the general population. PMID- 1758372 TI - [Fluconazole in therapy of candidiasis of the oropharyngeal space in patients with HIV infection. Results of an open multicenter study of assessing the effectiveness and tolerance of fluconazole]. AB - 50 HIV-positive patients (CDC stage III to VI) with oral candidiasis proven by culture and typical clinical findings were treated with fluconazole (50 to 100 mg/day) over a period of eight to 22 days. After completion of treatment, clinical signs of oral candidiasis had disappeared in 45/50 patients. In 10/50 patients, however, increased concentrations of candida both in pharyngeal washes (greater than 10(2) PFU/ml) and throat swabs (greater than 20 colonies/culture) persisted. Four weeks later, clinical candidiasis had reappeared in 22/42 patients and another 14/42 patients without clinical symptoms had pathological concentrations of candida in culture. In no case did treatment with fluconazole itself have to be aborted because of adverse reactions. Most of the patients had multiple concomitant bacterial and/or viral infections requiring comprehensive medication. The side effects observed (nausea, headache, changes in the blood picture, etc.) were due to the concomitant infections and their specific therapy. PMID- 1758373 TI - [Experiences with a modified implantation technique of Port-A-Cath systems as continuous venous access in infants and children]. AB - Since April 1987 we implanted the Port-A-Cath infusion system in 60 children in the age of 2 months to 16 years (median: 4.3 years). We only used the adult system (Pharmacia). By one right side infraclavicular incision the silicon catheter was implanted into the jugular vein and also the port was fixed on the pectoral fascia. We saw one severe complication as a port perforation through the skin. 1.6% was the very low rate of complications which appeared in the median of the port using time of 168.5 days. PMID- 1758374 TI - [Jaundice and pancreatitis in a 50-year-old patient (Leptospirosis icterohaemorrhagica)]. PMID- 1758375 TI - [Differential therapy with oral antidiabetic drugs]. PMID- 1758376 TI - [Acute septic cardiomyopathy: a manifestation in multi-organ failure in infection?]. PMID- 1758377 TI - [Focal liver changes in the sonogram. Recommendations for further diagnosis]. PMID- 1758378 TI - [Fibromyalgia syndrome with IgA and IgG subclass deficiency]. PMID- 1758379 TI - [Integrated psychosomatic medicine]. PMID- 1758380 TI - [Pentamidine protecting from the complications of AIDS]. PMID- 1758381 TI - [Recent findings on infantile autism]. PMID- 1758382 TI - [Effect of pre-treatment with pyridostigmine on the stimulation of growth hormone by clonidine and GRF]. AB - The large availability of biosynthetic GH suggested the need to define the more accurate way to make diagnosis of GH deficit. Only one stimulation test by clonidine or insulin is not enough to define a GH deficit, and this because often it's possible to get "false negative" tests. The GH is regulated by the influence of GRF and somatostatin that respectively are under the adrenergic and cholinergic control, for this reason we studied how and in which measure a cholinergic agonist (pyridostigmine) acts on GH release during the clonidine and GRF stimulation tests. We studied the area under the curve (AUC), the peak and the mean of the value of GH after clonidine or clonidine and pyridostigmine, and after GRF or GRF and pyridostigmine: we got the following results: 191 +/- 71.33 (AUC), 5.42 +/- 1.68 (peak), 2.44 +/- 0.54 (mean) after clonidine stimulation test; 1048 +/- 442.37 (AUC), 19.5 +/- 10.15 (peak) and 7.96 +/- 3.2 (mean) after clonidine and pyridostigmine (p less than 0.01); 1499 +/- 887 (AUC), 21.1 +/- 11.8 (peak) and 11.11 +/- 6.6 (mean) after GRF test and 2370 +/- 332 (AUC), 31.4 +/- 3.49 (peak) and 18.22 +/- 3.27 (mean) after GRF and pyridostigmine. The pyridostigmine effect on the simulation by clonidine and GRF is able to potentiate the stimulation of GH and allowed a more accurate diagnosis of GH deficit. PMID- 1758383 TI - [Infantile dermatomyositis. Clinical aspects and prospective treatments]. AB - Juvenile dermatomyositis (DMI) is a rare illness of multisystem inflammatory disease of unknown etiology. It is usually considered as a part of the spectrum of polymyositis/dermatomyositis (PM/DM), and is distinguished from the adult form in having a number of different clinical features as well as distinctive pathologic findings. Although the clinical findings and course of the disease, laboratory evaluation and therapy have been reviewed, many of these studies are old and may not accurately reflect the current status of the disease as it is now defined and treated. Generally it is first diagnosed by the appearance of typical signs in both the skin and muscles. The clinical picture shows early signs of heterogeneity and is confirmed by these latter developments. Its classification falls into three groups: acute single cycle, chronic polycycle and continued chronic; this sickness invariably evolves into one or another of these three. Our current work involves 15 cases of DMI; 8 have acute monocycle, 4 chronic polycycle and 3 continued chronic. This illustrates the clinical and biological heterogenousness of this illness which in itself presents extreme difficulties when considering possible treatment. From our experience, high dose of corticosteroida intraveins have had the best result. Where cases have been acute at the beginning of the sickness and where there has been complications, particularly those of a bronco-pulmonary nature (we treated 3 such cases) it has proven to be beneficial to use corticosteroid together with the immunosuppresant: ciclofosfamide. The use of ciclosporina in one case who had resisted other forms of therapy has appeared to be effective, though this has yet to be verified. PMID- 1758384 TI - [Neuropsychiatric approach to a child with spinal muscular atrophy. A study of relational problems]. AB - Various years' experience of an extensive series of children suffering from progressive chronic spinal muscular atrophy have made it possible to elaborate a neuropsychiatric approach model conducted on the basis of a viewpoint capable of integrating the clinico-medical aspect and aptitude to empathic listening aimed at establishing a therapeutic alliance with the patient. With advancing age and the course of the disease, in most cases very different difficulties and problems are encountered. These change continuously in relation to the stage reached in emotional development. Entry to school and socialisation mark a particular moment in the confrontation with peers and present the ill child with his diversity. With the emergence of adolescent problems, there is also a dramatic new impact between the body image of a wounded, deteriorated self and the evolutionary effort aimed at identifying with the peer group, the autonomisation of parental figures, the integration of a sexed image of the self. Room can be found in this framework for the child neuropsychiatrist who is able to offer himself as a point of reference and set himself up as a model for elaborating disease anxieties. From personal experience it also emerges that in children suffering from a chronic, often fatal disease there is often the need for a physician to coordinate and integrate needs of both a clinical and sociorelational nature for the purpose of allowing the family to get closer to the needs of their child and prevent him from falling prey to destructive type anxieties. PMID- 1758385 TI - [Serum levels of IgG subclasses in critically ill premature infants treated with intravenous immunoglobulins]. AB - Fifty eight premature infants, all needing intensive care and mechanical ventilation, were randomly allocated to two groups. Intravenous immunoglobulins (IVIG, 500 mg/kg Sandoglobulin) were administered to Group 1 while Group 2 received saline as placebo. IgG subclass serum levels were evaluated in both groups on admission, after two hours from the end of IVIG or saline infusion and from day 3 to 7 from birth. IgG subclasses were also measured in 10 healthy term neonates during the first day of life. Results show that after 2 hours from the end of IVIG administration all IgG subclasses reach levels comparable to term neonates. Comparing IgG values between treated and untreated preterm neonates it was observed that on day 3 only IgG1 and IgG3 subclasses were significantly higher in Group 1 than in Group 2. At day 5 no differences were observed between the two groups. IgG2 subclass rose reaching a significant difference between the two groups ad day 5 and 7. Our data show that IVIG single dose (500 mg/kg) administration doesn't produce a constant elevation in all IgG subclasses during the first week of life in the critically ill preterm infant. PMID- 1758386 TI - [Hypothyroidism, transitory or congenital. Reflections on a clinical case]. AB - We report one case of congenital hypothyroidism with thyroid agenesis wrongly considered as a transient form of hypothyroidism. The patient came to our attention at 9 months of age, showing an important delay in neuromotor development. Transient hypothyroidism is a situation of brief hormonal deficit with spontaneous resolution in the first weeks of life. We consider it very important to differentiate this transient condition from a permanent form of thyroid dysgenesis. PMID- 1758387 TI - [Intrahepatic gallbladder. Particulars of a case]. AB - The Authors report a rare case of abnormal position of the gallbladder; the major therapeutical and diagnostic problems are pointed out. PMID- 1758388 TI - [Freeman-Sheldon syndrome. Case contribution and review of the literature]. AB - The paper reports a case of Freeman-Sheldon's syndrome in which a medium-slight degree of mental retardation which was not associated to malformations of the CNS was observed in addition to other typical symptoms. The presence of an hiatal hernia and vesico-ureteral reflow was also noted; to date it is still not possible to establish whether these visceral anomalies are chance findings or whether they are the result of a genetic defect involving tissues of different embryonal origin. Further studies are required to increase our knowledge of Freeman-Sheldon's syndrome and other nosologically related pathologies. PMID- 1758389 TI - [Autoimmune hemolytic anemia in the course of Kawasaki disease. A case presentation]. AB - Kawasaki disease can be characterized by rare complications or by unusual associations. One of these is autoimmune hemolytic anaemia that has been observed seldom up to now. The Authors report a case with this rare association, compare it with cases observed before, and put forth the hypothesis that autoimmune anaemia during Kawasaki disease can be linked to numerous immunological alterations present in mucocutaneous lymph node syndrome. They moreover advise to abstain in these cases from corticosteroid therapy, both to avoid complications, and because, as happened in their patient, this kind of autoimmune hemolytic anaemia can regress spontaneously. PMID- 1758390 TI - [The correlation between blood concentrations of somatomedin C and the auxological characteristics in short-stature subjects]. AB - In this study the authors evaluated the correlation between plasma somatomedin C (SmC) levels and auxological features in 129 short children, who have been subdivided into four groups: classical growth hormone (GH) deficiency (14 prepubertal subjects), normal responses to provocative stimuli tests, but diminished spontaneous GH secretion (40 prepubertal subjects), normal responses to provocative stimuli tests and normal spontaneous GH secretion (45 prepubertal subjects and 30 subjects at stage G2/B2-Ph2 of puberty). The following correlations with SmC are resulted, when all the subjects were considered: chronological age (r = 0.415, p = 0.0002), bone age (r = 0.557, p less than 0.0001), bone age/chronological age ratio (r = 0.493, p less than 0.0001), height SDs (r = 0.574, p less than 0.0001), height velocity SDs (r = 0.599, p less than 0.0001), but not weight variation % (r = -0.020, p: ns). In conclusion, the results of the study demonstrate a high correlation between SmC levels and auxological features, with the exception of weight. PMID- 1758391 TI - [Local immunotherapy prevention of recurrent respiratory infections in children]. AB - A group of 20 children aged between 2.5 and 10 years with recurrent respiratory infections (greater than 6/year) was treated with local immunotherapy (Biomunil spray) for a six-month period (October-March 1988/89). Referring to the same period on last year, a statistically significant decrease of upper respiratory infections was observed (p less than 0.001) as well as an increase of S-IgA rate (p less than 0.001) and less of serum IgA and IgG. The compliance and the tolerance of the drug was good. PMID- 1758392 TI - [A comparison between antigliadin antibodies and blood xylose in celiac disease]. AB - We have compared serum antigliadin antibodies (AGA) with xylose absorption test in diagnosis and follow-up of pediatric celiac disease. Three groups of children were investigated: celiacs, affected by other gastrointestinal disease, healthy controls. On gluten diet AGA IgA, IgG and xylose test were abnormal in all celiac children. After only three months of gluten-free diet, abnormal AGA IgA values were found in 3%, AGA IgG in 63%, xylose test in 28% of children. Normal values for AGA IgA and IgG and for xylose test were found between 7 and 20 months. On challenge, after 1-4 months of gluten diet, abnormal AGA IgA and IgG values were found in 90% of cases, xylose test only in 27%. As far as the children with other gastrointestinal disease are concerned, 2% had abnormal values for AGA IgA, 22% for AGA IgG and 42% for xylose test. All healthy children had normal AGA IgA, IgG values and xylose test. Our date show AGA IgA the most specific laboratory test, among these investigated, for diagnosis and follow-up of celiac disease. PMID- 1758393 TI - [Phakomatosis in childhood. Clinical and instrumental observations of 11 cases]. AB - Taking the institution of the Italian Neuroectodermosis Register (Fois, April 1987) as a starting point, the Authors reviewed their own case-records, including six cases of neurofibromatosis and five cases of tuberous sclerosis, observed during the period 1982/88, and stress the need for early diagnosis (unfortunately often neglected), indispensable both for an effective prevention of any pathological involvement and for precise genetic counselling, susceptible of further improvements thanks to more and more advanced diagnostic techniques. PMID- 1758394 TI - [The efficacy of cyclophosphamide bolus therapy in a girl with SLE with a nephritic onset]. AB - A case of glomerulonephritis as the initial clinical manifestation of SLE in a child is reported. Treatment with oral prednisone did not produce beneficial results either worth respect to the symptoms or the laboratory data. The association with intravenous Cyclophosphamide led to rapid improvement in clinical and serological patterns. Moreover this association has reduced the risk of end-stage renal failure with few serious complications, and no other side effects. PMID- 1758395 TI - [The treatment of nocturnal enuresis. A comparative study between desmopressin and acupuncture used alone or in combination]. AB - During the period from March to September 1989, 40 children suffering from primary nocturnal enuresis, aged between 5 and 14 years, were included in a study to assess the comparative therapeutical efficacy of DDAVP and acupuncture. Children were divided into four groups of 10: group A was treated with DDAVP, group B was treated with acupuncture, group C was treated with DDAVP and acupuncture and group D was treated with placebo (control). The trial design included 3 periods: observation (2 weeks), treatment (8 weeks) and follow-up (4 weeks). Nineteen children completed the study. The efficacy of treatment, which was expressed as a percentage of dry nights, was high in both the DDAVP and acupuncture groups, when used separately. The combined treatment of DDAVP and acupuncture appeared to be the most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results, even after the end of the study. The paper gives a detailed analysis of correlations between type of treatment and urinary osmolarity. PMID- 1758396 TI - [Hydrocarbon poisoning in childhood]. AB - The authors report the experience of a pediatric clinic on hydrocarbon poisoning. Among the reported cases was that of a girl showing a serious pneumonitis. PMID- 1758397 TI - [Endocrine study in the Prader-Willi syndrome. Apropos of 5 cases]. AB - Five children (3 boys and 2 girls) ranging in age form 5-12 years and suffering from Prader-Willi syndrome have been evaluated. In each subject the Authors have examined auxological parameters and the following hormonal values: GH after two pharmacological stimuli tests, gonadotropins after LHRH, TSH and prolactin after TRH, cortisol rhythm, testosterone after hCG in males, thyroid hormones and steroids. The results have shown a height less than 3 degrees centile only in a subjects and ranging from 10 degrees-50 degrees in the others, a weight greater than 97 degrees centile for the height age in all, a low response in GH to both stimuli in two subjects, an increased response to LHRH in FSH in two subjects. All other endocrine evaluations were in the normal range with the exception of insulin that resulted augmented in spite of normal glycaemic values. In conclusion, our data would suggest the existence of an eventual alteration of the hypothalamus-pituitary structures. PMID- 1758398 TI - [Perinatal listeriosis. A report of a case with a hydrocephalus outcome]. AB - Perinatal listeriosis is a disease whose incidence has increased constantly in recent years. Like neonatal infection determined by B hemolyticus streptococcus, the disease appears in two forms: the first is the septicaemic form with early onset, the second form is meningoencephalitic with late onset. We describe a case of listeriosis with immediate onset in which, in spite of the prompt therapy and the normality of rachiocentesis, developed a purulent ventriculitis with outcome in hydrocephalus. PMID- 1758399 TI - [A report of 2 cases of Turner's syndrome with a ring X chromosome]. AB - The authors report two cases of Turner syndrome with clinical evidence of only primitive hypogonadism and short stature. Karyotype analysis showed X ring mosaicism which is present only in 5% of cases of Turner syndrome. The authors agree with the hypothesis suggesting no relationship between break points on the X chromosome and phenotypical aspect. An earlier diagnosis is auspicious so that, using correct therapy, final height should be improved. PMID- 1758400 TI - Long-term effects of toluene inhalation on rat behavior. AB - The effect of inhalation exposure to toluene (3700 mg/m3, 1000 ppm, 21 h/day, 5 days/week, during 4 weeks) on male Sprague-Dawley rats was tested. A wide range of test situations was used, including an operant test with baseline performance and extinction, motor coordination, and exploratory activity. All tests were made 11 to 35 days after the end of the exposure. The results indicate that toluene exposure causes a long-lasting impairment on the extinction process and reduction in the variability of the baseline response in the operant behavior situation. Toluene also had an effect on the water regulation. PMID- 1758401 TI - Behavioral effects of acute exposure to tributyltin chloride in rats. AB - The behavioral effects of a single acute exposure to nonlethal doses of tributyltin chloride (TBTCl) were studied in male Wistar rats. The rats were given TBTCl by oral gavage at doses of 0, 6.3, 12.5, 25.0 or 50.0 mg/kg, and spontaneous motor activity (SMA) and acquisition of conditioned avoidance responses in a shuttle box were monitored. Body weight gain in the 50.0-mg/kg group was significantly lowered, but weight gain in the 6.3-, 12.5- and 25.0 mg/kg groups was comparable to that in the control group. TBTCl caused a dose related decrease in SMA during the dark phase. The 24-h total daily and 12-h nocturnal activity was decreased at doses of 12.5 mg/kg and above. The acquisition of shock avoidance responses was inhibited in all TBTCl-treated groups in a dose-dependent manner, and the difference was significant for rats given TBTCl at doses of 25.0 mg/kg and above. The data indicate that an acute exposure to TBTCl can cause significant changes in rat behavior and suggest that SMA can serve as a sensitive index for detecting its toxicity. PMID- 1758402 TI - Assessment of the acute acrylonitrile-induced neurotoxicity in rats. AB - Acrylonitrile (VCN) is an aliphatic nitrile which is used extensively in manufacturing of synthetic fibers, plastics, and rubber. Although the neurotoxicity of VCN is recognized, no thorough characterization of this effect has been reported. Current studies were designed to quantitatively characterize the acute phase of VCN-induced cholinomimetic neurotoxicity, and to determine the effects of dose, route of administration, and atropine on such toxicity. Administration of a single gavage or subcutaneous doses of 20, 40, or 80 mg VCN/kg to male Sprague-Dawley rats causes two distinctive phases of acute neurotoxic effects. Signs observed in the early phase had a rapid onset, and were cholinomimetic in nature. They included salivation, lacrimation, chromodacryorrhea, polyuria, miosis, vasodilatation in face, ears and extremities, increased gastric secretion, and diarrhea. A late phase developed hours after VCN dosing, and the toxic signs included depression, convulsions, and respiratory failure followed by death at high doses. These results revealed that the cholinomimetic toxicity induced by VCN was dose related regardless of the route of administration. In another study, rats were pretreated with atropine (1 mg/kg, IP) prior to VCN (40 mg/kg) in order to investigate the role of the cholinergic system. Atropine protected rats against VCN-induced cholinomimetic neurotoxicity, suggesting possible involvement of the cholinergic system. Finally, this work provides essential basic information for studying the biochemical, pharmacological, and neurological basis of VCN-induced neurotoxicity in the rat. PMID- 1758404 TI - The postweaning housing environment determines expression of learning deficit associated with neonatal monosodium glutamate (M.S.G.). AB - Perinatal M.S.G. treatment causes a syndrome characterized by damage to the hypothalamic arcuate nucleus, other circumventricular areas, parts of the visual system and the dentate gyrus of the hippocampus. The resulting hormonal dysfunction may be responsible for developmental anomalies of organ systems, obesity, and alterations in sensory/motor performance. We have shown that some behavioral indicators of M.S.G. toxicity in rats can be masked by rearing them in enriched housing conditions. Here, we evaluated the impact of six housing conditions on M.S.G.-induced alterations of organ systems and behavior. Perinatal M.S.G. treatment reduced adrenal, heart and testes weights, as well as total white blood cell (WBC) counts, and increased tail flick latencies. These measures were unaffected by the housing condition. M.S.G.-induced reductions in body weight, grip strength, water maze and dominance task performance varied as a function of housing. Deficits in water maze performance were most evident following social and isolated single-cage housing. We propose that deficits in water maze performance following perinatal M.S.G. may be attributable to hippocampal damage that can be alleviated by rearing the rats in stimulating environments. PMID- 1758403 TI - The effect of prenatal cocaine exposure on umbilical cord length in fetal rats. AB - Umbilical cord length has been considered a reliable indicator of fetal movement. In this study, the effect of prenatal cocaine exposure on umbilical cord length was examined in rats. Pregnant rats were intubated with either 0 or 60 mg/kg cocaine hydrochloride daily from gestation day (GD) 14-21. Fetuses were removed via Caesarean section on GD 21 and umbilical cord length, placental weight and fetal body weight were measured. Fetuses exposed to cocaine in utero had significantly shorter umbilical cords than intubated controls, although there were no differences in placental or fetal body weights. These data suggest that prenatal cocaine exposure suppresses fetal movement, which could contribute to some of the long-term effects observed in cocaine-exposed offspring. PMID- 1758405 TI - Neonatal exposure to triethyltin disrupts olfactory discrimination learning in preweanling rats. AB - Triethyltin is an organotin compound that is known to produce neurotoxicity in both adult and developing organisms. Although this neurotoxicity has been documented with a variety of behavioral and biological measures, the effects of this compound on learning during early development have been less extensively studied. The present study reports four experiments that examined this question with an odor aversion learning paradigm in which pups received presentations of one odor paired with footshock and an alternate odor without shock. In Experiment 1, Long-Evans rat pups were injected IP on postnatal day 5 (PND 5) with either 0, 3 or 5 mg/kg TET and then tested for olfactory discrimination learning on PND 18. Only the 5-mg/kg dose impaired discrimination learning. In Experiment 2, PND 5 exposure to TET (5 mg/kg) disrupted olfactory learning on PND 18 but not on PND 12, whereas exposure on PND 10 disrupted learning at both ages of testing. In Experiment 3, PND 16 exposure to TET (5 mg/kg) also disrupted acquisition of olfactory learning on PND 18 but had no effect on retention of an olfactory discrimination that was acquired prior to TET exposure (i.e., on PND 14 and PND 15). Unconditioned responses to footshock were also unaffected by TET (Experiment 4). These findings indicate that neonatal exposure to TET impairs associative learning in developing rats and are discussed in relation to other studies of the developmental neurotoxicity of this compound. PMID- 1758406 TI - Neonatal exposure to trimethyltin disrupts spatial delayed alternation learning in preweanling rats. AB - Trimethyltin is an organotin compound that produces marked neurotoxicity in both adult and developing animals. The limbic system is a primary CNS target site for this toxicity, and a prominent behavioral effect of TMT is disruption of learning and memory. Impairment of cognitive development has also been suggested by studies showing that rats neonatally exposed to TMT cannot perform spatial working memory tasks during adulthood. However, the question of how early in ontogeny such deficits can be detected has not been addressed. The present study examined this question with a T-maze delayed alternation learning paradigm. Long Evans rat pups, injected IP on Postnatal Day 10 (PND 10) with 6 mg/kg TMT and tested on PND 18, were unable to learn delayed alternation in the manner shown by vehicle control pups. However, TMT- and vehicle-treated groups were both able to learn a simple position discrimination. These findings indicate a selective impairment of spatial working memory by neonatal TMT exposure and show that this impairment can be demonstrated during the preweanling period in the rat. PMID- 1758407 TI - Sexual receptivity of adult female rats prenatally intoxicated with alcohol on gestational day 8. AB - On gestational day 8 (GD 8), pregnant albino rats received two IP injections, spaced by 4 hours, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Adult females exposed to ethanol in utero showed greater sensitivity to estrogen, but not to estrogen plus progesterone, for induction of lordotic response. The 5-HT1 receptor agonist 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) had a significantly smaller effect in inhibiting lordosis response in experimental rats. The greater sensitivity to estrogen and lower sensitivity to the receptor agonist could be a consequence of long-term changes in central neurotransmitter systems induced by acute intoxication with ethanol on GD 8. PMID- 1758408 TI - Maternal recall of alcohol, cocaine, and marijuana use during pregnancy. AB - Alcohol, cocaine, and marijuana use during pregnancy was reported antenatally and at 13 months postpartum by 361 black inner city mothers. The two reports were moderately related for all three substances, but levels reported retrospectively were substantially higher. MAST scores did not differ for the two interviews. Most of the correlations of the antenatal and retrospective reports with maternal and infant characteristics were similar in magnitude; those that differed were somewhat stronger for the antenatal measures. Although the retrospective reports may provide a better indication of mean levels of fetal exposure, they may be less precise in rank ordering among individuals for purposes of correlational analysis. Women with higher MAST scores were particularly prone to report higher levels of both alcohol and cocaine when interviewed retrospectively, and more severely depressed mothers were more likely to report higher levels retrospectively for all three substances. These data suggest that women reporting more than 1.3 drinks/week antenatally (AA/day greater than 0.1) may actually be drinking at levels at risk for alcohol-related birth defects. PMID- 1758409 TI - Elicitation and modification of the acoustic startle reflex in animals prenatally exposed to cocaine. AB - In separate experiments, pregnant Long-Evans rats were administered cocaine orally (60 mg/kg/day) on gestation days 14-21, or subcutaneously (40 mg/kg/day) on gestational days 8-21. For each route of administration, a vehicle control group was pair-fed to the group administered cocaine and another control group was left untreated. Throughout pregnancy, the dams that received cocaine gained approximately 15% less weight than the untreated controls, but none of the dosage procedures affected the size of the litters, or the weight and growth of the offspring. When the offspring reached adulthood, various assessments of reflex function were made using the acoustic startle reflex and prepulse inhibition of startle. There were no effects on startle habituation or reflex modification that could be attributed to the prenatal exposure to cocaine. PMID- 1758410 TI - Failure of acute cocaine administration to differentially affect acoustic startle and activity in rats prenatally exposed to cocaine. AB - Pregnant rats were administered 40 mg/kg of cocaine hydrochloride subcutaneously on gestation days 14 through 21. Rats in one control group were pair-fed to the cocaine group and injected with the saline vehicle during the dosing period, while an untreated control group was simply weighed throughout pregnancy. Maternal weight gain was reduced 13% in the cocaine group and pair-fed controls, but the offspring did not differ in their numbers or growth compared to the untreated controls. The offspring were examined between postnatal days 80 and 96 in tests of the acoustic startle response and open field behavior immediately following acute administration of 0, 5, or 10 mg/kg of cocaine. The acute dosages of cocaine increased the startle response and increased behavior in the open field. There was no evidence that the prenatal treatment altered the baseline in either of these tests. Adult rats exposed prenatally to cocaine entered more quadrants in the open field and reared more frequently than the other groups following the 10 mg/kg dosage of cocaine. However, there was no evidence of an effect of prenatal treatment among the groups administered the 5 mg/kg dosage in the open field test, nor was there a systematic effect of prenatal treatment on the acute effects of cocaine in the acoustic startle test. These data do not provide evidence that prenatal exposure to cocaine can produce persistent changes in the neural systems with which it interacts in the adult. PMID- 1758411 TI - Exploratory behavior and locomotor activity: a failure to find effects in animals prenatally exposed to cocaine. AB - Pregnant Long-Evans rats were administered cocaine orally (60 mg/kg) on gestational days 14-21, or subcutaneously (40 mg/kg) on gestational days 8-21. The oral dosage of cocaine produced some maternal lethality and reduced maternal weight gain throughout the pregnancy by approximately 12%. The subcutaneous dosage regimen reduced the lethality but still caused a decrease in maternal weight gain. Neither dosing regimen affected the number of pups in the litter, their weight, or growth. The offspring of dams that received the oral dosage were examined as adults in an automated holeboard apparatus and were also tested at postnatal day 21 and as adults in an open field. Adult animals exposed prenatally to cocaine did not differ from untreated controls in any of the automated measures of the holeboard apparatus or in the various behaviors, including nosepokes, recorded in the open field. Animals in the vehicle control group did make fewer nosepokes in the open field than the cocaine group, which did not differ from untreated animals. The offspring of dams given the subcutaneous dosage regimen were observed in the open field at day 21. In this case, the prenatal cocaine group had a tendency to make fewer crosses into adjacent quadrants, to rear less often, and to make fewer nosepokes than the control groups. Based on these and other data from our lab, it does not appear that in the rat, prenatal cocaine exposure has pronounced effects on subsequent exploratory behavior and activity in weanling or adult animals. PMID- 1758412 TI - The acquisition of passive avoidance, active avoidance, and spatial navigation tasks by animals prenatally exposed to cocaine. AB - Pregnant Long-Evans rats were administered cocaine orally (60 mg/kg) on gestational days 14-21. One control group was administered the vehicle and another left untreated. Cocaine treatment produced some maternal lethality, and the weight gain of the surviving dams was reduced approximately 15%. Offspring of mothers treated with cocaine did not differ from those of untreated mothers in their numbers, birth weight, or growth. Weanling offspring were tested in a passive avoidance task, and adult offspring were tested for two-way active avoidance and in a spatial navigation task. Although a few animals in the cocaine group showed poor retention of passive avoidance, the group differences were not statistically significant. The adult animals showed normal performance in both the active avoidance and spatial navigation tasks. PMID- 1758413 TI - [Pentamidine against the complications of AIDS]. PMID- 1758414 TI - [Guided regeneration of the periodontal tissues with resorbable and nonresorbale membranes. I. Clinical evaluation]. AB - The present experimental study has been undertaken in order to analyse clinically, in humans, the regeneration of periodontal tissue following two different surgical techniques of guided tissue regeneration therapy using a resorbable and a nonresorbable membrane. Clinical results have demonstrated no statistically significant difference between the techniques employed, both of the showing a favourable outcome if perfect plaque control in the postoperative period is performed. PMID- 1758415 TI - [Guided regeneration of the periodontal tissues with resorbable and nonresorbable membranes. II. Microbiological evaluation]. AB - The present experimental study has been undertaken in order to analyze the influence of bacterial recolonization on periodontal wound healing following guided tissue regeneration therapy in humans. Two different surgical techniques has been carried out: one using a non absorbable membrane and the other a absorbable one. Microbiological data indicate no statistically significant difference between the techniques employed. Furthermore our data have confirmed the necessity of maintaining the healing sites free from the main periodontal pathogens. PMID- 1758416 TI - [An assessment of the proliferative activity in oral lichen planus]. AB - The author's aim was to evaluate the cell proliferation of oral lichen planus, by an in vitro labelling technique using tritiated thymidine (TLI). For this purpose six patients with oral lichen planus and six control volunteers with oral mucosa clinically sound were studied. The cell kinetic parameter was investigated by counting cells from autoradiographs on histological sections of the biopsies. Significant differences were found between the basal TLI of the two group (p = 0.002) but no between the epithelial TLI (Wilcoxon test). PMID- 1758417 TI - [Lesions of the inferior alveolar nerve due to endodontic cements]. AB - The authors report several cases of inferior alveolar nerve injuries caused by endodontic cements. The surgical treatment which is suggested is the decompression of the nerve by microsurgical neurolysis. PMID- 1758418 TI - [Melkersson-Rosenthal syndrome. A case treated with clofazimine]. AB - A 63-year-old woman suffering from scrotal tongue, facial palsy and granulomatous cheilitis (Melkersson-Rosenthal syndrome) is described. Treatment with clofazimine dramatically improved swelling of the lips. PMID- 1758419 TI - [Maxillofacial traumatology in sports practice]. AB - The importance of maxillofacial traumatology in sporting practice is stressed. 1094 patients have been treated for eight years, emphasizing in this way the continuous and constant increase--the incidence of this kind of trauma. PMID- 1758420 TI - [The transmigration of the permanent lower canine]. AB - A rare dental anomaly--the transmigration--is analysed. This condition, which is sparsely recorded in the literature, typically affects the mandibular canine. Twelve cases in which an unerupted mandibular canine has crossed the midline, are described and discussed. Reference is made to considerations put forward in the past by other Authors on this subject, after which personal conclusions are drawn on the diagnosis, etiology and therapy of this rare but serious behaviour of the mandibular canine. The anomaly can be properly diagnosed only by an attentive radiographic evaluation which is primarily based on the orthopantomogram. A series of successive panoramic radiographs taken over years documents the progressive ectopic movement of an unerupted mandibular canine from its developmental site, through the symphysis of the mandible. Lateral, postero anterior cephalometric films and periapical radiographs, provide additional important information. After having analysed the most frequent etiological factors of mandibular canine impaction, the authors present their considerations concerning the probable pathogenetic mechanism of transmigration. In addition to the proinclination of the lower incisors and the increasing axial inclination of the unerupted canine, already pointed out by other authors, an enlargement of the symphyseal cross-sectional area has been observed and documented. In conclusion it is important, also from a therapeutical point of view, to keep under control, by periodical panoramic radiographs, all those clinical situations considered at risk due to their possible evolution in transmigration and which are characterized by: 1) an unerupted canine which can be palpated in a mesial position in the labial sulcus; 2) an enlarged symphyseal cross-sectional area; 3) an obstacle to normal eruption (cysts, odontomas, ecc.); 4) a proinclination of the lower incisors. A progressive worsening of the position of the unerupted canine should induce to consider the possibility of an early interception of this anomalous condition, which, once established, results in the definitive impaction of the tooth. PMID- 1758421 TI - [Osteomas of the jaws. A clinical and rehabilitative problem]. AB - The authors study, based on three cases of maxillary osteoma brought to their attention, evaluates the most suitable type of operation to perform, and the method with which to attention which to approach the problem of postoperative functional rehabilitation. This pathological condition is characterized by slow developments and the late appearance of symptoms deriving from the invasion of surrounding tissues. The chosen technique is surgery, involving the removal of the neoplasm. The benign nature of the neoplasm makes conservative surgery possible, including the partial removal of the neoplasm, in order to preserve the bone tissue indispensable for prosthetic rehabilitation. In cases in which the neoplasm spreads to surrounding tissues, in which more destructive surgery is required with an attendant loss of considerable portions of bone, we have used osteo-muscular pedicle flaps in combination with implantation techniques to obtain adequate functional and prosthetic rehabilitation. PMID- 1758422 TI - [Implant-prosthetic rehabilitation in posttraumatic maxillomandibular tissue losses]. AB - Trauma in the maxillary-facial region can causes loss of mucous, dental and bone tissues, particularly in cases of ballistic trauma in which the explosive force disperses the affected tissues to some distance. This circumstance greatly complicates functional rehabilitation, a process requiring not only the construction of prostheses to replace the lost dental structures, but also the reconstruction of the mucous and bone tissues that will support the prostheses. Using methods involving the formation of pedicle bone grafts and the use of implantation techniques, it has been possible to guarantee a satisfactory functional rehabilitation, and in addition good results from the point of view of appearance have been obtained. PMID- 1758423 TI - [Misoprostol in oral surgery. 112 clinical evaluations]. AB - The efficacy of misoprostol in protecting gastric mucosa during postoperative NSAID therapy was assessed in a sample group of 112 patients of both sexes suffering from gastric pathologies for which they had undergone oral surgery. The analysis of the results confirms the therapeutic efficacy of misoprostol which enabled these patients to conclude the recommended treatment. PMID- 1758424 TI - [Anthropometric assessments in dental esthetics]. AB - Various parameters related to the mobility of the upper lip in a sample of 200 patients, have been considered in order to establish the correlation these have with the extent of lip mobility and the relative visibility of their teeth. From this study it was clear that a large number of patients, with a low index of tooth visibility, could benefit, from the viewpoint of their periodontal health, from the application of prosthetic margins above the gums. This would not damage the aesthetic aspect because the margins in question would only be visible with the lips contracted or, in certain patients, never. PMID- 1758425 TI - Neurologic complications of systemic lymphoma. AB - Lymphoma denotes a heterogeneous group of neoplasms derived from lymphoreticular tissues. It can cause neurologic symptoms by infiltrating into the meninges or brain parenchyma. Alternatively, lymphomas may metastasize to bone or infiltrate into the epidural space via intervertebral foramina to cause neurologic dysfunction by compressing adjacent CNS structures. These direct effects can occur at any time during the disease process; most distressingly, meningeal infiltration may be the initial site of relapse after a complete remission. Diffuse and more undifferentiated lymphomas are much more likely to be responsible for producing either meningeal infiltration or intraparenchymal lesions. Direct CNS invasion by lymphoma is associated with significant patient morbidity and short survival despite intensive therapy; whether this manifestation of lymphoma can be prevented by prophylactic CNS treatment remains uncertain. CNS complications may also occur as a result of indirect effects of lymphoma. Therefore, CNS dysfunction may develop as a result of infections that occur secondary to immunosuppression, as a result of antineoplastic therapies, or as a result of true paraneoplastic syndromes. It is important to distinguish between these indirect effects and tumor progression because their recognition permits frequently available appropriate treatment modalities to be administered. PMID- 1758426 TI - Neurologic complications of systemic cancer. PMID- 1758427 TI - Brain metastases. AB - Brain metastases are the most common intracranial tumors and affect 20% to 30% of patients with systemic cancer. Improvements in diagnostic imaging and recent advances in treatment have resulted in extension of survival and decreased morbidity due to neurologic causes. The overall prognosis, however, remains poor because of the presence of systemic cancer. PMID- 1758428 TI - Metastatic epidural spinal cord compression. AB - It is important to remember that ESCC is a complication of systemic malignancy and usually denotes disseminated disease with poor survival rates. Early diagnosis is crucial. The initial symptom is almost always back pain, which is local, radicular, or both. Following neurologic examination and radiography, MRI scanning or myelography/CT is immediately indicated if radiculopathy or myelopathy is present or if the radiographs of the spine are abnormal. In cancer patients with local back pain and normal findings on neurologic examination and radiography of the spine, there is still a probability of 0.1 of significant ESCC. Therefore, urgent CT/MRI scanning is justified. At present, the best treatment for ESCC remains unknown. In the majority of patients, radiotherapy is the most readily available and appropriate option because it is equal in effect to posterior decompressive laminectomy in both radiosensitive and radioresistant tumors. In patients with posterior epidural disease without tissue diagnosis, laminectomy with or without stabilization should be performed. Posterior decompressive laminectomy alone is contraindicated in patients with vertebral collapse. In selected instances of anterior epidural compression without tissue diagnosis or after failure of radiotherapy, an anterior surgical approach or synchronous vertebral decompression with posterior stabilization may be indicated. In the future, after appropriate clinical trials, vertebral body resection may be the optimal approach in de novo selected patients with ESCC with radioresistant tumors and limited systemic spread of the disease. PMID- 1758429 TI - Central nervous system infections in cancer patients. AB - In the immunocompromised patient, even mild forms of any combination of headache, meningismus, altered mental status, or focal neurologic signs should initiate an evaluation for possible CNS infection. The limited signs and symptoms of acute CNS infection are not due to specific organisms but to pathologic changes at the neuroanatomic site of infection. The initial clinical history, examination, laboratory, and neuroradiographic data will narrow the problem to one of several groups of agents, although it may not be possible to specify a single causative agent. It should be remembered that several concurrent infections (i.e., CMV and toxoplasmosis, aspergillosis, and bacterial sepsis) may be present. Thus, the clinician should rely on broad antibiotic coverage appropriate to the suspected causative agent or agents at the site of infection. It may be necessary to offer broad-spectrum antibiotic coverage for a CSF presentation that is subsequently found to result from a viral illness or from a noninfectious cause. However, one should avoid undertreating those infections for which specific therapy can be offered, and broad-spectrum treatment usually will not be regretted. Uncertainty in diagnosis following noninvasive procedures should lead to a brain biopsy. Although many of the infections discussed in this article have a poor prognosis, some of the most common pathogens, such as Cryptococcus, Listeria, and Toxoplasma, have effective specific therapies to which the patient should have access as rapidly as possible. The clinician who has successfully treated a patient with CNS infection should remain vigilant for late sequelae or recurrence of infection. Chronic treatment of some infections, such as toxoplasmosis or aspergillosis, may be necessary. The reintroduction of steroids for the treatment of an underlying cancer may reactivate previously treated disease, such as cryptococcosis, and periodic CSF surveillance is appropriate under these circumstances. Recurrence of the symptoms should raise the suspicion of recurrent or new infection, and the patient also should be evaluated with CT or MRI for the development of hydrocephalus or for new metastatic disease. In patients who have had varicella-zoster infection, postherpetic neuralgia and delayed arteritis may develop. Seizures, hearing loss, and neuropsychologic sequelae may follow any meningoencephalitis. The patient should always be reevaluated for the possibility of infection with a different opportunistic organism. CNS infections remain a major cause of morbidity and mortality in immunosuppressed patients with malignancies. In one series, 60% of such patients died as a result of their CNS infection, many at a time when the underlying disease had an otherwise good prognosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1758430 TI - Cerebrovascular complications in cancer patients. AB - The clinician should be alert to the possibility of cerebrovascular disease in cancer patients who develop signs of diffuse or focal cerebral dysfunction. The cause of cerebrovascular disease can usually be determined by knowing the primary tumor type, extent of metastatic disease, and type of antineoplastic treatment. Symptomatic infarctions are more common than hemorrhages in patients with carcinoma, and NBTE and cerebral intravascular coagulation are the most common causes of infarction. Brain hemorrhages in patients with carcinoma are usually from hemorrhage into metastatic tumor. Symptomatic hemorrhages are much more common than infarction in patients with leukemia, and hemorrhages may be caused by coagulopathy or central nervous system infiltration. Infarction in leukemia is usually due to septic embolism or intravascular coagulation. By determining the cause of cerebrovascular disease in the cancer patient, the clinician can often recommend appropriate treatment and predict the clinical outcome. PMID- 1758431 TI - Neuromuscular complications of systemic cancer. AB - In patients with cancer, neuromuscular dysfunction often develops as a result of some combination of direct effects of the cancer, from complications of therapy, or from paraneoplastic syndromes. Direct effects include leptomeningeal involvement by tumors (most frequently of the breast and lung) causing polyradiculopathy and compressive brachial and lumbar plexopathies that produce distinctive and typically painful syndromes. The differentiation between radiation and tumor-associated brachial plexopathies may be difficult, however. Peripheral neuropathy is an important dose-limiting toxic side effect of two commonly utilized agents, vincristine and cisplatin. Recent studies have suggested that this complication may be ameliorated or even prevented by prophylactic administration of protective agents. Finally, cancer can cause neuromuscular dysfunction through more remote effects and can produce a variety of paraneoplastic syndromes that include subacute sensory neuropathy. Lambert Eaton myasthenic syndrome, and the neuropathy associated with paraproteinemia. In some syndromes, the presence of specific antibodies that cross-react with both neuromuscular tissues and primary tumors strongly suggests an immune-mediated pathogenesis. In some patients, immunosuppressive therapies and plasmapheresis may relieve symptoms. PMID- 1758432 TI - Paraneoplastic syndromes. AB - The neuromuscular complications of systemic cancer include direct effects (compression or infiltration of peripheral nerve tissues by tumor cells), effects of radiation and chemotherapy, and remote effects. Remote effects constitute the paraneoplastic syndromes--a heterogeneous group of disorders that include motor neuron disease, axon-loss and demyelinating polyneuropathies, Lambert-Eaton myasthenic syndrome, and inflammatory myopathies. PMID- 1758433 TI - Pain syndromes in the cancer patient. AB - Paraneoplastic syndromes affect the nervous system in a very small percentage of patients with cancer. In those patients, portions of the nervous system are damaged or destroyed, usually in association with a small and often occult neoplasm elsewhere in the body. Current evidence suggests that these syndromes occur when the body mounts an immune response to an antigen shared between the tumor and the nervous system. The immune attack is then misdirected against that portion of the nervous system that possesses the "onconeural" antigen. PMID- 1758434 TI - Neurologic complications of chemotherapy. AB - Neurotoxicity is a common and potential dose-limiting complication of cancer chemotherapy. For most agents, high-dose therapy, combination chemotherapy, concomitant cranial radiotherapy, and intracarotid or intrathecal injection are more likely to produce neurologic complications than standard oral or intravenous therapy. Any portion of the nervous system can be damaged. Encephalopathies (either focal or diffuse) are produced by BCNU, cisplatin, cytarabine, 5 fluorouracil, ifosfamide, L-aspariginase, methotrexate, procarbazine, corticosteroids, and some biological response modifiers (interferon, interleukin 2). Cerebellar syndromes may follow the administration of cytarabine, 5 fluorouracil, and procarbazine. Myelopathy may complicate intrathecal methotrexate, cytarabine, thiotepa, and accidental intrathecal vincristine or doxorubicin injection. Peripheral neuropathy occurs from cisplatin, vincristine, and, sometimes, cytarabine or procarbazine. Myopathy is a common complication of corticosteroids. Strokelike syndromes may occur with L-aspariginase, high-dose methotrexate, and intracarotid BCNU or cisplatin. Differentiating the neurologic complications of chemotherapy from other neurologic complications of cancer is often difficult. As cancer patients are treated more aggressively, receive more chemotherapy, and live longer, and as new chemotherapeutic agents are developed and existing agents are used more intensively or in novel ways, neurologic complications of cancer chemotherapy will become more common, serious, and complex. The recognition and treatment of chemotherapy-induced neurotoxicity will become a frequent and important clinical problem for most neurologists. PMID- 1758435 TI - Central nervous system injury by therapeutic irradiation. AB - Therapeutic irradiation is the cornerstone of therapy for many neoplastic diseases but, at the same time, is capable of causing devastating injury to the brain and spinal cord. Thoughtful planning and meticulous execution of radiotherapy reduces the risk of neurotoxicity, but there remains a small and unavoidable risk of serious injury if an effective radiation dose is to be given. It is hoped that better understanding of the mechanisms of radiation injury will lead to safer yet equally effective therapies. PMID- 1758436 TI - Neurologic complications of leukemia. AB - In any patient with leukemia and new neurologic findings, the first entity that must be considered is direct invasion of the nervous system. If that is not a consideration, one must systematically consider cerebrovascular disorders, CNS infections, or metabolic abnormalities as the cause. Finally, one must not overlook radiotoxicity, chemotoxicity, or both in the differential diagnosis. Although some neurologic disorders are stereotyped in their presentation and are relatively easy to recognize, others continue to perplex the physician. Symptoms may be multifactorial in origin, compounding the problem. Leukemia is a systemic disease that may affect the nervous system at any site and at any time during the illness. Now that cure is possible and even to be expected in these diseases, it has become even more important to recognize and alleviate any neurologic morbidity. PMID- 1758437 TI - Molecular mechanics and molecular dynamics studies of the intercalation of dynemicin-A with oligonucleotide models of DNA. AB - Intermolecular molecular modeling calculations to determine the intercalation behavior of dynemicin-A with DNA were performed using both static scanning and energy minimization and molecular dynamics relaxation techniques. Two base pair sequences, CpApCpGpGpGp-3'/GpTpGpCpCp-5' and ApCpTpApCpTp-3'/TpGpApTpGpAp-5', were considered in the calculations. The static scanning and energy minimization analyses identified multiple stable intercalation complexes for each base pair sequence. These complexes were subsequently used as starting structures in molecular dynamics relaxation simulations. Intercalation into the minor groove is preferred for both base pair sequences, and intercalation at a central CG site is preferred by about 9 kcal/mol over a TA site. However, intercalation at a TA site should be more reactive, in terms of chain scission, than that at a CG site, because dynemicin-A has more flexibility to achieve an intercalation geometry disposed to chemically react toward a base adjacent to the 3' side of a purine. This reaction model is consistent with experimental data. PMID- 1758438 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on 17 beta-estradiol-induced glucose metabolism in MCF-7 human breast cancer cells: 13C nuclear magnetic resonance spectroscopy studies. AB - The effects of 17 beta-estradiol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their combination on the metabolism of [1-13C] glucose were determined in cell suspensions of wild-type MCF-7 human breast cancer cells, by 13C NMR spectroscopy. Preliminary studies showed that, during the 7-hr duration of the NMR experiment, the cells maintained their viability and their aryl hydrocarbon responsiveness. Lactate was the major glucose metabolite detected in these studies, and the rate of lactate formation in the untreated (control) and 17 beta estradiol (10(-9) M)-treated cells was 60 and 86 fmol/cell/hr, respectively; this represented a 40% increase in lactate formation in the cells treated with 17 beta estradiol; comparable results were observed for the percentage of glucose converted into lactate. In contrast, TCDD (10(-9) M) did not significantly alter the rate of glucose metabolism or lactate formation. Co-treatment of the cells with 17 beta-estradiol (10(-9) M) plus TCDD (10(-8) to 10(-10) M) showed that TCDD completely inhibited the 17 beta-estradiol-induced metabolism of [13C] glucose to lactate in MCF-7 cells. In contrast, 2,8-dichlorodibenzo-p-dioxin (10( 8) M), a weak aryl hydrocarbon receptor agonist, did not inhibit estrogen-induced glucose-to-lactate metabolism in MCF-7 cells. In addition, it was shown that TCDD caused a significant decrease in 17 beta-estradiol-induced lactate formation within 1 hr after treatment, whereas the induction of monooxygenase activity was not observed until 3 hr after exposure of the cells to TCDD. These data indicate that TCDD-induced 17 beta-estradiol metabolism is not related to the decrease in the rate of conversion of glucose to lactate. These results further define the antiestrogenic responses elicited by TCDD and show that 13C NMR spectroscopy provides a unique method for measuring, in real time, the effects of TCDD on specific metabolic pathways. PMID- 1758439 TI - Expression and pharmacological characterization of a canine 5-hydroxytryptamine1D receptor subtype. AB - RDC4 is a guanine nucleotide-binding protein-coupled receptor clone originally isolated from a canine thyroid cDNA library by Libert and colleagues [Science (Washington D. C.) 244:569-572 (1989)]. We have isolated the corresponding genomic clone for RDC4, have expressed this clone in murine LM (tk-) fibroblasts, and have determined that it encodes a serotonin 5-hydroxytryptamine1D (5-HT1D) receptor. RDC4 is an intronless gene encoding a protein of 377 amino acids, which exhibits greatest sequence identity (43%) to the 5-HT1A receptor and lower overall homology to other serotonergic and catecholaminergic receptors. Membranes prepared from murine LM (tk-) fibroblasts stably transfected with this clone were shown to bind [3H]5-HT in a saturable manner and displayed an apparently homogeneous population of high affinity (Kd = 3.6 nM, Bmax = 275 fmol/mg of protein) [3H]5-HT binding sites. High affinity [3H] 5-HT binding was unchanged using assay conditions [1 microM (+/- )-pindolol and 1 microM (R)-(+/- )-SCH 23390) to pharmacologically mask 5-HT1A, 5-HT1B, and 5-HT1C receptors. Serotonergic ligands displaced specific [3H]5-HT binding with a rank order of potency expected of a 5-HT1D receptor subtype, 5-carboxyamidotryptamine greater than 5-HT greater than yohimbine greater than 8-hydroxy-2-(di-n propylamino)tetralin greater than ketanserin = spiperone greater than zacopride. Further, transfected cells responded to addition of 5-HT by decreasing the level of forskolin-stimulated cAMP accumulation. These data indicate that the gene RDC4 encodes a functional 5-HT1D receptor. PMID- 1758440 TI - Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells. AB - Identification of nonadrenergic binding sites for clonidine and related imidazolines in brain and peripheral tissues and partial purification of an endogenous ligand for these sites have led to the postulation of a novel transmitter/receptor system. The receptors seem to be present in adrenal medulla and to regulate chromaffin cell function. The present study was undertaken to test the ability of the putative endogenous ligand clonidine-displacing substance (CDS) to displace [3H]idazoxan binding to adrenal chromaffin cell membranes and to release catecholamines from cultured chromaffin cells. CDS potently displaces [3H]idazoxan binding to chromaffin cell membranes, with an IC50 of 5 units. The displacement of [3H]idazoxan binding by CDS was not modified by guanosine 5' (beta, gamma-imido)triphosphate, suggesting that the imidazoline binding sites may not be GTP-binding protein-coupled receptors. CDS produced a large release of catecholamines from chromaffin cells, and the release was partially blocked by cobalt, a calcium channel blocker. The calcium-dependent release reached a plateau above 5 units of CDS, with a maximal response at 15 min. It is concluded that endogenous CDS, prepared from brain, regulates the secretion of catecholamines from adrenal chromaffin cells, probably by activating imidazole receptors. PMID- 1758441 TI - Subtype-specific antibodies for muscarinic cholinergic receptors. I. Characterization using transfected cells and avian and mammalian cardiac membranes. AB - Polyclonal antibodies to a number of synthetic peptides corresponding to sequences of human muscarinic acetylcholine receptor (mAChR) subtypes m1, m2, and m4 have been prepared, in order to obtain specific tools with which to study the properties of the different receptors. Hydrophilic peptides from each subtype were chosen from the large intracellular loop between the fifth and the sixth transmembrane domains, because these loops are distinct in each of the mAChR subtypes and contain determinants for coupling to different GTP-binding proteins, as well as potential sites for phosphorylation. Five different antibodies were prepared and tested for their reactivity and specificity toward different mAChR subtypes by immunoprecipitation of ligand-binding activity and receptor protein and by immunoblot analysis. Each of the antisera immunoprecipitated its respective mAChR subtype, as evidenced by precipitation of 50-70% of the ligand binding activity from stably transfected cells expressing the respective mAChR subtype. Very little cross-reactivity toward other subtypes was observed. We used these subtype-specific antibodies to probe the nature of the mAChR subtypes naturally expressed in avian and mammalian cardiac membranes. In tests using the antibodies with cardiac mAChRs, differences in the avian and mammalian mAChR subtypes were detected. Only the anti-m2 antibodies reacted with mAChR from porcine heart, confirming previous pharmacological and molecular biological studies that suggested that this tissue expressed only the m2 mAChR subtype. In contrast, both the anti-m2 and anti-m4 mAChR antibodies immunoprecipitated approximately 50% of the mAChRs solubilized from chick heart membranes. The combined or successive use of anti-m2 and anti-m4 antisera in immunoprecipitation and/or immunoblotting studies with chick heart mAChRs suggested that both antibodies appeared to recognize the same population of mAChRs from that tissue. Taken together, the results show that the subtype-specific antibodies developed in this work are useful in recognizing mAChR subtypes in cells and tissues. These antibodies should be valuable tools for further study of the properties and regulation of mAChR subtypes in various preparations. Evidence that the antibodies can modify mAChR/GTP-binding protein interactions is presented in the accompanying paper. PMID- 1758442 TI - Subtype-specific antibodies for muscarinic cholinergic receptors. II. Studies with reconstituted chick heart receptors and the GTP-binding protein G(o). AB - The antibodies described in the accompanying paper were used to probe the interactions of the chick heart muscarinic acetylcholine receptors (mAChRs) with the GTP-binding protein G(o). The anti-m4b antibodies, which were made against a peptide from the amino-terminal portion of the third cytoplasmic loop of the m4 mAChR subtype, were tested for their abilities to affect the coupling of the chick heart mAChR to the GTP-binding protein G(o). The purified chick heart mAChRs were reconstituted with purified G(o) in phospholipid vesicles, and their interactions were monitored in the presence or absence of the antibodies. The anti-m4b antibodies completely inhibited the ability of G(o) to promote high affinity agonist binding to the purified receptors. The anti-m4b antibodies also completely inhibited the agonist-stimulated binding of guanosine-5'-O-(3 thio)triphosphate (GTP gamma S) to G(o) and the receptor-stimulated GTPase activity of G(o). These findings indicate that the amino-terminal portion of the third cytoplasmic loop is an important determinant for G(o) to promote high affinity agonist binding to the chick heart mAChR and also for the agonist stimulated GTP gamma S binding and GTPase activity. The anti-m4a, anti-m2, and anti-m1a antibodies, which were made against centrally located peptides of the third cytoplasmic loop of the m4, m2, and m1 mAChR subtypes, respectively, were also tested for their effects in the reconstituted receptor/G(o) system. The anti m2 and anti-m4a antibodies also significantly reduced agonist-stimulated GTP gamma S binding, as well as GTPase activity, but did not completely abolish these functions, as was the case with anti-m4b antibodies. However, the anti-m4a and anti-m2 antibodies shared with anti-m4b antibodies the ability to markedly inhibit the ability of G(o) to promote high affinity agonist binding to the purified and reconstituted receptors. In contrast to the results obtained with the anti-m2 and anti-m4 antibodies, the anti-m1a antibodies had smaller effects on the receptor/G(o) interactions. These results suggested that central portions of the loop can also influence mAChR/G(o) interactions. Studies were als performed to test the effects of the peptides that were used as antigens on receptor-mediated GTP gamma S binding to G(o). Each of the peptides caused significant inhibition of this function, but the greatest inhibition was observed with the m4b peptide. In sum, the results suggest that multiple domains in the third cytoplasmic loop of chick heart mAChR can modulate interactions with G(o). PMID- 1758443 TI - Polypeptide toxins from the venoms of Old World and New World scorpions preferentially block different potassium channels. AB - Venoms from five Old World and two New World scorpions were tested for their ability to block various K+ channels in rat brain synaptosomes. A 86Rb efflux kinetic assay was used to identify three types of K+ channels, Ca(2+) independent, voltage-gated, inactivating (A-type) and noninactivating (delayed rectifier) K+ channels and Ca(2+)-activated K+ channels [J. Physiol. (Lond.) 361:419-440, 441-457 (1985)]. The venoms from the Old World scorpions all blocked the A-type K+ channel but not the delayed rectifier K+ channel; only venom from the Israeli scorpion, Leiurus quinqestriatus hebraeus (Lqh), blocked the Ca(2+) activated K+ channel. In contrast, venoms from the two New World scorpions selectively blocked the delayed rectifier K+ channel. Water-soluble components from Lqh venom from the Brazillian scorpion, Tityus serrulatus (Ts), were separated by ion exchange high performance liquid chromatography (HPLC). Seven components that blocked synaptosome K+ channels were isolated from Lqh venom by ion exchange HPLC. All seven components blocked the A-type K+ channel; the five most potent toxins had IC50 values of 18-40 nM. Two of the components from Lqh venom (one identified as charybdotoxin and the other denoted as Lqk4) also blocked a Ca(2+)-activated K+ channel (IC50 = 15 and 60 nM for charybdotoxin and Lqk4, respectively). Five K+ channel-blocking components were isolated from the Ts venom; all five blocked the delayed rectifier channel selectively, and the two most potent components had IC50 values of 8 and 30 nM. Several of the more potent Lqh and Ts toxins were purified to near-homogeneity by reverse phase HPLC. These toxins should be useful as ligands for K+ channel purification, for elucidation of K+ channel structure, and for studies of K+ channel function. PMID- 1758444 TI - Muscarinic receptors in canine colonic circular smooth muscle. I. Coexistence of M2 and M3 subtypes. AB - The parasympathetic neurotransmitter acetylcholine, acting postsynaptically at the smooth muscle muscarinic receptor, is a principle determinant of colonic motility. In order to elucidate the receptor signal-transduction events responsible for muscarinic receptor-induced contraction of colonic circular smooth muscle, we present here and in the accompanying work studies designed to characterize the muscarinic receptors present in colon and to determine their biochemical coupling. Muscarinic receptor subtypes in canine colonic circular smooth muscle were characterized using radioligand binding techniques. The nonselective muscarinic receptor antagonist radioligand [3H]quinuclidinyl benzilate ([3H]QNB) binds rapidly and reversibly to a single class of saturable sites in colon circular smooth muscle membranes, with an affinity (KD) for the antagonist radioligand of 79.8 +/- 12.6 pM and a density of 123.3 +/- 18.7 fmol/mg of protein. Experiments using membranes prepared from isolated cells purified from the circular smooth muscle layer of canine colon (KD = 102.4 +/- 13.5 pM) confirm the smooth muscle origin of the binding and yield a receptor density of 124,340 receptors/cell. The order of potencies of selective muscarinic receptor antagonists in competition with [3H]QNB for binding to colonic receptors is 4-diphenylacetoxy-N-methylpiperidine methobromide greater than methoctramine greater than AF-DX 116 greater than pirenzepine. Unlike other antagonists tested, pirenzepine competition of [3H]QNB binding is biphasic. The high and low affinities deduced from nonlinear fit of the binding data in colon correlate very well with affinities determined for pirenzepine in mixtures of both submandibular gland (M3) and atrium (M2), indicating the presence of two muscarinic receptor subtypes (82% M2, 18% M3) in colon circular smooth muscle. The muscarinic agonist carbachol binds to both high and low affinity sites in colon, and addition of guanine nucleotide (100 microM GTP gamma S) shifts the agonist competition curve to the right, without eliminating high affinity binding sites. Agonist competition studies with a known ratio of M2 and M3 receptors, obtained by mixing pure M2 and M3 populations, predict the result obtained in colon. cDNA probes specific for each of the muscarinic receptors m1 through m4 were hybridized to colon RNA in a Northern blot analysis. Only m2 and m3 probes hybridized to colon RNA, suggesting the presence of both M2 and M3 receptors. Our data demonstrate that the colon circular smooth muscle contains muscarinic receptors of both the M2 and M3 subtypes, which may be coupled to disparate signal transduction pathways important in the physiological actions of acetylcholine in this tissue. PMID- 1758446 TI - Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. AB - Central to the neural mechanism of MPTP-induced parkinsonism is overactivity of the subthalamic nucleus. Lesion of the subthalamic nucleus has therefore been performed in two primates with this condition and found to produce a remarkable amelioration of the disorder. PMID- 1758445 TI - Metal- and photo-induced cleavage of DNA by podophyllotoxin, etoposide, and their related compounds. AB - Podophyllotoxin (PD) and its derivative etoposide (VP-16), a clinically useful anticancer drug, exhibit different mechanisms of action. PD binds specifically to tubulin to prevent its polymerization, whereas VP-16 lacks this action. The DNA strand breakage caused by VP-16 is thought to be due to its interaction with topoisomerase II or to free radical formation by oxidation of its 4'-phenolic hydroxyl group to a semiquinone free radical. We have demonstrated that PD, VP 16, 4'-demethylepipodophyllotoxin (DEPD), and syringic acid (SA) exhibit no DNA cleaving activity but, in the presence of metal ions such as Cu2+ and Fe3+, DEPD and SA form metal complexes, which in turn show high activity for DNA strand scission at pH 7.8 under air. Furthermore, it was found that DNA cleavage was greatly promoted by irradiation with UV light. The PD-Fe3+ system at pH 7.8 showed very low DNA-cleaving activity, but irradiation with UV light in the system induced almost complete DNA breakage. DNA cleavages were significantly inhibited in the presence of hydroxyl radical scavengers, such as sodium benzoate and dimethylurea, in the Cu(2+)-SA and Fe(3+)-PD systems, with or without UV irradiation. These reactions were investigated by optical and ESR spectra, coupled with ESR spin-trapping techniques, by which the formation of hydroxy radicals was clearly detected in all systems. These findings have led us to a new proposal of the metal- and photo-induced mechanism for understanding the antitumor action of PD, VP-16, and their related compounds. PMID- 1758447 TI - Electroconvulsive therapy in Parkinson's disease and other movement disorders. AB - Early case reports note marked improvements in the signs of Parkinson's disease (PD) in several patients with coexisting psychiatric disorders after treatment with electroconvulsive therapy (ECT). Studies since 1959 reveal improvement of parkinsonism in over half of PD patients receiving ECT, regardless of the presence or absence of psychiatric comorbidity. Drug-induced parkinsonism, tardive dystonia, and tardive dyskinesia have also been shown to improve with ECT administration; tic syndromes have achieved mixed results. In animals, ECT enhances dopamine-mediated effects and increases GABA concentrations in the CNS. Optimal parameters relevant to the antiparkinsonism effects of ECT require further study. PMID- 1758448 TI - A case-control study of idiopathic torsion dystonia. AB - A study of 71 patients with idiopathic torsion dystonia (ITD) and 71 matched controls was performed to investigate the range of possible clinical expression of ITD and the role of environmental factors in the development of the disease. A family history of tremor and stuttering were the only factors significantly associated with ITD. No associated environmental factor was identified. PMID- 1758449 TI - Intrafamilial correlation in idiopathic torsion dystonia. AB - Age of onset and severity of idiopathic torsion dystonia (ITD) were studied in 100 British families containing 107 index cases and 79 secondary cases. Analysis of variance of these clinical features did not suggest that ITD is genetically heterogenous, and they were similar in Jewish and non-Jewish patients. Intrafamilial correlation for age of onset was low, particularly between parents and their offspring, suggesting that the ITD phenotype may be determined in part by nongenetic factors or an allelic modifying gene. PMID- 1758450 TI - Inhibition of forearm EMG by palatal myoclonus. AB - The forearm electromyogram (EMG), pharyngeal EMG, and wrist tremor were recorded simultaneously from a 74-year-old woman with the syndrome of palatal myoclonus and progressive ataxia. Her wrist tremor had the characteristics of enhanced physiologic tremor. The enhancement of her tremor was attributable to 50- to 80 ms silent periods in the forearm EMG that followed the 1.9-Hz bursts of palatal myoclonus by 50 to 60 ms. This observation and those of previous authors support the notion that rhythmic olivocerebellar discharges can cause tremorogenic excitation and inhibition of postural EMG activity in the upper extremities. PMID- 1758451 TI - Interobserver reliability between neurologists in training of Parkinson's disease rating scales. A multicenter study. AB - A multicenter study has been conducted to determine the interobserver reproducibility of four of the most frequently used rating scales for Parkinson's disease: the Columbia University Rating Scale (CURS) and the Webster Rating Scale (WRS), both for assessing clinical signs; the Northwestern University Disability Scale (NUDS); and the Hoehn and Yahr staging. Four resident neurologists, inexperienced in the use of the four scales, independently examined 48 parkinsonian patients. The extent to which their assessments agreed was determined by calculating the Cohen k index after the scores had been recodified. The physicians' scores agreed substantially for the CURS and the Hoehn and Yahr scale, while those for the NUDS and the WRS agreed only moderately. Analysis of individual item scores within the scales suggests improvements that would offer greater interobserver consistency. PMID- 1758452 TI - Profile of patients enrolled in a new movement disorder clinic. AB - To assess the need for a regional expertise in movement disorders, the numbers of patients, clinic visits, and medication changes for a new movement disorder clinic were recorded. During 3 1/2 years, 355 patients were seen, with 1,329 clinic visits. Idiopathic Parkinson's disease was the most common diagnosis, comprising 36% of the population, followed by dystonia (17%), tremor (12%), parkinsonism (i.e., Parkinson's plus syndromes, drug-induced parkinsonism, etc.) (10%), chorea (10%), Tourette's syndrome (6.5%), and tardive dyskinesia (3.4%). Distribution of follow-up visits was similar, with Parkinson's disease (52%) being most frequent and Tourette's syndrome (3.1%) least frequent. The relative utilization of medical care by each patient group was assessed by determining the number of medication changes and the number of clinic visits per follow-up year. No differences in these measures were found using a one-way analysis of variance. Of the Parkinson's disease patients, 67% had Hoehn and Yahr stages III-IV and 77% of the clinic visits were made by this subgroup. When considered in light of the prevalence of each of the diseases, these data show a need for an expertise in movement disorders for a population base of the size we have served. PMID- 1758453 TI - Idiopathic Parkinson's disease combined with multiple system atrophy. A clinicopathological report. AB - The clinical and postmortem findings of a patient with Lewy body pathology combined with multiple-system atrophy are described. When alive the patient was diagnosed as having Parkinson's disease. Pathological examination found evidence of striatonigral and olivopontocerebellar degeneration, together with Lewy bodies at a number of sites characteristic for idiopathic Parkinson's disease. Taken together, the clinical history and histological findings support the coexistence of two disease processes. PMID- 1758454 TI - Steroid-responsive chorea in moyamoya disease. AB - We report the case of a 13-year-old boy with disabling chorea due to moyamoya disease. His chorea seemed to improve with steroid therapy. We conclude that steroid therapy may ameliorate moyamoya-associated chorea, and perioperative steroids can confound neurosurgical outcome. We are unable to assess the effect of cerebrovascular bypass procedures on the outcome of chorea in this patient. PMID- 1758455 TI - Segmental ballistic movement overflow myoclonus: a clinical, electromyographic, and pharmacologic evaluation. AB - A 27-year-old man presented with a sporadic, nonprogressive, right-sided, segmental movement disorder that had started at the age of 2 years. Ballistic movement overflow myoclonus was diagnosed clinically and by surface electromyography. Special investigations did not detect anything except atrophy of the left temporal lobe on CT scan. The movement intensity was attenuated by alcohol but was minimally affected by high doses of oral propranolol (320 mg daily), clonazepam (36 mg daily), or trihexyphenidyl (32 mg daily). High-dose intravenous biperidine (10 mg) resulted in dramatic improvement, but with unacceptable side effects. The possible role of a cholinergic disturbance in generating myoclonus is discussed. PMID- 1758456 TI - Extending the concept of ballistic movement overflow myoclonus. PMID- 1758457 TI - Complex stereotypies after right putaminal infarction: a case report. AB - A 17-year-old boy is described who experienced circling behavior interrupting his gait and complex stereotyped movements of the hands after a complicated repair of an aortic coarctation. An MRI scan showed a right putaminal infarct. The boy's behavior and stereotypies bear a close resemblance to those found in autism. PMID- 1758458 TI - What is it? Case 1, 1991: a severe and fatal systemic illness first presenting with a movement disorder. PMID- 1758459 TI - What is it? Case 2, 1991: unusual tremor, myoclonus, and a limping gait. PMID- 1758460 TI - What is it? Case 3, 1991: moaning in a man with parkinsonian signs. PMID- 1758461 TI - Blepharospasm associated with pseudohypoparathyroidism and bilateral basal ganglia calcifications. PMID- 1758462 TI - Thalamic demyelination and paroxysmal dystonia in multiple sclerosis. PMID- 1758463 TI - Neuroleptic malignant-like syndrome associated with acute hydrocephalus. PMID- 1758464 TI - Levodopa-associated hemifacial dystonia. PMID- 1758465 TI - Tourette's syndrome in twins. PMID- 1758466 TI - IL-2 gene transfer in immunotherapy of cancer: local administration of IL-2 activated lymphocytes and X63-m-IL-2 cells constitutively producing IL-2 inhibits growth of plasmacytomas in syngeneic mice. AB - Peritumoral administration of X63-m-IL-2 cells, transformed by IL-2 cDNA and constitutively producing large quantities of IL-2, was effective in mediating regression of X63-Ag8.653 plasmacytomas transplanted in syngeneic mice. Injection of killer cells with LAK activity substantially enhanced the tumor-inhibitory effect of IL-2-producing cells. In vitro activation of murine bone marrow and spleen cells with IL-2 produced by the X63-m-IL-2 cell line resulted in generation of lymphocytes with oncolytic activity against X63-Ag8.653 plasmacytomas and a variety of other target cell lines. The cytolytic activity of adherent IL-2-activated killer cells (A-LAK) was substantially higher than that of a nonadherent subset. Bone marrow and spleen cells from both healthy control and tumor-bearing mice contained LAK precursors, but the cytolytic activity derived from tumor-bearing mice was lower than that from healthy controls. PMID- 1758467 TI - Growth and dissemination of human malignant lymphoblasts in immunosuppressed nu/nu mice. AB - Athymic nu/nu mice are commonly employed for the heterotransplantation of solid human tumors. Leukemias, however, have consistently proved difficult to transplant and, to enhance their take, recipient nu/nu mice have been variously immunosuppressed. In this study, the natural reactivity against human malignant T lymphoblast (PF382) of splenectomized nu/nu mice (S-nu/nu), nu/nu mice splenectomized and treated with polyinosinic-polycytidylic acid (SIC-nu/nu), and nu/nu mice splenectomized, irradiated and repeatedly injected with antiasialo GM1 antiserum (SIA-nu/nu) has been correlated with the in vivo growth of subcutaneous and intravenous PF382 cell challenges. SIC-nu/nu mice display a marked natural killer (NK) activity, quickly clear 125I-Urd-labelled PF382 cells injected intravenously and do not allow the growth of subcutaneous nor intravenous PF382 cell challenges. S-nu/nu mice display a slightly lower NK activity and slower clearance of 125I-Urd-labelled PF382 cells. Moreover, an intravenous PF382 cell challenge kills 56% of S-nu/nu mice. SIA-nu/nu mice have no NK activity, slowly clear 125I-Urd-labelled PF382 cells and always allow the growth of PF382 cells injected either subcutaneously or intravenously with a consistent pattern. Following the intravenous challenge, PF382 cells first metastasize to liver and kideny, then focal or diffuse infiltrations of the bone marrow and menings become evident. SIA-nu/nu mice thus offer an interesting experimental model for study of the pathogenesis of leukemic infiltration of the meninges, and the exploration of possible therapeutic approaches. PMID- 1758468 TI - Quantitation of natural killer cell function and risk of metastatic poorly differentiated head and neck cancer. AB - Previous laboratory studies have suggested that natural immunity is a primordial defense mechanism against blood-borne metastatic cancer, its function being most effective against dedifferentiated, low-major-histocompatibility-complex-class-I antigen-expressing tumors. In this clinical study, 263 previously untreated patients with squamous cell carcinoma of the upper aerodigestive tract were evaluated for natural killer (NK) cell cytotoxicity mediated by peripheral blood lymphocytes against K562 target cells. All patients were evaluated before treatment, underwent subsequent attempts at curative therapy in which they were initially rendered disease-free, and then followed longitudinally for clinical outcome. Using a Cox proportional hazards model, quantitated NK cell cytotoxicity was inversely related to subsequent death with disease (p = 0.05), regional metastases (p = 0.008) and distant metastases (p = 0.03). No relationship between NK cell function and local recurrence could be identified (p = 0.81). Patients were further stratified by degree of differentiation of their respective primary cancer. The prognostic implication provided as to risk of death with disease and progressive metastatic growth was confined to the population with moderate-to poorly differentiated cancers. Conversely, its function was nonpredictive in patients with well-differentiated cancers; the latter cancers were observed to express higher levels of major histocompatibility complex-class I framework antigens. Results of this clinical study are consistent with previous laboratory investigations and suggest that, within humans, the NK cell functions in metastatic sites against more primitive cancers. Such findings may have implications in designing therapeutic strategies. PMID- 1758469 TI - [Design of a species-specific DNA probe based on the pFra plasmid of the plague pathogen]. AB - The recombinant plasmid pBS1 carrying a 2 kb SalGI fragment of Yersinia pestis pFra plasmid was constructed by insertion of the fragment into a vector plasmid pBR327. SalGI-BspRI 400 bp subfragment was recloned into a pBR322 vector plasmid. Open reading frame was found in the fragment by DNA sequencing technique. The subfragment designated F1-probe permits one to identify specifically the Yersinia pestis strains harbouring pFra plasmid, thus, differing them from closely related Yersiniea and other representatives of Enterobacteriaceae family. PMID- 1758470 TI - [Mutagenesis, induced by phosphotriester analogs of oligonucleotides and directed to the cleavage site of double-spiral DNA]. AB - The mutagenic properties of phosphotriester analogues revealed in course of interaction with linearized plasmid DNA were studied. The plasmid-based model system permitting one to test reliably the induced mutations is proposed. The efficiency of mutagenesis was shown to depend on the length of the oligonucleotide-mutagen and the genotype of the transformed Escherichia coli strain. The possible mechanisms involved in mutagenesis are discussed. PMID- 1758471 TI - [Assessment of the genotoxicity of the "Binase" enzyme preparation]. AB - "Binase" enzyme sample (a microbial ribonuclease) has been tested for mutagenicity in a set of tests. The set included Ames test Salmonella/microsome, Escherichia coli Rec-test, bacteriophage induction assay, DNA-repair synthesis in lymphoid cells. "Binase" is shown to possess a small genotoxic effect at high concentrations. Both animal and plant S-9 fractions eliminated the effect. PMID- 1758472 TI - [Transfer of transformation and conjugation plasmids from Escherichia coli to Bacillus subtilis and Azospirillum brasilense]. AB - The conjugative transfer of RP4 plasmid from Escherichia coli to Azospirillum brasilense was detected after introduction and subsequent incubation of these microorganisms in soil. The plasmid transfer via transformation from Escherichia coli to Bacillus subtilis was observed in case both bacteria were growing together in sand containing sucrose solution. The possible reason for low frequency interspecies plasmid transformation under conditions close to natural habitats is poor survival of "domesticated" rather than wild type Bacillus subtilis strains and lack of competence state in this case. PMID- 1758473 TI - [Study of Brevibacterium flavum phage PhiBSh6]. AB - Properties of a virulent Brevibacterium flavum bacteriophage phi BSh6 were studied. The phage was placed in morphological group B1 according to Ackerman classification, head diameter being 74-3 nm, tail length being 337 +/- 15 nm. The phage was shown to have double stranded DNA as a genetic material. The chromosome is linear having cohesive ends. Chromosome length was estimated to be about 71 kbp by restriction analysis and electron microscopy. A unique EcoRI-EcoRI fragment of bacteriophage DNA (0.8 kbp) was cloned in Escherichia coli. Restriction chart of cos region was determined, the dyad symmetry being absent from cos sequence. Deletion mutant of the phage was obtained and restriction map of the corresponding genome region was constructed. The phage phi BSh6 was shown to be a close relative to phages phi B and BB14 described earlier. PMID- 1758474 TI - Determination of Cd, Co, Cu, Fe, Pb, Mn, Ni and Zn in diets: development of a method. AB - A method useful for the determination of cadmium, cobalt, copper, iron, lead, manganese, nickel and zinc in diets is described. Organic matter is destroyed applying a wet procedure, and element content is measured by flame atomic absorption spectroscopy (FAAS) in the case of copper, iron, manganese, nickel and zinc, and by graphite furnace (GF-AAS) in the case of cadmium, cobalt and lead. The matrix interference study is carried out. Values found for linearity, detection and quantitation limits as well as accuracy show that the described method is useful to determine the elements taken into account at usual levels in diets. PMID- 1758475 TI - Determination of carotenoids in foods by high-performance liquid chromatography. AB - The mean values of alpha and beta-carotene of 10 fruits and vegetables from supermarkets in Cairo and Alexandria have been determined using HPLC method, and the average vitamin A activities (in retinol equivalents) calculated. Carrots, spinach and sweet potatoes were the best sources of provitamin A activity. Beta carotene was the more prevalent carotenoid compared with alpha-carotene. An analysis of variance including all foods investigated demonstrated that there were no significant differences among either locations or times of analysis. There was no difference between the analysed values of vitamin A activity and the USDA Handbook No. 8 values. PMID- 1758476 TI - [The preparation of food and environmental samples for residue analysis of pesticides and PCBs by continuous steam distillation]. AB - The treatment of water, soil and food samples was tested with a modified equipment of glass for simultaneous steam distillation/solvent extraction. Spiked samples with 22 pesticides (most of them contained halogen) and PCB yielded good or very good recoveries after 1.5 h for water samples and after 5 h for soil and plant food samples, respectively. This method is ecologically beneficial, and because it needs only a small amount of solvent (less than 10 ml) it is not expensive and may be used as a quick screening in several fields. PMID- 1758477 TI - [The determination of protein content of milk, cheese, and meat with the use of the biuret reaction]. AB - A review is given of the different composition of biuret test solutions and experiments with the estimation of protein content of milk, cheese and meat by means of the biuret method are reported. The pure protein and the casein content of skimmed milk and the protein content of whole milk could be determined with biuret test solutions containing potassium hydroxide and a detergent. The use of the biuret method is advantageous in the case of cheese and meat, which are dissolved in potash lye or alkaline detergent solutions. Disturbances of the biuret method caused by lactose, fat or turbidity were eliminated after addition of hydrogen peroxide, by means of extraction or of additional measurements with a copper-free, zinc-containing biuret reagent. Deviations of the color intensity of biuret complexes were compensated by inclusion of standards in the measurement series. PMID- 1758479 TI - [Obstructive cholangiopathy and isothiocyanate]. PMID- 1758478 TI - [Determination of aflatoxin M1 level in milk in the production of baby and children's food using immunoassay]. AB - Using commercial immunokits the concentration of aflatoxin M1 was measured in 376 samples of raw milk from farms in the area of a new dairy plant producing milk baby foods. 87.8% of the samples contained no aflatoxin M1 (detection limit 0.025 micrograms/l) and only 2 samples (0.5%) possessed higher concentration than 0.1 microgram/l, which represents the tolerance limit for aflatoxin M1 in baby milk foods admitted in Czechoslovakia. PMID- 1758480 TI - Neurotoxicity of methamphetamine: mechanisms of action and issues related to aging. PMID- 1758481 TI - The environmental impact and adverse health effects of the clandestine manufacture of methamphetamine. PMID- 1758482 TI - Heavy metal and organic contaminants associated with illicit methamphetamine production. PMID- 1758483 TI - Pyrolytic characteristics, pharmacokinetics, and bioavailability of smoked heroin, cocaine, phencyclidine, and methamphetamine. PMID- 1758484 TI - Methamphetamine abuse in California. PMID- 1758485 TI - Trends and patterns of methamphetamine smoking in Hawaii. PMID- 1758486 TI - Methamphetamine abuse in Japan. PMID- 1758487 TI - Trends and patterns of methamphetamine abuse in the Republic of Korea. PMID- 1758488 TI - The Party's dead, but the party goes on. PMID- 1758489 TI - DNA fingerprinting discord. PMID- 1758490 TI - Electronic arts imitate life. PMID- 1758491 TI - Rabies. Immunization in the field. PMID- 1758492 TI - Oligonucleotide drugs. A change of backbone. PMID- 1758493 TI - Formation and resolution of recombination intermediates by E. coli RecA and RuvC proteins. AB - The recombination of DNA molecules has been reconstituted in vitro using two purified enzymes from Escherichia coli. RecA protein catalyses homologous pairing and strand exchange reactions to form intermediate DNA structures that are acted upon by RuvC. The newly identified RuvC protein resolves the intermediates by specific endonucleolytic cleavage to produce recombinant DNA molecules. PMID- 1758494 TI - Large-scale eradication of rabies using recombinant vaccinia-rabies vaccine. AB - Rabies infection of domestic and wild animals is a serious problem throughout the world. The major disease vector in Europe is the red fox (Vulpes vulpes) and rabies control has focused on vaccinating and/or culling foxes. Culling has not been effective, and the distribution of five vaccine baits is the only appropriate method for the vaccination of wild foxes. Although some European countries have conducted field vaccination campaigns using attenuated rabies virus strains, their use has not been extensively approved because they retain pathogenicity for rodents and can revert to virulence. These strains cannot be used in North America because they are pathogenic for the striped skunk (Mephitis mephitis) and are ineffective in the raccoon (Procyon lotor). We have constructed a recombinant vaccinia virus, VVTGgRAB, expressing the surface glycoprotein (G) of rabies virus (ERA strain). The recombinant was a highly effective vaccine in experimental animals, in captive foxes and in raccoons. We report here the results of a large-scale campaign of fox vaccination in a 2,200 km2 region of southern Belgium, an area in which rabies is prevalent. After distribution, 81% of foxes inspected were positive for tetracycline, a biomarker included in the vaccine bait and, other than one rabid fox detected close to the periphery of the treated area, no case of rabies, either in foxes or in domestic livestock, has been reported in the area. PMID- 1758495 TI - Restoration of antigen presentation to the mutant cell line RMA-S by an MHC linked transporter. AB - In mammalian cells, short peptides derived from intracellular proteins are displayed on the cell membrane associated with class I molecules of the major histocompatibility complex (MHC). The surface presentation of class I-peptide complexes presumably alerts the immune system to intracellular viral protein synthesis. Peptides derived from the cytosol must reach the cisternae of the endoplasmic reticulum where they are required for the assembly of stable class I molecules, and it has been proposed that the products of the two MHC-encoded ATP binding cassette (ABC) transporter genes function to deliver the peptides across the membrane of the endoplasmic reticulum. This idea is supported by experiments in which transfection of a human cell line defective in class I expression with a complementary DNA of one of these genes restored cell surface expression levels. Here we show that the complete phenotype of the mouse mutant cell line RMA-S, in which lack of surface expression of stable class I molecules correlates with an inability to present viral peptides originating in the cytosol, is repaired by the cDNA of the other transporter gene. These results are consistent with the possibility that the two transporter polypeptides form a heterodimer. PMID- 1758496 TI - [Algorithms, brains, computers. What they know and what they do not. I]. AB - Our concern for machines and for their abilities, though quite ancient, has increased with the outstanding achievements of modern computers. What, then, is typical of a machine? Is its output really limited by our input? For questions like these, an appropriate tool is the concept of algorithm. Algorithms are best characterized as mental tools ("Denkzeuge"). PMID- 1758497 TI - Unusually high levels of thyroid hormones in isolated and/or monolayer-cultured pig thyroid epithelial cells. PMID- 1758498 TI - [Of what benefit is a research internship in the tropics for Dutch medical students?]. PMID- 1758499 TI - [DNA duplication in hereditary type Ia motor and sensory neuropathy (Charcot Marie-Tooth disease)]. PMID- 1758500 TI - [There is no such thing as the CVA]. PMID- 1758501 TI - [Injuries due to fireworks at the turn of the year 1990/'91]. AB - During the festivities at the turn of the year 1990, 58 patients with firework related injuries were seen. A 200% increase in relation to previous years was observed. Minor blast injuries of the hand were the most frequent. Many children of Turkish and Moroccan nationality were involved. It was surmised that illegal and unsafe fireworks in combination with careless behaviour were causative factors. Prevention should be achieved through amending the law on use and distribution of fireworks and through intensifying and fine-tuning the annual information campaigns. PMID- 1758502 TI - [Accidents a matter of chance? The significance of lunar phases and biorhythms in trauma patients]. AB - The belief that supernatural forces influence man's fate appears to be increasing. Many people are convinced that unknown forces can cause injuries. From a multitude of proposed possibilities, we selected two factors that are claimed to affect the incidence of accidents. The first theory holds that more accidents occur at the time of full moon. The second theory concerns the three so called biorhythms with their supposedly critical days (physical, emotional, intellectual). The effect of the lunar phase and the three biorhythms on accidents was determined from the dates of accident and birth of trauma patients admitted to the University Hospital in Groningen. We analysed data on all 29085 patients who were seen at the outpatient department in the years 1981-1983 and on 930 severely injury patients admitted in the years 1985-1989. At full moon even slightly fewer patients than expected (24 percent vs 25 percent) were seen at the emergency department. The number of severely injured patients was the same during the four moon phases. The 'critical' biorhythm days were not associated with increased number of accidents, neither for the patients seen at the emergency department, nor for the severely injured patients. PMID- 1758503 TI - [150 years of life expectancy of Dutch members of parliament; 1848-1989]. AB - To determinate whether the stressful lifestyle of members of parliament (MP) might lead to excess mortality, as suggested in British Medical Journal in 1989, we investigated the mortality and life expectancy of 1589 members of the Dutch parliament over the period 1848-1989. Total mortality (all causes) for members of parliament who had been in function for at least one year (n = 1472) was compared to that of the general population of the Netherlands, adjusted for age, sex and calendar period. We calculated a standardized mortality ratio (SMR) from beginning of exposure as well as from ten years after entry in order to correct for a healthy cohort effect. The total number of deaths was 986 (863 with follow up after 10 years after entry) and did not exceed the expected number of deaths based on population mortality rates. We conclude that MPs have no higher death risk than those who elected them, although one might have expected a lower death risk because of their social background. PMID- 1758504 TI - [A tuberculosis project in Ecuador]. AB - OBJECTIVE: Determination of the frequency of pulmonary tuberculosis in an Indian community in Ecuador among symptomatic patients and contacts of patients with tuberculosis. Pulmonary tuberculosis was defined as the presence of acid fast rods in sputum. SETTING: Pontificia Universidad Catolica del Ecuador, Quito, Ecuador. DESIGN: Sputum samples were collected with the aid of an educational drama. About 5000 persons were informed on tuberculosis by this performance. The sputum samples from 241 persons were examined for presence of acid-fast rods with a direct Ziehl-Neelsen (ZN) stain and a ZN stain after concentration of the sputum. If ZN stain was negative, the sputum was cultured on Lowenstein-Jensen medium or on Coletsos medium. The Lowenstein-Jensen medium was past the expiration date. RESULTS: Bacteriological examination of the sputum samples from 241 patients and controls brought to light 65 (26.9%) individuals with acid-fast rods in the sputum. Forty per cent of the affected patients were between the ages of 20 and 34. Investigation of 82 contact persons revealed 19 (23.2%) positive cases. The results of culturing of the sputum samples were disappointing: only 6 of 152 (3.9%) samples showed growth of acid-fast rods. CONCLUSIONS: The frequency of pulmonary tuberculosis (as defined by the presence of acid fast rods in sputum) is high in the community investigated, much higher than the official data on the prevalence of tuberculosis indicate. It is important to investigate contacts of patients with pulmonary tuberculosis to trace a source and to trace new cases. PMID- 1758505 TI - [Dutchmen and the development of the microscope]. PMID- 1758506 TI - [A monograph by K.F.H. Marx from 1838; possibly the first clinicopathological description of multiple sclerosis]. PMID- 1758507 TI - [The short extensor muscle of the hand, an 'old' muscle, as the cause of pain in the hand]. PMID- 1758508 TI - [Desmopressin and nocturnal enuresis]. PMID- 1758509 TI - [Diabetic retinopathy: agreement of funduscopic assessment by the family physician and the ophthalmologist]. PMID- 1758510 TI - [Gynecomastia; the patient's fate is in your hand]. PMID- 1758511 TI - [Halcion: requiem for a kingfisher?]. PMID- 1758512 TI - [Cell biology from a medical perspective. IX. Cell-cell and cell-matrix interactions]. PMID- 1758513 TI - [Myelodysplastic syndrome]. PMID- 1758514 TI - [Surgical treatment of hip fractures in 90-year-olds]. AB - During 1973-1987 178 patients of 90 years and over were operated for a fracture of the hip in the Diaconesseninrichting 'Bronovo', The Hague. Fifty patients were suffering of senile dementia which made reactivation difficult and contributed to 43% of the mortality. The overall in-hospital mortality was 18% and the survivors were discharged after 35 days on average. Patients with lateral and pertrochanteric fractures were treated according to McLaughlin (6), to Ender (74) and with a dynamic hip screw (17) and medial fractures with a dynamic hip screw (54) or a prosthesis (27). The in-hospital mortality rates were 16, 28, 6, 11 en 11% respectively. Postoperatively 7 Ender pins sagged out and 6 patients treated with a dynamic hip screw secondarily needed a prosthesis, 3 of them after discharge. It is advised to use Ender pins in lateral or pertrochanteric fractures in inactive patients only, and a dynamic hip screw in active patients; in medial fractures a dynamic hip screw only in inactive patients and in others a prosthesis. An increase in the number of very old people with hip fractures is to be expected in the near future. PMID- 1758515 TI - [Epidemiological surveillance of antibiotic resistance in a general hospital for the assessment of 'blind' antibiotics policy]. AB - A study was made of the epidemiology of gentamicin-resistant Gram-negative rods in a large general hospital over the last 12 years, and of the consequences of the presence of these bacteria for antibiotics policies, especially the use of gentamicin. Resistant bacteria were endemic at a low level: of the clinical isolates, 670 from 488 patients contained resistant bacteria, 2% of all Gram negative rod isolates. Sporadically there were minor epidemics. Especially seriously ill, elderly patients became infected. Every year multiresistant bacteria contributed to a number of deaths. The choice of gentamicin as a drug of first, blind, choice in life-threatening infections remained justified. Continuous monitoring of Gram-negative rods is an important instrument for a preventive policy. PMID- 1758516 TI - [Mycobacterium avium disease in AIDS patients; diagnosis and therapy]. AB - In eight (25%) of 32 consecutive AIDS patients between 1986 and 1989, Mycobacterium avium infection was diagnosed: in seven disseminated, in one as a local lymph node process. Six patients were treated as consistently as possible with a combination of ethambutol, rifabutine, clofazimine and protionamide (or cycloserine) in relatively large dosages. Median survival of treated patients was 15.5 (4-22) months. Protionamide inhibited most M. avium strains (7 of 8) in vitro, but often caused intolerance (nausea). Treatment of disseminated cytomegalovirus infection in our opinion was necessary in 5 of 6 patients during longterm M. avium therapy. HIV therapy (Zidovudine) during M. avium treatment was not possible due to bone marrow depression. A low maintenance dose of corticosteroids was necessary in 3 of 6 patients (one with adrenal insufficiency) to suppress symptoms such as fever and malaise. PMID- 1758517 TI - [Chronic conjunctivitis caused by oral anaerobic germs]. AB - A patient with chronic, unilateral conjunctivitis is presented. The predominant bacterial flora consisted mainly of Prevotella intermedia (formerly Bacteroides intermedius) and Peptostreptococcus micros. Restriction endonuclease fingerprinting of genomic DNA demonstrated that P. intermedia most probably originated from the oral cavity. In the oral cavity this species was recovered from the dorsum of the tongue, the tonsillar area and the periodontal pockets. Topical treatment with various antibiotics had failed to cure the infection in the past. The condition was cured after systemic therapy with metronidazole and amoxicillin. PMID- 1758518 TI - [Angiotensin converting enzyme inhibitors in the treatment of proteinuria]. PMID- 1758519 TI - [Blisters in pregnancy: herpes gestationis]. PMID- 1758520 TI - [Reduction of the thyroid gland by radioactive iodine in patients with a large struma]. PMID- 1758521 TI - Survival and adequacy in long-term hemodialysis. PMID- 1758522 TI - Accuracy of hemodialysis urea kinetic modeling. Comparison of different models. AB - To test the accuracy of urea kinetic modeling (UKM), the classic fixed-volume model UKMf, two variable-volume models (UKMvb and UKMvd), direct dialysis quantification (DDQ) and a partial dialysate collection method (PDC) were evaluated in 15 stable, high-hematocrit patients. Urea generation rate (G) was also determined from a 1-week collection of total dialysate and urine (OWC). The results, except distribution volumes, were highly correlated. However, Kt/V, the normalized whole-body urea clearance, was about 8% higher with UKMvb and UKMvd. Two of three simple equations for Kt/V rendered grossly deviating, but highly correlating, results. The normalized protein catabolic rate was 8% higher with UKMvd. With OWC as reference, UKMvb and UKMvd overestimated G by 19 and 15%, respectively. All results of PDC closely followed those of DDQ. This method may be an alternative for exact quantification. Before using a new UKM method it should be compared to an established reference method. PMID- 1758523 TI - Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion. AB - The tubular transport of urate was studied in 40 hypertensive patients and in 20 normal subjects by means of pyrazinamide and benzbromarone tests. There was a marked decrease in urate excretion per nephron in hyperuricemic patients with essential hypertension. Serum uric acid correlated inversely with fractional excretion of urate (r = -0.7450, p less than 0.001). Presecretory and postsecretory reabsorption of urate did not significantly differ between hypertensive patients with high uric acid levels and control subjects. Urate secretion was significantly reduced in hypertensive patients and in those with hyperuricemia showed a twofold decrease. Serum uric acid correlated inversely with tubular secretion of urate (r = -0.7091, p less than 0.001) in hypertensive patients. These findings indicate that impaired tubular secretion of urate is a potential mechanism of hyperuricemia in essential hypertension. PMID- 1758524 TI - Acute effects of ciclosporin on renal hemodynamics and urinary protein excretion in patients with the nephrotic syndrome. AB - The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758525 TI - Urinary detected renal antigens in the early diagnosis of kidney graft rejection. AB - The determination of renal antigens in the urine with an immunoassay, based on monoclonal antibodies (moabs), is a noninvasive test system for the analysis and monitoring of renal injury. New moabs allowing an immunohistologic dissection of the human nephron were generated by a direct intrasplenic immunization of mice with pathologic urine samples. A sandwich enzyme immunoassay was developed to quantitate renal cell membrane antigens in the urine samples. A sandwich enzyme immunoassay was developed to quantitate renal cell membrane antigens in the urine. While antigen excretion in healthy individuals is low, preliminary data of a clinical investigation suggest the usefulness of these assay systems in diagnosis of tubular injury in human kidney transplant recipients. The immunoassay can provide very early hints of renal graft rejection prior to the appearance of clinical symptoms or the detection by routine clinical laboratory investigations. PMID- 1758526 TI - Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy. AB - Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved. PMID- 1758527 TI - Treatment of azotemic, nonoliguric, anemic patients with human recombinant erythropoietin raises whole-blood viscosity proportional to hematocrit. AB - It has been reported that patients with azotemia have reduced red blood cell (RBC) deformability. Since this is a major determinant of whole-blood viscosity (WBV) and rigid RBCs increase WBV disproportionately relative to the level of hematocrit, it is conceivable that sustained improvement of hematocrit with recombinant human erythropoietin (rhEPO) therapy in azotemic patients might result in abnormally raised WBV. To address this concern, WBV and plasma viscosity (PV) were measured in 9 adult patients (4 men, 5 women) with anemia (mean hematocrit 29.2 +/- 2.7%) and azotemia [mean serum creatinine concentration 339.85 +/- 102.44 mumol/l (3.8 +/- 1.1 mg/dl)] before and after 6 months of treatment with rhEPO (50-175 U/kg given intravenously thrice weekly). Baseline and post-treatment hematocrit, WBV and PV were compared to values derived in 50 normal adult subjects with normal renal function [25 women, 25 men; mean serum creatinine concentration 79.56 +/- 8.84 mumol/l (0.9 +/- 0.1 mg/dl), mean hematocrit 42.4 +/- 3.7%]. To compare rheologic factors at subnormal hematocrits, blood from subjects with normal renal function was diluted with autologous plasma to achieve a range of hematocrits from 20 to 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758528 TI - Pharmacokinetics and dose response after intravenous and subcutaneous administration of recombinant erythropoietin in patients on regular haemodialysis treatment or continuous ambulatory peritoneal dialysis. AB - The pharmacokinetics and dose response of recombinant human erythropoietin (rhEPO), administered intravenously and subcutaneously, were studied in chronic haemodialysis (HD) patients and in patients on chronic ambulatory peritoneal dialysis (CAPD). Furthermore, two products differing in the presence of albumin as preservative were compared. Although the pharmacokinetics differed after intravenous and subcutaneous administration, the dose response was the same. There is no statistically significant difference in the pharmacokinetics between the rhEPO in HD and CAPD, nor had the presence of albumin as preservative an influence on the pharmacokinetics. PMID- 1758529 TI - Ultrastructural studies of the reaction of urate crystals with a cultured renal tubular cell line. AB - Hypotheses concerning the development of uric acid and gouty nephropathy suggest that the initiating disease mechanism involves an interaction between uric acid or monosodium urate monohydrate (MSUM) crystals and renal tubular epithelial cells. We have studied the interaction of these crystals with Madin-Darby canine kidney (MDCK) cells, which exhibit many of the characteristics of cells of the collecting duct epithelium. Addition of MSUM crystals to monolayer cultures of MDCK cells leads to the formation of reaction sites, localised areas which are raised above the monolayer forming a 3-dimensional structure. These reaction sites are evident within 4-8 h and appear to be initiated by the interaction of a single crystal or small number of crystals with a single cell. With time, both cells and crystals accumulate at the site. By 24 h most reaction sites involve 6 12 cells and numerous crystals. Interaction of MSUM crystals and MDCK cells not only involves the attachment of crystals to cells but, by 8 h, some crystals appear to be completely or partially covered by the cell membrane, and MDCK cells appear to react by growing around the crystals. Transmission electron microscopy shows that crystals are found not only within cells, but also within the intercellular spaces. Within the cells, crystals have been shown in vacuoles containing lysosomal enzymes, indicating the formation of a phagolysosome. Ultimately, enzyme release occurs. These studies support the hypothesis that some interstitial deposits of urate and uric acid in the kidney may be derived from intratubular deposits that react with the tubular epithelium and pass into the interstitium; loss of tubular integrity may not be a prerequisite for crystal migration. PMID- 1758530 TI - Deterioration of immune complex solubilization activity of serum by increased concentration of factor D. AB - We investigated the effect of excess complement factor D on the immune complex solubilization activity (ICSA) of serum. First, we estimated the concentration of factor D, ICSA and the hemolytic activity via the classical complement pathway (CH50) in the sera of 16 healthy individuals and 36 patients on hemodialysis for end-stage renal failure. The serum concentration of factor D in these patients (mean +/- SD: 12.12 +/- 2.38 micrograms/ml) was significantly higher (p less than 0.001) than that in the healthy subjects (1.02 +/- 0.11 micrograms/ml). In this study, peroxidase and antiperoxidase rabbit IgG were used as immune precipitates for ICSA. The ICSA in patients (45.8 +/- 7.4 normal human serum %, NHS%) was significantly lower (p less than 0.001) than that in the healthy subjects (100.2 +/- 12.5 NHS%). There was no difference in CH50 between the sera of the patients (31.8 +/- 2.5) and that of the healthy group (32.4 +/- 2.6). Second, we determined that increasing amounts of purified factor D added to fresh serum resulted in a decrease in ICSA. This occurred in the serum of a healthy individual as well as in that of a patient. CH50 did not change regardless of the concentration of factor D used. There was an increase in C3 conversion in the sera to which purified factor D had been added, as observed by crossed immunoelectrophoresis. It is suggested that ICSA had deteriorated due to the excess of factor D, which had activated the alternative pathway of complement. PMID- 1758531 TI - Urinary albumin excretion in normal pregnancy and pregnancy-induced hypertension. AB - We measured the urinary excretion of albumin in 67 healthy primigravidae, at monthly intervals, from 16 to 36 weeks of gestation and 12 weeks postpartum. Of the 67 primigravidae, 55 completed a normal pregnancy and 12 developed pregnancy induced hypertension. In the latter group, an additional measurement of urinary albumin excretion was performed at 24 weeks postpartum. The aims of the study were: to look for changes of urinary albumin excretion during the progression of normal pregnancy; to assess if microalbuminuria could be an early feature of pregnancy-induced hypertension; to evaluate the effects of physical activity on the excretion of albumin in normal pregnancy and pregnancy-induced hypertension. In contrast with glomerular hyperfiltration and increased urinary total protein, two recognized characteristics of the pregnant state, we found that normal primigravidae, during the day, excrete significantly less albumin (p between less than 0.01 and less than 0.001) in comparison with the postpartum period and nonpregnant women. Normal primigravidae, as a group, showed parallel changes of urinary albumin excretion and diastolic blood pressure throughout pregnancy and postpartum, suggesting an important physiologic role of hemodynamic factors in regulating glomerular permeability to albumin. The daytime urinary albumin excretion in patients developing pregnancy-induced hypertension was significantly higher (p between less than 0.005 and less than 0.001) than in normal pregnancy from the 28th gestational week onwards. The increased urinary albumin excretion preceded the onset of hypertension and tended to persist long after blood pressure had returned to normal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758532 TI - Hyperlipidemia in stable renal transplant recipients. AB - Hyperlipidemia is a major risk factor for atherosclerosis and probably contributes to the increased cardiovascular mortality following renal transplantation. We studied the lipid profiles of 62 adults (29 males) with stable renal function (mean plasma creatinine 0.14 mmol/l, SD 0.07), 7 months to 21 years after renal transplantation. Fifteen patients (24%) were above the age- and sex-adjusted 95th percentile for total triglyceride and 10 (16%) for total cholesterol concentrations when compared with a local reference population. The most common lipoprotein abnormalities were type IIa (19%) and type IIb (13%). Multiple regression analysis demonstrated that the use of diuretics and angiotensin-converting enzyme inhibitors were significant factors determining plasma triglyceride concentrations. There were significant bivariate associations between plasma triglyceride concentration and duration since transplantation, plasma creatinine concentration and the use of ciclosporin and diuretics. Duration since transplantation and ciclosporin use were significant factors determining lower plasma cholesterol concentrations. The use of ciclosporin and diuretics was associated with a significantly higher apolipoprotein (apo) B concentration. The cholesterol/HDL cholesterol risk ratio correlated poorly with the apo B/apo A-1 ratio. The value of these ratios as predictors of coronary artery disease need to be established in renal transplant recipients. PMID- 1758533 TI - Osteocalcin levels in uremic patients: influence of calcitriol treatment through two different routes and type of dialysis. AB - Osteocalcin, the most abundant non-collagen protein of bone, is synthesized by the osteoblast. Serum osteocalcin concentration depends primarily on new cellular synthesis, and is a sensitive marker of bone turnover reflecting osteoblastic function. In uremic and hemodialysis (HD) patients, a direct relationship between serum osteocalcin and histological parameters of bone formation has been observed. The modality of dialysis may influence serum osteocalcin levels though the available data are controversial. The aim of this study is to assess the acute and chronic effects of calcitriol and the influence of modality of dialysis on serum osteocalcin levels. Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were treated with calcitriol. For control purposes, 24 patients, 12 on CAPD and 12 on HD, not treated with calcitriol serum osteocalcin levels were included. In CAPD patients previously treated with calcitriol, serum osteocalcin levels were higher than in nontreated patients. The higher levels occur independent of serum levels of parathyroid hormone (PTH), Ca and P. Hemodialysis patients had osteocalcin levels similar to those of CAPD patients under calcitriol treatment. However, the levels of HD patients were higher than CAPD nontreated patients. Serum ionized Ca was similar in CAPD and HD nontreated patients; however, total Ca was significantly higher in HD than in CAPD patients, both with and without calcitriol. After the intravenous administration of calcitriol, serum osteocalcin levels increased from 9.2 + 2.5 to 13.5 + 5.4 ng/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758534 TI - 1,25-Dihydroxycholecalciferol and peritoneal macrophage chemotaxis in patients on continuous ambulatory peritoneal dialysis. AB - Single graded doses of 1,25-dihydroxycholecalciferol of 2 and 4 micrograms were added intraperitoneally into the overnight 1.5% glucose dialysate of 6 patients on continuous ambulatory peritoneal dialysis. The effect on peritoneal macrophage chemotaxis and random migration was studied and compared with the baseline when no 1,25-(OH)2D3 was added. No consistent effect on peritoneal macrophage chemotaxis was observed. Random migration was significantly depressed at 4 micrograms when compared with baseline (5.4 +/- 1.9 vs. 12.2 +/- 3.7 cells/high power field, p less than 0.05). The potential clinical role of 1,25-(OH)2D3 as an immune modulator requires further study. PMID- 1758535 TI - Serum Tamm-Horsfall glycoprotein level in children with various renal diseases. AB - Serum Tamm-Horsfall glycoprotein (THGP) concentrations were measured by a competitive enzyme-linked immunosorbent assay using peroxidase-labeled THGP in 168 patients, aged 10.5 +/- 4.6 years, with various renal diseases. Using this method, THGP was determined in the concentration range of 10-10(3) micrograms/l. Serum THGP levels ranged from 130 to 350 micrograms/l in 32 control subjects, aged 1-16 years with normal renal function. In most patients with renal disease, the serum THGP levels were lower than those in control subjects. In particular, the serum THGP levels were more reduced according to the decrease in the clearance values of endogenous creatinine (CCR). These findings suggested that the measurement of serum THGP levels is helpful in the evaluation of renal function. On the other hand, 3 patients with vesicoureteric reflux showed higher serum THGP levels than control subjects, though the CCR values in 1 of these patients was lower. These high serum THGP levels may be the result of urinary backflow into circulation. PMID- 1758536 TI - Adverse effects on cerebral perfusion of prostacyclin administered directly into patients with fulminant hepatic failure and acute renal failure. AB - Prior to commencing renal replacement therapy, 8 patients with fulminant hepatic failure and acute renal failure were treated with an infusion of prostacyclin, 5 ng/kg/min, for 30 min, administered directly into the femoral vein. During this period, several adverse effects were noted. There was a reduction in mean arterial blood pressure from a median of 82 (range 65-93) to 67 mm Hg (55-80), p less than 0.01; and an increase in intracranial pressure from a median of 14 (6 33) to 17 mm Hg (6-42), p less than 0.05; with a consequent reduction in cerebral perfusion pressure from a median of 63 (43-77) to 43 mm Hg (15-74), p less than 0.05. There was a reduction in arterial oxygen tension from a median of 19 (13 28) to 16 kPa (12-27), p less than 0.05; and no change in cardiac output, from a median of 6.7 (4.9-11.2) to 6.5 l/min/m2 (3.8-11.0), p greater than 0.05). The administration of prostacyclin into this group of critically ill patients, at risk of death due to cerebral oedema/hypoxia, produced both a reduction in cerebral perfusion pressure and a reduction in total cerebral oxygen delivery. PMID- 1758537 TI - Increases in circulating level of platelet-activating factor lag behind transient neutropenia during hemodialysis with cuprophane membranes. AB - The significance of the level of circulating 1-O-hexadecyl-2-acetyl-sn-glycero-3 phosphorylcholine (C16-PAF, platelet-activating factor) in relation to transient neutropenia during hemodialysis with cuprophane membranes was examined. The neutrophil count was transiently and significantly decreased at 30 min after the start of hemodialysis, and it then gradually recovered during the period from 60 to 240 min after the start. Mirror image changes were observed in the circulating levels of C3a and C5a, suggesting that the decrease in the neutrophil count was triggered by activation of the complement factors. The circulating level of C16 PAF, although being similar to the basal level after 30 min of hemodialysis, was significantly increased after 60 and 120 min of hemodialysis. These data indicate that the increase in the circulating PAF level is not a direct cause of the transient decrease in the neutrophil count, but may be the result of activated neutrophils during hemodialysis with cuprophane membranes. PMID- 1758538 TI - Hyperlactataemia and metabolic acidosis during haemofiltration using lactate buffered fluids. AB - We have investigated the effect of an exogenous lactate load given during machine haemofiltration treatment in 22 patients with acute renal failure and 12 patients with chronic renal failure, without any overt evidence of liver disease. Hyperlactataemia occurred in all patients, but the expected changes in acid base status, an increase in bicarbonate and a reduction in arterial hydrogen ions were observed in less than 40% of the treatments in the acute renal failure group. Ultrafiltrate losses of lactate and bicarbonate could not alone explain the changes in acid-base status. There was a positive correlation between the increase in arterial lactate and hydrogen ion concentrations, r = 0.52, p less than 0.01. Lactate accumulation in patients at, or close to, their threshold for lactate utilisation may result in further depression of cardiac function and peripheral lactate utilisation. Hyperlactataemia due to use of lactate-based dialysis/haemofiltration solutions in critically ill patients may result in a worsening of the acid-base status, and arterial pH should be monitored so that bicarbonate solutions can be substituted if the changes are progressive. PMID- 1758539 TI - Selective hypoaldosteronism in a patient with Sjogren's syndrome: insensitivity to angiotensin II. AB - A 51-year-old Japanese woman with hypokalemia due to distal renal tubular acidosis associated with Sjogren's syndrome exhibited a decreased plasma aldosterone level despite elevated plasma renin activity. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid function. In the presence of a low level of serum potassium (3.6 mEq/l), plasma levels of deoxycorticosterone and corticosterone were normal, while plasma aldosterone was very low. The levels of these three mineralocorticoids showed only minor changes during infusion of angiotensin II. Furosemide administration under almost the same level of serum potassium (3.7 mEq/l) resulted in only a slight increase of plasma aldosterone. Since hypokalemia might possibly suppress the synthesis of aldosterone in the zona glomerulosa, angiotensin II was also infused under a normal level of potassium (4.3 mEq/l). However, angiotensin II also failed to stimulate any secretion of aldosterone, despite a progressive rise in blood pressure and sufficient suppression of plasma renin activity. On the other hand, rapid ACTH administration in the presence of 4.4 mEq/l of serum potassium increased both plasma aldosterone and cortisol. These results suggest that adrenal insensitivity to angiotensin II was the cause of the selective hypoaldosteronism in our patient, possibly due to a dysfunction of adrenal angiotensin II receptors, a disorder of postreceptors or both. PMID- 1758540 TI - Renal lesions of hyperlipidemic Imai rats: a spontaneous animal model of focal glomerulosclerosis. AB - The hyperlipidemic Imai rat was originally developed as an animal model of spontaneous hyperlipidemia. We report the natural course of the Imai rat up to 32 weeks of age focusing on renal pathology. The degree of proteinuria, which first appeared at 8 weeks, increased with age, and all Imai rats developed heavy proteinuria (mean, 228 mg/24 h) with impaired renal function (mean BUN, 78.7 mg/dl) at 32 weeks. Histologic changes of the glomeruli were characterized by focal and segmental sclerosis and hyalinosis. Both the percentage of affected glomeruli and the severity of each affected glomerulus were progressively increased with age. The immunofluorescence and electron-microscopic findings were also comparable to those of focal glomerulosclerosis (FGS) in humans. The serum levels of total cholesterol, triglyceride, and phospholipid in Imai rats were significantly higher than those in normal Sprague-Dawley rats at 8 weeks of age, and progressively increased thereafter. The proteinuria, glomerular involvements, and hyperlipidemia were generally less severe in the females than in the males. We conclude that the hyperlipidemic Imai rat, a naturally occurring animal model of FGS, is useful in studying the pathogenesis of FGS and the renal effects of hyperlipidemia in humans. PMID- 1758541 TI - Effects of defibrotide on renal function and urinary prostanoid excretion in ciclosporin-treated rats. AB - Defibrotide (DF) has been proposed as a new antithrombotic agent in renal transplantation. Because it was also found to increase prostacyclin synthesis, a reduction in ciclosporin (CS) nephrotoxicity could be supposed. To ascertain this hypothesis, renal function and urinary prostanoids were evaluated in four groups of rats after 10 days of oral treatment (doses in mg/kg/day): CS 50 (group A), CS 50 + DF 400 (group B), DF 400 (group C) and controls (group D). Compared to controls, creatinine clearance (CCR) was significantly lower in groups A and B (In CCr: A = 6.62 +/- 0.28, B = 6.83 +/- 0.24 vs. 8.17 +/- 0.13 microliters/min, p less than 0.01), whereas it did not change in group C (8.03 +/- 0.24 microliters/min). The urinary excretion of prostaglandin E2 (PGE2) was significantly (p less than 0.05) higher in group A (In PGE2: 3.98 +/- 0.98 nmol/mol Cr) and more evidently in groups B and C (6.89 +/- 0.38 and 6.01 +/- 0.32 nmol/mol Cr, respectively) compared to controls (1.43 +/- 0.45 nmol/mol Cr). The urinary excretion of 6-keto-PGF1 alpha and of thromboxane B2 (TxB2) were higher only in groups A and B (ln 6-keto-PGF1 alpha and ln TxB2: A = 6.45 +/- 0.22 and 4.97 +/- 0.20, B = 7.06 +/- 0.31 and 5.43 +/- 0.41 vs. group D = 5.53 +/ 0.22 and 3.79 +/- 0.42 nmol/mol Cr; p less than 0.05). The 6-keto-PGF1 alpha/Tx molar ratio was not significantly affected, although a trend for a reduction in the ratio was found in the treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758542 TI - Renal allograft arteriovenous fistula due to needle biopsy with late onset of symptoms--diagnosis and treatment. AB - A post-biopsy arteriovenous (AV) fistula in a renal allograft was diagnosed using color-coded Doppler sonography. Because the patient was asymptomatic, no specific treatment was initiated. 15 months after the diagnosis was established, severe hematuria with obstruction of the bladder occurred. Angiography revealed a connection of the fistula to the renal pelvis. The patient was treated successfully by transarterial embolization of the fistula. As a conclusion, we suggest periodical follow-up examinations of asymptomatic AV fistulas in renal allografts using color-coded Doppler sonography during 3-6 months. When no spontaneous regression of the fistula can be observed, embolization therapy should be performed even when the fistula is asymptomatic, in order to prevent late onset of complications. PMID- 1758543 TI - Recurrence of IgA nephropathy with nephrotic syndrome after kidney transplantation. AB - Two patients on maintenance hemodialysis after terminal renal failure due to mesangial glomerulonephritis with IgA deposits and the nephrotic syndrome, received cadaver renal allografts. After several years of functioning transplants, both patients developed slowly progressive proteinuria and finally the nephrotic syndrome, 1 of them with renal function deterioration. Renal biopsies revealed findings indicating recurrence of the original disease. PMID- 1758544 TI - Sudden blindness associated with central nervous symptoms in a hemodialysis patient. AB - Purtscher's-like retinopathy as a cause of sudden blindness in hemodialysis patients is not widely known. This is believed to occur secondary to leukoembolization to retinal arterioles following complement activation. We describe a patient who developed sudden but reversible loss of vision on hemodialysis associated with varying reversible neurological signs and symptoms which we felt may have been a manifestation of leukoembolic aggregates lodging in the arterioles of the retina and central nervous system circulations. PMID- 1758545 TI - Hemolytic-uremic syndrome with anticardiolipin antibodies revealing paraneoplastic systemic scleroderma. AB - Lupus anticoagulant was present in this case of paraneoplastic scleroderma revealed by hemolytic-uremic syndrome, suggesting that the autoantibody played a significant role in the sequence of events leading to anuria. Reviewing the literature we found several observations of paraneoplastic scleroderma, and in other series cases of scleroderma-linked (and in rare instances cancer-linked) antiphospholipid autoantibodies. Search for antiphospholipid antibodies should be considered in patients with systemic scleroderma as well as in patients with metastatic cancer. Presence of such procoagulant autoantibodies might predict future complications and should influence treatment strategy. PMID- 1758546 TI - Anaphylaxis following intravenous methylprednisolone sodium succinate in a renal transplant recipient. PMID- 1758547 TI - Lymphocytotoxic panel reactive antibodies in hemodialyzed patients treated with recombinant human erythropoietin. PMID- 1758548 TI - Recovery of anionic sites of the glomerular basement membrane after their disappearance by the cationic probe molecule. PMID- 1758549 TI - Aluminum and parathyroid hormone concentrations in insulin-dependent diabetics on long-term hemodialysis. PMID- 1758550 TI - Prostatic cancer in a patient on long-term hemodialysis. PMID- 1758551 TI - Peritoneal dialysis induces a local sterile inflammatory state and the mesothelial cells in the effluent are related to the bacterial peritonitis incidence. PMID- 1758553 TI - False positive auto-antibodies in HIV infection. PMID- 1758552 TI - Systemic amyloidosis (type AA) in end-stage renal failure patients due to chronic pyelonephritis. PMID- 1758554 TI - Thrombolysis of blocked hemodialysis catheter using recombinant tissue-type plasminogen activator. PMID- 1758555 TI - Absence of anaphylactoid reactions with the combined use of ACE inhibitors and AN69 hemodialysis membranes. PMID- 1758556 TI - Elevated plasma concentration of arginine-vasopressin in renal insufficiency is not caused by nonspecific binding of metabolic breakdown products. PMID- 1758557 TI - Relating change to initial value. PMID- 1758558 TI - Aluminum toxicity from oral sucralfate therapy. PMID- 1758559 TI - Systemic amyloidosis secondary to tumoral calcinosis. PMID- 1758560 TI - Incidence of atopy in IgA nephropathy. PMID- 1758561 TI - Review of experimental spinal cord injury with emphasis on the local and systemic circulatory effects. AB - Studies of experimental spinal cord injury began approximately 100 years ago, and since then many useful models of acute experimental spinal cord injury have been developed which stimulate many of the common types injuries in man. This review will describe some of these models and the information they have provided about the acute pathophysiological mechanisms in the injured spinal cord. There is good experimental evidence that the spinal cord suffers both a primary or mechanical injury and then a secondary injury which may worsen the prognosis for recovery. This review will emphasize the concept of the secondary injury, especially with respect to the vascular mechanisms. There is evidence from our laboratory and others to support the concept of the secondary injury and that the chief mechanism of the secondary injury is posttraumatic ischemia and infarction of the spinal cord. We have found evidence for the role of vascular mechanisms in three different injury models of acute spinal cord injury (A.S.C.I.) in three species of experimental animals. This review will describe the microangiographic and blood flow methods for assessing the microcirculation of the spinal cord after trauma. In addition, to these local vascular effects, this review will also describe the systemic vascular effects of A.S.C.I. which cause the neurogenic shock in this condition. It is our hypothesis that these local and systemic vascular effects are principal causes of the secondary injury leading to posttraumatic ischemia and infarction of the spinal cord after A.S.C.I. Furthermore, it is our hypothesis that early treatment of these microcirculatory changes and neurogenic shock can lead to improved recovery after A.S.C.I. PMID- 1758562 TI - [Reconstruction of the spinal cord and its motor connections using embryonal nervous tissue transplantation and peripheral nerve autotransplantation. A study in the adult rat]. AB - Our research group is studying, in the adult rat, the conditions of an anatomical and functional reconstruction of the spinal cord and of its motor connections, following a spinal lesion that is either small (focal) or large (depletive). In this attempt to repair the damaged neuronal circuitry, we use, alone on in combination, two transplantation techniques, namely that of embryonic neural tissue, to replace the lost neurons, and that of long segments of autologous peripheral nerves to stimulate and guide either the axonal regrowth from injured host spinal neurons or the axogenesis of transplanted embryonic neurons. The common denominator to the whole experimentation is the setting up of a "nerve bridge" (peroneal nerve autograft) joining the injured cervical spinal cord an aneural region of a nearby denervated skeletal muscle. In a first experimental model (focal lesion), in which only a peripheral nerve autograft is used, it can be observed that local injured (or uninjured?) motoneurons have the actual capacity to extend axons throughout the nerve bridge and, thus, to reach the muscle and reform functional and stable, mainly ectopic, neuromuscular connections. In a second experimental model (depletion lesion) a cavity is made, by suction, in the cervical spinal cord, thus causing a damage which resembles, in some respects, certain types of neurodegenerative spinal lesions. This cavity is filled with different kinds of embryonic neural transplants. The surviving transplanted neurons differentiate axonal projections, some of them extending into the peripheral nerve bridge. Studies aimed at determining the capacities of motor endplate formation by the axons that have grown from these neurons of substitution throughout the nerve bridge, as well as the possibilities of reafferentiation of the transplanted tissues by regenerating host "central" nerve fibres, are in progress. PMID- 1758563 TI - [Traumatic atlanto-occipital dislocation]. AB - Traumatic atloido-occipital dislocation is usually fatal with immediate cardio respiratory arrest. The authors report 3 cases of children who survived such a spine injury despite neurological impairment. Clinical and radiological data including Magnetic Resonance Imaging are compared with 18 other cases reported in the literature. PMID- 1758564 TI - [Value of the measurement of cerebral blood flow before and after diamox injection in predicting clinical vasospasm and final outcome in aneurysmal subarachnoid hemorrhage]. AB - The timing for surgery on ruptured intracranial aneurysms remains a difficult question and the choice of the day of operation depends greatly from the occurrence of a vasospasm. On a previous paper, the value of the cerebral blood flow (CBF) measurement by intravenous injection of Xenon 133 was demonstrated to be efficient for the prediction of vasospasm only when done between day 4 and day 8 after bleeding. Moreover the efficiency of the measurement was much greater if the evolution of the CBF values between D0 and D8 was considered, but this method was incompatible with early surgery. It suggested the interest of a dynamic study of the CBF by the same method. On a series of 43 patients, the comparison between basal CBF values and reactivity of CBF values to intravenous injection of 1 gram of acetazolamide for the prediction of clinical vasospasm is presented. The series comprises 32 early admitted patients (74%) and 31 operated patients (16 of them between D0 and D3 after bleeding, 15 others after D4). The efficiency of the CBF reactivity study for the prediction of the clinical vasospasm appears much greater than that of the basal CBF value, even during the first three days after bleeding, but not for the prediction of the final clinical outcome. The method is immediate and compatible with early surgery. What precisely is evaluated by this method on the physiopathology of the vasospasm remains disputable, but the operability of the patients seems to be explored. PMID- 1758565 TI - [Peroperative monitoring of early auditory evoked potentials in microsurgical vascular decompression for trigeminal neuralgia or hemifacial spasm]. AB - Intra-operative B.A.E.P. monitoring have been performed in two series of patients who underwent Microsurgical Vascular Decompression (M.V.D.) of the Vth and VIIth cranial nerves in the posterior fossa. The first series consisted of 17 patients among the 400 operated on for Trigeminal Neuralgia (T.N.), the second one also of 17 patients among the 25 treated for Hemifacial spasm (H.S.), over the last four years. The equal number of recorded patients in the two groups is totally fortuitous. The aim of the work was to correlate the electrophysiological changes: 1) to the surgical manoeuvres potentially responsible for B.A.E.P. alterations, in order to modify the M.V.D. technique, so as to minimize the risks of hearing loss, 2) to the eventual post-operative auditory disturbances, in order to define prognostic criteria from B.A.E.P. monitoring. I. Intra-operative B.A.E.P. modifications were graded into 4 categories, according to their degree of severity (table II): minimal changes (category 1), increase in latency returning to normal (2) or without normalization (2a) before end of surgery, abolition or partial decrease of responses returning to normal (3) or without complete normalization (3a) before end of surgery, total B.A.E.P. loss lasting through the entire procedure (4). Patients operated on for H.S. had more often significant B.A.E.P. changes than those with T.N., respectively 10 and 6 for categories 3a and 4 together. Auditory function was at risk mainly during cerebellar retraction (especially if cerebello-pontine angle was approached laterally) and during vascular manipulation of the labyrinthine artery (which can generat vasospasm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758566 TI - [Suprasellar tumors in patients over 70 years of age. Value of limited frontotemporal craniotomy. Visual results. Apropos of 5 cases]. AB - The authors report their experience of the surgical approach for suprasellar tumors (Jugum or tuberculum sellae meningiomas, 3 cases, and suprasellar craniopharyngiomas, 2 cases) in over than seventy years old patients (71-78 y). A limited craniectomy was performed at the fronto-temporal junction using three adjacent burr-holes. The duramater was cut with an Y-shaped incision. Cerebrospinal fluid was sucked out through a lateral subfrontal route, allowing an easy cerebral collapse in elderly patients, which can sometimes avoid even retraction. Such an supra-orbital craniectomy allowed a subfrontal approach, opening of the sylvian fissure and control of the inter optic, inter carotido optic and latero-carotidian spaces as well as a good access to the inter pedoncular cistern. In 4 cases the craniectomy was performed after fronto temporal skin incision, but a trans eyebrow skin incision was used in 1 case. All patients had uneventful postoperative course. Follow-up was from 3 to 5 years. A visual improvement occurred in all cases. Benefits of this surgical method are discussed and compared with use of a bone flap in patients over than 70 years. PMID- 1758567 TI - [Paraganglioma of the cranial vault. Apropos of a case]. AB - The authors report the case of a 40 years old woman with a fronto parietal tumefaction and intracranial hypertension caused by a paraganglioma of the cranial vault. The clinical follow up is marked by rapid local recurrence of the tumor after complete excision. Usually paragangliomas arise in any area of the body where paraganglionar structures are situated (glomus jugulare, carotid glomus, vagus nerve). Other rare locations have been reported and remain difficult to be explained. The location at the cranial vault is exceptional. this tumor would probably arise from the paraganglionar cells which migrate from the neural crest following the trigeminal branches particularly the ophtalmic division. PMID- 1758568 TI - Animal models of muscular dystrophy--what can they teach us? AB - The discovery and characterization of the X-linked gene which is defective in Duchenne muscular dystrophy (DMD) and of its protein product, dystrophin, has led to the identification of biochemical homologues of this disease in the mouse, the dog and the cat. All three animal models resemble DMD in that they lack dystrophin and that their skeletal muscle fibres undergo spontaneous necrosis and regeneration. In the dog and man, the degenerative and fibrotic aspects predominate, leading to a progressive loss of muscle structure and function, and to severe clinical disability. By contrast, in the mouse and the cat there is little fibrosis and the regenerative process seems to overcompensate, producing a true muscle hypertrophy and little or no clinical deficit. This interspecies variation in pathological response limits the usefulness of these animals as models for therapeutic testing, calling into question the strength of linkage between a given biochemical lesion and a particular pattern of pathology. However, these differences do give a valuable perspective to the pathology of the dystrophin-deficiency diseases, permitting identification of the immediate and secondary consequences of the lack of dystrophin. Moreover, the dystrophic mouse and dog are readily bred as colonies, thus providing consistent material for investigating the function of dystrophin and for testing methods of replacing its function or compensating for the absence of this function in the muscles of DMD patients. The fact that a lack of dystrophin is compatible, in some species, with only minor muscle dysfunction, raises hopes for an effective therapy in man. PMID- 1758569 TI - Demonstration of beta amyloid protein-containing neurofibrillary tangles in parkinsonism-dementia complex on Guam. AB - This report concerns the immunohistochemical demonstration of beta amyloid protein-containing neurofibrillary tangles (beta-NFTs) from patients with parkinsonism-dementia complex on Guam (PDC). Formalin-fixed paraffin-embedded tissue sections from the temporal lobe of nine PDC cases and the spinal cord of three were examined. An affinity-purified antibody to the N-terminal peptide sequence of beta amyloid protein was used. beta-NFTs were demonstrated in the temporal lobes of the three oldest individuals. Some senile plaques, probably a manifestation of ageing, were also seen. The beta-NFTs were most frequent in the entorhinal cortex. Senile plaques were invariably present in the vicinity of the beta-NFTs. Conversely, in the regions without senile plaques, even though numerous neurofibrillary tangles were identifiable with the modified Bielschowsky method, no beta-NFTs were seen. The density of beta-NFTs appeared to be proportional to that of senile plaques, none was seen in cases lacking senile plaques. No beta-NFTs were detected in the spinal cords. Our data suggest that beta-NFTs result from secondary beta amyloid deposition on certain neurofibrillary tangles. PMID- 1758570 TI - An immunohistological study of macrophages in the human fetal brain. AB - Brains from human fetuses of 13 to 27 weeks gestation have been examined immunohistologically for the presence of macrophages using the marker alpha-1 anti-chymotrypsin. A preliminary study demonstrated this to be a satisfactory marker of brain macrophages, although macrophages were also weakly positive for the more specific marker MAC-387. Macrophages were widely present within the cerebral hemispheres following their rapid accumulation between 14 and 16 weeks of gestation. They were identified in characteristic locations which, in the earliest gestation brains examined at 13 weeks, included the mid-line of the corpus callosum, around the optic tract and at the junction of the external and internal capsules near the apex of the putamen. Subsequently, macrophages were identified in abundance in the internal and external capsules and, by 22 weeks gestation, in the periventricular tissues. Their consistent presence and distribution indicate that at least the majority of these macrophages are a normal feature of the developing brain possibly related to remodelling processes. PMID- 1758571 TI - The glial reaction in closed head injuries. AB - The development of the glial reaction in human closed head injury has been investigated using morphometry and statistical analysis. The brains of eight individuals that survived less than 48 h following closed head injury were analysed using immunoperoxidase for glial fibrillary acidic protein (GFAP). Controls were eight patients without neurological disease. The density of reactive astrocytes was estimated in 25 fields in each of 10 different areas sampled bilaterally avoiding the subpial and subependymal zones, and the perivascular white matter. There was great variation between the zones within and between groups, and considerable variation between individuals. The raw data were expressed as logarithms averaged and analysed using the median and non-parametric statistics. The corpus callosum in the head injury group showed the highest densities of reactive astrocytes, particularly in the splenium which achieved statistical significance using the non-parametric tests. This pattern was not reproduced in the control group. Although there was overlap between the head injured and control individuals, the head injury group had relatively higher densities in all zones, and showed an overall increase in the density of reactive astrocytes. This achieved statistical significance in the corpus callosum, the occipital subcortical white matter, and the cerebellum. This study has shown that the glial reaction is often prominent in the corpus callosum irrespective of the presence of a primary lesion although the pattern varies from case to case. PMID- 1758572 TI - A method to quantitate axonal injury. AB - The quantitation of diffuse axonal injury provides a more objective approach to the assessment of tissue damage in head injuries. The method designed in this study takes into account the anisotropy and structural inhomogeneity of the brain, and the distribution of lesions in diffuse axonal injury. The number of counts required for the statistical analysis is inversely proportional to the square of the desired accuracy, specified as the percentage of the mean value of the axonal balloons since the true mean is unknown from the outset. The number of fields are examined using an indexed-squares graticule in 10 different areas of the brain. Silver-stained sections from the brains of head injured patients that survived longer than 12 h must be used with this method. Difficulties may arise when patients of different survival times are compared since it takes some time for the axonal balloons to develop. A correlation with the survival time can be established with the quantitative data collected. The morphometric principles and the statistical rationale on which this methodology is based are briefly presented. PMID- 1758573 TI - Acute inhibition of pituitary LH release in the male rat by the glucocorticoid agonist decadron phosphate. AB - The present study was carried out to investigate the effects of acute administration of the soluble glucocorticoid receptor agonist, decadron phosphate (DEC, dexamethasone sodium phosphate), on pituitary luteinizing hormone (LH) release in intact adult male rats. DEC was administered intravenously to individual groups of animals at a dose of either 0.05 or 0.5 mg DEC/kg, and the magnitude and time course of drug-induced alterations in plasma LH concentrations were evaluated. DEC was observed to elicit a dose-proportionate decrease in plasma LH within hours after systemic injection. Both doses of DEC significantly reduced the magnitude of exogenous LH-releasing hormone (RH; 10 ng/100 g b.w.) induced increases in plasma LH at time points coincident with drug-induced decreases in basal LH release. During in vitro perifusion of isolated anterior pituitary tissue fragments, the administration of DEC, via the perifusate, at a concentration of 1.0 microgram/ml had no impact upon basal LH release, but did effectively diminish LHRH-stimulated hormone release from perifused tissues. Intracerebroventricular injection of DEC also resulted in a decline in circulating LH. While intracerebroventricular (ICV) administration of 10 ng of DEC had no impact upon circulating LH, higher doses of 100 ng and 1.0 micrograms significantly depressed circulating LH levels in a dose-related manner. Both of these ICV doses were also found to diminish pituitary responsiveness to LHRH. Lastly, DEC was intravenously administered at a dose of 0.5 mg/kg to groups of orchidectomized and orchidectomized, testosterone (T)-treated male rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758574 TI - Interactions between the noradrenergic and opioid peptidergic systems in controlling the electrical activity of luteinizing hormone-releasing hormone pulse generator in ovariectomized rats. AB - The effects of noradrenergic and opioid peptidergic receptor blockade, either alone or in combination, on the electrical activity of luteinizing hormone releasing hormone (LHRH) pulse generator were studied in ovariectomized rats fitted with chronically implanted electrode arrays in the medial basal hypothalamus. Both alpha- and beta-adrenergic receptor antagonists, i.e. phenoxybenzamine (5 mg/kg i.v.) and propranolol (5 mg/kg i.v.), respectively, significantly increased the intervals between characteristic increases (volleys) in hypothalamic multiunit activity (MUA), which were associated with the initiation of LH pulses. In contrast to this, an opioid receptor antagonist naloxone (2 mg/kg i.v.) significantly decreased the intervals between the MUA volleys. Naloxone given after the injection of propranolol induced MUA volleys with a latency of a few minutes. However, when given after the injection of phenoxybenzamine, naloxone failed to induce such immediate MUA volleys. These changes in the intervals between the MUA volleys were faithfully reflected by the pulsatile LH secretion. These results suggest that norepinephrine facilitates LHRH pulse generator activity through both alpha- and beta-adrenergic-receptors, and that the action of opioid peptides on it requires an alpha-adrenergic receptor-mediated mechanism. PMID- 1758575 TI - Maintenance of LHRH and oxytocin neurons in slice explants cultured in serum-free media: effects of tetrodotoxin on gene expression. AB - A variety of neuroendocrine cells survive and express specific neuropeptide genes for long periods of time in slice explant cultures in the presence of serum. However, before use of these slice explant cultures as experimental models for physiological and pharmacological studies on the regulation of neuropeptide gene expression, it is first necessary to evaluate their characteristics in defined (e.g. serum free) media and to control for the spontaneous electrical and synaptic activity of neurons in these cultures. In this study, brain slices from postnatal day 4 rats were cultured in serum-containing media (SCM) for 12 days to allow thinning, and then maintained in a serum-free, defined media (SFM) for 6 days. Culture slices transferred to SFM appeared healthy and numerous neuroendocrine neurons containing messenger RNA (mRNA) encoding for LHRH and magnocellular neurons containing mRNA encoding for oxytocin (OT) were detected using in situ hybridization histochemistry (ISHH). Each of these neuronal subtypes robustly produced their appropriate gene products as determined by immunocytochemical analysis. Abundant magnocellular OT neurons were found in cultures grown in either SCM or SFM. In contrast, magnocellular vasopressin (VP) neurons were rarely detected under these conditions. Inhibition of spontaneous electrical and synaptic activity in these slice explant cultures was effectively achieved by incubation for the last 2.5 days of culture in the presence of tetrodotoxin (TTX; 10(-6) M). Densitometric single cell analyses after ISHH was performed on both LHRH and OT cells. Comparisons of the density values (corresponding to mRNA levels), from these slice explants, found that: (1) cellular LHRH mRNA levels decreased in the absence of serum, whereas cellular OT mRNA levels did not significantly change under these conditions; (2) the presence of TTX in the media resulted in an overall decrease in cellular LHRH mRNA values in both SCM and SFM, and (3) the OT neurons in these slice cultures appear to be composed of a heterogeneous population, with one cell subtype responding to TTX with an increase in cellular OT mRNA levels. These data show that factors in serum and spontaneous electrical activity can differentially influence mRNA levels of LHRH cells and magnocellular OT neurons in culture. PMID- 1758576 TI - Anterograde nerve degeneration after superior cervical ganglionectomy coexists with a decrease in arginine vasopressin release in rats. AB - After bilateral superior cervical ganglionectomy (SCGx) in adult male rats, norepinephrine content of the pituitary neurointermediate lobe (NIL) decreased at 12-24 h after surgery to attain concentrations 40-60% of controls between 24 and 60 h after surgery. To assess arginine vasopressin (AVP) secretion during this time, plasma and NIL-AVP levels were measured by radioimmunoassay. In sham SCGx controls, plasma AVP increased about 2-fold within 6 h after surgery and decreased thereafter, to attain presurgical values by 60 h after surgery. In SCGx rats, a significant increase in plasma AVP concentration was observed at the 6th h after surgery, as compared to presurgical concentrations, with a decrease to values significantly lower than those of presurgical controls at 16-18 h after SCGx. As compared to sham-operated rats, significantly higher plasma AVP levels 6 h after surgery and significantly lower plasma AVP levels 16-24 h after surgery were found. NIL-AVP concentration in SCGx and sham-operated ras were significantly lower than presurgical levels at 6 h after surgery. SCGx rats had significantly higher amounts of AVP in NIL at 16-24 h after surgery. The changes in plasma and NIL-AVP levels found 6 or 16 h after SCGx or sham SCGx were unaffected by a prior pinealectomy. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta blocker propranolol, prevented the increase in plasma AVP found in SCGx rats 6 h after surgery, and the decrease in plasma AVP and the increase of NIL-AVP found 16 h after SCGx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758577 TI - Regulation of hypothalamic gonadotropin-releasing hormone secretion in experimental uremia: in vitro studies. AB - Defective regulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion is the primary defect leading to the inhibition of pituitary gonadotropin secretion and its consequences such as androgen deficiency and infertility in experimental uremia. Previous studies using indirect methods to study presumptive GnRH release and the function of GnRH-secreting neurons have suggested functional disturbances of GnRH neurosecretion; however, the precise biochemical mechanisms involved were not defined. Therefore, in order to clarify the mechanisms of aberrant regulation of hypothalamic GnRH secretion in experimental uremia, we examined basal secretion of GnRH from mediobasal hypothalamus (MBH) in vitro and the GnRH-secretory responses to naloxone, an opiate receptor antagonist in experimental uremia. Using a static incubation system, adult male rats, either intact or castrate, with subtotal nephrectomy demonstrated a significant reduction of GnRH secretion by 25% in intact and by 40% in castrate uremic male rats compared with their nonuremic controls. In contrast, hypothalamic GnRH content of uremic animals was increased significantly (6% in intact and 14% in castrate uremic rats). Despite the fall in basal GnRH release from MBH, the MBH GnRH release response to in vitro stimulation by an opioid blocker (naloxone) and a membrane-depolarizing agent (veratrine) were not diminished in uremic male rats. These findings suggest that the inhibition of pituitary gonadotropin secretion in experimental uremia is likely to be due to a functional defect in suprahypothalamic regulation of GnRH secretion rather than an intrinsic defect in the GnRH-secreting neurons. Further studies are required to clarify the nature of the neuromodulator interactions involved. PMID- 1758578 TI - Estrogen increases spine density in ventromedial hypothalamic neurons of peripubertal rats. AB - Using the single-section Golgi impregnation technique, sex differences in hypothalamic ventromedial (VMN) neurons of gonadectomized juvenile and peripubertal rats were assessed. The effect of estrogen treatment on VMN neurons was also investigated. Juvenile rats were gonadectomized at 16 days of age and peripubertal rats at 36 days. At 5 days after surgery, the rats were injected with estradiol benzoate (20 micrograms/kg) or sesame oil for 2 days after which they were perfused and the brains processed for Golgi impregnation. Estradiol benzoate treatment significantly increased dendritic and soma spine density in juvenile and peripubertal male and female rats. A sex difference was observed in oil- and in estradiol-treated rats, with females exhibiting higher dendritic spine density and a greater response to estrogen priming. Moreover, dendritic and soma spine density was significantly higher in juvenile versus peripubertal rats. It is possible that the sex difference observed in dendritic and soma spine density and in the response to estradiol benzoate treatment is due to an organizational effect of sex steroids. PMID- 1758579 TI - Activin-A modulates gonadotropin-releasing hormone secretion from a gonadotropin releasing hormone-secreting neuronal cell line. AB - The recent development of GnRH-secreting neuronal cell lines (GT1-1, GT1-3 and GT1-7 clones) has provided a model system for the study of the neural regulation of GnRH expression and secretion. We report here that activin-A stimulates GnRH secretion by GT1-7 cells in a dose-dependent manner, with an EC50 of approximately 2.5 ng/ml. The maximal response (50% stimulation) was achieved after 2 days of incubation with 20 ng/ml activin-A. Activin-A treatment increased total GnRH (secreted + cellular) in GT1-7 cells, possibly reflecting a stimulation of GnRH biosynthetic rates. The secretory effect of activin-A was also accompanied by a change in the cellular morphology to a more neuronal phenotype. The addition of TGF-beta (10 ng/ml), which is structurally related to activins, did not significantly increase secretion of GnRH by GT1-7 cells illustrating the specificity of the activin effect on this cell line. Although inhibin (20 ng/ml) alone did not directly affect the spontaneous secretion of GnRH, it was able to partially block the stimulatory effect of activin. The present study with the GT1-7 clonal cell line suggests that activin, and perhaps inhibin, might act at hypothalamic sites to regulate reproduction through the control of GnRH production and/or secretion. PMID- 1758580 TI - Septal and hippocampal release of vasopressin and oxytocin during late pregnancy and parturition in the rat. AB - The push-pull perfusion technique, in conjunction with specific radioimmunoassays, was used to monitor the release of both arginine vasopressin (AVP) and oxytocin (OXT) within distinct limbic brain areas of conscious female rats. In pregnant rats near term, the release of AVP was greater than that of virgin rats in both the ventral (p less than 0.001) and mediolateral (p less than 0.001) septal areas; similarly, release of OXT increased in the ventral septal area (p less than 0.01) at this time. In contrast, no changes in the levels of either peptide occurred in the dorsal hippocampus. In parturient rats, AVP release tended to decrease in the septal areas but increased fivefold in the dorsal hippocampus (p less than 0.001) compared to pregnant animals. In contrast, OXT levels assayed in the same perfusates did not differ from those observed in pregnant animals. Plasma levels of AVP in pregnant rats (p less than 0.05) and of OXT in parturient animals (p less than 0.01) were found to be increased over levels in virgin rats. The regionally different and peptide-specific changes in release pattern of AVP and OXT in virgin, pregnant and parturient rats may be of physiological significance in antipyresis and behaviors accompanying parturition. PMID- 1758581 TI - Stimulation of hypothalamic prolactin release by veratridine and angiotensin II in the female rat: effect of ovariectomy and estradiol administration. AB - In the female rat immunoreactive prolactin (IR-PRL) has been identified in the hypothalamus and in other brain regions. Brain IR-PRL is not of pituitary origin and, based on polyacrylamide gel electrophoresis and peptide mapping, shares a high degree of sequence homology with its pituitary counterpart. We have previously shown that hypothalamic tissue can release IR-PRL in vitro when depolarized by potassium. In this study, we examined the release of IR-PRL from hypothalami obtained from intact and ovariectomized rats and incubated in the presence of veratridine (an alkaloid which depolarizes excitable membranes), angiotensin II, or thyrotropin-releasing hormone. Hypothalamic tissue spontaneously released IR-PRL, and this release was significantly increased by veratridine or angiotensin II in a dose-dependent manner. The specificity of the angiotensin-II-evoked IR-PRL release was demonstrated by the inhibitory effect of saralasin, an angiotensin II receptor antagonist, on hypothalamic IR-PRL release. Thyrotropin-releasing hormone (100 microM) had no effect on hypothalamic IR-PRL release. Ovariectomy decreased hypothalamic IR-PRL content and IR-PRL release in response to veratridine and angiotensin II. The effect of estradiol on hypothalamic IR-PRL content and release was also examined by obtaining hypothalami from ovariectomized rats injected with estradiol (1 microgram/day) or vehicle for 5 days. When compared with vehicle injected rats, administration of estradiol significantly increased the hypothalamic IR-PRL content (46 +/- 4 vs. 81 +/- 16 ng/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758582 TI - Modulation of the effects of N-methyl-D,L-aspartate on luteinizing hormone by the ovarian steroids in the adult rhesus monkey. AB - Although the excitatory amino acid, N-methyl-D,L-aspartate (NMA), is generally thought to stimulate LH release, we have previously reported that NMA inhibits LH secretion in the adult ovariectomized (OVX) rhesus monkey. The objectives of this study were: (1) to compare the effect of NMA on LH in the OVX monkey before and after replacement with ovarian steroids, and (2) to evaluate the LH response to NMA in the intact female monkey during three phases of the menstrual cycle. Three hourly injections of NMA (45 mg i.v.) were given to OVX monkeys (OVX; n = 12) and to OVX animals treated for 4 days with estradiol alone (OVX + E; n = 4) or with estradiol plus progesterone (OVX + E/P; n = 5). Replacement with ovarian steroids prevented the NMA-induced decrease in LH: mean (+/- SE) areas under the LH curve (expressed as a percentage of the 3-hour baseline preinjection control) during the 3-hour NMA treatment period were as follows: OVX, -26.6% +/- 2.4; OVX + E, +69.6% +/- 33.9; OVX + E/P, + 161.5% +/- 59.3 (p less than 0.001 vs. OVX). Three hourly NMA (45 mg i.v.) injections were also given to monkeys in the early to mid follicular phase (n = 5), the late follicular phase (n = 6) and the luteal phase (n = 11). NMA significantly increased LH in the luteal phase: control, 11.5 +/- 2.1; peak LH response, 19.8 +/- 2.1 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758583 TI - Sleep-related growth hormone secretion in human obesity: effect of dietary treatment. AB - Eight obese patients (4 male, 4 female; mean age = 35.9 years) before [mean body mass index (BMI) = 37.1] and after (mean BMI = 31.4) weight loss by means of a mixed hypocaloric diet were compared with 8 lean subjects (4 male, 4 female; mean age = 37.1 years, mean BMI = 22.3) in a study of their nocturnal sleep patterns and sleep-related growth hormone (GH) secretions. Although no sleep disorders (in particular, sleep apnea and hypersomnia) were observed, GH secretion was markedly altered in obese patients that showed no sleep-related GH peaks. After weight loss, the sleep architecture in obese subjects was unchanged. On the contrary, GH peak appeared to be only partially restored and delayed until after stage III-IV of non-REM sleep. Our study on obese subjects suggests that the altered nocturnal GH secretion, probably related to a hypothalamic dysfunction, may be the result of the obesity per se. PMID- 1758584 TI - Ultrastructural evidence of a sexual dimorphism in the neuropil of the medial preoptic nucleus of the rat: a quantitative study. AB - In the rat, a new structural sex difference of the nervous system was found: the density of axodendritic synapses (ADS) is larger in the male central component of the medial preoptic nucleus (MPNc), as proven by quantitative electron microscopy. The study included 24 animals divided into four groups (n = 6): control males (CM), control females (CF), males castrated as newborn (MGx) and males castrated as newborn and treated 10 days with daily injections of testosterone. No significant differences were found in the number of axospinous synapses among all groups; however, the number of ADS was significantly larger in CM when compared to that of the CF. This difference was abrogated by castration of the newborn male and restored by perinatal treatment with testosterone. Further, no difference in ADS was encountered between CF and MGx. The present data, together with previous studies which indicate that sex steroids do modify the number of synapses in other nuclei of the brain, led us to conclude that the sex difference in the number of ADS within the MPNc is determined by the organizational effect(s) of testosterone. PMID- 1758585 TI - Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty. AB - In both rats and primates, including humans, serum levels of insulin-like growth factor I (IGF-I) increase during the onset of puberty, suggesting a role for IGF I in this process. We examined the ability of IGF-I to affect the release of hypothalamic luteinizing hormone releasing hormone (LHRH) in prepubertal female rats. Our results indicate that IGF-I acts on the median eminence, which contains the highest density of type 1 IGF receptors in the brain, to elicit a dose related increase in LHRH release. In this regard, a minimal effective dose of 10 ng/ml (p less than 0.05) and a maximal effective dose of 100 ng/ml (p less than 0.01) was observed. IGF-II and insulin were one order of magnitude less effective. The results demonstrate that IGF-I has the capability to act directly upon the median eminence to effect release of LHRH, thereby suggesting a role for IGF-I in facilitating peripubertal changes in LHRH release. Thus, IGF-I may represent one of the 'metabolic signals' thought to be involved in the initiation of puberty. PMID- 1758586 TI - Antagonism of morphine-induced respiratory depression by novel anticholinesterase agents. AB - This study compared the effects of 3 novel antiAChE agents (derivatives of dimethylaminoethyl-phenyl carbamate) with that of physostigmine on the respiratory depression induced by morphine in rabbits. Each drug, RA6, (1 mg i.v., 2 mg s.c.) RA7 (1 or 2 mg i.v.); RA15 (0.25 or 0.5 mg i.v.), physostigmine (0.05 or 0.1 mg i.v.) or saline (1 ml), was injected simultaneously with morphine (8 mg i.v.) to groups of 6-10 rabbits. Respiration rate, blood gases and pH were monitored for 3 hr. Plasma ChE was measured before and at 15 min intervals after injection. The 4 antiAChE's were given to 40 other rabbits, which were sacrificed at the time of maximal antagonism of the respiratory depressant effect of morphine, in order to measure the activity of AChE in the medulla, cortex and hippocampus. Physostigmine (0.1 mg) only antagonized the increase in paCO2 induced by morphine at 15 and 30 min. The drugs RA15 (0.5 mg), RA6 (2.5 mg) and RA7 (2 mg) almost completely prevented the respiratory depression, without obvious signs of peripheral cholinergic hyperactivity, for at least 3 hr. There was no relationship between the degree of antagonism of the effects of morphine with any drug and that of inhibition of ChE in plasma. In contrast, a highly significant correlation (P less than 0.01) was found between the former and the amount of inhibition of AChE in the medulla. It is suggested that the novel carbamates may have potential therapeutic application in reducing the respiratory depression of opiates, without impairing analgesia. PMID- 1758587 TI - Effect of dietary protein on striatal dopamine formation following L-dopa administration: an in vivo study. AB - We varied the diet of rats and monitored extracellular levels of dopamine in the striatum. Following L-dopa administration, the increase in striatal dopamine levels was attenuated by 78% in rats that had consumed a high protein diet as opposed to a low protein diet. Similarly, the increase in striatal dopamine levels was attenuated by 61% in rats that had just eaten a protein-containing meal as compared to fasting animals. These findings demonstrate that dietary protein strongly affects brain dopamine formation from exogenous L-dopa. PMID- 1758588 TI - Hyperglycemia induced by hippocampal administration of neostigmine is suppressed by intrahypothalamic atropine. AB - We investigated the relationship between the hyperglycemia induced by the administration of neostigmine into the hippocampus and the hypothalamus. Prior to the injection of neostigmine (5 x 10(-8) mol) into the hippocampus, 1 microliter each of atropine or hexamethonium (5 x 10(-11)-5 x 10(-8) mol) was injected into the bilateral ventromedial hypothalamus (VMH). Atropine suppressed in a dose dependent manner the hyperglycemia induced by hippocampal administration of neostigmine, whereas hexamethonium had no significant effect. These observations suggest that the pathway for this experimental hyperglycemia involves, at least in part, the muscarinic cholinergic neurons in the VMH. PMID- 1758589 TI - Systemic morphine simultaneously decreases extracellular acetylcholine and increases dopamine in the nucleus accumbens of freely moving rats. AB - Microdialysis was used to measure extracellular levels of acetylcholine (ACh) and dopamine (DA) simultaneously in the nucleus accumbens (NAC) of freely moving rats. Systemic injection of morphine (20 mg/kg) significantly decreased ACh (30%, p less than .01) while it increased DA (55%, p less than .01). The effects of morphine were eliminated by naloxone. The results confirm that morphine increases DA and in addition, demonstrate an inhibitory influence of this opiate on extracellular levels of ACh in the NAC. PMID- 1758590 TI - The dorsolateral, suboccipital, transcondylar approach to the lower clivus and anterior portion of the craniocervical junction. AB - The authors review their experience with a dorsolateral approach to the anterior rim of the foramen magnum and adjacent region. The operative technique includes exposure of the vertebral artery at C1, partial resection of the occipital condyle and lateral atlantal mass, and extradural drilling of the jugular tubercle. This approach has been applied in six patients who harbored intradural space-occupying lesions located ventral to the lower brain stem. Excision of the neoplasm was virtually total in all but one patient, in whom biopsy was the primary goal of the intervention. No morbidity and no mortality were associated with this approach. The main advantage of the dorsolateral, suboccipital, transcondylar route is the direct view it offers to the anterior rim of the foramen magnum without requiring brain stem retraction. PMID- 1758591 TI - Cerebrospinal fluid shunting for hydrocephalus in the adult: factors related to shunt revision. AB - Cerebrospinal fluid shunting procedures are widely employed in the treatment of hydrocephalus and other disturbances of the dynamics of cerebrospinal fluid. In spite of its popularity, this operation frequently requires surgical revision. A retrospective analysis of a series of 356 adults who underwent the insertion of a cerebrospinal fluid shunt between January 1970 and December 1988 was performed. The incidence of revision was analyzed, and an attempt was made to identify possible causal factors. The overall incidence of surgical revisions was 28.65%; the number of revisions in the same patient ranged between one and eight. The most frequent causes of revision were distal malposition, obstruction, and infection. A statistically significant difference (P less than 0.05) was found in both the risk of revision in patients who had undergone previous operations and those who had not and in the incidence of revision before and after January 1985. Meticulous surgical technique as well as perioperative antibiotic prophylaxis appear responsible for the latter. The differences in the incidence of revision among patients treated with different types of shunts and valves, though remarkable, is not statistically significant. PMID- 1758592 TI - Pregnancy in patients with cerebrospinal fluid shunts: report of a series and review of the literature. AB - Hydrocephalic women with cerebrospinal fluid shunts are now surviving to reproductive age. Twenty-one pregnancies in 18 patients with shunts, including 11 from the present series and 10 from previous series, were analyzed for neurological, obstetrical, and perinatal outcome. Fourteen women had preexisting shunts, and 4 had the onset of symptomatic hydrocephalus and the placement of shunts during pregnancy. Neurological complications occurred in 13 of 17 (76%) pregnancies in patients with preexisting shunts, including symptoms of increased intracranial pressure (ICP) in 10 of 17 (59%) pregnancies, exacerbation of seizure disorder in 2 of 17 (12%) pregnancies, and severe headaches without increased ICD in 1 patient. In 7 of 11 (66%) of the symptomatic patients, symptoms spontaneously resolved postpartum. Four of 17 (23%) of these pregnancies were associated with shunt obstruction requiring antepartum or postpartum surgery. Four patients had a primary shunt placement, and one had a shunt revision during pregnancy without complications. There were no unusual obstetrical or perinatal complications in the series. The clinical management of pregnant patients with hydrocephalus should include preconception counseling and magnetic resonance imaging, as well as the use of serial antenatal magnetic resonance images, ICP monitoring, or the judicious use of radioisotope studies of shunt patency if signs of increased ICP appear. A cesarean section is recommended for the delivery of the neurologically unstable patient. For asymptomatic mothers, a vaginal delivery with a shortened second stage and prophylactic antibiotics are advised. PMID- 1758593 TI - A ventricular infusion technique for the evaluation of treated and untreated hydrocephalus. AB - Patients considered to have a possible disorder of the circulation of the cerebrospinal fluid (CSF) were prospectively randomized on clinical and computed tomographic grounds into one of four categories: low probability of a disorder of circulation of the CSF (n = 14); high probability of a disorder of the circulation of the CSF (n = 10); low probability of shunt malfunction (n = 10); and high probability of shunt malfunction (n = 9). Patients with possible disorders of the circulation of the CSF who did not meet the entry criteria for each of these categories were excluded from this study. A ventricular catheter connected to a subgaleal Rickham reservoir not in continuity with a shunt system (if this was present) either was inserted into each patient or was in place from previous surgery. Infusion studies were conducted by the infusion of 1 ml/min of normal saline through a 25-gauge needle inserted through the skin into the Rickham reservoir. A separate 25-gage needle was inserted into the Rickham reservoir for continuous recording of intracranial pressure. There were 43 infusion studies that were included in the four categories. Recordings of baseline intracranial pressure for a high probability of a disorder of the circulation of the CSF did not differ significantly from a low probability of a disorder of the circulation of the CSF. Baseline intracranial pressure for a high probability of shunt malfunction was significantly higher than the low probability of a disorder of the circulation of the CSF group and the low probability of shunt malfunction group; there was, however, marked overlap in values between these groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758594 TI - Anatomy of the sympathetic pathways in the carotid canal. AB - The sympathetic fibers in the carotid canal were studied in 30 unfixed specimens from human cadavers. Thirty petrous internal carotid arteries were injected with red silicone rubber, and the course of the sympathetic fibers was examined after removal of the inferior and superior wall of the carotid canal. The internal carotid artery was removed completely, leaving the sympathetic fibers intact as much as possible. Instead of a plexus-like configuration of the sympathetic fibers around the petrous carotid artery in all specimens, an anterosuperior group and a posteroinferior group of sympathetic fibers were found together, and both closed on the inferior-anterior side of the terminal portion of the horizontal part of the carotid canal. Seventy-three percent of the anterosuperior group of sympathetic fibers consisted of one large bundle, and 27% consisted of two smaller bundles. The majority of the posteroinferior group of sympathetic fibers consisted only of one bundle (93%). In 60% of the specimens, the majority of sympathetic fibers in the carotid canal were found in the anterosuperior group, 20% were found in the posteroinferior group, and in 20%, there was an equal distribution. The formation of the petrous bone and the related structures of the skull base play an important role in the configuration of these groups of sympathetic fibers. This study shows that, in cases of operative intervention in the carotid canal, the anterosuperior group of sympathetic fibers may be encountered. Damage to this bundle may result in sympathicoparesis, as it often contains the most sympathetic fibers. This group of sympathetic fibers can be easily separated from the internal carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758595 TI - The acoustic detection of intracranial aneurysms: a clinical study. AB - A new recording method for the acoustical detection of intracranial aneurysms is presented. A study examining the capability of the method to discriminate between patients with an aneurysm and control patients by a simple, objective parameter is reported. Sound signals were recorded over the eyes, and a real-time spectral analysis was performed on these signals. For this study, recordings performed on 26 patients with an aneurysm were compared with recordings on 26 age- and sex matched control patients without intracerebral abnormalities. As a result of measures taken to reduce artifacts and to improve the signal-to-noise ratio, the measurements were performed reliably, with little inconvenience for the patients; all measurements could be used for analysis. The power spectra measured in the control patients showed a typical, smoothly descending pattern; those measured in the aneurysm patients clearly differed from this pattern, showing peaks of varying width, height, and dominant frequency. For the objective judgment of the power spectra, the power median is introduced. The sensitivity and specificity of this parameter were determined. Possible methods to improve the results will be discussed. PMID- 1758596 TI - Inhibition of subintimal hyperplasia of autologous vein bypass grafts by nimodipine in rats: a placebo-controlled study. AB - An arterial bypass may be required for the management of neoplastic or cerebrovascular disease. When an arterial graft is not suitable, autologous vein grafts are the most commonly used conduits; however, as many as 20% of the vein grafts used in vascular surgery may occlude as a result of subintimal hyperplasia. Although the mechanism initiating subintimal hyperplasia remains unclear, it is known that subintimal hyperplasia is dependent upon smooth muscle cell proliferation and migration from the media to the intimal layer. The present study focused on the prevention of smooth muscle cell proliferation using a calcium antagonist. Forty rats received an autologous vein bypass graft from the jugular vein to reconstruct the abdominal aorta. They were randomly divided into two groups of 20 rats each. Animals in the treated group received a calcium antagonist (nimodipine), and those in the control group received a placebo. Nine months after grafting, the group receiving the calcium antagonist presented no or only slight sub intimal hyperplasia as compared with the placebo-treated group (P less than 0.001). These data suggest that a calcium antagonist could be used for the prevention of venous graft disease. PMID- 1758597 TI - Cerebral arteriovenous malformations: factors influencing the surgical difficulty and outcome. AB - The outcomes of 151 patients with arteriovenous malformations (AVMs) treated either surgically or conservatively are presented. In terms of long-term survival rate and follow-up results, the patients who underwent total excision had more favorable results than did those treated conservatively. Patient age was the most important clinical factors, with the preoperative level of consciousness being the second most important. A grading system was formulated on the basis of the angiographical factors by using multiregression analysis; the size of the AVM influenced the surgical outcome twice as much as did the location and the pattern of arterial feeding. Thus, a large AVM (greater than or equal to 4 cm) was given 2 points; a small AVM (less than 4 cm) was given 0 points; a deep AVM was given 1 point; a superficial AVM was given 0 points; an AVM supplied by three of more artery systems was given 1 point; and an AVM supplied by one or two artery systems was given 0 points. AVMs were categorized into 5 grades from Grade 0 to 4 by the summation of these points. Predicted Karnofsky scale after surgery was calculated by this grading system and the following equation: predicted Karnofsky scale = 87.2 - 5.6 x Grade. Grade 0 and 1 AVMs showed high rates of total excision (Grade 0, 94%; Grade 1, 82%) and of satisfactory outcome (Grade 0, 90%; Grade 1, 82%) and were classified as "easy" lesions. Grade 2 AVMs are lesions classified as "moderate" and had a total excision rate of 76% and a satisfactory outcome rate of 71%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758598 TI - Intracranial infection after missile injuries to the brain: report of 30 cases from the Lebanese conflict. AB - This study reviews the features of 30 intracranial infections complicating 600 penetrating head injuries from missiles in patients treated at the American University of Beirut Medical Center between 1981 and 1988. The follow-up period ranged from 1 month to 7 years (mean, 2.5 years). Sixteen patients had a brain abscess, 9 had cerebritis, 2 had an infected intracerebral hematoma, and 5 had meningitis. Infection developed 4 days to 7 years after the initial debridement. The infecting organisms were Gram positive in 11 patients (36%), Gram negative in 12 (40%), and a combination of Gram positive and Gram negative in 2 (7%). Twenty four patients (80%) had wound dehiscence or cerebrospinal fluid leakage at the time the infection appeared. There was a 76% correlation between the organisms cultured from the dehiscent scalp wound and the brain. Twenty-three patients had intracranial retention of bone. Infection developed in 16 of the 30 patients (70%) around bone fragments, in 4 around a metallic fragment, in 2 around absorbable gelatin sponge, and in 3 along the missile tract; 2 had an infected intracerebral hematoma, and 3 had meningitis. At least one of the following risk factors was present in each patient: extensive brain injury, coma, trajectory through an air sinus, cerebrospinal fluid fistula, inadequate initial debridement, or incomplete dural closure. The incidence of intracranial infection in patients with postoperative retention of bone was 4% in the absence of scalp wound dehiscence, compared with 84.6% when wound dehiscence was present. Ten patients (43%) still retained a bone fragment measuring less than 1 cm after excision of a brain abscess or treatment of cerebritis or meningitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758599 TI - The use of stable xenon-enhanced computed tomographic studies of cerebral blood flow to define changes in cerebral carbon dioxide vasoresponsivity caused by a severe head injury. AB - Previous studies using the xenon-133 cerebral blood flow (CBF) method have documented the impairment of CO2 vasoresponsivity after a severe head injury, but only global values can be obtained reliably with this technique. We studied CO2 vasoresponsivity using the stable xenon-enhanced computed tomographic CBF method, which provided information about well-defined cortical regions and deep brain structures not available with the xenon-133 method. In 17 patients with admission Glasgow Coma Scale scores of 8 or less, hemispheric CO2 vasoresponsivity ranged from 1.3 to 8.5% per mm Hg change in partial CO2 pressure. Lobar, cerebellar, basal ganglia, and brain stem CO2 vasoresponsivity frequently varied from the mean global value by more than 25%. In all but one patient, local CO2 vasoresponsivity in one or more of these areas differed from the mean global value by more than 50%. The greatest variability occurred in patients with acute subdural hematomas and diffuse (bihemispheric) injuries. This variability in CO2 vasoresponsivity has important implications for the effective and safe management of intracranial hypertension that frequently accompanies severe head injury. PMID- 1758600 TI - Effects of sympathectomy on skin and muscle microcirculation during dorsal column stimulation: animal studies. AB - Electric stimulation of the dorsal spinal cord (DCS) in the treatment of pain in peripheral vascular disease is known to enhance peripheral circulation, but the mechanisms are still obscure. An earlier study has provided indirect evidence that the vasodilator effect is dependent upon alteration of sympathetic vasomotor activity. In the present study, surgical interruption of sympathetic pathways was performed to define the role of the sympathetic system for the stimulation induced vasodilation. Three groups of normal rats were used: one group subjected to lumbar sympathectomy, one group sham-operated about 1 week before performing spinal cord stimulation, and a third group, without pretreatment, serving as a second control. Stimulation was applied to one dorsal column at the thoracolumbar junction, and peripheral microcirculation was recorded in hind limb skin and muscle by laser Doppler technique. The stimulation parameters were chosen to correspond with those used clinically in man. A cold test with monitoring of cold induced changes in peripheral blood flow was used to assess the completeness of the sympathectomy. The preoperative cold test induced a reciprocal response, vasoconstriction in the skin and vasodilation in muscle. DCS with clinical parameters did not produce this reciprocity in the control and sham-operated rats, but induced a vasodilation in both skin and muscle. After complete sympathectomy, defined as postoperative disappearance of the vasomotor responses to cold, the vasodilation in skin and muscle in response to DCS was abolished; however, the vasodilatory response to high-intensity stimulation (approximately 10 times the motor threshold) was not affected. Incomplete sympathetic denervation in some animals resulted in partial preservation of a vasodilatory response to DCS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758601 TI - Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. AB - Direct measurement of protein kinase C (PKC) activity in vitro revealed a significant increase in the activity of the enzyme in all human malignant glioma lines examined and the rat C6 tumor in comparison with control nonneoplastic astrocyte and mixed glial cultures. The total and particulate PKC activity in these cell types correlated strongly [r = 0.98 (P less than 0.001) and 0.94 (P = 0.002), respectively] with the maximal growth rates as measured by 3H-thymidine incorporation in each of the samples. An alteration in the growth rate of an individual glioma line (A172) by varying the serum concentration in the growth medium produced comparative changes in the measured PKC activity. The addition of the phorbol ester phorbol-12-myristate-13-acetate to this tumor line under high serum conditions produced down-regulation of the enzyme, which was accompanied by a corresponding reduction in thymidine incorporation. The administration of the PKC inhibitor staurosporine produced a dose-related decrease in the basal proliferation rate of glioma lines A172 and C6, as measured by 3H-thymidine uptake and confirmed by flow cytometry, indicating that the high intrinsic PKC activity is amenable to pharmacological manipulation. Cytofluorometric deoxyribonucleic acid cell cycle analysis of the tumors treated with PKC modulators demonstrated that reduced proliferation rates were caused by an inhibition of entrance into the deoxyribonucleic acid synthesis (S) phase (decrease in proliferative index), supporting the evidence that these modulators are not slowing the tumor growth in a nonspecific cytotoxic manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758602 TI - Blood-brain barrier permeability in an experimental model of bacterial cerebritis. AB - The mechanisms affecting blood-brain barrier (BBB) permeability in a brain abscess are not well defined. We sought to determine whether one bacterial species, Staphylococcus aureus, when inoculated into the brain, can cause the BBB to become abnormally permeable before leukocytes begin migrating into the brain. Cerebritis was induced by inoculating a suspension of S. aureus into the brain of the rat. The extent of leukocyte migration into the brain was assessed from histological sections at sequential times after the injection. BBB permeability was assessed by 1) detecting the presence of serum albumin leakage into the brain with a fluorescein-labeled antibody to rat albumin, and 2) detecting evidence of staining of the brain parenchyma with Evans blue dye. The fluorescein labelled anti-rat albumin antibody studies showed that the BBB was immediately damaged in experimental and control animals by the process of inoculation, but remained open to a greater extent in subjects inoculated with bacteria. Within 6 hours after inoculation, neutrophils began migrating into bacteria-inoculated brains. Evans blue dye, however, did not become detectable in the surrounding parenchyma until 72 hours later, long after leukocyte migration had occurred. The findings indicate that an acute disruption of the BBB in the needle track precedes leukocyte influx, but a more widespread increase in regional BBB permeability does not occur until 3 days after the bacterial inoculation. The time course for the development of increased vascular permeability suggests that a delayed product of the inoculation caused impairment of the regional BBB. PMID- 1758603 TI - Neurenteric cysts of the posterior fossa: recognition, management, and embryogenesis. AB - Neurenteric cysts are endothelium-lined structures most commonly encountered in the lower cervical or upper thoracic spinal cord. The occurrence of neurenteric cysts within the cranial vault is unusual. We present three patients with neurenteric cysts located within the posterior fossa: one near the jugular foramen deforming the 4th ventricle, a second in the cerebellopontine angle, and a third in the prepontine cistern. Several different theories have been advanced to explain the embryogenesis of neurenteric cysts. We review these theories and conclude that cranial neurenteric cysts may arise from a disturbance of early gastrulation, shortly after the onset of primitive streak regression. PMID- 1758604 TI - Neurological features of cranial vault lymphomas: report of two cases. AB - Two patients who had focal neurological deficits as the initial manifestation of a malignant non-Hodgkin's lymphoma involving the skull are described. Soft-tissue masses and variable bone destruction were the predominant computed tomographic findings, and magnetic resonance imaging studies revealed meningeal involvement in one case and sinus thrombosis in the other. Malignant non-Hodgkin's lymphomas initially appearing in the skull are rare, but these lesions should be considered in patients with a palpable scalp mass who have focal neurological signs. PMID- 1758605 TI - Plasmacytoma of the skull: case reports. AB - Two cases of solitary plasmacytoma of the skull are presented. Both patients underwent surgery, and the tumors were removed completely. The patients did not receive postoperative radiotherapy. After a follow-up period of 18 months, neither patients had a local recurrence, but one developed disseminated systemic myeloma. PMID- 1758606 TI - Cerebral metastasis from an epithelioid malignant schwannoma: case report. AB - The authors present a case of brain metastasis from an epithelioid malignant schwannoma. The patient previously had undergone a surgical resection of the primary tumor in the right forearm. The neoplasm was composed of nests of cells with an entirely epithelioid appearance without spindle cell areas. Immunohistochemically, the tumor cells stained positive for S100 protein and negative for cytokeratin, neuron-specific enolase, and anti-melanoma antiserum. To our knowledge, this is the first reported case of cerebral metastasis from an epithelioid malignant tumor of the peripheral nerve sheath. PMID- 1758607 TI - Cystic falcine chondroma: case report and review of the literature. AB - A rare case of falcine chondroma in a 25-year-old woman with an 8-year history of headache and a recent generalized seizure is presented. Microscopic examination of the resected tumor revealed that it was a falcine chondroma with chondrocytes and central cystic degeneration. PMID- 1758608 TI - Subintimal dissection of the vertebral artery in subluxation of the cervical spine. AB - The vertebral arteries appear to be particularly susceptible to injury in trauma of the cervical spine because of their close anatomical relationship to the spine; however, traumatic subintimal dissection of the vertebral artery is rare judging from the paucity of cases reported in the literature. The case of a patient who developed a visual field defect secondary to a fracture-subluxation of the cervical spine is reported. Angiography demonstrated an intimal dissection of the vertebral artery at the site of the fracture-subluxation resulting in thrombus formation and subsequently in emboli occluding the posterior temporal branch of the posterior cerebral artery. Early angiography is recommended if extracranial injury of the vertebral artery is suspected, and the institution of heparin therapy is necessary if a subintimal dissection is demonstrated. PMID- 1758609 TI - Hernia of the spinal cord: case report and review of the literature. AB - A rare case of a true hernia of the spinal cord through a dural defect without evidence of acute trauma is presented. The cause and the differentiation from other congenital and traumatic spinal cord lesions, especially arachnoid cysts, are discussed. PMID- 1758610 TI - Marked growth of a cerebral arteriovenous malformation: case report and review of the literature. AB - A case demonstrating the marked growth of an angiographically occult arteriovenous malformation is presented. A review of 58 cases in which an increase in the size of an arteriovenous malformation occurred suggested that the patient's initial age may have had an important role in such growth and that both the age and the duration of follow-up were related to the extent of growth. Follow-up neuroradiological examinations are thought to be necessary for patients who have had an episode of intracranial hemorrhage of unknown cause during childhood, even if the initial angiograms revealed no vascular lesion. PMID- 1758611 TI - A "PICA communicating artery" aneurysm: case report. AB - We present an unusual case of an aneurysm of the distal posterior inferior cerebellar artery (PICA). The aneurysm was associated with a unilateral PICA that supplied both cerebellar hemispheres and arose from an anastomotic vessel to the contralateral circulation, a branch of the contralateral PICA. Such an aneurysm has not been reported previously. The associated of vascular anomalies with aneurysms of the PICA is discussed. PMID- 1758612 TI - Extramedullary subdural meningioma after trauma. AB - A 61-year-old man had an extramedullary subdural meningioma occurring close to the site of an old vertebral traumatic fracture and spinal cord injury. The tumor was discovered 3 years after the spinal trauma. This finding supports the existence of a causal relationship between trauma and subsequent tumor development. A review of the literature disclosed only one other case of intraspinal meningioma after the traumatic fracture of the spine with spinal cord compression. PMID- 1758613 TI - Oscillopsia and primary cerebellar ectopia: case report and review of the literature. AB - Oscillopsia, the visual sensation of stationary objects swaying back and forth or vibrating, has been described in association with downbeat nystagmus in patients with primary cerebellar ectopia (Chiari I malformation). A patient with symptomatic oscillopsia without downbeat nystagmus, who was diagnosed by magnetic resonance imaging to have displaced cerebellar tonsils below the foramen magnum, is presented here. Suboccipital craniectomy and upper cervical laminectomy completely relieved the visual disturbance of the patient. The pathogenesis and surgical management of oscillopsia are discussed with respect to the current literature. Early recognition and surgical management of oscillopsia are lead to complete recovery in patients with minimal symptomatology. PMID- 1758614 TI - Posterior spinal osteosynthesis for cervical fracture/dislocation using a flexible multistrand cable system: technical note. AB - Cervical instability secondary to fracture/dislocation or traumatic subluxation involving the posterior elements may be treated by a variety of fusion techniques. The rigidity of the stainless steel wires used in posterior cervical fusions often leads to difficulty with insertion, adequate tension, and conformation of the graft construct. This report describes a technique of posterior cervical fusion employing a wire system using flexible stainless steel cables. The wire consists of a flexible, 49-strand, stainless steel cable connected on one end to a short, malleable, blunt leader with the opposite end connected to a small islet. The cable may be used in occipitocervical, atlantoaxial, facet-to-spinous process, and interspinous fusion techniques. The cable loop is secured by using a tension/crimper device that sets the desired tension in the cable. In addition to superior biomechanical strength, the flexibility of the cable allows greater ease of insertion and tension adjustment. In terms of direct operative instrumentation in posterior cervical arthrodesis, involving both the upper and lower cervical spine, the cable system appears to be a safe and efficient alternative to monofilament wires. PMID- 1758615 TI - Intrathecal morphine for postoperative analgesia in children after selective dorsal rhizotomy. PMID- 1758616 TI - Receptor binding of corticosterone in monoaminergic structures of the brain of rats after neonatal blockade of the hypophyseoadrenal system. PMID- 1758617 TI - Role of testosterone metabolism in the hypothalamus in the regulation of the gonadotropic function of the hypophysis in pre- and postpubertal male rats. PMID- 1758618 TI - Influence of biologically active substances of the spleen on the content of somatotropic hormone in the hypophysis of rats. PMID- 1758619 TI - Functional-statistical analysis of action potentials in the multineuronal activity of the brain of awake cats. PMID- 1758620 TI - Reaction of cats to species-specific acoustic signals during electrical stimulation of the hypothalamus before and after ablation of the sensorimotor region of the cortex. AB - The possibility of the formation under chronic experimental conditions of a reaction of a selective character to species-specific acoustic signals (SAS) of the agonistic type, presented to cats against the background of subthreshold electrical stimulation of hypothalamic divisions, was demonstrated. Reactions appropriate to the SAS presented appeared only in those animals in which threshold electrical stimulation evoked directed aggressive reactions. Partial bilateral ablation of the sensorimotor region of the cortex (SMC) did not influence the selective character of the reaction to the SAS, but led to a change by comparison with the preoperative period in the relationship of the motoric and acoustic reactions of the agonist type to conjoint acoustic and electrical stimulation. PMID- 1758621 TI - Dynamics of synchronization in the functioning of neurons of the new cortex and hippocampus during learning before and after the administration of nootropic agents and narcotics. AB - The principal difference in the effect of the preparations investigated resided in the fact that the nootropic agents did not change the effect of painful reinforcement on the synchronicity of neurons of the cerebral cortex of rabbits of the inhibitory type (coincidence of both the presence and absence of impulse activity), and of the activational type (the time of coincidence of only the presence of impulse activity). Both preparations mainly attenuated the initial influences of both the inhibitory and reinforced conditional stimuli on the synchronicity in the activity of the cortical neurons of both the activational and the inhibitory types. PMID- 1758622 TI - Neuronal correlates of the serotonin-dependent behavior of the pteropod mollusc Clione limacina. AB - A pharmacological model of hunting behavior, previously developed by the authors on the basis of the utilization of 5-hydroxytryptophan (5-HTP), a precursor of serotonin synthesis (5-HT), was employed in order to determine its cytochemical and neurophysiological correlates. In the presence of baseline behavior, 5-HT containing neurons were not detected by the glyoxylate method, but they were readily identified in the buccal, cerebral, and pedal (the greatest number) ganglia of the CNS and in the peripheral organs during hunting behavior induced by an injection of 5-HTP (100-200 micrograms/g). The disappearance of pauses in the initial unsustained fictive swimming, an increase in the frequency of the rhythm of swimming and in the generation of spikes in each cycle, as well as a change in the phasing of the locomotor cycle, the neurophysiological correlates of "fast" locomotion in the presence of 5-HTP-induced hunting behavior, were recorded in isolated pedal ganglia in the presence of 5-HTP (100-200 micrograms/ml). The activity of 5-HT-neurons of the pedal ganglia, which was initially synchronized with the episodes of swimming, increases against the background of 5-HTP and becomes continuous. The effects of exogenous and endogenous 5-HT on the generator of locomotion are identical, and are induced by the direct action of the mediator on the membrane of the locomotor neurons. The hypothesis of the participation of 5-HT in the monoaminergic control of behavior is discussed. PMID- 1758623 TI - Some neurophysiological mechanisms of the perception of interoceptive signals. AB - The principal objective of this study consisted in the identification of some basic mechanisms of the perception of the interoceptive signal. The EEG activation reaction through mechanoreceptive stimulation of the stomach served as the indicator. A positive relationship was found between the intensity of the activation reaction and the intensity of the stimulus employed; the extinguishability of the reaction in response to repeatedly acting interoceptive stimuli was also found. The characteristic features of the EEG activation reaction during an interoceptive effect and the characteristic on- and off responses (the development of the reaction at the beginning and ending of the action of the stimulus) were identified. The data presented are aimed at the disclosure of the interaction of the elements of the dual function of the interoceptive analyzer: as a feedback signal for the central apparatus subserving the control of visceral functions and as an important element of the nonspecific activation of the brain. PMID- 1758624 TI - Patterns of the functioning of the hypophyseoadrenocortical system in the presence of repeated stressful stimulations. AB - The relationship of the magnitude of the response of the hypophyseoadrenocortical system (HACS) to the strength of the stimulus in the presence of isolated or repeated stressor influences was determined in experiments on awake rats. Electrical stimulation of 0.1-0.9 mA of the skin of the paws for 3 min served as the stimulus. The reaction of HACS was judged on the basis of the determination of blood corticosteroids. Changes take place in the physiological characteristics of the system 30 mins after the termination of the stressor activation of the HACS. These changes do not depend on the strength of the initial stressor, and consist of a decrease in the threshold of excitability and a reduction in the maximum of the reaction to stressors of greater strength. The reaction to repeated stimulation at small strengths of the initial stressor proved to be larger or equal to the response of the system to the initial stimulation. At greater strengths of the stressor the reaction to repeated stimulation is significantly less than to the initial stimulation. PMID- 1758625 TI - Participation of beta-endorphin in the regulation of conditioned reflex activity of cats. AB - The role of beta-endorphin in the regulation of conditioned instrumental food procuring reactions and more complex forms of nervous activity such as reflexes of choice of the side of reinforcement was studied in cats. It was established that the subcutaneous injection of small doses of beta-endorphin (10 micrograms/kg, 15 x 10(-6) micrograms/kg) exerts a facilitatory nonspecialized effect on positive and negative food-procuring conditioned reflexes that has an overall adaptive character overall. The influence of the same doses of beta endorphin on conditioned reflexes of choice is more complex in character, depending upon the initial level of conditioned reflex activity and on the typological features of the experimental animals. A possible mechanism of the influence of beta-endorphin on higher nervous activity is discussed. PMID- 1758626 TI - Comparative assessment of the disorders of higher brain functions in various types of cerebral atrophy. PMID- 1758627 TI - Clinical heterogeneity of dementias of the Alzheimer's type. PMID- 1758628 TI - Clinico-genealogical study of Alzheimer's disease. PMID- 1758629 TI - Ultrastructure of the neuromuscular synapses of three types of muscle fibers of the rat diaphragm in acute chlorophos poisoning. PMID- 1758630 TI - Morphofunctional characterization of the neurosecretory cells of the supraoptic nucleus in rats with parathyroprival hypocalcemia. PMID- 1758631 TI - [Postoperative mortality and morbidity of patients in their late eighties]. AB - During the 12 year period, 1978-1989, 555 operations were performed at the Department of Clinica Chirurgica III of the University of Bologna, on 530 patients greater than 80 years old at the time of surgery. These were the indications for surgical procedure in these patients: malignant neoplasm of digestive system (243), other diseases of the digestive system (111), abdominal wall hernia (74), biliary disease (77), miscellaneous (50). The purpose of this paper is to define the role of surgery in patients over 80 years old. An acute complication required an emergency operation in 295 cases (53%). In all the other cases (260, 47%) an elective operation was performed. There were 63 deaths with an operative mortality rate of 11%. Among the patients who underwent elective surgery there were 11 deaths (4%); in the emergency group there were 52 deaths (17.6%). These rates were found to be statistically significant. The overall morbidity rate was 37.6% in the elective group and 49% in the emergency group. Also these rates were found to have a statistic significance. Then we have compared morbidity and operative mortality of over-eighty years old patients with the ones of two younger groups of patients: I group (age greater than 80 years), II group (age 65-80 years), III group (age less than 65 years). Patients of the three groups had undergone identical surgical operations for the same pathology. The operative mortality was 11% in the I group, 5.2% in the II group and 1.4% in the III group. The morbidity was 46%, 30% and 17% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758632 TI - [Lung surgery in patients over 70 years]. AB - The Authors according to their previous experience, report on the possibility of thoracic surgery in patients older than 70 with lung cancer. Fourty-seven patients older than 70 have been operated in the period 1984-1988 for lung cancer. The Authors performed 34 lobectomy, 11 pneumonectomy, and 4 wedge resection. The mortality rate was 4.25% (2 patients). Thirty-four patients are still living (follow-up range 12-60 months). Ten patients died. The Authors report a diagnostic and therapeutic guideline for this kind of pathology. PMID- 1758633 TI - [Reconstruction of the digestive tract after total gastrectomy. A comparison of Roux anastomosis with Nakayama's beta-anastomosis]. AB - Digestive tract reconstruction following total gastrectomy can be classified into two types according to whether the duodenal tract is excluded or preserved. Two groups of patients who underwent digestive tract reconstruction excluding the duodenal tract following total gastrectomy due to cancer were compared retrospectively: Nakayama's anastomosis was used in 20 patients (57%), and a Roux en-Y anastomosis was performed in 15 (43%). The main technical difference between the two groups consists in the distance between esophagojejunostomy and jejunojejuno anastomosis: 20 cm in the case of Nakayama's technique and 50 cm in the case of the Roux-en-Y reconstruction. Results showed that 40% of patients with Roux-en-Y anastomoses were asymptomatic compared to 60% of patients with Nakayama's beta-anastomosis (chi-square test, p = 0.36). The most frequent symptom in patients with Roux-en-Y reconstructions was a feeling of postprandial fullness (33%), whereas pyrosis (25%) was the most common compliant in patients with Nakayama's reconstruction. Endoscopy revealed the presence of esophagitis in 35% of patients with Nakayam's beta-anastomosis compared to 6.5% in patients with Roux-en-Y anastomosis (chi-square test, p = 0.012). Results confirm that a minimum distance of at least 50 cm between the esophagojejunal and jejunojejunal anastomoses is decisive in reducing the frequency of reflux esophagitis after total gastrectomy. PMID- 1758634 TI - [Circumscribed peritonitis of colonic origin]. AB - The Authors present their personal experience of circumscribed peritonitis of colic origin. They review some physiopathological aspects of these peritonitis and then emphasize the new therapeutic possibilities offered by percutaneous prick echo or TC guided. PMID- 1758635 TI - [Creation of a colostomy using a circular mechanical stapler]. AB - The paper describes the method used to create a preternatural anus in terminal stomas using a mechanical circular stapler (Model EEA-31). Two methods are put forward: Chung's and Burke's methods (the latter of which was used by our department). A mechanical circular stapler has been used several times (13) to perform this type of stoma, with excellent esthetic and functional results, both immediate and long-term. It was only necessary to reoperate in one case in order to suspend the affected colic loop. PMID- 1758636 TI - [The role of angiography in cryptogenic submesocolic digestive tract bleeding]. AB - Three cases of chronic gastrointestinal bleeding are described; the Authors emphasize the important role of mesenteric arteriography in establishing site and nature of bleeding. The review of international literature shows a success rate between 41 and 73% of cases studied with this method after negativity of other diagnostic procedures. PMID- 1758637 TI - [Observations on cancer metastasis from an unknown primary location]. AB - Following a short introduction in which the criteria used to classify patients suffering from cancer metastasis from an occult primary location are defined, the paper reports two cases of this type: an omental metastasis occluding the upper colon and an inguinal lymph node metastasis. Referring to the international literature, the Authors then analyse the reasons for the inability to recognise the neoplasm, its incidence, patients survival, the most appropriate diagnostic course and possible treatment of these cases. In conclusion, over and above the definition of a truly autonomous nosological status of metastasis of unknown origin, it is important to follow a correct diagnostic procedure in order to establish the most appropriate form of therapy. PMID- 1758638 TI - [Intestinal malrotations in the adult]. AB - The paper reports a case of intestinal malrotation in an adult patient with an anomalous location in the left hypochondrium of the cecum and vermiform appendix. The patient underwent explorative laparotomy for peritonitis due to acute appendicitis. Following a review of the literature, the anomaly was classified in embryological terms as a union defect during the third developmental stage of the umbilical loop. Attention is focused on the importance of an exact knowledge of the embryology of intestinal rotation in order to avoid technical surgical errors. In conclusion, the value of giving the patient precise iconographic documents is stressed in order to inform the surgeon who may have to operate on the patient's abdomen in the future. PMID- 1758639 TI - [Primary torsion of the omentum]. AB - The paper reports a case of spontaneous torsion of the omentum. Following a review of the international literature on the topic, the Authors discuss the pathogenesis, clinical symptoms and surgical therapy of this pathology. PMID- 1758640 TI - [Lesions of the duodenum from closed abdominal injury. A case report]. AB - Following a review of the literature, the paper reports a case of duodenal injury. This rare pathology most frequently affects the second half of the organ and may cause damage ranging from a simple hematoma to parietal laceration with peritonitis and/or retroperitonitis. Symptoms are often confusing and delayed, and together with chemical and instrumental tests do not always allow an early diagnosis to be made. Treatment varies according to the type of lesion and its location, and is often secondary to the general condition of the patient. Postoperative mortality appears to be limited to 11% if laparatomy is performed early (within 24 hours). PMID- 1758641 TI - [Efferent loop syndrome in gastric stump carcinoma. A clinical case]. AB - The Authors describe a case of efferent loop syndrome in a patient with inoperable gastric stump cancer. The resolution of the symptomatology by an anastomosis between afferent and efferent loop in a tract without neoplastic infiltration, permitted a six month good life period to the patient. PMID- 1758642 TI - [Parathyroid cysts]. AB - The Authors review the world literature on parathyroid cysts and report a case of this uncommon disease. The importance of an early pre-operative diagnosis by ultrasound, blood calcium level and parathyroid hormone assay with fine needle aspiration biopsy is pointed out. According to several surgeons, only the functioning parathyroid cysts require operation; needle aspiration may be appropriate therapy for the nonfunctioning ones. PMID- 1758643 TI - [Popliteal artery entrapment syndrome. Discussion of a case]. AB - The paper reports a case of popliteal artery entrapment syndrome (3rd type) associated with poststenotic aneurysm with a single painful ischemic attack. Diagnosis was made following an accurate anamnesis and clinical examination using invasive and non-invasive instruments. Surgical therapy consisted of resection of the gastrocnemius muscle followed by a graft to the self inverted saphena vein. PMID- 1758644 TI - Knowledge of HIV. PMID- 1758645 TI - Diltiazem and the elderly. PMID- 1758646 TI - Epidural trial in implantation of intrathecal morphine infusion pumps. AB - This retrospective review permits limited conclusions due to the small sample size and the limited control of variables. The temporary prepump, percutaneous epidural catheter trial is a useful component of our protocol. This period provides important information relative to possible side effects and efficacy of pain. The trial does give an estimation for the starting point of the intrathecal dosage but, as we have demonstrated, this is, at times, at a greater dosage than previously had been predicted. We feel that this retrospective review supports the continued use of a prepump trial of epidural morphine prior to permanent intrathecal pump implantation. PMID- 1758647 TI - Position paper: health access New Jersey. Medical Society of New Jersey. AB - The health care system in New Jersey is among the finest in the nation. This MSNJ position paper offers proposals to strengthen the system and to give the best care to all the citizens of New Jersey. The paper encourages a close relationship between government and physicians. PMID- 1758648 TI - Chronic steroid dependent asthma and pulmonary function. AB - The authors followed 84 asthma clinic patients, with an average age of 49 years, for 12 years. Pulmonary function studies consisting of forced expiratory volume in one second and forced vital capacity were performed upon initial evaluation and quarterly re-evaluation. PMID- 1758649 TI - Dentistry's role in treating sleep apnea and snoring. AB - Dental appliances have a place in the treatment of loud snoring and obstructive sleep apnea (OSA), and may be indicated for those patients who cannot tolerate continuous positive air pressure ventilation. Physicians and dentists must work together for the health, comfort, and well-being of patients. PMID- 1758650 TI - Urinalysis for the private office laboratory. AB - Urinalysis is the most frequently ordered test performed in the physician office laboratory. Quality control programs must be a part of every urinalysis ordered in the office laboratory. Quality control will assure the test will yield reliable information. PMID- 1758651 TI - Medical history: health care crusader, Florence C. Child. AB - In January 1924, Florence Chapman Child, MD, was elected to membership in the Mercer County Medical Society. Against great odds, she made her mark in medicine as one of the first women members of the County Society. Dr. Child will be remembered for her dedication to public health. PMID- 1758652 TI - Frustrated clinicians must seek out sources of support. PMID- 1758653 TI - New York State Coalition urges establishment of effective NP organization. PMID- 1758654 TI - Residencies are one option for apprehensive new practitioners. PMID- 1758655 TI - Development of an exercise program for older adults: pre-exercise testing, exercise prescription and program maintenance. AB - Health care practitioners have the technical skills, frequency of contact and credibility with older adults to use exercise as a health-promoting and disease preventing intervention. This article acquaints the clinician with how to develop an exercise program specifically for older adults. The health-promotion and disease-prevention outcomes of exercise in older adults, including an explanation of the three stages of exercise programming for older adults, are also reviewed. Stage one is labeled pre-exercise testing and discusses assessment protocols for aerobic capacity, body composition, flexibility and strength. Guidelines for who should and should not exercise are also explored. The second stage of exercise programming is exercise prescription. An explanation of how to develop a beginning level of training and guidelines for how to set goals based on the initial pre-exercise testing are presented. Program maintenance is the third stage; this includes suggestions for designing an exercise program that increases program compliance, reduces attrition and prevents relapses to non-exercise behaviors. PMID- 1758656 TI - Causes and treatment options for women with dyspareunia. AB - The incidence of dyspareunia, defined as difficult and painful intercourse, appears to be increasing. A symptom not a disease, dyspareunia is rarely reported by patients, even though it may be the actual reason why they seek health care. Often, patients will only discuss their concerns after questioning. Health care professionals who provide primary care to women must understand the various etiologies of dyspareunia. Possible causes of dyspareunia as well as current treatment modalities are identified. Sex education, counseling, vaginal dilatation and pelvic-relaxation exercises may be needed to restore the woman's confidence and decrease anxiety. Not until all organic causes of dyspareunia are ruled out, should the option of psychiatric intervention be suggested. PMID- 1758657 TI - Parallels between research and diagnosis: the reliability and validity issues of clinical practice. AB - There are many similarities between the methods used to conduct research and the strategies clinicians utilize to improve the quality of the data collected for diagnostic purposes. This article reviews basic reliability and validity issues as they relate to clinical practice. PMID- 1758658 TI - Screening for psychiatric morbidity in men and women. AB - This paper describes the use of the general health questionnaire (GHQ) to screen a random sample of men for psychiatric morbidity. The results are contrasted with those from the earlier Otago Women's Health Survey, an investigation into the sociodemographic determinants of psychiatric morbidity in Otago women. The level of psychiatric morbidity found in the men was equal to that found in the women which is in contrast to most overseas studies where men have been found to have lower levels of psychiatric morbidity to women. Significant differences were found in male and female demographic subgroups. High GHQ scores were found in separated, widowed and divorced men, men in higher socioeconomic status groups and those unemployed. High GHQ scores were found among the women aged 18-34, women who had never married, those in lower socioeconomic status groups and those unemployed. This study illustrates that gender needs to be considered alongside traditional sociodemographic factors when studying psychiatric morbidity and symptomatology. PMID- 1758659 TI - No evidence for social class inequalities in intervention for coronary heart disease in Otago 1987-9. AB - OBJECTS: to investigate whether social class differences in access to cardiac surgical interventions (angioplasties and coronary artery bypass grafting) could explain social class inequalities in mortality from coronary heart disease. METHODS: rates of therapeutic interventions to treat coronary heart disease were calculated for male patients aged less than 65 years admitted for the first time to Dunedin Hospital with a principal diagnosis of ischaemic heart disease (ICD codes 410-414) during the three year period from 1 January 1987 to 31 December 1989. Patients were categorised into different socioeconomic groups using the Elley-Irving social class scale. RESULTS: no statistically significant trend across social class was observed in the cumulative incidence of cardiac surgical interventions (angioplasties, coronary artery bypass grafts). Similarly there was no statistically significant trend across social class in the incidence rates of cardiac surgical interventions, even after adjustment for age. CONCLUSIONS: social class inequalities in access to cardiac surgical intervention do not appear to explain the observed inequalities in mortality from coronary heart disease. PMID- 1758660 TI - Regression of atherosclerosis: fact or fiction? PMID- 1758661 TI - Forensic psychiatry in New Zealand: a Canterbury perspective. PMID- 1758662 TI - Quadruple immunosuppression in renal allografts--the Auckland experience. AB - Recipients of live related and first cadaveric renal allografts were retrospectively reviewed before and after institution of a standardized regimen incorporating greater immunosuppression, (by the addition of antilymphocyte preparations). The two review groups were comparable with 11 live related and 27 first cadaver grafts in each. Despite a small advantage in terms of graft survival and diminished rejection, this was at the expense of septic morbidity. The implications of this are discussed. PMID- 1758663 TI - General practice--survival in the nineties. PMID- 1758664 TI - Opioids in the treatment of chronic pain of nonmalignant origin. PMID- 1758665 TI - Health reforms. PMID- 1758666 TI - Medical residency in the USA. PMID- 1758667 TI - Angina bullosa haemorrhagica: associated steroid inhaler use. PMID- 1758668 TI - Antibiotics for otitis media. PMID- 1758669 TI - Patients' addresses. PMID- 1758670 TI - Homoeopathy. PMID- 1758671 TI - AIDS. PMID- 1758672 TI - Whose quality of care is it, anyway? PMID- 1758673 TI - AMA sets policy on infectious disease and health-care workers. PMID- 1758674 TI - Renoir's maladies: the medical tribulations of an impressionist. PMID- 1758676 TI - Who do you influence? PMID- 1758675 TI - Ohio Cancer Information Service: a decade of experience. PMID- 1758677 TI - An accessory gluteus maximus muscle. PMID- 1758678 TI - Seasonal variations in the corpuscles of stannius in Notopterus notopterus (Pallas). AB - Seasonal changes in the corpuscles of stannius of Notopterus notopterus (Pallas) have been studied during various stages of reproductive cycle. During the pre spawning period, corpuscles of stannius are found as enlarged, oval or elongated in shape, lobes are clear and show cellular and nuclear hypertrophy while spawning phase shows atrophy in the corpuscles of stannius, their cells and nuclei. During post-spawning period corpuscles of stannius are more active than spawning phase and showed high physiological activity. Two corpuscles of stannius are also observed during this phase. This study shows that corpuscles of stannius are more active during late prespawning phase. During such period, animals are sexually mature and an increased estrogen secretion by the ovaries is naturally expected. This study suggests a correlation with the gonadal maturation and structural changes in the corpuscles of stannius during seasonal variations. PMID- 1758679 TI - A Golgi study on the neuronal organization of the habenular ganglion in the red stingray, Dasyatis akajei. AB - The neuronal organization of the habenular ganglion (HG) was studied in the red stingray using the rapid Golgi method. The HG was made up of the medial (MH) and lateral habenular nucleus (LH), and the former nucleus was further divided into a dorsal, intermediate and ventral subnucleus. Only one type of neurons were observed in the MH, while the LH was composed of two types of neurons. In the left HG cut at the rostrocaudal middle of the ganglion, the LH was located in the dorsolateral region, while the dorsal, intermediate and ventral subnuclei of the MH occupied the dorsomedial, intermediate and ventral portions of the ganglion, respectively. In contrast, the right ganglion seen at this level was composed exclusively of the MH, with the dorsal, intermediate and ventral subnuclei located in the dorsomedial, intermediate and ventral portions, respectively. In the caudal level of the left ganglion, each nucleus was seen almost in the same region as in the level of the rostrocaudal middle, however, three subnuclei of the MH fused with the same subnuclei of the opposite side. In the right ganglion at the caudal level, the LH appeared in the intermediate area. The right LH was far smaller and was located more ventrocaudally than the left LH. On account of the LH, the intermediate subnucleus of the MH was divided into a dorsal and ventral part. The dorsal and ventral subnuclei of the MH remained in the same region as in the rostral level. Thus, the HG of the red stingray exhibited a striking left-right asymmetry, the most remarkable aspect of which was considered to be differences of the size, form and location of the LH between the left and right HG. PMID- 1758680 TI - A Golgi study on the afferent fibers to the habenular ganglion in the red stingray, Dasyatis akajei. AB - Afferent fibers to the habenular ganglion (HG) were derived mainly from the stria medullaris thalami (SM), which was roughly divided into a dorsal and ventral bundle. In the left ganglion seen at the level of the rostrocaudal middle, the dorsal bundle gave off collaterals to the lateral habenular nucleus (LH) and dorsal subnucleus of the medial habenular nucleus (MH), while the ventral bundle innervated the intermediate and ventral subnuclei of the MH. On the other hand, in the right ganglion at the level of the rostrocaudal middle, the dorsal subnucleus of the MH was innervated by collaterals from the dorsal bundle of the SM, whereas in the intermediate and ventral subnucleus fibers from the ventral bundle were seen. In the left ganglion at the caudal level, the dorsal and ventral bundle extended medially and joined the same bundle of the opposite side to constitute a dorsal and intermediate component of the habenular commissure, respectively. A third component of the HC, a ventral component, was seen to run between the fasciculus retroflexus of both sides. As in the case of the rostral level, the dorsal bundle of the SM emitted collaterals to the LH and dorsal subnucleus of the MH, while the intermediate and ventral subnuclei of the MH were projected upon by collaterals from the ventral bundle of the SM. At the caudal level of the right ganglion, the dorsal bundle gave off collaterals to the dorsal subnucleus of the MH. In contrast, the LH and the intermediate and ventral subnuclei of the MH were innervated by fibers from the ventral bundle. With regard to terminal patterns of the SM, fibers to the MH gave off many short fine branchlets forming the glomerular structures, whereas those to the LH branched out into numerous terminals to form a dense fiber plexus. Thus, the afferent fibers to the HG in the red stingray exhibited a striking left-right asymmetry. PMID- 1758681 TI - Differential lectin binding on walls of thoraco-cervical blood vessels and lymphatics in rats. AB - Lectin binding in the walls of large to medium-sized blood vessels and lymphatics in the rat thoraco-cervical region was examined histochemically. The tunica intima of the aorta and superficial cervical artery showed positive reactions with wheat germ agglutinin (WGA) and Concanavalin A (ConA) but not with Dolichus biflorus agglutinin (DBA). The tunica media of the aorta exhibited intense WGA binding, especially on the smooth muscle cells, but the tunica media of the superficial cervical artery did not react with the lectin. Neither ConA nor DBA bound to the tunica media of the aorta and superficial cervical artery. The tunica adventitia of both arteries contained sites binding the three lectins, although DBA reactivity declined as the vascular diameter decreased. The tunica intima of the superior vena cava and azygos vein exhibited positive WGA and ConA binding, whereas DBA binding was noted on only part of the tunica intima of the superior vena cava and not on that of the azygos vein. The tunica media and tunica adventitia were reactive for all three lectins. The WGA and ConA binding sites in the tunica adventitia showed loose networks, suggesting lectin binding on connective tissue elements interlacing among smooth muscle bundles. Lectin binding sites in the walls of lymphatics exhibited an arrangement similar to those in the walls of the veins. Moreover valves protruding into the lumen showed intense WGA and ConA binding and scattered DBA binding. Three other lectins (Ulex europaeus agglutinin, peanut agglutinin, Maclura pomifera) were examined, but they showed no reactions with the vessels. Thus, the differential binding of lectins on the walls of blood vessels and lymphatics of various sizes suggests the functional complexity of monosaccharide residues in the vascular walls. PMID- 1758682 TI - Study on the subclavian artery and its branches in Japanese adults. AB - We examined the entire array of branches and the state of ramification of each branch of 144 subclavian arteries (Su) in 72 Japanese adults, and obtained the following findings. (1) The incidence of Type I -A(1) was 13.2%, the highest among the entire Su ramification. This was followed by Type I -B(1) at 9.0%, then Type I -A(2) at 6.9%, indicating considerable variation in the morphology of Su ramification. (2) Ontogenetic factors were implicated because of the existence of cases in which Su traversed the scalenus anterior muscle anteriorly (Type III: 0.7%), or was transfixed (0.7%). (3) Type 1-c was the form of thyrocervical trunk (Ttc) observed with the highest incidence of 31.3%. In addition, we propose that Types a-j (that were formed from a common trunk consisting only of the ascending cervical artery and inferior thyroid artery, and those in which another branch was included in this common trunk: 88.9%) be called Ttc. (4) The most common type of transverse cervical artery (Tc), which is formed from a common trunk consisting of superficial and deep branches, was found to be Type 1-a that branches from the first part of Ttc. It was observed with the highest incidence of 61.8%. Some of the superficial branches to the upper portion of the trapezius muscle that were independent and branched from Ttc (Types e, f: 2.8%), we called upper superficial branches. (5) The most frequently observed type of suprascapular artery (Ss) was Type b (38.2%), followed by Type a (25.7%), which branches independently from Su. We concluded that the sites at which Tc and Ss originate are the positions at which they traverse the brachial plexus (superior, transfixed to the plexus). (6) In cases in which the supreme intercostal artery (Is) and the deep cervical artery (Cp) were separate, (Types d-i excluding Type g: 31.9%), Is branched from a more proximal position than Cp. PMID- 1758683 TI - Microvascular architecture of the palatine mucosa in the common squirrel monkey (Saimiri sciureus). AB - Detailed observations were made of the structure and microvasculature of the palatine mucous membrane of the common squirrel monkey (Saimiri sciureus) by means of the plastic injection method under a scanning electron microscope. The findings obtained were compared with those of the Japanese monkey and other mammals. The osseous palate was flat horizontally and a pair of incisive foramina were apparently open at the anterior end of the hard palate. At the posterior end of the osseous palate, the pterygopalatine incisurae were found bilaterally. The incisive papilla was not obvious in form and size, and a pair of openings of the incisive canal were always situated on both sides of the papilla. The transverse palatine plicae or ridges numbered 7 or 8 symmetrically. They arched posterolaterally with an anterior protrusion near each median end. Posterior plicae were underdeveloped. Numerous openings of the palatine glands were found in the soft palatine mucosa. The arteries supplying the palate were the major palatine artery passing through the major palatine foramen and the soft palatine artery passing through the pterygopalatine incisura. The major palatine artery extended forwards giving off numerous medial and lateral branches, and its end on the respective side entered a small foramen located lateral to the incisive foramen. Medial and lateral branches formed the submucous arterial network. Arterioles diverging from this network were directed to the epithelial surface and formed an arterial network in the lamina propria. Further, capillaries diverging from the latter network built up the subepithelial capillary network immediately beneath the epithelium. Capillary loops sprouting from the capillary network were found in the form of a simple hair-pin without locational differences in their heights. The microvascular architecture thus displayed some similarity with that of the Japanese monkey. However, the vascular networks in the lamina propria and submucous layer were not distinct in size and scale as compared to those of the Japanese monkey. These differences may be related to the stature, living environment and food habits of this species. PMID- 1758684 TI - Tridimensional architecture of the lamina propria in the mouse soft palate, with special reference to the connective tissue papilla of the palatal papilla. AB - The NaOH cell-maceration method was applied to the oral surface of the mouse soft palate to demonstrate the tridimensional architecture of the connective tissue papillae (CTP) of the "palatal papillae", and of the openings of the glandular ducts. The CTP of the palatal papillae extremely differed from those of any types of the lingual papillae, and appeared as elliptical wall. Within the elliptical wall, there existed the semicircular or circular internal ridge which surrounded the round depression corresponding to the taste bud. The openings of the glandular ducts were rimmed by the collagen fibers running concentrically. Many fibrils derived from the concentrical fibers, turned to the sagittal direction and then concentrated into the sagittal fibers in the vicinity of the openings. PMID- 1758685 TI - Distribution of argininosuccinate synthetase-like immunoreactive neurons in the rat myenteric plexus: a whole mount study. AB - The distribution of argininosuccinate synthetase (ASS)-like immunoreactive neurons in the myenteric plexus of the rat alimentary tract were immunocytochemically studied using whole-mount tissues. The present study revealed ASS-like immunoreactive meshworks of ganglia and interconnecting nerve strands in the myenteric plexus of almost all parts of the alimentary tract. ASS like immunoreactive neurons constituted about 11% of the myenteric cell. PMID- 1758686 TI - On the facial artery of the raccoon dog (Nyctereutes procyonoides viverrinus Temminck). AB - Detailed observations were made of the facial artery in 20 raccoon dogs (Nyctereutes procyonoides viverrinus Temminck) utilizing the plastic injection method. The findings obtained were discussed in comparison with the facial artery of carnivorae. The facial artery diverged anterolaterally from the external carotid artery independently at a position between the origins of the lingual and the posterior auricular arteries when the external carotid bent laterally in front of the tympanic bulla. This artery, immediately after giving off the styloglossal branch, passed forwards superomedial to the digastricus muscle and medial to the insertion of the pterygoideus medialis muscle up to the posterolateral end of the mylohyoideus muscle, where the submental artery was derived. The submental ran forwards, giving off the digastric, the mylohyoid, the sublingual and the cutaneous branches, down to the posterolateral end of the intermandibular symphysis, where it anastomosed with the opposite fellow. The facial artery bent inferolaterally and passed laterally giving off the pterygoid and the inferior masseteric branches, and then emerged out onto the face through the facial vascular notch located inferoanterior to the angular process, which was extremely well developed in this species. The main stream of the artery ran anterosuperiorly at about 40 degrees to the horizontal plane along the anterior margin of the masseter muscle, since the notch was located on a projected level posterior to the middle of the zygomatic arch, giving rise en route to the anterior masseteric, the mandibular marginal, the buccal and the cutaneous branches. The artery finally divided into the inferior and superior labial arteries at the inferior margin of the mandibular origin of the buccalis muscle in the angle of the mouth. The facial artery of the raccoon dog was thus similar in its origin to that in the dog, cat and lion, but notably different in the short course of its submandibular region, and the nearly horizontal passage of the main route in the face, without the mandibular glandular branch. Additionally an extremely well developed angular process, a submandibular lobe and fairly posterior position of the vascular notch were found. PMID- 1758687 TI - On the laminar formation of the masseter muscle in the lion (Panthera leo). AB - An investigation was made of the laminar structure of the masseter muscle in 3 lions (Panthera leo s. Felis leo), and the findings obtained were evaluated in comparison with those in some other carnivora. Although the general aspect of the masseter of the lion resembled that of the cat, there was no close similarity or analogy between them. The construction of the masseter in the lion was as follows. The superficial layer consisted of primary and secondary sublayers, the intermediate layer was composed of anterior and posterior portions, and the deep layer also had anterior and posterior portions. Among these three layers (the masseter proper muscle), the superficial layer was extremely well developed as a characteristic feature of this species. The maxillomandibularis muscle was developed in a muscular element of its origin and had its tendinous insertion on the anteroinferior margin of the masseteric fossa. The zygomaticomandibularis muscle was also fairly well developed in the form of two muscular bundles which originated from the temporal crest, a shelf forming a lateral protrusion on the basis of the zygomatic process, and its posterior surface. Both muscles were also well developed as the masseter improper. Such a huge and complicated laminar pattern of the masseter muscle in the lion should be sufficient to exert a strong force as a predatory animal. PMID- 1758689 TI - [Experience with the management of pyogenic liver abscesses by percutaneous transhepatic puncture and drainage]. AB - The authors treated forty-two patients with liver abscesses guided by computer tomography or ultrasound percutaneous transhepatic puncture or drainage from January 1 1983, to 1989 December 31. Closed aspiration or drainage was done in 42 patients altogether 56 times. Three patients died (3/42 = 7.2%), postdrainage complications happened in 9 cases (9/42 = 21.4). Operative intervention was necessary in 11 patient after the percutaneous procedure (11/42 = 26.2%). The authors wrote about the technics particularly of the percutaneous puncture or drainage. The authors are considering the method as an effective treatment for pyogenic liver abscesses if the personal and technical circumstances are given. PMID- 1758690 TI - [Clavicle fracture in the newborn]. AB - The authors have found 244 clavicle fractures during 4131 vaginal delivery (5.91%). Both clavicles of three newborns have fractured. The incidence of fracture had relation to weight of newborns, to weakness of pains and to vacuum extraction. The Apgar score of the newborns with fractured clavicle was not less, than one of newborns with unbroken clavicle. None of 704 newborns from cesarean section, and none of 52 newborns, who was born out of the hospital had fracture of the clavicle. The cause of fracture is the violent hurry of delivery, the drawing of the head before birth of shoulders. One of 244 injured newborns had permanent brachial plexus palsy. Late complication was not found. Between the injured newborns was more frequent the jaundice requiring phototherapy. PMID- 1758688 TI - The origin and amplification of biomolecular chirality. PMID- 1758691 TI - [The effect of two different methods of jejunal feeding on pancreatic function]. AB - Pancreatic juice was continuously diverted from the Wirsungial duct by nasopancreatic drainage of the remnant of the gland after pylorus preserving partial pancreato-duodenectomy in 14 patients. On the 7th postoperative day with stabilized pancreatic secretion the juice was collected in 10 min fractions, while interdigestive secretory phases of the parenchyma were established by volume changes. At the beginning of a phase 100 ml slightly hyperosmolar (400 mosmol/L) oligopeptide diet with 90 kcal was given as a bolus injection for 7 patients or 60 min infusion into the second jejunal loop by fine needle catheter jejunostomy for 7 patients also. Pancreatic water, bicarbonate, protein, chymotrypsin, amylase levels peak, and integrated secretory responses were measured. It was observed, that infusion of the diet did not disturb cycling interdigestive phases and did not increase peak and integrated outputs. Bolus administration interrupted interdigestive phases and stimulated pancreatic water, bicarbonate, protein, chymotrypsin and amylase outputs nonparallelly. On the basis of their data authors concluded, that pancreatic secretion seems to be well preserved without duodenalregulatory mechanisms; and continuous jejunal infusion feeding seems to be useful in pancreatic disease and in other postoperative states when pancreas has to be put into rest. PMID- 1758692 TI - [CO2-laser surgery of rhinophyma]. AB - Authors are the first in Hungary to report on a CO2-laser dermabration performed for the treatment of rhinophyma. They describe the mode and results of the laser intervention justifying the application of the CO2-laser. PMID- 1758693 TI - [Sideroblastic anemias]. AB - The sideroblastic anaemias form a group of disorders of varying aetiology. They are being recognized with increasing frequency, especially as routine staining of bone marrow films for iron is now standard practice in most foreign laboratories. The sideroblastic anaemias have as a common feature the presence of large numbers of pathologic (ringed) sideroblasts in the bone marrow, ineffective erythropoiesis, a high degree of saturation of serum transferrin, increased levels of tissue iron and varying proportions of hypochromic erythrocytes in the peripheral blood. The marrow structure often exhibits dyserythropoietic features. Special attention has been focused by the authors upon the diagnostic and differential diagnostic problems, the ferrokinetics, the preleukemic condition and the therapeutics measures now available. There is also possible to draw some utilizable conclusions from the experiences of the authors. PMID- 1758694 TI - [Primary malignant pericardial mesothelioma]. AB - The case-history of a 41-year-old man is reported. He was admitted because of the sudden development of left hemiparesis, loss of consciousness and increasingly deeper coma. The ECG demonstrated second-degree AV block with Wenkebach conduction or episodes with complete AV block. The colour Doppler ultrasound and cranial CT examination revealed occlusion of the right internal carotid artery and a cerebral infarct of the right hemisphere. Within 24 hours patient died from herniation of the brainstem. Postmortem examination revealed a pericardial neoplasm infiltrating both left and right atrium, AV junctional area, interventricular septum and right ventricle. The tumor tissue grew transmurally and protruded into the cavities of the heart. The right internal carotid artery was occluded by a tumor embolism. The histochemical and immunohistochemical results proved that the tumor was a primary malignant pericardial mesothelioma. This kind of cardiac tumor involving the AV node and mimicking stroke is very rare. PMID- 1758695 TI - [Historical reflections on health protection and the condom]. PMID- 1758696 TI - [Principles and pathogenesis of post-traumatic axial malalignment in the growth years]. AB - Deviations of the axis or leg-length discrepancies after fractures in children and adolescents can be due to growth disturbances or can be the result of incomplete reduction of the fracture. We distinguish between four types of growth disturbances. In type I, the overall growth activity of the cartilage is increased; growth is then enhanced, which results in the affected bone being too long without deviation; this usually occurs after fractures of the metaphysis or diaphysis. In type II, activity, the epiphyseal cartilage is severely impaired or completely arrested. The direction of growth is unchanged. This results in shortening of the bone, usually due to severe damage to the germination zone of the growth cartilage after destruction of the vessels or infection. In type III, growth of the epiphyseal plate is partially stimulated. The consequence of this disturbance is deviation of the axis with overgrowth (this is in fractures of the proximal tibia). Type IV is characterized by an asymmetric arrest of growth. This results in deviation of the axis and shortening. The cause of such growth arrest can be epiphyseolysis or epiphyseal fracture. The defect in growth cartilage heals with a bone bridge. This is a very serious kind of growth disturbance, and it occurs in only 1% of all fractures before skeletal maturity. Correction after incomplete reduction of fractures during growth can be direct or indirect and specific or nonspecific. Direct corrections occur in combination with fracture healing; indirect corrections occur with physiological changes of the growing skeleton without association with the healing process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758697 TI - [Malunited supracondylar and condylar humeral fractures]. AB - We present three important types of posttraumatic deformity of the distal humerus: varus deformity, valgus deformity and complex deformity. Their primary causes are discussed. Slight varus deformities are the result of purely lateral slip of supracondylar fractures or radial overgrowth after a lateral condylar fracture. Severe varus deformities occur after ulnar slip of the distal fragment following supracondylar fracture caused by a rotational deformity. The results after correlation of varus deformities with a rotational deformity are poor. The only way of obviating this problem is to recognize a rotational deformity as soon as possible before adaptation of the elbow occurs, and also to correct it early, if necessary. Valgus deformities occur mostly after radial malunion. Depending on the size of the fragment and the disability of the patient, the fragment should be stabilized-but the potential involvement of the malunion in the elbow function must be borne in mind. Complex deformities and their unknown origins are also discussed. The correction of such deformities depends exclusively on the elbow function. More aggressive primary regimens are urgently needed to prevent the necessity for such secondary corrections, which are very demanding and, depending on the type, have a high failure rate. PMID- 1758698 TI - [The malunited juvenile fracture--Monteggia defect]. AB - Late reconstruction after neglected Monteggia lesions in children is discussed. On the basis of the literature (20 cases) and 2 personal cases it is deduced that open reduction of the radial head should be combined with osteotomy of the ulna according to the pathophysiology of the lesion. Details of the operative procedure are given. Reconstruction of the annular ligament is the least important part. Reconstruction is indicated in children under the age of 10-12 years even if the dislocation has been present for years. Unfavorable conditions for operative reconstruction are long-lasting dislocations in older children, deformation of the radial head, and imminent skeletal maturity. PMID- 1758699 TI - [Malunited juvenile fractures in pelvic and hip area]. AB - Fractures of the hip and pelvis are rare in the growing skeleton. Conversely, they are complicated by morphological and functional abnormalities in a particularly high percentage of cases. We present a review of posttraumatic structural abnormalities and their consequences. In addition to the common presentations, less well-known abnormalities and their possible treatments are discussed. PMID- 1758700 TI - [Malunited juvenile upper and lower leg fractures. Spontaneous correction, complications, indication for corrective intervention]. AB - If malunion occurs after shaft fractures of the femur or tibia, it often corrects itself spontaneously. If the remaining growth period is +/- 2 years, side to side dislocations, shortening and varus deformities (up to 15 degrees) are equalized. Valgus, recurvation and antecurvation equalize much more slowly and rotation deformities only at the femur. The indication to perform a corrective osteotomy before the end of growth is therefore rare, and the remaining axis deviations have a good long-term prognosis as far as arthritic changes are concerned. Exceptions of this rule are rotation deformities in the lower leg and progressive valgus after high tibial fractures. Contractures instabilities and overuse of neighbouring joints represent another indication for early correction osteotomies. Risk of damage to the growth plate limits the possibilities for performing corrective osteotomies in young children. On the other hand, stable fixation is of less importance. At the end of growth, the procedures are the same as for adults. PMID- 1758701 TI - [Malunited juvenile fractures in the knee joint region]. AB - There is a tendency for malunion to occur in fractures of the knee region in children because the growth plates are often affected. Leg length discrepancies are reported in more than 50% of the children and axis deviations in 20-40%. The prognostic significance of epiphyseal lesions is described (not always accurately) by the classifications of Salter and Harris or Aitken. Treatment is mostly directed at leg-length discrepancies and axis deviations by resection of callus formations, epiphysiodeses and osteotomies. A complete bone growth history is necessary to plan the operative procedure. PMID- 1758702 TI - [Malalignment following injuries of the distal tibia and epiphysis of the fibula]. AB - If the correct treatment is applied, growth disturbances following epiphyseal fractures of the distal tibia are rare. Even if the prognosis is good after the correct treatment of epiphyseal fractures of the distal tibia, the parents and child may have to be informed about growth disturbances. Most frequent is a varus deformity after asymmetric closure of the medial growth plate. If at least 2 years of growth can be expected, a callus resection according to Langenskjold is indicated. If this procedure fails, the ideal timing for a correction is the end of the growth. Imminent contractures can be an indication for early correction even if a recurrent deformity can be expected. An open-wedge osteotomy permits all three procedures to be carried out: callus resection, axis correction and leg length correction. If an incongruence of the joint is present, the closed wedge technique using an external fixator is indicated; correction of the leg length can be postponed. Joint incongruence reacts well to axis alignment. The pre arthrotic joint can remain free of symptoms for years. We never encountered epiphyseal fractures of the distal fibula, but we did see one case of deformity of the ankle joint as a result of closure of the proximal fibular growth plate. PMID- 1758703 TI - Perinatal events and further developmental outcome--assessment of a newborn's individual prognosis. 1. Neonatal period and results of an eight years' follow up. AB - The aim of the prospective study described in this paper was to develop a prognostic screening method which permits to give an individual prognostic estimate for every newborn, with an accuracy acceptable for clinical purposes. In the following, the condensed data of the case histories as well as of the clinical and laboratory findings in 47 of initially 60 preterm and term newborns with and without cardiorespiratory distress were analyzed under two different aspects. In the first part, the general statistical relationships are presented in the followed up children, who were classified under various groups according to the clinical course during the first two years of life and to the developmental stage reached at the age of two and six years. It was shown that such a procedure will not suffice in clinical practice for the purpose of individual prognostic estimates. The analysis of the clinical classifications of the six-year-old children in comparison with their school performance at the age of eight years yielded a high accuracy of the previous clinical estimation. PMID- 1758704 TI - Perinatal events and future developmental outcome--assessment of a newborn's individual prognosis. 2. Prediction of outcome on the basis of perinatological data--results of multivariate discriminant analysis. AB - The aim of the prospective study described in this paper was to elaborate a prognostic screening method which allows to give an individual prognostic estimate for every newborn, with an accuracy acceptable for clinical purposes. This second part informs about the results of multivariate discriminant analysis, using the data from case histories as well as from the clinical and laboratory findings in the neonates (including "criteria of hypoxia"). According to the kind and number of abnormalities found on the occasion of out-patient consultations during the course of the first two years of life, and according to the developmental status reached at the age of two and six years, the children were classified under two alternative groups. Satisfying results were achieved in the discrimination between the groups of six-year-old children. As compared with the literature, the prognostic method proposed in this paper yields a relatively high accuracy of individual predictions, and therefore promises to become a good tool for clinical practice. PMID- 1758705 TI - [Symptoms of tic in childhood]. AB - Literature at the tic phenomen of the last 100 years is reviewed. Phenomenology, incidence, etiology, differential diagnosis and therapy are exhibited. PMID- 1758706 TI - [The diagnosis of appendicitis in childhood]. AB - 89 preschool children, 2-4 years old, treated under the diagnosis of appendicitis were analyzed. 46 of them were operated. In 39% of those children the diagnosis of an acute nonperforated appendicitis could have been ensured, in 39% the diagnosis of a perforated appendicitis was found, in 22% the was found, in 22% the laparotomy was negative. In cases of an acute perforated appendicitis typical symptoms were vomiting (100%), general stomach-ache (89%) and fever (61%). In most cases of an perforated appendicitis the state of patients was reduced drastically (80%), in 50% an ileus could be observed. Half a children with an acute nonperforated appendicitis as well as an perforated appendicitis had got a respiratory disease additionally. This fact was the main reason for the to late diagnosis particularly in the age up to 3. In all cases being not sure a consequent control at a ward is necessary; an important fact for this recommendation is the shortness of the acute perforated appendicitis in early childhood. PMID- 1758707 TI - [Causes, mechanisms and therapy of functional fecal incontinence in children]. AB - 1. In case of encopresis in childhood about 50% are caused by disorders of perceiving the need to relieve the bowels and bowel movement, about 30% are caused by disorders of controlling the adaptation mechanism of the rectum or the defecation reflex and about 15% are caused by disorders of the sphincter apparatus. 2. A nonsurgical therapy must be a complex one. Its effect has to aim at concerning the psychoneurologic state, conalizing the reflexes, bettering the conductivity of the nerves as well as enhancing the sphincter-tonus. In addition to psychotherapy, gymnastics and sphincter-training the transrectal and intrarectal electrostimulation is of great importance. 3. To form an estimate of the mechanism of encopresis-pathogenesis many different methods are necessary and possible; these are the precondition for an effective differentiated therapy. PMID- 1758708 TI - Experimental approach to reflex sympathetic dystrophy and related syndromes. PMID- 1758709 TI - The epidemiology of pain in children and adolescents: a review. PMID- 1758710 TI - Adolescents use patient-controlled analgesia effectively for relief from prolonged oropharyngeal mucositis pain. AB - We compared patient-controlled analgesia (PCA) and continuous infusion (CI) morphine delivery in a randomized controlled trial in adolescents during oropharyngeal mucositis pain after bone marrow transplantation. Results from 20 patients who completed 7 or more days on study (10 PCA, 10 CI) were evaluated. The group means for age, weight and height were comparable. Daily measures were morphine intake, self-report of pain intensity and side effect scores. Over 10 study days, the mean cumulative morphine dose to subjects in each group was 4.94 mg/kg (PCA) vs. 12.17 mg/kg (CI); the difference is significant (P less than 0.01). No significant differences were found between the groups for patient ratings of pain intensity or side effect scores despite the large difference in mean morphine intake, but the PCA group tended to report less intense sedation and less difficulty concentrating. Adolescents can use PCA effectively and safely for 1-3 weeks. Morphine intake of adolescent patients using PCA morphine intake is significantly lower than that of similar patients receiving staff-controlled CI. PMID- 1758711 TI - Epidural opiates and local anesthetics for the management of cancer pain. AB - The role of epidural morphine in chronic cancer pain treatment is unresolved. In a population of 1205 cancer patients, the aggressive use of systemic opiates limited the trial of epidural analgesia to 16 cases. Successful analgesia was achieved with epidural morphine alone in 6 of these 16 cases following systemic opiate failure. The addition of bupivacaine produced analgesia in all of the 10 remaining cases and was successful chronically in 6 cases. Complications occurred in 11 of the 16 cases of epidural analgesia and included dislodged or broken catheters, pain on injection, hyperesthesia from epidural morphine and bleeding or infection related to the epidural catheter. Epidural morphine is indicated only in selected cancer pain patients and, although bupivacaine extends the efficacy of epidural analgesia, these methods are accompanied by problems and limitations. PMID- 1758712 TI - The role of injury discharge in the induction of neuropathic pain behavior in rats. AB - When sensory fibers are damaged, a discharge of impulses is emitted, which can last up to a few minutes. In the present study, we examined whether this injury discharge plays a role in triggering 'autotomy'--a behavior involving self-injury in animals that is induced by total denervation of a hind paw. Sensory input from the sciatic and saphenous neuroma is thought to elicit chronic pain sensations which cause the rat to injure the hind paw. In the present experiments: (1) injury discharge was prevented by using a local anesthetic block and (2) injury discharge was artificially prolonged by delivering 150 electrical pulses to the nerve just prior to transection, at a strength sufficient to drive A- and C fibers. In one group of animals, the nerve was stimulated at 0.5 Hz at which frequency a synchronous, repetitive activity in C-fibers augments the response of some nociceptive dorsal horn neurons by temporal summation ('wind-up'). In 2 other groups, the sciatic nerve was stimulated at 0.1 Hz and 10 Hz. The results show that blocking injury discharge significantly delayed the average time of onset of autotomy and suppressed it in magnitude compared to control rats. In contrast, electrical stimulation, especially at the 'wind-up' frequency, significantly shortened the onset of autotomy and enhanced its severity. Thus, in spite of its short duration, injury discharge affects the subsequent development of neuropathic pain related behavior. PMID- 1758714 TI - Improvement to the Hargreaves paw flick method. PMID- 1758713 TI - The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. AB - The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomic functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a 'strong but comfortable' intensity to 1 of 3 auricular points to be examined: (i) autonomic effects (autonomic point), (ii) pain threshold effects (wrist point), and (iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed. PMID- 1758715 TI - [Polymorphism, competition and evolution of spermatozoides]. PMID- 1758716 TI - [Bactericide activity of cefadroxil comparated with amoxicillin-clavulanic acid, cefaclor and josamycin]. AB - Betalactamase-producing organisms are responsible for an increasing number of ENT and lower respiratory tract infections. Or cephalosporins and the combination of amoxicillin with the beta-lactamase inhibitor clavulanic acid are alternatives to ampicillin therapy. The killing activity of cefadroxil on the organisms most often responsible for ENT and respiratory infections was evaluated in vitro using a viable bacteria count method, comparatively with cefaclor, josamycin, and amoxicillin-clavulanic acid. Killing activity was found to be time-dependent for all the antimicrobial agents studied. Cefadroxil exhibited the same bactericidal effect on Streptococcus pyogenes and S. pneumoniae than the other agents. Haemophilus influenzae and an increasing number of Pneumococcus strains were resistant to josamycin which is therefore not appropriate for first-line therapy. As compared with amoxicillin and amoxicillin-clavulanic acid, cefadroxil was less active on H. influenzae and more active on Staphylococcus aureus. Production of beta-lactamase failed to influence the killing activity of cefadroxil. These bacteriologic data, together with results of pharmacologic studies (long half life and good penetration within tissues) can explain the clinical successes obtained with cefadroxil in ENT and lower respiratory tract infections. PMID- 1758717 TI - [Polyurethane versus polyethylene: in vivo randomized study of infectious complications of central catheterization]. AB - Polyurethane (PU) and polyethylene (PE) catheters were distributed by randomization among adult ICU patients to evaluate the impact of the catheter polymer on the rate of catheter-related sepsis (CRS). The two catheters were otherwise strictly identical. Three hundred central venous catheters were randomized and inserted in the subclavian or internal jugular vein, at the discretion of the clinician. Mean duration of insertion was 9.2 (+/- 3) days for both catheter types and mean number of line openings was 159 (+/- 60). A bacteriologic culture using a variant of Maki's technique was performed on the 205 catheters removed before patient discharge. No significant differences were found between the two catheters. Total number of tip infections was 33 and polyurethane and polyethylene prevalence ratio was 0.7. A clinical evaluation was performed for the 183 catheters inserted for a least 48 hours (in 142 patients). Patients were divided into four clinical categories according to previously reported definitions (Brun-Buisson et al., 1987). Clinical tip-infection rate was 4.4% and polyurethane and polyethylene ratio was 0.7. For three additional catheters (1.6%), only the Luer-lock was infected. These three catheters were made of polyethylene and were inserted into the internal jugular vein. The Luer lock was made of polypropylene. PMID- 1758718 TI - [Cardiovascular responses to passive and active orthostatism in healthy subjects, in relation to age]. AB - Changes in heart rate induced by inclining an orthostatic table to 30 degrees and 60 degrees and by standing was studied in 200/healthy volunteers of either sex. Study subjects were divided in eight ten-year age groups, from 16 to 97 years. The 56-65 year age group was the youngest group to develop systolic orthostatic hypotension. This response occurred in 4% of subjects aged 56-65 years and became increasingly prevalent from one age group to the next (25%, 36% and 44%). In some patient, the fall in systolic BP reached 70 mmHg. Systolic hypotension occurred in some patients at 30 degrees but in most cases developed only at 60 degrees. No significant difference was found between the falls in SBP seen at 60 degrees and during active standing (90 degrees), indicating that muscular activity does not play a major role in BP regulation. Diastolic hypotension was less common and was mainly seen in patients above 75 (20%) who also had systolic hypotension. Orthostatism was responsible for tachycardia but this response became increasingly less common beyond 55 years of age (60, 60, 52 and 36% in the four age groups above 55). This reflects increasing loss of sensitivity of the baroreflex with advancing age. These date are useful for comparing the age specific effects of disease states (e.g. diabetes mellius, alcohol abuse) or treatments (psychoactive drugs, antihypertensive agents). PMID- 1758719 TI - [Role of Schistosoma mansoni bilharziasis in male hypogonadism]. AB - In tropical and subtropical areas, schistosomiasis may cause anatomic anomalies of the genital organs responsible for permanent or reversible infertility. Furthermore, it has been suggested that this parasitic infection may have adverse consequences on the endocrine system. To specify the effects of schistosomiasis on endocrine function, production of pituitary gonadotropins and testosterone in rats and hamsters experimentally infected with Schistosoma mansoni was studied. Prior to infection, hormone levels were within the normal range for our laboratory in all animals studied. Hormone levels (FSH, LH and testosterone) fell significantly in all experimentally infected animals, as compared with uninfected controls. These data suggest that the inhibitory effect (documented by the fall in all the hormone parameters studied) of Schistosoma mansoni on gonadal function is due to an action at the hypothalamic or pituitary level. The potential role of parasite ecdysteroids in the mechanism of action of schistosomes deserves to be studied. PMID- 1758720 TI - [Vaccination against hepatitis B virus at the Lyon Pasteur Institute. A seven year evaluation]. AB - Results of immunization against hepatitis B among Pasteur Institute staff members are reported. Prior to immunization, 439 subjects were tested for hepatitis B virus (HBV) markers, including HBs antigen, anti-HBs antibody, and anti-HBc antibody (Ausria, Ausab, Corab assays; Abbott). Forty-seven subjects tested positive for anti-HBs antibody. 317 subjects negative for all the HBs markers studied were given three intramuscular doses of Hevac B (Pasteur vaccins) at one month intervals. Anti-HBs antibodies were assayed after the third injection with the following results: mean titer, 1,454 mIU/ml, standard deviation, 5,349 mIU/ml, and range, 4 to 41,100 mIU/ml. Anti-HBs titers above 10 mIU/ml were found in 879.4% of subjects. Non-responders and weak responders (anti-HBs titer under 10 mIU/ml) were given a fourth dose of vaccine. Ultimately, after the last (third of fourth) injection 97.6% of subjects had protective antibody titers. No case of HBV infection was seen during the seven-year follow-up period. PMID- 1758721 TI - Histological evolution of peripheral T-cell lymphomas. Study of six cases. AB - The authors report 6 cases of histological transformation in peripheral T-cell lymphomas of low grade of malignancy. The transformation occurs in 75% of the cases, in extra-nodal sites and corresponds to a monomorphic of pleiomorphic large cell type. There is no discordance in the immunologic results between the two phases. The transformation seems to occur earlier than in B lymphomas, with a relative frequency of hematological manifestations and no therapeutic response. PMID- 1758722 TI - [Characteristics of the first penicillinase-producing strains of Neisseria gonorrhoeae isolated in Tunisia]. AB - The first penicillinase-producing strain of Neisseria gonorrhoeae was recently isolated in Tunisia (1989). Betalactamase production was detected by the iodometric agar test. Minimal inhibitory concentrations (MICs) in agar medium were 128 micrograms/ml for penicillin, ampicillin and amoxycillin. With the amoxycillin-clavulanic acid combination, MIC fell to 0.25 microgram/ml. An Asian type plasmid pattern was evidenced in this strain, with presence of the 2.6 Mdal cryptic plasmid and of a 4.5 Mdal plasmid. PMID- 1758723 TI - [Vancomycin in 1991: current status and perspectives]. AB - Vancomycin is a narrow-spectrum glycopeptide antibiotic which is primarily active against Gram-positive organisms. Bacterial resistance develops rarely due to its numerous modes of action. The mode of action of vancomycin involves the inhibition of peptidoglycan synthesis. Vancomycin forms a stoichiometric complex with the peptidoglycan precursor UDP-N-acetylmuramyl pentapeptide by forming hydrogen bonds. In patients with renal insufficiency vancomycin clearance is reduced and elimination half-life prolonged. Vancomycin is the drug of choice in the treatment of methicillin-resistant staphylococcal infections and in the treatment of Gram-positive endocarditis and has been used as alternative therapy in the treatment or prophylaxis of Gram-positive infections in penicillin allergic patients. PMID- 1758724 TI - [Antiphospholipid antibodies--antiphospholipid syndrome. Cause or consequence of thrombosis]. AB - Antiphospholipid antibodies (APA) are heterogeneous immunoglobulines of G, M or A classes with specificity directed towards anionic phospholipids. The APA are associated with a wide variety of diseases. They have been found to represent risk factor for development of arterial and/or veinous thrombosis. The APA would perturbed the biological activities of anionic phospholipid surface in a manner that could decrease the natural anti-coagulant pathway in order to lead to thrombosis. In the latter hypothesis APA would appear as a secondary response to the exposure of phospholipid "self antigens" by activated or damaged blood vascular cells by known stimuli able to induce thrombosis. In these cases APA would therefore constitute a marker of risk of thrombosis. The question which remains to be solved is if APA possess their own pathogenic potential or if they appear as the result of an up-stream pathological event known to be favourable to the development of thrombosis or if both mechanism are involved. PMID- 1758725 TI - [Lipid peroxidation]. AB - After a brief review of the concepts of free radical and enzymatic lipid peroxidation, spontaneous peroxidation (initiation, propagation, termination, end products) is described in detail on the basis of the latest published studies shedding new light on the role of this process in a wide variety of disease states. Toxic effects of lipid peroxidation and physiologic protective mechanisms are described. Currently available routine methods for evaluating lipid peroxidation, particularly in plasma, although imperfect, are nevertheless valuable in clinical practice in view of the many human disease states involving lipid peroxidation. PMID- 1758726 TI - Effect of positive end-expiratory pressure on respiratory compliance in children with acute respiratory failure. AB - We studied the effect of positive end-expiratory pressure (PEEP) on the compliance of the respiratory system (Crs) in 25 children (age, 3 weeks to 10 years) requiring mechanical ventilation. Functional residual capacity (FRC) measurements were performed at 2 cm H2O increments, from 0 to 18 cm H2O of PEEP, and the FRC values were regressed versus PEEP. Static Crs, Crs/kg, and specific compliance (Crs/FRC) were calculated for each PEEP level. When FRC normality was reached Crs/kg improved in 15/25 (60%) patients but decreased in 2/25 (8%). Overall, Crs/kg increased from a mean +/- SE of 0.94 +/- 0.09 to 1.35 +/- 0.13 mL/cm H2O/kg (P = 0.003) and Crs/FRC from a mean +/- SE of 0.067 +/- 0.006 to 0.077 +/- 0.007 mL/cm H2O/mL (P = 0.057). The maximum compliance (mean Max Crs/kg, 1.56 +/- 0.12 mL/cm H2O/kg, and mean Max Crs/FRC, 0.089 +/- 0.005 mL/cm H2O/mL) was significantly higher than the compliance at the clinically chosen PEEP level and the compliance at the PEEP that normalized FRC. Maximum compliance was achieved within 4 cm H2O of the PEEP that normalized FRC. In 14/25 (60%) of cases the PEEP at maximum compliance coincided with the PEEP that resulted in FRC normalization. We concluded that static respiratory compliance improves in most (but not all) children with acute respiratory failure when FRC is normalized. Static respiratory compliance reaches maximum levels at PEEP values that are close (but not equal) to those that result in FRC normalization. Thus, assessment of the effect of PEEP on compliance is required in individual patients. PMID- 1758727 TI - Pulmonary mechanics and outcome of neonates on ECMO. AB - Deciding when to wean neonates from extracorporal membrane oxygenation (ECMO) can be difficult. The usefulness of simple measurements of pulmonary mechanics e.g., dynamic compliance (Cdyn) has been questioned. We investigated the pulmonary mechanics of eight neonates using the interrupter technique, which allows the partitioning of pulmonary mechanics into compartments representing the conducting airways and more peripheral phenomena (viscoelastic properties and "pendelluft"). Three neonates required ECMO for a congenital diaphragmatic hernia (CDH), two for hyaline membrane disease (HMO), two for meconium aspiration syndrome (MAS), and one for pneumonia. All neonates with MAS, HMD, and pneumonia were successfully weaned from ECMO when their Cdyn was 0.3 mL/cmH2O/kg or greater [mean 0.34 +/- 0.06 (SEM)]. All three neonates with CDH died and their highest Cdyn was 0.21, 0.19, and 0.09 mL/cmH2O/kg respectively (mean, 0.16 +/- 0.037). The airway resistance (Raw) and the slower component of pressure change after interruption (delta Pdiff), a measure of the more peripheral phenomena of the lung, were not significantly different in those neonates who survived and those who did not. The values for delta Pdiff in all patients were higher than those in healthy neonates. However, the Raw was not different. This suggests that the major disturbance in pulmonary mechanics was distal to the conducting airways. Those neonates who were successfully weaned from ECMO had a significantly higher Cdyn 24-48 hours prior to decannulation. Considering the lung as a two-compartment model offers no advantages when compared to the one-compartment model for the prediction of the outcome of a neonate on ECMO. PMID- 1758728 TI - Respiratory responses of piglets to hypercapnia during postnatal development: effects of opioids. AB - Resting respiratory and cardiovascular functions and the response to CO2 rebreathing were compared between 2.5 +/- 0.7 (mean +/- SE) and 34.1 +/- 1.9 day old piglets, before and after the opioid antagonist naltrexone (1 mg/kg IV). At rest, tidal volume, both absolute and per m2, inspiratory and expiratory time, absolute minute ventilation, and mean arterial pressure increased with age, and breathing frequency, minute ventilation per m2, and heart rate decreased, all of these with as well as without naltrexone. During hypercapnia, the pattern, but not the quantitative aspects of breathing changed with age. At rest, naltrexone produced hyperventilation in the young, but not in the older group. During hypercapnia, naltrexone had a sparse effect in both ages. We conclude that, in the anesthetized piglet, ventilatory functions at rest undergo change with postnatal age, but breathing responses to hypercapnia exhibit maturation in pattern only and not in magnitude. Whereas resting ventilation of young piglets is modulated by endogenous opioids, hypercapnia may activate opioids to a limited extent and in a manner unrelated to age. PMID- 1758729 TI - Efficacy, results, and complications of mechanical ventilation in children with status asthmaticus. AB - We have conducted a retrospective survey of 79 children out of a total hospital asthmatic patient population of 2,412, admitted over a 32 month period to the ICU for the management of severe status asthmaticus. All patients were in severe respiratory distress with CO2 retention; 19 required mechanical ventilation due to increasing fatigue and worsening bronchospasm, having failed to respond to either inhaled or IV bronchodilator therapy. All patients were ventilated at slow rates (less than 12 min) and their airway pressure (Paw) was deliberately kept below 45 cmH2O, while accepting a PaCO2 in the 45-60 mmHg range, as long as the pH was compensated. Although two patients developed pneumothoraces while on positive pressure ventilation, these were resolved without incidents. Five patients who had mediastinal or subcutaneous air leaks prior to intubation did not develop pneumothoraces. Following the initiation of mechanical ventilation, IV beta-agonist therapy was increased in order to reverse the bronchospasm and reduce the duration of mechanical ventilation. Mean duration of intubation was 42 hours. Fourteen of the 19 patients were weaned and extubated within 48 hours. All patients survived without sequelae. We conclude that a degree of controlled "hypoventilation" by deliberately choosing Paw less than 45 cmH2O can be successfully used to ventilate children with severe status asthmaticus with a reduced rate of pressure-related complications. PMID- 1758730 TI - Asthma in the vicinity of power stations: I. A prevalence study. AB - Respiratory symptoms, atopy, and bronchial reactivity were measured in primary school children living in Lake Munmorah (LM), a coastal town near two power stations, and in Nelson Bay (NB), a coastal town free from any possible major sources of outdoor air pollution. A prevalence survey and longitudinal follow-up study were performed 1 year apart. In both studies, the prevalence of ever wheezed, current wheezing, breathlessness, wheezing with exercise, diagnosed asthma, and use of drugs for asthma at LM were all approximately double the prevalence at NB (all P values less than 0.01). The prevalence of bronchial reactivity was significantly greater at LM than NB (P less than 0.01) at the first but not the second survey. By contrast, no significant differences were found between the two areas for skin test atopy or for parental history of allergic disease. Multivariate analysis supported the conclusion from the univariate analysis that there was more wheezing at LM compared to NB at both studies, when adjusted for atopy, smoking in the home, age, and sex. As expected, a positive skin test reaction to house dust mite was the predominant explanatory variable. Asthma was more common in the community near power stations (LM) than in the NB area. The absence of significant differences in skin test atopy and parental history of allergic disease argued against major genetic differences between the two groups. By contrast, the more common reporting of siblings' chest disease and asthma in Lake Munmorah supported an environmental cause. PMID- 1758731 TI - Asthma in the vicinity of power stations: II. Outdoor air quality and symptoms. AB - To assess longitudinally the effect of living in the vicinity of coal-fired power stations on children with asthma, 99 schoolchildren with a history of wheezing in the previous 12 months were studied for 1 year, using daily diaries and measurements of air quality. The children had been identified in a cross sectional survey of two coastal areas: Lake Munmorah (LM), within 5 km of two power stations, and Nelson Bay (NB), free from major industry. Daily air quality [sulphur dioxide (SO2) and nitrogen oxides (NOx)], respiratory symptoms, and treatment for asthma were recorded throughout the year. Measurements of SO2 and NOx at LM were well within recommended guidelines although they were several times higher than at NB: maximum daily levels in SO2 (micrograms/m3) were 26 at LM, 11 at NB (standard, 365); yearly average SO2 was 2 at LM, 0.3 at NB (standard, 60); yearly average NOx (micrograms/m3) was 2 at LM, 0.4 at NB (standard, 94). Marked weekly fluctuations occurred in the prevalence of cough, wheezing, and breathlessness, without any substantial differences between LM and NB. Overall, the prevalence of symptoms was low (10% for wheezing, 20% for any symptom). Whether the daily SO2 and NOx levels affected the occurrence of respiratory symptoms was investigated in children at LM using a logistic regression (Korn and Whittemore technique). For these children as a group, air quality measurements were not associated with the occurrence of symptoms. PMID- 1758732 TI - Effect of airway inertance on linear regression estimates of resistance and compliance in mechanically ventilated infants: a computer model study. AB - Respiratory inertance (I) is usually ignored when resistance (R) and compliance (C) of mechanically ventilated infants are estimated by least squares linear regression. Values of I that have been reported for these patients can cause impedances whose magnitudes approximate respiratory resistance. We show theoretically that if inertance is neglected no error is expected in resistance estimates, but a positive bias in compliance can be, proportional to the inertance, the compliance, and the sinusoidal frequency at which the measurements are made. To determine the errors in parameter estimates when the pressure waveform is non-sinusoidal, we simulated linear regression based on non-inertive and inertive models. R, C, and I of the simulated lung were varied over the range expected in an infant intensive care unit. The ventilator was simulated as a critically damped second order system with a square pulse input. The rise time (TR) of the pressure pulse was varied over the range reported in infant ICUs. Simulated measurements confirmed that resistance is correctly estimated if inertance is neglected. Maximum error in compliance estimates (13%) occurred when TR and R were low, and C and I were high. The variation in the error in estimated compliance was consistent with the theory. Coefficients of variation of the parameters, the standard errors, and R2 of the regressions tended to deteriorate with increasing compliance error, but the relationships were not single valued. These statistics may alert investigators to possible bias in compliance caused by neglected inertance, but cannot be used to correct any bias. PMID- 1758733 TI - Regional cycles of perfusion and non-perfusion in the lung of the term fetal rabbit. AB - The spatial distribution of pulmonary blood flow and its change over time was investigated in term fetal rabbits, using the plasma tracer fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). A tracer bolus was injected intravenously and allowed to circulate in vivo for increasing periods of time (2-30 minutes) prior to arrest of the circulation and tissue preparation. Initially, fluorescence was present in the vasculature of 43% of lung parenchymal tissue, disposed as discrete regions or "lobules." Interspersed regions of lung tissue received no tracer inflow. With increasing tracer circulation times (10, 20, and 30 minutes), a greater percentage of lung cross-sectional area contained vessels exhibiting tracer fluorescence (64, 96, and 100%, respectively). In the fetal lung, a high pulmonary vascular resistance (PVR) is maintained. Our studies indicate that, at any given moment, fetal pulmonary blood flow is distributed only to a proportion of discrete lung "lobules," while interspersed "lobules" receive no flow at all. The "lobules" alternate between these "high" and "low" vascular resistance states with a periodicity of approximately 35 minutes, comprising 22 minutes of non-perfusion followed by 13 minutes of perfusion. This circulatory pattern permits both the maintenance of high PVR and uniform lung development. Further, by directing flow to only a portion of the vasculature, greater microvascular flow rates are achieved and hence the risk of blood sludging and stasis is reduced. Recruitment of these "non-perfused" regions at birth could thus produce a significant reduction in PVR. PMID- 1758734 TI - Effects of a clinically detectable PDA on pulmonary mechanics measures in VLBW infants with RDS. AB - We examined the effect of a clinically detectable patent ductus arteriosus (PDA) and its successful treatment with indomethacin on serial measures of pulmonary mechanics in 10 very-low-birthweight (VLBW) intubated infants with respiratory distress syndrome (RDS). Pulmonary mechanics were measured by the passive expiratory flow technique. Total respiratory system compliance (Crs) gradually improved as RDS resolved. However, a significant decrease in mean Crs was associated with the development of a clinically detectable PDA, ranging from 1.51 +/- 0.21 to 0.90 +/- 0.08 mL/cmH2O/m (P less than 0.05). We also noted an increase in mean Crs, from 0.90 +/- 0.08 to 1.49 +/- 0.21 mL/cmH2O/m (P less than 0.05), after successful treatment of a PDA with indomethacin. Total respiratory system resistance (Rrs) did not change. We conclude that a clinically significant PDA is associated with a decreased Crs and that successful treatment of a PDA with indomethacin is associated with an improvement in lung compliance. These findings imply that the development of a clinically detectable PDA and its subsequent treatment complicates the interpretation of pulmonary mechanics data in VLBW infants with RDS. PMID- 1758735 TI - The use of peak expiratory flow rate measurements in respiratory disease. PMID- 1758736 TI - Retrosternal density: pulmonary underdevelopment or accessory hemidiaphragm. AB - Vertical retrosternal density paralleling the sternum, with haziness of a hemithorax on chest roentgenogram, often challenges the clinical acumen of pediatricians, chest physicians, and pediatric radiologists alike. Its presence has been historically linked to either pulmonary underdevelopment and/or accessory hemidiaphragm. The surgical and radiological pediatric literature has long debated this topic, but unfortunately, it has not received much attention in the general pediatric or in pediatric pulmonology literature. The similar radiologic appearance of these two entities can cause confusion both in diagnostic and the therapeutic approach. Many authors advocate an invasive modality, including thoracotomy, as the only definitive way to differentiate between them. We present two similar cases with retrosternal densities, review the pertinent literature, and propose a rational approach to diagnosis and treatment. PMID- 1758737 TI - Occurrence of respiratory syncytial virus subtypes in hospitalized children in Cleveland, Ohio from 1985 to 1988. AB - In order to determine the frequency of occurrence of the two respiratory syncytial virus (RSV) subtypes in hospitalized children in Cleveland, Ohio, we analyzed clinical isolates obtained during three consecutive winter epidemic seasons between 1985 and 1988. RSV was recovered from the frozen clinical specimens of 197 patients: 176 subtype A, and 21 subtype B. Subtype A predominated during all three epidemic seasons, ranging from 83 to 94% of isolates. We surveyed the clinical records of 16 children with subtype B, and 101 children with subtype A infections, hospitalized at the University Hospitals of Cleveland during these winter epidemics and found no differences in age, sex, race, or clinical spectrum of severity of disease caused by the two subtypes. In contrast to previously reported data, subtype A predominated in each of the winter seasons studied within this community. We conclude that both subtypes circulate concurrently within the community during the winter. In hospitalized children both subtypes appear to cause a similar spectrum of disease. Both the concurrent circulation of RSV subtypes and the similar spectrum of illness pose for important considerations in the development of effective vaccines against this common respiratory agent in children. PMID- 1758738 TI - Undetected apnea and bradycardia in infants. AB - Despite routine monitoring, a number of prolonged apneic and bradycardic episodes were undetected in a group of infants in the neonatal intensive care unit (NICU). Sixty-one infants were evaluated by 12-hour pneumocardiograms at a post conceptional age of 35 +/- 3 (SD) weeks. Nursing documentation failed to detect 11 infants with prolonged apnea and bradycardia. Three of these infants were not detected in spite of increased awareness following in-service education. Such a lack of documentation may lead to improper medical management of infants at risk for pathologic apnea and suggests the need for more accurate documentation at the time of discharge. PMID- 1758739 TI - Inspiratory time and pulmonary function in mechanically ventilated babies with chronic lung disease. AB - To learn if increasing inspiratory time would improve pulmonary function in mechanically ventilated babies with chronic lung disease, we measured lung mechanics and alveolar ventilation at three inspiratory times: 0.4, 0.6, and 0.8 s. Nine babies were studied. Their mean birth weight was 875 g (range, 570-1,100 g), gestational age 27 (24-34) weeks, and age 7 (4-12) weeks. Their mean oxygen requirement was 40% (29-53), ventilator rate 33/min (20-40), and mean airway pressure 8 (5-10) cmH2O. Ventilator rate was kept constant; therefore expiratory time decreased and mean airway pressure and I:E ratio increased at longer inspiratory times. At 0.6 s and 0.8 s, when compared to 0.4 s, significant increases occurred in tidal volume (10.4, 10.1, and 8.4 mL/kg, respectively), dynamic lung compliance (0.68, 0.68, and 0.53 mL/cmH2O/kg, respectively), and alveolar ventilation (6.0, 6.3, and 4.7 mL/kg/breath, respectively). Airway resistance, anatomical dead space to tidal volume ratio, and functional residual capacity were similar at the three inspiratory times. Our findings suggest that an inspiratory time greater than or equal to 0.6 s (compared to 0.4 s) increases the effectiveness of mechanical ventilation for babies with chronic lung disease. PMID- 1758740 TI - Relationship of symptoms to lung function abnormalities in preterm infants at follow-up. AB - Recurrent respiratory symptoms are common in preterm infants in the first 2 years of life. The aim of this study was to determine the lung function abnormalities associated with such symptoms. Forty preterm infants, with a median gestational age of 29 weeks were studied at a median postnatal age of 12 months. Twenty-two suffered from recurrent symptoms, defined as wheezing and/or coughing on at least 4 days per week over the previous month. Lung function was assessed by measurement of functional residual capacity (FRC), using a helium gas dilution technique, and airway resistance (Raw) and thoracic gas volume (TGV) plethysmographically. No significant difference was found in TGV between symptomatic and asymptomatic infants, but the median FRC was lower (P less than 0.01), Raw higher (P less than 0.01), and FRC:TGV ratio lower (P less than 0.001) in the symptomatic infants. These lung function abnormalities in the symptomatic infants are suggestive of gas trapping. PMID- 1758741 TI - Importance of using lung function regression equations appropriate for ethnic origin. AB - Functional residual capacity (FRC) can be assessed reliably in young children using a helium gas dilution technique. The aim of the present study was to determine if differences in lung volume are found in asthmatic children of different ethnic origins. Eighty-eight children were studied, 53 of Caucasian origin and 35 of Afro-Caribbean origin. Their median age was 6.1 years (range, 5.3-9.0 years). FRC measured by helium gas dilution is reported as a percentage of predicted for height, using a published regression equation as well as regression equations appropriate for the ethnic origin of the child. In the majority of both groups FRC was elevated above the ethnically appropriate regression equation for healthy children. The Caucasian children apparently had higher FRCs than the Afro-Caribbean children if comparing the absolute lung volume, and if lung volume was expressed as percent of predicted for height, by a regression equation uncorrected for ethnic origin (P less than 0.02). This difference disappeared when ethnically appropriate regression equations were used. We conclude that lung volumes are similar in asthmatic children of different ethnic origin and that it is important to use ethnically appropriate regression equations. PMID- 1758742 TI - Hyperinflation in children with liver disease due to alpha-1-antitrypsin deficiency. AB - Fifty-nine patients (median age 6.0 years) with liver disease and ten healthy children without liver disease (median age 7.5 years) had serial measurements of functional residual capacity (FRC) over a period of at least 6 months. Twenty eight children with alpha-1-antitrypsin deficiency (A1ATD) tended to have higher lung volumes than 26 with extrahepatic biliary atresia (EHBA). Fifteen children had persistent hyperinflation (FRC greater than 120% predicted for height; 2 SD above the mean of controls); in five children (four with A1ATD) this was unresponsive to bronchodilator therapy. Two of the children with A1ATD who had persistent unresponsive hyperinflation on three serial measurements were only 3 and 4 years of age. No healthy child without liver disease was hyperinflated. These results suggest that A1ATD may be associated with lung function abnormalities even in very young children. PMID- 1758743 TI - Influence of sedation on the Hering-Breuer inflation reflex in healthy infants. AB - The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer inflation reflex (HBR). However, the persistence of this reflex beyond the early newborn period remains controversial. We have recently demonstrated that there is no change in the strength of this reflex during the first two months of life in healthy infants during natural sleep. Measurements beyond this immediate newborn period are difficult without sedation, but it is unclear whether sedation itself may influence this reflex. To investigate the influence of sedation, the HBR was measured in 66 healthy, full-term infants aged 4-8 weeks. Thirty-three infants were measured during natural sleep, and 33 after triclofos sodium sedation (75 mg.kg-1). The strength of the HBR was assessed from the change in expiratory time (TE) following brief end-inspiratory airway occlusion, as compared to TE during spontaneous breathing. The mean increase in TE following occlusion was 89.45% (SD, 29.8; range, 44-175) in infants sleeping naturally, and 92.42% (SD, 31.2; range, 34-179) in sedated infants. Using unpaired t tests, no statistically significant difference was found between groups (P = 0.7516). We conclude that the strength of the HBR in healthy infants is not influenced by sedation with triclofos sodium, in doses normally used for lung function testing. PMID- 1758744 TI - Comparison of six ECMO selection criteria and analysis of factors influencing their accuracy. AB - This study compared six extracorporeal membrane oxygenation (ECMO) selection criteria in 42 neonates and analyzed factors influencing the accuracy of outcome predictions. The sensitivity of the criteria in identifying fatal cases varied from 0.44 to 0.94 and the specificity of predictions of survival ranged from 0.42 to 0.69. The criterion having the highest sensitivity had the lowest specificity and conversely the criterion with the lowest sensitivity had the highest specificity. Overall accuracy of the criteria, as measured by the total number of correct outcome predictions, differed little among the criteria (23/42 to 27/42 correct predictions). Three factors influenced predictive accuracy: 1) a primary diagnosis of congenital diaphragmatic hernia (CDH) was associated with a greater mortality (P less than 0.001) and a significantly higher positive predictive value (PPV) for all criteria (P = 0.0009-0.012) than that seen in patients with other primary diagnoses; 2) calculating the alveolar-arterial oxygen gradient using an assumed, rather than measured barometric pressure, or estimating oxygenation index using a calculated, rather than a measured, mean airway pressure, increased false positive mortality predictions in non-CDH patients; and 3) requiring a peak inspiratory pressure (PIP) of at least 50 cm H2O in the definition of maximal medical management, rather than a PIP of 20-49 cm H2O, significantly increased the PPV for three of four criteria examined (P = 0.02 0.04). Awareness of these factors may facilitate the identification of neonates who need ECMO to survive. PMID- 1758745 TI - Psychological change associated with theophylline treatment of asthmatic children: a 6-month study. AB - Theophylline has been associated with a variety of behavioral side effects in asthmatic children. This study was a 6-month investigation of the relationship between theophylline treatment and psychological changes in 8 to 16 year old asthmatic children. Included were a group receiving theophylline (n = 19), a control group not receiving theophylline (n = 44), and a nonasthmatic control group (n = 24). The three groups had similar age, socioeconomic status, and IQ. The two groups of children with asthma demonstrated greater emotional dysfunction, characterized by tendency toward withdrawal and depression, than the nonasthmatic control group. Each of five assessment appointments (baseline and 1 week, 1 month, 3 months, and 6 months after beginning theophylline treatment) included measures of pulmonary function, attention, impulsivity, memory, fine motor control, activity level, self-reported mood, and parental observation of difficult behavior. Pulmonary functions were lower in the theophylline group at baseline but improved significantly after commencement of theophylline therapy. Over the 6-month interval, children in the theophylline group demonstrated improved scores on a laboratory measure of attention, while their parents reported increased conduct problems and hyperactivity. On the whole, psychological score changes were subtle, and no other between-group differences emerged in the remaining laboratory measures. PMID- 1758746 TI - Antineutrophil elastase activity in cystic fibrosis serum. AB - The antigenic concentrations of alpha-1-antitrypsin (alpha 1AT) were measured in 13 patients with cystic fibrosis (CF) and in 11 healthy subjects. Serum alpha 1AT was purified by immunoaffinity chromatography and the antielastase activity of the purified alpha 1AT was determined by measuring the molar ratio necessary to inhibit human neutrophil elastase (HNE). The association rate constant of alpha 1AT with HNE was determined in a timed assay. The capacity of CF serum alpha 1AT to form complexes with porcine pancreatic elastase was studied by polyacrylamide gel electrophoresis. Antigenic concentrations of alpha 1AT mumol/L were markedly increased in the serum of all patients with CF (61.9 +/- 4.3 mumol/L) in comparison to a reference standard (36.7 +/- 1.8 mumol/L; P less than 0.0001). CF serum alpha 1AT was fully active against HNE, and its association rate constant in the presence of HNE was similar to that of healthy subjects. In addition, CF serum alpha 1AT formed complexes with porcine pancreatic elastase that were electrophoretically indistinguishable from those of normal serum alpha 1AT. These results indicate that patients with CF have increased serum alpha 1AT concentrations and that this antiprotease, when purified from serum, functions normally. PMID- 1758747 TI - Comparison of FEV1 and transcutaneous oxygen tension in the measurement of airway responsiveness to methacholine. AB - The measurement of airway responsiveness in preschool children is hampered by the fact that most tests of airway caliber are difficult to carry out at a young age. Patient cooperation is only needed to a limited extent when transcutaneous oxygen tension (PtcO2) is used as an indicator of airway obstruction following bronchial provocation. In 51 children, aged 6-14 years with asthma we have measured PtcO2 and forced expiratory volume in 1 second (FEV1) concurrently after bronchial provocation, using increasing doses of methacholine administered with a De Villbiss 646 nebulizer and a French-Rosenthal dosimeter. The shapes of the dose response curves to PtcO2 and FEV1 show a close similarity. After methacholine challenge, the decrease in PtcO2 correlates highly with the decrease in FEV1. We conclude that in children a 20% decrease in PtcO2 can be used as a sensitive indicator of airway narrowing after methacholine challenge. PMID- 1758748 TI - Effect of nasal CPAP on thoracoabdominal motion in neonates with respiratory insufficiency. AB - Thoracoabdominal motion (TAM) profiles were determined in ten infants requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, in order to assess the influence of CPAP on chest wall function in infants with respiratory insufficiency. (TAM) was quantitated by respiratory inductive plethysmography, measuring relative motion of the rib cage and abdomen. Baseline pulmonary function (without CPAP support) was assessed from simultaneous measurements of transpulmonary pressure, air flow, and tidal volume. Measurements of (TAM) were acquired at baseline and at nasal CPAP levels of 0, 3, 5, and 8 cm H2O, in randomized order. Without CPAP, relative paradoxical motion occurred, i.e., the rib cage collapsed inward instead of expanding outward early in inspiration. With CPAP, TAM resembled the pattern in preterm infants, without lung disease. We found that nasal CPAP lowers the phase angle in infants with respiratory insufficiency (P less than 0.003), indicating improved synchrony of TAM. In addition, the improvement with nasal CPAP was related to the severity of pulmonary compromise at baseline. We speculate that changes in TAM associated with nasal CPAP arise from an interaction between pulmonary mechanics and an enhanced stability of the chest wall. In this context, the greater synchrony of TAM is suggestive of an improved breathing strategy. This may be a noninvasively obtainable marker of an effective nasal CPAP level in infants with altered pulmonary and chest wall mechanics. PMID- 1758749 TI - The long-term effect of high-frequency chest compression therapy on pulmonary complications of cystic fibrosis. AB - A high-frequency chest compression (HFCC) device for clearance of mucous secretions from airways was tested in 16 cystic fibrosis (CF) patients with significant improvement in pulmonary function for the HFCC period, which averaged 22 months per patient. The device consists of a variable air pulse delivery system and a non-stretch inflatable vest worn by the patient to cover the entire torso. The patients perform 30 minute therapy sessions divided into 5 minute periods at each of six frequencies. Individual patient therapy time per day ranged from 30 to 240 minutes. Frequencies used by each patient were determined by measuring air flow at the mouth and calculated volume expired per chest compression during tidal breathing while receiving HFCC at frequencies between 5 and 22 Hz at 1 Hz increments. The frequencies that produced the three highest flows and the three largest volumes were selected for each patient's therapy. Ninety-four percent of patients' regression line slopes for percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) became more positive during self-administered HFCC therapy as compared to slopes before HFCC therapy, when manual chest physical therapy was used. Two-sided t test showed that the mean slopes were more positive for FVC and FEV1 during HFCC therapy than for the manual chest physical therapy period before HFCC therapy. The significance level for both FVC and FEV1 was at P less than 0.001. PMID- 1758750 TI - Pilot study for the development of a monitoring device for ventilated children. AB - Airway pressure and air flow were measured at the endotracheal tube in 13 children on a variety of ventilators. These signals were stored for analysis on a computer. Further data sets were obtained after 24 hours or following major interventions. Air flow rate was integrated to give volume. Pulmonary resistance and elastance were obtained by multiple linear regression. Pressure-volume, pressure-flow and flow-volume loops were plotted. "Closed" pressure-volume and pressure-flow loops (by subtraction of the resistive or elastic pressure components, respectively) were also displayed, giving compliance and resistance loops. The loops from the initial data set were taken as the baseline, and loops from later data sets were superimposed to provide visual comparisons. Change in clinical status was reflected by the change in slope of compliance and resistance loops. A 30% change in compliance or resistance was easily observed. There was minimal interference with patient care. This pilot study demonstrates that changes in respiratory mechanics can be displayed safely and easily in ventilated patients using resistance and compliance loops. Further work is necessary to confirm the usefulness of real time of these displays. PMID- 1758751 TI - Endoscopic diagnosis and closure of a bronchopleural fistula. PMID- 1758752 TI - Was it just our problem, or yours too? Errors in body plethysmography, in infants, children, and adults. PMID- 1758753 TI - Respiratory mechanics of the piglet during the first month of life. AB - Piglets at 3, 14, and 30 days of age were studied to assess the postnatal changes in lung, chestwall, and total respiratory system compliance associated with normal growth. Static deflation compliance of the lung and total respiratory system increased significantly with age; there was no change in chestwall compliance. When normalized for body weight or lung volume, all measures of compliance tended to decrease with postnatal age. Measures of lung and chestwall compliance obtained with an end-inspiratory occlusion technique were less than the static compliance measures, but demonstrated the same relative changes with postnatal maturation. Chestwall compliance at 3 days of age was only 1.3 times greater than lung compliance and there was no significant change in this ratio with postnatal age. In contrast to the trend for the human infant, the piglet's chestwall at 3 days of age is stiff relative to the lung and does not become stiffer with age over the first 4 weeks of life. PMID- 1758754 TI - The effect of intravascular complement activation and brief episodes of hypoxia on protein in bronchoalveolar lavage fluid in C5 sufficient and deficient mice. AB - Our earlier investigations indicated that systemic complement activation with iv cobra venom factor (CVF) or infused zymosan-activated rabbit plasma or rabbit C5a does not significantly increase bronchoalveolar lavage albumin in rabbits (Am Rev Respir Dis 1982; 125:335-340); but that complement activation due to CVF combined with a brief episode of hypoxia increases lavage albumin and is associated with the presence of neutrophils for its expression (J Clin Invest 1985; 75:902-910). In order to determine if intravenous CVF and hypoxia cause similar alterations in mice, and to investigate the time course of the response as well as the importance of C5 fragments to the process, we challenged the B10.D2/nSn strain of C5 sufficient mice (C5+) and the congenic B10.D2/oSn strain of C5 deficient mice (C5-) with intravenous CVF, 15 min of 12% oxygen, or CVF followed by hypoxia. Neither C5+ nor C5- mice had significant increases in lavage protein after either CVF or hypoxia. However, the combined insults significantly increased lavage protein in C5+ but not C5- mice; polyacrylamide gel electrophoresis showed increased amounts of proteins of low and high molecular weights in lavage fluid from the C5+ strain. While the time course of abnormalities in mice was different from that in rabbits, both meclofenamate pretreatment and neutrophil depletion attenuated the increases in lavage protein after the combined insults in both animal species. Infusion of prostaglandin E2 (PGE2) with CVF in the C5+ mice also led to significant increases in lavage protein. We conclude that in mice, intravenous complement activation, as an isolated event, does not cause a significant increase in lavage protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758755 TI - Outcome of home care for technology-dependent children: success of an independent, community-based case management model. AB - Case management is important for successful home care of technology-dependent, respiratory-disabled children. Traditionally, the medical model of hospital-based home care and case management has been used for these children. The outcome may be different from when using independent, community-based home care and case management. We evaluated the results of 28 technology-dependent children [23 receiving mechanical ventilation and 5 receiving continuous positive airway pressure (CPAP)] from 8 hospitals, who utilized an independent, community-based, case management group to coordinate home care. After 26.3 +/- 20.6 months of follow-up, 13 children (46%) remained technology-dependent, 10 (36%) were technology-independent, and 5 (18%), all with neurologic dysfunction, had died. Only one death was caused by a complication of technology. All children with congenital anomalies (n = 4), primary pulmonary disease (n = 8), and neuromuscular disease (n = 4) survived, and 9 (56%) were weaned from technological support. Children with chronic respiratory failure secondary to central neurologic dysfunction (n = 12) did poorly: 5 died, 6 remained technology dependent, and only 1 became independent of technology. Children with neuromuscular diseases tended to use less home care nursing at a lower home care cost. Parent satisfaction was high among those who responded (82%), indicating that the child, siblings, and family were better off with the child at home. These outcomes suggest that community-based home care and case management is a reasonable alternative to the hospital-based model. PMID- 1758756 TI - Prevention of chronic pulmonary oxygen toxicity in young rats with liposome encapsulated catalase administered intratracheally. AB - The lungs and hearts of young rats exposed to 100% oxygen (O2) for 8 days (27 to 35 days of age) were studied following recovery in room air at 60 days of age using morphometric, biochemical, and physiological techniques. In an attempt to prevent chronic oxygen toxicity 153 rats had transtracheal catheters surgically implanted and were treated during the O2 exposure with daily intratracheal injections of liposome-encapsulated superoxide dismutase (SOD) and/or catalase (CAT). Oxygen exposure in this model results in chronic cardiopulmonary alterations which include pulmonary hypertension, right ventricular hypertrophy, and a decrease in number of pulmonary arterioles 25 to 50 microns in diameter with increased muscularization of their walls. The volume densities of the parenchyma, parenchymal air space, and the alveolar space are increased, while that of the combined alveolar ductal and respiratory bronchiolar space is decreased. Daily intratracheal administration of liposome-encapsulated CAT (160 U) during the O2 exposure prevented these chronic changes. Liposome-encapsulated SOD (110 U) or SOD (50 U) + CAT (70 U) did not appear to have a preventive effect. During the first 3 to 5 days following oxygen exposure the lung tissue enzymes SOD, CAT, and glutathione peroxidase markedly increased. We conclude that in the young rat animal model liposome-encapsulated CAT (160 U) given intratracheally during the period of O2 exposure is safe and will prevent the chronic vascular and parenchymal damage due to oxygen toxicity. PMID- 1758757 TI - Effect of prenatal cocaine on respiration, heart rate, and sudden infant death syndrome. AB - We studied 114 neonates by pneumocardiogram recordings in order to examine the effects of cocaine with and without opiate exposure on neonatal respiration, heart rate, apparent life threatening events (ALTE), and sudden infant death syndrome (SIDS). In full-term infants exposed to cocaine without opiates we found increased longest apnea duration and more episodes of bradycardia, but decreased periodic breathing and average heart rate than in control full-term infants. Term infants prenatally exposed to cocaine with opiates also had less periodic breathing. Preterm infants exposed to cocaine with and without opiates had decreased apnea density and periodic breathing compared with preterm controls. Discriminant analysis to determine whether perinatal asphyxia or exposure to other drugs could predict cardiorespiratory abnormalities showed no consistent relationship. In 72 of 114 infants available for follow-up, no ALTE occurred but two were lost to SIDS. Our data support the hypothesis that prenatal cocaine exposure may perturb, albeit subtly, the maturation of respiratory control, resulting in disruption of postnatal respiration. PMID- 1758758 TI - The effect of lung mechanics on gas transport during high-frequency oscillation. AB - With the general aim of obtaining clinically relevant information on the use of high-frequency oscillation (HFO), we examined the effects of altering oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on gas exchange in rabbits, both before and after altering the animal's pulmonary mechanics by saline induced lung injury. Twenty-seven combinations of f (5, 8, 12 Hz), VT (0.5, 1, 2 mL/kg), and Paw (5, 10, 13 cm H2O) were used. Acute pulmonary injury was induced by instilling 10 mL/kg of warm saline into the lung. Gas exchange was assessed by steady-state levels of arterial oxygen tension (PaO2) and carbon dioxide tension (PaCO2). Arterial PaO2 was independent of f or VT before or after lung injury; it was independent of Paw before injury but highly dependent on Paw after lavage. The difference was presumably related to lung volume recruitment. Arterial PaCO2 was dependent on f and VT but independent of Paw at any time. The relationship was modeled by the equation PaCO2 alpha fa. VTb where the exponents a = -0.4 and b = -0.6. Our technique of a standardized saline instillation gave a reproducible and stable model of lung injury. In damaged rabbit lungs the principles of HFO appear to be similar to conventional mechanical ventilation; oxygenation depends on Paw and inspired oxygen concentration, while CO2 removal is determined by f and VT. PMID- 1758759 TI - The effects of diuresis and transfusion on pulmonary function in children with thalassemia major. AB - Previous pulmonary function studies in subjects with thalassemia major (TM) who were on regular transfusion programs have demonstrated results ranging from small airway obstruction to a restrictive pattern. Ten subjects with TM were studied pre- and postdiuresis, and again 24 hr after transfusion, in order to evaluate the role of possible fluid overload in altering pulmonary function. Subjects underwent spirometry and had lung volume and flow volume curves (MEFVC) measured in a volume displacement plethysmograph while breathing air and a mixture of 80% helium and 20% oxygen (HeO2). Six patients had pulmonary mechanics measured with esophageal balloons in place. Baseline function was normal and no change occurred following diuresis. Following transfusion, the volume of isoflow (VisoV) decreased, but other parameters did not change. Subsequent analysis revealed 5 subjects with an initial VisoV greater than 20 (% FVC) but, paradoxically, less evidence of flow limitation in the small airways than those with a VisoV less than 20 (% FVC). Posttransfusion, in those subjects with an initially high VisoV, the Vmax25(air) tended to fall without a change of MEFVC in HeO2, resulting in a decreased VisoV. This was interpreted as evidence of subtle abnormalities in the small airways caused by volume expansion, raising doubts about the value of the VisoV as a measure of small airway disease. As a group, our subjects did not demonstrate any abnormalities in baseline function. Some subjects had mild flow limitation in small airway while other developed comparable levels of flow limitation following the volume expansion associated with transfusion. PMID- 1758760 TI - Hering-Breuer reflex in young asthmatic children. AB - The aim of this study was to assess if the Hering-Breuer reflex could be provoked in young children. Thirty asthmatic children with a mean age of 5.3 years and 18 healthy children with a mean age of 7.0 years were studied. The presence of the reflex was indicated by prolongation of the spontaneous expiratory time following application of continuous positive airways pressure (CPAP). The occurrence of the reflex was then related to age, compliance of the respiratory system (Crs) measured by weighted spirometry, functional residual capacity (FRC) determined by helium gas dilution, and the change in lung volume resulting from the application of CPAP. The asthmatic children in whom the Hering-Breuer reflex was observed tended to be younger (P less than 0.01) and the reflex was present in those children of both groups who had more compliant lungs (P less than 0.05). The FRC was not different in asthmatic children with and without the Hering-Breuer reflex, but healthy children in whom the reflex was present tended to have smaller lung volumes. The change in lung volume resulting from application of CPAP was significantly greater in those children of both groups in whom the reflex was present (P less than 0.01 asthmatics, P less than 0.02 healthy children). We conclude that the Hering-Breuer reflex may be provoked in young children. PMID- 1758761 TI - Esophageal pressure manometry in human infants. PMID- 1758762 TI - Tonal strength and melody recognition after long and short delays. AB - In a continuous-running-memory task, subjects heard novel seven-note melodies that were tested after delays of 11 sec (empty) or 39 sec (filled). Test items were transposed to new pitch levels (to moderately distant keys in the musical sense) and included exact transpositions (targets), same-contour lures with altered pitch intervals, and new-contour lures. Melodies differed in tonal strength (degree of conformity to a musical key) and were tonally strong, tonally weak, or atonal. False alarms to same-contour lures decreased over the longer delay period, but only for tonal stimuli. In agreement with previous studies, discrimination of detailed changes in pitch intervals improved with increased delay, whereas discrimination of more global contour information declined, again only for tonal stimuli. These results suggest that poor short-delay performance in rejecting same-contour lures arises from confusion that is based on the similarity of tonality between standard stimuli and lures. If a test item has the same contour and a similar tonality to a just-presented item, subjects tend to accept it. After a delay filled with melodies in other tonalities, the salience of key information recedes, and subjects base their judgments on more detailed pattern information (namely, exact pitch intervals). The fact that tonality affects judgments of melodic contour indicates that contour is not an entirely separable feature of melodies but rather that a melody with its contour constitutes an integrated perceptual whole. PMID- 1758763 TI - Auditory temporal summation in infants and adults: effects of stimulus bandwidth and masking noise. AB - A visually reinforced operant procedure was employed to determine the behavioral thresholds of 6- to 7-month-old infants and adults for stimuli of various bandwidths and durations. Experiment 1 compared absolute thresholds for broadband and 1/3-octave filtered clicks and 300-msec noise bursts. For adult subjects, the difference in threshold for clicks and noise bursts was quite comparable in the two bandwidth conditions, but infants' click-noise threshold differences were significantly larger for broadband than for 1/3-octave stimuli. In Experiment 2, 2-point threshold-duration functions were compared for 4-kHz tones and octave band noise bursts presented in backgrounds of quiet and continuous noise. Infants' threshold-duration function for octave-band noise bursts was significantly steeper than the comparable adult function in quiet, but not in masking noise. These results suggest that young infants may have particular difficulty detecting low-intensity broadband sounds when durations are very short. PMID- 1758764 TI - Local and global mechanisms of one- and two-dimensional orientation illusions. AB - One-dimensional (1-D) orientation illusions induced on a test grating by a tilted and surrounding 1-D inducing grating have a well-known angular function that exhibits both repulsion and attraction effects. Two-dimensional (2-D) orientation illusions are those induced on a test grating by 2-D image modulation, such as a pair of superimposed inducing gratings at different orientations, usually orthogonal (a plaid). Given the known angular functions induced by the plaid component gratings, two hypotheses were developed that predicted different plaid induced illusion functions. Hypothesis 1 states that the 1-D component-induced effects simply add linearly; Hypothesis 2 states that there is an additional mechanism that responds to the virtual axes of mirror symmetry of the plaid and adds to the effect. The data of two experiments were consistent with the predictions from the second hypothesis but not the first. Possible neural substrates of mechanisms that extract axes of symmetry are discussed; it is suggested that such global symmetry axes may underlie the perceived orientation of complex shapes. PMID- 1758765 TI - Partial information or facilitation? Different interpretations of results from speed-accuracy decomposition. AB - The speed-accuracy decomposition technique was developed by Meyer, Irwin, Osman, and Kounios (1988) to examine the time course of information processing. The technique allows for the estimation of the accuracy of guesses that are induced by the presentation of a response signal on a proportion of trials. Estimated guessing accuracy has been found to be above chance and to increase as time of guessing increases, suggesting that guesses are based on partial information that has accumulated prior to a response decision (sophisticated guesses). In this paper, a different interpretation of these data is presented. Results suggest that response signals may enhance the speed of regular processes, thereby violating the temporal-independence assumption that underlies the decomposition technique. As shown by Monte Carlo simulations, such facilitating effects of response signals can explain the results from the decomposition technique at least in part and possibly in full, even when guesses are actually at chance accuracy (pure guesses). The pure-guess model was supported by the results from an experiment designed to test between the alternative interpretations. These results point to the need for great caution in the attempt to infer the time course of information processing from guessing accuracies as estimated by the speed-accuracy decomposition technique. PMID- 1758766 TI - Subcategorical phonetic mismatches and lexical access. AB - The place of phonetic analysis in the perception of words is unclear. While some theories assume fully specified phonemic strings as input, other theories assume that little analysis occurs. An earlier experiment by Streeter and Nigro (1979) produced evidence, based on auditorily presented words with misleading acoustic cues, that lexical decisions were based on mostly unanalyzed patterns, since word judgments were delayed by misleading information whereas nonword judgments were not. The present studies expand that work to a different set of cues, and to cases in which the overriding cue came first. An additional task, auditory naming, was used to examine the effects when the decision stage is less demanding. For the lexical decision task, misleading information slowed the responses, for both words and nonwords. In the auditory naming task, only the slower responses were affected. These results suggest that phonetic conflicts are resolved prior to lexical access. PMID- 1758767 TI - Spatial judgments of exocentric extents in an open-field situation: familiar versus unfamiliar size. AB - Carlson and Tassone (1971) found that an object of familiar size presented in an outdoor setting and viewed at an appreciable distance is judged to be more distant than an unfamiliar object. Three experiments examined whether object familiarity also affects spatial judgments of exocentric extents presented under conditions comparable to those of Carlson and Tassone's experiments. The markers of the extents were either familiar or unfamiliar objects. In Experiment 1, subjects reproduced the perceived extents of depth intervals by adjusting a comparison egocentric extent, and in Experiment 2, subjects also compared the relative depths of two equally long extents. In Experiment 3, the two equally long extents were presented in the subjects' frontoparallel plane, and the subjects reported which of these two extents appeared longer and farther away. The results of these experiments indicate that familiar size does not affect the perceived depths or lengths of exocentric extents viewed under naturalistic conditions. PMID- 1758768 TI - Second-order relational properties and the inversion effect: testing a theory of face perception. AB - Recognition of faces is more severely impaired by inversion than is recognition of other types of objects. This was originally interpreted as evidence for the existence of special face-recognition mechanisms. Recently, Diamond and Carey (1986) attributed the inversion effect to the use of second-order relational properties that are important for, but not unique to, face recognition. According to their hypothesis, face recognition differs from the recognition of most other objects in its dependence on second-order relational properties. This hypothesis was tested in two experiments by comparing the effects of inversion on the identification of dot patterns that differed in the extent to which they required the encoding of second-order relational properties. Identification of the second order relational patterns was not more disrupted by inversion than was identification of first-order patterns. These results fail to support the hypothesis that second-order relational properties are responsible for the inversion effect. PMID- 1758769 TI - The relationship between eye position and egocentric visual direction. AB - Hering's model of egocentric visual direction assumes implicitly that the effect of eye position on direction is both linear and equal for the two eyes; these two assumptions were evaluated in the present experiment. Five subjects pointed (open loop) to the apparent direction of a target seen under conditions in which the position of one eye was systematically varied while the position of the other eye was held constant. The data were analyzed through examination of the relationship between the variations in perceived egocentric direction and variations in expected egocentric direction based on the positions of the varying eye. The data revealed that the relationship between eye position and egocentric direction is indeed linear. Further, the data showed that, for some subjects, variations in the positions of the two eyes do not have equal effects on egocentric direction. Both the between-eye differences and the linear relationship may be understood in terms of individual differences in the location of the cyclopean eye, an unequal weighting of the positions of the eyes in the processing of egocentric direction, or some combination of these two factors. PMID- 1758770 TI - Fixation-point offsets reduce the latency of saccades to acoustic targets. AB - If an observer's fixation point is extinguished just prior to the onset of a peripheral target, the latency to saccade to that target is reduced. We show that this "gap effect" is not specific to visual targets. Observers made saccades to a light flash or to a white-noise burst. A warning tone was presented on every trial to control for the possible warning effect of the fixation-point offset. For both target modalities, saccade latencies were significantly reduced when the fixation point was extinguished 200 msec prior to the target onset. Implications of this outcome for interpretations of the gap effect are considered. It is argued that the presence of a gap effect for tones, in conjunction with previous findings, is consistent with the hypothesis that the gap effect is produced by a facilitation of premotor processes in the superior colliculus. PMID- 1758772 TI - Arabic children's pain descriptions. AB - A convenience sample of 60 children, aged five to 12 years, reporting to Kuwait government hospital emergency departments was studied. All were native Arabic speakers. Our aim was to compare the diagnostic usefulness of the pain information provided by children and by accompanying adults when interviewed under standard emergency department conditions. Children were asked to describe their current pain and how it had changed and to signify pain intensity using a 10-point visual analog scale (VAS). Comparable data were then collected from the accompanying adult. Senior clinicians rated these verbal and VAS descriptions for their usefulness in arriving at a diagnosis. Most children provided useful pain information. Mothers received consistently higher scores for their VAS descriptions than their children did; otherwise, the pain data provided by adults were not judged to be significantly more useful. When clinicians and teachers were asked to differentiate which data they thought had been provided by a child and which by the accompanying adult, nearly half of their decisions were wrong. PMID- 1758771 TI - Visual search, visual streams, and visual architectures. AB - Most psychological, physiological, and computational models of early vision suggest that retinal information is divided into a parallel set of feature modules. The dominant theories of visual search assume that these modules form a "blackboard" architecture: a set of independent representations that communicate only through a central processor. A review of research shows that blackboard based theories, such as feature-integration theory, cannot easily explain the existing data. The experimental evidence is more consistent with a "network" architecture, which stresses that: (1) feature modules are directly connected to one another, (2) features and their locations are represented together, (3) feature detection and integration are not distinct processing stages, and (4) no executive control process, such as focal attention, is needed to integrate features. Attention is not a spotlight that synthesizes objects from raw features. Instead, it is better to conceptualize attention as an aperture which masks irrelevant visual information. PMID- 1758773 TI - Are parents accurate in their assessment of fluid volumes? AB - Ingestions constitute a common problem in pediatric emergency medicine. Management decisions are frequently based on parental assessments of the amount of the ingested material. The purpose of this study was to examine the accuracy of parental estimates of fluid volumes. One hundred parents of children seen in an outpatient clinic and emergency department were asked to estimate fluid volumes in four containers. There were no significant differences (P greater than 0.05) in the accuracy of fluid volume assessment between younger and older parents, between participants with and without high school education, or between parents with one or more children. While most parents are accurate in their fluid volume estimates, 14.5% of the assessments were overestimates of over 300% of the actual volume. In view of our findings, caution should be used when management decisions are being based on parental fluid volume estimates. PMID- 1758774 TI - Extreme leukocytosis in patients presenting to a pediatric emergency department. AB - We determined the frequency and clinical significance of white blood cell (WBC) counts greater than or equal to 25,000/microliters in children presenting to an emergency department (ED) and defined a degree of leukocytosis which might be considered extreme in this setting. Records of all patients seen in the ED between February 1985 and December 1986 with WBC counts greater than or equal to 25,000/microliters were identified. Each patient was paired with the chronologically nearest patient with a WBC count between 15,000 and 25,000/microliters. Of the total WBCs obtained, 5.8% were greater than or equal to 25,000/microliters; only 1% were greater than or equal to 35,000/microliters. Eighteen percent of patients with counts greater than or equal to 25,000/microliters had a serious disease, and 6% had bacteremia. Twenty-six percent of patients with counts greater than or equal to 35,000/microliters had a serious disease, and 10% had bacteremia. On the basis of infrequency and severity of illness, we suggest that, in children presenting to a pediatric emergency department, WBC counts greater than or equal to 35,000/microliters be considered extreme leukocytosis. PMID- 1758775 TI - Adenosine in the emergency management of supraventricular tachycardia. AB - In summary, adenosine is highly effective in terminating paroxysmal supraventricular tachycardia, and its very short half-life and benign side effects make it a promising alternative to other modes of therapy presently used. Further controlled prospective studies are needed before adenosine can become the drug of choice in the management of paroxysmal supraventricular tachycardia in children. PMID- 1758776 TI - The radiolucent wooden foreign body. AB - Wooden foreign bodies in the extremities are frequently not suspected at initial presentation. Most often, these foreign bodies are not visualized radiographically. Xeroradiography, ultrasound, computed tomography, and MRI have been described as useful adjuncts in foreign body detection and localization. In our case, a truly radiolucent wooden foreign body was well visualized on plain radiographs. The atypical appearance resulted in misinterpretation, and proper diagnosis and treatment were delayed. PMID- 1758777 TI - Reye's syndrome associated with acute myocarditis and fatal circulatory failure. AB - We describe an eight-month-old infant who had an unusually fulminant and fatal course of Reye's syndrome. The patient died 36 hours after admission because of irreversible circulatory failure not associated with clinical symptoms of increased intracranial pressure or cerebral herniation. Autopsy revealed the pathognomonic fatty degeneration of the liver and heart of Reye's syndrome, but the brain was normal. In addition, a marked inflammatory infiltration of the myocardium was also observed, which indicated that acute myocarditis had been the preceding underlying disease. This case report emphasizes the fact that the viral prodrome preceding Reye's syndrome may not be as benign as often observed with influenza and varicella. Acute myocarditis and Reye's syndrome are also a combination which may result in fatal cardiovascular collapse. PMID- 1758778 TI - Centipede ingestion by a six-month-old infant: toxic side effects. AB - Centipedes are a common household arthropod whose bite usually causes only local reactions. Ingestion of centipedes has not been previously reported. This article reports the case of a six-month-old infant who ingested a centipede of the Scutigera morpha species and had systemic side effects probably due to systemic absorption of its venom. The child recovered spontaneously after 48 hours. This case illustrates that toxic effects may be noted after ingestion of arthropods and that in this type of centipede no active intervention may be necessary. PMID- 1758779 TI - Intraspinal hemorrhage in a child with factor XIII deficiency. AB - The rarity of spinal cord injuries and hemorrhages and of fibrin-stabilizing factor XIII deficiency during childhood has induced us to report the case of this two-year-old boy with factor XIII deficiency who presented with cervical intraspinal hemorrhage between the C4 and C7 levels as well as paraplegia presumably following a minor trauma. The findings in this patient, who was brought in two weeks after the appearance of the first symptoms, indicate the importance of early diagnosis and early intervention to minimize the extent of the damage from the injury in such cases. The case also points to the need for close follow-up of patients with factor XIII deficiency for CNS bleeding. PMID- 1758780 TI - Should corticosteroids be used in the treatment of bacterial meningitis? Pro and con. PMID- 1758781 TI - Infusion pumps. PMID- 1758782 TI - Life-threatening infections. PMID- 1758783 TI - Acute respiratory distress in a young infant. PMID- 1758784 TI - The use of slap wrist ("snap-wrap") bracelets by young school-aged and preteen children. PMID- 1758785 TI - The cultural context of polio biographies. AB - Cultural contexts influence the ways individuals interpret and experience functional losses associated with post-polio sequelae. Using in-depth multiple interview case studies from two National Institute on Aging projects, the concept of "biographies" is presented to place the individuals' polio-related experiences within the context of their lives. Two major cultural contexts shape the construction of polio biographies: normative life course expectations and developmental tasks; and traditions associated with polio recovery and rehabilitation. The authors identify key dimensions of personal concern among polio survivors that can be used as entrance points for effective clinical intervention and to promote treatment compliance. PMID- 1758786 TI - The psychology of polio as prelude to post-polio sequelae: behavior modification and psychotherapy. AB - Even as the physical causes and treatments for post-polio sequelae (PPS) are being identified, psychological symptoms--chronic stress, anxiety, depression, and compulsive, Type A behavior--are becoming evident in polio survivors. Importantly, these symptoms are not only causing marked distress but are preventing patients from making the lifestyle changes necessary to treat their PPS. Neither clinicians nor polio survivors have paid sufficient attention to the acute polio experience, its conditioning of life-long patterns of behavior, its relationship to the development of PPS, and its effect on the ability of individuals to cope with and treat their new symptoms. We describe the acute polio and post-polio experiences on the basis of patient histories, relate the experience of polio to the development of compulsive, Type A behavior, link these behaviors to the physical and psychological symptoms reported in the National Post-Polio Surveys, and present a multimodal behavioral approach to treatment. PMID- 1758787 TI - Effect of treatment and noncompliance on post-polio sequelae. AB - In this study of 77 patients with post-polio sequelae (PPS), symptoms and manual test scores on initial evaluation were compared with those at subsequent follow up evaluations. Patients were divided into three groups based on the degree to which they had complied with clinically recommended interventions: compliers, partial compliers, and noncompliers. At the end of the follow-up period (2.2 +/- 1.2 years), the mean muscle function scores of the entire study group had declined -1.5%, which represented a decline of -0.7% annually. On follow-up evaluations, the complier group had realized an improvement or resolution of post polio symptoms, and also an improvement in muscle function of +0.6% annually. The partial complier group had realized either no improvement, or improvement in post polio symptoms, but showed a further decline in muscle function of -3.0%, or an annual decline of -1.3%. The noncomplier group showed either no change, or a worsening of post-polio symptoms, and also showed a further decline in muscle function of -4.1%, which represented an annual decline of -2.0%. PMID- 1758788 TI - Assessment and differential diagnosis for post-polio syndrome. PMID- 1758789 TI - Activity and post-polio fatigue. AB - Fatigue was studied in 12 subjects with post-polio sequelae (PPS). Results of the Fatigue Severity Scale (FSS) demonstrated a mean score of 4.8 +/- 1.6 (non disabled scores = 2.3 +/- 0.7). The Human Activity Profile (HAP) was not sensitive enough to measure fatigue. Fifty percent of subjects scored below the first percentile based on age and sex matched norms. The Activity Record (ACTRE) results revealed that subjects spent 5% of their time resting and 1% in planning or preparation activities. Fatigue peaked in the late morning or early afternoon and was relieved by rest periods. Use of energy conservation and work simplification skills along with frequent rest periods was suggested as a possible method for managing PPS fatigue. PMID- 1758790 TI - Energy conservation, occupational therapy, and the treatment of post-polio sequelae. AB - Individuals experiencing post-polio sequelae (PPS) are usually advised to make significant lifestyle changes to lessen symptoms and prevent further decline in function. These individuals have spent most of their lives equating success with over-achievement and find it difficult to implement such recommendations. As specialists in energy conservation and work simplification, occupational therapyists increasingly are being called on to evaluate and treat these patients. Over the past 2 years, an occupational therapy educational program has been developed to educate patients about their condition and about ways to implement lifestyle changes while preserving the ability to do valued activities. This article describes the components of a thorough occupational therapy evaluation and the design and functional outcomes of a successful occupational therapy educational program to treat PPS. PMID- 1758791 TI - Effect of modified aerobic training on movement energetics in polio survivors. AB - Given that individuals with disabilities may be unable to achieve maximal oxygen uptake in an exercise test and that maximal exercise testing may cause increased fatigue, pain, and muscle weakness, we examined the role of submaximal exercise testing and training based on objective as well as subjective parameters in polio survivors. Experimental (N = 7) and control subjects (N = 13) were tested before and after a 6-week period. The experimental subjects participated in a 6-week exercise training program for 30 to 40 minutes, three times a week. The program consisted of treadmill walking at 55% to 70% of age-predicted maximum heart rates; however, exercise intensity was modified to minimize discomfort/pain and fatigue. Neither objective nor subjective exercise responses were significantly different in the control group over the 6 weeks. No change was observed in cardiorespiratory conditioning in the experimental group. However, movement economy, which is related to the energy cost of walking, was significantly improved; and walking duration was significantly increased at the end of training. Modified aerobic training may have a role in enhancing endurance and reducing fatigue during activities of daily living in polio survivors. PMID- 1758792 TI - The effects of long-term non-fatiguing resistance exercise in subjects with post polio syndrome. AB - Measures of torque were used to evaluate changes in muscle strength and endurance in 17 patients with post-polio syndrome who did prescribed resistance exercise for up to 2 years. Exercise compliance averaged 75%, with 16 subjects increasing the weight lifted in training. Maximum torque was significantly increased in the exercised muscle compared to the control muscle; no difference was seen in muscle endurance. Individuals with post-polio syndrome can increase muscle strength by doing non-fatiguing resistance exercise, but they should undergo quantitative testing of muscle strength a minimum of every 3 months to guard against overwork weakness. PMID- 1758793 TI - Post-polio fatigue: a 31P magnetic resonance spectroscopy investigation. AB - Changes in high energy phosphates (HEP) and intramuscular pH during exercise were measured in 17 patients with post-polio fatigue and in 28 healthy controls using 31P magnetic resonance spectroscopy (MRS). Subjects performed a dynamic hand grip exercise at low and high intensity. Mean changes in the HEP and pH showed no significant differences between the groups, although the post-polio group's response was highly variable. Six patients showed evidence of a lower lactate accumulation during the high intensity exercise when compared with controls. These data suggest that the whole body fatigue experienced by polio survivors is not related to any systemic metabolic abnormality. PMID- 1758794 TI - Polioencephalitis, stress, and the etiology of post-polio sequelae. AB - Post-mortem neurohistopathologies that document polio virus-induced lesions in reticular formation and hypothalamic, thalamic, peptidergic, and monoaminergic neurons in the brain are reviewed from 158 individuals who contracted polio before 1950. This polioencephalitis was found to occur in every case of poliomyelitis, even those without evidence of damage to spinal motor neurons. These findings, in combination with data from the 1990 National Post-Polio Survey and new magnetic resonance imaging studies documenting post-encephalitis-like lesions in the brains of polio survivors, are used to present two hypotheses: 1) polioencephalitic damage to aging reticular activating system and monoaminergic neurons is responsible for post-polio fatigue, and 2) polioencephalitic damage to enkephalin-producing neurons is responsible for hypersensitivity to pain in polio survivors. In addition, the antimetabolic action of glucocorticoids on polio damaged, metabolically vulnerable neurons may be responsible for the fatigue and muscle weakness reported by polio survivors during emotional stress. PMID- 1758795 TI - The link between rehabilitation and orthopedics. PMID- 1758796 TI - Insulin resistance and hypertension--implications for treatment. PMID- 1758798 TI - Infection in exacerbations of asthma: views of different groups of practitioners. AB - A questionnaire designed to elucidate views on the frequency of infection in asthma and its management was circulated to general practitioners, general physicians, paediatricians and respiratory physicians in the north of England. On the whole, general practitioners agreed with the general physicians and paediatricians with respiratory physicians. The generalists, and to a lesser extent the specialists, tended to overestimate the risk of bacterial infection, which was perceived to be a particular risk following viral infection in intrinsic asthma. This resulted in more frequent prescription of antibiotics than is justified by the published evidence. There was a tendency for frequent prescribers of antibiotics to withhold corticosteroids. If prescribing habits are to be altered, education will have to be directed at those responsible for acute admissions to hospital as well as at general practitioners. PMID- 1758799 TI - Asian endoscopies: is there a difference? AB - In 1988 2062 adults had their first oesophagogastroduodenoscopy at Leicester General Hospital, of whom 224 (10.9%) were Asian. A greater proportion of the Asian patients were less than 45 years old (46% vs 24%), which reflects the age distribution of the local population. When the findings at oesophagogastroduodenoscopy were analysed in two age groups (less than or older than 45) there were no differences between the races in the younger group. However, in the older group duodenal disease was significantly more common in the Asians (P less than 0.001) whereas gastric disease was more common in Caucasians (P less than 0.05). The incidence of cancer was much lower in the Asians. PMID- 1758797 TI - General surgery. PMID- 1758800 TI - The practice of rectal examination. AB - Rectal (both digital and rigid sigmoidoscopic) examination is an important part of the clinical examination. The aim of this study was to find out the opinions of the patients to this routine examination at the time of referral by their general practitioner and during their first hospital interview. Assessment of the value for the rectal examination was also examined. We questioned 103 patients attending their second out-patient interview through a simple questionnaire. We discovered that patients considered awareness and explanation important: patients preferred to be told of the possibility of rectal examination prior to hospital consultation. Explanation of the method and reason was expected from hospital doctors. Formal consent was expected; informed verbal consent should be sufficient. Where logistically possible, a chaperone should always be present. Rectal examination would have facilitated the diagnosis in 47% of the patients examined. Thus, rectal examination should be performed on all patients where symptoms are referable to the lower gastrointestinal tract and where a possible diagnosis may be made or facilitated. PMID- 1758801 TI - Fatal splenic sequestration crisis in adult sickle cell-beta thalassaemia. AB - Fatal acute splenic sequestration crisis in an adult patient with sickle cell beta+ thalassaemia is described. To our knowledge fatal splenic sequestration in adult sickle cell-beta thalassaemia has not been previously reported. PMID- 1758802 TI - Rapid onset of blindness due to meningeal carcinomatosis from an oesophageal adenocarcinoma. AB - We report a 49 year old man who presented with left leg weakness, frontal headache, impaired concentration and dysphagia. He was thought to have a benign oesophageal stricture on barium swallow and oesophagoscopy though this was not initially biopsied. During admission his vision deteriorated so that he could only recognize bright light. Repeat oesophagoscopy demonstrated an oesophageal adenocarcinoma. The diagnosis of meningeal carcinomatosis was confirmed at post mortem. Sudden bilateral blindness is a common feature of meningeal carcinomatosis but, as this is rare, it is not commonly considered in the differential diagnosis of visual loss. The visual loss can be explained by vascular insufficiency in association with tumour cuffing of the subarachnoid space of the optic nerve sheath, by neuronal toxins, or other, as yet unknown, mechanisms. PMID- 1758803 TI - Rhabdomyolysis associated with cranial diabetes insipidus. AB - Rhabdomyolysis has been reported to be associated with hyperosmolality in diabetic ketoacidosis and non-ketotic hyperosmolal state. Whether the rhabdomyolysis was due to hyperosmolality per se or whether hyperglycaemia also played a role is not clear. We hereby report a case of cranial diabetes insipidus with hypernatraemia and hyperosmolality complicated by rhabdomyolysis. None of the known risk factors, such as coma, hypokalaemia, hypophosphataemia, diabetic ketoacidosis or non-ketotic hyperosmolality, were present in this patient. We believe that severe hyperosmolality per se is an important predisposing factor for non-traumatic rhabdomyolysis, and serum muscle enzymes should be closely monitored in the management of patients with diabetes insipidus. PMID- 1758804 TI - Coronary heart disease in diabetes mellitus--antecedents and associations. PMID- 1758805 TI - The chronic cardiovascular risk factor syndrome (syndrome X): mechanisms and implications for atherogenesis. PMID- 1758806 TI - The smoker with diabetes: a difficult challenge. PMID- 1758808 TI - Hypertension in non-insulin dependent diabetes mellitus and its management. PMID- 1758807 TI - Treatment of diabetes: the effect on serum lipids and lipoproteins. PMID- 1758809 TI - Specific lipid lowering therapy in the management of diabetes. PMID- 1758810 TI - Profound prolonged hypotension following captopril overdose. PMID- 1758811 TI - Percutaneous endoscopic gastrostomy in elderly patients. PMID- 1758812 TI - Clinical tutors and surgical tutors. PMID- 1758813 TI - Morphine myths: sedation, tolerance, addiction. AB - Morphine and other strong opioids are still, more than 180 years after the syntheses of morphine, not adequately used in clinical practice and many patients suffer unnecessarily severe pain in consequence. Governments limit morphine usage by legal restrictions. The underuse of morphine and its restriction in many countries is mostly due to prejudice and myths which clinical experience does not show to be true. Morphine is a very safe drug, correctly prescribed in chronic pain therapy, the only severe side effect being constipation. PMID- 1758814 TI - The incidence of cancer pain and improvement of pain management in Japan. AB - A nation-wide survey (1987) of cancer pain and analgesic methods showed that the incidence of pain in the terminal stage was in the range of 68 to 72% without any significant difference between hospital groups. Irrespective of the stage of illness, a certain analgesic effect was obtainable with oral/parenteral use of opioids. As a result of a year-to-year comparison of pain in cancer clinics, it was found that the rate of complete pain relief has increased for all stages of illness, especially in the terminal stage. Here the rate of complete pain relief steadily increased from 37.8% in 1986 to 42.7% in 1987 and 48.6% in 1988. Propagation of WHO-advocated cancer pain therapeutics has led to an improvement of the rate of pain relief in the terminal stage. Marketing of MS Contin tablets resulted in a dramatic increase in the consumption of morphine, but there was no increase in the rate of pain relief due to poor measures to counter adverse reactions, and to administration of morphine in insufficient doses. The consumption of morphine for medical use increased year by year, but a greater number of doctors experienced in the use of opioids would further improve the management of pain. To realize that, it would be necessary to incorporate terminal care into medical education programmes as soon as possible. Further efforts will be required for extensive research and propagation of analgesic methods in various fields including education in medicine, science of nursing and postgraduate education. PMID- 1758815 TI - Pain treatment in gynaecological cancer. AB - Women suffering from gynaecological malignancies are highly represented in patients with cancer pain: 19.3% of tumour related deaths in females are caused by breast carcinoma, 7.1% by carcinoma of the uterus, 6.7% by ovarian carcinoma and 2.3% by other malignant gynaecological tumours. These tumours may give rise to severe pain due to osseous metastases, nerve or plexus infiltration, soft tissue infiltration and (in the case of ovarian carcinoma) obstruction of the gastrointestinal tract. The experience represented in the literature and our own experience demonstrate that there are very effective measurements of symptom control in cancer pain. Based on the results of a specialized cancer pain control clinic at the University of Dusseldorf, Germany, recommendations will be given for the treatment of cancer pain. The use of nonsteroidal anti-inflammatory drugs, weak and strong acting opioids and co-analgesics in relation to the different sites of metastases as well as neurosurgical and anaesthetic manoeuvres are the subject of the presentation. Furthermore an overview of the psycho-social care of cancer patients by the social worker and the priest will be given. PMID- 1758816 TI - Relationship between plasma concentration of morphine and analgesic effectiveness. AB - Morphine is a key drug for cancer pain management. In this study, we analyzed plasma morphine concentration in cancer patients who received continuous morphine drip and/or oral administrations of morphine: (1) The plasma concentration of morphine varied widely in patients whose pain was satisfactorily controlled at a constant dosage of morphine. The absolute value of the plasma concentration of morphine necessary for effective pain control could not be estimated; (2) When MS Contin was given at the doses 20 mg, 30 mg, 40 mg, the plasma concentration of morphine increased with increasing dose. Thus, when the dose was increased according to the severity of pain, the plasma concentration of morphine increased and in turn an analgesic effect was obtained; (3) In those patients who had difficulty in taking oral preparations and/or blocked intestines, plasma concentration of morphine following oral administration was relatively low causing an unsatisfactory analgesic effect. However, by changing from oral administration to continuous drip infusion, the plasma concentration of morphine became higher and pain relief was obtained; (4) Continuous drip infusion of morphine progressively increased plasma concentration of morphine in parallel with the increase in the dose of morphine if the patients had no pleural effusion, ascites, and/or oedema. In contrast, plasma morphine concentration in patients with pleural effusion, ascites, and/or oedema was about half of that observed in patients who have normal distribution area. The rapid development of pleural effusion and ascites lowers the blood level of morphine; (5) To use the plasma concentration of morphine as an index for the analgesic effect, it is essential to develop a method to measure the plasma concentration of morphine rapidly. PMID- 1758817 TI - Morphine at gramme doses: kinetics, dynamics and clinical need. AB - The MS Contin tablet 200 mg (controlled release morphine sulphate) provides an equivalent rate and extent of absorption to two MS Contin tablets 100 mg. The characteristics of controlled release from this higher strength formulation are also consistent with those of the 100 mg tablet. The level of analgesia provided during the early post-dosing period, at the end of the dosing period and overall over the twelve hour interval were also equivalent between the preparations. The addition of the MS Contin tablet 200 mg to the existing range will facilitate oral dosing in patients requiring large doses of morphine. This extension to the range will increase the choice available to the clinician and provide a natural progression for those patients requiring a step-up in the dose titration procedure. PMID- 1758818 TI - Morphine pharmacokinetics and analgesia after oral administration. AB - The well established use of oral morphine in the treatment of chronic cancer pain has developed empirically and a knowledge of its pharmacokinetics is not necessary in order to use the drug effectively. However recent information about the pharmacokinetics of morphine may help resolve the controversy about oral to parenteral relative potency ratios, and may also in the future shed some light on the problem of patients whose pain does not respond to morphine. PMID- 1758819 TI - Family factors influencing cancer pain management. AB - The purpose of this study was to describe family factors which influence cancer pain. Previous research has focused on the patients' and professional caregivers' perspective of pain. Cancer pain is an intense burden on the entire family as well as on the patient. Findings of the study demonstrate family perceptions of pain, caregiver burden associated with pain, caregiver moods and differences in caregiver experiences of pain between three sites of care including a hospice, a community hospital and a cancer centre. Understanding the perspective of the family caregivers and their role in pain management can assist health care providers in management of the patient's pain. PMID- 1758820 TI - Morphine: myths, morality and economics. AB - It is a tragedy that morphine is scarcely available for between 1.3 and 2.5 billion people whilst 3.5 million cancer patients suffer needlessly. In only 10 countries is its consumption rising, in many more only codeine consumption shows an increase, and in many areas even in the Western world prescribing is grossly limited, fears of psychological addiction persist, professional education of doctors and nurses in analgesia remains minimal and too much importance is attached to expensive sophisticated methods of administration. Doctors have a professional and a moral responsibility to press for improved morphine availability in the most useful and economical forms worldwide. PMID- 1758821 TI - Morphine sulphate tablets in hospice practice. AB - Sustained release morphine sulphate tablets (MST Continus), have been available for use in New Zealand since 1984. They have become the major opioid in use for palliative and terminal care. The Mary Potter Hospice was founded in 1978 and is New Zealand's largest hospice. The records of 100 consecutive patients admitted to the Mary Potter Hospice Programme who were prescribed morphine sulphate tablets (MST) were collected prospectively in order to document current hospice usage of MST. It was found that MST was widely tolerated and was highly successful in controlling pain in the majority of patients. There was a wide dosage range and the dose required appears independent of pathology, age of patient or previous analgesic exposure. It was rapidly apparent when MST had been employed inappropriately. The commonest reasons for cessation of medication were death of the patient or their moribund state. Contrary to expectations nausea and vomiting were not frequent causes of stopping medication, neither were confusion nor altered states of consciousness. The advantages of MST were demonstrated giving evidence for the reasons this agent is now the principle opioid employed in palliative and terminal care in the Mary Potter Hospice. PMID- 1758822 TI - A clinical survey of controlled-release morphine sulphate for cancer pain relief in a Japanese hospice. AB - Seventy-six cancer patients were studied on the use of controlled-release morphine sulphate (MS Contin) for cancer pain relief in the hospice of Yodogama Christian Hospital in Japan. The mean initial and maximum dosages were 81.4 mg and 178.6 mg respectively. While 46 patients (61%) did not need an increase in the initial dosage, 26 patients (34%) needed an increase ranging between 8 and 125%. Four patients (5%) required an increment of more than 500% of the initial dosage, because of apparent nerve involvement. This clinical survey showed that the total effectiveness was 92% and that 90% of the patients could experience control of pain with a daily dosage of 240 mg or less of MS Contin. Side effects observed were as follows: drowsiness 21%, nausea 11%, vomiting 8%, constipation 8%, confusion 7%, hallucination 3%. In conclusion, MS Contin offers effective cancer pain relief with minimal side effects in the majority of patients. PMID- 1758823 TI - Experience with a controlled-release oral morphine for cancer pain management. AB - An open pilot study was performed to assess the analgesic efficacy and acceptability of a controlled-release oral morphine preparation. Between March 1989 and August 1990, 50 patients were treated with MS Contin (morphine sulphate tablets-MS Continus) for the pain caused by advanced cancer. The participants consisted of 28 males and 22 females ranging in age from 8 to 78 years (median 52 years). Twenty-two patients were actively receiving either cancer chemotherapy (15 patients), radiotherapy (2 patients), combined chemoradiotherapy (3 patients) or hormonal treatment (2 patients). Most of the subjects had pain caused by visceral disease and bone metastasis. A combination of causes was also present in 19 patients. The patients had a wide variety of cancers the most common being stomach cancer. In 24 patients, concomitant non-opioid or non-morphine opioid analgesics were combined with MS Contin. The median duration between cancer diagnosis and MS Contin initiation was 11.0 months. MS Contin was given on average for 1.5 months. The median survival after study enrollment was 1.8 months. Of the 50 enrolled patients, three left the study in the early phase due to drug-related adverse effects. In almost all the patients the effective dose was 60 mg/day with 45 days of response duration. The required duration for dose adjustment was nine days. The most common side effects were constipation and vomiting, which were controlled with conservative care. Two patients withdrew because of intractable vomiting and one because of mental drowsiness. In conclusion, twice-a-day moderate dose oral MS Contin therapy for cancer pain offers effective pain relief with minimal, tolerable side effects in the majority of patients in Korea. PMID- 1758824 TI - Cost considerations of analgesic therapy: an analysis of the effects of dosing frequency and route of administration. AB - Using work sampling methodologies, we compared both acquisition and administration costs of equivalent daily doses of controlled-release morphine tablets and morphine sulphate solution. A total cost for each drug therapy was derived by summing: (i) the acquisition cost of the medication, (ii) the cost of drug administration supplies, (iii) the cost of pharmacy time required for packaging and distribution of doses to nursing units, (iv) the cost of nursing time required to administer the medication, (v) the cost of nursing time required to complete the requisite narcotic records. Acquisition costs for controlled release morphine tablets, morphine sulphate solution and ancillary materials required for dosing were those actually paid by the hospital pharmacy at the time of the study. Costs for nursing and pharmacy time for administration of doses were based on our analysis of the time required to perform each step of the procedure and the median hourly wage for the corresponding position from the British Columbia collective agreement. Assuming a mean total daily morphine dose of 120 mg, administered as one 60 mg controlled-release morphine tablet 12 hourly or 20 mg (4 ml of 5 mg/ml) morphine sulphate solution 4 hourly, morphine solution had a lower acquisition cost than controlled-release tablets ($0.48 vs. $2.32 per day; respectively). However, the saving in acquisition costs was offset by a higher administration cost ($10.20 vs. $2.86 per day). These figures indicate that administration of 120 mg morphine per day to hospitalized patients for 30 days would have a total cost of $155.40 using a regimen to 60 mg controlled release morphine 12 hourly. In contrast, total cost for a 30 day regimen of 20 mg morphine solution 4 hourly would be $320.40. Thus, an analysis which considers both acquisition and administration costs reveals that the frequency of administration is an important factor in the overall cost of drug therapy and that controlled-release formulations may ultimately be less costly to administer than their immediate release counterparts. A separate analysis of costs associated with the administration of morphine by continuous subcutaneous infusion demonstrated that providing analgesia by this route was significantly more costly than via the oral route. PMID- 1758825 TI - Guidelines for the use of MS Contin tablets in the management of cancer pain. AB - MS Contin (controlled-release oral morphine) has been successfully used to treat moderate to severe pain associated with cancer. The indication for administering MS Contin is not a poor prognosis, but rather pain requiring repeated dosing with potent opioids over periods of more than a few days. Individualization of analgesic dosage to each patient's needs can provide excellent relief of pain in most patients but require selection of the right analgesic in the right dose at the right intervals. PMID- 1758826 TI - AIDS and cancer pain treated with slow release morphine. AB - The use of slow release morphine was compared between those with cancer and those with advanced HIV disease in two retrospective studies covering a total of 512 patients at home. Pain was found to be less severe in HIV/AIDS but still requiring opioid use in over a third of patients of which 14% needed subcutaneous diamorphine infusion when seriously ill at home. Slow release morphine was used by 45% of those with cancer and 17% of those with HIV/AIDS. It was found to be a simple and convenient preparation for use at home with most patients never needing more than 30 mg twice daily. Half the cancer patients prescribed slow release morphine were able to take it until the day of death. PMID- 1758827 TI - Hospice care in Japan. AB - In 1990 hospice care services in Japan entered a new era when the national government authorized medical insurance coverage for hospice care. Within the last decade in Japan, gradual yet remarkable progress has taken place in a perception of the need for hospice care services. It was in 1981 that the first hospice opened in Japan, followed by five other hospices in a 9 year period. These have been well received both by public and medical professionals, although many difficulties have been encountered in establishing them. It is hoped that further development will include an increase in the number of hospices, a growing awareness within general hospitals of hospice style approach to care, and additionally, an expansion in home care services. PMID- 1758828 TI - Angina clinical trial methodology. AB - This paper reviews the general structure of clinical trials with special reference to those in the area of angina. In particular, aspects of experimental design in exercise testing, ambulatory monitoring and mortality studies are examined critically. Parallel group and crossover studies are compared and contrasted. Sensitivity analysis of the power of any proposed trial is recommended, and problems that can arise in the area of event rate estimation are illustrated. Additional problems associated with trials involving combination therapies, trials with no placebo group and regression to the mean are discussed. PMID- 1758829 TI - Progression and regression of atheroma. AB - Normal human arteries accumulate lipid in the intima with increasing age. These lipids are laid down in proportion to their distribution in low-density lipoprotein, suggesting that they are derived from this source. With their accretion, the amount of cholesterol and its esters in the subintimal space increases significantly, leading to the development of insoluble crystals which are difficult to remove by any therapeutic intervention. It has been shown that treatment with a low-cholesterol diet combined with lipid-lowering drug treatment can halt progression of atherosclerotic lesions, but as yet ther is no conclusive evidence that consistent lesion regression is possible. PMID- 1758830 TI - Circadian rhythms in cardiovascular function. AB - This short overview discusses circadian rhythms observed in cardiovascular events such as myocardial ischaemia and myocardial infarction, which occur most frequently in the morning. Changes in the frequency of occurrence seem to be related to, and may result from, circadian rhythms in factors such as heart rate, blood pressure, coronary artery tone, platelet adhesiveness and blood fibrinolytic activity, which could be involved in triggering myocardial ischaemia or infarction. Consideration of the circadian rhythm of myocardial ischaemia and serious cardiovascular events may be important when medical therapy is selected. PMID- 1758831 TI - Nocturnal asthma: mechanisms and the role of theophylline in treatment. AB - Asthma is characterized by airway inflammation and hyper-responsiveness. Clinically, these features are manifested by attacks of cough, wheezing, and dyspnoea. Nocturnal asthma symptoms are frequent; 39% of asthmatics awaken nightly, and 94% have nocturnal awakenings at least once a month. A number of mechanisms have been hypothesized to explain the phenomenon of nocturnal asthma, including exposure to dust mite allergen, late-phase allergic reactions, effects of posture and sleep stage on airway tone, gastro-oesophageal reflex, impaired mucociliary clearance, airway cooling, and changes in circadian rhythms of circulating hormones. While no single mechanism can explain these changes, circadian rhythms may be particularly relevant. Normal airway tone increases during sleep and is magnified in asthmatics. Bronchial responsiveness to histamine and allergen challenge increases during sleep and mast cell mediator release is enhanced. Circulating eosinophils increase, which may allow their ingress into pulmonary tissue. Decreases in plasma catecholamine and cortisol levels have also been observed. All of these may influence airway tone, inflammation, and responsiveness during sleep and produce the observed clinical picture. Inhaled sympathomimetics are frequently ineffective in preventing nocturnal symptoms due to their short duration of action. While corticosteroids, cromoglycate, and anticholinergics are effective, sustained-release theophylline is particularly advantageous for controlling nocturnal symptoms. Once-daily theophylline when dosed in the evening not only controls nocturnal symptoms and improves airflow during the early morning hours, but decreases airway responsiveness to histamine as well. The close association between airway inflammation, airway hyper-responsiveness, and nocturnal asthma symptoms makes further studies of the mechanism of action of theophylline especially interesting. PMID- 1758832 TI - Role of theophyllines in severe chronic obstructive pulmonary disease. AB - Theophyllines are effective bronchodilators, but have other respiratory effects which may be beneficial in patients with chronic obstructive pulmonary disease. These effects include increased diaphragmatic contractility, central respiratory stimulation and anti-inflammatory actions. Some controversy exists however on the precise role of these effects in the clinical setting. We examined the effects of a long-acting theophylline preparation (Uniphyllin Continus) on pulmonary function, and on ventilation and gas exchange during rest, sleep and exercise in a group of 12 patients with severe (FEV1 32 +/- 8.3% predicted), but stable chronic obstructive pulmonary disease. The study was randomised, placebo controlled, and double-blind in nature. Preliminary analysis of the data indicates a significant improvement in the degree of hyperinflation and gas trapping with theophylline, and oxygen levels were improved during rest, sleep and exercise while on theophylline. These findings confirm a beneficial effect of theophylline in such patients. PMID- 1758833 TI - What use is steady-state theophylline in severe chronic obstructive pulmonary disease? A preliminary report. PMID- 1758834 TI - [Therapy of severely mentally-retarded patients with depressive symptoms in long term inpatient facilities]. AB - Early childhood communication and interaction often can be found in the severely mentally retarded. Adequate responding to this kind of behaviour plays a crucial role in the therapy of symptoms of depression. PMID- 1758835 TI - [Stress and coping with stress by mothers of children with mild cerebral dysfunctions]. AB - Adapting the paradigm developed by Richard Lazarus, parenting stress and coping were studied among mothers of children (n = 42) with Minimal Brain Dysfunction (MBD) and mothers with non-disabled children (n = 42), aged 6 to 9. The children of control mothers were matched by age, sex, social status, and maternal marital status with the MBD children. The mothers of MBD children were found to experience more parenting difficulties, more negatively toned cognitive appraisals of their stakes in parenting and less positive adaptational outcomes than their controls. The mothers of MBD children appraised their mastery lower than their controls. However, family well-being, or self-esteem did not differ between the mothers of MBD children and their controls. PMID- 1758836 TI - [Report on the International Congress of Child and Adolescent Psychiatry in Bad Homburg]. PMID- 1758837 TI - Cigarette smoking in the Multiple Risk Factor Intervention Trial (MRFIT). Introduction, overview, method, and conclusions. PMID- 1758838 TI - Comparison of smoking behavior change for SI and UC study groups. MRFIT Research Group. AB - BACKGROUND: The results of MRFIT smoking intervention program are presented for the 4,103 special intervention and 4,091 usual care men who reported smoking cigarettes at the first screening visit. RESULTS: Among the special intervention men, the reported cessation rate increased from 43.1% at 12 months to 48.9% at 72 months. The reported cessation rate among the usual care men increased from 13.5% at 12 months to 28.8% at 72 months. Among smokers who reported cessation at 72 months, 51.3% of special intervention men and 22.7% of usual care men had quit smoking within the first year and remained abstinent thereafter. Average thiocyanate and expired-air carbon monoxide served as objective measures of smoking and were significantly lower among the special intervention men than among the usual care men over the entire follow-up period. The reported cessation rates at 72 months varied according to initial levels of smoking. Smokers reporting 1-19 cigarettes per day at entry were more likely to quit than heavier smokers. For each category of smoking at entry (1-19, 20-39, and 40 or more cigarettes per day) significantly more special intervention than usual care smokers reported cessation. CONCLUSION: These results indicate that the MRFIT smoking intervention program was successful in promoting early cigarette smoking cessation and maintaining cessation over the entire trial for a large percentage of cigarette smokers. PMID- 1758839 TI - Evaluation of two biological markers of tobacco exposure. MRFIT Research Group. AB - This study assesses serum thiocyanate and expired-air carbon monoxide based on findings for 8,895 participants in the Multiple Risk Factor Intervention Trial. For each marker and combination of markers, a logistic probability model was used to generate a plot of true positive vs false positive rates (an operating characteristic curve), an optimal cutpoint, and the positive predictive value for discriminating tobacco smokers (cigarettes, pipes, cigars, or cigarillos) from non-tobacco smokers. Optimal cutpoints were 83 mumols/liter for thiocyanate and 10 ppm for carbon monoxide. These cutpoints were applied to the entire group to evaluate accuracy. Specificity was higher for carbon monoxide than for thiocyanate (91.8 vs 87.3%) and sensitivity was lower (85.7% for carbon monoxide vs 88.8% for thiocyanate). When carbon monoxide and thiocyanate were both used, specificity was 92.7% and sensitivity was 89.1%. The estimated cutpoints derived from the Multiple Risk Factor Intervention Trial result in predictive values greater than 87% when the prevalence of smokers is greater than 50%. Cutpoints should be modified to maximize the predictive value when the prevalence of smokers is less than 50%. Both serum thiocyanate and carbon monoxide are good markers of smoking exposure. Serum thiocyanate may be preferable to carbon monoxide because of its longer half-life. PMID- 1758840 TI - Baseline factors associated with smoking cessation and relapse. MRFIT Research Group. AB - BACKGROUND: Data on smoking cessation and relapse for 6 yers of the Multiple Risk Factor Intervention Trial were evaluated in univariate and multivariate analyses to determine the relationship between variables measured at the beginning of the trial and smoking cessation and relapse for special intervention and usual care participants. RESULTS: The variables positively associated with smoking cessation in both the SI and the UC groups included age, education, and past success in quitting; there was a negative association with the number of cigarettes smoked per day. The expectation of quitting was positively associated with cessation in the special intervention group only, while life events, alcohol, and the presence of a wife who smokes were significant predictors of reduced cessation for the usual care group. The special intervention program may have overcome obstacles which interfered with cessation among the usual care participants. Associations with relapse were generally stronger in the usual care group than in the special intervention group. For usual care participants, multivariate analyses showed that education, past success in quitting smoking, alcohol, and life events were associated with relapse rates. For special intervention participants, only alcohol emerged as a significant predictor. Conclusion. The data are relevant in terms of factors that govern smoking cessation and relapse for adult smokers who take part in formal intervention programs and for those who are left to modify their behavior on their own. PMID- 1758841 TI - Smoking cessation and change in diastolic blood pressure, body weight, and plasma lipids. MRFIT Research Group. AB - Cigarette smoking cessation was examined for its impact on diastolic blood pressure, weight, and plasma lipids in 3,470 special intervention males in the Multiple Risk Factor Intervention Trial. Change in smoking status (quitters vs nonquitters) was not independently associated with change in diastolic blood pressure or the subsequent use of antihypertensive medication for smokers who were normotensive at entry. More quitters (35%) became hypertensive than nonquitters (27%, P less than 0.01), although the groups had similar baseline diastolic blood pressure levels. Weight gain subsequent to cessation probably contributed to this excess incidence of hypertension in quitters. Stepped-care antihypertensive therapy lowered diastolic blood pressure similarly for hypertensive quitters and nonquitters. Weight increases of 6 lb or more by the 72 month visit occurred in 47% of quitters vs 25% of nonquitters (P less than 0.01); quitters did not differ from nonquitters in their change in total kilocalories from baseline to the 72-month visit. Quitters who gained 6 lb or more tended to be less obese at baseline, be less physically active, and smoke more cigarettes per day than those who did not gain this amount. Finally, quitters relative to nonquitters experienced an adjusted increase of 2.4 mg/dl high-density lipoprotein cholesterol, but no difference in total or low-density lipoprotein cholesterol. The implications for intervention are discussed as they relate to the common, but not inevitable, increase in weight subsequent to cessation. PMID- 1758842 TI - Pulmonary function in relation to cigarette smoking and smoking cessation. MRFIT Research Group. AB - BACKGROUND: More than half of the subjects in the MRFIT smoked at baseline and 10% of the subjects stopped smoking permanently during the first year of the trial. In this report, rates of decline in forced expiratory volume in 1 sec (FEV1) are compared for early permanent quitters and smokers who continued to smoke throughout the trial. METHODS: Since pulmonary function testing was not standardized across all centers until the third annual visit cycle, change in FEV1 is examined over the latter half of the trial; the level of FEV1 is analyzed cross-sectionally at the midpoint of the trial. Analyses are limited to 4,926 subjects who never used beta-blockers or smoked cigars, cigarillos, or pipes during the trial and who had annual FEV1s measured over 2-4 years in the latter half of the trial. RESULTS: Quitters during the first 12 months experienced smaller declines in FEV1 over the latter half of the trial than continuing smokers, with -50.7 ml/year versus -59.0 ml/year, respectively, adjusted for the level of FEV1 (P = 0.05). Cross-sectionally, those who had never smoked, former smokers, quitters, and continuing smokers showed a gradient of decreasing FEV1, and all four smoking groups were significantly different from each other (P less than 0.05). CONCLUSIONS: These data suggest that if a middle-aged, healthy smoker stopped smoking permanently, he could expect his FEV1 to deteriorate at a more gradual rate 3-4 years after stopping smoking than a similar smoker who continued to smoke. No information was available for the complete MRFIT cohort on the pulmonary function effects immediately following smoking cessation. PMID- 1758843 TI - Cigarette smoking and mortality. MRFIT Research Group. AB - METHODS: The relationship of cigarette smoking and smoking cessation to mortality was investigated among men screened for and also among those randomized to the Multiple Risk Factor Intervention Trial (MRFIT). RESULTS: Among the 361,662 men screened for the MRFIT, cigarette smoking was an important risk factor for all cause, coronary heart disease (CHD), stroke, and cancer mortality. These risks, on the log relative scale, were strongest for cancers of the lung, mouth, and larynx. The excess risk associated with cigarette smoking was greatest for death from CHD. Overall, approximately one-half of all deaths were associated with cigarette smoking. Among the 12,866 randomized participants, weak positive associations with duration of cigarette smoking habit and tar and nicotine levels were found with all-cause mortality. For both SI and UC men, substantial differences in subsequent CHD (34-49%) and all-cause (35-47%) mortality were evident for men who reported cigarette smoking cessation by the end of the trial compared with those continuing to smoke. There was no evidence that lung cancer death rates were lower among cigarette smokers who quite compared with those who continued to smoke in this 10-year follow-up period. CONCLUSION: The data are consistent with results of previous epidemiologic studies indicating that the benefits of smoking cessation on CHD are rapid, while for lung cancer, the benefit is not evident in a 10-year follow-up period. PMID- 1758844 TI - Association between baseline risk factors, cigarette smoking, and CHD mortality after 10.5 years. MRFIT Research Group. AB - METHODS: The association between baseline risk factors and death from coronary heart disease (CHD) after 10.5 years was investigated for cigarette smokers and nonsmokers who entered the Multiple Risk Factor Intervention Trial (MRFIT). RESULTS: Rates per thousand person-years of CHD mortality were higher for smokers than for nonsmokers at every level of baseline risk factors examined. There were significant associations between CHD mortality and plasma low-density lipoprotein and high-density lipoprotein cholesterol for smokers and nonsmokers. The inverse association between CHD mortality and high-density lipoprotein cholesterol was significantly stronger among nonsmokers compared with that among smokers and was attributable to a very strong association for former smokers. An inverse relationship between CHD and body mass index was evident for smokers and nonsmokers. Rates of CHD death rose sharply when levels of fasting glucose exceeded 140 mg/dl, and there was a significant association between CHD mortality and blood sugar levels for nonsmokers but not for smokers. For both smokers and nonsmokers, an inverse univariate association between alcohol consumption and CHD mortality was evident. This association, however, did not persist after adjustment for plasma high-density lipoprotein cholesterol. CONCLUSION: Intervention on blood pressure and blood lipids is particularly important among cigarette smokers because of their increased risk of CHD death. The different associations between high-density lipoprotein cholesterol, fasting serum glucose, and CHD mortality for smokers and nonsmokers requires further investigation. PMID- 1758845 TI - [The history of tuberculin therapy--its discovery by Robert Koch, its forerunners and further development]. AB - Since tuberculosis had not been known either in its nature or in its proper therapeutics for thousands of years, Robert Koch (1843-1910) 1882 discovered its germs and 1890 recommended its treatment with tuberculin, i.e. an extract of its bacterial cultures. During the "Tuberkulin-sturm" which ensued from the publication of Koch, the substance was at once proved in numerous clinics in many countries. But in spite of sophisticated procedures of production it could not become standard therapy because of its considerable side-effects when not being applied accurately. In selected cases therapy with tuberculin is still applied even today. However, the effort of treating tuberculosis with tuberculin had already been made before its propagation by Robert Koch. Yet the forerunners of Koch's therapy with tuberculin had not been recognized by scientific medicine at the time because of lacking plausibility of its fundamental principles--not before Emil von Behring (1854-1917) within his scientific researches came to an explicit recognition of the homeo- and isopathetic principle of treatment. PMID- 1758846 TI - [Bronchoalveolar lavage in fibrosing alveolitis--a parameter for evaluating activity and prognosis?]. AB - Bronchoalveolar lavages (BAL) were performed in 19 patients in whom fibrotising alveolitis had been detected and confirmed. The patients were then followed up and controlled clinically for more than 12 months. The courses of the diseases did not reveal any group-specific behaviour (taking lymphocytic and granulocytic lavages into consideration) and were not predictable on the basis of the lavage patterns. With a BAL lymphocytosis, 40% of the patients showed clinical improvement and in 30% the disease became stable whereas in another 30% there was a deterioration. If more than 10% BAL granulocytes were present, 50% of the patients showed clinical deterioration, whereas the course became stable in 37.5% and clinical improvements were recorded in 12.5% of the patients. PMID- 1758847 TI - [Aspects of mucociliary clearance in mucoviscidosis]. AB - Very often the respiratory tract of patients suffering from mucoviscidosis is infested with Pseudomonas aeruginosa which is accused of forming substances that inhibit ciliary motility. It is the aim of the present study to examine the influence of an acute and clinically relevant pseudomonas infestation on the ciliary beat frequency. The ciliary beat rate was determined in 25 mucoviscidosis patients, 13 of them were hospitalised because of acute bronchopulmonary infections. 12 of the patients did not show any clinical signs of an acute respiratory tract infection. In the group of the 13 hospitalised patients, 10 patients (77%) showed infestation of the respiratory tract with Pseudomonas aeruginosa, the mean ciliary beat frequency being markedly reduced at 8.2 +/- 1.7 Hz compared to that of a healthy group with 9.9 +/- 1.0 Hz. The 12 outpatients without clinical signs of acute respiratory tract infections did not show any reduction of the ciliary beat frequency (9.9 +/- 1.4 Hz). Basing on these results, determination of the ciliary beat frequency may possibly develop into an auxiliary criterion to decide on starting a Pseudomonas-active antibiotic therapy. PMID- 1758848 TI - [Effects of the PAF antagonist WEB 2086 on hypoxia and angiotensin II-induced pulmonary vasoconstriction in the isolated perfused rat lung]. AB - Using isolated blood-perfused lung preparations of rats, we tested the influence of the PAF antagonist WEB 2086 on vasoconstriction triggered by hypoxia or angiotensin II (A II). If a constant flow was pre-set, changes in the prepulmonarily measured pressure were directly related to the changes of resistance in the pulmonary flow. WEB 2086 reduced the hypoxically conditioned vasoconstriction (HPV) when using blood as perfusion medium, the effect being dependent on the dose (ED50 = 127.3 +/- 21.1 mg/l). HPV was lowered on the average by 82% if the full pharmacologic dose of 800 mg/l WEB 2086 was added to the perfusate. The A II response was weakened to a lesser degree (by 45%). If plasma was used as perfusate, the pressure increase in response to hypoxic stimulation or A II was less marked. However, the relative effect of the PAF antagonist was analogous (attenuation by 83% or 53%, respectively). In chronically hypoxic animals (3 weeks at 10% O2) the relative pressure drop in the lesser circulation after application of WEB 2086 (400 mg/l; HPV; blood as perfusate) was definitely more pronounced (p less than 0.001). The fact that WEB partly antagonises the pulmonary vasoconstriction triggered both by alveolar hypoxy and by angiotensin II, seems to indicate that in both constrictive stimuli PAF participates in the complex mediator mechanism or that WEB 2086 exercises a non-specific vasodilatory effect on the pulmonary flow. PMID- 1758849 TI - [Pearl oyster dust as the cause of exogenous allergic alveolitis]. AB - Many different inhalative substances may cause allergic alveolitis (hypersensitivity pneumonitis). We report on a worker who developed lung fibrosis due to the sensitization to pearl oyster shell dust. High concentrations of IgG antibodies to proteins (conchagens) of the shell which appear to represent the relevant antigens were found in the patient's serum. PMID- 1758850 TI - [The role of phenotypic factors in predicting the effectiveness of pharmacological prevention of tuberculosis in children]. AB - The role of genetic markers such as dermatoglyphics, sex and INH inactivation in predicting the efficiency of tuberculosis chemoprophylaxis has been studied in 76 children (41 boys and 35 girls) with a tuberculin reaction reversal. The dermatoglyphic signs and the type of INH inactivation were found to be related to the efficiency of chemoprophylaxis. This makes it possible to use the child's phenotype for prognosis and better individual approach to tuberculosis chemoprophylaxis. An association has been found between the INH inactivation type and dermatoglyphics. PMID- 1758851 TI - [Improving ambulatory services for children in the foci of tuberculosis with special reference to the factors of increased risk of infection]. AB - The paper deals with the results of the examination of certain factors that increase the risk of children's contamination in tuberculosis infection foci. It has been established that primary infection takes place more frequently in children under 6 years of age (1.3-fold), in children who do not attend preschool establishments (2-fold), in those having inappropriate BCG vaccination and revaccination (2.4-fold) and in the foci where patients abuse alcohol (2.2-fold). These children comprise a group of especially high contamination risk. It is expedient to check up them 3 times a year, performing a tuberculin test in children showing an uncertain response, to conduct clinical and X-ray examinations in accordance with the indications and to strictly controlled chemoprophylaxis. The proposed scheme of children's medical examination is one of the pattern to make better therapeutic and preventive measures in tuberculosis infection foci. PMID- 1758852 TI - [Groups with the risk of tuberculosis]. AB - A specially developed screening was used to examine 652 workers of an assembly shop of a watch plant whose work is characterized by their being in a constrained position for hours which leads of general inactivity and hypoventilation. Disturbances of external respiratory function were found in 180 (27.6%) subjects, which is associated with their working conditions rather than with smoking. These subjects deserve special care since the pre-clinical obstructive bronchial changes can be the precursors of broncho-pulmonary diseases and later of tuberculosis. PMID- 1758853 TI - [Differential diagnosis of disseminated processes in the lungs in adolescents]. AB - The paper deals with the data of follow-up of adolescents with disseminated pulmonary processes of different etiology. Among the patients who were treated in the department during the last 10 years disseminated processes amounted to 3.3%, with disseminated pulmonary tuberculosis being recorded in 1.3% and dissemination of the nontuberculous etiology in 2% of the patients. Mucoviscidosis, metastasis, of the thyroid cancer, histiocytosis X, toxoplasmosis and echinococcosis were among the disseminations of the nontuberculous etiology. Basic diagnostic criteria have been determined. PMID- 1758854 TI - [Effectiveness of using external laser irradiation in the complex treatment of patients with pulmonary tuberculosis with concomitant bronchial obstruction syndrome]. AB - External laser radiation (ELP) (18-20 daily procedures) was used together with chemotherapy in the combined treatment of 53 patients with destructive pulmonary tuberculosis characterized by delayed dynamics of the process and concurrent obstructive bronchial syndrome. ELR promoted acceleration of the process dynamics, closure of disintegration cavities and alleviation of bronchial obstruction phenomena. The mechanisms of a favourable ELR action were essentially due to the reduction of basal oxidative metabolism and enhancement of defensive reaction during contact with a specific pathogen in phagocytes, which was confirmed by the recorded results of the spontaneous and stimulated by the killed BCG culture NST rest in peripheral neutrophils and monocytes. PMID- 1758855 TI - [Effectiveness of the treatment of patients with fibrous-cavernous pulmonary tuberculosis]. AB - The follow-up of 301 patients with fibrous-cavernous pulmonary tuberculosis has demonstrated that the disease outcome and treatment effectiveness depend on the nature of its course. A long-term specific therapy for 9-10 months brings about cessation of bacillary excretion in 50-60% of cases even in a progressive course of the disease and closure of destruction cavities occurred in 12.5% of cases with rapid progression and in 21.7% of cases with slow progression of the disease. Despite all measures taken, stabilization of the process fails in one fourth of the patients with rapidly progressing fibrous-cavernous tuberculosis and in 9% of those with a slowly progressing course. In 90% of cases bacillary excretion in patients with stable fibrous-cavernous tuberculosis ceased in 3 months and in 100% after 6 months of treatment. PMID- 1758856 TI - [The hemostatic system in patients with pulmonary tuberculosis during their preparation for surgery]. AB - The basic mechanisms responsible for equilibrium impairment in the hemostatic system in pulmonary tuberculosis patients are reduced activity of antithrombin III and disturbances of platelet functional capacities. These changes were proved to reflect the course of intravascular hemocoagulation whose degree of manifestation is related directly to the extent of specific lesions in the lungs and intoxication phenomena. The process of intravascular hemocoagulation in tuberculosis patients runs in the presence of an increased concentration of plasma fibronectin , while major surgery performed in patients with fibrous cavernous processes leads to its reduced level. It is pathogenetically proved to use antithrombin III concentrate preparations with anti- and dysaggregatory properties, fibronectin preparations, trasylol or its analogs during complex preoperative preparation of patients. PMID- 1758857 TI - [Evaluation of the contractile capacity of the ureter and kidney pelvis in tuberculosis by the method of infusion dynamic uretero- scintigraphy]. AB - The radionuclide method--infusion dynamic ureteroscintigraphy--was used to examine 123 patients with tuberculosis of the urinary organs and 51 patients of the control group. Contractility parameters of various portions of the ureters and pelves in varying urinary tuberculosis were established. The contractility of the pelves and ureters was proved to be impaired even prior to the appearance of visible X-ray changes in the ureters. A specific increase in contractility in the area from the pelvis to the middle third of the ureter and further reduction in the lower third were seen. PMID- 1758858 TI - [Functional disorders of the central nervous system in patients with pulmonary tuberculosis]. AB - Two groups of pulmonary tuberculosis patients were followed up to reveal the relation between the lipid peroxidation (LPO) processes and the function of the central nervous system (CNS) in pulmonary tuberculosis. Group 1 (n = 76) included subjects with normal baseline electroencephalographic findings; group 2 (n = 41) consisted of those with profound changes in the electroencephalogram. The findings of LPO processes were assessed by the blood levels of malonic dialdehyde and alpha-tocopherol. Group 2 showed a direct relationship between the progression of neurotic symptoms and the abnormal changes in the values of LPO processes. It is concluded that it is expedient to use antioxidants in the combined treatment of pulmonary tuberculosis patients to eliminate the baseline CNS changes caused by the specific process. PMID- 1758859 TI - [Problem of cutaneous tuberculosis]. AB - Case histories of 97 patients were analysed to study the diagnosis, differential diagnosis and incidence of recurrences of tuberculosis of the skin. A combined examination revealed Basin erythema in 57.7% of the patients, lupus vulgaris in 29.9% and papulonecrotic tuberculosis of the skin in 12.4%. Recurrences were recorded in 15.4% of the cases. Our study gives evidence that tuberculosis of the skin is diagnosed from the combined examination of the patient in which histologic study of a skin biopsy specimen is most essential. The differential diagnosis of tuberculosis of the skin makes difficult the distinction between the disseminated forms and allergic vasculitis and sarcoidosis of the skin. The relapse depends on how adequate the major and antirecurrence courses of antibacterial therapy were. PMID- 1758860 TI - [Status of the hemostatic system in patients with chronic lung diseases]. AB - Blood rheologic properties and homeostasis system were comprehensively examined in 23 patients with fibrous-cavernous pulmonary tuberculosis and 58 patients with various chronic nonspecific pulmonary diseases complicated by respiratory failure. The patients were found to have signs of erythrocyte edema, their more rapid depletion, lower resistance and higher aggregation which was accompanied by increased hematocrit and normal erythrocyte count. The thromboelastograms showed that all all phases of blood coagulation were shortened and fibrinolysis was deeply depressed. There was an increase in activated partial thromboplastin and thrombin time, a reduction in the values of the prothrombin indices and antithrombin III activity and higher heparin levels. The fibrinogen level was either normal or reduced despite an increase in other acute phase reactants, followed by the appearance of large amounts of blocked fibrinogen in the blood. Analysis of the findings enabled one to regard a combination of the above changes as signs of the latent DIC syndrome. Determination of fibrin and fibrinogen degradation products in a deep and long-term inhibition of fibrinolysis loses its diagnostic significance. PMID- 1758861 TI - [Extra-focal instrumental fixation of the spine in the surgical treatment of tuberculous spondylitis]. AB - The complex procedure for treating tuberculous spondylitis involving a short-term (1-2 months) antibacterial therapy and early functional resection of the diseased vertebral bodies with defect replacement by an autograft and extra-focal fixation of the resected spinal portion by Byzov's apparatus applied in 492 patients proved to be highly efficacious. The reliable apparatus fixation of the spinal zone operated on allows early (on day 7) activation of patients which promotes functional normalization of organs and systems, activation of reparative processes, shortening of treatment duration and reduction of disabled cases. Clinical and X-ray findings show that a bone block formed 4-6 months after surgery and 67% of the patients finished their therapy during a year. Introduction of the procedure into the treatment of spinal injuries and diseases will be of the socioeconomical value. PMID- 1758862 TI - [Tuberculosis of the endocrine system (thyroid, adrenal and pituitary glands)]. PMID- 1758863 TI - [Detection of antibodies against Mycobacterium tuberculosis in patients with lung diseases by immunoenzyme analysis]. AB - Diagnostic enzyme immunoassay kits were used for the examination of parallel tests of venous and capillary blood in 43 patients with nonspecific pulmonary diseases for the presence of antibodies to tuberculosis pathogen. The method of parallel tests has revealed that disregarding the site of blood collection (vein, finger) the EIA results are identical. Analysis sensitivity in tuberculosis patients varies within 30 and 86% in relation to the clinical activity of a tuberculosis process. Analysis specificity in tuberculosis patients is 3.4%. PMID- 1758864 TI - [Use of dimephosphon in pathogenetic therapy of experimental tuberculosis]. AB - The results of a study of a new synthetic drug dimephosphon used as a pathogenetic means in the treatment of experimental tuberculosis are presented. Dimephosphon was found to be responsible for both the in vivo and in vitro decrease of the degree of MBT resistance to rifampicin. The findings of macroscopic, histologic and bacteriologic examinations demonstrated a significant increase in the effectiveness of antituberculous therapy. Dimephosphon monotherapy in mice elicited manifested stimulation of peritoneal macrophages: increase in O2- production, and decline in extracellular 5-nucleotidase activity. Nemolysine-synthetic cellular splenic activity in mice rose essentially. No direct stimulating influence of dimephosphon on functional macrophage activity in vitro was found. PMID- 1758865 TI - [Experimental bioplasty of tuberculous caverns of the lung]. AB - A possibility of using allontransplants of the "Alloplant" series for pulmonary cavernoplasty has been developed and substantiated experimentally. Histological studies of an experimental pulmonary cavern under conditions of allotransplantation revealed the dynamics of the morphological transformation typical of human pulmonary cavern healing. A reparative process results in the liquidation of the specific changes in the cavern wall followed by the formation of a regenerate in the form of a stellate cicatrix. PMID- 1758866 TI - [Causes of recurrences of pulmonary tuberculosis]. PMID- 1758867 TI - [Extended thoracoplasty with extra-pleural embolization in patients with disseminated pulmonary tuberculosis]. PMID- 1758868 TI - [Possibilities of computerized immunodiagnosis of tuberculosis and related lung diseases]. AB - The results of a computer analysis of immunograms for the differential diagnosis of tuberculosis, cancer, pneumonia and sarcoidosis are presented. The findings indicate that computer immunodiagnosis may be used as a supplementary tool that increases the effectiveness of diagnosis in difficult cases. The advantage of the elaborated system is to rapidly apply a systemic approach to the assessment of the patient's immune status and to objective diagnosis by using computer algorithms. PMID- 1758869 TI - Comparative studies on the detection of hepatitis B virus DNA in frozen and paraffin sections by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) is an extremely sensitive technique that has been used for detection of DNA sequences in formalin-fixed, paraffin-embedded tissues. In order to verify that hepatitis B virus (HBV) DNA sequences are adequately preserved in routinely processed liver tissues, we performed PCR with five different primer pairs for HBV sequences on DNA extracted by two different methods from paraffin and frozen liver sections. The amount of PCR products obtained with DNA templates extracted by the proteinase K-SDS method from frozen sections was significantly larger than that from paraffin sections. However, boiling of deparaffinized sections in water containing Chelex-100 resulted in ample amounts of PCR products irrespective of the primers used. On Southern blots, the location of the bands of amplified DNA obtained by the different methods was consistent with the predicted size, suggesting that the viral sequences had not been altered by processing. Although freezing of fresh tissue yields quantitatively more HBV DNA, formalin fixation qualitatively preserves the viral DNA sequences adequately for detection by PCR. Therefore, formalin-fixed, paraffin-embedded tissues may be used for the detection of viral DNA sequences by PCR. Application of the described procedure to routinely processed tissues significantly broadens the applicability of this powerful diagnostic and investigative method. PMID- 1758870 TI - Immunohistochemical studies of human immunodeficiency virus-1 in liver tissues of patients with AIDS. AB - A wide spectrum of hepatic lesions has been reported in AIDS, but it is not known whether the changes are related to the presence of human immunodeficiency virus type 1 (HIV-1). Therefore, we examined liver sections from 15 consecutively autopsied patients with AIDS for the presence of HIV-1 antigens p24 (core) and gp41 (envelope) by the avidin-biotin-peroxidase complex method using monoclonal antibodies. The most common histologic abnormalities noted were steatosis, portal inflammation, Kupffer cell hyperplasia, and focal hepatocellular and bile duct damage. Intra-hepatic opportunistic organisms were detected in six of 15 (40%) cases, with Mycobacterium avium-intracellulare being the commonest (four cases). Immunoreactivity for HIV-1 antigens was demonstrated in 12 of 15 cases (80%), with staining limited to Kupffer cells and other mononuclear cells characterized by a lymphoid morphology. Approximately the same number and type of cells were stained with both monoclonal antibodies and did not bear any relation to the degree of histologic abnormalities nor to the presence of opportunistic infections. The data suggest that some pathologic changes in AIDS livers are more likely the result of an indirect effect mediated by infected resident and circulating mononuclear cells than a direct cytopathic effect of HIV-1. PMID- 1758871 TI - Immunocytochemical characterization of a monoclonal antibody directed against mitochondria reactive in paraffin-embedded sections. AB - The monoclonal antibody mES 13 was previously produced against bacterially expressed BALB ras p21 and was reported to have both membrane and cytoplasmic reactivity in formalin-fixed, paraffin-embedded tissue sections. In the current study, the cytoplasmic reactivity of mES 13 is investigated and demonstrated to be mitochondrial. Immunoelectron microscopic studies showed specific labeling of mitochondria without labeling of other organelles. In normal tissues, the antibody strongly labeled tissues known to have large amounts of mitochondria such as renal tubules, hepatocytes, and myocardium. The pattern of reactivity of tumors generally mimicked that of normal tissues, with carcinomas and melanomas usually showing stronger staining than sarcomas and lymphomas. Two granular cell tumors were negative. Among renal neoplasms, mES 13 strongly labeled renal oncocytomas and granular cell renal cell carcinomas and showed weaker staining of clear cell and chromophobe cell tumors. The mES 13 antibody should be useful in the characterization and diagnosis of tumors in which oncocytoma is in the differential diagnosis, especially when only paraffin-embedded tissue is available for study. PMID- 1758872 TI - Blood pressure and nephrosclerosis in black and white men and women aged 25 to 54. AB - Kidney samples obtained at autopsy were evaluated for nephrosclerosis by quantitatively measuring the severity of intimal fibroplasia in the interlobular arteries and counting the number of hyalinized arterioles. Most cases were obtained from the coroner and had violent causes of death; subjects with cardiovascular diseases were excluded. Blood pressures in Health Survey data were obtained from published sources. Measures of nephrosclerosis in 365 black and white men and women in age groups 25 to 34, 35 to 44, and 45 to 54 yr were examined by three-way Analysis of Variance (ANOVA). Blacks exceeded whites in fibroplasia at all ages and in both sexes; this excess was paralleled by mean blood pressure in all comparisons. White women were not different from white men in fibroplasia; black women significantly exceeded black men at all ages. Women had lower blood pressures than men when matched for age, race, and fibroplasia; the average magnitude of this difference was 5.5 mm Hg. Since women are known to have as much hypertensive disease as men after age 50 yr, it seems possible that the arterial fibroplasia seen in young women may represent progression toward the hypertensive state, even through blood pressure does not reveal the equality of the sexes in this respect until after menopause. Hence, in women arterial fibroplasia is seen to precede a later rise in blood pressure. Arteriolar hyalinization was greater in men than in women but did not differ significantly between races. Hyalinization did not consistently follow blood pressure in comparisons between subgroups of subjects. PMID- 1758873 TI - Transthyretin immunoreactivity in choroid plexus neoplasms and brain metastases. AB - Although choroid plexus papillomas (CPP) and primary choroid plexus carcinomas (CPC) are rare neoplasms of the central nervous system, they have been the subject of a number of immunohistochemical studies. To date, no unique or specific marker for these neoplasms has been found, however. Normal choroid plexus is a major site of transthyretin (TTR) synthesis, and recently this protein has been proposed as a possible specific marker of choroid plexus differentiation in tumors. In this study, we performed immunohistochemistry for TTR on 13 choroid plexus tumors (six CPP and seven CPC) and on 23 carcinomas metastatic to the brain, four of which had a papillary architecture. We also included four ovarian teratomas that contained choroid plexus elements. Two of the CPP had diffuse staining for TTR, while the four others stained only focally. Five of the CPC stained only focally and less intensely than the control, while one case was negative. Only one CPC stained as strongly and diffusely as normal choroid plexus. Two of the papillary and six of the nonpapillary metastases had focal staining similar to that seen in the five focally positive CPC. The choroid plexus elements of the ovarian teratomas stained as strongly as the positive control. These findings indicate that TTR immunoreactivity is not restricted to primary choroid plexus tumors. Furthermore, most choroid plexus carcinomas stain only weakly or not at all. This limits the usefulness of TTR immunohistochemistry in the diagnosis of primary choroid plexus neoplasms and in the distinction of CPC from metastatic carcinoma. PMID- 1758874 TI - Morphometry and the differential diagnosis between peripheral neuroepithelioma and neuroblastoma. AB - The differential diagnosis based on morphology between neuroblastoma (NB) and peripheral neuroepithelioma (PN) is difficult, since these tumors share many architectural and cytological features. In this study, a morphometrical approach to this diagnosis is made by using nuclear (shape factors) and tissue (volume density of nuclei and stroma) parameters. Quantitative morphological analysis adds important information, which when used with clinical and biochemical data facilitates the distinction. In the majority of cases, nuclei of PN are significantly less round than those of NB and their profile is much more irregular. The density of neoplastic nuclei is significantly higher in PN. However, in a certain number of cases, even the morphometrical study confirms how difficult it may be to differentiate these two neoplastic entities, since the values of parameters are largely overlapping. This suggests the existence of a "continuum" of changing features between NB and PN, which may substantiate the hypothesis of a common histogenesis. PMID- 1758875 TI - Reliability of 3H-thymidine labeling index: cell proliferation of colorectal carcinoma in three different centers. AB - Although the 3H-thymidine labeling index (TLI) has been used extensively as a biologic marker of increased susceptibility to neoplasms or as a prognostic indicator of the clinical outcome in cancer patients, there is still some concern regarding its accuracy and reliability as a marker of cell replication. A study on the prognostic value of TLI in colorectal cancer gave us the ability to evaluate how such a measurement may vary in different laboratories. A total of 150 malignant tumors of the large bowel were studied in the period from 1988 to 1989. Microautoradiography was carried out in tumor fragments taken at surgery. There were only slight differences among the three centers involved in the investigation, mainly as regards the culture medium, exposure time, and the addition of O2 + CO2 during the incubation. No significant difference was observed among TLI values recorded in the three centers (18.3 +/- 0.9; 17.4 +/- 0.9; 15.7 +/- 1.0 mean +/- SE), and the ranges of values were almost identical. Similarly, the numbers of total and of labeled cells counted for each patient were comparable among the three centers. The frequency distribution of TLI showed a peak value between 10 and 19.9% in all three centers. Moreover, more than 80% of the observed values were within the range of 10 to 29.9%. In addition, the neoplastic areas with the highest proliferative activity ("high" TLI) showed a frequency distribution once again rather similar among the three centers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758876 TI - Endocervical involvement by endometrial carcinoma on fractional curettage: a clinicopathological study of 37 cases. AB - This is a retrospective study of 37 patients with endometrial carcinoma and presence of tumor on endocervical curettage (clinical Stage II). We intended to correlate the presence or absence of endocervical stromal invasion with the clinical behavior and other prognostic factors. Based on the endocervical curettage, three categories (CAT) were defined: CAT I: tumor fragments only (seven cases); CAT II: endocervical tissue and free-floating tumor fragments (13 cases); and CAT III: endocervical tissue and tumor with evidence of stromal invasion (17 cases). Five tumors were partly of clear cell and/or papillary serous types and three of them belonged to CAT I. Six of seven tumors with a nuclear Grade 3 were in CAT III (p less than 0.05). Nine patients had local recurrence, metastases, or died of their disease (median follow-up: 56 mo) and seven of them were in the CAT III (p less than 0.05). We conclude that despite the presence of tumor on the endocervical curettage, the lack of endocervical tissue invasion is associated with a lower nuclear grade and a less aggressive behavior. These tumors should be regarded and treated as Stage I disease. Special attention must be paid to staging of clear cell and papillary serous adenocarcinomas because of the tendency for these tumors to contaminate the endocervical curettage. PMID- 1758877 TI - Immunohistochemical and ultrastructural spectrum of hepatic sarcomas of childhood: evidence for a common histogenesis. AB - Hepatic sarcomas of childhood, which appear heterogeneous by standard morphologic criteria, pose challenging diagnostic and nosologic problems to the pediatric surgical pathologist. To identify features of these tumors that might help to clarify their origin and histologic classification, we studied 13 undifferentiated (embryonal) sarcomas of the liver (UESL) and two intrinsic hepatic rhabdomyosarcomas (RMS) using immunohistochemical and electron microscopic techniques. Immunohistochemical staining was performed on 14 tumors with use of commercially available antibodies against a variety of markers, as well as peanut agglutinin lectin; electron microscopy was performed on five UESL and both RMS. Desmin was expressed by 6/12 UESL and 2/2 RMS, muscle-specific actin by 5/12 UESL and 2/2 RMS, neuron-specific enolase by 1/12 UESL and 1/2 RMS, alpha-1-antitrypsin by 8/12 UESL and 1/2 RMS, and alpha-1-antichymotrypsin by 10/12 UESL and 1/2 RMS. Cytokeratin expression was observed in only four UESL. The overlap of immunohistochemical staining patterns and ultrastructural features shown by these obstensibly different tumors suggests a common histogenesis, perhaps from a multipotential mesenchymal stem cell. PMID- 1758878 TI - Immunocytochemical detection of p53 in human gliomas. AB - Since previous published studies of astrocytomas have shown alterations in the short arm of chromosome 17, and this chromosomal location is that which encodes the p53 protein, we used a monoclonal antibody and immunocytochemistry to detect this protein in a series of brain biopsies. The normal p53 protein has a short half-life and is not detectable using this method. Expression of an altered p53 protein was detected in 29 of 71 brain biopsies, but only in those that showed astrocytic features. p53 expression was detected in 20/32 glioblastomas, 5/12 anaplastic astrocytomas, and 3/5 mixed anaplastic oligo-astrocytomas, but only in astrocytic cells. It could not be detected in any other histologic types of primary brain neoplasms, either benign or malignant. The protein was detected in only 1/11 biopsies interpreted as showing gliosis, but this was in a patient who had previously had a resection for glioblastoma, and may have represented unrecognized infiltrating astrocytoma cells. The p53 protein was also expressed in the nuclei of the two human astrocytoma cell lines examined, U251MG and D54MG. These results are in general agreement with previous detailed chromosomal analyses that have found loss of heterozygosity in up to 60% of malignant astrocytic gliomas. PMID- 1758879 TI - In memoriam--Cyrus Levinthal. PMID- 1758880 TI - FASTRUN: a special purpose, hardwired computer for molecular simulation. AB - We describe the design, construction, and performance of a special purpose, hardwired accelerator for molecular mechanical calculations called FASTRUN. The processor was designed at Columbia University in 1984, constructed in the Instrumentation Division of Brookhaven National Laboratory, and delivered to Columbia in final form in 1989. It was rendered functional for molecular mechanics in early 1990. Together with its host Star array processor, FASTRUN has a measured performance for molecular dynamics simulations which compares favorably with present day supercomputers. The hardware replication cost of FASTRUN is on the order of $100,000.00. PMID- 1758881 TI - Changes in the electron density of the cofactor NADPH on binding to E. coli dihydrofolate reductase. AB - Quantum-mechanical electron density calculations reveal that a significant polarization is induced in the cofactor NADPH (reduced nicotinamide adenine dinucleotide phosphate) on binding to the enzyme dihydrofolate reductase. The calculations indicate that electron density corresponding to approximately 0.7 electron charges is shifted within the molecule, extending over more than 20 A. Further calculations on proposed enzyme mutants show that the polarization of NADPH on binding to DHFR is, in large part, induced by a motif of three positively charged residues. This motif was also identified to be directly responsible for the positive electrostatic potential surrounding the cofactor binding site in the enzyme. The possibility of this long-range polarization of NADPH was originally proposed based on a previous study of ligand binding to DHFR where a conserved structural motif of three positively charged residues was found to play a major role in polarizing the substrate folate over its entire length of 18 A. PMID- 1758882 TI - Protein-protein recognition analyzed by docking simulation. AB - Antibody-lysozyme and protease-inhibitor complexes are reconstituted by docking lysozyme as a rigid body onto the combining site of the antibodies and the inhibitors onto the active site of the proteases. Simplified protein models with one sphere per residue are subjected to simulated annealing using a crude energy function where the attractive component is proportional to the interface area. The procedure finds clusters of orientations in which a steric fit between the two protein components is achieved over a large contact surface. With five out of six complexes, the native structure of the complexes determined by X-ray crystallography is among those retained. Docked complexes are then subjected to conformational energy refinement with full atomic detail. With Fab HyHEL 5 and lysozyme, a native-like complex has the lowest refined energy. It can also be retrieved when starting with the X-ray structure of free lysozyme. However, some non-native complexes cannot be rejected: they form large interfaces, have a large number of H-bonds, and few unpaired polar groups. While these are necessary features of protein-protein recognition, they are not sufficient in determining specificity. PMID- 1758883 TI - Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. AB - We demonstrate in this work that the surface tension, water-organic solvent, transfer-free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well-known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25 degrees C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces. PMID- 1758884 TI - Information-theoretical entropy as a measure of sequence variability. AB - We propose the use of the information-theoretical entrophy, S = -sigman pi log2 pi, as a measure of variability at a given position in a set of aligned sequences. pi stands for the fraction of times the i-th type appears at a position. For protein sequences, the sum has up to 20 terms, for nucleotide sequences, up to 4 terms, and for codon sequences, up to 61 terms. We compare S and Vs, a related measure, in detail with Vk, the traditional measure of immunoglobulin sequence variability, both in the abstract and as applied to the immunoglobulins. We conclude that S has desirable mathematical properties that Vk lacks and has intuitive and statistical meanings that accord well with the notion of variability. We find that Vk and the S-based measures are highly correlated for the immunoglobulins. We show by analysis of sequence data and by means of a mathematical model that this correlation is due to a strong tendency for the frequency of occurrence of amino acid types at a given position to be log-linear. It is not known whether the immunoglobulins are typical or atypical of protein families in this regard, nor is the origin of the observed rank-frequency distribution obvious, although we discuss several possible etiologies. PMID- 1758885 TI - Computer design of bioactive molecules: a method for receptor-based de novo ligand design. AB - The design of molecules to bind specifically to protein receptors has long been a goal of computer-assisted molecular design. Given detailed structural knowledge of the target receptor, it should be possible to construct a model of a potential ligand, by algorithmic connection of small molecular fragments, that will exhibit the desired structural and electrostatic complementarity with the receptor. However, progress in this area of receptor-based, de novo ligand design has been hampered by the complexity of the construction process, in which potentially huge numbers of structures must be considered. By limiting the scope of the structure space examined to one particular class of ligands--namely, peptides and peptide like compounds--the problem complexity has been reduced to the point that successful, de novo design is now possible. The methodology presented employs a large template set of amino acid conformations which are iteratively pieced together in a model of the target receptor. Each stage of ligand growth is evaluated according to a molecular mechanics-based energy function, which considers van der Waals and coulombic interactions, internal strain energy of the lengthening ligand, and desolvation of both ligand and receptor. The search space is managed by use of a data tree which is kept under control by pruning according to the energy evaluation. Ligands grown by this procedure are subjected to follow up evaluation in which an approximate binding enthalpy is determined. This methodology has proven useful as a precise model-builder and has also shown the ability to design bioactive ligands. PMID- 1758886 TI - Review on crystal polymorphism of substances in the European pharmacopoeia. AB - Substances in the European Pharmacopoeia, reported as having polymorphism are reviewed. For these substances the analyst may expect irregular melting behaviour and IR spectra. PMID- 1758887 TI - Optimization of doxorubicine incorporation and of the yield of polybutylcyanacrylate nanoparticles. AB - The preparation from w/o microemulsion of polybutylcianacrylate nanocapsules incorporating doxorubicine was optimized applying a multivariate experimental design. Different variables were investigated; the responses were polymer yield, concentration of the drug in the particles and percentage of the drug incorporated. A preliminary study was carried out with the strategy of fractional factorial design; the following step was a central composite design in order to study the most important causal variables. The information collected were treated by the response surface method (REGFAC package). The optimization allowed to maximize the responses; an incorporation of about 10% of doxorubicine and a yield of about 95% were obtained, starting from values notably lower of both incorporation and yield. PMID- 1758888 TI - Fluor determination in toothpaste-extracts with fluoride-selectrode based on the kinetics of hydrolysis of sodiummonofluorophosphate. AB - The Sodiummonofluorophosphate is used in a large number of toothpastes, s, while clinical research proved that application of fluoride has an important contribution in caries prevention. This prevention is almost due to the reconstitution of the by acids disappeared hydroxylapatite Ca10 (PO4)6 (OH)2 in the toothsurface, which process goes two to three times faster in the presence of F- by sedimentation of hydroxyfluorapatite Ca10 (PO4)6 (OH)2-xFx, with a higher chemical resistance for acids. Therefore, the F- must been released from the FPO3 - during the application of the pasta, e.g. by hydrolysis in the mouth. Solutions of Na2FPO3 seem to release an important amount of free F- ions, without addition of acid, and as a function of concentration, time and temperature. The hydrolysis of FPO3-- is pH-dependent and can be studied as a pseudo-first-order reaction. The dependence of the pH is found in the kinetic expression: -dC/dt = k. [H2PO3F] [H+] = k1.C, where C is the total formal concentration of all monofluorophosphate species at time t. The Arrhenius energy of activation is 16.42 +/- 0.1 Kcal/mole. The hydrolysis of monofluorophosphoric acid has already been studied before. In the present work additional F(-)-determinations are performed with a specific F( )-selectrode, without any interference of the monofluorophosphate species, which was warned for by other authors. More recent investigation showed that in samples of controlled ionic strength little interference occurs, and phosphates in particular do not interfere. Fresh prepared solutions of Na2FPO3 were used at different pH and different temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758889 TI - Comparative microbial contamination levels in wet granulation and direct compression methods of tablet production. AB - Raw materials used for tablet production were assessed for their microbiological quality. Tablets were produced by wet granulation and direct compression methods and assessed for compliance with B.P. specifications. Samples from the production stages in the two tabletting processes were assessed for microbial levels and for absence from designated microbial species- E.coli, Ps.aeruginosa, S.aureus and salmonella species. The effect of the microbial levels of the raw materials and the formulation technology on the microbial levels of the produced tablets were also investigated. Results indicated that the microbial levels of the tablets were influenced by the microbial quality of the starting raw materials, the production environment and the method of production. Generally, tablets produced by direct compression method gave lower microbial levels than those of the wet granulation method. The compaction process exert lethal effect on the survival of microorganisms. PMID- 1758890 TI - Polymorphism of carbamazepine: solid-state studies on carbamazepine dihydrate. AB - Carbamazepine dihydrate (CBZ.2H2O) crystallizes in the orthorhombic system, space group Cmca or C2ca. The unit-cell constants are: a = 19.834(7), b = 4.945(1), c = 28.826(9) A. M = 272.27, V = 2827(2) A3, Z = 8, D = 1.280 g.cm-3. Indexed X-ray powerder diffraction pattern is given. Dehydration process was studied by means of thermogravimetry and differential thermal analysis: the enthalpy of dehydration was found at 51 kJ per H2O mole. Thermal dehydration leads to an (anhydrous) gamma-form of CBZ when processed in dry atmosphere. The presence of water vapour induces the formation of the beta-form of CBZ as well as the grinding of CBZ.2H2O at room temperature. PMID- 1758891 TI - Influence of different sources on the processing and biopharmaceutical properties of high-dose ibuprofen formulations. AB - It is known that depending on the manufacturing and synthetic processes, drugs may exist as different forms. As a result, physicochemical properties, compression characteristics, intrinsic dissolution and bioavailability may vary substantially. The purpose of this study was to investigate the effect of different sources of ibuprofen on the processing of tablets and on their properties. Another emphasis of this work was to rationalize one or several key characteristics of the raw material as directly related to wet granulation parameters and to the behavior of final tablets. Commercially available ibuprofen was obtained from different manufacturers and a preformulation program, including X-ray crystallography, differential scanning calorimetry, scanning electron microscopy, determination of particle size distribution and flowability, was performed to characterize the raw material. Granules were prepared with a planetary mixer and liquid requirements for the end point were obtained by monitoring power consumption. Tablets were manufactured on Stokes rotary and single punch instrumented presses. Data acquisition interfaces produced compression data for each formulation. Granules and final tablets were analyzed for hardness, dissolution profiles and content uniformity. Statistical evaluations using analysis of variance and multiple comparison procedures were performed on the results to determine the significance of the variability between independent parameters. The ibuprofen tested was found to be a unique polymorphic form with some differences in the external crystallinity. The particle size characteristics of the material also allowed a differentiation between sources and although there was no differences in dissolution patterns or content uniformity, particle size was found to account for 50% of the variability in tablet hardness. Two sources of ibuprofen with lower mean particle size showed significant variations in end point liquid requirements resulting in variable tablet crushing strength. PMID- 1758892 TI - Long-term stability of diazepam injections. AB - Diazepam and its main degradation product 2-methyl-amino-5-chlorobenzophenon (MACB) were quantitatively determined by HPLC and spectrophotometry in one- to ten-years-old diazepam injections. The content of diazepam was within the specifications in all the samples. Not more than 1.5% degradation of diazepam was found after ten years. PMID- 1758893 TI - Doxorubicine englobed in polybutylcyanoacrylate nanocapsules: behaviour in vitro and in vivo. AB - Nanocapsules of polybutylcyanoacrylate containing doxorubicine were prepared from w/o microemulsion. A concentration of about 10% of the drug was obtained. After washing, dispersion and lyophilization of the nanocapsules, some experiments were performed in vivo and in vitro. About 1% of doxorubicine was released in vitro in 48 hours; after injection on the hairless back of rabbits, the nanoparticles without the drug gave any inflammatory processes, while the nanocapsules containing doxorubicine gave a deeper and more prolonged ulcer than that of the same amount of doxorubicine in solution, indicating that practically all the drug was inside the nanocapsules. PMID- 1758894 TI - [The biodisposition of paracetamol. I. The kinetics of disintegration of some dosage forms]. AB - The in vitro properties of twelve brands of paracetamol (nine tablets and three capsules), commercialized in France, are studied. Among the brands tested (tablets), Latepyrine and Gynospasmine are characterized by faster and Panasorb by slower dissolution rate. Total time of dissolution varies between 7 and 60 min. In some brands, paracetamol is liberated from the surface of the disintegrated particles and in others the active principle is released by progressive erosion. The presence of a surface active agent enhances liquid penetration in the case of capsules. PMID- 1758895 TI - [An antiserum directed against phenobarbital with an organometallic tracer: production and characterization]. AB - In order to develop a new immunoassay procedure based on the use of organometallic labels, antisera are raising against sedative-hypnotic drug: phenobarbital. Immunization was performed in rabbits with parasuccinylamidophenobarbital coupled to bovine-serum-albumin. The evaluation of the specificity and the affinity constants of antisera are studied against different hypnotic or antiepileptic drugs and the metallotracer (phenobarbital labelled with an organometallic fragment derived from cymantrene). The most important result of this study indicates that the organometallic moiety of the metallotracer did not disturb neither the inhibition (% inhibition = 110) nor the affinity constant (Ka = 2.10(8) L/M) of the phenobarbital. PMID- 1758896 TI - [Stable copper complexes derived from nitrogen sugars]. AB - This paper describes the synthesis of six new well-defined, stable cupric complexes of the general formula Cu(Ligand)2 in which the organic ligand is a nitrogen-bearing sugar derivative. Some of these compounds showed a border-line cytotoxic activity. PMID- 1758897 TI - Effect of low-molecular casein and gelatin on absorption of ibuprofen after oral and rectal administration. AB - Kneaded mixture of ibuprofen with low-molecular gelatin or casein (LM gelatin or LM casein) was prepared, and their in vitro dissolution, release from suppository base and in vivo absorption behaviours were examined. The dissolution rate of ibuprofen from the kneaded mixtures was markedly higher than that of the drug itself. The LM gelatin and LM casein also enhanced the release rate of ibuprofen from suppository base. After oral administration of the kneaded mixture with LM gelatin to beagle dogs, the initial serum concentration was higher than that of the drug alone. On the other hand, LM casein accelerated the absorption of ibuprofen from rectum. However, LM gelatin and LM casein did not affect the bioinversion of R(-)- to S(+)-ibuprofen. PMID- 1758898 TI - [Magnesium sulfate 4% xylitol infusions solution for the treatment of hypertensive disorders in pregnancy]. AB - A new magnesium sulphate solution with xylitol for the management of hypertensive disorders during pregnancy has been described. The solution contains 40 g MgSO4 and 16 g xylit in 1000 ml and is isoosmotic with blood serum. It can be sterilised for 15 min. at 121 degrees C without risk of decomposition of the ingredients during and after autoclaving. The solution has been proved in the clinical practice. PMID- 1758899 TI - [Polyelectrolyte solution for pediatric PN/TPN mixtures]. AB - Pediatric patients who receive parenteral nutrition (PN) or total parenteral nutrition (TPN) have very high calcium and phosphorus requirements for bone mineralisation. Providing sufficient quantities of these electrolytes is difficult because of calcium and phosphorus solubility limitations in PN-/TPN mixtures. The preparation and the analytical procedure of the special polyelectrolyte solution containing: 30 mmol Ca2+, 30 mmol P, and 20 mmol Mg2+ pro litre is described. The solution is compatible with fat emulsions and other ingredients of all-in-one-solutions. PMID- 1758900 TI - High-pressure liquid chromatographic method for determining adenine arabinoside monophosphate coupled to lactosaminated albumin in plasma. AB - A simple and sensitive method for determining concentrations, in plasma, of adenine arabinoside monophosphate conjugated with lactosaminated albumin is described. It permits the measurement of as little as 0.02 micrograms coupled drug/ml and has considerable advantages over the radioimmunoassay previously used for the same purpose. PMID- 1758901 TI - [Parameters for the formulation of physical-technical characteristics of granules of theophylline obtained by extrusion-spheronization]. AB - Spheroids are prepared from microcrystalline cellulose in binary and compound combination with lactose and theophylline, in certain fixed conditions of extrusion and of spheronisation. The present work envisages the influence of combinated raw materials upon the physical-technique characteristic of the made spheroids. Besides a variation in the granulometric distribution a statical study through analysis of variance brings to the fore that the parameters of formulation contribute to modify the properties of hardness and of friability of the minigranules. PMID- 1758902 TI - [Synthesis, antiparasitic and antifungal activity of aryl-2-thiazolines]. PMID- 1758903 TI - [A comparative study of properties of paracetamol tablets of the matrix type]. AB - Our study was to compare the quantitative and qualitative effects of 2 polymeric agents (methylcellulose, hydroxypropylmethylcellulose) and of 2 diluants (lactose and dicalcic phosphate) on the compression properties and sustained liberation of acetaminophen matrixes. Three experimental plans were permitted the experimentation; regression equations were used for our analysis of the results. The results we obtained show the superiority importance of the effect of the diluant/acetaminophen ratio over the liberation of the drug, as well as the better efficiency of methylcellulosic matrixes. Thence to its solubility, the lactose helps to a faster liberation. PMID- 1758904 TI - Effect of surfactants on the antibacterial activity of preservatives. AB - Antibacterial activities of methyl-p-hydroxybenzoate, phenoxyethanol and chlorocresol against Pseudomonas aeruginosa were evaluated in the presence of varying concentrations of Tween 80. Below cmc level, the bactericidal activities increased with decrease in the surface tension values of Tween 80 solutions and with interfacial tension values of Tween 80 solution/liquid paraffin systems. Linear relationships were found to exist between the concentrations of each preservative required to reduce the microbial population by a factor 10(3) within 48 hours and the values of surface tension and interfacial tension respectively. Reduction in surface tension and interfacial tension would have increased the adsorption and uptake of preservatives by bacterial cells thereby killing the cells at a faster rate. Concentrations of Tween 80 above cmc also enhanced the antibacterial activities of these preservatives. This was attributed to the increase in the permeability of bacterial membranes to preservatives. PMID- 1758905 TI - Growth and survival of Pseudomonas aeruginosa in some aromatic waters. AB - The ability of some aromatic waters at the in-use concentrations to enhance or inhibit the growth of microorganisms was determined by the antimicrobial preservative challenge method. Anise, chloroform, cinnamon, clove, dill, lemon, peppermint and rose waters were challenged with Ps. aeruginosa. Levels of the surviving cells at different times were determined by the pour plate method. The antimicrobial effect of the corresponding undiluted aromatic oils against Ps. aeruginosa was determined by the cup-plate method. Results showed that cinnamon water possesses profound and useful preservative activity against Ps. aeruginosa. The inhibitory effect of anise, chloroform and rose waters on Ps. aeruginosa is not much pronounced. Similarly, clove, dill and peppermint waters exhibited no significant preservative actions. Lemon water was found to enhance the growth of Ps. aeruginosa. The survival pattern of Ps. aeruginosa in the majority of the aromatic waters conforms with the antimicrobial actions of their undiluted oils. PMID- 1758906 TI - [Signs and symbols in early pharmaceutical chemistry. Elements--stars--God]. PMID- 1758907 TI - [Topical agents with an NSAID-base]. PMID- 1758908 TI - [Pharmaceutical development and research at the Humbolt University of Berlin]. PMID- 1758909 TI - [Secondary plant materials as chemical feeding deterrents against herbivorous insects]. PMID- 1758910 TI - [HAMOG. A "new star" in "molecular modeling" programs for the personal computer?]. PMID- 1758911 TI - Methodology and reconstruction. AB - The challenges presented in treating patients with so-called borderline and narcissistic personality disorders have revived interest in the subject of reconstruction, because many analysts believe that these difficulties originate in the events of the earliest preverbal phase of development. They feel that contributions from direct observation of neonates and knowledge gained from "infant psychiatry" may enable analysts to effect reconstructions that previously appeared to be only speculative. The methodological problems in applying this approach, however, may lead to foisting upon clinical observation preconceived paradigms of pathogenesis. Reconstruction depends upon a disciplined interpretation of the dynamic record of the patient's associations, which demonstrate how the past is embedded in the present. The validity of the reconstruction depends upon the application of appropriate and disciplined psychoanalytic methodology. Reconstructions constitute a special form of interpretation and are part of the psychoanalytic process. PMID- 1758912 TI - A reading of Freud's Papers on Technique. AB - Freud's Papers on Technique (1911-1915) is the canonical description of the psychoanalytic procedure. It is a puzzling work because it is dominated by the original paradigm of treatment as memory-retrieval, while at the same time it introduces a new picture, more consistent with Freud's emerging theory of passions, according to which treatment is the stirring up and integration of wishes. I suggest that Papers on Technique becomes less puzzling if we assume that, when he wrote it, Freud was mainly concerned not with theory but with a crucial problem of practice. In exchange for some theoretical inconsistency Freud acquired an important practical advantage, and Papers on Technique uses that advantage to teach analysts how to divide the patient's consciousness into a passionately committed experience, on the one hand, and a detached contemplation, on the other hand, without worrying about the element of manipulation that is involved. The lesson is that a theoretical ambivalence of this sort is essential to the analytic stance. PMID- 1758913 TI - The Biblical Book of Job: advice to clinicians. AB - Study of the Book of Job clarifies the particular adaptation to trauma that underlies the suffering of certain difficult patients. In addition, the misdirected efforts of Job's comforters in the Bible story help us understand why, with such patients, an analyst's attempts to address unconscious guilt and defenses against it will prove counterproductive. A case example is presented. PMID- 1758914 TI - The analysis of an adult with night terror. AB - The author discusses the analysis of a woman with night terror, a condition rarely seen in adults. The analysis revealed the pathogenicity of splitting mechanisms which had developed under the influence of an overstimulating environment and exposure to the primal scene, followed by the separation and divorce of the patient's parents. PMID- 1758915 TI - The "dissolution" of the Oedipus complex: a neglected cognitive factor. PMID- 1758916 TI - Reinforcement in applied settings: figuring out ahead of time what will work. AB - This article reviews the practical value of conceptual attempts to specify the circumstances of reinforcement ahead of time. Improvements are traced from the transituational-reinforcer approach of Meehl (1950), through the probability differential model of Premack (1959, 1965), to the response deprivation and disequilibrium approach (Timberlake, 1980, 1984; Timberlake & Allison, 1974). The application value of each approach is evaluated on the grounds of simplicity, accuracy, and adaptability. The article shows that the disequilibrium approach accounts for and extends current empirically driven techniques of reinforcement control and examines some of its limitations. The disequilibrium approach clarifies how current knowledge can be used to predict more accurately the circumstances of reinforcement and invites the collaboration of applied and basic research in its further development. PMID- 1758917 TI - Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. AB - Advances in the conceptualization and measurement of life stress in the past 2 decades raise several questions concerning traditional diathesis-stress theories of psychopathology. First, comprehensive measures of life stress force investigators to become more precise about the particular stressful circumstances hypothesized to interact with diatheses. Second, the influence of the diathesis on a person's life is typically ignored, which results in several types of possible bias in the assessment of life stress. Finally, information is available on diatheses and stress for specific disorders to provide a foundation for more empirically based hypotheses about diathesis-stress interactions. This possibility is outlined for depression. Such an approach provides the basis for developing broader, yet more specific, frameworks for investigating diathesis stress theories of psychopathology in general and of depression in particular. PMID- 1758918 TI - Culture and the categorization of emotions. AB - Some writers assume--and others deny--that all human beings distinguish emotions from nonemotions and divide the emotions into happiness, anger, fear, and so on. A review of ethnographic and cross-cultural studies on (a) emotion lexicons, (b) the emotions inferred from facial expressions, and (c) dimensions implicit in comparative judgments of emotions indicated both similarities and differences in how the emotions are categorized in different languages and cultures. Five hypotheses are reviewed: (a) Basic categories of emotion are pancultural, subordinate categories culture specific; (b) emotional focal points are pancultural, boundaries culture specific; (c) emotion categories evolved from a single primitive category of physiological arousal; (d) most emotion categories are culture specific but can be defined by pancultural semantic primitives; and (e) an emotion category is a script with both culture-specific and pancultural components. PMID- 1758919 TI - Neuropsychological correlates of hypertension: review and methodologic considerations. AB - Essential hypertension is a chronic disorder having many potential physical and behavioral sequelae. This article evaluates the impact of hypertension on neuropsychological test performance. First, cross-sectional and longitudinal studies that examine the neuropsychological correlates of hypertension are reviewed. In general, hypertensives are found to perform more poorly than normotensives, particularly on tests of memory, attention, and abstract reasoning, and less consistently on tests of perception, constructional ability, mental flexibility, and psychomotor speed. Next, the influence of variables that may moderate relationships between hypertension and neuropsychological performance--such as age, education, and medication usage--are examined. Finally, potential mechanisms, both physiological and psychological, underlying associations between hypertension and neuropsychological performance are discussed. PMID- 1758920 TI - Explanation, imagination, and confidence in judgment. AB - This article concerns a class of experimental manipulations that require people to generate explanations or imagine scenarios. A review of studies using such manipulations indicates that people who explain or imagine a possibility then express greater confidence in the truth of that possibility. It is argued that this effect results from the approach people take in the explanation or imagination task: They temporarily assume that the hypothesis is true and assess how plausibly it can account for the relevant evidence. From this view, any task that requires that a hypothesis be treated as if it were true is sufficient to increase confidence in the truth of that hypothesis. Such tasks cause increased confidence in the hypothesis at the expense of viable alternatives because of changes in problem representation, evidence evaluation, and information search that take place when the hypothesis is temporarily treated as if it were true. PMID- 1758921 TI - The nature of environmental influences on weight and obesity: a behavior genetic analysis. AB - The nature of environmental influences on individual differences in weight and obesity is presently unclear. To resolve this issue, behavior genetic studies are reviewed for their relevance to environmental influences on weight and obesity. Results are consistent in suggesting that environmental experiences are important for weight and obesity, although they account for much less variation than do the effects of genes. Furthermore, only environmental experiences that are not shared among family members appear to be important. In contrast, experiences that are shared among family members appear largely irrelevant in determining individual differences in weight and obesity. These conclusions are consistent with a growing body of evidence on the relative unimportance of such shared experiences for many psychological characteristics. PMID- 1758922 TI - On the relationship between self-focused attention and psychological disorder: a critical reappraisal. AB - A recent review of the literature on the role of self-focused attention in psychological dysfunction (Ingram, 1990) is critically examined. This article (a) reexamines the evidence relevant to Ingram's proposal that self-awareness is a nonspecific factor involved in virtually all forms of psychopathology and argues that this conclusion is not warranted by the existing evidence; (b) takes issue with his premise that the fact that self-awareness is associated with a variety of psychological dysfunctions poses a conceptual dilemma; (c) corrects several important inaccuracies and mischaracterizations in his presentation of Carver and Scheier's (1981) cybernetic control theory and Pyszczynski and Greenberg's (1987) self-regulatory perseveration theory; and (d) critiques the "self-absorption" model that he proposed as an alternative to extant theories and concludes that this conceptualization does not add to the understanding of either self-awareness processes or psychopathology. PMID- 1758923 TI - A framework for the interpretation of first-order interaction in logit modeling. AB - Several suggestions have been tendered for interpreting first-order interaction in log-linear analysis. Occasionally these methods result either in a loss of information or in results that are difficult to grasp on an intuitive level. It is argued that interpreting effect parameters in terms of odds ratios provides an elegant and intuitively appealing conceptual framework that has great generality across models. The interaction term then resembles a cross-product term in linear regression. In both forms of analysis, the partial effect of a given predictor on the response is composed of a constant and a correction that is a function of the other predictor involved in the interaction. This framework is especially appealing for models in which the logit is based on a bifurcation of the dependent variable. Although odds ratios are still useful for summarizing effects on polytomous dependent variables, greater caution must be exercised to avoid misleading interpretations. PMID- 1758924 TI - Misinterpretation of interaction effects: a reply to Rosnow and Rosenthal. AB - The structural model of analysis of variance for multiway tables, with main effects and interaction parameters, is overspecified. Only the set of estimable functions of the cell means is useful. The individual estimates of the parameters are artificial as regards the underlying scientific process. Rosnow and Rosenthal (1989a) stated that it is "absolutely necessary" (pg 146) that interactions should be interpreted by examining the usual estimates of the interaction parameters. This is incorrect. PMID- 1758925 TI - Age differences in the recall of actions and cognitive activities: the effects of presentation rate and object cues. AB - In studies of activity memory, age differences have been found in the recall of cognitive activities (sustained mental activities that subjects solve during acquisition) but not in recall of Subject-Performed Tasks (one-step actions that subjects enact during acquisition). To understand the reasons for the discrepant findings, both types of item were included in a study examining the effects of object cues, rate of presentation, and aging. Variations in presentation rate or use of objects did not account for the different findings on the two item types. Even when presentation rate and object cues were matched, larger age differences were found for recall of cognitive activities than of SPTs. Age differences were also affected by the interaction of item type, presentation rate, and the presence of objects during encoding. To identify the variables controlling age differences, more analysis is needed of the features of activities to be remembered. PMID- 1758926 TI - Blood pressure reactivity and perception of pain during the forehead cold pressor test. AB - The relationship between blood pressure reactivity and the perception of pain was examined during a series of three forehead cold pressor tests given every other day to a group of 18 male college students. Subjects classified as high reactors on the basis of peak increases in mean blood pressure during cold pressor tests perceived the cold pressor stimulus as more painful than subjects classified as low reactors. The propensity to rate the cold pressor stimulus as painful was positively correlated with the individual level of blood pressure reactivity (baseline-free partial r = .62). Intra-individual correlations between pain and blood pressure responses were unrelated to subjects' reactivity status. Across the 3-min test, correlations between pain and blood pressure reactivity (with the effects of baseline blood pressure levels partialled out) were significant only during periods when levels of responses were relatively high. The heart rate responses were unrelated to pain ratings. Generalizability theory was applied to the analysis of temporal stability of cold pressor reactions. Both blood pressure and pain responses were highly reproducible across three sessions, appearing to express stable individual differences. The efficacy of 800 mg oral ibuprofen in controlling the cold pressor pain was also tested. Analgesic activity of the drug during the cold pressor test could not be demonstrated. PMID- 1758927 TI - The effect of repeated testing on ERP components during auditory selective attention. AB - The present study examined long-term repetition effects on human auditory event related potentials (ERPs). ERPs were recorded from subjects performing the same multidimensional auditory selective attention task on six separate occasions spaced one week apart. The task required subjects to attend to tones that varied along the dimensions of location (L), pitch (P), and duration (D) and to detect prespecified target (L + P + D +) combinations of these attributes. Processing negativity (PN) between 100-400 ms did not change in amplitude or onset latency as a function of repeated experience with the task. In contrast, two measures of "very late" PN were reduced with practice. Specifically, the location effect measured over the 400-700-ms epoch was significant only for Weeks 1 and 2, and the separation of the L + P + D- ERP from other D- ERPs, measured over the 700 1000-ms epoch, was significantly reduced from Week 1 to Week 2. A late negative component (700-1000 ms) elicited by correctly identified targets increased between Weeks 1 and 2, consistent with subjects adopting the strategy of rehearsal of the target itself rather than the L + P + D- standard. P2 amplitude increased significantly for all standards, possibly due to decreased latency jitter in later weeks. N1 latency became significantly shorter over weeks, reflecting either increasing confidence in stimulus discrimination with repeated testing or the overlapping of an unchanging N1 with an increasing P2. PMID- 1758928 TI - EEG alpha methodologies and hypnotizability: a critical review. AB - This paper reviews empirical studies that assessed the relationship between EEG alpha indices and measures of hypnotic responding. Although there are confirmatory reports of such a relationship, these findings have not been corroborated in repeated attempts at replication. The research is characterized by poor design and statistical procedures that fail to control for various extraneous factors. Although a few positive findings have been tentatively identified, they await replication. Taken together, the available evidence suggests that hypnotizability is not systematically related to alpha. PMID- 1758929 TI - The truth will out: interrogative polygraphy ("lie detection") with event-related brain potentials. AB - The feasibility of using Event Related Brain Potentials (ERPs) in Interrogative Polygraphy ("Lie Detection") was tested by examining the effectiveness of the Guilty Knowledge Test designed by Farwell and Donchin (1986, 1988). The subject is assigned an arbitrary task requiring discrimination between experimenter designated targets and other, irrelevant stimuli. A group of diagnostic items ("probes"), which to the unwitting are indistinguishable from the irrelevant items, are embedded among the irrelevant. For subjects who possess "guilty knowledge" these probes are distinct from the irrelevants and are likely to elicit a P300, thus revealing their possessing the special knowledge that allows them to differentiate the probes from the irrelevants. We report two experiments in which this paradigm was tested. In Experiment 1, 20 subjects participated in one of two mock espionage scenarios and were tested for their knowledge of both scenarios. All stimuli consisted of short phrases presented for 300 ms each at an interstimulus interval of 1550 ms. A set of items were designated as "targets" and appeared on 17% of the trials. Probes related to the scenarios also appeared on 17% of the trials. The rest of the items were irrelevants. Subjects responded by pressing one switch following targets, and the other following irrelevants (and, of course, probes). ERPs were recorded from FZ, CZ, and PZ. As predicted, targets elicited large P300s in all subjects. Probes associated with a given scenario elicited a P300 in subjects who participated in that scenario. A bootstrapping method was used to assess the quality of the decision for each subject. The algorithm declared the decision indeterminate in 12.5% of the cases. In all other cases a decision was made. There were no false positives and no false negatives: whenever a determination was made it was accurate. The second experiment was virtually identical to the first, with identical results, except that this time 4 subjects were tested, each of which had a minor brush with the law. Subjects were tested to determine whether they possessed information on their own "crimes." The results were as expected; the Guilty Knowledge Test determined correctly which subject possessed which information. The implications of these data both for the practice of Interrogative Polygraphy and the interpretation of the P300 are discussed. PMID- 1758930 TI - Neuroanatomical correlates of skin conductance orienting in normal humans: a magnetic resonance imaging study. AB - Although little is known about the neuroanatomical basis of skin conductance orienting in intact normal humans, the limited literature on animals and humans with neurological and clinical disorders implicate prefrontal, temporal/amygdala, and pons brain areas in mediating skin conductance orienting. This study relates area of these structures using magnetic resonance imaging techniques to skin conductance orienting responses in 17 normal humans in order to test hypotheses that larger area of these excitatory structures will be associated with more orienting responses. Left and right hand skin conductance orienting was significantly associated with left and right prefrontal area (r = .44-.60), area of the pons (r = .43-.54), and left but not right temporal/amygdala area (r = .47 .53). No relationships were observed with areas thought to be unrelated to skin conductance activity (cerebellum, nonfrontal cortical area), medial prefrontal cortex, or the third ventricle. This appears to be the first study relating brain structure to skin conductance orienting in intact normal humans. Although preliminary at the present time, these results implicate prefrontal, pons, and temporal/amygdala areas in the mediation of skin conductance orienting in normal humans. PMID- 1758931 TI - Selective effects of alcohol on electrodermal indices of orienting reflexes to signal and nonsignal stimuli. AB - Effects of a moderate dose of alcohol on the electrodermal orienting reflexes evoked by novel signal, novel nonsignal, and common nonsignal stimuli were assessed. Social drinkers were randomly assigned to the four cells of a balanced placebo design, with 10 males and 10 females per group. They drank a beverage consisting of either tonic water only, or tonic water plus enough vodka to raise blood alcohol levels to approximately .05%. Following drinking and absorption periods, spontaneous and evoked skin conductance responses (SCRs) were recorded. Subjects pressed a footpedal whenever they heard an odd stimulus tone in a series. Alcohol increased the frequency of spontaneous SCRs, increased the number of incorrect pedal-press responses, and selectively enhanced SCRs evoked by the signal tone, p less than .05. Results are interpreted in terms of a hypothesized selective effect of alcohol on frontal cortical inhibitory functions. PMID- 1758932 TI - Phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics in relatives of schizophrenic probands. AB - Abnormalities of visual pursuit tracking are frequent in the first-degree relatives of probands with schizophrenia. The relationship between oculomotor abnormalities and schizophrenia-related characteristics in those family members, however, has received little attention. Fifty-three first-degree relatives of 24 probands with schizophrenia were evaluated for the presence of schizophrenia related characteristics using both interview (Schedule for Schizotypal Personalities) and questionnaire (Chapman scales). The family members also had their eye movements recorded during pursuit tracking tasks and scored for gain in both the frequency and time domains, and saccadic intrusions. Social interpersonal schizophrenia-related features were significantly related to both time- and frequency-domain gain calculations. It appears that abnormalities in the smooth-pursuit oculomotor system may be associated with symptoms conjectured to be most closely related to a genetic diathesis for schizophrenia. These findings provide further evidence that oculomotor abnormalities may be related to risk for this disorder. PMID- 1758933 TI - Modulatory influence of continuous tone, tone offset, and tone onset on the human acoustic startle response. AB - Startle modulation in young adult men, by continuous background tone and its offset, a 2-s sustained tone and its offset, and the onset of a 25-ms tone pip were compared. Tone (75dB 1000 Hz) offset and onset occurred either 2000 ms or 100-120 ms before the startle stimuli (104dB (SPL), 50-ms white noise bursts). Blink amplitude and latency were unaffected by continuous background tone. Blink amplitude was reliably inhibited by 100-ms offset of both the continuous background tone and the 2-s sustained tone or 120-ms onset of the tone pip, whereas effects on latency were more variable. Facilitation of blink amplitude and latency was significant but weak and only following the 2-s sustained tone, and only with respect to one of two experimental contexts. These findings support those of others and suggest that startle inhibition results from activation of neurons responding to transient environmental changes. The degree of inhibition appears to be related to stimulus value. Startle amplitude facilitation following long sustained prestimulation intervals is dependent on experimental context. Overall latency and amplitude modulation tend to be concordant, leading to the conclusion that the mechanism(s) underlying both are context dependent and linked in the adult human. PMID- 1758934 TI - Fear-potentiated startle in humans: effects of anticipatory anxiety on the acoustic blink reflex. AB - The effects of fear/anticipatory anxiety on the acoustic startle reflex were investigated in humans using a paradigm involving anticipation of electric shocks. The eyeblink component of the startle reflex, elicited by an abrupt auditory stimulus, was measured in 9 normal volunteers during either the anticipation of electric shocks (anticipatory anxiety) or periods in which no shocks were anticipated (safe period). The eyeblink was consistently higher in amplitude, and shorter in latency, during periods when the subjects anticipated shocks, compared to the safe periods. This effect could not be attributed solely to a reduction in habituation and was statistically significant before the subjects actually received any shock (a single 30 mA stimulation on the median nerve). These results indicate that anticipatory anxiety can be measured objectively in humans using the fear-potentiated startle reflex in a paradigm not actually requiring any shock. Because a great deal is known about the neuroanatomical and pharmacological mechanisms of fear-potentiated startle in laboratory animals, this test procedure may be especially useful in humans to investigate the neurobiological substrates of anxiety disorders and their pharmacological treatments. PMID- 1758935 TI - Graphical and statistical techniques for cardiac cycle time (phase) dependent changes in interbeat interval. AB - Cardiac cycle time effects refer to the relative lengthening or shortening of a single cardiac cycle as a function of when in the cycle brief sensorimotor events occur. These effects may provide short-latency measures of cardiac sensitivity to psychological events. Conventional representations have, however, failed to clearly separate changes in interbeat interval due to cycle time--i.e., phase dependent changes--from other types of change. This paper advocates a particular technique of plotting to solve these representation problems. Heartbeat timing is represented in real time and in the context of beats both preceding and following the event of interest. The plot, a phase-sensitive plot, conceptualizes phase sensitive (cardiac cycle time) effects as a change in linear or higher order trend. Thus, an adaptation of trend analysis is proposed as an efficient statistical analysis that follows directly from the proposed representational technique. PMID- 1758936 TI - A/D conversion in DMA-mode: problems and solutions. PMID- 1758937 TI - From simplicity to complexity (1950-1990): the case of peptic ulceration--I. Human studies. AB - The problem of the psychobiology of human peptic ulceration has become very much more complicated in the past 20 years, once it was realized that it was not one disease but many. It is recognized that 29 different forms exist. Two common but distinct forms of the disease are characterized by elevated or normal levels of pepsinogen-I. In a third form elevated levels of pepsinogen-II occur; however, this particular increase imparts more of a risk by a factor of 3 for gastric than for duodenal ulcer. In the light of such facts, all studies on the psychological characteristics and social contexts that characterize the onset of the disease must be reevaluated. In addition, a number of different pathophysiological disturbances of the regulation of gastric acid secretion, motility, and bicarbonate secretion characterize patients with the disease, and further subdivide patients with increased or normal pepsinogen-I levels. PMID- 1758938 TI - From simplicity to complexity (1950-1990): the case of peptic ulceration--II. Animal studies. AB - Considerable progress has been made in the understanding of the formation of gastric erosions in rats. The role of gastric acid secretion in their pathogenesis has been clarified. Gastric erosions are also associated with slow gastric contractions. With several experimental procedures, the body temperature falls; preventing this decrease averts erosions. A fall in body temperature or exposure to cold is associated with the secretion of thyrotropin-releasing hormone (TRH), and both an increase and decrease in corticotropin-releasing factor (CRF) in discrete regions of rat brains. TRH produces gastric erosions, increases in acid secretion, and slow contractions, while CRF has the opposite effects. One of the major sites of interaction of the two peptides is in the dorsal motor complex of the vagus nerve. TRH increases serotonin (5-HT) secretion into the stomach. 5-HT counter-regulates acid secretion and slow contractions. Many other peptides stimulate or inhibit gastric acid secretion. PMID- 1758939 TI - Biobehavioral basis of coronary-prone behavior in middle-age men. Part II: Serum cholesterol, the Type A behavior pattern, and hostility as interactive modulators of physiological reactivity. AB - Prior research suggests that the Type A behavior pattern, Cook and Medley Hostility (Ho) scores, and Total Serum Cholesterol (TSC) are positively associated with physiological changes to behavioral stressors. The objective of the present study was to determine whether TSC interacts with the Type A behavior pattern and hostility to affect cardiovascular and neurohormonal responses to a mental arithmetic task (MATH). For Type A individuals, elevated TSC was associated with larger catecholamine and cortisol responses to MATH. In contrast, for Type B subjects, cholesterol was negatively associated with neurohormonal responses. The interaction between Ho score and TSC predicted a similar pattern of responses whereby, in high hostile men only, TSC was positively associated with MATH-induced changes in catecholamines and heart rate. While the mechanisms responsible for the differences in the lipid-reactivity association as a function of coronary-prone behavior measures remain to be elucidated, this differential association may play a role in the heightened risk of coronary disease among hostile Type A men. PMID- 1758940 TI - Negative affectivity and repressive coping: pervasive influence on self-reported mood, health, and coronary-prone behavior. AB - Negative affectivity (NA) and repressive coping (REP) are coping styles characterized by a disposition to either experience or avoid distress. This study investigated the potential influence of NA and REP on self-reported distress and coronary-prone behavior among 178 male cardiac patients undergoing rehabilitation. Based on their STAI-Trait and Marlowe-Crowne Scale scores, subjects were categorized as high NA (N = 72), low NA (N = 44), or REP (N = 62) individuals. With respect to subjective distress, high-NA individuals reported more negative mood states and health complaints than both low-NA and REP individuals (p less than 0.0001). In contrast, no association was found between coping style and cardiovascular fitness as measured by exercise stress testing (p = 0.87). Hence, it seems that (a) high-NA individuals overreacted to physical problems and (b) REP individuals warded off distress. These differences in coping style were stable over a period of 3 months. With respect to coronary-prone behavior, the current findings were largely inconsistent with previous research. NA was associated with Type A interview-rating (p less than 0.001), but not with Type A self-rating. REP individuals, however, had a significantly lower score on the Jenkins Activity Survey and the Cook-Medley Hostility Scale than both high-NA and low-NA individuals (p less than 0.0001). Supposed associations, therefore, between NA and self-rated coronary-prone behavior may in fact originate from the repressive coping style that characterizes some individuals low in NA. In summary, it may be stated that the findings of the current study suggest the use of NA and REP markers in research, so that the potential influence of these coping styles can be identified in the study of stress-health relationships. PMID- 1758941 TI - Prevention of arousal-induced hyperlipidemia by glucose ingestion. AB - Thirteen subjects were investigated to compare the effects of pre-event glucose (G) and placebo (P) ingestion on plasma free fatty acid (FFA) concentration during mental work. Subjects performed two trials of a videogame and received money for each point scored. Thirty minutes before commencing each trial, subjects ingested either a solution containing 50 g of G or an identically sweetened and colored placebo. Order of ingestion was partially counterbalanced. Heart rate, the measure of arousal monitored, increased significantly above baseline during each trial, but there was no difference in this rise between trials. The main finding from this experiment was that after ingesting glucose, subjects had a stable blood FFA concentration during the videogame, while after the ingestion of placebo subjects had a significantly higher blood FFA during videogames than they had at baseline. These data suggest that arousal-induced hyperlipidemia can be prevented by pre-event glucose ingestion. PMID- 1758942 TI - Coping and extreme response tendency in duodenal ulcer patients. AB - In this study we examined problem- and emotion-focused coping in samples of 30 duodenal ulcer (DU) patients and 30 matched healthy controls. Coping processes were assessed for two stressful situations, viz, an interpersonal conflict and a difficult task or job. The results indicated that DU patients and controls did not differ in terms of preferred coping strategies: irrespective of type of stressor, no differences were found between the two samples, neither in terms of a more general inclination toward problem- or emotion-focused coping, nor in terms of separate, more fine-grained coping mechanisms. Furthermore, rating extremity was studied in both samples. It was found that DU patients have a tendency to endorse extreme positive responses ("Very characteristic of me") more often than controls. The latter finding is discussed in terms of competing explanations: (a) higher polarizing tendencies of DU patients vs. (b) higher meaningfulness of the questionnaire items for DU patients. Specific directions for future research are described. PMID- 1758943 TI - A naturalistic study of the relationships among electromyographic activity, psychological stress, and pain in ambulatory tension-type headache patients and headache-free controls. AB - Twelve subjects who met diagnostic criteria for episodic tension-type headache and nine subjects who rarely or never suffered from headaches wore a computer controlled electromyographic (EMG) activity recorder in their natural environment for 48 to 96 consecutive hours. EMG activity of the posterior neck or frontal muscles was recorded 24 hr per day. During waking hours, subjects rated their perceived levels of stress, pain, and negative affect at 30-min intervals. The EMG activity of headache and control subjects did not differ significantly, and EMG activity did not covary with stress, pain, or negative affect. Cross correlations among EMG activity, pain, and stress revealed little evidence of leading, contemporaneous, or lagging relationships. Interrupted time series analysis showed no consistent muscle hyperactivity during a headache attack compared to a headache-free baseline period. PMID- 1758944 TI - Relaxation behavior therapy as sole treatment for mild hypertension. AB - This study tested the efficacy of relaxation therapy as sole treatment for mild hypertension in 110 men and women recruited from a five-stage worksite blood pressure screening program. Participants were randomized to 12-weeks of relaxation therapy or support therapy. Outcome blood pressure assessments made by assessors who were unaware of group allocation revealed similar decreases in both treatment groups at post-treatment and 6-month follow-up. While body weight did not change, alcohol consumption decreased similarly in both groups, and alcohol consumption was positively correlated with both absolute diastolic blood pressure and change in diastolic blood pressure at outcome. In conclusion, a superior blood pressure effect was not associated with relaxation therapy; however, alcohol consumption decreased in both treatment groups, suggesting that both interventions facilitated changes in health risk behaviors and indirectly on blood pressure level. PMID- 1758945 TI - Social network and blood pressure: a population study. AB - The relationship between social network and blood pressure was assessed in a cross-sectional, random sample of 1409 white adults aged 20 to 70 years studied in Buffalo in 1961. Higher total social network scores were associated with lower systolic and diastolic blood pressure in both males and females. Considering the components of social network separately, increased size of household and greater participation in clubs were associated with lower systolic blood pressure for males, with the trend in the same direction for women, though not reaching statistical significance. Among females, the only social network component showing significant linear trend was the number of siblings, with increased number of siblings being associated with lower systolic and diastolic blood pressure. Religious service attendance and marital status were not associated with blood pressure in this population. PMID- 1758946 TI - Social support, lifestyle incongruity, and arterial blood pressure in a southern black community. AB - Social support is generally thought to modify or "buffer" the impact of stressful events and circumstances on health. There has been little exploration of how the definition and effect of support is modified by culture. In this paper, the role of social support in moderating the effect of a social stressor on arterial blood pressure is examined in a southern black community. Traditionally, support was available mainly within the extended family in African-American culture. In the aftermath of social change, however, younger black people often find their experiences to be more consonant with their peers. It was hypothesized that kin support would moderate the effect of status incongruence on blood pressure for older persons, while nonkin support would moderate the effect for younger persons. This hypothesis was confirmed in a community study. Future research on social support, therefore, must take into account cultural factors influencing the meaning of social support from different sources. PMID- 1758947 TI - The effects of masculinity and social support on recovery from myocardial infarction. AB - Ninety post-myocardial infarction (MI) patients were interviewed to assess masculinity/femininity and social support shortly before hospital discharge. Patients were contacted 1 year following MI to obtain information about rehospitalization and/or death, post-MI chest pain, and perceived health. After controlling for traditional coronary risk factors, MI severity, and psychological distress, lack of disclosure to one's spouse predicted worse recovery on all three indices. Exploratory analyses revealed that males (n = 63) who disclosed to their spouses were rehospitalized less often than females (n = 14) who disclosed to their spouses, and married patients who engaged in less spouse disclosure (n = 32) were significantly more likely to be rehospitalized than either unmarried patients (n = 14) or married patients who engaged in more spouse disclosure (n = 41). Masculinity predicted more severe post-MI chest pain but was unrelated to rehospitalization and perceived health. PMID- 1758948 TI - The effects of fat and cholesterol on social behavior in monkeys. AB - We report here on the social behavior of 30 adult male cynomolgus monkeys, maintained in social groups of five animals each and assigned for 22 months to one of two dietary conditions: a) "luxury"--relatively high fat, high cholesterol (43% calories from fat, 0.34 mg cholesterol/Calorie of diet); or b) "prudent"- relatively low fat, low cholesterol (30% calories from fat, 0.05 mg cholesterol/Calorie of diet). The dietary manipulation resulted in higher total serum cholesterol (TSC) and lower high density lipoprotein cholesterol (HDLC) concentrations in luxury diet animals than in their prudent diet counterparts (p's less than 0.05). Additionally, we monitored the occurrence of 21 behavioral acts frequently exhibited by this species in captivity. Of these behaviors, only contact aggression differed between dietary conditions (p less than 0.03), with prudent diet monkeys initiating more aggression than luxury diet animals. These results are consistent with studies linking relatively low serum cholesterol concentrations to violent or antisocial behavior in psychiatric and criminal populations and could be relevant to understanding the significant increase in violence-related mortality observed among people assigned to cholesterol-lowering treatment in clinical trials. PMID- 1758949 TI - Platelets and coronary heart disease: potential psychophysiologic mechanisms. AB - Although there has been extensive research attempting to identify psychophysiologic mechanisms linking psychological events and behavior patterns with risk for coronary heart disease, these are important potential mechanisms that remain largely unexplored. One of these mechanisms is thrombosis, which is widely recognized as the precipitant of acute coronary events (myocardial infarction and sudden ischemic death). A major element in arterial thrombosis is the platelet, and platelet inhibition has been shown to be effective in preventing coronary events. In the present paper, platelet physiology and pathophysiology are reviewed. Platelet function testing and the clinical role of platelet activation in atherosclerosis and acute coronary events are also discussed. Because epinephrine and possibly shear stress are clinically important activators of platelets, it is proposed that platelet reactivity to psychological stress may be a major mechanism in coronary events. The literature to date supports the hypothesis that platelet activity is increased by emotional stress. Suggestions are made for future research in this area. PMID- 1758950 TI - Depression and type A behavior pattern in patients with coronary artery disease: relationships to painful versus silent myocardial ischemia and beta-endorphin responses during exercise. AB - A sample of 45 patients with a history of coronary heart disease and documented myocardial ischemia during exercise testing were evaluated in an investigation of the possible relationships between psychological factors (depression and Type A behavior pattern), plasma beta-endorphin response and pain experience during maximal exercise-induced ischemia. Depression was assessed using the MMPI-D subscale, while Type A was evaluated using the Structured Interview. All patients developed ischemia during exercise as defined by ST-segment depression; however, only 18 patients reported anginal pain. Patients with high depression scores (MMPI-D greater than or equal to 70; n = 13) showed lesser increases in plasma beta-endorphin levels, tended more often to report anginal pain and rated pain as more severe during exercise than patients with low depression scores (MMPI-D less than 60; n = 18). Hemodynamic responses and severity of ischemia (assessed by ejection fraction changes and wall-motion abnormalities) did not differ between depression groups. Even after adjustment for group differences in exercise duration, depression was significantly associated with a lesser beta-endorphin response in the sample as a whole and, among patients reporting angina, with earlier pain onset and greater pain duration and severity. In contrast, when Type A versus B/X subgroups were compared, no differences in pain experience, beta endorphin response or measures of ischemia were obtained. These findings suggest that in patients with ischemic heart disease, there may be a relationship between depression and anginal pain which may in part involve a blunted or absent beta endorphin response. PMID- 1758951 TI - Cynical hostility in adult male twins. AB - The heritability of hostility as measured by the Cook and Medley Ho scale was assessed in an adult male sample of 60 monozygotic and 61 dizygotic twin pairs. For the total Ho scale, as well as its health predictive component, the results were consistent with a moderate genetic effect. Results are discussed in terms of genetic and environmental influences on the development of this trait, and possible genetic contributions to the association between hostility and subsequent health. PMID- 1758952 TI - Quantitative assessment of olfactory experience during pregnancy. AB - Results of the National Geographic Smell Survey were used to investigate the effects of pregnancy on olfactory perception and odor-related behavior. The responses to test odors and survey questions of 13,610 pregnant and 277,228 nonpregnant U.S. women between 20 and 40 years of age were analyzed. In comparison to nonpregnant women, pregnant women rated their own sense of smell lower, more often rated the test odors less pleasant smelling, more often classified the test odors as inedible, were less likely to report odor-evoked memories, and used perfume and cologne less frequently. Differences in odor detection and intensity rating did not favor either group. PMID- 1758953 TI - The rating form of IBD patient concerns: a new measure of health status. AB - Health status assessment for persons with chronic illness includes not only symptoms, but also an appraisal of the psychosocial concomitants of illness. In this national study of persons with inflammatory bowel disease (IBD), we standardized a disease-specific 25-item measure of perceived health status: the Rating Form of IBD Patient Concerns (RFIPC). Factor analysis yielded four indices: a) impact of disease (e.g., being a burden, loss of energy, loss of bowel control); b) sexual intimacy; c) complications of disease (e.g., developing cancer, having surgery, dying early); and d) body stigma (e.g., feeling dirty or smelly). A higher level of IBD concerns was associated with greater disease severity, female gender, and lower educational status. When controlling for these factors, as well as disease type and age, we found that concerns about: a) impact of disease was positively associated with poorer perception of health and well being, greater psychological distress (SCL-90), and poorer daily function (Sickness Impact Profile) (p less than 0.0001); b) sexual intimacy was related to poorer psychologic function (p less than 0.01); and c) complications of disease was related to several measures of poorer daily function (p less than 0.0001 to 0.01). This standardized measure of the worries and concerns of persons with IBD may be used in clinical care and research to evaluate the effects of interventions on IBD patient outcomes. PMID- 1758954 TI - Affect, emotional conflict, and deficit: an overview. PMID- 1758955 TI - Multiple sclerosis: the impact of physical impairment and cognitive dysfunction on social and sparetime activities. AB - In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled suffered from severe psychosocial strain. The literature shows that the strain becomes even more severe in certain periods of progression of the disease with the result that psychosomatic conditions arise. PMID- 1758956 TI - Psychodynamic aspects of psychopharmacology in functional somatic complaints. AB - Psychiatrists as well as general practitioners frequently prescribe psychotropic drugs (tranquilizers such as benzodiazepines and increasingly low-dose long acting neuroleptics) to treat functional organic complaints. We are interested in finding out the psychodynamics in the doctor-patient relationship that determine whether the doctor puts more emphasis on eliminating symptoms by prescribing psychotropic drugs or on solving the underlying conflicts by psychotherapy. Furthermore we describe some interactions which are of importance for illustrating whether drugs are effective or lead to side effects. PMID- 1758957 TI - Ego defensive styles and alexithymia: a discriminant validation study. AB - Fifty-six mildly depressed psychiatric outpatients were evaluated for alexithymia measured by the Toronto Alexithymia Scale. Each subject also completed a Defensive Style Questionnaire that assessed the maturity of their ego defenses. Alexithymia was strongly associated with immature ego defenses, but not with depression. The data suggests that alexithymia and such primitive defensive operations are separate phenomena. These findings empirically support earlier observations regarding the nature of alexithymia. PMID- 1758958 TI - Outcome of gastric surgery for morbid obesity: weight changes and personality traits. AB - This controlled study explores weight change in relation to certain personality and behavioural characteristics in a population of morbidly obese individuals who have undergone a gastric procedure to lose weight. In particular, measures of alexithymia and symbolic function were used, and the results of the study indicate that these concepts are particularly helpful in understanding obese individuals, and aetiology and treatment of their condition. PMID- 1758959 TI - Group therapy with elderly patients. AB - In our research we try to suggest a type of group therapy for elderly patients to favor the communication process and to make the patient acquire an active role in the group. The group has an open structure with weekly sessions that last one hour and a half each. The group is conducted by therapists who coordinate the work, acting as stimulus and supporting the relationship between the patients. It is composed of 8 patients, some of whom have been inpatients of the department while others were sent by territorial social service. Age is not the only component for selection; above all, problems regarding loneliness, difficulties in interpersonal relationships and consequent loss of contact and interest in the other are considered. PMID- 1758960 TI - Morbid obesity: effects on the marital system of weight loss after gastric restriction. AB - Eighty morbidly obese married women and 69 of their husbands completed a self report measure of personal and marital adjustment before the women proceeded to gastric restriction surgery. Fifty-five women and 41 husbands repeated the measure 12 months after surgery, at which time the women had lost a mean of 35.4 kg. Women rated themselves as significantly more attractive and sociable, and rated their husbands as significantly less sociable and interesting, than before surgery. Husbands rated their wives as excessively sociable after surgery, the reverse of their previous view. The data offered some support for a family systems view of morbid obesity, but the systemic effect appeared weak, and is probably not a major contributor to wives' morbid obesity in most cases. PMID- 1758961 TI - Exploring the doctor-patient relationship reduces staff stress and enhances empathy when caring for AIDS patients. AB - At our AIDS outpatient clinic we presently care for more than 1,200 HIV-infected patients. All physicians in this unit have participated for 1 year in a case work group supervised by a liaison psychiatrist. The doctor-patient relationship, the assessment in the case work group and the ensuing influence on perception and behavior are demonstrated by 3 cases. Different issues challenge the doctor patient relationship: the serious prognosis of predominantly young AIDS patients; isolation and stigmatization of patients; fear of contagion, and questions of confidentiality regarding contact tracing. Reflection upon the doctor-patient relationship improves communication skills and increases empathy towards AIDS patients. PMID- 1758962 TI - Observing countertransference in brief dynamic psychotherapy. AB - Six cases treated with Brief Dynamic Psychotherapy were studied. Initial countertransferential reactions were identified, and expectations were determined concerning the evolution of the patient-therapist relationship. The existence of a basic pattern of emotional response to the patient in the therapist throughout the treatment was observed, and the authors propose to denominate it countertransferential focus. Three clinical vignettes are reported. PMID- 1758963 TI - The use of the carp retina in neurobiology: its uniqueness and application for neural network analyses of the inner retina. PMID- 1758964 TI - Development of the cerebellum and its extracerebellar Purkinje cell projection in teleost fishes as determined by zebrin II immunocytochemistry. PMID- 1758965 TI - Brain activity patterns: assessment by high resolution autoradiographic imaging of radiolabeled 2-deoxyglucose and glucose uptake. PMID- 1758966 TI - [The value of the Thematic Apperception Test (TAT) for diagnosis and therapy of borderline personality disorders]. PMID- 1758967 TI - [The finite and infinite development. II. Recent psychoanalytic theory and therapeutic considerations]. AB - Freud's characterization of the manifest dream is typified by an implicit appreciation and an explicit devaluation of dream images. According to the author, the theoretical-historical motive behind this divergent evaluation is already evident in Freud's prepsychoanalytic writings, where he assigns primacy to the written word. The author holds that the biographic motive derives from an ambivalent internalization of the Mosaic sanction against graven images, conveyed to Freud by his father through the spirit of the Phillipson Bible. PMID- 1758968 TI - [Importance of regression to dependency]. PMID- 1758969 TI - [Current aspects of a psychoanalytic culture theory]. PMID- 1758970 TI - Sprouting of aberrant neuropeptide Y-immunoreactive sympathetic nerves into neonatally denervated smooth muscle. AB - Sympathetic nerves normally project ipsilaterally to lateral cranial targets. Following unilateral superior cervical ganglionectomy in neonatal rats, however, neurons from the contralateral superior cervical ganglion sprout into the denervated region. In the present study we examined neuropeptide Y immunoreactivity (NPY-ir) of neurons comprising ipsilateral (control) and denervation-induced contralateral pathways to the superior tarsal smooth muscle of the eyelid. Fluoro-Gold injection of the control muscle retrogradely labelled 133 +/- 18 neurons in the ipsilateral superior cervical ganglion; of these, 21 +/ 3% displayed detectable NPY-ir. Fluoro-Gold injections of the reinnervated muscle labelled 20 +/- 4 neurons in the contralateral superior cervical ganglion, of which 85 +/- 3% contained detectable NPY-ir. Examination of the control tarsal muscle revealed DBH-ir noradrenergic nerves throughout the muscle and vasculature, while NPY-ir nerves were present primarily around blood vessels. In the reinnervated preparation, NPY-ir fibers innervated both blood vessels and tarsal muscle in a pattern similar to that of DBH-ir innervation. Acute excision of the remaining superior cervical ganglion eliminated all DBH-ir fibers bilaterally; NPY-ir was reduced markedly in the reinnervated preparations, though some fibers remained. We conclude that, following neonatal denervation, the tarsal muscle is reinnervated by a subpopulation of sympathetic neurons that differs in neuropeptide phenotype from that of the normal ipsilateral innervation. PMID- 1758971 TI - The effect of HP-1 and related neutrophil granule peptides on DNA synthesis in HL60 cells. AB - The recently isolated cysteine- and arginine-rich peptides of the neutrophil primary granule and the murine intestinal Paneth cell, named defensins or corticostatins, have a number of distinct biological properties. We report the effects of three of these peptides HP-1, HP-1-56 and HP-4 on the incorporation of [3H]thymidine into the DNA of the leukemic cell line HL60. HP-1 and HP-1-56, but not HP-4, inhibited DNA synthesis at 1-50 nM without causing cell death. At higher concentrations the effect was reversed, resulting in a small, but statistically significant increase in DNA synthesis at 1 microM. In contrast HP-4 had no effect on HL60 cells at nanomolar concentrations but was strongly cytotoxic at micromolar concentrations. PMID- 1758972 TI - Chromatographic characterisation and biological activity of neuropeptides immunoreactive to antisera against Met5-enkephalin-Arg6-Phe7 (YGGFMRF) extracted from the blowfly Calliphora vomitoria (Diptera). AB - Neuropeptides identified with a radioimmunoassay specific for the C-terminus of Met5-enkephalin-Arg6-Phe7 (YGGFMRF) have been extracted from nervous tissues of the blowfly Calliphora vomitoria and also from whole flies. Chromatographic characterisation, based on criteria of molecular weight, charge and hydrophobicity, reveals a complex multiplicity of immunoreactive peptides. Variations in the amounts and types of peptides found within different nervous tissues is evidence that the cellular precursor processing is selective. Physiological studies on the isolated blowfly salivary gland show that synthetic YGGFMRF is a potent secretagogue with a maximal rate of fluid secretion induced at a concentration of between 10(-13) and 10(-12) M. The tetrapeptide comprising the last four residues of the C-terminus of YGGFMRF, Phe-Met-Arg-Phe, is equally potent. However, the carboxyamidated variants, YGGFMRF-NH2 and the molluscan cardioacceleratory peptide FMRF-NH2, as well as the opioid peptides Met5- and Leu5-enkephalin, have no activity. Partially purified YGGFMRF-immunoreactive peptides from the blowfly have ED50 values in the bioassay approximating to 0.3 thoracic ganglion, 2.1 hypocerebral ganglion and 3.0 brain equivalents. PMID- 1758973 TI - Reduced cholecystokinin in the brain of LEC rats with hepatic encephalopathy. AB - Levels of cholecystokinin (CCK) immunoreactivity and distribution of CCK immunoreactive cells were studied in the cerebral cortex of LEC (Long Evans Cinnamon) rats with hepatic encephalopathy. CCK immunoreactivity in water extract of cerebral cortex of LEC rats with hepatic encephalopathy (n = 7) was 41.5 +/- 2.6 (mean +/- S.E.M. pmol/g wet wt.) and that of LEC rats without encephalopathy (n = 8) was 67.1 +/- 6.9, the difference being significant (P less than 0.01). CCK immunoreactive cells assessed by immunohistochemistry were also markedly decreased in the cortex of LEC rats with hepatic encephalopathy of stage IV. Thus, CCK reduction was observed in the cerebral cortex of LEC rats with hepatic encephalopathy which are provided as a model for analysis of the pathogenesis of acute hepatic encephalopathy. PMID- 1758974 TI - Elucidation of the sequence of canine (pro)-calcitonin. A molecular biological and protein chemical approach. AB - From the canine thyroid gland a calcitonin (CT) immunoreactive peptide was purified by successive aqueous acid acetone extraction, gel filtration and HPLC. Gas-phase sequencing of the purified peptide showed that the first 25 amino acids had 65% sequence homology with the amino-terminus of the human CT prohormone. A canine cDNA library was then made from the thyroid gland. A plasmid was isolated containing a sequence that is homologous to part of exon 3, and the complete sequence of exon 4 of the human mRNA encoding preproCT. From this cDNA the amino acid sequence of canine CT is predicted. In comparison with well-known CT sequences of other species, the strongest homology exists with bovine, porcine and ovine CT. PMID- 1758975 TI - Neuromedin-N inhibits migrating myoelectric complex and induces irregular spiking in the small intestine of rats; comparison with neurotensin. AB - The effects of neuromedin-N on migrating myoelectric complexes in the small intestine of rats were studied. As neuromedin-N and neurotensin are structurally related peptides a comparison with neurotensin was made. Myoelectric activity was recorded by means of three bipolar electrodes implanted into the wall of the small intestine at 5, 15 and 25 cm distal to the pylorus. The peptides were administered as intravenous infusions to fasted conscious rats. Neuromedin-N at doses of 100-800 pmol kg-1 min-1 caused a dose-dependent disruption of the migrating myoelectric complexes and induced irregular spiking activity (n = 7, P less than 0.05). Neurotensin induced a similar response, but at doses of 1.0-8.0 pmol kg-1 min-1 (n = 5, P less than 0.05). Thus, on a molar basis, neuromedin-N appeared to be about 100-times less potent than neurotensin. Hexamethonium (20 mg kg-1 i.v.) inhibited the migrating motor complexes and induced quiescence, but did not block the effect of neuromedin-N at a dose of 800 pmol kg-1 min-1. Atropine (1 mg kg-1 i.v.) and mepyramine (2 mg kg-1 i.v.) did not affect the migrating motor complexes, nor did they block the effect of neuromedin-N. Simultaneous infusion of neuromedin-N and neurotensin in a 1:1 molar ratio at doses of 2 pmol kg-1 min-1 showed inhibition of the response to neurotensin in eight out of ten experiments. In conclusion, neuromedin-N changes the myoelectric activity in the small intestine from a fasting to a fed pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1758976 TI - Bombesin-like immunoreactivity in skates and the in vitro effect of bombesin on coronary vessels from the longnose skate, Raja rhina. AB - Bombesin-like immunoreactivity is present in nerve fibers projecting to the cardiovascular system, including the coronary arteries, and to the gastrointestinal canal, and in endocrine cells of the gut of skates belonging to the family Rajidae. Synthetic bombesin contracted isolated coronary rings from the longnose skate, Raja rhina, in a cumulative fashion. The contractile response was 84% of that of 60 mM potassium chloride. The pD2-value for bombesin was 8.83 (S.E.M. = 0.33; n = 15). Phentolamine, atropine and two substance P-antagonists increased the sensitivity to bombesin, while atenolol, sotalol, nifedipine, tetrodotoxin and two bombesin antagonists were devoid of significant effects. We conclude from this study that a bombesin-like peptide is present in nerves innervating the cardiovascular system and the gastrointestinal canal of skates of the family Rajidae, and that bombesin contracts coronary vessels in vitro via a direct mechanism and/or via mechanisms involving alpha-adrenergic and muscarinergic receptors. PMID- 1758977 TI - Gastrin/CCK antagonists and their use in gastrointestinal research. Bayliss and Starling Society 11th annual meeting. Liverpool, 23-24 September 1991. PMID- 1758978 TI - Children of alcoholics. PMID- 1758979 TI - A revised estimate of the economic impact of fetal alcohol syndrome. AB - A revised estimate of the national economic impact of fetal alcohol syndrome (FAS)-related abnormalities was conducted. The present evaluation included "corrections" for background rates of low birth weight, and costs normally incurred for housing and food regardless of whether an individual requires institutionalization or not. Additional anomalies were included along with hospital costs provided for in diagnostic-related groups. The current estimate for annual costs related to FAS is $249.7 million, which is about $80 million less than our previous estimate. This estimate is lower due to a slightly lower number of cases with low birth weight, a correction for costs that would otherwise have occurred, and exclusion of costs (about $75 million) for annual semi-independent support for individuals with IQs in the 70-85 range. Nonetheless, mental retardation accounts for almost 60% of the estimated total cost. A quarter of a billion dollars per year remains a high economic incremental cost by any reasonable standard and represents a benchmark against which costs of potential prevention strategies may be judged. PMID- 1758980 TI - Clinical correlations between ethanol intake and fetal alcohol syndrome. AB - Fetal alcohol syndrome (FAS) is a cluster of features observed in some offspring of women who abuse alcohol in pregnancy. The defining features include intrauterine growth retardation, specific craniofacial dysmorphology, and central nervous system dysfunction. FAS is a full expression of a continuum of fetal alcohol effects. The assessment of alcohol abuse is one of several major problems in the study of the topic. Research findings are reviewed under a hypothesis of increasing effect in ordered categories: lethal effects, adverse obstetrical outcomes, malformations, growth retardation, reduced head circumference, and neuropsychological effects. Evidence of fetal alcohol effects may be found for each outcome category. The evidence across studies is not consistent nor is there any clear support for an effect order. The risk for psychological deficit may depend on the presence of dysmorphic effects. PMID- 1758981 TI - The effects of prenatal alcohol on the central nervous system. AB - Prenatal alcohol exposure has a profound effect on the developing brain. In fetal alcohol syndrome (FAS), mental retardation and microcephaly are commonly observed. A partial syndrome, fetal alcohol effects (FAE) can result in neurobehavioral sequelae, which may present at birth or appear later in development. This chapter discusses the clinical evidence supporting the concept of FAE, the range of cognitive disturbances seen in FAS and FAE children, and studies on long-term outcome. We review studies that suggest that even in the absence of the stigmata of FAS, neonatal signs of central nervous system dysfunction may predict later developmental deviation. However, the clinical research on the cognitive and behavioral disorders in the FAE population is limited. Examination of electroencephalograms, evoked potentials, and sleep pattern provide additional evidence that the functional integrity of the brain has been altered. An abbreviated review of behavioral animal studies provides additional support for the clinical investigations presented. PMID- 1758982 TI - Multilevel intervention for prevention of fetal alcohol syndrome and effects of prenatal alcohol exposure. AB - The deleterious effects of prenatal alcohol exposure have been the subject of numerous research studies since first recognized in the early 1970s. The results of these studies have indicated that the dose and patterning of maternal alcohol consumption, use of other drugs, as well as other social and environmental factors may mediate developmental outcomes in prenatally alcohol-exposed children. Although there are still many unanswered questions regarding etiology, there is a clearly identified need for effective prevention/intervention programs for alcohol-abusing women of childbearing age. Such programs must address the multiple factors that may exacerbate alcohol's teratogenic effects. The prevention of fetal alcohol syndrome (FAS) and other alcohol-related birth defects (ARBD) can only be accomplished through multilevel, multisystem intervention strategies, including community education, therapeutic interventions with the alcohol-abusing mother, parenting education, and early identification and intervention with the alcohol-affected child. A review on the etiology of FAS and ARBD is presented with recommended strategies for prevention/intervention. PMID- 1758983 TI - Vulnerability to alcoholic liver disease. AB - Epidemiological evidence suggests a direct relationship between alcohol consumption and the prevalence of cirrhosis. However, the observation that only 8 30% of alcoholics develop cirrhosis illustrates that individual susceptibility mediates the relationship between alcohol consumption and cirrhosis. This chapter examines the factors that may influence individual risk for alcoholic liver disease. These factors include individual differences in alcohol metabolism and consumption patterns, gender, HLA antigens, family alcoholism history, and immune responsiveness. Important methodological issues in each of these areas are addressed also. From the available evidence, the hypothesis is advanced that there is an underlying vulnerability to liver disease in some individuals, and that alcohol use, although a necessary condition, is not sufficient to trigger disease in all individuals. PMID- 1758984 TI - Hepatic encephalopathy coexistent with alcoholism. AB - Although it is well established that the majority of alcoholics are neurologically compromised, little is known about the etiological factors underlying the central nervous system (CNS) disturbances. Without doubt, ethanol is a neurotoxin; however, the complex array of factors presaging drinking onset and factors concomitant to a lifestyle of alcohol abuse probably also influence the risk for neurologic injury. This chapter reviews the emerging evidence linking liver disease to the neurologic pathology manifested by chronic alcoholics. The observation that the pattern and severity of cognitive deficits is similar between alcoholics and nonalcoholics with cirrhosis, combined with the demonstration that biochemical indices of liver injury correlate with cognitive test performance in alcoholics, illustrates the important role of liver disease as a codeterminant of the CNS disturbance. In addition, the findings from developing research indicating that liver transplantation can reverse the deficits on neuropsychological tests further underscore the importance of advanced liver disease as a determinant of the CNS pathology, and the results suggest the need for aggressive treatment of alcoholic liver disease for restoring the alcoholic's functional cognitive abilities, which, in turn, may improve the prognosis for psychosocial adjustment. PMID- 1758985 TI - Neuropsychological factors in individuals at high risk for alcoholism. AB - It has been postulated that deficits in certain areas of cognitive functioning among children of alcoholics may contribute to their increased risk for developing alcoholism and other substance abuse disorders. In this chapter, the recent evidence for this hypothesis is critically reviewed. Studies citing differences in cognitive functioning between persons at high risk versus those at low risk for alcoholism are presented as well as those studies that have failed to demonstrate differences in cognitive abilities. On balance, the evidence in support of variations in cognitive abilities at risk factors for the development of alcoholism is not strong. The equivocal nature of the literature may be due to a variety of issues related to the design of studies examining risk factors for alcoholism, to the variability of definitions of family history positive used, to the failure to adequately control potentially confounding subject variables, and to the improper analysis of data. Recommendations are made for future studies examining neuropsychological functioning in "at risk" samples. PMID- 1758986 TI - Vulnerability to cardiac disease. AB - Chronic consumption of ethanol has deleterious effects on the cardiovascular system, as manifested by an attenuation in myocardial contractility, a reduction in cardiac output, and the induction of arrhythmia. The arrhythmogenic effect of ethanol is associated with the high incidence of sudden death in alcoholics. Further, alcohol was found to potentiate arrhythmias due to nonpenetrating chest trauma, a finding of profound clinical significance. In addition, chronic ethanol consumption is closely linked to hypertension. Whether modest alcohol consumption may protect against coronary artery disease is controversial and not clearly established. Cessation of alcohol consumption occasionally results in reversal of ethanol-induced myocardial injury. However, the transition from ethanol-induced reversible injury to permanent heart damage is not well understood. Finally, the combined effects on the myocardium of alcohol and other abused drugs, such as cocaine and amphetamines, and the interaction of ethanol with chemicals such as nicotine, digitalis, and other medicaments are not well understood and may be fatal. PMID- 1758987 TI - Adult children of alcoholics. The history of a social movement and its impact on clinical theory and practice. AB - This chapter proposes that the popular social movement of adult children of alcoholics (ACOA) has had a profound impact on theory development and clinical practice in the fields of mental health and chemical dependence. The birth of the social movement is first traced, looking back to the origins of Alcoholics Anonymous in the self-help movement and the corresponding professional development of a systems perspective that included the notions of alcoholism as a "family disease" and the "alcoholic family," which included young children. Extending the idea to adults followed. This chapter examines why this movement could not originate in either professional field, accenting narrow theoretical base, oversimplification, professional denial, and bias in beliefs and values. Implications of the label ACOA are next addressed. Finally, a new integrated theory is proposed which bridges mental health, chemical dependence, and self help disciplines. This theory includes environmental, systems, and individual development perspectives and integration of behavioral, cognitive, and dynamic psychotherapies. The chapter concludes with new challenges for diagnosis and reimbursement. PMID- 1758988 TI - Epidemiological perspectives on children of alcoholics. AB - Because alcoholism is a highly heritable condition, children of alcoholics, especially sons, are at much higher risk than the general population for developing the disorder. Furthermore, secular trends are apparent for both sons and daughters of alcoholics, such that alcoholism has become more prevalent over time, increasing the morbid risk in offspring of alcoholics. Increases in prevalence of disorders known to be associated with alcoholism, such as conduct disorder, depression, and drug abuse, have also been found in younger cohorts, as well. At the genetic level, alcoholism appears to be heterogeneous, raising the possibility that alcoholism may be a product of numerous different kinds of gene environment interactions. Further advances in our understanding of alcoholism will come from molecular genetic studies and longitudinal studies of high-risk populations. PMID- 1758989 TI - Psychological characteristics of children of alcoholics. Overview of research methods and findings. AB - Recent years have witnessed a dramatic interest in the psychological characteristics of children of alcoholics (COAs). This chapter provides an overview of this research, focusing on (1) studies suggesting genetic contributions to the intergenerational transmission of alcoholism, (2) studies characterizing the features of an alcoholic rearing environment, and (3) empirical studies contrasting COAs and children of nonalcoholics (non-COAs). Although it appears that COAs do differ from non-COAs on a number of variables that might have etiological significance for the development of alcoholism, the pattern and consistency of findings defy a simple integration. Perhaps more important, much of the available research is characterized by methodological limitations that preclude strong inferences concerning the nature and extent of deficits in COAs. Relevant methodological issues such as ascertainment strategy, the heterogeneity of parental alcoholism, the specificity of COA deficits, and design strategies are described and their possible impact on study outcomes is discussed. PMID- 1758990 TI - From prevention to treatment. Issues for school-aged children of alcoholics. AB - Empirical and anecdotal evidence concerning the variables that mediate and moderate the relationship between parental alcoholism and child vulnerability has been used as the basis for a growing number of prevention and treatment programs for school-aged children of alcoholics. Common intervention foci include information on alcohol and alcoholism, the dynamics of alcoholic families, common social and emotional reactions (e.g., embarrassment, loneliness, guilt, depression, anger), skill building (e.g., problem solving, communication, expression of feelings), coping strategies for living in an alcoholic home, and general social and emotional support. The primary modality is a small group, which is usually time-limited. Groups are conducted in schools, community agencies, and mental health or drug treatment centers. Research on the effectiveness of several of these programs has yielded positive results with respect to a variety of psychosocial measures, although most studies share some common methodological shortcomings (e.g., lack of appropriate control groups, lack of longitudinal assessments of effects). More rigorous evaluation, as well as continued and expanded program development and outreach, is recommended. PMID- 1758991 TI - Treating adults raised by alcoholic parents. AB - The concept of adult children of alcoholics (ACOAs) is a recent one, yet ACOAs have had a formidable influence on the chemical dependence and mental health treatment field. Through their sponsorship of workshops and conferences, development of specialized inpatient and outpatient treatment programs, and generation of publications dedicated to understanding themselves with common interpersonal and intrapersonal problems, ACOAs have organized themselves into an influential social movement. Most ACOA treatment philosophies and programs are derived from the ACOA social movement using the concept of the "inner child" to guide the treatment. Unfortunately, few studies of treatment efficacy are available in the scientific literature. In this chapter, our discussion concentrates on the central treatment theme of the ACOA movement as it influences the treatment ideologies that currently guide ACOA treatment programs. We conclude by addressing the obvious need for research and the necessity for maintaining our ethical responsibility both in scientific inquiry and in the treatment of needy individuals. PMID- 1758992 TI - Potential biochemical markers for the predisposition toward alcoholism. AB - For over two decades, evidence has been accumulating that supports a genetic predisposition to alcoholism and the presence of subgroups among alcoholics. With this knowledge, searches are underway for biological markers, including biochemical trait markers, for predisposition to alcoholism. Most promising results to date have been obtained in studies on various enzyme activities in lymphocytes, platelets, and fibroblasts. Measurement of monoamine oxidase activity in platelets and adenylate cyclase activity in platelets and lymphocytes should enable rapid investigation of relatively large groups of subjects at high risk to become alcoholics. Such studies could generate a valid biochemical marker for vulnerability in alcoholism, which is not available at the present time. PMID- 1758993 TI - A longitudinal study of children of alcoholics. AB - This chapter reviews the identification, testing, and 8- to 12-year follow-up of 237 sons of alcoholic fathers and 237 controls (474 men). Subjects were selected from respondents to a questionnaire mailed to 18- to 25-year-old students and nonacademic staff at a university, with initial evaluations demonstrating few differences between sons of alcoholics and controls on quantity and frequency of drinking or many major life problems related to alcohol. The subset of 474 men actually tested in the laboratory also revealed few family history differences on personality attributes, including a lack of differential on the Type 1/Type 2 alcoholism scheme. Our laboratory has, however, consistently documented less intense responses to alcohol for the sons of alcoholics, findings consistent across subjective feelings, increases in body sway, and changes in several hormones and electrophysiological measures. This dampened response to ethanol for men at high future risk for alcoholism was not observed after challenges with two different doses of diazepam. PMID- 1758994 TI - Neurophysiological factors in individuals at risk for alcoholism. AB - The literature dealing with electrophysiological research in individuals at risk for alcoholism is reviewed. Event-related potential (ERP) and electroencephalographic (EEG) differences between family-history-positive (FHP) and family-history-negative (FHN) men have been reported both prior to the ingestion of alcohol and following alcohol challenge doses. At present, the most robust of these electrophysiological findings is the lower P3 amplitude of the ERP, which has now been replicated in several laboratories. This perhaps provides a phenotypic marker, distinguishing those at risk for alcoholism. However, its specificity for alcoholism and the role of gene-environment interactions in the development of alcoholism remain to be determined. PMID- 1758995 TI - Developmental behavior-genetic perspective of alcoholism etiology. AB - Gene-environment interactions underlying the etiology of alcoholism are amenable to investigation from a behavior-genetic perspective. The organismic characteristics that most frequently and reliably have been found to predispose to alcoholism are behavioral traits. Certain behavioral traits, viz., temperaments, have a substantial heritable contribution and comprise the elements from which complex habit patterns and personality traits develop. The unique interaction between the individual possessing certain extreme deviations in temperament traits with environmental contingencies occurring during the course of psychosocial development and throughout adulthood is hypothesized to determine the risk during any period of the lifespan for an alcoholism outcome. PMID- 1758996 TI - Basic animal research. AB - Recent research with animal models of the fetal alcohol syndrome has resulted in advances in the areas of prenatal and postnatal growth retardation, facial dysmorphology, immune system deficiencies, endocrine dysfunction, and central nervous system alterations, including behavior. The rat is the most common species used in these studies, although similar experimental changes have been produced in a limited number of studies in other species. The specific deleterious effects of ethanol on the fetus are dose-related and dependent on the stage of gestation, as with other fetotoxic agents. However, the precise timing and dose-effect curves have yet to be established for most types of ethanol induced damage. Various exposure regimens have been employed, including inhalation of ethanol vapor and intraperitoneal injection, as well as oral exposure by gavage, diet, or drinking water. In the early postnatal period, following gestational exposure, altered function is most marked, with recovery in some measurements with postnatal maturation. The present literature clearly defines developmental damage from gestational exposure to ethanol as well as areas for additional research. PMID- 1758997 TI - Genetic basis of atopy. PMID- 1758998 TI - Preventative therapy in adults with asthma. PMID- 1758999 TI - The dose-response slope: a useful method for expressing the results of methacholine provocation tests in healthy subjects? AB - In order to study the reproducibility of different indices of airway responsiveness, two bronchial provocations with increasing methacholine concentrations up to 256 mg ml-1 were performed within 2 weeks on 30 healthy volunteers. The dose-response slope [DRS = maximal fall (%) in pulmonary function/maximal non-cumulative methacholine dose (mumol)] was calculated from forced expiratory volume in 1 s (FEV1) and from area under the expiratory flow volume curve (AEFV). DRS reproducibility within 2 weeks in responsive (decline in FEV1 greater than 20%) and non-responsive subjects (decline in FEV1 less than 20%) was assessed. After log-transformation of the data the reproducibility was assessed with intraclass correlations (ICC) [with 95% confidence intervals (CIicc)], mean difference with limits of agreement (delta +/- SD), 95% confidence intervals for a single measurement (CIsm), and the absolute difference of the observations of the two days from each other (zero = ideal reproducibility). Provocative doses (PD20FEV1) could be calculated for 14 subjects on both occasions. In this responsive group the reproducibility of all the parameters used (PD20FEV1, DRSFEV1 and DRSAEFV) was high. In the non-responsive group, DRSFEV1 demonstrated a slightly, but not clearly, lower ICC than DRSAEFV. However, DRSFEV1 had clearly wider limits of agreement and CIsm than DRSAEFV. Also, with DRSFEV1 the observations of the two days differed significantly more from each other than with DRSAEFV (P less than 0.05). PMID- 1759000 TI - Reassessment of asthma management in an accident and emergency department. AB - To determine if shortcomings in asthma management in the Accident and Emergency (A & E) department identified in a previous (1983) study (Reed et al. Thorax 1985; 40: 897-902) had been corrected, we retrospectively reviewed the case records of patients attending with asthma between December 1987 and November 1988. There was an increase in the number of patients attending with asthma; 0.73 per 1000 in 1988 versus 0.57 per 1000 in 1983. Sixty-seven percent of patients were self-referred and 80% presented between 1600 h and 0800 h. There was inadequate recording of the asthma history and examination findings. Peak expiratory flow (PEF) was recorded in 86% before treatment (compared to 11% in 1983) and 70% after treatment. In addition, a prospective study of 40 patients responding to a questionnaire 2 weeks after discharge, revealed persistent symptoms of unstable asthma in 50%. Although there has been a marked improvement in the use of PEF measurements since the 1983 study, the standards of management of asthma patients may still be inadequate as evidence by the presence of unstable asthma symptoms in many of those discharged. A standardized management protocol which provides guidelines for treatment based on PEF has been introduced to the A & E department. PMID- 1759001 TI - A 2-year longitudinal study of lung hyperinflation in young asthmatics. AB - Functional residual capacity (FRC) was measured at 6-monthly intervals for at least 2 years in 42 young asthmatic children. Over the 2-year period FRC decreased in the 42 children from a median of 136% to 117% of that predicted for height (P less than 0.05). These changes in FRC were associated with a reduction in the number of children receiving no regular treatment (ten at recruitment, 0 at 2 years), P less than 0.05, and an increase in the number of children receiving inhaled steroids (ten at recruitment and 29 at 2 years), P less than 0.01. Twenty-five children were hyperinflated at recruitment (FRC greater than 120% of that predicted for height) with median FRC 152% compared to only 16 children at 2 years median FRC 117%, P less than 0.01. We conclude that FRC decreases as asthmatic children get older but some children, worryingly and despite increased use of prophylactic therapy, remain chronically overdistended which may put them at serious risk of chronic obstructive airways disease in later life. PMID- 1759002 TI - Differences in tonsil core bacteriology in adults and children: a prospective study of 262 patients. AB - The tonsillar microflora of 262 patients with recurrent acute tonsillitis studied in 1989-1990 is presented. The patient population was divided into three age groups to determine any age-related features. One-hundred and forty-nine patients (57%) were in the 2-7-year-old group, 72 (28%) the 8-14-year-old age group, and the remaining 41 (15%) were over 15 years of age. H. influenzae was the single most common bacterium isolated from the centre of the tonsil (referred to as 'tonsil core'), and this was more prevalent in the 2-7-year-old age group. Staph aureus was the next most commonly isolated bacterium and was most frequently seen in the 8-14-year-old age group (29%). Anaerobic bacteriology was performed in 120 patients. Strict anaerobic species were isolated in significant numbers from the tonsil core in 5% but were present in the superficial culture in all. Anaerobes were present in moderate to heavy numbers in 32% of superficial swabs overall and this was more frequently seen in the older age groups. Mixed pathogens were found throughout all age groups and were most prevalent in the 8-14-year-old age group at 46%. The commonest mixture was H. influenzae and Staph aureus. Normal flora only was commonly found in the superficial swab and rarely in the tonsil core. The number of specimens containing a beta-lactamase producer was assessed for each group; this was similar in all of the groups ranging from 43% in the 2-7 year-old group and 53% in the 8-14-year-old group to 39% in the greater than 15 year-old group. PMID- 1759003 TI - Cystic fibrosis: what do patients know, and what else would they like to know? AB - As the survival of patients with cystic fibrosis (CF) improves, it becomes increasingly important to address such issues as employment, reproduction, and quality of life in adulthood. In this study, 22 patients and 20 parents completed a questionnaire about the natural history, treatment and genetics of cystic fibrosis. Patients and parents knew as much as each other about the natural history of cystic fibrosis. Patients under 13 knew significantly less about the genetics and treatment. All found probability questions about heredity difficult. All the patients indicated that they would like further information on the future and how they would cope, through CF literature, organized patient groups and, in adolescence, would prefer to obtain information from medical staff rather than parents. Patients had received considerable information about the disease and its treatment from parents and clinical staff, but few had discussed the day to day problems of living with cystic fibrosis. This study has identified specific areas of ignorance in patients with cystic fibrosis, areas that need addressing in view of the improved survival associated with this disease. PMID- 1759004 TI - The effect of a beta 2-adrenergic agonist and a histamine H1-receptor antagonist on the late asthmatic response to inhaled antigen. AB - In this double-blind, randomized, cross-over trial, the role of histamine and the possible protective effect of a beta 2-adrenergic agonist in the later asthmatic response to inhaled antigen was investigated in nine atopic asthmatic patients. On four study days, 2-4 weeks apart, patients were given either: placebo; salbutamol aerosol 400 micrograms before and 200 micrograms 2-hourly after challenge; oral terfenadine 120 mg 2 h before and 10 h after challenge; and, on the final day, lung function was monitored without medication or antigen challenge. A nebuliser-dosimeter system was used to deliver a predetermined, single dose of antigen aerosol. Response was assessed by specific airways conductance (SGAW) measured in a body plethysmograph; FEV1 and PEFR were measured with a Pocket Spirometer. All measurements were made for 10 h in the clinic and then the patients continued to record PEFR and FEV1 at home for at least 2 more hours. Similar findings were obtained with all three lung function parameters. After challenge, the early response (ER) was small when compared with the late response (LR). All patients had a definite LR on the placebo day when FEV1 was compared with 'no challenge day'. Neither drugs had much effect on the small ER. The LR was not altered by terfenadine but was very significantly attenuated by salbutamol; the mean maximum fall in FEV1 during LR being 31, 29 and 12% after placebo, terfenadine and salbutamol, respectively. It is unlikely that histamine plays an important role in the LR to inhaled antigen but beta 2-adrenergic stimulants can attenuate LR, probably by directly preventing bronchial smooth muscle constriction and also by stabilising bronchial mast cells. PMID- 1759005 TI - Salbutamol plus beclomethasone dipropionate, but not salbutamol alone, completely prevent early and late asthmatic responses to allergen. AB - The effect of a week treatment with inhaled salbutamol plus placebo (S+P) vs. salbutamol combined with beclomethasone dipropionate (S+BDP) on early and late asthmatic responses to inhaled allergen was studied in ten atopic patients in a randomized, double-blind, cross-over study. All patients had previously shown a dual type response to the specific bronchial provocative test (sBPT). Each patient performed two periods of treatment for a week, with a 15 day interval between them: (a) salbutamol 0.3 mg, tid + placebo; (b) salbutamol 0.3 mg+BDP 0.2 mg, tid; at the end of each treatment period, sBPT was performed and the last treatments were given 1.5-2 h before and 3-4 h after allergen challenge. S + BDP completely prevented both early and late responses to allergen, while S + P reduced but did not completely inhibit early and late responses. The difference between the two treatments was significant for early and late asthmatic responses. Non-specific bronchial hyperresponsiveness to methacholine was performed before each treatment period, after 6 days of treatment before sBPT and the day after sBPT at the end of the treatment period; there was only a mild increase in PD15FEV1 methacholine after 6 days of treatment with S + BDP in comparison with S + P treatment. These results suggest that salbutamol plus beclomethasone may be used effectively in the prophylaxis of early and late asthmatic reactions induced by allergen in sensitized subjects. PMID- 1759006 TI - Portable oxygen therapy: assessment and usage. AB - Fifty portable oxygen assessments, based on 6-min walking tests, were reviewed to produce guidelines for assessment and prescription of portable oxygen, and to evaluate factors predicting benefit. Patients with a portable cylinder were questioned about benefits/difficulties and usage of portable oxygen. A significant improvement on the oxygen compared to the air walk was found (median 9.7%) which correlated with the oxygen desaturation on the baseline walk (r = 0.51, P less than 0.05). A placebo effect was demonstrated using an air cylinder (median improvement 6.1%). There was no correlation between improvement in walking distance and decrease in visual analogue scale (VAS) score of breathlessness. We recommend standard portable oxygen assessments based on a series of 6-min walks. Improvements of 10% in walking distance or VAS score from the oxygen to the air walk would lead to the patient being offered a portable oxygen cylinder. PMID- 1759007 TI - Cardio-respiratory responses to exercise following treatment of acute severe asthma. AB - Asthmatic patients are encouraged to adopt a normal and active life-style. However, following treatment of acute severe asthma, patients may ask for advice about taking exercise. Serial measurements of the cardio-respiratory responses to continuous work load exercise, were made in asthmatic patients convalescing following hospital treatment of an acute exacerbation. Eighteen asymptomatic patients, (seven male) aged 18-48 years, were studied. The first test was performed within 1 week of admission, when the mean (SD) peak expiratory flow rate (PEFR) was 88 (20)% predicted normal and the arterial oxygen tension (PaO2) was 13.1 (1.4) kPa. No significant differences in the mean cardio-respiratory responses, from the last minute of exercise, were found during the 4-week study. There were no significant differences in the four tests, between the resting PEFR, lowest post-exercise PEFR or % change in PEFR. Also, there were no significant differences in the pre-exercise, end of exercise and recovery (10 min after exercise) PaO2, between the four tests. However, taking the four tests as a whole, significant relationships were found between the recovery PaO2 and the lowest post-exercise PEFR, expressed in absolute terms (r = 0.515, P less than 0.001), and as a percentage of predicted normal (r = 0.533, P less than 0.001); and also between the recovery PaO2 and the % change in PEFR after exercise (r = 0.299, P less than 0.05). It is suggested that a formal exercise test should be performed in convalescent asthmatics wishing to participate in active sports. Patients with exercise-induced asthma may then be identified and treated appropriately. PMID- 1759008 TI - Audit of tuberculosis contact tracing procedures in south Gwent. AB - A survey of part of the work of the tuberculosis contact clinic over a 5-yr period (1984-1988 inclusive) is presented. There were 106 notified index cases and 781 contacts were screened. Following chest radiography, Mantoux tests and BCG vaccinations, only four contacts who were tuberculin-positive required chemoprophylaxis. One asymptomatic adult casual contact was treated as an active case because of shadowing on a chest radiograph. Two other cases of active tuberculosis came to light but not through the routine contact tracing procedures. All cases given treatment were contacts of a single index case and the family case history is described. Because of experience with this family the contact tracing procedures will continue locally but will be monitored prospectively. In view of different findings in other centres it is suggested a further national survey is indicated with special attention to regional variations. PMID- 1759009 TI - Endobronchial sarcoidosis presenting as severe upper airways narrowing with normal chest radiograph. PMID- 1759010 TI - Pneumopyopericardium in a Zimbabwean man with Klebsiella pneumonia. PMID- 1759011 TI - Occult respiratory failure as a cause of neuropsychiatric symptoms in chest wall deformity and neuromuscular disease. PMID- 1759012 TI - Giant cell tumour of rib: a case report. PMID- 1759013 TI - Evaluation of chest percussion in the treatment of patients with copious sputum production. PMID- 1759014 TI - Primary pulmonary hypertension and thromboembolic pulmonary hypertension- similarities and differences. PMID- 1759015 TI - The Living with Asthma Questionnaire. AB - The 'Living with Asthma Questionnaire' is an asthma-specific quality of life scale for assessing patients' own subjective experiences of asthma. The purpose of the questionnaire is to assist individual patient management and to provide an outcome measure for use in clinical trials. The scale has 68 items and covers 11 domains of asthma experience which were derived from focus group discussions amongst asthma sufferers. The initial item set was refined through standard psychometric techniques using a total of 783 patients and there is no statistical evidence for independent, domain-specific subscales. Validation studies are described. PMID- 1759016 TI - Measuring functional status in chronic lung disease: conclusions from a randomized control trial. AB - The optimal method of assessing the effect of treatment on the day-to-day function of patients with chronic airflow limitation has not yet been established. Therefore, we examined the performance of the 6-min walk test, a rating of dyspnea following the walk test, and three different questionnaires measuring dyspnea in daily activities, in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primary fixed chronic airflow limitation. Clinically important and statistically significant effects of salbutamol and theophylline on dyspnea during the day-to-day activities were detected by each measure, but the Chronic Respiratory Questionnaire (CRQ) was more powerful than the other questionnaires, either the Oxygen Cost Diagram or the Medical Research Council Dyspnea Questionnaire as modified by the Rand Corporation. Changes in the CRQ dyspnea score showed a higher correlation with changes in spirometry, walk test score, dyspnea following the walk test, and global ratings of dyspnea than did the other two measures. We conclude that the CRQ is a responsive, valid measure of functional status for clinical trials in chronic lung disease. PMID- 1759017 TI - Experience of using the CRQ (Chronic Respiratory Questionnaire). AB - We have examined the role of the Chronic Respiratory Questionnaire in practice. The questionnaire covers aspects of disability in patients with chronic lung disease in terms of dyspnoea, fatigue, emotional function and mastery. It therefore provides a measure of physical disability and quality of life in patients with lung disease. The questionnaire was validated in older patients with chronic obstructive lung disease and is particularly responsive to changes within an individual. Its major disadvantages include the lack of sensitivity in patients with minor symptoms or possibly those in a younger age group and that it is also not possible to make comparisons between populations with the CRQ. It is, however, particularly good at demonstrating changes in disability in older patients with chronic airways disease. PMID- 1759018 TI - The St George's Respiratory Questionnaire. AB - The St George's Respiratory Questionnaire is a standardized self-completed questionnaire for measuring impaired health and perceived well-being ('quality of life') in airways disease. It has been designed to allow comparative measurements of health between patient populations and quantify changes in health following therapy. The background and rationale for its development are discussed together with an analysis of its performance. PMID- 1759019 TI - The role of health economics in clinical decision-making: is it ethical? AB - With health care resources inevitably limited, we must ensure that they are used where they will do the most good. Doing good means improving people's life expectancy and quality of life, two characteristics which are combined in the Quality-Adjusted-Life-Year, or QALY. Even with effectiveness measured in this humanitarian way some people think it is unethical to let cost-effectiveness notions guide health care priorities. But costs represent sacrifices of health imposed on others, and it cannot be ethical to ignore such sacrifices. Indeed the reverse is true, it is unethical to ignore costs, and not to seek to become more efficient. PMID- 1759020 TI - Economic evaluation studies in respiratory medicine. AB - The need for efficient use of resources in the provision of health care is now an accepted reality. Despite its economic significance, respiratory disease has been the subject of very few examples of the application of techniques of economic evaluation. There are a number of examples of cost-minimization studies, and these serve to emphasize that choices based on drug acquisition costs may be quite different from those based on the total costs of care. The difficulty of defining uni-dimensional measures of health outcome for respiratory disease has hampered the development of cost-effectiveness studies, and the future of these must lie with the efforts to develop measures of quality of life more appropriate to this area of medicine. But the multi-dimensional nature of relevant health outcomes suggests that cost-utility approaches are likely to play an important future role, as off attempts to directly establish patients' monetary valuations of the health benefits offered by new respiratory medicines. PMID- 1759021 TI - Audit in respiratory disease. AB - Respiratory medical audit is discussed in terms of Structure, Process and Outcome with a description of the audit Feedback Loop of monitoring, assessment, improvement followed by further monitoring and assessment. Methods of monitoring include sentinel case, criterion-based, small group comparison, surveys and peer review. There are professional, social and pragmatic reasons for audit which is the responsibility of the provider professionals and requires adequate resources. PMID- 1759022 TI - The patient's viewpoint. PMID- 1759023 TI - [Parathyroid function in hypertrophic myocardiopathy]. AB - It has been suggested that hypertrophic cardiomyopathy (HCM) may be associated with hyperparathyroidism. We evaluated parathyroid function in 15 patients with HCM and 14 patients with primary dilated cardiomyopathy (DCM), measuring different parameters of calcium metabolism (total serum calcium, ionized calcium, PTH, vitamin D metabolites, alkaline phosphatase, osteocalcin). As a group PTH levels were normal in HCM (intact PTH 3.9 +/- 1.6 pmol/l, midmolecular PTH 59 +/- 13 pmol/l and carboxyterminal PTH 0.6 +/- 0.4 ng/ml), but in 3 patients carboxyterminal PTH levels were persistently higher than normal, while all other parameters of calcium metabolism were normal. We conclude that parathyroid function is normal in patients with HCM, although some of them may have an abnormal secretion and/or metabolism of carboxyterminal PTH fragments, or a circulating substance the interferes with this PTH assay. Parathyroid function in DCM patients was normal, except in a patient who had hyperparathyroidism secondary to vitamin D deficiency. PMID- 1759024 TI - [The efficacy of propafenone in preventing recurrent auricular fibrillation and flutter]. AB - In order to investigate the efficacy of propafenone in the prevention of paroxysmal flutter or fibrillation, we treated 21 patients without left ventricular disfunction. Age was 60 +/- 14 (mean +/- sd) years, left atrial diameter by echocardiography 37 +/- 7 mm, cardiothoracic index 0.48 +/- 0.05 (0.41-0.57) and P wave duration 100 +/- 17 ms. The frequency of recurrences before treatment was: daily in five (23%), weekly or more in eight (38%), monthly weekly in seven (33%) and quarterly-monthly in one (5%). Propafenone (671 +/- 187 mg/24 h) was given after recurrences were demonstrated under treatment with 1-3 antiarrhythmic drugs per patient. During 8.9 +/- 3.5 months of follow-up (range 6 19) 5 patients (23%) were completely free of recurrences; in seven (33%) the incidence decreased by greater than 50% with a marked decrease in duration. Side effects appeared in 12 cases (57%), leading to its discontinuation in four (19%). Arrhythmogenic effects were observed in 2 cases (9%). Propafenone is effective in greater than 50% of patients with paroxysmal atrial flutter or fibrillation, resistant to other antiarrhythmic agents. The incidence of side effects is high, but they are usually not severe and reversible. PMID- 1759025 TI - [Ambulatory transesophageal echocardiography: 2 years of experience]. AB - In this report we study the value of ambulatory transesophageal echocardiography (TEE) in the clinical setting after a 2-year experience at our department. Since December 1988 until February 1991, 470 TEE examinations were indicated in 430 patients. Excluded were 8 cases, two out of them due to a formal contraindication and six who did not tolerate the procedure. The clinical indications for the examination, in the 462 studies performed, were as follows: possible cardiac source of emboli in 165 (35%); native mitral valve disease in 91 (20%); prosthetic valve dysfunction in 54 (12%); diseases of the aorta in 44 (10%); suspected infective endocarditis in 41 (9%); study of left ventricular function in 26 (6%); congenital heart disease in 18 (4%); tumor or intracardiac mass in 11 (2%); miscellaneous in 12 (2%). Based on this experience, we can conclude that TEE is a clinically useful technique for: 1) the study of mitral regurgitation, either native or prosthetic; 2) the detection of vegetations and abscesses in infective endocarditis; 3) the evaluation of a possible cardiac source of emboli; 4) the examination of the aorta in cases of suspected dissection; 5) the completion of the anatomic study in some congenital heart diseases, particularly after a surgical correction; 6) the study of patients with a technically inadequate transthoracic approach. PMID- 1759026 TI - [Coronary angioplasty with a rotary atherotome]. AB - Several new coronary dilatation systems, including those using laser energy, atherectomy devices and stent implantation, are being developed as alternative or complementary procedures to coronary artery balloon angioplasty. We report our initial experience performing coronary angioplasty with a new rotational atherectomy device, the transluminal extraction catheter, which simultaneously cut and aspirate fragments from the atherosclerotic plaque. The components of the whole system are a special guidewire to cross the stenosis, the atherectomy catheter and the conduction-control unit. This unit, connected when the atherectomy catheter is positioned across the lesion, produces rotation of the conical bladder located in the catheter distal tip and simultaneous aspiration of residual particles. The procedure was performed in 11 patients in whom 13 lesions were dilated. All patients were male (mean age 55 +/- 23 years, range 45-77). The reason for the angioplasty was stable angina in 2 patients and unstable angina in the remaining seven. Initial success (residual stenosis less than 50% of vessel diameter) was obtained in 10 of 13 lesions. In two, conventional balloon angioplasty was required to improve atherectomy result. The only unsuccessful procedure was in a proximal right coronary artery venous graft, in which a large dissection occurred. Patient had angina but no myocardial infarction. Pathologic examination of aspirated material revealed fibrous tissue in 12 cases and cholesterol crystals in four. We conclude, with the limitation of a preliminary study, that rotational atherectomy with the transluminal extraction catheter is a useful procedure to relief coronary stenosis of the coronary arteries. PMID- 1759027 TI - [The surgical treatment of aneurysms of the ascending aorta with associated aortic insufficiency. Total replacement with reimplantation of the coronary arteries]. AB - We reviewed our experience with replacement of the ascending aorta and aortic valve with a composite graft and reimplantation of coronary arteries to the tube graft during 8 years interval from April, 1982, to April 1990. 24 patients underwent repair, the mean age was 49.83 years. Annuloaortic ectasia was the most common indication (58.33%), followed by aortic dissection (acute or chronic). Emergency operation was carried out in nine patients with aortic dissection (37.5%) and elective in 15. The mean duration of cardiopulmonary bypass was 118 +/- 4 minutes and of aortic clamping 83.85 +/- 2 minutes. Hospital mortality was 4.17%, reoperation for hemorrhage was 12.5% and perioperative morbidity for other causes was 34.7%. There were one late death. 20 patients were follow-up with a total of 638 patients-months (two patients excluded with insufficient follow-up and one late death). At last follow-up 14 patients were in functional class I. Eight year actuarial survival for the 24 patients was 91%. We believe that replacement of the ascending aorta and aortic valve with a composite graft and coronary arteries reimplantation to the tube graft is more than one satisfactory alternative to supracoronary graft replacement and aortic valve replacement. It offers the advantage of excluding all abnormal aortic tissue, eliminating the risk for later development of complications in the non excluded disease aorta. It supposes the method of choice for patients with anuloaortic-ectasia, aneurysms of the sinuses of Valsalva with aortic insufficiency, and aortic dissection with proximal affectation of coronary arteries and aortic valve. PMID- 1759028 TI - [Chronic heart failure (I). The epidemiology of chronic heart failure]. PMID- 1759029 TI - [Brucellar pericarditis: 2 different forms of presentation for an unusual etiology]. AB - Two cases of Brucella melitensis pericarditis are reported. Pericardial involvement was the first and almost only manifestation of brucellosis in the first patient while in the second, a significant pericardial effusion was discovered on a routine echocardiogram performed in a patient with clinically florid brucellosis. Some etiopathogenic aspects of this uncommon etiology are discussed. PMID- 1759030 TI - [Severe hypoxemia due to a right-left shunt at the level of the foramen ovale. A complication of right ventricular infarct]. AB - A 76-year-old woman with an inferior wall myocardial infarction, with right ventricular involvement, developed severe arterial hypoxemia with neurological involvement. Pulmonary edema or embolism and chronic obstructive pulmonary disease were ruled-out, and a right-to-left shunt was demonstrated by contrast echocardiography at the level of the foramen ovale. After inotropic support and oxygen supplementation, the patient recovered, although with significant neurological sequelae. No focal lesions were detected in the central nervous system by computerized tomography. Hypoxemia improved, coinciding with the disappearance of right-to-left shunt by contrast echocardiography. PMID- 1759031 TI - [The 2-dimensional and Doppler color echocardiographic study of a congenital aneurysm of the sinus of Valsalva with a fistula of the right atrium in an adult]. AB - This report describe a 69-year old woman with a congenital aneurysm of the non coronary sinus of Valsalva ruptured in the right atrium, causing severe hemodynamic derangement of the right ventricle. The site of the communication between the aneurysm and the receiving chamber was accurately diagnosed by two dimensional color flow Doppler imaging which provided more valuable preoperative information than conventional aortography. PMID- 1759032 TI - [A superior vena cava syndrome secondary to intracavitary pacemakers. The diagnostic and therapeutic aspects]. AB - Two cases of superior vena cava syndrome secondary to an endocardial pacemaker are reported. We discuss diagnosis methods and we point out the use of radioisotope cavography in patients with iodate contrast allergy. We suggest early administration of thrombolytic therapy besides of anticoagulants and we review the literature of previous observation of venous occlusion. PMID- 1759033 TI - Comparison between computed tomography and magnetic resonance imaging in the postoperative evaluation of acromegalic patients. AB - Twelve acromegalic patients who underwent transphenoidal resection of a GH secreting pituitary adenoma were evaluated postoperatively by Computed Tomography (CT) and Magnetic Resonance (MR). CT and MR findings were compared with surgical and clinical results. MR was more accurate than CT in delineating postoperative abnormalities of the infundibulum, diaphragma sellae and optic chiasm. In three cases MR differentiated packing materials from adenomatous tissue. In cases with biochemical evidence of residual or recurrent tumor, MR clearly demonstrated intra- or extrasellar adenomatous tissue and the spatial relationship between the soft tissue mass and the cavernous sinuses. CT was superior to MR only in demonstrating sellar floor disruption. MR imaging detected the anatomical causes of clinical abnormalities in almost all acromegalic patients with incomplete recovery after surgery. On the basis of MR results it is possible to plan additional surgery, radiation therapy or medical treatment. MR may be the radiological procedure of choice for both surgical treatment planning and postoperative follow-up. PMID- 1759034 TI - GH response to GH-releasing factor in dementia and its relation with TSH response to TSH-releasing factor. AB - We have studied the GH response to GH-releasing factor (GRF) and the TSH response to TSH-releasing factor (TRH) in two groups or patients with dementia. A group of 28 patients with Alzheimer's disease (AD) and another group of 28 patients with dementia of vascular origin (VD). The GH response to GRF exhibited no difference between AD and VD patients (12.2 +/- 10.85 micrograms/L vs. 9.96 +/- 9.9) and there was no correlation with GH response to GRF and sex, stage of the disease and cerebral atrophy. The number of cases with exaggerated, normal or without response were similar in AD or VD patients. The TSH response to TRH exhibited no difference between AD and VD patients (9.18 +/- 4.93 mU/ml vs. 10.35 +/- 8.81). There was no correlation with TSH response to TRH and sex, stage of the disease, cerebral atrophy and response of GH to GRF. The number of cases with exaggerated, normal or without response was similar in AD or VD patients. PMID- 1759035 TI - [The measurement of bronchial hyperreactivity for military service fitness]. AB - The authors discuss the efficacy of methacholine challenge to discriminate fit subjects to military service. We evaluated the relation between bronchial hyperreactivity and clinical symptoms, airways caliber and atopic status in a group of italian conscripts who reported to have bronchial asthma. Five-hundred four subjects were studied. Bronchial hyperreactivity was measured by methacholine test, and atopic status was assessed by skin-tests. A measurable PC20 FEV1 was detected in 424 subjects. On the basis of the methacholine threshold concentration the overall sample was divided in four categories. The four categories differed as regards onset of disease, lung function and skin reactivity towards Dermatophagoides Pter, whereas no difference was found as regards skin reactivity towards Grass. In the group evaluated in spring, the four categories differed as regards skin reactivity towards Grass. In conclusion we found that bronchial hyperreactivity is related to clinical history, lung function and atopic status; the measurement of bronchial hyperreactivity is important to evaluate conscripts referring bronchial asthma. PMID- 1759036 TI - [Osteolysis in an aged woman with recurrent urinary infections]. AB - Hematogenous osteomyelitis has two incidence peaks; the first in childhood, the second in elderly people. The vertebrae are frequently involved in the case of elderly people and the diagnosis is difficult to make in as much as the radiological control of osteolysis is often attributed to malignant metastasis. The Authors describe a case of vertebral osteolysis in an elderly woman with relapsing urinary infections. The clinical history of the patient is described and the diagnostic procedure is critically discussed. In this way the diagnosis of osteomyelitis of the thorax-lumbar tract is reached. The Authors go on to consider the possibility of an infectious genesis of isolated osteolytic lesions, especially in patients with risk factors and ones prone to certain conditions such as urinary infections, above all because the complications of osteomyelitis can be extremely serious. PMID- 1759037 TI - Septic polyarthritis in chronic tophaceous gout. AB - This paper reports the case of a 48 year old patient with chronic tophaceous gout who was admitted to the hospital with a pneumococcal polyarthritis affecting the same joints previously involved by gout attacks. The authors emphasize that the possibility of a septic arthritis should always be considered in the gouty patient, and not only in the elderly, as stressed in the literature, but also in younger patients. PMID- 1759038 TI - [Extramedullary plasmocytoma. Description of 2 cases with localization in the vocal cords]. AB - The authors describe two cases of extramedullary plasmacytoma with localization to the vocal cord. They underline: the rarity of the laryngeal involvement, the different histogenetic, prognostical and therapeutical aspects as regards solitary plasmacytoma and the peculiarity of the second case where after 15 years the extramedullary plasmacytoma recurred in the same field without any systemic spread. PMID- 1759039 TI - [Ridogrel, a new platelet antiaggregant molecule with a double mechanism of action. A pharmacological and clinical profile]. AB - Ridogrel has a double mechanism of action: it is a combined thromboxane A2 synthetase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor blocker, demonstrated in vitro, as well as in vivo in animals and in man. In man, ridogrel is quickly absorbed after oral administration (30-60 min). The half-life is about 6-9 hours. At the oral dose of 300 mg b.i.d., the steady state has been reached at the third day of administration. Pharmacodynamic studies in healthy volunteers as well as in patients demonstrate a marked decrease in TXB2 serum level and an increase in 6ketoPGF1 alpha level. Moreover ridogrel inhibits the human platelet aggregation induced by U46619, collagen and arachidonic acid (thromboxane A2/prostaglandin endoperoxide receptor blocker). During the ridogrel treatment there have been neither variations of coagulative parameters (PTT, APTT, plasmatic fibrinogen) nor variations of other metabolic parameters except for those concerning the antiaggregant activity. To conclude, the preliminary data on about 100 healthy volunteers and more than 100 patients show that pharmacologic combined actions on enzyme and on receptors could be more efficacious than one single activity in eliminating circulatory flux resistance, in potentiating thrombolysis and in preventing or postponing vessels reocclusions. According to the above-mentioned results, ridogrel could have a good application in correction of thrombotic disorders due to platelet activation. PMID- 1759040 TI - [Rheumatic fever, the idea of progress and the circularity of time]. AB - Rheumatic fever, once virtually "gone" from the western world, has made a come back in the mid nineteen-eighties. This is disturbing because the control of rheumatic fever was a source of pride to the medical community. Changes in medical practice, such as a less compulsive attitude vis-a-vis streptococcal infections, and social changes, such as "house starvation", probably conspired to bring about the come-back. It's likely that the emergence of more virulent and more rheumatogenic streptococcal strains was facilitated by these changes. Physicians should once again be alert to the streptococcal threat, and accurately diagnose and effectively treat streptococcal pharyngitis. PMID- 1759041 TI - [Criteria of radicality in surgical therapy of rectal cancer]. AB - The Authors discuss on their experience in radical rectal cancer surgery critically reviewing results of the current literature. In particular, the importance of distal clearance, abdominopelvic lymphadenectomy and total excision of the mesorectum is stressed. They conclude that radical surgery, if performed according to certain principles, can improve survival without affecting the incidence of major complications. PMID- 1759042 TI - The clinical features, course, prognosis and treatment of juvenile arthritis. AB - The author's classification of juvenile arthritis (JA) differs from most by utilizing both the type of onset and the disease course separated into individual subgroups. The clinical aspects of each are described in detail, along with the special tests and studies to be done to differentiate them. Particular attention is given to the differences between the four subgroups of the pauciarticular onset group. There are different genetic factors for each subgroup and new data on HLA typing utilizing DNA techniques may be helpful in the prognosis of the disease course. The therapy of JA begins with non-steroidal anti-inflammatory drugs, continues with second-line drugs such as gold and penicillamine, and finally leads to the use of immunosuppressive agents. The range of doses, the maximal dose, and the frequency of administration is given for each medication. The long-term prognosis is generally good, with a low death rate, primarily seen in the systemic onset patients. The causes of death vary around the world. Prognosis for continued joint activity and joint function is determined significantly by the type of onset and is worse in the rheumatoid factor positive polyarticular onset group. PMID- 1759043 TI - [Immunological implications of surgical intervention in critical and noncritical patients]. AB - Immunological implications are important in every surgical operation, specially when it is necessary to remove the spleen. She plays an important role in immunological aspecific (filter, phagocytosis) and specific processes (production of IgM and regulation of T- and B-lymphocytic system). Splenectomy causes an immunodeficiency with frequent post-operative complications (the most important is OPSI). Each operated patient is considered generically immunodeficient because surgical trauma and anesthesiologic practice are at the base of immunological alterations (biological barriers, aspecific immunity, A.P.P., complement, specific immunity, NK cells). It's indispensable to know pathological situations that make "critical" the immunological state: caloric-proteic malnutrition, elderly (greater than 70 years old), immunosuppressive therapy, sepsis, shock, neoplasms. I. e.: a patient about seventy years old presents a reduced endocrine secretion of thymic hormone and, probably, a low synthesis of immunoglobulins. Besides the corticosteroids modify the answer of T-lymphocytes and NK cells. Sepsis induces metabolic and immunological alterations after early activation of humoral mediators, modified quantity and life of A.P.P., activation of complement, inhibition of cell-mediate immunity, modification of number and activity of haematic lymphocytes. Trauma induces a hypersecretion of corticosteroid, adrenalin, noradrenaline, glucagon with consequent hypercatabolism that causes malnutrition. The hormonal hypersecretion is a determining factor of reduced phagocytic activity (inhibited migration of neutrophils and monocytes), quantitative and qualitative alterations of complement, deficit of T-cells, hyporeactivity to skin test, depressed answer of antibodies to bacterial and viral antigens. Progressive neoplasms are characterized by modification of T-lymphocytes number, depressed macrophagic activity, hyporeactivity to skin tests. PMID- 1759044 TI - Long-term effects of ovariectomy on pituitary-adrenal axis and specific antibody response in rats. AB - The effects of ovariectomy on morphologically demonstrable characteristics of lymphoid tissue, pituitary, and adrenal glands as well as on plasma ACTH and corticosterone levels and humoral immunity of female Lewis rats were investigated. The present study establishes ovaries as potential regulatory organs upon thymus, pituitary, and adrenal glands in female Lewis rats. In addition to the effects on these important lymphoid organs and endocrine glands, ovariectomy influenced the time course of serum IgM antibody titres against fluorescein isothiocyanate (FITC), but had only moderate effects upon serum IgG antibody titres. In conclusion, the present results suggest that ovariectomy modifies morphological characteristics of the thymus and pituitary-adrenal axis. Furthermore, circulating corticosterone seems to play an important role in regulating antibody formation in intact compared to ovariectomized female Lewis rats, while the influence of thymic mass is far from clear. PMID- 1759045 TI - Use of an artificial oxygen carrier in isolated rat liver perfusion: first demonstration of net glucose uptake at physiological portal glucose concentrations using a hemoglobin-free perfusate. AB - A defect in isolated perfused rat-liver (IPRL) preparations has been proposed to explain discrepancies between in vivo and in vitro findings regarding hepatic glucose metabolism. The aim of the present study was to investigate whether a preparation of IPRL using a synthetic hemoglobin-free perfusate was capable of net glucose uptake and glycogen deposition at physiological portal substrate concentrations. Livers from fed anaesthetized rats were perfused in a recirculating system using a fluorocarbon emulsion as artificial oxygen carrier. Depending on the prevailing glucose concentration, livers exhibited net glucose uptake or release with a threshold value of 5.5-6.0 mM glucose. Net glucose uptake was associated with net glycogen deposition (+0.23 to +0.59 mumol C6 min-1 g-1). From 5.8 mM (n = 3) and 10.0 mM (n = 8), initial concentration glucose levels fell to 5.3 +/- 0.2 mM after 210 min (n = 3) and 6.3 +/- 0.9 mM after 120 min (n = 8), respectively. This was equivalent to a net glucose uptake of -0.16 and -0.45 mumol min-1 g-1. Anoxia reversibly switched hepatic glucose balance from net uptake (-0.42 mumol min-1 g-1) to release (+0.69 mumol min-1 g-1) followed by net uptake (-0.50 mumol min-1 g-1) after reinstitution of aerobic conditions. We conclude that the composition of perfusion media might play a pivotal role for studies of glucose metabolism in the isolated perfused rat liver. In our experimental model, using a hemoglobin-free synthetic medium, net glucose uptake was readily demonstrated at physiological portal substrate concentrations similar to the in vivo situation. PMID- 1759046 TI - Effects of dexamethasone on glutamine metabolism in the isolated vascularly perfused rat small intestine. AB - Post-stress metabolism is associated with a large glutamine (Gln) efflux from muscle and an increased Gln utilization by the small intestine. Both appear to be modulated by corticosteroids. The present investigation was performed to better characterize the mechanism of corticoid action on Gln metabolism in an isolated preparation of vascularly perfused rat small intestine. In all perfusions, a synthetic perfusate free from blood components was used with only 0.6 mM Gln and 10 mM glucose as substrates. Irrespective of dexamethasone concentrations in the vascular perfusate (none, 0.25 mg l-1, or 2.5 mg l-1, isolated intestines from normal rats exhibited unchanged extraction rates of Gln (-85 +/- 8, -89 +/- 10, and -87 +/- 16 nmol min-1 g-1) and unchanged production rates of alanine (43 +/- 9, 40 +/- 7, and 51 +/- 5 nmol min-1 g-1) and ammonia (49 +/- 15, 45 +/- 13, and 54 +/- 13 nmol min-1 g-1). Similarly, when intestines were vascularly perfused 2 or 9 days after dexamethasone injection (0.45 mg kg-1 BW), net Gln uptake also remained unchanged (-88 +/- 16 and -84 +/- 11 nmol min-1 g-1). There was, however, a shift in nitrogenous products of Gln metabolism from ammonia (-31% and -38%) to alanine (+16% and +64%). Thus, the failure of dexamethasone to increase Gln uptake in the isolated rat intestine may indicate that rather than acting directly on the mucosa, dexamethasone could regulate intestinal Gln consumption in vivo by indirect mechanisms possibly involving extramucosal tissues. Dexamethasone pretreatment may modulate the pattern of nitrogenous products in portal venous blood presented to the liver and thus support enhanced nitrogen loss through ureagenesis by metabolic cooperation between gut and liver. PMID- 1759047 TI - Total denervation of the pancreas does not alter the pancreatic polypeptide induced inhibition of pancreatic exocrine secretion in dogs. AB - Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg-1 h-1 secretin and 50 ng/kg-1 h-1 caerulein over 3 h. One hour after starting the infusion, 400 pmol kg-1 h-1 porcine PP were administered over 1 h. Pancreatic bicarbonate and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms. PMID- 1759048 TI - Metabolism during normoxia, hypoxia and recovery in the newborn kitten. AB - We questioned whether the hypoxia-induced drop in aerobic metabolism in newborns necessitates an oxygen debt, and whether in such a case the debt is payed upon recovery. Aerobic metabolism (VO2 and VCO2) was computed each 30 sec in 15 newborn kittens (age 2-5 days) using an open flow system during normoxia, 30 min of hypoxia, and 30 min of recovery for two levels of hypoxia, 10% and 15% inspired O2. On a separate occasion, venous lactate levels were measured in normoxia and immediately following hypoxia. As expected, VO2 and VCO2 dropped in hypoxia. The decline started within 2 min, and the average decrease during hypoxia was -25% in 15% O2 and -36% in 10% O2. During recovery after 15% and 10% O2 aerobic metabolism was, respectively, below or equal to the normoxic value, whilst lactate was, respectively, the same or above the normoxic value. We conclude that in the kitten (1) the hypoxia-induced drop in aerobic metabolism is accompanied by no (15% O2) or small (10% O2) anaerobic metabolism, and (2) a post hypoxic metabolic depression can persist during recovery. PMID- 1759049 TI - Role of leukocyte depletion in noncholinergic bronchoconstriction of guinea pigs. AB - To test the role of leukocytes in the activation of afferent C-fibers in the lung, 33 guinea pigs, 18 control and 15 experimental or leukocyte depleted, were used. The leukocyte depletion was accomplished with an intraperitoneal injection of cyclophosphamide (100 mg/kg) 96 h prior to the study. On the day of the study, bronchial constriction was produced either by exsanguination (n = 17) or by capsaicin injection (16 micrograms/kg, i.v.) (n = 16) in anesthetized-paralyzed animals. Venous blood samples were collected for leukocyte counts. At 1-30 min following the above treatment, the maximal expiratory flow maneuver was performed and a decrease in the maximal expiratory flow at 50% baseline total lung capacity (Vmax50) was used as an index of bronchoconstriction. The leukocyte count decreased significantly following the pretreatment with cyclophosphamide [an average of 6217 +/- 612 (control) vs. 2242 +/- 334/mm3 (experimental)]. Exsanguination caused a gradual decrease in Vmax50 with time, indicating a temporal increase in bronchoconstriction. Capsaicin injection, on the other hand, caused an immediate (1 min) marked bronchoconstriction, which attenuated gradually with time. At a specific time point, leukocyte depletion did not produce any significant change in Vmax50 compared to the control group for both types of bronchoconstrictions. Based on these results, we conclude that leukocytes may play an insignificant role in the bronchoconstriction caused by the activation of afferent C-fibers in guinea pig lungs under our experimental conditions. PMID- 1759050 TI - Pressure-volume properties of the upper airway in man. AB - We report a method of measuring the static pressure-volume properties of the upper airway in unanesthetised humans. In 10 normal subjects the pressure in the upper airway was measured during aspiration of air in 10 ml decrements from 30-40 ml above resting volume to 30-40 ml below resting volume, with the glottis closed voluntarily and the oro-pharyngeal muscles relaxed. The pressure-volume properties of the upper airway were well described by the pressure-volume rate upper airway elastance (UAE, cmH2O/ml). The mean (+/- 95% CI) UAE measured at near total lung capacity and with the neck in neutral position for all runs in all subjects was 0.22 +/- 0.06 cmH2O/ml. When UAE was measured repeatedly on different days the greatest change observed was from a mean value of 0.17 cmH2O/ml on one day to 0.25 cmH2O/ml on another, and the standard deviation of the means from different days ranged from 0.01 to 0.04. Neither hypoxia (SaO2 80 85%) nor hyperoxic hypercapnia (PETCO2 65-75 mmHg) had any influence on UAE. Maximal extension of the neck did not affect UAE, but flexion of the neck was associated with a rise in UAE from a mean of 0.23 +/- 0.05 cmH2O/ml to a mean of 0.53 +/- 0.14 cmH2O/ml. UAE was not affected by the lung volume at which measurements were made. We conclude that upper airway pressure-volume properties can be measured non-invasively in man, and that in their linearity, reproducibility and lack of sensitivity to hypoxia and hypercapnia they resemble those of experimental animals. PMID- 1759051 TI - Regional compliance and bronchial pressure-diameter relationships in excised pig lungs. AB - We estimated the magnitude of parenchymal interdependence in excised pig lungs by measuring small airway diameter during homogeneous and nonhomogeneous lung inflation, by comparing the ratio of the specific compliance of the lung (Cl) to the specific compliance of a single lung region (Cs) and by using a continuum mechanics analysis to estimate the pressure at the interface between a single lung region and the surrounding lung. We found that the diameter of airways in a single lung region increased when the lung was held at a transpulmonary pressure (Ptp) of 5, 10 or 15 cmH2O and pressure in the region was increased by up to Ptp + 15 cmH2O, indicating that the surrounding lung offered little resistance to expansion of the lung region. The ratio of Cl to Cs averaged 1.22 (n = 5 lungs), indicating that the parenchyma surrounding the lung region caused a small reduction in its distensibility. When the lung was held at a Ptp of 5 cmH2O, pressure at the interface was estimated to be 1.1, 0.8 and -1.9 cmH2O when pressure in the single lung region was 15, 10 and O cmH2O, respectively. The relatively small change in boundary pressure from pleural pressure as the region was inflated or deflated indicated that the mechanical interaction between adjacent lung regions was small. Taken together, these results confirm the prediction of a small interdependence effect as determined by measurements of the distensibility and distortability of the pulmonary parenchyma. PMID- 1759052 TI - Mechanical properties of respiratory muscles in primates. AB - We examined the in-vitro mechanical characteristics of the diaphragm and parasternal intercostal muscles in adult baboons. At optimal length (Lo) the parasternal intercostal muscles were consistently faster than the diaphragm as judged by a shorter time-to-peak tension and a reduced twitch-to-tetanus ratio. However, maximal absolute force at Lo, corrected for cross-sectional area, revealed that the inherent strengths of both inspiratory muscles were identical (31.5 +/- 3.2 N/cm2 for diaphragm vs 29.5 +/- 1.1 N/cm2 for parasternal intercostals). Moreover, at submaximal stimulation rates, the parasternal intercostals produced significantly less tension at Lo than the diaphragm. At lengths less than Lo, however, the parasternal intercostal muscles generated significantly less tetanic tension than the diaphragm. These differences are similar to previously reported values in dogs (Farkas et al. (1985) J. Appl. Physiol. 59: 528-535). Thus, based on our findings, it appears that within a given species, the parasternal intercostals are quite different in mechanical terms from the diaphragm. Since both muscles are recruited at all levels of ventilation, including quiet breathing, these differences do not appear to be related to the activation levels. Moreover, since the present results were similar to those in dogs, the differences between both muscles do not appear to be affected or altered by body habitus. PMID- 1759053 TI - Thermal effects on ventilation in cats: participation of carotid body chemoreceptors. AB - In pentobarbitone anesthetized cats, raising body temperature from 37 to 40 degrees C by external heat increased respiratory frequency, tidal volume, frequency of spontaneous gasps and mean inspiratory flow. It reduced end-tidal CO2 pressure, together with inspiratory and expiratory durations. After bilateral section of the carotid nerves, raising body temperature still induced hyperventilation, but the increase in gasp frequency was less pronounced and no significant change in tidal volume was observed. In comparison to steady ventilatory values in the intact condition, significant reductions in tidal volume at 38 degrees C and in gasp frequency at 37, 39 and 40 degrees C were observed after bilateral carotid neurotomy. Brief hyperoxic tests induced transient decreases in tidal volume and increases in end-tidal CO2 pressure which were significantly larger at 40 degrees C than at 37 degrees C. These changes disappeared after bilateral carotid neurotomy. Anesthetic block of both carotid nerves produced transient reductions in tidal volume at any given temperature. We conclude that carotid body afferents contribute to the hyperventilation evoked by hyperthermia. After their interruption, such contribution is replaceable from other thermal afferents. PMID- 1759054 TI - A decrease in nasal CO2 stimulates breathing in the tegu lizard. AB - Tegu lizards decrease ventilatory frequency (f) when constant CO2, as low as 0.4%, is delivered to the nasal cavities. In contrast, CO2, as high as 6%, pulsed into the nasal cavities during the expiratory phase of the breathing cycle does not alter f. The purpose of the present study was to investigate further the effect of nasal CO2 pattern on f in tegu lizards. Specifically, we tested: (1) whether f was affected by CO2 delivered to the nasal cavities during the inspiratory phase of the breathing cycle, and (2) whether pulsed decreases in nasal CO2 from 4% to 2% and from 4% to 0% would remove the f inhibition caused by constant nasal CO2. Ventilation was measured using a pneumotachograph and pressure transducer in-line with an endotracheal T-tube inserted through the glottis. CO2 was delivered to the nasal cavities through small tubes inserted into the external nares. Ventilatory frequency was not significantly altered when 4% CO2 was pulsed into the nasal cavities during inspiration. Dropping the CO2 in the nasal cavities from 4% to 0% at either 15 cycles/min (0.25 Hz) or for one cycle stimulated breathing. There was no significant difference between the f response to a drop in CO2 from 4% to 0% and that to a drop in CO2 from 4% to 2%. The failure to link the phasic CO2 ventilatory response to a phase in the respiratory cycle indicates that the nasal CO2 receptors do not participate in the breath-by-breath regulation of breathing in these lizards. The observation that small decreases in nasal CO2 abolished the f inhibition caused by constant nasal CO2 provides further evidence for the ability of the nasal CO2 receptors to distinguish between pulsed and constant CO2. PMID- 1759055 TI - Flow-mediated vasodilatation of the main pulmonary artery. AB - This study compares the independent effects of flow (Qpa) and transmural pressure (Ppa) on the diameter (D) and length of a segment (L) of the main pulmonary artery (MPA) in anesthetized open-chested dogs. Qpa was increased by a shunt from the left lower lobe pulmonary artery to an external jugular vein. Ppa was increased with positive end-expiratory pressure (n = 5), or with a femoral arteriovenous shunt (n = 5). Mean Ppa, Qpa, D and L were calculated by averaging over a single cardiac cycle selected at end expiration of successive breaths. The independent effects of Ppa and Qpa on MPA dimensions were determined by multiple linear regression. The effects of Ppa delta D%/delta P% = 0.153 +/- 0.03 SE) and Qpa (delta D%/delta Q% = 0.021 +/- 0.004 SE) on D were similar in both groups of dogs. Changes of L (delta L%/delta Ppa% = 0.168 +/- 0.042 SE and delta Qpa% = 0.033 +/- 0.006 SE, n = 5) were similar to the corresponding changes of D. We conclude that the effects of flow are small relative to pressure and that flow not only causes vasodilatation but also vasoelongation of the MPA. PMID- 1759056 TI - Intracellular acid-base responses to environmental hyperoxia and normoxic recovery in rainbow trout. AB - Exposure of rainbow trout to environmental hyperoxia (PIO2 approximately 530 Torr) resulted in an extracellular respiratory acidosis which was fully compensated by 72 h; return to normoxia (PIO2 approximately 145 Torr) at this time induced a metabolic alkalosis which was corrected by 24 h. Intracellular pHi ([14C]DMO method), fluid volumes [3H]PEG-4000 method), and electrolytes were monitored. Environmental hypercapnia (PICO2 approximately 6.5 Torr) was employed to confirm that intracellular responses were specific to respiratory acidosis. Gill pHi did not change during respiratory acidosis despite a very low non-HCO3- buffer capacity, but gill ICFV decreased markedly. A large loss of gill intracellular [Cl-]i in excess of [Na+]i, combined with a substantial gain in [K+]i, contributed to gill pHi regulation by raising branchial [SID]i. In weakly buffered brain tissue, active adjustment of pHi started within 3 h, but two well buffered tissues, RBC and white muscle, exhibited compounding metabolic acidoses during the first 12-24 h. The muscle response was associated with small increases in ICFV and [Cl-]i, and a large decrease in [K+]i which reduced muscle [SID]i. We hypothesize that this initial export of K+ and basic equivalents served to regulate pH in more critical compartments (e.g. gills, brain) at the expense of muscle acidosis. By 48 h, pHi restoration in all tissues was complete, in advance of pHe regulation (72 h). Return to normoxia at 72 h elevated muscle, brain, and gill pHi, but there was no evidence of a comparable 'altruistic' role of muscle during this metabolic alkalosis. Regulation of pHi was complete by 24 h recovery, accompanied by partial or complete restoration of intracellular ions and fluid volumes. PMID- 1759057 TI - Clinical syndromes associated with tumors of the female genital tract. AB - Tumors of the female genital tract may be associated with a variety of unusual clinical manifestations. Uncommon endocrine and paraendocrine syndromes include production of human chorionic gonadotropin by tumors other than those of germ cell origin, hyperthyroidism associated with struma ovarii and gestational trophoblastic disease, the carcinoid syndrome, the Zollinger-Ellison syndrome, hypercalcemia, Cushing's syndrome, hypoglycemia, hypertension related to renin or aldosterone production, hyperprolactinemia, inappropriate secretion of antidiuretic hormone, and virilization associated with Nelson's syndrome and placental site trophoblastic tumor. Paraneoplastic syndromes associated with gynecological tumors include disorders of the nervous system, connective tissue, and skin, as well as hematologic abnormalities and the nephrotic syndrome. Heritable and other congenital syndromes associated with these tumors are the Peutz-Jeghers syndrome, the nevoid basal-cell carcinoma syndrome, Ollier's disease and Maffucci's syndrome, hereditary leiomyomatosis, ataxia telangiectasia, von Hippel-Lindau's disease, thyroid abnormalities associated with Sertoli-Leydig cell tumors, and Carney's complex. Other syndromes associated with tumors of the female genital tract include Meigs' syndrome, hyperamylasemia, uveal melanocytic lesions, and pyrexia. PMID- 1759058 TI - Pseudoneoplastic glandular lesions of the uterine cervix. AB - Diverse nonneoplastic glandular lesions of the uterine cervix may occasionally be misinterpreted as premalignant or malignant. These processes include papillary endocervicitis, tunnel clusters, deep glands and deep nabothian cysts, microglandular hyperplasia, mesonephric hyperplasia, diffuse laminar endocervical glandular hyperplasia, glandular hyperplasia not otherwise specified, tubal metaplasia, intestinal metaplasia, endometriosis, Arias-Stella reaction, changes secondary to extravasation of mucin, and various infectious and reactive atypias. Although these lesions may have abnormal architectural and/or cytologic features, their appearances differ from those of any of the various adenocarcinomas of the cervix or their precursors. Familiarity with the histologic features of these lesions is essential to avoid a misdiagnosis and potential mismanagement of a benign condition. PMID- 1759059 TI - Metastatic tumors in the ovary: a problem-oriented approach and review of the recent literature. AB - Metastatic tumors account for a significant proportion of the ovarian tumors that cause major problems in diagnosis for the surgical pathologist. This subject is reviewed with a consideration of the various patterns and cell types encountered in these tumors. The first two categories considered, tumors with endometrioid like and mucinous appearances, include a variety of neoplasms originating in the gastrointestinal tract and its appendages that simulate closely primary ovarian endometrioid and mucinous tumors. Other important categories reviewed include several varieties of metastatic tumors with follicle-like spaces, small cell malignant tumors, and tumors characterized by cells with abundant eosinophilic cytoplasm. The review also includes a discussion of the general considerations that are helpful in the distinction of primary and metastatic ovarian tumors. Important recent reports in the literature concerning metastatic tumors are additionally summarized. PMID- 1759060 TI - Pathology of the peritoneum: a review of selected topics. AB - Mesothelial lesions of the peritoneum may pose significant diagnostic problems. Accurate identification of these lesions is important because of their distinctive behavior and treatment requirements. This review discusses the clinical, pathological, and differential diagnosis of a variety of mesothelial lesions of the peritoneum, which includes mesothelial hyperplasia, multilocular peritoneal inclusion cysts (benign cystic mesothelioma), well-differentiated papillary mesotheliomas, and diffuse malignant mesothelioma, and the role of immunohistochemistry in the distinction from the more common primary peritoneal serous carcinomas. In addition, borderline serous tumors, psammocarcinomas, and solitary fibrous tumors of the peritoneum are briefly mentioned. PMID- 1759061 TI - [The Nottingham Health Profile as an example of a tool for measuring the quality of life in health]. PMID- 1759062 TI - [Encelopathies caused by prions]. PMID- 1759063 TI - [For the arterial pressure, the brain: a creed! "The scientific observation is always a polemic observation" (G. Bachelard)]. PMID- 1759064 TI - [False hyperphosphoremia in multiple myeloma. Interference of monoclonal immunoglobulin G with the determination of blood phosphorus level]. AB - A case of pseudohyperphosphataemia detected in a male patient with multiple IgG myeloma is reported. Phosphataemia, measured by a technique without previous deproteinization, reached 5.66 mM before any treatment and varied with treatment induced changes in monoclonal immunoglobulin levels. Conversely, normal phosphataemia levels were found in blood samples taken before and after treatment when serum was deproteinized. This pseudohyperphosphataemia resulted from an increase in optic density due to interference between monoclonal immunoglobulin and the molybdic reagent used to determine phosphataemia. A retrospective investigation yielded three similar cases: two in patients with myeloma and one in a patient with non-myelomatous monoclonal dysglobulinaemia. A brief prospective study showed that this phenomenon was relatively frequent, as it was found in 2 out of 9 patients with monoclonal immunoglobulin (IgG in all 9 cases). These data indicate that the finding of marked hyperphosphataemia in subjects with monoclonal dysglobulinaemia should always prompt a control assay performed on deproteinized blood. PMID- 1759065 TI - [Diagnostic delay in Horton's disease. Analysis of the diagnostic delay based on a retrospective study of 130 cases]. AB - Temporal arteritis (Horton's disease) is a multifocal granulomatous arteritis which affects elderly people. Its prognosis depends upon the risk of blindness. In a retrospective study of 130 patients we paid special attention to the delay in diagnosis and its relation to the occurrence of ophthalmic complications. In 73 patients (56.2%), this delay exceeded 3 months and reached more than one year in 22 of them. It was not influenced by age or sex. In requests for admission, the diagnosis of temporal arteritis was suggested in only 28 of the 130 cases; 17.7% of the patients were blind. There was a significant increase in the occurrence of ophthalmic lesions when the diagnosis was delayed by 2 to 6 months. In 6 cases, blindness had been preceded by transient amaurosis. These findings confirm that temporal arteritis is belatedly diagnosed by practitioners and that blindness could be avoided by an earlier diagnosis. PMID- 1759066 TI - [Alveolar hemorrhage, glomerulonephritis and anti-cytoplasmic polynuclear antibodies]. AB - The value of antineutrophilic cytoplasmic antibodies (ANCA) was assessed in the diagnosis and chronic treatment of 7 patients with microscopic polyarteritis or Wegener's granulomatosis. All patients had oligoimmune glomerulonephritis with segmental and focal necrosis and presented with anaemia. Five of them had alveolar haemorrhage with haemoptysis and infiltrates at radiography. ANCA were assayed by indirect immuno-fluorescence on ethanol-fixed neutrophils and were strongly positive, with a cycloplasmic aspect in 5 cases and a perinuclear aspect in 2 cases. Initial remission with fall in ANCA titres was obtained with corticosteroids, cyclophosphamide and sometimes plasmapheresis (5 patients), but frequent relapses with re-elevation of ANCA titre occurred when treatment was reduced. It is concluded that ANCA are very helpful in the diagnosis of systemic vasculitis, notably in cases with first-time alveolar haemorrhage. They also facilitate monitoring and therapeutic decisions, since relapses are frequent. PMID- 1759067 TI - [Anomalies of lipid metabolism in diabetes mellitus]. AB - Atheroma is by far the most common cause of mortality in diabetic patients (66 to 75% of deaths). Several physiopathological mechanisms are suspected to account for the greater frequency and severity of atheroma in diabetes. Among these, lipid abnormalities hold first rank and include not only quantitative but also qualitative abnormalities of lipoproteins altering their kinetics and bindings to membrane receptors. The main quantitative abnormalities are an increase of triglycerides and very low density lipoproteins (VLDL) and a fall in high density lipoproteins (HDL) and their HDL2 subfraction. Qualitative abnormalities include non-enzymatic glucosylation of apoproteins, changes in lipoprotein size and increase in their triglyceride content, and excessive oxidation of low density lipoproteins (LDL). Both quantitative and qualitative abnormalities of lipoproteins are present in non-insulin-dependent diabetes, whereas only qualitative abnormalities are observed, as a rule, in treated insulin-dependent diabetes. The physiopathology of lipid metabolism disorders is complex, possibly multifactorial and still imperfectly known. However, such factors as modification of insulin status, hyperglycaemia and obesity frequently associated with diabetes, are thought to be involved. PMID- 1759068 TI - [Classification of malignant non-Hodgkin's lymphoma]. AB - The authors list the reasons which make it important and useful to classify non Hodgkin's malignant lymphomas (ML) and discuss the criteria of a convenient classification. They also describe the principles of updated Kiel's classification and the various entities recognized. These entities are divided into type B and type T ML, each type in turn being divided into low malignancy, high malignancy and rare forms. PMID- 1759069 TI - [Digestive manifestations of food hypersensitivity in adults]. AB - Food allergy, synonymous with food hypersensitivity (FHS), is defined as an immunologically-mediated adverse reaction to food. Initiation of FHS could result from a break in the immune mucosal barrier with abrogation of oral tolerance. Food hypersensitivity is mostly due to immediate-type reaction involving IgE dependent mastocytes activation. Changes in intestinal function and structure have been mainly studies in an animal model of rat sensitized to egg albumin. Intraluminal antigen challenge resulted in abnormalities of gut absorption, secretion and motility in sensitized rats. In man, experimental data are scarce. Gastrointestinal manifestations of immediate FHS are varying and unspecific. A role for FHS in irritable bowel syndrome is debated. Participation of delayed type FHS to digestive diseases is still questionable, but eosinophilic gastroenteritis might be an example. In clinical practice, diagnosis of FHS demands rigorous criteria. Double blind placebo-controlled food challenge has eventually proved to be the "gold standard" test for FHS diagnosis. PMID- 1759070 TI - [Portal hypertension and hypervitaminosis A. Apropos of 2 cases and review of the literature]. AB - Portal hypertension consecutive to hypervitaminosis A has seldom been well documented. Two cases are reported here. The first case concerns a 39-year old woman who had taken meladinine (8-methoxypsoralen) for the purpose of tanning. In the second case, a 43-year old woman had absorbed Plethoryl (a combination of tiratricol, cyclovalone and retinol) in order to lose weight. Both patients had histological hepatic lesions, such as hypertrophic Ito cells, perisinusoidal cirrhosis and spontaneous autofluorescence, suggestive of vitamin A overload, associated with a hepatic vein pressure gradient of 10 mmHg or more and high liver concentrations of vitamin A. The responsibility of Plethoryl in case 2 is beyond any doubt, but the mechanism of hypervitaminosis in case 1 is controverted. A review of the literature has provided detailed information on the signs of vitamin A overload, the frequency of which is probably underestimated. Patients with portal hypertension of unknown origin should be investigated for hypervitaminosis A. PMID- 1759071 TI - [Type B Niemann-Pick disease and sea-blue histiocytes syndrome]. AB - We report two new cases, in the same family, of type B Niemann-Pick disease associated with sea-blue histiocytes syndrome. In one patient the disease was revealed by spontaneous rupture of the spleen. The sea-blue histiocytes syndrome is due to the histiocytes being overloaded by ceroids, and it usually occurs in a context of blood disease or thesaurismosis. Twenty-five cases of sea-blue histiocytes syndrome associated with type B Niemann-Pick disease have been reported, with rupture of the spleen in two of them. The link between the two conditions is the transformation into ceroids of the sphyngomyelin accumulated in histiocytes. PMID- 1759072 TI - [Musical hallucinations]. AB - Musical hallucinations are rarely reported. Acquired deafness play an important role in their development. The anatomical and neurophysiological substrates for the musical hallucinations are unknown. Most authors related the perceptual disturbance to organic origin (central or peripheral). PMID- 1759073 TI - [Temporal artery syndrome in amyloidosis AL associated with myeloma]. AB - The authors report a case of amyloidosis AL associated with light lambda chain myeloma, mimicking giant cell temporal arteritis. The normality of inflammatory proteins, the primary resistance to corcicosteroids and the results of temporal artery biopsy (amyloid deposits without giant cell granuloma) excluded a diagnosis of giant cell arteritis associated with amyloidosis. The most probable mechanism was infiltration of branches of the external carotid artery. In patients with temporal arteritis, amyloidosis must be suspected and sought, particularly in case of monoclonal dysglobulinaemia or manifestations that are not typical of giant cell temporal arteritis. The prognosis of vascular amyloidosis seems to be more favourable than that of the classical visceral types. The primary amyloidosis of these patients must be treated with melphalan combined with prednisone and colchicine. PMID- 1759074 TI - [Hyperthyroidism and immune hemolytic anemia following amiodarone therapy]. AB - We report the cases of two patients who, after prolonged amiodarone therapy developed hyperthyroidism and immune haemolytic anaemia. Antibodies were of the IgG type and non-specific at elution. A search for other causes of haemolytic anaemia with positive Coombs' test gave negative results. Antiamiodarone antibodies have recently been discovered; they reflect an immunological disturbance due to this drug and might be responsible for some of the undersirable effects of amiodarone. In our patients, hyperthyroidism and haemolytic anaemia were induced by a dual mechanism: accumulation of amiodarone and induction of an effect of this drug on the immune system. PMID- 1759075 TI - [Giant cell arteritis of gynecologic localization. Discussion of a new case]. PMID- 1759076 TI - [Danger to aquariophils. Apropos of a case of poisoning by Pterois volitans]. PMID- 1759077 TI - [Importance of rehydration in the treatment of symptomatic hypercalcemia]. PMID- 1759078 TI - [Lipo-atrophy of the buttocks after intramuscular injection of adrenal cortex hormones]. PMID- 1759079 TI - Developments in the treatment of gastric cancer. PMID- 1759080 TI - Prolonged survival of stomach cancer patients after extensive surgery and adjuvant treatment: an overview of the Japanese experience. AB - The 5-year survival rate of resected stomach cancer patients, which had been nearly 20% or less in the 1950s, has now been increased to more than 60%. Such a remarkable improvement was analyzed from the data of the National Registry or of the nationwide cohort studies. Standardization of the operative method involving extensive lymph node dissection, which has prevailed since the mid-1960s, was the leading factor in this improvement. Development of improved techniques for early diagnosis increased the rate of detection of early cancer and the rate of early cancer per resected cases amounts to more than 30% in major institutions as of 1981. Adjuvant chemo-immunotherapy administered over a long postoperative period was confirmed to elevate the cure rate substantially. As new anticancer drugs recently developed in Japan, UFT (Uracil/Tegafur mixture) and HCFU (Carmoful) were introduced. Optional use of regional therapy such as arterial infusion chemotherapy or intracavital biological response modifiers (BRM) injection are among the latest treatment possibilities. PMID- 1759081 TI - Gastric cancer mass survey in Chile. AB - A Chilean publication in 1969 reported the 5-year survival rate of gastric cancer to be 12% of operated patients and only 3% of all patients diagnosed with gastric cancer. Encouraged by the excellent results obtained in Japan through a massive study of the population, Chile initiated in 1978 a program for massive detection of gastric cancer. From May 1978 to December 1986, 42,492 persons were screened under this system. Gastric cancer was detected in 0.43% in the massive group, and in 1.27% in the symptomatic group. The rate of early cancer detected per all gastric cancer was 14.69% in the former and 11.02% in the latter group. Gastric ulcer was found to be located more in the upper third of the stomach and less in the lower third, which may call attention in comparison with the foreign literature. PMID- 1759082 TI - Recurrence of early gastric cancer. AB - We investigated the postoperative deaths and recurrence among 673 patients with early gastric cancer who had undergone gastric resection at the National Kyushu Cancer Center Hospital from March 1972 to December 1988. The mode and time of recurrence were assessed with reference to the clinicopathological findings at initial surgery. Fifteen patients (2.2%) died of cancer recurrence, and 18 patients (2.7%) developed recurrence (3 patients are currently alive after reoperation). A comparison of modes of recurrence revealed that the incidence of hematogenous recurrence was the highest with nine cases, followed by recurrence in the remnant stomach in three cases and by local, lymph node, and peritoneal recurrences in two cases each. Twelve patients developed recurrence within 5 years after operation (early recurrence) and six patients after 5 years (late recurrence). Cases positive for cancer cell invasion into intralesional veins at initial surgery had a significantly higher recurrence rate than negative cases (P less than 0.001). Thus, venous invasion was the most important factor for the development of recurrence in the patients with early gastric cancer. PMID- 1759083 TI - Endoscopic treatment of early gastric cancer. AB - Laser therapy and endoscopic strip biopsy for early gastric cancer are useful measures from our experience. It is considered that the larger lesion of early cancer should be treated by laser therapy and the smaller lesion by strip biopsy. However, endoscopic therapy as a curative treatment still presents problems. Clinical trials with laser therapy has to accumulate to ascertain the effectiveness of laser on the gastric wall. Also, endoscopic treatment methods are limited to patients who cannot be admitted to surgery. Furthermore, it is difficult to judge the metastasis to lymph nodes surrounding the stomach with present diagnostic capabilities. Wider application of these endoscopic treatment methods will follow when these difficulties are overcome. PMID- 1759084 TI - Surgical treatment of gastric cancer: retrospective survey of 1,704 operated cases with special reference to total gastrectomy as the operation of choice. AB - Total gastrectomy is discussed as the operation of choice among different surgical approaches for gastric carcinoma. We prefer the performance of an elective total gastrectomy with systematic lymphadenectomy (compartments I and II) and obligatory splenectomy. A retrospective study of 1,704 consecutive cases of gastric carcinomas showed a better outcome following total gastrectomy in relationship to distal subtotal gastrectomy, but these results cannot be used as evidence because of the lack of a prospective study. Nevertheless, a precise analysis of our cases in regard to tumor site and tumor type could show a frequency of only 6% to maximally 30%, in which elective total gastrectomy may represent a procedure too extensive to justify for an oncological course. PMID- 1759085 TI - Improvement in treatment results of gastric cancer with surgery and chemotherapy: experience of 9,700 cases in the Cancer Institute Hospital, Tokyo. AB - Treatment results of 9,741 cases of gastric cancer treated at the Cancer Institute Hospital, Tokyo during the past 42 years were retrospectively analyzed. Resectability was 89.6% (94.1% for 1960-1988) and operative mortality was 1.9% (1.5% for 1960-1988). Five-year survival rate was 48.5% (54.9% for 1960-1988) for all cases, 68.8% (73.1% for 1960-1988) for patients with curative surgery, and 4.7% (4.9% for 1960-1988) for those with noncurative surgery. Curative rate was improved twofold among patients with curative gastrectomy. Postoperative adjuvant chemotherapy had a marginal benefit for stage II and III disease. Improvement could be attributed mainly to the relative increase in early gastric cancer, and partly to the extended surgeries for stage III and IV cases, such as systemic lymphadenectomy and combined resection of involved adjacent organs. Multimodality therapy is expected to control the relapse of peritoneal dissemination (14.2%) and hematogenous metastasis (8.9%). PMID- 1759086 TI - Coeliac axis-oriented approach in surgery for advanced gastric cancer. AB - To achieve the systemic curative lymph node dissection in gastrectomy for advanced gastric cancer, coeliac axis-oriented approach was proposed. Mobilization of the spleen as well as the tail and body of the pancreas from the left retroperitoneum and Kocher's maneuver lifting up the hepatoduodenal ligament and head of pancreas from the right retroperitoneum permits the observation of the coeliac axis under direct vision and enables the para-aortic node dissection with ease. This approach was applied to 131 cases with advanced gastric cancer with neither mortality nor notable complication. PMID- 1759087 TI - Type-oriented therapy for gastric cancer effective for lymph node metastasis: management of lymph node metastasis using activated carbon particles adsorbing an anticancer agent. AB - Activated carbon particles are taken selectively up by lymphatics when injected into the tissues and visualize regional lymph nodes colored black. Furthermore, carbon particles adsorb a large amount of the anticancer agent mitomycin C (MMC) on their surface and release the drug reversibly. Using these properties of activated carbon particles, we have applied it for lymph node dissection and chemotherapy of lymph node metastasis. After injection of carbon particles, regional lymph nodes of the stomach were found to be black; blackened lymph nodes extending widely from perigastric to para-aortic nodes were identified from other structures. Four hundred and twenty-four patients with gastric cancer were treated with this method for lymph node metastasis during 1984-1988. Involved nodes were generally colored in high incidence, about 70% of involved ones except for highly positive nodes, which was the same as noninvolved nodes. In highly positive nodes, the colored incidence was decreased to about 48%. The cumulative 5-year survival rate of the patients treated with this series was 74.6%, which was significantly higher than the figures without this method. PMID- 1759088 TI - Split-night studies: a new standard? Forcing the examination of outcome. PMID- 1759089 TI - Single night studies in obstructive sleep apnea. AB - The role of single night studies and the determinants of effective nasal continuous positive airway (CPAP) pressures were determined in 412 consecutive patients between 1984 and 1989. Patients chosen for analysis had an apnea index (AI) of greater than or equal to 20 hr-1 prior to CPAP. The AI was 67 +/- 30 hr 1, the body mass index (BMI) was 36 +/- 9 kg/m2, the age was 51 +/- 13 yr and the lowest oxygen saturation was 72 +/- 14%. Effective CPAP (9 +/- 3 cm H2O) was documented in 320 patients on single night studies and resulted in a 99% reduction in the frequency of obstructive events and improvement in the lowest O2 saturation to 94 +/- 5%. Only 18% of the variability in effective CPAP could be explained by AI and BMI. Single night studies are sufficient to establish effective CPAP in 78% of patients and offer considerable conservation of resources compared to routine multiple night studies. Effective CPAP pressures are variable and must be determined by incremental CPAP trials. PMID- 1759090 TI - Insomnia and use of hypnotics: study of a French population. AB - A cross-sectional study of insomnia and hypnotic use was performed in a sample of the French population. The quota method was used to select the sample of 1,003 subjects, with less than 3% substitution. Subjects were 15 years old and older and were representative of the French population based on gender, age, marital status and living environment. Subjects were asked questions relevant to the complaint of insomnia and hypnotic use and filled out questionnaires measuring anxiety and depression. The complaint of insomnia is common, even in the 15-24 year-old group. Overall, more women than men were afflicted. The largest group of insomniac subjects, and the group who most often used hypnotics "frequently and chronically", were women 45 years and older. Men presented a sharp increase in hypnotic use after 65 years of age. Ten percent of the entire sample used hypnotics, 8% for more than 6 months and 6.17% on a chronic and frequent basis. Retired and unemployed elderly were also chronic and frequent hypnotic users: aging and social isolation correlate with chronic and frequent hypnotic usage. Higher scores on anxiety and depression scales correlate with more frequent complaints of nocturnal sleep disturbances. Young individuals are a significant complainer group but use hypnotics rarely. A rural environment was associated, overall, with fewer insomnia complaints, but environment had much less impact on complaints and hypnotic use in the elderly than in other age groups. One may question whether, in the French population, hypnotic prescription and intake are not responses to a social rather than a medical problem. PMID- 1759091 TI - Prevalence and treatment of insomnia in the community: results from the Upper Bavarian Field Study. AB - In the Upper Bavarian Field Study a total of 1,536 persons (15 yr of age and older) were interviewed by research psychiatrists. The prevalence of insomnia (last 7 days) identified with the aid of the Clinical Interview Schedule (CIS) was 28.5% (mild: 15.0%; moderate/severe: 13.5%). For both sexes sleep disorders increased with age. The female preponderance of insomnia was mainly associated with the middle and older age groups. In contrast to other psychiatric disorders, sleep disturbances were not associated with social class. Moderate/severe insomnia was strongly related to psychiatric diagnoses, the use of psychiatric in and outpatient services and general hospitals. It also constituted a significant burden for the primary-care physicians, whereby the average annual consultation rate among mild (10.61) and moderate/severe insomniacs (12.87) was significantly higher compared to that for those without sleep disorders (5.25). A total of 33.7% of the insomniacs were treated with hypnotic and/or other psychotropic drugs during the week prior to the interview, whereby the drug consumption among moderate/severe insomniacs (48.5%) was significantly higher than that of mild insomniacs (20.4%). PMID- 1759092 TI - Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem. AB - There is little published literature on the correlation between subjective and objective efficacy of hypnotics. We wanted to determine whether there was a correlation between the patient's subjective evaluation of the efficacy of the hypnotic with the polysomnographic (PSG) findings. We studied 16 patients with chronic insomnia (sleep latency, greater than or equal to 30 minutes; total sleep time, greater than 240 but less than 420 minutes) for 11 nights who took placebos on nights 1 and 2, zolpidem (imidazopyridine) on nights 3-9 and placebo on nights 10 and 11. Patients completed a questionnaire each morning following PSG, which evaluated subjective sleep quality, sleep latency and total sleep time. These data were compared to PSG findings to answer specific questions about sleep latency reduction, efficacy of the hypnotic after a week's use, sleep quality after discontinuing the drug, and any correlation between subjective and objective measures. PSG findings indicated a shortened sleep latency, increased total sleep time, decreased total wake time and increased sleep efficiency when patients ingested zolpidem 30 minutes before bedtime. We found that after 7 nights (nights 3-9) the drug was still effective in reducing sleep latency and increasing total sleep time. Upon withdrawal (nights 10 and 11) sleep returned to baseline (nights 1 and 2). Subjectively, the patients confirmed those findings on the questionnaire, as well as a subjective reduction in the number of awakenings and, interestingly, a subjective increase in the time spent awake after sleep. Many of the objective variables we examined correlated highly with the subjective variables. While on zolpidem, subjects believed and were objectively shown to have a decreased sleep latency, increased total sleep time and decreased time awake before persistent sleep, although they tended to overestimate sleep latency and time spent awake before persistent sleep and underestimated total sleep time. Although the correlation between objective and subjective measures was high for the group, in individual patients there was an impressive difference between the two, and the highest coefficient of variation between a subjective and objective measures was 0.453. No correlations were found with subjective measures of refreshing quality of sleep, decrease in number of awakenings, how sleepy patients felt in the morning or their ability to concentrate in the morning. Thus, we believe the PSG remains the keystone in the evaluation of hypnotic efficacy. PMID- 1759093 TI - Postmarketing surveillance of zopiclone in insomnia: analysis of 20,513 cases. AB - The subjective response to the prescription drug zopiclone, an hypnotic agent belonging to the cyclopyrrolone family, was assessed under the usual conditions of prescription of an hypnotic in general practice. The study included 20,513 insomniac outpatients with at least two of the following symptoms: sleep onset latency longer than 1 hour, more than two nocturnal awakenings, early morning awakening 1 hour or more before scheduled time, total sleep time of less than 6 hours, complaint of tiredness on awakening. Insomniac patients were treated with zopiclone and followed for 21 consecutive days within the context of a follow-up surveillance study. The population was predominantly female (62.6%), and the mean age was 52.3 years. The dosage of zopiclone prescribed at the inclusion visit was 7.5 mg per day in 87.5% of the cases and 3.75 mg per day in 10.5%. A total of 93.8% of the patients completed the survey. Spiegel questionnaire improved during the 21-day survey, and 9.2% of the patients reported at least one adverse event that led to treatment discontinuation in only 2.8% of the population. No serious or unexpected adverse events were reported. PMID- 1759094 TI - Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12). AB - Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15 year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed. PMID- 1759095 TI - Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders. AB - Over a 5-yr period, 19 adults presented to our sleep disorders center with histories of involuntary, nocturnal, sleep-related eating that usually occurred with other problematic nocturnal behaviors. Mean age (+/- SD) at presentation was 37.4 (+/- 9.1) yr (range 18-54); 73.7% of the patients (n = 14) were female. Mean age of sleep-related eating onset was 24.7 (+/- 12.9) yr (range 5-44). Eating occurred from sleep nightly in 57.9% (n = 11) of patients. Chief complaints included excessive weight gain, concerns about choking while eating or about starting fires from cooking and sleep disruption. Extensive polysomnographic studies, clinical evaluations and treatment outcome data identified three etiologic categories for the sleep-related eating: (a) sleepwalking (SW), 84.2% (n = 16); (b) periodic movements of sleep (PMS), 10.5% (n = 2) and (c) triazolam abuse (0.75 mg hs), 5.3% (n = 1). DSM-III Axis 1 psychiatric disorders (affective, anxiety) were present in 47.4% (n = 9) of the patients, and only two patients had a daytime eating disorder (anorexia nervosa), each in remission for 3-7 yr. Nearly half of all patients fulfilled established criteria for being overweight, based on the body mass index. Onset of sleep-related eating was linked directly to the onset of SW, PMS, triazolam abuse, nicotine abstinence, chronic autoimmune hepatitis, narcolepsy, encephalitis or acute stress. In the SW group, 72.7% (8/11) of patients had nocturnal eating and other SW behavior suppressed by clonazepam (n = 7) and/or bromocriptine (n = 2) treatment. Both patients with PMS likewise responded to treatment with combinations of carbidopa/L-dopa, codeine and clonazepam. Thus, sleep-related eating disorders can generally be controlled with treatment of the underlying sleep disorder. PMID- 1759096 TI - Prevention of airway obstructions during sleep in infants with breath-holding spells by means of oral belladonna: a prospective double-blind crossover evaluation. AB - We investigated whether the brief airway obstructions seen during sleep in infants with breath-holding spells were controlled by the autonomic nervous system. We studied 20 infants, with a history of breath-holding spells and a median age of 12 wk (range 4-46 wk). During sleep they had a median of 6 airway obstructions per 10-hr recording (range 3-16 events), with a median duration of 8 sec (range 4-12 sec). No explanation was found for the airway obstructions. In every infant, a double-blind crossover challenge was conducted. It included oral administration of tincture of belladonna, equivalent to 0.01 mg/kg weight of atropine, and placebo syrup containing no belladonna. The belladonna, or the placebo, was administered at bedtime for 7 days, followed by a 7-day washout period. Another 7-day series of syrup administration was then undertaken. A nighttime polygraphic recording was made after each 7-day series. It was the belladonna, and not the placebo, that induced the disappearance of the obstructions in 10 infants; these were called "drug responsive". In 5 children no effect was observed after either the placebo or belladonna; these infants were defined as "drug unresponsive". In 4 subjects the obstructions disappeared after both belladonna and the placebo; the children were considered to have an "inconclusive response". One infant was excluded from the study because he developed an airway infection. It is concluded that in some breath-holding infants, obstructed breathing episodes during sleep disappear after the administration of an atropinic drug. The observation could indicate a role of the autonomic nervous system in the control of the upper airways during sleep in infants. PMID- 1759097 TI - Enforced 24-hour recovery following sleep deprivation. AB - The pattern of recovery sleep after sleep deprivation was investigated in healthy young adults. Six subjects experienced three experimental conditions (0, 24, and 48 hr sleep deprivation) in a Latin Square design. The recovery period consisted of a 24-hr enforced time in bed during which subjects were polysomnographically recorded beginning at 0800. To assess the differential effects of the deprivation conditions, the total sleep time on the 24-hr recordings was submitted to a six (4-hr block) by three (deprivation condition) multivariate analysis of variance. Subjects slept more following the 24- and 48-hr conditions when compared to the 0 hr condition. Across conditions, subjects slept more during the first 4 hr when compared to the remaining five blocks. Importantly, there was a significant interaction of sleep deprivation by 4-hr block. In block 1 sleep was differentially recovered between each condition with more sleep being recorded following longer hours of deprivation. In block 2 subjects in the 24- and 48-hr conditions slept comparable amounts and significantly more than those in the 0-hr condition. In blocks 3 and 4 only the 48-hr condition exhibited significantly more sleep than the 0-hr condition. However, significantly less sleep was found in block 6 following the 48-hr condition. Overall, subjects recovered 72% and 42% of the total amount of sleep lost during the 24- and 48-hr conditions, respectively. PMID- 1759098 TI - Middle-ear muscle activity (MEMA) and its association with motor activity in the extremities and head in sleep. AB - Middle-ear muscle activity (MEMA) in sleep was simultaneously recorded from both ears using extratympanic manometry. Head movement, speech movements, ankle flexion and wrist movement were monitored by electromyographic recording using surface electrodes at the back of the neck, second laryngeal notch, anterior tibialis and forearm muscle. Motor events recorded from these electrode placements were examined for correlation with MEMA to test the hypothesis that the middle-ear muscles are activated in conjunction with other motor activities, aside from eye movements, by a central motor command system. Phi coefficients were calculated for each subject; all were positive, thus indicating an association between MEMA and other noneye movement motor events. These results suggest that there is a central phasic motor system responsible for MEMA and associated phasic motor activity in sleep. PMID- 1759099 TI - Periodic hypersomnia: case report with biochemical and EEG findings. AB - We report on a 23-year-old patient with periodic hypersomnia. Electroencephalographic (EEG) background activity for this individual was slightly slowed in the EEG during an episode of hypersomnia, and intermittent slow activity was found in addition. Usual laboratory parameters were normal; however, leucine-enkephalin was markedly elevated in the plasma at that time, whereas free cysteine could not be demonstrated. Clinical findings were normal in the following years, and the EEG background activity returned to normal; leucine enkephalin and cysteine also returned to normal values. PMID- 1759100 TI - Pharmacological dissociation of EEG and behavior: a basic problem in sleep-wake classification. PMID- 1759101 TI - [Results of medicosurgical treatments of gastroesophageal reflux in asthma]. PMID- 1759102 TI - [Lasers and endoprosthesis in bronchopneumology]. AB - During the past decade lasers, especially the Neodymium: Yttrium-Aluminum-Garnet (Nd: YAG), have transformed interventional bronchoscopy. Recent improvements of tracheobronchial prostheses have further increased the therapeutic possibilities of endoscopy. Tracheobronchial obstruction by intraluminal tumeur, stenosis, or extrinsic compression can now be palliated successfully. The future of therapeutic bronchoscopy is bright. New techniques of optic spectroscopy will allow improved detection of laser induced tissue fluorescence. Refinements of laser technology and development of visualisation systems such as endoscopic echography and electronic videoendoscopy will lead to improved diagnostic and therapeutic capabilities. PMID- 1759103 TI - [Isolated cough and bronchial asthma]. AB - Over an 18-month period 31 patients (27 female and 4 male) were referred to the ENT department of our clinic for a 1-month to 14-year history of isolated non productive cough. As ENT examination, including posterior rhinoscopy, was normal, these patients were sent to the pneumology department. Physical examination and X ray films of the chest were negative, and the patients did not take an angiotensin converting enzyme inhibitor that could have induced this cough. Inhalation of acetylcholine lowered vital capacity by 32 +/- 14% and forced expiratory volume by 34 +/- 16%, a test which is the hallmark of bronchial hyperreactivity. Three patients were atopic. We believe that this cough can be the only manifestation of bronchial asthma. In these patients, cough was suppressed or strongly attenuated by the inhalation, 5 times a day, of salbutamol 200 mg puffs and beclomethasone dipropionate 250 mcg. In addition, the atopic patients were prescribed 10 puffs of sodium cromoglycate per day. Complaints of isolated non-productive cough must always suggest that possibility of bronchial asthma, and a bronchial provocation test must be performed to confirm this diagnosis. PMID- 1759104 TI - [Peculiar development of a case of pneumothorax]. PMID- 1759105 TI - [Peculiar bilateral opacities]. PMID- 1759106 TI - [Access of torsades de pointes in Legionnaires' disease: an uncommon adverse effect of erythromycin]. AB - We report the case of a 77-year-old man with legionnaires's disease who, immediately after an intravenous infusion of one gram of erythromycin presented with wave burst arrhythmia with widening of the QT space. The blood level of erythromycin at the time of this adverse reaction was the same as the peak observed in young subjects after intravenous administration of this drug. Fourteen similar cases were found in the literature. In vitro and in vivo studies have shown that erythromycin may exert on the cardiac muscle fibres an electrophysiological effect similar to that of class I antiarrhythmic agents. PMID- 1759107 TI - [Eosinophilic lung disease caused by filariasis. Apropos of a case]. AB - A 23-year-old male Pondichery native consulted for vesperal dispnoea. The main abnormalities detected were blood and alveolar eosinophilia and bilateral micronodular lesions at radiography. The parasitic origin of these symptoms was suspected, then confirmed by serological tests for filaria. The outcome was favourable after antiparasitic therapy. The histopathological, clinical and evolutionary features of pulmonary eosinophilic filiariasis are described, with emphasis on the treatment and on follow-up laboratory tests. PMID- 1759108 TI - The mathematical description of structures. AB - Any mathematical description of structures should start from a precisely stated definition of the concept of "structure". Unfortunately no universally accepted definition of this type exists. All that can be said is that the concept of "structure" is changing together with the modern physico-mathematical thought, so that different 'points of view' on the problem of the mathematical description of structures can be distinguished. The aim of this paper is to compare the explicative and predictive power of these different 'viewpoints' without entering into historical detail, in order to critically examine the limits and powers of the mathematical tools available today. PMID- 1759109 TI - Evolution in absence of mutation. AB - Each part of a living organism contains a concealed totality which can eventually express itself partially or totally. The extent of the expression is spatially and temporally defined by the morphogenetic field and the environment. Neither the field nor the genome are evolving units. Evolution is produced by the boundary conditions and results in progressive losses, to which the organisms responds. Genetic losses can stabilize the new balance. A living system can be fruitfully compared to a semiotic system. PMID- 1759110 TI - Behavioral pathway to evolutionary change. AB - The extreme malleability or plasticity of cells early in their development is mirrored to a certain, if lesser, degree in the psychological, behavioral, and neural functioning of developing organisms. The early developmental adaptability of organisms has significance for our understanding of evolution. It is the purpose of the present article to make a case for the extra-genetic or, better, the supra-genetic developmental basis of evolutionary change through the genesis of novel behavioral phenotypes. To make things as clear as possible, I contrast this developmental approach to evolution with the population-genetic model of the modern synthesis. I should say at the outset that the present theory can be integrated with the population-genetic model, with the exception of the radically different role ascribed to genes in the two viewpoints. PMID- 1759111 TI - The influence of inhibitors and other factors on cholinesterases. AB - Literature survey dealing with cholinesterases and effects of highly toxic organophosphorus compounds suitable for use as chemical weapons is given in introductory part of this work. There are nerve paralytical agents (NPA)--sarin, soman, VX and a model compound O-ethyl-S-(2-dimethylaminoethyl)-methyl phosphonothioate (EDMM). On the base of described scheme of intoxication with NPA, inhibition effect on cholinesterases, preferably on AChE as the most important factor involved in the mechanism of acute intoxication with NPA was studied. Intoxication of mice or rats with sarin and soman (2 x LD50) showed that time course of poisoning is faster than that for VX or EDMM. Inhibition of AChE in the blood was in good correlation with symptoms of intoxication and also with inhibition of AChE in the brain. The differences between inhibition effect of soman preferably uniform character of inhibition in the brain parts) and sarin (selective inhibition in the brain parts, with maximum in the frontal cortex and pontomedullar area) were observed. This selectivity was most marked for VX and EDMM intoxication (maximal inhibition in the part of the pontomedullar area containing reticular formation). The dose causing inhibition effect in the brain was assessed to be about 1% of the dose administered. The study of the effect of antidotal therapy (combination of atropine and reactivator) in vivo showed in mice and rats intoxicated with sarin non-uniform increase of AChE activity in the pontomedullar part depending on the dose and type of reactivator. The most marked effect was observed for methoxime. It was demonstrated that there exists good correlation between survival of experimental animals and the rest AChE activity in the pontomedullar part of the brain. AChE activity level critical for survival or death of the organism poisoned with NPA was assessed from these experiments; it was about 1-5% of normal values. By means of original method allowing continual monitoring of AChE activity in the blood, similar AChE reactivation was demonstrated, with highest effect for trimedoxime and methoxime. Using continual determination of the blood AChE activity following sarin, soman, VX and EDMM intoxication demonstrated that only a part of the dose administered caused inhibition effect in the blood; this part was determined to be practically 100% (i. v. administration); for other routes of administration this ratio was as follows: 50-80% (i. m.), 20-40% (i. p.), 6-16% (p. o.) and 1-5% (p. c.), respectively. Using this continual monitoring, the detoxication of sarin and soman was demonstrated. Detoxication of VX and EDMM was not observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1759112 TI - Severe limb ischemia syndrome. AB - In the course of the study of the syndrome of severe limb ischemia (SLI) in a representative clinical material of 300 patients and a number of experimental studies, we arrived to the proposal of this optimal methodical procedure for acute vascular closures of traumatic and non-traumatic origin in the limbs: a) In every injury and sudden pain with a change of the function of the limb, it is necessary to think of the SLI syndrome and to search targetedly for it. b) In injuries connected with bleeding our first-rate task is the control of this bleeding. For a temporary arrest of the bleeding it is necessary to prefer more physiological methods sparing collateral circulation to the still most used tourniquet. For this purpose a new device for temporary hemostasis called Hemostop has proved itself, designed by the author and attested both experimentally and clinically, protected as a Czechoslovak patent. From surgical measures have acquitted themselves from this viewpoint the insertion of vascular clamp, ligature of the vessel or its temporary cannulation. c) To set the diagnosis of SLI, it usually suffices a careful anamnesis and clinical examination, advantageous is the investigation by ultrasound. The angiography because of time consumption should be used only in indicated cases. d) The time factor--"race against the time"--has to be always borne on our mind. It is necessary to achieve the recovery of blood circulation in the limb up to 6 or at the latest up to 10 hours from the onset of injury or closure. e) For shortening of the period of tissue hypoxia it is of advantage to use the temporary cannulation of injured vessels. This should be used always, whenever because of any reasons, it is not possible to execute the final reconstructive operation up to 10 hours since the injury, e. g. in polytraumatism, transport difficulties and the like. f) In isolated vascular injuries without bleeding (about 45%) and in all non-traumatic SLI the patients must be efficiently heparinized (i. v. administration, at best by infusion) to prevent the growth of the distal thrombus. g) Final vascular reconstruction should be performed only by erudited surgeons, always with thromboctomy and in protected coagulum. Optimal reconstructive performance should be chosen: for embolism the thromboembolectomy, for acute thrombosis usually the bypassing the afflicted vascular portion by the graft, in injuries appears as the optimal reconstructive measure the anastomosis end to end. At the simultaneous or isolated lesion of the stem vein, we must always try to reconstruct it.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1759113 TI - Gastritis, peptic ulcer and gastric cancer. PMID- 1759114 TI - The story of gastritis. PMID- 1759115 TI - Dyspeptic complaints, diet, gastric mucosa and Helicobacter pylori among an Estonian urban population. AB - A representative sample of an adult population, earlier examined by gastroscopic biopsy, was subjected to correlation and regression analyses to quantitate the influences of different factors on the development of three dyspeptic complaints. In this study a large part of the complaints were incriminated by the subjects to poor tolerance of certain foods and/or beverages. According to the results of formal analysis, the state of the corpus and antral mucosa and the presence of Helicobacter pylori play only an accompanying role in some regression models. PMID- 1759116 TI - Alpha 1-antitrypsin allo- and phenotypes in gastric and duodenal ulcer. AB - Serum alpha 1-antitrypsin (A1AT) allo- and phenotypes (including M1, M2 and M3 alleles) were studied in 99 patients with gastric ulcer (GU) and 56 patients with duodenal ulcer (DU) using agarose isoelectric focusing. The results were compared with the A1AT data of a random population sample of similar genetic background (1422 persons). An increase in M2 allotype and M1M2 phenotype as well as a decrease in Z allotype of A1AT was seen in GU in comparison to DU and the random population. There were no particular clinical features which would distinguish patients with M2 allotype from the remainder of the GU group. However, a trend toward elevated serum pepsinogen I and II levels in patients with M2 allotype was seen. When the pepsinogen levels were compared in the GU patient groups with and without M2 allotype, matched between themselves by the state of the gastric mucosa, a statistically significant difference was revealed between pepsinogen II levels in these two groups. No associations were found between DU and any of the A1AT phenotypes. PMID- 1759117 TI - Serum pepsinogen I and serum gastrin in the screening of severe atrophic corpus gastritis. AB - The possibilities to screen atrophic corpus gastritis with serum pepsinogen I (S PGI) and serum gastrin (S-gastrin) concentrations have been studied in 774 subjects: 71 index subjects selected from a general population at random, 353 of their first-degree relatives, 276 first-degree relatives of patients with gastric cancer, 53 patients with pernicious anaemia, and 21 of their relatives. Discrimination function analysis was calculated from members of random and gastric carcinoma families. S-PGI less than 30 ng/ml had a high sensitivity for severe diffuse atrophic corpus gastritis (SDAG) alone (89.5%) and SDAG + severe patchy atrophic corpus gastritis (SPAG) (89.1%). Respective figures for specificity were 91.5% and 94.8%. The discriminatory power of S-PGI less than 30 ng/ml and S-PGI less than 25 ng/ml was of the same order. The sensitivity of low S-PGI decreased sharply in detection of slighter forms of atrophic corpus gastritis. The sensitivity of S-gastrin greater than 100 pmol/l to discriminate SDAG was 57.9% and SDAG+SPAG 58.7%. Respective figures for specificity were 90.2% and 92.2%. Diffuse and patchy atrophic changes behaved similarly regarding S-PGI and S-gastrin mean concentrations. Accordingly, the biopsy specimen with the severest atrophic changes indicates the degree of atrophy, which associates closely with the changes in S-PGI and S-gastrin. In conclusion, severe atrophic (diffuse or patchy) corpus gastritis may be screened from a general population with high sensitivity and specificity by low S-PGI less than 30 ng/ml, whereas an increased level of S-gastrin is too insensitive for this. PMID- 1759118 TI - Autoimmune reactions to gastric mucosa in chronic gastritis: a review. AB - The main results of two-decade co-operation between Tartu University, Estonia, and the University of Helsinki, Oulu and Tampere in Finland on immunology of chronic gastritis are presented. These results include data on cell-mediated and humoral immunity to autoantigens from gastric antrum and corpus mucosa in chronic gastritis, gastric ulcer, gastric carcinoma and other gastric diseases, as well as in random samples from two populations. PMID- 1759119 TI - Serum pepsinogen I and serum gastrin in the screening of atrophic pangastritis with high risk of gastric cancer. AB - Serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) were examined in the screening of three types of atrophic gastritis with inherent high risk of gastric cancer: in 102 cases with severe atrophic corpus gastritis (SACG), in 5 cases with severe atrophic antrum gastritis (SAAG), and in 15 cases with severe atrophic pangastritis (SAPG) (atrophy both in corpus and in antrum) found among 916 subjects from three family series (265 from gastric cancer families, 425 from randomly selected control families and 226 from pernicious anaemia families). There is no way to screen directly atrophic gastritis restricted to the antral mucosa. In pangastritis atrophy of antral glands causes a failure of the hypergastrinemic reaction of achlorhydria. The combination of S-PGI less than 25 micrograms/l + S-gastrin less than 200 pmol/l detected 80.0% of our cases with SAPG, and only 17 subjects of 794 (2.1%) were false positives i.e. who had not advanced atrophic gastritis. The risk of gastric cancer may be significantly higher in SAPG than in SACG. The estimated prevalence of SAPG was 3% in random family members over 60 years. The combination of S-PGI and S-gastrin is recommended when the cost/benefit ratio in the screening program of gastric cancer is considered and people from a general population are selected for endoscopic studies. PMID- 1759120 TI - Helicobacter pylori in dyspeptic patients: quantitative association with severity of gastritis, intragastric pH, and serum gastrin concentration. AB - The relationship between different features of gastric mucosal inflammation, intragastric pH and serum gastrin concentration and the distribution and quantity of Helicobacter pylori was studied in a series of 107 dyspepsia patients. H. pylori was identified in 62 cases (59%), and its presence was associated with increased amounts of mononuclear inflammatory cells and neutrophilic and eosinophilic leucocytes in both the antrum and the corpus. The number of H. pylori in the antral mucosa was significantly associated with the quantity of mononuclear inflammatory cells. It was also associated with glandular atrophy in antral mucosa, so that slight and moderate glandular atrophy were significantly more common in cases with abundant H. pylori. Intragastric pH and serum gastrin concentration were inversely related to the number of H. pylori in both the antral and corpus mucosa. H. pylori positive patients were also divided into groups according to proportions of H. pylori in the antral and corpus mucosa. In 5 of these patients (8%) the bacteria were present only in the corpus, and this group had a significantly more pronounced degree of glandular atrophy in the corpus mucosa, higher intragastric pH and a higher serum gastrin concentration than the other H. pylori positive patients. The other patients with a higher corpus H. pylori than antral H. pylori score (n = 25; 34%) also had a significantly higher intragastric pH and serum gastrin concentration than those with a corpus H. pylori score lower than or equal to the antral score, while the latter had more severe inflammation in the antral mucosa and a lower intragastric pH and serum gastrin concentration. The results suggest that inflammation in the antrum forms a favourable environment for H. pylori, while atrophy of the corpus glands, being connected with increased pH, leads to a diminished amount of H. pylori. They thus support the view that proliferation of H. pylori is dependent on acid produced by the corpus mucosa. PMID- 1759121 TI - Chronic gastritis: progression of inflammation and atrophy in a six-year endoscopic follow-up of a random sample of 142 Estonian urban subjects. AB - To study the prevalence and course of chronic gastritis (CG), 142 adult subjects collected at random from an Estonian urban area were endoscopically and bioptically examined at a six-year interval. The histology of the antral and corpus mucosae was evaluated by grading gastritis without ("superficial gastritis"; SG) and with atrophy ("atrophic gastritis"; AG) into mild, moderate and severe categories. A total of 135 (95%) and 139 (98%) subjects showed CG in the 1st and 2nd examinations, respectively. The CG healed in one subjects (0.7%), and in 5 out of 7 subjects with normal stomach in the 1st examination the CG started during the follow-up. No change in the severity of CG was seen in 24% of subjects with gastritis in the 1st examination. The main trend of CG was a slow, "one-step progression" in severity of inflammation and appearance of atrophy and intestinal metaplasia. Inflammation progressed significantly, especially in the young age groups and in the antrum in particular. The prevalence of AG increased linearly with age in corpus (mean annual risk 1.25%). Parietal cell antibodies (PCA) were found in 2 subjects in the 1st examination, and a further 2 subjects developed these antibodies later. Three of four PCA-positive subjects belonged to a subgroup of 8 elderly subjects who had corpus AG at both examinations and who also showed normal or normalizing mucosa in the antrum. It is concluded that CG is a slowly progressive disease advancing with time and, once started, rarely healing spontaneously. PMID- 1759122 TI - Grade of Helicobacter pylori colonisation in relation to gastritis: a six-year population-based follow-up study. AB - The prevalence and density of Helicobacter pylori (HP) colonisation was assessed twice, with an interval of six years from antral and corpus biopsies from a randomly collected Estonian urban population sample. Positive HP colonisation was found in either at 1st or 2nd or in both examinations in 85 out of 86 subjects in whom gastritis without atrophy (chronic inflammation without atrophic changes, SG) either developed or remained during the follow-up at the SG level. There was a clear intraindividual tendency to keep the grade of HP colonisation at an unchanged level during the follow-up: the hypothesis of random variation of HP colonisation during follow-up could be statistically rejected. Close to half of the subjects had at both examinations an identical grade of HP colonisation in the antral or corpus mucosa. Distinct changes in HP colonisation were observed in three instances: (1) the appearance of HP colonisation occurred concomitantly with appearance of gastritis; (2) the development of antrum atrophic gastritis (AG) occurred with concomitant diminution and eventual disappearance of HP in the antral side, and (3) normalization of antral mucosa occurred with persistence of corpus AG with concomitant disappearance of HP colonisation at both sites of the stomach mucosa. The grade of HP colonisation increased with increase in severity of SG and decreased with the progression of AG changes. In the antrum at the SG level a distinct increase was seen both in the grade of HP colonisation and in the severity of SG up to middle age, but in the corpus mucosa only HP colonisation but no SG progression was seen in the younger age-groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759123 TI - Characteristics of gastric mucosa which precede occurrence of gastric malignancy: results of long-term follow-up of three family samples. AB - The aim of the study was to evaluate what family characteristics and what morphological, functional and immunological changes of the gastric mucosa precede the development of gastric malignancy in a follow-up of 11-14 years. The material consisted of 301 first-degree relatives of gastric carcinoma patients, 183 relatives of pernicious anaemia patients, and of 358 control relatives of probands computer matched from the general population by age and sex for the carcinoma probands. All subjects were endoscopically examined in 1973-1976 and followed up to the end of 1987. According to cancer registry data, 11 cases of malignant gastric tumours (9 carcinomas, one carcinoid tumour and one anaplastic tumour with suspicion of Hodgkin's disease) had been diagnosed during the follow up: 6 belonged to gastric carcinoma, 2 to pernicious anaemia and 3 to control families. The occurrence of malignancy was significantly related to the presence of advanced gastritis with atrophy and of intestinal metaplasia before the start of the follow-up. In relatives with achlorhydria and low serum pepsinogen I levels the incidence of malignancy did not significantly differ from that in controls of similar age and sex distribution. The risk of getting malignancy was about four-fold in female members of gastric carcinoma and pernicious anaemia families but was not increased in control families. The risk was increased only in female members and concerned only gastric malignancy being the expected one or even lower than the expected in regard to malignancies of other location. PMID- 1759124 TI - Enrichment of combined antral and corpus atrophic gastritis ("combined AG") in sibs of gastric carcinoma patients. AB - The occurrence of different combinations of antral and corpus atrophic gastritis (AG) was studied in 127 sibs and 159 children of 73 gastric carcinoma patients. Seventy-three control probands, age- and sex-matched for the carcinoma probands, and their 379 first-degree relatives were used as controls. Sibs of gastric carcinoma patients revealed a significant enrichment of AG affecting simultaneously both antrum and corpus (combined AG), while no such enrichment could be demonstrated in children, who behaved on the whole similarly to the controls. In addition, sibs of gastric carcinoma patients showed a significant aggregation of combined AG also when compared with children of similar age. This suggests that genetic factors in addition to environmental ones participate in the accumulation of combined AG in sibs. The lack of phenotype AB in children excludes the possibility of dominant Mendelian inheritance, but leaves the possibility of a recessive autosomal or multigenetic inheritance. The enrichment of combined AG in sibs of gastric carcinoma patients could be one of the factors involved in the increased liability of close relatives of gastric carcinoma patients to contract gastric malignancy. PMID- 1759125 TI - Chronic gastritis profiles in sibs of probands calculated to carry a highly increased risk of gastric carcinoma. AB - Of 1161 subjects consisting of 4 family samples (gastric carcinoma patient relatives, pernicious anaemia, duodenal ulcer and control families) 18 subjects representing 17 families had distinct atrophic changes in the gastric mucosa that were considered on the basis of risk calculations to carry an at least 7-fold risk to develop gastric carcinoma. Twelve of these 18 subjects could be used as probands and their 41 sibs were subjected to a closer statistical analysis. Sibs of probands having a very high relative risk of gastric carcinoma (18-fold or more) differed markedly from the general population. All sibs had some form of atrophic gastritis and there was a significantly higher than expected prevalence of subjects with severe corpus mucosal atrophy. It is concluded that sibs of subjects with severe atrophic changes may carry an increased risk of gastric malignancy. PMID- 1759126 TI - Young onset peptic ulcer disease and non-ulcer dyspepsia are separate entities. AB - The characteristics of peptic ulcer and non-ulcer dyspepsia in young men were studied in 202 consecutive conscripts who attended Central Military Hospital in Helsinki because of long-standing upper abdominal complaints. Active peptic ulceration (APU) was found in 48 patients, inactive peptic ulcer disease (IPU) was diagnosed in 77 patients, non-ulcer dyspepsia (NUD) was diagnosed in 52 patients. In 25 cases the reason for symptoms was another disease, and these patients were excluded from the study. A control series (CON) consisted of 30 symptomless healthy young male volunteers. The likelihood of discriminating between peptic ulcer disease and non-ulcer dyspepsia in a young male patient with dyspepsia are indicated by odds ratios (OR) and its 95% confidence limits (CL 95). Active peptic ulcer disease differs from NUD, e.g., by 1) presence of antrum gastritis, OR 41.5 (CL 95: 10.1-171), 2) Helicobacter pylori in the gastric mucosa, OR 31.0 (7.4-130), 3) Lewisa+ phenotype, OR 8.9 (1.7-45.4), 4) serum pepsinogen I (S-PGI) greater than 100 micrograms/l, OR 4.6 (1.7-12.4), 5) non secretor status, OR 4.3 (1.6-11.6), and 6) O-blood group, OR 3.0 (1.2-7.7). In conclusion, the status of gastroduodenal mucosa, gastric secretion pattern and distribution of some genetic markers in patient series indicate that young onset peptic ulcer and non-ulcer dyspepsia are two separate entities. Helicobacter positive antrum gastritis is the best determinant of ulcer risk, but also high S PGI, Lewisa+ phenotype, non-secretor status and O-blood group are signs of increased risk of peptic ulcer. PMID- 1759127 TI - Estonian traditions in the study of chronic gastritis. PMID- 1759128 TI - Helicobacter pylori and duodenal ulcer. A study of duodenal ulcer patients and their first-degree relatives. AB - Out of 59 duodenal ulcer (DU) probands and their 199 first-degree relatives Giemsa-staining for the determination of Helicobacter pylori (HP) was performed in 51 probands and 155 relatives. Controls were matched by age and sex from a family sample representing the same geographical area. In all, 155 controls were found for the probands and relatives. The occurrence and score of HP density showed an excellent correlation with morphology of the mucosa, signs of acute inflammation and presence of gastric metaplasia in the duodenal bulb. The prevalence of HP was 94% in DU probands and significantly higher than in their relatives and controls. In sibs of DU probands the prevalence of HP (64%) was also significantly higher than in controls (51%) obviously due to the presence of a subgroup of sibs with signs of active or past duodenal ulcer disease, which show higher than expected prevalence of HP, and of acid hypersecretion and high levels of serum pepsinogen I (PG I). Peak acid output (PAO), serum pepsinogen I and II and fasting serum gastrin levels were in relatives without atrophy higher in HP positive than negative cases but significant differences were present only with regard to the pepsinogens. The occurrence of HP positivity as well as of high PAO and pepsinogen levels might be considered risk factors of DU disease in close relatives of DU probands. On the other hand, the significance of HP positivity as cause of abdominal complaints is doubtful, in view of the complete lack of correlation between HP and morphology and complaints in the present study. PMID- 1759129 TI - Functional characteristics of duodenal ulcer patients and their first-degree relatives. AB - The behaviour of acid secretion, serum pepsinogen I and II (PG I and PG II) and morphology of the gastric mucosa were analyzed in 59 duodenal ulcer probands (DU probands), their 199 first-degree relatives and 228 control subjects. DU probands had as a rule antral gastritis with normal or slightly altered corpus mucosa, and higher mean peak acid output (PAO), PG I and II levels than their relatives and controls. Sibs of DU probands differed from their controls mainly with regard to morphology which showed features characteristic of DU probands, i.e. antral gastritis with normal or slightly altered corpus mucosa. Moreover, high PAO levels were found highly significantly more often in sibs of DU probands (13%) than in controls (6%). Likewise, the prevalence of endoscopic signs of active or past duodenal ulcer were present in sibs highly significantly more often than in controls and they accumulated in the subgroup of sibs with high PAO or PG I levels. It seems probable that the occurrence of high PAO and PG I levels in sibs of DU probands can be considered as signs of increased liability to duodenal ulcer. PAO and PG I were as expected significantly higher in male than in female probands, relatives and controls. Exclusion of cases of corpus gastritis decreased the levels but the sex difference persisted. PAO, PG I and II revealed a significant increase of the levels in middle age followed in older age in case of PAO and PG I by a significant decrease. The decrease was abolished when the cases of corpus gastritis were excluded suggesting an effect of gastritis. However, the earlier increase of the levels remained virtually unaffected although there was a uniform decrease of the mean values. This suggests the participation of factors unrelated to gastritis. The nature of the factors remains unknown, but literature data and data derived from our recent study suggest involvement of anatomical factors such as an increase in the size of acid and PG I secreting area. PMID- 1759130 TI - Helicobacter pylori and chronic gastritis: an increased risk of peptic ulcer? A review. PMID- 1759131 TI - Increase of serum pepsinogen I with age in females with normal gastric mucosa but not in males, possibly due to increase in acid-pepsin secreting area. AB - The mean pepsinogen I (PG I) level in a Finnish family sample was different in males and females and the difference was statistically significant. After exclusion of subjects with gastritis there remained 67 females and 68 males with morphologically completely normal antral and corpus mucosa. In females there was a significant increase of PG I with advancing age, the regression coefficient being 0.37 and statistically significant (p less than 0.01). In males no such increase was found, and individual cases revealed an almost random distribution with age. A similar increase with age has been noted in gastric acid output in females but not in males. Assuming that there is a linear relationship between PG I levels and the total chief cell mass, the PG I level would be determined by three main variables: thickness of the glandular layer, density of chief cells, and area occupied by chief cells. Of these variables the thickness and chief cell density showed neither in females nor in males any statistically significant increase with age, leaving the area as the variable which would account for the increase of PG I. PMID- 1759132 TI - Grade of Helicobacter pylori colonisation, chronic gastritis and relative risks of contracting high gastric ulcers: a seven-year follow-up. AB - A series of 38 patients with high gastric ulcer (GU) was examined twice a seven year interval. One-third of the patients had an active ulcer at the second examination. Chronic gastritis was evaluated, and the level of Helicobacter pylori (HP) colonisation assessed semiquantitatively. The results were compared with age and sex matched non-ulcer controls. The GU series differed from the controls in having a higher degree of HP colonisation in gastric mucosa. The relative risks (RR) in predicting high GU connected with high HP colonisation were significantly elevated, both in the antrum (RR = 6.0-4.8) and in the corpus (RR 5.0-4.4), and still higher when combined HP colonisation values were used (RR 9.5-7.1). The persistence of active ulcer (GU+) was associated with a very high level of HP colonisation, with absence of corpus atrophic gastritis at the first examination and with young patients. Half of the GU+ patients had the maximum grade of combined HP colonisation in both examinations. The study indicates that the presence of HP infection as well as the level of HP colonisation are of importance in both the development and chronicity of peptic GU disease. PMID- 1759133 TI - What fraction of hospital ulcer patients is eligible for prospective drug trials? AB - Data of all 397 gastric ulcer patients diagnosed and treated at Jorvi Hospital, Finland, during 1980-1984 were collected and the outcome followed up for 5-7 years. The commonly used exclusion criteria of prospective drug trials were applied to this series. Only 29% of patients would have been eligible for a trial. The excluded patients were older, their ulcer was larger and more proximally located. Nearly all major complications of gastric ulcer disease leading to surgery (bleeding, perforation, obstruction) and deaths due to gastric ulcer disease appeared in the excluded group. Exclusion criteria may profoundly affect the selection of patients and the results. When many patients are excluded the applicability of results to the whole material is questionable. PMID- 1759134 TI - Long-term effect of vagotomy on gastric mucosa and Helicobacter pylori in duodenal ulcer patients. AB - The purpose of the study was to evaluate the long-term effects of vagotomy on the morphological status and Helicobacter pylori infestation of the gastric mucosa. Endoscopy with biopsies (2 from antrum and 2 from corpus) was performed in 317 patients on whom vagotomy had been performed on an average 8 years earlier. The success of the vagotomy was estimated by the endoscopic Congo Red technique in 270 cases. Non-operated 187 duodenal ulcer patients were examined endoscopically and bioptically in a similar way and used as a reference series. Helicobacter pylori (HP) was determined by Giemsa staining of biopsy specimens in both series. In non-operated dudoenal ulcer patients, gastritis and HP behaved as expected from the data in literature: antral gastritis was present in nearly all cases (96%), while the corpus mucosa was normal or the process was retarded at the stage of superficial gastritis (76%) and atrophic changes were virtually lacking (1%). On the basis of the Congo Red test the vagotomized patients were separated into two groups: successfully operated, i.e., complete vagotomy, and incomplete vagotomy groups. The results of the examinations were independent of the kind of vagotomy performed, but related significantly to its completeness. The incomplete and complete groups differed significantly. The prevalence of atrophic changes (29%) in the corpus was significantly higher and that of superficial gastritis (69%) lower in the complete than in the incomplete vagotomy group, in which the prevalences were 12% and 85%, respectively. Likewise the prevalence and density of HP was lower in the complete vagotomy group but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759135 TI - Helicobacter pylori: histological and serological study on gastric and duodenal ulcer patients in Estonia. AB - We have examined the occurrence of Helicobacter pylori (HP) infection in 86 Estonian gastric ulcer (GU) and 25 duodenal ulcer (DU) patients. Diagnosis of the HP infection was made histologically (modified Giemsa) from gastric biopsy specimens, and serologically by parallel use of two enzyme-linked immunosorbent assays for IgG antibodies to HP in patient sera. The infection was diagnosed simultaneously by all three methods in 84% of the GU and 84% of the DU patients. The infection was revealed histologically in 88% of the GU and 92% of the DU patients, and serologically by either of the two methods in 94% and 92% of the GU and DU patients, respectively. HP infection was absent by all three methods in one GU patient only, this patient being the only subject who showed normal gastric mucosa in conventional histology. These observations show that HP infection is very common in patients with peptic ulcer in Estonia. In addition, the findings suggest that the serological assays will find a small proportion (15%) of ulcer patients with antibodies against HP but no histologically detectable bacteria. PMID- 1759136 TI - Argyrophil cell hyperplasia associated with chronic corpus gastritis in gastric ulcer disease. AB - Argyrophil cell (AC) hyperplasia in corpus mucosa was investigated in 53 patients with chronic gastric ulcer disease not previously treated with antisecretory drugs. Mucosal biopsies were taken stepwise from the posterior wall in the corpus area of the stomach. Of 117 biopsy sites, 28 showed gastritis without atrophy, 85 showed chronic atrophic gastritis of varying degrees while 4 biopsies showed a normal mucosa. About one third (38%) showed a normal AC pattern. Of the remaining two thirds (62%), 45% had simple AC hyperplasia, 18% had linear and 37% had micronodular AC hyperplasia. A strong association was found between focal (linear/micronodular) AC hyperplasia and chronic atrophic gastritis. It is concluded that focal AC hyperplasia is a common phenomenon in gastric ulcer patients and is inherently related to the spontaneous development of atrophy in the corpus mucosa of these patients. PMID- 1759137 TI - Helicobacter pylori and gastritis in children with abdominal complaints. AB - Gastroscopy with biopsies was performed in 178 children with upper abdominal pain. Of them 109 (61%) had gastritis and 104 (58%) Helicobacter pylori (HP) in antrum and/or corpus. Gastritis consisted in most cases (87% of antral and 86% of corpus gastritis) of mild superficial round cell infiltration. Mucosal atrophy was not found. Accumulation of granulocytes was present in 43 patients and lymphonoduli were found in 33 patients, usually in connection with gastritis. Gastritis affected only the antrum in 18%, only the corpus in 5% and both antrum and corpus in 62% of the cases of gastritis. There was a good correlation between morphology and bacteriology in the antrum and a satisfactory one in the corpus. However, in some cases gastritis was present without bacteria and in some cases a normal mucosa was associated with bacteria. Gastritis and HP prevalences showed a general increasing trend with age, but significances were with one exception lacking. It is tentatively concluded that gastritis begins in childhood as a slight and chronic superficial infiltration affecting usually antrum and corpus simultaneously. In the majority of cases gastritis is associated with HP infection, which seems to start the process. It is possible that the HP-related gastritis is a common cause of abdominal complaints in children; however, convincing evidence is lacking. PMID- 1759138 TI - Parental grief following the death of an infant--a follow-up over one year. AB - The course of parental bereavement during the first year following an infant's death was investigated. Also, the differences in mothers' and fathers' reactions, the differences according to the mothers' occupational role, and the similarities in couples' reactions were studied. From a total sample of 59 families, 13 families answered their questionnaires at all three time points (1, 6 and 13 months), 22 families responded at two time points, and 37 families responded at some point following the loss. Measures relating to anxiety, depression, bodily discomfort, general well being and impact of event were used at the three time points. The results showed that grief, as measured by the different inventories, decreased over time. The decrease was most evident from 6 to 13 months, and most prominent in women. A considerable number of the parents were still actively dealing with the loss all through the first year of bereavement. In most couples the mother reported most distress. Mothers were significantly more depressed than fathers at all time points, and mothers also had significantly higher anxiety and lower general health at 1 and 13 months, and intrusive scores of 1 and 6 months. Women at home evidenced more grief at all three time points than women employed outside the home. A high or low score in one spouse was more strongly correlated with a similar score in the other at 1 and 13 months, than at 6 months. The implications for counselling of parents, with special emphasis on the employment situation of the mother, is emphasized. PMID- 1759139 TI - Parental divorce as a factor in children's perception of human relationships: an analysis of human movement responses in the Rorschach test. AB - The subjects were 108 Swedish children between 10 and 12 years old, who constituted a divorce and a non-divorce group of 27 girls and 27 boys each. Rorschach Tests were administered individually and human movement responses were analysed. Non-divorce children perceived more cooperative and fewer hostile interactions than the divorce children. Responses containing figures engaged in hostile interaction were most common among divorce girls, whereas the divorce boys had difficulties in perceiving any interaction whatsoever. The different effect of parental divorce on the ability of girls and boys to develop satisfactory social relationships is discussed. PMID- 1759140 TI - Mood change and marathon running: a pilot study using a Swedish version of the POMS test. AB - Regular exercise is said to have positive effects on mood, especially if the exercise intensity is low to moderate. However, the acute effects resulting from participation in a strenuous competition, such as a marathon race, have been studied less. The present investigation used the Profile of Mood States (POMS) test to measure mood, before and after the 1989 Stockholm Marathon. A total of 106 male runners (mean age 40.0 years), with finishing times between 3h and 3h 45 min participated as subjects. Results showed great changes between pre- and post marathon scores, most of them significant at the p less than 0.001 level. Furthermore, differences between a faster and a slower group of runners were demonstrated with regard to mood states, even though plasma glucose levels were comparable. It is concluded that participation in a marathon race greatly effects mood, mainly in a more negative way than low to moderately intense exercise does. PMID- 1759141 TI - A methodological note concerning long-term effect of treatment. AB - The long-term effect of treatment is defined as the score change produced directly and indirectly by the treatment during and after the treatment interval. Various instances of combinations of short-term effects, attained during the treatment interval, and of long-term effects are presented. Designs for measuring the short-term and long-term effects are sketched, and suggestions are given for distinguishing between these effects in six representative cases. A multiple occasion measurement of the long-term effect is recommended. PMID- 1759142 TI - Facial reactions to facial expressions in subjects high and low in public speaking fear. AB - This study investigated whether subjects high and low in public speaking fear react with different facial electromyographic (EMG) activities when exposed to negative and positive social stimuli. A High-fear and Low-fear group were selected by help of a questionnaire and were exposed to slides of angry and happy faces while facial-EMG from the corrugator and zygomatic muscle regions were measured. The subjects also rated the stimuli on different emotional dimensions. Consistent with earlier research it was found that Low fear subjects reacted with increased corrugator activity to angry faces and increased zygomatic activity to happy faces. The High fear group, on the other hand, did not distinguish between angry and happy faces. Rating data indicated that the High fear group perceived angry faces as being emotionally more negative. The present results are consistent with earlier studies, indicating that the facial-EMG technique is sensitive to detect differential responding among clinical interesting groups, such as people suffering from social fears. PMID- 1759143 TI - Psychophysiological theories on sympathetic nervous system reactivity in the development of essential hypertension. AB - Psychophysiological theories on the development of essential hypertension are reviewed and evaluated. Two interconnected theories that relate behavior to essential hypertension and account for individual differences in susceptibility to disease are the "hyperreactivity" theory and "the symptom specificity" theory. The "hyperreactivity" theory identifies individual differences in autonomic nervous system reactivity as the pathophysiological mechanism and the "symptom specificity" theory suggests that inflexible, stereotypical responding increases the risk to develop hypertension. Based on a literature review, these theories are examined. There exist both case/control and prospective studies on autonomic nervous system reactivity and the development of hypertension. It is concluded that a neurogenically mediated hyperreactivity to stress is a precursor and not an effect of hypertension. Tasks that call for active but not passive coping efforts are more efficient elicitors of reactivity differences between those at high and low risk to develop hypertension in case/control studies. In prospective studies, active tasks may also have a predictive advantage over passive with respect to blood pressure development. In the early phase of hypertension, an increased cardiovascular reactivity is accompanied by increased neuroendocrine activation. In the later phase, heightened reactivity is confined to the cardiovascular system. This does not prove but is consistent with the notion that transient episodes of increased cardiac output translate into essential hypertension by causing vascular hypertrophy. Case/control studies suggest that an increased "symptom specificity", with stereotypical responding across multiple stressors, is independent of cardiovascular reactivity and a precursor of hypertension. The literature lacks prospective studies on the clinical relevance of stereotypical responding. It is suggested that the presence of both hyperreactivity and symptom specificity in a single individual increases the risk to develop essential hypertension. PMID- 1759144 TI - [Laboratory medicine in the area of interest between medicine and science]. AB - The scientific disciplines of laboratory medicine are analyzed from the point of view of history and the philosophy of science. The results of this study are the following: 1. Laboratory medicine is the name of a group of subjects which exist in an interdisciplinary area between medicine and science. 2. Historical development shows that these subjects arose in the 19th century when medicine adopted the "natural scientific method" and became "scientific medicine". 3. Clinical chemistry, as one example of these subjects, is analyzed in detail to understand the thinking process and the scientific method. This subject is, on the one hand, a "theoretical discipline" (like all of the natural sciences) but, on the other hand, it is a typical "practical scientific discipline" (which like clinical medicine is aimed at certain decisions and actions). 4. The disciplines of laboratory medicine have developed typical "professions" mainly because of their application in clinical practice and their commitment to patient care. PMID- 1759145 TI - [The use of laboratory data]. AB - Medical laboratory data are gained by scientific methods. The method-inherent uncertainties always produce an "inexactitude" of varying degree. The physician who uses these data as a support for his decisions should therefore be able to estimate the reliability of the laboratory data; this can be assessed by statistical methods. The most fundamental characteristics of all analytical methods are analytical inaccuracy and analytical imprecision. The limit of detection and the limits of the measuring interval are functions of these figures. A number of illustrations demonstrate the interdependence of analytical performance and of medical significance of laboratory data. Laboratory data, on the other hand, are--to put it simply--used to distinguish diseased from NON diseased individuals. The "diagnostic validity" of a certain test for a certain medical problem is determined by comparing appropriate collectives. The selection of these collectives and the choice of the cut-off value determine diagnostic sensitivity and specificity respectively. From these figures and prevalence (or "pre-test probability"), the predictive values of a positive (or negative) result can be calculated. The significance of the position of the cut-off value and of prevalence is demonstrated by a number of examples. If the results are not given in a binary form (positive/negative) but in different grades (slightly, moderately, strongly elevated/depressed), and if the results of several tests must be judged in a multivariate manner, the number of theoretically possible patterns can become extremely large. Various approaches designed to overcome these problems are discussed. PMID- 1759146 TI - [Immediate diagnosis: what makes sense?]. AB - New techniques for stat-tests (e.g. "dry chemistry") are discussed with respect to their reliability, speed and economy. Based on these factors, a list of stat tests is proposed which appears to meet the needs of the general practitioner's laboratory. The new techniques may also affect hospitals and pharmacies. PMID- 1759147 TI - [Chemical sensors in medical use: ion-selective electrodes, limitations and potentials]. AB - The electrolyte concentrations of potassium and sodium, for example, are routinely analyzed in diluted serum and plasma. In contrast, electrolyte activities are quantified by ISEs directly in undiluted whole blood and plasma and promise to be highly informative. Nevertheless, some drawbacks, such as the interaction between the biological matrix and the ISE surface, limit the accuracy of measurements. A symmetrical measuring arrangement allows one to localize and quantify the known sources of errors. These are minimized by adequate techniques. The membrane composition for sodium selective electrodes is optimized in particular. The interpretation of ISE values as compared to FAES (flame atomic emission spectroscopy) is closely related to the water concentration of the samples. Comparisons between ISE and FAES results obviously allow one to evaluate the water concentration of samples, as is shown by a linear regression plot. PMID- 1759148 TI - [Determination of alcohol dehydrogenase genotype: no correlation between isoenzyme pattern and liver cirrhosis]. AB - Mounting evidence from various fields of research links the oxidation product of alcohol, acetaldehyde, with the development of alcohol abuse-related pathology. One factor governing the production of acetaldehyde is the genetically determined pattern of class I alcohol dehydrogenase isoenzymes, consisting of "fast" beta 2 and gamma 1 and "slow" beta 1 and gamma 2 subunits. Alcoholics carrying the beta 2 and gamma 1 genes might, therefore, be more susceptible to alcohol-related liver disease. To verify this hypothesis we developed a method based on the polymerase chain reaction and restriction enzyme digestion in order to genotype individuals with respect to their alcohol dehydrogenase isoenzyme pattern. In a total of 100 caucasian individuals the following genotypes were determined: beta 1 beta 1, 92; beta 1 beta 2, 8; beta 2 beta 2 0; gamma 1 gamma 1, 38; gamma 1 gamma 2, 51; gamma 2 gamma 2, 11. No statistically significant differences in the distribution of isoenzymes were detectable between alcoholics with liver disease, patients with non-alcohol abuse-related liver disease, patients with rheumatoid arthritis and healthy controls. PMID- 1759149 TI - [Evaluation of enzymatic methods for the determination of plasma sodium and potassium using the Hitachi 747 analytic system]. AB - In the hospital clinical laboratory, plasma potassium and sodium are usually determined by using a flame photometer or ion-selective electrodes, for which special equipment is required. The new enzymatic methods of sodium and potassium can be used as a routine chemical method. We evaluated the new enzymatic methods for the determination of sodium and potassium in human plasma on the Hitachi 747. The sodium and potassium assay kits were purchased from Boehringer Mannheim, Germany. Precision studies were performed using three levels of pool plasma. The coefficients of variation (CV) of sodium and potassium determination were less than 1.0% and less than 2.2% by intraassay and interassay respectively. The recoveries of the assigned values of the ten control sera were 97-102%. Comparisons with results either from flame photometry and from ion-selective electrodes showed no clinically relevant differences for 100 patient samples. Performance of the enzymatic methods for Na+ and K+ is clinically comparable to flame photometry or ion-selective electrodes in the routine clinical chemistry laboratory. PMID- 1759150 TI - [Detection of lysergic acid diethylamide in human urine: elimination, screening and analytical confirmation]. AB - The Coat-A-Count DPC and Roche Abuscreen RIA for LSD were used to search for LSD in urines containing various drugs commonly found in specimens from addicted groups. Elimination of LSD in urine of a volunteer after ingestion of 50 micrograms confirmed that LSD can be detected after 3 days at 0.1 ng/ml cut-off level. Chromatographic conditions were restudied and the full spectrum of trimethylsilyl LSD at 0.125 ng with ion trap GC-MS (ITS40) was shown. PMID- 1759151 TI - [Biliopancreatic bypass and disorders of iron absorption]. AB - Sideropenic anemia is a common long-term complication of surgical bilio pancreatic bypass for morbid obesity, and is frequently resistant to oral iron therapy. To study the pathogenesis of this phenomenon we investigated 7 such patients clinically and biologically, with special emphasis on iron absorption. Our results show that sideropenia, consistently present and frequently complicated by anemia, is due to deficient iron absorption and that this malabsorption is non-selective. Replacement therapy, when indicated, should therefore use the parenteral route. PMID- 1759152 TI - [Telephone duty "AIDS Information" at the Vaudois University Hospital Center: who calls and why?]. AB - From January 1989 to December 1990, 7653 phone calls were answered by the AIDS Hot Line of the Centre Hospitalier Universitaire Vaudois. Most of the calls were from the general public (82%), 12% from health care workers and 6% from HIV infected subjects. The main reasons for calling were information regarding the HIV test (public), scientific inquiries (health care works) and requests for medical or social support (HIV-positive persons). With more than 15 phone calls per day, this hot line fulfils a definite need with respect to the various types of information required. PMID- 1759153 TI - [Nosology and ultrasound findings in porencephaly]. AB - Congenital cerebral defects can be classified into two groups of porencephaly. Agenetic porencephaly results from development disturbances during early neuronal migration and can often be observed in the region of the fissura Sylvii. Encephaloclastic porencephaly, which is relatively rare, is a late prenatal or perinatal vascular lesion due to arterial ischemic stroke or venous thrombosis, and is located in the supply areas of the vessels involved. Cerebral defects can always be detected by ultrasonography. High resolution ultrasonic instruments or magnetic resonance imaging are appropriate means to find out disturbed patterns of gyration pointing to early fetal developmental disturbances. PMID- 1759154 TI - [Transcranial color-coded real time sonography in adults. Part 2: Cerebral hemorrhage and tumors]. AB - We examined three groups of adult patients to evaluate the clinical application of transcranial colour-coded real-time sonography (TCCS): 28 patients suffering from intracerebral haemorrhage, 36 patients with subarachnoid haemorrhage and 38 patients with primary brain tumours. All sonographic examinations were performed through the intact skull. Cerebral haemorrhages were visualised via TCCS as hyperechogenic areas, which were closely correlated in size and location to CT findings. Apart from the imaging of subarachnoid haemorrhages and cerebral vasospasms, TCCS permitted the identification of the angiographically confirmed aneurysms in 76%. Brain tumours were delineated in the vast majority of the patients examined. In this type of pathology TCCS provided additional information on tumour extension and macroscopic appearance. PMID- 1759155 TI - [The transcranial Doppler ultrasound upright posture test for clinical evaluation of cerebral autoregulation]. AB - Description of a TCD test designed for the clinical investigation of cerebral autoregulation. The Doppler shift frequency of the middle cerebral artery is recorded using of a transducer fixed to the patient's head by an elastic ribbon and a ball joint type probe-holder, and on-line digitally analysed to calculate the TCD flow index (signal power times velocity). Blood pressure is measured every 30 seconds at the right index hold at the level of the heart, using a special sphygmomanometer. The patient sits on a foot-stool. After 1.5 minutes of measurement he rises to remain in upright position for another 2 minutes. The flow index normalised to its average over the sitting period quantitatively indicates the evolution of volume flow brought about by the change of the body position. The change in arterial blood pressure is off-line calculated from its periodic measurements. In a pilot study this test has been successfully used in 30 healthy volunteers and 2 patients suffering from orthostatic dysregulation of blood pressure. PMID- 1759156 TI - [Value of color-coded duplex sonography in diagnosis of acute and chronic venous diseases of the lower extremity]. AB - In a prospective study we compared colour duplex ultrasound to venography in 325 patients with clinically suspected acute lower extremity deep vein thrombosis. In 269 cases of proven thrombosis overall sensitivity and specificity of colour duplex ultrasound were 98% and in calf vein thrombosis 96%. Investigations by both methods after fibrinolytic urokinase therapy of phlebothrombosis in 53 patients revealed no significant diagnostic differences between the two methods. In 115 patients with clinically suspected chronic venous insufficiency colour duplex ultrasound allowed to differentiate between occluded, partially recanalised or normal deep veins with or without venous valve incompetence and superficial venous insufficiency. In this study colour duplex ultrasound in diagnosis of acute or chronic lower limb venous disease attained results that were comparable to those obtained by phlebography. PMID- 1759157 TI - [Routine ultrasound diagnosis of the shoulder. A simplified examination procedure]. AB - With increasing use of ultrasonography at the shoulder, a confusing number of transducer positions have been recommended. At the shoulder, however, dynamic examination yields more information than fixed transducer orientations. In our examination routine, the transducer is guided across the shoulder following the shape of a triangle. Orientation is secured by palpable, bony structures. The clinically relevant parts of the rotator cuff and the long biceps tendon are investigated, first medially and laterally in a transverse projection and then longitudinally. Dynamic examination is provided by moving the transducer as well as the shoulder joint. In a time-saving examination routine, all important soft tissue structures of the shoulder are visualized. PMID- 1759158 TI - [Sonographic anatomy of the axilla]. AB - The axilla represents a region of special interest for small-part sonography. It is easy to demonstrate musculocutaneous, osseous, neurovascular and lymphatic structures. Especially in the presence of breast malignomas with lymphatic drainage to the axillary region sonography of the axillary lymphatic tracts and nodes is essential. The examination is performed with a linear 7.5 MHz transducer with the patient in supine position and the arm hyperabducted. The transducer is directed in transversal and sagittal planes and along the axillary vessels. It is of importance to know exactly the complex topographic anatomy of the axilla. The very dominant pectoral muscles serve as guiding structures. In their vicinity one can find some important groups of lymph nodes. The last station of axillary lymph nodes is the apical group situated along the axillary neurovascular bundle. With their typical echo, the head of the humerus and the coracoid-process facilitate the orientation. Ultrasound is now generally available and should always be used as a secondary method of examination, it breast malignomas are present or suspected in mammogramms, since it supplies important clinical information. PMID- 1759159 TI - [Appearance of the femur head epiphysis in healthy children and in children with hip dysplasia]. AB - In a retrospective study we evaluated 4341 sonographic examinations of 1160 healthy children and 209 children with congenital hip dysplasia with special reference to the appearance of the femoral head epiphysis. In healthy children the epiphysis appeared between the first and seventh month. In more than 95% of the children, the epiphysis was sonographically present after the seventh month. In children with congenital hip dysplasia the first appearance of the femoral hip epiphysis had a retardation of one to two months. In most of the healthy children the epiphysis appeared in the fourth month, and after the ninth month in almost all of the normal hip joints the epiphysis is present. In children with normal hip joint configuration and missing femoral head epiphysis at three months, the final ultrasound examination should not be done before the seventh month. Thus, clinically unnecessary ultrasound examination in 6-week intervals can be reduced. PMID- 1759160 TI - [Ultrasound image of the gallbladder fossa after cholecystectomy in the immediate postoperative period]. AB - 70 patients clinically classified as n.a.d. were sonographically examined for evaluation of the gallbladder fossa within two weeks after cholecystectomy. Four marked signs were noted. In 35 patients (50%) we found homogeneous echogenic formations of triangular, band-like, or oval shape in the bed of the gallbladder. In 25 cases (35.7%) inhomogeneous structures were seen. In 6 cases (8.5%) cystic structures resembling the normal gallbladder were seen which were interpreted as representing seromas or liquified haematomas. In 4 patients (5.7%) the bed of the gallbladder was entirely normal. Whether the gallbladder bed was closed by sutures or not, had no statistically significant effect on ultrasound appearance. PMID- 1759161 TI - [Sonographic assessment of gliding characteristics and gliding bed of the Achilles tendon following surgery]. AB - A bilateral comparative ultrasound evaluation of 55 patients 1-10 years after unilateral Achilles tendon rupture showed that glide was reduced by varying degrees in the tendon in a dynamic evaluation. Disturbed tendon glide was often the cause of persistent disability. In the evaluation of the glide characteristics it was helpful to allocate patients to three categories, structural changes in the tendon bed also being taken into consideration. According to this classification, 56% of the Patients had either good or only slightly reduced glide characteristics, whilst 42% demonstrated severe reductions. It was striking that it was not so much alterations in the tendon itself, but rather changes in the tendon bed that had the more deleterious effects on glide characteristics. PMID- 1759162 TI - [Isolated traumatic dislocation of the fibula head. A rare injury in soccer]. AB - The case presented of a rare injury of the left knee joint underlines the necessity for meticulous examination. We report on isolated dislocation of the head of the fibula in a 25-year-old football player; the diagnosis and therapy for this rare injury are presented. PMID- 1759163 TI - [Is arthroscopy always justified in traumatic hemarthrosis of the knee joint?]. AB - Analysis of 100 consecutive arthroscopies in patients with traumatic hemarthrosis of the knee joint demonstrates the importance of arthroscopy in diagnosis and therapy. In 48 cases injuries of the anterior cruciate ligament, isolated and in combination with lesions of other structures, were found. In 47 cases an operation was necessary. In 21 cases the reason for the hemarthrosis was luxation of the patella, in 6 cases with a flake fracture. Isolated lesions of one of the menisci were found in 11 cases and treated arthroscopically in all cases (2 meniscopexies, 1 total meniscectomy , 8 partial meniscectomies). Only in 8 cases unimportant injuries or lesions were found to have caused the hemarthrosis. PMID- 1759164 TI - [Sinus tarsi and canalis tarsi syndromes. A post-traumatic entity]. AB - The posttraumatic sinus tarsi syndrome is a clinical entity induced by supination trauma of the hindfoot. In pathomorphological terms this is due neither to a ligament rupture nor to an osteochondral lesion. Clinically, local pain in the sinus tarsi is associated with pain during supination or pronation, pain during walking, especially on uneven ground, and "giving way" without signs of mechanical instability. A more severe variant of this syndrome, in which the patient complains of pain on the medial aspect of the hindfoot in conjunction with the typical pain of the sinus tarsi syndrome is described. This medial symptom complex has been identified as the "canalis tarsi syndrome". Injection of a steroid and local anaesthetic agent into the tarsal sinus or tarsal canal will relieve the pain if the underlying pathology is that of a tarsi syndrome, depending on which side the injection is given. An arthrogram of the subtalar joint in a patient with a confirmed sinus tarsi syndrome demonstrates a sac-like anterior bulge of the capsule. Performed on a non-pathologic tarsal sinus, this procedure would demonstrate a corrugated appearance of the capsule anteriorly, without this anterior protrusion. At the Medical School in Hanover, 95 patients with a sinus tarsi syndrome were assessed between 1981 and 1989. In all patients a conservative regimen of repeated injections (6 or fewer) of a steroid and local anaesthetic agent into the tarsal sinus was instituted. In addition, 3 of these patients were identified as having a canalis tarsi syndrome, and injections were simultaneously given into their tarsal canals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759165 TI - [Sonographic versus radiological assessment of chronic outer ligament instability of the upper ankle joint]. AB - Chronic instability of the lateral upper ankle joint ligament is usually diagnosed by clinical and radiological examination. For the evaluation of an ultrasound method of testing lateral instability of the ankle joint we carried out a prospective study. We examined 23 adults who were actively engaged in some form of sport (21 male, 2 female, mean age 32 years) and had a preexisting lateral instability of the ankle. The instability was measured in the standard planes using Scheuba's stress apparatus with simultaneous ultrasound monitoring. The ultrasound examination was performed by positioning the 5-MHz applicator on the lateral side of the Achilles tendon, thus defining a plane from which the instability could be measured in both examination planes by observing the deviation between dorsal inferior edge of the tibia and the dorsal border of the talar roll. For the two examination planes, Spearman's rank-correlation coefficient between the radiological and ultrasound methods was 0.83 and 0.92. The sensitivity of the ultrasound method was 0.90, and the specificity was 0.85. Our study showed a good correlation between the two methods. A pathological talar tilt according to radiological criteria was also revealed by ultrasonography. Thus, all the advantages of ultrasound are now available for the evaluation of chronic lateral instability of the ankle joint. PMID- 1759166 TI - [Organization of a bone bank]. AB - The transmission of infectious diseases by allografts from bone banks has led to considerable restrictions on bone transplantations. HIV and hepatitis are considered to be the most dangerous diseases transmitted in this way. To prevent the transmission of any infections, extensive precautions have to be applied when allografts are taken and during their storage. Donors have been checked for infectious diseases at the time of collection and 3 months later. In addition, the donated grafts must be cultured for aerobic and anaerobic bacteria. This elaborate series of tests can only be mastered if the bone bank is tightly organised. The number of available grafts also be increased by sterilisation and the use of demineralised bone matrix. PMID- 1759167 TI - Introduction: autoimmune myelopathies. PMID- 1759168 TI - The biology of pure red cell aplasia. PMID- 1759169 TI - Therapy of pure red cell aplasia. PMID- 1759170 TI - Pure white cell aplasia. PMID- 1759171 TI - Acquired pure amegakaryocytic thrombocytopenic purpura. PMID- 1759172 TI - The pathophysiology of aplastic anemia. AB - No single cause can explain aplastic anemia. Two major factors are involved: An intrinsic derangement of hemopoietic proliferation capacity that is essentially compatible with life, but has to be considered a premalignant condition. This primarily diseased tissue can be destroyed by immune mechanisms in an attempt to achieve self-cure. Therefore, immunosuppressive therapy can mitigate this immune reaction but leaves the patient with a poorly proliferating bone marrow that is prone to late complications. The clinical presentation and course depend on the balance of these two major factors: If the immune reaction is strong, acute severe aplasia occurs, whereas in patients with a weak immune reaction the disease will present itself rather as chronic pancytopenia with myelodysplastic traits. Co-involvement of environmental cells in the disease process is an additional factor. Poor production of hemopoietic growth factors may aggravate aplasia and poor immune competence may allow abnormal clones to proliferate. All these pathophysiological factors are genetically determined. PMID- 1759173 TI - Allogeneic bone marrow transplantation for severe aplastic anemia. PMID- 1759174 TI - Autoimmune myelodysplasias. PMID- 1759175 TI - [Digital projection radiography. 1: Fundamentals of digital image processing]. PMID- 1759176 TI - [Pneumatosis cystoides intestinalis. A possible complication of acute intestinal graft versus host reaction following allogeneic bone marrow transplantation]. PMID- 1759177 TI - [Myelography today]. PMID- 1759178 TI - [An improved CT diagnosis of unclear ureteral processes using the application of air through a percutaneous kidney stoma]. PMID- 1759179 TI - [Diagnostic imaging during the extracorporeal shockwave treatment of gallstones]. PMID- 1759180 TI - Euthanasia: the "good death"! PMID- 1759181 TI - One-stage construction of giant experimental aneurysms in dogs. AB - In an attempt to find safe and effective methods of treating giant intracranial aneurysms, we have developed a one-step construction of giant experimental aneurysms in dogs with a yield of 100% patency of the parent artery and the experimental aneurysm without intraaneurysmal thrombus. Giant aneurysms were produced in the right thrombus. Giant aneurysms were produced in the right common carotid artery of nine mongrel dogs. Key features concerning the procedure were: (1) proximal placement of the aneurysmal neck, (2) 1 cm length as the aneurysmal ostea, and (3) postoperative aspirin therapy. This one-step construction of giant experimental aneurysms in dogs should prove helpful in evaluating a wide variety of treatment modalities of giant aneurysms in the laboratory. It also may be of additional value in investigative studies relative to catheters, balloons, and other similar techniques. PMID- 1759182 TI - Diagnosis and management of gliomatosis cerebri: recent trends. AB - Gliomatosis cerebri (GC) describes a diffuse overgrowth of the neuraxis by neoplastic glial cells with relative preservation of the underlying cytoarchitecture. Ten cases of GC are presented, followed by discussions of its radiological and pathological characteristics. The diagnosis of GC was formerly made only at autopsy. However, recent improvements in imaging and biopsy now allow for antemortem diagnosis. Immunocytochemistry for S-100 protein and glial fibrillary acidic protein (GFAP) in three open biopsies of early primary GC revealed diffuse proliferation of S-100 immunoreactive and GFAP-resistant small astrocytes. Magnetic resonance imaging appears to be the imaging modality of choice. T2-weighted images generally show contiguous high intensity signal in affected areas. Biopsy, either open or stereotactic, remains necessary for antemortem diagnosis. No treatment has proven effective for GC, the prognosis being poor. The authors also review theories of tumorigenesis of GC in an effort to explain its biology. PMID- 1759183 TI - Coagulation changes after an experimental missile wound to the brain in the cat. AB - Platelet studies (total number and platelet aggregation) and coagulation assays (fibrinogen, factor VIII, and anti-thrombin III) were performed on systemic arterial blood of four control and four experimental adult cats that sustained a penetrating missile injury to the brain. Among the brain-wounded, a significant decrease in the total number of platelets and aggregates occurred 120 minutes after injury. Fibrinogen levels decreased significantly in the brain-wounded animals by 240 minutes after injury and continued declining until the end of the 6-hour experiment. No significant changes occurred in factor VIII and antithrombin III levels in wounded as compared with control animals. These results indicate that blood coagulation factors are altered following a missile wound to the brain. These alterations may, occasionally, lead to clinically manifested bleeding disorders, specifically disseminated intravascular coagulation. Thus, early analysis and control of the coagulation system in the brain-wounded patient should be considered to prevent and treat bleeding disorders in the setting of penetrating head injury. PMID- 1759184 TI - Association of vascular compression in trigeminal neuralgia versus other "facial pain syndromes" by magnetic resonance imaging. AB - Magnetic resonance imaging was performed in 13 patients with trigeminal neuralgia and 18 control patients with facial pain of other types. Among trigeminal neuralgia patients, eight (62%) had vessels seen abutting, or immediately adjacent to, the trigeminal nerve on the side of their symptoms. Only three control patients (17%) had such vessels. The proportion of patients having a trigeminal region vessel associated with their symptoms was significantly higher in patients with trigeminal neuralgia than in controls (p = 0.0086). These findings provide evidence supporting the theory that trigeminal neuralgia is associated with vascular compression of the fifth cranial nerve. PMID- 1759185 TI - Limitation of temporary vascular occlusion during aneurysm surgery. Study by intraoperative monitoring of cortical blood flow. AB - The limitations of temporary vascular occlusion during aneurysm surgery as evidenced by the postoperative ischemic symptoms in relation to cerebral blood flow were studied. Six of the 39 cases had postoperative ischemic neurological deficit. When residual cerebral blood flow was below 15 mL/min/100 g, transient symptoms were seen when temporary clipping was for 10-20 minutes. When more than 20 minutes of clipping was required, irreversible deficits were found. Correlations between residual cerebral blood flow, duration of temporary clipping, and postoperative ischemic symptoms were found. The monitoring of cortical cerebral blood flow is an effective means for determining the limits of temporary vascular occlusion. PMID- 1759186 TI - Solitary cerebral metastasis from lung cancer with very long survival: report of two cases and review of the literature. AB - Solitary cerebral metastases from lung cancer are not uncommon clinical events. Whatever treatment is adopted, long-term survival is rare. Very rare indeed are reports of patients surviving the discovery of lung cancer and brain metastasis for 10 years or more. Indeed, only 16 cases have been reported to our knowledge. We report two further cases, stressing the importance of correct clinicopathological staging so that treatment may be conducted in the way most likely to ensure longer and better survival and, pending a therapeutic breakthrough, to increase the number of long-term survivors. PMID- 1759187 TI - A case of coup and contrecoup extradural hematoma. AB - We report an unusual type of a bilateral extradural hematoma: one due to direct injury and another due to the contrecoup effect. The second evolved after the first hematoma was evacuated. PMID- 1759188 TI - Arteriovenous malformations of the vein of Galen: report of three microsurgically treated cases. AB - Three cases of arteriovenous malformations of the vein of Galen were operated on without mortality and morbidity. Postoperative angiography confirmed total occlusion of the fistulas in each case. Microsurgical operation in the parieto occipital region with interhemispheric approach was performed to cut the numerous feeders. The procedure was terminated when the sac was diminished in size with bipolar coagulation and clipped with encircling clips to preserve the flow through the vein of Galen. In spite of the good surgical results, the long-term outcome in the two pediatric patients was discouraging because of mental retardation caused by the arteriovenous malformation itself. PMID- 1759189 TI - Cerebral aneurysms associated with neurofibromatosis. AB - An uncommonly recognized complication of neurofibromatosis (NF) is an angiopathy of the intracranial and extracranial arteries. Most of the previously reported cases have presented as an occlusive process similar to Moyamoya disease. We present our experience over the past 3 years involving three patients with five cerebral aneurysms and associated NF. Four of the aneurysms were intracranial, two being fusiform in nature. Treatment was surgical occlusion and included Selverstone clamping, balloon occlusion, and direct clipping. There appears to be an association between the development of cerebral artery aneurysms and NF, but the pathophysiology of these vascular changes is not fully understood. PMID- 1759190 TI - Proximal clipping and bypass between bilateral vertebral arteries using a radial arterial graft for the treatment of a dissecting aneurysm of the vertebral artery. AB - Proximal clipping has been performed recently as the main surgical treatment for a dissecting aneurysm of the vertebral artery. When there is a contralateral vertebral artery of a smaller size with arteriosclerotic changes, some form of bypass to prevent cerebellar and brain stem infarction is needed in addition to proximal clipping. We treated a 50-year-old man with a ruptured dissecting aneurysm of the left vertebral artery and stenosis at the V3 segment of the right vertebral artery. The caliber of the right vertebral artery was smaller than the left. After an anastomosis between bilateral vertebral arteries using a radial arterial graft, dissecting aneurysm was clipped at the proximal portion of the aneurysm. PMID- 1759191 TI - [The clinical value of air sonography in the diagnosis of meniscus lesions. A prospective study of 50 knee joints]. AB - This paper shows the results of using air as a contrast medium in ultrasonography of the menisci (aerosonography). 100 menisci (50 knees) were examined with aerosonography and in 93 = 93% the findings were proven to be true by subsequent arthroscopy. 6% of the findings were false positive (2 medial menisci and 4 lateral menisci). One false negative finding concerned a lesion at the free inner edge of the lateral meniscus. Not one single lesion of the medial meniscus was totally missed. The sensitivity of aerosonography is 97.8%, the specificity 89.1%. The predictive value is 88%, the accuracy is 93%. Considering the medial meniscus alone the aerosonographic diagnosis proved to be true in 96% (sensitivity for the medial meniscus 100%, specificity 87.5%, predictive value 94.4%, accuracy 96%). 90% of the aerosonographic diagnosis concerning the lateral meniscus were confirmed by arthroscopy (sensitivity for the lateral meniscus 90.9%, specificity 89.1%, predictive value 71.4%, accuracy 90%). PMID- 1759192 TI - [Experience with the management of fresh cruciate ligament rupture in athletes]. AB - Since 1984 we have done over the top repair of the acutely torn anterior cruciate ligament combined with augmentation by McIntosh lateral-substitution over the top procedure with iliotibial band in view of frequent instabilities following simple reconstruction. After treatment by continuous passive motion and early weight bearing is possible. The results at review were good. This method is recommended to avoid the risk of rerupture. PMID- 1759193 TI - [The significance of the activity score in evaluating knee ligament reconstructions]. AB - In a follow-up study of 156 patients after knee ligament reconstruction for chronic instability, the results of subjective Lysholm score grading and of Tegner activity grading were compared. The postoperative Lysholm score averaged 85 +/- 13.2 points, the activity scores 6.9 +/- 0.9 points prior to instability, 1.7 +/- 0.9 points preoperatively and 5.9 +/- 1.2 points postoperatively. 89 patients reached their preinjury activity level, the average improvement through surgery was 4.2 +/- 1.6 points. Non-active patients regularly returned to their original activity-level, competitive athletes were less likely to regain their previous activity. The subjective results of athletes and non-athletes showed no significant differences. The postoperative activity level clearly correlated to subjective grading by the patient. For scoring results after knee ligament surgery, we use the subjective Lysholm score and an activity score based on average German sports activities. PMID- 1759194 TI - [Specific methods of strength training also in rehabilitation]. AB - Until now only minor attention was given to the importance of strength training methods as part of rehabilitation. Even though there are numerous methods in physical therapy which can, under certain limitations, be summed up as a type of strength training, a differentiated use of training methods which are recognized in sport has not been accepted. However, especially the search for a rapid rehabilitation of the body's performance capability brings up the question about effective training methods. In the following paper the physiological conditions are discussed first, on whose basis the motor requirement "strength" has been structured. This results in consequences for the practical training. For each strength component been introduced, practical suggestions for a strength training are given. PMID- 1759195 TI - [Treatment of fresh fibular capsular ligament lesion]. AB - 340 patients with ruptures in the region of the fibular ligaments at the ankle joint could be followed up clinically and by x-ray after an average period of 3.4 years following trauma and treatment. Significantly better treatment results were seen in the group of 246 patients who had primarily been treated by surgery (77% very good to good) than in the group of 94 patients who had been treated conservatively (41.5% very good to good). On the basis of our own follow-up results, the international literature and with particular reference to the experiences collected in sports orthopedics and sports traumatology, it continues to seem imperative to arrive at an individual indication in each case as to whether a rupture of the lateral ligaments at the ankle joint should be treated by surgery or not; the results we have reviewed point to a generally more favorable outcome of surgical treatment than of the conservative approach. PMID- 1759196 TI - [The most common tendon injury in sports--hammer finger. Origin, classification, diagnosis and rational therapy]. AB - The closed rupture of the distal digital extensor tendon at its attachment on the terminal phalanx the so-called mallet finger - is seen very often in ball games ("basketball finger", "baseball finger"). Closed rupture with and without a bony fragment can be distinguished. We demonstrate a rational and anatomy related way of treatment. PMID- 1759197 TI - [Os trigonum syndrome]. AB - The os trigonum is one of the most frequent accessory bones of the foot. It is located dorsal of the talus. Os trigonum syndrome means a typical pain syndrome localized in the back-foot caused by this ossicle. This syndrome occurs mostly in man with sports activities accompanied with intensive stress to different parts of the foot. It can be caused particularly by standing on the toe in the "en pointe-position" in ballet dancers when the flexor hallucis tendon is under maximal tension or by activities accompanied with maximal plan-tarflexion in soccer players for instance. Typical complaints, findings and different therapeutic procedures are demonstrated in two cases. Therapy includes different non-operative methods. Resistance to non-operative procedures is indication for operative therapy. Excision of this ossicle is surgical therapy of first choice. PMID- 1759198 TI - [An unusual case]. PMID- 1759199 TI - [The relationship between the effect of atenolol on the baroreceptor reflex and its hypotensive action in hypertension patients]. AB - A study was made of the influence of atenolol on the sinocarotid and cardiopulmonary baroreceptor reflexes (BR) in patients with essential hypertension. Sinocarotid mechanoreceptors were activated by means of a cervical decompression pressure chamber. The cardiopulmonary BR was tested by changing venous return with the aid of local decompression of the lower limbs. The changes in the hemodynamic parameters were estimated by continuous recording of the mean arterial pressure (AP), tetrapolar rheography, direct manometry arterial pressure (AP), tetrapolar rheography, direct manometry (right atrium), and venous occlusion plethysmography. The drug hypotensive effect was shown to be related to modulation of the sinocarotid BR. It has been demonstrated that there is no relationship between atenolol suppression of the vasoconstrictor cardiopulmonary BR and the drug ability for AP reduction. PMID- 1759200 TI - [Predictors of the efficacy of psychorelaxation therapy in hypertension]. AB - Results of clinical, psychological and psychophysiological examinations of 136 patients with mild essential hypertension indicate that psychorelaxation therapy is more effective in patients with a higher level of BP response to emotional stress and a shorter period of BP recovery after stress. Those patients had a moderate level of anxiety and interpersonal conflicts. Predictors of the efficacy of autogenic training, breathing relaxation training and biofeedback differed. The antihypertensive effect of those methods was associated with various personality traits. PMID- 1759201 TI - [The clinico-echocardiographic characteristics of commissural mitral stenosis]. AB - Overall 200 patients with rheumatic valvular heart disease were examined. Commissural mitral stenosis (CMS) was revealed in 70 patients (35%). At the preliminary examination stage CMS was not detected in 57% of patients, the tone of mitral valve opening could not be heard in 40%, normal configuration of the heart was preserved in 20% of patients according to the roentgenography data. The echocardiographic features of CMS were revealed: the lack of a cupola-shaped diastolic curvature of the mitral cusp in part of patients, an insignificant narrowing of the left venous opening. PMID- 1759202 TI - [The diagnosis of coronary failure in patients with aortic and mitral valve defects]. AB - The incidence of angina pectoris was investigated and the treadmill test was carried out to assess the presence of myocardial ischemia and heart pump function in 238 patients suffering from mitral and aortal heart disease. Comparison with the coronarography readings has demonstrated that the diagnostic value of the painful syndrome in the health status and anamnesis does not exceed 24%. The appearance of an angina pectoris attack in combination with ischemic alterations on the ECG raised the diagnostic value up to 50%. The authors have distinguished a symptom-complex including the development of angina pectoris, appearance of the ischemic signs on the ECG with the integrity of heart pump function, increasing the diagnostic value of the test up to 83-100%. The integrity or insufficiency of heart pump function were shown to allow differentiation between atherosclerotic and relative coronary insufficiency. The conclusion is drawn about the necessity of carrying out the treadmill test according to the program in patients suffering from heart disease with suspected coronary insufficiency. PMID- 1759203 TI - [Kidney involvement in infectious endocarditis (hematuria)]. AB - As many as 113 patients suffering from infectious endocarditis (IE) were placed under observation. Renal damage was discovered in 28 patients (24.7%). Hematuria was the common laboratory sign of renal damage. 15% of patients showed microhematuria, 9.7 had macrohematuria. In 15% of patients with IE, hematuria was due to diffuse glomerulonephritis, in 5.3% to renal infarction, and in 4.4% to focal glomerulonephritis. In 3.5% of patients, the nephrotic syndrome developed at the disease onset, it was attended by hematuria and was thus a cause of erroneous diagnoses. The appearance of hematuria at the IE onset, attesting to involvement of the kidneys into the pathological process, complicates the diagnosis and early treatment institution. Detection of the hematuric syndrome in patients with a verified diagnosis of IE requires specification of the character of renal damage. The latter one contributes to a graver and prognostically unfavourable course of IE. In 2 out of 8 patients with associated IE and renal damage, the death was caused by progressive chronic renal failure. Postmortem examination confirmed mesangioproliferative glomerulonephritis in all the subjects; in 4, it was coupled with renal infarction. 14.1% of the patients manifested complete and 3.5% partial disappearance of hematuria under the influence of adequate antibacterial therapy of IE. PMID- 1759204 TI - [The hemodynamic support of physical loading in patients with mitral valve prolapse]. AB - Bicycle ergometry and echocardiographic studies were carried out in 29 patients aged 17-29 years with first revealed mitral valve prolapse (MVP) without any signs of mitral regurgitation. According to bicycle ergometry, the patients manifested changes in hemodynamics pointing to dysfunction of the cardiovascular system. Echocardiography discovered a reduction of the mass and a rise of the rate of contraction of the circular fibers of the left ventricle, evidence of the myocardial genesis of the hemodynamic changes. Comparison of the findings of bicycle ergometry and echocardiography allowed a conclusion about the necessity of the follow-up of patients with MVP in spite of the high level of threshold load and the lack of the clinical signs of heart failure. PMID- 1759205 TI - [A morphological analysis of the specimens obtained during endomyocardial biopsies in patients with a clinical diagnosis of dilated cardiomyopathy]. AB - The authors summarize experience gained with a study of biopsy specimens obtained on endomyocardial biopsies from 88 patients with a clinical diagnosis of dilated cardiomyopathy. The diagnostic value of the study was equal to 70%. Dilated cardiomyopathy largely masked myocarditis and alcoholic cardiomyopathy which were diagnosed morphologically in 30 and 13% of the patients, respectively. No morphological alterations which would allow one to change the clinical diagnosis of dilated cardiomyopathy were discovered in 26% of cases. It has been shown that endomyocardial biopsy is an important tool of diagnosis. In order to introduce it on a broader scale, it is necessary that quantitative uniform criteria for the diagnosis of endomyocardial diseases, primarily myocarditis, be elaborated. PMID- 1759206 TI - [The clinical importance of the dynamic determination of the serum neopterin level in patients with dilated cardiomyopathy]. AB - Serum neopterin was measured over time (from 3 to 24 months) by RIA in 15 patients with dilated cardiomyopathy. Comparison with the clinical data revealed that the initially normal concentration of neopterin (less than 9 nM/l) was associated with a stable disease course on a long-term observation (group I). The second group with an initially high neopterin concentration showed an objective improvement of the health status together with normalization of the neopterin level. The third group of patients were characterized by an increase of the neopterin level measured over time, coupled with a disease progress. It should be noted that 5 out of 8 patients died. In addition to neopterin measurements, the patients with dilated cardiomyopathy were examined for serum beta-2-microglobulin (beta-2M). Analysis of the data obtained has demonstrated a similar relationship between the level of neopterin and beta-2M and the clinical course of dilated cardiomyopathy. Still, neopterin is a more sensitive marker. Therefore, the data obtained attest to a possibility of the use of serum neopterin as a prognostic marker in patients suffering from dilated cardiomyopathy. PMID- 1759207 TI - [Arterial hypertension and its treatment in the aged]. AB - The rise of arterial pressure in elderly and senile persons reflects morphological alterations in the vessels, the development of sympathetic hyperactivation and adrenoreceptor dysfunction rather than can be referred to compensatory and adaptation reactions of the body. The treatment of patients suffering from arterial hypertension should be aimed at preventing the development of fibrinoid arterial necrosis which may occur because of regular antihypertensive therapy and dyslipidemia correction. PMID- 1759208 TI - [The comparative value of myoglobin determination in patients with different forms of ischemic heart disease]. AB - The hemagglutination test was used to measure the content of myoglobin (MG) in the blood serum in 92 patients suffering from coronary heart disease (myocardial infarction, unstable and stable angina pectoris). The content of MG turned out a safe indicator attesting to acute myocardial infarction. In complications and spreading of necrosis, the MG level was returning to normal slowly. In patients with angina pectoris, the MG level did not on the average differ from control. However, in patients with unstable angina pectoris, there was an increase of the MG content after long-term attacks and in the development of small-focal necroses in the myocardium. PMID- 1759209 TI - [The current concepts of the effect of cardiac glycosides on sinus node function and atrioventricular conductivity]. AB - The clinical aspects of the influence of cardiac glycosides on the sinus node and atrioventricular junction in health and dysfunction are reviewed. It has been shown that digitalis drugs do not produce any effect on sinus node automatism including that in dysfunction. Cardiac glycosides suppress enhanced atrioventricular conduction and do not affect it provided it remains within normal. The mechanisms by which cardiac glycosides may act are discussed: extracardiac, cholinomimetic (in the acute test and direct one) and influencing heart conduction components (when used continuously). PMID- 1759210 TI - [Excessive treatment in the internal disease clinic]. PMID- 1759211 TI - [Recurrent infectious endocarditis]. PMID- 1759212 TI - [Suppurative complications of myocardial infarct]. PMID- 1759213 TI - [A severe course of autoimmune thrombocytopenia and the procedure for its treatment in systemic lupus erythematosus]. AB - The authors describe three comparatively rare cases of extremely severe symptomatic autoimmune thrombocytopenia associated with systemic lupus erythematosus. The use of glucocorticoids in large doses and in two cases of splenectomy turned out ineffective. The next therapeutic measures are suggested in the following succession: glucocorticoids----cytostatic drugs (vincristine)--- splenectomy to be performed only in special cases. PMID- 1759214 TI - [The treatment of supraventricular tachyarrhythmias by the transvenous electrical destruction of the atrioventricular junction of the heart]. PMID- 1759215 TI - [Permanent forms of tachyarrhythmia as the possible cause of the development of the dilated cardiomyopathy syndrome]. AB - To specify a possible role played by rhythm disorders in the development of dilated cardiomyopathy (DCM), 9 patients showing permanent sinus and/or supraventricular tachycardia (since birth or within the first 5 years of life) coupled with ventricular rhythm disorders and 11 patients with an assumed infectious disease onset were examined. It has been established that in supraventricular tachycardia, sinus tachycardia included, patients of the child and juvenile age may develop dysfunction of the left ventricle followed by its dilatation which manifests clinically by DCM. The use of antiarrhythmic (cordarone) in such cases may lead to diminution and even to normalization of the heart size and to amelioration of the hemodynamic parameters. PMID- 1759216 TI - [The use of the phase-image method for noninvasive topical diagnosis in certain forms of heart rhythm disorders]. AB - The authors describe the results of mapping additional conduction pathways in WPW syndrome and ectopic sources of the ventricular rhythm with the aid of phasic images (PI). The mapping data were compared to the readings of 12 ECG leads and to the electrophysiological findings. The mapping with the aid of PI turned out informative in both patients' groups. The PI method demonstrated the possibility of Kent's bundle mapping in latent WPW syndrome. The use of the PI method is suggested to be the first stage in the mapping of Kent's bundle in WPW patients suffering from supraventricular tachycardias as well as of pathological rhythm sources in ventricular tachycardias refractory to drug therapy in patients who are to undergo surgical treatment. PMID- 1759217 TI - [The importance of Holter ECG monitoring in the diagnosis of latent arrhythmias in patients with acute respiratory viral infections]. AB - Altogether 37 patients suffering from influenza and acute respiratory viral infections were examined. In 25 patients, acute infections ran their course in association with coronary heart disease. According to the ECG readings, 15% of the patients had rhythm and conduction disorders. Meanwhile Holter ECG monitoring revealed the above disorders in 70% of the patients afflicted with influenza and acute respiratory viral infections. PMID- 1759218 TI - [Etatsizin efficacy in patients with ventricular tachycardias. The results of intracardiac electrophysiological research]. AB - As many as 30 patients with different pathologies of the cardiovascular system and paroxysms of ventricular tachycardias were examined. According to the ultrasonography data, an ejection fraction was not lower than 35% in all the patients. It has been shown by electrophysiological studies that intravenous injection of ethacizine in a dose of 0.6 +/- 0.1 mg/kg prevented induction of ventricular tachycardia in 66.7% of patients. In 16.7% of patients, the drug exerted an arrhythmogenic effect that showed up by a decrease of the cycle of tachycardia. Oral administration of ethacizine in the daily dose 100 or 150 mg prevented tachycardia induction by endocardial stimulation in 20.8% of patients. The arrhythmogenic effect of the drug was recorded in 12.5% of patients. The action of ethacizine when administered by both routes was accompanied by a significant elongation of the P--Q interval, QRS complex and of the cycle of ventricular tachycardia. Continuous administration of ethacizine in the daily dose 150 mg to patients with a positive antiarrhythmic drug action (according to the electrophysiological data) prevented paroxysms of ventricular tachycardia, with the observation period being 2 to 6.5 years. PMID- 1759219 TI - [The diagnosis and possibilities for the anti-arrhythmia treatment of malignant ventricular disorders of the heart rhythm]. AB - Altogether 130 patients with malignant ventricular disorders of cardiac rhythm were examined to demonstrate a possibility of obtaining the diagnostically significant data with the aid of Holter's monitoring of the ECG in 89.2%, with the aid of bicycle ergometry exercise tests in 72.3%, and by means of an electrophysiological examination of the heart in 82.5% of the above-indicated group of patients. The drug testing with the use of invasive and noninvasive techniques of monitoring the action of antiarrhythmic drugs given per os makes it possible to choose effective therapy on an individual basis. The long-term use of such therapy may prevent ventricular tachycardia relapses and noticeably enhance the patients' survival. Severe organic pathology of the heart associated with a decrease of its pump function seen in the majority of patients with malignant ventricular disorders of cardiac rhythm refractory to pharmacotherapy restricts, in a considerable number of cases, the potentialities of drastic surgical treatment because of the risk of operative death. To improve the disease prognosis of these patients, it is necessary that other methods of nonmedicamentous treatment may be used, requiring a less scope of surgical intervention, such as implantation of a cardioverter-defibrillator. PMID- 1759220 TI - [The outlook for the diagnosis and treatment of cardiovascular diseases]. PMID- 1759221 TI - [A method of choosing maintenance anti-arrhythmia therapy after sinus rhythm restoration in patients with a permanent form of atrial fibrillation]. AB - The authors suggest a new method of choice of the drug (quinidine or cordarone) for the maintenance antiarrhythmic therapy after sinus rhythm recovery in patients with permanent atrial fibrillation, in patients with rheumatic heart disease and coronary heart disease. The method is based on the formalized prediction of the results of cardioversion and on the distinguishing groups with a good and bad prognosis. In the former group, both drugs can be administered, in the latter group, it is desirable that cordarone may be used. PMID- 1759222 TI - [The detection of changes in intra-atrial conductivity (based on enhanced ECG data)]. AB - The 20-fold enhanced ECG (without frequency filtration of the signal) was recorded in 30 normal men aged 18 to 36 years. A study was made of the constancy of the P wave forms on the ECG. The P wave form underwent changes in 8 test subjects: in 5 during breathing retention on expiration and in 3 during superficial breathing. The changes indicated are viewed as a manifestation of intraatrial conduction disorders. It is assumed that the changes in the tone of the autonomic nervous system and myocardial hypoxia may contribute to the detection of latent disorders in the cardiac activity. PMID- 1759223 TI - [The natural course of a complete atrioventricular block]. AB - The natural disease course is analyzed in 311 patients with atrioventricular blockade admitted for surgical treatment to the Leningrad Center of Arrhythmia Surgery and Cardiac Pacing. It has been discovered that, as a rule, Morgagni Adams-Stokes (MAS) attacks do not occur for over 2-3 years after their onset, which determines to a considerable measure the patients: life expectancy. The authors hold that the very first Mas attack which may occur in a patient with atrioventricular blockade is an absolute indication for implantation of a permanent cardiac pacemaker. If the permanent cardiac pacemaker was established, 1-, 3-, 5-, 7- and 8-year survival rates were, respectively, 91.1, 85.8, 77.3, 63.2, and 60.8%. PMID- 1759224 TI - [The variability of the myocardial ischemia indices in stenocardia patients during repeated exercise tests]. PMID- 1759225 TI - [The role of a spasm of the coronary arteries in the pathogenesis of acute myocardial infarct and in the development of sudden coronary death]. AB - Based on the clinical experience and clinicoanatomic correlations, the authors suggest the role of hemorrhage and rupture of atherosclerotic patches in the pathogenesis of sudden coronary death. Proceeding from long-term follow-up studies of patients suffering from CHD, the necessity is substantiated of the regular use of beta-adrenoblockers which significantly reduce the rate of sudden death both in the acute and chronic phases of CHD, particularly in patients with a history of myocardial infarction. Taking into consideration the multifactorial nature of the pathogenesis of acute occlusion of coronary arteries, it is suggested that in addition to the preventive administration of beta adrenoblockers, thrombolytic agents in combination with antiaggregation remedies and calcium antagonists should be prescribed, especially in cases of arterial pressure rises. PMID- 1759226 TI - [The cholesterol content in immune complexes as a marker of coronary and peripheral atherosclerosis]. AB - As many as 107 patients with coronary atherosclerosis, 66 with peripheral atherosclerosis, 27 with unaltered coronary arteries and 30 healthy blood donors were examined. The content of cholesterol in immune complexes was significantly higher in patients with coronary and peripheral atherosclerosis as compared to patients with intact arteries and healthy subjects. The highest content of cholesterol in immune complexes was detected in patients with combined lesions of coronary arteries and arteries of the lower limbs. It exceeded 3.5-5.5-fold the content of cholesterol in immune complexes in the control groups. The accuracy of the diagnosis with the aid of measuring the content of cholesterol in immune complexes in atherosclerosis of any sites was equal to 85%, in peripheral atherosclerosis to 89%, which slightly exceeded the diagnosis accuracy in atherosclerosis of coronary arteries (83%). PMID- 1759227 TI - [The dynamics of the concentrations of immunoglobulins and circulating immune complexes during low-density lipoprotein apheresis in patients with hereditary hypercholesterolemia]. AB - Sessions of-low density lipoproteins (LDL) apheresis using sorbents with mono- and polyclonal antibodies possessing the most selective and specific effect with respect to LDL provoked a less marked decrease of the concentrations of immunoglobulins and circulating immune complexes. This attests to their high selectivity and specificity. Sorbents with dextran sulfate and heparin sepharose exerted a more evident influence on the concentrations of these serum components. However, that was not accompanied by any clinical manifestations of immune deficiency. The use of plasmapheresis brought about a more pronounced lowering of the concentrations of the serum components under study. PMID- 1759228 TI - [Intravascular blood coagulation in patients with ischemic heart disease]. PMID- 1759229 TI - [The circadian rhythms of myoglobin concentrations in the blood serum in acute myocardial infarct and unstable stenocardia]. AB - Patients with acute myocardial infarction and unstable angina pectoris do not demonstrate circadian time organization of myoglobin concentration rhythms. The predominance of ultraradian and infraradian neorhthmostasis is typical of such patients. Determination of myoglobin concentration rhythms in the given patients' group may be helpful in the measurement of the size of the focus of necrosis and prediction of the course and outcome of the diseases under consideration. PMID- 1759230 TI - [Occupational therapy in the rehabilitation of myocardial infarct patients in the convalescence phase]. PMID- 1759231 TI - [The factors determining the efficacy of the rehabilitative treatment of patients who have had a myocardial infarct]. AB - Factors responsible for the efficacy of rehabilitative treatment of patients with a history of myocardial infarction were defined on the basis of the 2-year follow up of 235 patients who suffered myocardial infarction, bicycle ergometry data, studies into intracardiac hemodynamics, oxygen supply in exercise tests, and criteria for the significance of the tetrachoric indicator with regard to the confidence limits. In patients who suffered uncomplicated myocardial infarction, prediction of the decreased work fitness in the long-term period is determined by the presence of angina pectoris and arterial hypertension. It has been established that whether will be lowered in future can be judged from the changes seen in the magnitude of the liminal power and the end diastolic volume of the left ventricle during the first 6 months following myocardial infarction. PMID- 1759232 TI - [The current aspects of the problem of heart rhythm disorders]. PMID- 1759233 TI - [An epidemiological study of ischemic heart disease, vascular brain diseases and their risk factors in an open population of 25- to 64-year olds in Novosibirsk]. AB - To study the incidence of coronary heart disease (CHD), cerebrovascular diseases (CVD), combined pathology (CHD and CVD), and their risk factors such as arterial hypertension (AH), overweight (OW), hypercholesterolemia (HC), and tobacco smoking in the same population, a random representative sample of male and female populations were examined in three districts of Novosibirsk. AH and tobacco smoking were found predominant among men, whereas OW and HC among women. It turned out that almost every fourth person out of the men and almost every second woman suffered from cardiovascular diseases. In the men, the CHD/CVD ratio was 1:1, that in the women, was 1:7. In the men and women, suffering from combined pathology, AH occurred more frequently as compared to those with CHD or CVD alone. OW promoted the development of CVD and combined pathology in women to a greater degree, whereas HC favoured the development of CHD and CVD in men. PMID- 1759234 TI - [The somatotype, blood hormone content and the threshold of taste sensitivity to table salt in young people with arterial hypertension]. PMID- 1759236 TI - The physician's guide to medical waste regulations, Part II. PMID- 1759235 TI - [The specificity of the hypotensive effect of calcium antagonists in hypertension]. AB - The purpose of the study was to define prognostic criteria that determine individual sensitivity to the hypotensive effect of slow calcium channel blockers. After two weeks of placebo therapy 45 patients suffering from essential hypertension underwent an acute pharmacological test (APT) with nifedipine in a dose of 30 mg. Then the patients received monotherapy with nitrendipine in the increasing doses for 12 weeks. The drug effect on the renin-angiotensin aldosterone system and the level of ionized calcium in the blood serum was estimated. In 17 patients who responded to the APT by a decrease of the mean arterial pressure (MAP) by not less than 20%, arterial pressure was corrected with nitrendipine administered in a dose not exceeding 20 mg. 28 patients whose MAP dropped by 10 to 20% in response to the APT required higher drug doses (40 mg). 7 patients in whom the MAP dropped less than 10% were practically refractory to the monotherapy with nitrendipine. A close negative correlation was found between the degree of the MAP lowering in response to the APT during nitrendipine monotherapy and plasma renin activity as well as the concentration of ionized calcium in the blood serum. The low content (less than 1.0 mmol/l) of ionized calcium in the blood serum of patients suffering from essential hypertension appeared the most valuable predictor for the hypotensive effect of the slow calcium channel blockers. PMID- 1759237 TI - Medicaid changes mean higher physician payments. PMID- 1759239 TI - TMA, AMA seek legislative fix for Medicare payment schedule. PMID- 1759238 TI - Sunset review starting soon for medical examiners board. PMID- 1759240 TI - No ifs, ands, or butts. You can help patients quit. PMID- 1759241 TI - HIV-I testing not covered. PMID- 1759242 TI - Theft, murder, and drug warfare: a novel solution. PMID- 1759243 TI - Health risks of adolescent sexual activity are focus of TMA report. PMID- 1759244 TI - TDH report updates diagnosing, treating cholera. PMID- 1759245 TI - Therapeutic approaches to chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia is the most common leukemia in the Western Hemisphere and will increase in prevalence as the population continues to age. Partly because of the advanced age of patients and the often prolonged indolent course of disease, therapy has changed little over the past several decades. The clinical course is highly variable and several clinical features have prognostic value. Until recently, therapeutic approaches have ranged from watchful observation to palliative treatment with an alkylating agent alone or combined with a corticosteroid; however, a number of new chemotherapeutic agents (eg, fludarabine, deoxycoformycin, and chloride-oxyadenosine) have been shown to act effectively against the disease. The availability of effective new agents combined with a better understanding of the biology and prognostic determinants in this disease have sparked recent interest in the optimal management of patients with this increasingly common malignancy. PMID- 1759246 TI - Water fluoridation--more isn't better. PMID- 1759247 TI - Predictive value of family history in detecting hypercholesterolemia in predominantly Hispanic adolescents. AB - Plasma levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were obtained in 110 senior high school students who were predominantly Hispanic. Results were compared with family history of premature coronary heart disease or hypercholesterolemia. The level of high-density lipoprotein cholesterol was significantly lower in Hispanic adolescents than in non-Hispanics (P less than 0.05). A positive family history was found in 22% of the subjects. Only 25% of the students with high levels of total cholesterol had a positive family history. The positive predictive value of family history for a high level of total cholesterol was only 38%. These results suggest that adolescents should be screened for hypercholesterolemia regardless of a positive family history. PMID- 1759248 TI - Blunt rupture of the heart in a child. AB - The spectrum of blunt cardiac trauma ranges from injuries with no actual cellular damage (myocardial concussion) to cardiac chamber rupture. Although blunt injuries to the heart are common and potentially lethal, rupture of a cardiac chamber is rare. This injury should be suspected in any patient who presents with cardiac tamponade after blunt trauma. A child who sustained blunt rupture of the right atrium is presented, and the pathophysiology, diagnosis, and treatment of these injuries are discussed. PMID- 1759249 TI - Burditt appeal unsuccessful, but transfers continue. PMID- 1759250 TI - Bridging troubles. Patient representatives aid physicians, too. PMID- 1759251 TI - Fort Worth action stops sale of pound dogs for biomedical research. PMID- 1759252 TI - Benzodiazepines and triplicate prescriptions: New York's experience. PMID- 1759253 TI - Lyme borreliosis in Texas. AB - Lyme borreliosis is a protean infection caused by B burgdorferi, a recently recognized arthropod-borne spirochete. The disease is generally acquired during warm weather, and its onset is characterized by a skin lesion, EM, and flulike symptoms. Neurologic, cardiac, and/or rheumatologic abnormalities may emerge weeks, months, or years later. In the absence of the pathognomonic skin lesion, determination of antibody response is currently the most practical laboratory aid in diagnosis. However, clinical judgement is necessary for the correct interpretation of laboratory results because false-positive and false-negative results are common. Antibiotics remain the mainstay of therapy. Longer courses of antibiotic therapy than those previously recommended may be needed to obtain a cure, particularly in later stages of the illness. PMID- 1759254 TI - Immediate reconstruction: current status in cancer management. AB - Immediate elective repair of various defects caused by ablative surgery for treatment of cancer is becoming increasingly common. In comparison with delayed reconstruction, immediate reconstruction has the advantage of lower costs and, in most cases, reduced anesthesia risks. Immediate repair is also technically easier in many cases and may provide better results. Furthermore, it often provides patients with a strong psychological boost, allowing them to progress toward total recovery and minimizing the time they must live with disability and deformity. Experience has shown that immediate reconstruction does not increase the risk of cancer recurrence or metastasis. Elective immediate reconstruction has proven useful for defects of the breast, chest wall, mandible, nose, oral cavity, and extremities. Illustrative examples are provided so that the potential benefits of this approach can be more widely appreciated. PMID- 1759255 TI - Point prevalence of tuberculosis among central Americans sheltered in Houston. AB - A study to determine the point prevalence of tuberculosis, as defined by a positive tuberculin skin test, was conducted among the inhabitants of a Central American shelter. The point prevalence was found to be 50% (17/34). This high point prevalence demonstrates the need to test Hispanics who have recently arrived in the United States for tuberculosis. The difficulty in completing evaluations of those with positive skin tests makes tuberculin skin testing ineffective in controlling tuberculosis in this population and setting. To improve control, local, state, and federal health agencies will need to coordinate their efforts and increase the accessibility of health care to populations at high risk. PMID- 1759256 TI - Personal choices--communication among physicians and patients when confronting critical illness. AB - Communication among physicians and patients when confronting life-threatening or terminal illness is often flawed. Medical ethics authorities have suggested the physician or the hospital is responsible to determine a patient's wishes for ongoing therapy; yet, few pragmatic suggestions have been made as to how to fulfill this responsibility. Although advance directives are generally available, they are often misunderstood and rarely used. An educational brochure has been designed to facilitate communication by exposing patients and others to some of the technical and ethical issues that come into focus in the setting of critical illness. The brochure includes a living will. Early experience with this device has been favorable. The hospital ethics committee that developed this brochure believes it can be adapted to other institutions and urges its widespread use. PMID- 1759257 TI - [Adaptation disorders in newborn animals: pathogenesis and therapy. Review article]. AB - The sympathoadrenal system of the neonate is stimulated during parturition and immediately after birth. Endogenous opioid peptides can be regarded as partial catecholamine antagonists. They have an inhibitory action on the respiratory center but may also lead to a redistribution of cerebral blood flow in favour of certain essential brain areas. The acidosis seen in connection with neonatal asphyxia stimulates a further release of catecholamines as well as opioid peptides. The therapeutic approach should lead to a rapid normalisation of respiration. PMID- 1759258 TI - [Clinical case. Young Fleckvieh bull, 6 months old]. PMID- 1759259 TI - [The significance of sheep and goats as carriers of zoonoses in this country]. AB - The significance of sheep and goats in this country in connection with the zoonoses rabies, tick-borne encephalitis, contagious ecthyma, Q-fever, chlamydiosis, brucellosis, campylobacteriosis, echinococcosis and toxoplasmosis is discussed. PMID- 1759260 TI - [Bacteriologic studies of aborted sheep fetuses with special reference to chlamydiae]. AB - A total of 467 tissue specimens recovered from 165 aborted ovine fetuses were examined for chlamydiae microscopically and by means of cell culture. Chlamydiae were detected by microscope in 34 fetuses (20.6%) and by cell culture in 60 fetuses (36.4%). Of the 467 tissue specimens, 51 (10.9%) were microscopically positive, whereas chlamydiae were recovered from 181 specimens (38.8%) using the routine method of BGM cell culture. A total of 87 specimens of fetal organs was tested by the BGM cell culture technique and simultaneously by an enzyme amplified immunoassay to detect chlamydial antigen. Although not as sensitive as cell culture isolation, the ELISA has the advantage of rapidity and of detecting antigen from non-viable chlamydiae in sheep abortion material. PMID- 1759261 TI - [Interferon in sheep]. AB - There is only limited information on sheep interferon available. Recent publications have reported on: 1. an interferon (IFN) alpha subtype, which is secreted by the fetal trophectoderm into the lumen of the uterus between the 10th and 21st day of gestation. It was therefore named ovine trophoblast protein (oTP 1), and is responsible for signalling pregnancy to the ewe via high affinity receptors in the endometrium. It is thought that oTP-1 acts by directly influencing prostaglandin metabolism. 2. the role of lentivirus-induced interferon (LV-IFN) in the pathogenesis of Maedi/Visna. The results indicate that LV-IFN limits viral replication and therefore contributes to virus persistence and is also responsible for a chronic inflammatory process. 3. the mitogen- or antigen-dependent induction of ovine interferon gamma (IFN gamma) and its characterization. PMID- 1759262 TI - [Partial aplasia of the right horn of the uterus in a German Schwarzbund cow. Case report]. PMID- 1759263 TI - [Clinical findings in vitamin D poisoning of swine]. AB - Acute to subacute vitamin D toxicosis is described in two different fattening pig herds. A few days after admixing a new batch of vitamin/mineral-premix most of the fattening hogs developed anorexia, polydipsia and polyuria. Emesis was seen in some of the animals. About two weeks after consumption of the suspected feed two thirds of the pigs had a rough hair coat and a very poor weight gain. Because of the results of haematological and metabolic findings from blood and urine samples of diseased pigs a calcinosis and tubular nephrosis was diagnosed. Patho histological findings of the euthanatized morbid pigs included severe chronic interstitial nephritis, glomerulonephritis and mineralisation of a number of organs. Some of the animals showed degeneration of the myocardium. Feeding two healthy pigs with the incriminated feed the disease was reproduced. PMID- 1759264 TI - [Pteridine pattern in the urine of swine of different breeds and halothane genotypes in relation to nutrition and stress]. AB - Urinary pteridine patterns and creatinine concentrations were determined in pigs of the breeds Pietrain, Deutsche Landrasse and their crossbreds. Also the influence of the halothane genotypes, of different feeding and of treadmill exercise was examined. We conclude that creatinine concentration in pig urine is not a reliable reference parameter for the pteridine excretion. Creatinine values were significantly influenced by breed and feeding. The pteridine pattern of pigs' urine depends on the breed and correlates with other metabolic parameters. Stress is reflected by altered pteridine concentrations. PMID- 1759265 TI - [The current status of avian ophthalmology]. AB - Ocular diseases in birds are very rarely investigated. Increased keeping of often very expensive caged birds makes it necessary for veterinarians in practice to deal with the problems of ornithoophthalmology. Fundamental physiological and anatomic differences between the mammalian and the avian eye, interspecies variables and general problems in handling do not allow a simple transfer of knowledge of mammal ophthalmology to birds. Therefore, it is necessary to find differentiated, species-orientated solutions in investigation as well as suitable treatments of ocular diseases in birds. An update on ornithoophthalmology is given. PMID- 1759266 TI - [Immune intervention in Borna disease]. AB - Borna disease is a naturally occurring meningoencephalomyelitis of sheep and horses. After experimental infection of rats with Borna disease virus a biphasic disease with initial gait disturbances and later paresis and paralysis can be observed. The disease symptoms in these experimental animals resemble those of the natural hosts. The disease is not caused by the infecting virus itself but rather by a CD4+ T cell-mediated immune response. After the pathogenesis had been elucidated new strategies for the therapy of Borna disease by interfering with the immune reaction have been developed. Treatment with immunosuppressive drugs, with monoclonal antibodies directed against certain immune cells and with mediators of the immune reaction resulted in an inhibition or significant reduction of Borna disease symptoms. PMID- 1759267 TI - [The effect of nutrition on the origin of colic (digestive disorders) in horses]. AB - Colics are often initiated by mistakes in feeding inadequate feed quality or quantity or poor feeding technique. The consequences are obstruction, impaction or dysbiosis with increased production of organic acids, gas or toxins. Nutritional anamnesis in patients with colic may give information on the pathogenesis of the disease. PMID- 1759268 TI - [Neonatal isoerythrolysis in newborn foals]. AB - Aetiology, pathogenesis, clinical symptoms, diagnosis, prophylaxis and therapy of neonatal isoerythrolysis in foals are presented. Neonatal isoerythrolysis is caused by isoimmunisation of a brood mare to the Aa and Qa erythrocyte antigens of the foal. The disease can develop, when the mare does not possess Aa resp. Qa blood group antigens, is sensitized to the Aa or Qa erythrocyte antigens--i.e. through pregnancy, parturition, blood resp. plasma transfusions, etc.--and the foal suckles colostral antibodies to its own blood cells. Aa and Qa antibodies can cause haemagglutination and haemolysis in the foal, with a consequent decline in erythrocytes, PCV and haemoglobin resulting in several clinical symptoms. In most instances the first signs of the disease are noticed by day 2 and 3, ranging from 8 to 96 hours of life. Diagnosis is based upon clinical examination and determination of erythrocyte count, PCV and haemoglobin concentration and can be further confirmed by immunological tests. Several tests can be used to prevent the occurrence of neonatal isoerythrolysis in the newborn foal. Prior to parturition, brood mares can be typed for blood groups and tested for antibodies to Aa and Qa in order to identify mares at risk for causing neonatal isoerythrolysis in the foal. After birth, compatibility of the mare's colostrum and the foal's erythrocytes can be checked by the "jaundice foal agglutination" test. Some instructions for prophylaxis of neonatal isoerythrolysis and for the treatment by red blood cell resp. whole blood transfusions are given. PMID- 1759269 TI - [Bilateral ectopic ureter in a Persian cat--a possible cause of urinary incontinence]. AB - A bilateral congenital dislocation of the ureter in a one year old male Persian cat is discussed. Diagnostic procedures, operative implantation of both ureters into the bladder, postoperative course and therapy are described. PMID- 1759270 TI - [Cystocentesis in dogs and cats]. AB - The technique of cystocentesis in dogs and cats was studied. The indications and contraindications of this method are discussed, using illustrations. PMID- 1759271 TI - [The diagnosis of nephrogenic diabetes insipidus in the dog]. AB - Nephrogenic diabetes insipidus is characterized by polyuria, hyposthenuria and compensatory polydipsia. With conventional clinical and laboratory examinations the diagnosis can be established and the differential diagnostic diseases excluded. In order to verify the diagnosis, differentiate the condition from central and nephrogenic diabetes insipidus and rule out psychogenic polydipsia, additional laboratory studies are required: of these, the concentration test, modified Carter-Robbins test and AVP stimulation test are described. PMID- 1759272 TI - [Experiences with a sedimentation technique for the enrichment of cerebrospinal fluid cells in the dog and cat. Part 1]. AB - The differentiation of cells of the cerebrospinal fluid (CSF) gives valuable information about certain neurologic diseases. The sedimentation technique of Sayk modified by Kolmel is introduced and its application described. Cells of 300 samples of CSF from dogs and cats are evaluated. There were very good to reasonable results in 88% (263 of 300) of the samples. A comparison between cell number, morphology and protein content in 150 samples was performed. 90 CSF samples with normal cell count (less than or equal to 5/mm3, determined in the Fuchs-Rosenthal chamber) were compared with the cell yield after sedimentation. In 58% (52 of 90) of the samples more than 200 cells were found, in 13% (12 of 90) more than 800 could be differentiated. The results are compared with those of other methods mentioned in the literature. PMID- 1759273 TI - [Modification of the global coagulation tests for the dog. Significance for the monitoring of heparin therapy]. AB - When the global coagulation tests Quick's test, aPTT and thrombin time are carried out on dogs using reagents from the human medical sector according to the manufacturer's instructions, they react insensitively to deficiencies of the corresponding coagulation factors or to the presence of fibrin degradation products. In the present study it was attempted to develop sensitive global tests for the dog by modifying these tests. The Quick's test reacted apparently more sensitively after a 1:4 dilution of the test plasma with physiological saline solution. The sensitivity of the aPTT was demonstrated by the addition of BaSO4 adsorbed plasma to normal plasma. It seems to be particularly advantageous to combine a 1:3 plasma dilution with a reduction in the CaCl2-concentration to 5 mmol/l. Likewise, plasma dilution allows the thrombin time to react more sensitively in the presence of increased concentrations of fibrin degradation products. The aPTT and thrombin time are, as in human beings, suited for the control of a heparin therapy. However, since prolongation of the coagulation times is considerably dependent on the test chosen, the heparin sensitivity of the test should be determined in vitro prior to use. PMID- 1759274 TI - Family planning operations research in Africa: reviewing a decade of experience. AB - Between 1979 and 1990, Columbia University conducted 26 family planning operations research (OR) projects in 13 sub-Saharan African countries. Most of these projects were implemented in settings where family planning service delivery had not yet been initiated or was new and poorly developed. In keeping with program needs in the early stages of development, the majority of the OR projects were based on demonstration or diagnostic designs. Only four of the 23 projects were comparative or quasi-experimental in design. Projects demonstrated the growing demand for family planning, and the feasibility and acceptability of a range of service delivery models. Sixteen of the projects have been sustained or replicated by national or local governments and institutions following the initial OR phase, replication of two others is planned, and another four resulted in policy formulation or improvements in existing national programs. OR in Africa played an important role in generating political and medical support for contraceptive services, and served to improve project management. OR proved more useful in the implementation and strengthening of individual programs than in generating universal lessons regarding service delivery. In order to maximize OR's utility in Africa, simple research designs and methods should be adopted. PMID- 1759275 TI - Rethinking postpartum family planning. AB - This article examines the rationales for commonly advocated postpartum family planning services and challenges the behavioral and biological assumptions on which they are based. An alternative approach to service delivery is suggested. Services should be designed to incorporate breastfeeding and to increase their acceptability to postpartum women. PMID- 1759276 TI - Fertility and family planning in Vietnam. AB - This report provides the first reliable statistical data on fertility patterns and the family planning program in the Socialist Republic of Vietnam. Findings are from the 1988 Demographic and Health Survey of Vietnam and the 1989 census survey. The data show that the total fertility rate has declined from over 6 children per woman in the early 1970s to under 4 in the later 1980s. Contraceptive prevalence for modern methods is estimated at 37 percent among married women of reproductive age in 1988. The average duration of breastfeeding is over 14 months; marriage is relatively late. The IUD is the most common contraceptive method and abortion is widespread. The major factors likely to influence fertility and family planning in the future are the government's population policy, improved access to modern methods of contraception, and the institution of new economic policies that are currently under way in Vietnam. PMID- 1759277 TI - Perceptions and practices relating to condom use among urban men in Haiti. AB - This report is based on a survey conducted in 1986-87 of sexually active adult male residents in a low-income community of Port-au-Prince, Haiti. The objectives were to investigate knowledge of and attitudes toward condoms; to evaluate the effectiveness of the existing condom distribution program; and to obtain information that can be used in the design of strategies to increase condom acceptance and use among men throughout Haiti. A final sample of 706 sexually active adult male residents in stable unions, including a specially drawn sample of male partners of condom acceptors, were interviewed in their homes. Although condoms are almost universally known, they are rarely used. The majority felt that the responsibility for family planning should be borne by the woman. Whereas condoms may be of limited popularity for family planning purposes in Haiti, it should be determined whether they might be more acceptable as an effective means of controlling the spread of AIDS and other STDs. PMID- 1759278 TI - Family planning information sources and media exposure among Zimbabwean men. AB - This report describes, for a sample of Zimbabwean men, sources of family planning information, media exposure, media preferences, and whether they would like to learn more about family planning methods. The data are from the 1988 Zimbabwe Male Fertility Survey, a representative sample of 711 currently married men aged 20 and over. The analysis is restricted to the 512 men whose wives were aged 49 and under at the time of the survey. The radio and personal communications, followed by posters and newspapers, are the most frequently reported sources of family planning information. The radio is considered to be the best medium for learning about family planning, followed by community-based distributors. Nearly 85 percent of respondents indicated that they would like to learn more about family planning. Information from men should be included in information, education, and communication programs in order to enhance male involvement in the family planning process. PMID- 1759279 TI - What's wrong with CYP? PMID- 1759280 TI - Kenya 1989: results from the Demographic and Health Survey. PMID- 1759281 TI - [The forensic medical diagnosis of the types of vehicle-caused trauma by using mathematical methods and programming systems]. AB - Urgent problems of scientific research on medicolegal evaluation of vehicle trauma were studied. One of perspective ways of increasing scientific control and evidential value of expert conclusion is pointed out. Use of mathematical methods and personal computers in expert evaluation of vehicle trauma is recommended. Expert differential diagnostic system (impact-overrun) developed is described and operating condition of personal computer is given. PMID- 1759282 TI - [The forensic medical aspects of the biomechanics of the impact interaction of a blunt solid object and the human head]. AB - Issues of distribution of kinetic energy of traumatizing object in direct contact interaction with head during impact are discussed from position of biomechanics. It was stated that kinetic energy is directed at deformation of head tissues and object as well as at head displacement after impact and overcoming neck tissue resistance. Experimental studies confirmed theoretical principles. Results obtained can be used in expert practice and in scientific research. PMID- 1759283 TI - [Mechanical damages to the hair in head trauma from blunt metal objects]. PMID- 1759284 TI - [The selective spatial filtration of roentgenograms in the forensic medical expertise of stab-cutting wounds]. AB - Investigation of 14 roentgenograms of skin preparations with cut-stab wounds, treated by spatial filtration method in medium and high spatial frequency modes was performed using material of 13 specific cases. This resulted in detection of disturbances of skin pattern left at the area of former skin cone in 7 cases while in 2 cases indistinct heel traces were seen. Changes in skin pattern were not recorded on roentgenograms of skin preparation of 12 experimental cut-stab wounds obtained on cadaveric skin. PMID- 1759285 TI - [The expertise of strain disease]. AB - Overload disease (OD) of human osseous system appears after microtrauma and excessive and frequently repeated load. Examination of 260 patients with OD was carried out. Radioisotope method revealed disease in all cases while radiological method--in 91% of cases. Sudden decrease in growth hormone (HGH) was noted in 95% of cases. Classification of 5 stages of OD which can be used for expert practical work was developed. PMID- 1759286 TI - [The restrictase analysis of human DNA as a method for determining genetic sex in forensic biological expertise]. AB - In this article phenomena related to sex heteromorphism of restrictase hydrolysates of DNA, isolated from objects of expert analysis was recommended for use. The performed investigations allow one to work out the system of discriminating sex of biological objects, based on restrictase analysis of human DNA and on registration of sex-specific restrictase fragments. Possibilities of method and its value for gene-identification expertise were illustrated using certain cases from expert practice. PMID- 1759287 TI - [The establishment of the presence of sperm in stains by an agar gel electrophoretic method]. AB - Comparative investigation of seminal stains and other secretions from human body and blood as well as objects of plant origin by gel electrophoresis using alkaline values of pH buffer solutions and subsequent enzymography for acid phosphatase made it possible to develop optimal conditions for detection of seminal presence in stains. Good preservation of seminal acid phosphatase in stains during several years is shown. PMID- 1759288 TI - [The use of personal computers for the mathematical processing of the results of chemical-toxicological studies]. AB - Three programs in BASIC and SUPER BASIC language for personal computer are suggested. The first program makes it possible to calculate the degree of substance extraction and factor of its distribution between two liquid immiscible phases. The second program is designed to make calculations on distribution of substance in the organs of experimental animals. The third program is designed to determine specific and molar factors of light absorption. Results of calculations are presented as tables. Programs can be also used in mathematical processing of results obtained in the course of scientific research. PMID- 1759289 TI - [The forensic medical expertise of carbon monoxide poisonings in the cases of the explosion of methane and coal dust in a mine]. PMID- 1759290 TI - [The pathogenesis and pathomorphology of diffuse cerebral reactions in closed craniocerebral trauma]. PMID- 1759291 TI - [The significance of physiologically active substances in the forensic medical determination of the chronobiological characteristics of injuries]. PMID- 1759292 TI - [The methodological aspects of establishing the time of death]. AB - Methodological analysis of essence of problem concerning postmortem interval estimation is given. The authors present the most promising ways of scientific research on this problem and possibilities of practical use of results of scientific research. The general methods of postmortem interval estimation including wired-in analogy (criterial) method and methods of modelling postmortal processes (mathematical and physical) are analysed. Graph of logical structures of modes of postmortem interval estimation and means of their realization is given. PMID- 1759293 TI - [The dynamics of oligophrenia from the forensic psychiatric aspect]. AB - Clinical-catamnestic examination of patients with oligophrenia (71 subjects) who performed socially dangerous acts and were brought to the Research Institute of General and Forensic Psychiatry named after V. P. Serbskii for in-patient forensic psychiatric expertise was carried out. All the individuals examined are people who at least once were recognized irresponsible with diagnosis "oligophrenia at debility level". Presence of dynamic shifts both in main symptomatology of illness and in concomitant emotional-volitional manifestations were detected; prognostic variants of disease development and social adaptation of oligophrenics were noted. Group of patients with mental deficiency, who needs introduction of "limited sanity" term was singled out. PMID- 1759294 TI - [The forensic medical aspects of using safety belts]. PMID- 1759295 TI - [The postmortem diagnosis of fatty hepatosis in pregnant women]. PMID- 1759296 TI - The assessment of suicidal behavior in adolescents. AB - All available assessment instruments (N = 29) used to study suicidal behaviors in adolescents and young adults (age 12-20) were collected and reviewed. Instruments were found to vary substantially in purpose, format, informat, and theoretical orientation. The items from these tools (N = 461) were categorized according to behavior type (thoughts, feelings, or actions) and content categories (death/life related, disease-promoting/preventing, injury-producing/reducing, person reducing/enhancing, and factual information). The majority of the items were found to assess thoughts and were focused on death-related content. Recommendations include the need for more rigorous validation of instruments, clearer operational definitions, additional normative information, and expansion of the pool of available items to encompass a broader array of self-destructive behaviors. PMID- 1759297 TI - Clinical psychology graduate education in the study of suicide: availability, resources, and importance. AB - Psychologists run the risk of losing a patient to suicide and of experiencing the traumatic impact of this event. The present study examines current levels of training in the study of suicide in the member-departments of the National Council of Schools of Professional Psychology (NCSPP--N = 33), comparing these findings with the level of training in member-departments (N = 115) of the Council of University Directors of Clinical Psychology programs (CUDCP). Eighty percent of the CUDCP departments (N = 92) responded, and of these, only 35% offer formal training in the study of suicide; whereas in the 76% of the NCSPP programs that responded, 56% offer formal training. Although the NCSPP programs seem attitudinally more receptive and supportive of formal training (graduate and postgraduate) in the study of suicide, the NCSPP programs do not significantly differ from their CUDCP counterparts in the actual availability of such formal training. Even when all training efforts of the CUDCP and NCSPP programs are combined, only 40% of all graduate programs in clinical psychology offer formal training in the study of suicide. PMID- 1759298 TI - Teen suicide and changing cause-of-death certification, 1953-1987. AB - This study examines whether the purported tripling in teenage suicides since the 1950s represents a real increase or is simply an artifact of the increased skill of medical examiners in distinguishing youth suicides from fatal accidents. This study examines firearms and poisoning deaths, which together account for 75% of all certified youth suicides, from 1953 through 1987, and concludes: (a) a past undercount of youth suicides is likely, (b) the increase in youth suicide that has occurred is less dramatic than reported and resembles increases in adult suicide, and (c) the suicide increase indicated among youths and adults occurred from 1964 to 1971 and has since stabilized. PMID- 1759299 TI - Suicidal behavior in Italy: data, trends and guidelines for a suicide intervention/prevention policy. AB - Even though in Italy, as in the majority of Mediterranean countries, the increase in suicide rates is not among the highest in Europe, between 1969 and 1989 it showed a sharp upswing (+43% among males and +31% among females). In terms of geographical differences, the regions with the highest suicide rate are the northern ones (up to twice the national average). The age groups with the highest suicide risk are those over 74 years (in 1989 the rate among males over 65 was the highest of all: 31.3 per 100,000). The differences in the between-sexes distribution show that among females over 65 years old the suicide rate rose by 70% between 1974 and 1989, versus 77% for males of the same age. The preliminary epidemiological results of one of two Italian centers are presented. These centers are collaborating with the WHO/EURO Multicenter Study on Parasuicide; parasuicide rates are higher for females than for males (55.9 per 100,000, as against 38.1 for males), while the age group at highest risk is seen to be young women (15-24 years), with a specific rate of 115.6. PMID- 1759300 TI - Suicides in active-duty enlisted Navy personnel. AB - Cases of completed suicide among U.S. Navy enlisted personnel occurring from 1974 through 1985 were identified and compared with similar rates in the U.S. general population and in the U.S. Army. Although the Navy suicide rate was the lowest of the three groups, this rate increased between 1976 and 1983. This was in contrast to national and Army trends during the same period. Young white males in the apprentice/recruit and blue-collar occupations had the highest rates of completed suicide in the Navy. Recommendations for prevention and treatment are discussed. PMID- 1759301 TI - Suicide prevention in the Pacific War (WW II). AB - During the war against Japan, there were two facets of an American program to prevent suicide among the Japanese. One was a research component in the Foreign Morale Analysis Division (FMAD), a subunit of the Office of War Information. The principal FMAD figure who did most of the research on Japanese suicide and ways to prevent suicide among the Japanese military was the anthropologist Ruth Benedict, assisted by her Japanese-American aide Robert Hashima. The second facet was the suicide prevention program itself, which was put into effect toward the end of the war in the battles of Saipan and Okinawa. This program of action was undertaken by American GIs. These unheralded activities in suicide prevention merit a place in the annals of suicide prevention programs. PMID- 1759302 TI - Case consultation. David. PMID- 1759303 TI - [The Zollinger-Ellison syndrome]. PMID- 1759304 TI - [Therapeutic aspects of traumatic perforations of the colon. 22 cases]. PMID- 1759305 TI - [Cancers of the mouth]. PMID- 1759306 TI - [Spontaneous evolution of ventricular septal defects after the age of 2 years]. PMID- 1759307 TI - [Left intra-auricular myxoma. 13 cases]. PMID- 1759308 TI - [Bronchial foreign bodies in the adult. 4 cases]. PMID- 1759309 TI - [Hormonal parameters and fluid-electrolyte imbalances in primary hypothyroidism]. PMID- 1759310 TI - [Hypocalcemic cardiac insufficiency in the adult. 2 cases]. PMID- 1759311 TI - [Suppuration of a ovarian dermoid cyst. Case report and review of the literature]. PMID- 1759312 TI - [Franceschetti-Klein mandibulofacial dysostosis. A case report]. PMID- 1759313 TI - [Exercise-induced asthma]. PMID- 1759314 TI - ["Sunday athletes" and lipid evaluation]. PMID- 1759315 TI - [Biliary enteric fistulas. Report of 11 cases]. PMID- 1759316 TI - [Infection profile of hospitalized diabetics: study of 135 cases]. PMID- 1759317 TI - [Gastritis and campylobacter pylori. 85 cases]. PMID- 1759318 TI - [Cervico-facial cellulitis. 20 cases]. PMID- 1759319 TI - [Diagnosis and effects of subclinical varicocele on fertility. 6 cases]. PMID- 1759320 TI - [Primary Budd-Chiari syndrome. Review of the literature and 5 case re ports]. PMID- 1759321 TI - [Drugs and embryonic-fetal development]. PMID- 1759322 TI - [Multiple myeloma manifesting as recurrent phlebitis]. PMID- 1759323 TI - Description of broad-band pulsed Doppler ultrasound processing using the two dimensional Fourier transform. AB - Considering data from a Doppler sample volume as a two-dimensional function of depth and time, the properties of its two-dimensional fast Fourier transform (2DFFT) are discussed. It is shown that the 2DFFT of idealized Doppler data from moving scatterers is a line whose slope is the velocity of the scatterers. Aliasing, finite bandwidth effects, and spectral broadening due to transit time effects receive simple descriptions in this scheme. Existing processing schemes can be described graphically in this unifying description. Processing of broad band pulsed Doppler ultrasound can incorporate a correction for aliasing if based on the two-dimensional Fourier transform, and this has been tested using data from tissue-mimicking phantom in a tank-based experiment. PMID- 1759324 TI - A simulation study of echographic imaging of diffuse and structurally scattering media. AB - Realistic simulations of echographic image formation were performed. The simulations were based on a focussed single element transducer of 3.5 MHz and linear scanning. The tissue model scanned was composed of a homogeneous, nonattenuating, medium containing point-like scatterers. The scatterers were distributed in space in two different arrangements: randomly with a fixed number density of 7500 per cubic centimeter and regularly in a cubic matrix with a characteristic distance of 1 mm. These two populations of scatterers yielded the diffuse and the structural scattering component, respectively. The B-mode texture was assessed by first and second order statistical parameters. The effects of various modifications of the matrix, i.e., the relative scattering strength, the orientation and the position uncertainty of the scatterers, on the statistical parameters were systematically investigated. Increasing the relative scattering strength yields a monotonic increase of the mean grey level, the ratio of structural over diffuse scattering intensity and a decrease of the signal-to noise ratio and the autocorrelation lengths. Increasing the position uncertainty to 20 percent reduces these effects practically to zero, except for the lateral ACF's. Rotation of the matrix with respect to the beam axis induces a periodicity in all statistical parameters, which is symmetric around 45 degrees. Again, the effects become statistically insignificant at a position uncertainty of 20 percent, with the exception of length of the lateral ACF. While assuming that in a single clinical B-mode echogram of the liver many orientations of the matrix will be simultaneously present, the B-mode lines of images obtained for a range of orientations were taken together and the overall statistical parameters calculated. The mean, the signal-to-noise ratio of the echo amplitude, SNRA, and the axial and lateral lengths of the ACF for the multirotation condition are significantly different from both the diffuse and the zero degree orientation. The structural backscattering intensity cannot be estimated any more with a reasonable precision. The structural separation distance, however, can still be assessed at a 10 percent level of the position uncertainty, even in the multirotation case and is therefore a robust clinical parameter. PMID- 1759325 TI - An iterative algorithm for scanning tomographic acoustic microscopy. AB - Acoustic microscopy is capable of providing high-resolution images of small objects. When such a microscope operates in the transmission mode, it produces simply a shadow-graph of all the structures encountered by the acoustic wave passing through the object. The resultant images are difficult to comprehend because of diffraction and overlapping of complex structures. Scanning tomographic acoustic microscopy (STAM) overcomes these difficulties and produces unambiguous micrographs of objects of substantial thickness and complexity. STAM uses the back-and-forth propagation algorithm to reconstruct tomograms of various layers to be imaged. When these layers are physically close to one another, ambiguities appear in the reconstructed images. Using an iterative algorithm eliminates these ambiguities and resolves layers that are only two wavelengths apart. PMID- 1759326 TI - Improved resolution backscatter coefficient imaging. AB - This paper reports the extension of a method for imaging acoustic backscatter coefficients that allows for greater spatial resolution in the resulting images. This is done by using a broad-band excitation pulse and short-duration time gates in the analysis. The images produced had better spatial resolution than the previously reported technique [Ultrasonic Imaging 10, 121-138]. Furthermore, the pixel values were based upon quantitatively accurate backscatter coefficients at given spatial locations. The paper also discusses the additional computational requirements of greater spatial resolution and proposes a least-squares fit to a smoothly varying set of sparse data to generate the data points in between. PMID- 1759327 TI - The problem of obstruction in prostate cancer. PMID- 1759328 TI - Photodynamic therapy of bladder cancer--uptake and phototoxicity of photosan in vitro. AB - The uptake of photosan and the intracellular sites of photoradiation-induced damage were investigated in vitro in bladder carcinoma cells and in normal bladder cells. Cells were examined by phase contrast, fluorescence and electron microscopy. The concentration of photosan, measured in microgram/10(6) cells, showed a good correlation to the incubation time. At all incubation times, control cells showed a lower uptake when compared with tumor cells. Following photodynamic therapy (PDT), phase-contrast microscopy revealed marked changes in tumor cells, whereas only minor effects could be detected at the cell membrane of the control cells. Following PDT, most of the investigated cells showed changes of the mitochondria and cytoplasma. These changes consisted of dissolution of the cristae, predominantly in the central part of the mitochondria. Twenty-four hours after PDT the shape of the mitochondria had changed markedly and the cristae were found to be completely destroyed. Moreover, the cystoplasma showed numerous vacuoles, and the number of mitochondria was decreased compared to non-treated cells. PMID- 1759329 TI - Determination of DNA ploidy and ABH antigen reactivity in both frozen and formalin-fixed bladder tumor tissue. AB - In a prospective series of patients with transitional-cell bladder carcinomas, DNA ploidy and ABH antigen reactivity were determined in both frozen tissue and formalin-fixed paraffin blocks. ABH antigen measurement in frozen tissue was hampered by methodological problems, especially insufficient morphology, which made quantification difficult. In only 38/55 (69%) cases was the same ABH reactivity found. The knowledge of secretor status was not helpful in the interpretation of these results. In 53/59 (90%) cases the same DNA ploidy was achieved, resulting in good correlation between flow cytometric DNA measurements in formalin-fixed and frozen tissue. The deviations occurred mainly in cases exhibiting a tetraploid DNA profile. DNA assessments using image cytometry on imprints of fresh tissue was a rapid and reliable method in our hands, with identical results being obtained in 32/36 (89%) cases. PMID- 1759330 TI - Alterations in polymeric immunoglobulin receptor expression and secretory component levels in bladder carcinoma. AB - To assess the capacity of transitional cells to synthesize the release polymeric immunoglobulin receptor (pIg-R) in bladder carcinoma, we studied the localization of pIg-R in normal and tumor tissues and measured the levels of secretory component (SC) either in the free form or bound to Ig (S-IgA, S-IgM) in the serum and urine of 56 patients with transitional-cell carcinoma (TCC) of the bladder. In the normal bladder mucosa, pIg-R was localized in the cytoplasm and plasma membranes of the superficial cells and on all epithelial cell membranes. In TCC cases, 65% of those studied expressed pIg-R. A marked heterogeneity in pIg-R staining was observed in some tumors. Although a better expression of pIg-R in tumors with a well-preserved epithelial architecture was observed, no correlation was found between pIg-R expression and the grade or stage of the tumors in the patients under study. Three groups were established: (1) in TCC with no complications, serum levels of free SC and S-IgA were significantly increased; (2) in TCC with urinary infections (UI), serum levels of free SC and S-IgA were significantly higher than control values but lay within the same range observed in TCC with no complications and rates of urinary excretion of SC were significantly higher than those in normal subjects; (3) in TCC without UI but with hepatic disorders [high gamma-glutamyl transferase (GGT) activity], there was a correlation between serum S-IgA levels and GGT activity (r = 0.5, P less than 0.005) and serum SC levels were significantly higher than those observed in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759331 TI - Tumor necrosis factor in benign and malign tissue of the kidney. AB - The use of tumor necrosis factor (TNF) in immunotherapy of tumor diseases has attracted increasing interest. Since the direct antitumor effect of the TNF is mediated by receptor-bound TNF, we immunohistologically stained both benign and malignant tissue from 35 tumor-bearing human kidneys for TNF. Using a polyclonal anti-TNF-antiserum, paraffin sections were tested in the presence and absence of in vitro preincubation with TNF. Furthermore, all specimens were stained immunohistologically for Tamm-Horsfall protein (THP) because this renospecific glycoprotein can bind TNF in a lectin-like manner. In the absence of TNF preincubation, malignant tissue was TNF-positive in 34 specimens, as was benign tissue from the same tumor-bearing kidneys in 35 cases. In several specimens the staining was so intense that preincubation with TNF did not enhance the reaction. Whereas TNF staining in tumor tissue was relatively homogenous, that in benign tissue was intensive in distal tubuli, moderate in proximal tubuli, and negative in glomeruli. THP staining was negative in malignant kidney tissue but positive in the distal tubuli of benign tissue, i.e., in the regions in which TNF staining was most intense. These results indicate that TNF binds not only to membrane, most likely in a receptor-mediated manner, but also to THP both in vivo and in vitro. In vivo binding of TNF to THP was confirmed in animal experiments in which pigs were given injections of TNF. Immunohistological staining of the animals' kidneys revealed positive reactions for both TNF and THP at the distal tubuli, indicating TNF binding to THP after in vivo TNF administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759332 TI - Glycosaminoglycans, uric acid and calcium oxalate urolithiasis. AB - The interaction between calcium and glycosaminoglycans (GAGs) was studied using a calcium ion-selective electrode. The Ca-binding capacity of GAGs involved 16% of total calcium in the presence of chondroitin sulphate and 28% in the presence of pentosan polysulphate. The action of GAGs on the nucleation of uric acid and sodium urate was examined and inhibitory effects were observed. The action of uric acid as a heterogeneous nucleant of calcium oxalate was studied, and considerable promotion of the heterogeneous nucleation of calcium oxalate by uric acid was found, which could be inhibited by the action of GAGs. From these summarised in vitro results, we conclude that uric can constitute an important risk factor for calcium oxalate urolithiasis through heterogeneous nucleation and the GAGs can play an important role as preventive agents. PMID- 1759333 TI - Rate of urinary bladder blood flow evaluated by 133Xe washout and radioactive microspheres in pigs. AB - Urinary bladder blood flow as measured by the washout of locally injected 133Xe and by the simultaneously performed radioactive microsphere reference-sample method was studied in pigs. The washout curves were analyzed according to the initial slope, the corrected initial slope and the total curve. The corrected initial-slope flow rates were not statistically significantly different from the microsphere whole-wall flow rates. The variability between the methods shown by the test-retest difference revealed only a minor lack of agreement. The bladder blood flow tended to decrease after the intravesical pressure had been increased to 20 cmH2O, but the difference was not statistically significant. Washout of locally injected 133Xe can be used for the evaluation of urinary bladder blood flow in humans and in longitudinal animal studies. The corrected-initial-slope method is recommended for the analysis of washout curves. PMID- 1759334 TI - The role of oxygen free radicals and prostaglandins in reperfusion injury to warm ischemic kidneys. AB - The present study was designed to determine whether the administration of superoxide dismutase (SOD) can alleviate ischemic kidney damage and whether there is a relationship between oxygen free radicals and thromboxane (Tx). In 17 dogs, the right kidney was removed and the vascular pedicle of the left kidney was clamped for 75 min. Prior to reperfusion, the ischemic kidney was rinsed with 5 mg SOD and an additional 20 mg SOD was infused systemically. Blood samples were drawn from the renal vein before ischemia and after reperfusion to determine serum levels of thromboxane B2 (TxB2). All eight untreated dogs died within 1 week of renal failure, and the nine treated dogs demonstrated transient renal failure, with a significant difference (P less than 0.001) being found between the two groups. A significant difference (P less than 0.001) in TxB2 levels was found in the untreated dogs before and after ischemia and between the two groups following reperfusion. Animals that are treated with SOD after the ischemic event has occurred but before reperfusion exhibit a favorable clinical course in terms of survival and renal function. Tx synthesis in the kidney can be blocked by the administration of SOD. PMID- 1759336 TI - International disease surveillance. Quarterly report June to September 1991. PMID- 1759335 TI - Effects of direct current on renal function. An experimental study in pigs. AB - Electric current from an external source was introduced between electrodes operatively placed into the ureters and positioned in the renal pelves of 13 pigs. Urinary excretion via the cathodic kidney showed a marked increase. The renal plasma flow and glomerular filtration rate diminished with increasing voltage, but no significant difference was found between the cathodic and the anodic kidney. The fractional sodium excretion by the cathodic kidney was 80% higher, indicating that the electric current mainly affected tubular function. A possible clinical application for electric fields in the kidneys is discussed. PMID- 1759337 TI - Control of fly strike in sheep by means of a pour-on formulation of cyromazine. AB - Cyromazine, a triazine insecticide, was used as a pour-on preparation to prevent blowfly myiasis in sheep kept in pairs of neighbouring farms in two locations. In 1987 one of the farms in each location used conventional dipping with a diazinon dip while the other used the pour-on treatment. The results achieved with the pour-on preparation compared favourably with the results of conventional dipping and the incidence of blowfly strike was substantially lower than the proportion affected among the untreated groups on the same farms. The 1988 trial results confirmed the efficacy of the pour-on treatment for up to 13 weeks and that retreatments at eight-weekly intervals could reduce the incidence of fly strike to zero. PMID- 1759338 TI - Value of standardised exercise tests and blood biochemistry in the selection and training of breeding stallions. AB - Stallions selected by the Royal Dutch Warmblood Society were submitted to a standardised lungeing test at the beginning and at the end of a 100-day test of performance and ability. The heart rate, haematology and biochemistry values obtained in the first lungeing test showed no significant differences between the 15 stallions which were rejected by the Royal Dutch Warmblood Society during the first month of the 100-day test, the 15 stallions rejected during the last month and the 11 stallions which were approved for registration in the studbook. The 26 stallions submitted to the second lungeing test had significantly lower heart rates and blood lactate concentrations than in the first test. The standardised lungeing test had no value in predicting the rejection or approval of the stallions, and the fitness of a stallion at the beginning of the 100-day test did not influence its chance of being approved as a breeding stallion. The differences between the results of the first and the second tests suggest that the fitness of the stallions improved during the 100-day test. PMID- 1759339 TI - Failure of sheep to respond to repeated inoculations with an alcelaphine herpesvirus-1-like virus, isolated from a case of malignant catarrhal fever in American cattle. AB - The replication of an alcelaphine herpesvirus-1-like virus (707K), isolated from a clinical case of malignant catarrhal fever in American cattle, was studied in sheep. Viraemia was not observed in any of the six sheep repeatedly inoculated with the 707K virus or in four steers susceptible to malignant catarrhal fever which were housed together with these sheep for one year. None of the four steers seroconverted and only two of the six inoculated sheep showed a negligible and short-lived seroconversion. The inability of the sheep to seroconvert adequately after repeated inoculations with the 707K virus, and the failure to recover the agent from them suggests that this agent does not replicate in sheep. PMID- 1759340 TI - Attempt to vaccinate orally harbour seals against phocid distemper. PMID- 1759341 TI - Potential danger of avian paramyxovirus type 3 to ornithological collections. PMID- 1759342 TI - Cutaneous salmonellosis in veterinarians. PMID- 1759343 TI - Policy on farm animal welfare. PMID- 1759344 TI - RCVS rules on firing. PMID- 1759345 TI - Toxocariasis campaign. PMID- 1759346 TI - Porcine reproductive and respiratory syndrome in Quebec. PMID- 1759347 TI - Effect of maedi-visna virus infection on lamb growth. PMID- 1759348 TI - Red meat refresher course. PMID- 1759349 TI - [The organization of therapeutic care in accidents at nuclear power installations]. PMID- 1759350 TI - [The prospects for using radiation study methods in rendering care to the victims in areas of accidents and catastrophes]. PMID- 1759351 TI - [The pathogenesis and early therapy of acute radiation lesions]. PMID- 1759352 TI - [The biochemical and immunological indices in the rehabilitation period of the victims of the accident on the Komsomolets atomic submarine]. AB - Biochemical and immunological indexes of peripheral blood were compiled in military sanatorium "Divnomorskoe" in seamen who have suffered from general supercooling in the result of "Komsomolets" atomic submarine breakdown. The patients had the symptoms of metabolic disturbance, immunodepression, a great concentration of proteins in acute phase and activity of MB-fraction of creatine phosphokinase. Immunodepression after the general supercooling was mainly conditioned by oppression of differentiation, metabolic changes and functional activity of T-lymphocytes. A course of immunocorrective therapy was employed using "thymogen"--synthetic peptide of thymus. In the process of rehabilitation there was a gradual functional recovery, normalization of metabolism and immunological indexes. PMID- 1759353 TI - [Mental disorders in officials of the law-and-order service working in the area of the accident at the Chernobyl Atomic Electric Power Station]. PMID- 1759354 TI - [The etiopathogenesis of poisonings by the components of technical fluids]. AB - The studies of peculiarities of aliphatic alcohol metabolism in etiopathogenesis of acute poisoning with methyl alcohol and ethilenglicol have shown that it was reasonable to apply the inhibitors of alcoholdehydrogenase as a specific antidote in emergency therapy. Inhibitors prevent the formation of toxic products by blocking metabolism of these spirits. PMID- 1759355 TI - [The system of medical evacuation support for the troops at the present stage of development of military medicine]. AB - The authors analyse the former and actual state of evacuation support of troops. Having been finally formed during the Great Patriotic War as the system of casualty staging it proved to be correct. At the same time this system has some deficiencies, namely: the repeated surgical intervention, multistaged character of evacuation, medical care and treatment. In the post-war period the improvement of this system is connected with a radical technical re-equipment of medical service, including modern evacuation facilities, as well as with rational assignment of medical specialists. Actually the assurance of an early (within first 6 hours) specialized medical care is considered to be the main task and the basic principle in the improvement of medical evacuation in troops. PMID- 1759356 TI - [Whole-body rheography in the differential diagnosis of critical states in acute poisonings by organophosphorus compounds]. PMID- 1759357 TI - [The prediction of the toxic effect of chemical substances]. AB - On the basis of general conception of the toxicity mechanism of chemical substances the authors worked out a conceptual and mathematical model of intoxication within a range from subtle effects and up to lethal cases. The tests of this model were made on the basis of carbon oxide action. The model gives the possibility to elaborate practical methods for prognostication and realization of health service measures in case of large-scale chemical catastrophes. PMID- 1759358 TI - [The experimental validation of associated immunization with paired combinations of vaccines]. AB - Experimental researches were conducted on reactogenicity and immunological efficiency of pair associations of 8 commercial drug preparations. The following vaccines were used in various pair combinations: typhoid, plague, smallpox, typhus, tick-borne encephalitis, yellow-fever, cholera, sextaanatoxine. Pair combinations of these drug preparations were proved to be harmless. Their reactogenicity was manifested mainly in more or less pronounced vaccination reaction which may be considered as tolerable. Immunological efficiency practically of all pair combinations of vaccines, which was determined by the frequency and intensity of antibody formation, had the same indexes as the control one. The immunity expression of a large majority of pair combinations of vaccines also was unchanged. The study in vitro of compatibility of pair associations of vaccines proves the low stability of yellow-fever vaccine, which falls down under the influence of plague and cholera vaccines, or sextaanatoxine. On the contrary, smallpox vaccine makes yellow-fever vaccine more active. Plague vaccine is stimulated by smallpox vaccine and is oppressed with combined application of typhoid vaccine and sextaanatoxine. PMID- 1759359 TI - [Radioisotopes devices and the sanitary inspection of their use in units and installations of the Army and Navy]. PMID- 1759360 TI - [A rapid method for predicting physical work capacity]. PMID- 1759361 TI - [A method for determining the need for medical stores]. PMID- 1759362 TI - [The UMU-1 and UMU-2 uniform fabric cases for military medical kits]. PMID- 1759363 TI - [Plastic operations with the tubed pedicle flap in combined defects of the perioral area and lower and middle face]. PMID- 1759364 TI - [Experience with the use of dental implantation in eliminating defects of the dental arches]. PMID- 1759365 TI - [The diagnostic and treatment procedure characteristics in foreign bodies of the gastrointestinal tract]. PMID- 1759367 TI - [A device for determining the mobility of the cervical spine]. PMID- 1759366 TI - [Extrafocal transosseous osteosynthesis of the long tubular bones in multiple and combined trauma]. PMID- 1759368 TI - [A box for instruction on how to puncture the cubital vein]. PMID- 1759369 TI - [A combination device for determining convergence and accommodation separately for each eye]. PMID- 1759370 TI - [The pride of Soviet surgery. On the centenary of the birth of S. S. Iudin]. PMID- 1759371 TI - [The effect of naphthalan on the fast potassium current of pond snail neurons]. PMID- 1759372 TI - [The action of sanatorium-health resort treatment on autonomic endocrine regulation in children with functional changes in cardiac activity]. AB - During sanatorium treatment children with cardiac disturbances developed equilibrium between adrenergic and cholinergic effects on cardiac activity. Vegetative dysfunctions declined. There was a positive trend in glucocorticoid and thyroid conditions. Individual application regimens of mud and galvanic mud therapy have been designed basing on changes in the vegeto-endocrine status. PMID- 1759373 TI - [The effect of medical gymnastics on the external respiratory function of patients with infectious-allergic bronchial asthma under ambulatory treatment]. AB - A new treatment of bacterial asthma involving therapeutic exercise, massage and using a special respiration regulator improving bronchial permeability is proposed. The treatment was conducted in 118 patients aged 22-68 with 1-17-year history of asthma. The set of exercises proposed, especially in application of the regulator, improves external respiration, bronchial permeability, helps to reduce hyperventilation and arterial hypoxemia. PMID- 1759374 TI - [The rehabilitative treatment of polyneuropathies in children]. AB - Two hundred children with hereditary polyneuropathy have been examined. A positive time course of clinical manifestations, the status of peripheral blood circulation and neuromuscular system after the exposure to sinusoidal modulated current and electrical stimulation provides evidence for higher efficacy of this method in comparison with inductothermy and local whirlpools. PMID- 1759375 TI - [A comparative evaluation of the effect of balneopsychotherapy, balneotherapy and psychotherapy on osteoarthrosis patients]. AB - Osteoarthrosis patients underwent balneotherapy or placebo treatment with psychotherapy or without it. The response of the patients favors the addition of psychotherapy to osteoarthrosis treatment (clinical differences made up 8-12%). PMID- 1759376 TI - [Physical factors in the postoperative rehabilitation of patients with congenital deformities of the jaw bones]. PMID- 1759377 TI - [The action of an alternating magnetic field on the antiviral protection of cells]. PMID- 1759378 TI - [The use of sinusoidal modulated currents in treating patients with the neuroreceptor form of impotence]. PMID- 1759379 TI - [The use of preformed physical factors during the preoperative preparation and rehabilitation of rectocele patients]. AB - A technique of using preformed physical factors for the treatment of rectocele patients in pre- and postoperative period has been designed. The technique promoted early activation of 36 postoperative females. They recovered functions of the fundus of the pelvis and normal defecation. PMID- 1759380 TI - [Control over mature therapeutic muds]. PMID- 1759381 TI - [A comparative evaluation of the body uptake of iodine in ionic and molecular forms in vaginal irrigations with iodide-bromide water (experimental research)]. PMID- 1759382 TI - [The automation of the methods for studying the gastrointestinal tract in health resort practice]. PMID- 1759383 TI - [The current aspects of the postgraduate training of physicians in physiotherapy, health resort science and medical rehabilitation]. PMID- 1759384 TI - [The moderation of the physical loads in therapeutic physical exercise]. PMID- 1759385 TI - [Cryotherapy]. PMID- 1759386 TI - [Morphofunctional shifts in the thyroid and liver and a change in the thyroid hormone level in the blood with the internal use of iodine-containing waters]. AB - Assessment of thyroid function and antitoxic protein-synthesizing function of hepatocytes at light microscopic and ultrastructural levels revealed differences in the effects of natural and prepared iodine water under similar iodine-ion concentration (14 mg/l). The varieties seem to result from the presence of ion salt base in the natural water. PMID- 1759387 TI - [Prevention of post-resuscitation metabolic disorders by the antioxidant oxypyridine-6]. AB - Acute mortal hemorrhage in rats induced excessive activation of lipid peroxidation, while accumulated high amounts of lipid hydroperoxides impaired energy metabolism in brain and heart tissues. Preadministered antioxidant hydroxypyridine-6, which increased the lipids antioxidation activity and reduced inhibition of the antioxidative enzymes, limited distinctly the lipid peroxidation rate in brain, heart, lung and liver tissues and contributed to maintaining energy metabolism. The drug diminished 2-fold the early postresuscitation lethality. PMID- 1759388 TI - [Change in lipid peroxidation processes and level of individual gangliosides and phospholipids in the liver of rats with toxic experimental hepatitis]. AB - Content of individual phospholipids, gangliosides and lipid peroxidation were studied in liver tissue homogenates of rats with hepatitis caused by CCl4 or heliotrine. In all the cases studied the rate of lipid peroxidation was distinctly increased, while content of sphingomyelin was decreased and that of phosphatic acid--increased; concentration of some gangliosides was altered. Activation of lipid peroxidation appears to induce the enzymatic systems involved in degradation of phospholipids and gangliosides in liver tissue of rats with toxic hepatitis. PMID- 1759389 TI - [Cytochrome P-450 activity and lipid peroxidation in rat liver and lung microsomes during hypoxia and followed by pressure oxygenation]. AB - Influence of hypoxia (0.029 MPa, I h) followed by hyperoxia (0.2 MPa, I h) on microsomal oxidation and lipoperoxidation was studied in rat liver and lungs. Distinct increase of cytochrome P-450 catalytic activity with amidopyrine and benzo-a-pyrene as substrates of the I type was found after hypoxia, subsequent hyperoxia resulted in significant increase of amidopyrine and benzo-a-pyrene metabolism in liver and lung tissues and of aniline metabolism in liver tissue. Both hypoxia and hyperoxia led to increase in content of diene conjugates and Schiff bases in liver and lungs, while the increase of diene conjugates in liver and both diene conjugates and Schiff bases in lungs were observed under hyperoxic conditions. PMID- 1759390 TI - [The role of monoamine oxidase in the regulation of mitochondrial energy functions]. AB - Incubation of aldehyde dehydrogenase-free mitochondrial preparations with biogenic amines serotonin, tyramine, 2-phenylethylamine and 5-methoxytryptamine resulted in inhibition of enzymes activity of both outer (rotenone-insensitive NADH-cytochrome c reductase) and inner (succinate dehydrogenase, succinate cytochrome c reductase) mitochondrial membranes. Solubilization of mitochondria after the incubation did not influence the amine-induced alteration of succinate dehydrogenase activity. Pretreatment of the organelles with a mixture containing chlorgyline and deprenyl completely inhibited monoamine oxidase (MAO) activity and prevented the effects of all the amines studied on mitochondrial enzymes. MAO dependent effects of 5-methoxytryptamine were fully reproduced by 5 methoxyindolyl-3-acetaldehyde (one of probable products of 5-methoxytryptamine deamination). The effect of the aldehyde was not prevented by chlorgyline and deprenyl. After selective inhibition of MAO-A by chlorgyline the order of MAO-B dependent effects of biogenic amines on mitochondrial enzymes studied was as follows: tyramine greater than or equal to 2-phenylethylamine much greater than serotonin. In deprenyl pretreated mitochondria the potency of MAO-A-dependent effects of these amines was: serotonin greater than tyramine much greater than much greater than 2-phenylethylamine. The data obtained suggest that the product(s) of oxidative deamination of biogenic amines (probably the aldehydes) catalyzed by both types of MAO (MAO-A and MAO-B) are able to regulate the energy functions of mitochondria. PMID- 1759391 TI - [Antigenic properties of lactate dehydrogenase isoenzymes of various biological types using antipeptide antibodies to a fragment of the active center of swine lactate dehydrogenase-M4]. AB - Antigenic properties of human, pig, rabbit and rat lactate dehydrogenase (LDH) M4 isozyme as well as of human LDH-C4 were studied using antipeptide antibodies against pig LDH-M4 fragment (180-214). Amino acid sequence 180-214, containing His-195, which is involved in the active site of LDH isozymes, proved to be total antigenic determinant only for human and pig M4-isozymes. Amino acid sequence of total antigenic determinant did not allow any substitutions of essential amino acid residues. His-195, participating in substrate binding, was not involved immediately in reactions with antibodies as shown by means of chemical modification of pig M4-isozyme with diethyl pyrocarbonate and after production of antibodies against the modified isoenzyme. PMID- 1759392 TI - [Chemical modification of the functional groups of streptokinase B in the water soluble carbodiimide-nucleophile system]. AB - Specific activity of streptokinase was decreased after incubation in the system containing I-ethyl-3(3-dimethyl aminopropyl) carbodiimide (EDC)--ethylene diamine. Under these conditions about 8 free amino groups and 38 free carboxylic groups were modified in the streptokinase molecule. The protein conformation and the state of tryptophane residues were altered. The streptokinase modified by means of EDC-ethylene diamine treatment lost its ability to form a stable complex with human plasminogen. PMID- 1759393 TI - [Irreversible pH-denaturation of tissue thromboplastin]. AB - Irreversible denaturation of tissue thromboplastin from human brain occurred at pH values below 5.0 and above 11.0. Coagulating activity of total phospholipid fraction of thromboplastin was decreased after incubation in acid or alkaline media. PMID- 1759394 TI - [The effect of actinomycin D on lysosomal proteinase activity in murine macrophages and spleen during immune response]. AB - Actinomycin D inhibited activation of lysosomal cathepsins A, B, C, D, H and L in peritoneal macrophages, caused by T-dependent antigen (sheep erythrocytes), of mice CBA X C57BL/6 strain. At the same time, the antibiotic stimulated activity of cathepsins A, C, D and H but decreased content of antibody-producing cells in spleen tissue. Inhibition of lysosomal proteinases in macrophages may be responsible for immunodepressive effect of actinomycin D. PMID- 1759395 TI - [Lysosomal leukocyte glycosidases in childhood bronchial asthma]. AB - Activity of lysosomal glycosidases beta-galactosidase, N-acetyl-beta-D galactosaminidase and N-acetyl-beta-D-glucosaminidase was studied in lymphocytes and neutrophils of children with bronchial asthma. Alterations of the enzymatic activity were found to depend considerably on the disease stage, form, severity, duration and on the sensitization efficiency. Activity of these enzymes was markedly decreased after glucocorticoid treatment while clenbuterol did not affect their activity. The status of leukocyte lysosomal glycosidases appears to be of importance for development of bronchial asthma in children. PMID- 1759396 TI - [Isolation and characteristics of fibronectin from fibrinolytically active human plasma]. AB - Properties of fibronectin, isolated by means of affinity chromatography from blood plasma of suddenly dead persons, were studied. This blood exhibited high fibrinolytic potential and was not capable of clotting due to degradation of fibrinogen. At the same time, fibronectin was also isolated from blood plasma of healthy volunteers. Properties of these fibronectins of dissimilar origin were studied using the following parameters: content of immunoreactive and bioreactive fibronectin in blood plasma, affinity towards gelatin, yield of fibronectin from blood plasma, molecular mass, heterogeneity. Both these fibronectins from different sources of blood plasma were similar in their properties studied, thus demonstrating that any significant degradation of fibronectin did not occur in hyperfibrinolysis in vivo. PMID- 1759397 TI - [Kinetic characteristics of monoamine oxidase in brain regions of animals with varying degrees of sensitivity to 1-methyl, 4-phenyl, 1,2,3,6- tetrahydropyridine]. AB - Kinetic parameters of monoamine oxidase (MAO) were studied in synaptosomal fraction P2 of brain compartments obtained from mice, rats, rabbits, cats, dogs, guinea pigs, macaque rhesus, green and javanese macaques using I-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) as a substrate. Rates of MAO-catalyzed reactions were also studied in animals sensitive to the dopaminergic neurotoxin. At low concentrations of MPTR (about 1-5 mM) the rate of MAO reaction corresponded to the index Vmax/Km. Among the animals studied the highest values of the index were found in guinea pigs and macaque rhesus, the lowest values -- in rabbits. Value of the Vmax/Km index correlated with neurosensitivity to MPTP in neuromelanin-positive and neuromelanin-negative animal groups. The biochemical index for estimation of MAO-catalyzed reactions rates may be used in evaluation of brain compartments neurosensitivity to the dopaminergic neurotoxin and its derivatives. PMID- 1759398 TI - [Use of chloral hydrate for assessing the detoxifying function of the liver in experimental pathology]. AB - A new procedure, developed for evaluation of the liver tissue detoxicating activity in experimental pathology, involved estimation of chloral hydrate pharmacological efficiency and registration of animal sleep duration. As activity of uridine phosphate glucuronyl transferase, the key enzyme of the second step of biotransformation, was found to be inhibited after thermic burns, treatment of the disease using phenobarbital appears to correct the enzymatic activity. PMID- 1759399 TI - [Importance of studying the level of platelet adenine nucleotide levels in various phases of chronic myeloleukoses]. AB - Content of adenine nucleotides was studied in various compartments of blood platelets obtained from donors and patients with chronic myeloleukosis at various steps of the disease. Dissimilar biochemical defect was found in content of ATP and ADP, which varied in thrombocyte storage granules depending on severity of the disease. The data on adenine nucleotides content may be used for diagnosis of various steps of chronic myeloleukosis, for detection of thrombocytes anomaly and for evaluation of the state of medullary hemopoiesis. PMID- 1759400 TI - [Qualitative and quantitative assessment of blood erythrocytes of intact animals under the effect of 5-fluorouracil in solution and in microspheres made of acetylcellulose combined with short-term gas hypoxia]. AB - Resistance of erythrocyte membranes, estimated by means of ultrasound hemolysis, was altered 7 days before the cells quantitative changes after simultaneous treatment of intact animals with 5-fluorouracil, administered as solution or in acetate cellulose drug-containing granules, and short-term gas hypoxia. Simultaneous effect of 5-fluorouracil and hypoxia was less toxic for erythropoiesis, while the long-term form of the drug did not affect considerably the liver tissue functions. PMID- 1759401 TI - [Behavior of ketoamine in animals]. AB - A simple ketoamine 14C-fructosoglycine with all the fructose carbon atoms labelled was synthesized for studies of possible pathways of the ketoamines metabolism in animal body. The ketoamine bond in the fructosoglycine was not hydrolyzed during incubation with homogenates of rabbit liver, kidney, spleen and testicular tissues within 3 hrs at pH 4.8 and 7.3 as well as after hydrolysis with pancreatine (the enzymatic extract from bovine pancreas) at pH 8.4. 14C fructosoglycine administered into rabbit circulation was mainly excreted with urine (about 70% of the label) within 8-14 days. The main part of the ketoamine was excreted as fructosoglycine and the lower amount--as glycated dipeptide; some amount of fructosoglycine was hydrolyzed liberating fructose or converted into aldimine which was hydrolyzed with formation of glucose. The ketoamine was metabolized also into non-reducing isosucrose-like glucofructoside, insensitive to acid and enzymatic hydrolysis. PMID- 1759402 TI - [Anti-radiation activity of alpha- and beta-globulins in blood plasma]. PMID- 1759403 TI - [Effect of thyrotoxicosis on lipid fatty acid composition in various subcellular fractions of the rat brain]. AB - Thyrotoxicosis, which developed after subcutaneous administration of L-thyroxin at a dose of 400 micrograms/100 g of body mass, was accompanied by distinct alteration of fatty acid composition in lipids of adult rat brain myelin, synaptosomes, mitochondria and microsomes. The most significant alterations were detected in synaptosomes and mitochondria. Under conditions of thyrotoxicosis the ratio of polyunsaturated docosahexaenic and docosatetraenic acids was decreased in synaptosome lipids, whereas the content of palmitic, oleic and neuronic acids was increased. The ratio of unsaturated arachidonic and docosahexaenic fatty acids was increased but content of palmitic and linoleic acids was decreased in mitochondrial lipids. PMID- 1759404 TI - [Prospects for correcting the disrupted status of the cardiovascular system in acute myocardial ischemia by combined experimental use of phosphocreatine and corinfar]. AB - Individual and simultaneous influence of phosphocreatine and calcium antagonist corinfar on hemodynamics patterns was studied in experimental acute ischemia of myocardium. Simultaneous treatment with phosphocreatine and corinfar may be effective in ischemic impairment of myocardium. PMID- 1759405 TI - [Role of individual phospholipids in the functional activity of human myocardial creatine kinase]. AB - Regulating effect of individual phospholipids on the activity of creatine kinase MM from human myocardium was studied. Cardiolipin, phosphatidic acid, phosphatidyl serine and phosphatidyl choline (dipalmitoyl) stimulated the enzymatic activity, while phosphatidyl inositol and lysophosphatidyl choline inhibited the creatine kinase MM activity by 80-100%. When mechanisms of the phospholipids inhibitory effects were studied, mixed type of inhibition was detected in the presence of phosphatidyl inositol and non-competitive type--in presence of lysophosphatidyl choline if guanidine was used as a substrate. Phosphatidyl inositol and lysophosphatidyl choline inhibited creatine kinase MM by the uncompetitive type if ADP was used as a substrate. PMID- 1759406 TI - [Disrupted glycerophosphate metabolism in kidney tissue in an inflammatory bronchopulmonary process]. AB - Specific alterations in glycerokinase and glycolytic pathways of glycerophosphate biosynthesis were detected in kidney under conditions of chronic bronchopulmonary inflammation. Considerable inhibition of glycerol kinase and glycerophosphate dehydrogenase resulted in pronounced decrease in content of glycerophosphate- initial metabolite of phosphatide genesis. PMID- 1759407 TI - [The effect of selenium on enzymes metabolizing xenobiotics in rat liver]. AB - Activity of enzymes involved in metabolism of xenobiotics was not altered in liver tissue of rats kept on a ration enriched with selenium at a dose of 2.5 mg/kg. Both organic form of selenium (yeast meal, selenomethionine) and inorganic derivatives (sodium selenite) at a dose of 5 mg/kg of ration caused distinct activation of epoxide hydrolase, UDP-glucuronosyl transferase and glutathione transferase within 6 weeks after the experiment beginning, while content of cytochrome P-450, glutathione-SH and glutathione peroxidase activity were not significantly altered. Within 9 weeks the enzymatic activity remained at the higher rate only in rats kept on the ration with sodium selenite. Relationship between toxic effects of selenium high doses and alterations in activity of enzymes involved in metabolism of xenobiotics is discussed. PMID- 1759408 TI - [Comparison of biochemical criteria for supplying the human body with riboflavin]. AB - Various biochemical procedures were used in evaluation of vitamin B2 occurrence in 38 women. Highly specific procedures for evaluation of riboflavin in blood and urine (high performance liquid chromatography, titration with riboflavin-binding apoprotein, lumiflavin procedure) enabled to detect correlation between values of FAD-effect and excretion of riboflavin with urine as well as of total riboflavin content in erythrocytes, between concentration of free riboflavin in blood plasma and its excretion with urine. All the procedures studied were equally suitable for evaluation of vitamin B2 deficiency as shown by the data obtained as well as by similarity in values of low concentrations which corresponded to normal availability of the vitamin. PMID- 1759409 TI - [Effect of alpha-tocopherol and selenium on the activity of antioxidant enzymes and level of lipid peroxidation products in erythrocytes of patients with cerebral ischemia]. AB - Antioxidant drugs: alpha-tocopherol acetate and "Selenium" (Finland) were used in treatment of patients with small ischemic insult and middle severity ischemic insult; the state of endogenous antioxidant system and intensity of lipid peroxidation were studied in erythrocytes within various periods of diseases. Content of diene conjugates and malonic dialdehyde was decreased, while activity of superoxide dismutase, catalase, glutathione peroxidase and reductase was increased after administration of both these antioxidants during treatment of the brain circulation impairments. Simultaneous use of the drugs caused the highest effect which occurred due to their influence on various pathways of the endogenous antioxidant system. PMID- 1759410 TI - [Effect of a carnitine analog on the level of bile lipids of the enterohepatic system in rabbits in cholelithiasis]. AB - Lipid components were studied in enterohepatic system of rabbits with cholelithiasis after administration of plant components contained in meadow hay as well as of their mixture with a synthetic analogue of carnitine. Hypothetic mechanism of the carnitine derivative effect, contributing to elevation of phosphatidyl choline production in hepatocytes and to accumulation of the phospholipid in bile, is discussed. During the treatment course the calculous form of hepatocholecystitis was not detected in the experimental animals. PMID- 1759411 TI - [Analysis of the reasons for insufficient efficacy of treating inflammatory diseases of the urogenital system in women]. AB - Concentration of tetracycline, doxicyclin and tarivide was studied in blood serum, urine and immediately in the impaired focus, in uterine tube tissue to elucidate the factors responsible for low therapeutic efficiency of drugs involved in treatment of inflammatory diseases of women urogenital system. Content of tetracycline, detected in the patients blood and urine, varied within the limits 0.02-0.12 microgram/ml and 0.003-0.136 microgram/ml, respectively, depending on the period of administration of therapeutic doses of the antibiotic. At the same time, in uterine tube tissue concentration of tetracycline was only slightly increased and constituted 0.014 microgram/ml which was distinctly lower than the minimal inhibitory content for the antibiotic. Similar results were obtained in studies of tarivide concentrations. Both morphofunctional impairments of uterine tubes and deficiency of antibiotics in the impaired focus were responsible for inadequate treatment of women with infertility of inflammatory genesis. PMID- 1759412 TI - [Rapid time-resolved fluoroimmunometric analysis of myoglobin]. AB - High performance quantitative procedure for evaluation of myoglobin in blood serum is developed. The principle of two-site immunometry was used involving monoclonal antibodies against nonoverlapping epitopes of myoglobin molecule. The fluorescent compound containing europium served as a label of the antibody. Modification of the single-step assay enabled to increase the velocity of the assay to about 30 min and simplify it. The assay allowed estimation of myoglobin over a broad range of concentrations from 2 ng up to 1,000 ng/ml. The assay may be recommended for use in clinical practice for express diagnosis of myocardium infarction. PMID- 1759413 TI - [Cholesterol esterification in tissues and change in the apoprotein spectrum in rat blood under the effect of auto-oxidized cholesterol]. AB - Influence of autooxidized cholesterol (Ch) products on accumulation of cholesterol esters (ChE) in liver and aorta tissues as well as alteration of the apolipoprotein spectrum in low density and very low density (LDL and VLDL) lipoproteins in blood plasma was studied in rats treated with purified Ch (ChP rats) and with oxidized Ch containing 5% 25-hydroxyCh and 3% 7-ketoCh (ChO-rats). Increase of ChE content in liver tissue of ChO-rats resulted in two-fold activation of acyl-CoA-cholesterol-O-acyltransferase (ACAT) in liver microsomes as compared with the enzymatic activity rate in ChP-rats. As shown by polyacrylamide gel electrophoresis content of apoE in VLDL and LDL of ChO-rats was 1,5-fold higher as compared with that of ChP-rats. Content of apoIV was increased in LDL and VLDL of ChP-rats as compared with controls; this effect was not observed in ChO-rats. LDL and VLDL from ChO-rats stimulated incorporation of 14C-oleate into ChE of cultivated macrophages. Increase in content of ChE found in aorta of ChO-rats appears to occur due to activation of Ch esterification. Intensification of ChE synthesis in tissues and alterations in the spectrum of LDL and VLDL apolipoproteins caused by oxidized products of cholesterol may be one of the mechanisms involved in atherogenesis. PMID- 1759414 TI - [Diagnostic difficulties in lung mycoses]. PMID- 1759415 TI - [Carcinoid of the appendix]. PMID- 1759416 TI - [An outbreak of legionellosis among the workers of an industrial enterprise]. PMID- 1759417 TI - [The medico-demographic situation in the Ukrainian SSR at the present stage]. PMID- 1759418 TI - [The malignant neoplasm morbidity of the population of the Ukraine in 1976-1989]. PMID- 1759419 TI - [The medical aspects of a systems approach to decreasing morbidity with temporary loss of work capacity]. PMID- 1759420 TI - [The role of expert assessments and pilot observations in social hygiene research on life styles]. PMID- 1759421 TI - [The ethical problems of the rights of unborn children]. PMID- 1759422 TI - [Ukrainian medicine in the mirror of philately]. PMID- 1759423 TI - [Enterosorption: achievements, problems, outlook]. PMID- 1759424 TI - [Functional diseases of the digestive organs]. AB - In this lecture the authors analyze so-called functional disease of the digestive organs, namely disorders of these organs where modern means are unable to reveal organic changes. The role of emotional and psychic factors on functions of the digestive tract and its blood supply is stressed. From 30 to 50% of gastroenterological patients suffer of functional diseases of the digestive organs. Women prevailed (3:1, 2:1). The etiology, diagnosis and treatment of this condition is described in detail. PMID- 1759425 TI - [The methodological characteristics of examining and treating patients with borderline mental disorders]. AB - Discussed are problems of the methodology of diagnosing neuroses, neurosis-like and other borderline mental disorders. The necessity is emphasized of complex and systemic analysis of general somatic, psychological and psychopathological states. An important place is taken by dynamic analysis of the development of pathological states. The importance of these methodology problems for pathogenetic treatment of patients with borderline mental diseases is discussed. PMID- 1759426 TI - [The current concepts of the etiology and pathogenesis of atrial fibrillation]. PMID- 1759427 TI - [The immune mechanisms of recurrent myocardial infarcts]. PMID- 1759428 TI - [The level of vasoactive prostanoids in patients with ischemic heart disease in the early period following aortocoronary bypass]. PMID- 1759429 TI - [An evaluation of the kinin and sympathetic-adrenal systems and prostanoids in rheumatism with a heart rhythm disorder]. AB - A comparative study is presented of some components of the kinin, sympathetic adrenal system and plasma prostacyclin in 296 patients with active rheumatism of different activity grades and disorders of the cardiac rhythm. Data were obtained on the activation of the sympathetic-adrenal and kinin system in rheumocarditis with disorders of the cardiac rhythm. A relationship was established between the components of these systems. The content of prostacyclin in patients with rheumatism in the active phase was reduced. The effect of the mentioned biologically active substances on the development of arrhythmias is discussed. PMID- 1759430 TI - [HLA antigens in patients with different forms of arterial hypertension]. AB - The authors analyze the frequency of HLA [correction of HIA] antigens in 121 male patients with borderline arterial hypertension and in 60 patients with hypertensive disease, stage II. The frequency of HLA [correction of HIA] antigens in these patients was compared with their frequency in the male population of Leningrad inhabitants (858 healthy donors). Patients with borderline arterial hypertension showed a characteristic increase of the frequency of B16, B18 CW4 antigens. The presence of an increase representation of B18 and C4 antigens in both groups makes it possible to consider them as immunogenetic markers of the development of arterial hypertension. PMID- 1759431 TI - [A new approach to assessing the blood biochemical indices in diseases of the internal organs]. AB - The authors propose a new approach to evaluation of biochemical indices in internal organ diseases, namely, comparison of factually detectable results with individual initial data. It was established that in stenocardia the majority of patients showed an increase of activity of cardio-specific enzymes. Patients with exacerbation of obstructive bronchitis revealed diverse changes of the content of immunoglobulins, complement components and proteinase inhibitors. The authors suggest that an individual approach to comparison of laboratory indices reflects more precisely the response of the patient's body to the pathological process. PMID- 1759432 TI - [Xenogeneic splenic perfusion in the treatment of bronchial asthma patients]. AB - Blood morphology, external respiratory function, central hemodynamics, cellular and humoral immunity, circulating immune complexes, average molecules and leucocytic index were examined in 40 patients with a severe and average severe course of infection-dependent bronchial asthma before and after xenosplenoperfusion. Positive clinical results were noted manifested in an increase of the immune reactivity, improvement of external respiratory function. The method should be used with care due to additional sensibilization of the patient and possible bronchospasm. PMID- 1759433 TI - [The correction of disorders in the blood coagulating system during the surgical treatment of patients with pulmonary tuberculosis]. PMID- 1759434 TI - [Changes in the bioenergetic processes and immunoglobulin transport in the stomach tissues of rats after vagotomy]. AB - Data are reported on changes of bioenergetic processes and immunoglobulin transport in gastric tissues after bilateral subdiaphragmatic transsection of the vagal nerves. It was established that the mucosa and muscle membrane of the stomach showed a reduced activity of the glycolysis enzyme. There was also abnormal transport of autogenic immunoglobulins, namely increased penetration of immunoglobulins into the connective-tissue stroma of the mucosa and the surface of epithelium into the gastric cavity. The protein transport into the endomysium of the muscle membrane was sharply reduced. It is concluded that the above mentioned changes reflect development of neurogenic dystrophy after vagotomy. PMID- 1759435 TI - [The beta 2-microglobulin content of the blood serum and urine in patients with primary chronic and lupus glomerulonephritis]. AB - The authors studied the content of beta 2-microglobulin (beta 2-MG) in the blood serum and its excretion with the urine in 85 patients with chronic and 35 with lupoid glomerulonephritis (CGN and LGN) depending on the activity of the disease and state of the renal function. In active CGN and LGN one could observe a distinct increase of the content of beta 2-MG in the blood serum and an increase of its excretion with the urine that may be related to presence of marked dystrophic changes of the canalicular apparatus of the kidneys leading to disorders of reabsorption and beta 2-MG catabolism as well as disorders of the immune homeostasis revealed in these diseases. Results indicate that the beta 2 MG levels in the blood serum and urine may be considered as criteria of CGN and LGN activity. PMID- 1759436 TI - [The dynamics of the psychoemotional state in patients with vibration disease]. AB - Data are presented on the formation of neuropsychic disorders in mine shaft sinkers and drill operators at different stages of vibration disease. Neuropsychic disorders in this category of workers should be considered in the treatment and expertise examination of working capacity. PMID- 1759437 TI - [Infectious-toxic shock in patients with acute pneumonia]. AB - An analysis of case records, medical documentation of the emergency service and out-patient departments of 629 patients with acute pneumonia (AP) showed that infectious-toxic shock was an early grave complication of acute pneumonia. It was observed in 9.4% of patients with acute pneumonia and resulted in a fatal outcome in 5.1%. Infectious-toxic shock developed prevalently in males of young or middle age suffering of concomitant diseases in acute pneumonia due to viral-bacterial associations. At the pre-hospital period shock was detected only in 5.1% of patients due to inadequate examination, underestimation of symptoms and their erroneous interpretation. Clinical manifestations of infectious-toxic shock, their polymorphism may masquerade acute pneumonia symptoms and lead to diagnostic errors. PMID- 1759438 TI - [Thermography in assessing the microcirculation of patients with acute and chronic viral hepatitis]. AB - The important role is emphasized of microcirculatory disorders in the pathogenesis of viral hepatitis and the necessity of their early diagnosis. For this purpose the method of infrared thermography of the upper extremities (hands) was used that allowed to reveal pronounced disorders of the peripheral hemodynamics in a significant number of patients with acute and chronic viral hepatitis, in particular, hepatitis B that promoted a more severe, progressive course of the disease. It is concluded that for instituting pathogenetically substantiated treatment, prognosis and prevention of unfavourable outcomes it is necessary to supplement clinico-laboratory data by instrumental examination of the terminal blood flow, in particular, thermography of the extremities. PMID- 1759439 TI - [The pathogenetic and prognostic significance of the level of class-E immunoglobulins in erysipelas]. AB - The authors determined the content of total immunoglobulins of the E class in the blood plasma: native (IgE) and exhausted by a streptococcal allergen in the dynamics of the disease in 145 patients with erysipelas. The level of antistreptococcal reagins was evaluated. It was established that at the onset of erysipelas the concentration of IgE and a-IgE showed a short-term increase in 52 +/- 4% and 87 +/- 3% of patients correspondingly. During convalescence the level of these antibodies did not differ from that of the normal excluding high risk patients for recurrence. The participation of IgE-mediated type of allergic reactions in the pathogenesis of erysipelas is suggested. It is recommended to use the content of IgE and a-IgE for the prognosis of immediate and remote recurrences of erysipelas. PMID- 1759440 TI - [The phytotherapy of patients with arterial hypotension]. PMID- 1759441 TI - [Phytotherapy in digestive organ diseases]. PMID- 1759442 TI - [Enterosorbent SKN in the combined rehabilitative treatment of patients who have had a myocardial infarct]. AB - A study of 34 patients with 2-3 months history of myocardial infarction revealed that 10-day course of treatment with SKN enterosorbent resulted in normalization of lipid peroxidation and several indices of lipid metabolism. These changes were in a part of the patients accompanied by an increase of tolerance to physical load and reduced requirement of the myocardium in oxygen. PMID- 1759443 TI - [The significance of the ergometrine test for the diagnosis of ischemic heart disease and the choice of antianginal treatment]. AB - A study of 68 patients showed that the ergometrine test is a rather informative method of the diagnosis of ischemic heart disease that supplements essentially the results of loading tests. The authors demonstrate the possibility of using the ergometrine test with the purpose of evaluating the effect of antianginal therapy. PMID- 1759444 TI - [The clinical and treatment characteristics of patients with herpes zoster in different locations]. AB - An analysis is presented of the clinical course and results of treatment of 102 patients with herpes zoster. The spinal ganglia of the thoracic region and trigeminal nerve ganglia were most frequently involved. The disease was manifested not only in local disorders but also in generalized systemic vegetative-trophic and vascular disorders. The authors report a high therapeutic efficiency of complex treatment of patients with herpes zoster using antiviral, antiherpetic and detoxification agents, immunostimulators, vegetotropic drugs, physiotherapy and ointment applications. PMID- 1759445 TI - [The activity of superoxide dismutase and of the metabolites of lipid peroxidation in an acute inflammatory process]. PMID- 1759446 TI - [A case of exudative erythema multiforme (a clinico-immunological study)]. PMID- 1759447 TI - [The intravital diagnosis of a dissecting aneurysm of the ascending aorta complicated by hemopericardium]. PMID- 1759448 TI - An explanatory model of diabetes. PMID- 1759449 TI - Preterm infants' physiologic responses to early parent touch. PMID- 1759450 TI - The appraisal of pain and coping in cancer patients. PMID- 1759451 TI - Nurses' risk taking regarding HIV transmission in the workplace. PMID- 1759452 TI - Relationship between head nurse responses to staff nurses and staff nurse responses to patients. PMID- 1759453 TI - Real and ideal hospital work environments in juxtaposition. PMID- 1759454 TI - Predictive validity of examinations for assessing student nurses. PMID- 1759455 TI - Use of computers for nursing minimum data set and nursing home cost studies. PMID- 1759456 TI - Issues related to reliability of videotaped observational data. PMID- 1759457 TI - [Experiences with liver transplantation in hepatitis B antigen positive liver cirrhosis]. AB - From 1982 to January 1991 228 orthotopic liver transplantations (OLT) were performed in 213 patients with end-stage disease at the Vienna transplantation centre, 1st University Department of Surgery. 14 patients were serum HBV surface antigen (HBsAg) positive at the time of transplantation. In the first 4 patients only OLT was performed; postoperatively all grafts became reinfected and the patients developed chronic hepatitis. In a further series, immunoprophylaxis against hepatitis B virus reinfection was carried out with hyperimmuneglobulin. In 4 patients short-term immunoprophylaxis was performed; all of them were seronegative after OLT, but HBsAg ++reoccurred in the serum within 3-16 weeks after transplantation and all patients experienced reinfection of their graft. The 2 patients, who had been transplanted in a replicative state (HBeAg positive) showed a fatal course of hepatitis in the graft. Out of 6 patients given long term immunoprophylaxis 3 cases showed stable liver function, without any signs of reinfection, and the HBsAg negative status remained for up to 19 months after transplantation. Since two patients displayed a HBV replicate status prior to transplantation, alpha interferon was administered preoperatively, which resulted in decreased serum HBV-DNA levels. PMID- 1759458 TI - [Dysfunction of the sphincter of Oddi as a cause of so-called postcholecystectomy syndrome]. AB - In up to 30% of cases of the so-called postcholecystectomy syndrome functional disturbances of the sphincter of Oddi are responsible for the clinical picture. These pathological changes in pressure and motility at the sphincter can be identified by means of endoscopic manometry. We found dysfunction of the sphincter of Oddi in 4 out of 10 patients with so-called postcholecystectomy syndrome. In 2 patients in whom the basal pressure was higher than 40 mmHg endoscopic papillotomy was performed, after which the patients remained symptom free. In one case tachyoddi was diagnosed and in another case the proportion of retrograde sphincter contractions exceeded 50%. Endoscopic manometry at the sphincter of Oddi enables many of the as yet unclarified postcholecystectomy symptoms to be identified. PMID- 1759459 TI - [Endocrinologic function following cranial irradiation in acute lymphoblastic leukemia in childhood]. AB - Endocrinological function was evaluated in 31 children after successful treatment of acute lymphoblastic leukaemia. All patients had received combination chemotherapy and 12-24Gy of cranial irradiation according to the German therapy protocols BFM-81, BFM-83 and BFM-86. Height, weight, bone age and pubertal development, as well as hypothalamic-pituitary function were measured. Long-term linear growth was unaffected in all patients. However, 9 patients showed subnormal serum growth hormone levels in response to pharmacological stimulation of the pituitary. All patients had normal levels of T3 and T4, but one patient showed an increased response of thyrotropin to thyrotropin releasing hormone. All prepubertal and postpubertal children demonstrated appropriate secretion of follicle-stimulation hormone (FSH) and luteinizing hormone (LH) after stimulation with LH-releasing hormone (LH-RH). 3 pubertal girls showed adequate oestradiol levels, but abnormally high levels of gonadotropins in response to LH-RH. Sexual development was normal in two of them, but the third had a late menarche and irregular menses. The significance of these findings is discussed in the context of recommendations possibly to further reduce or completely delete prophylactic cranial irradiation. PMID- 1759460 TI - [Paul de Sorbait (1624-1691): on the 300th anniversary of his death]. AB - The life of Paul de Sorbait (1624-1691), who was Professor of Medicine, Dean of the Medical School, and Rector Magnificus at Vienna University, is reviewed on the occasion of the 300th anniversary of his death. PMID- 1759461 TI - [Low dosage long-term treatment with recombinant alpha interferon induces in hairy cell leukemia continuous complete remission]. AB - Long-term treatment with recombinant interferon alpha (IFN) leading to complete remission in a patient with hairy cell leukaemia is presented. Four months after the beginning of treatment with IFN, the parameters of the peripheral blood had normalized. In spite of a continuous dose reduction (to a dose of 1 Mio. U/week) remission could be maintained during the six years of treatment. Two years after the start of treatment with IFN, a metastasizing carcinoma of the prostate was diagnosed, leading to death after four years. With regard to the hairy cell leukaemia, the patient was free of symptoms and the obduction confirmed the complete remission: the histological examination of bone marrow, spleen, liver and lymph nodes showed no more signs of hairy cell leukaemia. This case report shows that long-term treatment with IFN in some cases is effective to induce and to maintain complete remission in hairy cell leukaemia. PMID- 1759463 TI - The challenge to health insurers. 'Medicina nusquam non est' (medicine is universal): VI. PMID- 1759462 TI - [Medicamentous modification of vascular tone in varicose vein patients: comparative study of venous compliance technique and digital photoplethysmography]. PMID- 1759464 TI - Where there's smoke, there's fire. PMID- 1759465 TI - Factors in the economics of health care. PMID- 1759466 TI - But it just looked like an insect bite .... A case of myrasis in Wisconsin. PMID- 1759467 TI - Ulnar neuropathy caused by an accessory abductor digiti minimi muscle. AB - Peripheral neuropathies of the ulnar nerve at various locations in the upper extremity are common, but compression of the ulnar nerve at the level of the wrist due to an anomalous muscle is rare, though reported in the literature. Three cases of an abnormal abductor digiti minimi origin were first reported by Wood in 1868, but no mention was made of an associated ulnar neuropathy. To data, there have been 8 reported cases of an anomalous abductor digiti minimi, with sensory or motor abnormalities of the ulnar nerve the most common presentation. This case report describes a patient who had subjective paresthesiae in the ulnar nerve distribution for 2 years. He was found, at exploration, to have an anomalous muscle belly originating proximally from the deep forearm fascia with insertion into the abductor digiti minimi. We present the case, discuss the spectrum of compression neuropathies of the ulnar nerve at the wrist, and a review of the occurrence of anomalous muscles responsible. PMID- 1759468 TI - Diagnostic dilemma for the 1990s: Lyme disease versus rheumatic fever. AB - A 15-year-old boy developed an annular erythematous skin rash, fever, knee pain, syncope, and was found to be in complete heart block requiring temporary transvenous pacing. His recovery was complete following therapy with high dose steroids, aspirin, and IV ceftriaxone followed by oral penicillin. Serologic tests documented diagnostic levels of antibodies to Borrelia burgdorferi as well as to Group A streptococcal DNase B. Diagnoses of both Lyme disease and rheumatic fever are based on clinical presentation and serologic confirmation. Our patient had a clinical presentation compatible with either diagnosis and serologic test results suggestive of infection by both B burgdorferi and Group A streptococci. The patient's management was aimed at preventing complications of both diseases, since clinicians involved with the patient's case could not agree on the most likely diagnosis. We present this case to emphasize the following: both rheumatic fever and Lyme disease should be considered in patients presenting with annular skin rashes and complete heart block; serologic studies may be confusing in both Lyme disease and rheumatic fever since neither is entirely sensitive nor specific and efforts should be made to document the causative organism by appropriate cultures, biopsies, and stains when possible; and improved immunoserologic testing for Lyme disease, in particular, is highly needed. PMID- 1759469 TI - ASSIST Wisconsin. PMID- 1759470 TI - News you need on Medicare. PMID- 1759471 TI - [Early diagnosis and treatment results in breast carcinoma--a population-based analysis]. PMID- 1759472 TI - [Changes in the surgical therapy of breast carcinoma against the background of a changing perspective in oncology]. PMID- 1759473 TI - [Treatment results in breast carcinoma within the interdisciplinary therapy concept of the Charite]. PMID- 1759474 TI - [Surgical therapy in non-invasive cancer of the breast]. PMID- 1759475 TI - [Radiotherapy following radical surgery--indications - technique - complications]. PMID- 1759476 TI - [Indications for radiotherapy in metastasizing breast carcinoma]. PMID- 1759477 TI - [Hormonal and chemotherapy of advanced breast carcinoma]. PMID- 1759478 TI - [Practical experiences with psychosocial rehabilitation in breast carcinoma]. PMID- 1759479 TI - [Medical requirements resulting from old military burdens]. PMID- 1759480 TI - [Dendritic spines and interneuronal integration. The problems and the prospects]. PMID- 1759481 TI - [The epiphysis and the organization of behavior]. PMID- 1759482 TI - [Noncontractile energy expenditure by transverse-striated muscle tissue]. PMID- 1759483 TI - [An analysis of the hypotheses on the mechanisms of the vagus acceleration of heart beats]. PMID- 1759484 TI - [The development of the hypothalamus in ontogeny. The differentiation of the neurosecretory neurons]. PMID- 1759485 TI - [Basal ganglia and sensory systems: the motor-sensory dependence]. PMID- 1759486 TI - [The reflex arches of the facial nucleus]. PMID- 1759487 TI - Adverse reactions after injection of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or pertussis components in the vaccine. AB - Reactions to adsorbed diphtheria-pertussis-tetanus (DPT) vaccine have mostly been attributed to the pertussis organisms or pertussis components in the vaccine. Nevertheless reactions may also be due to other factors such as sensitization induced by aluminium adjuvants and impurities present in crude toxoids that cannot be removed by purification of toxoids after formalinization. Aluminium compounds such as aluminium phosphate and aluminium hydroxide are the most commonly used adjuvants with vaccines for human use. Due to the increasing concern about the toxicity of aluminium, other adjuvants like calcium phosphate may be evaluated as an alternative to aluminium adjuvants. To minimize reactions after immunization with DPT vaccine due to impurities in the toxoids, the use of toxoided purified toxins is suggested. PMID- 1759488 TI - Final report of the Keystone AIDS vaccine liability project. The Keystone Center. PMID- 1759489 TI - Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats. AB - The formalin-inactivated Rift Valley fever virus (RVFV) vaccine, TSI-GSD-200, was administered subcutaneously to highly susceptible adult Wistar-Furth rats (LD50-1 p.f.u., ZH501 strain). Vaccine was administered on days 0, 7 and 28, the same time course used for at-risk personnel. Six months postimmunization, when the serum plaque-reduction neutralization titre (PRNT)80 had declined to low or undetectable levels, rats were challenged with 4.4 log10 p.f.u. of the virulent ZH501 strain in a nose-only dynamic aerosol apparatus. Ninety-seven per cent (33/34) of the non-vaccinated control rats died. In contrast, only 32% (33/105) of the vaccinated animals died. In vaccinated rats that succumbed, there was a doubling of the mean time to death and the cause of death shifted from hepatitis to encephalitis. Rats with a PRNT80 of greater than or equal to 1:40 were protected from clinical disease and histological evidence of hepatic or encephalitic lesions. While the precise mechanisms of immunity against aerosol challenge remain unresolved, here the serum PRNT titre correlated with protection. PMID- 1759490 TI - Physicochemical and immunological characterization of recombinant host-protective antigen (VP2) of infectious bursal disease virus. AB - Small fusions to the N-terminal end of the host-protective antigen (VP2) of infectious bursal disease virus lead to stable expression of VP2 in Escherichia coli and yeast, and reduce the levels of inclusion body formation in E. coli in comparison to VP2 constructs with larger N-terminal fusions. VP2 produced with small N-terminal fusions, like native viral VP2, can be fractionated into a high molecular weight 'multimeric' form and a monomeric form. A virus-neutralizing monoclonal antibody that only recognizes undenatured VP2 preferentially reacts with multimeric forms of recombinant VP2. Both native and recombinant monomeric forms of VP2 are non-immunogenic. The multimeric forms of viral and yeast-derived VP2 are highly immunogenic, while those produced in E. coli are not. PMID- 1759491 TI - Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18 month-old children. AB - The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis. PMID- 1759492 TI - Phase I clinical trial of an acellular pertussis vaccine composed of genetically detoxified pertussis toxin combined with FHA and 69 kDa. AB - An acellular pertussis vaccine composed of genetically detoxified pertussis toxin (PT-9K/129G), filamentous haemagglutinin (FHA) and pertactin (69 kDa protein) was evaluated in adult volunteers, in double blind, versus placebo. No fever was reported in either group. Mild local reactions were reported after injection of both vaccine and placebo. After the first dose a marked increase in antibodies to PT, FHA and 69 kDa protein was seen in vaccinated subjects with the exception of one who responded well to PT and FHA but did not show a humoral response to the 69 kDa protein. All vaccinees acquired cellular immunity against the three antigens. No significant variation was observed in the humoral or cellular responses after the second dose. PMID- 1759493 TI - Influenza immunization: intranasal live vaccinia recombinant contrasted with parenteral inactivated vaccine. AB - To compare the efficacy and duration of the immune response to local and systemic vaccination, Balb/c mice were vaccinated either intraperitoneally (i.p.) with an inactivated A/PR/8/34 (H1N1) vaccine or intranasally (i.n.) with a vaccinia recombinant containing the H1 gene of influenza. The i.p. inactivated vaccine stimulated high serum IgG anti-influenza titres and protected the lungs against viral challenge for the duration of the experiment (17 months). Little nasal wash IgA was induced and the noses were susceptible to challenge. Animals vaccinated i.n. with the recombinant had lower serum IgG titres and the lungs showed poor protection against challenge. Nasal wash IgA titres were higher, however, and the noses were largely protected from viral challenge for 17 months. PMID- 1759494 TI - Oral immunization with bacterial polysaccharide and adjuvant enhances antigen specific pulmonary secretory antibody response and resistance to pneumonia. AB - Nosocomial pneumonia, often due to Pseudomonas aeruginosa, occurs frequently after haemorrhage and trauma, and contributes to the increased incidence of morbidity and mortality in this clinical setting. In order to determine if enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs can increase resistance to P. aeruginosa pneumonia following haemorrhage, we investigated oral immunization strategies, using bacterial polysaccharides (levan, from Aerobacter levanicum, and P. aeruginosa polysaccharide type I) and adjuvant (cholera toxin and the B-subunit of cholera toxin), capable of increasing bacterial polysaccharide-specific pulmonary secretory antibody titres. Oral co-administration of 1000 micrograms levan and 10 micrograms cholera toxin resulted in increased titres of levan-specific sIgA in lung lavages and increased numbers of levan-specific pulmonary plasma cells, but no changes in serum anti levan titres. Similarly, oral co-administration of 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin produced increased anti-P. aeruginosa polysaccharide titres in lung lavages. Significant decreases in anti levan pulmonary sIgA titres and in numbers of levan-specific pulmonary plasma cells were found when oral immunization with levan and cholera toxin was performed 4 days following haemorrhage, but not if the mice were immunized 8 h after blood loss. Although haemorrhage markedly increased the susceptibility of mice to P. aeruginosa pneumonia, significant protection from mortality could be achieved through oral immunization with 1000 micrograms P. aeruginosa polysaccharide and 10 micrograms cholera toxin 8 h after haemorrhage. These results demonstrate that haemorrhage induces marked alterations in bacterial antigen-specific pulmonary B-cell responses, which contribute to the increased susceptibility to infection in this setting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759495 TI - Controlled release microparticles for vaccine development. AB - The primary and secondary sera IgG antibody responses to ovalbumin (OVA) entrapped in biodegradable poly(lactide-co-glycolide) (PLGA) microparticles were compared with the responses obtained with soluble OVA. In addition, OVA in PLGA microparticles was also administered after dispersion in an immunostimulatory vehicle, Freund's incomplete adjuvant (FIA). The primary IgG responses to OVA in microparticles/FIA were significantly greater than the responses to soluble OVA from day 14 to day 42, when booster immunizations were administered. From day 49 to the end of the study at day 84, the responses to OVA, both in microparticles alone and in microparticles/FIA, were significantly greater than the responses to soluble OVA. Nevertheless, the responses obtained for OVA in microparticles or microparticles/FIA were, in general, not as high as those obtained with OVA in Freund's complete adjuvant. PMID- 1759496 TI - HIV vaccines. PMID- 1759497 TI - The quest for vaccines against AIDS: progress and challenges. An overview. PMID- 1759498 TI - The challenge of HIV vaccines. AB - Immunization of an animal or human being against an infectious agent provides levels of protection that are relative only. Protection can be overcome by high challenge doses. Even with a low challenge dose, protection can vary from absolute to relative. The invading pathogen may be neutralized and eliminated from the body before it can multiply; in this case, immunization provides protection against infection. More frequently, the infectious agent starts multiplying at the site of entry, which triggers an anamnestic immune response of the host. Rejection of the invader usually takes place before the appearance of overt clinical symptoms; in this case, immunization provides protection against disease. Protection against infection implies a strong pre-existing immune barrier. Protection against disease mostly relies on immune memory and the possibility for the host of mounting a rapid immune response against the infectious agent. PMID- 1759499 TI - Are we detouring from a direct route to development of HIV vaccines? AB - Experiments in animal model systems have demonstrated that it is possible for vaccination to elicit immune responses that can prevent or significantly delay lentiviral infection and perhaps disease. To facilitate the development of effective HIV vaccines, current research and development efforts must utilize the appropriate HIV strains. International scientific communities and vaccine manufacturers, with the support of governments, should now unite to ensure that the most direct route possible will be taken. PMID- 1759500 TI - SIV vaccines: current status. The role of the SIV-macaque model in AIDS research. AB - SIV vaccines made of inactivated whole virus, modified live virus and native and recombinant envelope antigens have protected macaques against experimental infection with low doses of cell-free SIV given systemically. The few vaccinated monkeys that do become infected have tended to live longer than the infected controls. Protection against cell-associated virus has not as yet been tested. The recombinant envelope vaccines now on test have generally not been as effective as the whole virus vaccines. Post-infectious immunotherapy with SIV vaccines has been ineffective. The same whole virus and modified live virus vaccines that protect against systemic infection fail to protect against genital mucosal challenge with cell-free virus. Since sexual transmission is the major route of HIV spread on a global scale, a major effort is now required to develop vaccines in this animal model that induce genital mucosal as well as systemic immunity against infection with both cell-free and cell-associated SIV. PMID- 1759501 TI - Prospects for AIDS vaccines: the need for clinical trials in human populations. PMID- 1759502 TI - Internal image (Ab2 beta) anti-idiotype vaccines. Theoretical and practical aspects. AB - Anti-idiotype antibodies that carry an internal image of an antigen epitope (Ab2 beta antibodies) can be used in vaccine preparations to favourably manipulate the immune network. These vaccines have been shown to induce protective immunity in animals that have not been intentionally exposed to the native antigen epitope. This review attempts to define certain theoretical and practical aspects of immunological network manipulations and their relevance to Ab2 beta internal image anti-idiotype antibody vaccine design. PMID- 1759503 TI - Construction of genetically defined double aro mutants of Salmonella typhi. AB - The construction of genetically defined, double aro mutant strains CVD906 and CVD908, which were derived from Salmonella typhi strain ISP1820 (a recent isolate of S. typhi from Chile) and from laboratory strain Ty2, respectively, is described. Strains CVD906 and CVD908 differ from previously described aro mutants of S. typhi as their aro deletion mutations do not extend beyond the limits of the mutated aro genes, and no antibiotic-resistance genes, plasmid sequences or S. typhimurium DNA sequences remain in the mutant strains. In minimal medium the aro mutants of S. typhi are unable to replicate whereas the wild type parent strains grow well in minimal medium. Using intraperitoneal inoculation of mice with S. typhi strains suspended in hog gastric mucin as a virulence assay, it is shown that the single aro mutants and the double aro mutants of Ty2 and ISP1820 are attenuated in mice. Trans complementation of the aro mutants with the aroC gene or aroD gene, or both, results in strains that are phenotypically identical to that of the wild type parents indicating that no measurable additional changes other than loss of the aro gene function occurred during strain construction. PMID- 1759504 TI - The effect of cholera toxin and cholera toxin B subunit on the nasal mucosal membrane. AB - The effects of the self-adjuvanting substances, cholera toxin (CT) and cholera toxin B subunit (CTB), on rabbit nasal mucosal membrane, were investigated by using Ussing chambers. The control nasal mucosa (lateral wall), isolated from rabbits and mounted in the chamber, showed transepithelial potential difference, short-circuit current and conductance of -10 mV, 200 microA cm-2 and 20 mS cm-2, respectively. These parameters were compared with mucosa isolated from human inferior conchae, showing that rabbit nasal mucosa may be usable to understand effects on human mucosa. When the mucosa was exposed to various concentrations of CTB and CT, the short-circuit current and conductance of the mucosa increased with increasing concentration. CTB showed gradual increase in the short-circuit current when added in the same molar concentration as the B subunit contained in CT, which caused drastic changes by increasing the current to infinite value. Furthermore, the total amount of transepithelially fluxed CTB, which occurred rapidly after addition to the mucosal side of the chambers, increased with increasing CTB concentration. On the other hand, less flux was observed after addition of CT. These changes could be blocked by addition of ganglioside GM1. This demonstrates that the effect of CTB on the rabbit mucosal membrane are different from those of CT, although both CT and CTB act specifically on the membrane via the CTB receptor, ganglioside GM1. PMID- 1759505 TI - Pre-exposure rabies prophylaxis for travellers: are the benefits worth the cost? AB - Pre-exposure rabies prophylaxis is recommended by the Immunization Practices Advisory Committee of the US Public Health Services (PHS) as a safe and effective method for reducing the risk of rabies in international travellers. The United States Peace Corps provides pre-exposure prophylaxis with human diploid cell rabies vaccine (HDCV) to over 2000 new volunteers each year going to rabies endemic countries. During the year November 1987 through October 1988, 175 rabies exposures (and no deaths) were documented in Peace Corps Volunteers serving in 31 rabies-endemic countries, for an overall postexposure treatment rate of 43.6/1000 volunteers per year. Although PHS treatment protocols were strictly followed, the postexposure prophylaxis rate for these Peace Corps Volunteers was 550 times higher than that for the US general population, and 55 times higher than the average rate for 30 developing countries. The use of pre-exposure prophylaxis in travellers was not cost-effective and will not become so until the price of a dose of vaccine declines substantially to $7.00 for the Peace Corps, and even lower for groups with less rabies exposure. However, despite the high vaccine cost, pre-exposure prophylaxis continues to be recommended in the Peace Corps for important non-economic reasons which may also be applicable to other groups of travellers. PMID- 1759506 TI - Immunity to diphtheria in the 3-19 year age group in Italy. AB - In Italy, immunization with diphtheria toxoid has been compulsory for all newborns since 1939. The last two clinical cases of diphtheria were reported in 1987. During the period 1987-1989, immunity against diphtheria was assessed by neutralization test in a random sample of 1740 healthy subjects 3-19 years old, from five geographical areas of Italy. Of the total population, 76.5% showed antibody levels considered to be protective (greater than or equal to 0.1 IU ml 1), 17.2% had a relative degree of protection (0.01-0.09 IU ml-1), and 6.3% lacked immunity (less than 0.01 IU ml-1). The percentage of unprotected subjects increased from 6.1% in the age group of 3-5 years to 11.4% in the age group of 18 19 years (p less than 0.01). A smaller proportion of males (5.3%) than of females (7.2%) was unprotected, but this difference was not statistically significant. Subjects residing in the south and the islands were more likely to be unprotected than those residing in the north (7.4 versus 4.1%, p less than 0.01). No association was found between lack of protective antibodies and family size (odds ratio 1.35, confidence interval 95% = 0.77-2.36). However, paternal education of less than 12 years was associated with a higher prevalence of non-responders. In order to maintain a high degree of immunity in the adult population, a routine adult booster dose of diphtheria toxoid is advisable. PMID- 1759507 TI - Nucleotide sequence analysis of Urabe mumps vaccine strain that caused meningitis in vaccine recipients. AB - Mumps virus was isolated from the cerebrospinal fluid of eight patients who acquired meningitis within 4 weeks of immunization with live Trivirix vaccine that contains mumps (Urabe Am 9), measles (Schwarz), and rubella (RA 27/3) viruses. Part of the haemagglutinin-neuraminidase (HN) gene from three postvaccination isolates of mumps virus, three wild strains and the Urabe and Jeryl Lynn vaccine strains was cloned following polymerase chain reaction (PCR) amplification, for the purpose of sequence analysis. A 200-nucleotide portion of the cloned HN genes was sequenced and compared to published sequences of two other strains (RW and SBL-1). The postvaccination mumps strains were identical in sequence to Urabe and were distinguishable from the wild and the Jeryl Lynn vaccine strains. Twenty-two out of 200 positions were seen to vary among the group of viruses. It was concluded that the Urabe vaccine strain was the cause of postvaccination meningitis. Therefore, with effect from 1990, Trivirix measles, mumps and rubella vaccine is no longer licensed for sale in Canada. PMID- 1759508 TI - Determination of circulating antibodies directed to pertussis toxin and of agglutinogens in children vaccinated with either the whole cell or component pertussis vaccine in France, Japan and Senegal. AB - The antibody response to pertussis toxin (PT) and agglutinogens of children vaccinated in Japan, France and Senegal with either whole cell or component pertussis vaccine was determined at various times after immunization. Agglutinin titres were almost similar in sera of Japanese children vaccinated with either whole cell or component pertussis vaccine whereas anti-PT antibody levels were found to be higher after vaccination with whole cell vaccine than with component vaccine. The geometric mean (GM) agglutinin titres in sera of Japanese children amounted to 45.0 and 45.7, respectively, and neutralization GM titres to 71.6 and 22.6, respectively, following vaccination with the whole cell and component pertussis vaccines. Sera of French children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 17.8, whereas only 16% of sera contained neutralizing antibodies against PT. Following the booster dose the GM agglutinin titre rose to 213.5 and 68% of the sera contained neutralizing antibodies to PT (GM titre 48.0). Sera of Senegalese children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 18.7, whereas anti PT neutralizing antibodies were hardly detected. Agglutinins and anti-PT antibody in sera of French and Senegalese children turned out to be lower than were found 25 years ago in sera of children immunized with the French whole cell pertussis vaccine. PMID- 1759509 TI - [Selective and routine use of mediastinoscopy for staging of bronchial cancer]. AB - Because of low rate of mediastinal lymphnode metastases of lung cancer in patients who seem to be able to undergo operative treatment, in most clinics mediastinoscopy for preoperative assessment is only used selectively when lymphnodes were found by CT before. Even though most US- and Canadian clinics use mediastinoscopy staging preoperatively because of differing sensitivity in CT. Analysis of CT and mediastinoscopy will be made by a special computer-program. It is focused that in T1 and T2 lung cancer selective mediastinoscopy is in favour. In T3 and T4 cancer mediastinoscopy should still be routine in the evaluation of mediastinal nodes for preoperative assessment. PMID- 1759510 TI - [Effect of perioperative allogenic blood transfusion on prognosis of colorectal cancer]. AB - In 1973 the observation was published that in patients who had received non specific blood transfusions before kidney transplantation graft survival was improved. An immunosuppressive effect of blood transfusion was suggested. Indeed, modulation on the cellular and humoral immunologic system has been demonstrated during the last decade. But this immunomodulation effect might worsen the prognosis after cancer surgery. Whereas in several experimental studies in animals the negative influence was confirmed, clinical investigations on the other hand are contradictive. In our retrospective study we analysed the follow up of 273 patients (158 men, 115 women; average age 66 years) on which we had performed a curative resection of their colorectal carcinoma. 182 patients had received nonspecific random blood transfusions. The survival rate for patients with blood transfusions was significantly worse in comparison to the non transfused group (43% versus 73%, respectively). Even when we subdivided our patients into tumor stage, differentiation and localisation, the negative influence of transfused blood was confirmed. We conclude that beside the risk of transmitting hepatitis or HIV the immunosuppressive effect is a strong argument to restrict the indication for blood transfusion. PMID- 1759511 TI - [Diagnosis of leiomyosarcoma of the colon after natural excretion]. PMID- 1759512 TI - [The cultural properties and virulence of Yersinia]. AB - Study of the cultivation properties of 82 enterobacterial strains has revealed that the colonies of virulent Y. enterocolitica (serovars O3, O9) and Y. pseudotuberculosis (serovar I) are temperature-sensitive. This sign, closely connected with the presence and expression of the virulence plasmid with a molecular weight of 44-48 MD, is not characteristic of other strains. Virulent Yersinia grown in nutrient agar for 48 hours at 37 degrees C form colonies which are smaller in diameter than those formed during cultivation at 26 degrees C (with the significance of differences t greater than or equal to 4), their diameter at 37 degrees C not exceeding 1.0 mm. The test for the determination of the temperature-sensitive morphology of Yersinia colonies, along with the tests for other virulence markers, is probably suitable for the detection of the causative agents of yersiniosis or pseudotuberculosis. PMID- 1759513 TI - [The development of intestinal dysbacteriosis in sexually mature rats after thymectomy]. AB - Thymectomy in puberal rats resulted in the development of pronounced enteric dysbacteriosis, correlating with the degree of T- and B-lymphocyte deficiency in the lymphoid organs and the blood stream during the first 2 months. Microbiocenosis restores probably due to more intensive functioning of alternative regulating mechanisms. A simple and informative characteristic indicating the degree of dysbacteriosis developing in the intestine is proposed: the index of dysbacteriosis. PMID- 1759514 TI - [The possibility of creating a vaccinal strain of Brucella abortus 19-BA with multiple antibiotic resistance]. AB - The possibility of preparing B. abortus vaccine strain 19-BA with multiresistance to antibiotics was shown. The strain was obtained by the spontaneous induction of resistance to rifampicin with the subsequent transformation of nonconjugative hybrid plasmid pOVI which, in addition to rifampicin resistance, governed the resistance of brucellae to tetracycline, doxycycline, ampicillin, and streptomycin. Experiments on guinea pigs demonstrated the immunization with both multiresistant vaccine strain GSA1 and B. abortus initial vaccine strain 19-BA. PMID- 1759515 TI - [The effect of leukinferon on the activity of phagocytosing cells in human salmonellosis]. AB - The functional activity of phagocytic cells in 52 salmonellosis patients was studied with regard to the following characteristics: percent share of phagocytosis, phagocytic index, nitro blue tetrazolium test results, digestive activity. In patients with the unfavorable course of salmonellosis (the formation of carrier state) disturbances in the bactericidal activity of neutrophils and monocytes were established. For 32 patients leukinferon was included in the complex of etiotropic and pathogenetic treatment. The preparation was introduced in 3 intramuscular injections of 10,000 I. U. at intervals of 48 hours (the course of treatment); 10 days after the last injection this course was repeated. The use of leukinferon restored the normal functioning of phagocytes and the number of T-lymphocytes. PMID- 1759516 TI - [The microfloral status of the intestines in people in contact with different antimicrobial preparations]. AB - The state of enteric microbiocenosis in persons having contacts with different antimicrobial preparations, depending on the spectrum of such preparations and the duration of the contact, has been studied. Dysbiotic disturbances in enteric microflora have been detected even in those who have daily short-term contacts with antibacterial preparations. PMID- 1759517 TI - [Hospital strains of Pseudomonas aeruginosa in the surgical clinic]. AB - Circulation of different antigenic variants of P. aeruginosa in a surgical hospital was studied. In this study the process leading to the formation of pathogenic hospital strains, determined by time and location, from some serovars is demonstrated. The study also established that the department of the hospital where the selection of hospital strains mainly occurred was the resuscitation ward. Some pyoseptic infections of P. aeruginosa etiology with fetal outcome were found to be caused in most cases by hospital strains characteristic of the hospital in the period under study. PMID- 1759518 TI - [The use of the cluster selection method for assessing the status of immunity to controlled infections (measles, diphtheria and tetanus)]. AB - The use of the method of cluster selection in mass serological examination makes it possible to obtain statistically significant results with very low expenditures. The coincidence of the results on the number of seronegative children, obtained by the method of cluster selection, with the results of mass serological examination of all children aged 6-7 years in the district (children found to be seronegative to measles constituted 5.5% and 5.0% respectively) is indicative of the statistical significance of the method used in this investigation. The results obtained by the method of cluster selection indicate that the level of protection among the children of the district was high both with respect to measles (94.5 +/- 1.8%) and tetanus (96.5 +/- 1.7%); with respect to diphtheria, the immune stratum was found to be less (91.1 +/- 2.3%). These data may be helpful in working out scientifically substantiated administrative decisions contributing to an increase in the effectiveness of planned mass immunization. PMID- 1759519 TI - [The use of computers and mathematical methods for optimizing epidemic control measures with respect to measles infection]. AB - The potentialities of computers for the study of the effectiveness of immunization have been demonstrated and the mathematical model for the prediction of the proportion of children, seronegative to measles, derived on the basis of the data on the average measles morbidity in different groups for a given period. A multifactor analysis of a large scope of data obtained in seroepidemiological survey and a retrospective analysis of measles morbidity on the basis of data collected in two districts of Moscow have been carried out with the use of computers and mathematical methods. PMID- 1759520 TI - [An evaluation of the status of natural foci of Crimean-Congo hemorrhagic fever in the Crimea]. AB - Parasitological data, the results of virological and serological investigations of materials, collected in nature and during the study of the immune structure of the population and indicative of the circulation of CCHF, virus in the Crimea and the possibility of human infection, are presented. The data on the spontaneous CCHF virus infection of 4 tick species belonging to the genus Ixodes have been confirmed, and evidence on the participation of Dermacentor marginatus in this process obtained for the first time in this region. The study has revealed for the first time that, besides European brown hares, scilly shrews, common voles and field mice may contribute to the maintenance of the natural foci of this infection. The low activity of the Crimean focus of CCHF may be the result of the intensive use of land, the widely spread stall-feeding of cattle, as well as a sharp decrease in the number of hares on the territories of hunting preserves. PMID- 1759521 TI - [An experimental study of Yersinia in plants]. AB - Y. enterocolitica and Y. pseudotuberculosis have been experimentally found to penetrate into plants (cabbage, salad, pea, oat) from infected soil and water and to remain in different plant organs (roots, seeds, leaves) up to 30 days (the term of observation). The processes of S-R dissociation in Yersinia cultures isolated from plants, as well as changes in some enzymatic properties, have been established. In the test on Infusoria the cytotoxic action of strains isolated from plants has been noted. The possible role of plants in carrying pathogenic bacteria from the soil to the surface ecological systems and the subsequent infection of animals and humans is discussed. PMID- 1759522 TI - [A safety and reactogenicity study of experimentally produced batches of the brucellosis chemical vaccine with different methods for its application]. PMID- 1759523 TI - [An experimental study of a lactoglobulin preparation against opportunistic bacteria and salmonellae]. AB - A preclinical study of seven batches of lactoglobulin, a new biological preparation against opportunistic bacteria and salmonellae, has been carried out. High antibacterial activity of the preparation with respect to the virulent forms of Salmonella typhimurium, Salmonella enteritidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis has been established. The preparation has been shown to be safe and nontoxic. The 4-year term of its storage at a temperature of 6 degrees +/- 4 degrees C has been substantiated. PMID- 1759524 TI - [The dynamics of the immunological indices during the treatment of recurrent erysipelas with the new immunostimulant bemitil]. AB - Bemitil, administered orally in a dose of 0.25-0.5 g a day for 5-7 days at the acute period of the relapse of erysipelas as an immunostimulant, enhanced the effectiveness of the basic therapy including antibiotics, anti-inflammatory and antiallergic drugs, vitamins, plasma-substituting fluids and saline solutions, as well as ultraviolet irradiation of the focus of lesion. Bemitil therapy was associated with an increase in the number of T-lymphocytes, normalization of the balance between the peripheral lymphocyte preparations, an increase of blood serum levels of IgA and IgM. PMID- 1759525 TI - [The production of specific immunoenzyme conjugates to human immunoglobulins by the glutaraldehyde method]. AB - The results of studies aimed at obtaining class-specific conjugates to human immunoglobulins to be used in the enzyme immunoassay (EIA) are presented. At the first stage of the studies purified IgA, IgM and IgG preparations were obtained. These preparations were used for obtaining immunologically active immunosorbents on the basis of bromocyanic Sepharose. Specific antibodies to human IgA, IgM and IgG were isolated from animal sera by the method of affinity chromatography. These antibodies were conjugated with peroxidase by the glutaraldehyde method. The specific activity of the conjugates were determined in EIA. The results thus obtained revealed that all preparations exhibited high specific activity and gave no cross reactions with immunoglobulins of other classes. PMID- 1759526 TI - [The characteristics of Staphylococcus aureus peptidoglycan in the spectrum of the reactivity of human lymphocytes to bacterial peptidoglycans]. AB - The sensitivity of lymphocytes of healthy persons to S. aureus peptidoglycan as compared with that to the polyclonal stimulator zymosan C3b and peptidoglycans of other bacteria (Streptococcus faecalis, Escherichia coli, Bacterium bifidum) was analyzed with a test system permitting the determination of specific reactivity to peptidoglycans. The analysis showed that at the peak of luminol-dependent chemiluminescence (25-30 minutes) individual reactivity to S. aureus peptidoglycan varied within wide limits (the coefficient of lymphocyte stimulation was 1.4-9.6, 3.5 +/- 0.6), exceeding sensitivity to other bacteria, as well as the values obtained in the negative control. The conclusion of the wide spread of sensitization to S. aureus peptidoglycan and the possibility of using this preparation for the study of cell-mediated immunity reactions was made. PMID- 1759527 TI - [Multispecific monoclonal antibodies]. AB - Immunization of BALB/c mice with Rickettsia prowazekii antigens, Bordetella pertussis toxin and Legionella pneumophila cytolysin induces the synthesis of IgM autoantibodies of different specificity. Among monoclonal antibodies, multispecific antibodies with a wide reactivity spectrum have been found to make up high percentage (30-80%). Monoclonal antibodies interact with different bacterial antigens and tissue substances. A hypothesis has been put forward that normally the injection of the antigen is followed by the appearance of antigen nonspecific "immunological noise", including the synthesis of both tissue specific and multispecific autoantibodies. Such antigen nonspecific "immunological noise" must have a certain threshold level which can be determined with the use of hybridoma techniques. This problem is particularly topical for bacterial antigens, as many of them are used in the development of vaccinal preparations, which may lead to an increase in the synthesis of autoantibodies and induce different autoimmune disturbances in the body. PMID- 1759528 TI - [The course of experimental staphylococcal sepsis in opposite mouse strains and first-generation hybrids]. AB - The survival time and histological lesions of the kidneys, liver, heart, and lungs were studied in CBA/Sto, C3HA/Mv and F1 (C3HA/Mv x CBA/Sto) mice for 15 days after i.v. injections with S. aureus pathogenic strains CFU B-243 in doses of 10(9), 10(8) and 2.5 x 10(8) microbial cells. CBA/Sto mice were found relatively resistant and C3HA/Mv mice, susceptible to infection caused by different doses of S. aureus, this being associated with different morphological picture in the viscera. F1 hybrids were at least as susceptible to the infections as any of the parent strains, suggesting recessive inheritance of resistance to staphylococcal infection. PMID- 1759529 TI - [A mathematical model of the growth of a population of Legionella pneumophila in the presence of Tetrahymena pyriformis protozoa]. AB - The mathematical model describing the dynamics of the growth of L. pneumophila in aqueous environment in the presence of protozoa has been worked out. The model has demonstrated considerable heterogeneity of the initial population of virulent L. pneumophila strains. The number of bacteria capable of multiplication in Infusoria is no more than 0.1% of the initial population. The time of the generation of the infective agent inside Tetrahymena pyriformis is 2.8 hours. PMID- 1759530 TI - [The host reaction to the administration of different components of Coxiella burnetii]. AB - After the intraperitoneal injection of corpuscles of C. burnetii antigen (Ag), phospholipid (PL), and sediment obtained after the extraction of PL from Ag with chloroform-methanol (CM) slight leukocytic reaction developed in the peritoneum on day 1, and on day 2 it could be observed in the liver and in the spleen. Ag induced the most pronounced morphological changes. In the spleen they were manifested by the activation of T- and B-dependent zones of white pulp from day 2 and by the pronounced hyperplasia of reticular cells and macrophages, leading to splenomegaly, by days 7-14. Simultaneously lymphoid-macrophagal granulomas and hepatomegaly developed in the liver. By days 7-14 the foci of necrosis in the liver were caused by the thrombosis of portal veins and were not registered after the injection of PL and CM (and earlier also in experiments with Ag in doses of 0.1-0.3 mg). PMID- 1759531 TI - [The dynamics of the basic factors of nonspecific resistance in North Asian tick borne typhus]. AB - At the acute period of tick-borne typhus an increase in the activities of the main nonspecific resistance factors of the body, and particularly lysozyme, betalysins, complement and properdin, is observed. During convalescence the concentration of lysozyme normalizes and the content of betalysins remains sufficiently high, this indicating that, even in the absence of clinical sings of the disease, the disturbances in homeostasis persist. A decrease in the levels of complement and properdin during convalescence is seemingly linked with their consumption for the formation of immune complexes, eliminated from the body. PMID- 1759532 TI - [The control of viral diseases in the developing countries with the use of existing vaccines]. PMID- 1759533 TI - [The adhesive and colonizing properties of Aerococcus viridans]. AB - On the basis of experiments carried out in the course of this study the conclusion can be made that one of the mechanisms of the preventive effect of aerococci, the representatives of the indigenous microflora of the gastrointestinal tract, lies in their capacity for adhesion to and colonization of the mucous membrane, this enhancing the resistance of the enteric tract to infections. These properties of anterococci substantiate good prospects of using M-bacterin (live lyophilized aerococcal culture) for the control of enteric infections and dysbacteriosis. PMID- 1759534 TI - Long-term growth hormone treatment in growth hormone deficient adults. AB - Growth hormone treatment in GH-deficient adults has proved beneficial in recent short-term trials, but long-term results have not yet been reported. Thirteen GH deficient adults (4 females, 9 males; mean (SEM) age 26.4 (1.7) years), who had completed 4 months of GH therapy in a double-blind placebo-controlled cross-over study were followed, for further 16.1 (0.8) months of uninterrupted GH therapy in an open design. A significant mean increase of 1.3 cm in linear height was recorded, whereas body mass index remained unchanged. Mean muscle volume of the thigh, estimated by computerised tomography, increased significantly compared with that of the initial placebo period (p = 0.01), and a slight decrease was recorded in adipose tissue volume of the thigh (p = 0.10) and subscapular skinfold thickness (p = 0.10). Still, the muscle to fat ratio of the thigh was significantly lower compared with that of normal subjects (72.6/27.4 vs 77.9/22.1) (p less than 0.01). The mean isometric strength of the quadriceps muscles increased significantly during long-term GH therapy (p less than 0.01), but remained lower compared with that of normal subjects (1.66 (0.10) vs 2.13 (0.11) Nm/kg body weight). Exercise capacity performed on a bicycle ergometer increased significantly after long-term therapy (p less than 0.05), but still did not reach the values seen in normal subjects (22.5 (3.4) vs 37.4 (4.2) watt.min.kg-1. No adverse reactions were recorded during long-term therapy and hemoglobin A1c remained unchanged. These data suggest that long-term GH replacement therapy in GH-deficient adults has beneficial effects on several physiological features which are subnormal in these patients. PMID- 1759535 TI - The neuropeptide, head activator, in human placenta and serum from pregnant women. AB - The hydra neuropeptide, head activator, was detected in human placenta using radioimmunoassay. The placenta contained 11-68 fmol/g wet weight of head activator. The slope of the inhibition curve by placental extract in radioimmunoassay was identical to that of synthetic head activator. The molecular weight of the major immunoreactive head activator in placental extract corresponded to the synthetic head activator after Bio-Gel P-2 column chromatography. The peak of immunoreactive head activator in the extract emerged at the same retention time as that of the synthetic head activator on reversed phase high-performance liquid chromatography. Head activator was localized histologically in trophoblasts of placenta by peroxidase-antiperoxidase staining techniques. The head activator staining was inhibited by the excessive synthetic head activator. The serum head activator level during pregnancy ranged from 9 to 31 pmol/l. A positive linear correlation was found between serum head activator content and gestational weeks. PMID- 1759536 TI - Regional stimulation of thyroid epithelial cells in Graves' disease by lymphocytic aggregates and plasma cells. AB - The significance of intrathyroidal lymphocytic infiltration is not known. However, several indirect lines of evidence suggest that interstitial or intraepithelial lymphocytes are the effector or thyroid autoantibody-producing lymphocytes in Graves' disease. This has not been investigated in vivo. Changes of nuclear volume of endocrine cells have previously been shown to be a reliable parameter of functional stimulation of endocrine glands. Therefore we investigated this parameter near and off lymphocytic aggregates, loosely distributed plasma cells and memory T cells in paraffin sections of Graves' disease thyroid glands. In 21 Graves' disease thyroid glands we found significant increases of thyroid epithelial cell nuclear volume near plasma cells (198.4 micron3) as well as near lymphocytic aggregates (219.1 micron3) compared with thyroid epithelial cell nuclear volume one microscopic field away (160.1 and 137.7 micron3 respectively). Similar nuclear volume differences were observed after propanolol and thiourelene antithyroid drug treatment. These nuclear volume differences could not be observed in 10 control thyroid glands and around CD45R0 positive memory T cells in Graves' disease thyroid glands. These direct in vivo investigations of regional functional stimulation of thyroid epithelial cells in Graves' disease show local stimulation near lymphocytic aggregates and diffusely distributed plasma cells. Therefore our in vivo data do not permit to identify stimulatory lymphocytes only interstitially or intraepithelially as previously suggested. PMID- 1759537 TI - Failure to confirm a growth hormone-releasing activity of corticotropin-releasing hormone in acromegaly: comparison with the effects of other hypothalamic hormones. AB - We re-examined whether CRH stimulates GH secretion in acromegaly. Human CRH (100 micrograms) was given as an iv bolus to 15 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. For comparison, we assessed in all the patients the effects of TRH (500 micrograms), GnRH (100 micrograms), vasoactive intestinal peptide (100 micrograms) and peptide histidine methionine (100 micrograms), which are known paradoxically to stimulate GH secretion in acromegaly. A paradoxical GH response (greater than 50% above the basal) to TRH, GnRH, vasoactive intestinal peptide and peptide histidine methionine was observed in 12 (80%), 4 (27%), 5 (33%) and 2 (13%) patients, respectively. All the patients were responsive to at least one of these 4 peptides. However, none of the patients showed a positive GH response to hCRH. These results do not support a GH-releasing activity of CRH in acromegaly. Even if CRH has such an effect, it does not appear as potent as TRH, GnRH, vasoactive intestinal peptide and peptide histidine methionine. However, the possibility cannot be excluded that our negative data might have been due to the use of hCRH vs ovine CRH in earlier studies. PMID- 1759538 TI - Thyrotropin receptor antibodies following treatment with recombinant alpha interferon in patients with hepatitis. AB - We measured thyrotropin receptor antibodies in serum obtained from 2 groups of patients participating in clinical trials of recombinant interferon-alpha 2b for viral hepatitis. Group I: Patients with hepatitis B (N = 8), received interferon 5 x 10(6) units thrice weekly for 4 months. Group II: Patients with non-A, non-B hepatitis (N = 16) were randomized to receive interferon in a dose of either 0.25 x 10(6) or 3 x 10(6) U thrice weekly for 6 months and then crossed over to receive the other dosage schedule for a further 6 months. None of the patients developed thyrotoxicosis. Thyrotropin receptor antibody activity was detectable within the "normal range" (less than 10 U/l) in 6 patients prior to treatment. In Group I, thyrotropin receptor antibodies became detectable in 6 patients on treatment, in 4 of whom it was 10 U/l. In Group II, thyrotropin receptor antibody activity was unchanged on low-dose interferon, but on the higher dose became detectable in 9 patients, in 7 of whom it was greater than 10 U/l. We conclude that treatment with interferon is associated with the development of thyrotropin receptor antibodies in a large proportion of patients. It is possible that in some patients treated with higher doses of interferon the increase in thyrotropin receptor antibody activity may be sufficient to induce hyperthyroidism. PMID- 1759539 TI - Chronic treatment with parlodel LAR of patients with prolactin-secreting tumours. Different responsiveness of micro- and macroprolactinomas. AB - Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR, Sandoz), 25-100 mg (mostly 50 mg) in every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p less than 0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p less than 0.05) in macro- than in microprolactinoma patients. IN CONCLUSION: a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine. PMID- 1759540 TI - Effects of exogenous growth hormone pretreatment on the pituitary growth hormone response to growth hormone-releasing hormone alone or in combination with pyridostigmine in type I diabetic patients. AB - We evaluated the effects of iv pretreatment with exogenous GH on the GH response to GHRH either alone or in combination with pyridostigmine in 14 Type I diabetic patients and 6 normal subjects. All the subjects received an iv bolus injection of biosynthetic human GH, 2 IU; 2 h later they received either a. pyridostigmine, 120 mg orally, or b. placebo, 2 tablets orally, followed 1 h later by iv injection of GHRH(1-29) NH2, 100 micrograms. In normal subjects the median GH peak after GH+ GHRH was 1.8, range 1.2-6.9 micrograms/l. Pyridostigmine enhanced the GH response to GHRH in all subjects. The median GH peak after pyridostigmine + GH + GHRH was 32.7, range 19.8-42.1 micrograms/l (p less than 0.001 vs GHRH alone). Seven diabetic subjects had median GH peaks after GH + GHRH greater than 6.9 micrograms/l (the maximum GH peak after GH + GHRH in normal subjects) (group A: median GH peak 35.7, range 21.7-55 micrograms/l). The other diabetic subjects had GH peak lower than 6.9 micrograms/l (group B: median GH peak 4.4, range 2.1 6.5 micrograms/l). Pyridostigmine significantly increased the GH response to GHRH in group B patients (median GH peak 29.3, range 15.7-93.4 micrograms/l, p less than 0.001 vs GH + GHRH alone), but not in group A patients (median GH peak 39.9, range 21.9-64.9 micrograms/l). Group A diabetic patients were younger and had higher HbA1c and blood glucose levels than group B patients. In those diabetic patients with an exaggerated GH response to GH + GHRH, pyridostigmine failed to cause the increase in GH secretion observed in diabetic and control subjects with no responses to GH + GHRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759541 TI - Biosynthesis of 16-androstene steroids and testosterone by porcine testis tissue in vitro: effect of age and relationships with fat 5 alpha-androstenone levels in vivo. AB - The relationships between testicular 16-androstene and testosterone formation in young pigs and levels of 5 alpha-androstenone in fat exhibited at older ages were investigated. Testis tissue samples were taken from Large White male pigs at 75, 100 and 125 days of age (8 pigs per age group) and incubated with a mixture of [3H]progesterone and [14C]pregnenolone. 5 alpha-androstenone levels in fat were measured in all 24 pigs at 125, 145 and 170 days of age. Less androstadienone, more 3 alpha-androstenol and 11-fold more 3 beta-androstenol + androstadienol were synthesized from pregnenolone than from progesterone. 5 alpha-androstenone synthesis increased significantly between 100 and 125 days, whereas that of androstadienone declined between 75 and 100 days of age. Litter had a significant effect on all 16-androstene rates of formation. Fat 5 alpha-androstenone levels were positively correlated with 5 alpha-androstenone formation from both precursors. They were correlated with 3 beta-androstenol + androstadienol (positively) and testosterone (negatively) rates of synthesis from progesterone. It is concluded that in vitro measurements of 5 alpha-androstenone formation by testis tissue could be used as an early predictor of fat 5 alpha-androstenone levels exhibited at older ages. PMID- 1759542 TI - Balb/C mice immunized with either xenogeneic or syngeneic TSH produce immunoglobulins with anti-TSH and thyroid-stimulating activities. AB - Balb/C mice were immunized with bTSH (xenogeneic TSH) or extracts of Balb/C pituitaries (containing syngeneic TSH), either intracutaneously with Freund's adjuvant or intrasplenically. After bTSH, all blood samples contained anti-TSH antibodies. Thyroid-stimulating activity was assayed on FRTL-5 cells. Of 80 sera from immunized mice, 33 induced an increase in 99mTcO4 uptake, and 31/79 induced an increase in thyroidal 3[H]thymidine uptake by thyrocytes. With syngeneic TSH, anti-TSH antibodies were found in 10/19 mice. Immunoglobulins increasing thyrocyte technetium uptake were found in 14/19 mice, and immunoglobulins that stimulated thymidine uptake in thyrocyte DNA were detected in 12/19 sera. After immunization with both types of TSH, sera of some mice showed only one of the two bioactivities. Hybridomas were prepared with splenic lymphocytes of the mice immunized with either of the TSH preparations. These secreted TSH-binding immunoglobulins or immunoglobulins which stimulated thymidine or technetium uptake by the thyrocytes. One of the hybridomas from mice immunized with pituitary extract secreted a monoclonal antibody which stimulated thyroidal thymidine uptake, but inhibited bTSH-induced 99mTcO4 uptake. These findings might suggest that the anti-idiotypic network acting on TSH as an antigen could be involved in the pathogenesis of stimulatory antibodies in thyroid disease. PMID- 1759543 TI - Insulin-like growth factor II and transforming growth factor beta 1 regulate insulin-like growth factor I secretion in mouse bone cells. AB - Bone cells in culture produce and respond to growth factors, suggesting that local as well as systemic factors regulate bone volume. Previous studies have shown that IGF-I is the major mitogen produced by mouse bone cells and that its production is regulated by systemic agents such as PTH and estrogen. Because IGF II and transforming growth factor beta 1 have been shown, respectively, to increase and decrease MC3T3-E1 cell proliferation, we tested the hypothesis that these two growth factors modulate the production of IGF-I in this cell line. In order to eliminate artifacts owing to IGF binding proteins, conditioned media samples were pretreated with IGF-II before measurement of IGF-I by RIA. After 24 h treatment at a density of 2.5 x 10(4) cells/cm2, IGF-II (10 micrograms/l) induced a 2.2-fold increase compared with untreated control (9.5 +/- 1.5 vs 4.2 +/- 0.44 pg/micrograms protein, p less than 0.001), whereas transforming growth factor beta 1 (1 microgram/l) caused a 66% decrease in IGF-I production (1.5 +/- 0.3 vs 4.2 +/- 0.44 pg/micrograms protein, p less than 0.001). Both IGF-II and transforming growth factor beta 1 regulated IGF-I production in a dose-, time- and cell density-dependent manner. The lowest effective doses for IGF-II and transforming growth factor beta 1 were 1 and 0.01 microgram/l, respectively. These results support a role for IGF-II and transforming growth factor beta 1 as potent modulators of IGF-I secretion in mouse bone cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759544 TI - Comparative effects of chronic administration of the non-steroidal antiandrogens flutamide and Casodex on the reproductive system of the adult male rat. AB - The effects of chronic blockade of androgen action by the antiandrogens flutamide and Casodex on serum and pituitary concentrations of LH and FSH, serum and testicular androgen levels, reproductive organ weights, and on spermatogenesis were compared in the adult rat. Animals were treated for 3 and 8 weeks with vehicle, Casodex (20 mg.kg-1.(day)-1, flutamide (20 mg.kg-1.(day)-1) and GnRH antagonist (150 micrograms/day, Detirelix). Treatment with GnRH antagonist suppressed gonadotropin and testosterone production, reduced the weights of testes, epididymides and seminal vesicles, and inhibited germ cell development. Flutamide administration markedly elevated serum and pituitary levels of gonadotropins as well as serum and testicular androgen concentrations. Casodex induced elevation of gonadotropin concentrations was less pronounced and serum and testicular levels of androgens did not change significantly. The reduction of seminal vesicle weights was similar after Casodex and GnRH antagonist treatment, whereas flutamide was less effective. Testicular weight and spermatogenesis (assessed by light microscopical and flow-cytometric analysis) remained unaffected by Casodex and flutamide. It is concluded, that 1. Casodex, in contrast to flutamide, is a peripherally selective antiandrogen, and 2. Casodex influences release of gonadotropins into circulation less than flutamide. Therefore this antiandrogen might be useful clinically for selectively blocking androgen actions in the accessory sex glands. PMID- 1759545 TI - Dehydration, but not vasopressin infusion, enhances the adrenocortical responses of sheep to corticotropin-releasing hormone or restraint. AB - Two experiments were carried out using adult castrated sheep prepared with jugular vein catheters. In Experiment 1, sheep (N = 8) were injected iv with saline vehicle, vehicle + 15 or 30 micrograms oCRH, or subjected to 120 min mild physical stress (restraint), following a 48 h period during which water was freely available or withheld. Blood samples were taken for 30 min before and 120 min after oCRH injection, and before and during restraint, and the plasma analysed for AVP and cortisol content. Levels of AVP increased by over 500% after dehydration, but were unaffected by oCRH or restraint. In contrast, plasma cortisol was unchanged after dehydration, but increased after oCRH and restraint. Moreover, these cortisol responses were significantly greater when the sheep were dehydrated. In Experiment 2, euhydrated sheep (N = 6) were infused iv with saline vehicle or vehicle + AVP for a 5-h pretreatment period, followed by a 2-h experimental period in which the animals were injected with 15 micrograms oCRH or subjected to 120 min restraint, as in Experiment 1. Blood samples were taken throughout the experiment from a contralateral catheter and the plasma analysed for AVP and cortisol content. The AVP infusion produced plasma levels of the hormone approximately twice those seen after 48 h dehydration in Experiment 1, but did not affect cortisol secretion. Furthermore, the cortisol response to oCRH, or restraint, was not enhanced by the AVP infusion. These results suggest that pituitary responsiveness to exogenous or endogenous CRH (restraint stress) may be enhanced in sheep by dehydration through a mechanism that does not involve an adrenal or pituitary action of circulating AVP. PMID- 1759546 TI - Expression of GH receptor mRNA in regenerating skeletal muscle of normal and hypophysectomized rats. An in situ hybridization study. AB - Expression of growth hormone receptor mRNA was investigated by in situ hybridization in skeletal muscle from normal and hypophysectomized rats during the first seven days of regeneration after ischemic injury. A digoxigenin labelled RNA probe directed against the extracellular part of the rat GH receptor was used. In both normal and hypophysectomized rats distinct expression of GH receptor mRNA could be demonstrated in the regenerating muscle cells at the myoblast/myotube stage. The GH receptor expression appeared to decline with increasing maturation of the regenerated muscle fibres. In hypophysectomized rats, the regeneration process and the expression of GH receptor mRNA was delayed compared with that in normal animals. It is concluded that growth hormone may affect also the early phase of muscle regeneration in normal animals. To what extent lack of growth hormone contributes to the delayed regeneration observed in the hypophysectomized rats remains to be elucidated. PMID- 1759547 TI - Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: stimulation of the inositol phosphate second messenger system. AB - Thyroid hormones increase cytosolic free calcium by binding to plasma membrane receptors in several tissues. This calcium increase appears to initiate extranuclear effects in these tissues. Increases in cytosolic calcium are often a consequence of stimulation of inositol phosphate second messenger pathway. Several calcemic hormones act via this signal transduction route. Therefore we investigated the effects of the metabolically active T3 and the inactive analogues 3,5-diiodotyrosine and rT3 on the inositol phosphate pathway in fetal rat limb bone cultures prelabeled with [3H]myoinositol. Labelled inositol and inositol phosphates were separated by HPLC. There was a significant increase in the radioactivity in inositol bis- and trisphosphates after 1 min of exposure to 10(-7) mol/l T3. Stimulation was also observed at 10(-6) mol/l T3, but not at 10( 5) mol/l. Time course studies demonstrated a rapid effect of T3 on inositol phosphates within 30 seconds that lasted through 5 min. After 20 min incubation with T3, no increase was observed in inositol mono- and bisphosphates, and a decrease was seen in inositol trisphosphate. Pretreatment with indomethacin prevented these effects of T3. 3,5-diiodotyrosine and rT3 did not affect inositol phosphate metabolism. These results suggest the existence of plasma membrane associated receptors for T3 in bone, in addition to the nuclear receptors demonstrated previously. The role of these receptors in the effects of thyroid hormones on bone remains to be established. PMID- 1759548 TI - A twin study approach towards understanding genetic contributions to body size and metabolic rate. AB - The genetic and environmental determinants of a brief assessment of metabolic rate at rest and under psychological stress were studied in 40 pairs of monozygotic and 40 pairs of dizygotic young adult male twins. Height, weight and age were employed as covariates. Univariate analyses showed a high heritability for height and weight and moderate heritability for metabolic rate. Classical twin analyses and multivariate genetic modeling indicated that genetic influences on resting metabolic rate were entirely explained by body weight: there was no independent genetic contribution to resting metabolic rate. Metabolic rate under psychological stress, on the other hand, showed a significant genetic effect. The exponent (3/4) in the power function relating body weight to resting metabolic rate was the same as that found in a wide variety of animal species, a value that has been proposed as defining a body weight set point. We speculate that an adult body weight set point is genetically transmitted. Independent genetic effects on resting metabolic rate would be observed only when the normal equilibrium between body weight and metabolic rate is unbalanced during development, aging or disease. The study illustrates the use of multivariate genetic analyses of twin data which may be readily applied to widely used metabolic rate assessments. PMID- 1759549 TI - Zygosity, placental membranes and Weinberg's rule in a Danish consecutive twin series. AB - The usual assumption that monochorionic twins are monozygotic has recently been questioned, based on blood group discordance in 3 of 12 monochorionic pairs. Therefore, this study evaluates the validity of zygosity diagnosis based on examination of placental membranes, and at the same time evaluates Weinberg's differential rule in a Danish consecutive twin series. All twin pairs, 265 like sexed and 87 unlike-sexed pairs, born at Odense University Hospital, Denmark, from 1 January 1980 through 31 August 1988, were ascertained. In 229 like-sexed pairs, zygosity was determined by serological methods, and in 190 of these, the fetal membranes could be reliably classified. Fifty-nine monochorionic twin pairs were identified and none of those pairs were discordant for any genetic markers. Therefore, we conclude that monochorionic twins can be considered monozygotic. The distribution of monozygotic and dizygotic pairs was in accordance with Weinberg's rule. PMID- 1759550 TI - Northwestern University Twin Study X: Outcome of twin gestations complicated by gestational diabetes mellitus. AB - Existing data concerning the effect of gestational diabetes on perinatal outcome in twin pregnancies is scant. We hypothesized that altered carbohydrate metabolism would worsen perinatal outcome in twin gestation in a manner similar to singleton gestation. Thirteen twin pregnancies complicated by gestational diabetes mellitus were matched by gestational age at delivery to 13 twin pregnancies unaffected by gestational diabetes. Comparing infants of diabetic mothers to infants of control mothers, there was a trend of greater likelihood of respiratory distress syndrome, hyperbilirubinemia, and prolonged neonatal intensive care nursery admissions. Our experience suggests that altered carbohydrate metabolism in multiple gestations increases the potential for neonatal morbidity. PMID- 1759551 TI - Efficient sequential search of genetic systems for diagnosis of twin zygosity. AB - Conventionally, the zygosity of twins into monozygotic (MZ) and dizygotic (DZ) is determined by utilizing several blood groups or other genetic markers. Existence of many blood groups or other genetic markers raises the crucial problem of choosing minimum number of blood groups and applying them in a sequence with minimum cost offering maximum effectiveness in classifying the twins by zygosity. In this note, a statistical approach to this problem is made and a solution provided. The efficient sequential search procedure utilizing the gene frequency of four blood groups from the German population of Nordrhein-Westfalen province and applying the results to a twin set of 72 pairs (32 MZ and 40 DZ) of the same population indicates that efficient sequences with 3 and 4 blood groups are AB0-- -P----Rh and AB0----P----Rh----MNSs, respectively. Further, it is understood that the efficient sequence for zygosity determination will be differing from population to population. As gene frequencies of blood systems differ in the various populations, this will effect the probability that a DZ twin pairs is concordant for a specific marker. Moreover, the relative cost may also turn out to be a decisive factor in the determination of the best sequence. Hence, indiscriminate use of several conventional blood group systems in the determination of zygosity of twins from a particular population should be discontinued. The formulae developed in this note are quite general and the procedure explained can easily be generalized to other situations. PMID- 1759552 TI - Iatrogenic influences on the heritability of childhood tonsillectomy: cohort differences in twin concordance. AB - In 1980-82, a mailed questionnaire was completed by 3,810 pairs of adult twins enrolled on the Australian NH&MRC Twin Register. Twins were asked whether they had had their tonsils out and, if so, at what age. The sample was divided into four birth cohorts of approximately equal size, and only childhood tonsillectomy (to the age of 18) was considered. The prevalence of tonsillectomy differed markedly between cohorts, being highest in those born in the 1940s and early 1950s. Within each cohort, the prevalence was very similar in MZ and DZ twins, yet concordance was much higher in MZ twins, indicating the importance of genetic factors in predisposition to tonsillectomy. However, the proportions of variance in liability due to genetic and shared environmental factors differed markedly between cohorts. In the 1950s, when tonsillectomy was fashionable, shared environment accounted for 60% of variance and genetic factors for only 29%. However, by the early 1960s, when tonsillectomy was going out of fashion, heritability was up to 0.82 and shared environment accounted for only 10% of variance. Our results illustrate, once again, that heritability is not a constant, but depends on the precise characteristics of the population and the time at which it is studied. PMID- 1759553 TI - Influence of clinical variables on triplet birth weight. AB - The small size of most reported triplet series has resulted in conflicting statements about the influence of several clinical variables on triplet birth weight. Therefore, obstetrical and neonatal data were collected on 196 mothers and their 580 infants (8 stillbirths excluded). Gestational age was based on the date of fertilization in 13 IVF triplets and on the date of ovulation in 90 medically induced triplets. Obstetrical and ultrasonic criteria were used to estimate the date of confinement in 93 spontaneous triplets. Birth weight appeared to be higher in males and with higher maternal parity, independent of gestational age. The apparent effect of medical technologies such as ovulation induction or IVF on combined triplet birth weight disappeared when maternal parity and fetal gender were controlled. Preeclampsia, maternal race and zygosity were not significantly associated with birth weight. While birth order did not significantly effect ultimate birth weight, the heaviest triplet did present first more often than would be expected by chance alone. Future evaluation of neonatal outcome data in multifetal gestations should control for gestational age, fetal gender and maternal parity. It appears that triplet birth weight is not affected by etiology, which is important given the significant impact of medical technologies. PMID- 1759554 TI - Time trends in characteristics and outcome of twin pregnancies. AB - This study describes the evolution in fetal and neonatal mortality rates among twin pairs born in 22 hospitals located in the eastern regions of the province of Quebec in 1976-1978 (n = 776 pairs) and 1982-1985 (n = 712 pairs). It also assesses the contribution of maternal factors, obstetrical care and characteristics of twins in the variation of the risk of death over time. The fetal mortality rate did not improve from 1976-1978 (22.6 per 1000) to 1982-1985 (28.1 per 1000). However, the neonatal mortality rate declined from 44.7 to 34.7 per 1000 liveborn first twins and from 56.8 to 36.1 per 1000 liveborn second twins. For first twins as for second twins, birthweight-specific neonatal mortality rates decreased within birthweight categories under 2500 g. In the second period, 96.9% of twin pregnancies were detected before confinement compared to 59.6% in the earlier period. The proportion of twins delivered by obstetricians, the percentage of twin births occurring in ultraspecialized perinatal units and the frequency of caesarean sections increased markedly. The proportion of preterm births increased over time (34.5% vs 43.1%) whereas the percentage of low birthweight twins decreased but not significantly (54.3% 51.6%). In this study, changes in maternal age, parity, educational level, sex of pairs, qualification of the physician, and level of care available at the hospital of birth, did not account for the decrease in neonatal mortality rates among twins. The increase in the frequency of caesarean sections seemed to explain only a small proportion of the decrease in the neonatal mortality rate among second twins. In the second as well as in the first period, the neonatal mortality rate for twins was six times higher than that for singletons. PMID- 1759555 TI - Factors associated with neonatal problems in twin gestations. AB - We examined the neonatal outcome of 644 twins weighing 500 g or more and 656 singletons, born in the years 1984-1986 in the Soroka Medical Center, Beer-Sheva, Israel. There was nearly a four-fold risk of antepartum death in twins vs singletons, which disappeared when birth weight was controlled for. The risks for intrapartum and early neonatal mortality were not raised in this population. A statistically significant relative risk for congenital heart malformations in twins vs singletons remained (RR = 5.0, 95% CI = 1.5-16.3), after controlling for maternal age. Significantly higher rates of hyalin membrane disease, hypoglycemia, hyperbilirubinemia, anemia and septicemia were found in twins. Controlling for the confounding of the association between twinning and mortality or morbidity caused by differences in distributions of mode of delivery or gestational age between twins and singletons, was not as efficient as the controlling for birth weight. Thus, adjustment for birth weight removed all the excess risks detected except in hypoglycemia. Our findings suggest that the lower birth weight of twins, which is so intimately associated with multiple gestations, is probably the single most important factor associated with neonatal problems found in twin births. PMID- 1759557 TI - [Abstracts of the 96th Meeting of the Japanese Association of Anatomists. Kyoto, April 2-4, 1991]. PMID- 1759556 TI - [Osteoclasts in bone metabolism]. AB - Bone resorption plays an important role in bone modeling and remodeling. Osteoclasts are the cells responsible for the bone resorption. Osteoclasts are located on endosteal bone surfaces and on the periosteal surface beneath the periosteum. They are multinucleated giant cells highly polarized in their morphology and function. Among the proximal surface, the membrane and the area of the cytoplasm directly oppose to the bone surface, which are specialized into two regions. A central region consisting of many irregular cytoplasmic processes and infoldings, the ruffled border, is known to be the active site of bone resorption. Surrounding the ruffled border, a second region, the clear zone provides an area of close attachment to the mineralized bone surface. The osteoclasts secrete a large amount of protons by the action of H(+)-pump on the ruffled border into the sealed resorption cavity, resulting in the acidified microenvironment under which condition the bone matrix is dissolved. Protons are provided by the intracellular action of carbonic anhydrase. Following the secretion of the protons, several ion-transporting systems, i.e., carbonate chloride exchanger, chloride-channel, Ca(2+)-transport systems, Na+/K(+)-ATPase, and voltage-dependent Ca(2+)-channel, are sequentially operated on both apical and basolateral cytoplasmic membranes. In addition, osteoclasts contain a large amount of lysosomal enzymes (cathepsin C, beta-glycerophosphatase, beta glucuronidase, etc.), which contribute to degrade the bone organic matrices exposed in the resorption cavity. These enzymes bind to the mannose-6-phosphate receptor on Golgi apparatus, are transported to the ruffled border and are secreted into the extracellular compartment in an exocytotic manner. Osteoclasts also have a high tartrate-resistant acid phosphatase activity which is currently used as a marker enzyme osteoclastic differentiation. Osteoclasts are considered to develop from hematopoietic stem cells. So far, the following four different pathways of the differentiation of osteoclast are proposed: The precursors of osteoclast develop (1) from multilineage hematopoietic cells via a completely separate differentiation line, (2) from granulocyte macrophage-colony forming cells, (3) from committed but proliferative monocyte-macrophage, and (4) from mature and unproliferative monocyte-macrophage. However, the differentiation line of the osteoclasts has still to be elucidated. The formation of osteoclasts as well as that of other hematopoietic cells is strongly regulated by many cytokines [interleukin (IL)-1,IL-3,IL-6, M-colony stimulating factor (CSF), and GM-CSF]. 1,25-Dihydroxyvitamin D3 and parathyroid hormone also stimulate the differentiation of osteoclast precursors. However, the mature osteoclasts do not possess the receptors for these hormones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1759558 TI - Neuropathological stageing of Alzheimer-related changes. AB - Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations. PMID- 1759559 TI - Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats. AB - After 180 min of temporary middle cerebral artery occlusion in rats, the affect of phenylephrine-induced hypertension on blood-brain barrier permeability was assessed. One of the following blood-pressure regimens was maintained during either a 30- or 120-min period of reperfusion: (a) 30/Norm, 30 min of normotensive reperfusion was allowed; (b) 30/HTN, mean arterial blood pressure was increased by 35 mm Hg during 30 min of reperfusion; (c) 120/Norm, 120 min of normotensive reperfusion was allowed; or (d) 120/HTN, mean arterial blood pressure was increased by 35 mm Hg during 120 min of reperfusion. Evans blue (30 mg/kg) was given, and brains were analyzed for Evans blue by spectrophotometry. Evans blue (microgram/g brain tissue, mean +/- SD) was greater (P less than 0.05) in both hypertensive groups versus their time matched normotensive groups (30/HTN: 80 +/- 16 versus 18 +/- 6 in the 30/Norm group; 120/HTN: 17 +/- 6 versus 8 +/- 3 in the 120/Norm group). In addition, Evans blue was greater (P less than 0.05) in both 30-min groups versus their pressure matched 120-min groups (30/Norm: 18 +/- 6 versus 8 +/- 3 in the 120/Norm group; 30/HTN: 80 +/- 16 versus 17 +/- 6 in the 120/HTN group). The data are consistent with previous studies which have demonstrated an opening of the blood-brain barrier at the onset of reperfusion. In addition, the data support a hypothesis that changes in blood brain barrier permeability are more sensitive to hypertension in the early period of reperfusion. PMID- 1759560 TI - Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. AB - A histopathological study was carried out on the brains of eight ex-boxers (ages 56 to 83) using conventional histological staining methods and immunocytochemistry with antibodies to amyloid beta-protein and the PHF-related tau protein. All cases showed a large number of tau-immunoreactive neurofibrillary tangles and also beta-protein immunoreactive senile plaques in the cortex. In the areas with many neurofibrillary tangles, neuropil threads with tau-immunoreactivity were also observed, and some of the senile plaque lesions were surrounded by abnormal neurites with tau-immunoreactivity. Moreover, three cases revealed beta-protein-type cerebrovascular amyloid deposits on both leptomeningeal and cortical blood vessels. The present observations indicate that the cerebral pathology of dementia pugilistica is very similar to that of Alzheimer's disease and suggest that these two disorders share some common etiological and pathogenic mechanisms. PMID- 1759561 TI - Calcitonin gene-related peptide immunoreactivity in spinal spheroids in motor neuron disease. AB - The spinal cords from seven autopsy cases of sporadic motor neuron disease (MND) and two controls were immunohistochemically examined using antibodies directed to calcitonin gene-related peptide (CGRP) and to neurofilament proteins (Nf). CGRP immunoreactivity was observed in the posterior horns, especially in the laminae I and II, of all the spinal cords examined. In MND cases, in addition, a considerable number of spheroids in the anterior horns were labelled with the antibody. In some spheroids, their entire area was homogeneously immunostained, whereas in others the immunoreactivity was confined to a focal area(s) within the profile of the spheroids and between these two forms of staining several variations of the staining patterns were seen. The anti-Nf intensely and homogeneously labelled all spheroids and there was no appreciable difference in the Nf-immunoreactive pattern between CGRP-positive and -negative spheroids. It is possible that the accumulation of CGRP in spheroids may result from entrapment of CGRP during the anterograde axonal transport, causing loss of CGRP at the neuromuscular junction and producing weakness and atrophy of the muscles. PMID- 1759562 TI - Senile dementia of the Alzheimer type: is there a correlation between entorhinal cortex and dentate gyrus lesions? AB - Senile plaques (SP) are one of the neuropathological hallmarks of senile dementia of the Alzheimer type (SDAT). In 14 patients affected with SDAT (over 74 years of age), thioflavine S, Tau and acetylcholinesterase (AChE) stainings demonstrated an increased density of SP in the outer two thirds of the dentate gyrus molecular layer. However, a wide range of SP density was observed among the cases. The molecular layer of the dentate gyrus is one of the termination site of the perforant pathway that originates in layers II and III of the entorhinal cortex. We have found that the number of AChE-, thioflavine S- and Tau-positive SP that accumulate in the dentate gyrus is positively correlated with the density of thioflavine S-stained neurofibrillary tangles in layers II and III of the entorhinal cortex. In contrast, a similar correlation is not found when using Tau immunolabeling of the entorhinal tangles. These observations show an association between the accumulation of AChE-positive SP in the dentate molecular layer and the lesions of the perforant pathway. Furthermore, they suggest that the density of SP in the dentate gyrus correlates with the late stages of neurofibrillary tangles formation (thioflavine S positive), but not with the early stages (Tau positive). PMID- 1759563 TI - Neuropathological observations in a case of autism presenting with self-injury behavior. AB - We report the neuropathological evaluation of a 24-year-old autistic woman suffering from a residual state of infantile autism and presenting with self injury behavior since childhood. Her behavior included head-banging, eye-gouging and self-biting. All intended therapeutic measures remained without effect, including high doses of psychotropic drugs. At autopsy, numerous neurofibrillary tangles were found in the perirhinal and entorhinal cortex where they were frequently grouped in nests or clusters. A few neurofibrillary tangles were also observed in the amygdala and in the prepiriform and orbito-frontal cortex. In the cortex, tangles were located in both layers II and III. There were no neuritic plaques or amyloid deposits. Interestingly, neurofibrillary tangles have been described in brains of individuals who had experienced repeated head injuries such as boxers (dementia pugilistica) and soccer players, suggesting that in our case a similar mechanism induced tangle formation and resulted in the loss of selective neuronal populations. PMID- 1759564 TI - Effect of electric stimulation on vestibular compensation in guinea pigs. AB - The effect of electric stimulation on vestibular compensation was studied in guinea pigs. Pharmacological labyrinthectomy was performed by injecting chloroform into the right middle ear under light ether anesthesia. The guinea pigs were divided into four groups: a control group which was not electrically stimulated after labyrinthectomy, a group stimulated with 0.6 mA square wave, a group stimulated with 0.3 mA square wave, and a group stimulated with 0.6 mA pulse wave. Electric stimulation, which started 1 h and 15 min after labyrinthectomy, was given through retroauricular electrodes. Nystagmus and head deviations were recorded and analyzed to assess the process of compensation at 1, 2, 3, 4, 5, 8, 12, 18 and 24 h after labyrinthectomy. Electrically stimulated groups, especially group 0.6 mA square wave and group 0.6 mA pulse wave, showed faster compensation in nystagmus and head-body deviation than the control group. Therefore, in this study, electric stimulation seemed to contribute favorably to vestibular compensation. PMID- 1759565 TI - Visual influence on postural reactions to sudden antero-posterior support surface movements. AB - Visual influence on force reactions to sudden antero-posterior (AP) translations of the support surface in 10 healthy men 23-58 years old (mean 36 years) were studied. Displacements ranged between 13 and 127 mm in both backwards and forwards directions. The experiment was conducted using a modified EquiTest dynamic posturography apparatus. An interactive menu-driven software enabled selection of a suitable translation pattern (i.e. square wave) in the AP direction. Data from four vertical force transducers were acquired and the position of centre of pressure (CP) in the AP direction was computed as function of time. The movement of CP in response to AP translation was characterized by the amplitude of the maximum CP displacement relative to the platform and the latency until maximum CP displacement occurred. The experiment unveiled that the latency to maximum CP displacement was larger for conditions with vision present. Furthermore, both the amplitude and latency to maximum CP deflection were increasing functions of translation amplitude. It is proposed that visual feedback influences the neural control on the postural reactions to sudden support surface translations. Absence of visual cues seems to cause a more rapid correction of the body position. PMID- 1759566 TI - Effects of hydrostatic pressure on sensory discharge in frog semicircular canals. AB - The effects of endolymphatic and perilymphatic pressure changes on resting and mechanically evoked responses were studied in isolated posterior semicircular canals of the frog. The results demonstrated that ampullar receptors are extremely sensitive to hydrostatic pressure changes (0.25 mm H2O were sufficient to produce distinct changes), being inhibited by endolymphatic pressure increases and facilitated by perilymphatic ones. Intracellular recordings from single afferent axons showed that the effects of hydrostatic pressure result from a modified transmitter release from the synaptic pole of the hair cells. Unlike resting activity, mechanically evoked activity was always depressed in the presence of a hydrostatic pressure. This indicates that the sensitivity of ampullar receptors to mechanical stimuli, i.e. the gain of the conversion process, is maximal when no pressure is present between the inner and the outer fluid. The possible action of hydrostatic pressure on vestibular receptors is discussed. PMID- 1759567 TI - Age-related loss of auditory sensitivity in two mouse genotypes. AB - Frequency-specific auditory brainstem responses (ABR) (frequency range 2-31.5 kHz) were used to describe age-dependent alterations in frequency sensitivity in CBA/ca (to 30 months) and C57BL/6J (to 16 months) mouse genotypes. The two strains displayed an age-related loss similar to that of humans, with a primary decline in high-frequency sensitivity. CBA mice showed a slow, yet gradual decrease in sensitivity to high- followed by low-frequency until 18 months of age and a rapid deterioration at all frequencies thereafter. C57 mice demonstrated precocious aging in auditory sensitivity in an unsteady rather than gradual manner. By testing the same individuals on repeated occasions it was shown that, for C57 mice, the degenerative process was more precipitous with three phases, and that the individual variability was larger than that of CBA mice. It is suggested that the two mouse genotypes can be used to express the different aspects of human presbycusis in individual variability and modes of gradual or staggered progression. PMID- 1759568 TI - Spontaneous otoacoustic emissions and sensori-neural hearing loss. AB - This study sought to clarify the clinical relevance of spontaneous otoacoustic emissions (SOAEs) and to define the hearing loss level (and frequency) at which absence of SOAE is found. Findings from 126 ears of patients with sensori-neural hearing loss showed an incidence of SOAEs in 18.25% of the cases (23 out of 126 ears). SOAEs were never found when hearing loss at 1,000 Hz exceeded 10 dB. The presence of SOAE seems to indicate a good cochlear functioning at least in the mid-frequencies. Although the incidence of SOAEs is markedly lower than that of evoked otoacoustic emissions (EOAEs), SOAE recording is shown to be a good test, rapid, non-invasive for audiological screening, the presence of SOAE confirming a hearing threshold of less than 10 dB at 1,000 Hz, the absence of SOAE being inconclusive. PMID- 1759569 TI - Hypothermia differentially affects tuning curves generated by forward and by simultaneous masking. AB - In the gerbil maintained at euthermic (37.5 degrees C) conditions, forward masking produces a compound action potential tuning curve (CAP TC) which is less sensitive but more sharply tuned than that which is generated by simultaneous masking. These differences between forward- and simultaneously-masked CAP TCs are minimized at hypothermic (30 degrees C) conditions. The unmasking effect occurs at both temperatures, suggesting that hypothermia does not exert these changes by eliminating two-tone suppression. PMID- 1759570 TI - Cochlear pathology following chronic electrical stimulation using non charge balanced stimuli. AB - During the course of a chronic intracochlear electrical stimulation study using charge balanced biphasic current pulses, one animal inadvertently received a short period of direct current (DC) stimulation at a level of approximately 1 microA. Subsequent, the animal was chronically stimulated using a poorly charge balanced waveform that produced a DC level of approximately 2 microA. Extensive pathological changes were observed within the cochlea. These changes included widespread spiral ganglion cell loss and new bone growth that extended throughout all turns of the cochlea. Significant changes in the morphology of the electrically evoked auditory brainstem response (EABR) were associated with these pathological changes. EABRs recorded prior to the DC stimulation exhibited a normal waveform morphology. However, responses recorded during the course of the DC stimulation were dominated by a short latency response believed to be vestibular in origin. The response thresholds were also significantly higher than levels recorded before the DC stimulation. In contrast, the contralateral cochlea, stimulated using charge balanced stimuli, showed no evidence of adverse pathological changes. Furthermore, EABRs evoked from this cochlea remained stable throughout the chronic stimulation period. Although preliminary, the present results illustrate the adverse nature of poorly charge balanced electrical stimuli. These results have important implications for both the design of neural prostheses and the use of DC stimuli to suppress tinnitus in patients. PMID- 1759571 TI - Left-right asymmetry in the human response to experimental noise exposure. II. Pre-exposure hearing threshold and temporary threshold shift at 4 kHz frequency. AB - The repeatedly noted average inferiority of the left ear (or superiority of the right ear) in epidemiological surveys at frequencies most susceptible to noise damage has not been experimentally confirmed. Twenty-eight non-shooting young adults were exposed binaurally to broad-band noise for a maximum of 8 h in strictly symmetrical laboratory conditions. The left and right hearing thresholds of each individual were monitored during short interruptions in the exposure. The average interaural hearing threshold difference became statistically significant during the exposure, the left ear being worse than right. The negative correlation found between the pre-exposure threshold level and the temporary threshold shift (TTS) was more marked in the left than in the right ear. In conclusion a hypothesis is presented: a good hearing threshold level in the right ear seems to be better protected from noise-induced temporary threshold shift than a good hearing threshold in the left ear. PMID- 1759572 TI - Chronological study of recovery of sudden deafness treated with defibrinogenation and steroid therapies. AB - The time courses of hearing recovery resulting from two types of treatment of sudden deafness patients, defibrinogenation (DF) therapy and betamethazone (BM) therapy, were analyzed and compared. A paired double-blind comparative study was performed on 168 patients. The average hearing level was 79.2 dBHL in the DF therapy group (n = 82) and 82.3 dBHL in the BM therapy group (n = 86). The DF group showed significantly better hearing 1 week after start of treatment at frequencies of 0.25, 0.5 and 1 kHz. After 2 weeks of treatment, the average hearing level for the frequency range of 0.25-4 kHz was 47.0 dBHL with DF therapy and 55.8 dBHL with BM therapy. Thus, the DF group still showed better hearing than the BM group (p less than 0.10, t-test), but not as significantly as after 1 week. It is concluded that therapy for increasing blood circulation is important in the early phase of sudden deafness, especially for hearing loss in the low to middle frequency range. PMID- 1759573 TI - Transport of HRP through Reissner's membrane in experimental endolymphatic hydrops. AB - Unilateral endolymphatic hydrops was produced in guinea pigs by cauterization of the endolymphatic sac. Measurements of compound action potential (CAP), cochlear microphonics (CM) and negative summating potential (-SP) confirmed endolymphatic hydrops three months after surgery. In both control and hydropic ears, reaction product of HRP was observed only on the perilymphatic surface of the epithelial cells of Reissner's membrane after 10 min perfusion, while it was observed on both the endolymphatic and perilymphatic surfaces after 30 min perfusion. Epithelial tight junctions were not stained and labelled pinocytotic vesicles were observed in the epithelial cells. These findings suggest that the transport of HRP through Reissner's membrane is unchanged in endolymphatic hydrops and that the epithelial junctions are tight regardless of the distension of Reissner's membrane. PMID- 1759574 TI - Isolation of and calcium kinetics in cochlear inner hair cells of the guinea pig. AB - Single inner hair cells of the guinea pig cochlea were isolated using enzymatic and mechanical techniques. The intracellular free calcium ion concentrations [( Ca2+]i) of the isolated inner hair cells were determined using the Ca2+ sensitive dye fura-2 and digital imaging microscopy. In the presence of 1 micron ionomycin, a Ca2+ ionophore, there was an irreversible increase in [Ca2+]i. The 150 mM KCl stimulation, which induces a depolarization, resulted in a temporary increase in [Ca2+]i. This increase in [Ca2+]i was not observed under conditions of depolarization, in Ca(2+)-free medium. These observations are interpreted to mean that the [Ca2+]i during membrane depolarization mainly originates from an influx of extracellular Ca2+ into the cytoplasm. PMID- 1759575 TI - Degeneration of the organ of Corti following intravenous administration of cisplatin. AB - The development of acute morphological changes in the cochlea was studied in guinea pigs given one intravenous high-dose injection of cisplatin. In the light microscope three major stages of degeneration in the organ of Corti could be recognized: 1) an initial swelling of the Hensen's cells and protrusion of the Deiters' cells into the space of Nuel enclosing the outer hair cells, 2) a gradual degeneration of the outer hair cells together with a vacuolization in the region of the base of the inner hair cells, 3) a collapse of the Reissner's membrane and the entire organ of Corti with different degrees of damage to the inner hair cells. Sporadic bulging of the marginal cells of the stria vascularis into the endolymphatic space could be observed 4 days after injection. PMID- 1759576 TI - Evaluation of procedures to reduce fluid flow in the fistulized guinea-pig cochlea. AB - The rate of longitudinal flow of fluid in scala tympani (ST) has been quantified under a number of experimental conditions. The method used to measure flow involved using a tracer ion (trimethylphenylammonium: TMPA) as a volume flow marker. Movement of marked perilymph was monitored by ion-selective microelectrodes which were capable of detecting exceedingly low concentrations of TMPA. Our results show that when the cochlea is perforated at the apex, flow rates of 400-500 nl/min are induced in ST, compared to the normal very slow rate of 2 nl/min when the cochlea is sealed. This artifactual flow of CSF through the perforated cochlea can be reduced to 6.9 nl/min by releasing the hydrostatic pressure of cerebrospinal fluid (CSF) or further reduced to 1.8 nl/min by surgically obstructing the cochlear aqueduct. In addition, we observed no basally directed flow in ST when the round window (RW) was perforated, demonstrating that perilymph is not produced in volume as previously assumed. This study demonstrates the importance of separating artifactual flows, induced by the experimental procedures required to access the cochlear fluids, from the low flow rates which occur in normal, physiologic conditions. PMID- 1759577 TI - Feasibility of pulse oxymetry to measure arterial O2 saturation in studies on cochlear blood circulation. AB - To understand the characteristics of oxygen transport to the inner ear, the relationship between arterial O2 saturation and cochlear microcirculation was investigated under different respiratory condition in guinea pigs. To monitor arterial O2 saturation a pulse oxymeter instead of an arterial blood gas analyzer was used. When the arterial O2 saturation was measured in the foot pad by a pulse oxymeter under different respiratory conditions, the data showed a close correlation with the results of blood gas analysis. For the measurement of cochlear microcirculation, a pulse oxymeter was found to be a feasible respiratory monitor for animal experiments. With this apparatus our study demonstrated a slower reaction in the decrease of perilymphatic oxygen tension than of cochlear blood flow during stepwise induction of hypoventilation monitored by a pulse oxymeter. Under certain conditions of hyperventilation in which arterial O2 saturation and perilymphatic oxygen tension increased gradually, cochlear blood flow was found to decrease. This decrease of cochlear blood flow could be attributed to chemical controls which are regulated, as in the cerebral blood circulation, by the content of CO2 and H+ in the vascular bed in the cochlea. PMID- 1759578 TI - Computer-aided three-dimensional reconstruction of guinea pig cochlear aqueduct. AB - A computer-aided method of three-dimensional reconstruction was applied to the determination of the overall spatial configuration of the guinea pig cochlear aqueduct. The rotation function of the reconstructed images was useful in showing the individual small parts of the duct. A semi-translucent display of the segmental reconstruction of the duct demonstrated a difference in the density of the cellular components between the opening to the perilymphatic space and the duct portion. We propose that the cochlear aqueduct serves as a protective mechanism against a sudden change in CSF pressure in the subarachnoid space. PMID- 1759579 TI - The effect of acetazolamide on the endolymphatic sac DC potential. AB - The effect of acetazolamide known as a potent carbonic anhydrase inhibitor of the endolymphatic sac DC potential (ESP) was examined in the guinea pig. Intravenous administration of acetazolamide produced a dose-dependent decrease in ESP amplitude at doses of less than 10 mg/kg. The effect of acetazolamide on ESP was saturated at doses exceeding 10 mg/kg. The maximum reduction of ESP induced by acetazolamide was approximately 50% of the original ESP amplitude. The results suggest that carbonic anhydrase is involved in the generation of ESP. PMID- 1759580 TI - Polyp formation by experimental tubal occlusion in the rat. AB - The purpose of this study was to show the early stages of polyp formation, as part of our studies on the pathogenesis of nasal polyps. Two and 4 weeks after experimental tubal occlusion in 18 Wistar rats, 13 showed signs of bacterial infection, respective acute otitis media. In the majority of these rats polypouslike protrusions of the middle ear mucosa were found in whole-mount specimens. All polypouslike protrusions were investigated by cross sections, which revealed localised accumulation of fluid and inflammatory cells in the lamina propria. The polyps were covered with a flattened epithelium, compared to the epithelium in the surroundings. In some of the bigger polyps the apical part was without epithelial covering. The findings suggest that the epithelium by fast polyp growth may be distended and may burst, or that a primary epithelial defect has not been sufficiently covered. PMID- 1759581 TI - Neurophysiology of ischemic facial nerve paralysis in an animal model. AB - The establishment of an animal model for facial nerve paralysis is assuming increasing importance in clinical medicine and also in basic facial nerve research. We previously reported an animal model for ischemic facial nerve paralysis using selective vascular embolization through the internal maxillary and posterior auricular arteries in cats using Avitene which contains bovine microfibril collagen. In this paper, we determined the exact site of the lesion in established facial paralysis. A descending signal produced by direct stimulation to the contralateral motor cortex was able to elicit firing of the motor nucleus of the facial nerve, the extra-temporal portion of the peripheral nerve, and the orbicularis oris muscle. After achieving complete facial nerve paralysis, this descending signal was completely abolished within the temporal bone area, whereas peripheral facial nerve stimulation elicited a normal evoked electromyogram of the orbicularis oris muscle. The present results suggest that the site of the lesion of ischemic facial nerve paralysis produced by embolization in an animal model is within the temporal portion of the seventh nerve, and this animal model may lead to the advancement of future facial nerve research which cannot be conducted in humans. PMID- 1759582 TI - Is Pityrosporum ovale a pathogen of the external auditory meatus? AB - Fifteen dry wax samples, 15 wet wax samples and 7 dandruffy skin samples obtained from the external auditory meatus (EAM) of 26 individuals (age range from 1 to 76 years) were examined for the identification of Pityrosporum ovale. After staining the samples with Gram's stain, cultures were made on Sabouraud's medium with olive oil added. Thirteen of the dry wax samples, 1 of the wet wax samples and 6 of the dandruffy skin samples harboured P. ovale. Lipophilic yeast is frequently present in dry wax in adults and must be considered an aetiological agent of dandruff in the EAM. PMID- 1759583 TI - Macrophages on the nasal mucosal surface in provoked and naturally occurring allergic rhinitis. AB - Macrophages are the most common cell type residing in the lumen of the lower airways. However, very little is known about the presence and putative pathogenic implications of macrophages in the upper airways. Using specific immunohistochemical techniques, the presence of and changes in macrophage density were studied before and after allergen exposure in the laboratory and during natural allergen exposure of subjects with seasonal allergic rhinitis. The monoclonal antibody EBM 11 combined with the alkaline phosphatase-anti-alkaline phosphatase-technique was applied on cytospin-prepared slides. In the challenge experiment, 0.5 +/- 0.2% (mean +/- SEM; n = 10) of the total cell number were positive for the EBM 11 marker before challenge, thereby not differing from the controls (0.2 +/- 0.2%; mean +/- SEM; n = 3). Local allergen challenge induced an increase of these cells to a peak of 1.3 +/- 0.4% after 4 h (p less than 0.05). During seasonal exposure there was also a similar increase, from 0.7 +/- 0.2 to 1.3 +/- 0.3% (p less than 0.05; n = 11) in placebo-treated patients and from 0.7 +/- 0.2 to 1.6 +/- 0.4% (p less than 0.05; n = 11) in patients treated with topical glucocorticoids. There was, however, no direct relationship between nasal symptoms and number of macrophages present on the mucosal surface. The study indicates that macrophages are involved in the inflammatory processes of allergic rhinitis. PMID- 1759584 TI - Neutrophil elastase and its complex with alpha 1-antitrypsin in soluble and insoluble fractions of nasal secretions of chronic sinusitis. AB - Immunoreactive neutrophil elastase (NE) and its complex with alpha 1-antitrypsin (AT) was measured by double antibody enzyme linked immunosorbent assay (ELISA) in nasal secretions of chronic sinusitis (CS). Nasal secretions were separated into two fractions: PBS-soluble and insoluble fractions. Elastolytic activity was also examined. Mean value of total NE level was 31.0 micrograms/ml in the soluble fraction, which was significantly lower than that in the insoluble fraction (71.9 micrograms/ml, p less than 0.01). On the other hand, the percentage of complexed NE in total NE in the soluble fraction (33.7%) was significantly higher than that in the insoluble fraction (12.1%, p less than 0.01). Elastolytic activity in the soluble fraction (23.4 RFU) was significantly lower than that in the insoluble fraction (170.5 RFU, p less than 0.01). NE with elastolytic activity exists in nasal secretions of CS, and active-free NE in the insoluble fraction could be a major source of enhancement and continuation of mucosal inflammation. PMID- 1759585 TI - The effect of pilocarpine and atropine administration on radiation-induced injury of rat submandibular glands. AB - In the management of head and neck tumors by radiotherapy, the patients are prone to suffer from radiation-induced damage of the salivary glands. This experiment was carried out to examine the effect of pilocarpine and atropine on the rat submandibular gland and to establish whether it is possible to protect the salivary glands from irradiation by altering the amount of secretory granules in the serous cells prior to irradiation. The submandibular glands of rats were irradiated after pretreatment with or without drugs. Single irradiation of 18 Gy caused significant damage to the submandibular glands without pretreatment, showing the most severe changes 1 week after irradiation and slowly recovering thereafter. Pilocarpine pretreatment was protective against irradiation, displaying much less damage after irradiation of the same dosage, and with complete recovery after 4 weeks. On the other hand, atropine-pretreated animals revealed more extensive damage than the other two groups, possibly due to the retention of secretory granules. PMID- 1759586 TI - Occurrence of mast cells in relation to the distribution of nerve fibers in the rat larynx. AB - The distribution of mast cells in the rat larynx was studied at a light microscopic level in relation to nerve fibers showing substance P (SP)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) and ultrastructurally in relation to unmyelinated nerve fibers. Connective tissue mast cells (CTMC), demonstrated by staining for avidin-peroxidase and immunohistochemical staining for 5-hydroxytryptamine (5-HT), were localized in the lamina propria. Alcian blue and toluidine blue revealed mast cells in the epithelium and the lamina propria. The mast cells showed similar regional differences in their distribution as fibers showing SP- and CGRP-LI. A large or moderate number of cells was found on the laryngeal side of the epiglottis, in the ventral recess and in the aryepiglottic folds. No mast cells were found in the vocal cords. In addition, a large number of cells showing 5-HT-LI were observed in the subglottic epithelium but not in the supraglottic and the glottic epithelia. Ultrastructurally and by use of SP- and CGRP-immunohistochemistry, nerve fibers were sometimes observed close to the mast cells. These findings may be of importance in the understanding of laryngeal pathophysiological events. PMID- 1759587 TI - Laryngeal involvement in rheumatoid arthritis. AB - Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were studied in order to assess the prevalence of laryngeal involvement in patients with RA and the occurrence of extrathoracic airway obstruction. Laryngeal involvement was assessed by physical examination including direct fiberoptic laryngoscopy, respiratory function tests and low-voltage radiography. Physical examination revealed laryngeal involvement in 17 RA patients (59%), extrathoracic airway obstruction was indicated by spirometry in 4 (14%) and radiography revealed pathological findings in 3 patients (10%). One or more signs of laryngeal involvement were found in 20 patients (69%). Symptoms of breathing difficulties were common (75%) among patients with laryngeal involvement. The erythrocyte sedimentation rate and class-specific rheumatoid factors were not correlated to laryngeal involvement. PMID- 1759588 TI - Recurrent speech patterns as cues to the segmentation of multisyllabic sequences. AB - First and second language acquisition both require that speech be segmented into familiar, multiphonemic units (e.g., words and common phrases). The present research examines one segmentation cue that is of considerable theoretical interest: the repetition of fixed sequences of speech. On each trial, subjects heard repetitions ('pre-exposures') of two artificially-constructed, multisyllabic patterns that shared an embedded segment 1 or 2 syllables long (e.g., 2 shared syllables: [ga-li-SE] and [li-SE-stu]). There were 2 and 6, 4 and 4, or 6 and 2 repetitions of the two patterns, randomly ordered. Subjects were then to indicate the groupings they perceived within a subsequent, longer sequence containing both of the pre-exposed patterns (e.g., [ga-li-SE-stu]). Responses varied systematically with the size of the embedded segment, the repetition frequencies of the two pre-exposed patterns, and the serial position of each pre-exposure. The results illustrate how investigations of the processing of speech patterns may contribute to an understanding of some elementary aspects of language learning. PMID- 1759589 TI - Spatial topological constraints in a bimanual task. AB - Previous research has shown that the concurrent performance of two manual tasks results in a tight temporal coupling of the limbs. The intent of the present experiment was to investigate whether a similar coupling exists in the spatial domain. Subjects produced continuous drawing of circles and lines, one task at a time or bimanually, for a 20 s trial. In bimanual conditions in which subjects produced the circle task with one hand and the line task with the other, there was a clear tendency for the movement path of the circle task to become more line like and the movement path of the line task to become more circle-like, i.e., a spatial magnet effect. A bimanual circle task and a bimanual line task did not exhibit changes in the movement path when compared to single-hand controls. In all bimanual conditions, the hands were tightly temporally locked. The evidence of temporal coupling and concomitant accommodation in the movement path for the conditions in which the hands were producing different shapes suggests that spatial constraints play a role in the governance of bimanual coordinated actions. PMID- 1759590 TI - Kinematics of aiming in direction and amplitude: a developmental study. AB - The patterns of aimed movements to visual targets were analyzed in children aged 6, 8 and 10. Tasks with direction and/or amplitude requirements were used. The tasks were performed both with and without vision. Peak velocity, acceleration and deceleration and their relative temporal occurrence were evaluated. Overall, the 6- and 10-year-olds exhibited higher peak velocity and acceleration when performing the pure directional task than when performing tasks with an amplitude or stopping requirement. On the contrary, 8-year-olds showed similar peak acceleration and velocity across all three tasks. Similarly, when performing the pure directional task, the 6- and 10-year-olds reached their peak velocity and acceleration relatively later in time than the 8-year-olds. Vision of movement increased the peak velocity in all experimental tasks and peak acceleration was increased only in the pure directional task. Thus, movement kinematics varied according to the task requirements and age. Eight-year-olds showed greater propensity to feedback control in all tasks, suggesting an over-inhibition in their approach patterns, whereas 10-year-olds tended to use feedforward processes, with a shortened deceleration phase. PMID- 1759591 TI - Perceptual processing and speed-accuracy trade-off. AB - Three experiments are described on speed-accuracy trade-off during a visual fixation. In a typical trial subjects started by fixating a fixed position at their left side at which a degraded digit (SL) was presented. At about the same time an intact digit (SR) was briefly presented at a fixed right side position. SL and SR were separated by a binocular visual angle of 45 degrees. The task was to verbally report both digits, which implied that the eyes should be rapidly shifted from SL to SR, so as not to miss SR. Under these conditions the distribution of the fixation latencies of SL appeared to consist of two parts, suggesting the occurrence of either anticipations or reactions. This argues against a strategy of optional stopping of information accrual during the fixation of SL and is in line with a strategy of either fully neglecting or fully encoding SL. However, this interpretation meets the difficulty that, at trials where SL is reacted to, subjects showed a shorter fixation latency than in a control condition, in which they had ample time to view both SL and SR. The results of the second and third study supported the view that, when under time stress, subjects can end a fixation as soon as a preliminary code of SL is obtained. This code (a) is insensitive to the complexity of SL, (b) cannot be elaborated during the saccade to SR, and (c) can be used as a starting point for further analysis, as soon as the eyes reach SR. PMID- 1759592 TI - Knowledge acquisition and information searching strategies in diagnostic decision making. AB - The effect of three learning procedures on diagnostic information searching strategies was investigated. Undergraduate students acquired an artificial knowledge domain through either a Taxonomic-, Inductive-, or Case-oriented knowledge acquisition procedure. The use of the competing-hypotheses heuristic as a practical strategy to guide decision making in the face of uncertainty, was compared among the three learning conditions and between each condition and a non learning control group using the method developed by Kern and Doherty (1982) and Wolf et al. (1985). The small instruction intervention had an effect on the diagnostic nature of subjects' information-searching strategies. Subjects in the Inductive-learning condition exhibited a stronger tendency to seek diagnostically worthless information than the other learning conditions. The outcomes are considered relevant to the nature of expertise in decision making, and to the effect of instruction methodologies on the knowledge representations available to diagnostic classification and decision-making processes. PMID- 1759593 TI - GABA immunocytochemistry reveals five morphologically different nerve cell types in the frog stomach. AB - GABA (gamma-aminobutyric acid) immunocytochemistry was used on whole mounts of the frog stomach muscular layer to identify the GABAergic elements of the myenteric plexus. Between the labelled nerve fibres, five morphologically different types of neurons were revealed. The same cell types were also observed in the NADH-diaphorase-labelled control preparations. The different morphologies of the GABA-immunoreactive neurons may reflect the different peptide cotransmitter contents and/or different electrophysiological properties of these neurons. PMID- 1759594 TI - Acetyl-cholinesterase and mono-amine-oxidase activities in the microganglia of the thyroid gland in the rat. AB - The nervous microganglia of the thyroid gland have been studied in forty adult male rats, their morphology being analyzed by the osmium-zinc iodide technique their acetyl-cholinesterase activity (AChE) by an histochemical specific technique and their mono-amine-oxidase activity (MAO) by a tetrazolium technique. Few but constant microganglia were observed in the thyroid glands. These microganglia are formed by some 4 to 8 nerve cells. Intense mono-amine-oxidase activity (MAO) was found in the nerve cells of these microganglia, being absent in the rest of the thyroid gland. Intense specific acetyl-cholinesterase (AChE) was observed in the nerve cells scattered along nerve branches located in the connective tissue (single nerve cells or small cellular groups). AChE activity was not observed in the microganglia of the thyroid gland. PMID- 1759595 TI - Liliana Lubinska (1904-1990). PMID- 1759596 TI - Generalization of conditioned suppression during salicylate-induced phantom auditory perception in rats. AB - Tonal frequency generalization was examined in a total of 114 pigmented male rats, 60 of which were tested under the influence of salicylate-induced phantom auditory perception, introduced before or after lick suppression training. Thirty control subjects received saline injections, and the remaining 24 subjects served as noninjected controls of tonal background effects on generalization. Rats were continuously exposed to background noise alone or with a superimposed tone. Offset of background noise alone (Experiment I), or combined with onset or continuation of the tone (Experiments II and III) served as the conditioned stimulus (CS). In Experiment I, tone presentations were introduced only after suppression training. Depending on the time of salicylate introduction, a strong and differential influence on generalization gradients was observed, which is consistent with subjects' detection of salicylate-induced, high-pitched sound. Moreover, when either 12- or 3 kHz tones were introduced before or after Pavlovian training to mimic salicylate effects in 24 rats, the distortions in generalization gradients resembled trends obtained from respective salicylate injected groups. Experiments II and III were aimed at evaluating the masking effect of salicylate-induced phantom auditory perception on external sounds, with a 5- or a 10-kHz tone imposed continuously on the noise or presented only during the CS. Tests of tonal generalization to frequencies ranging from 4- to 11- kHz showed that in this experimental context salicylate-induced perception did not interfere with the dominant influence of external tones, a result that further strengthens the conclusion of Experiment I. PMID- 1759597 TI - Scopolamine-induced alterations in predatory behaviour pattern in cats. AB - Predatory behaviour in its full pattern (i.e., following the mouse, killing it and consuming the carcass) was tested in semi-natural conditions in cats. Consumption of minced horse meat was tested as well. Centrally acting scopolamine hydrobromide injected i.p. did not suppress predatory motivation, since following the prey and killing it were preserved. The executory phase of predation (i.e., the killing grip) was severely disturbed and the consumption of the mouse as well as meat was totally inhibited. Peripherally acting scopolamine methylnitrate administered into another group of cats under the same conditions generally did not affect predatory pattern, though meat and mouse consumption was disturbed to some extent. It is concluded that central muscarinic involvement in predatory behaviour in cats is limited to sensorimotor control of jaw movements. PMID- 1759598 TI - Hippocampal evoked field potentials and interictal spikes in hippocampally kindled cats. AB - Kindling-related changes of the hippocampal evoked field potentials and patterns of the spontaneous interictal spikes were investigated in 10 hippocampally kindled cats. A complex potential waveform was recorded by macroelectrodes placed in the CA3 region of the hippocampal gyrus and hilus of the gyrus dentatus, close to the granule cell layer, after stimulation of the entorhinal cortex. After high intensity repetitive (10/s) stimulation a late component could be recorded with the latency of about 30-40 ms, in addition to the early response originating in the gyrus dentatus. Probably this component developed during kindling into a delayed, high amplitude spike. After application of the double shock test, post stimulus facilitation of the spike response was observed within time limits of 20 100 ms. Another observation was a widespread, ipsilateral and bilateral long-term enhancement of the amplitudes of field potentials evoked by entorhinal and intrahippocampal stimulation. It was the most common effect observed during kindling. Widespread synchronized discharges of hippocampal spikes and localized clusters of brief irregular spikes were the most significant features of spontaneous interictal spikes. The paroxysmal discharges of spikes could be evoked by ipsi or by contralateral stimulation of the afferent pathways projecting to the kindled hippocampus, rather than by direct electrical stimulation of the kindled hippocampal gyrus. PMID- 1759599 TI - Cardiac frequency, phase and errors in one-dimensional sensorimotor tracking. AB - One dimensional manual tracking was investigated in relation to actual heart rate and phase of cardiac cycle. Higher heart rate was combined with increased tracking error incidence and decreased successful tracking time (light spot inside target). Error incidence was time-locked with respect to the phase of cardiac cycle. PMID- 1759600 TI - Effects of different intrastimulus interval on learning of the Konorski short term memory test in dogs. AB - A differentiation of instrumental responses to auditory location stimuli using the Konorski Test was investigated. Each stimulus consisted of two components separated by intrastimulus interval. The components were click series presented from four loudspeakers situated in front of the animal, on horizontal and vertical axes. Each correct response, performed to the second component of positive stimulus, was rewarded by food. Responses to negative stimuli were not reinforced. Solving the test was possible by comparing the memory trace of the first component location, with location of actually presented second component. Two groups of dogs were trained. In one group positive and negative stimuli were presented, in which intrastimulus interval lasted 1 s. In the other group, differentiation training included stimuli with intrastimulus interval lasting 3 s. Unexpectedly, the first group was unable to reach differentiation criterion, whereas the second group reached criterion without difficulty. The effect of reaching the criterion with longer and not shorter interval between stimulus components, may be specifically related to location cues as opposed to reported earlier auditory quality stimuli. PMID- 1759601 TI - Delayed response learning to visual stimuli in cats. AB - Six normally reared cats were trained on a three-choice delayed response task to visual stimuli. All cats mastered 1 min delay, three cats 2 min delay and one cat 6 min delay. Learning was much better than in previously studied cats reared in laboratory cages. It was comparable to that known for auditory stimuli in normally reared cats. PMID- 1759602 TI - Visually guided reaching for food in binocularly deprived cats. AB - Four visually deprived cats and four controls were tested in reaching for food from a cage. In each trial the animals in the groups responded immediately after unscreening the cage. However, in reaction time of forelimb extension the deprived group showed proportionally fewer responses with shorter reaction time than the control group. PMID- 1759603 TI - Formation of inositol polyphosphates in cultured adrenal chromaffin cells. AB - Formation of inositol polyphosphates has been characterized in cultured bovine adrenal chromaffin cells in terms of calcium dependency and isomers of inositol polyphosphates. There are two distinct pathways of generation of InsP3. Stimulants such as high K+ induce InsP3 accumulation by a calcium uptake dependent mechanism. Stimulants such as Ang II induce InsP3 accumulation by a calcium uptake-independent mechanism. Both mechanisms are involved in nicotinic stimulation. These results suggest that calcium entry as well as receptor mediated mechanisms play a significant role in phosphoinositides hydrolysis through phospholipase C in adrenal chromaffin cells. Nicotinic receptor stimulation induces a rapid and transient increase in Ins(1,4,5)P3 accumulation followed by a slower accumulation of Ins(1,3,4)P3. Moreover, nicotine induces a large and rapid increase in Ins(1,3,4,5,6)P5 accumulation with an extent and time course similar to Ins(1,4,5)P3, which peaks at 15 sec after stimulation. Nicotine also induced Ins(1,3,4,5)P4 and InsP6 accumulation with a slower time course and a lesser magnitude than Ins(1,3,4,5,6)P5. These results indicate that adrenal chromaffin cells possess fine regulation of inositol polyphosphates metabolism and that inositol polyphosphates are involved with the control of cellular function in these cells. PMID- 1759604 TI - Expression of G-protein alpha-subunit cDNA. PMID- 1759605 TI - Serotonin receptor subtypes in brain: ligand binding properties and coupling with G proteins. PMID- 1759606 TI - A cerebral endogenous factor regulates the activity of the serotonergic receptors modulating the neuronal release of acetylcholine. PMID- 1759607 TI - Serotonin receptor heterogeneity and the role of potassium channels in neuronal excitability. AB - Intracellular recordings in vitro from a variety of central neuronal types have shown both inhibition and excitation to be modulatory consequences of serotonin (5-HT) receptor activation. These responses can be seen in isolation or in some cases (e.g. hippocampal pyramidal cells) as a complex biphasic combination of hyperpolarisation followed by depolarisation, suggesting overall control of neuronal excitability may be dependent on the interaction between activation of more than one post-synaptic receptor and/or mechanism. Our studies have confirmed the 5-HT evoked depolarisation of rat facial motorneurones (FM's) and the hyperpolarisation seen in presumed serotonergic neurones of the dorsal raphe nucleus (DRN) to be the result of opposite effects on K+ ion permeability. Suppression of a resting K+ conductance leads to depolarisation while activation leads to hyperpolarisation. The same mechanisms appear to be responsible for the 5-HT evoked responses in hippocampal pyramidal cells but in addition there is also a suppression of a Ca++ dependent K+ conductance responsible for the long spike after hyperpolarisation (AHP). Data from the hippocampus and DRN indicate the 5-HT induced hyperpolarisation to be sensitive to Pertussis Toxin (PTX) and irreversibly mimicked by GTP gamma S, a non-hydrolysable analogue of GTP, suggesting the involvement of a G protein in K+ channel activation. The mechanism of K+ channel closure is less clear as it is unaffected by PTX or activation of adenylate cyclase, however there is indirect evidence that the phosphoinositide pathway may be involved from the cloned 5-HT1C receptor which also closes a K+ channel in cell lines. The results show that hyperpolarisation evoked by 5-HT in the hippocampus and DRN to be mimicked and blocked by 5-HT1A agonists and antagonists. However, the depolarisations in the hippocampus and FM's are mediated by site-dependent receptors with profiles which do not fit into the current 5-HT receptor subtype classification. PMID- 1759608 TI - Modulatory actions of norepinephrine on neural circuits. AB - A spectrum of studies has been conducted on a single aspect of NE function in which, through a beta-one receptor activation, NE appears to mediate a degree of physiological control over the gain of GABA mediated inhibition. It is significant that this single effect has been observed in numerous interrelated preparations ranging from single isolated Purkinje cells from young rats to adult Purkinje cells in awake locomoting rats. With respect to the functional conse quences of these effects, our best current speculation as to "what NE does" is that NE acts to regulate the strength of these tuned gating mechanisms in both cerebral and cerebellar cortices. There are numerous unanswered questions raised by the past work. One pressing issue is - when and for what reason in normal function does the modulation take place? When does NE release normally occur (is it phasic or tonic), and which of the demonstrated actions appears and for how long in relation to period of receptor activation? Does NE release cause the circuit to "react" to conditions which need "improved neurocomputation" or does NE stabilize the circuit to react predictably in the face of stress? Finally, what is the molecular sequence of events between receptor activation and an alteration of GABA receptor channel opening? What additional molecular control mechanisms exist and how can the diverse inhibitory and modulatory phenomena be reconciled, both short and long term? Issues are defined which need to be clarified at all levels of the current skeleton of basic understanding. Our prediction is that pursuit of these issues will benefit from an exchange of insight gained from investigations at all levels. PMID- 1759609 TI - Reversal of nigrostriatal-lesion-induced receptor alterations by grafting of fetal mesencephalic dopaminergic neurons. PMID- 1759610 TI - Depression of NMDA-evoked acetylcholine release by endogenous adenosine in striatum slices. AB - The mechanisms of NMDA-evoked transmitter release are still not clear. We demonstrate for the first time that NMDA-evoked acetylcholine release is depressed by endogenous liberated adenosine in functionally-hypoxic and non hypoxic brain slices. Adenosine deaminase potentiates the release of 3H acetylcholine from rat striatum slices in response to N-Methyl-D-Aspartate (NMDA) stimulation, whereas (-)-R-phenylisopropyl-adenosine (R-PIA) decreases the NMDA evoked transmitter release. The NMDA-evoked transmitter release is potentiated by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) only in adenosine depleted slices. The increase of extraneuronal adenosine by dipyridamole also depresses the presynaptic transmitter release. Our results indicate: (i) that stimulation of NMDA-receptors induces a complex neuronal response, e.g., release of acetylcholine and release of adenosine, (ii) that adenosine induces an agonist high affinity conformation of the A1-receptors which apparently are insensitive to an A1-adenosine receptor-antagonist (DPCPX) and (iii) that brain slices 0.5 mm thick can serve as an experimental model for testing antihypoxic substances. PMID- 1759611 TI - The nicotinic acetylcholine receptor gene family: structure of nicotinic receptors from muscle and neurons and neuronal alpha-bungarotoxin-binding proteins. PMID- 1759612 TI - Evidence for cardiovascular roles of tachykinin peptides in the brain of the rat. PMID- 1759613 TI - Affinity purification of nicotinic acetylcholine receptor from rat brain. PMID- 1759614 TI - Differential coupling of subtypes of the muscarinic receptor to signaling mechanisms in brain and peripheral tissues. PMID- 1759615 TI - The molecular properties of the M1 muscarinic receptor and its regulation of cytosolic calcium in a eukaryotic gene expression system. PMID- 1759616 TI - Molecular mechanism underlying the occurrence of supersensitivity at muscarinic receptors: analysis using cerebral cortical neurons in primary culture. PMID- 1759617 TI - Intramembrane particles in the postsynaptic membranes of the S-, F-, and C-type synapses by freeze-fracturing, and deep-etching studies on the Xenopus spinal cord. PMID- 1759618 TI - 123-I-iomazenil-SPECT in patients with focal epilepsies--a comparative study with 99mTc-HMPAO-SPECT, CT and MR. PMID- 1759619 TI - Comparative transfusion medicine. PMID- 1759620 TI - History of transfusion medicine. PMID- 1759621 TI - Histocompatibility and bone marrow transplantation. PMID- 1759622 TI - Preparation of components. PMID- 1759623 TI - Clinical transfusion medicine. PMID- 1759624 TI - Neonatal transfusion medicine. PMID- 1759625 TI - Autologous transfusion. PMID- 1759626 TI - Blood substitutes. PMID- 1759627 TI - Colony-stimulating factors: their biological activities and clinical promise. PMID- 1759628 TI - Appendix: blood cell values in selected mammals. PMID- 1759629 TI - White cells. PMID- 1759630 TI - Platelets and coagulation. AB - Hemostasis is a multiple-component system. In order to function properly it has become highly integrated with several strategies of control. Failure of the system or its control can result in life-threatening hemorrhage requiring transfusion. It is hoped that the information provided in this article has enhanced the reader's understanding of hemostasis in animals, and will enable the reader to make a more educated choice concerning transfusion therapy for the bleeding patient. PMID- 1759631 TI - Erythrocytes. PMID- 1759632 TI - [Complex oral rehabilitation of children with cleft lip-jaw-palate]. AB - The prerequisite for the full oral rehabilitation and social adaptation of cleft palate patients is a consistent, comprehensive care system, providing a well organised integration of preventive and interceptive measures, as well as close cooperation between the various specialised disciplines. Preventive stomatological care should begin in infancy. PMID- 1759633 TI - [Maxillofacial growth in difficult conditions: on orthodontic rehabilitation of patients with cleft lip-jaw-palate]. AB - The orthodontic treatment of cleft palate patients extends from birth to youth and is divided into three phases: pre-operative phase, deciduous dentition, mixed and permanent dentition. Therapeutic concepts for each particular phase are presented. Information is also provided on research into the growth of the jaw and face area in cleft palate patients compared with a control group. PMID- 1759634 TI - Prediction of the growth in patients with achondroplasia. PMID- 1759635 TI - [Disorders of growth and development in patients with osteogenesis imperfecta and their effects on the orofacial system]. AB - The results of stomatological examinations covering 16 children with osteogenesis imperfecta are reported. This disease is accompanied by typical symptoms in the oro-facial region. Dentinogenesis imperfecta occurred in 5 patients and can be considered an optional symptom of osteogenesis imperfecta. PMID- 1759636 TI - [AIDS in children: selected topics for pediatric practice]. PMID- 1759637 TI - [The practical significance of laterality]. AB - In the present review the practical relevance and the problems of left-handedness have been discussed. Nowadays the diagnosis of the correct hand for writing and learning to write are very important for left-handers. Laterality is a hybrid phenomenon which concerns not only pedagogics but also many other fields, such as medicine, transport, sport and art. PMID- 1759638 TI - [Catamnestic study of school children with behavioral disorders]. AB - A catamnestic study of disturbed pupils, who have been examined by a child neuropsychiatrist for admission to a balancing class, revealed that the accumulation of biological and psychosocial load factors presents a risk for persisting behavioural disturbance. Failure at school was prevented by a temporary stay in a balancing class, but psychic maldevelopment indicated by the high percentage of odd children in the disturbed population could not be precluded. The refore the life-long medical and special pedagogic care for these children beyond discharge from the balancing class is considered to be necessary. PMID- 1759639 TI - [Analysis of the public health status and assessment of vaccination status in maternal health services and child and adolescent preventive health care of a district city]. AB - A total of 23 maternity centres and 8 youth welfare centres in the county town of Magdeburg were inspected in 1987 and 1988 to review the condition of buildings and layout of rooms. Checks were also made on anti-infectious routines and compliance with the vaccination regulations. In all of these areas a number of deficiencies were found, and the results of follow-up inspections clearly show that the attention being given to public health regulations for sterilization and disinfection and to the storage of vaccines, is still inadequate. Urgent action is also required to improve conditions which are beyond the control of staff, such as buildings in need of repair, lack of space and the installation of washbasins, toilets, etc. PMID- 1759640 TI - [Primary hypogonadism associated with neuropsychiatric disorders]. AB - Among 43 female patients aged 17-46 years, most with severe oligophrenia, there were 4 with primary hypogonadism (olfactory-genital dysplasia, Smith-Lemli-Opitz syndrome and lastly a Kanner syndrome). The incidence of genital underdevelopment is assumed to be higher among mentally retarded female patients. In cases of hypogonadism and hypogenitalism a search should always be made for possible mental and neurological disorders. PMID- 1759641 TI - [Accommodation and the pupil]. PMID- 1759642 TI - [The parasympathetic direct pathway from the midbrain to the ciliary muscle in cats and monkeys]. AB - The visceral, namely the parasympathetic component of the oculomotor complex which directly innervates ciliary muscle was investigated using horseradish peroxidase (HRP) in three cats and three monkeys. A unilateral total iridectomy to abolish innervation to the iris was made in all animals. After 1 month to allow fiber degeneration in the iris, HRP was injected into the ciliary muscle of ipsilateral eye. Distribution of the labeled cells at the midbrain and at the ciliary ganglion was examined. Labeled cells were present in the ciliary ganglion and midbrain in all three cats and three monkeys. In the cat, labeled cells were distributed in the Edinger-Westphal (EW) nucleus and the Perlia nucleus. In the monkey, labeled cells were distributed in the anteromedian (AM) nucleus, the EW nucleus and the Perlia nucleus, respectively. Therefore, the existence of a direct parasympathetic pathway from the midbrain to the ciliary muscles was confirmed in these animals. Based on these observations, it is obvious that accommodation of the eye was innervated partly by a direct pathway from the midsagittal region of the parasympathetic neuron of the oculomotor nuclear complex. PMID- 1759643 TI - [Attempt to the measurement of the tension of zonular fibers--influence to the lens suspensory apparatus when the lens was vertically displaced by pushing posteriorly]. AB - A new fine pressure gauge was developed to quantitate zonular tension of the albino rabbit eye. This apparatus consists of a plastic rod to press the crystalline lens, transducer, amplifier, and recorder. The diameter of this plastic rod is 8 mm. The cornea and the iris of enucleated eyes were removed by excision in the limbus. Afterwards the lens were vertically pressed by the plastic rod of the fine pressure transducer. It was necessary to disrupt a part of zonules by approximately 106 g (2.11 g/mm2). This result was equivalent to 155 mmHg. The morphological changes of the anterior part of eye globe which consists of lens, zonules, and ciliary process were investigated using scanning electron microscopy. In the control eyes, the zonular fibers mostly originated from the superior or lateral ciliary processes and inserted straight into the equatorial region of the lens. In comparison with control eyes, the zonular fibers which were pressed by the plastic rod were almost absent within 1/6 of a circle. This disruption occurred at the region adjacent to the ciliary e process, while the region of the insertion to the lens demonstrated a normal appearance. In the unaffected area zonules were well-preserved morphologically, apart from splits of the bundles of zonules. The present study indicated that zonular fibers could resist a stretching press up to approximately 8 times normal intraocular pressure. PMID- 1759644 TI - [Topography of the human ciliary muscle]. AB - The human ciliary muscle of the eye of a 48-year-old male enucleated at surgery for an adenoid cystic carcinoma of the lacrimal gland was studied regarding the morphological characteristics of the anterior apical part of the muscle, including the three-dimensional microstructure. In the anterior serial transverse sections from the most anterior level in which the meridional, radial and circular muscle fibers were recognized, the circular muscle layer anteriorly decreased, whereas the radial muscle layer increased in ratio. Thick muscle fiber bundles immediately below the outermost meridional muscle fiber layer repeated to merge and divide with neighbouring bundles on every side and indicating a complicated structure. In the scleral spur, the apical part of the muscle fiber bundle showed a very thin lamellated layer and terminated between the stromal tissue of the scleral spur indicating a strong interconnection with stromal tissue by a muscle-tendon junctional structure basically similar to the muscle tendon junction in the striated muscle. PMID- 1759645 TI - [Observation of cellular communication in the corneal endothelium using a small molecular weight fluorescent dye]. AB - The metabolic and functional connection between corneal endothelial cells is thought to depend on the transfer of small molecules via gap junctions, as has been reported for other tissues. Cell-to-cell communication in the corneal endothelium was studied by monitoring the spread of fluorescence following the direct injection of Lucifer Yellow CH into single endothelial cells of the excised rabbit cornea. The image of the endothelial cells was observed during the injection and post-injection periods using specular microscopy and fluorescence microscopy. In the fresh cornea, the dye transferred readily from the injected endothelial cell to its neighbors. In damaged cells, dye transfer was slower or did not occur. After 5 hours of incubation in tissue culture medium 199, the specular microscopic image degraded, lowered cell membrane potential and decreased dye transfer rate were measured. This study showed that in normal corneal endothelial cells there were efficient cell communication channels between neighboring cells, and as the endothelium becomes less viable, cell communication is inhibited. PMID- 1759646 TI - [Lens crystallin leakage in aqueous humor from human cataractous lenses]. AB - The amounts of human lens crystallins in the aqueous humor from various types of cataract patients were measured by radioimmunoassay. alpha, beta and gamma crystallins as antigens for radioimmunoassay were purified from one-year-old normal human lens by TSK3000SW gel permeation column using high performance liquid chromatography. The amounts of both alpha- and gamma-crystallin in the aqueous humor from the patients with cortical and posterior subcapsular cataract were relatively low but in the case of mature cataract those of both crystallins increased. While the amounts of beta-crystallin in aqueous humor from cortical and posterior subcapsular cataract patients were at the same level compared with alpha-crystallin, those from mature cataract patients showed extremely high values. PMID- 1759647 TI - [Participation of sodium iodate in the induction of experimental autoimmune uveoretinitis (EAU)]. AB - It is known that Brown Norway (BN) rats show resistance to the development of experimental autoimmune uveoretinitis (EAU). Although BN rats don't develop EAU easily when they were immunized with S antigen containing emulsified complete Freund's adjuvant, this paper reports on the development of EAU at the rate of 40 60% in BN rats when immunization is preceded by an injection of more than 0.5 mg (1.79 mg/kg of body wt) of sodium iodate which leads to the destruction of retinal pigment epithelium (RPE). It was thought that the destruction of RPE participated in the induction of EAU. Therefore, it is considered that the existence of RPE may play an important role in the induction of EAU. PMID- 1759648 TI - [Correction of EOG with eye movement measured by the eye mark recorder system]. AB - The electrooculogram (EOG) is usually necessary for the subject to fixate two targets alternately at a fixed visual angle. However, in the patients with poor vision, it can be difficult to fixate exactly. In such case, the results can be improved by using both the measurement of real eye position and the measurement of EOGs in combination. In this study, we measured subject's eye position simultaneously with the potential changes around his eyes as the subject pursued alternately two on-and-off visual targets which were horizontally placed on the cylindrical screen at a regular visual angle in front of his eyes. The EOG is obtained from those potential changes. If the difference between the target position and the fixating point can be calculated from the net eye movement measured with an eye camera, the error potential can be derived from this difference. Therefore, exact potential changes are obtained by correcting the measured potentials with the above error potentials. The authors were able to confirm that the potential changes were approximately proportional to the amplitude of saccadic eye movements within about 30 degrees in front of the eyes. Therefore, the simultaneous measurement of the potential changes and the eye position enable measurement of EOG without pursuing the targets by transforming the measured potentials into the exact values corresponding to the constant amplitudes of saccades. PMID- 1759649 TI - [Studies on intraocular hydrogen ion concentration. The effect of diathermy coagulation for normal albino rabbits' eye]. AB - The vitreous and intra-retinal pH of anesthetized albino rabbits were measured using an antimony pH microelectrode (Micro Antimon pH Electrode No. 801, Diamond Electro-Tech Co. Ltd). The effect for the retinal pH was observed after regional choroidal circulatory disturbance was synthesized by trans-scleral diathermy. The results showed that the arterial blood pH was 7.45 +/- 0.03 (n = 24). The average vitreous pH was 7.41 +/- 0.11 (n = 24), which was almost equal to or slightly lower than that of the arterial blood. There were no statistical significance between the two. The average retinal pH was 7.31 +/- 0.11 (n = 22), which was lower statistically than that of the vitreous (p less than 0.01). The retinal pH was measured in the same way 3 weeks after the trans-scleral diathermy. Those within the coagulation scar showed pH value of 6.87 +/- 0.39 (n = 10). This is lower than those in a normal retina (p less than 0.01). This instrument allows continuous pH measurements of the intraocular tissue and therefore it is thought to be useful for the studies of retinal circulatory disturbances. PMID- 1759650 TI - [The effects on accommodative and pupillary responses by topical application of cyclopentolate hydrochloride]. AB - Accommodative and pupillary responses, refractive change, and visual acuity after 30 microliters instillation of cyclopentolate hydrochloride of various concentrations (0.00625-0.1%) in 6 young normal males (27.0 +/- 0.6 yrs) were investigated. Both accommodative and pupillary responses were measured by an infrared optometer, at pre-instillation and 1, 3, 6, 9 and 24 hours post instillation. No significant effects were induced by concentrations of cyclopentolate hydrochloride 0.0125% or less. Reduced amplitude of accommodation and enlarged pupil were, however, observed by 0.025% and 0.05% of cyclopentolate hydrochloride from 1 through 9 hours post-instillation. Miotic response in accommodation was also reduced from 1-6 hours at the same concentrations. A concentration of 0.1% cyclopentolate hydrochloride showed both reduction of accommodation amplitude and enlarged pupil for 24 hours after instillation. However, neither refraction nor visual acuity was affected by any concentration of cyclopentolate hydrochloride. The results suggest that cyclopentolate hydrochloride at concentrations up to 0.05% applied before sleep would not be accompanied by inhibitory effects on accommodation during the day. PMID- 1759651 TI - [Changes in the dark focus of accommodation in patients with asthenopia]. AB - The authors studied tonic accommodation in cases of asthenopia. The subjects consisted of ten college students, aged 20 to 22 years old as normal control and seven patients with asthenopia, aged 20 to 27. The dark focus of accommodation was measured with the infrared optometer before and after a 15 min sustained visual task. No significant differences were found between the two groups on the pre-task dark focus of accommodation. After the task, significant differences were found between the pre- and post-task dark focus of accommodation in patients with asthenopia. The results suggest that the patients with asthenopia are more susceptible to autonomic nervous system imbalance than healthy persons. PMID- 1759652 TI - [The aging of accommodative function and its pupillary response in VDT workers without subjective complaints]. AB - Using a computer-assisted infrared optometer with a pupillometer, we measured the accommodative function and its pupillary response in 81 female subjects (age: 31 55 yrs) without visual complaints who worked via visual-display-terminal (VDT). From these measurements we analyzed the following 6 parameters regarding accommodation, and investigated whether a correlation exists between age and each parameter. The six parameters were, (1) the amplitude of objective accommodation, (2) the refractive fluctuation at the resting state of accommodation, (3) the refractive fluctuation after receiving myopic stimuli, (4) the pupil area prior to myopic stimuli, (5) the maximum rate of constriction by accommodation, and (6) the rate of pupil area recovery after accommodation. Among these parameters, the amplitude of objective accommodation, the refractive fluctuation at the resting state of accommodation, the refractive fluctuation after receiving myopic stimuli, and the pupil area prior to myopic stimuli were significantly correlated with age (all parameters: p less than 0.001). The correlation coefficients (r) were -0.810, -0.591, -0.612 and -0.320 respectively. There was also some relationship between age and the rate of pupil area recovery after accommodation (r = 0.188, p = 0.018), but no statistically significant correlation between age and the rate of constriction by accommodation (r = 0.100). These findings suggest that the overall functional capability of accommodation decreases constantly with age, though the pupillary reaction induced by accommodation is not correlated well with age. PMID- 1759653 TI - [Pars plana lensectomy preserving a clear anterior capsule in vitreous surgery]. AB - The anterior capsule was preserved intact in pars plana lensectomy in 14 cases of pars plana vitrectomy carried out for proliferative diabetic retinopathy in 9 cases, sarcoid uveitis in one case, proliferative vitreo-retinopathy in 3 cases and retinal detachment with a giant break in one case. Follow-up periods ranged from 6 to 17 months, with a mean of 11 months. Simultaneous posterior chamber intraocular lens implantation anterior to the anterior capsule was performed in 7 cases, and in one case secondary implantation was performed 4 months later. In 11 cases anterior capsules remained clear and in 9 of them lens epithelial cells had been thoroughly removed up to the equator using a Terry squeegee. Posterior synechia occurred in 4 cases in which air or gas tamponade had been done. This method allows complete anterior vitrectomy and is adaptable not only to simultaneous but also secondary posterior chamber intraocular lens implantation. PMID- 1759654 TI - [Tissue plasminogen activator treatment of postvitrectomy pupillary fibrin membrane]. AB - Twenty-five micrograms of human recombinant tissue plasminogen activator (tPA) was injected via the corneoscleral limbus of 14 postvitrectomy aphakic eyes with prominent pupillary fibrin membranes. Fibrinolysis by tPA was initiated by thirty minutes after the injection, and the fibrin membrane was completely dissolved within sixty minutes. No toxicity attributed to tPA was observed clinically. Intraocular fluid was obtained during fluid-gas exchange after complete dissolution of fibrin and analyzed for decomposed fibrin products (FDP). Intraocular FDP was significantly higher (160 +/- 250 micrograms/ml) than normal after tPA treatment. Intraocular tPA administration is a potent modality to treat postvitrectomy fibrin membrane. Fluid-gas exchange must be performed to eliminate as much FDP as possible to reduce postoperative inflammation. PMID- 1759655 TI - [Choroidal detachment associated with rhegmatogenous retinal detachment and aqueous flare]. AB - The aqueous protein level (APL) in eyes of rhegmatogenous retinal detachment (RRD) combined with or without choroidal detachment (CD) was investigated using a laser flare-cell meter. The APL in eyes of RRD with CD was 70 times higher than in eyes of simple RRD. The APL increased suddenly with the appearance of CD and decreased rapidly in accordance with the disappearance of CD. The longer the CD continued, the higher the APL remained preoperatively as well as postoperatively. The APL in eyes of RRD with CD was still twice as high as in eyes of simple RRD 6 months after successful retinal reattachment. This marked and prolonged intraocular inflammation in eyes of RRD with CD might result in a poorer visual outcome. The extremely high APL might be caused by reflux of suprachoroidal protein through the uveoscleral route and/or venous protein through the trabecular meshwork due to ocular hypotony and possibly by diffusion of protein via posterior chamber and vitreous cavity due to the breakdown of the blood ocular barrier. PMID- 1759656 TI - [Morphometry of sacral neurons innervating the pelvic muscles. Experimental study]. AB - Sacral motoneurons of the pelvic muscles have been extensively studied in the rat (1,2). Few informations occur in the literature on their specific morphology and their interconnection. In an experimental study we have differentiated the neuronal mapping of the: bulbo-spongiosus (B.S.M.), ischio-cavernosus (I.C.M.), levator ani (L.A.M.), sphincter ani (S.A.M.) and sphincter urethrae (S.U.M.) muscles. Each different or both sided pelvic muscle of 30 wistar rats have been injected by a solution of horse-radish-peroxidase. Using this H.R.P. technique, the mapping of the marked neurons and compared to the different muscles has been performed on horizontal and transversal spinal cord sections. A statistical study using the "T" test compares the maximal and minimal diameters and the surface of the neurons. 1. Most of the muscles injected in one side left or right receive their innervation from the neurons located in the homolateral side of the spinal cord. 2. The B.S.M. and the S.A.M. receive, in part, an innervation from the opposite side. 3. The neurons of the B.S.M. and of the S.A.M. are located in the D.M. group of L5 - L6 segment of the spinal cord. Their diameters are significantly different but not their surfaces (+/- 940 mu 2). 4. The neurons of the I.C.M. and of the S.U.M. located in the D.L. group have an equivalent diameter and surface. 5. The neurons of the L.A.M. have the largest diameter but an equivalent surface to the others. This work on a mammalian model brings further informations on the mapping of the sacral innervation of the pelvic muscles and offers a comparative reference for Man. PMID- 1759657 TI - Primary localized amyloidosis of the urinary bladder. AB - A case is presented of a woman aged 78 with a primary location of amyloidosis of the bladder. The clinical symptoms and the cystoscopy initially suggested a vesical carcinomatous infiltration. PMID- 1759658 TI - Primary transitional cell carcinoma of anterior male urethra: a rare case. AB - We report a rare case of primary transitional cell carcinoma in a man aged 56 years old. Approximately 600 cases of primary carcinoma of the male urethra have been accumulated until today (1). The 30 to 50 per cent of these neoplasms originate in the anterior urethra and only the 15 per cent are of the transitional cell type (2). PMID- 1759659 TI - Leiomyosarcoma of urinary bladder. AB - The authors report one case of a leiomyosarcoma of the urinary bladder in a seventy-two-year-old man. The treatment was transurethral resection. There has been no evidence of recurrence or metastasis in more than a two-year follow-up. The literature is reviewed and the size of the tumor on the prognosis is discussed. PMID- 1759660 TI - [Ureteroscopic resection of a fibrous polyp of the ureter]. AB - From a new case of fibroepithelial polyp in a 41 year old woman, we reviewed literature on this rare and benign pathology, for which differential diagnosis with malignant tumor is most often obtained surgically. We emphasize both diagnostic and therapeutic advantages of endoscopic approach of this lesion. PMID- 1759661 TI - [Transuretero-pyelostomy for ureteral necrosis following a Mainz continent umbilical urinary diversion]. AB - A female patient, undergoing a radical cystectomy and a continent urinary diversion in the umbilicus (after multiple gynecological interventions and 40 Gy radiotherapy) presented a stenosis of the left ureter. After 6 months a uretero pyelostomy (left-right) was performed mediating a bilateral lumbotomy. This approach has prevented a nephrectomy or a laparotomy which could compromise the continence mechanism of the pouch. PMID- 1759662 TI - [Endovesical antireflux plastic surgery. Original technique]. AB - The authors present a technique of endovesical transposition of the urethra with orthotopic reimplantation of latter. This very effective technique is simple. In addition, it allows secondary catheterization and reduces post-operative complications. PMID- 1759663 TI - [Prosthetic replacement in a case of invasion of the inferior vena cava by a recurrent hypernephroma]. AB - We report a case of inferior vena cava resection and reconstruction for recidivant renal cell carcinoma. We describe the collateral circulation of the renal veins and its importance in the treatment of inferior vena cava involvement. We debate of the indications and of the different surgical techniques for reconstruction of the inferior vena cava. PMID- 1759664 TI - The role of imaging techniques in diagnostic evaluation of angiomyolipomas. AB - Renal AML are rare benign tumors of the kidneys consisting of fat tissue intermixed with thick-walled blood vessels and smooth muscle. Due to the easy access to modern imaging techniques more and more AML are detected incidentally during diagnostic evaluation of common urological disease before getting symptomatic (mostly flank pain, hematuria). The presence of a highly echodense renal mass on ultrasound and the detection of even small amounts of fat in CT usually allows to establish the diagnosis of AML. If these procedures give still equivocal results, angiography and MRI may become necessary. When report a case of a patient with AML where all the imaging techniques including magnetic resonance were nonconclusive. The correct diagnosis could only be established by histological examination after surgical resection. Indeed, the presence of a large hematoma had masked all the characteristic features of AML in this case. PMID- 1759665 TI - The use of prostaglandins for diagnosis and treatment of erectile impotence. AB - The authors present their experience in using PGE-1 for the assessment of 77 impotent patients. This drug can be safely used as a screening test for vasculogenic impotence but is also useful in more invasive diagnostic tests. PGE 1 is probably the only natural product that can be used commonly for the treatment of erectile impotence, because it is a safe and effective drug. PMID- 1759666 TI - Endopyelotomy. Evaluation of a limited experience. AB - Endopyelotomy is a recently developed endo-urological technique which gets to be standardised and gradually may replace the open pyeloplasty. Our technique is described and the early results are presented. PMID- 1759667 TI - [Correction of ureteropelvic junction syndrome: Anderson-Hynes method of pyeloplasty with or without nephrostomy]. AB - We report the last 50 ureteropelvic junction repairs (Anderson-Hynes pyeloplasty) with a minimum follow-up of 6 months performed in our department. We describe the operative technique without nephrostomy in 40 patients and we look at the results in relation to a small group which had a nephrostomy for one or other reason (10 patients). PMID- 1759668 TI - [The treatment of prolonged erections using phenylephrine]. AB - Phenylephrine was used intracavernously to treat prolonged erections in 38 cases. A rapid detumescence was obtained in every case. Phenylephrine seems to be superior to all other adrenergic drugs in reason of its rapid action and its lack of side effects. PMID- 1759669 TI - Adrenal cyst: a case report. AB - The authors describe the case of a patient with a large adrenal cyst. They review the existing literature and discuss the problem of diagnosis an treatment. PMID- 1759670 TI - [Dermoid cyst of the bladder. Case report]. AB - Dermoid cyst of the bladder is an exceptional pathology. One case of hairy bladder tumors is describe with short review of the literature. PMID- 1759671 TI - [Observations of a case of sirenomelia in a 37-year-old adult]. AB - The authors study a case of sirenomelia at a 37 years old adult woman, nosographic table presented for the first time by Charles Duhamel in 1959, having the denomination of "caudal regression syndrome", similar to Goldenhar syndrome cephalic expression of this regression. The malformation is known and well presented by Greek mythology in Homer (Odissey), Ovide (The Metamorphosis) etc. One presents little enough information, its classification and a few etiopathology data. PMID- 1759672 TI - [Retroperitoneal fibrosis. Apropos of 3 cases 2 of which were induced by bromocriptine]. AB - The authors present three cases of retroperitoneal fibrosis. Two of which were induced by bromocriptine (PARLODEL). These three cases followed up for three years without recurrence were treated with corticoids and internal derivations (double J catheters) in two of the three cases. PMID- 1759673 TI - Drug approval process changing, speakers say. PMID- 1759674 TI - Chronotherapeutics: implications for drug therapy. PMID- 1759675 TI - Community pharmacy residencies refine career goals. PMID- 1759676 TI - Case report: 'pitfalls' associated with multiple NSAID use. PMID- 1759677 TI - Chronic complications of diabetes. PMID- 1759678 TI - Why APhA should reject its code of ethics. PMID- 1759679 TI - Clonal development of interconnected germ cells in the rat and its relationship to the segmental and subsegmental organization of spermatogenesis. AB - Segments and subsegments are the smallest unit of synchrony thus far described within longitudinal sections of seminiferous tubules. It is known that cells in a clone joined by intercellular bridges are at the same phase of development and are also thought to be units of synchrony. This study was designed to determine if it is possible that the synchrony seen in cells joined by intercellular bridges is the same as that cataloged along the long axis of the seminiferous tubule. In the present study, the maximum number of rat spermatids joined by intercellular bridges (a clone) was obtained. It was hypothesized that if the clone size were larger than the smallest known units of synchrony (segments or subsegments) in the long axis of the seminiferous tubule, then intercellular bridges would most likely govern the synchronous development of segments or subsegments (or finer subdivisions thereof). If the clone size is smaller than the number of cells present in a segment or subsegment, then other factors must govern synchrony in the longitudinal aspect of the tubule. In the determination of spermatid clone size, rat testes were injected with cytochalasin D which opens intercellular bridges of a spermatid clone to produce large symplasts. The number of nuclei in the symplasts was determined from serially sectioned tissue, by drawing nuclei with a camera-lucida, and by counting nuclei. After extensive examination of tubules, the number of spermatids found in the suspected five largest clones observed was determined to be 650, 607, 338, 240, and 177.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759680 TI - Localization of boar sperm proacrosin during spermatogenesis and during sperm maturation in the epididymis. AB - The localization of proacrosin was determined by using colloidal gold labeling and electron microscopy of boar germ cells during spermiogenesis to post ejaculation. Proacrosin was first localized in round spermatids during the Golgi phase of spermiogenesis; it was associated with the electron-dense granule, or acrosomal granule that was conspicuous within the acrosome. It remained within the acrosomal granule during the cap and acrosome phases of spermiogenesis. At these stages, there was no apparent association of the proacrosin molecule with the acrosomal membranes. During the maturation phase of spermiogenesis, proacrosin was seen to become dispersed into all regions of the acrosome except the equatorial segment. When sperm from different segments of the epididymis and ejaculated sperm were examined, localization was observed throughout the acrosome except for the equatorial segment. Here proacrosin appeared to be localized on both the inner and outer acrosomal membranes as well as with the acrosomal matrix, although further studies are required to verify the membrane localization. No labeling was seen on the plasma membrane. These data suggest that the synthesis and movement of proacrosin to sites in the acrosome are controlled by an as yet unknown process. The absence of proacrosin on the plasma membrane of mature ejaculated sperm makes it unlikely that this enzyme plays a role in sperm-zona adhesion prior to capacitation. PMID- 1759681 TI - Short-term morphological response of the rat testis to administration of five chemotherapeutic agents. AB - As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility. Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy. Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident. All except one chemotherapeutic agent (5-FU) caused spermatogonial damage. Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU). Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX). The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific. PMID- 1759682 TI - Testis structure in the sys (symplastic spermatids) mouse. AB - Testes of mice with the recessive insertional mutation termed symplastic spermatids (sys) were assessed for structural and developmental abnormalities. Homozygous (sys/sys) males are infertile due to an abnormality in spermatogenesis leading to azoospermia. The major interruption to spermatogenesis occurs when the intercellular bridges that connect round spermatids open prematurely resulting in the formation of symplasts. Symplasts contain as many as 285 nuclei. Development of spermatids within symplasts is arrested just before, or just after, elongation of the spermatid nuclei begins. Symplasts degenerate and appear to be phagocytized by Sertoli cells and by intratubular macrophages. In addition, degeneration of young round spermatids and also spermatocytes occasionally is observed. Spermatocyte degeneration is substantial in some tubules and leaves them depleted of cells other than basal compartment cells. Sertoli cell abnormalities are prominent and include intracellular vacuolation, absence of apical processes surrounding round spermatids, degeneration, and occasional sloughing. Although reduplication and infolding of the basal lamina is also seen, this does not appear as a common phenomenon. The sys phenotype is first manifest in animals between 19 days and 22 days of age. Considerable variability is seen in testis histology of prepubertal animals; some display degenerating pachytene spermatocytes and virtually no Sertoli cell vacuoles, while others display vacuoles without apparent elevated numbers of degenerating spermatocytes. Although this study has not revealed the primary cell type(s) affected by the insertional inactivation event, it is possible that the abnormalities in the Sertoli cells are responsible for germ cell degeneration as it is generally recognized that deficits in the Sertoli cell can result in major germ cell abnormalities but not vice versa. PMID- 1759683 TI - Structural characteristics of immature rat Sertoli cells in vivo and in vitro. AB - The structural properties of pelleted prepubertal Sertoli cells (pre-culture pelleted cells) from 19-day-old rats and of similar cells cultured for 7 days were compared with Sertoli cells from the intact animal (testis tissue from 19- and 26-day-old rats, the in vivo groups). Sertoli cells from freshly isolated pellets and those cultured for 7 days were similar in cell and nuclear volumes to their in vivo counterparts. Cell volumes, organelle volumes, and organelle volume densities of newly isolated Sertoli cells were similar to those of sectioned cells taken from the 19-day-old in vivo group, indicating that the procedure for isolation does not grossly alter Sertoli cells. Mean height of cells cultured for 7 days was significantly lower than that of cells from intact animals at 19 and 26 days of age. In vivo, Sertoli cells of 26-day-old animals displayed increased organelle volumes and organelle surface areas compared with those from 19-day-old animals; volume densities and surface densities remained relatively constant, indicating that in vivo, organelle growth is in proportion to growth of the cell. Most organelle volume and surface densities were not significantly different when 19-day-old in vivo cells and pre-culture pelleted cells were compared. Many organelle volume and surface density values were significantly less in cells grown in culture for 7 days as compared to freshly isolated pelleted cells. After 7 days of culture, most Sertoli cell organelles were significantly less in both volume density and surface density, as compared to the in vivo cell groups (19 or 26 day). This indicates that in vitro the organelles do not develop in proportion to the growth of the cell. After 7 days in culture, the absolute volumes and surface areas of the organelles remained generally unchanged as compared to cells from 19-day-old animals. The data show that Sertoli cells grow in volume in vitro like their in vivo counterparts; however, their subcellular features, although well maintained, do not develop in proportion to the cell. This suggests that short-term cultures are a more ideal system in which to study biochemical responses. Also, cultured prepubertal Sertoli cells are most appropriately used to study prepubertal Sertoli cell function. This is the first study to quantify developmental changes in Sertoli cell structure in vivo as well as to compare them with cellular changes occurring in vitro. PMID- 1759684 TI - Reinitiation of spermatogenesis by exogenous gonadotropins in a seasonal breeder, the woodchuck (Marmota monax), during gonadal inactivity. AB - The present study was undertaken (1) to document structural and functional changes in the testes of seasonally breeding woodchuck during active and inactive states of spermatogenesis and (2) to evaluate the ability of exogenous gonadotropins to reinitiate spermatogenesis outside the breeding season. During seasonal gonadal inactivity, there were significant (P less than 0.05) reductions in volumes of several testicular features (testis, seminiferous tubules, tubular lumen, interstitial tissue, individual Leydig cells, Leydig cell nuclei, and Leydig cell cytoplasm) as compared with gonadally active animals. The diameter of the seminiferous tubules was decreased by 26%, and Leydig cell numbers also declined in the regressed testes. These changes were accompanied by a decline in testosterone (T) levels in both plasma and testis, and reduction in epithelial height of accessory reproductive organs. A hormonal regimen was developed that would reinitiate spermatogenesis in captive, sexually quiescent woodchucks. A combination of PMSG and hCG markedly stimulated testicular growth and function and restored spermatogenesis qualitatively. Quantitatively normal spermatogenesis was restored in 2 of 6 treated males. Morphometric analyses revealed substantial increases in seminiferous tubular diameter and in the volume of seminiferous tubules, tubular lumen, total Leydig cells, and individual Leydig cells in the hormone-treated animals. These increased values corresponded to 99, 75, 68, 51, and 200%, respectively, of the values measured in naturally active woodchucks. Leydig cell numbers, however, remained unchanged and approximated only 31% of the number found in naturally active testes. Hormonal stimulation also resulted in a significant rise in serum T as well as in the total content of testicular T, and a marked increase in epithelial height in various accessory reproductive glands. The most effective hormonal protocol for stimulating spermatogenesis was treatment with 12.5 IU of PMSG twice a week for 4 weeks followed by 12.5 IU of PMSG + 25 IU of hCG twice a week for 4 weeks. PMID- 1759685 TI - Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis in rodents. AB - Structural features of the mouse and rat manchette and the role of the manchette in shaping the spermatid nucleus were investigated. Rod-like elements about 10 nm in diameter and 40-70 nm in length were seen linking the innermost microtubules of the manchette and the outer leaflet of the nuclear envelope in step 8 through step 11 rat and mouse spermatids that either had been routinely fixed for electron microscopy or had been isolated and detergent extracted. Rod-like linkers were also seen joining the nuclear ring to the plasma membrane and nuclear envelope. These linkers may ensure that under normal conditions the manchette remains in a defined position relative to these membranous components. A variety of compounds (taxol, cytoxan, and 5-fluorouracil) were found to perturb the manchette and to affect nuclear shaping. In addition, sys and azh mutant mice were used to determine the consequences of defective manchette formation. These genetic conditions and chemical treatments either produced manchettes that were not in their normal position (azh, sys, and taxol) and/or caused the manchette to appear abnormal (azh, sys, cytoxan, 5-fluorouracil, and taxol), and all resulted in a deformation of the step 9-11 spermatid nucleus. In all instances where the manchette was present, either in normal or ectopic locations, the sectioned nuclear envelope was parallel to the long axis of the microtubules of the manchette. In general, areas of the nuclear envelope where the manchette was not present, or where it was expected to be present but was not, were rounded (normal animals, sys, cytoxan). In addition, there are indications using certain compounds (cytoxan and 5-fluorouracil) as well as in the azh and sys mouse that the manchette may exert pressure to deform the nucleus. It is suggested that the rod-like linkages of the manchette ensure that the nuclear envelope remains at a constant distance from the manchette microtubules and that this is a major factor acting to impart nuclear shape changes on a region of the head caudal to the acrosome during the early elongation phase of spermiogenesis. The manchette microtubules, which are also known to be linked together, may act as a scaffold to deform this part of the nucleus from its spherical shape, perhaps in concert with forces initiated by other structural elements. Evidence from sys animals indicates that structural elements, such as the acrosomal complex over the anterior head (acrosome-actin-nuclear envelope), may affect nuclear shaping over the acrosome-covered portion of the spermatid head.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1759686 TI - Chorioallantoic placenta formation in the rat: I. Luminal epithelial cell death and extracellular matrix modifications in the mesometrial region of implantation chambers. AB - On days 7 and 8 of pregnancy, mesometrial regions of rat gestation sites were examined by light microscopy and transmission electron microscopy to determine what changes occur before the chorioallantoic placenta forms in that region. By day 7, gestation sites contained a uterine lumen mesometrially and an antimesometrial extension of the uterine lumen, the implantation chamber. The implantation chamber consisted of a mesometrial chamber between the uterine lumen and the conceptus, an antimesometrial chamber that contained the conceptus, and a decidual crypt antimesometrial to the conceptus. Stromal cells that formed the walls of the implantation chamber were closely packed decidual cells, while those that surrounded the uterine lumen were loosely arranged. Late on day 7, a portion of the epithelium lining the mesometrial chamber was degenerating, but this area of initial degeneration was never adjacent to the antimesometrial chamber. By early day 8, most of the epithelial cells lining the mesometrial chamber were degenerating and were being sloughed into the chamber lumen. Although degeneration of these epithelial cells morphologically resembled necrosis, it was precisely controlled, since adjacent epithelial cells lining the uterine lumen remained healthy. The space that separated the denuded luminal surface of the mesometrial chamber from underlying decidual cells became wider and was occupied by an extracellular matrix rich in cross-banded collagen fibrils. Decidual cell processes, that earlier had penetrated the basal lamina beneath healthy epithelial cells, protruded into this matrix and penetrated the basal lamina at the luminal surface. By late day 8, large areas of denuded chamber wall were covered with decidual cell processes, little remained of the basal lamina, and cross-banded collagen fibrils were scarce in the area occupied by decidual cell processes. During the times studied, uterine tissues that formed the walls of the mesometrial chamber were not in direct contact with the conceptus. This study indicates that trophoblast does not play a direct role in epithelial degeneration, basal lamina penetration, or extracellular matrix modifications in the mesometrial region of implantation chambers where part of the chorioallantoic placenta forms, although trophoblast may be required to trigger or modulate some of the changes. PMID- 1759687 TI - The role of hematogenous and intrinsic precursor cells in lymphocyte production in murine bone marrow and thymus. AB - It is well recognized that the bone marrow contains cells that can repopulate a depleted thymus as well as cells that can be induced to express phenotypic markers characteristic of T cells. It is not known, however, to what extent thymocytopoiesis in the normal thymus relies on immigrant, bone marrow-derived cells, nor whether some T cell precursors have entered the bone marrow from the circulation. We used the parabiotic system to test whether thymocytopoiesis relies on progenitors intrinsic to the thymus or on cells that enter the organ from the circulation. In the same system, we have also investigated whether Thy-1 bone marrow lymphocytes that respond to phytohemagglutinin (PHA) by proliferation and Thy-1 expression are produced by myelogenous or hematogenous progenitors. Syngeneic CBA/HT6 and CBA/CaJ mice were joined in parabiotic union at 4-6 weeks of age. Cross circulation between the two partners was verified by the equilibration of Evans' blue dye injected into one partner and by the equilibration of PHA-responsive T cells in the spleen of the parabionts. Chromosome spreads were prepared from the PHA-stimulated T cell-depleted bone marrow and from spontaneously proliferating thymocytes as well as from thymocytes stimulated by PHA or Concanavalin A (Con A). The exchange of spleen colony forming units (CFU-S) in the femoral marrow was assessed by karyotyping individual spleen colonies. Regardless of the length of parabiotic union, ranging from 4 to 20 weeks, Thy-1-, PHA-responsive bond marrow lymphocytes remained predominantly of the host type with only 3% being derived from the opposite partner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759688 TI - Arrangement and innervation of the iliocostalis and longissimus muscles of the brown caiman (Caiman crocodilus fuscus: Alligatoridae, Crocodilia). AB - The axial musculature of the brown caiman was investigated in detail with particular attention to the nerve supply, using a binocular stereomicroscope. Due to the prominent development of the longissimus (Lo) and the iliocostalis (IC) muscles of the caiman, the pattern of distribution of the spinal nerves in the body wall was unique; there also was less differentiation of the external intercostalis. There were four primary divisions of the spinal nerves in the thoracic region of the caiman, from ventral to dorsal: the intercostal nerve, the IC nerve, the Lo nerve, and the dorsal main trunk. Thus, the classic concept of the organization of the spinal nerves may not be suitable for the caiman. These findings suggest that evolutionary changes in the dorsolateral axial musculature have brought about the rearrangement of the organization of the spinal nerves. In addition, each clearly segmented myotome of the Lo and IC was innervated by more than two segments of the spinal nerves (plurisegmental innervation). The manner of formation of the myotome and its innervation is discussed from the viewpoint of comparative and developmental anatomy. PMID- 1759689 TI - Hypophyseal angioarchitecture of common tree shrew (Tupaia glis) revealed by scanning electron microscopy study of vascular corrosion casts. AB - The vascular corrosion cast technique in conjunction with scanning electron microscopy (SEM) was used for the study of pituitary microvascularization in the common tree shrew (Tupaia glis). The pituitary vascular casts were obtained by infusion of low viscosity methyl methacrylate plastic (Batson's no.17) mixture. It was found that the blood supplies to the pituitary complex were from branches of the circle of Willis and could be divided into two groups. The first group consisted of two to four superior hypophyseal arteries (SHAs) branching off from the internal carotid artery supplying each half of the median eminence (ME), infundibular stalk (IS), and pars distalis (PD). The SHAs supplying the ME branched into internal and external capillary plexi. The internal plexus had a larger capillary size (approximately 15 microns in diameter), was deeper in position, and had denser and more complex capillary loops than those in the external plexus. The capillaries of the external plexus were approximately 10 microns in diameter. The two plexi drained into 15-20 hypophyseal portal veins (HPVs) which were located mainly along the ventral and ventrolateral surfaces of the IS before breaking up into large capillaries (approximately 18 microns in diameter) with an anteroposterior arrangement within the PD. The second group consisted of one inferior hypophyseal artery (IHA) on each side branching off from the internal carotid artery. These arteries gave off branches to pierce the dorsolateral and ventrolateral aspects of infundibular process (IP) before branching off to form a capillary network. They also gave rise to radiating capillaries to supply the pars intermedia (PI) surrounding the cortical area of the IP. The hypophyseal cleft separating the PI from the PD was clearly seen with very few blood vessels. The capillaries in both PD and IP joined to form confluent hypophyseal veins draining the blood into the cavernous sinus. PMID- 1759690 TI - Congenitally osteosclerotic (os/os) rabbits are not cured by bone marrow transplantation from normal littermates. AB - The osteopetrotic (os) rabbit is a lethal mutation of autosomal recessive inheritance characterized by hypocalcemia, hypophosphatemia, fibrosis of marrow spaces, and ultrastructural abnormalities in both osteoclasts and osteoblasts. Procedures involving the transplantation of cells from normal hemopoietic tissues, which are sources of osteoclast precursors, are known to cure osteopetrosis in several mutations including some children. We tested the ability of transplanted bone marrow and/or spleen from normal littermates to reverse the skeletal sclerosis in os rabbits. Treatment of 15 neonatal mutants consisted of immunosuppression by whole-body irradiation followed by transplantation of normal bone marrow and/or spleen cell suspensions. This treatment failed to prolong life span or to cure osteopetrosis judged radiographically and histologically for up to 3 weeks posttreatment, the longest time of survival. These data indicate that transplantation of stem cells from multiple hemopoietic tissues, procedures known to cure osteopetrosis in other mutations, is not effective in the os rabbit. These results support the hypothesis that the skeletal microenvironment is not capable of supporting the development and function of normal osteoclasts in this mutation. PMID- 1759691 TI - Structure-function relationships during preovulatory development of porcine follicles following equine chorionic gonadotropin stimulation. AB - Porcine follicular maturation begins by recruitment from a continually proliferating pool of small antral follicles; those receiving the appropriate stimulus differentiate rapidly through a series of structural and functional changes. Such ovarian activity can be induced in prepubertal gilts with a single injection of equine chorionic gonadotropin (eCG). Average follicular diameter in eCG treated females increased from approximately 2 mm before stimulation to 3.5 mm by 24 hr after injection, with subsequent growth to ovulatory size (8 or 9 mm) by 96 hr. Both theca and granulosa layers increased in thickness and complexity, and a prominent capillary bed evolved immediately outside the basement membrane separating the two layers. Cytoplasmic organelles associated with increased metabolic activity and steroidogenesis proliferated within the first 24 hr. Progressive changes included increasing amounts of lipid and rough and smooth endoplasmic reticulum, with the latter occurring in vesicular or lamellar forms and as lipid-associated whorls. Bizarre mitochondrial forms also appeared, often associated with lipids. The amount and proportion of rough and smooth endoplasmic reticulum shifted dramatically as follicles matured. By 24 hr, rough endoplasmic reticulum in thecal cells increased from 4.2 to 7% of cell volume, while the amount in granulosa cells increased from less than 3.5% to more than 10%; the quantity remained relatively constant in the theca but declined to prestimulation values in the granulosa layer. Rough endoplasmic reticulum predominated over smooth in the first 24 hr following stimulation but the proportions were then reversed, so that more than 10% of both layers was composed of smooth endoplasmic reticulum by the time ovulation was imminent. Some follicles had or were in the process of ovulating by 96 hr. Their walls were collapsed into prominent folds with the two cell types beginning to mix. Slight undulations and some regions of discontinuity were observed in basement membranes of large unovulated follicles at this time. In specimens collected at 96 hr poststimulation and processed for retention of lipid, lipid-like material was noticeable in the extracellular matrix surrounding cells that contained organelle configurations suggestive of steroidogenesis. PMID- 1759692 TI - Sensory innervation of the canine esophagus, stomach, and duodenum. AB - The sensory innervation of the postpharyngeal foregut was investigated by injecting the enzyme horseradish peroxidase (HRP) into the walls of the esophagus, stomach, or duodenum. The transported HRP was identified histochemically, labeled neurons in the spinal and vagal ganglia were counted, and the results were plotted using an SAS statistical program. The spinal sensory fields of each viscus were defined using three determinations: craniocaudal extent, principal innervation field, and peak innervation field. The data revealed that innervation fields are craniocaudally extensive, the sensory field of each viscus overlaps significantly with its neighbor, yet each viscus can be characterized by a field of peak innervation density. Craniocaudal innervation of the esophagus spans as many as 22-23 paired spinal ganglia (C1-L2). There are two peak innervation fields for the cervical (C2-C6 and T2-T4) and for the thoracic (T2-T4 and T8-T12) sectors of the esophagus. The sensory innervation of the stomach extends craniocaudally over as many as 25 paired spinal ganglia (C2-L5). The peak innervation field of the stomach spans a large area comprising the cranial, middle, and the immediately adjoining caudal thoracic ganglia (T2-T10). The duodenum is innervated craniocaudally by as many as 15 paired thoracolumbar ganglia (T2-L3). Peak innervation originates in the middle and caudal thoracic ganglia and cranial lumbar (T6-L1) ganglia. There is a recognizable viscerotopic organization in the sensory innervation of the postpharyngeal foregut; successively more caudal sectors of this region of the alimentary canal are supplied with sensory fibers from successively more caudal spinal dorsal root ganglia. Vagal afferent innervation of the esophagus, stomach, and duodenum is bilateral and originates predominantly, but not exclusively, from vast numbers of neurons in the nodose (distal) ganglia. The esophagus is innervated bilaterally and more abundantly by jugular (proximal) ganglia neurons than is either the stomach or duodenum. The physiological significance of the findings are discussed in relation to the phenomena of visceral pain and referred pain. PMID- 1759693 TI - The vasculature of the rat penis: a scanning electron microscopic and histologic study. AB - As a basis for understanding the mechanism of erection in an animal model frequently used in research in reproductive biology, the angioarchitecture of the penis of the rat has been described using scanning electron microscopy. Study of the penile vasculature of the rat indicates that the corpora cavernosa penis and the corpus spongiosum are independent erectile tissues, each with its own arterial and venous vessels. The large vascular spaces and abundant smooth muscle of the penile crura are compatible with its role in regulating blood flow to more distal penile tissues. Helicine arteries of the crura, but not the parent deep penile artery or arteries elsewhere, have muscular cushions in their walls. The venous drainage of the penile crura is via subtunical veins which are thought to be compressed during erection to elevate pressure within the penis. Large, paired cavernous veins drain the shaft of the penis. A unique method for inhibiting blood flow from the penis is indicated by the division of the cavernous veins into smaller channels prior to joining the subtunical venous plexus. Erectile tissue in the bifid origins of the corpus spongiosum has abundant cavernous muscle, while in the remainder of the corpus spongiosum little smooth muscle lines the cavernous spaces. The cavernous spaces on either side of the urethra coalesce to form vessels, each of which communicates with cavernous spaces in the glans. In addition, a bypass of the glans is effected by communication of these vessels directly with the deep dorsal vein. The apparent absence of muscular pads in vessels of the spongiosum, the relative paucity of cavernous smooth muscle, and the ample venous drainage provided by the deep dorsal vein may account for the lack of a venous occlusive mechanism similar to that of the corpora cavernosa penis. PMID- 1759694 TI - Geographic distribution of xanthine oxidase, free radical scavengers, creatine kinase, and lactate dehydrogenase enzyme systems in rat heart and skeletal muscle. AB - The geographic distribution of the following enzyme systems is described in the rat heart (left and right ventricles) and in different skeletal muscles (soleus, plantaris, and red and white gastrocnemius): xanthine oxidase and dehydrogenase, creatine kinase isoenzymes, lactate dehydrogenase isoenzymes, and the free radical scavenger enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase. No substantial difference in enzyme activities was observed between the left and right ventricles. Skeletal muscles showed a clear distinction between enzyme activities depending on their composition of oxidative fibers and glycolytic fibers. PMID- 1759695 TI - Learning to reproduce a list and memory for the learning. AB - The ability to reproduce from memory a short list of verbal items immediately following presentation is known to improve over successive trials on that list, even if these trials are embedded in a sequence of trials on other lists of the same sort (Hebb, 1961). Less clear is whether this "Hebb effect" arises without the list repetition being noticed. This question has long been pondered and has recently taken on particular theoretical significance, but the available evidence is scant and inconsistent. Two experiments are described in which, in essence, a sequence of immediate reproduction trials was followed by tests that called for list recognition (Experiments 1 and 2) and/or estimates of list presentation frequency (Experiment 1). These tests provided quantitative measures of repetition awareness. Typical Hebb effects were found, but there was no evidence that the effects occurred without the subjects' being aware of the repetition; effect-size analyses indicated that both the recognition and frequency responses were more sensitive to repetition than were the reproduction responses. Therefore, not only could the recognition and frequency responses not have been made solely on the basis of how readily the test lists were reproduced, but the Hebb effect could have required an awareness of repetition. PMID- 1759696 TI - Cognitive aspects of mental activity during sleep. AB - Upon nighttime experimental awakening of 27 subjects in four sleep conditions (sleep onset early; sleep onset late; Stage 2; and rapid eye movement, REM, sleep), 108 dream reports and their association reports were collected. Dream reports were analyzed for length (temporal units) and content categories (continuity; implausibility; presence of the dreamer [i.e., "the self"], a setting, characters). Associations were classified as episodic, abstract self referred, and semantic memories. The two sets of results tend to show a basic homogeneity among mentation reports in the four sleep conditions considered. These findings are interpreted as supporting the hypothesis that the same cognitive mechanisms operate, at different levels of engagement, in dream generation rather than the hypothesis of multiple dream-generation systems dependent upon the physiological characteristics of the various sleep stages. PMID- 1759697 TI - An auditory cue-depreciation effect. AB - An experiment is reported in which subjects first heard a list of words and then tried to identify these same words from degraded utterances. Paralleling previous findings in the visual modality, the probability of identifying a given utterance was reduced when the utterance was immediately preceded by other, more degraded, utterances of the same word. A second experiment replicated this "cue depreciation effect" and in addition found the effect to be weakened, if not eliminated, when the target word was not included in the initial list or when the test was delayed by two days. PMID- 1759698 TI - [Celiac plexus block: value of x-ray computed guidance]. AB - Celiac plexus block is a good alternative of pain treatment in upper abdominal pain. Neurolysis of the celiac plexus by the percutaneous posterior route used CT guidance in 8 patients. Pain relief was obtained in 5 of 7 patients (70 per cent); no complication occurred. PMID- 1759699 TI - [Diagnostic epidural analgesia in patients with chronic pain]. PMID- 1759700 TI - [Perineal pain and involvement of the internal pudendal nerves]. AB - A number of chronic pain syndromes in the perineal area can be related to pudental nerves suffering. The constancy of symptoms among various patients, and in duration for a particular one, alterations revealed by electrophysiologic studies, pain relief by diagnostic blocks, data from anatomic studies, preliminary results of medical and surgical applied therapies, give consistent arguments for possible organic lesions of pudental nerves. PMID- 1759701 TI - Prolonged stellate block in treatment of reflex sympathetic dystrophy. AB - Prolonged continuous stellate ganglion blockade has been found useful in treatment of post-traumatic reflex sympathetic dystrophy under the following circumstances: 1) When conservative treatment with outpatient physical therapy, tranquilizers and mild analgesics has failed. 2) When conservative therapy plus intermittent stellate blocks (q.l to 4 weeks) has failed. A three-year average follow-up of a group of 26 unselected patients has shown 25% relapse rate and 75% marked to complete improvement. PMID- 1759702 TI - [Sympathetic nervous system, pain and epidural administration of morphine]. AB - There are multilevel intrications between nociceptive afferences and sympathetic efferences: anatomical vicinity in visceral innervation; systemic and local activation of the sympathetic efferences in response to nociceptive stimulation; major role of sympathetic activation in the perpetuation of sympathetic dystrophies. The analysis of a retrospective series of 10 patients suffering from algodystrophia revealed that epidural morphine administration had a beneficial effect only in those which were treated at an early stage of their illness. Despite epidural morphine has been claimed to be without effect on the efferent sympathetic tone in normal animals and individuals, it seems that in some pathologic states, the sympathetic output can be depressed. Recent anatomical and neurophysiological evidences argue for such a possibility. PMID- 1759703 TI - [Management of pain in the home]. AB - Since patients treated with analgesics at home exist in ever-increasing numbers, and nurses are convinced of the efficacity of the treatment of pain, we are confronted with an urgent need for competent training. This is why, for a little over a year now, nurses have benefitted from theoretical and practical aids, allowing them to work more effectively, be it on the educative, therapeutic, technical and human level, so that patients benefit from a better quality of life and die in comfort and dignity. PMID- 1759704 TI - Hydrodynamic relaxation in flow field-flow fractionation using both split and frit inlets. AB - Two means are described for achieving hydrodynamic relaxation and thus avoiding the stopflow injection procedure in field-flow fractionation (FFF): split flow injection and frit inlet injection. The advantages, disadvantages, and the theoretical basis of these procedures are discussed. Incremental band broadening due to the final relaxation step is examined theoretically and shown to be negligible when the flow rate of the sample inlet substream is small compared to the total channel flow rate. The optimization of the sample inlet flow rate is discussed. Experimental results for both injection procedures are reported for flow/steric (or hyperlayer) FFF applied to latex standards, confirming the expected trends. However, closer examination shows that the observed incremental band broadening associated with hydrodynamic relaxation is somewhat larger than the value predicted. PMID- 1759705 TI - Surfactant-intercalated clay films for electrochemical catalysis. Reduction of trichloroacetic acid. AB - Composite films made from insoluble dialkyldimethylammonium surfactants and clay colloids were evaluated for electrochemical catalysis. When cast on pyrolytic graphite (PG) electrodes from chloroform, the films act as charge-transfer barriers toward multivalent electroactive ions in solution. They take up ions with hydrophobic ligands, e.g. tris-(2,2'-bipyridyl)cobalt(II). To make catalytic electrodes, water-insoluble cobalt and iron phthalocyanines (CoPc and FePc) were dissolved in surfactant-clay dispersions in chloroform and cast on PG. Films containing CoPc were 35-fold more active than FePc films for catalytic reduction of trichloroacetic acid. CoPc films decreased overpotential for reduction of trichloroacetic acid by about 0.5 V compared to 0.05 V for FePc. These MPc films gave stable catalytic currents for at least 10 days. Catalytic current vs temperature plots for reduction of trichloroacetic acid showed linear branches with intersection points close to reported gel-to-liquid crystal-phase transition temperatures. Charge transport was faster in the liquid crystal than the gel phase of the films. Observation of phase transitions suggests a multibilayer structure. PMID- 1759706 TI - Pulsed rapid heating method for volatilization of biological molecules in multiphoton ionization mass spectrometry. PMID- 1759707 TI - Determination of aluminum in the human serum of a dialysis patient by ion-pair reversed-phase partition high-performance liquid chromatography. AB - An ion-pair reversed-phase partition high-performance liquid chromatography spectrophotometric method is described for the determination of aluminum in human serum, based on its complexation with 2,2'-dihydroxyazobenzene. The chelate is separated on C18-bonded silica packing by using an aqueous methanol mobile phase containing tetrabutylammonium bromide and is detected with 0.005 AU full-scale at 510 nm. The proposed system offers a simple, sensitive, and selective method. The detection limits defined as twice the standard deviation of the blank signal, are 0.2 micrograms L-1 in pure solution and 6 micrograms L-1 in serum. The sample solution is prepared from 0.4 mL of serum after protein precipitation with hydrochloric acid and methanol. There was good agreement between the values obtained by this method and graphite furnace atomic absorption spectrophotometry. The aluminum concentrations in 121 patients on hemodialysis were 6-201 micrograms L-1. PMID- 1759708 TI - Collection efficiency of various solid-phase traps for off-line supercritical fluid extraction. AB - Solid-phase extraction tubes were evaluated as traps for off-line supercritical fluid extraction. Normal- and reversed-phase traps were studied with hydrocarbons, phenols, and a "test mixture" in order to determine the trapping efficiency. These traps were then used for the extraction of PCBs from river sediment. Polyethylene frits were also investigated for their use as solid-phase traps in SFE. PMID- 1759709 TI - Trace element determinations using a 15-keV synchrotron X-ray microprobe. AB - At the Synchrotron Radiation Source (SRS), Daresbury, U.K., a synchrotron microprobe was constructed, in order to create an instrument capable of analyzing at the ppm or in favorite cases sub-ppm level with a lateral resolution of 10 x 15 microns2. In order to span a wide range of elements to be analyzed, a beam energy of 15 keV was chosen. Focusing and monochromation of the white beam was done in one single step with a high-precision ellipsoidally concave curved Si(111) crystal. Sufficient flux of X-rays in a narrow energy band is available in the spot to measure trace elements at the femtogram level. Measurements on standard materials, reference standard materials, and biological samples showed the lower relative minimum detection limits and higher sensitivity for the higher Z-elements obtainable with micro-SXRF (synchrotron X-ray fluorescence) as compared with microtechniques using ion accelerators. Moreover, the much lower energy deposited in the specimen represents a major argument to prefer X-rays to ions for the analysis of radiation-sensitive samples. PMID- 1759710 TI - Selective biocoulometry of vitamin C using dithiothreithol, N-ethylmaleimide, and ascorbate oxidase. PMID- 1759711 TI - Amperometric glucose microelectrodes prepared through immobilization of glucose oxidase in redox hydrogels. AB - Glucose microelectrodes have been formed with glucose oxidase immobilized in poly[(vinylpyridine)Os(bipyridine)2Cl] derivative-based redox hydrogels on beveled carbon-fiber microdisk (7 microns diameter) electrodes. In the resulting microelectrode, the steady-state glucose electrooxidation current density is 0.3 mA cm-2 and the sensitivity is 20 mA cm-2 M-1. The current density and sensitivity are 10 times higher than in macroelectrodes made with the same hydrogel. Furthermore, the current is less affected by a change in the partial pressure of oxygen. The higher current density and lower oxygen sensitivity point to the efficient collection of electrons through their diffusion in the redox hydrogel to the electrode surface. These results contrast with those observed for enzyme electrodes based on diffusing mediators, where loss of the enzyme-reduced mediator by radial diffusion to the solution decreases the current densities of microelectrodes relative to similar macroelectrodes. PMID- 1759712 TI - Borate interference in surface-enhanced Raman spectroscopy of amines. AB - Interference from borate is observed in surface-enhanced Raman (SER) spectra of lysine and propylamine obtained with borohydride-reduced silver colloids. Borate bands are also observed in the spectra of other basic analytes, as well as when certain variations are made in the silver colloid preparation. The relative intensities of the analyte and borate bands depend on the pH of the colloid, the extent of oxidation of the colloid surface, and the relative adsorptivities of the analyte and borate. Benzylamine adsorbs more readily than propylamine and also competes more effectively with borate for adsorption sites. On the other hand, borate virtually excludes lysine from the surface when the solution pH is greater than or equal to 8. The formation of silver oxide in basified colloids may facilitate borate adsorption. For some basic analytes, eliminating the adsorption of borate ion and the resulting spectral interference may require using alternative SERS substrates. PMID- 1759713 TI - Cobalt(II)-catalyzed chemiluminescence in a dioctadecyldimethylammonium chloride bilayer membranous medium for the flow injection determination of phenylpyruvic acid. AB - A novel chemiluminescence system is described for the flow injection determination of phenylpyruvic acid (PPA). The presence of both ordered surfactant molecular assemblies and a metal ion catalyst in the system is essential for the phosphorescence of benzaldehyde (emitter) produced by the aerobic oxidation of PPA in alkaline solution. Dioctadecyldimethylammonium chloride bilayer aggregates and cobalt (II) allows PPA to be selectively determined down to 1 X 10(-7) M. The linearity is 2 orders of magnitude with a relative standard deviation 3.1% (n = 10) for 1 X 10(-6) M PPA. Of 28 other species (1 X 10(-3) M) tested, only 4-hydroxymanderic acid, 4 hydroxyphenylpyruvic acid, 2,5-dihydroxyphenylacetic acid, and 4-hydroxy-3 methoxyphenylpyruvic acid provided signals 2-13 times more intense than that for 1 X 10(-6) M PPA. PPA present at 10(-3) - 10(-2) M levels in urine from patients with phenylketonuria can be determined with no special sample pretreatment by using this CL procedure. The mechanistic study of the present luminescent reaction are also undertaken in detail. The bilayer aggregates were found to contribute favorably both to the production of key intermediates and to the efficient phosphorescence emission. PMID- 1759714 TI - Determination of site-specific carbon isotope ratios at natural abundance by carbon-13 nuclear magnetic resonance spectroscopy. AB - Site-specific natural isotope fractionation of hydrogen studied by deuterium NMR (SNIF-NMR) spectroscopy is a powerful source of information on hydrogen pathways occurring in biosyntheses in natural conditions. The potential of the carbon counterpart of this method has been investigated and compared. Three typical molecular species, ethanol, acetic acid, and vanillin, have been considered. Taking into account the requirements of quantitative 13C NMR, appropriate experimental procedures have been defined and the repeatability and reproducibility of the isotope ratio determinations have been checked in different conditions. It is shown that the carbon version of the SNIF-NMR method is capable of detecting small differences in the carbon-13 content of the ethyl fragment of ethanols from different botanical or synthetic origins. These results are in agreement with mass spectrometry determinations of the overall carbon isotope ratios. Deviations with respect to a statistical distribution of 13C have been detected in the case of acetic acid and vanillin. However, since the method is very sensitive to several kinds of systematic error, only a relative significance can be attached at present to the internal parameters directly accessible. Isotope dilution experiments have also been carried out in order to check the consistency of the results. In the present state of experimental accuracy, the 13C NMR method is of more limited potential than 2H SNIF-NMR spectroscopy. However it may provide complementary information. Moreover it is particularly efficient for detecting and quantifying adulterations that aim to mimic the overall carbon-13 content of a natural compound by adding a selectivity enriched species to a less expensive substrate from a different origin. PMID- 1759715 TI - Fourier transform infrared spectroscopic method for the quantitative trace analysis of transition-metal carbonyl-labeled bioligands. AB - A quantitative FT-IR spectroscopic method has been developed for the trace analysis in chlorinated organic solvents of transition-metal carbonyl-labeled bioligands. In order to illustrate the widespread analytical potential of the method, three derivatives of the female hormonal steroid 17 beta-estradiol, containing Cr(CO)3, Cp2Mo2(CO)4 (Cp = eta 5-C5H5), and Co2(CO)6 as labels, and the anticonvulsant drug phenobarbital, labeled with (eta 5-C5H4)Mn(CO)3, were examined. The cobalt carbonyl marker proved to be the best sulted for quantitative analysis purposes, and the minimum tracer quantity detectable for this particular marker (64 scans, 4-cm-1 resolution, 3.5 min) was optimized in CCl4 solution at about 300 fmol (or 0.3 pmol, 180 pg) by using an ultralow volume (23.0 microL), gold light-pipe IR solution cell and a liquid nitrogen cooled, InSb (indium antimonide) IR detector. The repeatability of this radically different analytical procedure over the concentration range 1.0 x 10(-6) to 5.0 x 10(-8) M was good (coefficient of variance less than or equal to 6%) and the method provides the basis for a new immunological test- carbonylmetalloimmunoassay (CMIA). PMID- 1759716 TI - Integrated fluid handling system for biomolecular interaction analysis. AB - An integrated fluid handling system used for multichannel biomolecular interaction analysis is described. Reactions between biological molecules are monitored in real time by measuring changes in the angular position where surface plasmon resonance occurs at a biospecific active surface. The adsorption efficiency of the analyte onto the biospecific active surface is up to approximately 3%, due to the low channel height, 50 microns, in the flow cell. When a large part of the total biospecific active surface for surface plasmon resonance probing (approximately 0.15 mm2) is used, the sensitivity is high. Sample sizes in the order of 1-50 microL can be injected. The sample zone dispersion is minimized by the low dead volume in the system (approximately 0.4 microL) accomplished by using integrated sample loops and thin conduits. An asset of this integration is the low reagent consumption. The sensor chip with the biospecific active surface is reusable and easily exchanged. Experimental results obtained with a theophylline monoclonal antibody as the analyte are compared with a theoretical model. The standard deviation for the repeatability is approximately 5% typically with 50 microL of 250 pM analyte, and the assay time is 10 min. The detection limit is approximately 10 pg of the analyte on the probed spot of the surface. Possible improvements of the sensitivity and detection limit are discussed. PMID- 1759717 TI - Amperometric detection of alcohol in beer using a flow cell and immobilized alcohol dehydrogenase. PMID- 1759718 TI - On-line immunoaffinity sample pre-treatment for column liquid chromatography: evaluation of desorption techniques and operating conditions using an anti estrogen immuno-precolumn as a model system. AB - An immunoaffinity precolumn (immuno-precolumn) containing an immobilized antibody directed against estrogen steroids, was used as a model system for the evaluation of different desorbing techniques, suitable for on-line coupling to column liquid chromatography (LC). Desorption of estrogen analytes from the immuno-precolumn proved to be impossible with the buffers and chaotropic solutions frequently used in affinity desorption. Micellar solutions are effective in obstructing the antibody-antigen reaction, but their use as desorbing solutions was not found to be practical because of the large interferences introduced into the chromatograms. Desorption with aqueous solutions at elevated temperature, created by microwave action or conventional heating, although effective is not practical in this instance, because the agarose used in this study as the stationary phase for the immuno-precolumn is prone to heat decomposition. The most effective and practical approach is desorption with a methanol-water mixture (95 + 5 v/v). On line dilution of the eluate allows the concentration of the desorbed analytes using a reversed-phase LC system with subsequent separation and ultraviolet detection. The performance of the system with spiked urine and plasma samples, which were introduced directly into the system, was evaluated and the results were compared with immunoselective desorption. PMID- 1759719 TI - Simultaneous determination of toxic metabolites by linear combination derivative spectrophotometry. AB - A linear combination derivative spectrophotometric method is described. The method overcomes the problem of overlapping in derivative spectrophotometry and allows the maximum use of quantitative information. In addition, the method can be used to increase the selectivity, sensitivity and accuracy of the simultaneous analysis of multicomponent mixtures. The application of the method to the simultaneous determination of bongkrekic acid and toxoflavin, the toxic metabolites produced by Pseudomonas farinofermentans, is described. PMID- 1759720 TI - Amperometric monitoring of bacteria-induced milk acidity using a platinum disc microelectrode. AB - The acidity induced by the action of bacteria in milk samples was monitored amperometrically by using a platinum microelectrode. The measurements were performed directly on commercial packs of milk, stored at 32 degrees C, and were continued for 9-10 d after inoculation. The data were compared with those obtained by measuring the pH of the samples and the results are discussed on the basis of the metabolism of each bacterial species. The effects of the following bacteria were examined: Staphylococcus aureus, Bacillus cereus, Streptococcus faecalis, Bacillus subtilis, Aeromonas, and Corynebacterium. PMID- 1759721 TI - [The structure of the bovine mammary gland during the dry period with special reference to the process of involution. 2. Electron microscopic studies]. AB - According to the electron microscopic investigations the most evident sign of the phase of the active involution of the mammary gland in cattle is the occurrence of different great vacuoles with a diffuse content in the cytoplasma of the secretory cells till the 30th day after the beginning of the dry period. Secretory cells which go over in the rest phase show a great reduction of the cell organelles and many filaments and secondary lysosomes or residual bodies. One can observe many macrophages and lymphocytes in the partly enlarged intercellular rooms between the secretory cells and the myoepithelial cells. The myoepithelial cells are adapting to the changing forms of alveoli. The phase of the colostrogenesis is characterised by the enlargement of the cell organelles and the reappearance of vacuoles. PMID- 1759722 TI - Spinal root origin of the radial nerve and nerves innervating shoulder muscles of the dog. AB - The ventral spinal root origin of the radial nerve, its muscle branches, and brachial plexus nerves which supply shoulder and thoracic musculature was determined in the dog. Electrophysiological signal averaging techniques measured evoked potential from specific ventral spinal roots to individual muscle nerves. The entire radial nerve received input from the sixth cervical (C6) through the second thoracic (T2) spinal roots. The most significant (p less than .05) input to triceps brachii came from C8 while the deep ramus of the radial nerve received its largest input from C7. The brachiocephalicus, suprascapular, and subscapular nerves all received their most significant (p less than .05) innervation from C6. Approximately 90% of the evoked potential to the axillary nerve originated from C7. The thoracodorsal nerve received most of its innervation from ventral roots C7 and C8. The lateral thoracic nerve which innervates the cutaneous trunci muscle was supplied by ventral roots C8-T2. Examination of innervation patterns suggests that only modest variation of spinal root input to specific nerves occurred between individual dogs. PMID- 1759723 TI - The os coxae of a digging form of the northern water vole, Arvicola terrestris (Rodentia, Arvicolidae). AB - Data on the morphology, relative growth and sexual dimorphism of the os coxae of a digging form of the northern water vole Arvicola terrestris (A.t. monticola) are given. Two hundred ninety-nine specimens (146 males and 153 females) caught in the Aran Valley (Spanish Pyrenees) were analyzed. The specimens were distributed into six classes of relative age, according to the skull morphology, kind of coat, moulting state, weight and sexual state. The morphological features of the os coxae in these specimens are similar to those described in other species of Arvicolidae. The hormonal effect upon the pelvis in adult females during pregnancy and parturition leads to the appearance of marked intersexual differences in the obturator foramen length, the pubis length, the pelvis length and, specially, in the pelvis height and the pubis width. By means of Becker's and Dunmire's procedures both sexes can be correctly discriminated in a 78.87 and a 76.4% respectively. Conjugating the variation patterns obtained with Becker's index and the pelvis height, we have obtained a more effective method of sexual differentiation (an 85.51% of correct discrimination). PMID- 1759724 TI - Scanning electron microscopic observations on the development and structure of tooth enamel in Cervidae (Mammalia: Ruminantia). AB - Enamel formation and structure were investigated in 102 developing or erupted teeth of roe, fallow and red deer. Special attention was given to the topography of the forming enamel surface, the form, arrangement and course of enamel rods, its relation to interprismatic enamel and the occurrence of Hunter-Schreger-bands in the enamel. Discussed are the significance of the enamel pattern for the identification of certain taxa and the adaptive value of Cervidean enamel structures. PMID- 1759725 TI - Dural sinuses in the camel and their extracranial venous connections. AB - The dural sinuses of one-humped camel (Camelus dromedarius) and their connections with veins of the head and neck were described and, whenever possible, were compared with other domestic animals emphasizing species differences. Information obtained from gross dissection of embalmed camel heads was correlated with latex injected vascular casts, as well as venographs. Although the disposition of the dural sinuses, in general, was similar to those of other domestic animals, they were somewhat complex in the camel. An important venous flow mechanism which functions in the thermoregulation of the brain in the camel was described. The venous drainage of the nasal cavity and its surrounding areas had five connections with the ophthalmic plexus and the cavernous sinus: (1) the infraorbital vein----ophthalmic plexus; (2) the medial superior palpebral vein--- ophthalmic plexus; (3) the medial inferior palpebral vein----ophthalmic plexus; (4) the angularis oculi----frontal----supraorbital----dorsal external ophthalmic- --emissary vein of the foramen orbitorotundum----cavernous sinus; and (5) the deep facial vein----ventral external ophthalmic----emissary vein of the foramen orbitorotundum----cavernous sinus. PMID- 1759726 TI - [The wisdom of the animal body]. AB - In 1932 CANNON described the physiological wisdom of the body. This cannot exist without morphological wisdom. Since morphology is a formative process, both kinds of wisdom depend on the same formative forces. These forces are the forces of consciousness at all levels. Their existence is proved by the fact that they can be eliminated by narcosis. The wisdom of these forces is twofold: Firstly, the wisdom of need sensation which lasts only until the need is satisfied. This is the conscious intelligence of the body which is responsible for restraint in all living beings. Secondly, the wisdom, or better, the prudence of need satisfaction which requires knowledge and appropriate tools. The organs of the body are these tools. Knowledge belongs to the intellect which knows how to handle material. This is achieved in all prehuman species subconsciously and is demonstrated in all structures built by cells and animals. Only the human mind can be unwise and imprudent; but man, being free, is also able to be wise and prudent and so prevent the extinction of the earthly creation. PMID- 1759727 TI - [Immunosuppressive drugs and autoimmune diseases]. AB - Only a few immunosuppressive drugs can be used today. These are: corticosteroids, azathioprine, cyclophosphamide, ciclosporine A, accessorily chlorambucil and methotrexate. They all have different actions on immune responses. The use of these drugs has completely changed the prognosis of autoimmune diseases such as systematic lupus erythematous, polyartheritis nodosa, Wegener's granulomatosis. Nevertheless treatment of other autoimmune diseases, such as type I insulin dependent diabetes mellitus or multiple sclerosis, has been inconclusive. PMID- 1759728 TI - Oral ecology and its pathogenic relation with the origin of primary periodontitis associated with plaque. AB - Microbial factors involved in the genesis of periodontitis are related with supragingival (coronal) and subgingival plaque. The microorganisms in the supragingival plaque reach the gingival sulcus, and are influenced by ecological determinants in this zone which condition the establishment of adherent plaque. This plaque may subsequently form the substrate for particularly periodon to pathogenic bacteria, which may then form plaques adhered to the epithelium, or develop as floating (nonadhered) populations. After microbial colonization of the gingival sulcus, bacteria or substances they produce may reach the junctional epithelium and alveolar bone, leading to direct tissular destruction to an extent determined by the host's immune response. Damage may be local or generalized, depending on additional factors. PMID- 1759729 TI - [Multicenter study on purified protein C concentrates and defined plasma levels]. AB - A variety of protein C assays are available as commercial kits. A collaborative study was undertaken to evaluate the performance of protein C assays. Various samples including calibrated plasmas and high purity concentrates destined to therapy were distributed among five laboratories. This comparison of protein C assays indicates that protein C levels measured by different functional or immunological assays and by five laboratories are very close for calibrated plasmas but not for high purity concentrates. The selection of the standard and the dilution buffer for protein C concentrates have important implications for the interpretation of the results. Dilution of purified protein C concentrates in protein C deficient plasma which restaure a total protein level similar to that of normal plasma improve the accuracy of functional protein C assays. PMID- 1759730 TI - Detection of Mycoplasma hominis antibodies by three different techniques, application to women with pelvic inflammatory disease. AB - Mycoplasma hominis, a mycoplasma potentially isolated from the genital tract of healthy women, seems to have some role in pelvic inflammatory diseases (PID). Three serologic techniques were developed to detect antibodies to M. hominis: ELISA (IgG, IgM), microimmunofluorescence (MIF) and Western blot. Rabbit and human control sera were used to establish the standard assay conditions. ELISA proved to be more sensitive but less specific than MIF. Cross-reactivity with antibodies to M. pneumoniae existed with ELISA but not with MIF. Twenty six and 60 kDa proteins were responsible for that cross-reactivity, as assessed by Western blot analysis. Among 33 patients with PID, 18 to 35 year old, 67% had antibodies to M. hominis by ELISA and 33% by MIF. Among 52 age comparable healthy women, 44 and 13% were positive for M. hominis by ELISA and MIF respectively. The Western blot analysis showed heterogeneity in the antibody response to M. hominis, but a 76 kDa protein reacted with half of the tested sera. Our study agrees with some role for M. hominis in PID. M. hominis was certainly the primary pathogen in one case, played a role that was probable in seven cases, and possible in three patients. PMID- 1759731 TI - [Glycoforms of serum alpha 1-antichymotrypsin studied by immunoaffino electrophoresis. From the fundamental aspect to clinical applications]. AB - alpha 1-antichymotrypsin, purified or in whole serum, exhibits microheterogeneous forms when studied by crossed immunoaffinoelectrophoresis with free concanavalin A (Con A) in the first dimension. alpha 1-antichymotrypsin purified from the serum of a single healthy donor was separated into three forms by affinity chromatography on a Con A-Sepharose 4B column: a Con A non-reactive form, a Con A weakly reactive form and a Con A reactive form. Some of their physico-chemical properties are compared. The complete primary structure of the glycans of each form was determined by high resolution 1H-NMR spectroscopy. The results indicated the presence of diantennary and triantennary type glycanic structures which occur frequently in serum glycoproteins. From deglycosylation experiments it is concluded that alpha 1-antichymotrypsin carries four oligosaccharide side chains. The Con A non-reactive form contains four triantennary glycans, the weakly reactive form contains three triantennary and one diantennary glycans and the Con A reactive form possesses on average one triantennary and three diantennary glycans. Significant variations in the relative ratios of the microheterogeneous forms were detected in various inflammatory syndromes. There is an increased proportion of Con A non-reactive form in patients developing a systemic disease (systemic lupus erythematosus, rheumatoid arthritis, temporal arteritis). In contrast, the proportion of Con A non-reactive form decreased in patients with acute septic inflammation whereas no variation appeared in patients with metastatic breast cancer. We also studied the variations of alpha 1 antichymotrypsin microheterogeneity in sera from patients with giant-cell arteritis and/or polymyalgia rheumatica before and during treatment with glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759732 TI - [Multicenter study of 435 yeast strains isolated from 116,000 hemocultures]. AB - During a multicentric study on the diagnosis of yeast septicemia, 5 blood culture media have been compared. 435 yeast strains have been isolated from 116,372 blood cultures received during year 1989 in the mycological laboratories of 5 university hospitals from east of France. The results show that Candida albicans is always the first septicemia agent with 52% of yeasts isolation from blood. C. parapsilosis comes next with 17%, then C. glabrata, 6.2%. The average delay of yeasts isolation is 2.3 days for Bactec NR and Sabouraud media, 3.7 days for other bacteriological media. Compared with polyvalent media, Sabouraud diphasic medium is significantly the best for yeasts isolation. It is recommended to add chloramphenicol in the medium, to culture 10 ml of blood and to keep blood cultures for at least 8 days, better 15 days. PMID- 1759733 TI - [Epidemiology and prevention of mental disorders]. AB - From a bibliographic analysis and personal experiences, the authors present the advantages of the epidemiologic method in psychiatry. They point out its specificity and the methodological difficulties. Since the psychiatric practices are being deeply transformed, it becomes essential to know precisely the importance and the distribution of mental diseases in the population. It is not possible to image changing a care system trend without knowing the real needs of the population. The descriptive epidemiologic method contributes to this. The aim of analytic epidemiology is ever more important since it allows to spot the circumstances in which mental diseases appear and are developed, and to elaborate etiological hypotheses. Finally, this favors preventive approaches where evaluative epidemiology permits to measure the validity and effectiveness of programs which, like those elaborated for other social calamities (transmissible diseases, degenerative diseases), take place for studies in the field of mental health disorders. PMID- 1759734 TI - [Nosological classifications of obsessive-compulsive disorder]. AB - Obsessive-Compulsive Disorder (O.C.D.) has become of central interest to researchers. Conflicting data in neurobiological studies and the diversity of the responses to behavioral and pharmacological treatments, have raised the question of the homogeneity of O.C.D. Is O.C.D. an heterogeneous diagnosis? Is it one or several disorders? if so, how can it be divided into homogeneous subgroups? What is the meaning of psychiatric comorbidity with regard to a neuropharmacological approach of O.C.D.? Has O.C.D. a large spectrum, which includes other disorders like Gilles de la Tourette syndrome, trichotillomania, paraphilia, compulsive gambling and other impulse control disorders? Many classifications are established within O.C.D. in an attempt to delineate similarities and differences among clinical manifestations and to develop more adequate and effective treatments. Based on recent literature data and on the experience we have accumulated in assessing and treating people presenting O.C.D., we propose a new clinical classification of this disorder. PMID- 1759735 TI - [Language disorders in schizophrenia]. AB - Psychiatrists, psycholinguists and linguists have been interested in the language disorders of schizophrenia. Physicians have described their semiology. Psycholinguists have tried to show their structural alterations, using standardized tests in the fields of syntax, semantics and more recently, prosody. We try to present Benveniste's and Culioli's Enunciation Theory and Irigaray's works. Only a theory which studies the dynamic aspects of language would be of some use for the analysis of schizophrenic language. PMID- 1759736 TI - [Indications of lithium plasma levels in professional practice. Average of a 7 year follow-up]. AB - With a mean follow-up duration of 7 years, the retrospective analysis of 57 charts of lithiotherapy shows that: Better results are observed when the lithium blood level reactus 0.87 mmoles/l. In that case, the best lithiotherapy indication is the major recurrent long cycles depression. We also propose as lithiotherapy indication in order of efficacy: 1--The maniac-depressive psychosis (P.M.D.) in its mixed form. 2--The schizo-affective troubles. The curative and preventive lithium efficacy is on favour of the diagnosis of recurrent endogenous psychiatric disease. PMID- 1759737 TI - [Analysis of dermatoglyphics in a population of female psychiatric patients]. PMID- 1759738 TI - [Commitment of the psychiatrist in general and in legal psychiatry]. PMID- 1759739 TI - [Mystical delusion: a disease of faith?]. PMID- 1759740 TI - [Diagnostic strategy of acoustic neuroma. Evaluation of efficacy of auditory evoked potentials. Apropos of a series of 50 neuroma cases]. AB - The authors carry out a retrospective study of the diagnostic procedures used in a series of 50 acoustic neuromas. AEP were performed for thirty-four neuromas at some stage of their history. The findings were perfectly normal for eight of them, which represents a sensitivity level of 76%. Various elements likely to account for this are put forward, then the role of AEP and MRI in the diagnostic strategy for neuroma is discussed in the light of this study. Finally, the authors emphasize the necessity to regularly evaluate the diagnostic methods in order to guarantee their quality and reliability. PMID- 1759741 TI - [Comparative study of temporal parameters of alaryngeal voices. Esophageal and tracheo-esophageal voices]. AB - Recent studies have established significant acoustic and phonetic differences between tracheo-oesophageal (TE) and conventional esophageal voices (EV). 12 alaryngeal voices (2 esophageal, 6 myomucosal shunts, 4 tracheoesophageal phonatory protheses), and 7 normal laryngeal voices were recorded and analyzed. Speech timing including voicing and pauses distribution was evaluated and compared to laryngeal voices. Speakers with TE voices using pulmonary air were able to preserve the rythm and the syntactico-semantic structure of their speeches, as opposed to speakers with EV who often had to insufflate air into the esophagus and therefore had a staccato-like speech. The phonation time was quite similar in both situations, but the length and the number of pauses made the difference. PMID- 1759742 TI - [Experimental endolymphatic hydrops. Biochemical data in the guinea pig]. AB - The electrochemical and osmotic composition of the inner ear fluids has been studied during experimental endolymphatic hydrops in guinea pig. The data showed that the modifications of the electrochemical composition of endolymph has been detected only after more than 2 weeks after the hydrops induction. The endocochlear potential, the K and Cl concentrations, and the osmolality progressively decreased between 6 and 9 weeks of hydrops. The longitudinal gradients disappeared. After 24 weeks of hydrops, the endocochlear potential was 50% of the initial value whereas the K and Cl concentrations and the osmolality were higher than that measured at 9 weeks but remained lower than contralateral, normal values. These results suggest that the alterations of the electrochemical and osmotic composition of endolymph that were observed during the evolution of experimental endolymphatic hydrops in guinea pig are related to an alteration of the permeabilities of the Reissner's membrane induced by an increase of hydrostatic pressure. PMID- 1759743 TI - [Olfactory mucosa and Alzheimer's disease. Technique for biopsy and ultrastructural study]. AB - The discovery of a reliable peripheral marker would be of a great interest for the early diagnosis of the Alzheimer's Disease. The olfactory deficit and the major histologic changes of the olfactory-related areas of the brain occurring during this disease raised the possibility that the olfactory epithelia could be one of the way of entry of a possible process that still has to be identified. We have developed an instrument and a technique of biopsy of the human olfactory mucosa to search for the presence of characteristics lesions on patients suffering of an Alzheimer's Disease. These small specimens have been prepared for electronic microscopy. The ultrastructural study of a sample of olfactory mucosa has been realised in 9 cases (5 Alzheimer's-4 controls) revealing in 4 patients suspected of an Alzheimer's Disease a complete architectural disorganisation with a destruction of the dendrite of the olfactory cells and a severe degeneration of the sustentacular cells. We did not find any characteristic changes such as Paired Helicoidal Filaments or amyloid fibrils. These results do not presuppose of their eventual presence at a precocious stage of the disease. Further ultrastructural and immunochemical studies carried out with patients at various stages of the disease are necessary in order to confirm this hypothesis. PMID- 1759744 TI - [Pseudotumoral salivary localization of Destombes-Rosai-Dorfman syndrome. Hemophagocytic histiocytosis. Diagnosed by bilateral submandibular and parotid involvement]. AB - We report one case of pseudotumoral salivary location of the Rosai-Dorfman syndrome, with a favorable outcome, occurring in a 32-year-old man from Guadeloupe. The clinical, biological and clinicopathological features of this syndrome, as well as the pathogenetic hypotheses, are summed up. In this case, no bacterial, fungal, parasitic or viral agent was discovered. The subject presented with no immune abnormality likely to account for the persistence and intensity of the histiocytic infiltration with lymphophagocytosis associated to the lymphoplasmocytic infiltration. The rarity of ENT, and more specifically salivary, locations is emphasized. The importance of the detection of possible immune abnormalities in such patients is demonstrated by the outcome of the syndrome being more often unfavorable when such abnormalities are present. PMID- 1759745 TI - [Combined approach to malignant tumors of the ethmoid and other paranasal sinuses. Principles and results]. AB - The authors present their experience concerning combined transfacial and neurosurgical procedures in the treatment of carcinomas of the ethmoid sinuses. 109 ethmoid-spheno-orbital tumors were treated at our department from 1982 to 1990: 85 were located into the ethmoidal and/or sphenoidal sinuses; 78 of these were malignant. Among the 65 ethmoidal carcinomas which were operated through a combined route, 48 underwent an induction chemotherapy and 19 a post-operative radiotherapy. The surgical technique is detailed, mostly the intra-cranial approach and the reconstruction of the cranial basis. Clinical results, and particularly the actuarial survival rates are discussed. The 5-year actuarial survival rate is 40% for all first hand ethmoidal adenocarcinomas. The figure reaches 52% for the patients without intra-cranial extension. At last, the 5-year actuarial survival rate is 100% for patients having a complete clinical response to induction chemotherapy. PMID- 1759746 TI - [Insufficiency of ethmoidectomy in the treatment of nasal polyposis]. AB - The authors report 100 ethmoidectomies performed on 50 patients between 01/87 and 09/89. 75% have been treated anteriorly by systemic corticosteroids. 65% have had prior sinus surgery. Follow-up time ranged from 12 to 34 months (mean: 18 months). A regular treatment with intranasal steroid sprays was taken post operatively by 96% of patients until three months and 48% until 18 months. 72% of patients considered the symptoms relief as satisfactorily (score of satisfaction greater than 8/10). Severe nasal obstruction, noted in 88% cases pre-operatively, reappeared in 26% 18 months post-operatively. Anosmia, encountered in 72% pre operatively, disappeared post-operatively in one half of the cases with a good conservation of olfaction 18 months later. Anterior and/or posterior rhinorrhea, sneezing were also satisfactorily controlled. Results on facial pain were not significant. Endoscopic evaluation was performed by a physician who was not the surgeon. A normoplastic mucosa covered the ethmoid cavities in 40%. Localized oedema was observed in 38%. An asymptomatic recurrence, discovered on endoscopic examination, was present in 11%. The symptomatic recurrence rate was 11%. A CTscan control, performed the day of the endoscopic examination and analysed few weeks later, reinforced the degree of objectivity. A complete marsupialization of the ethmoid labyrinth without any remaining cell was confirmed in only 30%. Frequence and aspects of the opacities in the great sinuses were the same pre- and post-operatively. So, this study shows that the insufficiencies of the ethmoidectomy are 1) the difficulty to perform a complete marsupialization of the ethmoid 2) persistent opacities in the great sinuses 3) persistence of the mucosa disease after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759747 TI - [Cholesteatoma of the paranasal sinuses. Apropos of 2 cases]. AB - Two cases of cholesteatoma of the facial sinuses are presented. One of them was located in the maxillary sinus and the other was originally located in the ethmoid cells and extended into the maxillary sinus. After reviewing the literature on this subject, the authors analyze the pathogenetic theories and the clinicoradiological expressions. These raise an obvious diagnostic difficulty: the diagnosis is virtually impossible to establish before surgery and a clinicopathological study are performed. PMID- 1759748 TI - [Clinical polymorphism of lupus erythematosus]. PMID- 1759749 TI - [Lupus erythematosus and papules. 4 cases]. AB - Papular skin eruptions are uncommon in lupus erythematosus (LE), and their occurrence may suggest several diagnoses. We report four cases of papular eruptions in LE patients. Two of these patients had purely lupoid papules on acute LE in one and on chronic LE in the other. In the remaining two cases the papules were formed by mucinous deposits that were either secondary to LE or belonged to an associated primary mucinosis. These four cases prompted us to discuss the significance of papular eruptions in lupus erythematosus. LE-specific papular manifestations have a purely lupoid histological and immunopathological substratum. In systemic LE, the frequency of these manifestations varies from one series to another, but they seem to rank fourth after vespertilio, alopecia and photosensitivity. The papules vary in size and number, and they usually complicate a severe and active systemic LE. In chronic LE, a papulo-nodular eruption may be observed, but this is even rarer. Papules occurring in the course of LE may suggest a diagnosis of mucinosis, this disease being either secondary to, or associated with LE. Secondary mucinosis is intricated with LE-specific histological abnormalities. It appears as a symptomatic alcianophilic deposit induced by cytological alterations in some dysimmune collagen diseases, such as dermatomyositis or LE. In the literature, three cases of mucinosis secondary to LE are well documented, and to these we add a fourth case in which the papules contained lupoid lesions and a variable amount of dermal mucinous deposit. The literature has also yielded sixteen cases of primary papular mucinosis associated with systemic LE (12 cases) or chronic LE (4 cases); we add to these a case of systemic LE in which the papular eruptions varied in course, density and size of the papules. As in isolated papular mucinosis, histology regularly shows a copious mucinous deposit. When present, the LE-specific skin manifestations are clearly distinct from those of mucinosis (except for the above-mentioned cases of papular lupus). The course of papular mucinosis usually runs parallel to that of LE which is characterized by its severity and its articular, haematological and renal manifestations. Analysis of the literature also provides various anatomico clinical elements which help in differentiating between isolated papular mucinosis and primary papular mucinosis associated with LE. In the majority of cases treatment relies on corticosteroid therapy or synthetic antimalarial agents, but the results are irregular since LE seems to be more resistant to treatment than mucinosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1759750 TI - [Buccal and ocular localizations of pyoderma gangrenosum in Vaquez's disease]. PMID- 1759751 TI - [Multiple minute hyperkeratoses. Apropos of 2 cases]. PMID- 1759752 TI - [Vesiculobullous disseminated lupus erythematosus. Apropos of a case]. PMID- 1759753 TI - [Multiple recurrence of epithelioid sarcoma]. PMID- 1759754 TI - [Ocular complication disclosing juvenile xanthogranuloma. Apropos of a case]. PMID- 1759755 TI - [What is your diagnosis? Cervical lymphadenitis]. PMID- 1759756 TI - [Pharmacological or functional nevi. Cutaneous hamartoma caused by abnormal hormonal cell receptors]. PMID- 1759757 TI - [Management of pruritus in pregnancy]. PMID- 1759758 TI - [Treatment of keloids]. PMID- 1759759 TI - Non-steroidal anti-inflammatory drugs and stercoral perforation of the colon. AB - Within 6 months, three constipated patients have been seen with stercoral perforation of the colon associated with the ingestion of non-steroidal anti inflammatory drug medications (NSAIDs). These drugs were taken regularly for painful musculoskeletal disorders 6, 8 and 12 months before admission. Constipation is thought to be the most significant contributory factor in the development of colonic stercoral perforation; however, it is unclear why it develops in so few of the many patients with severe constipation. NSAID medications have been associated with the perforation of colonic diverticula, but there are no reports of an association with stercoral perforations. If our finding of the association is substantiated by other reports there may be a need for greater awareness of lower gastrointestinal problems when prescribing such drugs to constipated patients. PMID- 1759760 TI - Are current techniques of inguinal hernia repair optimal? A survey in the United Kingdom. AB - Data was collected on the techniques currently employed in adult inguinal hernia repair by means of a postal questionnaire to consultants in four Regional Health Authorities in England. Questionnaires were returned by 240 consultants (85%). This identified a considerable range in methods of repair, with a Moloney nylon darn being the sole method used by 35% of consultants, and the Shouldice technique, either alone or in combination with other methods, being used by 20%. Overall, 51% employ a subcuticular suture for skin closure, and traditional skin sutures are used by 31%. There was no association between consultant's date of qualification or subspecialty and type of repair. Consultants qualifying after 1969 are most likely to use a subcuticular suture. Some 14% of all consultants and 19% of those qualifying since 1969 employ a Shouldice procedure and a subcuticular suture. PMID- 1759761 TI - Dr Paul Tessier. PMID- 1759762 TI - Antibiotic prophylaxis in penetrating injuries of the chest. AB - Most prospective studies recommend antibiotic prophylaxis whilst a thoracostomy tube is in place or even longer. We conducted a randomised study of 188 patients with penetrating chest injuries requiring a chest drain. Of these patients, 95 received a single dose of ampicillin before insertion of the chest tube, the remaining 93 patients received additional antibiotic prophylaxis for as long as the drain was in place. The incidence of intrathoracic sepsis (pneumonia or empyema) was 3.1% and 3.2%, respectively. It is concluded that single-dose prophylaxis in penetrating chest trauma is as effective as prolonged prophylaxis. The importance of chest physiotherapy immediately after the drain insertion and of early removal of the drain is stressed. The role of various possible risk factors in the development of sepsis is discussed. PMID- 1759763 TI - Application of the laryngeal mask airway to thyroid surgery and the preservation of the recurrent laryngeal nerve. AB - We report our experience of using the laryngeal mask airway (LMA) in 13 consecutive patients undergoing thyroid surgery and discuss the advantages and limitations of the technique. We also describe a method, based on the use of the LMA, for identifying and preserving the recurrent laryngeal nerve during thyroid surgery. PMID- 1759764 TI - An objective long-term evaluation of the Angelchik antireflux prosthesis. AB - This paper reports the long-term results of the Angelchik antireflux prosthesis (ACP) in Nottingham from October 1981 to December 1989 in 42 patients with gastrooesophageal reflux disease (GORD). Pre- and postoperative oesophagoscopy, pH monitoring, acid reflux provocation test (ARPT), manometry and symptom evaluation were documented to assess the benefits of the procedure. There were no operative complications, dysphagia was the commonest postoperative problem and necessitated the removal of four ACPs. In most patients, dysphagia resolved within 1 year of surgery. Recurrence of reflux symptoms resulted in revision surgery in two patients. In general, reflux control was good. We believe that the ACP is a good antireflux operation which gives good long-term reflux and symptom control in the majority of patients. The removal rate of 15% in our series is of some concern but may be due in part to operator skills. The long-term objective follow-up has shown a trend towards a return of GOR and this and the unknown long term effects of implanted silicone may limit the use of this procedure to the more elderly patient. PMID- 1759765 TI - ERICA predicts response to tamoxifen in elderly women with breast cancer. AB - Oestrogen receptor status has been determined by an immunocytochemical assay using fine-needle aspiration samples of primary breast cancers in elderly patients. In a prospective study 56 patients were treated with tamoxifen only. Satisfactory assays were achieved in 49 patients. Disease was controlled by tamoxifen in 32 of 35 (91%) patients with oestrogen receptor positive tumours, compared with only 1 (7%) of 14 who were receptor negative. Immunocytochemical assay on fine-needle aspiration samples is relatively non-invasive and simple to perform, it accurately predicts response to tamoxifen in elderly patients and can be used to select patients for tamoxifen only therapy. PMID- 1759766 TI - Breast cancer data collection for surgical audit. AB - Data are available about the mortality, the incidence, the stage, the survival, and the treatment of breast cancer. In this country mortality data are published by the OPCS and HIPE and evidence exists to show that there is a considerable shortfall in both these sources. The incidence of breast cancer is recorded by the Regional Cancer Registries and published by OPCS. The registries supply OPCS with a minimum data set which does not include the stage of the disease, which is important, and does include the quadrant, which is not. Audit shows marked regional variations in completeness of registration. International comparisons with Scandinavia are unfavourable and show what can be achieved. Patients who develop breast cancer but do not die from it may be cured. The discrepancy between incidence and mortality, which varies both geographically and historically, should therefore provide a valuable insight into changing survival, but does not do so because the data are unreliable. Wide variations in survival figures in the medical literature are probably due to variations in staging conventions rather than different treatments. It is clear that cancer stages carry a more favourable prognosis, but it still cannot be proved that earlier diagnosis in a particular individual prolongs the life of that individual. This unproven hypothesis is the rationale for mammographic screening. Data on treatment in hospitals do not link diagnosis to operation, so that it is impossible to separate operations for benign breast disease from those for cancer. The OPCS classification of operations is complex with many open-ended choices. Doctors do not participate in the coding process and clerks cannot make up for this. Radiotherapy and chemotherapy data are not collected nationally and the four regional registries who do collect it also rely on their clerks' interpretation of medical notes. Data on the use of tamoxifen are consistent and of high quality.An extensive data gathering mechanism is in place for breast cancer. A huge body of information exists about the disease which should form a valuable database. The poor quality of this information reduces its usefulness. It is the responsibility of doctors to agree on a data set and to ensure its collection. They do it in Scandinavia. PMID- 1759767 TI - Sedation for day-case urology: an assessment of patient recovery profiles after midazolam and flumazenil. AB - The specific antagonist flumazenil has been shown to reverse the central actions of benzodiazepines. Its use, in day-case procedures performed under benzodiazepine sedation, offers the potential for enhanced patient recovery. However, concern has been expressed over the possibility of resedation given the short elimination half-life of flumazenil. A randomised, double-blind, placebo controlled trial was therefore designed to assess patient recovery profiles after flumazenil. A total of 44 adults were entered into the trial. Recovery was assessed by means of a battery of psychomotor tests performed pre- and postoperatively. Psychomotor function in patients receiving flumazenil returned to, or near to, baseline levels within 15 min of administration--an improvement maintained throughout the 6 h test period. Patients receiving placebo did not recover fully until the 2 h test point--significant differences between the two groups existing at 15 min and 1 h. In this study, flumazenil effectively reversed midazolam-induced sedation without evidence of resedation. The implications for day-case surgery are discussed. PMID- 1759768 TI - Branchial cysts: congenital or acquired? AB - Branchial cysts are one of the commonest causes of neck lumps in the young adult. Their aetiology is the subject of some controversy, although available evidence suggests that they are derived from lymphoid tissue. We present two cases of branchial cysts, and emphasise the importance of excluding more sinister causes of neck lumps before excision, even when the clinical features suggest benign pathology. PMID- 1759769 TI - Postoperative collection and reinfusion of autologous blood in total knee arthroplasty. AB - A series of 40 patients undergoing primary unilateral total knee arthroplasty were entered into a randomised controlled trial to assess the safety and efficacy of postoperative autologous blood salvage and reinfusion. The mean volume of autologous blood reinfused was 520 ml per patient (51% of the mean total drainage). Homologous blood transfusion was required in only 35% of patients in the study group compared with 95% of patients in the control group (P less than 0.001). The mean volume of homologous blood transfused was 0.9 units per patient in the study group compared with 2.5 units in the control group (P less than 0.001), a saving of 64%. PMID- 1759770 TI - Proposed definitions for the audit of postoperative infection: a discussion paper. Surgical Infection Study Group. AB - Infection is an important arbiter of success or failure of surgical practice and the incidence of infection is incorporated into all surgical audit systems. If audit is to be of value the outcome end points of clinical practice must be defined. We have attempted to derive clinical definitions suitable for bedside diagnosis of infection and believe that these should bs supported by, but not be dependent upon, the results of laboratory or imaging techniques. The proposed definitions are intended to form the basis for clinical audit and to allow meaningful comparisons to be made on clear clinical criteria. PMID- 1759771 TI - Use of operating theatres: the effects of case-mix and training in general surgery. AB - Details of theatre occupancy times for a surgical unit in a district general hospital and associated cottage hospital were recorded over a 4-month period. The average time of the procedures individually and reclassified within the BUPA schedule showed that both the severity of the procedure and the grade of surgeon influenced future theatre needs. For almost every type of procedure, as expected, consultants were quicker than registrars, who in turn were faster than SHOs. The hidden cost of training surgeons in general surgical operative procedures can be estimated as a result. It is concluded that current measures of resource use which rely only on the bed use and ignore operating theatre needs and training requirements for non-consultant grades will be misleading, particularly in relation to the large element of minor or intermediate surgery which constitutes the bulk of most district health authorities' workload. PMID- 1759772 TI - Surgical options for left-sided large bowel emergencies. AB - Current choices of operation for left-sided large bowel emergencies have been established by a questionnaire sent to 218 consultant surgeons asking which operation they would perform under varying circumstances for obstructing sigmoid carcinoma and diverticular disease. A 92% response rate was obtained. Hartmann's procedure (with or without a mucus fistula) is the most popular operation for all conditions. Sigmoid colectomy with primary anastomosis is performed by 40% of surgeons for obstructing carcinomas, but less commonly in other situations. On table lavage is rarely used, and the majority of anastomoses are not protected by a proximal stoma. Subtotal colectomy is very seldom employed, except when caecal perforation results from an obstructing carcinoma. Some surgeons perform a defunctioning colostomy alone even in the presence of a perforation. PMID- 1759773 TI - Outpatient carpal tunnel decompression without tourniquet: a simple local anaesthetic technique. PMID- 1759774 TI - Early endoscopic sphincterotomy for retained bile duct stones after gallbladder surgery. PMID- 1759775 TI - A comparative study between Michel and Proximate clips for closure of neck incisions. PMID- 1759776 TI - The incidence and value of rectal examination in children with suspected appendicitis. PMID- 1759777 TI - The management of popliteal aneurysm: the importance of early surgical repair. PMID- 1759778 TI - Two kinds of diverticular disease. PMID- 1759779 TI - Beds or day case unit: your choice? AB - The aim of this study was to assess the amount of day case surgery and potential day case surgery being performed in the main theatre block of a District General Hospital, which had a thriving Day Case Unit. Our results revealed that as well as large numbers of potential day cases being performed as inpatients, many patients (both potential day cases and long-stay elective surgery patients) are spending a day(s) in hospital prior to the day of surgery. We believe that by performing all day case surgery in our Day Case Unit and by using the Day Case Unit to perform pre-admission screening on all surgical patients, a large number of bed days will become available. These beds may be used for elective or emergency admissions. Alternatively, cutting surgical beds will free monies which can be spent on the Day Case Unit. PMID- 1759780 TI - Comparative audit: a new method of delivering audit. AB - A new method of audit delivery is described, based on the first large scale comparative audit meeting held at The Royal College of Surgeons of England. The concept of comparative audit is introduced and the methods of undertaking such an exercise are described. This comparative audit processed the clinical activity of 45 general surgeons during 1989 amounting to 49,005 patient admissions. As an illustration of this technique the comparative analysis of 3,710 inguinal hernia procedures accounting for 12,600 total stay days is used in order to illustrate data manipulation, ranking and presentation in chart form. Conclusions are drawn and suggestions as to the future role of the technique are outlined. PMID- 1759781 TI - An audit of hospital mortality: general compared with vascular surgery. AB - We have prospectively analysed hospital mortality for general and vascular surgical patients on a single surgical unit. During 1990, 1277 patients were admitted (836 general, 368 vascular, 73 varicose veins). The mortality for the general surgical patients was 1.3 per cent, vascular 6.2 per cent and no varicose vein patients died. All of the general surgical deaths and 70 per cent of the vascular deaths were in-patients admitted as an emergency. The major causes of death in general surgical patients were peritonitis and gastrointestinal bleeding, whilst those of the vascular patients were ruptured abdominal aortic aneurysms and acutely ischaemic legs. The implications of these findings are discussed. PMID- 1759782 TI - [Should digitalis preparations be prescribed for patients with cardiac sinus rhythm insufficiency?]. PMID- 1759783 TI - [Comparative study of 4 ultrasonic methods for evaluating the severity of mitral valve narrowing. Apropos of 36 cases]. AB - Four ultrasound methods of estimating the severity of mitral narrowing (MN) were investigated in a prospective manner in 36 patients who underwent ultrasound Doppler and catheterization (KT) within a space of 24 hours. The correlation of the mean Doppler and KT gradients was poor: r = 0.56 (n = 36, p less than 0.001). The mitral surface areas (MA), calculated from Gorlin's equation (mean A = 0.98 +/- 0.26 cm2) were successively compared with those obtained using the Hatle equation (A = 220/PHT) and by a planimetric determination. The coefficients of correlation were as follows: r = 0.80 (n = 36) and r = 0.70 (n = 32) (p less than 0.001). There was good correlation between the Hatle equation and the planimetric determination: r = 0.80 (n = 32, p less than 0.001). The continuity equation was carried out 15 times; the second measurement site was aortic in 8 cases and pulmonary in 7 cases. Correlations with the Gorlin equation were scored 0.70 and 0.80 respectively (p less than 0.05). The MA was best estimated by the Hatle equation, which was always technically feasible and not influenced by the presence of atrial fibrillation, mitral valve incompetence of previous commissurotomy. Planimetric determination, which is hampered in the presence of considerable calcification, remains valid after commissurotomy. The ultrasound estimation of the MA was very reliable when the planimetric and Hatle estimations concurred. The results obtained from the continuity equation were reliable; however, this method is slow, unreliable in a context of atrial fibrillation and inapplicable in a context of mitral valve incompetence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759784 TI - [Left bifascicular block and percutaneous mitral valvuloplasty]. AB - In some patients, the inflation of balloons through the mitral orifice during percutaneous mitral valvuloplasties may impair intraventricular conduction. In some cases, this appears to correspond to a block of the anterior and middle network within the left branch of the bundle of His. This left "biblock" is characterized by extreme left axial deviation of AQRS, of about -60 to -70 degrees, with a QS aspect on D2 and D3, RS on V1 and R on V6 with no major prolongation of ventricular activation time. If this hypothesis is correct, it would support the "trifascicular" concept of the left branch of the bundle of His. PMID- 1759785 TI - [A consultation service for the correction of risk factors of atherosclerosis in hospitals]. AB - Although the main risk factors for atherosclerosis have been clearly identified and their correction has demonstrated its efficacy, many subjects do not receive the corrective measures appropriate for their case. The authors describe a hospital service for the prevention of atherosclerosis, which is intended for both primary and secondary prevention as well as for epidemiological monitoring and above all the evaluation of the preventive strategies employed. The results after the service has been running for one year are reported. They appear to confirm the initial options. Cooperation with other people involved in prevention both inside and outside the hospital, is also a fundamental aspect of this task. PMID- 1759786 TI - [Sudden syncope and myocardial ischemia. Apropos of a case]. AB - It is unusual to carry out a systematic search for myocardial ischemia in patients who have suffered a sudden syncopy with no known history of angina. We report a case involving loss of consciousness (LC) in the context of sub-hissian atrioventricular block (AVB) which required the installation of a pacemaker, with the detection of angina pectoris immediately after its installation. Coronary artery angiography confirmed a diagnosis of severe, multitrunk coronary disease characterized by a tight stenosis of the common trunk. If consciousness is lost by a patient suffering from baseline conduction impairment with no chest pain, the first thought is 3rd degree degenerative paroxysmal AVB but the possibility of an ischemic origin of this AVB should not be overlooked. PMID- 1759787 TI - [Right arrhythmogenic ventricular dysplasia. A propos of 2 cases]. AB - The authors report two new case histories of arrhythmogenic ventricular dysplasia. The disease was manifest as usual by recurrent ventricular tachycardia with apparent left lagging. Follow-up was 10 and 2 years. A review of the diagnostic and therapeutic approaches is provided based on this short personal series and on data from the literature. PMID- 1759788 TI - [Determination of cardiac output by Doppler ultrasonics. Principle, techniques and limitations]. AB - The development of quantitative applications of Doppler ultrasound for the measurement of cardiac output was a lengthy and difficult process. These applications call for rigor of the part of the ultrasound cardiographer and a sufficiently echoic patient. Numerous studies have demonstrated the reliability of Doppler ultrasound in determining aortic flow. A high degree of consensus has emerged for measuring aortic areas and velocities at the ring. Doppler ultrasound quantification of the pulmonary flow has been validated in children. In adults, measurement of the pulmonary ring is often difficult and may lead to major errors in the estimation of the flow rates. The determination of mitral flow is also possible, either at the ring or at the tip of the mitral funnel. A few publications highlight the value of Doppler ultrasound in evaluation of tricuspid flow, however, these results require confirmation. PMID- 1759789 TI - [Comparison of the efficacy and tolerability of sustained-release verapamil and captopril in mild to moderate essential arterial hypertension]. AB - A randomised, double-blind, double-placebo trial compared the efficacy and safety/acceptability of sustained release verapamil and of captopril in two parallel groups of patients with mild to moderate hypertension. After a 2 week placebo period, 45 patients were randomised into 2 groups, the 1st group (n = 22) given sustained release verapamil (240 mg/24 h) as a single morning dose and the second (n = 23) captopril 25 (50 mg/24 h) as two daily divided doses. Treatment was given for 75 days, with the possibility of a combination of sustained release verapamil + captopril from day 45 onwards if diastolic blood pressure remained at 95 mmHg or more. After 45 days of treatment, the reduction in supine diastolic blood pressure did not differ significantly in the 2 groups (-10.4 mmHg in the sustained release verapamil group and -9.7 mmHg in the captopril), with 68.2 per cent responders to sustained release verapamil and 52.2 per cent in the captopril group. After 75 days of treatment, once again there was no significant difference in efficacy between the two groups: -14 mmHg for diastolic pressure and 80 per cent responders in patients treated with sustained release verapamil, -11.3 mmHg and 62.5 per cent responders in the captopril group. The percentage of responders was 58.3 per cent in the group treated with the combination of sustained release verapamil + captopril from day 45 onwards. The number of patients showing evidence of clinical or electrocardiographic adverse reactions was not significantly different: 20.7 per cent in the sustained release verapamil group and 34.8 per cent in the captopril group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759790 TI - Current clinical use of absorbable fracture fixation devices. PMID- 1759791 TI - Ischaemic colitis--a clinical study of seven patients with special emphasis on diagnostic problems. AB - Ischaemic colitis is a relatively rare but well-defined disease entity. It is associated with high mortality rate if early diagnosis and adequate surgical treatment is not accomplished. The aim of the present study was a clinical analysis of 7 patients with the verified ischaemic colitis. The delay from admission to the correct diagnosis was 8 days on the average (range 2-15 days). The reasons for delayed diagnosis included suspicion of diverticulitis, Crohn's disease and bowel obstruction as well as poor general condition in one case because of which early colonoscopy was not done. It is concluded that in patients with abdominal pain, rectal bleeding and diarrhoea associated with typical clinical findings, ischaemic colitis should be suspected. This suspicion should be followed by early colonoscopy to detect the gangrenous form of the disease as early as possible. Instant laparotomy and excision of the affected bowel is necessary for cure in these patients. PMID- 1759792 TI - Primary small intestinal non-Hodgkin's lymphoma in Finland 1972-1977. Clinical presentation and results of treatment. AB - During the period of 1972-1977, 29 patients were treated for primary non Hodgkin's small intestinal lymphoma (PSIL) in different hospitals in Finland. Most frequently the disease occurred in patients in middle age and there was a male predominance. Clinical symptoms were non-specific. An abdominal mass was felt in 31% of the patients. Radiological findings were mostly non-specific, and often a stricture was revealed. All patients underwent surgery, ten patients curative resection, 15 patients palliative resection and 4 patients exploration and biopsy only. Sixty per cent of the patients who underwent curative resection survived five years compared with ten per cent who underwent palliative resection. The stage of the disease was an important prognostic factor. The five year survival was 60% for patients with stage I disease, while all the patients with stage IV disease died during the first two years. PMID- 1759793 TI - Computed tomography is important in assessing resectability of pancreatic carcinoma, even after ultrasonographic demonstration of the tumour. AB - In Finland pancreatic tumour is often detected initially on ultrasonography (US), which is widely used as a primary examination in patients who have epigastric pain or are jaundiced. This retrospective study was performed to investigate whether computed tomography (CT) provided any essential substantial staging information to US in patients, whose primary tumour was detected in US. Both US and CT had been performed in 102 pancreatic carcinoma patients. US, being performed always prior to CT, detected the pancreatic tumour in 73 patients (sensitivity 72%). CT detected pancreatic tumour in 65 of these 73 patients (89%). US demonstrated the tumour to be unresectable in 22 patients (30%). CT demonstrated the tumour as unresectable in the same 22 patients, but also in additional 20 patients (overall 42 patients = 58%, P less than 0.001 as compared to US). Three of these 20 patients underwent biliary bypass, but in 17 patients laparotomy was considered unnecessary (including the six patients who underwent merely exploratory laparotomy). It was estimated, that the 51 CT examinations, performed in patients in whom the pancreatic tumour was detected resectable on US, with overall costs of about FIM 137,700, might obviate laparotomy in 17 patients, with operative costs of about FIM 255,000. Thus, CT appears to provide essential substantial information to US about the resectability of pancreatic carcinoma, and CT can be considered a very important preoperative examination from both medical and economical point of view in the patients whose pancreatic tumour has been demonstrated by US. PMID- 1759794 TI - Clinical results of abdominal rectopexy for rectal prolapse. AB - Abdominal Marlex-mesh rectopexy was used for surgical treatment of rectal prolapse in 54 consecutive patients. Anal incontinence was observed in 43 patients (80%) before surgical treatment. The degree of anal incontinence was more severe in women as compared with men. Operative treatment corrected the pathologic anatomy effectively as only one recurrent prolapse developed. At the follow-up examination three patients had symptomless anal mucosal prolapse during maximal straining. 75% of the incontinent patients regained continence for faeces and the rest had some improvement in continence. Seventeen patients (31%) had postoperative constipation, that required lactulose treatment. In conclusion, abdominal Marlex-mesh rectopexy can be recommended as safe and effective treatment for rectal prolapse, despite some patients developing constipation and some remaining incontinent. PMID- 1759795 TI - Pneumatic dilatation in oesophageal achalasia. Factors influencing results. AB - Pneumatic dilatation was performed for oesophageal achalasia in 19 consecutive patients without previous endoscopic or surgical treatment. There were no complications. Relief of symptoms was excellent or good in 11 cases during follow up averaging 43 months. The outcome was better in patients older than 45 years than in younger patients. More than two repetitions of dilatation did not improve the results. Modified Heller's cardiomyotomy was performed on five patients with poor result after two to six dilatations. Pneumatic dilatation is safe and effective as initial treatment of oesophageal achalasia particularly in older patients, with cardiomyotomy reserved for those who do not respond to two dilatations. PMID- 1759796 TI - The results of completion angiography after acute lower limb thromboembolectomy. AB - The results of completion angiography after acute thromboembolectomy with a Fogarty balloon catheter were evaluated. There were 62 patients (median age 72 years, range 44-92 years) and completion angiograms were made in 44 of them (71%). Incomplete runoff was demonstrated in 26 patients (59%) and rethromboembolectomy or vascular reconstruction was made in 18 cases (41%) under the same anaesthesia, while additional vascular surgery was technically impossible in 8 patients (18%). Supplementary surgery resulted in radiological improvement in 56% of operated cases. Reocclusion rate after 6 months was 50% in patients without patent tibials compared to 15% in patients with two or three patent tibial arteries (P less than 0.05). Eighteen patients had no completion angiograms after thromboembolectomy and 5 (28%) required early reoperation due to ischaemia. Completion angiograms are advocated in all cases of acute thromboembolectomy before the patient leaves the operating table. PMID- 1759797 TI - Fixation of experimental osteotomies with absorbable polylactic acid screws. AB - Absorbable screws made of self-reinforced poly-L-lactic acid (SR-PLLA) and poly DL/L-lactic acid (SR-PDLLA/PLLA) were used for fixation of cancellous bone osteotomies of the distal femur in rabbits. The initial molecular weight of PLLA was 260.000 and that of PDLLA 100.000. The follow-up times were from one week to 96 weeks. Seventy-two rabbits were operated on, 36 in the PLLA group and 36 in the PDLLA/PLLA group. After sacrifice, radiographic, micro-radiographic, histologic, histo-morphometric, and oxytetracycline-labelling studies were performed. In the PLLA group 34/36 (94%) osteotomies and in the PDLLA/PLLA group 31/36 (86%) osteotomies healed without delay or angular deformity. The present investigation shows that absorbable SR-polylactic acid screws are suitable for fixation of weight loading cancellous bone osteotomies in rabbits. Based on these promising results, a clinical study where cancellous bone fractures are fixed with SR-PLLA screws has been started. PMID- 1759798 TI - Bone malalignment in acute injuries of the wrist. AB - The purpose of this study was to analyze radiographic signs of carpal bone instability in patients with an acutely injured wrist. There were 80 patients (52 women and 28 men) with a fall on the outstretched hand. Fifty patients had a fracture of the distal radius, and eight had a scaphoid fracture. The patients with a bone fracture showed a larger scapholunate angle than those without a fracture (P less than 0.001, t-test). However, only four of them showed true carpal bone instability: two patients with a scaphoid fracture and one with a radius fracture had dorsiflexion instability of the wrist and one patient with a radius fracture had dorsal subluxation of the wrist. In addition, one patient without any bone fracture had scapholunate dissociation, one form of carpal bone instability. Although carpal bone instability is not frequent in an acutely injured wrist, its signs should be remembered in the radiographic analysis of the traumatic wrist to prevent subsequent articular disorders. PMID- 1759799 TI - Clinical evaluation of fracture healing by serum osteocalcin and alkaline phosphatase. AB - The serum osteocalcin (BGP) concentration and alkaline phosphatase (AP) activity were measured prospectively during the healing phases of crural fractures in 15 patients. They were divided into two groups, the time of union of the fracture being under (group 1) or over 16 weeks (group 2). The mean values of BGP and AP were somewhat higher from the outset in the group 1 than in the group 2, but the difference was not significant. A significant increase in BGP and AP (P less than 0.05) was evident in both groups at 6 weeks. In cases with undisturbed healing of fractures (group 1) the values of serum BGP and AP then declined towards the values at the time of accident. Contrary to this, in group 2 both the values of the serum BGP and AP were still at a significantly higher level than those at the day of the fracture. However, no significant difference in the serum BGP or AP was seen between the two groups at 6 or 12 weeks. The results support some earlier ones: the changes in serum BGP and AP may provide a prognostic indicator for consolidation of a fracture. PMID- 1759800 TI - Conservative treatment of tibial fractures. Results in a series of 163 patients. AB - The purpose of this study was to assess the results of conservative treatment of tibial fractures. The series consisted of 165 tibial fractures in 163 consecutive patients. Over one-fifth (35) were open fractures. The treatment was in the main conservative, the primary treatment of only three fractures was operative. Full weight-bearing was started after 124 days on average. The average duration of primary treatment by plaster immobilization was 99 days. A questionnaire was completed and returned by 84% of the patients. Symptomatic, clinically and radiologically evident deep venous thrombosis was observed in 0.6%, pulmonary embolism in 1.9%, signs of fat embolism in 1.9%, superficial infection in 3.1%, osteitis in 0.6% and refracture in 2.5% of fractures. The average time to union was about 14 weeks. The incidence of radiological malpositions developing during the time of treatment was high. The risk of shortening was associated with oblique and severely comminuted fractures and possibly also with severely displaced fractures. Subjective sequelae were reported by a large number of patients. An optimal result is not guaranteed in all tibial fractures by conservative treatment. PMID- 1759801 TI - Effect of prolonged experimental distension on the function and ultrastructure of the canine urinary bladder. AB - Urinary bladder distension was induced for 10 hours in dogs and micturition tests were made before over-stretching, immediately afterwards and 5 days later. Compliance and residual urine had increased and maximum pressure during voiding had decreased immediately after retention, but returned to normal after 5 days. Biopses for light microscopic and electronmicroscopic investigation taken from the anterior wall of the bladder on the fifth day showed submucosal haemorrhages and some necrosis. The consistent finding on electron microscopy was Schwann cell oedema, which was seen within the cytoplasm and between the cytoplasmic processes of the Schwann cells. Axonal degeneration was also a common finding. These anatomical changes, although found at the moment of functional recovery, may be linked to impaired conductivity of the nerves in the bladder wall, at least partly, causing its impaired function. Recovery of function occurs quite rapidly in healthy bladders. PMID- 1759802 TI - Fibroepithelial polyps of the ureter. AB - Two cases of ureteric fibroepithelial polyps are presented. Macroscopic haematuria and flank pain were seen as symptoms in both cases. Intravenous urography, retrograde ureteropyelography, computed tomography, and ureterorenoscopy with visual biopsies were used as diagnostic methods. As a result of the preoperative diagnostics, saving surgical procedures (local excision and coagulation of the base of the tumour) were used with good results. The therapy of ureteric tumours should always be founded on the preoperative histological diagnosis and should be conservative transureteric or open surgical. PMID- 1759803 TI - Primary arterioenteric fistula between common iliac artery and ileum with massive bleeding. AB - Primary iliac artery aneurysms are rare, and a fistula to the terminal ileum with bleeding is very uncommon. A case with a primary massively bleeding iliaco-ileal fistula is described. In an emergency operation the common iliac artery was ligated and the fistula to the small bowel was resected. Arterial reconstruction was done by extra-anatomical femoro-femoral suprapubic prosthesis. The immediate outcome of the operation was excellent, but the patient died four days later because of acute myocardial infarction. PMID- 1759804 TI - Traumatic luxation of the heart. AB - A case of luxation of the heart resulting from blunt thoracic trauma is presented. Pericardial defect with herniation of the heart was discovered preoperatively and successfully repaired with a pleural patch. Special attention is drawn in the report to the preoperative diagnosis of this life-threatening condition. PMID- 1759805 TI - Recurrent strangulated obturator hernia. AB - A case of recurrent strangulated obturator hernia is presented. The difficulty in diagnosing obturator hernia and the high mortality associated with strangulation are highlighted from a literature review. A high index of suspicion in older patients presenting with intestinal obstruction without an obvious cause, possibly combined with CT scanning of the pelvic region, may lead to earlier diagnosis and operation and a more favourable outcome in such cases. PMID- 1759806 TI - The role of experience, narrative, and community in skilled ethical comportment. AB - Two major types of narrative--constitutive or sustaining narratives and narratives of learning--are presented to illustrate the functions of narrative in everyday ethical expertise and socially embedded caring practices. Four narrative themes illustrate constitutive and sustaining narratives: healing and transcendence, the heroic saving of a life, fostering care and correction, and stories of being present. Five themes illustrate narratives of learning: the skill of involvement, being open to experience, disillusionment, facing death and suffering, and liberation. Quandary- and rights-based procedural ethics address ethical problems and breakdown and overlook everyday ethical comportment. Public storytelling is recommended as a way to explore notions of the good and ethical concerns. PMID- 1759807 TI - Principle-oriented ethics and the ethic of care: a creative tension. AB - Research to date in the field of nursing ethics has overlooked the nature of the guiding moral framework in nursing practice, while focusing primarily on the moral reasoning and moral behaviors among nurses. This research depicts two moral frameworks--a principle-oriented ethic and the ethic of care--as they are experienced by practicing critical care nurses. The interdependence of these two frameworks as they inform the moral experience of the nurse is demonstrated in the analysis of a complex nurse narrative that depicts the nurse's moral struggle. PMID- 1759808 TI - Pain assessment in children: theoretical and empirical validity. AB - Valid assessment of pain in children is foundational for both the nursing practice and research domains, yet few validated methods of pain measurement are currently available for young children. This article describes an innovative research approach used in the development of photographic instruments to measure pain intensity in young African-American and Hispanic children. The instruments were designed to enable children to participate actively in their own care and to do so in ways that are congruent with their developmental and cultural heritage. Conceptualization of the instruments, methodological development, and validation processes grounded in Orem's Self-Care Deficit Theory of Nursing are described. The authors discuss the ways in which the gaps between nursing theory, research, and practice are narrowed when development of instruments to measure clinical nursing phenomena are grounded in nursing theory, validated through research and utilized in practice settings. PMID- 1759809 TI - The meaning of nursing home friendships. AB - This research report on the social networks of institutionalized elderly people describes four types of networks and focuses on resident-resident interaction. Friendship themes of intimacy, social support, reciprocity, and companionship provide a basis for examining similarities in and differences between the network types. Discussion draws on the study results through examination of the meaning of friendship and interpretation of life-span themes. PMID- 1759810 TI - Patient outcomes research: seizing the opportunity. AB - Nurses must take a proactive role in patient outcomes research. Because the patient, not disease, has always been the focus of nursing, nurses are sensitized to the rich but complicated context in which patient outcomes research will be conducted. Nurse researchers are experienced in using complex research models, dealing with ambiguous concepts, grappling with difficult measurement issues, and subscribing to methodological pluralism. These skills are important to success with patient outcomes research. In this article, the opportunities and challenges posed to nurses by patient outcomes research will be addressed. One of the benefits will be a stronger knowledge base for clinical practice and hence patient care. PMID- 1759811 TI - Studying the human-environment phenomenon using the science of complexity. AB - The principal argument of the present article is that a new theoretical paradigm capable of facilitating the understanding of complex phenomena is necessary to study nursing's claim to its science as the science of unitary human beings, or the integrality between humans and the environment. A research study of the complex human-environment phenomenon illuminating a four-phase methodology is presented. It is argued that much can be learned by the use of the science of complexity to integrate data gleaned from different approaches to knowledge generation into a comprehensive understanding of the human being in the environment as a unified whole. PMID- 1759812 TI - Antibiotic tissue penetration and its relevance: models of tissue penetration and their meaning. PMID- 1759813 TI - Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response. PMID- 1759814 TI - In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center. AB - To determine whether the prevalence of resistance to commonly used oral antimicrobial agents varied over time, we compared the in vitro susceptibilities of 217 strains of Haemophilus influenzae recovered from nasopharyngeal secretions of children in a day-care center studied longitudinally between 1979 and 1987. The overall rate of beta-lactamase production in these strains was 18%, with rates of 57% in type b isolates (n = 21) and 14% in non-type b isolates (n = 196). The percentages of isolates for which MICs were less than or equal to 1.0 micrograms/ml for amoxicillin alone, amoxicillin in combination with clavulanic acid, and cefuroxime alone were 82, 92, and 93%, respectively. The percentage of strains for which cefaclor MICs were less than or equal to 1.0 micrograms/ml was only 0.5%. Isolates for which chloramphenicol MICs were greater than 2.0 micrograms/ml or for which trimethoprim-sulfamethoxazole MICs were greater than 0.5/9.5 micrograms/ml were uncommon: 1 and less than 1%, respectively. High concentrations of erythromycin alone and in combination with sulfisoxazole were required to inhibit the majority of test strains; there was no evidence of erythromycin-sulfisoxazole synergy. In vitro susceptibility to commonly used oral antimicrobial agents remained at a constant level when H. influenzae isolates collected from children in a day-care center during 1979 through 1983 were compared with strains collected during 1984 through 1987. PMID- 1759815 TI - Microculture screening assay for primary in vitro evaluation of drugs against Pneumocystis carinii. AB - Pneumocystis carinii inoculated into 96-well filtration plate assemblies was shown to synthesize radiolabeled folates de novo from [para-3H]aminobenzoic acid ([3H]pABA). At the end of each incubation with [3H]pABA, a vacuum manifold was used to remove the medium and wash P. carinii. The membrane at the base of each well was dried and punched out, and the level of 3H retained was determined by direct scintillation counting. High-pressure liquid chromatography analysis of duplicate filters confirmed that direct counting of 3H retained on membranes (after correction for unmetabolized [3H]pABA) was an accurate reflection of total [3H]pABA incorporation by P. carinii. Greater than 95% of the 3H recovered was shown to be present as polyglutamated species. After digestion with rat plasma folic acid gamma-glutamyl hydrolase, para-aminobenzoylglutamate, N10 formyltetrahydrofolate, and tetrahydrofolate were identified as the major 3H labeled components. para-Aminobenzoylglutamate was presumed to have arisen from folylpolyglutamates synthesized by P. carinii and was therefore included in the calculation of total [3H]pABA incorporation. P. carinii incorporation of [3H]pABA under optimal conditions was used as a selective measure of in vitro viability against which the inhibitory effects of some antipneumocystis agents (pentamidine, sulfamethoxazole, 566C80, and piritrexim) were quantitated. The concentrations of pentamidine, sulfamethoxazole, 566C80, and piritrexim required for 50% inhibition in this assay were 7.3, 0.1, 1.4, and approximately 100 microM, respectively. The results suggest that this 96-well [3H]pABA incorporation assay has considerable potential for objective in vitro drug screening against P. carinii. PMID- 1759816 TI - Borderline susceptibility to antistaphylococcal penicillins is not conferred exclusively by the hyperproduction of beta-lactamase. AB - Staphylococcus aureus strains bearing the 17.2-kb beta-lactamase plasmid pBW15 and belonging to phage group 94/96 exhibit borderline susceptibility to the antistaphylococcal penicillins. Borderline susceptibility within phage group 94/96 is thought to be mediated by the hyperproduction of type A staphylococcal beta-lactamase. Evaluation of 84 non-94/96 phage type S. aureus strains that also produced the type A enzyme identified 7 additional hyperproducing strains. However, none of these isolates contained pBW15, and only one met the criteria for borderline susceptibility. To determine the role of pBW15 and the 94/96 phage type in the expression of borderline susceptibility, pBW15 was transformed in two plasmid-free, penicillin-susceptible strains, one of which belonged to phage group 94/96. Penicillin MICs for both transformants and quantitative beta lactamase activity were comparable to those for the parent pBW15-containing strain. A fourfold difference in the oxacillin MICs for the 94/96 and non-94/96 phage type transformants (1.0 and 0.25 microgram/ml, respectively) was identified, and only the 94/96 phage type transformant met the criteria for borderline susceptibility. Chromosomal DNA from borderline-susceptible phage group 94/96 strains did not hybridize with a probe for mecA, and the beta-lactam binding affinity of PBPs 1, 2, 3, and 4 from a penicillin-susceptible 94/96 phage type strain and a non-94/96 phage type strain were comparable. Although hyperproduction of the type A beta-lactamase appears to be necessary for the expression of borderline susceptibility within certain phage group 94/96 strains, beta-lactamase production of a comparable magnitude by a group of S. aureus strains belonging to other phage types does not confer borderline susceptibility. These data suggest that borderline susceptibility is not solely due to the hyperproduction of beta-lactamase. PMID- 1759817 TI - Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection. AB - Modulation of the host's inflammatory response in bacterial meningitis may be beneficial. In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied. Five-day-old infant rats were inoculated once intraperitoneally with 1 x 10(4) to 10 x 10(4) CFU of H. influenzae type b (strain 1406). Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g). Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P less than or equal to 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups. Overall, dexamethasone was associated with less inflammation (P less than 0.04) of the cochlear nerve compared with that from antibiotic treatment alone. In this model, when suboptimal antimicrobial therapy is administered, anti inflammatory agents may be beneficial with respect to reducing cochlear inflammation. However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone. PMID- 1759818 TI - Efficacy of SCH 39304 in treatment of experimental invasive aspergillosis. AB - The efficacy of SCH 39304 (SCH) against Aspergillus fumigatus was assessed with an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with SCH at 10 or 15 mg/kg of body weight per day was begun 24 h after lethal challenge and compared with therapy with amphotericin B at 1.5 mg/kg/day. Compared with untreated controls, SCH reduced mortality and also reduced the tissue burden of A. fumigatus 100- to 1,000-fold in liver, kidney, and lung tissues. SCH at 15 mg/kg/day and amphotericin B eliminated A. fumigatus in liver, kidney, and lung tissues. In addition, both dosages of SCH significantly eliminated the organism from brain tissues, compared with controls. Both SCH and amphotericin B decreased or eliminated circulating aspergillus antigen. These results show that new azoles can be as effective as amphotericin B in eradicating the organism from tissues and offer promise in improving the treatment of invasive aspergillosis. PMID- 1759819 TI - Characterization of erythromycin resistance in Campylobacter jejuni and Campylobacter coli. AB - The mechanism of resistance to erythromycin, the drug of choice in the treatment of campylobacter gastroenteritis, was investigated. Erythromycin resistance (MICs, greater than 1,024 micrograms/ml) in three clinical isolates of Campylobacter jejuni and one C. coli isolate was determined to be constitutive and chromosomally mediated. In vivo protein synthesis in erythromycin-susceptible C. jejuni and C. coli strains was completely inhibited by low levels of erythromycin (5 micrograms/ml), whereas a high concentration of the antibiotic (100 micrograms/ml) had no effect on protein synthesis in erythromycin-resistant strains. Biological assays showed that extracellular degradation of erythromycin was not responsible for erythromycin resistance in strains of Campylobacter species. The rates and amounts of uptake of [14C]erythromycin by resistant and susceptible campylobacter cells were determined to be similar. Binding assays with purified campylobacter 70S ribosomes as well as 50S ribosomal subunits showed that those from erythromycin-resistant strans bound much less [14C]erythromycin than did those from susceptible strains. Genomic DNA from C. coli UA585 was used to transform erythromycin resistance to C. coli UA417. The erythromycin resistance marker was associated with a 240-kb SmaI fragment of the C. coli UA585 genome. Our results rule out erythromycin inactivation or efflux and are not consistent with the production of an RNA methylase, although they are consistent with a mutational mechanism of resistance due to a change in a ribosomal protein gene. This study constitutes a detailed biochemical and genetic characterization of erythromycin resistance in Campylobacter species. PMID- 1759820 TI - Chlorhexidine resistance in methicillin-resistant Staphylococcus aureus or just an elevated MIC? An in vitro and in vivo assessment. AB - Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether the chlorhexidine MIC for methicillin-resistant S. aureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is relevant. In addition, the link between resistance to chlorhexidine, gentamicin, and "nucleic acid-binding" compounds (NAB; which code, in particular, for propamidine isethionate and ethidium bromide) requires clarification. We performed chlorhexidine MIC and rate of kill tests on a number of MSSA and MRSA isolates. Two gentamicin-resistant MRSA isolates without NAB plasmids were more susceptible (0.25 and 0.5 microgram/ml) than four of eight MSSA that we tested (range, 0.25 to 2 microgram/ml). Chlorhexidine MICs were higher (4 to 8 micrograms/ml) for seven distinct MRSA isolates with plasmids conveying resistance to gentamicin and NAB (GNAB). Curing of the GNAB plasmid from MRSA strains resulted in a fall in the MIC (1 to 3.3 micrograms/ml), but no consistent fall in killing by chlorhexidine was observed. No effect on the chlorhexidine MIC or killing was observed when we cured strains of methicillin resistance. GNAB plasmid transfer resulted in a rise in the chlorhexidine MIC for the strains but not consistent fall in killing by chlorhexidine. Ethical approval was granted for 10 volunteers to each have a methicillin-susceptible, GNAB-resistant, derived transcipient and its GNAB-susceptible isogenic parent applied to separate sites in an in vivo skin test; no significant difference was seen in survival rates after the application of chlorhexidine. These results suggest that chlorhexidine appears to be as effective as a hand-washing agent for MRSA isolates with or with out NAB plasmids as it is for MSSA isolates. PMID- 1759821 TI - Novel method for measuring growth of Treponema hyodysenteriae and its application for monitoring susceptibility of clinical isolates to antimicrobial agents. AB - A microdilution assay method was developed to determine MICs of antibiotics for Treponema hyodysenteriae and to estimate the bacterial burden of mice colonized by this swine pathogen. Hemolysis of bovine erythrocytes in broth was correlated with growth of the spirochete, and growth inhibition by drugs could be determined by measuring hemolysis. MICs of 10 antibiotics for eight clinical isolates of T. hyodysenteriae measured by this method were similar to values obtained by an agar dilution method and to values reported in the literature. This method was also used to demonstrate the elimination of T. hyodysenteriae from the ceca of infected mice following oral treatment with carbadox. The procedure described in this paper provides a rapid and simple method for determining MICs of antibiotics for T. hyodysenteriae and may be adapted for the purpose of determining the presence of this veterinary pathogen in cecal contents of experimentally infected mice. PMID- 1759822 TI - Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin. AB - Antibiotics do not act alone but act in conjunction with the host defense system. In particular, it has been shown that some antibiotics can modify cytokine production. We compared the in vitro effects of three macrolides (roxithromycin, spiramycin, and erythromycin) actively concentrated by leukocytes on interleukin 1 alpha, (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha production by human monocytes stimulated with lipopolysaccharide. Our results show that the three macrolides tested have different effects on production of these cytokines. Spiramycin and, to a lesser extent, erythromycin increased total IL-6 production without affecting IL-1 alpha, IL-1 beta, or tumor necrosis factor alpha production, whereas roxithromycin had no effect. To our knowledge, this is the first time that an antibiotic has been shown to increase IL-6 production. PMID- 1759823 TI - Use of a broad-host-range gyrA plasmid for genetic characterization of fluoroquinolone-resistant gram-negative bacteria. AB - The gyrA genotypes of ciprofloxacin-resistant clinical isolates of Escherichia coli (n = 3), Klebsiella pneumoniae (n = 4), Providencia stuartii (n = 2), Pseudomonas aeruginosa (n = 1), and Acinetobacter calcoaceticus (n = 1) were analyzed in a dominance test. This test is based on the dominance of a wild-type gyrA gene (gyrA+) over the quinolone resistance allele (gyrA) in a heterodiploid strain. Plasmid pBP515, developed to carry the gyrA+ gene of E. coli K-12 on a broad-host-range vector derived from pRSF1010, was used to obtain heterodiploid strains. Plasmid pBP515 encodes kanamycin and gentamicin resistance and is transferable via mobilization by a pRP1-derived helper plasmid (pRP1H) to strains of several gram-negative species. After the introduction of pBP515, single-cell MICs (as measured by reduction of the viable cell count) of ciprofloxacin and nalidixic acid decreased by 4- to greater than 8,000-fold for all strains tested, and 8 of the 11 strains regained ciprofloxacin susceptibilities similar to those of the respective wild types. The results indicate that (i) high-level fluoroquinolone resistance in clinical isolates of E. coli, K. pneumoniae, P. aeruginosa, and A. calcoaceticus can result from mutational alteration of the gyrA gene, and (ii) gyrA mutations are involved in high levels of fluoroquinolone resistance in P. stuartii. Additional mutations outside the gyrA locus may contribute to resistance in K. pneumoniae and P. stuartii. PMID- 1759824 TI - Use of ampicillin-sulbactam for treatment of experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli K-1. AB - We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta lactamase-producing bacteria, against which the combination shows only moderate in vitro activity. PMID- 1759825 TI - Pharmacokinetics of cefuroxime axetil suspension in infants and children. AB - The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 micrograms/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including beta-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10- or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-verus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose. PMID- 1759826 TI - Antifungal activity of HWA-138 and amphotericin B in experimental systemic candidiasis. AB - HWA-138, a pentoxifylline analog, has been shown to increase yeast urinary clearance and to reduce yeast counts in the kidneys of rats infected with Candida albicans. Furthermore, HWA-138 has also been shown to prevent amphotericin B induced acute renal failure in rats. We report here on the effects of HWA-138 alone and in combination with amphotericin B in the treatment of systemic candidiasis in mice. When single doses of HWA-138 were administered intravenously (10, 25, or 50 mg/kg of body weight) into infected mice, no significant improvement in survival was observed. In infected mice treated intravenously with multiple doses of HWA-138 (10, 25, or 50 mg/kg once daily for 5 consecutive days), a significant increase in survival time was seen only in animals also receiving 25 mg of HWA-138 per kg (14 +/- 3 days test versus 9 +/- 1 days control; P less than 0.05). The coadministration of subtherapeutic doses of amphotericin B and HWA-138 resulted in increased survival time. Combination therapy with amphotericin B (0.1-mg/kg single dose) and HWA-138 (10-, 25-, or 50 mg/kg multiple doses) resulted in a significant increase in survival time over controls (19 +/- 4, 19 +/- 5, and 21 +/- 9 days, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P < 0.05). Variance analysis of these findings indicate synergistic activity between amphotericin B and HWA-138 in the treatment of experimental candidiasis in mice. PMID- 1759827 TI - Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime. AB - Single 2-g intravenous doses of ceftizoxime (CZX) and cefotaxime (CTX) were given over 30 min to 10 adult volunteers in a crossover manner on two separate occasions. Concentrations of CZX, CTX, and the primary metabolite of CTX, desacetylcefotaxime (dCTX), in serum, suction-induced-blister fluid, and urine were determined by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by using an extended least-squares modeling program (MKMODEL). CZX exhibited a half-life in serum (2.05 h) longer than that of CTX (1.43 h) but comparable to that of dCTX (2.02 h). The percentage of penetration in blister fluid, estimated by area under the curve ratios, was significantly higher for CZX (164.4%) than for CTX (60.8%). Serum bactericidal activity, determined for volunteer samples at 1, 6, 8, and 12 h after patients were dosed, against clinical isolates of the Bacteroides fragilis group, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Morganella morganii were significantly higher for CZX than those for CTX against members of the family Enterobacteriaceae at all times. Serum bactericidal titers against B. fragilis were also higher for CZX than for CTX at 1 h postinfusion. Neither CZX nor CTX exhibited any bactericidal activity at any other time against the B. fragilis group. In conclusion, the serum bactericidal activity of CZX was greater and more prolonged than that of CTX against tested strains in spite of the in vitro synergistic contribution of dCTX to CTX, equal serum elimination half-lives of dCTX and CZX, and similar antibacterial activity and similar instability under microbiological testing for CZX and CTX. PMID- 1759828 TI - Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. AB - The in vitro susceptibilities of 102 human campylobacter strains isolated between 1978 and 1980 and 100 strains isolated in 1990 to ciprofloxacin, norfloxacin, erythromycin, gentamicin, and doxycycline were examined. The biotypes and heat stable serotypes of the strains as well as antimicrobial treatments and travel history of the campylobacter-positive patients were also studied. The results indicated that susceptibility to erythromycin, gentamicin, and doxycycline has remained the same during the past 10 years. No gentamicin-resistant strains were found. Resistance to erythromycin was 3% in both groups of strains. However, the number of norfloxacin-resistant strains increased from 4 to 11% in the follow-up period, and ciprofloxacin-resistant strains, which had not occurred 10 years ago, composed 9% of the strains isolated in 1990. Thus, the increase of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli has been significant in Finland in the past 10 years. PMID- 1759829 TI - Shell-vial assay: evaluation of a new technique for determining antibiotic susceptibility, tested in 13 isolates of Coxiella burnetii. AB - Coxiella burnetii is a strictly intracellular bacterium. Bacteriostatic effects have been described previously on a few isolates in embryonated eggs (A. J. Spicer, M. G. Peacock, and J. C. Williams, p. 375-383, in W. Burgdorfer and R. L. Anacker, ed., Rickettsiae and rickettsial diseases, 1981). We used the shell-vial technique (D. Raoult, G. Vestris, and M. Enea, J. Clin. Microbiol. 28:2482-2484, 1990) to determine the susceptibility of C. burnetii to amoxicillin, amikacin, erythromycin, co-trimoxazole, pefloxacin, ofloxacin, ciprofloxacin, chloramphenicol, tetracycline, doxycycline, minocycline, and rifampin antibiotics at a single dilution. Human embryonic lung fibroblast monolayers in shell vials were seeded with 13 different C. burnetii isolates, including 3 reference strains (Nine Mile, Q212, and Priscilla) and 10 new isolates, in order to obtain 30% infected cells 6 days later. After inoculation, antibiotics were added, shell vials were incubated for 7 days, and immunofluorescence was revealed and compared with that of the positive controls. Strain Nine Mile was more susceptible than strains Q212 and Priscilla were. The heterogeneity of susceptibility to fluoroquinolones, chloramphenicol, and erythromycin was noted among the strains; all were resistant to amoxicillin and amikacin, and all were susceptible to rifampin, co-trimoxazole, tetracycline, and tetracycline analogs. PMID- 1759830 TI - Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children. AB - Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and CFB elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of CFB disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1 +/- 1.1 ml/min/kg) than in children > 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a finding different from preliminary data for adults. PMID- 1759831 TI - Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding. AB - The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD. PMID- 1759832 TI - Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers. AB - The pharmacokinetics of ampicillin-sulbactam in elderly subjects (65 to 85 years; group 3, n = 8), compared with those in middle-aged (41 to 64 years; group 2, n = 8) and younger (20 to 40 years; group 1, n = 8) subjects, were investigated. A single 2-g dose of ampicillin combined with 1 g of sulbactam in 60 ml of intravenous solution was administered to each subject over a 30-min period. Blood and urine samples were taken at baseline and serially over an 8.5-h period following the infusion. Ampicillin and sulbactam concentrations were assayed by high-performance liquid chromatography on a reversed-phase C-8 column. The mean levels in serum of both ampicillin and sulbactam were significantly higher for samples from group 3: for ampicillin from 1 through 8.5 h, and for sulbactam for the same time interval except at 5.5 h (P less than or equal to 0.05). The mean urinary excretion of both ampicillin and sulbactam was lowest, and urinary concentrations were highest in group 3. The areas under the serum drug concentration-time curve, the half-lives, and the maximum concentrations in serum were greatest, while the total clearance was lowest, for group 3 for both ampicillin and sulbactam. These results are consistent with a prolongation of antimicrobial activity of ampicillin-sulbactam in the elderly compared with that in younger subjects. PMID- 1759833 TI - Effects of two cations on gastrointestinal absorption of ofloxacin. AB - A study was performed to establish the effect of Al3+ and Fe2+ cations on the absorption of ofloxacin when it is administered orally at a dose of 200 mg. The study was carried out with nine volunteers, who each received three treatments (A [200 mg of ofloxacin], B [200 mg of ofloxacin plus 11 g of colloidal aluminum phosphate], and C [200 mg of ofloxacin plus 1,050 mg of FeSO4]) according to a Latin square design; the washout period was 1 week. The analytical technique was a microbiological diffusion method. The pharmacokinetic parameters were calculated from the cumulative urinary excretion data and from a sigma-minus plot. The total amount of ofloxacin excreted in urine had a mean value of 163.59 +/- 22.13 mg when ofloxacin was administered alone, 152.41 +/- 18.76 mg when it was administered with Al3+, and 146.49 +/- 14.85 mg when it was administered with Fe2+. No statistically significant differences were found in the F values (fractions of dose absorbed) obtained with ofloxacin alone and ofloxacin plus Al3+ (P = 0.341). When ofloxacin alone was compared with joint administration with Fe2+ the value of F decreased 10.85%; this difference is statistically significant (P = 2.623 x 10(-2)). PMID- 1759834 TI - Enantioselective disposition of ofloxacin in humans. AB - The enantioselective disposition of ofloxacin (OFLX) was studied in healthy subjects after oral administration of (+/-)-OFLX at a dose of 200 mg. S-(-)-OFLX and R-(+)-OFLX concentrations in serum and urine were measured separately by high performance liquid chromatography, and various pharmacokinetic parameters were calculated from the data. The ratio of S-(-) to R-(+) enantiomer concentrations in serum showed a increase with time, with S/R ratios of 1.01 at 2 h and 1.31 at 24 h. The terminal elimination half-life of S-(-)-OFLX was 6.9 h, which was significantly greater (P less than 0.05) than that of the R-(+) enantiomer (6.3 h). S-(-)-OFLX also revealed a significantly greater area under the concentration time curve in serum, mean residence time, and total body clearance than the R-(+) enantiomer did. The renal clearance of S-(-)-OFLX (7.14 liters/h/1.73 m2) was significantly lower than that of the R-(+) enantiomer (7.53 liters/h/1.73 m2). Although the difference in the pharmacokinetic parameters of the enantiomers was small, their disposition in humans was found to be stereoselective. The difference between the enantiomers may be explained by the difference in their renal excretion. PMID- 1759835 TI - Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers. AB - Pharmacokinetic and pharmacodynamic interactions between Org 10172 (intravenous bolus injection of 3,250 anti-Xa units), which is a low-molecular-weight heparinoid, cloxacillin (500 mg orally four times daily for 3 days), and ticarcillin (4,000 mg intravenously four times daily for 2 days) were evaluated in two separate studies with healthy male volunteers (n = 18). Both cloxacillin and ticarcillin caused a significant increase in elimination half-life of anti-Xa activity, i.e., from 31 +/- 10 to 54 +/- 23 h and from 27 +/- 6 to 42 +/- 13 h, respectively (P less than 0.05). Ticarcillin decreased clearance (11%) and increased apparent volume of distribution (35%) (P less than 0.05), while for cloxacillin, these differences did not reach statistical significance. These changes in disposition of Org 10172 by the penicillins were not accompanied by important pharmacodynamic changes as evaluated by coagulation tests, platelet aggregation, and bleeding time. Cloxacillin appeared to influence blood coagulation (prolongation of the activated partial thromboplastin time and shortening of thrombin time; P less than 0.05) and facilitated thrombin-induced platelet aggregation, which coincided with a shorter bleeding time during the combined treatment in comparison with the time during treatment with Org 10172 alone (P less than 0.05). In conclusion, the disposition of Org 10172 was slightly changed by cloxacillin and ticarcillin, and, unexpectedly, cloxacillin appeared to have mild procoagulant effects. PMID- 1759836 TI - Treatment of murine invasive candidiasis with amphotericin B and cilofungin: evidence for enhanced activity with combination therapy. AB - The in vivo interactions of cilofungin, an echinocandin antifungal agent, and amphotericin B, a polyene derivative, in a murine model of disseminated candidiasis have been investigated. While single therapy with either drug alone prolonged survival of infected mice, kidney colony counts were not appreciably reduced. In contrast, combination therapy, especially at higher doses of both drugs, resulted in significant prolongation of survival and suppression of growth of yeast cells in the kidneys. Combination therapy of experimental candidiasis with cilofungin and amphotericin B did not result in antagonism; rather, additive or synergistic effects were seen. Future preclinical work with other echinocandin and polyene derivatives should include studies evaluating the in vivo interactions of both classes of compounds. PMID- 1759837 TI - Bacterial and fungal killing by iontophoresis with long-lived electrodes. AB - Iontophoresis with gold, carbon, and platinum electrodes was shown to effectively reduce or eliminate gram-positive, gram-negative, and Candida albicans inocula in synthetic urine. Platinum and gold electrodes were more effective than carbon electrodes, but platinum showed the best longevity and may reduce or eliminate microbial colonization of catheters. PMID- 1759838 TI - Susceptibility of Staphylococcus species and subspecies to fleroxacin. AB - Twenty-four Staphylococcus species or subspecies were examined for their susceptibilities to the fluoroquinolone fleroxacin (Ro 23-6240) by disk diffusion (5-micrograms disk) and by agar dilution for the determination of MICs. Resistant strains were further tested for their susceptibilities to oxacillin and the fluoroquinolone ciprofloxacin. Reference strains of the novobiocin-resistant species (Staphylococcus saprophyticus, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus arlettae, and Staphylococcus gallinarum) had an intrinsic intermediate susceptibility (MIC, 4 micrograms/ml) to fleroxacin. Fleroxacin resistance was not observed in the reference strains of the novobiocin susceptible species (MIC, 0.5 to 2.0 micrograms/ml). Clinical isolates of coagulase-negative species were generally less susceptible to fleroxacin than were reference strains. Seven percent of the Staphylococcus epidermidis clinical strains were resistant (MIC, greater than or equal to 8 micrograms/ml) to fleroxacin. Of these strains, 77% were resistant to oxacillin and 50% were resistant to ciprofloxacin. Thirty-four percent of the Staphylococcus haemolyticus clinical strains were resistant to fleroxacin, and 9% had intermediate susceptibility. Of the resistant strains, 95% were resistant to oxacillin and 77% were resistant to ciprofloxacin, while 23% had intermediate susceptibility to ciprofloxacin. Fleroxacin is an effective antimicrobial agent against most staphylococci. PMID- 1759839 TI - In vitro activity of 79 antimicrobial agents against Corynebacterium group D2. AB - Corynebacterium group D2 (CGD2) is involved in urinary tract infections in patients with underlying predisposing factors. This microorganism is highly resistant to a number of antimicrobial agents. We tested the activities of 79 antimicrobial agents against CGD2. beta-Lactams, aminoglycosides, and macrolides were ineffective. Fluorinated quinolones showed irregular activities, ofloxacin being the most active one. Doxycycline, rifampin, and mainly glycopeptides (vancomycin and teicoplanin) were the most active antibiotics against CGD2. PMID- 1759840 TI - Comparative efficacies of amphotericin B lipid complex and amphotericin B deoxycholate suspension against murine blastomycosis. AB - Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001). Fungizone was more effective than lipid complex at doses of 0.8 mg/kg of body weight. However, lipid complex at 12.8 mg/kg was not toxic and superior in efficacy (P less than 0.001) to 2.0 mg of Fungizone per kg (a toxic dose), and it cleared all animals of infection. Lipid complex is an effective therapy for murine blastomycosis. PMID- 1759841 TI - Ofloxacin penetration into tuberculous pleural effusion. AB - After 3 days of treatment with ofloxacin (300 mg given orally once daily), the drug levels in serum and pleural fluid 2 and 4 h after drug administration in patients with tuberculous pleural effusion were assessed by a rapid high performance liquid chromatography assay. The levels in serum (mean +/- standard error of the mean [SEM]) were 4.70 +/- 0.14 and 4.63 +/- 0.09 mg/liter 2 and 4 h after administration, respectively, and the levels in pleural fluid (mean +/- SEM) were 3.82 +/- 0.09 and 4.21 +/- 0.08 mg/liter, respectively. The pleural fluid-to-serum ofloxacin ratio at 2 h was 0.82 +/- 0.02 (mean +/- SEM), and the ratio at 4 h was 0.92 +/- 0.02 (mean +/- SEM). This study demonstrated very good penetration of ofloxacin into pleural fluid in tuberculous pleuritis. PMID- 1759842 TI - Aminoglycosides modify the in vitro metachromatic reaction and murine generalized Shwartzman phenomenon induced by Salmonella minnesota R595 lipopolysaccharide. AB - Endotoxin-neutralizing activity may be an important property for antibiotics to be used in severe sepsis. Several antibiotics, belonging to different classes, were evaluated as to their endotoxin-neutralizing ability, using the inhibition of an in vitro metachromatic assay for lipopolysaccharides and a murine generalized Shwartzman reaction model. Gentamicin, amikacin, and sisomicin have been found to share significant in vitro antiendotoxin activity at an antibiotic/endotoxin ratio as low as 1.0/5 (by weight) and to reduce the murine generalized Shwartzman reaction at an antibiotic/endotoxin ratio of 3.3/5. PMID- 1759843 TI - Role of exposure mode in the bioavailability of triphenyl phosphate to aquatic organisms. AB - A laboratory study was conducted to investigate the role of the route of triphenyl phosphate (TPP) entry on its aquatic bioavailability and acute biological effects. Three TPP treatments were used for exposures of fish and invertebrates. These consisted of TPP dosed directly into water with and without clean sediment and TPP spiked onto sediment prior to aqueous exposures. Results of static acute toxicity tests (no sediment) were 0.78 mg/L (96-h LC50) for bluegill, 0.36 mg/L (48-h EC50) for midge, and 0.25 mg/L (96-h EC50) for scud. At 24 h, the sediment (1.1% organic carbon)/water partition coefficient (Kp) for TPP was 112. Use of this partition coefficient model to predict the sediment-mediated reduction of TPP concentration in water during toxicity tests resulted in a value that was only 10% less than the nominal value. However, the required nominal concentration of TPP to cause acute toxicity responses in test organisms was significantly higher than the predicted value by the model for both clay and soil derived sediment. Direct spiking of TPP to soil minimized TPP bioavailability. Data from parallel experiments designed to track TPP residues in water through time suggest that sorption kinetics control residue bioavailability in the initial 24 h of exposure and may account for observed differences in LC50 and EC50 values from the sediment treatments. PMID- 1759844 TI - Environmental contaminants and biochemical responses in flatfish from the Hvaler Archipelago in Norway. AB - The levels of several environmental contaminants, including selected polyaromatic hydrocarbons (PAH), organochlorines (DDT/DDE, hexachlorobenzene), 15 polychlorinated biphenyl (PCB) congeners, and polychlorinated dibenzofurans and dibenzo-p-dioxins, PCDF/PCDD), and heavy metals (Cd, Hg, Pb, and As) were analyzed in muscle and liver of three different flatfish species (dab, Limanda limanda; flounder, Platichthys flesus; plaice, Pleuronectes platessa) caught by gill netting at different sites in the Hvaler Archipelago. Indices of biochemical effects in liver S9-fractions were studied by measuring cytochrome P450-dependent monooxygenase and UDP-glucuronyl transferase activities, and by immunoquantitating cytochrome P450 1A1 using an indirect enzyme-linked immunosorbent assay (ELISA). Only low levels of PCDD/PCDF, Cd, and Pb were observed, whereas PCB levels were significantly elevated in fish from the inner sites of the Archipelago compared to a reference site. The contaminant gradient toward the Glomma estuary was correlated with increased cytochrome P450 1A1 activity, measured as 7-ethoxyresorufin O-deethylase (EROD), and with immunoquantitated P450 1A1. In contrast, fish from the site at Idefjorden, although containing elevated contaminant levels, did not show elevated EROD activity, but apparently elevated P450 1A1 protein. These findings may reflect different pollution histories of the sites, and indicate the applicability of biochemical effect indices (i.e., EROD and P450 1A1 immunoquantitation) to monitoring studies. The integrated chemical-biochemical approach employed in this study can obviously be expanded to give fruitful information about cause-effect relationships in other contaminant situations. PMID- 1759845 TI - A field study on stress indices in the sea mussel, Mytilus edulis: application of the "stress approach" in biomonitoring. AB - Sea mussels, Mytilus edulis, collected from a relatively unpolluted area of the Eastern Scheldt, were transplanted along contaminated sites of the Western Scheldt for 2 1/2 and 5 months. Several established stress indices were determined such as accumulation of pollutants, adenylate energy charge (AEC), and condition index. Following field exposure, mussels were also subjected to an additional lethal or sublethal stress. The data show that environmental exposure alters the mussel's response to stress, viz., aerial exposure and increased temperature, at the organismal (anoxic survival time), biochemical (AEC), and molecular (heat shock protein synthesis) level. The "stress approach" to assessment of environmental contamination appears to be a promising method to disclose early changes in the organism at a stage when conventional parameters (condition index, AEC) remain still unchanged. PMID- 1759846 TI - Biochemical alterations in fish fingerlings (Cyprinus carpio) exposed to sublethal concentration of linear alkyl benzene sulphonate. AB - Fish fingerlings (Cyprinus carpio) were exposed to sublethal concentrations of linear alkyl benzene sulphonate (0.005 ppm) for 24, 48, and 96 h under static laboratory conditions. Alterations were noted in the levels of glycogen, lactic acid, sialic acid, and acid and alkaline phosphatases in the gill, liver, and kidney. This chemical may impair metabolic processes in fingerling carp, because increased exposure resulted in significant increases in lactic acid and decreases in glycogen and sialic acid along with inhibition of acid and alkaline phosphatase activity. PMID- 1759847 TI - Chronic toxicity of dietary disodium arsenate heptahydrate to juvenile rainbow trout (Oncorhynchus mykiss). AB - Juvenile rainbow trout were fed semi-purified diets containing graded levels of disodium arsenate heptahydrate (DSA) for 12-24 weeks under standard laboratory conditions to define the maximum acceptable toxicant concentration (MATC) and to correlate signs of toxicity with diet and tissue arsenic concentrations. The MATC for DSA was between 13 and 33 micrograms As/g diet or 0.281-0.525 mg As/kg body weight/day. The most sensitive and reliable indicator of chronic dietary DSA toxicity in rainbow trout was chronic inflammation of the gallbladder wall. Chronic inflammatory changes in the sub-epithelial tissues of the gallbladder wall were evident in 71% of rainbow trout exposed to 33 micrograms As/g diet for 24 weeks, and 100% of rainbow trout exposed to 65 micrograms As/g diet for 24 weeks or 49 micrograms As/g diet for 12 weeks. No fish exposed to 13 micrograms As/g diet or less for up to 24 weeks showed any demonstrable gallbladder lesions or any other ill effect of arsenic exposure. Other signs of chronic dietary DSA toxicity to rainbow trout included decreased growth rate, mild to moderate anemia, and, at higher levels of exposure, active feed refusal leading to decreased feed consumption. Mild nephrocalcinosis was noted in one experiment where kidney arsenic residues exceeded 14 micrograms As/g tissue dry weight. PMID- 1759848 TI - Time course reversibility of liver and blood changes induced in weanling rats after polychlorinated biphenyl exposure during lactation. AB - Phenoclor DP5 (DP5), a mixture of polychlorinated biphenyls (PCBs), was administered to lactating rat dams, every two days from postnatal days 2 to 20, at 50 mg/kg of body weight. Resulting effects on tissue concentrations of PCBs and on liver lipids, nucleic acids (DNA and RNA), proteins and blood lipids of offspring, at different times after weaning, until postnatal day 100, were studied. On postnatal day 21, DP5 contents found in liver, brain and fat of young rats indicated that a great part of the dam's body stores of PCBs was eliminated into the milk. These accumulations were related to an increase of relative liver weight, a decrease in DNA concentration and a rise in liver RNA, protein and phospholipid levels, indicating an inducing effect of DP5 in weanling rat. Changes in lipid metabolism were associated with increases of liver triacylglycerol and cholesterol and decrease of blood triacylglycerol. Both sexes exhibited an identical responsiveness to PCBs. The biochemical alterations observed in liver and blood at weaning, disappeared with time and were no longer detectable after postnatal day 40 in both sexes. Relative liver weight increase persisted until postnatal day 60 in males and postnatal day 100 in females. Residual aspects of alterations induced before weaning, by exposure via milk, could persist until postnatal day 100. Permanent effects of PCBs, after perinatal exposure could be assessed in later life of rats, when PCBs were almost completely cleared from body tissues. PMID- 1759849 TI - Lead toxicosis in tundra swans near a mining and smelting complex in northern Idaho. AB - Die-offs of waterfowl have occurred in the Coeur d'Alene River system in northern Idaho since at least the early 1900's. We investigated causes of mortality and lead and cadmium contamination of 46 tundra swans (Cygnus columbianus) from 1987 to 1989; an additional 22 swans found dead in 1990 were not examined. We necropsied 43 of the 46 birds found from 1987 to 1989; 38 of these were from the Coeur d'Alene River system, which has been contaminated with mining and smelting wastes for a century, and the other 5 were from a nearby, relatively uncontaminated area. Of the 36 livers of swans from the contaminated area that were analyzed, 32 contained lethal levels of lead (6 to 40 micrograms/g, wet weight) and all birds exhibited several symptoms of lead poisoning, notably enlarged gall bladders containing viscous, dark-green bile. Only 13% of the lead poisoned birds (10% when data were included from other studies of swans in the area) contained shot, compared to 95% of lead-poisoning swans in studies outside northern Idaho. Lead concentrations in blood samples from 16 apparently healthy swans (0.5 to 2.3 micrograms/g, and 4 lead-poisoned birds found moribund (1.3 to 9.6 micrograms/g) indicating that tundra swans accumulated high levels of lead from ingestion of sediment that contained up to 8,700 micrograms/g of lead and plants that contained up to 400 micrograms/g. The swans spend only a few weeks in the area staging during the spring migration. The five tundra swans from the uncontaminated area had low levels of lead and essentially no symptoms of lead poisoning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759850 TI - Metal pollution and its impact on algae in flowing waters in India. AB - Metal pollution in the river Godavari in India, due to discharges of liquid wastes from a paper mill, has been studied for a period of two years. At the discharge point and 1 km from the point of discharge, iron, manganese, and zinc were recorded in high concentrations, whereas cadmium and chromium were observed in low concentrations. No metal was in detectable concentration in water before the river receives the effluents. A considerable drop in pH values and an appreciable increase in organic matter, hardness, and calcium levels were noticed after entry of wastes. Diatoms were more diversified in fresh water, whereas cyanobacteria were more prevalent both qualitatively and quantitatively at the polluted stations. Mathematical equations involving heavy metals and physicochemical factors were drawn for better understanding of the distribution of algae. PMID- 1759851 TI - Toxicity of oleic acid anilide in rats. AB - In the present investigation, we have studied the toxic potential of oleic acid anilide (OAA) and heated oleic acid anilide (HOAA) in relation to the toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of OAA or HOAA in mineral oil by gavage, on alternate days for 2 weeks (total 7 doses). The control rats received an equal volume of mineral oil only. The animals were sacrificed at days 1, 7, and 28 following the last dose. Ratio of organ-to-body weight showed increases in spleen and kidney of HOAA and OAA treated rats, respectively, at day 1 while this ratio for liver in HOAA treated group showed a decrease at day 1. Among blood parameters, white blood cells increased in HOAA treated group at day 1 and in both OAA and HOAA groups at day 28. Mean corpuscular hemoglobin (MCH) and mean cell volume (MCV) also showed increases in the HOAA treated rats at days 7 and 28. Serum lactate dehydrogenase (LDH) decreased in both OAA and HOAA treated rats at day 1, while at day 7 the decrease was confined only to the HOAA group. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities also decreased at most of the time points. Liver mitochondrial ATPase activity decreased in the HOAA group at day 7 and in the OAA group at day 28. Among serum immunoglobulins, IgA levels increased throughout the study but the changes were more pronounced in HOAA treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759852 TI - Pesticide and polychlorinated biphenyl residues in waters at the mouth of the Grand, Saugeen, and Thames Rivers, Ontario, Canada, 1986-1990. AB - Water samples were collected from the mouths of the three major agricultural watersheds, the Grand, the Saugeen, and the Thames (Ontario, Canada), between January 1986 and December 1990. Analyses were performed for 18 herbicides, 26 insecticides, and 4 fungicides in use in the basins. A total of between 425 and 474 samples were analyzed for each of the major groups of pesticides. Six herbicides, two insecticides and polychlorinated biphenyls (PCBs) were identified in surface water. Atrazine and its metabolite desethylatrazine were the most frequently found pesticide present in 340 of 474 samples or 72%; the metabolite was not always present with the parent compound. The second most frequently found pesticide was metolachlor which was identified in 30 of 474 samples or 6.3%. 2,4 D and cyanazine were present in 3.3% and 1.5% of the samples, respectively; alachlor, mecoprop, and simazine were present in 0.5% of the samples. Dicamba and metribuzin were present in single samples (0.2%). DDT, heptachlor epoxide, and PCB were identified in only single samples over the 5-year period. Between 342 and 2959 kg/annum of total atrazine were found passing the mouth of the three rivers and entering Lakes Erie or St. Clair between 1986 and 1990. The greatest loss was from the Thames River and the least from the Saugeen River. Between 1% and 2% of that applied in the watershed was lost at the mouth. Loadings of only two other pesticides to the rivers exceeded 5 kg in any one year, namely, metolachlor and 2,4-D. In the case of metolachlor, loadings ranged from less than 5 to 1,726 kg/annum, the highest being in the Thames and the lowest in the Saugeen River. 2,4-D exceeded a loading of 5 kg/annum in 1988 in the Grand River. Atrazine, cyanazine, and metolachlor were tracked across Lake St. Clair from the mouth of the Thames to the mouth of the Detroit River in 1987. PMID- 1759853 TI - Residues of pentachlorophenol and other chlorinated contaminants in human tissues: analysis by electron capture gas chromatography and electron capture negative ion mass spectrometry. AB - Samples of human tissues including testes, kidneys, prostate glands, livers, and adipose tissues removed at autopsy were analyzed for pentachlorophenol (PCP) and nonachloro-2-phenoxyphenol (NCPP); the fat samples were also analyzed for other chlorinated contaminants. Electron capture gas chromatography was used to quantitate the residues after isolation and cleanup. Identity of the residues was confirmed by electron capture negative ion mass spectrometry. All tissues analyzed for PCP tested positive with a range from 0.007 ppm (microgram/g) in subcutaneous fat to 4.14 ppm in testis. Residues of NCPP were much lower, ranging from levels below the detection limit to 0.59 ppm in testis. The highest average residues, based on the lipid content of the tissue, of PCP (1.09 ppm) and of NCPP (0.19 ppm) were found in testis followed by kidney (0.95 ppm PCP), prostate (0.84 ppm PCP), and liver (0.59 ppm PCP). Residues of these chemicals in the adipose tissues were on the average about 40 times lower than the residues in the non fatty tissues. Other chlorinated contaminants found in the subcutaneous fat included hexa-, hepta-, and octa-chlorodibenzo-p-dioxins at sub-ppb levels and DDE averaging 2.47 ppm. PMID- 1759854 TI - Evaluation of the effects of chelation therapy with time following strontium exposure to mice. AB - The effect of increasing the time interval between strontium exposure and chelation therapy was studied in male Swiss mice. Diethylenetriaminepentaacetic acid (DTPA), ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), 4,7,13,16,21,24-hexaoxa-1,10-diazabycyclo[8.8.8]-hexacosane (Kryptofix 222), tartaric acid, and 1,13-bis(8-chinolyl)-1,4,7,10,13-pentaoxatridecan (Kryptofix 5) were administered intraperitoneally at 0, 6, 12, and 24 h after subcutaneous injection of 1,139 mg/kg of strontium nitrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of strontium into urine and feces was determined for five days after which time the animals were killed, and the concentration of strontium was determined in various tissues. Only Kryptofix 222 was capable of increasing the total urinary elimination of strontium when given immediately after strontium exposure, whereas the amount of total strontium excreted into the feces was significantly enhanced by treatment with EGTA at 0 or 24 h after strontium injection, or with Kryptofix 222 at 6 h after strontium exposure. However, Kryptofix 222, tartaric acid, and Kryptofix 5 reduced the concentration of strontium in bone at 0, 6, or 12 h after strontium injection, whereas at 24 h only Kryptofix 5 significantly lowered the concentration of the metal in bone. The results of this study indicate that the length of time before initiating chelation therapy for strontium removal may influence remarkably the effectiveness of this therapy. PMID- 1759855 TI - Evaluation of potential interactions involving trichothecene mycotoxins using the chick embryotoxicity bioassay. AB - The Chick Embryotoxicity Screening Test (CHEST) was used to examine possible interactions between different trichothecenes. Combinations of deoxynivalenol (DON), 15-acetyldeoxynivalenol (15-ADON) and HT-2 toxin were tested at various concentrations and the effects were determined based on percent mortality. The combined toxicity of any two trichothecenes was found to be additive. Discrepancies between observed and expected mortality values seldom differed by more than 10%, well within sampling error for the binomial distribution. Several limitations of the CHEST assay are discussed. PMID- 1759856 TI - On partnerships. PMID- 1759857 TI - Institutionalization of an elderly family member: reactions of spouse and nonspouse caregivers. AB - Although a prevalent clinical assumption is that the caregiver well-being improves following patient institutionalization, recent research challenges this assumption. In this article, the impact of patient institutionalization on the well-being of family caregivers is examined. Caregiver reaction, sense of general well-being and level of depression are compared pre- and postinstitutionalization and differences between spouse, adult child, and other caregivers are investigated. PMID- 1759858 TI - A comparative study among college students of sexual abuse in childhood. AB - A disproportionate random sample (200 women, 400 men) of students attending a major university was invited to participate in a mailed survey to study differences in self-efficacy, coping, and well-being between men and women who were sexually abused in childhood and those who were not. A total of 271 students (111 women, 160 men) responded by returning the completed survey. Fifty percent of the women and 22% of the men in the sample reported one or more unwanted sexual experiences in childhood. Multivariate analysis of variance (MANOVA) techniques to analyze differences in self-efficacy, coping (confrontive, emotive, palliative), and well-being between women and men who reported childhood sexual abuse and those who did not showed significant interaction effects by sex for abuse (F = 2.609, P = .025, df 5,263) and significant effects by sex (F = 3.356, P = .006), but no significant differences for abuse alone. Univariate F tests were significant (F = 5.386, P = .021) for palliative coping with abused men reporting the highest scores, abused and nonabused women having the highest scores on emotive coping (F = 9.049, P = .003), and nonabused men and women having highest scores on well-being (F = 7.276, P = .007). A second MANOVA was performed on data from 245 students (nonabused and those who reported contact sexual abuse). Significant interaction effects by sex for abuse (F = 2.259, P = 0.49, df 5,237) and main effects for abuse (F = 3.225, P = .008) were found. Although abused men scored lowest on well-being, both abused men and abused women scored higher on emotive coping and lower on well-being than nonabused subjects. These are new findings with implications for developing and testing nursing interventions for this vulnerable group of young adults. PMID- 1759859 TI - Suicide: a conceptual model for an avoidable death. AB - Suicide as a premature exit from life is confusing not only for family and friends of the individual who shows suicidal behavior but also for many professionals. This article defines the concept of suicide, clarifies terms associated with suicide, reviews current clinical and research literature on suicide, and proposes a conceptual model that describes suicide as both an event and a process. PMID- 1759860 TI - Hiding and healing: resolving the suicide of a parent or sibling. AB - The purpose of this study was to describe the long-term effects of suicide of a parent or sibling during childhood or young adulthood. A grounded theory approach was used to discover the respondents' perceptions of the meaning of the event and the effects that it had on them. The themes that emerged from the data were experiencing the pain, hiding the pain, and healing the pain. The need to hide the pain often interfered with the process of healing the pain. Findings indicate that many survivors of suicide during childhood experience painful, unresolved grief that affects their well-being in adulthood. PMID- 1759861 TI - Seasonal affective disorder, Part I: A review of the neural mechanisms for psychosocial nurses. AB - This article is the first of a two-part series on Seasonal Affective Disorder (SAD). Mental health and nursing researchers are beginning to investigate the implications of seasons on mood and mood states. Delineation of SAD and its treatment by phototherapy is an example. This article reviews the pertinent research regarding the hypothesized neural mechanisms of SAD. Three competing hypothesis are contrasted and compared: the melatonin hypothesis, the phase delay hypothesis, and the photon counting hypothesis. Although no one theory is universally accepted, current data supports the phase delay hypothesis and suggests that morning phototherapy is the most effective treatment. PMID- 1759862 TI - Seasonal affective disorder, Part II: Phototherapy, an expanded role of the psychosocial nurse. AB - The integration of neurobiology into the research and practice of psychosocial nursing is an imperative for the decade of the 1990s. This substantial goal probably will be achieved through the completion of smaller endeavors. This article is intended to be one such contribution. The purpose of this article are threefold. First, it will introduce the psychosocial nurse to the characteristics of Seasonal Affective Disorder (SAD). This article also will provide the psychosocial nurse with the putative biological basis of SAD and phototherapy. Finally, specific information regarding the therapeutic application of bright light is provided. PMID- 1759863 TI - Biological correlates of panic disorder with agoraphobia: practice perspectives for nurses. AB - The literature on panic disorder is summarized with regard to epidemiological, environmental, cultural, psychological, family, and genetic factors. Laboratory provocation of anxiety is reviewed with emphasis on the noradrenergic model of panic from a biological perspective. Positron emission tomography results involving brain asymmetries in lactate-sensitive panic patients are discussed, as are the psychopharmacological agents currently effective in the treatment of panic disorder. It is suggested that psychiatric nurses base their clinical practice on a holistic understanding of treatment implications as they relate to an individual's broader functioning. Areas for future nursing research are also identified. PMID- 1759864 TI - A nursing challenge: adult-onset Tay-Sachs disease. AB - Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort. PMID- 1759865 TI - [Minimally invasive surgery]. PMID- 1759866 TI - [Minimally invasive surgery]. PMID- 1759867 TI - [Pyelo-ureteral syndrome: the impact of endo-urological techniques]. AB - The present article reports our experience with endopyelotomy, a technique we have performed at our hospital since 1985. Sixty-two patients comprise this series. Of these, 57 were evaluated more than 6 months after treatment (65 cases of ureteropelvic junction syndrome (UPJS); 26 were primary UPJS (success rate 81%) and 39 secondary UPJS (success rate 84.5%). The complication rate was low. Patients in whom endoscopic treatment had failed were submitted to open surgery with no particular difficulty. A comprehensive review of the literature highlighting the indications, techniques and results achieved with this procedure is performed. PMID- 1759868 TI - [Percutaneous surgery in renal lithiasis. Current indications]. AB - The indiscriminate use of extracorporeal shock waves in the treatment of urinary calculi has changed the place of percutaneous surgery in the treatment of renal lithiasis. The authors analyse current indications of PCN highlighting stone size. In their view, calculi greater than 2 cm warrant treatment by PCN since only 15-20% of patients are completely stone-free following a single session of ESWL. Attention is focussed on the staghorn calculus and the percutaneous approach. They describe the difficulty encountered in the fragmentation of the cystine calculus owing to its hardness and discuss the difficulties that may arise when using the percutaneous approach in patients with coexisting renoureteral conditions, in the treatment of lithiasis in children and in the obese patients. PMID- 1759869 TI - [Serous renal cysts: translumbar percutaneous resection]. AB - Twelve patients with giant renal serous cyst located superiorly, inferiorly or in the central zone underwent percutaneous resection. The symptoms that had prompted the operative procedure disappeared immediately post-operatively in all patients. To evaluate the efficacy of resection, a CT scan was obtained pre-operatively and at 3 months post-operatively. All 9 patients in whom complete removal of the cyst wall had been achieved revealed a completely normal renal morphology on the post operative scan with no evidence of cyst. In the remaining 3 patients in whom the cyst could only be partially resected, the postoperative scan revealed residual cystic cavity, although its size had markedly diminished. The technique utilized and the maneuvers that permit removal of the cyst wall without risk are described. The indications and the therapeutic alternatives are discussed. PMID- 1759870 TI - [Exploration of the intra-renal collecting system using flexible fibroscopy]. AB - 23 cases of flexible retrograde nephroscopy system for undiagnosed hematuria or filling defect are reviewed. The introduction was carried out by combining hydraulic dilation, rigid ureterorenoscopy and a working sheath. The indications were merely diagnostic (filling defects and/or haematuria). The success rate was very high (22 of 23). 9 cases of papillary tumors, 4 cases of small radiolucent stones and 1 case of papillary necrosis were diagnosed. In 8 cases no pathology was found. The complication rate was extremely low and the postoperative course was uneventful. Flexible instruments offer a very good chance to explore the intrarenal collecting system and transureteral nephroscopy through a 10.8 F flexible scope is a feasible and effective procedure. PMID- 1759871 TI - [Conservative endoscopic treatment of urothelial cystic dysplasia of the upper urinary tract]. AB - We highlight the importance of the new diagnostic possibilities afforded by ureterorenoscopy and nephroscopy in the differential diagnosis of single or multiple cystic dysplasia of the upper excretory tract. Moreover, endoscopic treatment was performed in the two cases reported herein. In the first case the biopsy procedure was also therapeutic and in the second case cyst removal resolved the ureteral obstruction. Because the disease is detected infrequently and because treatment may be required even less frequently, several technical solutions have been applied to assess efficacy and reliability. Diathermy coagulation has proved to be the safest, fastest and the most effective. Follow up has documented the absence of recurrence and good reepithelialization of the ureteral wall without progression to stricture. In those cases with single cyst, one-stage diathermy loop resection permits obtaining biopsy material and radical removal of the neoformation. PMID- 1759872 TI - [Ureteral stenosis. Endo-urologic treatment (dilatation). Experience with 43 cases]. AB - Stricture of the ureter has been traditionally treated by open surgical techniques that occasionally had to be performed not without risk to the patient owing to the presence of septic and associated uremic conditions that invariably had a negative influence on the outcome. With the advent of endourological techniques in the last decade, much has been published on endoscopic treatment of the different areas of the urinary tract. One of the fields where important developments have taken place is that relative to endourological treatment of ureteric strictures. Since we started our therapeutic protocol for our patients in 1983 to date, we have treated 43 patients by dilatation. Patient follow up ranging from 6 months to 6 1/2 years (mean follow up greater than 30 months) revealed good results were achieved in 76.74%. The complications have been scant, mortality nil, and patients have been able to resume social and occupational activities early. All the foregoing prompt us to consider this therapeutic modality as the treatment of choice. PMID- 1759873 TI - [Endoscopic ureterectomy]. AB - Endoscopic ureterectomy is a minimally invasive surgical technique indicated in cases warranting ureterectomy to complement extended nephrectomy for pyelocaliceal urothelial carcinoma. The results achieved are identical to those of conventional ureterectomy (open surgery) without the inconvenience or sequelae that usually present with the latter procedure. In 1982, the authors developed the modified Dell'Adami and Breda endoscopic ureterectomy technique. To date, they have performed their modified technique in 10 cases: 9 with infiltrating urothelial or highly malignant pyelic or caliceal tumor and 1 with diffuse leukoplasia and cholesteatoma of renal pelvis. The technique described herein permits intussusception of the ureter into the bladder by transurethral traction of a Chevassu ureteral catheter to which that cephalad end of the ureter is attached during the extended nephrectomy procedure. Once intussusception of the ureter has been achieved, a resectoscope is used to cut the ureter at the level of the ureteral meatus. Thereafter the mucosa of the corresponding trigonal horn is completely resected. The results are highly satisfactory in patients whose ureter has not previously been submitted to open surgery and is not compromised by tumor spread. PMID- 1759874 TI - [Endoscopic surgery of bladder diverticula]. AB - The most frequent method utilized in the treatment of bladder diverticula is by open surgery using the extravesical, transvesical or combined approach. The endoscopic techniques consisting of electrocoagulation of the diverticular mucosa alone (Orandi) or opening the diverticular neck by electroresection (Post-Vitale) constitute a therapeutic alternative not widely used to date. We have attempted to combine both techniques and, since 1985, we have treated 21 patients with bladder diverticula via the transurethral approach using the following technique: 1. The diverticular neck is opened wide by incision or electroresection. 2. Complete electrocoagulation of the diverticular mucosa. 3. Resolution of cervico urethral obstruction by cervico-prostatic incision or electroresection of the prostate. We have achieved good results and no complications have been observed. Reduction of the diverticulum was not achieved in only one case. In our view, failure was due to the fact that treatment of the diverticulum had not been combined with prostate resection which the patient refused. The technique is described and the indications and possible complications are discussed. The results achieved by the authors indicate that this technique should be used more widely. PMID- 1759875 TI - [Percutaneous endoscopic urethrocervicopexy]. AB - A minimally invasive surgical technique that remarkably simplifies the Stamey procedure is described herein. The technique shortens the operating time and achieves a success rate of over 80%. Thus, we believe this technique should be considered in the treatment of stress urinary incontinence in females. PMID- 1759876 TI - [Treatment of urinary stress incontinence using paraurethral injection of autologous fat]. AB - The authors present the late results (greater than 1 year) in the treatment of urinary incontinence in 15 women with stress urinary incontinence and 5 men with post-adenomectomy incontinence using endoscopic injection of autologous fat tissue obtained by microliposuction. Good results were achieved in 23% of the cases with stress urinary incontinence and in 0% of those with post-adenomectomy incontinence. Although the results are disappointing, they are not very different from those obtained with teflon injection. Furthermore, the technique is simple, has no complications and it costs very little to obtain the autologous graft material. A historical review of free fat grafting and injection of liposuction fatty tissue is performed and the hypotheses that have been put forward recently relative to the fate of the fat graft are discussed. PMID- 1759877 TI - [Total transurethral electroresection of carcinoma of the prostate]. AB - Transurethral resection of the prostatic carcinoma was performed here most completely at a time already when radical surgical prostatectomy was not a rather new procedure. The preliminary evaluation of 150 cases of all stages (T1-4) showed a 5 year survival rate of almost 80% with post-operative complications comparable to transurethral prostatectomy of the adenoma. PMID- 1759878 TI - [Acquired hydrocele in the adult: sclerotherapy]. AB - We report our experience in the treatment of hydrocele using sclerosant therapy in 50 patients with adult acquired hydrocele (AAH) or cord cyst (CC). The sclerosing agent utilized in all of the patients was quinacrine dihydrochloride (quinacrine) at a dose of 13.3 mg 50 cc aspirated volume. The results were assessed clinically, ultrasonographically and thermographically. The presence of multilocular cysts or incomplete aspiration of the liquid was the most frequent cause of failure. The results show a success rate of 85%; however, 18% required more than one treatment. PMID- 1759879 TI - [Transperitoneal percutaneous cholecystolithotomy]. AB - Transperitoneal percutaneous cholecystolithotomy is a surgical technique for gallstone removal in the otherwise healthy gallbladder. It is a one-stage, alternative surgical procedure to extracorporeal lithotripsy. ESWL treatment of gallstones permits preservation of the compromised organ but has not been reported to achieve the potential good results. We describe the principles of the technique--similar to that of percutaneous renal surgery--and highlight specific aspects in this condition. PMID- 1759880 TI - Hypoosmotic swelling test in patients with varicocele. AB - The hypoosmotic swelling test is a simple test for measuring the functional competence of human sperm membrane. Thirty-five patients with varicocele were assessed by hypoosmotic swelling test and the results were compared with those in patients with idiopathic infertility. Percentage of swollen sperm in varicocele tended to be lower than that in idiopathic infertility, especially in sperm concentration between 30 x 10(6)/mL and 40 x 10(6)/mL. Varicocele with sperm motility of 40% or more revealed lower percentage of swollen sperm than idiopathic infertility did. The results indicate that varicocele may particularly injure sperm membrane function because hypoosmotic swelling test is a test for measuring functional ability of human sperm membrane. The percentage of swollen sperm recovered after the operation earlier than did the other sperm parameters such as sperm concentration or motility, which indicates that impaired sperm membrane injury by varicocele is reversible. PMID- 1759881 TI - Detrimental effects of cryopreservation on the structural and functional integrity of the sperm membrane. AB - Many centers have been disappointed with the pregnancy rate following the insemination of cryopreserved-thawed sperm, despite the maintenance of an adequate motile density. The possibility exists that damage to the sperm membrane might occur despite preservation of other semen parameters. Simple measurements of structural integrity (viability) and functional integrity (hypoosmotic swelling test) were performed on thawed specimens. In each instance, both the viability and HOS scores were less than the critical 50% level. Specimens from three different commercial centers had very poor HOS and viability scores from two of the centers, and, though the scores were generally greater than or equal to 50% from the third center, this was achieved by eliminating 11 of 12 donors. Reducing the glycerol concentration from 12 to 7% and switching from Nunc vials to plastic embryo straws did not improve the poor sperm membrane tests. The possibility exists that if modification of the cryopreservation technique leads to improved HOS and viability scores, perhaps improved pregnancy results will be realized. PMID- 1759882 TI - Anomalies of centriolar derivatives manifest in spermatic flagella and respiratory cilia of the stallion. AB - Anomalies of centriolar derivatives were identified in ejaculates and testicular and tracheal biopsies of a sterile stallion, using light, scanning, and transmission electron microscopy. LM revealed that over half the sperm population had only a vestigial or no tail, while the rest had tails of variable length and shape. The vestigial tail was represented by its anlage, which was implanted on the nucleus and differentiated up to capitulum and collum stage. The stunted tail had an axoneme and its derivatives, but was short in all tail segments. Regardless of the tail length or shape, virtually all axonemes were devoid of the central tubular complex ("9 + 0" defect). Abnormal tail segmentation was associated with missing or defective flagellar sheaths and a profusion of extraneous dense fibers, which contributed to the knobby, bulbous, or lobuliform tail configurations. The gradient of flagellar anomalies seems associated with the inability of the distal centriole to implant on the plasmalemma, to produce the axoneme, or maintain its growth, and to induce the normal differentiation of periaxonemal structures. In contrast to sperm, the tracheal epithelium displayed moderate changes, which are manifest in circumscribed rarefaction of cilia, increased incidence of compound cilia, and disturbed orientation of cilia regarding the plane of central tubular complex. The tracheal cilia were free of "9 + 0" defect. PMID- 1759883 TI - Recovery of motile sperm using the osmolality-gradient technique. AB - A simple, effective method for collecting motile sperm from ejaculates is developed. One hundred semen samples were obtained from both fertile and infertile men. Following initial semen dilution (1: 1) to 4 mL in a hypoosmotic medium (210 mOsm/kg), the mixture was layered into the specially designed tube filled with 1 mL recovery medium in the bottom and 1 mL isolation medium in the second layer to form three discrete layers. During the next hour the highly motile sperm out-distanced the other seminal contents to reach the bottom of the tube. Compared with the parent ejaculates, the recovered specimens exhibited an increased percentage of motile sperm with significantly enhanced sperm velocity and linearity (p less than .001). This method isolated motile sperm with higher velocity than those obtained using the swim-up technique. PMID- 1759884 TI - Basic arginine esterase from human seminal plasma: purification and some properties. AB - Basic arginine esterase (amidase) with a specific activity of 3.2 mumol N-alpha tosyl-L-arginine methyl ester (Tos-Arg-Me) esterolysis per A280 was purified about 230-fold from a CM-cellulose absorbed preparation of human seminal plasma. The purified enzyme was a single band with an apparent molecular weight of 3.4 4.1 x 10(4). The amidolytic activity of this enzyme was suppressed by aprotinin, soybean trypsin inhibitor (SBTI), leupeptin, and antipain, while alpha 1 antitrypsin, ovomucoid trypsin inhibitor (OTI), EDTA, and chymostatin had no or weak effect. This enzyme hydrolyzed synthetic basic amino acid derivatives and N alpha-tosyl-glycyl-L-prolyl-arginine-p-nitroanilide (Tos-Gly-Pro-Arg-pNA) and N alpha-tert-butyloxycarbonyl-L-leucyl-L-prolyl-L-arginine-p-nitroanilid e (Boc-Leu Pro-Arg-pNA) were the best substrates. The enzymatic characteristics of present enzyme were clearly different from tissue kallikrein, acrosin, and seminin in human semen. PMID- 1759885 TI - [Value of medical expert assessment in legal decisions in the city of Ulm in the 18th century]. PMID- 1759886 TI - [Secondary combined suicide viewed by the wife]. AB - A 47-year-old man was found dead at the bottom of a wall outward the door of the cellar of his house. Preliminary physical examination at the scene of the death revealed a laceration of the scalp, an incised wound in front of the neck and several stab wounds in the left chest penetrating through the clothing. Questioned by the police his wife told that her husband who suffered from severe depression had inflicted the incised and the stab wounds himself, had made an unsuccessful attempt at self-strangulation and had finally jumped down from the wall beside the stairs declining to the cellar of their house. As the circumstances of the scenario were suspicious and as the pattern of injuries arose doubts concerning self-infliction homicide was taken into consideration as well. Autopsy showed additional hesitation marks adjacent to the left end of the incised wound in front of the neck. The stab wounds of the chest were restricted to the region of the heart and displayed only minimal penetration of the chest wall, findings characteristic of self-infliction. As a consequence the manner of death could be determined as prolonged suicide, and exact reconstruction was possible with the help of the wife's testimony. PMID- 1759887 TI - [3 fatalities after communal use of methamphetamine]. AB - Two young men and a 17-year-old girl gathered in order to take methamphetamine, the quantity of which remained unknown. After a short time one of the men died on the scene; the other man, who was alcoholized in addition to having taken methamphetamine, fell over a railing from a height of several metres and suffered severe injuries before dying. The girl, who left for home by taxi, collapsed and died in a hospital about 2 hours later. Methamphetamine was detected in the blood of all three people. The autopsy results and the toxicological findings are reported and discussed with reference to the literature data. PMID- 1759888 TI - [Smoking trials with mercury contaminated cigarettes. Studies of attempted poisoning]. AB - In the context with an attempted poisoning it was investigated, to which extent an intoxication can be caused by smoking cigarettes, which contain elementary mercury. With a smoking apparatus the effect of the amount (9 mg to 1.4 g) and of the distribution of the Hg within the cigarette on its concentration in the mainstream and sidestream smoke as well as in the ash and the filter was analytically determined. It follows from these experiments, that at a good distribution almost independently of the amount involved only up to 2 mg Hg per cigarette are inhalated with the mainstream smoke, whereas up to 97% are found in the sidestream smoke. In the ash and the filter only small amounts are detected. By comparison with cases described in literature it is shown, that a poisoning by such cigarettes is possible only after frequent smoking or by passive smoking via the sidestream smoke in small and badly aerated rooms. PMID- 1759889 TI - [Cocaine profiling. A method of comparative substance studies of illegal cocaine samples]. AB - Illegal cocaine were extracted in acidic medium. The extracts contain significant amounts of truxinic and truxillic acids. Successful comparism of cocaine out of different sources can be achieved by chromatographing trimethylsilyl- or dimethyl t.-butylsilyderivates. The application of the method Ist limited by the purity of the samples. PMID- 1759890 TI - [Postinfarction segmental asynergy: correction after angioplasty. Predictive value of exercise thallium scintigraphy]. AB - The aim of this study was twofold: to evaluate the frequency of reversibility of segmental post-subendocardial infarction asynergy after coronary angioplasty, and to test the predictive value of the redistribution phenomenon during stress Thallium scintigraphy with respect to the reversibility of segmental asynergy. The inclusion criteria for this study were: previous postsubendocardial myocardial ischaemia with residual resting or effort ischaemia documented with or without the Thallium test, segmented asynergy documented by quantitative analysis of the ventriculography, complete correction of coronary angioplasty of stenotic single or double vessel disease, a balanced coronary distribution or dominant left coronary in cases of lesion of the circumflex artery. Out of 254 consecutive angioplasty procedures 39 patients met these inclusion criteria. The location of the subendocardial infarct (SEI) was anterior in 17 cases and inferior in 22 cases. The study protocol included a Thallium scintigraphy from the 10th day after SEI, ventriculography 24 hours later, angioplasty and control ventriculography 24 hours after angioplasty. Comparison of the two ventriculographies opposed Group A (reversible asynergy) and Group B (irreversible asynergy) according to criteria defined in 15 normal subjects whose average regional ejection fraction (REF) was 0.53 +/- 0.11. This result enables definition of normal segmental motion if the REF greater than 0.30 (mean--2 SD); hypokinetic if the REF greater than 0.30 or akinetic if the REF less than 0.10 (mean--4 SD). An increase of REF of 0.15 (50% of the minimal normal value) allowed definition of reversibility of asynergy. By these criteria, 19 patients (48.7%) had reversible asynergy after PTCA; 20 had definitive asynergy (51.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759891 TI - [Effect of subvalvular disease on results of percutaneous mitral valvotomy]. AB - In order to study the results of percutaneous mitral valvuloplasty (PMV), subvalvular mitral disease was classified using: 1) the transthoracic echo score (0-4), 2) an index derived from left ventricular angiography defined as the ratio of the distance from the extremity of the papillary muscle and the mitral valve in systole and the distance between the beginning of the aortic root and the apex of the left ventricle in diastole. This index of subvalvular fibrosis could be measured in 80 out of our first 103 PMV performed without complication; the mitral surface are a increased from 1.1 +/- 0.4 to 2.2 +/- 0.8 cm2 (p less than 0.0001). After PMV, mitral regurgitation was observed or was aggravated in 28 patients (35%), by one grade in 25 and by more than one grade in 3. The overall echo score was 8.3 +/- 1.5 and that of subvalvular fibrosis was 2 +/- 0.6. The angiographic index of subvalvular fibrosis was 0.18 +/- 0.04. No correlation was observed between echo and angiographic appreciation of subvalvular fibrosis. Multivariate analyses were selected: 1) the overall echocardiographic score (r = 0.45, p less than 0.0001), but not the angiographic index of subvalvular fibrosis or echocardiographic score of subvalvular fibrosis, was predictive of increase of valve surface area; 2) the absence of mitral regurgitation before PMV (p less than 0.01) and an angiographic index of subvalvular fibrosis less than or equal to 0.15 (p less than 0.03) were predictive of increased mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759892 TI - [Silent ischemic heart diseases in patients with peripheral arterial diseases. Screening and 5-year prognosis in a population of 418 patients]. AB - Silent ischaemic heart disease was looked for by exercise stress testing in 418 patients with chronic obliterative arterial disease of the lower limbs with no clinical or electrocardiographic signs of myocardial ischaemia. In the initial work-up, 6.2% of patients had a positive exercise test and the results were suspect in 9.2% of patients. These patients were followed up for 5 years. There were 42 deaths (10%). The cause of death was cardiovascular in 53.7% of cases (myocardial infarction 40.4%) and malignant disease in 35.7%. During the 5 year follow-up, ischaemic heart disease present as angina pectoris or myocardial infarction in 115 cases (27.5%). Patients who had a positive exercise stress test initially had a particularly high death rate (23%) and developed clinical signs of coronary insufficiency in 57.5% of cases. On the other hand, the peripheral vascular complications were relatively rare in this series: cerebrovascular accidents: 1.4%; retinal vascular accident: 1.1%; carotid surgery: 1.6%; lower limb amputation: 1.9%; lower limb vascular surgery: 17.7%. Silent ischaemic heart disease is very prevalent in patients with obliterative arterial disease of the lower limbs and is a main vital prognostic factor in these patients. These results confirm the need for a complete cardiovascular check-up in all patients with peripheral arterial disease. PMID- 1759893 TI - [Value of a new fast CK-MB determination for the diagnosis of myocardial infarction during the 1st hours. Preliminary study]. AB - This study evaluated the time for a new, rapid and reliable CK-MB analysis to become positive in myocardial infarction and compared it with classical total CK analyses. Serial analyses of total CK and CK-MB were performed in 49 consecutive patients referred to the Coronary Care Unit for suspected acute myocardial infarction. Twenty of these patients had myocardial infarction with rising enzyme levels, which enabled comparison of the precocity of one analysis compared to another. In these patients, the CK-MB analysis became positive on average 85 to 110 minutes before that of total CK. This result shows that CK-MB analysis can be a diagnostic sign of acute myocardial infarction at an earlier stage than the total CK analysis. The authors discuss the clinical value of this test in difficult indications of fibrinolytic therapy and underline that it enables a more objective assessment of the time of onset of necrosis than clinical data alone. PMID- 1759894 TI - [Mitral valve replacement in postinfarction mitral insufficiency. Immediate and long-term results apropos of a series of 39 surgically-treated patients]. AB - Thirty nine patients, mainly males (84.6%) with an average age of 66 years underwent mitral valve replacement for postinfarction mitral regurtation between March 1971 and December 1987. Twenty four were in Class IV of the NYHA Classification, 9 in Class III and 6 in Class II. All had a history of myocardial infarction predominantly of the inferior wall. The 33 preoperative coronary angiogrammes showed 13 patients with triple vessel disease, 15 with double vessel disease and 5 with single vessel disease. At operation, 13 patients had ruptured papillary muscles; acute dysfunction was observed in 16 and chronic in 10 patients. The hospital mortality was 36%; over three quarters of deaths were due to myocardial dysfunction. Twenty two patients had an associated myocardial revascularisation procedure with mitral valve replacement. All 25 survivors were followed up for an average of 2.3 years (94 patient-years). The 5 year actuarial survival (operative mortality included) was 55% and 77% of the 17 survivors are in Stages I or II of the NYHA Classification. The quality of these long-term results justifies surgery despite the high operative risk. PMID- 1759895 TI - [Programmed ventricular stimulation in unexplained syncope: risk factors for induction of ventricular tachycardia]. AB - The aim of this study was to identify the factors associated with the induction of ventricular tachycardia (TV) by programmed ventricular stimulation in patients with unexplained syncope. Sustained VT was induced in 71 out of 619 patients (11.5%) with syncope. A comparison of subjects with inducible VT and those without inducible VT showed underlying cardiac disease to be more common (89% versus 16%), more Holter abnormalities (Grade IVa ventricular extrasystoles) (60.5% versus 10%) in the first group but that signal-averaged ECG, recorded in 51 cases, was not sufficiently specific to differentiate the two groups (delayed potentials in 57% versus 43%). When syncope occurred in a subject without apparent cardiac disease with a normal Holter recording, inducible VT was rare (1%). On the other hand, when syncope was associated with cardiac disease and/or an abnormal Holter recording, VT could be induced in 45 to 64% of cases. In addition, as inducible VT was associated with severe infrahisian conduction defects in 3 cases, the following strategy is suggested in patients with unexplained syncope: programmed ventricular stimulation should be performed systematically during endocavitary electrophysiological investigation of AV conduction in patients with cardiac disease and if the non-invasive investigations, Holter monitoring or echocardiography, are abnormal. PMID- 1759896 TI - [Holter electrocardiography before and after coronary angioplasty. Angiographic correlation after 24 hours and 6 months]. AB - Myocardial ischaemia was searched for by Holter monitoring before and after coronary angioplasty with primary success in 31 patients. Control angiography was performed at 24 hours and 6 months after angioplasty. Twelve patients had signs of myocardial ischaemia before angioplasty (cumulated ischaemia: 743 minutes). The degree of coronary stenosis was 92 +/- 6% before angioplasty, 25 +/- 17% immediately after the dilatation increasing to 34 +/- 25% at the 24th hour (p less than 0.002). Despite successful angioplasty myocardial ischaemia persisted in 6 patients (cumulated ischaemia: 184 minutes) and was silent in 5 of the 6 cases. In these 6 cases, control angiography at 24 hours showed either a dissection (n = 4) or a filling defect (n = 2). The angiographic outcome of the postangioplasty stenosis and at 24 hours was the same in Group I without restenosis (25 +/- 14% versus 33 +/- 22%) as in Group II with restenosis (25 +/- 22% versus 37 +/- 30%). In Group I, the degradation of the result at 24 hours was reversible at 6 months (33 +/- 22% vs 23 +/- 14%). After angiographic success, postangioplasty ischaemia present in 20% of cases was frequently silent. No correlation was observed with restenosis at 6 months which raises the possibility of a reversible microthrombotic etiology. These results justify antiaggregant and anticoagulant therapy in the 48 hours following angioplasty. PMID- 1759897 TI - [Advantages and limits of programmed autologous transfusion in cardiovascular surgery. Apropos of 524 patients]. AB - Between October 1987 and July 1989, 544 patients, candidates for cardiovascular surgery, were included in a trial of programmed autologous autotransfusion. Five hundred and twenty four patients underwent one or several (maximum 4) blood donation sessions in the 3 weeks before surgery with no complications. Overall, 57% of patients benefited from homologous blood transfusion, thereby avoiding all risk of contamination. It was in the group of patients able to undergo 3 or 4 preoperative blood donations that we observed the smallest number of homologous transfusions (30%). Programmed autologous transfusion would seem to be a very useful technique for cardiac surgery, allowing a reduction in health care costs without additional patient risk. In order to improve on this method, it may be useful to associate a peroperative technique of blood recuperation in patients in whom the transfusion needs are likely to exceed the possibilities of preoperative blood donation alone. PMID- 1759898 TI - [Structure of arterial intima in children and adolescents. A pathological study of 101 cases]. AB - This was a macroscopic and histological study of the arteries of 101 unselected subjects from 0 to 20 years of age without cardiovascular pathology, autopsied to determine the cause of death at the medico-legal Institute of Paris. Stary's classification was used as a reference. Multiple Biopsies were taken from throughout the arterial system: initial aorta, carotid artery and its bifurcation, descending supra and infra renal aorta, iliac artery and left anterior descending artery. In this population, we found arterial lesions in 63% of subjects in the 15 to 20 year age range and this confirms previously reported data, especially by Stary. The lesions were identical irrespective of the site of biopsy and predominated at the bifurcations. No difference was observed with regards to sex and the lesions progressed after puberty. PMID- 1759899 TI - [Percutaneous transluminal angioplasty of the common trunk during the acute phase of myocardial infarction]. AB - The prognosis of cardiogenic shock in the acute phase of myocardial infarction has been transformed since the introduction of techniques of myocardial revascularisation. We report the case of a patient in cardiogenic shock after a large anterior myocardial infarct in whom failure of early thrombolytic therapy led to referral for emergency percutaneous transluminal coronary angioplasty. The success of the procedure on the patient's haemodynamic condition was life-saving. The originality of this case resides in the fact that revascularisation concerned the left main coronary stem. PMID- 1759900 TI - [Fortuitous discovery of the association of true and false aneurysm of the left ventricle after cardiogenic shock]. AB - The authors report the fortuitous diagnosis of a true and a false left ventricular aneurysm in a 77 year old man with severe ischaemic heart disease and calcific aortic stenosis, admitted for cardiogenic shock. The association of these two forms of aneurysm is very rare. Clinical and paraclinical diagnosis is difficult. Conventional left ventriculography is the investigation of reference but the diagnosis has been facilitated by Technetium 99 cardiac scintigraphy and color Doppler echocardiography. Surgery may be considered in cases of true aneurysm especially in patients with left ventricular failure, but the indication is formal in cases of false aneurysm. PMID- 1759901 TI - [Leiomyosarcoma of the right ventricle. Report of a case and review of the literature]. AB - Primary cardiac leiomyosarcoma is a very rare condition. Only 15 cases have been reported in the literature. We report the case of a 27 year old man admitted to hospital for chest pain in March 1985. Echocardiography showed a right ventricular tumour which was completely resected at surgery. The diagnosis of leiomyosarcoma was confirmed by histological examination. After 22 months follow up, the patient was still alive despite pulmonary metastases. The diagnosis of cardiac tumour used to be made post-mortem but since the introduction of new methods of investigation, especially 2D echocardiography, the diagnosis can be made at an early stage and allows rapid surgical resection, the only means of obtaining the histological diagnosis and of completely curing benign tumours. PMID- 1759902 TI - [Does corticosteroid therapy favor the development of ventricular aneurysm in myocardial sarcoidosis?]. PMID- 1759903 TI - Correlation between humoral immune responses and presence of virus in the CNS in dogs experimentally infected with canine distemper virus. AB - The role of the humoral immune response in clearance or prevention of canine distemper viral encephalitis of dogs infected with a virulent strain of canine distemper virus has been evaluated. Dogs that have demyelinating lesions, CDV proteins and infectious virus in their brains demonstrate an impaired humoral immune response. In dogs that recover from infection and contain no demyelinating lesions, viral proteins or infectious virus in the brain, antibodies to the internal proteins of CDV are observed early after infection. Later antibodies to primarily the H protein are detectable in sera of these dogs and the appearance of antibodies against the surface glycoprotein (H) correlates with the absence of lesions, CDV antigen and infectious virus in the brains of these dogs. Very late after infection immunoprecipitating antibody to all CDV antigens diminished rapidly so that at about ten weeks post infection antibodies that precipitate CDV antigens are barely detectable. PMID- 1759904 TI - Antigenic relationships among the 47 human adenoviruses determined in reference horse antisera. AB - Reference equine antisera to all 47 serotypes of human adenoviruses presently described have been prepared and evaluated by reciprocal neutralization and hemagglutination-inhibition tests. All tests were carried to endpoint dilutions a minimum of five times in each direction to give accurate values for homologous and heterologous antibody titers. Significant cross-reactions in the horse antisera were compared to similar data obtained from rabbit antisera. Using this analysis, major antigenic relationships exist among types 12-18-31 of subgenus A, types 7-11-14 and 34-35 of subgenus B, types 8-9-10, 10-19-37, 13-38-39, 15-22 42, 20-47, 24-32-33-46, and 29-45 of subgenus D, types 16-4 between subgenera B and E, and types 40-41 of subgenus F. Across all subgenera, types 8, 10, 13, 15, 17, 19, 26, 29, 39, 40, and 43 have antigenic moieties found most frequently in other types, averaging 12 heterologous reactions per type when summing both tests in both directions. Types 20, 30, 32, and 45 exhibit shared determinants slightly less often, with a mean of 8 heterologous reactions per type. PMID- 1759905 TI - Effect of polyions on the early events of Sindbis virus infection of Vero cells. AB - To clarify the role of electrostatic interactions in the binding of Sindbis virus (SNV) to cell membrane receptors, we investigated the effect of different polyions on the initial steps of infection of Vero cells by the virus. Several polyanions (mucin, heparin, polygalacturonic acid) and polycations (polylysine, protamine, polybrene) were able to reduce the replication of SNV when present in the viral adsorption period, whereas others (chondroitin sulfate, polymyxin B sulfate, histone) were devoid of any activity. Therefore the electric charge alone is not sufficient to explain the action of compounds. The effects of polyions on receptor binding, on bound virus, and on internalized virus have been examined. All the drugs inhibited SNV infection by affecting its binding to the cellular receptor. The results indicated that heparin and mucin act directly on the virus particle while polycations bind to the cell membrane receptor for the virus, protamine being effective on both targets. Since among polyanions glycosaminoglycans showed a strong inhibiting activity, the involvement of these molecules in the virus surface receptor was assessed by enzyme digestion of cell membrane with heparinase and chondroitin ABC lyase. PMID- 1759906 TI - Interleukin-2 enhances production in 24 hours of infectious human immunodeficiency virus type 1 in vitro by naturally infected mononuclear cells from seropositive donors. AB - When peripheral blood mononuclear cells from HIV-1 seropositive patients were treated with rIL-2 in vitro a rapid increase of 2-12 fold in production of extracellular infectious HIV-1 occurred, in 6 of 9 experiments. Overall, the increase in the 9 experiments was significant (p less than 0.01) and provides more direct evidence for an enhancing role of IL-2 in naturally infected cells. PMID- 1759907 TI - VP2 is the major exposed protein on orbiviruses. PMID- 1759908 TI - In memory of Victor Zhdanov. PMID- 1759909 TI - Synthesis and immunogenicity of hepatitis B virus envelope antigen expressed by recombinant vaccinia virus. Finding of retention signal in the C-terminal portion of the preS1 domain of subtype adyw. AB - Five different recombinant vaccinia viruses expressing the envelope antigen of hepatitis B virus (HBsAg) under the control of the P7.5 promoter were constructed. Cell cultures infected with some of the recombinant viruses synthesized both middle (M) and major surface (S) protein of HBsAg. It was shown that the length of the nontranslated sequence preceding preS2-ATG influenced the extracellular or intracellular HBV antigen distribution and the preS2:S antigen ratio. Some recombinants synthesized an M protein that was enlarged by additional 35 amino acids of preS1 domain and was entirely retained within the infected cells. Antibody responses to the S and preS2 antigens in mice revealed significant differences in the immunogenicity of individual recombinants. PMID- 1759910 TI - Transcriptional analysis of the bovine herpesvirus 1 Cooper isolate. Temporal analysis and characterization of immediate-early, early, and late RNA. AB - Blot hybridization analysis of infected bovine herpesvirus 1 (BHV-1) cellular RNA isolated at various times post infection and after treatment with specific metabolic inhibitors was used to characterize transcription of the BHV-1 Cooper isolate. Synthesis of BHV-1 RNA was detected as early as 3 h post infection and reached a maximum at six to eight hours post infection. The most transcriptionally active area of the genome was between map units 0.110 to 0.195, within the HindIII I fragment. From the entire genome a total of 59 transcripts ranging in size from approximately 0.6 to 10 kilobases were characterized as belonging to one of three distinct classes. Using the protein synthesis inhibitor cycloheximide, three immediate-early transcripts were identified as originating from the internal inverted repeat region between map units 0.734 and 0.842, corresponding to the HindIII D fragment. Using phosphonoacetic acid to prevent virus DNA synthesis by inhibition of the BHV-1 DNA polymerase, 28 early transcripts were recognized. The remaining 28 transcripts, classified as late RNA, were detected without the use of metabolic inhibitors at 6 to 8 h post infection. Transcription of early and late RNA was not restricted to any specific area of the genome. Eighty percent of the transcripts from both the HindIII A fragment, between map units 0.381 to 0.537 within the unique long segment, and the HindIII K fragment, between map units 0.840 to 0.907 of the unique short segment, were designated as belonging to the early class. PMID- 1759911 TI - Effect of an Autographa californica nuclear polyhedrosis virion component(s) on DNA synthesis and growth in several insect cell lines. AB - Thirteen different insect cell lines representing three different orders were infected with Autographa californica nuclear polyhedrosis virus (AcMNPV) whose genome had been inactivated in situ by photochemical means or by short wave UV irradiation. Changes in rates of cellular DNA synthesis, as measured by [3H]thymidine incorporation, and cell growth were subsequently measured at various times post infection. Seven cell lines exhibited a significant decline in [3H]thymidine incorporation (compared to control levels) during an initial 12 h period post infection, while three cell lines showed substantial declines in [3H]thymidine incorporation over a 4 day period post infection. All cell lines which showed a significant decline in [3H]thymidine over the duration of the experiment (4 days) also exhibited reduced cell growth rates. The role of a putative AcMNPV virion associated factor(s) in influencing these cellular events is discussed. PMID- 1759912 TI - Studies on the regulation of influenza virus RNA replication: a differential inhibition of the synthesis of vRNA segments in shift-up experiments with ts mutants. AB - The regulation of influenza virus vRNA synthesis in the course of the reproduction cycle was studied with the use of a series of ts mutants in shift-up experiments. The synthesis of vRNA segments was registered by means of polyacrylamide gel electrophoresis of nucleocapsid-associated RNA isolated from the infected cells labelled with [3H]uridine after the shift-up to a semi permissive temperature. Each mutant exhibited a specific differential pattern of vRNA synthesis inhibition after the shift-up. The most affected segments were either vRNA 4, vRNAs 4 and 7, or vRNAs 4, 6, and 7 in cells infected, respectively, with ts mutants C15 (ts lesion in PB1 gene), C45 (ts lesion in PA gene) and CmN3 (ts lesion in NS gene). The synthesis of vRNAs 1, 2, and 3 was relatively resistant to the shift-up in the cells infected with C15 or C45 and more sensitive in the cells infected with C44 (ts lesion in PB2 gene) or CmN3. The replication of the "early" genes (vRNAs 5 and 8) was generally least affected by the shift-up. The results are discussed in connection with the "early-late" transition of vRNA synthesis pattern in the course of infection. PMID- 1759913 TI - Lithium and hypercalcaemia. PMID- 1759914 TI - Asthma deaths: where are we now? PMID- 1759915 TI - Risk factors for death in patients admitted to hospital with asthma: a follow-up study. AB - Hospital records of patients with asthma admitted to teaching hospitals in Perth, Western Australia between 1976 and 1980 were examined retrospectively to identify characteristics of the illness which were associated with subsequent death. From 5722 admissions there were 195 deaths to December 1982, 186 of whom had records available (cases); 452 of the surviving subjects were used for comparison (controls). There was no difference in age of onset of asthma or cigarette smoking habits between the two groups, but ischaemic heart disease as an associated condition was significantly more frequent in cases. On admission to hospital an arterial PCO2 less than 45 mmHg was more frequent in those who died, but there were no differences in arterial PO2, lowest pH, highest or lowest FEV1 and FVC. Cases more frequently used home nebulisers and were more frequently prescribed corticosteroids, antibiotics and sedatives or tranquilizers prior to admission, corticosteroids and sedatives or tranquilisers during admission and sedatives or tranquilisers on discharge. These results suggest that cases had more severe asthma in that they were more often treated with home nebulisers, corticosteroids and antibiotics, but with the exception of PaCO2 the commonly used measurements of severity of asthma did not identify those at risk of death. The prescription of sedatives or tranquillisers appears to be associated with an increased risk of death in subjects with asthma. PMID- 1759916 TI - GM-CSF after allogeneic bone marrow transplantation: accelerated recovery of neutrophils, monocytes and lymphocytes. AB - Ten patients given HLA-identical sibling marrow transplants for lymphoid malignancy received recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) from day 7 to day 13 inclusive post transplant. Patients were prepared for transplantation with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. Immunosuppression to minimise the risk of graft-versus-host disease (GVHD) was cyclosporin/short methotrexate. Results were compared with a historical control group of patients (n = 16) given matched sibling transplants for acute leukaemia and receiving the same immune suppressive regime but not given GM-CSF. Recovery of total white cells, neutrophils, monocytes and lymphocytes was more rapid in the GM-CSF recipients (p less than 0.02). There was a suggestion of a decrease in non-viral infections in the first 30 days in the GM-CSF recipients (p = 0.09). There was, however, no significant difference in the severity of oropharyngeal mucositis nor in the duration of the transplant hospitalisation. Surprisingly, the severity of acute GVHD was higher in the GM-CSF recipients with six of eight evaluable patients having grade II-IV acute GVHD (p = 0.003). Two GM CSF recipients developed a fluid retention/capillary leak syndrome. These findings indicate a need for caution in the use of GM-CSF after allogeneic marrow transplantation. PMID- 1759917 TI - Low dose erythropoietin in maintenance haemodialysis: improvement in quality of life and reduction in true cost of haemodialysis. AB - Human recombinant erythropoietin (r-HuEPO) improves quality of life in patients on maintenance haemodialysis, but the haemoglobin (Hb) level necessary to achieve this improvement is unknown. In this study, quality of life, functional capacity and symptoms of 28 haemodialysis patients with an initial Hb of 67 +/- 2 (mean +/ SEM) g/L were assessed after 0, 6 and 12 months of r-HuEPO, the dose of which was titrated to achieve a stable Hb of between 90 and 100 g/L. At six and 12 months Hb was 97 +/- 2 and 93 +/- 2 g/L, and mean r-HuEPO dose between three and six, and between nine and 12 months was 88 +/- 6 and 62 +/- 9 U/kg/week intravenously respectively. There was a significant improvement in level of activity and satisfaction with various aspects of life, and a reduction in fatigue, weakness, dyspnoea, angina and restless legs. Patients were able to walk 50% further in six minutes. The improvement in quality of life and function was similar to that reported from other centres whose target Hb was between 100 and 120 g/L, and where the r-HuEPO dose was 75% higher than in this study. Costs of r HuEPO therapy were assessed. The drug itself costs +A3681/yr/patient, to which was added the estimated cost of additional dialyses and medications, bringing the total to +A5177/yr/patient. There was, however, a reduction in both hospitalisation by 8.3 days/yr/patient and medical consultation by 3.9 hours/yr/patient. Five patients commenced full-time work, one took up full-time study aimed at finding work, three transferred to home haemodialysis and six fewer patients drew social security benefits. The net cost saving from using low dose r-HuEPO was more than +A1,000/yr/patient. PMID- 1759918 TI - Dubbo study of the elderly: sociological and cardiovascular risk factors at entry. AB - A prospective study of elderly Australians commenced in 1988 in Dubbo, NSW. Its goals are to identify predictors of mortality, hospitalisation and placement in long-term care, with special focus on risk factors for cardiovascular disease. The study population were non-institutionalised subjects, comprising 1237 males and 1568 females 60 years and over. This report describes the baseline findings: demographic, educational and economic data; tobacco and alcohol usage, self medication and other habits; medical contacts and past diagnosis; prescribed medication and in study diagnosis; psychosocial variables, functional health and social support; blood lipid and lipoprotein data; blood pressure, spirometry and glucose data; heights and weights. Where comparison has been feasible, the findings in Dubbo closely resemble those obtained from the rest of Australia. The findings presented provide the basis for aetiological studies of future outcomes. PMID- 1759919 TI - Reproducibility of synovial fluid examination for crystals. AB - A quality assurance survey of synovial fluid examination for crystals was performed at six teaching hospitals. Aliquots of 12 different fluids (three with no crystals, one with betamethasone crystals, four with calcium pyrophosphate dihydrate (CPPD) crystals and four with monosodium urate monohydrate [urate] crystals) were examined by all six laboratories. Four laboratories performed well (10 or more correct out of 12) but two did poorly (50% or less correct). False positive crystal identification occurred in eight of 72 samples, but all false positive reports were from two laboratories. CPPD and urate crystals were missed in seven of 24 (29%) and five of 24 (21%) samples respectively. The standard of synovial fluid examination for crystals in Sydney teaching hospitals is not uniform and in some cases appears unsatisfactory. PMID- 1759920 TI - Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus. AB - The effects of metformin on glycaemia, insulin and c-peptide levels, hepatic glucose production and insulin sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1--no metformin for four weeks; stage 2--metformin 500mg mane; stage 3--metformin 500mg thrice daily; stage 4--metformin 1000mg thrice daily. Results are expressed as Mean +/- SEM. Fasting blood glucose decreased from basal values (9.7 +/- 1.0 mmol/L) by 13% at stage 2, 34% at stage 3 and 41% at stage 4 (p less than 0.02 vs basal for all stages; p less than 0.02 stage 2 vs stage 3). Post-prandial glycaemia was significantly improved only with metformin 3000mg/day (p less than 0.05). Fasting, meal-stimulated and total insulin and c-peptide levels showed no change. Hepatic glucose output did not change significantly with metformin. Insulin sensitivity, measured as total glucose utilisation during hyperinsulinaemia, increased from stage 1 (10.3 +/- 2.1 mumoL/kg/min) by 23% at stage 3 (p less than 0.05) and by 29% at stage 4 (p less than 0.02). Basal metabolic clearance of glucose increased compared to stage 1 (1.69 +/- 0.16 mL/kg/min) by 30% at stage 2, 53% at stage 3 and 44% at stage 4 (all p less than 0.02). This study demonstrates that improved efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia, is the basis of metformin's antihyperglycaemic action. PMID- 1759921 TI - A reliable screening test for coeliac disease: enzyme-linked immunosorbent assay to detect anti-gliadin antibodies in serum. AB - A simple, rapid, highly reproducible enzyme-linked immunosorbent assay detecting anti-gliadin antibodies in serum to screen for coeliac disease (CD) is described. By combining the results of anti-gliadin IgA and IgG determinations the overall sensitivity of the assay was found to be 100% and the specificity 96% for children and 99% for adults. Significantly elevated antigliadin IgA and IgG antibodies were detected in all 20 children and all 25 adults with untreated CD. False positive results were found in 1/79 histologically normal control and 5/86 disease control children, while for adults false positive rates were 0/74 and 1/34 for the healthy and disease control groups, respectively. Anti-gliadin IgA and IgG was measured in serum samples from 52 coeliac patients (11 children and 41 adults) treated with a gluten-free diet (GFD). Each of the children and 28 of the adults who followed a strict GFD had significantly lower IgA and IgG levels than untreated CD patients. The serum anti-gliadin IgA and IgG levels of the 13 adults not complying with a GFD were similar to those found for untreated CD patients. This assay is recommended as a screening test for CD as well as a tool for follow-up of treated patients. PMID- 1759922 TI - Acute Barmah Forest polyarthritis. AB - More than 60 arboviruses have been isolated in Australia with the human pathogenicity of the majority yet to be determined. Recent reports outline extensive clinical and sub-clinical infection occurring in Eastern Australia by such agents as Ross River and Barmah Forest viruses. We describe the clinical features of two patients with an acute polyarthritis associated with serological evidence of acute Barmah Forest virus infection to alert physicians to this form of viral polyarthritis and highlight the need to consider this agent when confronted with patients with an acute 'viral-type' polyarthritis in whom serology for Ross River virus is negative. PMID- 1759923 TI - Adult T-cell leukaemia lymphoma in an aborigine. AB - A 44-year-old Aborigine with Adult T-cell Leukaemia/Lymphoma (ATLL) due to HTLV-I is reported. He presented with transverse myelitis of subacute onset, and subsequently developed frank T-cell leukaemia complicated by splenomegaly and hypercalcaemia. Cell surface marker studies showed a phenotype of CD3+ CD4+ CD8- CD25+, and serological and molecular studies confirmed HTLV-I infection. This is the first report of ATLL in an Australian Aborigine. PMID- 1759924 TI - Fulminant metoclopramide induced neuroleptic malignant syndrome rapidly responsive to intravenous dantrolene. AB - We report a case of fulminant neuroleptic malignant syndrome in a man aged 70 developing within 12 hours of starting six-hourly intravenous metoclopramide. The muscle rigidity and hyperpyrexia were unresponsive to intravenous benztropine but resolved within one hour of intravenous dantrolene 2 mg/kg. Within six hours the patient had a partial relapse which resolved completely following further intravenous dantrolene 2 mg/kg. This case demonstrates that the rapid effect of intravenous dantrolene can be life saving in fulminant neuroleptic malignant syndrome. PMID- 1759925 TI - Multiple cardiac papillary fibroelastomas and rheumatic heart disease. AB - A case of severe rheumatic mitral stenosis was found to have multiple echodense masses attached to the ventricular surface of the mitral valve and papillary muscle at preoperative 2-dimensional echocardiography. Subsequent surgery involved mitral valve replacement and excision of the masses. Complete excision was confirmed by intraoperative transoesophageal echocardiography. Histologic examination of the surgical specimens showed typical papillary fibroelastomas. This is the first case report of multiple papillary fibroelastomas in association with rheumatic valvular disease demonstrated by 2-dimensional echocardiography. PMID- 1759926 TI - Invasive aspergillosis in AIDS. AB - Invasive aspergillosis (IA) is a rare infection in patients with the Acquired Immune Deficiency Syndrome (AIDS). We report the first Australian cases of histologically and microbiologically proven IA diagnosed antemortem in AIDS patients. We also describe the first case of laryngeal involvement and the unusual case of a pneumothorax due to IA. These three cases illustrate the varied clinical and pathological features of IA in AIDS and highlight some of the difficulties in diagnosis and treatment. The infections occurred in the setting of advanced immunodeficiency and multiple opportunistic infections and responded poorly to treatment. PMID- 1759927 TI - Giant cell arteritis in two Chinese patients. AB - Giant cell arteritis is virtually unknown in Orientals. We report two cases of histologically proven giant cell arteritis in two elderly Chinese men, one of whom presented with typical symptoms and the other with occult features of the disease. PMID- 1759928 TI - A randomised blinded study in colonic lavage for colonoscopy. PMID- 1759929 TI - Cerebral venous thrombosis associated with antithrombin III deficiency. PMID- 1759930 TI - The Arthur E. Mills Oration. Self-regulation and the professions: continuing legal education and regulating the regulators. PMID- 1759931 TI - An unusual case of chronic cough. PMID- 1759932 TI - 'Medical informatics'--a bridge between the clinician and the computer scientist. PMID- 1759933 TI - More complications of coeliac plexus blockade. PMID- 1759934 TI - One swallow doth not summer make. PMID- 1759935 TI - Cyclosporin A and mefenamic acid in a renal transplant patient. PMID- 1759936 TI - Septal lesions lower responding under fixed-ratio schedules of reinforcement. AB - Albino Sprague-Dawley rats with complete septal lesions and rats with control operations were studied under fixed-ratio (FR) schedules of reinforcement. Both groups were trained for 10 sessions each under FR 10, 20, 40, 60, 80, and 100. In contrast to findings from progressive FR studies and some simple FR studies, septal lesions resulted in lower overall and local response rates along with longer postreinforcement pauses. These effects were especially evident during the FR 100 schedule of reinforcement. A comparison of reinforcement rate as a function of FR size within the context of behavioral economics (i.e., a demand function) indicated that septal lesions did not alter the reward value of food. These findings suggest that responding on FR schedules of reinforcement can be altered by the various procedures used to train rats to reach the terminal value of a reinforcement schedule. PMID- 1759937 TI - Selectivity in paternal and infanticidal responses by male mice: effects of relatedness, location, and previous sexual partners. AB - Male mice tend to be infanticidal to unrelated infants but parental to their own offspring. The present study examines three hypotheses that might explain this apparent discrimination. There was no evidence of selective infanticide toward infants encountered for the first time on the basis of kinship, location, or cues associated with previous sexual partners. However, males tended to direct more paternal responses toward their own unfamiliar infants than toward unrelated infants, infants encountered in the male's home cage than those in the cage of another male, and when cues associated with a previous sexual partner were present. Data suggested that the responses of females to male intruders might influence the responses of those males. It was concluded that the infanticidal responses of male mice are mediated by a particular state of the male but that males in a noninfanticidal state may vary their paternal responsiveness on the basis of direct and indirect cues concerning relatedness. PMID- 1759938 TI - Sequencing of behaviors in Aplysia fasciata: integration of feeding, reproduction, and locomotion. AB - To begin studying the neural basis of higher-order decision-making in Aplysia fasciata, we examined individual bouts of behavior in various conditions of access to food and/or mates. We then determined rules governing transitions between bouts. The data indicate that a single intermediate condition, moving in place, may be centrally related to transitions between behaviors. In all conditions, over 85% of all transitions between behaviors were via moving in place. Moving in place tended to precede and follow other categories of activity (crawling, swimming, immobile), and feeding. Also, moving in place apparently represents a fixed proportion of all bouts of behavior. In each condition, moving in place represented approximately 40% of all bouts, while the number of bouts of other behaviors varied markedly. After a bout of moving in place there was a strong tendency for the animal to return to the behavior performed before moving in place. Additional preferred sequences of behavior were also seen. Courtship tended to precede mating, and crawling preceded swimming. PMID- 1759939 TI - Sensitization of amphetamine-stereotypy reduces plasma corticosterone: implications for stereotypy as a coping response. AB - The potential coping functions of amphetamine-induced stereotypy were investigated using a physiological index of stress or arousal, plasma corticosterone level. A series of five injections of d-amphetamine was used to enhance stereotyped behavior in control animals as well as in rats with bilateral dopamine-depleting lesions of the caudate-putamen. This regimen of amphetamine injections significantly increased stereotyped behavior and also reduced the normal elevation in corticosterone produced by treatment with d-amphetamine. This effect was apparent in both control and lesioned animals. These results support the hypothesis that amphetamine-induced stereotyped behavior functions to reduce stress or arousal and additionally suggest that this effect is largely independent of underlying dopaminergic mechanisms. PMID- 1759940 TI - The enhancement of retention induced by vasopressin in mice may be mediated by an activation of central nicotinic cholinergic mechanisms. AB - Immediate post-training subcutaneous administration of lysine vasopressin (LVP, 0.003-1.00 microgram/kg) enhanced retention, whereas the vasopressin antagonist AAVP (0.01-0.30 microgram/kg) impaired it, in male Swiss mice tested 48 h after training in an inhibitory avoidance task. Both effects were dose-dependent. Neither LVP nor AAVP affected response latencies in mice not given the footshock on the training trial. The simultaneous administration of AAVP at a dose (0.01 microgram/kg) which had no effect on retention shifted the dose-response curve of LVP to the right. Nicotine (1.0-30.0 micrograms/kg, sc), a central nicotinic cholinergic agonist, also facilitated retention in a dose-related manner without affecting the retention performance of unshocked mice. The effect of nicotine was prevented by the central acting nicotinic cholinergic receptor antagonist mecamylamine (5 mg/kg, sc.). In contrast, neither hexamethonium (5 mg/kg, sc), a peripheral acting nicotinic receptor blocker, nor atropine (0.5 mg/kg, sc) or methylatropine (0.5 mg/kg, sc), two anticholinergic drugs which are known to act on muscarinic cholinergic receptors, prevented the effect of post-training nicotine. The effects of LVP and nicotine were time-dependent, suggesting that both treatments enhanced retention by influencing post-training processes involved in memory storage. Low doses of nicotine (1.50 microgram/kg, sc) or the central anticholinesterase physostigmine (35 micrograms/kg, sc) and LVP (0.003 microgram/kg, sc), which had no effect on retention when administered alone, produced a synergistic interaction when given together following training. The influence of LVP (0.03 microgram/kg, sc) on retention was prevented not only by AAVP (0.01 microgram/kg, sc) but also by mecamylamine (5 mg/kg, sc), whereas the effects of nicotine (10.0 micrograms/kg, sc) were prevented only by mecamylamine. These results suggest that the enhancement of retention induced by vasopressin is probably due to an activation of central nicotinic cholinergic mechanisms which are critical for memory formation. PMID- 1759941 TI - Dose- and delay-dependent working/episodic memory impairments following intraventricular administration of ethylcholine aziridinium ion (AF64A). AB - The present study examined the effects of intraventricular administration of the cholinergic neurotoxin ethylcholine aziridinium ion (AF64A) on performance of a radial arm maze task. Male Sprague-Dawley rats were trained to perform a delayed nonmatch to sample radial arm maze task in which a 1-h delay was imposed between the fourth and fifth arm selections. Following acquisition, animals were injected bilaterally with AF64A (1.5 or 0.75 nmol/side) or artificial cerebrospinal fluid into the lateral cerebral ventricles and allowed 7 days to recover before behavioral testing resumed. Significant dose- and delay-dependent impairments in the radial maze performance were observed in AF64A-treated rats as evidenced by fewer correct choices following the delay and by more errors to complete the task. Long-term testing in this task revealed significant recovery of memory performance. These findings indicate dose-dependent impairments in memory following intraventricular administration of AF64A and spontaneous behavioral recovery following such insult. PMID- 1759942 TI - Increased generalization between drug-related interoceptive stimuli with delayed testing. AB - Although the flattening of generalization gradients over time has been widely investigated using exteroceptive stimuli, little attention has been given to generalization involving interoceptive stimuli. To investigate generalization between internal states, Sprague-Dawley rats were given either 0.835 ml/kg chloropent or 15 mg/kg sodium pentobarbital. Both drugs produced asymmetrical state-dependent retention of a passive avoidance response, that is, good retention in the "same state" conditions (i.e., the drug-drug and no drug-no drug conditions) as well as in the no drug-drug conditions but poor retention in the drug-no drug conditions, at both 1- and 7-day retention intervals. Furthermore, subjects trained in one drug state (pentobarbital or chloropent) demonstrated disrupted performance when tested 1 day later in another drug state, but good performance when tested 7 days later in the other drug state, indicating a decrement in the discriminability of the two drug states after 7 days. This outcome demonstrates that generalization gradients between drug states flatten over time. Moreover, these results suggest that memory for attributes of internal stimuli undergoes changes similar to those found for exteroceptive stimuli. Implications for contextual cues models of forgetting are considered. PMID- 1759943 TI - Selective fimbria and thalamic lesions differentially impair forms of working memory in rats. AB - Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes. PMID- 1759944 TI - Altered daylength affects dendritic structure in a song-related brain region in red-winged blackbirds. AB - Substantial neural and behavioral plasticity occurs in the avian song system in adulthood. Changes in the volume of one of the song control nuclei, robustus archistriatalis (RA), have been associated with seasonal changes in singing behavior in adult canaries (Serinus canarius) and red-winged blackbirds (Agelaius phoeniceus). The present work assessed the effects of changed daylength on dendritic morphology in RA in adult male red-winged blackbirds. Brains from hand reared red-winged blackbirds maintained on long days or long days followed by short days were stained with a Golgi-Cox procedure. Dendritic morphology and spine density of type IV neurons from nucleus RA were compared between long and short day birds. Neurons from short day birds have smaller dendritic fields than neurons from long day birds, with the difference greatest for distal dendrites. In addition, the density of dendritic spines is significantly smaller for neurons from short day birds. Together, these changes result in the loss of approximately 40% of the spines on this neuron class. In previous work in adult female canaries, external testosterone administration has been shown to be associated with increases in dendritic field size and synapse number. The similarity of the neuronal changes in RA that are associated with the two sorts of manipulations suggest that some consequences of altered daylength are mediated by changes in the levels of gonadal steroids. PMID- 1759945 TI - Common regulation of feeding and mating in Aplysia fasciata: pheromones released by mating and by egg cordons increase feeding behavior. AB - We examined whether pheromones released by reproductive behaviors (mating and egg laying) affect feeding behavior. A preliminary experiment demonstrated that the quantity of food eaten can be used to measure the effects of pheromones on feeding. Using this measure, we then showed that Aplysia that were prevented from mating, but that were in the same aquarium as mating conspecifics, eat more food than do Aplysia in a medium lacking mating animals. Mating and feeding were not temporally correlated, indicating that pheromones released by mating probably do not initiate feeding, but rather modulate feeding after it has begun. Aplysia that were in the same aquarium as freshly deposited egg cordons also ate more than did animals in a medium lacking eggs. PMID- 1759946 TI - Adult blood pressure reduction in spontaneously hypertensive rats reared by normotensive Sprague-Dawley mothers. AB - Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) normotensive, and Sprague Dawley (SD) normotensive rats were either reared by their natural mothers (controls) or fostered to a mother of one of the other strains. The effects of rearing environment were assessed by measures of body weight at weaning and adult resting mean arterial blood pressure (MAP) and heart rate (HR). At weaning, SHR control rats weighed less than WKY controls which in turn weighed less than SD controls. SHR and WKY rats reared by SD mothers weighed significantly more than their respective controls, whereas SD rats reared by either SHR or WKY mothers weighed less than SD control rats. Manipulation of the maternal environment was attended by a change in adult resting MAP in only one group. SHR rats reared by SD mothers had MAPs which were significantly lower than SHRs reared by their natural mothers. No within-strain adult HR differences were observed between control and cross-fostered groups. These data indicate that the effects of cross fostering on adult resting MAP previously reported for SHR and WKY animals are generalizable to another normotensive strain. That is, genetically hypertensive (SHR) animals exposed to a normotensive (WKY or SD) maternal environment display a reduction in adult resting MAP, whereas hypertension or an increase in adult MAP is not induced in normotensive rats (WKY or SD) as a consequence of exposure to a hypertensive maternal environment. PMID- 1759947 TI - Glucose effects on mecamylamine-induced memory deficits and decreases in locomotor activity in mice. AB - Peripheral glucose administration attenuates the effects of muscarinic cholinergic antagonists on several measures, including spontaneous alternation, inhibitory avoidance, and locomotor activity. The present study examined glucose interactions with mecamylamine, a nicotinic cholinergic antagonist, on these measures. Mecamylamine (5 mg/kg, sc) significantly impaired spontaneous alternation performance. Glucose (100 mg/kg, ip) administered with mecamylamine attenuated the impairment. Treatment with hexamethonium (5 and 10 mg/kg, sc), a peripheral nicotinic blocker, did not impair performance. Pretraining treatment with mecamylamine, but not hexamethonium, significantly reduced later retention latencies on inhibitory avoidance tests. Glucose, administered with mecamylamine prior to training, significantly attenuated the impaired test performance. Mecamylamine, but not hexamethonium, significantly decreased locomotor activity. In contrast to the attenuating effects of glucose on the other measures above, glucose administered with mecamylamine potentiated the decreased locomotor activity. These findings demonstrate that glucose influences the behavioral effects of a nicotinic cholinergic antagonist in a manner generally similar to that of muscarinic cholinergic antagonists, and supports previous evidence that circulating glucose interacts with central cholinergic functions. PMID- 1759948 TI - Scratching as a behavioral index of anxiety in macaque mothers. AB - The aim of this study was to assess the validity of the notion that anxiety influences maternal style in monkeys. To this end, we investigated the correlations between measures of the quality of mother-infant relationship and scratching, a behavior pattern that reflects a state of anxiety. The subjects were seven group-living macaque mothers and their infants observed during the first 12 weeks postpartum. Postpartum scratching by the mothers was positively correlated with both maternal possessiveness and maternal warmth, two composite measures of the quality of mother-infant relationship that reflect a possessive and attentive maternal style. Evaluation of the correlations between maternal rank and scratching before and after parturition indicated that interactions with their infants, not those with other group companions, were the main source of anxiety for the mothers. These results support the notion that anxiety influences maternal style in monkeys and suggest that studies aimed at investigating physiological and social correlates of maternal emotionality in nonhuman primates could use scratching as a useful and simple behavioral measure. PMID- 1759949 TI - Effects of systemic glucose injection on the development of amygdala kindling in rats. AB - The effects of systemic glucose administration on the development of electric amygdaloid kindling seizures were examined in Wistar rats. Daily intraperitoneal injections of glucose 100 mg/kg, 20 min prior to each amygdaloid stimulation did affect the rate of kindling development in comparison with the saline-injected group. The number of stimulations required to reach stage 5 was lower in animals treated with glucose. The facilitation of kindling development found in glucose treated rats is related to a specific decrease in the number of stimulations needed to evolve from stage 2 to stage 3. These results indicate that systemic glucose administration facilitates amygdaloid kindling in rats. PMID- 1759950 TI - The effect of flumazenil on acquisition, retention, and retrieval of spatial information. AB - The effect of flumazenil, a benzodiazepine-receptor antagonist, was evaluated in a spatial-reference memory procedure in a water maze. Flumazenil (1.0, 3.0, and 10.0 mg/kg, ip) did not modify acquisition of spatial information. Retention was similar between control and experimental rats 24 h after the training phase, as all groups showed bias to the target quadrant in a free swim trial. However, 10 days later, only flumazenil-injected rats (3.0 mg/kg) showed bias to the target quadrant. Flumazenil did not affect retrieval of spatial information in a group of well-trained rats. These results suggest that a benzodiazepine-receptor mediated endogenous mechanism is activated during learning of spatial tasks and that its blockade facilitates retention of spatial information. PMID- 1759951 TI - The factorial structure of sleep dissatisfaction. AB - Research into sleep problems has been dominated by a number of theoretical perspectives from each of which useful treatment applications have been derived. However, the rich diversity of problems that are subsumed under insomnia or sleep disturbance often remain unappreciated. This paper reports the results of a factor analysis performed on the combined items of two questionnaires designed to assess sleep disturbance. Six factors are described, two of which relate to cognitive aspects of sleep disturbance; two which map onto sleep onset and sleep maintenance problems; and two which are drawn from dissatisfaction with poor sleep. Correlations of factor scores with measures of neuroticism, worry and various sleep history variables provide a strong level of construct validity. The results are discussed in terms of their treatment implications. PMID- 1759952 TI - Time series analysis of obsessional behavior and mood during self-imposed delay and response prevention. AB - Time series analysis of more than a year of daily self-report of three subjects showed that self-imposed delay and response prevention was effective in decreasing obsessions and compulsions. The subject-controlled treatment had a varied effect on mood-anxiety decreased in two subjects, but depression increased in one. (A similar worsening of mood after elimination of obsessional behavior was found in a previous case study.) Apparently, successful treatment of obsessional behavior will not necessarily lead to an improvement in mood. Concurrent mood symptoms need to be targeted separately; and, plans should be made to deal with mood symptoms that may occur once obsessional behavior is removed. PMID- 1759953 TI - Responses to novelty in phobic and non-phobic cynomolgus monkeys: the role of subject characteristics and object features. AB - In two previous studies it has been shown that most surrogate-reared cynomolgus monkeys became phobic of a harmless object (a big paper bag) while most mother reared monkeys approached that object. Results of the first study seemed to indicate that the phobic reaction was restricted to the bag. Barnett and Cowan (Interdisciplinary Science Review, 1, 43-62, 1976) and Suomi (Anxiety disorder in childhood, pp. 1-23, 1986), however, reported that subjects (respectively rats and monkeys) that avoided a first novel object also avoided subsequent novel objects. In the present study we exposed phobic (bag-avoiding) and non-phobic (bag-approaching) monkeys from the study by Roder, Timmermans and Vossen (Behaviour Research and Therapy, 27, 221-231, 1989) to several big and small novel objects. Our results show that, irrespective of their rearing conditions, subjects that were phobic also avoided big novel objects while subjects that were non-phobic approached big novel objects. The reaction to small novel objects was independent of the previous reaction to the bag. PMID- 1759954 TI - Cognitive bias in symptomatic and recovered agoraphobics. AB - Symptomatic agoraphobics, recovered agoraphobics, and normal control subjects completed a series of sentence stems that had either ambiguous or unambiguous meanings, and had either a potentially threatening or a nonthreatening connotation. The written completions made by subjects to these stems were classified as indicating either a biased (i.e. threat-related) or unbiased interpretation of the meaning of the stem, and if a biased interpretation was made, whether the subject indicated efforts at adaptive coping with the perceived threat. Results indicated that symptomatic agoraphobics exhibited strong biases for interpreting information as threatening, relative to normal control subjects. Moreover, recovered agoraphobics resembled symptomatic agoraphobics more than normal control subjects, thus indicating that cognitive biases may persist following cessation of panic attacks and reductions in avoidance behavior. However, recovered agoraphobics also exhibited tendencies to cope adaptively with perceived threats whereas symptomatic agoraphobics did not. PMID- 1759955 TI - The effects of incorrect pain expectations on acquired fear and pain responses. AB - Previous experimental research on the effects of incorrect intensity expectations of aversive events can be criticized because intensity expectations were not manipulated independently from changes in objective intensity. The present study aims at investigating the effects of incorrect intensity expectations on the immediate and later responses to a painful stimulus, and on the acquisition of anticipatory responses, with proper experimental control. Subjects (n = 62) received 20 painful stimuli of varying intensity. In the control group intensities were correctly signalled on all trials by an analogue signal. On 3 trials the signal was too large in the overprediction condition, and too small in the underestimation condition. Underpredicted painful experiences were related to subsequent higher pain responses on the physiological level, but not on the subjective level; and to increased anticipatory responses (increased pain expectations, uncertainty, subjective fear, skin conductance responses). Skin conductance level also indicated increased fear after underpredicted experiences. Overpredicted painful experiences were related to a faster decrease in subjective fear compared to the control group, but did not influence other variables. The findings support the notion that underpredictions contribute to the acquisition of fear and disrupt habituation processes. The asymmetrical processing of the two kinds of incorrectly predicted experiences is discussed. PMID- 1759956 TI - Cognitive-behavioral treatment with and without response prevention for bulimia. AB - We compared cognitive-behavior therapy (CBT) with and without exposure and response prevention (ERP) in the treatment of eating disorder patients who both binged and purged, and reported abnormal attitudes concerning body weight and shape. Both treatments produced significant and comparable reductions in binge eating and purging, eating patterns, and attitudes about weight and shape at posttreatment. Treatment effects were generalized to improvements in different measures of general psychopathology, and were maintained over follow-ups of 3 and 12 months. The findings are consistent with prior research showing that CBT is an effective treatment for patients with the core features of bulimia nervosa. Furthermore, the data suggest that the addition of in-session exposure and response prevention does not enhance the effectiveness of the basic CBT program. PMID- 1759957 TI - Cognitive intrusions in a non-clinical population. I. Response style, subjective experience, and appraisal. AB - The present study identified distinctive response styles to unpleasant cognitive intrusions to further understanding of intrusive phenomena similar to those observed in obsessive-compulsive disorder and other anxiety disorders. Response styles were studied among 125 university students who completed a questionnaire describing and evaluating seven cognitive intrusions and inventories of depressive, anxious, and compulsive symptoms. Almost all subjects (99%) reported intrusions and 92% included effortful strategies in response to intrusions in their repertoire. Large differences were observed in the dominant strategy used. Three distinctive dominant response styles were identified including no effortful response (26%) and two effortful styles, attentive thinking (34%), and escape/avoidance (40%). The two groups using effortful strategies were more anxious and reported more difficulty removing intrusions. The group using escape/avoidance strategies reported more sadness, worry, guilt, and disapproval than subjects reporting no effortful response. The attentive thinking group reported more varied forms and more frequently triggered intrusions then the no effortful response group. Within subject analyses support the group comparisons and showed that intrusions eliciting escape/avoidance strategies were evaluated more disapprovingly than thoughts eliciting attentive thinking. The results are discussed in terms of Salkovskis' (Behavior Research and Therapy, 27, 677-682, 1985) formulation of obsessive-compulsive disorder and Borkovec's (Journal of Consulting and Clinical Psychology, 23, 481-482, 1985) and Barlow's (Anxiety and its disorders: The nature and treatment of anxiety and panic, 1988) discussions of worry and generalized anxiety. PMID- 1759958 TI - Biased cognitive operations in anxiety: accessibility of information or assignment of processing priorities? AB - There is considerable evidence that anxiety is associated with a cognitive bias favouring the processing of threat-related information. Bower's (1981) network model attributes this bias to the enhanced availability of mood congruent information from memory. However, certain experimental tasks do not reveal such a bias, when this effect is strongly predicted by the model. We note that all tasks which have demonstrated such mood congruent processing effects in anxious subjects share the requirement that these subjects must assign priorities to simultaneously available, and differentially valenced, alternative processing options. This feature has been consistently lacking in those paradigms we have found insensitive to the influence of anxiety. It is therefore suggested that anxiety is associated with the assignment of high processing priorities to threat related options, rather than with the facilitated availability of threat-related information from memory. This proposal was experimentally tested using a lexical decision task, which is sensitive to the accessibility of information from memory, under conditions which either do or do not introduce the requirement to assign priorities to alternative processing options. The results indicate that the facilitated processing of threat related stimulus words, shown by generalised anxiety patients, does indeed appear to reflect a bias in the assignment of processing priorities, rather than the enhanced availability of this information from memory. PMID- 1759959 TI - The effects of voluntary hyperventilation on patients with chest pain without coronary artery disease. AB - The present investigation was designed to examine panic symptom experience in patients with chest pain of nonorganic etiology, using a hyperventilation provocation procedure. Given the recent focus on panic disorder in patients with nonorganic chest pain, we assessed three indices of physiological arousal, subjective anxiety, and endorsement of DSM-III-R panic symptomatology in response to 3 min of voluntary hyperventilation. Subjects included 23 patients with nonorganic chest pain (CP sample) and matched normal controls (NC sample). The results indicate that hyperventilation produced significant increases in skin conductance, heart rate, and upper trapezious EMG in both CP and NC samples. Despite equivalent levels of physiological arousal and subjective anxiety, the CP sample endorsed a greater number of DSM-III-R panic symptoms relative to the NC sample. Examination of post-hyperventilation symptoms indicated that a greater percentage of the CP sample reported palpitations, nausea, and chest pain when compared with normals. Comparison of CP patients with and without Panic Disorder revealed no significant differences on any measure. The results suggests that hyperventilation plays a role in symptom experience in patients with nonorganic chest pain, although anxiety does not appear central in moderating this effect. PMID- 1759960 TI - The contribution of music vs instructions in the Musical Mood Induction Procedure. AB - The relative contribution of the instructions and the music to the effects of the Musical Mood Induction Procedure (MMIP) were investigated. Using an experimental procedure which minimised covert experimenter bias, subjects performed under both elation and depression mood inductions in one of four conditions: music present or absent by mood change instructions present or absent, using a crossover design. Results indicated that instructions were both necessary and sufficient to produce change on mood sensitive measures. Mood change effects were reduced by controlling for the effect of subjects who responded so as not to 'louse-up' the experiment. The MMIP seems to be much less musical than the name implies. Further research is needed to determine which aspects of the instructions contribute most to the changes on mood sensitive measures. PMID- 1759961 TI - A standardized behavioral group treatment program for obsessive-compulsive disorder: preliminary outcomes. AB - This paper provides outcome data about the efficacy of a behavioral group therapy program for obsessive-compulsive disorder (OCD). Thirty-six patients completed a 7-week outpatient treatment program which provides: (1) education about OCD and its treatment, (2) instruction in a cognitive and behavioral approach to the self treatment of OCD and (3) guided behavioral treatment. Significant improvement in obsession, compulsion, and depression scores were observed at completion of the group and at 3 month follow-up. Significant improvement in obsessions and compulsions was observed for both patients taking anti-obsessional medications and those who did not. PMID- 1759962 TI - Inactivation of 15-lipoxygenases by acetylenic fatty acids. AB - The inactivation of soybean lipoxygenase-1 and of rabbit reticulocyte lipoxygenase by five selected acetylenic fatty acids was studied. In all cases the inactivation was time-consuming and depended on the concentration of the inactivator. The inactivation kinetics was measured and the data were fitted to a kinetic model based on the assumption of catalytic self-inactivation. The kinetic constants (Km-value and inactivation rate k2) calculated indicated that 7,10,13 eicosatrienoic acid was the most powerful inactivator for the soybean enzyme followed by 8,11,14-eicosatrienoic acid. The occurrence of an additional triple bond between C-4 and C-5 or between C-5 and C-6 strongly reduced the suicidal rate. With the reticulocyte enzyme, only small differences in the reactivities towards various acetylenic fatty acids have been observed. PMID- 1759963 TI - Intramitochondrial fatty acid activation enhances control strength of adenine nucleotide translocase. AB - In incubations with isolated rat liver mitochondria we studied the fuel properties of octanoate as medium-chain fatty acid and respiratory substrate and the extent of control exerted by adenine nucleotide translocase on mitochondrial respiration. While, compared with pyruvate, octanoate improved the hydrogen supply in the active state to be seen from a high reduction of the mitochondrial NAD(P) system and an increased delta psi, it also decreased the efficiency of energy transduction indicated by a low ADP/O ratio. Based on measurements of the dependence of respiration on the extramitochondrial ATP/ADP ratio, we conclude that a switch-over from pyruvate to fatty acid oxidation does not change the kinetic parameters which make respiration respond to the ATP/ADP ratio. It is shown that the decrease of the exchangeable intramitochondrial adenine nucleotide pool due to the activation of octanoate results in a decrease of the activity of the adenine nucleotide translocase and an increase of its flux control coefficient. PMID- 1759964 TI - Multiple forms of N-acetyl-beta-D-glucosaminidase of human urine: isolation, properties and the development of a practical approach of differentiation. AB - The two major tissue forms of N-acetyl-beta-D-glucosaminidase, A and B, and a minor form M were isolated from human urine by chromatography on DEAE-Trisacryl M and Con A-Sepharose. Forms A and B have a Km-value of about 0.75 mM for 4 nitrophenyl-beta-2-acetamido-2-deoxy-D-glucopyranoside, form M a corresponding value of 1.57 mM. The pH optimum was for all forms between pH 4.0 and 4.8. Forms A and M were heat labile, while form B was relatively heat stable. Using different binding properties of forms A and B on Trisacryl, a batch method was developed to differentiate both forms in human urine. This method can be easily performed and gives reproducible results. The intra-run and between-run precision for the separation of the two forms were below 10%. PMID- 1759965 TI - The influence of valinomycin induced membrane potential on erythrocyte shape. AB - In addition to previous observations indicating that membrane potential changes generated by various Donnan- and Nernst-potentials lead to erythrocyte shape transformations, we show in this paper that diffusion potential change, induced by valinomycin, governs erythrocyte shape transformations. In low KCl-medium valinomycin, transferring the positive Nernst-potential into a negative diffusion potential, transforms stomatocytes into echinocytes. Using modified erythrocytes with a reversed K/Na ratio, even positive diffusion potentials can be induced by valinomycin. In these cases, stomatocytes can be generated by valinomycin. It is shown that, additionally, valinomycin in large concentrations is itself stomatocytogenic, and that the fluorescent dye diS-C3-(5) also induces stomatocytes. This, however, is a side effect which does not contradict the potential dependence of shape transformation. Using non washed erythrocytes, resuspended in plasma, valinomycin, inducing negative diffusion potential, transforms most erythrocytes to echinocytes despite the stomatocytogenic effect of albumin. PMID- 1759966 TI - Effect of ethanol on epidermal growth factor receptor in buccal mucosa. AB - The effect of ethanol on buccal mucosal epidermal growth factor receptors was investigated. The buccal mucosal cells from adult rats were incubated in DMEM at 4 degrees C and 37 degrees C in the presence of various concentrations (0-5%) of ethanol and then assayed for EGF receptor binding using [125I]-EGF. The results of binding analysis showed that the cells incubated in the presence of ethanol displayed diminished [125I]-EGF binding. The receptor binding capacity was dependent upon ethanol concentration and was more pronounced at 4 degrees C. A 30% decrease in receptor binding occurred with 1% ethanol, 34% with 2.5% ethanol, while 5% ethanol caused a 42% decrease in binding. Scatchard analysis suggested that the decrease of [125I]-EGF binding to the buccal mucosal cells pre-incubated with ethanol was due to a decrease of the high affinity binding site (Bmax). The association constant of the high affinity EGF receptor remained unchanged. The results suggest that ethanol due to its untoward effect on the receptor binding of salivary GF interferes with the process of epithelial renewal, thus leading to weakening of the mucosal defense perimeter of soft oral tissue and the onset of dysplasia. PMID- 1759967 TI - Influence of urea on the glucose measurement by electrocatalytic sensor in the extracorporeal blood circulation of a sheep. AB - In an animal experiment with the electrocatalytic glucose sensor, measurements were carried out over one week in the extracorporeal circulation of a sheep. Glucose tolerance tests were performed, and the influence of increased urea concentrations in the blood on the glucose determination was investigated. The sensor constructed as a flow-through cell was integrated via a vascular graft outside the body into the carotid artery of the animal and activated by an external electronic unit of measurement. The glucose concentration was determined by measuring the impedance of the electrode/membrane system at various potentials. By means of a subsequent correlation analysis of the measured values obtained over one week, a calibration valid for the entire measurement period was established. After a zero adjustment, it was even possible to adopt the calibration from the glucose measurement of the preceding animal experiment. The investigations of the influence of urea on the glucose measurement showed that the error in measurement of the sensor, which is 20% on average, is only insignificantly increased when the urea level is raised beyond the maximum physiological concentration. PMID- 1759968 TI - Changes in the hemostatic system and compensatory responses during alimentary hyperlipidemia. AB - Compensatory responses tending to prevent a thrombotic state in rats fed a high lipid diet have been investigated. Platelet membranes from these animals had an increased cholesterol content but the membrane fluidity was found to be within values nearly normal. A decrease in phosphatidylethanolamine was noted. These changes may maintain normal platelet sensitivity to aggregating agents. In fact, platelets from hyperlipidemic rats were hypersensitive to thrombin, but not to adenosine diphosphate. In addition, platelets were apparently able to correct, at least in part, the stated hyperactivity of hyperlipidemic plasma to coagulate, as shown by thrombelastographic tests in both platelet-rich plasma and plasma from hyperlipidemic rats. Finally, thrombelastographic features of whole blood from these animals were found to be normal. This suggests an important role of blood cells in compensating plasma hyperactivity to coagulate during hyperlipidemia. PMID- 1759969 TI - [The postnatal development of EMG reactions of limb muscles to free fall stimulation. I. Studies in normal rabbits]. AB - The ontogenetic development of the vestibulospinal reaction following the free fall was studied in 11 rabbits ("Deutscher Riese") 8 to 20 days old by means of myographical recordings (EMG) synchronously derived from 3 muscles (M. triceps brachii caput lateralis, M. brachialis, M. quadriceps femoris vastus lateralis) by chronically implanted steel wire electrodes. With increasing age, rabbits show a sustained rise of EMG activity during fall and develop the ability to change the generated EMG activity under the condition of repeated stimulation. It is concluded, firstly, that more typical EMG reactions are produced with growing age, and secondly, that the ability to modify the intensity of the response to repeated free falls increases during postnatal development. PMID- 1759970 TI - [The postnatal development of EMG reactions of limb muscles to free fall stimulation. II. Studies of early postnatal hypoxic-burdoned rabbits]. AB - 12 rabbits ("Deutscher Riese") were exposed to a hypoxic atmosphere (FiO2 = 0.05) for 3 h at their 1st day of life. At the 7th or 13th day of life, steel wire electrodes were chronically implanted into 3 leg muscles in order to record the electromyograms (EMG). The myographic activity was derived during free fall (height of drop = 0.5 m) until the age of 20 days. The quantitatively analysed EMG data were compared with corresponding data of undisturbed growing control animals. Using various EMG parameters, a quantitative separation of hypoxic animals from the controls was successfully done by a discriminant analysis, the animals being 8 and 20 days of age, respectively. It can be concluded that 1. already a single perinatal hypoxic load influences the supraspinal motor system permanently at least up to the age of 20 days, and that 2. this supraspinal influence on the investigated vestibulospinal reaction changes with increasing age of the rabbits. PMID- 1759971 TI - Effects of salicylate on hepatocyte lactate metabolism. AB - We have examined the effects of salicylate on fluxes of lactate metabolism in rat hepatocytes using a steady state model. Salicylate produces an uncoupling effect, an inhibition of gluconeogenesis, a marked activation of pyruvate dehydrogenase flux, and an inhibition of endogenous fatty acid oxidation. Agents with known functions such as dinitrophenol and dichloroacetate were also compared in this system. The in vitro inhibition of gluconeogenesis caused by salicylate is not primarily related to the uncoupling effect. The fact that octanoate, but not palmitate, overcomes the salicylate inhibition of gluconeogenesis suggests that salicylyl CoA is involved in the inhibition. To relate in vitro studies to Reye's syndrome in vivo, in which medium chain dicarboxylic acids accumulate, we have also examined the effects of monomethyl suberate on liver lactate metabolism. This half ester is taken up by the hepatocytes, and causes inhibition of lactate gluconeogenesis, and uncoupling. Both salicylate and monomethyl suberate inhibit the oxidation of 0.2 mM octanoate by hepatocytes. PMID- 1759972 TI - Changes of brain gangliosides in the frontal cortex of rats chronically treated with amphetamine, clozapine, haloperidol and ethanol. AB - Rats were injected intraperitoneally daily for 20 days with amphetamine, haloperidol, clozapine and ethanol to investigate the participation of gangliosides in the reactivity of the brain to these drugs. All of these substances are able to modulate the ganglioside pattern of the frontal cortex. The major changes were observed after amphetamine and clozapine treatment. In both cases, GQ1b was significantly increased, whereas GM2 and GM3 were significantly diminished. Moreover, GD1a (after amphetamine) and GM1 (after clozapine) were decreased with respect to the controls. After haloperidol treatment both GQ1b and GT1b augmented, while after ethanol, only GM3 was increased. PMID- 1759973 TI - Thromboxane plasma level in kappa-carrageenin-induced acronecrosis of the tail in rats. AB - The thromboxane A2 (TXA2) plasma level in kappa-carrageenin (KC)-induced acronecrosis in the rat tail has been studied. TXB2 as stable metabolite of TXA2 was determined by a radioimmunoassay (RIA). 30 min after KC i.v. injection, the increase in the plasma TXB2 level was highest in Barby:Wistar rats but not in Halle:Wistar rats. Lambda-carrageenin (LC) increased the TXB2 levels in both strains of Wistar rats, although it did not induce acronecrosis. Drugs inhibiting TXB2 formation, namely dexamethasone, acetylsalicylic acid, Hoe 944, R 68070 or chlorpromazine, had only a small effect on acronecrosis frequency. Heparin inhibited TXB2 formation and acronecrosis frequency while the serotonin antagonist cyproheptadine decreased only the acronecrosis frequency but caused no change in TXB2 plasma level. These data demonstrate that the kappa-carrageenin induced acronecrosis is followed by an increased formation of TXA2 in rats. PMID- 1759974 TI - Mapping replication origins in yeast chromosomes. AB - The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms. PMID- 1759975 TI - Gene expression, cellular diversification and tumor progression to the metastatic phenotype. AB - Alterations in the expression of certain genes or in their products can render benign tumor cells metastatic. Experimentally this has been quickly performed by transferring dominantly acting oncogenes such as c-H-rasEJ into susceptible cells, but in vivo such a rapid qualitative change in a dominantly acting oncogene occurs only rarely, and progression to highly metastatic phenotypes is thought to occur through a slow stepwise process. Such slow changes can be reversible and need not involve known dominantly acting oncogenes, consistent with clinical observations. An important element of the natural progression of tumors to malignancy may be their ability to circumvent microenvironmental controls that regulate growth and cellular diversity and to evolve into heterogeneous phenotypes, a process that appears to involve mainly quantitative changes in gene expression but which can be rapidly stimulated in cell culture by the introduction of a dominantly acting oncogene. It is proposed that the highly malignant cells that have slowly evolved in vivo with only a few qualitative gene changes have undergone extensive cycles of diversification and accumulation of quantitative changes in the expression of genes that encode products that are related to malignancy and metastasis. Thus, highly malignant cellular phenotypes can arise quickly through specific qualitative changes in critical controlling genes or more slowly by less critical qualitative genetic changes, coupled with cellular diversification and accumulation of quantitative changes in gene expression. PMID- 1759976 TI - Discovery of the 9 + 2 subfibrillar structure of flagella/cilia. PMID- 1759977 TI - Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: I. Experimental design and exposure system. AB - The rationale for selection of an animal model, the experimental design, and the design and evaluation of an exposure system used in studies of 60-Hz magnetic fields are described. The studies were conceived to assay development of cancer and immune responsiveness in mice exposed to magnetic fields. The exposure system utilized a quadrupole-coil configuration to minimize stray magnetic fields. Four square-wound coil provided a uniform field within a volume occupied by 16 animal cages. The magnetic field had a mean flux density of 2 mT that varied less than +/- 10% within the volume occupied by animals' cages. The flux density decreased to less than 0.1 microT at a distance of 2 m from the coils. In each exposure system 32 animals could be housed in plastic cages. PMID- 1759978 TI - Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response. AB - This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0 tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups. PMID- 1759979 TI - Absence of a synergistic effect between moderate-power radio-frequency electromagnetic radiation and adriamycin on cell-cycle progression and sister chromatid exchange. AB - In our laboratories we are conducting investigations of potential interactions between radio-frequency electromagnetic radiation (RFR) and chemicals that are toxic by different mechanisms to mammalian cells. The RFR is being tested at frequencies in the microwave range and at different power levels. We report here on the 1) ability of simultaneous RFR exposures to alter the distribution of cells in first and second mitoses from that after treatment by adriamycin alone, and 2) on the ability of simultaneous RFR exposure to alter the extent of sister chromatid exchanges (SCEs) induced by adriamycin alone. This chemical was selected because of its reported mechanism of action and because it is of interest in the treatment of cancer. In our studies, Chinese hamster ovary (CHO) cells were exposed for 2 h simultaneously to adriamycin and pulsed RFR at a frequency of 2,450 MHz and a specific absorption rate of 33.8 W/Kg. The maximal temperature (in the tissue-culture medium) was 39.7 +/- 0.2 degrees C. The experiments were controlled for chemical and RFR exposures, as well as for temperature. Verified statistically, the data indicate that the RFR did not affect changes in cell progression caused by adriamycin, and the RFR did not change the number of SCEs that were induced by the adriamycin, which adriamycin is known to affect cells by damaging their membranes and DNA. PMID- 1759980 TI - Morphological and electrophysiological changes produced by electrical stimulation in cultured neuroblastoma cells. AB - Electric fields, which were equivalent to those generated by medical devices, were applied to cultured neuroblastoma cells (mouse and human) to test for morphological damage and to establish damage thresholds. Each of two methods of applying fields permitted flow of electrical current and minimized exposure of cells to electrode-breakdown products. One method consisted of a pair of parallel wires in a Petri dish by which current was delivered within a fixed volume of flowing tissue-culture media. With the other method, the cells were held in a confined geometrical chamber and current was applied via agar bridges. Under a given set of stimulation parameters, damage was found to be variable from cell to cell. By changing the strength of the electric field (frequency and duration of stimulation held constant), thresholds of several V/cm were found above which cell damage could be reliably produced. Depending on the intensity of the field, damage took the form of cell lysis or damage to neurites. Intracellular recordings from the mouse neuroblastoma cells revealed a correlation between a decline in resting transmembrane potential and stimulus intensity. Human neuroblastoma cells were less susceptible to damage than were the mouse neuroblastoma cells, given the same strength of applied electric fields. PMID- 1759981 TI - Modification of the 1979 "Denver wire code" for different wire or plumbing types. AB - This article examines "wire configuration coding" as used to estimate relative residential AC magnetic field exposure in epidemiological studies--and the need to alter such coding for time or locations other than those in which the code was developed. Effects of different secondary wire practices are particularly examined. PMID- 1759982 TI - Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response. AB - The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli. PMID- 1759983 TI - The PLAT Study: a multidisciplinary study of hemostatic function and conventional risk factors in vascular disease patients. AB - In this paper are reported the basal results of a multidisciplinary, multicenter study designed to explore in a population with ischemic disease the relation between hemostatic variables, conventional risk factors and atherothrombotic sequelae. 953 patients less than or equal to 69 yrs with documented coronary, cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months. Examinations included hemostatic and lipid laboratory assays, arterial Doppler examination, cerebral computerized tomography and nuclear magnetic resonance, exercise electrocardiogram and coronary angiography. Fibrinogen (301.4 +/- 71.52 mg/dl) correlated positively with antithrombin III (r = 0.27) and leukocytes (r = 0.25), negatively with HDL-cholesterol (r = 0.18) and tended to increase with smoking. Heavy smokers had higher leukocyte counts than non-smokers (8.0 +/- 2.0 vs. 7.2 +/- 2.1 x 10(3)/microliters), higher triglycerides (1.87 +/- 1.12 vs. 1.53 +/- 1.35 mmol/l) and lower HDL-cholesterol (0.93 +/- 0.27 vs. 1.00 +/- 0.25 mmol/l). FVII correlated positively with triglycerides (r = 0.16) and protein C (r = 0.45). vWF:Ag (145.4 +/- 70.58%) ad FVII:C (139.7 +/- 59.10%) were positively correlated (r = 0.44). FVIII:C correlated positively with fibrinogen (r = 0.21). Myocardial infarction survivors with associated cerebral and peripheral vascular lesions had higher FVIII:C, FVII, fibronogen and vWF:Ag. These findings suggest that hemostatic factors may enhance and/or mediate the effects of conventional risk factors in atherothrombotic ischemic events. PMID- 1759984 TI - Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. AB - The effect of fish oil ingestion (10 g MaxEPA/day) on the susceptibility of plasma lipoproteins to peroxidation was examined in 20 smokers (study A and B) and 22 nonsmokers (study C). The subjects were examined at the onset of each study (baseline values), divided into control and experimental groups and reexamined 4 weeks later. Smokers were examined 40 h after abstention from smoking (0 time) and 90 min after acute smoking (4-6 cigarettes). The parameters studied were TBARS, which provide an indication of peroxidative injury, and metabolism of conditioned LDL by macrophages as a biological indicator. These parameters were significantly higher (P less than 0.05-0.001) when the 90 min values of smokers were compared to time 0. After 4 weeks of fish oil ingestion, a significant rise above baseline values (33-50%) in plasma and LDL TBARS was found in smokers examined at time 0 and after acute smoking. Peroxidative modification of LDL isolated from smokers fed fish oil resulted in significantly higher TBARS (34-41%) and its metabolism by macrophages was higher (65-139%) compared to baseline values. In nonsmokers, the baseline values of the above parameters were lower than in smokers. Ingestion of fish oil resulted in a significant rise in TBARS in plasma (33%), LDL (137%), conditioned LDL (36-40%) and metabolism of conditioned LDL (70%) by macrophages. In 6 nonsmokers and 4 smokers, 400 mg of vitamin E/day were given with the fish oil. In the nonsmokers, vitamin E counteracted the effect of fish oil more effectively than in the smokers. In the light of the present results, indiscriminate recommendation of fish oil supplementation to the population at large should be cautioned. PMID- 1759985 TI - Effect of clentiazem on lipid profile, lipoprotein composition and aortic fatty streaks in cholesterol-fed rabbits. AB - Numerous experimental studies have reported that common antihypertensive drugs such as diuretics, beta-blockers, and methyldopa have adverse effects on plasma lipids and lipoproteins. The present study was designed to define the effect of clentiazem (10 mg/kg/day) an antihypertensive drug, on hyperlipidemia in rabbits on a cholesterol-rich diet (1%) for 12 weeks. Compared with controls, clentiazem treated rabbits had lower plasma concentrations of triglycerides (55%), total cholesterol (24%), free cholesterol (27%), esterified cholesterol (23%) and phospholipids (24%). The decrease in cholesterol was accounted for by a reduction of VLDL-cholesterol (13%), IDL-cholesterol (24%) and primarily LDL-cholesterol (45%). Neither HDL-cholesterol nor chemical composition of VLDL, IDL, LDL and HDL was altered. When the aortic atherosclerotic involvement was evaluated by computerized planimetry, a 24% reduction of lesions was noted in clentiazem treated animals (P less than 0.05). Similarly, cholesterol content extracted from aortic wall was decreased. Our data therefore demonstrated that clentiazem is a potential antiatherosclerotic agent capable of decreasing plasma lipids and atherogenic lipoproteins as well as aortic fatty streaks. PMID- 1759986 TI - Different locations of cholesteryl ester transfer protein and phospholipid transfer protein activities in plasma. AB - Activities of cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) were measured in plasma of four vertebrate species: man, rabbit, pig, and rat. The activities were measured in the absence and presence of antibodies raised against purified human CETP. PLTP activities were present in all four species with highest values in pig (11.7 +/- 1.2 U/ml) and human plasma (9.2 +/- 1.6 U/ml). Considerable lower activities were found in rabbit (3.5 +/- 0.6 U/ml) and rat plasma (1.6 +/- 0.7 U/ml). These activities were not affected significantly by antibody against human CETP. CETP activities could be measured in human (0.23 +/- 0.05 U/ml) and in rabbit plasma (0.19 +/- 0.03 U/ml). CETP activity in human plasma was inhibited over 97% by antibody against human CETP. Plasma was chromatographed on a Superose 6 gel filtration column. Average HDL particle sizes in the four species differed notably and decreased in the order: rat HDL greater than rabbit HDL greater than human HDL greater than pig HDL. A separation of the two lipid transfer activities was evident after gel filtration chromatography. The peak of the PLTP activity coeluted with a fraction of HDL particles with the size of human HDL2 (particle weights 300-375 kDa). CETP activity in human and rabbit plasma coeluted largely with relatively small HDL particles (particle weights 140-180 kDa). These results show that CETP and PLTP activities are located in different macromolecular complexes. PMID- 1759987 TI - Human monocyte characteristics are altered in hypercholesterolaemia. AB - Peripheral blood monocytes are involved during atherogenesis in adhering to endothelium, migrating into the subendothelial space and taking-up lipoproteins to become macrophage/foam cells. We have assessed whether peripheral blood monocyte characteristics are altered in human hyperlipidaemia in age/sex/smoking status matched pairs of patients and controls. Monocytes from the hypercholesterolaemic patients, as opposed to the controls, were more sensitive to stimulation by the agonist, N-formyl-methionyl-leucyl-phenylalanine, with respect to chemokinesis (stimulation index 1.48 +/- 0.17 vs. 1.10 +/- 0.14), chemotaxis (4.05 +/- 0.55 vs. 2.72 +/- 0.24) and adhesion to porcine aortic endothelial monolayers (1.26 +/- 0.05 vs. 1.17 +/- 0.06). The patients' monocyte total surface expression of the adhesion glycoprotein CD11b/CD18 (37.5 +/- 7.1 vs. 36.0 +/- 7.1), but not CD11c/CD18 (31.6 +/- 7.2 vs. 31.4 +/- 6.8), was increased; however, the monocytes in hyperlipidaemia were larger (9.15 +/- 0.11 microns vs. 8.98 +/- 0.11 microns) such that the surface density of CD11b/CD18 was not altered (0.144 +/- 0.029 vs. 0.142 +/- 0.029). The data suggest that circulating monocytes are functionally different in hypercholesterolaemia. This may explain the increased involvement by monocytes in hypercholesterolaemia related atherogenesis. PMID- 1759988 TI - Effects of sympathetic nerves on collateral vessels in the limb of atherosclerotic primates. AB - This study was performed to examine effects of sympathetic nerves on collateral vessels in the limb. We studied normal (N) and atherosclerotic (AS) cynomolgus monkeys that were fed atherogenic diet for 21 months. A common iliac artery was ligated 13 months before hemodynamic measurements. Using histofluorescence microscopy, a plexus of noradrenergic nerves was identified in the adventitia of collateral vessels. We measured blood flow to the limb with microspheres, and the pressure gradient from aorta to the iliac artery beyond the occlusion. The lumbar sympathetic chain was stimulated electrically at 3 Hz (SNS-3) and 15 Hz (SNS-15). In normal monkeys, conductance of collateral vessels (in ml/min per 100 g per 100 mm Hg) was 19 +/- 3.6 (mean +/- SE) during control, 14 +/- 1.6 during SNS-3, and 9.8 +/- 0.9 during SNS-15 (P less than 0.05 vs control). In AS monkeys, collateral conductance was 12 +/- 2.9 during control, 7.5 +/- 1.7 during SNS-3 and 3.9 +/- 1.8 during SNS-15 (P less than 0.05). In summary, collateral vessels in the limb are innervated and sympathetic stimulation produces pronounced constriction of collateral vessels in both normal and atherosclerotic monkeys. Thus, the effectiveness of collateral vessels in maintaining blood flow to the limb may be compromised by increased activity of sympathetic nerves. PMID- 1759989 TI - Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency. AB - Six homozygous, 10 heterozygous and 8 unaffected subjects in a CETP deficient family confirmed by CETP gene analysis were studied to characterize serum lipoproteins separated by ultracentrifugation, and to examine the relations between CETP levels and lipoprotein lipid concentration and composition. The serum CETP levels were measured by radioimmunoassay using 125I-labeled monoclonal antibodies (TP2). The serum CETP levels in the homozygotes were undetectable and those in the heterozygotes were significantly lower than those in the unaffected subjects (1.5 +/- 0.1 vs. 2.2 +/- 0.5 microgram/ml, P less than 0.01). In the HDL fraction, esterified cholesterol (EC) levels in the homozygotes were significantly increased (P less than 0.01), and those in the heterozygotes were slightly increased (n.s.), in comparison with those in the unaffected and the normolipidemic controls. The EC levels in the IDL fractions were lower in the homozygotes than in the normolipidemic controls. The EC/triglyceride (TG) molar ratios in IDL, the fraction obtained from the homo- and heterozygotes, were lower than those from the unaffected subjects (P less than 0.01 and less than 0.01, respectively), and the EC/TG ratios in the HDL fraction obtained from the homo- and heterozygotes were higher than those from the unaffected subjects (P less than 0.01 and n.s., respectively). Linear regression analysis showed that positive correlates of the serum CETP levels in all subjects were: IDL-EC (r = 0.463), HDL-TG (r = 0.603) and VLDL- and IDL-EC/TG ratio (r = 0.698 and 0.843).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1759990 TI - A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper. AB - Oxidation of low density lipoprotein (LDL) leads to more rapid uptake by arterial wall macrophages and foam cell formation. Inhibiting LDL oxidation may impede these processes and offers a new mechanism to retard atherogenesis. The 21 aminosteroids, derived from methylprednisolone, are potent inhibitors of free radical production by stimulated monocytes and also are scavengers of lipid peroxyl radicals. The 21-aminosteroid, U74500A, was added to a mixture of low density lipoprotein cholesterol and human monocytes to which lipopolysaccharide was add to stimulate the monocytes. At a final concentration of 10 microM, U74500A reduced the production of lipid peroxidation from 6.10 +/- 1.11 to 0.84 +/- 0.16 nmol (mean +/- SEM) MDA equivalent/1 x 10(6) monocytes, as measured by a thiobarbituric acid reacting substance (TBARS) assay. Similarly 10 microns U74500A reduced Cu2+ induced LDL oxidation from 12.28 +/- 0.10 (in vehicle) to 0.49 +/- 0.12. These observations suggest that the 21-aminosteroids should be evaluated in animal models as a potential therapy to retard atherogenesis, especially considering their apparent lack of mineralocorticoid and glucocorticoid side-effects. PMID- 1759991 TI - Chemotaxis of the monocyte cell line U937: dependence on cholesterol and early mevalonate pathway products. AB - In the present study we investigated the influence of cholesterol depletion and hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibition on chemotaxis of the human monocytic cell line U937. Chemotaxis was nearly completely depressed after incubation for 24 h in the absence of lipoproteins. This was accompanied by a significant decrease in cellular cholesterol. Addition of 10 micrograms/ml low density lipoprotein (LDL) for 2 h to the cholesterol depleted cells restored chemotaxis. Free cholesterol had no effect under these conditions. Inhibition of HMG-CoA reductase by pravastatin (0.01-1.0 mM) for 20 or 72 h also reduced chemotaxis. However, this effect was not accompanied by a decrease in cellular cholesterol when cells were grown in the presence of lipoproteins. The effect of pravastatin could be reversed by the addition of mevalonate. Addition of LDL did not change the response to pravastatin. We propose that the availability of cholesterol plays an important role in cellular chemotaxis. Furthermore, it can be suggested that other products of the mevalonate pathway apart from cholesterol may contribute to the regulation of chemotaxis. PMID- 1759992 TI - Pathology of atherosclerosis in cholesterol-fed, susceptible mice. AB - In recent years the C57BL/6J mouse has gained popularity as a model for studying the genetics of diet-induced atherosclerosis. After 10-20 weeks of consuming a diet enriched with saturated fat and cholesterol, it develops fatty streak-like lesions in the valve sinus region of the ascending aorta. The current study shows that continuing the atherogenic diet for a further 15 weeks leads to the development of fibro-fatty lesions which have many of the characteristics of human atheromatous plaques. This finding lends credence to the use of C57BL/6J mice for studying the pathogenesis of atherosclerosis. PMID- 1759993 TI - Isolated muscular sarcoidosis causing fever of unknown origin: the value of gallium-67 imaging. AB - An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 (67Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using 67Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis. PMID- 1759994 TI - A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large bowel cancer. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis and tumor growth in the rodent colon. We assessed NSAID use in relation to risk of human large-bowel cancer in a hospital-based, case-control study of 1326 patients with colorectal cancer and 4891 control patients. For regular NSAID use that continued into the year before interview, the multivariate relative risk estimate was 0.5 (95% confidence interval, 0.4 to 0.8); the estimate decreased as the duration of use increased, but the trend was not statistically significant. Similar results were obtained whether cancer or non-cancer controls were used, and the inverse association was apparent for both colon cancer and rectal cancer in men and women and in subjects younger and older than 60 years. Regular NSAID use that had been discontinued at least 1 year previously and non-regular use were not associated with risk. Almost all regular NSAID use was of aspirin containing drugs. The present data suggest that the sustained use of NSAIDs reduces the incidence of human large-bowel cancer. PMID- 1759995 TI - Travel in eastern Europe. Guidelines for patients. AB - Some patients need medical preparation and physician counseling before traveling to eastern European countries. In addition to baseline immunizations, a measles booster, a polio booster, typhoid vaccination, and immune globulin prophylaxis against hepatitis A may be indicated. Advice should also be given regarding air pollution, contaminated food and water, civil unrest, motor vehicle mishaps, and each country's policy on HIV screening. Because the level of healthcare may be poor, contact with American or British embassies or consulates is recommended in an emergency. PMID- 1759996 TI - A review of child psychotherapy research since 1963. AB - Reports on individual nonbehavioral child and adolescent psychotherapy since 1963 are reviewed. Inclusion criteria required some minimal contrasting group. Forty three studies were assessed for basic methodological adequacy and main findings. The authors conclude that summary impressions from this body of literature cannot be made due to the magnitude of the flaws in basic psychotherapy research methodology. Suggestions are made regarding the future of child and adolescent psychotherapy research. PMID- 1759997 TI - Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. AB - BACKGROUND: To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS: Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS: Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS: In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction. PMID- 1759998 TI - A management informatics rotation for pathology residents. AB - A formal, core, two-month rotation incorporating management concepts and computer usage has been instituted for residents in clinical pathology at Rush Medical Center. In this rotation, emphasis is placed on the pathologist's role as a laboratory director and decision maker and in the necessary computer skills and managerial background that must be acquired to make this role most effective. Specific behavioral goals and objectives were formulated for this rotation. The goals served as a guideline for the resident while involving each resident in the decision making process and in problem solving in day-to-day laboratory activities. The resident was encouraged to become familiar with the laboratory computer system, its operation, access, and reporting. Computer fundamentals were taught in instances where there was little or no prior computer experience. Management activities in which the resident was involved dealt with affirmative action, position searches, hiring and firing, laboratory accreditation, licensure laws, and decision making. This paper describes the rotation in detail and discusses each objective while incorporating both the resident's and laboratory director's perspectives. PMID- 1759999 TI - Erythropoietin for anemia of renal failure in sickle cell disease. PMID- 1760000 TI - Research on DNA typing catching up with courtroom application. PMID- 1760001 TI - Spiritual dimensions of health care. Nursing's mission. PMID- 1760002 TI - Improvement of functional sitting position for children with cerebral palsy. AB - Twenty-three children with cerebral palsy were photographed and video-filmed in six different sitting positions--including a hypothetical functional position- and the video-films and photographs were analysed. It was found that pathological movements were minimised and postural control and arm and hand function best when the child was sitting in a forward-tipped seat, with a firm backrest supporting the pelvis, arms supported against a table and feet permitted to move backward. PMID- 1760003 TI - Chronic-pain patients must cope with chronic lack of physician understanding. PMID- 1760004 TI - Sudden death in the young. AB - Sudden cardiovascular death in children and adolescents may occur without premonitory symptoms. Awareness of risk patterns can provide effective prevention in some cases. Antiarrhythmic therapy aimed at both atrial and ventricular tachyarrhythmias can reduce unexpected mortality. A major focus is curbing the risks faced by young athletes. Another is risk management after cardiac surgery. PMID- 1760005 TI - Hemoglobinopathies affect hemoglobin A1C measurement. PMID- 1760006 TI - Barriers to the treatment of obesity. PMID- 1760007 TI - Sickness dismissals--a management perspective. PMID- 1760008 TI - Use of enrofloxacin in laying birds. PMID- 1760009 TI - The war against drugs. PMID- 1760010 TI - Brittle diabetes. PMID- 1760011 TI - Non-operative management of blunt splenic injury. PMID- 1760012 TI - Essential hypertension: a sign in search of a disease. PMID- 1760013 TI - Lichen planus and liver disease. PMID- 1760014 TI - Acute intermittent porphyria in Bikaner. PMID- 1760015 TI - Pseudosickness and red cell casts. PMID- 1760016 TI - Treatment of abdominal aortic aneurysm by occlusion and bypass: an analysis of outcome. PMID- 1760017 TI - An excess of information. PMID- 1760018 TI - Surgeons who undertake surgery for colorectal cancer. PMID- 1760019 TI - Pethidine for painful crises in sickle cell disease. PMID- 1760020 TI - The long QT interval syndrome. A Rosetta stone for sympathetic related ventricular tachyarrhythmias. PMID- 1760021 TI - Crafting a viable health insurance system. PMID- 1760022 TI - Renal biopsy in nephrotic syndrome. PMID- 1760023 TI - PCR test for Chlamydia psittaci. PMID- 1760024 TI - 'The 5-year results of a clinical trial comparing a glass polyalkenoate (ionomer) cement restoration with an amalgam restoration'. PMID- 1760025 TI - Problems with the two stage analysis of crossover trials. PMID- 1760026 TI - Violence and sudden death. PMID- 1760027 TI - Psychotherapy research. PMID- 1760028 TI - Controversy in automated record keeping. PMID- 1760029 TI - Changes come to radiation regs; how will your facility be affected? PMID- 1760030 TI - Native Americans and the constant death instinct hypothesis. AB - To test Tabachnick and Klugman's hypothesis that the amount of death instinct per capita in different regions is constant, 1975-1977 death rates for motor vehicle accidents, cirrhosis, and suicide were obtained from the US Indian Health Service for all 11 health service areas. In contrast to predictions derived from the hypothesis that the death instinct is constant, no negative correlations were found among these three variables. Although an analysis of other behaviors might yield different findings, these results do not support an hypothesis of a constant death instinct among Indian Health Service regions. PMID- 1760031 TI - Cerebrospinal fluid rhinorrhea in patients with untreated pituitary adenoma: report of two cases. PMID- 1760032 TI - Easily avoidable hemolytic transfusion reactions after transfusion of frozen and washed autologous red cells. PMID- 1760033 TI - Diagnosing and differentiating a doubly committed ventricular septal defect from obstruction in the outflow tract of the right ventricle. PMID- 1760034 TI - A new pericardiocentesis set. PMID- 1760035 TI - Right bundle branch block induced by right ventricular involvement in inferior wall left ventricular acute myocardial infarction. PMID- 1760036 TI - Sensitivity and specificity of clinical tests. PMID- 1760037 TI - Delayed diagnosis of HIV-related tuberculosis. PMID- 1760038 TI - Why pediatric otolaryngology? PMID- 1760039 TI - Intragastric pH monitoring is unsuitable for diagnosis of duodenogastric reflux. PMID- 1760040 TI - Existence of bluish-white fluorescing age-pigment--"pre-lipofuscin". PMID- 1760041 TI - A response to Gostin, "The HIV-infected health care professional: public policy, discrimination, and patient safety". PMID- 1760042 TI - Haematological effects of reinfused mediastinal blood after cardiac surgery. PMID- 1760043 TI - Kidney transplantation from second-degree relatives. PMID- 1760044 TI - Craniosynostosis in the Ullrich-Turner syndrome. PMID- 1760045 TI - Composite multivariate quality control using a system of univariate, bivariate, and multivariate quality control rules. AB - We propose a composite multivariate quality control (CMQC) system to control simultaneously measured variables. This system is designed to detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure in any pair of variables. It is also designed to be tolerant of missing data, to be capable of rejecting as few as one or as many as all variables in a run, and to provide the analyst with control statistics and graphics that logically relate to sources of analytical error. Quality control rules for univariate, multivariate, and correlation conditions are incorporated in the system, as are plots displaying CMQC statistic values and control limits for univariate, multivariate, and correlation parameters. We also discuss advantages of the CMQC over the T2 and principal component multivariate quality control methods. We demonstrate the CMQC procedure using data from a laboratory process in which 40 variables were measured during 40 characterization runs and 23 runs analyzing unknowns. PMID- 1760046 TI - N-demethylation activity of renal and hepatic subcellular fractions: an interspecies comparison. AB - The enzymatic activity of the mixed-function oxidase system in the kidney and liver was evaluated by means of an in vitro N-demethylation activity assay with aminopyrine as the substrate. Renal and hepatic demethylation activity of 9000 x g supernatant fraction was determined in the rat, rabbit, and guinea-pig. In terms of interspecies comparison, the renal tissue demethylation activities were on a similar level with a slight increase in the order guinea-pig, rabbit and rat. In relation to hepatic activity, these relative demethylation activities of renal tissue had the same values in the rat and rabbit, whereas that in the guinea pig was significantly lower. The distribution of demethylation activity in the kidney was determined by comparing the cortex and medullary activity in relation to the total kidney tissue activity in the rabbit and guinea-pig. Although the higher demethylation activities were obtained in rabbit renal preparations and low demethylation activity was detected in the guinea-pig renal medulla only, no significant interspecies differences were found by the statistical evaluation. It may be concluded that the mixed-function oxidase system responsible for renal demethylation activity seems to be concentrated in the renal cortex and its distribution coincides in the rabbit and guinea-pig kidney. PMID- 1760047 TI - Colposcopes: a critical review. AB - A multidimensional professional team consisting of a practicing colposcopist, a mechanical engineer, and a medical photographer independently critically evaluated the features of selected colposcopes. Qualitative observations and quantitative measurements were performed on 13 colposcopes representing eight manufacturers and distributors. Optical characteristics, ocular system operation, mobility and stability, relative ease of use, component characteristics, space for instrumentation, and visual illumination, uniformity, and color were comparatively assessed. The specific colposcope information provided may benefit practicing physicians or novice colposcopists who are contemplating purchasing a colposcope. The presented framework of critical feature evaluation may also facilitate the informed selection of other colposcopes not included in this selective, critical, comprehensive review. PMID- 1760048 TI - Interpersonal aggressive behaviour and alcohol consumption among young urban adolescents in France. AB - In order to supplement existing studies of deviant populations (alcoholics, drug addicts, jailed delinquents) and to bring to light the existence of early relationships between aggressiveness and alcohol consumption, an epidemiological survey was carried out among 1601 adolescents (aged 13-16) from a suburban area of Paris. Some types of the aggressive behaviour studied were more socially acceptable--breaking objects, hitting people, fighting--than others--threatening to use or using physical violence to obtain money or objects from people. A majority of the adolescents had already demonstrated violent behaviour, 41% showed repetitive delinquent behaviour, and 12% cumulated several types of such behaviour. The aggressive teenagers differed from the non-aggressive subjects firstly in their alcohol, tobacco and illicit drug consumption, and secondly with respect to other deviant behaviour, such as stealing, running away from home or violent victimization. A logistic regression analysis highlighted the relative importance of each type of delinquent behaviour and of the early onset of regular alcohol consumption. The discussion focuses on the complex relationship between violence and alcohol consumption. PMID- 1760049 TI - The frequency of alcoholisation among young people injured in accidents in France. AB - In a nation-wide epidemiological survey carried out in France in 1982-1983, blood alcohol concentration was systematically measured in 1423 young casualties (aged 15-24 years) on their arrival in the emergency room. Traffic accidents accounted for almost half of the admissions, and they were the most severe, with over 10% requiring hospitalisation with vital risk. A quarter of the admissions was female; on average, their blood alcohol concentration was low and not statistically related to age. Conversely, among young male casualties, 1 out of 5 had a blood alcohol concentration of at least 0.50 g/l (11 mmol/l) and 1 out of 15 was classified as a chronic heavy drinker. It is of note that alcohol was implicated in 43% of the car/truck accidents of the young men and that blood alcohol concentration as well as the proportion of chronic drinkers were strongly related to age. Alcohol consumption may begin as early as 15 years; in the young men 15-24 years, only 7% were chronic drinkers whereas in men over 24, 37% were chronic drinkers. On this basis, it is appropriate to focus education about alcohol consumption on adolescents, particularly men. PMID- 1760050 TI - The 'topping-up' effect: differences between low- and non-alcoholic lager on blood ethanol. AB - The peak blood alcohol levels attained in male and female subjects after consumption of 3 pints of regular lager (4.2%) over a 30 min period was 73.5 +/- 6.9 mg% in males and 113 +/- 17 mg% in females. Peak values occurred at 60 and 90 min post-ingestion in males and females, respectively. Consumption of 3 pints of low-alcohol lager gave a maximum blood alcohol level of 13 mg% while there was no measurable blood alcohol content after three pints of non-alcohol lager. 'Topping up' with a non-alcohol lager after 2 pints of regular lager leads to significantly lower blood alcohol levels when compared with 'topping-up' with low alcohol lager over a comparable time in males but not in females. PMID- 1760051 TI - Evidence that gonadal hormone levels in amniotic fluid are decreased in males born to alcohol users in humans. AB - Biochemical evaluation of amniotic fluid content is often used to monitor fetal secretory and excretory functions. It is known that alcohol freely passes through the placenta and enters the fetal tissues. The study was designed to investigate whether alcohol use during pregnancy affects amniotic fluid steroid and peptide hormone levels. Five alcohol users who drank between 40 and 45 drinks per month and consumed approximately 1 oz. of alcohol per day from beer drinking participated in the study. Thirteen controls with no history of alcohol use including essential and non-essential drugs were selected for the study. The final selection of participants was made among those who delivered male offsprings. Amniotic fluid was aspirated between 16 and 20 weeks of gestation by amniocentesis and an aliquot was used to assay steroid hormones (4 androstenedione [-4-AD], testosterone [T], estradiol [E2], dehydroepiandrosterone sulfate [DHEA-S]), and peptide hormones (FSH and LH). Birth weights, placental weights and gestation age were recorded at birth. The results showed that -4-AD, T and E2 levels were significantly decreased (P less than 0.01) in alcohol users; DHEA-S, FSH and LH levels were unaffected. Birth weights were significantly decreased (P less than 0.05) in alcohol users, the placental weights and gestation age were not affected. We conclude that alcohol passes through the placenta and affects fetal testes, capacity to synthesize steroids and the effect appears to be direct and not via the hypothalamic-hypophyseal axis. PMID- 1760052 TI - Platelet monoamine oxidase activity in type 1 and type 2 alcoholism. AB - Earlier studies have identified at least two distinct subtypes of alcoholism. Type 2 is characterised by high heritability, early onset, frequent social complications and mixed misuse. With regard to temperament, the type 2 alcoholics score high in impulsiveness and sensation-seeking behaviour. Type 1 alcoholics have a later onset, lower degree of heritability and rarely there is misuse of illegal drugs. In the present study, 37 type 1 and 62 type 2 male alcoholics were compared with 36 male controls with regard to platelet monoamine oxidase (MAO) activity, which is a stable biological marker, inversely correlated to personality traits such as impulsiveness and sensation seeking. The platelet MAO activity was found to be lower in type 2 alcoholics when compared both with healthy controls and with type 1 alcoholics. Also, the type 1 alcoholics had lower platelet MAO activity than the controls. The result confirms a previous study and validates the subclassification of alcoholism according to the type 1 and 2 concept. This should be of value for future studies concerning etiology, epidemiology, treatment and prevention of alcoholism. PMID- 1760053 TI - HLA Gm systems and susceptibility to alcoholic cirrhosis: a study of mixed-race subjects. AB - The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak. PMID- 1760054 TI - Effect of heavy drinking and alcohol withdrawal on markers of carbohydrate metabolism. AB - A number of biochemical markers were monitored in 38 male alcoholic patients at admittance and one week later. In patients with a drinking period of greater than 3 weeks the median fasting B-glucose decreased significantly as well as S fructosamine concentrations. The ability of S-fructosamine to identify patients with a diabetic glucose tolerance test, expressed in terms of sensitivity and specificity, was 12 and 47%, respectively; that of HbA1c was still lower. PMID- 1760055 TI - Detection of stable acetaldehyde-modified proteins in the livers of ethanol-fed rats. AB - Liver cytosolic fractions, obtained from rats pair-fed diets supplemented with either ethanol or an isocaloric amount of sucrose for periods from 3 weeks to 27 months, were tested for the presence of acetaldehyde-modified proteins by immunoblotting, using a partially purified antiserum raised in rabbits against proteins modified by acetaldehyde in vitro. The antiserum reacted with a large number of proteins in cytosolic fractions from ethanol-fed rats but did not react with any proteins in the same fraction from control animals. The duration of the ethanol-containing diet did not appear to influence the number of proteins modified or the total amount of modification within the time range tested. These results indicate that many proteins in rat liver cytosol are targets for modification by acetaldehyde in vivo. PMID- 1760056 TI - Pattern of the adaptive response of erythrocyte glycerolipid acylation processes during chronic alcoholism. AB - Challenging intact erythrocytes from normal human subjects with ethanol resulted in dose-dependent decreases in rates of acylation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while triacylglycerol (TAG) acylation was stimulated. In erythrocytes from alcoholic subjects, the responses were of lesser magnitude, indicating a lower sensitivity to ethanol. This in vitro resistance, typical of the state of tolerance, was associated in erythrocytes from alcoholic subjects with increased baseline rates of acylation of PC, PE and TAG, suggesting high levels of glycerolipid fatty acid turnover. These results suggest that (1) intact human erythrocytes are qualitatively and quantitatively valid for studying the adaptive response to ethanol; and (2) chronic alcoholism is associated with increases in turnover rates of the acyl moieties of lipid membrane components regardless of the pattern of initial sensitivity to ethanol. Increased acylation rates during chronic alcoholism might modify the remodeling of the lipid matrix and thereby the membrane function. PMID- 1760057 TI - The effects of chronic ethanol administration on rat liver and erythrocyte lipid composition: modulatory role of 'evening primrose oil'. AB - The effects of chronic administration of ethanol on the lipid composition of erythrocytes and liver of rats were investigated. Ethanol was chronically administered alone or in combination with Evening Primrose Oil (containing 10% v/v gamma-linolenic acid) in a nutritionally balanced milk diet. Chronic administration of ethanol alone significantly decreased the content of arachidonic acid in erythrocyte membranes, whereas the concomitant administration of Evening Primrose Oil reversed this effect. The triacylglycerol content was significantly increased in the microsomal fraction of the liver after chronic ethanol administration. Ethanol also significantly increased the ratio of cholesterol:cholesteryl esters in the microsomal fraction. The arachidonic acid content of the whole liver fraction was significantly reduced after chronic administration of ethanol, whereas concomitant administration of Evening Primrose Oil did not reverse this effect. The administration of Evening Primrose Oil during chronic ethanol intake may have beneficial effects, as it reverses some of the effects of ethanol on erythrocyte and hepatocyte membrane lipids which may be detrimental to health. PMID- 1760058 TI - The effects of dietary lead on ethanol-reinforced responding. AB - Sixteen adult male rats were presented with a diet containing no added lead (Group Control) or a diet containing 500 ppm inorganic lead (Group Lead) for 60 days. Subsequently, all animals were trained to lever press on an FR 1 reinforcement schedule for an ethanol reinforcer using a food-induction procedure where 20 g of food were presented to deprived animals 1 hr prior to the training session. Gradually, the daily food allotment was shifted to 15 min post-session and the ethanol concentration maintained at 6% (v/v). On a subsequent dose/response test, serial presentations of 1, 2, 4, 8, 16, and 32% ethanol reinforcement (v/v) were presented to both groups of animals. The results from the initial self-administration test using 6% ethanol as the reward outcome showed that Group Lead lever pressed at a significantly lower rate than Group Control. In addition, on the dose/response test control animals increased responding at a lower concentration, and then as dose levels continued to increase, began to decrease responding earlier than lead-treated animals. Apparently, sensitivity to ethanol effects is decreased by lead toxicity. The importance of these data for understanding other metal/alcohol interactions is discussed. PMID- 1760059 TI - Comments on Tittmar's 'limits of confidence in statistics'. PMID- 1760060 TI - Misdiagnosis of a normal fetal platelet count after coagulation of intrapartum scalp samples in autoimmune thrombocytopenic purpura. AB - Intrapartum fetal scalp sampling for platelet counts in maternal autoimmune thrombocytopenia has been advocated for determining route of delivery. We report a case in which two coagulated scalp samples were believed to indicate a normal fetal platelet count. As a result, vaginal delivery of a severely thrombocytopenic fetus was allowed. PMID- 1760061 TI - Evaluation of phenazopyridine hydrochloride as a tool in the diagnosis of premature rupture of the membranes. AB - This is a prospective study to determine whether a maternal orally administered azo dye, phenazopyridine hydrochloride, would cross into amniotic fluid, and thus be of potential aid in the diagnosis of rupture of the membranes. Based on anecdotal experience, we hypothesized that this compound would cross the placenta and be excreted in the fetal urine, causing discoloration of the amniotic fluid. Ten patients with uncomplicated pregnancies undergoing elective amniocentesis for obstetric indications received an oral dose of 400 mg of phenazopyridine hydrochloride 4 hours prior to the procedure. Amniotic fluid was also available from five control patients who did not receive phenazopyridine hydrochloride. The typical orange-to-red discoloration of the urine was seen in all study patients, indicating ingestion of the dye. None of the ten patients had evidence of the azo dye in their amniotic fluid by visual inspection or by spectrophotometric absorbance. After the amniotic fluid samples were acidified, the presence of the azo dye was visually demonstrable, and spectrophotometry confirmed measurable concentrations (mean +/- SE: 13.08 +/- 0.72 micrograms/ml). We conclude that although phenazopyridine hydrochloride does cross the placenta into the fetal compartment, its presence causes a visual and spectrophotometric change in the color of amniotic fluid only when the normal basic pH of amniotic fluid is acidified. PMID- 1760062 TI - Hypoxic pulmonary hypertension: changes in platelet size and number. AB - Circulating platelets have been implicated in the hypoxic pulmonary pressor response. This study was undertaken to assess the effects of acute hypoxia induced pulmonary hypertension on platelet volume and number across the pulmonary circulation in anesthetized newborn lambs. Seven animals were instrumented for measurement of pulmonary vascular resistance. All measurements were made during normoxia and after 5 and 30 minutes of hypoxia (10 to 12% oxygen breathing). Hypoxia caused a doubling of the pulmonary vascular resistance. During hypoxic vasoconstriction, platelet volume decreased rapidly while traversing the lung but was not affected on return to the lung after traversing the systemic circulation. Platelet numbers were unchanged on leaving the lung but were decreased on entering the lung during hypoxia. Our data are consistent with the release of platelet contents in the lung during hypoxic pulmonary hypertension. PMID- 1760063 TI - Hyperstimulation contraction stress tests: an evaluation of outcome by test pattern. AB - Contraction stress tests (CSTs) interpreted as equivocal, with hyperstimulated contractions accompanied by late decelerations (hyperstimulation CSTs), were analyzed by test pattern and outcome and compared to a control group with negative CSTs. Outcome was evaluated for subsequent abnormal CST, low Apgar score, the presence of meconium, and cesarean section for fetal distress. Patients with hyperstimulation CSTs and solitary late decelerations, and the remainder of the test interpretable as a negative CST, had the least morbidity. In both the presence and absence of 10-minute negative windows, patients with more than one late deceleration were at significantly higher risk for cesarean section for fetal distress than controls. It would seem warranted in the presence of hyperstimulation CSTs, therefore, to repeat the CST within 24 hours regardless of the presence of a negative window. PMID- 1760064 TI - A review of newborn medicine in America: European past and guiding ideology. AB - The beginnings of newborn medicine and its rapid advance in America since the early twentieth century are reviewed through presentation of ideas that have influenced the givers of care. Newly born infants attained patient status at the end of the 19th century when Budin gave them hospital charts and Ballantyne designed the blueprint for continuity of maternal-infant care. These achievements gave impetus to the task of preserving infant life. In 1915, the United States established a birth registration area permitting calculation of infant mortality rates. These rates became the guide and yardstick for measuring progress in newborn care. Since 1915 infant mortality has decreased tenfold as survival increased successively in the postnatal infant, the neonate, and recently in the premature. Pediatricians began to supervise newborn nurseries after World War I. During depression years, national efforts were expended for the premature. After World War II, pediatricians moved close to birth, assessing and treating in the delivery room. Special care and intensive care nurseries sprang up in the 1960s. In the past 25 years, improvements in ventilation and life support systems have enhanced survival of compromised and immature infants. Today, newborn medicine is spectacularly successful in lowering neonatal mortality but is beset by costs, ethics, legal concerns, and the burden of survival morbidity. Controversy such as exists today is not new to newborn medicine; it has been its constant companion throughout history. PMID- 1760065 TI - Noninvasive medical management of fungus ball uropathy in a premature infant. AB - Unilateral renal obstruction secondary to fungus balls is described in a premature infant. Noninvasive medical management, which included amphotericin B and 5-flucytosine therapy and forced diuresis, resulted in disappearance of fungus balls and resolution of the obstruction. PMID- 1760066 TI - Management of triplet pregnancies in the 1980s--are we doing better? AB - The incidence of triplet pregnancies has increased with the introduction of ovulation induction agents and is expected to further increase with the implementation of multiple embryo transfer in the in vitro fertilization programs. We review our experience with 29 triplet pregnancies in the last 10 years. Despite early sonographic diagnosis, close follow-up, increased use of tocolytics, and prophylactic cervical suture, we could not document prolongation of pregnancy, increased infants' weight, or a significantly decreased perinatal mortality, which still remains about 14%. Furthermore, the use of cesarean section as the delivery method of choice did not change the well-documented unfavorable relationship between birth order and fetal outcome. There is an urgent need for prospective assessment of the value of different treatment modalities, which nowadays becomes possible with the increasing incidence of triplet pregnancies. The prevention of triplet pregnancies or treatment by selective fetal reduction deserves a second thought. PMID- 1760067 TI - Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact. AB - Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally. PMID- 1760068 TI - Sonographic evaluation of growth discordance and chorionicity in twin gestation. AB - Ninety-four twin gestations had serial ultrasound examinations for evaluation of fetal growth, with special attention to prediction of weight discordance and chorionicity. Fetal weight estimations were made a mean of 3.2 days before birth and then compared to actual birthweights. The average error in intertwin discordance prediction was 1 +/- 9%. In 56 patients ultrasonic detection of membrane thickness was compared with placental pathologic conditions. If a membrane was seen between twins, it was confirmed by placental pathologic study in all cases. No membrane was seen in four twin pairs, but only one of these actually had monochorionic monoamniotic membranes. The three cases with false positive diagnoses of monoamniotic twin gestation were initially seen late in pregnancy. If clinical decisions in twin gestations are based on ultrasound determination of discordance and chorionicity, the level of accuracy demonstrated by these data must be considered. PMID- 1760069 TI - Sonographic verification of a nuchal cord following a vibratory acoustic stimulation-induced severe variable fetal heart rate deceleration with expedient abdominal delivery. AB - A case is presented in which external vibratory acoustic stimulation performed following a nonreactive nonstress test produced a severe variable deceleration of the fetal heart rate. A clinically suspected nuchal cord was confirmed by ultrasound. This rapid precise antepartum diagnosis of cord compression prevented untimely delay and led to immediate abdominal delivery of a nonacidotic, yet hypoxic, infant. This report suggests care be taken when fetal vibratory acoustic stimulation is applied in cases of oligohydramnios and a known existing nuchal cord. PMID- 1760070 TI - Risk factors associated with preterm deliveries among racial groups in a national sample of married mothers. AB - Seven sociodemographic and behavioral factors that may explain the increased risk of preterm deliveries among black women were examined using data from a national sample of 5823 married mothers who responded to the 1980 National Natality Survey (NNS) Questionnaire. There was a twofold increase in the rate of preterm deliveries among black women. Additionally, there was a significant decrease (by 1 week) in the mean gestational age in black mothers (p less than 0.0001) compared with white mothers. The two groups were similar with respect to smoking and age; however, there were significant differences between the two groups with respect to other risk factors. Black women had a higher rate of heavy alcohol use, significantly fewer prenatal visits, prenatal care was started later during pregnancy (p less than 0.0001) and were less educated compared with white women. The odds ratio (OR) for race adjusted for the risk factors was 1.56 (95% confidence interval (CI) equals 1.21, 2.01). All other risk factors except education had adjusted ORs greater than 1. Those risk factors that were more strongly associated with the risk of preterm births included weight gain (OR, 2.10; 95%, 1.79, 2.47), number of prenatal visits (OR, 3.37; 95% CI, 2.87, 3.95) and smoking (OR, 1.34; 95% CI, 1.13, 1.59). We conclude that race is an independent risk factor for preterm deliveries. Additionally, it is shown here that the risk of preterm deliveries is attributable to health behaviors that are amendable to change. PMID- 1760071 TI - Imaging case of the month: I. Teratoma of the newborn. PMID- 1760072 TI - Imaging case of the month: II. Central diaphragmatic hernia with herniation of the liver into the pericardial sac. PMID- 1760073 TI - The circumpolar community. PMID- 1760074 TI - Local cold injuries sustained during military service in the Norwegian Army. AB - The series comprises 40 soldiers who sustained 49 local cold injuries during their service in The Norwegian Army. Twenty-one cold injuries were classified as first degree, 15 as second degree and 13 as third degree. No difference in ambient temperature at the time of injury was observed between the three categories of injuries, but the duration of cold exposure was significantly longer in those suffering third degree injury. Thirty-eight of the 40 soldiers experienced sequelae. The trend was that the severity of sequelae was most pronounced in third degree injuries. However, soldiers with first degree injury may suffer from significant sequelae, while those with third degree injury may exhibit a more benign clinical course. Overall degree of distress from sequelae was mild to moderate with exacerbation of symptoms and signs upon cold exposure. Although the influence on civilian occupational activity was minor, a substantial negative impact on performance in the field or combat setting may be anticipated. Soldiers as well as commanders must be thoroughly informed about prophylactic measures, symptoms and signs of an impending cold injury. Rewarming of the skin must be initiated without delay. PMID- 1760075 TI - Haptoglobin levels among alcoholics in Alaska. AB - The levels of haptoglobin, plasma proteins and amino acids were studied in a non fasting population of alcoholics. In 25 subjects, only small differences were seen between the means when Native subjects were compared to non-Native. There did not appear to be any acute phase response differences between these two groups. This study did not substantiate other reports on the correlation of the severity of alcoholism with glycoprotein synthesis. PMID- 1760076 TI - Conception of man and the preservation of his health in circumpolar regions. AB - The preservation of human health in polar and circumpolar regions depends mainly on the strategy for future development of these regions. The consequences of human intervention into northern ecology are irreversible, as in the case of the greenhouse effect, the industrial and atomic pollution of polar nature, the tundra devastation, the destruction of northern flora and fauna etc. The ongoing creation of large industrial population centres in the North by means of newcomers is to be stopped. Polar regions are to be used for biospheric reservation and tourist sanitary zones, to preserve specific flora and fauna, to provide the rhythms and customs necessary to survive in extreme climatic and geophysical conditions of high latitudes. The program for securing man's survival in circumpolar regions should comprise several stages of practical measures to provide necessary resources and to combine international efforts. The preservation of man's health must be based on the understanding of the interrelation between health and biospheric processes and the assessment of the role of human intervention into polar ecology. A program facilitating the preservation of human health and survival in the North and in the Antarctic should be initiated. PMID- 1760077 TI - The epidemiology of viral hepatitis. PMID- 1760078 TI - Epidemiology of viral hepatitis in circumpolar populations. PMID- 1760079 TI - Treatment of viral hepatitis. PMID- 1760080 TI - Prevention of viral hepatitis--immunoprophylaxis. PMID- 1760081 TI - Prevention of viral hepatitis in circumpolar populations. PMID- 1760082 TI - The neurophysiological basis of epileptic activity: a condensed overview. PMID- 1760083 TI - Circadian distribution of generalized spike-wave activity in relation to sleep. PMID- 1760084 TI - Nocturnal paroxysmal dystonia. PMID- 1760085 TI - Sleep polygraphic findings in epileptic encephalopathies from infancy to adolescence. PMID- 1760086 TI - Sleep and prolonged epileptic activity (status epilepticus). AB - The correlations between sleep and prolonged epileptic activity are discussed on the basis of the status classification of Gastaut (1983). Little information is available on the interrelation of sleep and the status of tonic-clonic seizures (grand mal status). Most important is the therapeutical management of these cases. Tonic seizures have been reported to occur in large numbers during NREM sleep in patients with Lennox-Gastaut syndrome. A status-like increase is possible. Tonic seizures occur almost exclusively during sleep. Myoclonic status epilepticus arising (a) in the course of primary generalized epilepsy and (b) in the course of encephalopathies, are usually markedly attenuated during sleep. In absence status (petit mal status) synchronized sleep generally fragments the continuous discharge which is replaced by isolated bursts of polyspikes, or polyspike and wave complexes. The absence status can recur upon awaking during the night or in the morning. The abnormal EEG activity of a petit mal status can, however, occasionally persist during the whole night. Improvement as well as activation during sleep have been observed in elementary (= simple) partial status epilepticus; improvement seems to be more frequent. Epilepsia partialis continua may persist or decrease during sleep. An increase as well as decrease of motor phenomena has been observed during the REM stages. 'Epileptic aphasia' of childhood is associated with subclinical bioelectric status epilepticus during sleep. The electrical status epilepticus must be delineated as a separate group. The term encephalopathy related to electrical status epilepticus during slow sleep (ESES) has been proposed on the basis of associated psychic syndromes. This form of status epilepticus disappears during the waking state and during REM sleep. Cases with hypsarrhythmia without clinical signs may also be classified under the group of electrical or bioelectrical status. In some cases, a continuous hypsarrhythmia is observed only during sleep. In this context, one must also mention those patients who demonstrate continuous activation of spikes, or spike and wave potentials (without clinical seizures) during eye closure. PMID- 1760087 TI - Integrated sleep analysis, with emphasis on automatic methods. PMID- 1760088 TI - Historical aspects of sleep and epilepsy. PMID- 1760089 TI - General considerations of sleep and sleep deprivation. AB - The state of affairs in the field of sleep deprivation has been discussed in this chapter. Special emphasis was placed on total sleep deprivation, a domain in which the most important work has been done since the dawning of this century, and especially during the 'golden years' between 1955 and 1975. After a discussion of the biorhythmical aspects, the general condition of sleep deprived subjects was pointed out. Psychological-psychiatric changes and impairment of performance were further topics of discussion, followed by sections on EEG, neurological, autonomic and metabolic changes. The relationship of SD to epileptic phenomena and endogenous depression has been considered. The characteristics of recovery sleep have also been presented. Most of the author's impressions are based on personal data, and especially on 2 subjects who underwent most elaborate testing. A discussion of partial sleep deprivation and selective sleep deprivation is also included. PMID- 1760090 TI - Short-term sleep EEG recordings after partial sleep deprivation as a routine procedure in order to uncover epileptic phenomena: an evaluation of 719 EEG recordings. AB - All night sleep deprivation prior to an EEG registration causes some inconvenience not only to the organization of the EEG department but presents a burden on the patients as well as their family members, and for these reasons is not suitable to be frequently employed as a routine procedure. As an alternative, we performed short-term sleep recordings in the early afternoon following a partial sleep deprivation of the patients during the preceding night. This method was well accepted by the patients and their family. Our only goal was to shorten the total time of night sleep using the following guideline: for very small children 22.00-06.00; for 4-14-year-old patients 24.00-06.00; and for patients older than that 01.00-06.00. 79.9%, out of 719 patients (573) who had been given the above instructions subsequently showed sleep patterns in their EEG. Additionally we had to administer an oral dose of promazine to only 67 patients. However, for the most part, patients showed only light sleep stages: 114 patients only reached sleep stage 1; 323 patients sleep stage 2; 88 patients sleep stage 3; and 48 patients sleep stage 4. As expected, REM sleep was never recorded. Nonetheless, in 32 out of 146 patients who were tired but unable to fall asleep, epileptic patterns could be provoked. In 636 patients, the EEG-recording after sleep reduction was ordered because of a suspected seizure disorder; in the remaining patients it was initiated solely because of sharp components in the routine-EEG. In 341 (53.6%) of the patients with suspected epilepsy, electroencephalographic activity indicative of a seizure disorder was activated. Such epileptic patterns were recorded almost exclusively in stages of waking, 1 and 2. Only in one out of the 124 patients who reached sleep stages 3 and 4 epileptic patterns were not seen until deep sleep was entered. We observed 2/s, 3/s and 6/s spike-and-wave complexes, sharp waves, spikes, polyspikes, groups containing remarkably sharp components and so called sharp vertex grapho elements. Patients with suspected seizure disorders frequently show grapho elements which can be interpreted as the expression of a disposition for epilepsy. These sharp vertex elements were evident in 54 out of 719 short term sleep recordings, more often in children than in adults. 49 times they coincided with typical epileptic discharges such as sharp waves, spikes or spike-and-waves in the same recording. PMID- 1760091 TI - Sleep and epileptic activity. AB - Thirteen patients suffering from severe partial epilepsy and potential candidates for surgical treatment were investigated with stereotactically implanted intracerebral electrodes during nocturnal physiological sleep. The recorded electrocerebral activity was automatically analyzed to gain information on interictal epileptic events during wakefulness and the phases of sleep. The interictal epileptic activity shows: (1) great variability in the different subjects, and intra-individually, variability according to the explored cerebral regions; (2) is not influenced by the location of the recorded epileptic events; and (3) is affected by the local level of epileptogenicity. The latter was determined by the assessment of the capacity to give origin to ictal discharges and the disappearance of seizures following surgical removal. The interictal rate of spiking from the most epileptogenic cerebral zone is characterized by a relative stability during the night and by a relatively high degree during REM sleep. PMID- 1760092 TI - The nature of the influence of sleep deprivation on the EEG. PMID- 1760093 TI - Sleep and sleep deprivation in epileptology. PMID- 1760094 TI - Sleep deprivation, epilepsy and the ability to operate a motor vehicle. AB - This study is based upon 207 examinations for the evaluation of the ability to operate a motor vehicle in persons with transient disturbances of the cerebral function. In 26 persons, the EEG was repeated after sleep deprivation. There was EEG activation with transient disturbances in seven cases (not present in the routine EEG). In five individuals, there were transient disturbances in the routine EEG as well as after sleep deprivation. No abnormalities were recorded in 14 persons. No driver's license could be granted in five patients with unequivocal spike wave complexes or spike wave paroxysms following sleep deprivation. In two patients, however, the permission to drive could be granted. These patients showed spike wave patterns in the routine EEG, but no seizures had occurred for several years and their performance in the experimental psychological evaluation (with simulator) were superior. In persons with suspected and clinically obscure cerebral attacks, as well as in persons with known seizure disorder but seizure-free for several years, the EEG after sleep deprivation must be regarded as a highly informative test which may crucially influence the decision. The method of activation corresponds with a type of stress with which the motorist must deal frequently. This test can be carried out on an outpatient basis and with negligible iatrogenic damage. PMID- 1760095 TI - Sleep deprivation and epileptological implications. PMID- 1760096 TI - Suppressive effects of enkephalins and REM sleep deprivation on seizures. PMID- 1760097 TI - The enforced nap: a simple effective method of inducing sleep activation in epileptics. AB - The authors routinely carry out sleep activation in suspected cases of epilepsy when the EEG performed in the waking state gives insufficient data. The technique used, referred to as 'the forced nap', allows the induction of 60 min sleep in 80% of all subjects and 90% of those under 16 years of age. This method gives results comparable with (and probably better than) those obtained by EEG recording after 24 h sleep deprivation, but is much simpler to carry out and can be used by all hospital-based EEG laboratories. The widespread use of this method should allow to change the current situation. It was found that more than 50% of hospital-based EEG laboratories do not perform sleep activation, and the remaining centers restrict this technique to a very limited number of patients, thus depriving almost all epileptics of an effective diagnostic tool. PMID- 1760098 TI - Awakening epilepsy ('Aufwach-Epilepsie') revisited. AB - The concept of 'awakening epilepsy' (introduced by Janz, 1953) occupies a crucial position for the comprehension of primary generalized epilepsy. The associated electroencephalographic manifestations are discussed and the role of abnormal (paroxysmal) arousal responses ('dyshormia') is stressed. The origin of these bilateral-synchronous discharges appears to be located below the frontal midline scalp region in mesial portions of the supplementary motor region. 'Awakening epilepsy' is also interesting from the viewpoint of sleep research. There is also an important age factor; these seizures (mostly grand mal and classical petit mal absences) are most common in older children, adolescents and young adults. The general management of these patients has to take into account the patient's special vulnerability after a night of poor sleep. PMID- 1760099 TI - Sleep organization and epilepsy. AB - Sleep is known to facilitate epileptic manifestations but can also protect the sleeper against the recurrence of seizures. This has been demonstrated in studies on sleep deprivation, and is particularly evident in alcoholic epilepsy and matutinal myoclonus epilepsy. Sleep organization in the epileptic patient is permanently altered by frequent awakenings and stage shifts. Nocturnal grand mal and repetitive partial seizures worsen the sleep disorder by reducing total sleep time and decreasing REM percentage by half. The cumulative effect of these sleep disorders may act on day-time vigilance in epileptics, and may even exert an influence on the recurrence of seizures. PMID- 1760100 TI - Sleep and benign partial epilepsies of childhood: EEG and evoked potentials study. AB - The electroclinical picture and nosological limits of benign partial epilepsy of childhood with rolandic spikes (BERS) have been better defined by nocturnal sleep records. In all stages of sleep, there is a significant increase in frequency and amplitude of rolandic spikes (RS) without change of their morphology. Another interesting observation is the appearance of independent spike foci in sleep, or brief subclinical spike wave discharges which are limited to the state of drowsiness. More recently, other types of partial epilepsy of childhood with benign evolution have been identified: (a) partial epilepsy with induced spike representing somatosensory evoked potentials; (b) benign psychomotor epilepsy; (c) partial epilepsy with occipital spike waves. In all these forms, the sleep records are essentially similar to those in BERS and have been very helpful in the nosological identification of these forms of epilepsy. For this reason, the sleep records of these special forms are truly informative for the clinician from the diagnostic and prognostic viewpoint. On the other hand, some investigators, have pointed out that, in the initial stage of these benign forms of partial epilepsy, there may be more or less significant intellectual impairment and behavioral disorder, sometimes accompanied by frequent brief absences. From the EEG viewpoint, this condition is characterized by brief discharges of slow spike wave complexes amounting to a pattern of "electrical status epilepticus". This special electroclinical condition mimics the Lennox-Gastaut syndrome but is generally self-limited. Thus, a correct differential diagnosis is very important from the diagnostic viewpoint. There is good evidence that sleep records permit an earlier identification of these conditions and strongly contribute to a correct differential diagnosis. In the benign partial epilepsy the SEPs, during awake and sleep, morphology and latency are normal, while the N60 amplitude is increased. A group of children with benign partial epilepsy shows EEG spikes evoked by tapping, and giant N60 component. This giant component persists during sleep and is not specific for any type of benign partial epilepsy. In conclusion, the results of sleep recordings are conducive to a correct diagnosis and better definition of the nosological delineation of partial epilepsies in childhood; they also provide a better comprehension of their evolution, and thus of their prognosis. The Evoked Potentials seem be a useful tool in the study of benign partial epilepsy. PMID- 1760101 TI - Epileptic manifestations and influence on sleep in the baboon Papio papio. PMID- 1760102 TI - Temporal lobe epilepsy, sleep and arousal: stereo-EEG findings. AB - By means of combined surface and depth EEG recordings (32 channels) and split screen video-monitoring (infra red light), complete all-night sleep studies were carried out in drug-resistant epileptics suffering from complex partial seizures. These data were supplemented by (1) all-night sleep recordings from three patients who had chronically implanted electrodes in the periaqueductal grey matter because of severe pain problems, and (2) incomplete sleep recordings (day time or only partial night) from other drug-resistant epileptics, who underwent chronic stereo-electroencephalographic (SEEG) examination in view of the surgical therapy. The following questions of importance were studied and the results were compared between different patient groups. 1. Relationship between overt clinical seizures or subclinical seizure discharges and the time course of night sleep. 2. Topic behavior of the epileptogenic area and different propagation phenomena of interictal spikes and ictal seizure discharges in different sleep stages. 3. Influence of arousal on the average spike incidence of any location with special attention to the different (slow and fast) components of the K-complex and their association with spiky elements, thus testing the hypothesis that the K-complex might serve as a vehicle for the seizure discharge. 4. Incidence and time relationship of seizure discharges with clinical overt awakenings. PMID- 1760103 TI - Incidence of medically treated burns in The Netherlands. AB - During the period January 1988 to December 1989, medically treated burn injuries in The Netherlands were recorded prospectively by three registration systems. These systems cover patients treated in burn units, in general and university hospitals, and by general practitioners. Incidence rates and 95 per cent confidence intervals were calculated, and basic epidemiological data about severity and localization of the burns and about accident circumstances were collected. The overall incidence rate of medically treated burns over all levels of medical care is estimated to be about 280 per 100,000 persons per year. This overall incidence figure appeared to be about three times as high for 0-4-year old children: 775 per 100,000 per year. At all levels of medical care, scalds are the most frequent type of burn, resulting in an overall incidence rate among 0-4 year-old children of 430 per 100,000 per year. Incidence rates are lowest among the elderly (55 years and over), but this age group suffers a higher mortality from burns. Furthermore, it appeared that males are more prone to serious burns than females, whereas female are more often treated for less severe burns. Most of the accident circumstances for serious burns were related to professions, whereas most of the circumstances for less severe burns were related to household activities. PMID- 1760104 TI - Determinants of behavioural risk factors for burn injuries. AB - Systematically developed health education should be based on a thorough knowledge of the determinants of the behavioural risk factors. Compared to other health related behaviours, safety behaviour has some specific characteristics, which complicate studying its determinants. First, there is a multitude of circumstances leading to injuries, which means that it is not possible to pinpoint one desired behaviour to be linked with the prevention of injuries. Secondly, people are often not familiar with (the advantages and disadvantages of) all the possible preventive measures. Thirdly, the usefulness of preventive measures may depend on housing situations. So far, no elegant way of coping with these problems in examining the determinants of safety behaviour seems to have been suggested in the literature. In this article an approach to the study of determinants of safety behaviour is presented. The general description of this approach is illustrated by a study on the determinants of the behavioural risk factors for burn injuries in young children, which was conducted among Dutch and Turkish parents of children aged 0-4 years. The results indicate, for instance, that parents who implemented the safety behaviour reported that safety behaviour had become habitual to them. PMID- 1760105 TI - Gastrocnemius acetylcholinesterase activity in response to burn trauma in the mouse. AB - In this study we examined the effect of increasing size of body surface area (BSA, 20, 30 and 50 per cent) burn on distally located gastrocnemius acetylcholinesterase (AChE) activity. Burn injury was applied to predefined areas of the dorsal and ventral skin surfaces of mice. AChE activity at 3 weeks postburn was measured by differential extraction and velocity sedimentation on sucrose gradients. Analysis of variance was used for all statistical evaluation. Within the sham-treated controls most of the AChE activity consisted entirely (92 per cent) of the globular forms (S1 and S2). Asymmetric (S3 and S4) and non extractable (H5) forms were 2 and 5 per cent, respectively. The total globular, asymmetric and non-extractable forms were not significantly different in gastrocnemius among the burn groups. However, individual forms (6.5S, 10S) of the soluble globular group (S1) were decreased (P less than 0.05) by half for all burn groups. Some molecular forms (4S, 10S) of residual globular group (S2) were decreased (P less than 0.05) in the 20 per cent and 50 per cent burn groups. In the asymmetric group (S3) the molecular forms (4S, 10S, 12S and 16S) were increased (P less than 0.001) for the 20 and 30 per cent groups. Within and between extraction groups interrelationships of the molecular forms were apparent. These data provide evidence that in response to burn trauma AChE activity of the gastrocnemius showed a decrease in soluble globular and an increase in asymmetric forms with multimeric dependence. PMID- 1760106 TI - Cryopreservation of cultured skin cells. AB - Cryopreservation of human skin keratinocytes and fibroblast cells has been evaluated using three cryoprotectants at various concentrations, three cooling rates and two warming rates. Optimal combinations of factors were determined. Selection for tolerance to cryopreservation was not detected after repeated freeze/thaw cycles. A beneficial effect of serum was shown to be cooling rate dependent. PMID- 1760107 TI - Methylprednisolone does not protect the lung from inhalation injury. AB - Most clinical studies suggest that corticosteroids are contraindicated in the treatment of acute smoke inhalation. However, they are still used in critical situations with the hope that they might reverse the acute pathophysiological responses to smoke inhalation and thus reduce the severity of the illness or make survival possible. These experiments were done to study the effect of methylprednisolone on the response to smoke inhalation in anaesthetized mongrel dogs. Three experimental protocols were followed: (I) haemodynamics, gas exchange, lung compliance, and lung water were evaluated; (II) pulmonary vascular permeability was assessed by cannulating the afferent tracheobronchial lymphatic and calculating the osmotic reflection coefficient (sigma d) at high lung lymph flows; (III) pulmonary surfactant function was studied using a Wilhelmy balance. Methylprednisolone alone did not alter any measured values compared with those seen in control animals. Treatment with methylprednisolone (30 mg/kg) prior to smoke exposure did not attenuate any of the adverse responses typically seen after smoke inhalation. These data indicate that methylprednisolone does not protect the lung from the acute physiological consequences of inhalation injury. PMID- 1760108 TI - Pain relief in burns: James Laing memorial essay 1990. PMID- 1760109 TI - Pain control in paediatric burns--the use of patient-controlled analgesia. AB - Eleven children received patient-controlled analgesia (PCA) for the management of severe burn pain, their ages ranged from 4.75 to 14 years. Periods of PCA ranged from 2 to 131 days. Three patients developed evidence of tolerance as shown by high dose requirements, but the patients weaned themselves rapidly when pain levels fell. We conclude that PCA provides good quality analgesia to school-age children requiring debridement and grafting for burns. Its use simplified one major aspect of the management of these children. PMID- 1760110 TI - Contact burns due to thermoplastic road paint. AB - Thermoplastic road markings are used at similar temperatures to tar and bitumen and spillage onto skin causes similar contact burns. Most of these occupational burn injuries can be avoided by adherence to the manufacturer's recommendations about the wearing of protective clothing. Management and foremen of contractors using these materials need to ensure that their workers comply with safe procedures and wear the specified protective clothing. PMID- 1760111 TI - An analysis of mortality in patients with burns covering 40 per cent BSA or more: a retrospective review covering 24 years (1964-88). AB - The charts of patients with burns covering more than 40 per cent of the body surface area (BSA) who were admitted to the Burn Unit of the Soroka Medical Center, Beersheva, Israel, between the years 1964 and 1988 were reviewed for mortality rate and causes of deaths. The factors affecting survival are reviewed and analysed. PMID- 1760112 TI - Audit of thermally injured children under 5 years of age. AB - One-third of all admissions to the Wessex Regional Burns Unit (WRBU) are children under 5 years of age. These patients constitute a disproportionately large part of the workload in terms of nursing and medical care. A review of children admitted to the WRBU over a 5-year period was undertaken. Information was stored in a computer database (dBASE-IV) to simplify data analysis and to develop a system of data collection which can be used for audit. Eighty-one per cent of injuries were due to scalds. The mean burn surface area (BSA) was 8 per cent, and 78 per cent of injuries were smaller than 10 per cent BSA. Skin grafting was required in 44 per cent of patients. The mean time to operation was 13 days after injury. Significant hypertrophic scarring occurred in 60 per cent of patients and 12 per cent of patients were readmitted for further surgical procedures. There was one death. In an extension to the main database, associations between clinical and physiological observations and morbidity were sought. The data suggest that behavioural changes, 'shock', profound lymphocytopenia and pyrexia greater than 39.5 degrees C should be treated as strongly suggestive of the development of complications in the early stages after injury. PMID- 1760113 TI - High-tension electrical-arc-induced thermal burns caused by railway overhead cables. AB - Eleven patients with high-tension electrical-arc-induced thermal burns due to railway overhead cables were treated at the Bratislava Burn Department during a relatively short period of 18 months. All the injuries occurred by the same mechanism, that is persons climbing on top of railway carriages and approaching the 25,000 V a.c. overhead cables. All the burns were the result of an electrical arc passing externally to the body, with subsequent ignition of the victim's clothes. The cutaneous burns, ranging from 24 to 79 per cent of the BSA, were mostly deep partial to full skin thickness injuries. One patient died on day 5 postburn, the other survived. In spite of high-tension aetiology, no true electrical injuries appear to have occurred and no amputations were necessary. The pathophysiology and possible preventive measures are discussed. It must be stressed that arcing can be induced by an earthed object approaching, but not touching, a cable carrying a high voltage. PMID- 1760114 TI - 'Is all that's blistered burned?' ... A case of kerosene contact burns. AB - A case of chemical burns following prolonged exposure to kerosene in the home is presented. The appearance are discussed together with the possible systemic effects which have been reported. Early treatment to remove the agent followed by observation and dressing in a burns unit is recommended. PMID- 1760115 TI - The prevention of hot tap water burns--a study of electric immersion heater safety. AB - A household survey conducted in 1986 as part of a study into the prevention of hot tap water burns found that 50 per cent of the immersion heater installations visited produced hot water at temperatures of 60 degrees C or greater. The Electricity Research and Development Centre has carried out a new detailed survey of over 200 electric immersion heater installations to ascertain the effectiveness of thermostats in controlling hot water temperatures. This survey found that immersion heater thermostats were effective and reliable devices, but it was disturbing to record the 71 per cent of the thermostats inspected were set at temperatures greater than 65 degrees C. Hot water temperature measurements showed that only 20 per cent of the homes had hot water with a temperature greater than 65 degrees C at the tap. One possible reason for this may have been the use of hot water by the residents before the temperature measurements were made because, while conducting the survey, it was not possible to have the immersion heater switched on in every apartment due to the time switching arrangements. For the age group surveyed, with an average age of 72 years, the provision of a device to indicate the remaining hot water in a storage cylinder was thought to be helpful but more than half the respondents indicated that they did not want new kinds of remote temperature control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760116 TI - Bilateral visual loss after severe burns in a child. AB - A girl who sustained severe burns was admitted to the hospital 16 h postburn. The patient developed sudden visual loss on day 15 postburn. She responded to treatment with significant return of visual acuity by 5 weeks after injury at the time of discharge from hospital. PMID- 1760117 TI - Parascapular fasciocutaneous flap for covering an above-elbow amputation stump. AB - The successful use of a parascapular fasciocutaneous flap to cover an above-elbow amputation stump with exposed bone is described. Better stability of the stump to pressure (or manipulations), a relatively early one-stage surgical procedure and diminished possibility of later contracture leads to a better long-term outcome. PMID- 1760118 TI - Rupture of the heart in a burn patient: a case report of free wall rupture of the left ventricle. AB - A 63-year-old male was burned when in a state of alcoholic intoxication, he fell head first into a bathtub filled with hot water and received burns covering 40 per cent BSA. Despite surgical wound debridement, a severe sepsis continued and a sudden cardiac arrest occurred. Autopsy revealed a large volume of blood in the pericardial space. The heart was ruptured through a myocardial abscess in the posterior wall of the left ventricle. The principle cause of his death was attributed to acute cardiac tamponade following cardiac rupture through a myocardial abscess. PMID- 1760119 TI - Silver sulphadiazine-induced haemolytic anaemia in a glucose-6-phosphate dehydrogenase-deficient burn patient. AB - A 20-year-old soldier sustained 35 per cent body surface area burns by open flames. He was treated with topical application of 1 per cent silver sulphadiazine (SSD) twice daily. Four days postburn he developed acute haemolytic anaemia. Withdrawal of SSD was followed by complete recovery. A glucose-6 phosphate dehydrogenase (G6PD) deficiency was proven by pathological Motulski tests. Although the hazards of SSD are well indicated by the manufacturers, there appear to be no written reports of haemolysis induced by this drug in G6PD deficient patients. PMID- 1760120 TI - Natural history of 'deep dermal' burns in domestic pigs. PMID- 1760121 TI - Standards of care for hospice patients with pressure ulcers. AB - Pressure ulcers are a major concern of hospice nurses. A recent survey of hospice agencies in an area of the southwest indicated a lack of specific standards of care for patients with pressure ulcers and no systematic method to identify patients at risk. Standards of care were subsequently developed to identify patients at risk and to manage pressure ulcers of hospice patients. PMID- 1760122 TI - Assessment of epithelial thickness by ultrasonic imaging. AB - Moisturizing creams and lotions are an important aspect of preventing pressure ulcers. This study reports the increased thickening of the epithelium on 11 subjects who used a moisturizing cream (treatment) for 20 days. The thickening of the epithelium was measured before use of the moisturizing cream, on day 1, day 8, and day 20 of the treatment, and 12 days after the treatment. The ultrasound measurements were similar before the treatment and 12 days post treatment; the measurements increased for the days of treatment. Current research would lead us to believe that short-term increase in epithelial thickness as produced by a moisturizer is a result of increased water content. Ultrasound imaging may be the new standard for comparing the effects of moisturing products. PMID- 1760123 TI - Silicone injection management of diabetic foot ulcers: a possible model for prevention of pressure ulcers. AB - Long-term clinical and histologic findings with injectable fluid silicone to reduce mechanical forces over plantar skin are described. The fluid induces a relatively stable soft tissue prosthesis between skin and bone, reducing the frequency of insensitive ulcer recurrence in the foot. On the basis of these favorable findings, studies are warranted to determine the fluid's efficacy in prevention of pressure ulcers. PMID- 1760124 TI - Comparisons of heel pressure-reducing devices. PMID- 1760125 TI - Prevention of pressure ulcers in elderly nursing home residents: are special support surfaces the answer? AB - This article describes a research study that compared the effectiveness of two pressure-reducing devices in a group of elderly nursing home residents. The results obtained revealed no significant differences between the two devices--an air-filled overlay and a gel mattress--in terms of pressure ulcer incidence, severity, and healing. Several factors contributed to these results and illustrate the problems encountered when preventing pressure ulcer development in a group of elderly, debilitated nursing home residents. These factors include ease of use of the pressure-reducing device, caregiver and facility characteristics, and critical patient variables. Until these variables are addressed, it is impossible for any device to be effective in preventing pressure ulcer development in nursing homes. PMID- 1760126 TI - Outcomes and critical thinking. PMID- 1760127 TI - Biosensors for the determination of drug substances. AB - A review of the use of biosensors for the determination of drug substances is presented. Although primary emphasis is placed on drugs of abuse, for example, cocaine, heroine, and morphine, other pharmaceutically important drugs, such as theophylline, Inderal, codeine, lidocaine, and the phenothiazines, are also discussed. Applications in both the liquid phase and the gas phase are presented. PMID- 1760128 TI - Immobilization of perfluoroalkylated enzymes in a biologically active state onto Perflex support. AB - Perflex has been introduced by E. I. du Pont de Nemours and Co., Inc., as a new fluorocarbon-based technology for protein immobilization. Due to the hydrophobic character of the support, however, significant loss of enzymatic activity may occur upon immobilization of certain enzymes, which appears to be due to a large conformational change of the protein ("inversion"). Pretreatment of the Perflex support with a neutral fluorosurfactant lessened the surface hydrophobicity, thus decreasing the hydrophobic interaction between the support and the protein. Modification of enzymes with a high number of fluorocarbon residues, which forms a hydrophobic "envelope" around the protein, also appears to prevent enzyme inactivation upon immobilization on Perflex support. Moreover, preactivation of the support with either perfluorooctylpropylisocyanate or reactive poly(fluoroalkyl) sugar reagents greatly improves the enzyme particle activity by increasing the amount of immobilized enzyme. Fluorosurfactant treatment of the support activated with perfluorooctylpropylisocyanate improves the retention of activity for sensitive enzymes such as alpha-chymotrypsin and increases the wetability and ease of handling of the Perflex particles. PMID- 1760129 TI - Cell-culturing characteristics of newly developed PHEMA microcarriers: their use with BHK21 cells. AB - Baby hamster kidney (BHK) fibroblasts, as model cells, have been proliferated on acrylic based microcarriers. Microcarriers were prepared by a novel suspension polymerization of acrylic monomers. Hydroxyethyl methacrylate was the basic monomer. Ethylene glycol dimethacrylate was used as the cross-linker. A hydrophobic comonomer, namely, methyl methacrylate, was included in order to adjust the hydrophilicity of the resultant matrix. An acrylic comonomer with positively charged tertiary amine groups, i.e., dimethylaminoethyl methacrylate, was also added in order to optimize the surface charge of the carriers. The adhesion, spreading, and growth characteristics of BHK cells on these novel beads were studied either in stationary or in submerged culture conditions. The results demonstrate that the cell attachment and growth can be controlled by changing the degree of charge and the hydrophilicity of the poly(hydroxyethyl methacrylate) matrix. PMID- 1760130 TI - Kinetically controlled synthesis of dipeptides using ficin as biocatalyst. AB - The application of the sulfhydryl protease ficin as biocatalyst is proposed as a novel method for enzyme-catalyzed synthesis of dipeptides. The negligible peptidase but considerable esterase activity at alkaline pH facilitated the kinetically controlled formation of peptide bonds by coupling the ester substrates Z-Ala-OMe and Z-Gly-OMe with L-alanine, D-alanine, L-glutamine, D glutamine and L-Cys(acetamidomethyl) respectively. The reaction is accomplished without the occurrence of secondary peptide hydrolysis. Under optimum reaction conditions (pH 9.2, high ratio nucleophile/carboxyl component, 4.8% ethanol, 40 degrees C), the peptide yields ranged from 5 to 91%, depending on the structure of the amino and/or carboxyl component. No racemization was observed in the enzymatic reaction. Application of short-chain peptides has been advocated recently in clinical nutrition. Ficin-catalyzed peptide synthesis might be an attractive biotechnological approach for the synthesis of suitable dipeptides in this respect. PMID- 1760131 TI - Mutual recognition between polymerized liposomes. III. Association processes between avidin and biotin on polymerized liposome surfaces. AB - Association processes between avidin and biotin in various liposome systems were studied. By incorporating biotin onto the polymerized liposome surface, association processes with free avidin were largely decelerated. When the number of binding sites on the liposome surface was taken into account, the corrected association rate constant was 4.3% of the theoretical value for binary collision. The association rate constant between avidin- and biotin-carrying polymerized liposomes was much smaller than those for both the free avidin-free biotin system and the free avidin/biotin-liposome system, probably due to the repulsive hydration phenomenon. The results are discussed both in terms of our understanding of cell-cell recognition phenomena and for the development of drug delivery systems. PMID- 1760132 TI - Thermostabilization of carboxypeptidase A by interaction with its monoclonal antibodies. AB - The effect of interaction of carboxypeptidase A (CPA) with three monoclonal antibodies, each with a different epitope (CP 10, CP 9, and CP 8), on the heat stabilization of enzymes is described. These monoclonal antibodies bind to CPA with a relatively high binding constant (approximately 10(8) M-1) and do not affect its catalytic properties. Intact carboxypeptidase A lost more than 95 and 90% of its esterase and peptidase activities within 120 min at 50 degrees C. The monoclonal antibodies increased the thermal stability of the enzyme by 90 and 60%, as compared with the peptidase and esterase initial activities, respectively. Binding of these monoclonal antibodies, alone or in pairs, to the enzyme epitopes that are supposedly involved in heat denaturation of CPA result in stabilization of the conformation of the enzyme. The effect of thermostabilization by monoclonal antibodies was more pronounced with respect to peptidase activity than to esterase activity, indicating that these activities follow different reaction mechanisms. Since properly selected monoclonal antibodies can be prepared against virtually any enzyme, their immunocomplexation may provide a general and convenient method for stabilization of the enzyme conformation to heat denaturation, without affecting the catalytic properties. PMID- 1760133 TI - alpha-Chymotrypsin in plastein synthesis: influence of substrate concentration on enzyme activity. AB - The role of alpha-chymotrypsin in the plastein reaction was studied using a peptic hydrolysate of albumin as substrate. Study of this reaction simultaneously by different methods showed that the plastein reaction is enzyme catalyzed and is highly dependent on environmental conditions. A gel permeation chromatography study of the plastein reaction showed simultaneous increases in the high- and low molecular-weight oligopeptide fractions; a transpeptidation mechanism may be involved in the reaction. A study of the effect of substrate concentration on the plastein reaction catalyzed by alpha-chymotrypsin showed a profile with both hydrolytic and synthetic activities. This effect was also observed when the reaction course was followed by quantification of the free amino groups at different substrate concentrations, showing that a condensation mechanism is responsible for the synthetic activity when the substrate concentration is very high. These results have led us to conclude that the plastein reaction involves a transpeptidation and/or condensation mechanism, which is a function of the substrate concentration. PMID- 1760134 TI - Isolation and fundamental characteristics of a phospholipase B inhibitor from autolyzed Torulaspora delbrueckii. AB - Phospholipase B inhibitor was found in the autolyzate of yeast cells, Torulaspora delbrueckii. The inhibitor was purified to homogeneity by ethanol precipitation, gel filtration with Sephadex G-10, ion-exchange chromatography with DEAE Sephacel, and gel filtration with Asahipak GS-320. On thin-layer chromatography the purified inhibitor was detected with the Hanes-Isherwood reagent, which is used to detect phosphorus. The activity of the inhibitor was not affected by heat treatment at 100 degrees C for 1 h. Heating at 100 degrees C for 1 h in 1 M HCl and 1 M NaOH lowered activity to 76 and 80% of the original values, respectively, but heating at 110 degrees C for 24 h in 6 M HCl completely abolished activity. The inhibitor was highly soluble in water, but practically insoluble in alcohol, acetone, ether, and chloroform. The degree of inhibition of enzyme activity was not proportional to the concentration of inhibitor. The inhibitor inhibited both membrane-bound and water-soluble phospholipase B activity from T. delbrueckii at the same level; however, the inhibitor did not inhibit the activity of phospholipase A2 from snake venom (Naja naja). PMID- 1760135 TI - An automated RNA extraction procedure and application for 16S rRNA sequencing of Leuconostoc amelobiosum. AB - The determination of 16S ribosomal ribonucleic acid (16S rRNA) primary structures by in vitro reverse transcription requires the extraction of rRNA in pure form. Although a number of high reliable techniques have been developed for the purpose most are fairly complex, involving numerous steps and the wasting of large volumes. It describes here a RNA extraction and purification method, suitable for automatic extractors, which consistently yields reasonable amounts of pure total RNA from prokaryotes, free of DNA and RNases. The rRNA from the type strain Leuconostoc amelobiosum was isolated using this procedure. Its 16S rRNA sequence was determined and a comparative analysis with those from all currently described leuconostocs, including several atypical lactobacilli, revealed very high sequence homology with Leuconostoc citreum confirming Leuconostoc amelobiosum is phylogenetically a member of the genus Leuconostoc sensu stricto. PMID- 1760136 TI - [ Taxonomic study of the yeast flora of musts and wines from "Madrid wines"]. AB - The natural yeast flora of musts and wines elaborated in wineries of the three Madrid viticultural areas, has been taxonomically analyzed. Two hundred and seventy yeast strains belonging to eighteen species, have been isolated, and Sacch. cerevisiae strains are the most frequent. The chemical characterization of samples with enological parameters defines the yeast fermentative ecosystem. PMID- 1760137 TI - Increase of hemolysin expression in Escherichia coli by cloned DNA sequences of Serratia marcescens. AB - A genomic library of Sau 3AI-generated Serratia marcescens DNA fragments was constructed in Escherichia coli 5K harbouring plasmid pANN202-312. Two clones capable of increasing the external hemolytic activity of the parental strain were isolated and characterized. The recombinant plasmids purified from these clones (designated pPSF29 and pPSH18) contained approximately 30 and 20 Kb, respectively, of Serratia DNA. Introduction of either plasmid in Escherichia coli caused a marked increase in hemolysin production and a concomitant decrease in cell viability. PMID- 1760138 TI - Distribution of oxidizing bacterial activities and characterization of bioleaching-related microorganisms in a uranium mineral heap. AB - The occurrence and activity of bioleaching-related microorganisms are highest at 0.25 m under the surface of a uranium mineral heap, and decrease at points deeper than 1 m inside the heap. Thiobacillus ferrooxidans, Th. acidophilus, Th. thiooxidans and Leptospirillum ferrooxidans have been found and isolated from different sites inside the heap. Other mesophilic iron- or sulphur-oxidizing bacteria and some moderate thermophile have also been isolated from deep (1 m and 4 m) sites and characterized. Several fungi and some yeasts are present in this bioleaching habitat. PMID- 1760139 TI - Methodology employed for the structure determination of tumour necrosis factor, a case of high non-crystallographic symmetry. AB - The structure of the protein tumour necrosis factor (TNF) was determined from crystals of space group P3(1)21 which contain six copies of the TNF monomer per crystallographic asymmetric unit [Jones, Stuart & Walker (1989). Nature (London), 338, 225-228]. The nature of these crystals (relatively high crystallographic symmetry coupled with multiple copies of the protein in the asymmetric unit) led to some peculiarly challenging problems at several points in the structure determination. In particular, (1) self-rotation function calculations failed to yield clearly interpretable solutions, (2) the analysis of difference Patterson maps for heavy-atom derivatives required the development of a Patterson search program suite GROPAT. The redundancy in the asymmetric unit allowed refinement of poor-quality isomorphous phases at 4 A resolution and phase extension from 4 to 2.9 A resolution using real-space symmetry averaging and solvent flattening in the absence of any isomorphous phase information. Despite further difficulties caused by structural differences between the six independent copies of the monomer the resultant electron density map was of high quality and proved to be easily interpretable. PMID- 1760140 TI - A multisolution method of phase determination by combined maximization of entropy and likelihood. V. The use of likelihood as a discriminator of phase sets produced by the SAYTAN program for a small protein. AB - The use of a likelihood criterion associated with maximum-entropy (ME) extrapolation for selecting phase sets as part of a new multisolution phasing strategy, already applied to solving small crystal structures from single-crystal data [Gilmore, Bricogne & Bannister (1990). Acta Cryst. A46, 297-308] and X-ray powder diffraction data [Gilmore, Henderson & Bricogne (1991). Acta Cryst. A47, 830-841], has been tested on the small protein avian pancreatic polypeptide (APP) with 301 non-H atoms in the asymmetric unit in space group C2. A collection of 50 phase sets for APP were provided by Woolfson & Yao. They had been generated from random starting phases by the SAYTAN procedure [Woolfson & Yao (1990). Acta Cryst. A46, 409-413] using data to a resolution of 0.98 A. Six of these had an unweighted mean absolute phase error, mean value of magnitude of delta phi, of less than 50 degrees, the remainder having phase errors of 60 degrees or more. However, none of the conventional figures of merit were able to identify these preferred sets. Each phase set was subjected to our standard procedure of entropy maximization and of evaluation of the log-likelihood gain resulting from the associated ME extrapolation. With only a small subset of data (to 2 A resolution), the likelihood criterion identified unambiguously the phase sets with mean value of magnitude of delta phi less than 50 degrees. In contrast, conventional figures of merit showed no such ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760141 TI - In vitro studies on the microbicidal effectiveness of a xenon-based ultraviolet light device for continuous ambulatory peritoneal dialysis connections. AB - Mercury vapor sourced ultraviolet light has been used for several years to disinfect connections that are integral to peritoneal dialysis solution delivery systems. This in vitro study evaluated the suitability of xenon flash sourced ultraviolet light as an effective alternative disinfecting agent. Candida albicans was determined to be at least four times more resistant than Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus mitis, and Pseudomonas aeruginosa to ultraviolet radiation generated by both mercury vapor and xenon flash devices. Both ultraviolet devices effectively disinfected transfer set spikes that were inoculated intraluminally with each of these five test microorganisms suspended in a pool of patient dialysis effluent. However, ultraviolet (254 nm) absorbance values of dialysis effluent was found to vary greatly between patients, with the most ultraviolet-opaque effluent significantly reducing the microbicidal effectiveness of the mercury vapor, but not the xenon flash system. PMID- 1760142 TI - Hypoventilation in a dialysis patient with severe metabolic alkalosis: treatment by hemodialysis. AB - A patient with end-stage renal disease (ESRD) developed metabolic alkalosis and alkalemia from protracted vomiting. As a result of the absence of the alkali excretory capacity in this patient with ESRD, the alkaline load accumulated rapidly. Once the amount of acid lost from vomiting exceeded the amount of acid gained from metabolism, alkalemia supervened. The initial arterial blood gas on room air revealed hypercarbia, hypoxia and alkalemia. Her serum bicarbonate was greater than 50 mEq/l. Compensatory hypoventilation occurred. In this report, the extent of compensatory hypoventilation in the setting of metabolic alkalosis in patients treated for ESRD and therapeutic approaches to this problem will be discussed. Treatment was aimed at correcting the primary disorder, namely metabolic alkalosis. Conventional bicarbonate dialysis was shown to be effective in improving acid-base homeostasis in this patient. PMID- 1760143 TI - Diagnostic approaches to AB-amyloidosis. AB - AB-amyloidosis, characterized by the presence of beta 2-microglobulin in the amyloid fibrils, has become an important complication of long-term renal replacement therapy. Due to the mainly musculoskeletal manifestation of the disease, standard approaches to obtain the diagnosis of amyloidosis, such as rectal biopsy or fat aspiration, often yield negative results. Currently, definitive diagnosis relies on biopsies, usually of synovial membranes or bone cystic radiolucencies. The serum level of beta 2-microglobulin, though markedly elevated, does not distinguish between patients with and without amyloid deposition. Measurements of altered, circulating beta 2-microglobulin species have not yet been evaluated in this regard. Recently, two radiopharmaceuticals, namely radiolabelled serum amyloid P component and radiolabelled beta 2 microglobulin, have been shown to be able to detect amyloid deposits in vivo in a noninvasive manner. At least in the case of labelled beta 2-microglobulin it enables the specific detection of clinically and radiologically unrecognizable AB amyloid deposits. These tests therefore may have the potential to alleviate the need for biopsy confirmation in the diagnostic workup of a suspected AB amyloidosis. PMID- 1760144 TI - Bronchial reactivity in patients undergoing long-term haemodialysis for chronic renal failure. AB - Trapping of neutrophils within the lung occurs in patients undergoing haemodialysis and is also a possible mechanism in the pathogenesis of bronchial hyper-responsiveness. Falls in peak expiratory flow rate occur in most dialysis patients, and some develop overt asthmatic symptoms. To see whether these changes in airway function are secondary to increases in bronchial reactivity during haemodialysis, we therefore performed histamine challenge testing in 6 non asthmatic patients before and after haemodialysis. No change in reactivity was observed, suggesting that haemodialysis does not commonly result in bronchial hyper-reactivity in non-asthmatic individuals. PMID- 1760145 TI - Measurement of backfiltration rates during hemodialysis with highly permeable membranes. AB - A method for determining local transmembrane fluid movement in a commercial hemodialyzer at low dialysate flow rates by measuring changes along the dialyzer length in the local concentration of a marker macromolecule added to the dialysis solution has been developed. The method was evaluated in vitro at zero net ultrafiltration using dialyzers containing polysulfone (n = 4) and cuprophane (n = 3) membranes. The local concentration of the marker macromolecule along the dialyzer length was higher than the input dialysate concentration only during experiments with dialyzers containing polysulfone membranes. These observations provide direct empirical evidence that fluid movement in the dialysate to blood direction, i.e., backfiltration, occurs during hemodialysis with this highly permeable membrane. Net rates of backfiltration for the dialyzer containing polysulfone membrane were also calculated from changes in the local concentration of the marker macromolecule and mass balance considerations. The calculated backfiltration rates increased with increasing blood flow rate and trended upward with increasing dialysate flow rate. The described methodology provides a novel approach for the further characterization of fluid and solute transport during hemodialysis with highly permeable membranes. PMID- 1760146 TI - Plasmapheresis in conjunction with the dextran sulfate cellulose column for hypertriglyceridemic patient: a comparison with familial hypercholesterolemia. AB - For assessment of the usefulness of a dextran sulfate cellulose (DSC) column in the conduct of plasmapheresis (DSC lipoprotein adsorption, DSC-LA) for patients with hypertriglyceridemia on hemodialysis, a study was conducted to determine whether the adsorption of lipoproteins on a column varies in response to a variation in the lipoprotein composition. A patient with type V hyperlipoproteinemia on hemodialysis, a patient with type IIa homozygous, and a patient with type IIa heterozygous familial hypercholesterolemia were used in this study. In all patients, apolipoprotein B- and E-containing lipoproteins were removed preferentially by a DSC column. Following DSC-LA, abdominal pain before DSC-LA in a patient with type V hyperlipoproteinemia subsided, and regression of tuberous and tendinous xanthomas was induced in familial hypercholesterolemia. In cases of hyperlipoproteinemia, this column thus appears to exert a therapeutic effect regardless of the type of disease. PMID- 1760147 TI - In vitro study of the transfer of cytokine-inducing substances across selected high-flux hemodialysis membranes. AB - The in vitro transfer of cytokine-inducing substances (CIS) across cellulose triacetate and polyacrylonitrile hollow-fiber high-flux hemodialyzers was studied using culture filtrates of gram-negative bacteria isolated from hemodialysis center environments. With Enterobacter cloacae, no transfer of CIS was seen despite the potent cytokine inducibility and endotoxin content of the challenge solution. In contrast, interleukins 1 and 6 and tumor necrosis factor inducing substances did penetrate both dialyzer types challenged with Pseudomonas aeruginosa culture filtrates containing a high endotoxin content. Transfer was not seen, however, upon dilution of the challenge solution to lower, yet clinically very high levels of endotoxin. These results show that, in vitro, the transfer of CIS across high-flux membranes is critically dependent upon the quality and the quantity of the challenge material employed. PMID- 1760148 TI - Colorimetric assay of methyldopa bulk drug and tablets as its Fe(III) complex. AB - A new colorimetric method for the determination of methyldopa is described. The method is based on the reaction of methyldopa with ferric chloride in the pH range of 3.0-3.5 and producing a water soluble (1:2) brown complex with maximum absorbance at 423 nm. The conditional stability constant of the complex at the optimum pH 3.0 and ionic strength 0.4 M, is found to be 10(7.5). Beer's low is obeyed up to 6 mmol/l methyldopa concentration. The RSD of the method is 0.708 1.226%. The proposed method was found to be suitable for the accurate and reproducible analysis of methyldopa bulk drug and tablets which is pointed by high recovery values 99.20-99.79%. PMID- 1760149 TI - In vitro activity of phenyl-O,N,N-azoxycyanide towards Candida spp. and Torulopsis spp. AB - Antifungal activity in vitro of phenyl-0,N,N-azoxycyanide has been tested against some strains of Candida spp. and Torulopsis spp. freshly isolated from humans. The results indicate good activity versus all yeasts tested. These data suggest that the azoxycyanide function could be used to obtain derivatives with potent anticandidal action, if conveniently vehicled by lypophylic compounds. PMID- 1760150 TI - Computation of release kinetics of isoniazid microcapsules. AB - Isoniazid is a drug of choice for intermittent chemotherapy of tuberculosis. It has been microencapsulated by emulsification followed by solvent evaporation technique using Eudragit RS 100 as polymer where free flowing, spherical and discrete microcapsules have been formed as obtained by SEM. The drug release data have been computed in the light of various kinetic models, where it is found that the matrix release mechanism predominates over the first and zero order mechanism for isoniazid microcapsules, even if the sizes and drug polymer ratio of the microcapsules were varied. PMID- 1760151 TI - Biotransformation kinetic of binifibrate and identification of its metabolites. AB - The metabolism of binifibrate was studied in 10,000 g supernatant fractions from rat liver. Binifibrate was found to be completely biotransformed into clofibric acid and nicotinic acid at 60 min from the start of incubation through a series of intermediate products among which glycerol dinicotinate was identified. The biotransformation constant of binifibrate into its different metabolites proved to be 0.11 +/- 0.025 min-1. The formation of clofibric acid follows a first-order kinetic process characterized by its corresponding rate constant (kc), proving to be 0.043 +/- 0.017 min-1. The amount of clofibrate was 0.78 +/- 0.16 mumol/ml, showing that it is not biotransformed later in the incubation mixture. The formation constant of nicotinic acid (kn) was 0.067 +/- 0.020 min-1 and the amount of substance contained in the incubation mixture (0.94 +/- 0.25 mumol/ml shows that it is later biotransformed in the incubation mixture through the previously described metabolic processes. PMID- 1760152 TI - [Biotechnology and diagnosis: the molecular DNA probe]. PMID- 1760153 TI - New process for the anaerobic treatment of industrial wastes with high organic content. PMID- 1760154 TI - Characterization of the integral membrane polypeptides of rat liver peroxisomes isolated from untreated and clofibrate-treated rats. AB - We have characterized the integral membrane polypeptides of liver peroxisomes from untreated rats and rats treated with clofibrate, a peroxisome proliferator. Membranes, prepared by treatment of purified peroxisomes with sodium carbonate, were used to raise an antiserum in rabbits. Immunoblot analysis demonstrated the reaction of this antiserum with six peroxisomal integral membrane polypeptides (molecular masses, 140, 69, 50, 36, 22, and 15 kDa). Treatment of rats with the hypolipidemic drug clofibrate caused a 4- to 10-fold induction in the 69-kDa integral membrane polypeptide, while the other integral membrane polypeptides remained unchanged or varied to a lesser extent. The anti-peroxisomal membrane serum reacted with two integral membrane polypeptides of the endoplasmic reticulum which co-migrated with the 50- and 36-kDa integral membrane polypeptides of the peroxisome. Biochemical and immunoblot analyses indicated that these integral membrane polypeptides were co-localized to peroxisomes and endoplasmic reticulum. Immunoprecipitation of in vitro translation products of RNA isolated from free and membrane-bound polysomes indicated that the 22-, 36-, and 69-kDa integral membrane polypeptides were synthesized on free polysomes, while the 50-kDa integral membrane polypeptide was predominantly synthesized on membrane-bound polysomes. The predominant synthesis of the 50-kDa integral membrane polypeptide on membrane-bound polysomes raises interesting possibilities concerning its biosynthesis. PMID- 1760155 TI - In vitro formation of retinoic acid from retinal in rat liver. AB - Enzymatic conversion of retinal to retinoic acid in rat liver cytosol was detected using a rapid and sensitive assay based on high pressure liquid chromatography (HPLC). This retinal oxidase assay system did not require extraction steps or any other manipulation of the sample mixture once the sample vial was sealed for incubation. The product (retinoic acid) and the reactant (retinal) were separated by HPLC in 14.0 min with a sensitivity of 15 and 40 pmol per injection for retinoic acid and retinal, respectively. Enzymatic activity was observed to be linear with protein concentration (0-2.4 mg/mL) and time (0-30 min) and displayed a broad pH maximum of 7.7-9.7. The enzyme exhibited Michaelis Menten single-substrate kinetics with an apparent Km of 0.25 mM. The average specific activity in nine normal rats was 35.6 +/- 3.3 nmol retinoic acid formed/h per mg protein. Incubation of the enzyme with zinc did not affect the rate of retinoic acid synthesis. Dithiothreitol inhibited the reaction. Both NAD and NADH stimulated retinoic acid formation. Formation of retinol was also observed when these pyridine nucleotides were added to the reaction mixture, indicating the presence of retinal reductase activity. The results of kinetic studies suggest that NADH may act indirectly to stimulate retinoic acid formation. PMID- 1760156 TI - Further purification and characterization of newly synthesized anionic glycoconjugates secreted by cultured UMR-106 cells: evidence that the major anionic glycoconjugate secreted by these cells is similar to bone sialoprotein II. AB - Following incubation of UMR-106 cells for 48 h in the presence of [3H]glucosamine and [35S]sulfate, the newly synthesized anionic glycoconjugates were isolated from the culture medium by cetylpyridinium chloride/ethanol precipitation and further separated by DEAE-Sephacel chromatography into two radiolabelled fractions, a major component, UM I, and a minor component, UM II. UM I appeared to be homogeneous as shown by Sepharose CL-4B chromatography under dissociative conditions, and SDS-polyacrylamide gel electrophoresis. It showed a molecular mass of approximately 93 kDa on 4-15% gels. UM I was partially degraded by brief treatment with trypsin, releasing a small, terminal peptide that contained 47.6% of 35S but no 3H. Treatment of UM I with neuraminidase and 0.1 N H2SO4 (1 h at 80 degrees C), respectively, released 27% 3H and 38.4% 3H plus 41% 35S, suggesting the presence of a significant number of sialic acid residues, as shown by Sephadex G-50 chromatography of the digests. Amino acid analysis showed that the UM I glycoconjugate was rich in acidic amino acids (12.6% aspartic acid and 21.2% glutamic acid residues) and its N-terminal sequence was Phe-Ser-Met-Lys-Asn-Phe-, which is identical to the published N-terminal amino acid sequence of rat bone sialoprotein II. Keratanase treatment of UM I released 26% of the incorporated radioactivity, suggesting the presence of keratan sulfate chains. UM II contained a chondroitinase ABC-sensitive proteoglycan. PMID- 1760157 TI - Isolation, ultrastructure, and partial characterization of collagen from the perineurium of the Florida lobster, Panulirus argus. AB - Highly concentrated extracellular filaments in the perineurium of the Florida spiny lobster, Panulirus argus, were isolated using ultracentrifugation and linear sucrose gradients. The pellet obtained was highly enriched for the filaments as observed by transmission electron microscopy. Fibril diameter and axial periodicity measurements were obtained from filaments positively and negatively stained with uranyl acetate. A period between 14.0 and 25.0 nm and an average fibril diameter of 15.0 nm were observed. The filaments proved resistant to solubilization by most conventional agents and by several collagenases. NaOH (0.1 M at 100 degrees C) safely dissolved the filaments for measurements of protein content by the Lowry method and carbohydrate content with anthrone reagent. These tests revealed a protein content of approximately 84% and a high carbohydrate content of approximately 15%. Polyacrylamide electrophoresis of an acid-pepsin filament extract revealed a highly concentrated band (approximately 100,000) corresponding to the alpha-1 and alpha-2 bands of vertebrate type I collagen. Wide angle X-ray diffraction yielded meridional reflections that confirmed the filaments as collagen when compared with mammalian collagen X-ray diffraction. The amino acid composition was determined with a computer-assisted Beckman amino acid analyzer, which showed a glycine content of 279 residues/1000. Hydroxylysine and hydroxyproline were present in lower concentrations than expected. PMID- 1760158 TI - Purification and the effect of peptide N-glycosidase F on lysosomal membrane bound glucocerebrosidase from human cultured fibroblasts. AB - Glucocerebrosidase was purified from human cultured dermal fibroblasts more than 2200-fold to apparent homogeneity using high performance Alkyl-Superose HR 5/5 hydrophobic interaction and Bio-Sil TSK-250 gel permeation column chromatography. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis and protein staining of the catalytically active and concentrated enzyme fractions from the gel permeation columns revealed the presence of one band of Mr 64,000. The glucocerebrosidase preparation purified to homogeneity was digested with peptide N-glycosidase F that cleaves N-linked oligosaccharide structures from glycoproteins. The molecular weight of glucocerebrosidase after digestion with peptide N-glycosidase F was reduced to Mr 57,000, suggesting that the mature enzyme is a glycoprotein and that N-linked oligosaccharide constitutes a minimum of about 10% of the total molecular weight of the polypeptide. These findings are compatible with the hypothesis that glucocerebrosidase was initially synthesized as a precursor polypeptide which was subsequently glycosylated to become the mature enzyme. PMID- 1760159 TI - Folylpolyglutamate synthetase from beef liver: purification and some properties. AB - The polypeptide chain of folylpolyglutamate synthetase from beef liver has been isolated and partially characterized. This polypeptide has an apparent molecular weight of 73,000. Its amino-terminal residue is blocked. Amino acid analysis agrees with the hydrophobic properties and the pI (6.0) of this cytosolic enzyme. Polyclonal antibodies to the denatured enzyme have been prepared. PMID- 1760160 TI - Isolation and partial characterization of a soluble mucin in human pancreatic juice. AB - Morphological and histochemical abnormalities in pancreatic mucin occur in many pancreatic disorders. However, the composition of pancreatic mucin is poorly understood. Purified mucin was isolated from pure pancreatic juice by sequential chromatography on Sepharose CL-2B and CL-4B followed by CsCl density gradient ultracentrifugation. The mucin preparation consists of 24% protein and 73% carbohydrate. Reduction of the macromolecule (greater than 2 x 10(6)) by mercaptoethanol resulted in the formation of subunits of molecular weight 500,000 and released several small molecular weight proteins, including a glycoprotein of an average molecular weight of 116,000. Cellulose acetate electrophoresis separated the mucin into three species of different staining properties for periodic acid-Schiff reagent and Alcian blue, suggesting the presence of microheterogeneity with respect to sulphation and sialation. Threonine, serine, and proline composed 48% of the total amino acids, while the oligosaccharide moiety contained N-acetylglucosamine, N-acetylgalactosamine, fucose, galactose, sialic acid, and sulphate. We also detected the presence of C16:0 and C18:0 fatty acids which were probably noncovalently bound to the pancreatic mucin. PMID- 1760161 TI - Analysis of the activation of poly(ADP-ribose) polymerase by various types of DNA. AB - In this work, we examined the activation of poly(ADP-ribose) polymerase by various types of DNA. We have found that the best activator for poly(ADP-ribose) polymerase is an octanucleotide. However, the use of a defined activated DNA is also suitable. PMID- 1760162 TI - Frequency of anesthetic cardiac arrest in infants: effect of pediatric anesthesiologists. PMID- 1760163 TI - Frequency of anesthetic cardiac arrests in infants: effect of pediatric anesthesiologists. AB - STUDY OBJECTIVE: To determine whether the presence of pediatric anesthesiologists decreases the frequency of anesthetic-related cardiac arrests in infants (children who are 1 year of age or younger). DESIGN: A comparative retrospective study of anesthetics and cardiac arrests during a 7-year period. SETTING: The main operating room (OR) suite of a large university hospital. PATIENTS: All patients age 1 year or less undergoing surgical anesthesia from July 1983 through March 1990. INTERVENTIONS: Computerized anesthetic and operative patients records were queried for patient age, ASA physical status, body weight, surgical procedure, intraoperative complications, and the identity of the attending anesthesiologist. In each case, it was determined whether a pediatric anesthesiologist was in attendance and whether a cardiac arrest due to anesthesia occurred. Pediatric anesthesiologists were identified as those with pediatric fellowship training or the equivalent. The study population was divided into two groups: (1) the pediatric anesthesiologist group, with 2,310 patients whose anesthetics were supervised by pediatric anesthesiologists; (2) the nonpediatric anesthesiologist group, with 2,033 patients. MEASUREMENTS AND MAIN RESULTS: Mean age and weight were comparable in the two groups, and the distribution of physical status did not differ. No anesthesia-related cardiac arrests occurred in the pediatric anesthesiologist group; four anesthetic cardiac arrests occurred in the nonpediatric anesthesiologist group, for a frequency of 19.7 per 10,000 anesthetics. This difference between provider groups is significant (Fisher's exact probability test, p = 0.048). CONCLUSIONS: The results suggest that the use of pediatric anesthesiologists for all infants 1 year of age or younger might decrease anesthetic morbidity in this age-group. PMID- 1760164 TI - Comparison of train-of-four and posttetanic response as guides for endotracheal intubation in children. AB - STUDY OBJECTIVE: To evaluate and compare the predictive values of the absence of train-of-four (TOF) or posttetanic response as guides for endotracheal intubation in children. DESIGN: Prospective controlled study in children. SETTING: Induction of anesthesia and endotracheal intubation at a university-affiliated hospital. PATIENTS: Thirty pediatric patients age 1 to 10 years, ASA physical status I, who were undergoing elective surgery were divided into two equal groups. INTERVENTIONS: Anesthesia was induced with halothane and maintained at 1% inspired concentration. Fifteen children were stimulated with the TOF (2 Hz for 2 seconds) technique and 15 with the twitch-tetanus-twitch sequence. All the patients received atracurium 0.4 mg/kg. Upon abolishment of the TOF or tetanus twitch sequence, endotracheal intubation was performed and the conditions for intubation were evaluated. MEASUREMENTS AND MAIN RESULTS: In the group of patients stimulated by the TOF technique, the neuromuscular response was ablated in 1.7 +/- 0.1 minutes, a significantly shorter time than in those stimulated by the tetanus-twitch sequence (4.0 +/- 0.4 minutes; p less than 0.0001). Conditions for intubation did not differ between the two groups. CONCLUSIONS: Good intubating conditions can generally be counted on when the TOF has disappeared; additional waiting for the disappearance of posttetanic response is unnecessary. The observation that the disappearance of the tetanus-twitch sequence is a good indicator of deep neuromuscular blockade during recovery from atracurium in children cannot be extrapolated to the induction period. PMID- 1760165 TI - Nasal continuous positive airway pressure: an alternative method for respiratory assistance. AB - STUDY OBJECTIVE: To examine the efficacy of a nasal continuous positive airway pressure (CPAP) system for respiratory support in patients who have respiratory insufficiency but are able to maintain spontaneous breathing without hypercapnia, respiratory acidosis, or deteriorated mental status. DESIGN: Prospective study. SETTING: Medical and surgical patients admitted to the intensive care unit (ICU) at the Hillel Yaffe Medical Center. PATIENTS: Nineteen patients with acute respiratory insufficiency and intact mental status who were able to maintain spontaneous breathing without hypercapnia or respiratory acidosis. Additional entry criteria were as follows: arterial oxygen tension (PaO2) less than 65 mmHg on inspired oxygen tension (FIO2) greater than or equal to 0.45, PaO2/FIO2 less than 150, respiratory rate greater than 35 breaths/minute, and inability to tolerate mask CPAP. INTERVENTIONS: Nasal CPAP (10 cmH2O) was applied to patients through two nasopharyngeal airways with an internal diameter (ID) of 8 mm each, inserted in both nostrils. During CPAP application, the patients were requested to breathe through their nose with their mouth closed. Even if they breathed through their open mouth, however, CPAP was maintained despite an observed pressure decrease of 4 cmH2O. MEASUREMENTS AND MAIN RESULTS: All patients showed a constant improvement in arterial blood gases, PaO2/FIO2, and respiratory signs during nasal CPAP of 10 cmH2O. PaO2 increased from 52 +/- 5.3 mmHg to 131 +/- 20 mmHg with CPAP administration (p less than 0.05), while arterial carbon dioxide tension (PaCO2) increased from 32 +/- 2 mmHg to 36 +/- 2 mmHg (p less than 0.05) and respiratory rate decreased from 39 +/- 2.3 breaths/minute to 31 +/- 1.6 breaths/minute (p less than 0.05). CONCLUSIONS: Nasal CPAP (10 cmH2O) is a reliable alternative to support arterial oxygenation in patients with respiratory failure who are alert and vigorous enough to avoid hypercapnia and respiratory acidosis while breathing spontaneously. In addition, since the patients are able to speak and thus are capable of expressing their feelings, the anxiety observed during respiratory support can be reduced. PMID- 1760166 TI - Pulse oximetry from the nasal septum. AB - STUDY OBJECTIVE: To evaluate the accuracy of the nasal septum site for pulse oximetry measurement of arterial oxyhemoglobin saturation (SpO2) in hypothermic patients. DESIGN: Prospective study. SETTING: Operating theater of a public hospital. PATIENTS: Fourteen hypothermic (temperature 34.6 degrees C to 36 degrees C) patients (eight males and six females) undergoing a major surgical abdominal procedure. INTERVENTIONS: Fifty estimations of SpO2 were simultaneously made by a flex sensor probe applied at the nasal septum site and by a finger sensor probe using a pulse oximeter. The results were compared with arterial oxygen saturation (SaO2) as measured by arterial blood gas sampling. MEASUREMENTS AND MAIN RESULTS: In 18% of the estimations, the finger probe produced unmeasurable results. The nasal septum probe did not produce any unmeasurable results (p = 0.0055). In the remaining 41 estimations, a comparison of the measurements from the nasal septum versus the controls showed a mean difference of 0.15 and a limit of agreement of -0.106 to +0.398. A comparison difference of 2.27 and a limit of agreement of 1.986 to 2.551. CONCLUSION: Monitoring SpO2 at the nasal septum site is more reliable than monitoring it at the finger site in hypothermic patients. PMID- 1760167 TI - Effect of preanesthetic intramuscular ranitidine on gastric acidity and volume in children. AB - STUDY OBJECTIVE: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children. DESIGN: Three randomized treatment groups. SETTING: Central operating rooms at a university hospital. PATIENTS: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation. INTERVENTIONS: IM ranitidine 1 mg/kg (n = 15) or 2 mg/kg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient. MEASUREMENTS AND MAIN RESULTS: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mg/kg) than in the controls (8.6 ml; p less than 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p less than 0.05). Dose-dependent plasma ranitidine concentrations were obtained. CONCLUSIONS: Preanesthetic IM ranitidine 1 to 2 mg/kg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premedication for children who have a greater than normal risk of pulmonary aspiration during anesthesia. PMID- 1760168 TI - Weaning with end-tidal CO2 and pulse oximetry. AB - STUDY OBJECTIVE: To determine whether continuous measurement of arterial oxyhemoglobin saturation (SpO2) and end-tidal carbon dioxide (P(ET)CO2) can be used to wean patients safely and efficiently from postoperative mechanical ventilation after cardiac surgery. DESIGN: Prospective study comparing SpO2 and P(ET)CO2 to calculated arterial oxygen saturation (SaO2) and arterial carbon dioxide tension (PaCO2) obtained from blood gas analysis. SETTING: Cardiac surgical intensive care unit at a university-affiliated hospital. PATIENTS: Ten patients requiring elective coronary artery bypass grafting (CABG) were studied in the postoperative period during weaning from mechanical ventilation. INTERVENTIONS: Continuous monitoring of SpO2 and P(ET)CO2 was used to wean patients from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The patients were weaned from mechanical ventilation in an average time of 6.5 +/- 1.5 hours (mean +/- SD). A plot of SaO2 versus SpO2 indicated a high correlation (r = 0.84) with sensitivity (100%) for hypoxemia (SaO2 less than 90%). P(ET)CO2 was a good indicator of PaCO2 (r = 0.76); its sensitivity to detect hypercarbia (PaCO2 less than 45 mmHg) was 95%. The gradient between SpO2 and SaO2 was not significantly affected by the weaning process, but the PaCO2-P(ET)CO2 gradient decreased significantly as the ventilator rate was decreased (p less than 0.001). The weaning process was discontinued on four separate occasions because of metabolic acidosis. Ninety-five percent of arterial blood samples confirmed the weaning recommendations based on the continuous monitoring of SpO2 and P(ET)CO2. CONCLUSIONS: Continuous monitorin of SpO2 and P(ET)CO2 can be used to wean patients safely and effectively after CABG when adjustment of minute ventilation compensates for an increased PaCO2-P(ET)CO2 gradient during controlled ventilation. PMID- 1760169 TI - Anesthetic management of obstructive sleep apnea patients. AB - Presented in an illustrative case report and a review of the anesthetic management of obstructive sleep apnea patients. Preoperative evaluation should include a thorough airway evaluation and a comprehensive cardiovascular and pulmonary evaluation. With polysomnography, identification of the severity of sleep apnea can be idenified. Although sleep centers vary in their definitions, severe obstructive sleep apnea is diagnosed if the patient demonstrates an apnea index greater than 70 and an oxygen (O2) desaturation less than 80% with cardiovascular sequelae. Severe sleep apnea patients are at extreme risk for general anesthesia. These risks should be discussed preoperatively with the patient. Unsupervised preoperative sedation should be avoided because of the extreme sensitivity of these patients to sedatives and airway obstruction. Intraoperative management of the obstructive sleep apnea patient varies depending on the severity of the sleep apnea. Invasive monitoring may be necessary if the patient demonstrates evidence of cardiopulmonary dysfunction. With the assistance of the otolaryngologist, the anesthesiologist can formulate an approach to establishing an airway. Intraoperative opioids and sedatives should be limited. The recovery of the sleep apnea patient is extremely important and is the time when most airway emergencies occur. Extubation of the patient should occur when appropriate surgical personnel and equipment are available in case of an airway emergency. Steroids may be used to decrease the amount of airway swelling. Supplemental O2 should be used in patients who demonstrate desaturation. Opioids and sedatives should be avoided, as should other drugs that have central and sedating effects. Postoperative pain is effectively controlled with acetaminophen and topical anesthetic sprays. Postoperative monitoring for apnea, desaturation, and dysrhythmias is a necessity in sleep apnea patients. PMID- 1760170 TI - Unusual etiology of hyperkalemia in an immunocompromised patient. AB - Hyperkalemia was found in an immunocompromised patient undergoing emergency cystoscopy. The cause of the hyperkalemia was an intraperitoneal rupture of the bladder. This case report discusses conditions that predispose patients to bladder rupture and anesthetic management of hyperkalemia. PMID- 1760171 TI - Management of the challenging airway with the Bullard laryngoscope. AB - The Bullard laryngoscope is a rigid fiber-optic device that offers a new approach to oral laryngoscopy. In this report, I present five cases illustrative of the use of the Bullard laryngoscope in patients with demonstrated or suspected difficult laryngoscopy and intubation. PMID- 1760172 TI - Operation Desert Shield sequel: experience aboard the USNS Comfort during the Persian Gulf conflict. PMID- 1760173 TI - History of anesthesiology in Germany. PMID- 1760174 TI - Effects of instrument adjustments on quantitative echocardiographic gray level texture measures. AB - Quantitative echocardiographic gray level texture measures have proved useful in characterizing a variety of cardiac abnormalities, including contusion, ischemia, and cardiomyopathies. However, alterations of echocardiographic signal processing controls could potentially affect the resulting data. The purpose of this study was to assess the effect of common echocardiographic instrument adjustments on texture data. We imaged a graphite-in-gel phantom on five separate occasions, each time using 12 combinations of adjustments of transmit power, compression, and postprocessing curves over a clinically applicable range. Image texture was assessed using gray level run length and gray level difference texture measures; 42 individual measures were calculated. Significance of texture measure variations was assessed by analysis of variance. Changes in all three controls were associated with significant alterations in texture measures. Adjustments of transmit power and compression produced larger changes in texture measures than did adjustments of postprocessing curves. There were significant transmission compression-postprocessing interaction effects (p less than 0.05) for all but eight of the texture measures. For each texture measure, there were significant transmission-compression interaction effects (p less than 0.05). In summary, instrument adjustments had significant effects on quantitative texture measures, and these effects should be considered when evaluating quantitative echocardiographic gray level texture measures. PMID- 1760175 TI - Ultrasonic myocardial tissue characterization in the operating room: initial results using transesophageal echocardiography. AB - Ultrasonic tissue characterization provides quantitative assessment of myocardial function and viability. We have previously reported that normal myocardium is characterized by a diastolic-to-systolic cyclic variation of integrated backscatter (IB), whereas ischemic myocardium exhibits blunting of this pattern. To define the applicability of this measurement to characterize the left ventricular myocardium in the operating room, we studied 26 consecutive patients undergoing open heart surgery (12 coronary artery bypass graft, 13 valvular, 1 other) with 5 MHz transesophageal echocardiography. Images of the left ventricle were obtained in the short-axis plane (papillary muscle level) before cardiopulmonary bypass. M-mode acquisition of myocardial IB was attempted from the anterior and inferior segments in each patient. The cyclic variation of IB was measured in at least two consecutive cycles in addition to a qualitative assessment of wall motion. Quantitative measurement of IB was possible in 39/52 (75%) myocardial segments. Cyclic variation of IB averaged 5.7 +/- 1.4 dB (SD) in segments with normal wall motion (n = 25); no difference was noted in the cyclic variation of IB among anterior or inferior walls. Hypokinetic segments demonstrated significant reduction of the cyclic variation (3.8 +/- 1.8 dB; p less than 0.001). Difficulty with obtaining myocardial IB was related to near field artifact or lateral displacement of the left ventricular wall during systole. Transesophageal echocardiography holds promise for the evaluation of myocardial function and its preservation during cardiac surgery. PMID- 1760176 TI - Pulmonary venous flow velocity: relation to hemodynamics, mitral flow velocity and left atrial volume, and ejection fraction. AB - Abnormal pulmonary venous flow velocity patterns are present in multiple cardiac disease states, but the determinants of pulmonary venous flow velocity have not been fully elucidated. To determine the relative importance of several proposed factors that could influence pulmonary venous flow, anatomic, hemodynamic, and Doppler mitral and pulmonary venous flow velocity data were compared in 50 consecutive patients undergoing cardiac catheterization for clinical reasons. Pulmonary venous diastolic flow velocity was most strongly related to left ventricular isovolumetric relaxation time (r = -0.59), left ventricular end diastolic pressure (LVEDP, r = 0.50), left atrial minimum volume (r = 0.50), mitral deceleration time (r = -0.50), and early diastolic mitral flow velocity (r = 0.45). Pulmonary venous systolic flow velocity related best with left atrial minimum volume (r = -0.45) and left atrial ejection fraction (r = 0.44). Pulmonary venous systolic flow velocity integral also showed the strongest relation with left atrial minimum volume (r = -0.48). Relations between pulmonary venous flow velocity and velocity time integrals and other variables were sometimes significantly different, apparently caused in part to differences in heart rate. These results suggest that pulmonary venous diastolic flow velocity is influenced by the same factors that influence early left ventricular diastolic filling; pulmonary venous systolic flow velocity relates best to left atrial volume and atrial ejection fraction and does not relate to left ventricular ejection fraction. Future studies analyzing pulmonary venous flow velocity variables should include data on both peak velocities and velocity time integrals as well as left atrial size and function. PMID- 1760177 TI - Pulmonary venous flow in cardiac tamponade: influence of left ventricular dysfunction and the relation to pulsus paradoxus. AB - The pattern of left atrial filling was studied in nine closed-chest dogs during cardiac tamponade before and after production of microembolic left ventricular dysfunction produced by intracoronary injection of 54 +/- 4 microns (SD) microspheres. With cardiac tamponade, a significant increase in the ratio of systolic/diastolic pulmonary venous flow velocity integral both before (1.65 +/- 0.24 versus 2.77 +/- 0.43 [SE], p less than 0.05) and after production of left ventricular dysfunction (0.57 +/- 0.12 versus 1.77 +/- 0.44, p less than 0.05) was seen. Compared with baseline, cardiac tamponade caused a significant inspiratory decrease in systolic pulmonary venous velocity both before (7.3 +/- 2.0 versus 1.2 +/- 1.4 cm/sec) and after left ventricular dysfunction (3.4 +/- 0.4 versus 1.0 +/- 0.9 cm/sec, both p less than 0.05). The magnitude of respiratory variation (expiration-inspiration) of the pulmonary venous flow velocity integral with tamponade was significantly greater before than after left ventricular dysfunction (1.6 +/- 0.2 cm versus 0.8 +/- 0.2 cm, p less than 0.05). A significant correlation was found between the inspiratory fall in aortic systolic pressure and the flow velocity integral of pulmonary venous flow before left ventricular dysfunction (r = 0.58, p less than 0.05). After coronary embolization, neither pulsus paradoxus nor significant respiratory variation (expiration-inspiration) of the pulmonary venous flow integral was observed with cardiac tamponade. In this model of cardiac tamponade and left ventricular dysfunction, left atrial filling occurs predominantly during ventricular systole. These changes may be helpful in recognizing hemodynamically significant pericardial effusion and have implications for the pathophysiology of cardiac tamponade. PMID- 1760178 TI - Intracardiac two-dimensional echocardiography in patients with pericardial effusion and cardiac tamponade. AB - The utility of intracardiac two-dimensional echocardiography in the identification of pericardial effusion was assessed in five patients with pericardial effusion and cardiac tamponade. A 20 MHz, mechanically rotating ultrasound catheter was used for intracardiac imaging. In all five patients, intracardiac echocardiography yielded high resolution of images of the right atrial cavity, the right atrial wall, and the pericardial effusion. In two patients, right atrial collapse could be identified during real-time imaging. Although the entire right atrial cavity and the pericardial effusion could not be displayed in a single imaging field because of the limited depth of field associated with the 20 MHz catheter, manipulation of the catheter allowed visualization of the pericardial effusion and the parietal pericardium in each patient. The effusion was seen to surround the superior vena cava, as well, in all patients. After pericardiocentesis, the reduction in the size of the effusion and increase in the right atrial cavity size could be recognized by intracardiac echocardiography. The introduction and manipulation of the ultrasound catheter was easily performed without any complications. This experience presents one clinical application for intracardiac echocardiography and indicates its potential value in the invasive cardiac laboratory. PMID- 1760179 TI - Complications of transesophageal echocardiography in ambulatory adult patients: analysis of 1500 consecutive examinations. AB - Transesophageal echocardiography is a new approach that can be used to image cardiac structures. It combines two existing technologies: cardiac ultrasound and endoscopy. To obtain a cardiac image, the transesophageal probe has to be positioned properly within the esophagus. The first 1500 consecutive transesophageal echocardiographic examinations in ambulatory adult patients from one center were analyzed to identify conditions associated with failed esophageal intubation and procedural complications. Esophageal intubation was not achieved in 11 patients (0.73%). The reasons for the failure of intubation were operator inexperience, hypersensitive pharynx despite topical anesthesia, and cervical spondylosis. Six of those patients also had a history of dysphagia. Procedural complications were identified in seven patients (0.47%). Tracheal intubation was present in four patients, with immediate development of stridor and incessant cough in two patients. Atrial fibrillation developed in two patients--one had atrial myxoma and one had mitral stenosis. Bronchospasm developed during the transesophageal examination in one patient who was receiving long-term treatment for bronchial asthma. We conclude that transesophageal echocardiography is feasible in most adult patients in the ambulatory setting and that the complication rate is very low. Proper patient selection and preparation are crucial to the successful performance of this procedure. PMID- 1760180 TI - Color flow Doppler mapping studies of "physiologic" pulmonary and tricuspid regurgitation: evidence for true regurgitation as opposed to a valve closing volume. AB - Color flow Doppler mapping using either an Aloka 880 or a Toshiba SSH65A system was performed in 39 normal subjects (aged 13 to 45 years) and 43 patients (aged 13 to 82 years) with pathologic tricuspid or pulmonary regurgitation to evaluate the incidence of "physiologic" regurgitation of right heart valves and to determine the differentiating characteristics in the spatial distribution and velocity encoding of "normal" and "pathologic" regurgitant jets. In the normal subjects, tricuspid and pulmonary regurgitation were documented in 32 (83%) and 36 (93%), respectively, and were unrelated to the system being used. Flow acceleration and aliasing were imaged on the right ventricular side of the tricuspid regurgitant orifice and on the pulmonary artery side of the pulmonary valve (in both normal subjects and patients), and indicated flow convergence for true regurgitation through an orifice as opposed to blood being driven retrogradely by the closing valve. Such proximal acceleration was documented in all patients with pathologic tricuspid regurgitation, in 31/32 of the normal subjects with tricuspid regurgitation, and was also observed in 12/15 (80%) of the patients and 4/12 (33%) of normal subjects with pulmonary regurgitation who were examined with the Toshiba system. The dimensions (mean +/- SD) of tricuspid regurgitant jets (length [JL] and area [JA]) were consistently larger in the patients than in the normal subjects [JL: 3.4 +/- 0.9 vs 1.2 +/- 0.5 cm, p less than 0.001; and JA: 5.7 +/- 2.0 vs 1.4 +/- 0.7 cm2, p less than 0.001) as were the pulmonary regurgitation jet dimensions (JL: 1.8 +/- 0.4 vs 0.9 +/- 0.08 cm, p less than 0.001; JA: 1.8 +/- 0.7 vs 0.3 +/- 0.08 cm2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760181 TI - Transesophageal color flow Doppler mapping in the assessment of native mitral valvular regurgitation: comparison with left ventricular angiography. AB - Transesophageal echocardiography (TEE) was performed within 24 hours after cardiac catheterization in 45 patients for assessment of native mitral valvular regurgitation. Color flow mapping was used in evaluating systolic regurgitant jet sizes. A jet demonstrated by TEE was 96% sensitive and 44% specific for angiographic mitral regurgitation. The presence of angiographic mitral regurgitation was best predicted by (single measurement) (1) a holosystolic jet, (2) a jet length greater than 2.5 cm, and (3) a jet area greater than 2 cm2. Severe angiographic mitral regurgitation (grades 3 and 4) was best predicted by (single measurement) (1) a jet area greater than 5 cm2, and (2) a jet length greater than 4 cm. It is concluded that the assessment of angiographic mitral regurgitation by TEE is improved by the measurement of these jet parameters, which have a high sensitivity and higher specificity than the presence of a jet alone. Furthermore, with TEE one is able to differentiate severe (grades 3 and 4) from absent or mild mitral regurgitation (grades 0, 1, and 2). PMID- 1760182 TI - Comparison of intraoperative transesophageal echocardiography to epicardial imaging in children undergoing ventricular septal defect repair. AB - Intraoperative transesophageal echocardiography was compared with epicardial echocardiography after ventricular septal defect repair. This comparison was made in 18 children aged 7 to 137 months (median, 32 months), weighing 6.3 to 49.1 kg (median, 10.8 kg) from November 1989 to January 1991. Ventricular septal defect types were perimembranous (six), malalignment (seven), supracristal (three), midmuscular (one), and inlet (one). Eight children had isolated ventricular septal defects, four had tetralogy of Fallot, three had double outlet right ventricle, two had double chambered right ventricle, and one had pulmonary stenosis. Patch interrogation was complete in 17 of 18 transesophageal echocardiography and 16 of 18 epicardial echocardiography studies. Inability to fully interrogate the ventricular septal defect patch by epicardial echocardiography occurred in two children as a result of anterior ventricular septal defect location, limited epicardial exposure, and surgical hardware interference. Incomplete transesophageal echocardiography patch interrogation occurred in the child with the midmuscular ventricular septal defect. Seven residual ventricular septal defects were documented by color flow Doppler in six patients. Five of seven residual defects were demonstrated by both real-time transesophageal echocardiography and epicardial echocardiography imaging. Transesophageal echocardiography and epicardial echocardiography missed 1 and 7 defects, respectively. The missed defects were different with each technique and were confirmed by postoperative surface echocardiography. No residual defects of sufficient size to require reoperation were found as determined by combination color flow jet analysis and intraoperative oximetry (no pulmonary to systemic flow ratio was greater than 1.50). Patches caused two-dimensional and Doppler signal masking, but this was not limiting because all residual defects were found at the margins of the ventricular septal defect patch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760183 TI - Toxic methemoglobinemia caused by topical anesthetic given before transesophageal echocardiography. AB - Transesophageal echocardiography was performed on a patient with critical aortic stenosis and severe three-vessel coronary artery disease. Immediately after the procedure the patient experienced marked cyanosis (oxygen saturation of 53%) secondary to methemoglobinemia (methemoglobin saturation of 45%). Toxic methemoglobinemia was thought to be caused by topical anesthetic. He responded dramatically to treatment with intravenous methylene blue. Toxic methemoglobinemia should be suspected in unexplained cyanosis occurring after transesophageal echocardiography and other endoscopic procedures during which potentially causative agents have been used. PMID- 1760184 TI - Left atrial mass produced by extensive mitral annular calcification. AB - An unusual case of mitral annular calcification presenting as a left atrial mass is discussed. The differential diagnosis of left atrial masses with particular reference to their echocardiographic features is reviewed. PMID- 1760185 TI - Induction of wide QRS tachycardia during transthoracic echocardiography. AB - A wide QRS tachycardia was repeatedly triggered during transthoracic echocardiographic examination in a critically ill premature infant with bilateral chest tubes. The left-sided tube was anterior to the heart. The arrhythmia was not induced after removal of the chest tubes at the follow-up ultrasonographic evaluation. Compression of the thoracic wall and chest tube, and subsequently the heart, by the ultrasound transducer is postulated as the cause for this wide QRS tachycardia. PMID- 1760186 TI - Atypical pseudoaneurysm after mitral valve replacement: Doppler echocardiographic diagnosis. AB - Ventricular pseudoaneurysm is a rare complication of mitral valve replacement or myocardial infarction. Typically, a ventricular pseudoaneurysm appears as an echocardiographic lucency posterior and lateral to the left ventricle and is best seen from the parasternal long axis and apical four-chamber views. We present an atypical case of left ventricular pseudoaneurysm that tracts posterior and lateral to the right ventricle that was best visualized from the subcostal and low parasternal windows with medial angulation. Doppler imaging confirmed the diagnosis by demonstrating to-and-fro flow between the left ventricle and the cavity located behind the right ventricle. This case emphasizes the importance of the use of multiple echocardiographic windows. PMID- 1760187 TI - Transesophageal echocardiographic guidance of balloon atrial septostomy. AB - Two newborn infants with transposition of the great vessels and an intact ventricular septum were cyanotic when they underwent bedside balloon atrial septostomy in the neonatal intensive care unit. The procedure was conducted under direct transesophageal two-dimensional echocardiographic guidance. Success of the procedure was evaluated with color flow Doppler and the two-dimensional assessment of the septostomy. This procedure has advantages over catheterization and its attendant fluoroscopy, which usually are performed in the catheterization laboratory, expose the patient to radiation, and necessitate transportation of a patient who is hemodynamically unstable to an often distant catheterization laboratory. Transesophageal echocardiography has several advantages over transthoracic echocardiography in aiding this procedure. It provides an optimal view of the atrial septum, while keeping the chest exposed for observation of respiratory effort and for improved thermoregulation. PMID- 1760188 TI - Noncommunicating intramural hematoma: an indication of developing aortic dissection? AB - A 60-year-old patient was referred to the hospital for persisting chest pain. The first transesophageal echocardiogram showed localized hematomas without aortic dissection. Several days later the patient suffered complete paraplegia after a second episode of chest pain. The transesophageal echocardiogram now showed a complete aortic dissection. Thus whether intramural hematomas can be regarded as an early sign of impending aortic dissection needs to be investigated. PMID- 1760189 TI - Left ventricle-to-ascending aorta communication complicating composite graft repair undetected by aortography: diagnosis by transesophageal echocardiography. AB - A 57-year-old man underwent composite ascending aortic conduit and prosthetic aortic valve repair of a sinus of Valsalva aneurysm. The patient's course was complicated by recurrent aneurysm formation caused by a communication between the left ventricular outflow tract and the ascending aorta outside the conduit. Transesophageal echocardiography documented the anatomic and functional characteristics of this complication, whereas aortography failed to demonstrate them. Findings at surgery confirmed the transesophageal echocardiogram results of a left ventricular outflow tract to aorta communication, a normal prosthetic aortic valve, and an intact distal anastomosis of the conduit with the aorta. Transesophageal echocardiography is a useful modality for the evaluation of composite graft repairs of the aortic valve and ascending aorta. PMID- 1760190 TI - Thrombotic disc impediment in a Medtronic-Hall aortic valve prosthesis diagnosed by Doppler echocardiography followed by successful reoperation. AB - A case with impeded disc movement caused by thrombus formation in a Medtronic Hall aortic valve prosthesis is reported. A correct diagnosis, including both mechanism and severity of the prosthesis failure, was established by Doppler echocardiography. The patient was promptly referred for surgery without invasive or other supplementary investigations. PMID- 1760191 TI - Spontaneous left atrial echocardiographic contrast in mitral stenosis: early disappearance after valve replacement. AB - We describe a patient with mitral stenosis and severely enlarged left atrium. Transthoracic echocardiography showed a false image of intraatrial thrombus, whereas transesophageal echocardiography showed massive spontaneous left atrial contrast. Intraoperative transesophageal echocardiography was performed. During cardioplegic arrest the contrast was enhanced, but it gradually and completely cleared 15 minutes after cardiopulmonary by-pass arrest. Transesophageal echocardiography is a useful technique for the study of intraatrial masses and may bring a new dimension to tissue characterization studies. PMID- 1760192 TI - [Analysis of sister-chromatid exchange rate from peripheral lymphocyte of people exposed to environmental cadmium]. AB - Sister-chromatid exchanges (SCEs) were analyzed using peripheral lymphocyte from 38 persons (20 men and 18 women) who had been exposed to environmental cadmium (Cd), and 9 controls (7 men and 2 women). Correlations between SCE rates and urinary Cd-concentrations were done. There were no significant differences in SCE rates between the Cd-polluted and nonpolluted groups. There were no significant correlations between SCE rates and urinary Cd concentrations. PMID- 1760193 TI - [Studies of the expression of human interleukin-2 receptor cDNA in mammalian cells]. AB - Human interleukin-2 receptor cDNA was transfected into mouse fibroblast cells (L929) by using DNA-calcium phosphate coprecipitation method. Results from RNA dot-blot hybri dization, FITC-IL-2 fluorescent staining assay and anti-Tac specific rossette test demonstrated that the product of human interleukin-2 receptor cDNA in L929 cells is able to bind IL-2 and anti-Tac antibody. Moreover, the abnormal expression of IL-2R gene in T-cell leukemia cell lines such as Jukat cells and Molt-4 cells was analyzed and discussed. PMID- 1760194 TI - [A study of aneuploid induction by three mitotic arrestants in mouse bone marrow cells]. AB - Three mitotic arrestants, i.e., colchicine (COL), econazole(EZ) and hydroquinone (HQ) have been assayed by means of C-Mitotic (CM) effects, micronucleus (MN) and chromosomal aberration (CA) test for their effects of aneuploid induction in mouse bone marrow cells COL induced poly/aneuploid in mouse bone marrow cells. EZ was weakly positive in CM effects test but it may not induce aneuploid in mammalian cells. HQ could not only be a clastogen but also an aneuploid inducer. The results indicated that the comparative employment of the three cytogenetic criteria could be quite useful for detecting aneuploidy inducers in mammalian somatic cells in vivo. PMID- 1760195 TI - [Screening and isolation of the cerebellar specific expressed mRNA in mouse: subtractive hybridization by phenol emulsion reassociation technique]. AB - There are extremely complicated and numerous gene expressions in mammalian brains. Each region of the brain contains a set of mRNA expressed only in that region and these mRNA would be related to presumed region of specific function. Genes preferentially expressed in cerebellum (CB) are therefore the reasonable candioate genes for site of genetic lesions in CB neurodegenerative disorders. In this study, the subtractive hybridization was introduced into screening and isolating CB specific mRNA. Testing CB and front cortex (CTX) cDNA libraries were built, which covered most low abundantly expressed mRNA. By applying over 100 fold excessive CTX and liver single strand cDNA to the CB double strand cDNA, subtractive hybridization was carried out by phenol-emulsion-reassociation technique (PERT), in which the common expressed housekeep genes would be eluted by restrict site ligation, and CB specific cDNA flanking with EcoRI site in both ds cDNA ends could be cloned into lamda gill phage. PERT subtraction reduced CB cDNA libraries from initial 5.15 x 10(6) to remaining 2.5 x 10(3) recombinants, which were most likely CB specific expressed cDNA. Random Twenty recombinants (over 2 kb inserts) were amplified randomly by polymerase chain reaction (PCR) and were hybridized with CB cDNA and liver cDNA probes in dot blot. 14 inserts positively hybridized with CB cDNA probe and only 3 inserts showed signals with liver cDNA probe. Colony blot presented similar results. 10 cDNA clones which affinited to CB cDNA probe were selected for the Northern blot. In five tissures, 2 cDNA clones binded only in CB mRNA channel, 6 were proved preferential expression in CB and low abundant expression in 4 other tissues, 1 clone was a housekeep gene and 1 could not be detected in all tissues. The partially sequencing of clone PC7 and PD8 were introduced into Computer Gene Bank Data Base. No homologous complements were found between these two clones and over ten thousands genes that have been sequenced. The two clones were newly reported. According to our experiment, we believe that: 1) CB specifically expressed mRNAs are much less than expected comparing with other brain regions; 2) most of CB mRNA expressions are in a preferential way other than unique expression. PMID- 1760196 TI - [Subcloning and sequencing of the Streptomyces griseus DNA fragment with promoter activity in E. coli]. AB - A 410-bp DNA fragment of Streptomyces griseus No.45 with in vivo promoter activity in E. coli has been isolated by subcloning the cloning strain E. coli No.8-1. The result of sequencing shows that the promoter fragment contains 50.5% G + C bases. It has some repeat sequences. It shows good homology to the E. coli promoter consensus sequences in -10 and -35 regions. There are 18 bp between the two regions. It has two regions that are similar to SD sequence in E. coli and consensus sequence in SEP (Streptomyces-E.coli-type promoter) of Streptomyces lividans respectively. There is 1 Alu I site, 1 Cla I site, 2 Mbo I sites, 3 NlaIII sites and 1 PvuII site in the promoter fragment. PMID- 1760197 TI - [Studies of mtDNA of Ustilago maydis. I. Cloning and gene mapping]. AB - This paper covers the following studies of mtDNA of Ustilago maydis. (1) By inserting the Bam HI and Pst I fragments of the mtDNA into the corresponding sites of pBR322, we cloned a unique sequence of 49.6 kb, accounting for 89.3% of the mitochondrial genome (60.7 kb). (2) With heterogenous genes from plants or fungi as probes, we identified seven genes, and mapped them onto the restriction map of the mt DNA. The genes were arranged in such an order: -UmCOB-UmOXII-S-rR NA-UmOXIII-L-rRNA-UmATPase6-UmOXI-. (3) We tried to express the three cloned genes, UmOXII, UmOXIII, and Um-ATPase 6, in E. coli maxcel expression system, but no specific protein was observed. PMID- 1760198 TI - [Long-term follow-up of neonatal hyperbilirubinemia when phototherapy was withheld because of low bilirubin levels in the spinal fluid--growth, intelligence and soft neurological signs in school children]. AB - The significance of cerebrospinal fluid (CSF) bilirubin levels on the outcome of neonatal jaundice has been investigated by correlations between kernicterus or brain damage and CSF bilirubin levels (Torii 1974, 1981, Meisels 1984), This study is designed to clarify the significance of CSF bilirubin levels in the long term prognosis of neonatal hyperbilirubinemia. Sixteen full-term newborn babies with hyperbilirubinemia (serum bilirubin level 20.0-30.0 mg/dl) who did not receive phototherapy because of low bilirubin in their spinal fluid (usually under 0.5 mg/dl in normal neonates) were followed in this study of growth, intelligence and neurobehavior. The subjects' neurobehavior was compared with that of a matched control group. The physical growth of the children with a history of hyperbilirubinemia was within normal limits except for one girl whose weight was less than-2 SD from the average. Verbal IQ's were lower than performance IQ's in 10 out of 14 children with a history of hyperbilirubinemia. However, no mental retardation was noted. No significant difference was found between the two groups in mean positive scores on the Garfield test. In the Prechtl test, mean score of the finger-touching test was significantly higher in the children with a history of hyperbilirubinemia than in the control group. The soft sign coefficient and the occurrence of attention deficit hyperactivity disorder were not significantly different in the two groups. In summary, a low bilirubin level (less than 0.5 mg/dl) in the spinal fluid seems to be a good prognostic sign in infants with neonatal bilirubinemia. PMID- 1760199 TI - [A study of functional plasticity of the brain in childhood. I. Critical period dislodging lateralization of language in the brain]. AB - To investigate the functional plasticity of the brain in childhood, the intelligence and language tests, brain CT and dichotic listening test were performed on 34 patients with hemiplegia. All 13 patients with left hemiplegia, 8 to 37 years old, showed a right ear dominance suggesting the lateralization of language in the left hemisphere. Among 21 patients with right hemiplegia, 7 to 22 years old, 16 patients who had suffered from the left hemispheric damage before 6 years and 1 month of age, showed the left ear dominance suggesting the lateralization of language in right hemisphere except 2 patients. On the contrary, 3 patients with right hemiplegia who had suffered from the left hemispheric damage after 6 years and 6 months of age showed a right ear dominance. It was concluded that the critical period for the dislodging of language lateralization in the brain from the damaged left hemisphere to the intact right hemisphere is the first half of 6 years after birth. Five patients out of 8 patients with right hemiplegia showed significantly lower scores in performance than in verbal WISC IQ. The compensation of language function rather than performance function was considered to be characteristic for the left hemispheric damage in childhood. PMID- 1760200 TI - [Relationship between electroencephalographic abnormality and late blink reflex responses in infantile spasms and EIEE]. AB - Electrically elicited blink reflex (BR) were analyzed in seven patients with age dependent epileptic encephalopathies (5 patients with infantile spasms and 2 with EIEE). Four patients with infantile spasms showed prolonged latency of the late BR responses (R2). In 2 patients with EIEE showing suppression burst pattern on EEG, R2 was not detectable. R2 abnormality in BR might reflect the dysfunction of the brainstem reticular formation in age dependent epileptic encephalopathies. PMID- 1760201 TI - [Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery. III. Investigation in hydrocephalus (Part 2)]. AB - We made 10 measurements of Pourcelot's index of resistance (RI) in the anterior cerebral artery (RI-ACA) and basilar artery (RI-BA), and RI ratio (= RI-ACA/RI BA) in seven cases of hydrocephalus before and after treatment. The mean values of RI-ACA (0.831 +/- 0.050, mean +/- SD), RI-BA (0.800 +/- 0.053) and RI ratio (1.039 +/- 0.030) before treatment were significantly higher than in normal infants. Two hours after treatment, the mean RI-ACA (0.654 +/- 0.099) was lower than in normal infants, and RI-BA (0.684 +/- 0.101) were normalized. Before treatment, the mean value of RI-ACA was higher than that of RI-BA. All RI ratios were higher than 1.00. After treatment, the mean RI-ACA was lower than the mean RI-BA. All RI ratios were normalized and lower than 1.00 (0.957 +/- 0.024). PMID- 1760202 TI - [Quantitative evaluation of pseudohypertrophy in Duchenne muscular dystrophy]. AB - In order to evaluate pseudohypertrophy of the calves in Duchenne muscular dystrophy (DMD) quantitatively, we measured the circumference of the thigh, knee, calf, and ankle in total 7 patients with DMD whose ages ranged from 3 to 5 years, and 165 healthy boys aged 3 to 6 years. Simple value of the calf circumference was not useful to evaluate pseudohypertrophy in DMD, because the circumference was variable following to the nutrition (Kaup index) in healthy boys. Various ratios were then tested for the calf circumference in relation to the thigh, knee, or ankle circumference. Of these, the calf/knee circumference ratio was the most informative; the values of 13 out of 14 affected legs were above the mean + 2SD. PMID- 1760203 TI - [The occurrence of destructive hydrocephalus in cases with neonatal intraventricular hemorrhage]. AB - A total of 21 neonates with intraventricular hemorrhage (IVH) were studied; 12 (57.1%) survived, and 7 (58.3%) of these 12 cases suffered from hydrocephalus. Hydrocephalus occurred only in patients with IVH of grades III and IV on Papile's classification, and its occurrence rate was 87.5% as the sum total for the two groups. Destructive hydrocephalus (DHC) occurred in 5 cases of grade III and grade IV, and its occurrence rate was 62.5% as the sum total for the two groups. It could be conjectured that the prognosis of the IVH depends upon the extent of the primary hemorrhagic lesions. However, in cases with DHC, the resistance of the cerebral parenchyma to the hydrodynamic force is decreased, so that secondary cerebral destruction yielding rapid and intense ventricular dilatation, which is responsible for the development of neurological disorders, might occur more easily than in cases with IVH of grades III and IV, and to the secondary parenchymal destruction that may arise in association with hydrocephalus. It is essential that a shunt operation should be performed as soon as possible after the diagnosis of DHC has been established so as to allow repair of the primary lesion and to minimize the secondary brain damage. PMID- 1760204 TI - [Facilitation and recovery of the H-reflex in children]. AB - Facilitation and recovery of the H-reflex were studied in 63 children with cerebral palsy, and the results were compared with those obtained for 60 normal children. H waves were recorded from the gastrocnemius with surface electrodes, after applying paired stimulations to the tibial nerve in the midpopliteal crease. In normal children, both the facilitation and the recovery showed a tendency to decrease with their development, while those for children with cerebral palsy were more marked than normal children in all age groups. The present study indicated that the excitability of spinal alpha motoneurons and the subliminal fringe in the motoneuron pool might change due to the maturation of and the damage to the central nervous system in children. We consider that H reflex examination provides useful information for the supraspinal control to the spinal mechanism to regulate muscle contraction in children as well as in adults. PMID- 1760205 TI - [Clinicoencephalographic study of periodic lateralized epileptiform discharges in infants]. AB - The mechanism of periodic lateralized epileptiform discharges (PLEDs) still remains unclear, although it has been the subject of a number of theories. We investigated the relationship between the level consciousness and PLEDs in order to clarify both the clinical significance and the mechanism of PLEDs. We studied two neonates and two infants with acute organic lesions of the brain (cerebral infarction, meningoencephalitis, cerebral hemorrhage, acute infantile hemiplegia), of whom all showing PLEDs in EEG. In each case, we analyzed sequential EEG records and the level of consciousness, and measured the periodicity, voltage and duration of PLEDs by a computer controlled digitizer. In each case, the periodicity and voltage of the discharges were related to the level of consciousness. The appearance rate of PLEDs was relatively high at the level of consciousness from III-100 to III-200. The inverse correlation between the frequency (1/periodicity) and the voltage of PLEDs was significant in 53% of the total records of PLEDs; it was also frequently observed at the level of consciousness between III-100 and III-200. From above findings we concluded that an appropriate degree of damage to produce PLEDs is required in both the cerebral cortex and subcortical white matter corresponding to the level of consciousness from III-100 to III-200. PMID- 1760206 TI - [The clinical effect of mechanical ventilatory assistance with tracheotomy in terminal phase muscular dystrophy]. AB - The clinical effect of mechanical ventilatory assistance with tracheotomy in respiratory failure of terminal phase muscular dystrophy was studied. The subjects were 6 Duchenne muscular dystrophy cases and 1 Ullrich type congenital muscular dystrophy case. Duration of the longest survival case was 4 years and 5 months. General physical conditions, complications, ADL and muscular atrophy were examined. By ventilatory assistance respiratory failure improved, and the physical condition stabilized and took good progress. Arterial hemorrhage which is lethal complication was observed in 2 cases. Mechanical ventilatory assistance with tracheotomy is an effective symptomatic therapy for the improvement of respiratory failure that can be applied when life prolongation is wished for by the patients or their families. PMID- 1760207 TI - [Cerebro-oculo-hepato-renal syndrome (Arima's syndrome) with slowly progressive renal insufficiency and epilepsy]. AB - We reported an additional case of Arima's syndrome with slowly progressive renal insufficiency and epilepsy. The patient is a 20-year-old man whose parents are consanguineous. He had a history of mild asphyxia at birth, and unexplained tachypnea developed during the neonatal period. But it disappeared later, and he have had no respiratory problem since then. Physical examination on admission at the age of 19 years revealed bilateral blephaloptosis, narrow palate, searching nystagmoid movement, absence of light reflex, muscle hypotonia and wasting of extremities. Funduscopic study showed optic hypoplasia, choroid coloboma and narrowing of vessels. Head CT scan showed agenesis of cerebellar vermis and hypoplasia of brainstem. CT scan and echography of the kidney disclosed the bilateral multiple cysts. Liver was hyperechoic in echographic study; this finding is consistent with fatty change. EEG showed dysrhythmic slow wave activity with sporadic spike and wave complex. Compared with previously reported cases, the present case has the following features: (1) slowly progressive renal insufficiency, (2) generalized tonic clonic convulsion developing from the age of 11 months, (3) ABR abnormalities including the right-sided shortening of wave I II interpeak latency and bilateral ill-defined wave V. Slow progress of renal failure in our case may reflect the mild pathological process of the kidney with sparing functional nephrons. It shows the diversity of the kidney pathology in Arima's syndrome. Epilepsy is a less common association in the syndrome, whereas EEG abnormalities were reported. ABR abnormalities may reflect the morphological alteration of the brainstem structure including auditory pathway. In our case it is uncertain whether the neonatal tachypnea was due to birth asphyxia or brainstem malformation responsible for abnormal respiration as suggested in Joubert's syndrome. PMID- 1760208 TI - [99mTc-HMPAO SPECT in epileptic disorders in childhood]. AB - Single photon emission tomography (SPECT) using Tc-99m-d,1 hexamethylpropylenamine oxime (HMPAO) was performed in two children with epileptic disorders during both sleeping and waking diurnal stages. Immediate postictal and interictal SPECT scans were obtained for a child with partial epilepsy. They demonstrated an interictal decrease in the regional cerebral blood flow (rCBF) and a more remarkable immediately postictal decrease in rCBF. The focus was in the same region of the SPECT for both interictal and postictal spikes. Another patient was diagnosed as having continuous spike-waves during slow sleep without epileptic seizures. Although SPECT during wakefulness showed no asymmetry, SPECT during sleep revealed decreased rCBF at the same location as the predominant area of diffuse epileptic discharges. We conclude that HMPAO SPECT is useful in investigation of the etiological mechanisms of seizures and epileptic discharges in epileptic disorders in childhood. PMID- 1760209 TI - [MELAS without ragged-red fibers: a case report]. AB - A female patient who had clinical characteristics of MELAS but with no apparent muscle symptoms was reported. She was in good health until 12 years and 5 months of age when she began to have afebrile generalized tonic-clonic convulsions. Thereafter, she had repeated stroke-like episodes, including headache, vomiting, convulsions, hemiparesis and left ehemianopsia. She had neither muscle weakness, fatigability nor atrophy. Laboratory examinations disclosed elevated lactate and pyruvate levels in the serum and cerebrospinal fluids, transient focal low density areas on brain CT and right sensorineural deafness by audiometry. No ragged-red fibers (RRF) were found in the first biopsy at 13 years and 6 months of age, and two RRF-like fibers containing red granular materials in the subsarcolemnal regions in the second at 15 years and 3 months of age. A biochemical assay on the two biopsied muscles demonstrated normal enzyme activities in the mitochondrial electron transport system. She was diagnosed as having MELAS because of remarkable mitochondrial abnormalities in smooth muscle cells in the intramuscular arterioles which were clearly demonstrated by succinic dehydrogenase (SDH) stain and on electron microscopy. It was suggested that the stroke-like episodes in this patient were induced by a preferential damage to the mitochondria in the blood vessel walls. Thus, we conclude that a simple method of identifying the strongly SDH-reactive blood vessels (SSV) in frozen sections is critical in supporting or making diagnosis of MELAS. PMID- 1760210 TI - [A case report of childhood multiple sclerosis with periodic synchronous discharge on EEG]. AB - A 12-year-old girl with multiple sclerosis (MS) with periodic synchronous discharge (PSD) on electroencephalogram (EEG) is reported. The patient developed clonic seizure of both arms at the age of 10. The muscle strength of left hand and both legs were decreased and her school records were declined at the age of 12. On neurological examination, the patient showed mild intellectual disturbance, mild weakness of face and extremities and bilateral decreased DTRs. Her gait was slightly ataxic. Cerebrospinal fluid (CSF) revealed an oligoclonal band. Serial CT scans disclosed ring enhancements in the regions corresponding to clinical symptoms (right central gyrus on Sep. '85, right lower and middle temporal gyri, and mesial site of occipital lobe on Oct. '85, right cerebellum on Jan. '86). The same lesions were visualized as a high signal intensity on T2 weight images and as a low signal intensity on T1 weight images on MRI. The attack of seizure occurs more frequently in children with than adults with MS. However, as far as we know in the cases of children with MS, there were no reports of PSD which was usually seen in the cases of subacute sclerosing panencephalitis. The pathomechanism of PSD is speculated to be suffered from subcortical damage. PMID- 1760211 TI - [Pedaling automatism in atypical West syndrome: a case report]. AB - A seven-month-old girl with atypical West syndrome with pedaling automatism was reported. She started to have early infantile epileptic encephalopathy with suppression-burst (EIEE) at age 14 days followed by infantile spasms at 3 months of age. She began to have spasms with automatism at 4 month, mainly consisting of pedaling movements of both feet associated with tonic spasms of upper extremities and writhing of trunk. Ictal EEG showed irregular slow waves with occasional spikes predominantly over the right hemisphere mixed with artifacts. Interictal EEG during sleep showed suppression-burst patterns. Cerebral atrophy and microcephaly were revealed on brain CT, immature myelination on MRI and decreased blood flow in the frontal, temporal, and parietal lobes on the right on PET scan. Pedaling automatism is rare in infancy and its clinical significance was discussed in relation to West syndrome and complex partial seizures. PMID- 1760212 TI - [A case of alternating hemiplegia in infants with CT abnormalities before onset]. PMID- 1760213 TI - [Muscle pathology in a girl with Marshall-Smith syndrome]. PMID- 1760214 TI - [A case of Hallervorden-Spatz syndrome--clinical course and successive findings of brain CT]. PMID- 1760215 TI - The epithelium of the rabbit vagina: a microtopographical study by light, transmission and scanning electron microscopy. AB - In order to obtain a more precise microtopographical surface map of the epithelium of the rabbit vaginal mucosa, investigations by light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) have been systematically correlated. The epithelium was examined from the "portio vaginalis cervicis uteri" down to the "vestibulum". This study shows that the upper 2/3 of the vagina--which, in this species, is very long, measuring 13-14 cm -is lined by a single epithelial layer of tall ciliated and microvillous cells closely resembling the endocervical epithelium with which it is continuous. Moreover, these ciliated and microvillous cells also cover mucosal infoldings in the upper part of the vagina, especially those on the ectocervix and in the fornices, and scattered vaginal crypts. In particular, the ciliated elements decrease in number below the fornices, so that in large areas of the middle part of the vagina only microvillous cells are recognizable. Prior to the squamo columnar junction, however, the ciliated cells increase again. This study also reveals that in the rabbit the squamo-columnar junction is located at the level of the pubic symphysis and that a squamous pluristratified epithelium covers only the lower 1/3 of the inner surface of the vaginal wall. In the estrous, i.e., precoital rabbit, the microvillous cells show little sign of secretion, whereas after mating they exhibit remarkable secretory features. These seem to increase progressively with postcoital stages (5 h, 24 h and 10 days) in the form of extensive mucification. These secretions often come in contact with spermatozoa retained in the mucosal infoldings and crypts, and are similar to those occurring in the endometrium, where they clearly depend upon progesterone activity. These epithelial features, different from those of other mammals, including humans, suggest that the greater part of the rabbit vagina accomplishes functions other than serving for copulation and as a fetal passageway. The present findings support the view that the rabbit vagina also plays a role as a reservoir of spermatozoa and in maintaining their viability, like the endometrium and endocervix. PMID- 1760216 TI - Postnatal changes in nerve cells and myelinated fibers in the pineal gland of cotton rats (Sigmodon hispidus). A light microscopic study. AB - Intrapineal neurons and intracapsular and intrapineal myelinated fibers were studied by light microscopy in male cotton rats (Sigmodon hispidus) at various postnatal ages. Until 300 days of age, neurons are encountered mainly in the distal third of the organ; neuronal nuclei are largest in this region. The remaining regions contain only a few neurons with smaller nuclei. In all regions, nuclear sizes of the neurons increase, and neuronal numbers reduce by half until 100-200 days. Neurons thus consist of different populations of cells, and the aging changes in neuronal nuclei seem to be related to the differentiation of the organ. The disappearance of neurons and the enlargement of the nuclei of remaining neurons proceed simultaneously with age. Intracapsular and intrapineal myelinated fibers appear at 20 days and their density increases with age. As the myelinated fibers are distributed mainly in the distal region and its capsule, these fibers are related topographically to intrapineal neurons. The intracapsular myelinated fibers continue into bilateral bundles of myelinated fibers found under the transverse sinuses, corresponding to the nervi conarii. Since the intracapsular fibers and the fibers traced between the capsule and the parenchyma bifurcate in a proximal direction, the intracapsular fibers are considered to run proximally, some entering the organ. PMID- 1760217 TI - Flagellum abnormalities of spermatozoa in seminiferous tubules after a short term vasectomy. AB - Electron microscopic observation was performed to examine whether spermiogenesis in the hamster might be affected by a short term vasectomy. When viewed by light microscopy, spermiogenesis was temporarily inhibited at 2 weeks, though to a limited extent among individuals, and had apparently recovered to the control level at 4 and 8 weeks after vasectomy in all hamsters. It was revealed at the electron microscopic level that mature spermatozoa with an abnormal flagellum were intermingled among numerous normal spermatozoa. The flagellum of the mature spermatozoa was composed of four different components: a mitochondrial sheath, outer dense fiber, fibrous sheath and axoneme. Abnormalities of the mitochondrial sheath were of three types: its discontinuity, displasia and deformation. The appearance of these abnormalities increased with the time after vasectomy and finally reached 52% as the highest value at 8 weeks. Additional noteworthy findings were the bisectioning of the outer dense fibers 2, 4 and 7, the fusion of two or three fibers, and the partial deletion of the fibrous sheath. These defects were characteristic in the vasectomized hamsters. Possible correlating microenvironmental factors are discussed as to how these abnormalities of the four flagellar components occur in the vasectomized hamsters. PMID- 1760218 TI - Effects of dietary zinc deficiency on protein secretory functions of the mouse testis. AB - The effects of dietary zinc deficiency on testicular protein secretion, mainly that by Sertoli cells, were examined by electron microscopy and two-dimensional polyacrylamide gel electrophoresis of [35S] methionine-labeled secretory proteins from mouse testes. Zinc deficiency caused a significant decrease in the gonadosomatic index and a distinct increase in deoxyribonucleic acid concentration. Sertoli cells maintained normal fine-structural features; junctional complexes among Sertoli cells continued to divide seminiferous tubules into basal and adluminal compartments in the zinc-deficient mouse testes. Severe atrophic changes were observed in spermatogenic cells after meiotic division in the adluminal compartment, but not in spermatogonia located in the basal compartment. Zinc replacement treatment caused spermatogenesis to recover normally. Although total protein secretion was not affected by zinc deficiency, one polypeptide spot appeared due mainly to the loss of its target spermatogenic cells. The present study indicates that zinc is indispensable for spermatogenic cells after meiosis and that testicular protein secretory functions can be preserved in the absence of zinc. PMID- 1760219 TI - Short-term mineralization of dentin and enamel in the mouse embryonic molars cultured in serum-free, chemically-defined medium. AB - The present study was designed to demonstrate the short term mineralization of dentin and enamel, and to investigate the effects of sodium beta-glycerophosphate (Na-beta-GPO4) on calcification in a serum-free, chemically-defined medium. The first mandibular molars at the bell stage dissected from 18-day-old mouse embryos were used as explants, which were cultured by an improved flotation method. Calcification of enamel in the 18-day-old embryonic molars occurred within the 6th day of culture. In another experiment, the molar germs were cultured in a serum-free, chemically-defined medium supplemented with 1, 5 and 10 mM Na-beta GPO4. Promotion of tooth mineralization was recognizable at very low concentrations, such as 1 mM Na-beta-GPO4, in 18-day-old embryonic tooth germs. The culturing system reported here shortens the time required for dentin and enamel calcification to one half or one third of that reported previously and therefore should prove useful for examining regulations for cytodifferentiation and morphogenesis in tooth germs and the mineralization of dentin and enamel. PMID- 1760220 TI - A unique fibrillar coat on the surface of migrating human primordial germ cells. AB - Primordial germ cells (PGCs) were studied by electron microscopy in human embryos at 27 and 30 days of gestation. PGCs were mainly found in the hindgut epithelium, some at the stage of separation from the endoderm, and others in migration through the mesenchyme of the dorsal mesentery between the primitive intestinal wall and the coelomic epithelium, including the coelomic angle. A few PGCs were still located in the endodermal epithelium. Before the process of separation and migration, PGCs appeared clearly different from neighboring somatic cells (endodermal, mesenchymal and epithelial cells of the hindgut and the coelomic layer). PGCs located in the endodermal epithelium were large and showed an irregular cell body often provided with filopodia-like processes that contacted somatic cells to form small areas of focal junctions. As a rule, PGCs possessed a large, round nucleus containing one or two conspicuous nucleoli. Lipid droplets, abundant glycogen particles, ribosomes and mitochondria were often observed in their cytoplasm. A detailed ultrastructural analysis revealed a delicate fibrillar coat frequently present on the free surface of PGCs during their migratory phase through the mesenchyme of the dorsal mesentery. This surface coat, likely corresponding to a glycocalyx, appeared as a particular, conspicuous filamentous layer of 30 nm thickness, mainly in the leading pseudopodial projections of PGCs migrating toward their target. The surface coat of PGCs can be associated with the binding sites of specific macromolecular components of the extracellular matrix, including fibronectin, and hence plays a role in PGCs recognition and migration during this special embryonic phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760221 TI - Differential changes in expression of the neurofilament triplet protein immunoreactivity in Purkinje cells of the cerebellum during the postnatal development of rats. AB - By means of peroxidase-anti-peroxidase (PAP) immunohistochemistry with both the neurofilament (NF) triplet (small: 68 K, medium: 150 K, high: 200 K) antisera and the antiserum against spot 35-calbindin, developmental changes in expression of the immunoreactivity for the NF triplet proteins in different domains of the Purkinje cells was examined in the cerebella of postnatal rats. From birth till the postnatal day 6 (P6) the somata and dendrites exhibited moderately positive immunoreaction for small and medium NF subunits. In contrast, the incubation for the high NF subunit resulted in a negative immunoreaction for the somata and dendrites of the Purkinje cells at those stages. On P8 and P10 they were weakly immunoreactive for all NF triplet. Thereafter the intensity of their immunoreaction decreased progressively and the Purkinje cell somata and dendrites were immunonegative for all NF triplet proteins on P21, when the Purkinje cell attained an adult appearance in morphology. On the other hand, the Purkinje cell axons, which can be identified selectively by the positive immunoreaction for the spot 35-calbindin throughout the course of the postnatal development, exhibited positive immunoreactivity for all the NF triplet on the 9th, 21th and 50th postnatal days in the cerebellar white matter. The development of the slow axoplasmic transport and the posttranslational modification of the NF triplet proteins are discussed as possible mechanisms underlying the differential expression of the immunoreactivity for the NF triplet proteins in different domains of the Purkinje cells during postnatal development. PMID- 1760222 TI - Novel honeycomb structures among collagen bundles in the Golgi tendon organs of the Chinese hamster. AB - A number of novel honeycomb structures were encountered among collagen bundles in the capsule lumen of the Golgi tendon organs in the adult Chinese hamster. They varied in size and shape and consisted of a hexagonal aggregation of columnar components (or units), usually perpendicularly disposed with respect to the long axis of the tendon organ. They measured 90-100 nm along their inner diameter and less than 1.0 micron in length, separated by partitions of electron dense materials about 30 nm wide. Each columnar unit consisted of a central, globular, electron dense material (20-30 nm in diameter) with a constant periodicity of 30 40 nm and many (16-20) radially-arranged filaments (about 6 nm in diameter), showing a flower-like pattern. The honeycomb structures were attached to or fused with collagen fibrils or fibers at their margins, and were also attached to the microfibrils and basal laminae of the sensory endings, Schwann cells, and the innermost cell layer of the outer capsule. These findings suggest that the honeycomb structures might contribute to a complicated three-dimensional connection of collagen bundles as a whole, and that this connection might efficiently cause the mechanical deformation of the sensory endings by their squeezing in muscular contractions or passive stretching. PMID- 1760223 TI - A scanning electron microscopic study of the intercalated portion of the biliary system in the rat liver. AB - The intercalated portion of the rat liver was studied by scanning electron microscopy (SEM) after removal of interlobular connective tissue by acid or alkaline hydrolysis. Biliary intercalated portions have generally been regarded as short straight links lying between the bile capillary network and the interlobular duct. The biliary system as observed by SEM lacked such specialized segments for linking. Instead, it contained long intercalated ductules taking winding and branching courses. The ductular branches frequently anastomosed with each other to form an extensive plexus along the limiting plate. The ductules repeatedly connected with the plate on their courses as well as at their terminals. This disposition of the ductules probably potentiates their tolerance to luminal obstruction. At the junction between the ductule and the limiting plate, ductular cells and hepatocytes shared the biliary lumen. The lumen sometimes approached the base of the ductule, providing a possible route for bile leakage. The intercalated ductule was composed of low fusiform epithelial cells throughout its length, meeting its classical criteria by light microscopy. Its basal surface was furrowed with narrow grooves along cell boundaries. The ductular cells extended numerous microplicae in the basal grooves and on their lateral surfaces, suggesting their secretory function. PMID- 1760224 TI - Post-embedding immuno-electron microscopy with rapid freezing and freeze substitution techniques for the localization of manganese superoxide dismutase. AB - Dehydration of specimens with ethanol or acetone makes it impossible to detect manganese superoxide dismutase (Mn-SOD) by immunohistochemistry. To circumvent obstacles and demonstrate localization by post-embedding immuno-electron microscopy, a rapid freezing and freeze-substitution technique was employed using Lowicryl K4M embedding medium. This was effective enough to allow the specific observation of immunogold particles for Mn-SOD on the mitochondria of cardiac muscle cells and WI-38 cells (human normal fetal lung diploid cells). This method preserved the antigen-antibody binding activity of Mn-SOD even after dehydration. Therefore, rapid freezing and freeze-substitution is useful for post-embedding immuno-electron microscopy of Mn-SOD and can further be employed for other antigens previously difficult to detect by conventional methods. PMID- 1760225 TI - Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. PMID- 1760226 TI - Antigenic domains of the HIV-1 vif protein as recognized by human sera and murine monoclonal antibodies. AB - To analyze the vif antibody response in individuals infected with the human immunodeficiency virus type 1 (HIV-1) and to determine antigenic epitopes on the vif protein, 104 HIV-1+ sera were screened for reactivity with a recombinant vif protein; 30 (28.8%) of these sera recognized the recombinant vif protein in immunoblot and were employed, together with 17 HIV-1/vif-negative control sera, in an enzyme immunoassay (EIA)-based epitope scanning assay with 183 overlapping decapeptides that covered the complete amino acid sequence of the HIV-1 vif protein (strain BH10). Of the 30 HIV-1/vif+ sera, 87% reacted with decapeptides comprising the two following epitopes: IEWRKKRY (vif amino acids 87-94) or DRWNKPQ (vif amino acids 172-178). The two epitopes were 89% and 100% conserved among different HIV-1 strains and their antigenicity could be confirmed by computer-assisted predictions of vif antigenic determinants. All the sera reactive with recombinant vif protein and with vif peptides originated from patients in CDC stages III or IV. Two murine anti-vif monoclonal antibodies reacted only with the seven C-terminal amino acids of the vif protein (SHTMNGH), which were not recognized by any of the human sera. Our results may be useful for further studies of vif seroreactivity and for the production of anti-vif mono- or polyclonal antibodies using vif peptides. PMID- 1760227 TI - In vivo sequence variation of the human immunodeficiency virus type 1 env gene: evidence for recombination among variants found in a single individual. AB - To assess in vivo sequence heterogeneity of the human immunodeficiency virus type 1 (HIV-1) env gene, we used the polymerase chain reaction to amplify proviral sequences present in peripheral blood mononuclear cell DNA of a patient with acquired immunodeficiency syndrome (AIDS). The amplified env gene fragment (575 bp) contains the first hypervariable region and part of the first conserved region. Eleven and twelve clones were sequenced, respectively, from specimens collected two months apart. Notable heterogeneity was observed among sequences recovered from both specimens. Also, the proviral population recovered from the first specimen varied significantly from that found in the second specimen. Both specimens contained forms with and without an 18 bp duplication. The presence or absence of this duplication, in addition to several point mutations, appear to define two molecular groups evolving in parallel within this patient. Several genotypes which had sequences characteristic of both groups occurred primarily in the second specimen; these can best be explained by multiple recombinational events between representatives of the two groups during reverse transcription. This study demonstrates that recombination may contribute significantly to the generation of diversity among HIV variants within a single individual. PMID- 1760228 TI - Human chromosome-dependent and -independent pathways for HIV-2 trans-activation. AB - Human immunodeficiency virus (HIV types 1 and 2) replication is controlled by the interaction of viral-encoded regulatory proteins and host cellular proteins with the viral long terminal repeat (LTR). The presence of HIV-1 and HIV-2 trans activator proteins, tat1 and tat2, respectively, greatly increases viral gene expression from their homologous LTRs. It is unclear if the cellular factors that support tat1-directed trans-activation of the HIV-1 LTR are the same for tat2 trans-activation of the HIV-2 LTR. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV-1 and HIV-2 tat-directed transactivation. DNA transfection experiments showed that the presence of human chromosome 12 in human-hamster hybrid clones was necessary for high-level tat-directed trans-activation of the HIV-1 and -2 LTR. Cross-trans activation of the HIV-2 LTR by tat1 was found to be chromosome 12 independent. In addition, chromosome 12 did not support trans-activation of another human retrovirus (human T-cell leukemia virus type I). Our results suggest that HIV-1 and -2 have evolved to employ a cellular pathway(s) encoded on human chromosome 12 for supporting homologous tat-directed trans-activation. Trans-activation of the HIV-2 LTR by tat1 in chromosome 12-minus cells suggests that multiple cellular pathways can be recruited to trans-activate the HIV-2 LTR and that these pathways may have been important in an HIV-like progenitor virus. PMID- 1760229 TI - Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells. AB - Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined. PMID- 1760230 TI - Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins. AB - Nucleotide sequences for long terminal repeat (LTR), gag, the protease gene, and pol of a human T-lymphotropic virus type 1 (HTLV-1) isolate of probable Caribbean origin (HTLV-1CH) and a Zairian isolate (HTLV-1EL) were determined providing complete proviral sequences for these isolates. These sequences were compared with those available from previously analyzed isolates. Nucleotide sequence differences of 1.2-3.3% were identified among isolates for which complete genetic information was available. Nucleotide sequence diversity was distributed relatively evenly over the genome with 1.3-5.2% differences in the LTR, 1.1-2.9% differences in gag, 0.7-2.1% differences in the protease gene, 0.9-2.5% differences in pol, 0.9-2.4% differences in env, 0.0-1.4% differences in rex, and 0.1-2.6% differences in tax. There were 1.2-2.3% amino acid differences overall, with 0.8-1.6% nonconservative amino acid alterations. Nucleotide differences were not found in regions of the LTR which are important for transcriptional activity or Tax response. Within the Rex-response element, nucleotide differences were found predominantly in loop rather than stem structures, thus, maintaining the overall secondary structure necessary for Rex activity. Evolutionary tree analysis of the sequence differences suggests a predominant clustering of different HTLV1 strains according to geographical origin. An open reading frame was also identified on the minus DNA strand situated between the env and rex/tax genes which exhibits 0.1-6.9% nucleotide sequence variation among HTLV1 strains. The limited sequence variation among HTLV-1 strains is in striking contrast to the extensive heterogeneity seen among human immunodeficiency virus (HIV) strains. PMID- 1760231 TI - Differential alteration of the anti-HIV-1 effect of phosphorothioate oligonucleotide S-dC28 by AZT, interferon-alpha, and dextran sulfate. AB - The combination of S-dC28 (a phosphorothioate oligodeoxcytidine 28 mer) with AZT, recombinant interferon alpha-A (IFN-alpha A) or dextran sulfate (DS) against replication of human immunodeficiency virus type 1 (HIV-1) were studied in MT4 cells, using both p24 core antigen and reverse transcriptase (RT) assays. Under the standardized conditions, the anti-HIV-1 dose-effect relationships of all test drugs showed sigmoidal curves with the following EC50 values: for the p24 core antigen assay, S-dC28, 0.03 microM; AZT, 0.004 microM; IFN-alpha A, 9.2 U/ml; DS, 0.26 micrograms/ml; for the RT assay, S-dC28, 0.04 microM; AZT, 0.01 microM; IFN alpha A, 11.6 U/ml; and DS, 0.31 micrograms/ml. A computer software based on the median-effect principle and isobologram techniques were used to quantitatively analyze drug interactions by calculating the combination index (CI) where CI less than 1, = 1, and greater than 1 indicates synergism, additive effect and antagonism, respectively. For p24-ELISA, the interaction of S-dC28 and AZT in combination produced a slight antagonism on HIV-1 replicative inhibition with CI values of 1.29-1.10; for RT assays, at EC50-EC95 levels, the CI values are 1.96 1.11. For p24 core antigen assay, the combination of S-dC28 with IFN-alpha A exhibited a dose-dependent anti-HIV synergism with CI values of 1.15-0.87 at EC75 EC95 levels. The RT assays for the same combination showed a broad synergistic effect with CI values of 0.62-0.60, at EC50-EC95 levels. S-dC28 plus DS showed a nearly additive effect based on both assay methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760232 TI - Proliferative response of mononuclear cells from HIV-infected patients to B-cell mitogens: effects of lymphocyte subset frequency, T-cell defects and prostaglandins. AB - Proliferative responses of mononuclear cells from patients seropositive for human immunodeficiency virus to B-cell mitogens are severely depressed compared with those of controls. The role of several immunoregulatory phenomena was analyzed. Experimental results show that addition of exogenous lymphokines to cultures increases responses to anti-mu and SAC. Addition of indomethacin to cultures greatly increases the SAC response and causes a smaller increase in the pokeweed mitogen (PWM) response. When both exogenous lymphokines and indomethacin are present in cultures, responses of patients' cells to all three mitogens are positively correlated with the percentage of CD4+ T cells and negatively correlated with the percentage of CD8+ T cells. Responses to anti-mu and SAC are also positively correlated with the percentage of B cells in these cultures. On the basis of these correlations between B-cell responses and lymphocyte subset frequency, patients' B-cell responses can be mathematically corrected to estimate the responsiveness of the B cells in the presence of normal numbers of CD4+ and CD8+ cells. These corrected responses for all three mitogens are virtually identical to control responses. Furthermore, responses of enriched B-cell populations from HIV+ subjects and normal controls to SAC were not significantly different when assays were performed in the presence of indomethacin and exogenous lymphokines. These results suggest that B cells from HIV+ patients are inherently normal in their responsiveness to B-cell mitogens. The depressed function is imposed upon them as a result of the abnormal frequency of lymphocyte subsets in the blood, by increased prostaglandin production, and deficient lymphokine production. PMID- 1760233 TI - [Rehabilitation of patients following brain injuries: specialized institution or general rehab center?]. AB - The capacity for the rehabilitation of patients who have been affected by a brain injury does not meet the needs. Additional capacities are to be created in Switzerland. It is discussed whether it is preferable to create specialised institutions for the rehabilitation of the brain injured patient or whether these patients should rather be admitted to general rehabilitation centers. The advantages and disadvantages of these two options are discussed. The advantages of the admission of brain injured patients to general rehabilitation centers is stressed and the demand for special strategies and staff is described. PMID- 1760234 TI - [Facial injuries in bicyclists: epidemiological analysis and prophylactic consequences]. AB - Bicycle accidents in adults are common and concern frequently injuries to head and face. 150 of totally 216 patients with cycle accidents in a six month' prospective study at the Basel University Hospital showed face and head trauma. 85 severe facial injuries treated operatively by the Clinic for Reconstructive Surgery between 1985 and 1989 are analysed in detail. These facial injuries are rarely life threatening and normally the postoperative outcome is good. Nevertheless, usual bicycle helmets cannot avoid facial trauma. Therefore traffic educational programs are the most important prophylactic efforts. Technical progress and improvement of the bicycles ask for better trained cyclists. Further more, the importance of really respecting the traffic rules as well as the construction of separate cycle routes is stressed. PMID- 1760235 TI - [Simplification of osteosynthesis procedures of the hand bones using newly developed mini-osteosynthesis]. AB - From unsatisfactory results in fractures in the hand treated with K-wires or other osteosynthesis we felt the need to develop new material for osteosynthesis. Our goal was to simplify the operative procedure, to enable exact anatomical reposition to avoid or reduce splinting in order to prevent adhesions and secondary operations. Further more to be able to reduce and stabilise small fragments. After more than 4 years of experience with our material in more than 200 osteosynthesis we can conclude, that our goal has been accomplished to a great deal. We would like to present this procedure. PMID- 1760236 TI - [The treatment of fresh and chronic scapho-lunate tendon ruptures using trans osseous reinsertion and capsulodesis]. AB - Presented here is a surgical method which attempts to reconstruct the dorsal scapho-lunate ligaments in a anatomical manner. This is done by using the remainders of the ligaments which, in our patients, where still present month after the accident. For additional stabilisation a capsulodesis according to Blatt is performed. The early results up to 20 month after surgery in 11 patients are encouraging, especially according to subjective complaints. However, a restriction of movement must be expected. The dorsal subluxation of the lunate can only rarely be fully corrected. The more significant long-term results are as yet not available. PMID- 1760237 TI - [Emergency screw osteosynthesis of femoral neck fractures]. AB - 27 patients with femoral neck fractures have been treated by ORIF with 3 or 4 large cancellous bone screws. The operation has been performed as an emergency intervention within 5 1/2 hours after accident. Anterior arthrotomy in direction of the long axis of the neck for evacuation of the intraarticular hematoma has been performed as a routine. Personal follow-up with X-ray documentation after 18 to 106 months (mean 29.5 months) showed complete rehabilitation in 22 patients and 2 femoral head necroses (7.4%). We conclude that these good results are due to the short interval between accident and operation as well as to the evacuation of the intraarticular hematoma, together with a stable internal fixation and functional rehabilitation. PMID- 1760238 TI - [The treatment of fresh Lisfranc dislocations and fracture-dislocations]. AB - Dislocations and fracture dislocations of the tarsometatarsal joint are usually the result of a high energy trauma to the forefoot. A missed diagnosis or an insufficient treatment or a massive destruction of the tarsometatarsal joint result in a high rate of late morbidity. An appropriate radiological assessment, open anatomical reduction and temporary K-wire arthrodesis followed by a functional after-treatment can improve the long-term results of this severe forefoot injuries. The long term results (7 months to 20 years) of 24 tarsometatarsal injuries are analysed and a concept of their treatment presented. PMID- 1760239 TI - [Role of arthroscopy in complex sports injuries]. AB - Shoulder lesions caused by accident are often of complex nature. In most cases, different structures are involved, which cannot be distinguished and individualized clinically with certainty. Arthroscopy permits far more differentiated diagnosis with systematic revision of traumatized structures. Besides the possibility of comprehensive repair (e.g. in part arthroscopic, in part open), the faster rehabilitation attained by minimal exposures is also of importance. PMID- 1760240 TI - [Comparative microstructural studies on collagen and elastic fiber systems of the cruciate ligaments]. AB - The aim of the present study was to compare the collagenous fibre systems of the anterior (ACL) with the posterior cruciate ligament (PCL). 22 cruciate ligaments were examined by the combined use of light-, transmission- and scanning electron microscopy. Characteristic interligamental differences were established. ACL: more anchoring type VI collagen, thinner but more branched fibrils, complex collagen networks, much more elastic elements. PCL: more type IV collagen, many intrinsic vessels, thicker fibrils, parallel fibre arrangement. The results indicate that the ACL is exposed at the first line to rotational forces, the PCL probably more to tensional forces. The collagen fibre arrangement of the cruciate ligaments is to take into consideration by the surgeon. PMID- 1760241 TI - [Prevot's method of elastic-stable endomedullary fixation--an ideal method for the management of juvenile shaft fractures]. AB - We report on the experiences on the internal fixations of long bones which has replaced the non operative method of extension over the last years in our clinic. Although the short-term results of the internal fixations are very convincing the follow-up of these patients will give us further informations on its validity. The well defined aim is to find the treatment with the best chance of restitution combined with the lowest risk-rate. PMID- 1760242 TI - [The importance of ADP for medical statistics]. AB - Recent german articles concerning medical statistics give priority to data acquisition. This contribution describe the statistical analysis and presentation of the results of the Swiss accident insurance Company (SUVA) with 1.9 million of insured workers. This documentation covers per year approximately 450,000 accidents at work and in free time. The documentation include primarily the insurance-data, for medical purposes we use the adjacent diagnoses (up to 20 per accident). The new medical statistic (SUMEST) begins with the accidents of the year 1984, updated until 1988, this means, that we have a statistic of the outcome of accidents. For the analysis we use properties of the personality, details of what happened, injury, expenses for healing and results. The primary presentation is a collection of tables for every diagnosis (total 417) with the most important criteria for the cases. It is provided to publish results of special problems like time of disability, influence of algodystrophy etc. The possibility to analyse a big documentation (25 MBytes) with a personal computer give to the physician the possibility to perform the statistical analysis himself and to select the significant results immediately. PMID- 1760243 TI - Chromosome 11q13 abnormalities in human cancer. AB - Structural abnormalities affecting band q13 of chromosome 11 have been reported in a variety of human tumors, particularly multiple endocrine neoplasia type 1 (MEN1), certain low-grade B-cell neoplasms, and a significant subset of breast and squamous cell carcinomas. The perturbations of the region are also varied, ranging from allele loss and deletions to specific translocations and DNA amplification. Given their clinical relevance in classifying tumors and identifying patients at increased risk, it is important to locate and characterize the genes on which these aberrations impinge. Here we assess the candidate genes identified thus far and the evidence that implicates them in tumorigenesis. PMID- 1760244 TI - Gene-specific repair of DNA damage induced by UV irradiation and cancer chemotherapeutics. AB - DNA repair processes are critically important in the prevention of carcinogenesis, and currently much research is directed toward elucidation of the biochemical mechanisms by which DNA repair occurs. Techniques have been developed for examining individual genes to quantitate the lesions induced by various chemotherapeutic agents and to measure the rate of gene-specific DNA repair. In mammalian cells, the DNA repair response exhibits intragenomic heterogeneity active genes are preferentially repaired and the transcribed strand of DNA is repaired more rapidly than the nontranscribed strand. These studies have provided new insight into the molecular biology of DNA repair and a new perspective on the role of repair processes in cellular resistance to DNA damage and malignancy. Elucidation of the mechanisms by which gene-specific lesions are formed and repaired will be important if we are to understand the fundamental processes of malignancy. PMID- 1760245 TI - Photodynamic therapy of malignant tumors--recent developments. AB - Photodynamic therapy (PDT) is a promising new cancer treatment modality in which tumor cells are killed as a result of photoactivation of a tumor-localizing photosensitizing agent. Since activating light can be targeted specifically to tumors, and tumor-selective photosensitizing agents are being developed, this treatment has the potential to induce highly selective destruction of malignant cells. To date, PDT has been applied to a large variety of human carcinomas, resulting in successful eradication of single tumor nodules and several types of superficial tumors. Current research is aimed at improving the efficacy and tumor selectivity and tumor destruction. The most immediate benefits of PDT are likely to be seen in patients treated with a combination of this and other forms of therapy. PMID- 1760246 TI - All about B cells. PMID- 1760247 TI - Radioprotection with cytokines: a clarification of terminology. PMID- 1760248 TI - Serum-free growth and karyotype analyses of cultured normal and tumorous (SqCC/Y1) human buccal epithelial cells. AB - Epithelial cell cultures were obtained following tryptic digestion of normal human buccal mucosa. Primary cultures exhibited markedly higher colony-forming efficiencies and growth rates using fibronectin/collagen-coated, as compared to non-coated culture dishes and a serum-free MCDB 153 medium developed for epidermal epithelial cells than a similar medium previously developed for buccal explant outgrowth cultures. At the preferred conditions, the cells could be transferred at least 5-fold, divided at about one population doubling per day, and commonly underwent 60 population doublings resulting in yields of 10(8) to 10(11) cells per cm2 mucosal specimen. Moreover, these conditions successfully cultivated a buccal carcinoma cell line (SqCC/Y1) for several months. The carcinoma cells were resistant to factors that inhibited growth or induced differentiation of normal cells, i.e., transforming growth factor type beta 1, Ca2+, or serum. Karyotype analyses of SqCC/Y1 cells showed 63 to 83 chromosomes per metaphase and consistent occurrences of monosomy 1, tetrasomy 19 and 20, as well as trisomy 22, and at least 7 marker chromosomes, whereas cells obtained from non-cancerous donors were diploid. It is concluded that the similarly defined culture conditions may now be applied to study characteristics of both normal and tumorous buccal epithelial cells. PMID- 1760249 TI - Cell-cycle associated transcriptional regulation of ribonucleotide reductase in L1210 leukemia cells and drug-resistant variants. AB - Previous studies from this laboratory have shown that the steady-state levels of the mRNA for the non-heme iron (NHI) subunit of ribonucleotide reductase were markedly elevated in hydroxyurea-resistant L1210 cell lines with minimal changes in the mRNA levels for the effector-binding (EB) subunit. In the present study, wild-type L1210 cells and their drug-resistant variants [hydroxyurea-resistant (HU-7); deoxyadenosine-resistant (Y-8); and deoxyadenosine/pyrazoloimidazole resistant (ED2)] were synchronized by EGTA treatment in the G0/G1-phase of the cell cycle. Upon the addition of CaCl2, the cells reentered the cell cycle. The steady-state levels and the transcriptional rates of the mRNAs for the EB subunit and glyceraldehyde-3-phosphate dehydrogenase were measured and found to be similar in the drug-resistant variants compared to the wild-type cells. While the steady-state level of the mRNA for the NHI subunit was increased 35-fold in the HU-7 cell line, the transcription rate was increased only 7-fold. The increase in the transcription rate did not account for the large increase in the steady-state level. These data indicate that the increased steady-state level of the mRNA for the NHI subunit in the HU-7 L1210 cell line was not due to cell-cycle differences and that post-transcriptional processing and/or stability may play a role as well. PMID- 1760250 TI - Cytotoxicity and DNA crosslinks produced by mitomycin analogs in aerobic and hypoxic EMT6 cells. AB - Several mitomycin antibiotics were evaluated for their capacities to kill EMT6 tumor cells and to produce DNA crosslinks under conditions of oxygenation and hypoxia. The agents examined included mitomycin C, porfiromycin, and the 7 aminomethyl dithioacetal derivative of mitomycin C (BMY-43324), all of which caused greater kill of hypoxic cells than of their oxygenated counterparts; the N,N'-dimethylaminomethylene derivative of mitomycin C (BMY-25282), which was considerably more cytotoxic under oxygenated conditions than in hypoxia; and the N,N'-dimethylaminomethylene derivative of porfiromycin (BL-6783), which was equal in its toxicity to hypoxic and oxygenated cells. All of these agents produced DNA crosslinks in EMT6 cells, as measured by alkaline elution. The number of crosslinks required to produce a given amount of cell kill was similar, regardless of the mitomycin employed or the degree of oxygenation, suggesting that the crosslinking of DNA was a major lesion in the cytodestructive action of the mitomycins. PMID- 1760251 TI - Intracellular mechanisms involved in leukotriene C4-stimulated adhesion of U-937 cells. AB - Leukotrienes C4 and D4 (LTC4 and LTD4) stimulated, 5- to 6-fold, the adhesion of the monoblastoid cell line U-937 to plastic. Half-maximal effects were observed around 1 nM. Leukotrienes E4 and B4 (LTE4 and LTB4) were less effective. The adhesive response to LTC4 was inhibited by pertussis toxin and was completely dependent on the presence of extracellular Ca2+. The LTC4-stimulated increases in inositol-phosphates and in intracellular Ca(2+)-concentration were insensitive to pertussis toxin. Activation of leukocyte adhesion is a novel action of cysteinyl leukotrienes and the present study suggests that control of U-937-cell adhesion by LTC4 involves two pathways; one pertussis toxin insensitive pathway regulating intracellular Ca2+ in a manner partly dependent on extracellular Ca2+ and one pertussis toxin sensitive pathway not concerned with Cai(2+)-regulation. PMID- 1760252 TI - Effects of homo- and heterodimeric isoforms of PDGF on signalling events in rat renal mesangial cells. AB - Platelet-derived growth factor (PDGF) exists in three dimeric isoforms, AA, BB and AB. Mesangial cells exclusively bound the BB homodimer and responded only to the BB isoform in terms of DNA synthesis and phosphoinositide hydrolysis. PDGF-BB stimulated a dose-dependent formation of inositol trisphosphate (InsP3). Neither pertussis toxin nor short-term (10 min) treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited the PDGF-BB-evoked production of InsP3. In contrast, the response to PDGF-BB was attenuated in cells in which protein kinase C has been down-regulated by long-term (24 h) treatment with TPA. In parallel to the generation of InsP3, there was a biphasic increase in 1,2-diacylglycerol (DAG). The second peak of DAG generation was associated with a concomitant 2-fold increase in choline formation. In addition, PDGF-BB stimulated the accumulation of phosphatidylpropanol, produced by phospholipase D phosphatidyl transferase activity, when 1-propanol was added to mesangial cells. Stimulation of mesangial cells with PDGF-BB caused a dose-dependent formation of prostaglandin E2. Furthermore, mesangial cells secreted PDGF-AA into the culture supernatant. PMID- 1760253 TI - Evidence that metabolically active synaptosomes lack functional cyclic AMP dependent protein kinase. AB - Cyclic adenosine monophosphate (cAMP)-mediated signal transduction was evaluated in synaptosomes prepared from rat brain cortex. Adenylate cyclase was responsive to known adenylate cyclase stimulators including peptides (CRH and VIP), catecholamines (norepinephrine and isoproterenol) and ligands that directly stimulate adenylate cyclase (forskolin). Cyclic AMP accumulation also increased approximately 2 to 3-fold, but none of the agonists was able significantly to activate cyclic AMP-dependent protein kinase (A-kinase) in cortical synaptosomes. However, in parallel studies with slices prepared from rat brain cortex, adenylate cyclase activity, cAMP accumulation and A-kinase activity were all stimulated by CRH, VIP, norepinephrine, isoproterenol and forskolin. These data suggest that, in intact synaptosomes, either the cellular machinery which facilitates binding of cAMP to the regulatory subunit of A-kinase is missing or the cAMP produced by adenylate cyclase is not accessible to A-kinase. PMID- 1760254 TI - The proteolysis of membrane-associated protein kinase C as a possible component of the signalling pathway leading to c-myc induction in B lymphocytes. AB - Occupancy of surface immunoglobulin (sIg) receptor for antigen expressed on resting B cells initiates increased turnover of membrane-associated phosphatidylinositol (PI), which ultimately leads to the enhanced expression of c myc mRNA. The mechanism which links these initial membrane biochemical changes to subsequent alterations in c-myc transcription is unclear. The present study examines the possible involvement of PKC and its calpain-generated proteolytic fragment, protein kinase M (PKM), in conveying the membrane-associated signal to the nucleus. Utilizing an in vitro phosphorylation assay, we have shown that a calcium-dependent protease, similar to calpain, is involved in the downregulation of membrane-associated PKC induced by anti-immunoglobulin or phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation of resting B cells. In addition, we have confirmed previous studies showing that PMA and ionomycin are both required for optimal expression of c-myc mRNA. The enhanced expression of c-myc mRNA is sensitive to inhibitors of PKC, such as H-7 and sangavimycin, providing evidence for a prominent role of PKC and/or PKM in the receptor-mediated up-regulation of c-myc message expression. Finally, a calpain inhibitor interferes with the transmission of the membrane-associated signal which induces the increased expression of c-myc mRNA. Our results are consistent with the hypothesis that the calpain-mediated proteolysis of membrane-associated PKC is involved in the sIg mediated signal transduction pathway. PMID- 1760256 TI - [The origin of malformations]. PMID- 1760255 TI - Distribution of arrestin-like protein and beta-subunit of GTP-binding proteins in quail choroid plexuses. AB - Monoclonal antibodies (Mabs) directed against retinal arrestin (S-antigen) were used to detect and characterize this protein in choroid plexus (CP) of quails maintained during eight days, either under long-day photoperiods or in constant darkness. Immunocytochemistry and Western blotting confirmed the presence and the distribution of an arrestin-like protein in quail CP. Arrestin-like immunoreactivities in CP were compared with those obtained with Mabs to beta 36 subunit of G proteins (G beta), alpha-subunit of transducin and rhodopsin. Rhodopsin-like and transducin-like proteins could not be detected in choroidal cells, whereas intense positive reactions were observed with anti-G beta and anti arrestin Mabs. The strongest immunoreactivities were found in choroidal ependymocytes of the lateral and IIIrd ventricles. In CP epithelial cells lining the IVth ventricle, very weak or no immunoreactivity could be detected with Mabs to arrestin, while Mab against G beta subunit always provided a positive reaction. In quails maintained in constant darkness, arrestin- and G beta immunoreactivities of CP epithelial cells displayed changes in cellular distribution and intensity (decrease or disappearance of the immunoreactions). The strong arrestin-like immunoreaction located in the apical region of ependymocytes suggests the preferential association of the protein with choroidal microvilli and a possible role in cerebrospinal fluid production assumed by CP cells. PMID- 1760257 TI - [The indications, technics and results of the use of tissue expanders in pediatric surgery]. AB - We review our experience in tissue expansion in twenty-four pediatric patients. The most frequent indications for the use of tissue expanders included congenital nevi and burn scars, they were also used with success in alopecia, congenital abdominal wall defects, mammary hypoplasia and microtia. Tissue expanders were always placed subcutaneously. Both, surgery and body deformity during expansion, were well tolerated. We found complications in five cases, but only in one patient treatment was interrupted. Results were considered excellent in nineteen cases. PMID- 1760258 TI - [Otological assessment in patients operated on for cleft palate]. AB - Tympanometry and otoscopy has been carried out to determine the presence of middle ear disease on patients with cleft palate and the influence of corrective surgery. This explorations have been evaluated preoperatively and at one and six months postoperative follow-up. There is a high incidence of otitis media with effusion in patients with cleft palate, almost 60 per 100 in our study. The influence of cleft palate surgery repair has not revealed as a mayor factor on its resolution, although a visible benefit has been observed in the long term controls. We recommend a otorhinolaryngological follow-up in these patients. PMID- 1760259 TI - [Hepatic artery thrombosis in the pediatric liver transplant]. AB - The hepatic artery thrombosis (HAT) is the most serious complication after pediatric liver transplantation. Most of the cases will need a retransplantation. Multiple factors are keeping in discussion as causes of this complication: Rejection, two or more arteries, complex vascular reconstruction, etc. This article describes our experience with this complication and the prophylactic treatment. From January 1986 through April 1991, 62 orthotopic liver transplants were performed on 48 pediatric patients with a mean age of seven years. The incidence of hepatic artery thrombosis was 19 per 100, increasing when recipients were less than three years and less than 15 kg (23.8 per 100). Forty six cases were rearterialized with end-to-end anastomoses, ten were rearterialized by directly anastomosing them to the recipient aorta and six with iliac artery graft. We use in the last 38 consecutive patients prophylactic heparin during two weeks after transplantation (300 u/kg/d) following with antiaggregants. There were eleven patients with hepatic artery thrombosis, one of them had two episodes in both grafts. We perform a retransplantation in eight patients, two died waiting a new graft and one exceptional patient is out of the clinic with normal liver function and without regraft. Seventeen grafts had two or more arteries from aorta, ten with branches from superior mesenteric artery and five from gastric artery. One graft had a triple hepatic artery and another one was a common hepatic artery from superior mesenteric artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760260 TI - [The surgical treatment of anterior hypospadias. Apropos 590 cases (1966-1988). The indications and results. The current trends in surgical treatment]. AB - The surgical treatment of hypospadias is very complex. The objective is to obtain a satisfactory urinary and genital function with an equal morphological, anatomical and aesthetic result. Our contribution covers twenty-two years of surgical multicentre experience (590 cases). We evaluate the surgical indication, results, complications, associated malformations and study protocols. We have objectively evaluated the evolution of the indications, as well as the application of different techniques depending on the extent of urethral malformation. PMID- 1760261 TI - [Urologic obstructions due to fungal balls]. AB - Fungal urologic infections are unusual in children. They are associated with chronic uropathies, citostatics and antibiotic treatments and depressed immunity which allow the pathologic growth of a saprofitie organism. This infection must present special forms when the mycotic development is realized in cavities and special advantageous conditions. Then it adopt the form of fungal bezoars, and it can mobilize itself and provoke obstructions in the urinary tract. We present two cases of urinary obstructions secondary to fugal bezoars. The obstruction was localized in the uretero-vesical junction. In both of them the infection was associated with long antibiotic treatment, and with severe immunodeficiency only in one. The diagnosis was possible by echography and direct determination of candida albicans in urine. We proved also temporary ureterovesical stenosis we found before a reflux. The treatment included intravenous and local anfotericine B with dissolution of the bezoar in three and four days respectively. PMID- 1760262 TI - [Fetal urinary dilatation due to vesico-ureteral reflux]. AB - We have retrospectively studied 163 newborns referred to us between 1986 and 1990 for sonographic diagnosis of intra-uterine upper urinary tract enlargement. All were studied by paediatric radiologists on days 5th or 6th after birth by means of sonography and voiding cystourethrogram (VCU). Fifty percent had also IVP. No urinary tract disease could be found in 44 children, obstructive uropathy or cystic disease were diagnosed in 58 children and 61 patients had vesico-ureteric reflux (VUR). They form the basis of the present report. There was a male-to female ratio of 3.3 to 1. Neonatal ultrasonography was normal in 11 cases, 42 had pyelectasia (bilateral in eight cases) and eight had ureterohydronephrosis (bilateral in seven). VUR was bilateral in 28 cases, right in 16 and left in 17. Out of the 89 refluxing units, VUR grade was I in 11, II in 16, III in 24, IV in 14 and V in 23. There was intra-renal reflux in 17 units. Some other form of urinary tract disease was detected in 29 babies (47.5 per 100). Twenty-eight patients were operated upon and the remaining are under long-term urinary antisepsis with only five episodes of infection. The considerable proportion of false negatives for VUR in neonatal ultrasonography (30 per 100) and the high grade of some of these cases lead us to strongly advise routine VCU for patients with intra-uterine urinary tract dilatation. PMID- 1760263 TI - [An analysis of the introduction of pediatric surgery in Spain]. AB - The specialty of paediatric surgery (P.S.) has been officially recognized in Spain since 1977 as being independent of other surgical areas, and charged with carrying out pathological surgery in paediatric ages. In spite of the considerable progress made, it suffers constant threats, which is why we feel it is opportune to review various aspects of the problems it is currently facing. If we observe how the specialty is distributed, we can see that there are many paediatric services and professorships which do not send their patients to a P.S. specialist. The child's health may suffer as a result of the Administration's decision to allow twenty-two provinces (seven million inhabitants) to go without P.S. We know that many specialties carry out surgery on the paediatric population, so we may well ask: What use is the P.S. qualification? Information was collected from legal sources which indicates the need to hold the qualification of "homologated specialist", given that "the doctor who ventures into specialties which are not his/her own may add a risk factor, and thereby give rise more easily to an offence of negligence". It is time that concepts and competences of the specialty were clarified, and to fight to ensure that all Spanish children should be operated on by legally qualified specialists. PMID- 1760264 TI - [Continuous arteriovenous hemofiltration in the newborn surgical patient]. AB - Continuous arteriovenous hemofiltration is an extracorporeal technique that uses the arterio-venous pressure gradient to remove plasma water and solutes via convection through a hemofilter. This therapy is specially indicated in the newborn with acute renal failure, hypervolemia and/or metabolic disturbances. The technique has good clinical tolerance in the critically ill patient because of little hemodynamic repercussion without major osmolar shifts, low anticoagulation needed and its simplicity (no need for specialized staff). PMID- 1760265 TI - [Ectopic gastric mucosa in the proximal esophagus]. AB - Gastric mucosa is not found often in the proximal and medial esophagus. Hematemesis and dysphagia are the most frequent symptoms. We report a six year old child who complained of difficulty in swallowing. A filling defect was detect in the esophagogram. We biopsied the suspected area, through an endoscopy and the pathological examination informed of ectopic gastric mucosa. We performed a 99Tc isotopic study. The child is on ambulatory controls and at the moment is asymptomatic. PMID- 1760266 TI - [A case of total intestinal aganglionosis. 2 years of survival]. AB - A two-year-old male is presented. Small bowel aganglionosis was proved to extend to 3 cm below ligament of Treitz. Gastrostomy and ileostomy was done. He received his caloric intake by cyclic home parenteral nutrition trough implantable venous system. At eighteen months of age, intestinal transplantation was refused and reoperation was done. The child underwent Ziegler's miotomymiectomy on 60 cm of aganglionic jejunum. Now at twenty seven months of age he receives cyclic parenteral nutrition, and enteral feedings are being increased slowly. The weight/height was at 91 per 100 standard, intestinal motility appears much better on contrast study and he is developmentally a normal child. PMID- 1760268 TI - Nursing development units: a new hand on the tiller. Interview by Charlotte Alderman. PMID- 1760267 TI - Update on AIDS. PMID- 1760269 TI - Health visiting: working in a divided community. PMID- 1760270 TI - Health care assistants: open College? PMID- 1760271 TI - Audit commission: lean, mean quality care. PMID- 1760272 TI - Computer records in occupational health. PMID- 1760274 TI - The extended role of the nurse: a review. PMID- 1760273 TI - Psychotherapy: therapeutic use of metaphor. PMID- 1760275 TI - Continuing education: community education and practice. PMID- 1760276 TI - Nursing: yin and yang. PMID- 1760277 TI - Tradimus. Accommodation: living-in fear. PMID- 1760279 TI - Tradimus. Mental health nursing: RMNs need counselling. PMID- 1760278 TI - Tradimus. Ethics: getting a moral body. PMID- 1760280 TI - Tradimus. Health education: not enough cooks? PMID- 1760281 TI - Tradimus. Education: degree to disagree. PMID- 1760282 TI - Tradimus. International: New York, new work. PMID- 1760283 TI - Tradimus. Bereavement support: Students are human, too. PMID- 1760285 TI - The Clay column. PMID- 1760284 TI - Tradimus. Grieving: confronting death. PMID- 1760286 TI - The image of nurses: the times they are a'changing? PMID- 1760287 TI - Education. Doctors and nurses: a personal view. PMID- 1760288 TI - Personnel: NHS Trusts and equal opportunities. PMID- 1760289 TI - Post-traumatic stress management. PMID- 1760290 TI - Nursing issues in intravenous therapy. PMID- 1760292 TI - Ear, nose and throat nursing: aural hygiene and the use of cotton swabs. PMID- 1760291 TI - Uncommon disorders. Malignant hyperpyrexia. PMID- 1760293 TI - Pros and cons of working as a bank nurse. PMID- 1760294 TI - Scare tactics don't work. Interview by Audrey Thompson. PMID- 1760295 TI - Lateral nursing: the Pink revolution. PMID- 1760296 TI - AIDS focus. Groups for people with HIV/AIDS. PMID- 1760297 TI - AIDS focus. Sexuality, saints and sinners. PMID- 1760298 TI - AIDS focus. The challenge of the nineties. PMID- 1760299 TI - Quality Assurance Network Newsletter. Hooked on quality. PMID- 1760300 TI - Quality Assurance Nursing Newsletter. PMID- 1760301 TI - Quality Assurance Network Newsletter. A cycle of quality. PMID- 1760302 TI - Quality Assurance Network Newsletter. Hands-on quality. PMID- 1760303 TI - Politics. Waldegrave on nursing. Interview by Norah Casey. PMID- 1760304 TI - The A-Z Christmas survival guide. PMID- 1760305 TI - Homelessness: Christmas in the open air. PMID- 1760306 TI - Linking poverty and ill health. PMID- 1760307 TI - Continuing education: developing a career through nursing. PMID- 1760308 TI - Staff development. Clinical grading: the silver lining? PMID- 1760310 TI - On being treated as an ignorant hillbilly when escorting a patient to a London hospital. PMID- 1760309 TI - Paediatric intensive care: transposition of the great arteries. PMID- 1760311 TI - Substance abuse: Christmas cheer or drear? PMID- 1760312 TI - Dreams come true in '92? PMID- 1760313 TI - Ethnic issues: from plasters to poverty. PMID- 1760314 TI - Statutory bodies: proposals for major change. PMID- 1760315 TI - Family interventions in schizophrenia. PMID- 1760316 TI - Midwifery: an exercise in pregnancy. Interview by Charlotte Alderman. PMID- 1760317 TI - Neurology: relating pathology to hand preference. PMID- 1760318 TI - Uncommon disorders. Epidermolysis bullosa. PMID- 1760319 TI - Continuing education and UK nurses. PMID- 1760320 TI - Breastfeeding shame? PMID- 1760321 TI - Communication: of verbosity and verbiage. PMID- 1760323 TI - Cardiology update. Transplant assessment. PMID- 1760322 TI - Cardiology update. No smoke without fire. PMID- 1760324 TI - Cardiology update. Surgical aspects of heart transplantation. PMID- 1760325 TI - Cardiology update. Endomyocardial biopsy technique. PMID- 1760326 TI - Cardiology update. Thoracic sympathectomy for angina. PMID- 1760327 TI - Cardiology update. Dorothy: a breath of fresh air. PMID- 1760328 TI - Education: No More Nightingales. PMID- 1760330 TI - Special hospitals: a better understanding. Interview by Derek Hand. PMID- 1760329 TI - Old age is not a reason to fall. PMID- 1760331 TI - Continence training programmes: need for standardisation. PMID- 1760332 TI - Continuing education: application of CATS in the health service. PMID- 1760333 TI - Reviewing trends in nurses' earnings. PMID- 1760334 TI - Manipulative and splitting behaviours. PMID- 1760335 TI - Developing an NDU: the manager's role. PMID- 1760336 TI - Pleasures of returning to the profession. PMID- 1760337 TI - Neat work on networks. PMID- 1760338 TI - Managing to take the lead. PMID- 1760339 TI - No masters without slaves. PMID- 1760340 TI - Health promotion: no smoke without ire. PMID- 1760341 TI - Community nursing: visitations on the elderly. PMID- 1760342 TI - Learning disabilities: qualified in caring. PMID- 1760343 TI - General election: a passion for politics. PMID- 1760344 TI - Northern Ireland. 'It's the patients who take us through.'. PMID- 1760345 TI - Continuing education in an NDU. PMID- 1760346 TI - Sports therapy in mental illness. PMID- 1760347 TI - Management of fungal infections. PMID- 1760348 TI - Downgrading of arts-centered education in state schools. PMID- 1760350 TI - The Nat Health files. Welcome to Glandstand. PMID- 1760349 TI - There's no Seventh Cavalry. PMID- 1760351 TI - John Kelly: an extraordinary man. Interview by Alex Mathieson. PMID- 1760352 TI - Car tax: steering through taxation. PMID- 1760353 TI - A day in the life ... a nurse of ill repute. PMID- 1760354 TI - Essential fatty acids and the skin. PMID- 1760355 TI - In-situ hybridization using digoxigenin-labelled probes in human skin. AB - This study demonstrated that in-situ hybridization using digoxigenin-labelled oligonucleotide poly-T probes and digoxigenin-labelled riboprobes for keratin 14 is possible on routinely fixed paraffin-embedded sections. The resolution and time course of the detection system compared favourably with isotopically labelled probes. Major differences were shown in keratinocyte messenger RNA content with differentiating cells expressing high levels when compared with the basal layers. Previous work on the distribution of keratin 14 messenger RNA was confirmed and we were able to show that using non-isotopic in-situ hybridization, sensitive and accurate cellular localization was feasible in skin sections. PMID- 1760356 TI - The expression of MHC class II (Ia) antigens on mouse keratinocytes following epicutaneous application of contact sensitizers and irritants. AB - The expression of MHC class II (Ia) antigens on mouse keratinocytes was studied following both the induction and elicitation of contact sensitivity, and after primary irritant reactions. IA+ and IE+ keratinocytes were detected, using an indirect immunofluorescence assay on epidermal sheets, only after the induction and elicitation of contact sensitivity with the sensitizers oxazalone, picryl chloride and 2,4-dinitrochlorobenzene but not with formaldehyde. Ia+ keratinocytes were not detected after epicutaneous application of the non sensitizing irritants croton oil, SDS and anthralin, or following attempted sensitization of nude mice, suggesting that the expression of Ia antigen on keratinocytes during contact sensitivity reactions is T-cell mediated. Because Ia antigen expression on keratinocytes could be detected only several days after induction or elicitation of contact sensitivity, and contact sensitization could also be demonstrated to occur independently of aberrant Ia expression, Ia+ keratinocytes cannot be involved in the initiation of these reactions. However, they might be important in exerting an immunomodulatory influence during the later stages of the responses to certain sensitizers. PMID- 1760357 TI - Profile of prostanoid release following antigen challenge in vivo in the skin of man. AB - We have previously characterized the kinetics of prostaglandin D2 (PGD2) production at cutaneous sites of allergic inflammation employing a blister chamber model. In this study, a more complete profile of prostaglandins released in vivo was obtained. PGD2 release, as measured by radioimmunoassay and by combined gas chromatography-mass spectrometry, was evident within 1 h after antigen challenge with maximal levels occurring 3-4 h post-challenge. The 11 ketoreductase metabolite of PGD2, 9 alpha, 11 beta-prostaglandin F2 was present in blister fluid from three of six patients at the time of maximal levels of PGD2. The stable non-enzymatic hydrolysis product of prostacyclin, 6-keto prostaglandin F1 alpha, was significantly elevated in blister fluid from five of six patients following antigen challenge. In these subjects, the levels of 6 kappa-PGF1 alpha were highest in samples obtained 1 and 2 h after antigen challenge and remained significantly elevated until 5 h post-challenge. Levels of prostaglandin E2, prostaglandin F2 alpha and thromboxane B2 did not vary significantly. These studies suggest that following antigen challenge two fatty acid cyclo-oxygenase products of arachidonic acid are released, PGD2 and prostacyclin. The 11-ketoreductase metabolism of PGD2 to 9 alpha, 11 beta-PGF2 could represent a mechanism by which the biological effects of PGD2 are prolonged in cutaneous tissue. The presence of 6 kappa-PGF1 alpha in the blister fluid suggests that significant prostacyclin release occurs as the result of antigen challenge and could represent a mechanism by which the prolonged microvascular response in cutaneous tissue may occur. PMID- 1760358 TI - Electron microscopic and immunocytochemical studies of the sequence of events in psoriatic plaque formation following tape-stripping. AB - Electron microscopic and immunocytochemical studies were performed on sequential biopsies following the tape-stripping of the uninvolved skin in 12 patients with psoriasis. In the biopsies taken after 5 min for up to 7 days during the pre psoriatic phase, there were initial lymphocyte-Langerhans cell interactions as well as interactions between lymphocytes and keratinocytes. In biopsies taken after 6-8 weeks during the proliferative phase there were lymphocyte-macrophage interactions. In the 24-h and 7-day biopsies there were close contacts between epidermal lymphocytes and keratinocytes via microvilli, with blebbing of the keratinocyte plasma membranes and granular cytoplasmic changes around these microvilli. Few basal keratinocyte herniations were noted during this phase. The 6-8-week biopsies of Kobner-positive patients were characterized by a marked increase in lymphocyte-macrophage interactions via similar microvillous processes with associated electronlucent areas suggestive of cytotoxicity. PMID- 1760359 TI - Three-dimensional ultrastructural study of molluscum contagiosum in the skin using scanning-electron microscopy. AB - The three-dimensional ultrastructure of molluscum contagiosum virus (MCV) in human skin was visualized using scanning-electron microscopy with the osmium dimethyl sulphoxide-osmium method. There were spherical, ellipsoidal, brick shaped, miniature and incomplete forms of MCV. In all the forms the surface had densely distributed small protrusions and all had the same ultrastructure. All the forms had one or two long cord-like substances that appeared to be linked together, but became short, vestigial or absent on the surface of the mature virus. The cord-like substances were connected to the core of the MCV. In the matrix between the viruses, the cord-like substances formed an intricate fine network. PMID- 1760360 TI - The clinical expression of bullous pemphigoid is not determined by the specificity of the target antigen. AB - The major bullous pemphigoid (BP) antigen is a 220-240-kDa polypeptide, although some BP sera recognize bands of 180-200 kDa or lower molecular weight. We have investigated to what extent this heterogeneity of the target antigen accounts for the clinical diversity of BP. Immunoblotting studies against extracts of salt separated epidermis were performed on sera from 39 patients with BP. The blotting patters obtained were correlated with the clinical findings, with particular reference to prodromal itching, lesion morphology and severity, mucosal involvement, presence of milia, dapsone responsiveness and disease duration. The results confirm that the major BP antigen is a 220-kDa polypeptide, and that the 180-kDa polypeptide is a second and sometimes the sole BP antigen identified in immunoblots. Rarely, multiple bands of lower molecular weight were found. There was no correlation between the pattern of BP antigens detected in immunoblots and the clinical presentation and course of BP. There was considerable clinical diversity even among the nine patients showing specificity for a single 220-kDa target antigen. Although two patients with a single 180-kDa antigen specificity had a disease of unusually long duration, factors other than antigen specificity must determine the clinical expression of BP. PMID- 1760361 TI - In-vivo studies of the action spectrum and time course for release of transforming growth factor-alpha by ultraviolet irradiation in man. AB - Transforming growth factor-alpha (TGF-alpha) is a growth-promoting cytokine which enhances epithelial proliferation and is secreted by a wide variety of tumour cells. It is also present in normal human epidermis and its overproduction may be responsible for epidermal hyperproliferation in psoriasis. Ultraviolet (UV) B irradiation of human skin leads to epidermal damage and significant subsequent hyperplasia after approximately 24 h, whereas UVA irradiation has little such effect and predominantly damages the dermis. The relative efficacies of UVB and UVA in releasing TGF-alpha were studied in 10 subjects of skin types I and II using a skin-chamber technique and a specific TGF-alpha radioimmunoassay. Significantly elevated concentrations of immunoreactive TGF-alpha were detected in samples after 24 h in UVB-irradiated compared with unirradiated skin. Samples at earlier time points from UVB- and UVA-exposed skin contained measurable levels of TGF-alpha but these were not significantly elevated above the levels found in samples from unirradiated areas. These results, which suggest the UVB irradiation increases release of TGF-alpha from human skin at 24 h, indicate that TGF-alpha may be implicated in UVB-induced epidermal hyperplasia. PMID- 1760362 TI - UVA solarium versus UVB phototherapy of atopic dermatitis: a paired-comparison study. AB - In a paired-comparison study, 21 patients suffering from atopic dermatitis were treated with fluorescent tubes radiating mainly ultraviolet A (UVA) on one half of the body and with tubes radiating mainly UVB on the other. Treatment was given three times a week for up to 8 weeks. Eight variables reflecting disease status were recorded and the sum of these comprised the total score. The total score and the overall evaluation score were better with UVA therapy (P less than 0.02 and P = 0.01, respectively). No statistically significant difference for the pruritus score was found. The reduction in extent of dermatitis, seen with both therapies, was more pronounced with UVA (P less than 0.05). Differences in the healing score were not statistically significant. Treatment with UVA resulted in healing or considerable improvement in 15 patients and 13 patients showed improvement when treated with UVB. A better result was found with UVA in 10 subjects and with UVB in two subjects. Equal results occurred with both UVA and UVB in nine of the patients although most preferred UVA treatment. PMID- 1760363 TI - Loss of lanolin patch-test positivity. AB - Thirty-seven patients who had shown a relevant positive patch-test response to lanolin within the previous 5 years were retested. Only 41% demonstrated persistence of the positive patch test to lanolin. Analysis according to age, sex, atopic status, interval between patch testings, strength of the original response and the number of concurrent reactions, were not associated with the persistence of the lanolin response. PMID- 1760364 TI - Cyclo-oxygenase products do not participate in the induction of ornithine decarboxylase in human epidermis. AB - Extensive animal data suggest that prostaglandins are involved in the epidermal induction of ornithine decarboxylase (ODC). We undertook this study to investigate their role during induction of hyperproliferation in human skin. Topical indomethacin (Elmetacin) or vehicle only were applied under occlusion on the backs of healthy volunteers. This was followed 1 h later by Sellotape stripping and biopsies were carried out for the estimation of the levels of ODC. There was no significant difference in the level of ODC in the indomethacin treated and control sites. Also, test sites were irradiated with 3 MEDs of UVB, and this was immediately followed by the application of indomethacin or vehicle only on the irradiated sites. After 8 h biopsies were taken and the levels of ODC were again similar in both sites. The data indicate that the cyclo-oxygenase products in human epidermis do not contribute to the induction of ODC. PMID- 1760365 TI - Skin cancer as a cause of death in Denmark. AB - Denmark has a well-established nation-wide registration system for cancer incidence and mortality. In 1984, 2984 new cases of non-melanoma skin cancer were notified to the Danish Cancer Registry and 40 deaths were attributed to this cause. An evaluation and validation of the death certificates indicate that the true number of deaths caused by non-melanoma skin cancer was 18. Basal cell and squamous cell carcinoma accounted for three and 15 of the deaths, respectively. The estimated lethality is 4.3% for squamous cell carcinoma and 0.12% for basal cell carcinoma. PMID- 1760367 TI - Atypical facial porokeratosis of Mibelli. PMID- 1760366 TI - Relapsing polychondritis: autoimmunity to type II collagen and treatment with cyclosporin A. AB - A case of relapsing polychondritis (RPC) with strongly positive antibodies to both native and denatured type II collagen is reported. This is only the second report of the use of cyclosporin A in the treatment of RPC. PMID- 1760368 TI - General practitioners and minor surgery. PMID- 1760369 TI - Rapid healing of ulcerated necrobiosis lipoidica with optimum glycaemic control and seaweed-based dressings. PMID- 1760370 TI - 'Wet-wrap' dressings for the treatment of atopic eczema in children. PMID- 1760371 TI - Sunscreen protection against UVB, UVA and blue light. PMID- 1760372 TI - Enhanced amyloid deposition in Bowen's disease treated with radiotherapy. PMID- 1760373 TI - Familial progressive hyperpigmentation: a family study in China. PMID- 1760374 TI - Cytoplasmic modification of the nuclear lamina during pronuclear-like transformation of mouse blastomere nuclei. AB - During the successive interphases of cleaving mouse embryos the nuclear periphery diminishes its reactivity to anti-lamin A and C antibodies. This developmentally regulated characteristic can be modified by exposure of the blastomere nuclei to metaphase II (M II) oocyte cytoplasm followed by activation. In the current study we define the cytoplasmic conditions necessary for this modification of 8-cell and 16-cell stage nuclei in hybrids obtained by fusion with metaphase II arrested oocytes, oocytes at various time points after parthenogenetic activation, naturally fertilized eggs (zygotes) and interphase 2-cell embryo blastomeres. The intensity of fluorescence obtained with anti-lamins A/C in the blastomere nuclei increases as a result of fusion with freshly activated oocytes or early zygotes (first 3.0-5.5 h in the case of parthenogenetic activation), and not when eggs or 2-cell blastomeres advanced in interphase are used as partners for fusion. This transformation of the A/C lamin pattern is correlated with the ability to promote pronucleus-like growth of blastomere nuclei in hybrids. Blastomere nuclei introduced into M II-arrested oocytes undergo premature chromatin condensation and dissolution of the nuclear lamina. The results are discussed with regard to certain particularities of the first embryonic interphase of the mouse and the potential involvement of nuclear lamins in pronuclear growth. PMID- 1760375 TI - Some thoughts on the language of cognitive research. PMID- 1760376 TI - Chronic effects of high salt intake and conflict stress on blood pressure in primates. A progress report. AB - The effects of combined behavioral stress and high dietary salt on blood pressure were examined in baboons (N = 4) over the course of 1 year. Either high salt diet (240 mEq Na+/day) or conflict stress were administered for 8 to 16 weeks, followed by high salt intake and stress combined. Mean arterial pressure (MAP) increased by 8 mmHg during high dietary salt alone, by 4 mmHg during stress alone, and increased further to 14 mmHg above baseline during combined salt and stress. Control baboons (N = 2) had no change in MAP across 47 weeks. The data indicate additive effects of chronic high dietary salt intake and behavioral stress on blood pressure in non-human primates. PMID- 1760377 TI - Second-order conditioning of the rabbit's nictitating membrane response. Interstimulus interval and frequency of CS-CS pairings. AB - Second-order conditioning of the rabbit's nictitating membrane response (NMR) was investigated when second-order trials (CS1-CS2) were intermixed with first-order trials (CS2-US) from the outset of training. Experiment 1 showed that CR acquisition to CS1 was inversely related to the CS1-CS2 interval but nevertheless extended to an interval of 8,400 ms. Experiment 2 revealed that CR acquisition of CS1 was an inverted-U function of the number of CS1-CS2 trials relative to a fixed number of CS2-US trials. Experiment 3 directly contrasted second-order conditioning with a reinforced serial compound procedure (CS1-CS2-US) and a mixed procedure in which second-order trials were intermixed with the reinforced serial compound. Second-order conditioning was about half the strength of either the reinforced serial compound or the mixed procedure, which were similar. The present results are discussed with respect to the relative strength of excitatory and inhibitory processes in second-order conditioning. PMID- 1760378 TI - Does anxiety or cardiovascular reactivity have a causal role in hypertension? AB - Anxiety, stress, and cardiovascular reactivity (CVR) are variously believed to play a role in sustained hypertension. Although acute anxiety or stress elicits acute pressor responses, there is little support for their significant role in sustained hypertension. Anxiety correlates poorly with CVR, and blood pressure levels and anxiolytics do not sustain blood pressure lowering in subjects with hypertension-associated anxiety. Chronic anxiety disorders tend to be characterized by relatively low blood pressure and prevalence of sustained hypertension. Blood Pressure Regulation in hypertension is normal, and normo- and hypertensives have similar ambulatory blood pressure variability. Laboratory CVR fails to predict variability in natural environments, hyperreactors do not exhibit increased variability in natural environments, and the increased variability and ambulatory reactivity that is "accounted for" by laboratory responses is small. These findings do not support the belief that hypertension is related to a summation of heightened pressor responses over time. Antihypertensives normalize elevated blood pressures but do not alter CVR in the laboratory or variability in natural environments, probably because of a dual central regulation of resting and reactive blood pressures. Psychological stress responses result from selective neuronal activation rather than from generalized sympathetic neural responses or dysregulation. Differences in blood pressure responses during various emotions are only quantitative, with no specificity of sympathoadrenal or emotional responses to stressors. It may be time to regard reactive cardiovascular responses as physiological, rather than as psychological, and to require much stronger evidence to confirm causal roles of anxiety, stress, and reactivity in sustained hypertension. PMID- 1760379 TI - Mental "stress" and hypertension. Evidence from animal and experimental studies. PMID- 1760381 TI - People need people. Perspectives on the meaning and measurement of social support. PMID- 1760380 TI - Personality, stress, smoking, and genetic predisposition as synergistic risk factors for cancer and coronary heart disease. AB - Risk factors for cancer have been found in the past to act synergistically in a number of studies. However, these studies were not always designed to test the hypothesis of synergism, and have sometimes failed to equate for important variables, which might influence the results. The present study tests the hypothesis that psychosocial variables and physical ones (personality/stress, smoking, and genetic predisposition) interact in a synergistic fashion in the causation of lung cancer and coronary heart disease (CHD). PMID- 1760382 TI - Interrupting neural pathways that transduce stressful information into physiological responses. AB - Stressor-stimuli evoke a noradrenergic process in the frontal lobes, the amplitude of which depends on both the individual's experience with the stimulus and his or her genetic background. Novel and noxious stimuli evoke large frontocortical responses and benign ones evoke relatively larger reactions in persons with a family history of cardiovascular disease. Blockade of neural projections from the frontal cortex and amygdala to the brainstem cardiovascular centers will normalize blood-pressure elevations in experimental hypertension and prevent lethal arrhythmias in animals with a myocardial infarction. The anti mortality effect of the cardiac drugs known as beta-blockers is exerted by inhibition of cerebral beta-receptors, not peripheral ones. A new putative neuropeptide, NLX, may have the same desirable cardiovascular effects, but without the side-effects that limit clinical usefulness. The neural regulation of the heart during stress can be detected by a new deterministic measure of low dimensional chaos in heartbeat intervals. In both animals and humans undergoing myocardial infarction, this deterministic measure correctly predicts lethal arrhythmogenesis, minutes to hours prior to the event. Thus an approach combining both brain and heart studies (i.e., "neurocardiology") has led to an understanding of how stressor-stimuli evoke autonomic reactions. This, in turn, has led to new methods in the diagnosis and treatment of cardiovascular disorders. PMID- 1760383 TI - On humility in science. PMID- 1760384 TI - Schizophrenia: static or progressive pathophysiology? PMID- 1760385 TI - Astrocytosis and schizophrenia. PMID- 1760386 TI - Evidence for neurodevelopment disturbances in anterior cingulate cortex of post mortem schizophrenic brain. PMID- 1760387 TI - The age dependencies of MRI abnormalities in schizophrenia suggest early ventricular enlargement but later prominence of cortical atrophy. PMID- 1760388 TI - Cerebral ventricular abnormalities in schizophrenia: evidence of their early origin and stability over time. PMID- 1760389 TI - Progressive and static ventriculomegaly in schizophrenia: clinical and methodological variables. PMID- 1760390 TI - Psychopathology and the question of neurodevelopmental or neurodegenerative disorder. PMID- 1760391 TI - The age of onset of psychosis as a clue to a defect in the cerebral dominance gene. PMID- 1760392 TI - Information-processing anomalies in the early course of schizophrenia and bipolar disorder. PMID- 1760393 TI - Cross-sectional and longitudinal neuropsychological test findings in first episode schizophrenic patients. PMID- 1760394 TI - Neuropsychological deficits in the early course of first episode schizophrenia. PMID- 1760395 TI - Amphetamine response and duration of illness in schizophrenia. PMID- 1760396 TI - Brain volume loss in schizophrenia: when does it occur and is it progressive? PMID- 1760397 TI - Follow up MRI study in first episode schizophrenia. PMID- 1760398 TI - Brain morphological changes in 1st episode cases of schizophrenia: are they progressive? PMID- 1760399 TI - Evidence against progression of in vivo anatomical abnormalities in schizophrenia. PMID- 1760400 TI - T1 and T2 relaxation times in schizophrenia as measured with magnetic resonance imaging. AB - T1 and T2 relaxation times were measured in ten brain regions on the right and left side in a sample of 27 schizophrenic patients and 37 normal controls. The schizophrenic patients showed a prolongation of T2 relaxation time, and to a lesser extent of T1 relaxation time, which was more predominantly localized in the right hemisphere and in gray matter structures. These results may indicate that metabolic, physiological, or neurochemical brain function in schizophrenia is related in some way to a change in tissue fluid in neuronal cell bodies or interstitial gray matter. PMID- 1760401 TI - ROUNDS, a new time-sampling methodology for the quantitative behavioral assessment of schizophrenic withdrawal. Reliability and validity. AB - Negative symptoms in schizophrenia have been the subject of much research interest. However, there has been a need for a way to measure withdrawal behavior quantitatively over time. We have developed a behavioral time-sampling methodology performed by nursing staff on a schizophrenia inpatient unit. Called ROUNDS, it gathers reliable and valid quantitative data about specific withdrawal behaviors such as posture, daytime sleep and levels of social interaction and activity. This paper describes the development of the method, its implementation, the statistical analysis of its reliability and validity, and the degree to which the data can be replicated with different sampling frequencies. We contend that this method can be applied to the analysis of a wide variety of questions about the nature and treatment response of schizophrenic withdrawal in an inpatient setting. PMID- 1760402 TI - Stage-specific transcription of germline IgH C gamma and C alpha regions during human B cell differentiation. AB - Previous studies have suggested that transcription of germline heavy chain constant region (CH) genes in murine B cells may determine the potential of their different CH regions to undergo isotype switch recombination. We have examined the transcriptional activity across the immunoglobulin heavy chain (IgH) locus in human B lineage cells. Transcription of germline C gamma and C alpha was observed in every surface IgM+ or surface IgM+/IgD+ B cell stage cell line and malignancy. In contrast, such transcription could not be detected in pre-B cells and only low levels of C alpha but not C gamma transcription were evident in IgM-secreting plasmablast cells. Transcriptional activity of germline IgH C epsilon was singularly absent at all stages of B cell development. Our results suggest that germline transcription of the C gamma and C alpha regions may be a constitutive feature of the human B cell differentiation program. Because this transcriptional activity is limited primarily to the B cell stage and occurs prior to the actual isotype switch, the induction of C gamma and C alpha transcription may represent preparation of the downstream IgH chromatin for potential switch recombination. PMID- 1760403 TI - Organization and expression of the lambda-like genes that contribute to the mu psi light chain complex in human pre-B cells. AB - Lambda-like genes encode a polypeptide chain that associates with VpreB and mu chain in the so-called mu-psi light chain complex specifically expressed in pre-B cells. In humans, the lambda-like gene cluster contains three genes, termed 14.1, 16.1, and F lambda 1. The 14.1 gene contains three exons and was previously sequenced. The 16.1 and F lambda 1 have been isolated from cosmid libraries. They both contain only the exons 2 and 3 that appear highly homologous to their 14.1 counterparts. The lambda-like gene cluster has been mapped on chromosome 22, close and distal to the BCR gene, in the order (14.1; F lambda 1) and 16.1. Hybridization with the 14.1 exon 1 probe did not detect an equivalent on 16.1 and F lambda 1 genes, but instead, only revealed the X6 gene, that was previously identified 5 kb upstream of the IGLC locus. It appears, therefore, that the gene organization of the lambda and lambda-like loci is strikingly similar, with a three-exon-containing gene 5' of a series of J lambda-C lambda or J lambda-C lambda-like tandemly organized genes. Analysis of the transcripts in a 8 week old human fetal liver clearly indicated that 14.1 was the only functional gene of the lambda-like cluster. Various forms of transcripts resulting from alternate splicing have been characterized. The major component consisted of a full-length (exons 1-2-3) mRNA, whereas a minor (1-3) transcript was identified. Only the full-length transcript could encode a functional polypeptide chain corresponding to the 22 kDa light chain surrogate. PMID- 1760404 TI - Regulation of anti-immunoglobulin-induced B lymphoma growth arrest by transforming growth factor beta 1 and dexamethasone. AB - Exposure of the murine B lymphoma cell line WEHI-231 to anti-immunoglobulin M (anti-IgM) antibodies results in growth arrest in the G1 phase of the cell cycle followed by programmed cell death. This response may be analogous to the clonal deletion of immature B cells that occurs when the membrane IgM on these cells is engaged by self-antigens or by anti-IgM antibodies. Thus the WEHI-231 cell line has been a useful in vitro system for identifying factors that modulate anti-Ig induced growth inhibition and/or clonal deletion. For example, both antigen induced tolerance induction in immature B cells and anti-Ig-induced growth arrest of WEHI-231 cells are prevented by bacterial lipopolysaccharide or by the products of activated T helper cells. Since negative signaling by membrane Ig may also be regulated by additional factors, we asked whether other cytokines or hormones would regulate the growth of WEHI-231 cells or its response to anti-IgM antibodies. We show here that two compounds that are generally immunosuppressive, transforming growth factor beta 1 (TGF-beta 1) and the synthetic corticosteroid, dexamethasone, blocked the ability of lipopolysaccharide and T cell-derived lymphokines to protect WEHI-231 cells from anti-IgM-induced growth arrest. In addition, TGF-beta 1 and dexamethasone slightly inhibited the growth of WEHI-231 cells by themselves and also potentiated the growth inhibitory effects of anti IgM antibodies. Thus for WEHI-231 cells, TGF-beta 1 and dexamethasone are inhibitory factors which favor growth arrest. PMID- 1760405 TI - TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes. AB - Immunoglobulin (Ig) class switching appears to be preceded by induction of germ line transcripts. In this report, we demonstrate that transforming growth factor beta (TGF-beta) induces germ-line transcripts of both the IgA subclasses (IgA1 and IgA2) in Branhamella catarrhalis (BC)-activated human spleen B cells. Two germ-line bands, one of approximately 1.85 kb and the other of approximately 1.6 kb, could be seen in cultures treated with TGF-beta. The approximately 1.85 kb band contains mRNA for a germ-line transcript of the membrane form. This band co migrates with the productive secreted form of alpha mRNA. The other, shorter form of approximately 1.6 kb did not correlate in size with any known form of productive alpha mRNA and contained the secreted form of germ-line alpha mRNA. The induction of alpha germ-line transcripts was accompanied by a concomitant suppression of mu and gamma mRNA. We have also identified the location of a putative I alpha sequence (designated according to the generally accepted nomenclature) within approximately 0.5 kb upstream to the switch alpha (S alpha) region. The relative proportions of IgA-subclass-specific mRNA in TGF-beta stimulated spleen B cells are concordant with the distribution pattern seen in pokeweed mitogen (PWM)-stimulated spleen mononuclear cells (MNC), which was 89 and 11% for the IgA1 and the IgA2 mRNA respectively. These results suggest a role of TGF-beta in regulating IgA class switching in human B lymphocytes. PMID- 1760406 TI - Structure of TGF-beta 1-induced human immunoglobulin C alpha 1 and C alpha 2 germ line transcripts. AB - We have characterized the structure of the human immunoglobulin C alpha 1 and C alpha 2 germ-line transcripts that are synthesized upon treatment of human B lymphocytes with Branhamella catarrhalis (a B cell mitogen) and transforming growth factor beta 1 (TGF-beta 1). These transcripts initiate upstream of the switch alpha 1 and switch alpha 2 regions and contain, together with the C alpha 1 and C alpha 2 sequences, additional exons designated according to the generally accepted nomenclature I alpha 1 and I alpha 2 respectively. The I alpha exons are spliced directly onto the acceptor splice site of the CH1 domains of the C alpha 1 and C alpha 2 genes. As in other previously characterized germ-line transcripts, stop codons present in all three reading frames prevent translation of the C alpha 1 and C alpha 2 heavy-chain coding sequences. The longest open reading frame (ORF) present in the I exons can code for a polypeptide of only 26 amino acids. The human I alpha exons do not show any significant sequence homology with the corresponding mouse I alpha exon. However, comparison of nucleotide sequences of the genomic mouse and human I alpha regions demonstrated the presence of an approximately 300 bp highly conserved element located immediately upstream of the transcription initiation sites of the human and mouse C alpha germ-line transcripts. The isolation of the C alpha 1 and C alpha 2 germ line transcripts will further facilitate the characterization of the molecular events responsible for the regulation of the human C alpha heavy chain loci. PMID- 1760407 TI - The immunoglobulin light chain related protein lambda 5 is expressed on the surface of mouse pre-B cell lines and can function as a signal transducing molecule. AB - Abelson Leukemia Virus-transformed mouse cell lines with an early pre-B phenotype carry partially rearranged or unrearranged Ig-H genes and consequently do not express intact IgM-H protein (mu protein). Such early mu- pre-B cells express an intracellular protein complex of the pre-B cell specific 22 kDa protein lambda 5 and a 16 kDa protein designated p16. Late pre-B cell lines which carry a rearranged IgM-H chain gene in which a continuous translational reading frame has been established in the fused V-D-J element express intact mu-protein, which forms an intracellular complex with lambda 5 and p16. We show here that both the lambda 5/p16 or the mu/lambda 5/p16 complexes can be immunoprecipitated from lysates of cells surface labeled with 125I. Thus early pre-B cells express the lambda 5/p16 complex on the cell surface in the absence of mu protein, while mu+ late pre-B cells express a surface mu/lambda 5/p16 complex. To investigate a possible signal transduction function of the lambda 5/p16 and mu/lambda 5/p16 complexes on the surface of pre-B cell lines we measured the changes in intracellular free Ca2+ after treatment of cells with anti-lambda 5 or anti-mu antibodies. Two mu- early pre-B cell lines showed a rapid and transient increase in intracellular free Ca2+ when incubated with anti-lambda 5 antibodies but not when incubated with anti-mu, while the mu+ late pre-B cell line CB32 showed a rapid and transient increase in intracellular Ca2+ after incubation with anti lambda 5 or anti-mu. These results show that both the lambda 5/p16 and the mu/lambda 5/p16 cell surface protein complexes can transduce an external signal to the inside of the cell, which implicates these complexes in the regulation of pre-B cell physiology. PMID- 1760408 TI - Comparison of protein tyrosine phosphorylation and morphological changes induced by IL-2 and IL-3. AB - We constructed cell lines which can proliferate in response to IL-2 or IL-3 by introducing a wild-type and mutant forms of cDNAs encoding the human IL-2R p75 chain into an IL-3 dependent hematopoietic cell line which expresses the p55 chain of the IL-2R. We compared early events that were induced in these cells by IL-2 and IL-3. Analysis of protein tyrosine phosphorylation showed that two common protein bands, pp95 and pp90, were phosphorylated by stimulation of either IL-2 or IL-3, suggesting the possible sharing of part of a signal transduction pathway between IL-2R and IL-3R. Comparison of protein tyrosine phosphorylation profiles induced by IL-2 and IL-3 among a variety of cell lines revealed that the pp90 band is the common tyrosine phosphorylation substrate in the cell lines examined, although the general tyrosine phosphorylation pattern differed in each cell line. Mutant p75 molecules incapable of inducing tyrosine phosphorylation could bind and internalize IL-2, but could not support cell growth. We also found that swift changes of cytoskeletal protein organization are one of the early events caused by signal transduction through either IL-2R and IL-3R. Reorganization of cytoskeletal proteins seems to be associated with protein phosphorylation, as a significant portion of pp90 was found in a detergent soluble fraction in IL-2 or IL-3 treated cells. PMID- 1760409 TI - Antigen-specific directional target cell lysis by perforin-negative T lymphocyte clones. AB - Despite a number of reports indicating that perforin, a pore-forming protein, is the primary effector molecule mediating specific target cell lysis by cytotoxic T lymphocytes (CTL), several lines of evidence suggest the existence of perforin independent mechanisms. We established class II-restricted, soluble protein specific CD4+ T cell clones with killing function which do not express a detectable amount of perforin and perforin mRNA. Nevertheless, these clones induced cytolysis and DNA fragmentation of target cells in a specific and highly directional manner which was not inhibitable by antibody against TNF/lymphotoxin. These data not only indicate the existence of cytotoxic T cell subsets which do not utilize perforin, but also suggest that perforin is not mandatory for specific target lysis by T cells. PMID- 1760410 TI - Cell adhesion by membrane-bound paf-acether. AB - It was recently shown that paf-acether (paf) synthesized in different cell types remains partly cell-associated. In the present work, we tested the hypothesis that cell-associated paf might in fact remain exposed on the external plasma membrane and be able to exert its biological functions. Human polymorphonuclear neutrophils (PMN), stimulated with either opsonized zymosan or ionophore A23187 and then thoroughly washed, induced aggregation of human and rabbit platelets in a time- and dose-dependent manner, whereas no aggregation was observed in the presence of unstimulated cells. Aggregation was inhibited by the specific paf antagonists BN 52021 or WEB 2086. Treatment of stimulated PMN with specific anti paf antibody before addition to platelets abolished the PMN--paf-mediated aggregation. Microscopic observation of human platelets revealed that aggregates formed by platelets were attached to the neutrophil surface. Paf remained associated with PMN following human PMN-human platelet interaction, in contrast to human PMN-rabbit platelet incubation, where it disappeared from both PMN and platelet surfaces. Our results strongly support the hypothesis that a fraction of cell-associated paf synthesized in neutrophils is located on and/or in the external plasma membrane, where it can act upon other cells by direct cellular contact. Such a mechanism of cell adhesion might play a role in cell physiology (neutrophils but also monocytes/macrophages, eosinophils, and lymphocytes), as well as in the onset and perpetuation of immune and inflammatory reactions. PMID- 1760411 TI - Rat thymic epithelial cells in culture constitutively secrete IL-1 and IL-6. AB - To study the in vitro interactions between rat thymic non-lymphoid cells and thymocytes, we established a system for long-term cultivation of thymic epithelial cells (TEC). TEC were cultivated and successfully propagated for over 8 months in RPMI 1640 medium containing 15% FCS, dexamethasone, insulin, epidermal growth factor, and poly-L-lysin as an adhesive matrix. Their epithelial nature has been confirmed using monoclonal anti-cytokeratin (CK) antibodies. More than 95% of these cells were reactive with K 8.13 and CK 8 mAbs, which are pan epithelial markers for rat TEC in situ. An epithelial cell clone (TE-R 2.5) established from a long-term TEC culture was 100% reactive with these anti-CK antibodies. Phenotypic analysis of TEC cultures was performed by a large panel of mAbs reactive with a subset of rat TEC or CK polypeptides as well as UIex europaeus agglutinin I using a streptavidin-biotin immunofluorescence assay. Although the results obtained demonstrated phenotypic heterogeneity among these cells, most cultures, including the TE-R 2.5 clone, were of subcapsular/medullary phenotype. Medium conditioned by TEC cultures exhibited IL-1 and IL-6 activities when tested on D10S and B9 sensitive cell lines, respectively. Cytokine activities were neutralized (IL-1) or significantly inhibited (IL-6) by specific polyclonal antibodies. In addition, both anti-IL-1 and anti-IL-6 antibodies reacted with TEC in culture and epithelial (CK-positive) cells on thymic cryostat sections, indicating that thymic epithelium provides an important intrathymic source for molecules contributing to T cell activation. PMID- 1760412 TI - Perforin and granzyme B as markers for acute rejection in heart transplantation. AB - Histological analysis of endomyocardial biopsies (EMB) is regarded as the most satisfactory technique for monitoring crisis of rejection in heart transplanted patients. In this study, 42 biopsies from 14 patients who underwent heart transplantation were examined. Three patients did not present any rejection crisis at the date of the biopsy analysis, six were examined during an early rejection crisis (day 7-70 post-graft), and five were examined during a late rejection crisis (day 74-960 post-graft). Since granzyme B and perforin are proteins associated with cell lysis histological grading and cell phenotype analysis, in situ hybridization using granzyme B and perforin [35S]RNA probes was performed on 30 EMB to characterize the cytolytic activation of heart infiltrating cells. Our data suggest that granzyme B and perforin could be used as predictive markers for acute rejection in patients with early rejection crisis. Their detection might be an indication to administrate corticoids to resolve an acute rejection crisis. In contrast, their absence in patients with late rejection crisis appears as a good prognostic factor for the outcome of rejection and raises the question of the necessity to treat such patients with additional corticoid treatment. PMID- 1760414 TI - Audit in obstetrics. PMID- 1760413 TI - Infection of human CD4+ rabbit cells with HIV-1: the possibility of the rabbit as a model for HIV-1 infection. AB - Although human T cell surface glycoprotein CD4 is the cellular receptor for human immunodeficiency virus 1 (HIV-1), the introduction of the human CD4 gene into murine cells does not render them susceptible to HIV-1 infection. Here we have established rabbit transfectant cell lines expressing human CD4 on the cell surface and demonstrated that the CD4+ rabbit transfectants could be readily infected by HIV-1 by co-cultivating with a HIV-1-infected human MOLT-4 T cell line (MOLT-4/HIV). Avid syncytia formation was observed upon co-cultivation and the syncytia abundantly produced HIV-1 mature particles, as revealed by electron microscopy. A significant increase of HIV-1 p24 antigen was also detected in the culture supernatant. The syncytia formation was blocked by pretreating the transfectant with anti-human CD4 or by pretreating the MOLT-4/HIV with anti-HIV-1 serum obtained from an infected individual, indicating that the syncytia formed as a result of the interaction of human CD4 on the rabbit transfectant with the HIV-1 envelope protein expressed on MOLT-4/HIV. In contrast, only a very small proportion of the rabbit transfectants expressed HIV-1-specific antigens upon infection with an HIV-1 stock. This may indicate that, although rabbit cells have partially acquired susceptibility to HIV-1 by transfection of human CD4 gene, rabbit cells may further require such a molecule as might be provided by MOLT-4 to become fully susceptible to HIV-1 infection. The possibility of the rabbit as a model for HIV-1 infection is also discussed. PMID- 1760415 TI - The flying squad. PMID- 1760416 TI - Criteria for standards of management of women with an abnormal smear. PMID- 1760417 TI - Evaluating the quality of the maternity services--a discussion paper. AB - OBJECTIVE: A review of the use of computer collected audit data in assessing the quality of maternity services. SETTING: All maternity units managed by the North West Thames Regional Health Authority. RECOMMENDATIONS: A system of audit must supply information that is both credible and of interest to clinicians managers and consumers. The information should be adjusted for differences in populations to allow valid comparisons between units. It needs to be presented in an easily digested form. One way of implementing audit would be to establish a regional group representative of clinicians, patients and managers who would initially interpret the data and make recommendations. A local group of similar composition would be asked to comment on and respond to these with a plan for the following year. Changes would be monitored by analysis of the routinely collected data. CONCLUSIONS: Medical audit in the maternity services requires new concepts if it is to influence the quality of clinical care and the use of resources available to provide that care. The appropriate balance needs to be found between the perspectives of clinicians, patients and managers. A major challenge is the collection of valid data. This has largely been overcome by the St Mary's maternity information system. The next stage is to devise a system of audit that is epidemiologically sound and is acceptable to those who will be asked to implement the lessons that emerge. Only then will it be possible to determine whether clinical practice and the use of resources can be altered to the benefit of patients. PMID- 1760418 TI - Is genetic susceptibility to pre-eclampsia conferred by homozygosity for the same single recessive gene in mother and fetus? AB - OBJECTIVE: To determine whether any simple, purely genetic mechanism can account for susceptibility to pre-eclampsia. DESIGN: Six simple Mendelian models of inheritance were considered, and predictions concerning the incidence of pre eclampsia in various family members of index cases were calculated for each genetic model. Data were then extracted from published family studies in which a suitable disease definition had been used, and compared to our theoretical expectations. RESULTS: Only one of the genetic models considered, in which both mother and fetus must express the same recessive gene to confer susceptibility, was consistent with the observed incidence values for relatives of index cases. This model was also consistent with the putative association with HLA-DR4, but could not account for the comparative rarity of pre-eclampsia in parous women. CONCLUSION: Homozygosity for a single recessive gene shared by mother and fetus, unlike five other genetic mechanisms tested, is consistent with published family studies in pre-eclampsia, and should be considered the best working hypothesis at present. PMID- 1760419 TI - The obstetric and neonatal outcome of pregnancy in women with a previous history of infertility: a prospective study. AB - OBJECTIVE: To compare the frequency of common antenatal problems, the amount of antenatal surveillance and the obstetric and neonatal outcome in women with and without a history of infertility. DESIGN: A prospective cohort study with age and parity matched controls. SETTING: A single consultant unit at the Jessop Hospital for Women, Sheffield, over a 22-month period. SUBJECTS: 114 women with a history of infertility who reached 16 weeks gestation with a singleton live fetus and 114 control women matched for age and parity. MAIN OUTCOME MEASURES: Frequency of antepartum complications, amount of antepartum surveillance, obstetric and neonatal outcome. RESULTS: Common antenatal complications were not increased. In the infertility compared with the control group, the relative risk of requiring an emergency caesarean section was 2.43 (95% CI 1.05-5.63). There was no difference in birthweight. CONCLUSION: Many of the previously observed differences in outcome of pregnancy in women after infertility compared with those without are associated with age and parity but these characteristics do not explain the increased frequency of emergency caesarean section. PMID- 1760420 TI - The prevalence, aetiology and clinical significance of pseudo-sinusoidal fetal heart rate patterns in labour. AB - OBJECTIVE: To investigate the prevalence of sinusoidal and pseudo-sinusoidal fetal heart rate (FHR) patterns in labour and the relation between the characteristics of the FHR pattern and fetal outcome. DESIGN: A prospective observational study over a 6-month period in which all women who had continuous FHR monitoring in labour had their intrapartum cardiotocographs (CTGs) scrutinized for the presence of sinusoidal or pseudo-sinusoidal FHR patterns. SETTING: John Radcliffe Hospital, Oxford. SUBJECTS: 1520 women who had fetal monitoring during labour for various reasons. MAIN OUTCOME MEASURES: Both internal (electrocardiographic) and external (ultrasound) recordings of the FHR were analysed. Abnormal FHR patterns were related to obstetric characteristics and fetal outcome in terms of Apgar scores, umbilical artery pH and admission to the special care unit. RESULTS: No true sinusoidal FHR patterns were observed, but pseudo-sinusoidal FHR patterns were found in 230 of the 1520 CTGs examined (15%). Of these, 219 were classified as minor (amplitude 5-15 beats/min) and 11 as intermediate (amplitude 16-24 beats/min). Major pseudo-sinusoidal FHR patterns (amplitude greater than 24 beats/min) were not observed. Minor pseudo-sinusoidal FHR patterns had a mean duration of 21 (SD 13) min and typically occurred once or twice early in labour. Using logistic regression analysis a significant, independent relation was demonstrated between the presence of minor pseudo sinusoidal FHR patterns and the use of pethidine (RR 1.84, 95% CI 1.3 to 2.59, P less than 0.0001) and epidural analgesia (RR 1.85, 95% CI 1.24 to 2.76, P less than 0.001). Intermediate pseudo-sinusoidal FHR patterns were found in association with both in utero fetal sucking and transient episodes of fetal hypoxia such as that caused by periodic umbilical cord compression. CONCLUSION: Pseudo-sinusoidal FHR patterns in labour will usually be associated with a normal fetal outcome but a careful fetal assessment is mandatory. PMID- 1760421 TI - The management of prolonged pregnancy--an analysis of women's attitudes before and after term. AB - OBJECTIVE: To determine the attitude of pregnant women to a proposal of conservative management of prolonged pregnancy. DESIGN: A prospective questionnaire-based survey. SETTING-Louise Margaret Maternity Wing, Cambridge Military Hospital, Aldershot. SUBJECTS: 500 pregnant women initially at 37 weeks gestation considered suitable for the potential conservative management of prolonged pregnancy. RESULTS: Despite a stated obstetric preference for conservative management, only 45% of the women at 37 weeks gestation were agreeable to conservative management; of those undelivered by 41 weeks gestation 31% still desired conservative management. This significant decrease was unaffected by parity or certainty of gestational age. CONCLUSIONS: Most pregnant women are unwilling to accept the conservative management of prolonged pregnancy and become more reluctant to do so if undelivered by 41 weeks gestation. Women are not as favourably disposed towards the conservative management of pregnancy as has been suggested previously. PMID- 1760422 TI - Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility. AB - OBJECTIVE: To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility. DESIGN: Women randomly allocated to one of three treatment protocols. SETTING: Northern Regional Fertility Centre. SUBJECTS: 59 couples with unexplained infertility of more than 3 years duration. INTERVENTIONS: Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle. MAIN OUTCOME MEASURES: Pregnancy resulting in a live birth. RESULTS: Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT. CONCLUSIONS: This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT. PMID- 1760423 TI - United Kingdom colposcopy survey, British Society for Colposcopy and Cervical Pathology. AB - OBJECTIVE: To audit various aspects of colposcopy practice throughout the United Kingdom on behalf of BSCCP. DESIGN: A postal questionnaire was circulated to those responsible for colposcopy services in all districts in the United Kingdom in 1988, followed by a smaller survey of 40 clinics in 1990 to detect any trends. MAIN OUTCOME MEASURES: Information was sought on colposcopy workload, referral criteria, treatment method and follow-up, waiting times, staffing and training. RESULTS: There was a 71% response to the national survey of 1988 practice which alone accounted for 80,000 new referrals for colposcopy. Cytological criteria for colposcopy referral were generally liberal. In 1988 laser ablation was the single most popular method, and waiting times for colposcopy varied, with 79% of patients being seen within 8 weeks of referral. Colposcopy clinics run by non gynaecologists, mainly genito-urinary physicians, were reported by 32% of districts. Half the respondents did not have accurate statistics, only 17% being computerized, and dissatisfaction with clerical support was widespread. Resources are required to improve administration and data collection. The principal findings from the 1990 data subset were a 10% reduction for new patient referrals compared with 1988 and the use of diathermy loop excision by one-third as their preferred treatment. CONCLUSIONS: This audit of colposcopy has provided useful information as well as a means of monitoring trends in colposcopy activity in the future. PMID- 1760424 TI - A multicentre study of coagulation and haemostatic variables during oral contraception: variations with four formulations. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland. AB - OBJECTIVE: To explore the extent to which progestogen type and oestrogen and progestogen dose may modify the effects of combined oral contraceptives (OC) on coagulation and haemostasis. DESIGN: Randomized double-blind clinical trial. SETTING: Gynaecological clinics in Salvador (Brazil), Santiago (Chile), Singapore, and Dublin (Ireland). SUBJECTS: 622 women aged 18-35 years who had opted for oral contraception. A contrast group of 155 women who were not to receive OC was also studied. Both groups included approximately equal numbers from each of the four centres. INTERVENTIONS: Treatment of approximately equal numbers of women at each centre with one of the following OC preparations for at least 12 months: Norethisterone acetate (NEA) 1 mg + ethinyl oestradiol (EE) 50 micrograms; levonorgestrel (LNG) 250 micrograms + EE 50 micrograms; LNG 250 micrograms + EE 30 micrograms; LNG 150 micrograms + EE 30 micrograms. MAIN OUTCOME MEASURES: Changes over 12 months in 12 coagulation and haemostatic variables. RESULTS: At 12-month follow-up, the women on each OC preparation showed acceleration of prothrombin time and increase in factor X and fibrinogen. With the OC containing NEA there was also a persistent rise in factor VIIC, and reduction of antithrombin III and alpha 2-antiplasmin. The formulation which contained low doses of both LNG and EE showed the least adverse coagulation changes. Large increases in fibrinolysis were found in all OC groups. CONCLUSIONS: The adverse effects of combined OC on clotting are affected by the type and dose of progestogen as well as the dose of oestrogen. PMID- 1760425 TI - Self-reported long-term outcomes of hysterectomy. AB - OBJECTIVES: To investigate women's perceptions of and satisfaction with the long term outcomes from a hysterectomy performed between 2 and 10 years ago and to determine whether satisfaction is related to demographic factors, factors associated with the hysterectomy, and the number or type of perceived benefits and problems associated with the hysterectomy. DESIGN: Retrospective survey by telephone interview and postal questionnaire of 236 women who had a hysterectomy between 2 and 10 years ago. SETTING: Women who had had a hysterectomy were identified from a community survey in the Hunter Region of NSW, Australia. SUBJECTS: Two hundred and thirty-six women who self-reported having had a hysterectomy between 2 and 10 years ago. MAIN OUTCOME MEASURES: Perceived benefits resulting from the hysterectomy; perceived physical and psychological problems caused by the hysterectomy; satisfaction with care. RESULTS: Relief from heavy bleeding was the most frequent benefit (57%) and the most important benefit (32%). Most of the women reported improvements in symptoms experienced before hysterectomy but more than half the women had symptoms which they believed had been worsened or caused by the hysterectomy. Despite this, high levels of satisfaction with the operation were reported. CONCLUSION: The results highlight the need to examine more closely decision-making about treatment for menstrual symptoms such as heavy bleeding. PMID- 1760426 TI - Ureteric obstruction in pregnancy--diagnosis and management. AB - OBJECTIVE: To discuss the aetiology, diagnosis and management of ureteric obstruction in pregnancy and to describe the use of double-pigtail ureteric stents in a series of 10 patients. DESIGN: Retrospective study of women presenting to a maternity unit in whom the diagnosis of ureteric obstruction is reached. SETTING: Southmead Hospital in Bristol; a large district general hospital with a throughput of around 6000 maternity patients per year. SUBJECTS: 10 women (8 in their first pregnancy, 1 in her second and 1 in her third; mean age 29.2 years (range 18-31 years). INTERVENTIONS: Double-pigtail ureteric stents were electively passed after a diagnosis of ureteric obstruction. Stents remained in situ for a mean 15.5 weeks (range 8-25 weeks) and were electively removed 4-6 weeks post partum. RESULTS: Nine women progressed uneventfully through the remainder of their pregnancy. One developed strangury, haematuria and discomfort after stent insertion. Seven women had normal vaginal deliveries, two assisted vaginal deliveries and one was delivered by caesarean section. None required to have external urinary drainage. CONCLUSIONS: Double-pigtail ureteric stents are easy to place and remove and are well tolerated. They provide a simple, safe and effective method of internal upper urinary tract drainage in ureteric obstruction in pregnancy. PMID- 1760427 TI - The Stamey endoscopic bladder neck suspension: a clinical and urodynamic investigation, including actuarial follow-up over four years. AB - OBJECTIVE: To assess a modified Stamey endoscopic bladder neck suspension as a management for genuine stress incontinence in women unsuitable for colposuspension because of vaginal narrowing or inefficient voiding. DESIGN: Uncontrolled observational study. SETTING: Regional university gynaecological urology unit. SUBJECTS: A hundred women, median age 58 years, with genuine stress incontinence confirmed by urodynamic investigation; 65 had had previous surgery for the same problem. TREATMENT: A Stamey procedure with monofilament nylon and short buffers of silastic tubing at each anchor site. MAIN OUTCOME MEASURES: Urodynamic reassessment 3 months after surgery and clinical follow-up for up to 4 years, using life table methods. The median follow-up was 27 months. RESULTS: At 3 months the objective cure rate was 83%. Subjectively the cure rates at 4 years were 53% in patients under 65 years of age and 76% in those who were older. Overall mean bladder capacity decreased from 506 to 458 ml after surgery (P less than 0.05) and, in those who were cured, mean peak flow rate fell from 25.5 to 19.6 ml/s (P less than 0.05). The urethral functional length and the pressure transmission in the proximal three quarters were increased by successful surgery (P less than 0.01) but the resting urethral profile, voiding pressure and the frequency of detrusor instability were unchanged. CONCLUSIONS: This modification of the Stamey operation has an important role in the management of elderly patients those with previous unsuccessful operations, and those with inefficient voiding pre-operatively. PMID- 1760428 TI - The surgical management of vaginal vault prolapse. AB - OBJECTIVE: A review of the results of surgery for vaginal vault prolapse following hysterectomy. DESIGN: A retrospective review of all patients treated surgically for vaginal vault prolapse between 1981 and 1990 in one hospital. SETTING: St George's Hospital, London. SUBJECTS: 28 women. INTERVENTIONS: The 28 patients underwent 33 operations, either a colposacropexy (23 procedures) or a Zacharin procedure (10 procedures). Of the 28 women 25 were seen in the gynaecological clinic within the last year. MAIN OUTCOME MEASURES: Pre- and post operative data and any interim prolapse surgery was recorded. Success of the procedure in terms of cure, urinary complications, infection and sexual function. RESULTS: The mean follow-up time was 17.1 months for the colposacropexy and 33 months for the Zacharin. The cure rate for colposacropexy was 91% and that for the Zacharin procedure was 70%. The two commonest complications were development of a voiding difficulty and infection. Three women developed voiding difficulty following the Zacharin and one following colposacropexy. Two women following colposacropexy required removal of the Mersilene mesh due to a persistent discharging sinus. CONCLUSION: The colposacropexy had a better success rate and, as it is a simpler operation to perform, has become the operation of choice in this unit. It is, however, associated with a risk of infection which can necessitate removal of the supporting mesh. PMID- 1760429 TI - Relations between the fetal circulation and pituitary-thyroid function. AB - OBJECTIVE: To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN: A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS: 38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS: Cordocentesis. MAIN OUTCOME MEASURES: Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS: Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION: In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment. PMID- 1760430 TI - Patient acceptability of laser and cold coagulation therapy for pre-malignant disease of the uterine cervix. AB - OBJECTIVE: To determine patient acceptability of cold coagulation and laser treatment for cervical intraepithelial neoplasia (CIN). DESIGN: A prospective study with alternate allocation. SETTING: Teaching hospital in London. SUBJECTS: 155 women requiring treatment for CIN. MAIN OUTCOME MEASURES: Time taken to complete the treatment; visual analogue scores for pain experienced, anxiety felt and acceptability of the procedure; post treatment bleeding and discharge, and follow-up smear. RESULTS: Cold coagulation treatment was found to be quicker and less painful than laser treatment, there were no other significant differences between the two methods of treatment. CONCLUSION: Cold coagulation is a more acceptable form of treatment for CIN than laser. PMID- 1760431 TI - Changes in flow velocity waveforms in umbilical and uterine artery following haemodialysis. Case report. PMID- 1760432 TI - Epidural analgesia--a cause of transient impairment of the utero-placental circulation? PMID- 1760433 TI - The flying squad--an expensive and potentially dangerous practice in modern obstetrics. PMID- 1760434 TI - Absence of diurnal variation in urinary chorionic gonadotrophin excretion at 8-13 weeks gestation. PMID- 1760435 TI - The effects of pregnancy on previous incontinence surgery. Case report. PMID- 1760436 TI - Colpo-needle suspension for the treatment of urinary stress incontinence--a new surgical technique. PMID- 1760437 TI - Litigation in obstetrics and gynaecology. Commentary. PMID- 1760438 TI - Litigation in obstetrics and gynaecology. Commentary. PMID- 1760439 TI - Maternal and fetal haemodynamics in hypertensive pregnancies during maternal treatment with intravenous hydralazine or labetalol. PMID- 1760440 TI - Contents of essential and toxic mineral elements in Swedish market-basket diets in 1987. AB - Market baskets containing sixty food items included in the average Swedish diet were purchased from three shops in four major Swedish cities during autumn 1987. Food items were selected on the basis of food-balance-sheet data. Freeze-dried homogenates representative of each city were analysed for twelve essential or toxic mineral elements. The energy content of the market baskets (11.5 MJ) corresponded to the reference value for male adults. At this energy level the contents of calcium (1180 mg), magnesium (300 mg), iron (16 mg), zinc (12 mg) and selenium (44 micrograms) were above or close to the Swedish recommended daily intakes. The contents of manganese (3.7 mg) and molybdenum (150 micrograms) were within and that of copper (1.2 mg) was below the safe and adequate intake values given in the US recommended dietary allowance (Food and Nutrition Board, National Research Council, 1989). The content of nickel was 82 micrograms. The contents of lead (17 micrograms), cadmium (12 micrograms) and mercury (1.8 micrograms) in the daily diet were low compared with the provisional tolerable intakes set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (World Health Organization, 1972, 1989). The market basket contents of Ca, Mg, Fe and Zn calculated from values in the Swedish food composition tables were close to the analysed values, indicating that the Swedish food tables provide relevant information for the estimation of the dietary supply of these elements. PMID- 1760441 TI - The effect of energy source and feeding level on the hormones of the entero insular axis and plasma glucose in the growing pig. AB - The aim of the experiment was to test the theory that accustoming pigs to a high fat diet causes exaggerated gastric inhibitory polypeptide (GIP) secretion in response to a high-fat meal, and to determine whether hypersecretion of GIP could be related to an increase in the GIP content of the small intestine. Twenty-four pigs were fed one of three dietary regimens for 11 weeks: a high-carbohydrate diet (CL), or a high-fat diet (FL), both fed at 1.46 MJ gross energy (GE)/kg live weight0.75 per d, or a high-fat diet (FH) fed at 2.10 MJ GE/kg live weight0.75 per d. At the end of the period two acute tests were performed. For acute test 1 the accustomed meal (diets CL, FL and FH) and for acute test 2 a standard high fat meal (diet FL) were given; blood samples were taken during the next 5 h and analysed for GIP, insulin and glucose. Integrated increases in hormone and glucose levels were compared by analysis of variance (0-300 min). In acute test 1 there were significantly different plasma GIP concentrations between groups (CL greater than FH greater than FL; P less than 0.05). Plasma insulin concentrations were significantly higher in group CL compared with groups FL and FH (P less than 0.002). There were no differences in glucose levels. In acute test 2 integrated increases in plasma GIP (0-300 min) concentrations were not significantly different; however, GIP (0-45 min) concentrations were significantly higher in group FH than in groups CL and FL (P less than 0.05). There were no differences in plasma insulin concentrations. Plasma glucose (0-300 min) concentrations were significantly higher in groups FL and FH compared with group CL (P less than 0.05). The GIP content of tissue samples taken at the end of the experiment from the duodenum, jejunum, upper and lower ileum decreased significantly in a proximal to distal direction (P less than 0.001). Diet FH significantly increased the average GIP content of the small intestine compared with diets CL and FL (P less than 0.05). It is concluded that fat meal-stimulated GIP secretion was enhanced by increased feeding level during a pre-treatment phase, possibly due to an increase in GIP synthesis in the small intestine. The high-fat diet caused glucose intolerance after a high-fat meal. This may be due in part to the action of dietary fat on glucose transport and metabolism. PMID- 1760442 TI - Urease (EC 3.5.1.5) inhibition in the sheep rumen and its effect on urea and nitrogen metabolism. AB - The urease (EC 3.5.1.5) inhibitor, phenylphosphoryldiamidate (PPDA), was given by continuous infusion into the rumen of two sheep nourished by intragastric infusion and into either the rumen or abomasum of four sheep given a pelleted diet containing 119 g crude protein (nitrogen x 6.25)/kg dry matter. PPDA was given at 1 g/d in infusion sheep and 1.5 g/d in the normally-fed sheep. Measurements of urea kinetics were made using single injections of [14C]urea. Urease inhibition was complete within 24 h of starting PPDA infusions to the rumen; in this time-period, urea concentration in rumen contents reached equilibrium with that in plasma and this situation persisted until infusions were terminated. Relative to the control periods, plasma urea and rumen ammonia concentrations were unchanged but urea irreversible loss rate decreased by 26% in infusion sheep and 33% in fed sheep when PPDA was given. Urinary urea excretion was not affected, hence urea degradation, measured by difference, decreased by 77 and 58% respectively in response to urease inhibition. Administration of PPDA to the abomasum resulted in a reduction in rumen urease activity to about 40% of control values but had no effect on urea metabolism. Differences between treatments in daily nitrogen retention were not significant, indicating that under the dietary conditions imposed in these experiments, even substantial changes in urea recycling had only minor effects on the overall N economy of the animal. PMID- 1760443 TI - The effect of dietary taurine content on the plasma taurine concentration of the cat. AB - The essential role of taurine in the diet of the cat has been well documented and a deficiency of this nutrient is known to be responsible for a number of clinical conditions. At present, the National Research Council (1986) recommendation for the minimum dietary requirement of the kitten is 400 mg/kg dry matter and for a pregnant cat is 500 mg/kg dry matter. However, these minima were established by feeding the animals on semi-purified diets and, therefore, may be inappropriate for other dietary regimens. The aim of the present study was to investigate the effect of feeding a series of specially prepared diets containing different concentrations of taurine (canned diets 1475-5750 mg/kg dry matter, dry diets 811 1240 mg/kg dry matter) on the plasma taurine concentration of the cat. All diets were fed solus for 6 weeks and plasma taurine concentration was measured every 2 weeks. The results showed that to maintain plasma taurine values in the 'normal' range (less than 60 mumol/l), a canned diet must supply at least 39 mg taurine/kg body-weight per d and a dry diet at least 19 mg/kg body-weight per d; a cat fed on a semi-purified diet need only achieve a daily intake of at least 10 mg taurine/kg body-weight to maintain an adequate circulating level of taurine. The cause of the reduced availability of taurine from these diets is not yet known. Furthermore, repletion of plasma concentration above 60 mumol/l can be achieved within 2 weeks of feeding an adequate diet. PMID- 1760444 TI - Nitrogen transactions along the digestive tract of lambs concurrently infected with Trichostrongylus colubriformis and Ostertagia circumcincta. AB - Twelve lambs, paired on the basis of live weight, were cannulated in the abomasum, in the proximal jejunum approximately 4 m distal to the pylorus and in the terminal ileum. Six were infected with 3000 Trichostrongylus colubriformis and 3000 Ostertagia circumcincta larvae each day for 18 weeks and the remainder were pair-fed to individual infected lambs. All animals were offered ryegrass (Lolium perenne)-white clover (Trifolium repens) pasture, cut daily. Dry matter (DM) intake, live weight, faecal egg concentration, plasma pepsinogen and plasma protein concentrations were measured weekly. During weeks 7 and 17 after commencement of infection, the flow of digesta along the gastrointestinal tract was measured together with enteric plasma loss and true digestion and absorption of 125I-labelled albumin in the small intestine. DM intake was depressed by parasitism, being 1331, (SE 70), 423 (SE 32) and 529 (SE 52) g/d during weeks 3, 7 and 17 respectively. The flow of nitrogen at the proximal jejunum and in faeces was increased by parasitism during week 7 and at the abomasum and ileum during week 17. Plasma protein-N loss (g/d) into the gastrointestinal tract was 0.68 (SE 0.091) and 1.97 (SE 0.139) during week 7, and 0.85 (SE 0.158) and 1.96 (SE 0.396) during week 17, in control and infected sheep respectively. True digestion and absorption of albumin in the proximal small intestine, the site of infection, was very low (mean 0.08) and was not affected by parasitism. Between the abomasum and terminal ileum absorption of albumin was high (mean 0.87) and again was not affected by parasitism. It was calculated that of the total increase in endogenous protein passing from the ileum tract as a result of infection, plasma protein comprised only a small percentage (10-36%). The major proportion of digestion and absorption of protein occurred in the distal small intestine beyond the site of infection and was not affected by infection. PMID- 1760445 TI - Effect of refeeding diets containing cottonseed flour with traces of gossypol on rat liver and testis. AB - The aim of the present work was to show that cottonseed flour introduced into rehabilitation diets is not nutritionally harmful. The cottonseed flour obtained from glandless seeds contains traces of gossypol. As gossypol is known to have pathological hepatic and testicular actions, the effects on hepatic variables and on the histological appearance of liver and testis of diets containing cottonseed flour were compared with those without cottonseed flour. Seventy growing male Wistar rats were divided into two groups. The control group (C) received a balanced diet (200 g casein + 3 g methionine/kg) for 78 d and the experimental group was fed on a low-protein diet (20 g casein + 3 g methionine/kg) for 29 d. After the period of protein deprivation, the depleted rats were divided into four groups and each group was refed with a different diet, for 49 d: a balanced diet (200 g casein + 3 g methionine/kg; rC), maize-soya-bean flour-milk (60:30:5, by wt; MSM), maize-cottonseed flour-milk (60:30:5, by wt; MCM) or rice-cottonseed flour-milk (60:30:5, by wt; RCM). Each diet was supplemented with a vitamin mixture (10 g/kg) and a salt mixture (40 g/kg). In the liver, protein, total lipid, fatty acid composition and nucleic acid contents were determined after 29 d of protein deprivation and after 2, 14, 29, 49 d of refeeding. The refeeding of rats with either diet MSM or RCM promoted a higher growth than that with diet MCM or diet rC. In all groups, a progressive decrease in relative liver weights with age was observed. The highest values were obtained with diets rC and MSM. After 49 d of refeeding, the lowest values for lipid, DNA and protein:RNA and the highest values for RNA and RNA:DNA were obtained with the cottonseed diets (MCM and RCM). Rats fed on the cottonseed-flour diets for a 49 d period after severe protein malnutrition showed no change in size or shape of their hepatocytes compared with those obtained with the control casein diet, and all stages of spermatogenesis occurred normally and spermatozoa were accurately formed. Therefore, our findings show that a low level of gossypol administrated during 49 d, even to an organism weakened by protein malnutrition, does not affect hepatic variables and the histological appearance of liver and testis. PMID- 1760446 TI - Metabolic effects of coconut, safflower, or menhaden oil feeding in lean and obese Zucker rats. AB - The aim of the present investigation was to study the effects of fish oil feeding in obese Zucker rats to establish its suitability as an animal model of hyperlipidaemia, and to understand the possible mechanism of fish oil-induced perturbations in cell metabolism. Lean and obese Zucker rats were fed on diets containing 180 g coconut, safflower, or menhaden oil/kg for 10 weeks. Body weights and food intakes of lean coconut (LC), safflower (LS), and menhaden (LM) groups were similar. Obese menhaden (OM) rats had lower food intakes and body weights compared with obese coconut (OC) and obese safflower (OS) groups, but values for all obese rats were higher than those for lean rats. Liver weights were higher in obese compared with lean rats, but on a percentage body-weight basis menhaden oil rats had higher values within genotype. Serum cholesterol and triacylglycerol levels were lower in the OM group compared with the OC and OS groups, and in the LM group compared with the LC group. Glucose and insulin levels were highest in OS rats followed by OC and OM rats and then the lean rats. Serum triiodothyronine and thyroxine were lower in OM rats compared with OC and OS rats. Liver mitochondrial state 3 rates with glutamate-malate and succinate were lower; mitochondrial beta-oxidation was unaffected and peroxisomal beta oxidation was higher in menhaden oil rats compared with both coconut and safflower oil rats. In general, consumption of menhaden oil lowered hepatic malic enzyme (EC 1.1.1.38, 1.1.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glutathione peroxidase (EC 1.11.1.9) activities and elevated long-chain fatty acyl-CoA hydrolase (EC 3.1.2.2) activity when compared with the two other diets. It is concluded that obese Zucker rats do respond like human subjects to fish oil feeding but not to vegetable oils. The hypolipidaemic effect of fish oil appears to be mediated through a lowering of lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme. PMID- 1760447 TI - Weaning food mythology. PMID- 1760448 TI - Gastroduodenal injury from nonsteroidal anti-inflammatory drugs: risk management issues. PMID- 1760449 TI - Palatability of colonic lavage solution is improved by the addition of artificially sweetened flavored drink mixes. AB - A frequent complaint of patients asked to drink polyethylene glycol (PEG) colonic lavage solution is the salty flavor. This often results in failure to ingest the entire 4 liters of the solution and compromises bowel cleansing. The purpose of this study was to determine systematically whether the addition of a flavored drink mix sweetened with aspartame to the PEG lavage solution would improve palatability without significantly altering the osmolality of the solution. Eighty-seven (87) staff volunteers participated in a taste test of PEG lavage solutions containing varying amounts of commercially available drink mixes. The solution containing two packages of lemon-flavored KoolAid drink mix sweetened with aspartame was significantly more palatable than the others (p less than 0.005), while osmolality remained within the range specified by the manufacturer of Colyte. PMID- 1760450 TI - Alpha 1-antitrypsin deficiency. AB - alpha 1-Antitrypsin (AAT) is a polymorphic protein with many variants collectively known as the Pi system. The most common alleles are the M, S and Z, which are co-dominantly inherited. Infants with PiZZ have approximately 16% of the normal AAT serum concentration. alpha 1-Antitrypsin deficiency (AATD) is an inborn error of metabolism which is principally associated with liver disease in children and emphysema in young adulthood. Individuals with AATD produce an abnormal protein which accumulates in the liver, resulting in decreased serum levels. Affected individuals cannot protect their lungs from digestion by elastase. Smoking is a significant risk factor for the early development of emphysema. Prolastin, human alpha 1-protease inhibitor, is now available as replacement therapy. Weekly intravenous administration, with the goal of maintaining the serum AAT greater than 80 mg/dl, appears to arrest pulmonary damage. Its effect on liver disease is unknown at this time. A recombinant alpha 1-protease inhibitor is being tested in aerosol form with promising early results. PMID- 1760451 TI - Dipentum (olsalazine sodium) AB - Dipentum (olsalazine sodium), a product by Pharmacia, represents the first oral delivery of sulfa-free 5-aminosalicylic acid therapy available for remission maintenance in sulfasalazineintolerant patients with ulcerative colitis. It provides a safe and well-tolerated treatment regimen that has been shown to be as effective as sulfasalazine in maintaining remission of ulcerative colitis. PMID- 1760452 TI - Managing patient education: a perspective for the 1990s. AB - Changes in the delivery and complexity of health care make it imperative that the patient and family are provided with the information needed to make intelligent decisions and choices about health care alternatives. The intent of this paper is to outline the nurse manager's responsibilities for patient education and to provide a practical framework by which to structure patient teaching programs. Although the philosophies of self-care and self-determination are outlined and provide the primary orientation to the concept of patient education, the description of the nurse manager's clinical and aggregate skills provide both the training and practice guidelines. PMID- 1760453 TI - Standards documentation. PMID- 1760454 TI - Hospital marketing: a new frontier. AB - Competition is now forcing hospitals to become more efficient and market-wise. This article investigates the past, present and future trends in hospital marketing. Dramatic changes are taking place at a staggering pace in the health care arena. An understanding of the necessity of hospital marketing is essential for all health care workers. PMID- 1760455 TI - Why an international gastroenterology nursing organization? PMID- 1760456 TI - Health care trends for older people. AB - Research is showing us a radically different view of aging from the one seen by earlier generations. Attitudes, which were based on the myth that physical and mental decline are inevitable with age, are beginning to change as a result of new scientific information. What we are learning is that aging involves both intrinsic and extrinsic factors. The universal phenomena that occur in all of us as we advance in age are intrinsic characteristics of aging, while extrinsic factors are those characteristics that can be prevented or modified, such as lifestyle choices, environmental exposure, and disease. PMID- 1760457 TI - Prevalent sleep problems in the aged. AB - Quality of sleep influences the level of daytime functioning, including stress levels, psychosomatic complaints, general health, and overall well-being. As people age, they complain more about disturbed sleep, insomnia, increased time in bed, and sleep fragmentation. These complaints can be related to circadian rhythm desynchronization, hypnotic or other medication use, chronic bedrest, napping, dementia, or to sleep apnea, a disorder of respiratory cessation which is quite prevalent in the elderly. We review here the results of 12 years of research on sleep in the elderly. In studies of three populations of elderly, it was found that between 24% and 42% had five or more apneas per hour of sleep and 4%-14% had 20 or more apneas per hour of sleep. Since apnea is related to dementia and even to mortality, this high prevalence of apnea is of extreme importance. PMID- 1760458 TI - Biofeedback-assisted relaxation training for the aging chronic pain patient. AB - The older segments of the U.S. population are expanding rapidly and account for a disproportionate amount of health care, including treatment for pain-related musculoskeletal disorders. In a prospective study with objective measures and one year follow-up, Middaugh et al. (1988) found that older patients (55-78 yr; N = 17, 76% success) treated in a multidisciplinary chronic pain rehabilitation program enjoyed a success rate equal to that of younger patients (29-48 yr, N = 20, 70% success). The current study presents additional data on these two groups of patients to compare their ability to learn the physiological self-regulation skills taught in the biofeedback/relaxation component of the multimodal program. This component included progressive muscle relaxation training, diaphragmatic breathing instruction, and EMG biofeedback. Repeated measures ANOVA showed significant increases in digital skin temperature (peripheral vasodilation) and decreases in respiration rate both within and across training sessions (p values = .04 to .0001) with no differences between age groups (p greater than .05). EMG measures for the upper trapezius ms in patients with cervical pain showed similar deficits in muscle control at evaluation and similar improvements with biofeedback training for the two age groups. These findings indicate that older pain patients responded well to the biofeedback/relaxation training component of the multimodal pain program. PMID- 1760459 TI - Electromyographic biofeedback training for tension headache in the elderly: a prospective study. AB - This study evaluated the effects of a 12-session frontal electromyographic biofeedback training regimen on the headache activity of eight tension headache sufferers aged 62 and older. The biofeedback sessions were slightly modified for a geriatric population, essentially to increase comprehension and retention of rationale and instructions. Post-treatment assessment at three months revealed significant decreases in overall headache activity (50% or greater) in 50% of the subjects, and moderate improvement (35%-45%) in three of the remaining four subjects. Significant clinical and/or statistical pre-post differences were also found for the number of headache-free days, peak headache activity, and medication index. This is the first prospective study of biofeedback training for tension headache in an elderly population and, unlike previous retrospective studies, suggests that such therapy may be an effective intervention in the treatment of tension headaches in the elderly. PMID- 1760460 TI - The present and future roles of biofeedback in successful aging. AB - Brief descriptions of the applications of biofeedback in normal elderly and in diseases occurring during old age are given. An outline for new applications or expansion of areas presently under investigation is presented. PMID- 1760461 TI - Sustained effects of biofeedback-assisted relaxation therapy in essential hypertension. AB - The usefulness of biofeedback-assisted relaxation as an adjunct or substitute for pharmacotherapy in essential hypertension can be enhanced if the effects are shown to persist after formal treatment has ended. Patients with essential hypertension successfully treated with biofeedback-assisted relaxation were recalled for follow-up yearly after the termination of treatment. Twenty-six of 40 patients met the BP criterion for success. At one-, two-, and three-year follow-up, 31%, 38%, and 27% of the successful completers continued to meet the criterion for success. The pretreatment-posttreatment decreases in BP were accompanied by decreases in forehead muscle tension and urinary cortisol. Forehead muscle tension, urinary cortisol, and anxiety levels were significantly lower than pretreatment one year after the end of treatment. Self-report data were used to assess continued relaxation practice. No relationship was found between practice and any other dependent measure. It appears that some patients trained in biofeedback-assisted relaxation can maintain lowered blood pressure, muscle tension, anxiety, and cortisol levels over the long term; however, the role of relaxation practice in maintaining these lowered levels remains unclear. PMID- 1760462 TI - EMG biofeedback treatment of torticollis: a controlled outcome study. AB - Successful treatment of torticollis with electromyographic (EMG) biofeedback has been reported in a number of single case and single group studies. The present investigation represents the first controlled outcome study. Twelve torticollis patients were randomly assigned to EMG biofeedback or relaxation training and graded neck exercises (RGP). The procedure involved three sessions of baseline assessment, 15 sessions of EMG BF or RGP, 6 sessions of EMG BF or RGP plus home management, 6 sessions of home-management alone, and follow-up 3 months after the end of treatment. A variety of outcome measures were used including physiological (EMG from the two sternocleidomastoid muscles, skin conductance level), behavioral (angle of head deviation, range of movement of the head), and self report (depression, functional disability, body concept), therapist and "significant other" reports and independent observer assessment of videos. In both groups, neck muscle activity was reduced from pre- to posttreatment. This reduction was greater in the EMG biofeedback group. There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group. Therefore, the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects. Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of "arousal." Significant improvements of extent of head deviation, and range of movement of the head, as well as reductions of depression were present, which were not different in the two groups. At the end of treatment, no patient was asymptomatic. Any therapeutic benefit was generally maintained at follow-up. The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one. Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger samples are required. PMID- 1760463 TI - The psychophysiology of motor vehicle accident related posttraumatic stress disorder. AB - Heart rate, BP, and electrodermal responses of four individuals with PTSD secondary to motor vehicle accidents (MVAs) were measured while they imagined two separate scenes related to their MVA. Results showed reliable HR responses to these images. In addition, SBP and DBP also showed some responsivity to the images while skin resistance level changed reliably in only 2 of 4 subjects. Psychophysiological measurement could play a role in the assessment and treatment of MVA-related PTSD. PMID- 1760464 TI - Distribution of indole-producing urease-negative pasteurellas in animals. AB - Three hundred fifty-six animal isolates of indole-positive urease-negative cultures of Pasteurella, which would formerly have been classified as P. multocida, were examined with respect to their relationship to the recently described P. multocida subspecies (ssp.) multocida, septica, and gallicida and P. canis, P. stomatis/Taxon 16, and Pasteurella sp. B. Two hundred sixty-three (73.9%) of the cultures could be identified with one of these taxa, and 93 isolates (26.1%), representing 17 different biotypes, were unassignable. Pasteurella multocida ssp. multocida was the predominant taxon throughout and in most of the 25 animal species from which isolations were made. In dogs, P. canis was the most frequent. Different degrees of host predilection were observed also in P. multocida ssp. septica for cats, P. canis for sheep, and 2 of the unassignable biotypes for cattle and dogs, respectively. Overall, the respiratory tract was the most frequent source of isolates, but a propensity of P. multocida ssp. septica for localization in the central nervous system of cats was noted. PMID- 1760465 TI - Association of a Pasteurella haemolytica-like organism with enteritis in swine. AB - A Pasteurella haemolytica-like organism was isolated from the intestines of 28 swine with clinical, gross, or microscopic evidence of enteritis. In 15 cases, other known enteric pathogens were also demonstrated, and in 13 cases, no other pathogens were detected. The mean age of affected animals was 44 days. Most of the animals had clinical evidence of diarrhea. Gross enteric lesions were present in 17 of 21 cases. Microscopic lesions were present in 24 of 26 cases. A diffuse or segmental moderate to severe necrotizing enteritis was the most common lesion in cases in which only the Pasteurella haemolytica-like organism was isolated. Biochemical tests gave results consistent with Pasteurella haemolytica, and 5 of 15 isolates met criteria for biotype A. Negative results were found with an indirect haemagglutination procedure for P. haemolytica. PMID- 1760466 TI - Light and electron microscopic observations of a segmented filamentous bacterium attached to the mucosa of the terminal ileum of pigs. AB - Segmented filamentous bacteria were seen attached to apical villous enterocytes of the terminal ileum in 15 of 2,766 live pigs submitted for necropsy over a 6 year period. Infected pigs ranged in age from 2 to 13 weeks. All pigs except 2, however, were greater than 4 weeks old and had been weaned. All infected pigs came from conventional commercial herds with intensive, all-indoor, confinement rearing management systems. The bacteria were gram negative or gram variable and were not associated with any clinical disease. Bacteria were more commonly attached to epithelium on the dome villi in the ileum. Electron microscopic examination revealed organisms composed of a cranial segment with a nipple-like appendage and several other segments making up elongated filaments of various lengths. Each filament was divided into segments by transverse septa. The nipple like appendage served as an attachment apparatus by indenting the enterocyte surface without physically penetrating it. Occasionally, the colonizing bacterium was itself colonized by small rod-shaped bacteria that completely surrounded the filament. PMID- 1760467 TI - Patterns of bovine dairy submissions to the California Veterinary Diagnostic Laboratory System. AB - Dairy cattle submissions to the California Veterinary Diagnostic Laboratory System (CVDLS) were analyzed to determine submitter statistics. Eligible submissions were those received July 1, 1987 through December 31, 1989 for reasons other than regulatory brucellosis serology. A comprehensive list frame of California dairies was constructed from Brucella Ring Test information and served as the comparison population for the study. Analyses were performed based on geographic location, herd size, proximity to a CVDLS laboratory, and frequency of submission. Thirty-nine percent of the 2,490 California dairies in the reference population had submitted specimens greater than or equal to 1 time to the CVDLS during the study period. Twenty-three percent of the reference population had submitted greater than or equal to 2 times. Specimens were more likely to be submitted from larger herds than smaller herds. Larger dairies also submitted specimens more frequently. Dairies in the northern part of the state were more likely to submit specimens and submitted more frequently than southern herds when herd size was accounted for in the analysis. Mean submission rate (+/- SD) for the 970 submitting dairies was 1.4 (+/- 1.8) submissions/year. Forty-six percent of the dairies accounted for 80% of submissions, whereas only 14% of dairies accounted for 50% of all diagnostic dairy submissions. PMID- 1760468 TI - Identification of porcine mycoplasmas using commercial enzyme assay systems. PMID- 1760469 TI - Pseudospirochetes in animal blood being cultured for Borrelia burgdorferi. PMID- 1760470 TI - An Eperythrozoon-like parasite of llamas: attempted transmission to swine, sheep, and cats. PMID- 1760471 TI - Fatal reactions in bison following systemic organophosphate treatment for the control of Hypoderma bovis. PMID- 1760472 TI - Analysis of corn and cultured corn for fumonisin B1 by HPLC and GC/MS by four laboratories. PMID- 1760473 TI - Encephalitis in two porcupines due to Baylisascaris larval migration. PMID- 1760474 TI - Epizootics of diaphragmatic hernias in swine. PMID- 1760475 TI - Posterior paralysis and electrocution of swine caused by accidental electric shock. PMID- 1760476 TI - Cultivation of Mycobacterium paratuberculosis from bovine fecal specimens and a suggested standardized procedure. PMID- 1760477 TI - Ruminant paratuberculosis--a century of progress and frustration. PMID- 1760478 TI - [Artificial nutrition in kidney failure]. AB - Renal failure in itself generates a state of malnutrition, due to three main causes: inadequate ingestion (anorexia, vomiting or diet insufficiencies), the existence of catabolic factors (proteins, acidosis, PTH) and extrarenal depuration (which provokes a lack of amino acids and vitamins). Artificial nutrition constitutes a series of measures that can be adopted to act upon each of the above causes. Adequate ingestion compared to inadequate ingestion can be performed orally (especially in chronic renal failure) by parenteral administration (preferable in acute renal failure) and enteral administration (complementary in both cases). The quantity and quality of adequate nutrients is non-dependent on the method of administration; 500 ml, of water should be administered plus diuresis, plus loss from other tracts; the mineral intake of sodium, potassium and phosphorus should be restricted; in the case of vitamins, these should be administered, especially the B and D complexes; there should be sufficient calories to constitute a hypercaloric diet (from 30-50 kg/day), at least 50% in the form of carbohydrates (hypertonic glucose, if administered intravenously, and dextrinolmaltose or starch if administered through the digestive tract) and at least 40% in the form of lipids (preferably of vegetable origin, rich in non-saturated fatty acids); proteins are the mainstay of nutrition in renal failure; thus, with a normal renal function or in dialysis, a dose of 1 g/kg/day is recommended; in chronic renal failure, 0.5 g/kg/day; in cases of renal failure not on dialysis, 0.3 g/kg/day, supplemented by essential amino acids or cetoacids (the effectiveness of the latter is still in dispute).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760479 TI - [Informatics and parenteral and enteral nutrition: the state of the art]. AB - A review was performed of the progress made with the assistance of computers in the parenteral and enteral nutrition field as one more of the many uses made today of the computer industry. Detailed analysis is presented by the authors of the different types of hardware used, as well as the main characteristics and content of the programmes and applications existing in this field, both restricted to small working groups and in management. A comparative study was also made of the management programmes distributed free of charge by some laboratories. Finally, an evaluation was made of the advantages and disadvantages of using computers in parenteral and enteral nutrition at present. PMID- 1760480 TI - [A prospective study of the functioning of 2 types of enteral nutrition catheters]. AB - The problems of disintubation and obstruction of nutritional catheters are common during treatment with enteral nutrition. This prospective study has been designed to evaluate the differences in the frequency of obstruction between two different types of enteral nutrition catheter. Catheter A (Silk, Ibys) with one single lateral outlet, wide, long and with a curved edge, and Catheter B (Nutrisoft M, Kabi-Pfrimmer), with several smaller lateral holes, 46 nutritional periods were studied, divided into two groups: first group, n = 32 (catheter A) and second group n = 14 (catheter B, Nutrisoft M, Kabi-Pfrimmer). There were no significant differences between both groups for the type of diet administered, osmolarity, speed, volume administered, number and duration of interruptions, external fixation, washing of the catheter and duration of the nutritional period. The catheter slipped out in 21 periods (46%). Obstruction of the catheter was the cause of disintubation of the catheter in eight cases, five of the cases with catheter A (15%) and three cases with catheter B (21%); there were no significant differences between the values for both. These results indicate that the frequency of obstruction is similar with both catheters; however, the Silk catheter may have a better tolerance and be easier to intubate, due to its smaller external diameter. PMID- 1760481 TI - [The protocolization and follow-up of enteral nutrition. 2 years of experience]. AB - The Artificial Nutrition Unit was set up in 1980 in the Pharmacy Service, with the objective of preparing parenteral nutritional units. Different protocols were prepared, approved by the Commission of Pharmacy and Therapeutics. From 1986 onwards, follow-up was commenced and since March 1988, nutritional evaluation of the patients on enteral nutrition has been performed. Encouraged by the results obtained, a proposal for protocolizing enteral nutrition was put to the Commission of Pharmacy and Therapeutics, which was approved in December 1988. The main objective was to select the enteral diets which would be used as a formula for existing hospital diets and, after establishing this formula, protocolize the indications that would assists in selecting from among the diets available, the ones that would best adapt to the individual needs of each patient. As a secondary objective, the Artificial Nutrition Unit took on the responsibility of processing the medical instructions and dispensing enteral diets using the dosage/patient/day distribution system. It also provides information to medical and nursing staff on existing diets, as well as on rules for administration and storage in nursing units, providing when necessary the most suitable containers, equipment and pumps for administering the diets. It also carries out a nutritional evaluation of patients exclusively on enteral nutrition, as well as follow-up of these. Finally, it prepares the monthly actual cost figures generated by each nursing unit, since diets not administered after twenty-four hours are returned to the Nutrition Unit. One problem existing is the non administration of products or patients who refuse to take their diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760482 TI - [The quality control of a photoprotector bag against ultraviolet light]. AB - The action of light on parenteral nutritional solutions may affect the stability of many of their ingredients. The aim of this study is to perform quality controls on a commercial photoprotective bag by quantifying the degradation of riboflavin in isotonic saline solution during forty-eight hours. Thirty solutions were prepared using 5 mg of riboflavin in 500 ml of saline solution. These were divided into three batches; one not protected from the light, one in a black bag and the third in a commercial bag. Samples were taken at 0 and 48 hours, and were analyzed by spectrophotometry. Solutions were prepared using 1.75 mg of riboflavin in 500 ml of saline solution. The same method was followed, and the samples were analyzed by fluorometry. The results were analyzed using the Student t test. The black bag was seen to be superior to the other two as a protector against ultraviolet light. There were no significant differences between the commercial bag and the non-protective bag. PMID- 1760483 TI - [The effect of nutrition on bone marrow transplantation]. AB - Malnutrition alone may provoke considerable immune alterations, mainly in the immunocellular function, and in particular in the T lymphocyte and macrophage monocytic function. This gives rise to an increase in proneness to infections, which in patients subjected to bone marrow transplants, will be increased by the intense neutropenia suffered by them. This study shows the greater incidence of infection among badly nourished patients compared to nourished patients. It was also observed that short bouts of high temperature mainly occurred in a subgroup of patients with an acceptable nutritional level, which in our opinion was the cause for none of them developing the infectious illness. Finally, one of the germs most often found in these patients is Staphylococcus epidermis, and the most common method of entry is through the catheters used in the administration of medicines and artificial nutrition. Emphasis is placed on the role played by nursing in preventing this type of infection. PMID- 1760484 TI - High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. AB - Determination of homocysteine in plasma or serum for evaluation of cobalamin and folate deficiency is becoming an important diagnostic procedure. Accurate, rapid and low cost methods for measuring homocysteine are therefore required. We have improved an HPLC method and made it suitable for clinical application. The more important changes are the addition of an internal standard, mercaptopropionylglycine, and the use of a plasma/serum based calibration material. The method consists of the following steps: reduction of the sample with tri-n-butylphosphine, precipitation of proteins, derivatisation with ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate, and HPLC separation followed by fluorescence detection. The linearity of the assays is established and the coefficient of variation is 3.0%. Stability studies show that blood samples must be cooled or centrifuged immediately after venipuncture. The method is useful for evaluation of cobalamin or folate deficiency, especially in patients with normal or moderately depressed cobalamin or folate concentrations in blood. PMID- 1760485 TI - Mathematical modelling of competitive labelled-ligand assay systems. Theoretical re-evaluation of optimum assay conditions and precision data for some experimentally established radioimmunoassay systems. AB - A mathematical theory of competitive labelled-ligand assays was developed with the intention of theoretically re-evaluating the optimal assay conditions and precision data of assay systems established by experiment. Our theory is based upon the assumptions of a simple bimolecular reaction mechanism, homogeneous reactants, as well as kinetically indistinguishable labelled and non-labelled ligands. The general case of two-step (non-equilibrium) assay was considered including the one-step (equilibrium) assay as a special case. The solution of the system of corresponding kinetic differential equations was used to mathematically construct standard curves. Furthermore, intraassay precision profiles and indices as well as detection limits were calculated considering solely the pipetting error, epsilon, as a source of experimental error. A procedure was outlined to mathematically determine the optimal incubation conditions for any assay system targeted to a given analyte concentration, P, at which the standard deviation of assay results is to be minimized. Estimates of both the content of binding sites and the equilibrium constant, K, of the specific binding agent are necessary, and these can be derived from Scatchard plots. For six RIA systems, of which three were one-step and three were two-step assays, experimental assay conditions and precision data were compared with theoretical predictions. Experimentally determined antibody binding site concentrations agreed fairly well with those independently evaluated by mathematical optimization. Mean precision indices, defined as constituting an average over the complete precision profile, were found to be within the theoretically predicted range, i.e. two- to threefold the pipetting error.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760486 TI - A fluorometric enzyme immunoassay for follitropin and lutropin. AB - The analytical performance of the Stratus (Baxter) automatic analyser for human lutropin and follitropin determination was evaluated and compared with that of an immunoradiometric assay. Within-run and between-run imprecision were lower than those of the immunoradiometric assay. No significant differences were obtained in the parallelism study. A good and significant correlation was obtained between both methods. Results obtained for both methods were not interchangeable. The Stratus automatic analyser can replace radioisotopic methods, thus eliminating radioactive hazards. PMID- 1760487 TI - Evaluation of the measurement of prolactin in serum with Enzymun-Test System ES 600. AB - The Enzymun-Test System ES-600 is a fully automated analyser for the Clinical Chemistry hormone laboratory. The Enzymun-Test prolactin, an enzyme immunoassay, is based on a sandwich technique using two monoclonal antibodies, one coated onto tubes and the other labelled with peroxidase. We have studied the measurement of prolactin concentration in serum and compared the results obtained with both this system and with the manual IRMA used in our laboratory. The within-day imprecision gave the following CV (n = 20): 6% at 64 mU/l, 1% at 379 mU/l and 2% at 1232.1 mU/l. The CV for between-day imprecision (n = 20) was 10%, 8% and 6%, respectively. The detection limit was 4 mU/l and linearity was demonstrated with geometric dilutions of a highly concentrated serum. We observed an average recovery of 104%, ranging 95.6%-110%. The calculated carryover was of 0.05%, and there was no trend in the measurements to indicate the occurrence of long series drift. In the study of interchangeability (Passing-Bablok regression test) we obtained a linear equation: y (ES-600) = 3.16 mU/l + 0.82 x (IRMA), with the confidence intervals (95%) a(-30.69, 21.53); b(0.73, 0.99); and a correlation coefficient of r = 0.98. PMID- 1760488 TI - International Union of Pure and Applied Chemistry, Commission on Analytical Nomenclature and Clinical Chemistry Division. Nomenclature for automated and mechanised analysis, (recommendations 1989). PMID- 1760489 TI - Gastrointestinal surgery for severe obesity. AB - The National Institutes of Health Consensus Development Conference on Gastrointestinal Surgery for Severe Obesity brought together surgeons, gastroenterologists, endocrinologists, psychiatrists, nutritionists, and other health care professionals as well as the public to address: the nonsurgical treatment options for severe obesity, the surgical treatments for severe obesity and the criteria for selection, the efficacy and risks of surgical treatments for severe obesity, and the need for future research on and epidemiological evaluation of these therapies. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) patients seeking therapy for severe obesity for the first time should be considered for treatment in a nonsurgical program with integrated components of a dietary regimen, appropriate exercise, and behavioral modification and support, (2) gastric restrictive or bypass procedures could be considered for well informed and motivated patients with acceptable operative risks, (3) patients who are candidates for surgical procedures should be selected carefully after evaluation by a multidisciplinary team with medical, surgical, psychiatric, and nutritional expertise, (4) the operation be performed by a surgeon substantially experienced with the appropriate procedures and working in a clinical setting with adequate support for all aspects of management and assessment, and (5) lifelong medical surveillance after surgical therapy is a necessity. The full text of the consensus panel's statement follows. PMID- 1760490 TI - Assessment of histocompatibility of different hemoglobin solutions using mesenteric perfusion on the small bowel of the male Wistar rat. AB - Histocompatibility assessment of 70 g/l stroma-free hemoglobin solutions pyridoxylated or not, and purified or not, was carried out using vascular perfusion of the intestine of rats. Mechanical and ultrastructural changes in the organ and the arteriovenous difference of PO2 were compared to those obtained with albumin, gelatin and dextran. Overlapping epithelium conserves its structure in the presence of hemoglobin, whereas it is partially or totally destroyed with the plasma substitutes. Nevertheless, with non pyridoxylated hemoglobin there is a strong detachment of the epithelium from the lamina propria. The intestine, irrigated by the hemoglobin solutions shows efficient peristalsis, but this totally disappears with plasma substitutes. For similar arterial PO2, for all the solutions, the arteriovenous difference was of 100 mmHg for the hemoglobin solutions, whereas they never exceeded 60 mmHg for the plasma substitutes. Hemoglobin pyridoxylation led to an arteriovenous difference significantly superior (p less than 0.001) to those obtained using non modified hemoglobin. With their O2 supply hemoglobin solutions appear able to limit the development of hypoxia in the tissue. The continuation of peristalsis and the weak ultrastructural modifications confirm the slight histological improvement gained when using pyridoxylated hemoglobin. Nevertheless an extravasation appeared constantly, as well as flow reduction during perfusion with the hemoglobin solutions. PMID- 1760491 TI - Effects of hepatic stimulatory factor released from free or microencapsulated hepatocytes on galactosamine induced fulminant hepatic failure animal model. AB - This paper describes the presence of a cell free hepatocyte stimulating factor secreted by hepatocyte cultures. Hepatocytes were isolated from 70-90 grams Wistar-Lewis rats. Free or microencapsulated hepatocytes in alginate matrix were cultured separately. Cell free supernatant was collected from the culture medium in which was cultured free hepatocytes; microencapsulated hepatocytes or control microcapsules containing no microcapsules. This was tested in the galactosamine rats. A galactosamine dose of 2.7 g/Kg of body weight given intraperitoneally to Wistar-Lewis rats resulted in reproducible hepatic necrosis with 90% mortality. Cell free supernatant from one day old free hepatocyte cultures was able to increase survival time and incorporation of 3H-thymidine in liver of galactosamine induced fulminant hepatic failure rats at the time of maximal liver damage. The cell free supernatant of one day old microencapsulated hepatocyte cultures did not have the same stimulatory effect either on survival time or incorporation of thymidine. Another study was carried out as follows. The microcapsules containing hepatocytes were ruptured. The supernatant of the microcapsule contents was collected. This was found to have hepatic stimulatory effect as shown by survival time and incorporation of thymidine. This suggests that hepatocytes are a source of a factor(s) which is capable of stimulating liver regeneration in the galactosamine induced fulminant hepatic failure rats at the time of maximal liver damage. Since the molecular weight cut off of this particular preparation of microcapsule is molecular larger than albumin, this suggests that the molecular weight of this factor is in the macromolecular range. PMID- 1760492 TI - Physicochemical characteristics of hepatic stimulatory factor prepared from cell free supernatant of hepatocyte cultures. AB - We previously reported that the cell free supernatant of hepatocyte cultures contained a hepatic stimulatory factor, which increases survival time and stimulates liver regeneration in the galactosamine induced fulminant hepatic failure animal model. When hepatocytes were microencapsulated in an alginate matrix, the cell free supernatant outside the microcapsuled lacked the above stimulatory effects. However, the cell free content of microcapsules was able to increase both survival time and incorporation of 3H-thymidine in our animal model. This hepatic stimulatory factor has a molecular weight greater than albumin because alginate microcapsules allow the penetration of albumin but not the hepatic stimulatory factor. In this paper we report the molecular weight study and some other physiochemical characteristics of this factor. Using Sephacryl gel chromatography we showed that this factor has a molecular weight of over 110,000 D. This factor loses its hepatic stimulatory effect after heat or trypsin treatment. Although its elution profile on Sephacryl gel does not change after such treatments. PMID- 1760493 TI - Surface modification of corneal contact lens with phosphoryl choline by glow discharge. AB - Polymers like poly(methylmethacrylate) (PMMA) and poly(2 hydroxyethylmethacrylate) (PHEMA) are widely used in the development of hard and soft contact lenses. Cell adhesion and deposition of chemicals such as calcium, lipoproteins and mucin on the lens surface cause visual acuity which is the main problem in extended uses of contact ocular lenses. In order to minimise the cell adhesion and other type of depositions, a method of surface modification of lens involving the use of phosphoryl choline, a phospholipid and the glow discharge technique has been described. The power variation of the lenses after modification has been checked using Topcon lensometer. The possible power changes of the modified samples due to the exposure to the normal light in the laboratory, darkness, ultraviolet (U.V.) light or saline have been investigated by taking the visible and ultra violet spectra using Beckman spectrophotometer. Surface energy variations after modifications of the samples have been checked by sessile drop water contact angle measurements. Glow discharge treatment increases the hydrophilicity of the samples. It seems, the modifications do not affect the power of hard contact lens significantly. It is also observed that the exposure of samples to the normal light in the laboratory, darkness, U.V. light or saline make no significant change in the visible and ultraviolet spectra of the samples before and after modification. PMID- 1760494 TI - Effect of stabilization temperature on the degradation of adriamycin in albumin microspheres. AB - The effect of stabilization temperature on the degradation of adriamycin HCl during the preparation of albumin microspheres was investigated. The degradation of adriamycin HCl by heating at various temperature with different time interval in dried adriamycin HCl powder, adriamycin HCl aqueous solution, wetted Adriablastina (adriamycin HCl with lactose) powder and Adriablastina aqueous solution was also studied. In the presence of water the degradation of adriamycin HCl was found; whereas, in the absence of water no degradation occurred. The degradation of adriamycin HCl in solution and wetted powder showed a zero order reaction. An increase in temperature increased degradation rate. The rate constant for adriamycin HCl degradation in Adriablastina solution obtained was in good agreement with that in adriamycin HCl solution. It was suggested that the presence of lactose had no interference in the degradation of adriamycin HCl. The zero-order reaction of degradation was attributed to the drug behaved like a suspension. The degradation of adriamycin HCl at various stabilization temperature during the preparation of microspheres had the same tendency as those of the adriamycin HCl solution and the wetted adriamycin HCl powder that were heated by the DSC instrument with the condition similar to the preparation of microspheres. PMID- 1760495 TI - Antibacterial multifilament nylon sutures. AB - Multifilament nylon fibers were made antibacterial by dopping with iodine. Nylon fibers were immersed in acetone solution of iodine for 48 hours at room temperature for dopping of iodine. It was observed that iodine uptake by the nylon fibers increased with the increase in concentration of iodine in the solution. Antibacterial activity of these iodine dopped samples was evaluated by measuring the zone of inhibition. The bacterial species used for this study were Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae. Iodine dopped fibers exhibited good antibacterial activity against these bacterial species. Release of iodine in distilled water is sustained for about 30 days. Antibacterial activity of the fibers decreases with the release of iodine in water. Ultra-violet and visible spectroscopic studies showed that tri iodide ions were released from the dopped samples in the aqueous medium. These I3 ions might be responsible for the observed antibacterial activity. Fiber shrinks on iodine dopping leading to increase in the denier of the fiber. However effect of iodine dopping on the breaking load of fibers is not significant. PMID- 1760496 TI - Polyether urethane urea membrane for an improved hemodialysis. AB - This paper reviews our current activities of developing polyether urethane urea membranes for hemodialysis application. It is observed that the processing parameters such as precipitation medium, precipitation temperature etc. can influence the porosity of the membrane and subsequently the permeability property. Polyurethane/poly(methyl methacrylate) blended membranes have also shown high permeability. All the membranes are subjected to different sterilization processes and the pore sizes before and after sterilization are determined. The changes in the pore size due to sterilization seems to effect the permeability. PMID- 1760497 TI - Endogenous chelation of exogenous aluminum in renal patients--a factor in aluminum toxicity? PMID- 1760498 TI - Compatibility of biomaterials with blood. PMID- 1760499 TI - Gel-liquid crystalline transition of some multilamellar lipid bilayers follows classical kinetics with a fractional dimensionality of approximately two. AB - The relaxation kinetics of the gel-liquid crystalline transition of phosphatidylcholine (DC14PC, DC16PC, and DC18PC) multilamellar vesicles have been examined using volume-perturbation calorimetry. The time-dependent temperature and pressure changes associated with a periodic volume perturbation are monitored in real time. Data collected in the time domain are transformed to the frequency domain using Fourier series representations of the perturbation and response functions. Because a very small perturbation is imposed during the experiment, linear response theory is suitable for analysis of the relaxation process. The Laplace transform of the classical Kolmogorov-Avrami relation of transition kinetics is used to describe the dynamic response in the frequency domain. For DC14PC and DC16PC, the relaxation process is better fit with an effective dimensionality of n = 2 rather than n = 1. For DC18PC, we estimate that an effective dimensionality of approximately 1.5 will best fit the data. These results indicate that the gel-liquid crystalline transition of these lipid bilayers follows the classical Kolmogorov-Avrami kinetic model with an effective dimensionality greater than 1 and the assumption of simple exponential decay (n = 1) commonly used in data analysis may not always be valid for lipid transitions. Insofar as the dimensionality of the relaxation reflects the geometry of fluctuating lipid clusters, this parameter may be useful in connecting experimental thermodynamic and kinetic results with those obtained from Monte Carlo simulations. PMID- 1760500 TI - Kinetic constants of the acetylcholine (ACh) receptor reaction deduced from the rise in open probability after steps in ACh concentration. AB - Outside-out patches of enzymatically dissociated adult and denervated mouse muscle fibers were superfused repetitively by pulses of acetylcholine (ACh) containing solution. Up to 300 channels opened simultaneously 300 microseconds after the beginning of a 1,000 microM ACh pulse corresponding to a peak current i of almost -1 nA. Single responses to ACh were averaged and the concentration dependence of i and of the rise time tr from 0.1 i to 0.9 i was measured. In adult receptors, i increased proportional to the second to third power of ACh concentration, whereas in embryonic-type receptors it was proportional to the first to the second power. tr increased from approximately 0.3 ms at 1,000 microM ACh to a plateau value of approximately 5 ms for adult and of approximately 10 ms for embryoniclike receptors at concentrations less than 10 microM ACh. The concentration dependence of i and tr was simulated using the standard model of ACh binding with different combinations of rate constants and two and three binding sites for ACh. The calculated curves were compared to the measurements and a set of well fitting rate constants was determined for adult and embryoniclike receptors. Three binding sites for ACh were necessary to fit the dose response for i for adult receptors. A method for deriving rate constants in a model of ACh-receptor interaction is described that avoids analysis of open closed kinetics of single channels, which in rapid systems, as the ones studied here, are at the limit of the frequency response of the current measurement. PMID- 1760501 TI - Coupling of spectrin and polylysine to phospholipid monolayers studied by specular reflection of neutrons. AB - The technique of specular reflection of neutrons is applied for the first time to study the charge-dependent interaction of the protein spectrin and the polypeptide poly-L-lysine with model phospholipid monolayers in the condensed phase state. We first established the structure of a pure monolayer of dimyristolyphosphatidylcholine (DMPC) in both the expanded and condensed fluid phase states without protein in the subphase. The thickness of the hydrocarbon chains increases from 11.4 +/- 1.5 A in the expanded state to 15.8 +/- 1.5 A in the condensed state, whereas the head group region is approximately 10 A thick for both phase states. When spectrin is present in the subphase, the dimensions of DMPC in the condensed state are not significantly affected, but there is approximately 0.09 volume fraction spectrin in the head group region. Lipid spectrin coupling is enhanced by electrostatic interaction, as the volume fraction of spectrin in the head group region increases to 0.22 in a mixed monolayer of DMPC and negatively charged dimyristolyphosphatidylglycerol in the condensed state. In contrast to spectrin, polylysine does not penetrate the head group region, but forms a layer electrostatically adsorbed to the charged head groups. PMID- 1760502 TI - Evidence that the spectrin network and a nonosmotic force control the fusion product morphology in electrofused erythrocyte ghosts. AB - The conversion of the membrane area in the "contact zones" shared by erythrocyte ghosts held in contact by dielectrophoresis into a fusion product by electrofusion was studied by both light and electron microscopy. Fusion products fell into two categories: (a) those with a freely expanding open lumen which ended in the "giant cell morphology" and with considerable internal vesicle membrane fragments, and (b) linear chains of polyghosts with long term stability but having planar diaphragms at the ghost-ghost junctions. Thin section electron microscopy showed each of these planar diaphragms to be a double membrane septum multiply-perforated with fusion pores. Heat and low ionic strength treatments known to denature or detach spectrin caused the stable planar diaphragms to dissolve, thereby quickly converting the polyghost chains to the giant cell morphology, thereby suggesting that spectrin restricts fusion zone diameter expansion if it is intact. Other indications suggest that the expansion of the open lumens appears to take place as a result of one or more membrane-specific forces with a nonosmotic origin but this tendency to expansion can be overcome if the spectrin network on only one side of a contact zone is intact. PMID- 1760503 TI - Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance. AB - We have used pairs of electrically coupled cardiac cells to investigate the dependence of successful conduction of an action potential on three components of the conduction process: (a) the amount of depolarization required to be produced in the nonstimulated cell (the "sink" for current flow) to initiate an action potential in the nonstimulated cell, (b) the intercellular resistance as the path for intercellular current flow, and (c) the ability of the stimulated cell to maintain a high membrane potential to serve as the "source" of current during the conduction process. We present data from eight pairs of simultaneously recorded rabbit ventricular cells, with the two cells of each pair physically separated from each other. We used an electronic circuit to pass currents into and out of each cell such that these currents produced the effects of any desired level of intercellular resistance. The cells of equal size (as assessed by their current threshold and their input resistance for small depolarizations) show bidirectional failure of conduction at very high values of intercellular resistance which then converts to successful bidirectional conduction at lower values of intercellular resistance. For cell pairs with asymmetrical cell sizes, there is a large range of values of intercellular resistance over which unidirectional block occurs with conduction successful from the larger cell to the smaller cell but with conduction block from the smaller cell to the larger cell. We then further show that one important component which limits the conduction process is the large early repolarization which occurs in the stimulated cell during the process of conduction, a process that we term "source loading." PMID- 1760504 TI - Raman microspectroscopic approach to the study of human granulocytes. AB - A sensitive confocal Raman microspectrometer was employed to record spectra of nuclei and cytoplasmic regions of single living human granulocytes. Conditions were used that ensured cell viability and reproducibility of the spectra. Identical spectra were obtained from the nuclei of neutrophilic, eosinophilic, and basophilic granulocytes, which yield information about DNA and protein secondary structure and DNA-protein ratio. The cytoplasmic Raman spectra of the three cell types are very different. This was found to be mainly due to the abundant presence of peroxidases in the cytoplasmic granules of neutrophilic granulocytes (myeloperoxidase) and eosinophilic granulocytes (eosinophil peroxidase). Strong signal contributions of the active site heme group(s) of these enzymes were found. This paper illustrates the potentials and limitations for Raman spectroscopic analysis of cellular constituents and processes. PMID- 1760505 TI - Gating current "fractionation" in crayfish giant axons. AB - Effects of changes in initial conditions on the magnitude and kinetics of gating current and sodium current were studied in voltage-clamped, internally-perfused, crayfish giant axons. We examined the effects of changes in holding potential, inactivating prepulses, and recovery from inactivation in axons with intact fast inactivation. We also studied the effects of brief interpulse intervals in axons pretreated with chloramine-T for removal of fast inactivation. We find marked effects of gating current kinetics induced by both prepulse inactivation and brief interpulse intervals. The apparent changes in gating current relaxation rates cannot be explained simply by changes in gating charge magnitude (charge immobilization) combined with "Cole-Moore-type" time shifts. Rather they appear to indicate selective suppression of kinetically-identifiable components within the control gating currents. Our results provide additional support for a model involving parallel, nonidentical, gating particles. PMID- 1760506 TI - ATP dependence of KATP channel kinetics in isolated membrane patches from rat ventricle. AB - The dependence of KATP channel activity on [ATP] has been examined in isolated membrane patches from rat ventricular myocytes. The steady-state [ATP] dependence of channel open probability could be described by a sigmoidal relationship with the ki ([ATP] causing half-maximal inhibition of open probability) = 25 microM and Hill coefficient of 2. Description of channel open- and closed-time distributions required at least 2, and 3, time constants, respectively. Long open channel lifetimes decreased with [ATP]; unconditional mean channel closed-times increased with [ATP]. Step decrease (jump) in bathing [ATP] resulted in a delay (of up to hundreds of milliseconds) followed by a pseudo-exponential rise of current (with a time constant of up to hundreds of milliseconds). The time course of channel current after changes of [ATP] (or the ATP-analogue AMP-PNP) was shown to be predominantly determined by the time course of diffusion into the tip of the electrode and to the membrane. This time course of diffusion of ATP into the pipette tip had to be taken into account when analyzing the current response to [ATP] steps. Several possible kinetic models of the ATP-dependent regulation of channel activity were considered. Adequate explanation of the data required a model with sequential ATP-binding sites. The model can account for the time course of channel opening after steps of [ATP], as well as for the steady-state dependence of P0 on [ATP]. The model predicts [ATP]-dependent closed and open lifetimes as were observed experimentally. PMID- 1760507 TI - pH-dependent structural transitions of Alzheimer amyloid peptides. AB - To understand the molecular interactions leading to the assembly of beta/44 protein into the hallmark fibrils of Alzheimer's disease (AD), we have examined the ability of synthetic peptides that correspond to the beta/A4 extracellular sequence to form fibrils over the range of pH 3-10. Peptides included the sequences 1-28, 19-28, 17-28, 15-28, 13-28, 11-28, and 9-28 of beta/A4. The model fibrils were compared with isolated amyloid with respect to morphology, conformation, tinctorial properties, and stability under denaturing conditions. Electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, and x-ray diffraction revealed that the ionization states of the amino acid sidechains appeared to be a crucial feature in fibril formation. This was reflected by the ability of several peptides to undergo fibril assembly and disassembly as a function of pH. Comparisons between different beta/A4 sequences demonstrated that the fibrillar structure representative of AD amyloid was dependent upon electrostatic interactions, likely involving His-13 and Asp-23, and hydrophobic interactions between uncharged sidechains contained within residues 17-21. The results also indicated an exclusively beta-sheet conformation for the synthetic (and possibly AD fibrils) in contrast to certain other (e.g., systemic) amyloids. PMID- 1760508 TI - The molecular origin of birefringence in skeletal muscle. Contribution of myosin subfragment S-1. AB - The state of optical polarization of He-Ne laser light diffracted by single skinned frog skeletal muscle fibers has been determined after decoration of the thin filaments of rigor fibers with exogenous S-1. Light on the first diffraction order was analyzed using optical ellipsometry for changes occurring in total birefringence (delta nT) and total differential field ratio (rT) and the experimental results compared with theoretical predictions. Fibers were examined with SDS-gel electrophoresis and electron microscopy as independent assays of S-1 binding. The binding of S-1 to the thin filaments caused a significant increase in rT and a small but significant decrease in delta nT. Release of bound exogenous S-1 with magnesium pyrophosphate demonstrated that the effect of S-1 on the optical parameters was reversible and both electrophoresis and electron microscopy demonstrated the presence of S-1 specifically bound to the thin filaments. Model simulations based on the theory of Yeh, Y., and R. Baskin (1988. Biophys. J. 54:205-218) showed that the values of delta nT and rT were sensitive to the axial bonding angle of exogenous S-1 as well as to the volume fraction of added S-1. Analysis of the data in light of the model showed that an average axial S-1 binding angle of 68 degrees +/- 7 degrees best fit the data. PMID- 1760509 TI - Flow rate measurements in isolated perfused kidney tubules by fluorescence photobleaching recovery. AB - We have developed a new application of the fluorescence photobleaching recovery (FPR) technique for instantaneous measurement of volume flow rates at any axial position along isolated perfused kidney tubules. The method requires fast data acquisition of emitted fluorescence through a photomultiplier (time resolution, 0.5 ms) coupled with differential interference contrast microscopy to measure luminal diameters accurately. While the tubule is perfused in vitro with an impermeant fluorophore (fluorescein sulfonate), a 20-ms bleach pulse reduces the fluorescence in the observation region by 20-25%. Fluorescence recovery is a direct function of perfusate velocity; diffusion plays no significant role in the early phase of recovery. A fluid dynamics approach to data analysis shows that fractional recovery increases linearly with time until t = L/2vm, where L is the length of the observation window and vm is the mean axial velocity. Practically, a linear regression analysis of the early recovery phase allows measurement of vm of up to 0.14 cm/s, i.e., a 40-nl/min flow rate in a 25-microns-diameter tubule. Calibration experiments in small glass tubes perfused at predetermined flow rates demonstrated good accuracy (within 10%) and reproducibility (coefficient of variation, 8.7%). In rat inner medullary collecting ducts microperfused at 4-40 nl/min, the correlation with a standard fluid collection method was excellent (r2 greater than 0.97). The method should also be suitable for the direct measurement of fluid flow rate in kidney tubules or blood vessels microperfused in vivo. PMID- 1760510 TI - Temperature dependence of drug blockade of a calcium-dependent potassium channel in cultured hippocampal neurons. AB - The temperature dependence of drug blockade of a calcium-dependent potassium channel K(Ca) has been studied in cultured CA1 hippocampal neurons. Channel openings from a 70-pS K+ channel were recorded when inside-out patches were exposed to a bath solution containing 140 mM K+ and 0.2 mM Ca2+. The mean open times of channel events were not significantly altered when the bath temperature was lowered from 24 degrees to 14 degrees C (Q10 = 1.2). Introduction of the drug RP-62719 into the bath solution (at 5 microM) resulted in the mean open time of the K(Ca) channel to be diminished by 85% (at 24 degrees C) with no change in the amplitudes of the unitary currents. Over the same temperature range of 24 degrees to 14 degrees C, in the presence of RP-62719, the mean open times were significantly prolonged (Q10 = 2.2). A simple open channel block scheme was used to determine the temperature dependence of the onward- (blocking) and off- (unblocking) rate constants. Thermodynamic analysis, using transition rate theory, showed that the blocking rate constant was associated with a large increase in entropy. The relatively high temperature dependence for channel blockade is not consistent with a rate-limiting process established by simple diffusion of the agent to a channel blocking site. Channel block may involve conformational changes in the channel protein as a consequence of hydrophobic interactions between drug and channel sites. PMID- 1760511 TI - Politics of pacemaker dominance. PMID- 1760512 TI - 1/f alpha power spectrum of the QRS complex does not imply fractal activation of the ventricles. PMID- 1760513 TI - Oxidative damage to the myocardium: a fundamental mechanism of myocardial injury. AB - Certain pathophysiologic conditions are able to shift normal oxygen metabolism towards univalent reduction, resulting in the production of reduced oxygen intermediates, including free radicals and their metabolites. Oxygen free radicals have been implicated in a number of pathologic conditions, including myocardial injury. The possible sources of oxygen free radicals, the detection of the radicals during ischemia/reperfusion and possible mechanisms of free radical damage are discussed. The clinical implications of free radical damage and the experimental drug therapies at present under investigation are also reviewed. PMID- 1760514 TI - Heart rate and cardiac energetics. AB - The heart and arterial system are matched in the sense that the heart pumps at maximal external power. Why external power is optimized and what regulatory mechanisms are responsible for this optimization are not known. In the present report we will suggest a mechanism of matching on the basis of the following arguments. 1) Mean aortic pressure, the perfusion pressure for most organs, most notably the cerebral circulation, is similar in mammals. 2) Heart period (T), a cardiac parameter, is related to body mass in a similar way as the decay time (tau = RpC, where R is peripheral resistance and C is total arterial compliance) of aortic pressure in diastole, a vascular parameter. In other words, the ratio of T/tau is similar in all mammals and assures a similar aortic pressure in diastole so that coronary perfusion, which mainly takes place in diastole, is guaranteed. 3) Assuming given mechanical properties of mammalian cardiac muscle, optimal power delivery relates to a minimal cardiac size; in other words, during evolution total cardiac volume was minimized, resulting in a heart that pumps at maximal power. PMID- 1760515 TI - The extracellular matrix in human myocardium: Part I: Collagens I, III, IV, and VI. AB - The composition of the extracellular matrix in normal human myocardium obtained at open-heart surgery was investigated using monoclonal antibodies against the collagens I, III, IV, and VI, and fluorescence microscopy. The aim of the study was to provide information on normal myocardium that could be used in the evaluation of pathological changes. Porcine myocardium was used for comparison, and both tissues showed a perfect agreement of the results, apart from collagen IV. This was negative in pig myocardium, due to the species specificity of the antibody. Collagens I and III were localized in the extracellular space as either coarse or fine fibrillar structures; the cellular elements of the interstitium, except for the endothelial cells, were also stained. Labeling for collagen VI was much finer than for the other collagens, and was present throughout the interstitium. Collagen IV stained the basement membranes of myocytes and capillary endothelial cells, and also labeled the T-tubular system in the myocytes. The second part of this communication will describe the localization of fibronectin, laminin and vimentin in normal human myocardium. PMID- 1760516 TI - Effects of propionyl-L-carnitine in chronically hypoperfused ("hibernating") myocardium. AB - The purpose of this report was to test the effects of systemic treatment with propionyl-L-carnitine in a new model of chronically hypoperfused ("hibernating") myocardium. Adolescent swine were instrumented to undergo a period of mild partial coronary constriction for 1 week (50% reduction of the maximum phasic flow velocity in the anterior descending coronary artery). This reduced regional mechanical function by 56%. The system satisfied criteria defining "hibernating" myocardium, in that the chronic hypoperfusion did not produce massive tissue necrosis and that the reduction in regional contraction remained responsive to inotropic stimulation. Treatment with 50 mg/kg propionyl-L-carnitine by mouth twice daily for 1 week significantly (p less than 0.0005) increased concentrations of free and total carnitine in the myocardial tissue by 39% and 31%, respectively. Treatment with propionyl-L-carnitine did not alter regional systolic shortening in either hibernation or reperfusion for 2 hours, but enhanced one estimate of contractility reserve based on the rate of left ventricular emptying with occlusion of the inferior vena cava. Propionyl-L carnitine did not reverse the observed impairments in mitochondrial respiration (diminutions in state 3 respiration and the respiratory control ratio), but limited the number of lesions seen on histological examination. Six out of eight placebo hearts showed one or more changes of ischemia, infarction or reperfusion injury, while the same was true in only two out of eight hearts treated with propionyl-L-carnitine (p less than 0.003). Carnitine and various analogues have been proposed to benefit ischemic myocardium. The present data suggest that this general sparing effect may also occur with the propionyl derivative in chronically underperfused myocardium. PMID- 1760517 TI - The efferent mechanisms of reflex hemodynamic responses to distension of the descending colon in anesthetized dogs. AB - We have recently shown that distension of the descending colon in anesthetized dogs causes reflex increases in heart rate, aortic blood pressure and the maximal rate of rise of left ventricular pressure, involving afferent pathways in the hypogastric nerves. In this study we have examined the efferent mechanisms involved in those responses. The descending colon was distended using Ringer solution at constant pressure in 13 anesthetized dogs. As previously shown, distension of the colon caused an increase in aortic blood pressure, heart rate and the maximal rate of rise of left ventricular pressure. The increase in the aortic blood pressure was abolished by either bretylium tosylate or phentolamine. Propranolol or bretylium tosylate abolished the increases in heart rate when changes in the aortic blood pressure were prevented, and abolished the increases in the maximal rate of rise of left ventricular pressure when the increases in heart rate were also prevented. These results indicate that the reflex increases in heart rate, arterial blood pressure and the maximal rate of rise of left ventricular pressure involved efferent sympathetic pathways. PMID- 1760518 TI - Diuretics as initial and sole treatment in chronic cardiac failure. AB - Six patients with chronic congestive cardiac failure, who had never received any drug treatment, were studied before and after one month of therapy with frusemide alone at a dose of 40 mg a day. Measurements were made at rest of plasma epinephrine, norepinephrine, renin activity, aldosterone, atrial natriuretic peptide, cortisol, growth hormone and prolactin, together with central hemodynamics, body fluid volumes and renal function. The initial measurements of hemodynamics, body fluid compartments and renal function confirmed the presence of the physiopathology typical of congestive cardiac failure. Plasma concentrations of norepinephrine, atrial natriuretic peptide, aldosterone and growth hormone were significantly increased. The mean value of plasma renin activity, although high, was not significantly different from normal. After one month of treatment, body weight, body fluid volumes and exchangeable sodium were reduced. Hemodynamics and renal plasma flow and glomerular filtration were not significantly affected. Plasma norepinephrine fell to within normal limits; atrial natriuretic peptide increased significantly; plasma renin activity and cortisol increased to levels which were abnormally high; growth hormone increased to levels similar to those associated with acromegaly. Increased circulating concentrations of atrial natriuretic peptide during treatment by frusemide may have an important influence on the kidney, blood vessels and neuro-endocrine response. PMID- 1760519 TI - Platelet-mediated cytotoxicity and its enhancement by platelet activating factor. AB - Platelet cytotoxicity was assessed in 70 cancer patients with various tumor localizations and in 30 normal donors. The data presented reveal that the ACL cell line displays the highest sensitivity to platelet cytotoxicity. Using the ACL cells, we discovered that platelets from oncological patients and normal donors display comparable cytotoxicity. The level of platelet lytic activity is irrelevant to tumor localisation; however, it appears to be dependent on the stage of tumor growth. Incubation of platelets, both from donors and patients, with PAF (concentration range 10 pM to 10 nM) results in a significant rise of the killing activity of platelets. PAF induces greater cytotoxicity enhancement for platelets with lower initial activity, this pattern appearing to be the specific feature of the PAF mediated effect. Hence, platelets can be considered as effector cells relevant to antitumor immunity; PAF-mediated enhancement of platelet cytotoxicity can appear to be useful in the search for new immunotherapeutic drugs. PMID- 1760520 TI - Monocytic origin of fibroblasts: spontaneous transformation of blood monocytes into neo-fibroblastic structures in osteomyelosclerosis and Engelmann's disease. AB - We describe here two pathological situations, osteomyelosclerosis and Engelmann's disease, in which HLA-DR blood monocytes modulate to the fibroblastic class, in long-term culture. Monocytes/macrophages were identified by immunofluorescence, using monoclonal antibodies against surface markers (Leu M3, CD 68, and HLA-DR) and the neo-fibroblasts by electron microscopy and immunofluorescence using monoclonal antibodies against a cytoplasmic enzyme specifically involved in the synthesis of collagen (5B5). Macrophages makers were found on the neo fibroblasts, whereas HLA-DR macrophages expressed the cytoplasmic marker 5B5. Since osteoblasts are classically derived from fibroblasts, the significance of the in vitro differentiation of monocytes/macrophages into fibroblasts to the in vivo mechanism leading to excessive osteoblastic proliferation in both osteomyelosclerosis and Engelmann's disease, is discussed. The possible involvement of this pathway leading from monocytes to fibroblasts and osteoblasts in the normal process of bone modeling and remodeling in questioned. PMID- 1760521 TI - Effect of fusafungine on adherence of Haemophilus influenzae type b to human epithelial cells in vitro. AB - Haemophilus influenzae, a normal host of the nasopharynx of humans, may become a pathogen. The first step of infection is adherence to epithelial cells of the nasopharynx through glycopeptidic adhesins, or pili. Adherence to human epithelial cells in continuous lines, HeLa and Hep2, of 8 piliated strains of Haemophilus influenzae isolated from human infections of the respiratory tract was studied in vitro in the presence of fusafungine, a local bacteriostatic antibiotic. When the bacteria were grown in the presence of 0.5 x the MIC, fusafungine afforded 45-75% of adherence inhibition, but this inhibitory effect did not parallel the MICs. In contrast, no significant effect could be observed either when epithelial cells were exposed to 0.5 x the MIC before use in the adherence assay, or when this assay was performed in the presence of 0.5 x the MIC of fusafungine. The partial adherence inhibition observed suggests that fusafungine interacts with the bacterial binding sites but that other mechanisms may contribute to the inhibitory process. This effect of fusafungine should prevent but not eradicate colonization of the nasopharyngeal mucosa by Haemophilus influenzae and may account for the therapeutic efficacy reported in infections of the respiratory tract due to Haemophilus influenzae. PMID- 1760522 TI - Calcitonin and metabolic alkalosis. AB - Calcitonin is used in the treatment of osteoporosis and several adverse effects, such as rash, antibody presence, hypocalcemia, etc have been reported with the therapeutic use of large quantities of this hormone. The results found in this paper show that 7 h after administration of large doses of calcitonin to osteoporotic patients on hormone treatment, the acid-base status shifts to metabolic alkalosis. This represents another adverse effect of the use of pharmacological doses of calcitonin. PMID- 1760523 TI - Increased level of soluble interleukin-2 receptor in sera of patients with Graves' disease. AB - Soluble interleukin-2 receptor was studied in 20 patients with Graves' disease before and after methimazole treatment. Soluble interleukin-2 receptor level was significantly increased in newly diagnosed Graves' disease compared to controls (667 +/- 270 vs 205 +/- 45 U/ml) (P less than 0.001). In untreated patients' sera the soluble interleukin-2 receptor levels were higher in patients with active ophthalmopathy than in those without eye symptoms. Soluble interleukin-2 receptor levels were normalized in remission induced by methimazole treatment in the majority of patients except those with infiltrative ophthalmopathy. Furthermore, a correlation was found at the hyperthyroid stage of the disease between soluble interleukin-2 receptor level and titre of anti-TSH-receptor antibodies. However, the association with other parameters including anti-eye muscle, anti-thyroid peroxidase, anti-thyroglobulin antibodies was not significant. PMID- 1760524 TI - Hypocalcemia and hypomagnesemia in cancer patients. AB - The aim of this study was to evaluate the incidence of hypocalcemia and hypomagnesemia and the relationship between calcium and magnesium serum levels in 82 hospitalized cancer patients, 61 of whom were in the terminal phase of the disease. The frequency of hypocalcemia and hypomagnesemia was 13.4% and 17.1% respectively. The incidence of hypocalcemia in patients with hypomagnesemia was 28.6%, while in those with normal or high magnesium serum levels it was 10.3%. The lowest magnesium serum level was observed in hypocalcemic patients. It may thus be concluded that hypocalcemia and hypomagnesemia are a frequent complication of malignant tumors mostly in the terminal stage of the disease, and that even hypomagnesemia could contribute to the development of tumor-associated hypocalcemia. PMID- 1760525 TI - Activated murine B cells promote CFU-S proliferation through the release of soluble factors. PMID- 1760526 TI - Detection of barbiturate-induced surface changes in cerebrocortical synaptosomes by phase partitioning in an aqueous two-phase system. AB - The barbiturates tested in this work (barbital, phenobarbital, thiopental and pentobarbital) modify the partition of synaptosomes in a Dextran T500 poly(ethylene glycol) 4000 two-phase system. Under adequate experimental conditions, the drugs increase the partition into the upper phase and this effect appears to be due to an action on the biological material and not on the interface potential of the system. This conclusion can be drawn from the fact that synaptosomes preincubated with low concentrations (0.1 mM) of barbital and pentobarbital maintained an increased partition into the upper phase. The extent of the effect observed appeared to be inversely proportional to the hydrophobicity of the drugs since phenobarbital and barbital showed a higher effect than thiopental and pentobarbital. Dithionite-induced anoxia, rotenone and ouabain also induced a similar increase of partition of synaptosomes into the upper phase, suggesting that the surface changes detected by phase partitioning modification of synaptosomes could be somehow related to the bioenergetic maintenance of the membrane ATPase. PMID- 1760527 TI - Up-modulation of phorbol dibutyrate receptors by carbachol and arachidonic acid in rat prostatic epithelial cells. AB - Phorbol dibutyrate (PDBu) binding to rat prostatic epithelial cells has been measured as an indirect determination of protein kinase C in this cell system. Analysis of [3H]PDBu binding using competitive displacement demonstrated a single class of PDBu receptors with a Kd = 141 nM and a binding capacity of 4.8 pmol PDBu bound/mg cell protein. Raising cytosolic Ca2+ levels by redistribution of intracellular Ca2+ after cell treatment with carbachol or arachidonic acid (which also affects the bulk biophysical properties of the cell membrane) resulted in up regulation of the available number of PDBu receptors. These results appear to be a consequence of PKC translocation from the cytosolic compartment to the plasma membrane after a cytosolic Ca2+ increase, confirming previous results in other cell systems. PMID- 1760528 TI - Increased insulin receptor binding in erythrocytes from growth hormone-deficient children. AB - Erythrocytes from growth hormone-deficient children (GHd-children) (n = 10) showed a statistically significant increase in insulin binding at low unlabeled insulin concentrations, together with a threefold decrease in apparent receptor affinity, as compared to control children (C) (n = 11). Scatchard analysis of the binding data using the two-site model revealed that both the receptor concentration R1 [GHd-children 0.10 +/- 0.01 ng/ml and C 0.03 +/- 0.002 ng/ml] and the dissociation constant KD1 [GHd-children (0.48 +/- 0.05) x 10(-9) M and C (0.19 +/- 0.01) x 10(-9) M] for high affinity-low capacity sites were significantly increased in erythrocytes from GHd-children, while neither receptor concentrations (R2) nor the dissociation constant (KD2) for low affinity-high capacity sites proved to be altered. These events were accompanied by a normal sensitivity to insulin as well as glucose tolerance in the GHd-group. The meaning of the increased insulin binding with normal insulin sensitivity in GH-deficiency is discussed. PMID- 1760529 TI - The influence of chlorpromazine on the potential-induced shape change of human erythrocyte. AB - The effect of chlorpromazine (CPZ) on the shape of human erythrocytes with different values of transmembrane potential (TMP) was investigated. The shape of red blood cells with negative values of the TMP remained unchanged after the formation of stomatocytes by chlorpromazine, while cells with positive TMP showed a characteristic time course of shape change during the incubation with CPZ. Experiments with vanadate show that this might be due to a difference in the activity of the phospholipid-translocase at different values of TMP. PMID- 1760530 TI - A significant pool of amino acids is adsorbed on blood cell membranes. AB - It is well known that the amino acids in the blood are distributed between the plasma and inside the cells. This study was conducted to determine whether amino acids can be located adsorbed on blood cell membranes. The amino acid concentration in the deproteinized haemolysed blood was higher than that in the fraction of blood after removal of the blood cell membranes by centrifugation. These results showed that a pool of amino acids representing 21.1% of the whole blood cell amino acids was adsorbed on the blood cell membranes of adult Wistar rats. The non-polar amino acids showed high adsorption on the membrane, whereas out of the polar amino acid group, only the non-ionic amino acids did adsorb. PMID- 1760531 TI - Dynamics of autocatalytic reaction networks. IV: Inhomogeneous replicator networks. AB - The inhomogeneous replicator equation is derived as the continuous time model for parallel first and second order autocatalytic replication of macromolecules in a flow reactor based on mass action kinetics. It is shown that the total concentration of replicating material determines the relative importance of the first order and the second order mechanism. A complete description of the dynamics of the first order model and some special features of the inhomogeneous replicator equation are presented. A minimal prebiotic scenario with the potentiality to develop cooperation is derived from the inhomogeneous replicator equation. In this model cooperation can emerge when the total concentration of replication material exceeds a certain threshold. Below this value, a single species is selected; which one is determined by the rate constants of the first order reaction alone. Above this threshold the second order process becomes important and may lead to cooperative behavior such as hypercycles. PMID- 1760532 TI - What is the role of predation on stability of natural communities? A theoretical investigation. AB - A basic question in ecology concerns the role of species interaction on dynamics of natural communities. In this framework, ecologists have considered predation, competition, mutualism, the three most important interactions, highlighting their specific effects on distribution and abundance of species, providing knowledge about phenomena like coexistence and extinction. This paper seeks to identify the effects of predation on stability of natural communities by mathematical models. Simple multispecies community models, organized in trophic levels, are analyzed by means of a qualitative technique, loop analysis, combined with a computer calculation procedure. Results do not support the hypothesis of predation as a stabilizing factor. Rather, the outcomes of the analysis suggest that predation may or may not stabilize a community. This depends on the predator's behaviour and on the network of the community. PMID- 1760533 TI - Modeling of biological and medical systems: a systemic strategy. AB - A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system. PMID- 1760534 TI - A theoretical analysis of the effect of placental metabolism on fetal oxygenation under conditions of limited oxygen availability. AB - The purpose of this theoretical paper is to examine the effects of placental metabolism on fetal oxygenation under conditions of limited oxygen availability. Features of the mathematical model used here include: (1) ordinary non-linear differential equations defining the oxygen partial pressure profiles in the maternal and fetal streams for a concurrent flow pattern; (2) the presence of maternal and fetal blood flow shunts; (3) consumption of oxygen by a metabolically active placenta; and (4) modification of the fetal input to the placenta by changing the rate of fetal oxygen consumption in response to changes in the rate of oxygen delivered to the fetus via the umbilical vein. Model parameters were chosen to be well within the range of values cited in the literature. Based on these calculations, we conclude that: (1) under normal conditions, approximately one-half of the fetal uterine-umbilical venous oxygen partial pressure difference can be attributed to placental oxygen consumption; (2) utilization of fetal oxygen to help maintain the metabolic activities of the placenta does not significantly impair fetal oxygenation under normal conditions; (3) consumption of oxygen by the placenta will have a significant detrimental effect on the rate of oxygen delivered to the fetus if oxygen availability is compromised; and (4) for the same rate of maternal oxygen delivered to the placenta, maternal hypoxemia has a significantly greater adverse effect on fetal oxygenation than does maternal anemia. PMID- 1760535 TI - Acute renal tubular and hemodynamic effects of the calcium antagonist felodipine in healthy volunteers. AB - To evaluate the renal tubular effects of felodipine in a low (1.25-mg) and a high (10-mg) dose, lithium clearance was measured and related to renal hemodynamics in 10 healthy volunteers. After felodipine (1.25 mg), mean blood pressure decreased 4 mm Hg and heart rate increased 4 beats per minute. GFR and renal hemodynamics were unaltered. Natriuresis and diuresis increased and lithium clearance and fractional excretion of lithium were unchanged as compared with placebo. Felodipine (10 mg) decreased mean blood pressure 8 mm Hg; heart rate increased 16 beats per minute, and plasma catecholamines were elevated. GFR was unaltered, whereas RBF increased and renal vascular resistance decreased. Natriuresis and diuresis were further increased, and lithium clearance and fractional excretion of lithium were elevated. In conclusion, felodipine in a low dose of 1.25 mg, which did not change renal hemodynamics, had natriuretic and diuretic effects at a predominantly postproximal tubular site, whereas a high dose of 10 mg, which increased RBF and decreased renal vascular resistance, had additional natriuretic and diuretic effects in the proximal tubule. PMID- 1760536 TI - Lack of plasma interleukin-1 beta or tumor necrosis factor-alpha elevation during unfavorable hemodialysis conditions. AB - Plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were determined by ELISA in 17 healthy controls, 23 HD patients, 10 continuous ambulatory peritoneal dialysis patients, and 15 chronic renal failure patients, as well as in 2 HD patients experiencing pyrogenic reactions. Another group of 10 chronic HD patients were dialyzed for 2.5 h, 5 with first-use Cuprophan membranes and 5 with first-use high-flux cellulose triacetate membranes. The mean bacterial and endotoxin concentrations of the dialysate used for HD treatments during the study period were 18,440 +/- 530 CFU/mL (mean +/- SEM) and 976 +/- 205 pg/mL, respectively. Blood specimens were obtained intradialysis and postdialysis for cytokine assay and were incubated to augment cytokine production. There was no difference in plasma IL-1 beta or TNF-alpha concentrations among the healthy controls, continuous ambulatory peritoneal dialysis patients, chronic renal failure patients, or HD patients. Neither cytokine increased significantly during or after HD. Two patients experiencing pyrogenic reactions had plasma TNF-alpha concentrations of 537 and 413 pg/mL, compared with matched controls of 6 and 0 pg/mL. Il-1 beta concentration did not differ from controls. We conclude that: (1) plasma IL-1 beta and TNF-alpha are not chronically elevated in chronic renal failure, continuous ambulatory peritoneal dialysis, or HD patients; (2) HD with new Cuprophan or cellulose triacetate membranes and high concentrations of dialysate endotoxin and bacteria does not cause elevation of circulating IL-1 beta or TNF-alpha; and (3) pyrogenic reactions might be mediated by TNF-alpha. PMID- 1760537 TI - The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients. AB - Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium. PMID- 1760538 TI - Regulation of taurine transporter activity in LLC-PK1 cells: role of protein synthesis and protein kinase C activation. AB - Taurine transporter activity increases after exposure of cultured renal epithelial cells to taurine-free medium for 24 h and decreases after incubation in high (500 microM) taurine. This adaptive response mimics that observed in rat kidney after manipulation of dietary taurine. In order to elucidate potential mechanisms involved in the regulation of beta-amino acid transporter activity, the role of RNA transcription, protein synthesis, and protein import (trafficking), as well as protein kinase C activation, on the control of taurine transport was examined in the continuous proximally derived LLC-PK1 renal cell line. Inhibition of RNA transcription with actinomycin D did not alter the up regulatory and down-regulatory adaptive responses. Inhibition of protein synthesis with cycloheximide prevented the increased taurine transport in response to taurine-free medium as well as the decrease in taurine transport after exposure to high taurine. Colchicine prevented the response to taurine-free medium but had no effect on the response to high-taurine medium. Exposure of confluent cell monolayers to the active phorbol esters, phorbol 12-myristate 13 acetate and phorbol 12,13 dibutyrate, resulted in a reduction in taurine uptake. The effect was seen within minutes of exposure but was not observed in the presence of the inactive phorbol 4-alpha. This inhibitory action was blocked by staurosporin, an inhibitor of protein kinase C (PKC). Treatment of cells with the diacylglycerol kinase inhibitor R59022, which results in increased intracellular diacylglycerol, a natural stimulant of PKC, also inhibited taurine uptake, providing further evidence for a specific effect of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760539 TI - Cellular electrolyte and volume changes induced by acidosis in the rabbit proximal straight tubule. AB - Cellular acidosis induced either by high Pco2 or by low HCO3- concentrations has been shown to cause cell swelling in isolated, lumen-collapsed, S2 segments of the rabbit proximal tubule (Sullivan et al., Am J Physiol 1990; 258: F831-F839). The swelling is not followed by a volume regulatory response. The ionic basis of the swelling has been investigated by measurement of the cellular K+, Na+, and Cl content (electron probe) and HCO3- concentration (pH-sensitive fluorescent dye). Cell content of K+, Na+, and Cl- was expressed as a ratio to P content. Exposure to 15% CO2 increased K/P from 0.98 to 1.16, Cl/P from 0.14 to 0.20, and Na/P from 0.09 to 0.11. Cell (HCO3-) increased from 22 to 32 mM. Reduction in bath (HCO3-) from 25 to 5 mM reduced cell (HCO3-) from 24 to 8 mM and increased K/P from 0.75 to 0.90. Na/P fell from 0.13 to 0.09, and Cl/P fell from 0.15 to 0.12. Thus, swelling resulting from acidosis induced by high CO2 was accompanied by an accumulation of K+, Cl-, and HCO3-; that resulting from acidosis induced by a fall in (HCO3-) was combined with an accumulation of K+ and an unidentified anion. To determine if the swelling induced by a fall in pH might be coupled with depolarization of the basolateral membrane, the effect of 1 mM barium was tested. Barium caused cell volume to increase 10.2%. Cell pH rose from 7.38 to 7.56, K/P increased from 0.63 to 0.73, Na/P did not change, and Cl/P rose from 0.17 to 0.20. Cell (HCO3-) increased 10.4 mM. When the pH of the barium-treated tissue was reduced to 7.02 by raising Pco2, additional cell swelling and accumulation of K+ occurred. The effect on cell volume of a reduction of bath (HCO3-) from 25 to 5 mM at constant bath pH was determined. Cell pH was not altered. Cell volume decreased 3% initially and then returned to the control level. When the bath (HCO3-) was restored to 25 mM, cell volume increased 3.9% and then returned to the baseline. Thus, volume regulation was not impaired. It was concluded that a fall in cell pH induces swelling, and this is coupled with an accumulation of K+. This is probably the result of a pH effect on barium-sensitive and barium insensitive K+ conductance pathways. The nature of the anions that balance the gain in K+ depends on the means used to induce acidosis. PMID- 1760540 TI - Minimizing hemorrhagic complications in dialysis patients. AB - Renal failure is associated with an increased incidence of hemorrhage from a variety of sites, particularly in patients undergoing surgical procedures. The primary factors in the pathogenesis of bleeding in renal failure are platelet biochemical abnormalities and alterations in platelet vessel wall interactions. Hemodialysis improves hemostatic abnormalities in uremia, but the need for heparinization during the procedure may increase the bleeding risk. The risk of bleeding may be minimized by using peritoneal dialysis or alternative means to routine heparinization to prevent clotting in the extracorporeal circulation during hemodialysis. These include use of minimal heparin, prostacyclin, regional citrate anticoagulation, and no anticoagulation. Continuous arteriovenous hemodialysis may also be performed with regional citrate anticoagulation. There are several nondialytic therapies that may be used to prevent or treat hemorrhage in renal failure patients. These include administration of cryoprecipitate, 1 deamino-8-arginine vasopressin, estrogens, red blood cells, and erythropoietin. A clinical strategy to minimize bleeding complications in dialysis patients is presented. PMID- 1760541 TI - Verapamil improves the outcome after cadaver renal transplantation. AB - Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760542 TI - Influence of adenosine receptor blockade on renal function and renal autoregulation. AB - Experiments were conducted in anesthetized dogs to evaluate the effects of adenosine receptor blockade on renal function and on autoregulation of total RBF and outer cortical blood flow. After control measurements, the adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX) was infused intrarenally for 45 min at 2 or 6 microM/min. Responses to PSPX were compared with those obtained during infusions of either aminophylline or theophylline. PSPX infusion led to substantial increases in urine flow and sodium excretion (four- to fivefold). RBF increased significantly; however, outer cortical blood flow and GFR were not significantly altered. PRA increased twofold during PSPX infusion. The vasoconstrictor responses to bolus injections of 2-chloroadenosine (100 mumol) were attenuated by 58 and 86% during the low and high doses of PSPX and to a lesser extent with aminophylline/theophylline infusions. At renal arterial pressures above the inflection point, the slope of the average pressure-flow relationship during PSPX infusion was close to zero and was not significantly different from control. Similarly, autoregulatory capability was not altered during infusions of theophylline or aminophylline. These data provide further evidence that endogenous adenosine contributes substantially to the control of renin release but only modestly to the control of RBF and GFR and to renal autoregulatory capability. The natriuretic responses during adenosine blockade, which occurred in the face of elevated renin levels, support the hypothesis that endogenous adenosine enhances tubular sodium reabsorption rate. PMID- 1760543 TI - Implementing a computerized operating room management system. AB - The Queen's Medical Center implemented a computerized operating room management system in 1987 that includes surgery scheduling, intraoperative recording, and resource tracking. In addition to the important functional components, the system provides management with a better tool for decision-making. The purpose of this article is to describe this implementation. Background is provided to identify the manual system's deficiencies followed by the anticipated benefits of the computer system. The paper concentrates on Queen's implementation experiences in coding the surgical procedure information, confronting staff anxiety, managing the changing roles of the staff and providing adequate resources. Minimum requirements for a successful implementation include designating an effective project leader, assigning system responsibilities to the user, relieving all operational responsibilities from key members of the project team and providing adequate resources to support the system. PMID- 1760544 TI - Resource scheduling: from theory to practice. PMID- 1760545 TI - Knowledge-based schedule formulation and maintenance under uncertainty. AB - This paper is concerned with the dual sequential problems of (1) determining an acceptable personnel schedule over a specified time period, and (2) adjusting that schedule during the course of its execution in reaction to daily changes in both demand and available personnel. The first problem is schedule formulation; the second sequential problem is schedule execution. A rule-based, hierarchical system has been developed for first modeling and then solving both the schedule formulation and the schedule execution problems as a two-phase dependent process. The system is applied to the scheduling and staffing of nurses. A double-blind evaluation was conducted, which ascertained the quality of the resultant schedules in terms of maintainability, coverage, and personal satisfaction. The evaluation indicates that for units on which personnel changes have occurred, the prototype appears to perform as well as human schedulers. PMID- 1760546 TI - Automated nurse scheduling. AB - This article attempts (1) to define the several aspects of scheduling nursing personnel within the general context of nursing management, (2) to briefly review the history of the application of operations research and computers to scheduling nurses, (3) to describe what nursing administration is looking for in an automated scheduling system, (4) to review a typical system, and then (5) to discuss issues of implementation from the viewpoint of nursing administration, including realizable benefits. PMID- 1760547 TI - Continuous personnel scheduling algorithms: a literature review. AB - Hospitals frequently use personnel scheduling options as recruiting and retention instruments. The successful application of these personnel scheduling tools, whether developed in-house or purchased from vendors, requires appreciation of the interrelationships of three basic manpower decisions--staffing, personnel scheduling, and allocation. This article introduces these basic relationships and their influence on the development of satisfactory personnel schedules. Next, it reviews published personnel scheduling algorithms, applicable to hospital operations, within the context of the three manpower decisions. It is proposed that scheduling algorithms be classified by type of schedule produced (cyclic or noncyclic); and technique used (heuristic, mathematical programming, or self scheduling). The characteristics of each classification are discussed. Considerations for the development of new personnel scheduling algorithms are also presented. PMID- 1760548 TI - Computerized clinic scheduling system at the University of Michigan Medical Center. AB - The University of Michigan Medical Center has a flexible computerized clinic scheduling system that handles approximately 750,000 visits per year at the main hospital and satellite locations. The system includes a wide variety of fully integrated functions, including appointment booking, multiple and series scheduling, wait and reschedule lists, routine reminder notices, routine requests for medical records and radiology reports, no-show follow-up, and managerial reporting at multiple levels of detail. The system is extremely flexible, and allows separate scheduling specifications for every physician and all other resources within the system. The system is available at any of the approximately 1,800 computer terminals throughout the Medical Center, and is regularly used at approximately 400 terminals. PMID- 1760549 TI - Resource and appointment scheduling: closing the information loop. AB - Hospital-wide preparation is currently underway for a new patient care information system at Baystate Medical Center in Springfield, Massachusetts. Integral to this new system are two new products recently developed by the TDS Healthcare Systems Corporation: a permanent patient record system and a resource and appointment scheduling application. The new patient care information system can maintain up to 16 million records on-line and can be used throughout the medical center. This article will focus on the resource and appointment scheduling application and how it can be used to track resource utilization and close the information loop related to patient appointment activities. PMID- 1760550 TI - Gay men and HIV/AIDS: understanding the double stigma. AB - Many men with HIV/AIDS are and will continue to be homosexual or bisexual. Effective care requires understanding the impact of the double stigma of being gay and having HIV/AIDS. While providers have traditionally focused on gay men with HIV disease as individuals, this article directs providers' attention to the importance of social dimensions in creating a plan of care. PMID- 1760551 TI - Overcoming methodological barriers to HIV/AIDS nursing research. AB - While more than 1,600 articles have been published in the nursing literature about HIV infection, only 54 (3%) have been research articles. The sparsity of nursing research related to HIV has partially resulted from methodological problems inherent in the implementation of research protocols with persons infected with HIV. The authors' focus is on methodological and ethical problems related to sampling patterns, informed consent, and protection of human subjects that have hindered the study of HIV infection. The underlying reasons for these problems as well as solutions and approaches to minimize or prevent the problems are presented. PMID- 1760552 TI - How long can HIV survive on environmental surfaces? PMID- 1760553 TI - Association of Nurses in AIDS care. Position paper: duty to care. PMID- 1760554 TI - Ten years: looking back, looking forward. PMID- 1760555 TI - Tuberculosis: the other epidemic. AB - In 1990, the number of cases of tuberculosis (TB) reported in the United States rose 6%. This is a noticeable change since, in prior years, TB had been declining. The increased incidence of TB is largely related to the HIV epidemic. TB is of particular interest in HIV-related illnesses, since it is preventable and treatable. The presentation of HIV-associated TB is different from "standard TB." Nurses need to be informed about the clinical presentation of the disease, the procedures to diagnose it, the treatments, and their potential side effects. PMID- 1760556 TI - The effect of flow on the interaction of isolated megakaryocytes with subendothelial extracellular matrix. AB - We have previously shown that human, guinea pig, or rat megakaryocytes, incubated under static conditions on an extracellular matrix (ECM) produced by endothelial cells, readily adhered to the matrix and underwent platelet-like shape change and thromboxane A2 secretion. We have now exposed megakaryocytes to ECM in a perfusion system similar to that used to study platelets circulated over aortic subendothelium. We used a continuous flow circuit incorporating a parallel plate perfusion chamber. Megakaryocytes were isolated to high purity from guinea pig marrow by centrifugal elutriation and velocity sedimentation. The cells were introduced into the flowing medium while the surface of an ECM-coated coverslip mounted in the chamber was observed continuously by phase-contrast video microscopy for up to 18 hours. Megakaryocytes from the flowing suspension started to adhere to the ECM within seconds. Significant adhesion occurred over a range of shear rates, from 10 to 190 seconds-1, did not appear above 300 seconds-1 and was greatest at a shear rate of 60 seconds-1. Adhesion to the ECM was specific, since there was no adherence to glass coverslips, glutaraldehyde-fixed ECM-coated coverslips, or to endothelial cells cultured on ECM-coated coverslips. At low shear rates large aggregates of megakaryocytes formed on the ECM surface; these could be detached and washed away by higher shear forces. Megakaryocytes thus acquire, even before platelet formation, an adhesive capacity similar to that of platelets. In addition, a significant fraction of the adherent megakaryocytes underwent elongation and pseudopod formation similar to that seen in marrow sinusoids. PMID- 1760557 TI - The platelet open canalicular system: a final common pathway. AB - Channels of the surface-connected, open canalicular system (OCS) of human platelets serve as the pathway for transport of substances into the cells and as conduits for the discharge of alpha granule products secreted during the platelet release reaction. The purpose of the present study was to determine if both functions of the OCS can take place simultaneously. Suspensions of washed platelets were exposed to thrombin at 1 U/ml for 5, 60, or 180 seconds in the presence of fibrinogen molecules coupled to particles of colloidal gold (Fgn/Au). The samples were fixed in a low concentration of glutaraldehyde and embedded in L.R. White resin to preserve antigenicity. Thin sections were exposed to a rabbit polyclonal antibody to human fibrinogen followed by an anti-rabbit IgG coupled to 5-nm gold beads. Thrombin caused Fgn/Au particles to bind to platelets and enter channels of the surface-connected OCS. Endogenous fibrinogen detected by immunogold 5-nm beads were localized to alpha granules in resting platelets and 5 seconds after thrombin stimulation. At 60 seconds and 3 minutes Fgn/Au particles were present in swollen alpha granules, as well as OCS channels. Fibrinogen gold beads were evident in alpha granules and OCS channels connected to the platelet surface. The 18- to 20-nm Fgn/Au particles were in the same channels of the OCS as fibrinogen gold beads. The OCS is a final common pathway for uptake of particulates and discharge of secretory products in thrombin-activated human platelets. PMID- 1760558 TI - Accurate determination of mean cell volume by isotope dilution in erythrocyte populations with variable deformability. AB - Variations in erythrocyte deformability and morphology lead to artifacts in electronic determinations of mean cellular volume (MCV) by the aperture-impedance method. The micropipette-aspiration technique loses accuracy when applied to severely aberrant cells such as dense sickle cells. A new light-scattering technique requires that the cells be capable of undergoing isovolumetric sphering. In contrast, the isotope-dilution (ID) method measures absolute mean volume and is free of artifacts associated with abnormal deformability or morphology. It does not depend on any algorithms or correction factors and does not subject the cells to any stringent processing, not even centrifugation. The ID method can be used to determine the mean volume of red cells in hypo- or hypertonic media or in the presence of pharmacologic agents. It requires no more than a 1-ml aliquot of suspended cells at a hematocrit of at least 30%. The cells can be readily recovered, washed, and reused. Using EDTA labeled with 57Co as an extracellular space marker we have used ID to determine the MCV of fractionated normal human red blood cells (RBC), unfractionated RBC containing SS hemoglobin, and RBC from four other mammalian species. In the case of human RBC obtained from eight normal donors, we obtained mean MCV values (+/- SD) of 83.6 +/- 3.0, 87.5 +/- 3.9, and 76.5 +/- 5.3 fl for unfractionated and top and bottom 10% density fractions, respectively. The value 83.6 is significantly lower than the generally accepted range of 89-91 indicated by electronic analyzers calibrated against spun microhematocrits. The discrepancy of about 7% can account for the difference between mean cell hemoglobin concentration (MCHC) data determined by a calibrated Coulter Counter and corresponding data obtained with paired samples using a cyanmethemoglobin procedure specified in NCCLS Standard H15-A and corrected for trapped plasma. PMID- 1760559 TI - Effect of dehydration on the viscoelastic behavior of red cells. AB - Dehydration of red cells alters their rheological behavior and may contribute to the pathology of disorders such as sickle cell disease. We have measured the viscoelastic properties of individual human HbAA red cells after graded dehydration induced by incubation with valinomycin at different external K levels. With dehydration, the cells underwent progressive reduction in their rate of extensional shape recovery (i.e., after elongation by micropipette manipulation). Their rigidity remained unaffected until the mean cell hemoglobin concentration (MCHC) rose above 50 g/dl, but then increased about 100% as judged from the response of membrane tongues drawn into micropipettes. There was also a marked reduction in the shape recovery rate at this level of dehydration, and the cells no longer behaved elastically but rather showed unrecoverable residual deformation. Additionally, the cytoplasm took on solid-like properties. Changes in cell rigidity and shape recovery rate have been previously demonstrated for dense sickle cells; our results indicate that normal red cells can be induced to behave similarly, but that a greater degree of dehydration is required. PMID- 1760560 TI - Ultrastructural and morphometric alterations in bone marrow stromal tissue after 7 Gy irradiation. AB - To evaluate the response of marrow stroma to 7 Gy irradiation, femoral bone marrow was fixed by vascular perfusion (so as to avoid the artificial destruction of sinus endothelia), and was examined using light and electron microscopy with morphometric methods. The radiation caused a marked decrease in hematopoietic cell number (NHC) within 3 days post-irradiation, followed by total recovery of hematopoiesis, which occurred gradually over 28 days. An increased number of fat cells was seen by 7 days. During the whole course of hypoplasia and recovery, the continuity of sinus wall, three-dimensional reticular mesh work in hematopoietic parenchyma, gap junctions (GJ) between stromal cells, the adventitial cell cover of sinus wall (ACC), and the stromal cell numbers of reticular cells (RC), sinus endothelia (SE), and macrophages (MP) were maintained. The cellularity of stromal components of RC, SE, and MP seemed passively increased in contrast to a reduction in numbers of NHC. A similar tendency was observed (1) between NHC and ACC and (2) between GJ and the cellularity of fat cells, which had a statistical significant correlation (p less than 0.05; t-test). The mechanism of radio resistance in bone marrow stroma and the possible functional adaptation and cellular coordination after irradiation are discussed. PMID- 1760561 TI - Response of marrow stroma to ionizing radiation. PMID- 1760562 TI - Optimized recirculation survival of mouse carrier erythrocytes. AB - Carrier mouse erythrocytes prepared by a hypotonic dialysis technique and reinjected into mice have a 24 hour survival of approximately 50%. Twenty-four hour survival can be improved substantially to 74% by removing the more fragile erythrocytes by a hypotonic wash treatment. The mean cell volume of the carriers prepared by this modification is significantly (p less than 0.01) different from cells prepared by the standard method with a isotonic wash treatment. Carriers prepared by the hypotonic treatment wash modification exhibit a different 50% hemolytic value (15% difference) from isotonically prepared carriers, and normal erythrocytes. Carrier-erythrocytes removed from mice 24 hour post-injection exhibit an osmotic profile that is independent of the treatment. Carriers were also prepared by another modification of the encapsulation procedure and held in a permeable state overnight before resealing and annealing. Carriers prepared in this manner showed a much lower 24 hour survival (13%). PMID- 1760563 TI - Epidemiology of inflammatory bowel disease over a 10-year period in Florence (1978-1987). AB - The epidemiology of inflammatory bowel disease (IBD) in southern Europe is still not well-known. Sporadic reports have suggested a lower incidence and a milder course of the disease in Italy, but conclusive data are still lacking. To shed light on this issue, we conducted a retrospective study of IBD incidence (from January 1978 to December 1987) in the metropolitan area of Florence (650,000 inhabitants). We also estimated IBD prevalence at December 31, 1987. Our study included both in-patients and out-patients referred to the Gastroenterological and Surgical Departments of the area. The diagnosis was based on well-established clinical, endoscopical, radiological, histological and surgical criteria. Overall, nine-hundred IBD patients were identified, but only 359 (195 males, 164 females) met the eligibility criteria for inclusion in the incidence study (area of residence and period of diagnosis); of these, 263 had ulcerative colitis (UC), 96 had Crohn's disease (CD), and 6 had IBD. The average incidence rate of CD was 1.5/100,000 per year while its prevalence was 17.3/100,000. The average incidence rate of UC was 4.0/100,000 per year and the prevalence was 49.6/100,000. Both the incidence and the prevalence rates for UC and CD were higher in males than in females. This retrospective, hospital-based study shows that, in this area, the incidence rate of IBD has steadily increased over the period considered. Further studies specifically focused on risk factors are needed. PMID- 1760564 TI - Early endoscopic cholangiopancreatography and sphincterotomy in acute biliary pancreatitis: report of 50 cases. AB - Endoscopic retrograde cholangiopancreatography (ERCP) was successfully performed in 49/50 consecutive patients with acute pancreatitis and suspected biliary aetiology in the early phases of the disease (24-72 hours from admission). ERCP showed common bile duct lithiasis and/or stenosis (25 cholecystectomized patients) in 41/49 cases (83.7%). In 38 patients endoscopic sphincterotomy (ES) was performed: stone removal was possible in lithiasic patients (36 cases, 13 previously cholecystectomized); 3 further patients showed a main pancreatic duct stenosis (2 of these underwent pancreatic ES). The patients treated with ES showed a quick improvement in symptomatology and clinical outcome; no adverse effect of ERCP was found; no mortality was registered. Comparison with a previous series of 130 cases of acute biliary pancreatitis (ABP) showed a reduction in mortality, complications and length of hospitalization. These findings suggest that, from a diagnostic and therapeutic point of view, early ERCP is safe and useful in ABP. PMID- 1760565 TI - Fasting H2 breath values revised. PMID- 1760566 TI - Acute biliary pancreatitis. AB - Technological innovations in the past decade suggest that their systemic utilisation in acute biliary pancreatitis may have a significant impact on diagnosis and treatment. Urgent severity assessment resulting in the use of ERCP in patients with probable gallstones is essential since early endoscopic sphincterotomy may reduce morbidity and mortality. Contrast enhanced CT scanning is indispensable to the clinical decision-making process resulting in surgical intervention for necrosectomy. A rational application of diagnostic modalities, including ERCP, duodenal bile crystal analysis and dynamic biliary scanning, can greatly increase the proportion of patients with aetiological diagnosis, thereby enabling treatment to prevent further attacks. A fundamental knowledge of the patho-biochemical and patho-physiological nature of acute pancreatitis, however, is still required for further progress. PMID- 1760567 TI - The "stepchild" of gastroenterology? PMID- 1760568 TI - Omeprazole in short-term treatment of Helicobacter pylori positive duodenal ulcer. PMID- 1760569 TI - Evaluation of health and productivity of small ruminants in Africa: the example of Senegal. AB - The authors describe a system of investigation introduced into Senegal in 1983; their purpose is to extend knowledge about the farming of small ruminants and the epidemiological relevance of such farming. The investigations are conducted in the traditional livestock sector by using a multidisciplinary approach. The precision and reliability of the information depend on the recording and processing of data on individual animals. The system of investigation has a modular structure organised around a central module for demographic surveys. The peripheral modules correspond to specific activities: clinical surveillance, recording changes in body state, laboratory tests and a study of animal husbandry conditions and practices. The authors distinguish four levels of analysis depending on the origin of variables under consideration: a single module (level 1), the demographic module plus the peripheral module (level 2), the demographic module plus two or more peripheral modules (level 3) and one or more modules derived from experimental modification of certain features of the husbandry system (level 4). The constraints and limitations of the procedure are discussed. PMID- 1760570 TI - Information systems for animal health: objectives and components. AB - As in most other technical and management fields, information management is fast becoming the key to effective action in animal health. A modern veterinary service requires effective systems for gathering relevant information from the field, processing it in ways which provide maximum value, and presenting it in a form which is easy for national policy-makers and field staff to use in implementing appropriate actions to achieve effective disease control. This paper describes seven objectives which should form the basis for developing an integrated national animal health information system. It also specifies six criteria which any information-gathering activity should be required to meet before it is allowed to commence. For each of the seven objectives, a description is given of how the particular component of the system can be used, with examples of how such information management procedures have been implemented in practice. Attention is drawn to other papers in this issue which describe various innovative techniques currently used to meet some of the objectives of a modern animal health information system. PMID- 1760571 TI - Application of ecopathological methods to the investigation of health problems on farms. AB - Application of the techniques of ecopathology to the investigation of health problems on farms has allowed a specific methodology for the study of enzootic diseases of multiple aetiology, dominant under intensive husbandry, to be developed. New knowledge about such diseases has accumulated for various species of animals. Finally, a procedure for regulating and managing the health risks of livestock farming is proposed. PMID- 1760572 TI - Geographic information systems: their application in animal disease control. AB - Geographic information systems (GIS) are computerised information systems that allow for the capture, storage, manipulation, analysis, display and reporting of geographically referenced data. They have been used in recent years for a wide variety of purposes, including town planning and environmental resource management. The technology has many features which make it ideal for use in animal disease control, including the ability to store information relating to demographic and causal factors and disease incidence on a geographical background, and a variety of spatial analysis functions. A number of possible veterinary applications are suggested, and three examples of the use of GIS in New Zealand are discussed. PMID- 1760573 TI - Satellite imaging as a technique for obtaining disease-related data. AB - Because of its initial expense, remote sensing imagery has been frequently ignored in studying the epidemiology and ecology of human and animal diseases. However, these digital images have many advantages when the theoretical restrictions and constraints on the data are understood. Remote sensing imagery has the potential significantly to improve the effectiveness and delivery of disease control programmes. As soon as it can be integrated into the operational aspects of programmes, remote sensing imagery will pass from being a data-driven research tool to being need-driven. PMID- 1760574 TI - Epidemiological methods for investigating wild animal reservoirs of animal disease. AB - The epidemiological and ecological methodologies used to investigate tuberculosis in badgers (Meles meles) in Great Britain are reviewed. The objectives of these studies have been, on the one hand, to investigate the causal association between Mycobacterium bovis infection in badgers and the occurrence of tuberculosis in cattle and, on the other, to acquire knowledge of the population biology of badgers and the dynamics of infection in order to identify, formulate and assess potential strategies. The studies provide examples of the possible approaches and the practical difficulties that investigations of wild animal populations present; the importance of a multi-disciplinary team which can be maintained for the protracted periods necessary for prospective studies is also highlighted. The most successful components of the research programme have been specific prospective studies of populations, as they provide the only means of understanding the dynamic aspects of the population biology and the epidemiology of infection and disease. Expedient, cross-sectional studies have, however, proved valuable in supplementing the main long-term studies. PMID- 1760575 TI - The application of risk assessment methods in making veterinary public health and animal health decisions. AB - The newly emerging discipline of quantitative risk assessment has wide application in the field of veterinary public health and animal health. Regulatory authorities are increasingly faced with public policy decisions that must assess the risks of new technology or practices relative to the potential benefits, thereby establishing a level of acceptable risk. The elements of risk are a choice of action, a probability of loss and a magnitude of loss. Perceived risk and actual risk are seldom equivalent; adoption of the methodologies used in technological and human health risk assessments will allow veterinary regulators to make better decisions. Determination of levels of acceptable risk are increasingly dependent on quantitative models, and examples are presented for evaluation of different post-mortem meat inspection systems, estimating disease risks associated with animal embryo transfer and formulating national border protection strategies. All models have some degree of subjectivity, and the decisions made by regulators and risk managers should incorporate a wide knowledge of the risk assessment process, as well as the conditions of use that will occur in the real world. PMID- 1760576 TI - Steps in the implementation of a micro-computer approach to the management of animal disease information. AB - The stages in the design, procurement and implementation of a micro-computer based animal health information system are described. The scenario presented is that of a national Director of Veterinary Services taking his first steps in the computerisation of an epidemiology unit, but sub-national and international issues are also discussed. The administrative and management aspects are considered and the need to incorporate computers into a carefully designed and appropriate information system is emphasised. The principles of the specification of initial systems and their subsequent development are described; suggestions are made for the procurement and continuing support of both hardware and software. PMID- 1760577 TI - The OIE world animal disease information system. AB - The priority task of international collection and dissemination of information concerning diseases of animals by the OIE has three purposes: to alert countries threatened by an epizootic, to strengthen international cooperation on the control of animal diseases, and to facilitate international trade in animals and animal products. In order to improve the quantity and quality of information received, the OIE has organised seminars on the reporting of diseases of animals in most regions of the world. The authors show that these seminars have had very positive results. To achieve further progress, it is indispensable for every country to have a truly operational national system for animal health surveillance. Consequently, some technical assistance projects have been undertaken, beginning with Asia and Oceania, to examine the difficulties encountered by certain countries and to propose solutions. Activities of the various specialist commissions of the OIE have also led to improvement in the quality of information, particularly by defining, with greater precision, the concepts currently employed in connexion with diseases of animals (e.g. infection, disease, infected zone), and by standardising methods of diagnosis and of the preparation of biological products for veterinary use. Finally, a concise account is given of the development at the OIE Headquarters of an animal disease database, its mode of operation and various improvements which could be introduced to better satisfy the needs of Member Countries. PMID- 1760578 TI - Appropriate animal health information systems for nomadic and transhumant livestock populations in Africa. AB - Nomadic and transhumant livestock comprise the normative mode of production in the arid and semi-arid regions of Africa. By adopting management practices with high human labor and informational input, pastoral societies have adapted to innately high environmental variability. The Western veterinary model, which developed under sedentary conditions of production, has been unable to address herd health problems in African pastoral regions. By soliciting the participation of pastoral people, however, it is possible to develop an animal health information system that is technically appropriate, economically viable and socially acceptable. The organizational structure of appropriate information systems can furnish the framework for animal health delivery under pastoral conditions. PMID- 1760579 TI - Hepatitis of viral origin in Leporidae: introduction and aetiological hypotheses. AB - In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760580 TI - Molecular biology of the viral haemorrhagic disease virus of rabbits. AB - Viral haemorrhagic disease virus (VHDV) of rabbits is a small, nonenveloped DNA virus which contains a linear, single-stranded genome approximately 7,000 bases in length. The virions are icosahedral in symmetry, consisting of 180 subunits with pentamer-hexamer clustering. The capsid is composed of four structural polypeptides: VP1:60-61 kDa, VP2:54.7 kDa, VP3:52 kDa, and VP4:26-28 kDa. VP1 is a major structural polypeptide which constitutes approximately 54.7% of the total viral proteins. There are extensive antigenic relationships among the polypeptides. Haemagglutination activity is associated with the intact virions. The genome of the VHDV isolate strain (VHDV-NJ) is partially cloned, and 4.6 kb DNA fragment of restriction mapping has been determined, showing that there are few common restriction sites compared with the restriction site mapping of the parvoviruses. There are five viral-specific mRNA species, each coding for one of the five polypeptides identified by in vitro translation. The cDNA library from viral mRNA has been established. Southern blot hybridisation shows that, to some extent, H-I virus, minute virus of mice, porcine parvovirus and goose parvovirus share homology with VHDV. However, to clarify VHDV taxonomy, further efforts must be directed towards VHDV genome analysis. PMID- 1760581 TI - Adaptation of the viral haemorrhagic disease virus of rabbits to the DJRK cell strain. AB - Liver emulsion of rabbits which had died of viral haemorrhagic disease (VHD) was inoculated onto DJRK cell culture. After two passages, specific cytopathic effect was observed. Immunofluorescence was found in the nucleus at the early stage of infection and later also in the cytoplasm. The virus propagated in cell culture at the fifth, tenth and sixteenth passages was found to cause typical VHD. Electron microscopy showed that there were numerous virions in the infected cells. The cultured virus, inactivated with formaldehyde, could elicit haemagglutination inhibition antibodies in the inoculated rabbits and protect them against the challenge of virulent VHD virus. PMID- 1760582 TI - Clinical and pathological features of viral haemorrhagic disease of rabbits and the European brown hare syndrome. AB - The authors review the clinical, macro- and microscopical features, and pathogenesis of viral haemorrhagic disease (VHD) of rabbits and the European brown hare syndrome (EBHS). The two diseases share similar clinical and pathological manifestations involving an acute syndrome, sometimes accompanied by nervous and respiratory symptoms and epistaxis, and in all cases by severe hepatic damage and multifocal haemorrhages leading to fatal shock. The hepatic lesions (necrosis and inflammation) result from direct cytolytic and indirect microthrombotic effects of the causal agent. Endothelial lesions and a primary or secondary defect of coagulation factors are possible causes of the haemorrhagic syndrome. Typical lesions consist of necrotic hepatitis and congestion, haemorrhaging and oedema of the lungs and trachea. The histological and ultrastructural alterations of the liver are similar to those found in certain cases of acute fatal hepatitis in man. The high correlation between histologically typical hepatic findings and immunohistochemistry and immunoelectron microscopy is of diagnostic value. Both microscopic lesions and pathogenesis favour the unifying definition of "infectious necrotic hepatitis of Leporids" for the two disease entities. PMID- 1760583 TI - Viral haemorrhagic disease of rabbits in the People's Republic of China: epidemiology and virus characterisation. AB - Viral haemorrhagic disease (VHD) is a new and severe infectious disease of rabbits, with a high rate of morbidity and mortality. The disease occurs throughout the year, affecting only adult rabbits and not other domestic animals, fowls or laboratory rodents. The transmission is horizontal, by direct or indirect contact, and through all routes. There is no evidence of congenital infection or biological vectors. The causative agent, viral haemorrhagic disease virus (VHDV), is present in all tissues, excretions and secretions. It is an icosahedral and nonenveloped parvo-like virus. The genome, as determined by classical methods, high performance chromatography and in vitro synthesis of double-stranded DNA, is linear, single-stranded DNA. VHDV can agglutinate human erythrocytes at very high titres, irrespective of blood groups, and has a stable reaction to many physical and chemical factors. VHDV has been adapted to grow on rabbit kidney cell strain (DJRK) culture and to produce cytopathic effect (CPE). Inactivated cell culture can protect inoculated rabbits against virulent VHDV. The disease is now effectively controlled in the People's Republic of China, but has not yet been completely eradicated. PMID- 1760584 TI - Viral haemorrhagic disease of rabbits in Mexico: epidemiology and viral characterization. AB - A fatal disease of rabbits was first reported in the People's Republic of China in 1984. Since 1986, the disease has been reported in most countries of Europe and in the Republic of Korea. In 1989 a similar disease, presumably linked to the importation of rabbit meat from the People's Republic of China, spread rapidly through ten states in Mexico; it was eradicated during the same year by "stamping out" measures. In Mexico, as was the case in other outbreaks, morbidity and mortality reached 80-90% with few clinical signs. In pathogenesis studies, the primary sites of replication were in the small intestinal crypt and villous epithelium, hepatocytes and splenic lymphocytes. Many organs, including the lung and kidney, contained acutely infarcted tissue and haemorrhages resulting from a terminal disseminated intravascular coagulopathy. The disease and the characteristics of the virus isolated in Mexico are similar to isolates from Europe and the Republic of Korea. The comparative morphologic, from Europe and the Republic of Korea. The comparative morphologic, immunologic, and in situ nucleic acid hybridization evidence for a parvovirus aetiology are summarized. PMID- 1760585 TI - Epidemiology and diagnosis of the European brown hare syndrome in Scandinavian countries: a review. AB - Outbreaks among European brown hares (Lepus europaeus, Pallas) of a fatal disease associated with severe liver damage have occurred in Sweden since the beginning of the 1980s. The disease, called the European brown hare syndrome (EBHS), was recognised in Denmark in 1982 and is today widespread in Denmark and southern Sweden. It has not been reported in Norway or Finland. Two species of hares are affected in Sweden, the European brown hare and the varying hare (Lepus timidus, Linnaeus). EBHS occurs both in free living and farmed hares. The disease is clearly seasonal, occurring most frequently in October, November and December. A virus related to the viral haemorrhagic disease of rabbits virus has been shown to cause EBHS. All attempts to isolate the virus in cell culture have been unsuccessful. Diagnosis can be made by histopathology and detection of the virus in organ homogenates by haemagglutination, negative staining electron microscopy and enzyme-linked immunosorbent assay (ELISA). Antibodies can be detected early by haemagglutination inhibition and ELISA. PMID- 1760586 TI - Viral haemorrhagic disease of rabbits: vaccination and immune response. AB - Results are presented for the large-scale use of a tissue vaccine, inactivated with beta-propiolactone and containing aluminium hydroxide adjuvant, against viral haemorrhagic disease of rabbits. The kinetics of haemagglutination inhibiting antibodies over eighteen months, the response of vaccinated animals to challenge infection with field virus between six and fifteen months after vaccination, the serological response to revaccination, and the immunological mechanisms involved in primary vaccination and revaccination were investigated. PMID- 1760587 TI - Vaccination against and immune response to viral haemorrhagic disease of rabbits: a review of research in the People's Republic of China. AB - Viral haemorrhagic disease (VHD) of rabbits is an acute entity with high mortality which affects adult rabbits. Several vaccines have been developed in China and extensive use of these vaccines in the field has controlled the spread of the disease. Formalin inactivated tissue vaccine induces solid immunity on the third to fourth day post vaccination and immunity lasts for at least six months. The oil-emulsion tissue vaccine which has been developed has longer lasting potency. Successful adaptation of VHD virus (VHDV) to cultured cells and preliminary immunisation will provide the possibility of large-scale production of cell-cultured virus vaccine. Passive, emergency immunisation with hyperimmune antiserum provides short-term protection of threatened rabbits as well as treatment of infected rabbits in the field. Histopathological and pathophysiological studies reveal that immune cells and organs are the most affected targets in infected rabbits; owing to the damage to the endothelial system of blood vessels, extensive disseminated intravascular coagulation (DIC) occurs in the parenchymal tissues. Destruction of the immune system and the occurrence of DIC lead to acute illness and sudden death post infection. Experimental immunological studies demonstrate that the induction of rapid immunity is coordinated by macrophages and T and B lymphocytes in the initial, post-immunisation stage, whereas humoral immunity plays the main role in long term protection against VHDV infection. The positive association of post vaccination protection with haemagglutination inhibition antibody can also be observed. Interferon probably takes effect as an anti-VHDV agent soon after vaccination. PMID- 1760588 TI - Systematic morphogenesis of the viral haemorrhagic disease virus in infected rabbits and in adapted cell culture. AB - The morphogenesis of viral haemorrhagic disease virus (VHDV) of rabbits in infected cell cultures and in tissues and cells from infected animals has been observed systematically by electron microscopy. Viral particles have been found to assemble through a condensation process within the nucleus of infected cells, having passed partially into the cytoplasm through disrupted nuclear membranes, enlarged nuclear pores or perinuclear space. Late in infection, both mature and immature virions are observed in the cytoplasm; these are often aggregated or interspersed and remain cell-associated long after infection. Release of the virus occurs when the cell finally lyses. In studies of the localisation and development of VHDV antigens, the viral antigens have been observed to appear first in the nucleus of infected cells and often thereafter in the cytoplasm. This finding is very similar to observations made by electron microscopy. PMID- 1760589 TI - Application of control measures against viral haemorrhagic disease of rabbits in the Czech and Slovak Federal Republic. AB - The first outbreaks of viral haemorrhagic disease (VHD) of rabbits were reported from eastern Slovakia in 1987. In 1988, the infection spread throughout the Czech and Slovak Federal Republic. Electron microscopy was used by the Veterinary Research Institute in Brno to diagnose the disease during the early stage of infection. At present, the regional laboratories of the veterinary investigation services use the haemagglutination and the direct immunofluorescence tests as the principal methods to demonstrate the causal agent. Indirect immunofluorescence and immunoperoxidase techniques have been developed to demonstrate VHD virus, while the enzyme-linked immunosorbent assay (ELISA) has been used to detect antibodies. Diagnostic kits, allowing a wide use of these methods, are now available commercially. Two types of inactivate vaccines were developed and produced in 1988 and 1989. VHD is controlled by vaccination of exposed rabbit colonies. This is accompanied by other preventive and protective measures, directed by district veterinary officers following instructions from federal authorities. PMID- 1760590 TI - The measurement of nucleoside deaminases by high performance liquid chromatography and their use in clinical chemistry. AB - The measurement of the nucleoside deaminases--cytidine deaminase, guanosine deaminase and adenosine deaminase--by reversed phase high performance liquid chromatography is reviewed. The clinical value of assaying the enzyme activity is discussed for each of these enzymes. Both cytidine deaminase and adenosine deaminase measurements have proven clinical value, although the use of the assay of cytidine deaminase in the diagnosis of pre-eclampsia is probably not helpful. PMID- 1760591 TI - A high performance liquid chromatographic method for the quantitation of flecainide in plasma. AB - A routine high performance liquid chromatographic method for the rapid determination of flecainide (Flecaine), using a novel internal standard, N methylflecainide, has been developed. After deproteinization of spiked samples, flecainide was totally recovered at neutral pH. Flecainide and the internal standard were separated on a reversed phase XL 3 microns ODS column using 10 mM phosphate buffer, pH 3.0: acetonitrile (70:30) as mobile phase, in less than 10 min. With spectrofluorometric detection, the limit of quantitation for flecainide was 10 ng/mL. Intra- and inter-assay precision variations were 0.24% and 1.4%. PMID- 1760592 TI - Study of the solid phase extraction of pentoxifylline and its major metabolite as a basis of their rapid low concentration gas chromatographic determination in serum. AB - A gas-liquid chromatographic method for the determination of pentoxifylline and its secondary alcohol metabolite in serum has been developed. The method is based on the combination of solid phase extraction, capillary column separation and nitrogen-phosphorus detection of the analytes. Optimization of the solid phase extraction conditions permitted a low concentration determination, with limits of determination of 2 ng/mL and 10 ng/mL for pentoxifylline and its metabolite, respectively. The simplicity and rapidity of the extraction step was preserved. PMID- 1760593 TI - Disopyramide analysis using REMEDi: comparison with EMIT and conventional high performance liquid chromatographic methods. AB - REMEDi (Rapid EMErgency Drug identification; Bio-Rad) is an automated high performance liquid chromatographic (HPLC) system designed to detect, identify and measure a range of basic and neutral drugs in 0.5-1.0 mL of urine or plasma/serum. We have evaluated REMEDi in the analysis of the antiarrhythmic drug disopyramide in patient samples. The specimens were also analysed by a conventional HPLC method, based on solvent extraction and UV detection (254 nm), and by EMIT. There were good correlations between the results obtained with each method (r = 0.91 or greater). REMEDi gave a lower mean result than EMIT [means +/ SD (mg/L): REMEDi 2.64 +/- 1.10, EMIT 3.14 +/- 1.51; t = 4.0, p less than 0.01; n = 25], but there were no other significant differences in mean results. The principal disopyramide metabolite, mono-N-desalkyldisopyramide, did not interfere in any method. Clearly REMEDi can be used for therapeutic drug monitoring of disopyramide provided enough sample is available. PMID- 1760594 TI - Rescuers' psychological responses to disasters. PMID- 1760595 TI - Lessons of Chernobyl. PMID- 1760597 TI - The health strategy and the hole at the centre. PMID- 1760596 TI - Artificial blood. PMID- 1760598 TI - German haemophilic patients infected with HIV. PMID- 1760599 TI - Prison policies on HIV under review. PMID- 1760600 TI - Childhood leukaemia and poliomyelitis in relation to military encampments in England and Wales in the period of national military service, 1950-63. AB - OBJECTIVE: To determine if any excess of childhood leukaemia was associated with the large and increasing numbers of national military servicemen in 1949 and 1950, particularly in rural districts. This would be a further test of the hypothesis that childhood leukaemia can originate in an infection, the transmission of which is facilitated by an increased number of unaccustomed contacts in the community. DESIGN: Rural and urban districts, aggregated by county, were ranked by proportion of servicemen, and five groups containing similar numbers of children were created. In addition, individual local authority districts were ranked and grouped in tenths. Mortality from childhood leukaemia 1950-3 was examined in these groups. Data on infectious diseases were also examined, as well as data on leukaemia in later periods. SETTING: England and Wales. SUBJECTS: Children aged under 15 years. RESULTS: In 1950-3 but not subsequently a significant excess of leukaemia in children under 15 was found in the fifth of county groupings with the highest proportions of servicemen. This was due mainly to a significant excess in children under 2 years (and especially in those under 1 year) in rural districts. It was confirmed among the tenth of local authority districts with the highest proportion of servicemen. These rural areas showed significantly more notifications of, and deaths from, poliomyelitis among children than the rural average. CONCLUSIONS: The findings support the infection hypothesis. That the excess of leukaemia was greatest in children under 1 year suggests transmission of infection among adults and thence to the fetus. The pattern of spread of poliomyelitis may also have been influenced by the presence of large numbers of servicemen. PMID- 1760601 TI - A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia. AB - OBJECTIVE: To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia. DESIGN: Randomised study of two treatment groups with a minimum follow up of nine months. SETTING: Royal Berkshire Hospital, Reading. SUBJECTS: 51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy. TREATMENT: Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons. MAIN OUTCOME MEASURES: Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection. RESULTS: Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year. CONCLUSION: For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection. PMID- 1760602 TI - How do patients with HIV perceive their general practitioners? AB - OBJECTIVE: To study the perceptions of patients with HIV of their general practitioners in terms of knowledge, abilities, confidence, and satisfaction. DESIGN: Questionnaire survey of inpatients, outpatients, and members of a self help group. SETTING: Two city hospitals, three outpatient clinics, and one AIDS self help group in Munich and Berlin, Germany. SUBJECTS: All 402 patients available between 1 September 1988 and 31 May 1989. MAIN OUTCOME MEASURES: General practitioners' attitudes towards the patients' HIV status; patients' experience of treatment rejection; reception in the general practitioner's office; the doctor's perceived knowledge about HIV and AIDS. RESULTS: 394 of 402 patients consented to interview; 87% were registered with a general practitioner and 91% of those indicated that the doctor was aware of their HIV diagnosis. The overwhelming majority of patients (94%) had a friendly or at least neutral reception in the general practitioner's surgery and only six patients' general practitioner changed his or her behaviour for the worse because of the HIV diagnosis. Two thirds of patients said they would consult first with their primary care doctor for a physical problem, but only 13% would do so for psychological problems. Over a third of the patients did not routinely inform other doctors or medical staff about their HIV status, but there was no significant correlation between this concealment and ever having been rejected by a doctor (7%) or a dentist (12%). CONCLUSION: Most patients expressed a high degree of satisfaction with their general practitioners in terms of confidential issues, attitudes, knowledge, and management. PMID- 1760603 TI - Genitourinary tract infections in pregnancy and low birth weight: case-control study in Australian aboriginal women. AB - OBJECTIVE: To investigate the association between genital and urinary tract infections in pregnant Aboriginal women and low birth weight. DESIGN: Retrospective case-control study controlling for potential confounding variables. SETTING: Western Australia from 1985 to 1987. SUBJECTS: All Aboriginal women (n = 269) who had given birth to singleton infants weighing 2250 g or less (cases), and 269 randomly selected Aboriginal women who had given birth to singleton infants weighing 3000 g or more (controls). MAIN OUTCOME MEASURES: Proportions of women in case and control groups who had had genital and urinary tract infections; odds ratios for low birth weight when genitourinary tract infection was present; population attributable fraction of low birth weight to genitourinary tract infection. RESULTS: At the time of delivery 51% of women in the case group (109/215) had genitourinary tract infections compared with 13% of controls (35/266). After controlling for potential confounding variables the odds ratio for giving birth to infants weighing 2250 g or less when genitourinary tract infection was present was 4.0 (95% confidence interval 2.3 to 7.0). The proportion of infants with low birth weight attributable to genitourinary tract infection in the whole population of Aboriginal women was 32% (95% confidence interval 17% to 49%). CONCLUSIONS: There was a strong association between low birth weight and the presence of genitourinary tract infections in Aboriginal women both during pregnancy and at the time of delivery. A community intervention trial of screening and treatment of genitourinary infections in this population is recommended. PMID- 1760604 TI - Risk of epilepsy after febrile convulsions: a national cohort study. AB - OBJECTIVE: To identify children with febrile convulsions, classify their febrile convulsions into simple and complex, and determine the number and type of subsequent afebrile seizures in those children. DESIGN: National population based study. SETTING: United Kingdom. SUBJECTS: 16,004 neonatal survivors born during one week in April 1970. MAIN OUTCOME MEASURES: Information about febrile and afebrile seizures obtained from questionnaires at 5 and 10 years of age and from hospital records. RESULTS: Information was available for 14,676 of the cohort children. 398 (2.7%) of them had had at least one febrile convulsion. 16 children were known to be neurologically or developmentally abnormal before the first attack. Of the remaining 382 children, 305 had had a simple first febrile convulsion and 77 a complex first febrile convulsion. Thirteen of the 382 had had one or more afebrile seizures, nine of whom had developed epilepsy (recurrent afebrile seizures). A higher proportion of children with complex febrile convulsions (6/95) rather than simple febrile convulsions (3/287) developed epilepsy, the risk being highest for those who had had focal febrile convulsions (5/17; chi 2 = 39.9, p less than 0.001). Three of the 32 children who had prolonged febrile convulsions developed afebrile complex partial seizures. CONCLUSIONS: The risk of epilepsy after febrile convulsions is much less than reported in many hospital studies, and if febrile convulsions cause brain damage that leads to later epilepsy this is a rare occurrence. PMID- 1760605 TI - Severe cystitis associated with tiaprofenic acid. PMID- 1760606 TI - Does competence of general practitioners predict their performance? Comparison between examination setting and actual practice. AB - OBJECTIVE: To study the differences and the relation between what a doctor actually does in daily practice (performance) and what he or she is capable of doing (competence) by using national standards for general practice. DESIGN: General practitioners were consulted by four standardised (simulated) patients portraying four different cases during normal surgery hours. Later the doctors participated in a controlled practice test, for which they were asked to perform to the best of their ability. In the test they saw exactly the same standardised cases but in different patients. The patients reported on the consultations. SETTING: Province of Limburg, the Netherlands. SUBJECTS: 442 general practitioners invited by a letter. 137 (31%) agreed to participate, of whom 36 were selected and visited. MAIN OUTCOME MEASURES: Number of actions taken during the consultations across complaints and for each category of complaint: the competence and performance total scores. Combination of scores with duration of consultations (efficiency-time score). Correlation between scores in the competence and performance part. RESULTS: Mean (SD) total score across complaints for competence was 49% higher than in the performance test (81.8 (11) compared with 54.7 (10.1), p less than 0.0001). The Pearson correlation across complaints between the competence total score and the performance total score of the participating physicians was -0.04 (not significant). When efficiency and consultation time of the consultations were taken into account, the correlation was 0.45 (p less than 0.01). CONCLUSIONS: Assessment of competence under examination circumstances can have predictive value for performance in actual practice only when factors such as efficiency and consultation time are taken into account. Below standard performance of physicians does not necessarily reflect a lack of competence. Performance and competence should be considered as distinct constructs. PMID- 1760607 TI - The Hillsborough tragedy. PMID- 1760609 TI - ABC of vascular diseases. Convalescent problems in arterial surgery. PMID- 1760608 TI - Doctor-patient communication: the Toronto consensus statement. PMID- 1760610 TI - Health and the environment. Waste disposal: fresh looks at a rotting problem. PMID- 1760612 TI - Doctors convicted of manslaughter. PMID- 1760611 TI - Medicine in Europe. European health challenges. PMID- 1760613 TI - Glasgow coma scale and gag reflex. PMID- 1760614 TI - Rugby injuries. PMID- 1760615 TI - Chorionic villus sampling. PMID- 1760616 TI - Oral and intravenous rehydration therapy. PMID- 1760617 TI - Auditing necropsies. PMID- 1760618 TI - Communicating necropsy results. PMID- 1760619 TI - Corticosteroids and tuberculosis. PMID- 1760620 TI - Health of the nation. PMID- 1760621 TI - Zidovudine after occupational exposure to HIV. PMID- 1760622 TI - Use of thalidomide in leprosy. PMID- 1760623 TI - Animal experimentation. PMID- 1760624 TI - Seafarers and HIV infection. PMID- 1760625 TI - Growth failure in children after total body irradiation preparative for bone marrow transplantation. PMID- 1760626 TI - Growth hormone therapy following bone marrow transplantation in childhood. PMID- 1760627 TI - Pubertal development and fertility in children after bone marrow transplantation. PMID- 1760628 TI - Endocrine problems in children after bone marrow transplant for hematologic malignancies. The Long-term Follow-up Team. PMID- 1760629 TI - Gonadal function after bone marrow transplantation in adult male and female patients. PMID- 1760630 TI - Late effects in bone marrow transplanted patients--a multicenter study supported by EBMT and EULEP. PMID- 1760631 TI - Total body irradiation in the conditioning regimen for hematological malignancies. AB - The role of Total Body Irradiation (TBI) is well defined in the conditioning regimen for BMT, but in pediatric malignancies there are some particular points of discussion, due to the side effects of irradiation. As alternative methods have been described, as Busulfan based regimens, a critical balance between efficacy and toxicities has to be considered in this subset of patients. PMID- 1760632 TI - Busulfan as part of conditioning regimen for bone marrow transplantation in children. PMID- 1760633 TI - Is orchiectomy indicated before BMT in childhood ALL? PMID- 1760634 TI - Hormonal and psychologic assessment in LLA patients after bone marrow transplant. AB - Four adolescent males were submitted to hormonal and psychological evaluation 3-8 years after bone marrow transplant. All presented testicular failure, two were submitted to orchiectomy. Androgen replacement therapy was begun at 13 yr 7 mo-17 yr. A psychological evaluation has been performed. Orchiectomy and insertion of artificial testicles do not seem to have affected patients' psychological situation. Individual differences have been found due to many causes. PMID- 1760635 TI - Ethical and legal problems of orchiectomy. PMID- 1760636 TI - A proposal for multicentric schedule for follow-up of bone-marrow transplanted children. PMID- 1760637 TI - Precocious puberty following BMT. PMID- 1760638 TI - Evaluation of late side-effects after bone marrow transplantation in children with leukemia. PMID- 1760639 TI - Cyclic sex hormone replacement therapy in women undergoing allogeneic bone marrow transplantation: aims and results. PMID- 1760640 TI - Growth pattern in children after allogenic bone marrow transplantation. PMID- 1760641 TI - Gonadal function in adolescents receiving different conditioning regimens for bone marrow transplantation. PMID- 1760642 TI - Pubertal development after bone marrow transplantation in adolescents. PMID- 1760643 TI - Prospective study of endocrine side-effects following bone marrow transplantation in childhood. PMID- 1760644 TI - Prophylactic orchiectomy after bone marrow transplantation for boys with acute lymphoblastic leukaemia and previous testicular relapse. PMID- 1760645 TI - Approaches to the evaluation of growth and growth disorders in children after bone marrow transplantation (BMT). AB - Since impaired growth may occur as a long--term consequence in children treated with BMT this aspect of development needs particular attention for various reasons. Primarily, in each affected child parameters relevant for the evaluation of growth need to be documented regularly from the beginning in a prospective mode. In addition, treatment protocols should contain elements of a standardized follow-up for the documentation and evaluation of the endocrine, the nutritional and the emotional situation of the patient. This will eventually allow us to define--and hopefully avoid--adverse elements within complex treatment modalities -including BMT--for various malignant diseases. Thus it will be possible to develop a rational approach for the therapy of persistent adverse events following attempts of treatment primarily directed to ensure survival. PMID- 1760646 TI - Growth in pubertal children after bone marrow transplantation. PMID- 1760647 TI - Growth and endocrine assessment in children undergoing bone marrow transplant: the 'G. Gaslini' experience. PMID- 1760648 TI - Oral and dental status in leukemic children treated with bone marrow transplantation. PMID- 1760649 TI - Pancreatic beta cell function in children and adolescents after bone marrow transplantation. PMID- 1760650 TI - Growth in homozygous beta-thalassemia after bone marrow transplantation. AB - In 8 homozygous beta-thalassemic patients, aged between 1.9 and 18 years, that received bone marrow transplantation (BMT), a longtidinal study of growth before and after BMT and relative Height Standard Deviation Score (SDS), has been performed. In all patients, also after BMT, a progressive growth retardation has been observed except in a case who presented serum ferritin levels in a normal range for age. The study shows that iron depletion must be continued, even after BMT, in those subjects that have after bone marrow transplantation high serum ferritin levels and short stature. PMID- 1760651 TI - Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia -a European survey. EBMT Working Party on ABMT. PMID- 1760652 TI - Autogous bone marrow transplantation for childhood acute myeloid leukemia--a European survey. EBMT Working Party on ABMT. PMID- 1760653 TI - Neurochemical mechanisms of recovery from peripheral vestibular lesions (vestibular compensation) AB - This paper reviews the literature relating to the neurochemical basis of vestibular compensation, a process of behavioral recovery which occurs following the removal of afferent input from one labyrinth (unilateral labyrinthectomy, UL). Although vestibular compensation is known to be correlated with a return of resting activity to the vestibular nucleus (VN) ipsilateral to the UL (the deafferented VN), the neurochemical mechanisms by which this neuronal recovery occurs, are unknown. At present, there is little evidence to support the hypothesis that denervation supersensitivity of excitatory amino acid, dopamine, norepinephrine or acetylcholine receptors in the deafferented VN, is responsible for vestibular compensation: binding studies for glutamate or acetylcholine do not support an upregulation of these receptor types. However, changes in the affinity or efficacy of these receptor complexes cannot be ruled out. There are still many neurotransmitter systems, such as serotonergic and histaminergic systems, which have not been investigated in relation to vestibular compensation. In several species it has been shown that treatment with adrenocorticotropic hormone, fragment 4-10 (ACTH-(4-10], can accelerate vestibular compensation. It is not clear how these drugs exert their effects. In vitro electrophysiological studies have shown that VN neurons are capable of generating resting activity in the absence of their normal afferent inputs and it is possible that these neurons have pacemaker-like membrane characteristics which contribute to the regeneration of activity following UL. Recent biochemical studies have revealed changes in the phosphorylation patterns of a number of proteins during compensation. The possible relationship between these phosphorproteins and the synaptic or membrane changes which are responsible for vestibular compensation remains to be determined. PMID- 1760654 TI - The messages in optic nerve fibers and their interpretation. AB - Spike discharges are the principal carriers of information in the nervous system. Although both the ionic and the molecular mechanisms of spike generation have been studied extensively, the methods for analyzing a spike train that are currently employed have not changed much from those in use 20 years ago. There is an apparent need for a refinement of the methods used to analyze spike trains. We present here a summary of our recent results of an analysis of spike trains from retinal ganglion cells that is based on Wiener's theory of non-linear analysis or white-noise analysis. We found that spike trains carry, at least to a second order approximation, as much information as is carried by the ganglion cell's postsynaptic potential (PSP). There is no loss of information when an analog signal, PSP, is converted into a point process, namely, spike discharges. It is indeed possible to predict the cell's PSP from a spike train. This finding has two important implications. First, the neuron network in the retina produces a PSP, the dynamics of which are optimal for triggering a spike discharge, or conversely, the spike-generation mechanism is optimized to match the dynamics of the network. The external stimulus that is optimal for production of a ganglion cell discharge is represented as the cell's PSP. Second, there is structure encoded within the spike train; information on a second-order non-linearity is encoded by the relative timing of two consecutive spike discharges. Coding of non linearity into a spike train is an efficient means of signal compression and is an important aspect of neurophysiology. PMID- 1760655 TI - Taurine: retinal function. AB - The status and potential functions of taurine in the retina have been reviewed. Taurine is present in high concentrations in the retina of all species tested, while the retinal concentrations of the enzymes necessary to synthesize taurine are presumed to vary among those species. The documented low activity of cysteinesulfinic acid decarboxylase, a key enzyme in taurine biosynthesis, in the livers of the cat, monkey and human possibly reflect low activity in their retinas, indicating reliance on the diet as an important source of taurine. Both high- and low-affinity binding proteins and uptake systems have been described for taurine in retinal tissue. Evoked release of taurine by light and other depolarizing stimuli have been well documented. Retinal pathologies including diminished ERGs and morphologic changes have been reported for animals and man deficient in taurine. Possible functions for taurine in the retina include: (1) protection of the photoreceptor - based on the shielding effects of taurine on rod outer segments exposed to light and chemicals; (2), regulation of Ca2+ transport - based on the modulatory effects of taurine on Ca2+ fluxes in the presence and absence of ATP; and (3) regulation of signal transduction - based on the inhibitory effects of taurine on protein phosphorylation. PMID- 1760656 TI - Learning and memory. FESN Study Group. PMID- 1760657 TI - Home care in the 1990s. PMID- 1760658 TI - Is the implantable cardioverter-defibrillator cost-effective? PMID- 1760659 TI - Growing points in psychiatric genetics. PMID- 1760660 TI - The Chest, Heart and Stroke Association. PMID- 1760661 TI - Neuroanatomy of the upper limb. PMID- 1760662 TI - Risks of unnecessary X-rays are widely understood. PMID- 1760663 TI - The changing role of high dependency units. PMID- 1760664 TI - Caution urged in the use of DC cardioversion. PMID- 1760665 TI - Conduct of the examination in child sexual abuse. PMID- 1760666 TI - Need for more training in the use of the ventouse. PMID- 1760667 TI - Strange sequela of unexplained failure of a spinal anaesthetic. PMID- 1760668 TI - Problems of multiple pregnancy. AB - There has been a sharp increase in the number of multiple births, particularly triplets and higher order births, in recent years (Botting et al, 1990). Perinatal mortality and morbidity are more frequent in multiple pregnancies than in singleton pregnancies. Greater understanding of the biological phenomenon of multiple pregnancy and perinatal care strategies directed at specific problems should improve the outcome. PMID- 1760669 TI - Paraphrenia revisited. AB - Paranoid disorders of late life, commonly known as paraphrenia, are not uncommon. This article reviews the history of the concept, the classification, the possible risk factors implicated in causation and the natural history of the disorder. Evidence suggests that paraphrenia is distinct from schizophrenia and that an organic substrate probably exists in most cases. PMID- 1760670 TI - Chronic lymphocytic leukaemia. AB - Chronic lymphocytic leukaemia is the commonest of the leukaemias and occurs most often in the elderly. The identification of presenting features that correlate adversely or favourably with survival has allowed the rational development of new treatment strategies. PMID- 1760671 TI - How and when to investigate syncope. AB - Recurrent syncope is a distressing phenomenon and may be very difficult to treat where the cause remains obscure. A methodical approach to investigation will often be fruitful when proper emphasis is given to thorough clinical assessment and simple investigations. Where these are normal, head-up tilt testing will often diagnose 'malignant vasovagal syndrome'. PMID- 1760672 TI - A surprising case of hypertension. PMID- 1760673 TI - Moral principles in withdrawing basic life support from patients in the persistent vegetative state. AB - Patients in a state of persistent vegetation or 'cognitive death' are an emotional drain on their family, and a financial drain on a society with limited resources. In this article, society's responsibility towards these patients and the moral and ethical issues involved in the withdrawal of fluid and nutrition are discussed. PMID- 1760674 TI - Home ventilation. AB - Home ventilation has become practical recently because of improvements in the equipment available to support respiration in the long term. It is especially effective in neuromuscular and skeletal disorders, but may also have a limited place in chronic lung diseases. Both positive- and negative-pressure ventilators may be suitable for home ventilation. PMID- 1760675 TI - Percutaneous insertion of Hickman-type catheters. AB - Hickman lines may be used for long-term venous access in patients having chemotherapy, bone marrow transplantation, parenteral nutrition, or in others needing prolonged venous access. This article describes the technique of percutaneous insertion, some of the problems that may be encountered at insertion, and ways of minimizing these problems. PMID- 1760676 TI - The sail sign. AB - Radiological terminology includes a number of interesting and often amusing terms intended to help us understand and remember the pathological abnormality being described. What radiological sign is illustrated in Fig. 1 and what condition does it represent? PMID- 1760677 TI - Lateral sinus abscess: the empty delta sign. PMID- 1760678 TI - A curious case of catatonia. PMID- 1760679 TI - The opiates debate. PMID- 1760680 TI - Anticholinergic drugs in anaesthesia. PMID- 1760681 TI - Immunotherapy for cancer. PMID- 1760682 TI - Use of the appendix in reconstructive surgery: a case against incidental appendicectomy. AB - Ignored for years, the appendix is once again being promoted as having useful surgical potential, notably in the management of incontinence. Incidental and prophylactic appendicectomy with their established complications become less easy to justify as the incidence of appendicitis declines. The role of the appendix in reconstructive surgery is reviewed, with particular reference to urinary reconstruction and to the treatment of chronically constipated or faecally incontinent children by use of the antegrade continence enema. PMID- 1760683 TI - Peptide growth factors and wound healing. AB - Growth factors and cytokines are important signal transducers in wound microenvironments. Experimental data are accumulating rapidly which demonstrate their ability to influence populations of polymorphs and macrophages to migrate to the wound, subsequently to be replaced by synthetic cells which produce collagen and matrix; these events are controlled sequentially at cell receptor level by a variety of locally delivered (paracrine and autocrine) peptides. Preliminary results from clinical trials using recombinant human growth factors to improve cutaneous healing are encouraging. Current research aims to produce growth preparations which can be applied to a wound to accelerate healing. PMID- 1760684 TI - Sutureless intestinal anastomoses. AB - Sutureless intestinal anastomoses can be achieved either by compression, where two inverted rings of bowel are compressed by a hollow circular device that subsequently sloughs away and is passed anally, or by the use of tissue glues or laser welding. Compression devices used clinically with success are the Valtrac biofragmentable anastomotic ring, the polypropylene rings described by Rosati and the AKA guns. Glued anastomoses have only been used in animals and seem to be unsafe. However, laser-welded intestinal anastomoses appear highly promising in experimental studies and further development of this technique is warranted. PMID- 1760685 TI - Recurrence of colorectal cancer after sutured and stapled large bowel anastomoses. AB - The purpose of this study was to compare surgical stapling and manual suturing techniques with respect to the incidence of tumour recurrence in patients with colorectal cancer: 294 patients undergoing potentially curative resections for colorectal cancer were randomly allocated to receive sutured (n = 142) or stapled (n = 152) anastomoses. The mean (s.e.m.) incidence of tumour recurrence at the end of 24 months was 29.4(4.4) per cent in the sutured group, compared with 19.1(3.9) per cent in the stapled group (P less than 0.05). The corresponding rates for cancer-specific mortality at 24 months were 22.3(4.1) per cent and 10.9(3.0) per cent respectively (P less than 0.01). A multiple regression analysis revealed that the influence of anastomotic technique on recurrence and mortality rate was independent of tumour stage. These results suggest that in colorectal cancer surgery the use of stapling instruments for anastomotic construction could be associated with a reduction in the incidence of recurrence and mortality rate by as much as 50 per cent. PMID- 1760686 TI - Abdominal injuries in the war wounded of Afghanistan: a report from the International Committee of the Red Cross Hospital in Kabul. AB - This report is from the hospital opened by the International Committee of the Red Cross, in Kabul, which receives acute war-wounded patients from the Afghanistan conflict. Of more than 1000 operations carried out by the New Zealand team in a 6 month period, there were 70 laparotomies for penetrating wounds. These injuries were dealt with by established surgical techniques. The main area of controversy was the management of colonic wounds where the recent trend away from mandatory colostomy was followed by good results. Selective primary repair was achieved in 16 of 27 patients with colonic injury with no mortality and minimal morbidity. The right colon was considered particularly favourable for primary anastomosis. The overall mortality rate for all laparotomies was 13 per cent, with injuries to the liver, major veins and rectum particularly being fatal. There were eight negative laparotomies. PMID- 1760687 TI - Glutamine-enhanced enteral diet improves nitrogen balance without increasing portal ammonia. AB - Following surgical stress the jejunum actively metabolizes endogenous glutamine, a non-essential amino acid, to produce alanine and ammonia, which augments substrate flow to the liver at a time when oral intake of nutrients is decreased. Oral glutamine supplementation theoretically may modify the response to injury. This study was designed to demonstrate the role of the jejunum in postinjury glutamine metabolism and to evaluate the influence of enteral glutamine supplements on nitrogen and ammonia metabolism after laparotomy and bowel resection in dogs. Oral glutamine in the presence of an intact small bowel significantly improved nitrogen balance (461 mg kg body-weight-1 day-1) compared with a control diet (-370 mg kg-1 day-1) (P less than 0.05, analysis of variance). Removal of the proximal small bowel prevented this beneficial effect of glutamine (-507 mg kg-1 day-1). Glutamine-supplemented and control diets were associated with similar portal ammonia concentrations throughout the study. PMID- 1760688 TI - Hypoxaemia and postoperative pulmonary complications. PMID- 1760689 TI - Mucosal function after ileal mucosal fenestration and colonic autotransplantation. AB - A method of small bowel mucosal augmentation called ileal mucosal fenestration and colonic autotransplantation (IMFCA) was devised and tested in pigs. In this technique, a vascularized mucosal graft was harvested from a 12-cm ileal loop, fenestrated by serial incision and then expanded to 20 cm. A 20-cm colonic loop was isolated and surgical mucosectomy was carried out. The fenestrated ileal mucosal graft was then autotransplanted into the prepared colon and the resulting composite structure was exteriorized as a Thiry-Vella loop. With this technique, ileal mucosal fenestrations healed by lateral epithelial in-growth, giving a new mucosal continuum within the recipient colon. At 60 days after surgery, the surface area of transplanted mucosa exceeded that within the original ileal loop by approximately 85 per cent. At this time, the transplanted mucosa had morphology and capacity for Na(+)-dependent glucose transport which were indistinguishable from those of control ileal mucosa. PMID- 1760690 TI - Secondary surgery for liver trauma. AB - Over a 10-year period from 1980, 46 patients with liver injuries were referred after primary admission to other hospitals. Previous surgery had been performed in 40 cases and the predominant reasons for referral were uncontrollable bleeding and postoperative sepsis with biliary leakage. Of 30 such cases, 19 were treated by liver resection; all were of a limited nature and no major hepatectomies were performed. Only two deaths occurred in these patients and this low mortality rate supports our conservative approach to liver trauma. Other reasons for referral were late biliary stenosis, complicated penetrating injury and intrahepatic haematoma. Three cases were referred with postoperative hepatic failure; two responded to resection of infected necrotic tissue and liver transplantation was attempted in the third. Injuries to liver segments 6 and 7 were those most frequently referred for assistance with bleeding, and all patients were safely transferred after intra-abdominal packing. This injury is particularly suitable for resection by segmentectomy rather than a formal hepatectomy, which has been associated with a high mortality rate in trauma cases. Further patients with intractable injuries might be salvaged by liver transplantation. PMID- 1760691 TI - Sarcoma induced by radiotherapy after breast conservation surgery. PMID- 1760692 TI - A safe new procedure for high-risk patients with symptomatic gallstones. AB - Cholecystectomy is associated with an appreciable mortality rate in elderly high risk patients. Patients aged over 60 years with symptomatic gallstones, at high operative risk, underwent cholecystotomy under local anaesthesia through a 3-cm incision. Stones were removed and clearance was demonstrated endoscopically and by tube cholecystography. Catheter drainage was continued for 7 days until a further cholecystogram confirmed clearance. The procedure was attempted in 26 patients with concomitant cardiovascular, respiratory or malignant disease. Successful removal of all gallbladder stones was possible in 24 patients. Four patients had common bile duct stones demonstrated on cholecystography, all of which were successfully treated by endoscopic sphincterotomy. All patients are symptom-free at a mean follow-up of 36 weeks with no recurrent stones on ultrasonography. PMID- 1760693 TI - Cystic duct obliteration and gallbladder mucosal destruction: a feasible alternative to cholecystectomy. AB - 'Chemical cholecystectomy' has been proposed as an alternative to removal of the gallbladder. This study assessed cystic duct obliteration using bipolar electrocoagulation (with sham cannulation controls) and gallbladder mucosal treatment with tetracycline (or saline controls) in 29 mongrel dogs. Cystic duct obstruction was assessed by tube cholecystography at day 14, and epithelial damage by histology at day 42. Electrocoagulation by duct diathermy effectively occluded the cystic duct in 14 of 19 animals; however, this was associated with mucocele formation unless mucosal treatment with tetracycline was also performed. Immediate instillation of tetracycline after duct electrocoagulation produced only partial epithelial damage. The combination of duct electrocoagulation and delayed tetracycline instillation at 14 days produced complete destruction of all gallbladder epithelium and an effective chemical cholecystectomy. PMID- 1760694 TI - For debate: research in surgical training. PMID- 1760695 TI - Subtotal cholecystectomy. AB - Subtotal cholecystectomy has been carried out on 11 patients during a 5-year period, constituting 3.8 per cent of cholecystectomies performed during this time. The indications were severe inflammation/fibrosis in six patients, portal hypertension in three and the Mirizzi syndrome in two patients. There were no deaths and only minor in-hospital morbidity. One patient developed a common bile duct stone 21 months after the operation. None of the remaining patients has to date developed postcholecystectomy sequelae (mean follow-up period 29 (range 1 62) months). Subtotal cholecystectomy is a safe, straightforward and definitive operation in patients for whom standard cholecystectomy could be dangerous, and is a more attractive proposition than cholecystostomy. PMID- 1760696 TI - Effect of biliary infection on common bile duct healing in the rat. AB - It has been postulated that biliary infection plays a role in bile duct stricture formation. The aim of this study was to verify this hypothesis and to evaluate the effect of biliary infection on common bile duct healing. A 3-mm longitudinal choledochotomy was performed in 120 rats and closed with a continuous 11/0 Ethilon suture. Common bile duct division with end-to-end anastomosis using interrupted 11/0 Ethilon sutures was performed in another 30 rats. Biliary infection was achieved in half of the animals with retrograde injection of living 046:K1:H31 strain Escherichia coli recovered from the rat colonic content. All rats with choledochotomy, including those with biliary infection, showed no bile leakage at the suture line, and the bursting pressure at the site of choledochotomy exceeded 40 mmHg as early as 24 h. Rats with common bile duct anastomosis alone showed no stricture formation for up to 6 months after operation. All rats with biliary sepsis developed complete occlusion at the anastomosis. On scanning electron microscopy, the biliary epithelium was well preserved in all rats. The study suggests that in rats with biliary sepsis the risk of bile leakage after primary closure of the common bile duct is negligible, but biliary infection may play a critical role in common bile duct stricture formation. PMID- 1760697 TI - Treatment perspectives in locally advanced unresectable pancreatic cancer. AB - Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-fluorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at 1 year, two patients at 2, 3 and 4 years. A second-look operation was performed in four patients 6, 11, 12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer. PMID- 1760698 TI - Treatment of severe postvagotomy/postgastrectomy symptoms with the somatostatin analogue octreotide. AB - Fourteen patients with severe and persistent postvagotomy/postgastrectomy symptoms were entered into a trial of treatment with the somatostatin analogue octreotide, 50 micrograms twice daily 30 min before meals being self-administered by subcutaneous injection. Six of the seven patients completing the 3-month trial showed sustained overall improvement of symptoms. The remaining patients were unhelped by treatment or developed unwanted effects. Six of eight patients with dumping syndrome showed sustained improvement of dumping symptoms during treatment. Bile vomiting was relieved in three of four patients with this complaint. Diarrhoea accompanying dumping showed a variable response to treatment, with improvement in three patients and no change or worsening of this symptom in five. Two patients with severe postvagotomy diarrhoea alone showed no improvement. Four patients with unwanted effects and three patients who found no benefit stopped the trial medication early. Four further patients reported mild or transient side-effects. For patients with severe postvagotomy/postgastrectomy symptoms, a trial of octreotide seems justified when significant dumping symptoms are present and other treatment options have been exhausted. PMID- 1760699 TI - Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial. AB - A multicentre randomized prospective trial compared minimal surgery (under running the vessel or ulcer excision and adjuvant ranitidine) with conventional ulcer surgery (vagotomy and pyloroplasty or partial gastrectomy) for the treatment of bleeding peptic ulcer. This report is based on 137 patients (eight withdrawn through misdiagnosis or lost data), of whom 62 received conservative surgery and 67 conventional operation. Twenty-nine patients died, 16 (26 per cent) after conservative surgery and 13 (19 per cent) after conventional operations. The only significant difference between the groups was the incidence of fatal rebleeding, which occurred in six patients after conservative surgery compared with none after conventional surgery (P less than 0.02, Fisher's exact test). PMID- 1760700 TI - Transhiatal oesophagectomy for oesophageal carcinoma. AB - Between 1979 and 1990 transhiatal oesophagectomy and reconstruction with stomach was performed in 148 patients with carcinoma of the oesophagus. Ninety-seven patients were men and 51 were women; ages ranged from 21 to 88 years with a mean of 57.4 years. Dysphagia and weight loss were the usual clinical symptoms. The mean duration of symptoms was 14 weeks. Squamous cell carcinoma was present in 129 patients (87.2 per cent), 18 patients (12.2 per cent) had adenocarcinoma, and one had lymphoma (0.7 per cent). In two-thirds of the patients tumours were located in the middle thoracic (50 of 148 patients) or distal thoracic oesophagus (59 of 148 patients). Three-quarters of the patients had tumours determined as stage III. The mean length of hospital stay after operation was 12.8 days. Anastomotic leakage occurred in 15 cases (10.1 per cent). Pulmonary complications other than pneumothorax were observed in 36 cases (24.3 per cent). The 30-day postoperative mortality rate was 8.1 per cent (12 of 148 patients). Respiratory insufficiency was observed as the major cause of death (six of 12 patients). Mediastinitis due to necrosis of the transposed stomach in the mediastinum was the cause of death in three cases. Two-year actuarial survival rates in patients with cervical, upper, middle and lower thoracic tumours were 20, 22, 26 and 30 per cent respectively. Transhiatal oesophagectomy is safe and offers limited morbidity and mortality, although pulmonary complications and anastomotic leakage in the early postoperative period still pose a significant risk, especially for elderly patients in poor condition. PMID- 1760701 TI - Histopathological study of oesophageal mucosa in patients with varices: a comparison between bleeders and non-bleeders. AB - Thirty-six patients with oesophageal varices underwent a non-shunting operation including oesophageal transection. Of these, 16 had an emergency or elective operation (bleeders) and the remaining 20 had prophylactic surgery (non bleeders). A comparative study was performed between the bleeders and non bleeders in terms of preoperative endoscopic findings and histopathology of the oesophagus. The severity of red colour sign showed no significant difference between the two groups. The venous dilatation in each of the three layers of the oesophageal mucosa was demonstrated histologically to be of the same degree in bleeders and non-bleeders. In addition, the hepatic venous pressure gradient in cirrhotic patients did not differ between the two groups; for bleeders this was a mean(s.d.) of 15.2(6.1) mmHg and for non-bleeders 14.4(2.9) mmHg. We were unable to find any factors differentiating bleeders from non-bleeders, although these results do not justify prophylactic surgery for oesophageal varices. PMID- 1760702 TI - Staple-line erosion: a common source of recurrent bleeding following stapled oesophageal transection. AB - Recurrent bleeding after stapled oesophageal transection was studied in 73 patients with cirrhosis transected for acute variceal bleeding. The most frequent source of bleeding was partial or total circumferential oesophageal erosion at the transection: staple-line erosion. This lesion occurred in 36 (49 per cent) patients and was the source of rebleeding in 29 (40 per cent) patients with 54 episodes. Rebleeding in 22 (30 per cent) patients was due to varices in nine (12 per cent), peptic ulcer in six (8 per cent), gastric erosions in two (3 per cent) and unknown sources in five (7 per cent), accounting for 33 episodes. The mean(s.e.m.) blood transfusion requirement for bleeding from staple-line erosions were 1.5 (0.25) units per bleed versus other sources, 6.5(1.0) units per bleed (P less than 0.001). Staple-line erosion was present at the first postoperative endoscopy in 11 (15 per cent) patients but the time to appearance varied widely. The lesion was more common in patients with Pugh's grade A liver disease at the time of transection, reflecting the increased survival rate of these patients. Staple-line erosion is a common source of minor recurrent bleeding following stapled oesophageal transection. PMID- 1760703 TI - Perioperative blood transfusion does not promote recurrence and death after mastectomy for breast cancer. The Danish Breast Cancer Cooperative Group. AB - Several reports suggest that perioperative blood transfusion promotes recurrence and death after cancer surgery. We studied the effect of transfusion in 1599 patients who had mastectomy for carcinoma of the breast. In 228 transfused patients the disease recurred in 110 (48 per cent), compared with 647 (47 per cent) of 1371 non-transfused patients (P = 0.85). The 5-year recurrence-free survival rate was 0.54 in the transfused patients and 0.60 in the non-transfused group (P = 0.44). The transfused patients had a higher prevalence of risk factors than the non-transfused patients. Cox's multiple regression analysis confirmed that perioperative blood transfusion was of no importance. The study does not support the hypothesis that perioperative blood transfusion promotes recurrence after operation for breast cancer. PMID- 1760704 TI - Trauma audit: experience in north-east Scotland. AB - The management of 125 patients with trauma treated at Aberdeen Royal Infirmary from 1 January 1988 has been analysed using a microcomputer-based hospital trauma registry incorporating trauma and injury severity scores (TRISS) methodology. These patients fulfilled the North American Major Trauma Outcome Study (MTOS) inclusion criteria and were the first for whom data were available. Sixty-six patients had multiple injuries, of whom 52 were suffering from major trauma (defined as an injury severity score of 16 or greater). There were 14 deaths in the series, three (21 per cent) of which were considered to be preventable. Surgery was required in 84 (67.2 per cent) patients, of whom 59 (70 per cent) were operated on by a consultant or senior registrar. Five of six critically injured patients who died from their injuries were operated on by a consultant. PMID- 1760705 TI - Factors influencing local recurrence and survival in patients with soft tissue sarcoma of the upper limb. AB - Fifty-one patients with soft tissue sarcoma of the upper limb were studied to identify risk factors for local recurrence and survival. More than half (53 per cent) of the patients referred had locally recurrent disease. The flexor aspect of the forearm was the most common site of origin. The majority of patients were managed by a combination of conservative surgery and radical radiotherapy. Wide or radical excision was achieved in 49 per cent of cases. One-third of patients required partial resection of bone or neurovascular structures; 75 per cent of them had presented with local recurrence after treatment elsewhere. Skin grafts and flap repairs were used more often in patients with local recurrence (P = 0.013) and 20 (74 per cent) of those referred with locally recurrent disease have had no further local relapse. The overall 5-year survival rate of 80 per cent (95 per cent confidence interval 61-90 per cent) supports a policy of conservative surgery. Factors associated with a lower survival rate were deep fixation, origin in the flexor aspect of the forearm, and previous local recurrence. Deep fixation was also associated with an increased risk of local recurrence. Referral to a specialist unit at the time of initial presentation may result in lower rates of local recurrence and may improve the survival rate. PMID- 1760706 TI - Management of coeliac artery aneurysms. PMID- 1760707 TI - In situ femorodistal bypass: novel technique for angioscope-assisted intraluminal side-branch occlusion and valvulotomy. A preliminary report. AB - To allow and facilitate complete endoluminal vein preparation under angioscopic guidance for in situ femorodistal bypass grafting, a novel instrument was constructed. In experiments in cadavers we developed the occluder valvulotome, consisting of a modified Mills' valvulotome containing a laterally-ending working channel, a retrograde cutting blade and an advanceable Teflon tube within the working channel. Using this instrument in combination with commercially available wire coils, we successfully performed five femorocrural in situ reconstructions with endoluminal valvulotomy and embolization of a total of ten thigh tributaries. The technique allows angioscope-assisted valvulotomy and simultaneous endoluminal tributary occlusion, making long skin incisions and extensive vein dissection obsolete. PMID- 1760708 TI - Above-knee prosthetic grafts do not compromise the ipsilateral long saphenous vein. AB - Prosthetic graft materials are used preferentially by a number of surgeons for above-knee femoropopliteal bypasses. Using B-mode ultrasonography we have assessed the ipsilateral long saphenous vein in patients undergoing such bypasses to determine its suitability for future use in more distal bypasses. A total of 137 above-knee prosthetic grafts were performed over a 10-year period. Of the patients, 74 were available for further assessment. Overall, 97 per cent of veins were suitable for future bypass surgery if required. Above-knee prosthetic bypasses do not appear to jeopardize the ipsilateral long saphenous vein. PMID- 1760709 TI - Quantitative measure of small vessel anastomotic contour using corrosion resin cast models: an aid to surgical training. AB - A surgeon who had not previously carried out a small vessel anastomosis performed 20 consecutive anastomoses between human long saphenous vein and the left anterior descending artery of a pig's heart. Corrosion resin cast models were made of the anastomoses and subjected to a quantitative analysis of the anastomotic contour. A trend of improvement in contour parameters was found with increasing experience. This model may be useful for surgeons in training. PMID- 1760710 TI - Effect of weight on claudication distance. AB - Conservative measures to improve claudication distance include advice on smoking, exercise, diet and weight reduction. Although the effects of smoking, exercise and diet are established, the effect of weight is less clear. The aim of this study was to investigate the effect of carrying extra weight on the maximum walking distance in stable claudicants. Twenty stable claudicants were exercised on a treadmill (3.5 km/h, 0 degrees slope) carrying 0, 2.5, 5, 7.5 and 10 kg weights in randomized sequence. Maximum claudication distance and ankle: brachial pressure indices were recorded. Patients were categorized into mild or severe claudicants depending on their ability to walk 200 m. A response index (RI) was calculated as the reduction in claudication distance per kilogram load; RI = [CD0 CD10]/10 m/kg, where CD0 and CD10 represent claudication distance with 0 and 10 kg weights, respectively. Claudication distance was significantly reduced in subjects carrying 5 kg or more (P less than 0.01). A linear relationship was demonstrated between the mean claudication distance and the load carried (r = 0.98, P less than 0.01) with a mean response index of 10.2 m/kg. The mean(s.e.m.) RI in mild claudicants (25.9(9.5) m/kg) was greater than the value observed in the severe claudicants (3.3(0.8) m/kg; P less than 0.01, Mann-Whitney U test). This study demonstrates that weight adversely affects claudication distance and suggests that weight reduction may deserve greater emphasis in the management of some patients with intermittent claudication. PMID- 1760711 TI - Role of splenectomy as a salvage procedure in thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura is a rare but serious haematological disease for which first-line therapy is medical, but not always successful. The role of splenectomy in the management of such patients is unclear. This paper reports three patients with the condition who went into remission following splenectomy after other forms of therapy had failed. Because thrombotic thrombocytopenic purpura is nearly always fatal if a remission is not obtained, splenectomy should be considered in patients who prove to be resistant to medical therapy. PMID- 1760712 TI - Peripheral parenteral nutrition: effect of a standardized compounded mixture on infusion phlebitis. AB - The incidence and severity of infusion phlebitis was evaluated prospectively in 142 surgical patients who received peripheral parenteral nutrition (PPN) for a total of 700 days. In a first study phase 83 patients were given PPN for a total of 424 days. All nutrient solutions were delivered over a 12-h period from a 3 litre bag and the infusion sites rotated daily. These methods resulted in an incidence of phlebitis of 18 per cent, 75 per cent of the patients being fed successfully by PPN until resumption of oral nutrition. In an attempt to assess the importance of the method of delivering nutrient solutions, the next 59 patients were randomized to receive PPN as a compounded mixture or by a conventional technique with simultaneous infusion from separate bottles. Infusion phlebitis was significantly more frequent (P less than 0.001) in patients infused with separate bottles. There was no difference between the groups with regard to duration of nutrition or the need to establish central venous access. We conclude that PPN is a safe and cost-effective means of providing total parenteral nutrition in most surgical patients. The use of compounded mixtures significantly reduces the incidence of phlebitis without increasing total costs. PMID- 1760713 TI - Effects of different lipid emulsions on lymphocyte function during total parenteral nutrition. AB - A prospective randomized study of the immunological effects of three total parenteral nutrition (TPN) regimens in patients undergoing preoperative parenteral nutrition was conducted. In one regimen the calories were derived solely from glucose. The others were identical except that 50 per cent of the calories were provided as lipid emulsion, in one as long-chain triglycerides (LCT) only while the other contained half the fat as medium-chain triglycerides (MCT) and half as LCT (MCT/LCT). Natural killer (NK) activity and lymphokine activated killer (LAK) activity were significantly higher after TPN with the MCT/LCT solution. A significant fall in LAK activity occurred after TPN with the LCT solution. The interleukin 2 content in supernatants from activated T lymphocytes was significantly higher after TPN with the LCT-containing solution. Solutions containing LCT and those containing MCT perturb cytokine interactions, but this is less with MCT-containing solutions, which may augment certain responses. These observations may have implications for the design of TPN regimens. PMID- 1760714 TI - Surgical management of primary hyperhidrosis. PMID- 1760715 TI - Colon perforation during colonoscopy: surgical versus conservative management. PMID- 1760716 TI - Necrotizing fasciitis. PMID- 1760717 TI - Infrainguinal bypass surgery. PMID- 1760718 TI - Influence of obstructive jaundice on the serum levels of sodium. PMID- 1760719 TI - Sources of electrical transients in tectal neuropil of the frog, Rana pipiens. AB - We have studied the outer neuropil layers in frog tectum where the unmyelinated optic nerve fibers terminate. At any point in the neuropil an extracellular microelectrode records several different visually evoked electrical transients, distinct by size and shape. When classified by shape alone, each transient falls into one of 3 distinct classes. Some of these transients are binocularly driven, as originally described by Finch and Collett. The aggregate of the receptive fields of all the elements recorded at a single point defines a multiunit receptive field (MURF). Each MURF is characteristically oval, and divided into 3 sections along its long axis. Each section represents the aggregate of the receptive fields associated with one class of transient; i.e. transients belonging to only one specific class can be evoked by stimulating that part of the visual field corresponding to the appropriate section of the MURF. All of the MURFs mapped by recording in a single tectum are radially arranged in visual space about a central point, or 'visual pole'. Several conclusions are made. First, the two larger types of transient are generated postsynaptically by electrically active dendritic elements, specifically the beaded dendritic appendages of tectal neurons. The smallest type of transient is of presynaptic origin. Second, these tectal elements have a local and global anatomical order across the tectum, which accounts for both the tripartite structure of the MURFs and their radial arrangement about a visual pole. Third, since the large transients are of postsynaptic origin, genuine recordings of single retinal ganglion cell (RGC) activity can be made only in the optic nerve or retina itself. Fourth, information is conveyed over the unmyelinated optic nerve fibers at pulse rates as high as 80/s and is transsynaptically effective at such rates. Finally, the electrically active tectal dendritic elements, with their highly organized spatial arrangement, are an important component of the frog's visual processing apparatus, instead of being merely relays or repeaters. PMID- 1760720 TI - Phase-shifting effect of triazolam on the hamster's circadian rhythm of activity is not mediated by a change in body temperature. AB - Treatment with the short-acting benzodiazepine, triazolam (Tz), 6 h before activity onset (CT 6) induces large phase advances in the circadian rhythm of locomotor activity in golden hamsters free-running in constant lighting conditions. These phase shifts are associated with acute increases in locomotor activity. The acute increases in activity appear to be necessary for induction of phase shifts in the activity rhythm by Tz, since suppression of this activity by restraining the animal blocks the phase shifts normally induced by Tz. Furthermore, other stimuli which induce an acute increase in locomotor activity phase shift the circadian clock in a similar manner as does Tz. Since increased locomotor activity is associated with a rise in body temperature in mammals, and changes in temperature have been associated with changes in circadian rhythms, this study was designed to determine whether the phase-shifting effect of Tz on the circadian clock could be mediated by the change in body temperature resulting from the induced acute increase in locomotor activity. Hamsters free-running in constant light (LL) were implanted with Mini-Mitter biotelemetry devices and either injected with Tz at CT 6, injected with Tz at CT 6 and restrained for the next 6 h, or restrained for 6 h beginning at CT 6. Treatment with Tz resulted in large phase advances in the activity rhythm, while the other two treatments did not induce phase advances. Mean body temperature increased over control levels for all 3 groups during most of the 6 h following the beginning of treatment, and there were no significant differences in body temperature changes between any pairs of groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760721 TI - The influence of long-term potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain. AB - The influence of long-term potentiation (induced by repeated high-frequency stimulation of the perforant pathway) on the distribution pattern of astrocyte processes in the neuropil of the hippocampal dentate area containing the potentiated synapses was investigated by quantitative electronmicroscopy. It has been found that significant changes occurred in the ramification of astrocyte processes as well as in their topographic relation to synaptic complexes. When comparing the results obtained in LTP animals with active control or sham operated animals, we found significant higher numerical density, but smaller volume, higher surface density and closer apposition of astrocyte processes to the synaptic clefts, boutons terminaux or spines in the potentiated synapses containing neuropil. The glial reaction to synaptic activation has been seen most pronounced 8 h after the LTP induction. The results are pointing to a participation of the glia cells in the maintenance of the LTP effect as well as to a metabolic coupling between synaptic transmission and glia function for equilibrating the homeostasis by clearing the extracellular space next to the transmission zones. PMID- 1760722 TI - Expression of ALZ-50 immunoreactivity in the developing principal sensory nucleus of the trigeminal nerve: effect of transecting the infraorbital nerve. AB - Many neurons in the CNS die as a consequence of normal development. As these neurons die, they may be programmed to produce 'death proteins'. We explored the possibility that an antigen recognized by ALZ-50, a protein expressed in Alzheimer's-type neurofibrillary tangles, is generated during the process of neuronal death. The effects of transecting the infraorbital nerve on the expression of ALZ-50 immunoreactivity and neuronal death in the principal sensory nucleus of the trigeminal nerve (PSN) was examined. In normal rats, a small number of PSN neurons was ALZ-50-positive on postnatal day (P) 3. Transections on the day of birth (i.e. during the period of naturally occurring neuronal death) led to a 5-fold increase in the number of immunoreactive neurons expressing a 56 kDa protein on P3. In contrast, lesions on P25 (i.e. after the period of naturally occurring neuronal death) did not induce any neurons to exhibit ALZ-50 immunoreactivity. Thus, the 56-kDa protein recognized by ALZ-50 appears to be a death protein which is transiently expressed during the period of naturally occurring neuronal death. It is appealing to speculate that the pathological degeneration described in Alzheimer's brains results from the up-regulation of a quiescent developmental program. PMID- 1760723 TI - The effects of two 21-aminosteroids on overt infarct size 48 hours after middle cerebral artery occlusion in the rat. AB - The lipid peroxidation inhibitors U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4 pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9]-(11)-triene-3, 20-dione) and U74512E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16 alpha methylpregna- 1,4,9]-(11)-triene-3,20-dione) were tested for cerebroprotective properties in the rat. Focal cerebral ischemia was induced by irreversible occlusion of the middle cerebral artery (MCA-O). The 21-aminosteroids U74006F (1 mg/kg or 10 mg/kg, i.p.) and U75412E (1 mg/kg or 30 mg/kg, i.p.) were injected 30 min prior and 2, 6, and 24 h after MCA-O. The higher doses of U74006F or U75412E caused reductions in cortical infarct size ranging from 28 to 34%. The data suggest the 21-aminosteroids to be mildly effective after irreversible occlusion of the MCA but possibly to be more beneficial as part of a combined drug therapy in conjunction with Ca2+ or NMDA antagonists. PMID- 1760724 TI - The relationship between visual stimulation, behaviour and continuous release of protein in the substantia nigra. AB - In the substantia nigra, a protein (acetylcholinesterase) is secreted from the dendrites of dopaminergic pars compacta neurons, in a noncholinergic capacity. This non-classical phenomenon could be influenced by sensory stimulation: the effect of light flashing was investigated on the 'on-line' release of acetylcholinesterase and concomitant behaviour in the guinea-pig. The stimulus induced an increase in release of the protein and the appearance of chewing movements. Similarly, chewing could also be elicited by direct local application of exogenous acetylcholinesterase. The results suggest that visual stimulation causes release of AChE, which in turn facilitates movement. Therefore secretion of this protein within the substantia nigra might form an important intermediary step in visuo-motor interactions. PMID- 1760725 TI - Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats. AB - To determine whether hepatic encephalopathy may be associated with a disruption of circadian function, the circadian rhythms of locomotor activity and pineal melatonin content were examined in an animal model of complete portal-systemic shunting, rats with a portacaval anastomosis (PCA). The locomotor activity rhythm of all sham-operated animals entrained normally to a light/dark cycle and exhibited a normal free-running period during exposure to constant light. In contrast, PCA led to a dampening of the locomotor activity rhythm in all animals and the abolishment of a circadian periodicity in the activity rhythm of approximately 50% of rats during exposure to either a light/dark cycle or constant light. While normal diurnal variations of pineal melatonin content were seen in sham-operated rats, the amplitude of this variation appeared to be decreased in PCA animals. The similar effects of PCA on both a behavioral and an endocrine circadian rhythm, known to be regulated by a common neural pacemaker, coupled with studies indicating that a variety of other circadian rhythms may be disrupted in both animals and humans with hepatic dysfunction, suggests that this circadian disturbance originates within the pacemaker or on one of its afferent/efferent pathways. PMID- 1760726 TI - Effects of intra-amygdaloid injections of alpha-difluoromethylornithine and putrescine on the development of electrical kindling in rats. AB - In our previous study, an increase in concentration of putrescine was observed in the brain of amygdaloid kindled rats. To clarify the role of putrescine in kindling, the effects of intra-amygdaloid injections of alpha difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, or putrescine on the development of electrical kindling were examined in rats. Kindling stimulations were applied to the left amygdala. Pretreatment with DFMO (50 nmol) for 10 days by injection into the ipsilateral amygdala decreased both the number of stimulations and total afterdischarge (AD) duration required to reach first fully kindled state. Kindling-induced elevation of the putrescine concentration was inhibited by pretreatment with this dose of DFMO. On the other hand, pretreatment with putrescine (200 nmol) for 10 days into the same site of the brain retarded the behavioral and electrographic development of kindling seizure during the period of drug administration, although these treatments did not produce any changes in the number of stimulations or total AD duration. Putrescine (200 nmol) demonstrated no anticonvulsive effects in previously kindled animals. These results suggest that putrescine has an inhibitory effect on the development of amygdaloid kindling in rats. PMID- 1760727 TI - Taurine-like immunoreactivity in photoreceptor cells and mushroom bodies: a comparison of the chemical architecture of insect nervous systems. AB - Taurine is one of the most abundant amino acids found in the tissues of insect nervous systems. The distribution of taurine-like immunoreactivity was investigated in compound eyes, ocelli and mushroom bodies of Drosophila and Locusta. A comparison to the previously described taurine-like immunoreactivity in the brain of worker honeybees (J. Comp. Neurol., 268 (1988) 60-70) showed that the photoreceptor cells of all three insect species are immunoreactive. Immunoreactive mushroom body intrinsic Kenyon cells were also found in all three species. The intensity of the immunoreactivity was however graded, depending on the species. While the majority of Kenyon cells were stained in Apis and Drosophila, the immunoreactivity of the locust mushroom body was mainly confined to the intrinsic neurons originating in the accessory calyx. PMID- 1760728 TI - Extracellular space volume changes in the rat spinal cord produced by nerve stimulation and peripheral injury. AB - Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The alpha and lambda in L4 and L5 segments of unstimulated rats were alpha = 0.24 +/- 0.01 (i.e. ECS occupied 24 +/- 1% of the total spinal cord volume) and lambda = 1.54 +/- 0.04 (mean +/- S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration [( K+]e) and ECS volume in Rexed laminae III-V by 15.8 +/ 2.7% (n = 5). After the end of stimulation, when the [K+]e decreased below the original baseline (K+ undershoot), the ECS volume decreased by 20-45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2-10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15-40 min. The ECS volume decreased by 20-50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III-V, 5-10 min after injection of turpentine and 10-25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760729 TI - Microdialysis of extracellular noradrenaline in the hippocampus of the rat after long-term alcohol intake. AB - Intracerebral microdialysis combined with high-performance liquid chromatography and electrochemical detection was used to study the effect of chronic ethanol intake on the release of noradrenaline in the hippocampus of the awake, freely moving rat. The hippocampal sites were perfused with an artificial cerebrospinal fluid for 30 min at a rate of 2 microliter/min before ethanol intake and after one and 3 months of ethanol intake. The animals received a 10% ethanol solution as their drinking fluid. The basal release of noradrenaline before ethanol drinking varied from no measurable value to 28 pg in 50 microliters perfusate, possibly being dependent on the behavioral state of the animal. After one month of drinking the release had increased in 4 rats, was lower than before in two animals and remained unchanged in 3 rats. After 3 months of ethanol intake the release had increased in 7 rats out of the 9 and had remained unchanged in two. The mean amount of noradrenaline in 50 microliters perfusate after 3 months of drinking was 52 pg. Five rats out of 9 increased their ethanol consumption during the last two months. The results suggest that chronic ethanol intake affects the release of noradrenaline in the hippocampus, but that the effect is probably dependent on the duration of intake. PMID- 1760730 TI - Sensitization to noise-mediated induction of seizure susceptibility by MK-801 and phencyclidine. AB - The effect of single administrations of MK-801 (5-methyl-10,11-dihydro-5H dibenzo[a,d]cyclohepten-5,10-imine) or PCP (phencyclidine) on the induction of audiogenic seizure susceptibility by noise in immature rats was examined. Treatments with these non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists resulted in increases in noise exposure-dependent susceptibility. In neonatally drug-treated rats, seizures during adulthood were found to occur with significantly higher incidence and severity. Furthermore, drug treatments were found to lengthen what is normally a restricted developmental period within which susceptibility can be induced by noise exposure. The drugs, however, had no inherent ability to induce audiogenic seizure susceptibility if given alone. Moreover, in already-susceptible rats, MK-801 exhibited predictable anticonvulsant effects. These data suggest acute PCP or MK-801 exposures may transiently exacerbate risks inherent in certain forms of trauma. The mechanism underlying these effects is unknown although certain inferences are possible and may reveal much about epileptogenesis in this model. PMID- 1760731 TI - Behavioural evidence for a peripheral component in the enhanced antinociceptive effect of a low dose of systemic morphine in carrageenin-induced hyperalgesic rats. AB - This study reinvestigated the possible contribution of a peripheral action of systemic morphine in the modulation of the response to noxious pressure on inflamed paws, using a supraspinally integrated test and various low doses of naloxone. Rats received an injection of carrageenin into the right hindpaw which resulted in an ipsilateral inflammatory response and decreased threshold to noxious pressure. Four hours post-carrageenin, the injection of 1 mg/kg i.v. morphine induced a significantly enhanced antinociceptive effect on the inflamed compared to the non-inflamed paws. Intrapantar injection of extremely low doses of naloxone (0.5 and 1 micrograms in a volume of 0.1 ml) significantly reduced this effect (naloxone being more effective when administered at the same time as morphine, compared to 15 min later), while equal doses of naloxone given systemically were inactive. These data confirm that synergism of peripheral and central actions may result in the augmented analgesic potency of morphine in rats subjected to inflammatory conditions. In addition, they provide further evidence for the complexity of opioid actions in inflammatory processes. In particular, the results are in line with the hypothesis that the paradoxical antinociceptive effect of extremely low doses of i.v. naloxone described in several studies is due to a central action. PMID- 1760732 TI - A study of the hypothalamic pulse-generating mechanism responsible for LH release: electrical stimulation of the medial basal hypothalamus in the ovariectomized guinea pig. AB - In order to examine the neurophysiological properties of the hypothalamus responsible for the pulsatile release of luteinizing hormone (LH) the medial basal hypothalamus (MBH) of the ovariectomized adult female guinea pig was stimulated electrically through an implanted electrode and LH release was monitored as an indication of luteinizing hormone-releasing hormone (LHRH) release. Electrical stimulation (ES) consisting of monophasic square wave pulses with 0.5 ms pulse duration was applied for 2 min at 60, 40, 20, or 10 min intervals. Current intensity (80, 200, 500 microA) and frequency (8, 50, 100 Hz) were varied to determine the parameters of ES which resulted in an LH pulse with amplitude similar to that of a pulse induced by the endogenous pulse-generating mechanism. Blood samples were collected at 5 or 10 min intervals through an indwelling catheter, and LH was measured by RIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760733 TI - Prostaglandin E2 mediates the stimulatory effect of methoxamine on in vivo luteinizing hormone-releasing hormone (LH-RH) release in the ovariectomized female rhesus monkey. AB - Previously, we found that noradrenergic input through alpha 1-receptors modulates pulsatile release of luteinizing hormone-releasing hormone (LH-RH) in ovariectomized rhesus monkeys in the absence of estrogen. In the present study, the role of prostaglandin E2 (PGE2) in mediating alpha-adrenergic stimulation of LH-RH release is investigated. In the first experiment the effects of the alpha 1 adrenergic agonist methoxamine (MTX) on LH-RH and PGE2 release were examined. Push-pull perfusion of the stalk-median eminence (S-ME) was performed in conscious, ovariectomized monkeys, and perfusate samples were collected on ice. MTX (10(-5) M) was infused into the S-ME through the push cannula for 10 min at 90-min intervals, and LH-RH and PGE2 in aliquots of the same perfusate samples were measured by radioimmunoassay. Infusion of MTX significantly stimulated LH-RH release (n = 12; P less than 0.01) and PGE2 release (P less than 0.05). In the second experiment, the effect of PGE2 infusion on LH-RH release was tested. PGE2 (10(-7) M) was infused using the same protocol as above, and LH-RH was measured in the perfusates. Infusion of PGE2 through the push cannula significantly stimulated LH-RH release (n = 23; P less than 0.05). These results suggest that the stimulatory effect of MTX on LH-RH release is at least partly mediated by PGE2, since MTX stimulated not only LH-RH but also PGE2 release, and since PGE2 itself stimulated LH-RH release. Therefore, PGE2 may be an important endogenous mediator of alpha 1-adrenergic input stimulating pulsatile LH-RH release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760734 TI - Labeling of human retinohypothalamic tract with the carbocyanine dye, DiI. AB - The carbocyanine dye, DiI, was used to demonstrate human retinohypothalamic tract (RHT) projections in 6 normal human postmortem brains. In 5 of 6 brains, labeling was seen extending from the site of implantation in the distal optic nerve to both the ipsilateral and contralateral suprachiasmatic nuclei. This study confirms the presence of RHT projections in humans, and demonstrates the usefulness of DiI for neuronal tracing in human postmortem tissue. PMID- 1760735 TI - Dystrophic neurites infiltrate extracellular neurofibrillary tangles in Alzheimer disease. AB - The neurotrophic activity of beta-amyloid protein (beta-AP) has been suggested to be responsible for the dystrophic neurites that surround beta-AP deposits in senile plaques of Alzheimer disease. The recent finding that neurofibrillary tangles (NFT) that remain as remnants in the extracellular space (E-NFT) after the death of the neuron contain beta-AP, suggested that dystrophic neurites might also be associated with E-NFT. In this study, we use a probe for E-NFT, basic fibroblast growth factor (bFGF)-binding to show that E-NFT do contain dystrophic neurites. Since these neurites contain the amyloid precursor protein whose cleavage can lead to beta-AP, they may also play a role in further beta-AP deposition in the E-NFT. PMID- 1760736 TI - Suppression of 4-aminopyridine-induced paroxysmal depolarizing shift in rat amygdaloid neurons by diltiazem. AB - The effects of organic Ca2+ channel blocker, diltiazem, on the epileptiform activity induced by 4-aminopyridine (4-AP) were studied in rat amygdaloid slices using intracellular recording techniques. Application of 4-AP (0.5 mM) resulted in spontaneous and evoked epileptiform activity which consisted of an initial burst followed by a number of afterdischarges. The initial burst began with rapidly rising action potentials superimposed on a large depolarizing wave termed paroxysmal depolarizing shift (PDS). Diltiazem reversibly suppressed the amplitude and duration of PDS in a concentration-dependent manner. The IC50, estimated from the graph of the concentration-response relationship, was approximately 60 microM. These results demonstrate that a calcium current sensitive to diltiazem is involved in the generation of PDS and suggest that PDS is based on giant synaptic conductance as well as endogenous calcium currents. PMID- 1760737 TI - Nerve sprouting and endplate growth induced in normal muscle by contralateral partial denervation of rat plantaris. AB - The incidence of motor nerve and terminal sprouting was quantitatively analyzed in normal unoperated muscles, in homologous muscles contralateral to muscles which have been partially denervated, in partially denervated muscles, and in sham-operated muscles. Muscles were studied by light microscopy after staining motor endplates by a combined silver-cholinesterase stain. In addition, the incidence of endplates containing terminal sprouts, the number of terminal branch points per endplate, and endplate, and endplate size were also assessed in the various groups examined. We observed that following section of the L4 spinal nerve, the incidence of sprouting (preterminal and intranodal) in the contralateral muscle exhibited a 2-fold increase over sham-operated controls. We also found a correlation between nerve terminal sprouting, terminal branch point number and endplate size. All of these parameters were significantly increased in the contralateral muscles as compared to the sham-operated control muscles. These findings suggest that normal muscles undergo sprouting which can be enhanced by contralateral partial denervation. The possible underlying mechanism may be the transneuronal induction of sprouting. PMID- 1760738 TI - Trigeminal mediation of the diving response in the muskrat. AB - Stimulation of the nasal cavity elicits powerful cardiorespiratory responses similar to the diving response. In the present study, bradycardia and apnea were elicited in muskrats by stimulation of the nasal cavity with ammonia vapors. These responses could be blocked by injections of 2% lidocaine made bilaterally into the medullary dorsal horns of the trigeminal sensory complex. However, the bradycardia due to activation of the baroreceptor reflex with intravenous phenylephrine was retained. These data implicate trigeminal neurons in the medullary dorsal horn as modulators of autonomic activity, especially in the cardiorespiratory adjustments after nasal stimulation. PMID- 1760739 TI - Destruction of different fiber tracts underlies development of lateral hypothalamic lesion-induced hyperthermia and loss of bombesin-induced hypothermia. AB - The relative roles of lateral hypothalamic cell bodies and fibers of passage were assessed in the development of lesion-induced hyperthermia and bombesin-induced hypothermia. Electrolytic lesions or discrete fiber transections were combined with intracisternal bombesin injection to show that each of these two thermoregulatory effects involves fibers crossing the borders of the lateral hypothalamus; however, the two effects primarily involve fibers crossing different borders. Thus, the hyperthermia and the abolition of bombesin-induced hypothermia which follow lateral hypothalamic damage appear to result from disruption of separate thermoregulatory pathways. PMID- 1760740 TI - Axonal regeneration of retinal ganglion cells in the cat geniculocortical pathway. AB - The optic nerve of anesthetized cats was completely cut and the autologous sciatic nerve was transplanted. Sixty days later some populations of retinal ganglion cells were shown to regenerate the axon with retrograde HRP labeling. We verified that ganglion cells that had projected to the lateral geniculate nucleus (LGN) were able to regenerate through the transplant with a double-labeling method: diI was injected into the LGN prior to the transplantation, and dextran fluorescein was injected into the graft after axonal regeneration. Intracellular injection of HRP into regenerating ganglion cells in an in vitro preparation revealed that the two major cell types projecting to the LGN, alpha and beta, regenerated axons and showed normal dendritic morphology. PMID- 1760741 TI - The AT2 angiotensin receptor subtype predominates in the 18 day gestation fetal rat brain. AB - The angiotensin II receptor subtype-specific antagonists Dup 753 (AT1) and PD 123177 (AT2) were used to characterize the angiotensin II receptor subtypes present in 18 day gestation fetal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rat brain using in vitro receptor autoradiography. The AT2 subtype was predominant in the brain of both rat strains, even in areas that display predominantly the AT1 subtype in the adult rat brain. PMID- 1760742 TI - c-fos protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path. AB - The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c fos expression in both hippocampus and entorhinal cortex, and the increase of c fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy. PMID- 1760743 TI - Excitatory and inhibitory amino acid binding sites in human dentate nucleus. AB - Autoradiography of excitatory and inhibitory amino acid binding sites in human dentate nuclei indicated virtually no binding to N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acidB (GABAB) binding sites, and a low density of kainate binding sites. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, metabotropic-quisqualate, benzodiazepine, and gamma-aminobutyric acidA (GABAA) binding sites were present in moderate abundance. Our NMDA results differ from those found previously in rodents. GABAA receptors are probably the primary mediators of inhibitory neurotransmission and alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid and metabotropic-quisqualate receptors are probably the primary mediators of excitatory neurotransmission within the human deep cerebellar nuclei. PMID- 1760744 TI - Temperature dependence of carbachol-induced modulation of miniature end-plate potential frequency in rats. AB - In the rat soleus, the frequency of miniature end-plate potentials (MEPP) did not change after application of 10(-5) M of the cholinomimetic drug carbachol between 18 degrees C and 34 degrees C but decreased by 40% at physiological temperatures of 37-38 degrees C. The carbachol-induced decrease in MEPP frequency was not eliminated by 10(-7) to 10(-8) M atropine or 3 x 10(-7) (+)-tubocurarine similarly as had been previously found at frog neuromuscular junction. PMID- 1760745 TI - Transplantation of microencapsulated bovine chromaffin cells reduces lesion induced rotational asymmetry in rats. AB - Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue. PMID- 1760746 TI - The expression of proteins and activities of metabolic enzymes in transplanted brain tissue. AB - The middle three-fifths of the forebrains of 14-day-old embryos were obtained and transplanted into the cortical cavities of adult rats made 7 days prior to the transplantation. The expression of proteins, as revealed by 2-dimensional gel electrophoresis studies, and the activities of energy metabolizing enzymes in the mature allografts were compared with those in the 14-day-old embryonic forebrains and corresponding areas in the contralateral cerebral hemispheres of the hosts. They were shown to approach adult pattern and adult values after 10-12 weeks of growth. The biochemical findings were discussed and correlated with some of the anatomical observations. PMID- 1760747 TI - Evaluation of vagal afferent modulation of the digastric reflex in cats. AB - In the present study, we have examined the relative ability of cervical, thoracic, cardiac and diaphragmatic vagal stimulation to modulate the digastric reflex produced by tooth-pulp stimulation in anesthetized cats. The right maxillary tooth pulp was stimulated and the digastric reflex was recorded from the right digastric muscle. Cervical vagal stimulation produced a biphasic effect on the digastric reflex. The reflex was facilitated at conditioning test intervals less than 20 ms and inhibited at conditioning test intervals between 100 ms and 500 ms. Cardiac and thoracic vagal stimulation did not significantly facilitate the digastric reflex but inhibited the reflex at conditioning test intervals between 50 ms and 500 ms with maximum inhibition observed at 200 ms. In contrast, diaphragmatic vagal stimulation produced a weaker inhibition of the digastric reflex. The relative ability of different vagal segments to inhibit the digastric reflex was: thoracic = cardiac = cervical greater than diaphragmatic. The inhibitory effects were not related to cardiovascular responses to vagal afferent stimulation. These findings suggest cardiopulmonary vagal afferents represent an important source of vagal afferents which modulate the digastric reflex in the cat. PMID- 1760748 TI - Effects of acute and chronic ethanol treatment on pre- and postsynaptic responses to baclofen in rat hippocampus. AB - Interactions between the GABAB receptor and acute or chronic ethanol treatment were studied using extracellular and intracellular electrophysiological recording techniques. Bath application of the GABAB receptor agonist, (-)-baclofen (0.1-100 microM) induced concentration-dependent inhibition of extracellularly recorded dendritic excitatory postsynaptic potentials (EPSPs) in the CA1 region of hippocampal slices. Responses to baclofen were unchanged relative to control either by simultaneous application of ethanol (10-60 mM) or by previous chronic ethanol exposure. The membrane potential of CA1 pyramidal neurons was reversibly hyperpolarized an average of 5 mV by pressure ejection of baclofen (1 mM). Bath application of ethanol (30 mM) alone occasionally caused a small depolarization of resting membrane potentials in CA1 neurons but failed to increase hyperpolarizing responses to pressure-ejected baclofen. However, in slices from chronic ethanol-treated animals hyperpolarizing responses to bath-applied baclofen (10 microM) were reduced by approximately 30% relative to controls. These results suggest that GABAB-mediated responses in CA1 hippocampal pyramidal neurons are relatively resistant to the acute effects of ethanol, but that continuous exposure to ethanol sufficient to induce physical dependence may evoke an adaptive reduction in some GABAB receptor mediated responses. PMID- 1760749 TI - Exogenous tyrosine potentiates the methylphenidate-induced increase in extracellular dopamine in the nucleus accumbens: a microdialysis study. AB - Previous work has shown that the synthesis and release of dopamine may, under certain conditions, be influenced by an increase in the availability of its amino acid precursor, tyrosine. To examine whether exogenous tyrosine could potentiate the methylphenidate-induced increase in extracellular dopamine, male rats were implanted with microdialysis probes aimed at the right nucleus accumbens. Samples were collected from awake animals beginning 22 h after surgery. A repeated measures design was used involving the continuous collection of 20-min samples for a 4-h period once a day for 3 consecutive days. On a given day, an animal was infused with methylphenidate, tyrosine, or methylphenidate plus tyrosine. Periods of infusion with the active compounds were preceded and followed by baseline conditions, and treatments were counterbalanced to control for possible order effects. Methylphenidate plus tyrosine significantly increased extracellular levels of dopamine in comparison to drug alone. This effect was long-lasting, persisting into the post-treatment sampling period and peaking 40 min after the peak induced by methylphenidate alone. Tyrosine alone induced a small but significant increase in extracellular dopamine in the absence of any treatment to accelerate the firing of dopamine cells. These findings may have implications for the treatment of attention deficit hyperactivity disorder. PMID- 1760750 TI - [Control with progesterone of intracellular sulfate available in glandular epithelial cells of endometrium in culture]. AB - Sulfate incorporation was measured in subcultured glandular epithelial cells from guinea-pig endometrium, treated by estradiol alone or in concert with progesterone. Progesterone significantly increased sulfate incorporation in cellular and secreted macromolecules. However, the greatest effect of progesterone was on the size of the intracellular sulfate pool available for sulfation. This effect of progesterone was correlated with the percentage of cells exhibiting progesterone receptors in vitro. PMID- 1760751 TI - Stability of CD4/CD8 ratios in man: new correlation between CD4/CD8 profiles and iron overload in idiopathic haemochromatosis patients. AB - The proportions of CD4+, CD8+ cells were determined in peripheral blood samples obtained from 27 patients with idiopathic haemochromatosis and 67 healthy controls. Samples from the patients were obtained at the start of therapy and at intervals during intensive phlebotomy treatment in which 400 ml of blood are removed each week for 6 months to 2 years. Patients varied in their CD4/CD8 ratios from 0.8 to 4.2. An individual's CD4/CD8 ratio, however, remained unaffected by the repeated removal of large volumes of blood by phlebotomy confirming the existence of a homeostatic regulation of the relative numbers of the two major peripheral T cell pools in man. Follow-up of iron reentry into the transferrin pool at the end of the intensive phlebotomy treatment indicates that the relative proportion of circulating CD4/CD8 cells is critically related to the regulation of iron absorption. PMID- 1760752 TI - Ruminant pharmacology. AB - Aspects of drug disposition, metabolism, and toxicity in the ruminant animal are discussed, and illustrative examples are provided. The effects of the reticulo rumen on drug disposition in the ruminant are highlighted. PMID- 1760753 TI - Food animal practice. Applied pharmacology and therapeutics I. PMID- 1760754 TI - The impact of federal drug regulations on food animal practice. AB - This article discusses some of the regulations governing the use of drugs in ruminants. Because drug disposition is so influenced by dose, duration, and disease status, it is difficult to publish specific withdrawal time information. A discussion of calculation of withdrawal times is included. PMID- 1760755 TI - Problems and practice in mass medication of beef cattle. AB - Mass medication is a health management tool that, when used appropriately, results in cost savings and sound economic return to the food animal producer. Careful planning and consideration should precede the implementation of a mass treatment program, clearly defining the goal to be achieved and a detailed plan of execution. For economic as well as professional reasons, indiscriminate administration of antimicrobials to large groups of food animals should be avoided. PMID- 1760756 TI - Therapy of bovine bacterial pneumonia. AB - Practical strategies for developing rational therapeutic regimens based on in vitro sensitivity and pharmacokinetic disposition are presented. Special attention is given to Pasteurella haemolytica, which is regarded as the most frequent cause of bovine bacterial pneumonia. Bacterial-dependent and host dependent causes of therapeutic failure and potentially valuable novel therapies and drug combinations are considered. PMID- 1760757 TI - Clinical pharmacology of antimicrobial drugs for the treatment of septic neonatal calves. AB - For a given infection, each antibiotic will have a probability of producing a beneficial outcome. Decisions that increase the antibacterial activity of the therapeutic regimen against the bacterial infection will increase the probability of a beneficial outcome. Unfortunately, such decisions may increase the cost of therapy or the risks of toxicity. Finally, neonatal calves presented for therapy are not of uniform value. It is logical to employ different antimicrobial drugs and ancillary therapies when the value of the individual calf is considered. A constructive balance between efficacy, cost, and toxicity establishes the value of a therapeutic approach for the client. PMID- 1760758 TI - Treatment of diarrhea of neonatal calves. AB - Therapeutic strategies for the treatment of diarrhea of neonatal calves should be logical and should be targeted at correction of physiologic dysfunction. Appropriate, specific antimicrobial or antiprotozoal therapy should be instituted when colibacillosis, salmonellosis, or giardiasis is confirmed or suspected. All calves with diarrhea should be rehydrated if necessary, and proper nutritional support should be provided. Antisecretory agents such as flunixin meglumine and bismuth subsalicylate may be beneficial for treatment of calves with colibacillosis and salmonellosis. Adsorbants, such as attapulgite and bismuth subsalicylate, also may reduce loss of fluids. Perhaps loperamide or a similar drug will be proven effective in calves in the future. Potentially harmful drugs include several antimicrobial agents when they are administered orally, because they result in malabsorption; kaolin and pectin, which increase loss of ions during diarrhea; and motility modifiers that cause a decrease in all types of intestinal motor function. Finally, success should be measured by indicators of production such as survivability, days treated, weight gained, and net profit. Our goal should be to restore and maintain the health of the calf, not simply to alter the volume and consistency of the feces. PMID- 1760759 TI - Treatment of cardiovascular disease in cattle. AB - Cardiac diseases of cattle may involve valvular structures, myocardium, pericardium, or blood vessels and are manifested by the clinical signs of cardiac dysrhythmias, cardiac murmurs, generalized edema, muffled heart sounds, jugular venous distention, jugular venous pulsations, pulmonary edema, pleural effusion, or ascites. Digoxin, quinidine, and furosemide can be used effectively to control signs of CHF and cardiac arrhythmias. Combination antimicrobial therapy can be successful for cows with infective endocarditis and thrombophlebitis. Pericardial fluid drainage may temporarily improve cattle with traumatic pericarditis or lymphosarcoma so that short-term goals may be reached. PMID- 1760760 TI - Treatment of infectious arthritis and osteomyelitis. AB - Infectious arthritis and osteomyelitis are commonly encountered diseases of the skeletal system that can result in premature loss of an affected animal from the herd. Selection of the best possible treatment approach for an individual animal requires a solid understanding of the pathophysiologic processes involved in the infection of bone or joint; recognition of the unique aspects of the anatomy, physiology, behavior, management, and economics of the species involved; and a broad grasp of the availability and role of various therapeutic options. By recognizing the importance of all three of these areas, a clinician not only will be able to make realistic and effective judgments about care of commonly encountered cases today but also will have a sufficient basis for rational variations in therapy as pharmacologic options expand and environmental or economic pressures change. PMID- 1760761 TI - Ocular pharmacology. AB - Application of sound ocular therapeutic principle is more difficult in food animals than most other species. Financial or husbandry constraints limit the practitioner's ability to use the entire range of ocular drugs available or to use them with adequate frequency. These problems may be dealt with by using systemically administered drugs when effective or by employing vehicles or delivery techniques that necessitate minimal dosing frequency. By far the most important medically treatable eye disease encountered in food animal practice is IBK. Effective therapies include systemic administration of long-acting oxytetracycline, subconjunctival administration of a variety of antibiotics, or topical application of benzathine cloxacillin. Infectious conjunctivitis in sheep and goats due to a variety of agents may be treated successfully with tetracycline in most cases. Conjunctivitis and keratitis secondary to IBR virus usually are given supportive therapy only, although specific antiviral drugs have been used in the treatment of herpetic eye disease in other species. Anterior uveitis is best treated by corticosteroid and mydriatic therapy in addition to treatment of the underlying cause, if identified. PMID- 1760762 TI - Treatment of Mycobacterium paratuberculosis infection in ruminants. AB - Paratuberculosis is a chronic, debilitating, fatal condition that usually is clinically undetectable until the onset of copious diarrhea. Paratuberculosis is caused by an acid-fast organism, M. paratuberculosis. Successful eradication of paratuberculosis depends on the early detection of infected animals, thereby allowing removal of carrier animals from the herd. Treatment for paratuberculosis is therefore rarely indicated or undertaken; however, treatment may be considered for animals of exceptional genetic value or companion animals. Antimicrobials reviewed in this article for the treatment of paratuberculosis include isoniazid, rifampin, streptomycin, amikacin, clofazimine, and dapsone. Treatment of paratuberculosis requires daily medication for extended periods and results in palliation of the disease rather than a definitive cure. The treatment for paratuberculosis recommended by the authors is isoniazid at 20 mg/kg administered orally every 24 hours for the rest of the animal's life. When the animal has acute onset of diarrhea, rifampin at 20 mg/kg every 24 hours is also administered orally. In severe, imminently life-threatening cases, an aminoglycoside should be administered concurrently for 3 to 8 weeks. This protocol (isoniazid, rifampin, and an aminoglycoside) will help ensure that Mycobacteria organisms are sensitive to at least two of the antibiotics. Rifampin treatment can be discontinued if clinical signs of paratuberculosis disappear and the cost of therapy is judged excessive. The combined therapeutic approach has been used in three animals, and the results are presented in this article. Because isoniazid, rifampin, and some aminoglycosides are not approved for use in food animals in the United States of America, the meat or milk from treated animals should not be used for human consumption. PMID- 1760763 TI - Some ABC's of skeletal pathophysiology. 5. Microdamage physiology. PMID- 1760764 TI - Cyclosporin A: friend or foe? PMID- 1760765 TI - DEXA measurement of spine density in the lateral projection. I: Methodology. AB - Bone mineral content and bone mineral density (BMC in g and BMD in g/cm2) were measured using dual-energy X-ray absorptiometry (DEXA). DEXA scans in the lateral decubitus position required about 12 minutes for the L2-L4 sequence at 0.75 mA (dose 5 mrem) and 4 minutes at 4.75 mA (7 mrem). The former scans were done with the Lunar DPX densitometer and the latter with the Lunar DPX-L. One test of the algorithms used for measurement is the equality of BMC in both AP and lateral projections. BMC in the lateral projection averaged about 1% lower than in the AP projection in phantoms and for L2 + L3 in 8 subjects, but the difference was not significant. Additional tests were done on the effects of tissue thickness and position from the tabletop. There was little or no influence of tissue thickness from 18 to 30 cm on BMD results, but there was a small influence of thickness below 18 cm (0.01 g/cm2; P = 0.01) and of distance from the tabletop at extremes of positioning (0.02 g/cm2; P = 0.06). The precision in vivo was similar for both 4- and 12-minute scans; the standard deviation of repeat measurements was about 0.02 g/cm2, which was about 2% relative to the mean BMD for a region within the vertebral body. The latter region included half the BMC of the body, or 24% of the entire vertebra. Results of 4-minute scans on the DPX and 12-minute scans on the DPX-L in 9 subjects were highly correlated (r = 0.98; P less than 0.001). PMID- 1760766 TI - Calcium absorption in normal and osteoporotic postmenopausal women. AB - Hourly fractional absorption of radiocalcium (alpha), serum calcitriol, and a number of other variables were measured in 152 normal and 148 osteoporotic postmenopausal women. Alpha, body weight, and serum albumin were all significantly lower in the osteoporotic than in the normal women, and plasma alkaline phosphatase, fasting urinary calcium, sodium, and hydroxyproline were all significantly higher in the osteoporotic than in the normal group. The most significant determinant of alpha in each group was the serum calcitriol concentration, but calcium absorption relative to serum calcitriol was significantly lower in the osteoporotic than in the normal women. The serum calcitriol level was slightly but not significantly lower in the osteoporotic than in the normal group and accounted for only 20% of the difference in alpha between them. The implied "resistance" to calcitriol in the osteoporotic group was significantly related to serum albumin and body weight but independent of age. Urinary hydroxyproline was an inverse function of alpha and a positive function of fasting urinary calcium in the osteoporotic group. PMID- 1760767 TI - Isotopic exchange of ingested calcium between labeled sources. Evidence that ingested calcium does not form a common absorptive pool. AB - We studied the extent of salt dissociation during absorption of calcium from sources of differing absorbability by measuring fractional absorption from loads in the range of 200-300 mg in healthy adult women. Sources were labeled both intrinsically and extrinsically with 45Ca and 47Ca, respectively, and were fed alone and in combination with one another. We first confirmed our previous observation of superior absorbability of calcium oxalate over spinach calcium in a randomized cross-over design in 20 women. Spinach calcium exhibited only half the absorbability of the same load of calcium presented as the oxalate. Then, in 14 women fed spinach with both an intrinsic and an extrinsic label, apparent absorption of the extrinsic label averaged 0.130 +/- 0.041 and of the intrinsic label, 0.029 +/- 0.023. Thus, the extrinsic tag was partially, but not completely, bound by the spinach. In the same 14 women, milk absorption averaged 0.331 +/- 0.092 when ingested alone. However, when co-ingested with spinach, apparent milk calcium absorption fell to 0.267 +/- 0.079 and apparent spinach calcium absorption rose to 0.111 +/- 0.039. Thus, there was significant but incomplete label exchange between the two sources, indicating that at least some of the calcium from both sources enters a common preabsorptive, ionic pool. By contrast, we had previously shown no tracer exchange when labeled oxalate was co fed with labeled milk. We conclude that (1) the presence of calcium as the oxalate in spinach is not a sufficient explanation for the poor absorbability of spinach calcium; and (2) oxalate calcium and spinach calcium are absorbed by different mechanisms, one involving a common preabsorptive pool and the other not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760768 TI - Changes in apatite crystal size in bones of patients with osteogenesis imperfecta. AB - Apatite crystal size in compact bone of children (age less than 11 years) and adolescents (age greater than 12 years) with osteogenesis imperfecta (OI) was analyzed by X-ray diffraction. Eight type I, 4 type II, 11 type III, and 14 type IV OI patients were studied along with 9 controls. The crystal size was most significantly reduced in type II patients, all of whom had died at birth. Crystal size was also diminished in both children and adolescents with types III and IV, whereas with type I OI, crystal size was reduced in children only, returning to normal in adolescence. There was a trend toward increased bone crystal size with age in both OI patients and controls. PMID- 1760769 TI - Fourier transform infrared spectroscopic study of the carbonate ions in bone mineral during aging. AB - The environment of CO3(2-) ions in the bone mineral of chickens of different ages and in bone fractions of different density have been investigated by resolution enhanced Fourier Transform Infrared (FTIR) Spectroscopy. Three carbonate bands appear in the upsilon 2 CO3 domain at 878, 871, and 866 cm-1, which may be assigned to three different locations of the ion in the mineral: in monovalent anionic sites of the apatitic structure (878 cm-1), in trivalent anionic sites (871 cm-1), and in unstable location (866 cm-1) probably in perturbed regions of the crystals. The distribution of the carbonate ions among these locations was estimated by comparing the intensities of the corresponding FTIR spectral bands. The intensity ratio of the 878 and 871 cm-1 bands remains remarkably constant in whole bone as well as in the fractions obtained by density centrifugation. On the contrary, the intensity ratio of the 866 cm-1 to the 871 cm-1 band was found to vary directly and decreased with the age of the animal. In bone of the same age, the relative content of the unstable carbonate ion was found to be highest in the most abundant density centrifugation fraction. A resolution factor of the CO3(2-) band (CO3 RF) was calculated from the FTIR spectra which was shown to be very sensitive to the degree of crystallinity of the mineral. The crystallinity was found to improve rapidly with the age of the animal. The CO3 RF in the bone samples obtained by density centrifugation from bone of the same animal was found to be essentially constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760770 TI - A resolution-enhanced Fourier transform infrared spectroscopic study of the environment of the CO3(2-) ion in the mineral phase of enamel during its formation and maturation. AB - A resolution-enhanced Fourier Transform Infrared (FTIR) Spectroscopic study of the CO3(2-) ion in pig enamel of increasing age and maturity has demonstrated the existence of four different, main carbonate locations. The major CO3(2-) site arises as a result of the substitution of CO3(2-) ions in the positions occupied by PO4(3-) ions in the apatitic lattice. In addition, two minor locations have been identified in positions in which the CO3(2-) ions substitute for OH- ions. The fourth carbonate group appears to be in an unstable location. Its concentration has been found to decrease with aging and maturation, during which there is a progressive increase in the amount of mineral deposited in the enamel. The distribution of the carbonate ions in the different apatitic sites varies randomly during the formation of the mineral phase in enamel and during its maturation. Although these changes have been shown to be related to changes in the composition of the mineral phase, a comparison of the parameters assessing the degree of crystallinity of the mineral phase from upsilon 2CO3(2-) and upsilon 4PO4(3-) infrared absorption data reveals a significant discrepancy related to the nonhomogeneous partition of the CO3(2-) ion in the mineral phase. After maximum mineralization is reached, the composition of the mature mineral phase is decidedly different than that of the initial mineral deposited; the changes affect principally the concentrations of Ca2+, OH-, and HPO4(2-) ions, but not the CO3(2-) ions. PMID- 1760771 TI - Carbonate ions in apatites: infrared investigations in the upsilon 4 CO3 domain. AB - Fourier transform infrared (IR) spectroscopic investigations of precipitated carbonate apatites in the upsilon 4 CO3 domain reveal the existence of five bands at 757, 740, 718, 692, 670 cm-1 which can be assigned to several distinct environments of the carbonate ion in the apatite structure. In order to identify these environments precisely, fluoridated and pure type A carbonate apatites (i.e., with carbonate ions in monovalent anionic sites) were examined. The bands at 670 and 757 cm-1 were attributed to type A carbonate and their relative intensity was found to increase when the carbonate content of the apatite diminished or when samples were heated at 400 degrees C. Fluoridated apatites show only two bands, close to 718 and 692 cm-1, corresponding to type B carbonate ions (carbonate in trivalent anionic sites). The band at 740 cm-1 was revealed by heating the samples to 400 degrees C. This is due to OH ions' hydrogen bonded to fluoride and to carbonate ions in an undetermined apatite site. Despite the low intensity of IR bands, investigations in the upsilon 4 CO3 domain appear complementary to those in other carbonate vibrational domains and could be useful for a more precise identification of bone mineral. PMID- 1760772 TI - Effects of cyclosporine A on chick osteoclasts in vitro. AB - We have studied the effects of cyclosporine A (CsA) on basal and bovine parathyroid hormone (1-34) (bPTH)-stimulated bone resorption by osteoclasts in 24 hour cultures of chick long bone cells. At a high concentration (10 micrograms/ml), CsA had a cytotoxic effect on both osteoclasts and mononuclear cells in the culture. At 1 microgram/ml, CsA inhibited basal and bPTH-stimulated bone resorption but was not cytotoxic over 24 hours. We also studied the binding of bPTH to the osteoblastic cell line, Saos-2, and chick long bone cells in suspension culture. CsA inhibited bPTH binding in Saos-2 in a dose-dependent manner; inhibition of binding was also observed in chick bone cells. The effects of CsA on osteoclast viability and resorptive function may be due to a direct effect on the osteoclasts and/or to an interaction with the nonosteoclastic cell population in the culture. PMID- 1760773 TI - Clinical and laboratory parameters in adult diabetics with and without calcific shoulder periarthritis. AB - The clinical and laboratory parameters of calcific shoulder periarthritis (CSP) were examined in 900 patients with type II diabetes mellitus as well as in 350 age- and sex-matched control subjects. A threefold increased prevalence of CSP in diabetics compared with the control group was associated with the presence of longstanding and poorly controlled diabetes, hypercholesterolemia, and hypertriglyceridemia suggesting pronounced diabetic angiopathy, as well as with minor trauma and hypomagnesemia. Aging and serum calcium concentrations were not related to the presence of CSP. Thirty-two percent of diabetics with CSP were symptomatic; 15% of them presented with severe pain and restriction of shoulder movement. These findings confirm a close pathogenetic interrelation between CSP and diabetes mellitus. PMID- 1760775 TI - Experience with the novo DPA scanner. PMID- 1760774 TI - Correlations between photon absorption properties and failure load of the distal radius in vitro. AB - The bone mineral content (BMC) and cross-sectional properties of cadaveric radii were assessed by single photon absorptiometry (SPA). A new multiple-angle scanning technique was used in conjunction with SPA to measure the area and moments of inertia of the radial cross section in intact forearms. The radii of the same forearms were then broken in a failure test to simulate a fall on the outstretched arm. Colles' fracture was produced in 16 of 18 radii tested. The BMC divided by the bone width, which is called bone mineral density (BMD) in clinical applications, did not correlate with the load at failure in cadaveric forearms. The BMC alone did correlate significantly with failure load (r2 = 0.62), and the cross-sectional properties gave the best correlation with failure load in a sequential multiple regression (r2 = 0.80). We conclude that if SPA is to be used in clinical studies to predict risk of radial fracture or of fractures at remote skeletal sites, then BMC should be used rather than BMD. An even better indicator of radial bone strength than BMC would be a biomechanical parameter derived from the cross-sectional area and moments of inertia, which can be obtained from multiple-angle SPA. PMID- 1760776 TI - "60 minutes--a year later". PMID- 1760777 TI - Safety and tooth whiteners. PMID- 1760778 TI - Issues in the amalgam debate. AB - This paper reviews the facts available on the biological effects of mercury released from amalgam restorations in teeth. There seems to be no doubt that mercuric vapor is released from restorations, but we do not know how much of this mercury is deposited in human tissues. There is no scientific evidence to support the belief that vapors from dental restorations either cause or exacerbate human diseases. Therefore, there is no clinical justification at present for replacing amalgam with other less durable or less predictable restorative materials. PMID- 1760779 TI - Comparison of two popular methods for removal and killing of bacteria from dentures. AB - A study was undertaken to compare the efficacy of a soaking solution (Efferdent Extra-Strength Denture Cleanser Tablets) to mechanical cleaning with a denture paste (Advanced Formula Dentu-Creme Denture Cleaning Paste) to remove and kill plaque bacteria from removable dentures. The study was conducted in a randomized, four-way crossover fashion with 18 subjects. At each clinic visit, subjects were randomized to one of four treatment regimens: 1) no treatment; 2) brushing with denture paste; 3) soaking in Efferdent; 4) brushing followed by soaking in Efferdent. Microbiological sampling for plaque bacteria was made before and after each treatment. Aliquot samples of 10-fold serial dilutions were plated on supplemented Schaedler Agar (for total anaerobes) and on CVE agar (for fusobacteria). Analysis of covariance was performed on the log10 transformed scores at posttreatment using the pre-treatment scores as covariates. Significant treatment effects were: F(3,41) = 81.60, p less than 0.001 for anaerobes and F(3,50) = 104.38, p less than 0.001 for fusobacteria. Pairwise comparisons using Tukey hsd post hoc tests showed that for total anaerobes, treatments 1 and 2 yielded higher scores than treatments 3 and 4. For fusobacteria, treatment 1 greater than 2 greater than 3 or 4; no difference between treatments 3 and 4. The results demonstrated the superior performance of Efferdent over Dentu-Creme. PMID- 1760780 TI - A useful model for dental practice analysis, budgeting and income projection. AB - A versatile dental practice financial model, developed and utilized by the author, is presented. The model can be used by the dentist/manager to analyze dental practice financial data in order to identify practice inefficiencies and determine return on investment. It can also be used as a simple method of preparing a dental practice budget and projecting practice profit. Rationale for the model is explained and its use is discussed using hypothetical dental practice situations. PMID- 1760781 TI - Documenting nursing care in the operating room. PMID- 1760782 TI - Organ transplants and retrieval. PMID- 1760783 TI - The other side of caring. PMID- 1760784 TI - Ethical considerations of the extracorporeal membrane oxygenation procedure. PMID- 1760785 TI - Geriatric home health care. Conceptual and demographic considerations. AB - This article has explored conceptual and demographic aspects of HHC and the distinction between formal and informal care. HHC for elderly persons is shown to be mainly an informal, familial activity with important formal professional, skilled, and unskilled components. Formal home health care in the United States has undergone a historic transformation with the rise of third-party payment as a principal, defining force and with demographic and epidemiologic transition of the general population. Recent national studies demonstrate that the principal population group receiving HHC services--the chronically ill, functionally limited, noninstitutionalized elderly--is growing in number and as a proportion of the group with home and community service needs. Although diverse formal service innovations are being explored to meet these growing needs, current involvement of medical professionals in formal HHC emphasizes relatively short term, post-acute therapeutic and restorative care offered through Medicare certified home health agencies. PMID- 1760786 TI - Geriatric home care. PMID- 1760787 TI - The role of physicians in home health care. AB - Physician involvement in home care has declined markedly over the past 50 years. By contrast, the renaissance in home care in the US over the last decade has created a pressing need for greater physician participation and new roles for physicians as members of the home care team. This article reviews these developments and identifies the need for improved medical education and physician reimbursement if the desired physician involvement in home care is to become a reality. PMID- 1760788 TI - Geriatric assessment in the home. AB - Home assessment of health, environmental, and social factors, and their interactions that may impair the patient's functional capabilities and quality of life can play a critical role in the care of frail elderly patients. Home assessments can reveal important new health and social problems not identified in a clinical visit. Recent information suggests that home assessment is identified with good patient outcomes. Although this type of assessment is traditionally carried out by a nurse in the context of an interdisciplinary team, an individual primary care physician can also establish an ad hoc, multidisciplinary team to help care for frail elderly patients using principles derived from a comprehensive home assessment. PMID- 1760789 TI - Multidisciplinary home rehabilitation. A practical model. AB - The home is the most natural setting for rehabilitation. At home, the patient and family become active team members and the plan of care is created and carried out in the environment in which the patient will live. Home rehabilitation enhances the patient's autonomy, independence, and community reintegration. PMID- 1760790 TI - Home safety and fall prevention. AB - In conclusion, the majority, or at least a large proportion, of accidental injuries in the elderly are preventable with careful medical and environmental evaluation and intervention. A vigorous diagnostic, therapeutic, and preventive approach is appropriate in all older patients who fall in addition to those at a high risk of falling. Any intervention that can make inroads on this major cause of death and disability in the elderly population will clearly have major impact. PMID- 1760791 TI - Medication management in the home. AB - Medication management in home care patients differs from medication management in other settings. Medication choice among home care patients may be improved by a comprehensive geriatric assessment in the patient's home. Technological advances have improved the choices of drugs, routes of drug administration, and monitoring devices available at home. Other special aspects of medication management in the home include long-term ambulatory monitoring of complex drug regimens, the initiation of high-risk medication therapies, compliance aids for functionally impaired patients, and methods for an interdisciplinary team approach to health care. PMID- 1760792 TI - Home intravenous antibiotic therapy. AB - This article examines the development of a home intravenous program, types of outpatient intravenous programs, the criteria for patient selection, the equipment required, types of infections treated, the use of antimicrobics, clinical experience in the elderly, and financial considerations. PMID- 1760793 TI - Pain management at home. AB - The management of chronic pain should be a priority in geriatric home care. Pain is a common problem that has tremendous potential to influence the physical function and quality of life of elderly people during their remaining years. The experience of pain and its management at home are not analogous to institutional settings. Family and caregivers have important influences on pain management and may require education and support for the long-term management of chronic pain patients. Existing pain management strategies should be tailored to meet the special needs of geriatric patients and be sensitive to caregiver concerns. Implications, indications, and applications for high-tech pain management strategies need to be clarified for the management of older people at home. PMID- 1760794 TI - Home care for respiratory problems. AB - This article reviews current recommendations for the home care of geriatric patients with chronic pulmonary disease. Special attention is given to new bronchodilators, indications for home oxygen and ventilator use, as well as the use of nasal CPAP in elderly sleep apnea patients. The necessity of do not resuscitate (DNR) orders is also discussed. PMID- 1760795 TI - Managing the behavioral problems of dementia in the home. AB - The majority of persons with dementia are cared for in the home by family and friends. The goals of treatment in this setting are to maximize the quality of life of the demented person and minimize burdens on the caregiver. Behavioral problems are common with dementia and can lead to significant caregiver burden. Behaviors that are most common or most serious to caregivers include behaviors related to memory disturbances, restlessness and agitation, catastrophic reactions, day/night disturbances, delusions, wandering, and physical violence. A general method for clinicians to manage these problems involves the identification of the behavior and its antecedent and consequent events. Stressors that may cause behavioral problems include fatigue, a change of routine, excessive demands, overwhelming stimuli, and acute illness or pain. Caregivers can be taught to identify these stressors in order to prevent or alleviate troublesome behaviors. When behavioral techniques are not successful and the behaviors are particularly dangerous or burdensome, therapy with low doses of high-potency neuroleptics has been suggested. Measures such as these to help caregivers in the management of dementia at home can be instrumental in improving the quality of life for the person with dementia. PMID- 1760796 TI - Family dynamics and caregiver burden in home health care. AB - Planning an intervention involves the assessment of medical needs followed by an analysis of the family composition, dynamics, role allocations, coping mechanisms, mode of emotional expression, and the point in the family's developmental sequence. Therapeutic targets should be identified and prioritized. At that point, a behavioral probe or some specific recommendation that the family can easily follow should be made. A careful analysis of the response will indicate the ease with which more difficult change prescriptions can be introduced. Failure of the family to follow even the most simple suggestion may indicate that family therapy is needed. If the family is successful at carrying out the probe suggestion, however, the home health care team can proceed with greater confidence that their efforts will lead to improved patient care and healthy family functioning. PMID- 1760797 TI - Elder abuse. AB - Elder abuse encompasses physical, psychological, and financial abuse and also includes the violation of an individual's rights, or social abuse. Detection of elder abuse is often obstructed by the denial or shame of the abused older adult and the denial or improper assessment by health care professionals. The ethical struggle professionals face when they suspect abuse may also impede assessment or intervention. Preliminary data on etiologic factors related to elder abuse suggest that misinformation, the caregiver's lack of understanding of the needs of older adults, social isolation, a history of dysfunctional family relationships, and the psychopathologic factors of the caregiver are salient factors for understanding elder abuse. In addition, caregiver burden related to the care of the impaired elder and other external life events is a risk factor for elder abuse. Self-neglect is the type of elder abuse most often reported and the most difficult to handle, because older adults have a right to refuse services. Home care providers often face practical and ethical dilemmas in cases of self-neglect. When making an assessment for elder abuse, it is best to use a multidisciplinary approach. In addition to physical indicators (bruises, malnutrition, fractures), attention must be paid to the social, family, and sexual history of the patient. The psychological history of the patient and caregiver is also important. Reporting laws exist in all states, and health care practitioners must become familiar with the laws in their states. Awareness of elder abuse by professionals working in home care is essential, because the failure to detect abuse can interfere with interventions and in some cases lead to death. PMID- 1760798 TI - Quality assurance in home care. AB - The current increasing role of home care in US health care has brought with it the need for the development of standards addressing the quality of home care services. Home care poses quality assessment difficulties because of the broad spectrum of in-home procedures and services now available. Home care professionals (including physicians), as well as local, state, and national medical organizations all play a significant role in developing and enforcing quality assurance standards in home care. PMID- 1760799 TI - Cost-effectiveness of home care. AB - Home health care is uniformly accepted by patients, caregivers, health professionals, policymakers, and the public as a desirable way to provide care to disabled individuals and the frail elderly. Given the lack of positive impact of home care upon functional status, cost, and nursing home use, as well as documented additional cost, future research must focus upon positive aspects from past experiences. Careful targeting of patients most likely to benefit from this care has produced better results. Satisfaction with care has been shown consistently. Managed home health care may have the potential, especially the impact of physician involvement with team care on hospital use, to contain costs. The intuitive belief that home care is beneficial and a worthwhile expense, held by policymakers and health care professionals alike, needs to be fully researched by studies that carefully examine the wide spectrum of home care benefits for disabled or chronically ill individuals in relation to varying cost levels that the population and health care system can absorb. The challenge is here, and those who believe in home care need to make use of the results of these previous, rather nonsupportive studies. Additional research is needed to measure the impact of active physician participation in the team care provision of home care services and the impact of managed home care on the cost of hospital care in the population most at risk for recurrent hospitalization. This same research must document not only more effective targeting of individuals, but also the maintenance of increased satisfaction with care--strongest motive for the need to prove the cost-effectiveness of home care. PMID- 1760800 TI - African-American men. Perceptual determinants of early cancer detection and cancer risk reduction. AB - Research has shown that African-American men have a higher incidence, a higher death rate, and a lower survival rate for most cancers. But currently there are few studies addressing factors influencing the health care trends of this high risk population. A study focused on identifying factors that contribute to early cancer detection and cancer risk-reduction health behavior in African-American men was therefore implemented. There is evidence to support the conclusion that perceptions do significantly contribute to the health behavior of African American men. Those having the greatest impact were related to methods of early cancer screening. Clearly, if the National Cancer Institute's goal to reduce the mortality from cancer in the general population by 50% from the base rate in 1984 is to be met by the year 2000, there must be an increase in programs targeting African-American men. Every day African-American men can take steps to help protect themselves from cancer. Our charge as health care clinicians, educators, and researchers is to pinpoint ways to encourage them to do so. PMID- 1760801 TI - Clinical decision making and pain. AB - Pain management is intimately linked to decision making. Nurses play a key role in making decisions regarding pain and its management. This paper presents data from a preliminary study (N = 53) extending the investigators' pain research into the areas of clinical decision making and ethical dilemmas related to pain management. Nurses completed surveys focused on actual experiences of caring for patients in pain. The results identify common clinical decisions related to pain, barriers to providing optimum pain relief, and ethical/professional conflicts in pain management. Decisions related to the amount of pain intensity, when to give medications, and choice of analgesics. Nurses identified verbal and nonverbal cues central to their decisions regarding pain assessment. Barriers to effective pain management included physician knowledge and cooperation, patient/family knowledge and cooperation, as well as nursing knowledge and time. Respondents identified ethical dilemmas about overmedication or undermedication, conflicts with physicians or patients, and concern over opioid side effects. A tentative model of decision making related to pain is presented. PMID- 1760802 TI - Systematic pain records and their impact on pain control. A pilot study. AB - This study examined the impact of a systematic nursing pain assessment tool (PAT) and pain flow sheet (PFS) on pain management. A control group (N = 23) was compared with a treatment group (N = 20) of hospitalized patients on a medical oncology unit. In the control group, "routine" charting of pain was done in the nurses' narrative notes. Patients in the treatment group underwent standardized pain assessment and documentation using a PAT and PFS. The treatment group reported significantly lower average pain intensity ratings (chi 2 = 5.019, p = 0.02) on day three of follow-up. In addition, a greater number of patients in the treatment group (85%) reported decreased pain intensity from day one to day three as compared with the control group (57%). This study supports other research and recommendations in the literature that use of systematic pain records can improve pain management. PMID- 1760803 TI - A survey of nursing students' knowledge of cancer pain control. AB - The World Health Organization estimates that approximately 3.5 million people suffer daily from cancer pain. Recently, a Midwestern state was named by the World Health Organization to lead worldwide efforts in controlling the pain experienced by cancer patients. As part of this effort, the Nursing Education Committee conducted a statewide study of first year and final year nursing students from 19 nursing programs. The purpose of this study was to determine nursing students' perceptions and knowledge about cancer pain control. After the deans and directors of the nursing programs were contacted to obtain their agreement to participate, questionnaires composed of 26 items were mailed to each nursing school and distributed to students. Nine hundred thirty-eight questionnaires were returned to the researchers, realizing a 40% return rate. Data analysis reflects poor knowledge about the prevalence of cancer pain and its management. Using the student's t-test, significant differences between the scores of first year and last year students were found with last year students achieving higher mean scores. It was concluded that more information about how to manage cancer pain needs to be provided in nursing curricula. It is recommended that faculty members frequently update their knowledge and skills about cancer pain management. PMID- 1760804 TI - Process of dying. Defining characteristics. AB - Health professionals should not be forcing the terminal patient into preestablished stages, but rather should take into account the actual experiences of the individual. The purpose of this study was to identify the defining characteristics of the dying process within the terminal phase. A retrospective audit of 11 deceased clients' charts from a hospice program was conducted. Each client had been diagnosed with terminal cancer. Defining characteristics of the process of dying were delineated and organized into groups of subjective and objective phenomena. These included anorexia, absence of pain, nausea, vomiting, tachycardia, respiratory status, withdrawal of self, secretions, mental status, urinary output, restlessness, bowel sounds, blood pressure, internal temperature, skin temperature, skin color, edema, and diaphoresis. Although the sample size was small, these findings confirmed that the dying process for terminal cancer patients was an individualized experience. Additional research is needed to build on this framework. PMID- 1760805 TI - Determinants of anticipatory nausea and anticipatory vomiting in adults receiving cancer chemotherapy. AB - There is a need for further empirical investigation of variables that may contribute to the occurrence of anticipatory nausea and/or anticipatory vomiting (AN/AV) in persons receiving cancer chemotherapy. The purpose of this study was to examine the relationship of AN/AV in adults receiving an initial course of cancer chemotherapy in an outpatient setting with the following set of variables: symptom distress, mood disturbance, stage of disease, sensitivity to conditioning cues, emetic potential of antineoplastic drugs, age, psychosocial stress, and ability to cope. Thirty-two percent of the sample developed anticipatory nausea. Multivariate statistics were used to examine the contribution of the variables to the prediction of AN/AV. Analysis of the data revealed that 53% of the variance accounted for was contributed by the following combination of variables: emetic potential of drug, level of symptom distress, mood disturbance, stress and ability to cope (p = .001). The total percentage of cases correctly classified was 88.3%. This combination of variables correctly classified 100% of patients who experienced anticipatory nausea (n = 15). Eighty-two percent of patients who did not experience anticipatory nausea and/or anticipatory vomiting (n = 28) were classified correctly. PMID- 1760807 TI - Effect of a glucan, sizofiran, on natural-killer activity of 5-fluorouracil treated murine bone marrow cells. AB - The number of bone marrow cells in C3H/He mice was reduced 3-4 days after treatment with 130 mg/kg intraperitoneal 5-fluorouracil (5-FU). Higher rates of spontaneous proliferation and natural killer (NK) activity, accompanied by an increase in asialoGM1-positive cells, were observed in treated mice. When sizofiran at a dose of 200 micrograms/animal was intramuscularly injected after 5 FU treatment, the rates of proliferation and NK activity of bone marrow cells were higher than with 5-FU alone. The cell number was not influenced by sizofiran alone. These results indicate that all precursors of the various mature cell types (including NK cells) differentiate and regenerate rapidly to replace cells damaged by 5-FU treatment, and that sizofiran has the potential to assist this recovery. These results suggest that administration of sizofiran after chemotherapy may be useful in cancer patients. PMID- 1760806 TI - T cell targeting in cancer therapy. AB - Targeting of immune cells by bispecific antibodies has proven a powerful tool for the investigation of cellular cytotoxicity, lymphocyte activation and induction of cytokine production, as well as to represent an innovative form of immunotherapy for the treatment of cancer. The hallmark of this approach is the use of the specificity of monoclonal antibodies to join target and immune cells by virtue of the dual specificity of bispecific antibodies for the two entities. More precisely the bispecific antibody has two different binding sites, which are capable of recognizing tumor associated antigens on the one hand and lymphocyte activation sites on the other. This process of crosslinking results in the activation of the lymphocyte and triggering of its lytic machinery, as well as lymphokine production. A major advantage of this therapeutic modality is, that use is made of the normal cellular immune defence system and therefore is only associated with minor toxicity. The distinct lymphocyte populations, which can be used for adoptive immunotherapy and the various bispecific antibody preparations, as well as the chimeric immunoglobulin/T cell receptor construction are the major topics of this review. PMID- 1760808 TI - Human lymphokine-activated killer (LAK) cells: III. Effect of L-phenylalanine methyl ester on LAK cell activation from human peripheral blood mononuclear cells: possible protease involvement of monocytes, natural killer cells and LAK cells. AB - We have shown that depletion of monocytes from human peripheral blood mononuclear cells (PBMC) by L-phenylalanine methyl ester (PheOMe) enhanced lymphokine activated killer cell (LAK) generation by recombinant interleukin-2 (rIL-2) at high cell density. In this study, we have investigated the mechanism of action of PheOMe on LAK activation by using trypsin, chymotrypsin, tosylphenylalaninechloromethanol (TPCK, a chymotrypsin inhibitor), tosyl-L lysinechloromethane (TLCK, a trypsin inhibitor), phenylalaninol (PheOH), and benzamidine. PBMC were treated with 1-5 mM PheOMe for 40 min at room temperature in combination with the various agents, washed and assessed for their effects on natural killer (NK) activity against K562 cells and monocyte depletion. The treated cells were then cultured with or without rIL-2 for 3 days. LAK cytotoxicity was assayed against 51Cr-labeled K562 and Raji tumor target cells. TPCK at 10 micrograms/ml partially inhibited depletion of monocytes by PheOMe. TLCK did not prevent depletion of monocytes nor inhibition of NK activity induced by PheOMe. TPCK and TLCK inhibited NK activity by themselves. TPCK but not TLCK inhibited rIL-2 induction of LAK cells. On the other hand, PheOH and benzamidine (analogs of PheOMe) lacked any effect on monocyte depletion but abrogated the inhibitory effect of PheOMe on NK activity. They had no effect on rIL-2 activation of LAK activity enhanced by PheOMe. Trypsin potentiated the inhibitory effect of PheOMe on NK activity and monocyte depletion. Trypsin partially inhibited IL-2 activation of LAK activity enhanced by PheOMe. Chymotrypsin had little effect on NK activity but prevented the inhibitory effect of PheOMe on NK activity. It had little effect on monocyte depletion induced by PheOMe. PheOMe was hydrolysed by monocytes and chymotrypsin to Phe and methanol as determined by HPLC. TPCK inhibited hydrolysis of PheOMe by monocytes. Our data suggest that the effects of PheOMe on monocytes, NK cells and LAK activation involve protease activities of monocytes. PMID- 1760809 TI - Characterization of a monoclonal antibody directed against the epidermal growth factor receptor binding site. AB - In this work a new monoclonal antibody (mAb), designated MGR1, which recognizes the epidermal growth factor receptor (EGF-R) binding site, is described. The main characteristic of this mAb is its ability to discriminate between cells that express normal levels of EGF-R from cells with overexpression, the detectability threshold by immunocytochemical tests being 5 x 10(4) receptors/cell of 10 microns diameter. MGR1 was found to inhibit EGF binding on the relevant target cells, and vice versa its binding was inhibited by EGF, which indicated that MGR1 recognizes the EGF receptor binding site. MGR1 exerted an inhibitory effect on both the in vitro and in vivo growth of cells with EGF-R overexpression, but had no effect on cells with a normal expression of the receptor. Tumour growth inhibition in athymic mice was also obtained on already implanted tumours. MGR1 therefore seems to be an adequate reagent for the development of immunotherapeutical approaches suitable for the treatment of tumours with EGF-R overexpression. PMID- 1760810 TI - Immunotherapy of B lymphoma by anti-idiotype antibodies: characterization of variant tumour cells appearing a long time after the initial tumour inoculation. AB - Immunotherapy of a murine B-cell lymphoma by antibodies to idiotypic determinants of its IgM, resulted in surviving tumour-free mice. Several of these mice, however, did develop tumours a long time after the initial inoculation of the tumour cells, or upon rechallenge of the survivors with B-lymphoma cells. The presence of tumour cells during this long latent period may have been due to the development in the host of an anti-idiotype immune response. These late developing tumours were detected by a radioimmunoassay and characterized by immunofluorescent staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis. Cells of some late-developing tumours lost the idiotype recognized by the antibodies used for the immunotherapy. Several of these tumours expressed IgM on the cell surface, while others did not, because of the absence of light chains. They were identical in the structure of their rearranged mu chain genes proving their derivation from the original inoculation. Cell lines obtained from the late-developing tumours differed in their tumorigenicity. The appearance of idiotype-negative tumour cells as a result of anti-idiotype immunotherapy has a great impact in our efforts to cure lymphoma by this modality. PMID- 1760811 TI - Production of tumor necrosis factor alpha and interferon gamma in interleukin-2 treated melanoma patients: correlation with clinical toxicity. AB - Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). We measured the serum levels of TNF alpha and IFN gamma in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 x 10(6) IU or 12 x 10(6) IU Cetus IL-2/m2 by i.v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNF alpha and IFN gamma levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFN gamma levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNF alpha production, however, were not predictable and did not correlate with either IFN gamma or toxicity. Some patients had modest increases in TNF alpha production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNF alpha in IL-2 cancer patients, which do not correlate well with toxicity. PMID- 1760812 TI - Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours. AB - A long-term-cultured cytotoxic T lymphocyte (CTL) line (E/88) was obtained from splenic lymphocytes of BALB/c (H-2d) mice bearing the weakly immunogenic colonic carcinoma C26. This line was shown to be alpha/beta TCR + V beta 6 + CD3 + CD8 + CD4- and to recognize a common tumour-associated antigen on syngeneic carcinomas and sarcomas in a major-histocompatibility--complex-restricted and T-cell receptor(TCR)-mediated fashion. The assessment of cytotoxic activity on a panel of 30 normal and neoplastic target cells of differing etiology and histo-type showed that E/88 CTL lysed syngeneic colon carcinomas and some fibrosarcomas but not leukemias, lymphomas or mammary carcinomas. Clones derived from the E/88 line exhibited the same lytic pattern. Moreover, anti-T3, anti-Lyt2.2, anti-alpha/beta TCR and anti-V beta 6 mAbs as well as anti-H-2d antisera abolished cytotoxicity when used in blocking experiments. The therapeutic activity of E/88 CTL upon in vivo transfer was assessed in mice bearing either experimental or spontaneous metastases of C26. In both models therapy with E/88 lymphocytes in combination or not with interleukin-2 was highly effective. Adoptive immunotherapy carried out with two clones obtained from line E/88 showed comparable therapeutic effects. In addition, treatment of syngeneic mice bearing experimental metastases of in vitro E/88-lysable or E/88-resistant tumours, showed that E/88 CTL can eradicate metastases of the former but not of the latter neoplasms. These data indicate that long-term CTL lines recognizing common tumour-associated antigens can be derived from tumour-bearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors. PMID- 1760813 TI - Tumour rejection after adoptive transfer of line-10-immune spleen cells is mediated by two T cell subpopulations. AB - The growth of line-10 tumours in naive guinea pigs is prevented by adoptive transfer of spleen cells that are hyperimmune to this hepatocellular carcinoma. To study the T cell subpopulations responsible for the adoptive transfer of immunity, various cell populations were removed from immune spleen cells using monoclonal antibodies (mAbs) and magnetic microspheres. Spleen cell subpopulations were identified by mAb after flow cytometry and rosette formation with the magnetic microspheres. mAb CT5 was confirmed to be a pan T cell marker, while the CT6 (anti-T-suppressor/cytotoxic) and CT7 (anti-T-cell) markers were present on two different T cell subpopulations. So our results show that CT7 mAb cannot be used as a pan T cell marker as was published previously. Moreover, the mAb H155 (anti-T-helper/inducer) reacted with the same T cell subpopulation recognized by CT7. So we designated this H155/CT7-positive subpopulation as T helper/inducer cells. Removal of the CT6-, CT7-, or the H155-positive T cells from the immune spleen cells resulted in loss of the in vitro proliferative response to line-10 tumour protein and tuberculin purified protein derivative (PPD). The H155/CT7 (anti-T-helper/inducer)-positive spleen cells did not express MHC class II antigens as determined by mAb 25E3. In most experiments, elimination of MHC-class-II-positive cells did not change the in vitro proliferative response to line-10 protein, whereas the response to tuberculin PPD was completely abrogated. Immune spleen cells after depletion of CT6-, CT7- or H155-positive cells, failed to transfer immunity. However, after depletion of MHC-class-II antigen-positive cells the line-10 immunity was still present, whereas the immune response to tuberculin PPD was lost. In conclusion, our data indicate that immunity to the line-10 tumour is the result of a cooperation between at least two different T cell subpopulations, the T helper/inducer (CT7/H155) cells and the T suppressor/cytotoxic cells (CT6). If this is a common feature, then the therapeutic approach of in vitro expanded TIL cells should take into consideration the requirement of two T cell subsets. PMID- 1760814 TI - Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma. AB - The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05). PMID- 1760815 TI - Biochemical and immunological responses of hairy cell leukemia patients to interferon beta. AB - Ten hairy-cell leukemia patients were treated with interferon beta (IFN-beta) at a dose rate of 2 x 10(6) IU/m2 x 5 days for 4 weeks (induction therapy) and, thereafter, at the same dose three times a week for 11 months (maintenance therapy). The effect of this treatment on serum neopterin, beta 2-microglobulin, (2'-5')oligoadenylate [(2'-5')An] levels, intracellular (2'-5')An values and human Mx protein synthesis was analysed. There were significant rises in serum neopterin and (2'-5')An levels during both induction and maintenance, whereas beta 2-microglobulin levels rose only during induction. Rises in intracellular (2'-5')An were documented mainly during induction, but they were not significantly higher than pretherapy values. IFN beta provoked an increase in human Mx protein synthesis over the entire induction-maintenance period, but was only significantly higher than baseline during induction. All markers proved useful for monitoring the effects of IFN beta dose schedules, but were not predictive of clinical outcome. Natural killer activity and IFN gamma production, which were initially defective, followed a different trend from that of the other factors studied, in that increases were documented only late in the course of therapy when the disease was already in remission. PMID- 1760816 TI - Production of interleukin-1 and tumour necrosis factor in non-Hodgkin's lymphoma patients. AB - Peripheral blood monocytes from non-Hodgkin's lymphoma (NHL) patients were assessed for the monocyte functions with respect to their ability to secrete interleukin-1 and tumour necrosis factor (TNF) and their cytotoxic potential to tumour target WEHI 164 clone 13. Our results indicate comparable levels of interleukin-1 and TNF production by NHL patients. The cytotoxic potential by monocytes was also not depressed in these patients. The data obtained suggest normal monocyte functions in NHL patients. PMID- 1760817 TI - Potentiation of T cell immunity against radiation-leukemia-virus-induced lymphoma by polysaccharide K. AB - C57BL mice inoculated with radiation leukemia virus (RadLV) develop preleukemic cells long before the onset of leukemia. These cells are potentially immunogenic but fail to elicit an immune response in the host because of the appearance of virus-specific suppressor T cells. We have studied the effect of polysaccharide K (PSK) on the generation of RadLV-specific cell-mediated immune responses in vitro. Long-term exposure to PSK in culture potentiated the ability of immunized T cells to respond to a RadLV-induced lymphoma. It also abrogated the suppressive activity of suppressor T cells and simultaneously boosted the ability of reactive T cells to respond. The dual immunostimulating activity of PSK resulted in the generation of T cytotoxic lymphocytes that could lyse lymphoma cells in vitro. The results suggest that PSK could be used as a prophylactic immune response modifier in preleukemia. PMID- 1760818 TI - An overview of radioimmunotherapy. AB - In reviewing the current state of affairs in radioimmunotherapy the paper focuses on the main difficulties thus far encountered and the procedures designed to avoid or circumvent these problems. The long range beta-emitters 90Y and 188Re have replaced 131I as the isotopes currently receiving most attention for use in radioimmunotherapy, and a range of new chelators are under investigation for in vivo stability and immunogenicity. Approaches aimed at improving tumour targetting and antigen expression such as two-step pretargetting techniques, tumour necrosis treatment and cytokine pretreatment are summarized. Methods designed to improve host-Mab interactions are outlined and the need to incorporate successful ideas from current cancer therapies is emphasised. PMID- 1760819 TI - Importance in timing of cyclophosphamide on the enhancement of interleukin-2 induced cytolysis. AB - We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL 2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days -10 and -15 followed by IL-2 (50,000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day -10 or -15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoGM1, prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration. PMID- 1760820 TI - Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers. AB - We have previously shown that thymocytes from low-dose melphalan (L-phenylalanine mustard)-treated MOPC-315-tumor-bearing mice (melphalan TuB) are able to generate an enhanced level of anti-MOPC-315 cytotoxicity, as compared to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated or low-dose melphalan-treated normal mice, upon in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL 2). Here we show that the generation of enhanced anti-MOPC-315 cytotoxicity by melphalan TuB thymocytes depends on the ability of the thymocytes to proliferate. In addition, the ability of melphalan TuB thymocytes to generate an enhanced level of anti-MOPC-315 cytotoxicity correlated with their ability to proliferate more readily than thymocytes from untreated tumor-bearing mice and thymocytes from untreated or melphalan-treated normal mice in response to stimulation with MOPC-315 tumor cells plus a low concentration of rIL-2. Moreover, although fresh melphalan TuB thymocytes do not contain a higher percentage of phenotypically mature cells (i.e., CD4-/CD8+ or CD4+/CD8-) than do thymocytes from normal mice or untreated tumor-bearing mice, after a 5-day culture with both MOPC-315 tumor cells and a low concentration of rIL-2, cultures of thymocytes from melphalan TuB contained a much higher percentage of CD4-/CD8+ (but not CD4+/CD8-) cells than did cultures of thymocytes from the other two sources. Since CD4-/CD8+ cells were previously shown to be responsible for the exertion of antitumor cytotoxicity by thymocytes stimulated with MOPC-315 in vitro, our results indicate that the enhanced antitumor cytotoxicity exerted by melphalan TuB thymocytes following in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of rIL-2 is due, at least in part, to an expansion of the pool of CD4-/CD8+ effector cells. PMID- 1760822 TI - International experience with nitrates. PMID- 1760821 TI - Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen. AB - Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse. PMID- 1760823 TI - Evaluation of the antianginal and anti-ischemic efficacy of slow-release isosorbide-5-mononitrate capsules, bupranolol and their combination, in patients with chronic stable angina pectoris. AB - The effects of slow-release isosorbide-5-mononitrate (IS-5-MN), 25 mg once daily, bupranolol, 50 mg once daily, and their combination on exercise-induced ST segment depression at comparable work load, maximal work load, exercise capacity, frequency of anginal episodes and sublingual nitroglycerin consumption were studied in 30 patients with chronic stable angina pectoris. The patients were assigned in a randomized, double blind protocol, to either form of monotherapy, for 12 days, and thereafter to combined therapy for 12 days. Exercise stress test was performed before treatment and at 2 and 16 h after drug administration on the first and 12th day of each treatment period. ST-depression at comparative work load at 2 h after dosing was reduced by 49% acutely after administration of IS-5 MN. This effect was not significantly altered after 12 days of treatment and during combined therapy. In those patients treated by bupranolol alone, an effect was observed only after 12 days - a 24% reduction in ST depression. At the 12th day of combined therapy ST-segment depression was reduced by 65%. At 16 h after dosing there was no significant reduction in mean values of ST-segment depression in either groups, but some patients in each group showed a sustained effect for 16 h. Both drugs increased maximal work load and exercise capacity at 2 h after administration. This effect was sustained in the IS-5-MN group also at 16 h after administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760824 TI - Isosorbide-5-mononitrate and atenolol in the treatment of stable exertional angina. AB - Fourteen men and six women, 48-68 years old, with stable angina and effort induced ST-segment depression (ST-D) were treated with isosorbide-5-mononitrate (IS-5-MN) 2 x 40 mg/day and/or atenolol (AT) 100 mg/day in a double-blind randomized sequence during two 6-week periods. The patients performed ergometer tests. AT caused more decrease of heart rate at rest and at comparable work-load than IS-5-MN. Blood pressure at rest was in the normal range. Decrease of blood pressure at rest and at effort was similar with both agents. Combined administration of the two drugs was not more effective than monotherapy with AT or IS-5-MN in lowering heart rate and blood pressure. The average ST-D at comparable effort was for placebo 2.3 mm, for IS-5-MN after 2, 4, and 6 weeks, 3, 6, and 12 h, respectively, after medication, 1.4, 1.0, and 1.3 mm, and for AT 1.2, 1.4, and 1.4 mm, respectively. Administration of the drugs together caused additional highly significant reduction of ST-D (0.3-0.9 mm). The results indicate that IS-5-MN and AT have a similar beneficial effect on effort-induced myocardial ischemia, which is enhanced by their combined administration. The drugs alone and in combination are effective for as long as 12 h after administration of IS-5-MN, and 24 h after administration of AT. Moderate signs of tolerance to IS-5-MN were found after 6 weeks of therapy. PMID- 1760825 TI - Nitrates for myocardial salvage in the 1990s. AB - Low-dose intravenous nitroglycerin infusion for the first 48 h is becoming routine in the management of acute myocardial infarction in North America. It is most widely used as primary therapy in patients admitted more than 6 h after acute infarction. Such therapy has been shown to limit infarct size, infarct complications and remodeling. However, it is being applied increasingly more as an adjunct before, during and after thrombolytic therapy. Several trials are underway to test the effectiveness of more prolonged therapy, with early intravenous nitroglycerin followed by buccal or oral formulations for several weeks, in further limitation of ventricular remodeling, dilatation, aneurysm formation and in preserving function. Nitrates may prove to be a useful adjunct or alternative to angiotensin-converting-enzyme (ACE) inhibitors for long-term therapy. PMID- 1760826 TI - Evaluation of the antianginal effect of isosorbide-5-mononitrate in patients with chronic stable angina pectoris. AB - The antianginal and anti-ischemic properties of isosorbide-5-mononitrate (ISMN) were evaluated in 40 patients with chronic stable angina pectoris in a randomized double-blind parallel-group placebo-controlled study. After 2 weeks' placebo run in period the patients were randomized to either ISMN, orally 20 mg 2-3 times daily (titrated) or placebo. They underwent bicycle exercise stress test at the end of the placebo period and after 4 weeks of treatment. Compared with placebo ISMN increased the exercise performance, reduced ST-segment depression, anginal frequency and sublingual nitroglycerin consumption. All these changes were statistically significant. It may be concluded that ISMN is an effective antianginal and anti-ischemic agent in patients with chronic stable angina pectoris. PMID- 1760827 TI - Randomized double-blind comparison of the effects of isosorbide dinitrate retard, verapamil sustained-release, and their combination on myocardial ischemic episodes. AB - The antianginal and anti-ischemic efficacy of isosorbide dinitrate (ISDN) retard 120, verapamil 120 sustained-release (s.r.) and their combination was evaluated in 30 patients with chronic angina pectoris. The study was a randomized, double blind crossover comparison. The evaluation was determined by exercise testing and 24-hour electrocardiographic ambulatory monitoring. The sum of ST-segment depression at comparable exercise levels was reduced by 37% (p less than 0.001) after verapamil 120 s.r. and by 45% (p less than 0.001) after combination therapy. After ISDN retard 120 the sum of ST-segment depression was also slightly reduced by 18% without attaining statistical significance. Total walking time and time to angina pectoris during treadmill exercise were significantly prolonged after all treatments. The sum of ST-segment depression in the 24-hour Holter ECG was reduced by 46% (p less than 0.001) after verapamil and by 39% (p less than 0.01) after combined therapy. After ISDN retard 120 the mean reduction was 34% (p less than 0.01). In conclusion, the result of the study indicated that ISDN retard 120, verapamil 120 s.r. and a combination of both drugs are effective in reducing the frequency and duration of ischemic episodes in patients with ischemic heart disease. PMID- 1760828 TI - Treatment of angina pectoris with isosorbide-5-mononitrate. A multicenter study in general practice. AB - In this multicenter study 191 practitioners treated 532 patients with coronary artery disease and chronic stable angina pectoris by isosorbide-5-mononitrate (IS 5-MN), 20 mg 2-3 times daily. At the end of this period the frequency of anginal attacks was reduced by 83% and nitroglycerin consumption by 85.7% (p less than 0.0001). 40.1% of the patients categorized this treatment as very good, 28.6% as excellent and 23% as good. Serious adverse effects were observed in 2% of the patients and 6.4% of the patients discontinued treatment during the study because of inefficacy, infarction, death, or adverse effects. At the end of the study 90.2% of the patients were still on IS-5-MN. In conclusion, IS-5-MN is an effective treatment for patients with chronic stable angina pectoris. It is well tolerated, with minimal side effects. PMID- 1760829 TI - Evaluation of effectiveness and tolerability of isosorbide mononitrate during a three-year period in patients with angina pectoris. AB - The antianginal effect and tolerability of isosorbide mononitrate (ISMN), 20 mg 2 3 times daily, orally were investigated in an open study in 28 patients, suffering from coronary heart disease and stable angina pectoris. Ergometric exercise tests were carried out before treatment and 2 h after drug intake, every 3 months during the first year and at 6-month intervals during the following 2 years. At the conclusion of the 3-year study the reduction of ST-segment depression, which had amounted to 58% after 1 year, could be improved to 78% (p less than 0.01). The frequency of angina was markedly reduced during the treatment with ISMN. While 14 of the patients had more than 3 episodes per day prior to the study, 16 patients were symptom-free at the end of the three years' therapy, and none of the patients had more than 1 or 2 attacks per day. The consumption of sublingual nitroglycerin diminished by 94% after one year and by 98% after 3 years of therapy (p less than 0.01). Headache was the only adverse effect observed in some of the patients (at the initiation of the treatment only). In conclusion this study demonstrated (1) the good tolerability of ISMN, at the doses used, and (2) the fact that the antianginal efficacy may be enhanced during the course of the therapy. PMID- 1760830 TI - Nitrate therapy in heart failure. AB - Nitrates are drugs of first choice in patients with acute heart failure. Acute pulmonary edema can be successfully treated with single or repeated doses of sublingual nitroglycerin. In cases of prolonged acute heart failure, e.g. in the setting of acute myocardial infarction, nitroglycerin or isosorbide dinitrate can be given by the intravenous route for up to 24 h. Patients with acute myocardial infarction usually benefit from nitrate therapy if filling pressures are high and/or left ventricular function is compromised. Nitrate therapy can be considered safe if arterial blood pressure is maintained above 95 mm Hg. With these precautions nitrates can reduce infarct size and the incidence of complications as well as improve long-term prognosis. In the chronic treatment concern has risen with regard to possible nitrate tolerance. Thus, therapy schedules allowing for nitrate-poor phases are generally recommended. Therapy schedules with constant-rate delivery of drugs achieved with patches or intravenous administration of nitrates should be used with caution. PMID- 1760831 TI - Sustained-release IS-5-MN in the treatment of coronary heart disease. AB - In a double-blind, randomized cross-over study the antianginal efficacy and tolerability of Elantan Long (50 mg sustained-release IS-5-MN) were compared with a 80-mg sustained-release (s.r.) IS-5-MN formulation. 28 patients were enrolled in the study, which consisted of a 3-day washout period on placebo, an active treatment of 14 days (cross-over after 7 days) and a final 3-day withdrawal period on placebo. Ergometric exercise tests with simultaneous ECG monitoring were carried out 2 and 10 h post administration (p.a.) on the last days of each period. Under 50 mg s.r. IS-5-MN the mean ST- segment depression under comparable load was reduced by 67% 2 h p.a. and by 70% 10 h p.a. The reduction under the 80 mg IS-5-MN form was about 76% 2 h p.a. and 78% 10 h p.a. Maximum workload, working capacity, duration of exercise, time to angina pectoris and time to ST segment depression greater than 0.1 mV were markedly increased under therapy with each dosage. Comparisons between the medications revealed significant differences only in time to ST-segment depression greater than 0.1 mV and in ST-segment depression under maximum workload at 10 h p.a. which were increased more by the higher dosage. The incidence of anginal attacks decreased by almost 80% in the patients under both treatments. Ten patients under each dosage were completely freed from attacks. Adverse drug reactions occurred in 14 patients, 10 times under 80 mg s.r. IS-5-MN, 5 times under Elantan Long and twice under placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760832 TI - Hemodynamic effects of transdermal nitroglycerin patches in patients with acute myocardial infarction. AB - Transdermal nitroglycerin patches are used mainly in the therapy of angina pectoris. However, the magnitude and duration of their effects are still controversial. In this study, transdermal discs with nitroglycerin were given to 14 patients with acute myocardial infarction (AMI) and mild hemodynamic impairment. Seven patients received Nitroderm TTS, and seven patients Deponit 5 (in this case 2 patches), the nitroglycerin dose being 10 mg. Hemodynamic measurements were made 19-24 h after application of the patch and 1 h after its removal. Comparing with the values obtained 1 h after removal of the patch, 19-24 h after the application of the patch heart rate was significantly higher (90.2 +/ 3.8 vs. 85.6 +/- 4.0 min-1; p less than 0.01), mean right atrial pressure was significantly lower (10.8 +/- 1.0 vs. 12.7 +/- 1.3 mm Hg; p less than 0.01), and so were the pulmonary artery pressure: systolic (36.9 +/- 3.0 vs. 43.0 +/- 3.1 mm Hg; p less than 0.001), mean (26.8 +/- 2.1 vs. 31.4 +/- 2.0 mm Hg; p less than 0.001) and the capillary wedge pressure (19.2 +/- 1.8 vs. 23.0 +/- 1.9 mm Hg; p less than 0.01). These findings revealed that in patients with AMI hemodynamic effects persist for at least 19 h after single application of a nitroglycerin patch of 10 mg. The therapy is safe and the risk of side effects is small. PMID- 1760833 TI - Comparative evaluation of intravenous isosorbide dinitrate and nitroglycerin in patients with acute myocardial infarction. AB - The efficacy of isosorbide dinitrate (ISDN) and nitroglycerin was studied in 115 patients with acute transmural myocardial infarction admitted to the Coronary Care Unit not later than 12 h after the onset of chest pain: 58 patients not later than 2 h after the onset of chest pain, 49 after 3-6 h and 8 patients in the period of 6-9 h. There were 69 men and 45 women, mean age 62.4 +/- 0.9 years. The duration of the preceding clinically evident coronary artery disease was in 12 patients 1 year, in 29 2-3, in 22 4-5 and in 16 patients 6 years or more. In 36 cases the chest pain of acute infarction was the first presentation of coronary artery disease. Thirty-seven patients had a previous myocardial infarction. Fifty patients had concomitant systemic hypertension. The patients were divided into 3 groups depending on the type of therapy received: group I, receiving anticoagulants only, served as control; patients of groups II and III received, in addition to the anticoagulants, intravenous ISDN or nitroglycerin, respectively. The patients were monitored for recurrent chest pain, electrocardiographic changes, clinical parameters and cardiac enzyme changes. ISDN, at a dose of 10 mg/h over the first 3 days of infarction, had marked antianginal effect, limited the dimensions of the necrotic area, reduced the number of ischemic relapses and the development of heart failure. Compared to nitroglycerin, ISDN exerted a more prolonged action (up to 12 h), did not affect heart rate and blood pressure, and had a marked antiarrhythmic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760834 TI - Hemodynamic mechanisms of the effect of nitroglycerin in patients with acute myocardial infarction. AB - We studied the hemodynamic response to intravenous nitroglycerin (NTG) in 40 patients with and without acute heart failure (hemodynamic subsets I-IV) during acute myocardial infarction. Hemodynamic measurements were performed by right heart catheterization. The results showed that NTG response influenced mainly the preload and to a lesser extent the afterload, however these changes were dependent on initial hemodynamic status. The changes in mean arterial pressure and cardiac index were predominantly related to pretreatment pulmonary wedge pressure and slightly to systemic vascular resistance. Response to NTG could be predicted with 85% probability as a decrease of pulmonary wedge pressure, with 58% probability as a decrease in mean arterial pressure and cardiac index, and with 32% probability as an increase in cardiac index and a decrease in systemic vascular resistance. These results indicate that NTG therapy could have optimal results in patients with elevated pulmonary wedge pressure and normal cardiac index, while in the subsets with low mean arterial pressure or low cardiac index potentially deleterious decrease in these values could occur. Therefore the optimal condition for use of intravenous nitroglycerin in the patients with acute heart failure is isolated pulmonary congestion. PMID- 1760835 TI - Slow release isosorbide-5-mononitrate therapy in angina pectoris. Effects of exercise performance and hemodynamics. AB - The possibility of maintaining preload reduction and enhancement of exercise tolerance during an interval treatment with 100 mg/day of slow-release isosorbide 5-mononitrate (IS-5-MN) was investigated in 12 patients (aged 57 +/- 5.0 years) with angiographically confirmed coronary artery disease and chronic stable angina pectoris. The effects of a single dose (acute test) were compared with those following an 8-day (chronic) regimen of mononitrate administration. Two hours after administration of 100 mg sustained-release IS-5-MN, mean resting pulmonary artery pressure (PAP), measured with a Swan-Ganz catheter, was reduced by 32% (p less than 0.001) and at submaximal exercise level (50 W, 3 min) by 37% (p less than 0.001). At individually highest comparable work loads mean PAP was reduced by 37% (p less than 0.001), and at maximal work load the PAP reduction was 14% (p less than 0.05). At the end of 1 week of therapy with sustained-release IS-5-MN a slight, clinically irrelevant reduction of hemodynamic effect was recorded. Work capacity increased after 1 h by 79% (264 +/- 154 vs. 472 +/- 180 W x min, p less than 0.01), still significantly above base-line 10 h after nitrate administration. No difference from baseline was demonstrable 24 h after medication. During interval therapy the improved work capacity was fully maintained (chronic, 1 h: 280 +/- 119 vs. 532 +/- 160 W x min, p less than 0.001). There was no significant difference between the plasma IS-5-MN levels at acute and chronic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1760836 TI - Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. PMID- 1760837 TI - Similarity between the DNA-binding domains of IHF protein and TFIID protein. PMID- 1760838 TI - Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. AB - Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox. PMID- 1760839 TI - B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. AB - A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer. PMID- 1760840 TI - Maturation of the immune response in germinal centers. AB - Germinal centers develop in peripheral lymphatic tissue during the primary immune response and may play a crucial role in affinity maturation. We have compared the diversification of the antigen-specific repertoire of B cells, both from within and from outside the germinal centers, during the murine response to 2 phenyloxazolone (phOx). By sequencing V kappa Ox1 L-chains characteristic of phOx specific antibodies, we show that somatic mutations accumulate in germinal center B cells and that a mutation conferring high affinity binding is found with increasing frequency. An analysis of V/D/J rearrangements suggests that this mutation occurred independently in many B cells, which were then preferentially expanded. We conclude that, although the hypermutation mechanism may be activated before germinal centers develop, affinity maturation by hypermutation and selection takes place in the germinal centers. PMID- 1760841 TI - Molecular basis of symbiotic host specificity in Rhizobium meliloti: nodH and nodPQ genes encode the sulfation of lipo-oligosaccharide signals. AB - The symbiosis between Rhizobium and legumes is highly specific. For example, R. meliloti elicits the formation of root nodules on alfalfa and not on vetch. We recently reported that R. meliloti nodulation (nod) genes determine the production of acylated and sulfated glucosamine oligosaccharide signals. We now show that the biochemical function of the major host-range genes, nodH and nodPQ, is to specify the 6-O-sulfation of the reducing terminal glucosamine. Purified Nod factors (sulfated or not) from nodH+ or nodH- strains exhibited the same plant specificity in a variety of bioassays (root hair deformations, nodulation, changes in root morphology) as the bacterial cells from which they were purified. These results provide strong evidence that the molecular mechanism by which the nodH and nodPQ genes mediate host specificity is by determining the sulfation of the extracellular Nod signals. PMID- 1760842 TI - Induction in the developing compound eye of Drosophila: multiple mechanisms restrict R7 induction to a single retinal precursor cell. AB - The development of the Drosophila R7 photoreceptor cell is determined by a specific inductive interaction between the R8 photoreceptor cell and a single neighboring precursor cell. This process is mediated by bride of sevenless (boss), a cell-surface bound ligand, and the sevenless (sev) tyrosine kinase receptor. The boss ligand is expressed specifically on the surface of the R8 cell, whereas the sev receptor is expressed on 5 cells contacting the developing R8 cell and other cells not in contact with R8. By altering the spatial and temporal expression of boss, we demonstrate that sev-expressing cells that do not contact R8 can assume an R7 cell fate. By contrast, the sev-expressing precursor cells to the R1-R6 photoreceptor cells that do contact R8 are nonresponsive to the inductive cue. Using the rough and Nspl mutations, we demonstrate that an early commitment to an R1-R6 cell fate blocks the pathway of sev activation in these cells. PMID- 1760843 TI - The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. AB - Development of the Drosophila CNS midline cells is dependent upon the function of the single-minded (sim) gene. Sequence analysis shows that sim is a member of the basic-helix-loop-helix class of transcription factors. Cell fate experiments establish that sim is required for early events in midline cell development, including a synchronized cell division, proper formation of nerve cell precursors, and positive auto-regulation of its midline expression. Induction of ectopic sim protein under the control of the hsp70 promoter shows that sim can direct cells of the lateral CNS to exhibit midline cell morphology and patterns of gene expression. We propose that sim functions as a master developmental regulator of the CNS midline lineage. PMID- 1760844 TI - The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation. AB - Peptides corresponding to the proposed coated pit internalization signal of the native low density lipoprotein receptor, NPVY, take up in aqueous solution a reverse-turn conformation with the Asn in position i and the Tyr in position i + 3. By contrast, peptides derived from receptors that are defective for endocytosis do not adopt the reverse turn. These internalization-defective receptors include those with a nonaromatic residue substituted for the Tyr and those with Asn----Ala or Pro----Ala substitutions. While the tendency of an Asn Pro sequence to induce a reverse turn was anticipated, the structural importance of an aromatic residue in position i + 3 was not. The sequences associated with the internalization signal thus appear to play a critical conformational role that is required for endocytosis, probably by enabling binding to adaptor molecules. With the results presented in the accompanying paper on lysosomal acid phosphatase, we now have direct evidence for previous proposals of a general correlation of internalization signals with a turn conformational motif. PMID- 1760845 TI - The essential tyrosine of the internalization signal in lysosomal acid phosphatase is part of a beta turn. AB - For rapid endocytosis lysosomal acid phosphatase requires a Tyr-containing signal in its cytoplasmic domain, as do cell surface receptors mediating endocytosis and clustering in coated pits. To determine the structure of the internalization signal an 18 amino acid peptide representing the cytoplasmic tail of lysosomal acid phosphatase was analyzed by two-dimensional nuclear magnetic resonance spectroscopy. Part of the peptide, 5-PPGY-8, forms a well-ordered beta turn of type I in solution. Our result and data on the structure of the endocytosis signal of the low density lipoprotein receptor reported by Bansal and Gierasch in the accompanying paper represent experimental determinations of the three dimensional structure of protein transport signals and suggest that the essential aromatic amino acid of internalization signals is recognized by a putative cytoplasmic receptor in the structural context of a tight turn. PMID- 1760846 TI - HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. AB - Retroviral DNA integration involves a coordinated set of DNA cutting and joining reactions. Linear viral DNA is cleaved at each 3' end to generate the precursor ends for integration. The resulting recessed 3' ends are inserted into target DNA by a subsequent DNA strand transfer reaction. Purified HIV-1 integration protein carries out both of these steps in vitro. Two novel forms of the dinucleotide cleaved from HIV-1 DNA were identified and one, a cyclic dinucleotide, was used to analyze the stereochemical course of viral DNA cleavage. Both viral DNA cleavage and DNA strand transfer display inversion at chiral phosphorothioates during the course of the reaction. These results suggest that both reactions occur by a one-step mechanism without involvement of a covalent protein-DNA intermediate. PMID- 1760847 TI - TFIID binds in the minor groove of the TATA box. AB - We have analyzed the interaction of the general RNA polymerase II transcription factor TFIID with its DNA-binding site, the TATA box (consensus sequence TATAAAA). We have demonstrated that TFIID, unlike most sequence-specific DNA binding proteins, interacts primarily within the minor groove of the DNA helix. This was established by a novel approach involving complete replacement of the thymines and adenines in the TATA box with cytosines and inosines, respectively. This substitution exchanged the major groove of TATAAAA for that of the sequence CGCGGGG, without altering the surface of the minor groove. The unusual DNA binding properties of TFIID revealed by this study have important implications for TFIID specificity and function and, more generally, for sequence-specific recognition by DNA-binding proteins. PMID- 1760848 TI - Interaction of TFIID in the minor groove of the TATA element. AB - TFIID binding in the minor groove of DNA at the TATA element was demonstrated by methylation interference and hydroxyl radical footprinting assays, and by binding studies with thymine analog substituted oligonucleotides. These results provide an explanation for TFIID-dependent DNA bending at the TATA element. TFIID binding shows phosphate contacts with the same residues that were found to be essential for TFIID interactions by methylation and thymine-specific modification interference assays. Based on previous studies implicating residues conserved between the direct repeats in DNA binding, as well as models of prokaryotic DNA binding proteins, these results also suggest a model in which the direct repeats of TFIID form two basic antiparallel beta ribbon arms that could contact DNA through the minor groove. PMID- 1760849 TI - Detection of novel secondary metabolites. AB - The study of antibiotics and other fermentation products has shown that a seemingly unlimited number of compounds with diverse structures are produced by microorganisms. The continued high rate of discovery of new chemical entities, in the light of the abundance of microbial products already described, is due to creative screening procedures that incorporate such features as the emphasis on unusual microorgnaisms, their special propagation and fermentation requirements, supersensitive and highly selective assays, genetic engineering both for the biosynthesis of new compounds and in the development of screening systems, early in vivo evaluation, improved isolation techniques, modern procedures for structure determination, computer-assisted identification, and an efficient multidisciplinary approach. This review focuses on the genesis and development of the gamut of methodologies that have led to the successful detection of the wide variety of novel secondary metabolites that include antibacterial, antigungal, antiviral and antitumour antibiotics, enzyme inhibitors, pharmacologically and immunologically active agents, products useful in agriculture and animal husbandry, microbial regulators, and other compounds for which no bioactive role has yet been found. PMID- 1760850 TI - Principles and biotechnological applications of bacterial ice nucleation. AB - Certain aerobic, Gram-negative bacteria, including the epiphytic plant pathogen, Pseudomonas syringae, possess a membrane protein that enables them to nucleate crystallization in supercooled water. Currently, these ice-nucleating (IN) bacteria are being used in snow making and have potential applications in the production and texturing of frozen foods, and as a replacement of silver iodide in cloud seeding. A negative aspect of these IN bacteria is frost damage to plant surfaces. Thus, of the various types of biological ice nucleators, bacteria have been the subject of most research and also appear relevant to the anticipated practical uses. The intent of this review is to explain the identification and ecology of the ice-nucleating bacteria, as well as to discuss aspects of molecular biology related to ice nucleation and consider existing and potential applications of this unique phenomenon. PMID- 1760851 TI - Reduced cardiotoxicity of doxorubicin given in the form of N-(2 hydroxypropyl)methacrylamide conjugates: and experimental study in the rat. AB - A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of three N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg; P less than 0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age matched control rats (P less than 0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0.05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1760852 TI - Treatment of DNA with ammonium bicarbonate or thiourea can lead to underestimation of platinum-DNA monoadducts. AB - Thiourea and NH4HCO3 are widely used to block the conversion of Pt-DNA monoadducts to diadducts prior to the enzymatic digestion of DNA and subsequent analysis of the relative proportion of the different types of Pt-DNA adducts. Our data show that NH4HCO3 (100 mM, 18 h, 25 degrees C) is much less effective than thiourea (10 mM, 10 min, 25 degrees C) at blocking monoadducts, apparently because considerable monoadduct-to-diadduct conversion occurs during the incubation of platinated DNA with NH4HCO3. Under these incubation conditions, neither NH4HCO3 nor thiourea treatment causes significant diadduct-to-monoadduct conversion. At 25 degrees C, thiourea causes no significant removal of either ethylenediamine(en)- or diaminocyclohexane(dach)-Pt monoadducts. However, at 37 degrees C, both en-Pt and dach-Pt monoadducts are selectively removed. Pt-DNA diadducts are stable to 10 mM thiourea at either temperature. These data suggest that previous experiments using NH4HCO3-blocked DNA are likely to have underestimated Pt-DNA monoadducts and to have overestimated diadducts. As a consequence, such studies are likely to produce inaccurate estimates for the repair of individual adducts. The data also show that although thiourea treatment is suitable for blocking Pt-DNA monoadducts under the conditions generally used (10 mM, 10 min, 25 degrees C), it can selectively remove Pt-DNA monoadducts at higher temperatures. PMID- 1760853 TI - Polymer-coated albumin microspheres as carriers for intravascular tumour targeting of cisplatin. AB - We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration. Two systems were developed. PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only. PLAGA-coated microspheres displayed a mean diameter of 31.8 +/- 0.9 microns and a payload of 7.5% cDDP (w/w). Solid PLAGA microspheres exhibited a mean diameter of 19.4 +/- 0.6 microns and a payload of 20% cDDP. Release characteristics and in vitro effects on L1210 leukemia and B16 melanoma cell lines were investigated. Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began. PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining. Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP. Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix. The colony-forming ability of B16 cells was also equally inhibited by standard cDDP and pre-released drug. These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue. PMID- 1760854 TI - Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2'-deoxyuridine derivative. AB - 1-(3-O-Benzyl-2-deoxy-beta-D-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3)- pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED50 value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those for 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd), the parent compound of FTC-092, for 1-(2-tetrahydrofuryl)-5 fluorouracil (Tegafur, FT), the prodrug of 5-fluorouracil (FUra), and for FUra were 64.1, 122, and 28 mg/kg daily, respectively. The therapeutic indices (LD10/ED50) of FTC-092, CF3dUrd, FT, and FUra were 4.39, 1.7, 1.35, and 1.65, respectively. FTC-092 itself is not an active agent. After it has been absorbed from the gastrointestinal tract, FTC-092 undergoes a gradual biotransformation, mainly via the action of liver microsomes, releasing CF3dUrd over a long period. The levels of CF3dUrd in the stomach and small intestine of mice after the oral administration of FTC-092 were undetectable, whereas those following the administration of CF3dUrd at the same dose were high for a period of several hours. In contrast, the CF3dUrd level generated in plasma after the administration of FTC-092 remained at a high level for a longer period than did that observed on the administration of CF3dUrd. The low levels of CF3dUrd measured in stomach and small-intestine tissues and the maintenance of CF3dUrd in blood over long periods after the administration of FTC-092 are features that favor the possible clinical application of FTC-092. PMID- 1760855 TI - Multidrug resistance in MCF-7 human breast cancer cells is associated with increased expression of nucleoside transporters and altered uptake of adenosine. AB - The rate of adenosine uptake and the corresponding expression of nucleoside transporters were studied in several MCF-7 human breast-cancer cell lines that express different levels of multidrug resistance (MDR). Kinetic studies of adenosine transport in these cell lines revealed that the mean apparent Km and Vmax values for the nucleoside transporters increased with increasing MDR. The apparent Km and the apparent Vmax of Adriamycin-resistant (ADR10) cell lines were respectively 3.2- and 1.8- fold those of Adriamycin-sensitive wild-type (WT) cells (P less than 0.001). A partially revertant cell line (ADR10rev) that was derived from the ADR10 line and was partially sensitive to Adriamycin exhibited apparent Km and Vmax parameters that lay between those of the ADR10 and WT cells (P less than 0.001 vs ADR10 cells; P less than 0.05 vs WT cells). ADR10 cell membranes bound greater than 4 times more of the nucleoside transporter blockers [3H]-nitrobenzylthioinosine [( 3H]-NBI) and [3H]-dipyridamole [( 3H]-DPR) than did WT cell membranes per unit protein (P less than 0.0001). Scatchard analysis revealed a 2-3 times greater density for nucleoside transporters in ADR10 membranes as compared with those in WT membranes. ADR10rev membranes bound less [3H]-NBI and [3H]-DPR than did ADR10 membranes (P less than 0.001), but they bound more of the blockers than did WT membranes (P less than 0.05). A 2.5-h exposure to 200 nM phorbol-12,13-dibutyrate (PDBu), which activates protein kinase C (PKC) and induces WT cells to exhibit a 4-fold increased transient MDR phenotype, increased the apparent Km of WT cells for adenosine transport by greater than 2 times (P less than 0.001) to a value close to that found for the ADR10 cells. An identical exposure of ADR10 cells to PDBu produced no significant effect. The apparent Km of ADR10rev cells was increased 1.4 times by a 2.5-h PDBu exposure. None of the cell lines were affected by a 2.5-h exposure to 200 nM phorbol-13,10-diacetate (PDA), a much less active phorbol, or vehicle. These results suggest that MDR in MCF-7 cells is associated with changes in nucleoside transport, including both the number of transporters and their rate of transport, and that such changes can be partially mimicked by stimulation of PKC. PMID- 1760856 TI - Use of plasma cytotoxic activity to model cytotoxic pharmacodynamics of anticancer drugs. AB - We have developed a pharmacokinetic/pharmacodynamic approach that integrates the disposition, cytotoxic activity and interaction of anticancer drugs. Fundamental to this approach is the measurement of the cytotoxicity, against a "target" cell line, of patient plasma collected at different times after administration of the anticancer agent(s). To illustrate this approach, we have studied the plasma cytotoxic activity (PCA), against HL-60 cells, of plasma from 11 acute myeloblastic leukemic patients treated with daunorubicin (DNR). Plasma, obtained before and serially for 24 h after DNR treatment, was assayed by HPLC for DNR and daunorubicinol (DNRol), its active metabolite. The corresponding observed PCA values (PCAobs) against HL-60 cells were also measured with a flow-cytometric cell-survival assay that we had developed previously. The pharmacodynamics, i.e. PCA, were co-modeled (dual Hill equation with an interaction term to allow synergism or antagonism) with the pharmacokinetics. The integration of the PCA profile provided the area under the observed PCA versus time curve (AUCobs). For each patient, we also generated an "interaction panel", by adding known amounts of DNR and DNRol to his or her pretreatment plasma. The corresponding cytotoxicities were measured, and then applied to the pharmacodynamic model. This provided a standard surface from which the PCA of each sample obtained after therapy was predicted (PCAprd), on the basis of assayed concentrations of DNR and DNRol in that sample. For plasma samples obtained after treatment, the model simultaneously fit all three outputs, i.e. PCA and DNR/DNRol concentration, very well. We observed substantial interpatient variability in HL-60 growth rate in medium containing patient pretreatment plasma, in DNR activity in pretreatment plasma, and in the in vitro activity (PCA) of plasma obtained after DNR treatment. We also compared the AUCprd to the AUCobs for each patient, and we identified a subset of 4/11 acute myeloblastic leukemic patients who had developed much more PCA after DNR administration that could be explained by the measured concentrations of DNR and DNRol. This may be due to unidentified active metabolites or to factors produced in the plasma in response to the treatment. This pharmacokinetic/pharmacodynamic model is promising to describe pharmacodynamics and interactions of anticancer drugs in cancer patients. PMID- 1760857 TI - The effects of doxorubicin and mitoxantrone on wound healing. AB - The goal of the present study was to determine whether mitoxantrone would impair wound healing to a similar degree as doxorubicin when given in equally cytotoxic doses. On day 0, male Fischer rats were wounded and treated with 5% dextrose (control), 6 mg/kg doxorubicin, or 1.2 or 2.4 mg/kg mitoxantrone. On day 5, WBCs for the doxorubicin group and the group that had been treated with 1.2 mg/kg mitoxantrone were 33% and 43% lower than control values, respectively. All rats that had been given 2.4 mg/kg mitoxantrone died within 1 week of being wounded due to drug toxicity. On day 21, wound-breaking strength (WBS) analysis was performed: two skin specimens were taken from each dorsal skin incision perpendicular to the scar axis and were subjected to wound disruption (grams of force) by uniaxial extension. The WBS analysis indicated significant differences between the doxorubicin treated group (1183 +/- 96 g) and the control group (2422 +/- 247 g). However, no significant difference was found between the group that had been given 1.2 mg/kg mitoxantrone (2140 +/- 191 g) and control animals. Thus, mitoxantrone seems to exert myelosuppressive effects similar to those displayed by doxorubicin, but the former drug results in significantly less impairment of wound healing in the rat model. PMID- 1760858 TI - Somnolence, hypotension, and metabolic acidosis following high-dose teniposide treatment in children with leukemia. AB - This report describes an unexpected adverse effect in three children receiving teniposide at 3-5 times the conventional dosage (i.e. 200 mg/m2) plus cytarabine as part of continuation therapy for acute lymphocytic leukemia. Pharmacokinetic studies in each patient had demonstrated high teniposide clearances, and thus the increased dosage requirements were necessary to attain plasma concentrations similar to those expected for patients with average drug clearance. At 3-4 h after the beginning of the 4-h simultaneous infusions of teniposide and cytarabine, these patients experienced somnolence, hypotension, and metabolic acidosis. The adverse events were associated with elevated teniposide plasma concentrations during the infusions compared with those in patients receiving similar doses without toxicity, and clinically significant ethanol concentrations, presumably from the teniposide formulation. Blood concentrations of cremophor and histamine, which are also constituents of the teniposide formulation, were not measured. In addition, concomitant therapy with antiemetic agents in patients who may have been mildly volume-depleted due to emesis may also play a contributory role. Prolonging the infusion time for patients receiving teniposide doses above 500 mg/m2 will avoid excessive teniposide and ethanol plasma concentrations and minimize the risk of this potentially serious side effect. PMID- 1760859 TI - Clinical pharmacokinetics of mitoxantrone in hyperthermic, isolated perfusion of the leg. AB - The clinical pharmacokinetics of mitoxantrone in hyperthermic, isolated perfusion of the leg were studied in five patients exhibiting solitary, localized malignant melanoma. Mitoxantrone was given as four 1-min infusions at 15-min intervals into the arterial line of the perfusion system at a total dose of up to 14 mg/m2. The mean half-lives for mitoxantrone in the blood circulation of the leg were: t1/2 alpha (distribution phase), 25.5 s, and t1/2 beta (elimination phase), 14.9 min. The mean volume of distribution at steady state in the leg was 25.6 1. In the arterial part of the perfusion, the mean AUC was 155.9 mg min l-1, and that in the corresponding venous part was 91.6 mg min l-1. Leakage of the drug from the leg into the systemic circulation amounted to 1.2% of the total delivered dose; 91% of the delivered dose remained in the leg after the perfusion had been completed. The mean elimination half-life of mitoxantrone in the systemic circulation was 123 min and the corresponding AUC for systemic concentrations was 8.59 mg min l-1. The present data revealed a high uptake of mitoxantrone into the leg and low systemic drug concentrations due to minor leakage, suggesting that mitoxantrone might be a good candidate for use in isolated, hyperthermic limb perfusion. PMID- 1760860 TI - Cancer chemotherapy in the elderly: a series of 51 patients aged greater than 70 years. AB - A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were greater than 70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was greater than or equal to 70% for 40 patients. Malignancies were hematopoietic in 24 cases (47%) and digestive in 15 patients (29%), and 12 subjects (24%) had other types of cancers. The first chemotherapy course was given at the full dose to 23/51 (45.1%) patients. The drug dose was reduced for 28/51 (54.9%) patients, due in 25 cases to the subjects being greater than 70 years old. Neither age, KPS, pretreatment assessment, nor cancer extent was correlated with the modifications made to the first cycle. An overall toxicity of grade 3 + 4 (WHO grading scale) was noted in 10 subjects (19.6%). Although these elderly patients were probably selected, analysis of their charts did not evidence an increase in chemotherapy toxicity, regardless of the dose they received. PMID- 1760861 TI - Combined haemoperfusion, haemofiltration and haemodialysis for systemic detoxification in locoregional 5-fluorouracil therapy. AB - Combined haemoperfusion, haemofiltration and haemodialysis (HPFD) was examined for its systemic effect on 5-fluorouracil (5-FU) kinetics after locoregional application to one female patient with liver metastases of a colon carcinoma. During each HPFD treatment, which lasted 4 h, 5-FU was given via a port-a-cath system into the hepatic artery on 4 separate days. The HPFD extraction rate was 99%. Extracorporal 5-FU clearance (89 ml/min) was 9% of total body clearance (1094 ml/min). The fraction eliminated within 4 h was only 6% of the applied dose (3500-4000 mg 5-FU). Sufficient extracorporal detoxification during combined HPFD can thus not be guaranteed in locoregional chemotherapy with a high dose of 5-FU. PMID- 1760862 TI - Local treatment of cutaneous and subcutaneous metastatic malignant melanoma with fotemustine. AB - Fotemustine is a highly reactive chloroethyl-nitrosourea anti-tumor drug that is currently undergoing phase III clinical trials in stage IV metastatic malignant melanoma. The drug is a potent alkylating agent and rapidly chloroethylates the active sites of the important thioproteins thioredoxin reductase (TR), glutathione reductase (GR) and ribonucleotide reductase (RR). These enzymes control ribonucleotide reduction and, consequently, DNA synthesis in the S phase of the cell cycle. Side effects are minor due to the rapid metabolism of the drug. [14C]Fotemustine exhibited a half-life of 90 min in the vascular system after the administration of 100 mg/m2. Fotemustine was shown to yield the volatile degradation product acetylene (a) in distilled water (4.1%/h), (b) in melanoma cell culture medium (MCDB) supplemented with 10% fetal calf serum (33%/h) and (c) in fotemustine-sensitive human melanoma cells in culture medium (70.5%/h). Due to its rapid metabolism and its low toxicity, high concentrations of fotemustine (55 x 10(-3) M) were injected directly into cutaneous and subcutaneous melanoma metastases (n = 36) of seven patients, resulting in minor necrosis followed by total remission of the metastases. Untreated metastases adjacent to the treated tumors were not affected by fotemustine, confirming that rapid local metabolism of this drug occurs only in the vicinity of injected tumors without producing any systemic effects. PMID- 1760863 TI - Affinity of antineoplastic amino acid drugs for the large neutral amino acid transporter of the blood-brain barrier. AB - The relative affinity of six anticancer amino acid drugs for the neutral amino acid carrier of the blood-brain barrier was examined in rats using an in situ brain perfusion technique. Affinity was evaluated from the concentration dependent inhibition of L-[14C]-leucine uptake into rat brain during perfusion at tracer leucine concentrations and in the absence of competing amino acids. Of the six drugs tested, five, including melphalan, azaserine, acivicin, 6-diazo-5-oxo-L norleucine, and buthionine sulfoximine, exhibited only low affinity for the carrier, displaying transport inhibition constants (Ki, concentrations producing 50% inhibition) ranging from 0.09 to 4.7 mM. However, one agent - D,L-2-amino-7 bis[(2-chloroethyl)amino]- 1,2,3,4-tetrahydro-2-naphthoic acid (D,L-NAM) - demonstrated remarkably high affinity for the carrier, showing a Ki value of approximately 0.2 microM. The relative affinity (1/Ki) of D,L-NAM was greater than 100-fold that of the other drugs and greater than 10-fold that of any compound previously tested. As the blood-brain barrier penetrability of most endogenous neutral amino acids is related to their carrier affinity, the results suggest that D,L-NAM may be a promising agent which may show enhanced uptake and distribution to brain tumors. PMID- 1760864 TI - D-3-deoxy-3-substituted myo-inositol analogues as inhibitors of cell growth. AB - A number of unnatural D-3-deoxy-3-substituted myo-inositols were synthesized and their effects on the growth of wild-type NIH 3T3 cells and oncogene-transformed NIH 3T3 cells were studied. The compounds were found to exhibit a diversity of growth-inhibitory activities and showed selectivity in inhibiting the growth of some transformed cells as compared with wild-type cells. Remarkably, D-3-deoxy-3 azido-myo-inositol exhibited potent growth-inhibitory effects toward v-sis transformed NIH 3T3 cells but had little effect on the growth of wild-type cells. The growth-inhibitory effects of the myo-inositol analogues were antagonized by myo-inositol. Since [3H]-3-deoxy-3-fluoro-myo-inositol was shown to be taken up by cells and incorporated into cellular phospholipids, we suggest that these unnatural myo-inositol analogues may act as antimetabolites in the phosphatidylinositol intracellular signalling pathways. Because cells transformed by oncogenes often exhibit elevated phosphatidylinositol turnover, the inhibition of signalling pathways that mediate oncogene action could offer new opportunities for controlling the growth of cancer cells. PMID- 1760865 TI - Characterization of beta-endorphin-related peptides in the caudal medulla oblongata and hypothalamus of the prenatal, postnatal and adult rat. AB - A comparison was made of beta-endorphin (B-END) concentrations versus post translation products during the perinatal period in the hypothalamus and the caudal medulla oblongata. The concentration of B-END-like immunoreactivity did not differ statistically between embryonic day 21 (E21) and postnatal day 1 (P1) in either area. There were significant differences in forms, with a shift from larger precursors at E21 to smaller peptides at P1, with the predominant form of B-END being the 31 residue form at E21 in both regions. B-END varied between the two regions at P1, the 27-26 residue predominant in the hypothalamus, and the 31 residue in the caudal medulla. PMID- 1760866 TI - Neuromuscular contacts in the developing rat soleus depend on muscle activity. AB - Neuromuscular transmission of the rat soleus muscle was interrupted by blocking the response of the postsynaptic membrane with alpha-bungarotoxin (alpha-BTX) at two different stages of postnatal development, i.e., at birth and at 10 days. The effect of this treatment on the maintenance of synaptic contacts was studied using histological and electrophysiological criteria. Following treatment at birth fewer muscle fibres were polyneuronally innervated 5-7 days later. After this initial loss of synaptic contacts, the subsequent rate of synapse elimination was slower than in control animals, so that even at 3 weeks muscles treated with alpha-BTX at birth had higher levels of polyneuronal innervation than their unoperated controls. Thus, interference with the response of the postsynaptic membrane at birth has prolonged effects on synaptic development. In muscles treated with alpha-BTX at 10 days the elimination of polyneuronal innervation was arrested and more neuromuscular contacts preserved. PMID- 1760867 TI - The effects of bilateral enucleation in the primate fetus on the parcellation of visual cortex. AB - Bilateral enucleation in the macaque fetus causes an areal reduction of an otherwise normal striate cortex. Here we show that in early operated animals this reduction is accompanied by a separation of striate and prostriate cortices which are normally contiguous. However this induced separation does not correspond to the areal reduction of striate cortex, indicating that extrinsic signals regulate either the proliferation and/or survival of striate cortical neurons. PMID- 1760868 TI - Effects of dark-rearing on the retinal dopaminergic system in the neonatal and postnatal guinea pig. AB - To appraise the extent of light responsivity of the retinal dopaminergic system in the early postnatal period, dopamine content (DA) of retinas of cycling-light reared and dark-reared guinea pigs was determined. DA storage postnatally was suppressed in dark-reared animals. Their retinas responded to a brief light stimulus by rapidly increasing DOPA synthesis and DA utilization, but not to the extent of the response of cycling-light-reared animals. Dopaminergic retinal neurones depend on light stimulus for the complete development of some of their neurochemical characteristics. PMID- 1760869 TI - The intracortical position of pyramidal tract neurons in the motor cortex of the reeler changes from postnatal day 10 to adulthood. AB - To determine whether or not the intracortical distribution pattern of pyramidal tract (PT) neurons in the motor cortex (hindlimb area) of normal and reeler mutant mice changes during early postnatal development of the cortex, we injected HRP into the pyramidal decussation of postnatal day (P) 8 and adult animals of the normal and reeler strains, and killed the animals 2 days later. In the normal P10 and adult mice, such an injection resulted in a band of labelled neurons confined to the layer of large pyramids (LP), suggesting that the intracortical localization of PT neurons does not change from P10 to adulthood in the normal strain. In the P10 and adult reeler mice, labelled PT neurons were scattered radially from the deepest zone to the superficial zone of the motor cortex. However, while the HRP-labelled PT neurons are located bilaminarly in both the deepest zone and the superficial zone of the motor cortex of the P10 reeler mouse, the majority of PT neurons were found in the upper third of the motor cortex of the adult reeler mouse. Thus, the intracortical distribution pattern of PT neurons of the reeler mouse changes during the postnatal period. PMID- 1760870 TI - Prenatal nicotine exposure selectively affects perinatal forebrain aromatase activity and fetal adrenal function in male rats. AB - Previous studies have revealed effects of prenatal nicotine treatment on fetal plasma testosterone and perinatal sexual brain differentiation in the rat. In an attempt to further elucidate the processes underlying this action of nicotine, we studied the effect of the drug on brain steroid aromatase which converts androgens to estrogens and is known to be important in sexual brain differentiation. Aromatase activity (AA) was measured by the conversion of [1 beta-3H]-androstenedione to estrone in a brain region comprising preoptic, hypothalamic and amygdaloid areas. In untreated animals, the development of AA between gestational day (GD) 18 and postnatal day (PN) 15 was similar in both sexes, except for a significant drop of AA in female brain at PN6, i.e., during the later part of the critical period for sexual brain differentiation. When time pregnant rats were treated with nicotine delivered by an osmotic minipump for either one week (2 mg/kg/d or 6 mg/kg/d from GD12) or two weeks (6 mg/kg/d from GD8), their male offspring showed a decrease of AA to female levels at PN6, the sex difference existing at this stage thus being abolished. AA of offspring from dams bearing tartaric acid-containing minipumps or sham-operated at GD8 or GD12 was identical to that of untreated controls. No drug effect was seen in female fetuses and offspring. Sex differences in the developmental effect of nicotine may thus involve brain aromatase. An additional sex-dependent effect of nicotine was observed in the male fetal adrenal axis at GD18. Whether the drug effects on the two steroid hormone systems are interrelated, remains to be elucidated. PMID- 1760871 TI - Ontogeny of proenkephalin gene expression in the rat hypothalamus. AB - In the rat hypothalamus, proenkephalin (PE) mRNA synthetizing cells were detected by in situ hybridization, using synthetic oligodeoxy-nucleotides, from embryonic day 14 (E14) in the presumptive anterior hypothalamic area (AHA) and preoptic part of the bed nucleus of the stria terminalis (BST), and from E18 in the developing median preoptic area, perifornical area, suprachiasmatic nucleus, dorsomedial and ventromedial hypothalamic nuclei. In the paraventricular nucleus, cells expressed PE gene in the late prenatal stages; both parvo- and magnocellular neurons synthetized PEmRNA in the early postnatal stages. Cells expressing PE gene were observed after birth in the lateral preoptic area, lateral hypothalamus, medial and lateral parts of the BST. PEmRNA was also found from E14 in the striatum, from E18 in the central and medial amygdaloid nuclei, the medial group of the thalamic nuclei, and postnatally in a second more anterior structure of the thalamus. In the hypothalamus, a clear similarity was observed between adult and developmental distributions of PE gene expressing cells. The early onset of PE gene expression in the developing rat diencephalon suggests an involvement of PE in developmental processes, such as cell proliferation and differentiation; the presence of PE during the perinatal period may also indicate the appearance of adult neural regulations. PMID- 1760872 TI - Developmental expression of the basic fibroblast growth factor gene in rat brain. AB - Basic fibroblast growth factor (bFGF) is a trophic factor for a variety of neuronal/glial cell populations. The RNase protection assay, with a cRNA complementary to the coding region of bFGF mRNA, was used to investigate the brain distribution and developmental regulation of bFGF mRNA expression. In adult rats bFGF mRNA is distributed throughout the brain, the highest levels being observed in cerebral cortex, hippocampus and spinal cord. The levels of bFGF mRNA in all the brain structures are low in newborn rats, increase thereafter to reach a peak of expression around postnatal day 21. bFGF mRNA levels are significantly different between various brain structures during the first and second postnatal week. Adult and aged rats (Fisher 344) express the same levels of bFGF mRNA in the various brain regions. The onset of bFGF mRNA expression suggests that this growth factor is important for the maturation as well as for the maintenance of different cell populations of the central nervous system. PMID- 1760873 TI - Postnatal development of corticosteroid receptor immunoreactivity in the rat hippocampus. AB - Postnatal changes in corticosteroid receptor immunoreactivity in the rat hippocampus were examined using an antiserum against a fusion protein containing an N-terminal peptide of the Type I receptor, and a monoclonal antibody against the rat liver Type II-receptor. Age-related regional differences were observed. In the pyramidal cell layer of Ammon's horn, and granule cell layer of the dentate gyrus (DG), the percentage of Type I receptor immunoreactive (Type I-ir) and Type II receptor immunoreactive (Type II-ir) cells was high perinatally, declined sharply by postnatal day 10 (P10), and showed a variable increase to adult levels subsequently. The pyramidal cells of CA1-CA2, subiculum and DG showed a selective increase in Type II-ir in late postnatal life into adulthood, while most other regions showed higher Type I-ir in both early and late postnatal life, suggesting different roles for these receptors during development. Type II ir was predominantly nuclear in most neurons, except for a transient appearance of cytoplasmic Type II-ir in neurons of the stratum oriens and molecular layers of Ammon's horn and dentate gyrus of P20-P30. Type I-ir was diffusely nuclear and cytoplasmic at all developmental ages. This is suggestive of differential genomic and extragenomic roles for these receptors during postnatal development of the hippocampus. PMID- 1760874 TI - Role of laminin in stimulating rapid-onset neurites in NG108-15 cells: relative contribution of attachment and motility responses. AB - The present paper analyzed how attachment and motility responses contribute to the initial formation of rapid-onset neurites in undifferentiated NG108-15 cells. Attachment responses played a positive role in stabilizing neurites against slippage, but exerted a negative effect upon active motility--which appears to be the major rate-determining event in initial outgrowth. The role of laminin in this paradigm was elucidated by analyzing the effects of polyglutamate and other agents (bovine serum albumin and polyethylene glycol chain derivatives) which reduced the number of passive substratum attachment sites, but which did not affect cells directly nor affect the binding of laminin to the substratum. Polyglutamate decreased attachment and spreading of cells, yet greatly accelerated the initial laminin-dependent formation of rapid-onset neurites, and greatly enhanced active neurite remodelling and cell translocation as well. Together with data presented in previous studies in this series, these findings indicate that laminin stimulates rapid-onset neurites primarily by stimulating active motility responses. Insofar as rapid-onset neurites appear to provide a valid model of how neuronal growth cones are regulated, it is likely that these findings will be relevant to developing primary neurons as well. PMID- 1760875 TI - Differential hormonal modulation of brain antigens recognized by the AB-2 monoclonal antibody. AB - The expression of monoclonal antibody AB-2 immunoreactivity is age- and sex dependent in radial glia of developing rat hypothalamus and is regulated by prenatal exposure to gonadal steroids. In the present study, several proteins were recognized by AB-2 and were distributed selectively in subcellular fractions from neonatal hypothalamus (HYP), remaining forebrain (FB), and brainstem regions. Immunoblots revealed polypeptide bands in 3 major molecular weight classes: one at approximately 195 kDa in the cytosolic compartment; and two doublets at 220 kDa and 340 kDa in both microsomal and crude mitochondrial membrane fractions. The 220 kDa and 340 kDa doublets were also Triton-insoluble, suggesting a cytoskeletal association. The 195 kDa-AB-2-immunoreactive band was present in both Triton-soluble and insoluble fractions. AB-2 also recognized several acidic glycolipids extracted from postnatal rat brain regions on immunoblots following high performance thin layer chromatography. One of the bands from postnatal rat brain extracts migrated similarly to purified bovine brain sulfatide, which was also immunoreactive with AB-2. AB-2 immunoreactivity with proteins, polar lipids, and sulfatide suggests that the epitope is a carbohydrate present in multiple cellular compartments. AB-2 recognized the same molecular bands in males and females. Testosterone treatment selectively decreased the level of the 195 kDa AB-2-immunoreactive polypeptide. The 195 kDa AB-2-immunoreactive polypeptide possibly acts in radial glia in the determination of sexually dimorphic neurons in the preoptic area/hypothalamus. PMID- 1760876 TI - Establishment of photoreceptor cell polarity in culture revealed by mushroom lectin binding. AB - Differentiation of photoreceptor cells dissociated from chick embryo was investigated in a monolayer culture at low cell density and low serum concentration. The precursor cells were initially round and finally adopted the elongated and monopolar shape characteristic of such photoreceptor cells in vivo. They exhibited the primitive inner segment, and on its distal side showed a crest like membrane expansion instead of the developed outer segment. The cell polarity of these cultured photoreceptor cells was examined using mushroom lectin, which has specific affinity for the D-galactose-beta(1,3)-N-acetylgalactosamine moiety. Rhodamine-labeled mushroom lectin uniformly initially stained the surface of early round photoreceptor cells, but with time the staining became restricted to the inner segment and its distal membrane expansion in all elongated photoreceptor cells at 12 days from the beginning of development. In semithin sections of 12-day-old chick embryo retina, mushroom lectin also stained the immature inner segment that had emerged at this stage. After hatching, light and electron microscopic observations revealed that the entire scleral surface of retinal plasma membranes as far as the outer limiting membrane, i.e. the inner and outer segments of all types of photoreceptor cells and also Muller cell processes, were stained with the mushroom lectin. These results clearly show that all photoreceptor cells can establish their inherent cell polarity even in culture, and that mushroom lectin is a valuable marker, for the investigation of photoreceptor cell polarity. PMID- 1760877 TI - Growth factor and oncogene signalling pathways as targets for rational anticancer drug development. AB - There is a critical need for new targets, in addition to DNA, for anticancer drug development. A recently discovered target is the intracellular signalling pathways that mediate the actions of growth factors and oncogenes on cell proliferation. Two important pathways, the myo-inositol and protein tyrosine kinase signalling pathways are reviewed. Three classes of compounds that modulate myo-inositol signalling are discussed. These are: 1) the D-3-substituted-3-deoxy myo-inositol analogues that act as antimetabolites of myo-inositol and show selective growth inhibition of some transformed cells; 2) the alkaloid staurosporine that acts as a potent inhibitor of protein kinase C and of platelet derived growth factor (PDGF) receptor protein tyrosine kinase activity; 3) the ether lipid analogues that block growth factor signalling at several points by acting as inhibitors of protein kinase C, phosphoinositide specific phospholipase C and inositol(1,4,5)trisphosphate-induced Ca2+ release. It is suggested that inhibition of signalling pathways may explain the growth inhibitory effects of these compounds. Other potential signalling target sites for anticancer drug development are discussed. PMID- 1760878 TI - Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. I. Isolation, purification and preliminary characterization. AB - We describe the purification and initial characterization of a hitherto unrecognized fluorescence (excitation/emission maxima at 380/440 nm and 400/460 nm) reported from this laboratory in patients with chronic renal failure (Clin Chem 31: 1988, 1985). Purification was achieved using Sephadex G-10 gel chromatography combined with reverse phase and ion exchange high-performance liquid chromatography (HPLC). Purity of the "blue-green" fluorescent compound was determined to be greater than 99% by HPLC, and two-dimensional thin layer chromatography using an acidic and basic solvent system. The excitation/emission maxima were shown to be 390 nm/456 nm, and ultraviolet scans, at pH 1.0, 7.0, and 13.0, gave absorbance optima at 261 nm/356 nm, 278 nm/390 nm, and 255 nm/394 nm, respectively. The isoelectric point of 4.05 in conjunction with the fluorescent and ultraviolet spectra suggests that the fluorophore belongs to the class of compounds known as pteridines. PMID- 1760879 TI - Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. II. Biochemical elucidation and structural analysis. AB - We have identified the primary endogenous fluorescent substance, which has characteristic excitation/emission maxima at 380/440 nm and 400/460 nm, found in the sera of patients with chronic renal failure (Clin Chem 32: 1276, 1988). Preliminary studies, using thin layer chromatography (with cellulose) in conjunction with pteridine standards, indicated that the compound is an unconjugated pteridine. Characterization by gas chromatography-mass spectrometry (electron impact), direct probe-mass spectrometry (electron impact/chemical ionization), and Fourier Transform Infrared analysis showed this compound to be xanthopterin (2-amino 4,6 pteridinedione), an unconjugated pteridine known to be present in man in trace quantities. An authentic sample of this compound had a retention time with high-performance liquid chromatography (HPLC) identical to that of the purified fluorophore. The physiological role of xanthopterin in the pathogenesis of uremia has yet to be elucidated. PMID- 1760880 TI - Precipitation method for separating and quantifying bone and liver alkaline phosphatase isoenzymes. AB - We evaluated a method for quantifying bone isoenzyme of alkaline phosphatase (ALP) which utilizes wheat-germ lectin to precipitate this fraction. In precision studies, CVs ranged from 3.2 to 11.4% (within-day) and from 3.7 to 11.5% (day-to day). The assay procedure was linear to 1100 U/L and was easily adapted to automated kinetic measurement. Comparison of the precipitation method with an affinity electrophoretic method, which utilizes cellulose acetate as a support, demonstrated a satisfactory coefficient of correlation (r = 0.886). The reference range was determined in sera from 188 healthy adult subjects. The distribution of bone ALP values was also studied in 73 healthy children and in 30 healthy adolescents. To evaluate the clinical applicability of the method, the bone isoenzyme was determined in samples from several groups of subjects (pregnant women, patients with hepatobiliary diseases, patients with hepatocellular carcinoma without skeletal involvement, and patients with bone, liver or lymph node metastases). We found the method suitable for routine determination of bone alkaline phosphatase and for the screening of bone metastases. Because of its technical simplicity and satisfactory analytical performance, it can be used instead of the heat-inactivation procedure. PMID- 1760881 TI - A fast high-performance liquid chromatographic method for the measurement of plasma concentration and specific activity of phenylalanine. AB - A fast high-performance liquid chromatographic (HPLC) method for the measurement in plasma of phenylalanine concentration and specific activity is reported. One to-two mL of acidified plasma are applied to an ion-exchange resin. The eluted amino acids are enzymatically converted into the corresponding alpha-ketoacids, i.e. phenylalanine is converted into phenylpyruvic acid. After a two-step extraction, phenylpyruvic acid is separated by reverse phase chromatography within 8-10 min. The use of an internal standard allows precise quantitation of plasma concentrations. The radioactivity eluted from the HPLC is divided by the amount injected to yield the specific activity. Concentration and rate of appearance of phenylalanine in man, calculated with the L-[2,6-3H]-phenylalanine tracer, are in the range of published data. PMID- 1760882 TI - Heterogeneity of HDL in crossed immunoelectrophoresis with continuous gradient polyacrylamide gel in the first dimension and one or two antibody layers in the second dimension. AB - We describe a new method of immunoelectrophoresis with a continuous gradient polyacrylamide gel in the first dimension and an agarose-dextran gel in the second dimension with one or two layers of antibody. The use of a polyacrylamide gel in the first dimension allows better resolution of lipoproteins than with crossed immunoelectrophoresis using agarose gel in both dimensions. The use of two layers of antibody in the second dimension also enhances the specificity of characterization and the resolution of the separation. Thus, using a layer of anti-apo A-I combined with a layer of anti-apo A-II, three particles containing only apo A-I and three containing both apo A-I and A-II could be separated. PMID- 1760883 TI - Serum total free radical trapping ability in acute myocardial infarction. AB - Serum total free radical trapping abilities (TRAP experimental) were measured in 15 patients with acute myocardial infarction (AMI) and compared to sex- and age matched controls. TRAP experimental values were significantly lower (p less than 0.01) in the AMI group. Theoretical trapping abilities were also calculated and compared with experimentally derived values. In the AMI group there was no significant difference between the experimental and calculated TRAP, but in the control group experimental values were significantly higher (p less than 0.01) than calculated values. In the control group regression analysis revealed that alpha-tocopherol and ascorbate taken together most closely explained the radical trapping ability of sera, with a regression equation: TRAP experimental = 562.9 + 2.082 (alpha-tocopherol + ascorbate). In the AMI group no relationship between the serum antioxidants and TRAP experimental was observed. PMID- 1760884 TI - Phosphatase isoenzymes as bone metastasis markers in prostatic carcinoma. AB - Bone alkaline phosphatase (b-ALP) and tartrate resistant acid phosphatase (tr ACP) are markers of the activity of osteoblasts and osteoclasts, respectively. We have already shown that the serum activity of these isoenzymes was elevated in breast cancer patients with bone metastasis (BM); we show here that the serum activity of b-ALP and tr-ACP were also elevated in prostate cancer patients with BM. Specificity and sensitivity of b-ALP for BM were 0.90 and 0.75, respectively; and for tr-ACP, 0.60 and 0.60, respectively. The accuracy of b-ALP as a BM marker was higher than the accuracy of usual markers of prostatic carcinoma (tartrate labile ACP [tl-ACP], prostatic acid phosphatase [PAP] and prostate specific antigen [PSA]). The highest value predictive of a positive bone scan was obtained with b-ALP (0.88); this increased to 0.97 when b-ALP was coupled with PAP. PMID- 1760885 TI - Role of endogenous dopamine in the natriuretic response to various degrees of iso osmotic volume expansion in rats. AB - It is recognized that endogenous dopamine (DA) plays an important role in regulation of sodium excretion under certain physiological and experimental conditions. However, the relative contribution of intrarenally produced DA to natriuresis accompanying various degrees of acute volume expansion (VE) still remains to be clarified. In the present study, acute iso-osmotic VEs were performed in pentobarbital-anesthetized rats over a 60 min period. The rats were divided into 3 groups, each received either modest (2.5% body weight), moderate (5% body weight), or large degree of VE (10% body weight), respectively. Acute VE in these three groups evoked pronounced increases in urine output (UV) and urinary sodium excretion (UNaV), which were associated with significant increase in urinary DA excretion (UDAV). Compared to the modest VE (2.5% body weight), moderate VE (5% body weight) produced larger increases in UV (43 +/- 4.7 vs 29.0 +/- 4.7 microliters/min, p less than 0.05) and UNaV (7.8 +/- 0.7 vs 4.7 +/- 1.0 microEq/min, p less than 0.05) with slight but significantly greater increase in UDAV (1.38 +/- 0.06 vs 1.23 +/- 0.02 ng/min, p less than 0.05). Compared to moderate VE (5% body weight), large VE (10% body weight) produced more pronounced increases in UV (91 +/- 14 vs 43 +/- 4.7 microliters/min, p less than 0.01) and UNaV (16 +/- 2.3 vs 7.8 +/- 0.7 microEq/min, p less than 0.01), however the increase in UDAV was similar to that seen during moderate VE. These results suggest that endogenous DA is involved in natriuretic response to various degrees of acute VE. Furthermore, it was discovered that the relative contribution of endogenous DA to overall VE-induced natriuresis is related to some extent to the degree of VE, inasmuch as DA appears to play a greater role in the overall natriuretic response seen during modest to moderate degree of VE. PMID- 1760886 TI - Long term follow-up after surgical removal of pheochromocytoma--observations in 61 patients. AB - 89 patients were operated on for pheochromocytoma. 61 patients (37 women and 24 men) were available for extended follow-up. The final survey, performed 79.1 +/- 66.9 months postoperatively, provided data on survival, blood pressure tumor recurrence, malignant metastatic lesions, cardiovascular complications and coexisting diseases. There were 4 deaths during the follow-up period, including 2 instances of malignant pheochromocytoma. Permanent normalization of blood pressure was achieved in 38 patients (62.3%). This hypotensive effect was noted in 79.2% of patients with preoperative paroxysmal hypertension and in 40.8% of those with sustained hypertension. Permanent or re-developing postoperative hypertension was noted in 23 (37.7%) patients. This includes 4 cases of malignant pheochromocytoma, 4 cases of recurrent benign pheochromocytoma and 15 cases of essential hypertension. Cardiovascular complications during follow-up were rare and concerned the patients with essential hypertension diagnosed postoperatively. PMID- 1760887 TI - Obstructive sleep apnea syndrome in male hypertensives, refractory to drug therapy. Nocturnal automatic blood pressure measurements--an aid to diagnosis? AB - Sixteen therapy resistant hypertensive males and 16 responders to antihypertensive drug treatment, matched for age, gender and body mass index, were examined by means of Static Charge Sensitive Bed (SCSB) and oximetry for the presence of obstructive sleep apnea syndrome (OSAS). In borderline cases, polysomnography was performed. The prevalence of OSAS among therapy resistant patients was 56%, as compared to 19% in the control group (p less than 0.05). This higher prevalence of OSAS in a weight-matched group of subjects with severe hypertension supports the notion of a causal connexion between hypertension and OSAS. In 10 OSAS patients and 10 hypertensives with normal respiration during sleep, ambulatory noninvasive monitoring (ABPM) of arterial pressure (AP) and heart rate (HR) was also performed. The OSAS patients had a higher nocturnal variability of HR, systolic blood pressure (both p less than 0.05), and diastolic blood pressure (p less than 0.01) in 8 half-hourly single ABPM measurements. Contrary to the non-OSAS subjects they also had a higher HR variability during sleep than they had in the waking state (p less than 0.05). For subjects less than 60 yrs a range/median value of greater than 0.32 for nocturnal diastolic pressure was found to predict OSAS with a sensitivity of 87.5% and a specificity of 100%. It is concluded that therapy-resistant male hypertensives have a high prevalence of OSAS. As this may be a deleterious combination, screening for OSAS is highly indicated in such patients. A high variability of HR and AP in nocturnal ABPM suggests OSAS. PMID- 1760888 TI - Altered renin release from isolated superfused rat glomeruli in DOCA-salt hypertensive rats. AB - The present study was designed to clarify the role of calcium in suppressed renin release in DOCA-salt hypertension. Rat glomeruli were isolated by the modified Beierwaltes' sieving method. The glomeruli were superfused with Krebs-Ringer solution. Basal levels of renin release were lower in the DOCA-salt hypertensive rats (1.16 +/- 0.27 ng/ATI/hr/hr/10(4) glomeruli, mean +/- SEM, n = 8) than in the control rats (1.92 +/- 0.18, p less than 0.01, n = 8). Perfusion with a calcium free solution containing EGTA and A23187 stimulated renin release in the DOCA-salt hypertensive and control rats. The maximum levels of renin release during the perfusion in DOCA-salt hypertensive rats (1.79 +/- 0.17, n = 8) were lower than those in control rats (10.60 +/- 1.85, p less than 0.01, n = 8). These results suggest that high levels of intracellular calcium might not contribute to the suppression of renin release in DOCA-salt hypertension. PMID- 1760889 TI - Blood pressure and anthropometric differences in regularly exercising and nonexercising black adults. AB - Few studies have examined the relationship between exercise and BP in Black adults, a population with substantial risk for hypertension. This pilot study was undertaken to examine BP, anthropometric characteristics, dietary intake, and resting pulse rate by level of exercise participation in a group of Black Seventh Day Adventists. Subjects were classified as regular exercisers (n = 54, age = 54.6 yrs) if they reported at least two exercise sessions per week (x = 4.0 times per week) lasting a minimum of 20 minutes each, in which they engaged in vigorous exercise. Nonexercisers (n = 60, age = 56.2 yrs) were those who reported participation in such exercise no more than once per week (x = 0.1 times per week). There were no group differences in dietary intake of any macro or micronutrients, but exercisers exhibited significantly lower body mass index, waist circumference, triceps skinfold thickness, and resting pulse rate. Forty two percent of the nonexercisers were confirmed hypertensives compared to only 20 percent of the exercisers. Age and gender-adjusted BP was significantly lower in the exercisers (BP = 123.8/73.4 mm Hg) compared to the nonexercisers (BP = 133.5/77.1 mm Hg). After adjustment for anthropometric differences, the systolic BP of the exercisers remained approximately 8 mm Hg lower than their nonexercising counterparts. These data suggest that participation in vigorous exercise is favorably related to blood pressure and may attenuate the risk of hypertension in Black Seventh Day Adventists. PMID- 1760890 TI - Hypercholesterolemia and changes of vascular contractile responses in experimentally uremic rats. AB - Arterial contractile responses were studied in experimentally uremic rats. The ligation of 75% of the terminal branches of the left renal artery, followed by contralateral nephrectomy induced a chronic renal failure, as evidenced by significantly higher BUN concentrations and an elevation in blood pressure. Uremic rats exhibited elevations in total and HDL cholesterol, increased triglyceride levels, and significantly lowered HDL/total cholesterol ratios compared to control groups: 1) untreated control, 2) experimental control receiving renal infarction without contralateral nephrectomy, and 3) two kidney, one clip (2K1C) model of hypertension. Plasma total cholesterol levels in uremic rats increased by 50% in the first week following final surgery and plateaued at approximately 100% above control levels during postoperative weeks 3 through 10. Plasma transaminase levels were similar among all of the groups of rats studied indicating no effects of surgery on hepatic function. The contractile responses of aortic rings from uremic rats to submaximal concentrations of serotonin and clonidine were significantly increased and decreased, respectively, whereas the contractile response to norepinephrine was not altered. The enhanced sensitivity to serotonin of aortic rings from uremic rats was abolished following disruption of the endothelium. Neither the alteration of aortic contractile properties nor changes in plasma BUN and cholesterol concentrations were observed in hypertensive 2K1C rats. However, there was a tendency for decreased acetylcholine induced relaxation in aortic rings of uremic and 2K1C rats. No significant histological evidence of atherosclerosis was found in aortic tissues of uremic rats during the interval of study. These results indicate that hypercholesterolemia, hypertriglyceridemia, and altered vascular sensitivity to serotonin and clonidine are likely to be primary changes in the uremic rat and are not secondary to the development of blood pressure elevation or overt evidence of structural change in the vessels of this model. PMID- 1760891 TI - Calcium and the impairment of contractions to norepinephrine in aorta isolated from the spontaneously hypertensive rat. AB - Helical strip contractility from hypertensive (SHR) and normotensive (WKY) rat aortas assessed in the presence of varying calcium concentrations indicated that SHR strips exhibit a higher intrinsic myogenic tone and contract less to norepinephrine (NE) in a physiological calcium concentration compared to controls. Relatively higher isometric tension was developed in the SHR in low calcium (0-0. 27 mM). While control responses were blunted by LaCl3, EGTA, and nifedipine, the SHR strips were unaffected. Addition of procaine significantly enhanced SHR contractility to NE with no effect on control strips. These data suggest that abnormal cytosolic calcium provokes an increase in myogenic tone and an impaired contractile response of aortic smooth muscle cells to NE. PMID- 1760892 TI - Renal dopamine and changes in dopamine receptor ligand binding during high sodium intake. AB - This study was designed to measure changes in plasma levels of atrial natriuretic peptides (ANP), urine volume (UV), urinary excretion of dopamine (UDAV) and sodium (UNaV), and dopamine (DA) receptor affinity (Kd) and binding sites (Bmax) in kidneys of rats drinking normal saline for a period of 7 days. The saline intake significantly increased UV, UNaV, plasma ANP, UDAV, and its primary metabolite dihydroxyphenyl acetic acid (DOPAC) for the period of 7 days. Bmax increased significantly 1 day after the initiation of saline intake, however, the increase appeared to be transient since measurements of Bmax made after 7 days of saline intake were not significantly different from the control group. No changes in Kd were observed. These results indicate that renal DA contributes to maintenance of Na balance during increased Na intake and that renal DA receptors undergo transient changes during this period. PMID- 1760893 TI - Psychosocial stress elevates blood pressure via an opioid dependent mechanism in normotensive rats. AB - Stress is an important risk factor in cardiovascular diseases, including hypertension. Endogenous opioids are known to be elevated in stress and in various models of hypertension with differing etiologies. Blockade of endogenous opioids with naloxone has been demonstrated to attenuate or reverse the elevation in blood pressure in both renovascular and spontaneous hypertension. In the current study, increased blood pressure was induced using a model of psychosocial stress. During the first week of stress, systolic blood pressure rose rapidly to reach a level that was sustained throughout the remaining period of stress. Chronic infusion of the opiate antagonist, naloxone, both prevented and completely reversed the elevated blood pressure due to psychosocial stress. These data demonstrate that elevated endogenous opioids are important factors in cardiovascular regulation and are likely to influence both the development and maintenance of stress-induced hypertension. PMID- 1760894 TI - Development of a high renin model of hypertension in the cynomolgus monkey. AB - Hypertension was produced in cynomolgus monkeys by reducing blood flow to the left kidney by 60% via renal artery stenosis (2-kidney, 1-clip). Significant increases in mean arterial blood pressure (MABP) were observed within two to three weeks. Maximum increase (from 95 +/- 6 mmHg to 130 +/- 7 mmHg) occurred at about four to six weeks following renal artery stenosis and was sustained for more than 24 weeks. Plasma renin activity (PRA) was elevated concomitantly with the increase in MABP. PRA was raised to 42 +/- 3 ng angiotensin I/ml/hr six weeks after renal artery stenosis from a control PRA of 3 +/- 0.7 ng angiotensin I/ml/hr. At six months post renal artery stenosis, PRA was 33.4 +/- 4.2 ng angiotensin I/ml/hr. The angiotensin II (AII) receptor antagonist saralasin, the angiotensin I converting enzyme inhibitor captopril, and the renin inhibitor CGP 38,560 produced sustained reductions in MABP. The antihypertensive response to the renin inhibitor CGP 38,560 was associated with a reduction in PRA of greater than 99%, and a greater than 90% reduction in immunoreactive AII. These studies demonstrate that high-renin hypertension can be induced in the cynomolgus monkey. This pathological model provides a useful method for investigating the antihypertensive effects of agents which antagonize the renin-angiotensin system in a nonhuman primate. PMID- 1760895 TI - Mechanisms involved in angiotensin II induced increases in cardiac output in pithed rats. AB - This study was conducted to determine the mechanisms by which angiotensin II (Ang II) acutely increases cardiac output. Pithed Sprague-Dawley rats were prepared for continuous measurement of cardiac output by electromagnetic flowmetry. Ang-II (31-1000 ng/kg, i.v.) produced dose-related increases in cardiac output, heart rate and stroke volume. Although the heart rate increases were abolished by beta adrenoceptor blockade, the cardiac output responses were unchanged due to an offsetting increase in stroke volume. The constancy of the cardiac output response following beta-adrenoceptor blockade suggested that Ang-II increased cardiac output by constricting venous smooth muscle and thereby increasing venous return. This conclusion is supported by the observation that Ang-II produced marked increases in left ventricular end diastolic pressure that paralleled the increases in cardiac output. In fact, based on volume loading with Tyrode's solution, the changes in left ventricular end diastolic pressure produced by Ang II should have resulted in even greater increases in cardiac output. However, it appears that the significant rise in peripheral resistance to Ang-II tended to counter the effects of increased venous return on cardiac output. In addition, the Ang-II-induced elevations in cardiac output were not altered by alpha adrenoceptor blockade. Therefore, catecholamines do not play a role in mediating the Ang-II effects. The results of this study support the conclusion that Ang-II is capable of increasing cardiac output by constriction of venous smooth muscle. PMID- 1760896 TI - Hormonal correlates of weight loss associated with blood pressure reduction. AB - This study investigated changes in plasma norepinephrine and the renin angiotensin-aldosterone system during weight loss. Subjects were maintained on a hypocaloric and low sodium diet for 12 weeks. During weight loss statistically significant decreases in blood pressure, aldosterone, plasma renin activity, and norepinephrine were evident. Plasma renin substrate was suppressed from week one to eight and returned to control levels by week twelve. The data indicate that a reduction in the activity of the renin-angiotensin-aldosterone system, modulated by circulating norepinephrine and plasma renin substrate, may significantly contribute to the fall in blood pressure associated with weight loss. PMID- 1760897 TI - Interactive video: state of the art. PMID- 1760898 TI - The treatment of hypertension in pregnancy. Clinical pharmacokinetic considerations. PMID- 1760899 TI - Clinical pharmacokinetics of carboplatin. AB - Carboplatin [diammine(1,1-cyclobutanedicarboxylato)platinum(II)] is one of the most promising second generation platinum compounds. Its greater chemical stability in comparison with cisplatin accounts for its lower reactivity with nucleophilic sites of DNA, and may therefore be related to the higher dose necessary to obtain an antitumour effect similar to that of cisplatin. The lower reactivity with proteins may be related to the observed reduction in nephrotoxicity. Its dose-limiting toxicity is myelosuppression, especially thrombocytopenia. Total and ultrafilterable platinum are detected by flameless atomic absorption spectrophotometry, and high performance liquid chromatography with either UV or electrochemical detection is used for the quantification of carboplatin. These 3 species have been measured as a function of time in biological fluids and tissues to determine their pharmacokinetics. Carboplatin has high stability in infusion fluids in the absence of chloride, but it is less stable in plasma and urine. Protein binding is limited, while the low uptake in red blood cells appears to be species dependent. Commonly, carboplatin is administered intravenously, and its pharmacokinetics are linear up to a dose of 2400 mg/m2. In comparison with cisplatin, carboplatin has longer half-lives of ultrafilterable platinum (23 and 120 min versus 6 and 36 min for distribution and initial elimination half-lives, respectively) and a higher cumulative urinary platinum excretion (77 versus 28% of the dose in 24 h), both due to the lower protein binding of carboplatin. The terminal half-life of total platinum is comparable between the 2 compounds (5.8 versus 5.4 days). This value most probably represents the breakdown of proteins to which both compounds are irreversibly bound. Relationships between pharmacokinetics (area under the curve) and pharmacodynamics (extent of myelosuppression or extent of existing kidney failure) have allowed the development of equations for rational dosage reduction. Intraperitoneal administration has been used in cases of residual ovarian cancer: as a result of its higher hydrophilicity and higher molecular weight, carboplatin is cleared more slowly from the peritoneal cavity than cisplatin (6 vs 15 ml/min). The low bioavailability (4 to 12%) and the gastrointestinal side effects observed did not warrant further studies with oral administration. In contrast to results from animal studies, the modulation of carboplatin-induced myelosuppression by diethyldithiocarbamate (DDTC) was not clinically successful. Valuable alternatives may be the combination with WR2721 or colony-stimulating factors. PMID- 1760900 TI - Interleukins. Clinical pharmacokinetics and practical implications. AB - Interleukins and tumour necrosis factor (TNF) are a complex group of proteins and glycoproteins able to exert pleiotropic effects with respect to a number of different target cells. In physiological conditions, they are induced and released in basal amounts only in restricted microenvironments where they have paracrine activity. Any small amounts reaching the circulation do not disturb homoeostasis. During therapy, particularly when these cytokines are administered via conventional routes, it has become apparent that their presence in nonphysiological plasma concentrations and their unselective action cause toxic effects with small benefits. The pharmacokinetics of interleukins-1, -2, -3 and 6 and TNF have been evaluated, and their disappearance from plasma after intravenous administration is very rapid (i.e. the distribution half-life is measured in minutes; the elimination half-life is several hours). The efficiency of catabolic pathways such as renal filtration and/or liver uptake is interpreted as a salutary mechanism for extracting proteins that should not be in the circulation. However, because these cytokines are very potent immunomodulatory agents there is a need to improve their therapeutic index, and to this end a number of possible formulations and routes of administration are now available and may eventually be of practical use. PMID- 1760902 TI - Pharmacokinetic optimisation of oral hypoglycaemic therapy. AB - Two main classes of oral hypoglycaemic drugs, the sulphonylureas and the biguanides, are currently used in the therapy of type II, non-insulin-dependent diabetes mellitus (NIDDM). The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment. Both first- and second generation sulphonylureas are rapidly absorbed from the gastrointestinal tract. In the plasma compartment, these drugs are strongly bound to serum proteins. All sulphonylureas are metabolised in the liver, and the metabolites and the parent drugs are eliminated mainly in the urine, but also (second-generation derivatives) in the faces. Rapid- and short-acting sulphonylureas may improve early insulin release and promote better postprandial glucose control. Long acting derivatives may ensure better control of overnight glycaemia. The elderly are at risk of developing severe sulphonylurea-induced hypoglycaemia, and in this population the agent chosen should have a short or intermediate duration of action and no active metabolites. Caution is needed when prescribing any sulphonylurea in patients receiving drugs known to affect sulphonylurea action, and in those with impaired liver and/or kidney function. The bioavailability of the biguanides ranges from 40 to 60%. Binding to plasma proteins is absent or very low. Metformin and buformin are not metabolised and are excreted in the urine; phenformin undergoes hepatic hydroxylation and is excreted in both urine and faeces. Metformin is the only agent of this class currently recommended for clinical use. The main indications of metformin treatment are NIDDM associated with obesity and/or hyperlipidaemia, and in combination with sulphonylurea both as primary treatment and when secondary failure occurs with sulphonylurea alone. Lactic acidosis may develop in patients receiving therapy with biguanides, especially in the presence of a preexisting contraindication to their use. PMID- 1760901 TI - Pharmacokinetic drug interactions in anaesthetic practice. AB - Patients receive on average 10 different drugs while in hospital; when fewer than 6 are administered the probability of an adverse drug interaction is about 5%, but when more than 15 are given the probability increases to over 40%. Patients presenting for anaesthesia and surgery are likely to receive multiple preoperative drug therapy and also many perioperative medications as part of their anaesthetic regimen. Thus, there is a considerable potential for interactions to occur in anaesthetic practice. Pharmacokinetic interactions occur when the administration of 1 drug alters the disposition of another, and hence alters the concentration of drug at the receptor site, leading to altered drug response. These changes in drug concentration at the receptor site may be produced by alteration of (a) drug absorption and uptake into the body, (b) drug distribution, (c) drug metabolism and (d) drug elimination or excretion by nonmetabolic routes. Interactions affecting the absorption of orally administered medications are often due to the indirect effect of 1 drug on gastric motility and emptying, which leads to reduced, delayed or variable systemic drug availability. Gastric emptying time before elective surgery is normal, but premedication with morphine, pethidine (meperidine) and anticholinergics all delay gastric emptying and hence drug absorption. Inhalational anaesthesia of short duration does not appear to affect drug absorption, although halothane anaesthetic used for longer periods produces a slight delay in gastric emptying. Volatile anaesthetics have been shown to delay the intramuscular absorption of ketamine. Anaesthetic agents may affect drug distribution, and peak concentrations of propranolol, for example, are 4 times higher during halothane anaesthesia in dogs, accompanied by a marked decrease in volume of distribution. This effect has been noted for other drugs, including thiopental and verapamil. Volatile anaesthetics also affect plasma protein binding, leading to displacement interactions in some cases. Volatile anaesthetics affect the metabolism of concomitantly administered drug (a) by altering the rate of delivery to the organ of clearance (e.g. decreasing hepatic blood flow) and (b) by altering the activity of drug metabolising enzymes. It is now well recognised that all the volatile anaesthetics currently in use inhibit the metabolism of a large variety of drugs, e.g. propranolol, lidocaine (lignocaine), fentanyl and pethidine. Other examples of interactions of clinical importance to anaesthesiologists include those between cimetidine and the local anaesthetics and benzodiazepines; inhibition of plasma cholinesterase by drugs such as ecothiopate; interactions between monoamine oxidase inhibitors and sympathomimetics or pethidine and between monoamine oxidase inhibitors and sympathomimetics or pethidine and between isoniazid and enflurane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1760903 TI - Contrast-enhanced MRI for the staging of bronchogenic carcinoma: comparison with CT and histopathologic staging--preliminary results. AB - Nineteen patients with potentially operable bronchial carcinoma were included in a prospective study to assess the staging capabilities of plain and contrast enhanced magnetic resonance imaging (MRI) in comparison with computed tomography (CT) and to compare the results to post-operative histopathological staging (HS). The evaluation focused on the following T-staging criteria: (i) direct invasion of the pleura; (ii) neoplastic invasion of the mediastinum; (iii) differentiation of the primary tumour from alterations of the surrounding lung parenchyma such as inflammation or atelectasis; and (iv) intrathoracic lymph node involvement by tumour. MRI and CT produced similar results for pleural invasion (sensitivity of 0.4 and 0.75 respectively and a specificity of 0.86 and 0.93 respectively). Mediastinal invasion was overdiagnosed in four patients (no false negatives), whereas CT had only one false positive result (two false negatives). Our results showed CT to be superior to MRI for the preoperative evaluation of patients suffering from bronchogenic carcinoma. PMID- 1760904 TI - Chronic lung fibrosis following carmustine (BCNU) chemotherapy: radiological features. AB - Carmustine (BCNU) is a cytotoxic drug which is a recognized cause of acute pulmonary fibrosis. We describe the radiological findings in six patients who received carmustine in childhood for treatment of central nervous system tumours and were subsequently found to have pulmonary fibrosis 13-17 years after treatment. Patients were studied by chest radiography and high resolution computed tomography. The pattern of disease is novel, involving the upper zones in a predominantly peripheral pattern. PMID- 1760905 TI - Tumours involving the intrathoracic vagus and phrenic nerves demonstrated by computed tomography: anatomical features. AB - Four cases of mediastinal tumours involving the intrathoracic vagus and phrenic nerves are presented and their computed tomographic (CT) features are described with particular attention to the intrathoracic course of these nerves. One case of mediastinal plexiform neurofibromatosis appeared as a series of low attenuation masses along the intrathoracic course of the nerves. Three examples of neurilemmomas of the vagus nerve appeared as masses with central low attenuation; one in the retrocaval area, one to the left of the aortic arch, and one in the right paraoesophageal area. Familiarity with the CT anatomy of the vagus and phrenic nerves will greatly assist in the diagnosis of mediastinal tumours. PMID- 1760906 TI - Sonographic findings in tuberculous peritonitis of wet-ascitic type. AB - Sonograms in 46 patients with tuberculous peritonitis of the wet-ascitic type were analysed retrospectively. The ascites was clear in 24 patients (52%). There were fixed membranes, septa and debris in eight patients (17%), floating debris in six patients (13%), mobile strands or membranes in four patients (9%), and fixed septa in four patients (9%). The patients were divided into two groups depending on the amount of ascites: small amount of ascites with clear fluid in eight patients (17%), and moderate or large amount of ascites with clear or complex fluid in 38 patients (83%). Associated findings were omental 'cake' (26%), hepatomegaly (24%), thickened mesentery with adherent small bowel loop (22%), splenomegaly (20%), pleural effusion (17%), lymphadenopathy (13%), and thickening of the ileal wall (7%). The sonographic findings are not specific for tuberculous peritonitis, but may give valuable information to prevent unnecessary laparotomy. PMID- 1760907 TI - Barium meal or endoscopy? A prospective randomized study of patient preference and physician decision making. AB - This study examines the preference of 64 out-patients for either a barium meal or an upper gastrointestinal endoscopy. The sequence of the examinations was randomized to avoid order bias. An initial preference for a barium meal of almost two-to-one, with 53% having no preference, was changed after the investigations to a preference for endoscopy of two-to-one with 5% having no preference. The use of mild sedation and the skill of the endoscopist had a major impact on the patients' opinion of the endoscopic procedure, and on their choice of examination for any repeat study. There was little agreement between clinical diagnosis and the result of investigation, but clinicians tended to accept the reported result of the investigation, especially if the result was abnormal. Despite a change in diagnosis in 34 of 49 patients there was little change in management as a result of the investigations, supporting the view that young patients with dyspepsia may be managed with symptomatic treatment initially, and without investigation. This study lends further support to the view that endoscopy should be the investigation of choice in patients with persistent dyspepsia, especially those whose age or infirmity may make barium examination suboptimal. PMID- 1760908 TI - Double-contrast radiographic features in primary small intestinal lymphoma of the 'western' type: correlation with pathological findings. AB - Eighteen patients with 20 primary lesions of small intestinal lymphoma of the 'Western' type were examined to determine the double-contrast radiographic features of the disease with pathological correlation. The radiographic appearances on double-contrast study were divided into five groups: polypoid (3 lesions), stricturing (6), non-stricturing (3), aneurysmal (3), and intussusception (5). In the first four groups, ulceration, signs of submucosal tumour, and displacement of adjacent loops were frequent. Two early lesions confined to the submucosal layer were also seen. There was a close association between the radiographic appearance and macroscopic findings of the resected specimens, including the cross section of the tumour, but no correlation with the cell type. These results indicate that the double-contrast study accurately reflects the morphological changes of primary small intestinal lymphoma. PMID- 1760909 TI - Spontaneous intramural haematoma of the oesophagus: appearance on computed tomography. PMID- 1760910 TI - A trial to assess the effectiveness of bowel preparation prior to intravenous urography. AB - A randomized prospective trial was undertaken to compare the relative effectiveness of two commonly used bowel preparations (senna tablets and sodium picosulphate powder) administered to patients before they underwent out-patient intravenous urography. Their 'control' films were compared with plain 'kidneys, ureters, and bladder' (KUB) radiographs of patients who had had no bowel preparation. The results show no significant difference in the degree of faecal shadowing between those receiving a bowel preparation and the unprepared patients. Nor is there any difference between the two laxatives. We conclude that the routine administration of a bowel preparation is unlikely to improve the diagnostic quality of out-patient intravenous urograms. In addition, 40% of the urogram patients found the effects of the laxatives to be unpleasant or very unpleasant. PMID- 1760911 TI - The use of a computerized image transfer system linking a regional neuroradiology centre to its district hospitals. AB - We describe a new personal computer based image transfer and storage system. We prospectively assessed the uses and benefits of ImLink (Electronic Imaging Ltd.) in a regional neuroradiology department linked by the system to six referring district general hospitals. One hundred and fifty consecutive CT scans transferred by the system were analysed (142 head, four spine and four body scans). Sixty-eight CT scans were of acute neurosurgical cases. A significant change in management occurred in 55 of these cases (81%), principally as a result of prevention of transfer of head-injured patients when no neurosurgically correctable lesion was evident. The high quality of transferred images achieved by the system allows the provision of specialist radiological advice to colleagues in linked district hospitals. A further 50 non-acute head CT scans were transferred by district hospital radiologists seeking the second opinion of a neuroradiologist. Twenty-three out-of-hours acute head CT scans were transferred from clinicians in our own hospital to the home of the on-call neuroradiologist. Overall 63% of the 150 scans were transferred during normal working hours. We discuss the multiple uses and future potential for such an image transfer and storage system. PMID- 1760912 TI - Technical report: wire guided sialography. AB - An improved technique for performing sialography in difficult cases is described. This is based on the passage of a cannula into the salivary duct ostium over a thin, flexible, blunt guide-wire. PMID- 1760913 TI - Technical report: oxygen saturation monitoring during sedation for chemonucleolysis. AB - Pulse oximetry is widely used during anaesthetic practice to monitor heart rate and oxygenation and has been recommended as a monitor when sedative techniques are used. We monitored 25 patients receiving sedation for chemonucleolysis and showed that 17 became hypoxaemic at some stage of the procedure, none of whom had clinically detectable signs of respiratory depression. We recommend that monitoring with pulse oximetry is used in all patients receiving sedation for radiological procedures and that all radiologists administering sedation be trained in airway management. PMID- 1760914 TI - Case report: hepatobronchial fistula complicating amoebiasis, treated by percutaneous catheter drainage. AB - We report the case of a 41-year-old man who presented with hepatic amoebiasis 18 months after visiting the Far East. His progress was initially complicated by a bronchohepatic fistula which was further complicated by secondary bacterial infection. The fistula persisted and only resolved following percutaneous catheter drainage, thereby avoiding open surgery. PMID- 1760915 TI - Case report: gastroduodenal intussusception--an unusual cause of pancreatitis. AB - Gastroduodenal intussusception is a rare complication of polypoidal gastric tumours, and it has not previously been described as a cause of acute pancreatitis. We report a case of an endoscopically, radiologically and histologically proven intussuscepting gastric leiomyoma presenting with biochemical evidence of acute pancreatitis. The radiological appearance is illustrated and possible mechanisms for the pancreatitis are discussed. PMID- 1760916 TI - Case report: painless thoracic scoliosis due to dumb-bell ganglioneuroma--CT and MRI appearances. PMID- 1760917 TI - MRI of the spine. PMID- 1760918 TI - Persistent colonic spasm. PMID- 1760919 TI - Plasma osmolarity, iodine concentration and urographic images. PMID- 1760920 TI - Measurement systems calibration: microcomputer implementation. AB - Measurement systems used in the collection and processing of laboratory data must be calibrated periodically to obtain accurate results. Because calibration factors can change over time or may be reset to optimize measurements for specific tests, care must be taken to assure that calibration factors and data are aligned correctly. Users should be able to process current data or re-process older data using appropriate calibration factors. The alignment of calibration factors and data should occur in a simple, automatic and transparent way. This document describes one approach to calibration procedures and computer programs used to collect, process, document, measure and display laboratory data. The examples are from our neurophysiology laboratory, where investigators study the mammalian spinal cord and peripheral neuromuscular system. Typical calibration problems, some workable solutions, and computer programs (described in pseudocode) are presented. PMID- 1760921 TI - An image-processing system, motion analysis oriented (IPS-100), applied to microscopy. AB - This paper describes a real-time video image processing system, suitable for image analysis of stationary and moving images. It consists of a high-quality microscope, a general-purpose personal computer, a commercially available image processing hardware module plugged into the computer bus, a b/w TV-camera, video monitors and a software package. The structure and the capability of this system are explained. The software is menu-driven and performs real-time image enhancements, real-time mathematical and morphological filters, image segmentation and labelling, real-time identification of moving objects, and real time analysis of their movements. The program is available in listing form. PMID- 1760922 TI - MRATE: a Pascal program for on-line calculation of metabolic rate using wet gases. AB - MRATE is a Pascal program designed for on-line calculation of metabolic rate in an open circuit system, when outlet gases are not dried. Voltages from O2 and CO2 analysers, humidity and temperature probes and mass flow meter are digitised and used to calculate outlet flow, oxygen consumption, carbon dioxide production, respiratory quotient and metabolic rate. The program may be easily modified to suit a variety of experimental set-ups. PMID- 1760923 TI - A microcomputer-based interactive cough sound analysis system. AB - The occurrence and nature of cough sounds, especially those occurring in asthma in young children, is of considerable interest to workers in paediatrics and general practice. To facilitate our research into the characteristics of such sounds, we have developed a microcomputer-based analysis system, which we call COFF. In this paper we discuss the design and implementation of the system, emphasising its user-friendly, interactive features, and the manner in which it efficiently manages the large amounts of data that research into sounds incurs. We illustrate the operation of the system with examples of spectrograms computed from cough sounds recorded simultaneously at the mouth and through the chest wall. PMID- 1760924 TI - A microcomputer system for collecting and processing physiological information about the masticatory system. AB - A software system has been written for IBM PC, XT, AT and compatible computers to be used for data collection, analysis and display. The system supports the sampling and processing of data for jaw movement tracks, myoelectrical activities of masticatory muscles, the temporomandibular joint (TMJ) and occlusal sounds and bite force, etc. The package includes the following functions: calculating displacement, velocity, curvature, and curvature center of jaw movement trace, analyzing myoelectrical signals in amplitude integration, root mean square and power spectrum, processing TMJ sounds and occlusal sounds and bite force, analysing jaw movement traces and myoelectrical activities during mastication simultaneously, determining the maxillomandibular relations, etc. The program also provides versatile formatting capability for video, printing and plotting of data, and graph creation. The most of the above programs have flexibility and adaptability to other physiological signal processes. PMID- 1760925 TI - RECPAM: a computer program for recursive partition and amalgamation for survival data and other situations frequently occurring in biostatistics. III. Classification according to a multivariate construct. Application to data on Haemophilus influenzae type b meningitis. AB - The methodology of RECursive Partition and AMalgamation (RECPAM) previously presented in Parts I and II (A. Ciampi et al., Computer. Methods Progr. Biomed. 26 (1988) 239-256 and 30 (1989) 283-296) pursues its development with an application to predict long-term effects of a disease given a set of clinical information measured at the time of illness. This paper illustrates how RECPAM deals with a situation typical in Medical Informatics applied to data on Haemophilus influenzae type b meningitis. PMID- 1760926 TI - MACSPEC--a software system for fully automatic processing and analysis of large series of NMR spectra. AB - In vivo NMR spectroscopy often accumulates a large number of spectra (typically 100 individual files or even more) to follow metabolic changes with high time resolution. The analysis of these spectra is very time-consuming for the spectroscopist and, furthermore, it requires the spectrometer's computer, needed for control of experiments. Here we report the software system MACSPEC developed for automatic processing and analysis of large series of individual NMR spectra on a peripheral personal computer. With this software the spectrometer's computer is kept available for experiments, and the necessary interaction of the spectroscopist is limited to a definition of the processing conditions at the beginning of the data analysis. PMID- 1760927 TI - Clinical use of tumor markers in oncology. AB - The perfect tumor marker would be one that was produced solely by a tumor and secreted in measurable amounts into body fluids, it should be present only in the presence of cancer, it should identify cancer before it has spread beyond a localized site (i.e., be useful in screening), its quantitative amount in bodily fluids should reflect the bulk of tumor, and the level of the marker should reflect responses to treatment and progressive disease. Unfortunately, no such marker currently exists, although a number of useful but imperfect markers are available. The predominant contemporary markers are discussed here by chemical class, as follows: glycoprotein markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and prostate specific antigen (PSA); mucinous glycoproteins, including CA 15-3, CA 19 9, mucinous-like cancer antigen and associated antigens, and CA 125; enzymes, including prostatic acid phosphatase (PAP), neuron specific enolase (NSE), lactic acid dehydrogenase (LDH), and placental alkaline phosphatase (PLAP); hormones and related endocrine molecules, including calcitonin, thyroglobulin, and catecholamines; and, molecules of the immune system, including immunoglobulins and beta-2-microglobulin. The biologic properties of each group of tumor markers are discussed, along with our assessment of their role in clinical medicine today. PMID- 1760928 TI - Mitochondrial protein import. AB - A dynamic picture of the mitochondrial protein import pathway is emerging, with conformational alteration a critical feature both preceding and following membrane translocation. The mediators of these steps of conformational alteration, as well as steps of recognition, translocation, and proteolytic cleavage, appear to be proteins. Using powerful tools of genetics and biochemistry, in years to come it should be possible to determine the precise molecular function of these proteins in mediating these novel reactions. PMID- 1760929 TI - Transport of membrane proteins to the cell surface. PMID- 1760930 TI - Protein sorting in polarized epithelial cells. PMID- 1760931 TI - Protein localization and virus assembly at intracellular membranes. PMID- 1760932 TI - Condom conundrums: Part II. PMID- 1760933 TI - A dermatologic diary. Portrait of a practice. PMID- 1760934 TI - Cat scratch disease. PMID- 1760935 TI - Chronic tophaceous gout with severely deforming arthritis: a case report with emphasis on histopathologic considerations. AB - The dramatic clinical presentation of a patient with severe deforming arthritis secondary to chronic tophaceous gout is described. Polarization microscopic examination and use of the De Galantha stain identified the dermal amorphous material as urate crystals. When the possibility of gout is entertained and a lesional biopsy specimen is examined to confirm the diagnosis, it is useful to fix the fresh tissue in absolute ethanol and process the specimen using an anhydrous technique to preserve the crystals. PMID- 1760936 TI - Digitate dermatosis. AB - Two cases of digitate dermatosis are presented. The clinical and histopathologic features of this unique entity are reviewed. We suspect that digitate dermatosis may be more prevalent than reported. PMID- 1760937 TI - Cutaneous involvement in Wegener's granulomatosis. AB - A case of Wegener's granulomatosis is presented. The major features of the disease, with special emphasis on the cutaneous findings, are reviewed. PMID- 1760938 TI - Evaluation of BRL 42715, a beta-lactamase-inhibiting penem. AB - BRL 42715 is a new penem which inhibits a wide range of plasmid as well as chromosomally mediated bacterial beta-lactamases. We used a total of 902 recent clinical isolates, consisting of 455 Enterobacteriaceae, 247 staphylococci and 200 other gram-negative bacteria to evaluate its ability for potentiation of amoxycillin. MICs for all the 104 strains of methicillin-susceptible Staphylococcus aureus were reduced from 8-greater than 32.0 to less than or equal to 0.06 micrograms/ml in the presence of 1-5 micrograms/ml of this penem. It was also highly effective in inhibiting the beta-lactamase of a wide variety of gram negative bacteria, thereby bringing their MIC values for amoxycillin from a 'resistant' range (greater than 32.0 micrograms/ml) to a 'susceptible' range (less than or equal to 8.0 micrograms/ml). Commonly resistant bacteria like Klebsiella, Enterobacter, Citrobacter, Morganella, Serratia, Acinetobacter and Aeromonas were rendered susceptible to amoxycillin in the presence of 1.0-5.0 micrograms/ml of BRL 42715. PMID- 1760939 TI - Imipenem resistance in Acinetobacter baumanii is due to altered penicillin binding proteins. AB - The comparison of a clinical Acinetobacter baumanii isolate (strain No. 4852/88) and its selected imipenem-resistant (IMR) clone exhibited a complex reorganization of the penicillin-binding proteins (PBPs) with diminished labelling of all PBPs except the 24-kD PBP which showed an increased binding of 14C-penicillin. This protein could not be saturated by preincubation of membranes with imipenem at 8-fold the MIC of imipenem, thus indicating PBP alterations responsible for imipenem resistance. In A. baumanii 4852/88 seven PBPs with the apparent molecular weights of 94, 84, 65, 61, 48, 40 and 24 kD could be detected. beta-Lactamase production was barely detectable in any case and could not be enhanced in the presence of various beta-lactams as the inducer. The outer membrane proteins were found identical in both the wild-type strain and the Im clone. So far, imipenem-resistant A. baumanii isolates have been isolated twice in our diagnostic laboratory; however, no implications on the future relevance of the above findings can be made. PMID- 1760940 TI - Comparative antibacterial activity of the penem ALP 201. AB - The minimum inhibitory concentration (MIC) of the new penem ALP 201 was tested against 243 recent clinical isolates of which 95 were from the family Enterobacteriaceae, 50 were from the genus Streptococcus, 50 were Staphylococcus aureus and 48 were Staphylococcus epidermidis. An agar dilution technique was used to determine the MIC50 and MIC90 of ALP 201 in comparison with cefotaxime, cefuroxime, clindamycin, imipenem, piperacillin, tobramycin and vancomycin. Overnight cultures were suspended to produce inocula of 10(5) colonies from a replicator. ALP 201 was shown to have an activity similar to imipenem against most species; ALP 201 was less active than imipenem against Serratia spp. and was more active against S. epidermidis. beta-Lactamase production did not affect the activity of ALP 201. All the other compounds tested were less active than ALP 201 and imipenem. PMID- 1760941 TI - Postantibiotic effect of ciprofloxacin compared with that of five other quinolones. AB - The antimicrobial activity (minimal inhibitory concentration, MIC, and killing kinetics) and postantibiotic effect (PAE) of different concentrations (MIC and 6 mg/1) of ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, fleroxacin and lomefloxacin on pure cultures of Staphylococcus aureus and Escherichia coli were compared in vitro. The MIC, killing kinetics and PAE were determined by standard methods. Ciprofloxacin displayed the lowest MICs, while the highest were those of norfloxacin against S. aureus and lomefloxacin against E. coli. The killing curves showed ciprofloxacin to be the most and norfloxacin the least active. The bactericidal power was dependent on the concentration. At MIC, the fluoroquinolones, with the exception of norfloxacin, induced PAEs of 1-2 h. The effect was, in all cases, greater against E. coli. When assayed at 6 mg/l the PAEs were increased to 2-5 h, the best results being obtained by ciprofloxacin followed by ofloxacin. Norfloxacin produced no PAE on S. aureus and scarcely reached 1.3 h against E. coli. There was a close relationship between bactericidal power and PAE. PMID- 1760942 TI - Virulence of clinical and fecal isolates of Clostridium perfringens type A for outbred NMRI mice. AB - Twelve clinical and 102 fecal isolates from healthy carriers of Clostridium perfringens type A were tested for virulence in juvenile, outbred NMRI mice (intramuscular route). There were marked differences (up to 1,000-fold) in virulence among strains of both groups of isolates. On average, clinical isolates were not more virulent than fecal isolates. Fresh epinephrine (10 micrograms/mouse and given concurrently with bacterial inocula) significantly augmented virulence. The murine model of Hill and Osterhout for experimental gas gangrene yielded reproducible results. Myelosuppressed (cyclophosphamide pretreated) mice were somewhat more susceptible to C. perfringens as contrasted with mice that had been pretreated with either carrageenan type II or with zymosan. The murine virulence of C. perfringens was enhanced significantly by Escherichia coli. PMID- 1760943 TI - Daunorubicin impairs 1-beta-D-arabinofuranosylcytosine uptake. AB - Daunorubicin (DNR) and 1-beta-D-arabinofuranosylcytosine (Ara-C) act in a schedule-dependent fashion on leukemic cells. The present study was undertaken to determine whether the inhibition exerted by DNR on Ara-C cytotoxicity on HL 60 cells could be accounted for by an impairment of its uptake. After 250 ng/ml DNR treatment for 30 min, the time course of Ara-C uptake was measured, up to 128 min of incubation at 37 degrees C and at 4 degrees C, compared with controls. We found that DNR inhibits Ara-C uptake both at 37 and 4 degrees C, mostly acting on passive diffusion. PMID- 1760944 TI - Effects of recombinant human cytokines on cytarabine activity in K562 human myeloid leukaemia cells. AB - The K562 cell line provides a unique population of primitive human myeloid leukaemia cells which can be induced to differentiate along the erythroid, granulocytic, macrophage and megakaryocytic lineages in response to several agents. Cytarabine is not only the most widely used drug in the treatment of myeloid leukaemia but also the most effective agent in K562 cells. The effects of five recombinant human cytokines - interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha, interferon-beta and interferon-gamma on cytarabine-induced growth inhibition and differentiation of K562 cells was studied in liquid suspension cultures. GM-CSF and to a lesser extent IL-3 enhanced the antiproliferative effect of cytarabine in K562 cells, whereas the three interferons reduced it. The efficacy of cytarabine in inhibiting the growth of K562 cells was doubled by its combination with GM-CSF or IL-3 but was halved by its combination with interferons. The five cytokines did not significantly affect cytarabine-induced erythroid differentiation of K562 cells. The present results appear to favour the use of GM-CSF and IL-3 but not of interferons in future treatment strategies based on a combined cytokine and chemotherapy approach for myeloid leukaemia. PMID- 1760945 TI - Oral chemotherapy with idarubicin plus cyclophosphamide in advanced breast cancer. AB - An oral chemotherapy schedule based on idarubicin and cyclophosphamide was evaluated in 31 advanced breast cancer patients. Out of 27 patients evaluable for response, 1 (3.7%) achieved a complete response and 5 (18.5%) a partial response, with an objective response rate of 22.2% (95% confidence limits 8.6-42.3%). The median time to progression was 7 months (range 3-12). Fourteen patients (51.9%) showed a disease stabilization, and 7 progressed (25.9%). Toxicity was mild. Considering the low response rate, but also the advantages of oral chemotherapy and the mild toxicity observed, oral idarubicin plus cyclophosphamide can be considered as a second-choice regimen in advanced breast cancer. PMID- 1760946 TI - [Interprofessional cooperation in surgical medicine. When does the busy surgeon have time to reflect on his own problems? Thoughts during handwashing]. PMID- 1760947 TI - [Evaluation of 17 years' performance as surgical staff physician]. PMID- 1760948 TI - [Comments by a review expert of the North Wurttenberg health insurance organization for surgical claims]. PMID- 1760949 TI - [Hematogenous liver metastases--human pathologic principles]. PMID- 1760950 TI - [Diagnosis and spontaneous course of liver metastases]. PMID- 1760951 TI - [Surgical possibilities and therapeutic chances in liver metastases]. PMID- 1760952 TI - [Helicobacter pylori colonization in surgical patients]. AB - The prevalence of Helicobacter pylori (HP) was examined in 387 patients undergoing endoscopy of the upper gastrointestinal tract. Of central interest was the question to which extent surgical intervention influences the colonisation of the gastric mucosa with HP. The bacillic status was appraised using double microbiological examinations, histological determination and the CLO-test. In 229 patients a 13C-urea-breath test was also carried out (sensitivity 98%). HP could be detected in 90% of all patients presenting with duodenal ulcers as well as in 70% of patients with gastric ulcers, whereas in those patients in whom a lesion of the upper gastrointestinal tract could be excluded through endoscopy. HP was found in only 27%. The prevalence of HP did not increase with age. In patients having undergone distal gastric resection due to gastric ulcers, HP was only rarely found (19%) in the mucosa in the vicinity of the anastomosis following removal of the apparently pathogenetically important antrum mucosa. There was no association between anastomosis ulcers and bacillic colonisation. Following selective proximal vagotomy in patients with duodenal ulcers, HP was found in 80% of all cases. In these patients there was also no association between recurrent ulceration and a HP-positive status. Our results describe the postoperative HP status after different surgical procedures of ulcer therapy: whereas a distal gastric resection removes the antrum mucosa, which provides the necessary environmental milieu, the HP-colonisation rate after selective proximal vagotomy is similar to that in non-operated ulcer disease. PMID- 1760953 TI - [Spontaneous uni- and bilateral Achilles tendon rupture--a frequent complication after kidney transplantation]. AB - In our clinic we observed uni- or bilateral ruptures of the Achilles tendon as a complication in 5% of all renal transplant patients. The majority of ruptures took place within the first two months following transplantation in a phase of increasing physical activity. Besides steroid treatment, elevated uric acid and hyperparathyroidism, advanced age at the time of transplantation as well as long duration of chronic hemodialysis must be considered as risk factors. PMID- 1760954 TI - [Ultrasonic diagnosis in suspected acute appendicitis: probable or certain indications for surgery?]. AB - The diagnostic accuracy and the clinical impact of routine ultrasonography performed by 4 surgeons, were prospectively studied in 366 unselected patients admitted for suspected acute appendicitis. Clinical and sonographic findings on admission were correlated with laparotomy findings, pathological outcome and clinical as well as follow-up data. The overall sensitivity, specificity and accuracy of the clinical diagnosis of acute appendicitis were 55.3%, 94.6% and 84.2% respectively (positive predictive value (PPV) 75.8%, negative predictive value (NPV) 87.3%). Ultrasound enabled visualization of the disease in 67 of 85 (prevalence 23.3%) patients with a histologically confirmed acute appendicitis; false positive results were recorded in 7 cases (sensitivity 78.8%, specificity 97.5%, accuracy 93.1%, PPV 90.5%, NPV 93.8%). Ultrasound was particularly useful in patients presenting with equivocal or highly unsuspective signs of acute appendicitis: of 38 patients with an acute appendicitis in this group ultrasonography enabled to make the diagnosis in 26. The combined approach of clinical evaluation and routine ultrasonography markedly improved the diagnostic accuracy (sensitivity 85.9%, specificity 96.4%, accuracy 94%) and substantially reduced the negative laparotomy rate (7.9%) in patients with suspected acute appendicitis. It is concluded, that ultrasonographic evaluation of the patient with suspected acute appendicitis performed by surgeons is of great assistance in surgical practice. PMID- 1760955 TI - [Esophageal cancer in myasthenia]. PMID- 1760956 TI - [Therapy of spontaneous esophageal perforation]. PMID- 1760957 TI - [Congenital intrathoracic ectopic gallbladder--a currently unreported developmental disorder. Attempt at a classification of abnormal gallbladder sites]. PMID- 1760958 TI - [An unusual case of Chilaiditi syndrome--hepatodiaphragmatic interposition of a sigma elongatum]. PMID- 1760959 TI - [Kuntscher femoral nailing. A 74-year follow-up]. PMID- 1760960 TI - [Guidelines for allogeneic bone transplantation]. PMID- 1760961 TI - [Comment on the contribution by J. R. Izbicki et al.: Retro- and prospective study of the value of clinical and chemical laboratory data in acute appendicitis]. PMID- 1760962 TI - Hufeland's interest in plant movements. AB - Christoph Wilhelm Hufeland (1762-1836) was one of the eminent physicians at the time of Goethe. When only 21 years old, he followed his father as a medical practitioner in Weimar. In 1793 he became Professor of Medicine at the University of Jena, from where he moved, in 1801, to Berlin as the physician in ordinary to king Friedrich Wilhelm III, council of state, and Professor at the leading hospital, the Charite. Hufeland pioneered in what today would be called public hygiene. Many of his lectures and publications were addressed to the educated laymen. In his most read book, the 'Makrobiotik', he emphasizes the importance of the 24-h periodicity as a basic unit of biological chronometry. In view of this, Hufeland has become a kind of 'patron saint' to modern chronobiologists. PMID- 1760963 TI - A mathematical model for time perception with experimentally obtained subjective time scales for humans and rats. AB - The concept of sensation measurement with the entailing subjective scales is explained. It is shown that linearity between, e.g. sensation halving values and standard values implies that subjective sensation (output) grows as a power function of the physical measure of the stimulus (input). This outcome can be used in the scaling of subjective duration, based on reproduction experiments, i.e., experiments in which the participants are required to reproduce given time intervals, e.g., indicated by noise. It will be shown that what is reproduction for the participant is halving for the experimenter, making it possible to determine the parameters of the power function. The model is confirmed experimentally for humans and rats, the rats having a lower exponent than adults. In a recent experiment it was shown that the reproduced durations differ between female and male observers as well as for different sound intensities. These differences could be attributed to differences in parameter values. An interesting observation is that almost all power functions exhibit a discontinuity, possibly indicating a switch between different neural loops as the durations become longer. PMID- 1760964 TI - A chronobiological approach to the effects of cefodizime on monocytic and granulocytic functions of patients with multiple myeloma. PMID- 1760965 TI - Chronobiology meets the need for integration in a reductionist climate of biology and medicine. AB - One of us introduces a chronobiology course to students at the University of Milan, Italy, with a succinct statement that may well serve to summarize the foregoing 24 points. Its few lines distill the preceding details and formulate the raison d'etre of Chronobiology: Chronobiology is: not only a science in its own right; not only a methodology; not only a new kind of statistical analysis; not just an aspect of biology, but a new way of invariably approaching any problem in biology, notably medicine. PMID- 1760966 TI - Spatial frequency of the human short-wavelength-sensitive (blue) cone mechanism. Psychophysical studies and pattern-reversal visual evoked potentials. AB - The interactions of spatial and chromatic processing of the short-wavelength sensitive cone mechanism were studied in humans with patterned (checkerboard) stimuli of various spatial frequency (10, 22, 44, and 85 min of are respectively), under steady exposure to yellow light (575 nm, 390 cd/m2). Psychophysical studies and pattern-reversal visual evoked potentials were employed. Parameters of the transient pattern-reversal visual evoked potentials (pattern reversal rate of 2.4 s-1) especially observed were the latencies of P2 (P100) and N3 and the amplitude of P2-N3. It was only with the largest applicable check size (85 min of arc) that both the psychophysical studies and visual evoked potentials could succeed in satisfactorily isolating the short-wavelength sensitive cone mechanism. Pattern-reversal visual evoked potential latencies are recommended in the evaluation of this cone mechanism because of their smaller variance and higher selectivity in isolating the short-wavelength-sensitive cone mechanism than the amplitude. The peak sensitivity of this cone mechanism was shown to be about 449 nm at the corneal level. The short-wavelength sensitive cone mechanism represented the characteristics of low spatial resolution and long latencies of the pattern-reversal visual evoked potentials. PMID- 1760967 TI - Longitudinal measures in children receiving ENCAD for hereditary retinal degeneration. AB - A hydrolysate of yeast RNA (ENCAD) is used in the Soviet Union for the treatment of hereditary retinal degenerations. We report longitudinal data from three young patients who have made at least two visits to the Soviet Union over a five-year period to receive treatment with ENCAD. Two children were diagnosed with cone-rod degeneration and the third has an isolated (simplex) form of retinitis pigmentosa. Visual function measurements were obtained before and after each visit to Moscow. In the comparison of previsit and postvisit visual acuity, 30 Hz flicker amplitude, and visual fields, ENCAD treatment had no significant short term effect. Despite treatment with ENCAD, each patient has shown a significant decrease in visual function over the 5-year period. The rate of progression in these patients appears similar to previously published data on the natural history of their retinal degenerative disorders. PMID- 1760968 TI - Color pattern-reversal visual evoked potential in eyes with ocular hypertension and primary open-angle glaucoma. AB - Color pattern-reversal visual evoked potential testing was performed in 99 normal eyes, 27 eyes with ocular hypertension and 30 eyes with primary open-angle glaucoma with the use of black-white, black-red and black-blue color checkerboard stimuli. The P1 wave peak time and amplitude of the eyes with ocular hypertension and glaucoma were significantly different from those of age-similar normal eyes, especially on the black-red and black-blue checkerboards (p less than 0.001). The differences between the ocular hypertensive and glaucomatous eyes were of less significance. The P1 peak time difference between black-white and black-red checkerboards may serve as an important parameter in the early diagnosis of glaucoma. PMID- 1760969 TI - The effects of age on steady-state pattern electroretinograms and visual evoked potentials. AB - Steady-state pattern-reversal electroretinograms and visual evoked potentials were simultaneously recorded in two groups of young and elderly normal volunteers. The young group consisted of 23 subjects (13 women and 10 men) aged 18 to 28 years, and the elderly group consisted of 24 subjects (11 women and 13 men) aged 58 to 77 years. Stimuli were square-wave gratings ranging in spatial frequency from 0.5 to 6 c/deg and phase reversed at a frequency of 4 Hz. Pattern reversal electroretinograms and visual evoked potentials consisted of a prominent second and a smaller fourth harmonic response. Spatial frequency-amplitude functions of the pattern-reversal electroretinogram second and fourth harmonics were similar for the young and elderly groups. The mean fourth harmonic phase was significantly shifted in elderly subjects compared with young subjects for all spatial frequencies tested. Spatial frequency tuning was observed for amplitude and phase functions of the visual evoked potential second and fourth harmonic responses for both age groups. Age had a significant effect on phase for spatial frequencies above 1.5 c/deg. Amplitude of the fourth harmonic was significantly lower for the elderly group at 1.5-4 c/deg. Phase was significantly different between groups for spatial frequencies below 3 c/deg. Our results suggest that aging influences both retinal and central visual pathways. Aging differentially affected the visual evoked potential second and fourth harmonic responses, suggesting different neuronal origins for these components. PMID- 1760970 TI - Influence of a twofold voluntary hyperventilation on visually evoked cortical potentials and human pupillogram. AB - We studied the direct and aftereffects of twofold hyperventilation (HV) on pattern reversing VEPs and pupillograms (PGs) of 19 healthy volunteers. The VEP N80 and P100 latencies increased during HV. Both peak times were maintained for a longer period, up to 20 minutes after HV-2 ended. In addition, the PG-latency time during HV and the PG-construction time during and after HV were increased. The results indicated a temporary delay of neural afferent transmission in the visual system during and after HV. A similar delay of the nervous transmission appeared in the efferent part of the system regulating the pupillary movements after HV ended. The observed changes of the VEP and PG parameters most probably resulted from the hypocapnia cased by HV and its effect on the brain vessels, although other explanations for the changes of the VEP- and PG-parameters may have been possible. PMID- 1760971 TI - The pattern electroretinogram in retinal and optic nerve disease. A quantitative comparison of the pattern of visual dysfunction. AB - A retrospective analysis was performed on the transient and steady-state pattern electroretinograms recorded from 42 patients with glaucoma, 13 patients with senile dementia of the Alzheimer's type, 58 patients with diabetes mellitus, and 92 control subjects to evaluate the pattern of electroretinographic changes associated with retinal and optic nerve disease. The amplitudes of both the initial positive component (N1 to P1) and the subsequent negative component (P1 to N2) of the transient (4 rps) responses were measured. From these measurements the (P1 to N2)/(N1 to P1) was derived. The N1 to P1 amplitude of the steady-state pattern electroretinogram also was measured. In the glaucoma patients all three amplitude measures, as well as the amplitude ratio of the components of the transient response, were reduced significantly compared with age-matched controls (p less than 0.05). A similar pattern was detected in the patients with Alzheimer's disease, but in this case the only statistically significant amplitude reduction was in the steady-state pattern electroretinogram. A different pattern was observed among the diabetic patients (both with and without retinopathy). Only minor reductions in the amplitude of the transient pattern electroretinogram, which were not statistically significant, were noted. In addition, the ratio of the amplitudes of the components of the transient response did not differ from age-matched controls. The amplitude of the steady-state pattern electroretinogram was reduced in diabetics, but this was significant only for those patients with retinopathy (p less than 0.01). These findings support the suggestion that an analysis of both the positive and negative components of the pattern electroretinogram may be useful for differentiating the contributions of retinal and optic nerve dysfunction to visual impairment. The results also indicate that in both retinal and optic nerve disease the steady-state pattern electroretinogram can be an earlier sign of dysfunction than the transient pattern electroretinogram. PMID- 1760973 TI - Detection of hidden visual loss in multiple sclerosis. A comparison of pattern reversal visual evoked potentials and contrast sensitivity. AB - The detection of hidden visual loss is important in establishing the diagnosis of multiple sclerosis, especially in patients who have neurologic symptoms of the disease. Both visual evoked potentials and contrast sensitivity have been used for this purpose. We compared the sensitivities of pattern-reversal visual evoked potentials and contrast sensitivity, measured with the Vistech VCTS 6500 chart, in detecting hidden visual loss in 18 patients with multiple sclerosis whose visual acuity was correctable to 20/20 (6/6) or better in the examined eye. Thirteen patients had delayed visual evoked potential latencies. An additional four patients had reduced P100 amplitudes without prolonged latencies. Nine patients had abnormal contrast sensitivity. The visual evoked potential was more sensitive than contrast sensitivity at detecting hidden visual loss in patients with multiple sclerosis (p less than 0.01). PMID- 1760972 TI - Selective reduction of oscillatory potentials and pattern electroretinograms after retinal ganglion cell damage by disease in humans or by kainic acid toxicity in cats. AB - We recorded pattern electroretinograms, scotopic threshold responses, oscillatory potentials and ganzfeld flash electroretinograms in patients with glaucoma or other optic nerve diseases and in cats with inner retinal damage caused by intravitreal injections of kainic acid. In both studies, the scotopic b-wave and the scotopic threshold responses were normal but the oscillatory potentials and pattern electroretinograms were not. The photopic b-wave was also often reduced in patients with scotopic oscillatory potential reduction, and the reduction was proportionate to the oscillatory potential change. Oscillatory potentials were as frequently reduced as pattern electroretinograms in both patient groups, and in the few cases where only one response was reduced, there was no bias toward either measure. In cats, the effects of intravitreal injection of various doses of kainic acid on the retina were evaluated electrophysiologically, and structural damage was assessed histologically. After 25 nmol of kainic acid, the pattern electroretinograms and oscillatory potentials were reduced but neither the b-waves nor the scotopic threshold responses, were affected. Histologic studies of retinas after this dose showed swollen dendrites that were restricted to the outer part (off-sublamina) of the inner plexiform layer. Serial semithin sections indicated that most, if not all, of the swelling was confined to dendrites of large ganglion cells. Our results indicate that the size and sensitivity of the oscillatory potential response may have a role in the diagnosis and management of early glaucoma and optic nerve disease, and that the photopic electroretinogram may give similar information. PMID- 1760974 TI - [Care and rehabilitation of patients without a larynx]. PMID- 1760975 TI - [Rehabilitative nursing--a changing professional concept]. PMID- 1760976 TI - [Rehabilitation instead of taking a cure]. PMID- 1760977 TI - [Rehabilitation-oriented nursing in a hospital]. PMID- 1760978 TI - [Positioning techniques for the prevention of shoulder pain in the early phases of tetraplegia]. PMID- 1760979 TI - [Rehabilitation of patients with neurologic disorders]. PMID- 1760980 TI - [Rehabilitation of patients with cranio-cerebral injuries]. PMID- 1760981 TI - [Rehabilitation of cancer patients from the viewpoint of the social worker]. PMID- 1760982 TI - [Continuing education rehabilitation. Nursing specialty rehabilitation?]. PMID- 1760983 TI - [Long-term care and rehabilitation--a Berlin pilot project]. PMID- 1760984 TI - [Rehabilitation in pediatric nursing. A curriculum for a minor part of pediatric nursing]. PMID- 1760985 TI - [Early rehabilitation: medical, therapeutic and nursing aspects]. PMID- 1760986 TI - [The situation of handicapped adolescents in rehabilitation facilities from a psychotherapeutic point of view]. PMID- 1760987 TI - [Society for the encouragement and support of children with neurologic diseases and their families]. PMID- 1760988 TI - [Education in the nursing professions]. PMID- 1760989 TI - [Memorandum against the new discussion on the non-value of life]. PMID- 1760990 TI - [A light on the horizon of pragmatic recommendations for disinfection]. PMID- 1760991 TI - The human placental lactogen genes: structure, function, evolution and transcriptional regulation. AB - hPL is a member of an evolutionarily related gene family including hGH and hPRL. Expression of hPL is limited to the placenta but its physiological actions are far reaching. hPL has a direct somatotropic effect on fetal tissues, it alters maternal carbohydrate and lipid metabolism to provide for fetal nutrient requirements, and aids in stimulation of mammary cell proliferation. Two hPL genes (hPL3 and hPL4) encoding identical proteins are responsible for the production of up to 1-3 g PL hormone/day. Recent studies have characterized the regulatory controls of hPL expression. At the post transcriptional level, RNA stability may contribute to variable levels of hPL3 vs. hPL4 production. In addition, non-tissue-specific protein-promoter interactions involving the Sp1 transcription factor are necessary for hPL transcription initiation. A transcriptional enhancer located 3' to the hPL3 gene is responsible for the placenta-specific expression of this gene, while an additional enhancer may be located 3' to the hPl4 gene. The hPL enhancer is bound by multiple proteins including at least one placental specific protein that interacts with a TEF-1 motif. Therefore, enhancer-protein interactions most likely play a large part in the high levels of placenta-specific hPL expression. PMID- 1760992 TI - Mammosomatotropes: presence and functions in normal and neoplastic pituitary tissue. PMID- 1760993 TI - Hypoglycemia unawareness. AB - Hypoglycemia unawareness can occur in diabetic as well as nondiabetic individuals. A single causative mechanism for its occurrence is not yet apparent. It is likely to be multifactorial but current evidence favors a major role for some type of CNS adaptation. Certainly in some instances, classic autonomic neuropathy could be a contributory factor in patients with longstanding diabetes. Most, if not all, individuals with this condition have reduced plasma epinephrine and/or norepinephrine responses during mild hypoglycemia. Although it may be difficult to distinguish between mere reductions in the magnitude of a response and a true alteration in the threshold to initiate that response, four studies (44, 59, 65, 86) have provided evidence for an increase in the threshold (greater hypoglycemia required) for activation of counterregulatory hormone secretion associated with reduced awareness of hypoglycemia; in one study (44), diabetic patients had developed abnormalities with improved glycemic control after intensive insulin therapy; in another study (59), diabetic patients had recurrent hypoglycemia but did not differ in glycemic control (as assessed by glycosylated hemoglobin values) from subjects aware of hypoglycemia. In the two other studies, patients with impaired counterregulatory hormone responses and hypoglycemia unawareness had lower glycosylated hemoglobin levels than the other patients (65, 86). Altered tissue sensitivity to catecholamines seems unlikely to provide a primary explanation since not all symptoms are adrenergic and since, as mentioned earlier, most patients with this condition have reduced or delayed catecholamine responses to hypoglycemia, which in themselves could explain reduced awareness of hypoglycemia. Furthermore, patients with diabetic autonomic neuropathy have been reported to have increased sensitivity to catecholamines (143). One frequent observation, dating back to the early descriptions of hypoglycemia unawareness (17-19), is that patients with this condition have had frequent episodes of hypoglycemia. Although it is easy to envision how reduced warning symptoms could result in development of severe hypoglycemia, it is quite possible that frequent episodes of hypoglycemia themselves might initiate the process. For example, as depicted in Fig. 4, episodes of mild hypoglycemia occurring in insulinoma patients, diabetic patients undergoing intensive insulin therapy, or patients with longstanding diabetes complicated by autonomic neuropathy and impaired glucagon secretion could lead to CNS adaptation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1760994 TI - Recurrent secretion of progesterone in large amounts: an endocrine/metabolic disorder unique to young women? PMID- 1760995 TI - Pregnancy and the prolactin family of hormones: coordination of anterior pituitary, uterine, and placental expression. PMID- 1760996 TI - Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins. AB - Human GH represents a family of proteins rather than a single hormone. The circulation contains a bewildering array of GH forms, including several monomeric variants, their homo- and heteropolymers, fragments, and complexes with at least two BPs. The net biological activity of this mixture is difficult to predict, as the various molecular forms interact as partial agonists and/or antagonists at the receptor level. The number of GH forms that can be counted in plasma exceeds 100. Table 5 attempts to illustrate what is known and provide estimates for circulating variants. It does not include GH-V and its variants, which have to be added in pregnancy. Of note, what is commonly understood as "plasma GH," i.e. free monomeric 22K, represents only 21% of total immunoreactivity in plasma. In view of this complicated picture, it should be no surprise that different assays of plasma GH yield different results (107, 108, 290). While immunoassays are relatively unaffected by the BPs (291), receptor assays are seriously affected by the high affinity BP (261). Immunoassays, particularly of the monoclonal variety, are vulnerable to differential recognition of molecular variants depending on the unique epitope specificity of the antibody used. Polyclonal assays are more robust in this regard because of "epitope averaging" among the wide spectrum of epitope specificities present in the antibody population. Future work should aim at developing antibodies that are specific for individual GH variants. Such molecular probes will be helpful not only in standardizing immunoassays, but also in delineating the biological role of the various GH forms. The physiological significance of the numerous GH forms (or of the BPs) is still largely unknown. Progress in this area has been hampered, on the one hand, by the unavailability of pure GH variants in quantities sufficient for biological studies, and, on the other, by a certain lack of interest stemming from suspicions about artifacts. The recent resurgence of interest in GH and in its receptor and BPs should also refocus attention on the various molecular forms. Thus far, this interest has been largely confined to monomeric 22K, which is certainly effective for its original intended purpose, namely growth promotion. Whether 22K is sufficient for optimal growth and development, or whether it can fulfill all the functions of the GH family is unknown. It can be argued that evolutionarily conserved GH variants probably have biological importance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1760997 TI - Effects of dietary trans fatty acids on blood pressure in normotensive subjects. AB - Consumption of essential fatty acids of the (n-6) series may affect blood pressure in man. Trans fatty acids in the diet interfere with the metabolism of essential fatty acids in rats. We therefore measured the effect of dietary trans fatty acids on blood pressure in 25 men and 34 women. Each subject consumed, in random order, three mixed natural diets, each for three weeks. The composition of the three diets was similar, except for 10.4 per cent of energy, which was provided by either oleic acid, trans fatty acids, or saturated fatty acids. The intake from polyunsaturated fatty acids was 3.4 per cent on the saturated-fat diet and 4.6 per cent on the other two diets. On the oleic-acid diet systolic blood pressure was 113 +/- 12.8 mmHg and diastolic blood pressure 66 +/- 8.3 mmHg, on the trans-fatty-acid diet 112 +/- 12.2 mmHg and 67 +/- 8.1 mmHg, and on the saturated-fat diet 112 +/- 12.6 mmHg and 67 +/- 8.1 mmHg. No significant differences were observed in blood pressure levels between the three diets. We conclude that neither trans nor saturated fatty acids influence blood pressure levels in normotensive subjects relative to oleic acid. PMID- 1760998 TI - The effect of dietary energy percentage of fat and its P/S ratio on incorporation of n-3 PUFA and leukotriene production during fish oil supplementation in healthy volunteers. AB - The effect of low (25 per cent of energy) and high (35 per cent of energy) fat diets with either low (less than 0.4) or high (greater than 1.0) polyunsaturated/saturated fatty acid (P/S) ratios on fatty acid compositions of plasma cholesterol esters and neutrophil phospholipids, and leukotriene production was studied in four groups of healthy volunteers supplemented with 6 g fish oil daily for four weeks. Except for three subjects, eicosapentaenoic acid (20:5n-3) content markedly increased from baseline in the plasma cholesterol ester fraction and to a lesser extent in the neutrophil phospholipid fraction. The increase in the plasma cholesterol ester fraction was inversely, though weakly related to the dietary intake of linoleic acid (18:2n-6). At supplementation endpoints, the 20:5n-3/20:4n-6 ratio in both plasma cholesterol esters and neutrophil phospholipids was highest in the groups consuming diets with low P/S ratio. In vitro leukotriene B5 production by neutrophils, did not differ between groups and there was no consistent suppression of LTB4 production in this four-week study. It is suggested that factors other than the actual dietary 18:2n-6 intake additionally influence the accumulation of 20:5n-3 in tissue during dietary fish oil supplementation. PMID- 1760999 TI - Changes in hedonic responses to sweet and fat in recently diagnosed non-insulin dependent diabetic patients during diet therapy. AB - A study was undertaken to find out how the hedonic responses to, and reported liking and consumption of, sweet and fat foods change during the first months of diet therapy of recently diagnosed patients with non-insulin-dependent diabetes mellitus. The patients were 12 women and 19 men aged 40-65 years. The methods used consisted of hedonic rating tests and summated scales which measured overall tendencies to like and consume fatty and sweet foods. These measurements were made three times at intervals of six weeks. At the same time clinical measurements, weight and glycaemic control were recorded. Hedonic ratings of sweet juices decreased during three months of therapy, but hedonic responses to fatty food items (cheese, milk) remained practically unchanged. After three months of diet therapy the diabetic subjects liked fatty and sweet foods less and consumed them less frequently, which was the aim of the diet therapy. At the same time their metabolic control improved markedly, too. PMID- 1761000 TI - Incidence of premature rupture of membranes in pregnant women with low leukocyte levels of vitamin C. AB - The present study was undertaken to explore the association between vitamin C nutritional status in pregnant women with premature rupture of the chorioamniotic membranes (PRM). A case-control cross-sectional study was carried out in 10 women with PRM and 19 women without PRM. The women were evaluated in the first hours postpartum while hospitalized: 10 ml of blood were obtained from each woman to determine vitamin C expressed as micrograms/10(8) leucocytes or microgram/mg of leucocyte protein. Data on fruit and vegetable consumption was collected by a frequency dietary survey and the hospital clinical records were reviewed to obtain their obstetric history and data on the presence of infection during pregnancy, in placenta and/or in fetal membranes. Low vitamin C levels were considered at a cut-off point equal or less than 26.33 micrograms/10(8) leucocytic cells and 3.15 micrograms/mg leucocyte protein. An association was found between low vitamin C levels and cases with PRM. No difference was found in the frequency of consumption of fruit and vegetables between the two groups. Infections were more frequently found in the PRM group, when the women had low levels of vitamin C, and when both risk factors were present simultaneously the proportion of PRM cases identified was greater than 0.75. PMID- 1761001 TI - The reproducibility of the modified relative dose response (MRDR) assay in healthy individuals over time and its comparison with conjunctival impression cytology (CIC). AB - The modified relative dose response (MRDR) assay is a minimally invasive method of detecting marginal vitamin A status. In the present study, the MRDR assay was performed four times in six well-nourished adults and in one male five-year-old child over a seven-month period. In all instances, assay ratios of dehydroretinol (DR) to retinol (R) were less than 0.03, the tentative cutoff value of 'normal' for the MRDR assay in humans. The mean ratio for all time points for all individuals was 0.015 +/- 0.005, with a mean coefficient of variation of 27 +/- 13%. In a related experiment, both MRDR and conjunctival impression cytology (CIC) tests were conducted on nine adults and the same male child. All DR/R ratios were less than or equal to 0.021, and all CIC specimens were normal. Thus, the DR/R ratio in well-nourished individuals, although showing some variation, does not oscillate between abnormal and normal responses. Furthermore, the DR/R ratios and CIC patterns were fully concordant. PMID- 1761002 TI - Temperature and sweating responses in one-legged and two-legged exercise. AB - In looking at the thermoregulatory responses resulting from symmetrical or asymmetrical exercise, this paper has focused on the effect of local skin temperature (Tsk,local) on local sweat rates (msw,local) during one-legged (W1) and two-legged (W2) exercise on an ergocycle. Five subjects underwent four 3-h tests at 36 degrees C, each consisting of six 25-min exercise periods alternating with 5-min rest periods. The subjects performed W1 and W2 at 45 and 90 W, respectively, either dehydrated or rehydrated. Body temperatures and total sweat rate were measured as well as four msw,local (on chest and thighs), assessed from sweat capsules under which Tsk,local was maintained at predetermined levels (37.0 degrees C and 35.5 degrees C). The combinations of Tsk,local levels, capsule locations, exercise intensity and hydration level chosen in our protocol led to the following results. The hydration level affected rectal temperature but not total or msw,local. No specific effect of muscle activity was found; msw,local on thighs of resting and working legs were similar. The msw,local were only influenced by exercise intensity, msw,local being more elevated during the higher intensity. No significant effect of Tsk,local on msw,local was found, whatever the experimental condition and/or the location. It was concluded that local thermal effects on msw,local could have been masked by the strong central drive for sweating which has been found to exist in subjects exercising in a warm environment. PMID- 1761003 TI - Surface electromyogram spectral characterization and motor unit activity during voluntary ramp contraction in men. AB - The relationships were investigated between the surface electromyographic (SEMG) power spectrum analysed by the 20 order autoregressive model (AR spectrum) and underlying motor unit (MU) activity during isometric contractions increasing linearly from 0% to 80% maximal voluntary contraction. Intramuscular spikes and SEMG signals were recorded simultaneously from biceps brachii muscle; the former were analysed by a computer-aided intramuscular MU spike amplitude-frequency (ISAF) histogram and the latter subjected to AR spectral analysis. Results indicated that there was a positive correlation between the force output and the mean amplitude of the ISAF histogram but not with the mean frequency. These changes were accompanied by changes in relative power of the high frequency (100 200 Hz) peak (HL) in the AR spectrum. It was also found that there was a positive correlation between the mean amplitude of the ISAF histogram and the HL value. These data suggested that the power of the high frequency peak in the AR spectrum of the SEMG signal preferentially reflected the progressive recruitment of underlying MU according to their size. Differences between the AR spectrum and the spectrum estimated by fast Fourier transform algorithm have also been discussed. PMID- 1761004 TI - Influence of the bicarbonate pool and on the occurrence of 13CO2 in exhaled air. AB - In 13CO2 breath tests, based on 13C:12C ratio measurements, the appearance of 13C in exhaled CO2 was monitored after the administration of a 13C-labelled compound. Independently of the substrate used, the existence of a bicarbonate pool into which the CO2 produced enters before being exhaled, imposes a delay on the appearance of changes in the 13C:12C ratio. To estimate the nature and magnitude of this delay, we applied a two-compartment model to describe the kinetics of the body bicarbonate pool and we evaluated the 13C:12C ratio of CO2 entering that pool from the measured 13C:12C ratio in the exhaled CO2 after an oral intake of "naturally labelled" 13C-glucose. Our results demonstrated that discrepancies between total and exogenous glucose oxidation in relation to the peak occurrence time, as well as the absolute quantities, could be adequately explained by the interference of the bicarbonate stores. PMID- 1761005 TI - Non-exercise daily energy expenditure and physical activity pattern in male endurance athletes. AB - The present study was performed to determine whether differences in non-exercise daily energy expenditure (Md,ne) exist between trained and untrained individuals. The data from seven cross-country skiers were compared with those from eight sedentary men. Daily energy expenditure (Md) was determined using the heart rate oxygen consumption relationship; resting metabolic rate (Mr) was measured using indirect calorimetry. A physical activity questionnaire and ratios of Md or Md,ne to Mr were used as indices of physical activity. Md and Mr were significantly higher in the trained subjects whereas Md,ne was identical in the two groups. The ratio of Md,ne to Mr and the data from the physical activity questionnaire showed that there was no significant difference in daily energy expenditure and physical activity pattern during the non-exercise time. These results suggest that the exercise-induced increase in daily energy requirements is not compensated by a more sedentary life during the other daily activities in these trained men. PMID- 1761006 TI - Cyclic intramuscular temperature fluctuations in the human forearm during cold water immersion. AB - The purpose of the present study was to investigate the intramuscular temperature fluctuations in the human forearm immersed in water at 15 degrees C. Tissue temperature (Tt) was continuously monitored by a calibrated multicouple probe during 3 h immersion of the forearm. The probe was implanted approximately 90 mm distal from the olecranon process along the ulnar ridge. Tt was measured every 5 mm, from the longitudinal axis of the forearm (determined from computed tomography scanning) to the skin surface. Along with Tt, rectal temperature, skin temperature and heat loss of the forearm were measured during the immersions. Five of the six subjects tested showed evidence of cyclic temperature fluctuations in the forearm limited to the muscle tissue. The first increase of the muscle temperature was observed 75 (SE 6) min after the onset of the immersion, and the duration of the cycle averaged 36 (SE 3) min. The maximum increase of the muscle temperature, which ranged between 0.4 degrees C and 1.0 degrees C, was measured at the axis of the forearm, and was inversely correlated to the circumference of the subject's forearm (P less than 0.05). No corresponding increases of the skin temperature and heat loss of the forearm were observed for the complete duration of the immersion. These data support the hypothesis of a significant contribution of the muscle vessels during cold induced vasodilatation in the forearm. PMID- 1761008 TI - Validity of heart rate and ratings of perceived exertion as indices of exercise intensity in a group of children while swimming. AB - The purpose of this study was to investigate the validity of heart rate (fc) and ratings of perceived exertion (RPE) as indices of exercise intensity in a group of children while swimming. Six healthy male swimmers, aged 10-12, swam tethered using the breast-stroke in a flume. The resistance started at 1.0 kg and increased in 1.0 kg steps up to the point of their exhaustion. The subjects swam for 5 min during each period, with a rest of 10-20 min until they had returned to their resting fc level. The last exercise intensity was with the maximal mass the subjects could support for 2 min. The last min of oxygen consumption (VO2) and 30 s of fc were measured during each exercise period. The subjects gave their RPE assessment at the end of exercise. The individual relationships between fc and VO2, and percentage maximal oxygen consumption (%VO2max) were linear with a high correlation r = 0.962-0.996 and r = 0.962-0.996, respectively. Therefore, it was concluded that fc was valid as an index of the exercise intensity of children while swimming. Compared to the results found in adults using a similar protocol, the children's fc were 8.3-26.9 beats.min-1 higher than those of the adults at the given %VO2max. The present study showed two different patterns in the relationship between VO2 and RPE in individuals. In two subjects the RPE increased linearly with VO2 while in the other four subjects the increase was discontinuous. If fc and RPE were to be applied to the setting and evaluation of exercise intensity during swimming, it would seem that fc would be a more useful guide than RPE for some children. PMID- 1761007 TI - Serum hormones in male strength athletes during intensive short term strength training. AB - Training-induced adaptations in the endocrine system and strength development were investigated in nine male strength athletes during two separate 3-week intensive strength training periods. The overall amount of training in the periods was maintained at the same level. In both cases the training in the first 2 weeks was very intensive: this was followed by a 3rd week when the overall amount of training was greatly decreased. The two training periods differed only in that training period I included one daily session, while during the first 2 weeks of period II the same amount of training was divided between two daily sessions. In general, only slight and statistically insignificant changes occurred during training period I in mean concentrations of serum hormones examined or sex hormone-binding globulin as well as in maximal isometric leg extensor force. However, during training period II after 2 weeks of intensive strength training a significant decrease (P less than 0.05) was observed in serum free testosterone concentration [from 98.4 (SD 24.5) to 83.8 (SD 14.7) pmol.l-1] during the subsequent week of reduced training. No change in the concentration of total testosterone was observed. This training phase was also accompanied by significant increases (P less than 0.05) in serum luteinizing hormone (LH) and cortisol concentrations. After 2 successive days of rest serum free testosterone and LH returned to (P less than 0.05) their basal concentrations. Training period II led also to a significant increase (P less than 0.05) [from 3942 (SD 767) to 4151 (SD 926) N] in maximal force.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761009 TI - Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans. AB - The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure (BPa) decreased by 23%-30% and heart rate (fc) increased but only during NTG infusion (+22%; P less than 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: -26%, P less than 0.01; SNP: -34%, P less than 0.02] and subcutaneous vascular resistance changed only with SNP (-31%, P less than 0.02). After hypotension was discontinued the subcutaneous blood flow decreased ( 13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between fc and BPa (NTG: r = -0.525, P less than 0.01; SNP: r = -0.622, P less than 0.01) as well as with subcutaneous blood flow (NTG: r = -0.653, P less than 0.001; SNP: r = -0.573, P less than 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W.m-1.degree C-1 vs SNP 0.42 (SEM 0.1) W.m 1.degrees C-1, P less than 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P less than 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects. PMID- 1761010 TI - Dietary intervention and training in swimmers. AB - To ascertain if muscle damage occurred in swimmers as a result of high-intensity training and to find if fluid and dietary manipulation could affect muscle damage, we studied 40 members of the University of Florida swimming team using creatine kinase (CK) and lactic dehydrogenase (LDH) as markers of muscle damage during a 6-month period of intensive training. During this time, training intensity, fluid intake during exercise and dietary supplementation were all modified one by one to examine their individual effects. During a control period of 4 weeks, all swimmers drank water before and during (120 min) workouts. CK in men at the end of this period averaged 315, SD 122 (normal less than 170 IU.l-1). Half of the swimmers were then given 500 ml of a glucose-electrolyte solution (GES) (Na 21 mmol.l-1, Cl 13 mmol.l-1, K 2.5 mmol.l-1, PO4 5 mmol.l-1 and glucose 6%) before workouts and twice at intervals during the workout, while half continued to drink the same volume of water. One week after division into fluid groups, the workout intensity was increased by about 10%. Another week later CK had increased to 500, SD 180 IU.l-1 in swimmers drinking water, but fell to 280, SD 105 IU.l-1 in those drinking GES (P less than 0.05). The second phase of the study began after a 4-week control period during which all athletes drank water before and during workouts. The swimmers were divided into four matched groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761011 TI - The electro-mechanical delay of the erector spinae muscle: influence of rate of force development, fatigue and electrode location. AB - Electro-mechanical delay (EMD) values of the erector spinae muscle were obtained using a technique based on the cross-correlation between the force and the electromyogram (EMG). Seven subjects performed a series of 20 submaximal dynamic isometric contractions in a seated position at two frequencies (0.5 Hz and 1 Hz) to study the influence of the rate of force development on EMD. Mean EMD values of 125.7 (SD 28.1) ms (1 Hz) and 136.8 (SD 28.6) ms (0.5 Hz) were shown to differ significantly (P = 0.02). This finding supports the hypothesis that EMD is inversely related to the rate of force development and implies that the time to stretch the series elastic component is an important factor determining EMD. After performing a series of fatiguing contractions EMD did not differ significantly from the control value. Multiple regression analysis showed that maximal voluntary contraction force (MVC) and endurance time of the fatiguing exercise correlated significantly with EMD. The site from which the EMG signal was recorded had no significant influence on EMD. However, the coefficient of correlation between force and the EMG-signal differed significantly between electrode positions. The magnitude of the EMD values found emphasized the need to account for this delay when interpreting temporal patterns of activation of the muscles in, for example, lifting tasks. PMID- 1761012 TI - Effect of phentolamine on the relationship between O2 consumption and delivery in sheep. AB - The oxygen flux challenge test (OFT) has recently been used in critically ill patients as a dynamic test for assessment of the response in oxygen consumption (VO2) to an increase in O2 delivery (QO2). Such a test may indicate whether a patient demonstrates delivery-dependent VO2. However, the increase in whole body VO2 following an increase of QO2 might be due to the agents used for the OFT. In this study, we examined the possibility of obtaining false positive OFT with an alpha-adrenergic antagonist. Five normothermic thiopentone-anaesthetised and mechanically-ventilated (inspired O2 fraction, 0.3; expired CO2 fraction, 0.045 0.055) adult sheep (25-31 kg) were investigated. The QO2 was increased in a stepwise fashion from 200 to 850 ml.min-1 by vasodilatation with intravenous infusion of phentolamine. The VO2 was calculated at each step from the product of arteriovenous. O2 content difference (CO2, a-v) and cardiac output (Qc), the latter being continuously measured with a transit-time ultrasonic flow probe placed around the main pulmonary artery. The VO2 (y) was linearly related to QO2 (x), y = 0.034 (SD 0.024) x + 29.3 (SD 3.9). The relationship between Qc (y) and CO2, a-v (x) was y = 4.6x(-1.12) (n = 69; r2 = 0.75; P = NS compared to the expected relationship for isoconsumption conditions, i.e. where Qc = VO2.(CO2, a v)(-1). Our data suggested that under stable conditions, an infusion of phentolamine did not sufficiently alter the relationship between Qc and CO2, a-v to invalidate its use for OFT in normal sheep. PMID- 1761013 TI - Monitoring exercise stress by changes in metabolic and hormonal responses over a 24-h period. AB - Metabolic and endocrine responses of 14 subjects of varying levels of fitness to an intensive anaerobic interval training session were assessed before exercise and at 2 h, 4 h, 8 h and 24 h postexercise. The endocrine response of the same subjects to a control day, where they were required not to exercise, was also assessed and compared with the values obtained on the interval training day. Uric acid, urea, and creatine phosphokinase concentrations still remained elevated above pre-exercise values 24 h postexercise. Lactate, creatinine, testosterone and cortisol concentrations were significantly elevated above pre-exercise values immediately postexercise but these had reversed by 2 h postexercise. Over the remainder of the recovery period testosterone concentrations remained significantly lower than values measured at similar times on the control day. This was shown to be due directly to a change in testosterone as sex hormone binding globulin concentration remained constant throughout the recovery period. The data indicate that when comparisons of data were made to control (rest) days, imbalances in homeostasis, due to intensive training, are not totally reversed within the next 24-h. The data also demonstrate that the parameters measured undergo the same variations in subjects with a wide range of physical fitness, indicating that these parameters could be used to monitor exercise stress and recovery in athletes of a wide range of abilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761014 TI - Influence of anthropometric characteristics on changes in maximal exercise ventilation and breathing pattern during growth in boys. AB - The aim of this study was to investigate the effect of growth on ventilation and breathing pattern during maximal exercise oxygen consumption (VO2max) and their relationships with anthropometric characteristics. Seventy six untrained schoolboys, aged 10.5-15.5 years, participated in this study. Anthropometric measurements made included body mass, height, armspan, lean body mass, and body surface area. During an incremental exercise test, maximal ventilation (VEmax), tidal volume (VTmax), breathing frequency (fmax), inspiratory and expiratory times (tImax and tEmax), total duration of respiratory cycle (tTOTmax), mean inspiratory flow (VT/tImax), and inspiration fraction (tI/tTOTmax) were measured at VO2max. A power function was calculated between anthropometric characteristics and ventilatory variables to determine the allometric constants. The results showed firstly, that VEmax, VTmax, tImax, tEmax, tTOTmax, and VT/tImax increased with age and anthropometric characteristics (P less than 0.001), fmax decreased (P less than 0.001), and tI/tTOTmax remained constant during growth; secondly that lean body mass explained the greatest percentage of variance of VEmax (62.1%), VTmax (76.8%), and VT/tImax (70.6%), while anthropometric characteristics explained a slight percentage of variance of fmax and timing; and thirdly that VEmax, VTmax, and VT/tImax normalized by lean body mass did not change significantly with age. We concluded that at VO2max there were marked changes in ventilation and breathing pattern with growth. The changes in VEmax, VTmax, and VT/tImax were strongly related to the changes in lean body mass. PMID- 1761015 TI - Effects of muscarinic blockade on the thermic effect of oral or intravenous carbohydrate. AB - Muscarinic blockade by atropine has been shown to decrease the thermic effect of a mixed meal, but not of intravenous glucose. To further delineate the mechanisms involved in the atropine-induced inhibition of thermogenesis after a meal, plasma substrate and hormone concentrations, energy expenditure (EE) and substrate oxidation rates were measured before and during a continuous glucose infusion (44.4 mumol.kg-1.min-1) with or without atropine. After 2 h of glucose infusion, a 20-g oral fructose load was administered while the glucose infusion was continued. Plasma insulin concentrations attained a plateau at 596 (SEM 100) pmol.l-1 after 120 min of glucose infusion and were not affected by muscarinic blockade; plasma glucose concentrations peaked at 13.3 (SEM 0.5) mmol.l-1 at 90 min and decreased progressively thereafter; no difference was observed with or without atropine. Plasma free fatty acid and glucagon concentrations, with or without atropine, were both decreased to 201 (SEM 18) mumol.l-1 and 74 (SEM 4) ng.l-1, respectively, after 2 h of glucose infusion, and were not further suppressed after oral fructose. Carbohydrate oxidation rates (CHO(ox)) increased to 20.8 (SEM 1.4) mumol.kg-1.min-1 and lipid oxidation rates (Lox) decreased to 1.5 (SEM 0.3) mumol.kg-1.min-1 between 90 and 120 min after the beginning of glucose infusion and were not affected by atropine. Glucose-induced thermogenesis was similar with [6.5% (SEM 1.4%) of basal EE] or without [6.0% (SEM 1.0%), NS) muscarinic blockade during the 30 min preceding fructose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761016 TI - Measurement of anterior tibial muscle size using real-time ultrasound imaging. AB - Cross-sectional images of the anterior tibial muscle group were obtained using real-time ultrasound scanning in 17 normal women. From photographs taken of the images, the cross-sectional area (CSA) and two linear measurements of muscle cross-section were determined. A measurement of the shortest distance of the muscle depth was termed DS, and a measurement of the longest distance through the muscle group was termed DL. Both linear dimensions showed a positive correlation with CSA and the best correlations were obtained when the dimensions were squared or combined (DS x DL). The correlation values were: CSA vs DS2, r = 0.9; CSA vs DL2, r = 0.75 and CSA vs DS x DL, r = 0.88. An approximate value for CSA could be calculated from DS2 by the equation 2 x DS2 + 1. A shape ratio, obtained by dividing DL by DS, was consistent within the group [mean 2.1 (SD 0.2)] and characterised the muscle geometrically. The CSA of repeated scans was assessed for repeatability between-days and between-scans by analysis of variance and the coefficient of variation (CV) calculated. Areas were repeatable between-days (CV 6.5%) and between-scans (CV 3.6%). Linear dimensions of the anterior tibial muscle group reflected CSA and their potential for assessing changes in muscle size with atrophy and hypertrophy have yet to be established. PMID- 1761017 TI - Can cycle power predict sprint running performance? AB - A major criticism of present models of the energetics and mechanics of sprint running concerns the application of estimates of parameters which seem to be adapted from measurements of running during actual competitions. This study presents a model which does not perpetuate this solecism. Using data obtained during supra-maximal cycle ergometer tests of highly trained athletes, the kinetics of the anaerobic and aerobic pathways were modelled. Internal power wasted in the acceleration and deceleration of body limbs and the power necessary to overcome air friction was calculated from data in the literature. Assuming a mechanical efficiency as found during submaximal cycling, a power equation was constructed which also included the power necessary to accelerate the body at the start of movement. The differential equation thus obtained was solved through simulation. The model appeared to predict realistic times at 100 m (10.47 s), 200 m (19.63 s) and 400 m (42.99 s) distances. By comparison with other methods it is argued that power equations of locomotion should include the concept of mechanical efficiency. PMID- 1761018 TI - Step ergometry: is it task-specific training? AB - Maximal exercise responses were measured before and after 10 weeks of training in two groups of men, one trained on a treadmill (n = 12) and the other on a step ergometer (n = 9); the groups were pre- and post-tested on both machines to examine the specificity of the training modes. Training for both groups consisted of 3 days week-1, 30 min day-1, progressing to 50 min day-1, at an intensity of 75%-80% heart rate maximum reserve. Pre-training maximal oxygen uptake (VO2max) was significantly higher on the treadmill for both groups (X = 8.5%). VO2max increased 6.9% on the treadmill (P less than 0.05) and 6.9% (P greater than 0.05) on the step ergometer after treadmill training. The small increases may be attributed to the specificity of the testing protocols used to elicit VO2max. Significant (P less than 0.01) increases in VO2max were found for both modalities after step-ergometry training (treadmill = 11.8%; step ergometer = 23.2%). These increases resulted in equal post-test VO2max values (4.05 l min-1; 51 ml kg-1 min 1) on the step ergometer and treadmill. The significant increases in VO2max found for both modalities after step-ergometry training shows that (1) step ergometry is an effective training modality, and (2) its effects can be measured on the treadmill and therefore it is not task-specific training. PMID- 1761019 TI - A simple and disposable sweat collector. AB - Apart from in cystic fibrosis, where sweat analysis provides valuable diagnostic information, sweat yields remain an overlooked biological fluid. Technical problems (dilution, condensation, contamination, evaporation, etc.) linked to currently available collection procedures are of concern and thwart their use. To overcome some of these technical difficulties, an original sweat-collection technique is described. A collection capsule is created inside a flexible, adhesive and disposable anchoring membrane pasted onto the skin. A fluid-tight window is positioned in the upper part of the pocket and gives access to its content. Through the collection window, complete emptying of the sweat collector can be achieved repeatedly by suction using a vacutainer tube inserted in a tube holder equipped with a long dull needle. With prior addition of a suitable marker, fractional samplings can also be performed using a precision micropipette. This collecting method allows for kinetic studies on sweat rate and sweat content. The limited bias-inducing manipulations linked to the described technique, coupled with the ease of performing kinetic studies on sweat volume and content, make this original tool a reliable and accurate sweat-collection technique. PMID- 1761020 TI - Blood lactate concentration following intermittent and continuous cycling tests of anaerobic capacity. AB - The purpose of this study was to compare the time and the magnitude of peak blood lactate concentration [La] following three 90-s cycle-ergometer tests. Intermittent all-out, continuous all-out, and continuous constant cycling tests were performed by 19 hockey players and 19 physical education students. Eight fingertip blood samples were drawn 1-11 min into recovery. [La] was similar between 3 min and 8 min of recovery for the three 90-s tests. [La] at the individual peak time was similar to that in samples taken at 1-4 min for the intermittent all-out test, 2-6 min for the continuous all-out test, and 2-4 min for the continuous constant cycling test. The intermittent and continuous all-out tests produced higher [La] at the individual peak time than did the continuous constant test. The intermittent all-out test produced an earlier peak [La] than the continuous tests. Both time and magnitude of peak [La] are dependent on the mode of testing. PMID- 1761021 TI - Twitch potentiation during fatiguing exercise in the elderly: the effects of training. AB - Twitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly. Following 12 weeks of resistance training in the elderly, there was no significant change in the twitch contractile properties at rest, but there was a significant main effect of training on the degree of twitch potentiation during the same fatigue protocol (peak potentiation 192% post-training vs 165% pretraining). These data suggest that the mechanism(s) responsible for twitch potentiation following MVCs may be influenced by both aging and training. PMID- 1761022 TI - Predicted sweat rate in fluctuating thermal conditions. AB - The ISO 7933 Required Sweat Rate Index is inappropriate under conditions of fluctuating exposure. Time weighted average values can introduce large underestimations as, for hot conditions, the relationship between physical stress and physiological strain is not linear. Mean skin temperature and sweat rate vary as a first order system, that is, according to an exponential averaging system, in response to a step function of the primary parameters. A very simple algorithm has been derived to take into account this exponential averaging and to predict the sweat rate at any time, taking into account the past exposure of the subject. It is based on time constants of 3 min for the mean skin temperature and of 25 min (up to a sweat rate of 50 W.m-2) and 10 min for the sweat rate. The correlation coefficient is 0.780 between observed and predicted sweat rates in independent experiments used for the validation of the model. This emphasises the necessity for exponential averaging as differences between individuals are very important and the precision of the observed data in these experiments was lower than for laboratory experimental data. PMID- 1761023 TI - Structural and metabolic properties of rat muscle exposed to weightlessness aboard Cosmos 1887. AB - Male Wistar rats were subjected to 12.5 days of weightlessness aboard Cosmos 1887. Histomorphometric and biochemical analyses were investigated in soleus (SOL), plantaris (PL) and extensor digitorum longus (EDL) muscles of flight rats (group F) and compared with data from two groups of terrestrial controls: one group living free in a vivarium (group V) and another subjected to a flight simulation except for the state of weightlessness (group S). Relative to groups V and S, no alteration in the percentage distribution of fibres had occurred in SOL, PL or EDL, after the flight. In SOL muscles from group F animals, cross sectional areas of all fibre types were reduced to a greater extent (-40%) than capillary to fibre ratio (-24%) leading to a higher capillary density (+33%) than in V and S groups. In PL, type I, IIA and IIB fibre cross-sectional areas were less decreased (-25%). In EDL, only fast-twitch fibre cross-sectional areas showed an average decrease of 30%. Capillary per fibre ratio was reduced by 15% and 28% respectively in PT and EDL muscles from group F rats compared to control groups V and S. Citrate synthase and 3-hydroxyacyl-coenzyme A dehydrogenase activities remained unchanged in SOL, PL and EDL following spaceflight. These findings indicate greater atrophy and functional alterations (capillarity) compared to those observed after 7 days of microgravity on Cosmos 1667. PMID- 1761024 TI - Development of muscle fatigue during intermittent submaximal static contraction in an agonist heterogeneous muscle group. AB - A comparison of the mean power frequency (MPF) and the root mean square amplitude (rms) of the myo-electric signal of two agonist muscles [triceps brachii (fast; TB) and anconeus (slow; ANC)] has been made during repeated intermittent static contractions. Subjects were asked to maintain different extension torques at 50% of maximal voluntary contraction until this could no longer be maintained (endurance time). The interval between successive contractions was kept constant at 3 min. During the first six successive contractions, a decrease in MPF and an increase in rms were most pronounced, ANC and TB MPF recovered with subsequent overshoot. A marked decline in endurance time was also seen. The increase in rms was greater for TB than for ANC when the decrease in MPF was greater for ANC than for TB. The differences in power spectrum density function upper frequencies of the two muscles could explain the greater decrease of MPF in ANC. Our data would suggest a greater fatigability in TB relative to ANC. On and after the seventh contraction, a steady-state in duration, muscle temperature, MPF and rms was reached. These results suggested that a slow (ANC) and a fast (TB) muscle acted in a similar way during intermittent static contractions, when the intervening rest was not long enough to allow full recovery of the muscles. PMID- 1761025 TI - Kinetics of ventilation and gas exchange during supine and upright cycle exercise. AB - The dynamics of ventilation (VE), oxygen uptake (VO2), carbon dioxide output (VCO2), and heart rate (fc) were studied in 12 healthy young men during upright and supine exercise. Responses to maximal and to two different types of submaximal exercise tests were contrasted. During incremental exercise to exhaustion, the maximal work rate, VO2max, VEmax, fc,max, and ventilatory threshold were all significantly reduced in supine compared to upright exercise (P less than 0.01-0.001). Following step increases or decreases in work rate between 25 W and 105 W, both VO2 and VCO2 responded more slowly in supine than upright exercise. Dynamics were also studied in two different pseudorandom binary sequence (PRBS) exercise tests, with the work rate varying between 25 W and 105 W with either 5-s or 30-s durations of each PRBS unit. In both of these tests, there were no differences caused by body position in the amplitude or phase shifts obtained from Fourier analysis for any observed variable. These data show that the body position alters the dynamic response to the more traditional step increase in work rate, but not during PRBS exercise. It is speculated that the elevation of cardiac output observed with supine exercise in combination with the continuously varying work-rate pattern of the PRBS exercise allowed adequate, perhaps near steady-state, perfusion of the working muscles in these tests, whereas at the onset of a step increase in work rate, greater demands were placed on the mechanisms of blood flow redistribution. PMID- 1761026 TI - Basketball exercise and secretory immunoglobulin A. AB - This study examined saliva levels of immunoglobulin A (IgA) before and after three games and three practice sessions during the basketball season. Saliva was collected from 27 prepubescent boys (10-12 years) in a small Fry league and 23 postpubescent boys (16-18 years) on a high school varsity team. Saliva samples were frozen for later assay using a standard enzyme-linked immunosorbent assay technique. IgA levels were significantly increased after games 1 and 3 in both age groups and after practice 3 in the high school athletes. Over the 2 months of saliva collections the pre-exercise IgA increased significantly with games 2 and 3 higher than game 1, and practice 3 higher than practices 1 and 2, in both age groups. These results indicate that basketball exercise can increase saliva IgA levels and that chronic exercise over the basketball season may increase the resting levels of IgA. These changes may give athletes more protection against respiratory infections both after exercise and in the resting state later in the season. PMID- 1761027 TI - Sulfur-containing cyclic ketimines and imino acids. A novel family of endogenous products in the search for a role. AB - Aminoethylcysteine, lanthionine, cystathionine and cystine are mono-deaminated either by L-amino-acid oxidase or by a transaminase exhibiting the properties described for glutamine transaminase. The deaminated products cyclize producing the respective ketimines. Authentic samples of each ketimine were prepared by reacting the appropriate aminothiol compound with bromopyruvate, except cystine ketimine which required the interaction of thiopyruvate with cystine sulfoxide. Reduction of the first three mentioned ketimines with NaBH4 yields the respective derivatives with the saturated rings of thiomorpholine and hexahydrothiazepine. The same reduction is carried out enzymically by a reductase extracted from mammalian tissues. Properties of the members of this family of compounds are described. Gas chromatography followed by mass spectrometry permits the identification of most of these products. HPLC is very useful for the determination of the ketimines by taking advantage of specific absorbance at 380 nm obtained by prior derivatization with phenylisothiocyanate. Adaptation of these and other analytical procedures to biological samples disclosed the presence of most of these compounds in bovine brain and in human urine. By using [35S]lanthionine ketimine as a representative member of the ketimine group, the specific, high-affinity, saturable and reversible binding to bovine brain membranes has been demonstrated. The binding is removed by aminoethylcysteine ketimine and by cystathionine ketimine indicating the occurrence in bovine brain of a common binding site for ketimines. The reduced ketimines are totally ineffective in competing with [35S]lanthionine ketimine. Alltogether these findings are highly indicative for the existence in mammals of a novel class of endogenous sulfur-containing cyclic products provided with a possible neurochemical function to be investigated further. PMID- 1761028 TI - Structural role of amino acids 99-110 in recombinant human erythropoietin. AB - Erythropoietin is the prime regulator of red blood cell production. Previous studies demonstrated that antipeptide antibodies to amino acids 99-119 and 111 129 bind to two non-overlapping domains and inhibit the hormone's action (Sytkowski, A.J. & Donahue, K. A. (1987) J. Biol. Chem. 262, 1161-1165). Oligonucleotide-directed mutagenesis now shows that amino acids 99-110 (domain 1) but not 119-129 (domain 2) are important to erythropoietin's structure and function. Mutagenesis of wild-type human erythropoietin cDNA was used to produce a series of mutant proteins with sequential deletion of three adjacent amino acids and insertion of the sequence Glu-Phe across the two domains. Transient expression in COS-7 cells revealed 2.0-kb transcripts encoded by all of the cDNAs. Domain 2 mutants exhibited specific biological activities similar to that of the wild type. In contrast, domain 1 mutants were not secreted. In vitro transcription and translation of the domain 1, domain 2 and wild-type cDNAs resulted in the isolation of 23.5-kDa and 32-kDa proteins in the absence or presence of pancreatic microsomes, respectively, consistent with efficient translation of all of the mutants and equivalent post-translational processing of each protein. The data suggest that mutation within domain 1 results in the intracellular biosynthesis of erythropoietins with altered structure, rendering them subject to rapid degradation. The bioassay of erythropoietins synthesized entirely in vitro demonstrated that domain 1 mutants were inactive, whereas both wild type and domain 2 mutant hormones exhibited biologic activity. The results are consistent with a critical role for amino acids 99-110 in the structure of human erythropoietin. PMID- 1761029 TI - Self-catalysed affinity labeling of Q beta replicase. AB - The spatial neighbourhood of the active center of Q beta replicase can be selectively modified by the method of self-catalysed affinity labeling. In the template-directed, mainly intramolecular enzymatic catalysis, the product [32P]GpG becomes specifically attached to the beta subunit. Using limited digestion of the radioactively labeled polypeptide by cyanogen bromide or N chlorosuccinimide, we have mapped the attachment site to the region of subunit beta between Trp93 and Met130. Under our reaction conditions, Lys95 is the amino acid most likely to be modified, suggesting that Lys95 lies near the nucleotide binding site in the active center. PMID- 1761030 TI - Patchwork-structure serpins from silkworm (Bombyx mori) larval hemolymph. AB - A new serpin (serine proteinase inhibitor), having antichymotryptic activity, was isolated from silkworm, Bombyx mori, larval hemolymph and was named silkworm antichymotrypsin II (sw-AchyII). Amino-acid-sequence analysis of sw-AchyII revealed that it consisted of 375 amino acids without cysteine or glycosylated residues. sw-AchyII formed an SDS-undissociable complex with alpha-chymotrypsin, but this complex was broken down at pH 12.5 into alpha-chymotrypsin and sw-AchyII in which the reactive site was cleaved. Amino-acid-sequence analysis after cleavage identified in P1-P1' residue at the reactive site of sw-AchyII as Phe340 Met341. The amino acid sequence from the amino terminus to residue 336 was completely identical to the corresponding region of sw-AT [Takagi, H., Narumi, H., Nakamura, K. & Sasaki, T. (1990) J. Biochem. (Tokyo) 108, 372-378]. The degree of similarity between sw-AchyII and silkworm antitrypsin (sw-AT) from residue 337 to the carboxy terminus was only 46%. Reactive sites of both serpins were in the variable regions. PMID- 1761031 TI - Role of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase. AB - Drosophila alcohol dehydrogenase (ADH), an NAD(+)-dependent dehydrogenase, shares little sequence similarity with horse liver ADH. However, these two enzymes do have substantial similarity in their secondary structure at the NAD(+)-binding domain [Benyajati, C., Place, A. P., Powers, D. A. & Sofer, W. (1981) Proc. Natl Acad. Sci. USA 78, 2717-2721]. Asp38, a conserved residue between Drosophila and horse liver ADH, appears to interact with the hydroxyl groups of the ribose moiety in the AMP portion of NAD+. A secondary-structure comparison between the nucleotide-binding domain of NAD(+)-dependent enzymes and that of NADP(+) dependent enzymes also suggests that Asp38 could play an important role in cofactor specificity. Mutating Asp38 of Drosophila ADH into Asn38 decreases Km(app)NADP 62-fold and increases kcat/Km(app)NADP 590-fold at pH 9.8, when compared with wild-type ADH. These results suggest that Asp38 is in the NAD(+) binding domain and its substituent, Asn38, allows Drosophila ADH to use both NAD+ and NADP+ as its cofactor. The observations from the experiments of thermal denaturation and kinetic measurement with pH also confirm that the repulsion between the negative charges of Asp38 and 2'-phosphate of NADP+ is the major energy barrier for NADP+ to serve as a cofactor for Drosophila ADH. PMID- 1761032 TI - Specific inhibition of endopeptidase 24.16 by dipeptides. AB - The inhibitory effect of various dipeptides on the neurotensin-degrading metallopeptidase, endopeptidase 24.16, was examined. These dipeptides mimick the Pro10-Tyr11 bond of neurotensin that is hydrolyzed by endopeptidase 24.16. Among a series of Pro-Xaa dipeptides, the most potent inhibitory effect was elicited by Pro-Ile (Ki approximately 90 microM) with Pro-Ile greater than Pro-Met greater than Pro-Phe. All the Xaa-Tyr dipeptides were unable to inhibit endopeptidase 24.16. The effect of Pro-Ile on several purified peptidases was assessed by means of fluorigenic assays and HPLC analysis. A 5 mM concentration of Pro-Ile does not inhibit endopeptidase 24.11, endopeptidase 24.15, angiotensin-converting enzyme, proline endopeptidase, trypsin, leucine aminopeptidase, pyroglutamyl aminopeptidase I and carboxypeptidase B. The only enzyme that was affected by Pro Ile was carboxypeptidase A, although it was with a 50-fold lower potency (Ki approximately 5 mM) than for endopeptidase 24.16. By means of fluorimetric substrates with a series of hydrolysing activities, we demonstrate that Pro-Ile can be used as a specific inhibitor of endopeptidase 24.16, even in a complex mixture of peptidase activities such as found in whole rat brain homogenate. PMID- 1761033 TI - Single amino acid substitutions in the B870 alpha and beta light-harvesting polypeptides of Rhodobacter capsulatus. Structural and spectral effects. AB - To obtain information on the structural and functional role of highly conserved amino acid residues in the B870 alpha and beta light-harvesting polypeptides of Rhodobacter capsulatus, site-directed mutagenesis was performed. 18 mutants with single amino acid substitutions at nine different positions in the B870 antenna polypeptides were prepared in a B800-850-lacking strain. The characterization of the resulting phenotypes was based on a quantification of the core-complex elements (reaction center, light-harvesting polypeptides, bacteriochlorophyll a and carotenoid) and the core-complex spectral characteristics (absorption maximum, absorption coefficient and fluorescence intensity). These data generally showed that strong structural effects were caused by the amino acid substitutions. Thus, the three tryptophan exchanges at the position alpha 8 resulted in either the absence of a core complex (alpha Trp8----Leu), the absence of the core antenna (alpha Trp8----Ala) or a reduction in the carotenoid content (alpha Trp8----Tyr). Likewise, the mutants alpha Pro13Gly (i.e. alpha Pro13--- Gly), beta Gly10Val and alpha Phe23Ala demonstrated an abnormal protein/pigment ratio in the core antenna, while a drastically reduced antenna size resulted from the amino acid exchange beta Arg45Asp. In contrast to the structural effects, the absorption maxima and the fluorescence intensities of the mutant antennae differed only slightly from the wild type. The strongest blue shift of the bacteriochlorophyll a (8-11 nm) was induced by substitutions of the Trp at position alpha 43 (alpha Trp43----Ala, Leu or Tyr). Contrary to the other spectral effects, the absorption coefficient of bacteriochlorophyll a was strongly influenced by the amino acid substitutions and varied by 1.6-times less (beta Arg45Asp) and 1.3-times greater (alpha Phe25Ala) than normal. The antenna free mutant, alpha Trp8Ala, yielded a high rate of B800-850 revertants during phototrophic growth, indicating a direct energy transfer from the B800-850 antenna to the reaction center in these strains. Although conditions for growth were generally observed to influence phenotypic expression, the structural as well as spectral effects were demonstrated to differ to the greatest extent between chemotrophically grown and phototrophically grown cells. PMID- 1761034 TI - Cloning and expression of the gene encoding the soluble cytochrome b562 of Escherichia coli. AB - The gene for the soluble cytochrome b562 from Escherichia coli B has been cloned on a SalI fragment. The analysis of the gene reveals the presence of a leader sequence in front of the sequence encoding the mature protein. Expression of cytochrome b562 using the lac-promoter produced the protein to a level of 3-5% of total protein. This over-production enables employment of a simple, high-yield purification protocol to obtain homogeneous cytochrome b562. Spectroscopic and N terminal sequence analyses of the purified protein demonstrate that it is identical to the chromosomally expressed cytochrome b562 purified and characterized from E. coli B [Itagaki, E. & Hager, L.P. (1966) J. Biol. Chem. 241, 3687-3695]. It is demonstrated that the genomic sequence codes for a classic N-terminal signal sequence and that mature cytochrome b562 is translocated to the periplasmic space. PMID- 1761035 TI - 1H NMR studies of echistatin in solution. Sequential resonance assignments and secondary structure. AB - Two-dimensional 1H-NMR methods have been used to obtain complete proton resonance assignments for the 49-residue protein echistatin from the viper Echis carinatus. The protein in solution contains only a small amount of regular secondary structure with four very short beta-strands. These beta-strands form two short segments of antiparallel beta-sheet, as evidenced by the observed cross-strand NOE. The first two strands are connected with a tight reverse turn, whereas the remaining two strands are linked together by an 11-residue loop forming a so called hairpin. The tripeptide unit Arg-Gly-Asp, responsible for the binding of echistatin to the fibrinogen receptor glycoprotein GPIIb/IIIa, is located at the tip of this very hydrophilic loop. PMID- 1761036 TI - Nuclear magnetic resonance studies of the snake toxin echistatin. 1H resonance assignments and secondary structure. AB - The 1H-NMR spectrum of the snake toxin echistatin has been assigned using homonuclear two-dimensional methods. Consideration of the NOE patterns, coupling constants and putative hydrogen bonds enabled two regular features of secondary structure to be deduced: a beta-sheet/turn between residues 8 and 13 and a small anti-parallel beta-sheet and bulge linking residues 16-20 with residues 30-33. The recognition region of the protein containing the residues RGD lies in a loop joining the two strands of the beta-sheet. The beta-bulge and the loop containing the RGD sequence undergo pH-dependent conformational interconversion, modulated by the side chain of Asp29. PMID- 1761037 TI - The secondary structure of echistatin from 1H-NMR, circular-dichroism and Raman spectroscopy. AB - Detailed biophysical studies have been carried out on echistatin, a member of the disintegrin family of small, cysteine-rich, RGD-containing proteins, isolated from the venom of the saw-scaled viper Echis carinatus. Analysis of circular dichroism spectra indicates that, at 20 degrees C, echistatin contains no alpha helix but contains mostly beta-turns and beta-sheet. Two isobestic points are observed as the temperature is raised, the conformational changes associated with that observed between 40 degrees C and 72 degrees C being irreversible. Raman spectra also indicate considerable beta-turn and beta-sheet (20%) structure and an absence of alpha-helical structure. Three of the four disulphide bridges are shown to be in an all-gauche conformation, while the fourth adopts a trans-gauche gauche conformation. The 1H-NMR spectrum of echistatin has been almost fully assigned. A single conformation was observed at 27 degrees C with the four proline residues adopting only the trans conformation. A large number of backbone amide protons were found to exchange slowly, but no segments of the backbone were found to be in either alpha-helical or beta-sheet conformation. A number of turns could be characterised. An irregular beta-hairpin contains the RGD sequence in a mobile loop at its tip. Two of the four disulphide cross-links have been identified from the NMR spectra. The data presented in this paper will serve to define the structure of echistatin more closely in subsequent studies. PMID- 1761038 TI - Sequence-specific 1H-NMR assignment and secondary structure of the Tyr41----His mutant of the single-stranded DNA binding protein, gene V protein, encoded by the filamentous bacteriophage M13. AB - Sequence-specific 1H-NMR assignments are reported for the Tyr41----His (Y41H) mutant of the single-stranded DNA binding protein, encoded by gene V of the filamentous bacteriophage M13 (GVP). The mutant protein was chosen for this purpose because it exhibits significantly improved solubility characteristics over wild-type GVP [Folkers et al. (1991) Eur. J. Biochem. 200, 139-148]. The secondary structure elements present in the protein are deduced from a qualitative interpretation of the nuclear Overhauser enhancement spectra and amide exchange data. The protein is entirely composed of antiparallel beta structure. It is shown that identical structural elements are present in wild type GVP. Previously, we have demonstrated that the secondary structure of the beta-loop, encompassing residues 13-31 which is present in GVP in solution, deviates from that proposed for the same amino acid sequence on the basis of X ray diffraction data [van Duynhoven et al. (1990) FEBS Lett. 261, 1-4]. Now that we have arrived at a complete description of the secondary structure of the protein in solution, other deviations with respect to the crystallographically determined structure became apparent as well. The N-terminal part of the protein is, in solution, part of a triple-stranded beta-sheet while, in the crystal, it is an extended strand pointing away from the bulk of the protein dimer. One of the antiparallel beta-sheets in the protein which had been designated earlier as the complex loop has, in the solution structure, a different pairwise arrangement of the residues in its respective beta-ladders. Residues 30 and 48 are opposite to one another in the solution structure while in the crystal structure residues 32 and 48 are paired. A similar observation is made for the so-called dyad domain of the protein of which the beta-sheet in the solution structure is shifted by one residue with respect to that of the crystal structure. PMID- 1761039 TI - Structural and functional relationships in two families of beta-1,4-glycanases. AB - CenA and Cex are beta-1,4-glycanases produced by the cellulolytic bacterium Cellulomonas fimi. Both enzymes are composed of two domains and contain six Cys residues. Two disulfide bonds were assigned in both enzymes by peptide analysis of the isolated catalytic domains. A further disulfide bond was deduced in both cellulose-binding domains from the absence of free thiols under denaturing conditions. Corresponding Cys residues are conserved in eight of nine other known C. fimi-type cellulose-binding domains. CenA and Cex belong to families B and F, respectively, in the classification of beta-1,4-glucanases and beta-1,4-xylanases based on similarities in catalytic domain primary structure. Disulfide bonds in the CenA catalytic domain correspond to the two disulfide bonds in the catalytic domain of Trichoderma reesei cellobiohydrolase II (family B) which stabilize loops forming the active-site tunnel. Sequence alignment indicates the probable occurrence of disulfides at equivalent positions in the two other family B enzymes. Partial resequencing of the gene encoding Streptomyces KSM-9 beta-1,4 glucanase CasA (family B) revealed five errors in the original nucleotide sequence analysis. The corrected amino acid sequence contains an Asp residue corresponding to the proposed proton donor in hydrolysis catalysed by cellobiohydrolase II. Cys residues which form disulfide bonds in the Cex catalytic domain are conserved in XynZ of Clostridium thermocellum and Xyn of Cryptococcus albidus but not in the other eight known family F enzymes. Like other members of its family, Cex catalyses xylan hydrolysis. The catalytic efficiency (kcat/Km) for hydrolysis of the heterosidic bond of p-nitrophenyl-beta D-xylobioside is 14,385 min-1.mM-1 at 25 degrees C; the corresponding kcat/Km for p-nitrophenyl-beta-D-cellobioside hydrolysis is 296 min-1.mM-1. PMID- 1761040 TI - The effect of water content and nature of organic solvent on enzyme activity in low-water media. A quantitative description. AB - A simple theoretical model was suggested to describe quantitatively the effect of water content and nature of organic solvents on catalytic behavior of enzymes suspended in low-water media. The model was based on a generally accepted notion that the destruction of the protein hydration shell is one of the main reasons for protein denaturation by organic solvents. The validity of the model was confirmed by the example of catalytic behavior of immobilized laccase suspended in water/organic mixtures of different compositions. In addition, the results were used to demonstrate that the effect of organic solvents and/or water content on catalytic behavior of enzymes in low-water media can be adequately assessed only in terms of the full kinetic description based on properly determined Vm and Km values. PMID- 1761041 TI - Inactivation of pancreatic and gastric lipases by tetrahydrolipstatin and alkyl dithio-5-(2-nitrobenzoic acid). A kinetic study with 1,2-didecanoyl-sn-glycerol monolayers. AB - We studied the covalent inhibition of lipases by the monolayer technique. We report the inactivation of porcine pancreatic and human and rabbit gastric lipases, acting on mixed monomolecular films of dicaprin containing tetrahydrolipstatin or new hydrophobic disulfide compounds, which can be described as a 'poisoned-interface' system. A kinetic model is presented for depicting the covalent inactivation of lipolytic enzymes at a lipid/water interface. The stoichiometry of the interfacial situation can be described as follows: one lipase molecule embedded among 10(5) substrate molecules will be inactivated to half its initial velocity by the presence of 10 tetrahydrolipstatin molecules. This inactivation was independent of the surface pressure. When tested in the form of mixed films, all the disulfide compounds investigated specifically reduced the hydrolysis of 1,2-didecanoyl-sn-glycerol films by gastric lipases, but did not affect hydrolysis by pancreatic lipase. With this poisoned-interface system, tetrahydrolipstatin was found to be the most potent inactivator, whereas disulfide compounds showed a higher degree of selectivity than tetrahydrolipstatin. PMID- 1761042 TI - A calorimetric study of the Ni(II)-5' AMP system. A base-stacking stabilization. AB - The thermodynamic parameters of the interaction between Ni(II) (M) and 5'-AMP in aqueous solution were determined calorimetrically (I = 0.1 tetramethylammonium bromide, 25 degrees C) at physiological pH. The experimental conditions were carefully selected to avoid the polynuclear complex formation. From the Ni(5'AMP) complex-formation constant (logK1 = 2.55), the Ni(5'AMP)2(2-)-complex-formation constant and the Ni(5'AMP) (ML) and Ni(5'AMP)2(2-) (ML2) complex-formation enthalpies were determined (logK2 = 2.34, delta H1 = -10.0 kJ/mol and delta H2 = 21.6 kJ/mol). These results confirm the formation of the ML2 complex in solution and agree very well with the hypothesis of the 'stacking' between the purine rings, promoted for metal ions. PMID- 1761043 TI - Biochemical and biophysical investigations of the ferrocene-iron-loaded rat. An animal model of primary haemochromatosis. AB - Male Wistar rats fed with ferrocene had high hepatic iron loading (7.24 +/- 1.97 mg Fe/g tissue) after 6 weeks, principally located in lysosomes, which was comparable to the levels and distribution determined in human haemochromatosis. The two iron-storage proteins, ferritin and haemosiderin were isolated from the livers of the ferrocene-loaded rats and their iron cores were investigated by Mossbauer spectroscopy and inductively coupled plasma-emission spectrometry. Ferrihydrite was the predominant form of iron present in both ferritin and haemosiderin, while haemosiderin contained higher amounts of phosphorus, magnesium, calcium and barium, then either normal or ferrocene-loaded ferritin. Free-radical-mediated damage in the iron-loaded livers was inferred by the significant depletion of alpha-tocopherol in both the livers and subcellular hepatic lysosomal fraction, which inversely correlated with the increasing iron content (r = -0.61; P less than 0.05) and was associated with increased fragility of the lysosomal membranes. PMID- 1761044 TI - The distribution of permeant ions demonstrates the presence of at least two distinct electrical gradients in bloodstream forms of Trypanosoma brucei. AB - The distribution of 86Rb+ and the radiolabelled lipophilic cation [3H]methyltriphenylphosphonium (MePh3P+) was used to investigate the membrane potentials that exist in bloodstream forms of Trypanosoma brucei. Even after correction for binding to cellular constituents, the accumulation of MePh3P+ was approximately tenfold greater than the accumulation of Rb+ under resting conditions. The addition of low concentrations of carbonylcyanide p trifluoromethoxyphenylhydrazone or valinomycin reduced the accumulation of MePh3P+ tenfold without perturbing the accumulation of Rb+. Although selective permeabilization of the plasma membrane abolished the accumulation of Rb+ and caused a substantial decrease in the accumulation of MePh3P+, a significant carbonylcyanide-p-trifluoromethoxyphenylhydrazone-sensitive accumulation of MePh3P+ persisted under these conditions. These data were consistent with the presence of at least two distinct membrane potentials (delta psi) in bloodstream forms of T. brucei; a potential across the plasma membrane (delta psi p) and an additional delta psi, generated by the electrogenic movement of H+, across the membrane of an intracellular organelle that possesses no electrical permeability to Rb+ or K+. PMID- 1761045 TI - The solution structure of a monomeric insulin. A two-dimensional 1H-NMR study of des-(B26-B30)-insulin in combination with distance geometry and restrained molecular dynamics. AB - The solution conformation of des-(B26-B30)-insulin (DPI) has been investigated by 1H-NMR spectroscopy. A set of 250 approximate interproton distance restraints, derived from two-dimensional nuclear Overhauser enhancement spectra, were used as the basis of a structure determination using distance geometry (DG) and distance bound driven dynamics (DDD). Sixteen DG structures were optimized using energy minimization (EM) and submitted to short 5-ps restrained molecular dynamics (RMD) simulations. A further refinement of the DDD structure with the lowest distance errors was done by energy minimization, a prolonged RMD simulation in vacuo and a time-averaged RMD simulation. An average structure was obtained from a trajectory generated during 20-ps RMD. The final structure was compared with the des-(B26 B30)-insulin crystal structure refined by molecular dynamics and the 2-Zn crystal structure of porcine insulin. This comparison shows that the overall structure of des-(B26-B30)-insulin is retained in solution with respect to the crystal structures with a high flexibility at the N-terminal part of the A chain and at the N-terminal and C-terminal parts of the B chain. In the RMD run a high mobility of Gly A1, Asn A21 and of the side chain of Phe B25 is noticed. One of the conformations adopted by des-(B26-B30)-insulin in solution is similar to that of molecule 1 (Chinese nomenclature) in the crystal structure of porcine insulin. PMID- 1761046 TI - Determination of the orientations of tryptophan analogues bound to the trp repressor and the relationship to activation. AB - The antirepressor indole 3-propanoate has been shown by X-ray crystallography to bind in a different orientation compared with the natural corepressor for the tryp repressor, L-tryptophan (Lawson, C.L. & Sigler, P. B. (1988) Nature 333, 869 871). This suggests a simple difference between what constitutes a corepressor versus an antirepressor. We have used visible absorption and 1H-NMR spectroscopy to characterise the nature of several ligand-repressor complexes and DNA-binding assays to assess the relative operator binding affinities. 5-Fluorotryptophan binds with similar affinity and in the same orientation as L-tryptophan, and is an equally effective corepressor. In contrast, the tight-binding antirepressor indole 3-acrylate binds in the same orientation as indole 3-propanoate. Indole, also an antirepressor, also binds in the indole-3-propanoate orientation. 5 Methyltryptamine, a corepressor, shows spectroscopic characteristics of both tryptophan and indoleacrylate, though NOEs indicate that the tryptophan orientation is preferred. These results indicate that the ammonium group in the side chain is essential both for activation and binding in the L-tryptophan orientation. Antirepressors, lacking the ammonium group, bind in the more favourable indole-3-propanoate orientation. Differences in the NMR signatures of the different repressor-ligand complexes indicate that the details of the conformations depend on the nature of the ligands and their orientation within the binding site. Despite any conformational rearrangement of the protein on binding, dissociation of ligands is facile: 5-fluorotryptophan dissociates rapidly at 313 K. These findings complement and extend the X-ray and thermodynamic analyses of ligand binding. PMID- 1761047 TI - Mechanism of action of deoxyribonuclease II from human lymphoblasts. AB - Deoxyribonuclease II has been purified through five fractionation steps from the human lymphoblast cell line K562. Isolation included DEAE-cellulose and heparin agarose chromatography followed by fractionation on Mono-S, Mono-Q and Superose 12 FPLC columns. In an extension of previous studies, deoxyribonuclease II was found to introduce a much higher proportion of single-strand nicks relative to double-strand breaks into supercoiled DNA than has been reported for linear DNA. Application of DNA sequencing techniques has further revealed a unique resistance of 3' termini to hydrolysis by this enzyme. Deoxyribonuclease II cleaves at every available site along the duplexed portion of a paired oligonucleotide substrate with the exception of the last four nucleotides. Consistent with previous results, this deoxyribonuclease II is active at low pH in the absence of Mg2+ and is not inhibited by EDTA, but complete inhibition is observed with 100 microM Fe3+. Likewise we confirmed the presence of 3'-phosphoryl termini on the DNA cleavage products since they failed to function as primers for DNA synthesis catalyzed by Escherichia coli DNA polymerase I. PMID- 1761048 TI - Geotrichum candidum produces several lipases with markedly different substrate specificities. AB - We have purified and examined the substrate specificity of four lipases from two strains of the mould Geotrichum candidum, ATCC 34614 and CMICC 335426. We have designated the lipases I and II (ATCC 34614), and A and B (CMICC 335426). The enzymes are monomeric and have similar molecular masses and pI. Thus, lipases I and II have native molecular masses of 50.1 kDa and 55.5 kDa, and pI of 4.61 and 4.47, respectively. Lipases A and B are very similar to lipases I and II with native molecular masses of 53.7 kDa and 48.9 kDa, and pI of 4.71 and 4.50, respectively. Treatment with endo-beta-N-acetylglucosaminidase caused a reduction in molecular mass of approximately 4.5 kDa for all four lipases, indicating that these enzymes are glycosylated. Western blotting shows that the lipases are related. However, lipase B from CMICC 335426 shows a remarkable specificity for unsaturated substrates with a double bond at position 9 (cis configuration), and this specificity is not exhibited by the other three lipases. No lipase of this unique specificity has previously been purified to homogeneity. Structural studies using these four lipases should allow insight into the molecular basis of this remarkable specificity. PMID- 1761049 TI - Notechis 11'2, a non-toxic phospholipase A2 from the venom of Notechis scutatus scutatus. AB - Previously, we deduced the amino acid sequence of a novel phospholipase-A2-like protein (PLA2) from the nucleotide sequence of a cDNA isolated from a library prepared from the venom gland of the Australian elapid Notechis scutatus scutatus. The corresponding protein has now been identified, purified from the venom and named Notechis 11'2. Its complete amino acid sequence has been determined by automated Edman degradation of both the whole protein and peptides generated by Staphylococcus aureus protease digestion and chemical cleavage at a tryptophan residue. As predicted from its sequence which contains all the residues putatively required for PLA2 activity, Notechis 11'2 exhibits an esterase activity, preferentially against neutral phospholipids. However, despite its sequence homology with other highly toxic PLA2 present in the venom of Notechis scutatus scutatus, notechis 11'2 has no lethal activity. This observation further supports the view that the lethal activity of PLA2 from Notechis scutatus scutatus is not due to the esterasic activity only. PMID- 1761050 TI - Effect of N-glycan removal on the enzymatic activity of porcine thyroid peroxidase. AB - Active porcine thyroid peroxidase (pTPO) has been purified either by deoxycholate extraction followed by immunoaffinity purification (pTPO A) or by trypsin/digitonin extraction followed by ion-exchange and gelfiltration chromatography (pTPO B); pTPO A appeared as a full-length molecule, while pTPO B appeared as peptide fragments. Purified pTPO were deglycosylated either by peptide N-glycosidase F (PNGase F) or by endo-beta-N-acetylglucosaminidase H (endo H) treatment. Electrophoretic controls and affinity blotting with concanavalin A indicated that deglycosylation was not total and that pTPO was more efficiently deglycosylated by endo H than by PNGase F. The enzymatic activity of pTPO A, checked by guaiacol and iodide oxidation, was inhibited by PNGase F and endo H deglycosylation, while that of pTPO B was not. After deglycosylation, the apparent Km of pTPO A for guaiacol and iodide increased, while the Vmax for both substrates decreased. The state of aggregation of pTPO A before and after deglycosylation was checked by sucrose density-gradient centrifugation. Results indicated that this inhibition was not due to a loss of pTPO A solubility. These observations suggest that deglycosylation induced a modification of the tertiary structure of pTPO A which affected the active-site domain of the enzyme. PMID- 1761051 TI - Synthesis of dinucleoside polyphosphates catalyzed by firefly luciferase. AB - In the presence of ATP, luciferin (LH2), Mg2+ and pyrophosphatase, the firefly (Photinus pyralis) luciferase synthesizes diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) through formation of the E-LH2-AMP complex and transfer of AMP to ATP. The maximum rate of the synthesis is observed at pH 5.7. The Km values for luciferin and ATP are 2-3 microM and 4 mM, respectively. The synthesis is strictly dependent upon luciferin and a divalent metal cation. Mg2+ can be substituted with Zn2+, Co2+ or Mn2+, which are about half as active as Mg2+, as well as with Ni2+, Cd2+ or Ca2+, which, at 5 mM concentration, are 12-20-fold less effective than Mg2+. ATP is the best substrate of the above reaction, but it can be substituted with adenosine 5'-tetraphosphate (p4A), dATP, and GTP, and thus the luciferase synthesizes the corresponding homo-dinucleoside polyphosphates:diadenosine 5',5"'-P1,P5-pentaphosphate (Ap5A), dideoxyadenosine 5',5"'-P1,P4-tetraphosphate (dAp4dA) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G). In standard reaction mixtures containing ATP and a different nucleotide (p4A, dATP, adenosine 5'-[alpha,beta-methylene]-triphosphate, (Ap[CH2]pp), (S') adenosine-5'-[alpha-thio]triphosphate [Sp)ATP[alpha S]) and GTP], luciferase synthesizes, in addition to Ap4A, the corresponding hetero-dinucleoside polyphosphates, Ap5A, adenosine 5',5"'-P1,P4-tetraphosphodeoxyadenosine (Ap4dA), diadenosine 5',5"'-P1,P4-[alpha,beta-methylene] tetraphosphate (Ap[CH2]pppA), (Sp diadenosine 5',5"'-P1,P4-[alpha-thio]tetraphosphate [Sp)Ap4A[alpha S]) and adenosine-5',5"'-P1,P4-tetraphosphoguanosine (Ap4G), respectively. Adenine nucleotides, with at least a 3-phosphate chain and with an intact alpha phosphate, are the preferred substrates for the formation of the enzyme nucleotidyl complex. Nucleotides best accepting AMP from the E-LH2-AMP complex are those which contain at least a 3-phosphate chain and an intact terminal pyrophosphate moiety. ADP or other NDP are poor adenylate acceptors as very little diadenosine 5',5"'-P1,P3-triphosphate (Ap3A) or adenosine-5',5"'-P1,P3 triphosphonucleosides (Ap3N) are formed. In the presence of NTP (excepting ATP), luciferase is able to split Ap4A, transferring the resulting adenylate to NTP, to form hetero-dinucleoside polyphosphates. In the presence of PPi, luciferase is also able to split Ap4A, yielding ATP. The cleavage of Ap4A in the presence of Pi or ADP takes place at a very low rate. The synthesis of dinucleoside polyphosphates, catalyzed by firefly luciferase, is compared with that catalyzed by aminoacyl-tRNA synthetases and Ap4A phosphorylase. PMID- 1761052 TI - Isolation of a novel type-I fatty-acid synthetase from Euglena gracilis. Specific derepression in streptomycin-bleached cells. AB - A novel, high-molecular-mass fatty-acid synthetase (FAS) complex has been isolated from streptomycin-bleached Euglena gracilis cells. The enzyme was purified 250-fold from the crude cell homogenate and subsequently migrated upon SDS/PAGE as a single band of molecular mass 270 kDa. This apparent subunit size of the purified protein contrasted with a smaller size of only 200 kDa which was exhibited by the same protein upon immunoblotting of the crude cell extract. The purified Euglena FAS complex cosediments in a sucrose density gradient with yeast FAS and, from this, both enzymes were concluded to have the same overall molecular mass of 2.3 MDa. The enzyme described in this paper appears to be a typical type-I FAS multienzyme which clearly differs from the E. gracilis FAS so far described. Instead, it appears to be organized structurally similar to the type-I FAS multienzymes of lower fungi. In vitro, the purified Euglena FAS complex synthesizes mainly palmitic acid, or its CoA ester, from acetyl CoA and malonyl CoA as substrates. The Km values for acetyl CoA and malonyl CoA are 20 microM and 31 microM, respectively. Similar to the FAS enzymes of other lower eucaryotes, the Euglena type-I FAS is a flavoprotein. In contrast to yeast FAS, however, the flavin cofactor appears to be covalently attached to the enzyme protein. By immunological techniques, the enzyme was shown to be absent in green as well as in etiolated E. gracilis cells, while being rapidly induced upon streptomycin bleaching of heterotrophically growing green cells. The data suggest an inverse correlation between organellar development and derepression of this FAS complex. PMID- 1761053 TI - Purification and characterization of two xylanases from Trichoderma longibrachiatum. AB - Two endoxylanases were purified from the culture medium of Trichoderma longibrachiatum. Both enzymes were highly basic, and lacked activity on carboxymethyl-cellulose. An enzyme of 21.5 kDa (xylanase A) had a specific activity of 510 U/mg protein, a Km of 0.15 mg soluble xylan/ml, possessed transglycosidase activity and generated xylobiose and xylotriose as the major endproducts from xylan or xylose oligomers. A larger enzyme of 33 kDa (xylanase B) had a specific activity of 131 U/mg protein, a Km of 0.19 mg soluble xylan/ml, lacked detectable transglycosidase activity and generated xylobiose and xylose as major endproducts from xylan and xylose oligomers. Xylotriose was the smallest oligomer attacked by both enzymes. In addition, xylotriose inhibited hydrolysis of xylopentanose by both enzymes, while xylobiose appeared to inhibit xylanase B, but not xylanase A. PMID- 1761054 TI - Heparinase II from Flavobacterium heparinum. HPLC analysis of the saccharides generated from chemically modified heparins. AB - Saccharides produced by the action of heparinase II on native pig mucosal heparin (heparin IS), de-N-sulphated heparin (heparin IH), N-acetylheparin (heparin IA), de-N/O-sulphated heparin (heparin IVH), de-O-sulphated heparin (heparin IVS) and de-O-sulphated N-acetylheparin (heparin IVA) were analysed by reversed-phase HPLC using Spherisorb ODS2. Fractions obtained by gel filtration with Bio-Gel P-4 were similarly examined. Heparin IS gave delta UA-2S----GlcNS-6S (IS) as the major unsaturated disaccharide and lesser amounts of delta UA----GlcNS-6S (IIS), delta UA-2S----GlcNS (IIIS), delta UA----GlcNS (IVS), delta UA-2S----GlcNAc-6S (IA), delta UA----GlcNAc-6S (IIA), delta UA-2S----GlcNAc (IIIA) and delta UA----GlcNAc (IVA). Heparins IA, IVA and IVS gave as the predominant unsaturated disaccharide that corresponding to the major repeat structure of the polymer. These were respectively delta UA-2S----GlcNAc-6S (IA), delta UA-GlcNAc (IVA) and delta UA--- GlcNS (IVS). Minor disaccharides from the heterogeneous structure in native pig heparin and from residual O-sulphates after the de-O-sulphating process were detected. Heparin IH was degraded more slowly than any of the N-substituted heparins. The predominant unsaturated disaccharide was IH, which was derived from the major repeating unit. In addition, disaccharides IIH, IIIH, IA, IIA and IVA were detected. Heparin IVH showed little degradation, the unsaturated disaccharide IVH not being detected after 24 h. Disaccharide IVA was obtained from the heterogeneous sequence in heparin IVH. Several higher oligosaccharides were identified in the gel-filtration fractions including saccharides from the linkage region (for heparin IS and IVA) and the anti-thrombin binding site (for heparin IS only). A tetrasaccharide and hexasaccharide, with the structures delta UA----GlcNAc----UA----GlcNAc and delta UA----GlcNAc----UA----GlcNAc----UA--- GlcNAc, were present in the HPLC profiles of heparins IA and IVA. PMID- 1761055 TI - Volume changes in high-affinity calcium binding of the sarcoplasmic reticulum calcium-transport enzyme. AB - The effect which hydrostatic pressure exerts on the hydrolysis of dinitrophenyl phosphate and nitrophenyl phosphate by the sarcoplasmic reticulum calcium transport enzyme was determined. Activation volumes for substrate hydrolysis at saturating and non-saturating concentrations of calcium were determined and used to evaluate volume increments for initial calcium binding. A reaction scheme in which two unidirectional substrate-driven reactions transfer high-affinity into low-affinity calcium-binding sites was applied to determine binding-volume increments. It has been inferred from the pressure dependence of the volume generating function, defined as the difference between the reciprocal reaction rates of the saturated and the unsaturated enzyme, that calcium binding proceeds in two steps. The two associated binding constants are endowed with large binding volume increments of opposite signs (+84 to +207 ml/mol and -3 to -136 ml/mol). Under different experimental conditions, with respect to the temperature, degree of calcium saturation and absence or presence of Me2SO, they add up to the same integral volume increment of 73 +/- 3.5 ml/mol for the entry of two calcium ions into the reaction cycle. In aqueous media, the two binding constants contribute about equally to binding and to the observed binding-volume increment. The presence of Me2SO strongly favours the first binding step. The size of the integral volume increment is in line with that determined for the interaction of calcium with calmodulin [Kupke, D.W. & Dorrier, T.E. (1986) Biochem. Biophys. Res. Commun. 38, 199-204]. PMID- 1761056 TI - The medium chains of the mammalian clathrin-associated proteins have a homolog in yeast. AB - We have cloned and sequenced mouse brain AP47, the medium chain of the trans Golgi network clathrin-associated protein complex AP-1. The predicted protein sequence of AP47 is closely related to rat and calf brain AP50, the corresponding medium chain of the plasma-membrane clathrin-associated protein complex AP-2. We have also identified in the yeast genome an open reading frame encoding a protein of previously unknown function. Referred to here as YAP54, its predicted protein sequence displays a striking homology to AP47. We therefore propose that Yap54 is the medium chain subunit of a putative AP-1 complex in yeast. From the analyses of the optimized sequence alignments of AP47, AP50 and Yap54p, we suggest a model for the domain organization of the medium chains. PMID- 1761057 TI - Expression and post-transcriptional regulation of ornithine decarboxylase during early Xenopus development. AB - In this paper we show that large changes in ornithine decarboxylase (ODC) activity occurred during early Xenopus development. Following fertilization, this enzyme activity rises with a quantitatively correlated accumulation of putrescine and spermidine. This increase in ODC activity was associated with an increased translation of the maternal ODC mRNA, which was stable in the embryo and whose polyadenylation increased slightly between fertilization and the mid-blastula transition (MBT). ODC activity was stable in cycloheximide-treated embryos, indicating that before the MBT this enzyme was not degraded. After the MBT, ODC activity fell, but no decrease in this mRNA was observed. In gastrulae, ODC mRNA was both increased in amount and polyadenylated. The reduced ODC activity at this stage of development was not associated with a fall in ribosome loading of the mRNA. Treatment of post-MBT embryos with cycloheximide lead to an accentuation of the normally observed decrease in ODC activity. Expression of Xenopus ODC in mutant ODC-deficient Chinese hamster ovary cells (C 55.7 cells) showed that the Xenopus enzyme was rapidly degraded and can be regulated post-translationally by polyamines, indicating that the post-MBT fall in ODC activity could be caused by a change in protein turnover or by polyamine-mediated regulation. PMID- 1761058 TI - Mollusc-specific toxins from the venom of Conus textile neovicarius. AB - Three peptide toxins exhibiting strong paralytic activity to molluscs, but with no paralytic effects on arthropods or vertebrates, were purified from the venom of the molluscivorous snail Conus textile neovicarius from the Red Sea. The amino acid sequences of these mollusc specific toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCI VLVCT (identical to the so called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGYCIVFVCT; TxIIA, WGGYSTYC gamma VDS gamma CCSDNCVRSYCT (gamma = gamma-carboxyglutamate). There is a similarity of the Cys framework of these toxins to that of the omega-conotoxins; however, their net negative charges, high content of hydrophobic residues and uneven number of Cys residues in TxIIA, are highly unusual for conotoxins. When assayed on isolated cultured Aplysia neurons, all three toxins induced membrane depolarization and spontaneous repetitive firing. The TxI toxins also induce a marked prolongation of the action potential duration, which is sodium dependent. These effects differ significantly from the blocking activities of piscivorous venom conotoxins. These mollusc specific conotoxins may therefore serve as new and selective probes for ion-channel functions in molluscan neuronal systems. PMID- 1761059 TI - Disulfide-bonded dimerization of fibronectin in vitro. AB - Human plasma fibronectin was denatured with 8 M urea and reduced with dithiothreitol. Dialysis or dilution of the solution led to formation of fibronectin dimers which migrated in non-reducing SDS/PAGE similarly to untreated control protein. When the redimerized fibronectin was reduced and re electrophoresed it formed a doublet of alpha and beta chains of equal intensity indicating that it was a heterodimer. Low concentrations (less than 1 mM) of Fe3+ enhanced the redimerization of fibronectin, suggesting that metal ions may mediate oxidative reactions in the formation of the disulfides. Consequently, redimerization of fibronectin was completely prevented by deferoxamine, an iron chelator. Dimerization of fibronectin took place most effectively at pH greater than or equal to 8.8 but decreased strongly at lower pH, representing more unfavourable conditions for the action of the thiolate anion in the thiol/disulfide exchange reaction. Redimerized fibronectin, however, lost many of its binding properties to macromolecular ligands, suggesting that the disulfide bonding did not entirely regenerate the proper conformation of the protein. Pulse/chase experiments of fibroblast cultures showed that the initially monomeric fibronectin was rapidly and quantitatively dimerized under conditions representing natural pH and environment. SDS/PAGE analysis of the dialyzed urea denatured/reduced thrombin and plasmin digests of fibronectin revealed that the NH2-terminal 30-kDa fragment and other fragments that contained intrachain disulfides quantitatively regained their non-reduced electrophoretic mobility. The results show that the dimerization and formation of intrachain disulfides of fibronectin may occur, in part, spontaneously, based on the amino acid sequence information of the protein. However, complete disulfide formation may also need other factors, present only in living cells, as suggested by pulse/chase experiments in fibroblasts. PMID- 1761060 TI - Temperature dependence of charge recombination from the P+QA- and P+QB- states in photosynthetic reaction centers isolated from the thermophilic bacterium Chloroflexus aurantiacus. AB - The temperature dependence of charge recombination from the P+QA- and from the P+QB- states produced by a flash was studied in reaction centers isolated from the photosynthetic thermophilic bacterium Chloroflexus aurantiacus. P designates the primary electron donor; QA and QB the primary and secondary quinone electron acceptors respectively. In QB-depleted reaction centers the rate constant (kAP) for P+QA- recombination was temperature independent between 0-50 degrees C (17.6 +/- 0.7 s-1 at pH 8 and pH 10). The same value was obtained in intact membranes in the presence of o-phenanthroline. Upon lowering the temperature from 250 K to 160 K, kAP increased by a factor of two and remained constant down to 80 K. The overall temperature dependence of kAP was consistent with an activationless process. Ubiquinone (UQ-3) and different types of menaquinone were used for QB reconstitution. In UQ-3 reconstituted reaction centers charge recombination was monoexponential (rate constant k = 0.18 +/- 0.03 s-1) and temperature independent between 5-40 degrees C. In contrast, in menaquinone-3- and menaquinone-4 reconstituted reaction centers P+ rereduction following a flash was markedly biphasic and temperature dependent. In menaquinone-6-reconstituted reaction centers a minor contribution from a third kinetic phase corresponding to P+QA- charge recombination was detected. Analysis of these kinetics and of the effects of the inhibitor o-phenanthroline at high temperature suggest that in detergent suspensions of menaquinone-reconstituted reaction centers a redox reaction removing electrons from the quinone acceptor complex competes with charge recombination. Instability of the semiquinone anions is more pronounced when QB is a short-chain menaquinone. From the temperature dependence of P+ decay the activation parameters for the P+QB- recombination and for the competing side oxidation of the reduced menaquinone acceptor have been derived. For both reactions the activation enthalpies and entropies change markedly with menaquinone chain length but counterbalance each other, resulting in activation free energies at ambient temperature independent of the menaquinone tail. When reaction centers are incorporated into phospholipid vesicles containing menaquinone-8 a temperature-dependent, monophasic, o-phenanthroline-sensitive recombination from the P+QB- state is observed, which is consistent with the formation of stable semiquinone anions. This result seems to indicate a proper QB functioning in the two-subunit reaction center isolated from Chlorflexus aurantiacus when the complex is inserted into a lipid bilayer. PMID- 1761061 TI - Primary structure and processing of the Candida tsukubaensis alpha-glucosidase. Homology with the rabbit intestinal sucrase-isomaltase complex and human lysosomal alpha-glucosidase. AB - The nucleotide sequence of a 4.39-kb DNA fragment encoding the alpha-glucosidase gene of Candida tsukubaensis is reported. The cloned gene contains a major open reading frame (ORF 1) which encodes the alpha-glucosidase as a single precursor polypeptide of 1070 amino acids with a predicted molecular mass of 119 kDa. N terminal amino acid sequence analysis of the individual subunits of the purified enzyme, expressed in the recombinant host Saccharomyces cerevisiae, confirmed that the alpha-glucosidase precursor is proteolytically processed by removal of an N-terminal signal peptide to yield the two peptide subunits 1 and 2, of molecular masses 63-65 kDa and 50-52 kDa, respectively. Both subunits are secreted by the heterologous host S. cerevisiae in a glycosylated form. Coincident with its efficient expression in the heterologous host, the C. tsukubaensis alpha-glucosidase gene contains many of the canonical features of highly expressed S. cerevisiae genes. There is considerable sequence similarity between C. tsukubaensis alpha-glucosidase, the rabbit sucrase-isomaltase complex (proSI) and human lysosomal acid alpha-glucosidase. The cloned DNA fragment from C. tsukubaensis contains a second open reading frame (ORF 2) which has the capacity to encode a polypeptide of 170 amino acids. The function and identity of the polypeptide encoded by ORF 2 is not known. PMID- 1761062 TI - Sequence-specific complex formation of DNA and a eukaryotic sequence-specific endonuclease, SceI. AB - Endo.SceI is a eukaryotic sequence-specific endonuclease of 120 kDa that causes sequence-specific double-stranded scission of DNA. Unlike results with restriction enzymes, we found a consensus sequence around the cleavage sites for Endo.SceI instead of a common sequence. We searched for conditions for studying the binding of Endo.SceI to DNA other than cutting. Under optimized conditions including gel mobility shift assay, Endo.SceI exhibited sequence-specific binding to a short double-stranded DNA (41 base pairs) containing a cleavage site and the DNA reisolated from the protein-DNA complex was not cleaved. The analysis of the complex of Endo.SceI and DNA isolated by the gel mobility shift experiments showed that the DNA-binding entity in the Endo.SceI preparation does have Endo.SceI activity and consists of an equal amount of 75-kDa and 50-kDa polypeptides. Based on this observation and those from previous studies, we conclude that Endo.SceI is a heterodimer of the 75-kDa and 50-kDa subunits. Under the present assay conditions, Endo.SceI did not show binding to single-stranded DNA having the same sequence of either plus or minus strand of the double stranded DNA containing the cleavage site (the 41-bp DNA). Endo.SceI showed significantly higher affinity for the consensus sequence than the major cleavage site in pBR322 DNA. Unlike the cleavage of DNA by Endo.SceI which requires Mg2+, this sequence-specific binding is independent of but stimulated by Mg2+. PMID- 1761063 TI - Purification and characterization of the cytosolic NADP(+)-dependent malic enzyme from human breast cancer cell line. AB - Cytosolic NADP(+)-dependent malic enzyme from a cultured human breast cancer cell line was purified to near homogeneity by two highly efficient chromatography systems: Pharmacia-LKB Q-Sepharose anion-exchange chromatography and adenosine 2',5'-bisphosphate-agarose affinity chromatography. The overall yield was 27%. The enzyme is presumably a tetramer composed of four probably identical subunits of Mr 65,000, which is similar to the enzyme from other sources. The pI and optimum reaction pH values for the tumor malic enzyme are 5.5 and 7.2, respectively. At pH 6.9, most of the enzyme exists as monomers. Activation energy for the enzyme-catalyzed oxidative-decarboxylation reaction is 57.4 kJ/mol. The enzyme is strictly NADP+ dependent, as NAD+ cannot support the oxidative decarboxylation reaction. ATP at low concentration inhibits the enzyme activity. Fumarate at concentrations up to 5 mM does not affect the enzymatic reaction rate. Therefore the tumor cytosolic malic enzyme, unlike the mitochondrial malic enzyme, is not an allosteric regulatory enzyme. PMID- 1761064 TI - The pharmaceutical physician--requirements for the position. AB - Physicians looking for a position as pharmaceutical physician are usually uncertain whether they are suitable for this activity by training and personal abilities. The main requirements are a major interest in therapeutics and research as well as the ability to treat a disease as an entity instead of the individual patient. The pharmaceutical physician is a specialist in the area of drug development. Even by treating populations and diseases his ultimate goal is to contribute to better care for the individual patient. Requirements for training and the personal abilities necessary for the position of a pharmaceutical physician are described and recommendations given for applicants. PMID- 1761065 TI - Influence of short term verapamil treatment on glucose metabolism in patients with non-insulin dependent diabetes mellitus. AB - The effect of a sustained-release verapamil preparation on glucose metabolism was investigated in 10 patients with non-insulin dependent diabetes mellitus. In a single blind cross-over study verapamil 240 mg b.d. for 1 week lowered fasting plasma glucose from a mean value of 11.6 mmol/l to 10.3 mmol.l-1, and the fasting glucose appearance rate was decreased from 1.5 to 1.2 mmol.min-1. The decrease in fasting plasma glucose and glucose appearance rate was not related to the steady state plasma concentration of verapamil, nor-verapamil and the metabolites D.617 and D.620. After oral glucose administration a tendency to lower plasma glucose values was found after verapamil administration. Plasma insulin, C-peptide, total and C-terminal glucagon were not significantly different in the placebo and the verapamil studies, neither in the fasting state nor after glucose. It is concluded that brief verapamil treatment decreases fasting plasma glucose and glucose turn-over in non-insulin dependent diabetics, possibly by inhibition of gluconeogenesis. PMID- 1761066 TI - Effects of captopril on diabetic nephropathy in hypertensive women. AB - The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng.ml-1.h-1, and so did serum potassium (from 4.57 to 4.83 mEq.1-1). Serum aldosterone fell from 161 to 70.9 pgm.ml-1 and from 27.3 to 15.3 micrograms.24 h-1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile. PMID- 1761067 TI - Effect of nifedipine on glucose potentiation of the acute insulin response to arginine in non-insulin-dependent diabetics. AB - The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic beta-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg.dl-1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P less than 0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM. PMID- 1761068 TI - Role of altered prednisolone-specific lymphocyte sensitivity in chronic renal failure as a pharmacodynamic marker of acute allograft rejection after kidney transplantation. AB - The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients. Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P less than 0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects. Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance. PMID- 1761069 TI - Diurnal variation of methotrexate disposition in children with acute leukaemia. AB - There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml.kg 1.min-1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml.min-1.kg-1 P less than 0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml.min-1.kg-1). Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance. PMID- 1761070 TI - Pharmacodynamics of ticlopidine in man in relation to plasma and blood cell concentration. AB - In 6 normal volunteers given single oral doses of 250,500 and 1000 mg ticlopidine (T), the peak plasma level of unchanged drug was reached after about 2 h. There was no correlation between the plasma T level and its inhibitory effect on platelet function, expressed as % inhibition of ADP-induced aggregation. By means of HPLC and GC/MS significant concentrations of T were demonstrated in washed red cells, platelets and neutrophils, with a marked difference in the time course of the appearance of cell-associated drug. The time course of platelet-associated T very accurately fitted that of the antiaggregatory activity. After subacute oral administration (250 mg b.d. for 7 days), the maximum effect on platelet function was observed after 3 to 4 days, when a significant concentration of platelet associated T had been reached. The pharmacological effect persisted as long as drug was detectable in platelet. An in vitro study strongly suggested that the antiaggregating effect was retained by treated washed platelets but not by treated plasma. It is suggested that the platelet compartment represents the pharmacological target of T via a specific uptake system. PMID- 1761071 TI - Drug-prescribing patterns in old age. A study of the impact of hospitalization on drug prescriptions and follow-up survey in patients 75 years and older. AB - A prospective drug surveillance study was undertaken in 300 elderly patients admitted to a geriatric clinic. Prescribing patterns were determined on admission, at discharge and 3.6 and 18 months after discharge. Patients referred from long-term care institutions were on significantly more drugs than non institutionalized subjects. A 34% reduction in the number of medicines prescribed at discharge was accompanied by a significant decrease in the mean number of prescriptions per patient, from 4.3 to 2.8, irrespective of whether the patient was institutionalized. Polypharmacy, defined by 5 or more concomitant drugs, declined from 43 to 17%. Dosage schedules were simplified in the majority of patients, as expressed by a significant decrease in the mean number of daily doses to be taken from 6.7 on admission to 4.4 at discharge. Cardiovascular drugs, diuretics and psychotropic drugs accounted for 64% of all drug prescriptions. At discharge, prescription frequencies were reduced for most medication categories, except diuretics and gastrointestinal drugs, which were being taken more often. The prescribing frequency of cardiac glycosides, the single most frequently prescribed drug class, decreased from 60 to 33% of the patients. Three months after discharge, prescribing patterns and frequencies were found to be very similar to the pre-admission situation. Eighteen months after discharge, overall drug use had increased by 15% compared to admission, and polypharmacy was recorded in 54% of patients. It is concluded that a substantial reduction in drug prescriptions was possible in the majority of elderly patients, particularly if they are institutionalized, on admission to a geriatric clinic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761072 TI - Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus. AB - Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism. PMID- 1761073 TI - Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa. AB - The clinical effects and pharmacokinetics of orally and intraduodenally administered levodopa, in four patients with Parkinson's disease have been compared. The patients had unpredictable fluctuations in motor function and episodic unresponsiveness to single doses of levodopa. The pharmacokinetic and clinical data of these patients were compared retrospectively with those of Parkinsonian patients with fluctuations in motor performance but with preserved clinical responses to single oral doses of levodopa. There was a threshold plasma concentration of levodopa associated with the "switch on or off" effect. In addition, rapid attainment of this critical plasma concentration was associated with a quicker onset of action and a more prolonged clinical response. All the patients had delayed absorption of levodopa related to delayed and erratic gastric emptying, which contributed to the fluctuation in motor response. In contrast, the patients with fluctuating motor effects but a preserved clinical response after levodopa showed an absorption pattern comparable to that of four patients studied after duodenal delivery of levodopa. It is suggested that there is a subgroup of patients with fluctuating responses due mainly to altered peripheral pharmacokinetics of levodopa. The findings demonstrate the relevance of routine measurements of plasma levodopa in patients with Parkinson's disease in whom there are fluctuations in motor performance. PMID- 1761074 TI - Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease. AB - We address, from a pharmacokinetic viewpoint, the important question of why some patients with clinical idiopathic Parkinson's disease experience a fall off in benefit from levodopa maintenance therapy. Thirteen such patients, of mean age 78 y, without overt fluctuations in motor control in temporal relation to dosing with a levodopa/decarboxylase inhibitor combination, were studied. Levodopa (currently 400 to 800 mg daily) had been started at between 61 and 81 y of age, the mean duration of therapy being 54 months. Plasma concentrations of levodopa and its peripheral metabolite, 3-0-methyldopa, were measured before a morning dose of levodopa (100 mg)/carbidopa (25 mg) and at hourly intervals for 6 h after. There was a significant negative regression between duration of levodopa therapy (but not age or severity of disease) and the area under the plasma concentration/time curve (AUC) for levodopa attributed to the test dose. A significant negative regression was also seen of duration of therapy on the dose absorbed per unit distribution volume, but not on the elimination rate constant, indicating a decrease in bioavailability and/or an increase in distribution volume with duration. There was a tendency for the plasma 3-0-methyldopa concentration, standardised for daily dose, [30MD], to increase with duration of therapy. Although, the regression of duration on [30MD] did not reach statistical significance, that on the ratio, [30 MD]/AUC, did so at the 0.01 level. The amount by, and time for which, the plasma levodopa concentration exceeds any critical threshold for the competitive active uptake process into the brain may thus decrease with duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761075 TI - Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease. AB - The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34 78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y. The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 mumol.l-1.min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml.min-1.kg-1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r = 0.474) and its plasma elimination half-life (r = 0.391), and was negatively correlated with clearance (r = -0.489). The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule. PMID- 1761076 TI - Quinidine but not quinine inhibits in man the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase. AB - Healthy male volunteers (n = 13) took a single oral dose of 60.3 mg of methoxyphenamine HCl with and without prior administration of either quinidine (250 mg as bisulphate salt) or its diastereomer quinine (300 mg as sulphate salt). Methoxyphenamine and its N-desmethyl, O-desmethyl and aromatic 5-hydroxy metabolites were quantified in the 0-32 h urine. The oxidative routes of methoxyphenamine metabolisms which had been previously shown to involve debrisoquine 4-hydroxylase, namely O-demethylation and 5-hydroxylation were both significantly inhibited by quinidine in the 12 extensive metabolizers. The inhibition was selective in that N-demethylation which does not involve this isozyme was not affected by quinidine. In all but one of these volunteers the methoxyphenamine/O-desmethylmethoxyphenamine ratio changed such that extensive metabolizers could be classified as poor metabolizers due to quinidine pretreatment. No marked change occurred in the renal excretion of methoxyphenamine and its three metabolites either in the extensive metabolizers because of quinine pretreatment or in the poor metabolizer because of treatment with either quinidine or quinine. Thus in the extensive metabolizer phenotype it was demonstrated in one study that enzyme inhibition of quinidine was selective in terms of the metabolic pathways inhibited as well as stereoselective with respect to the inhibitor. PMID- 1761077 TI - Comparison of in vitro and in vivo biotransformation in patients with liver disease of differing severity. AB - The activity of 7-ethoxycoumarin O-deethylase (ECOD) has been measured in liver biopsy samples from 23 patients (smokers and non-smokers) with different degrees of structural liver damage. The results, which reflect in vitro cytochrome P450 dependent biotransformation, were correlated with various measures of the P450 dependent in vivo elimination of caffeine and metamizol. The relatively non specific, low affinity component of ECOD activity was significantly correlated with the kinetics of metamizol (mean residence time, apparent clearance, half life, area under the concentration-time curve, and metabolite excretion in the urine). Thus, metamizol elimination, which is mainly due to P450 IIB, and the low affinity component of ECOD both reflect, at least in part, the activity of the same form of P450. In contrast, caffeine biotransformation, which is via P450 IA, was not correlated with ECOD activity. There was no relation between the kinetics of metamizol and caffeine, perhaps because of the inducing effect that smoking has on caffeine elimination. In patients with liver disease, smoking appears to alter the elimination of caffeine more than the degree of liver disease. PMID- 1761078 TI - Enantioselective steady-state kinetics of unbound disopyramide and its dealkylated metabolite in man. AB - Disopyramide is provided as a racemic mixture of R and S enantiomers, which have different pharmacodynamic and pharmacokinetic characteristics. Five volunteers were given racemic disopyramide 100 mg and 200 mg t.d.s. in a cross-over design. Plasma and urine concentrations of disopyramide and its active metabolite monodesisopropyl-disopyramide (MND) were determined at steady state by an enantioselective HPLC method. Unbound drug in plasma was measured after ultrafiltration. There was enantioselective clearance of unbound disopyramide (0.39 l.h-1.kg-1 for R-disopyramide and 0.58 l.h-1.kg-1 for S-disopyramide after 100 mg t.d.s.). The enantioselectivity was due to differences in the metabolism of disopyramide to MND and in further non-renal clearance, and the renal clearance of disopyramide was not enantioselective. The in vivo protein binding of disopyramide, which was saturable for both enantiomers, was also enantioselective. The difference in binding of the two enantiomers was explained by a difference in apparent binding capacity rather than in apparent binding affinity. The renal clearance of S-MND was significantly higher than R-MND (0.29 and 0.19 l.h-1.kg-1, respectively, after 100 mg t.d.s.). The renal clearance of MND also showed a tendency to saturation at higher concentrations. PMID- 1761079 TI - Dose-proportionality of eltoprazine. Pharmacokinetics of single oral doses in healthy subjects. AB - Eltoprazine. HCl belongs to a new class of psychotropic drug, the serenics. The dose-proportionality and pharmacokinetics of eltoprazine HCl has been investigated after single oral doses of 5, 10, 20 mg (18 subjects) and 30 mg (12 subjects) in a partly randomized, cross-over design. Eltoprazine was well tolerated and there were no relevant changes in safety parameters. All subjects showed irregular plasma-concentration-time profiles, some subjects demonstrating secondary peaks. The mean half-life was calculated to be about 6.5 h. The renal excretion of eltoprazine was characterized by net tubular secretion. AUC, peak plasma concentrations and the amount excreted unchanged in the urine were linearly related to the dose. Renal clearance and t1/2 were independent of dose. Thus, eltoprazine HCl was well tolerated orally and exhibited a linear pharmacokinetic profile. PMID- 1761080 TI - Drug prescription in young children: results of a survey in France. Epicreche Research Group. AB - A 8.5-month prospective study was performed in the Rhone area of France to study the incidence of infectious diseases in children in day care, and the qualitative and quantitative aspects of drug prescriptions for young children. The families of 1.359 children agreed to participate (98.5% of those selected). During the follow-up period 3.605 infections episodes were reported and 10.706 medications were used, an average of 3.0 medications per episode. Antibiotics were used in the treatment of 2.333 infectious episodes (65%) amoxycillin (36%), cephalosporin (23%), macrolide (17%) and trimethoprim-sulphamethoxazole (9%). Acetylsalicylic acid and paracetamol were used 865- and 1.568-times, respectively. Drugs with multi-active components represented 11.3% of the total number of systemic medicines reported. Paracetamol was prescribed in 59% of cases in a multi-active component drug, whereas this type of product accounted for 83.5% of the antihistamines (used 932-times). The rationale behind the paediatric prescribing habits of French medical doctors is discussed in relation to results previously obtained in other European countries. PMID- 1761081 TI - Relation between plasma concentration and clinical efficacy after sublingual single dose apomorphine in Parkinson's disease. AB - Five patients with Parkinson's disease were given a single sublingual dose of apomorphine in 3 mg tablets (2 patients received 18 mg and 3 patients took 39 mg). The therapeutic effect appeared within 33.0 min and lasted 137 min. There was a significant correlation between peak concentration, area under the curve, dose (mg/kg) and the duration of the therapeutic effect. PMID- 1761082 TI - Pharmacokinetics of oral salbutamol controlled-release in Asian patients with asthma. AB - Using a double blind, double dummy crossover design, single dose and steady state pharmacokinetics of oral controlled release (SCR) salbutamol 4 mg and 8 mg tablets b.d. has been studied in 8 Asian patients. Plasma salbutamol was measured over 12 h. In 8 patients the single dose mean Cmax was 4.2 ng.ml-1 and 7.7 ng.ml 1 after 4 and 8 mg, respectively. In 5 patients the steady state mean Cmax, Cmin and tmax were 8.1 ng.ml-1 and 4.7 ng.ml-1 and 6 h for the 4 mg tablets and 14.1 ng.ml-1 and 7.1 ng.ml-1 and 4 h for the 8 mg tablets. It is concluded that both doses of SCR show features of controlled release and that they produced a relatively constant plasma level of salbutamol in Asian patients. PMID- 1761083 TI - Effects of parenteral diclofenac sodium on upper gastrointestinal motility after food in man. AB - In experimental animal models nonsteroidal anti-inflammatory drugs may influence gastrointestinal motility, but as evidence is lacking in man. The effect of diclofenac sodium 75 mg i.m. on the motor response of the upper gastrointestinal tract to food has been studied by manometry in 9 healthy volunteers. Diclofenac had no effect on the motor activity of the stomach, duodenum, or jejunum after a 605 kcal meal. PMID- 1761084 TI - Pharmacokinetics of flumazenil in fulminant hepatic failure. PMID- 1761085 TI - Effect of flomoxef on human platelet aggregation. PMID- 1761086 TI - Inhibitory substantia nigra inputs to the pedunculopontine neurons. AB - Responses of 43 pedunculopontine area (PPN area) neurons to electrical stimulation of the substantia nigra (SN) were studied in anesthetized rats. An intracellular recording technique was used to demonstrate that SN stimulation evoked hyperpolarizing potentials, which were identified by intracellular injections as inhibitory postsynaptic potentials (IPSPs). These IPSPs were often followed by a rebound depolarization that originates several spike potentials. These IPSPs were characterized as monosynaptic, with latencies varying from 1.0 to 8.5 ms. Similar results were observed in some animals with chronic unilateral coronal lesion just rostral to subthalamic nucleus (STH), which severed the rostral afferents. PPN are neurons were also antidromically activated by SN stimulation. Two PPN area projection neurons were clearly identified. Mean latency of one group was 0.71 ms; mean latency of the second group was 5.16 ms. The morphological analysis of a neuron inhibited by SN stimulation and labeled with horseradish peroxidase (HRP) demonstrated that the soma was fusiform in shape, with the axon originating in the soma and collaterals and a large dendritic field extending in the ventrodorsalis direction. The results indicate that the PPN area is reciprocally connected with the SN, which elicits an inhibitory effect on PPN area neurons. PMID- 1761087 TI - Binocular neuronal responsiveness in Clare-Bishop cortex of Siamese cats. AB - Retinotopy and binocular responsiveness were studied extracellularly in a total of 278, 61, 110 and 275 cells sampled in areas 17, 18, 19 and Clare-Bishop (CB) of Siamese cats. The misalignment of the visual axes of the two eyes was determined by the pupil reflex method in the behaving animal. The recording sessions were conducted under N2O anesthesia, supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo) and muscle relaxants (Gallamine triethiodide) using two types of visual stimulators presenting two dimensional (2D) motion stimuli and the visual cues for three-dimensional (3D) motion. All of the nine Siamese cats demonstrated Boston type retinotopic abnormalities in all of cortical areas 17-19 and CB. Very few binocular cells were present in areas 17-19 and the posterior (A1-P2) CB but they were numerous in most of CB (A9-4). A significant fraction (36/78) of binocular cells in the major CB of the Siamese cats demonstrated similar response selectivity to that reported in normal CB cortex for stimulation with the 3D motion cues under both null disparity and strabismic conditions (binocular receptive fields for two eyes were optically superposed or separated by the strabismic angles estimated in the individual animals). These findings indicate that the binocular signals converging to the CB cells through different pathways (signals coming from the contralateral eye via the ipsilateral hemisphere including the interlaminar nucleus and areas 17-19, and commissural signals from the ipsilateral eye via the contralateral areas 17-19 and CB) were integrated to yield useful information for the recognition of 3D motion, and that the major CB is an actual site of binocular integration at least in Siamese cats, rather than being merely a reflection of the information processing before the CB cortex. PMID- 1761088 TI - Corticofugal modulation of the information processing in the auditory thalamus of the cat. AB - Single unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity. PMID- 1761089 TI - Intrinsic inter- and intralaminar connections and their relationship to the tonotopic map in cat primary auditory cortex. AB - Small iontophoretic injections of the lectin, Phaseolus vulgaris leucoagglutinin (PHA-L), were made into different layers of the primary auditory cortex (AI) of cats. Injections in layer I labeled two types of morphologically distinct fibers in layer I as well as a smaller number of axons in layers II and III. Layer II injections labeled descending axons that produced a dense plexus of terminal fibers in layers I-III of both AI and adjacent auditory fields. Injections in layer III also labeled a dense plexus of axon collaterals at the junction of layers V and VI and labeled patches of terminal fibers in both AI and adjacent auditory fields. These were densest in layers I-III but usually extended into layers IV and V as well. The patches were partly formed by axon collaterals of layer III pyramidal cells that traveled for over 4 mm in the gray matter. Injections confined to layer IV labeled axons in all layers of the cortex but none of these axons appeared to reach the white matter. The axons spread laterally in layer IV and up into the superficial layers and ramified especially layer I. Injections in layers V and VI labeled axons in all layers' of the cortex but these were densest in the deep layers where labeling was fairly homogeneous. In the upper layers the labeling was arranged in semi-discrete patches. Large injections involving layers I-III were studied in tangential sections. Between 3 and 8 patches of terminal labeling were observed in AI and these were mainly arranged in a band with its long axis aligned approximately in the dorsoventral direction. However dense patches of terminal labeling also occurred both anterior and posterior to the injection site. In selected experiments portions of the tonotopic map in AI were mapped by single unit recording and subsequently the map was related to patches of anterogradely labeled fibers that surrounded injections of PHA-L. Rows of dorsoventrally oriented patches were among cells with a similar best frequency to those in the injection site. However patches located anterior or posterior to the injection site were among cells with higher or lower best frequencies. Two injections of PHA-L close together produce different patterns of labeling. One of the injections usually produces one or more patches that has no correlate among the patches of fibers labeled by the adjacent injection. This is clearest when one of the injections is made with biotinylated PHA-L that can be visualized directly without the use of primary antibodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761090 TI - Adaptation and habituation of the vestibulo-ocular reflex in intact and inferior olive-lesioned rats. AB - The gain of the vestibulo-ocular reflex (VOR) of intact pigmented rats was adaptively modified by training protocols that created a visual-vestibular conflict. For training, head restrained animals were oscillated on a turntable in front of an optokinetic pattern projected onto a cylindrical wall. The optokinetic pattern either moved the same amplitude with the animal ("in-phase": 0.05 Hz +/- 20 degrees/s) or opposite in direction ("out-of-phase": turntable and pattern 0.05 Hz +/- 10 degrees/s each). VOR responses were tested in darkness before and after each 8 min training period for a duration of 40 min. During "out of-phase" training the gain of compensatory eye movements measured in light was close to 2 from the beginning on and the VOR tested in darkness increased in gain progressively from 0.48 (+/- 0.12) to 0.9 (+/- 0.3; P less than 0.05) in 5 out of 7 rats. Two rats did not adapt their VOR gain. Phase values decreased slightly by about 10 degrees. During "in-phase" stimulation compensatory eye movements were almost completely suppressed (gain close to 0) from the beginning on and the VOR tested in darkness decreased gradually in gain from 0.62 (+/- 0.17) to 0.13 (+/- 0.1; P less than 0.001) in all 6 trained rats. Phase values decreased in parallel from 151 degrees to 119 degrees (P less than 0.01). The effectiveness of the "in phase" training paradigm in the absence of compensatory eye movements indicates that retinal image slip is the relevant signal for adaptation. In seven rats with histologically verified almost complete inferior olive (IO) lesions (chemically induced at least 45 days prior to training), "out-of-phase" and "in-phase" stimulation evoked compensatory eye movements with gains comparable to those in intact rats. VOR parameters measured in darkness were altered with respect to those of control rats. Gain differed extremely between individuals and phase lag re acceleration was in all IO-lesioned rats larger than in intact rats. The time constant of the VOR in response to table velocity steps was significantly longer (17 s +/- 4) than in intact rats (11 s +/- 3). Training did not alter the gain of the VOR in 5 out of 7 IO-lesioned rats. One rat increased its gain during "out-of phase" training in the first, but not during a second training session (and not during "in-phase" training) and another rat decreased its gain during "in-phase" training (but not during "out-of-phase" training).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761091 TI - Different effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells. AB - A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal ganglion cells of adult rats by recording the retinal responses to patterned stimuli (pattern electroretinogram) after unilateral section of the optic nerve at two different levels: intraorbital and intracranial. The results show that the site of lesion of the optic nerve affects the time of disappearance of the pattern electroretinogram. The pattern electroretinogram takes longer to be degraded after an intracranial section than an intraorbital section. PMID- 1761092 TI - Effects of cingulate cortical lesions on avoidance learning and training-induced unit activity in rabbits. AB - This study extends an ongoing analysis of the neural mediation of discriminative avoidance learning in rabbits. Electrolytic lesions encompassing anterior and posterior cingulate cortex (area 24 and 29) or ibotenic acid lesions in area 24 only were made prior to avoidance conditioning wherein rabbits learned to step in response to a tone conditional stimulus (CS+) in order to avoid a brief, response terminated 1.5 mA. foot-shock unconditional stimulus (US). The US was presented 5 s after CS+ onset, in the absence of a prior stepping response. The rabbits also learned to ignore a different tone (CS-) not followed by the US. Multi-unit activity of the caudate and medial dorsal (MD) thalamic nuclei, projection targets of the cingulate cortex, was recorded during learning in all rabbits. Activity was also recorded in area 29 in the rabbits with area 24 lesions. Learning in rabbits with combined lesions was severely impaired and it was moderately retarded after lesions in area 24. MD thalamic and caudate training induced neuronal discharge increments elicited by the CS+ were enhanced in rabbits with lesions, suggesting a suppressive influence of cingulate cortical projections on this activity. Early-, but not late-developing training-induced unit activity in area 29c/d was absent in rabbits with area 24 lesions, indicating that area 24 is a source of early-developing area 29 plasticity. These results are consistent with hypotheses of a theoretical working model, stating that: a) learning depends on the integrity of two functional systems, a mnemonic recency system comprised by circuitry involving area 24 and the MD nucleus and a mnemonic primacy system comprised by circuitry involving area 29 and the anterior thalamic nuclei; b) corticothalamic information flow in these systems suppresses thalamic CS elicited activity in trained rabbits; c) corticostriatal information flow is involved in avoidance response initiation. An absence of rhythmic theta like neuronal bursts in area 29b in rabbits with area 24 lesions is attributable to passing fiber damage. PMID- 1761093 TI - Role of the nucleus geniculatus lateralis ventralis (GLv) in the optokinetic reflex: a lesion study in the pigeon. AB - Several functions have been proposed for the avian GLv (color vision, pupillary reflex, optomotor mechanisms). In the present paper we have examined the role of the GLv in optomotor responses. For this purpose, horizontal and vertical optokinetic nystagmus (OKN) were quantified in response to different stimulation velocities, before and after chemical (kainic acid) lesions. Unilateral lesion of the GLv produced a marked increase of the horizontal OKN gain when the eye contralateral to the lesion was stimulated in the temporonasal (T-N) direction and, to a lesser extent, when the ipsilateral eye was stimulated in the naso temporal (N-T) direction. Biocular integration was reduced after the lesion, since the biocular stimulation corresponding to these two monocular stimulations (ipsiversive to the lesion) produced only a moderate gain increase. When stimulations were delivered in the opposite direction (contraversive to the lesion), the horizontal OKN gain was slightly increased for the N-T monocular stimulation of the eye contralateral to the lesion, but was unchanged for other stimulations. A bilateral lesion of the GLv provoked only a slight increase of the horizontal OKN gain. The vertical OKN was not affected by the GLv lesions. Thus, the GLv system is probably involved in the modulation of optomotor responses and could mediate visuo-optokinetic interactions, each nucleus (and its associated system) exerting an inhibitory (or disfacilitatory) effect on the horizontal OKN in one direction. PMID- 1761094 TI - A neuronal correlate of spatial stability during periods of self-induced visual motion. AB - Motion of background visual images across the retina during slow tracking eye movements is usually not consciously perceived so long as the retinal image motion results entirely from the voluntary slow eye movement (otherwise the surround would appear to move during pursuit eye movements). To address the question of where in the brain such filtering might occur, the responses of cells in 3 visuo-cortical areas of macaque monkeys were compared when retinal image motion of background images was caused by object motion as opposed to a pursuit eye movement. While almost all cells in areas V4 and MT responded indiscriminately to retinal image motion arising from any source, most of those recorded in the dorsal zone of area MST (MSTd), as well as a smaller proportion in lateral MST (MST1), responded preferentially to externally-induced motion and only weakly or not at all to self-induced visual motion. Such cells preserve visuo-spatial stability during low-velocity voluntary eye movements and could contribute to the process of providing consistent spatial orientation regardless of whether the eyes are moving or stationary. PMID- 1761095 TI - Amygdalectomy and ventromedial prefrontal ablation produce similar deficits in food choice and in simple object discrimination learning for an unseen reward. AB - Cynomolgus monkeys (Macaca fascicularis) with either bilateral amygdalectomy or bilateral ventromedial prefrontal cortical ablations showed abnormal choices between apple, lemon, olive, and meat. Not only did they choose meat or olive more often than normal animals, but also their choices were less consistent from trial to trial than the normal animals' choices were. The same animals were subsequently tested for their ability to learn 2-choice simultaneous visual discriminations between objects which they could suck. The positive object yielded fruit juice, which entered the mouth directly without being seen. Both groups of animals with lesions were severely impaired in this discrimination learning task. The reason why amygdalectomy has little effect on simple object discrimination learning in the Wisconsin General Test Apparatus, we suggest, is that the animal can there associate the visual discriminanda with the visual properties of the food reward, a mechanism which is not available when the reward is unseen. These results add to existing evidence of a close functional relationship between the amygdala and the ventromedial prefrontal cortex, and they support the proposal, derived from previous work, that the amygdala is important for associating visual stimuli with the incentive value of reinforcers. PMID- 1761096 TI - A quantitative analysis of pallidal discharge during targeted reaching movement in the monkey. AB - Neurons in the globus pallidus have been studied during reaching movements of the arm made at varying speeds. The reaching task is similar to one used in earlier experiments, in which disruption of normal pallidal output caused changes in movement time. The pallidal cells studied were those that showed task-related changes in activity and a modification of discharge when the arm was manipulated outside of the task. Neuronal discharge was assessed to evaluate two possible models, one in which the timing of task-related discharge varied as a function of movement time and the other in which the amplitude (mean firing rate) of the change in discharge varied as movement time varied. The relation between neuronal discharge and movement time was examined quantitatively on a trial-by-trial basis using a statistical algorithm that identified each phase of the change in neuronal discharge on each trial. A non-parametric statistic was used to determine the correlation between movement time and the duration or latency of changes in neural firing or the mean discharge during each phase of the cell's response. For fifty-five percent of the 40 neurons studied, the timing of the cell's response (duration or latency) varied as a function of movement time. For only 10 cells (25%) was there a significant correlation between movement time and the mean firing rate during one or more phases of the cell's response. Both timing and frequency modulation with movement time were limited to cells responsive to manipulation at the wrist or the shoulder. PMID- 1761097 TI - The role of the subthalamic nucleus in the response of globus pallidus neurons to stimulation of the prelimbic and agranular frontal cortices in rats. AB - We investigated how the cerebral cortex can influence the globus pallidus by two routes: the larger, net inhibitory route through the neostriatum and the separate, smaller, net excitatory route through the subthalamic nucleus. Stimulation (0.3 and 0.7 mA) of two regions of frontal agranular (motor) cortex and of the medial orbitofrontal cortex centered in the prelimbic cortex typically elicited one or more of the following extracellularly recorded responses in over 50% of tested cells: an initial excitation (approximately 6 ms latency), a short inhibition (15 ms latency) and a late excitation (29 ms latency). Some other cells responded with an excitatory response only (18 ms latency). The excitatory responses largely arise from the subthalamic route. Kainic acid or electrolytic lesion of the subthalamic nucleus eliminated most excitatory responses and greatly prolonged the duration (16 vs 50 ms) of the inhibition. Subthalamic neurons typically showed one or more of the following responses to cortical stimulation: an early excitatory response (4 ms latency), an inhibitory period (9 ms) and a late excitatory response (16 ms). The early response was seen after motor cortex but not prelimbic stimulation. The timing of the globus pallidus and subthalamic responses suggest the operation of a reciprocal inhibitory/excitatory pathway. Two reciprocal interactions were indicated. First, pallidal inhibition may disinhibit the subthalamus and, via a feedback pathway onto the same pallidal cells, act to terminate the neostriatal-induced inhibition. Second, there may be a feedforward pathway from pallidal cells to subthalamic neurons to a different group of pallidal cells. This pathway could act to suppress competing responses. Thus the subthalamus may have three actions: 1) an early direct cortical and 2,3) later reciprocal feedforward and feedback excitatory antagonism of the neostriatal mediated inhibition of globus pallidus. PMID- 1761098 TI - Tactile discrimination of curvature by humans using only cutaneous information from the fingerpads. AB - Spherically curved surfaces were applied, with controlled force, to the fingerpads of human subjects; their fingers were immobilized. The curvature of the surfaces was characterised by the reciprocal of the radius of curvature. In scaling experiments, the subjects' perceived magnitude of curvature increased markedly with an increase in the curvature of the stimulus. An increase in contact force resulted in a slight decrease in perceived curvature. Four discrimination experiments were performed using a forced choice paradigm. Subjects could discriminate, at the 75% level, a flat surface (zero curvature) from a convex curvature of 4.9 m-1 (radius of curvature 204 mm) and from a concave curvature of 5.4 m-1 (radius 185 mm). When discriminating 2 convex spherical surfaces, subjects could discriminate a curvature of 144 m-1 from a curvature of 158 m-1 (radii 6.95 and 6.33 mm respectively), and could discriminate a curvature of 287 m-1 from one of 319 m-1 (radii 3.48 and 3.13 mm respectively); the Weber fraction is about 0.1. Contact areas between the curved surfaces and the fingerpad skin were estimated. There was approximate correspondence between contact areas and the scaling functions. PMID- 1761099 TI - Comments to: S.D. Newlands and A.A. Perachio: Neuronal activity in the medial vestibular nuclei following unilateral labyrinthectomy. PMID- 1761100 TI - Some new aspects of CJD epidemiology in Slovakia. AB - Descriptive epidemiological and genealogical data obtained by prospective and retrospective studies on CJD in Slovakia and in patients emigrating from CJD clusters were analysed. Observations contradictory to an exclusively genetic etiology of temporo-spatial accumulation of CJD are presented. Data indicating a genetically increased susceptibility to the disease and its coincidence with environmental risk in clustering patients are discussed. PMID- 1761101 TI - "Clusters" of CJD in Slovakia: the first statistically significant temporo spatial accumulations of rural cases. AB - A space-time analysis of clustering among 78 definite CJD cases who died in Slovakia (75) and an adjacent part of Hungary (3) during 1972-1991 is presented. Two geographical rural accumulations of sporadic and familial CJD patients in the north and south of Central Slovakia were found. There was evidence of two significant clusters when spatial and temporal neighborhoods were defined by distances of 2,4,5 and 7 km within 1.5 and 2 years. Involvement of genetic mechanisms in the clusters was demonstrated, and the possible role of environmental (zoonotic) risk factors are considered. PMID- 1761102 TI - Creutzfeldt-Jakob disease in the last 5 years in Hungary. PMID- 1761103 TI - Epidemiological surveillance of Creutzfeldt-Jakob disease in the United Kingdom. AB - Systematic epidemiological surveillance of Creutzfeldt-Jakob disease was carried out in England and Wales covering the years 1970-1984. The results of this work provide a basis from which to assess any change in the pattern of Creutzfeldt Jakob disease following the occurrence of Bovine Spongiform Encephalopathy. The methodology, early results and problems of the current systematic national survey of CJD, initiated in May 1990, are discussed. PMID- 1761104 TI - Risk of Creutzfeldt-Jakob disease in relation to animal spongiform encephalopathies: a collaborative study in Europe. AB - This paper describes a study of the risk of Creutzfeldt-Jakob disease in various European countries. The objectives of the study are to investigate the frequency of Creutzfeldt-Jakob disease and other human spongiform encephalopathies in Europe in relation to animal spongiform encephalopathies, and to assess the risk of Creutzfeldt-Jakob disease in relation to genetic, occupational and nutritional factors. The study will consist of three parts: the establishment of registries of Creutzfeldt-Jakob disease on the basis of cases in the registries, and molecular genetic studies with material collected in the registries. PMID- 1761105 TI - Focal accumulation of CJD in Slovakia: retrospective investigation of a new rural familial cluster. PMID- 1761106 TI - Creutzfeldt-Jakob disease among Libyan Jews. AB - The focus of CJD among Jews of Libyan origin has been recognized for two decades, but the reasons underlying it were unknown. Prevailing views suggested transmission from sheep infected with scrapie. However, recent data show that in fact CJD in this ethnic group is a genetically determined disease due to a point mutation on the codon 200 of the prion protein gene. The clinical characteristics of CJD in this group, and particularly the less common periodic activity in the EEG, are reviewed. New findings include peripheral neuropathy of the demyelinating type in two cases, presumably due to involvement of Schwann cells. The pathophysiology of the disease includes, presumably, a focal post translational modification of the prior protein, (predisposed by the mutation). Later, the disease progresses through cell-to-cell transmission. PMID- 1761107 TI - Creutzfeldt-Jakob disease in young people. AB - Three neuropathologically confirmed cases of Creutzfeldt-Jakob disease in young people (19, 23, and 27 years of age) are described. None had received pituitary hormone therapy. At the onset of illness all patients were suspected of having SSPE or other viral encephalitis, because of the similarity of clinical symptomatology and the shift towards older age of SSPE onsets observed in Poland in recent years. PMID- 1761108 TI - Creutzfeldt-Jakob disease--clinical picture analysis. AB - The early, late, and terminal features of (CJD) were analyzed, based on the clinical histories and picture evolution of 12 histologically-confirmed cases of CJD. The most essential features observed were sensorimotor disintegration, and impairment of both mental and higher cortical functions, occurring in various combinations. On the basis of a sampling of early symptoms and signs we were able to make an early differential diagnosis. PMID- 1761109 TI - "Clusters" of CJD in Slovakia: the first laboratory evidence of scrapie. AB - Epidemic-like occurrence of Creutzfeldt-Jakob disease was observed in 1987 in Slovakia (Orava). Search for the cause of CJD focus indicated a coincidence of genetic and environmental risks in clustering patients. Since Spongiform Encephalopathies might be transmitted orally, (Bovine Spongiform Encephalopathy), the possibility of zoonotic source of CJD cases in Orava was also considered. A deficient knowledge about the occurrence of scrapie in Slovakia stimulated an examination of sheep with signs of CNS disorders in two flocks of Valasky breed in Orava. In one flock, neurohistopathological examination revealed in sheep brains lesions characteristic for scrapie. Frozen brain tissue of these animals were used for the detection of scrapie associated fibrils. They were found in 2 animals from the same flock. This is the first laboratory confirmation of scrapie in Czecho-Slovakia. The possible epidemiological and economical implications are emphasized. PMID- 1761110 TI - Slow neurological diseases (scrapie and visna) of the sheep in the USSR. PMID- 1761111 TI - Some problems of diagnosis of the spongiform encephalopathies in ruminants. AB - The difficulties of a positive diagnosis in the spongiform encephalopathies based only on epidemiological and clinical data are briefly reviewed. However, in B.S.E. as in scrapie, the epidemiology and the clinical data may frequently suggest these diseases. The main diseases which must be taken into account in the differential diagnosis of both spongiform encephalopathies are discussed and the criteria of the differential diagnosis are tabulated. PMID- 1761112 TI - Bovine spongiform encephalopathy (BSE): the current situation and research. AB - Bovine spongiform encephalopathy (BSE), discovered in Great Britain in 1986, was to pose one of the most serious threats to the well-being of the British cattle industry this century. The disease is now established as a member of the group of diseases known as the sub-acute spongiform encephalopathies caused by unconventional, transmissible agents and which includes scrapie of sheep. It is from scrapie of sheep that it appears BSE has resulted though it is possible BSE may have existed in a sub-clinical form in cattle. The vehicle of transmission is meat and bone meal prepared from infected ruminant carcases and included in the protein concentrate rations of cattle, especially dairy cattle in which the disease predominates. Most animals become exposed as calves and the incubation period is typically 4-5 years with most cases occurring at this age. The increase in exposure of cattle to infection that resulted in disease in 1985/1986 was 1981/1982. The factors that contributed to this increase were an increasing sheep population, possibly an increase in the prevalence of scrapie and changes in the industrial processing of animal waste to prepare meat and bone meal. The clinical signs of BSE include abnormal behaviour, posture, gait and an increased sensitivity to visual and aural stimuli. There is loss of condition and milk yield. In only one of 28,197 cases of BSE confirmed by 10 May 1991 can feed be almost certainly ruled out as a source of infection. This therefore may be a singleton case of maternal transmission though we cannot be certain. Every other case so far has been exposed to meat and bone meal in the diet and thus resulted in an extended common source epidemic. A large research programme is underway to investigate the epidemiology, clinicopathology, transmission and molecular biological/genetic aspects of the disease. Much is collaborative between Institutes and Member States of the European Community, in which the disease, as in Britain, is notifiable. In Britain the lynch pin of control for animal health has been the ban established in July 1988 on feeling of ruminant protein to ruminant animals. Though there is no evidence that either BSE or scrapie is a hazard to humans, as a precautionary measure, suspect animals are compulsorily slaughtered and destroyed (except all brains are taken for diagnosis) with compensation being paid at 100% of value. Milk from such animals is also destroyed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761113 TI - Mechanism of the damage to myelinated axons in experimental Creutzfeldt-Jakob disease in mice: an ultrastructural study. AB - We report the ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD). Initially the myelin sheath was separated into several concentric bands, and cellular processes penetrated between layers of myelin and lifted away the outermost lamella. Then a complicated labyrinth of the concentric cellular processes, clearly belonging to either astrocytes or macrophages, invested myelinated axons. In terminal stages axons completely denuded of myelin were seen in the center of concentric networks of cellular processes. Myelin remnants were seen within astrocytes and macrophages. We conclude that the mechanism(s) of damage to myelinated axons in CJD may be similar to that operating in immunologically mediated demyelinating disorders. PMID- 1761114 TI - Tubulovesicular structures in human and experimental Creutzfeldt-Jakob disease. AB - Tubulovesicular structures (TVS) have been consistently observed in brain tissue of animals with transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy, and experimental Creutzfeldt-Jakob disease (CJD). In this communication we demonstrate for the first time the presence of TVS in natural CJD. TVS were detected in all 3 CJD specimens. However, they were rare and were found only in one or two locations per grid. They were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter, and they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of spongiform encephalopathies irrespective of the affected host and the strain of infectious agent emphasizes their biological significance. PMID- 1761115 TI - Experimental drug treatment of scrapie: a pathogenetic basis for rationale therapeutics. AB - Pharmacological treatment with polyanions or amphotericin B in hamsters with experimental scrapie reveals that it is possible to delay the appearance of the disease only when the drug is given before the invasion of the agent into the clinical target areas of the brain. We suggest such early treatment may be possible for individuals at high risk of acquiring the disease, such as healthy mutation-positive relatives of patients with familial Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome, or recipients of potentially contaminated pituitary-extracted human growth hormone. PMID- 1761116 TI - Transmissible spongiform encephalopathies (TSE) virus-induced amyloidoses of the central nervous system (CNS). PMID- 1761117 TI - Hemopoietic improvement following fetal liver infusion in aplastic anemia. AB - 41 (38 males, 3 females) patients with aplastic anemia received fetal liver infusion (FLI) from 74 abortuses with gestation periods of 8-32 (Median(M)-16) weeks and cell dose of 0.004-11.1 x 10(8) (M-2.3 x 10(8)) from September, 1976 until November, 1987. 35 persons received single FLI; those with recurrence or no response received two or more FLI. 8 received two; 7, three; 2, four; and 1, six FLI. There was a slow and incomplete autologous hematopoietic improvement in 40% and expected survival of 52% at 1 year, 45% at 2 yr, and 37% at 5 yr (Kaplan Meier estimate). There was rise in fetal hemoglobin (Hb), 0-15.7%, (M-3.5) among responders in 3-20 (M-6) months. Patients who survived for more than 12 months had, on average, a longer duration of disease (4 months or more), and higher granulocyte and platelet counts. Statistically, however, these differences were not significant. Reticulocyte count was significantly lower in those who survived beyond 12 months. 1 patient developed acute undifferentiated leukemia 3 yr post FLI. The study indicates that fetal liver infusion is likely to benefit about 40% of individuals suffering from severe aplastic anemia. Longer surviving patients, however, may be at risk of developing clonal diseases. PMID- 1761118 TI - Has the incidence of multiple myeloma in old age been underestimated? The myeloma project of health region I in Norway. I. AB - All patients in the region with newly discovered M components were registered from 15 Aug. 1984-31 Dec. 1986. Among a total of 393 patients enrolled, 162 had multiple myeloma (MM). The incidence rate was 6.6 per 100,000 population per year (age-adjusted to the European standard population), which is somewhat higher than previous reports based on hospital and autopsy records. In particular, the incidence rate was higher in the greater than 70 age group. Thus, the median age was 72 yr, which is the highest reported. As many as 71 (44%) of the 162 MM patients were asymptomatic; these asymptomatic patients had the same age distribution as the symptomatic ones. The stage distribution, occurrence of risk factors, response to chemotherapy, response duration and survival were similar in the age groups below and above the median and, in multivariate survival analysis, age was not an independent risk factor. PMID- 1761119 TI - Incidence and follow-up of asymptomatic multiple myeloma. The myeloma project of health region I in Norway. II. AB - During a general population follow-up study in Health Region I in Norway, 162 patients with multiple myeloma (MM) were diagnosed. 71 of these (44%) were asymptomatic, and were observed without chemotherapy. The great majority (90%) were in stage I, and there were only 2 with light chain disease. 45 of the 71 asymptomatic patients developed progressive disease during the 4-5 year follow-up period. Estimated median time to disease progression was 26 months. The presence at diagnosis of osteolytic lesions and/or at least 20% plasma cells in the bone marrow defined a group with significantly shorter time to progression (median 10 vs 39 months). Median survival from diagnosis for the asymptomatic patients was 45 months, which is significantly longer than the 26 months of the symptomatic group. However, when estimated from the start of treatment, the survival was similar for the two groups. PMID- 1761120 TI - An Arg545----Cys545 substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease. AB - Type IIB is a special variant of von Willebrand's disease, characterized by an abnormal von Willebrand factor which shows an increased interaction with platelets. This interaction sometimes causes platelet aggregation and thrombocytopenia in vivo. It involves the glycoprotein-Ib (GPIb) receptor on platelets and corresponding GPIb-binding sites in the von Willebrand factor. We here demonstrate a C----T mutation at codon 1308 of the von Willebrand factor gene in 2 related patients with IIB von Willebrand's disease. The transition gives rise to a substitution of arginine by cysteine at position 545 of the mature von Willebrand factor subunit. This position is close to the GPIb- as well as the collagen- and heparin-binding domains of the von Willebrand factor. The mutation may change the conformation of the molecule in this region and activate the GPIb-binding domain, which is normally not exposed in the von Willebrand factor of circulating blood. PMID- 1761121 TI - Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. AB - Veno-occlusive disease (VOD) is a major cause of toxic death after autologous bone marrow transplantation (ABMT). We studied the potential role of continuous administration of low-dose heparin for VOD prevention in 234 consecutive patients who underwent ABMT in our institution. The population consisted of 98 patients autografted before October 1984 who did not receive heparin, and a series of 136 patients autografted from October 1984 to March 1989 containing 98 patients included in a randomized trial comparing heparin administration (n = 52) vs no heparin (n = 46), and an additional group of 38 patients who received non randomized heparin in view of high-risk criteria to develop VOD (n = 31) or other reasons unrelated to VOD (n = 7). Overall, 90 patients (38%) received heparin and 144 (62%) did not. The global incidence of VOD was 13/234 (5-5%). Heparin did not reduce the risk of VOD in all subgroups studied. In particular, in the randomized trial, the incidence of VOD was 2.2% in the group without heparin vs 7-7% in the group receiving heparin. We analyzed in depth the 13 patients who developed VOD and we compared them to a control group of 13 patients pair-matched for age, sex, diagnosis and preparative regimen, who did not develop VOD. We found that abnormal LFT before ABMT predisposed patients to VOD; refractoriness to platelet transfusion was observed in 85% of the patients in the VOD group vs 15% in the control group (p less than 0.05). VOD patients had an increased requirement for red cells and platelet transfusions, a lower recovery (R less than 25%) after the second and third platelet transfusion, and shorter intervals separating the first four platelet transfusions. Further, the platelet reconstitution after ABMT in the VOD group was slower in comparison to the control group (p less than 0.01). Again, in this pair-matched analysis continuous infusion of low-dose heparin did not prevent VOD. PMID- 1761122 TI - Treatment of myelodysplastic syndromes with recombinant human erythropoietin. AB - 12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses. PMID- 1761123 TI - Diagnostic utility of the pre-incubated acidified glycerol lysis test in haemolytic and non-haemolytic anaemias. AB - The usefulness of the pre-incubated acidified glycerol lysis test (AGLT), a laboratory test for spherocytosis, has been investigated in a selected hospital population of 348 patients with haemolytic and non-haemolytic anaemia. The AGLT was positive in 58 out of 59 patients with hereditary spherocytosis. In all 32 patients with other types of hereditary haemolytic anaemia the AGLT was normal or equivocal, but clearly different from spherocytosis. Adults with a positive AGLT, but without hereditary spherocytosis, had auto-immune haemolytic anaemia, myelodysplastic syndrome or were pregnant women. In newborn infants the AGLT was positive, in the first week of life, in those babies having hereditary spherocytosis or immune haemolysis due to blood group incompatibility; no positive AGLT results were seen if no haematological explanation for neonatal hyperbilirubinaemia could be found. At the optimal cut-off point the sensitivity of the AGLT for hereditary spherocytosis was 98.3% and the specificity 91.1%, under the most unfavourable conditions. The AGLT is a very useful and simple test for the diagnosis of hereditary spherocytosis. PMID- 1761124 TI - Acute lymphoblastic leukaemia relapsing in bowel. PMID- 1761125 TI - Signal-averaged electrocardiography. PMID- 1761126 TI - The health care gap for women. PMID- 1761127 TI - Strategies for developing a family support group. AB - Various interventions may be used by nurses to provide social support to critical care families. Nurses may support family members in one-to-one relationships, or by facilitating the development of supportive relationships in the group setting. The steps described here are fundamental in developing a support group for family members of adults hospitalized in a surgical ICU to meet their predetermined needs. The support needs of family members and the timing of a support group during the critical care phase must first be validated. Once this assessment is completed, the support group may be based on the educational model, mutual-peer support model, educational-mutual support model, or ventilation model. The group model selected will provide direction to the structure, membership, and leadership of the support group. Regardless of the model considered appropriate for the needs of the family population and setting, critical care nurses need to evaluate the impact of the support group on the psychologic health of the family. The four different group perspectives clearly illustrate the need for nurses to determine what types of support are needed or are most beneficial for families during various phases of illness. Perhaps family members benefit from sharing and camaraderie during the acute or critical care phase, whereas educational support groups are more effective in reviewing illness and treatment implications after the immediate threat of the illness has passed. Findings from these evaluation studies will assist nurses in shaping intervention strategies for critical care family members in clinical practice. PMID- 1761128 TI - Health care trends: a call for advanced knowledge and skills in baccalaureate graduates. PMID- 1761129 TI - Denying alcoholism. PMID- 1761130 TI - Applying standards of care in legal proceedings. PMID- 1761131 TI - From hopeful to hopeless ... when do we write "do not resuscitate"? AB - The issue of do not resuscitate (DNR) decisions has been the subject of much discussion in the medical literature. To try to understand the factors that may be determinants of the timing of DNR decisions, we reviewed the charts of 70 consecutive burned patients who died between 1986 and 1988. When a DNR decision was written, it was within 48 hours of the patient's death (74% of patients). No statistical difference was found in the sex distribution or in the percentage of body surface area burned in the DNR group and in the resuscitation group. Physicians, nurses, social workers, the hospital attorney, the district attorney, and the coroner of our county were interviewed. The uncertainty of legal guidelines and practical considerations of family expectations preclude a uniform approach to this problem. PMID- 1761132 TI - Identification and treatment of acute myocardial infarction by electrocardiographic site classification. AB - The nature and severity of an acute myocardial infarction may be related to the region of myocardial involvement. Four possible sites of infarction are inferior, anterior, posterior, and lateral. Knowledge of ECG tracings common to each of these areas, the coronary artery source of each, clinical complications, and signs and symptoms is vital to subsequent nursing management. PMID- 1761133 TI - The art and science of weaning from mechanical ventilation. PMID- 1761134 TI - Using multiple teaching techniques in a continuing education program. AB - The use of Gregorc's mind mediation channel theories as a framework for continuing education planning has been successful and well received by participants on the basis of evaluation responses received over a 2-year period. This framework has been especially applicable in the setting described because participants form a heterogeneous audience drawn from registered nurses in various practice settings at many different institutions across the country. Integration of various techniques designed to meet the needs of participants with different mind mediation characteristics assures that participants will find at least one technique targeted to their learning needs. In a more homogeneous setting with a consistent audience for continuing education (for example, a critical care unit with monthly continuing educational offerings), the planner may want to consider asking participants (staff nurses) to complete the Gregorc Style Delineator so that educational experiences can be planned for congruency with participants' learning characteristics. PMID- 1761135 TI - Update: are milking and stripping chest tubes necessary? PMID- 1761136 TI - Neuromuscular blockade. PMID- 1761137 TI - The gift. PMID- 1761138 TI - [The effects of body fat distribution on glucose tolerance in overweight subjects: glucose intolerance and insulin resistance induced by intra-abdominal fat accumulation]. AB - To evaluate the pathophysiological significance of intra-abdominal fat accumulation in Japanese subjects with mild to moderate overweight, 107 subjects (56 men and 51 women, aged 16-68 years) with body mass index (BMI, kg/m2) of 17 39 (mean +/- SD, 25 +/- 4.3) were evaluated. Subjects with disorders which affect glucose metabolism, such as thyroid, adrenal, liver, and kidney diseases, were excluded. A 75 g oral glucose tolerance test (OGTT) was performed in all subjects, and venous samples were obtained before 15, 30, 60, 90 and 120 min after the glucose load for plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) measurements. In 72 of the subjects, plasma free fatty acid (FFA) level at fasting was also determined. The degree of visceral fat accumulation was evaluated using a CT-scan by the method reported by Fujioka et al. (Metabolism, 36: 54-59, 1987), and intra-abdominal fat area/subcutaneous fat area (V/S ratio) was obtained. V/S ratio and BMI correlated positively in subjects with BMI less than 25 (17 men and 16 women, aged 28-62 years) but they did not correlate at all with each other in those with BMI greater than or equal to 25 (39 men and 35 women, aged 16-68 years). Based on this finding, the possible adverse effects of increased intra-abdominal fat on glucose metabolism were investigated in the subjects with BMI greater than or equal to 25. For this purpose, the correlation of V/S ratio with fasting PG (FPG), fasting IRI (FIRI), fasting CPR (FCPR), FPG/FIRI, FFA, or PG area (sigma PG) and sigma PG/sigma IRI at OGTT was analyzed. V/S ratio positively correlated with FPG, sigma PG, FPG/FIRI and sigma PG/sigma IRI but not with FFA. The correlation between V/S ratio and FIRI or FCPR was significant in the subjects with V/S ratio greater than or equal to 0.8 in men and greater than or equal to 0.4 in women. In sharp contrast to V/S ratio, BMI did not correlate at all with any of these metabolic indices. We conclude that in Japanese subjects with mild overweight to moderate obesity, intra-abdominal fat accumulation, but not the increase in the degree of obesity, accompanies worsening of glucose tolerance. Because PG elevation relative to IRI secretion is progressively greater with increasing V/S ratio, it is suggested that the deleterious effects of intra-abdominal fat accumulation can be attributed to increased insulin resistance. PMID- 1761139 TI - [The influence of the sympathetic nervous system on brown adipose tissue: an experimental and histopathologic study on aging]. AB - Brown adipose tissue (BAT) is known to be a principal energy source of non shivering thermogenesis and related diet-induced thermogenesis. These regulate body temperature and body weight and are controlled by the dissipation of excessive dietary caloric intake. We carried out histopathologic, immunohistochemical and biochemical studies of BAT in rats in relation to aging changes. Four groups of Donryu strain male rats (5 each of 1 month, 2 months, 4 months and 20 months of age) were used. They had been given commercial chow and tap water ad libitum and were kept in an air-conditioned room. Body weight (BW), interscapular BAT weight (IBATW) and g IBATW/g BW of rats were measured. Nor adrenalin (NA), and dopamine-beta-hydroxylase (DBH) of IBAT were determined. To evaluate the catecholaminergic effects of BAT, morphometric quantitation of BAT was carried out based on the cytoplasmic locularity of fat globules in the BAT cells. Distribution of DBH in BAT was assessed immunohistochemically by the avidin biotin peroxidase complex method. With the use of statistical analysis of variance procedure, there were highly significant decreases in the ratio of g IBATW/g BW (p less than 0.0001) and in the concentrations of NA (p less than 0.0001) and DBH (p less than 0.01) between young (weaning at 1 month old) rats and adult (aged from 4 to 20 months) rats. In the morphometric measurement, by the statistical analysis system (SAS) Spearman correlation coefficient method, there was a significant increase of Type 5 cell (monocular brown adipose tissue cell) in 4 month and 20 month rats, compared to 1 month and 2 month rats (p less than 0.05). Immunohistochemical study of BAT showed localization of DBH in perivascular mesenchymal cells which corresponded with the morphologic distribution of catecholamine as reported by Lever. The results suggest that in the processes of aging in the rat there are reductions in the ratio of g IBATW/g BW, NA and the activity in DBH. PMID- 1761140 TI - [Clinical studies on 3 pairs of monozygotic twin sisters affected by Graves' disease]. AB - Clinical studies were undertaken of three pairs of monozygotic twin sisters affected by Graves' disease. The evidence that the twins were monozygotic was established by similarity in physical appearance, identical blood-group antigens and identical HLA types. All pairs were female, and the evidence of Graves' disease in both members of the pair was observed in 2 out of 3 pairs. In the remaining pair the disease started in the elder sister, but the younger sister still remained in euthyroidism in spite of the presence of diffuse goiter. The disease occurred in the second decade in all the patients, and the interval between the occurrence of the disease in twin sisters was 1 to 4 years. No common specific type of HLA was found among all three pairs, but DR4 was common in two pairs of twin sisters showing positive MCHA test. Serum TRAb was positive in 2 pairs of twin sisters but negative in the remaining one. However, it became positive in the elder sister of the latter pair during the antithyroid treatment. The effect of antithyroid drug treatment was found to be similar in each of the twin sisters, and the serum TRAb moved almost in parallel with serum FT4 level. These results indicate that a genetic factor may be of great importance in the aetiology of Graves' disease, and there was a strong preponderance for it to occur in women and the second decade was the peak age for its occurrence. The common specific type of HLA for all Graves' patients was not found in this study. A strong relationship was observed between Grave's disease and TRAb. PMID- 1761141 TI - [The role of the renal dopaminergic and the prostaglandin systems in renal uric acid metabolism in patients with essential hypertension]. AB - The present study aimed to elucidate the role of renal dopaminergic and prostaglandin (PG) systems in renal uric acid metabolism in essential hypertension. Mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), serum uric acid (SUA), urinary excretions of uric acid (UUAV) and sodium (UNaV), fractional excretions of uric acid (FEUA) and sodium (FENa), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before and after intravenous injection of a dopamine receptor antagonist, metoclopramide (MCP: 8 mg/m2.BSA), or before and after a single oral administration of prostaglandin synthesis inhibitor, indomethacin (IM: 75 mg), in 34 mild-to-moderate essential hypertensives (EHT). MCP injection or acute oral administration of IM caused significant decreases of UNaV and FENa in each group, whereas MAP, HR and SUA did not change in either group. Significant decreases in Ccr, UUAV and FEUA and increases in PRA and PAC were demonstrated by MCP injection, while no significant changes in these parameters were revealed by IM administration. There was a significant positive correlation between delta UUAV and delta Ccr or delta FEUA in both groups. In addition, a close positive correlation between delta UUAV and delta UNaV as well as between delta FEUA and delta FENa was found in the MCP group, but not in the IM group. On the other hand, no significant correlation was observed between delta UUAV and delta PRA or delta PAC in either MCP or IM administration. The decreases of UUAV and FEUA were significantly greater in MCP than in IM administration, despite similar changes in Ccr, UNaV and FENa between the two procedures. These data suggest that the endogenous renal dopaminergic system may contribute to renal uric acid metabolism, which is rather closely related to sodium handling in essential hypertension than the prostaglandin system. Furthermore, the attenuated renal dopaminergic activity may contribute to the elevation of serum uric acid level in patients with essential hypertension. PMID- 1761142 TI - [Immunohistochemical studies on the thyroid C-cells in primary hyperparathyroidism]. AB - This study was conducted in order to establish whether C cells, which are responsible for secretion of calcitonin within the thyroid gland, change either in volume or morphology under conditions of chronic hypercalcemia in primary hyperparathyroidism. Out of 106 primary hyperparathyroid patients undergoing surgery, in 11 cases the thyroids were excised and examined for changes in the C cell. As a control group we used thyroids removed in another 14 cases undergoing thyroidectomy or laryngectomy. Calcitonin in the C cell was observed by optical microscope after immuno staining using the indirect peroxidase-labeled antibody technique. C cells are not evenly distributed within the thyroid. However, there is excellent positive correlation (p less than 0.001) between the C-cell index, which is the average of two tissue samples excised from the area at the border between the upper 1/3 and middle 1/3 of the thyroid lobe (the area where most C cells are found), and the total number of C cells. The C-cell index can thus be used as an indicator of the total number of C cells in the thyroid. The number of C cells decreased (p less than 0.01) as the level of calcium in serum increased. In patients with primary hyperparathyroidism, this decrease in C cells was significantly greater (p less than 0.025) than in the controls. Focal C cell hyperplasia and diffuse C cell hyperplasia were present in both the control group and primary hyperparathyroid group, but there was no significant difference between the two groups as to the frequency of occurrence. For both these conditions the rate of occurrence was considered within normal ranges for C cell morphology. We concluded that the decrease in C-cell count in primary hyperparathyroidism patients with chronic hypercalcemia is due to consumption of calcitonin in the C cell. PMID- 1761143 TI - Glycogen structure and biogenesis. PMID- 1761144 TI - Comparative biochemistry of vitamin B12 (cobalamin) metabolism: biochemical diversity in the systems for intracellular cobalamin transfer and synthesis of the coenzymes. PMID- 1761145 TI - Regulation of neutrophil and macrophage production by growth factors. PMID- 1761146 TI - Hepatoprotective agent (+)-cyanidanol increases the synthetic phase of hepatocellular regeneration. AB - 1. (+)-Cyanidanol (250 mg/kg) administration to male rats resulted in a concentration-dependent increase in [3H]-thymidine incorporation into hepatic nuclear DNA as well as a corresponding increase in the per cent of labelled cells. 2. The increase in [3H]-thymidine incorporation and per cent labelled cells was significant by 24 hr, maximal between 48 and 96 hr, and declined very slowly to normal by 15 days (360 hr). 3. Administration of (+)-cyanidanol resulted in an increase in heptic putrescine levels and ornithine decarboxylase activity at 6 hr but not at 24 hr. However, S-adenosylmethionine decarboxylase and spermidine acetyltransferase activities were unaltered. 4. Inspite of these favorable conditions, for cell division, mitotic index (per cent cells in metaphase) was not increased by (+)-cyanidanol. 5. These results along with previous findings indicate that (+)-cyanidanol stimulates the S-phase activity of hepatocellular regeneration, but the commitment to M-phase depends on the occurrence of liver injury. PMID- 1761147 TI - Conformational stability of citraconylated ovalbumin. AB - The lysine residues were modified to varying degrees (50-91%) with citraconic anhydride to determine the extent of conformational change in ovalbumin. Major findings included: 1. Sixteen of the 20 lysine residues are located on the protein surface, while the remaining four are buried. 2. The tertiary structure changed progressively with the degree of modification. 3. However, the secondary structure was disrupted only after one or more of the four buried lysines had been citraconylated. 4. Although the secondary structure was unaltered, the alpha helix was nevertheless progressively destabilized as the surface 16 lysine residues were modified. This destabilization was due to electrostatic repulsions introduced by the entering citraconyl groups. PMID- 1761148 TI - Comparison of the metabolic fate and tissue distribution of B700, an albumin-like melanoma-specific antigen with serum albumin in normal and tumor-bearing mice. AB - 1. B700, a murine melanoma antigen, is a member of the serum albumin protein family, being closely related to murine serum albumin (MSA). 2. We have studied and compared the metabolic fate and anatomic distribution of radioiodinated B700 and MSA administered to semisyngeneic naive and tumor-bearing mice. 3. Labelled material from both proteins is excreted primarily into urine. 4. The rate of excretion of the two proteins is markedly different, with B700 having a shorter half-life in the body. 5. Despite their similar molecular weights, intact B700 represents approx. 30% of the radioactivity in the urine but only 4% of the MSA in the urine is intact. 6. These studies demonstrate that the host can readily distinguish between very similar normal (MSA) and tumor-associated (B700) molecules and process them differently. 7. Similar findings of differential fate and distribution have been reported in comparing other albuminoid molecules [Dueland S., Blomhoff R. and Pedersen J. I. (1990) Biochem. J. 267, 721-725]. PMID- 1761149 TI - Enhancement of immunogenic properties of ovalbumin as a result of its chlorination. AB - 1. Chlorination of ovalbumin results in its enhanced immunogenic properties. 2. This has been evaluated by the interleukin-2 production after incubation of the modified protein with antigen presenting cells and T helper cells. PMID- 1761150 TI - Characterization of the process of 5-aminolevulinic acid formation from glutamate via the C5 pathway in Clostridium thermoaceticum. AB - 1. In vitro formation of 5-aminolevulinic acid (ALA) from glutamate required two enzyme fractions, separable on Blue Sepharose affinity chromatography, and a tRNA fraction, which can be replaced by Escherichia coli tRNA(Glu) in the reconstituted assay. 2. Gabaculine was shown to inhibit ALA formation in the complete assay as well as in a defined system consisting of only glutamate-1 semialdehyde and the enzyme fraction not retained on Blue Sepharose. 3. The results indicate that the enzyme system supporting ALA formation in Clostridium thermoaceticum is very similar to the tRNA(Glu)-dependent C5 pathway in plant plastids. PMID- 1761151 TI - Inhibition by monochloramine of the transport of glutamine and glucose in HeLa cells and lymphocytes. AB - 1. Chloramine was previously shown to inhibit glutamine uptake by human lymphoblast tumour cells. In the present study, the effect of monochloramine on the glutamine and glucose transport systems in HeLa cells and rat mesenteric lymphocytes was investigated. 2. Initial exposure to monochloramine slightly inhibited both the glutamine and glucose transport systems in HeLa cells. However, pre-exposing the cells to monochloramine increased its inhibitory action. 3. Similar results were obtained using rat mesenteric lymphocytes, which suggests that monochloramine's effects are not cell specific. 4. Only the Na(+) independent (system L) component of glutamine transport activity in HeLa cells was inhibited by monochloramine. 5. Dithiothreitol protected both the glucose and glutamine transport carriers in HeLa cells against monochloramine inhibition. 6. Monochloramine did not inhibit HeLa cell metabolism, nor enhance cell lysis, which, in conjunction with other experimental data, suggests that monochloramine inhibits cellular transport activity by binding to thiol groups present on the membrane. PMID- 1761152 TI - In vitro metabolism of [14C]4-chlorobiphenyl and [14C]2,2',5,5' tetrachlorobiphenyl by hepatic microsomes from rats and pigeons. Evidence against an obligatory arene oxide in aromatic hydroxylation reactions. AB - 1. The catalytic activities of cytochromes P-450IA1 and P-450IIB1 in control and Aroclor 1254 treated rats and pigeons (1 mmol/kg) were assessed using [14C]4 chloro- and [14C]2,2',5,5'-tetrachlorobiphenyl as substrates. Treatment of rats resulted in increases of the total amount of chloroform-extractable metabolites of [14C]4-chlorobiphenyl from 37.2 (control) to 199.4 and 221.6 nmol/hr per mg microsomal protein at 48 and 120 hr post treatment. The portion of [14C]4-chloro 3',4'-dihydroxybiphenyl (M4) and of a second unidentified dihydroxylated metabolite (M3) increased during these incubations from 13.7% for controls to 53.5% at 48 hr and 69.12% at 120 hr post treatment. 2. [14C]4-chloro-3' hydroxybiphenyl (M1) and [14C]4-chloro-4'-hydroxybiphenyl (M2) were the major metabolites formed by pigeon hepatic microsomes; however, the amounts formed were 38.7- and 29.3-fold less, respectively, than in untreated rats. Treatment of pigeons with Aroclor 1254 increased the metabolite formation from 1.0 (control) to 13.6 and 22.4 nmol/hr per mg microsomal protein at 48 hr and 120 hr post treatment respectively; however, only small amounts of metabolites M3 (0.5 nmol/hr per mg protein) and M4 (2.0 nmol/hr per mg protein) were detected. 3. Treatment of rats with Aroclor 1254 resulted in an approximately two-fold increase in the rate of metabolism of [14C]2,2',5,5'-tetrachlorobiphenyl, and the ratio of 3- to 4-hydroxylation increased from 0.45 (control) to 0.6 and 0.8 at 48 hr and 120 hr post treatment respectively. The rate of metabolism of [14C]2,2',5,5'-tetrachlorobiphenyl by control and Aroclor 1254 treated pigeons was up to 23-fold lower than in rats and there was no evidence for the formation of the diol metabolite M3. However, as with rats, the ratio of meta- to para carbon atom hydroxylation increased from 0.58 (controls) to 0.72 at 120 hr post treatment. 4. From the evidence presented, it is suggested that cytochromes P 450IA1 and P-450IIB1 may not metabolize PCB-congeneric substrates via an obligatory arene oxide intermediate. PMID- 1761153 TI - Twenty-four-hour changes of S-adenosylmethionine, S-adenosylhomocysteine adenosine and their metabolizing enzymes in rat liver; possible physiological significance in phospholipid methylation. AB - 1. The metabolic control of adenosine concentration in the rat liver through the 24-hr cycle is related to the activity of adenosine-metabolizing enzymes [5' nucleotidase (5'N), adenosine deaminase (A.D.), adenosine kinase (A.K.) and S adenosylhomocysteine hydrolase (SAH-H)]. 2. Two peaks of adenosine were observed, one at 12:00 hr caused by high activity of 5'N and SAH-H, and the other at 02:00 hr, caused by a decrease in purine catabolism and purine utilization, low activity of SAH-H and de novo purine formation. 3. The similarity of the adenosine and S-adenosylmethionine (SAM) profiles through the 24-hr cycle suggests a role of adenosine in transmethylation reactions, because, during the night (02:00 hr), the metabolic conditions favor the formation and accumulation of S-adenosylhomocysteine (SAH), with consequent inhibition of transmethylation reactions. 4. In the 24-hr variation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), the lowest ratio of PC/PE was observed at 24:00 02:00 hr when SAH concentration is high, whereas the highest PC/PE ratio occurs at the same time as one of the SAM/SAH ratio maxima. PMID- 1761154 TI - Al-ATP as an intracellular carrier of Al(III) ion. AB - 1. Using 27Al and 31P NMR spectroscopy in conjunction with an Al lactate aqueous reagent at pH 7.2, Al complexes of ATP and of phospholipids were characterized in synthetic-aqueous and organic-phospholipid chemical systems and in the intact human red blood cell. 2. The observed 31P NMR chemical shifts of the Al-ATP complex in aqueous laboratory preparations or the intact human red blood cell were, respectively, alpha phosphate, -11.53 delta; beta phosphate, -22.65 delta; and gamma phosphate, -10.95 delta. 3. The observed complexed 27Al chemical shift was -2.22 delta. 4. The relative affinities for Al of the phospholipids determined from 31P NMR spectroscopic titrations were PA much greater than Cl much greater than PS greater than PG approximately equal to PI greater than PE plus approximately equal to PE much greater than SPH greater than PC. PMID- 1761155 TI - Steroid hormone receptors in the thymus: a site of immunomodulatory action of melatonin. AB - 1. Melatonin and glucocorticoids are known to affect the immune response in an opposite mode. The probability for an interaction between these hormones in the thymus gland has been investigated in rats following chronic administration of exogenous melatonin and long-term exposure to variable levels of circulating glucocorticoids. 2. Daily melatonin administration was shown to affect the properties of corticosterone and progestin receptors in the thymus in the presence of normal and increased systemic corticosterone concentrations, but not in adrenalectomized animals. 3. In intact rats melatonin caused a marked increase in the affinity and a decrease in the density of thymic receptors for adrenal steroids. Following corticosterone overdosage, simultaneously with melatonin treatment, a decrease in receptor affinity and a relative increase in the number of binding sites was observed. 4. The results suggest that steroid hormone receptors in the thymus might be considered as a target site for the interaction between melatonin and adrenal steroids in the modulation of the immune response. PMID- 1761156 TI - Melatonin effects on thymus steroid receptors in the course of primary antibody responses: significance of circulating glucocorticoid levels. AB - 1. The effects of chronic melatonin treatment on antibody production and thymus glucocorticoid and progestin binding sites in the course of primary immune response were investigated in rats subjected to long-term manipulations of circulating glucocorticoid concentrations. 2. The chronic melatonin treatment enhanced the PFC-ability in control and ADX animals and decreased it in the presence of high circulating corticosterone levels. 3. Melatonin treatment increased the affinity and decreased the density of glucocorticoid and progestin receptors in non-immunized animals, while in SRBC-primed rats it was ineffective. 4. The influence of melatonin was apparent when steroid environment was subject of variations: it decreased the affinity of both types of receptors in ADX animals and increased it in immunized rats which have been subjected simultaneously to corticosterone overdose. PMID- 1761157 TI - Heterogeneity of synaptosomal membrane preparations from different regions of calf brain studied by partitioning and counter-current distribution. AB - 1. Membranes obtained by lysis and Yeda-press treatment of synaptosomes (nerve endings) from cortex, caudateus nucleus, and hippocampal region of calf brain have been studied by partitioning within a liquid-liquid aqueous two-phase system consisting of water, dextran, Ficoll, and poly(ethylene glycol). 2. The partitioning of membranes was sensitive to the presence of a dextran-bound dye, Procion yellow HE-3G, in the lower phase. 3. The two-phase system was used for counter-current distribution to study the heterogeneity of the synaptic membranes from the three regions of the brain and to separate the membranes into fractions. 4. The obtained counter-current distribution profiles strongly depended on the region of the brain from which the membranes were isolated. 5. The membrane fractions obtained showed marked differences in their SDS electrophoresis pattern. PMID- 1761158 TI - Regulation of basement membrane invasiveness in human breast cancer model systems. PMID- 1761159 TI - Regulation of thyroid follicular volume by bidirectional transepithelial ion transport. AB - Previous studies have shown that thyroid cells in monolayer culture exhibit bidirectional ion transport comprising apical-to-basal amiloride-sensitive Na+ transport and oppositely directed bumetanide-sensitive Cl- transport. We have now investigated the role of ion transport in the regulation of thyroid follicular size using follicular primary porcine thyroid cell cultures. Bumetanide (10 microM) added at the beginning of culture inhibited the formation of follicular lumina and caused a fall in follicle height when added to 3-day-old cultures. In contrast, phenamil (1 microM; an amiloride analog) increased follicle size both in freshly isolated and 3-day-old cultures. The effect of bumetanide was prevented by the prior addition of phenamil. Micropuncture studies showed that follicles had a lumen-negative, basal-positive transepithelial potential difference which was progressively reduced in magnitude by the serial addition of bumetanide (10 microM) and phenamil (1 microM). We conclude that thyroid follicles possess a bidirectional ion transport system which transports Na+ in an apical-to-basal direction and Cl- in the opposite direction. The balance between these two processes determines net solute flux and hence follicular size. A physiological role of ion transport in the thyroid may be to regulate follicular volume suggesting that abnormalities of ion transport may be responsible for disorders of follicular size. PMID- 1761160 TI - Sertoli cells are the site of interleukin-1 alpha synthesis in rat testis. AB - To elucidate the cellular origin of interleukin-1 (IL-1) in the mammalian testis, we assayed IL-1 activity in culture media of Sertoli cells collected from rats at 20, 35 and 45 days of age as well as in culture media of interstitial, peritubular and germ cells from adult rats. IL-1 was detected in Sertoli cell culture media isolated from 35- and 45-day-old rats. At 45 days approximately twice as much IL-1 was produced than at 35 days. In contrast, IL-1 activity was not detected in 20-day-old rat Sertoli cell culture media nor in interstitial, peritubular and germ cell culture media. The Sertoli cell IL-1 activity was specifically neutralized by an IL-1 alpha antiserum. It is concluded that Sertoli cells produce IL-1 alpha and that this production increases during sexual maturation. PMID- 1761161 TI - Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation. AB - Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell. PMID- 1761162 TI - Inhibitory effects of serum and stimulatory effects of estrogen on prolactin mRNA levels in GH3 rat pituitary tumor cells. AB - We investigated the effects of serum and estrogen on prolactin (PRL) mRNA accumulation in GH3 cells under different cell culture conditions. Hybridization analysis of GH3 cellular RNA indicated that PRL mRNA levels decreased more than 20-fold in cells cultured for 1 week in medium containing dextran-charcoal treated serum (stripped serum). No effects on actin mRNA levels were observed under these conditions. Furthermore, this inhibition of PRL mRNA accumulation depended on the concentration of stripped serum in the medium. Although incubation in stripped-serum medium inhibited cell growth, these culture conditions did not appear to irreversibly affect the GH3 cell population. These data indicate that a potent inhibitor of PRL mRNA accumulation is present in stripped serum. GH3 cells grown in stripped-serum medium were shown to be responsive to estrogen. Treatment of these cells with 10(-9) M estradiol resulted in a 6.6-fold stimulation of PRL gene expression. However, estrogen had no effect on cell growth under these conditions, suggesting that estrogen stimulates PRL gene expression and cell proliferation by independent mechanisms. PMID- 1761163 TI - Growth and cell cycle regulation of mRNA levels in GH3 cells. AB - In the rat anterior pituitary gland, estrogen increases both prolactin (PRL) mRNA levels and stimulates the proliferation of PRL-producing cells. The temporal sequence of these events suggests that PRL gene expression may be coordinated with cell proliferation. We investigated the relationship between cell cycle progression and the accumulation of the PRL mRNA, as well as several other mRNAs, in the rat pituitary tumor GH3 cell line. Serum-deprived cells progressed from G0 to S phase in 20-24 h following serum stimulation. During this time, beta-actin mRNA levels increased 7-fold in 5 h, then returned to basal levels prior to the beginning of S phase. Histone H1 mRNA levels increased approximately 3-fold as cells entered S phase. These data are consistent with the cell cycle-dependent regulation of beta-actin and histone H1 gene expression reported for other cell types. Glucocorticoid receptor mRNA levels were barely detectable in serum deprived cells but rapidly increased 3- to 5-fold following serum stimulation. This increase resulted in glucocorticoid receptor mRNA levels that were equivalent to those seen in cells maintained in serum-containing medium, suggesting that serum factors regulate glucocorticoid receptor gene expression. In contrast to these changes in gene expression, the levels of PRL and growth hormone (GH) mRNAs gradually increased 2-fold while the cells progressed through G1 phase. Similarly, in cells synchronized to progress through S and G2 phases following aphidicolin treatment, histone H1 gene expression showed a specific increase in S phase cells, whereas PRL and GH mRNA levels changed little with cell cycle progression. These results indicate that the levels of PRL and GH mRNAs are not regulated in a cell cycle-dependent manner. When changes in estrogen responsiveness were determined during the cell cycle, we found that estradiol treatment was capable of increasing PRL mRNA accumulation independent of cell cycle progression and cell cycle distribution in synchronized GH3 cells. These results support the hypothesis that the hormonal regulation of PRL gene expression is not significantly affected by cell growth. PMID- 1761164 TI - Potentiation of thyrotropin-releasing hormone-stimulated prolactin mRNA levels in GH3 cells by acetylcholine. AB - We have examined the effect of acetylcholine (ACh) pretreatment on the thyrotropin-releasing hormone (TRH) induced prolactin gene expression in GH3 cells, a rat pituitary tumor cell line. Prolonged exposure (greater than 6 h) to ACh enhanced the TRH-induced prolactin mRNA accumulation in a time- and concentration-dependent manner while ACh by itself did not affect the basal prolactin mRNA levels appreciably. Maximal augmentation of the TRH-induced prolactin mRNA accumulation was obtained when cells were pretreated with 10(-5) M ACh for 24 h. The activation was mimicked by carbachol and oxotremorine and was blocked by the simultaneous presence of atropine. Preincubation of GH3 cells with pertussis toxin abolished the augmenting effect of ACh. These results indicate that prolonged exposure to muscarinic receptor agonists may enhance the TRH stimulated prolactin mRNA expression and a pertussis toxin sensitive G-protein may be involved. PMID- 1761165 TI - Crotoxin, a phospholipase A2 neurotoxin from snake venom, interacts with epithelial mammary cells, is internalized and induces secretion. AB - Prolactin (PRL) induces liberation of arachidonic acid (AA) from phospholipids of lactating mammary epithelial cells and stimulates casein secretion. In order to investigate the possible involvement of phospholipase A2 (PLA2) activity in the hormonal control of casein secretion by PRL, we examined the effects of crotoxin, a PLA2 neurotoxin from snake venom, on mammary epithelial cells. Crotoxin is made of two subunits: a basic PLA2 with low toxicity (component B, CB) and an acidic, non-toxic and enzymatically inactive component A (CA) which enhances the pharmacological action of CB. While CA is inactive, the PLA2 subunit (CB) induces an accumulation of secretory products in the lumen of mammary acini, an extensive development of the Golgi apparatus. The secretion of newly synthesized casein is increased in the presence of CB and this effect is inhibited by nordihydroguaiaretic acid (NDGA) and caffeic acid, two inhibitors of the lipoxygenase pathway which also prevent stimulation of secretion by PRL. Further, CB transiently induces the release of radiolabelled AA from mammary tissues previously labelled with [14C]AA, the highest release being observed between 15 s and 5 min of contact with CB and CA. Immunofluorescence labelling by anti-CB antibodies of epithelial mammary tissues previously incubated with CA, CB or a combination of CA and CB indicates that CB binds to epithelial cells and is internalized, at least in part, and that CA enhances both CB binding and its internalization. These observations emphasize the involvement of PLA2 in the control of casein secretion and suggest that PLA2 acts intracellularly. PMID- 1761166 TI - Processing of pro-CGRP in a rat medullary thyroid carcinoma cell line transfected with protease inhibitors. AB - A rat medullary thyroid carcinoma cell line, CA77, was used to study the effect of a series of biosynthesized protease inhibitors on the proteolytic cleavage of the endogenously synthesized pro-CGRP. This cell line efficiently converted the pro-CGRP to mature CGRP as assessed by chromatography of cell extracts followed by radioimmunoassay for CGRP. CA77 cells were transfected with expression vectors encoding protease inhibitors: the Arg-serpins, alpha 1-antitrypsin Pittsburgh (358 Met----Arg) and plasminogen activator inhibitor 1, the Kazal type serine protease inhibitor, pancreatic secretory trypsin inhibitor, and the general thiol protease inhibitor, cystatin C. Only the chromatography of cell extracts from CA77 cells transfected with a plasmid encoding cystatin C showed an apparent higher content of unprocessed pro-CGRP as compared to non-transfected cells. No effect on pro-CGRP processing could be measured in the CA77 cells transfected with plasmids encoding the three serine protease inhibitors. CA77 cells were also transfected with two constructs encoding chimeric proteins consisting of cystatin C and the precursor for neuropeptide Y. Release experiments using 8-bromo cAMP as the secretagogue showed that the chimer was co-released with CGRP. However, no effect of this chimer upon pro-CGRP processing could be detected. It is concluded that the processing of pro-CGRP in the CA77 cell line was very efficient and that four different protease inhibitors and two cystatin C/NPY chimers synthesized by this neuroendocrine cell line had only minimal effect upon the processing of CGRP. PMID- 1761167 TI - [Therapy of endometrial cancer]. AB - Surgical-pathological categorising of endometrial carcinoma makes it possible to treat this cancer in a more differentiated way. In clinical stage I, 6% of the adnexes, 10% of the pelvic lymph nodes and 5% of the paraaortic lymph nodes are affected. There is a direct correlation between depth of invasion and pelvic and paraaortic lymph node metastases. The new surgical-pathological categorising of endometrial carcinoma requires extensive surgery. Lymphadenectomy, which is necessary for categorisation means over-treatment for 2 thirds of all cases. Today, low-risk endometrial cancers can be distinguished from high risk ones by vaginal sonography as well as NMR permits the detection of invasion preoperatively and curettage to determine the unfavorable subtypes (seropapillary, clear-cell), hormonal receptors and ploidy. In low-risk cases, hysterectomy (with adnexes) and careful revision of the abdomen is sufficient. No further adjuvant therapy is necessary. In high-risk cases, an extended pelvic and, in the case of metastases, an para-aortic lymphadenectomy is imperative. Percutaneous X-ray therapy is not necessary in low-risk cases postoperatively. In high-risk cases, its effectiveness is not established and is probably not superior to the operative removal of metastases. Radiation of the vaginal cuff is necessary and successful in high-risk cases. In low-risk cases, side-effects are minimal. Adjuvant therapy with gestagens in low-risk cases is not indicated, because of their side-effects and does not reduce recurrence rate. Recurrent and metastasizing endometrial carcinomas respond to gestagens in about 15% of cases. Response is receptor dependent. High dose is not more effective. Endometrial carcinoma responds to chemotherapy. Most effective is adriamycin with a response rate of 35%. Combination therapies did not show greater effect in randomized studies. Recurrence free interval is only 6 to 8 months, however. An adjuvant chemotherapy is only indicated in the case of a serous carcinoma. PMID- 1761168 TI - [A risk score for operated endometrial cancer and its importance for adjuvant radiotherapy (histopathology and results of treatment based on 208 cases with pelvic lymph node excision)]. AB - In a retrospective study of 208 surgically treated cases of endometrial cancer with pelvic lymphadenectomy, histomorphology with subtypes, tumour grading, infiltration of the myometrium, blood- and lymphatic vessel invasion and pelvic lymph node metastases, were analysed. Typical adenocarcinomas had lymph node involvement in 9% of the patients, whereas unfavourable subtypes showed in 27%. In patients with tumour grading I, the lymph nodes were involved in only 4.5% and with grading 3 in 31.4%, respectively. If the carcinoma was limited to the endometrium, no lymph node metastases could be detected. If the inner half of the myometrium was involved, pelvic nodes were positive in 9.2% with deeper infiltration in 27.3% of the cases. With obvious invasion of blood or lymph vessels, lymph nodes were positive in 43.2% of the cases. A simple score for these histopathological risk factors is proposed, enabling the allocation to patient groups of similar risk on the basis of a point system for individual prognostic factors. With a score of 1-2 points (13.5% of the cases) the prognosis is good and adjuvant irradiation does not seem necessary. With 3-4 points (34.1% of the cases), local vaginal irradiation is recommended. With 5 or more points, we recommended, in addition to vaginal irradiation, aggressive irradiation of the small pelvis, 52.4% were in this group, from which 85% were symptom-free at the critical 5 year point. In case of positive pelvic lymph node, 67% of the patients survived after adequate adjuvant follow-up irradiation. PMID- 1761169 TI - [Prognostic factors in stage Ia-IIb invasive cervix cancer after radical hysterectomy with special reference to stroma reaction]. AB - 158 cases of invasive carcinoma of the uterine cervix stages Ia to IIb were analysed with respect to the following prognostic criteria: histological stage, presence of nodal metastases, vascular space invasion and inflammatory stromal reaction at the periphery of the tumor. The assessment of these criteria was correlated to the prevalence of tumor recurrence. In cases with absent nodal metastases, a significant increase of tumor recurrence in stage IIb compared to other stages was noted. A constant increase of the recurrence rate was found, when nodal metastases were present, although the incidence of positive lymph nodes was approximately equal in stages Ic, IIa and IIb. The involvement of the parametrium therefore appears to be a significant parameter for the poor prognosis in stage IIb. Vascular space invasion proved to be a significant parameter with regard to lymph node involvement. When no vascular space invasion was obvious, 94% of the cases showed tumor-free lymph nodes. Overall, heavy inflammatory infiltration at the tumor periphery correlated with a good prognosis. In cases of heavy inflammatory stromal reaction, the risk of nodal metastases and tumor recurrence was significantly lower, independent of the histological stage. The incidence of heavy inflammatory infiltration was significantly higher in microinvasive carcinomas than in clinically invasive tumors. Therefore, the extent of inflammation appears to be an additional useful prognostic index to identify a group of patients at high risk for recurrence and reduced chance of survival. PMID- 1761170 TI - [Posterior exenteration with plastic reconstruction in advanced vulvar cancer]. AB - Between 1984 and 1990, twenty-four patients suffering from advanced primary (7) or recurrent (17) valvular carcinoma were treated by posterior exenteration and myocutaneous reconstruction of the defect. During a follow-up of 34 months, the overall survival was 49%. Eight patients died. Tumour diameter and tumour-free margins of the resected specimens were the most important prognostic factors. In all cases, an improved quality of life could be achieved by the operation. It is concluded that, even in extremely difficult situations, posterior exenteration, followed by plastic reconstruction entails an essential benefit for the patient. PMID- 1761171 TI - [Reactions to stress during the normal menstrual cycle]. AB - In the present study, we questioned, whether the variability of physiological parameters within a menstrual cycle are connected with psychological variables like mood, state of health and positive/negative daily occurrences. We examined 20 women with normal cycles. The definition of a normal cycle was: 28 (+/- 5) days of length, standard weight according to Broca, 3-5 days menstrual bleeding, no oral contraceptive during the last 6 months, no IUP, inconspicuous hormones (no raised prolactin or testosterone levels), gynecologically unremarkable findings. Gynecological and psychological data were gathered daily during one menstrual cycle: hormone levels, vaginal ultrasound for detecting follicle growth, ovulation, corpus luteum and endometrial development. The psychological data on mood, state of health and positive/negative occurrences were recorded in parallel in the form of a diary, in which new entries were made daily. The results showed, that only 6 out of the 20 women had a normal menstrual cycle as defined above. Women with a normal (physiological) cycle, report in their diary: less negative bodily tendencies, more positive everyday situations, but the same amount of negative situations as women with noticeable cycles. Both the normal cycle group and the conspicuous cycle group report more negative body states and more negative moods in the premenstruum than the middle phase. The implications of these results are discussed. PMID- 1761172 TI - [Endoscopic bladder neck suspension--clinical, urodynamic and radiologic results]. AB - 70 women were evaluated clinically and urodynamically both before and, on average 16 (12-48) months after undergoing endoscopic suspension of the bladder neck, following Stamey, for genuine stress urinary incontinence. The average age of the patients at surgery was 52 (35-85) years; the average parity was 3 (0-10). Preoperative and postoperative lateral colpocystograms were performed on 48 patients. 40 patients had marked descent of the pelvic organs; 30 patients had previously undergone vaginal hysterectomy and anterior colporrhaphia. Overall, 70% of the patients were postoperatively clinically and urodynamically continent at follow-up; however, only 44% of the patients with a preoperative urethra closure pressure (UCP) less than 20 cm H2O were continent. The functional urethral length was unchanged but the point of maximum closure pressure was shifted to the proximal third of the urethra. The UCP at rest decreased significantly (p = 0.0277). Radiologically, the bladder neck was elevated further and the angle beta decreased more in the patients continent after surgery, than in those who remained incontinent. These data suggest that the Stamey operation is effective in selected patients with stress incontinence, but not in patients with a low UCP at rest. PMID- 1761173 TI - [The effectiveness of intravaginal estriol tablet administration in women with urge incontinence]. AB - In postmenopausal patients, stress and urge incontinence often occur as a consequence of oestrogen deficiency. We performed a comparative study in a prospectively randomised and placebo controlled group of women with urge incontinence to investigate different dosages of intravaginally applied oestriol. Clinical and urodynamic parameters were also compared. 15 women (Group I) received 1 mg oestriol applied daily intravaginally over 3 weeks; 15 women (Group II) received a daily dosage of 3 mg and 10 women received a placebo. A complete clinical and urodynamic evaluation was carried out twice at a 4-week interval. The women receiving a daily dose of 3 mg oestriol applied intravaginally demonstrated a significant improvement of the parameters strong desire to void, pollakisuria, and nycturia. No improvement was seen in patients with motoric urge incontinence. PMID- 1761174 TI - [Local administration of metronidazole before hysterectomy--effect on infectious morbidity. A prospective study]. AB - A prospective clinical trial was designed to examine the influence of a local application of metronidazole on postoperative infectious morbidity in 134 women undergoing vaginal and in 108 women undergoing abdominal hysterectomy. 116 patients received on the evening before hysterectomy a vaginal suppository of metronidazole (500 mg). The control group (126 patients) had no metronidazole prophylaxis. All patients, who underwent vaginal hysterectomy, were given additionally a single-shot prophylaxis with 1500 mg cefuroxim. With regard to febrile morbidity, urinary tract infection and abdominal wound or pelvic infection, there was a significant decrease in infectious morbidity. In women undergoing vaginal hysterectomy the infectious morbidity was reduced from 35.7% to 20.3% (p less than 0.05) in spite of systemic prophylaxis. In cases with abdominal hysterectomy, we saw a decrease from 64.3% to 26.9% (p less than 0.001). There was no effect on the incidence of urinary tract infections. Local prophylaxis with metronidazole in abdominal hysterectomy and additional to a systemic prophylaxis in vaginal hysterectomy reduces the infectious morbidity in our patients. PMID- 1761175 TI - [Trends in surgery of gynecologic cancers]. PMID- 1761176 TI - [Modification of the use of a magnetic device for urethral occlusion in recurrent incontinence]. AB - The magnetic closure device consists of a bow-shaped retropubically implanted magnet. Another removable magnet is situated in the vagina, thus gently closing the urethra. The modification described herein consists of colposuspension over the upper edge of the implanted magnet. Continence was thus achieved. The use of the intravaginal magnet was not necessary. The case report deals with the first two patients. PMID- 1761177 TI - [Reduction-plasty of the breast in symmastia]. AB - Medial confluence of the breasts, known as symmastia, has received little attention in plastic surgery literature. By reporting on one case, we present our surgical technique. The chosen method of the reduction mammoplasty is considered to be particularly important. Liposuction is integrated into the surgical procedure. Suggestions made by other authors are discussed. PMID- 1761178 TI - [Recurrent multicystic peritoneal mesothelioma in endometriosis of the pelvis]. AB - In the case of a 21-year old woman, who complained of chronic pelvic pain and where cystic structures in the adnexal region had been diagnosed ultrasonically and by laparoscopy, a tumour made up of many small cysts was discovered in the pouch of Douglas next to a typical endometrial cyst. Both the endometrial cyst and the cystic tumour were excised by laparotomy. Histology established the tumour as a multicystic peritoneal mesothelioma. Postoperative recurrence was noticed by ultrasound less than one year later. Laparotomy revealed a 5 cm serous cyst of the right ovary and again countless liquid-filled grape-like small cysts in the pouch of Douglas. Histology revealed a multicystic peritoneal mesothelioma identical to the previously excised tumour. Multicystic peritoneal mesothelioma is a rare soft tissue tumour noted for its frequent recurrences. Most authors agree, that it belongs to the morphological spectrum of reactive mesothelial proliferative lesions and not the neoplastic spectrum. It appears mostly in women, often concomitant with endometriosis and pelvic inflammatory disease and frequently in women, who had previous surgical interventions in the abdominal region. PMID- 1761179 TI - [Prenatal diagnosis of malignant intracranial teratoma in the fetus]. AB - At 24 weeks of gestation, an intracranial cystic lesion of 3 cm diameter, without further associated foetal malformations, was detected by ultrasound in a 25-year old nullipara prima gravida, during routine prenatal care. Within 5 weeks, the cystic mass developed into a predominantly solid tumour located at the 3rd ventricle, showing patterns of a rapidly growing malignant intracerebral process. At 29 weeks of gestation, pregnancy was terminated by sectio parva because of a progressive hydrocephalus with a biparietal diameter of 10.2 cm. Autopsy confirmed a malignant teratoma. Foetal intracranial teratomas are rare. Diagnosis and therapy should be carried out in perinatal centres. PMID- 1761180 TI - Effect of repeated administrations upon cathinone discrimination and conditioned place preference. AB - 1. Eight male rats were trained to discriminate the interoceptive cues produced by 0.8 mg/kg l-cathinone in a two-lever, food-motivated operant task and they were, subsequently, tested for preference to cathinone in a conditioned place preference (CPP)-test. 2. Once trained, the rats were placed on a 10 day regimen of twice-a-day non-contingent administrations of saline followed by a similar regimen of multiple injections of 0.8 mg/kg cathinone. 3. After each series of non-contingent administrations, the rats' ability to discriminate (0.2-0.8 mg/kg) cathinone, as well as their preference for it, was determined. 4. Results indicate that tolerance tends to develop to the effect of cathinone in its ability to control discriminative behavior as indicated by deficits in discriminative performance and a two-fold shift of the dose-response curve to the right. 5. In contrast, preference for cathinone, in the CPP-tests, was not significantly affected by the multiple cathinone administration regimen. 6. The possibility that tolerance to some behavioral effects may occur in habitual users of the cathinone-containing Khat shrub is discussed. PMID- 1761181 TI - Effect of ageing on response to nicotine in rabbit bronchial preparation. AB - 1. Effect of ageing on the response to nicotine was tested in the bronchial muscle preparations from 5, 13, 100 and 125 week-old rabbits. The pD2 value (potency) of nicotine significantly increased in the preparation from the 125 week-old rabbits. No age-related change was found in the pD2 value of carbamylcholine or pA2 value of atropine. 2. No age-related change in characteristics of nicotine receptors. Choline acetyltransferase activity, the amount of acetylcholine released by nicotine and acetylcholineesterase activity decreased in the preparations from the 125 week-old rabbits. 3. Decrease in the pD2 value of nicotine in the preparation from the older rabbit is due to a decline in choline acetyltransferase activity followed by a reduction in the acetylcholine released, and not to a change in characteristics of nicotine receptors. 4. These results also suggest that enzymes may be influenced more easily with age than drug receptors. PMID- 1761182 TI - Ampicillin concentrations in human oral tissues following a single oral administration of lenampicillin. AB - 1. Ampicillin concentrations in serum (n = 20), gingiva (n = 12), jawbone (n = 13), dental follicle (n = 12), radicular granuloma (n = 2) and radicular cyst (n = 2) were measured in specimens obtained during 0.5-2.5 hr after a single oral administration of lenampicillin (equivalent to 500 mg of ampicillin). 2. Measurable ampicillin concentrations were found in all serum and tissues. 3. Ampicillin concentrations in serum and tissues except for some gingiva and jawbone exceeded MIC for 90% of clinically isolated strains of alpha-hemolytic Streptococci. 4. Ampicillin concentrations in gingiva and jawbone were below the MIC for 90% in 2 out of 12 and 4 out of 13 specimens, respectively. PMID- 1761183 TI - Effect of bradykinin antagonists, NG-monomethyl-L-arginine and L-NG-nitro arginine on phospholipase A2 induced oedema in rat paw. AB - 1. The rat paw oedema produced by a local injection of phospholipase A2 from Naja mocambique mocambique has been shown to be mainly driven by the liberation of serotonin and kinins. 2. Using specific bradykinin receptor antagonists we have shown that kinins are acting through B2 receptors. 3. Using endothelium-derived relaxing factor (EDRF) synthesis inhibitors NG-monomethyl-L-arginine and L-NG nitro arginine we have tested the possible envolvement of EDRF as mediator. 4. Our work supports the view that extracellular phospholipases A2 are involved in inflammation, and suggests a role for EDRF as mediator of extravasation in this model of inflammation. PMID- 1761184 TI - Evaluation of synergism of drugs cis-diamminedichloroplatinum (II) and arabinosylcytosine on the level of chemical interaction with DNA and on the growth of mouse leukemia. AB - 1. Cytotoxic synergism of drugs cis-diamminedichloroplatinum(II) (cis-DDP) and arabinosylcytosine (araC) was studied both on the level of interaction with DNA in chemically determined conditions and on leukemia L1210 bearing mice. 2. AraC and its structural natural precursor cytidine were tested for the modulation of kinetics of bifunctional adducts production induced by cis-DDP in DNA. 3. This process plays the basic role in cytotoxic mechanism and antitumor activity of cis DDP. 4. No interaction was seen between cis-DDP and araC. Further, presence of araC in reaction mixture had no effect on cis-DDP-DNA interaction. 5. Therefore, cytotoxic synergism does not arise in the araC-cis-DDP-DNA interaction and its origin is different. 6. Finding that cytidine has no synergistic effect on life span of leukemia L1210 bearing mice when administered together with cis-DDP it shows the difference between cytidine and araC. 7. The small structural difference between cytidine and araC is very important for synergism of cytotoxicity. PMID- 1761185 TI - Operant food intake in pigs following intracerebroventricular (i.c.v.) administration of prolactin. AB - 1. It has previously been shown that systemic administration of prolactin stimulates food intake in a number of animal species. 2. In the present study we investigated whether central administration of prolactin would increase food intake in satiated pigs trained to make operant responses for food and water. 3. Prolactin (25-100 U) administered by intracerebroventricular (i.c.v.) injection produced no significant effects on food intake during the 60 min measurement period after injection. 4. Furthermore, none of these doses of prolactin had any effect on the daily (24 hr) consumption of food in these animals. 5. Similarly prolactin (25-100 U) i.c.v. had no significant short or long-term effects on water intake. 6. These results indicate that prolactin does not stimulate food intake in pigs by a central mode of action. PMID- 1761186 TI - Lasting impact of a single benzpyrene treatment in pre-natal and growing age on the thymic glucocorticoid receptors of rats. AB - 1. Rats exposed to benzpyrene in utero at 19 days of pre-natal life showed a relative decrease in the number of thymic glucocorticoid receptors at 6 weeks of age. 2. Primary exposure to benzpyrene at 6 weeks of age had a similar effect on females 4 weeks later, but did not change the glucocorticoid receptor number of males. 3. In utero exposure accounted for an increase in the fetal cytochrome P450 level within 1 day, whereas exposure at 6 weeks of age did not change it within 4 weeks. 4. It appears that exposure to benzpyrene gives rise to a faulty imprinting of the thymic glucocorticoid receptor in both fetal and growing age, to judge from a lasting change in the receptor number. PMID- 1761187 TI - Participation of opioid peptide (beta-endorphin) and norepinephrine in the control of compound 48/80-induced hypovolemic thirst in the rats. AB - 1. Subcutaneous (s.c.) administration of compound 48/80 elicited the increases of water intake, plasma beta-endorphin-like immunoreactivity, hypothalamic 3-methoxy 4-hydroxyphenylethyleneglycol sulfate and Hct in the rats. 2. The s.c. pretreatment of naloxone reduced the compound 48/80-induced water intake but had no effects on other variables. 3. Intracerebroventricular (i.c.v.) injection of naloxone attenuated the compound 48/80- and i.c.v. injected angiotensin II (ANG II)-induced water intake. 4. The hypothalamic norepinephrine metabolism was increased by s.c. injection of compound 48/80 but not by i.c.v. ANG II. 5. The present data suggest the possible involvement of opioid peptide (beta-endorphin) on the compound 48/80- and ANG II-induced thirst. However, it is uncertain whether hypothalamic norepinephrine is involved in the hypovolemic thirst mediated via stimulation of renin-angiotensin system. PMID- 1761188 TI - Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues. AB - 1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs. PMID- 1761189 TI - Trichosanthin induces atresia of ovarian follicles and inhibits steroidogenesis in gonadotropin-primed immature mice. AB - 1. Immature mice were induced to ovulate by injections of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin spaced 48 hr apart. 2. Trichosanthin (TCS), a protein purified from tubers of Trichosanthes kirilowii (Family Cucurbitaceae), was administered respectively 24 hr before, on the same day as, 24 hr after and 48 hr after the PMSG injection. 3. The results of TCS injections at different times were generally similar. The number of maturing follicles, corpora lutea and ovulated oocytes, and the ovarian weight, remained unaltered. 4. However, there was an increased incidence of follicular atresia and degeneration of ovulated oocytes, and a lowering of serum estradiol-17 beta and progesterone levels. PMID- 1761190 TI - Characterization of muscarine receptors in rabbit ciliary body smooth muscle using propylbenzilylcholine mustard. AB - 1. A piece of rabbit ciliary body was mounted in organ bath and used as a test organ containing muscarine receptors. 2. A concentration response curve of carbachol was completely inhibited by a 50 min treatment of the smooth muscle preparation with propylbenzilylcholine mustard(PrBCM; 10(-6) M). This treatment was reported to block PrBCM-sensitive muscarine receptors in intestinal smooth muscle completely. 3. It is suggested that an existance of only PrBCM-sensitive muscarinic receptors, though there are two subtypes of muscarine receptors; PrBCM sensitive and -resistant ones in intestinal smooth muscles. PMID- 1761191 TI - Inhibition of prostaglandin synthetase alters uterine response to adrenoceptor agonists in pregnant and post-partum rats. AB - 1. The involvement of intramurally generated prostaglandins in uterine response to adrenoceptor agonists has been investigated in rats during late pregnancy and post partum. 2. Both adrenaline and salbutamol (10(-9)-3 x 10(-7) M) produced concentration-dependent inhibition of acetylcholine-induced tone in preparations from 20-day pregnant and 1-day post-partum rats. 3. Inhibition of prostaglandin synthetase with flurbiprofen enhanced uterine response to these agonists in late pregnancy and post partum. 4. In endometrium-free preparations, flurbiprofen treatment had no significant effect on myometrial responses to adrenaline and salbutamol, suggesting a role for the endometrium in the interaction between adrenoceptor agonists and the prostaglandin synthetase pathway. 5. The above results provide pharmacological evidence for the involvement of prostaglandins in rat uterine response to adrenoceptor agonists during pregnancy and post partum. PMID- 1761192 TI - Effect of RU-38486 on dexamethasone reversal of morphine-induced constipation in mice. AB - 1. Morphine and dexamethasone significantly reduce gastrointestinal transit in mice. The degree of reduction was greater for morphine. 2. Dexamethasone pretreatment was found, however, to antagonize morphine-induced constipation. 3. Cycloheximide does not modify the dexamethasone effects. 4. RU-38486 reverses both the inhibitory action of dexamethasone on gastrointestinal transit and its reducing effect on morphine-induced constipation. 5. These results suggest that dexamethasone might act through binding to receptors not linked to DNA-responsive elements. PMID- 1761193 TI - Purinergic modulation of field stimulation responses of rat and human vas deferens smooth muscle. AB - 1. Guanethidine at 5 x 10(-6) M strongly inhibited rat prostatic but not epididymal vas deferens, reflecting differences in innervation and the neurogenic field stimulation responses of these tissues. 2. Adenosine and ATP inhibited the field stimulation responses of rat prostatic vas deferens by 56 and 50% respectively. A 10-min pretreatment with 10(-4) M caffeine partly reversed this inhibition, by 55% in the case of adenosine and 60% for ATP. 3. Pretreatment for 10 min with 5 microM quinidine failed to significantly alter the extent of either adenosine or ATP inhibition of the field stimulation responses of rat prostatic vas deferens. 4. 8-Phenyltheophylline, the selective blocker of the A1 subtype of the P1 receptor, partly reversed adenosine-induced inhibition of the vas deferens FS responses. NECA, the selective agonist of the A2 subtype of the P1 receptor, very strongly inhibited vas deferens FS responses. 5. Field stimulation responses of human vas deferens were also inhibited by both adenosine and ATP but to a lesser extent and more variably than in rat tissue. 6. Adenosine and ATP inhibition was reversed by caffeine pretreatment, but far more variably than in rat tissue, and quinidine was without significant effect on inhibition of the responses. 7. It is concluded that in these tissues adenosine and ATP may operate via a P1 type receptor of both A1 and A2 subtypes and that a P2 type receptor may be lacking. PMID- 1761194 TI - Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines. AB - 1. The changes in the levels of brain biogenic monoamines (BMAs) after chronic (7 days) treatment with piracetam, aniracetam and structural analogues of aniracetam (p-H, p-F, p-Cl, p-P and m-D) were studied in young and old rats. 2. An age related significant decrease in the BMA content was established in old rats. 3. Most of the investigated compounds increased the level of one or other BMA in one or other of the brain structures studied. This elevation was predominantly established in old rats. 4. The present results and those from previous behaviour studies show that elevation of one or more of the BMA levels in one or more brain regions plays a beneficial role in the realization of their effects on the processes of learning and memory. PMID- 1761195 TI - Comparative effects of adrenaline and noradrenaline on the synthesis and secretion of soluble protein by isolated hepatocytes. AB - 1. Adrenaline (A) supplementation of the incubation medium of monolayer cultures of hepatocytes at 0.1, 0.2, 0.3, 1 and 10 ng/ml resulted in consistently enhanced levels of secreted and newly synthesised non-secreted proteins; supplementation with 100 and 1000 ng/ml resulted in lower or unchanged levels. These effects were most consistent 6 hr after a medium change. 2. Noradrenaline supplementation of the medium resulted in increased levels of secreted and non-secreted proteins at low concentrations (less than 2.4 ng/ml) at 6 hr after a medium change, but significantly decreased levels of both populations at high concentrations of noradrenaline (NA) (2.4 less than NA less than 1000 ng/ml), at 6-9 hr after a medium change and sustained to 24 hr, the most significant decrease being at 10 ng/ml. 3. All combinations of concentrations of A + NA resulted in non-dose dependent decreased levels of both the secreted and non-secreted soluble protein fractions. The most significant decreases occurred at concentrations of (1 + 5) and (10 + 10) ng/ml adrenaline + noradrenaline. 4. Medium supplementation with adrenaline, noradrenaline or a combination of the two had no effect on the uptake of [3H]leucine by the cells. 5. The results are discussed in relation to receptor status on the hepatocyte membranes. PMID- 1761196 TI - The effect of cyanide on vitamin C uptake by human polymorphonuclear leukocytes. AB - 1. Cyanide inhibited the uptake of vitamin C by human polymorphonuclear leukocytes (PMNs). 2. Preincubation of PMNs with cyanide had no effect on cytochalasin B-inhibitable uptake of dehydroascorbic acid (DHA) (the reversibly oxidized and transportable form of vitamin C). 3. Preincubation of DHA with cyanide resulted in inhibition of DHA uptake. 4. Vitamin C uptake was decreased by cyanide to the same degree as it was by glutathione (GSH), which effectively reduces DHA to ascorbic acid. The effects of cyanide and GSH were not additive. 5. The data are consistent with the hypothesis that cyanide inhibition of vitamin C uptake represents the chemical elimination of extracellular DHA rather than the inhibition of active transport in these cells. PMID- 1761197 TI - The interaction of peripherally and centrally administered dexamethasone and RU 38486 on morphine analgesia in mice. AB - 1. Dexamethasone or RU 38486 were administered intraperitoneally or intracerebroventricularly to mice 10 or 120 min before morphine administration. The interaction of these drugs with the analgesic effects of morphine was examined using the hot plate test. 2. Dexamethasone i.p. pretreatment reduced analgesic responses to morphine injected 120 min but not 10 min after dexamethasone; i.c.v. injection of dexamethasone 10 and 120 min before morphine administration was effective in reducing morphine analgesia. 3. RU 38486 i.c.v. pretreatment (but not i.p. pretreatment) performed 120 (but not 10) min before morphine administration enhanced morphine analgesic effects. 4. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for dexamethasone and RU 38486 action. PMID- 1761198 TI - The effect of verapamil on the thermoregulatory responses produced by endotoxin or noradrenaline in rabbits. AB - 1. Thermal responses to verapamil (5 mg/kg per hr) were investigated in pyrogen (lipopolysaccharide Escherichia coli) or noradrenaline (NA) treated rabbits. 2. The compound reduced the pyretic, metabolic and vasoconstricting activity of pyrogen. 3. On the other hand, verapamil did not significantly affect NA-induced hyperthermia. 4. Possible mechanisms responsible for the thermoregulatory activity of verapamil are discussed. PMID- 1761199 TI - The effects of chronic administration of morphine on the levels of brain and adrenal catecholamines and neuropeptide Y in rats. AB - 1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with morphine. 2. The well-recognized biochemical alterations (serotoninergic turnover increased in the hypothalamus, hippocampus and striatum; dopaminergic turnover increased in the striatum and cortex; adrenaline levels decreased in the adrenal glands) were observed. 3. In addition, we observed a significant decrease of the NPY levels in the hypothalamus, the striatum and the adrenal glands. The observed changes were not reflected in plasma. 4. Our results contribute to the evidence that brain and adrenal monoamines and NPY could be involved in the mechanism of morphine tolerance and/or dependence. PMID- 1761200 TI - Respiratory and circulatory effects of centrally administered phencyclidine in anesthetized dogs. AB - 1. Anesthetized dogs were given phencyclidine HCl (PCP) by intracerebroventricular (i.c.v.) injection. 2. Physiological parameters were monitored after consecutive doses of 0.5, 1.0 and 2.0 mg of PCP. 3. Dose-related changes seen, including bradycardia, hypotension and bradypnea, were opposite to those produced by i.v. doses. 4. Single doses of 1.0 or 2.0 mg of PCP confirmed the prior observations, and the latter provided the baseline for further observations on dogs receiving PCP before various i.c.v. pretreatments--atropine, haloperidol, phentolamine or propranolol--in efforts to characterize the central neurotransmitter system(s) involved in the PCP effects. PMID- 1761201 TI - Lipid peroxidation, glutathione and ascorbic acid concentrations in tissues of mice treated with oltipraz: influence of cysteine and olive oil pretreatments. AB - 1. The effects of treatment with the antischistosomal drug oltipraz on reduced glutathione (GSH), lipid peroxide (LP) and ascorbic acid (AA) concentrations in the liver, kidney and brain were studied in mice 24 h after drug administration. 2. The influence of pretreatment with cysteine or olive oil on the above variables in oltipraz-treated mice was also investigated. 3. Oltipraz, at single oral doses of 25 and 125 mg/kg, did not affect significantly the concentrations of GSH, LP or AA in any of the tissues studied. 4. At a dose of 625 mg/kg, the drug produced significant increases in GSH concentration in the liver (about 34%), kidney (38%) and brain (24%). 5. AA concentrations were not significantly affected by the drug treatment in any of the organs studied. 6. However lipid peroxide formation in the liver of mice treated with oltipraz (625 mg/kg) was less than that in control animals by about 45% (P less than 0.05). 7. In other organs it was not significantly affected by the treatment. 8. Oltipraz (625 mg/kg) was given orally to mice which were pretreated with cysteine (25, 50 and 100 mg/kg for 7 days intramuscularly). 9. The cysteine pretreatments did not affect significantly the increases in GSH caused by oltipraz alone, although they were effective in significantly increasing GSH concentrations in saline-treated mice. 10. The oltipraz-induced increases in the concentrations of GSH in liver and kidney was enhanced (by about 16%) by olive oil (0.2, 02 and 0.4 ml/mouse) when given 1 h before oltipraz treatment. 11. Concentrations of LP and AA were not significantly affected by olive oil pretreatment. PMID- 1761202 TI - Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia. AB - Low-density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = -13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with FCHL. PMID- 1761203 TI - Multivariate segregation analysis using the mixed model. AB - Most major genes involved in the etiology of complex diseases are likely to have pleiotropic effects on a number of intervening quantitative traits. Methods of segregation analysis that incorporate the additional information from such multiple traits will exhibit greater power for detecting the effects of major genes and allow explicit tests of major locus pleiotropy hypotheses. In this study, we present a new method for multivariate segregation analysis that utilizes a multivariate generalization of Hasstedt's [1982] technique for calculating approximate mixed model likelihoods on pedigrees. The method is based on a simplification of the multivariate conditional likelihood via a transformation that simultaneously orthogonalizes the residual additive genetic and environmental covariance matrices. This transformation allows the multivariate conditional likelihood to be factored into the product of independent univariate conditional likelihoods. Resulting computations are relatively fast, making it feasible to analyze multiple traits in extended pedigrees. We demonstrate our method with a bivariate analysis of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apo AI) serum levels in 585 pedigreed baboons. PMID- 1761204 TI - Affected kin-pair IBD methods: genetic models. AB - Cases of interest using affected sib-pair methods to distinguish between recessive and additive (dominant) modes of inheritance of a disease-predisposing gene involve goodness-of-fit tests with a small expected number in the "share zero parental haplotypes" category, as well as an unknown parameter, the frequency of the disease-predisposing allele. Our simulations demonstrate that the real significance level of the chi-square test using the three-haplotype sharing IBD values (share 2, 1, and 0 parental haplotypes) is close to the assumed (.05) level in these cases, so that the haplotype-sharing classes do not have to be lumped, which would leave no degrees of freedom for a statistical test. The validity of the chi-square approximation in cases of small expected frequencies has previously been described, but the situations that have been considered do not cover the very small values in the share-zero category that are often expected in the affected sib-pair analysis, nor do they involve estimation of an unknown parameter. Although including IBD values from affected kin pairs other than sibs can be a very powerful tool in demonstrating linkage of a marker and disease, these pairs do not add power, in fact they reduce the power, of the chi-square tests of goodness-of-fit of modes of inheritance. PMID- 1761205 TI - Estimating effects of probands' characteristics on familial risk: I. Adjustment for censoring and correlated ages at onset. AB - Family studies with age at onset of the disease as the endpoint face two important problems: censoring and correlation of age at onset among relatives. We present a multivariate survival model for ages at onset of relatives which incorporates the problems cited above. The interpretations of regression coefficients and association parameter in the context of family studies are emphasized. The present paper describes a statistical method for estimating these parameters. In a companion paper [Pulver and Liang, Genet Epidemiol 8:339-350, 1991] this model is applied to a genetic epidemiologic study of schizophrenia. PMID- 1761206 TI - Estimating effects of proband characteristics on familial risk: II. The association between age at onset and familial risk in the Maryland schizophrenia sample. AB - In this report we apply methods outlined in the companion paper [Liang, Genet Epidemiol 8:329-338, 1991] to study the association between proband age at onset and familial risk among first-degree relatives of 374 schizophrenic probands. The analyses take into consideration the potential problems of censoring and correlation of age at onset within families. All analyses were done by gender of the proband; age at onset was dichotomized. The results of the analyses of the male probands suggest that there is an increased risk of schizophrenia among the relatives of male probands who have an onset prior to age 17 when compared to relatives of male probands who have an onset later than 16. We did not find an association between age at onset and familial risk among the female probands, but this may be due to the smaller number of female probands and the lower power associated with the analyses. PMID- 1761207 TI - Genetics of total serum IgE levels: a regressive model approach to segregation analysis. AB - The genetics of basal total serum IgE levels was investigated in 278 individuals from 42 randomly ascertained nuclear families. The data were analyzed using the regressive model approach to segregation analysis with age, sex, and a measure of skin test responsiveness as covariates in the Class D models. The best fitting model was that of recessive inheritance of high IgE levels with a gene frequency of 0.99 for the "high" allele. Only 3 families showed evidence for segregation of the rare "low" allele, and, if extended further, these families could be useful for molecular genetic linkage studies. These results suggest that there may be a rare allele for very low total serum IgE levels that can be detected even after a measurement of allergic responsiveness (skin test results) is considered as a covariate. Therefore, this major gene for IgE levels appears independent of any similar locus controlling atopy. PMID- 1761208 TI - [Cloning of segments of the Drosophila melanogaster genome using artificial chromosomes of the yeast Saccharomyces cerevisiae]. AB - A partial genomic library from the Batumi L stock of Drosophila melanogaster was constructed using yeast artificial chromosomes as vectors. The DNA was restricted by Not1 and large fragments were inserted into the YAC5 vector. The size of cloned DNA varied from 90 to 500 kb. 48 random clones were characterized by in situ hybridization to the Batumi L polytene salivary gland chromosome. Single euchromatic sites of hybridization were detected for 27 clones; 11 clones revealed the main euchromatic hybridization site and several additional sites scattered along the chromosomes; 8 clones carried repeats which hybridized to chromocenter and other chromosomal sites; clones with 500 and 90 kb inserts originated from the Y chromosomes and nucleolus, respectively. The library is enriched by the repeated sequences related to the b-heterochromatin. PMID- 1761209 TI - [Genetic activity of aminofluorene and 2-acetylaminofluorene in strains of Saccharomycetes under conditions of in vitro metabolic activation: influence of rad 1-5 mutation]. AB - It has been shown that the rad1-5 mutation which alters excision repair in Saccharomyces cerevisiae yeast increased reversion frequency of the ochre mutation his7-1 and the frequency of intragenic mitotic recombination in the LYS2 gene induced by 2-aminofluorene and 2-acetylaminofluorene, as compared with the wild type strains activated in vitro by 39 mix from chicken liver. PMID- 1761210 TI - [Genetic instability of colonies' morphologic characteristics in the yeast Saccharomyces cerevisiae. The influence of mutations of radiosensitivity]. AB - The exposure to ionizing radiation of radiosensitive mutants of diploid yeast Saccharomyces cerevisiae deficient in double-strand break repair results in formation of morphologically unstable colonies. Some characteristics of this process were studied. The results obtained are consistent with the hypothesis on relationship between DNA double-strand breaks or their repair with the formation of unstable clones of diploid yeast cells. PMID- 1761211 TI - [Analysis of MGE Dm412 localization pattern in Drosophila melanogaster lines undergoing long-term selection for a quantitative character]. AB - The subpopulation composed of the mixture of Drosophila isogenic lines with interrupted wing radial vein (mutation radius incompletus, ri) was subjected to long-term selection in different directions for increase or decrease in expression of the ri gene. As a result, the lines with contrasting different values of mean character phenotype were developed. The isogenic lines of mean character phenotype were developed. The isogenic lines and F2 from their crosses with selected lines were analysed by the pattern of copia-like MGE DM412 localization. The isogenic lines were shown to have individual pattern, the selected lines differing strongly from them. Selection led to the loss of Dm412 localization sites during negative selection, while positive selection results both in loss and acquisition of sites. Correlation between the phenotype of the quantitative character and the pattern of MGE Dm412 was revealed. PMID- 1761212 TI - [A method of obtaining complementary "deletion-duplication" pairs on the posterior arm of Drosophila autosomes]. AB - A method for selecting pairs of deletion--tandem duplication in an autosome arm of Drosophila has been developed. Males containing autosome 2 and the right and left free arms of this autosome are producing gametes with metacentric and the free arm throughout meiotic nondisjunction. Unequal exchanges induced in such gametes give deletions and tandem duplications corresponding to the arm. This approach makes it possible to induce deletion without having a marker in the region under study. PMID- 1761213 TI - [Control of genetic consequences of vaccinations: electron microscopic analysis of murine synaptonemal complexes]. AB - The ability of two inactivated bacterial vaccines, from Proteus vulgaris and Klebsiella pneumoniae, to injure synaptonemal complexes (SCs) was studied by means of electron microscopy. The preparations were given intraperitoneally to C57BL/6J male mice during five successive days and testes were fixed 24 h after the last injection. Cyclophosphamide was used for positive control. The vaccine from Klebsiella given at subtoxic dose, which was about 200 times higher that that given to people during vaccinations, induced the 10-fold rise in the frequency of SC abnormalities in murine 1-storger spermatocytes. Breaks of SCs and of single lateral elements of SCs predominated over other types of vaccine induced anomalies. According to the preliminary data, vaccine from Proteus at subtoxic dose showed no damaging SC activity. The results of the given study are discussed in connection with the negative data obtained earlier when genotoxicity of these two vaccines had been studied in the Ames test, in routine investigations of bone marrow metaphases of vaccinated mice as well as under light microscopy of their SCs. PMID- 1761214 TI - [Verification of the color genotype based on morphological analysis of fur pigmentation of brown and black water voles Arvicola terrestris L]. AB - Qualitative and quantitative analysis of fur pigmentation in brown and black water voles (Arvicola terrestris L.) was performed. Morphology of pigment granules, their distribution along the hair layers and histology of hair bulbs were studied. Morphological data and the results of the analysis of segregation in the progeny, when brown voles were self-crossed and crossed with black ones, led to conclusion that fur colour of water voles is mediated by genes from the agouti series, precisely, black colour is determined by the extreme non-agouti allele (aeae genotype), and in brown voles which are homo- or heterozygous the colour is determined by the agouti allele (AA or Aae genotypes). PMID- 1761215 TI - [Chromosome differentiation of spiny rats of the genus Proechimys (Rodentia, Echimyidae)]. AB - Karyological analysis of spiny rats of the genus Proechimys revealed four chromosome forms: 2n = 30; 2n = 29; 2n = 28; 2n = 24. 30-chromosome spiny rats are characterized by unique karyotype constitution. 27-chromosome spiny rats from the territory near Iquitos differ from the same of Pucalpa (Ucayali Department) by Y-chromosome structure and banding of long arms with two pairs of autosomes. 24-chromosome rats from the regions mentioned above do not differ in G-banded chromosomes. Diploid chromosome set equal to 29, has a family originated from the parents which had 2n = 30 and 2n = 28 under the laboratory conditions. The absence of clear morphological differentiation, similarity of constituent parts of the karyotype and hybridization possibility point to relatively recent origination of the chromosome forms under study. PMID- 1761216 TI - [Component analysis of craniologic characters of silver foxes (Vulpes fulvus Desm.) and their changes arising under domestication]. AB - The data on cranial measurements performed in silver foxes indicate that there are differences in sizes measured between the farm foxes--bred population and the population selected for domestication. A method of principal components was used to analyse the cranial measurements and their changes under domestication. The first component covers about 50% of cranial diversity, which is interpreted as variation in the total skull size. This component clearly separates the two sexes, but not different populations. The second component presumably reflects the growth rate allometry between the skull length and width. The third and fourth components are measurements of skull width; the fifth one reflects the sizes of brain skull. None of these components clearly separate the foxes from farm--bred and domesticated populations. However, some differences in distribution are observed. PMID- 1761217 TI - [Genetics of Caucasian ethnic groups: distribution of some immunologic and biochemical markers in the Dagestan ASSR]. AB - Distribution of the genetic markers of blood groups (AB0, Rhesus, MN, MNSs, P, Kell-Cellano); plasma proteins (Hp, C'3, Tf, Gc); red-cell enzymes (AcP, EstD, GLO-1) and also ABH-secretion was studied among 6 ethnic groups of Dagesthan. Distribution of gene frequencies in Dagesthan populations and other Caucasian ethnic groups was comparatively studied. PMID- 1761218 TI - High-fidelity amplification using a thermostable DNA polymerase isolated from Pyrococcus furiosus. AB - A thermostable DNA polymerase which possesses an associated 3'-to-5' exonuclease (proofreading) activity has been isolated from the hyperthermophilic archaebacterium, Pyrococcus furiosus (Pfu). To test its fidelity, we have utilized a genetic assay that directly measures DNA polymerase fidelity in vitro during the polymerase chain reaction (PCR). Our results indicate that PCR performed with the DNA polymerase purified from P. furiosus yields amplification products containing less than 10% of the number of mutations obtained from similar amplifications performed with Taq DNA polymerase. The PCR fidelity assay is based on the amplification and cloning of lacI, lacO and lacZ alpha gene sequences (lacIOZ alpha) using either Pfu or Taq DNA polymerase. Certain mutations within the lacI gene inactivate the Lac repressor protein and permit the expression of beta Gal. When plated on a chromogenic substrate, these LacI- mutants exhibit a blue-plaque phenotype. These studies demonstrate that the error rate per nucleotide induced in the 182 known detectable sites of the lacI gene was 1.6 x 10(-6) for Pfu DNA polymerase, a greater than tenfold improvement over the 2.0 x 10(-5) error rate for Taq DNA polymerase, after approx. 10(5)-fold amplification. PMID- 1761219 TI - Nonradioactive labeling with chemically modified cytosine tails by the polymerase chain reaction. AB - We developed a modified nonradioactive method for the detection of DNA. This method makes use of the polymerase chain reaction for preparation of probes; that is, a DNA fragment inserted in the polylinker region of an M13 or pUC vector is amplified with primers that have a modified cytosine tail at the 5' terminus (C tailed primers). By this method, large amounts of labeled probes can be obtained easily. After hybridization, modified cytosine tails can be detected immunologically. DNA labeled by this method could be used in plaque hybridization. We could detect 0.05 pg of dot-blotted labeled DNA in 30 min with an enzyme-catalyzed chemiluminescence reaction. PMID- 1761220 TI - Pseudomonas aeruginosa plasmids as suicide vectors in Escherichia coli: resolution of genomic cointegrates through short regions of homology. AB - Pseudomonas aeruginosa plasmids which cannot replicate in Escherichia coli have been used to introduce specific modifications into the E. coli chromosome by homologous recombination ('gene targeting'). The E. coli gene (gpt) encoding guanine-xanthine phosphoribosyltransferase (Gpt) was used for initial targeting studies owing to the availability of a powerful positive selection for loss of the Gpt+ phenotype (6-thioguanine resistance or 6TGR or Gpt-). P. aeruginosa plasmids containing selectable markers flanked by gpt sequences were introduced as supercoiled DNA into an E. coli strain which contained a normal gpt locus. Primary cointegration of such plasmids into the E. coli genome results in a gene duplication event which maintains Gpt function; a secondary recombinational event which resolves the cointegrate either reverses the primary event or results in replacement of the original gpt copy with the modified version. A 316-bp region of homology was sufficient for cointegrate formation, and resolution of the cointegrates through a shorter (92 bp) homologous flank was selectable through loss of Gpt function. The frequency of cointegrate resolution under these conditions was significantly above the spontaneous gpt mutational loss rate. PMID- 1761221 TI - Bacillus subtilis inositol dehydrogenase-encoding gene (idh): sequence and expression in Escherichia coli. AB - The Bacillus subtilis inositol dehydrogenase (Idh)-encoding gene (idh) was cloned in the B. subtilis temperate phage, rho 11, and then in Escherichia coli plasmids (pBR322 and pUC118). The nucleotide sequence of the idh gene, which consists of 344 codons and whose product has an Mr of 38,351, was determined. E. coli, bearing pIOL05d15, in which expression of the idh gene is under the control of the lac promoter of pUC118, overproduced an active Idh to approx. 20% of total protein upon addition of isopropyl-beta-D-thiogalactopyranoside. This overproduced enzyme cross-reacted with an anti-Idh antibody, and exhibited the same Mr and substrate specificity as those of the B. subtilis enzyme. PMID- 1761222 TI - Nucleotide sequence and transcriptional start point of the kan gene encoding an aminoglycoside 3-N-acetyltransferase from Streptomyces griseus SS-1198PR. AB - We determined the nucleotide sequence of a 1794-bp BglII-BamHI fragment containing the kan gene (KmR) which encodes a novel aminoglycoside 3-N acetyltransferase of Streptomyces griseus SS-1198PR. The sequence was found to contain four open reading frames (ORF) in the direction of transcription determined by low resolution S1 nuclease mapping. Except for the largest one, these ORF are unlikely to be the coding sequence of kan, because of their inability to confer kanamycin resistance. The largest ORF could encode a 30.8-kDa protein consisting of 284 amino acids (aa) with 93.3 mol% G + C in the third position of codons, and is preceded by potential ribosome-binding sites. Thus, the largest ORF was likely to represent the kan gene. The transcription start point of kan was located 84 bp upstream from the start codon. The -10 region showed similarity to the Escherichia coli consensus promoter motif, while no sequence similarity was found in the -35 region. The deduced aa sequence of kan showed 85% similarity with that of the aacC7 gene of Streptomyces rimosus forma paromomycinus [Lopez-Cabrera et al., J. Bacteriol. 171 (1989) 321-328] suggesting that these genes are derived from a common ancestral gene. PMID- 1761223 TI - A dnaK homolog in the archaebacterium Methanosarcina mazei S6. AB - A fragment of genomic DNA cloned from the methanogenic archaebacterium, Methanosarcina mazei strain S6, was found to contain an 1857-bp open reading frame (ORF). A sequence matching the consensus ribosome-binding sequence determined for other methanogens was found upstream from the ORF. The amino acid (aa) sequence encoded by the ORF was compared with reference sequences and was found to be related to six DnaK sequences determined for five species of eubacteria (none exist for archaebacteria). The M. mazei S6 aa sequence was over 61% identical and over 77% similar (identities plus conservative substitutions) to the closest four reference sequences, which were all DnaKs. The gene described here is therefore proposed to be the first member of the dnaK family sequenced from the archaebacterial kingdom (Archaea). This finding confirms that DnaK proteins are highly conserved, occurring not only in eubacteria (Bacteria) and eukaryotes (Eucaria), but also in archaebacteria (Archaea). PMID- 1761224 TI - Nucleotide sequence and expression of the glucoamylase-encoding gene (glaA) from Aspergillus oryzae. AB - The glucoamylase-encoding gene (glaA) from Aspergillus oryzae was cloned using its cDNA as a probe, which had been isolated previously. From comparison of nucleotide (nt) sequences of genomic clones with its cDNA, the glaA gene was found to contain four short putative introns, 45-56 nt in length. The A. oryzae glaA gene shared 62% homology at the nt level with the A. niger glaA gene with the four introns located at the same position. The 5'-flanking region contained a TATA box at nt-72 from the start codon, and two putative CAAT sequences at nt-87 and -331. Genomic Southern analysis and physical mapping showed that the glaA gene is located on the smallest chromosome (3.4 Mb) of six separated bands of chromosomes. Clones containing the glaA gene, when re-introduced intro A. oryzae, resulted in a three- to eightfold increase in glucoamylase activity. PMID- 1761225 TI - Identification of eleven single-strand initiation sequences (ssi) for priming of DNA replication in the F, R6K, R100 and ColE2 plasmids. AB - Based on the ability to complement the poor growth of an M13 phage derivative lacking the complementary strand origin, eleven single-strand initiation sequences (ssi) for DNA replication are identified in the F, R6K, R100 and ColE2 plasmids. Six of them were from F, two from near the gamma and alpha origins (ori) of R6K, two from the vicinity of the basic replicon of R100 and one from near the ori of ColE2. They can be classified into two groups based on the morphology of the plaques and the length of nucleotide (nt) sequences required for ssi activity; one group that gives rise to larger and clearer plaques and can be reduced to nearly 100 nt (seven out of eleven), and another that generates smaller and less clear plaques and requires more than 200 nt for full activity (four out of eleven). Sequence homology is detected among some members from both groups. The possible biological roles of the ssi are discussed. PMID- 1761226 TI - Isolation and nucleotide sequence of the ribosomal protein S16-encoding gene from Aspergillus nidulans. AB - A genomic clone has been isolated from Aspergillus nidulans which is homologous to the ribosomal (r) protein S16-encoding gene of Saccharomyces cerevisiae (S16A) and the r-protein S19-encoding gene of rat (S19). The amino acid (aa) sequences, deduced from nucleotide (nt) sequence analysis, show that in both cases more than 63% of the aa are conserved. The proposed A. nidulans r-protein S16 gene (rps16) differs from that of S. cerevisiae in that it occurs as a single copy in the haploid genome (rather than two copies as in yeast) and contains two putative introns (rather than one). The mRNA leader is long compared to many Aspergillus genes, commencing 293 nt upstream from the coding region, and contains an open reading frame of 13 codons. PMID- 1761227 TI - Evidence for a new Escherichia coli protein resembling a lysyl-tRNA synthetase. AB - The amino acid sequence deduced from the nucleotide sequence of an open reading frame adjacent to the frdA gene of Escherichia coli shows 30.5% identity with the C terminus of Escherichia coli lysyl-tRNA synthetases. The three motifs characteristic of aminoacyl-tRNA synthetases of class 2 are recognizable within this sequence. PMID- 1761228 TI - Genetic analysis of the export of an extracellular DNase of Vibrio cholerae using DNase-beta-lactamase fusions. AB - A series of C-terminal deletions of the dns-encoded extracellular deoxyribonuclease (DNS) of Vibrio cholerae, fused to the mature form TEM beta lactamase (Bla) has been used to analyse the export of the DNase in both V. cholerae and Escherichia coli. All hybrid proteins were localized to the periplasmic space in E. coli and V. cholerae, with specific cleavage of the DNS Bla fusion occurring in V. cholerae. Periplasmic accumulation of wt DNS was also seen in V. cholerae when present on a multicopy plasmid. DNS fusions retaining all six Cys residues of DNS displayed both DNase and Bla enzymatic activity. While hybrid proteins were unable to be secreted across the outer membrane in V. cholerae, the cleaved (active) DNS portion of these proteins was exported. Taken together, these data suggest that the periplasmic form seen in E. coli is a normal intermediate also seen in V. cholerae, and that the lack of secretion machinery in E. coli prevents further export across the outer membrane. Although the DNS portion of the protein fusions must be able to interact with secretion genes, the whole fusion proteins are not exported. PMID- 1761229 TI - Isolation of Bacillus sphaericus biotin synthesis control mutants: evidence for transcriptional regulation of bio genes. AB - The genes involved in biotin synthesis have recently been isolated from Bacillus sphaericus [Gloeckler et al., Gene 87 (1990) 63-70]. Sequence analysis revealed that they are organized into two gene clusters, designated bioXWF and bioDAYB. The 5'-noncoding region of the bioD locus fused to the xylE reporter gene was inserted into the Gram-positive pUB110 replicon and the resulting plasmid was introduced into B. sphaericus IFO3525. Transformants expressed the xylE gene only if the biotin concentration in the growth medium remained below 50 ng/ml. After mutagenesis, colonies were screened for their ability to express the chromogenic marker in the presence of an excess of biotin. Most of these mutants escaped biotin repression of xylE gene expression. Classical genetic analysis showed they formed two main categories: chromosomal mutations, pleiotropically acting in trans on both bioXWF and bioDAYB 5'-noncoding regions, in which a 15-bp region common to both promoters represented a hot-spot for the second class of plasmid associated mutations. These results, completed by the identification of transcription start points for the bioD and bioX genes, strongly suggest that this 15-bp sequence overlaps the site of a biotin-mediated negative regulation circuit controlling the transcription of the bio genes. PMID- 1761230 TI - Identification and characterization of the ribosomal RNA-encoding genes in Clavibacter xyli subsp. cynodontis. AB - Clavibacter xyli subsp. cynodontis (Cxc) is a xylem-inhabiting bacterial endophyte of Bermudagrass. This organism is classified with Gram-positive, high G + C content, coryneform-actinomycete bacteria. Southern-blot analysis showed that Cxc contains only one copy of the ribosomal RNA-encoding genes (rRNA). A clone containing the rRNA genes was isolated from a genomic library of Cxc DNA cloned in the lambda EMBL3 vector. The gene cluster was partially sequenced, revealing the gene order 5'-16S-23S-5S-3', similar to that found in other prokaryotes. Low resolution S1 mapping suggested multiple transcription start points of the rRNA operon. PMID- 1761231 TI - Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. AB - Inducible resistance to lincomycin and macrolides in Streptomyces lividans TK21 results from expression of two linked genes: lrm, encoding a ribosomal RNA methyltransferase that confers high-level resistance to lincomycin with lower levels of resistance to macrolides, and mgt, encoding a glycosyl transferase that specifically inactivates macrolides using UDP-glucose as cofactor. The lrm and mgt genes have been cloned and sequenced. The deduced lrm product is a 26-kDa protein with much similarity to other ribosomal RNA methyltransferases, such as the carB, tlrA and ermE products, whereas the mgt product (predicted to be 42 kDa) resembles a eukaryotic glycosyl transferase. Macrolides that induce the lrm mgt gene pair are substrates for inactivation by the mgt product, and the lrm product confers ribosomal resistance to such inducers. PMID- 1761232 TI - Analysis of the promoter region of saf, a Streptomyces griseus gene that increases production of extracellular enzymes. AB - The product of the saf gene of Streptomyces griseus ATCC10137 mediated an increase in the production of several extracellular enzymes and retarded the formation of pigments and spores in Streptomyces [Daza et al., Mol. Gen. Genet. 222 (1990) 384-392]. A promoter upstream from saf was identified by subcloning a DNA fragment in the promoter probe pIJ486. Using the Escherichia coli Brevibacterium lactofermentum promoter-probe shuttle vector, pULMJ51, we determined that the saf promoter region is also active in E. coli. The transcription start points (tsp) of the saf promoter in Streptomyces and E. coli have been determined using high-resolution S1 mapping. The tsp are at the same position in both microorganisms. Expression from the saf promoter region was negatively regulated by phosphate in Streptomyces, but not in E. coli. The amplification of the saf promoter lacking the saf coding region did not increase the production of extracellular enzymes and did not reduce sporulation or pigmentation in Streptomyces (i.e., it does not titrate out a putative repressor of the genes encoding extracellular enzymes). Several structural features of the saf promoter region and saf mRNA are studied in relation to the regulation of the saf gene expression. PMID- 1761233 TI - The broad-host-range plasmid pTF-FC2 requires a primase-like protein for autonomous replication in Escherichia coli. AB - A 3202-bp fragment of plasmid pTF-FC2, cloned into PUC19, had previously been identified as the minimum region required for replication in either Pseudomonas aeruginosa or Escherichia coli polA- mutants. During the course of experiments to construct broad-host-range cloning vectors based on the pTF-FC2 replicon, it was found that the 3202-bp fragment had an absolute requirement for some function of the pUC19 vector. This requirement was eliminated in the presence of co-resident pTF-FC2 derivatives. An additional 1239-bp fragment from pTF-FC2, immediately adjacent to the 3202-bp fragment, was identified which restored the ability of the pTF-FC2 replicon to replicate autonomously. Sequence analysis of the region revealed a single open reading frame encoding a 40-kDa polypeptide, which was synthesised in an in vitro transcription/translation system. A comparison of the amino acid sequence of this protein with sequence data banks revealed limited homology with the RepB' primase of the IncQ plasmid, RSF1010. An M13 delta lac 110 replication-deficient phage system was used to demonstrate that the 40-kDa protein did function as a primase with respect to replication at the origin of replication (vegetative) of pTF-FC2. PMID- 1761234 TI - The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence. AB - Cells of Saccharomyces cerevisiae contain a major cytosolic cyclophilin (Cyp) related peptidyl-prolyl cis-trans isomerase (PPIase) which is the target for cyclosporin A (CsA) cytotoxicity and which is encoded by the CYP1 gene [Haendler et al., Gene 83 (1989) 39-46]. We recently identified a second Cyp-related gene in yeast, CYP2 [Koser et al., Nucleic Acids Res. 18 (1990) 1643] which predicts a protein with a hydrophobic leader sequence. A sequence lacking 33 codons from the 5'-end of the CYP2 open reading frame was generated by the polymerase chain reaction and engineered for expression in Escherichia coli. The corresponding recombinant truncated protein was purified and found to exhibit PPIase activity which was inhibited by CsA. The CYP2 gene is genetically unlinked to CYP1. As with CYP1, genomic disruption of CYP2 had no effect on haploid cell viability. Disruption of all three of the known yeast PPIase-encoding genes [CYP1, CYP2, and RBP1 for rapamycin-binding protein; Koltin et al., Mol. Cell. Biol. 11 (1991) 1718-1723] in the same haploid cell also resulted in no apparent cellular phenotype, suggesting either that none of these enzymes have an essential function or that additional PPIases can compensate for their specific absence. Whereas cells containing a genomic disruption of CYP1 exhibited a CsA-resistant phenotype, genomic disruption of CYP2 had no effect on CsA sensitivity. This suggests that the CYP1 gene product is the primary cellular target for CsA toxicity in yeast. Since both purified Cyps display CsA sensitivity in vitro, our data suggest that Cyp1 and Cyp2 differ in terms of their cellular function and/or localization. PMID- 1761235 TI - Protein disulfide isomerase is essential for viability in Saccharomyces cerevisiae. AB - Protein disulfide isomerase (PDI) is an enzyme involved in the catalysis of disulfide bond formation in secretory and cell-surface proteins. Using an oligodeoxyribonucleotide designed to detect the conserved 'thioredoxin-like' active site of vertebrate PDIs, we have isolated a gene encoding PDI from the lower eukaryote, Saccharomyces cerevisiae. The nucleotide sequence and deduced open reading frame of the cloned gene predict a 530-amino-acid (aa) protein of Mr 59,082 and a pI of 4.1, physical properties characteristic of mammalian PDIs. Furthermore, the aa sequence shows 30-32% identity with mammalian and avian PDI sequences and has a very similar overall organisation, namely the presence of two approx. 100-aa segments, each of which is repeated, with the most significant homologies to mammalian and avian PDIs being in the regions (a, a') that contain the conserved 'thioredoxin-like' active site. The N-terminal region has the characteristics of a cleavable secretory signal sequence and the C-terminal four aa (-His-Asp-Glu-Leu) are consistent with the protein being a component of the S. cerevisiae endoplasmic reticulum. Transformants carrying multiple copies of this gene (designated PDI1) have tenfold higher levels of PDI activity and overproduce a protein of the predicted Mr. The PDI1 gene is unique in the yeast genome and encodes a single 1.8-kb transcript that is not found in stationary phase cells. Disruption of the PDI1 gene is haplo-lethal indicating that the product of this gene is essential for viability. PMID- 1761236 TI - A single-copy promoter-cloning vector for use in Escherichia coli. AB - We have constructed and tested a single-copy-plasmid vector (pEU720) based on the IncFII-group plasmid, R100, that is useful for cloning promoters in front of lacZ. The vector is 15 kb long and contains a unique XhoI site in front of lacZ. PMID- 1761237 TI - [Chorea gravidarum]. AB - Chorea gravidarum is a rare maternal complication during pregnancy. Like the better known chorea minor it shows extrapyramidal symptoms with involuntary movements, lack of coordination, slurred speech and psychic disorders. The neurological state is normal except for a loss of muscle tone. The symptoms most commonly begin in the first trimester of pregnancy and usually resolve spontaneously after 2-3 months. The maternal mortality lies below 1%. In the case of subjectively disturbing symptoms anticonvulsive and sedative therapy with benzodiazepine or neuroleptics may be indicated. Etiological factors including rheumatic fever, chorea minor, hormonal, psychic and autoimmune disorders are discussed. Elective termination of the pregnancy is not indicated. The presented case report shows a chorea-like situation beginning in the ninth week of pregnancy. PMID- 1761238 TI - [Pregnancy and labor in advanced renal failure due to chronic pyelonephritis]. AB - The rare completion of a pregnancy in the presence of severe chronic renal failure is discussed in 6 cases. In all those cases the renal failure became worse, even though the pregnancy and delivery were satisfactory. Shortly after delivery, the 6 women underwent hemodialysis or peritoneal-dialysis. One patient died several weeks after delivery because of uremia. Our results suggest that for their own safety, women with severe renal failure should not become pregnant. PMID- 1761239 TI - [Prolonged pregnancy. Risks in pregnancy duration over 294 days and obstetric consequences]. AB - A total of 73 postterm pregnancies (greater than or equal to 294 days gestational age) were studied retrospectively and showed the following results: the frequency of postterm pregnancies was 1.5%. Compared to a control group of normal pregnancies (262-293 days), there was no evidence of a higher risk for infants born after term. As far as the different routes of delivery are concerned, there was a slightly higher number of cesarean sections and a markedly higher number of surgical vaginal deliveries in postterm pregnancies. PMID- 1761240 TI - [Vaccination against nonspecific bacterial vaginosis. Double-blind study of Gynatren]. AB - 167 patients suffering from nonspecific bacterial vaginoses were vaccinated in a double-blind, randomized, placebo-controlled trial. It appeared, during the study period of 14 months, that the vaccination with Gynatren, a lactobacillus vaccine, was significantly better than the placebo as concerns its therapeutical effect, but mainly as concerns its preventive effect (less reinfections). The vaccine was very well tolerated. We conclude that vaccination with Gynatren is an effective measure to prevent recurrences of nonspecific vaginosis. PMID- 1761241 TI - [Infection screening in pregnancy]. AB - The aim of screening for infectious diseases in pregnancy is to identify subjects who are at risk of a specific infection, which lends itself to effective intervention. The value of routine screening is determined by the validity of the test and the prevalence of the disorder in the population. During pregnancy, serological screening for rubella, syphilis, toxoplasmosis, HIV, hepatitis B and bacteriological screening for asymptomatic bacteriuria and gonorrhea is recommended. The search for additional infections is reserved for patients presenting special risk factors or clinical symptoms. PMID- 1761242 TI - [Surgical treatment of male baldness using Juri's crescent flap]. AB - This is a report on thirty six patients with male pattern baldness, surgically treated with one or two parieto-occipital flaps according to Juri. In six patients with isolated occipital baldness, specially designed flaps were used. Since male baldness usually is genetically determined and hairroots of the temporo-occipital scalp remain active throughout life, one can expect that they continue growing within the transposed flaps. There are three indications for parieto-occipital flaps: 1. psychological burden of the patient, 2. genetic background in the family of young patients, and 3. prior punch hair grafts whose roots have atrophied. PMID- 1761243 TI - [Possibilities in lower eyelid reconstruction]. AB - Reconstruction of the lower lid is associated with aesthetic and functional problems. Different techniques are proposed. From 1985 to 1988, 17 patients have been treated by a bridge flap technique from the upper lid combined with a composite graft from the septum. In our opinion, this method is indicated in smaller through-and-through defects as well as in total lid reconstruction. The advantages of the technique are discussed and demonstrated. PMID- 1761244 TI - [Concept and technique for closure of septum defects]. AB - A surgical concept for the closure of perforations of the septum is presented. Small and medium-sized defects are closed by a one-step extramucosal technique also used in rhinoplasties. Tissue tubes of mucoperichondrium, mucoperiosteum and the upper lateral cartilage are mobilized in both nasal lumina. Parts of the lamina quadrangularis are dissected and shifted to close the defect. Very large defects with a diameter of more than 3 cm are closed in a three-step technique. A spoon-shaped flap from the oral vestibule with a piece of ear cartilage attached is inserted into the perforation. The cartilage is covered with oral mucosa on both sides. These procedures are superior to traditional techniques in terms of both blood supply and safe closure. PMID- 1761245 TI - [Morphological changes in the healing process of mixed grafts in animal studies with reference to the immunological modification processes based on sex-specific chromosome analysis. A cytogenetic and histological study in rats]. AB - In the rat, free skin grafts exchanged between genetically different clones were completely rejected after three weeks. These transplants were not rejected when island autografts were set into preformed holes in the allografts. A typical graft-rejection pattern in the mixed skin transplants showed initial healing of the alloepidermis, which was later replaced by outgrowing autoepidermis from the interspersed islands. Since the autoepidermis covers the allocorium directly, it appears much like normal skin. In a few cases, connective tissue formed between the new autoepidermis and the remaining allodermis. Fibrous tissue streaks were also found between the otherwise unchanged allodermis layer and the muscle fascia. The remaining allocorium could still be found 111 days after transplantation using cytogenetic techniques and chromosome analysis. Mixed skin grafts consist of cell mosaics including cell lines form the donor and the recipient, with the corium structures completely retained. Cellular and humoral infiltration was not found to be part of the rejection process. PMID- 1761246 TI - [Electromyographic studies of myocutaneous sliding flaps for the covering of sacral decubitus ulcer]. AB - Gluteus maximus myocutaneous sliding flaps from one or both sides are useful in covering deep, usually infected sacral pressure sores. Although skin is known to tolerate higher pressure in the covered area, muscle offers far better conditions for flap healing of infected defects. In spite of excellent early results, the long-term fate of the transposed muscle remains uncertain. An electromyography study was performed on eleven patients out of 29 with sliding gluteus maximus myocutaneous flaps in periods up to seven months after surgery. Our results show that signs of denervation parallel reinnervation and functional integrity of the transposed muscle. PMID- 1761247 TI - [Finger tip amputations in children]. AB - Among the various alternative forms of treatment of digital tip amputations, replantation of the amputated tip as composite graft or conservative treatment (healing by secondary intention) are of special interest for the management of fingertip injuries in children. From 1986 until 1987, the authors treated thirteen fingertip amputations in children between one and eight years of age (mean 3.5 years). In twelve cases, the amputated tip was reattached as composite graft, one injury healed by secondary intention. Twelve children were reexamined according to a prospective protocol after a mean follow-up time of 3.4 years. In three cases, primary healing of the replanted tip could be observed, in eight cases partial necrosis and superficial mummification preceded complete healing. At follow-up, seven cases presented with an anatomical tip, four with a slight asymmetry. Distal phalangeal length was identical to the opposite side, but in two cases a maximal loss of length of 2 mm was observed. Fingernails showed no significant deformities, although nail bed injuries had occurred in 90% of the cases. Sensitivity was normal in all cases. Child and parents considered the final result excellent in 75% and good in 25%. Reattachment as composite graft or conservative treatment for management of fingertip amputations in children (Zone I to III according to Rosenthal) is recommended and discussed. PMID- 1761248 TI - [Ulnar head resection--indication and treatment results]. AB - A follow-up of 52 patients with a history of Darrach's procedure between 1961 and 1989 was carried out 16 years after surgery. 92% of those with trauma of the forearm, wrist, and distal radio-ulnar joint reported hardly any pain at all with marked improvement of forearm rotation and wrist mobility. The only drawback to surgery was an average strength loss of 50%. PMID- 1761249 TI - [Basket wires--a percutaneous surgical procedure for the treatment of unstable Colles' fractures]. AB - Colles fractures are usually treated with closed reduction and forearm plaster. Even if reduced perfectly, some of these fractures tend to redislocate dorsally and radially, requiring repeated reduction maneuvers. Since K-wires cannot be firmly anchored in the distal fragment if comminution exists, Kapandji proposed a method whereby the distal fragment is not pinned at all. He introduced the pins through the fracture itself and into the medullary canal of the proximal fragment, anchoring the wires into the opposite cortices of the radius shaft. In order to "pre-stress" the K-wires, Bohler and Zifko modified the technique and the wires themselves. They inserted the wires through small skin incisions into the fracture and into the proximal fragment as medullary pins. The specially bent pins glide smoothly into the medullary cavity and snugly fit along the distal fragment; thereby minimizing the chance of damaging extensor tendons. One pin is inserted proximal to Lister's tubercle and another radially, proximal to the radial styloid. Technique, indication, and possible technical errors are discussed based on the follow-up of forty one patients. PMID- 1761250 TI - [Intraoperative pressure measurement at the median nerve in carpal tunnel syndrome and its surgical significance]. AB - The authors measured the intraoperative pressures on the median nerve in local anesthesia in thirty patients. Pressures were recorded at the distal antebrachial fascia near the carpal tunnel, at the proximal and distal carpal tunnel and at the level of the palmar fascia distal to the carpal tunnel. The two passive and three active movements examined generally led to a pressure elevation. Passive movements had a greater effect on pressure at the proximal carpal tunnel. Active movements led to a high pressure level in the proximal and distal carpal tunnel higher than those observed during passive movements. Beneath the distal antebrachial fascia near the carpal tunnel, the pressure level was higher than beneath the antebrachial fascia at a greater distance from the carpal tunnel. Pressure levels beneath the distal antebrachial fascia correlated with the patient's age. Pressure values beneath the palmar fascia were low during passive and active movements. As a consequence, division of the flexor retinaculum and the distal antebrachial fascia up to 3 cm proximal of the carpal tunnel is necessary, whereas dissection of the palmar fascia distal to the carpal tunnel is not. PMID- 1761251 TI - Mean daily intake of volatile N-nitrosamines from foods and beverages in West Germany in 1989-1990. AB - The levels of volatile N-nitrosamines were determined in 38 alcoholic drinks and 215 food samples prepared for human consumption using standard culinary practices. The analyses used gas chromatography-thermal energy analysis. Detectable levels were found in 80 (31.5%) of the individual samples. The average daily intake of volatile N-nitrosamines in West Germany in 1989-1990 was found to be: 0.28 microgram N-nitrosodimethylamine (NDMA)/day, 0.011 microgram N nitrosopyrrolidine (NPYR)/day and 0.015 microgram N-nitrosopiperidine (NPIP)/day for men, and 0.17 microgram NDMA/day, 0.011 microgram NPYR/day and 0.015 microgram/NPIP/day for women. For men, 31% of the daily NDMA exposure results from the consumption of beer. PMID- 1761252 TI - Mean daily intake of primary and secondary amines from foods and beverages in West Germany in 1989-1990. AB - 264 samples of foods and beverages from the German market in 1989-1990 were analysed for primary and secondary amines. Amines were determined as benzenesulphonyl chloride derivatives by gas chromatography with chemiluminescense detection. The mean daily intake of primary amines was calculated to be 29 mg/day for women and 37 mg/day for men. For secondary amines, the mean daily intake was 6 mg/day for women and 8 mg/day for men. PMID- 1761253 TI - Safety evaluation of benzophenone. AB - Benzophenone (FEMA No. 2134; CAS No. 119-61-9) was administered in the diet to rats at target dose levels of 20 mg/kg body weight/day for 90 days and 100 or 500 mg/kg/day for 28 days. Body weights and food consumption were measured weekly; haematology, clinical chemistry and urinalysis values were obtained at 4 wk and at the end of the study. Gross and microscopic pathological examinations were conducted and organ weights were recorded. Treatment-related changes occurred in erythrocyte count, haemoglobin, haematocrit, bilirubin, total protein and albumin at the mid- and high-dose levels, although all changes did not occur in both groups in both sexes. There were indications of increased absolute and relative liver and kidney weights in the mid- and high-dose groups, but this was not statistically consistent for absolute kidney weights. Histopathology of the liver in the mid- and high-dose groups showed hepatocellular enlargement with an associated clumping of cytoplasmic basophilic material around the central vein. A no-effect level was demonstrated at 20 mg/kg/day for 90 days of administration. This would be equivalent to an intake of 1200 mg/day for a 60-kg human. On the basis of the calculated Possible Average Daily Intake of 0.33 mg/day, a safety factor of greater than 3600 is demonstrated. The safety factor based on the more realistic per capita consumption of 0.32 microgram/day would be approximately 3.7 million. PMID- 1761254 TI - Quantitative relationship between oral nitrate-reducing activity and the endogenous formation of N-nitrosoamino acids in humans. AB - Salivary nitrate and nitrate concentrations, in vitro kinetics of nitrate reduction in saliva, and numbers of salivary nitrate-reducing micro-organisms were each compared with N-nitrosoamino acid excretion in 16 humans eating controlled diets. N-Nitrosoproline (NPRO) and N-nitrosothiazolidine-4-carboxylic acid (NTCA) excretion were measured after intake of nitrate (5.24 mmol) and L proline (4.35 mmol) before and after treatment with an oral antiseptic (Peridex, 0.12% chlorhexidine gluconate). Peridex treatment resulted in a 94% reduction in the numbers of salivary nitrate-reducing bacteria, a decline from 17 to 4% in the amount of salivary nitrate that was reduced to nitrite in vivo, and an 85% reduction in the rate of in vitro nitrate reduction by saliva. Concurrently, there were 62 and 74% inhibitions of endogenous NPRO and NTCA formation, respectively. Correlations of the numbers of nitrate reductase micro-organisms, in vivo oral nitrate reduction and salivary nitrite concentrations, with individual NPRO excretion, indicated that individuals with higher oral nitrate reducing capacities formed more N-nitrosoamino acid endogenously. These data suggest that individual differences in oral nitrate reduction are a significant factor in gastric nitrosation and account for a large proportion of the interindividual variability in nitrosoamino acid excretion. PMID- 1761255 TI - Liver response to low-hexachlorobenzene exposure in protein- or energy-restricted rats. AB - The individual effects of protein deficiency and energy restriction on liver response to low-hexachlorobenzene (HCB) exposure were investigated in adult male Wistar rats. In rats fed either the low-protein or control diet, the only effect caused by HCB was a decrease in paralysis time following an ip injection of zoxazolamine. This decrease was similar for both groups. In the animals subjected to energy restriction, HCB induced a greater decrease in paralysis time, an increase in the size of centrilobular hepatocytes, a lower liver DNA content and an increased concentration of HCB in the adipose tissue, compared with the control and protein-deficient groups. Our data suggest that energy restriction increases liver response to HCB, while protein deficiency does not impair the hepatic reaction to small doses of HCB exposure. PMID- 1761256 TI - Effect of emodin on cooked-food mutagen activation. AB - The herbs Rheum palmatum B and Polygonum cuspidatum S are frequently used as laxatives and anticancer drugs in Chinese medicine. The antimutagenic activity of these herbs as well as their active component emodin was examined in Salmonella typhimurium TA98. The crude extracts and emodin induced a dose-dependent decrease in the mutagenicity of benzo[a]pyrene (B[a]P), 2-amino-3-methylimidazo[4,5 f]quinoline (IQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Furthermore, emodin reduced the mutagenicity of IQ by direct inhibition of the hepatic microsomal activation and not by interaction with proximate metabolites of IQ and/or by modification of DNA repair processes in the bacterial cell. PMID- 1761257 TI - Chronic oral toxicity and carcinogenicity study of thiabendazole in rats. AB - The potential toxicity and carcinogenicity of thiabendazole (TBZ) was investigated in F344 rats. TBZ was given in pelleted diets at different dietary levels (0, 0.05, 0.1, 0.2 or 0.4%) to groups of 30 rats of each sex for 104 wk. Throughout the study, a marked decrease in body-weight gain was observed in males and females fed 0.4% TBZ. Transitional cell hyperplasia of the renal pelvis and/or papilla was observed in dosed groups of each sex with significant positive trends. Low incidence of transitional cell papilloma or carcinoma of the urinary system was recorded in the dosed groups. Preputial gland adenoma occurred in males treated with 0.4% TBZ, and the incidence was significantly higher than in controls. There was no clear-cut evidence of the carcinogenic activity of TBZ in the urinary system of male and female rats. PMID- 1761258 TI - Effect of chlorophyllin on mercuric chloride-induced clastogenicity in mice. AB - The effect of chlorophyllin (1.5 mg/kg body weight) on the clastogenicity of mercuric chloride (HgCl2) was studied in vivo in mouse bone marrow cells. HgCl2 (3.0, 6.0 and 12.0 mg/kg body weight) administered by gavage induced chromosomal aberrations at frequencies directly proportional to the dose. Chlorophyllin was not clastogenic, and significantly reduced the mitotic index when given alone. Chlorophyllin administered simultaneously with HgCl2 significantly reduced the frequencies of chromosomal aberrations in a dose-dependent manner. When given simultaneously with the lowest HgCl2 concentration tested (3.0 mg/kg body weight), chlorophyllin provided total protection. A lower degree of protection was given by chlorophyllin administered 2 hr before HgCl2. The data demonstrate the potential of green plant components to modify the genotoxic activity of HgCl2 when administered orally. PMID- 1761259 TI - Safety evaluation of alkaline cellulase. AB - A programme of studies was conducted to establish the safety of alkaline cellulase, an enzyme used as a processing aid in the food industry. Laboratory animal studies were used to assess general, inhalation and reproduction toxicity, eye irritation and skin irritation and sensitization. Mutagenic potential was assessed in microbial and animal in vivo studies. The pathogenicity of Humicola insolens, the micro-organism used in the production of alkaline cellulase, was also assessed in laboratory animals. Basic ecotoxicity in a variety of test species was studied. General toxicity by a variety of routes was low; there was no evidence of reproductive toxicity. There was evidence of mild skin irritation and some eye conjunctival reddening. There was no evidence of skin sensitization, mutagenic potential, ecotoxicity or notable pathogenicity. When these results are considered along with levels of human exposure and previously published data, it appears that alkaline cellulase is safe for consumers in the given applications, requires no special occupational health precautions in manufacture, and is of low environmental impact. Furthermore, the micro-organism used in production of alkaline cellulase has no notable pathogenicity. PMID- 1761260 TI - [What is the contribution of PET in tumor diagnosis today?]. AB - Positron emission tomography (PET) permits qualitative and quantitative measurements of tumor metabolism in the patient. In the clinical setting, the present studies suggest that tumors with a potential for proliferation can be differentiated from scar tissue, soft tissue and benign lesions. Accumulation of tracer by lymph nodes identifies them as metastatic. On the basis of a quantification of the accumulation of tracer and its metabolites, information can be provided about the biological activity of a tumor, and presumably also about the prognosis. The response of a tumor to treatment can be monitored, in particular in combination with CT. Possible selection of resistant parts of the tumor can be determined, so that modification of treatment is possible. Modes of application can also be individualized by identifying pre-treatment advantages of intraarterial or systemic administration; recurrent tumors can be detected with a high degree of accuracy. However, to date, only limited numbers of cases are available, so that, in view of the very promising aspects of this modality, more widespread application followed by the evaluation of larger numbers of patients is needed. PMID- 1761261 TI - [Diagnosis of focal liver lesions. The value of imaging systems]. AB - Selection of the suitable modality for the detection or differential diagnosis of focal liver lesions must consider, in addition to its accuracy, such factors as on-site availability, the costs involved, and the stress to the patient. The preferred screening technique is ultrasonography which, however, has a high failure rate, in particular in the case of small lesions. In many cases computed tomography (CT) permits the correct diagnosis to be established. Both CT and ultrasonography make possible selective percutaneous biopsy. Magnetic resonance imaging is one of the most sensitive procedures, but is often not available - even in specialized centers. With this technique or blood pool scanning, hepatic hemangiomas found incidentally can be diagnosed in 90% of the cases. The diagnosis of focal modular hyperplasia continues to be difficult. PMID- 1761262 TI - [Diagnosis of gastroenterologic diseases with sonography. Part 1: Principles- ultrasound diagnosis of diffuse and local liver damage]. AB - Ultrasonography has now become an integral part of the gastroenterological diagnostic work-up and treatment. In some clinical problems it may be employed as the sole procedure, for example in the diagnostic evaluation of gallstones, for measuring the size of the liver and spleen, or in the detection of free fluid within the peritoneal cavity. Among the diffuse lesions of the liver, macronodular cirrhosis and typical forms of fatty liver can be diagnosed ultrasonographically, while the majority of such diffuse changes are not amendable to ultrasonographic evaluation. Cystic lesions of the liver are often diagnosable with ultrasonography, while many circumscribed solid lesions, such as metastases or focal-nodular hyperplasia, pose a differential diagnostic problem. PMID- 1761263 TI - [Digital luminescence radiography. Part 1: Basic principle, technical execution and clinical use]. AB - Digital luminescence radiography (DLR) is a new technique in projection radiography, which enables the production of plain X-ray images and motion tomographies with high quality, and is suitable for digital image management. With this procedure the X-ray image produced by conventional roentgen devices is temporarily stored on a reusable photostimulable storage phosphor screen which is characterized by a wide dynamic range. A laser beam scans the exposed phosphor screen and recovers the stored X-ray information as photostimulated luminescence radiation. A photomultiplier converts the emitted light into electrical signals. After normalization and digitization the signals are transmitted to an image processor. The stored digital image can be individually processed and displayed, digitally archived or transferred to any location. The technique is described in two following papers. Part 1 covers the basic principle of the system and the technical implementation of the data acquisition with its advantages and disadvantages as compared with conventional film/screen radiography. PMID- 1761264 TI - ["Excessive" lowering of blood pressure. Are there diastolic blood pressure values which should not be breached?]. PMID- 1761265 TI - [Aquarium--when hobby becomes a danger. A case report]. AB - In this case report, allergic rhinitis and episodes of asthma triggered by the hemoglobin of the red mosquito larva used as fish food are described. After three years of contact and an allergic condition persisting for three months, skin testing and IgE determination revealed moderate sensitization of the immediate reaction type. When contact with the allergen was stopped, the symptoms abated immediately. PMID- 1761266 TI - [Cytostatic drugs. Part 5 (conclusion): Other cytostatically active drugs]. PMID- 1761267 TI - [Fixed drug combination of ACE inhibitor plus diuretic. Results of an open multicenter study for the treatment of hypertension]. AB - An open multicenter trial involving 7,232 participating physicians, was performed to assess the anti-hypertensive efficacy and tolerance of a fixed combination of captopril and hydrochlorothiazide (Capozide) given once daily to 34,976 patients (mean age 58.5 +/- 11.4 years) with mild-to-moderate hypertension inadequately controlled by previous anti-hypertensive treatment. After 8 weeks, the response rate to a daily dose of Capozide 25 or 50 was 87.2%. Within this period, the mean systolic/diastolic blood pressure dropped from 175 +/- 16/103 +/- 5 mmHg to 150 +/- 13/88 +/- 7 mmHg (p less than 0.001). In 81% of the questionnaires, treatment with the combination was rated superior to the previous treatment; in only 5% was it considered inadequate. Side effects, for the most part mild, were reported by 7.4% of the patients. Treatment with Capozide was discontinued, or another form of treatment substituted in 12.9% of the cases. PMID- 1761268 TI - [Formal thought disorders and speech disorders in schizophrenia--new findings from empirical studies?]. AB - The investigation of formal thought and speech disorders in schizophrenia is hampered by the missing differentiation of speech and thought. Empirical investigations paying attention to this differentiation do not argue for specific schizophrenic speech or thought disorders but for a clinically relevant continuum of these disorders within the group of endogenous psychoses. PMID- 1761269 TI - [Psychobiology of compulsive disease]. AB - The predominant psychobiological hypotheses regarding the pathophysiology of obsessive-compulsive disorder (OCD) are that a selective basal ganglia dysfunction and a dysregulation of one or several central serotonin (5-HT) subsystem are related to at least some aspects of the syndrome. Recent neuroanatomical, -pharmacological, and -ethological studies indicate a complex perceptual and cognitive role for the basal ganglia, particularly the striatum and the pallidum, in addition to the well-established motor functions. Obsessive compulsive symptoms in syndromes with extrapyramidal-motor dysfunction, such as Gilles de la Tourette syndrome or Chorea minor (Sydenham), response to specific pharmacotherapy, behavioural therapy, and psychosurgery, as well as findings derived from brain imaging studies including positron emission tomography (PET) support the view of a frontal cortex/basal ganglia dysfunction in OCD. In addition, growing evidence suggests that potent inhibitors of 5-HT reuptake and other 5-HT subsystem-selective agents, such as the azapirones with partial agonist properties at the 5-HT1A receptor, are effective in OCD not only has improved the therapeutic perspective but may also reveal clues to the aetiopathogenesis of OCD. Much of this evidence has resulted from the discovery of multiple receptors and signal transduction pathways for 5-HT and from experiments relating the action of 5-HT receptor-selective agents to discrete effects in different subsystems. Among these 5-HT subsystems the 5-HT1D and 5 HT1A receptor-effector system complex appears to play a central role in the pathophysiology of OCD symptoms and the mechanism of action of antiobsessional drugs. Recent psychoneurobiological findings are reviewed briefly and evaluated in the context of the 5-HT and basal ganglia hypothesis of OCD. PMID- 1761270 TI - [Neurologic and psychiatric manifestations of lead poisoning in adults (case report and review of the literature)]. AB - A 59-year-old potter presented with lead polyneuropathy after 37 years of occupational exposure. There was a 25-year history of normochromic normocytic anaemia with moderate basophilic stippling, mild renal failure, hyperuricaemia and abnormal porphyrins. Since 1964 three short psychotic episodes were noted. Cranial computed tomography showed extensive bilateral symmetrical calcification in the cerebellar hemispheres and slight calcification in the subcortical area of the cerebral hemispheres and basal ganglia. T2-weighted magnetic resonance imaging disclosed high signal intensities in the periventricular white matter, basal ganglia, insula, posterior thalamus and pons. Differential diagnostic aspects are discussed with special regard to CT and MRI findings. A review of the literature on neurological and psychiatric manifestations of lead intoxication in adults is given. PMID- 1761271 TI - [Flashback following use of cannabis--a review]. AB - The present study tries to find an answer to the question, whether the consumption of cannabis can cause flashbacks, and, if so, under what circumstances they occur. This is of interest for the treatment, prognosis and also from the legal viewpoint. The definition of a flashback is often unclear. Empirical investigations are often not sufficiently comparable, the supplementary data are very often missing, making the evaluation of the results difficult. Self diagnosis by the consumer is usually unsuitable for estimating the frequency and phenomenology of flashbacks. Cannabis may trigger flashbacks after consuming hallucinogenes; the probability of the occurrence of a flashback seems to increase with the amount of hallucinogenes a person has consumed. A definite correlation between the amount of hashish consumed and the occurrence of flashback does not exist. Flashbacks have also been reported after consuming cannabis alone. However, data vary regarding the frequency of such flashbacks. According to the available data they occur rarely and require a thorough differential diagnostic evaluation in each individual case. As a rule, the occurrence of a flashback may take place in cases where there is an intake of hallucinogenic drugs in the recent case history. PMID- 1761272 TI - [Mood follow-up over 6 years in a patient with season-dependent form of depression (SAD)]. AB - Since the first description of seasonal affective disorder (SAD), many international studies have confirmed the existence of this subgroup of depressive patients. Even though the diagnosis of SAD has been incorporated into the DSM-III R classification system, many psychiatrists maintain a certain skepsis as to the existence of SAD as a separate sub-group of depression. The diagnostic issues are important because of the apparent specificity of treatment of SAD with bright light. Most diagnoses have relied on retrospective descriptions of the patients' depressive and healthy phases with respect to time of year. We present prospectively gathered weekly depression self-ratings in a SAD patient over a period of six years that may provide valid criteria for diagnostic purposes. This is a particularly exemplary case with implications for the relationship between light therapy and the course of depressive phases, the possible interaction of light treatment with lithium, the relationship between weight-changes and mood changes over the year and aspects of family loading of the illness. PMID- 1761273 TI - [Lyme borreliosis--epidemiology, etiology, diagnosis and therapy]. AB - The tick-borne Lyme Borreliosis may lead to a wide variety of sequels. Besides symptoms involving skin, joints and heart the infection provokes as a neurologic complication a meningopolyneuritis Garin-Bujadoux-Bannwarth in second state and a progressive encephalomyelitis in third state. Unexpected widespread--as modern laboratory investigations proved--the contamination only occasionally inflicts clinical manifestations. Involvement of the nervous system is substantiated by the demonstration of endogenous Borrelia antibodies in the cerebrospinal fluid. This prove is to claim especially for the assumption of a third state neuroborreliosis with progressive encephalomyelitis. Severe damage can be prevented by prompt diagnosis, specific treatment and follow-up. PMID- 1761274 TI - [The neurologic department of the Neurologic Clinic--establishment of the Heidelberg Chair for Neurology 1881-1969]. AB - During the 20th century clinical neurology developed to a fully established discipline being descended from Psychiatry and Internal Medicine. In this paper the development of clinical neurology at the University of Heidelberg from a Nervenabteilung at the clinic for internal medicine to a chair with separate clinic of neurology is outlined as an example for the controversy which accompanied the institutionalization of the discipline in Germany. Pointing out motives and arguments of the persons involved in this process the specific circumstances of the development of neurology in Germany are stated more precisely. PMID- 1761275 TI - Circadian variations and extraadrenal effect of ACTH on insulinemia in rabbit. AB - The present experiment was designed to study the action of ACTH1-24 on insulin secretion during the circadian cycle in normal rabbits and to provide evidence that ACTH1-24 has an extra-adrenal effect on this secretion. In normal rabbits intravenous administration of three doses of ACTH1-24 (1, 10, 100 micrograms/kg) at 10 a. m. increased plasma insulin levels. Hyperglycemia only occurred with doses of 10 and 100 micrograms/kg. A maximum insulin response was already obtained at 1 micrograms/kg. The same experiment performed at 12 p. m. also induced hyperinsulinemia which was only noted at 10 and 100 micrograms/kg; hyperglycemia was only observed after stimulation by the highest dose (100 micrograms/kg). ACTH was therefore more effective during the day; however, at 12 p. m. plasma insulin levels were the highest, but only with the maximum dose of ACTH (100 micrograms/kg). The effect of ACTH1-24 was evaluated throughout the day on normal and adrenalectomized rabbits. In normal animals injection of ACTH1-24 increased plasma glucose and insulin levels both together. In the contrary, in rabbits deprived of adrenal glands, ACTH1-24 induced high insulinemia along with hypoglycemia. We could, therefore, reasonably conclude that ACTH stimulates directly the pancreatic secretion of insulin. PMID- 1761276 TI - Food intake after hatching inhibits the growth hormone induced stimulation of the thyroxine to triiodothyronine conversion in the chicken. AB - The effect of a single injection of 10 micrograms chicken GH on circulating thyroid hormones as well as in vitro liver 5'-monodeiodination (5'-D) activity was studied in posthatch chicks submitted to different feeding conditions. One group was normally fed after hatching, a second group was only fed after three days and a third group was food deprived after 2 days of feeding. Combination of all results indicates that the start of food intake abolishes the stimulatory effect of a GH injection on circulating T3 and liver 5'-D activity. Food deprivation after a period of food intake restores the GH effect on plasma T3 but not on liver 5'-D. PMID- 1761277 TI - Failure to demonstrate natriuretic activity in the posterior pituitary after immunoneutralization of the vasopressin content. AB - The attempt to demonstrate the presence of a natriuretic substance in the posterior pituitary after immunoneutralization of the AVP content failed. Rats infused i.v. AVP-immunoneutralized posterior pituitary extract did not respond by natriuresis to a saline infusion, in contrast to those infused untreated posterior pituitary extract. Thus, vasopressin seems to be the natriuretic substance in the posterior pituitary extract. PMID- 1761278 TI - Transitory coexistence of oxytocin and vasopressin in the hypothalamo neurohypophysial system of parturient rats. AB - We used in situ hybridization and immunocytochemistry to investigate a possible coexistence of vasopressin and oxytocin in hypothalamic neurons of parturient rats. We found that a fraction of magnocellular neurons in the paraventricular and supraoptic nuclei contained immunostaining for both peptides as well as oxytocin and vasopressin mRNA hybridization. Colocalization of immunoreactive vasopressin and oxytocin could be observed in some of the Herring bodies in the median eminence and the posterior lobe. No coexistence of vasopressin and oxytocin was found in pregnant or in lactating animals, indicating that the observed coexistence is transitory, perhaps mediated through changing hormonal conditions peri partum. PMID- 1761279 TI - Does estradiol treatment normalize the hypothalamic-pituitary-adrenal axis in streptozotocin-induced ovariectomized diabetic female rats? AB - We recently found circulating corticosterone (CS) levels to be significantly lower in diabetic female rats as compared with proestrous control animals. This reduction in CS was correlated with the hypoestrogenic state of the diabetic female. It was the purpose of this study to evaluate basal and corticotropin releasing hormone (CRH)-stimulated CS secretion in ovariectomized (OVX) control (C) and streptozotocin-induced diabetic (D) rats given blank, 5 mcg and 20 mcg estradiol (E2) implants to determine if adrenal CS secretion in the diabetic is normalized by E2 treatment. After 3 weeks of diabetes, pituitary-adrenal function was assessed in rats from each group with a CRH stimulation test. The remaining rats were sacrificed for determination of CS, E2, testosterone and fructosamine in serum. Suppressed CS secretion in OVX female diabetic rats was partially restored with E2 therapy. Basal CS levels were significantly higher in 20 mcg E2 treated C and D rats compared with OVX rats. However, C rats had significantly higher basal CS compared with D rats in similarly E2 treated groups. The CS response to CRH stimulation was not different between OVX female diabetic and control rats. Estrogen enhanced the CS response to CRH stimulation in control animals but not in diabetic animals suggesting altered estrogen action at the pituitary level in diabetic animals. PMID- 1761280 TI - The effect of guanidino substances from uremic plasma on insulin binding to erythrocyte receptors in uremia. AB - We have studied insulin binding to erythrocyte receptors in a group of 25 nonobese, nondiabetic uremic patients undergoing maintenance hemodialysis for 2 54 months and 14 healthy controls. Erythrocytes of predialyzed uremics bind significantly less insulin than control erythrocytes (p less than 0.01). Dialysis resulted in a rapid increase of insulin binding (p less than 0.001). The concentrations of plasma insulin and glucose remained essentially unchanged during 5-hour hemodialysis and did not significantly differ from the control values. The down regulation of insulin receptors in undialyzed patients in the presence of normal plasma insulin concentration indicates that factors other than insulin itself could be responsible for insulin receptor activity during uremia. The results demonstrated that creatinine, creatine and glycocyamine have a direct suppressive effect on insulin binding of postdialyzed plasma (p less than 0.05) in concentration of 1 mmol/l. This suggested that specific uremic toxins could play an important role in the mechanisms of altered insulin binding during hemodialysis. Despite the high concentration of these compounds in blood of uremics, the only common feature for these compounds is the presence of the guanidino group in the molecule. PMID- 1761281 TI - Insulin secretion, glycosylated haemoglobin and islet cell antibodies in cystic fibrosis children and adolescents with different degrees of glucose tolerance. AB - In comparison with 12 weight-matched controls, 39 children and adolescents with cystic fibrosis (CF) showed higher fasting glycaemic levels and both delayed and enhanced blood glucose responses to OGTT. Glycaemic response was normal in 30/39 patients (76.9%), impaired in other 7 cases (18%) and diabetic in the remnant two (5.1%). Fasting insulin levels and total insulin output during OGTT did not differ in patients and controls, but insulin peak in CF group was delayed and sustained. In the whole CF series mean HbA1c was higher than in controls but no difference was found between patients with normal and those with impaired glucose tolerance. Islet cell antibodies were absent in the entire CF group. In conclusion, our results confirm the raised prevalence in CF of glucose tolerance abnormalities, which do not seem to depend on auto-immune factor involvement. Delayed insulin response to OGTT can be considered a very early expression of beta cell impairment in the course of CF. In our experience HbA1c assay did not constitute a sensitive and specific screening test for detection of the C patients with glucose intolerance. PMID- 1761282 TI - Studies on facial temperature rise and involvement of serotonin in the respiratory stimulation by CRH. AB - Following an intravenous injection of 100 micrograms hCRH a facial flushing can frequently be observed along with respiratory stimulation. Both effects can be mediated by a common transmitter. Serotonin is well known to produce facial flush as well as to modulate respiration. In order to clarify is serotonin is a common mediator for facial flush and respiratory stimulation after i.v. application of hCRH, we studied the time course of facial skin temperatures and respiratory stimulation after intravenous injection of 100 micrograms hCRH in 10 healthy subjects. Furthermore, we measured respiratory stimulation after i.v. administration of 100 micrograms hCRH in 10 healthy subjects pretreated with the serotonin antagonist cyproheptadine. Facial skin temperatures reached maximum levels 9 min after CRH administration and remained raised for more than 60 min. Respiratory stimulation occurred within the first minute after CRH administration and reached a maximum during the second minute, but could no longer be observed after 10 min. Serum serotonin levels did not change after CRH stimulation in doses up to 3 micrograms/kg body weight), and cyproheptadine did not abolish the respiratory stimulation effect of hCRH in a dosage sufficient to suppress CRH. induced cortisol secretion. PMID- 1761283 TI - Blood glucose, serum thyroid hormones, insulin, C-peptide and C-peptide/insulin ratio in hyperthyroid patients. PMID- 1761284 TI - Acute effect of propranolol on the growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism. PMID- 1761285 TI - Carcinomatous infiltration of the thyroid presenting as thyroiditis and stridor. PMID- 1761286 TI - Biological parameters of bone remodelling in chronic adrenal insufficiency. PMID- 1761287 TI - Effect of prednisolone on urate and oxypurine excretion. PMID- 1761288 TI - Impedance analysis applicable to cardiac muscle and smooth muscle bundles. AB - An electrical equivalent circuit was constructed to represent a chain of five myocardial cells in a cardiac muscle bundle with various degrees of cell-to-cell coupling, and an impedance analysis was performed. The impedance across the entire network was measured at frequencies ranging from 10(1) to 10(6) Hz. The Bode plots were nearly superimposable for 1, 10, and 100 tunnels; for 10(3), 10(4), and 10(5) tunnels, the absolute zeta at 10 Hz was lower: e.g., 9.82 M omega for 1 tunnel compared to 6.64 M omega for 10(5) tunnels. The delta zeta 1/2 values were shifted to the left in the well-coupled cases: e.g., for 1 tunnel, f1/2 was 37.8 kHz, and for 10(5) tunnels, f1/2 was 1.2 kHz. For high coupling, the Bode plots contained a double component due to the end membranes. When Ro was increased by eight times, zeta increased by 7.47 fold (for 1 tunnel, 10 Hz), and by 3.72 fold (for 10(5) tunnels, 10 Hz). Raising Ro to x 12, x 100, and x 1000 produced a further and further shift to the left of the Bode plots. The total tissue resistivity (Rt) increased as a function Ro. Thus, in low coupling cases, almost all of the applied current passes through the interstitial space; e.g., at 1 tunnel (10 Hz), 1.0% of the current passes through the cell pathway (Rcell). The ratio of impedances at 10 kHz to 10 Hz (zeta 10kHz/zeta 10Hz) decreased with increasing tunnels (for Ro x 1). The ratio of resistivities at Ro x 8 to Ro x 1 (Rt'/Rt) was 7.47 for 1 tunnel. In contrast, the ratio at 10(5) tunnels was 3.73. It is concluded that it is difficult to determine the degree of cell coupling from such impedance analysis, unless the same tissue can be used for its own control, i.e., before and after a large change in cell coupling is introduced. PMID- 1761289 TI - A reduced sampling schedule for estimating the parameters of the glucose minimal model from a labeled IVGTT. AB - The minimal model of tracer glucose disappearance allows the measurement in man of important metabolic parameters from a labeled IVGTT (intravenous glucose tolerance test). Usually 30 blood samples are drawn to measure the insulin and the labelled glucose concentration time courses, which provide the data base for the model identification. In this paper, we address the problem of reducing the number of blood samples withdrawn without, however, deteriorating parameter estimation. By using a stepwise approach, largely based on optimal experiment design theory, we have derived a reliable reduced sampling schedule, which comprises only 14 total samples. The practical application of this reduced schedule has been validated by applying it in a new set of human experiments, completely independent of the ones used in the design phase. PMID- 1761290 TI - A three-dimensional thermal and electromagnetic model of whole limb heating with a MAPA. AB - Previous studies by the authors have shown that if properly implemented, the Pennes assumptions can be applied to quantify bioheat transfer during extremity heating. Given its relative numerical simplicity and its ability to predict temperatures in thermoregulated tissue, the Pennes model of bioheat transfer was utilized in a three-dimensional thermal model of limb heating. While the arterial blood temperature was assumed to be radially uniform within a cross section of the limb, axial gradients in the arterial and venous blood temperatures were computed with this three-dimensional model. A realistically shaped, three dimensional finite element model of a tumor-bearing human lower leg was constructed and was "attached" mathematically to the whole body thermal model of man described in previous studies by the authors. The central as well as local thermoregulatory feedback control mechanisms which determine blood perfusion to the various tissues and rate of evaporation by sweating were input into the limb model. In addition, the temperature of the arterial blood which feeds into the most proximal section of the lower leg was computed by the whole body thermal model. The variations in the shape of the tissues which comprise the limb were obtained from computerized tomography scans. Axial variations in the energy deposition patterns along the length of the limb exposed to a miniannular phased array (MAPA) applicator were also input into this model of limb heating. Results indicate that proper positioning of the limb relative to the MAPA is a significant factor in determining the effectiveness of the treatment. A patient specific hyperthermia protocol can be designed using this coupled electromagnetic and thermal model. PMID- 1761291 TI - A device to measure the cross-sectional area of soft connective tissues. AB - A device has been designed and fabricated to measure the cross-sectional area of soft connective tissues ex vivo. It consists of two displacement transducers; one sensing tissue thickness and the other sensing width. Outputs are recorded (via an analog to digital interface) using a personal computer. Numerical integration of a thickness versus width plot computes cross-sectional area. This plot also provides a quality check of acquired data. This device has been successfully used in biomechanical studies of rabbit patellar tendons, rat medial collateral ligaments, and dissected specimens of human fascia. PMID- 1761292 TI - Sound velocity inversion in layered media with band-limited and noise-corrupted data. AB - With reflection data measured from two different incident angles, it is possible to make them "nearly the same" by stretching or contracting the time axis of one of them. In this way, a correspondence is built up between the two travel times, which can be used to calculate the one-dimensional sound velocity profile of the medium. For the special case that the impulse response of the medium consists of sparse spikes, a spectral fitting procedure is developed which deconvolves the received signal, and gives the exact positions of the spikes. The stepwise sound velocity profile can then be calculated from these positions. In experimental measurements the plane wave assumption made in the analysis is not true, but this can be accommodated with some modifications of the calculation. Results of both computer simulation and of measurements are presented, indicating the validity of these processings. PMID- 1761293 TI - Inspiration produced by bilateral electromagnetic, cervical phrenic nerve stimulation in man. AB - Eddy-current stimulation of both phrenic nerves at the base of the neck in human subjects was carried out to provide inspiration resulting from tetanic diaphragm contraction. The inspired volume obtained was in excess of spontaneous tidal volume. PMID- 1761294 TI - The effect of CO2 laser pulse repetition rate on tissue ablation rate and thermal damage. AB - The ablation rate and thermal damage in skin produced by a superpulsed CO2 laser operating at pulse repetition rates between 1 and 900 Hz was measured. When delivering a fixed number of pulses (20 or 30) of equal energy, a 55-60% increase in the amount of tissue ablated was observed when the pulse repetition rate rose from 10 to 200 Hz. At pulse repetition rates greater than 200 Hz no further increase was seen. Under identical conditions, an 80% increase in the zone of thermal damage was observed when the pulse repetition rate was increased from 1 to 60 Hz. The large increases in tissue ablation and tissue damage may indicate the existence of a layer of mixed-phase (i.e., liquid and vapor) or metastable liquid which can store significant amounts of thermal energy between pulses. The data suggest that CO2 lasers should be operated at relatively low repetition rates for optimal performance. PMID- 1761295 TI - A 16-channel 8-parameter waveform electrotactile stimulation system. AB - We have developed a general-purpose electrotactile (electrocutaneous) stimulation system as a research tool for studying psychophysiological performance associated with various stimulation waveforms. An experimenter-defined command file specifies the stimulation current and waveform of each of the 16 channels. The system provides burst onset delay of 0-20 ms, phase current of 0-50 mA, interphase interval of 0-1000 microseconds, number of pulses per burst from 1 100, pulse repetition rate of 0.1-25 kHz, phase width of 2-1000 microseconds, and functionally-monophasic pulses (with zero dc current) or balanced-biphasic pulses (with equal positive and negative phases). The system automatically delivers the desired stimulation, prompts the subject for responses, and then logs subject responses. Key features of the system are 1) very flexible choice of bursts of pulsatile waveforms, 2) real-time control of all of the waveform parameters as mathematical functions of external analog inputs, and 3) high-performance electrode-driver circuitry. PMID- 1761296 TI - Control of end-point forces of a multijoint limb by functional neuromuscular stimulation. AB - A multivariable feedback controller was designed and tested for regulating the magnitude and orientation of the force vector at the end point of a multijoint limb in contact with an isometric load. The force vector was produced by electrical stimulation of muscles. To achieve arbitrary control of end-point force magnitude and orientation, two coupling issues must be dealt with by the control system. First, there is a geometric coupling between the end-point force vector and joint torques. The amplitude and orientation of the force vector depend on the limb geometry. Second, torques at two joints may be coupled due to activation of muscles that cross them (biarticular coupling). To eliminate the geometric coupling, a transformation of controller error from the Cartesian space to the joint space was employed. A multivariable proportional-plus-integral (PI) control law was used to calculate muscle activation based on the transformed controller error. Centralized and decentralized controls were investigated for decoupling the effects of biarticular muscles. The results obtained from cat experiments showed that the magnitude and orientation of the end-point forces of the cat hindlimb could be regulated by this controller. In the presence of strong biarticular coupling, centralized control yielded better performance than decentralized control during transient responses. Both control strategies could decouple the biarticular muscle at steady state. When no biarticular coupling was present, centralized control sometimes performed worse than decentralized control. This is the first step in the simultaneous control of multiple joints by functional neuromuscular stimulation (FNS). The controller has broad potential applications in FNS neural prostheses. PMID- 1761297 TI - Tunable diode laser spectroscopy for isotope analysis--detection of isotopic carbon monoxide in exhaled breath. AB - A high resolution tunable infrared diode laser spectroscopy system was developed for isotope analysis with sensitivity at ppb levels. Such a system is ideally suited for detection and measurement of minute amounts of infrared active compounds present in a huge noninfrared active background such as air. The operation and capabilities of the system were demonstrated by measuring physiological levels of isotopic carbon monoxide, 12C16O and 13C16O, naturally present in exhaled human breath with essentially no sample preparation. The simplicity in obtaining such data suggests that fundamental physiological information may be derived from noninvasive measurements. This makes the system potentially useful for many biomedical applications. PMID- 1761298 TI - Development of medical pressure and temperature sensors employing optical spectrum modulation. AB - Fiber optic Fabry-Perot sensors have been developed whose optical reflectance varies with optical cavity depth (pressure) or with change in a material's refractive index (temperature). These sensors employ a unique combination of features: they are interrogated by an LED; they are designed to operate within a single reflectance cycle; and their returned light is analyzed by a dichroic ratio technique. The sensors use a step index glass fiber and are relatively insensitive to absolute light levels and fiber bending. They have an expanded linear operating range and can be built for low cost disposable applications. Sensor performance meets or exceeds established medical requirements. PMID- 1761299 TI - Computer simulations of activation in an anatomically based model of the human ventricular conduction system. AB - Simulations of the electrical activity during excitation were performed in an anatomically based model of the human ventricular conduction system. Each of the 33,000 elements of this model represented a unit bundle of Purkinje or atrioventricular nodal tissue. The Ebihara-Johnson model for sodium defined the active membrane characteristics. Using a combination of new and existing modeling techniques, simulations of excitation were completed in approximately 5 min CPU time on an IBM 3090 at the Cornell National Supercomputer Facility. Activation times at sites in the model were compared to experimental measurements for the excitation of the ventricular myocardium on the endocardial surface. These "literature-based" times were estimated from a number of reported human heart mapping studies. Initially, the times fit poorly. The major factor for the discrepancy was the conduction velocities of the elements, which were a result of the physical and electrical parameters derived from a review of histologic and electrical properties studies. In addition, there was a latency between activation of the system in the left ventricle of the model and that in the right ventricle when compared to the experimental work. When the times were scaled to adjust for the conduction velocity and ventricular latency effects, the match between the simulation and literature-based times was much improved. Quantitative comparison between normalized times resulted in correlation coefficients CCF = 0.76 for the right ventricle and CCF = 0.64 for the left ventricle. PMID- 1761300 TI - Structural complexity effects on transverse propagation in a two-dimensional model of myocardium. AB - A thin sheet of cardiac tissue was modeled as a set of resistively coupled excitable cables with membrane dynamics described by the modified Beeler Reuter model. Transverse connections have a resistance Rn and are regularly distributed with a spacing delta on any given cable, to provide alternating input and output junctions. Flat wave longitudinal propagation corresponds to propagation along a single continuous cable since all units of the network are functionally isolated due to the absence of transverse current flow. Events on a given cable during flat transverse propagation include electrotonic spread of potential from input to output junctions, action potential initiation at input junctions, and collision at output junctions. The propagating two-dimensional transverse wavefront is an undulating transmembrane potential surface with highs at the input junctions and lows at the output junctions. The action potential upstroke is also modulated in a periodic manner with minimum and maximum Vmax at the input and output junctions respectively. Thus, the network is capable of a diversity of dynamic behavior spatially distributed in relation to the specific pattern of transverse connections chosen. Overall, the behavior of the network model is in good agreement with available structural and electrophysiological data on myocardium. In addition, this network topology allows to handle more easily parameters governing propagation and to avoid very large matrices which are costly in computational effort and overall computer time. PMID- 1761301 TI - [Diagnosis of infections with gene technology methods: an increased value of miasmata?]. PMID- 1761302 TI - [The "polymerase chain reaction" (PCR) and its possible applications]. AB - This review article summarizes the basics of PCR technology. Besides technical details PCR as a diagnostic tool for infectious diseases is described. Finally problems involved in using this technique for the diagnosis of infectious diseases are discussed. PMID- 1761303 TI - [Applications of PCR in molecular immunology]. AB - Since a wide panel of monoclonal antibodies specific for antigen receptor variable (V) regions is unavailable, PCR has emerged as the primary analytical method for determining the expressed repertoire of T- and B-lymphocyte populations. Furthermore, PCR amplification of immunoglobulin V-region genes is exploited for the production of monoclonal antibodies by repertoire cloning as a replacement of the B-cell-hybridoma technique and for the humanization of murine monoclonal antibodies. The heavy and light chains of immunoglobulins as well as the transmembrane-protein chains which build the heterodimeric T-cell receptors consist of a constant and of an antigen-binding variable segment. Conventional PCR makes use of two specific oligonucleotide primers that flank a sequence of interest to prime replication of the bracketed DNA. In the case of antigen receptor encoding DNA one flanking sequence of the variable region is unknown or heterogeneous. Therefore, modifications of the conventional PCR had to be developed for the cloning and analysis of antigen-receptor DNA: (1) the usage of known V-gene segments by a lymphocyte population can be analyzed by quantitative PCR with panels of V-specific primers; (2) since PCR primers do not have to be completely complementary to the target DNA, it is possible to amplify a variety of different V regions with degenerate primers for relatively conserved sequences of the V genes; (3) enzymatic addition of a homopolymeric dG tail to the variable end of the antigen receptor DNA makes the amplification completely independent of the structure of the variable region because the dG-tailed DNA can be amplified with a nonspecific poly-dC oligonucleotide combined with a specific primer for the constant gene segment of interest. PMID- 1761304 TI - Is it fair? PMID- 1761305 TI - Health insurance, 1979-1989: the frayed connection between employment and insurance. AB - Using data from the Current Population Survey, this article shows that low-income workers were much less likely to have employer-sponsored insurance in 1989 than they were in 1979. For example, workers earning $6.00 per hour in 1989 were over 10 percentage points less likely to have employer sponsored health insurance than were workers earning $3.51 per hour in 1979 (the constant dollar equivalent of $6.00 per hour in 1989). The decline in employer sponsored coverage was confined to low income workers; coverage levels did not decline for workers earning $30,000 per year and more. The paper explores two types of explanations for the decline in coverage among low-income workers. First, the decline might have resulted from increases in the price of medical care, the cost of administering health insurance, and from a breakdown in the small group insurance market. Second, the decline might have resulted from changes in the structure of the economy that changed the types of jobs available to low-income workers. Since coverage declines among the self-employed parallel coverage declines among the employed, it seems likely that increases in the price of health insurance are a larger part of the cause for coverage declines than are changes in the structure of the economy, but further research on this question is needed. PMID- 1761306 TI - A lifetime perspective on proposals for financing nursing home care. AB - In this paper data from the National Mortality Followback Survey and the National Nursing Home Survey are used to estimate the lifetime cost of nursing home care. The expected discounted cost for persons turning 65 in 1990 is $27,600. However, variation around this average is high. The 9% of persons expected to use at least 5 years of nursing home care will account for 64% of aggregate cost for the cohort; the 68% using less than 3 months of care will account for only about 1% of cost. The percentage of costs covered under alternative financing strategies also varies widely. An entitlement covering the first 3 months of care subject to 30% coinsurance would cover 5% of aggregate cost; an entitlement with a 2-year deductible and the same coinsurance would cover 41% of cost. PMID- 1761307 TI - Medicare patient access to posthospital skilled nursing facility care. AB - The willingness of nursing homes to accept any Medicare admissions (Medicare participation) and the number of patients they serve (Medicare utilization) affect the access of Medicare SNF patients to posthospital care. Characteristics of facilities, their market areas, and state Medicaid reimbursement were found to affect both participation and utilization. Most important, when Medicaid and private nursing home market conditions support high-intensity care, facilities are more likely to serve Medicare patients and admit more of them. SNFs in states that require Medicare certification are more likely to accept Medicare admissions, suggesting that the cost and effort of achieving certification are a barrier to service to Medicare SNF patients. For-profit facilities, hospital based SNFs, and larger nursing homes have higher rates of participation and serve more Medicare patients when they serve any. PMID- 1761308 TI - The resource utilization group system: its effect on nursing home case mix and costs. AB - Using data from 1985 and 1986, we examine how New York state's prospective payment system affected nursing homes. The system, called Resource Utilization Group (RUG-II), aimed to limit nursing home cost growth and improve access to nursing homes by "heavy-care" patients. As in Medicare's prospective hospital reimbursement system, payments to nursing homes were based on a "price," rather than facility-specific rates. With respect to cost growth, we observed considerable diversity among homes. Specifically, those nursing homes most financially constrained by the RUG-II methodology exhibited the slowest rates of cost growth; we observed higher cost growth among the homes least constrained. This higher rate of cost growth raises a question about the desirability of using a pricing methodology to determine nursing home payment rates. In addition to moderating cost growth, we also observed a significant change in the mix of patients admitted to nursing homes. During the first year of the RUG-II program, nursing homes admitted more heavy-care patients and reduced days of care to lighter-care patients. Thus, through 1986, the RUG-II program appeared to satisfy at least one of its major policy objectives. PMID- 1761309 TI - Family structure and physicians' hours in large, multispecialty groups. AB - There is a consensus that male physicians work more hours than female physicians, but no consensus on how or why female physicians limit hours. Drawing on a new national survey of physicians in large, multispecialty groups, we conclude that much of the hours differential is due to differences in nonpractice incomes and is likely to be permanent. However, due to reductions in family responsibilities for women and increases in nonpractice incomes for men, the differential should narrow somewhat as the current cohort of physicians ages. We also infer that the link between hours and practice choices may well account for much of the diversity of the literature. PMID- 1761310 TI - Rollover effects in gatekeeper programs: cushioning the impact of restricted choice. AB - Public and private medical care plans that restrict the beneficiary's choice of providers have experienced rapid growth in the past decade as a means to contain costs and coordinate care. Such plans have been criticized for engendering beneficiary dissatisfaction and potentially impeding access to necessary care. Some of the objections to primary care "gatekeeping" may be diminished by recruiting the physician who served previously as the beneficiary's "usual source of care" to assume the role of formal gatekeeper. This study examines how persons whose gatekeepers were their regular source of care before plan implementation differed in their use and satisfaction from persons required to change their regular source of care. Our findings indicate that satisfaction was significantly higher among individuals who experienced no change in usual source of care. These individuals also tended to be less likely to use the emergency department as a source of care. Although the data are from Medicaid managed care programs, the findings may also be applicable to private sector point-of-service plans that adopt the primary care gatekeeper model. PMID- 1761311 TI - Medicaid shortfalls and total unreimbursed hospital care for the poor, 1980-1989. AB - This article examines the relationship between Medicaid payments and hospital costs from 1980 through 1989, using data from the American Hospital Association's Annual Survey of Hospitals. It finds that payments covered about 90% of Medicaid hospital costs until 1985, then declined to 78% in 1989. Together, Medicaid shortfalls ($4.2 billion) and unsponsored care ($8.9 billion) accounted for $13.1 billion in unreimbursed hospital costs in 1989. Most of the recent growth in unreimbursed hospital cost incurred in care for the poor is now caused by rising Medicaid shortfalls rather than increases in unsponsored care. While Medicaid shortfalls accounted for about one-fifth of unreimbursed care for the poor in 1980, they accounted for a third in 1989. PMID- 1761312 TI - Employer-sponsored insurance coverage for alcohol and drug abuse treatment, 1988. AB - This paper uses 1988 Bureau of Labor Statistics data to analyze the content of insurance coverage for alcohol and drug abuse treatment offered by medium and large private sector firms. Ninety percent of workers had medical insurance. Of these, 81% had coverage for alcohol abuse treatment and 75.5% had coverage for drug abuse treatment. The coverages were almost always offered together, and the benefits were generally identical for both. Coverage for inpatient detoxification was most common, followed by outpatient care and inpatient rehabilitation. Self insured plans, although exempt from state-mandated benefits, were as likely to include alcohol and drug abuse coverage as Blue Cross and Blue Shield and commercial plans, and their specific benefits were no less generous. Coverage limitations tended to be more restrictive for these illnesses than for others. The nature of the limitations varied greatly, although day and dollar limits were most common for inpatient treatment, and visit limits and higher copayments were most common for outpatient treatment. PMID- 1761313 TI - Health insurance coverage of the immigrant elderly. AB - In this paper, I examine and contrast factors that contribute to whether individuals are covered by public health insurance (Medicare, Parts A and B, with and without Medicaid benefits) or private insurance. The study, based on data from a sample of foreign- and native-born elderly, employs descriptive analysis and a multivariate investigation involving logistic regression models. The results show that the immigrant population is less likely than native-born elderly to be covered by public insurance or to have private insurance. Medicare coverage for the immigrant elderly is strongly influenced by their length of stay in the United States, employment status, and country of origin, while their having private insurance coverage is affected by race, income, and employment status. For native-born elderly, race, income, and employment status are contributing factors to the type of insurance coverage retained. Policy implications are discussed. PMID- 1761314 TI - Estimating county percentages of people without health insurance. AB - County data on the percentage of people without health insurance are seldom available, although state program planning requires such information. As part of an evaluation of Washington's Basic Health Plan (BHP), we conducted a telephone survey in nine Washington counties to estimate the percentage of people under the age of 65 who were uninsured. We used regression analysis to estimate the percentage uninsured in a county as a function of the percentage unemployed. Two validation approaches yielded very good results, suggesting that the equation could be used to estimate the percentage uninsured in unsurveyed counties. The variation ranged from 15% to 23% uninsured in the 9 surveyed counties, and was estimated to range from 9% to 35% among the state's 39 counties. With proper caution, estimates based on this equation can probably be used in other states if better data are unavailable. PMID- 1761315 TI - Communication with Alzheimer's patients: an analysis of caregiver listening patterns. AB - Alzheimer's Disease is the leading cause of dementia in today's aging population. Behavioral manifestations of this illness have been studied primarily by focusing on diagnostic and assessment tests. Communication studies have emphasized identification of speech and language deficits, and little attention has been given to communication processes that are still in place. This study addresses caregiver listening responses as they occur in conversations with an Alzheimer's patient. This project videotaped twenty-six episodes of conversations between caregivers in an adult day health care setting. The dialogue was transcribed (enhanced by the use of video-taped data) and analyzed for caregiver listening responses. Frame analysis was used to identify several categories of caregiver's responses to the patient's message. In addition, this study found that sensitive listening and partial entry into the patient's frame (reality) may be an effective response to prevent behavior and anxiety related outbursts. This study also found that videotaping of natural conversations and frame analysis can be useful tools for continued study in the treatment and care of Alzheimer's patients. PMID- 1761316 TI - Information-seeking triggered by age. AB - Age labels may lead to the seeking of age-stereotypic information from target individuals. Using Carver and de la Garza's information-seeking procedure (which asked respondents to judge the relative importance of various kinds of information they would glean from drivers involved in an automobile accident for assigning accident responsibility), but extending it to a wider life span (16 to 91 years of age) and to both genders, we generalized earlier findings to a similar undergraduate sample (n = 437) in another country. Also demonstrated for the first time is the fact that ageist information-seeking across the life span was independent of the driver's gender, the participant's age, and the participant's gender. Specifically, participants wanted to know from younger drivers about their driving conduct (whether they had been drunk and speeding), and from older drivers about their capacity for driving (mental competence, vision, and health). The seeking of environmental information (car safety and road conditions) did not vary with the age of driver in any systematic way. PMID- 1761317 TI - Throwing patterns of older adults: a follow-up investigation. AB - Previous investigations of the movement patterns of older adults have focused on functional movements. Performance declines have been reported with increasing age. Many investigations, however, do not require older adults to perform maximal, force producing actions. Smaller declines might be observed if older adults made a maximal effort. This investigation examined changes in a maximal skill--the overarm throw for force. Active, older adults were videotaped as they threw tennis balls. Thirteen people were filmed for two consecutive years. Gender and age differences were examined for movement patterns, ball velocity, and selected kinematic measures. Participants threw using patterns and velocities generally observed in children in middle elementary-school years. This result suggested there was a decline in this force production skill. Some older adults regressed in the movement patterns they used over the two years of testing. Older males threw faster, using more advanced movement patterns than older females. PMID- 1761318 TI - Usefulness of commercial memory aids as a function of age. AB - Recent research has produced disagreement about the usage and usefulness of external memory aids across age groups. The present study examined the use and perceived usefulness of commercial memory aids as a function of the ages of users and potential users. Three age groups (ages 20, 45 and 65 years) were asked to indicate whether they owned each of thirty different commercial aids and regardless of ownership, to rate the degree of usefulness of each of the aids. Each age group used certain aids or perceived certain aids as more useful, than did other age groups. The pattern of results suggest that memory aid usage differs with age partly because the memory tasks required of a person change with life stage. PMID- 1761320 TI - Can disturbances of the ejaculatory sequence contribute to male infertility? PMID- 1761319 TI - Individual differences in reminiscence among older adults: predictors of frequency and pleasantness ratings of reminiscence activity. AB - Although reminiscence has been recognized as an adaptive coping mechanism and its beneficial value is stressed in later life transitions, few studies have examined the frequency of self-reported reminiscence in relation to the personality traits, psychological well-being, purpose in life, and background characteristics of elderly individuals. Nor has there been any previous attempt to study the independent contributions of these factors as predictors of the frequency of reminiscence activity or the pleasantness ratings of the reminiscence activity. A sample of seventy individuals between the ages of sixty-seven and eighty-two years was selected from community settings, and an equivalent age sample of seventy individuals was selected from nursing home settings. A structured interview procedure and questionnaire assessed the frequency of reminiscence activity and ratings of pleasantness associated with it. The independent contributions of various personality measures, psychological well-being measures, and meaning of life measures as predictors of the frequency and pleasantness of reminiscence activity were analyzed via multiple regression analyses. The results showed that despite wide variability in the use of reminiscence, certain specific factors of personality, psychological well-being, will to meaning, and negative life events are strong predictors of the frequency and pleasantness of reminiscence activity. These results are discussed in terms of mental health implications for the identification of individuals with greatest potential for engaging frequently in reminiscence as a therapeutic tool and finding it a pleasant pursuit. PMID- 1761321 TI - Sperm transport in the human female reproductive tract--a dynamic interaction. AB - The interaction between sperm and the human female tract has been largely ignored. This review summarizes the data available from animal species with specific reference to sperm in the oviduct. Our knowledge of sperm transport within the human female tract is explored and, using the data available from animal species, three lines of future experimental design are suggested. Firstly, there is the need to improve and develop techniques to recover sperm successfully from the tract. Second, an in-vitro approach which examines the modulation of reproductive tract fluids on sperm function is advocated. Third, an in-vitro tissue/cell culture system is required to investigate in more detail the interaction between the epithelium and sperm. Using such approaches many of the questions posed in this review can be addressed confidently in the near future. PMID- 1761322 TI - Movement characteristics and hyperactivation of human sperm on different epithelial cell monolayers. AB - Studies of sperm movement characteristics concern mainly sperm swimming between two glass surfaces (as in the Makler chamber). Using automated videomicrography, (CellSoft, Cryo Resources, New York, USA), we have analysed the movements of human sperm swimming on monolayers of different origins: monkey kidney (Vero) cells, bovine oviduct cells, and human endometrial cells. About 10(5) sperm were deposited upon preparations consisting of monocellular layers adhering to a coverglass, and placed in a deep slide-coverglass system. Experiments were first performed at room temperature then at 37 degrees C. At room temperature, motion characteristics on Vero cell layers (six samples) were not different from those measured in either the conditioned or corresponding non-conditioned media, except for the amplitude of lateral head displacement (ALH) which was significantly lower. Comparison of the three different cell monolayers showed no difference between them for the corresponding motion parameters. The data were dramatically different at 37 degrees C: sperm swimming on cell monolayers of genital origin (oviduct or endometrium) exhibited high rates of hyperactivation (HA: 36.7% and 38.6% respectively), which was significantly more than on either Vero cells (10.9%) or in a control medium (12.6%). Moreover, HA rates were significantly higher on genital cell monolayers than in the corresponding conditioned medium. Hyperactivated sperm exhibited lasting 'star-spin' trajectories rather than 'transitional phases'. It is concluded that passage of sperm on either oviduct or endometrial epithelial cell monolayers can induce sperm hyperactivation and improve their fertilizing capacity. PMID- 1761323 TI - The fertility potential of male cystic fibrosis patients. AB - Men suffering from cystic fibrosis (CF) are considered to be infertile because of azoospermia. In testicular biopsies from two patients with CF normal spermatogenesis was found despite the absence of sperm in the ejaculate. Fructose and prostaglandin were not detectable in the semen whereas the levels of acid phosphatase and zinc were within normal limits, indicating normal prostatic function and absence of seminal vesicles. These findings may improve the possibility for male patients with CF to father a child. PMID- 1761324 TI - Effects of LHRH-analogue treatment of spermatogenic dysfunction in the dog. AB - Three male dogs, aged 2-4 years, which exhibited a high percentage of sperm with abnormal tails in their semen and low levels of peripheral plasma LH and testosterone were given two injections of 400 micrograms an LHRH analogue (LHRH A) 3 h apart. The semen quality of all three dogs and the peripheral plasma levels of LH and testosterone were examined in two of the dogs. Plasma levels of LH and testosterone in both dogs peaked at 30 and 90 min respectively, after the injection of LHRH-A. The semen quality of all three dogs had improved temporarily 20 days after the injection. To be specific, although the mean percentage of sperm with abnormal tails in the three dogs was 19, 26 and 32% respectively before injection of LHRH-A, these values had decreased to 10, 16 and 13%, respectively, 20-40 days later. Thereafter, however, the percentage sperm abnormalities increased again. The testes and epididymides of two of the dogs were examined histologically at the end of 90 days. Sloughed germ cells were observed in the seminiferous tubules of the testes, and pyknotic epithelial cells were noted in some of the epididymal ducts. The other dog, which had a history of three unsuccessful matings was treated again with LHRH-A and mated with three bitches 30, 75, and 110 days later, respectively. Only the bitch mated with this dog 30 days after a second series of injections conceived. It is assumed that the semen quality of the three dogs improved because of a temporary rise in plasma LH and testosterone levels after the injection of LHRH-A. It is concluded that the fertility of dogs with a high percentage of sperm with abnormal tails can be improved approximately 30 days after treatment with an LHRH-A. PMID- 1761325 TI - Does unilateral orchidectomy influence blood flow, microcirculation and vascular morphology in the remaining testis? AB - Adult rats were hemi-orchidectomized and various aspects of testicular blood flow, microcirculation and vascular morphology were studied in the remaining testis after 30 days and compared to that in intact sham-operated animals. Testis weight, total testicular blood flow (measured with microspheres), capillary blood flow pattern (studied with laser Doppler flowmetry) and the volume of interstitial fluid in the testis (index of vascular permeability) were all unaffected by hemi-orchidectomy. Morphometric measurements on perfusion-fixed testicular tissue showed that the volume densities of Leydig cells, blood vessels and small exchange blood vessels were increased by hemi-orchidectomy (by approximately 45, 33 and 42%, respectively). The volume density of Leydig cells in individual testes was correlated to the volume and surface density of capillaries + small postcapillary velules (r = 0.72 and 0.86, respectively). Hemi orchidectomy is known to result in a doubling in testosterone secretion per Leydig cell. This increased endocrine activity results in moderate increase in the vascular exchange area but other aspects of testicular microcirculation and blood flow are apparently unaffected. PMID- 1761326 TI - Seminal emission by electrical stimulation of the spermatic nerve and epididymis. AB - The spermatic nerve and epididymis were stimulated electrically in dogs to elucidate the possibility of artificial seminal emission after bilateral transection of the hypogastric nerves and sympathetic trunks. Before transection, electrical stimulation of a distal end of the severed spermatic nerve caused a trace amount of emission in two dogs and no emission in the remaining four. In contrast, 1 month after the transection, stimulation of a distal end of the severed spermatic nerve caused seminal emission in all six dogs examined, with full seminal volume in four dogs and partial volume in the remaining two. Anatomically, sympathetic nerves originating from the upper portion of the lumbar sympathetic ganglia descended along the spermatic arteries to the testes as spermatic nerves. The present results indicate that spermatic nerves have the potential to generate seminal emission as a compensatory pathway after bilateral transection of the hypogastric nerves. Both direct and percutaneous electrical stimulation of epididymal tails resulted in a full volume of seminal emission in all dogs with transection of both hypogastric nerves and lumbosacral sympathetic trunks as well as in unoperated controls, while high voltage (8 V vs 40-80 V) was required to cause seminal emission by electrical stimulation on the skin surface. Direct stimulation of epididymal tails in men undergoing orchidectomy as treatment for prostatic carcinoma or during biopsy of the contralateral testis in a patient with a testicular tumour, resulted in seminal emission in all five epididymides examined either from the end of the severed vas deferens or in the posterior urethra if the vas deferens was not severed. PMID- 1761327 TI - Testicular lesions and lymphocyte subpopulations in rats immunized with a soluble fraction of testicular homogenate. AB - A soluble fraction obtained from a testicular homogenate by precipitation with ammonium sulphate (ASPM) was emulsified with Freund's complete adjuvant (CFA) and injected into Wistar rats. At 50 days after the first immunization (total of three injections) the animals had developed moderate and multifocal testicular damage, characterized mainly by sloughing of the seminiferous epithelium. A delayed-type hypersensitivity response and circulating antibodies to ASPM were detected at different times with maximum levels at 50 days. The addition of Bordetella pertussis to the immunization did not increase the severity of the lesion but augmented the cellular and humoral immune response to ASPM. The phenotypic characterization of cells present in the lymph nodes draining from the site of immunization in animals injected with CFA alone (control group) revealed an increase in CD8+ T-cells and a low CD4/CD8 ratio. Conversely, rats immunized with CFA plus ASPM (experimental group) exhibited testicular damage and showed a significant decrease in CD8+ cells with a normal CD4/CD8 ratio. In conclusion, rats immunized with a testicular antigen developed focal aspermatogenic lesions and a concomitant specific immune response as well as lymph-node cell variations focused apparently on the CD8+ T-cell subpopulation. PMID- 1761328 TI - Advances in pacing for bradycardia. PMID- 1761329 TI - Clinical cardiac electrophysiology: the last 10 years. PMID- 1761330 TI - Parasympathetic overactivity and its evaluation in patients with sinus nodal dysfunction. AB - In 17 controls, and 17 patients with sinus nodal dysfunction, an electrophysiologic study was made of sinus nodal function and atrioventricular nodal conduction in the basal state. The study was then repeated in all patients after atropine. The heart rate, mean sinus cycle length, variations of sinus cycle length, sinus node recovery times, sinuatrial conduction time, AH interval, and atrioventricular nodal Wenckebach threshold were significantly different in patients from those of controls. All these parameters changed significantly in patients after atropine, and were comparable to those of controls except for the atrioventricular nodal Wenckebach threshold. Atropine failed to increase the heart rate beyond 90 beats per minute in 10 of 17 patients (sensitivity of 59%) or by at least 30% above the resting heart rate only in 4 of them (sensitivity of 24%). The variations of sinus cycle length, and their standardized value, could detect sinus nodal dysfunction with sensitivities of 59 and 47%, respectively. From our results, we conclude that there is parasympathetic overactivity in patients with sinus nodal dysfunction. Because of their very low sensitivities, the atropine test and variations of sinus cycle length were not useful in identifying sinus nodal dysfunction noninvasively. The normal response of the heart rate to atropine does not exclude sinus nodal dysfunction, but atropine may help to differentiate abnormalities intrinsic and extrinsic to the sinus node during the electrophysiologic study. PMID- 1761331 TI - Posture determines the nature of the interaction between angiotensin converting enzyme inhibitors and loop diuretics in patients with chronic cardiac failure. AB - The effects of inhibition of the renin angiotensin aldosterone system on the natriuretic and diuretic actions of an intravenous dose of frusemide 40 mg in patients with chronic cardiac failure maintained on oral diuretics were studied in the supine and erect positions. In the patients studied in the supine position the total 4 hour diuresis was decreased from 995 (92) ml to 668 (66) ml and the total 4 hour natriuresis fell from 105 (14) mmol to 67 (14) mmol following the administration of captopril. Creatinine clearance fell from 87 (8) ml/minute to 52 (15) ml/minute. In the patients studied in the erect position the total 4 hour diuresis was 596 (87) ml without captopril and 562 (83) ml with captopril. Total 4 hour natriuresis was 71 (13) mmol without captopril and 65 (9) mmol with captopril. Creatinine clearance was reduced by captopril from 82 (7) ml/minute to 47 (12) ml/minute. The reduction in the diuretic and natriuretic response to frusemide caused by captopril in the supine position is mediated through a fall in glomerular filtration rate. However, in the erect position, which is associated with even further increases in activity of the renin angiotensin aldosterone system, the reduction in diuresis and natriuresis that a fall in glomerular filtration rate would cause is offset by abolition of the rise in sodium retaining hormones, angiotensin II and aldosterone that mediate the antinatriuretic effect of the erect position. PMID- 1761332 TI - Indirect assessment of acute effects of ethyl alcohol on coronary circulation in patients with chronic stable angina. AB - Acute effects of ethyl alcohol on left ventricular performance, haemodynamic and electrocardiographic response to treadmill exercise test were studied in 20 patients with chronic stable angina. Following ingestion of 80 ml of whisky (43% ethyl alcohol by volume) the mean heart rate and rate-pressure product decreased significantly at the end of each stage of exercise compared to corresponding prealcohol values. There were also significant derangements in systolic time intervals parameters in the form of decrease in left ventricular ejection time I and increase in pre-ejection phase I and pre-ejection phase/left ventricular ejection time ratio after alcohol intake indicating a depression in left ventricular performance. However, following alcohol intake the mean exercise time (6.5 +/- 3.8 minutes) until onset of ischaemic ST segment depression decreased significantly (P less than 0.01) compared to the corresponding prealcohol exercise time (8.6 +/- 3.5 minutes). Interestingly, the mean rate-pressure product (an indicator of myocardial oxygen demand) at the onset of ischaemic ST segment depression was significantly less (P less than 0.01) when exercise test was done after alcohol intake compared to the corresponding pre-alcohol value. The data indicated that despite significant decrease in myocardial oxygen demand produced by alcohol intake, ST T changes developed early and at a lower rate pressure product, indicating decreased blood flow to the ischaemic zones of the myocardium. This may be explained by the coronary steal effect produced by alcohol. PMID- 1761333 TI - Study of some cardiovascular parameters after chronic exposure to noise. AB - Research has focussed lately on noise as a risk factor for cardiovascular diseases. Recent findings, which have not been well confirmed, indicate that it does appear to affect heart rate, blood pressure and the electrocardiogram. This study involved two groups of subjects (with 75 and 225 in each, respectively) classified on the basis of different intensity of exposure to noise. Non occupational risk factors studied (cholesterol, blood glucose, smoking, body mass index, family history of cardiovascular problems) revealed no significant differences between the two groups. Audiometric deficits and time exposure to noise were also studied. Blood pressure was measured at rest, an electrocardiogram was taken, and a cycloergometric stress test was made. The prevalence of hypertension and electrocardiographic modifications in basal conditions and under the stress test differed to a significant extent in relation to the different exposures to noise. PMID- 1761334 TI - Clinical, psychological and thallium stress studies in patients with chest pain and normal coronary arteries. AB - The clinical and psychological profiles of 36 consecutive patients with chest pain and normal coronary arteries (study group) were compared to those of 34 patients with chest pain and significant coronary arterial disease (control group). All 70 patients were hospitalized for chest pain at least once prior to coronary angiography. The features of a typical episode of chest pain were similar in the normal coronary arteries and coronary arterial disease groups, but the female patients with normal coronary arteries had a shorter duration of a typical episode of chest pain, and the male patients with normal coronary arteries had a lower frequency of positive effort tests. Psychological testing showed the women with normal coronary arteries to have a tendency to increased somatization, anxiety, and a lower ability to identify origin of difficulties. The patients in the normal coronary and coronary arterial disease groups had psychological profiles typical of patients with chronic somatic disease. A psychiatric interview demonstrated an increased frequency of depressive trait (score 0-2) in the normal women (0.6 +/- 0.8 vs 0, P less than 0.05), and a tendency to increased somatization, anxiety, and sleeping disorders. Increased somatization was found in the normal coronary men (1.1 +/- 0.7 vs 0.5 +/- 0.7, P less than 0.05). Twenty-five patients of the normal coronary group underwent quantitative thallium stress studies, and 13 patients (52%) had evidence of stress-induced myocardial perfusion defect. There were no differences in the clinical and psychological profiles of the patients with normal and those with pathological thallium stress tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761335 TI - New onset ventricular tachycardia during pregnancy. AB - A previously healthy young woman who developed the new onset of symptomatic sustained ventricular tachycardia during pregnancy is described. Evaluation revealed mitral valve prolapse with minimal mitral regurgitation, and normal left ventricular size and function. The arrhythmia resolved after delivery, but recurred nine months later in a nonsustained form. Electrophysiologic study revealed only nonsustained ventricular tachycardia, and she was treated with propafenone. It is suggested that the pregnant state may have been important in the pathogenesis of her arrhythmia. PMID- 1761336 TI - Increased occurrence of exercise-induced silent ischemia after treatment with aspirin in patients admitted for suspected acute myocardial infarction. AB - Patients admitted for suspected acute myocardial infarction within 6 hours (mean 3 hours 42 minutes) after onset of symptoms were randomised to double-blind treatment with low-dose oral aspirin or placebo. Early exercise ischemic responses, exercise capacity and resting left ventricular ejection fraction (radionuclide ventriculography) were estimated in 77 survivors 2-4 weeks later. Exercise performance and ejection fraction in patients with confirmed acute myocardial infarction were equal in the two groups. During exercise, patients treated with aspirin had significantly more silent ischemia (ST depression without chest pain) compared to placebo (28% versus 6%; P = 0.015). The occurrence of positive exercise tests (chest pain or ST-segment depression), however, was similar in the two groups. The results indicate that the administration of aspirin early after acute myocardial infarction increases the occurrence of silent ischemia but has no effect on left ventricular function. PMID- 1761337 TI - Ventricular septal defects in a family of Yucatan miniature pigs. AB - We have studied the hearts from a colony of Yucatan miniature pigs with spontaneously occurring congenital defects. Ventricular septal defect was encountered in 57 of 81 neonates from 15 consecutive litters. Of 73 hearts preserved for morphological assessment, 52 were found to have defects within the ventricular septum remarkably similar to those observed in humans with deficient ventricular septum. The defects, including 3 which had closed spontaneously, were perimembranous in 34, muscular in 12 and doubly committed and juxtaarterial in 6 hearts. Atrial septal defects were found in 12 of the 52 hearts with deficient ventricular septation; only 1 atrial septal defect was seen among 21 hearts with an intact ventricular septum. Anomalies of the aortic arch were associated with ventricular septal defect in 2 cases; 1 with a solitary arterial trunk and one with hypoplasia of the aorta and patent arterial duct. All these findings are replicated in human hearts. This strain of pig provides an ideal large animal model for morphologic and genetic investigations concerning the details of ventricular septation, including potential mechanisms of late spontaneous closure. PMID- 1761338 TI - Noninvasive preoperative localization of an intracardiac bullet. AB - A 40-year-old patient with intracardiac gunshot injury is reported. The bullet was localized preoperatively within the pericardium at the junction of the right atrium and the inferior caval vein and was removed successfully at surgery. The role of various imaging techniques in the preoperative localization of intracardiac missiles is discussed. PMID- 1761339 TI - Successful cardiopulmonary resuscitation using high doses of epinephrine. AB - Cardiac arrest usually carries a bleak prognosis when occurring in patients who have undergone open heart surgery. We report two cases where cardiac arrest was not responsive to routine therapies. Doses of epinephrine 5-10 times higher than recommended were able to provide a resolution, and the patients were discharged in a normal neurological state. PMID- 1761340 TI - Hydatid disease of the right ventricle and role of tomographic scanning in its diagnosis. AB - A case of hydatid cyst affecting the right ventricle is described and role of tomographic scanning highlighted as it demonstrated a typical multilocular cyst arising from the right ventricle in the patient discussed here. PMID- 1761341 TI - Recurrence of an atrial myxoma. AB - A 22-year-old man had an operation 14 years ago for removal of a left atrial myxoma. He was admitted to our hospital because of acute femoral arterial embolism. Echocardiographic examination revealed a mobile pedunculated echodense atrial mass attached to the atrial septum. At operation, the left atrium was found to be occupied with a gelatinous pale mass attached by a stalk to the atrial septum. The tumour was extirpated along with a part of atrial septum, which was assumed to be involved in the tumour. The atrial septal defect created was closed with patch. Histopathological examination of excised material revealed typical features of a myxoma. PMID- 1761342 TI - Chronic atrial fibrillation and incessant ventricular tachycardia treated with a single transcatheter ablation. AB - We present a unique patient with a 12-year history of chronic atrial fibrillation resistant to external direct current shocks associated with incessant ventricular tachycardia. Both arrhythmias were treated with a single shock delivered through a catheter at the atrioventricular junction. The other unusual feature is that sinus rhythm has been maintained in a follow-up of 6 months after the intervention. PMID- 1761343 TI - Unusual electrocardiographic response during pulmonary balloon valvoplasty. AB - An 18-year-old girl with severe valvar pulmonary stenosis was subjected to balloon valvoplasty. During each inflation of the balloon, we observed transient electrocardiographic disappearance of 'R' waves in the monitoring lead. The possible explanations for this observation include sudden severe right ventricular strain and ischemia. PMID- 1761344 TI - Clinical validation of four solid state ambulatory monitoring devices in detecting shift of the ST segment. AB - Continuous monitoring for detection of changes in the ST segment during daily life in patients with stable angina has received increasing attention in recent years. Various reports testify to its role in the detection of silent ischaemia, and its potential usefulness in stratification of risk. Frequency modulated recorders, using magnetic tape for recording with subsequent visual analysis, have been previously validated for the detection of such changes. Analysis, however, is time consuming, and is subject to technical faults due to the presence of moving parts. Several new solid state devices have become available in recent years which provide real-time automated analysis, and have theoretically ideal recording capabilities with frequency response down to 0.05 Hz and linear phase integrity which may be as good, or better than, tape based recorders. We compared each of four solid state devices with a previously validated frequency modulated recording device in patients with angina in order to assess whether such devices correlate well in detecting changes in the ST segment. PMID- 1761345 TI - Double outlet left ventricle with intact ventricular septum: a cross-sectional and Doppler echocardiographic diagnosis. AB - Double outlet left ventricle with intact ventricular septum, valvar pulmonary stenosis, an atrial septal defect within the oval fossa, dysplastic tricuspid valve and normally related great arteries are described in a four-year old male child presenting with cyanosis since birth. The diagnosis was made by cross sectional and Doppler echocardiography and confirmed by cineangiocardiography. PMID- 1761346 TI - A new peptide analog (RM06) modulates the growth of hematopoietic cells. AB - The bombesin carboxy terminal dipeptide Leu-Met, was bound to hypoxanthine with a pentoxy-carbonyl chain. The new purine derivative, N-omega-[5(1,6-dihydro-6-oxo-9 purinyl)] pentoxy-carbonyl-L-leucil-L- methionine-COOH (RM06), significantly augmented human bone-marrow derived granulocyte-monocyte colony forming units (CFU-GM) when added to the cell-culture medium. Moreover, in vivo hemopoietic reconstitution was more rapid in lethally irradiated bone-marrow reconstituted BDF-1 mice, treated with RM06. Both in vitro and in vivo effects were similar to those exerted by recombinant granulocyte-monocyte colony stimulating factor (GM CSF). It is concluded that the new modified dipeptide modulates the growth of both human and murine hematopoietic cells in vitro and in vivo. PMID- 1761347 TI - Interference with oxidative processes inhibits proliferation of human peripheral blood lymphocytes and murine B-lymphocytes. AB - A number of agents capable of interfering with oxidative events were found to inhibit, in a dose-dependent manner, DNA synthesis in isolated human peripheral blood lymphocytes stimulated with phytohaemagglutinin, or phorbol myristate acetate plus ionomycin. These inhibitory substances were: the iron chelators desferrioxamine and desferrithiocin; the electron acceptor ferricyanide; the anti oxidant nordihydroguaiaretic acid; ebselen, an agent with glutathione peroxidase like activity; and diphenylene iodonium, an inhibitor of NADPH-oxidase. The actions of desferrioxamine and desferrithiocin were abolished by prior saturation with iron. Ferrocyanide was much less active in inhibiting human lymphocyte DNA synthesis than its redox partner ferricyanide. Desferrioxamine, ferricyanide and nordihydroguaiaretic acid also inhibited lipopolysaccharide-initiated DNA synthesis in mouse splenocytes in vitro. The common property of these structurally dissimilar agents is their ability to prevent formation of, or detoxify, reactive oxygen species. Thus, the data are consistent with an obligatory role for reactive oxygen formation in human T-cell and mouse B-cell activation at a stage prior to DNA synthesis. PMID- 1761348 TI - Chai-ling-tang (Japanese name: sairei-to) as an oral adjuvant. AB - Immunomodulating and anti-tumor activities of orally administered Chai-Ling-Tang (Japanese name: sairei-to, ST) were investigated. The oral administration of ST into mice augmented the antibody response to intraperitoneally administered 2, 4, 6-trinitrophenyl-haptenated sheep red blood cells (TNP-SRBC). Orally administered ST showed also an enhancing effect on the antibody response to TNP-SRBC administered by the oral route. In addition, orally administered ST markedly activated the peritoneal macrophages to enhanced phagocytic and lysosomal enzyme activities. A significant inhibition of tumor growth was observed in a syngeneic tumor-mouse system when ST was administered orally. These results suggest that ST has an efficiency as an oral adjuvant or an oral biological response modifier (BRM). PMID- 1761349 TI - Spleen cell dialyzable extracts (SCDE) mediated immunotherapy for patients with myasthenia gravis. AB - We studied 14 cases of myasthenia gravis (MG) with regard to their anti acetylcholine receptor antibody (AChR-Ab) production, peripheral blood CD4+/CD8+ ratio, and responses of peripheral lymphocytes to PHA and PWM stimulations. We found that the clinical severity was not proportional to AChR-Ab level in serum in terms of whole myasthenic population, whereas in one individual patient there was a close correlation between clinical severity and the AChR-Ab level in serum. The CD4+/CD8+ ratio in myasthenic patients was significantly higher than that of normal controls. The responses of T- and B-cells to mitogenic stimulations were impaired in myasthenic patients. The immune abnormalities found in the majority of the patients were restored to about normal after spleen cell dialyzable extracts (SCDE) therapy was applied to all patients. The results implicated that SCDE, working as an immunomodulator, could serve as a promising agent to normalize the abnormal immune functions of MG patients or other autoimmune diseases. PMID- 1761350 TI - Drug-specific F(ab')2 fragment reduces desipramine cardiotoxicity in rats. AB - Current therapy for cardiotoxicity due to tricyclic antidepressant (TCA) overdose is often ineffective in seriously poisoned patients. We studied the effect of a drug-specific antibody fragment on TCA cardiotoxicity in rats. Animals received anti-TCA F(ab')2 2.0 g/kg i.v. over 10 min starting 15 min after administration of a toxic dose of desipramine (DMI). This anti-TCA F(ab')2 dose was 36.9% of the molar DMI dose in terms of binding sites. Anti-TCA F(ab')2 infusion had no adverse effects and rapidly reduced DMI induced QRS prolongation compared with control F(ab')2 (23 +/- 14 vs 71 +/- 11% QRS prolongation at the end of infusion, P less than 0.001). This beneficial effect lasted for the 45 min duration of the study. Markedly enhanced DMI binding in serum after anti-TCA F(ab')2 was demonstrated by a 48-fold increase in the total DMI concentration over controls and a reduction in the fraction of unbound DMI (44.5 +/- 19.4 vs 0.7 +/- 0.2%). Anti-TCA F(ab')2 reduced the DMI concentration in brain but not in other organs. We conclude that anti-TCA F(ab')2 substantially reduces DMI cardiotoxicity in rats, and does so rapidly enough to be of potential clinical benefit for patients with DMI overdose. Because only a small fraction of the DMI dose was bound by antibody, these data suggest that antibody fragment doses considerably less than equimolar to the DMI dose may be effective in treating DMI cardiotoxicity. PMID- 1761351 TI - The inhibitory effect of rosmarinic acid on complement involves the C5 convertase. AB - Rosmarinic acid (RA), a naturally occurring extract from Melissa officinalis, inhibits several complement-dependent inflammatory processes and may have potential as a therapeutic agent for the control of complement activation in disease. Rosmarinic acid has been reported to have effects on both the classical pathway C3-convertase and on the cobra venom factor-induced, alternative pathway convertase. In order to define the mechanism of inhibition, the effect of RA on classical and alternative pathway lysis, C1q binding, the classical pathway convertase, the alternative pathway convertase, membrane attack pathway lysis and the generation of fragments of C3 and C5 during activation, was tested in vitro. The results showed that RA inhibited lysis by the classical pathway more than by the alternative pathway. This effect was dose-dependent with maximum inhibition of classical pathway lysis observed at 2.6 mmoles of RA. There was little effect on C1q binding or on the classical and alternative pathway convertases. However, there was highly significant inhibition of lysis of pre-formed EA43b cells by dilutions of human or rabbit serum in the presence of RA (1 mM); this was accompanied by inhibition of C5a generation. We conclude that the inhibitory effect of RA involves the C5 convertase. Such inhibition could be advantageous to the host in disorders where the terminal attack sequence plays a role in pathogenesis. PMID- 1761352 TI - Restorative effect of neurotropin on maturation of bone marrow cells to IL-2 producing T-cells in aging BALB/c mice. AB - In a previous paper, we have demonstrated that Neurotropin, a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, restores decreasing immune responses through the recovery of interleukin-2 (IL-2) production in aging BALB/c mice. To clarify the mechanism by which Neurotropin restores IL-2 production, its effect on the recruitment of IL-2-producing T-cells from bone marrow cells was examined using syngenic radiation bone marrow chimeras. Two fundamental lesions in recruiting IL-2-producing T-cells in aging BALB/c mice were demonstrated: (1) a drastic decline of the maturation of bone marrow cells to IL-2-producing T-cells as demonstrated by old----young chimeras; and (2) an environment unable to support bone marrow cell differentiation to IL-2 producing T-cells by young----old chimeras. Neurotropin clearly restored the maturation of bone marrow cells to IL-2-producing T-cells when administered from 13 to 16 month-old mice, whereas the non-complementing environment was not normalized with Neurotropin administration. These results suggest that Neurotropin administration restores IL-2 production through the recovery of the maturation of bone marrow cells to IL-2-producing T-cells, resulting in restoration of in vivo T-cell immune response in aging BALB/c mice. PMID- 1761353 TI - Differential staphylococcal protein A-induced enhancement of natural killer cell activity of lymphocytes from HIV-seropositive individuals. AB - A decrease in Natural Killer (NK) cell activity is a common feature of the immune dysfunction found in patients with HIV-induced acquired immune deficiency syndrome (AIDS). We and others have shown earlier that staphylococcal protein A (SpA) preparations enhance NK cell activity against tumor targets. The present study was aimed at exploring whether the decreased NK activity of lymphocytes from HIV seropositive subjects could be modulated or restored in vitro by SpA. Two types of HIV-seropositive subjects were studied: hemophiliac and non hemophiliac; matched controls were chosen among hospital staff and HIV seronegative hemophiliac volunteers. In vitro proliferation and interleukin-2(IL 2)/interferon gamma (IFN gamma) release in response to mitogens were also studied. NK cell responses of peripheral blood lymphocytes (PBL) of HIV seropositives were lower than those of seronegatives. However, exposure of PBL from HIV-seropositive individuals to SpA boosted their NK cell responses against NK-resistant target cells of tumor origin. The decrease in NK activity could not be attributed to the low number of NK cells, since no significant difference in NK cell number was observed between HIV-seropositive individuals and controls. Mitogen-induced blastogenic responses were present in all four groups, as was the mitogen-induced IFN gamma release. We conclude that impaired NK activity and its boosting against NK-resistant targets after SpA induction is an important characteristic of lymphocytes of HIV-seropositive individuals regardless of the disease state and that this NK defect may not be irreversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761354 TI - Activated murine natural killer cells control growth of Mycobacterium lepraemurium in mouse macrophages; in vitro and in vivo evidence. AB - The role of natural killer cells (NK) in murine leprosy was investigated in vivo and in vitro. In a first set of experiments, it was found that IL-2 (interleukin 2) activated NK cells reduced Mycobacterium lepraemurium (MLM) growth in mouse C57BL/J peritoneal macrophages which had phagocytosed low numbers (MOI of 10 : 1) of MLM (P less than 0.0001 at day 20). There was no cytotoxicity exerted by the NK cells against the infected cells in these conditions. Conversely, macrophages heavily infected with MLM (multiplicity of infection of 1000 : 1) were found to be susceptible to lysis by activated NK cells in vitro. In vivo, progressing murine leprosy was associated with a sharp increase in splenic NK cell activity, which was abrogated by treatment with a monoclonal antibody against NK cells. Administration of this monoclonal antibody against NK cells enhanced C57BL6/J mouse susceptibility to mouse leprosy, as seen by a decrease in survival time of mice infected with 10(7) MLM i.v. (81 days vs 110 days, P less than 0.0005). Overall, these findings suggest that NK cells may play an important role in resistance to leprosy, either by reducing MLM growth in macrophages or by lysing heavily infected macrophages. PMID- 1761355 TI - Cytokine modulation of Mycobacterium lepraemurium infection in mice; important involvement of tumor necrosis factor, interleukin-2 and dissociation from macrophage activation. AB - Susceptible BALB/c and resistant A/J mice were infected by the intravenous route with 10(7) Mycobacterium lepraemurium (MLM), and mortality was followed in controls and in experimental animals infused i.p. with interleukin-2 (IL-2), tumour necrosis factor alpha (TNF alpha) and interferon-gamma (IFN gamma). BALB/c mice injected with buffer and 10(7) M. lepraemurium i.v. died significantly earlier than A/J mice (111 days vs 158 days, respectively P less than 0.001), confirming earlier reports. Infusion of IFN gamma (1 or 2 micrograms every day) led to no significant increase in survival of both strains of mice infected with M. lepraemurium. Injection of IL-2 (1 microgram/day) led to a moderate increase in survival time in both strains of mice (P less than 0.01) although not changing the differences between resistant and susceptible strains of mice. Injection of tumour necrosis factor (1 microgram/day) significantly enhanced survival time in both strains (P less than 0.001), although all infected mice eventually died. The beneficial effect of IL-2 and TNF alpha on progression of the disease was seen as a modest reduction in bacterial growth in the lymph nodes and livers of BALB/c mice injected subcutaneously (approximately a one-log reduction in bacterial numbers). There was no evidence that the beneficial effect seen in vivo in mice was related to superior macrophage activation, inasmuch as peritoneal macrophages from untreated infected mice released similar amounts of superoxide anion, upon PMA triggering, as macrophages from infected and cytokine-treated mice. Moreover, macrophages from infected mice responded better to IFN gamma than cells from uninfected mice, in terms of developing tumour cytotoxicity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761356 TI - Recombinant interleukin-1 infusion increases resistance of BALB/c mice to murine leprosy. AB - BALB/c mice were infected by the subcutaneous route with 10(7) Mycobacterium lepraemurium (MLM), and the progression of the infection followed in mice injected i.p. with diluent or recombinant human recombinant interleukin-1 alpha (IL-1 alpha). It was observed that infusion of 1 microgram of IL-1 alpha per day led to a reduction of bacterial growth in the livers and popliteal lymph nodes of MLM injected mice (2-3-log reduction at 6 months, P less than 0.0001). There was no indication that IL-1 alpha infusion was acting by enhancing macrophage activation. Indeed, resident peritoneal macrophages from control infected mice were as competent as macrophages from infected mice treated with IL-1 alpha in generating superoxide anion (O2-) (approximately 400 nM O2-/h/mg at 2 months post infection). Moreover, they were no more permissive than those of IL-1 alpha infused mice for MLM in vitro as both groups of cells allowed progressive MLM growth, i.e. a 20-fold enhancement of intramacrophage MLM growth. Infusion of IL 1 alpha during MLM infection was not associated with any abrogation of the suppression of the T-cell response to T-cell mitogens or specific stimulation with antigens which is complete at 1 month post-infection. It is concluded that IL-1 alpha has immunotherapeutic potential in leprosy with the mechanism(s) of action still unclear. PMID- 1761357 TI - The effect of IFN-alpha-Con1 on hepatic cytochrome P-450 and protein synthesis and degradation in hepatic microsomes. AB - Interferon and its inducers are well known to depress drug biotransformation in the liver by decreasing the levels of cytochrome P-450 in that organ. We now report that IFN-alpha-Con1, which was constructed from the most frequently observed amino acid sequences in human alpha-interferon subtypes, causes a loss in cytochrome P-450 which could be prevented by pretreating animals with either puromycin or actinomycin D. This suggests that the loss in drug biotransformation is mediated via the production of an intermediate protein. When the turnover of microsomal protein was examined this interferon appeared to depress the synthesis of proteins with molecular weights 46-60 kd and had little effect on the synthesis of other proteins. The in vitro translation of proteins of molecular weights 45-60 kd was also depressed in an in vitro translation system using mRNA isolated from the livers of interferon treated hamsters. Interferon had no effect on the degradation of microsomal proteins of all molecular weights. It is concluded that interferon probably depresses the levels of cytochrome P-450 in the liver by decreasing the synthesis of the apoprotein and that interferon has little effect on the degradation of the hemoprotein. PMID- 1761358 TI - Suppression of demyelination by mitoxantrone. AB - The mode of action of the immunosuppressant mitoxantrone was examined in murine models of demyelinating disease. The drug has been shown to block antigen induced proliferative activity and to inhibit myelin degradation by leucocytes from paralysed mice. Mitoxantrone blocked myelin breakdown by macrophages although phagocytosis was not affected. Further evidence was obtained to indicate that mitoxantrone acts therapeutically in reducing, or at high dose, preventing signs of EAE developing in mice immunized with spinal cord homogenate and Freund's complete adjuvant. Mitoxantrone also significantly inhibited the incidence of relapse when treatment was initiated during the post-acute remission period. PMID- 1761359 TI - Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system. AB - Polysaccharides purified from large-scale cell cultures of the plant Echinacea purpurea were tested for their ability to activate human phagocytes in vitro and in vivo. These substances enhanced the spontaneous motility of PMN under soft agar and increased the ability of these cells to kill staphylococci. Monocytes were activated to secrete TNF-alpha, IL-6 and IL-1 whereas class II expression was unaffected. Intravenous application of the polysaccharides to test subjects immediately induced a fall in the number of PMN in the peripheral blood, indicating activation of adherence to endothelial cells. This fall was followed by a leukocytosis due to an increase in the number of PMN and a lesser increase of monocytes. The appearance of stab cells and some juvenile forms and even myelocytes indicated the migration of cells from the bone marrow into the peripheral blood. The acute phase C-reactive protein (CRP) was induced, probably due to activation of monocytes and macrophages to produce IL-6. In addition a moderate acceleration of the erythrocyte sedimentation rate was observed. Altogether, as in mice, the polysaccharides could induce acute phase reactions and activation of phagocytes in humans. The possibility of clinical use is discussed. PMID- 1761360 TI - Growth of murine natural killer cells from bone marrow in vitro: role of TNF alpha and IFN gamma. AB - It has been previously shown that natural killer (NK) cell growth can be induced by interleukin-2 (IL-2) in bone marrow (BM) cultures and that other cytokines (CKs), including IL-1 alpha, act synergistically with IL-2. However, as the effect of IL-2 and IL-1 alpha could be due to direct stimulation of NK progenitor cell growth, as well as to the induction of other factors, we analysed the role of the endogenous production of CKs in BM cultures. Results show that mRNAs specific for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) are detectable within hours in BM cultures supplemented with IL-2 and IL-1 alpha, and that the amount is higher when both IL-2 and IL-1 alpha are present. Antibodies directed against TNF alpha and IFN gamma abrogate the NK cell development, indicating that these CKs play an essential role. The antibodies, however, had no effect on mature NK cells. Furthermore, pretreatment of BM cells with TNF alpha or IFN gamma before culturing with IL-2, enhances IL-2 responsiveness and NK cell growth. These results suggest that induction of cytokines production may be important for growth of NK cells from BM precursors and that the synergistic effect of IL-1 alpha could be due, at least in part, to increased TNF alpha and IFN gamma production. PMID- 1761361 TI - Modulation of circulating colony-stimulating activity in mice: combined effects of IL-1 and bacterial or indomethacin treatment. AB - We have investigated the effects of interleukin 1 (IL-1) administration on circulating levels of colony-stimulating activity (CSA) in intact or neutropenic mice. Intact or cyclophosphamide-treated mice received human rIL-1 beta according to different regimens, and their sera were assayed for CSA at 4, 24 or 48 h. The results indicated that (1) cyclophosphamide alone significantly increased the level of circulating CSA, (2) administration of IL-1 to intact or neutropenic mice resulted in a biphasic pattern of CSA response, an early burst at 4 h being followed at 24-48 h by a significant decrease. In nongranulocytopenic mice, the combined treatment with IL-1 and bacterial cells also resulted in a biphasic pattern of CSA response. However, when IL-1 was administered in concurrence with the cyclo-oxygenase inhibitor indomethacin, sustained CSA levels could be observed for a prolonged period of time. These data expand upon our previous observations on modulation of CSA by IL-1 in granulocytopenic mice, and further support the concept that IL-1 may have both positive and negative effects on the expression of circulating CSA. PMID- 1761362 TI - Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B. AB - To examine whether sizofiran (SPG), a polysaccharide isolated from Schizophyllum commune Fries, could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV) nucleocapsid antigens, we investigated in vitro the production of interferon-gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe), and proliferation by peripheral blood mononuclear cells (PBMC) from six patients with chronic hepatitis B and four control individuals in the presence of recombinant HBcAg and purified HBeAg. Sizofiran alone in culture and in combination with HBV Ag was found to enhance IFN-gamma production and the proliferative response of PBMC from the patients compared with corresponding medium or HBV Ag alone culture. In contrast, antibody production was not elicited by SPG alone, but amplified by the drug in HBcAg stimulated culture. In vitro leukocyte IFN-alpha addition increased IFN-gamma production, but suppressed the proliferation of PBMC from both controls and patients in the presence or absence of SPG and HBV Ag. These results indicate that SPG is able to modulate both cellular and humoral immune responses specific for nucleocapsid antigens in patients with chronic hepatitis B. PMID- 1761363 TI - Host resistance to murine malaria in mice exposed to the adenosine deaminase inhibitor, 2'-deoxycoformycin. AB - Resistance to infection with the nonlethal rodent malaria parasite Plasmodium yoelii 17XNL (Py 17XNL) is mediated by humoral, T-cell and accessory cell activity. The purpose this study was to profile host resistance to infection with this organism in mice exposed to 2'-deoxycoformycin (2dCF), a potent adenosine deaminase (ADA) inhibitor. Inhibition of ADA activity by 2dFC results in defective T-cell function and either suppression or augmentation of the humoral response, depending on whether 2dCF exposure precedes (suppression) or follows (augmentation) immunization. In this study, mice injected with 2dCF during the first five days of infection cleared the infection at the same time as controls, but had lower peak parasitemia than controls. Mice infected with the lethal variant of P. yoelii were more susceptible to infection when injected with 2dCF after infection, suggesting that 2dCF injection did not directly affect the parasite. Rather, suppression of parasitemia in 2dCF-treated mice may have been mediated by augmented humoral immunity, since 2dCF injection increases antibody responses when 2dCF injection follows antigen (in this case, parasite) injection. Conversely, in mice given 2dCF prior to infection, parasitemia peaked 2 days later and was eliminated more gradually than in control mice. Exposure to 2dCF did not deplete reticulocytes and thus temporarily limit parasitemia. Similarly, enrichment of NK cells or augmentation of macrophage phagocytic activity prior to infection were not sufficient to alter the pattern of infection. In contrast, the pattern of infection in mice treated with tilorone (a macrophage activator which also causes suppressed T-cell function) prior to infection was similar to that observed in 2dCF-exposed animals. These results indicate that 2dCF, given before or after infection, alters the host response to infection with Py17XNL. It appears that a combination of increased macrophage activity and altered T-cell activity contributed to the delay in peak parasitemia and clearance of infection in mice exposed to 2dCF before infection with Py17XNL. PMID- 1761364 TI - Clinical benefits and recovery of delayed-type hypersensitivity in patients with AIDS-related complex treated with IMREG-1 or placebo. AB - IMREG-1, an immunomodulatory biological therapeutic, was studied in a placebo controlled, double-blind, six-month trial in 45 anergic patients with AIDS related complex (ARC) and 4 with Kaposi's sarcoma, which was followed by compassionate IMREG-1 administration to all subjects. The IMREG-1 group had significantly less AIDS-defining events compared with the placebo group during the randomized trial (6.9 events per 100 person-years vs 43.7 events per 100 person-years, P = 0.018, relative risk 6.33) and the total observation period. Patients receiving IMREG-1 significantly improved their work performance. Nine (41%) of 22 patients in the IMREG-1 group, compared with one (14%) of seven in the placebo group, recovered cutaneous reactivity to tetanus toxoid. At the end of the six-month trial, CD4+ counts were 0.429 x 10(9)/l in the IMREG-1 group and 0.304 x 10(9)/l in the placebo group (P = 0.04). IMREG-1 is a promising therapeutic for HIV-infected patients with symptoms of ARC. PMID- 1761365 TI - Primary structure of alpaca growth hormone. AB - Reduced and carbamidomethylated alpaca growth hormone was submitted to tryptic digestion. Peptides in the mixture were purified by reverse phase HPLC and N terminal determination and an amino acid analysis of each was performed. Data obtained and the already known primary structure of the equine growth hormone allowed the assembly-by homology-of a definite sequence of amino acids for the polypeptide chain of the protein. Present data provide further information about the relationship between growth factors. PMID- 1761366 TI - Vibrational circular dichroism spectra of unblocked proline oligomers. AB - Vibrational Circular Dichroism (VCD) spectra of unblocked L-proline oligopeptides, (Pro)n n = 3 to 7, dissolved in D2O are reported. For these oligomers, the VCD spectra can be attributed to a conformational dominance of the trans amide conformation with subunits interrelated by a left-handed twist, particularly for the longer oligomers. As a function of oligomer length, formation of this conformation starts at n = 3; and by n = 5 a spectrum closely resembling that of the poly-L-proline II helix in shape and magnitude is seen. The VCD data are compared with previous (Pro)n results using IR, CD, Raman and NMR spectroscopies, and reasons for the variations in interpretation are discussed. PMID- 1761367 TI - Mapping the receptor-recognition site of human transforming growth factor-alpha. AB - The receptor-recognition site human transforming growth factor-alpha (TGF alpha), a 50-residue tricyclic peptide with three disulfide bonds, was mapped by a set of 46 peptide analogs consisting of linear, monocyclic, bicyclic, and tricyclic structures representing individual and overlapping subdomains of human TGF alpha. Linear overlapping fragments ranging from 7 to 18 residues and spanning the entire length of TGF alpha as well as monocyclic analogs with one disulfide linkage were found to be inactive in both receptor-binding and mitogenic assays. Bicyclic analogs with two disulfide linkage and representing either the amino or carboxyl two-thirds of TGF alpha showed low activity at 0.1-0.9 mM concentrations. Tricyclic analogs containing all three disulfide linkages but lacking either the amino or carboxyl terminal heptapeptide was, respectively, 3% and 0.1% as active as TGF alpha. These results show that determinants for the receptor binding cannot be represented by a short continuous fragment or a single subdomain, but are located on a discontinuous surface on a folded structure with disulfide restraints. Furthermore, these results when combined with our previous results which shows that the middle subdomain (second disulfide loop) is not involved in the receptor binding suggest that the receptor-binding residues are constituted of three fragments located at the first and third subdomains as well as the external carboxyl peptide. PMID- 1761368 TI - Molecular properties of poly(RGD) and its binding capacities to metastatic melanoma cells. AB - We examined the binding capacity of anti-metastatic polypeptide containing repetitive Arg-Gly-Asp(RGD) sequence derived from cell binding site of fibronectin, poly(RGD), to the surface of tumor cells. Poly(RGD) competitively inhibited the binding of radiolabeled fibronectin to the cell surface more potently than oligo(RGD) or RGD tripeptide on a molar basis. Compared on a weight basis to oligo(RGD) or RGD peptide, poly(RGD) was more active than the oligo- and monomeric peptide at inhibiting tumor cell adhesion to immobilized fibronectin. The secondary structure of poly(RGD) was predicted to be a beta-turn from the data of CD spectra and its amino acid sequence. These findings suggest that poly(RGD)-mediated inhibition of cell adhesion is due to its potent binding capacity to fibronectin receptors on cell surface probably through its conformational properties. PMID- 1761369 TI - Stabilities of leucine zipper dimers estimated by an empirical free energy method. AB - The leucine zipper motif is a characteristic amino acid sequence found in dimeric DNA-binding proteins. Computer-generated models for leucine zippers were constructed as alpha-helical coiled dimers with leucine repeated every seventh residue. An empirical Gibbs free energy, delta G, function which incorporates hydrophobic force, electrostatic interactions, and conformational entropy loss as the major intermolecular interactions was used to estimate the delta G of dimer formation in fos, jun, and GCN4 zipper sequences. The calculations showed that complexes known to form stable homo- or heterodimers have favorable (negative) delta G, while other less stable complexes have unfavorable (positive) delta G. Leucines in position d of the coiled coil contribute large hydrophobic stabilization energies while residues in the a position contribute less to dimer stability. Hydrophobic contributions show little sequence specificity, however, and do not contribute significantly to homo/heterodimer preference. Charged residues in the e and g positions, on the other hand, determine homo/heterodimer specificity. In GCN4 homodimers, residues GLU el, Glu b2, Lys g2, and Lys e4 greatly contribute to dimer stability. The preferential stability of fos-jun heterodimer over the jun-jun and fos-fos homodimers is primarily due to the side chains Asp b1, Glu g1, Asp b2, Glu e2, Glu g2, Glu g3, and Lys a5 of the fos helix, and Arg c1, Lys g1, Lys b2, Lys e2, Arg e4, and Glu g4 of the jun helix. PMID- 1761370 TI - Stereocontrolled synthesis of psi[CH = CH] dipeptide isosteres. AB - A new stereocontrolled synthesis of the psi[CH = CH] dipeptide isostere is described. They key step of the sequence relies on the stereospecific alpha alkylation of delta-amino-gamma-mesyloxy-alpha,beta-unsaturated esters. The broad availability of nucleophilic alpha-side chains by this method allows the preparation of a wide variety of psi[CH = CH] isosteres with predictable stereochemistry. PMID- 1761371 TI - Peptides from chiral C alpha,alpha-disubstituted glycines. Synthesis and characterization, conformational energy computations and solution conformational analysis of C alpha-methyl, C alpha-isopropylglycine [(alpha Me)Val] derivatives and model peptides. AB - Conformational energy computations on Ac-L-(alpha Me)Val-NHMe indicate that turns and right-handed helical structures are particularly stable conformations for this chiral C alpha-methyl, C alpha-alkylglycyl residue. We have synthesized and characterized a variety of L-(alpha Me)Val derivatives and peptides (to the pentamer level). The results of the solution conformational analysis, performed using infrared absorption, 1H nuclear magnetic resonance, and circular dichroism, are in general agreement with those obtained from the theoretical investigation, in the sense that the L-(alpha Me)Val residue turns out to be a strong beta-turn and right-handed helix former. A comparison is also made with the conclusions extracted from published work on peptides rich in other C alpha-methyl, C alpha alkylglycyl residues. PMID- 1761372 TI - Circular dichroic and 1H-NMR studies on the aged form of bovine plasma albumin. AB - Bovine plasma albumin (BPA) has 17 disulfide bonds and approximately one SH group at Cys-34 which catalyzes the intramolecular SH, S-S exchange reaction in the alkaline region at low ionic strength, resulting in the formation of the aged form (A-form). 1) Fractions of alpha-helix (f alpha) and beta-form (f beta) of iodoacetamide-blocked non-aged BPA (IA-BPA) at pH 6.5 (the N-form) and 9.0 (the B form) in the absence of added salt were 0.70, 0.12 and 0.62, 0.18, respectively (Era et al. (1990]. However, there were no changes in f alpha and f beta of the iodoacetamide-blocked A-form (IA-A-form) over the pH range from 5.5 to 9.1 in the absence of added salt or in 0.10 M KCl (f alpha approximately 0.60, f beta approximately 0.20), indicating that the secondary structure of the IA-A-form might be similar to that of non-aged IA-BPA at pH 9.0 (B-form) in the absence of added salt, that is, the frozen B-form, stabilized covalently by the repairing of disulfide bonds. 2) The rigidity of the A- and IA-A-forms, as monitored by cross relaxation times between irradiated and observed protein protons, was similar to or slightly higher than that of non-aged IA-BPA or BMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761374 TI - 4-Alkyl-5(4H)-oxazolones from mixed anhydrides of N-formylamino acids. PMID- 1761373 TI - Enzymatic peptide synthesis in organic solvent mediated by gels of copolymerized acrylic derivatives of alpha-chymotrypsin and polyoxyethylene. AB - Copolymers of acrylated derivatives of alpha-chymotrypsin and polyethylene glycol (PEG) have been prepared and used as biocatalysts for the synthesis of model peptides in organic solvent containing a low quantity of water. Other peptide couplings have been tried to point out the chemico- and stereoselectivity and examples of segment couplings are given. PMID- 1761375 TI - Outcomes of nursing care: the case of primary nursing. AB - Using primary nursing as a 'case study', this paper reviews research literature which attempts to measure the effectiveness of a mode of nursing using outcome measures. Previous research, it is argued, is hampered by a lack of conceptualization of structure and process and inadequate research design, with consequent uncertain findings. A shift in emphasis is suggested from an evaluation of global concepts, such as primary nursing, to an identification of the features of structures and processes of nursing care which interrelate with patient and nurse outcomes. For this purpose, multivariate research design and investment in methodological research are recommended. PMID- 1761376 TI - From san gu liu po to 'caring scholar': the Chinese nurse in perspective. AB - This study presents a re-evaluation of the origins of Chinese nursing from the earliest traditional carers to the mature, professionalized institution of the republican period. The influence of traditional cultural values on the nature of the modern profession is discussed and its emergence considered in historical context with particular attention to the role of missionaries, philanthropic institutions and other aspects of foreign intervention, both European and Japanese. The Chinese anti-imperialist response, as stimulated by the 'May 4th Movement' and later the Sino-Japanese war, is shown to be an important ingredient in the transition from foreign to national control of the profession and in its achieving respect. Some doubt is cast on the assumption that Chinese nursing has followed a process of rapid convergence to the Western model. PMID- 1761377 TI - The introduction of a new system of care delivery into a surgical ward in Sweden. AB - Action research is used to implement a change in the system of care delivery on a surgical ward in Sweden. Couched within a Lewinian framework the stages of change, the problems faced by staff and their solutions are described. The effects of the change to a system of care more closely resembling the Loeb model of primary nursing, in which accountability is for the duration of the shift, were closely monitored. Observation of registered nurses showed a three-fold increase in the time spent giving direct patient care. A significant increase in scores on a measure of "Intrinsic Job Satisfaction" was also found (P less than 0.01) together with increased scores on a measure of "Patient Focus" (P less than 0.001). These findings were sustained over time. The problems of evaluating a system of care which is based on a different philosophy are addressed. PMID- 1761378 TI - Patient satisfaction with nursing care in Alexandria, Egypt. AB - The study assessed the satisfaction of medical and surgical patients in a university hospital in Egypt using the La Monica/Oberst Patient Satisfaction Scale. In spite of the nursing shortage in that hospital, the results indicated that patient satisfaction was high. The implications for nursing care are discussed in terms of the validity of the scale and the objectivity of clients when responding to the questionnaire. PMID- 1761379 TI - The oral complications of specific anticancer therapy. AB - Oral complications commonly affect cancer patients undergoing active treatment. These include oral infection, gingival bleeding, stomatitis/mucositis, xerostomia, dental caries and periodontal disease. The oral cavity also acts as an entry site for systemic infection, particularly in those who are myelosuppressed. This paper reviews the structure and function of the oral cavity and how this may be affected by anticancer therapy. Oral care procedures are discussed and controversial areas highlighted showing that, although it is generally agreed that oral care is essential in preventing/minimizing complications and maintaining general comfort, there is no general agreement about the frequency with which care is required or about the tools and agents to be employed. Areas for future research are highlighted. PMID- 1761380 TI - Nurses' smoking worldwide. A review of 73 surveys on nurses' tobacco consumption in 21 countries in the period 1959-1988. AB - Nurses are the largest professional group in health care. Nurses' smoking is not only important to their personal health, but also to the public's health. Analysis of smoking prevalences found among nurses in 21 countries in the period 1959-1988 shows that considerable numbers of both female and male nurses are smokers. More often than not there are found as many smokers among nurses as among the general population, sometimes even more. Only in Canada and Finland female nurses smoked clearly less than the population at large. Nurses' smoking prevalences decreased slowly in industrialized countries. An exemplary role is recognized by many nurses; more so by non-smoking nurses than by their smoking colleagues. Factors influencing nurses' smoking are professional socialization, duality of roles, workstress, discrepant expectancies about nurses' role and lack of social support. Theoretical explanations for nurses smoking by means of the theories of strain, of selection, of social control and of professional subculture are discussed. Future research should be internationally coordinated and aimed at comparability within a cultural and organizational context. PMID- 1761381 TI - Social support, participation and collaboration of relatives in domiciliary care. AB - This article is based on material from two domiciliary care studies which were carried out in two large towns in southern Finland. The patients in domiciliary care received a considerable amount of both practical and mental or social support from their relatives. Support received from relatives correlated with patients' well-being. Patients who had more difficulties with physical daily activities received more help from relatives than patients who had less difficulties. Therefore, the help from relatives was necessary for continuing home care, especially for those whose physical condition was poor. The participation of relatives in the patient's care, particularly when they were able to collaborate with domiciliary care providers, improved the quality of patient care and enhanced the security and satisfaction of the patient. PMID- 1761382 TI - On applying psychoanalytic explanation in phenomenological research. AB - In this paper I propose to examine the theoretical underpinnings of phenomenological research which is plagued with the same methodological problems that confronted psychoanalysis at the turn of the century. Some general criticisms levelled at both phenomenological and psychoanalytic research, by philosophers of science, point to: the absence of falsifiable hypotheses; the absence of measurable and observable data; and the absence of an explanatory general theory upon which the study of consciousness may be grounded. The primary task of the present analysis is to articulate the structural similarities that obtain between psychoanalysis and phenomenology in the expectation that the rules of evidence governing psychoanalytic research may also apply in the government of phenomenological research. Finally, I shall offer some procedural suggestions phenomenologists might care to consider. PMID- 1761383 TI - Calcium transport across epithelia. PMID- 1761384 TI - The Golgi apparatus and membrane trafficking in green algae. PMID- 1761385 TI - Cellular and molecular biology of Pneumocystis carinii. PMID- 1761386 TI - [Chronic pancreatitis]. PMID- 1761387 TI - [Pathophysiology and practical diagnostic importance of the IgE system for allergies]. PMID- 1761388 TI - [Epidemiology of allergic diseases]. PMID- 1761389 TI - [Food allergy]. PMID- 1761390 TI - [Occupationally-induced respiratory allergies of the immediate type]. PMID- 1761391 TI - [Allergologic diagnosis of drug hypersensitivity reactions]. PMID- 1761392 TI - [The environment and allergen expression]. PMID- 1761393 TI - [Hyposensitization]. PMID- 1761394 TI - [46-year-old patient with congenital actinic dermatosis and progressive liver failure after travel to Southeast Asia]. PMID- 1761395 TI - [Comment on the contribution by K. Rieke, M. Spranger and W. Hacke: Ischemic stroke (focal cerebral ischemia)]. PMID- 1761396 TI - [Circulatory disorders in the area of the internal carotid artery]. PMID- 1761397 TI - [Do increased serum bile acids induce pruritus?]. PMID- 1761398 TI - Human mononuclear cell chemiluminescence and interleukin-1 release induced by Staphylococcus aureus protein A. AB - Staphylococcus aureus protein A (SpA) is shown to induce a temporary chemiluminescence (CL)-response of human peripheral blood mononuclear cells. Maximal activity of SpA is observed at 3 micrograms/ml and EC50 is about 1 microgram/ml. The CL response depends on extracellular calcium, and moreover is inhibited by pretreating cells with rabbit-anti-human IgG's. From glass-adhered monocytes, SpA alone (3 micrograms/ml) did not consistently affect the generation of immunoreactive interleukin-1 (IL-1). However, SpA and endotoxin (1 micrograms/ml) showed a marked synergistic effect on IL-1 release. The results suggest that SpA interacts with membrane-bound Ig molecules endowed with receptor functions. The CL response may be envisaged as a result of early transmembrane signalling events presumably taking place in monocytes. Apparently, hereby, the cells become primed for endotoxin-triggered IL-1 release. PMID- 1761399 TI - Epithelial modulation of thromboxane A2 and PAF involvement in IgE- and IgG mediated guinea pig anaphylaxis. AB - The role of prostanoids and platelet-activating factor (PAF) was studied in the in vitro response of guinea pig trachea to immunochallenge according to the presence or the absence of the epithelial layer and to the sensitization procedure leading to the preferential synthesis of immunoglobulin E (IgE) or immunoglobulin G (IgG) antibodies. Indomethacin, a cyclooxygenase inhibitor, potentiated the antigen-induced contractions both in IgE and IgG models, suggesting the involvement of relaxant prostaglandins (PGs), independently of the presence of the airway epithelium. UK-38485, a thromboxane synthetase inhibitor, did not modify the tracheal response to antigen in the IgE model. However, this compound enhanced the maximum contractile response to antigen of the intact tracheal strips of IgG-sensitized guinea pig, but reduced the contractile response of the epithelium-free tracheal strips. Two potent non-structurally related PAF antagonists, Ro 19-3704 and BN 52021, reduced antigen-induced contraction of the epithelium-free tracheal strips in the IgE model. In contrast, these compounds did not affect the contractile responses of the preparations in the IgG model. These results suggest the selective implication of thromboxane A2 and PAF, in IgG- and IgE-mediated guinea pig anaphylaxis respectively. Finally, these results indicate that thromboxane A2 (TXA2) and PAF are potent inducers of epithelium-derived mediators. PMID- 1761400 TI - Resistance of C57Bl/6 mice to immunosuppressive effects of aflatoxin B1 and relationship with neuroendocrine mechanisms. AB - Aflatoxin B1 (AFB1) a secondary metabolite of Aspergillus flavus and A. parasiticus, is known for its carcinogenicity and immunosuppressive effects. We previously reported on the immunosuppressive effects of AFB1 in Swiss and CD-1 mice. This study concerned the involvement of the hypothalamus-pituitary-adrenal gland axis in the immunosuppressive effects of AFB1 in C57Bl/6 mice. Animals were treated orally with 30, 150 or 750 micrograms/kg AFB1 daily for four weeks. Splenic lymphocytes were assayed to investigate their phenotyping using flow cytometry, proliferative response against mitogens and allogeneic lymphocytes, cytolytic cell activity, and IL-2 production. Antibody-mediated immunocompetence was checked using sheep red blood cell (SRBC)-challenged animals by plaque forming cell assay and enzyme-linked immunosorbent assay. The dose of AFB1 for the immunosuppressive effects on blastogenic response, IL-2 production, and primary antibody production of splenic cells was much higher than previous studies involving other mice strains. AFB1 decreased the amount of circulating anti-SRBC antibody, and the helper-T cell and B cell populations in phenotyping splenic lymphocytes. There were no significant changes in natural killer cell activity, mixed lymphocyte response, hypothalamic biogenic amine concentrations, and corticotropin releasing factor, and of adrenocorticotropic hormone and corticosterone in plasma. Results were confirmed using adrenalectomized mice. The hypothalamic-pituitary-adrenal axis does not appear to have a major role in AFB1 induced immunotoxicity. PMID- 1761401 TI - Immunomodulation by 9-amino-1,2,3,4-tetrahydroacridine (THA): 1. Down-regulation of natural cell-mediated cytotoxicity in vitro. AB - THA (Tacrine), a drug used in the experimental therapy of dementia of Alzheimer's disease type, and whose biochemical site of action is believed to be the neural cholinesterase, is shown, for the first time, to be an immunosuppressant in vitro on normal human peripheral blood lymphocytes in microgram quantities. THA down regulates non-MHC restricted natural killer (NK) cell activity without affecting the general viability of cells. This down-regulation can be demonstrated at all effector and target (K562) concentrations, in purified resting NK cells as well as in lymphokine (interleukin 2) activated killer cells in 3- or 16-h NK assays and in all the blood samples tested. Kinetic analysis shows that the Vmax (maximal cytotoxic potential) and Km of NK cell-mediated cytolysis are also attenuated. Single cell assays using agarose matrix reveal that THA moderately interferes with tumor target binding/recognition events and strongly abrogates the delivery of lethal hit, thus lowering the frequency of active killer cells among THA-treated lymphocytes. THA down-regulates NK cells upon direct interaction and does not require the help of non-NK cells. The THA sensitive site(s) on NK cells does not appear to be perturbed significantly either by their proliferative status or by membrane modulations that may be normally induced by interleukin 2. The in vitro immunomodulatory pharmacological properties of THA reveal that the biological site of action of THA extends to non-neural cells also. Such non-neural models may be helpful in exploring the pathophysiological neuroimmunomodulatory properties of THA at cellular and molecular levels. PMID- 1761402 TI - Ganglioside (GM1)-treated T cells shed CD4. AB - In previous studies (Morrison et al., 1990), we showed that ganglioside (GM1) modulation of CD4 was associated with activation of phospholipase C and increased production of inositol triphosphate, but not with activation of protein kinase C. These results demonstrated a unique signal transduction pathway related to GM1 modulation of CD4 on T cells and raised the question as to whether intracellular Ca2+ levels and related protein kinases would be affected by GM1-induced signalling. We now show that GM1 modulation of CD4 from human T cells corresponds to decreased cellular Ca2+ without significant changes in cellular protein phosphorylation. In the course of this study we discovered that T cells challenged with GM1 exhibited new proteins in their surrounding media. Fractionation of cellular and supernatant proteins show that cells treated with GM1 released proteins with an approximate molecular weight (Mr) of 49,000. This was exclusive of GM1 protein association and GM1-induced protein phosphorylation. Immunoblots demonstrated the presence of CD4 in GM1-treated cell supernatants. Western immunoblots using anti-CD4 antibodies detected a lower Mr form (49,000) of CD4 in the supernatants of GM1-treated cells. These studies further define the unique nature of GM1 signalling relating to modulation of CD4 and demonstrate that the fate of GM1 modulated CD4, in part, involves protein shedding. PMID- 1761403 TI - Does verapamil act as an immunomodulatory drug in vivo? AB - Based on in vitro data, previous investigators have hypothesized that Ca2+ entry blockers might affect lymphocyte activation, proliferation and effector function. We have tested this hypothesis by comparing the in vitro and in vivo effects of the Ca2+ entry blocker verapamil on human lymphocytes. In vitro high concentrations of verapamil (100 microM) inhibited mitogen-stimulated Ca2+ influx, inositol phosphate generation, and proliferation; similar effects were observed with diltiazem and nifedipine. In vivo treatment of healthy volunteers with verapamil (2-4 times 240 mg per day for 7 days) did not affect the number of circulating lymphocytes or their subset distribution. Moreover, we did not observe any effect of in vivo treatment with verapamil on mitogen-stimulated lymphocyte proliferation or expression of interleukin-2 receptors in vitro. We conclude that the inhibitory effects of verapamil on lymphocyte activation in vitro are unlikely to be of therapeutic relevance and may not be related to the Ca2+ entry blocking effects of this drug. PMID- 1761404 TI - Pathogenesis of limb malformations in mice induced by methoxyacetic acid. AB - The present study was performed to reveal the pathogenesis of limb malformations induced by methoxyacetic acid (MAA) in developing mouse limbs. Pregnant Jcl:ICR mice were orally given at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Various patterns of cell death in limb buds were observed by vital dye staining with Nile blue A. Under a light microscope and transmission electron microscope, excessive cell death was observed in the mesenchyme as well as in the apical ectodermal ridge (AER) 2 hr after MAA treatment, reaching a maximum after 6 hr. Scanning electron microscopic examinations showed hypoplasia of the AER and small hand plates 24 hr after treatment. Small hand plates and delayed digital ray formation were noted at 48 hr. Neither detachment nor massive necrosis was detected in the periderm covering the limb bud. The distribution of cell death 6 hr after treatment was similar in limb buds treated either at gd 10.5, 11.0 or 11.5, but the final pattern of limb defects was different in fetuses treated at different stages. This study indicates that variations in the pattern of limb defects induced by MAA are due to differences in the amount and distribution of cell death, together with differences in the regenerative capacity of surviving cells. PMID- 1761405 TI - Transantral ligation of the maxillary artery for refractory epistaxis. A case report. AB - A case of severe arterial epistaxis treated by transantral ligation of the maxillary artery is reported. A 66-year-old woman had recurrent left sided epistaxis from the posterior nasal cavity which was difficult to control by conventional nasal packing methods. Selective angiography was performed to identify the arterial flow patterns and site of bleeding which was confirmed to be the descending palatine artery. Following radiographical examination, ligation and clipping of the maxillary artery and its branches was performed with transantral approach under general anesthesia. No further epistaxis occurred after the ligation. This surgical procedure seems to be relatively simple and highly effective in the management of refractory epistaxis. PMID- 1761406 TI - Intracavitary drainage procedure for giant bullae in compromised patients. AB - Two cases of giant bullae were treated by intracavitary suction and drainage procedure under local anesthesia because of the poor pulmonary function. After staged bullectomy, the patients returned to normal life. The first case was admitted to our intensive care unit (ICU). Tube drainage was performed in the giant bulla of the left lung immediately after admission. One month after recovery from right heart failure and mediastinal shift to the right side, bullectomy was performed using linear stapler. The patient was discharged 20 days later. The second case was admitted with severe dyspnea and bilateral giant bullae were noticed. We performed tube drainage for larger bulla of the left lung under local anesthesia. Two months later, bullectomy was performed on the right side, because the bulla on the left side became smaller and the general condition of the patient improved. The patient was discharged three months later on foot and has since been asymptomatic. Giant bulla is a well-established clinical entity which includes abnormal dilatation of various parts of the tracheo bronchial tree and other discrete sacs originating from the interstitial portion of the lung. Giant bullae are frequently associated with marked dyspnea and emphysematous symptoms. However, these symptoms depend upon various factors: size, location, valvular mechanism, condition of the contiguous lung parenchyma and the changes that may take place in the intrathoracic pressure. PMID- 1761407 TI - Pattern of limb malformations in mice induced by methoxyacetic acid. AB - The present study investigated the pattern of limb malformations induced in mice by methoxyacetic acid (MAA), one of di(2-methoxyethyl) phthalate (DMEP) metabolites. Pregnant Jcl:ICR mice were given orally at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Fetuses were examined at gd 15.5 for external and skeletal malformations. Limb defects were maximum in frequency and severity after administration at gd 11.5. Forelimbs had greater susceptibility than hindlimbs. Treatment at gd 10.5 produced cutaneous or osseous syndactyly between digits I and II, II and III, and ectrodactyly of digit II or digit I. Intercalary defects in the forelimbs were also detected. No hindlimb malformations were induced. Treatment at gd 11.0 induced ectrodactyly of digit II and digit I in the forelimbs, as well as osseous syndactyly or intercalary defects of the metacarpals or phalanges, and the frequency became increased. Hindlimb malformations were also detected in a small number with syndactyly between digits I and II or ectrodactyly in digit I. Treatment at gd 11.5 induced ectrodactyly in the forelimbs. Half of the forelimbs showed ectrodactyly with four missing digits (digits I, II, III, and V) and the remaining limbs showed ectrodactyly with a similar frequency with one, two, or three missing digits, either in the pre- or postaxial area. In the hindlimbs ectrodactyly with one, two, or three missing digits was the most common malformation observed. Syndactyly between digits I and II was also induced in a small percentage. PMID- 1761408 TI - Credentialing by legislative fiat: implications for the allied health professions. PMID- 1761409 TI - Legalistic ethics and the lingering doubt about withdrawing life-supports. PMID- 1761410 TI - Influencers of career choice among allied health students. AB - This study focused on the factors that influence students' choice of an allied health profession. A survey of 153 students in three allied health programs at the University of Connecticut revealed that "the need to help others," "prestige," "professional autonomy," "opportunities for advancement," "income potential," and "the effect of the specialty on family and personal life," were the major influencers of career choice among allied health students. Only a few students regarded malpractice suits and AIDS as negative influencers. While medical laboratory science majors regarded these as important factors, dietetics and physical therapy majors did not. The article suggests further use of these findings by program directors and career counselors. PMID- 1761411 TI - An evaluation of AIDS education: a quasi-experimental exploration. AB - This study reports on a quasi-experimental study designed to evaluate the relationship between receiving classroom instruction and subsequent AIDS knowledge, behavior, and attitudes. Survey information was gathered from 61 students enrolled in an AIDS course and 68 students enrolled in "control" courses. Both groups were pretested at the beginning of the semester and again at the end of the semester concerning AIDS knowledge, behavior, and attitudes. The results obtained indicated that there was a widespread acceptance of the conventional wisdom concerning AIDS in both the experimental and control groups prior to the study. Few behavior changes were observed as a result of the AIDS curriculum. Three empirically distinct factors, "interaction," "constraint," and "testing," emerged from the attitude measures. Respondents were more accepting of interacting with persons with AIDS across time. Moreover, respondents in the experimental group were more reticent to advocate mandatory AIDS testing vis-a vis those in the control group across time. PMID- 1761412 TI - An analysis of revised federal budget procedures. PMID- 1761413 TI - Advances in health informatics and implications for allied health education. PMID- 1761414 TI - Studies on the isotetracenone antibiotics. IV. Hatomarubigins A, B, C and D, new isotetracenone antibiotics effective against multidrug-resistant tumor cells. AB - A complex of new isotetracenone group antibiotics was isolated from the cultured broth of Streptomyces sp. 2238-SVT4. It consisted of four related compounds, designated hatomarubigins A, B, C and D, whose structures were elucidated by NMR spectral analysis including a variety of 2D techniques. They enhanced the cytotoxicity of colchicine against multidrug-resistant tumor cells. PMID- 1761415 TI - Structures of aureobasidins B to R. AB - Structures of 17 minor forms of aureobasidins (Abs), Abs B-R, were elucidated by mass fragmentation and amino acid analysis. The fragmentation patterns by FAB-MS spectroscopy of Abs A-E seemed to follow predictable rules, so we used the rules to elucidate the 13 other Abs. All Abs consisted of eight amino acids and one hydroxy acid. PMID- 1761416 TI - NMR studies of aureobasidins A and E. AB - The 1H and 13C NMR spectra of aureobasidins A and E were analyzed by a variety of 2D NMR techniques. Two isomers of aureobasidin A existed as an equilibrium mixture in deuteriochloroform. The isomerism was associated with cis-trans rotation of the amide bond between N-methylphenylalanine and proline. Almost all of the aureobasidin E was found in deuteriochloroform as one conformer; the amide bond between beta-hydroxy-N-methylphenylalanine and proline was in the cis conformation. Experiments with the NOE made identification of the conformation of the amide bonds of aureobasidins A and E possible. PMID- 1761417 TI - An NMR study of eremomycin and its derivatives. Full 1H and 13C assignment, motional behavior, dimerization and complexation with Ac-D-Ala-D-Ala. AB - Complete 1H and 13C NMR assignments are presented for eremomycin (1) and some of its desglycosylated derivatives 2, 3 and compared to the structurally closely related glycopeptide vancomycin. Primary structure and stereochemistry of eremomycin is corroborated by the present high field total correlation spectroscopy, NOESY and heteronuclear multiple-bond correlation NMR methods. A rough motional characterization of the title compound is attempted by 13C-T1 and 13C-[1H] NOE measurements. Dimerization of eremomycin is observed both in DMSO-d6 CCl4 and D2O solutions. Complexation with cell wall analogue dipeptide Ac-D-Ala-D Ala is also demonstrated. PMID- 1761418 TI - Complete amino acid sequence of phenomycin, an antitumor polypeptide antibiotic. AB - The primary structure of phenomycin, an antitumor polypeptide antibiotic isolated from the culture broth of Streptomyces fervens var. phenomyceticus, was determined. Sequence analysis has revealed that it consists of 89 amino acid residues (Mr 9,524) and no disulfide bridge is present. The sequence of phenomycin at residues 48-70 was found to be hydrophilic, being surrounded by hydrophobic regions at both sides. Furthermore, clustering of half the lysine residues in this hydrophilic region and marked basicity of phenomycin imply the external disposition of this region. Phenomycin does not show significant sequence homology to any known proteins including antitumor polypeptide antibiotics. PMID- 1761419 TI - Antifungal and antiviral activities of benanomicins and their analogues. AB - In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined. The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities. Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy. PMID- 1761420 TI - The nature of in vivo cell-killing of deoxyspergualin, and its implication in combination with other antitumor agents. AB - The mode of in vivo cell-killing by 15-deoxyspergualin (NKT-01) was assessed by measuring change of whole body radioactivity of mice inoculated with 125I iododeoxyuridine-labeled P388 leukemia cells. Although NKT-01 showed strong life prolonging effect on P388 leukemia-bearing mice, significant excretion of 125I was not observed within 4 days after the start of treatment with NKT-01. Thereafter, the remaining 125I was reduced gradually and reached about half of control level on day 7. Colony forming ability in soft agar media of peritoneal tumor cells taken after completion of 5-day treatment with NKT-01 was markedly reduced to less than 3%. These results suggested that life prolongation of NKT-01 was produced both by a cytostatic effect, which lasts for an extraordinarily long period, and by a subsequent cytotoxic effect. Cell cycle distribution analysis using flow cytometry showed the cytostatic action of NKT-01 caused G0/G1 arrest of the tumor cells. Therefore, the drug-sensitive cycling population of the tumor cells was reduced, and combination with other antitumor agents was antagonistic, if they were administered simultaneously or consecutively with NKT-01. In contrast, if the other drugs such as cyclophosphamide, cisplatin and cytosine arabinoside, were administered prior to NKT-01, a synergistic combination effect was obtained. This synergism might be due to prolongation of the period of cell cycle perturbation caused by other drugs (such as G2 arrest by cisplatin) by the cytostatic effect of NKT-01. Although the precise mechanisms of the cytostatic action of NKT-01 remain unclear, it might play an important role in the combination with other antitumor drugs. PMID- 1761421 TI - The effect of methylation inhibitors on citreamicin biosynthesis in Micromonospora citrea. AB - When the citreamicin-producing organism Micromonospora citrea NRRL 189351 was incubated in the presence of the methylation inhibitors sinefungin or aminopterin, biosynthesis of the zeta component was stimulated approximately 20 to 200-fold above the level normally produced. Inhibition of a second methylation reaction, which is superficially very similar to the first, was not detected. Other known methylation inhibitors failed to yield any change in the natural pattern of citreamicins produced. This approach is an excellent route for preparing citreamicin zeta, which can be used as a substrate for semi-synthesis or for further biosynthetic studies. PMID- 1761422 TI - "In vitro" synthesis of different naturally-occurring, semisynthetic and synthetic penicillins using a new and effective enzymatic coupled system. AB - Forty-seven different penicillins, including some of great clinical importance, have been synthesized "in vitro" by coupling the newly described enzyme phenylacetyl-CoA ligase (PCL) from Pseudomonas putida and acyl-CoA: 6 aminopenicillanic acid (6-APA) acyltransferase (AT) from Penicillium chrysogenum. Incubations were carried out at 30 degrees C in 50 mM HCl-Tris buffer pH 8.0. The reaction mixtures contained 6-APA, CoA, ATP, dithiothreitol, Mg2+ and the corresponding penicillin side-chain precursor. This is the first description of the enzymatic synthesis of all the natural penicillins known, many of the semisynthetic until now reported, and some penicillins that could only be currently obtained by chemical synthesis. The efficiency of this prokaryotic eukaryotic enzymatic-coupled system and its application to the synthesis of different beta-lactam antibiotics are discussed. PMID- 1761424 TI - Transduction of plasmid DNA containing the ermE gene and expression of erythromycin-resistance in streptomycetes. PMID- 1761423 TI - Amphidinolide F, a new cytotoxic macrolide from the marine dinoflagellate Amphidinium sp. PMID- 1761425 TI - Mycinamicins, new macrolide antibiotics. XII. Isolation and structural elucidation of mycinamicins X and XI. PMID- 1761426 TI - Respinomycin A1, a new anthracycline antibiotic. PMID- 1761427 TI - 8-Methoxygriseorhodin C, a new member of griseorhodin antibiotic. PMID- 1761428 TI - Isolation and structural elucidation of sekothrixide, a new macrolide effective to overcome drug-resistance of cancer cell. PMID- 1761429 TI - Isolation and structure determination of a novel phosphatidylinositol turnover inhibitor, piericidin B1 N-oxide. PMID- 1761431 TI - Stephen P. Lapage. PMID- 1761430 TI - Studies on the biosynthesis of fosfomycin. 2. Conversion of 2-hydroxypropyl phosphonic acid to fosfomycin by blocked mutants of Streptomyces wedmorensis. PMID- 1761432 TI - Bacterial life at low temperature: physiological aspects and biotechnological implications. PMID- 1761433 TI - Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia. AB - The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, hydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, beta-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed. PMID- 1761434 TI - Plasmid profiles and curing of plasmids in Lactobacillus plantarum strains isolated from green olive fermentations. AB - Plasmid profiles of 35 Lactobacillus plantarum strains isolated from different green olive fermentors were obtained. A large number of plasmids in the CCC form (from 5 to 16) were present in all the tested strains as confirmed by a second dimension electrophoresis of DNA. These plasmids, all of which remain cryptic, ranged from 2.0 to 68 kb in size. Novobiocin, sodium dodecyl sulphate and ethidium bromide were used as plasmid-curing agents but only novobiocin induced loss of extrachromosomal DNA at a high frequency in these strains. PMID- 1761435 TI - High frequency transformation of Streptomyces niveus protoplasts by plasmid DNA. AB - A procedure has been developed for transforming protoplasts of the novobiocin producing strain Streptomyces niveus at high frequency. This required the isolation of strains LH13 and LH20 defective in DNA restriction from the wild type (ATCC 19793) which is transformed at very low frequencies. The LH13 and LH20 derivatives were obtained by curing pIJ702 DNA from the few S. niveus transformed protoplasts obtained by transformation of the wild type with high concentrations of pIJ702 DNA. Protoplasts of S. niveus strains LH13 and LH20 produced about 10(6) transformants/micrograms DNA with modified pIJ702 DNA derived by replication in S. niveus. Unmodified DNA (derived from replication in S: lividans) from a series of pIJ101, SCP2 and pSN2-based derivatives, gave transformation frequencies in the range of 10(2)-10(3) transformants/micrograms DNA. Optimal conditions for the formation and transformation of S. niveus protoplasts are described. PMID- 1761436 TI - A dot-immunobinding assay for the laboratory diagnosis of tuberculous meningitis and its comparison with enzyme-linked immunosorbent assay. AB - In an attempt to establish an alternative to standard bacteriological methods in the laboratory diagnosis of tuberculous meningitis (TBM), a simple dot immunobinding assay (Dot-Iba) was standardized to detect Mycobacterium tuberculosis antigen 5 and antimycobacterial antibody in cerebrospinal fluid (CSF) specimens of patients with TBM. Sensitivity and specificity of Dot-Iba was compared with conventional enzyme-linked immunosorbent assay (ELISA) and standard bacteriological techniques. The Dot-Iba showed excellent correlation with indirect ELISA for the detection of antimycobacterial antibody in CSF and showed 60% sensitivity and 100% specificity in culture-negative patients with TBM. However Dot-Iba was less sensitive for the detection of antigen 5 in CSFs and showed false negative results (60%) in culture-positive patients with TBM. PMID- 1761437 TI - Continued successful operation of open-fronted microbiological safety cabinets in a force-ventilated laboratory. AB - The considerable refinements necessary to enable Class I and II microbiological safety cabinets to operate in a force-ventilated laboratory and to meet appropriate safety criteria have been reported previously. The continued successful operation of such cabinets without a deterioration of operator protection is described. The performance of two Class II units, one meeting and one failing the current British Standard applied to four head KI-discus testing, is compared and discussed. In addition, some further potential difficulties within the environment, which could compromise cabinet containment, are highlighted. PMID- 1761438 TI - Mercuric reductase activity in the adaptation to cationic mercury, phenyl mercuric acetate and multiple antibiotics of a gram-negative population isolated from an aerobic fixed-bed reactor. AB - Eighty-eight strains, isolated from an aerobic fixed-bed reactor and identified to the genus level, were examined for resistance to 21 antibiotics, cationic mercury and phenylmercuric acetate. All except three were able to grow on Mueller Hinton agar plates containing 8 micrograms/ml mercuric chloride, but only 42 exhibited a mercuric reductase and an organomercurial lyase activity. Furthermore, 82 of them were multiply-antibiotic resistant, whereas no positive correlation between this property and cationic mercury volatilization capacity was found. It was concluded that this bacterial community-adapted response to these selective agents, which has been most often shown to be mediated by R plasmids, was the result of two independent phenomena. Moreover, the high percentage of multiple antibiotic and mercury resistance found in this population suggested that simultaneous selections occurred on filters of bacteria which exhibited mucoid colonies and tolerance to these two categories of stress agents. PMID- 1761439 TI - Analysis of quantal response data from bacterial destruction studies in sterilization: the Stumbo estimate is biased. AB - Real and simulated experimental data and theoretical data from quantal response experiments were used to make a comparison between the analysis of data from a quantal response experiment and data from a direct enumeration experiment. The method of analysis for each is differentiated, thereby enhancing the utility of the quantal response experiment in sterilization studies. From this comparison it appears that the Stumbo estimate of the D value is biased. Furthermore, the Stumbo estimate depends upon the spore load per replicate in quantal response type experiments, which makes experimental comparisons difficult. Another estimate of D is demonstrated which overcomes some of these shortcomings. PMID- 1761440 TI - Typing of Proteus mirabilis from clinical sources by computerized analysis of electrophoretic protein patterns. AB - Seventy-five strains of Proteus mirabilis (mainly of human origin) were characterized by one-dimensional SDS-PAGE of cellular proteins. The strains came from various countries; 24 were from urine, 17 from faeces (including one from a dog and one from a monkey), 12 from the respiratory tract (including nine from sputum), four from a cerebral abscess, 12 from miscellaneous sources and six from unknown sources. The protein patterns, which contained 45 to 50 discrete bands, were highly reproducible. The patterns of the 75 P. mirabilis cultures plus those of the type strains of six Proteus and Providencia species were used as the basis for two numerical analyses. In the first, which included all the protein bands, the P. mirabilis cultures formed nine clusters at the 85% S level. In the second analysis, in which the principal protein bands (in the 34.0-44.6 kDa range) were excluded, 74 of the 75 cultures of P. mirabilis formed a single cluster at the 77% S level distinct from the six Proteus and Providencia reference strains. The P. mirabilis strain which failed to cluster with the others had a background band pattern typical of the species in the lower molecular weight region but appeared to be less typical in the heavier bands. It is concluded that high resolution PAGE combined with computerized analysis of protein patterns provides the basis for typing clinical strains of P. mirabilis. Reference strains of each of the nine PAGE types identified are available from NCTC for inclusion in future studies. PMID- 1761441 TI - Detection of glycopeptide resistance in clinical isolates of gram-positive bacteria. PMID- 1761442 TI - Management of biliary tract infections: potential role of the quinolones. PMID- 1761443 TI - Uptake of 3H-norfloxacin in methicillin-resistant Staphylococcus aureus. AB - To examine the possibility of a proton-motive efflux pump for quinolones in highly quinolone-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), we studied 3H-norfloxacin uptake in two quinolone resistant and two quinolone-sensitive strains of MRSA whose gyrA region surrounding amino acid codons 84 and 85 had been sequenced. Two strains were related (one sensitive and one resistant) in that both were recovered from a single patient, one before (sensitive) and one after (resistant) ciprofloxacin therapy. Drug uptake was assessed in four separate experiments running triplicate bacterial suspensions with radiolabeled drug added at time = 0. Sampling was performed in 10 min increments up to 50 min by a vacuum filtration method. The ionic uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCPH), was added at 40 min to test inhibition of a pump mechanism. The results demonstrated no statistically significant differences in uptake between the sensitive and resistant groups, and the uptake patterns were similar. CCCPH also induced an equivalent surge, or enhanced uptake among these strains, rendering an energy dependent efflux pump an unlikely contributor to the high levels of resistance seen in our strains. Our findings support parallel studies done on these isolates that implicate mutational changes at amino acid codon 84 and/or codon 85 in the gyrA gene as an explanation for high-level quinolone resistance (MIC to ciprofloxacin greater than or equal to 16 mg/L) in MRSA. PMID- 1761444 TI - Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes. AB - An imipenem-resistant strain, Enterobacter aerogenes EA-Z, was isolated from a blood culture. Outer membrane protein (OMP) profiles indicated the loss of a 40 kDa OMP, decreased expression of 42 and 44 kDa OMPs, and increased expression of a 50 kDa OMP in strain EA-Z when compared with imipenem-susceptible clinical isolates of E. aerogenes. The OMP profile of EA-Z was similar to that of strain EA-SI16, an imipenem-resistant E. aerogenes second-step mutant selected on imipenem-containing media. A single-step imipenem-resistant mutant, EA-SI8, had lost expression of only the 40 kDa OMP. No new beta-lactamase could be detected by isoelectric focusing, and no increase in imipenem hydrolysis was seen when EA Z was compared with imipenem-sensitive controls, even in the presence of added zinc. These data suggest that the 40 kDa OMP of E. aerogenes might be required for the normal diffusion of imipenem across the outer membrane. PMID- 1761445 TI - Quantification of in-vitro post-antibiotic effect based on the mean recovery time. I: Theoretical perspectives and a practical procedure. AB - An empirical description of the post-antibiotic effect has been previously proposed on the basis of the time required for the bacterial density to increase by one log10 following antimicrobial exposure. In this study, a set of theoretical perspectives are established and the post-antibiotic effect quantitatively defined based on the mean-recovery time. The mean recovery-time can be determined by measuring the area above the growth curve of a bacterial population following antimicrobial exposure. It can be shown that the previously proposed description of the post-antibiotic effect may be regarded as a special case of the definition based on the mean-recovery. Furthermore, a practical procedure is described for the quantitation of the post-antibiotic effect from a given set of data in the form of a growth curve. PMID- 1761446 TI - Quantification of in-vitro post-antibiotic effect based on the mean recovery time. II: A comparison of colony counting versus photometric methods for the determination of bacterial growth. AB - In the preceding paper, a method for the quantification of the post-antibiotic effect (PAE) has been developed based upon the mean recovery-time of an antibiotic-treated bacterial population, showing that the mean recovery-time is determined by the area above a growth curve of the bacterial population. Such an area determination of PAE implies that this method is less likely to be influenced by the early portion of a growth curve and therefore less dependent on the ability of a technique to detect a minimum bacterial density (sensitivity limit). In this study, this implication is further demonstrated in theory and through experimentation. As a result, an approach to estimation of contribution of the early portion of a growth curve to the quantitation of PAE based on the mean recovery-time is derived. The PAE of ciprofloxacin on Escherichia coli ATCC 25922 was determined under different test conditions using colony count and optical density measurements for determining bacterial growth. Differences in durations of the PAE quantitated by the mean recovery-time from the colony count measured and optical density measured growth curves were not statistically significant (P greater than 0.05). PMID- 1761447 TI - Synergic post-antibiotic effect of mecillinam, in combination with other beta lactam antibiotics in relation to morphology and initial killing. AB - The synergic in-vitro post-antibiotic effect (PAE) of mecillinam, in combination with either ampicillin, aztreonam, ceftazidime or piperacillin, on a reference strain of Escherichia coli was evaluated by bioluminescence assay of bacterial ATP. Ampicillin, ceftazidime and mecillinam alone induced a concentration dependent PAE (greater than 3 h) on E. coli, whereas aztreonam and piperacillin alone induced a short (less than 1 h) non-dose dependent PAE. At most concentrations, the combination of mecillinam and ampicillin, aztreonam, ceftazidime or piperacillin induced longer PAEs on E. coli than the sum of the individual antibiotics' PAEs. Long PAEs were seen concomitantly with the presence of spheroplasts. In addition to the synergistic PAE, the decrease in colony counts and changes in ATP values after a 2 h exposure to mecillinam, in combination with the other beta-lactam antibiotics, were more prominent than the respective values after exposure to the individual antibiotics. The change in ATP was generally less pronounced than the decrease in colony counts. This could be due to lysis of spheroplasts on agar plates, leading to an over-estimation of the initial killing when assayed by viable counting. Mecillinam, which induced long PAEs on E. coli at almost all concentrations in this study, has a high affinity for penicillin binding protein 2 (PBP 2) and induced spheroplast formation at all concentrations. However, mechanisms other than the affinity for PBP 2 and spheroplast formation are involved in the PAE of beta-lactam antibiotics on Gram negative bacteria; since the PAE was prolonged when mecillinam was combined with ampicillin, aztreonam, ceftazidime or piperacillin, which bind preferentially to PBP 1 and 3. PMID- 1761448 TI - Killing kinetics of cefuroxime axetil against Haemophilus influenzae in an in vitro model simulating serum concentration profiles after oral administration. AB - We have used a dynamic in-vitro model to determine the killing kinetics of two formulations of cefuroxime axetil against 18 clinical strains of Haemophilus influenzae. The concentration of cefuroxime axetil was adjusted dynamically to simulate the mean serum profile in healthy volunteers following the administration of a single 250 mg dose in oral suspension or tablet form. Bacterial numbers were reduced by 3 log10 cfu/mL during the eight-hour experimental period with both dosage form simulations. Our results suggest that cefuroxime axetil, 250 mg in oral suspension or tablet form, may protect against the dissemination of H. influenzae during episodes of bacteraemia. PMID- 1761449 TI - beta-Lactamase produced by a highly beta-lactam-resistant strain of Bacteroides fragilis: an obstacle to the chemotherapy of experimental mixed infections. AB - A strain of Bacteroides fragilis, which produces a metallo-beta-lactamase, was inoculated into pouches on the backs of rats together with a beta-lactamase negative Escherichia coli highly sensitive to beta-lactam antibiotics. The mixed infection rat pouch model was treated with either flomoxef (susceptible to hydrolysis by the beta-lactamase produced by B. fragilis), or cefmetazole (relatively resistant to hydrolysis). In this model of mixed infection flomoxef showed weak in-vivo activity against E. coli, although showing the same strong activity in a model of single infection with E. coli. On the other hand, cefmetazole showed strong activity against E. coli, even in the model of mixed infection. The concentrations of both drugs in the pouches were decreased in infections with the strain of B. fragilis. There was a greater decrease in the concentration of flomoxef than of cefmetazole. Flomoxef was unstable whereas cefmetazole was relatively stable in the pouch exudates that had been infected with B. fragilis. These experimental data suggest that bacteria that produce a metallo-beta-lactamase decrease the in-vivo efficacy of beta-lactam antibiotics against other co-infecting bacteria. Thus, it is suggested that it is important in the chemotherapy of mixed bacterial infections that include these highly resistant beta-lactamase-producing bacteria to use antibiotics that are stable to hydrolysis by these enzymes. PMID- 1761450 TI - Dosage adjustment and clinical outcomes of long-term use of high-dose tobramycin in adult cystic fibrosis patients. AB - A two-phase study was undertaken designed to investigate the impact of computer aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis. In phase one, a baseline (historical control) study of drug use patterns was performed. During the second phase, patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were randomly allocated to one of two schedules. Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocols using serum tobramycin assay data determined three times weekly. Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population-based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression. The agreed therapeutic target was a peak serum tobramycin concentration of 8-10 mg/L and a trough concentration of 1-2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges (group A-14%; group B 34.7%, chi 2 test, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761451 TI - A randomized trial of cefepime (BMY-28142) and ceftazidime for the treatment of pneumonia. AB - Cefepime is a new cephalosporin with a broad antimicrobial spectrum that includes Staphylococcus aureus and Pseudomonas aeruginosa. To study the efficacy and safety of cefepime for treatment of pneumonia, 65 patients were randomized to therapy with either cefepime or ceftazidime at a two to one ratio. Of the 57 evaluable patients, 89% of the cefepime patients and 84% of the ceftazidime patients were cured clinically or improved. Haemophilus spp., Streptococcus pneumoniae, and Neisseria spp. were common pathogens. Bacteriological cure was achieved in 31 (91%) of cefepime patients and 17 (100%) ceftazidime patients. Adverse clinical and laboratory reactions possibly due to study drug occurred in 9 (21%) cefepime patients and in 1 (5%) ceftazidime patient. Most reactions were mild and resolved with discontinuation of study drug. In this study, cefepime appeared as effective as ceftazidime for the treatment of pneumonia. PMID- 1761452 TI - Ceftibuten versus cefaclor for the treatment of bronchitis. AB - Ceftibuten is an oral third generation cephalosporin with potent antimicrobial activity against Enterobacteriaceae, beta-lactamase positive Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Neisseria gonorrheae, penicillin-susceptible pneumococci, and beta-hemolytic streptococci. To study the efficacy and safety of ceftibuten for treatment of bronchitis, 58 patients were randomized to therapy with either ceftibuten 400 mg once a day or cefaclor 250 mg every 8 h at a ratio of two to one. Of 45 clinically evaluable patients, 28 (87.5%) of the 32 ceftibuten patients and 12 (92.3%) of the 13 cefaclor patients were clinically improved or cured. Of 33 microbiologically evaluable patients, 21 (87.5%) of the 24 ceftibuten patients and eight (80%) of the ten cefaclor patients were cured. Of 56 patients evaluable for adverse effects, three (7.9%) of the 38 ceftibuten patients and one (5.6%) of the 18 cefaclor patients had adverse reactions. In this small study, once-daily ceftibuten appeared as safe and as effective as cefaclor for the treatment of bronchitis. PMID- 1761453 TI - Comparative efficacy and safety of cefprozil and cefaclor in the treatment of acute uncomplicated urinary tract infections. AB - Cefprozil is a new oral semi-synthetic cephalosporin with broad antibacterial spectrum and prolonged serum elimination half-life. In vitro, cefprozil demonstrates excellent activity against common urinary tract pathogens such as Escherichia coli and Klebsiella pneumoniae. Cefprozil, 500 mg once a day, was compared to cefaclor, 250 mg three times a day, in an open, randomized, comparative, clinical trial for the treatment of acute, uncomplicated, urinary tract infection. One hundred and two adult patients were eligible for safety evaluation; four patients were excluded due to side-effects (abdominal discomfort, nausea and vomiting). Ninety-eight patients were eligible for evaluation of efficacy. Clinical and bacteriological responses were comparable for both antibiotics. Leucopenia, nausea, and vaginal yeast infections were slightly more common in the cefprozil group. Cefprozil, 500 mg once daily, appears to be an appropriate alternative for the treatment of acute, uncomplicated urinary tract infections. PMID- 1761454 TI - Plasmid-associated resistance to pivmecillinam in Shigella flexneri and Shigella boydii. PMID- 1761455 TI - Reduced uptake of ciprofloxacin in a resistant strain of Neisseria gonorrhoeae and transformation of resistance to other strains. PMID- 1761456 TI - Susceptibility testing of cefpodoxime. PMID- 1761457 TI - Dependence of the interaction of ceftazidime and gentamicin against Pseudomonas aeruginosa on the bacterial growth-rate. PMID- 1761458 TI - Imipenem resistance in Proteus mirabilis. PMID- 1761459 TI - Activity of free and liposome encapsulated streptomycin against Mycobacterium avium complex (MAC) inside peritoneal macrophages. PMID- 1761460 TI - Interference of cefpirome with the measurement of plasma creatinine. PMID- 1761461 TI - Influence of ventrolateral surface of medulla on tracheal gland secretion. AB - Airway secretion can be modified reflexly as well as locally. Previous studies indicate that neurons in a circumscribed region near the ventral surface of the medulla (VMS) can substantially modify airway tone and reflex responses to vagal inputs. In the present studies we assessed the importance of these neurons on tracheal gland secretion. We examined the changes in the number of hillocks of secretion appearing from submucosal glands in an exposed field of tracheal epithelium (1.2 cm2) coated with tantalum dust before and after interventions on the VMS. Experiments were performed in alpha-chloralose-anesthetized dogs paralyzed and ventilated with 40% O2. Stimulation of nicotinergic receptors by application of a pledget containing nicotine in 11 dogs caused a significant elevation in tracheal gland secretion in the subsequent 60 s, compared with a control period in which buffered saline was applied. Prior application of lidocaine or hexamethonium bromide to the VMS blocked the effect of topically applied nicotine. The central effects of nicotine were diminished by atropine methylnitrate given intravenously. In addition, lidocaine application to the VMS or focal cooling of intermediate areas to between 20 and 15 degrees C significantly decreased secretion rates reflexly produced by capsaicin-induced stimulation of pulmonary C-fiber receptors and by mechanical stimulation of the carina and larynx. These findings suggest that the ventral medulla contains cells near its surface that influence tracheal fluid secretion and modulate reflex responses of airway submucosal glands, probably by altering the level of general excitation within the central respiratory integrating circuits. PMID- 1761462 TI - Organ blood flow in Fischer-344 rats bearing MCA-induced sarcoma. AB - Although blood flow is central to systemic metabolism, little is known about the effect of tumor on the perfusion of host tissues. This study evaluated the effects of a methylcholanthrene-induced sarcoma on blood flow to intra-abdominal organs and skeletal muscle of Fischer-344 rats anesthetized with pentobarbital sodium. Animals were studied by aortic injection of radiolabeled microspheres when the tumors reached 20% of body weight. Total-organ arterial flows in spleen, liver, small intestine, and pancreas were each increased to 50-150% in tumor bearers relative to controls (P less than 0.05). Portal venous flow and flow per gram to hindlimb muscle were 60 +/- 20 and 300 +/- 100% greater, respectively, in tumor-bearing animals (P less than 0.005). This study shows that tumor growth can be associated with large changes in organ flow and distribution of cardiac output. The increase in skeletal muscle flow in the tumor bearers, which lost normal tissue weight relative to pair-fed controls (P less than 0.05), is in marked contrast to decreased muscle flow previously observed in simple starvation. PMID- 1761463 TI - Alveolar and lung liquid clearance in the absence of pulmonary blood flow in sheep. AB - The effect of removing pulmonary blood flow on the clearance of excess liquid and protein from the air spaces and interstitium of the normal lung was studied in anesthetized ventilated sheep. To eliminate pulmonary blood flow to one lung, the left pulmonary artery was occluded. Autologous serum (3 ml/kg) with 125I-labeled albumin was then instilled into the left lower lobe. Hemodynamics and lung lymph were measured, and the lungs were removed after 4 h. Alveolar protein concentration over 4 h was used as the index of alveolar liquid clearance. Total lung liquid clearance was measured by the gravimetric method. The percent increase in alveolar protein concentration over baseline was similar between sheep without pulmonary blood flow (33.8 +/- 17.4) and with pulmonary blood flow (31.1 +/- 14.6); thus, alveolar liquid clearance was not changed by the absence of pulmonary blood flow. Also, in the absence of pulmonary blood flow, lung liquid clearance (as percent of instilled) over 4 h was 27.1 +/- 3.8 (n = 7), which was not significantly different from control experiments with pulmonary blood flow (26.4 +/- 7.1, n = 7). In the sheep without pulmonary blood flow, bronchopulmonary anastomotic flow was 41.5 +/- 21.3 ml/min. To further reduce blood flow to the lung, both the left pulmonary artery and the bronchoesophageal artery were occluded, which reduced bronchopulmonary anastomotic flow to the left lung to 12.0 +/- 9.3 ml/min. This further reduction in blood flow did not, however, change alveolar or lung liquid clearance. Even with this low blood flow to the left lung, the removal of 125I-albumin from the lung was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761464 TI - Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis. AB - To investigate factors that determine bronchoalveolar lavage (BAL) cellularity in patients with idiopathic pulmonary fibrosis (IPF), we compared BAL cells in patients with IPF (n = 83) to both nonsmoking (n = 111) and smoking (n = 19) normal volunteers. Patients with IPF had higher concentrations of BAL total cells and alveolar macrophages than nonsmoking volunteers and more BAL neutrophils and eosinophils than normal volunteers regardless of smoking status. Among patients with IPF, the numbers of alveolar macrophages, neutrophils, or eosinophils were strongly associated with either smoking status or pack-years of cigarette smoking. In fact, after accounting for cigarette smoking, using multivariate analysis, the only additional factors that were found to be associated with BAL cellularity were age (macrophages and eosinophils) and the percent predicted forced expired volume in 1 s (neutrophils). Additional multivariate models failed to identify a significant relationship between BAL cellularity and either the type of immunosuppressive therapy or other physiological measures of lung function. We conclude that cigarette smoking strongly influences BAL cellularity in patients with IPF. These findings suggest that cigarette smoking may have a role in the pathogenesis of IPF or may adversely affect the prognosis in patients with IPF. PMID- 1761465 TI - Effect of estradiol on tissue glycogen metabolism and lipid availability in exercised male rats. AB - The effect of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil 1.100 g body wt-1) on exercise performance, tissue glycogen utilization, and lipid availability was determined in male rats. In experiment 1, estradiol or oil was administered 1 h or 1-6 days before a treadmill run to exhaustion. No differences in body weight between oil- and estradiol-administered animals were observed during the 6-day treatment. Animals receiving estradiol for 3-6 days ran significantly longer and completed more work than oil-administered animals. Significant degradation of red and white vastus muscle, myocardial, and liver glycogen was observed in all animals run to exhaustion. In experiment 2, animals were administered estradiol for 5 days and then run for 2 h. The submaximal run for 2 h significantly reduced tissue glycogen content in red and white vastus muscle, heart, and liver of oil-administered animals. The latter effect was attenuated in both vastus muscles, liver, and myocardial tissues in the estradiol administered animals. Estradiol administration significantly increased plasma fatty acids and lowered plasma lactate during the submaximal run. These data indicate that when body weight remained constant between groups of male rats, estradiol administration for 3-6 days increased exercise performance. Furthermore, estradiol administration for 5 days resulted in greater lipid availability and less tissue glycogen utilization during submaximal running for 2 h. PMID- 1761466 TI - Distensibility of small arteries of the dog lung. AB - To obtain in situ measurements of the distensibility of small (100- to 1,000 microns-diam) pulmonary arterial vessels of the dog lung, X-ray angiograms were obtained from isolated lung lobes with the vascular pressure adjusted to various levels. The in situ diameter-pressure relationships were compared with the diameter-pressure relationships for small arteries that were dissected free from the lungs and cannulated with small glass pipettes for the measurement of diameter and transmural pressure. The diameter-vascular or diameter-transmural pressure curves from both in situ and cannulated vessels were sufficiently linear in the pressure range studied (0-30 Torr) that they could be characterized by linear regression to obtain estimates of D0, the diameter at zero vascular pressure, and beta, the change in diameter (micron) per Torr change in pressure. The vessel distensibility coefficient (alpha) was defined as alpha = beta/D0. The mean values of alpha were approximately 2.0 +/- 0.8%/Torr (SD) for the in situ vessels and 1.7 +/- 0.6%/Torr for the cannulated vessels, with no statistically significant difference between the two methods. The influence of vasoconstriction elicited by serotonin was evaluated in the in situ vessels. Serotonin-induced vasoconstriction caused a decrease in D0 and little change in alpha. PMID- 1761467 TI - Inhomogeneous response of expiratory muscle activity to cold block of the ventral medullary surface. AB - We assessed the effects of cooling the ventral medullary surface (VMS) on the activity of chest wall and abdominal expiratory muscles in eight anesthetized artificially ventilated dogs after vagotomy and denervation of the carotid sinus nerves. Electromyograms (EMGs) of the triangularis sterni, internal intercostal, abdominal external oblique, abdominal internal oblique, and transversus abdominis muscles were measured with EMG of the diaphragm as an index of inspiratory activity. Bilateral localized cooling (2 x 2 mm) in the thermosensitive intermediate part of the VMS produced temperature-dependent reduction in the EMG of diaphragm and abdominal muscles. The rib cage expiratory EMGs were little affected at 25 degrees C; their amplitudes decreased at lower VMS temperatures (less than 20 degrees C) but by significantly fewer degrees than the diaphragmatic and abdominal expiratory EMGs at a constant VMS temperature. With moderate to severe cooling (less than 20 degrees C) diaphragmatic EMG disappeared, but rib cage expiratory EMGs became tonic and resumed a phasic pattern shortly before the recovery of diaphragmatic EMG during rewarming of the VMS. These results indicate that the effects of cooling the VMS differ between the activity of rib cage and abdominal expiratory muscles. This variability may be due to inhomogeneous inputs from the VMS to expiratory motoneurons or to a different responsiveness of various expiratory motoneurons to the same input either from the VMS or the inspiratory neurons. PMID- 1761468 TI - Sweat lactate in exercising children and adolescents of varying physical maturity. AB - This study attempts to explain some of the individual variability in sweating pattern by comparing prepubescents and pubescents. Sweating rate and muscular anaerobic capacity are higher in adults than in children; thus we hypothesized that sweat gland anaerobic metabolism, as reflected by lactate excretion, might be higher with advanced physical maturity (PM). Lactate concentration in sweat ([LAC]sw) was measured at various stages of PM in boys who exercised in the heat. The subjects were divided into three groups on the basis of Tanner staging: prepubertal (PP, n = 16), midpubertal (MP, n = 15), and late pubertal (LP, n = 5). Subjects cycled at 50% of maximal O2 uptake for three 20-min bouts, with 10 min rest periods, in 42 degrees C and 18% relative humidity. Sweat samples were harvested, and population density of activated sweat glands was determined after each exercise bout. [LAC]sw during bout 1 was higher in PP than in LP [PP = 22.2 +/- 2.2, MP = 19.5 +/- 1.4, LP = 14.3 +/- 1.3 (SE) mmol/l]. In all groups, [LAC]sw decreased during subsequent bouts, and there were no intergroup differences in [LAC]sw during bout 3 (PP = 11.2 +/- 0.4, MP = 10.6 +/- 0.5, LP = 9.7 +/- 0.2 mmol/l). [LAC]sw was inversely related to sweating rate. Lactate excretion rate per gland was greater with the increase in PM (PP = 61.0 +/- 8.2, MP = 79.1 +/- 11.3, LP = 99.9 +/- 11.0 pmol/min; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761469 TI - Aldosterone and prolactin response to exercise in the heat in circumpubertal boys. AB - Thermoregulatory responses to exercise in the heat, especially sweating pattern, differ between children and adults. To determine whether such differences may be related to hormonal responses and to assess the possible association between this response and physical maturation, three groups of circumpubertal boys cycled at 50% of maximal O2 uptake (three 20-min bouts with 10 min of rest between bouts) in 42 degrees C at 20% relative humidity. On the basis of Tanner staging, 11 were prepubertal (PP), 12 midpubertal (MP), and 7 late pubertal (LP). Water ingestion was encouraged to minimize dehydration. Venous blood was sampled before and immediately after the session. Changes in heart rate, rectal temperature, and percent decrease in plasma volume did not differ among groups. There was no change in plasma osmolality in any of the groups. Resting testosterone concentrations were higher with increased level of physical maturity (PP = 0.4 +/ 0.1, MP = 8.2 +/- 1.9, LP = 13.8 +/- 1.2 nmol/l; P less than 0.05). In all groups, both aldosterone (ALD) and prolactin (PRL) markedly increased after exercise in the heat (ALD: PP = 161 +/- 40 vs. 1,289 +/- 263, MP = 173 +/- 47 vs. 1,245 +/- 153, LP = 250 +/- 76 vs. 1,681 +/- 400 pmol/l; PRL: PP = 8.1 +/- 1.2 vs. 24.9 +/- 4.2, MP = 8.8 +/- 1.0 vs. 22.0 +/- 8.9, LP = 8.4 +/- 0.8 vs. 39.0 +/ 3.6 micrograms/l; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761470 TI - Influences of gender and sex hormones on hypoxic ventilatory response in cats. AB - Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761471 TI - Erythrocyte insufflation-induced protection against oxygen toxicity: role of cytokines. AB - We studied the pulmonary response of adult rats to erythrocyte (RBC) and RBC lysate insufflation to define the mechanism of RBC insufflation-induced protection against oxygen toxicity. Tracheal insufflation of 1 ml RBC (75%) or RBC lysate induced an intense pulmonary inflammatory response. Within 24 h of oxygen exposure, greater than 95% of insufflated RBCs was hemolyzed. The cell free fraction of alveolar lavage fluids from RBC- or RBC lysate-insufflated rats had similar capacity in protecting endothelial cells against H2O2 cytotoxicity. However, RBC insufflation but not RBC lysate insufflation, protected rats against oxygen toxicity. There was marked erythrophagocytosis by alveolar macrophages of RBC-insufflated rats. Insufflation of RBCs, but not RBC lysate, resulted in production of tumor necrosis factor and interleukin 1, which could be recovered by bronchoalveolar lavages. When rats were insufflated with a combination of RBC lysate and cytokines at dosages within the range of cytokine levels achievable in alveolar lavage fluids by RBC insufflation, they became tolerant to oxygen. These results suggest that endogenously produced tumor necrosis factor and interleukin 1 as a result of RBC insufflation may play an important role in RBC insufflation induced oxygen tolerance. PMID- 1761472 TI - Exercise training depletes sarcoplasmic reticulum calcium in coronary smooth muscle. AB - We examined the effects of chronic exercise training on sarcoplasmic reticulum (SR) Ca uptake, spontaneous SR Ca release, and whole-cell currents in coronary smooth muscle cells. Single coronary artery smooth muscle cells demonstrated increases in intracellular free Ca (Cai) during depolarization (measured with fura-2) that were abolished by diltiazem (10(-4) M). Diltiazem significantly inhibited (80%) refilling of the SR Ca store. The SR Ca store of exercise-trained pigs was 64% less after 11 min vs. 2 min of recovery, whereas cells from sedentary pigs showed no depletion. Exercise-training-induced depletion of the SR Ca store was abolished when ryanodine (10(-5) M) was applied during the recovery, but depletion was enhanced by low concentrations of ryanodine (10(-8) M). In smooth muscle from sedentary pigs, 10(-8) M ryanodine mimicked the effects of exercise training by depleting the SR Ca store during 11 min of recovery (54% depletion). When allowed a longer recovery without ryanodine (14 min or without prior depolarization), the SR Ca store in cells from exercise-trained pigs returned toward peak levels. The outward K current vs. voltage relationship did not differ in cells from exercise-trained or sedentary pigs. Exercise training reduced the number of spontaneous transient outward currents normally found in cells from sedentary pigs. We introduce a model that provides a rational basis to explain the results obtained in this study. PMID- 1761473 TI - Occlusion pressure response to inspiratory flow-resistive loading in anesthetized swine. AB - Conscious animals subjected to inspiratory flow-resistive loading augment respiratory drive [as measured by airway occlusion pressure (P100)] independently of changes in chemical drive. Past studies of anesthetized subjects, however, have failed to demonstrate this response, and investigators have concluded that its presence depends on a state of consciousness. We tested the hypothesis that respiratory depression due to anesthesia or endogenous opioids rather than unconsciousness per se was responsible for this observation. Miniature piglets were anesthetized with ketamine and xylazine and subjected to hyperoxic CO2 rebreathing trials with and without added inspiratory resistance, before and after treatment with the opioid antagonist naltrexone. Before naltrexone there was a parallel leftward shift in the occlusion pressure vs. PCO2 relationship without a change in slope (delta P100/delta PCO2). After naltrexone there was a 45.5 +/- 15% increase in slope with loading. Addition of incremental doses of pentobarbital markedly reduced this increase in slope. We conclude that anesthetized animals can demonstrate flow-resistive load compensation in the form of augmented neuromuscular output not due to increased chemical drive. Failure to observe this response in past studies may reflect respiratory depression due to the anesthetic agents employed. PMID- 1761474 TI - Effect of aminophylline on transpulmonary passage of venous air emboli in pigs. AB - Aminophylline has been shown to dramatically reduce the filtering capacity of the lung in dogs during venous air embolism. Similarities have been pointed out between the cardiovascular and respiratory systems of the pig and of humans. We therefore wanted to find out whether aminophylline also modifies the transpulmonary spillover of microbubbles to the arterial circulation of the pig. Twenty-eight pigs were anesthetized with pentobarbital sodium and mechanically ventilated. Aminophylline was injected intravenously into 10 of the pigs before the introduction of air bubbles into the right ventricle, while the other 18 pigs served as controls. A transesophageal echocardiographic probe was used to detect eventual air bubbles in the left atrium or in the aorta. Pigs received either air infusion, at rates varying from 0.05 to 0.20 ml.kg-1.min-1, or calibrated microbubbles, 5-300 microns diam. We found that aminophylline-treated pigs did not show any change in spillover incidence compared with controls. Furthermore, in both groups the spillover during continuous air infusion seemed to be a preterminal event, because the pigs had very low arterial pressure when arterial bubbles were observed. Finally, there was an increase in mean pulmonary arterial pressure from 18 +/- 3.4 to 26 +/- 2.2 (SD) mmHg (n = 4, P less than 0.01) in aminophylline-treated pigs after a bolus injection of microbubbles (less than or equal to 50 microns, total volume less than 0.5 ml). Our results suggest that aminophylline does not modify the transpulmonary passage of microbubbles in this porcine model. In addition, it would seem that the pulmonary circulation of the pig is sensitive to very small volumes of air, when injected as microbubbles. PMID- 1761475 TI - Decrease in functional residual capacity during inspiratory loading and the sensation of dyspnea. AB - The purposes of the present study were to determine the changes in functional residual capacity (FRC) during inspiratory loading and to examine their mechanisms. We studied seven normal subjects seated in a body plethysmograph. In both graded inspiratory elastic (35, 48, and 68 cmH2O/l) and resistive (21, 86, and 192 cmH2O.l-1.s) loading, FRC invariably decreased from control FRC and phasic expiratory activity increased. The reduction in FRC was greater with greater loads. A single inspiratory effort against an inspiratory occlusion at three different target mouth pressures (-25, -50, and -75 cmH2O) and durations (1, 2, and 5 s) also resulted in a decrease in FRC with an increase in expiratory electromyogram activity in the following expiration. The decrease in FRC was greater with greater target pressure and duration. This decrease in FRC is qualitatively similar to that during inspiratory loaded breathing, and we suspect that the same mechanisms are at work. Because neither vagal nor chemoreceptor reflex can account for these responses, we suspect conscious awareness of breathing or behavioral control to be responsible. In an additional study, the sensation of discomfort of breathing during elastic loading decreased with a decrease in FRC. These results suggest that the reduced FRC may be due to behavioral control of breathing to reduce the sensation of dyspnea during inspiratory loading. PMID- 1761476 TI - Role of vagal afferents in the control of abdominal expiratory muscle activity in the dog. AB - We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers. PMID- 1761477 TI - High rates of exogenous carbohydrate oxidation from starch ingested during prolonged exercise. AB - This study compared the gastric emptying and oxidation of two 15% carbohydrate (CHO) solutions: a 22-chain-length glucose polymer (GP) and soluble starch (SS). Six endurance-trained subjects ingested 1,200 ml of either GP or SS while cycling for 90 min at 70% of maximal oxygen consumption (VO2max). Whereas the calculated total CHO oxidation (GP 266.8 +/- 41.9 g; SS 263.6 +/- 28.9 g) and the volume emptied from the stomach (GP 813 +/- 130 ml; SS 919 +/- 116 ml) were similar, the appearance of the 14C label in plasma occurred more rapidly from ingested SS than from GP (P less than 0.001). This resulted in a significantly greater rate of SS oxidation than that from GP (SS 105.9 +/- 21.9 g, GP 49.6 +/- 10.2 g; P less than 0.001). Exogenous CHO oxidation from GP accounted for 19% of total CHO oxidation, whereas the corresponding value for SS was 40%. This study suggests that the oxidation of SS and GP solutions ingested during exercise at 70% VO2max is not limited by gastric emptying. Rather, it appears to be either the rate of digestion or absorption of these solutions that determines their utilization. PMID- 1761478 TI - Airways impedance during single breaths of foreign gases. AB - The changes in airways resistance (Raw) and inertance (Iaw) during single inspirations of pure methane, helium, neon, and ethane at a flow of 0.1 l/s were measured in six healthy subjects by use of a forced-oscillation technique. Raw and Iaw were computed from respiratory transfer impedance obtained at a frequency of 20 Hz by applying pressure oscillations at the chest and measuring flow at the mouth with a bag-in-box system. Compared with the air data, the changes of Iaw after inhalation of 500 ml of gas averaged -41.1% with methane, -82.8% with helium, -25.8% with neon, and +4.8% with ethane. These changes were slightly less than the changes in gas density (-45%, -86%, -31%, and +5%, respectively). The inhaled volumes at which 50% of the changes had occurred (V50) did not differ significantly among gases and were approximately 100 ml. For Raw the data were more noisy than for Iaw; they were discarded in two subjects because of a strong and irreproducible volume dependence in air. Consistent differences were seen between the remaining subjects, one of whom exhibited a predominant viscosity dependence of Raw, one a predominant density dependence, and two an intermediate pattern. V50s were larger for Raw than for Iaw, indicating a more peripheral distribution of Raw. For Raw, V50s were lower with helium than with methane, in agreement with the notion that density-dependent resistance is located mainly in the large airways. The results suggest that some information on the serial distribution of Raw and Iaw may be derived from impedance measurements with foreign gases. PMID- 1761479 TI - Low-intensity training produces muscle adaptations in rats with femoral artery stenosis. AB - The effectiveness of a mild-intensity exercise program to induce adaptations within skeletal muscle of animals with peripheral arterial insufficiency was evaluated using an isolated perfused hindlimb preparation at a muscle blood flow similar to the peak found in vivo. Adult rats were subjected to bilateral femoral artery stenosis sufficient to limit peak blood flow during exercise but not alter resting blood flow. Stenosed-trained (Sten-Trained) rats walked on a treadmill at an easily achieved speed (20 m/min with a 15% grade) 5 days wk. Exercise tolerance improved from 10 min initially to 2 h/day. Non-stenosed-sedentary (Non Sten-Sed) and stenosed-sedentary (Sten-Sed) animals were limited to cage activity. Oxygen delivery to the contracting muscles was similar among groups (7.0 +/- 0.4, 7.3 +/- 0.6, and 6.6 +/- 0.6 mumol.min-1.g-1 in Non-Sten-Sed, Sten Sed, and Sten-Trained, respectively; n = 13 each). Force development was better maintained by Sten-Trained muscle (P less than 0.001) during a sequence of tetanic contraction conditions. Peak oxygen consumption was greater (P less than 0.05) in the Sten-Trained (5.23 +/- 0.34 mumol.min-1.g-1) than in Non-Sten-Sed (4.08 +/- 0.35) and Sten-Sed (4.34 +/- 0.37) rats. The increased peak oxygen extraction (P less than 0.05) by the muscle of the Sten-Trained rats (82.5 +/- 7.1% of oxygen inflow vs. 58.7 +/- 4.7 and 57.4 +/- 5.0%, respectively) was probably related to the increased muscle capillarity and mitochondrial enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761480 TI - Fructose 1,6-diphosphate augments paraquat injury in isolated dog lungs. AB - Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride), a widely used herbicide, causes pulmonary edema by a cyclic oxidation and reduction reaction with oxygen molecules with the production of oxygen free radicals. Because fructose 1,6-diphosphate (FDP) has recently been shown to inhibit the generation of oxygen free radicals by activated neutrophils, we determined the effects of FDP on PQ-induced increase in microvascular permeability in isolated blood perfused dog lungs. Vascular permeability was assessed using the capillary filtration coefficient (Kf,c) and isogravimetric capillary pressure (Pc,i). There was no change in these variables over 5 h in the control lungs treated with saline (n = 5). A significant increase in Kf,c and a decrease in Pc,i, both of which indicated increased vascular permeability, were observed at 5 h of perfusion with 4 x 10(-3) M PQ (n = 5). Unexpectedly, an increase in microvascular permeability occurred within 4 h after administration of PQ in the lungs that were pretreated with FDP (2.7-14.2 mM, n = 6). Moreover the increases of Kf,c in the FDP-pretreated lungs were significantly greater than those in the lungs treated with PQ alone. Also, the final-to-initial lung weight ratio of the FDP-pretreated group was greater than those of the other groups. Thus the FDP dose used in the present study accentuated rather than prevented the PQ lung injury. PMID- 1761481 TI - Intramuscular accumulation of prostaglandins during static contraction of the cat triceps surae. AB - We previously demonstrated that muscle afferent endings are sensitized by exogenous prostaglandins during static contraction of skeletal muscle. The purpose of this study was to determine whether 30 s of static hindlimb contraction, induced by electrical stimulation of the cat sciatic nerve, increases the concentration of immunoreactive prostaglandin E2 (iPGE2) and 6 ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha, the stable metabolite of prostaglandin I2) in muscle tissue. In addition, the role of ischemia in augmenting prostanoid production was examined. Gastrocnemius muscle was obtained by freeze-clamping tissue, and prostaglandins were extracted from muscle homogenates and measured by radioimmunoassay. Compared with precontraction values, high-intensity (68% of maximal tension) static contraction elevated gastrocnemius iPGE2 and i6-keto-PGF1 alpha by 45 and 53%, respectively (P less than 0.01). Likewise, when blood flow to the gastrocnemius was attenuated by arterial occlusion during and 2 min before low-intensity contraction (29% maximal tension), the intramuscular iPGE2 concentration was increased by 71% (P less than 0.01). Conversely, low-intensity contraction (30% of maximal tension) and arterial occlusion without contraction did not alter the concentration of either prostanoid. Our findings demonstrate that prostaglandins accumulate in muscle during static contraction. We believe that local muscle ischemia may provide a stimulus for this phenomenon. These prostaglandins therefore are available to sensitize afferent endings responsible for reflex adjustments during static muscle contraction. PMID- 1761482 TI - Effects of environmental temperature on the venodilatory response to nitroglycerin. AB - The venodilatory response to nitroglycerin (0.8 mg sublingually) was measured in 10 healthy young male volunteers in a cool [24.3 +/- 0.6 degrees C skin temperature (Tsk)] and a warm environment (34.7 +/- 0.2 degrees C Tsk). Nitroglycerin caused mean arterial pressure to fall and heart rate to rise in both the cool (105 +/- 2 to 96 +/- 3 mmHg; 55 +/- 3 to 62 +/- 3 beats/min) and the warm environment (87 +/- 3 to 81 +/- 3 mmHg; 66 +/- 4 to 75 +/- 3 beats/min), but the fall in pressure was greater in the cool than in the warm environment. Forearm blood flow was reduced and forearm vascular resistance elevated in the cool (117 +/- 19 units; 1.15 +/- 0.08 ml.100 cc arm-1.min-1) compared with the warm environment (15 +/- 3 units; 8.60 +/- 1.89 ml.100 cc arm-1.min-1). Nitroglycerin caused forearm vascular resistance to fall in the cool but had no effect in the warm environment. Venous distensibility (increase in venous volume per 30-mmHg increase in venous pressure) was twice as great in the warm as in the cool environment (3.90 +/- 0.27 vs. 1.88 +/- 0.23 ml/100 cc arm). However, the venodilatory effect of nitroglycerin was similar in the cool and warm environments (0.79 +/- 0.10 vs. 0.67 +/- 0.13 ml/100 cc arm, respectively). Arterioles are not dilated by nitroglycerin in the warmer environment, but the venodilatory effect of nitroglycerin is quantitatively similar in the two environments. PMID- 1761483 TI - Fetal swallowing: response to graded maternal hypoxemia. AB - A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities. PMID- 1761484 TI - Accuracy of respiratory inductive plethysmograph in measuring tidal volume during sleep. AB - Respiratory inductance plethysmography (RIP) has been widely used to measure ventilation during sleep, but its accuracy in this role has not been adequately tested. We have thus examined the accuracy of the RIP by comparing tidal volume measured with RIP with that measured by a pneumotachograph in eight unrestrained normal subjects during sleep. We have also studied the effect of posture on the accuracy of the RIP. In all sleep stages the correlation between RIP tidal volume measurements and expired volume showed relatively poor correlations (mean r = 0.49-0.60), and the bias of the measurements varied widely. Changes in posture altered the correlations between the two measurements, with no systematic differences between positions. When the subjects resumed a position, the 95% confidence intervals of tidal volume measurement did not overlap the original confidence limits in that posture on 13 of 25 occasions. This study shows that the RIP does not accurately measure tidal volume during sleep in unrestrained subjects and should only be used for semiquantitative assessment of ventilation during sleep. PMID- 1761485 TI - Physiological effects of hydrogen sulfide inhalation during exercise in healthy men. AB - Occupational exposure to hydrogen sulfide (H2S) is prevalent in a variety of industries. H2S when inhaled 1) is oxidized into a sulfate or a thiosulfate by oxygen bound to hemoglobin and 2) suppresses aerobic metabolism by inhibiting cytochrome oxidase (c and aa3) activity in the electron transport chain. The purpose of this study was to examine the acute effects of oral inhalation of H2S on the physiological responses during graded cycle exercise performed to exhaustion in healthy male subjects. Sixteen volunteers were randomly exposed to 0 (control), 0.5, 2.0, and 5.0 ppm H2S on four separate occasions. Compared with the control values, the results indicated that the heart rate and expired ventilation were unaffected as a result of the H2S exposures during submaximal and maximal exercise. The oxygen uptake had a tendency to increase, whereas carbon dioxide output had a tendency to decrease as a result of the H2S exposures, but only the 5.0 ppm exposure resulted in a significantly higher maximum oxygen uptake. Blood lactate concentrations increased significantly during submaximal and maximal exercise as a result of the 5.0 ppm exposure. Despite these large increases in lactate concentration, the maximal power output of the subjects was not significantly altered as a result of the 5.0 ppm H2S exposure. It was concluded that healthy young male subjects could safely exercise at their maximum metabolic rates while breathing 5.0 ppm H2S without experiencing a significant reduction in their maximum physical work capacity during short-term incremental exercise. PMID- 1761486 TI - pH-induced effects on median frequency and conduction velocity of the myoelectric signal. AB - H+ accumulation at the sarcolemma is believed to play a key role in determining the electrophysiological correlates of fatigue. This paper describes an in vitro method to externally manipulate muscle pH while measuring the resultant effect on surface-detected median frequency (MDF) and conduction velocity (CV) parameters. Hamster muscle diaphragm strips (n = 8) were isolated with the phrenic nerve intact and placed in an oxygenated Krebs bath (26 degrees C). The muscle was clamped to a noncompliant load cell to measure isometric contractile tension. Tetanic contraction was developed via 40-Hz supermaximal stimulation of the phrenic nerve. Differential signals were recorded from three electromyogram (EMG) detection surfaces for computation of CV (via the phase shift in the EMG signals) and MDF. Repeated trials were conducted at bath pHs of 7.4, 7.0, and 6.6. Bath pH was altered by aerating predetermined concentrations of O2 and CO2 into the bath. Decreases in bath pH resulted in decreases in both initial MDF and initial CV. The differences in initial MDF and initial CV were significant (P less than 0.001) for each of the bath pH conditions. In general, the change in bath pH resulted in an equal percent change in initial MDF and initial CV. This suggests that the change in bath pH caused a decrease in CV without significantly altering the fundamental shape of the M wave. In contrast, the EMG was altered differently during stimulated contractions. During stimulation, the rate of decay of CV was 65% of the rate of decay of MDF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761487 TI - Hypoxic remodeling of the rat pulmonary arterial microcirculation assessed by microdissection. AB - Artery segments were microdissected from distal acini of the rat lung and studied by light and electron microscopy. Morphometric methods were used to quantify the structure of the wall at defined levels within the normal axial pathway and to determine the changes after 5 and 7 days of whole-animal exposure to hypobaric hypoxia at an inspiratory O2 fraction of 0.1. In the normal lung, at the level of the terminal bronchiolus, the artery wall comprised up to six layers of smooth muscle cells (SMCs). At the respiratory bronchiolar level, however, the wall contained fewer than two layers of SMCs with a consistently circumferential orientation. By the second-generation alveolar ducts (AD2), the medial layer was lost, replaced by subendothelial precursor smooth muscle cells (PCs) resembling intermediate cells. At this and the next level (AD3), the PC layer was often circumferentially discontinuous. Regression analysis of the morphometric data suggested, however, that the smallest AD3 artery is likely to have a layer of PCs but with virtually no measurable separation between them and the endothelium. The mean maximum radial diameter of SMCs decreased along the axial pathway with a significant difference between diameters at terminal bronchiolus and AD2 levels; yet the diameter of endothelial cells remained the same. After 7 days of hypoxia, no change was noted in the number of smooth muscle layers, but at the AD2 level the relative area of media in the total wall increased. This was due in part to hypertrophy of PCs, as evidenced by an increase in their mean maximum radial diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761488 TI - Neural control of the forearm cutaneous vasoconstrictor response to dynamic exercise. AB - This study was designed to evaluate the relative importance of intended effort ("central command") and of the absolute intensity of dynamic exercise to the cutaneous vasoconstrictor response to the onset of exercise in humans. Skin blood flow (laser-Doppler flowmetry) was measured from the forearm in six healthy individuals during 3-min periods of high- and low-intensity exercise with and without partial neuromuscular blockade. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow to mean arterial pressure and expressed as a percent change from rest. A rating of perceived exertion (RPE) was expressed as a subjective measure of intended effort. Under control conditions, CVC decreased by 22% (median; range 7-42%, P less than 0.05) during high intensity exercise [218 (186-268) W; RPE 16 (14-19) exertion units]. In contrast, during control low-intensity exercise [106 (88-128) W; RPE 10 (9-14) exertion units], during low-level exercise with curare [77 (54-98) W; RPE 13 (11-16) exertion units], and during maximal exercise with curare [106 (88-124) W; RPE 19 (18-20) exertion units], CVC did not change significantly. These results suggest that factors related to the activity of the exercising muscle and its metabolism rather than intended effort determine the cutaneous vasoconstrictor response to the initiation of intense dynamic exercise in humans. PMID- 1761489 TI - Relationship between inspiratory effort and breathlessness in pregnancy. AB - Using open-magnitude scaling, we compared the relationships between breathlessness, inspiratory esophageal pressure swing (delta Pes), and ventilation in pregnancy and postpartum. Thirteen healthy women performed progressive cycle exercise tests at 33 +/- 2 wk gestation and 12 +/- 3 wk postpartum. Pulmonary function and maximal transdiaphragmatic pressure did not change. Minute ventilation (VE) was greater in the third trimester. This increase was entirely due to the increase in tidal volume (VT; 0.74 +/- 0.18 vs. 0.54 +/- 0.18 liters at rest, P less than 0.01; 1.56 +/- 0.3 vs. 1.24 +/- 0.24 liters at 48 W, P less than 0.001). delta Pes (15.3 +/- 3.0 vs. 11.9 +/- 3.5 cmH2O at 48 W, P less than 0.01) and breathlessness (1.8 +/- 1.4 vs. 1.0 +/- 0.9 at 48 W, P less than 0.05) were greater in the third trimester. However, the relationships between VT and delta Pes and between delta Pes and breathlessness were identical in the two conditions. The VT-tidal abdominal volume (Vab) and Vab-tidal gastric pressure swing (delta Pga) relationships were similar in the two conditions. In conclusion, the relationship between delta Pes and breathlessness is the same in the third trimester and postpartum. The increased VE is responsible for the breathlessness in the third trimester. Despite progressive abdominal distension by the gravid uterus, the VT-Vab and Vab-delta Pga relationships were the same in the two conditions. PMID- 1761490 TI - Human serum catalase decreases endothelial cell injury from hydrogen peroxide. AB - Serum from normal human subjects contained variable amounts of catalase activity, which was inhibitable by heat, azide, trichloroacetic acid (TCA), or aminotriazole treatment. Serum also decreased hydrogen peroxide (H2O2) concentrations in vitro and H2O2-mediated injury to cultured endothelial cells. By comparison, heat-, azide-, TCA-, or aminotriazole-treated serum neither decreased H2O2 concentrations in vitro nor reduced H2O2-mediated damage to endothelial cells. We conclude that serum catalase activity can alter H2O2 dependent reactions. We speculate that variations in serum catalase activity may alter individual susceptibility to oxidant-mediated vascular disease or be a factor when added to test systems in vitro. PMID- 1761491 TI - Plasma volume expansion in humans after a single intense exercise protocol. AB - We used intense intermittent exercise to produce a 10% expansion of plasma volume (PV) within 24 h and tested the hypothesis that PV expansion is associated with an increase in plasma albumin content. The protocol consisted of eight 4-min bouts of exercise at 85% maximal O2 uptake with 5-min recovery periods between bouts. PV, plasma concentrations of albumin and total protein (TP), and plasma osmolality were measured before and during exercise and at 1, 2, and 24 h of recovery from exercise. During exercise, PV decreased by 15%, while plasma TP and albumin content remained at control levels. At 1 h of recovery, plasma albumin content was elevated by 0.17 +/- 0.04 g/kg body wt, accounting for the entire increase in plasma TP content. PV returned to control level at 1 h of recovery without fluid intake by the subjects, despite a 820 +/- 120-g reduction in body weight. At 2 h of recovery, plasma TP content remained significantly elevated, and plasma TP and albumin concentration were significantly elevated. At 24 h of recovery, PV was expanded by 4.5 +/- 0.7 ml/kg body wt (10 +/- 1%), estimated from hematocrit and hemoglobin changes, and by 3.8 +/- 1.3 ml/kg body wt (8 +/- 3%), measured by Evans blue dye dilution. Plasma albumin content was increased by 0.19 +/- 0.05 g/kg body wt at 24 h of recovery. If 1 g of albumin holds 18 ml of water, this increase in plasma albumin content can account for a 3.4-ml/kg body wt expansion of the PV. No significant changes in plasma osmolality occurred during recovery, but total plasma osmotic content increased in proportion to PV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761492 TI - Influence of electrical stimulation on a fast-twitch muscle in aging rats. AB - Recently we observed that the flexor digitorum longus muscle of the Fischer 344 rat, which is comprised primarily of type IIb muscle, does not change in size, fiber type, or physiological characteristics during senescence [Am. J. Physiol. 258 (Cell Physiol. 27): C1031-C1035, 1990]. This muscle was utilized to determine whether a predominantly fast-twitch glycolytic muscle would respond to tonic electrical stimulation (ES) with the same degree of fiber-type transformation in aging and young rats. The extent of transformation was quantified by measuring the contractile and metabolic properties, as well as the fiber-type composition, of the flexor digitorum longus muscle after ES (10 Hz, 8 h/day) imposed on the tibial nerve for periods of 0-90 days in young adult (YG; 6-8 mo), middle-aged (MA; 16-18 mo), and senescent (SN; 26-28 mo) male Fischer 344 rats. Although ES induced a IIb-to-IIa fiber-type shift in all groups, in the SN rats the shift was significantly less pronounced at the intermediate time points and remained incomplete after 90 days, compared with YG and MA rats. ES resulted in a reduction in tetanic tension (Po), which in the YG and MA rats was due to a reduction in muscle cross-sectional area. In the SN rats the reduced Po was due to a combined loss of cross-sectional area and specific tension (Po, N/cm2). Contraction and half-relaxation times were largely unaffected by ES, and maximal velocity of unloaded shortening declined throughout ES in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761493 TI - Shivering and pathological and physiological clonic oscillations of the human ankle. AB - Shivering and physiological and pathological clonus of the ankle were compared using power spectral and cross-correlation analysis of their respective electromyographic and acceleration waveforms. The major spectral peaks from each type of involuntary oscillation possessed similar frequencies (5-7 Hz). Soleus electromyographic activity was significantly correlated with the motion signal, whereas no correlation was observed between motion and tibialis anterior electromyographic signal. These data suggest that although shivering and physiological and pathological clonus are activated by different stimuli, these overt ankle oscillations may be an expression of a common spinal neuronal network. PMID- 1761494 TI - Estimation of regional cutaneous cold sensitivity by analysis of the gasping response. AB - Regional cutaneous sensitivity to cooling was assessed in males by separately immersing four discrete skin regions in cold water (15 degrees C) during head-out immersion. The response measured was gasping at the onset of immersion; the gasping response appears to be the result of a nonthermoregulatory neurogenic drive from cutaneous cold receptors. Subjects of similar body proportions wore a neoprene "dry" suit modified to allow exposure to the water of either the arms, upper torso, lower torso, or legs, while keeping the unexposed skin regions thermoneutral. Each subject was immersed to the sternal notch in all four conditions of partial exposure plus one condition of whole body exposure. The five cold water conditions were matched by control immersions in lukewarm (34 degrees C) water, and trials were randomized. The magnitude of the gasping response was determined by mouth occlusion pressure (P0.1). For each subject, P0.1 values for the 1st min of immersion were integrated, and control trial values, although minimal, were subtracted from their cold water counterpart to account for any gasping due to the experimental design. Results were averaged and showed that the highest P0.1 values were elicited from whole body exposure, followed in descending order by exposures of the upper torso, legs, lower torso, and arms. Correction of the P0.1 response for differences in exposed surface area (A) and cooling stimulus (delta T) between regions gave a cold sensitivity index [CSI, P0.1/(A.delta T)] for each region and showed that the index for the upper torso was significantly higher than that for the arms or legs; no significant difference was observed between the indexes for the upper and lower torso.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761495 TI - Effect of resistive loads on pattern of respiratory muscle recruitment during exercise. AB - In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761496 TI - Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF. AB - The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1-1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70-90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF. PMID- 1761497 TI - Lung and chest wall mechanics in microgravity. AB - We studied the effect of 15-20 s of weightlessness on lung, chest wall, and abdominal mechanics in five normal subjects inside an aircraft flying repeated parabolic trajectories. We measured flow at the mouth, thoracoabdominal and compartmental volume changes, and gastric pressure (Pga). In two subjects, esophageal pressures were measured as well, allowing for estimates of transdiaphragmatic pressure (Pdi). In all subjects functional residual capacity at 0 Gz decreased by 244 +/- 31 ml as a result of the inward displacement of the abdomen. End-expiratory Pga decreased from 6.8 +/- 0.8 cmH2O at 1 Gz to 2.5 +/- 0.3 cmH2O at Gz (P less than 0.005). Abdominal contribution to tidal volume increased from 0.33 +/- 0.05 to 0.51 +/- 0.04 at 0 Gz (P less than 0.001) but delta Pga showed no consistent change. Hence abdominal compliance increased from 43 +/- 9 to 70 +/- 10 ml/cmH2O (P less than 0.05). There was no consistent effect of Gz on tidal swings of Pdi, on pulmonary resistance and dynamic compliance, or on any of the timing parameters determining the temporal pattern of breathing. The results indicate that at 0 G respiratory mechanics are intermediate between those in the upright and supine postures at 1 G. In addition, analysis of end expiratory pressures suggests that during weightlessness intra-abdominal pressure is zero, the diaphragm is passively tensed, and a residual small pleural pressure gradient may be present. PMID- 1761498 TI - Parenchymal stress affects interstitial and pleural pressures in in situ lung. AB - After resecting the intercostal muscles and thinning the endothoracic fascia, we micropunctured the lung tissue through the intact pleural space at functional residual capacity (FRC) and at volumes above FRC to evaluate the effect of increasing parenchymal stresses on pulmonary interstitial pressure (Pip). Pip was measured at a depth of approximately 230 microns from the pleural surface, at 50% lung height, in 12 anesthetized paralyzed rabbits oxygenated via a tracheal tube with 50% humidified O2. Pip was -10 +/- 1.5 cmH2O at FRC. At alveolar pressure of 5 and 10 cmH2O, lung volume increased by 8.5 and 19 ml and Pip decreased to -12.4 +/- 1.6 and -12.3 +/- 5 cmH2O, respectively. For the same lung volumes held by decreasing pleural surface pressure to about -5 and -8.5 cmH2O, Pip decreased to 17.4 +/- 1.6 and -23.8 +/- 5 cmH2O, respectively. Because Pip is more negative than pleural pressure, the data suggest that in intact pulmonary interstitium the pressure of the liquid phase is primarily set by the mechanisms controlling interstitial fluid turnover. PMID- 1761499 TI - Tissue temperature profile in the human forearm during thermal stress at thermal stability. AB - The purpose of the present study was to investigate the effect of a range of water temperatures (Tw from 15 to 36 degrees C) on the tissue temperature profile of the resting human forearm at thermal stability. Tissue temperature (Tti) was continuously monitored by a calibrated multicouple probe during 3 h of immersion of the forearm. The probe was implanted approximately 9 cm distal from the olecranon process along the ulnar ridge. Tti was measured every 5 mm, from the longitudinal axis of the forearm (determined from computed tomography scanning) to the skin surface. Along with Tti, skin temperature (Tsk), rectal temperature (Tre), and blood flow were measured during the immersions. For all temperature conditions, the temperature profile inside the limb was linear as a function of the radial distance from the forearm axis (P less than 0.001). Temperature gradient measured in the forearm ranged from 0.2 +/- 0.1 degrees C C cm (Tw = 36 degrees C) to 2.3 +/- 0.5 degrees C cm (Tw = 15 degrees C). The maximal Tti was measured in all cases at the longitudinal axis of the forearm and was in all experimental conditions lower than Tre. On immersion at Tw less than 36 degrees C, the whole forearm can be considered to be part of the shell of the body. With these experimental data, mathematical equations were developed to predict, with an accuracy of at least 0.6 degrees C, the Tti at any depth inside the forearm at steady state during thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761500 TI - TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis. AB - We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies. Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls). Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study. Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study. Animals given TNF had early (0-4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%). In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema. In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days. Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2. In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock. The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury. Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock. PMID- 1761501 TI - Pulmonary hypertension after postlavage lung injury in rabbits: possible role of polymorphonuclear leukocytes. AB - Previous studies showed that repeated lung lavage leads to a severe lung injury with very poor gas exchange, a substantial protein leak into the alveoli with hyaline membrane formation, pulmonary hypertension, and migration of granulocytes (PMN) into the alveolar spaces. Depletion of PMN leads to a better gas exchange and a markedly decreased protein leak with only scanty hyaline membranes. In this study we show that there is sustained pulmonary hypertension after the lung lavage, but in PMN-depleted rabbits there is no postlavage increase in pulmonary arterial pressure. Changing the shunt fraction by manipulating mean airway pressure still leads to a hypoxic vasoconstriction with increase of pulmonary arterial pressure. Thus, after lung lavage, pulmonary reactivity to hypoxia is still preserved. Comparisons between high-frequency ventilation and conventional mechanical ventilation at the same mean airway pressures showed that equal mean airway pressure in these two very different modes of ventilation do not translate into the same mean functional lung volumes. PMID- 1761502 TI - In vivo neutrophil sequestration within lungs of humans is determined by in vitro "filterability". AB - Neutrophils are normally delayed in transit through the lung microcirculation, relative to the passage of erythrocytes. This sequestration contributes to a pulmonary pool of neutrophils that may relate to the relative inability of neutrophils to deform compared with erythrocytes when in transit in the pulmonary capillaries. A micropore membrane was used to model the human pulmonary microcirculation, in which cell deformability was measured as the pressure developed during filtration of the cells through the membrane at a constant flow. We demonstrated a significant correlation between in vitro deformability and in vivo lung sequestration of indium-111-labeled neutrophils in 10 normal subjects (r = 0.69, P less than 0.02). In eight patients with stable chronic obstructive pulmonary disease, this relationship was not significant (r = -0.2, P greater than 0.05). Furthermore, in a subject with microscopic pulmonary telangiectasia known to allow significant passage of 30-microns microspheres, neutrophils passed through the lungs without delay. Moreover, neutrophils from patients studied acutely with an exacerbation of chronic obstructive pulmonary disease were temporarily less deformable (P less than 0.01). These studies confirm that cell deformability is an important determinant of the normal neutrophil sequestration within the lungs. Changes in cell deformability may alter the extent of this sequestration. PMID- 1761503 TI - Effects of gender, age, and fitness level on response of VO2max to training in 60 71 yr olds. AB - The adaptive response of maximal aerobic power (VO2max) to endurance exercise training was compared in 53 men and 57 women, aged 60-71 yr. The subjects were healthy and had been sedentary for at least 2 yr. Pretraining VO2max was measured during graded treadmill walking on two occasions. These values were reproducible (24.4 +/- 4.7 vs. 24.4 +/- 4.6 (SD) ml.min-l.kg-1; r = 0.96). Subjects trained primarily by walking and running for 9-12 mo, averaging 3.9 +/- 0.6 days/wk and 45 +/- 5 min/day at 80 +/- 5% of maximal heart rate (HRmax). Average improvement in VO2max (ml.min-1.kg-1) was 24 +/- 12% (range 0-58%). Relative improvement was not significantly different in men and women (26 +/- 12 vs. 23 +/- 12%, ml.min 1.kg-1; 21 +/- 10 vs 19 +/- 10%, l/min). When subjects were divided into three groups by age (60-62, 63-66, 67-71 yr), there were no significant differences among the groups in the relative increase in VO2max (21% vs. 19% vs. 18%, 1/min). Correlation analysis also yielded a nonsignificant relationship between improvement and age (r = -0.13). To examine the effect of initial fitness level on the adaptive response to exercise, pretraining VO2max was correlated with the absolute improvement in VO2max. This relationship was not significant in either men (r = 0.04) or women (r = -0.23). In conclusion, in healthy people aged 60-71 yr, VO2max adapts to endurance exercise training to the same relative extent as in young people, and this adaptation is independent of gender, age, and initial level of fitness. PMID- 1761504 TI - Analysis of responses to sarafotoxin 6a and sarafotoxin 6c in the pulmonary vascular bed of the cat. AB - Pulmonary vascular responses to sarafotoxins 6a and 6c (S6a and S6c) were investigated in the intact-chest cat under constant flow conditions. Injections of S6a and S6c into the perfused lobar artery caused dose-related increases in lobar arterial pressure, increased left atrial pressure, and produced biphasic changes in systemic arterial (aortic) pressure. When left atrial pressure was maintained constant, injections of S6a, S6c, and endothelin 1 (ET-1) caused dose related increases in lobar arterial pressure. The increases in lobar arterial pressure in response to S6a and S6c were not altered by treatment with a cyclooxygenase inhibitor or a thromboxane receptor blocking agent. Increases in lobar arterial pressure in response to S6a and S6c were not altered when airflow to the left lower lung lobe was interrupted by bronchial occlusion, and pressor responses were not diminished when the left lower lobe was perfused with low molecular-weight dextran. Under conditions of controlled blood flow and constant left atrial pressure, S6a, S6b, S6c, and ET-1 had similar pressor activity, whereas the thromboxane A2 mimic, U-46619, had far greater activity when compared on a nanomolar basis. The present studies demonstrate that S6a and S6c have significant vasoconstrictor activity in the feline pulmonary vascular bed. These data suggest that pulmonary vasoconstrictor responses to the endothelin peptides are not dependent on release of cyclooxygenase products and the activation of thromboxane A2 receptors, alterations in bronchomotor tone, or interaction with formed elements in blood. PMID- 1761505 TI - Multiple muscarinic receptor subtypes in the canine pulmonary circulation. AB - The vascular response to the muscarinic receptor agonist acetylcholine (ACh) in the presence of selected antagonists was examined in the isolated blood-perfused canine left lower lung lobe under conditions of normal (resting) and elevated vascular tone. At normal vascular tone, ACh (1-5 mumol) produced a dose-dependent increase in pulmonary arterial pressure (Ppa), total pulmonary vascular resistance (PVR), and downstream resistance (Rds) without altering upstream resistance (Rus). Pirenzepine (50 and 100 nM), the prototype M1-selective antagonist, and gallamine, an M2-selective antagonist, as well as atropine (50 nM) and secoverine (100 nM), nonselective antagonists, attenuated (P less than 0.05) the ACh-induced increase in Ppa and Rds. With elevated vascular tone induced by serotonin infusion, ACh produced a dose-dependent increase in Ppa in 19 of 25 lobes, although Rus decreased while Rds increased in all lobes. At high vascular tone, pirenzepine or gallamine attenuated the ACh-induced increase in Rds, whereas Rus was not affected. Secoverine and atropine antagonized ACh induced increases in both Rds and Rus. The pA2 values (i.e., the negative log antagonist concentration requiring a doubling of ACh dose for an equivalent increase in Rds) for gallamine, pirenzepine, secoverine, and atropine were 6.1 +/ 0.1, 7.4 +/- 0.1, 8.3 +/- 0.2, and 10.2 +/- 0.3, respectively. These results suggest that 1) ACh increases PVR in the dog by constricting the venous segments (downstream) of the pulmonary circulation via activation of pulmonary vascular muscarinic receptors under conditions of both normal and elevated vascular tone, 2) both M1- and non-M1-muscarinic receptor subtypes appear to participate in mediating the ACh-induced increase in Rds, and 3) ACh moderately relaxes the upstream (arterial) vessels, especially under conditions of elevated tone. PMID- 1761506 TI - Adequacy of a systems structure in the modeling of training effects on performance. AB - A systems model of training effects on performance was applied to eight initially untrained subjects who were volunteers for an endurance training program for the purpose of verifying the statistical adequacy of the systems structure. In the model initially proposed by T. W. Calvert, E. W. Banister, M. V. Savage, and T. Bach (IEEE Trans. Syst. Man Cybern. 6: 94-102, 1976), the performance changes were related to the successive training loads by three first-order transfer functions. In the present study, the number of first-order components was statistically tested. A model including only one component, which had a positive effect on the performance, provided a significant fit with the performances in every subject. A second component significantly improved the fit in only two subjects. This further component, which had a negative effect on performance, was identified as fatigue. Nevertheless, a two-antagonistic component model is proposed to provide a good representation of the training responses. However, the low level of exercise demands and the inaccuracy of the fit could have impaired the evidencing of a fatiguing effect during the presently studied training protocol. PMID- 1761507 TI - An algorithm for angiographic estimation of blood vessel diameter. AB - This study was carried out in an attempt to develop an objective and robust method for measuring changes in the diameters of small blood vessels from X-ray angiographic images. Recognizing potential problems with edge detection methods applied to cylindrical vessels in which the contrast diminishes as the boundary is approached, we have attempted to utilize the X-ray absorbance data across the entire cross section of the vessel. Then, assuming a cylindrical geometry, the absorbance data are fit to the cylindrical absorbance function by use of nonlinear regression analysis. The method was tested and calibrated using glass tubes filled with various concentrations of contrast medium. The diameters of small pulmonary arteries were estimated by applying the method of angiograms obtained from an isolated dog lung lobe. The structure of the residuals obtained after the fitting procedure was analyzed to test the appropriateness of the model for use with images of vessels. The results suggest that this approach will have utility for systematically quantifying vessel dimensions. PMID- 1761508 TI - Use of 13C substrates for metabolic studies in exercise: methodological considerations. PMID- 1761509 TI - Augmentation of prostaglandin E2 production by mammalian phospholipase A2 added exogenously. AB - Rat group II phospholipase A2 added exogenously to A23187-activated HL-60 granulocytes augmented their production of prostaglandin E2. Human group II phospholipase A2 and porcine group I phospholipase A2 augmented the prostaglandin E2 production in a similar manner. No significant increase in prostaglandin E2 production was observed when cells were treated with purified phospholipase A2 in the absence of A23187. Extracellular phospholipase A2 at inflamed sites may contribute to the generation of pro-inflammatory lipid mediators by hydrolyzing the cellular phospholipids of activated inflammatory cells. PMID- 1761510 TI - A continuous cell-free protein synthesis system for coupled transcription translation. AB - A continuous cell-free protein synthesis system [Spirin et al. (1988) Science 242, 1162-1164] was modified so as to be suitable for coupled transcription translation, a process useful for obtaining products of cloned genes or cDNAs. A reaction chamber equipped with an ultrafiltration membrane was newly designed and an HPLC pump was used to supply a low molecular weight substrate solution at a constant rate to the viscous reaction mixture in the chamber. By using an Escherichia coli S30 extract in this modified flow system (1 ml), coupled transcription-translation could be continuously performed for 17 h, the synthesized chloramphenicol acetyltransferase (congruent to 0.1 mg) being subsequently eluted through the chamber's membrane and then purified. PMID- 1761511 TI - A resonance Raman study on a reaction intermediate of Pseudomonas L-phenylalanine oxidase (deaminating and decarboxylating). AB - Resonance Raman (RR) spectra of purple intermediates of L-phenylalanine oxidase (PAO) with non-labeled and isotopically labeled phenylalanines as substrates, i.e., [1-13C], [2-13C], [ring-U-13C6], and [15N]phenylalanines, were measured with excitation at 632.8 nm within the broad absorption band around 540 nm. The spectra obtained resemble those of purple intermediates of D-amino acid oxidase (DAO). The isotope effects on the 1,665 cm-1 band with [15N] or [2 13C]phenylalanine indicate that the band is due to the C = N stretching mode of an imino acid derived from phenylalanine, i.e., alpha-imino-beta phenylpropionate. The intense band at 1,389 cm-1 is contributed to by the CO2- symmetric stretching and C-CO2- stretching modes of alpha-imino-beta phenylpropionate. The 1,602 cm-1 band, which does not shift upon isotopic substitution of phenylalanine, corresponds to the 1,605 cm-1 band of DAO purple intermediates and was assigned to a vibrational mode associated with the C(10a) = C(4a) - C(4) = O moiety of reduced flavin. These results confirm that PAO purple intermediates consist of the reduced enzyme and an imino acid derived from a substrate, and suggest that the plane defined by C(10a) = C(4a) - C(4) = O of reduced flavin and the plane containing H2+N = C - CO2- of an imino acid are arranged in close contact to each other, generating a charge-transfer interaction. PMID- 1761512 TI - Ornithine decarboxylase induction in partially hepatectomized rat liver and modes of its stimulation by glucagon and insulin. AB - Hepatic ornithine decarboxylase (ODC) activity increases after partial hepatectomy and this activity is further stimulated by pharmacologic doses of glucagon and insulin. We now present data suggesting that glucagon and insulin stimulate ODC activity by distinct mechanisms. ODC activity increased progressively after partial hepatectomy and reached an initial peak at 4 h. Activity decreased to 50% of its peak value at 6 and 8 h and then rose progressively to a maximum at 12 h. Enzymatic activity was well correlated with the amount of hepatic immunoreactive ODC protein, thus suggesting that increased enzyme activity was due to increased amount of enzyme protein. Hepatic ODC mRNA increased gradually and continuously, reaching the maximal value by 12 h. In rats receiving glucagon after partial hepatectomy, ODC mRNA increased significantly by 2 h and enzyme immunoreactive protein and activity by 2 to 4 h as compared to controls. In contrast, insulin administration only induced a significant increase in enzyme immunoreactive protein and activity 10 to 12 h after partial hepatectomy. No significant changes in ODC mRNA level were observed. Our data suggest that the regulation mechanism of ODC induction following partial hepatectomy differs depending on the time after operation. Our data also suggest that while glucagon appears to regulate ODC activity by a transcriptional mechanism, insulin appears to operate at a post-transcriptional level. PMID- 1761513 TI - Multiple proteolytic action of rat liver cathepsin B: specificities and pH dependences of the endo- and exopeptidase activities. AB - Dipeptidylcarboxypeptidase, endopeptidase, and carboxypeptidase activities of rat liver cathepsin B were investigated using soluble denatured protein substrates, reduced and S-(3-trimethylammonio)propylated proteins and their derivatives. It was found that the soluble denatured proteins were degraded mainly by the dipeptidylcarboxypeptidase activity and in a few cases by the endopeptidase and carboxypeptidase activities. The eipeptidylcarboxypeptidase activity showed broad substrate specificity with broad pH optimum at 4-6. A peptide having the alpha carboxyl group amidated with methylamine could also be a good substrate for this activity. These results suggest that this activity is dependent not upon the dissociated alpha-carboxyl group at the P2' site but upon the hydrogen-bonding abilities of the alpha-imino moiety and the protonated or amidated alpha-carboxyl moiety at P2'. On the other hand, the endopeptidase and carboxypeptidase activities were observed in a few cases, suggesting that special amino acid sequences in the substrates are responsible for these activities. These activities showed sharp pH optima at 6 and seemed to prefer basic amino acid residues at P1 site. Therefore, we suppose that cathepsin B has a carboxyl group with a pKa of about 5.5 at the S1 subsite which more effectively interacts with a positive charge at the P1 site of the substrate at pH 6 than at pH 5. Based on these results, a model of the binding subsites of this enzyme is proposed. PMID- 1761514 TI - Composition of long chain bases in ceramide of the guinea pig Harderian gland. AB - Ceramide of the guinea pig Harderian gland was isolated and characterized. The purified ceramide gave two spots on thin-layer chromatography. Ceramide with the higher Rf value (NHCer) contained non-hydroxy fatty acids and that with the lower Rf value (HCer) contained 2-hydroxy fatty acids. The ratio of NHCer to HCer was 6:1. The non-hydroxy fatty acids of NHCer were composed of straight-chain acids (94.9%) and branched-chain acids (5.1%). The 2-hydroxy fatty acids were also composed of straight-chain acids (94.2%) and branched-chain acids (5.8%). The ratio of straight-chain acids to branched-chain acids was similar in NHCer and HCer. The long chain bases of NHCer and HCer consisted of straight chain sphinganines and sphingenines, and methyl-branched long chain bases. In NHCer, 59.9% of the total bases were methyl branched, and in HCer, 48.3%. The characteristics of ceramide, that is, the large amount of methyl-branched long chain bases and relatively small amount of methyl-branched fatty acids, are similar to those of cerebroside and sphingomyelin isolated from the same organ, although the ratios of constituents are different among these sphingolipids. PMID- 1761515 TI - Purification of hepatic N-hydroxyarylamine sulfotransferases and their regulation by growth hormone and thyroid hormone in rats. AB - From liver cytosols of male Sprague-Dawley rats, two N-hydroxyarylamine sulfotransferases (HASTs) which sulfate N-hydroxy-2-acetylaminofluorene and a phenolsulfotransferase (PST-I) have been purified about 290-, 690-, and 210-fold, respectively, by the use of DEAE-anion exchange, Blue-Sepharose CL-6B, DEAE-HPLC, and ATP-agarose affinity chromatography. All three enzymes showed almost the same molecular weight of 33 kDa on SDS-polyacrylamide gel electrophoresis. In Western blots using antibody raised against HAST I, the two HASTs, but not PST-I, were detected. The content of total HAST in male rats was estimated as 4-5 micrograms/mg cytosolic protein, about 4 times higher than that in female rats. Direct comparison of the DEAE-HPLC elution profiles of cytosol showed that HAST I and HAST II were male-dominant and male-specific, respectively, in their expression in the livers. Hypophysectomy decreased the level of HAST by 60% in male rats, but had no obvious effect in female rats. Intermittent injection of growth hormone to mimic the male secretory pattern raised the content in hypophysectomized rats of both sexes close to that in intact male rats, while the continuous infusion of growth hormone to mimic the female secretory pattern showed limited effects. In addition, the administration of triiodothyronine stimulated HAST in hypophysectomized rats of both sexes, and the extent of stimulation was nearly the same as observed in the male-type growth hormone treatment. PST-I, in contrast to HAST, showed no clear sex-related difference in hepatic content, and was not apparently affected by growth hormone or triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761516 TI - Xenobiotic responsive element in the 5'-upstream region of the human P-450c gene. AB - The nucleotide sequence of the 5'-upstream region up to about -4.1 kb of the human P-450c gene was determined. Two kinds of repetitive sequences were located; one was the Alu sequence which was inserted at three positions (-3127 to -3038, 3017 to -2770, and -2167 to -1851), and the other was the SINE-R element located just upstream of the most distal Alu sequences. The region other than the two repeated sequences showed an overall similarity of 70% to that of the rat P-450c gene. Survey of XRE or its homologues, responsible for the inducible expression of the rat P-450c gene, revealed eight XRE core sequences in this region of the human P-450c gene. Three of them were carried in the Alu sequences. A fusion gene which was constructed by ligating the upstream region of the human P-450c gene to the chloramphenicol acetyltransferase (CAT) gene expressed the CAT activity in response to the inducer, methylcholanthrene, when transfected into Hepa-1 cells. Stepwise decrease in CAT activity in three regions was observed as the 5' upstream sequence containing XRE motifs was removed. However, the XRE core sequence in the Alu sequences seemed inactive, because elimination of the three elements in the Alu sequences did not affect the expressed CAT activity. In accordance with this observation, competition experiments using gel mobility shift assay showed that XRE core sequences in the Alu sequences could not compete with the XRE sequence for the inducer-bound receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761517 TI - The existence of galactosylceramide I3-sulfate in serums of various mammals and its anticoagulant activity. AB - Human, porcine, goat, sheep, bovine, horse, canine, rat, mouse, guinea pig, and chicken serums were investigated for the existence of sulfatide. Among the ten mammal serums, seven were found to be sulfatide positive, and the amounts of sulfatide were determined to be: 16.29 nmol/ml serum (porcine), 9.39 (bovine), 12.71 (goat), 7.75 (horse), 1.21 (sheep), 0.64 (human), and 0.16 (dog). The existence of sulfatide in the serums of human, goat, sheep, cow, horse, and dog is here reported for the first time. It is suggested that sulfatide is widely distributed in the serums of various mammals except for rodents and that it takes part in the anticoagulant systems. The fatty acids of those sulfatides comprised mainly non-hydroxy fatty acids and a significant amount (18-53% of the total fatty acid) of hydroxy fatty acids with chain lengths of C16, C22, C23, and C24. The long chain bases comprised sphingenine, sphinganine, and 4-D hydroxysphinganine. Experiments to elucidate the mechanism of the anticoagulant activity of sulfatide revealed that it was specific to sulfatide and that the galactose-bound sulfate group is essential for this activity. The activity of clusters of sulfatide molecules was much more pronounced than that of single molecules. PMID- 1761518 TI - Ribulose bisphosphate-induced, slow conformational changes of spinach ribulose bisphosphate carboxylase cause the two types of inflections in the course of its carboxylase reaction. AB - The cause of the inflection in the course of the carboxylase reaction and the changes in the functioning form of spinach ribulose bisphosphate carboxylase (RuBisCO) during the reaction were elucidated by relating the activity to the protein conformation of RuBisCO using a fluorescence probe, 2-p toluidinylnaphthalene sulfonate. The activity of RuBisCO in the linear phase was 50 to 60% of that in the initial burst at 0.5 to 1.0 mM ribulose bisphosphate (RuBP) and 65 to 80% at 2 to 5 mM RuBP. The amount and the progress of the decrease in the activity during the reaction had a close relationship to a change in the protein conformation of RuBisCO. The enzyme, the substrate binding sites of which were masked beforehand with carboxyarabinitol bisphosphate, still showed a change of its protein conformation upon addition of RuBP, suggesting that RuBisCO has two (substrate and regulatory) RuBP-binding sites per RuBisCO promoter. RuBisCO required over 2 mM RuBP for binding on the regulatory sites. Both sites also bound 6-phosphogluconate. When both sites were masked with 6 phosphogluconate beforehand, the course of the subsequent carboxylase reaction was linear with time. From these results, I propose that the inflection in the course of the reaction of spinach RuBisCO is a hysteretic response of the enzyme to RuBP bound to both substrate and regulatory sites. PMID- 1761519 TI - Cooperative binding of carboxyarabinitol bisphosphate to the regulatory sites of ribulose bisphosphate carboxylase/oxygenase from spinach. AB - Ribulose bisphosphate carboxylase (RuBisCO) binds carboxyarabinitol bisphosphate (CABP) on its regulatory sites [Yokota, A. (1991) J. Biochem. 110, 246-252]. The characteristics of the equilibrium binding of CABP to the sites were examined by the gel-filtration method. Since RuBisCO binds CABP on the substrate sites with a dissociation constant of less than 10 pM, CABP bound exclusively to the substrate sites at less than 5 microM. Plotting the number of CABP bound to the sites other than the substrate sites against the concentration of CABP gave a typical "bumpy" curve; the binding number in the intermediate plateau at 20 to 40 microM CABP was 3.7 to 4.4 mol per mol of RuBisCO and that at the saturating concentration of CABP was 7.6 to 7.8 mol per mol of RuBisCO. The Hill plot of their relationship gave a line which bent strongly at 20 to 40 microM CABP. The best fitting of the data to the equations derived from the binding model constructed according to the reported model [Teipel, J. & Koshland, D.E., Jr. (1969) Biochemistry 8, 4656 4663] showed that the binding of CABP to the regulatory sites proceeded with positive cooperativity both before and after the plateau. The dissociation constant decreased from 31 to 14 microM by the factor of 1/1.3 in the former group and 490 to 0.7 microM by the factor of 1/8.9 in the latter with increasing binding number of CABP. PMID- 1761520 TI - Mechanisms of stimulation of collagen synthesis during chick embryonic skin development. AB - To study how collagen synthesis is regulated in developing chick embryonic skin, hydroxyproline synthesis, incorporation of proline, and translational activity and content of collagen mRNA in 12-, 15-, and 18-day skins were determined and compared with each other. Hydroxyproline synthesis in the 18-day skins was markedly increased over that in the 12-day skins, whereas proline incorporation was moderately increased. The increase in collagen synthesis from day 15 to 18 was accompanied by increases in both the translational activity and the content of type I procollagen mRNA, with a selective increase in the lower-molecular weight species of pro alpha 1 (I) collagen mRNA. In contrast, the stimulation of collagen synthesis from day 12 to day 15 did not parallel the levels of type I procollagen mRNA. These results suggest that the stimulation of collagen synthesis is regulated by collagen mRNA levels only in the later stage of development (from day 15 to day 18). Both the collagen synthesis and type I procollagen mRNA levels in the fibroblasts isolated on each corresponding day were constant. The difference in collagen synthesis under two different culture conditions suggests that cell-matrix interaction and/or some serum factors, including several growth factors, are essential for the marked stimulation of collagen synthesis observed in 12- to 18-day skin. PMID- 1761521 TI - Identification of a cross-linked peptide of a covalent complex between adrenodoxin reductase and adrenodoxin. AB - A cross-linked complex between bovine NADPH-adrenodoxin reductase (AR) and adrenodoxin (AD) was prepared with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and purified, as described previously [Hara, T. & Kimura, T. (1989) J. Biochem. 105, 594-600]. The covalent complex was S-pyridylethylated and digested with lysylendopeptidase, and the resulting peptides were separated by reversed-phase HPLC to identify the cross-linked peptide. Comparison of the HPLC chromatograms of the peptides showed that (i) two tandem peptides (K-4 and K-5) from AD and a peptide (K-1) from AR were missing in the chromatogram of the peptides of the covalent complex and (ii) a single new peak was observed in the chromatogram of the peptides from the covalent complex. Amino acid composition and sequence analyses showed that the newly observed peptide was a covalently cross-linked peptide formed between a peptide K-4-K-5 (Ile-25-Lys-98) derived from AD and a peptide K-1 (Ser-1-Lys-27) derived from AR, in which an amide bond had been formed between the epsilon-amino group of Lys-66 in AD and the gamma-carboxyl group of Glu-4 in AR. These results indicate that the binding site of AR with AD is localized in the amino-terminal part of AR and that of AD with AR is localized around Lys-66 of AD. The six clustered basic amino acid residues (His-24, Lys-27, His-28, His-29, Arg-31, and His-33) present in the amino-terminal portion of AR and the eight clustered acidic amino acid residues (Glu-65, Glu-68, Asp-72, Glu 73, Glu-74, Asp-76, Asp-79, and Asp-86) present in the middle part of AD may play an important role in the complex formation. PMID- 1761522 TI - A GM1b-derived disialoganglioside GD1c is the predominant ganglioside of rat thymocytes. AB - The thin-layer chromatographic (TLC) pattern of gangliosides of rat thymocytes showed a profile characterized by the occurrence of a predominant ganglioside which did not correspond to any reference gangliosides of rat brain. The ganglioside was isolated from rat thymus, and characterized by compositional analysis, methylation analysis, sialidase treatment, negative-ion fast atom bombardment (FAB) mass spectrometry, and proton NMR spectroscopy. The structure was elucidated to be NeuGc alpha 2-8NeuGc alpha 2-3Gal beta 1-3GalNac beta 1-4Gal beta 1-4Glc beta 1-1Cer. This is the major ganglioside of rat thymus lymphoid cells and is one of the GM1b-derived gangliosides, GD1c, having two N glycolylneuraminic acids. This is the first report on the occurrence of GD1c in normal animal cells. PMID- 1761523 TI - Thermostable alanine racemase of Bacillus stearothermophilus: subunit dissociation and unfolding. AB - The guanidine hydrochloride-induced subunit dissociation and unfolding of thermostable alanine racemase from Bacillus stearothermophilus have been studied by circular dichroism, fluorescence and absorption spectroscopies, and gel filtration. The overall process was found to be reversible: more than 75% of the original activity was recovered upon reduction of the denaturant concentration. In the range of 0.6 to 1.5 M guanidine hydrochloride, the dimeric enzyme was dissociated into a monomeric form, which was catalytically inactive. The monomeric enzyme appeared to bind the cofactor pyridoxal phosphate by a non covalent linkage, although the native dimeric enzyme binds the cofactor through an aldimine Schiff base linkage. The monomer was mostly unfolded, with the transition occurring in the range of 1.8 to 2.2 M guanidine hydrochloride. PMID- 1761524 TI - Production and characterization of functional domains of human fibronectin expressed in Escherichia coli. AB - An efficient expression system was constructed in Escherichia coli that produced a 33-kDa fragment, C-274, of human fibronectin with a strong cell-adhesive activity. The entire sequence of the heparin-binding domain with 271 amino acids, H-271, was also expressed. Deletion analysis of the type III repeats showed that the heparin-binding site was at type III-13. The cell-adhesive activity of a fusion protein, CH-271, containing the cell- and the heparin-binding domains was twice that of C-274 when BHK but not B16-F10 melanoma cells were tested; H-271 alone was inactive. Recombinant proteins containing the CS1 sequence of the IIICS region were more active than C-274 and CH-271 with B16-F10. However, H-296, which contained both H-271 and CS1, was almost inactive with BHK. CH-296, which contained CS1 at the C-terminus of CH-271, was more active with B16-F10 than H 296 and C-CS1, which was produced by the deletion of H-271 from CH-296. Thus, the cell-binding domain was active with both kinds of cells. The heparin-binding domain promoted the adhesion of both kinds of cells only when linked to the cell binding domain or CS1. CS1 was specific for the adhesion of B16-F10 but was not essential. PMID- 1761525 TI - Site-specific 13C-labeling of Trp 62 in hen egg-white lysozyme: preparation and 13C-NMR titration of [delta 1-13C]Trp 62-lysozyme. AB - The indole C-2(delta 1) carbon of Trp 62 in hen egg-white lysozyme was selectively labeled with 13C through a series of reactions involving N' formylkynurenine 62-lysozyme with K13CN, NaBH4-reduction, and acid-catalyzed dehydration. [delta 1-13C]Trp 62-lysozyme in which Trp 62 is labeled with 90% 13C has the same chemical and enzymatic properties as the native protein. The reverted lysozyme gave a single 13C-NMR signal at 125 ppm. pH-titration of the 13C signal indicated a transition at pH 3.9 for the free enzyme. In the presence of (GlcNAc)3, the resonance signals were shifted 0.5-1 ppm upfield, and the transitions in the titration curve were observed at pH 3.9 and 6.5. Asp 52 and Glu 35 were assigned to the groups with pKas of 3.9 and 6.5, respectively. In [2 13C]AHT 62-lysozyme, which has 3-(2-amino-3-hydroxy-3H-[2-13C]indol-3-yl)alanine (AHT) at position 62, AHT 62 behaved quite differently from Trp 62 on pH titration of the 13C-label. These results suggest that a conformational change around Trp 62 is induced upon ionization of the catalytic residue and that the structural flexibility of the side chain of this aromatic residue in the substrate binding site is closely related to the function of lysozyme. PMID- 1761526 TI - Localization of beta-actinin in the Z lines of chicken breast muscle, as detected with a monoclonal antibody specific to the beta I subunit (Cap Z alpha). AB - Immunofluorescence microscopy showed that a monoclonal antibody, 2F3, specific to the beta I subunit (Cap Z alpha) of beta-actinin (Cap Z) bound to the Z lines of chicken breast muscle. When myofibrils were briefly extracted with 0.6 M KI, the reactivity of the Z lines with 2F3 was very weak, but on subsequent treatment with purified beta-actinin, the antibody binding recovered. beta-Actinin inhibited elongation of the actin filaments of isolated I-Z-I brushes, myosin extracted sarcomeres, on the addition of G-actin. However, when an increased concentration of G-actin was added, the inhibitory action of beta-actinin became negligible, suggesting that beta-actinin did not cap the pointed end of an actin filament in a myofibril. PMID- 1761527 TI - Molecular structure of a yeast gene, PDI1, encoding protein disulfide isomerase that is essential for cell growth. AB - A genomic DNA clone for protein disulfide isomerase (PDI) of Saccharomyces cerevisiae was isolated by hybridization with synthesized oligonucleotide probes based on a partial amino acid sequence of yeast PDI. The introduction of a multiple copy plasmid carrying this fragment into yeast caused a tenfold increase in PDI specific activity and in the amount of PDI antigen in the extract. The gene on this fragment was named PDI1. The nucleotide sequence of the gene predicts a polypeptide of 522 amino acids with about 30% identity to mammalian PDIs. The predicted amino acid sequence contains an N-terminal signal peptide like sequence, the C-terminal putative endoplasmic reticulum retention signal of yeast (HDEL), and two putative active site sequences of PDI (WCGHCK). The predicted polypeptide is acidic and contains five putative glycosylation sites, consistent with the molecular properties of the purified yeast PDI [T. Mizunaga et al. (1990) J. Biochem. 108, 846-851]. The PDI1 gene was mapped on chromosome III. A gene disruption experiment revealed that the PDI1 gene is essential for cell growth. PMID- 1761528 TI - Biological role and regulation of the universally conserved heat shock proteins. PMID- 1761529 TI - Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts. AB - A cDNA clone complementary to an interferon (IFN)-induced mRNA was isolated and used to characterize the regulation of expression of its RNA by the IFNs and to identify the protein its RNA encodes. This cDNA hybridizes to IFN-induced 3.1- and 2.3-kilobase mRNAs that are synthesized in response to both IFN-alpha and IFN gamma. IFN-gamma induces the sustained accumulation of these mRNAs while IFN alpha induces their transient accumulation. Cycloheximide (50 micrograms/ml) failed to inhibit the induction of these mRNAs by either IFN-alpha or IFN-gamma, suggesting that their induction does not require de novo protein synthesis. DNA sequence analysis of this cDNA reveals that it encodes a protein of Mr 53,168 that has sequence homology with and the biological activity of a tryptophanyl tRNA synthetase, an enzymatic activity that has been demonstrated to play a role in and be modulated by the growth of cells. Elevated levels of this enzyme may be involved in the cell growth inhibitory activity of the IFNs. PMID- 1761530 TI - Cell attachment activity of the carboxyl-terminal domain of human thrombospondin expressed in Escherichia coli. AB - Thrombospondin (TS) is a multidomain, adhesive glycoprotein that associates with cells through multiple cell attachment sites. One of these has been located in or near the globular COOH-terminal region of TS by the monoclonal antibody (mAb) C6.7, which inhibits the attachment of human melanoma cells (G361) to TS. The epitope for C6.7 lies within the last 122 residues of the COOH-terminal domain of TS. This domain is distant from two known cell attachment sites in TS, namely the NH2-terminal heparin-binding domain and the CSVTCG sequences in the type I repeats, but is close to the RGDA sequence, an integrin-dependent cell attachment site. In order to separate the adhesive activity of the TS COOH-terminal domain from that of the RGD sequence, we have expressed the COOH-terminal 212 amino acids (residues 941-1152) of TS in Escherichia coli using the expression vector pRIT2T. The resultant fusion protein is effective in supporting G361 cell attachment even though it lacks the RGD sequence. In addition, the expressed protein inhibits adhesion of G361 cells to intact TS. mAb C6.7 blocks adhesion to the expressed TS COOH-terminal domain whereas GRGDSP and VTCG peptides are not inhibitory. These results show that the TS COOH-terminal domain contains a separate cell adhesion site, defined by mAb C6.7, that is distinct from the other adhesion sites of TS. PMID- 1761531 TI - Chitin utilization by marine bacteria. A physiological function for bacterial adhesion to immobilized carbohydrates. AB - Chitin turnover is essential for recycling carbon and nitrogen in marine ecosystems. A key step in this process is the adhesion of marine bacteria to chitin-containing particulates. Vibrio species were therefore surveyed for their ability to bind to immobilized carbohydrates, and one, Vibrio furnissii, adhered to glycosides of three sugars, N-acetylglucosamine (the preferred ligand), D mannose, and D-glucose. A single Ca(2+)-requiring lectin is responsible for binding to the three sugars. Cells adhering to the chitin analogue divided at the same rate as cells in liquid culture. The first progeny of adherent cells continued to bind to the beads, but the population gradually shifted to a large fraction of free swimming cells, a process that may be necessary for colonization. Metabolic energy is required for cell adhesion to the glycosides, and transient (or no) adhesion occurred in incomplete growth media. The results were explained by studying met and pro mutants. Both the initiation and maintenance of lectin-mediated adhesion requires continuous protein synthesis; expression of lectin activity is a major priority of these cells and functions under conditions adequate for minimal protein synthesis, but insufficient to support cell growth. The adhesion/deadhesion apparatus is apparently used to continuously monitor the nutrient status of the environment, i.e. as a nutrient sensorium. In incomplete medium, cells deadhere, presumably to migrate to a more favorable environment. PMID- 1761532 TI - Chitin utilization by marine bacteria. Chemotaxis to chitin oligosaccharides by Vibrio furnissii. AB - The adhesion/deadhesion apparatus of the marine bacterium Vibrio furnissii (Yu, C., Lee, A., Bassler, B. L., and Roseman, S. (1991) J. Biol. Chem. 266, 24260 24267) probably catalyzes the first step in colonizing chitin. Evidence is presented here for a second step, chemotaxis to chitin hydrolysis products. V. furnissii swarms toward chitin oligomers (GlcNAc)n, n = 1-6, at initial concentrations as low as 10 microM. A modified capillary assay was used for quantitation; the cells exhibit low level constitutive taxis to GlcNAc but not to the oligosaccharides. A mutant defective in the GlcNAc receptor (IINag of the phosphotransferase system) showed inducible taxis to the oligosaccharides. Two (or more) independently inducible receptors with overlapping specificities recognize (GlcNAc)n, n = 2-4. (GlcNAc)5 and (GlcNAc)6 were inactive in the capillary assay; expression of this receptor(s) apparently require special induction conditions. The (GlcNAc)n, n = 1-4, chemoreceptors of V. furnissii may be the most potent reported for bacteria. L-Amino acids were weak, constitutive attractants; glutamine, not known to be an attractant in other bacteria, was the most effective amino acid. The most potent receptor in Escherichia coli, Tar (aspartate), is not expressed in V. furnissii. The chemotactic responses were greatly affected by growth and induction conditions and the presence of nutrients in the assay media. Taxis to GlcNAc and GlcNAc oligomers was optimally induced by growth in lactate medium containing 0.6 mM sugar, while growth on the sugar per se resulted in poor taxis. Chemotaxis to the sugars increased 2- to 3-fold when the cells were starved. Nutrients in the assay medium, especially compounds that feed into or are part of the Krebs cycle, were potent inhibitors of taxis to the sugars and Gln. With the exception of isocitrate, inhibition of taxis correlated with the rate of oxidation of these compounds. The results suggest a link between catabolism and taxis in this organism, i.e. interactions or "cross-talk" between systems that are regulated by protein phosphorylation (Stock, J. A., Ninfa, A. J., and Stock, A. M. (1989) Microbiol. Rev. 53, 450-490). PMID- 1761533 TI - Chitin utilization by marine bacteria. Degradation and catabolism of chitin oligosaccharides by Vibrio furnissii. AB - Chemotaxis of the marine bacterium Vibrio furnissii to chitin oligosaccharides has been described (Bassler, B. L., Gibbons, P. J., Yu, C., and Roseman, S. (1991) J. Biol. Chem. 266, 24268-24275). Some steps in catabolism of the oligosaccharides are reported here. GlcNAc, (GlcNAc)2, and (GlcNAc)3 are very rapidly consumed by intact cells, about 320 nmol of GlcNAc equivalents/min/mg of protein. (GlcNAc)4 is utilized somewhat more slowly. During these processes, there is virtually no release of hydrolysis products by the cells. The oligosaccharides enter the periplasmic space (via specific porins?) and are hydrolyzed by a unique membrane-bound endoenzyme (chitodextrinase) and an exoenzyme (N-acetyl-beta-glucosaminidase; beta-Glc-NAcidase). The genes encoding these enzymes have been cloned and expressed in Escherichia coli. The chitodextrinase cleaves soluble oligomers, but not chitin, to the di- and trisaccharides, while the periplasmic beta-GlcNAcidase hydrolyzes the GlcNAc termini from the oligomers. The end products in the periplasm, GlcNAc and (GlcNAc)2 (possibly (GlcNAc)3) are catabolized as follows. (a) Disaccharide pathway, A (GlcNAc)2 permease is apparently expressed by Vibrio furnissii. Translocated (GlcNAc)2 is rapidly hydrolyzed by a soluble, cytosolic beta GlcNAcidase, and the GlcNAc is phosphorylated by an ATP-dependent, constitutive kinase to GlcNAc-6-P. (b) Monosaccharide pathway, Periplasmic GlcNAc is taken up by Enzyme IINag of the phosphoenolpyruvate:glycose phosphotransferase system, yielding GlcNAc-6-P, the common intermediate for both pathways. Finally, GlcNAc-6 P----Ac- + GlcNH2-6-P----Fru-6-P + NH3. (GlcNAc)2 is probably the "true" inducer of the chitin degradative enzymes described in this report and, depending on its concentration in the growth medium, differentially induces the periplasmic and cytosolic beta-GlcNAcidases. The disaccharide pathway appears to be the most important when the cells are confronted with low concentrations of the oligomers (e.g. in chemotaxis swarm plates). The relative activities of the induced enzymes suggest that the rate-limiting steps in oligosaccharide catabolism are the glycosidase activities in the periplasm. PMID- 1761534 TI - Proline residues responsible for thermostability occur with high frequency in the loop regions of an extremely thermostable oligo-1,6-glucosidase from Bacillus thermoglucosidasius KP1006. AB - The gene encoding for an extremely thermostable oligo-1,6-glucosidase from Bacillus thermoglucosidasius KP1006 (DSM2542, obligate thermophile) was sequenced. The amino acid sequence deduced from the nucleotide sequence of the gene (1686 base pairs) corresponded to a protein of 562 amino acid residues with a Mr of 66,502. Its predicted amino acid composition, Mr, and N-terminal sequence of 12 residues were consistent with those determined for B. thermoglucosidasius oligo-1,6-glucosidase. The deduced sequence of the enzyme was 72% homologous to that of a thermolabile oligo-1,6-glucosidase (558 residues) from Bacillus cereus ATCC7064 (mesophile). B. cereus oligo-1,6-glucosidase contained 19 prolines. Eighteen of these were conserved at the equivalent positions of B. thermoglucosidasius oligo-1,6-glucosidase. This enzyme contained 14 extra prolines besides the conservative prolines. The majority of extra prolines was replaced by polar or charged residues (Glu, Thr, or Lys) in B. cereus oligo-1,6 glucosidase. The extra prolines were responsible for the difference in thermostability between these two enzymes. We suggested that 11 of the extra prolines in B. thermoglucosidasius oligo-1,6-glucosidase occur in beta-turns or in coils within the loops binding adjacent secondary structures. PMID- 1761535 TI - Identification of the essential cysteine residue in Klebsiella aerogenes urease. AB - During reaction with [14C]iodoacetamide at pH 6.3, radioactivity was incorporated primarily into a single Klebsiella aerogenes urease peptide concomitant with activity loss. This peptide was protected from modification at pH 6.3 by inclusion of phosphate, a competitive inhibitor of urease, which also protected the enzyme from inactivation. At pH 8.5, several peptides were alkylated; however, modification of one peptide, identical to that modified at pH 6.3, paralleled activity loss. The N-terminal amino acid sequence and composition of the peptide containing the essential thiol was determined. Previous enzyme inactivation studies of K. aerogenes urease could not distinguish whether one or two essential thiols were present per active site (Todd, M. J., and Hausinger, R. P. (1991) J. Biol. Chem. 266, 10260-10267); we conclude that there is a single essential thiol present and identify this residue as Cys319 in the large subunit of the heteropolymeric enzyme. PMID- 1761536 TI - Effects of MgATP, MgADP, and Pi on actin movement by smooth muscle myosin. AB - To test the idea that the in vitro motility assay is a simplified model system for muscle contraction, the MgATP-dependent movement of actin filaments by thiophosphorylated smooth muscle myosin was characterized in the presence of the products MgADP and inorganic phosphate. The dependence of actin filament velocity on MgATP concentration was hyperbolic with a maximum velocity of 0.6 micron/s and an apparent Km = 40 microM (30 degrees C). MgADP competitively inhibited actin movement by MgATP with a Ki = 0.25 mM. Inorganic phosphate did not affect actin filament velocity in the presence of 1 mM MgATP, but competitively inhibited movement in the presence of 50 microM MgATP with a Ki = 9.5 mM. The effects of ADP and Pi on velocity agree with fiber mechanical studies, confirming that the motility assay is an excellent system to investigate the molecular mechanisms of force generation and shortening in smooth muscle. The rate at which rigor cross bridges can be recruited to move actin filaments was observed by initiating cross bridge cycling from rigor by flash photolysis of caged MgATP. Following the flash, which results in a rapid increase in MgATP concentration, actin filaments experienced a MgATP-dependent delay prior to achieving steady state velocity. The delay at low MgATP concentrations was interpreted as evidence that motion generating cross-bridges are slowed by a load due to a transiently high percentage of rigor cross-bridges immediately following MgATP release. PMID- 1761537 TI - Thermodynamics of the binding of galactopyranoside derivatives to the basic lectin from winged bean (Psophocarpus tetrogonolobus). AB - The thermodynamics of the binding of D-galactopyranoside (Gal), 2-acetamido-2 deoxygalactopyranoside (GalNAc), methyl-alpha-D-galactopyranoside, and methyl beta-D-galactopyranoside to the basic agglutinin from winged bean (WBAI) in 0.02 M sodium phosphate and 0.15 M sodium chloride buffer have been investigated from 298.15 to 333.15 K by titration calorimetry and at the denaturation temperature by differential scanning calorimetry (DSC). WBAI is a dimer with two binding sites. The titration calorimetry yielded single-site binding constants ranging from 0.56 +/- 0.14 x 10(3) M-1 for Gal at 323.15 K to 7.2 +/- 0.5 x 10(3) M-1 for GalNAc at 298.15 K and binding enthalpies ranging from -28.0 +/- 2.0 kJ mol-1 for GalNAc at 298.15 K to -14.3 +/- 0.1 kJ mol-1 for methyl-beta-D-galactopyranoside at 322.65 K. The denaturation transition consisted of two overlapping peaks over the pH range 5.6-7.4. Fits of the differential scanning calorimetry data to a two state transition model showed that the low temperature transition (341.6 +/- 0.4 K at pH 7.4) consisted of two domains unfolding as a single entity while the higher temperature transition (347.8 +/- 0.6 K at pH 7.4) is of the remaining WBAI dimer unfolding into two monomers. Both transitions shift to higher temperatures and higher calorimetric enthalpies with increase in added ligand concentration at pH 7.4. Analysis of the temperature increase as a function of added ligand concentration suggests that one ligand binds to the two domains unfolding at 341.6 +/- 0.6 K and one ligand binds to the domain unfolding at 347.8 +/- 0.6 K. PMID- 1761538 TI - Kinetic studies of human immunodeficiency virus type 1 protease and its active site hydrogen bond mutant A28S. AB - Human immunodeficiency virus type 1 (HIV-1) protease optimally catalyzes in the pH range of 4-6 in contrast to nearly all of the other eukaryotic aspartic proteases, which catalyze best in the pH range of 2-4. A possible structural reason for the higher optimal pH of HIV-1 protease is the absence of a hydrogen bond to the carboxyl group of active-site Asp25, which is nearly universally present in others. To investigate this hypothesis, we have mutated residue 28 in HIV-1 protease from alanine to serine. Both the wild-type and the mutant A28S enzymes have been overexpressed in Escherichia coli using a chemically synthesized gene and purified for a comparative study in enzyme kinetics. The kcat and Km values were determined by a radiometric assay for the wild-type enzyme from pH 3.2 to 7.0, and for the mutant enzyme from pH 3.2 to 6.0. The low pK values of the active site of the free enzyme, pKe1, are 3.3 and 3.4 for the wild-type and mutant enzymes, respectively. The low pK values of the active site of the enzyme bound to substrate, pKes1, are 5.1 and 4.3 for the wild-type and mutant enzymes, respectively. The high pK values of the free enzyme, pKe2, are 6.8 and 5.6, and the corresponding ones for the substrate-bound enzyme, pKes2, are 6.9 and 6.0 for the wild-type and mutant enzymes, respectively. The lowering of pK values in mutant HIV-1 protease indicates that the hydroxyl group of Ser28 forms a new hydrogen bond to active-site Asp25 to increase its acidity. PMID- 1761539 TI - A nucleolar 2'-O-methyltransferase. Specificity and evidence for its role in the methylation of mouse 28 S precursor ribosomal RNA. AB - Methylation of ribose moieties appears to be an essential post-transcriptional event in ribosomal RNA maturation. Although the sites of ribose methylation have been identified, the components involved in the 2'-O-methylation of precursor ribosomal RNA in mammalian cells have not yet been elucidated. To investigate the involvement of a recently isolated nucleolar 2'-O-methyltransferase in this process, an in vitro synthesized 28 S rRNA transcript containing a unique tandem triple 2'-O-methylated ribose site was used as a substrate. Activity assays demonstrated that this transcript served as a substrate for the nucleolar 2'-O methyltransferase. The distribution of incorporated methyl groups was determined by hydrolyzing the 2'-O-methylated transcript with RNase followed by chromatography of the digested products on an anion-exchange high performance liquid chromatography column. Results showed one unique RNase-resistant 2'-O methylated product, a tetramer. The position of the tetrameric sequence in the 28 S rRNA transcript was determined using RNase protection analysis which mapped the methylations to a 20-nucleotide region spanning the unique tandem triple 2'-O methylated ribose site in 28 S rRNA. To confirm the absolute specificity of methylation, direct sequence analysis was carried out on the tandem triple 2'-O methylated tetramer. The sequence determined for the tetramer, AmGmCmA, corresponded exactly with that reported from in vivo studies. These findings demonstrate that the purified nucleolar 2'-O-methyltransferase can accurately methylate at a specific site of an in vitro derived preribosomal RNA transcript and support the proposed involvement of this nucleolar enzyme in ribosomal RNA maturation. PMID- 1761540 TI - Mutation of invariant cysteines of mammalian metallothionein alters metal binding capacity, cadmium resistance, and 113Cd NMR spectrum. AB - Using a yeast expression vector system, we have expressed both wild type and six mutated Chinese hamster metallothionein coding sequences in a metal-sensitive yeast strain in which the endogenous metallothionein gene has been deleted. The mutant proteins have single or double cysteine to tyrosine replacements (C13Y, C50Y, and C13,50Y), single cysteine to serine replacements (C13S and C50S), or a single cysteine to alanine replacement (C50A). These proteins function in their yeast host in cadmium detoxification to differing extents. Metallothioneins which contain a cysteine mutation at position 50 (C50Y, C50S, C50A, and C13,50Y) conferred markedly less cadmium resistance than wild type metallothionein, or metallothionein with a single cysteine mutation at position 13 (C13Y and C13S). Wild type and three of the mutant Chinese hamster metallothioneins (C13Y, C50Y, and C13,50Y) were purified from yeast grown in subtoxic levels of either CdCl2 or 113CdCl2. All three of the mutant proteins bound less cadmium than the wild type protein when metal-binding stoichiometries were determined. The one-dimensional 113Cd NMR spectrum of the recombinant wild type Chinese hamster metallothionein was compared to the spectra of native rat and rabbit liver metallothioneins. The close correspondence between the 113Cd chemical shifts in these metallothioneins is consistent with the presence of two separate metal clusters, A and B, corresponding, respectively, to the alpha- and beta-domains, in the recombinant metallothionein. The one-dimensional 113Cd NMR spectra recorded on each of the three mutant metallothioneins, on the other hand, provide some indication as to the structural basis for the reduced, by one, metal stoichiometry of each of the mutant metallothioneins. For the C13Y mutant, it appears that the beta-domain now binds a total of two metal ions whereas with the C50Y mutant, the alpha-domain appears metal-deficient. For the double mutant, C13,50Y, the 113Cd resonances are indicative of major structural reorganizations in both domains. PMID- 1761541 TI - Differential regulation of antioxidant enzymes in response to oxidants. AB - We have demonstrated the selective induction of manganese superoxide dismutase (MnSOD) or catalase mRNA after exposure of tracheobronchial epithelial cells in vitro to different oxidant stresses. Addition of H2O2 caused a dose-dependent increase in catalase mRNA in both exponentially growing and confluent cells. A 3 fold induction of catalase mRNA was seen at a nontoxic dose of 250 microM H2O2. Increase in the steady-state mRNA levels of glutathione peroxidase (GPX) and MnSOD were less striking. Expression of catalase, MnSOD, and GPX mRNA was highest in confluent cells. In contrast, constitutive expression of copper and zinc SOD (CuZnSOD) mRNA was greatest in dividing cells and was unaffected by H2O2 in both exponentially growing and confluent cells. MnSOD mRNA was selectively induced in confluent epithelial cells exposed to the reactive oxygen species-generating system, xanthine/xanthine oxidase, while steady-state levels of GPX, catalase, and CuZnSOD mRNA remained unchanged. The 3-fold induction of MnSOD mRNA was dose dependent, reaching a peak at 0.2 unit/ml xanthine oxidase. MnSOD mRNA increases were seen as early as 2 h and reached maximal induction at 24 h. Immunoreactive MnSOD protein was produced in a corresponding dose- and time-dependent manner. Induction of MnSOD gene expression was prevented by addition of actinomycin D and cycloheximide. These data indicate that epithelial cells of the respiratory tract respond to different oxidant insults by selective induction of certain antioxidant enzymes. Hence, gene expression of antioxidant enzymes does not appear to be coordinately regulated in these cell types. PMID- 1761542 TI - Alteration of the binding specificity of cellular retinol-binding protein II by site-directed mutagenesis. AB - Rat cellular retinol-binding protein II (CRBP II) is an abundant 134-residue intestinal protein that binds all-trans-retinol and all-trans-retinal. It belongs to a family of homologous, 15-kDa cytoplasmic proteins that bind hydrophobic ligands in a noncovalent fashion. These binding proteins include a number of proteins that bind long chain fatty acids. X-ray analyses of the structure of two family members, rat intestinal fatty acid-binding protein and bovine myelin P2 protein, indicate that they have a high degree of conformational similarity and that the carboxylate group of their bound fatty acid interacts with a delta guanidium group of at least 1 of 2 "buried" arginine residues. These 2 Arg residues are conserved in other family members that bind long chain fatty acids and in cellular retinoic acid-binding protein, but are replaced by Gln109 and Gln129 in CRBP II. We have genetically engineered two amino acid substitutions in CRBP II: 1) Gln109 to Arg and 2) Gln129 to Arg. The purified Escherichia coli derived CRBP II mutant proteins were analyzed by fluorescence and nuclear magnetic resonance spectroscopy. Both mutants exhibit markedly decreased binding of all-trans-retinol and all-trans-retinaldehyde, but no increased binding of all trans-retinoic acid. Arg substitution for Gln109 but not for Gln129 produces a dramatic increase in palmitate binding activity. Analysis of the endogenous fatty acids associated with the purified E. coli-derived proteins revealed that E. coli derived intestinal fatty acid binding protein and the Arg109 CRBP II mutant are complexed with endogenous fatty acids in a qualitatively and quantitatively similar manner. These results provide evidence that this internal Arg may play an important role in the binding of long chain fatty acids by members of this protein family. PMID- 1761543 TI - N-acylation of Aplysia egg-laying hormone with biotin. Characterization of bioactive and inactive derivatives. AB - Chemical modification of the egg-laying hormone (ELH) of Aplysia by reaction with the N-hydroxysuccinimide ester of biotin, which contained 6-aminohexanoic acid as spacer, yielded seven distinct derivatives that were readily separated by reversed-phase high performance liquid chromatography. The derivatives were chemically characterized by amino acid compositional analysis, sequence analysis, and mass spectrometry. The seven derivatives resulted from combinations of differential modification of the three amino groups in the ELH molecule located at Ile1 (alpha-NH2), Lys8, and Lys36. Of the seven derivatives formed, only one, monobiotinyl Lys36-ELH, was biologically active in eliciting egg-laying activity and altering the electrophysiological activity of the abdominal ganglion neuron R15 and LB and LC cluster neurons. In addition, evaluation of the time course of biotinylation of ELH revealed that the relative rate of amino group reactivity was epsilon-NH2-Lys36 greater than epsilon-NH2-Lys8 much greater than alpha-NH2 Ile1. The slow rate of reaction of the terminal alpha-amino group suggested that it was relatively inaccessible to biotinylation, possibly due to conformational factors or to ion-pair formation with an unidentified carboxyl group. Loss of bioactivity of ELH monobiotinylated on the alpha-amino group, coupled with the unusually low reactivity of the alpha-amino group, provided strong evidence for the importance of the alpha-amino group in ELH function. Furthermore, the development and availability of a bioactive ELH probe should greatly facilitate the isolation, characterization, and localization of the ELH receptor. PMID- 1761544 TI - The 5'-flanking region of the human CGL-1/granzyme B gene targets expression of a reporter gene to activated T-lymphocytes in transgenic mice. AB - The human CSP-B/CGL-1 gene is the homologue of the mouse granzyme B/CCPI gene and encodes a cytotoxic T-lymphocyte-specific serine protease. We have used regulatory sequences upstream from the CSP-B gene to drive human growth hormone gene expression in transgenic mice. Eleven founder mice were screened for transgene expression in activated T-cells. Expression was detected in 10 mice; levels of expression were integration site-dependent. The transgene was not expressed in resting lymphocytes but could be activated by treatment with concanavalin A or interleukin-2, indicating that CSP-B regulatory sequences are responsive to signals originating at either the T-cell receptor or the interleukin-2 receptor. Transgene expression was detected at the whole organ level only in lymph nodes and small intestine, where endogenous mouse CCPI mRNA was also present. The time course of transgene activation in T-lymphocytes was similar to that of the mouse CCPI gene. No differences in levels of expression of the transgene were observed in activated lymphocyte populations that had been depleted of either CD4+ or CD8+ cells; in contrast, the mouse CCPI gene was expressed primarily in CD8+ cells. Six CD4+ T-cell clones with Th0, Th1, or Th2 phenotypes were generated from a transgenic animal. All clones expressed moderate to high levels of the transgene, but only three clones expressed mouse CCPI, indicating that the transgene is disregulated in CD4+ T-cell subsets. The CSP-B regulatory unit represents a novel reagent for targeting gene expression to activated T-lymphocytes. PMID- 1761545 TI - Increase in eukaryotic initiation factor 2B activity following fertilization reflects changes in redox potential. AB - One of the factors involved in the postfertilization activation of protein synthesis in the sea urchin, Strongylocentrotus purpuratus, is the activation of eIF-2B, the initiation factor responsible for guanine nucleotide exchange on eIF 2. Cell-free translation systems from unfertilized eggs are stimulated by added eIF-2B, although this dependency is rapidly lost in translation systems prepared at various times following fertilization. Cell-free translation systems prepared from unfertilized eggs show significantly lower eIF-2B activities than those prepared from 2-h embryos. However, the provision of an NADPH regeneration system significantly stimulates eIF-2B activity in egg extracts and, in addition, stimulates both binding of initiator tRNA to the small ribosomal subunit and protein synthetic activity. These data suggest that the activation of eIF-2B following fertilization reflects the fertilization-induced increase in NADPH levels. PMID- 1761546 TI - Regulation of the human ApoA-II gene by the synergistic action of factors binding to the proximal and distal regulatory elements. AB - We have recently shown that the human apoA-II promoter contains a set of 11 distal regulatory elements between nucleotides -903 and -255 and three proximal regulatory elements between nucleotides -126 and -33 that are essential for hepatic and intestinal transcription of the apoA-II gene (Chambaz, J., Cardot, P., Pastier, D., Zannis, V. I., and Cladaras, C. (1991) J. Biol. Chem. 266, 11676 11685). Deletion or nucleotide substitution analysis has shown that alterations in elements L (nucleotides -803 to -773) and K (nucleotides -760 to -743) reduced hepatic transcription to 25 and 20% and intestinal transcription to 8 and 4% of control, respectively, as measured by chloramphenicol acetyltransferase assays, indicating that these elements play an important regulatory role. Nucleotide substitutions in element AB (nucleotides -65 to -33) reduced hepatic and intestinal transcription to 60 and 36% of control, respectively. The factors that recognize regulatory regions L, K, and AB were analyzed by DNA binding gel electrophoretic and competition assays. This analysis has shown that elements AB, K, and L bind with different affinities to a newly characterized heat-stable factor, CIIIB1, which is a transcriptional activator of the human apoC-III gene (Ogami, K., Kardassis, D., Cladaras, C., and Zannis, V. I. (1991) J. Biol. Chem. 266, 9640-9646). In addition, elements AB and K bind a heat-labile activity, designated AIIAB1, and element L binds to several CCAAT box binding activities. Mutations in domain L that prevented the binding of CCAAT box binding activities reduced both hepatic and intestinal transcription to 30% of control, indicating the importance of these factors in transcription. Simultaneous nucleotide substitutions that prevented the binding of CIIIB1 activity in elements AB, K, and L reduced hepatic and intestinal transcription to 7 and 6% of control, respectively, suggesting that the synergistic interaction of CIIIB1 (bound to the proximal and distal regulatory elements) with CCAAT box proteins (bound to element L) can modulate the level of transcription of the human apoA-II gene. PMID- 1761547 TI - Variants of a Leishmania surface antigen derived from a multigenic family. AB - The promastigote surface antigen-2 (PSA-2) complex comprises a group of immunogenic surface antigens linked to the surface of the Leishmania major promastigote with glycosylphosphatidylinositol anchors. The L. major genome contains at least 14 PSA-2 genes on a 950-kilobase chromosome and comprising approximately 20% of the length of this chromosome. The sequence of three independent, but incomplete, PSA-2 cDNAs and one genomic fragment encoding a complete PSA-2 coding sequence were compared. PSA-2 genes encode polypeptides exhibiting 22-25aa tandem repeat elements, threonine-rich segments which vary between genes, a conserved COOH-terminal cysteine-rich region, and a conserved GPI anchor signal sequence. PSA-2 genes appear to be transcribed in a complex manner with multiple RNAs. The complex genomic organization of PSA-2 genes is present in other members of the genus suggesting that PSA-2 function is important for the biology of Leishmania. PMID- 1761548 TI - Characterization of cross-linking of cell walls of Bacillus subtilis by a combination of magic-angle spinning NMR and gas chromatography-mass spectrometry of both intact and hydrolyzed 13C- and 15N-labeled cell-wall peptidoglycan. AB - Cross-polarization magic-angle spinning 13C and 15N NMR, rotational-echo double resonance 13C NMR, and delays alternating with nutation for tailored excitation difference 13C NMR spectra have been obtained from lyophilized cell walls of Bacillus subtilis grown on a synthetic medium containing D,L-[2-13C, 15N]aspartate and D-[1-13C]alanine. Label from aspartate is incorporated into D glutamic acid and m-diaminopimelic acid of cell-wall peptidoglycan, while label from alanine appears in the C-1 positions of both D- and L-alanyl residues. The cross-link index (the fraction of peptide stems joined by an isopeptide covalent bond) is obtained directly from analysis of the results of the 13C NMR experiments. However, specific isotopic enrichments of cell-wall components cannot be obtained from NMR data alone. The latter are determined either from a gas chromatographic-mass spectrometric analysis of the amino acids derived from hydrolysis of cell-wall peptidoglycan, or from a combination of NMR and gas chromatographic-mass spectrometric results. The combined analysis is overdetermined and so involves the least error for evaluations of both the cross link index and the isotopic enrichments. The cross-link index is 0.33 +/- 0.03 for cell walls of B. subtilis grown in the presence of the antibiotic, cephalothin. PMID- 1761549 TI - Double-mixing kinetic studies of the reactions of monoliganded species of hemoglobin: alpha 2(CO)1 beta 2 and alpha 2 beta 2(CO)1. AB - The kinetics of CO association to and dissociation from the two isomers of monoliganded species alpha ICO beta I(alpha II beta II) and alpha I beta I (alpha II beta COII) has been studied by double-mixing stopped-flow and microperoxidase methods. The monoliganded species were generated by hybridization between excess ferric Hb and alpha CO2 beta +2 or alpha +2 beta CO2 prepared by high-pressure liquid chromatography (HPLC). The results indicated that: 1) there were no significant differences in the reactivities of alpha and beta chains in the first step of ligation; 2) in the second step of ligation there was significant cooperativity in the reaction of deoxyhemoglobin with 0.05 or 0.1 equivalent of CO. Diliganded species were therefore formed in significant amounts. The double mixing HPLC results suggested that in the second step of ligation alpha chains reacted faster than the beta chains, and the main diliganded species formed was alpha I beta ICO (alpha IICO beta II) or its isomer alpha ICO I(alpha II beta IICO). These results seem to indicate that the reaction of the first CO is mostly random and in the second step of ligation CO binds more to the tetramers in which one beta chain is already ligated: alpha I beta I (alpha II beta II) + CO--- alpha ICO beta I (alpha II beta II) and alpha I beta ICO (alpha II beta II) + CO- --alpha I beta ICO (alpha IICO beta II). PMID- 1761550 TI - How does trp repressor bind to its operator? AB - Three explanations have been advanced to account for the unexpected absence of direct hydrogen bonds and presence of a buried water layer in the co-crystal-line complex of Escherichia coli trp repressor with DNA. We present results of physical and biochemical measurements that address the testable predictions of each model. We find that the DNA oligomer used for co-crystallization binds to the repressor with high affinity and specificity, and 1:1 stoichiometry, consistent with other evidence that this sequence represents the true operator target for a single repressor dimer. A proposed alternative DNA sequence binds weaker and with higher stoichiometry, consistent with a cooperative binding mode. The operator DNA in solution has a B-form helical structure in the presence and absence of repressor. Affinity of repressor for operator is altered under the conditions used for cocrystal growth. PMID- 1761551 TI - Identification of a sequence of human activated protein C (residues 390-404) essential for its anticoagulant activity. AB - Activated protein C (APC) exerts its physiologic anticoagulant role by proteolytic inactivation of the blood coagulation cofactors Va and VIIIa. To identify the regions on the surface that mediate anticoagulant activity, 26 synthetic peptides were prepared representing 90% of the human protein C heavy chain primary structure and tested for their ability to inhibit APC anticoagulant activity. Peptide-(390-404) specifically inhibited APC activity in activated partial thromboplastin time and Xa-1-stage coagulation assays in normal, in protein S-depleted and Factor VIII-deficient plasma with 50% inhibition at 5 microM peptide. Polyclonal antibodies raised against this peptide and immunoaffinity-purified on a protein C-Sepharose column inhibited APC anticoagulant activity in activated partial thromboplastin time and Xa-1-stage assays in normal, protein S-depleted, and Factor VIII-deficient plasma with half maximal inhibition at 30 nM anti-(390-404) antibody. Neither the peptide-(390 404) nor the anti-(390-404) antibodies inhibited APC amidolytic activity or the reaction of APC with recombinant [Arg358] alpha 1-antitrypsin. Furthermore, in a purified system, peptide-(390-404) inhibited APC-catalyzed inactivation of Factor Va in the presence as well as in the absence of phospholipids with 50% inhibition at 4 microM peptide. These data suggest that the region containing residues 390 404 in APC is essential for anticoagulant activity and is available to interact with antibodies or with other proteins such as the macromolecular substrates Factors Va or VIIIa. PMID- 1761552 TI - Insect immunity. Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family. AB - Injection of heat-killed bacteria into larvae of the large tenebrionid beetle Zophobas atratus (Insecta, Endopterygota, Coleoptera) results in the appearance in the hemolymph of a potent antibacterial activity as evidenced by a plate growth inhibition assay. We have isolated three peptides (A-C) from this immune hemolymph which probably account for most of this activity. Their primary structures were established by a combination of peptide sequencing and molecular mass determination by mass spectrometry. Peptide A, which is bactericidal against Gram-negative cells, is a 74-residue glycine-rich molecule with no sequence homology to known peptides. We propose the name coleoptericin for this novel inducible antibacterial peptide. Peptides B and C are isoforms of a 43-residue peptide which contains 6 cysteines and shows significant sequence homology to insect defensins, initially reported from dipteran insects. This peptide is active against Gram-positive bacteria. The results are discussed in connection with recent studies on inducible antibacterial peptides present in the three other major orders of the endopterygote clade of insects: the Lepidoptera, Diptera, and Hymenoptera. PMID- 1761553 TI - Purification and characterization of aginactin, a newly identified agonist regulated actin-capping protein from Dictyostelium amoebae. AB - Amoeboid chemotaxis involves a regulated increase in actin nucleation activity that is correlated with an increase in actin polymerization occurring seconds after chemotactic stimulation (Carson, M., Weber, A., and Zigmond, S. H. (1986) J. Cell Biol. 103, 2707-2714; Hall, A. L., Warren, V., Dharmawardhane, S., and Condeelis, J. (1989) J. Cell Biol. 109, 2207-2213). We report the isolation and characterization of an agonist-regulated capping protein, aginactin, from Dictyostelium that may regulate these changes in actin nucleation activity. Aginactin is isolated from low speed supernatants of starved amoebae by sequential anion exchange, hydrophobic interaction, fast protein liquid chromatography anion exchange, and hydroxyapatite chromatography. Aginactin migrates with an apparent molecular weight of 70,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis gels and gel filtration columns, suggesting that it is a globular monomer. Aginactin is a barbed-end capping protein by several criteria. It inhibits the rate and final extent of actin polymerization and increases the apparent critical concentration at substoichiometric ratios to actin. It also inhibits depolymerization of F-actin and inhibits polymerization at the barbed end of Limulus acrosomal bundles. Aginactin is unaffected by micromolar Ca2+, and it neither severs F-actin nor nucleates actin polymerization in either the presence or absence of Ca2+. Aginactin binds to and cosediments with F-actin and has an apparent Kd for capping F-actin of 2.7 nM. PMID- 1761554 TI - The Saccharomyces cerevisiae TRG1 gene is essential for growth and encodes a lumenal endoplasmic reticulum glycoprotein involved in the maturation of vacuolar carboxypeptidase. AB - We have isolated and mapped to the left end of chromosome III a single-copy gene (TRG1) encoding a 72-kDa glycoprotein, by screening a yeast genomic library with a DNA probe specifying the catalytic center (APWCGHCK) of thioredoxin-related proteins. the TRG1 gene sequence predicts an amino-terminal leader peptide, two thioredoxin-like domains, five N-glycosylation sites and a carboxyl-terminal HDEL retention signal. The TRG1 protein shows about equal sequence similarity to a mammalian multifunctional protein family residing in the lumen of the endoplasmic reticulum (ER), and to a putative cytosolic alpha form of phosphoinositide specific phospholipase C. Haploid cells do not survive TRG1 gene disruptions, unless an additional wild-type copy is generated by interchromosomal transposition. Antibodies raised against synthetic amino- and carboxyl-terminal epitopes recognize a pair of lumenl ER glycoproteins (gp70/72) and a cytosolic 48 kDa protein. A 1.8-kilobase TRG1 transcript was translated by a reticulocyte lysate into a 60-kDa protein, which was translocated and processed to a 72-kDa glycoprotein in the presence of ER membrane vesicles. The TRG1 gene was placed under the control of the galactose-inducible and glucose-repressible GAL1 promoter, leading to growth arrest in glucose media. Glucose repression of the TRG1 gene caused the disappearance of gp72 and the accumulation of procarboxypeptidase. Our data indicate that the TRG1 gene encodes a growth essential lumenal ER glycoprotein involved the maturation of vacuolar carboxypeptidase. PMID- 1761555 TI - Increase of Cu,Zn-superoxide dismutase activity during differentiation of human K562 cells involves activation by copper of a constantly expressed copper deficient protein. AB - Cu,Zn-superoxide dismutase activity, expressed on the basis of cell number, increased by 50% during sodium butyrate-induced differentiation of human K562 erythroleukemia cells. The increased enzyme activity was found to be concomitant with constant Cu,Zn-superoxide dismutase mRNA and immunoreactive protein levels and was accompanied by a rise in intracellular copper and glutathione. Incubation of K562 cell homogenates with copper caused an increase of Cu,Zn-superoxide dismutase activity which reached the levels observed after differentiation in the presence of sodium butyrate. The same treatment led to no significant activity increase in homogenates derived from differentiated cells. Externally added ceruloplasmin increased both intracellular copper levels and Cu,Zn-superoxide dismutase activity in undifferentiated cells to a level comparable with that observed after induction of differentiation. Both increments were abolished by depletion of cell glutathione. Cu,Zn-superoxide dismutase purified from control cells had both a lower kcat and a lower copper content than the enzyme purified from differentiated cells. From these data we conclude that: 1) Cu,Zn-superoxide dismutase is present in K562 cells also under the form of a less active copper deficient enzyme, 2) the extent of enzyme activation is regulated post translationally by differential delivery of copper as a function of differentiation stage, and 3) glutathione is likely to play a role in delivering copper to the copper-deficient protein in intact K562 cells. PMID- 1761556 TI - Transcription complex formation at the mouse rDNA promoter involves the stepwise association of four transcription factors and RNA polymerase I. AB - We have used purified transcription factors and RNA polymerase I (pol I) to analyze the individual steps involved in the formation of transcription initiation complexes at the mouse ribosomal gene promoter in vitro. Complete assembly of transcription complexes requires pol I and at least four auxiliary factors, termed TIF-IA, TIF-IB, TIF-IC, and UBF. Preincubation and template commitment, as well as order of addition protocols, were used to discriminate between various intermediate complexes generated during assembly of the initiation complex. As a first step, TIF-IB binds to the core promoter, a process that is facilitated by the upstream control element and the upstream binding factor (UBF). Binding of TIF-IB to the rDNA promoter results in the formation of a functional preinitiation complex (complex 1), which is stable for many rounds of transcription. UBF, which on its own does not stably associate with the rDNA promoter, triggers a 5-10-fold increase in the overall amount of this primary complex. Following binding of TIF-IB and UBF to the template DNA, pol I and TIF IC successively bind, yielding complexes 2 and 3, respectively. Transcription competent initiation complexes are built up by the final association of the growth-regulated factor TIF-IA. The various complexes can be distinguished by their different sensitivity to Sarkosyl. Only the complete complex consisting of all four factors and pol I shows resistance to intermediate concentrations of Sarkosyl (0.045%) and is competent to catalyze the formation of the first phosphodiester bond. The initiated complex is, on the other hand, resistant to high concentrations of Sarkosyl (0.3%). The hierarchical nature of the different complexes formed suggests a model for transcription initiation and predicts functions for the individual factors. PMID- 1761557 TI - Protein components of the nonactivated glucocorticoid receptor. AB - The nonactivated glucocorticoid receptor (Mr approximately 350,000) of WEHI-7 mouse lymphoma cells was investigated with respect to the stoichiometry of protein subunits. Cross-linking patterns obtained by affinity labeling and denaturing gel electrophoresis revealed a heterotetramer consisting of one receptor polypeptide in association with two 90- and one approximately 50-kDa subunits. The receptor stabilized by molybdate, disulfide bond formation, or chemical cross-linking was purified roughly 6000-fold by immunoaffinity chromatography and analyzed by gel electrophoresis and immunoblotting. The 90-kDa component was consistently detected in a 2:1 ratio with respect to the receptor polypeptide and was identified as the 90-kDa heat shock protein, hsp90. A 70-kDa heat shock protein was found in both stabilized and nonstabilized receptors and bound to the immunomatrix independent of receptor. The additional receptor subunit was unequivocally identified as the 59-kDa protein previously described (Tai, P.-K. K., Maeda, Y., Nakao, K., Wakim, N. G., Duhring, J. L., and Faber, L. E. (1986) Biochemistry 25, 5269-5275). This component was found only in complexes cross-linked via amino groups. It was removed from the molybdate-stabilized receptor under our purification conditions, thus leaving behind a trimer composed of the receptor polypeptide and two molecules of hsp90. In the absence of hormone, the receptor had the same subunit composition as in its presence. PMID- 1761558 TI - Structural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution. AB - The structure of rat carboxypeptidase A2 (CPA2), which has a unique specificity for tryptophan-containing COOH-terminal peptides, has been determined in an unliganded state at 1.9-A resolution and refined to a crystallographic R-factor of 18.3%. Comparison of the structure of CPA2 with that of bovine carboxypeptidase A (referred to here as CPA1) reveals that the specificity of the former for larger amino acids probably arises from two amino acid replacements within the binding cavity (Thr268----Ala and Leu203----Met), coupled with differences in the positions of conserved residues in a surface loop on one face of the specificity pocket. The position of the reactive-site surface loop may be affected also by a disulfide bridge between Cys210 and Cys244. In this unliganded form of the enzyme, Tyr248 takes up a position interior to the specificity pocket and is distinct from that observed in bovine CPA1. The structural differences between CPA1 and CPA2 correlate strongly with crystallographically determined temperature factors and thus appear to be largest where the enzyme is flexible. PMID- 1761559 TI - A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene. AB - The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-terminal peptide, calcitonin, and a carboxyl-terminal peptide (CCP I). Calcitonin gene-related peptide (CGRP) mRNA is produced in neuronal cells by splicing of the three common exons to the fifth exon and the polyadenylated sixth exon, leading to the production of a CGRP precursor. Our studies concerning the expression of the calcitonin/CGRP gene in human medullary thyroid carcinoma revealed the presence of a new RNA transcript. Amplification by polymerase chain reaction and direct sequencing showed that the novel transcript is composed of exons 1, 2, and 3, part of exon 4, exon 5, and a polyadenylated exon 6. This transcript contains an open reading frame coding for the known amino-terminal and calcitonin peptides, as well as for a novel calcitonin carboxyl-terminal peptide, CCP II. This third alternative pathway utilizes an internal donor site within the exon coding for calcitonin. The presence of CCP II was demonstrated in plasma and thyroidal tissues of medullary thyroid carcinoma patients, implying that this novel mRNA is actively translated in medullary thyroid carcinoma. PMID- 1761560 TI - The role of N-glycosylation of GLUT1 for glucose transport activity. AB - To elucidate a functional role of N-glycosylation in glucose transporters, we introduced oligonucleotide-directed mutagenesis in GLUT1 cDNA to remove the possible site for N-linked glycosylation. The wild-type and the mutated GLUT1 cDNAs which induced a mutation of Asn at residue 45 to Asp, Tyr, or Gln were transfected and stably expressed into Chinese hamster ovary cells. The expressed wild-type and the mutated GLUT1 was demonstrated to be a broad band of a 45-60 kDa form and a sharp band of a 38-kDa form on Western blot analysis, respectively, indicating no glycosylation in the mutated GLUT1. Although the cell surface labeling of the glucose transporters demonstrated the presence of the glycosylation-defective glucose transporters on the cells surface, photoaffinity labeling of glycosylation-defective GLUT1 with [3H] cytochalasin B and a photoreactive mannose derivative, [3H]2-N-4-(1-azi-2,2,2,trifluoroethyl)benzoyl 1,3-bis(D-mannos+ ++-4-yloxy)-2- propylamine in the membranes was observed to be 40-70 and 15-30% of that of the wild-type GLUT1, respectively. The kinetic study of 2-deoxyglucose uptake revealed that the glycosylation-defective GLUT1 had a 2 2.5-fold greater Km value for 2-deoxyglucose uptake compared with the wild-type GLUT1. These observations strongly suggest that 1) N-glycosylation of GLUT1 glucose transporter is only on Asn 45 and 2) N-glycosylation plays an important role in maintaining a structure of glucose transporter with high affinity for glucose, thus, with high transport activity. PMID- 1761561 TI - The functional size of ferrochelatase determined in situ by radiation inactivation. AB - Ferrochelatase (EC 4.99.1.1) catalyzes the final step of heme biosynthesis, the insertion of iron(II) into protoporphyrin. It is an integral protein of the inner mitochondrial membrane. The functional size of bovine hepatic ferrochelatase has been studied in situ using radiation inactivation analysis. The functional unit required for enzymic activity in intact mitochondria was found to have a mass of 82 +/- 13 kDa. In contrast, the structural unit (evaluated in immunoblots following sodium dodecyl sulfate-polyacrylamide gel electrophoresis) has a mass of 40 +/- 10 kDa. Similar results were obtained when irradiation was performed on sodium cholate-solubilized mitochondria. The presence or absence of dithiothreitol during irradiation had no effect on target sizes obtained from either intact or solubilized mitochondria. Pairwise comparison of the functional and structural target sizes from each set of irradiated samples yielded a ratio of 2.0 +/- 0.4. Previous studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration chromatography have shown that a Mr 40,000 peptide is associated with ferrochelatase activity. This study shows that the functional size of bovine ferrochelatase is approximately 80 kDa; the data are most consistent with a model for active ferrochelatase composed of two structural subunits of about 40 kDa each. PMID- 1761562 TI - Cryoelectron microscopy of mammalian pyruvate dehydrogenase complex. AB - Cryoelectron microscopy has been performed on frozen-hydrated pyruvate dehydrogenase complexes from bovine heart and kidney and on various subcomplexes consisting of the dihydrolipoyl transacetylase-based (E2) core and substoichiometric levels of the other two major components, pyruvate dehydrogenase (E1) and dihydrolipoyl dehydrogenase (E3). The diameter of frozen hydrated pyruvate dehydrogenase complex (PDC) is 50 nm, which is significantly larger than previously reported values. On the basis of micrographs of the subcomplexes, it is concluded that the E1 and E3 are attached to the E2-core complex by extended (4-6 nm maximally) flexible tethers. PDC constructed in this manner would probably collapse and appear smaller than its native size when dehydrated, as was the case in previous electron microscopy studies. The tether linking E1 to the core involves the hinge sequence located between the E1-binding and catalytic domains in the primary sequence of E2, whereas the tether linking E3 is probably derived from a similar hinge-type sequence in component X. Tilting of the E2-based cores and comparison with model structures confirmed that their overall shape is that of a pentagonal dodecahedron. The approximately 6 copies of protein X present in PDC do not appear to be clustered in one or two regions of the complex and are not likely to be symmetrically distributed. PMID- 1761563 TI - Identification and purification of a peroxisomal branched chain fatty acyl-CoA oxidase. AB - Isoprenoid (branched) fatty acids such as pristanic acid can be degraded via beta oxidation in peroxisomes. We synthesized 2-methylpalmitoyl-CoA as a model substrate in order to study the first step of the peroxisomal beta-oxidation of branched fatty acids, catalyzed by an acyl-CoA oxidase. 2-Methylpalmitoyl-CoA oxidase activity was found in rat liver homogenates. Subcellular fractionation demonstrated that the oxidase was confined to peroxisomes. 2-Methylpalmitoyl-CoA oxidase was also present in kidney and intestine. It was not induced in liver or in the extrahepatic tissues by treatment of rats with peroxisome proliferators or by feeding diets containing excess isoprenoids. The enzyme was partially purified together with palmitoyl-CoA oxidase and trihydroxycoprostanoyl-CoA oxidase by heat treatment and ammonium sulfate fractionation of liver extracts. The partially purified preparation was chromatographed on various columns. 2 Methylpalmitoyl-CoA oxidase could be separated from the inducible (by peroxisome proliferators) palmitoyl-CoA oxidase and from trihydroxycoprostanoyl-CoA oxidase, but it always coeluted with the noninducible palmitoyl-CoA oxidase, recently described by us (Schepers, L., Van Veldhoven, P. P., Casteels, M., Eyssen, H. J., and Mannaerts, G. P. (1990) J. Biol. Chem. 265, 5242-5246). 2-Methylpalmitoyl-CoA oxidase was purified to near homogeneity in three chromatographic steps (anion exchange, hydroxylapatite, and gel filtration). Its apparent molecular mass is approximately 415 kDa, and it consists of identical subunits of approximately 70 kDa. The enzyme oxidized 2-methylpalmitoyl-CoA twice as rapidly as palmitoyl-CoA and pristanoyl-CoA as rapidly as palmitoyl-CoA, so that it can be considered as a branched fatty acyl-CoA oxidase. Since pristanoyl-CoA is one of its naturally occurring substrates we propose to name this enzyme pristanoyl-CoA oxidase. PMID- 1761564 TI - Persistent intracellular calcium pool depletion by thapsigargin and its influence on cell growth. AB - The intracellular Ca2+ pump inhibitor, thapsigargin, added to DDT1MF-2 smooth muscle cells in culture, irreversibly inhibited accumulation of Ca2+ within cells, permanently emptied the inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool, and simultaneously induced profound alteration of cell growth. After only a brief (30-min) treatment of cultured cells with 3 microM thapsigargin followed by extensive washing, the total releasable InsP3-sensitive Ca2+ pool remained entirely empty, even after 7 days of culture without thapsigargin. After thapsigargin treatment, cells retained viability, usual morphology, and normal mitochondrial function. Despite the otherwise normal appearance and function of thapsigargin-treated cells, cell division was completely blocked by thapsigargin. DNA synthesis was completely inhibited when thapsigargin was added immediately after passaging, but was suppressed only slowly (4-6 h) when added to rapidly synthesizing cells (24 h after passaging). Protein synthesis was reduced by approximately 70% in thapsigargin-treated cells. The sensitivity of thapsigargin mediated inhibition of cell division, DNA synthesis, protein synthesis, and Ca(2+)-pumping activity were all similar with the EC50 values for thapsigargin in each case being close to 10 nM. Upon application to DDT1MF-2 cells, thapsigargin transiently increased resting cytosolic Ca2+ (0.15 microM) to a peak of 0.3 microM within 50 s; thereafter, free Ca2+ declined to 0.2 microM by 150 s and continued to slowly decline toward resting levels. Cells treated with thapsigargin for 1-72 h in culture displayed normal resting cytosolic Ca2+ levels. However, application of thapsigargin or epinephrine to such cells resulted in no change in the intracellular Ca2+, indicating that the internal Ca2+ pool remained completely empty. These results suggest that emptying of Ca2+ from intracellular thapsigargin-sensitive Ca(2+)-pumping pools induces profound alteration of cell proliferation. PMID- 1761565 TI - Autoxidation of hemoglobin enhanced by dissociation into dimers. AB - Autoxidation as a function of hemoglobin concentration indicates a 17-fold increase in the rate of autoxidation from 0.25 (%/h) to 4.3 (%/h) when tetrameric oxyhemoglobin dissociates into dimers. As a result of this large enhancement, a contribution of dissociation to the autoxidation is evident even at relatively high concentrations of hemoglobin for which it is usually considered that dissociation can be neglected. The mechanism for this phenomenon is attributed to alterations in the ligand pocket which occur when constraints due to subunit contacts within the R-state are eliminated. PMID- 1761566 TI - Direct analysis of aminoacylation levels of tRNAs in vivo. Application to studying recognition of Escherichia coli initiator tRNA mutants by glutaminyl tRNA synthetase. AB - We describe the use of a gel electrophoretic method for measuring the levels of aminoacylation in vivo of mutant Escherichia coli initiator tRNAs, which are substrates for E. coli glutaminyl-tRNA synthetase (GlnRS) due to an anticodon sequence change. Using this method, we have compared the effects of introducing further mutations in the acceptor stem, at base pairs 1:72, 2:71, and 3:70 and discriminator base 73, on the recognition of these tRNAs by E. coli GlnRS in vitro and in vivo. The effects of the acceptor stem mutations on the kinetic parameters for aminoacylation of the mutant tRNAs in vitro are consistent with interactions seen between this region of tRNA and GlnRS in the crystal structure of tRNA(Gln). GlnRS complex. Except for one mutant, the observed levels of aminoacylation of the mutant tRNAs in vivo agree with those expected on the basis of the kinetic parameters obtained in vitro. We have also measured the relative amounts of aminoacyl-tRNAs for the various mutants and their activities in suppression of an amber codon in vivo. We find that there is, in general, a good correlation between the relative amounts of aminoacyl-tRNAs and their activities in suppression. PMID- 1761567 TI - Functional analysis of the putative catalytic bases His-321 and Ser-368 of Rhodospirillum rubrum ribulose bisphosphate carboxylase/oxygenase by site directed mutagenesis. AB - Numerous candidates have been suggested according to chemical and structural criteria for the active site base of ribulose bisphosphate carboxylase/oxygenase that catalyzes substrate enolization. We evaluate the functional significance of two such candidates, His-321 and Ser-368 of the Rhodospirillum rubrum enzyme, by site-directed mutagenesis. Position 321 mutants retain 3-12% of wild-type rates of both overall carboxylation and the initial enolization, with little effect on Km for CO2 or ribulose bisphosphate. Position 368 mutants exhibit approximately 1% of wild-type carboxylation but 4-9% of enolization, also accompanied by little effect on Km values. The modest catalytic facilitations elicited by these residues are incompatible with either acting as the crucial base. The enhanced efficiency of the position 368 mutants in enolization versus carboxylation clearly indicates that Ser-368 effects catalysis preferentially beyond the point of proton abstraction. Both sets of mutants bind the reaction intermediate analogue, 2-carboxy-D-arabinitol bisphosphate, stoichiometrically. Ligand exchange from complexes with position 321 mutants is increased relative to wild type, whereas complexes with position 368 mutants are more exchange-inert. Therefore, His-321 may assist stabilization of the transition state mimicked by the analogue. PMID- 1761568 TI - Interleukin-5, interleukin-3, and granulocyte-macrophage colony-stimulating factor cross-compete for binding to cell surface receptors on human eosinophils. AB - Human interleukin (IL)-5 receptors were characterized by means of binding studies using bioactive 125I-labeled IL-5. Of purified primary myeloid cells, eosinophils and basophils but not neutrophils or monocytes expressed surface receptors for IL 5. Binding studies showed that eosinophils expressed a single class of high affinity receptors (Ka = 1.2 x 10(10) M-1) with the number of receptors being small (less than 1000 receptors/cell) and varying between individuals. Among several cell lines examined only HL-60 cells showed detectable IL-5 receptors which were small in numbers (200 receptors/cell) and also bound 125I-IL-5 with high affinity. The binding of IL-5 was rapid at 37 degrees C while requiring several hours to reach equilibrium at 4 degrees C. Specificity studies revealed that the two other human eosinophilopoietic cytokines IL-3 and granulocyte macrophage colony-stimulating factor (GM-CSF) inhibited the binding of 125I-IL-5 to eosinophils. No competition was observed by other eosinophil activating or nonactivating cytokines. The inhibition of 125I-IL-5 binding by IL-3 and GM-CSF was partial up to a concentration of competitor of 10(-7) M with GM-CSF consistently being the stronger competitor. Converse experiments using IL-5 as a competitor revealed that this cytokine inhibited the binding of 125I-IL-3 and of 125I-GM-CSF in some but not all the individuals tested, perhaps reflecting eosinophil heterogeneity in vivo. Cross-linking experiments on HL-60 cells demonstrated two IL-5-containing complexes of Mr 150,000 and Mr 80,000 both of which were inhibited by GM-CSF. The competition between IL-5, IL-3, and GM-CSF on the surface of mature eosinophils may represent a unifying mechanism that may help explain the common biological effects of these three eosinophilopoietic cytokines on eosinophil function. This unique pattern of competition may also be beneficial to the host by preventing excessive eosinophil stimulation. PMID- 1761569 TI - Interaction of the UvrABC endonuclease with DNA containing a psoralen monoadduct or cross-link. Differential effects of superhelical density and comparison of preincision complexes. AB - The effect of negative supercoiling on UvrABC incision of covalently closed duplex DNA circles containing either a furan-side monoadduct or a cross-link of 4'-hydroxymethyl-4,5',8-trimethylpsoralen at a unique site was examined. The rate of UvrABC incision of these DNA substrates was measured as a function of superhelical density, sigma, for values of sigma between 0 and -0.050. The monoadducted DNA substrate was incised at close to the maximum rate at all superhelical densities, with only a slight stimulation of activity between sigma = 0 and -0.035. In contrast, efficient UvrABC incision of the cross-linked DNA substrate required the DNA to be underwound, and activity showed a linear dependence on superhelical density up to sigma = -0.035. DNase I protection studies show that in the presence of both UvrA and UvrB a protein complex binds to the site of a psoralen monoadduct or cross-link in linear DNA. This UvrA-UvrB dependent complex binds with similar affinity to both the monoadducted and the cross-linked DNA helices. However, differences in the DNase I footprint on these two DNA substrates indicate that the interaction of this protein complex is different at these two lesions. The addition of UvrC to linear DNA molecules that are saturated at the site of the lesion with the UvrA-UvrB-dependent complex resulted in efficient nicking of the monoadducted DNA, but not the cross-linked DNA. Thus, the properties of a DNA lesion site that lead to UvrAB recognition and binding are not necessarily sufficient to allow incision when all three Uvr subunits are present. We propose that after recognition and binding of a lesion site by the UvrAB complex and prior to incision, the damaged DNA helix undergoes a conformational change such as unwinding or melting that is induced by the lesion-bound Uvr complex. PMID- 1761570 TI - Occurrence of multiple aberrantly spliced mRNAs upon a donor splice site mutation that causes familial lipoprotein lipase deficiency. AB - A donor splice site mutation was found in the lipoprotein lipase (LPL) gene of a patient with familial LPL deficiency. The mutation, a G----A substitution, occurred at the first nucleotide of intron 2. Northern blot analysis of total RNA from the patient showed strikingly low levels of LPL-specific mRNAs. Using the polymerase chain reaction, the LPL mRNA splicing was analyzed in detail. The results demonstrated that no normal splicing occurred at the authentic splice site; rather a cryptic splice site 18 bases upstream from the mutation site was preferentially utilized. Although the resulting alteration in mRNA was a minute in-frame 18-base deletion, the amount of the abnormal transcript was only 1/12 that of the normal. In addition to this major cryptic splice site, we also identified multiple minor sites which were utilized at extremely lower efficiencies. Unexpectedly, one of these minor sites was also used as an alternative splice site in the normal subject at a comparably low efficiency. The sequences of these minor cryptic sites possessed many of the characteristics common to those of other normal splice sites, indicating that even such minor sites should have also been selected according to the general rules for splice site selection. These results demonstrate that upon mutation, a broad spectrum of cryptic splice sites is activated in vivo at the sites' respective efficiencies. PMID- 1761571 TI - Peroxisomal degradation of leukotrienes by beta-oxidation from the omega-end. AB - Chain shortening via beta-oxidation from the omega-end has been recognized as the major pathway for the degradation of cysteinyl leukotrienes as well as leukotriene B4 (LTB4). The metabolic compartmentation of this pathway was studied using peroxisomes purified from normal and clofibrate-treated rat liver. beta Oxidation products of omega-carboxy-LTB4, including omega-carboxy-dinor-LTB4 identified by gas chromatography-mass spectrometry, were formed by the isolated peroxisomes. The reaction was dependent on CoA, ATP, and NAD and was stimulated by FAD. NADPH was necessary for the further metabolism of omega-carboxy-dinor LTB4. Together with microsomes a degradation of omega-carboxy-LTB4 also proceeded in isolated mitochondria in the presence of CoA, ATP, and carnitine. beta Oxidation of the cysteinyl leukotriene omega-carboxy-N-acetyl-leukotriene E4 was observed only with isolated peroxisomes in combination with lipid-depleted microsomes. Direct photoaffinity labeling using omega-carboxy-[3H] LTB4 and omega carboxy-N-[3H]acetyl-LTE4 served to identify peroxisomal leukotriene-binding proteins. The bifunctional protein (EC 4.2.1.17 and 1.1.1.35) and 3-ketoacyl-CoA thiolase (EC 2.3.1.16) of the peroxisomal beta-oxidation system were the predominantly labeled polypeptides as revealed by precipitation with monospecific antibodies. In vivo studies with N-acetyl-[3H2]LTE4, N-acetyl-[3H8]LTE4, and N [14C]acetyl-LTE4 after treatment with the peroxisome proliferator clofibrate indicated formation and biliary excretion of large amounts of metabolites more polar than omega-carboxy-tetranor-N-acetyl-LTE3 including omega-carboxy-tetranor delta 13-N-acetyl-LTE4 and omega-carboxy-hexanor-N-acetyl-LTE3. Increased formation of beta-oxidized catabolites of N-acetyl-LTE4 and LTB4 was also observed in hepatocytes isolated after clofibrate treatment. Our results indicate that peroxisomes play a major role in the beta-oxidation of leukotrienes from the omega-end. Whereas omega-carboxy-LTB4 was beta-oxidized both in isolated peroxisomes and mitochondria, the cysteinyl leukotriene omega-carboxy-N-acetyl LTE4 was exclusively degraded in peroxisomes. PMID- 1761572 TI - Arterial lumican. Properties of a corneal-type keratan sulfate proteoglycan from bovine aorta. AB - A glycoprotein reactive with antibodies against corneal keratan sulfate proteoglycan (KSPG) was purified 300-fold from extracts of bovine aorta using DEAE ion-exchange, gel-filtration, hydrophobic interaction, and reverse-phase chromatographic separations. The intact glycoprotein was 70-80 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Deglycosylation with endo beta-galactosidase and N-glycanase reduced the size to 48 and 37 kDa, respectively, similar to the large isoforms of corneal KSPG. N-terminal amino acid sequence of the arterial KSPG was identical with lumican, the 37B isoform of corneal KSPG, and the arterial KSPG reacted with an antibody to synthetic peptide duplicating this sequence. Arterial KSPG and corneal lumican displayed identical tryptic maps. Arterial lumican contains fucose and mannose in amounts similar to corneal KSPG, but galactose, glucosamine, and sulfate were reduced compared to KSPG from cornea. Treatment of arterial lumican with endo-beta-galactosidase released 8-9 mol of glucosamine and galactose per mol of protein as oligosaccharides. These eluted as neutral, nonsulfated oligosaccharides on high pH anion-exchange chromatography. The size of arterial lumican was not altered by glycosidases having specificity for sulfated keratan sulfate, nor was the charge of the lumican molecule altered by digestion with endo-beta-galactosidase. These data show arterial lumican to be a glycoprotein containing unsulfated lactosaminoglycan chains. Abundance of low sulfate lumican in many tissues indicates that this protein occurs predominantly as a glycoprotein rather than as the more widely studied, highly sulfated proteoglycan present in the cornea. PMID- 1761573 TI - Expression of interferon-beta during the triggering phase of macrophage cytocidal activation. Evidence for an autocrine/paracrine role in the regulation of this state. AB - The expression of cytocidal activity is induced by the sequential interaction of macrophages with a priming stimulus, such as interferon (IFN)alpha, -beta, or gamma, and a triggering stimulus, such as poly(I.C) or lipopolysaccharide. However, most triggering stimuli are also capable of inducing IFN expression. This suggested to us the possibility that in addition to its role in initially priming macrophages for cytocidal activity, IFN may also be expressed during the triggering stage where it may potentially contribute to the regulation of cytocidal activity. We have explored this question by (i) attempting to dissociate IFN-inducing activity from triggering activity with a variety of structurally related and charge-related polyanions; (ii) determining if macrophages express IFN during the triggering stage; and (iii) questioning if IFN produced during the triggering stage contributes to the regulation of cytocidal activation. Exposure of unprimed macrophages to a triggering concentration of poly(I.C) alone failed to induce IFN beta expression. However, exposure of IFN beta-primed cells to poly(I.C) dramatically increased the expression of IFN beta mRNA. Priming with IFN gamma was likewise found to increase the expression of IFN beta mRNA in response to a triggering concentration of polyribonucleotides. Three approaches were adopted to ascertain if the increased expression of IFN beta contributed to cytocidal activation. First, macrophages derived from strains of mice which differ in their susceptibility to IFN induction by poly(I.C) were primed with IFN beta, washed, and triggered with poly(I.C). Under these conditions, macrophages derived from stain B10.A(2R), which are hyporesponsive to poly(I.C) in terms of IFN induction, also showed a diminished capacity to express Bf, a marker of cytocidal activation. Second, exposure of IFN-primed macrophages to poly(I.C) in the presence of anti-IFN alpha/beta antibody was found to reduce substantially the synthesis of NO2/NO3, an alternative marker of macrophage cytocidal activation. Third, exposure of IFN-primed macrophages to the calcium ionophores ionomycin or A23187, which do not induce the production of IFN beta during triggering, led to an abbreviated expression of Bf compared with stimuli that induce IFN beta expression such as poly(I.C). However, the capacity to synthesize Bf in response to A23187 was partially reconstituted when macrophages were triggered with the ionophore in the continuous presence of IFN beta. Collectively, these data show that IFN beta is expressed during the triggering stage of macrophage cytocidal activation and suggest that it plays an important and previously unsuspected role in the expression of this state. PMID- 1761574 TI - 1,25-Dihydroxyvitamin D3 down-regulates aggrecan proteoglycan expression in immortalized rat chondrocytes through a post-transcriptional mechanism. AB - We have examined the effects of various analogs of vitamin D on the expression of the aggrecan proteoglycan by an immortalized rat chondrocyte cell line. The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), produced a concentration-dependent reduction in the synthesis of aggrecan as monitored by histochemical staining of the matrix, incorporation of [35S]sulfate, and the level of aggrecan core protein. Other analogs of vitamin D were much less potent or had no activity whatsoever. The reduced expression of aggrecan was caused by a dramatic decrease in the steady-state level of the mRNA coding for the aggrecan core protein. A nuclear run-off analysis revealed that the rate of transcription of the aggrecan gene was not significantly altered by 1,25(OH)2D3 treatment, suggesting that the metabolite was acting through a post-transcriptional mechanism. Experiments using the transcriptional inhibitor actinomycin D also supported a nondirect effect of 1,25(OH)2D3 on the expression of the aggrecan gene. These results suggest that the vitamin D metabolite activates a new pattern of gene expression which results in a more rapid turnover of the aggrecan mRNA. This system should be useful for characterizing the regulation of chondrocyte gene expression by vitamin D. PMID- 1761575 TI - Purification of the sodium- and chloride-coupled glycine transporter from central nervous system. AB - We have recently developed a reconstitution assay which allows the rapid determination of sodium- and chloride-dependent glycine transport activity of many fractions (Lopez-Corcuera, B., and Aragon, C. (1989) Eur. J. Biochem. 181, 519-524). In this paper we report the purification of the sodium- and chloride coupled glycine transporter from pig brain stem. Transporter is solubilized from plasma membrane vesicles with 2% cholate and purified by sequential chromatography on phenyl-Sepharose, wheat germ agglutinin-Sepharose, and hydroxylapatite columns, followed by a 5-20% sucrose density gradient fractionation. Taking into account the inactivation suffered by the transporter, a final increase in specific activity of about 450-fold is achieved. Although two polypeptides with apparent molecular masses of 100 and 37 kDa are progressively enriched during the chromatographic steps, only the 100-kDa band comigrates with transport activity along the density gradient. This band is finally isolated to apparent homogeneity in the active fractions. We conclude that the 100-kDa band represents the glycine transporter. Finally, the pure transporter can be reconstituted into liposomes, retaining the absolute dependence on sodium and chloride gradients, the electrogenicity, the glycine affinity, the substrate specificity, and the sensitivity to group-selective modifiers characteristic of the native transporter. PMID- 1761576 TI - Guanine nucleotide biosynthesis is regulated by the cellular p53 concentration. AB - As an approach to defining the role of p53 in cellular proliferation, murine cell lines were derived which contain a stably transfected temperature-inducible p53 expression system. Cell lines derived with the system exhibited a 3-6-fold physiologic elevation in the cellular p53 concentration when grown at 32.5 degrees C. A p53 induction phenotype was defined by examination of the growth properties of these lines at 32.5 degrees C. The induction phenotype had three main features: 1) a 2-4-fold increase in doubling time and biphasic growth kinetics; 2) delayed early S phase transit; and 3) complete reversibility either by growth at 37 degrees C or by growth in the presence of added hypoxanthine or xanthosine. The reversal of the induction phenotype by these purine salvage precursors implicated the purine nucleotide biosynthetic pathway as the cellular target for the antiproliferative action of p53. Subsequent genetic and biochemical analyses identified a p53 induction-related purine pathway defect which was localized to the step of inosine 5'-monophosphate conversion to xanthosine 5'-monophosphate. This enzymatic step catalyzed by inosine 5' monophosphate dehydrogenase (EC 1.2.1.14) is the rate-limiting step for GTP synthesis. Extracts from p53-inducible cells growing at the induction temperature show a specific reduction in inosine 5'-monophosphate dehydrogenase enzymatic activity. These findings define p53 as a cellular regulator of the synthesis of GTP, a key regulatory nucleotide for many important cellular processes. Moreover, observations of the growth behavior of p53-inducible cells suggest that by regulating the production of GTP, p53 can control cellular quiescence. PMID- 1761577 TI - Purification and functional characterization of a DNA-binding protein that interacts with a negative element in the mouse alpha 1(I) collagen promoter. AB - In an effort to understand the regulation of expression of the mouse type I collagen genes, we have purified to homogeneity a transcription factor, called inhibitory factor 2 (IF-2), that binds to the mouse alpha 1(I) collagen promoter upstream of the proximal CCAAT motif. IF-2 was purified to homogeneity from mouse lymphocyte nuclear extracts by ion-exchange chromatography and two different steps of DNA affinity chromatography, one using the wild-type IF-2-binding site as affinity ligand and one using a mutated IF-2-binding site that has a higher affinity for the factor. Renaturation of active DNA-binding proteins purified through several chromatography steps from sodium dodecyl sulfate-polyacrylamide gels identified two polypeptides of 120 and 100 kDa, respectively, capable of binding specifically to an IF-2-binding site. DNA transfection experiments of NIH 3T3 fibroblasts using an alpha 1(I) promoter-CAT chimeric gene in which mutations were introduced that either improved or decreased the binding affinity of IF-2 for its recognition site, strongly suggest that IF-2 acts as a transcriptional inhibitor of the mouse alpha 1(I) collagen gene. DNA-binding studies with similar concentrations of purified IF-2 and CBF (CCAAT-binding factor) indicate that CBF inhibits binding of IF-2, whereas IF-2 inhibits CBF binding more weakly. PMID- 1761578 TI - Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages. AB - Cholesteryl ester-loaded macrophages, or foam cells, are a prominent feature of atherosclerotic lesions. Low density lipoprotein (LDL) receptor-mediated endocytosis of native LDL is a relatively poor inducer of macrophage cholesteryl ester accumulation. However, the data herein show that in the presence of a very small amount of sphingomyelinase, LDL receptor-mediated endocytosis of 125I-LDL was enhanced and led to a 2-6-fold increase in 125I-LDL degradation and up to a 10-fold increase in cholesteryl ester accumulation in macrophages. The enhanced lipoprotein uptake and cholesterol esterification was seen after only approximately 12% hydrolysis of LDL phospholipids, was specific for sphingomyelin hydrolysis, and appeared to be related to the formation of fused or aggregated spherical particles up to 100 nm in diameter. Sphingomyelinase-treated LDL was bound by the macrophage LDL receptor. However, when unlabeled acetyl-LDL, a scavenger receptor ligand, was present during or after sphingomyelinase treatment of 125I-LDL, 125I-LDL binding and degradation were enhanced further through the formation of LDL-acetyl-LDL mixed aggregates. Experiments with cytochalasin D suggested that endocytosis, not phagocytosis, was involved in internalization of sphingomyelinase-treated LDL. Nonetheless, the sphingomyelinase effect on LDL uptake was macrophage-specific. These data illustrate that LDL receptor-mediated endocytosis of fused LDL particles can lead to foam cell formation in cultured macrophages. Furthermore, since both LDL and sphingomyelinase are present in atherosclerotic lesions and since some lesion LDL probably is fused or aggregated, there is a possibility that sphingomyelinase-treated LDL is a physiologically important atherogenic lipoprotein. PMID- 1761579 TI - The density and strength of proteoglycan-proteoglycan interaction sites in concentrated solutions. AB - Rheological flow properties of link-stable and link-free proteoglycan (PG) aggregates in concentrated solutions were measured using a cone-on-plate viscometer. A second-order constitutive model, based upon the statistical-network theories of Lodge, [Rheol. Acta 7, 379-392 (1968)] and De Kee and Carreau [J. Non Newtonian Fluid Mech. 6, 127-143 (1979)], was developed to describe the measured steady and transient flow responses exhibited by the PG solutions. Our measurements confirmed previous experimental findings that the complex shear modulus of PG solutions depends on the frequency of the imposed small-amplitude oscillatory shear, and the apparent viscosity and primary normal-stress difference depend nonlinearly on the shear rate under steady-shear flow conditions [Mow et al., J. Biomechanics 17, 325-338 (1984b); Hardingham et al., J. orthop. Res. 5, 36-46 (1987)]. In the present study, we found that PG solutions exhibit pronounced stress overshoot responses and large hysteresis loop effects. These transient responses were shown to be sensitive to acceleration strain (i.e. the second rate of strain) as well as PG structure (i.e. link protein stabilization). The model parameters were determined by curvefitting of the second-order constitutive model and experimental data from steady, oscillatory and transient shear flow measurements. Using this network model, we calculated the density of the idealized interaction sites existing in the PG network, and the average strength of these interaction sites. The results indicate that link-protein stabilization of PG aggregates does not change the density of interaction sites formed in the PG network, rather, it increases the average strength of these interaction sites. PMID- 1761580 TI - Articular contact in a three-dimensional model of the knee. AB - This study is aimed at the analysis of articular contact in a three-dimensional mathematical model of the human knee-joint. In particular the effect of articular contact on the passive motion characteristics is assessed in relation to experimentally obtained joint kinematics. Two basically different mathematical contact descriptions were compared for this purpose. One description was for rigid contact and one for deformable contact. The description of deformable contact is based on a simplified theory for contact of a thin elastic layer on a rigid foundation. The articular cartilage was described either as a linear elastic material or as a non-linear elastic material. The contact descriptions were introduced in a mathematical model of the knee. The locations of the ligament insertions and the geometry of the articular surfaces were obtained from a joint specimen of which experimentally determined kinematic data were available, and were used as input for the model. The ligaments were described by non-linear elastic line elements. The mechanical properties of the ligaments and the articular cartilage were derived from literature data. Parametric model evaluations showed that, relative to rigid articular contact, the incorporation of deformable contact did not alter the motion characteristics in a qualitative sense, and that the quantitative changes were small. Variation of the elasticity of the elastic layer revealed that decreasing the surface stiffness caused the ligaments to relax and, as a consequence, increased the joint laxity, particularly for axial rotation. The difference between the linear and the non linear deformable contact in the knee model was very small for moderate loading conditions. The motion characteristics simulated with the knee model compared very well with the experiments. It is concluded that for simulation of the passive motion characteristics of the knee, the simplified description for contact of a thin linear elastic layer on a rigid foundation is a valid approach when aiming at the study of the motion characteristics for moderate loading conditions. With deformable contact in the knee model, geometric conformity between the surfaces can be modelled as opposed to rigid contact which assumed only point contact. PMID- 1761581 TI - A three-dimensional non-linear finite element study of the effect of cement prosthesis debonding in cemented femoral total hip components. AB - A three-dimensional non-linear finite element analysis of a cemented femoral component in which the component was partially debonded from the cement mantle was used to assess the effects of debonding on stresses in the cement. Three cases of partial cement-metal debonding were modelled with debonding of the proximal portion of the implant down to a horizontal plane which was 35, 62.5, or 82.5 mm below the prosthesis collar. Each situation was studied under loads simulating both gait and stairclimbing. Also, complete debonding between the implant and the surrounding cement mantle was modeled for loads simulating gait. Under stair climbing loads with partial cement-mental debonding, hoop stresses of 13-18 MPa were observed in the cement at the cement-metal interface at the proximal postero-medial corner of the implant. Similarly, in stair climbing, the maximum principal stresses in the cement were also adjacent to the proximal postero-medial region of the implant. These stresses were compressive and increased from 15 MPa with fully bonded interfaces to 48 MPa with debonding down to 82.5 mm below the prosthesis collar. Under gait loads, complete debonding caused high compressive stresses up to 34.9 MPa in the cement distal to the prosthesis tip. Thus, cement failure subsequent to prosthesis debonding is likely in the proximal region in a partially debonded implant due to stair climbing loads and is likely below the prosthesis tip in a fully debonded implant due to gait loading. PMID- 1761582 TI - Physical and mechanical properties of calf lumbosacral trabecular bone. AB - The physical and mechanical properties of calf lumbar and sacral trabecular bone were determined and compared with those of human trabecular bone. The mean tissue density (1.66 +/- 0.12 g cm-3), equivalent mineral density (169 +/- 36 mg cm-3), apparent density (453 +/- 89 mg cm-3), ash density (194 +/- 59 mg cm-3), ash content (0.6 +/- 0.05%), compressive strength (7.1 +/- 3.0 MPa) and compressive modulus (173 +/- 97 MPa) of calf trabecular bone are similar to those of young human. There were moderate, positive linear correlations between apparent density and equivalent mineral density, ash density, and compressive strength; and between compressive strength and equivalent mineral density (R2 ranging from 0.35 to 0.48, p less than 0.001). Apparent density, ash density, and equivalent mineral density did not differ significantly in different regions. In contrast to humans, the compressive strength increased from posterior, near the facet, to the anterior vertebral body. These comparisons of physical and mechanical properties, as well as anatomical comparisons by others, indicate that the calf spine is a good model of the young non-osteoporotic human spine and thus useful for the testing of spinal instrumentation. PMID- 1761583 TI - Mathematical modelling of flow through an irregular arterial stenosis. AB - A mathematical model of flow through an irregular arterial stenosis is developed. The model is two-dimensional and axi-symmetric with the stenosis outline obtained from a three-dimensional casting of a mildly stenosed artery. Agreement between modelled and experimental pressure drops (obtained from an axi-symmetric machined stenosis with the same profile) is excellent. Results are also obtained for a smooth stenosis model, similar to that used for most mathematical modelling studies. This model overestimates the pressure drop across the stenosis, as well as the wall shear stress and separation Reynolds number. Also, the smooth model predicts one instead of three recirculation zones present in the irregular model. The original stenosis is modified to increase the severity from 48 and 87% areal occlusion, while maintaining the same general shape. This has the effect of increasing the pressure drop by an order of magnitude and decreasing the number of recirculation zones to one, with a lower separation Reynolds number. PMID- 1761584 TI - The influence of limb alignment on the gait of above-knee amputees. AB - Biomechanical gait tests on above-knee amputees were conducted in which the alignment of the prosthesis was changed systematically. An eight-segment biomechanical model of the above-knee amputee was developed to analyse and present the three-dimensional kinematic and kinetic data obtained. The effects of alignment changes on the above-knee amputees' gait were studied in terms of the angular displacements of the lower limbs, ground reactions and intersegmental moments. It was found that following the alignment changes the angular displacement at the hip joint on the prosthetic side showed compensatory actions by the amputee. The ground reaction force was sensitive to alignment changes, and in particular, the changes in the characteristics of the fore-aft component of the ground force could be related to the alignment changes. The antero-posterior intersegmental moments at the prosthetic ankle and knee joints were evidently influenced by alignment. PMID- 1761585 TI - Optimal distance from the implement to the axis of rotation in hammer and discus throws. AB - It is a well-known fact that a dramatic improvement in the range of any projective throw can be achieved by increasing the release velocity. In this paper a simple model of a competitor with an implement (hammer or discus) in the turns is considered. The thrower is regarded as a rigid body, and the implement as a point mass. The transverse velocity component of the implement at the release moment is maximized. For finding the optimal distance of the implement from the axis of rotation optimal control theory is applied. According to the proposed model, the optimal hammer throwing technique requires constant and maximal distance of the implement from the axis of rotation, followed by the rapid shortening of the distance immediately prior to the release. In the discus throw, however, this shortening is useless. PMID- 1761586 TI - [Early prognostic factors of the surgery of aneurysms of the abdominal aorta with renal artery clamping]. AB - The aneurysms of the abdominal aorta requiring suprarenal clamping are rare. Suprarenal clamping was required for only 43 of 544 aneurysms operated electively from 1981 to 1989. Twenty-five patients had a juxtarenal aneurysm, without any normal aortic segment under the renal arteries, and suprarenal clamping was therefore necessary while the upper anastomosis was being established (group I). Eighteen patients had an aneurysm enclosing the root of at least one renal artery (group II). Several prognostic factors have been assessed: patient's age, presence of preoperative renal insufficiency, of arterial hypertension or of coronary insufficiency, and revascularization method. Five patients died. Four of them belonged to group II and were over 75 years old. All presented with a preoperative renal insufficiency. Two of these deaths were caused by mesenteric infarction. Four cases of regressive postoperative renal insufficiency were observed in patients for whom renal clamping had lasted longer than 45 minutes. This study allowed outlining three prognostic factors: the patient's age, preoperative renal insufficiency, a period of renal ischemia exceeding 40 minutes. On the other hand, the severity of hypertension had no predictive value. Coronary insufficiency requires a strict hemodynamic surveillance, but is not a contraindication for revascularization. PMID- 1761587 TI - [Cholelithiasis in patients over 75 years of age. Apropos of 147 cases]. AB - The authors perform a retrospective study of a series of 147 patients aged 75 and more, who were treated for gallstone. AMong them, 104 had conventional surgery and 43 a nonsurgical treatment. The noticeable elements produced by this analysis are: the frequency of common bile duct lithiasis and of severe septic complication in elderly patients, the frequency of previous gallstone, sometimes remote in time, a significantly higher mortality when the treatment is non surgical (p less than 0.001), mainly due to the septic complications of the lithiasis. the influence of the diathesis on mortality, and finally, the greater inocuity of the right infracostal approach in view of respiratory complications. PMID- 1761588 TI - [Role of total thyroidectomy in the treatment of multinodular goiter]. AB - Although it may seem to be excessive, total thyroidectomy has recently been advocated by several authors for the treatment of diffuse multiheteronodular goiters. As a complement to a recent study on the thyroid function following thyroidectomy for benign goiters, the authors specify the role of this surgical technique, which had been reserved for the sole thyroid neoplasms for a long time. On the occasion of the presentation of a series of 75 cases gathered from 1989 to 1990, the justification of glandular resection is based on the publication of new pathogenetic data and on the absence of any increase in morbidity, subject to precise indications and to a strict technique aimed at preserving recurrents and locating the parathyroid glands while maintaining their vasculature. When aimed at reducing the frequency of recurrence of euthyroid and toxic diffuse multinodular goiters, total thyroidectomy might also contribute in reducing the morbidity of second surgery, at the expense of a permanent substitution therapy. While the choice of its indications must remain eclecty, thelong-term consequences of initial surgery with too restricted glandular exeresis must be recognized. PMID- 1761589 TI - [Pelvic endometriosis with urinary and digestive involvement. Apropos of 7 cases]. AB - Seven cases of pelvic endometriosis of the urinary or digestive tracts are reported: 4 cases of vesical endometriosis, 1 case of ureteral involvement, 1 rectal case and 1 sigmoid location. The authors point out the difficulty of the clinical preoperative diagnosis--in despite of cyclic troubles--and underline the interest of complementary explorations performed at the time of periods: ultrasound, cystoscopy, rectosigmoidoscopy and coelioscopy. The MR imaging, showing high intensity a T1-weighted images and prominent high intensity on T2 weighted images, is very suggestive of an endometrial lesions. A joint medical and surgical treatment is required. Endoscopic excision, endoprothetic tube, excision-suture, resection-anastomosis and a complementary medical treatment using Danazol, Decapeptyl or progestational agents have to be proposed. Per operative microscopy is advised as routine procedure in order to avoid excessive surgery. PMID- 1761590 TI - [Sigmoido-uterine fistula of diverticular origin. Review of the literature apropos of a case]. AB - The authors report one case of sigmoid-uterine fistula of diverticular origin with a favorable outcome after an ideal colectomy associated with subtotal hysterectomy. They emphasize the rarity of this complication, due to the resistance of the uterine tissue. Its diagnosis is primarily clinical, and other examinations are required only to establish the etiological diagnosis. Surgery must be curative, ideally in one stage including the treatment of the diverticular disease and that of its gynecological consequences, which may vary according to the local conditions. PMID- 1761591 TI - [Synovial cyst of the hip with revealing neurologic symptoms]. AB - The authors report an exceptional case of a ganglion cyst of the hip revelated by sciatica. They recall the usual clinical expression of this pathology, her diagnostic tests and her treatment. They open the discussion about ganglion cyst and mucoid pseudocyts. PMID- 1761592 TI - [Protocol for the use of Pavlik harness in the treatment of congenital dislocation and dysplasia of the hip]. AB - The authors wanted to establish a protocol of use of Pavlik's harness and check ots efficiency with as few complications as possible for the ambulatory treatment of congenital dislocation and dysplasia of the hip. To achieve this, they studied 41 hips in 37 children. They noted 2 failures of reduction, 2 failures of stabilization, 2 cases of osteochondritis and 1 transitory crural paresis. It should be noted that reduction failed and osteochondritis and crural paresis occurred in one and the same child. The other children, ie. 36 hips, had a quite favorable evolution without any stay in hospital, and reduction and stabilization were permanent. This confirms the merits of Pavlik's harness and the low rate of iatrogenic complications. The authors propose a starting, observation and termination procedure for the treatment. However, it still is difficult to define how long stabilization will take and to specify the indication for the treatment of a possible residual dysplasia. PMID- 1761593 TI - [Association of bronchogenic cyst of the pancreas and duplication cyst of the stomach]. AB - One case of bronchogenic cyst of the pancreas associated to a true gastric cyst produced by duplication is described. Such congenital neoformations are extremely rare. The symptoms are highly variable. The diagnosis can be established only through the histopathological study of the surgical specimen. PMID- 1761594 TI - [Cutaneous fistula of hydatid cyst of the liver]. AB - We report a case of liver hydatic cyst fistulised spontaneously at the skin. It is an extremely scarce complication. PMID- 1761595 TI - [Differentiated thyroid cancer on the thyroglossal duct]. AB - Over one hundred cases of carcinomas located on the thyroglossal duct have been reported worldwide. Most of these tumors originally were differentiated thyroid cancers. Their biological behavior is the same as that of tumors of the thyroid gland itself. On the basis of one case discovered in an 11-year-old girl, who presented with regional and systemic metastases, we discuss the various aspects of their origin, diagnosis and treatment. As far as the latter is concerned, we think that these tumors can not always be treated by exeresis of the thyroglossal duct. On the basis of the analysis of situations in which these tumors may be encountered, we propose a carcinological surgery, which might possibly be more aggressive, on the thyroid and cervical lymphatic tissues. PMID- 1761596 TI - [Gastric villous adenoma. 2 new cases]. AB - Villous adenomas are extremely rare in the stomach. This type of lesion is characterized by its high capacity of malignant degeneration, as well as by its association with other tumors of the gastrointestinal tract. In this regard, we present two cases of villous adenoma of the stomach observed in our hospital, as well as a review of the characteristics of these tumors and of the treatment required. PMID- 1761597 TI - [Experience with a surgical mesh covering a hepatectomy incision]. AB - A polyglycolic acid net (Vicryl) has been applied against the hepatectomy section of 27 patients (14% of all our liver resections) to complete its hemostasis. The indications for the use of this net were: the persistence of blood oozing and/or the necessity to shorten the operation. In one patient suffering from severe coagulopathy, active bleeding continued until the patient died; another patient bled until his blood dyscrasia was corrected. One case of abscess was encountered, and treated through a percutaneous approach. Although the achievement of perfect hemostasis is usual in surgical exeresis of the liver, a minority of patients can present with resistant bleeding of the resection slice, for which packing with a net may prove to be useful. PMID- 1761598 TI - [Mortality in the surgical unit of a general hospital. Study of 27 postoperative deaths among patients operated on during 1990-1492]. AB - This study takes in account all post operative deaths during the year 1990 in one surgical Professorial unit of Lille academic hospital (France). During this year, 1492 consecutive patients underwent surgery. The mean age of deceased patients was 63.7 years. 15 died after emergency procedure and 12 after elective surgery. Lastly 2 patients died without any operation. The most common condition encountered in those cases was oesophageal carcinoma, thereafter gastric or duodenal complicated peptic ulcer, and finally colonic carcinoma and diverticular disease. 13 patients had neoplasia (45%). From a critical point of view, 14 patients died after surgical indication or procedure of questionable legitimacy. The comparison with a similar study conducted five years ago and the analysis of these charts allow us to reaffirm some basic principles of surgery. PMID- 1761599 TI - [Isolated proximal revascularization for double aorto-iliac and femoral lesions]. AB - From 1980 to 1990, 101 limbs were revascularized at the upper level only in 67 patients, while they presented with associated aortoiliac and femoral obstructive lesions. The symptoms disappeared after aortofemoral revascularization in 94% of the limbs operated on for claudication and 80% of those operated on for critic ischemia. Surgery of the deep femoral artery was associated in 51% of all cases. The average time lapse is 58 months. No complementary revascularization was needed in the cases of claudication. Out of the patients operated on for critic ischemia, upper revascularization was insufficient in 8 cases. Two of the operated patients were cured after secondary downstream revascularization (4%). Three operated patients still presented with intermittent claudication (6%), and 3 were amputed due to acute iliac obstruction seen at an advanced stage. As no reliable predictive test is available, we find it justified to carry out only upper revascularisation in most cases and to decide on the need for secondary downstream extension according to the clinical outcome. However, simultaneous revascularization at both levels is required in case of extensive involvement of the deep femoral artery, such as observed in only 5 of the patients operated during the same period. PMID- 1761600 TI - [Rectal cysts and rectal functional disorders after surgical treatment for genital prolapse]. AB - From 1966 to 1984, 417 female patients were operated for genital prolapse in the department of surgical gynecology of the Salpetriere Hospital (Pr Blondon's department). The results of the surgical treatment were studied in the posterior perineum from an anatomical (rectocele) and functional point of view (indiced rectal disorders). This study allows drawing several conclusions: when the context leads to deciding to operate the prolapse through an abdominal approach, it is desirable, in order to reduce the risk of postoperative rectocele, to systematically insert a posterior prosthetic band, which will be tethered as low as possible on the posterior aspect of the vaginal (after a sufficiently low extensive rectovaginal cleaving). The Orr-Loygue rectopexy must remain indicated for rectal prolapse, even more so as it is associated with incontinence. Since this procedure often causes constipation of even more complex exoneration disorders, it must be reserved for prolapse associated to a large rectocele (type IV) or an invalidating dyschezia. PMID- 1761601 TI - [Sandblaster or alumina-coated 316 L stainless steel for implantable material in orthopedic surgery. Study on metacarpal bone of sheep]. AB - We have carried out a study in sheep of the behavior of bone in the presence of two materials, 316 L stainless steel with a surface roughened by sandblasting, and the same type of steel, plasma-coated with alumina. Twelve nails of each type were implanted into the medullary cavities of previously fractured metacarpal bones. The samples were removed after 90 days for six animals and after 180 days for six others. The functional study and the radiographic analysis, as well as the growth of bone around the implants as assessed with a light microscope and with microradiography, did not show any significant difference between both types of temporary implants. PMID- 1761602 TI - [Synchronous colorectal cancers]. AB - The frequency of synchronous colorectal cancers ranges from 1.7 to 9.3% according to the series. The incidence of these cancers has been appreciated in various ways, according to variable diagnostic criteria, especially because some authors have included in situ carcinomas developing on degenerated polyps. A retrospective study of the synchronous cancers operated in our department from January, 1980 to August, 1990 allowed us to assess their frequency and location and to discuss the therapeutic choices. Two hundred and forty-nine patients with cancers of the colon or of the rectum have been operated during that period. Twelve (4.8%) presented with more than one colorectal cancer, all discovered simultaneously. The average age of the patients operated for synchronous cancer was higher that that of those operated of isolate cancer (68.8 years versus 63.3). Two thirds of the synchronous cancers were located in the sigmoid loop or the colon and, in one third of all cases, on non-adjacent segments of the colon. The frequent association of colic adenomatous polyps and of synchronous cancers- in one half of the patients in our series--must raise a discussion on the merits of systematic subtotal, or even total, colectomy in the treatment of synchronous colorectal cancers. This is also true for tumoral sites in 2 different segments of the colon. Segmental colectomy may be advocated in the other cases: cancers located on one segment, polyps located only on the resected segment of the colon, or polyps that can be resected via endoscopy. PMID- 1761603 TI - [Prognostic factors for peritonitis in elderly patients. Multifactorial statistical analysis apropos of 216 cases]. AB - The aim of this paper is to analyse retrospectively the data of our patients over 60 years old who had an acute peritonitis, localized or diffuse, to establish prognostic factors. They were 216 patients, who underwent surgical treatment between 1971 and 1990. We observed 243 variables and its significance using the chi 2 test. We divided our study in two stages: from 1.10.71 to 30.09.80 (group I = 93 patients) and from 1.10.80 to 31.01.90 (group II = 123 patients). Group I was composed by 51 men and 42 women with a mean age of 71.9 +/- 5.3 years. General mortality of this group was 36% (33 patients). Group II corresponded to 55 men and 68 women with a mean age of 74.26 +/- 7.1 years. Mortality was 23% (28 patients). Age, sex and associated clinical disorders were not significant on prognosis, meanwhile the clinical and biological form of presentation were not adequate to establish a severity index. The most common ethiologies were: biliar (24 patients = 26%) in group I and appendicular (41 patients = 32.2%) In group II. Significant factors on mortality rates in group II were: delay between onset of symptoms and surgical treatment (over 96 hs, p less than 0.05), generalized or purulent peritonitis operated after 96 hs from onset of the attack (p less than 0.05) and malignancy (p less than 0.01). PMID- 1761604 TI - [Sacrococcygeal cysts. Is Lord Millar's procedure an alternative to exeresis?]. AB - The benignancy of sacrococcygeal cysts stands in contrast to their morbidity and rate of recurrence. Due to the differences in the results found in the literature and to the lack of recommendations as to the optimal surgical procedure, the authors have reviewed a series of 69 patients with a chronic inflammatory state. The procedure was either exeresis up to the sacrum (37 patients) or Lord Millar's procedure (32 patients). The latter consisted in a limited exeresis of the portals and in the extraction of the hairs with a brush, followed in principle by a weekly depilatory treatment until the wound was closed. The results in the 2 groups have been compared. Sixty-six patients (87%) were controlled after an average of 3.7 years. The shorter stay in hospital of the patients operated with Lord Millar's procedure (4.9 vs. 7.6 days) and the shorter period of inability to work (14 vs. 26 days) demonstrate the socioeconomical advantage of this procedure. Recurrence occurred in 5 of the 31 patients controlled after exeresis (16%) and in 7 of the 29 patients controlled after a Lord Millar's operation (24%), including one in the subgroup of 16 patients who submitted themselves to a regular postoperative epilatory treatment (6%) and 6 in the group of 13 who were not followed up in our clinic (46%). Thus Lord Millar's procedure represents an alternative to exeresis, provided the patient is motivated enough to submit himself to regular postoperative controls. PMID- 1761605 TI - [Pyloric obstruction. Apropos of a new clinical case with this rare pathology]. AB - The authors describe a pyloric obstruction due to a mucosal diaphragm in a 16 months old child. They review the literature, and emphasize on the rare frequency on this affection, the steps of its diagnosis, and its surgical removal. PMID- 1761606 TI - [Interruption of the inferior vena cava by the DIL filter. Experience apropos of 34 cases]. AB - Endocaval filters are often used to prevent pulmonary embolism but they have a number of disadvantages. The DIL filter, made of a memory metal wire, is intended to male up for some of these disadvantages. It acts by modifying the shape of the inferior vena cava, which it filters through its meshed loops. It is inserted percutaneously, causes little trauma, and its release is progressive. However, it requires measuring the caliber of the inferior vena cava. This filter was inserted in thirty-four patients over a period of 13 months. One filter has migrated. No recurrence of pulmonary embolism and no thrombosis of the inferior vena cave occurred. PMID- 1761607 TI - [Intra-abdominal textiloma. Report of a case]. PMID- 1761608 TI - [Isolated listeria monocytogenes liver abscess: suspect diabetes mellitus]. PMID- 1761609 TI - [Angiodysplasia of the small intestine. Surgical resection guided by peroperative enteroscopy]. PMID- 1761610 TI - Selective production of vocalization types in different communication contexts. AB - This study investigates the production of vocalization in adult-infant-toy interactions from 0;4 to 0;11. The hypothesis is that vocalizations are selectively uttered in relationship to their production context. Five infants (two girls, three boys) were intensively studied. Non-segmental acoustic features of vocalizations in four communicative contexts were analysed in relation to the individual infants, in order to reveal individual differences. The data were submitted to discriminant function analysis. Results show that (a) different patterns of non-segmental features characterize sounds produced in different contexts; (b) both inter-subject differences and intra-subject consistency are observed; (c) 'selective production' disappears after 0;9. These results are discussed in relationship to sound-meaning development. PMID- 1761611 TI - Intonational differences between the reduplicative babbling of French- and English-learning infants. AB - The two- and three-syllable reduplicative babbling of five French-learning and five English-learning infants (0;5 to 1;1) was examined in two ways for intonational differences. The first measure was a categorization into one of five categories (RISING, FALLING, RISE-FALL, FALL-RISE, LEVEL) by expert listeners. The second was the fundamental frequency (F0) from the early, middle and late portion of each syllable. Both measures showed significant differences between the two language groups. 65% of the utterances from both groups were classified as either rising of falling. For the French children, these were divided equally into the rising and the falling categories, while 75% of those utterances for the English children were judged to have falling intonation. Proportions of the other three categories were not significantly different by language environment. In both languages, though, three-syllable utterances were more likely to have a complex contour than two-syllable ones. Analysis of the F0 patterns confirmed the perceptual assessment. Several aspects of the target languages help explain these intonational differences in prelinguistic babbling. PMID- 1761612 TI - The mosaic acquisition of grammatical relations. AB - The view that grammatical relations have substantial essence, designated as 'subject' or 'object' has difficulty in accounting for the variety of naturally acquirable grammatical relations. The acquisition of grammatical relations is examined from a theoretical framework, ROLE AND REFERENCE GRAMMAR, in which grammatical relations are decomposed into two separate types of structure: logical (semantic) structure and information (pragmatic) structure. The acquisition of grammatical relations from four languages is compared: (1) the definite accusative suffix and pragmatically motivated word order of Turkish; (2) Kaluli verb agreement, case and focus marking postpositions, and pragmatically motivated word order; (3) Hungarian definite and indefinite verb conjunction; and (4) Italian participial agreement and anaphoric, accusative case pronouns. Two conditions on structures are found to cause difficulty: the neutralization of a semantic or pragmatic distinction by interfering structures (e.g. Kaluli and Italian), and global case marking which forces the child to discover relevant semantic characteristics of both the actor and the undergoer (e.g. Hungarian and Kaluli). Structures that encode semantic or pragmatic distinctions independently are more easily acquired (e.g. Turkish). Piecing together discrete structures in a mosaic fashion, the child can acquire the great variety of grammatical relations that exist in human languages. PMID- 1761613 TI - Mean length of utterance and the acquisition of Irish. AB - One of the most widely used indices of language development is a measure of utterance length in morphemes (MLUm). This study examines the applicability of MLUm to the acquisition of Irish. MLUm was calculated for data from Cian, aged 1; 11-3; 0. Even when an attempt was made to 'assume the maximum' by counting all possible morphemes, the correlation between a morpheme MLU (MLUm) and a word count MLU (MLUw) was very high (0.99). This points to MLUw being as effective a measure of Irish development as MLUm, as well as being easier to apply and more reliable. MLUw was calculated for the two younger children in the study (Eibhlis 1; 4-2; 1 and Eoin 1; 10-2; 6). An examination of the relationship between the three children's MLUw values and their grammatical complexity as measured on ILARSP (the Irish adaptation of LARSP) indicates that MLUw is a useful preliminary index for early development in Irish. However, further data are necessary to check whether MLUw loses its predictive relationship with grammatical complexity after a certain point. The study emphasizes the caution necessary in applying MLU to languages whose acquisition has not hitherto been studied, and underlines the role of MLU as a preliminary measure, which must not be overinterpreted. PMID- 1761614 TI - The acquisition of gender: what Spanish children tell us. AB - Data from an experiment on gender acquisition with 160 Spanish children from four to eleven years of age are presented in this paper. In Spanish there are three possible clues (semantic, morphophonological and syntactic), that speakers can use to determine the gender of a noun and the agreement of other variable elements accompanying it. Items where only one of the clues was present, items where there was a combined effect of two of them in agreement (both were feminine or masculine), and items where clues were in conflict (one masculine and the other feminine) were introduced in the experiment. This experimental manipulation made it possible to test the relative strength of the different types of competing clues. In particular, the aim of the present study was to determine the relative importance of intralinguistic and extralinguistic clues, as evidenced by the ability of Spanish children to recognize the gender of a noun upon hearing it in a particular frame, and consequently, to establish the agreement of other variable elements accompanying it. A procedure similar to that used by Karmiloff Smith (1979) was employed. The results (which are compared with those obtained in other languages) give support to the theoretical view that children pay for more attention to syntactic and morphophonological (intralinguistic) information than to semantic (extralinguistic) information. PMID- 1761615 TI - The status of 'canonical SVO sentences' in French: a developmental study of the on-line processing of dislocated sentences. AB - This on-line study investigates the processing of word order by 30 French children (6;6, 8;6, 10;6) and 10 adults. Its main objective is to show that the privileged status granted to 'canonical SVO sentences' is inadequate to account for the on-line processing of pronominal utterances in spoken French. Using a word monitoring task, we showed that word order (NVN vs NNV): (1) is a significant factor in sentences containing no clitic pronoun; (2) stops being significant when sentences contain either one or two clitic pronouns. These results suggest that processing complexity depends upon co-reference ('linear', 'crossed' or 'embedding') assignment constraints rather than upon word order per se. We conclude that, in French, word-order processing always interacts with acceptability considerations provided by cliticization. PMID- 1761616 TI - 'Can I put--I want a slippers to put on': young children's development of request forms in a code-switching environment. AB - This paper concerns the development of semi-modal want/want to, and modals may, can and could in two Trinidadian children, whose Verb Phrase development was studied in naturalistic settings, between the ages of 2;3 and 4;1, and 2;4 and 4;9. The similarities and differences in development between the two are important for underlining a number of key factors in the acquisition process. Accepting the salience of requests/demands in early child language, the study draws attention to the child's propensity for using the means most readily available to him/her in the input, for expression of this function. Additionally, there is evidence of the child's ability to make stylistic discriminations at a very early age and of the propensity for making semantic distinctions among forms. The study indicates that work on the development of grammatical features is incomplete without consideration of sociolinguistic aspects of usage as integral to grammatical acquisition from the outset. PMID- 1761617 TI - Modified repetition in poems elicited from young children. AB - Attempts were made to elicit poems from 133 children between the ages of 2;3 and 6;11. Seventy-eight of the children produced 606 poems between them. Forty-five per cent of the poems contained the syntactic device of modified repetition: a substitution exercise where a grammatical frame is repeated and the substitution occurs in part of the grammatical frame. This was so despite the fact that modified repetition was not present in the examples that were used to elicit poems from the children. The frequency and types of modified repetition used by the children did not vary much with age. The question of whether children's use of modified repetition in their rhythmical poems has the function of helping them to practise grammatical forms, or whether it is simply one reflection of a general human tendency towards the use of pattern in language, is discussed. PMID- 1761618 TI - Simultaneity in children's narratives: the case of when, while and as. AB - This study examines the use of the co-temporal connectives when, while and as in the elicited narratives of 71 children between 4;10 and 11;11. A group of 26 adults provided comparison data. Subjects were asked to 'tell a story' about each of three sets of story pictures. Analysis of the adult data confirmed a preference for preposed over postposed when clauses and supported the notion of a continuum of simultaneity for when, while and as. The oldest children (like the adults) were more likely to prepose when clauses than were younger children, a finding which suggests that with increasing awareness of the information needs of the listener, children begin to use preposed adverbial clauses as information 'guideposts'. Surprisingly, however, children in general were far more likely than adults to use durative predicates with when clauses and did not use co temporal as - substituting when or while in those contexts in which as appeared in the adult protocols. These two findings are shown to be connected, since aspect in the adult data is differentially distributed with respect to the three connectives. It is hypothesized that for narrative purposes children acquire when before while and while before as, in the order of increasing specificity and constraint, with the determining factor being a convergence of syntax, semantics and information flow. PMID- 1761619 TI - Introducing information in dialogues: forms of introduction chosen by young speakers and the responses elicited from young listeners. AB - Young speakers in dialogue must establish mutual knowledge. Traditionally, researchers have focused on how children used indefinite and definite articles to signal novel and shared information. In this study of 170 children aged seven to thirteen, the form of introduction chosen, whether question or statement, is more significant than the type of article used. No developmental effects on article use emerge, with statement + indefinite always the least common choice. However, young speakers use question introductions significantly less than older children. There is also a developmental interaction between speakers' and listeners' behaviour. Question introduction elicit effective listener responses at all ages, but only twelve-year-olds respond reliably to statements. Unfortunately, young speakers prefer just those forms of introduction to which young listeners are least likely to provide informative feedback. Thus two separate developmental effects appear to combine to hamper young subjects' chances of achieving successful communication in dialogues. PMID- 1761620 TI - On the ability to provide evaluative comments: further explorations of children's narrative competencies. AB - This study investigated the changing functions of evaluative devices in children's narratives. The evaluative devices included (a) references to 'frames of mind', particularly to emotions, (b) character speech, (c) 'hedges', (d) negative qualifiers, and (e) causal connectors. Narratives were elicited from a 24-picture story book. The subjects were three groups of native English-speaking Americans (12 per group): five- and nine-year-old children and college undergraduate students. A quantitative comparison revealed that (i) adults used evaluative devices three times as often as five-year-olds, and two-and-a-half times as often as the nine-year-old children; (ii) adults used significantly more references to 'frames of mind' and 'hedges' than the children; and (iii) whereas five-year-olds used each evaluative type equally often, nine-year-olds and adults used references to 'frames of mind' significantly more than the other four evaluation types. A second analysis, focusing specifically on the discourse functions of references to 'frames of mind' revealed that, early on, this particular device is used to express a local evaluative perspective on particular events, while with increasing age it is used to signal the hierarchial organization of the story events. These findings are discussed with regard to two non-linguistic developmental achievements, the formation of event schemas and the formation of a theory of mind. PMID- 1761621 TI - An historical observation on "why 'mama' and 'papa'?". PMID- 1761622 TI - On the acquisition of negation in Tamil and English. PMID- 1761624 TI - Separation of fluorescent oligosaccharide derivatives by microcolumn techniques based on electrophoresis and liquid chromatography. AB - Various aldose oligosaccharides can be quantitatively derivatized into primary amines for subsequent reaction with fluorogenic reagents, such as 3-(4 carboxybenzoyl)-2-quinolinecarboxaldehyde or 3-benzoyl-2-naphthaldehyde. Capillary electrophoresis (CE) and microcolumn liquid chromatography (LC), coupled with laser-induced fluorescence detection, were evaluated as a means of separating complex oligosaccharide mixtures. Whereas microcolumn LC and open tubular CE appear confined in their utility to relatively small oligosaccharides, unprecedented results were obtained with polyacrylamide gel-filled capillaries on hydrolyzed malto-oligosaccharides and enzymatically degraded samples of chondroitin sulfate and hyaluronic acid. PMID- 1761623 TI - Selected applications of cyclodextrin selectors in capillary electrophoresis. AB - Through the use of alpha-, beta-, gamma- and heptakis(2,6-di-O-methyl)-beta cyclodextrin as stereospecific selectors or electrolyte modifiers, both in capillary zone electrophoresis and isotachophoresis, selected model isomeric compounds (including optical isomers) were resolved. Soluble alkylhydroxyalkylcellulose derivatives were further added to the cyclodextrin modified background electrolytes under study. Their presence was found to be essential, as demonstrated by improvements in both enantioselectivity and separation efficiency. The results obtained in both electrophoretic modes, under optimized conditions, are compared and discussed. PMID- 1761625 TI - Low-cost, high-sensitivity laser-induced fluorescence detection for DNA sequencing by capillary gel electrophoresis. AB - A low cost, 0.75-mW helium neon laser, operating in the green region at 534.5 nm, is used to excite fluorescence from tetramethylrhodamine isothiocyanate-labelled DNA fragments that have been separated by capillary gel electrophoresis. The detection limit (3 sigma) for the dye is 500 ymol [1 yoctomole (1 ymol) = 10(-24) mol] or 300 analyte molecules in capillary zone electrophoresis; the detection limit for labeled primer separated by capillary gel electrophoresis is 2 zmol [1 zeptomole (1 zmol) = 10(-21) mol]. The Richardson-Tabor peak-height encoded sequencing technique is used to prepare DNA sequencing samples. In 6% T, 5% C acrylamide, 7 M urea gels, sequencing rates of 300 bases/hour are produced at an electric field strength of 200 V/cm; unfortunately, the data are plagued by compressions. These compressions are eliminated with addition of 20% formamide to the sequencing gel; the gel runs slowly and sequencing data are generated at a rate of about 70 bases/hour. PMID- 1761626 TI - Capillary electrophoresis of DNA in entangled polymer solutions. AB - Electrophoretic separations of DNA restriction fragments were performed in solutions of hydroxyethylcellulose (HEC) using capillary electrophoresis. Rheological studies confirmed that the entanglement threshold (phi*) for the solution is ca. 0.003 g/ml, in good agreement with theoretical predictions. A mesh size an order of magnitude smaller than that found in agarose gels was calculated using polymer-entanglement theory and was confirmed by electrophoretic measurements. Electrophoretic migration was shown to follow the Ogston regime under most conditions. An approach for obtaining smaller mesh sizes is presented. PMID- 1761627 TI - Capillary zone electrophoresis studies of motilin peptides. Effects of charge, hydrophobicity, secondary structure and length. AB - Motilin is a gut hormone, which is involved in gastrointestinal motility. Capillary electrophoresis studies were made on 24 peptides that are N-terminal, C terminal or internal fragments of motilin. The isoelectric point, total charge and hydrophobicity were calculated for all of the peptides. The effects of buffers and pH on migration time and resolution were studied. These included citrate buffer, pH 2.5; phosphate buffer, pH 7.0 and borate buffer, pH 10.0. A capillary zone electrophoresis method was developed to resolve 14 of the motilin peptides. Secondary structure predictions were made using the Chou-Fasman method. Circular dichroism spectra were collected to confirm presence of alpha-helix in several fragments. Effects of charge, hydrophobicity, secondary structure and length of the motilin fragments on migration time were studied. PMID- 1761628 TI - Fractionation of the human recombinant tissue plasminogen activator (rtPA) glycoforms by high-performance capillary zone electrophoresis and capillary isoelectric focusing. AB - This paper reports the fractionation of recombinant human tissue plasminogen activator (rtPA) glycoforms, a complex mixture to demonstrate the high resolving power of capillary zone electrophoresis (CZE) and capillary isoelectric focusing (cIEF). rtPA is a glycoprotein with a complex carbohydrate structure. The electropherograms and IEF patterns have been discussed in light of the known carbohydrate structures of rtPA. rtPA was treated with neuraminidase which removes the sialic acids from the carbohydrate chains. The desialylated rtPA was analyzed by both CZE and IEF and the results were compared to those of untreated rtPA. The usefulness of CZE and cIEF in the characterization of glycoproteins proteins is also discussed. PMID- 1761629 TI - High-performance capillary electrophoresis of histones. AB - A high-performance capillary electrophoresis (HPCE) system was developed for the fractionation of histones. This system involves electroinjection of the sample and electrophoresis in 0.1 M phosphate buffer (pH 2.5) in a 35 cm x 50 micron I.D. coated capillary. Electrophoresis was accomplished in 9 min, separating a whole histone preparation into its components in the following order of decreasing mobility: (MHP) H3, H1 (major variant), H1 (minor variant), (LHP) H3, (MHP) H2A (major variant), (LHP) H2A, H4, H2B and (MHP) H2A (minor variant), where MHP is the more hydrophobic component and LHP is the less hydrophobic component. This order of separation is very different from that found in acid urea polyacrylamide gel electrophoresis and in reversed-phase high-performance liquid chromatography and, thus, brings the histone biochemist a new dimension for the qualitative analysis of histone samples. PMID- 1761630 TI - Capillary electrophoresis for diagnosis and studies of human disease, particularly metabolic disorders. AB - High-performance capillary electrophoresis (HPCE) has been used in a multicomponent analytical system designed to diagnose and study human diseases, particularly metabolic disorders. Comparative analyses, using HPCE, high performance liquid chromatography (HPLC) and an automated amino acid analyser, were carried out on urine and blood samples from patients with homocystinuria, cystinuria, glutathione synthetase deficiency and adenylosuccinase deficiency. HPCE of the sulphur-containing amino compounds, derivatized with monobromobimane and detected by fluorescence spectroscopy, was a quick and simple alternative to classical amino acid analysis. The detection of the characteristic succinylpurines associated with adenylosuccinase defect was equally well achieved with HPLC and HPCE (absorbance detector). Owing to the possible connection between deficiency of taurine (2-amino-1-ethanesulphonic acid) in the heart and the development of cardiomyopathy and heart failure, a simple HPCE method was developed for the determination of taurine in sub-milligram samples of biopsies of the myocardium. The homologue 3-amino-1-propanesulphonic acid was the internal standard, and derivatives of 9-fluorenylmethyl chloroformate and fluorescence detection were used. It is suggested that the potential of HPCE to analyse small volumes should be exploited in biomedicine and clinical diagnosis to analyse sub milligram samples of tissue biopsies and cells. PMID- 1761631 TI - Determination of thiopental in human serum and plasma by high-performance capillary electrophoresis-micellar electrokinetic chromatography. AB - The quantitation of thiopental in human serum and plasma was investigated using high-performance capillary electrophoresis (HPCE) in a micellar configuration and the results were compared with reversed-phase high-performance liquid chromatography (HPLC). Thiopental and an internal standard (carbamazepine for HPCE and thiamylal for HPLC) were extracted from serum or plasma using pentane and a phosphate buffer (pH 6.4). HPCE analysis took place in a phosphate-borate buffer with 50 mM sodium dodecyl sulphate using an automated instrument and HPLC was performed with a C8 column and a mobile phase of phosphate buffer acetonitrile (65:35, v/v). HPCE and HPLC data from 66 patient samples compared well based on linear regression analysis. However, estimates obtained with the inclusion of the internal standard were lower than those based on the sample peak only. This example allows the elucidation of the advantages of using HPCE as an assay methodology for the therapeutic monitoring of thiopental and other drugs. PMID- 1761632 TI - Determination of small drug molecules by capillary electrophoresis-atmospheric pressure ionization mass spectrometry. AB - Capillary electrophoresis (CE) separations are reported for sulfonamides and benzodiazepines in an uncoated fused-silica capillary. The capillary column exit was connected to a liquid junction-ion spray interface combination coupled to an atmospheric pressure ionization (API) triple quadrupole mass spectrometric (MS) system. On-line UV detection occurred 20 cm from the inlet of the capillary and with the API mass spectrometer (CE-API-MS) after the entire length of the capillary (100 cm). The separations were made using volatile buffers composed of ammonium acetate (15-20 mM) with 15-20% of methanol to facilitate ionization under electrospray conditions. This study showed that the major metabolite of flurazepam in man, N-1-hydroxyethylflurazepam, could be detected and characterized in human urine by CE-UV-MS following the administration of a single oral dose of 30 mg of flurazepam dihydrochloride. The presence of additional flurazepam metabolites in human urine was observed by using the system, suggesting that a combination of UV with MS detection should be useful for metabolic studies. In addition to molecular weight determination of compounds, structural information may be obtained by utilizing online tandem mass spectrometry (CE-UV-MS-MS). This was demonstrated for sulfamethazine where the protonated molecule species was transmitted into the collision cell of the tandem triple quadrupole mass spectrometer. Collision-induced dissociation of the protonated sulfamethazine molecule yielded structural information characteristic of the sulfa drug following the on-column injection of 2 pmol of sulfamethazine. PMID- 1761633 TI - Electrochromatographic solid-phase extraction for determination of cimetidine in serum by micellar electrokinetic capillary chromatography. AB - A highly effective electrochromatographic solid-phase extraction and preconcentration method is reported for the determination of cimetidine in serum in the concentration range 0.233-11.4 micrograms/ml. Preconcentrated samples were determined by micellar electrokinetic capillary chromatography while ranitidine was used as an internal standard. Sample preparation included retention of the analyte on a C18 solid-phase cartridge, followed by elution assisted by an applied voltage of 150 V. From 0.5-ml serum samples, 20-50-microliters aliquots were collected for electrophoretic analysis. Within the studied concentration range, the method was linear and provided adequate precision. PMID- 1761635 TI - LC-MS compatible HPLC separation for xenobiotics and their phase I and phase II metabolites: simultaneous anion exchange and reversed-phase chromatography. AB - Benzene and five of its mammalian metabolites, phenol, phenyl-beta-D-glucuronide, phenylsulfate, phenylmercapturate, and t,t-muconic acid, are separated on a methylstyrene-divinylbenzene-based anion exchange--reversed-phase column. The retention of the model compounds is manipulated by modifying the type, ionic strength, and pH of the mobile phase buffer, and the type and percent of organic mobile phase modifier. The separations developed are compatible with both particle beam (PB) and thermospray (TSP) interfaces used in liquid chromatography mass spectrometry (LC-MS). These separations should be adaptable to the study of a wide range of xenobiotics and their phase I and phase II metabolites, and provide an LC-MS compatible alternative to the use of iron pairing reagents. PMID- 1761634 TI - Influence of operating parameters on reproducibility in capillary electrophoresis. AB - The reproducibility of two migration parameters (retention time and mobility) of a seven-component test mixture was examined under various operating conditions using laboratory-built capillary electrophoresis systems. It was found that the frequency of rinsing the capillary and the solutions used for rinsing had the greatest effect on migration reproducibility. In addition, it was found that the migration behavior of solutes that interact with micelles is not repeatable unless the proper rinse protocol is applied. Inconsistent migration behavior is linked to inconsistent total current of the system. Preliminary investigations indicate that the fluctuation in total current were associated with non equilibrium conditions between the buffer and the capillary wall. PMID- 1761636 TI - The application of solid phase extraction to the analysis of tobacco-specific nitrosamines. AB - A new isolation and separation method has been developed for the alkaloid-related nitrosamines in tobacco, called tobacco-specific nitrosamines (TSNA). The improved isolation procedure involves the extraction by sonication of TSNA from cured tobacco with toluene and an aqueous citrate buffer solution, while purification is achieved by solid phase extraction on small silica cartridges. Interfering extract materials are eluted from the silica cartridges with the toluene and a chloroform-methylene chloride solvent, while subsequent elution with chloroform yields the TSNA in a purified fraction. Gas chromatographic analyses on an SE-54-coated glass capillary column and detection by a nitrogen phosphorous detector produce very good data on the four TSNAs, which include N nitrosanatabine (NATB), N-nitrosoanabasine (NAB), 4-(N-methyl-N-nitrosamino)-1-(3 pyridyl)-1-butanone (called NNK), and N-nitrosonornicotine (NNN). The method is shown to be quantitative, reproducible, and applicable to the determination of TSNA in various tobacco samples, such as stems and lamina of cured tobacco leaves, as well as to smokeless tobacco. PMID- 1761637 TI - Ion chromatographic determination of inositol tris- and tetrakisphosphates in rat brain. AB - Ion chromatography has been applied to the determination of inositol 2,4,5 trisphosphate (Ins 2,4,5-P3), inositol 1,3,4-trisphosphate (Ins 1,3,4-P3), inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), and inositol 1,3,4,5 tetrakisphosphate (Ins 1,3,4,5-P4). Other common polyanionic metabolites, including ATP and GTP, do not interfere with the determinations even at concentrations exceeding those normally found in tissue extracts. Assay of rat brain for Ins 1,4,5-P3 and Ins 1,3,4,5-P4 by the method of standard addition gives values which are within 10% of the amount calculated by external calibration. When rat brain homogenates are spiked with Ins 1,4,5-P3, the recoveries are greater than 90%. Treatment of animals with lithium chloride and pilocarpine produces increases in total inositol trisphosphates from 14 to 64 nMol/g wet weight, and increases in Ins 1,3,4,5-P4 from 0.9 to 18 nMol/g wet weight in tissue extracts obtained from the cerebral cortex. Using chemically suppressed conductivity, detection limits in brain are estimated to be 50 pMol/g wet weight for inositol trisphosphates and 22 pMol/g wet weight for inositol tetrakisphosphate. PMID- 1761638 TI - Effect of column and mobile phase modifications on retention behavior in size exclusion chromatography of polycyclic aromatic hydrocarbons on poly(divinylbenzene). AB - Results are reported from a study, the goal of which was the reduction of the nonsize effects that govern the size exclusion chromatography (SEC) of planar polycyclic aromatic hydrocarbons (PAHs) on poly(divinylbenzene) (PDVB). Thought to arise from electron-pair donor--electron-pair acceptor (EPD-EPA) interactions between column packing and PAH eluate, nonsize effects could be substantially reduced by the addition of bulky substituents to the PAH, thereby perturbing EPD EPA interactions between column and eluate. In this work we study the effect of adding a bulky substituent to the column material itself and have selected a sulfonated column material for this purpose. The-SO2OH group provides considerable steric shielding of the PDVB phenyl groups from the PAH eluates and thus its presence could weaken column-eluate interactions, but it is also electron-withdrawing and could possibly aggravate nonsize behavior, because the electron-pair acceptor strength of PDVB could be increased by electron withdrawing substituents. It was found that either an increase or decrease of EPD EPA bonding could result with the sulfonated PDVB (S-PDVB) columns, depending on the nature of the mobile phase. Size-dependent elution of PAHs could be obtained with S-PDVB for two classes of PAH by the inclusion of a small amount of hydrogen bonding solvent, i.e. methanol, to the mobile phase. It is thought that the methanol additive, by strongly hydrogen bonding with the S-PDVB sulfonic acid groups, provides the additional steric shielding necessary to minimize EPD-EPA interactions. PMID- 1761639 TI - Elevated monocyte interleukin-6 (IL-6) production in immunosppressed trauma patients. II. Downregulation by IL-4. AB - Aberrant monocyte mediator production is pivotal in the development of posttrauma immunosuppression. We have previously shown that immunodepressed trauma patients' monocytes produce elevated interleukin-6, suggesting their in vivo preactivation. This study confirms that preactivated patients' Mo produce greater levels of IL-6 than normals' Mo to the same in the in vitro Fc gamma RI stimulation. We also demonstrate the capacity of interleukin-4 to downregulate the elevated interleukin-6 production of trauma patients' in vivo preactivated monocytes. Monocyte interleukin-6 downregulation by interleukin-4 is dose dependent and occurs whether Fc gamma RI cross-linking, muramyl dipeptide, indomethacin plus muramyl dipeptide, or interferon-gamma plus muramyl dipeptide is the interleukin 6 inducing stimulus. Furthermore, interleukin-4-dependent downregulation of monocyte interleukin-6 expression is confirmed at both the supernatant and the mRNA levels. Simultaneous downregulation of posttrauma elevated monokines implies a possible therapeutic benefit of interleukin-4 for trauma patients. PMID- 1761640 TI - Subset markers of CD8(+) cells and their relation to enhanced cytotoxic T-cell activity during human immunodeficiency virus infection. AB - Using fresh whole blood or isolated lymphocytes, the activity of in vivo generated cytotoxic T-lymphocytes (CTL) was measured as the OKT3-specific lysis of HL-60 targets, in a cross-sectional study of 53 HIV (+) patients. CTL activity in the entire HIV(+) group was two to three times higher than in HIV(-) controls, with WHO stage 3 (=pre-AIDS) patients showing the highest cytolytic function. The whole-blood CTL assay was validated and its practical and theoretical advantages are discussed. Within the CD8(+) cells, the number and proportion of the CD45RO(+) "memory" subset were significantly increased in HIV(+) subjects. The HLA-DR(+) subset rose most spectacularly in the asymptomatic stage of the infection, while the CD38(+) subset was the only one still significantly rising between the pre-AIDS and the AIDS stage. CTL activity was most closely correlated with T8 cells expressing the CD38 marker. In the context of CTL, CD38 thus seems to reflect activation rather than immaturity. Lymphocytes from HIV(+) subjects with a high OKT3-specific lytic capacity also destroyed normal lymphoblasts to a significant extent, pointing to their possible involvement in an autodestructive process. Our data thus suggest the importance of T8 cytolytic function and/or T8 subtyping in the immunopathogenesis and the prognosis of HIV infection. PMID- 1761641 TI - Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease. AB - A child with disseminated disease due to Mycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis of in vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was corrected in vitro by exposure of the patient's monocytes to indomethacin and normal serum. Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement. PMID- 1761642 TI - Treatment of septic thrombocytopenia with immune globulin. AB - Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise; P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures. PMID- 1761644 TI - The biological imagination. PMID- 1761643 TI - Severe combined immune deficiency presenting with cyclic hematopoiesis. AB - At age 2 months a male infant presented with a cyclic clinical syndrome every 14 21 days that included pharyngeal aphthous ulcers, high fever, lymphadenopathy, pallor, and malaise. Serial blood studies indicated cycling of all blood cell elements, compatible with a diagnosis of cyclic hematopoiesis (CH). He also manifested a progressively severe immune deficiency, not described before in human CH. When first studied at age 5 months, he was hypogammaglobulinaemic with normal B lymphocyte numbers. By 6.5 months, he was agammaglobulinaemic. At age 8 months, he developed severe pneumocystis carinii pneumonia, and studies showed a state of severe combined immune deficiency. The patient received a bone marrow transplant from his HLA-identical sister with no preconditioning therapy. Subsequently, normal immune function developed and the cyclic hematopoiesis resolved. The majority of lymphocytes is of donor origin. Persistence of erythrocytes and neutrophils of recipient origin suggests that the hematopoietic stem cells were not abnormal. We speculate that this patient had a primary deficiency of a differentiation factor affecting maturation of lymphoid and myeloid progenitor cells. PMID- 1761645 TI - A quantitative genetic analysis of localized morphology in mandibles of inbred mice using finite element scaling analysis. AB - We analyzed patterns of mandibular genetic and phenotypic morphological integration and the relationship of genealogy to interstrain molecular and morphological differences in ten inbred strains of mice. Positions of mandibular landmarks in two-dimensional space were used to construct a finite element mesh for each individual, then all individuals from the ten strains were compared to the average mandible from a standard strain (SEA/GnJ). Measures of size and shape associated with finite element scaling analysis were then used in a quantitative genetic analysis of mandibular variation. Significant genetic variation for mandibular size and shape was uncovered. Patterns of both genetic and phenotypic correlation for measures of landmark-specific sizes were consistent with models of morphological integration based on the developmental origin of parts of the mandible and on the effects of muscle attachment on mandibular morphology. Shape differences local to particular landmarks did not show these forms of morphological integration. Although interstrain distances based on local shape magnitudes were significantly correlated with genealogical relationship, distances based on local size differences were not. Even higher than the correlation of genealogy with distances based on local shape magnitude was the genealogical-molecular distance correlation. Patterns of morphometric mandibular variation corresponded to expected effects of epigenetic developmental processes. Also, when detailed shape differences were considered, morphology served as a rough guide to genealogy, although molecular distances showed a stronger relationship. PMID- 1761646 TI - Immunohistochemical localization of TGF-B1 during morphogenetic movements of the developing mouse palate. AB - Transforming growth factor-beta (TGF-B1) may play an important role in developmentally active tissues in which it is found in high concentrations. We localized TGF-B1 in the developing fetal mouse palate immunohistochemically using a polyclonal antibody. Mouse fetal palates at 12-17 days (inclusive) of gestation were examined and specific focal concentrations of TGF-B1 identified regions undergoing active morphogenesis. The association of TGF-B1 with aggregates of mesenchymal cells in the palate and chondroblasts, rhabdomyocytes, and epithelia of the craniofacial complex strongly implicates its role in proliferation and differentiation in the developing mouse palate. We believe these findings have important bearing on the normal development of the palate as well as cleft anomalies. PMID- 1761647 TI - Does the tongue play a role in the initial development of vertical palatal shelf in hamster? AB - A study was undertaken to examine whether the tongue plays any role in determining the primordial development of palatal shelves in a vertical direction in mammals. Control and 6-mercaptopurine-treated embryos from Golden Syrian hamsters were examined by scanning electron microscopic and histological techniques for the spatio-temporal relationship of primordial development of the palate, tongue, and mandible. DNA synthesis, measured by 3H-thymidine incorporation, was used as an index of growth. The data indicated that in controls, vertical palate development began in the anterior half from the roof of the oronasal cavity, whereas the tongue bulges and the mandibular process developed in the posterior half of the oronasal cavity. A burst in DNA synthesis occurred in the palate and mandible, but not in the tongue. In 6-mercaptopurine treated fetuses, although the chronological appearance of primordia of all three structures was normal, DNA synthesis was inhibited in all three structures. The recovery in DNA synthesis, albeit partial, was faster in the palate and mandible than in the tongue. On the basis of observations from the present study, along with those from other vertebrates, it is suggested that the developing tongue may not play any role in determining the direction of development of the palatal primordia. PMID- 1761648 TI - Measurement precision and reliability in craniofacial anthropometry: implications and suggestions for clinical applications. AB - Craniofacial anthropometry has become an important tool used by both clinical geneticists and reconstructive surgeons. Yet little attention has been paid to the potentially serious problem of measurement error. This paper examines intra observer measurement error and precision (also called repeatability or reliability) for 52 commonly used anthropometric variables of the head and face. Two factors proved critical to reliability: magnitude of the measurement in question and the degree to which its constituant landmarks could be readily identified. Thus, all of the measurement variables with means above 10 cm proved to have good or excellent reliability. In contrast measurement variables with means below 10 cm were more likely to have poor reliability. This trend was especially evident in variables with means of 6 cm or less where 18 of the 20 variables in this range had poor reliability. The least reliable variables were those like philtrum breadth, columella breadth, and nasal root breadth that combine small magnitude with difficult to define landmarks. While these results suggest that it may be prudent to avoid using craniofacial variables with small dimensions this may be neither practical nor desirable. In such cases repeat measurements may be the best means for optimizing reliability. PMID- 1761649 TI - Heritability of dental arch dimensions in humans. AB - The purposes of this study were to estimate the heritabilities of several human dental arch dimensions and compare the hereditary differences among kinships and among variables. The sample consisted of 102 Japanese families, each including both parents and one of their offspring, and on average all subjects had relatively well-aligned permanent dentitions. The heritabilities of all variables were estimated from the regression of offspring on parent and on midparent. Results showed that genetics played a role regarding dental arch dimensions, and arch perimeter (sum of tooth width) was a more definite genetic-related factor than other arch dimensions, such as width, length, or size. There were few significant hereditary differences between sons and daughters, and between upper and lower arches for each variable. Sex chromosomal involvement was not confirmed, but maternal effects were found to be more evident in daughters than in sons, for both arches. Comparisons among the heritabilities of overall and of anterior arch dimensions indicated that size of the anterior part of the dental arch might be less resistant to environmental factors, especially in case of the lower arch. PMID- 1761650 TI - Developmental stage of the dentition and speech sound production in a series of first-grade schoolchildren. AB - This study was undertaken to investigate the effect of developmental stage of the dentition on speech sound production in children with and without articulatory speech disorders. In the whole sample, there were 281 subjects, mean age 7.5 years (SD 0.4). The stage of the eruption of the permanent incisors was calculated as the percentage height of each tooth of the mean crown height of the corresponding tooth in a group of 252 young adults. Eruptional stage of the first permanent molars was classified into three categories. Articulatory disorders were diagnosed by one experienced speech therapist and phoniatrician using the Remes Articulation Test [Remes, 1975] for the Finnish language. The results showed a wide interindividual variation in developmental stage of the dentition in a group of 7-year-old children with a tendency of the first permanent molars but not the incisors to erupt earlier in girls than in boys. Boys had a higher frequency of misarticulations estimated to need treatment than did girls. The present results indicate that during eruption of permanent teeth it is more important to draw attention to symmetrical eruption and to individual timing pattern rather than to the mean values of tooth eruption in subjects of the same age. The findings also suggest a decreasing risk of faulty speech sound production with advancing eruption of some permanent teeth still present in 7 year-old children. PMID- 1761651 TI - Advanced heterotopic pregnancy after in-vitro fertilization and embryo transfer, with survival of both the babies and the mother. AB - A combination of an extra-uterine and an intra-uterine pregnancy is defined as heterotopic pregnancy. An infertile patient, pregnant at her fourth in-vitro fertilization/embryo transfer attempt, was diagnosed at 21 weeks' gestation as having simultaneous abdominal and intra-uterine pregnancy. Expectant management under strict hospitalization was proposed and accepted by the couple, fetal assessment was by serial ultrasound evaluation of growth and amniotic fluid volume and by non-stress tests. Planned operative delivery was accomplished at 34 weeks' gestation. Both the mother and infants are alive and well. PMID- 1761652 TI - Micromanipulation of gametes using laser microbeams. AB - Various microsurgical procedures at the cellular and subcellular levels using laser non-touch techniques are presented and reviewed. In these procedures, the beams of light, varying in their wavelength (range: 14 ns to continuous wave), were directed via microscopes towards the target area. Micromanipulation of human spermatozoa with a laser-generated optical trap enabled the assessment of possible effects on sperm motility and measurements of the relative force generated by each single spermatozoon. Furthermore, the optical trap also provides a new approach to the measurements of intracellular forces without physically touching the cell or its organelles, and inducing chromosome movement during cell division is also possible. Laser beams in a specific configuration are able to induce minimal superficial damage to the zona pellucida of oocytes from various species. This manipulation is aimed at increasing the fertilization rate following insemination with low-quality spermatozoa. Another intracellular application of the laser beams is the destruction of extra pronuclei in polyspermic fertilized human oocytes. These procedures require special equipment which is not commonly available. However, simpler devices may be developed if the advantages of this novel technology are demonstrated. PMID- 1761653 TI - Premature chromosome condensation as a sign of oocyte immaturity. AB - In this work we report the possibility that oocyte immaturity is associated with premature chromosome condensation (PCC) after in-vitro fertilization (IVF). Using a murine model, we have related PCC and endoreduplicated-like oocytes to oocyte immaturity as a basis for a prognosis in oocyte immaturity problems. The cytogenetic analysis was performed in 511 embryos obtained from immature oocytes that were directly fertilized in vitro and in 1363 embryos obtained from immature oocytes that were matured in vitro with different concentrations of human chorionic gonadotrophin (HCG) added to the culture medium. As a control we used 507 embryos obtained from freshly ovulated oocytes. PCC at the G1-phase-(G1-PCC) was observed only when immature oocytes were immediately fertilized in vitro (45.4%) and PCC at the S-phase (S-PCC) only when using in-vitro matured oocytes with the highest HCG concentration (3.3%). Neither G1-PCC nor S-PCC were found in the control group. Endoreduplicated-like oocytes appeared in a significant percentage (27.3%) only in the immature group. Immature oocytes yielded a low fertilization rate (16.6%) while in-vitro maturation seemed to confer a higher fertilization capacity compared to the control group (90.1% versus 78.2%). The possible correlation between PCC and oocyte immaturity provides new prospects in the determination of human IVF failures of unknown origin. Thus, when a problem of oocyte immaturity is diagnosed through the presence of PCC, a special programme of in vitro oocyte maturation, such as a longer preincubation time or addition of hormones to the media, would be recommended. PMID- 1761654 TI - Vagaries of sperm preparation techniques and fertilization failure in assisted reproductive technology. PMID- 1761655 TI - Ultrasonographic appearance of the endometrium in natural and stimulated in-vitro fertilization cycles and its correlation with outcome. AB - Ultrasonographic evaluation of the endometrium in 56 IVF patients was performed prospectively. Endometrial thickness and pattern were analysed in 18 natural cycle and 38 stimulated-cycle patients. Thickness was measured from the echogenic interface of the endometrium-myometrium junction on a transverse section at the level of the fundus. Patterns were classified as A (homogeneous, hyperechogenic), B (mixed, with an outer hyperechogenic and inner hypoechogenic layer) or C (fluid filled cavum with ring configuration). The thickness and pattern distributions were similar in natural- and stimulated-cycle patients. There was no correlation between thickness and serum oestradiol levels, the diameter of the largest follicle or the pregnancy outcome in either group. However, the occurrence of endometrial pattern A on the day prior to oocyte retrieval had a predictive value of 100% for a non-conceptional cycle. In contrast, pattern B occurred in a significantly greater proportion of pregnant than non-pregnant patients. PMID- 1761656 TI - The effect of progesterone upon first trimester trophoblastic cell differentiation and human chorionic gonadotrophin secretion. AB - The effect of progesterone (P) upon first trimester placental secretion of human chorionic gonadotrophin (HCG) and cellular differentiation was studied using both static and kinetic methods. At 1 microM, P inhibited spontaneous episodic secretion of HCG when given in short pulses (1-4 min) to placental explants in superfusion. Both HCG pulse frequency and amplitude were reduced. At 0.1-0.01 microM P concentrations, the effect of HCG secretion was milder. P also blocked the maximally effective concentration 100 pM of gonadotrophin releasing hormone (GnRH) analogue, a known HCG stimulant, when given together with it for 1 min. This inhibitory effect lasted for 1 h after P administration. Progesterone at 1 microM, added daily for 1 week blocked HCG secretion by isolated trophoblastic cells in static culture. This inhibitory effect lasted until the fifth day. No effect on differentiation and long-term viability was noticed in P-treated cells. Incubation with 0.1-1.0 microM P did not affect HCG secretion by explants after 24 h. In contrast, the effect of 1 microM cortisol or 1 nM oestradiol was stimulatory. In conclusion, P exerts both a rapid and delayed inhibitory effect upon HCG secretion and production. It may do so by counteracting the stimulatory effect of endogenous GnRH on gonadotrophin secretion by the placenta. PMID- 1761657 TI - Hormonal and histological evaluation of the luteal phase after combined GnRH agonist/gonadotrophin treatment for superovulation and luteal phase support in in vitro fertilization. AB - A hormonal and histological study of the luteal phase was performed in 21 stimulated in-vitro fertilization (IVF) patients not undergoing embryo transfer. Ovarian stimulation was carried out with gonadotrophins [follicle stimulating hormone (FSH) + human menopausal gonadotrophin (HMG)] under pituitary suppression with buserelin. Ovulation was induced with 5000 IU human chorionic gonadotrophin (HCG) and additional doses of 5000, 2500 and 2500 IU were given on the day of follicular aspiration, and 2 and 5 days later respectively, to support the luteal phase. Supraphysiological levels of oestradiol (E2) and progesterone in plasma were found in the midluteal phase of all women, while prolactin was in the normal range. An endometrial biopsy taken in the late luteal phase was normal in 90.5% (19/21) of patients, most of them (15/19, 79%) having E2 greater than 1500 pg/ml on the day of HCG. Conversely, both patients with defective endometrial biopsies had E2 levels less than 1500 pg/ml. PMID- 1761658 TI - Comparison of 'poor' responders with 'good' responders using a standard buserelin/human menopausal gonadotrophin regime for in-vitro fertilization. AB - This study identifies a group of 87 patients, who demonstrated a 'poor' response to a standard buserelin/human menopausal gonadotrophin (HMG) regime. The subsequent outcome in 61 of these 'poor' responders when treated with a higher dose of HMG to achieve a satisfactory response was compared with 250 patients, who showed a 'good' response to the standard regime. 'Poor' responders were significantly older than 'good' responders (P less than 0.001), but no significant difference was demonstrated in the indication for in-vitro fertilization (IVF). Even on higher doses of HMG, 'poor' responders took longer for their follicles to achieve maturity than the 'good' responders (P less than 0.01). 'Poor' responders produced 8.9 oocytes per oocyte collection compared to 11.8 in the 'good' responders (P less than 0.01). The fertilization rate was significantly lower in the 'poor' responders compared to the 'good' responders (P less than 0.01). Although there was no significant difference in morphometric grading between 'poor' responder embryos and 'good' responder embryos, the rate of cell division was significantly slower in embryos of the 'poor' responders than the 'good' responders (P less than 0.01). The pregnancy rate per oocyte retrieval was 9% in the 'poor' responders compared to 29% in the 'good' responders (P less than 0.01). The implantation rate in the 'poor' responders was 4.4% compared to 16.1% in the 'good' responders (P less than 0.001). PMID- 1761659 TI - Does ovarian stimulation for in-vitro fertilization induce a hypercoagulable state? AB - Effects on blood coagulation and fibrinolytic activity during ovarian stimulation for in-vitro fertilization (IVF) were examined in 12 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, mean serum oestradiol concentration 0.16 nmol/l) and the day after ovulation induction with human chorionic gonadotrophin (HCG) (days 10-12, mean serum oestradiol concentration 5.35 nmol/l). We measured whole blood clotting time, whole blood clot lysis time, plasma fibrinogen, factor VII and antithrombin III. The whole blood clotting time was slightly, but not significantly shortened after ovarian stimulation. A significant rise in plasma fibrinogen (P less than 0.001) and reduction in antithrombin III (P less than 0.001) were observed, whereas no change in factor VII was found. The blood fibrinolytic activity was significantly reduced as evaluated by an increase in the clot lysis time (P less than 0.02). These results indicate that ovarian stimulation for IVF may create a state of hypercoagulability. PMID- 1761660 TI - Use of the hormonal response to clomiphene citrate as an endocrinological indicator of ovarian ageing. AB - We compared the gonadotrophin and oestradiol responses to clomiphene citrate (CC) in women aged 18-25 versus 35-40 years. Despite similar baseline hormone concentrations and the attainment of similar concentrations of the E and Z isomers of clomiphene, higher follicle stimulating hormone (FSH) concentrations were observed in the older women, possibly indicative of their ageing ovaries. Furthermore, diminished oestradiol responses occurred in a subgroup of women showing FSH hyper-responsiveness to CC. These preliminary results support the concept that the hormonal response to CC may be an indicator of approaching perimenopause. PMID- 1761661 TI - Biochemical monitoring during hormone replacement therapy cycles for transfer of cryopreserved embryos in patients with functional ovaries. AB - Biochemical monitoring was undertaken in 22 treatment cycles for women with normal ovarian function who underwent pituitary suppression with buserelin and administration of exogenous oestradiol (E2) and progesterone (P) for cryopreserved embryo transfer (ET). Eighteen transfers of 1-4 thawed embryos, on the third day of exposure to progesterone, resulted in five clinical pregnancies (27.8%) and one biochemical pregnancy. There was no difference between pregnant and non-pregnant patients in the number and quality of embryos transferred, age, weight or infertility diagnosis. Serum E2 level from days 10-17 (the late proliferative phase) of the therapy cycle were significantly higher in the pregnant group compared with the non-pregnant group (P less than 0.05--P less than 0.005). There were no significant differences in P levels between the two groups from the onset of progesterone administration to the end of the cycle. However, as might be expected, the mean E2/P molar ratio in the pregnant group was significantly higher at the time of ET (P less than 0.02). It is concluded that biochemical monitoring during the embryo replacement cycle is necessary to tailor drug dosages for individual requirements to achieve adequate E2 levels before ET. Alternative routes of oestradiol administration need to be considered in patients with poor E2 profiles. PMID- 1761662 TI - Selective drop-out in successive in-vitro fertilization attempts: the pendulum danger. AB - Success rates from in-vitro fertilization (IVF) in the long term are dependent on selection procedures with regard to continuation into further IVF episodes. Publications on success rates in successive episodes will give incentives to adapt selection criteria, but if these publications do not deal explicitly with patient selection, the adaptations might change their direction every time: the pendulum danger. PMID- 1761663 TI - Beneficial effects of a 24 h delay in human chorionic gonadotrophin administration during in-vitro fertilization treatment cycles. AB - We used a gonadotrophin-releasing hormone agonist (buserelin) and human menopausal gonadotrophin (HMG) for superovulation for in-vitro fertilization (IVF) in 143 patients. The patients were prospectively allocated to two balanced groups. In one group (47 patients) human chorionic gonadotrophin (HCG) was given when the three largest follicles were greater than or equal to 17 mm in diameter, with consistent levels of plasma oestradiol (standard group). In the second group (96 patients), HCG injection was delayed by 24 h (delayed group). In the delayed group of patients, proportionately more had clinical pregnancies (52.1% versus 34.0%). These results suggest that IVF patients will benefit from delayed administration of HCG. The traditional criteria for HCG administration should be changed when buserelin is used. PMID- 1761664 TI - Multiple follicular recruitment and intrauterine insemination outcomes compared by age and diagnosis. AB - We studied the outcome of our intrauterine insemination (IUI) programme, evaluating female age and diagnosis. One-hundred-and-twenty-six patients less than 36 years of age (mean 30.91 +/- 3.02 years) completed 306 cycles of multiple follicular recruitment (MFR) and timed IUI; 64 patients greater than or equal to 36 years of age (mean 38.36 +/- 2.08 years) completed 166 cycles (total 190 patients, 472 cycles). The male partners' semen was prepared for IUI with wash and swim-up techniques. Diagnostic groups were: male factor (n = 26), idiopathic (n = 33), endometriosis (n = 19), ovulatory disorder (n = 7), other (n = 19) and combined factors (n = 86). Pregnancy rates (% per couple, % per cycle) [overall (31.58, 12.7)] [less than 36 years (38.10, 15.69)] [greater than 36 years (18.75, 7.23)] were greater in the less than 36 years group (P less than 0.025). The probability of conception after three treatment cycles was 0.402 overall, 0.481 for age less than 36 years and 0.252 for age greater than or equal to 36 years. The probability of conception for male factor and idiopathic infertility patients was 0.469 and 0.411 respectively. An age effect was found on pregnancy rates in the idiopathic group only. In conclusion, MFR + IUI is a valuable treatment especially for male factor patients and patients less than 36 years old, with idiopathic infertility. PMID- 1761665 TI - The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology. AB - Nineteen European fertility centres participated in a controlled randomized trial aimed at comparing the effectiveness of five methods for the treatment of unexplained infertility. Each centre was invited to employ two of the five treatments being investigated, and the treatment allocated to individual patients was then decided by randomization. The treatments were superovulation alone, and superovulation together with one of the following procedures: intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT), in-vitro fertilization (IVF). All the patients admitted to the study had experienced greater than 36 months infertility prior to the start of the trial, and only patients less than 38 years of age were included in the investigation. Further, the study was confined to patients with normal Fallopian tubes, and where there was evidence of spontaneous ovulation. Yet another prerequisite for inclusion in the study was that the male partner was 'normal' as regards fertility. Due to unavoidable practical difficulties, the experimental design eventually obtained was severely unbalanced. Nevertheless, objective statistical comparisons were possible among the five treatments, using non orthogonal analyses of variance. By the completion of the trial 444 patients had been treated in a total of 649 cycles. There was some statistical evidence that the pregnancy rate obtained from superovulation alone was inferior to that obtained by using superovulation together with one of the methods of assisted conception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761666 TI - Are there predictive criteria of complicated ovarian hyperstimulation in IVF? AB - Among 599 trials of in-vitro fertilization (IVF) treatment, complicated ovarian hyperstimulation (OHSS) was diagnosed in 14 cases (2.5%) on the basis of heavy abdominal discomfort and echographic findings (ascites, ovarian enlargement with cysts). Among eight hospitalized patients, four presented with a haemoconcentration and/or electrolytic disturbances. OHSS cases were compared with two control groups for a series of criteria: age, aetiology of infertility, total dose of human menopausal gonadotrophin (HMG), day of oocyte collection, oestradiol (E2) peak level, rate of E2 increase, number of oocytes, number of embryos transferred and embryonic vitality scores. Comparison with a random group of normal IVF trials showed a significant difference for the following parameters: E2 peak level and rate of increase, E2/dose of HMG, E2/day of egg collection and number of oocytes. When OHSS cases were compared to another control group consisting only of high E2 responders (peak E2 greater than 2700 pg/ml), no significant difference was found for any of the above-mentioned criteria. In view of this lack of predictive power of individual criteria, stepwise discriminant analysis was applied, showing that this method might provide a predictive mathematical function for evaluating the risk of OHSS before human chorionic gonadotrophin (HCG) administration. Such a formula, however, should be validated by a multicentric study in which a greater number of OHSS cases would be tested. PMID- 1761667 TI - The history of endometriosis: identifying the disease. AB - The history of endometriosis is reviewed in the light of today's clinical and pathological knowledge of this disease. Prior to Sampson's report in 1921, attention was focused on the enclosed type of endometriosis, sited deep in the pelvis and called adenomyosis externa. Sampson's first hypothesis, that rupture of an ovarian endometrioma caused superficial peritoneal endometriosis, was probably changed after this observation that the free, superficial peritoneal implants reacted like eutopic endometrium. These implants were recognized as implants from menstrual blood regurgitated into the pelvic cavity. Adenomyosis externa, ovarian endometrioma and peritoneal endometriosis then came to be regarded as the same disease. In the light of today's knowledge, it may be important to remember this progressive understanding in the nosology of what is now universally called pelvic endometriosis. PMID- 1761668 TI - Some disturbances of acrosomal development and function in human spermatozoa. AB - Disturbances of acrosomal development and function significantly impair the fertilizing capacity of spermatozoa. Therefore, evaluation of acrosomal morphology and function is of particular importance in the diagnostic testing of male infertility. Acrosomal disturbances include either specific defects showing a complete absence of certain acrosomal structures or various acrosomal malformations in combination with nuclear or flagellar defects which indicate acquired testicular disorders. As examples of specific acrosomal defects, the syndrome of round-headed spermatozoa (globozoospermia), the crater defect syndrome and the syndrome of decapitated spermatozoa are discussed. In addition to disturbances of acrosomal morphology, the assessment of acrosomal proteinase activity and the acrosome reaction as a method of evaluating impaired acrosomal functions is discussed. Clinical examples demonstrate the importance of these sperm function tests in the fertility testing of infertile men. PMID- 1761669 TI - Use of aniline blue to assess chromatin condensation in morphologically normal spermatozoa in normal and infertile men. AB - Chromatin condensation is vital for the function of the spermatozoon as the motile carrier of the paternal genome. The degree of condensation can be shown with the aid of acidic aniline blue staining, which is able to discriminate between lysine-rich histones and arginine- and cysteine-rich protamines. Using this technique and employing the Dusseldorf classification of sperm morphology in cases of disturbance of spermatogenesis, it was demonstrated that chromatin condensation is impaired not only in malformed but also in morphologically normal spermatozoa. Among morphologically normal spermatozoa, the percentages of spermatozoa with chromatin condensation disturbances increase in patients with different patterns of sperm malformation, if compared with patients with normozoospermia. PMID- 1761670 TI - Sperm morphological assessment based on strict criteria and in-vitro fertilization outcome. AB - One-hundred-and-twenty-three in-vitro fertilization (IVF) cycles were analysed in order to clarify the influence of strictly normal morphology (SNM) of spermatozoa on IVF outcome. SNM was defined using strict criteria according to Kruger with our modifications. The IVF cycles studied were divided into three groups: %SNM less than 12% (13 cycles), 12 less than 40% (68 cycles), greater than or equal to 40% (42 cycles). The cleavage rates per oocyte were higher in the groups with 12 40% and greater than or equal to 40% of %SNM than in the group with %SNM less than 12%. The embryo transfer rate per cycle increased with increasing %SNM. The overall pregnancy rate per cycle increased with increasing %SNM (7.7% in %SNM less than 12%, 22.1% in 12-40% of %SNM, and 40.5% in %SNM greater than or equal to 40%). The ongoing pregnancy rate per cycle also increased with increasing %SNM (7.7% in %SNM less than 12%, 14.7% in 12-40% of %SNM, and 31.0% in %SNM greater than or equal to 40%). The miscarriage rate was lower in %SNM greater than or equal to 40% (23.5%) than in 12-40% of %SNM (33.3%). It was suggested that %SNM is a good predictor of IVF outcome. PMID- 1761671 TI - Protective role of superoxide dismutase in human sperm motility: superoxide dismutase activity and lipid peroxide in human seminal plasma and spermatozoa. AB - The levels of superoxide dismutase (SOD), a highly specific scavenging enzyme for superoxide anion radicals (O2-), and lipid peroxide produced by oxygen free radicals were measured in human seminal plasma and spermatozoa. Seminal plasma contained 366.8 +/- 20.9 U/ml (mean +/- SE) of SOD activity. SOD activity in human spermatozoa showed a significant correlation to the number of motile spermatozoa, while the activity in seminal plasma did not relate to the sperm concentration or motility. The lipid peroxide concentration in seminal plasma was 6.22 +/- 0.46 nmol/ml and had no significant relationship to sperm concentration or motility. The malondialdehyde (MDA) concentration in spermatozoa was significantly related to the number of immotile spermatozoa. A decrease in the motility of spermatozoa incubated in medium without seminal plasma was observed after 120 min, while the MDA concentration of the spermatozoa increased. Addition of exogenous SOD (400 U/ml) to the sperm suspension significantly decreased this loss of motility and the increase of the MDA concentration. These data suggest a significant role for SOD in sperm motility. It seems that lipid peroxidation of human spermatozoa may cause loss of motility and that SOD may inhibit this lipid peroxidation. These results suggest that SOD may have a possible clinical application in the use of spermatozoa for in-vitro fertilization (IVF) or artificial insemination. PMID- 1761672 TI - Feasibility of semen collection and cryopreservation during chemotherapy. AB - Collection and cryopreservation of semen was undertaken in a 40-year-old man undergoing combination cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy for diffuse large cell lymphoma. Semen samples worthy of cryopreservation could be obtained through 39 days of therapy, with azoospermia observed after 70 days. Although pregnancy has not been attempted in the current case, reports by others suggest that normal outcomes can be expected with thawed semen collected during chemotherapy. PMID- 1761673 TI - The use of a pretherapeutic, predictive score to determine inclusion criteria for the non-surgical treatment of ectopic pregnancy. AB - Non-surgical management of ectopic pregnancy has recently become an alternative to surgery. We have investigated a pretherapeutic score to define the indication for non-surgical and surgical treatment in 61 patients with ectopic pregnancy. The score was performed before the patients' inclusion in a nonsurgical management scheme. The score used six criteria which were evaluated on a scale from 1 to 3: gestational age, human chorionic gonadotrophin (HCG) level, progesterone level, abdominal pain, haemoperitoneum volume and haematosalpinx diameter (estimated by laparoscopy or transvaginal ultrasound). Three scores, 10, 11 and 12, were studied in order to define a threshold beyond which surgical treatment should be performed. For each one, sensitivity, specificity and positive and negative predictive values were analysed. The success rate of non surgical treatment was 75% (46/61). For patients undergoing medical treatment with a score less than or equal to 12, the success rate was significantly higher compared with a success rate of 50% when the score was greater than 12. We conclude that a score less than or equal to 12 permits non-surgical management with a success rate of 82%. A score greater than 12 indicates that laparoscopic surgery may be more suitable. The choice between different non-surgical approaches, did not influence the success rate. When ultrasound reveals embryo heart activity, medical treatment is always possible if the score is less than or equal to 12. PMID- 1761674 TI - Subsequent fertility for patients presenting with an ectopic pregnancy and having an intra-uterine device in situ. AB - Of 503 ectopic pregnancies (EP) dealt with surgically using conservative laparoscopic techniques, 153 (30.4%) occurred in patients with an intra-uterine device (IUD) in situ. Examination of the characteristics of the EP revealed that the fimbrial location was more frequent among patients with an IUD whereas a significantly higher proportion were located in the isthmus in the group of patients without an IUD. Whereas the condition of the tubal wall did not differ according to the presence or absence of an IUD, adhesions and obstructed or non existent contralateral tubes were significantly less frequent among patients with an IUD in situ. Two hundred and twenty three patients desired pregnancy, 30 of whom had an IUD in situ when the EP was diagnosed. The subsequent fertility for these 30 patients with an IUD was shown by rates for intrauterine pregnancy (IUP), recurrent EP and infertility of 96.7, 3.3 and 0% respectively. These results were significantly better than those for women who had no IUD, the figures for this group being 59, 13.4 and 27.4%, respectively. The favourable prognosis was due solely to the fact that women with an IUD had far fewer negative antecedents and that the EP probably occurred due to impaired ciliary action which is reversible when the IUD is removed. PMID- 1761675 TI - Evaluating biochemical identification systems. PMID- 1761676 TI - Antigenic properties of Borrelia burgdorferi isolated from Ixodes ovatus and Ixodes persulcatus in Hokkaido, Japan. AB - Spirochete strains HP3 and HO14, isolated from Ixodes persulcatus and I. ovatus in Hokkaido in 1989, were the first isolates of Borrelia burgdorferi, the etiological agent of Lyme disease, to be recognized in Japan. Antigenic properties of the Japanese strains were compared with those of the strains isolated in the United States (B31 and 297) and Europe (IRS, P/Gau, P/Bi, 2/B45, and 3/B56) by Western blotting (immunoblotting), by using monoclonal antibodies (MAbs) against strains B31 and P/Bi. The Japanese strains reacted with MAb U40 against the 41-kDa antigen. MAb E34a31 against Osp A reacted with all the strains tested except for strain HP3. Furthermore, MAb U31b against Osp A reacted with all the American and European strains but did not react with the Japanese strains. When MAbs against Osp B were used, MAb E34b reacted only with European strains and MAb U34b reacted only with the American strains. However, neither showed reactivity to two Japanese strains. MAb E60 against 60-kDa antigen reacted with all the U.S. and European strains and strain HP3 but did not react with Japanese strain HO14. These results indicate that the antigenicity of the Japanese strains isolated from two species of ixodid ticks is different from that of the strains isolated in the United States and Europe. It is suggested that the Japanese strains are much more suitable than the U.S. or European strains as the antigen source for the serodiagnosis of Lyme disease in Japan. PMID- 1761677 TI - Identification of genomic clonal types of Actinobacillus actinomycetemcomitans by restriction endonuclease analysis. AB - To evaluate its utility in discriminating different strains, restriction endonuclease analysis was applied to 12 strains of Actinobacillus actinomycetemcomitans (3 serotype a, 5 serotype b, and 4 serotype c strains). DNA isolated from each strain was digested by 12 different restriction endonucleases, and the electrophoretic banding patterns of the resulting DNA fragments were compared. The DNA fragment patterns produced by SalI, XhoI, and XbaI for the 12 A. actinomycetemcomitans strains were simple (less than 30 bands) and allowed us to recognize easily 10 distinct genomic clonal types. The three serotype a strains exhibited distinctly different clonal types from one another, the five serotype b strains exhibited an additional four distinct clonal types, and the four serotype c strains showed another three different clonal types. The other endonucleases tested were less useful in typing A. actinomycetemcomitans. We conclude that restriction endonuclease analysis is a powerful tool for typing and discerning genetic heterogeneity and homogeneity among A. actinomycetemcomitans strains. It should, therefore, be very useful for epidemiologic studies. PMID- 1761678 TI - Clinical and microbiological observations on CDC group DF-3, a gram-negative coccobacillus. AB - Sequential stool cultures submitted for routine culture were screened for the presence of CDC group DF-3. Of 690 specimens, 11 (1.6%) yielded moderate to heavy growth of DF-3. Information on the 11 patients from whom these specimens were obtained showed that 4 had a history of prolonged diarrheal disease that resolved after specific therapy to eradicate DF-3, while for the other 7 patients no clear role could be established. Microbiological characterization of the stool isolates and 10 CDC strains of DF-3 suggested the presence of two subtypes within the group. Antibiotic susceptibility studies showed DF-3 to be relatively resistant to a wide variety of antibiotics. PMID- 1761679 TI - Longitudinal study of the microbiology of endemic trachoma. AB - A longitudinal study of trachoma in 100 members of nine Tanzanian families was conducted to assess the sources of variation in the laboratory identification of trachoma and the changes that might occur over time. Multiple conjunctival swabs were collected every 3 months for 1 year and examined by direct fluorescent antibody cytology (DFA), enzyme immunoassay, or microimmunofluorescence serology for tear antichlamydial antibodies. DFA specimens collected 5 min apart had a discordance rate of 10% and this is attributable to sampling variation. DFA specimens collected 2 days or more apart show a 25% discordance rate. This suggests a biologic variation in shedding in addition to sampling variation. Good correlation existed between the DFA and the enzyme immunoassay. Tear serology was quite specific in predicting the presence of clinical disease and correlated with the other two antigen detection tests, although it does not seem to offer any practical advantages. These studies indicate that there is considerable variation in the shedding of chlamydia by people living in trachoma-endemic areas. PMID- 1761680 TI - Application of colorimetric microdilution plate hybridization for rapid genetic identification of 22 Mycobacterium species. AB - Quantitative microdilution plate hybridization was used to identify 22 Mycobacterium species. DNAs of clinical strains were rapidly extracted and labeled with photoreactive biotin. Labeled DNAs were distributed into wells of a microdilution plate in which reference DNAs had been immobilized. After 2 h of hybridization, hybridized DNAs were quantitatively detected with peroxidase conjugated streptavidin and the substrate, tetramethylbenzidine. This method could differentiate among 20 of the 22 Mycobacterium species tested. The type strains of Mycobacterium tuberculosis and M. bovis were genetically highly related and could not be differentiated by this method. Of 194 biochemically identified human clinical strains, 178 (90%) were genetically identified within 3 h of the small-scale DNA extraction. PMID- 1761681 TI - Comparison of the PREMIER cryptococcal antigen enzyme immunoassay and the latex agglutination assay for detection of cryptococcal antigens. AB - A new enzyme immunoassay (EIA), PREMIER Cryptococcal Antigen, was compared with latex agglutination (LA) for the detection and quantitation of circulating capsular polysaccharide antigen from Cryptococcus neoformans. The clinical evaluation of PREMIER EIA as a screening assay, including 475 specimens with 120 LA and EIA positives, resulted in 99% sensitivity and 97% specificity. The clinical specimens included sera and cerebrospinal fluids as well as 10 rheumatoid factor-positive and 20 anti-nuclear antibody-positive serum samples. This monoclonal antibody-based assay detects serotypes A to D at 0.63, 0.63, 7.8, and 62 ng/ml, respectively. With three different known positive specimens, the assay was found to yield coefficients of variation of 2 to 12% for intra- and interassay comparisons of precision and reproducibility. The primary use for semiquantitative values derived with the LA or EIA is to follow the course of disease and monitor drug therapies. The present data suggest that the PREMIER EIA will be a valuable method for this purpose. We conclude that the PREMIER Cryptococcal Antigen EIA provides a rapid, convenient, and reliable antigen detection method for screening and semiquantitative determination of antigen levels. PMID- 1761682 TI - Characterization of an immunoreactive species-specific 19-kilodalton outer membrane protein from Helicobacter pylori by using a monoclonal antibody. AB - Immunoblotting experiments on hyperimmune rabbit serum and sera from patients with Helicobacter pylori gastritis showed a consistent antibody response to a 19 kDa outer membrane protein antigen. A monoclonal antibody, designated HP 40, which reacted by Western immunoblotting with this protein was produced. It was shared by all H. pylori strains tested (D 273, NCTC 11637, and 24 wild strains) but not by the thermophilic Campylobacter species, Campylobacter fetus, Helicobacter mustellae, or Helicobacter fennelliae. Immunogold staining suggested that the 19-kDa antigen was exposed on the outer surface of the bacteria. Its functional role and effectiveness as a serological diagnostic tool are under study. PMID- 1761683 TI - Application of a monoclonal antibody-based enzyme-linked immunosorbent assay for detection of an inflammatory response antigen in subclinical mastitic milk samples. AB - A monoclonal antibody to a 23.5-kDa bovine inflammatory antigen present in high levels in mastitic milk has been used in an antigen-capture enzyme-linked immunosorbent assay (ELISA) to screen milk samples from herds of cattle for subclinical mastitis. The results from 20 herds with a total of 2,612 quarter samples are presented. Good correlation was observed between the ELISA level and the milk cell count (MCC). The results demonstrated an average of 5% false negatives (1.8% associated with isolates of Staphylococcus aureus and/or Streptococcus spp.) and 7.7% false positives for each herd in relation to mastitic (greater than 400,000 cells per ml) or nonmastitic (less than 400,000 cells per ml) MCCs. PMID- 1761684 TI - Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria. AB - Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) is a water-soluble protein released from parasitized erythrocytes into in vitro culture supernatants. This study sought to determine whether PfHRP-2 could be detected in the plasma of humans with P. falciparum malaria. A monoclonal antibody (1E1) is described that binds to PfHRP-2. By using monoclonal antibody 1E1, PfHRP-2 was identified by Western blot (immunoblot) analysis in the plasma of 37 of 39 (95%) patients experiencing either a first or repeat episodes of P. falciparum malaria and by dot blot analysis in the plasma of 40 of 41 patients tested. PfHRP-2 was not detected in 30 control, uninfected subjects. The current demonstration of PfHRP-2 in plasma, plus the fact that it is a structurally well-characterized molecule present in all natural isolates of P. falciparum tested, makes PfHRP-2 of interest for its potential effects on the host immune system and as an antigen for specific diagnosis of malaria. PMID- 1761685 TI - Serodiagnosis of Helicobacter pylori: comparison of enzyme-linked immunosorbent assays. AB - Enzyme-linked immunosorbent assays (ELISAs) have been developed to diagnose Helicobacter pylori infection. However, the methods are not standardized. We therefore prospectively evaluated the sensitivities and specificities of ELISAs developed in the United States and the United Kingdom in a study population comprising 41 consecutive symptomatic outpatients and 35 volunteers. At endoscopy, multiple biopsies were obtained for histology and culture and stained sections were graded for chronic gastritis, active chronic gastritis, and density of H. pylori. Serum samples were analyzed for H. pylori by ELISA. The first set of assays for immunoglobulin G (IgG) and IgA used a pool of sonicated isolates of H. pylori from five patients in the United States (antigen A). The second set of assays, developed in the United Kingdom, used three different antigens: antigen 1, an acid-extractable surface antigen; antigen 2, an acid-extractable antigen from an aflagellate variant; and antigen 3, a urease-containing fraction. Cutoff scores for positive results were determined a priori on the basis of previous serological studies. There was close agreement between histology and culture. In the study population, 36% of the individuals were H. pylori positive. The diagnostic value of the different ELISAs were highly comparable, and the crude antigens performed as well as the more purified antigens. The antigen A IgG had a sensitivity and specificity of 96 and 94%, respectively; the values for antigen 1 were 93 and 96%, respectively. The antigen A IgA and antigen 3 assays were the least sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761686 TI - Fluorescence immunoassay for detecting periodontal bacterial pathogens in plaque. AB - A particle concentration fluorescence immunoassay has been modified into a bacterial concentration fluorescence immunoassay (BCFIA) to rapidly detect periodontopathic bacteria in human plaque samples. The BCFIA utilizes fluorescently tagged monoclonal antibodies (MAbs) directed against the lipopolysaccharide of selected gram-negative plaque bacteria. Microorganisms closely associated with periodontal disease that can be identified in plaque with the BCFIA include Porphyromonas gingivalis, Bacteroides intermedius, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Eikenella corrodens. Briefly, the procedure involved mixing a patient's plaque sample or other bacterial preparation with a species-specific fluorescein isothiocyanate labeled MAb in a specialized microtiter plate. This mixture was incubated to allow binding of the MAb to its homologous bacteria. The bound and unbound fluorescent tagged MAbs were separated by filtration in the modified microtiter plate, and the total bacterial bound fluorescence was determined with a fluorimeter. The number of a specific bacterial species in a given plaque sample or other bacterial suspension was estimated by reference to a primary standard carried through the BCFIA. The lower detection limit of the BCFIA was 10(3) to 10(4) bacterial cells from single cultures of bacteria or 10(4) bacterial cells in mixed cultures. The coefficient of variation within and between plates for each of the five bacterium-specific MAbs in screening plaque for the periodontal pathogens was less than 10%. These results demonstrate that microbes in plaque can be used as the solid phase in the BCFIA to detect and quantitate MAbs associated with specific bacteria quickly and reliably. PMID- 1761687 TI - Mycobacterium paratuberculosis antigen D: characterization and evidence that it is a bacterioferritin. AB - By using a combination of agarose and polyacrylamide gel electrophoresis, Mycobacterium paratuberculosis antigen D was resolved from a crude sonicated preparation of the organism and characterized as a component with a molecular mass of approximately 400,000 Da. While this component was composed mainly of protein, with unusually high proportions of glutamic acid and leucine, it was resistant to digestion with a number of proteolytic enzymes. Structural detail revealed by electron microscopy, amino acid sequence data, and the demonstration of a Soret band in its absorption spectrum indicated that antigen D was similar to an Escherichia coli bacterioferritin. PMID- 1761688 TI - Chromatographic purification and characterization of antigens A and D from Mycobacterium paratuberculosis and their use in enzyme-linked immunosorbent assays for diagnosis of paratuberculosis in sheep. AB - The protein antigens A and D were purified from culture filtrates and sonic extracts of laboratory strains of Mycobacterium paratuberculosis by salt precipitation and chromatography. The characterization of antigen A is shown here, and both antigens were evaluated along with lipoarabinomannan antigen in indirect enzyme-linked immunosorbent assays (ELISA) for the serodiagnosis of ovine paratuberculosis. After anion-exchange (DEAE-5PW) and hydrophobic (phenyl 5PW) chromatography using high-performance liquid chromatography, antigen A showed a prominant band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at 31 kDa with small amounts of low-molecular-mass proteins but with no evidence of antigen D. A single precipitin arc was evident with purified antigen A in crossed immunoelectrophoresis. The determination of the N-terminal amino acid sequence showed a high degree of homology between the 31-kDa component of antigen A and antigens of the BCG85 complex of Mycobacterium bovis BCG, a total of 24 of 26 residues being identical to those of BCG85C. A prominant SDS-PAGE band at 400 kDa and a single crossed-immunoelectrophoresis arc was also evident for antigen D after gel filtration (Sephacryl S-200), anion exchange (DEAE-Sephacel), and concanavalin A-Sepharose affinity chromatography. By ELISA, purified antigen A detected antibody in the sera of 18 of 22 paratuberculosis-infected sheep (82% sensitivity), whereas the purified antigen D detected antibody in all 22 infected animals (100% sensitivity). Combined ELISA results showed increased specificity with some loss in sensitivity. PMID- 1761689 TI - Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens. AB - Clearances of mannan antigen from Candida albicans and glucuronoxylomannan antigen from Cryptococcus neoformans were examined in nonimmune rabbits by using self-prepared latex agglutination tests. Injected intravenously, 20 mg of Candida mannan antigen was cleared from the serum with a half-life of approximately 2 h. In contrast, 20 micrograms of Cryptococcus glucuronoxylomannan antigen had a half life in serum of approximately 24 h. At the latest, 9 h after injection, both antigens were no longer detectable without pretreatment of serum samples with protease and heating to 100 degrees C, thus indicating rapid binding by serum proteins other than immunoglobulins. Candida mannan antigen clearance was also examined in nonimmune mice after intravenous injection of (i) 200 micrograms of Candida mannan antigen, which accumulated in the liver and spleen and persisted for 97 days; (ii) 2 x 10(7) ethanol-killed Candida blastospores, which was accompanied by rapid clearance of mannan from the blood but accumulation of mannan in the liver and spleen and slow clearance from these organs; (iii) 6 x 10(6) viable C. albicans cells (lethal infection), which resulted in a rapid decrease of Candida CFU in the blood, liver, and spleen during the first 8 h, after which blood cultures were negative on day 2 and viable Candida burdens in the liver and spleen persisted at 10(5) CFU/g, whereas Candida mannan antigen continued to circulate in the bloodstream and accumulated in the liver and spleen. PMID- 1761690 TI - Identification of Vibrio vulnificus O serovars with antilipopolysaccharide monoclonal antibody. AB - A serotyping scheme for Vibrio vulnificus predicated on the detection of lipopolysaccharide (LPS) antigens is proposed. The serovar O typing scheme used to type V. vulnificus employs polyclonal antisera raised in rabbits immunized with heat-killed whole-cell vaccines. Polyclonal typing sera produced in this manner cross-react with heterologous strains. Affinity purification of polyclonal antisera with LPS affinity columns resolved some of these cross-reactions; however, affinity-purified polyclonal antisera still showed cross-reactions that were nonreciprocal. On the basis of the serological patterns that were obtained with affinity-purified polyclonal antisera, V. vulnificus strains were selected as vaccine strains for production of monoclonal antibody. Spleen cells harvested from BALB/c mice immunized with formalin-killed V. vulnificus cells were fused with SP2/O-Ag 14 myeloma cells. Hybridomas were screened by using LPS and whole cell enzyme-linked immunosorbent assay to identify clones secreting LPS-specific antibodies. Monoclonal antibodies identified five LPS serological varieties of V. vulnificus and a single serovar each for Vibrio damsela and Vibrio hollisae. No cross-reactions between V. vulnificus and V. hollisae or V. damsela were observed. PMID- 1761692 TI - Genetic dissimilarity of commensal strains of Candida spp. carried in different anatomical locations of the same healthy women. AB - Candida spp. carriage and strain relatedness were assessed in 52 healthy women at 17 anatomical locations by using an isolation procedure which assesses carriage intensity and by using a computer-assisted DNA fingerprinting system which computes genetic similarity between strains on the basis of the patterns of Southern blots probed with the moderately repetitive sequence Ca3. Candida spp. were cultured from 73% of the test individuals, most frequently from the oral (56%), vulvovaginal (40%), and anorectal (24%) regions. Half of the test individuals with Candida spp. carried the organism simultaneously in more than one of the three general areas of carriage. Isolates from different body locations of the same individual were either completely unrelated, identical, or highly similar but nonidentical. In 11 cases in which Candida spp. were simultaneously isolated from the oral cavity and vaginal canal, seven pairs of isolates were genetically unrelated and four pairs were similar but nonidentical. In the latter cases, the isolate pairs each appear to have arisen by genetic divergence from a single progenitor. A comparison of the genetic relatedness of isolates from different individuals further uncovered a single strain which was vaginospecific in the Iowa City, Iowa area and reduced genetic diversity among vulvovaginal strains compared with those isolated from other body locations. These results suggest that strains adapt to different anatomical locations and, conversely, that in a healthy individual there is anatomical selection of vaginotropic, anotropic and orotropic strains of Candida spp. PMID- 1761691 TI - Murine intestinal antibody response to heterologous rotavirus infection. AB - Rotavirus is the most important worldwide cause of severe gastroenteritis. Extensive efforts have been devoted to the design of a vaccine that will prevent disease, but development of a more effective vaccine strategy may require progress in the understanding of the mucosal immune response to replicating viral antigens. In this article, we report the characterization of the intestinal antibody response of a murine model to heterologous infection with the rhesus rotavirus vaccine strain. We have adapted the enzyme-linked immunospot assay to measure this response without the difficulties associated with measurement of antibodies in intestinal contents or the artifacts associated with culturing of lymphocytes. The predominant response in terms of antibody-secreting cells (ASC) is seen in the small intestine lamina propria, which can be measured within 4 days of infection, peaks 3 weeks after infection, and remains near that level for longer than 8 weeks. The magnitude of the immunoglobulin A (IgA) cell response is approximately 10 times greater than the intestinal IgG cell response, and IgM cells are rare. Virus-specific ASC constitute approximately 50% of all ASC in the gut at the peak of the virus-specific response. This response is considerably greater than responses to nonreplicating mucosal antigens measured by similar techniques. Enteral infection engenders minimal virus-specific ASC response in the spleen. Rhesus rotavirus-specific enzyme-linked immunosorbent assay and neutralization assays of serum and intestinal contents did not correlate with virus-specific ASC response. PMID- 1761694 TI - Collaborative feasibility study of a biphasic system (Roche Septi-Chek AFB) for rapid detection and isolation of mycobacteria. AB - A study to delineate the feasibility of a biphasic-culture approach for detection and isolation of mycobacteria from clinical specimens except blood was conducted in four medical centers. The biphasic system (Septi-Chek AFB, Roche Diagnostic Systems, Nutley, N.J.) was compared with conventional mycobacterial isolation media and the BACTEC system. Septi-Chek AFB showed the highest degree of mycobacterial recovery. In addition, Septi-Chek AFB consistently shortened the time required for recovery of mycobacteria from clinical specimens and supported the growth of small inoculum numbers of stock cultures of 14 mycobacterial species. The study indicates the feasibility and potential advantages of the biphasic approach for detection and isolation of mycobacteria. PMID- 1761693 TI - Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid. AB - The diagnosis of congenital syphilis continues to pose a difficult clinical challenge. Because the serodiagnosis of congenital syphilis has significant limitations, the direct detection of Treponema pallidum in suspect neonatal tissues or body fluids represents a desirable alternate diagnostic strategy. We developed and applied the polymerase chain reaction (PCR) for the detection of T. pallidum in clinical material relevant to the diagnosis of congenital syphilis but which typically contain factors inhibitory for the PCR. Four methods of specimen processing were examined to circumvent PCR inhibition; clinical materials included amniotic fluids, neonatal sera, and neonatal cerebrospinal fluids. The PCR was 100% specific for T. T. pallidum compared with the sensitive rabbit infectivity test (RIT) for all clinical materials tested. For amniotic fluids, the PCR was 100% sensitive when correlated with the RIT but had a lesser sensitivity when applied to sera or cerebrospinal fluids, which typically contain few treponemes. The combined sensitivity of the PCR for all clinical samples was 78%. Positive PCR results also were obtained among some clinical specimens for which RIT was not performed; these results correlated well with either stigmata or risk factors for congenital syphilis. The combined results suggest that the PCR can be a useful adjunct to the diagnosis and clinical management of congenital syphilis and that it will provide a valuable tool for investigations of the pathogenesis of the disorder. PMID- 1761695 TI - Variability in commercial histoplasma complement fixation antigens. AB - Using Immuno-Mycologics (IMMY; Norman, Okla.) histoplasmal yeast (HY) and mycelial (HM) antibody complement fixation test antigens, we retested 1,386 samples that were initially tested with Meridian Diagnostics, Inc. (Cincinnati, Ohio), antigens. Histoplasma antibody was identified (greater than or equal to 1:16) in 20% of HY and 5% of HM samples reported to have titers of less than 1:8 with Meridian reagents. IMMY titers were at least fourfold higher than Meridian titers in 39% of HY and 54% of HM samples that initially had titers of greater than or equal to 1:8 with Meridian antigens. Because 30 of 58 (52%) samples from confirmed cases of histoplasmosis yielded negative results with Meridian antigens and positive results upon retesting with IMMY antigens, we concluded that the Meridian antigens had less reactivity with human histoplasmal antibody. PMID- 1761696 TI - Use of pooled formalin-preserved fecal specimens to detect Giardia lamblia. AB - Three formalin-preserved fecal specimens from the same child attending a child care center were pooled and compared with the three separate individual specimens by a single microscopic examination of concentration sediment for Giardia lamblia. The sensitivity of the pooled system was 100% when two or more individual specimens were positive and 88% when only one individual specimen was positive. The organism density in a single specimen was not a factor of whether the pool of specimens was positive or negative. Nearly half of the pools that contained positive specimens had only one of three specimens with positive results, reinforcing the need for multiple stool examinations when diagnosing G. lamblia infections. PMID- 1761697 TI - Evaluation of the An-Ident system and an indole spot test for the rapid differentiation of porcine treponemes. AB - The An-Ident strip system (Analytab Products Inc., St-Laurent, Quebec, Canada) was evaluated for its ability to differentiate Treponema hyodysenteriae from Treponema innocens. Of the 20 tests included on this strip, 15 yielded identical results for the two species. Among the other five assays, none could be considered as a positive discriminator for the two species. However, when an indole spot test with 1% p-dimethylaminocinnamaldehyde was used in parallel, all reference strains and 97% of the isolates of T. hyodysenteriae were positive, whereas all isolates of T. innocens were negative. Our results indicate that An Indent is of little value for the differentiation of the two species. Our results also suggest that a rapid and simple differentiation between T. hyodysenteriae and T. innocens can be achieved by using the hemolysis and ring phenomenon tests in conjunction with an indole spot test. PMID- 1761698 TI - Isolation and characterization of Borrelia burgdorferi from Illinois Ixodes dammini. AB - Ixodes dammini ticks from two northwestern Illinois sites were found to be infected with Borrelia burgdorferi at rates of 19 and 32%. B. burgdorferi isolates, one from each site, had protein and antigenic patterns similar to those of the B-31 strain. An indirect immunofluorescence method proved to be more sensitive than dark-field microscopy in detection of these spirochetes. A modified BSK medium containing rifampin was found to be more efficient for spirochete isolation than unsupplemented BSK medium. PMID- 1761699 TI - Detection of untreated mycobacteria by using polymerase chain reaction and specific DNA probes. AB - A method for specific identification of mycobacteria by using the polymerase chain reaction on organisms taken from liquid cultures, frozen suspensions, or colonies grown on Lowenstein-Jensen slants is presented. This direct detection of mycobacterial organisms has important implications for strain typing and diagnosis. PMID- 1761700 TI - Indirect immunofluorescence assay for detection of Helicobacter pylori in human gastric mucosal biopsies. AB - To determine sensitivity and specificity of immunofluorescence assay (IFA) for detection of Helicobacter pylori, we studied 151 patients. Biopsies of gastric mucosae were obtained for culture, histological testing, and IFA. H. pylori serum antibodies were tested by enzyme-linked immunosorbent assay. IFA was done on Formalin-preserved, paraffin-embedded biopsies by using rabbit anti-H. pylori and goat anti-rabbit gamma globulin-fluorescein isothiocyanate conjugate. The sensitivity and specificity of IFA compared with culture and Warthin-Starry stain were 93 and 95%, respectively. IFA is an accurate method for the diagnosis of H. pylori infection. PMID- 1761701 TI - Detection of rubella-specific immunoglobulin G: comparison of the enzyme-linked immunosorbent assay and an automated microparticle enzyme immunoassay (IMx). AB - An automated microparticle enzyme immunoassay (IMx Rubella IgG Antibody Assay; Abbott Laboratories, North Chicago, Ill.) was compared with a conventional enzyme linked immunosorbent assay (ELISA) for detection of rubella-specific immunoglobulin G (IgG) in 400 consecutive antenatal patients. There was complete agreement between the two tests in this population, which had a positivity rate of 99% for rubella-specific IgG antibodies. The performance of the IMx was also evaluated at the cutoff zone by assaying 64 selected antenatal serum samples with low or negative rubella antibody titers as determined by ELISA. Overall, the IMx was found to be a specific, sensitive assay for the detection of rubella-specific IgG and is virtually fully automated for easy performance. PMID- 1761702 TI - Isolation of Mycobacterium shimoidei from a patient with cavitary pulmonary disease. AB - Mycobacterium shimoidei was isolated from the sputum of a man hospitalized for cavitary pulmonary disease. This is the fourth isolation of M. shimoidei to be reported; the organism has also been isolated in Japan, Australia, and Germany. PMID- 1761703 TI - History and evolution of methods for solving the inverse problem. AB - This article serves as an introduction to the other articles in this issue devoted to the problem of the localization of neural generators. Elements of the theory of electric volume conduction are briefly introduced, as far as these apply to the interpretation of observed scalp potentials. First, some basic methods for display of the different aspects of the spatiotemporal information are described. Next, the most prominent source and volume conductor models that have been postulated for the involved forward problem are summarized. The problems of source identification and source localization, known as the inverse problem, are then formulated in terms of a parameter estimation procedure. The importance of introducing a priori information in the inverse problem, aimed at stabilizing (regularizing) the obtained solution, is emphasized. Methods for imposing such constraints are briefly outlined. PMID- 1761704 TI - Models of the human brain and the surrounding media: their influence on the reliability of source localization. AB - This article is a review of the evolution of models of the head as used in dipole source localization. Models fall into two classes: those that can be expressed in simple analytic form, such as the homogeneous sphere or spherical three-shell models, or those that can only be solved by numerical methods, such as the finite element approach. The latter models always involve heavy procedural and computational burdens. The trend over the last decade has been to use these more advanced models to estimate the error that would be incurred if one of the simpler spherical models were used instead for dipole source localization. An estimate is presented of the magnitudes of the random and systematic errors of localization that may be expected when using these methods. PMID- 1761705 TI - Principles for transformation of scalp EEG from potential field into source distribution. AB - Tracings representing simultaneously recorded values of EEG potentials from different positions on the scalp surface describe how the instantaneous potential field over the scalp surface changes with time. Each instantaneous distribution of potential can be seen as resulting from spatial integration of primary components into the potential field. These components may be derived by means of the reverse procedure: subjecting the data from the potential field to spatial differentiation as provided by the Laplacian source operator. The result is a "deblurred," i.e., a more differentiated, distribution of source components hypothetically associated with the generators of the potential field. The Laplacian source operator can be implemented as a linear combination of the instantaneous potential values, either by means of very simple electronic circuitry or in a computer. The linear combination is a standard operation in matrix algebra and is widely applied in signal processing. The formalism of matrix algebra simplifies a precise evaluation of the method in relation to conventional derivation techniques and provides further methods for analysis of the EEG data. PMID- 1761706 TI - The spline-Laplacian in clinical neurophysiology: a method to improve EEG spatial resolution. AB - An important goal of EEG research is to obtain practical methods to improve the spatial resolution of scalp-recorded potentials, i.e., to make surface data more accurately represent local underlying brain sources. This goal may be somewhat different from that of "localizing brain activity with EEG," since the latter approach often involves prior assumptions about the nature of sources. In this paper, we demonstrate that spline-Laplacian, a relatively new approach that can yield dramatic improvement in spatial resolution when average electrode spacing is less than about 3 cm. This approach is mostly independent of assumptions about sources and models of the head. The demonstration involves computer simulations, evoked potentials, normal spontaneous EEG, and epileptic spikes. PMID- 1761707 TI - Localization of seizure foci: pitfalls and caveats. AB - The pitfalls and difficulties in accurately localizing seizure foci are reviewed. Basic issues regarding modeling, volume conduction, inhomogeneities, and corticocortical propagation are discussed, and the limitations of scalp and intracranial recordings are outlined. The ambiguities in interpreting patterns and their significance are highlighted with a concluding commentary on pitfalls in defining the epileptogenic region. PMID- 1761708 TI - Expanded head surface EEG electrode array: an application to display the voltage topography of focal epileptiform discharges of mesiotemporal origin. AB - Aided by computerized voltage topographic display, conventional time-series EEG display methods were expanded. Representations of both negative and positive ends of an equivalent current dipole can be localized in EEG sampled over the head surface. Intuitive EEG analysis can be applied to source localization in three dimensions of scalp focal epileptiform discharges. PMID- 1761709 TI - Technology and equipment review. EEG storage methods. PMID- 1761710 TI - Changes in total body water during spaceflight. AB - This experiment represents the first time that it has been possible to measure a body fluid compartment by direct means during spaceflight. Based on the results observed in the five crewmen in this study, it is concluded that TBW decreases by 3.4% after 1 to 3 days of exposure to microgravity in the Space Shuttle. Some individuals appear to undergo this decrease within 24 hours. This effect may be enhanced by decreased water intake due to nausea associated with SMS. PMID- 1761711 TI - Cardiovascular adaptation to spaceflight. PMID- 1761712 TI - Echocardiographic evaluation of the cardiovascular effects of short-duration spaceflight. PMID- 1761713 TI - Space medicine: answering the challenge. PMID- 1761714 TI - Cerebral blood flow: comparison of ground-based and spaceflight data and correlation with space adaptation syndrome. PMID- 1761715 TI - Blood and urine responses to ingesting fluids of various salt and glucose concentrations. AB - Several hours before returning to Earth, Space Shuttle astronauts consume fluid and salt tablets equivalent to a liter of 0.9% saline as a countermeasure to postflight orthostatic intolerance. This countermeasure is not completely successful. Therefore, in search of a countermeasure that would protect against orthostatic intolerance better and for a longer duration, the authors compared the blood and urine responses of five men (21-41 yr) after they drank 1 L of 0.9% saline to their responses after drinking five other solutions: distilled water, 1% glucose, 0.74% saline with 1% glucose, 0.9% saline with 1% glucose, and 1.07% saline. Each subject ingested a different solution on 6 different days and remained seated for the ensuing 4 hours. Heart rate, blood pressures, and urine variables were measured before ingestion of the fluids and every 30 minutes thereafter; blood samples were drawn before, immediately after, and every 60 minutes after ingestion. Change in plasma volume, which was estimated from hemoglobin and hematocrit, was considered the most critical variable. Data for all solutions were compared by analysis of variance. Since plasma volume was increased most after ingestion of 1.07% saline, all variables (at 2 hours, at 3 hours and at 4 hours) were compared between 1.07% saline and 0.9% saline, the current countermeasure. Plasma volume was increased more after 1.07% saline than after 0.9% saline, and this difference was most significant at 4 hours after ingestion (P = .056). Diuresis occurred promptly after ingestion of the two saline-free solutions, water and 1% glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761716 TI - Development of lower body negative pressure as a countermeasure for orthostatic intolerance. AB - Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed towards increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP. PMID- 1761717 TI - Orthostatic function during a stand test before and after head-up or head-down bedrest. AB - Astronauts may exhibit orthostatic dysfunction upon returning to 1 g after space flight. Understanding cardiovascular changes at 0 G will provide insights into the mechanisms of the loss of orthostatic tolerance, whether due to space flight or bedrest. Bedrest is one model used to produce cardiovascular changes that are associated with space flight. In the current study, young male adults were placed at -5 degrees, +10, +20, or +42 degrees bedrest (0, 1/6, 1/3, and 2/3g, respectively) for 6 hours on 4 different days. This was preceded and followed by a stand test: 5 minutes in the supine position, and then 5 minutes in the standing position, with the feet 9 inches apart and 6 inches from the wall. Cardiovascular values were measured at 1-minute intervals. Systolic and diastolic pressures were measured using an automated blood pressure device; mean arterial pressure (MAP; mm Hg) was calculated. Heart rate (bpm) and cardiac parameters were measured with a thoracic impedance device. Minute 3, 4, and 5 values were used to determine whether there were time or angle effects. Of six subjects, one reported nausea upon 3 minutes of standing after 6 hours of bedrest at -5 degrees. The same subject was lightheaded in the first minute of standing after 6 hours of bedrest at +10 degrees. Mean heart rate pre-bedrest in the supine position was 63 and increased by 24 bpm on standing. Heart rate post-bedrest in the supine position was 65 and increased by 35 bpm on standing; standing heart rate increased 11 bpm after -5 degrees bedrest. The increases after +10 degrees, +20 degrees, and +42 degrees tilts were 4, 3, and 4 bpm, respectively. Changes in the mean arterial blood pressure were minimal. Results from the stand test pre- and post- 6 hours of bedrest at -5 degrees but not at +10 degrees, +20 degrees, or +42 degrees are similar to those after space flight. PMID- 1761718 TI - Human vestibular function and weightlessness. AB - This article presents the concept of a spatial orientation/motion perceptual system, the contributions of the vestibular receptors to this system, and apparatus and training procedures and observations to allow astronauts to preadapt to weightlessness. The author also discusses perceptual reactions to prolonged weightlessness. PMID- 1761719 TI - Cerebral blood flow during +Gz acceleration as measured by transcranial Doppler. PMID- 1761720 TI - Cerebral blood flow velocities by transcranial Doppler during parabolic flight. AB - Microgravity is produced for 20 to 30 seconds in NASA's KC-135 aircraft at the end of a 2 G pullup for each of 40 parabolas per flight. Continuous transcranial Doppler ultrasound, arterial blood pressure, and acceleration levels were recorded for 12 male and 8 female healthy subjects without known cardiovascular or cerebrovascular disease. Recordings were made throughout 10 parabolas per subject in each of the supine, sitting, and standing postures. The data were digitized for off-line analysis using Fast Fourier Transform and other signal processing methods. A phase lag in changes to transcranial Doppler waveforms from the onset of acceleration was more pronounced in the standing position than in the sitting position. There was less of a phase lag in the supine position. These ultrasound changes preceded the more delayed variations in arterial blood pressure. The KC-135 provides a unique short-term environment that allows measurement of the human response to variations in acceleration but limits physiological monitoring of responses to a steady state of microgravity. PMID- 1761721 TI - First intramuscular administration in the U.S. Space Program. PMID- 1761722 TI - Metabolic changes observed in astronauts. AB - Study of metabolic alterations that occur during space flight can provide insight into mechanisms of physiologic regulation. Results of medical experiments with astronauts reveal rapid loss of volume (2 L) from the legs and a transient early increase in left ventricular volume index. These findings indicate that, during space flight, fluid is redistributed from the legs toward the head. In about 2 days, total body water decreases 2 to 3%. Increased levels of plasma renin activity and antidiuretic hormone while blood sodium and plasma volume are reduced suggest that space flight-associated factors are influencing the regulatory systems. In addition to fluid and electrolyte loss. Skylab astronauts lost an estimated 0.3 kg of protein. Endocrine factors, including increased cortisol and thyroxine and decreased insulin, are favorable for protein catabolism. The body appears to adapt to weightlessness at some physiologic cost. Readaptation to Earth's gravity at landing becomes another physiologic challenge. PMID- 1761723 TI - A biomedical trip to the moon and beyond. PMID- 1761724 TI - Pharmacologic considerations for Shuttle astronauts. AB - Medication usage by crewmembers in the preflight and inflight mission periods is common in the Shuttle Program. The most common medical reports for which medication is used are: space motion sickness (SMS), sleeplessness, headache, and backache. A number of medications are available in the Shuttle Medical Kit to treat these problems. Currently, astronauts test all frequently used medications before mission assignment to identify potential side-effects, problems related to performance, personal likes/dislikes, and individual therapeutic effect. However, microgravity-induced changes in drug pharmacokinetics, in combination with multiple operational factors, may significantly alter crew-member responses inflight. This article discusses those factors that may impact pharmacologic efficacy during Shuttle missions. PMID- 1761725 TI - Intraocular pressure in microgravity. PMID- 1761726 TI - Human autonomic responses to actual and simulated weightlessness. AB - Orthostatic dysfunction occurs after exposure to microgravity, and is not completely understood. The authors developed a device for stimulating carotid baroreceptors to test the hypothesis that exposure to microgravity leads to impairment of arterial baroreflex mechanisms. Data obtained before and after two head-down bedrest studies and before and after brief Space Shuttle missions indicate that baroreceptor-cardiac reflex control is impaired by simulated or actual weightlessness. The authors speculate that arterial baroreflex derangements combine with blood volume reductions and increased venous compliance to provoke orthostatic hypotension after microgravity exposure. Altered baroreflex function after missions may result from autonomic neuronal plasticity that develops during missions secondary to changes of cardiopulmonary and arterial dimensions and consequent changes of autonomic sensory input profiles. PMID- 1761727 TI - Pharmacodynamic aspects of spaceflight. AB - Little is known at present about the effects of human exposure to microgravity on the pharmacodynamics of medicinal agents. Considering the known physiologic perturbations associated with spaceflight and the effects of some of these perturbations on the pharmacodynamics of certain medicinals that act on the central nervous system, it is likely that the pharmacodynamics of at least some of these agents will be altered in individuals who are subjected to microgravity and other conditions of spaceflight. It is timely to initiate formal studies, initially in ground-based animal models and human volunteers during prolonged, head-down bed rest and eventually in animals and human volunteers exposed to microgravity, of pharmacodynamics and pharmacokinetics during spaceflight. PMID- 1761728 TI - Optimal sampling theory and population modelling: application to determination of the influence of the microgravity environment on drug distribution and elimination. AB - Newer mathematical techniques such as optimal sampling theory and NON-linear Mixed Effects Modelling (NONMEM) allow the determination of pharmacokinetics and pharmacodynamics in populations of individuals previously believed to be "too ill" or "too difficult to study." Optimal sampling determines the most information-rich times to sample the system, allowing robust parameter estimates to be determined from the minimal number of samples. NONMEM, by taking the population as the unit of analysis, allows even fragmentary patient data sets to contribute to population parameter estimates. Obviously, the microgravity environment presents extreme logistical difficulties to the performance of traditional pharmacokinetic and pharmacodynamic studies. Examples of the validation of these techniques are presented, which indicates their likely utility in the important task of determining the influence of the microgravity environment on drug distribution and elimination, even accounting for the limitations of support which will be faced in this circumstance. PMID- 1761729 TI - Effects of gravity on gastric emptying, intestinal transit, and drug absorption. AB - The effects of microgravity on the physiologic response of the human body, the physical properties of gastrointestinal contents, and the influence these responses have on drug absorption are becoming more and more critical as the duration of humans in the hostile space environment dramatically increases. In this environment, some conventional oral dosage forms may be severely limited as an effective drug regimen. To understand the effects of microgravity, one must first understand the basic forces acting on a particle moving through a walled tube such as the small intestine: gravity (FG), buoyancy (FB), and drag (FD). These forces can be combined and rearranged into a dimensionless ratio of gravitational forces to viscous forces. This is the most important dimensionless group influencing the motion of a particle relative to the fluid. Gastric emptying is highly influenced by several factors: volume, calories, exercise, size, density, temperature, viscosity, osmolality as well as those factors associated with physiologic responses: splanchnic blood flow, body position, and electrolyte balance. This array of factors can lead to variability in drug plasma levels. In the absence of gravity, the factors of size and density would appear to be most directly altered due to their dependence on the force of gravity. Intestinal transit rate in a gravity environment is highly dependent on the motility state of the GI tract either fasted or fed partly due to the higher viscosities of chyme in the fed state. In space, the absence of gravity may tend to increase the transit rate along the small intestine by decreasing the dimensionless ratio of gravitational forces to viscous forces. In zero gravity, therefore, these alterations in GI emptying and intestinal transit rate could lead to erratic plasma levels and inefficient absorption. PMID- 1761730 TI - Drug effects on orthostatic intolerance induced by bedrest. AB - Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6 degrees head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. D (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16% and caused sodium retention. Four of the 7 subjects stood for 1 hour post bedrest and HR, plasma NE and PRA responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate. The existing literature on pharmacologic countermeasures for post-flight and post-bedrest orthostatic hypotension is reviewed, and the results are discussed in that context. PMID- 1761731 TI - Protein crystal growth in microgravity. AB - Protein crystallography is a powerful method for determining the three dimensional structures of biological macromolecules. Although new methods, such as two-dimensional NMR, have demonstrated promise for determining the structures of small proteins and nucleic acids, the complete atomic arrangements within large proteins can only be determined at present using crystallographic techniques. Such crystallographic studies have been of major importance for establishing structure/function relationships that are fundamental to understanding how enzymes, nucleic acids, and other macromolecules function in biological systems. More recently, crystallographic studies of proteins have become of considerable practical interest within the pharmaceutical and biotechnology industries, as promising tools in drug design and in protein engineering. PMID- 1761732 TI - Pharmaceutical R & D in space: an industry perspective. PMID- 1761733 TI - Acute hemodynamic responses to weightlessness during parabolic flight. AB - Pilots and astronauts experience fluid shifts in variable gravity. Acute effects of fluid shifts on the cardiovascular system were monitored on NASA's KC-135 aircraft during parabolic flight. The variability of R-R intervals in the electrocardiogram was measured as an indication of vagal cardiac neural activity. R-R intervals were measured during the gravity transition from 2-G to 0-G produced by parabolic flight to assess the involvement of the autonomic nervous system in regulating the acute effects of fluid shifts. In seven subjects, a BoMed noninvasive continuous cardiac output monitor (NCCOM 3) monitored thoracic fluid index (TFI, ohms), heart rate (bpm), and cardiac output (1/min). Data were stored on a lap-top computer with the subject in one of four postures: sitting, standing, supine, and semi-supine, during one of four sets of eight to ten parabolas. Five seconds of data were averaged: before parabola onset (1.3-G); parabola entry (1.9-G); 0-G; and parabola exit (1.7-G). Three to eight parabolas were averaged for subjects in each posture; the mean for each posture was calculated. In each of five additional subjects, the coefficient of variation was calculated by dividing mean value by the standard deviation of 3 to 15 R-R intervals. Eight to ten parabolas were averaged for each postural set. Compared with values collected before 0-G, standing values during 0-G showed that the thoracic fluid index decreased 2.5 ohms, heart rate decreased 22 bpm, and cardiac output increased 1 L/min. During sitting, thoracic fluid index decreased 1.25 ohms, heart rate decreased 10 bpm, whereas cardiac output increased 0.5 L/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761734 TI - The drug development conundrum. PMID- 1761735 TI - Regurgitant valvular disease. PMID- 1761736 TI - The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione. AB - The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem. PMID- 1761737 TI - Pharmacokinetic and tolerance studies of cefpodoxime after single- and multiple dose oral administration of cefpodoxime proxetil. AB - Cefpodoxime proxetil, a third generation, broad-spectrum, oral cephalosporin, was administered in single doses of 100, 200, 400, 600, and 800 mg (dose expressed as cefpodoxime equivalents) and multiple doses of 100, 200, and 400 mg twice daily to healthy volunteers. The pharmacokinetics of the active metabolite, cefpodoxime, and tolerance of cefpodoxime proxetil were determined. Results from the single-dose study indicate that cefpodoxime exhibits nonlinear pharmacokinetics over the dose range of 100 to 800 mg. This nonlinearity is primarily due to differences in dose-normalized AUC and Cmax, urinary recovery, and half-life between one or more of the higher-dose treatment groups and the 100 mg dosing group. After multiple-dose (twice daily) administration for 15 days, steady state is achieved on the second day of dosing, and there is no drug accumulation. Cefpodoxime pharmacokinetics are linear with dose over the clinically relevant dosing range of 100 to 400 mg. Microbiologic and HPLC plasma assay results are highly correlated, with close agreement between HPLC- and microbiologic-determined pharmacokinetic parameter estimates. Cefpodoxime proxetil was well tolerated in both studies. The most frequent medical events were related to gastrointestinal problems and consisted of transient loose stools in three subjects in the single-dose study and antibiotic-associated diarrhea in one subject in the multiple-dose study. PMID- 1761738 TI - Morphology and somatotopic organisation of the central projections of afferents from tactile hairs on the hind leg of the locust. AB - The morphology and organisation of the central projections of tactile hair afferents from the hind leg of the locust, Schistocerca gregaria, were examined by staining individual hair afferents. Each tactile hair on the femur, tibia, and tarsus is innervated by a single sensory afferent, which projects to the ipsilateral half of the metathoracic ganglion. Afferents arborize in the ventralmost and lateral ventral association centres (vVAC and lVAC). The projections are organised somatotopically in a map with three axes, according to the position of the hair on the leg. First, proximo-distal: afferents from hairs on the proximal leg segments project more anteriorly than do those from hairs on distal leg segments. Moreover, on any given segment the afferents from the more proximal hairs project more anteriorly than do the afferents from the distal hairs. Second, antero-posterior: afferents from hairs on the posterior surface of the leg project more medially than do afferents from anterior hairs. Third, dorso ventral: afferents from hairs on ventral parts of the leg project more ventrally than do afferents from the dorsal hairs. The afferents from posterior and anterior hairs project to an area between the central projections from dorsal hairs and ventral hairs. The position of a projection within the map is dependent upon the location of the hair on the leg and not the peripheral routes taken by the axon of its afferent to reach the ganglion. PMID- 1761739 TI - Prefrontal projections to the mediodorsal nucleus of the thalamus in the rhesus monkey. AB - The corticothalamic projections to the prefrontal cortex have been shown to be topographically organized. However, the underlying basis for this topography as it relates to the organization of the different architectonically defined areas of the prefrontal cortex has not been systematically studied. In the present investigation we have reassessed the thalamic projections from the different architectonic areas of the prefrontal cortex by using the technique of autoradiography in the rhesus monkey. The results show that the prefronto mediodorsal projections are organized according to the architectonic differentiation of the prefrontal cortices. Thus architectonically less differentiated medial and orbital prefrontal regions project to the medial sector of the mediodorsal nucleus, the magnocellular subdivision. In contrast, highly differentiated prefrontal area 8 projects to the most lateral sector of the mediodorsal nucleus, the multiformis subdivision. Lateral prefrontal areas with intermediate architectonic features project to the central parvocellular sector of the mediodorsal nucleus. Additionally, these projections also reveal a dorsoventral topography. Thus areas in the medial and dorsolateral cortices project to the dorsal part of the mediodorsal nucleus. In contrast, areas in orbital and ventrolateral cortices project to the ventral part of the mediodorsal nucleus. The topographic organization of the corticothalamic connections described in this study corresponds to the progressive elaboration and differentiation of the architectonic features of the different prefrontal areas. This successive and dichotomous organization of prefrontothalamic connections may provide the basis for the observed differential functions of the prefrontal cortex and the mediodorsal nucleus. PMID- 1761740 TI - Internuclear neurons in the ocular motor system of frogs. AB - Medial and lateral rectus motoneurons of frogs were localized after retrograde labeling with horseradish peroxidase (HRP) injected in the medial rectus muscle or applied on the cut end of the abducens nerve. Coordinates of these cell columns were used as target areas for the injection of small amounts of HRP (20 60 nl) and [3H]leucine (25-40 nl) and as search areas for retrogradely and anterogradely labeled internuclear neurons (INT) in in vivo and in vitro experiments. HRP injection in the medial rectus subdivision of the oculomotor nucleus (n = 6) resulted in retrograde labeling of cell bodies in the contralateral principal abducens nucleus. On the average about 16 cells per animal were found. Somatic diameters were about 13.5 +/- 2.8 microns (n = 32). The number and the size of these abducens internuclear neurons (AbINT) are smaller than those of lateral rectus motoneurons (n = 75; diameter: 19 +/- 3.2 microns). A crossed projection of AbINT to medial rectus motoneurons in the contralateral oculomotor nucleus is further supported by autoradiographic results. Following injection of [3H]leucine into the abducens nucleus, a high density of silver grains was visible within the contralateral oculomotor nucleus, mainly in the caudal part of the oculomotor nucleus, where medial rectus motoneurons are located. Injection of [3H]leucine in vivo (n = 4) and in vitro (n = 3) resulted in a similar high density of silver grains within the contralateral oculomotor nucleus, but the background level of silver grains was significantly higher after in vitro (264 +/- 38/2,500 microns2) than after in vivo injections (195 +/- 17/2,500 microns2). HRP injection in the principal abducens nucleus (n = 9) resulted in retrograde labeling of cell bodies in the medial rectus subdivisions of the bilateral oculomotor nuclei. Ipsilateral projections predominated, with about 10 (+/- 8) labeled cells over contralateral projections (about 3 +/- 2). Average diameters of these oculomotor internuclear neurons (OcINT) were again smaller (10.8 +/- 2 microns; n = 18) than those of medial rectus motoneurons (14.4 +/- 3 microns; n = 52). In addition, retrogradely labeled cells were consistently encountered in the bilateral vestibular nuclei, the cerebellar nuclei, the dorsal brainstem caudal to the abducens nuclei, and ipsilaterally in the pretectum. Most of the vestibular neurons were located in the rostral part of the vestibular nuclear complex. These neurons might constitute part of the three-neuronal arc of the vestibulo-ocular reflex in the frog. Labeled cells in the pretectum were restricted to the ipsilateral posterior thalamic nucleus (P).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761741 TI - Gliosis during optic fiber regeneration in the goldfish: an immunohistochemical study. AB - Antisera directed against the 48 kDa and 50 kDa cytoskeletal antigens were used to examine changes in the astroglial fabric of the goldfish visual pathways following optic nerve crush. Several major observations are described. First, an optic nerve crush lesion in these animals appears to be devoid of glial cells for at least the first month after surgery. As a corollary, regenerating axons that grow across the lesion may do so over an aglial substrate. Once the axons cross the lesion, their growth is confined to the astroglial domains of the proximal nerve stump. In the optic nerve, gliosis comprises hypertrophy of astrocytic processes such that the open framework characterizing the normal nerve is obscured. In addition, during regeneration, optic nerve glia express large amounts of the 50 kDa cytoskeletal protein, which they ordinarily express at only minimal levels. In the optic tract, gliosis is reflected in a markedly increased expression of the 50 kDa protein as well as an apparent increase in the number and complexity of glial processes. In addition, optic tract glia begin to express the 48 kDa antigen during regeneration. This protein is ordinarily confined for the most part to the optic nerve and is not seen in the tract glia. Finally, no obvious changes were seen in the glia of the optic tectum. These results demonstrate many points of similarity between gliosis in the goldfish and in mammals. However, in some particulars the two responses differ, and it is possible that these differences are related to the differing ability of central axons to regenerate in the two groups of organisms. PMID- 1761742 TI - Organization of callosal connections in the visual cortex of the rabbit following neonatal enucleation, dark rearing, and strobe rearing. AB - The organization of visual callosal projections was studied in (1) normal adult rabbits; (2) adult rabbits which had undergone monocular enucleation (ME) or binocular enucleation (BE) at birth; and (3) adult rabbits which had been deprived of normal visual experience during development by dark rearing (DR) or strobe rearing (SR). Previously published observations (Murphy and Grigonis, Behav Brain Res 30:151, 1988) on callosal organization in adult rabbits in which retinal ganglion cell activity was eliminated during development by intraocular tetrodotoxin (TTX) injections, are also summarized for comparison with these data. The tangential extent of the callosal cell zone was significantly larger than normal in DR, TTX, and ME rabbits, was unchanged in BE rabbits, and was significantly reduced in SR rabbits. An analysis of the laminar distribution of the callosal cells revealed a significant increase in the percentage of callosal cells in lamina IV in ME, DR, and TTX animals. Measurements of density of callosal cells showed a significant increase in the density of the callosal projection in ME and SR rabbits and a decrease in density in BE rabbits compared with normal. The data suggest that the mechanisms involved in the development of the tangential and laminar organization of the callosal cell zone are different. In addition, the data suggest that the mechanisms involved in the maintenance of callosal projections are different from the mechanisms involved in the elimination of callosal projections during development. The effects of these developmental manipulations on callosal organization in other mammals are reviewed and compared with the effects in rabbits. The data suggest that species differences in the degree of maturity of the visual system at birth and in the extent of callosal development at the time of eye opening, may underlie species differences in the effects of these manipulations on the organization of visual callosal projections during development. PMID- 1761743 TI - A synaptic antigen (B16) is localized in retinal synaptic ribbons. AB - This morphological and biochemical study examines the cytoplasmic synaptic determinant recognized by a monoclonal antibody (B16). This antibody was generated by using an immunosuppression protocol that generates antibodies to relatively rare antigens. The B16 antibody labels structures in the brain that are dot-shaped and in the retina that resemble synaptic ribbons in their location, size, developmental emergence, and biochemical composition. The antigen is apparently conserved across species as it is found in retinas from lizards, frogs, fish, birds, mice, rats, rabbits, cats, and monkeys. This paper focuses on observations in the murine retina. Labeling in the outer plexiform layer of the retina is confined to the margin between the outer plexiform layer (OPL) and the outer nuclear layer. The labeled structure resembles a semiellipse or an arc with the open end facing the OPL and the top facing the outer nuclear layer. Overall, the arc is approximately 1 micron in length and less than 0.5 micron thick. Approximately 10% of the labeled arcs occur in a proximal stratum of the OPL and form a planar cluster that resembles a flat plaque parallel to the OPL. Five to ten arcs are found in each plaque. The arcs found within the plaques are approximately 50% smaller than the larger isolated arcs. Counterstaining with peanut agglutinin (PNA), a lectin that recognizes cone photoreceptors and their associated processes, demonstrates that the plaques are associated with the cone pedicles. Animals that have a higher ratio of cones/rods than mice demonstrate a much higher ratio of plaques/isolated arcs in the OPL. The structure labeled in the inner plexiform layer resembles a short bar (0.8 micron long by less than 0.5 micron wide) that is confined to the inner half of the inner plexiform layer in mice. The relative mobility (Mr) of the B16 antigen obtained from mouse retinal and brain tissue is 88 kD, as determined by SDS-PAGE followed by Western blotting. The mouse 88 kD protein is relatively soluble (precipitates at 70% ammonium sulphate) and elutes at a pH of 7.3 from an isoelectric focusing column. It appears that the determinant recognized by the B16 antibody is a previously undescribed synaptic protein that is associated with the synaptic ribbons in photoreceptor and bipolar terminals of most vertebrate retinas. PMID- 1761744 TI - Localization of aspartate-like immunoreactivity in the retina of the turtle (Pseudemys scripta). AB - Aspartate has been reported to be a putative excitatory neurotransmitter in the retina, but little detailed information is available concerning its anatomical distribution. We used an antiserum directed against an aspartate-albumin conjugate to analyze the anatomy, dendritic stratification, and regional distribution of cell types with aspartate-like immunoreactivity in the turtle retina. The results showed dramatic differences in immunoreactivity in the peripheral versus the central retina. Strong aspartate-like immunoreactivity was shown in the peripheral retina, with many well-labeled processes in the inner plexiform layer. Many bipolar, horizontal, amacrine, and ganglion cells, some photoreceptors, and some unidentified cells were strongly immunoreactive in the peripheral retina. In contrast, although the central retina showed well-labeled horizontal cells, there was only light labeling in the inner plexiform layer with weakly immunoreactive amacrine and ganglion cells and no labeled bipolar cells. There were several strongly immunoreactive efferent nerve fibers which left the optic nerve head and arborized extensively in the retina. At the electron microscopic level, electron-dense reaction product was associated with synaptic vesicles at bipolar and amacrine cell synapses in the inner plexiform layer. These results suggest that aspartate may be involved in many diverse synaptic interactions in both the outer plexiform layer and the inner plexiform layer of the turtle retina. PMID- 1761745 TI - Post-rolandic cortical projections of the superior temporal sulcus in the rhesus monkey. AB - The efferent connections of different cytoarchitectonic areas of the superior temporal sulcus (STS) in the rhesus monkey with parieto-temporo-occipital cortex were investigated using autoradiographic methods. Four rostral-to-caudal subdivisions of cortex (area TPO) in the upper bank of the STS have distinct projection patterns. Rostral sectors (areas TPO-1 and -2) project to the rostral superior temporal gyrus (areas Ts1, Ts2, and Ts3), insula of the Sylvian fissure, and parahippocampal gyrus (perirhinal and prorhinal cortexes, areas TF, TH, and TL); caudal sectors (TPO-3 and -4) project to the caudal superior temporal gyrus (areas paAlt and Tpt), supratemporal plane (area paAc), circular sulcus of the Sylvian fissure (area reIt), as well as medial paralimbic (areas 23, 24, and retrosplenial cortex) and extrastriate (areas 18 and 19) cortexes. Area TPO-1 does not project to the parietal lobe; area TPO-2 projects to the inferior parietal lobule; area TPO-3 to the lower bank of the intraparietal sulcus (IPS) (area POa); and area TPO-4 to medial parietal cortex (area PGm). Vision-related cortex (area TEa) in the rostral lower bank of the STS sends fibers to the rostral inferotemporal region (areas TE1, -2, and -3) and parahippocampal gyrus (perirhinal cortex, areas TF and TL). Visual zones in the caudal lower bank and depth of the sulcus (area OAa, or MT and FST) project to the caudal inferotemporal region (areas TE3 and TEO), lateral preoccipital region (area V4), and lower bank of the IPS (area POa). A zone in the rostral depth of the STS (area IPa) projects to the rostral inferotemporal region, parahippocampal gyrus, insula of the Sylvian fissure, parietal operculum, and lower rim of the IPS (area PG). STS projections to parieto-temporo-occipital cortex have "feedforward," "feedbackward," and "side-to-side" laminar patterns of termination similar to those of other cortical sensory systems. The differential connectivity supports the cytoarchitectonic parcellation of the STS and suggests functional heterogeneity. PMID- 1761746 TI - Immunocytochemical localization of argininosuccinate synthetase in the rat brain. AB - The neuronal distribution of argininosuccinate synthetase (ASS) was mapped in the rat brain. Argininosuccinate synthetase is one of the enzymes of the arginine metabolic pathway and catabolizes the synthesis of argininosuccinate from aspartate and citrulline. Since arginine is the precursor of nitric oxide, argininosuccinate synthetase may act as part of the nitric oxide producing pathway. Argininosuccinate is also suggested to have a messenger function in the nervous system. Therefore, the localization of ASS is of great interest. Polyclonal antisera against purified rat liver argininosuccinate synthetase revealed a characteristic distribution pattern of argininosuccinate synthetase like immunoreactivity: (1) many neurons with strong argininosuccinate synthetase like immunoreactivity were observed in the septal area, basal forebrain, anterior medial and premammillary nuclei of the hypothalamus, anterior and midline thalamic nuclei, dorsal endopiriform nucleus of the amygdala, basal nucleus of Meynert, subthalamic nucleus, laterodorsal tegmental nucleus, raphe nuclei, nucleus ambiguus, and the area postrema, (2) neuropile staining was dense in the septal areas, hypothalamus, area postrema, nucleus of the solitary tract, and the laminae I and II of the caudal subnucleus of the spinal trigeminal nucleus and the spinal dorsal horn, (3) relay nuclei of the specific sensory systems such as the dorsal lateral geniculate nucleus and the ventral nuclei of the thalamus were devoid of argininosuccinate synthetase-like immunoreactivity, (4) no staining was seen in the large white matter structures such as the internal capsule, corpus callosum, and the anterior commissure, and (5) most of the neurons stained were small or medium in size and appeared to be interneurons. The results suggest that argininosuccinate synthetase affects the widely distributed, neuromodulatory system in the brain. PMID- 1761748 TI - Evidence for new growth and regeneration of cut axons in developmental plasticity of the rubrospinal tract in the North American opossum. AB - We have shown previously that rubral axons can grow around a lesion of their spinal pathway in the developing opossum and that a critical period exists for that plasticity (Martin and Xu, Dev Brain Res 39:303, 1988). Since most rubrospinal neurons degenerate after axotomy during the critical period, we have proposed that plasticity results primarily from growth of late arriving axons around the lesion rather than regeneration of cut axons (Xu and Martin, J Comp Neurol 279:368, 1989). In the present study, we used a double-labeling paradigm to test that hypothesis. Four groups of pouch young opossums received bilateral or unilateral injections of Fast Blue (FB) into the caudal thoracic or rostral lumbar cord (T12-L2) at different ages in order to label rubrospinal neurons. Three or 4 days later, the rubrospinal tract was transected unilaterally, four to five segments rostral to the injection(s). If the injection was unilateral, the lesion was made ipsilateral to it. The animals were maintained for about 1 month before a second marker, Diamidino Yellow (DY), was injected, usually bilaterally, between the FB injection(s) and the lesion. The animals were maintained for about 5 days before sacrifice and sections through the red nucleus and spinal cord were examined with a fluorescence microscope. During the critical period for plasticity, only a few rubral neurons contralateral to the lesion were labeled by FB alone, supporting our previous contention that most axotomized neurons degenerate. In contrast, many neurons were labeled by DY alone, indicating that their axons were not present in the caudal cord at the time of the FB injection and that they grew around the lesion during the 1 month survival to incorporate DY. A few double-labeled neurons were also found. One interpretation of such neurons is that they survived axotomy, as evidenced by the presence of FB, and supported axons which grew around the lesion to take up DY. Another interpretation is that they supported late growing axons which incorporated residual FB as well as DY. In order to choose between these alternatives, a similar double-labeling paradigm was carried out, but with removal of FB at the time of the lesion. Since a few neurons were still double labeled, we conclude that regeneration of cut axons also contributed to rubrospinal plasticity. Our results support our previous suggestion that developmental plasticity of the rubrospinal tract results primarily from growth of late arriving axons around the lesion, but they also suggest that regeneration of cut axons occurs. PMID- 1761747 TI - Calbindin-like immunoreactivity in the central auditory system of the mustached bat, Pteronotus parnelli. AB - With the aid of a polyclonal antibody specific for Calbindin D-28k, we studied the distribution of this calcium-binding protein in the central auditory system of the mustached bat, Pteronotus parnelli. Components of the cochlear nucleus (CN) that were calbindin-positive (cabp(+] included the root of the auditory nerve, multipolar and globular bushy cells in the anteroventral CN, multipolar and octopus cells in the posteroventral CN, and small and medium-size cells in the dorsal CN. Not stained were spherical bushy cells of the anteroventral CN and pyramidal/fusiform cells in the dorsal CN. In the superior olivary complex, labeled cells were found in the lateral and medial nuclei of the trapezoid body, the ventral and ventromedial periolivary nuclei, and the anterolateral periolivary nucleus. No cellular labeling was seen in the lateral superior olive. In the medial superior olive, only marginal cells were cabp(+). Labeled fibers could be seen surrounding the gosts of unlabeled cells in both the latter nuclei. Most cells in the intermediate nucleus and the columnar division of the ventral nucleus of the lateral lemniscus were cabp(+). However, the dorsal nucleus was cabp(-). A group of cabp(+) cells was also seen in the paralemniscal zone. The inferior colliculus had a relatively low density of cabp(+) cells. Labeled cells were more common in the caudal half of the central nucleus, and in the external nucleus and dorsal cortex. In the auditory thalamus, nearly every cell in the medial geniculate body was cabp(+), but those in the suprageniculate nucleus and in the posterior group did not stain. Small cells in the intermediate layer and giant cells in the deep layers of the superior colliculus were densely cabp(+). In the pons, cabp(+) cells and neuropil could be seen in the medial and lateral pontine nuclei (pontine gray). In conclusion, calbindin-like immunoreactivity was found in most of the brainstem auditory system, as well as in regions associated with acoustic orientation or control of vocalization. However, except for a minority of cells of the medial superior olive, it is conspicuously absent from the nuclei receiving binaural input below the level of the inferior colliculus. PMID- 1761749 TI - Postnatal development of acetylcholinesterase in, and cholinergic projections to, the cat superior colliculus. AB - The postnatal development of cholinergic afferents to the superior colliculus in neonatal cats was studied by using acetylcholinesterase (AChE) histochemistry, choline acetyltransferase (ChAT) immunohistochemistry, and retrograde transport of horseradish peroxidase (HRP). In the adult cat, the pattern of AChE staining was laminar specific. AChE was distributed continuously in the stratum griseum superficiale (SGS) but was organized as patches in the stratum griseum intermediate (SGI). Diffuse AChE staining also was present in the stratum griseum profundum (SGP) and the dorsolateral periaqueductal gray (PAG). At birth, however, AChE staining was barely detectable in the SGS and, aside from a few isolated labeled neurons, was absent from the SGI, SGP, and PAG. By 7 days postnatal (dpn), staining in the SGS was more apparent but did not change appreciably in the deeper laminae. A substantial increase in AChE staining occurred in the SGS at 14 dpn (several days after eye opening), at which time patches in the SGI first became apparent. By 28 dpn, the complete laminar specific adult AChE staining pattern was present, though the staining intensity did not reach the adult level until 56 dpn. A protracted maturation of both AChE staining and ChAT immunoreactivity also was observed in the sources of cholinergic afferents to the superior colliculus, which include the parabigeminal nucleus, and the pedunculopontine (PPN) and lateral dorsal tegmental (LDTN) nuclei. AChE and ChAT-immunoreactive staining in each nucleus was weak at birth but increased during the ensuing 2 weeks. At 21 dpn, however, ChAT immunoreactivity virtually disappeared in the parabigeminal nucleus and significantly decreased in PPN and LDTN. The ChAT immunoreactivity in these nuclei then gradually increased reaching maximum levels by 28 dpn. At 35 dpn, AChE staining showed a significant, though temporary (4 weeks), decrease in the parabigeminal nucleus, but not in the PPN and LDTN, that subsequently increased to the adult level of staining at 70 dpn. The absence of AChE in the SGI in neonatal animals was correlated, at least in part, with a paucity of neurons in the brainstem cholinergic cell groups labeled by retrograde transport of HRP from the superior colliculus. Injections of HRP into the superior colliculus retrogradely labeled many neurons in the parabigeminal nucleus, but few, if any, neurons in the PPN or LDTN at 1 dpn. Retrogradely labeled neurons also were observed in the substantia nigra pars reticulata, albeit fewer in neonates than in adults.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761750 TI - Calcitonin gene-related peptide and corneal innervation: a developmental study in the rat. AB - The development of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerves was studied in neonatal and adult rat corneas stained immunohistochemically according to an avidin biotin peroxidase procedure. At birth, rat corneas already contained dense plexuses of CGRP-LI nerve fibers. Most of the nerves entered the cornea in 12-15 prominent stromal nerve bundles located at regular intervals around the circumference of the cornea. Fibers in these bundles entered the epithelium approximately midway between the limbus and the center of the cornea and supplied extensive central and pericentral areas of the tissue. In addition, smaller numbers of axons entered the cornea individually and in small fascicles located in between the larger bundles and supplied mainly peripheral territory. In the epithelium, the CGRP-LI nerves formed a complex, highly anastomotic meshwork that ramified uniformly throughout central and peripheral areas of the tissues. Fibers in the plexus gave origin to numerous short, stout terminal axons that extended into the adjacent epithelium in all directions with no preferred orientation. During the first week of neonatal life, several changes in CGRP-LI innervation occurred: 1) the innervation density of the central and pericentral cornea increased relative to the peripheral cornea; 2) intraepithelial axons became progressively longer, increased in branching complexity, and oriented preferentially towards the center of the cornea; and 3) a dense innervation of the corneoscleral limbus and, in particular, the branches of the marginal artery, developed. Midway through the second week of life, immature versions of corneal epithelial "leashes," the dominant feature of the adult corneal innervation, were first observed. Over the next 10 days, the leash formations in the central and pericentral cornea gradually became more complex and gave rise to greater numbers of terminal axons, compared to developing leashes in the peripheral cornea. The mature pattern of corneal CGRP-LI innervation was reached on day 21 and remained constant (except for compensatory growth-related elongation of axons) for at least the first 6 months of life. Transection of the ophthalmomaxillary nerve or neonatal administration of the sensory neurotoxin capsaicin resulted in the total loss of CGRP-LI staining from the cornea. In contrast, removal of the superior cervical ganglion had no effect on corneal CGRP-LI staining. The extraordinary density and complexity of the CGRP LI innervation of the rat cornea demonstrated at all stages of development in this study suggests that these nerves may play important roles in corneal sensory, reflex, and trophic functions. PMID- 1761751 TI - Functional regions within the map of a single digit in raccoon primary somatosensory cortex. AB - Electrophysiological recordings were made at a large number of sites in the primary somatosensory cortex of six anesthetized raccoons. A high density of penetrations (110-229 per animal), within or near the representation of the fourth digit, allowed identification of three cortical regions with different physiological properties: a glabrous zone, containing a highly detailed, somatotopically ordered representation of the glabrous surface of the digit; rostral to this a claw-dominant zone, in which the neurons at most penetrations respond to stimulation of the claw of the fourth digit, but may also receive input from the hairy skin or surrounding glabrous skin; and a more rostral multidigit zone, in which the neurons respond to stimulation of two to five digits, with the dominant digit usually being the one represented caudally (i.e., the fourth digit at most of the sites sampled here). Claw-dominant zones with receptive fields restricted to digit three or five are also found rostral to the representations of the glabrous skin of the corresponding digit. The glabrous and claw-dominant zones constitute a complete map of the fourth digit. The multidigit region presumably is a separate map, since its neurons have different spatial convergence, higher thresholds, and a lower incidence of slowly adapting inputs than those in the claw-dominant and glabrous zones. A comparison between animals with lesions of the basal forebrain and intact animals found no differences in the organization of these zones or in the responses to peripheral input, suggesting that cholinergic inputs to the cortex are not essential to these properties. The detailed description of these regions and the proposed terminology should resolve some inconsistencies in the use of the term "heterogeneous zone" in this species. PMID- 1761752 TI - Parvalbumin- and calbindin D28k-immunoreactive neurons in the hippocampal formation of the macaque monkey. AB - Calcium-binding proteins calbindin D28k (CaBP) and parvalbumin (PV) were localized in neurons of the monkey hippocampal formation. CaBP immunoreactivity is present in all granule cells and in a large proportion of CA1 and CA2 pyramidal neurons, as well as in a distinct population of local circuit neurons. In the dentate gyrus, CaBP-immunoreactive nongranule cells are present in the molecular layer and in the hilar region, but they do not include the pyramidal basket cells at the hilar border. In the Ammon's horn, CaBP-positive, nonpyramidal neurons are more frequent in the CA3 area than in any other parts of the hippocampal formation. They are concentrated in the strata oriens and pyramidale of areas CA1-3, whereas only a few small neurons were found in the strata lucidum and radiatum of CA3 and in the stratum moleculare of the CA1 area. PV is exclusively present in local circuit neurons both in the dentate gyrus and in Ammon's horn. In the dentate gyrus the presumed basket cells at the hilar border exhibit PV immunoreactivity. In the hilar region and molecular layer only a relatively small number of cells are immunoreactive for PV. Most of these PV positive cell bodies are located in the inner half of the molecular layer, with occasional horizontal cells at the hippocampal fissure. In Ammon's horn, strata oriens and pyramidale of areas CA1-3 contain a large number of PV-positive cells. There are no PV-immunoreactive cells in the strata lucidum, radiatum, or lacunosum moleculare. The CaBP- and PV-containing neurons form different subpopulations of cells in the monkey hippocampal formation. With the exception of a basket cell type in the monkey dentate gyrus, the CaBP- and PV-positive cell types were found to be remarkably similar in rodents and primates. PMID- 1761753 TI - A light and electron microscopic study of the development of the Mauthner cell and vestibular nerve in the axolotl. AB - Vestibular axons form synapses on a restricted area of the lateral dendrite of the Mauthner cell, a large, identified brainstem neuron found in fish and amphibians. The differentiation of the vestibular nerve, medullary neuropil, and Mauthner cell of the axolotl (Ambystoma mexicanum) was studied to understand better the means by which this synaptic specificity arises. The Mauthner cell first extends a medial process and then a lateral dendrite. The latter initially elongates as a simple process and later sends out branches. As the lateral dendrite grows, vestibular axons enter the brainstem to form one of the earliest of several discrete axon fascicles that course longitudinally through the neuropil. The fascicles, many of which are identifiable on the basis of their location and axonal morphology, are the precursors of the longitudinal tracts of the mature salamander. The lateral dendrite grows dorsally over the orthogonally oriented fascicles, making contact with each at a characteristic time and place. The first afferents to form synapses do so on the soma and proximal lateral dendrite; subsequent afferent groups terminate more distally. Axons within a given fascicle form synapses with the Mauthner cell in a discrete and initially homogeneous domain. As dendritic branches form and the organization of the longitudinal fascicles becomes more complex, the homogeneity of axons terminating on a given region of the Mauthner cell surface is lost, but no major rearrangement or migration of terminals is apparent. These observations are consistent with both active recognition and passive spatiotemporal models of synaptic site specificity. PMID- 1761754 TI - Specific temporal and spatial distribution of JUN, FOS, and KROX-24 proteins in spinal neurons following noxious transsynaptic stimulation. AB - We present the first comparative investigation of the basal and transsynaptically induced expression of c-JUN, JUN B, JUN D, c-FOS, FOS B, and KROX-24 proteins in the spinal cord, using immunocytochemistry with specific antibodies. We demonstrate that electrical stimulation of the sciatic nerve at A delta/C-fiber (not A alpha/beta-fiber) intensity strongly induces the expression of these immediate-early gene-encoded proteins. Basal immunoreactivity was found for c-JUN in motoneurons, for JUN D in almost every cell of the gray matter, and for KROX 24 in the superficial dorsal horn. One hour after electrical stimulation of the sciatic nerve at A delta/C-fiber intensity, expression of all proteins except JUN D reached its maximum. Initially immunoreactivity was restricted to the ipsilateral dorsal horn, but after 4 hours appeared contralaterally. Expression of JUN D was increased only after 4 hours. Within the dorsal horn, the expression of c-JUN, JUN B, FOS B, and KROX-24 was mainly restricted to the superficial layers. Immunoreactivity decreased to basal levels between 8 and 16 hours. c-FOS and JUN D were expressed in both the superficial and deep dorsal horn; in the latter, c-FOS and JUN D persisted longer. Induced JUN D was present the longest and was still visible after 32 hours. In motoneurons of the ipsilateral ventral horn, c-JUN, JUN D, and c-FOS appeared after 8 hours. Surgical exposure of the sciatic nerve evoked a strikingly prolonged expression of all proteins compared to that following electrical stimulation of the sciatic nerve. Our results demonstrate that stimulation of nociceptive A delta- and C-fibers induces early and late expression of proteins encoded by immediate-early genes with a specific temporal and spatial distribution of the expression of each protein. Furthermore, the extent of protein expression reflects the intensity of noxious stimulation. PMID- 1761755 TI - Effect of precocious and delayed afferent arrival on synapse localization on the amphibian Mauthner cell. AB - Afferents often form synapses on restricted regions of their target cells. The connections between vestibular axons and the Mauthner cell are an example of this sort of specificity. The Mauthner cells are a pair of identifiable central neurons in certain fish and amphibians. In the axolotl (Ambystoma mexicanum), the large vestibular axons form club endings on only one portion of one dendrite of the Mauthner cell. During development, this specific distribution might result from nothing more than when and where the growing axons and dendrite meet (spatiotemporal model). Alternatively, the distribution might reflect constraints on where the developing axons may grow (axon segregation model) or form synapses (active recognition model). As a test of the spatiotemporal model, ears and vestibular ganglia from older embryos (Harrison stage 33/34-) were unilaterally grafted in place of prospective ear/ganglion placodes of younger embryos (stage 23). Light and electron microscopic examination revealed that the axons precociously entered the brain and formed synapses on the Mauthner cell. Similarly, grafts from younger to older embryos resulted in a delay. In both situations, mapping the club endings on the mature Mauthner cells of 21-mm larvae revealed a distribution similar to that of the contralateral control cells. Thus precocious and delayed afferent arrival did not alter the eventual localization of the synapses. These results conflict with the spatiotemporal model and imply that the vestibular axons are either restricted to a certain region of the neuropil or capable of recognizing a specific region of the Mauthner cell surface. PMID- 1761756 TI - Diverse thalamic projections to the prefrontal cortex in the rhesus monkey. AB - We studied the sources of thalamic projections to prefrontal areas of nine rhesus monkeys with the aid of retrograde tracers (horseradish peroxidase or fluorescent dyes). Our goal was to determine the proportion of labeled neurons contributing to this projection system by the mediodorsal (MD) nucleus compared to those distributed in other thalamic nuclei, and to investigate the relationship of thalamic projections to specific architectonic areas of the prefrontal cortex. We selected areas for study within both the basoventral (areas 11, 12, and ventral 46) and the mediodorsal (areas 32, 14, 46, and 8) prefrontal sectors. This choice was based on our previous studies, which indicate differences in cortical projections to these two distinct architectonic sectors (Barbas, '88; Barbas and Pandya, '89). In addition, for each sector we included areas with different architectonic profiles, which is also relevant to the connectional patterns of the prefrontal cortices. The results showed that MD included a clear majority (over 80%) of all thalamic neurons directed to some prefrontal cortices (areas 11, 46, and 8); it contributed just over half to some others (areas 12 and 32), and less than a third to area 14. Clusters of neurons directed to basoventral and mediodorsal prefrontal areas were largely segregated within MD: the former were found ventrally, the latter dorsally. However, the most striking findings establish a relationship between thalamic origin and laminar definition of the prefrontal target areas. Most thalamic neurons directed to lateral prefrontal cortices, which are characterized by a high degree of laminar definition (areas 46 and 8), originated in the parvicellular and multiform subdivisions of MD, and only a few were found in other nuclei. In contrast, orbital and medial cortices, which have a low degree of laminar differentiation, were targeted by the magnocellular subdivision of MD and by numerous other limbic thalamic nuclei, including the midline and the anterior. Thus topographic specificity in the origin of thalamic projections increased as the laminar definition of the target area increased. Moreover, the rostrocaudal distribution of labeled neurons in MD and the medial pulvinar also differed depending on the degree of the laminar definition of the prefrontal target areas. The rostral parts of MD and the medial pulvinar projected to the eulaminate lateral prefrontal cortices, whereas their caudal parts projected to orbital and medial limbic cortices. Selective destruction of caudal MD is known to disrupt mnemonic processes in both humans and monkeys, suggesting that this thalamic-limbic prefrontal loop may constitute an important pathway for memory. PMID- 1761757 TI - Differential expression of mRNAs for the NGF family of neurotrophic factors in the adult rat central olfactory system. AB - The cellular localization of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), in the rat central olfactory system was evaluated with in situ hybridization of 35S-labeled cRNA probes. In the main olfactory bulb, low levels of NGF and BDNF mRNA expression were detected. NGF mRNA was restricted to the glomerular region while BDNF mRNA was predominantly localized to the granule cell layer. No cellular hybridization to NT3 cRNA was seen. The accessory olfactory bulb did not express detectable levels of mRNA for any of the three related neurotrophic factors. Areas which receive olfactory bulb afferents expressed comparatively high levels of both NGF and BDNF mRNA. Cell labeling with cRNAs for NGF and BDNF occurred throughout the cellular layers of the anterior olfactory nucleus and in layers 2 and 3 of rostral piriform cortex. BDNF mRNA expression in these areas appeared more robust than that of NGF mRNA, while NT3 mRNA was not detectable. In contrast, tenia tecta exhibited dense labeling with the cRNAs for all three neurotrophic factors. The localization of NGF mRNA to primary target neurons of the olfactory nerve in the periglomerular region of the main olfactory bulb suggests that bulb cells may influence the ingrowth and continual turnover of olfactory sensory afferents. However, as there is a strong correlation between the distribution of neurotrophic factor mRNAs within rostral olfactory structures and the distribution of centrifugal cholinergic afferents, it is more likely that bulb derived NGF, and possibly BDNF, act on the cholinergic neurons of the basal forebrain. PMID- 1761758 TI - Experimental hypophosphataemia in growing pigs: effects on endochondral ossification in comparison to osteochondrosis. AB - Hypophosphataemia was induced in growing pigs by dietary supplementation with aluminium hydroxide. The effect on endochondral ossification was studied morphologically in comparison with normophosphataemic pigs given aluminium phosphate or left untreated. The aim of the investigation was to elucidate further the role of nutritional factors in the pathogenesis of disturbed endochondral ossification, occurring in osteochondrosis. In all pigs, focal arrestment of endochondral ossification with subsequent cartilage retention in the epiphyseal or metaphyseal growth zones was seen. In normophosphataemic pigs, focal degenerative cartilage changes were associated with impairment of vascular penetration. The lesions had morphological characteristics of early osteochondrosis. In hypophosphataemic pigs, a more generalized disturbance, endochondral ossification, was seen with impaired vascular penetration and excessive deposition of osteoid in the primary spongiosa. Focal cartilage retentions were associated with necrotic changes in the primary spongiosa and not with cartilage degeneration. The lesions were similar to rickets and it was concluded that hypophosphataemia is not an aetiological factor in the development of osteochondrosis. The differentiation between the cartilage retention seen in early stages of osteochondrosis and rickets must be based on histological examination. PMID- 1761759 TI - Hepatic pathology of the colon carcinogen, azoxymethane, in Hanford-Moore miniature pigs. AB - Azoxymethane (AOM) is commonly used in colon carcinogenesis studies in rodents. In an attempt to develop a large animal model of human colon cancer, AOM was given to Hanford-Moore miniature pigs. Six pigs were injected intraperitoneally with a single dose of AOM of either 5, 10, 20, 40 or 55 mg per kg body weight. Within 48 h, severe signs of toxicity and death occurred in animals receiving greater than 20 mg per kg AOM. After 30 days, all surviving animals were killed and necropsied. Acute hepatic necrosis with haemorrhage was the major toxic effect of AOM in all animals receiving doses exceeding 20 mg per kg. In a second, longer-term experiment, eight pigs were injected with either 20 mg per kg AOM weekly or 10 mg per kg AOM every other week or a combination of both treatments. Chronic toxic effects were limited to the liver. No colon tumours were observed. It is concluded that this particular species demonstrates marked hepatic sensitivity to the toxic effects of AOM. PMID- 1761760 TI - Bovine farcy: a clinico-pathological study of the disease and its aetiological agent. AB - An extensive survey for bovine farcy covering 14,192 animals was conducted in the Sudan. The incidence of the disease was 31.9 per cent in Western Sudan which is regarded as an endemic area. Animals were examined clinically and at post-mortem. The lesions involved the prescapular, femoral, parotid, retropharyngeal, submaxillary, inguinal and mediastinal lymph nodes. Some animals had farcy lesions in the udder and some developed the pulmonary form of the disease. The disease is slow, but progressive in nature and was more prevalent among adult cattle than calves. Mycobacterium farcinogenes was found to be the cause of bovine farcy in the Sudan. The morphological and biochemical characteristics, and the mycolic acid content of the isolated strains were found to be identical to the reference strains of M. farcinogenes and were quite different from reference strains of Nocardia farcinica from which they were easily distinguished by the presence of alpha-mycolate, alpha'-mycolate and epoxymycolate in M. farcinogenes. Hydrolysis of mycolic acids with tetrabutylammonium hydroxide and the precipitation with toluene and acetonitrile gave good results comparable with acid methonalysis and alkaline hydrolysis. Precipitin lines were detected in the sera of some farcy-infected cattle. Histopathological examination of farcy lesions revealed a severe granulomatous reaction characterized by lymphocyte, macrophage, epithelioid and giant cell infiltration as well as marked fibrous proliferation. These changes were indicative of a progressive disease of the delayed tuberculin hypersensitivity type. PMID- 1761761 TI - Chronic lesions of thrombo-embolic meningo-encephalomyelitis in calves. AB - Six calves showed neurological signs with recumbency for 5 to 30 days. Histologically, they had encephalomyelitis characterized by multiple minute foci of malacia and perivascular microgliosis throughout the central nervous system. Widespread degeneration of the white matter was also detected mainly in the spinal cord. Micro-abscesses and thrombophlebitis, which were occasionally observed in the malacic lesions, suggested that the disease was a feature of infectious thrombo-embolic meningo-encephalomyelitis modified by various factors, including antibiotic therapy. PMID- 1761762 TI - Increased susceptibility of aged rats to haemorrhage and intravascular hypercoagulation following endotoxin administered in a generalized Shwartzman regime. AB - Ageing rats are known to have an increased incidence of myocardial fibrosis and dyspnoea caused by pulmonary intravascular coagulation. In order to determine whether endotoxin can be responsible for such responses in ageing rats we have exposed rats of differing ages (2 months, 16 months and 24 months) to single or repeated (two doses 24 h apart; generalized Shwartzman regime) intravenous doses of endotoxin (E. coli 0111 B4). Only the 2-year-old rats reacted adversely. Two doses of endotoxin produced death, with focal myocardial necrosis, haemorrhage and pulmonary and hepatic intravascular coagulation. The increased susceptibility of aged rats to the toxic effects of endotoxin explains some of the changes found in the tissues of old rats. The sporadic nature of both cardiac failure and dyspnoea as a cause of morbidity and mortality in ageing rats may be related to the need for two endotoxin episodes in a period of 24 h to provoke a generalized Shwartzman reaction, an occurrence likely to be relatively uncommon under natural conditions. PMID- 1761763 TI - AA-like amyloid deposits confined to arthritic joints in two dogs with rheumatoid arthritis. AB - Two dogs with clinical, serological, radiographic and pathological changes similar to those of rheumatoid arthritis of man and a previously undescribed pattern of amyloid deposits are described. As revealed by light and electron microscopical investigations, amyloid fibrils were found exclusively in articular tissue structures of arthritic joints and in one tonsil of one dog. Based on our immunohistochemical results, the amyloid protein is believed to be of a local AA type. PMID- 1761764 TI - Minimal focal dermal hypoplasia in a man: a case of father-to-daughter transmission. AB - Focal dermal hypoplasia is a rare genetic disorder characterized by diffuse and specific cutaneous lesions. Multiple visceral abnormalities are frequently associated. A minimal form of the disease (only cutaneous and localized to one thigh) is reported in the father of a woman who had typical focal dermal hypoplasia. PMID- 1761765 TI - Intravascular coagulation necrosis of the skin associated with cryofibrinogenemia, diabetes mellitus, and cardiolipin autoantibodies. AB - Intravascular coagulation necrosis of the skin is rare and appears as hemorrhagic infiltrates that may develop ulcerating necrosis, mainly on the acral areas. The face, arms, and legs were severely involved in our patient. In this patient intravascular coagulation necrosis was associated with cryofibrinogenemia, diabetes mellitus, and IgM cardiolipin autoantibodies. In addition, rheumatoid factor, elevated polyclonal IgA, and haptoglobin were present as risk factors for the vasculopathy. Skin biopsy specimens showed plugging of dermal venules by thrombi formed of fibrin and erythrocytes. Immunohistologic staining revealed a strong positive reaction for fibrinogen, with some positivity for C3, C4, IgG, IgA, and IgM. Erythrocyte extravasation occurred in late lesions without being accompanied by perivascular leukocytic infiltrates. Detailed clinical examination failed to identify an underlying malignancy. Treatment with heparin and prednisolone produced only a brief remission. However, the combination of chlorambucil (7 mg/day orally) with low-dose oral prednisolone (10 mg/day) for several weeks controlled the disease and greatly reduced the cryofibrinogen. No relapse occurred after discontinuation of treatment. PMID- 1761766 TI - Hydroa vacciniforme: an unusual clinical manifestation. AB - Hydroa vacciniforme is a rare, chronic photodermatosis with onset in childhood that is characterized by recurrent vesiculation, necrosis, and vacciniform scarring limited to sun-exposed skin. We report a case of nonvesicular hydroa vacciniforme in which only extensive crusting associated with hypertrophic scarring on sun-exposed skin was present. Multiple exposures to UVA, however, reproduced lesions with the typical clinical and histologic features of hydroa vacciniforme. Results of blood, urine, and fecal porphyrin studies were normal. PMID- 1761767 TI - Cystic fibrosis presenting with periorificial dermatitis. AB - A 2-week-old baby boy had a periorificial dermatitis that progressively worsened, as did his failure to thrive. Decreased serum zinc, proteins, and amino acids, as well as an increase in fecal fat, were noted. The child's dermatitis responded promptly to nutritional therapy. Sweat chloride levels were markedly elevated. The dermatitis, occasionally seen as a presenting feature of cystic fibrosis, is most likely the result of malabsorption caused by pancreatic exocrine dysfunction. PMID- 1761768 TI - Alopecia of myxedema: clinical response to levothyroxine sodium. AB - Noncicatricial alopecia resulting from myxedema developed in a 58-year-old woman. We report the response of her alopecia to treatment with levothyroxine sodium and review the literature on the subject. PMID- 1761769 TI - Large-cell lymphoma presenting with a distinctive inflammatory dermatosis. AB - Severe, progressively enlarging inflammatory plaques of the upper trunk and neck developed in a 12-year-old girl. Histologic examination revealed a unique inflammatory cell infiltrate that consisted of chronic inflammation in the dermis subtending spongiosis with a diffuse neutrophilic epidermal infiltrate. A tumor in the right axilla was found by computed tomography. Tissue obtained at open biopsy examination demonstrated a large-cell lymphoma of B-cell origin. The tumor and dermatosis responded dramatically to chemotherapy. The distinctive histologic pattern and clinical course suggest that this dermatosis may represent an unusual paraneoplastic presentation of large-cell lymphoma. PMID- 1761770 TI - Cutaneous reaction from a broken thermometer. AB - A cutaneous and soft tissue reaction that resulted from a broken thermometer inside the mouth of a 10-year-old boy is described. Metallic mercury globules and glass pieces were identified in the excised tissue. On histologic examination, a zone of necrosis, polymorphonuclear leukocytes, macrophages, and multinucleated giant cells surrounded metallic mercury that appeared as dark opaque globules. Dense fibrosis and reactive lymphoid hyperplasia were also noted in the dermis and deeper tissues. The gold lysis test, scanning electron microscopy, and energy dispersive x-ray analysis confirmed the presence of mercury in the tissue. A literature review on cutaneous mercury granuloma illustrates its unpredictable course. The cutaneous reaction may remain localized, but some cases are associated with an elevated mercury level in blood and urine, pulmonary embolism, mercury poisoning, and even with fatal outcome. Various manifestations of mercury poisoning and guidelines for the management of cutaneous mercury granuloma are discussed. PMID- 1761771 TI - Treatment of necrolytic migratory erythema in glucagonoma syndrome. AB - The glucagonoma syndrome is characterized by elevated serum glucagon, a pancreatic alpha-cell tumor, anemia, hypoaminoacidemia, and necrolytic migratory erythema. Necrolytic migratory erythema may cause marked morbidity and is frequently misdiagnosed. A 42-year-old white woman with a 1 1/2-year history of refractory dermatitis (most severe on the lower extremities) had the glucagonoma syndrome. Her severe morbidity was markedly relieved with the administration of intravenous amino acids. This therapy was successful in controlling the necrolytic migratory erythema through recurrences after somatostatin (SMS 201 995), surgical debulking, and chemotherapy proved inadequate. PMID- 1761772 TI - An unusual presentation of fixed cutaneous sporotrichosis: a case report and review of the literature. AB - Sporotrichosis is extremely rare in infants. This report describes an 84-day-old girl with fixed cutaneous sporotrichosis, presumably transmitted by a cat. A rapid, complete response to a low dose of oral potassium iodide therapy was attained. To our knowledge, this is the youngest reported patient with sporotrichosis, as well as the lowest effective daily dose of potassium iodide. PMID- 1761773 TI - Nodular cutaneous B-cell lymphoma of the scalp in the acquired immunodeficiency syndrome. AB - Aggressive B-cell non-Hodgkin's lymphoma frequently complicates human immunodeficiency virus type 1 infection. Although extranodal disease is an important feature of this condition, the incidence of cutaneous involvement has not been determined. A review of 754 published cases of B-cell non-Hodgkin's lymphoma associated with human immunodeficiency virus type 1 revealed an incidence of cutaneous extranodal involvement of 8.2%, approximately equal to that seen in non-Hodgkin's lymphoma not associated with human immunodeficiency virus. Lymphoma was the initial manifestation of acquired immunodeficiency syndrome in two thirds of these cases. In particular, although the head and neck are commonly involved in non-Hodgkin's lymphoma not associated with human immunodeficiency virus, scalp involvement is uncommon in human immunodeficiency virus-associated B-cell non-Hodgkin's lymphoma, and we report the second case. The natural history and proposed pathogenesis of human immunodeficiency virus associated non-Hodgkin's lymphoma are discussed. PMID- 1761774 TI - Linear and punctate porokeratosis associated with end-stage liver disease. AB - A periodic eruption of porokeratosis developed in a 31-year-old black woman with chronic idiopathic hepatitis requiring liver transplantation. The clinicopathologic features were chiefly those of linear and punctate porokeratosis but overlapped those of porokeratosis plantaris, palmaris et disseminata and hyperkeratotic or verrucous porokeratosis. Typical cornoid lamellae were visible on histologic examination. Outbreaks of the lesions occurred during exacerbations of the liver disease. The skin condition rapidly improved after operation, with concomitant improvement in liver function. PMID- 1761775 TI - Eruptive epidermal cysts and multiple squamous cell carcinomas after therapy for cutaneous T-cell lymphoma. AB - Both topical nitrogen mustard and psoralen photochemotherapy may induce benign and malignant alterations in the skin. We describe the explosive appearance of multiple epidermal cysts and squamous cell carcinomas in a patient whose cutaneous T-cell lymphoma was treated sequentially with these two types of therapy. This is the first report of both processes in the same patient with cutaneous T-cell lymphoma. It strongly supports the concept of lesion induction, while raising the question of an additive or even synergistic effect of these types of therapy. PMID- 1761776 TI - Role of tumor necrosis factor-alpha in Sneddon-Wilkinson subcorneal pustular dermatosis. A model of neutrophil priming in vivo. AB - A patient with IgG-kappa-associated subcorneal pustular dermatosis (Sneddon Wilkinson disease) refractory to dapsone, etretinate, and plasma exchange was successfully treated with corticosteroids. A study of neutrophils from both blood and pustules was carried out before and during treatment. Levels of tumor necrosis factor-alpha were measured in serum, pustules, content, and supernatant of monocytes. The results suggest that a hyperactivation of neutrophils in the skin is due at least partly to excessive production of tumor necrosis factor alpha. PMID- 1761777 TI - Multiple cutaneous reticulohistiocytomas (reticulohistiocytic granulomas). AB - Multiple cutaneous reticulohistiocytomas (reticulohistiocytic granulomas) represent a unique pattern in the spectrum of the reticulohistiocytoses. Seven cases have been reported in the English-language literature. A case of multiple cutaneous reticulohistiocytomas observed for 5 years is presented. The spectrum of the reticulohistiocytoses is reviewed, and the distinct clinical patterns of the disease are compared. PMID- 1761778 TI - Evidence for percutaneous inoculation as the mode of transmission for chromoblastomycosis. AB - The exact pathogenesis of chromoblastomycosis is unknown. Direct percutaneous inoculation, inhalation, and hematogenous dissemination have been implicated. We report a case of chromoblastomycosis that followed a well-defined episode of penetrating trauma. The causative organism, Fonsecaea pedrosi, was cultured from the patient's lesion and from the tree branch responsible for the trauma. This "natural" experiment supports the contention that one cause of chromoblastomycosis is traumatic cutaneous implantation of the fungus. PMID- 1761779 TI - Castleman's disease associated with pemphigus vulgaris. AB - Castleman's disease is a rare, benign, lymphoproliferative disorder of unknown cause. The hyaline-vascular type is frequently associated with a localized mediastinal mass. The plasma-cell type is associated with constitutional symptoms, multicentric lymph node involvement, lymphoma development, and autoimmune disease-like laboratory abnormalities such as elevated erythrocyte sedimentation rate, anemia, and thrombocytopenia. We report a case of hyaline vascular Castleman's disease associated with a cutaneous autoimmune disease, pemphigus vulgaris. We also reviewed the clinicopathologic features of four similar cases. Among these five reports of Castleman's disease, five patients had severe erosive stomatitis diagnosed as oral pemphigus, three had keratoconjunctivitis, and three had circulating pemphigus antibodies. All were young, ranging in age from 15 to 21 years, and four of the five were women. Two had hyaline-vascular Castleman's disease, whereas three had plasma-cell Castleman's disease. All five had surgical resection of the Castleman's disease mass. After surgery, remission of pemphigus vulgaris could be achieved with reduced dosages of steroids in all cases. In at least two cases steroid treatment could be completely discontinued. We postulate that an underlying immune dysfunction in Castleman's disease facilitates the expression of pemphigus. PMID- 1761780 TI - Are stem cells attacked in graft-versus-host disease? PMID- 1761781 TI - HMB-45: a clue to the biology of malignant melanoma? PMID- 1761782 TI - Cytotoxic folliculitis in GvHD. Evidence of follicular stem cell injury and recovery. AB - Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undifferentiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease, which peaked during the fourth week post-transplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, greater than 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761783 TI - HMB-45 monoclonal antibody recognizes an inducible and reversible melanocyte cytoplasmic protein. AB - HMB-45 is a monoclonal antibody directed against human melanoma cells and which stains epidermal and dermal melanoma cells, the junctional components of common and dysplastic melanocytic nevi, and melanocytes in fetal skin. In addition, melanocytes in a variety of reactive conditions have been shown to label with HMB 45, as have dermal melanocytes within Spitz and dysplastic nevi. No melanocytes in normal adult epidermis or in the dermis of common nevi have stained with HMB 45. In order to better understand the properties of this antibody, and of the melanocytes that react with it, we stained cultured human melanocytes grown in a variety of conditions. Melanocytes from human foreskins were grown for 2-3 weeks in MCDB 153 medium supplemented with insulin, epidermal growth factor, and bovine pituitary extract as a mixed population of keratinocytes and melanocytes. Some cells were transferred to basal medium MCDB 153 (unsupplemented) for periods ranging from 3-5 days, and a subset of these were returned to growth-factor supplemented medium. In all cases, S100 staining was used to confirm the presence of melanocytes. Melanocytes grown in complete medium showed strong granular cytoplasmic staining with HMB-45. Cells transferred to basal medium showed a markedly diminished staining intensity which was reversible within 3 days upon return of the cells to complete medium. The findings suggest that expression of the protein recognized by HMB-45 may be related to a growth factor present in complete medium, but missing from basal MCDB 153.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761784 TI - Transient bullous dermolysis of the newborn. Case report and review of pathogenesis. AB - A case of transient bullous dermolysis of the newborn is reported. A healthy Hispanic newborn developed bullae during the first two days of life. From age two to four weeks, the lesions healed with milia formation. There was no residual scarring or hypopigmentation. An induced blister showed dermal-epidermal separation with the PAS-positive basement membrane in the epidermal roof. PAS positive inclusions were present in the cytoplasm of a few basal cells. Examination by electron microscopy showed degeneration of the collagen and anchoring fibrils. There were numerous stellate inclusions in the endoplasmic reticulum of the cytoplasm of the lesional basal keratinocytes. PMID- 1761785 TI - Neonatal lupus erythematosus syndrome. AB - Three cases of neonatal lupus erythematosus (NLE) syndrome are described. The key diagnostic sign is the erythematous and annular clinical appearance of lesions. The histopathologic findings may be subtle in NLE syndrome compared with discoid or subacute cutaneous lupus erythematosus. Direct immunofluorescence testing may be useful in supplementing the histopathologic evaluation. Detection of immunoglobulins, complement, or both at the basement membrane zone in lesional skin by immunofluorescence occurs in approximately half of cases; a negative study does not preclude the diagnosis of NLE syndrome. Clinical and serologic evaluation of both the infant and the mother are important in establishing a diagnosis of NLE syndrome, particularly when histopathologic findings are subtle. PMID- 1761786 TI - Localized epidermal necrolysis (erythema multiforme-like reaction) following intravenous injection of vinblastine. AB - We report a case of localized epidermal necrolysis that developed 24 hours after an intravenous injection of vinblastine. Clinically, the lesions consisted of erythematous macules, vesicles, and bullae with a linear arrangement over the injected vein. Histologically, the lesions showed features closely resembling erythema multiforme (epidermal necrolysis). We discuss the pathogenesis of this curious cutaneous drug reaction and review the literature concerning local cutaneous complications associated with intravenously administered chemotherapeutic agents. PMID- 1761787 TI - Ultrastructural signs of altered intracellular metabolism in acral persistent papular mucinosis. AB - An asymptomatic 24-year-old woman presented with multiple discrete papules on the extensor surfaces of the hands and wrists. Light microscopy revealed focal increase in the amount of dermal fibroblasts as well as deposition of hyaluronidase-labile mucoid substance. The collagen and elastin were decreased. The changes were consistent with acral persistent papular mucinosis (APPM). In electron microscopy, the intercellular glycosaminoglycans showed small ruthenium red-positive granules and thin filaments indicating normal morphology. The fibroblastic cells, however, were conspicuously altered. Endoplasmic reticulum was dilated, cytoplasm contained large amounts of osmiophilic, concentric lysosomal structures, and there was distinct fibrous lamina in the nuclear membrane. It was concluded that the primary event in APPM probably affects the intracellular metabolism of the dermal fibroblast. The accumulation of lysosomal structures may be a distinct feature of APPM differentiating it from the other reactive cutaneous mucinoses, or it may only reflect nonspecific degeneration in a long-standing lesion. PMID- 1761788 TI - Collagenous and elastotic marginal plaques of the hands (CEMPH) PMID- 1761789 TI - Immunological effects of ultraviolet radiation. PMID- 1761790 TI - Skin organogenesis in vitro: a new tool for dermatology. PMID- 1761791 TI - Dermatophytosis in children and adolescents: epidemiological, clinical, and microbiological aspects changing with age. AB - During a four year period, a total of 84 cases of dermatophytosis were seen in patients from 0 to 17 years of age attending our out-patient department. The sex distribution was about equal in preadolescents. Males predominated among adolescents. A peak incidence at early school age was due to cases of tinea capitis, mainly caused by Microsporum canis. A peak among adolescents was due to cases of tinea pedis, mainly caused by Trichophyton rubrum. In general, patients with Trichophyton rubrum infections were older than those with other types of dermatophytosis (p less than 0.05). Dermatophytosis due to Microsporum canis was most frequently seen in January and in September (p less than 0.01). Although onychomycosis due to dermatophytes was a comparatively rare disease, it did occur within all age subgroups. Entities which were very frequent in former times and which have become rare during the last decades, such as tinea capitis due to Trichophyton schonleinii, still contribute to the spectrum of dermatophytosis in childhood. PMID- 1761792 TI - Gangliosides inhibit the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. AB - T cell growth factors such as interleukin-2 (IL-2) and interleukin-4 (IL-4) act as potent comitogenic factors for purified human T cells in the presence of phorbol myristate acetate (PMA). We investigated the effects of gangliosides on the IL-4-driven or IL-2-driven proliferation of human T cells, using these comitogenic assays. Bovine brain gangliosides inhibited the proliferation of human T cells activated by PMA + IL-4 or PMA + IL-2. These inhibitory effects were dose and time-dependent and were significant at concentrations higher than 50 microM. PMA + IL-2 stimulation was more sensitive to the inhibitory effects of gangliosides (I50 = 77.2 microM) than PMA + IL-4 stimulation (I50 = 105.9 microM). Differential inhibitory effects were also examined among the panel of various gangliosides. GD1b and GT1b showed the most potent inhibitory actions in each assay; the inhibitory effect of GD1a was somewhat less potent than GD1b or GT1b. GM2 and GD3 were only weakly inhibitory, and the inhibitory effect of GM3 was almost negligible. These findings suggest that gangliosides may play an immunomodulatory role by interfering with IL-4 or IL-2-driven proliferation of human T cells. PMID- 1761793 TI - Modulation of epidermal terminal differentiation in patients after long-term topical corticosteroids. AB - The expression of the various markers for terminal epidermal differentiation in atrophic skin of patients after long-term topical corticosteroids (TCS) was studied by electron microscopy, immunofluorescence using antibody to profilaggrin/filaggrin (PF/FG), immunoperoxidase staining using antibody to involucrin, and oil red O stain for neural lipids of the stratum corneum. Thirty nine patients were subdivided into two groups: (A) 19 patients suffering from rebound phenomenon after stopping TCS and (B) 20 patients without rebound phenomenon. Biopsy specimens were taken before ending the use of TCS in both groups. In group A, both the morphological markers (including the different epidermal strata, keratohyalin granules, lamellar granules, and cornified cell envelopes) and the molecular markers (including involucrin, PF/FG, and neutral lipids) of terminal epidermal differentiation were significantly suppressed. On the other hand, the differentiational markers in the atrophic skin of patients without rebound phenomena were only slightly altered. These results suggest that potent TCS not only has antiproliferative actions but also inhibits the differentiation of epidermis, resulting in structural defects in the epidermis, especially the stratum corneum. PMID- 1761794 TI - Sclerotic fibromas of the skin. AB - We report a case of a 34-year-old Japanese woman with a fibrous tumor on the left palm that fulfilled the criteria of sclerotic fibroma of the skin. Immunohistochemically, the tumor cells were positive for vimentin, but negative for S-100 protein and neuron-specific enolase. Ultrastructurally, the cross striations of collagen microfibrils were less prominent. Our case supports the concept that sclerotic fibroma of the skin is a distinctive lesion which may represent a hamartoma of the skin. PMID- 1761795 TI - Lichen nitidus: a histologic and electron microscopic study. AB - A lesion of lichen nitidus in a 53-year-old man was examined by histology and electron microscopy. The histology showed typical features. The electron microscopy revealed primary changes in hydropic degeneration of basal cells which possibly indicated severe edema between the basal keratinocytes and in the subepidermal area. The basal keratinocytes themselves were not particularly altered, except for clustered micro-vacuolar structures in a small portion of the peripheral cytoplasm. In one of the eight blocks observed, the cytoplasmic process of a mast cell was found between the basal keratinocytes, indicating that mast cells may possibly infiltrate the epidermis in lichen nitidus. Scattered mast cells in the dermis were also noted. Thus primary pathologic changes of lichen nitidus may be induced by severe edema, which was accompanied by inflammatory cells including mast cells, in the region of the dermal-epidermal junction. PMID- 1761796 TI - In vitro effects of organophosphorus compounds on calmodulin activity. AB - In vitro effects of organophosphorus compounds (OP), such as malathion (M), methyl parathion (MP) and ethyl parathion (EP), on calmodulin (CaM) activity and its active conformation were studied to understand the mechanism(s) of neurotoxicity, since CaM is known to regulate Ca2+ transport and the enzymes involved in signal transduction and nucleotide metabolism. The biological activity of CaM was assessed as a measure of phosphodiesterase (PDE) stimulation. The effect of OP compounds on the active conformation of CaM was determined by studying the binding of fluorescence probes, namely N-phenyl-1-naphthylamine (NPN), and changes in dansyl-calmodulin fluorescence. Dansylated calmodulin was also used to study the effect of OP compounds on complex formation between CaM and PDE. All three OP compounds inhibited the CaM activity and its active conformation in a concentration-dependent manner. Malathion was less effective in comparison to EP and MP, with IC50 values of 37 microM, 34.5 microM and 32 microM, respectively, for CaM activity. EP and MP significantly altered NPN and dansyl-calmodulin fluorescence (50 microM concentrations of OP compounds), whereas M did not show any significant effect on NPN fluorescence. All these compounds significantly affected complex formation between the dansylated CaM and PDE. These results suggest that OP compounds may be interacting with CaM, altering its active conformation, and thus may be inhibiting its biological activity. PMID- 1761797 TI - Immunotoxicity of tri-n-butyltin oxide (TBTO) and tri-n-butyltin chloride (TBTC) in the rat. AB - In a 1-month feeding trial, pure and commercial tri-n-butyltin oxide (TBTO) and tri-n-butyltin chloride (TBTC) were fed to rats at concentrations of 5 ppm and 25 ppm. At all times, the mean body weight gain and the food consumption was significantly less in rats treated with 25 ppm pure TBTO or pure TBTC as compared to control rats or rats receiving commercial TBTO. Histological examination of the thymus of rats treated for 7 days with TBTO showed atrophy with severe lymphocytic depletion in the cortex. After 28 days of exposure, most of the lesions reversed and the thymus became markedly smaller than in control rats, both in absolute terms and in relation to body weight. Seven days of exposure to TBTO increased liver weight but this change was reversed during a further 3-week exposure. Tin concentrations were the highest in livers and kidneys. Concentrations in the thymus were less than one-fifth of hepatic values. Changes in the rats treated with the commercial TBTO were very similar. Rats treated with TBTC showed lower tin levels and less immunotoxicity as compared to those treated with TBTO. PMID- 1761798 TI - Effects of some organophosphorus compounds on the binding of a radioligand (8 cyclopentyl 1, 3-[3H]dipropylxanthine) to adenosine receptors in ovine cardiac membranes. AB - 8-Cyclopentyl-1,3-[3H] dipropylxanthine [( 3H]CPX) is a potent radioligand that specifically binds to the A1 adenosine receptors. Its high specificity makes it a suitable ligand for the characterization of A1 adenosine receptors in tissues with low receptor densities. We have demonstrated that the organophosphorus compounds soman, tabun and sarin, at relatively high concentrations, all bind to the A1 adenosine receptors in ovine cardiac membranes with Ki values of 36.7, 328 and 175 microM, respectively. The binding of soman to the receptor site was found to be totally reversible. We suggested that these organophosphorus compounds affect the mechanical responses of the heart through interaction with a potassium channel that does not seem to be closely linked to the A1 adenosine receptors. PMID- 1761799 TI - Joint toxic action of binary mixtures of osteolathyrogens at malformation inducing concentrations for Xenopus embryos. AB - The joint action of binary mixtures of the osteolathyrogens semicarbazide (SC), beta-aminopropionitrile (beta APN) and penicillamine (PNC) were determined at malformation-inducing concentrations for Xenopus embryos. Tests were static with renewal every 24 h for the 96-h test period. Simultaneous tests on each individual component of the binary mixtures alone gave baseline malformation data (EC50) for joint action analyses. Toxic unit analysis and isobole diagrams were used to determine the type of joint action for 3:1, 1:1 and 1:3 mixtures of each combination. The joint action was concentration additive (strictly additive) for SC with beta APN and response additive (less-than-additive) for SC with PNC and beta APN with PNC. The joint actions were not changed when only osteolathyrogenic lesions, rather than all types of malformations, were considered. The different specific location and character of PNC lesions, as opposed to those for SC and beta APN, may signify a different type of osteolathyrogenic effect for PNC. The mixture testing approach has potential value in determining compounds that act similarly. PMID- 1761800 TI - Validation of a non-invasive technique to assess immediate or delayed onset of airway hypersensitivity in guinea-pigs. AB - Conscious Hartley guinea-pigs were sensitized with trimellitic anhydride (TMA) or trimeric hexamethylene diisocyanate biuret (Des-N) by repeated intradermal injections or by inhalation exposure. Immediate- and delayed-onset pulmonary reactions were recorded during/after challenges with the hapten or protein conjugate of the hapten, respectively. The positive control was sensitized and challenged with ovalbumin (OA) by inhalation. Homocytotropic antibodies of the IgG1 type were determined to correlate antibody titres and pulmonary responses. Immediate-onset pulmonary reactions were apparent in guinea-pigs sensitized by inhalation of TMA and OA. Animals sensitized intradermally with TMA demonstrated more vigorous immediate-onset reactions than animals sensitized by inhalation. The measurement of breathing parameters demonstrated that the ability to detect immediate-onset airway hyperreactivity was best when the breathing rate and tidal and minute volumes were measured. None of the measurements for delayed-onset reactions presented conclusive results, since sensitized as well as naive guinea pigs demonstrated a delayed increase of breathing frequency. Antigen-specific IgG1 antibodies were several orders of magnitude higher in intradermally sensitized animals compared with animals sensitized by inhalation. Although Des-N sensitized guinea-pigs experienced high IgG1-antibody titres, no response of pulmonary hypersensitivity could be elicited after hapten or conjugate challenge. In summary, it would appear that pulmonary hypersensitivity depends on factors other than IgG1 antibody titres. For the screening of chemicals, the dermal induction and inhalation challenge protocol was revealed to be more sensitive than the inhalation induction and inhalation challenge protocol. PMID- 1761801 TI - Biliary excretion of hexachloro-1,3-butadiene and its relevance to tissue uptake and renal excretion in male rats. AB - Renal, biliary, pulmonary and faecal excretion experiments were carried out with labelled hexachloro-1,3-butadiene [( 14C]HCBD) in male Sprague-Dawley rats, given orally (p.o.) and intravenously (i.v.) in doses of 1 and 100 mg kg-1 as a solution in polyethylene glycol. The radioactivity excreted over 72 h was determined in rats fitted with exteriorized biliary cannulae and in rats whose bile ducts remained fully functional, respectively. In addition, bile duct duodenum cannula-linked rats, of which the donor was given 100 mg kg-1 [14C]HCBD orally and the recipient had also a bile fistula, were examined within 30 h for radioactivity in the excreta, the kidney, the liver and the plasma. In non cannulated rats, fractional urinary excretion decreased when the dosage increased and amounted to 23% and 8.6% after i.v. injection or 18.5% and 8.9% after p.o. administration of 1 and 100 mg kg-1, respectively. Pulmonary excretion of radioactivity was less than 9% and was not affected by the increase in dosage. In bile duct-cannulated rats, fractional urinary excretions were similar irrespective of the dose and the route of administration and amounted to ca. 7.5% of the dose. Decrease in fractional biliary excretion occurred with increase in dosage (88.7% vs 72%) after i.v. injection and (66.8% vs 58%) after gavage. In cannulated rats, faecal excretion was less than 0.5% after i.v. injection and accounted for 3% and 16% of the dose after p.o. administration of 1 and 100 mg kg 1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761802 TI - Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolites p-benzoquinone, muconaldehyde and hydroquinone. AB - Using radio-iron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that p-benzoquinone (BQ) and muconaldehyde (MUC) are potent inhibitors of bone marrow function in female mice. These two benzene metabolites reduced iron uptake at dosages of less than 5-6 mg kg-1. The combination of MUC and hydroquinone (HQ) (100 mg kg-1) was additive, reducing iron incorporation to an extent that was the sum of the effect of each chemical given alone. The combined effect of MUC and BQ was significantly less than additive, demonstrating antagonism in the response. Multiple regression was used to study the contributions of the components of binary mixtures of the benzene metabolites (METAB). Data obtained from standard curves of METAB and their mixtures are separable in regression analysis. Thus, for zero interaction of METAB, the responses would be simply additive, while positive and negative interaction would indicate synergy and antagonism, respectively. T-testing of the data resulted in non-significant values for the mixture MUC + HQ, indicating zero interaction and an additive response. The negative t-values obtained for the mixture MUC + BQ, however, indicate negative interaction or an antagonistic response. Since mutually exclusive agents share the same binding sites and occupation of a site by one agent excludes its occupation by another, they cannot interact in producing the effect; combinations of these agents show zero interaction and are simply additive. This suggests that HQ and MUC are mutually exclusive and share the same binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761803 TI - Toxicology update. PMID- 1761804 TI - Fast thin-layer chromatography systems for fumonisin isolation and identification. PMID- 1761805 TI - Mycotoxins, porphyrias and the decline of the etruscans. PMID- 1761806 TI - Thyroid hormones changes in infants and children with metabolic acidosis. AB - The influence of the acidotic state on the thyroxine (T4) peripheral metabolism was studied in two different forms of metabolic acidosis, ie infantile diarrhea and diabetic ketoacidosis. The serum concentrations of T4, free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), thyrotropin (TSH) and thyroxine-binding globulin (TBG) were measured and compared to healthy control groups. Lower T4 and T3 and higher rT3 serum concentrations were found in both tested groups of patients in relation to the control groups. In infants with severe metabolic acidosis FT4 values were lower than those observed in the control group. In addition, serum TBG levels were lower in diabetic patients as compared to control subjects. Despite the reduced serum T3 and T4 concentrations in both groups of patients, TSH concentrations, were within the normal range. Therefore, we concluded that acidosis caused either by diarrhea (not so far described) or by diabetes mellitus (well documented up to now) affects the thyroid hormones metabolism in a similar way, at least as far as the thyroid hormones blood levels are concerned. PMID- 1761808 TI - Follicular fluid lipoproteins in preovulatory period and their relationship with follicular maturation and progesterone production by human granulosa-luteal cells in vivo and in vitro. AB - Follicular fluid (FF) lipoprotein content was evaluated in an in vitro fertilization/embryo transfer and gamete--intrafallopian--transfer program and correlated to follicular and oocyte maturation. Moreover, the in vitro progesterone response of granulosa-luteal cells from 10 patients to high-density lipoprotein (HDL) and to low-density lipoprotein (LDL) was assessed. Most FFs contained only HDL. Sixteen out of 97 FFs contained also very low levels of LDL and very-low-density lipoprotein (VLDL). The presence of LDL was associated to features of follicle and oocyte hypermaturity. LDL alone induced a much more potent increase of progesterone (P) release by granulosa-luteal cells than HDL alone, and the HDL partially reversed the potent effect of LDL. It is concluded that in late follicular phase HDL maintains P release by granulosa cells at a low rate and prevents a potent stimulation of P production by LDL which might cross the maturating blood-follicle barrier, until increasing passage of LDL in FF decreases the HDL:LDL ratio and the action of LDL becomes prominent. PMID- 1761807 TI - In vivo insulin action in hepatocellular and cholestatic liver cirrhosis. AB - The in vivo dose response curve to insulin were studied, using an euglycemic insulin clamp technique, in 13 cirrhotic patients [8 with "hepatocellular" (HC) (nonalcoholics) and 5 with "cholestatic" (CHOL) cirrhosis] and 12 healthy controls (N). Subjects were studied in the basal state and during infusion of insulin at 3 different rates - 1, 3, 10 mU kg-1 min-1. Insulin responsiveness was similar in N and in HC, but it was 23% greater in CHOL (p less than 0.001). Insulin sensitivity was decreased in cirrhotics as compared with N but this difference was only significant (p less than 0.001) in HC. (ED50:62 + 5, 88 + 13 and 136 + 16 muu ml-1 in N, CHOL and HC respectively). Insulin clearance rate (ICR) was significantly (p less than 0.005) decreased in HC (1060 +/- 80, 996 +/- 95 and 776 +/- 128 ml sq m-1 ml-1 in N, CHOL and HC respectively. Basal hepatic glucose production (BHGP) was 39% lower in HC (p less than 0.005) and 24% lower in CHOL (p less than 0.05) than in N. Erythrocyte cholesterol phospholipid ratio was significantly elevated (p less than 0.001) in both groups of cirrhotic patients but was not correlated to specific metabolic changes described. In summary: i) intervariations in insulin dependent glucose metabolism were described in different cirrhotic groups; ii) basal hepatic glucose production and insulin clearance rate impaired in the different groups of cirrhotics; iii) the role of decreased cholesterol/phospholipid ratio on tissues glucose metabolism in cirrhotic patients should be further studied. PMID- 1761809 TI - Increased mean serum thyrotropin in apparently euthyroid hypercholesterolemic patients: does it mean occult hypothyroidism? AB - Serum thyroid hormones and antithyroid autoantibodies (AAB) were assayed in 87 randomly selected hypercholesterolemic persons compared to 80 controls with normal serum total cholesterol (TC). Of the 87 hypercholesterolemic persons 22 (25%) had positive AAB compared to 5 (6%) controls. Furthermore, 8 of the hypercholesterolemic patients had a serum TSH level above 5 mU/l, i.e. the had subclinical hypothyroidism, not diagnosed before, whereas thyroid function was normal in all normocholesterolemic persons. The new and unexpected finding was that the hypercholesterolemic persons had on average a significantly higher serum TSH than the controls, and this was true even when persons with positive AAB were excluded. There was a significant correlation between TC and serum TSH. It is concluded that hypothyroidism may not be an all-or-none phenomenon, and that many hypercholesterolemic persons with thyroid tests within the conventional normal range may have a slight impairment of their thyroid function. PMID- 1761810 TI - The effect of short-term growth hormone or low-dose oxandrolone treatment in boys with constitutional growth delay. AB - We evaluated the effect of six-month treatment with growth hormone (GH) or low dose oxandrolone in a group of boys with constitutional growth delay (CGD). Sixteen boys were randomly assigned to two treatment groups. Group 1 received GH (0.6 U/kg/week sc 5-6 times/week) and Group 2 received oxandrolone (0.07 mg/kg po). The boys of the two groups were closely matched for age (13.7 +/- 0.5 and 12.8 +/- 0.4 years) (mean +/- SE), chronologic age/bone age ratio (1.15 +/- 0.04 and 1.16 +/- 0.02), height standard deviation score (SDS; -2.7 +/- 0.4 and -2.5 +/- 0.3) and pretreatment height velocity (HV) (3.7 +/- 0.8 and 4.0 +/- 0.4 cm/year). Other known causes of short stature were excluded in all subjects, and none had taken long-term medication prior to the study. After 6 months of treatment HV increased to 7.5 +/- 0.4 and to 8.1 +/- 0.5 cm/year in group 1 and 2, respectively. Plasma IGF-I concentrations rose significantly after treatment in both groups. Predicted adult height was not significantly affected by either GH or oxandrolone treatment. We conclude that a short-term course of low-dose oxandrolone is as effective as GH to accelerate growth in boys with CGD. Low-dose oxandrolone represents an effective, cheap, and convenient therapeutic approach in boys with CGD. PMID- 1761811 TI - Glucose tolerance and insulin release in adolescent female. AB - The increase in insulin requirement at the onset of adolescence is compensated by an increase of insulin secretion. This metabolic pattern persists during adolescence but is no longer present in adults. It is supposed to depend on a decrease of insulin sensitivity of uncertain origin. We compared the metabolic pattern of late adolescent girls (13-16 year old) with young women (21-30 year old) with similar body mass indexes, testing subjects with iv glucose tolerance test (IVGTT) (glucose 0.33 g/kg) and arginine test (ATT) (arginine 30 g in 30 min). In late adolescent vs adult women we observed: i) IVTT: similar k of glucose tolerance and higher insulin and C-peptide responses; ii) ATT: unmodified plasma glucose, insulin and glucagon values, higher GH plasma levels; iii) in adolescent girls GH and CPR incremental areas significantly correlated (r = 0.755, p less than 0.05). These data show that: i) the adolescent pattern of glucose metabolism persists after completion of sexual development and, ii) there is a positive correlation between GH response to arginine and beta-cell response to glucose. So GH should play a role in the impairment of glucose metabolism during adolescence. PMID- 1761812 TI - Increased rat femur osteocalcin mRNA concentrations following in vivo administration of thyroid hormone. AB - Thyroid hormone has a direct resorptive effect on bone. Thyroid hormone therapy in doses that suppress pituitary TSH production result in a reduction in bone density. Osteocalcin is a bone matrix protein. Serum levels are a sensitive marker for bone turnover and are increased in hyperthyroid patients. In order to establish an animal model to study the effects of thyroid hormone on bone turnover, we measured rat femur osteocalcin mRNA following in vivo administration of thyroid hormone. Young CD rats weighing 60-90 g were given daily ip injections of T3, T4, or saline (control) for 12 days. Blood was obtained for radioimmunoassays, and RNA was extracted from femurs and analyzed by Northern blot using a 60-mer synthetic oligonucleotide probe corresponding to bases 360 420 of rat osteocalcin mRNA, labeled with [32P] ATP by 5'-end-labeling. Serum TSH concentrations were suppressed to subnormal levels by the lowest doses of T3 and T4, and to undetectable levels by the higher doses. Increases in serum T3 and T4 concentrations were proportional to the dose of each administered hormone. T3, 5 and 10 micrograms/100 g body weight, resulted in a 43% and 62% increase in osteocalcin mRNA, respectively. T4, 5, 10, and 20 micrograms/100 g body weight, resulted in a 35%, 47%, and 135% increase in osteocalcin mRNA, respectively. These data demonstrate that in vivo administration of either T4 or T3 to young rats results in a significant dose-dependent increase in femur osteocalcin mRNA concentrations. PMID- 1761813 TI - Riedel's thyroiditis associated with Hashimoto's thyroiditis, hypoparathyroidism, and retroperitoneal fibrosis. AB - A patient with Riedel's struma (invasive fibrous thyroiditis) with hypothyroidism, hypoparathyroidism, and retroperitoneal fibrosis is reported. This disorder appeared to emanate from Hashimoto's thyroiditis in this case. The possible relationship of the two entities is discussed. PMID- 1761814 TI - Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism. AB - High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761815 TI - Thyroid function in systemic sclerosis. PMID- 1761816 TI - Hypertension in elders. Clinical diagnosis and treatment considerations. AB - Isolated systolic hypertension (ISH) accounts for more than 50% of all hypertension in persons over age 65 and is linked to increased morbidity and mortality. The various antihypertensive medications have been shown to be effective in reducing ISH. However, the efficacy of such treatment in reducing morbidity and mortality has been demonstrated in only one study to date and only on a selected population. The care provider for an elderly person with ISH must therefore weigh the risks of ISH against the risks of treatment of side effects and quality of life. Ultimately, the treatment of ISH in those over age 65 must be carefully planned on an individual basis. PMID- 1761817 TI - Reminiscence behavior: an empirical exploration. AB - Engagement in the process of reminiscing involves the use of detail and depth, easy access to memories, and requests for feedback from the listener. Engagement in reminiscing may be stable during old age or may follow a developmental course. Avoidance behaviors, defined as switching to non-reminiscing topics or giving neutral/informative responses, were prevalent among non-engaged reminiscers. Understanding what a person chooses to avoid reminiscing about is as important as what a person chooses to reminisce about. Diversity refers to the degree to which engaged reminiscers varied the events they reminisced about. Diversity of verbalizing both validating and lamenting reminiscences may related to the specific usefulness of reminiscence as an intervention. Two distinct reminiscence interventions are currently being used: life review and psychosocial reminiscing. Findings regarding engagement and diversity of reminiscing suggest more effort is needed in prescribing the appropriate reminiscing intervention. PMID- 1761818 TI - Mental dysfunction: a clinical pilot project in the elderly. AB - In recognizing that there will be an increase in the number of individuals with dementing illnesses well into the next century, the authors show how one institution is coping with this problem today. The authors outline an innovative approach to admission and discharge planning and monitoring of patients with irreversible dementias and behavioral problems. Nurses and other team members need a mechanism (ie, a flow chart) to monitor behavior and plot progress within an individualized program designed to meet the needs of dementia patients. PMID- 1761819 TI - Assessing toileting skills and habits in an adult day care center. AB - In a structured assessment of mobility and toileting skills, all the continent clients but only 46.2% of incontinent clients were able to toilet themselves, even with verbal and physical guidance. Unobtrusive observation of toileting habits indicated that incontinent clients used the toilet less often than continent clients and used more staff assistance to do so. On mental status examination, incontinent clients scored significantly lower than continent clients. Incontinence in this population is a multidimensional disorder in which physical disability is a predominant factor. PMID- 1761820 TI - The Advisory Panel on Alzheimer's Disease second annual report: what's in it for gerontological nurses? PMID- 1761821 TI - Sharing the legacy. Hospice care principles for terminally ill elders. AB - Hospice care is usually chosen as the preferred mode of care when the patient and family judge that the burdens of aggressive treatment are greater than the benefits that can be expected. Hospice treatment is directed at controlling pain, relieving other symptoms, and focusing on the special needs of the hospice patient and the patient's family. The objective of hospice care is to prevent breakthrough pain while maintaining an acceptable level of consciousness. Family teaching in hospices is centered around appropriate responses to physical and emotional/spiritual/mental signs and symptoms of approaching death. PMID- 1761822 TI - Agitated behavior in the cognitively impaired elderly. AB - The study of agitation is of interest to caregivers because of potential nursing interventions that could be implemented to prevent or alleviate these behaviors. To ensure an effective plan of care for agitated patients, it is essential that the assessment be based on an objective measurement of the observed agitated behavior. Reliability and validity of the three instruments used to measure agitation were supported; however, none were considered an ideal tool for use with this population because frequently observed behaviors fell into the nonspecific "other" category. Agitated behaviors were highly variable among the subjects in this study; thus, no predictable pattern of occurrence could be established. PMID- 1761823 TI - Controlling large malpractice claims: the unexpected impact of damage caps. AB - Indiana's comprehensive malpractice reforms, inaugurated in 1975, include a cap on damages, a mandated medical review before trial, and a state insurance fund to pay claims equal to or greater than $100,000. We have found that the amount of compensation going to claimants with such large malpractice claims in Indiana is, on average, substantially higher than in Michigan and Ohio. Indiana's mean claim severity between 1977 and 1988 was $404,832, while the means for Michigan and Ohio were $290,022 and $303,220, respectively, with the difference between these three means being highly significant. Although data on claim and claimant characteristics reveal considerable interstate variation, the results of regression analyses show that Indiana claim payment amounts are higher than Michigan or Ohio payments, independent of the effect of factors such as sex, age, severity of injury, allegations of negligence, and year of settlement. PMID- 1761824 TI - Lessons for tort reform from Indiana. PMID- 1761825 TI - Sources of countervailing power in medicine. AB - In recent years a substantial literature has emerged on the alleged deprofessionalization and proletarianization of physicians. The contention is that corporatization is transforming the practice of medicine, divesting physicians of control over many features of their work, consistent with the needs of advanced capitalism. I examine the hypothesis skeptically, differentiating between the cultural role of medicine, the political and social legitimacy of medical concepts, and the personal autonomy of the individual physician. I suggest that while physicians are less autonomous than they used to be, the constraints imposed on them fall within a medical paradigm. From a cultural or social perspective, medicine is more central to the economy and more powerful than ever before. As its centrality and importance increase, there is more at stake, and interests compete more aggressively. I conclude that there is little evidence in support of the hypothesis. PMID- 1761826 TI - Professionalism as a countervailing power. PMID- 1761827 TI - Administrative and policy issues in reimbursement for nursing home capital investment. AB - The way in which states reimburse for nursing home capital costs can create incentives for nursing home owners to use the home primarily as a vehicle for real estate speculation, with potentially adverse consequences for patient care. In order to help promote and control the stability, adequacy, and quality of capital investment in long-term care, an increasing number of states are using a fair-rental approach for calculating capital reimbursement. In this article we compare the fair-rental approach with traditional cost-based capital reimbursement in terms of administration and policy. We discuss issues of concern to the state (cost and reimbursement design options) and the investor (after-tax cash flows, rate of return, etc.). Our analysis suggests that fair-rental systems may be superior to traditional cost-based reimbursement in promoting and controlling industry stability, while at the same time providing an adequate return to investors, without incurring long-term increases in the costs of administering programs. PMID- 1761828 TI - Further issues in small area variations analysis. AB - In this article, I examine Wennberg's "practice style" hypothesis and the literature on variations among small areas. According to Wennberg, geographic variations in rates of per capita use for many clinical procedures arise mainly from differences over what constitutes appropriate care. I show, however, that the role of practice style in explaining variations among areas has not been clearly demonstrated. I also argue that the practice style hypothesis can neither be established nor refuted by the methods traditionally used to study small areas and, moreover, that inferences about practice style variations cannot be drawn from differences among areas in their rates of use. I thus conclude that more research at the micro level in the practice patterns of the individual physician is needed before major health care initiatives based on small area methodology are undertaken. PMID- 1761829 TI - Insuring women's health. PMID- 1761830 TI - Themes in medical sociology. PMID- 1761831 TI - Disease or illness: alcoholism as social metaphor. Review essay. PMID- 1761832 TI - Abdominal migraine: does it exist? AB - Abdominal migraine is well recognised in children, but in spite of anecdotal reports migraine is not well established as a cause of abdominal pain in adults. Functional abdominal pain is usually classified as either irritable bowel syndrome or nonulcer dyspepsia, but some patients have intermittent abdominal pain associated with headache or other migraine accompaniments and, in these, a diagnosis of abdominal migraine should be considered. It is possible that some patients with functional abdominal pain have migraine presenting with few or even no migraine accompaniments. There is no nonclinical objective standard for diagnosing migraine, and research in this area is therefore very difficult. Nevertheless, some patients with functional abdominal pain may respond to antimigraine medication and, if their symptoms are suggestive, a trial of therapy may be desirable. PMID- 1761833 TI - Structural analysis in medicine--hiatal hernia, heartburn, Hercules, and the Hydra. AB - In this issue, we report that esophagitis is associated with the presence of a hiatal hernia, but not with smoking or the pressure of the lower esophageal sphincter. This editorial argues that our sampling and statistical methods were appropriate. We discuss how these methods can be employed in future studies. PMID- 1761834 TI - The role of educational videos in gastroenterology. AB - The potential role for video tape education in gastroenterology is discussed. The need for material to inform patients about their diagnoses is widely acknowledged and educators need to take advantage of modern techniques. Studies in general practice, diabetes care, and asthma care have found that videos have significant benefits when compared with conventional techniques. There are few such video tapes available to gastroenterologists. It has been shown that patients are keen to accept educational material in this form provided it is shown at a suitable time and in a suitable venue. PMID- 1761835 TI - Significant role of aspirin use in patients with esophagitis. AB - This study determines objectively the extent of nonsteroidal anti-inflammatory drug (NSAID) use in upper gastrointestinal (GI) mucosal acid-peptic diseases by supplementing the conventional interview with two tests of current aspirin (ASA) use--high-performance liquid chromatography (HPLC) for the presence of salicylates in serum and platelet cyclooxygenase activity, which detects ASA use within 5 days of testing. Of 186 consecutive patients undergoing upper endoscopy, 62% of 55 patients with esophagitis had evidence of current NSAID use, vs. 26% of 42 control patients with normal endoscopy (p less than 0.001), 12% of 17 patients with recently healed peptic ulcer (p less than 0.001), and 36% of 25 patients who had an active peptic ulcer (p less than 0.05), five of whom had concomitant esophagitis. Another 52 patients were ineligible for this analysis. Testing for platelet cyclooxygenase activity uncovered 26% more ASA users than history alone. In considering age, sex, smoking and drinking habits, arthritis, and ASA use by logistic regression, ASA use was the only factor contributing to esophagitis; ASA could not be further associated with severity, stricture or symptoms, however. In these patients, 95% of NSAID use was chronic, and 84% of that was ASA. These data show a previously unreported, strong association of ASA use with esophagitis, which suggests that ASA may be a significant factor in the resistance of esophagitis to current therapies as well as the frequently rapid relapse after therapy is withdrawn. PMID- 1761836 TI - The importance of hiatal hernia in reflux esophagitis compared with lower esophageal sphincter pressure or smoking. AB - The characteristics of gastroesophageal reflux disease have not been adequately defined. To determine the influence on the esophageal mucosa of hiatal hernia, lower esophageal sphincter pressure, acid reflux, and cigarettes and alcohol, we studied the reflux parameters, smoking habits, and alcohol consumption of 184 healthy, ambulatory outpatients who received endoscopy as the initial diagnostic procedure for workup of gastroesophageal reflux. Patients received endoscopic and histologic evaluations of the esophageal mucosa, prolonged ambulatory esophageal pH monitoring, and esophageal manometric determinations. Structural analysis was used to test the plausibility of various clinical theories concerning the most important factors contributing to the development of esophagitis. Statistical analyses revealed the following: (a) the lower esophageal sphincter pressure, acid contact time, and frequency of reflux episodes were highly associated with the presence of a hiatal hernia (p less than 0.003 for all parameters); (b) individuals with esophagitis had 16.5 times as many hiatal hernias as found in normal, healthy people; (c) cigarette smoking was not correlated with esophagitis but was significantly associated with increased lower esophageal sphincter pressure (r = 0.18; p less than 0.03); and (d) smoking was also not associated with increased acid contact time or increased frequency of reflux episodes. We conclude that (a) the presence of a hiatal hernia, not the pressure of the lower esophageal sphincter, is the most important predictor of reflux frequency, acid contact time, and esophagitis; (b) a decreased lower esophageal sphincter pressure, as suggested by structural analysis, is unlikely to be the cause of increased reflux episodes or esophagitis; and (c) if smoking and lower esophageal sphincter pressure are factors in the development of esophagitis, they damage the esophageal mucosa by mechanisms other than increased frequency of reflux episodes or increased acid contact time. PMID- 1761837 TI - HIV-1 gp41 antigen demonstration in esophageal ulcers with acquired immunodeficiency syndrome. AB - Esophageal ulcers associated with acquired immunodeficiency syndrome (AIDS) may be chronic, debilitating, and resistant to antifungal or antiviral therapy. The therapeutic management of these lesions remains controversial due to the difficulty in identifying pathogenic agent(s). We review previously published cases and describe three AIDS patients with esophageal ulcers that stained by immunoperoxidase techniques for human immunodeficiency virus (HIV)-1 surface glyloprotein (gp41). All three showed symptomatic resolution and healing of their ulcers with corticosteroid therapy. We believe this documentation of HIV-1 gp41 antigen within mononuclear cells of esophageal ulcers in AIDS supports a role of the HIV-1 virus in the pathophysiology of idiopathic esophageal ulcers in patients with AIDS. These cases further support a role for corticosteroid therapy in the treatment of esophageal ulcers resistant to antifungal and antiviral therapy in patients with AIDS. PMID- 1761838 TI - Arterial oxygen saturation, blood pressure, and pulse rate during upper gastrointestinal endoscopy--influence of sedation and age. AB - We studied the effect of sedation by I.V. meperidine on blood pressure, pulse rate, and arterial oxygen saturation during upper gastrointestinal endoscopy. Meperidine increased the tolerance of the patients and attenuated the endoscopy induced rise in blood pressure and pulse rate. Arterial oxygen saturation was transiently depressed in the first few minutes of the endoscopic procedure even without sedation, and meperidine administration did not aggravate this oxygen desaturation. Therefore, meperidine may be a favorable sedative for upper gastrointestinal endoscopy because its treatment increases the tolerance of patients and decreases cardiac oxygen demand without decreasing arterial oxygen saturation. PMID- 1761839 TI - Anorectal manometry and defecography in the diagnosis of fecal incontinence. AB - We carried out anorectal manometry and defecography prospectively in 43 consecutive patients with fecal incontinence. A subgroup of 17 patients with severe incontinence was identified radiologically by a short and incompletely closed anal canal. In these patients, the anal resting pressure was significantly lower than in the rest of the group (34.9 +/- 11.4 mm Hg versus 60.0 +/- 25.7 mm Hg, respectively; p less than 0.01). The anorectal angle did not change in 24 patients during squeezing, indicating a dysfunction of the puborectalis muscle. Manometric data did not differ between this subgroup and patients with a more acute anorectal angle during voluntary sphincter contraction. This indicates that the anal pressures recorded manometrically do not reflect the function of a muscular component that is important in the maintenance of fecal continence. We conclude that anorectal manometry and defecography are complementary diagnostic tools in the investigation of patients with fecal incontinence. PMID- 1761840 TI - Acute pancreatitis associated with anomalous union of the pancreaticobiliary ductal system. AB - Between 1978 and 1989, 13 of 48 patients with anomalous union of the pancreaticobiliary ductal system (AUPBD) were diagnosed as having acute pancreatitis. We have studied the clinical, radiologic, and surgical features of these 13 patients. A transient rise in the intraductal pressure of the pancreatic duct during an episode of abdominal pain is responsible for pancreatitis in patients with AUPBD. This rise in the intraductal pressure must be due to bile reflux into the pancreatic duct when an abnormally long common channel is blocked by cholelithiasis, protein plug, or dysfunction of the sphincter of Oddi. The pancreatitis resolves when the common channel obstruction is removed, and bile and pancreatic juice flow easily into the duodenum. We believe that this phenomenon is responsible for acute relapsing pancreatitis. It is our belief that the pancreas appears almost normal during symptom-free intervals. PMID- 1761841 TI - Peptic-ulcer-induced aortoenteric fistula. Report of a case and review of the literature. AB - A 71-year-old woman with a remote history of esophagogastric resection for malignancy developed abdominal pain, nausea and vomiting. She died of shock 15 days after admission, during which time clinical investigation failed to reveal recurrent tumor or an ulcer. The autopsy revealed massive exsanguination secondary to a peptic-ulcer-induced aortoenteric fistula (AEF). The ulcer involved the third portion of the duodenum, was chronic, and complicated by growth of fungus. We review the literature on peptic-ulcer-related AEF. PMID- 1761842 TI - Methamphetamine-induced ischemic colitis. AB - A 50-year-old woman with acute onset of right lower quadrant pain and hematochezia proved to have segmental ischemic colitis associated with methamphetamine abuse. The diagnosis was established by colonoscopy with biopsy, and abdominal angiography revealed no thrombosis, vasculitis, or vasospasm. The condition resolved within 10 days. Since methamphetamine abuse is increasing, physicians should be aware of its potential to produce intestinal ischemia. PMID- 1761843 TI - Valproic-acid-induced pancreatitis. Case report and review of the literature. AB - We report a case of pancreatitis with fatal liver failure, in a 21-year-old, mentally retarded patient, taking valproic acid (VPA) therapy, together with a review of the literature of this rare side effect. Until March 1991, only 24 cases of isolated pancreatitis and six cases (including ours) of pancreatitis with hepatic failure under VPA treatment have been published. Most of the patients were less than 20 years old, and injury to the pancreas developed during the first year of therapy in 72% of the patients, approaching a mortality of 21%. Pancreatitis associated with liver failure has a poor prognosis mainly because of the VPA hepatotoxicity. It seems that the pancreatic side effects fluctuate between two extremes: asymptomatic hyperamylasemia and fatal pancreatitis. PMID- 1761844 TI - Endogenous septic endophthalmitis in severe acute hepatitis with septicemia. AB - Endogenous bacterial endophthalmitis occurred in a hepatitis B virus carrier during an episode of severe hepatitis complicated by anaerobic septicemia and possible spontaneous bacterial peritonitis. This may well represent another complication of severe hepatitis with anaerobic bacteremia. PMID- 1761845 TI - Gallbladder abnormalities in acute viral hepatitis: a prospective ultrasound evaluation. AB - We carried out a prospective case controlled study to evaluate the temporal sequence of sonographic abnormalities in acute viral hepatitis (AVH) and their resolution patterns. Correlations were established between the sonographic abnormalities and the clinical and biochemical profiles. Fifty-six patients within 2 weeks of onset of illness (37 within 1 week and 19 between 1 and 2 weeks) underwent real-time ultrasound at weekly intervals until clinical and biochemical resolution. Abnormal sonographic patterns were found in 55 of 56 (98.2%) patients. The wall thickness was abnormal (6.1 +/- 4.3 mm) in 55 (98.2%) cases, luminal abnormalities observed in 33 (58.9%) cases, and alterations in volume in 14 (25%) cases. Complete resolution took place in 53 (96.4%) cases by 12 weeks. A wall thickness of greater than 7 mm and abnormal luminal contents were more frequent in patients studied within 1 week of illness than later (p less than 0.05). No other correlations could be established between the different sonographic patterns and the clinical and biochemical profiles at any stage of the illness. We conclude that sonographic abnormalities are common in patients with AVH, with resolution as the rule with clinical recovery. PMID- 1761846 TI - The role of intrahepatic portal venous stenosis in the formation and progression of hepatolithiasis: morphological evaluation of autopsy and surgical series. AB - Recently, it has been suspected in animal models that a decrease in portal blood flow plays a role in the formation and progression of hepatolithiasis. To find whether this hypothesis is applicable to humans, we examined histologically the intrahepatic portal venous and arterial systems in normal livers (n = 13), extrahepatic biliary obstruction (n = 18), intrahepatic biliary sludge and microcalculi (n = 18, most of which were associated with biliary obstruction and might represent pathogenesis of an early developmental stage of hepatolithiasis), and fully developed hepatolithiasis composed of calcium bilirubinate stones (n = 30). A scoring method was employed to quantify portal stenosis, portal phlebosclerosis, arterial stenosis, and parenchymal atrophy. We found that these vascular changes were significantly more severe in hepatolithiasis than in biliary sludge and microcalculi, or in extrahepatic biliary obstruction. There were no significant differences in the vascular changes except for arterial stenosis between the latter two. There is a positive correlation between vascular stenosis and parenchymal atrophy. These findings suggest that portal venous stenosis deteriorates during the progression of hepatolithiasis. We could not find direct evidence that portal venous stenosis is an initial lesion followed by the formation of hepatolithiasis. The vascular changes may be caused by an inflammatory extension of cholangitis and may deteriorate, causing parenchymal atrophy during the progression of hepatolithiasis. PMID- 1761847 TI - Acute pancreatitis induced by mesalazine. PMID- 1761848 TI - Ectopic pancreas cyst in the mesocolon. PMID- 1761849 TI - A case seeking an entity. PMID- 1761850 TI - Wide QRS tachycardia. AB - Wide QRS tachycardia is a diagnostic challenge when confronted on a 12-lead electrocardiogram. The differential diagnosis includes: ventricular tachycardia; supraventricular tachycardia with aberration; and Wolff-Parkinson-White syndrome. Confronted with a wide QRS tachycardia, one must determine whether the origin is ventricular or supraventricular because the therapy will differ. The electrocardiographic findings of capture beats, fusion beats and atrioventricular dissociation are highly specific for ventricular tachycardia but not very sensitive. After careful assessment of the 12-lead electrocardiogram following selected diagnostic features, the correct diagnosis of the cause of wide QRS tachycardia can be made in about 90 percent of patients. This article contains a brief discussion of the diagnostic features of wide QRS tachycardia. PMID- 1761851 TI - Thoracolumbar spinal fractures--concepts of treatment. AB - The treatment of thoracolumbar spinal fractures has evolved significantly in the last 50 years. Clear classification systems now allow physicians to predict which fracture patterns will require surgery and which may be adequately treated non operatively. These indications, as well as a brief overview of thoracolumbar spinal fracture care, are presented. PMID- 1761852 TI - Young woman with large chest mass. PMID- 1761853 TI - Carpal tunnel syndrome. PMID- 1761854 TI - Physicians' attitudes toward hospital ethics committees. PMID- 1761855 TI - Doctors, families and difficult decisions: the implications of the Lawrance case. PMID- 1761856 TI - Hepatitis C. PMID- 1761857 TI - Wittgenstein on Kohler and Gestalt psychology: a critique. AB - Wittgenstein's objections to Kohler and gestalt psychology are critically examined. Principal features of Kohler's Gestalt Psychology are discussed that are relevant to Wittgenstein's views. They include Kohler's concepts of "subjective" and "objective" experiences, "sensory organization," and "empiristic theory." Wittgenstein's objections, which focus on the concept of sensory organization, are examined. Wittgenstein employs the term "aspect," which is derived from the findings of gestalt psychology, as a replacement for Kohler's term "sensory organization." After tracing his uses of aspect, it is shown that aspect is a superordinate entity distinct from 'sensory content' (colors and shapes). This dualism of aspect and sensory content is of the same kind that prevailed in the empiristic theory of visual perception. Wittgenstein's adherence to the empiristic theory is discussed. Finally, the difference between Wittgenstein's aspect and Kohler's sensory organization is examined. PMID- 1761858 TI - Psychiatry, psychoanalysis, and politics during the First World War. AB - This article compares the therapeutic power used by psychiatrists and psychoanalysts serving in the German and Austro-Hungarian armies during World War I, and the ways in which their therapeutic techniques were related to governmental and military authority. When treating "shell shocked" soldiers, army psychiatrists were guided by nationalist commitment rather than concern for their patients. Whatever theoretical approach they took, they defined their therapeutic task as administrative intervention aimed to increase the docility of soldiers to the state and its military purposes. But violent means of coercion, designed to force neurotic soldiers back into duty, remained inefficient. Drawing from an alternative body of knowledge, army physicians influenced by Freud's writings, or trained in psychoanalysis, applied cathartic methods to treat the Central Powers' soldiers. Their approach was not only more humane, but also proved to be therapeutically more efficient. PMID- 1761859 TI - Psychoanalytic ethics: Edoardo Weiss, Freud, and Mussolini. AB - This paper examines Edoardo Weiss's correspondence with S. Freud regarding Concetta Forzano's analysis and Forzano's efforts to intercede with Mussolini on Freud's behalf after the Nazis invaded Austria in 1938. Freud's reliance on Mussolini can be explained by traditional Viennese attitudes toward Italy, the Duce's protectiveness about Austrian independence, and the relatively benign attitude of the Fascist regime towards Jews. PMID- 1761860 TI - [Continent urinary diversions]. AB - A series of 200 continent Benchekroun pouchs are presented. This original technique, with a hydraulic continence valve, provided a 91.5% continent rate. A review of the literature puts this technique into perspective. PMID- 1761861 TI - [What may be expected from endorectal ultrasonography and magnetic resonance imaging in the assessment of local extension of cancer of the prostate?]. AB - 30 patients presenting with a clinical stage A or B cancer underwent TRUS and MRI with a body coil prior to radical prostatectomy. Imaging and pathology were correlated to assess the limits of TRUS and MRI in pre-operative staging of prostatic carcinoma. Results showed that TRUS and MRI had a sensitivity of 42 and 66% and a specificity of 89 and 94% respectively, for the diagnosis of macroscopic capsular effraction. Seminal vesicle invasion was diagnosed by TRUS with a sensitivity of 16% and a specificity of 81%. With MRI, the sensitivity and the specificity were 85 and 94% if only gross infiltration was considered. Sensitivity dropped to 45% if microscopic invasion was included. We conclude that: (1) postero-lateral venous plexus are more easily delineated by MRI, permitting a more accurate diagnosis of capsular penetration. (2) Seminal vesicle invasion cannot be diagnosed by TRUS as the echostructure of the cancer and the caudal junction of the seminal vesicles and vas deferens are similar. (3) A normal caudal junction on TRUS or a normal bilateral hypersignal of the seminal vesicles on MRI are associated with seminal vesicle invasion in less than 5% of cases. (4) A normal caudal junction on TRUS eliminates false positive cases of MRI related to non tumoral hyposignals of the seminal vesicles. PMID- 1761862 TI - [Fistulas and ureteral strictures after kidney transplantation. Diagnosis and treatment]. AB - We report our experience of 4 urine fistulas and 4 ureteral strictures after renal transplantation. Percutaneous nephrostomy was performed on all patients. The diagnosis was established by antegrade pyelography. Nephrectomy was performed on 2 patients because of failure of drainage and formation of an infected urine collection due to an extended ureteral necrosis. Abstention was elected in one case as renal function did not improve due to associated chronic rejection. In 5 cases, renal function quickly improved with drainage: 2 were operated on immediately, and one after failure of endo-urological treatment of a urine fistula. Antegrade dilatation has been used successfully in one stenosis. In the last case, a double pigtail stent allowed a urine fistula to close. Percutaneous nephrostomy seems to be best method of drainage when ureteral obstruction or fistula is suspected in renal transplant patients, and permits diagnosis by antegrade pyelography. Percutaneous management may be a satisfactory way of treatment for limited stenosis or fistulas. PMID- 1761863 TI - [Urethral lesion associated with perineal tissue defect: immediate combined repair with a musculocutaneous flap from the m. gracilis]. AB - Facing urethro-perineal lesions with large soft tissue defects, the surgeon has to set himself a fourfold target. First, the urethral lesion has to be repaired, and second it needs immediate protection. Third, the tissue defect needs to be filled up, and forth the skin should be closed. A double team surgery, combining the urethral repair and its immediate covering by a gracilis musculo-cutaneous flap, has given functional and morphological results. The highly vascularized muscular portion of the flap prevents local infection and warrants good wound healing in an ischemic region. Its bulk may fill the perineal defect and protect a delicate urethroplasty. With the growing collaboration between urologic and plastic surgeons, this technique will probably find wider indications, possibly when dealing with important perineal trauma. PMID- 1761865 TI - [Tumors of the bladder in patients under 40 years of age]. AB - It is often stated that younger patients have a better prognosis than their older counterparts. From the records of 17 men and 2 women, aged 40 years or less it appears that bladder carcinoma in patients 30 years-old or less have a favorable prognosis. Disease occurring at age 30 to 40 has a much worse prognosis and is no different from that affecting the older age groups. PMID- 1761864 TI - [Resection of pyelo-ureteral junction without external urinary drainage for primary ureteral stenosis]. AB - During a 3-year period 30 consecutive patients (20 women and 10 men) with primary ureteropelvic junction obstruction underwent open dismembered pyeloplasty associated with the placement of an indwelling double pigtail stent via antegrade approach. Renal stones were removed in 8 cases, multiple nephrotomies being necessary in 2 patients. 2 men had temporary urinary leakage. Mean hospitalization time after surgical procedure was 9,8 days, but last 18 patients were discharged after only 7,3 days, Stents were removed 4 to 5 weeks after operation. With 1 to 4 years post-operative follow-up, successful treatment with relief of obstruction was achieved in all 38 patients without secondary stricture. Open pyeloplasty with double pigtail stenting appears to be a safe and successful procedure for the treatment of primary ureteropelvic junction obstruction in adults. Comparison with percutaneous endopyelotomy in terms of morbidity, duration of hospitalization and success rate appears to be in favor of open procedure, although secondary stricture may require endourological procedure. PMID- 1761866 TI - [Value of a clinical test for the assessment of bladder and sphincter function in the management of urinary disorders in the aged]. AB - The authors report about the merits of a clinical test for the evaluation of bladder and sphincter function in the analysis of urinary disorders in the aged. This simple and inexpensive bedside test has been carried out in 175 subjects whose mean age was 81.2 years, and the majority of whom (66.2%) presented with urinary incontinence; 80% of the patients came from longterm-care geriatric departments. The most frequent mechanism is bladder instability (41% of all patients). The cystomanometric data obtained in 80 subjects were analysed and retrospectively compared to the test data: they showed good correlation for the study of vesical stability. From the viewpoint of general health care, this test is a real diagnostic tool for the practitioners, in particular in geriatric departments without further specialised exploration commodities. PMID- 1761867 TI - [Epidermoid tumors of the penis. Clinical experience and review of the literature]. PMID- 1761868 TI - [Simplified technique for uretero-ileal anastomosis in ureteral diversion using an ileal conduit]. AB - The authors report a simplified technique for uretero-ileal anastomosis. It avoids the opening of the ileal segment, avoids doing a direct anastomosis, leaves a 2 cm ureteric segment floating free inside the bowel lumen as a "flap valve". An ileal sleeve is made around the ureter, using the ileal wall, to prevent ileo-ureteral reflux. PMID- 1761869 TI - [A rare complication of extracorporeal shock wave lithotripsy: rupture of the kidney. Apropos of a case]. AB - The authors report one case of renal rupture occurring during an extracorporeal shock wave lithotripsy (ESWL). The patient presented with a bilateral urolithiasis and ESWL, was performed on a large stone (3 cm x 3.5 cm) located in the lower calyx of the right kidney. Ultrasound and CT Scan were used to diagnose the renal rupture and a partial nephrectomy was performed. PMID- 1761870 TI - [Epididymitis in infants. Apropos of a case and review of the literature]. AB - Epididymitis is a rare disease in infants, and its symptoms are the same as those of torsion of the spermatic cord or of its adnexa. Its diagnosis is often surgical, and should lead to suspecting possible associated urogenital abnormalities, requiring appropriate urological investigations. PMID- 1761871 TI - [Hydatid cyst of the right kidney invading into the duodenum. Apropos of a case]. AB - The authors report about one case of hydatid cyst of the right kidney with a fissure opening into the duodenum. They emphasize the exceptional character of this complication, as well as the importance of imaging for its diagnosis. PMID- 1761872 TI - [Retroperitoneal fibrosis in a patient treated with bromocriptine for a prolactinoma]. AB - We present one case of retroperitoneal fibrosis occurring in a patient presenting with a prolactinoma identified five years previously and treated with bromocriptine since then. Bromocriptine, an ergot derivative with a dopaminergic action, seems to be the cause of the fibrosis in this patient. PMID- 1761873 TI - [Oncocytoma of the kidney. Apropos of a case and review of the literature]. AB - Renal oncocytoma is an unusual benign tumor, occasionally suspected on preoperative clinicoradiological features. Its diagnosis is histopathological. We report such a case, in which gross appearance showed renal cell carcinoma signs, but oncocytoma was suspected prior to surgery, confirmed by histopathology including electron microscopy. PMID- 1761874 TI - DNA analysis of oral leukoplakia by flow cytometry. AB - DNA ploidy of 19 oral leukoplakias with and without epithelial dysplasia was investigated and the results were compared with 11 normal gingival biopsies, 14 oral benign tumours and 50 oral squamous cell carcinomas. The results suggest a possible relationship between DNA aneuploidy and oral leukoplakias or squamous cell carcinomas, as 32% of the oral leukoplakias and 48% of the oral squamous cell carcinomas were aneuploid although all the normal gingival biopsies and the benign oral tumours examined were diploid. No significant relationship was observed, however, between DNA ploidy and epithelial dysplasia in the leukoplakias. PMID- 1761875 TI - Efficacy of oral midazolam prior to intravenous sedation for the removal of third molars. AB - The combination of oral and intravenous sedation has not been well investigated and this study examined the combination's effect on amnesia, anxiety, cardiovascular stability and recovery in a double blind, cross-over, placebo controlled trial. Patients were given 7.5 mg oral midazolam or placebo 1 h prior to intravenous midazolam and surgery. This investigation demonstrated significant anxiolysis, amnesia and patient preference for oral midazolam compared to placebo. There was no significant effect on cardiovascular stability, the intravenous dose of midazolam used or post-operative recovery. Low dose oral midazolam prior to intravenous sedation may be beneficial in very anxious patients, particularly if surgery is delayed. PMID- 1761876 TI - Orbital abscess of odontogenic origin. Case report and review of the literature. AB - A case is discussed of a patient with an orbital cellulitis and a post septal abscess secondary to infection from an upper molar tooth. Spread of infection was to the maxillary sinus and thence to the orbit via a defect in the orbital floor. The clinical presentation, differential diagnosis, value of CT scanning, treatment and possible complications are reviewed. PMID- 1761877 TI - Intravascular papillary endothelial hyperplasia of the mandibular mucosa. AB - Intravascular papillary endothelial hyperplasia (IPEH) usually presents as a cutaneous lesion consisting of a reactive proliferation of endothelial cells that arise in an organizing thrombus. This lesion can easily be mistaken for an angiosarcoma. Oral presentations are rare, and when they do occur the most common site is the lip. A rare case of IPEH affecting the mandibular buccal mucosa is described. PMID- 1761878 TI - True lateral dermoid cyst of the neck. AB - A case of a lateral dermoid cyst presenting in the submandibular triangle without previous intra-oral swelling is reported. Sonography provided the key to diagnosis and is the first investigation of choice. PMID- 1761879 TI - Traumatic carotid cavernous sinus fistula due to a gun shot injury. AB - A case of a traumatic carotid cavernous sinus fistula is presented, the result of a bullet passing through both condylar regions of the mandible. The fistula was occluded by a detachable balloon brought in place using endovascular techniques. PMID- 1761880 TI - Intermaxillary fixation using screws. Report of a technique. AB - A technique of intermaxillary fixation using screws anchored in the maxilla and mandible has been described. AO (Synthes) screws with a diameter of 3.5 mm and 12 mm to 16 mm in length were inserted at the antero-lateral surface of the maxilla and the buccal surface of the mandible. This technique is particularly suitable for mandibular fractures in denture wearing patients. PMID- 1761881 TI - Transfacial access for neurosurgical procedures: an extended role for the maxillofacial surgeon. I. The upper cervical spine and clivus. AB - A variety of osteoplastic flaps have been devised for transoral or extraoral access to the base of skull and the upper anterior cervical spine. Part I of this two-part review will describe access to the clivus and upper anterior cervical spine. Part II will describe access to the middle cranial fossa, the infratemporal fossa and the pterygoid (retromaxillary) "space". PMID- 1761882 TI - Transfacial access for neurosurgical procedures: an extended role for the maxillofacial surgeon. II. Middle cranial fossa, infratemporal fossa and pterygoid space. AB - A variety of osteoplastic flaps have been devised for transoral or extraoral access to the base of skull and the upper anterior cervical spine. Part I of this two-part review describes access to the clivus and upper anterior cervical spine. Part II will describe access to the middle cranial fossa, the infratemporal fossa and the pterygoid (retromaxillary) "space". PMID- 1761883 TI - Intravelar veloplasty: surgical modification according to anatomical defect. AB - The patient is often left with an oro-nasal fistula after the intravelar veloplasty procedure for the primary closure of the hard and soft palate cleft. The junction between the hard and soft palate is submitted to maximal tension during this procedure and is where the fistula most often occurs. The primary intravelar veloplasty procedure is discussed and 7 surgical modifications are introduced. The aim of these modifications is the prevention of an oro-nasal fistula and each is specifically adapted according to the existing anatomical form and defect of the cleft palate. The surgical modifications are divided into 2 main groups: those based on localised swivel flaps and those based on distant flaps. PMID- 1761884 TI - Altering the angulation of a curved osteotome--does it have effects on the type of pterygomaxillary disjunction in Le Fort I osteotomy? An experimental study. AB - A standard Le Fort I osteotomy was performed on 12 cadavers to determine whether the incidence of pterygoid plate fractures could be reduced by increasing the angle of the curved osteotome relative to the sagittal plane. In the group where an osteotome with the usual angulation was employed, fractures occurred on 9 of 12 sides. In the increased angulation group, 5 of 12 pterygoid plates were fractured. All fractures were restricted to the level of the horizontal osteotomy cut. It is concluded that increased angulation of a curved osteotome can decrease the incidence of fractures of the pterygoid plates. This procedure, however, is not recommended because it can cause fracture of the palatine bone or displacement of the fractured pterygoid plate fragment posteriorly. PMID- 1761885 TI - Resection of endonasal neoplasm by means of modified maxillo-zygomatic cheek flap. AB - To remove an endonasal tumour an access osteotomy has been designed which can be used for tumours of the nasal cavity. This approach allows for a safe and adequate tumour resection without appreciable morphological and functional consequences for the patient. PMID- 1761886 TI - Myxoid liposarcoma of the buccal vestibule. A case report. AB - A case of a myxoid liposarcoma in the buccal vestibule of the mandible is presented. The patient, an 86-year-old women, had 2 local recurrences after initial excision and died several months later. The literature is briefly reviewed. PMID- 1761887 TI - Penicillin concentration in the compact bone of the mandible. AB - During surgical removal of impacted third molars, the concentration of Penicillin G was determined in the compact bone of the mandible. Fifteen patients received 5 million IU and 15 received 10 million IU of Penicillin G intravenously as a single dose before surgery began. In both groups concentrations of penicillin with a bactericidal effect on most pathogenically relevant oral bacteria were detected during osteotomy. Taking into account the considerable interindividual variation, the one-shot application of 10 million IU of Penicillin G was more effective in certain cases than the 5 million IU dose. The factors influencing the decision on the high single-dose application include expected length of operation, body weight, kidney function, and infusion period. Assuming that in intraoral osteotomies the bone becomes contaminated with bacteria that are highly sensitive to penicillins, the results indicate that preoperative infusion of Penicillin G could be an effective method of preventing wound infection. PMID- 1761888 TI - Report on the 4th International Congress on Preprosthetic Surgery, Palm Springs, USA, 18-20 April, 1991. PMID- 1761889 TI - [Clinical study on ivermectin against Strongyloides stercoralis]. AB - We previously reported the efficacy of ivermectin (IVM) for the treatment of 23 strongyloidiasis patients. We now reported the efficacy and safety of IVM therapy on 54 patients. Fifty-four patients, 28 males and 26 females, received a single oral dose of IVM one hour before breakfast and this treatment was repeated 2 weeks later. The following results were obtained: 1) The cure rate at 2 weeks after the initial treatment was 92.5% (49 of 53 patients) and 2 weeks after the second course was 96.0% (48 of 50 patients). 2) Four patients (7.4%) complained of diarrhea (n = 2 patients), constipation (n = 1), borborygmus (n = 1), dizziness (n = 1), diplopia (n = 1) and peri-anal itching (n = 1) after the first treatment. Three patients (5.6%) complained of borborygmus (n = 1), itching (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 25.9% in the patients. As described above, although side effects occurred in some cases, they were mild and transient. From these results, we concluded that IVM is an effective drug for strongyloidiasis. PMID- 1761890 TI - [Clinical evaluation of serological antigen detection tests for candidemia]. AB - The new serological tests for candidemia were evaluated. In nine cases of candidemia, fungal index (Endotoxin D-Endospecy) was 146.8 +/- 116.8 pg/ml and D arabinitol/creatinine 1.10 +/- 1.04 mumol/mg. Fungal index was significantly (p less than 0.01) higher in candidemia than suspected infections. All candidemia were positive for Cand-Tec latex agglutination, but twelve of the sixteen cases of suspected infections were also positive. Mannan latex agglutination was very specific for candidemia. Four cases of candidemia was positive for Mannan latex agglutination and only one case was positive in suspected infections. Fungal index and D-arabinitol/creatinine was decreased after treatment of antifungal agents. In poor clinical efficacy case, these titer remained high even after treatment. These data suggested the usefulness of these serological tests for candidemia. PMID- 1761891 TI - [Clinical features of enterococcal septicemia and antimicrobial susceptibilities for clinical isolates of enterococci in Nagoya University Hospital]. AB - Enterococci are important causative organisms of nosocomial infections as well as methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa. Enterococcal bacteremia has been increased in Nagoya University Hospital from April 1983 to March 1990. We analyzed the clinical backgrounds, portal of entry and mortality for the patients with Enterococcal septicemia. Thirty-four cases with enterococcal septicemia (24 Enterococcus faecalis, 10 Enterococcus faecium) were subjected in this study. Twenty-seven cases were monomicrobial septicemia and 7 cases were polymicrobial septicemia. As to the portal of entry, intra abdominal infections in 21 cases, urinary tract infections in 4 cases, respiratory tract infections or chest tubes in 2 cases, decbitus infection in 1 case, intravascular catheter in 1 case, and unknown sources in 5 cases. Total mortality of the septicemia was 44.1%. E. faecium and Enterococcus avium were much more resistant to antimicrobial agents than E. faecalis. Enterococci with high-level resistance to gentamicin (minimal inhibitory concentration, greater than 2000 micrograms/ml) accounted for 35% of the 26 clinical isolates of enterococci. PMID- 1761892 TI - Virulence of Escherichia coli strains with R-plasmid mediated penicillin resistance in mice infections. AB - Penicillinase I-, II- and III-producing R-plasmid of Escherichia coli were transferred to Escherichia coli 177, KC-14, and 444. These strains are highly virulent in mice. This study was conducted to investigate the influence of conjugative R-plasmid on the virulence of its host strains. Escherichia coli 177 after penicillinase I- or III-producing R-plasmids transfer retained parental levels of virulence. On the other hand, penicillinase II-producing transconjugants showed reduced virulence in mice. The virulence of its revertants, in which R-plasmid was eliminated by heat, were equivalent to that of the host strain. It is suggested that the decrease in the virulence of transconjugants was not due to transferred R-plasmid. The reduced virulence of the these transconjugants may be due to alterations in their components such as the lipopolysaccharides in the cell envelope. PMID- 1761893 TI - [Nosocomial infections due to methicillin-resistant S. aureus (MRSA) at the Kagoshima University Hospital (1). Coagulase typing of MRSA]. AB - Nosocomial infection due to MRSA at the Kagoshima University Hospital and their coagulase typing were examined using S. aureus (349 strains) clinically isolated in 1989. The results were as follows: 1) S. aureus consisted of 43.6% of MRSA and 56.7% of Methicillin-sensitive S. aureus (MSSA). 2) MRSAs were recovered most frequently from the specimens from the respiratory tract (47.8%). 3) The isolation of MRSA gradually increased in frequency from January to August; however, that of MSSA did not show a similar tendency. 4) The isolation of MRSA was higher in frequency in the surgical wards, the ICU and the pediatric ward. 5) When classified into 8 coagulase types, MRSAs (133 strains) consisted of only 3 types (54.1% of type II, 32.3% of type VII, and 12.0% of type IV), whereas MSSAs contained all coagulase types. As compared with the results of coagulase typing at other institutions, the incidence of type VII was much more frequent at our hospital. 6) A few coagulase types of MRSA appeared in each ward. Also, type II MRSA strains increased in June and July, and type VII MRSA increased in August. However, MSSA strains did not show any similar tendency. PMID- 1761894 TI - [Nosocomial infections due to methicillin-resistant S. aureus (MRSA) at the Kagoshima University Hospital (2). Susceptibility to antibiotics]. AB - Susceptibility to antibiotics of 123 MRSA strains isolated at the Kagoshima University Hospital in 1989 was examined. The results were as follows: 1) Susceptibility of MRSA strains was excellent to VCM, MINO, and RFP, followed by IMP, CLDM, and CPFX. However, most strains were resistant to PCG, MPIPC, ABPC, CET, CMZ, CZON, GM, and AMK. 2) Five strains highly resistant to RFP were isolated. Three of these strains were isolated on the ward for tuberculosis. This suggests easy development of resistance to RFP by MRSA. 3) Differences in susceptibility to antibiotics between coagulase type II and type VII strains were examined. The cumulative percentage of type II strains susceptible to CLDM (MICs less than 0.5 microgram/ml) was 15.3%, and that of type VII was 45.2%. Strains resistant to CLDM were more frequently isolated among type II than among type VII strains (p less than 0.001). A similar relationship between strains and antibiotics was also found with EM and CPEX. On the other hand, the cumulative percentage of type II strains susceptible to AMK (MICs less than 25 micrograms/ml) was 89.7%, and that of type VII was 9.7%. Strains resistant to AMK were more frequently isolated among type VII than among type II strains (p less than 0.001). PMID- 1761895 TI - [A clinical experience of rokitamycin on Campylobacter enteritis. Research Group of Rokitamycin on Infectious Enteritis]. AB - Rokitamycin, a newly developed macrolide, was administered to a total of 107 cases, 16 years old or more, in order to evaluate its clinical efficacy, safety and usefulness on Campylobacter enteritis. Daily dosage of 600 mg of rokitamycin was administered orally in three divided doses for 5 days. Bacteriological and clinical efficacies were judged by the attending doctors from the evaluation criteria made by the committee and from the days required for improvement of diarrhea, defervescence and so on, respectively. Antibacterial activities against the isolates were tested of rokitamycin (RKM), erythromycin (EM), josamycin (JM) and ofloxacin (OFLX). The results were as follows; 41 symptomatic patients and 5 carriers were evaluated. Clinical efficacy (n = 41) was 100% (excellent; 34.1%, good; 65.9%). Bacteriological efficacy (n = 41) was 97.6%. Eight of the 9 cases with consecutive stool cultures were free of the bacteria on and after one day of the drug administration. Clinical usefulness (n = 46) was 97.8%. Slight epigastric pain was seen in only one as a side effect. The items of abnormal laboratory findings were 4 elevated GPT and/or GOT and one increased number of WBC in 4 cases. MIC90 of RKM, EM, JM and OFLX against 41 clinical isolates of C. jejuni were 1.56, 3.13, 3.13 and 0.78 micrograms/ml, respectively. Rokitamycin was considered clinically useful to treat Campylobacter enteritis. PMID- 1761896 TI - [Comparison of clinical efficacy of rokitamycin (RKM) and ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double-blind method. The Research Committee for the Effect of Rokitamycin, Research Group for Infectious Enteritis]. AB - The clinical efficacy, safety and usefulness of Rokitamycin (RKM), a new macrolide antibiotic, were compared with those of Ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double blind method. The daily dose level of RKM or OFLX was 600 mg. They were orally administered in three divided doses for 5 days. Of 223 cases studied, 106 cases were diagnosed as Campylobacter enteritis. Ninety cases (RKM group: 50, OFLX group: 40) except for 16 excluded or drop-out cases were analysed. There was no significant difference between the two groups in any background factors. The effectiveness and usefulness was evaluated in 88 cases (RKM group: 48, OFLX group: 40). The results obtained were as follows: 1. In a total of 82 strains of Campylobacter jejuni/coli (RKM group: 42, OFLX group: 40), the bacteriological efficacy rate of RKM (95.2%) was superior to that of OFLX (70.0%) with a significant difference (p = 0.006). 2. In 76 symptomatic patients (RKM group: 42, OFLX group: 34) on the day of the beginning of drug administration, the clinical efficacy rate was 97.6% in the RKM group and 85.3% in the OFLX group with no significant difference between the two groups. 3. In 88 evaluable patients, the global clinical efficacy rate of RKM (95.8%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.001). 4. Side effect was observed in 1 (1.9%) of the 54 patients in the RKM group and none of the 44 patients in the OFLX group. Slightly abnormal laboratory findings were seen in 4 (10.8%) of the 37 patients treated with RKM and 3 (9.7%) of the 31 patients treated with OFLX, but there was no significant difference between the two groups. 5. In 88 evaluable patients, the clinical usefulness of RKM (91.7%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.01). From these results, RKM is considered to be a very useful agent for the treatment of Campylobacter enteritis. PMID- 1761897 TI - [Detection of Chlamydia trachomatis by polymerase chain reaction]. AB - A polymerase chain reaction (PCR) procedure was developed for detection of Chlamydia trachomatis. Two oligonucleotide primers based on sequences within the major outer membrane protein gene from C. trachomatis serovar L2 were used. A single DNA fragment was amplified, when C. trachomatis DNA was template for the PCR. No amplified product was detected in Chlamydia psittaci DNA, Chlamydia pneumoniae DNA or other bacterial DNAs. The amplified DNA fragment was detected, when DNA of greater than or equal to 10(2) C. trachomatis per reaction was used as template for the PCR. Thus, the PCR was shown to be specific for C. trachomatis and more sensitive than the enzyme immunoassays for detection of chlamydial antigen and the chlamydial rRNA:DNA probe hybridization method. PMID- 1761898 TI - [A case report of siblings with hemolytic uremic syndrome from whose stool E. coli O157:H7 was isolated]. AB - We experienced siblings of hemolytic uremic syndrome which occurred following diarrhea and bloody stool. They were immediately treated with dipyridamole and aspirin, and recovered from hemolytic uremic syndrome in about two weeks. E. coli O157:H7 (verotoxin producing E. coli) which is recently thought to be related to the pathogenesis of hemolytic uremic syndrome was isolated in their stool cultures on admission. As far as we know, this is the first case in Japan from which stool E. coli O157:H7 was detected. Moreover, we reported clinical effectiveness of genomic investigation utilizing polymerase chain reaction method for verotoxin coding region in a rapid diagnosis of this bacterial infection. PMID- 1761899 TI - [Hospital spread of scabies from an immunocompromised patient with Norwegian scabies]. AB - Scabies was first found in a 71-year-old female who had been diagnosed as having leukemic transformation of primary myelofibrosis and had undergone treatment for the disease. She was admitted to the hospital in December 1986, because of abdominal fullness and a generalized subcutaneous tumor that proved to be myeloblastoma. For treatment of the underlying disease, the regimen of the combination of vindesine, cyclophosphamide, 6-mercaptopurine, and prednisolone was selected. She developed cardiac failure and fell into a coma one month after starting the anticancer therapy. She was put on artificial respiration and on additional steroid therapy as well. Dexamethasone was administrated at 16 mg/day. Since the myeloblastomas found on admission regressed, the steroid therapy was continued. She was in coma for a few days before her skin lesions turned red and formed a grayish crust in the lower abdominal region. Several days later, the doctor responsible for the treatment of this patient developed pruritus and exanthema on both arms, and soon many nurses in the same hospital-ward developed similar symptoms. At approximately the same time, the patient with myelofibrosis was diagnosed as having Norwegian scabies: the crusted skin lesions revealing many Sarcoptes scabiei mites. Two doctors (2/18), 17 nurses (17/19) and 3 other patients (3/51) were found to have contracted scabies, and we recognized the hospital spread of the infection. The first patient was isolated in a private room, and we avoided direct contact with her. The persons with scabies were treated with crotamiton liniment. The first scabies patient died of cardiac failure 1 month after falling into a coma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761900 TI - [Effect of fluconazole on Aspergillus infection associated with chronic granulomatous disease]. AB - Aspergillus infection is the most frequent fungal infection associated with chronic granulomatous disease (CGD), and often results in a life-threatening situation. This report describes the use of high-dose fluconazole, a new antifungal agent, for invasive Aspergillus infection in a patient with CGD. A 27 month-old boy was sent to our hospital because of unknown fever in October, 1988. He was then admitted for pneumonia and pleural effusion of the right lung in February, 1989. Treatment with antibiotics was ineffective, and cultures of throat and pleural fluid were negative. In May, 1989, Aspergillus fumigatus was cultured from a subcutaneous abscess at the point of pleural puncture. Therefore we speculated that Aspergillus might have been the cause of pneumonia. The patient was diagnosed as having CGD by NBT test. Treatment with miconazole, flucitocin and amphotericin-B syrup was ineffective. From July, 1989, he was given 100 mg/day fluconazole d.i.v., but the drug did not reach an effective serum concentration to combat Aspergillus. However, an effective concentration of fluconazole was reached at a dose of 250 mg/day, and the chest X-ray findings subsequently improved, despite occasional high fever and continued high CRP. In July, 1990, the route of fluconazole administration was changed from d.i.v. to p.o. at the same dose, resulting in a serum concentration of fluconazole higher than that achieved with d.i.v. treatment. Both the clinical and laboratory findings showed improvement thereafter. Therapy for Aspergillus infection associated with CGD was found to necessitate high doses of anti-fungal drugs over a long period, although treatment with previously employed anti-fungal drugs could not be continued due to their adverse side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1761901 TI - [Hafnia alvei septicemia with shock and DIC in an adult with postoperative lung cancer]. AB - In Japan, we experienced the first case of Hafnia alvei septicemia with shock and disseminated intravascular coagulation (DIC) in an adult with postoperative lung cancer. A 63 year-old male, who had been followed up in our department since 1987, was admitted to our hospital with the complaints of fever, hemoptysis and dyspnea on June 25, 1989. After admission, he was treated with sulbactam/cefoperazone 4 g/day intravenously for suspicion of respiratory-tract infection. After antibiotic administration, the fever subsided and the general condition became almost good. The patient experienced fever again after the antibiotic was stopped. For this reason subsequent Clavulanic acid/Amoxicillin, Flomoxef, and Ceftazidime was administered, but was not effective. Therefore septicemia was suspected and blood culture was done. The bacteria isolated from blood culture was identified as Hafnia alvei. Hafnia alvei is a gram-negative organism belonging to the Enterobacteriaceae family and quite rare pathogen in human. PMID- 1761902 TI - Biomechanical study of Chiba Solid Rod System for scoliosis surgery. AB - The Chiba Solid Rod System for three-dimensional correction of scoliosis was developed. The system consists of a 7 mm diameter smooth solid rod, closed and open hooks, and specially designed conical sleeves. The rod does not have ratchets, thus minimizing stress concentrations. The hooks are attached to the rod utilizing the conical sleeves. The inner surface of the hooks and the outer surface of the conical sleeves have precisely machined tapers of two degrees. The sleeves have longitudinal slits permitting compression during insertion. The purpose of this study is to evaluate quantitatively the strength and stability of the system. Axial compression tests, torsional tests, and cyclic axial compression tests up to ten million cycles were performed to evaluate the attachment of the hook to the rod. Mechanical testing protocols demonstrated the effective attachment of the hook to the rod. Furthermore, simulation tests using scoliosis-simulation models were carried out. The single rod system of the Chiba Solid Rod System was appropriate for stabilizing a curvature of 30 degrees (Cobb). However, the dual rod system of the Chiba Solid Rod System was necessary to stabilize a curvature of 50 degrees or more. PMID- 1761903 TI - [Periosteal osteosarcoma of the femur: a pathological and ultrastructural study]. AB - A femoral, diaphyseal tumor was found in a 17-year old male, and the diagnosis of periosteal osteosarcoma was made, based on the typical radiological and pathological findings. Microscopic observation on a resected specimen revealed that the tumor was covered with the intact periosteal fibrous layer and did not extend beyond the periosteum. The adjacent cortex was free of tumor. These findings indicated that the tumor originated from the periosteal cambium layer, which lies between the periosteal fibrous layer and the cortex. For transmission electron microscopic examination, the tissue was obtained at open biopsy. Ultrastructurally, no specific cell of periosteal osteosarcoma was found. Although most types of osteosarcoma cells were identified in the tumor (osteoblast-like, chondroblast-like, fibroblast-like, primitive mesenchymal-like, osteoclast-like and so on), the ultrastructural characteristics were of wide variety and of low malignancy. PMID- 1761904 TI - Clinical significance of the straight-leg-raising test. AB - The results of conventional sciatic nerve stretching tests are usually evaluated regardless of patient age, gender or movements of the hip joint and spine. In this study, we correlated data on the leg raising angle and changes in tension signs according to age, gender, and movement of the pelvis during the SLR-test and Lasegue-test. Results suggest that increased tension in the pelvic and leg muscles due to rapid skeletal growth contributes to the limited range of SLR in growing persons, while the Lasegue-test is less influenced by age and shows less pelvic rotation than the SLR-test. PMID- 1761905 TI - [Ferrographic analysis of synovial fluid in total hip replacement]. AB - A synovial fluid analysis was carried out on 84 patients with total hip replacements, 53 of which were revision cases. The analysis was done using ferrography. An animal study was carried out whereby alumina ceramic, polyethylene and polymethyl methacrylate particles were inserted into the knees of rabbits, the synovial fluid of which was analysed. In addition, the synovium and surrounding tissues were histologically analysed. One week after insertion of the particulate debris only a few particles were noted in the synovial fluid and none at two weeks post insertion. However, these particles were noted in the synovium and surrounding tissues. Therefore, it was concluded that wear particles, following total hip replacement, may be encapsulated in the early period by the capsule and synovium, and have no adverse affect on the lubricating kinetics of the joint. It is postulated that the difference in tissue reaction to each of these particles may be responsible for the subsequent loosening. PMID- 1761906 TI - [A study of degenerative changes in the triangular fibrocartilage of the wrist joint]. AB - The present investigator has studied the degenerative changes in the triangular fibrocartilage (TFC), the articular cartilage of the wrist joint, and the carpal interosseous ligament. Moreover, the possibility of the healing of the TFC was examined. The materials were 162 wrist joints obtained from 99 cadavers (5; fresh, 94; preserved) and were studied radiographically, anatomically, pathologically and immunohistochemically. TFC perforation was correlated with ulnar variance. Cartilaginous changes were mainly found around the lunotriquetral interosseous ligament. There was a correlation between the TFC perforation and degenerative changes of the articular cartilage. The pathological finding showed the degenerative changes on the ulnar head side of the TFC, which were much more severe than the carpal side of the TFC. On the other hand, the cartilaginous changes were more severe in the carpal bones than in the distal ulnar head. The finding that central portion of the TFC was found to be avascular, as confirmed by the immunohistochemical method would indicate little possibility of healing of the central portion of the TFC. PMID- 1761907 TI - Mechanical strength of osteochondral junction. AB - The junction between articular cartilage and bone in adult humans was tested in shear to determine their bonding strength in relation to the tensile strength of full thickness articular cartilage and shear strength of underlying subchondral bone. The site of failures was also studied under light microscope and scanning electron microscope. The junction failed at a shear strength of 7.25 +/- 1.35 MPa (n = 18). On the other hand, the tensile strength of cartilage and shear strength of subchondral bone were 3.75 +/- 0.75 MPa (n = 17) and 2.45 +/- 0.85 MPa (n = 15) respectively. Light and scanning electron microscopic examination revealed that in fact, failures occurred at the tidemark. The ultrastructure of the tidemark suggested that this region might have structural weakness against mechanical stresses. The relevance of the results were discussed in relation to the osteochondral fractures in adult humans. PMID- 1761908 TI - [Pathological studies on the lumbar facet joints]. AB - Relationship between changes of the bony architecture and remodeling in the facet joints of the lumbar spine was studied in cadaveric specimens, using the method of microradiography. The facetal angle was 59 degrees at L1-2, 65 degrees at L2 3, 75 degrees at L3-4 and 92 degrees at L4-5. The subchondral compact bone volume was higher at the anterior part in all cases. The greater compact bone volume was found in the more sagittally facing facets, asymmetrical facets and facets with disc degeneration. Highly mineralized tissues in the trabeculae were observed in the degenerative facets. These tissues consisted of old calcified fibrocartilage, left alone as the result of continued remodeling. The degenerative changes in the lumbar facet joints probably start as calcification of the part where the ligamentum flavum attaches, followed by new bone formation and transformation of the joints. PMID- 1761909 TI - [Histological and mechanical observations of interconnection between sintered porous hydroxyapatite and Achilles tendon in rats]. AB - Sintered porous hydroxyapatite blocks (3 x 3 x 4 and 5 x 5 x 5) were implanted into the calcaneal tendons of 64 Wistar rats to observe tissue reaction and interconnection. Histological observations and measurements of mechanical strength of the interconnection were performed at 1 to 24 weeks after the implantation surgery. The implants were found to be surrounded by connective tissue consisting of small, round cells which infiltrated into micropores of the hydroxyapatite blocks. Neither calcifications nor inflammatory reactions were observed. The mechanical strength at the interconnection increased significantly from 1 week to 8 weeks after the implantation, which then reached the peak of 1.3 +/- 0.3 kg/cm2 at 8 weeks. PMID- 1761910 TI - [Study on reconstruction of the anterior cruciate ligament in the monkey knee using polyester artificial ligament]. AB - We performed an experimental study of ACL reconstruction utilizing polyester artificial ligament(Leeds-Keio). The quality of regenerated ligaments was compared between two different procedures; in the one 1 cm wide Leeds-Keio ligament was used alone for reconstruction(Group 1) and in the other, Leeds-Keio ligament of the same size was augmented with one-third width of free patellar tendon (Group 2). Eighteen knees of nine Japanese monkeys were used. The specimens were obtained at 2, 6 and 12 months after the operation and investigated macroscopically, microscopically and biomechanically. Regenerated ligaments in Groups 1 and 2 appeared identical and grossly normal. However, more mature and stable ligament was noted in the cylinder of artificial ligaments after 2 months after operation in Group 2 than in Group 1 in terms of both quality and quantity. Biomechanically, however, the maximum the tension in the regenerated ligaments was approximately 1/2-1/3 of that of normal ACL. The authors believe that more mature ligament was made in ACL reconstruction when the artificial ligament was augmented with autogenous soft tissue. PMID- 1761911 TI - [Haematogenous osteomyelitis induced by strain SMU-0611 of Staphylococcus warneri in mice]. AB - Strain SMU-0611 of Staphylococcus warneri isolated from clinical specimens (1.25 x 10(9) colony forming units) was intravenously administered into mice. Strain SMU-0611 caused remarkable inflammation characterized by roentgenographically recognizable changes in bone at 14 days after the injection. A number of organisms were detected in the bone marrow for as long as 35 days after the injection, suggesting specific lodgement of the strain in mouse bone marrow. Concerning the X-ray features of the mice, multiple foci of osteolytic changes were shown in the metaphysis of the femur and the tibia obtained 14 days after the injection. However, these changes did not aggravate at all for 56 days after the injection. PMID- 1761912 TI - [Roentgenological and pathological studies on the development of discitis in canine models]. AB - Discitis was experimentally induced in 42 dogs by intradiscal injections of bacterial suspensions and sequentially studied by X-rays and histopathology up to 24 weeks. 1. A narrowing of the serpentine intervertebral disc space was seen roentgenologically in the Pseudomonas and E. coli groups. 2. Histologically, the acute inflammation began to subside in eight weeks, at which time new bone formation started to appear, and fusion of the adjacent vertebrae became apparent in eight weeks. The degree of the disease process was more advanced in the Staph. aureus group and less severe in the Pseudomonas group. The E. coli group lay in between. 3. The inflammatory process seemed to be confined in the disc for a week after the injection, during which time the cartilagenous cells in the nucleus pulposus underwent atrophy and degeneration. This resulted in direct exposure of the cartilagenous plate to the infection, causing invasion of the inflammatory process into the vertebral body. 4. The presence of the epiphyseal line, however, seemed to act as a barrier to hinder the inflammatory process invading the vertebral body. PMID- 1761913 TI - [Bone lengthening: essential concepts and methodology]. PMID- 1761914 TI - [Vascularized bone graft]. PMID- 1761915 TI - [Selection of containment treatment for Legg-Calve-Perthes disease]. PMID- 1761916 TI - [Alpha 2-plasmin inhibitor]. PMID- 1761917 TI - [Cytokines and diseases. Clinical applications of RhG-CSF]. PMID- 1761918 TI - [Cytokines and diseases. Interleukin-2 and its receptor in adult T cell leukemia]. PMID- 1761919 TI - [Cytokines and diseases. Abnormal expression of interleukin 6 and diseases]. PMID- 1761920 TI - [Cytokines and liver diseases]. PMID- 1761921 TI - [Diabetes mellitus and its complications in Japan. Clinical profile of diabetic retinopathy in Japanese diabetics]. PMID- 1761922 TI - [Diabetes mellitus and its complications in Japan. Clinical and pathological finding and their relationship to prognosis in diabetic nephropathy]. PMID- 1761923 TI - [Diabetes mellitus and its complications in Japan. Late complications of diabetes mellitus--estimation of risk factors in patients on sulfonylureas (Su) more than 10 years]. PMID- 1761924 TI - [Diabetes mellitus and its complications in Japan. The determination of glycemic threshold for the regression or prevention of diabetic microangiopathies, and insulin injection regimen to establish strict glycemic control in NIDDM]. PMID- 1761925 TI - [Diabetes mellitus and its complications in Japan. The dysfunction of mesangial cells on pathogenesis of diabetic nephropathy]. PMID- 1761927 TI - [Diabetes mellitus and its complications in Japan. Pathogenesis and correspondence of diabetic retinopathy--approach from polyol metabolism]. PMID- 1761926 TI - [Diabetes mellitus and its complications in Japan. The pathophysiology and etiology of diabetic osteopenia]. PMID- 1761928 TI - [Myocarditis, clinical features and management]. PMID- 1761929 TI - [Recent advances and practice of psychosomatic medicine]. PMID- 1761930 TI - [Management of chronic respiratory insufficiency]. PMID- 1761931 TI - [Detoxification function of the liver]. PMID- 1761932 TI - [Altered vascular reactivity in hypertension]. PMID- 1761933 TI - [Roles of arachidonic acid cascade and related substances in respiratory diseases]. PMID- 1761934 TI - [Clinical aspects of hyponatremia]. PMID- 1761935 TI - [The development and clinical application of erythropoietin]. PMID- 1761936 TI - [Vasculitic syndrome]. PMID- 1761937 TI - [Secondary cardiomyopathy associated with myopathy]. PMID- 1761938 TI - Emergency cricothyrotomy. AB - The indications for the ruling for the Gulf Forces that emergency cricothyrotomy is to be performed where the airway is thought to be compromised are reviewed. The advantages of this procedure are outlined and some of the likely consequences regarding the incidence of complications and their management predicted. PMID- 1761939 TI - Human temporal bone findings in acquired hypothyroidism. AB - Histological studies of the auditory organ in patients with acquired hypothyroidism are scarce. Thus the aim of the present study was to examine the temporal bones and the brain in subjects with hypothyroidism. Four temporal bones and two brains from clinically and biochemically hypothyroid subjects were removed and evaluated by light microscopy determine to the morphological changes and deposition of neutral and acid glycosaminoglycans. An audiogram from one of the patients showed a sensorineural hearing loss, which could be ascribed to occupational noise exposure. The study revealed histological changes compatible with age and infectious disease. No accumulation of neutral or acid glycosaminoglycans could be demonstrated in the temporal bones, or in the brains. PMID- 1761940 TI - Blast injuries of the ear as a result of the Peterborough lorry explosion: 22 March 1989. AB - The incidence of blast trauma to the ears in significant numbers is relatively rare in peace time. This paper outlines the results and management of twenty patients injured as a result of the outside explosion of 800 kg of high explosives in Peterborough on 22 March 1989. PMID- 1761941 TI - A comparison of performance of Shepard and Sheehy collar button ventilation tubes. AB - This study was designed to confirm the longer in situ life of the Sheehy collar button compared with the Shepard tube and to assess the complication rates associated with the two tubes. Cases of bilateral otitis media with effusion had a Shepard tube inserted in one ear and a Sheehy contralaterally. The insertion position was allocated randomly. The patients were then assessed at three-monthly intervals for two years. In 71 per cent of those in whom at least one tube had extruded, the Sheehy remained in situ longer. The antero-inferior tube remained longer than the postero-inferior whichever type was used. There was no significant difference between complication rates, or recurrence rates of middle ear effusion after tube extrusion, for the two types. We conclude that use of a Sheehy rather than a Shepard tube carries no increased risk of complications and the patient may require further surgery less often in total. PMID- 1761942 TI - Obliterative otosclerosis. AB - An analysis of 420 consecutive cases of obliterative otosclerosis seen in the Christian Medical College Hospital, Vellore is presented. The proportion of truly obliterative otosclerosis is 33.09 per cent (139 ears). Our male to female ratio in truly obliterative otosclerosis is 1.48:1, while in the non-obliterative group it is 1.34:1. The mean age at onset in the obliterative group was 19.14 while in the non-obliterative group it was 25.60. This is statistically significant (P less than 0.001). The age at presentation was 25.90 in the obliterative group while in non-obliterative group it was 30.86; this is also statistically significant (P less than 0.001). However the time interval between the age at onset and the age at presentation is not statistically significant. PMID- 1761943 TI - Non-ampullary plugging of the posterior semicircular canal for benign paroxysmal positional vertigo. AB - Benign paroxysmal positional vertigo (BPPV) is a common condition which is usually self-limiting. Surgical treatment is rarely required and for many years the mainstay of such treatment has been singular neurectomy (posterior ampullary nerve section). A new operation has recently been described for the treatment of BPPV involving occlusion of the posterior semicircular canal. We have performed this operation on five patients with intractable BPPV and report our results with follow up of between 12 and 36 months from operation. The excellent results of posterior semicircular canal occlusion which have been previously reported in the literature are confirmed by our experience. In our opinion the operation is a safe and effective alternative to singular neurectomy. PMID- 1761944 TI - Role of surgery in tuberculous mastoiditis. AB - A study was undertaken in 43 patients to determine the role of surgery in tuberculous mastoiditis. Cortical mastoidectomy was performed on five patients (Group I). Incision and drainage of a post-auricular abscess, removal of sequestrum and meatoplasty in eight (Group II). Thirty patients had no ear surgery (Group III). Of the 17 patients with facial palsy, three were in Group I, two in Group II, 12 in Group III. The patients in all three groups were treated with anti-tuberculous drugs for a period of no less than six months. The average time taken for the otorrhoea to subside and granulation tissue to resolve completely was two months in all three groups. The facial nerve recovery in the non-operated ears (Group III) was 92 per cent and in the operated ears (Group I and II) 80 per cent. The conclusion is that chemotherapy is the management of choice in tuberculous mastoiditis. The only role of surgery is incision and drainage of a post-auricular abscess and removal of sequestrum if present. PMID- 1761945 TI - Fronto-ethmoidal mucocoeles: a histopathological analysis. AB - From a series of 118 fronto-ethmoidal mucocoeles, 40 specimens have been submitted to detailed histological analysis. The frequency of each epithelial and sub-epithelial component is considered and reveals features which support a dynamic theory of bone resorption and formation rather than that of pressure erosion in the pathogenesis of mucocoeles. PMID- 1761946 TI - Lymphangioma of the tongue. A review of pathogenesis, treatment and the use of surface laser photocoagulation. AB - Lymphangiomas of the tongue are rare tumours. Several reports of this interesting condition have appeared in the literature with varying modalities of treatment being employed to control tongue size. We present here our experience with seven children who have lymphangiomas of the head and neck with tongue involvement seen over the past eight years. If the tongue is large with protrusion outside the lip margins, we advocate early tongue reduction so as to promote proper speech and deglutition, reduce orthodontic problems and achieve good cosmesis. However, the natural history of these tumours is one of recurrent tongue enlargement secondary to infection and trauma, irrespective of surgical reduction. We describe our technique of surface CO2 laser photocoagulation which has been successfully employed in controlling tongue size and removing superficial lymphangioma in all our patients. We propose therefore that this should be the mainstay of follow-up therapy in lingual lymphangiomas. PMID- 1761947 TI - Laryngeal preservation in cases of advanced laryngeal cancer treated with platinum based induction chemotherapy before local treatment. AB - In this study we analyse our preliminary results after treating 28 patients with locally advanced laryngeal cancer with platinum based induction chemotherapy followed by radiation therapy or surgery. The median age of our patients was 60 (46-75) years and median performance status was 80 (60-100). In 18 of the 28 patients locoregional treatment was radiation therapy with an overall response of 94.4 per cent. After a median follow-up of 26 (15-40) months 39.3 per cent of the whole group of patients are alive and disease-free and six (21.4 per cent) patients are alive and disease-free preserving their larynx. We conclude that although more extensive studies with large groups of patients and longer follow up is needed to reach definite conclusions, it seems that platinum based induction chemotherapy can be used successfully in locally advanced laryngeal cancer followed by radiotherapy. In those cases who respond well, the patient's larynx is preserved without compromizing the overall survival. PMID- 1761948 TI - Laryngectomy: the patient's view. AB - The disabilities following laryngectomy are well recognized. The incidence of these disabilities and the acceptability of the surgery to the patients were assessed by a questionnaire method. Sixty-five patients participated in the study. The incidence of disabilities are discussed. Total laryngectomy was felt to be a worthwhile operation by most of the patients in the study despite the disabilities they experienced afterwards. PMID- 1761949 TI - Survey of immunosuppressive acidic protein and other immunological parameters in head and neck cancer patients. AB - Serum levels of immunosuppressive acidic protein (IAP) and other immunological parameters were examined in 95 head and neck cancer patients and 27 control patients. The mean values of IAP in patients in the advanced stage were significantly higher than in early stage patients. Statistically significant increases in the mean concentration of IAP were also observed in patients with a recurrence, as compared to findings in those in the advanced stages. The mean values of blastogenesis response to PHA and NK cell activity in the cancer patients were lower than in disease free individuals, but with no statistical differences. In the endstage patients, the IAP concentration was considerably elevated and the blastogenesis response showed a statistically significant decrease. Thus, the monitoring of serum IAP, in combination with other immunological parameters, aids in planning and assessing clinical staging in head and neck cancer patients. PMID- 1761950 TI - The laryngeal box: an aid to laser microlaryngeal surgery. PMID- 1761951 TI - Orf of the pinna. AB - A case of orf affecting the pinna is discussed. This is an unusual presentation of an infection that is common in farming communities. At the initial presentation the diagnosis was not suspected, the management therefore was inappropriate and probably gave rise to the secondary infection that ensued. The history described is classical. Orf affecting the external auditory canal has been reported once, but orf affecting the pinna has not been described before. PMID- 1761952 TI - Aggressive papillary middle ear tumour. AB - A rare middle ear tumour is reported. The clinical presentation was similar to that of a glomus tumour but the pathology that of an aggressive papillary middle ear tumour. This is a recently recognized subgroup of middle ear glandular tumours. Clinical findings, imaging, pathology and treatment are presented. PMID- 1761953 TI - Cutaneous sebaceous gland carcinoma in the postauricular region. AB - Carcinomas of the sebaceous glands of the skin are uncommon. These tumours metastasize frequently. A case of cutaneous sebaceous carcinoma localized in the postauricular region is presented with its exceptional large size and very poor prognosis. PMID- 1761954 TI - Adenoidectomy in a girl with haemophilia. AB - Haemophilia A is a sex-linked inherited disease in which those affected are usually males, and females are usually asymptomatic carriers. This paper presents a haemophilia A carrier who has a low factor VIII level first, to remind readers that females can have low factor VIII levels with consequent increased tendency to bleed; second, to stress the importance of routine questioning regarding a bleeding tendency in the patient or the patient's family and third, to illustrate the importance of pre-operative diagnosis to allow adequate correction of the defect so that surgery such as adenoidectomy can be undertaken with safety in such a patient. PMID- 1761955 TI - Sphenoid sinus mucocoele: a possible late complication of radiotherapy to the head and neck. AB - A case of sphenoid sinus mucocoele following radiotherapy in a patient with nasopharyngeal carcinoma is reported. Diagnosis was made by radiological investigation and confirmed at surgery performed via a sublabial transeptal approach. Its content was completely removed and continuous drainage of the sinus was maintained by an indwelling tube. It is felt that the sphenoid mucocoele developed as a result of occlusion of the sinus ostium by scarred mucosa following radiotherapy. PMID- 1761956 TI - Relapsing polychondritis presenting with stridor from bilateral vocal cord palsy. AB - A case of bilateral vocal cord palsy caused by relapsing polychondritis is presented. The diagnosis was not suspected preoperatively and was made solely on histopathology. A case is made for histological examination of cartilage removed during routine tracheostomy. PMID- 1761957 TI - Styloid apparatus anomaly causing dysphagia. AB - An unusual case of dysphagia due to anomalous styloid apparatus anatomy is presented. Clinical and radiological findings are documented. Variations in anatomy and clinical syndromes are discussed together with management. PMID- 1761958 TI - Salmonella neck abscess associated with jugular vein thrombosis. AB - An unusual case of synergistic infection caused by Salmonella paratyphi and anaerobic streptococcus resulting in necrotizing cervical infection associated with deep neck abscess and internal jugular vein thrombosis, is presented. Salmonella acting as an oxygen consumer in the infected tissues, facilitates the growth of anaerobic cocci, hence the development of a devastating soft tissue infection. The precipitating cause was a tonsillar infection developing due to 'post-anginal sepsis'. The aetiopathogenesis of the cervical infection is discussed. PMID- 1761959 TI - Radiological diagnosis of rhinoscleroma--the 'palatal sign'. AB - This paper reports a characteristic radiological finding observed in seven cases of rhinoscleroma with nasal involvement. The soft palate exhibits a marked thickening at its attachment to the hard palate which tapers off towards its free edge. This new sign could be of help in the early diagnosis of this condition. PMID- 1761960 TI - How to disclose imminent fracture of brazing alloy in a tracheostomy tube. PMID- 1761961 TI - The inter- and intraexaminer reliability of the Gonstead pelvic marking system. AB - An investigation was undertaken to determine the inter- and intraexaminer reliability of the Gonstead pelvic radiographic marking system. This methodology analyzes the relative dimensions and spatial positions of the two innominate bones and sacrum and measures leg length inequality through an evaluation of femur head height. Two examiners marked 71 full spine radiographs twice to provide data from 284 analyses. Reliability was ascertained with the Pearson r, Spearman, intraclass correlation coefficient (ANOVA) and Kappa statistics. All results were statistically significant (less than 0.001) and indicated high levels of concordance. In every case, intraexaminer agreement was superior to interexaminer concordance. PMID- 1761962 TI - A new approach to testing of long-term resistance of the spine to mechanical stress. AB - This paper studies the movement of the cervical spine from a side-bending to a return to the neutral position. The importance of muscular and ligamentous elements of the spine are emphasized. Directions for future research are noted. PMID- 1761963 TI - The reliability of specific sacro-occipital technique diagnostic tests. AB - Four interexaminer and one intraexaminer agreement studies were performed on specific diagnostic tests commonly employed within sacro-occipital technique (SOT). Ten of the tests were evaluated in more than one interexaminer study. Of these, only one test (bilateral supine leg raise with cervical compaction) had at least fair reliability more than once. Six of these 10 tests obtained poor agreement in more than one study. One examiner out of two had a number of excellent and fair intraexaminer values, whereas the other examiner generally had poor results. There may have been some treatment effect as a comparison of the combined intraexaminer diagnosis for two observers after no treatment and after treatment showed that the repeatability diminished from Kappa of 0.36 in untreated cases (which were expected to have high agreement of before and after treatment findings) to a Kappa of 0.27 for those subjects having received treatment (which were expected to have low agreement of before and after treatment findings). It appears unlikely that SOT tests can be reproduced to a sufficiently high degree to constitute useful clinical procedures. PMID- 1761964 TI - The radiology of cervical spine injury. AB - Cervical spine injury is a frequent sequelae of accidental trauma. Clinical evaluation often fails to raise adequate suspicion of an underlying injury. Radiologic assessment frequently reveals recognizable signs of damage ranging from fractures to joint and soft tissue injuries. This paper reviews the pathomechanics, clinical and radiologic features of the most common patterns of cervical spine injury. PMID- 1761965 TI - Is there a chiropractic science? PMID- 1761966 TI - A retrospective consecutive case analysis of pretreatment and comparative static radiological parameters following chiropractic adjustments. PMID- 1761967 TI - The physics of spinal manipulation. Part I. The myth of F = ma. PMID- 1761968 TI - Statistical methodology for reliability studies. PMID- 1761969 TI - Q beta and Q gamma components of intramembranous charge movement in frog cut twitch fibers. AB - Intramembranous charge movement was measured in frog cut twitch fibers mounted in a double Vaseline-gap chamber with a TEA.Cl solution at 13-14 degrees C in the central pool. When a fiber was depolarized from a holding potential of -90 mV to a potential near -60 mV, the current from intramembranous charge movement was outward in direction and had an early, rapid component and a late, more slowly developing component, referred to as I beta and I gamma, respectively (1979. J. Physiol. [Lond.]. 289:83-97). When the pulse to -60 mV was preceded by a 100-600 ms pulse to -40 mV, early I beta and late I gamma components were also observed, but in the inward direction. The shape of the Q gamma vs. voltage curve can be estimated with this two-pulse protocol. The first pulse to voltage V allows the amounts of Q beta and Q gamma charge in the active state to change from their respective resting levels, Q beta (-90) and Q gamma (-90), to new steady levels, Q beta (V) and Q gamma (V). A second 100-120-ms pulse, usually to -60 mV, allows the amount of Q beta charge in the active state to change from Q beta (V) to Q beta (-60) but is not sufficiently long for the amount of Q gamma charge to change completely from Q gamma (V) to Q gamma (-60). The difference between the amount of Q gamma charge at the end of the second pulse and Q gamma (-60) is estimated from the OFF charge that is observed on repolarization to -90 mV. The OFF charge vs. voltage data were fitted, with gap corrections, with a Boltzmann distribution function plus a constant. The mean values of V (the potential at which, in the steady state, charge is distributed equally between the resting and active states) and k (the voltage dependence factor) were -59.2 mV (SEM, 1.1 mV) and 1.2 mV (SEM, 0.6 mV), respectively. The one-pulse charge vs. voltage data from the same fibers were fitted with a sum of two Boltzmann functions (1990. J. Gen. Physiol. 96:257-297). The mean values of V and k for the steeply voltage dependent Boltzmann function, which is likely to be associated with the Q gamma component of charge, were -55.3 mV (SEM, 1.3 mV) and 3.3 mV (SEM, 0.6 mV), respectively, similar to the corresponding values obtained with the two-pulse protocol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761970 TI - Voltage-dependent slowing of K channel closing kinetics by Rb+. AB - We have studied the effect of Rb+ on K channel closing kinetics in toadfish pancreatic islet cells. These channels are voltage dependent, activating at voltages positive to -10 mV. The channels also inactivate upon prolonged depolarizations, and the inactivation time course is best fit by the sum of two exponentials. Instantaneous current-voltage relationships show that external Rb+ enters the channel as easily as K+, but carries less current. In the voltage range from -140 to -50 mV, the closing time course of the channels can be fit with a single exponential. When Rb+ is present in the external solution the channels close more slowly. The magnitude of this Rb+ effect is voltage dependent, decreasing at more negative voltages. Similarly, when the internal solution contains Rb+ instead of K+ the closing time constants are increased. The effect of internal Rb+ is also voltage dependent; at voltages positive to -80 mV the closing time constant in internal Rb+ is slower than in K+, whereas at more negative voltages the difference is negligible. With internal Rb+, the relationship between the closing time constant and voltage is best fit with two exponential components, suggesting the presence of two distinct voltage-dependent processes. The results are discussed in terms of a model of the K channel with two internal binding sites, and we conclude that Rb+ produces its effects on channel gating by binding to a site in the pore. PMID- 1761971 TI - Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. AB - Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline. PMID- 1761972 TI - Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system. AB - The ability to move acid/base equivalents across the membrane of identified glial cells was investigated in isolated segmental ganglia of the leech Hirudo medicinalis. The intracellular pH (pHi) of the glial cells was measured with double-barreled, neutral-ligand, ion-sensitive microelectrodes during step changes of the external pH (pHo 7.4-7.0). The rate of intracellular acidification after the decrease in extracellular pH (pHo) was taken as a measure of the rate of acid/base transport across the glial membrane. Taking into account the total intracellular buffering power, the maximum rate of acid/base flux was 0.4 mM/min in CO2/HCO3-free saline, and 3.92 mM/min in the presence of 5% CO2/10 mM HCO-3, suggesting that the acid/base flux was dependent upon HCO3-. The rate of acid influx/base efflux increased both with the external HCO3- concentration and with increasing pHi (and hence HCO3-i). This suggested that the decrease in pHi was due to HCO3- efflux. The rapid decrease of pHi was accompanied by a HCO3- dependent depolarization of the glial membrane from -74 +/- 5 mV (n = 20) to -54 +/- 7 mV (n = 13). Both this depolarization and the rate of intracellular acidification were greatly reduced by the anion exchange inhibitor 4,4 diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 0.3-0.5 mM), but were not affected by the removal of external Cl-. Reduction of the external Na+ concentration to one-tenth normal affected the rate of intracellular acidification only in the presence of CO2/HCO3-: the rate increased within the first 3-5 min after lowering external Na+; after longer exposures in low external Na+ the rate decreased, presumably due to depletion of intracellular Na+. Amiloride (1 mM), which inhibits the Na+-H+ exchange in these cells, had no effect on the rate of intracellular acidification. The intracellular Na activity (aNai) of the glial cells was measured to be 5.2 +/- 1.0 mM (n = 8) in CO2/HCO3 free saline; aNai increased to 7.3 +/- 2.2 mM (n = 8) after the addition of 5% CO2/24 mM HCO3-. Upon a change in pHo to 7.0 in the presence of CO2/HCO3-, aNai decreased by an average of 2 +/- 1.1 mM (n = 5); in CO2/HCO3--free saline external acidification produced a transient increase in aNai. It is concluded that, in the presence of CO2/HCO3-, the rate of intracellular acidification in glial cells is dominated by an outwardly directed, electrogenic Na+-HCO3 cotransport. Neurons, which do not possess this cotransporter, acidify at much lower rates under similar conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761973 TI - Ultrastructural organization of the interstitial subnucleus of the nucleus of the tractus solitarius in the cat: identification of vagal afferents. AB - This electron microscopic study, based on serial section analysis, describes the synaptic organization of the interstitial subnucleus of the nucleus of the solitary tract and identifies the terminals of the vagal primary afferents utilizing degeneration and HRP transport. The interstitial subnucleus contains sparsely scattered cell bodies, numerous dendrites and axon terminals, and bundles of unmyelinated and myelinated axons. The cell bodies which are small in diameter have an organelle poor cytoplasm and a large invaginated nucleus. Axon terminals can be classified into two main types according to their vesicular shape. The first type contains clear, round vesicles and can be further subdivided into two subgroups on the basis of their morphology and the size of their vesicles. In the first subgroup the terminals are small, contain a few mitochondria and their vesicles are densely packed with an homogeneous size. In the second subgroup the terminals which vary from small to large, contain many mitochondria and contain round vesicles which are heterogeneous in size. The second main terminal type consists of axon terminals containing pleomorphic vesicles which are associated with asymmetrical or symmetrical synaptic contacts on dendrites. Axo-axonic contacts are present in the interstitial subnucleus. In general, the presynaptic axon terminals contain pleomorphic vesicles and the postsynaptic elements contain round vesicles of varying size. In some dendrites, identified by the presence of ribosomes, groups of round and/or pleomorphic vesicles are found associated with synaptic contacts. These dendrites are presynaptic to conventional dendrites and postsynaptic to axon terminals. After removal of the nodose ganglion, degenerative alterations are seen only at the caudal and middle levels of the interstitial subnucleus. Degeneration occurs in a few myelinated axons and in axon terminals which usually contain a mixture of small and larger round, clear vesicles. After HRP injection into the vagus nerve, the HRP reaction product is visible in axon terminals filled with clear, round vesicles which are heterogeneous in size. The labelled axon terminals establish single or multiple synaptic contacts. This study demonstrates that terminals of vagal primary afferents consist principally of terminals of the second subgroup. The morphology of these terminals are compared to primary afferents in the brainstem and spinal cord. PMID- 1761974 TI - Patterns of hair cell survival and innervation in the cochlea of the bronx waltzer mouse. AB - A massive loss of inner hair cells typifies the cochleae of Bronx waltzer mutant mice. We have characterized the surviving inner hair cells and their modified innervation by immunocytochemistry using antibodies against neuron-specific enolase, with additional stains for neural cell adhesion molecule and neurofilaments, and by electron microscopy. The surviving inner hair cells vary in size, neuron-specific enolase content and innervation. All neuron-specific enolase-positive cells are innervated by neuron-specific enolase-positive endings. There is apparent correspondence between the neuron-specific enolase immunoreactivity of sensory cells and their innervation. Well-stained cells are richly innervated (and large) while lightly stained cells received fewer nerve endings. Neuron-specific enolase-negative inner hair cells innervated either by neuron-specific enolase-positive or -negative nerve endings are very rare. Ultrastructurally, the surviving inner hair cells vary from those of a normal morphological appearance to underdeveloped or vacuolated. Most of the apparently normal inner hair cells are associated with few nerve endings; instead nerve growth cones are abundant in the adjacent inner spiral sulcus epithelium. Cells forming ribbon synapses with afferent endings are rare. The contingent of efferent endings in the inner spiral bundle depends on the presence of afferent endings. The absence of inner hair cells and the uneven distribution of nerve endings on the surviving cells results in the disruption of normal innervation patterns, especially in the thinning out or discontinuation of the inner spiral bundle and an uneven distribution of tunnel fibres. We infer that the sprouting of nerve endings and their convergence on a selected population of the surviving inner hair cells represents a compensatory regenerative phenomenon in response to the loss and the genetic defect of the remaining inner hair cells. PMID- 1761975 TI - An ultrastructural study of oligodendrocytes in zitter rat: a new animal model for hypomyelination in the CNS. AB - The ultrastructural alterations in oligodendrocytes in the zitter rat--a newly established animal model of CNS hypomyelination--were studied in animals between 3 and 37 weeks of age. Throughout the observation period, the most characteristic alteration was the presence of abnormal structures associated with nuclear membranes and resembling split myelin lamellae. The structures consisted of stacks of membranes continuous with the inner and outer membranes of the nuclear envelope or with plasma membranes. This abnormality was prominent at 3 weeks of age, when initial myelination was probably still occurring. It was decreased transiently at 12 weeks of age and then again increased slightly with advancing age. However, the mean incidence of this abnormality was approximately 5% of the oligodendrocyte nuclei in randomly examined electron micrographs. As the small membranous abnormalities were observed in a few serial sections, the actual incidence is believed to be several times higher than 5%. Such membranous abnormalities were also detected in some mitochondria, in some cisternae of rough endoplasmic reticulum, and in some lysosomes, all at lower incidence rates. Some aberrant or elongated myelin sheath formations, an increased number of radial components and intracytoplasmic inclusions in oligodendrocytes were also observed. These findings suggest that functional abnormalities in membrane biosynthesis including the myelin sheaths and the nuclear membranes in oligodendrocytes are closely related to the hypomyelination in the CNS and may be related to the genetic abnormality in the zitter rat. PMID- 1761976 TI - Motor-unit recruitment in the decerebrate cat: several unit properties are equally good predictors of order. AB - 1. Recruitment order was studied in pairs of motor units of the medial gastrocnemius (MG) muscle of decerebrate cats with the use of dual microelectrode recording from intact ventral root filaments. Excitation was provided by stretch of MG, stretch of synergists [lateral gastrocnemius (LG), plantaris (PL), and soleus (SOL) muscles] or electrical stimulation of the caudal cutaneous sural (CCS) nerve. Motor units were characterized by axonal conduction velocity (CV), tetanic tension (Pmax), twitch contraction time (CT), and fatigue index (FI). 2. Consistent with the recruitment pattern described by others, most often in relation to either CV or Pmax, the first unit of a pair to be recruited by MG stretch was typically the one with the lower CV and Pmax, and the higher FI and CT. The proportion of pairs that agreed in rank order of each property and recruitment order was as follows: for CT, 94%; for CV, 87%; for Pmax, 84%; and for FI, 75%. With a single marginal exception (CT vs. FI), no motor-unit property proved to be significantly better than the others at predicting recruitment (G test; P greater than 0.05). 3. In all 11 tested pairs containing one slow (type S) and one fast (type F) unit, the S was more easily recruited by stretch. Type F units divided into groups with high (type FR), low (type FF), and intermediate (type FInt) values for FI were recruited in order from FR to FInt to FF in 8/11 pairs. Thus our findings were similar to earlier demonstrations that recruitment proceeds in order by type. 4. Stretch of MG synergists usually recruited units in the same order as MG stretch. In two S-S pairs, recruitment order was switched with synergist stretch. 5. Stimulation of the CCS nerve was generally excitatory to the MG units sampled. Most unit pairs were recruited by CCS stimulation in the same order as by MG stretch, but, for 6 of 39 pairs, CCS stimulation switched the order produced by stretch. Thus, whereas sural afferent input can preferentially excite some units over others as suggested by Kanda et al., that effect is not widespread or selective for unit type under these conditions. 6. Assuming that all MG motor units cooperate as a single functional pool in homonymous stretch reflexes, we support others in concluding that a motoneuron's recruitment threshold is not strictly determined by its size. However, our data do not distinguish other schemes that predict recruitment order more accurately than the size principle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761977 TI - Mechanical analysis of heterogenic inhibition between soleus muscle and the pretibial flexors in the cat. AB - 1. The role of proprioceptive pathways linking the direct antagonists soleus (S) and tibialis anterior (TA) muscles in governing the mechanical properties of the ankle joint were studied in the decerebrate cat. Actions of these heterogenic pathways were compared with those between S and extensor digitorum longus (EDL), a muscle that also acts at the metatarsophalangeal joint. These neurally mediated interactions between S and either TA or EDL were studied by applying controlled length changes to the isolated tendons of pairs of these muscles and recording the resulting changes in force. The muscles were activated with the use of electrically evoked crossed-extension reflexes, flexion reflexes, and brain stem stimulation. 2. Heterogenic inhibition from TA or EDL onto S was well developed whether S was initially quiescent or activated by a crossed-extension reflex. The inhibition persisted for the duration of the stretch of TA or EDL. During a crossed-extension reflex, TA did not generate background force, but brief stretch reflexes could be obtained. During flexion reflexes, stretch reflexes in S were usually abolished, and heterogenic inhibition from S to TA was weak or absent. 3. The strength of the heterogenic inhibition onto S was dependent on the initial length and activation level of TA and EDL. Changes in flexor length or activation level per se did not alter the background force or strength of the stretch reflex in S. Even taking into account the variation of strength of inhibition with the initial state of the muscle of origin, the strength of the inhibition was stronger from TA to S than the other way around. 4. The contributions of heterogenic inhibition from TA and EDL to S were independent in the sense that these components summed linearly with each other and with the autogenic reflex in S. In addition, the magnitude of the inhibition from TA to S was proportional to the amplitude of stretch for low to intermediate levels of initial force in S. The inhibition appeared to affect the mechanical responses of S essentially as rapidly as the stretch reflex in this muscle. 5. The heterogenic inhibition from TA to S was reduced or abolished by intravenous injections of strychnine but unaffected by injections of picrotoxin or bicuculline. These results, together with the observation that the inhibition sums linearly with the stretch reflex, suggest that the mechanism of this heterogenic inhibition is glycinergic and postsynaptic and, therefore, may include Ia-disynaptic reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761978 TI - Gustatory neural coding in the monkey cortex: stimulus quality. AB - 1. Extracellular action potentials were recorded from 50 single neurons in the insular-opercular cortex of two alert cynomolgus monkeys during gustatory stimulation of the tongue and palate. 2. Sixteen stimuli, including salts, sugars, acids, alkaloids, monosodium glutamate, and aspartame, were chosen to represent a wide range of taste qualities. Concentrations were selected to elicit a moderate gustatory response, as determined by reference to previous electrophysiological data or to the human psychophysical literature. 3. The cortical region over which taste-evoked activity could be recorded included the frontal operculum and anterior insula, an area of approximately 75 mm3. Taste responsive cells constituted 50 (2.7%) of the 1,863 neurons tested. Nongustatory cells responded to mouth movement (20.7%), somatosensory stimulation of the tongue (9.6%), stimulus approach or anticipation (1.7%), and tongue extension (0.6%). The sensitivities of 64.6% of these cortical neurons could not be identified by our stimulation techniques. 4. Taste cells had low spontaneous activity levels (3.7 +/- 3.0 spikes/s, mean +/- SD) and showed little inhibition. They were moderately broadly tuned, with a mean entropy coefficient of 0.76 +/- 0.17. Excitatory responses were typically not robust. 5. Hierarchical cluster analysis was used to determine whether neurons could be divided into discrete types, as defined by their response profiles to the entire stimulus array. There was an apparent division of response profiles into four general categories, with primary sensitivities to sodium (n = 18), glucose (n = 15), quinine (n = 12), and acid (n = 5). However, these categories were not statistically independent. Therefore the notion of functionally distinct neuron types was not supported by an analysis of the distribution of response profiles. It was the case, however, that neurons in the sodium category could be distinguished from other neurons by their relative specificity. 6. The similarity among the taste qualities represented by this stimulus array was assessed by calculating correlations between the activity profiles they elicited from these 50 neurons. The results generally confirmed expectations derived from human psychophysical studies. In a multidimensional representation of stimulus similarity, there were groups that contained acids, sodium salts, and chemicals that humans label bitter and sweet. 7. The small proportion of insular-opercular neurons that are taste sensitive and the low discharge rates that taste stimuli are able to evoke from them suggest a wider role for this cortical area than just gustatory coding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761979 TI - Functional properties of a slowly inactivating potassium current in guinea pig dorsal lateral geniculate relay neurons. AB - 1. The time- and voltage-dependent properties of a slowly inactivating and depolarization-activated potassium current and the functional consequences of its activation was investigated with current and single-electrode voltage-clamp techniques applied to guinea pig dorsal lateral geniculate neurons maintained as a slice in vitro. 2. In current clamp, application of a step depolarization to near firing threshold resulted in a slowly rising membrane potential that took up to 10 s to reach steady state and firing threshold. In voltage clamp, step depolarization of the membrane potential to values positive to approximately -65 mV resulted in the rapid activation followed by slow inactivation of an outward current. In both cases the sudden depolarization was associated with a large increase in membrane conductance, which gradually lessened in parallel with the slow depolarization in current clamp or with the decrease in outward current in voltage clamp. 3. The time course of inactivation of the outward current, which we refer to as IAs, was well fitted by a two-exponential function with time constants of 96 and 2,255 ms, suggesting the presence of a fast and slow phase of inactivation. The activation threshold for IAs was about -65 to -60 mV, whereas inactivation was incomplete even at -50 mV, suggesting the presence of a substantial "window" current. The time course of removal of inactivation of IAs at -85 to -100 mV was well fitted by a single exponential function with time constant of 91 ms. 4. IAs appears to be mediated by K+. Increasing [K+]o from 2.5 to 10 mM resulted in a reduction in amplitude of IAs, whereas changing from 10 to 2.5 mM [K+]o enhanced this current. Intracellular injection of Cs+ resulted in an abolition of IAs, whereas extracellular application of Ba2+ resulted in a large decrease in the apparent input conductance but relatively little reduction of IAs. 5. Both phases of inactivation of the transient outward current were completely blocked by low doses (100 microM) of 4-aminopyridine (4-AP), but not by extracellular application of Cs+, tetraethylammonium (TEA), tetrodotoxin (TTX), or after block of transmembrane Ca2+ currents. Local application of 4-AP to neurons depolarized to near firing threshold resulted in depolarization associated with a decrease in apparent input conductance, thereby confirming the presence of a window current.4+ this bias against depolarizing inputs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761980 TI - Physiological properties of primary sensory neurons appropriately and inappropriately innervating skin in the adult rat. AB - 1. We have studied the physiology of sensory neurons innervating skin of the rat hindlimb, in three groups of animals: 1) normal animals; 2) animals in which the sural nerve (Sn) had regenerated to its original cutaneous target; and 3) animals in which the gastrocnemius muscle nerve (Gn) had previously been cut and cross anastomosed with the distal stump of the cut Sn so that its axons regenerated to a foreign target, skin. 2. Single-unit recordings were made from 222 afferents in normal, intact animals. They had conduction velocities of 0.5-53.1 m/s. The conduction velocity distribution had distinct peaks at approximately 37.5, 2.5, and 1.25 m/s, presumably corresponding to A alpha beta-, A delta-, and C-fiber populations. Eighty-two percent of the characterized myelinated fibers had low threshold mechanosensitive receptive fields, whereas 16% were high threshold, and only 2% appeared to have no receptive field. The very large majority of low threshold mechanosensitive receptive fields (87%) were rapidly adapting hair follicle afferents. 3. In animals with regenerated Sn, 308 afferents were recorded with conduction velocities of 0.4-58.8 m/s. However, the mean conduction velocity was lower than in control animals (P less than 0.05), and only one peak, at 27.5 m/s, was apparent for myelinated fibers. Eighty-six percent of myelinated fibers were low-threshold mechanosensitive afferents, 8.5% were high-threshold mechanoreceptors (HTMRs), and 5.5% appeared to have no receptive fields. Fewer low-threshold mechanoreceptors (LTMRs; compared with controls) were activated by hair movement (63 vs. 87%). Most of the remainder appeared to be field receptors (which were therefore more commonly observed here than in normal animals). 4. In animals in which the Gn had regenerated to skin, 430 afferents were recorded. These had conduction velocities ranging from 0.6 to 71.4 m/s, and again only one peak was apparent in the myelinated conduction velocity histogram, at approximately 17.5 m/s. Of the myelinated fibers, 79% had low-threshold mechanosensitive receptive fields in skin and 10% high-threshold mechanosensitive receptive fields. The remaining 11% apparently had no receptive field (cf. 5.5% in regenerated Sn). In contrast to normal or regrown sural afferents, only 58% of low-threshold gastrocnemius afferents in skin were rapidly adapting. Of the 42% slowly adapting afferents, many surprisingly responded to hair movement. Thus some gastrocnemius afferents seemed to have retained the adaptation properties characteristic of muscle afferents. Also surprisingly, given that the Gn contains fewer fibers than the Sn, receptive-field areas were not significantly different from regrown or normal sural fibers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761981 TI - Physiological properties of primary sensory neurons appropriately and inappropriately innervating skeletal muscle in adult rats. AB - 1. We have studied the physiology of primary sensory neurons innervating rat hindlimb muscle in the following: 1) normal control animals; 2) animals in which the gastrocnemius nerve (Gn) had regenerated to its original muscle target; and 3) animals in which the cutaneous sural nerve (Sn) had regenerated to a foreign target, muscle. 2. Single-unit recordings were made from 115 afferents in normal, intact animals. They had conduction velocities of 0.8-67.2 m/s, which were distributed with peaks at approximately 1.25, 17.5, and 47.5 m/s. Of the myelinated fibers, 88% had low-threshold mechanosensitive receptive fields and responded to ramp-and-hold stretches of the muscle. The large majority of these fibers (85%) gave slowly adapting responses to ramp-and-hold stretches or direct muscle probing. Stretch-sensitive afferents could be divided (on the basis of their responses to active muscle contraction) into in-parallel or in-series receptors (presumed muscle spindles and Golgi tendon organs, respectively). The in-parallel receptors outnumbered the in-series receptors by approximately 3:2. The 12% of fibers that were insensitive to stretches of the muscle in the physiological range could be divided into roughly equal groups of totally insensitive fibers and high-threshold fibers, which required excessive stretching of the muscle. 3. In the animals with regrown Gn, 94 single fibers with conduction velocities ranging from 11 to 60.6 m/s were studied. The myelinated conduction velocity distribution exhibited only one peak, at approximately 37.5 m/s. Only 67% of the afferents were stretch sensitive (vs. 88% in normal animals), and only about two-thirds of these (vs. 85% in normal animals) gave slowly adapting responses to ramp-and-hold stretches or muscle probing. The incidence of in-series receptors was also increased among regenerated gastrocnemius afferents. The 33% of fibers that were stretch insensitive were mostly unresponsive to even extreme forms of mechanical stimuli. This group presumably represents afferents that failed to make appropriate endings. 4. In the animals with Sn directed to muscle, 460 single afferents were recorded. Their conduction velocities ranged from 0.7 to 67.9 m/s, and the distribution exhibited only a single peak for myelinated fibers at approximately 22.5 m/s, significantly lower than for intact or regrown Gn. Only 41% of the myelinated fibers were stretch sensitive. Nearly all of these (98%) were rapidly adapting to ramp-and hold stretches or muscle probing, in marked contrast to the other groups. Also, unlike other groups, nearly all stretch-sensitive afferents appeared to be in series.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761982 TI - Gustatory responses of neurons in the nucleus of the solitary tract of behaving rats. AB - 1. The activity of 117 single neurons was recorded in the rostral nucleus of the solitary tract (NST) and tested with each of four standard chemical stimuli [sucrose, NaCl, citric acid, and quinine HCl (QHCl)] and distilled water in awake, behaving rats. In 101 of these neurons, at least one sapid stimulus elicited a significant taste response. The mean spontaneous rate of the taste neurons was 4.1 +/- 5.8 (SD) spike/s. The mean response magnitudes were as follows: sucrose, 10.6 +/- 11.7; NaCl, 8.6 +/- 14.6; citric acid, 6.2 +/- 7.8; and QHCl, 2.4 +/- 6.6 spikes/s. 2. On the basis of their largest response, 42 taste neurons were classified as sucrose-best, 25 as NaCl-best, 30 as citric acid best, and 4 as QHCl-best. The mean spontaneous rates for these categories were 4.9 +/- 6.2 for sucrose-best cells, 5.8 +/- 7.4 for NaCl-best, 1.6 +/- 2.0 for citric acid-best, and 5.8 +/- 6.0 spikes/s for QHCl-best. The spontaneous rate of the citric acid-best neurons was significantly lower than that of the other categories. 3. At the standard concentrations, 45 taste cells (44.6%) responded significantly to only one of the gustatory stimuli. Of the 30 acid-best neurons, 23 (76.7%) responded only to citric acid. For sucrose-best cells, specific sensitivity was less common (18/42, 42.9%), and for NaCl-best neurons, it was relatively uncommon (3/25, 12%). One of the 4 QHCl-best neurons was specific. In a concentration series, more than one-half of the 19 specific neurons tested responded to only one chemical at any strength. 4. The mean entropy for the excitatory responses of all gustatory neurons was 0.60. Citric acid-best cells showed the least breadth of responsiveness (0.49), sucrose-best cells were somewhat broader (0.56), but NaCl-best and QHCl-best cells were considerably less selective (0.77 and 0.79, respectively). Inhibition was observed infrequently and never reached the criterion for significance. 5. In the hierarchical cluster analysis, the four largest clusters segregated neurons primarily by best-stimulus category. The major exception to this was a group of sucrose-best neurons that also responded to NaCl and were grouped with the NaCl-best neurons. In a two dimensional space, the specific taste neurons, those that responded to only one of the four standard sapid stimuli, remained in well-separated groups. These specific groups, however, were joined in a ring-like formation by other neurons that responded to more than one of the sapid stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761983 TI - Properties of high-threshold mechanoreceptors in the oral mucosa. I. Responses to dynamic and static pressure. AB - 1. Mechanical response properties of high-threshold mechanoreceptors (HTMs) of the goat oral mucosa were determined by single-unit recording from the palatine and alveolar nerves and from the trigeminal ganglion. The following observations were made. 2. HTMs of the oral mucosa could be separated into two subgroups on the basis of their threshold to mechanical stimulation. Intense pressure receptors (IPRs) comprised a group of A-delta afferents with thresholds of 2-16 g. Mechanonociceptors (MNs) comprised a group of relatively slowly conducting afferents (A-delta and C-fibers) with a higher threshold range (16-300 g). 3. In most instances, MNs lacked pressure-transducing capacity. Tests of reactivity to dynamically or statically applied stimuli revealed that significant functions were rarely fit between MN activity and pressure (4/20 cases). 4. IPRs differed from MNs by their pressure-transducing properties. The afferent response interval was in inverse proportion to the applied pressure. Significant pressure interval functions were fit in 16/20 cases. The relationship between pressure and response interval was best described by power functions. 5. Tests of reactivity to dynamically or statically applied stimuli revealed that IPRs preferred static pressure. Tighter fits and steeper slopes were observed in power functions fit to data generated by statically applied stimuli (mean fitted function, dynamic test: LnISI = -0.97 LnP + 3.4; mean fitted function, static test: LnISI = -1.6 LnP + 4.71). 6. Pressures-frequency thresholds (PFTs), asymptotes (PFAs), and mean response intervals (MRIs) were determined for IPRs from the static test series. The first two values are the pressures that produce the lower and upper limits of response frequency of mucosal HTMs (mean PFT, 1.48 N/mm2; mean PFA, 3.34 N/mm2). The MRI (28 ms) is simply computed from the function. When PFTs and PFAs are combined with activation threshold and power functions, they provide a relatively complete description of the range and form of reactivity of the IPR of the oral mucosa. PMID- 1761984 TI - Properties of high-threshold mechanoreceptors in the goat oral mucosa. II. Dynamic and static reactivity in carrageenan-inflamed mucosa. AB - 1. We have previously described two classes of high-threshold mechanoreceptors (HTMs) of the oral mucosa of the goat. Mechanonociceptors (MNs) had very high thresholds (16-300 g) and were poor transducers of pressure. Intense pressure receptors (IPRs) had thresholds from 2 to 16 g and were good transducers of pressure. After carrageenan inflammation (CI) we observed mechanical sensitization in both classes of HTMs. The characteristics were as follows. 2. Sensitization of MNs was manifested as qualitative shifts in the capacity to encode intense pressure. MNs that were unable to code intensity before CI acquired pressure coding properties after treatment with carrageenan. Qualitative shifts in coding capacity were suggested by the greater proportion of MNs coding in preinflamed (10 of 14) compared with noninflamed tissue (8 of 25 cases). Improved afferent reactivity was directly observed, in additional experiments, in which MNs were characterized in normal tissue before the injection of carrageenan into the mucosa. In five of six cases, either qualitative or quantitative improvements were observed. In control experiments, improved reactivity was observed in one of six cases. 3. Sensitization in IPRs was manifested as both qualitative and quantitative improvement in intensity coding properties. Power functions fit to individual IPRs indicated sensitization for most mucosal afferents after inflammation. Carrageenan induced decreases in the mean response interval, pressure-frequency threshold (PFT), and pressure-frequency asymptote (PFA), and decreases in variability of functions fit to units sampled from preinflamed and noninflamed tissue (n = 23). Experiments were also conducted in which units were characterized before and after carrageenan treatment. In 7 of 10 cases, injection of carrageenan into the oral mucosal led to improved dynamic and/or static reactivity. Injection of vehicle led to changes in reactivity in one of five cases. 4. Carrageenan induced decreases in activation thresholds only when afferent receptive fields fell into restricted tissue zones. Large shifts in activation thresholds were observed for five of five (3 MNs and 2 IPRs) units in the sulcal zone of the incisal papilla (IP). In contrast, activation thresholds increased or remained the same in 11 of 12 units (10 IPRs and 3 MNs) with receptive fields in the medial or ventral tissue zones. Changes in activation threshold evolved slowly after carrageenan injection and required 1-2 h to develop. Rapid changes in activation threshold were also observed in a limited number of cases (3). These threshold shifts were unrelated to carrageenan inflammation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761985 TI - Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons. AB - 1. Voltage-gated K currents were studied in relay neurons (RNs) acutely isolated from somatosensory (VB) thalamus of 7- to 14-day-old rats. In addition to a rapidly activated, transient outward current, IA, depolarizations activated slower K+ currents, which were isolated through the use of appropriate ionic and pharmacological conditions and measured via whole-cell voltage-clamp. 2. At least two slow components of outward current were observed, both of which were sensitive to changes in [K+]o, as expected for K conductances. The first, IK1, had an amplitude that was insensitive to holding potential and a relatively small conductance of 150 pS/pF. It was blocked by submillimolar levels of tetraethylammonium [TEA, 50%-inhibitory concentration (IC50 = 30 microM)] and 4 aminopyridine (4-AP, 40 microM). In the absence of intracellular Ca2+ buffering, the amplitude of IK1 was both larger and dependent on holding potential, as expected for a Ca(2+)-dependent current. Replacement of [Ca2+]o by Co2+ reduced IK1, although the addition of Cd2+ to Ca(2+)-containing solutions had no effect. 3. The second component, IK2, had a normalized conductance of 2.0 nS/pF and was blocked by millimolar concentrations of TEA (IC50 = 4 mM) but not by 4AP. The kinetics of IK2 were analogous to (but much slower than) those of IA in that both currents displayed voltage-dependent activation and voltage-independent inactivation. IK2 was not reduced by the addition of Cd2+ to Ca(2+)-containing solutions or by replacement of Ca2+ by Co2+. 4. IK2 had a more depolarized activation threshold than IA and attained peak amplitude with a latency of approximately 100 ms at room temperature. IK2 decay was nonexponential and could be described as the sum of two components with time constants (tau) near 1 and 10 s. 5. IK2 was one-half steady-state inactivated at a membrane potential of -63 mV, near the normal resting potential for these cells. The slope factor of the Boltzman function describing steady-state inactivation was 13 mV-1, which indicates that IK2 varies in availability across a broad voltage range between 100 and -20 mV. 6. Activation kinetics of IK2 were voltage dependent, with peak latency shifting from 300 to 50 ms in the voltage range -50 to +30 mV. Deinactivation and deactivation were also voltage dependent, in contrast to inactivation, which showed little dependence on membrane potential. Increase in temperature sped the kinetics of IK2, with temperature coefficient (Q10) values near 3 for activation and inactivation. Heating increased the amplitude of IK2 with a Q10 value near 2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761986 TI - Neural control of swimming in Aplysia brasiliana. I. Innervation of parapodial muscle by pedal ganglion motoneurons. AB - 1. Swimming is an oscillatory locomotor behavior in Aplysia accomplished by rhythmic undulating movements of the parapodia, winglike flaps that cover the dorsum of the body. As part of an analysis of the neural basis of this behavior, we have identified and characterized motoneurons in the pedal ganglia that directly innervate parapodial muscle and fire phasically during fictive swimming. 2. Parapodial musculature is organized into at least eight discrete layers. Fibers of adjacent layers are directed orthogonally. 3. Motoneurons were localized to the middle and rostral portions of the dorsal surface of each pedal ganglion by the use of backfill staining and intracellular dyes. These neurons were defined as motoneurons on the basis of additional physiological evidence for peripheral axons and their ability to cause excitatory junction potentials (EJPs; average amplitude, 2-5 mV) in muscle fibers and discrete contractions of parapodial muscles. Muscle fibers are polyneuronally innervated. Fibers had an average resting potential of -79 mV and no over-shooting action potentials. 4. There are probably at least 50 motoneurons. Their average resting potential was 48 mV, and they do not appear to be directly connected synaptically to one another. One identifiable motoneuron is described in detail. It participates in the opener (downstroke) phase of swimming and causes contraction of one of the described muscle layers. 5. Divalent ion concentrations were altered centrally and peripherally during motoneuron activity to demonstrate that the motoneurons directly innervate muscle fibers. Blockage of EJPs by hexamethonium and the presence of specific anticholinesterase staining in parapodial nerves and muscle fibers strongly suggest that many of the motoneurons are cholinergic. 6. Studies of excitation-contraction coupling showed that single or a few spikes in motoneurons rarely cause an EJP. Bursts of motoneuron spikes produced facilitating EJPs. With approximately 10 spikes in a 1-s motoneuron burst, adequate depolarization occurred in muscle fibers to initiate a small, slow contraction. Increased spike frequency led to greater depolarization, because of EJP summation, and larger contractions. Contraction requires depolarization of the muscle above a threshold, beyond which the force of contraction depends on both the duration and degree of depolarization. 7. Although dozens of motoneurons appear to be involved in the complex control of parapodial movements during swimming, preliminary evidence indicates that these neurons are probably not participating directly in the circuitry of the central pattern generator for swimming, which has been shown by others also to reside in the pedal ganglia. PMID- 1761987 TI - Neural control of swimming in Aplysia brasiliana. II. Organization of pedal motoneurons and parapodial motor fields. AB - 1. We have examined the locations and functional properties of a large number of motoneurons in the pedal ganglia of Aplysia brasiliana. These neurons control movement of the parapodia and body during swimming. We have grouped the motoneurons into classes based on several criteria, including the topology of the cells and their axons, the properties of their peripheral motor fields, and their phasic activity during an induced swim motor program. 2. A total of 410 motoneurons were analyzed. There are at least 16 distinguishable motor fields in the parapodia, based on the region affected, direction of contraction, and phase of neuronal activity during fictive swimming. 3. Motoneurons for each motor field tend to appear in the same region of the ganglion in different preparations. 4. Most motoneurons have only ipsilateral effects. About 1% cause contralateral contraction, and they project directly to the contralateral parapodium. 5. Three types of motoneuron are described that cause parapodial expansion. 6. Two other groups of motoneurons were found that innervate either the columellar muscle or longitudinal foot muscles. 7. Almost all motoneurons fired rhythmically during fictive swimming, including those controlling foot and columellar muscle. PMID- 1761988 TI - Kinetics and voltage dependence of A-type currents on neonatal rat sensory neurons. AB - 1. We have characterized three voltage-gated potassium currents on neonatal rat nodose neurons: a rapidly inactivating current (IAf), a slowly inactivating current (IAs), and a noninactivating current (IK). 2. Most neurons expressed all three currents. However, we found that a significant number of neurons had only one of the two A-currents. 3. IAf activates rapidly (tau = 1.0-1.5 ms at -10 mV) and inactivates in 10-30 ms. The activation and steady-state inactivation curves were fit with Boltzmann distributions of V' = -21, k = 12 mV and V' = -73, k = -8 mV, respectively. 4. IAs activates more slowly than IAf (tau = 5.4-9.2 ms at -10 mV) and inactivates with two components (150-300 ms; 1-3 s). The activation and inactivation curves are shifted approximately 20 mV more positive than those of IAf, with Boltzmann coefficients of V' = -2, k = 14 mV and V' = -51, k = -14 mV, respectively. 5. Of the three, IK activates most slowly (tau = 29.4-38.3 ms at 10 mV) and at more positive potentials than IAf or IAs (V' = 16, k = 12 mV). IK does not inactivate over tens of seconds. 6. In addition, we have identified the single channels that underlie IAf and IAs. These two channels, Af and As, have the same single-channel conductance, 22 pS, but different inactivation kinetics. 7. Furthermore, we show that there is an inverse relationship between the appearance of A-currents (IAf and IAs) and the appearance of IK, suggesting that these neurons coordinate the expression of these currents in their membranes. PMID- 1761989 TI - Efferent neurons and suspected interneurons in second somatosensory cortex of the awake rabbit: receptive fields and axonal properties. AB - 1. Receptive-field properties of antidromically identified efferent neurons within the representation of vibrissae and sinus hairs above the mouth were examined in secondary somatosensory cortex (S-2) of fully awake adult rabbits. Efferent neurons studied included callosal neurons (CC neurons, n = 88), ipsilateral corticocortical neurons (C-IC neurons, n = 51) that project to primary somatosensory cortex (S-1), and corticofugal neurons of layer 5 (CF-5 neurons, n = 63) and layer 6 (CF-6 neurons, n = 42) that project to and/or beyond the thalamus. Appropriate collision tests demonstrated that substantial numbers of corticocortical efferent neurons (21 of 113 tested) project an axon to both the corpus callosum and to ipsilateral S-1. 2. Suspected interneurons (SINs, n = 62) were also studied. These neurons were not activated antidromically from any stimulus site but did respond synaptically to electrical stimulation of the ventrobasal (VB) thalamus with a burst of three or more spikes at frequencies of 600 to greater than 900 Hz. Most of these neurons also responded synaptically to stimulation of S-1 and the corpus callosum. The action potentials of these neurons were much shorter (mean, 0.49 ms) than those of efferent neurons (mean, 1.01 ms). 3. CF-5 neurons differed from CC, C-IC, and CF-6 neurons in their spontaneous firing rates, axonal properties, and receptive-field properties. Whereas CF-5 neurons had a mean spontaneous firing rate of 5.7 spikes/s, CC, C IC, and CF-6 neurons all had mean values of less than 1/s. Axonal conduction velocities of CF-5 neurons were much higher (mean, 11.90 m/s) than either CC (mean, 2.63 m/s), C-IC (mean, 0.86 m/s), or CF-6 (mean, 1.73 m/s) neurons. A decrease in antidromic latency (the "supernormal" period), which was dependent on prior impulse activity, was seen in most CC, C-IC, and CF-6 neurons but was minimal or absent in CF-5 neurons of comparable conduction velocity. Although all CF-5 neurons responded to peripheral sensory stimulation, many CC (52%), C-IC (49%), and CF-6 (55%) neurons did not. CC and CF-6 neurons that did not respond to sensory stimulation had significantly lower axonal conduction velocities and spontaneous firing rates than those that responded to such stimulation. Whereas no CC, C-IC, or CF-6 neuron responded synaptically to callosal stimulation, 43% of CF-5 neurons (and 78% of SINs) did so respond. Similar differences in synaptic responsivity to stimulation of S-1 were seen in these populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761990 TI - Modeling the spatiotemporal organization of velocity storage in the vestibuloocular reflex by optokinetic studies. AB - 1. A generalized three-dimensional state space model of visual vestibular interaction was developed. Matrix and dynamical system operators associated with inputs from the semicircular canals, otolith velocity estimator, and the visual system have been incorporated into the model, which focus on their relationship to the velocity storage integrator. 2. A relationship was postulated between the eigenvalues and the direction of the eigenvectors of the system matrix and the orientation of the spatial vertical. It was assumed that the system matrix for a tilted position was a composition of two linear transformations of the system matrix for the upright position. One transformation modifies the eigenvalues of the system matrix, whereas another rotates the eigenvectors of the system matrix. The pitch and roll eigenvectors rotate with the head, whereas the yaw axis eigenvector remains approximately spatially invariant. 3. Based on the three dimensional model, a computational procedure was formulated to identify the eigenvalues and eigenvectors of the system matrix with the use of a modification of the marquardt algorithm. With the use of data obtained from a monkey, it was shown that the three-dimensional behavior of velocity storage cannot be predicted solely in terms of its time constants, i.e., the inverse of its eigenvalues. With the use of the same eigenvalues the data could either be fit or not fit, depending on the eigenvector directions. Therefore, it is necessary to specify eigenvector directions when characterizing velocity storage in three dimensions. 4. Parameters found with the use of the Marquardt algorithm were incorporated into the model. Diagonal matrices in a head coordinate frame were introduced for coupling the visual system to the integrator and to the direct optokinetic pathway. Simulations of optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) were run. The model predicted the behavior of yaw and pitch OKN and OKAN when the animal is upright. It also predicted the cross-coupling in the side down position. The trajectories in velocity space were also accurately simulated. 5. One of the predictions of the model is that when the stimulus direction is along an eigenvector, the trajectory in velocity space is a straight line. Using the "spectral width" of the residuals from a straight line sequence during OKAN, we developed a methodology to estimate how close the OKAN decay was to an eigenvector trajectory. 6. Thus we have developed a model-based approach for studying and interpreting the response characteristics of velocity storage in three dimensions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761991 TI - Spatial orientation of the vestibular system: dependence of optokinetic after nystagmus on gravity. AB - 1. Monkeys received optokinetic stimulation at 60 degrees/s about their yaw (animal vertical) and pitch (animal horizontal) axes, as well as about other head centered axes in the coronal plane. The animals were upright or tilted in right side-down positions with regard to gravity. The stimuli induced horizontal, vertical, and oblique optokinetic nystagmus (OKN). OKN was followed by optokinetic after-nystagmus (OKAN), which was recorded in darkness. 2. When monkeys were tilted, stimulation that generated horizontal or yaw axis eye velocity during OKN induced a vertical or pitch component of slow phase velocity during OKAN. This has been designated as "cross-coupling" of OKAN. Eigenvalues and eigenvectors associated with the system generating OKAN were found as a function of tilt. They were determined by use of the Levenberg-Marquardt algorithm to minimize the mean square error between the output of a model of OKAN and the data. 3. The eigenvector associated with yaw OKAN (yaw axis eigenvector) was maintained close to the spatial vertical regardless of the angle of tilt. The eigenvector associated with pitch OKAN (pitch axis eigenvector) was always aligned with the body axis. The data indicate that velocity storage can be modeled by a piecewise linear system, the structure of which is dependent on gravity and the yaw axis eigenvector, which tends to align with gravity. 4. Yaw axis eigenvectors were also determined by giving optokinetic stimulation about head-centered axes in the coronal plane with the animal in various angles of tilt. A technique using a spectral analysis of residuals was developed to estimate whether yaw and pitch OKAN slow phase velocities decayed concurrently at the same relative rate and over the same time course. The eigenvectors determined by this method were in agreement with those obtained by analyzing OKAN elicited by yaw OKN. 5. During yaw OKN with the animal in tilted positions, the mean vector of the ensuing nystagmus was closer to the body axis than to the spatial vertical. This suggests that there is suppression of the cross-coupled pitch component during OKN. The direction of the stimulus may be utilized to suppress components of velocity storage not coincident with the direction of stimulus motion. 6. There were similarities between the monkey eigenvectors and human perception of the spatial vertical, and the mean of eigenvectors for upward and downward eye velocities overlay human 1-g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1761992 TI - The relationship among leadership preferences, head nurse leader style, and job satisfaction of staff nurses. AB - A better understanding of the effects of the relationships between staff nurses and their leaders is needed if retention of vital resources is to occur in this age of increasing need and decreasing resources in the health care industry. This study investigated the interactions among leadership preferences of staff nurses, the perceived leader behavior of their nurse managers, and their job satisfaction. Although a "match" or "mismatch" relationship was not found, one surprising finding was the high positive relationship between structuring behavior of head nurses and job satisfaction of staff nurses. Implications and recommendations for training nurse managers are offered. PMID- 1761993 TI - Beliefs about mental illness in a culturally diverse nursing student population: implications for education and practice. AB - The effects of a psychiatric nursing curriculum on a culturally diverse nursing student population was investigated using Cohen and Streuning's factor analyzed Opinions About Mental Illness questionnaire. Statistical analysis revealed that the experimental subjects (N = 118) showed change on four out of five selected attitude dimensions. Cultural variables (ethnic group, length of time in the US and political affiliations) corresponded with mental illness attitudes. Length of time in the US had a significant effect on two factors--Authoritarianism and Stereotyping. PMID- 1761994 TI - Military nursing bibliography. PMID- 1761995 TI - Training in injury prevention for health professionals. AB - BACKGROUND: The shortage of health professionals with training in injury epidemiology and control is an obstacle to injury prevention. METHODS: Two two hour workshops in childhood injury epidemiology and control were provided to nurses and physicians in the New York City Department of Health. RESULTS: 101 nurses and 76 physicians received the training. Workshop I test scores rose from 60% to 75%. Workshop II test scores rose from 67% to 88%. DISCUSSION: Training in injury prevention increases knowledge. Future studies will examine the effect of training on practice. PMID- 1761996 TI - Chemical impairment in colleagues: perceptions of Western New York nurses. AB - The purpose of this study was to determine nurses' perceptions about substance abuse in professional colleagues, opinions about strategies for dealing with substance abuse, and knowledge about resources available for dealing with the problem of chemical impairment. Subjects included a convenience sample of 161 nurses from Western New York. Data were gathered by a questionnaire that included "The Perceptions of Nursing Impairment Inventory" and items regarding respondents' background characteristics, suspicions about alcohol and drug abuse in nurse colleagues, and knowledge about and use of peer assistance services available through District I of the New York State Nurses Association. The major outcome of the study was identification of a knowledge deficit on the extent of the substance abuse problem in nursing, ability to recognize an impaired colleague, and awareness of services available. These data substantiate the need for implementing educational programs to increase nurses' basic knowledge of, and sensitivity to, the problem of chemical dependency. PMID- 1761997 TI - Heparin and graduated compression stockings in patients undergoing fractured hip surgery. AB - Despite evidence that effective regimens are available for the prevention of venous thrombosis in fractured hip patients, many centers do not use prophylaxis. In order to evaluate the efficacy and safety of heparin and graduated compression stockings, we conducted a cohort study of 55 consecutive fractures hip patients treated postoperatively with heparin, 5,000 U every 12 h, and graduated compression stockings. The rates of venous thromboembolism and bleeding were compared with an historical cohort from Hamilton. Before discharge, 51 patients underwent bilateral venography. Deep venous thrombosis (DVT) occurred in 10 of the 51 patients (incidence of 20%); three had proximal DVT (incidence of proximal DVT was 6%). DVT was seen in 29 of the 63 control patients (incidence 46%); 19 had proximal DVT (incidence of proximal DVT was 30%). The differences in the rates of DVT and proximal DVT are statistically significant (p less than 0.01). Bleeding occurred in one patient in the treatment group (incidence 2%) and five patients in the control group (incidence 8%). This study confirms that therapy with heparin and graduated compression stockings is effective, inexpensive, and convenient for the prevention of venous thrombosis in fractured hip patients and is associated with a low bleeding risk. PMID- 1761998 TI - The abduction lordotic view of the clavicle: a new technique for radiographic visualization. AB - The abduction lordotic view is a previously unreported radiographic technique for visualization of the clavicle. Use of this technique, a simple office procedure, combined with a standard anteroposterior view allows almost 90 degrees visualization of the clavicle. It is recommended particularly for the assessment of clavicular healing. PMID- 1761999 TI - The posterior Monteggia lesion. AB - Thirteen posterior Monteggia fracture-dislocations in adults were treated surgically at the Massachusetts General Hospital from 1980 to 1988. A characteristic lesion was observed, consisting of a proximal ulna fracture with a triangular or quandrangular fracture at or near the level of the coronoid, a posterior or posterolateral radiocapitellar dislocation, and, in 10 cases, a radial head fracture. Nine patients were women and four were men, with an average age of 56 years. Following reduction of the radiocapitellar dislocation, the ulnar fractures were treated with plates in each case. Seven fractured radial heads were excised, one replaced with a silicone prosthesis, and three treated by open reduction and internal fixation. The 11 surviving patients were observed using the performance index of Broberg and Morrey at an average follow-up time of 38.4 months. The conditions of three were rated excellent, three good, four fair, and one poor. Incomplete reduction of the ulnar fracture with residual posterior radiocapitellar subluxation was observed in four cases, all leading to loss of forearm supination. We believe this lesion to be more common than previously reported. Recognition of its specific anatomic features is essential to achieve a functional outcome. PMID- 1762000 TI - Spinal canal decompression in traumatic thoracolumbar burst fractures: posterior distraction rods versus transpedicular screw fixation. AB - Although the benefit of spinal canal decompression of traumatic thoracolumbar burst fractures is controversial, it remains a desirable procedure, as many reports describe improved neurologic outcome with spinal canal reconstruction. The optimal type of posterior instrumentation for reconstructing the spinal canal is unclear. This study focused on the efficacy of posterior distraction rods versus transpedicular screw fixation implants in decompressing the spinal canal and on the relationship between the amount of canal decompression and subsequent neurologic recovery. A medical records review was conducted to identify all patients surgically treated for traumatic burst fractures of the thoracolumbar spine from January 1, 1987 to June 30, 1989. Sixty-seven patients were selected by this review, and, of these, 30 had had both preoperative and postoperative CT scans. We could find no bias among patients who received both preoperative and postoperative CT scans as compared to those who did not, therefore the 30 patients were considered to be a random sample of the total population of 67. A retrospective study was then conducted on the 30 patients with surgically treated burst fractures--15 treated with posterior distraction rods and 15 treated with AO Fixator Interne transpedicular screw fixation implants. Preoperative and postoperative spinal canal cross-sectional areas were measured directly from the scaled CT scans. The area of most severe compromise was compared with an internal standard defined as the next, caudal, uncompromised spinal level, and the percentage of preoperative and postoperative canal compromise was calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762001 TI - Treatment of posttraumatic reflex sympathetic dystrophy syndrome (RSDS) with intravenous blocks of a mixture of corticosteroid and lidocaine: a retrospective review of 17 consecutive cases. AB - Seventeen consecutive patients with posttraumatic reflex sympathetic dystrophy syndrome (RSDS) were treated with one or more regional i.v. blocks of methylprednisolone sodium succinate and lidocaine HCL after physical therapy and oral medications had failed to produce satisfactory relief of their symptoms. In 12 of these patients the upper extremity was affected, and in five, it was the lower extremity. A fracture of the distal radius was the most frequent predisposing event. The average delay between injury and the manifestation of RSDS was 2.5 months (range 2 days to almost 6 months). The index treatment in all cases started within 3 months of the onset of symptoms. The number of i.v. blocks given ranged from one to four (average 2.4). The side effects and complications were negligible. The treatment, which in most cases was given exclusively on an outpatient basis, was well tolerated by all patients except one. Assessment of 16 of them at 6 months showed that 11 had total or almost total relief of their symptoms. When 15 of the patients were reassessed at an average follow-up of 28 months (range 12-48 months), it was noted that none of the patients with an early satisfactory response experienced recurrence of their symptoms. The condition of the symptomatic patients in the interim had improved overall. Analysis of the cases with an unsatisfactory outcome suggested that the primary reason for failure was inadequate treatment rather than ineffectiveness of the treatment used. It was concluded that this method is simple, safe, and well tolerated and should be regarded as a first choice for posttraumatic RSDS. PMID- 1762002 TI - Three-dimensional load displacement properties of posterior lumbar fixation. AB - Pedicular fixation devices for the posterior treatment of segmental spinal instability are thought to offer enhanced stabilization compared with sublaminar wire systems, while avoiding the immobilization of multiple normal motion segments. We compared the performance of three dissimilar stabilization systems: the Hartshill rectangle, the Acromed/Steffee interpedicular screw and plate, and the Synthes/Dick fixateur interne. Human cadaveric lumbosacral specimens were first tested intact, then after a laminectomy and a facetectomy at the L3/L4 level, and finally after the fixation devices were sequentially attached. Constructs spanning two to four vertebral levels were compared for stabilization of the resected lumbar spine segments. When tested in compression, the Acromed/Steffee system with pedicular screws at L2-L5 allowed significantly less intersegmental distraction than the Synthes/Dick construct with screws at L2 and L5 only, and less than the intact and the destabilized uninstrumented spine. When sagittally rotated, the Acromed/Steffee construct with screws at L2-L5, or at L2 and L5, allowed significantly less distraction than the intact or destabilized segments, and the construct with screws at L2 through L5 allowed less distraction than the Synthes/Dick constructs with screws at L3/L4 or L2/L5. With the exception of the Acromed/Steffee system with screws at four levels, there were no significant differences in distraction allowed between the Synthes/Dick and Acromed/Steffee constructs, or between the multisegment and single segment constructs. There were no significant differences in stiffness across levels L3/L4 with the various implants. Results indicate that the use of posterior spine constructs significantly augment the stability of posterior segmental defects. Pedicular fixation immediately cephalad and caudad to the defect provided stable fixation in this application. PMID- 1762003 TI - Fracture patterns in battered children. AB - We reviewed cases of 75 battered children with fractures over a 2-year period. The average age was 16 months; 57% were boys. There were 154 fractures (2.0 per child); 77% were acute and 23% were old. The most common fracture occurred in the skull (32%) and the most common long bone fracture occurred in the tibia (16%). The most common long bone fracture pattern was transverse (41%); corner fractures accounted for 28% of long bone fractures. An isolated acute fracture was the orthopaedic injury in 65% of the children, whereas multiple fractures in various stages of healing were present in only 13% of children. PMID- 1762004 TI - Anatomical and radiological considerations in compressive bar technique for posterior pelvic disruptions. AB - Sacral bar fixation is a well-recognized technique for the treatment of posteriorly unstable pelvic injuries, particularly sacral fractures. The sacral bars are placed in the iliac crest posterior to the sacrum. We reviewed 103 pelvic computed tomography (CT) scans and three cadaver pelves to measure the iliac crest prominence and its spatial relationship to the lamina of the sacrum. It was found that the best bony purchase for the bars is at the level of the L5 S1 junction. Lower placement of the bar increases the risk of violating the sacral canal and may also decrease the bony purchase of the bars. Some patients have an inadequate iliac crest posteriorly for proper placement; therefore, the pelvic CT scans should always be carefully evaluated preoperatively. The study also includes a description of a technique for percutaneous placement of sacral bars using fluoroscopic guidance. PMID- 1762005 TI - Open reduction and internal fixation of acetabular fractures: heterotopic ossification and other complications of treatment. AB - Open reduction and internal fixation was performed on 50 displaced acetabular fractures in 49 patients by nine different attending surgeons over a 10-year period. At an average follow-up of 38 months, poor results were noted clinically in 38% and radiographically in 40%. The incidence of short- and long-term complications was greater than in other studies. Particularly distressing was the 58% incidence of heterotopic ossification (HO). Twenty-four percent had grade III or IV; five hips were autofused and the remainder had 40-60% loss of motion. There was no correlation of HO with age, sex, fracture type, degree of comminution, associated femoral head fracture or dislocation, delay to surgery, or operative time. However, 26 of 28 patients who had a trochanteric osteotomy as part of the operative exposure developed HO. Other complications included wound infection (12%), avascular necrosis of the femoral head (10%), nerve palsy (8%), and deep vein thrombosis/pulmonary embolism (8%). The data suggest formulation of specific treatment protocols, an awareness of surgical risks, and that staff specialization may reduce complications and improve outcome. Avoiding a trochanteric osteotomy at surgery and using prophylactic postoperative irradiation or indomethacin are suggested to reduce HO. PMID- 1762006 TI - Pertrochanteric fractures in the elderly: are there indications for primary prosthetic replacement? AB - During a 10-year period (1978-1988), 565 patients, aged greater than or equal to 70 years, who sustained a fresh pertrochanteric fracture, were treated in the Department of Traumatology at the University Hospitals of Leuven, Belgium. Three hundred eighty-eight fractures were complex and unstable, according to the Evans Jensen system and the AO system. Special attention was given to the 324 cases of type IC and ID in Evans' system, type A2 in the AO system. The method of treatment changed greatly during the period of study. All patients were followed prospectively during 1 year. Our study showed that for these unstable fractures, fixation with an angled plate or Ender nails should be forsaken. The overall results of the compression hip screw treatment were good (reoperation rate 2%, good functional results in 64%), but as this treatment has a risk for serious collapse and pain in about 80% of all type ID fractures, one could suggest treating these complex multifragment fractures primarily with an endoprosthesis. This treatment need no longer be considered severe intervention, as the danger of mechanical complications is minimal (less than 1%). PMID- 1762007 TI - Treatment of intertrochanteric fractures: comparison of Ender nails and sliding screw plates. AB - The results of two fixation devices for the treatment of intertrochanteric fractures were compared in 220 patients--163 women and 57 men with a mean age of 81 +/- 10 years. One hundred and one patients were randomized to Ender nailing and 119 to fixation with a sliding screw plate (SSP). The two treatment groups were equal with respect to important preinjury variables. The two methods did not differ in operating time or perioperative blood loss. The proportions of good reduction of the fractures and of good positioning of the internal fixation devices were equal in the two groups. But the complication rate and the reoperation rate were more than twice as high in the Ender group than in the SSP group. The outcome at 1-year follow-up was approximately equal in the two groups. PMID- 1762008 TI - Subtrochanteric femur fractures: a comparison of the Zickel nail, 95 degrees blade plate, and interlocking nail. AB - Seventy-nine nonconsecutive patients with subtrochanteric femur fractures were divided into three groups based on the method of fracture fixation. Group I consisted of 21 patients treated with a Zickel nail, Group II comprised 25 patients treated with a 95 degrees blade plate, and Group III included 33 patients treated with an interlocking nail. All patients in Group I and Group II had open reduction and internal fixation of their fractures. Ninety-four percent of the patients in Group III were treated by closed intramedullary nailing. The average operating times for Groups I, II, and III were 212, 272, and 181 min, respectively, while blood loss averaged 900, 1,500, and 600 ml for each group, respectively. Group I had one infection, ten malunions, and one nonunion. Group II had one infection, six malunions, and two nonunions. Group III had no infections, two malunions, and one nonunion. We conclude that closed interlocking nailing is the treatment of choice for acute nonpathologic subtrochanteric femur fractures in adults. There is decreased blood loss, reduced operating time, and fewer complications than with either the Zickel nail or the 95 degrees blade plate regardless of the fracture pattern or the degree of fracture comminution. PMID- 1762009 TI - The effect of autogenous bone graft application on wound contamination. AB - A rat model was created in which contaminated wounds were closed in either the presence or absence of autogenous bone graft. The recipients of bone graft were divided into two groups--one receiving autogenous cancellous bone, the other receiving nonviable autogenous autoclaved cortical bone. Quantitative bacterial cultures were collected both at the time of wound closure and 2 weeks after closure. A significantly increased level of soft-tissue contamination was associated with wound closure in the presence of either type of bone graft, indicating an overall adverse effect on soft tissues. A critical level existed such that at initial bacterial contamination levels greater than 10(4) organisms/g tissue, final contamination levels were significantly elevated. With initial contamination levels less than 10(4) organisms/g tissue, however, final bacterial contamination levels were not significantly different. These results may help explain the different rates of infection that have been reported when delayed primary closure of open fractures is done in conjunction with autogenous bone graft. PMID- 1762010 TI - Harvesting of autogenous cancellous bone graft from the proximal tibial metaphysis. A review of 230 cases. AB - A study was undertaken to review the results of donor site morbidity of cancellous bone grafts obtained from the proximal tibial metaphysis. Two hundred six patients who underwent 230 proximal tibial bone graft harvestings were reviewed. Patients with lower-extremity fractures or nonunions who required cancellous bone grafts and would be non-weight-bearing for at least 6 weeks were selected to undergo the procedure. Minimum length of follow-up was 4 months, with an average length of follow up of 20.4 months. The proximal tibial metaphysis was found to supply an adequate amount of graft for all procedures involved, with a complication rate related to graft donor site of 1.3%. This compares favorably to a previously published report on bone grafts taken primarily from the iliac crest. The postoperative appearance of the proximal tibia may be permanently altered by the procedure, but weight-bearing after 6 weeks appears safe. The proximal tibial metaphysis is a useful site for obtaining cancellous bone graft and is associated with a low morbidity. PMID- 1762011 TI - Type III fractures of the tibial tubercle in adolescents. AB - Fifteen patients with Type III avulsion fractures of the tibial tubercle treated surgically were reviewed at an average of 9.6 years after injury. Six patients had a history of Osgood-Schlatter disease, and two patients had Type I osteogenesis imperfecta. Associated injuries to the meniscus were found and repaired in three patients. Two of these patients had also avulsed the origin of the tibialis anterior muscle, leading to a compartment syndrome in one. All but one fracture healed. There was one refracture. Five patients developed bursitis over prominent screw heads, which required screw removal. All but two patients were asymptomatic and participated in sports. A full range of knee motion without instability was present in all patients. Thigh and calf circumferences were equal to the opposite side. Radiographs showed normal knee joints in all but one asymptomatic patient, who showed signs of an early arthrosis. No patient developed angular or recurvatum deformities. However, a leg-length discrepancy of 1.0-1.8 cm was noted in four patients (two overgrowth, two undergrowth). PMID- 1762012 TI - An investigation of the contribution of the extraosseous tissues to the diaphyseal fracture callus using a rabbit tibial fracture model. AB - The contribution of the extraosseous tissues to diaphyseal fracture healing was investigated using a new fracture model. A transverse osteotomy of the tibial diaphysis of 18 New Zealand White rabbits was reamed and nailed, and a 2-cm length of the periosteum was excised from either side of the osteotomy. Healing was studied by radiography and by haematoxylin/eosin histology at intervals over 2 weeks. None of the osteotomies had united at the end of the observation period. Within days, cellular activity was observed in the remnant of the periosteum, which subsequently resulted in cartilage and bone formation. The repair tissue derived from the periosteum advanced in the direction of the osteotomy site. The extraosseous tissues did not appear to contribute significantly to the fracture callus. PMID- 1762013 TI - Induction and prevention of pin loosening in external fixation: an in vivo study on sheep tibiae. AB - In external fixation of fractures, pin loosening is a major concern. Preloading the pins is generally done to ensure their stability within the bone cortex. The effect of radial preload and bending preload in reducing resorption at the pin/bone interface was tested. Schanz screws were fixed to live sheep tibiae using a pneumatically operated external fixator frame. Evaluation was based on radiological observation and fluorochrome histology using sequential labels. Though not completely absent, bone resorption was minimal in the radial preload group, compared with the two other groups. More important, the bone-to-pin contact surface in the radial preload group was found to be almost intact after 5 weeks. In this study, radial preload appears to be superior to bending preload in terms of minimizing the problems of pin loosening. PMID- 1762014 TI - External fixation of the sternum for thoracic trauma. AB - A flail chest with a manubriosternal separation in a man with multiple injuries was treated with an external fixator applied to the sternum and the manubrium. Pain and ventilatory function were improved, permitting immediate postoperative extubation and prompt patient mobilization. The external fixator was removed after fracture union at 2 months. One year after injury, the patient's pulmonary function was normal. External fixation is an alternative to other methods of sternal fracture stabilization. PMID- 1762015 TI - Unilateral lumbosacral facet joint dislocation associated with vertical shear sacral fracture. AB - An 18-year-old woman involved in a motor vehicle accident sustained a vertical shear fracture of the sacrum accompanied by unilateral dislocation of the L5-S1 joint. Evaluation of the patient's injuries was defined by computed axial tomography. Through a posterior midline incision, open reductions of the dislocated L5-S1 joint and of the sacral fracture were performed. Reduction was followed by anterior stabilization of the symphysis pubis. The patient remained neurologically intact after surgery. PMID- 1762016 TI - Fixation of a fracture of the femoral head with preservation of remaining soft tissue attachments. AB - Residual soft-tissue attachments may provide a blood supply to femoral head fragments after fractures associated with traumatic dislocation of the hip. Screw fixation of these fractures without sacrifice of the attachments can prove to be difficult. A case is presented using a method of fixation--not, to my knowledge, previously reported--that preserves these attachments and facilitates subsequent removal of metalware. PMID- 1762017 TI - Technique for treatment of a bent Russell-Taylor femoral nail. AB - A case is presented in which a 14-mm Russell-Taylor intramedullary nail, placed to secure a right femoral shaft fracture, was deformed 22 months postoperatively by subsequent trauma. The nail was straightened in situ, removed, and replaced with a larger nail. The femur subsequently healed without complication. PMID- 1762018 TI - Migration of a screw from a plated femur into the knee joint 22 years postoperatively. PMID- 1762019 TI - Open tibia fracture caused by femoral shaft fragment. AB - Open tibia fractures and open femoral shaft fractures are commonplace in today's motorized society. We report a unique combination of injuries sustained by two patients treated at our institution. PMID- 1762020 TI - Orofacial functions in patients with congenital and acquired maxillary defects: a fluoroscopic study. AB - By means of videofluoroscopic recordings, chewing, swallowing and speech were monitored in nine patients with congenital and acquired maxillary defects. All of them were rehabilitated with a maxillary obturator prosthesis. The defective region was seldom used for chewing. No leakage between the obturator and surrounding tissue was observed, either for solids or for liquids. All of the prosthetic reconstructions were surprisingly stable during function. In the phonetic analysis, speech production was judged to be restored almost to normal. Videofluoroscopy may be valuable as a complement to other functional diagnostic procedures, and for the evaluation and improvement of rehabilitation with an obturator prosthesis. PMID- 1762021 TI - The relationship between failure and design in conventional bridgework from general dental practice. AB - A total of 142 failed bridges constructed in general dental practice were assessed for design factors that might relate to failure. The overall mean age of the bridges at failure was 6.2 years; anterior and complex bridgework had a mean age of about 5 years, compared with 7.5 years for posterior bridges. The lifespan of the bridgework was significantly correlated with the number of retainers but not with the number of units. Bridges with one or two retainers had an average lifespan of just over 7 years, whilst those with three or more retainers had been in service for, on average, only 4 years. The practical difficulties of constructing multi-abutment bridgework could account for this difference. One hundred and ninety-one of the 346 retainers were porcelain bonded to semi non precious metal crowns, and had a mean lifespan of 3.7 years, whilst those that were gold based lasted at least twice as long. Post crowns as retainers survived on average for 6.2 years. PMID- 1762022 TI - Mandibular manipulation of anterior disc displacement without reduction. AB - The history and clinical symptoms of anterior temporomandibular joint disc displacement without reduction are characteristic, and include limitation of mandibular movement and mandibular deviation on opening of the mouth. Twelve consecutive patients attending a clinic with such symptoms were treated by mandibular manipulation. An immediate increase in the range of mandibular movement was obtained for all patients, with a mean increase in interincisal opening of 8 mm. The method of manipulation is described, and the implications of the results for the treatment of TMJ patients are discussed. PMID- 1762023 TI - Tooth enamel softening with a cola type drink and rehardening with hard cheese or stimulated saliva in situ. AB - The in-situ remineralization effect of hard cheese was compared with that of saliva on tooth enamel in man. The intra-oral test of softening enamel surfaces by a cola type drink followed by rehardening by chewing hard cheese and/or parafilm was assessed by microhardness and SEM measurements. Cheese consumption significantly increased the enamel hardness, whereas stimulated saliva did not have this effect. The remineralizing effects are presumably due to uptake of calcium and phosphate salts by the surface enamel. Morphologically, the enamel surfaces did not return to their original state. PMID- 1762024 TI - Effects of phosphoric acid and tannic acid on dentine collagen. AB - We examined the effects of phosphoric acid, the most common enamel etchant in composite resin therapy, on dentine collagen. Dentine collagen pretreated with 7M phosphoric acid was shown to be more susceptible to trypsin digestion than untreated collagen. This susceptibility increased with increasing duration of exposure to the acid. The results indicate that phosphoric acid induces a conformational change in dentine collagen (denaturation or perturbation) similar to that observed with 0.39 M HCl, which has a similar pH value (0.65). However, phosphoric acid-pretreated dentine collagen, when treated with tannic acid for 2 h, became as resistant to tryptic digestion as intact dentine collagen. The present results suggest that tannic acid may work as a dentine conditioner in composite resin therapy, in view of the fact that phosphoric acid etchant is applied, either deliberately or inadvertently, to dentine, and would thus induce denaturation or perturbation of collagen. PMID- 1762025 TI - In-vitro study to compare the efficacy of N-monochloro-D,L-2-aminobutyrate (NMAB, GK-101E) and water in caries removal. AB - The present in-vitro study was designed to investigate the chemical efficacy of N monochloro-D,L,-2-aminobutyrate (NMAB, GK 101E) in removing carious material under clinically relevant conditions, using objective methods of measurement. Assuming that the chemical effectiveness of water in caries removal is minimal, a comparison of the efficacy of GK-101E with that of water was made. The force required to achieve complete caries removal from symmetrically separated carious lesions was determined with the Caridex system, modified by a force gauge. One lesion half was treated with GK-101E, while the corresponding half was treated with water. Thus a difference in the chemical potential of the fluids in softening carious material should lead to a difference in the force required to remove equal quantities of caries. Statistical analysis of the findings of the present study revealed no significant difference between GK-101E and water, with regard to both the force and the number of excavation strokes and the time needed for caries removal. It is concluded that, under the given test conditions, the removal of carious dentine is not significantly enhanced by the chemical action of GK-101E. PMID- 1762026 TI - Orthognathic diagnosis and treatment planning: a cephalometric approach. AB - Cephalometric analyses have long been important diagnostic tools for the orthodontic specialist. Such analyses, as they pertain to adult skeletal problems and their consequent therapy, should also be a valuable adjunct for various dental specialties, e.g. the oral surgical clinician. However, because of the complexity of most analyses, it is difficult to glean the important values needed for most orthognathic cases. In this article an analysis is presented to aid the clinician in surgical diagnosis and treatment planning. PMID- 1762027 TI - Defects in automixed addition silicone elastomers prepared by putty-wash impression technique. AB - Voids presenting in impressions of five automixed addition silicone elastomers were investigated. Impressions were prepared with the putty-light body impression technique on stainless-steel cylinders with acrylic spacers. The number of voids was counted at a predetermined site on three separate days using a stereomicroscope at x7 magnification. Impression specimens of a hand-mixed addition silicone, and from hand-mixing of the automixed materials, were made for comparison. Express gave a significantly higher number of voids than other automixed materials, with President Jet having the lowest void count. Automixed materials generally produced impressions with significantly fewer voids than the hand-mixed material. Automixing was effective in reducing void defects in elastomeric impressions. PMID- 1762028 TI - Activity index and isometric contraction velocity of human jaw muscles. AB - To determine the relative contribution of the masseter and anterior temporalis muscles to global isometric bite force, activity indices were constructed on the basis of the peak mean voltage (microV) and the integrated voltage (microV.s) of bipolar surface electromyograms obtained during brief maximum voluntary teeth clenching (MVC). The index that was based on integrated myoelectrical activity showed that the masseter muscle contributed the major part of the isometric MVC force. The index that was based on instantaneous peak myoelectrical activity also showed that activity in the masseter muscle predominated over that in the anterior temporalis muscle. In addition, the latter index showed a negative linear association with the initial (0-50% MVC) isometric contraction velocities of the masseter and anterior temporalis muscles. Both indices appear to be promising clinical diagnostic tools. PMID- 1762029 TI - Palpation as a method for evaluating occlusal discrepancies. AB - In this study, 30 dentists were surveyed about their methods of palpating teeth for the evaluation of premature contacts. Thirty-eight dentists were then tested to determine their ability to discriminate degrees of prematurity using each of two different methods of palpation. The degree of digital pressure used by each dentist during palpation was also measured. The majority of dentists chose the same method for palpation: a single forefinger overlaying the facial surfaces of the central incisors being evaluated. In the discrimination test, the majority of dentists were able to identify reliably occlusal interference of greater than or equal to 50 microns regardless of the palpation method used. PMID- 1762030 TI - Prevalence of craniomandibular disorders in adults of Ilala District, Dar-es Salaam, Tanzania. AB - The prevalence and distribution of signs and symptoms of craniomandibular disorders (CMD) were studied in a random sample of 100 adult Tanzanians. The associations between subjective and objective findings were analysed. Signs and symptoms of CMD were assessed by interview and clinical examination. Twenty-six per cent of subjects reported at least one symptom, and in 40% at least one clinical sign was present. No significant differences were observed between the sexes. Tenderness of the lateral pterygoid area and crepitation of the temporomandibular joint increased significantly with age. Several significant associations between subjective and objective findings were observed. The distribution of the signs and symptoms of CMD in Tanzanians was not dissimilar to that observed in the developed countries. The prevalence was not high by comparison, but sufficient to lend credence to the general view that CMD is a universal problem. PMID- 1762031 TI - Oncogenes and anti-oncogenes; the molecular basis of tumour behaviour. PMID- 1762032 TI - Apoptosis in cultured rat hepatocytes: the effects of tumour necrosis factor alpha and interferon gamma. AB - We investigated the cytotoxic effects of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on rat hepatocytes in culture. Under phase contrast microscopy, we found a small number of dying hepatocytes in control cultures, each having been transformed into a cluster of small spheres. Under transmission electron microscopy, these cells showed the characteristics of apoptosis. TNF alpha and a combination of TNF alpha and IFN gamma exerted a cytotoxic effect, whereas IFN gamma showed no significant cytotoxicity when assessed by neutral red assay and by measuring LDH activity in culture medium. Under phase contrast microscopy, the number of apoptotic cells increased with the addition of either TNF alpha or IFN gamma, and markedly with the addition of both. DNA extracted from apoptotic cells cultured with TNF alpha and IFN gamma was fragmented, and a set of bands of the '200 bp ladder', which is characteristic of the DNA of apoptotic cells, was observed in agarose gel electrophoresis. These findings indicate that cultured hepatocytes die from apoptosis. TNF alpha killed cultured rat hepatocytes by increasing apoptosis, and this effect was potentiated by the addition of IFN gamma, which by itself was also weakly cytotoxic. PMID- 1762033 TI - Recovery from hepatic necrosis following acute portal vein embolism with special reference to reconstruction of occluded vessels. AB - We examined the morphological and haemodynamic changes in the livers of rats following acute obstruction of portal vein branches by the injection of agar into the portal vein. Histological and angiographic examinations of the liver were performed after measurements of portal vein pressure in vivo and portal vascular resistance by an isolated liver perfusion method. Portal vein embolism induced hepatic necrosis in the centrilobular and midzonal areas, which was rapidly resorbed and replaced by regenerated liver cells leaving no trace. This recovery from hepatic necrosis was closely related to recanalization of obstructed portal vein branches, which led to falls in both the elevated portal vein pressure and the increased portal vascular resistance following embolization. PMID- 1762034 TI - An assessment of MAC 387 antibody as a diagnostically useful marker of L1 epithelial antigen expression by lung tumours. PMID- 1762035 TI - Measurement of Breslow depth. PMID- 1762036 TI - Publishing clinical papers. PMID- 1762037 TI - Biliary atresia. AB - Care of the child with biliary atresia is a challenge for pediatric nurses. The cause of the disease is not known, and new diagnostic tests and treatment options are continually being developed. This article addresses fundamental issues specific to the care of children with biliary atresia. In order to understand the clinical manifestations and the treatment rationale, pathophysiology and theories of etiology are discussed. Nursing care of the child and issues regarding the teaching and support of the family system are addressed, with suggestions for independent reading. PMID- 1762038 TI - The consequence of maternal depression for early mother-infant interaction: a nursing issue. AB - Adequate mother-infant interaction during the first year of a child's life is critical for secure attachment and basic to development of the child's lifelong emotional competence. Maternal depression can have decidedly deleterious effects on this delicate process. This article will explore the consequences that maternal depression can have for early maternal-child interaction. It will offer the nurse clinician specific recommendations for assessment and intervention to support the normalization of depressed mothers' parenting. PMID- 1762039 TI - Achieving excellence in nursing. AB - The critical shortage of nurses has placed a heavy burden on managers. Because they are responsible for ensuring that pediatric staff members maintain high professional standards, the promotion excellence within the staff remains imperative; it is essential that managers assist themselves and others to strive for excellence. How do you strive for excellence? A commitment to excellence requires a lifelong commitment to nursing, research, learning, scholarship, and personal balance and well-being. Pursuit of excellence in nursing is difficult, especially in a society marked by its satisfaction with mediocrity. Yet by this pursuit, not only will the nurse benefit, but so will the staff, the children, and maternal-child nursing. PMID- 1762040 TI - Conceptions of health and health behaviors of preschool children. AB - A modified version of Flaherty's (1986) Preschool Health Picture Interview was administered to 30 preschool children to explore their conceptions of health and health behaviors. Health was conceptualized as a positive feeling state and the ability to participate in desired activities. Brushing teeth and eating were the highest ranked health-promotion behaviors. Behaviors harmful to health were explained in terms of immediate physical consequences. Responses to all questions were predominantly behavioral. A t test showed that the mean number of moral responses given by boys to all questions was significantly greater (p = 0.04) than the mean number given by girls although no significant differences between boys' and girls' responses were found for any subgroup of questions. PMID- 1762041 TI - Pediatric staff nurses' reactions to job characteristics. PMID- 1762042 TI - Team research: development of "we" in nursing research. AB - Team (tem) n. 1. a. Two or more draft animals harnessed to a vehicle or farm implement, b. A vehicle along with the animal or animals harnessed to it. 2. A group of animals exhibited or performing together. 3. A group of players on the same side in a game. 4. Any group organized to work together. PMID- 1762043 TI - Prescriptive authority for nurse practitioners: a strategy for improving access to child health care. PMID- 1762044 TI - The button: replacement gastrostomy device. PMID- 1762045 TI - Battered child syndrome: educating the pediatric nurse. PMID- 1762046 TI - Pediatric nursing in Japan. PMID- 1762047 TI - "Management of the infant with respiratory syncytial virus". PMID- 1762048 TI - Nursing responsibility in the diagnosis, care, and treatment of the child with gastroesophageal reflux. AB - Gastroesophageal reflux (GER) has been known to occur in infants but was thought to be normal. As a result of increased recognition of GER and a clear documentation of GER with extended (18 to 24 hour) esophageal pH monitoring, several severe complications of GER in children have become apparent. An immature cardiorespiratory system is susceptible to some complications of GER such as apnea, choking, recurrent cough or wheezing, and recurrent aspiration pneumonia. Noncardiorespiratory complications include weight loss, esophagitis, anemia, irritability, posturing, malnutrition, and developmental delays. Nursing assessment contributes to a complete clinical picture and the subsequent treatment choice of the physician. To form an accurate assessment of the child with suspected GER, the nurse must be aware of the symptoms and complications of this condition and must precisely execute diagnostic studies, particularly extended esophageal pH monitoring. Nursing responsibilities also include providing a safe yet stimulating environment for the child, teaching parents to participate in the child's care, supporting parents through hospitalization, and preparing both the parents and child for discharge and follow-up care at home. PMID- 1762049 TI - [Research and development of pravastatin]. AB - The attempts to find a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which catalyzes the rate limiting step of cholesterol biosynthesis were started from 1971. The first potent inhibitor, ML-236B (compactin), was found from the culture broth of Penicillium citrinum. Among many derivatives of ML-236B, pravastatin sodium (hereafter refer to pravastatin) was finally selected because of its potency and tissue selectivity. Since pravastatin has a hydroxyl group at 6 beta position in the skeleton of decaline of ML-236B, the microbial hydroxylation was adopted for the production of pravastatin. Streptomyces carbophilus was finally chosen as a potent converter with the formation of a lesser amount of by-products. For the sake of industrial production of pravastatin, many devices and improvements were performed for selecting high potent strains and for culturing conditions both with ML-236B and pravastatin. Pravastatin strongly inhibited the sterol synthesis in freshly isolated rat hepatocytes, but only weakly inhibited in the cells from nonhepatic tissues. This selective inhibition of pravastatin in sterol synthesis was further confirmed by ex vivo and in vivo experiments by using rats and mice. Pravastatin markedly reduced serum cholesterol levels in dogs, monkeys and rabbits, including Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Pravastatin showed the preventive effect on the development of coronary atherosclerosis and xanthoma in young WHHL rabbits in consequence of maintaining the serum cholesterol levels low. In the clinical trials, pravastatin significantly reduced serum cholesterol and low density lipoprotein cholesterol levels, whereas inversely increased high density lipoprotein cholesterol levels. PMID- 1762050 TI - [Mammalian cellular phospholipases A2 and their physiological roles]. AB - Phospholipase A2 hydrolyzes the ester linkage at sn-2 of glycerophospholipids and is thought to function as a key enzyme in generation of variety of bioactive mediators, such as prostaglandins and platelet-activating factor. In the present review, recent studies on two kinds of cellular phospholipases A2, 14 kDa group II phospholipase A2 and arachidonate-preferentially hydrolyzing phospholipase A2, will be summarized. PMID- 1762051 TI - [Monoamine oxidase inhibitory effects of pentanthrene type heterocyclic compounds]. AB - Pentanthrene type heterocyclic compounds, which contain oxazole, isoxazole, oxadiazole, thiazole, isothiazole, thiadiazole or pyrrole ring as C-ring, and naphthalene, quinoline, isoquinoline or quinoxaline ring as A.B-ring, were prepared, and their monoamine oxidase (MAO) inhibitory activities were examined. As expected from our previous investigation on the structure-activity relationship of this series, most of them showed strong inhibitory potency to both MAO-A and MAO-B. However, a few indicated highly selective inhibition for either of MAO subtypes. PMID- 1762052 TI - [Physiologically active compounds in the extracts from tochukaso and cultured mycelia of Cordyceps and Isaria]. AB - Tochukaso is a Chinese traditional medicine composed of a fruit body of Cordyceps sinensis and its parasitic host larva. Tochukaso (C. sinensis) and the cultured mycelia of five species of Cordyceps and four species of Isaria were each extracted with hot water and examined for the inotropic effect on guinea-pig right atrium in vitro system. The extracts from C. militaris and I. felina showed a negative inotropic effect to approximately the same extent as that from Tochukaso. These three extracts also showed inhibitory action on twitch response of guinea-pig ileum and aggregation of human blood platelet. It is suggested that these activities are ascribed to the combination of adenosine, 5'-adenosine monophosphate and several other nucleic acid-related compounds, all of which have been shown to be present in the extracts. PMID- 1762053 TI - [Study on fluidized melt-granulation. I. Examination of the factors on the granulation]. AB - The purpose of this study is to develop a new granulation method by using a fluidized-bed granulator, which requires a nucleus with a low melting point as a binder. This method was named as fluidized melt-granulation. The technique is very simple and useful. In this paper, the granulation mechanism and the effect of the physico-chemical properties of raw materials on the growth of the granules were investigated. The results were as follows: (1) The mixture of the nucleus and the other powder particles was heated up to the melting point of the nucleus by hot inlet air, immediately resulting in the generation of the adhesion of the powders on the melted nucleus. The granules grew as the melted material immersed into the void space among the adhered particles. (2) The lower the viscosity of the melted nucleus was, the faster the granule grew. (3) The shape and the size of the nucleus affected those of the products. (4) The optimum mixing ratio between the nucleus and the granulated materials existed and it depended on the ratio between the surface areas of these materials. PMID- 1762054 TI - [Studies on the metabolic fate of gomisin A (TJN-101). I. Absorption in rats]. AB - Gomisin A (TJN-101) is one of the lignan components isolated from Schisandra Fruits and expected to have some efficacies in clinical treatment of hepatitis. The serum concentrations of TJN-101 and Met. B, which was identified as a demethylenated substance and one of the major metabolites of TJN-101 in rats, were investigated. After intravenous administration at doses of 1.6, 4.0 and 10 mg/kg of body weight, the serum concentration of TJN-101 decreased biphasically, and the terminal elimination half-life at each dose was about 70 min. Dose dependency was observed for the area under the concentration-time curve (AUC). On the other hand, the serum concentration of TJN-101 increased rapidly and reached maximum within 15 to 30 min when administered orally. This result was supported by the in situ roop method. The Cmax and the AUC values were not exactly dose dependent, but the values increased with a dose-up of TJN-101. The biotransformation of TJN-101 to Met. B, was very rapid in both intravenous and oral administrations. The AUC value of Met. B after oral administration of TJN 101 at a dose of 1.6 mg/kg was relatively larger than any other dosages. It suggested that TJN-101 was extensively underwent the first pass effect in rats. More than 80% of TJN-101 was bound with rat serum protein in vitro and in vivo. Therefore, it seems to be necessary to pay attention when it was administered concurrently with high protein binding drugs. PMID- 1762055 TI - [Studies on the metabolic fate of gomisin A (TJN-101). II. Absorption and excretion in CCl4 treated rats]. AB - The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p less than 0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762056 TI - [High performance liquid chromatographic analysis of typical ultraviolet absorbers in cosmetic products]. AB - Typical 11 ultraviolet (UV) absorbers in cosmetic products were separated and determined by high performance liquid chromatography. The recommended conditions for the analysis were as follows: column, 4.6 mm i.d. x 250 mm, Capcell Pak C18 SG (5 microns); detector, UV spectrophotometer (280 nm); column temperature, 40 degrees C; mobile phase, H2O-CH3OH (15:85 v/v) containing 3 mM stearyltrimethyl ammonium chloride; flow rate, 1.0 ml/min. In the case of the products containing 2-ethylhexyl p-methoxycinnamate (OMC) and/or 4-tert-butyl-4' methoxydibenzoylmethane (BMD), it was necessary to use H2O-1,4-dioxane (34:66 v/v) containing 6 mM stearyltrimethyl ammonium chloride as the mobile phase in order to separate OMC and BMD. Anthracene and 9,10-dimethylanthracene were used as an internal standard for the H2O-CH3OH mobile phase and the H2O-1,4-dioxane mobile phase, respectively. Calibration curves were linear within a range of 50 150 micrograms/ml for the 11 UV absorbers. Recoveries and reproducibilities of the method were satisfactory. By using this method, typical UV absorbers in several commercial cosmetic products such as lip creams, sun oils, lotions and emulsions were able to be rapidly determined without any interference. PMID- 1762057 TI - SC-46275: a potent, long-acting gastric antisecretory prostaglandin with low oral bioavailability in the dog. AB - The synthetic prostaglandin, SC-46275, an omega chain cyclopentenyl analog of enisoprost, was studied to determine its gastric antisecretory potency and duration of action in meal-stimulated innervated (Pavlov) pouch dogs and its p.o. bioavailability in unoperated fasted dogs. SC-46275 exhibited potent antisecretory activity when administered directly into the gastric pouch, the ED50 being 0.01 micrograms/kg. It had a long duration of antisecretory action; significant (P less than or equal to .05) inhibition of total acid output was observed 16 hr after intrapouch administration of 0.03 micrograms/kg. At this dose p.o., neither SC-46275 nor its free acid metabolite was detected in plasma. These data indicate that SC-46275 has novel properties: it is a potent, long acting gastric antisecretory agent which is not readily available systemically after p.o. administration. Thus, potential systemic side effects are expected to be absent or minimized at doses of SC-46275 which inhibit gastric acid secretion, and therefore it might be useful in peptic ulcer disease. PMID- 1762058 TI - Is staurosporine a specific inhibitor of protein kinase C in intact porcine coronary arteries? AB - We assessed the specificity of staurosporine, a putative protein kinase C inhibitor, for the enzyme in intact porcine coronary arteries by examining its effects on changes in intracellular free calcium level ([Ca++]i) and force induced by a phorbol ester, high KCl and caffeine. [Ca++]i was measured simultaneously with force by the fura-2 microfluorimetric method. Phorbol 12,13 dibutyrate (PDBu, 10(-6) M) produced a slowly developing and sustained contraction; however, [Ca++]i only increased slightly and transiently in the initial phase and then decreased gradually. On the other hand, 90 mM KCl elicited a contraction with a sustained increase in [Ca++]i. Staurosporine (10(-10) to 10( 7) M) applied 20 min before the addition of PDBu inhibited the PDBu-induced changes in [Ca++]i and force in a concentration-dependent manner. In contrast, staurosporine only at 10(-7) M reduced an increase in [Ca++]i and contractile force produced by 90 mM KCl. The inhibitory effects of staurosporine on PDBu- and KCl-induced contractions depended on exposure time. The [Ca++]i-force relationship obtained with variable concentrations of KCl was shifted slightly to the right by staurosporine at 10(-7) M. Furthermore, staurosporine even at 10(-7) M did not affect an increase in [Ca++]i by caffeine (25 mM), although it slightly attenuated a caffeine-induced contraction. These results suggest that staurosporine is a relatively specific inhibitor of protein kinase C in intact arteries at lower concentrations. At higher concentrations it may have actions unrelated to its inhibitory effect of protein kinase C, which include the inhibition of calcium influx into smooth muscle cells through the voltage dependent Ca++ channel. PMID- 1762059 TI - Central and peripheral injections of the 5-HT2 agonist, 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane, modify cardiovascular function through different mechanisms. AB - The mechanisms underlying the cardiovascular effects of central and peripheral administration of the 5-HT2 (serotonin) receptor agonist (+-)-1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane hydrochloride (DOI) were studied in conscious rats. Intravenous (10-1000 nmol/kg) and i.c.v. (3-300 nmol) administration of DOI produced dose-related elevations of arterial pressure without altering heart rate except after injection of the highest doses. Pretreatment with xylamidine tosylate, a 5-HT2 receptor antagonist that does not cross the blood-brain barrier, blocked the pressor response to i.v., but not i.c.v., administration of equivalent doses of DOI. Pretreatment with the vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced the pressor response to i.c.v., but not i.v., administration of DOI. Prior ganglionic blockade with chlorisondamine amplified the pressor response to both i.v. and i.c.v. administration of DOI. Pretreatment with a combination of chlorisondamine, xylamidine and d(CH2)5Tyr(Me)AVP abolished the pressor response to i.c.v. administration of DOI. Thus, the pressor response to i.v. administration of DOI was mediated at sites outside the blood-brain barrier, most likely at vascular 5-HT2 receptors, and was not secondary to vasopressin release. Inappropriate heart rate changes attended the pressor responses to i.v. administration of DOI, suggesting an action at extravascular sites. The pressor response to i.c.v. administration of DOI resulted from a combination of vasopressin release, modulation of autonomic nervous outflow and some leakage into the periphery. PMID- 1762060 TI - Presystemic acetylation of platelets by aspirin: reduction in rate of drug delivery to improve biochemical selectivity for thromboxane A2. AB - The utility of aspirin in the treatment of vascular occlusive disease has been ascribed to its blockade of platelet thromboxane A2 (TxA2), a potent inhibitor of vascular smooth muscle contraction and platelet aggregation. Coincident with the inhibition of TxA2 by aspirin at currently used dose regimens is a decrease in formation of prostacyclin (PGI2), an eicosanoid with opposing effects to TxA2 in vivo. The coincident inhibition of PGI2 could potentially limit the therapeutic efficacy of aspirin. This study addressed the issue as to whether a reduction in the rate of drug delivery could enhance the biochemical selectivity of aspirin toward inhibition of TxA2. Intubation studies were performed in parallel groups of healthy volunteers in which a 50-mg aspirin dose was administered as either a bolus or a 5 or 10 mg/hr infusion via a nasogastric tube. A control group received buffer solution. Systemic plasma levels of aspirin, major urinary metabolites of TxA2 and PGI2 and serum thromboxane B2 levels ex vivo were evaluated. Relative to the group receiving bolus aspirin, the slower rates of aspirin delivery increased the effective selectivity of the administered aspirin for TxA2. To investigate further this apparent selectivity, controlled release (CR) dose forms of aspirin were prepared and evaluated in a preliminary dose ranging study in healthy subjects. The doses studied were 50 and 75 mg CR and a 75-mg aspirin solution. The CR aspirin dose forms decreased the maximal plasma concentration of aspirin relative to a bolus dose. The pharmacodynamic effects of the CR formulations were assessed via measurement of ex vivo serum thromboxane B2 formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762061 TI - Stimulation of sodium transport by duramycin in cultured human colonic epithelia. AB - Effects of two peptide antibiotics, duramycin and Ro 09-0198, on ion transport in cultured human colonic epithelia were investigated. Both peptides acted on the apical face of epithelial monolayers, causing an increase in ion transport measured as short circuit current. Concentration-response relationships were complex, because above a concentration of 2 to 5 microM, the peptides caused currents either to decline toward zero or become large and unstable. Ion substitution experiments showed that the majority of the current response was due to electrogenic sodium absorption. An outward chloride current could also be induced by duramycin, provided an outwardly directed chloride gradient was imposed. It was also shown that the peptides could increase [Ca]i, probably by creating entry sites in the apical face. Duramycin was also able to create large conductance (2000 pS) channels in "black" lipid bilayers. It is proposed that the antibiotics interact with membrane lipids in the apical faces of colonic epithelia to create artificial nonspecific ion channels. The prevailing electrochemical gradients which exist when the epithelia are bathed symmetrically in Krebs-Henseleit solution result in increased electrogenic sodium transport. No evidence was found for colonic epithelia that duramycin or Ro 09-0198 interacted specifically with either membrane channels or receptors to increase ion transport. PMID- 1762062 TI - Activities of lung NADPH-cytochrome C-reductase and of cytochrome P-450 peroxidase during the protection of rat from hyperoxic injury by polyriboinosinic acid-polyribocytidilic acid. AB - Rats exposed to normobaric oxygen received a single i.p. injection of 2.5 mg/kg of poly I: poly C at various times (-120 to +36 h) before and after the beginning of oxygen exposure. Hyperoxic lung damage and modifications in cytochrome P-450 system components were evaluated. Our results confirmed the protective effect of poly I: poly C on rats exposed to oxygen, reducing the lung edema and the mortality. This effect was only observed when poly I: poly C was injected 48 or 36 h before the beginning of oxygen exposure. Although oxygen exposure per se decreased the total level of lung cytochrome P-450, poly I: poly C per se induced a deeper decrease to levels similar in air- or oxygen-exposed rats. Poly I: poly C did not modify the NADPH-cytochrome c reductase level nor the cytochrome P-450 peroxidase activity in air-exposed rats. The oxygen exposure induced a decrease of these two enzymes, either in the absence or in the presence of poly I: poly C, except when poly I: poly C was injected 48 or 36 h before the beginning of oxygen exposure, times at which poly I: poly C restored the enzymatic values measured in rats exposed to air. Because the times of injection of poly I: poly C were those at which the protective effect was observed, it suggested that the protective effect of poly I: poly C against oxygen toxicity was associated with a lack of oxygen-induced decrease of both the lung NADPH-cytochrome c reductase level and the lung cytochrome P-450 peroxidase activity. PMID- 1762063 TI - Imipramine as a discriminative stimulus. AB - The tricyclic antidepressant imipramine was established as a discriminative stimulus in pigeons at two doses (3.0 or 5.6 mg/kg). Because imipramine has multiple effects on different neurotransmitter systems, a range of compounds from several pharmacological classes were tested for substitution. The tricyclic antidepressants desipramine, amitriptyline and doxepin, all of which block serotonin (5-HT) and norepinephrine (NE) reuptake, resulted in imipramine-key responding. The psychomotor stimulants cocaine and d-amphetamine also occasioned responding on the imipramine key, as did the NE reuptake inhibitor tomoxetine; nomifensine, which blocks the reuptake of both NE and dopamine (DA), also resulted in responding on the key correlated with imipramine injections. Bupropion, a DA reuptake inhibitor, resulted in drug key responding but substitution did not occur with another DA uptake inhibitor GBR 12909. The alpha 2 agonist clonidine, the 5-HT2 antagonist ritanserin or the 5-HT reuptake inhibitor fluoxetine also did not occasion drug-key responding. Drug-appropriate responding occurred in pigeons trained at the lower dose of imipramine with the 5 HT1A compounds 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide and gepirone; partial substitution occurred in pigeons trained with the higher dose of imipramine. Substitution for the imipramine stimulus by gepirone, an antidepressant with actions mediated by the 5-HT1A receptor, as well as with 8 hydroxy-2-(di-n-propylamino)tetralin hydrobromide, suggests that imipramine may have effects at this receptor site and confirms reports that compounds active at this receptor may have antidepressant activity. This appears to be the first report of the successful, long-term establishment of imipramine as a discriminative stimulus without the development of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762064 TI - Effects of GABA in the morphine-tolerant longitudinal muscle, myenteric plexus preparation of the guinea pig. AB - The effect of chronic treatment with morphine via pellet implantation on the sensitivity of the longitudinal smooth muscle-myenteric plexus of the guinea pig ileum to the contractile effects of gamma-aminobutyric acid (GABAA)-receptor agonists was assessed. GABA and muscimol elicited concentration-dependent contractions of the longitudinal smooth muscle which were due to the release of acetylcholine because the contractile effects were markedly attenuated by atropine (10 nM). The contractile action of GABA agonists does not involve an intermediate step mediated by nicotinic receptors because the concentration response curves for GABA were unaffected by hexamethonium (1 mM). Bicuculline (10 microM) produced nearly equivalent rightward shifts of the concentration-response curves for both GABA and muscimol, indicating mediation of the contractile effects of these agents by GABAA receptors. Chronic exposure to morphine via pellet implantation did not alter the sensitivity of this preparation to either GABA or muscimol. This is in contrast to the development of supersensitivity of the longitudinal smooth muscle-myenteric plexus to other excitatory agonists (nicotine, 5-hydroxytryptamine and potassium), which accompanies the development of tolerance to opioids. GABA induces depolarization of myenteric neurons that is observed most prominently in AH neurons and rarely in S neurons. The stimulatory effects of nicotine and of GABA were inhibited by morphine (a predominantly mu opioid agonist) and by U50,488H (a predominantly kappa opioid agonist). The results are discussed within the context that supersensitivity to neuronal stimulants of the myenteric plexus in morphine-tolerant preparations is limited to substances which depolarize S neurons. PMID- 1762065 TI - Distribution and analgesia of [3H][D-Pen2, D-Pen5]enkephalin and two halogenated analogs after intravenous administration. AB - To improve pharmacological characteristics of the delta-selective, cyclic peptide [D-Pen2, D-Pen5]enkephalin (DPDPE), modification by halogenation at the Phe4 residue was undertaken. The present study was to determine the extent [3H]DPDPE, [3H][p-Cl-Phe4]DPDPE and [p-125IPhe4]DPDPE crosses the blood-brain barrier, elicits analgesia and to characterize selective organ distribution and stability after i.v. administration. A significantly greater percentage of total [3H][p-Cl Phe4]DPDPE reached the brain after 10, 20 and 40 min as compared to [3H]DPDPE and both peptides were significantly displaced by pretreatment with naloxone or naltrindole. The amount of [3H]DPDPE detected in the brain was greater than that of [p-125IPhe4]DPDPE. Distribution results revealed large amounts of the administered peptides were sequestered rapidly in the gall bladder and secreted into the small intestine. Hot-plate antinociception tests 5 min after i.v. administration (30 and 60 mg/kg) revealed [p-Cl-Phe4]DPDPE to elicit a much greater analgesic effect as compared to DPDPE or [p-125IPhe4]DPDPE. These results provide evidence that [p-Cl-Phe4]DPDPE has a greater apparent distribution to the brain and has a greater effect on the antinociception threshold as tested on the hot-plate than DPDPE or [p-125IPhe4]DPDPE. Stability of unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE was determined both in vitro and in vivo; both unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE remain intact. PMID- 1762066 TI - [3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes as a measure of nicotine-induced changes in membrane potential. AB - The effect of nicotine on synaptosomal membrane potential in P2 preparations of rat cerebral cortex was investigated using a membrane permeant, lipophilic cation, [3H]tetraphenylphosphonium ([3H]TPP+). [3H]TPP+ accumulated in synaptosomes in a time-dependent manner and its accumulation was decreased when the extracellular potassium concentration was increased and in the presence of the sodium channel toxin, veratridine. Nicotine (1-1000 microM) decreased the accumulation of [3H]TPP+ in both P2 synaptosomal preparations and in synaptosomes purified using Percoll gradients. This effect of nicotine was mimicked by other nicotinic agonists (1,1-dimethyl-4-phenylpiperazinium iodide, cytisine, suberyldicholine and acetylcholine) and was partially blocked by 10 microM mecamylamine and 30 microM hexamethonium. Atropine (1 microM) and the removal of calcium from the incubation mixture both enhanced the effect of nicotine while the addition of physostigmine (10 microM) reduced the nicotine-induced decrease in [3H]TPP+ accumulation, evidence that acetylcholine released from the synaptosomes by nicotine may produce hyperpolarization of synaptosomes via stimulation of presynaptic muscarinic receptors. It is concluded that the effect of nicotine on [3H]TPP+ accumulation is mediated by nicotine stimulation of a ganglionic-type nicotinic cholinergic receptor and that this method of determining synaptosomal membrane potential will provide a functional measure of presynaptic nicotinic receptor activation. PMID- 1762067 TI - Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. AB - Using stable isotope methodology, we studied the effect of the enantiomeric composition of dosage form on ibuprofen metabolism. Eight healthy human subjects received racemic ibuprofen (800 mg) plus S-[aromatic-2H4]ibuprofen (10 mg), R ibuprofen (600 mg) plus S-[aromatic-2H4]ibuprofen (10 mg) and S-ibuprofen (600 mg) orally on separate occasions in random order. Stereoselective gas chromatography-mass spectrometry was used to quantify deuterated and nondeuterated ibuprofen in serum up to 24 h postdose. Urinary excretion of the stereoisomeric forms of carboxyibuprofen, hydroxyibuprofen and ibuprofen glucuronide were determined up to 24 h postdose by stereoselective high performance liquid chromatography. The metabolism of ibuprofen enantiomers was not influenced by the enantiomeric composition of the dose. For racemic ibuprofen, the mean clearances (+/- S.D.) of S-ibuprofen, R-ibuprofen inversion and R-ibuprofen noninversion were 87.4 +/- 25.9, 57.3 +/- 31.0 and 56.3 +/- 29.0 ml/min, respectively. The fractional inversion of ibuprofen was significantly greater (P less than .05) using the stereochemical composition of the urinary metabolites (0.63 +/- 0.05) vs. the method using the clearance of deuterated S ibuprofen (0.51 +/- 0.08) after the dose of racemate. Unreliable estimates of fractional inversion were obtained when the S-ibuprofen and racemic ibuprofen doses were combined. Metabolite formation clearances suggested that S-ibuprofen is preferred over R-ibuprofen in the formation of hydroxyibuprofen, carboxyibuprofen and ibuprofen glucuronide. Product stereoselectivity in the formation of the four diastereomers of carboxyibuprofen was modest in favor of SS and RR-carboxyibuprofen for S- and R-ibuprofen, respectively. PMID- 1762068 TI - The reinforcing and subjective effects of morphine in post-addicts: a dose response study. AB - The reinforcing and subjective effects of morphine were determined in five human volunteers with histories of i.v. heroin abuse. Subjects responded under a second order schedule of i.m. injection. Under this schedule, every 100 lever presses produced a brief stimulus light [fixed ratio (FR) 100:s]; the 30th completion of the FR 100 requirement turned on the light for 15 min and the subject received an i.m. injection of morphine [FR 30 (FR 100:s)]. Once each weekday morphine or placebo was available under this schedule. Each drug dose was available for 1 week. Under these conditions placebo did not maintain responding; 3.75 mg of morphine maintained responding in four of five subjects, and higher morphine doses (7.5, 15 and 30 mg) maintained responding in all five subjects. Subjective effects were measured concurrently: these included measures of drug liking, the Morphine Benzedrine Group scale of the Addiction Research Center Inventory, drug detection and identification. Subjects did not report subjective effects different from placebo for the lowest dose of morphine; the intermediate doses of morphine produced inconsistent effects, and the highest dose of morphine occasioned reports of drug liking and "dope" identifications. These results indicate that there can be a significant dissociation of the reinforcing and the subjective effects of opioids, which has implications for theories of opioid abuse, particularly those assuming that the reinforcing effects are causally related to the euphoric effects of opioids. Furthermore, these results confirm that measures of reinforcing effects and measures of subjective effects do not necessarily lead to identical predictions when used to assess the liability for abuse of a substance. PMID- 1762069 TI - Evaluation of the central and peripheral components for induction of postural hypotension by guanethidine, clonidine, dopamine2 receptor agonists and 5 hydroxytryptamine1A receptor agonists. AB - Previously, it was observed that the severity of postural hypotension in rats after i.v. administration is: guanethidine (severe) greater than clonidine greater than dopamine2 (DA2) receptor agonists greater than 5-hydroxytryptamine1A (5-HT1A) receptor agonists (none). In this paper we investigated central and peripheral mechanisms involved in postural hypotension induced by these drugs. Intracerebroventricular or intracisternal doses of the above agents produced a fall in mean arterial pressure of 32 to 42 mm Hg and were used for evaluation of the central component. Intracerebroventricular, but not intracisternal, clonidine induced postural hypotension. DA2 or 5-HT1A receptor agonists did not induce postural hypotension after either i.c.v. or intracisternal administration. Intracerebroventricular guanethidine did not lower arterial pressure dose dependently, or did it produce postural hypotension. A peripheral action postulated to be involved in the postural hypotension was inhibition of sympathetic neurotransmission; to evaluate this inhibition, drug effects on pressor and tachycardiac responses elicited by electrical stimulation in pithed rats were determined. Inhibition of heart rate changes by each of the drugs was: guanethidine, 60 to 100% at 0.1 to 8.0 Hz; clonidine, 20 to 40% at 0.1 to 2.0 Hz; DA2 receptor agonists, 10 to 45% at 0.1 to 2.0 Hz; and 5-HT1A receptor agonists, 20 to 40% at less than or equal to 0.5 Hz. These data indicate that the frequency selective inhibition in the peripheral sympathetic nervous system may explain the likelihood of postural hypotension for guanethidine, clonidine DA2 and 5-HT1A receptor agonists. Clonidine has some central component for induction of postural hypotension in addition to the frequency-related peripheral component. PMID- 1762070 TI - Characterization of the renal effects and renal elimination of sulotroban in the dog. AB - The renal effects and renal handling of the nonprostanoid thromboxane receptor antagonist, sulotroban (4-[2-(phenylsulfonylamino)ethyl]phenoxyacetic acid), were characterized in dogs. Sulotroban was infused i.v. at 0.06, 0.2, 0.6 and 1.0 mg kg-1 min-1 (plus prime) for 180 min. Arterial blood pressure was reduced significantly during infusion of the 1.0 mg kg-1 min-1 dosage only. Diuresis, characterized by increases in both fractional and absolute urinary excretion of sodium, potassium, chloride and calcium, and decreases in urine osmolality occurred at each of the sulotroban dosages tested. The renal clearance of sulotroban exceeded the glomerular filtration rate, suggesting renal secretion of sulotroban. The transport maximum for sulotroban secretion was approximately 160 micrograms kg-1 min-1. Renal cortical slices from naive dogs accumulated [14C]sulotroban against a concentration gradient. Sulotroban accumulation was blocked by metabolic inhibitors (dinitrophenol and sodium azide) and inhibitors of organic anion transport (probenecid and p-aminohippurate), but not by inhibitors of organic cation transport (cyanine and tetraethylammonium), suggesting that tubular secretion of sulotroban is mediated by an organic anion transport system. It was concluded that: 1) decreases in blood pressure occurred only after high dosages and were associated with high plasma sulotroban concentrations; 2) diuresis occurred at all dosages and may represent a separate pharmacological action unrelated to thromboxane receptor antagonism; and 3) renal excretion of sulotroban in the dog occurs by both filtration and tubular secretion with secretion occurring via an organic acid transporter. PMID- 1762071 TI - Expression of monomorphic arylamine N-acetyltransferase (NAT1) in human leukocytes. AB - The expression of arylamine N-acetyltransferase (NAT) in leukocytes was investigated using p-aminobenzoic acid (PABA) and sulfamethazine (SMZ), substrates which are preferentially acetylated by the monomorphic NAT1 and polymorphic NAT2 enzymes, respectively. Activity towards both substrates was detected in mononuclear leukocytes (MNL; preparation containing approximately 80% lymphocytes), monocytes and neutrophils. PABA and SMZ acetylation rates were highly correlated in each of the isolated cell types. The NAT in leukocytes displayed a much higher affinity and turnover rate for the acetylation of PABA than for SMZ. These kinetic characteristics suggest that the acetylating activity in human leukocytes is predominantly attributable to the monomorphic enzyme NAT1. Neutrophils showed evidence of biphasic kinetics for SMZ which would indicate the coexpression of NAT1 and low levels of the polymorphic enzyme, NAT2. NAT activity in MNL was not influenced by the acetylator phenotype of the individual. There was, however, a significant correlation between NAT activity in MNL and the in vivo acetylation (urinary metabolite ratio) of p-aminosalicylic acid, which is monomorphically acetylated in humans. The expression of NAT1 in leukocytes and the virtuall absence of NAT2 may have important toxicological implications. The in vitro/in vivo correlation suggests that leukocytes may be a useful marker of systemic NAT1 activity. PMID- 1762072 TI - Pharmacokinetics and metabolism of nilutamide in the isolated rat lung. AB - Nilutamide (N) is a potent antiandrogen used in the treatment of diffuse carcinoma of the prostate. The drug has been implicated in a few instances of pneumonitis in man. The present studies were carried out to examine N disposition in the isolated perfused lung (IPL) from rats. Both recirculating and single-pass IPL were used. Recirculation was run for 60 min at concentrations of N ranging between 12 and 120 microM (+1 mu Ci [14C]N). Single-pass perfusions were run for 30 min (uptake, 10 min; efflux, 20 min) at inflowing concentrations ranging from 12 to 480 microM (+1 mu Ci [14C]N). Nilutamide was concentrated in the recirculating IPL, and tissue to medium ratio (T/M) ranged between 6.6 and 4.2, depending on the inflowing concentration of N (Cin). High performance liquid chromatography analysis of extracts of 60-min lung homogenates demonstrated the primary amino metabolite of N in addition to the parent compound. This indicated reduction of the nitro moiety of N by lung tissues. At 60 min and Cin = 40 microM, 17.6 +/- 4.7% of the radioactivity present in lung was accounted for by the metabolite. Perfusate samples contained low to undetectable amounts of the metabolite. No metabolism of N was detected in single-pass IPL, possibly because of the shorter duration of experiments. Amount of N taken up in lung and T/M were similar to those found in recirculating preparations. Uptake of N in the single pass IPL was proportional to N concentration up to 480 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762073 TI - Effects of endothelin-3 on renal functions. AB - The effects of L-NGnitroarginine (LNNA), a nitric oxide synthase inhibitor, and ibuprofen, a cyclooxygenase inhibitor, on the renal actions induced by endothelin (ET)-3 were studied in anesthetized dogs. Continuous infusion of ET-3 in a dose of 5 ng/kg/min for 25 min increased both renal blood flow (RBF) and urine flow rate. In dogs given LNNA (75 micrograms/kg/min for 25 min), the RBF decreased after intrarenal administration of ET-3 (5 ng/kg/min). Glomerular filtration rate (GFR) was unchanged throughout the infusion of ET-3, in dogs treated with and without LNNA. In dogs given ibuprofen (12.5 mg/kg i.v.), an initial increase in RBF was evident after initiating infusion of the peptide, to be followed by a gradual reduction in RBF, GFR decreased significantly with ET-3, whereas the degree of reduction in RBF was the same in dogs treated with LNNA. Thus, ET-3 acts as a vasodilatory and diuretic peptide in the dog kidney. Presumably ET-3 enhances the release of nitric oxide and prostaglandins and then renal vasodilation occurs. Although the enhanced production of prostaglandins by ET-3 may be responsible for maintaining GFR, it is not linked to the initial phase of renal vasodilation. PMID- 1762074 TI - A nonprimate animal model applicable to zidovudine pharmacokinetics in humans: inhibition of glucuronidation and renal excretion of zidovudine by probenecid in rats. AB - The monkey is considered the best animal model to study the pharmacokinetics of zidovudine (azidothymidine, AZT) because humans and monkeys eliminate 60 to 75% of AZT by metabolism to the 5'-O-glucuronide (GAZT), in contrast to other experimental animals, which excrete most of the drug unchanged in the urine. It has become increasingly difficult and costly to use monkeys in research. Therefore, we undertook studies to determine the suitability of the rat as an alternative animal model to study the pharmacokinetics of AZT. In the initial experiments, [3H]AZT was administered i.v. at doses of 19, 60 and 187 mumol/kg to male Sprague-Dawley rats with intact bile ducts. The respective values (mean +/- S.D.) for total clearance of AZT were 2.4 +/- 0.2, 2.3 +/- 0.3 and 1.8 +/- 0.4 l/hr/kg and for renal clearance were 1.7 +/- 0.2, 1.8 +/- 0.4 and 1.5 +/- 0.4 l/hr/kg. The renal clearance of AZT was approximately equal to renal plasma flow of rats (1.5 l/hr/kg), suggesting that in addition to filtration, AZT is also efficiently secreted in the kidney of the rat. The respective values for volume of distribution at steady state were 1.3 +/- 0.2, 1.0 +/- 0.2 and 0.84 +/- 0.19 l/kg (P less than .05) and elimination half-life were (harmonic mean) 0.55, 0.44 and 0.46 hr. Urinary excretion of AZT as unchanged drug in intact rats accounted for 70 +/- 6, 79 +/- 6, and 83 +/- 12% of the dose, whereas only 0.7 to 0.8% of the dose was recovered in the urine as GAZT. Rats with exteriorized bile ducts, the proposed alternative animal model, were given an i.v. dose of 60 mumol/kg of [3H]AZT. To test the effect of a concurrently administered drug on the elimination of AZT in the model, some rats with bile duct cannulas were pretreated with probenecid, a known inhibitor of AZT elimination in humans. Urine and bile were collected to quantify the formation of GAZT. GAZT was identified by fast atom bombardment mass spectrometry as the major metabolite of AZT in the rat. GAZT excretion in the bile and urine accounted for 11 +/- 3% of the dose in saline-treated rats, compared to only 1.4 +/- 0.3% in rats treated with probenecid (P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762075 TI - Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung. AB - An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body. PMID- 1762076 TI - Ethanol potentiates gamma-aminobutyric acid-mediated inhibition in the inferior colliculus: evidence for local ethanol/gamma-aminobutyric acid interactions. AB - The effect of ethanol on gamma-aminobutyric acid (GABA)-mediated inhibition of neurons of the inferior collicular cortex (IC) was investigated. Systemic administration of 0.5 g/kg ethanol, but not 0.25 g/kg ethanol, potentiated the inhibitory effect of GABA on IC neuronal activity. As with systemic administration of ethanol, local application of two concentrations of ethanol potentiated, in a dose-dependent and concentration-dependent manner, GABA mediated inhibition of IC activity. When utilizing the lower ethanol concentration (270 mM), increasing ethanol ejection currents produced a correspondingly greater amount of augmentation of GABA inhibition without concomitant changes in spontaneous neural activity. At the highest ejection current tested (90 nA), ethanol doubled the inhibitory effects of GABA on IC neuronal activity. Local application of a higher concentration of ethanol (2.7 M) also potentiated GABA-mediated inhibition, with greater ejection currents producing greater potentiation of GABA-inhibition. Compared to the lower ethanol concentration, the higher ethanol concentration required lower ejection currents to produce comparable amounts of potentiation of GABA inhibition. These findings demonstrate that ethanol potentiates GABA inhibition of IC activity via a local action. In contrast to the effects of ethanol on GABA inhibition, locally applied ethanol failed to potentiate the inhibition by glycine of IC activity, indicating that ethanol does not indiscriminately potentiate all types of inhibition of IC neural activity. Additionally, locally applied ethanol failed to potentiate inhibition by GABA in the lateral septum, indicating that ethanol/GABA interactions are site specific. These findings indicate that ethanol specifically potentiates GABA-mediated inhibition of neural activity, and that this action occurs via a local action at specific sites in brain. PMID- 1762077 TI - Species variation in pulmonary endothelial aminopeptidase P activity. AB - Pulmonary endothelial aminopeptidase P (AmP) may be an important contributor to the inactivation of circulating bradykinin in certain species. To examine this possibility, we measured AMP activity in vivo and in vitro using Arg-Pro-Pro [3H]benzylamide (3H-APPB) as substrate under conditions of first order enzyme kinetics. Utilizing multiple indicator dilution techniques, metabolism of 3H-APPB to Arg and Pro-Pro-[3H]benzylamide by AmP was not detectable during a single transpulmonary passage in anesthetized rabbits (n = 4), cats (n = 3) and pigs (n = 4). However, percent metabolism of 3H-APPB ranged from 54 to 63% in anesthetized rats (n = 6). In all experiments, the substrate remained within the vascular space and was thus accessible to endothelial and blood AmP only. At the same time, single-pass transpulmonary percent metabolism of [14C]benzoyl-Ala-Gly Pro by endothelial-bound angiotensin converting enzyme was remarkably similar among rabbits, cats, rats and pigs (60-65%). In culture, Vmax/Km of AmP was 3 to 10 x 10(-4) min-1 for human basal arterial and rabbit and bovine pulmonary arterial endothelial cell monolayers (2 x 10(5) cells). AmP activity in the supernatant of lung and kidney tissue (homogenized in saline containing 1-o-n octyl-beta-glucopyranoside) from rabbit, cat, pig and rat expressed as Vmax/Km(min-1) per (g wet tissue/ml) was 0.74, 2.25, 3.91 and 185.8 (lung), and 1.0, 3.7, 8.4 and 438.3 (kidney), respectively. Similarly, Vmax/Km values of AmP in plasmas of cat, dog, rabbit, pig, calf (serum), human and rat were 0, 0.016, 0.025, 0.068, 0.191, 0.237 and 3.53 min-1. These results suggest that 1) there are large interspecies variations in AmP activities of plasma, lung and kidney; 2) of the species studied, the rat contains the largest activities of AmP; and 3) AmP appears to be located on the luminal surface of the rat pulmonary endothelium. PMID- 1762078 TI - Evidence against serotonin-induced endothelium-dependent relaxation in bovine coronary artery. AB - Bovine coronary artery rings were mounted in tissue baths for the measurement of isometric contraction in order to test for serotonin-induced endothelium dependent relaxation. A23187 caused a concentration-dependent relaxation in precontracted artery rings when the endothelium was intact, but not when it was removed. Endothelium removal had no effect on serotonin concentration contractile response curves (CRC) in normal Krebs' solution, but enhanced the response to serotonin in artery rings precontracted with 25 mM K+ Krebs' solution. In endothelium-intact, precontracted artery rings, ketanserin shifted the serotonin CRC to the right, but did not convert the contraction to relaxation. 5 Carboxamidotryptamine caused a weak contraction that was blocked by ketanserin, but not converted to relaxation. Inactivation of monoamine oxidase enhanced the contractile response to serotonin in precontracted artery rings in a manner identical to that caused by endothelium removal. Inactivation of monoamine oxidase had no effect in endothelium-denuded artery rings. De-endothelialized rabbit aorta strips pretreated with phenoxybenzamine were placed in close apposition to endothelium-intact coronary artery strips. Superoxide dismutase, acetylcholine and A23187 caused the precontracted rabbit aorta strip to relax, whereas serotonin had no effect. These results support the conclusion that the endothelium of the bovine coronary artery releases a relaxing factor both spontaneously and in response to acetylcholine and A23187. Serotonin appears to be incapable of releasing endothelium-derived relaxing factor or causing an endothelium-dependent relaxation. However, bovine coronary artery endothelium appears to be able to take up and metabolize serotonin. PMID- 1762079 TI - Effect of intranasal capsaicin on symptoms and mediator release. AB - Differential nasal responsiveness to environmental tobacco smoke (ETS) has been documented in humans and we hypothesized that this reflects differential responsiveness to c-fiber stimulation. We compared the response to intranasal capsaicin in subjects with and without a history of ETS-rhinitis. We challenged 10 ETS-sensitive and 11 ETS-nonsensitive subjects intranasally with 25 mg of lactose powder followed by 25 pg to 25 ng of capsaicin in 25 mg of lactose. Subjects rated nasal symptoms and underwent nasal lavage. In each lavage, the concentrations of albumin (an index of vascular permeability), kinins and histamine (a marker of mast cell activation) were measured. Nasal lavage tosyl-L arginine methyl ester (TAME)-esterase activity, which can be a reflection of mast cell activation, increased vascular permeability or glandular secretion, was also determined. Subjects with a history of ETS-rhinitis reported more rhinorrhea than subjects without a history of ETS-rhinitis (P less than .01). No significant increase occurred in nasal lavage histamine, albumin or kinins in either subject group. TAME-esterase activity (presumably a reflection of increased glandular secretion) increased greater than 1000 cpm in 12/21 subjects (designated "TAME producers"), but this was unrelated to ETS-sensitivity. TAME producers showed a dose-dependent increase in TAME-esterase activity, whereas TAME nonproducers showed no change at any capsaicin dose. We conclude that capsaicin causes nasal symptoms and glandular stimulation without evidence of increased vascular permeability or mast cell activation. ETS-rhinorrhea symptoms in humans appear related to c-fiber stimulation. The absence of c-fiber-induced glandular secretion, although not related to ETS-sensitivity, was associated with decreased sneezing and increased symptoms of capsaicin-induced nasal burning. PMID- 1762080 TI - Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11. AB - Anti-liver kidney microsomes (anti-LKM2) autoantibodies, appearing in patients treated with tienilic acid and suffering from hepatitis, react with proteins in rat liver sections. The nature of the rat proteins responsible for this recognition and detection of anti-LKM2 has been investigated. Immunoblot testing of the anti-LKM2 with liver microsomes from diversely treated rats and with purified rat liver cytochromes P450 (IA1, IA2, IIB1, IIB2, IIC6, IIC11 and IVA1) showed that these antibodies cross-reacted with cytochrome P450IIC11 and also with phenobarbital-induced cytochromes P450IIB1 and IIB2. Moreover, metabolic activation of tienilic acid and of a tienilic acid isomer by untreated rat liver microsomes was partially inhibited by anti-LKM2. On the other hand, monospecific polyclonal anti-rat P450IIC11 antibodies cross-reacted with human microsomal cytochromes P450 and recognized the same cytochromes P450 as anti-LKM2. This antibody also gave an immunofluorescence pattern on rat and mouse liver and kidney sections very similar to anti-LKM2. The data presented here show that anti LKM2 recognize epitopes shared by rat P450 IIC11, and a human P450 of the family IIC. All the results indicate rat P450 IIC11, the major isoenzyme present in normal adult male rat liver, as the main antigen recognized by human anti-LKM2 autoantibodies; this is the basis of the immunofluorescence test for detection of these antibodies. PMID- 1762081 TI - 5-Hydroxytryptamine1C/2 agonists in the thoracic spinal cord: cardiovascular effects and binding sites in the intermediolateral cell column. AB - The presence of 5-hydroxytryptamine (5-HT)1C/2 binding sites in autonomic regions of the thoracic spinal cord and their role in the regulation of sympathetic outflow to the cardiovascular system were examined. Light microscopic receptor autoradiography was used to visualize the binding of the 5-HT1C/2 ligand, [125I] 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [( 125I]DOI). In thoracic spinal cord, a discrete and preferential localization of specific [125I]DOI binding sites was found in the intermediolateral cell column. To determine the mean arterial pressure (MAP) and heart rate (HR) effects resulting from activation of 5-HT1C/2 receptors in spinal cord, DOI and alpha-methyl-5-HT were administered intrathecally (i.t.) to anesthetized, artificially ventilated rats. DOI (1-100 micrograms) caused initial decreases followed by increases in MAP and HR, whereas alpha-methyl-5-HT (1-30 micrograms) only decreased MAP and HR. The distribution of [125I]DOI after i.t. administration and the effects of a peripherally administered 5-HT1C/2 antagonist 6-methyl-1-(1-methylethyl)-ergoline-8 beta carboxylic acid, 2-hydroxyl-1-methyl propyl ester and maleate salt (LY53857) showed that the pressor effects of i.t. DOI were due to peripheral leakage and suggested that the depressor effects were due to a spinal site of action. The depressor effects of DOI were prevented by peripheral administration of phentolamine. Pretreatment with i.t. administration of 5-HT1C/2 antagonists (LY53857, ketanserin and mianserin) did not block the depressor or bradycardic effects of i.t. administration of DOI. Only LY53857 was effective in blocking the depressor effects of i.t. administration of alpha-methyl-5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762082 TI - Functional studies in the human submandibular duct cell line, HSG-PA, suggest a second salivary gland receptor subtype for nucleotides. AB - Extracellular nucleotides, acting through P2 purinoceptors, have been implicated in the regulation of ion transporting epithelia, including salivary gland acini. Multiple P2 purinoceptor subtypes have been suggested, including P2X, P2Y and P2U (or nucleotide) subtypes, as well as the P2Z subtype found in rat parotid acinar cells. We investigated responses to ATP, ATP analogs and UTP in transformed human submandibular gland duct cells (HSG-PA), in order to compare duct cell purinoreceptors with those in acinar cells. ATP, UTP and some ATP analogs increased, with different potencies, inositol phosphate accumulation, calcium mobilization and potassium efflux. Nucleotide-stimulated calcium mobilization occurred in the absence of, but was enhanced by, extracellular calcium, and maximal potassium efflux required extracellular calcium. UTP and ATP demonstrated equal potencies of about 1 microM and similar efficacies in eliciting these responses, and identical rank orders of potency for stimulating calcium mobilization and potassium efflux were obtained: UTP = ATP greater than ATP gamma S greater than ADP greater than ADP beta S, with alpha,beta-methylene-ATP and 2 methylthio-ATP having little or no effect. Agents reported to block nucleotide effects in parotid acini were ineffective in HSG-PA cells, and experiments in Mg(++)- and Ca(++)-free medium did not indicate that a form of ATP other than MgATP was the active species at the HSG-PA purinoceptor. The extracellular nucleotide effects were not altered by pertussis toxin. These results indicate the presence of a P2U or nucleotide receptor subtype in HSG-PA submandibular duct cells distinguishable from the P2Z purinoceptor of rat parotid acinar cells, suggesting involvement of multiple nucleotide receptor subtypes in salivary gland regulation. PMID- 1762083 TI - Pharmacokinetics of 18F-labeled fluconazole in rabbits with candidal infections studied with positron emission tomography. AB - [4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in normal and infected animals. The biodistribution of fluconazole was determined after administration of the 18F-tracer with/without a pharmacological dose of unlabeled drug by radioactivity measurements on excised tissues. In normal rabbits and rabbits with candidal infection of the thigh, tissue concentrations of drug were determined by serial positron emission tomographic imaging. In rats, coinjection of tracer quantities of [4-18F]fluconazole with a pharmacological dose of unlabeled drug resulted in a relatively uniform distribution of radioactivity in most organs, whereas, when the 18F-tracer was injected alone, spleen, muscle and heart accumulation was decreased and liver accumulation was increased. In rabbits, this effect was less pronounced. Early accumulation of [4 18F]fluconazole was greater in infected muscle. The areas under the 2-hr uptake curves were 4.30 and 6.05 micrograms.hr.ml-1 for normal and infected tissue. A mathematical model was used to summarize the kinetics of fluconazole in normal and infected muscle. The model hypothesizes that fluconazole is compartmentalized in blood and tissue, with rate constants describing the transition between compartments. Direct measurement of the partition coefficient of fluconazole in muscle and predictions of the kinetic model were in close agreement, suggesting that fluconazole enters muscle via a passive transport mechanism. Transport rates of fluconazole, into (Kin) and out of tissue (kout), were increased in infected compared with normal muscle, possibly due to increased capillary permeability (Kin: 0.064 +/- 0.001 vs. 0.0270 +/- 0.0002, kout: 0.063 +/- 0.002 vs. 0.035 +/- 0.001). PMID- 1762084 TI - Pharmacological characterization of serotonin-O-carboxymethyl-glycyl tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites. AB - The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects. PMID- 1762085 TI - Rapid dissociation of platelet-rich fibrin clots in vitro by a combination of plasminogen activators and antiplatelet agents. AB - Thrombin promotes the formation of arterial thrombi by converting fibrinogen to fibrin and by causing platelets to aggregate. We have examined the combined effects of plasminogen activators and inhibitors of platelet aggregation on the lysis of platelet-rich fibrin clots formed by alpha-thrombin in citrated platelet rich plasma. The extent of platelet aggregation and clot formation were measured by recording light transmission in an aggregometer. Immediately after the formation of platelet-rich fibrin clots, addition of 2,000 U/ml streptokinase or 50 micrograms/ml recombinant tissue-type plasminogen activator alone resulted in the degradation of polymerized fibrin and the release of trapped platelet aggregates without causing significant platelet deaggregation. Preincubation of the platelet-rich plasma with 20 microM indomethacin for 1 min before thrombin stimulation or simultaneous addition of prostaglandin E1 (10 microM) with the plasminogen activators after thrombin stimulation resulted in spontaneous platelet deaggregation. Because platelet aggregation is, in part, mediated by the binding of Arg-Gly-Asp-containing adhesive proteins to activated platelets, the effect of Arg-Gly-Asp peptides on platelet deaggregation was examined. By itself, Gly-Arg-Gly-Asp-Ser-Pro specifically caused dose- and time-dependent deaggregation of platelet aggregates formed by ADP or by thrombin in the presence of 1 mM Gly-Pro-Arg-Pro, but had no effect on the dissociation of thrombin induced platelet-rich fibrin clots. In combination with streptokinase or recombinant tissue-type plasminogen activator, Gly-Arg-Gly-Asp-Ser-Pro enhanced the rate of lysis of platelet-rich fibrin clots. The control Gly-Arg-Gly-Glu-Ser Pro peptide was completely ineffective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762086 TI - Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein. AB - The effects of E4080 [(E)-N-[3-[N'-(2-(3,5-dimethoxyphenyl)ethyl)-N' methyl)amino)propyl]-4- (4-(1H-imidazol-1-yl)phenyl)-3-butenamide dihydrochloride dihydrate] on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (ICa), a transient outward current (ITO), a sustained outward current (ISO) and an oscillatory outward current (IOO), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (Ih). When ICa was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 microM E4080 increased and higher concentrations (10 microM) inhibited ICa, whereas, at the holding potential of -60 mV, E4080 (greater than 1 microM) consistently inhibited ICa, in a concentration-dependent manner. E4080 inhibited ITO, ISO (greater than or equal to 1 microM) and Ih (greater than or equal to 0.1 microM) concentration dependently. Inasmuch as 1 microM E4080 did not inhibit ICa at the holding potential of -80 mV, the inhibition of ITO induced by 1 microM E4080 was not related to the inhibition of ICa. When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 microM) produced a maintained outward current (14.0 +/- 15.3 pA), which was inhibited by glibenclamide. I infinity was inhibited by E4080 (greater than or equal to 0.1 microM) and application of 1 microM glibenclamide partly restored I infinity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762087 TI - Effects of calcitonin gene-related peptide on longitudinal muscle and myenteric plexus of guinea pig ileum. AB - Effects of rat calcitonin gene-related peptide (rCGRP) on the longitudinal muscle myenteric plexus (lm-mp) have been investigated in the present study. rCGRP was shown to have a biphasic effect on the nonstimulated lm-mp, i.e., a transient contraction followed by a longer lasting relaxation. This biphasic action was dose-dependent over the concentration range of 10(-10) to 10(-5) M. Tetrodotoxin (1 microM), atropine (1 microM), 2-chloroadenosine (1 microM) and clonidine (1 microM) inhibited the stimulatory effect. Tetrodotoxin and clonidine also partially inhibited the relaxing effect of rCGRP. This biphasic action of rCGRP was also seen on the contraction of the lm-mp elicited by electrical field stimulation. rCGRP showed only a relaxing effect on the nonstimulated plexus-free longitudinal muscle. rCGRP (2.6 x 10(-10) to 2.6 x 10(-7) M) inhibited both the phasic and tonic contractions induced by histamine in a competitive way and showed a more potent effect on the tonic contraction than that on the phasic contraction. rCGRP at the same dose range also inhibited the tonic but not phasic contraction evoked by membrane depolarization with the maximal stimulation of KCl (30 mM). rCGRP inhibited KCl-, but not histamine-induced, extracellular calcium dependent contraction. The peptide did not affect the dose-response curve of oxotremorine. These results suggest that rCGRP may exert its stimulatory actions on the lm-mp via actions on the plexus nerves, whereas the depressant actions may be mediated via the nerves, as well as directly on the smooth muscle. PMID- 1762088 TI - Stereoselective disposition and metabolism of disopyramide in pediatric patients. AB - Pharmacokinetics of disopyramide (DP) enantiomers was studied in six pediatric patients, 5 to 12 years old, with arrhythmias after i.v. and p.o. administrations of racemic DP. The enantiomers of DP and its active metabolite, mono-N dealkyldisopyramide, in plasma and urine were determined using a chiral, high performance liquid chromatography. Plasma protein binding of DP was measured by ultrafiltration. Because the protein binding of DP was not only concentration dependent but also stereoselective (i.e., S-DP binds to protein more extensively than R-DP), unbound pharmacokinetic parameters were used for evaluating the kinetic behaviors of DP enantiomers. The pediatric age patients had the mean (+/- S.D.) systemic clearance of 15.0 +/- 3.8 and 12.7 +/- 3.9 ml/min/kg for unbound S and R-DP, respectively, which were not only stereoselectively different (P less than .05) but also at least about twice greater than the reported normal adult values. The mean postinfusion elimination half-life values for unbound S- and R DP (2.7 +/- 0.5 and 2.8 +/- 0.4 hr, respectively) in pediatric patients were shorter than those reported from normal adults (approximately equal to 4 to 5 hr). The mean nonrenal (i.e., hepatic) clearance for unbound S- and R-DP (11.1 +/ 4.1 and 8.1 +/- 3.9 ml/min/kg, respectively) were also stereoselectively different (P less than .01) and accounted for approximately equal to 70% of the unbound systemic clearance of the respective enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762089 TI - The new K+ channel opener Aprikalim (RP 52891) reduces experimental infarct size in dogs in the absence of hemodynamic changes. AB - The objective of the present study was to determine the effect of a novel K+ channel opener, Aprikalim (RP 52891; [trans-(-)-N-methyl-2-(3-pyridyl)-2 tetrahydrothio-pyran carbothiamide-1-oxide]), on myocardial infarct size in barbital-anesthetized dogs subjected to 90 min of left circumflex coronary artery occlusion followed by 5 hr of reperfusion. To determine if RP 52891 is mediating its effects by opening adenosine triphosphate regulated potassium channels (KATP), glibenclamide, a KATP channel antagonist was used. Dogs were pretreated with vehicle, a nonhypotensive dose of RP 52891 (10 micrograms/kg + 0.1 microgram/kg/min i.v.), glibenclamide (1 mg/kg; i.v. bolus) or RP 52891 (10 micrograms/kg and 0.1 microgram/kg/min i.v.) after pretreatment with glibenclamide (1 mg/kg i.v. bolus). At the end of reperfusion, myocardial infarct size was determined by triphenyltetrazolium staining. There were no significant differences in systemic hemodynamics, myocardial oxygen demand, collateral blood flow or ischemic bed size among groups with the exception of an increase in coronary blood flow to the ischemic area at 3 and 5 hr of reperfusion in both RP treated groups. However, myocardial infarct size, expressed as a percentage of the area at risk, was significantly (P less than .05) reduced (38%) by RP 52891 and significantly increased (38%) by glibenclamide (vehicle, 39 +/- 4%; RP 52891, 24 +/- 2%; and glibenclamide, 54 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762090 TI - Developmental shift from local to central control of norepinephrine release in the cardiac-sympathetic axis: effects of cocaine and related drugs. AB - Developmental exposure to cocaine is associated with cardiovascular abnormalities as well as neurobehavioral disturbances. Because of the profound influence of cocaine on noradrenergic neurotransmission, we examined its acute effects on norepinephrine release from cardiac nerve terminals in the neonatal rat, as assessed by turnover measurements. Cocaine reduced norepinephrine turnover at all ages studied, but with an apparent transition in the mechanism of action related to the development of central control of sympathetic tone. At 1 day of age, before the establishment of functional connections between the central nervous system and sympathetic neurons, cocaine acted primarily through blockade of norepinephrine reuptake and consequent activation of alpha-2 adrenergic autoreceptors that inhibit transmitter release. Accordingly, its effects were shared by the uptake inhibitor, desmethylimipramine and the alpha-2 agonist, clonidine, but not by drugs whose actions depend upon sympathetic activity or high tonic release of transmitter (yohimbine, pargyline or chlorisondamine). By 21 days, when neuronal activity is under dynamic control by the central nervous system, cocaine was still effective in shutting off norepinephrine release, but the effect was no longer dependent upon blockade of reuptake; desmethylimipramine did not reduce turnover at this age, but clonidine, pargyline and chlorisondamine did. Yohimbine evoked a profound increase in turnover by 21 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762091 TI - Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. AB - Interleukins (ILs) 1 alpha and 1 beta are important components of the neuroimmune axis. Recent work has shown that human 125I-IL-1 alpha can enter the brain from the blood by a saturable system, suggesting a mechanism that may directly link the immune and nervous systems. Here, it is shown that radioiodinated murine IL-1 beta and especially murine IL-1 alpha are even more rapidly transported into the brain of the mouse than is radioiodinated human IL-1 alpha after i.v. injection. All three cytokines exhibited self-inhibition, thus demonstrating saturable transport. Also, they all cross-inhibited the transport of each other. This shows that there are not three separate transport systems, but that they either share transport systems with overlapping affinities or share a single system. It was calculated that 0.06% to 0.08% of the dose of human 125I-IL-1 alpha injected i.v. was present in the brain during the first 60 min. By contrast, no saturable component could be detected in the brain to blood passage of the three ILs. No disruption of the blood-brain barrier to radioactively labeled albumin was found with i.v. doses of up to 50 micrograms/kg of human IL-1 alpha. Additional studies on the blood to brain transport of human 125I-IL-1 alpha showed no modification by dexamethasone, morphine, indomethacin or alpha-melanocyte stimulating hormone. Studies with antibodies directed toward the binding or nonbinding sites of IL or its receptor on the murine T lymphocyte suggest similar, but not identical, structural requirements for transport and for receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762093 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. The Dosimetry System 1986 (DS86) and the Tentative Dosimetry System 1965 (T65D): how do they compare, what is left to do? PMID- 1762092 TI - A temporal window for lateralization of interaural time difference by barn owls. AB - Lateralization of interaural time difference by barn owls (Tyto alba) was studied in a dichotic masking experiment. Sound bursts consisted of two parts: binaurally time-shifted noise, termed the probe, was inserted between masking noise. The owls indicated that they detected and lateralized the time-shift in the probe by a head turn in the direction predicted from sign of the time-shift. The general characteristics of head turns in response to this stimulus was similar to the head turns elicited by free-field stimulation or to head turns in response to presentation of the probe alone. The owls could easily lateralize stimuli containing long probes. The number of correct turns decreased as probe duration decreased, demonstrating that the masking noise interfered with the owls' ability to lateralize the probe. The minimal probe duration that the animals could lateralize ("minimal duration") became shorter as burst duration decreased. Minimal duration ranged from 1 ms to 15 ms for the two subjects and burst durations from 10 to 100 ms. These findings suggested that owls possess a temporal window. A fitting procedure proposed by Moore et al. (1988) was used to determine the shape of the temporal window. The fitting procedure showed that the shape of the owls' binaural temporal window could be described by the same algorithms as the human monaural temporal window. Thus, the temporal window is composed of a short time constant that determines the central part of the window, and a longer time constant that determines the shape at the skirts of the window. PMID- 1762094 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. PMID- 1762095 TI - Recalculation of data on 32P activity induced in sulfur in Hiroshima. AB - Historical data for 32P activity induced in sulfur by fast neutrons have been corrected for decay with a recent half-life value of 32P and recalculated with an experimentally determined efficiency ratio of the electroscope for beta rays from 32P and natural uranium used as a standard. Most samples would have been pure enough so that no correction for the weight of sulfur has been made. The possibility of interference with 32P activity measurements due to induced activity of other elements in the samples could also be excluded. The revised data show little difference from the original ones except for one sample which contained much impurity. Uncertainty of the data was also discussed. PMID- 1762096 TI - Allowing for dose-estimation errors for the A-bomb survivor data. AB - Unless allowances are made, random errors in radiation dose estimates cause underestimation of linear risk estimates and distort the shape of dose-response curves. These errors also result in spurious associations between radiogenic endpoints, exaggerating possible variations in individual sensitivity to radiation. Statistical methods have been developed which reduce these biases, based on assumptions regarding the nature and magnitude of dose-estimation errors. Some understanding of the underlying statistical basis for these methods is necessary to both those interested in interpreting radiogenic effects and those interested in the dosimetry system. This paper discusses the basic statistical issues and their implications, presents some statistical methods to deal with the problem, and indicates the sensitivity of certain results to assumptions about the magnitude of the dose-estimation errors. PMID- 1762097 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Theoretical background of the Dosimetry System 86 (D586). AB - DS86 is a calculation code system for the estimation of the radiation dose of atomic bomb survivors at Hiroshima and Nagasaki. The DS86 calculation process is as follows: 1. Compute free-field radiation environment: radiation transport calculation can be done for the free air field at Hiroshima and Nagasaki. 2. Compute shielded radiation environment: depending on each shielding situation, the shielding can be calculated by using either the Nine-Shielding Parameter or the Globe Shielding Data. 3. Compute radiation environment at the organ site: organ kerma and fluence spectra can be calculated using a transport calculation code depending on each survivor sex, age, orientation and posture. PMID- 1762098 TI - Recent uses of biological data for the evaluation of A-bomb radiation dosimetry. AB - Random errors in the DS86 radiation dose estimates used in the analysis of A-bomb survivor data are recognized to have an important impact upon estimates of the risk of late effects such as cancer. Little however is known for certain concerning the distribution of such random errors. This paper gives an overview of recent work at the Radiation Effects Research Foundation (RERF) using multivariate analysis of biological data, including acute effects of radiation exposure, late effects (eg leukemia mortality) and stable chromosome aberrations, for the purpose of evaluating the extent of random error in the estimation of individual doses using DS86. The emphasis here is on analyses of apparent association between biological endpoints, in light of a dosimetry error model framework proposed recently by Pierce et al. Analyses performed to date appear to be consistent with the view that lognormal random dosimetry errors with a standard deviation of 40% or greater of true dose may exist in DS86. Association between radiogenic outcomes in A-bomb survivors, after adjustment for DS86 estimated dose level, has been detected for such widely varying pairs of outcomes as mutant T-cell frequencies and chromosome aberrations, epilation and leukemia mortality, and epilation and chromosome aberrations. The motivation for examining association between pairs of biological endpoints has usually been to determine the extent to which radiation sensitivity varies between individual survivors. Recognizing, however, that random error in dose estimates results in apparent association between biological outcomes is crucial to interpreting studies, such as these, which use data on multiple biological endpoints. To go one step further, in situations where there is a prior knowledge about the biological plausibility of such associations in outcome data the amount of association between radiogenic outcomes (remaining after adjustment for estimated dose), to the extent that they are greater than that assumed to be reasonable, is an important potential source of information concerning the magnitude of random errors in the DS86 dose estimates. PMID- 1762099 TI - Medical X-ray doses' contributions to the ionizing radiation exposures of atomic bomb survivors. AB - Doses from diagnostic radiological examinations were measured in order to evaluate the radiation risks of atomic-bomb survivors in Hiroshima and Nagasaki. Using a phantom human, doses to the active bone marrow, gonads, salivary glands, thyroid gland, lung, breast, stomach and colon were determined by type of examination and by examination site. The results of this dosimetry program will aid in estimating the diagnostic exposure doses received by each participant in the Adult Health Study of the Radiation Effects Research Foundation. The current results of these dosimetry studies also indicate that the effects of A-bomb exposure cannot be reliably assessed unless medical X-ray doses are carefully incorporated into these long-term evaluations. PMID- 1762100 TI - The LD50 associated with exposure to the atomic bombing of Hiroshima and Nagasaki. AB - Numerous attempts have been made to estimate the distance at which 50% of the individuals exposed to the A-bombing of Hiroshima and Nagasaki died, ostensibly from their exposure to ionizing radiation. It is difficult to convert most of these distance estimates to a dose-related LD50, since radiation shielding was ignored. The recent reassessment of the atomic bomb radiation dosimetry has provided an opportunity for the estimation of the bone marrow LD50. There is a surprising concordance in the various estimates that have been made given the different groups of survivors involved and the methods used to estimate the LD50/60. PMID- 1762101 TI - Atomic bomb and leukemia. AB - Characteristic features of leukemia among atomic bomb survivors were studied. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic for atomic bomb radiation induced leukemia. In the distribution of AML subtypes of FAB classification, there was no M3 cases in 1Gy or more group, although several atypical AML cases of survivors were observed. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral blood of proximal survivors. PMID- 1762102 TI - Multiple myeloma among atomic bomb survivors. PMID- 1762103 TI - Cytogenetic and molecular changes in leukemia found among atomic bomb survivors. AB - Seventy five radiation-related leukemias (acute non-lymphocyte) in Hiroshima including 16 patients exposed to more than one Gray were cytogenetically examined. Statistical analysis of the data on the frequencies of chromosomal aberrations in survivors according to the bone marrow doses of DS86 estimation revealed that heavily exposed patients tended to have significantly higher aberration rates as compared with non-exposed patients. Furthermore, the chromosomal aberrations in the survivors were observed to be of a more complex nature and had characteristic findings of secondary leukemia. These observations therefore suggest that patients with a history of heavy exposure to atomic bomb radiation exhibit leukemic cells that originated from a stem cell which had been damaged by irradiation at the time of bombing and had been involved in the complex chromosome abnormalities. Molecular biological studies on transforming genes in acute and chronic leukemia and the bcr gene in chronic myelocytic leukemia have been performed in exposed and non-exposed groups. So far, no distinctive differences have been observed in the frequency and the sites of point mutations in N- and K-ras genes or in the rearrangement of the bcr gene, for a final conclusion of the specificity of radiation induced leukemia. Further retrospective studies require patient DNAs that developed in the early period of the atomic bomb exposure. PMID- 1762104 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Thyroid cancer: reports up to date and a review. AB - Evidence to date from a number of studies, indicates that there is an increased incidence of thyroid cancer among A-bomb survivors, and that the incidence rises with increase of dose and is especially predominant in females exposed at younger ages. Although 45 years have elapsed since A-bomb exposure, there are still some questions about the development of thyroid cancer: 1) Is the incidence now decreasing? 2) What factors, other than radiation exposure, are involved? 3) What is the incidence of multiple cancer, including thyroid cancer? With these questions in mind, it is apparent that studies in this field must continue for some time to come. PMID- 1762105 TI - Parathyroid tumors in atomic bomb survivors in Hiroshima: a review. AB - Parathyroid tumors in A-bomb survivors in Hiroshima have been studied. Thirteen cases of parathyroid tumor were confirmed from 4,136 autopsy cases between 1961 to 1977, and an elevated incidence of tumor with increase of dose (T65D) was demonstrated (P less than 0.01). A high proportion of 42.9%, 6 out of 14 parathyroid tumors extirpated at Hiroshima University Hospital between 1956 and 1988, were atomic bomb survivors exposed within 4.1 km from the hypocenter. From an epidemiological study using 23 parathyroid tumor cases detected in Hiroshima Prefecture between 1974 and 1987, an elevated incidence of parathyroid tumors with increase of dose (proximally exposed, other exposed and control nonexposed) was demonstrated (P less than 0.001). PMID- 1762106 TI - Thyroid cancer: epidemiological study of thyroid cancer in A-bomb survivors from extended life span study cohort in Hiroshima. AB - We analysed thyroid cancers which were diagnosed clinically or detected at autopsy during 22 years (1958 to 1979) in a sample of 75,493 study subjects exposed in Hiroshima belonging to the extended LSS sample of the Radiation Effects Research Foundation. One hundred and twenty-five cases of clinical thyroid cancer (15 in males and 110 in females) were confirmed, giving a crude incidence rate per 100,000 person-years of 2.7 for males, 12.4 for females and 8.6 for both sexes combined. There was a significant increase of thyroid cancer with increase of atomic bomb radiation dose (thyroid tissue dose based on T65D) in females and in the sexes combined. This tendency was predominant in those exposed at less than 19 years of age. Compared to the control group, the relative risk in the greater than or equal to 0.50 Gy group was higher at 4.0 for males (not significant) and at 4.3 for females (p less than 0.01). Latent thyroid cancer was detected in 155 cases or 3.5% (2.5% for males and 4.5% for females) of the 4,425 cases that came to autopsy during the same period. Compared to the control group, the relative risk in the 50+ rad group was 1.7 for males (not significant), 2.0 for females (p less than 0.05) and 1.9 for both sexes combined (p less than 0.05). New data obtained from autopsy cases between 1950 and 1985 have been added. PMID- 1762107 TI - Studies of radioactivity produced by the Hiroshima atomic bomb: 1. Neutron induced radioactivity measurements for dose evaluation. AB - This review summarizes measurements made of 152Eu and 60Co radioactivity induced by neutron radiation from the Hiroshima atomic bomb (A-bomb) with the goal of estimating the neutron dose released by the bomb. Prior to these measurements, A bomb-irradiated specimens such as rocks and pieces of concrete, which had not been shielded were collected. The specific radioactivity obtained (in bequerels per gram of Eu or Co) were compared with those calculated from DS86 neutrons. Findings of usefulness of 152Eu data within 700 m ground range are reported and systematic differences between measured activities and calculations are discussed. The 152Eu data were also useful for the discussion of circular asymmetry, and there was no asymmetry within the experimental errors. This review also covers the similar difference found in 32P data, which were measured immediately after the A-bomb, along with the other 152Eu and 60Co data. The need for more measurements of 152Eu activity in samples farther away from the hypocenter in order to verify the DS86 calculations is also discussed. PMID- 1762108 TI - Follow-up studies of breast cancer incidence among atomic bomb survivors. PMID- 1762109 TI - Mortality among atomic bomb survivors. AB - The Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, have conducted a long-term follow-up study of a cohort of 120,000 atomic bomb survivors and non-exposed controls since 1950. The most recent findings regarding cancer mortality during the period 1950-85 in this cohort, based on the DS86 doses are as follows: 1) The dosimetry change does not alter the list of radiation-related cancers. Some city differences in dose response previously thought to be real are no longer significant with the DS86 doses. Assuming a linear dose-response, and using estimated organ-absorbed doses, the risk coefficients derived from the two dosimetries are very similar. If larger RBE values are assumed, the disparity between the two dosimetries increases because the neutron dose is much greater in the T65 dosimetry. 2) Besides the well-known increase of leukemia, there also have been demonstrated increases in cancers of the lung, breast, esophagus, stomach, colon, ovary, urinary bladder, and of multiple myeloma, but no increase has yet been observed in mortality from cancer of the rectum, gallbladder, pancreas, prostate and uterus, and of malignant lymphoma. In general, radiation-induced solid cancer begins to appear after attaining the age at which the cancer is normally prone to develop (the so-called "cancer age"), and continues to increase proportionately with the increase in mortality in the control group as it ages. Sensitivity to radiation, in terms of cancer induction, is higher generally for persons who were young at the time of the bomb (ATB) than for those who were older ATB. Non-cancer mortality in the period 1950-78, based on the T65 doses, which is the most recent published report, did not show an increase with dose, but now, with the accumulation of seven more years of follow-up, there seems to be an excess in the very high dose range, particularly for the younger age ATB cohort. Further follow up is called for to confirm this suggestion. PMID- 1762110 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Cancer risk among in utero-exposed survivors. AB - The Radiation Effects Research Foundation (RERF) continues to conduct a follow-up study initiated some years ago of cancer mortality and incidence among the survivors of the atomic bombing of Hiroshima and Nagasaki exposed in utero. Although only 18 incident cases of cancer were identified in the years 1950-1984 (of which 5 cases were in the 0 dose group), cancer risk appears to increase significantly as maternal uterine dose increases. Only two cases of childhood cancer were observed among these individuals in the first 14 years of life; both had been exposed to greater than or equal to 0.30 Gy. All other cases developed cancer in adulthood, and the cancers they developed are, in the main, the ones known to be elevated in frequency among the postnatally exposed survivors. The estimated relative risk for cancer at 1 Gy (uterine dose) is 3.77. The results suggest that the in utero group may have a higher risk than that seen among exposed adults because the individuals exposed in utero have not reached the major cancer prone age. However, since the observed cases are too few to allow a site-specific review, further follow-up studies are required to determine if the observed increased cancer risk can definitely be attributed to A-bomb radiation, although there appears to be a significant dose-related cancer response. PMID- 1762111 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Tumor registries and cancer incidence studies. AB - A tumor registry is essential in the systematic collection and analysis of tumor data in a defined population. Population-based tumor registries have been in operation for more than 30 years in Hiroshima and Nagasaki. While the tumor registry data have previously been used for many site-specific cancer studies in atomic bomb survivors, overall analysis of tumor registry based cancer incidence data among the atomic bomb survivors has not been undertaken for some time. However, a recent improvement in the tumor registries has made it possible to analyze most recent cancer incidence data among the Life Span Study population. Preliminary analysis under way indicates a potential power of the data. There are a few methodological problems associated with the use of the incidence data, especially relating to consistency of data and migration. Several measures taken to resolve such problems are discussed. PMID- 1762112 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Hyperparathyroidism. AB - An epidemiological survey on hyperparathyroidism (HPT) among A-bomb survivors in Hiroshima has been conducted since August 1986. The results are summarized based on proceedings of meetings. The survey demonstrated that the prevalence rate of HPT increased with A-bomb radiation dose. Further analysis is now under way on the relationship between HPT prevalence and radiation dose, sex and age, the results of which will be published in the near future. PMID- 1762114 TI - Persistent chromosome aberrations in the somatic cells of A-bomb survivors, Hiroshima and Nagasaki. AB - Current status of knowledge on the radiation-induced chromosome aberrations persisting since their induction in 1945 to date in the somatic cells of A-bomb survivors in Hiroshima and Nagasaki is reviewed. Dose-response relationship for chromosome aberration frequencies observed with the use of the old A-bomb dosimetry system (T65D) is also demonstrable based on the new dosimetry system (DS86). Despite the fact that the remarkable decrease in the amount of neutron component relative to the total dose in Hiroshima, there still exist inter-city differences in aberration frequency per unit dose both for kerma and bone marrow dose; the dose-square term is smaller in Hiroshima than in Nagasaki. The differential contribution of neutron radiation may be responsible in some part for the observed difference between Hiroshima and Nagasaki, although proof still remains to be obtained. There is a wide variability of the frequency of cells with chromosome aberrations between survivors within a given dose range. Random errors in the dose estimates assigned to individual survivors seem responsible, to a large extent, for the observed overdispersions in aberration frequencies in both cities. New molecular biology-oriented techniques to differentially stain specific chromosomes using fluorescence in situ hybridization with chromosome specific composite DNA probes seem extremely promising for future rapid, accurate and extensive screening of reciprocal translocations observed predominantly in A bomb survivors. Such data may be utilized to establish a better biological dosimetry system, especially for those persons who are irradiated in vivo many years before cytogenetic examinations. PMID- 1762113 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Brain damage among the prenatally exposed. AB - Significant effects on the developing brain of exposure to ionizing radiation are seen among those individuals exposed in the 8th through the 25th week after fertilization. These effects, particularly in the most sensitive period, 8-15 weeks after fertilization, manifest themselves as an increased frequency of severe mental retardation (SMR), a diminution in IQ score and in school performance, and an increase in the occurrence of seizures. Of 30 SMR cases, 18 (60%) had small heads. About 10% of the individuals with small head sizes observed among the in utero clinical sample were mentally retarded. When all of the cases of mental retardation are included in the analysis, a linear dose response model fits the data adequately and no evidence of a threshold emerges; however, if the two probable nonradiation-related cases of Down's syndrome are excluded from the 19 SMR cases exposed 8-15 weeks after fertilization, the evidence of a threshold is stronger. The 95% lower bound of the threshold based on the new dosimetry system appears to be in the range of 0.12-0.23 Gy. In the 16 25 week period, the 95% lower bound of the threshold is 0.21 Gy both with and without inclusion of two probable nonradiation-related retarded cases. In a regression analysis of IQ scores and school performance data, a greater linearity is suggested with the new dosimetry (DS86) than with the old (T65DR), but the mean IQ score and the mean school performance of those exposed in utero to doses under 0.10 Gy are similar, and not statistically different from the means in the control group. The risk ratios for unprovoked seizures, following exposure during the 8th through the 15th week after fertilization, are 4.4 (90% confidence interval: 0.5-40.9) after 0.10-0.49 Gy and 24.9 (4.1-191.6) after 0.50 Gy or more when the mentally retarded are included and 4.4 (0.5-40.9) and 14.5 (0.4-199.6), respectively, when they are excluded. PMID- 1762115 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Chromosome abnormality in early entrants. AB - A preliminary study was performed to estimate radiation dose in 10 individuals who had entered Hiroshima city one day after the explosion and worked around the hypocenter area for a week. The numbers of cells with chromosome aberrations differed in each subject, ranging from one to 18 (median: 11 abnormalities) in 500 metaphases of lymphocytes cultured for 48 hours with Phytohemagglutinin. Five individuals had more than 1.6 percent stable type aberrations and were estimated to have been exposed to 6-13 rad. The other five individuals and the controls were estimated to be less than two rad. PMID- 1762116 TI - Somatic cell mutations in atomic bomb survivors. AB - Mutant frequencies in peripheral blood lymphocytes and erythrocytes have been measured for atomic bomb survivors having various DS86 doses. Among the four assay systems utilized so far, erythrocyte glycophorin A assay revealed a dose related increase of mutant frequency, similar to the results obtained with in vitro mutagenesis studies at HPRT locus using human diploid cells. Mutant T lymphocyte frequency of the HPRT locus detected as resistant to 6-thioguanine significantly increased with DS86 dose however the slope was very shallow compared with that of in vitro study. Mutation at T-cell receptor genes and the HLA-A gene did not show a significant increase in frequency with dose in cells of survivors studied. PMID- 1762117 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Radiation cataract. AB - This report reviews the relationship of ionizing radiation to the occurrence of cataracts (posterior lenticular opacities) among the A-bomb survivors in Hiroshima and Nagasaki. The new DS86 doses are available for 1,983 (93.4%) of the 2,124 A-bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima is much smaller than its comparable T65DR component, but still 4.2 fold higher (0.38 Gy at 6 Gy) than that in Nagasaki (0.09 Gy at 6 Gy). Thus, if the eye is especially sensitive to neutrons, there may yet be some useful information on their effects, particularly in Hiroshima. Under the best fitting dose-response model, an L(gamma)-L(neutron) with two thresholds, both the gamma and neutron regression coefficients of the occurrence of cataracts on dose are positive and highly significant for the DS86 eye organ doses. The DS86 gamma coefficient is almost the same as that associated with the T65DR gamma dose, the ratio of the two coefficients being 1.1 (95% confidence limits: 0.5-2.3) for DS86 kerma in the individual dose data, and if the risks based on the DS86 eye organ dose and DS86 kerma are compared, the ratio is 1.3 (0.6-2.8). However, the risk estimates associated with neutron exposure are 6.4 (2.2-19.2) fold higher for the DS86 kerma than the T65DR kerma and 1.6 (0.5-2.3) fold higher for the DS86 eye organ dose than for the DS86 kerma. PMID- 1762118 TI - Mortality and cancer risk among the offspring (F1) of atomic bomb survivors. AB - The Atomic Bomb Casualty Commission (ABCC) and its successor Radiation Effect Research Foundation (RERF) has over the years conducted many studies to determine possible genetic effects of atomic bomb radiation among the offspring of atomic bomb survivors. Findings concerning mortality and cancer incidence of the offspring are summarized in this chapter. PMID- 1762119 TI - Overview of immunological studies on A-bomb survivors. AB - Among the peripheral blood lymphocytes, T-cells and B-cells significantly decreased in number with age. Radiation exposure resulted in further significant decrease of T-cell count (but not B cells) in the elderly. T-cell response to PHA and allo-antigens also decreased with dose in the elderly group. In contrast, NK cell number and function increased with age while a significant dose effect was not observed. PMID- 1762120 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Aging. AB - The hypothesis that exposure to ionizing radiation accelerates the aging process has been actively investigated at ABCC-RERF since 1958, when longitudinal cohort studies of the Adult Health Study (AHS) and the Life Span Study (LSS) were initiated. In their 1975 overall review of aging studies related to the atomic bomb (A-bomb) survivors, Finch and Beebe concluded that while most studies had shown no correlation between aging and radiation exposure, they had not involved the large numbers of subjects required to provide strong evidence for or against the hypothesis. Extending LSS mortality data up to 1978 did not alter the earlier conclusion that any observed life-shortening was associated primarily with cancer induction rather than with any nonspecific cause. The results of aging studies conducted during the intervening 15 years using data from the same populations are reviewed in the present paper. Using clinical, epidemiological, and laboratory techniques, a broad spectrum of aging parameters have been studied, such as postmortem morphological changes, tests of functional capacity, physical tests and measurements, laboratory tests, tissue changes, and morbidity. With respect to the aging process, the overall results have not been consistent and are generally thought to show no relation to radiation exposure. Although some preliminary results suggest a possible radiation-induced increase in atherosclerotic diseases and acceleration of aging in the T cell-related immune system, further study is necessary to confirm these findings. In the future, applying the latest gerontological study techniques to data collected from subjects exposed 45 years ago to A-bomb radiation at relatively young ages will present a new body of data relevant to the study of late radiation effects. PMID- 1762121 TI - Studies of radioactivity produced by the Hiroshima atomic bomb: 2. Measurements of fallout radioactivity. AB - Three studies of fallout measurements were reviewed for the discussion of possible radioactivity intake from the Hiroshima atomic bomb. The first study discussed correlations between enriched 234U and 137Cs specific activities from the measurement of soil samples collected in the "black rain" area. The second study measured 137Cs activity on the rock and roof tile samples collected in the hypocenter area immediately after the explosion. Some of the rock and roof tile samples collected near the hypocenter had a small but detectable amount of 137Cs activity. However, it has been determined that 137Cs exposure, for example, was negligible compared with DS86 dose estimates, since these activity levels were low. The third study detected 90Sr activity in some of the specimens of human bones exhumed on Ninoshima Island. This study compared the difference in activity between the bone head and shaft, with higher activities obtained in the bone head. This fact suggests a short intake period for this activity, however, the levels of 90Sr contamination were too low to allow a discussion of the exposure risks. PMID- 1762122 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Current summary of lymphocyte survival study. AB - A recently developed dose-survival assay in vitro using human G0 T-lymphocytes from peripheral blood was employed to assess possible interindividual variation of cellular radiosensitivity. Currently lymphocytes from a total of 99 atomic bomb survivors were tested and D10, the X-ray dose required to kill 90% of the cells, was calculated for each test. The mean +/- SD of D10 value was 3.35 +/- 0.22 Gy for 61 survivors whose DS86 dose is below 0.004 Gy and for 38 survivors of DS86 dose above 1.5 Gy it was 3.31 +/- 0.26 Gy. So far, the results do not show any evidence in support of the hypothesis of a selective elimination of a radiosensitive subcohort among the survivors exposed to high doses. PMID- 1762123 TI - X-ray sensitivity of fibroblast cell strains derived from atomic bomb survivors with and without breast cancer. AB - Fibroblasts were established in vitro from skin biopsies obtained from 55 women and 1 man with or without breast cancer and with or without exposure to radiations from the atomic bomb (A-bomb) explosion in Hiroshima. The radiosensitivity of these cells was evaluated by clonogenic assays after exposure to X-rays. Dose-response curves were fitted to a multitarget model, S/S0 = A[1-(1 e-D/D0)N]. There was no difference in the means or variances of radiosensitivity between exposed and nonexposed groups, or between groups with and without breast cancer. PMID- 1762124 TI - Interactive effects between radiation and other factors on cancer risk among A bomb survivors--an overview of RERF studies. AB - This paper reviews RERF cancer studies conducted to examine interactive effects between radiation and epidemiological risk factors, including smoking habits, occupation, dietary habits and OB/GYN history. Special emphasis is placed on a review of studies of interactive effects between cigarette smoking and radiation on lung cancer risk. Comments on these studies are made and proposals for future studies are presented. PMID- 1762125 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Future research in epidemiology and statistics at RERF. PMID- 1762126 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Biochemical genetics study. AB - After 40 years of studies on the children of atomic bomb survivors and a suitable control population in which no statistically significant genetic effects of A bomb radiation were observed, two new projects have been initiated in order to detect mutations in the DNA and RNA molecules. Permanent cell lines from peripheral B-lymphocytes from approximately 500 families composed of exposed parents and their children and approximately 500 control families are being established by Epstein-Barr virus transformation. Cells will be sources for DNA and RNA samples in the screening for mutations. After comparison of efficiencies of the scanning techniques, we selected the denaturing gradient gel electrophoresis (DGGE) of DNA fragments amplified by polymerase chain reaction (PCR) for our purpose. A small scale pilot study has started to solve problems and obtain a better efficiency in this approach. Current thinking about the most efficient procedures is presented. PMID- 1762127 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Future studies of the prenatally exposed survivors. PMID- 1762128 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Future perspective of radiobiological studies. PMID- 1762129 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Summary and conclusions. PMID- 1762130 TI - Reassessment of gamma-ray doses in Hiroshima and Nagasaki. AB - Reassessment of gamma-ray doses from the atomic bombs in Hiroshima and Nagasaki has been carried out with the thermoluminescent measurements of bricks and decorative tiles which were collected from the buildings that remain as they were at the time of the explosions. The thermoluminescent measurements were performed using a dating technique generally used in archaeology. Annual background dose rates from natural radionuclides in the brick and tile samples and from environmental radiations around the samples were determined with commercially available thermoluminescent detectors. The resultant gamma-ray doses in Hiroshima and Nagasaki are given as a function of distance from the hypocenters and are compared with the DS86 (Dosimetry System 1986) and the T65D (Tentative 1965 Dose). PMID- 1762131 TI - Thermoluminescence dosimetry of gamma rays using ceramic samples from Hiroshima and Nagasaki: a comparison with DS86 estimates. AB - This study reports gamma-ray doses measured using thermoluminescence (TL) dosimetry of atomic-bomb-exposed ceramic samples from Hiroshima and Nagasaki. Advances in the dosimetry of TL-sensitive minerals in the field of TL dating of archaeological and geological materials made it possible to measure a radiation dose of 10(-2) Gy. Ceramic samples such as tiles and bricks were collected from locations between 523 and 2,453 m from the hypocenter in Hiroshima and from between 731 and 1,565 m in Nagasaki. The gamma-ray dose estimates derived from these samples are compared with estimates from DS86. A significant discrepancy was noted between the doses measured for samples from Hiroshima and DS86 values. One possible cause of this discrepancy might be a secondary gamma-ray dose related to the neutron dose. PMID- 1762132 TI - A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Residual radioactivity in neutron-exposed objects and residual alpha radioactivity in black rain areas. AB - The residual Eu-142 radioactivity due to the atomic bomb explosion in 1945 was first found in 1976 by in-situ high resolution gamma-ray spectrometry at Hiroshima. Since then, various studies on this nuclide have continued not only in Hiroshima but also in Nagasaki and they have contributed to the reevaluation of the neutron dose due to the A-bombing. By radiochemical separation methods and alpha-ray spectrometry, rather high levels of plutonium were found in the surface soil and in the bottom sediment of water reservoir which were collected at "Black rain area" in Nagasaki. The U-234/U-238 activity ratios for the uranium leached with 0.1 HNO3 from the surface of soil samples were found to be relatively higher for the samples which were collected at "Black rain area" in Hiroshima. PMID- 1762133 TI - Residual neutron-induced radionuclides in samples exposed to the nuclear explosion over Hiroshima: comparison of the measured values with calculated values. AB - Residual radionuclides induced by neutrons from the Hiroshima atomic bomb have been measured at Kanazawa University for 14 years. The results of 152Eu, 154Eu and 60Co are reviewed in this paper. Where appropriate, an attempt is made to provide our new data with the aim of reinterpreting our published data. From the comparison of the measured values with the calculated values by DS86 methodology, we may point out here: (1) that close agreement was found between measured and calculated values for the specific radioactivity of 152Eu in the samples exposed at ground ranges between 320 m and 720 m; (2) that the calculated/measured ratios for the specific radioactivity of 152Eu were, however, larger than unity in the vicinity of ground zero and smaller than unity at locations more than 1000 m apart from ground zero; (3) that, in the vicinity of ground zero, epithermal neutron fluence evaluated from a set of measured specific radioactivities of 152Eu, 154Eu and 60Co showed a close agreement with the calculated result, whereas thermal neutron fluence evaluated in the same way was different from the calculated result; and (4) that the depth distribution of the specific radioactivity of 152Eu in a wall sample which was exposed at the location 320m from ground zero approximately agreed with the calculated result. PMID- 1762135 TI - A research agenda for dental public health. PMID- 1762134 TI - Determination of 60Co activity in steel samples in Hiroshima. AB - Specific activity of 60C in two steel samples taken at 687m S and 1295m NNW from the hypocenter was measured by gamma-ray spectrometry and neutron activation analysis. The results are consistent with previous data by Hashizume et al. for steel rings on the surface of roofs of buildings. content of nickel and copper in the samples was found to be too small to account for any significant 60Co production by fast neutron reactions. PMID- 1762137 TI - Research in prevention of oral diseases and conditions. PMID- 1762136 TI - Epidemiologic investigations. PMID- 1762138 TI - Research on oral health education and promotion and social epidemiology. PMID- 1762139 TI - Health services research in dental public health. PMID- 1762140 TI - Implementation of the research agenda. PMID- 1762141 TI - A research agenda for dental public health--rationale and development. PMID- 1762142 TI - Specific protein phosphorylation occurs in molluscan red blood cell ghosts in response to hypoosmotic stress. AB - The regulation of cellular volume upon exposure to hypoosmotic stress is accomplished by specific plasma membrane permeability changes that allow the efflux of certain intracellular solutes (osmolytes). The mechanism of this membrane permeability regulation is not understood; however, previous data implicate Ca2+ as an important component in the response. The regulation of protein phosphorylation is a pervasive aspect of cellular physiology that is often Ca2+ dependent. Therefore, we tested for osmotically induced protein phosphorylation as a possible mechanism by which Ca2+ may mediate osmotically dependent osmolyte efflux. We have found a rapid increase in 32Pi incorporation into two proteins in clam blood cell ghosts after exposure of the intact cells to a hypoosmotic medium. The osmotic component of the stress, not the ionic dilution, was the stimulus for the phosphorylations. The osmotically induced phosphorylation of both proteins was significantly inhibited when Ca2+ was omitted from the medium, or by the calmodulin antagonist, chlorpromazine. These results correlate temporally with cell volume recovery and osmolyte (specifically free amino acid) efflux. The two proteins that become phosphorylated in response to hypoosmotic stress may be involved in the regulation of plasma membrane permeability to organic solutes, and thus, contribute to hypoosmotic cell volume regulation. PMID- 1762143 TI - Generalized protein tertiary structure recognition using associative memory Hamiltonians. AB - In previous papers, a method of protein tertiary structure recognition was described based on the construction of an associative memory Hamiltonian, which encoded the amino acid sequence and the C alpha co-ordinates of a set of database proteins. Using molecular dynamics with simulated annealing, the ability of the Hamiltonian to successfully recall the structure of a protein in the memory database was successfully demonstrated, as long as the total number of database proteins did not exceed a characteristic value, called the capacity of the Hamiltonian, equal to 0.5N to 0.7N, where N is the number of amino acid residues in the protein to be recalled. In this paper, we describe the development of additional methods to increase the capacity of the Hamiltonian, including use of a more complete representation of the protein backbone and the incorporation of contextual information into the Hamiltonian through the use of secondary structure prediction. In addition, we further extend the ability of associative memory models to predict the tertiary structures of proteins not present in the protein data set, by making the Hamiltonian invariant with respect to biological symmetries that represent site mutations and insertions and deletions. The ability of the Hamiltonian to generalize from homologous proteins to an unknown protein in the presence of other unrelated proteins in the data set is demonstrated. PMID- 1762144 TI - Solution structure of the tissue-type plasminogen activator kringle 2 domain complexed to 6-aminohexanoic acid an antifibrinolytic drug. AB - The solution structure of a recombinant tissue-type plasminogen activator kringle 2 domain, complexed with the antifibrinolytic drug 6-aminohexanoic acid (6-AHA) was determined via 1H nuclear magnetic resonance spectroscopy and dynamical simulated annealing calculations. The structure determination is based on 610 intramolecular kringle 2 and 14 intermolecular kringle 2-6-AHA interproton distance restraints, as well as on 82 torsion angle restraints. Three sets of simulated annealing structures were computed from three different classes of starting structures: (1) random conformations devoid of disulfide bridges; (2) random conformations that contain correct disulfide bonds; and (3) a folded conformation modeled after the homologous prothrombin kringle 1 X-ray crystallographic structure. All three sets of structures are well defined, with averaged atomic root-mean-square deviations between individual structures and mean set structures of 0.77, 0.99 and 0.70 A for backbone atoms, and 1.36, 1.55 and 1.41 A for all atoms, respectively. Kringle 2 is an oblate ellipsoid with overall dimensions of approximately 34 A x 30 A x 17 A. It exhibits a compact globular conformation characterized by a number of turns and loop elements as well as by one right-handed alpha-helix and five (1 extended and 4 rudimentary) antiparallel beta-sheets. The extended beta-sheet exhibits a right-handed twist. Close van der Waals' contacts between the Cys22-Cys63 and Cys51-Cys75 disulfide bridges and the central hydrophobic core composed of the Trp25, Leu46, His48a and Trp62 side-chains are among the distinguishing features of the kringle 2 fold. The binding site for 6-AHA appears as a rather exposed cleft with a negatively charged locus defined by the Asp55 and Asp57 side-chains, and with an aromatic pocket structured by the Tyr36, Trp62, His64 and Trp72 side-chains. The Trp62 and His64 rings line the back surface of the pocket, while the Tyr36 and Trp72 rings confine it from two sides. The Trp62 and Trp72 indole rings conform a V-shaped groove. The methyl groups of Val35 also contribute lipophilic character to the ligand-interacting surface. It is suggested that the positively charged side chains of Lys34 and, potentially, Arg69 may favor interactions with the carboxylate group of the ligand. The Trp25 and Tyr74 aromatic rings, although conserved elements of the binding site structure, seem not to undergo direct contacts with the ligand. PMID- 1762145 TI - Three-dimensional model for stellacyanin, a "blue" copper-protein. AB - A three-dimensional model of the "blue" copper-glycoprotein stellacyanin from Rhus vernicifera has been derived by computer graphics, energy minimization and molecular dynamics techniques. The initial atomic co-ordinates were obtained by making substitutions and insertions in the known structure of another blue copper protein, cucumber basic protein (CBP), which is 46% homologous with stellacyanin and has similar spectroscopic properties. An important difference between CBP and stellacyanin is that the latter lacks methionine, a residue that forms an exceptionally long bond to the copper atom in all blue copper-proteins of known structure. In the aligned amino acid sequences, stellacyanin has glutamine 97 at the position that corresponds to the copper-binding methionine 89 in CBP. The hypothesis that the copper atom in stellacyanin is co-ordinated by the side-chain functional groups of histidine 46, cysteine 87, histidine 92 and glutamine 97 leads to a model that enables the spectroscopic properties, redox potential and electron-transfer kinetics of the protein to be rationalized. The present model for stellacyanin is more plausible than an antecedent model derived from the structure of plastocyanin. This demonstrates that the output from molecular modeling calculations is strongly dependent on the input, and that sequence homology with the target molecule is an important criterion for the selection of a starting model. PMID- 1762146 TI - High resolution structure of an oligomeric eye lens beta-crystallin. Loops, arches, linkers and interfaces in beta B2 dimer compared to a monomeric gamma crystallin. AB - beta-Crystallins are polydisperse, oligomeric structural proteins that have a major role in forming the high refractive index of the eye lens. Using single crystal X-ray crystallography with molecular replacement, the structure of beta B2 dimer has been solved at 2.1 A resolution. Each subunit comprises an N and C terminal domain that are very similar and each domain is formed from two similar "Greek key" motifs related by a local dyad. Sequence differences in the internally quadruplicated molecules, analysed in terms of their beta-sheets, hairpins and arches, give rise to structural differences in the motifs. Whereas the related family of gamma-crystallins are monomers, beta-crystallins are always oligomers. In the beta B2 subunit, the domains, each comprising two motifs, are separated by an extended linking peptide. A crystallographic 2-fold axis relates the two subunits of the dimer so that the N-terminal domain of one subunit of beta B2 and the C-terminal domain of the symmetry-related subunit are topologically equivalent to the two covalently connected domains of gamma B crystallin. The intersubunit domain interface is very similar to the intradomain interface of gamma B, although many sequence differences have resulted in an increase in polar interactions between domains in beta B2. Comparison of the structures of beta B2 and gamma B-crystallins shows that the two families differ largely in the conformation of their connecting peptides. A further extensive lattice contact indicates a tetramer with 222 symmetry. The ways in which insertions and extensions in the beta-crystallin effect oligomer interactions are described. The two kinds of crystallin are analysed for structural features that account for their different stabilities. These studies are a basis for understanding formation of higher aggregates in the lens. PMID- 1762147 TI - Hierarchy of globin complexes. The quaternary structure of the extracellular chlorocruorin of Eudistylia vancouverii. AB - The molecular dimensions of the extracellular, hexagonal bilayer chlorocruorin of the polychaete Eudistylia vancouverii, determined by scanning transmission electron microscopy (STEM) of negatively stained specimens, were diameter of 27.5 nm and height of 18.5 nm. STEM mass measurements of unstained, freeze-dried specimens provided a molecular mass (Mm) of 3480 +/- 225 kDa. The chlorocruorin had no carbohydrate and its iron content was 0.251 +/- 0.021 wt%, corresponding to a minimum Mm of 22.4 kDa. Mass spectra and nuclear magnetic resonance spectra of the prosthetic group confirmed it to be protoheme IX with a formyl group at position 3. SDS/polyacrylamide gel electrophoresis, reversed-phase chromatography and N-terminal sequencing suggested that the chlorocruorin consists of at least three chains of approximately 30 kDa and five chains of approximately 16 kDa; the two types of subunits occur in the ratio 0.26:0.74(+/- 0.08). Complete dissociation of the chlorocruorin at neutral pH in the presence of urea or guanidine hydrochloride, followed by gel filtration, produced elution profiles consisting of three peaks, B, C and D. Fractions B and C consisted of the approximately 16 kDa chains and fraction D consisted of the approximately 30 kDa subunits. Mass measurements of particles in STEM images of unstained, freeze dried fractions B and C provided Mm of 208 +/- 23 kDa and 65 +/- 12 kDa, respectively, in agreement with 191 +/- 13 kDa and 67 +/- 5 kDa obtained by gel filtration. Particles with Mm = 221 +/- 21 kDa were also observed in STEM images of unstained, freeze-dried chlorocruorin. These results imply that the chlorocruorin structure, in addition to the approximately 30 kDa linker subunits that have 0.26 to 0.47 heme groups/chain, comprises approximately 65 kDa tetramers and approximately 200 kDa dodecamers (trimers of tetramers) of globin chains. The stoichiometry of the tetramer and linker subunits calculated from molar amino acid compositions was 34 +/- 4 and 43 +/- 9. The complete dissociation of the chlorocruorin was accompanied by a 50 to 75% loss of the 55 +/- 14 Ca2+/mol protein, and was decreased to approximately 35% by the presence of 10 to 25 mM-Ca2+. Reassociation of dissociated chlorocruorin was maximal in the presence of 2.5 to 5 mM-Ca2+. The dodecamer and/or tetramer subunits in the absence or presence of Ca2+ exhibited very limited (less than 10%) reassociation into hexagonal bilayer structures, only in the presence of the linker subunit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762148 TI - Poly[d(A.T)] and other synthetic polydeoxynucleotides containing oligoadenosine tracts form nucleosomes easily. AB - Synthetic double-stranded polydeoxynucleotides of the general form poly[d(AnT).d(ATn)], with n ranging from 3 to 11, have been synthesized. The conformation of the polymers was investigated by circular dichroism spectroscopy and the polymers were examined for their ability to form nucleosomes. Although spectra show that a circular dichroism band characteristic of poly[d(A.T)] appears in the polymer family for n greater than 7, we demonstrate that even polynucleotides with the longest tracts of contiguous adenosine bases (n = 11) are able to form nucleosomes when reconstituted using a histone exchange procedure. Thus resistance to nucleosome formation does not coincide with the appearance of features similar to that of poly[d(A.T)] over the bulk of the nucleosomal DNA. Furthermore, we show that an approximately 150 base-pair poly[d(A.T)] itself, long thought to be refractory to nucleosome formation, can assemble into such a protein-DNA complex when reconstituted by a low-salt exchange procedure. Competitive assays show that the homopolymer reconstitutes about as well as heterogeneous sequences DNA. Our work, therefore, suggests that highly adenosine-rich sequences in vivo apparently have a function that operates at a level other than that of nucleosome structure. PMID- 1762149 TI - ms2i6A deficiency enhances proofreading in translation. AB - The hypermodified base 2-methylthio-N6-isopentenyladenosine (ms2i6A) at position 37 occurs frequently in tRNAs that read codons starting with uridine. Here we have studied how ms2i6A affects the accuracy of poly(U) translation in vitro. Deficiency leads to a higher rejection rate of tRNA4(Leu) by more aggressive proofreading on the wild-type ribosome, but with the initial selection step unchanged. Our data indicate that ms2i6A has no effect on codon-anticodon interactions on wild-type ribosomes as long as aminoacyl-tRNA is in ternary complex with EF-Tu and GTP. ms2i6A deficiency in the cognate poly(U) reader tRNA(Phe) leads to increased misreading when the near-cognate competitor tRNA4(Leu) is wild-type. ms2i6A deficiency in tRNA4(Leu) gives a decreased error level in competition with wild-type tRNA(Phe). PMID- 1762150 TI - Cysteine residue periodicity is a conserved structural feature of variable surface proteins from Paramecium tetraurelia. AB - The DNA sequences of the entire coding regions of the A and C type variable surface protein genes from Paramecium tetraurelia, stock 51 have been determined. The 8151 nucleotide open reading frame of the A gene contains several tandem repeats of 210 nucleotides within the central portion of the molecule as well as a periodic structure defined by cysteine residues. The 6699 nucleotide open reading frame of the C gene does not contain any identifiable tandem repeats or internal similarity but maintains a periodicity based on the cysteine residue spacing. The deduced amino acid sequences encoded by the two genes are most similar within the 600 amino-terminal and 600 carboxyl-terminal amino acid residues, the central portions show only limited sequence similarity. We conclude that internal repeats are not a conserved feature of variable surface proteins in Paramecium and discuss the possible importance of the regular pattern of cysteine residues. PMID- 1762151 TI - Evidence for horizontal gene transfer in Escherichia coli speciation. AB - After extracting more than 780 identified Escherichia coli genes from available data libraries, we investigated the codon usage of the corresponding coding sequences and extended the study of gene classes, thus obtained, to the nature and intensity of short nucleotide sequence selection, related to constraints operating at the nucleotide level. Using Factorial Correspondence Analysis we found that three classes ought to be included in order to match all data now available. The first two classes, as known, encompass genes expressed either continuously at a high level, or at a low level and/or rarely; the third class consists of genes corresponding to surface elements of the cell, genes coming from mobile elements as well as genes resulting in a high fidelity of DNA replication. This suggests that bacterial strains cultivated in the laboratory have been fixed by specific use of antimutator genes that are horizontally exchanged. PMID- 1762152 TI - Crystallization and preliminary X-ray analysis of the lactose-specific phosphocarrier protein IIAlac of the phosphoenolpyruvate: sugar phosphotransferase system from Staphylococcus aureus. AB - The IIA constituent of the lactose permease from Staphylococcus aureus has been crystallized in two different forms. Crystals of form I have been grown from polyethylene glycol 4000 with beta-octyl glucoside. They diffract to 3.0 A resolution and belong to space group C2 with unit cell dimensions a = 141.7 A, b = 130.7 A, c = 96.5 A and beta = 96.2 degrees. Form II crystals have been obtained from a solution containing polyethylene glycol 400, ammonium sulfate and manganese chloride. They diffract to at least 2.8 A resolution and belong to space group P2(1)2(1)2(1) with unit cell dimensions a = 89.9 A, b = 101.5 A and c = 90.9 A. PMID- 1762153 TI - Crystallization of diphtheria toxin. AB - Two new crystal forms (forms III and IV) have been grown of diphtheria toxin (DT), which kills susceptible cells by catalyzing the ADP-ribosylation of elongation factor 2, thereby stopping protein synthesis. Forms III and IV diffract to 2.3 A and 2.7 A resolution, respectively. Both forms belong to space group C2; the unit cell parameters for form III are a = 107.3 A, b = 91.7 A, c = 66.3 A and beta = 94.7 degrees and those for form IV are a = 108.3 A, b = 92.3 A, c = 66.1 A and beta = 90.4 degrees. Both forms have one protein chain per asymmetric unit with the dimeric molecule on a twofold axis of symmetry. Form IV is exceptional among all crystal forms of DT in that it can be grown reproducibly. Thus the form IV crystals should yield a crystallographic structure giving insight into the catalytic, receptor-binding and membrane-insertion properties of DT. PMID- 1762154 TI - Crystals of the complex between human growth hormone and the extracellular domain of its receptor. AB - Single crystals suitable for high-resolution diffraction studies have been grown of the human growth hormone (hGH) complexed to the extracellular domain of its cloned receptor from the human liver (hGHbp), using the technique of repeat seeding. The crystals are in space group P2(1)2(1)2, with a = 145.8 A, b = 68.6 A, c = 76.0 A, and diffract to at least 2.7 A resolution on a rotating anode X ray source. Analysis of the composition of these crystals showed the stoichiometry of the complex to be hGH: (hGHbp)2. This finding, coupled with biochemical data on the complex in solution, indicates that the biologically significant dimerization of the growth hormone receptor is mediated through a single hormone molecule. Structure determination of the complex is currently being completed. PMID- 1762155 TI - Crystallization of and preliminary X-ray data for the negative regulator (AmiC) of the amidase operon of Pseudomonas aeruginosa. AB - The negative regulator (AmiC) of the amidase operon of Pseudomonas aeruginosa has been purified from an over-expressing clone and crystalized. Crystals of diffraction quality were obtained from polyethylene glycol 4000 and ammonium sulphate. AmiC crystallizes in P4(2)2(1)2 (a = 104.4 A, c = 66.6 A) with one subunit in the asymmetric unit. Crystals diffract beyond 2.8 A. PMID- 1762156 TI - Crystallization and preliminary X-ray analysis of botulinum neurotoxin type A. AB - Botulinum neurotoxin serotype A was isolated from liquid culture of Clostridium botulinum. The pure Mr approximately 150,000 neurotoxin, composed of Mr approximately 50,000 light and Mr approximately 100,000 heavy chains, has been crystallized in three different crystal morphologies; all three have the same crystal form. The most suitable crystal form for X-ray analysis are bipyrimidal and crystallize in the hexagonal space group P3(1)21 (or P3(2)21) with one dimer per asymmetric unit. The unit cell dimensions are a = b = 170.5 A, c = 161.7 A. The crystals diffract to 3 A resolution. PMID- 1762157 TI - Analysis of the integration function of the streptomycete bacteriophage phi C31. AB - A 2.1 kb (1 kb = 10(3) base-pairs) segment of DNA from the streptomycete bacteriophage phi C31 was found to be sufficient to direct site-specific integration of plasmid vectors in Streptomyces ambofaciens and Streptomyces fradiae in the absence of any streptomycete origin of replication. Sequencing and analysis of phage, chromosomal and junction attachment sites of S. ambofaciens and S. fradiae revealed that recombination is conservative and that crossover takes place within three bases of homology between phage and host. Deletion analysis, sequencing and site-specific mutagenesis of the phi C31 DNA revealed a large open reading frame (ORF 613) whose expression was necessary for integration. This ORF begins near the point of crossover and reads away from the attachment site. A comparison of the predicted amino acid sequence of ORF 613 with known recombinases did not reveal any significant similarities. A genetic analysis of the amino-terminal region of ORF 613 suggested that translation could initiate at any one of three possible start codons. Primer extension experiments showed that transcriptional initiation occurred at a T and a C only four and five bases, respectively, from the site of crossover. This analysis suggested that ORF 613 would be separated from its promoter upon integration. PMID- 1762158 TI - Mutational specificity of the dnaE173 mutator associated with a defect in the catalytic subunit of DNA polymerase III of Escherichia coli. AB - We developed a system to examine forward mutations that occurred in the rpsL gene of Escherichia coli placed on a multicopy plasmid. Using this system we determined the mutational specificity for a dnaE173 mutator strain in which the editing function of DNA polymerase III is impeded. The frequency of rpsL- mutations increased 32,000-fold, due to the dnaE173 mutator, and 87 independent rpsL- mutations in the mutator strain were analyzed by DNA sequencing, together with 100 mutants recovered from dnaE+ strain, as the control. While half the number of mutations that occurred in the wild-type strain were caused by insertion elements, no such mutations were recovered from the mutator strain. A novel class of mutation, named "sequence substitution" was present in mutants raised in the dnaE173 strain; seven sequence substitutions induced in the mutator strain occurred at six sites, and all were located in quasipalindromic sequences, carrying the GTG or CAC sequence at one or both endpoints. While other types of mutation were found in both strains, single-base frameshifts were the most frequent events in the mutator strain. Thus, the mutator effect on this class of mutation was 175,000-fold. A total of 95% of the single-base frameshifts in the mutator strain were additions, most of which occurred at runs of A or C bases so as to increase the number of identical residues. Base substitutions, the frequency of which was enhanced 25,000-fold by the mutator effect, occurred primarily at several hotspots in the mutator strain, whereas those induced in the wild-type strain were more randomly distributed throughout the rpsL sequence. The dnaE173 mutator also increased the frequency of duplications 28,000-fold. Of the three duplications recovered from the mutator strain, one was a simple duplication, the region of which was flanked by direct repeats. The other duplications were complex, one half part of which was in the inverted orientation of a region containing two sets of inverted repeats. The same duplications were also recovered from the wild-type strain. The present data suggest that dnaE173 is a novel class of mutator that sharply induces sequence-directed mutagenesis, yielding high frequencies of single base frameshifts, duplications with inversions, sequence substitutions and base substitutions at hotspots. PMID- 1762159 TI - 1-aminocyclopropane-1-carboxylate synthase in tomato is encoded by a multigene family whose transcription is induced during fruit and floral senescence. AB - The key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene is 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (EC 4.1.1.14). It catalyzes the conversion of S-adenosylmethionine to ACC, the precursor of ethylene. We isolated complementary DNA sequences, ptACC2 and ptACC4, for two distinct and differentially regulated ACC synthase mRNAs expressed in ripe tomato fruit. The authenticity of the clones has been confirmed by expression experiments in E. coli. The predicted size of the encoded polypeptides (54,690 and 53,519 Da) is similar to that of the primary in vitro translation products and to the proteins found in vivo. The sequence of the gene encoding one mRNA, LE ACC2, has been determined and its transcription initiation site defined. Four additional genes, LE-ACC1A, LE-ACC1B, LE-ACC3 and LE-ACC4, have also been identified and the sequence of their coding regions determined. The LE-ACC1A and LE-ACC1B genes are adjacent to each other and are convergently transcribed. Their encoded polypeptides are 96% identical; the identity of the other polypeptides to each other varies between 50 and 70%. The proteins predicted to be encoded by the ACC synthase genes so far cloned from tomato and zucchini contain 11 of the 12 conserved amino acid residues found in various aminotransferases involved in the binding of the substrate and the cofactor pyridoxal-5'-phosphate. The data indicate that ACC synthase is encoded by a divergent multigene family in tomato that encodes proteins related to aminotransferases. PMID- 1762160 TI - Analysis of replicative intermediates produced during bacteriophage phi 29 DNA replication in vitro. AB - Replication of bacteriophage phi 29 DNA initiates at either end of its linear double-stranded DNA molecule and proceeds by a strand-displacement mechanism. In the present paper we have used an in vitro phi 29 DNA replication system to analyse by electron microscopy the replicative intermediates produced at different reaction times. Two types of replicative intermediates were observed: type I (full-length double-stranded phi 29 DNA molecules with one or more single stranded DNA branches) and type II (full-length phi 29 DNA molecules formed by a double-stranded DNA portion of variable length from one end plus a single stranded DNA portion spanning to the other end). Thus, the types of replicative intermediates produced in vivo were also formed in the in vitro phi 29 DNA replication system. Analysis of type I intermediates indicated that initiation of DNA replication occurs preferentially at both ends of the same DNA template, in a non-simultaneous manner. Type II intermediates appeared as early as two minutes after the reaction started, well before unit-length single-stranded phi 29 DNA molecules were synthesized. In addition, replication of recombinant phi 29 DNA templates lacking terminal protein at one end did not produce type II intermediates and led to an accumulation of full-length single-stranded phi 29 DNA molecules. These two observations strongly suggest that type II intermediates appear when two growing DNA chains, running from opposite ends, merge. PMID- 1762161 TI - An axial binding site in the Tetrahymena precursor RNA. AB - Previous studies allow the construction of three distinct models of the binding of G and arginine within the active site of the Tetrahymena self-splicing preribosomal precursor RNA. These models (base triple, axial I and axial II) are now distinguished by measurements on the specificity of RNAs with nucleotide substitutions at positions spanning the site. Because the semi-conserved unpaired nucleotide 263 has no effect on substrate or inhibitor selection by the Tetrahymena RNA we conclude that the axial I model is improbable. In contrast, data with substituted RNAs and nucleoside analogs suggest that nucleotide 265 makes a hydrogen bond with the substrate. Accordingly the active site appears axial because substrate contacts exist at more than one nucleotide on the 5' side of the P7 helix. The effects of this hydrogen bond are observable in cases where the donor or acceptor is on the RNA, whether nucleotide 265 is a purine or pyrimidine, or whether nucleotide 265 is mispaired, wobble paired or normally paired. This pattern is consistent with the axial II model. Molecular dynamics and energy minimization calculations lead to the same conclusions as these site directed substitutions; the base triple and axial I models are unstable dynamically. Under thermal agitation, the third model site (axial II) is transformed to a related, but more stable structure, axial III. The axial III active site is characterized by the extrusion of the conserved bulged base 263 from the P7 helix, a semi-pocket for G base formed by stacking of nucleotide 262, and formation of all bonds to the G base originally proposed for both the base triple and axial II sites. Because of these hydrogen bonds the axial III site is also consistent with data on enzymatic specificity. The axial III model indicates an unforeseen capacity for pocket formation within the groove of an RNA helix, suggests that the site may be unusually flexible, and bears on a hypothesis concerning the origin of the genetic code. PMID- 1762162 TI - [Clinical evaluation of cefdinir 10% granules in children]. AB - Cefdinir (CFDN, FK482) was evaluated in children with infections. CFDN was given at a daily dose of 6.4-19.8 mg/kg in 2 or 3 divided portions. CFDN was effective in 94% of 32 cases with respiratory tract, middle ear, urinary tract or skin structure infections. Side effects were loose stool and diarrhea (12.5%). In a pharmacokinetic study, 6.0 mg/kg of CFDN was given to each of the subjects before meal. Cmax was 0.81 +/- 0.38 microgram/ml, T 1/2 was 2.31 +/- 0.77 hours. Antibacterial activity against Staphylococcus aureus was the most excellent of oral cephem antibiotics tested. The data suggest that CFDN 10% granular preparation is safe and effective when used in children with infections caused by susceptible bacteria. PMID- 1762163 TI - [Clinical studies on 10% cefdinir granules in pediatric infections]. AB - Ten% cefdinir (CFDN, FK482) granular preparation, a new oral cephalosporin preparation intended for children, was given to children with various infections. The results obtained are summarized as follows. 1. Ten% CFDN granules were administered to a total of 21 children with upper or lower respiratory tract infections, urinary tract infections or infectious impetigo at daily doses of 6.4 18 mg/kg divided into 3 portions. Clinical efficacies were "excellent" in 13 patients, "good" in 7 patients and "unknown" in 1 patient (viral infection), hence an efficacy of 100% was obtained. 2. Bacteria identified in various disease cases included 19 strains of 7 species, and the eradication rate was 100%. 3. No side effects were noted in any of the children. Laboratory test results showed an abnormality in 1 case with eosinophilia. These results suggest that 10% CFDN granules as well as 5% CFDN granules may be a very useful and safe drug for the treatment of pediatric infections. PMID- 1762164 TI - [A clinical study on cefdinir 10% granule in pediatrics]. AB - Clinical evaluations of cefdinir (CFDN) 10% granule were carried out. The obtained results are summarized as follows. 1. Clinical responses to CFDN of 23 patients with pediatric infections were excellent in 11 and good in 8. The overall efficacy rate was 82.6%. 2. Bacteriologically, the eradication rate for 23 strains of bacteria identified to be pathogens was evaluated and was 82.6%. 3. Side effects observed were diarrhea in 2 of 25 patients. The incidence was 8.0%. Abnormal laboratory test results observed included 2 cases with elevation of GOT and 1 case with elevation of GPT. These results suggest that CFDN 10% granule, as well as 5% granule, may be a very useful and safe drug for the treatment of pediatric infections. PMID- 1762165 TI - [A clinical study on cefdinir in pediatric field]. AB - Cefdinir (CFDN) was administered to pediatric patients with acute infectious disease. A summary of the results obtained is as follows. 1. Pharmacokinetic parameters were determined in a girl. In comparison to reported data in adults, Tmax was shorter, Cmax was slightly lower, and the plasma half life of CFDN was somewhat longer. 2. Clinical efficacy was studied in 11 children with acute tonsillitis (6 patients), scarlet fever (1 patient), acute pharyngitis (1 patient), acute pneumonia (1 patient), acute otitis media (1 patient) and acute cervical lymphadenitis (1 patient). Responses to the treatment were excellent in 7 (63.6%) and good in 2 (18.2%). 3. No adverse reactions were noted in this study. PMID- 1762166 TI - [Clinical studies of cefdinir in pediatric infections]. AB - Five percent fine granule preparation of cefdinir (CFDN, FK482) was administered to 30 patients with acute febrile respiratory tract infections (RTI) at 4.9-21.1 mg/kg/day divided into 3 portions. And 10% fine granule preparation of CFDN was also administered to 11 patients with acute febrile RTI and 1 patient with urinary tract infection at 10.0-20.0 mg/kg/day divided into 3 portions. Good clinical effects observed in 21 of 24 patients (87.5%) with acute pharyngitis, 12 of 13 patients (92.3%) with acute tonsillitis, 2 of 4 patients (50.0%) with pneumonia and a patient with urinary tract infection. From these patients, 34 causative organisms were isolated. Ten (83.3%) of 12 strains of Staphylococcus aureus, all 6 strains of Streptococcus pyogenes and 1 strain of Streptococcus pneumoniae, 6 (46.2%) of 13 strains of Haemophillus influenzae and 1 strain of Escherichia coli were eradicated from these patients. Among the patients with pneumonia, CFDN 20 mg/kg/day dose group showed better clinical responses and better bacteriological effects against H. influenzae among the patients given CFDN 20 mg/kg/day dose group than those given CFDN 5 mg/kg/day dose group. Side effects were noted in 2 cases, one case had soft stools and the other had diarrheas. PMID- 1762167 TI - [Clinical evaluation of cefdinir 5% fine granules in pediatrics]. AB - Clinical evaluation in pediatrics on cefdinir (CFDN, FK482) (5% fine granules), a new oral cephem, was performed. 1. CFDN was administered to 112 pediatric patients with ages between 1 month to 13 years with various infections. Dose levels used were 3.0-8.9 mg/kg (mean 5.1 mg/kg) t.i.d. for 3-14 days (mean 6.7 days). The studied patients included 2 patients with scarlet fever, 6 with acute pharyngitis, 6 with acute rhinopharyngitis, 52 with acute purulent tonsillitis, 8 with acute bronchitis, 24 with acute pneumonia, 7 with acute urinary tract infections, 1 with acute vaginitis, and 6 with impetigo. Total doses ranged from 0.6 to 4.05 g. One hundred eleven of the 112 patients were evaluated for clinical efficacy and all the patients were evaluated for safety. 2. Clinical effects were excellent in 51 cases, good in 57, and fair in 3 with an extremely high efficacy rate of 97.3%. Efficacy rates were 100% in scarlet fever, acute pharyngitis, acute purulent tonsillitis, acute bronchitis, acute vaginitis and impetigo, and 83.3%, 95.7%, 85.7% in acute rhinopharyngitis, acute pneumonia, and acute urinary tract infections, respectively. Good clinical effects were observed regardless of diseases. 3. Causative organisms were identified in 79 cases, of which 71 were found to be monobacterial infections and 8 were found to be multi-bacterial infections. In mono-bacterial infections, clinical efficacies were 100% for those caused by Staphylococcus aureus/Streptococcus pyogenes/Streptococcus pneumoniae/beta-Streptococcus except those in A and B groups with an overall efficacy of 100% against Gram-positive cocci (GPC) and they were 89.5%, 100%, 100% for those caused by Haemophilus influenzae, Haemophilus parainfluenzae, and Escherichia coli, respectively, with an overall efficacy of 90.3% in Gram negative rods (GNR). In multi-bacterial infections also, a clinical efficacy of 100% was obtained. 4. Bacteriological effects were studied for 89 strains in the 79 cases. The eradication rate for a few strains of S. pneumoniae was low, 25%, but it was 100% for S. aureus, with the same results for S. pyogenes, and beta Streptococcus. The eradication rate on GPC was high 94.1%. Among GNR, 66.7% of E. coli, 50.0% of H. influenzae, and 71.4% of H. parainfluenzae was eradicated. The overall eradication rate for GNR was 55.3%, lower than that for GPC. Microbial substitutions were observed in 13 cases, with Haemophilus sp. replacing other bacteria. 5. Diarrhea and soft stools were noted in 4 and 2 patients, respectively. The severity of these side effects, however, was slight and it was possible to continue the CFDN treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762168 TI - [Pharmacokinetic, bacteriological and clinical evaluations of cefdinir 10% fine granules in pediatrics]. AB - Pharmacokinetic, bacteriological, and clinical studies on cefdinir (CFDN, FK482) (10% fine granules), a new oral cephem, were performed in pediatrics. 1. Bioequivalencies of plasma concentrations and urinary excretions of CFDN 5% and 10% fine granules were investigated on 3 pediatric patients with ages between 5 to 13 years administered with a drug in fasting state at a dose level of 3 mg/kg using a cross over method. Average plasma concentrations in a group of patients administered with 5% fine granules peaked at 3 hours after administration with a level of 1.05 +/- 0.29 micrograms/ml (mean +/- S.E.) and decreased to 0.12 +/- 0.05 micrograms/ml at 8 hours with a half-life of 1.48 +/- 0.09 hours. In the group administered with 10% fine granules, average plasma concentrations peaked at 2 hours after administration with a level of 1.32 +/- 0.12 micrograms/ml, and decreased to 0.20 +/- 0.11 microgram/ml at 8 hours with a half-life of 1.68 +/- 0.28 hours. The first 8-hour urinary recovery rates of CFDN in the 5% and 10% fine granules groups averaged 19.64 +/- 5.69% and 23.37 +/- 2.36%, respectively. Both average and individual plasma concentrations and urinary recovery rates in the patients of the 10% fine granules group were somewhat higher than those of the 5% fine granules group, but no significant differences were observed between the 2 groups including areas under concentrations. 2. CFDN 10% fine granule preparation was administered to 33 pediatric patients with ages between 1 to 13 years with various infections, and its clinical effects, bacteriological effects and safety were assessed. In 31 of the 33 patients (2 patients were excluded since they were with non-bacterial infections) clinical effects were excellent in all of 9 patients with scarlet fever (3), acute pharyngitis (3) or impetigo (3), excellent in 12 and good in 3 of 15 patients with acute purulent tonsillitis, and excellent in 4 and good in 3 of 7 patients with acute pneumonia. The overall efficacy rate was 100%. Bacteriological effects against causative organisms were evaluated. All the identified Staphylococcus aureus (4 strains) and Streptococcus agalactiae (1) were eradicated. Of 10 strains of Streptococcus pyogenes, 9 strains were eradicated and the other one was reduced. Of 7 strains of Haemophilus influenzae 4 were eradicated, 1 persisted and the fate of the remaining 2 were unknown. The overall eradication rate was 90.0%. Microbial substitutions were observed in 5 patients. The new, replacing bacteria were all Haemophilus spp.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762169 TI - [Laboratory and clinical studies on cefdinir (10% fine granules) in pediatric field]. AB - Clinical studies on 10% fine granules of cefdinir (CFDN), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows. 1. Half-lives of CFDN in plasma in 3 children when administered on an empty stomach were 1.77 hours (3 mg/kg per os) and 1.47 hours (6 mg/kg per os), respectively. Eight hour urinary excretion rates of CFDN were 21.5% (3 mg/kg per os) and 16.4% (6 mg/kg per os), respectively. 2. CFDN was administered to 11 children with various bacterial infections: 1 patient with scarlet fever, 1 with pharyngotonsillitis, 3 with acute bronchitis, 3 with pneumonia and 3 with urinary tract infections. The overall clinical efficacy rate was 90.9%. 3. Loose stool was noted in 1 patient. No abnormal laboratory test values were encountered. PMID- 1762170 TI - [Laboratory and clinical studies of cefdinir 5% and 10% fine granules in pediatric field]. AB - We have carried out laboratory and clinical studies on cefdinir (CFDN) 5% and 10% fine granule preparations. The results are summarized as follows. CFDN 5% fine granule preparation was given via oral route to each of 2 children in the fasting state at a single dose of 3 mg/kg. After administration, the mean peak plasma level of CFDN was 0.76 micrograms/ml at 4 hours and the mean half-life was 1.77 hours. The mean urinary excretion rate of CFDN was 31.5% in the first 12 hours after oral administration. CFDN 10% fine granule preparation and CFDN 100 mg capsule were given via oral route 3 children and to another child in the fasting state at single doses of 3 mg/kg and 2.63 mg/kg, respectively. After administration of 10% granules the mean peak plasma level of CFDN was 0.73 micrograms/ml at 2 hours and the mean half-life was 1.62 hours. The peak serum level obtained after administration of CFDN 100 mg capsule was 0.91 micrograms/ml at 2 hours and the half-life was 1.08 hours. The mean urinary excretion rate obtained with CFDN 10% fine granules was 26.2% in the first 8 hours after oral administration and the urinary excretion rate obtained with CFDN 100 mg capsule was 19.7% in the first 12 hours after oral administration. Treatment with CFDN 5% fine granules was made for a total of 48 cases of pediatric bacterial infections including 21 cases of tonsillitis, 12 cases of scarlet fever, 3 cases of pharyngitis, 5 cases of impetigo, 1 case of subcutaneous abscess, 1 case of furuncle, 5 cases of UTI. Results obtained were excellent in 30 cases, good in 18 cases. Treatment with CFDN 10% fine granules was made for a total of 16 cases of pediatric bacterial infections including 6 cases of tonsillitis, 3 cases of pneumonia, 4 cases of scarlet fever, 2 cases of impetigo, 1 case of UTI. Results obtained were excellent in 8 cases, good in 7 cases, poor in 1 case. No significant side effects due to the drugs were observed except 2 cases (1 case with 5% preparation and another with 10%) with eosinophilia, 3 cases (all with 5%) with diarrhea and 1 case each of elevated GOT & GPT (with 5%) and elevated GOT, GPT & Al-P (with 10%). PMID- 1762171 TI - [Pharmacokinetic, bacteriological and clinical studies on cefdinir fine granules in the field of pediatrics]. AB - The Pharmacokinetics and clinical effectiveness of cefdinir (CFDN, FK482) were examined in pediatric patients. The results are summarized as follows. 1. Plasma concentrations and urinary excretions of CFDN after administration of 5% fine granules were investigated on 4 children at a dose level of 6 mg/kg. Average plasma concentrations peaked at 4 hours after administration at 0.99 micrograms/ml with a half-life of 2.12 hours. The first 24-hour urinary recovery rates of CFDN in 3 children averaged 22.0%. 2. CFDN was given to 24 children (11 with pharyngitis, 3 with tonsillitis, 8 with scarlet fever, 1 with urinary tract infection and 1 with enteritis due to Salmonella); 15 were treated with 5% fine granules and 9 with 10% fine granules at daily doses of about 10 mg/kg in 2 to 3 divided portions. Clinical effects were excellent in 16, good in 7 and not evaluable in 1, with an overall efficacy rate of 100%. 3. Identified causative organisms were 12 strains of Streptococcus pyogenes, 4 of Haemophilus influenzae, 5 of Haemophilus parainfluenzae, 1 of Escherichia coli, and 1 of Salmonella. Bacteriological effects were rated as "eradicated" for 19 strains, "unchanged" for 4 with an eradication rate of 82.6%. 4. No side effects were observed. As for abnormal laboratory test results, a transient decrease of white blood cells was observed in 1 patient. 5. The CFDN fine granule preparations were preferably accepted by the children. 6. The fine granular preparations of CFDN, a new oral antibiotic, were useful for the treatment of bacterial infections in pediatrics. PMID- 1762172 TI - [Pharmacokinetic and clinical studies of cefdinir in the pediatric field. Pediatric Study Group of Cefdinir]. AB - We studied pharmacokinetics and clinical effects of 5% and 10% fine granules of cefdinir (FK 482, CFDN), a new oral cephalosporin, in the pediatric field and the following results were obtained. 1. Pharmacokinetics (blood concentration and urinary excretion) Pharmacokinetics of CFDN in 163 children was investigated. Cmax and T 1/2 were 0.92 +/- 0.45 micrograms/ml and 1.95 +/- 1.06 hours, respectively, in the fasting state, and were 0.63 +/- 0.29 micrograms/ml and 2.26 +/- 0.65 hours, respectively, in the non-fasting state, at a dose level of 3 mg (potency)/kg. At a dose level of 6 mg (potency)/kg, Cmax and T 1/2 were 1.29 +/- 0.49 micrograms/ml and 2.11 +/- 1.85 hours, respectively, in the fasting state and were 1.28 +/- 0.48 micrograms/ml and 2.01 +/- 0.84 hours, respectively, in the non-fasting state. Data of Cmax and AUC showed that blood concentration of the drug depended on dose levels. Urinary recovery rates in the first 8 hours were 20.5 +/- 8.8% in the fasting state and 14.8 +/- 5.9% in the non-fasting at a dose level of 3 mg (potency)/kg and 16.5 +/- 6.7% and 17.8 +/- 2.4%, respectively, at 6 mg (potency)/kg. 2. Clinical effects Clinical effects of CFDN on various infections were studied in 612 children who were treated with 5% fine granules of CFDN (5% granule group) and in 208 with 10% fine granules of CFDN (10% granule group). CFDN granules were administered mainly at daily doses of 9.0 18.0 mg (potency)/kg in 3 divided portions. Clinical efficacy rates in 428 children of the 5% granule group and in 159 of the 10% granule group from whom causative bacteria were isolated, were 94.9% and 96.2%, respectively. The clinical efficacy rates for patients who were responsive to previous antibiotic therapy were 91.2% in the 5% granule group and 100% in the 10% granule group. Bacteriological eradication rate was 82.1% for 491 strains in the 5% granule group, and was 84.0% for 175 strains in the 10% granule group. The incidences of side effects were 3.9% (24/608) in the 5% fine granule group and 5.8% (12/206) in the 10% granule group. All of the side effects were slight gastrointestinal disorders, and no serious side effects were found. As for clinical laboratory test results, slight elevations of eosinophile, platelet or transaminase were observed. Based on the above results, it is considered that the appropriate dose levels of CFDN for pediatric infections ranged from 9.0 to 18.0 mg (potency)/kg a day, divided into 3 portions. PMID- 1762173 TI - [Biological and pharmacological properties of Clostridium perfringens alpha toxin]. PMID- 1762174 TI - [Antibacterial and bactericidal activities of tea extracts and catechins against methicillin resistant Staphylococcus aureus]. AB - We examined tea extract, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antibacterial and bactericidal activities against methicillin resistant Staphylococcus aureus (MRSA) and food poisoning strains of S. aureus. Twenty percent tea extract (50 microliters), EGCg (63 micrograms) and TF3 (125 micrograms) added to one ml of culture medium each inhibited the growth of all strains of MRSA and food poisoning S. aureus tested. Tea extract showed also a bactericidal activity against MRSA even at the same concentration of as in ordinarily brewed tea. EGCg at a concentration of 250 micrograms/ml showed a bactericidal activity against MRSA but not against food poisoning S. aureus, but at 500 micrograms/ml reduced markedly the viable number within 48h. These results suggest that tea and catechin can be used as prophylactic agents against MRSA infection. PMID- 1762175 TI - [Cross reactive antigens of Acholeplasma laidlawii and L-form of Staphylococcus aureus]. AB - We demonstrated that the membrane of Acholeplasma laidlawii PG8 and L-form of Staphylococcus aureus, both of which induce cellular immunity in BALB/c mice, were antigenically related each other. Foodpad responses of the mice immunized with a mixture of either antigen and Freund's complete adjuvant showed clearly a cross reaction when challenged with the other antigen. Cross responses to incorporate 3H-thymidine to the spleen lymphocytes of the mice immunized with either antigen occurred in the presence of the other antigen. Furthermore, the purified T cells, but not B cells, of the spleen were activated in the presence of antigen-presenting cells. These antigens existing in the membrane fractions of both microorganisms were purified by Razin's method. Finally, these membrane components of A. laidlawii and L-form of S. aureus were subjected to gel electrophoresis and transferring to nitrocellulose membrane and used to stimulate the spleen lymphocytes of the mice immunized with A. laidlawii or of non immunized mice. The fractions representing molecular weights of approximately 45 kD, 25 kD, and 13 kD of both microorganisms consistently stimulated the lymphocytes of the immunized mice but not those of non-immunized mice. PMID- 1762176 TI - [Clinical diagnosis and laboratory data]. AB - Modern medicine can not be practiced without laboratory tests. Laboratory tests play a vital role from the initial stage of clinical examination. The Japanese Society of Clinical Pathology has formed a committee specifically dealing with the effective and economic use of lab tests without missing or duplicating the important tests. As is shown in table 1 in the main text "Essential Laboratory Tests" were initially agreed as those tests a patient should take when visiting a clinic regardless of the complaint. From an early stage, laboratory tests were done simultaneously with history-taking and physical examinations. Then the "Initial Impression" is obtained and "Organ-oriented 1st and 2nd screening tests" and confirmatory tests will be done to make the final diagnosis. To evaluate the validity of the "Essential Laboratory Tests", we performed the tests on 1026 patients who visited our general medicine clinic for the first time. We compared the Initial Impression with or without Essential Laboratory Tests. Cases in which a diagnosis could not be made by history-taking and physical examination were decreased from 17.4% to 8.0% by performing the essential laboratory tests. Diagnoses made without the essential laboratory tests were found to be mistaken in 10.4% and the additional use of the tests was suggested to lead to a more accurate diagnosis. In 110 cases, diseases unrelated to the chief complaints, were discovered. Even for the respiratory tract infection, CRP and WBC count, which were included in the essential laboratory tests, were very informative. PMID- 1762177 TI - [Systematization of clinical laboratory--some problems caused from specimen transport through laboratory reports]. AB - Through error and trials we have designed an ideal system for the clinical laboratory. Truly, it has been a very difficult task requiring our long-term experience working in the clinical laboratory. For example, if we purchase new examination equipment without any consideration or if we decide what type of equipment to introduce according to the common advice of the purchase committee of the hospital or the medical school, then we cannot design an ideal system of laboratory examinations and are forced to invest a large sum of money in vain. Moreover, the use of innumerable examination containers or test tubes which are disposable, can become a financial burden to the hospital. We have been trying to design a system of laboratory automation for more than ten years and have been successful in designing not only a specimen transport system using conveyer-belts but also various kinds of examination robotic systems. This report describes our own examples of designing a system of laboratory automation. PMID- 1762178 TI - [Computer-assisted laboratory diagnosis--principles and clinical application]. AB - Methods of computer-assisted diagnosis based on laboratory data are divided into so called rule-base system in which the diagnostic knowledge of physicians is programmed and those using multivariate analysis and mathematical models such as fuzzy interference. In this report, the principles and the technique of matrix discrimination method, which belongs to the latter group, are described, and its usefulness in clinical diagnosis evaluated. By the present method, subjects (diseases) are separated from two or more groups of subjects (diseases) to be discriminated on the basis of laboratory data. The method, based on the linear discrimination analysis, is characterized by optimization of selection of subjects to be discriminated and selection of test items and inference by the use of a discrimination curve. When this method was applied to discrimination of healthy individuals and patients with various liver and biliary disorders (11 diseases), all healthy individuals were discriminated from the patients. A mean of 97.0% of patients with hepatic parenchymal disorders were found in the top two, and 86.2% of those with space-occupying diseases in the top three, of the 12 diseases from which the disease of each patient was to be estimated. This diagnostic ability of the matrix discrimination method far exceeded the physicians' expectations. PMID- 1762179 TI - [Laboratory interpretive reporting system. A prototypical approach for knowledge representation in acid-base and electrolyte disorders]. AB - It is important to realize the problem-oriented diagnosis and the goal-oriented one to support general physicians as clinical decision makers under so many laboratory tests more than full with using practically. A prototypical model for computer-assisted interpretation of laboratory data was presented. To achieve both function of the problem-oriented inference and the goal-oriented one, knowledge base in this system was structured using the methods of semantic network and qualitative reasoning. Superficial knowledge level characterized by the intuitive reasoning from test results to diseases and deep knowledge level referring to the relations among the pathophysiologic states were stratified, and the heuristics based on the experiences at bed-side were incorporated in this knowledge representation. The pathophysiologic states were distilled from the textbooks and the articles, and were linked together by the relationships of cause and result, such as functional, constraint or conceptual relationship. Diagnostic knowledge on the computer was reconstructed by the causal network representing the pathological process as qualitative chaining between the pathophysiologic states, and was corrected and compiled by the clinical experiences and the experimental facts. Abnormal test data became a trigger of the start of inference, and presumptive pathophysiologic states and diagnoses were fired on the causal network. Consequently, the most important pathophysiologic states might become to be clear to understand the cause of changes of laboratory data. PMID- 1762180 TI - [Revolution of paradigm in clinical diagnosis--from the mechanization to the intelligent being]. AB - The medical advancements, during the 20th century symbolize the industrialization of medical technologies, i.e., many clinical tests are carried out by the highly advanced automated machines. Also, the concept of intelligent processing of clinical diagnosis seems to have been established in the practice. However, it may be an illusion caused from the term artificial intelligence (AI) which attracts the attention of not only specialists of computer science but also clinicians. The essential nature of AI, especially of expert consultation systems is the same as the existing theories, such as Bayes' theorem, Boolean algebra, multivariate statistical analysis, and Fussy theorem, i.e., the evaluation of a weighted sum of multiple parameters. The weak point of these theories is the lack of time parameter. Therefore, the models using a time parameter including physiological simulation, dynamics model, Weibull model and Markov process are important to realize the revolution of clinical diagnosis from the standpoint of intelligent science and technology. PMID- 1762181 TI - [DNA diagnosis in endocrinological disease--pituitary disease]. AB - Endocrine disorders have long been diagnosed by symptoms, before hormones were able to be measured by immunoassays. Recently, as molecular biological methods developed, DNA diagnosis has become available in many diseases including endocrine disorders. We present here DNA diagnosis in connection with anterior pituitary hormones. Our studies on thyrotropin (TSH) producing pituitary adenomas showed that TSH beta-subunit mRNAs of the adenomas were the same as those from normal pituitary tissues. Congenital isolated TSH deficiency is rare disease causing hypothyroidism including cretinism, severe mental and growth retardation. We have studied 3 families with consanguineous marriage and 2 families which were descendants of closed colonies. The molecular pathogenesis were elucidated in the cases of 3 Japanese families with consanguineous marriage. They had a same missense mutation in the 2nd exon of the TSH beta-subunit gene which made a restriction enzyme site, and could be analyzed either by genomic Southern blot analyses or by restriction enzyme digestion after amplification of genomic DNA by PCR. Congenital deficiency of growth hormone, prolactin, and TSH was first described in Snell dwarf mice. The gene encoding the nuclear factor Pit-1/GHF-1, which transactivates promoters of both growth hormone gene and prolactin gene, was shown to be the cause of Snell dwarf mice. A similar human case arose from a family with consanguineous marriage, and the relation with the pit-1/GHF-1 gene is now under study. PMID- 1762182 TI - [Molecular diagnosis of leukemia and lymphoma]. AB - Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes. PMID- 1762183 TI - [DNA typing of HLA]. AB - Recent advance of molecular biology and genetic engineering has made a profound influence on clinical and laboratory medicine. In this article we will review present aspects of DNA typing of HLA-class II alleles. The HLA system is characterized by its highly genetic polymorphisms. HLA -class I (A, B, C) molecule consists of alpha 1, alpha 2, alpha 3, and beta 2-microglobulin domain, and HLA-class II (DR, DQ, DP) molecule consists of alpha 1, alpha 2, beta 1, and beta 2 domain. Differences of amino acid sequences determining polymorphisms of HLA-class II molecule are located mainly on the beta 1 domain, while alpha 1 chain of DQ molecule is also polymorphic. Polymerase chain reaction (PCR) has enabled us to make great progress in DNA typing of HLA, in place of RFLP (restriction fragment length polymorphisms) analysis. One of the most important and valuable advantages is to make us non-radioisotopic detection method available. There are several methods for the further analysis of products of PCR amplification; 1) dot-blot hybridization, 2) PCR-RFLP, 3) PCR-SSCP (single strand conformation polymorphism), 4) DGGE (denaturing gradient gel electrophoresis), 5) direct sequencing. As for dot-blot hybridization, there are also several methods for detecting hybridization; 1) radioactive detection with 32P - labelled probes, 2) colorimetric reaction and 3) chemiluminescent assay. Newly developed chemiluminescent assay yields as high sensitivity just as radioactive probes. HLA D and -DP specificities have been typed cytologically by mixed lymphocyte culture (MLC) or primed lymphocyte test (PLT) method. Cytological typing will be replaced by PCR analysis in near future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762184 TI - [Theophylline pharmacokinetics in patients with liver diseases with reference to estimated hepatic blood flow]. AB - Pharmacokinetics of theophylline were determined in patients with liver cirrhosis and idiopathic portal hypertension with reference to estimated hepatic blood flow assessed by indocyanine green (ICG). Decreased plasma clearance of theophylline was noted in patients with liver cirrhosis and the clearance was significantly lower in Child C group than in Child A, B groups (17.5 +/- 3.4 ml/Kg/hr vs 27.6 +/- 8.7, p less than 0.05). Theophylline has been classified as a drug with a low hepatic extraction ratio and it has been believed that changes in hepatic blood flow have little effect on its clearance. The results of present study indicate that theophylline clearance is basically not related to ICG clearance but to theophylline extraction ratio, supporting the common belief. However, it is noteworthy that the clearance was related to decreased hepatic blood flow rather than extraction ratio in a cirrhotic patient with huge extrahepatic shunt, suggesting that hepatic clearance of this drug could be affected by hepatic blood flow under some circumstances. PMID- 1762185 TI - [Detection of immune complex by C1q solid phase enzyme immunoassay]. AB - We have developed a new and improved method for detecting immune complexes (IC) by C1q solid-phase enzyme immunoassay (CSP-EIA). The sensitivity of this method was between 0.62 micrograms/ml and 1.25 micrograms/ml, and values in normal individuals were 1.8 micrograms/ml and less. The positive rate of IC of sera in which abnormal values were detected by autoimmune disease associated laboratory examinations was 50.0% in RA (2+), 20.4% in ANA (+), 60.0% in CH50 (less than 10), 41.7% in LE latex (+). In sera of RA (2+), the higher the value of CRP detected by a semi-quantitative analysis was, the higher the frequency having abnormal high IC values was. The number of IC positive sera, in which enzyme linked immunoglobulins were detected, was 18 of 68 (positive rate 26.5%). The number of IC positive samples in asymptomatic carriers of sera, whose titer of anti-HTLV-I antibody was positive by gelatin particle agglutination assay (PA), was 14 of 67 (pos. rate 18.4%). All of these 14 samples were high positivity of anti-HTLV-I antibody (titer greater than or equal to 256 times). In urine of some patients with urogenital diseases, IC-like substances to show positive reaction by our CSP-EIA were detected. However, any positive reaction was not detected either by an anti-C1q- or an anti-C3d method. Studies are in progress to elucidate detailed characterization of the IC-like substances. PMID- 1762186 TI - [Difference of blood cell counts with reference blood cell counters in three different makers]. AB - To determine the difference of CBC values in different blood cell counters, we have measured the values of CBC by using reference cell counters of three major makers; Coulter, Sysmex and Technicon. Thirty ml of whole blood was taken from 2 healthy individuals and mixed with 45 mg of EDTA -2K. The blood samples were then sent to reference laboratory of each maker under identical conditions. The determination of cell counts was performed 4 hours after taking blood. Ten consecutive analysis were then carried out and the mean of 10 values was calculated. The apparent difference was displayed in leucocyte and platelet counts. In both of two samples, the highest values of either leucocyte or platelet count was obtained with Coulter instrument. And second high values were noted with Sysmex counter and the lowest values were observed by Technicon instrument. The extent of difference between each instrument was over 10% in case of platelet count and was 5 to 10% in leucocyte count. The difference of erythrocyte count, Hgb level, hematocrit value and MCV also existed, but the extent of difference was within 5% in all of these examinations. Since CV of each examination was sufficiently low level, this difference might be due to the difference in accuracy of reference cell counter of each maker. These results suggest that distinct differences of CBC count, particularly platelet and leucocyte count can be produced by the different procedures of calibration for reference counter in each maker of automated blood cell counter. PMID- 1762187 TI - [Analysis of CK-MB using immunoinhibition method]. AB - The significance of creatine kinase (CK) in the diagnosis of acute myocardial infarction was evaluated. The serum level of CK-MB, a CK isozyme was determined by the immunoinhibition method. The CK-MB activity could be determined by the immunoinhibition method in a short time with an autoanalyzer, suggesting that the immunoinhibition technique is adequate as a method of emergency examination. The immunoinhibition method has the disadvantage of error induction because of contamination with CK-BB, CKm and macro-CK by this method. Thus, CK-MB activity should be determined in parallel with total CK activity. When a significant contribution from CK-BB is suspected, its presence should be confirmed by other methods. The present results suggest that the efficiency of coronary artery reperfusion therapy can be evaluated earlier by determination of CK-MB activity than by that of total CK activity. PMID- 1762188 TI - [Usefulness of CK-MM isoforms for early stage of acute myocardial infarction using electrophoretic technique]. AB - MM isoform of CK (EC 2.7.3.2) was able to detect by high voltage electrophoresis. Sequential blood samples were collected from the patients with acute myocardial infarction and MM isoform (as MM3/MM1 ratio), CK activity and CK-MB activity were tested. Time of the maximum MM3/MM1 ratio from the onset was 9.4 hrs (average of 16 cases) whereas 15.9 hrs on CK-MB activity and 17.3 hrs on CK activity were detected. In vitro time course of CK-MM isoform from myocardial and skeletal muscle extracts was tested. MM3 band was gradually converted into MM2 and then MM1 band, but MM3 isoform from myocardium was changed less than skeletal muscle. From these results, it is suggested that abnormal MM3/MM1 ratio on myocardial infarction continues relatively longer time than that on skeletal muscle disease. PMID- 1762189 TI - [Immunoinhibitory determination of CK-MM subbands by monoclonal antibody]. AB - The measurement of CK-MM isoform by monoclonal antibody and its clinical application were summarized. The tissue type of CK-MM3 isoform was completely inhibited, MM2 isoform was about 57% and the serum type of CK-MM1 isoform was not inhibited by use of monoclonal antibody. This method enabled selective immunoinhibitory measurement of tissue type of CK-MM isoform. The heat lability and inhibition by EDTA suggested that it is a metal-depending enzyme. The analysis of MM isoform offers a promising alternate, non-invasive method to detect and follow up AMI and successful reperfusion. The MM3/MM1 ratio has been found to peak at about 2 to 6 hours, making it a quicker responding parameter to AMI than MM3 alone and significantly more responsive than the total CK or CK-MB. An MM3/MM1 ratio greater than 1.0 appears to be a practical cutoff point for detection of the pathological release of MM3 from tissue. Reperfusion therapy should be instituted within about 2 to 4 hours of AMI onset. PMID- 1762190 TI - [The determination of CK-MB protein mass]. AB - It has been well known that the determination of CK-MB is a useful parameter for the diagnosis of acute myocardial infarction (AMI). Currently, several methods such as Electrophoresis, Ion-exchange chromatography, Immunoinhibition method and Protein mass determination are available. From a point of the diagnosis of AMI, the method should be satisfied with the requirements of high speed, ease to perform, high analytical specificity and high analytical sensitivity. However, there are no appropriate methods which can satisfy all of the requirement. In this paper, we have introduced the present situation concerning the determination of CK-MB in our hospital and discussed the results of study on the IMx method based on the determination of protein mass of CK-MB. We obtained good results in the fundamental study and found some advantages of protein mass determination. The first advantage was its high analytical specificity by use of monoclonal antibody. The second advantage was its high analytical sensitivity because of its low detection limit. The third advantage was the stability of sample because the antigenicity of CK-MB to the antibody of reagent is stable comparing with that of enzyme activity. From those advantages, the mass determination of CK-MB will be a useful method for the diagnosis of AMI in the near future. PMID- 1762191 TI - [Early diagnosis and early detection of successful reperfusion by latex agglutination turbidimetry of serum myoglobin in patients with acute myocardial infarction]. AB - As latex agglutination turbidimetry of serum myoglobin (Mb) levels is simple, rapid and high sensitive method, it can be applied for early diagnosis and reperfusion therapy (PTCA, PTCR) in patients with acute myocardial infarction (AMI). The measurement of serum Mb levels is useful for early diagnosis of AMI, and we conclude that the measurement of serum Mb levels is useful and suitable for rapid judging on success or failure of reperfusion therapy use of the disappearance rate of it. PMID- 1762192 TI - [Biochemical diagnosis for acute myocardial infarction; myosin light chain]. AB - Immunoassays for cardiac myosin light chains (LC) are important biochemical tests for diagnosis of acute myocardial infarction (AMI). LC appears in the serum 4-12 hours after AMI. The most unique characteristic of the time-course of LC is that the elevation of LC in the serum lasts for 1-2 weeks, which allows the retrospective diagnosis of AMI when cardiac enzymes in the serum are decreased to the normal level. This long time-course is due to the continuous liberation of LC from the infarcted myocardium, which could be confirmed by the cardiac scintigram using anti-myosin heavy chain antibody. The serum LC level is also useful in predicting the extent of the cardiac wall damage since the peak LC level reflected well the ventricular ejection fraction or the presence of mechanical complications, such as the formation of ventricular aneurysm. Immunoassays for cardiac LC have recently been improved by the introduction of ELISA using two monoclonal anti-light chain antibodies. ELISA can be finished within 3 hours, which will help to make cardiac LC measurement one of the most important biochemical tests for diagnosis of acute myocardial infarction. PMID- 1762193 TI - [Evaluation of [troponin-T] as a new biochemical marker for acute myocardial infarction]. AB - Troponin (Tn) and tropomyosin (Tm) are located in the thin actin-containing filaments. Tn, a complex of three subunits (Tn-C, Tn-I and Tn-T), plays an important role in muscle contraction via calcium metabolism. In the present study, we evaluated the usefulness of a serum Tn-T assay in patients with acute myocardial infarction. The method, based on the sandwich immunoassay, was developed for the determination of serum Tn-T. The analytical precision data were good enough for routine analysis (CVs of repeatability and day-to-day reproducibility were between 3.2 to 6.2%). The values obtained on 60 healthy adults were below 0.2 ng/ml. Physical activity (mountain climbing and golf) increased serum total CK and myoglobin, but did not increase Tn-T. In myocardial infarction, serum Tn-T was up to 20 times higher than the cut off value at admission, and had a large peak at around 14 hr and another small peak at 40 to 55 hr after the onset. The ratio of Tn-T at around 14 and 32 hr (14/32) was an excellent marker for successful reperfusion. All cases of successful PTCA, had a ratio higher than 1.0. PMID- 1762194 TI - [Magnetoencephalographic studies on spike foci using a 37-channel biomagnetometer system]. AB - We report the results of a clinical trial of Magnetoencephalography (MEG) on spike foci in patients with epilepsy, which was performed from December 1990 to June 1991 at The University of Tokyo Hospital. Fifty patients with focal epilepsy; 26 primary epilepsy, 24 secondary epilepsy (7 brain tumor, 4 arteriovenous malformation, 4 encephalitis, 3 porencephaly, 2 arachnoid cyst, 1 brain abscess, 1 hemimegaloencephaly, 1 Lance-Adams syndrome, 1 hygroma), and ten normal subjects were enrolled in this study. MEG data were recorded using a 37 channel biomagnetometer system SMI-1001 (BTi Magnes, Biomagnetic Technologies, Inc., San Diego). A simultaneous 19-channel EEG recording with linked-ear reference was also obtained. The overall study was completed safely and none of the normal subjects showed abnormal paroxysmal MEG activity. Two patients showed interictal EEG spikes which would not have been noticed without first noting the presence of corresponding prominent MEG spikes. On the whole, the MEG signal seemed to have a wider frequency bandwidth than EEG. In most cases, the source localization predicted by MEG corresponded well with the EEG findings. The relative accuracy of MEG spike source localization was estimated to be within a cubic centimeter from the cases which showed tightly clustered localization of individual spikes. High-pass filtering reduced interference by superimposed slow wave activity, thereby improving the localization of spike sources. These results demonstrate that 37-channel biomagnetometer system could be a useful tool for analyzing epileptic spike sources. PMID- 1762195 TI - [A new method for immunological detection of fecal blood, using colloidal gold labeled with anti-human hemoglobin monoclonal antibody]. AB - Application of colloidal gold agglutination to detection of fecal blood was done. Colloidal gold labeled with monoclonal antibody recognized human hemoglobin was agglutinated with hemoglobin and changed the color from red to gray. The color that diminished rapidly with an antigen was unchangeable from 30 min to 4 hr. Reaction was single step, and positive tests were easily distinguished from negative tests. Detectable hemoglobin concentration was 0.5 micrograms/ml. Comparison of colloidal gold agglutination with other methods, as low as latex agglutination and RPHA, showed good agreements in 1409 fecal samples. Colloidal gold agglutination method is superior in easiness of judgement and unnecessity of keeping time, and will be suitable for mass screening for colorectal cancer using 96 well microplate. PMID- 1762196 TI - [Serum lipid and apolipoprotein levels in patients with chronic pancreatitis]. AB - Serum lipid and apolipoprotein (apo A-I, A-II, A-IV, B, C-II, C-III, E and H) levels were determined in 26 patients with chronic pancreatitis without complications such as liver disease or diabetes mellitus. These patients were divided into two groups, CP-I (n = 16) and CP-II (n = 10), according to the clinical criteria for chronic pancreatitis. HDL-cholesterol and apo A-I levels in CP-I and CP-II groups significantly decreased compared to those in sex- and age matched healthy controls (p less than 0.05), whereas there were not significant differences in triglyceride and total cholesterol levels between these groups and controls. On the other hand, apo A-IV levels in CP-I and CP-II were 7.1 +/- 1.0 mg/dl and 8.3 +/- 1.5 mg/dl, respectively and these values were significantly lower than 11.2 +/- 1.8 mg/dl in controls (p less than 0.001). In this study, the serum lipids apparently showed normal levels in patients with chronic pancreatitis who had no severe complication, and the markedly low apo A-IV levels in these patients were considered to be mainly due to the decrease of lipid absorption from the intestine. PMID- 1762197 TI - [Converse changes in serum levels of immunoglobulins (IgG, A and M) and complement components (C3, 4) during pregnancy]. AB - Sequential changes in serum levels of the immunoglobulins IgG, A and M and of the complements C3 and C4 during pregnancy and the postpartum period were studied in 8 healthy women. Serum IgG and A levels decreased gradually during pregnancy, but increased significantly during the first three months following delivery. Serum IgM level also decreased during pregnancy, reaching its minimum during the second trimester, but increased thereafter. In contrast, C3 and C4 levels increased significantly during pregnancy and reached their maximum levels during the last trimester. After delivery, levels of these two components decreased gradually for the next six months. The complement system may operate as a compensatory autoregulatory mechanism in the suppression of the humoral immune system during pregnancy. PMID- 1762198 TI - [Evaluation of serum myoglobin level in patients with muscular disorder and renal failure]. AB - Since myoglobin is a low molecular weight proteins and most serum myoglobin is usually excreted into the urine, but serum myoglobin is elevated in patients with renal failure. This elevation hampers diagnosis of muscular damage in patients with renal failure. We studied the influence of renal function on serum myoglobin level and estimated corrected myoglobin levels. We first examined the correlation of serum myoglobin level with levels of serum creatinine and serum beta 2 microglobulin in patients without muscular damage. Creatinine level was more highly correlated with serum myoglobin level than with beta 2 microglobulin level. Measured myoglobin level was corrected using the regression line obtained from the correlation between levels of myoglobin and creatinine, and the corrected myoglobin levels thus obtained were within a reasonable range. The influence of renal failure was compensated for by this correction. We then measured myoglobin level and creatine kinase activity in patients with various heart muscle or skeletal muscle diseases, with or without renal failure, and compared measured myoglobin levels with the corrected ones. In these patients, myoglobin level changed faster than such muscle enzymes as creatine kinase. Thereafter, we found that the stage and degree of muscular damage could be estimated from both corrected myoglobin level and creatine kinase activity, even in patients with renal failure. In conclusion, corrected serum myoglobin level might be a useful diagnostic marker of muscle damage even in patients with renal failure. PMID- 1762199 TI - [Effect of plasma on analysis of lymphocyte subsets]. AB - We examined the effect of plasma on the analysis of lymphocyte subsets with a flow cytometer using whole blood cells. Removal of plasma from whole blood by washing them before labelling the lymphocytes with fluorescein-conjugated antibodies reduced the proportion of CD5+CD19+ cells and increased the proportions of CD16+ CD57- and CD16+ CD57+ cells, as compared with those measured without washing, but did not change the proportions of CD5+ CD19-, CD5- CD19+, CD4+ CD8-, CD4- CD8+ and CD16- CD57+ cells. Removal of plasma from whole blood also reduced the fluorescence intensity of CD4 and CD5 antigens and increased that of CD8, CD16, CD19 and CD57 antigens on each lymphocyte subsets. Characteristics of the changed lymphocyte subsets were to have a surface antigen with weak immunofluorescence on the flow cytometric analysis such as CD5 and CD16, and to have an unclear borderline between the positive and negative cells. Therefore, even slight changes in the fluorescence intensity of these antigens could change the proportion of CD5+ CD19+, CD16+ CD57- and CD16+ CD57+ cells. However, these changes were not observed, when using the washed blood cells as samples after readdition of plasma to them. These data suggest that removal of plasma from blood before labelling the lymphocytes with fluorescein-conjugated antibodies is necessary to make the sample condition equal for flow cytometric analysis of lymphocyte subsets. PMID- 1762200 TI - [von Willebrand factor multimer analysis using electroblotting and immunoperoxidase staining method]. AB - Further modification of the previously reported peroxidase staining method for von Willebrand factor (vWF) multimer is described in this article. The alteration are as follows: affinity purified anti-human vWF rabbit IgG was replaced by commercial anti-human vWF rabbit IgG, and washing and reaction steps were shortened markedly. Despite these modification, the resolution of vWF multimers on the nitrocellulose membrane remains comparable to the autoradiography. However, unlike autoradiography, results produced by this method can be obtained in a day. The features of this method are especially useful in clinical laboratories where both time and equipments are limited. PMID- 1762201 TI - [Significance of determination of the blood antibody level in Chlamydia trachomatis infection of the uterine cervix]. AB - Kits for measurement of C. trachomatis specific antibody are not commercially available, but of the significance of determination of the serum antibody level has not been clarified. In this study, we first determined the C. trachomatis antibody level in patients considered to be free of C. trachomatis infection. Then, we evaluated the relationship between the presence or absence of antigen with the antibody level in patients at our department who were available for antigen examination. Anti-C. trachomatis IgA and IgG antibodies were detected in all age groups with a peak frequency in the 20's expect that IgA antibody was absent in the umbilical blood (IgG antibody was detected also in the umbilical blood). Concerning the relationship between the presence or absence of C. trachomatis antigen and the serum antibody levels, both IgA and IgG antibodies were significantly different (chi 2 test, p less than 0.01) between the antigen positive group and the antigen-negative group. Because females infected by C. trachomatis were more often asymptomatic than infected males, and because antigen tests may produce false negative results, determination of the antibody level must be included in the clinical tests. Determination of the antibody level is considered to be valuable also in screening for mother-child infection and asymptomatic infection. PMID- 1762203 TI - Proceedings of the 24th annual meeting of the Japan Epilepsy Society and the Japanese Branch of the International League Against Epilepsy. November 16-17, 1990, Okinawa. PMID- 1762202 TI - [Mixed type cryoglobulinemia with discrepancy of platelet counts measured with an automated cell counter and by manual counting method]. AB - We experienced an abnormal blood sample which showed larger numbers of white blood cells and platelets counted by the electric resistance system and of platelets in mechanical counting by the flow system, than those in manual counting. Many precipitates were observed in this blood sample at room temperature or 4 degrees C, but were not observed at 37 degrees C. The precipitates were clarified to be caused by the mixed type (IgA, IgG and IgM) cryoglobulin by using an immunofluorescence method and an ouchterlony method. These data indicate that precipitation of cryoglobulin at room temperature induce falsely high value of platelet count in mechanical counting systems. PMID- 1762205 TI - The role of interhemispheric pathways in generalization of kindled seizures in cats and subhuman primates. AB - The role of interhemispheric pathways in generalization of partial seizures was evaluated in the kindling model of epilepsy. The generalized seizure kindled from the amygdala was asymmetrical in cats with callosal bisection, destruction of massa intermedia of the thalamus or bilateral ventral hippocampus. The generalized convulsion of amygdala kindled cats became asymmetrical or changed into partial seizures by callosal bisection. The fully-kindled amygdala seizure of a split-brain epileptic baboon and rhesus monkey was a hemiconvulsion or an asymmetrical generalized convulsion. The amygdala-kindled bisymmetrical generalized convulsion of the epileptic baboon was changed into a hemiconvulsion or an asymmetrical generalized convulsion. These results indicate that the corpus callosum plays an important, although not exclusive, role in bilateralization of epileptic activity, and its role becomes more important when the animal ascends the phylogenetic scale. PMID- 1762204 TI - Surgical treatment of epilepsy. PMID- 1762206 TI - Propagation of acute seizure activities observed by local cerebral glucose metabolism. AB - We studied the propagation of acute focal seizure activities in animals by means of the [14C]deoxyglucose method. Seizures were induced unilaterally by injecting penicillin in the neocortical area 4 and area 9 in the monkey, and by injecting kainic acid in the hippocampus of the rat and in the ventral posterolateral thalamic nucleus of the cat. The earliest and the most consistent propagation was the one to the target structures of the primary focus, mediated through the "preferential" projection pathways. At a more advanced stage, the propagation to the immediately adjoining brain regions occurred, followed by the secondary propagation to the target structures of the adjoining regions. Propagation to the contralateral homologous structure was not a major one at the early stage unless the structure of the primary focus had its own commissural connections. PMID- 1762208 TI - Epilepsy and driving licence in the Federal Republic of Germany and other European countries. PMID- 1762207 TI - Mechanism of electrographic seizure generation in the rat brain slice in low magnesium medium: modulatory effect of interictal bursting on seizure generation. AB - In order to understand the mechanisms underlying seizure generation, the present study investigated the functional and anatomical interaction between seizures and interictal bursts. Bathing rat brain slices of the hippocampus and entorhinal cortex in zero magnesium medium elicited electrographic seizures. In the later period, the electrographic seizures were eventually replaced by the interictal bursts. In this phase, lowering [K+]o and raising [Ca2+]o restored the tonic seizures by suppressing the interictal bursts. A multiple knife cut experiment revealed that the seizures arose in the entorhinal cortex and the interictal bursts originated in CA3. A selective knife cut across the subiculum showed that the interictal bursts, propagating from CA3 to the entorhinal cortex, disrupted and suppressed the electrographic seizures in standard Mg(2+)-free medium. PMID- 1762209 TI - Driving and epilepsy: a prospective questionnaire survey in Japan. Committee on Driver's Licenses, the Japan Epilepsy Society, Shizuoka. PMID- 1762210 TI - A study on driving status in 98 epileptic patients with driving licences. AB - As to the driving status in the period between January 1984 and December 1988, 98 epileptic patients with driving licences were examined, paying regard to their clinical conditions. Sixty-one (62%) of the patients were seizure-free for the last five years or more in December 1988. Eighty-one (83%) were actually driving motor vehicles at the time of this study, and 27 (33%) of the 81 drivers still had fits during the past five years. Nine patients (9%) had caused traffic accidents, but no accident had occurred due to seizures. The type of the nine accidents was as follows: One case of a slight physical injury to the other person, four cases of the driver's own car damage without other material damage, and four of the accidents involving other cars. PMID- 1762211 TI - Epilepsy and driving: a survey of automobile accidents attributed to seizure. AB - From results of a survey of 72 epileptic car drivers who had a mean driving history of 8.6 years, 18 (25%) had experienced one or more automobile accidents ascribed to a seizure while driving, with the total number of accidents of the surveyed group amounting to 35. All the drivers were known to have partial epilepsy, 13 of them having temporal lobe epilepsy. The main characteristics of these 35 accidents were as follows: (1) Fifty-seven percent were caused by complex partial seizure without an aura in which consciousness was immediately impaired at onset, while about 10% were attributed to simple partial seizure in which the conscious state was not altered. No accident was caused by a first seizure; (2) Fifty-one percent occurred on an empty road with little pedestrian and/or vehicular traffic; (3) In about half the accidents, the driver's vehicle collided against an immovable object, and only 20% involved crashing into another car; (4) Most accidents caused damage to only the driver's car and/or mild physical injury; and (5) Fifty-four percent of the accidents were not reported to the police, and many that were reported were ascribed to driving while asleep, to careless driving or to similar behavior. PMID- 1762212 TI - Discussion on the 'problem of driving license for people with epilepsy'. AB - From the socio-medical points of view, the problem of a driving license for people with epilepsy was discussed. It was concluded that not only seizure but also the presence of side-effects of drugs and of personality change should be assessed to allow them the license. Finally, a medical guideline was proposed for the driving license for people with epilepsy. PMID- 1762213 TI - Classification of epilepsies, epileptic syndromes and related seizure disorders (1989): an outline and the use. PMID- 1762214 TI - Usefulness of the newly proposed International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders (1989): a trial on adult patients in a neuropsychiatric clinic. AB - The utility of the "International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders," proposed by ILAE in 1989, was investigated in a neuropsychiatric clinic with a patient population numbering 300. Two hundred and three patients (67.7%) had localization-related epilepsies (LRE), including one idiopathic case. Sixty-six patients (22%) had generalized epilepsies, 50 idiopathic, 2 Lennox-Gastaut syndrome, and 14 symptomatic. Thirty one patients (10.3%) with generalized tonic-clonic seizures occurring only during sleep had the epilepsies undetermined whether they are focal or generalized. In the symptomatic LRE cases, 34 cases could not be classified, and 7 of the cases with frontal lobe epilepsies were difficult to subtype. Eleven of the symptomatic LRE cases had some independent seizures, multiple foci in surface EEGs and were intractable. These cases may be defined as "multifocal epilepsies." PMID- 1762215 TI - A new method for determination of motor cortex by electrical stimulation under general anesthesia: evaluation of its reliability. PMID- 1762216 TI - Multiple subpial transection (MST) for the control of seizures that originated in unresectable cortical foci. AB - Multiple subpial transection (MST) was applied to 12 cases with intractable epilepsy, the foci of which were located in unresectable essential areas. The result proved that MST is effective in controlling seizures, and no explicit neurological deficits have incurred postoperatively. PMID- 1762217 TI - Monotherapy for childhood epilepsies with zonisamide. AB - Zonisamide was tried on 44 children, 18 girls and 26 boys, from 8 months to 15 years of age at the start of the trial. In 6 children the drug has been stopped because of side effects. The drug was introduced at a dose of 2-4 mg/kg/day and increased to 12 mg/kg/day unless a satisfactory response occurred at a lower dose. A 100% control of seizures was achieved in 5 of 5 cases of idiopathic generalized epilepsies, in 7 of 8 cases of symptomatic generalized epilepsies, in one of one case of idiopathic partial epilepsies, and in 17 of 24 cases of symptomatic partial epilepsies. The main side effect was drowsiness, especially during the introduction. PMID- 1762218 TI - 10-year follow-up study of epilepsy with psychosis. AB - Thirty-three cases of psychosis associated with epilepsy were followed in our clinic for 10 years. In 12 cases, the psychotic symptom appeared episodically and 9 of them had more than one relapse and 7 of them more than 2 relapses. Only 3 cases had no relapse. In 21 cases, the psychotic symptoms were continuous, lasting more than 2 years. In 8 of them, the symptoms were stable and remained unchanged but in 13 of them, the symptom showed exacerbation and partial remissions. In 11 cases, a decrease or discontinuation of antipsychotic drugs (mostly haloperidol) significantly provoked or aggravated the psychotic symptoms. PMID- 1762219 TI - Correlation of subclassification of temporal lobe epilepsies with performance rate of WAIS. PMID- 1762220 TI - Biochemical abnormalities in developing E1 mouse. AB - Complex biochemical abnormalities were found in the early developmental stage of the E1 mouse. First, the E1 mouse has abnormal levels of specific amino acid concentration within a week from birth. Second, an unusual expression of poly(A)+ RNA from the one-day newborn liver of the E1 mouse was detected by use of Cot 100 DNA as a probe. Third, sodium channels are increased in synaptosomes and at the mRNA expression level of the 3 or 4-week-old E1 mouse brains, compared with the ddY mouse. These results suggest that the biochemical abnormalities described in this study may affect greatly the epileptogenesis of E1 mouse. PMID- 1762221 TI - Cerebral metabolic changes induced by antiepileptic drugs: a sequential double label deoxyglucose study. PMID- 1762222 TI - Effect of adenosine agonist (propentofylline) on rat hippocampal seizures induced by microdialysis with potassium: analysis using compressed EEG power spectrum array. PMID- 1762223 TI - Roles of a subependymal nodule of tuberous sclerosis on pathophysiology of epilepsy. AB - Polysomnographies (PSG) were performed on two cases with tuberous sclerosis (TS), both having subependymal nodules on the medial wall of the caudate nucleus adjacent to the thalamostriatal sulci. Clinically one had suffered from infantile spasm and which later turned out to be complex partial seizure with a rotation toward the right. The other had developed tonic seizure on the right with a rotation toward the left in early childhood. Clinico-pharmacological studies revealed the existence of synaptic supersensitivity of the dopamine (DA) receptor in the left caudate and PSG confirmed the synaptic supersensitivity of the former, while in the latter case, it suggested a decrease in DA activity on the left. Subependymal nodules in the caudate nucleus could cause a reduction in the DA transmission and develops synaptic supersensitivity after suffering from TS. PMID- 1762224 TI - A case of localization-related epilepsies suspected of panic disorder. AB - Some localization-related epilepsies have autonomic symptoms as well as psychic symptoms. As these symptoms are similar to those of panic disorder, it is important to discriminate between the two disorders. In such cases, VTR polygraphic examination is necessary for the correct diagnosis. PMID- 1762225 TI - A video-EEG study of astatic seizures observed in patients with myoclonic astatic epilepsy of early childhood (Doose syndrome). PMID- 1762226 TI - Effects of intraamygdaloid injection of taurine and valyltaurine on amygdaloid kindled seizure in rats. AB - Antiepileptic effects of intracerebral injections of taurine and valyltaurine were examined in amygdaloid kindled rats. The effects were assessed whether the animals can evoke generalized seizures by a 10 microA higher stimulation intensity than triggering thresholds. In all fully-kindled animals that have received intraamygdaloid injection of 500 nmol taurine, the kindled seizure was completely abolished. Such a significant seizure suppression (p less than 0.05) was observed 12-24 h after the taurine injection. Valyltaurine (500 nmol) also suppressed the seizure in 60% of animals tested, but the effect was not statistically significant. The results indicate that taurine may effectively suppress epileptic seizures when it acts directly at the stimulation site amygdala. PMID- 1762227 TI - Effects of immobilization stress on hippocampal interictal discharges in hippocampal kindled rats. PMID- 1762228 TI - Afferent connections of the neurons in the Forel's field of H in cat. AB - An anatomico-physiological analysis was made to elucidate afferent connections of the neurons in the Forel's field of H (FFH) by horseradish peroxidase retrograde tracing technique and by evoked potential technique. 1) The FFH neurons receive fibers from the neocortex (layer V) and brainstem reticular formations. 2) Physiological projections from the mesencephalic reticular formation to the FFH as well as to the motor cortex were ipsilateral, but those from the pons and medulla oblongata were bilateral. 3) These data will suggest that the FFH neurons are in junction of the cortico-reticular connections and play an important role in the maintenance of an epileptic excitability of the neocortical system as suggested by Jinnai and Mukawa. PMID- 1762229 TI - Kainic acid microinjection into a unilateral occipital cortex or lateral geniculate body in unanesthetized cats: models of generalized epilepsy and photic epilepsy. PMID- 1762230 TI - Cerebral glucose metabolism in epilepsy patients associated with organic brain damage. PMID- 1762231 TI - Single photon emission computed tomography (SPECT) in patients with periodic lateralized epileptiform discharges (PLEDs). PMID- 1762232 TI - Reversal of MRI lesion with relapse and remission of partial motor seizures in epilepsia partialis continua. PMID- 1762233 TI - EEG findings in offspring of epileptic mothers. PMID- 1762234 TI - Severe myoclonic epilepsy in infancy: a long-term follow-up study. PMID- 1762235 TI - Clinical features and prognosis of complex partial seizures appearing in the first three years of life. PMID- 1762236 TI - An electroencephalographic study on withdrawal of antiepileptic drugs in children with epilepsy. PMID- 1762237 TI - Clinical course of epilepsy with continuous spike-waves during slow wave sleep. PMID- 1762238 TI - A morphological study on MRI in 100 patients with epilepsy. PMID- 1762239 TI - P300 in epileptic children: cognitive effects of antiepileptic drugs. PMID- 1762240 TI - A clinico-electroencephalographic study of intractable generalized epilepsy in childhood. PMID- 1762241 TI - Multicystic encephalomalacia in an adult case of Lennox-Gastaut syndrome: a case report. AB - It is well known that multicystic encephalomalacia results in a severe neurological deficit and psychomotor retardation. The authors reported the case of a 30-year-old man with Lennox-Gastaut syndrome who had multicystic encephalomalacia in CT and MRI but whose neurological deficit was not serious. It is possible that the forceps delivery caused MCE and that a vaccination against Japanese encephalitis at the age of 9 triggered the Lennox-Gastaut syndrome. PMID- 1762242 TI - Two cases with epilepsy who manifested manic-depressive symptoms under barbiturates treatment. PMID- 1762243 TI - Asymmetry of eye fixations in temporal lobe epileptics: analyzed by eye mark recorder. PMID- 1762244 TI - Epilepsy population and their care problems in sheltered day-service institutions for the mentally retarded in Tokyo District: a preliminary report. PMID- 1762245 TI - A case of age dependent epileptic encephalopathy with CT appearance and neuropathological findings. PMID- 1762246 TI - Myoclonic astatic epilepsy presenting eyelid myoclonic seizures induced by closing of eyes. AB - A male infant with myoclonic astatic epilepsy showed myoclonic seizures of the eyelids by closing of the eyes. There was no photosensitivity in EEG with flash stimulation and he could induce seizures even in total darkness. The latency between a lid closure and onset of seizure discharges on EEG was relatively long (0.3-0.5 second). Epileptic seizures in this patient may be induced via a brainstem reticular formation, and elevated Bell's position seems to be the necessary stimulus to produce seizures. PMID- 1762247 TI - Epilepsy associated with hemiplegia: 1. Seizure manifestations. AB - 1. The seizure manifestations of patients with hemiplegia were reminiscent of partial seizures. The motor manifestations were notably asymmetrical and impairment of consciousness was mild. Nevertheless, tonic seizures, identified by electroclinical correlation were found in 49 patients (88%) although they were predominantly unilateral or asymmetrical. 2. Unclassified seizures characterized by ictal automatisms, which mimic complex partial seizures was observed in 5 patients (9%). 3. Late epileptic seizures of the HHE syndrome were regarded as psychomotor seizures by Gastaut et al. In the present study, however, complex partial seizures were found in only 3 at 28 patients with HHE syndrome (11%) whereas tonic seizures in 23 of these patients (82%). One possible reason for this discrepancy is bias in the selected patient population, because those with transient hemiplegia were not included, and infrequently occurring partial seizures might have been missed. Further study is therefore needed to determine whether the HHE syndrome is associated with complex partial seizures or predominantly unilateral tonic seizures. PMID- 1762248 TI - Multielemental analysis of hair in patients with epilepsy, with special reference to the clinical significance of hair in patients with hypocalcaemia. PMID- 1762249 TI - Studies on pharmacoepidemiology of antiepileptic adverse reactions (2). PMID- 1762250 TI - The effects of clonazepam on rolandic discharge of benign epilepsy of children with centro-temporal EEG foci. AB - 1) CZP had marked effects on RD. RD disappeared in 8 (73%) of 11 patients treated with CZP alone and 6 (43%) of 14 treated with CZP in combination with other drugs. Even when RD persisted, its amplitude and frequency decreased in some patients. 2) In the group treated with CZP in combination with other drugs, RD disappeared in all 5 patients with the persistent RD, of whom 2 had arachnoid cyst. Of the 6 patients with frequent seizures, 2 were subsequently diagnosed as having CPS and SPS, respectively. Patients who did not respond to CPZ included those in whom the diagnosis of BECCT should be reconfirmed, and electro-clinical response may be also useful for diagnosing RD. 3) In patients treated with CZP alone for a short-term treatment of BECCT, the drug administration could be discontinued only in one. A longer follow-up study is necessary to reach a conclusion in future. PMID- 1762251 TI - The long-term effectiveness of clonazepam therapy in the control of partial seizures in children difficult to control with carbamazepine monotherapy. PMID- 1762252 TI - Influence of concurrent administration of sodium valproate on the plasma concentrations of carbamazepine and its epoxide and diol metabolites. PMID- 1762253 TI - Teratogenicity of antiepileptic drugs: is the prevention possible? AB - To assess the relative contribution of antiepileptic drugs (AEDs) toward the occurrence of congenital malformation, two prospective studies (previous and present) were compared. In the present subjects of 145 cases, the total daily dose of AEDs (drug score) in each case was decreased as much as possible, and polypharmacy was changed to monopharmacy before conception where it was possible. The incidence of malformations significantly decreased from 13.5% to 6.2% (p = 0.031) by the change in drug regimen. The drug score, number of AEDs, maternal age at delivery, seizure type, and etiology of epilepsy were statistically different between the two study groups. Even after the correction of the data by the last three factors, the difference in the incidence of malformation did not disappear, while it disappeared if data were corrected either by the drug score or number of AEDs. These results suggest that the possibility of prevention of AED related malformations is possible by an improvement in AED therapy. PMID- 1762254 TI - Clinico-electroencephalographical study on temporal lobe epilepsy. PMID- 1762255 TI - A case of epilepsy characterized by spike-wave stupor followed for long period. AB - A 34-year-old housewife with nonconvulsive status epilepticus was followed up for 20 years since the initial fit. She maintained some contact with reality during the stupor and recalled the episode to some extent, while the EEG showed continuous spike-wave complexes. During the clinical course, the main type of seizures was spike-wave stupor, of which the maximum frequency was several times a week in the hospital and the duration was many minutes to several hours, and also secondarily generalized convulsive seizures occurred approximately once a month. The lasting control of spike-wave stupor was not achieved in spite of the various medications for the long follow-up period. The ictal EEGs of spike-wave stupor always showed the frontal origin. The meaning of the term "nonconvulsive status epilepticus" in this case was briefly discussed. PMID- 1762256 TI - Schoolchildren with epilepsy: epidemiological and longitudinal studies on questionnaire for teachers at intervals of 12 years. PMID- 1762257 TI - Social adjustment of epileptic patients with psychiatric symptoms. PMID- 1762258 TI - Dopamine and basal ganglia. PMID- 1762259 TI - Neuronal transplantation in parkinsonism. PMID- 1762260 TI - Central dopaminergic neurons: immunohistochemistry and in vivo monitoring of dopamine release correlated to behavior. PMID- 1762261 TI - [Acid phosphatase as tumor marker of prostatic cancer]. AB - Prostatic cancer was the first malignancy in which tumor markers could be used to follow the response to therapy or progression of the prostate cancer. The use of these tumor markers has been of significant clinical value in diagnosis and follow-up of patients. Over the years, significant technical improvements have been made on the sensitivity and specificity of the assays for prostatic acid phosphatase. PMID- 1762262 TI - [The effects of gravity load on the canine kidney]. AB - In Self-defense Force Hospitals we often treat pilots with renal stones who will be exposed to high gravity (G) load after the treatment. Because the regulation prohibits the flight of a pilot with urolithiasis, the stone must be removed completely by noninvasive procedure. Percutaneous nephrolithotomy, therefore, is one of the treatment of choice in such patients. The effect of G load on the kidney, in particular, on the renin-angiotensin-aldosterone (R-A-A) system and the safety of percutaneous nephrolithotomy in a pilot who is exposed to high G load have not been adequately investigated. In this study, I examined the effect of G load in canine kidney model. The effect of G load on R-A-A system: Twenty two adult mongrel dogs of a mean weight of 10.9 kg. maintained on a normal Na+ intake were studied. To dogs in the sitting position, high G load was given. The exposure to G load consisted of maximum load of 8 G for 45 seconds with the onset ratio of 0.1 G/sec. for group 1, and 5 courses of maximum G load of 8 G for 10 seconds with the onset ratio of 2.5 G/sec., followed by 1.5 G for 60 seconds for group 2. Plasma renin activity was unchanged in group 1, but it increased in group 2. Plasma aldosterone increased from 68.6 +/- 17.9 to 252.0 +/- 56.4 pg/ml (p less than 0.005) in group 1. and from 191.8 +/- 40.6 to 479.2 +/- 76.0 pg/ml (p less than 0.005) in group 2 after G load. Angiotensin II decreased from 129.0 +/- 19.4 to 84.7 +/- 19.1 pg/ml (p less than 0.05) after G load in group 2. These data suggest that the increase in plasma aldosterone after G load in independent of the renin-angiotensin system. It is considered that the alteration of R-A-A system was caused by the change of blood flow distribution due to the effect of G load. The tolerance to G load on the kidney following subcutaneous nephrostomy: Unilateral subcutaneous nephrostomies were carried out under pentobarbital anesthesia in 15 adult female mongrel dogs. Each experimental dog was exposed to high G load 2 or 4 weeks after removal of the nephrostomy tube. Excretory urography, renal angiography and renal function tests were performed before and after G load. Excretory urograms demonstrated no remarkable changes at all after G load in all dogs. Renal angiograms revealed small renal infarction along the nephrostomy tract in almost all dogs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762263 TI - [Correlation between the prostatic vessels and vertebral venous system of the dog]. AB - We examined the correlation between the intrapelvic vessels, especially prostatic vessels, and the vertebral venous system in the male dog by radiography. Aorta abdominalis branches the right and left external iliac arteries at the 6th lumbar vertebra, and is divided into the right and left internal iliac arteries and arteria sacralis mediana at the 7th lumbar vertebra. Arteria urogenitalis arises from the internal iliac artery at the middle of articulatio iliosacralis, and is divided into arteria vesicalis caudalis cranially and arteria prostatica caudally. Arteria prostatica is divided in the prostatic capsule and distributed to the prostatic parenchyma in which arteries form the network. Vena prostatica is distributed to the prostatic parenchyma, forming the network and entered vena urogenitalis after joining vena vesicalis caudalis. Vena urogenitalis joins the internal iliac vein, and then the common iliac vein and vena cava posterior after joining the external iliac vein. The anastomosis between the intrapelvic vein and the vertebral venous system is formed by the vena intervertebralis. The vertebral venous system is anastomosis with the vena cava posterior, the common iliac vein, the internal iliac vein and vena pudenda interna. PMID- 1762264 TI - [An enzymatic determination of serum citrate with citrate lyase]. AB - A method for the enzymatic determination of the serum citrate using citrate lyase is described. The optimum pH was equal to or higher than 8.6. Prior to the determination of the serum citrate, the samples were deproteinized with perchloric acid. After the precipitation of the proteins, potassium hydroxide was added under an ice-cooling condition in order to neutralize the solution. The recovery rates of the citrate added to serum ranged from 92% to 108%, and the coefficient of variation of triplicate assay was 4.2%. The mean serum value of 17 healthy subjects was 1.57 mg/dl, with a range of 1.03-2.03 mg/dl. In seven healthy subjects, 3 g of sodium-potassium citrate was administered orally and the serum citrate was measured 0, 15, 30, 45, 60, and 120 min later. The serum citrate was significantly increased in the periods between 15 and 60 min. PMID- 1762265 TI - [Ureteral function at the ureterovesical junction. Action potentials of the canine intramural ureter during bladder filling or bladder contraction]. AB - The relationship between bladder movements and the intramural ureter was studied in the dog by recording electromyograms of the intramural and extravesical ureters recorded during bladder filling and contraction. Bladder filling was achieved by instilling physiological saline at a rate of 10 ml/min to a volume of 5 ml/kg, while bladder contraction was induced by electrical stimulation. For electromyography, an electrode was inserted transperitoneal into both the extravesical ureter and the intramural ureter after it had been separated from the extravesical ureter. A cystostomy for the instillation of water and another cystostomy for the measurement of intravesical pressure were also made in the bladder. During bladder filling at an intravesical pressure of about 10 cmH2O, the frequency of the action potentials in the intramural ureter showed no significant difference to those in the extravesical ureter. In addition, during bladder contraction at a greatly increased intravesical pressure of about 5 times the precontraction level, the frequency of the action potentials in the intramural ureter was not significant by different from those in the extravesical ureter, and also from its own precontraction value. The above findings suggest that action potentials in the intramural ureter are not affected by bladder movements such as filling or contraction, and that the ureter continues to actively transport urine to the bladder during such movements. PMID- 1762266 TI - [A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer]. AB - Retrospective study on the frequency of associated bladder cancer and the influence on the prognosis was carried out in 170 cases of renal pelvic and ureteral cancer. The number of cases of associated bladder cancer coexistent with renal pelvic and ureteral cancer was 31 (18.2%), and the number of subsequent cases 3 (19.4%). The frequency of occurrence of the primary tumor site was 27.2% in the renal pelvis, 45.6% in the ureter and 58.3% in both renal pelvis and ureter. Multiple tumors occurring in the renal pelvis and ureter occupy a high percentage. As for the degree of differentiation, many cases were subsequent to G1. As for the stage, a few cases with bladder cancer were subsequent to T4, but there was no definite tendency in the occurrence of bladder cancer. The prognosis of renal pelvic and ureteral cancer: the 10-year survival rate was 93.3% for G1, 66.6% for G2 and 12.4% for G3. As can be seen, there was good correlation with the pathological gradings. It must be remembered, however, that 5-year survival rates in cases of associated bladder cancer of coexistent type, in cases of subsequent type and in cases without associated bladder cancer were 56.2%, 72.7% and 64.8%, respectively: there was no significant difference. Bladder cancer associated with renal pelvic and ureteral cancer makes the therapy troublesome, but no influence on the prognosis was observed. Therapy in conformity with the pathological grading and stage is regarded as particularly important in cases of associated bladder cancer. PMID- 1762267 TI - [Studies on renal damages after extracorporeal shock wave lithotripsy using Gd DTPA-enhanced dynamic MRI]. AB - Renal damages after ESWL treatment were examined by Gd-DTPA enhanced dynamic MRI. Gd-DTPA was used as the contrast medium and fast magnetic resonance imaging with suspended respiration using the flip angle of 20 degrees and gradient echo technique at 0.5 Tesla was used for photographing. In normal kidneys, a low intensity band was observed with the passage of Gd-DTPA through the kidney from 1 to 2 minutes after the injection. In patients who underwent ESWL treatment, however, the low intensity band which was observed before ESWL treatment became partly obscure after ESWL treatment. Furthermore, these find changes in the renal parenchyma could not be fully detected by usual MRI which does not use Gd-DTPA. Gd-DTPA enhanced dynamic MRI was considered to be effective for finding the limited dose of shock waves for ESWL treatment. PMID- 1762268 TI - [Lymphocytic subsets of tumor tissue, non tumorous kidney, and the peripheral blood in primary renal cell carcinoma]. AB - Lymphocyte subsets were examined in renal cell carcinoma (TILs), adjacent non tumor renal tissue and peripheral blood (PBLs) by flow cytometry and histochemistry in eighteen patients with renal cell carcinoma. CD5-positive cells were predominant in the TILs in 14 patients. In the renal cell carcinoma tissue, CD8-positive cells were predominant over CD4-positive cells, resulting in a less than unity ratio of CD4/CF8-positive cells. The lymphocyte number was significantly in adjacent normal renal tissue than in renal cell carcinoma. However, lymphocyte subsets ratios were not significantly different between these two tissues. PBLs showed the same proportions (CD4/CD8 mean 1.9 +/- 0.8) as the previously published healthy controlled data. The proportions of CD8-positive cells were significantly increased (p less than 0.05) and those of CD4-positive cells were also significantly decreased (p less than 0.01) in the TILs. The infiltrating pattern of TILs in 17 patients was divided histochemically into cluster (N = 7), single (N = 4), and mixed types (N = 6). The cluster and mixed types were significantly more common in grade 1 tumors and the single type was more common in the grade 2 tumors (p less than 0.05). The pT3 tumors showed the single type of TIL infiltration pattern, but showed no significant difference. In the cluster pattern of TILs, CD8-positive cells were surrounded by CD4-positive cells. Non-tumorous kidneys showed no infiltration of lymphocytes, except in 2 patients of pyelonephritis. These results suggest that cytotoxic T-cells stained as CD8 play an immunoreactive role against renal cell carcinoma. PMID- 1762269 TI - [Immunological study on renal cell carcinoma in dialysis patients with acquired cystic disease of kidneys]. AB - The immunological study of the major histocompatibility complex (class I, class II and DR antigens), tumour infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) was evaluated on the basis of immunohistochemical staining using monoclonal antibodies of each subset of lymphocytes in a series of 16 patients with renal cell carcinoma. Two renal cell carcinomas in dialysis patients with acquired cystic disease of the kidneys (ACDK) were also included in this study. With regard to the immunological environment, a comparative study between renal cell carcinoma accompanied with ACDK and 14 other renal cell carcinoma was carried out. The results are described below: 1) With regard to the expression of MHC antigens in tumour cells, the degrees of expression of MHC class I, class II and DR-antigen in case 1 were higher than that of the other 14 renal cell carcinomas. On the other hand, no expression of MHC was detected in case 2. 2) As to the subsets of TIL, the CD25 (IL-2 receptor) was not expressed in all the renal cell carcinoma. As to the T cell receptor (TCR-alpha/beta chain), the degree of expression was the same in case 1 and the other 14 cases. On the other hand, no TCR was detected in the case 2. As to the other subsets of TIL (CD3, CD4, CD8, CD16 and CD20), the rates of the infiltration were the same in case 1 and the other 14 cases, but those in case 2 were lesser than in all other 14 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762270 TI - [Urethral indwelling catheter, intermittent self-catheterization and urinary infection]. AB - Once a catheter has been passed into the bladder without contamination, there are several possible routes of subsequent infection during drainage period, such as: 1. Entry of bacteria alongside the catheter in the urethra. 2. Introduced bacteria adhered easily to the indwelling catheter and drainage system and colonized. 3. The catheter tip is covered rapidly by various nutrient materials which becomes a good culture medium of stuck bacteria, which is a supply source of bacteria into the bladder urine. 4. Although the motile bacilli ascend very slowly through the stagnant tube and no bacteria ascend against a slowly moving column, rapid transport of organisms occurs in the swirling fluid caused by the passage of rising air bubbles. 5. Continuous urethral catheter drainage permits an average residual urine volume of 7.3 ml. 6. The catheter destroys the antibacterial defense mechanisms of the urinary bladder. The reasons why in many cases of intermittent self-catheterization (CID) urine becomes sterile despite non-sterile procedure, are as follows. In addition to that CIC has none of the disadvantages of the indwelling catheter, it improves the vesical defense mechanisms deteriorated by high pressure voiding. The number of bacteria reintroduced during catheterization is relatively small and they can be eradicated by usual scheduled catheterization within 4-5 hours without residual urine. CIC must be started before trabeculation or diverticuli are formed, in which bacteria remain. Actual determination of residual urine volume after catheterization will help to prescribe a rational program of CIC. PMID- 1762271 TI - [Gram-positive cocci in the urinary tract. Do they influence the postoperative course of transurethral prostatectomy?]. AB - The influence of gram-positive cocci on the postoperative course of transurethral prostatectomy was analysed on 463 patients. The half of isolated cocci was Enterococcus, followed by S. epidermidis and S. aureus. The rates of postoperative urinary infection by gram-negative bacilli were nearly the same for patients with preoperative gram-positive cocci infection and those without any of bacteria (3/79 vs. 9/310). Patients who developed new infection with gram negative bacilli had fever, in contrast to patients with new gram-positive cocci infection. Gram-positive cocci prolonged the postoperative pyuria but not so long as gram-negative bacilli. All these findings suggest that infection caused by gram-positive cocci is not so severe as that caused by gram-negative bacilli. PMID- 1762272 TI - [Correlation of atypical hyperplasia and latent carcinoma of the prostate]. AB - Atypical hyperplasia and latent carcinoma of the prostate from 310 prostates of all age obtained at autopsy were studied. Atypical hyperplasia was graded into 3 groups based on the frequency of nucleoli and cell arrangement. The results were as follows: the origin of both atypical hyperplasia and latent carcinoma was considered to be in the peripheral zone. The frequency of atypical hyperplasia increased with age. Atypical hyperplasia was found in younger generation than latent carcinoma. Grade of atypical hyperplasia increased with age. Atypical hyperplasia was often coincident with latent carcinoma: 74% of atypical hyperplasia were associated with latent carcinoma. Atypical hyperplasia was significantly associated with multicentric latent carcinoma. All these findings supported the assumption that atypical hyperplasia was a premalignant lesion. Clinically, in a case in which atypical hyperplasia is found in biopsy, intense follow-up will be necessary. In particular, in cases of grade 3 atypical hyperplasia, further study for detection of probable coexistent carcinoma is recommended. PMID- 1762273 TI - [Pulsatile administration of LH-RH for hypogonadotropic hypogonadism]. AB - A case of hypothalamic-pituitary failure is reported. A 28-year-old man who had been treated with testosterone for hypogonadism for two years was admitted to our hospital with the chief complaint of sexual problems. The serum level of gonadotropins was very low and hypophysial responses to luteinizing hormone releasing hormone (LH-RH) were good. Treatment was started with subcutaneous pulses of 10 micrograms LH-RH every 120 minutes using a portable infusion pump. Gradually, his potency improved and ejaculation returned. The serum concentration of FSH, LH and testosterone increased to the normal range of adult males and the testicular volume increased rapidly from 5 ml to 14 ml after 13 weeks of treatment. Sperms appeared in the ejaculated fluid after 25 weeks and, after following 16 weeks, the concentration of sperms increased up to 20 x 10(6)/ml. Prolonged pulsatile subcutaneous administration of a low-dose of LH-RH at a physiologic frequency was an effective therapy for pubertal induction and maturation in hypogonadotropic hypogonadism due to hypothalamic-pituitary failure. PMID- 1762274 TI - Self-nurturance: the nurse needs it also. PMID- 1762275 TI - Nursing directed health care with the homeless population. PMID- 1762276 TI - Rx for good relations with graduate nurses. PMID- 1762278 TI - Tips for self-nurturing: priorities, models and axioms. PMID- 1762277 TI - Simple tools for self-nurturance. PMID- 1762279 TI - [Left ventricular systolic function in young women with hyperkinetic syndrome- echocardiographic evaluation]. AB - In twenty two young (mean age 31.6 years) normotensive women with hyperkinetic heart syndrome (HHS) we assessed echocardiographically left ventricular (LV) function indexes before and after 40 mg of oral propranolol. At baseline the HHS group differed from controls with respect to higher heart rate heart and diastolic blood pressure (BPs), lower systolic and systolic LV volumes, greater corrected mean circumferential fiber shortening, ejection fraction, cardiac index and contractility index (systolic blood pressure x body surface area/LV end systolic volume ratio). Propranolol normalized nearly all analyzed indexes except for BPs which remained increased compared to controls. In young women with HHS enhanced cardiac performance is expressed by higher cardiac index and speed of blood ejection from the left ventricle, is related to tachycardia and higher contractility but not to increased preload. Results post propranolol administration speak in favour of significant role of increased beta-adrenoceptor stimulation in HHS. PMID- 1762280 TI - [Acute myocardial infarction. Analysis of the activities of the ambulance "R"]. AB - Frequency of emergency calls for ambulance help to patients with acute myocardial infarction (MI) as well as a number of infarct complications and the influence of immediate professional help on survival of prehospital phase of acute MI is reviewed. The diagnosis of acute MI was based on a typical history of chest pain and electrocardiographic findings. Acute MI was also diagnosed in all cases of sudden cardiac death. Out of 3674 calls for ambulance help, MI was diagnosed in 379 patients what amounts for 10.1% of all interventions in life-threatening cases and for 61% of patients with acute MI in the analysed period of time. Complicated MI was observed in 61.7% of all patients, including 70.5% of men and 49.3% of women. Arrhythmic complications occurred in 54.5% of patients. Ventricular ectopic activity was the most frequent arrhythmia and amounted to 46.6%. The II0 or III0 atrioventricular block occurred in 4.5% of patients. Haemodynamic complications occurred in 12.3% of cases. Sudden cardiac death occurred in 23.6% of patients with acute MI, including 21.9% cases of ventricular fibrillation or flutter and 1.7% of asystole. 28.5% of those patients were successfully resuscitated. 61% of patients died in the prehospital phase of acute MI including 63.4% of males and 57.2% of females. Out of 61% of patients who died before admission to the hospital, 53% had died before ambulance team arrived and 7.9 died being under the care of the ambulance team. 80% of patients who survived prehospital phase of acute MI were admitted to the hospital within 60 min after the call for the ambulance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762281 TI - [First aid at the pre-hospital stage of treatment of acute myocardial infarction]. PMID- 1762282 TI - [The mitral valve in mitral valve defect. Histological and clinical correlations]. AB - The purpose of this study was to investigate the correlation between the histologic changes in the excised mitral valves and the clinical findings in patients with mitral stenosis (with or without regurgitation). The Study group consists of 26 men and 23 women ranged in age from 24 to 56 years. The mitral valves were removed in a uniform manner by one surgeon during mitral valve replacement. The controls were 13 mitral valves removed at necropsy from patients who died of extracardiac causes. Excised valves were fixed in 5% solution of formaline. The extent of calcification was determined by radiographs. Tissue from the center of the anterior and posterior leaflet were selected as the samples. The blocks were paraffin embedded and processed in the conventional manner. For histological examination 11.5 um thick sections were stained with haematoxylin and eosin, Alcian blue, Van Gieson and Von Koss stain. Then the sections were examined under light microscope. We estimated the degree of fibrotic disorganization of architecture, vascularization, acid mucopolysaccharide content, number of fibroblasts, and the presence of calcific deposits and lymphoid infiltrates. The control valves had normal architecture with thick "fibrosa". In all stenotic mitral valves we found complete or partial disorganization of architecture. The most common change was hyalinization present in 94% valves, vascularization in 84% and calcification present in 66% of valves. In 33% of stenotic valves were present infiltrations by lymphocytes. We found a significant correlation (p less than 0.05) between the presence of lymphoid infiltrates and the duration of disease prior to surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762284 TI - [Surgical treatment of patients with Wolff-Parkinson-White syndrome]. PMID- 1762283 TI - [Effects of verapamil and propranolol on the left-ventricular diastolic function in patients with primary arterial hypertension]. AB - Mitral flow was assessed by Doppler echocardiography in patients with systemic hypertension. The study was carried out on 40 patients (27 men and 13 women) aged 24-50 years, mean 43 years with essential hypertension stage II according to WHO classification. No patient had other heart disease or diabetes. All patients were randomly assigned to verapamil (20 patients) or propranolol (20 patients). The daily dose of verapamil was 60-120 mg, mean 80 mg and propranolol 120-180 mg, mean 140 mg. Pulsed Doppler studies in all patients were performed before the treatment and after 4-6 weeks of the treatment. Echocardiographic examination was performed with Hewlett-Packard 707020 A ultrasound system using 2.5 MHz transducer. Two dimensionally guided pulsed Doppler echocardiograms were recorded with sample volume positioned in the inflow area below the mitral annulus. The following Doppler parameters were measured: early diastolic flow velocity (EDF), late diastolic flow velocity (LDF) and their ratio (EDF/LDF) which represents the ratio of early and late diastolic flow velocity of left ventricular filling. The study has showed that before treatment the value of EDF, LDF and EDF/LDF ratio in both groups did not significantly differ. Heart rate and arterial pressure in patients with systemic hypertension after treatment with verapamil or propranolol were significant lower than before treatment. Treatment with verapamil caused significant increase of EDF from 61.2 to 78.2 cm/sek and increase EDF/LDF ratio from 1.02 to 1.30. While LDF values were not changed. In the group of patients treated with propranolol the values of EDF, LDF and ratio EDF/LDF were similar to those before treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762285 TI - Racial differences in the incidence and progression of renal diseases. AB - There is an excess incidence of ESRD treatment among non-White North Americans that is not completely explained by the racial prevalences of the underlying diseases, including hypertension, which can potentially cause renal disease. The racial difference is particularly striking for presumed nephrosclerosis from hypertension and for nephropathy from Type II diabetes, but is not yet substantiated for ESRD attributed to polycystic kidney disease or Type I diabetes. The existing data are insufficient to support the notion that poorer blood pressure control alone is responsible for the racial differences in incident ESRD. Black race (and possibly Mexican or Native American heritage) may be a specific risk factor for ESRD, independent of hypertension and its treatment. PMID- 1762286 TI - Analysis of Na+-D-glucose cotransporter and other renal brush border proteins in human urine. AB - A sensitive quantitative radioimmunoassay is described by which different antigens in the urine can be assayed simultaneously. Urinary excretion of three proteins from proximal tubules was compared: 1) the Na+-D-glucose cotransporter from brush border membranes and subapical vesicles; 2) a kidney-specific hydrophobic M(r) 400,000 polypeptide from intermicrovillar invaginations and subapical vesicles; and 3) villin from microvilli cores. In the normal urine about 50% of the excreted Na+-D-glucose cotransporter and villin, and about 25% of the M(r) 400,000 polypeptide was associated with brush border membrane vesicles, whereas the remaining fractions of the three proteins formed small sedimentable aggregates which contained some cholesterol and fatty acids but no phospholipids. The normal urinary excretion of the Na+-D-glucose cotransporter was correlated with that of villin and the M(r) 400,000 polypeptide. The data show that membrane proteins from the proximal tubule are excreted by the shedding of different brush border membrane areas. They suggest that some microvilli are released in total, and that a large fraction of the brush border membrane proteins is excreted without being associated with a phospholipid bilayer. In an attempt to define protein excretion patterns during kidney malfunctions, the excretion of brush border membrane proteins was analyzed after one intravenous injection of the X-ray contrast medium, iopamidol. No change in villin excretion was observed, but a reversible increase in the excretion of brush border membrane proteins was found in patients without diabetes. With diabetes a more pronounced iopamidol effect on the excretion of brush border membrane proteins and a significant increase in the excretion of villin was observed. PMID- 1762287 TI - Distribution of tubulointerstitial nephritis antigen and evidence for multiple forms. AB - A monoclonal antibody (A8) to a basement membrane component (TIN antigen), which is associated with autoimmune tubulointerstitial nephritis, was developed and utilized to characterize tissue distribution and properties of TIN antigen by immunofluorescence microscopy and immunoblotting. Results were confirmed with polyclonal goat anti-rabbit and human autoantibodies. TIN antigen was found in basement membranes of kidney cortex, small intestines, skin, and cornea, but was not detected in the renal medulla. Within the kidney cortex proximal tubular basement membrane (TBM) showed the strongest staining. TIN antigen was also detected in Bowman's capsule, distal TBM, peritubular capillaries, and focally in the interstitium, but not in glomerular basement membrane or mesangial matrix. Immunoblotting of SDS-extracted human, rabbit, mouse, and Brown Norway rat TBM with A8 revealed predominantly a 58 kD TIN antigen; however, other reactive components were detected in minor quantities. Bovine TBM contained components of 52 kD, 45 kD and 35 kD in varying concentrations. Immunoblotting of isolated rabbit TIN antigen revealed the major 58 kD component that was characterized previously, and minor components of 300 kD, 175 kD, 160 kD and 50 kD. TIN antigen was not detected in Lewis rat TBM by immunofluorescence or immunoblotting. These studies suggest the following: 1) TIN antigen may be synthesized as a high molecular weight glycoprotein that is processed to smaller forms; 2) it may be covalently associated with other basement membrane components; 3) the antibody reactive epitope may be present on multiple TBM components; and 4) high molecular weight forms may represent aggregates of TIN antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762288 TI - Glomeruli synthesize nitrite in active Heymann nephritis; the source is infiltrating macrophages. AB - Glomeruli synthesize nitrite (NO2-) in experimental nephrotoxic nephritis, a model of glomerulonephritis where infiltrating macrophages are pathogenic. NO2- synthesis was studied in active Heymann nephritis (AHN), a model of membranous glomerulonephritis in which macrophages have not been implicated. Active Heymann nephritis (AHN) was induced with purified renal tubular epithelial antigen and adjuvants. Glomeruli isolated at seven to eight weeks after induction (proteinuria 183 +/- 28 mg/24 hr, N = 6; adjuvant controls, 1.2 +/- 0.8 mg/24 hr, N = 6) produced NO2- in culture spontaneously (7.1 +/- 1.4, adjuvant controls 2.1 +/- 0.9 nmol/2000 g/48 hours; P = 0.021) and in increased amount following LPS stimulation (12.1 +/- 2.8, controls 4.2 +/- 1.6 nmol/2000 g/48 hours; P = 0.047). Synthesis was inhibited by L-NMMA, a competitive inhibitor of NO synthase. Enzymic digestion of glomeruli plus staining with mouse anti-rat macrophage monoclonal antibody ED1 showed macrophage infiltration (32 +/- 6, adjuvant controls 14 +/- 2 macrophages/glomerulus; P = 0.002). Whole body irradiation (XR) suppressed NO2- production (LPS stimulated: 1.0 +/- 0.4, N = 5; non-XR controls 7.2 +/- 4.6 nmol/2000 g/48 hours; N = 5, P = 0.016) and macrophage infiltration (1.1 +/- 0.5; non-XR controls 30 +/- 12 macrophages/glomerulus; P = 0.008) but had no effect on proteinuria. Irradiation with renal shielding confirmed the close correlation between glomerular NO2- synthesis and glomerular macrophage numbers (rs = 0.837, P less than 0.001). These results show that macrophages infiltrate glomeruli in AHN; they are the source of NO2- in this model. Neither macrophages nor NO2- are the cause of proteinuria. PMID- 1762289 TI - Renal immunopathology in murine host-versus-graft disease. AB - BALB/c mice neonatally injected with 1 x 10(8) (A/J x BALB/c)F1 hybrid spleen cells develop polyclonal B cell activation and autoimmune features as a consequence of a host-versus-graft (HVG) reaction. In this study, we first analyzed the time-course development of the renal lesions in HVG mice. From week 2 to week 6, linear deposits of IgG were observed by immunofluorescence along the glomerular capillary walls. From week 8 to week 12, the immunofluorescence pattern of IgG changed from linear to granular, and by immunoelectron microscopy, the IgG deposits were located on the epithelial side of the glomerular basement membrane (GBM). In addition, focal glomerulosclerosis complicated this membranous glomerulopathy in about 50% of the 12-week-old HVG mice and albuminuria was increased in most of them. Circulating antibodies to antigens of the GBM (laminin, type IV collagen) and of the renal tubular epithelial (RTE) cells (dipeptidyl peptidase IV, gp330) were already detected at week 2 and were still present at week 12. Immunoglobulins eluted from isolated glomeruli contained antibodies directed against type IV collagen, laminin, and to a lesser degree against gp330. F1 donor B cells were involved in the production of nephritogenic antibodies as indicated by (a) the presence of A/J allotypic determinants on serum anti-laminin antibodies and (b) the abrogation of the in vitro production of anti-GBM, anti-laminin and anti-RTE antibodies when spleen cells from HVG mice were depleted of F1 donor B cells. Finally, mixed lymphocyte culture experiments established that T cells from HVG mice stimulate normal B cells from F1 donor hybrids to produce anti-GBM, anti-laminin, anti-type IV collagen, anti-RTE, anti gp330 and anti-dipeptidyl peptidase IV antibodies. We conclude that mice neonatally injected with semi-allogeneic spleen cells develop a glomerulonephritis characterized by the transition from a linear to a granular IF pattern, and that the production of nephritogenic antibodies results from the activation of donor B cells by host helper T cells. PMID- 1762290 TI - Impaired in vivo antibody production in CRF rats: role of secondary hyperparathyroidism. AB - Antibody responses to antigens are impaired in humans and animals with chronic renal failure (CRF), and parathyroid hormone (PTH) inhibits Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM)-induced antibody production by B cells from normal subjects. Since CRF is associated with secondary hyperparathyroidism and elevated blood levels of PTH, it is possible that impaired humoral immunity in CRF is due to chronic excess of PTH. To test this hypothesis we examined in vivo antibody production in response to sheep red blood cells (SRBC), BSA and influenza vaccine in normal rats, CRF rats and parathyroidectomized CRF rats maintained normocalcemic (CRF-PTX). The blood levels of PTH in CRF rats were elevated and significantly (P less than 0.01) higher than those in normal and CRF PTX rats. The latter groups of animals did not have elevated blood levels of PTH. The antibody response to all three antigens in CRF rats were significantly (P less than 0.01) and markedly lower than in normal or CRF-PTX rats. The antibody response to SRBC, the IgG anti-BSA and the IgG and IgM anti-influenza vaccine in CRF-PTX rats were not different from normal, while the IgM anti-BSA was lower than in normal rats but higher than in CRF rats. The data demonstrate that the state of secondary hyperparathyroidism of CRF plays a paramount role in the genesis of impaired humoral immunity in CRF. PMID- 1762291 TI - Subfractions in uremic plasma ultrafiltrate inhibit calcitriol metabolism. AB - Previous study from our laboratory has demonstrated that uremic plasma ultrafiltrate suppresses both the production rate (PR) and metabolic clearance rate (MCR) of calcitriol in normal rats. To characterize the the substances responsible for the suppression of the synthesis and degradation of calcitriol, we fractionated 20 ml uremic plasma ultrafiltrates into 13 fractions using high performance liquid chromatography (HPLC) and studied the effect of each fraction on calcitriol metabolism. We measured the MCR and PR of calcitriol in normal rats after they were infused for 20 hours with each fraction dissolved in 20 ml normal saline. Using a UV absorption and fluorescence emission technique, several known uremic compounds were identified as individual peaks corresponding to the fractions. We found that fractions 4, and 6 to 13 markedly reduced the MCR of calcitriol. The patterns of the MCR suppression by the HPLC fractions suggest that there were at least two groups of chemically distinguishable compounds. Infusion of a solution containing all 13 fractions of the uremic ultrafiltrate also inhibited the calcitriol synthesis. One of the 13 fractions (fraction 4, containing uric acid, xanthine, and hypoxanthine) was further fractionated into eight subfractions. Infusion of subfractions 4 to 7 markedly reduced both the PR and MCR of calcitriol. We conclude that uremic plasma ultrafiltrate contains factors that inhibit calcitriol synthesis and degradation. These substances have molecular weight less than 2,000 Daltons. PMID- 1762292 TI - Effects of methylprednisolone on glomerular and medullary mRNA levels for extracellular matrices in puromycin aminonucleoside nephrosis. AB - We examined the effects of methylprednisolone (MPSL) on type IV collagen, laminin and heparan sulfate proteoglycan (HSPG) mRNA levels in the renal glomeruli and medulla of puromycin aminonucleoside (PAN) nephrosis. mRNA levels encoding for type IV collagen and laminin increased markedly, whereas those for HSPG decreased significantly in glomeruli of PAN nephrosis. Administration of MPSL partially ameliorated the abnormal gene expression for basement membrane components. Furthermore, we showed that medullary mRNA levels for all these basement membrane components decreased with age in PAN nephrosis with or without MPSL treatment, suggesting that neither PAN nor MPSL has any effect on basement membrane component mRNA levels in the renal medulla. In contrast, mRNA levels for the interstitial collagens including alpha 1 (I) and alpha 1 (III) chains in glomeruli showed little change with or without MPSL treatment, whereas those in medulla increased significantly in PAN nephrosis when compared with the control. MPSL ameliorated the abnormal gene expression of alpha 1 (I) and alpha 1 (III) collagen in renal medulla. These results indicate that PAN affects both glomerular mRNA encoding for basement membrane components and medullary mRNA encoding for interstitial collagens, and that MPSL has marked effects on the amelioration of abnormal gene expression in both glomeruli and medulla of PAN nephrosis. PMID- 1762293 TI - Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide. AB - Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake. PMID- 1762294 TI - Differentially regulated cell surface expression of leukocyte adhesion receptors on neutrophils. AB - To elucidate the molecular mechanisms accounting for hemodialysis-induced neutropenia, the regulation of plasma membrane expression of leukocyte adhesion glycoproteins was investigated by both flow cytometry and immunoprecipitation techniques. The members of the LFA family of integrins, Mac-1/Mo1 (CD11/CD18) and gp150/95 (CD11c/CD18), involved in adhesion of myeloid cells to endothelia and other substrates, were found to be overexpressed on the plasma membrane of neutrophils from patients undergoing hemodialysis with a Cuprophane dialyzer, whereas no change was observed in the expression of LFA-1 (CD11a/CD18). By contrast, dialysis with Cuprophane membranes, as well as in vitro treatment with different activating agents, induced a downregulation on the expression of both the Leu-8/LAM-1 antigen, the human neutrophil peripheral lymph node homing receptor, and the CD43 major sialoglycoprotein involved in leukocyte homotypic adhesion. Kinetics studies showed that these up- and downregulatory processes of antigen expression occur very rapidly, correlating with maximal neutropenia. Recovery of initial levels of expression of CD11b/CD18 and Leu-8/LAM-1 adhesion molecules was observed after one hour of hemodialysis. However, the basal expression of CD43 was not restored by that time. The coordinated upregulation of CD11b and CD11c and downregulation of LAM-1 and CD43 adhesion receptors provide molecular mechanisms for understanding leukoaggregation, adherence to endothelia, and extravasation of neutrophils ultimately leading to the hemodialysis-induced neutropenia. PMID- 1762295 TI - T-lymphocyte subsets in nephrotic syndrome. AB - T-lymphocyte subsets when measured in steroid responsive nephrotic syndrome (SRNS) have demonstrated significant variance from normal values. T-cell subsets were studied by using two-color flow cytometric analysis in 32 children (9.2 +/- 5 years of age) with SRNS. The children were divided into four groups: a) SRNS in acute relapse, on prednisone; b) SRNS in acute relapse, off prednisone; c) SRNS in long-term remission, off prednisone (nephrotic controls); d) patients in remission on long-term prednisone therapy; and e) 15 age-matched normal controls. Children suffering an acute relapse of SRNS showed an increase in Leu2a+/DR+ (CD8) activated lymphocytes (P less than 0.05), a decrease in Leu4a+ total T lymphocytes (P = 0.01) and a decrease in Leu3a+ (CD4) helper T-cells (P less than 0.05) when compared to normal controls and nephrotic controls. Though some subset changes may represent a prednisone effect and the functional role of these lymphocytes in the disease process is unknown, this study provides additional evidence to support a role for abnormal T-cell subsets in the etiology of SRNS. PMID- 1762296 TI - Bone marrow changes following treatment of renal anemia with erythropoietin. AB - In 14 severely anemic patients with end-stage renal disease and chronic hemodialysis the effect of recombinant human erythropoietin (EPO) on hemopoiesis was investigated. Bone marrow biopsies were taken before and after four and 26 months of treatment with EPO to evaluate quantitative and qualitative changes of histomorphology. EPO induced normalization of maturation and an increase in cell mass of the erythropoietic line in all patients. The number of megakaryocyte also increased significantly with EPO treatment (P less than 0.01). At the time of the third bone marrow biopsy (26 months) erythropoiesis was normal. Megakaryopoiesis remained unchanged compared to the second biopsy (4 months). No cytomorphologic abnormalities or other evidence for malignant disorder could be detected in any of the patients. Hematocrit increased from a mean of 19 to 31 percent at the second evaluation (P less than 0.001). Platelet count had risen by a mean of 30,000 at four months (P less than 0.05) and slightly decreased at 26 months. These observations suggest great safety of long-term treatment with recombinant human erythropoietin, and demonstrate efficacy in correcting reduced and immature erythropoiesis in chronically hemodialyzed patients. EPO also stimulates human megakaryopoiesis. PMID- 1762297 TI - Urinary albumin, transferrin and iron excretion in diabetic patients. AB - The present study was undertaken to determine urinary and serum iron, transferrin and albumin levels in diabetic patients with varying amounts of proteinuria. A highly significant correlation was found between urinary albumin and transferrin excretion over a wide range of urinary albumin excretion (0.005 to 18 g/g creatinine) (r = 0.972). The urine/serum ratio of transferrin and albumin were identical, documenting a similar glomerular leak and tubule handling for these two proteins. In contrast to the above correlation between transferrin and albumin, there was no correlation between iron and either of these proteins until nephrotic range proteinuria had occurred, and even at that time the correlation was much weaker than that found between the proteins (r = 0.680). Urinary iron excretion increased early in the course of diabetic renal disease, being increased in 3 of 11 patients without proteinuria and in 8 of 10 patients with mild proteinuria. All patients with nephrotic range proteinuria had markedly increased urinary iron excretion (150 +/- 166 micrograms/g creatinine vs. 6.4 +/- 0.7 micrograms/g creatinine in controls) and decreased serum iron levels (592 +/- 189 micrograms/liter vs. 979 +/- 394 micrograms/liter in the control group). The iron/transferrin ratio in urine was consistently greater than the iron/transferrin ratio in plasma at all stages of proteinuria. In patients with both subnephrotic and nephrotic range proteinuria, approximately 35 to 40 micrograms Fe/g creatinine was present in the urine with an excess of transferrin. In conclusion, urinary iron excretion is increased early in the course of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762298 TI - Prevention of hemodialysis subclavian vein catheter infections by topical povidone-iodine. AB - Subclavian catheter (SCC) related infections are a major cause of morbidity in hemodialysis patients, the vast majority due to staphylococci species. Povidone iodine (PI) has proven anti-staphylococcal activity. Therefore, a randomized controlled trial of topical PI ointment was undertaken to evaluate the impact of this prophylactic intervention on the incidence of SCC related infections in hemodialysis patients. The role of S. aureus nasal carrier state in the acquisition of infection was also evaluated. Patients requiring SCC for temporary hemodialysis access were randomized to receive the treatment (T; N = 63) or sterile gauze dressings alone (C; N = 66). Catheter duration ranged from 2 to 210 days in both groups, with a mean of 38.6 days in T and 36.2 days in C (NS). Exit site (ES) infections were significantly less in T (5%) versus C (18%) (P less than 0.02); tip colonization (TC) was 17% in T versus 36% in C (P less than 0.01), while the incidence of septicemia (S) was also significantly less in T (2%) versus C (17%; P less than 0.01). S. aureus nasal carriers were at a threefold higher risk of SCC related septicemia (0.009/day) than noncarriers (0.003/day; P less than 0.05). The beneficial effect of PI ointment was most evident in this high risk group of S. aureus carriers: ES = 0% T versus 24% C, TC = 12% T versus 42% C, S = 0% T versus 29% C, P less than 0.05. There were no adverse effects of the treatment. The routine application of topical PI ointment to temporary hemodialysis catheter exit sites is effective in reducing SCC related infections. PMID- 1762299 TI - Medical and social outcome in adolescents with end-stage renal failure. AB - Clinical information was collected on 118 adolescents who developed ESRF at age 143 months or older and were treated between 1966 and 1986 at the Toronto Hospital for Sick Children. The cumulative survival rate in transplanted patients (N = 109) was 80.1% after 15 years. Survival rates after four years were 93.9% in transplanted and 46.9% in nontransplanted patients (P less than 0.001). No patient receiving dialysis alone (N = 9) was followed longer than four years. Nine patients received three transplants and had an 89% survival rate. Six of these had a functioning graft at end of the follow-up. The cumulative survival of the entire group was 76.4% at eighteen years. Forty-two (35.6%) patients had a height below the third percentile. Functional status obtained by a structure telephone interview with a member of the present treating nephrology service was good (G) or excellent (E) for 66.7% of all patients (73.5% of transplant patients (N = 68) and 45% of dialysis patients (N = 20). Hemodialysis patients functioned less well [25% G/E (N = 12)] than peritoneal dialysis patients [75% G/E (N = 8)]. Most patients achieved an appropriate level of formal education although more slowly than normal adolescents. Only 11 patients were neither enrolled in an educational institution nor employed. We conclude that aggressive treatment for adolescents with ESRF is an appropriate application of health care resources. PMID- 1762300 TI - Regulation of renal ammoniagenesis in metabolic acidosis. PMID- 1762301 TI - Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy. AB - The possibility that tumor necrosis factor (TNF) and interleukin-1 (IL-1) could participate in the development of diabetic nephropathy was evaluated in streptozocin (STZ)-treated diabetic rats. Diabetic rats were divided into two groups: aminoguanidine treated group (25 mg/kg body wt, daily i.p. injection; DM AG group) and untreated group (DM group). Non-diabetic age-matched rats were also divided into two groups with the same manner and used as controls. After twelve weeks of treatment, glomerular basement membranes (GBM) were isolated from rats of each experimental group. When thioglycollate-elicited peritoneal macrophages (M phi) from normal rats were incubated with these GBM materials, GBM from DM group induced significantly greater levels of TNF and IL-1 production than did GBM from other three groups with at doses of 2.5 to 10 mg. The TNF and IL-1 production by stimulation of GBM from the DM-AG group were similar to those from each control group. Aminoguanidine treatment significantly decreased the accumulation of advanced glycation end-products (AGEs) in GBM of diabetic rats. These findings suggest that AGE-proteins may be involved in the production of TNF and IL-1 from M phi. AGE-induced cytokines may be implicated in the development of diabetic nephropathy. PMID- 1762302 TI - Characterization of myosin heavy and light chains in cultured mesangial cells. AB - Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that postconfluent mesangial cells in primary culture expressed three myosin heavy chains (MHCs), 204 kD, 200 kD and 196 kD, in a manner similar to that of smooth muscle cells. The MHCs of 204 kD and 200 kD in mesangial cells reacted positively with antibodies raised against bovine aorta smooth muscle myosin while the 196 kD MHC reacted positively with antibodies against platelet myosin. Moreover, the combined content of the MHCs in cultured mesangial cells was remarkably similar in amount to that in cultured aortic smooth muscle cells. After three passages, cultured mesangial cells expressed only the 196 kD MHC as has been reported for cultured smooth muscle cells. Two phosphorylated proteins were found in the immunoprecipitate after incubation of the cell extract with antibodies against platelet myosin: a MHC of approximately 200 kD and myosin light chain (MLC) of 20 kD. The level of MLC phosphorylation was quantitated by scanning densitometry of autoradiograms. Arginine vasopressin (AVP) at 100 nM induced MLC phosphorylation with a maximum effect at 10 minutes. AVP enhanced MLC phosphorylation in a dose dependent manner: maximum response was observed with 100 nM and half maximum, at 3.5 nM. Similarly, angiotensin II (100 nM), endothelin-1 (10 nM) and the calcium ionophore, A23187 (1 microM), significantly enhanced MLC phosphorylation. Thus, although the expression of MHC was altered in quality after mesangial cells were placed in culture, the cells remained rich in myosin content and had an intact regulatory system for contraction which responded to a variety of vasoconstrictive agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762303 TI - Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. AB - A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-beta 1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulo-interstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases--stromelysin or collagenase--and a marked increase for TIMP and TGF-beta 1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation. PMID- 1762304 TI - Growth hormone prevents steroid-induced growth depression in health and uremia. AB - Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed. PMID- 1762305 TI - Deterioration of GFR in IgA nephropathy as measured by 51Cr-EDTA clearance. AB - In 191 patients with mesangial IgA nephropathy, GFR was determined as clearance of 51Cr-EDTA. 86 (45%) of them had subnormal renal function 7.3 +/- 4.6 years after renal biopsy. The change in GFR was followed in 153 patients with repeated determinations of 51Cr-EDTA clearance. 50.3% of the patients had a loss of more than 1.1 ml/min/year, which we regard as pathological. The markers of progressive disease were: male sex, high output of urinary protein, severe histological lesions and presence of hypertension. Even patients lacking these markers had a significantly increased incidence of progressive disease. Of 93 patients, with initially normal GFR, 32% will have a subnormal GFR within five years and 25% will develop end-stage renal failure within 20 years. In 38 patients with six or more determinations of 51Cr-EDTA clearance, the predictive value of the first four determinations was calculated. Of 26 with a decrease of more than 1.1 ml/min/year, 13 (50%) developed subnormal GFR during follow-up, while 11 of 12 (91.7%) with a decrease of less than 1.1 ml/min/year (P less than 0.05) remained normal. This shows that repeated determinations of GFR with an accurate method will predict the final outcome early in the disease. We also confirmed that single or repeated determinations of clearance of creatinine are of little value in separating a normal GFR from a slightly decreased one, but more reliable in detecting a markedly reduced GFR. PMID- 1762306 TI - Calcemic response to parathyroid hormone in renal failure: role of phosphorus and its effect on calcitriol. AB - The calcemic response to parathyroid hormone (PTH) is decreased in renal failure. The reduction of hyperphosphatemia improves the calcemic response to PTH in animals with advanced renal failure. However, since low calcitriol levels in renal failure may also contribute to the decreased calcemic response to PTH, the improved calcemic response observed during the reduction of serum phosphorus may be partially mediated by an increase in serum calcitriol levels. The present study evaluated the calcemic response to PTH in rats with moderate and advanced renal failure and how this response was modified by a high and a low phosphorus diet. In addition, the effect of a change in dietary phosphorus on calcitriol levels was also evaluated. A 48-hour continuous infusion of 1-34 rat PTH increased the serum calcium level to 18.2 +/- 0.4 mg/dl in normal rats, versus 13.7 +/- 0.9 and 12.1 +/- 0.2 mg/dl in rats with moderate and advanced renal failure, respectively. During the PTH infusion, a high phosphorus diet increased the serum phosphorus and resulted in a reduced calcemic response to PTH at each level of renal function; respective serum calcium levels were 13.8 +/- 0.6 mg/dl in normals, 11.2 +/- 0.2 mg/dl in moderate renal failure and 9.6 +/- 0.5 mg/dl in advanced renal failure. In normal rats and in rats with moderate renal failure, dietary phosphorus restriction during the PTH infusion increased serum calcitriol levels. In rats with advanced renal failure, serum calcitriol levels were lower than in the other two groups and were not affected by changes in dietary phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762307 TI - Calcemic response to parathyroid hormone in renal failure: role of calcitriol and the effect of parathyroidectomy. AB - Hyperparathyroidism due to renal failure begins in the early stages of renal insufficiency and is in part secondary to skeletal resistance to the calcemic action of parathyroid hormone (PTH). Factors which have been reported to reduce the calcemic response to PTH include: decreased calcitriol levels, hyperphosphatemia and down regulation of PTH receptors in bone. While hyperphosphatemia may directly decrease the calcemic response to PTH, it may also act indirectly by a suppression of calcitriol synthesis. In this study, the effect of calcitriol on the calcemic response to PTH was evaluated in normal rats and in rats with moderate and advanced renal failure. To determine the combined effect of calcitriol and phosphorus on the calcemic response to PTH, rats receiving calcitriol were fed either a high (1.0%) or low (0.2%) phosphorus diet during a 48-hour PTH infusion. In advanced renal failure, calcitriol administration increased the calcemic response to PTH independent of the dietary phosphorus intake. During ingestion of a low phosphorus diet, a 48 hour PTH infusion resulted in a serum calcium level of 13.7 +/- 0.5 and 12.1 +/- 0.2 mg/dl (P less than 0.02) with and without calcitriol administration, respectively. In normal rats and in rats with moderate renal failure, calcitriol administration improved the calcemic response only during a high phosphorus intake. After a 48 hour PTH infusion in normal rats, the serum calcium levels with and without calcitriol were 16.1 +/- 0.9 and 14.8 +/- 0.6 mg/dl, P less than 0.01 respectively; in rats with moderate renal failure, calcitriol administration increased serum calcium, 13.2 +/- 0.5 versus 11.2 +/- 0.4 mg/dl, P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762308 TI - Complement activation retards resolution of acute ischemic renal failure in the rat. AB - We investigated the role of complement activation on the resolution of acute ischemic renal failure in the rat. Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with acute renal failure were exposed to daily zymosan infusion (an activator of the complement system), or to blood incubated with cuprophane (CUP) or polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour proteinuria on Day 3 and Day 5 following ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically. Zymosan and cuprophane exposed rats had a significant delay in the recovery of renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of zymosan-exposed rats to infusion of deferoxamine (DFO), a potent inhibitor of hydroxyl radical formation (OH.). Infusion of DFO prior to zymosan significantly improved recovery of renal function. We also measured urinary thromboxane B2 levels in these groups of rats. While the groups of rats exposed to zymosan had the highest levels of thromboxane B2, these levels were not different between the groups exposed to zymosan alone, or to zymosan and DFO. These observations suggest a role for hydroxyl radicals in the prolongation of renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with acute renal failure. PMID- 1762309 TI - Electrophysiology of ammonia transport in renal straight proximal tubules. AB - To test for electrogenic transport of ammonium ions in straight proximal renal tubules, isolated perfused tubules have been exposed to peritubular ammonium ions during continuous recording of cell membrane potential. As a result, 20 mmol/liter NH4+ leads to a rapid, reversible depolarization of the cell membrane by 9.0 +/- 0.3 mV (N = 86). This depolarization is not significantly affected by 10 mmol/liter barium or 0.1 mmol/liter amiloride on both sides of the epithelium, but is significantly blunted by omission of extracellular bicarbonate and CO2 (3.8 +/- 0.4 mV, N = 9), by 1 mmol/liter acetazolamide (4.3 +/- 0.3 mV, N = 11), by 1 mmol/liter peritubular amiloride (4.3 +/- 1.1 mV, N = 7), by 1 mmol/liter SITS (5.7 +/- 0.4 mV, N = 6), and by replacement of extracellular sodium with choline (4.7 +/- 0.5 mV, N = 8). In the presence of both amiloride (1 mmol/liter) and acetazolamide (1 mmol/liter) in the bath, the NH4+ induced depolarization is completely abolished. Furthermore, the combined omission of bicarbonate and addition of 10 mmol/liter barium eliminates the NH4+ induced depolarization. About 50% of the depolarization can be explained by enhanced electrogenic bicarbonate exit due to the intracellular alkalosis. The other 50% is explained by amiloride and barium sensitive electrogenic entry of NH4+ into the cell. PMID- 1762310 TI - Pregnancy in IgA nephropathy. AB - The impacts of IgA nephropathy and pregnancy on each other were evaluated in 118 women who conceived 168 times between 1970 and 1988. Rates of spontaneous abortion, normal delivery, live birth and perinatal death were 9, 66, 87 and 4%, respectively. Infants born to women with glomerular filtration rates (GFR) lower than 70 ml/min prior to conception had a higher perinatal mortality rate (14% vs. 3%, P less than 0.001). This was also true if pre-pregnancy blood pressures were consistently higher than 140/90 mm Hg (33% vs. 1%, P less than 0.001). These were the figures for the whole 18 year period, but stratification of the data revealed that most adverse results occurred in the 1970's, during which the perinatal death rate was 9%, while it was 0% in the 1980's. Eighty-five women were followed for three years or more. At final follow-up, the rates of decrease in GFR, and increases in blood pressure and proteinuria were 19, 11 and 7%, respectively. In most patients the natural history of IgA nephropathy was similar to that of women who had not experienced pregnancy, but there were five instances where gestation seemed to accelerate functional loss, with rapid development of end-stage or near end-stage renal failure. Most women with IgA nephropathy should anticipate few problems with pregnancy, if they are normotensive and their preconception GFR exceeds 70 ml/min. The gestation in such instances should have little influence on the natural history of their nephropathy. PMID- 1762311 TI - Effects of acetate dialysate on transforming growth factor beta 1, interleukin, and beta 2-microglobulin plasma levels. AB - To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1 alpha, IL-1 beta, IL-6), TNF alpha, TGF beta 1, and beta 2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF beta 1 was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF beta 1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P less than 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P less than 0.10). Acutely, TGF beta 1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70, 52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57, 43 to 69 pg/ml; P less than 0.05). beta 2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM vs. 1.05 mmol +/- 0.07 SEM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762312 TI - Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients. AB - The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile. Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine less than or equal to 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated. Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure greater than or equal to 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 +/- 17; 241 +/- 12 and 211 +/- 11 mumol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration greater than 200 mg/dl and/or plasma triglycerides greater than 172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 +/- 14; 226 +/- 12 and 211 +/- 11 mumol/liter RBC/hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762313 TI - Adherence of neutrophils to hemodialysis membranes: role of complement receptors. AB - Complement activation occurs during hemodialysis using cellulosic dialysis membranes with the consequent deposition of C3 activation and degradation products on the membrane surface. To determine if these complement fragments are functionally active, we examined their capacity to mediate leukocyte adherence to cuprophan membranes. Immunoblotting of proteins eluted from plasma-treated cuprophan membranes confirmed the presence of both C3b and iC3b. Incubation of cuprophan membranes with heparinized whole blood resulted in adherence of leukocytes but not erythrocytes. Neutrophils were the primary cell type bound, with monocytes comprising less than 5% of the adherent cells. Studies using indium-labeled neutrophils demonstrated that the binding was plasma dependent and increased with time up to two hours. Neutrophil binding was inhibited by preincubation of the plasma-treated cuprophan membrane with anti-C3 or preincubation of neutrophils with an antibody directed against the alpha chain of complement receptor type 3 (CR3). These observations indicate that iC3b deposited on cuprophan membrane surface as a result of complement activation mediates neutrophil adherence via interaction with CR3. They also support the hypothesis that, in addition to the anaphylatoxins released into the fluid phase, complement activation products that remained membrane bound during hemodialysis also stimulate pathophysiological responses. PMID- 1762314 TI - Renal functional reserve: its significance in normal and salt depletion conditions. AB - The aim of this study was the evaluation, in healthy subjects, of the renal functional reserve (RFR), that is, the GFR increase induced by a combined infusion of amino acids (AA) and dopamine (D), in conditions of extracellular volume depletion caused by diuretic administration. In particular, this study was undertaken: a) to evaluate whether and to which extent, AA + D can reverse the functional GFR impairment induced by salt depletion, without volume restoration; b) to study whether any relationship may be found between the GFR in normal condition (the so-called "resting" GFR), and/or the renal functional reserve and the GFR impairment induced by salt depletion, in order to understand the role of both "resting" GFR and RFR in the degree of renal dysfunction induced by salt depletion. In control conditions the i.v. infusion of AA + D significantly increased RPF (+ 41% vs. baseline period) with a mean absolute increase of 211 ml/min. A similar pattern was observed in GFR behavior (+31.5% with 34 ml/min of mean absolute increase). A significant inverse exponential relationship was observed between GFR before AA + D i.v. infusion ("resting" GFR) and renal functional reserve (P less than 0.05), suggesting that, in normal conditions, these inversely related parameters may widely vary according to the tone of the glomerular arterioles. Following salt depletion, we observed a variable degree of GFR impairment. Both GFR and RPF were significantly decreased (-25.9%, P less than 0.05 and -29%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762315 TI - Measurement of SC5b-9 in urine in patients with the nephrotic syndrome. AB - In passive or active Heymann nephritis (HN) in the rat, the immune complexes that form in the glomerular subepithelial space result in complement activation and the urinary (U) excretion of S protein-membrane attack complex (SC5b-9, MAC). Because of the similarities between HN in rats and membranous nephropathy (MN) in humans, it has been suggested that measurement of SC5b-9 in urine (UMAC) could be useful in assessing the immunologic activity of MN in patients. The present study was undertaken in normal individuals and in patients with nephrotic syndrome to determine: 1) the conditions of urine collection and preservation needed for accurate measurement of UMAC for clinical purposes; and 2) whether UMAC levels are a sensitive and/or specific test for MN. In studies conducted on urine specimens from patients with increased UMAC levels, we found that UMAC in freshly voided urine was stable for at least three hours at 37 degrees C, with or without the addition of the enzyme inhibitors that were used to stabilize UMAC levels in the studies of HN in the rat. Urine pH, leukocytes and erythrocytes, over the ranges usually encountered, did not influence UMAC levels. However, freezing urine at -70 degrees C artifactually raised UMAC levels (1500 +/- 550 to 1800 +/- 580 SE ng/ml, P less than 0.001 by paired t-test). Normal urine contained low UMAC levels: 80 +/- 3 ng/mg urinary creatinine (UCr). By contrast, patients with glomerulopathies tended to have elevated UMAC levels: 18 of 38 patients had levels that ranged from 200 to 20,000 ng/mg UCr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762316 TI - Anaphylactoid reactions in hemodialysis patients treated with the AN69 dialyzer. AB - During an 11 week period (May to July, 1990), we observed six anaphylactoid reactions (AR) in six different hemodialysis patients occurring at the onset of treatment with a new AN69 hollow-fiber dialyzer. Four patients required cardiopulmonary resuscitation and one of these expired. Four patients were also receiving an angiotensin converting enzyme (ACE) inhibitor while the other two were not on medication known to affect the renin-angiotensin system. Only patients treated with AN69 dialyzers were affected. A review of the literature indicated that out of 1087 patients reported, 72 patients were on the combination of an AN69 dialyzer and ACE inhibitor therapy and 41 (57%) demonstrated AR. Only two patients (0.4%; both from our series) treated with an AN69 dialyzer without ACE inhibitor therapy developed AR. AR did not occur in patients treated with a variety of other dialyzers during this 11 week period, with or without ACE inhibition. Possible causes for AR are discussed and include: (1.) blood-AN69 membrane interaction leading to the production of bradykinin and other vasodilators, the breakdown of which may be delayed by the presence of ACE inhibitors; (2.) hypersensitivity to ethylene oxide; (3.) passage of bacterial products from dialysate to blood; (4.) changes in membrane manufacturing specifications. Recommendations are proposed for the prevention and treatment of AR. PMID- 1762317 TI - Factors predictive of post-transplant erythrocytosis. AB - Ninety-three patients with PTE (that is, hematocrit 51% or greater) were identified among 431 renal transplant recipients, an incidence of 21.6%. Thirty eight patients underwent blood volume measurements, and 22 of these had high red cell volume and therefore were considered to have true PTE. To analyze factors predictive of erythrocytosis, a control group with normal hematocrit was randomly selected from our renal transplant population and compared with the 93 patients with PTE, and with the 22 who had true PTE. Using step-wise logistic regression analysis, we identified three variables that were consistent predictors of PTE. In order of significance, the serum creatinine value at the onset of PTE appears to most strongly predict the occurrence of PTE (P less than 0.0001). As creatinine value increases, the probability of PTE decreases. Next was immunosuppression, where double immunosuppressive therapy was associated with a greater probability of PTE than triple therapy (P less than 0.0001). The overall incidence of PTE in patients on double therapy was 34%, while that for those on triple therapy 10.4%. Last was duration of dialysis for which increasing values correspond to increasing probability of PTE (P = 0.004). Comparison of the serum erythropoietin (EPO) levels for patients and controls yielded a nonsignificant result (P = 0.2507 and P = 0.383 for all patients with PTE and true PTE, respectively), and therefore EPO levels were inappropriately elevated for the level of hematocrit in the PTE group. Only the number of rejections and duration of follow-up (r = -0.3507) were significantly correlated with EPO (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762318 TI - Simultaneous catheter replacement and removal in refractory peritoneal dialysis infections. AB - The present report describes more than nine years of experience with simultaneous removal and replacement of the chronic peritoneal dialysis (PD) catheter in treating refractory mechanical and infectious complications. Simultaneous catheter replacement and removal not only succeeded in 22 of 23 cases with non infectious mechanical complications, allowing uninterrupted PD in all but three, but also succeeded in 30 (83%) of 36 additional cases with persisting or recurring infection. Simultaneous procedures failed in six (17%) of 36 infectious cases, due to persistent infection in two cases and to procedure complications in four cases. The clinical characteristics of the 30 successful infectious cases were compared to the characteristics of both the six failures, as well as 29 additional infectious cases in which the peritoneal catheter was removed but was not replaced because of a variety of serious complications (such as pancreatitis, abscess, sepsis, or fluid overload). At the time of simultaneous catheter replacement in successful cases, temporary control of active peritoneal inflammation was achieved more frequently (80% vs. 31%, P less than 0.001) with a shorter interval of antibiotic coverage (6.4 +/- 0.9 vs. 14.7 +/- 1.3 days, P less than 0.001). In addition, the successful cases were characterized by significantly more Staphylococcal infections (70% vs. 26%, P less than 0.001) and significantly fewer Pseudomonal or fungal infections (6% vs. 59%, P less than 0.001), although successful cases included some non-Pseudomonal, non-enteric gram negative infections (23%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762319 TI - Tumor necrosis factor (TNF alpha) binding protein: interference in immunoassays of TNF alpha. PMID- 1762321 TI - Polycystic kidney disease: clues to pathogenesis. PMID- 1762320 TI - Cimetidine improves the reliability of creatinine as a marker of glomerular filtration. AB - To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with varying degrees of renal dysfunction. After administration of cimetidine for three to six days, serum creatinine level rose in all participants, while CEDTA and CIn remained stable in a subgroup of 14 subjects in whom they were measured before as well as after the administration of cimetidine. The mean (+/- SD) ratios of CCr to CEDTA (N = 39) and of CCr to CIn (N = 19) after ingestion of cimetidine were 1.02 +/- 0.13 and 1.01 +/- 0.13, respectively, and did not differ significantly from unity. This high degree of accuracy of the cimetidine-aided CCr was present over the entire range of renal function in the study population. Our results also indicated an improved precision of the cimetidine-aided measurement of CCr, resulting in a variability that did not differ significantly from that of the measurement of CEDTA or CIn. We conclude that after oral administration of cimetidine, the creatinine clearance can be used as a reliable measure of GFR within a broad range of renal function. PMID- 1762322 TI - Localization and polar distribution of several G-protein subunits along nephron segments. AB - Guanine nucleotide binding proteins (G-proteins) are heterotrimeric proteins involved in signal transduction in epithelia. In addition to possessing a polarized epithelium the nephron is composed of well defined segments, each with distinct receptors, transporters and other functions. Since different G-proteins interact with different receptors, a differential distribution of the various G protein subunits would be expected. To investigate this possibility, polyclonal antipeptide antibodies to several G-protein subunits were used to examine the distribution of these proteins in nephron segments and their localization to apical or basal membrane domains. Immunoblotting of cortical membrane vesicles demonstrated the presence of G-proteins in both the brush border and basolateral membrane. Staining with G alpha common and G alpha s antibodies demonstrated more of these G-protein subunits in the brush border than basolateral membrane. G protein beta subunits were also present in greater quantity in brush border membranes. Immunocytochemical analysis demonstrated good antigenic preservation and basically confirmed the results of immunoblotting of renal cortex. G-proteins were also found to be differentially distributed in the medulla, the amounts increasing with proximity to inner medulla. Only G alpha s and G beta subunits were demonstrated in glomeruli, but all subunits examined were detected in brush borders of proximal and apical membrane of distal tubules in cortex. In outer medulla G alpha s was detected in both basolateral and brush borders of some tubules and only brush borders of others, G alpha i2 and G beta were found in brush border and G alpha i3 was not detected in this area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762323 TI - Partial lecithin:cholesterol acyltransferase (LCAT) deficiency in Balkan endemic nephropathy. AB - The role of lipid abnormalities has been also implicated in the progression of renal diseases. The search for lipid abnormalities in Balkan endemic nephropathy (BEN) has roused sporadic interest and has not been fully elucidated. This study was performed in 54 healthy subjects from the families affected with BEN (group A), 18 members from non-affected families living in the same location (group B), and 25 control subjects (group C). Lipid profiles and lecithin:cholesterol acyltransferase (LCAT) were determined in each subject. The most striking distinction between the groups was that of the LCAT activity, which was abnormally low in group A (39 +/- 2), significantly different (P less than 0.0001) from that of the other groups. Thirty individuals from group A were those accounting for the low LCAT activity (A1). This group had a significantly lower total cholesterol and free cholesterol than all of the other subjects. The entire group A subjects had a significantly lower percentage of free cholesterol than the other two groups. There was no significant difference in HDL cholesterol between any of the groups, but group A1 had significantly higher HDL than group C (P less than 0.04). What emerges from our study is that a certain proportion of subjects from BEN families have a peculiar form of lipid abnormalities associated with an abnormal LCAT activity. At present we have no explanation for these findings. We believe that these changes may have an important role in the pathogenesis of BEN. PMID- 1762324 TI - Selenium deficiency and Balkan endemic nephropathy. AB - Data on selenium (Se) deficiency in Yugoslavia are summarized. These data include the selenium contents of stream sediments, rocks, soils, cereal crops grown in these soils, and human serum and scalp hair from several towns and regions. Analyses of human tissues in Yugoslavia show very low Se concentrations in both endemic and nonendemic areas. In some regions, including those with endemic villages, selenium contents of grains and human serum and hair are extremely low, approaching those in the low-selenium zone in China. According to the biological function of selenium, a very low intake of selenium may be a fundamental underlying condition that would predispose persons to attack by other agents in the development of Balkan endemic nephropathy. PMID- 1762325 TI - Early detection of tubular dysfunction. AB - The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2 microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2 microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1 microglobulin may replace beta 2-microglobulin for screening purposes. The low molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters. PMID- 1762326 TI - Altered urinary beta 2-microglobulin excretion as an index of nephrotoxicity. AB - The experimental and clinical evidence indicate that beta 2-microglobulin (beta 2m) is actively reabsorbed from the glomerular filtrate by receptors on the brush border located in the proximal third of the proximal tubule. Increased beta 2m excretion in the absence of increased filtered load of beta 2m is indicative of nephrotoxicity. The data presented show that urine beta 2m increases and creatinine concentrations decrease within four hours of administration of diatrizoate megalumine (DMG). In 9 of the 20 patients, the urinary excretion of beta 2m (U beta 2m) increased to clearly abnormal values. In 12 of the 20 patients, the beta 2m excretion expressed as mg per g creatinine (Cr), increased from normal (less than 0.30) to an abnormal beta 2m excretion rate. The increased beta 2m excretion per g Cr occurring immediately after DMG administration lead us to conclude that this effect occurs when the nephrotoxic agent is present in the kidney. Based on these data we believe that the onset of abnormal urinary beta 2m excretion coincides with the presence of the causative agent. This criterion therefore, should prove to be useful in determining the time to conduct studies designed to search for the causative agent(s) in Balkan endemic nephropathy. PMID- 1762327 TI - Beta 2-microglobulin in patients with Balkan nephropathy and in healthy members of their families. AB - The aim of this study was to investigate serum levels, urinary excretion and in vitro peripheral blood mononuclear cell (PBMC) production of beta 2-microglobulin in patients with Balkan nephropathy and their families. Increased urinary beta 2 microglobulin excretion was found in Balkan nephropathy, chronic pyelonephritis and glomerulonephritis patients, being highest in the first group. The serum level of beta 2-microglobulin in Balkan nephropathy patients correlated with residual kidney function. Synthesis of beta 2-microglobulin by PBMC, untreated or stimulated by PHA, was not increased in Balkan nephropathy patients or their healthy family members compared to the control group of healthy persons living outside of an endemic region. This study has shown that the increased serum beta 2-microglobulin level in Balkan nephropathy patients is the consequence of the glomerular filtration rate (GFR) reduction. Urinary beta 2-microglobulin excretion was found increased not only in patients but in some healthy members of nephropathic families. beta 2-microglobulin therefore can serve as a marker of the early tubular damage in Balkan nephropathy. However, urinary beta 2 microglobulin is not specific for Balkan nephropathy, lacking specificity required for screening purposes. The different patterns of serum and urinary beta 2-microglobulin, and other urinary proteins, in patients with Balkan nephropathy from patients with chronic pyelonephritis and glomerulonephritis favor the opinion that Balkan nephropathy is a separate clinical entity. PMID- 1762328 TI - Beta 2-microglobulinuria as a predictor of death in a population exposed to Balkan endemic nephropathy. AB - During the year 1974, urinary beta 2-microglobulin (beta 2mu) was measured at monthly intervals using the first-morning urine sample of randomly selected individuals from the BEN affected village of Petka (416 persons) and from the nearby situated control village of Stubica (216 persons). Initial compliance was complete; over 90% of villagers had at least 10 tests performed. beta 2mu, as assessed by radial immunodiffusion (RID), was repeatedly (at least twice) positive in 12% and 1.4% of the populations of the endemic and control villages, respectively. Over the 15 years of follow-up (1974 to 1988), none from the control village developed BEN, while many medical records of the cohort exposed to BEN contained data suggestive of BEN. Death from/with BEN was used as a measure of outcome. Incidence density of 12 was 3.3 per 1000 person/years of observation (19/5723). A single positive beta 2mu test was a sensitive predictor of BEN death (sensitivity = 89.5%). Selecting two or more positive tests as the cut-off point, the specificity and positive predictive value were considerably increased. Using the sulfosalicylic acid test for detection of significant proteinuria, a similar level of validity indices was reached only by four testings. PMID- 1762329 TI - Beta 2-microglobulinuria in a population exposed to Balkan endemic nephropathy: inferences from repeated cross-sectional studies. AB - Baseline data from a study run in 1974, which comprised beta 2-microglobulinuria (beta 2mu) measurements at monthly intervals from 416 members in 112 households from the BEN affected village of Petka, were compared with the results of two subsequent, cross sectional studies. In June 1988, retesting involved 320 available persons from the same households. Another collection of 284 urine specimens took place in October 1989. Prevalence of tubular proteinuria was the same in 1988 and 1989 as it was in 1974, indicating that the level of exposure to nephrotoxic agent did not change over time. Over 94% of the individuals who were always beta 2mu negative in 1974 remained negative in 1988. By contrast, over two thirds (68.7%) of those who were positive two or more times 14 years ago, tested positive upon re-examination in 1988. Particular interest arises from the data on those initially repeatedly positive persons in whom the overt disease did not occur over time; moreover, some appeared to be unaffected in 1988 and 1989 according to our set of laboratory criteria. The results suggest occasional slow progression and even possible reversibility of tubular lesions in individuals living in the BEN affected environment. PMID- 1762330 TI - Beta 2-microglobulin studies in endemic Balkan nephropathy. AB - The diagnosis of BEN and its differentiation from other chronic interstitial nephropathies are difficult because of the insidious onset as well as nonspecific morphological changes in the kidney. Early diagnosis of this disease is by clinical and laboratory findings which have not been universally accepted. This study was designed to determine if the frequency of increased urinary beta 2 microglobulin (U beta 2m) in village populations at risk to develop BEN was significantly higher than that seen in a control population. Individuals in the two population samples were classified in one of three categories: healthy, suspect or diseased. There were 23 individuals who met the criteria for the clinical diagnosis of BEN. Twenty (87%) of these had one or more positive tests for increased U beta 2m. The prevalence of kidney disease in the endemic village population sample was 13.4 times that for the control village population sample. The data show that the healthy individuals living in a village where BEN is endemic have 6.4 times greater chance of having tubular proteinuria than those living in a control area. The coincidence of the finding of U beta 2m in the urine of 87% of those sick with BEN and in 37 of the 342 (10.8%) people judged to be free of kidney disease suggests that a positive U beta 2m test is an early indicator of exposure to a nephrotoxic agent. PMID- 1762331 TI - Environmental renal disease: lead, cadmium and Balkan endemic nephropathy. AB - The similarity of lead and cadmium nephropathy to Balkan endemic nephropathy warrants careful reevaluation of the possibility that these nephrotoxic metals contribute to the production of the endemic renal disease. Low-level environmental exposure may result in a relationship between the concentration of the metals in tissue storage sites and biological fluids that differs from that encountered after occupational exposure. Urine and blood concentrations may therefore be inadequate measures of exposure. Lead is accumulated in the skeleton and cadmium in the liver and kidneys with biological half lives approximating a decade. Non-invasive in vivo x-ray fluorescence or neutron activation analysis can therefore be used to measure cumulative tissue stores. Multiple regression analysis of epidemiologic data could reveal the relative contribution of causal factors, including lead and cadmium, and help to distinguish Balkan endemic nephropathy from other renal diseases using rigorous diagnostic criteria. As long as Balkan endemic nephropathy remains a diagnosis of exclusion, the accuracy of the diagnosis of other renal disease determines the reliability of identification of the endemic disease. PMID- 1762332 TI - A fifteen year cohort based evaluation of beta 2-microglobulin as an early sign of Balkan endemic nephropathy. AB - The occurrence of elevated urinary beta 2-microglobulin (U beta 2m) has been established to be more common in village populations living in areas where BEN is endemic when compared to appropriate control population. In addition, beta 2 microglobulinuria is associated with BEN. It has been demonstrated that there is an increase in the U beta 2m in apparently healthy populations located in high risk areas. It is 15 years since the first systematic investigations of U beta 2m in the villages of Brod Posavina were conducted. The purpose of this study was to determine the value of a positive test for tubular proteinuria as defined by increased U beta 2m, in identifying individuals at risk to develop BEN. In these studies we followed two cohorts for 15 years: one group consisted of individuals who were positive for tubular proteinuria by U beta 2m testing in 1974; the second group was an age and sex matched group from the same village who were never positive after 12 testings in 1974. The results show that a positive test for U beta 2m is associated with 9.9 times greater relative risk of developing BEN when compared to controls that had no positive U beta 2m tests. PMID- 1762333 TI - Relationship of anemia to Balkan endemic nephropathy. AB - Anemia has been reported to be an early sign of Balkan endemic nephropathy (BEN) occurring before the serum creatinine is elevated. This study was designed to determine if anemia occurred more frequently in an otherwise 'healthy' population living in an area where BEN is endemic when compared to a control population. Also, we wished to determine if any relationship existed between anemia and beta 2-microglobulinuria (beta 2mu) in these populations. The prevalence of anemia in the control village population was 7%, compared to 21.4% of the at-risk village population. These data suggest that anemia is a part of the pathophysiologic picture of endemic nephropathy, and that anemia can be found in an early, non azotemic phase of the kidney disease. PMID- 1762334 TI - Anemia in Balkan endemic nephropathy. AB - The severity of anemia in patients at different stages of the evolution of two tubulointerstitial nephropathies, Balkan endemic nephropathy and chronic pyelonephritis, was compared to clarify the previous observations that anemia appears earlier and is more severe in Balkan endemic nephropathy than in other renal diseases. The role of erythropoietin insufficiency as the cause of anemia in endemic nephropathy was studied as well. The severity of anemia increased with the impairment of renal function in endemic nephropathy and was similar to anemia in chronic pyelonephritis. However, in patients with endemic nephropathy at the initial stage of renal insufficiency significantly lower red cell concentrations were found compared with control subjects from the endemic region. In contrast, patients with pyelonephritis did not have decreased red cell concentrations at the early phase of their renal failure, suggesting that earlier appearance of anemia is characteristic for endemic nephropathy. To confirm this finding a study involving larger number of patients would be necessary. The serum erythropoietin levels, inappropriately low for the degree of anemia in patients with renal failure, were unrelated to the type of tubulointerstitial nephropathy. PMID- 1762335 TI - Renal function, protein excretion and pathology of Balkan endemic nephropathy. I. Renal function. AB - Renal function studies were performed on 59 patients who had the clinical criteria for Balkan endemic nephropathy (BEN). They were divided into three groups according to DTPA clearance (DTPA). Group 1, 11 individuals, had a mean age of 41.6 years and DTPA greater than 100 ml/min. Group 2, 20 persons, had a mean age of 49 years and DTPA of 60 to 100 ml/min. Group 3 was made up of 28 people with a DTPA less than 60 ml/min and an average age of 50.4 years. No distinguishing specific or characteristic symptoms of BEN were found in any of the three groups. Anemia was not found to be an early indicator when compared to other forms of progressive renal disease. Proteinuria was minimal and intermittent in all three groups. Maximum concentrating ability was significantly reduced only in the third group. These features do not allow the clinical differentiation of BEN from other chronic progress tubulointerstitial nephropathies. The geographic isolation and familial nature of the disease, associated with minimal proteinuria make BEN a unique entity. Kidney size by ultrasound was decreased in all three groups, suggesting that this may be another early and characteristic feature to BEN. PMID- 1762336 TI - Renal function, protein excretion, and pathology of Balkan endemic nephropathy. II. Protein excretion. AB - The urinary proteins of 40 patients with Balkan endemic nephropathy from the Tuzla region were examined using ultrathin-layer SDS pore-gradient polyacrylamide gel electrophoresis in combination with silver staining. The typical urinary protein spectrum contained immunoglobulin G, Tamm-Horsfall protein, transferrin, albumin, beta 2-microglobulin (beta 2m), immunoglobulin light chains, retinol binding protein, and alpha 1-microglobulin (alpha 1m). Densitometric measurements were used to derive glomerular tubular protein ratios (GTPR) and to characterize protein excretion patterns in the 28 patients who excreted more than 150 mg/liter of protein. Results showed that proteinuria of Balkan nephropathy is predominantly tubular, consisting of low-molecular-weight species. The most commonly identified proteins were alpha 1m, light chains, retinol binding protein, and beta 2m. The pattern of proteinuria based on GTPR did not correlate with the underlying histology or the degree of renal failure. These findings, using the ultrathin-layer SDS pore-gradient method of protein separation, more accurately demonstrates the low-molecular-weight proteinuria characteristic for the early stages of BEN. PMID- 1762337 TI - Renal function, protein excretion, and pathology of Balkan endemic nephropathy. III. Light and electron microscopic studies. AB - This study was performed to evaluate histomorphological features of BEN in 50 kidney biopsies from patients who met the epidemiologic, clinical and laboratory criteria for BEN. This is the first such study reported in detail. The patients were divided into three groups based on the DTPA clearance values: group 1, greater than 99 ml/min, group 2, 51 to 99 ml/min, and group 3, 29 to 50 ml/min. All patients in all groups had an increase in proteinuria consisting of proteins less than 25,000 daltons. Multifocal interstitial sclerosis spreading from the superficial into the deep cortex was found in 49 (98%), tubular atrophy in 48 (96%), and global glomerular sclerosis with microvascular hyalinosis/sclerosis of sclerotic and atrophic changes were significantly increased when compared to age related standards. An accelerated aging process may be assumed to occur in BEN. More peculiar additional findings with much lower incidence and extent included multifocal vascular and glomerular capillary changes resembling the chronic form of thrombotic microangiopathy group of diseases. These findings, together with the presence of arteriolar hyalinosis and tubulointerstitial sclerosis seen in patients with cyclosporine nephrotoxicity suggest that the mechanism of toxicity may be similar to BEN. We conclude that the histopathology is predominantly tubulointerstitial sclerosis without infiltrates. The combination of the histology, tubular proteinuria, geographic distribution, familial occurrence, and the remarkable association with papillary transitional cell carcinoma of the renal pelvis and ureters, qualifies BEN as a unique disease. PMID- 1762338 TI - Renal function, protein excretion, and pathology of Balkan endemic nephropathy. IV. Immunohistology. AB - Few controversial observations on the deposition of immunoglobulins (Igs) and complement components in kidney biopsies of Balkan endemic nephropathy (BEN) patients have been reported. In the present study, direct or indirect immunofluorescence testing of the deposition of IgA, IgG, IgM, C3, C1q, C4 fibrin/fibrinogen, albumin, B2-microglobulin (beta 2m) and Tamm-Horsfall glycoprotein (THG) on frozen renal tissue sections was performed in 52 BEN patients. Glomerular findings were negative or mostly insignificant, with mild or moderate mesangial deposition of IgM in 16, IgA in 11, IgG in three, C3 in 15, C1q in two, C4 in one and fibrin/fibrinogen in two cases, respectively. The predominance of mesangial IgA deposits in five cases suggested IgA glomerulonephritis (GN) concomitant with BEN. Homogeneous lumpy or granular deposits in small extraglomerular vessels contained IgM in nine, C3 in 45, C1q in three, and C4 in one case. Focal linear or granular C3 was noted along the tubular basement membrane in eight cases. Resorptive droplets in tubular epithelial cells contained Igs and albumin, while complement, fibrin/fibrinogen and THG were found in tubular casts. There was no positive reaction with anti beta 2m and anti-THG antibodies. According to these results, humoral immune mechanisms would not appear to play a pathogenetic role in BEN. However, immunohistologic examinations are important in recognition of possible concomitant immune complex-mediated GN. PMID- 1762339 TI - Incidence of tumors of urinary organs in a focus of Balkan endemic nephropathy. AB - A prospective follow-up study which included a 25% sample of the population of Petka, a hyperendemic village located in the vicinity of Belgrade, was conducted over a 15 year period (1974 to 1988). The cohort consisted of 416 members who made up the denominator of 5,723 person-years of observation. Incidence of deaths, either from or with tumors of urinary organs, was taken as a measure of outcome. The diagnosis of tumor was based on pathohistological confirmation. Incidence density of urinary tract tumors was 1.75 per 1,000 person-years. Six individuals had upper urothelial tumors (incidence density = 1.40 per 1000 person years of observation). These tumors occurred in 32% of the cases who had Balkan endemic nephropathy. PMID- 1762340 TI - Balkan endemic nephropathy and papillary transitional cell tumors of the renal pelvis and ureters. AB - Papillary transitional cell tumors of the renal pelvis and ureters occur more frequently in the Balkan countries than in other areas in the world. The populations involved are the same as those who are at risk to develop Balkan endemic nephropathy (BEN). Seventy-seven patients were treated in the Urology Clinic for papillary cell tumors of the renal pelvis and ureters (UTT) from 1986 to 1988. Forty-four of the patients were from areas where BEN is endemic. The at risk population is estimated to be less than 2% of the control population. Eleven of the 77 were on hemodialysis when UTT were detected, and all but one of those were from BEN areas. This finding emphasizes the need for continual monitoring of end-stage renal disease patients for evidence of these tumors. Comparing the frequency of the tumors from our study (1986 to 1988) with that of early studies indicates that the risk of developing the tumors remains very high in the BEN areas. We conclude that the causative agent(s) is still prevalent in the involved areas. PMID- 1762341 TI - Urinary tract tumors and Balkan nephropathy in the South Morava River basin. AB - The aim of this investigation was to study the frequency of urinary tract tumors (UTT) in settlements around the South Morava River and its tributaries where Balkan nephropathy is endemic. For this purpose 659 surgery and autopsy records of patients with UTT were reviewed. The records came from 25 counties and 1279 settlements classified as endemic, hypoendemic and nonendemic. Upper tract urothelial, urinary bladder and kidney tumors were included in the evaluation. A highly significant geographic correlation between Balkan nephropathy and UTT localized in renal pelvis and ureter was noted in the South Morava River valley. These tumors were 57 and 61.8 times more frequent in endemic settlements than in control rural and city populations free of Balkan nephropathy. The frequency of urinary bladder tumors in endemic settlements was also increased compared with the nonendemic villages and large cities, up to 11.9 and 8.5 times, respectively. In endemic settlements, upper urinary tract tumors were five times and tumors of urinary bladder were seven times more frequent in families with Balkan nephropathy than in those without, and up to 224 times more frequent than in the city families. Familial clustering of UTT was also noted. The geographic correlation between Balkan nephropathy and UTT supports the speculation that these disorders share a common etiology. PMID- 1762342 TI - Survey of small molecule and ion binding to beta 2-microglobulin--possible relation to BEN. AB - Using a new method which permits rapid detection of ligand binding to cross linked protein films and crystals, we evaluated a spectrum of ligand binding to cross linked amorphous films of beta 2-microglobulin purified from urine of Balkan endemic nephropathy patients. Among more than 50 substances studied, including amino acids, fatty acids, sugars, nucleotides, nucleosides, and different inorganic ions, only polyvalent cations, such as Cu2+, Ca2+, Zn2+, Be2+ and La3+, were found to strongly bind to human beta 2-microglobulin with dissociation constants in the range 10(-6) to 10(-4) M. These cations can release beta 2-microglobulin from HLA complexes leading to an increased beta 2 microglobulin level in serum. These observations suggest a possible mechanism for the release of beta 2-microglobulin to make it available to exert toxic effects on the kidney as a potential pathogenesis of Balkan endemic nephropathy. PMID- 1762343 TI - Possible pathogenetic role of low-molecular-weight proteins in Balkan nephropathy. AB - Balkan endemic nephropathy (BEN) is a tubulointerstitial disease characterized by increased-low-molecular-weight protein (LMWP), most notably, beta 2-microglobulin (beta 2m) excretion in urine. We previously demonstrated that two species of LMWPs, immunoglobulin light chains (LC) and recombinant alpha interferon (rIF), are toxic at proximal tubule cell membrane level. Myeloma LCs and rIF inhibit Na dependent uptake of 14C-L-alanine and 14C-D-glucose by rat renal brush border membrane (BBM) vesicles at half-maximal inhibitory concentrations, IC50, ranging from 68 to 140 microM for LCs, and 5.4 to 18 nM for rIF. We further demonstrated that LCs bind to high-capacity, low-affinity sites on BBM with dissociation constants (Kd) ranging from 16 to 118 microM, a range similar to IC50s observed with the same LCs. Binding site occupancy is inversely related to alanine (r = 0.95, P less than 0.01), and glucose uptake (r = -0.96, P less than 0.01), implying that LC nephrotoxicity is determined by its binding to BBM. beta 2m shares behavioral and structural similarities with both LC and rIF. Preliminary studies in our laboratory showed that unlabeled LCs compete for the same binding sites on BBM with beta 2m. These observations confirm that all LMWP, including beta 2m, are potentially nephrotoxic. Thus, the characteristic beta 2 microglobulinuria of BEN may be more than a consequence of tubular dysfunction, and may play a pathogenetic role. PMID- 1762344 TI - Relationship between weathered coal deposits and the etiology of Balkan endemic nephropathy. AB - Field studies in epidemiology and environmental geochemistry in areas in Yugoslavia containing villages with a high incidence of Balkan endemic nephropathy (BEN), indicate a possible relationship between the presence of low rank coal deposits and the etiology of BEN. Preliminary results from qualitative chemical analyses of drinking water from shallow farm wells indicate the presence of soluble polar aromatic and polynuclear aromatic hydrocarbons. These compounds may be derived from weathering of low-rank coals occurring in the vicinity of the endemic villages. All of the endemic villages are in alluvial valleys of tributaries to the Danube River. All except one of the clusters of endemic villages are located in the vicinity of known Pliocene age coals. Detailed sampling of the drinking waters and the nearby coals are being undertaken to identify a possible etiologic factor. PMID- 1762346 TI - Spontaneous and induced chromosome aberrations in Balkan endemic nephropathy. AB - The aim of the present study was to investigate the spontaneous aberrations and chromosome breakages induced by X-rays and folic acid deficiency. In patients with Balkan endemic nephropathy (BEN) a higher frequency of spontaneous aberrations and chromosome lesions in medium TC 199 and radiation induced breakages were found compared with the healthy individuals. In BEN patients the 3q25 band was most frequently involved in the aberrations. These results support the idea that 3q25 may play a specific role and be a marker for BEN. Three of the additional five bands with increased frequencies of lesions in BEN patients contain oncogenes: 1q36-c src, 3p25-raf-1, and 6q23-myb. The frequent association of BEN and cancer can be explained by the chromosomal hypothesis of oncogenesis. PMID- 1762345 TI - Erythrocyte delta-aminolevulinate dehydratase measurements in Balkan endemic nephropathy. AB - Balkan endemic nephropathy (BEN) is a chronic progressive kidney disease leading to renal insufficiency. The possible etiological role of some toxic factors was considered in this study by investigating the activity of erythrocyte delta aminolevulinate dehydratase (ALA-D), an enzyme influenced by various environmental factors. We observed that ALA-D activity was markedly decreased in patients with BEN and in 32% of their healthy family members. Glutathione concentration was found normal in all the groups studied, however, it was possible to reactivate the enzyme in vitro by addition of exogenous glutathione. Percent activation was significantly higher in the groups with decreased ALA-D activity. Blood lead levels were within normal range. The results suggest a normal synthesis of ALA-D apoenzyme, and also the presence of some factors, environmental, metabolic, or genetic, which may affect the enzyme activity through binding to the reactive groups in the active center of this enzyme or by oxidation of the reactive groups. Additional studies are necessary to further elucidate the significance of decreased ALA-D activity in BEN and their healthy relatives. PMID- 1762347 TI - [The Nagel anomaloscope in the diagnosis of eye diseases]. AB - The Nagel anomaloscope can be incorporated in the diagnosis of eye diseases. Three parameters are relevant: 1. The measure of the absolute matching range (scale units) 2. The preferred direction of the widened matching range (to red or to green) 3. The luminance matches with the yellow (decreasing matches indicating a pathologic scotopisation). - Six pathologic anomaloscope findings can be differentiated: 1. Pseudoprotanomaly (retinal diseases; type III acquired blue yellow defects) 2. Symmetrically widened absolute matching range (reduced hue discrimination without reference to its etiopathology) 3. Absolute matching range asymmetrically widened to red with scotopisation (retinal diseases; type III acquired blue-yellow defects or type I acquired red-green defects) or without scotopisation (retinal diseases or optic nerve diseases; type III acquired blue yellow defects) 4. Absolute matching range asymmetrically widened to green (mostly optic nerve diseases; type II acquired red-green defects) 5. Acceptance of both end matches ("0" up to "73") with scotopisation (retinal diseases) or without scotopisation (optic nerve diseases) 6. Achromatic matches (selective cone diseases, such as Stargardt's dystrophy or progressive cone dystrophy). Indications for anomaloscope examinations and clinical application of the method are discussed in ten cases. The utility of the Rayleigh-equation consists in diagnosing pathologic scotopisation (differential diagnosis between retinal diseases and optic nerve diseases) and in making a quantitative evaluation of the acquired color vision defect (follow-up examination). PMID- 1762348 TI - [Comprehensive study of the iris in transformed light in simple glaucoma]. AB - Complex examination of the iris under light transformed by various methods - iridochromoscopy with iridochromophotography, transillumination in red light, and fluorescein angiography - was performed on 26 eyes of patients with simple glaucoma and 24 normal eyes of subjects aged between 42 and 76 years. All the methods employed revealed iris changes in 100% of the simple glaucoma cases. The differences found between the study group and the controls were significant (P = 0.01). A highly positive correlation was found between the results of iris fluorescein angiography and iridochromoscopy with iridochromophotography (r = 0.932; P = 0.0005), as well as between the results of iris fluorescein angiography and transillumination in red light (r = 0.921; P = 0.0005). Complex examination of the iris under transformed light showed the most typical changes in simple glaucoma to be exogenous pigmentation of the pupillary and ciliary regions, partial or complete destruction of the pupillary margin, and stromal atrophy affecting the pupil or the entire iris. Defects and thinning of the posterior iris pigment layer, iris vessel permeability disorders associated with hypoperfusion and microneovascularization in the lesser circle and the ciliary region were also found. PMID- 1762349 TI - [Determination of arteriovenous transit time of the choroid with indocyanine green]. AB - We present a very sensitive, yet light-weight videosystem for infrared angiography with Indocyanine green. This system was used to quantify for the first time the choroidal arteriovenous passage time (chAVP) in eight healthy volunteers and eight patients with retinal detachment pre- and postoperatively. The mean normal value of the chAVP was measured to be 3,46 + 0,59 sec. Patients with retinal detachment could be divided into two groups. The chAVP did not change significantly (p = 0,298) from 3,37 + 0,55 sec. to 3,48 + 0,54 sec. in six patients (mean age 49,7 + 5,4 years), who had a simple scleral buckling procedure. In two further patients (63 and 70 years), who had been operated with an encircling band, a postoperative chAVP-delay of 0,72 and 1,48 sec. was detected. This verification of the clinically expected obstruction of choroidal venous outflow after encircling bands emphasizes the validity of the method. Nevertheless, since the procedure is time consuming and detects only marked disturbances, it must be taken as one basic step in the search for the quantification of the choroidal circulation. PMID- 1762350 TI - [Liquid perfluorocarbon in treatment of giant tears]. AB - In 20 cases of giant tears with considerable proliferative changes, vitreoretinal silicone-oil-surgery was performed. With liquid perfluorocarbon, the involuted retina could easily be fixed during the operation in its former position without difficulties, before silicone oil as a permanent tamponade was used. The good results prove that more invasive manipulations, which were formerly necessary, become superfluous using this method. PMID- 1762351 TI - [Automatic perimetry of the central visual field in diseases of the macula]. AB - We developed a program for testing the central 12 degrees of the visual field with a spatial resolution of 1.6 degrees that was easy to operate. The program was designed for the Octopus computer-perimeter and created by means of the SARGON-utility. Our way of examining differed slightly from the standard Octopus procedure. We tested 16 normal eyes and 13 eyes of patients with various diseases of the central retina. Our normal values of differential threshold sensitivities were about 1.8 dB below the normal values of the Octopus system. Sensitivity and specificity of the program were nearly identical irrespective of using our normal values or the Octopus normal values for the calculation of the above mentioned parameters. Sensitivity was 84.6%, specificity 87.5%. The ability of the program to correctly localize retinal defects was shown. The program was designed for follow-up of patients having undergone paramacular lasercoagulation. PMID- 1762352 TI - [Ciliary perfusion pressure in primary open angle glaucoma]. AB - Oculo-oscillodynamography after Ulrich was performed in 103 patients suffering from primary open-angle-glaucoma. More than 67% of these eyes showed an increase of systolic ciliary perfusion pressure, 25% a normal one and only 7% a decreased systolic ciliary perfusion pressure. PMID- 1762353 TI - [Iris fluorescence angiography findings in oculo-oscillodynamography]. AB - Supported by irisfluorescein angiography it should be examined if systolic ciliary pressure found by oculooscillodynamography is to be seen in every part of the uvea. Iris vessels were found to be perfused at 42 mm Hg (Median, Q1-Q3 = 38 45 mm Hg) whereas oculooscillodynamography displayed systolic ciliary pressure to be 69 mm Hg (62-72 mm Hg). This different blood pressure in different districts of the uvea may be one explanation for the particular vulnerability of iris vessels e.g. in ischemic ophthalmopathy. PMID- 1762354 TI - [Monoclonal antibody HMB-45 in diagnosis of intra-ocular melanoma]. AB - 69 eyes, which had to be enucleated because of an uveal melanoma, were investigated immunohistologically. HMB-45-antigen, which is supposed to be highly specific for melanocytic tumours, was found in 68 cases (sensitivity 99%) with a monoclonal antibody. S 100-antigen was positive in 63 cases (sensitivity 91%) using a polyclonal antibody. The addition of HMB-45-immunohistochemistry to routine histological diagnostic procedures is valuable, when a non-melanocytic uveal tumour cannot be ruled out or when the degree of melanoma-invasion has to be determined with greater accuracy. At the site of melanoma-invasion changes of cellular reactivity seem to occur, as 11 of the 69 studied tumours (16%) showed an increased HMB-45-expression in this area. HMB-45-antigen was detectable even in paraffin embedded material obtained from eyes enucleated 30 years ago. PMID- 1762355 TI - [The antiphlogistic effect of the ginkgolide BN 52 021 in the chemically burned rabbit eye]. AB - BN 52 021, a specific antagonist of PAF receptors, was tested in the early-phase treatment of chemically burned eyes in 30 rabbits. The local application of BN 52 021 eyedrops-1% (water-soluble preparation, 5 times daily, in comparison with the other eye as a control) led to a visible anti-inflammatory effect (microscopically and macroscopically) of the chemically burned anterior eye segment. There was only a moderate increase of the concentration of PGF2 alpha after the chemical burn. The use of specific PAF antagonists seems to have a real chance for treatment of inflammatory reactions of the anterior eye segment. A combination with other mediator antagonists should be tested in further experiments. PMID- 1762356 TI - [Silver nitrate burn after Crede's preventive treatment. A roentgen analytic and scanning electron microscopy study]. AB - Following Crede's prophylaxis with silver-nitrate, the cornea of a newborn presented greyish-brown, lime-like plaques on the nasal part of the right eye. A paracentral ulcerating stromal opacification undermined these appositions, when the patient was admitted to the eye-clinic at Aachen. In the material taken in a lamellar keratectomy scanning electron microscopical examination was able to prove the existence of granules, previously described in light-microscopy. These granules measured 100 to 300 nm in diameter and were placed up to 110 microns deep into the corneal stroma of the specimen. An earlier chemical analysis of necrotic material showed no silver specific reaction. By means of EDX-Analysis these granules could be identified as silver-containing. This was once reassured by a newly developed modification of van-Kossa's-staining-method. The fact that the granular deposits contained mainly silver proves that the onset of a sodium chloride-irrigation did not promote an intended therapeutic silver-chloride precipitation and therefore had no effects on the silver-nitrate's penetration abilities. Injuries by silver-nitrate-solutions used for Crede's prophylaxis are seldom but still reported. The mechanism of injury in this case of a child, born by sectio remains unknown. Neither the use of an unusual silvernitrate solution, that was taken from a disposable ampoule (Mova-Nitrat) was reported, nor any corneal injury during sectio mentioned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762357 TI - [Choroid infarct in the posterior pole of the eye]. AB - By means of a choroidal infarct located at the posterior pole current theories concerning the choroidal anatomy are demonstrated. The existence of watershed zones being adjacent in the macular area as postulated by S. S. Hayreh however cannot be confirmed. PMID- 1762358 TI - [Retinopathy as the first symptom of hairy cell leukemia]. AB - Hairy cell leukemia is a seldom non-Hodgkin-lymphoma of the B-cells. The case of a 39 year old male with loss of vision as first sign of hairy cell leukemia is presented. The decrease of vision was caused by intraretinal bleeding into the macula. By means of ophthalmoscopy and angiography we found intraretinal bleedings, soft exudates, microaneurysms and capillary occlusions. The examination of blood cells showed leucocytosis (48.900/microliter), anemia (hemoglobin 8.7 g/l), thrombocytopenia (67.000/microliter) and hairy cells in peripheral blood and in bone marrow. Under treatment with alpha-Interferon visual acuity became normal and the fundus lesions decreased. This case points out that a retinopathy with bleedings and soft exudates can be caused by leukemia which should therefore be excluded by differential blood count. PMID- 1762359 TI - [Iridochromoscopy]. AB - The author has developed methods for examination of the iris in the light of different spectral composition. The studies have revealed that employment of colored filters in biomicroscopy and photography of the iris helps detect the pathologic shifts undetectable by routine examination. Examinations in polychromatic and changing in succession monochromatic light help carry out a sort of spectral analysis of the clinical features of iridal diseases. PMID- 1762360 TI - [Prof. Witold Jan Orlowski 1918-1988]. PMID- 1762361 TI - [Results of experimental studies of the possibility of using low temperature in the treatment of retinopathy of prematurity]. AB - The purpose of the paper was to study whether the use of cryotherapy can cause decrease of angiogenic activity of the primary avascular retina in kittens with oxygen induced retinopathy. The studies showed that after cryotherapy comes to a considerable decrease of angiogenic activity of this part of the retina. It indicates that cryotherapy should arrest the development of more advanced stages of retinopathy of prematurity. PMID- 1762362 TI - [Comparative evaluation of blood flow velocity and pulsation curve in the posterior ciliary arteries supplying the choroid and the anterior part of the optic nerve]. AB - The speed of the blood-flow and the indexes of pulsation in posterior ciliary arteries supplying the choroid and the anterior optic nerve segment were evaluated in 30 healthy persons (60 eyes) aged 20-60 years with intraocular pressure values of 15-20 mm Hg and in 60 persons with primary glaucoma (120 eyes) aged 22-76 years. The investigations were carried out by the method of Doppler focused pulsating ultrasonography, with an 8.0 MHz probe; the instrument used was the TC-2-64 produced by EME (Germany). It was established that the main speed of the blood-flow in the choroid vessels in healthy people is higher than in the arteries supplying the anterior segment of the optic nerve. These speeds are respectively: 15.13 +/- 4.3 cm/s and 12.03 +/- 3.0 cm/s. The difference is statistically significant. The index of pulsation in the posterior ciliary arteries of both vascular systems does not differ in a statistically significant way and amounts respectively: 0.68 +/- 0.13 and 0.71 +/- 0.11. In patients with glaucoma it comes much earlier to a decrease of the speed of the blood-flow and to an increase of the indexes of pulsation together with a raise of the IOP in the system of the choroidal posterior ciliary arteries than in the anterior segment of the visual system. PMID- 1762363 TI - [Value of the ERG in the "pattern" type (PERG) in the diagnosis of glaucoma]. AB - The authors examined 14 persons (20 eyes) aged 51-77 years with open angle glaucoma and 3 persons (5 eyes) aged 37-59 years who were suspected for this condition. The control group consisted of 23 healthy persons (30 eyes) aged 14-40 years. The PERG results were statistically worked up using the t-Student test. Full clinical examinations and PERG were performed by means of the UTAS E-1000 system of LKC (USA) production according to modified by the authors method of May and coworkers. In the observed glaucoma group the authors revealed a statistically significant reduction of the interpeak values of the PERG in comparison with the control group; this points to a lesion of the ganglion cells in the course of this disease. The modified and adapted for the UTAS E-1000 method of May and coworkers and the applied system of conductors ensured the optimal reception of the PERG signals i.e. the maximal amplitude with minimal disturbances. PMID- 1762364 TI - [Behavior of the x wave of the ERG in patients with macular degeneration]. AB - A group of 133 persons (213 eyes) aged 6 to 80 years (mean 37 years) with macula degeneration were analysed. Basic ophthalmological examination and electroretinography were performed. The absent of the x-wave ERG is usually, but not always, connected with worse function of the macula. Pathological ERG and the absent of the x-wave ERG at the same time, suggest unsuccessful prognosis of the disease. PMID- 1762365 TI - [Pathological conditions of the vitreous body in children after eye injuries]. AB - The material consists of 142 eyes in 138 children aged 2-17 years who sustained contusions and perforating injuries. Pathological changes of the vitreous have been observed in 75 p.c. of cases: haemorrhages, opacities, destructive and fibrous changes and even a total fibrosis of the vitreous with shortening of the anatomical axis of the eye. Vitrectomy was performed in 23 cases with extraction of the foreign body in 11. In eyes with a destruction of the vitreous and with vitreoretinal proliferation a laser photocoagulation of the retina or transscleral cryopexy was performed. It is considered that the prophylactical treatment is indicated in all eyes exhibiting structural changes in the vitreous. PMID- 1762366 TI - [Familial exudative vitreoretinopathy--vitreoretinopathia familiaris exsudative. I. Review of the literature]. AB - Presented are the contemporary opinions of the etiopathogenesis, signs, the clinical course as well as the differentiation and therapy of the familial exudative vitreoretinopathy. Attention is called to the variety of the clinical picture of this disease and the importance of fluorescein angiography in diagnosis. PMID- 1762367 TI - [Familial exudative vitreoretinopathy--vitreoretinopathia familiaris exsudativa. II. Report of 4 cases]. AB - The authors present four cases of familial exudative vitreoretinopathy observed in the course of the last years. Our cases appeared sporadically in families and showed a variable picture and clinical course. The accepted differential criterions and difficulties in differentiation are discussed. PMID- 1762368 TI - [Principles of qualifying retinal detachment for pneumoretinopexy]. AB - The gases SF6 and C2F6 were used in 88 patients (88 eyes) with retinal detachment as endotamponade. Eighty eight patients constituted 3 groups in which the gas was used on the basis of following indications: 1) the eyes with retinal detachment from above and with holes between 9-12-3 or with a macular hole; 2) eyes with retinal detachment "without hole" or with a hole for evaluation for its size and localization, as an intervention preceding an extrascleral invagination; 3) eyes with retinal detachment from above in which after extrascleral indentation in spite of a good localization the retina did not reappose. On the basis of the presented material the authors emphasize the values of the pneumoretinopexy as a solitary procedure, a diagnostic procedure or completing an extrascleral indentation. The perils of this method are presented and the causes of failures discussed. PMID- 1762369 TI - [Silicone oil in the surgical treatment of retinal detachment--indications and clinical experience]. AB - Silicone oil is being used with increased frequency for retinal tamponade during vitreous surgery for complicated retinal detachments. Though it is now possible to reattach most detached retinas, the visual outcome of the silicone oil procedure is often disappointing. This is due to the well known complications of silicone oil (i.e. cataract, glaucoma, corneal opacification), and the necessity to remove the silicone oil in a second surgical procedure with a certain risk of redetachment. Possible toxicity to retina and optic nerve has not yet get been completely evaluated. An alternative method is the use of expanding gases for internal retinal tamponade. Expanding gases are not as effective as silicone oil in advanced stages of proliferative vitreoretinopathy (PVR), but are afflicted with much less complications. We reviewed the charts of our patients, operated on for retinal detachment, to analyse the anatomical and functional results with silicone oil versus gas tamponade. Regarding the last 421 consecutive surgical procedures for retinal detachment (368 eyes), silicone oil has been used in 5%, expanding gases in 14%. The silicone oil procedure was restricted to the most advanced cases of PVR. The anatomic success rate with silicone was 72%, with gas tamponade 87%. Visual acuity of 0.05 and better achieved 19% of the eyes treated with silicone oil versus 61% of the eyes with gas tamponade. These results confirm the findings of other investigators: despite of the high anatomic success rate with silicone oil, the functional results are poor. Because many complicated cases of retinal detachment can also be treated successfully with gas tamponade, silicone oil should remain the last step in retinal detachment surgery. PMID- 1762370 TI - [Retinal detachment as a complication of lensectomy in post-traumatic cataract]. AB - Presented were personal observations concerning 76 patients with traumatic cataract who underwent lensectomy. In 12 patients the retina detached in a various postoperative period. Causes and mechanisms of this complication were discussed. PMID- 1762371 TI - [Results of vitrectomy in children]. AB - Presented are the results of vitrectomy in children operated in the Ophthalmological Department of Children Health Centre. The procedure was preformed in 110 eyes including 32 vitrectomies and 78 vitrectomies connected with lensectomy. Operated were eyes with chronical uveitis of various etiology, with posttraumatic changes, after vitreal haemorrhages in Eales' disease, in persistent vitreal artery cases. Improvement of the visual acuity was achieved in 68 cases (61.8 p.c.), deterioration was observed in 28 (25.5 p.c.); the visual acuity did not change in 14 cases (12.7 p.c.). Retinal detachment was the most frequent complication--38 cases (34.5 p.c.); from this number 10 cases (9 p.c.) improved after a repeated operation. PMID- 1762372 TI - [Macular pucker after surgery for retinal detachment]. AB - Twenty four patients with a preoperative macular detachment were subjected to a 6 months observation. The evaluation of the macular function was carried out on the basis of following examinations: the visual acuity, central visual field, dazzling test, Amsler's test and Heidinger phenomenon. The morphology of the changes was evaluated ophthalmoscopically and biomicroscopically by means of Goldmann's lens and the slit-lamp. The macular pucker appeared in 25 p.c. of examined patients, in 16.7 p.c. of cases with non-translucent and in 8.7 p.c. with translucent membranes. In all cases of macular pucker after retinal detachment surgery the macular function remained severely handicapped. PMID- 1762373 TI - [Laser therapy of diabetic changes in the posterior pole of the eye. Early observations]. AB - Presented are the results of treatment of diabetic changes at the posterior pole by argon laser. Among 26 eyes in which the "macular grid" technique was used an improvement or stabilization of vision was attained in 14 eyes, 12 remaining eyes showing deterioration. The anatomical condition improved or it was stabilized in 24 eyes. Focused laser therapy after fluoresceine angiography was used in 15 eyes; improvement or stabilization of the visual acuity was achieved in 12 eyes, deterioration was observed in 3 eyes. The anatomical condition improved or was stabilized in all the 15 eyes. The period of observation amounted 6 months. PMID- 1762374 TI - [Pathogenesis of retinal neovascularization]. AB - Presented are the causes and actual opinions on the pathogenesis of retinal neovascularization. The ischaemic hypothesis of neovascularization is particularly discussed; it is commonly accepted to day as the most probable hypothesis. PMID- 1762375 TI - [Choroid ischemia syndrome]. AB - Presented are the ischemic changes of the choroid on the basis of observation of patients treated in our Department in the course of the last years. In dependence on the advancement of the ischemic changes one can see 3 various types of signs at the fundus. It seems that the most proper name for these changes would be "the choroidal ischaemia syndrome". It is namely a complex of various fundus changes connected by a common pathogenesis but with various kind of causes. PMID- 1762376 TI - [A stereoscopic device for simultaneous imaging of the fundus oculi]. AB - A stereoscopic countershaft worked out by the authors is cooperating with stereoophthalmoscope model 110. The element of the binocular with its original lenses used in the countershaft was supplemented with prisms which rectify the distance of the geometrical centres of the pictures on the frame of a 35 mm film. A vertical central screen prevents the half-pictures to overlap. The length of the optical path beyond the stereoophthalmoscope amounts 130 mm. Simultaneous stereograms of the eye fundus received by means of this construction are characterized by a transversal enlargement 1.3 X, 1.65X and 3.3X. PMID- 1762377 TI - [Medical expert systems and clinical needs]. AB - The rapid expansion of computer-based systems for problem solving or decision making in medicine, the so-called medical expert systems, emphasize the need for reappraisal of their indication and value. Where specialist knowledge is required, in particular where medical decisions are susceptible to error these systems will probably serve as a valuable support. In the near future computer based systems should be able to aid the interpretation of findings of technical investigations and the control of treatment, especially where rapid reactions are necessary despite the need of complex analysis of investigated parameters. In the distant future complete support of diagnostic procedures from the history to final diagnosis is possible. It promises to be particularly attractive for the diagnosis of seldom diseases, for difficult differential diagnoses, and in the decision making in the case of expensive, risky or new diagnostic or therapeutic methods. The physician needs to be aware of certain dangers, ranging from misleading information up to abuse. Patient information depends often on subjective reports and error-prone observations. Although basing on problematic knowledge computer-born decisions may have an imperative effect on medical decision making. Also it must be born in mind that medical decisions should always combine the rational with a consideration of human motives. PMID- 1762378 TI - Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function--the Ulm-Frankfurt Population Study. AB - Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals. PMID- 1762379 TI - Distribution of ischemic cerebrovascular events in cardiac embolism. AB - Distribution and number of ischemic cerebrovascular events were studied in 57 patients who suffered from heart disorders with proven or highly probable source of cardiac embolism and compared to 39 patients with ulcerations of the craniocervical vessels. Patients with coexisting lesions were excluded from the present study. Out of the 57 patients with cardiac disorders, a single episode of cerebral embolism occurred in 33 patients. Of the 24 patients with recurrent ischemic episodes, different vascular territories were involved in only six cases. There was no evidence of a distinct distribution of vascular territories involved in cerebral embolism. The left middle cerebral artery was affected in 42.9%, the right middle cerebral artery in 23.8%, the vertebrobasilar territory in 19%, and the ophthalmic arteries in 14.2%. Statistical analysis revealed no significant differences in lesion localization between the group with a cardiac source of embolism and the group with ulcerations of the craniocervical vessels. There was a high frequency of patients with recurrent cardiogenic emboli in the ophthalmic (6 of 9 patients) as well as in the vertebrobasilar (6 of 12 patients) circulation who experienced a delayed initiation of cardiac assessment. The possibility of cardiac embolism should be considered in any patient with cerebral ischemia, independently of the vascular territory affected. PMID- 1762380 TI - Arterial baroreflex sensitivity and blood pressure variabilities before and after carotid surgery. AB - Carotid surgery is frequently associated with postoperative blood pressure alterations. The role of baroreceptors with regard to these alterations was assessed in 50 patients by determining the pre- and postoperative mechanoreceptor sensitivity after Valsalva maneuver and intravenous injections of angiotensin and nitroglycerine as described by Smyth, Sleight and Pickering. In addition, blood pressure was monitored perioperatively and renin and aldosterone levels were measured. In patients with arterial hypertension a postoperative increase of receptor reactivity can be seen necessitating a reduction of antihypertensive therapy in more than 50% of cases. In normotensive patients no uniform response can be observed. A possible explanation for this effect might be the local increase of pressure in the operated vascular segment. The postoperative reintegration of receptor areas which had been adjusted to a reduced pressure level might induce a more sensitive response than can be seen for the remaining receptors, which usually are less responsive in hypertensive patients. PMID- 1762381 TI - [Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: need for additional growth hormone substitution?]. AB - In a retrospective study of 632 patients with pituitary disease we diagnosed pituitary insufficiency without hypersecretion of any pituitary hormone in 122 patients. Patients were substituted with sex hormones (76%), hydrocortisone (74%) and/or L-thyroxine (77%). 76% had additional growth hormone deficiency, as shown by an increase of growth hormone of less than 5 ng/ml after i.v. administration of L-arginine. In 17% of all patients the diagnosis of osteoporosis was proven or suspected radiologically. 57% had low bone mass of lumbar spine (dualphotonabsorptiometry) and 73% had low bone mass of the proximal forearm (singlephotonabsorptiometry). BMD values of pituitary insufficient patients were in the same range as those of patients with established osteoporosis. More than half of all patients (53%) complained of tiredness, exhaustion and muscle weakness. 40% suffered from adipositas. 77% had hyperlipidemia (68% hypertriglyceridemia and 42% hypercholesterinemia), 18% had hypertension. 14% of the patients had arteriosclerotic events in their history (myocardial infarction or stroke). These figures are higher than incidences shown in the German PROCAM study. These data show an increased prevalence of osteoporosis and vascular diseases. This is in contrast to the general opinion, that patients with pituitary insufficiency are adequately treated by substitution with adrenal, thyroid and sex hormones. Whether other factors such as the additional growth hormone deficiency are responsible for these diseases has to be examined in prospective studies. PMID- 1762382 TI - A need to intensify drug surveillance in Germany. AB - Despite all its limitations, the spontaneous reporting system still forms the basis for drug safety assessments in the Federal Republic of Germany. Although there have been some promising attempts to standardise the methodology of detecting, analysing and evaluating adverse drug events (ADEs) in certain clinico pharmacological institutes and psychiatric departments, the approaches have not been integrated and are used only locally. The only exception is the Freiburg Documentation Centre for Severe Skin Diseases, which is attempting comprehensive, country-wide documentation of toxic epidermal necrolysis (Lyell's syndrome) and Stevens-Johnson syndrome. We show that surveillance of 40% of all hospital beds would allow the acquisition of reliable data even on rare and serious AEs which could then be extrapolated in a statistically meaningful way. The medical societies in Germany have traditionally taken a leading role in establishing standards for the preclinical and clinical investigation of new drug compounds. We suggest that they also make it their task to define the framework for an intensified adverse events monitoring system, since it is the patient who ultimately benefits from a quantification of drug therapy risks. PMID- 1762383 TI - Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity. AB - Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age. PMID- 1762384 TI - [The spontaneous course of compensated autonomous thyroid gland adenomas]. AB - The spontaneous course of 58 patients with compensated autonomous adenoma of the thyroid was followed. Scintigraphic appearance (compensated (CAA) or decompensated (DAA)) was documented and the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating hormone after TSH-stimulating hormone were measured at the beginning of observation and 3.8 years (median) later. During follow-up period, 13 patients (22%) with CAA developed DAA. 9/13 patients (15%) had overt hyperthyroidism with elevated T4 and/or T3 levels, 4/13 patients (7%) had normal thyroid hormone levels. Life table analysis showed a risk for developing hyperthyroidism of 19% at five years. The size of all adenomata measured scintigraphically was increasing during follow-up, and there was no discrimination of CAA from DAA using this technique. Eight CAA patients received iodinated contrast medium but none develop DAA. In conclusion from these results as well as from the literature, there is no indication for surgery or radioiodine therapy of patients with a CAA, even if there are plans to administer iodinated contrast medium. PMID- 1762385 TI - Potassium substitution via the oral route: does its efficacy depend on the anion of the potassium salt? AB - In an open, randomized study, we investigated the effect of oral potassium chloride (KCl) and of potassium citrate/bicarbonate (K-cit/bic) in 42 patients with hypokalemia (less than or equal to 3.5 mmol/l). In both groups 80 mmol K+ were administered daily. The parameters examined were serum potassium concentration, acid-base status, and urinary electrolyte excretion. Parameters were evaluated on days 0, 2, 4, and 6. With KCl, [K+] increased from 3.2 +/- 0.2 (mean +/- SD) on day 0 to 3.8 +/- 0.4 mmol/l on day 2 (p less than 0.005) and 4.0 +/- 0.5 mmol/l on day 4 (p less than 0.005). On day 6 [K+] was also 4.0 +/- 0.4 mmol/l (p less than 0.005 vs day 0). With K-cit/bic, [K+] increased from 3.2 +/- 0.2 to 3.7 +/- 0.4 on day 2, 3.9 +/- 0.5 on day 4, and 4.1 +/- 0.6 mmol/l on day 6 (all p less than 0.005 vs day 0). The increase of [K+] was not different between the two groups. Blood pH on day 0 was in the normal range in both groups and did not change significantly during the study. There was a decrease of carbon dioxide partial pressure (pCO2) with KCl from 38.7 +/- 4.9 on day 0 to 36.4 +/- 3.6 on day 2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762386 TI - Glucose counterregulation in type 1 diabetic patients with decreased symptoms of hypoglycemia after insulin pump treatment. AB - We were interested in studying whether impaired hypoglycemic awareness after intensified insulin treatment with insulin pumps is associated with impaired glucose counterregulation. Glucose counterregulatory hormones were measured in 7 type I diabetic patients with altered symptoms after 6 months of continuous subcutaneous insulin infusion (CSII) (group 1) and in 9 patients with unchanged symptoms of hypoglycemia under CSII (group 2). The groups did not differ in diabetic control, duration of diabetes, or prevalence of neuropathy. Counterregulatory hormone response to an insulin-induced episode of hypoglycemia was measured before (first test) and after 6 months (second test) of CSII. Glucose nadirs and glucose recovery were similar in both groups and both tests. The mean plasma glucagon values demonstrate a lack of glucagon response in both groups and both tests. Growth hormone and cortisol increased in both groups and both tests without any difference between the groups or first and second tests. Epinephrine response was similar in both tests of group 2 (first test: 50 +/- 5 to 416 +/- 73; second test; 45 +/- 5 to 456 pg/ml), while in group 1 the response was not increased significantly in the second test [first test: 32 +/- 6 to 346 +/- 63; second test: 44 +/- 7 to 575 +/- 91 pg/ml; areas under curve (AUC) 11,977 and 16,345 pg x ml-1 x 90 min-1 (p = 0.36)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762387 TI - Campylobacter fetus subspecies fetus infection. AB - During a six-year period five patients with Campylobacter fetus subspecies fetus infections were seen at the Mayo Clinic in Rochester, Minnesota. Bacteremia was observed in two patients, one presenting with aortic valve endocarditis and the other with abdominal atherosclerotic aortic aneurysm. C. fetus subsp. fetus was isolated from tibial tissue of a patient with osteomyelitis. Diarrhea was the main complaint of two further patients, and was also mentioned by the patient with the aortic aneurysm. Despite the use of incubation conditions and selective media geared to detect only Campylobacter jejuni, C. fetus subsp. fetus was isolated from stool specimens of the two patients with gastrointestinal symptoms. The fact that three of five C. fetus subsp. fetus infections observed in this study were associated with intestinal symptoms further supports the importance of the gastrointestinal tract in the pathogenesis of C. fetus subsp. fetus infections. PMID- 1762388 TI - Antithrombin III and early prognosis in polytraumatized patients: a pilot study. PMID- 1762389 TI - [The AIDS nursing concept of the German Federation of Nurses]. PMID- 1762390 TI - [Safety for the care givers]. PMID- 1762391 TI - [Alternative nursing possibilities for patients with AIDS]. PMID- 1762392 TI - [Guidance of coworkers and team development]. PMID- 1762393 TI - [Seeing one's coworkers holistically? Against the uncritical talk about "holistic"]. PMID- 1762394 TI - [Characteristics of the various degrees in the quality of geriatric nursing- group living and group nursing]. PMID- 1762395 TI - [An experiment: group nursing in partner and team work]. PMID- 1762396 TI - [ICN (World Federation of Nurses): guidelines for national nursing societies. The development of standards for education and practice in nursing]. PMID- 1762397 TI - [Relief for the nursing staff by ward secretaries]. PMID- 1762398 TI - [Regulation of costs for supplying inhabitants of old age homes with incontinence aids]. PMID- 1762400 TI - [The patient with artificial respiration in the intensive care unit]. PMID- 1762399 TI - [Equal treatment of part time workers]. PMID- 1762401 TI - [Scoring systems for the early detection of septic complications in intensive care patients]. PMID- 1762402 TI - [Experiences with Seldinger's new central venous catheter]. PMID- 1762403 TI - [Pain therapy with external and implanted pump systems near the spinal cord]. PMID- 1762404 TI - [Postoperative PCA-pain therapy. Wellbeing comes first. Report of experiences from the Stuttgart Katharine's Hospital]. PMID- 1762405 TI - [Realization of hospital hygiene in a large hospital with special regard to the intensive care unit]. PMID- 1762406 TI - [A professional commission "Hygienic Safety of Medical Instruments" of the German Society for Hospital Hygiene has been founded]. PMID- 1762407 TI - [Clinical experiences with use of the Draintec-system for closed rinse-suction drainage]. PMID- 1762408 TI - [Neurologic intensive care units]. PMID- 1762409 TI - [Environmental protection in the hospital]. PMID- 1762411 TI - [Medical refuse and its disposal in gynecological practice]. PMID- 1762410 TI - [Innovative environmental concept for hospitals]. PMID- 1762412 TI - [Use and disposal of cytostatic agents]. PMID- 1762413 TI - [Hospital hygienic legal problems for patient facilities]. PMID- 1762414 TI - [Hygiene in the disposal of infectious refuse]. PMID- 1762415 TI - [When do infusion systems have to be changed?]. PMID- 1762416 TI - [The close relationship between man and his environment. Epidemics and infectious diseases]. PMID- 1762417 TI - [The importance of correct care of dental prostheses in bed patients]. PMID- 1762418 TI - [The effect of antibiotics on the intestinal flora]. PMID- 1762419 TI - [Suicide and attempted suicide: incidence and possibilities of prevention]. PMID- 1762420 TI - [Endoscopy--what hygienic measures are required?]. PMID- 1762421 TI - [Cleaning of endoscopes: manual preparation and endoscope washing machine]. PMID- 1762422 TI - [Ethical limits to our actions]. PMID- 1762423 TI - [Development of stoma care]. PMID- 1762424 TI - Individual responsibility. PMID- 1762425 TI - Smoking prevalence in South Carolina, 1985-1989. PMID- 1762426 TI - Cardiac surgery for patients maintained on chronic hemodialysis. AB - This study confirms and extends the available information about cardiac surgery in patients with chronic renal failure. With appropriate precautions, CABG and valve repair can be carried out in these patients without significant increase in operative mortality or morbidity as compared to patients with normal renal function. However, these patients remain susceptible to accelerated atherosclerosis in native vessels as well as bypass grafts and to complications (thromboembolism, infection) of prosthetic valves. Accordingly, while these patients are often significantly improved as a result of their cardiac surgery, long term outlook is guarded. PMID- 1762427 TI - Regionalized perinatal transport systems: association with changes in location of birth, neonatal transport, and survival of very low birth weight deliveries. AB - Changes in both the location of very low birth weight births and in the number of infants selected for transport were chosen for the evaluation of regionalized perinatal care and its effectiveness in the Lowcountry Perinatal catchment area. The four-year period reviewed was characterized by the initiation of a well defined regionalized perinatal transport program at the Medical University of South Carolina. In conjunction with this increased availability of transport, there was a statistically significant (p less than 0.02) increase in the number of VLBW neonates transported to MUSC after being delivered in community hospitals. This increase was accompanied by an increase in the proportion of infants referred for transport within the first hour of life. Among those neonates referred within the first four hours of life, survival was inversely proportional to the infant's age when the transport team arrived, suggesting that a rapid response by the neonatal transport team was associated with a significantly increased VLBW infant survival. Among all transported infants, in utero continues to be the most efficacious means of transport for VLBW infants and that delivery of VLBW infants at regional medical centers continues to result in the most optimal survival. PMID- 1762428 TI - Before starting resuscitation first know what you are getting into. PMID- 1762429 TI - Smoking cessation and prevention. PMID- 1762430 TI - Fracture prediction for the proximal femur using finite element models: Part I- Linear analysis. AB - Over 90 percent of the more than 250,000 hip fractures that occur annually in the United States are the result of falls from standing height. Despite this, the stresses associated with femoral fracture from a fall have not been investigated previously. Our objectives were to use three-dimensional finite element models of the proximal femur (with geometries and material properties based directly on quantitative computed tomography) to compare predicted stress distributions for one-legged stance and for a fall to the lateral greater trochanter. We also wished to test the correspondence between model predictions and in vitro strain gage data and failure loads for cadaveric femora subjected to these loading conditions. An additional goal was to use the model predictions to compare the sensitivity of several imaging sites in the proximal femur which are used for the in vivo prediction of hip fracture risk. In this first of two parts, linear finite element models of two unpaired human cadaveric femora were generated. In Part II, the models were extended to include nonlinear material properties for the cortical and trabecular bone. While there was poor correspondence between strain gage data and model predictions, there was excellent agreement between the in vitro failure data and the linear model, especially using a von Mises effective strain failure criterion. Both the onset of structural yielding (within 22 and 4 percent) and the load at fracture (within 8 and 5 percent) were predicted accurately for the two femora tested. For the simulation of one-legged stance, the peak stresses occurred in the primary compressive trabeculae of the subcapital region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762431 TI - Fracture prediction for the proximal femur using finite element models: Part II- Nonlinear analysis. AB - In Part I we reported the results of linear finite element models of the proximal femur generated using geometric and constitutive data collected with quantitative computed tomography. These models demonstrated excellent agreement with in vitro studies when used to predict ultimate failure loads. In Part II, we report our extension of those finite element models to include nonlinear behavior of the trabecular and cortical bone. A highly nonlinear material law, originally designed for representing concrete, was used for trabecular bone, while a bilinear material law was used for cortical bone. We found excellent agreement between the model predictions and in vitro fracture data for both the onset of bone yielding and bone fracture. For bone yielding, the model predictions were within 2 percent for a load which simulated one-legged stance and 1 percent for a load which simulated a fall. For bone fracture, the model predictions were within 1 percent and 17 percent, respectively. The models also demonstrated different fracture mechanisms for the two different loading configurations. For one-legged stance, failure within the primary compressive trabeculae at the subcapital region occurred first, leading to load transfer and, ultimately, failure of the surrounding cortical shell. However, for a fall, failure of the cortical and trabecular bone occurred simultaneously within the intertrochanteric region. These results support our previous findings that the strength of the subcapital region is primarily due to trabecular bone whereas the strength of the intertrochanteric region is primarily due to cortical bone. PMID- 1762432 TI - Prediction of femoral impact forces in falls on the hip. AB - A major determinant of the risk of hip fracture in a fall from standing height is the force applied to the femur at impact. This force is determined by the impact velocity of the hip and the effective mass, stiffness, and damping of the body at the moment of contact. We have developed a simple experiment (the pelvis release experiment) to measure the effective stiffness and damping of the body when a step change in force is applied to the lateral aspect of the hip. Results from pelvis release experiments with 14 human subjects suggest that both increased soft tissue thickness over the hip and impacting the ground in a relaxed state can decrease the effective stiffness of the body, and subsequently reduce peak impact forces. Comparison between our fall impact force predictions and in-vitro measures of femoral fracture strength suggest that any fall from standing height producing direct, lateral impact on the greater trochanter can fracture the elderly hip. PMID- 1762433 TI - An experimental method for measuring force on the spinal facet joint: description and application of the method. AB - A technique is described for measuring load magnitude and resultant load contact location in the facet joint in response to applied loads and moments, and the technique applied to the canine lumbar spine motion segment. Due to the cantilever beam geometry of the cranial articular process, facet joint loads result in surface strains on the lateral aspect of the cranial articular process. Strains were quantified by four strain gages cemented to the bony surface of the process. Strain measured at any one gage depended on the loading site on the articular surface of the caudal facet and on the magnitude of the facet load. Determination of facet loads during in vitro motion segment testing required calibration of the strains to known loads of various magnitudes applied to multiple sites on the caudal facet. The technique is described in detail, including placement of the strain gages. There is good repeatability of strains to applied facet loads and the strains appear independent of load distribution area. Error in the technique depends on the location of the applied facet loads, but is only significant in nonphysiologic locations. The technique was validated by two independent methods in axial torsion. Application of the technique to five in vitro canine L2-3 motion segments testing resulted in facet loads (in newtons, N) of 74+ / -23 N (mean + / -STD) in 2 newton-meter, Nm, extension, to unloaded in flexion. Lateral bending resulted in loads in the right facet of 40+ / -32 N for 1 Nm right lateral bending and 54+ / -29 N for 1 Nm left lateral bending. 4 Nm Torsion with and without 100 N axial compression resulted in facet loads of 92+ / -27 N and 69+ / -19 N, respectively. The technique is applicable to dynamic and in vivo studies. PMID- 1762434 TI - Nonlinear dynamic behavior of the human knee joint--Part I: Postmortem frequency domain analyses. AB - Characteristics results of postmortem experiments on five knee-joint specimens are reported. The experiments were performed to investigate the applicability of a local linearization technique that would make it possible to describe the dynamic behavior of the joint in terms of transfer functions. The results indicate that the stiffness of the bracing wires, attached to muscle tendons to create a static equilibrium position, can be accounted for when determining the stiffness of the joint. Besides the static equilibrium configuration, the magnitude of the dynamic load and the type of dynamic load applied to the joint can be shown to have their influence. As the influence of the dynamic load is significant, it has to be concluded that in essence the knee joint has to be regarded as a nonlinear system, making application of a Local Linearization Technique questionable. However, when the magnitude of the dynamic load is included as an additional measurement parameter, an indication can be obtained about the behavior of the joint and the degree of nonlinearity. PMID- 1762435 TI - Nonlinear dynamic behavior of the human knee joint--Part II: Time-domain analyses: effects of structural damage in postmortem experiments. AB - A description is given of the results obtained for step excitation for two human knee joint specimens using a time-domain analysis technique. As was expected from the results of a previous study, the magnitude of the dynamic load applied has a marked influence upon the stiffness and damping values for the two observed vibration modes. Deliberate damaging of selected joint elements also yields a well observable change in the dynamic behavior of the joint although these changes are difficult to interpret. Here the use of a nonlinear dynamic numerical model of the knee joint seems indispensable. An important observation is, however, that the experimental method discussed here enables to quantify the behavior of the joint and therefore may provide a valuable tool for validation of such a model. PMID- 1762436 TI - Application of the u-p finite element method to the study of articular cartilage. AB - The finite element method using the principle of virtual work was applied to the biphasic theory to establish a numerical routine for analyses of articular cartilage behavior. The matrix equations that resulted contained displacements of the solid matrix (mu) and true fluid pressure (p) as the unknown variables at the element nodes. Both small and large strain conditions were considered. The algorithms and computer code for the analysis of two-dimensional plane strain, plane stress, and axially symmetric cases were developed. The u-p finite element numerical procedure demonstrated excellent agreement with available closed-form and numerical solutions for the configurations of confined compression and unconfined compression under small strains, and for confined compression under large strains. The model was also used to examine the behavior of a repaired articular surface. The differences in material properties between the repair tissue and normal cartilage resulted in significant deformation gradients across the repair interface as well as increased fluid efflux from the tissue. PMID- 1762437 TI - Stiffness of canine stifle joint ligaments at relatively high rates of elongation. AB - A falling-weight impact tester was developed specifically to evaluate the tensile characteristics of animal joints at high elongation rates. The tensile force and elongation in the ligaments of the canine stifle joint were measured using a force transducer, a linear variable displacement transducer, and a digital storage oscilloscope. Stiffness and elongation rates were determined at 1 mm and at 2 mm elongation. The stiffness was calculated as the slope of the force elongation curve, and the elongation rate was calculated as the slope of the elongation-time curve. Results demonstrated that stiffness in the canine stifle joints was not affected by the rate of elongation in the 0.1 to 1.0 m/s range. PMID- 1762438 TI - Normal contact of elastic spheres with two elastic layers as a model of joint articulation. AB - An analytical model of two elastic spheres with two elastic layers in normal, frictionless contact is developed which simulates contact of articulating joints, and allows for the calculation of stresses and displacements in the layered region of contact. Using various layer/layer/substrate combinations, the effects of variations in layer and substrate properties are determined in relation to the occurrence of tensile and shear stresses as the source of crack initiation in joint cartilage and bone. Vertical cracking at the cartilage surface and horizontal splitting at the tidemark have been observed in joints with primary osteoarthritis. Deep vertical cracks in the calcified cartilage and underlying bone have been observed in blunt trauma experiments. The current model shows that cartilage stresses for a particular system are a function of the ratio of contact radius to total layer thickness (a/h). Surface tension, which is observed for a/h small, is alleviated as a/h is increased due to increased load, softening and/or thinning of the cartilage layer. Decreases in a/h due to cartilage stiffening lead to increased global compressive stresses and increased incidence of surface tension, consistent with impact-induced surface cracks. Cartilage stresses are not significantly affected by variations in stiffness of the underlying material. Tensile radial strains in the cartilage layer approach one-third of the normal compressive strains, and increase significantly with cartilage softening. For cases where the middle layer stiffness exceeds that of the underlying substrate, tensile stresses occur at the base of the middle layer, consistent with impact induced cracks in the zone of calcified cartilage and subchondral bone. The presence of the superficial tangential zone appears to have little effect on underlying cartilage stresses. PMID- 1762439 TI - Thermographic stress analysis in cortical bone. AB - Under adiabatic (or near adiabatic) conditions a volumetric change in an elastic material will produce a corresponding change in temperature. Based upon this principle, thermographic stress analysis (TSA) measures changes in surface heat flux (which are related to changes in surface temperature) and relates them to a coupled form of strains or stresses. To demonstrate the feasibility of using this technique for biomechanical applications, we thermographically measured heat flux from loaded specimens of cortical bone and correlated the results with strain gage data. Regular parallelepipeds were cut from the cortex of bovine femora and loaded sinusoidally at 20 Hz. At this rate of loading, mechanically induced changes in surface temperature could be sampled (via heat flux) prior to a measureable attenuation of the thermoelastic effect. Correlation coefficients demonstrated a significant linear relationship between TSA and measured and computed mechanical parameters (stress, strain, first strain invariant, and strain energy density). TSA therefore appears to be a promising technology for experimental stress analysis in cortical bone. PMID- 1762440 TI - Thermal property measurements on biological materials at subzero temperatures. AB - The self-heated thermistor technique was used to measure the thermal conductivity and thermal diffusivity of biomaterials at low temperatures. Thermal standards were selected to calibrate the system at temperatures from -10 degrees C to -70 degrees C. The thermal probes were constructed with a convection barrier which eliminates convection inside liquid samples of low viscosity, without affecting the conductivity and diffusivity results. Using this technique, the thermal conductivity and diffusivity of two organ perfusates (HP5 and HP5 + 2M glycerol), one kidney phantom (a low ionic strength gel), as well as rabbit kidney cortex have been measured from -10 degrees C to -70 degrees C. PMID- 1762441 TI - Controlled freezing of nonideal solutions with application to cryosurgical processes. AB - Success of a cryosurgical procedure, i.e., maximal cell destruction, requires that the cooling rate be controlled during the freezing process. Standard cryosurgical devices are not usually designed to perform the required controlled process. In this study, a new cryosurgical device was developed which facilitates the achievement of a specified cooling rate during freezing by accurately controlling the probe temperature variation with time. The new device has been experimentally tested by applying it to an aqueous solution of mashed potatoes. The temperature field in the freezing medium, whose thermal properties are similar to those of biological tissue, was measured. The cryoprobe temperature was controlled according to a desired time varying profile which was assumed to maximize necrosis. The tracking accuracy and the stability of the closed loop control system were investigated. It was found that for most of the time the tracking accuracy was excellent and the error between the measured probe temperature and the desired set point is within +/- 0.4 degrees C. However, noticeable deviations from the set point occurred due to the supercooling phenomenon or due to the instability of the liquid nitrogen boiling regime in the cryoprobe. The experimental results were compared to those obtained by a finite elements program and very good agreement was obtained. The deviation between the two data sets seems to be mainly due to errors in positioning of the thermocouple junctions in the medium. PMID- 1762442 TI - Species dependence of the zero-stress state of aorta: pig versus rat. AB - The zero-stress state of an aorta can be characterized by the angle with which each segment of the vessel opens up when it is cut radially. The opening angle varies with the region of the aorta: significantly with respect to the axial location, less significantly with respect to polar angle of the radial cut. Both pig and rat aortas have large opening angles in the neighborhood of 130 deg in the aortic arch region. In the thoracic region, the species difference is evident. The opening angle of the pig aorta in the middle thoracic region is rather constant in the neighborhood of 60 deg. The opening angle of the rat aorta in the thoracic region varies considerably, decreasing to 10 deg at the lower end of the thoracic region. In the abdominal region the opening angle of the pig increases from 60 to about 80 deg, that of the rat increases from about 10 to 90 deg. The potassium ion has effect on vascular smooth muscle, but has little effect on the opening angle. This suggests that the opening angle is not sensitive to smooth muscle contraction, similar to a previously known result that the opening angle is not affected by papaverine. The vessel wall thickness and vessel diameter were measured. It is shown that the ratio of the wall thickness to diameter of the pig is considerably larger than that of the rat throughout the aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762443 TI - The pressure-flow relation for plasma in whole organ skeletal muscle and its experimental verification. AB - The whole-organ pressure-flow relation in resting rat skeletal muscle is examined for the flow of plasma. Due to the small size of the blood vessels in this organ, inertia and convective forces in the blood are negligible and viscous forces dominate. Direct measurements in the past have shown that skeletal muscle blood vessels are distensible. Theoretical formulations based on these measurements lead to a third order polynomial model for the pressure-flow relation. The purpose of the current study is to examine this relation experimentally in an isolated muscle organ. A high precision feedback controlled pump is used to perfuse artificial plasma into the vasodilated rat gracilis muscle. The results indicate that the pressure-flow curve in this tissue is nonlinear in the low flow region and almost linear at physiological flow rates, following closely the third order polynomial function. Vessel fixation with glutaraldehyde causes the curves to become linear at all pressures, indicating that vessel distention is the primary mechanism causing the nonlinearity. Furthermore, the resistance of the post-fixed tissue is determined by the pressure at which the fixative is perfused. At fixation pressures below 10 mmHg, the resistance is three times higher than in vessels fixed at normal physiological pressures. Dextran (229,000 Dalton) is used to obtain Newtonian perfusates at different viscosities. The pressure-flow relation is found to be linearly dependent on viscosity for all flow rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762444 TI - The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: an in vitro model study. AB - A steady flow, in vitro model of distal arterial bypass graft junctions was used to examine the effects of junction angle and flow rate on the local velocity field. Three test sections were fabricated from Plexiglas tubing having anastomotic junction angles of either 30, 45, or 60 deg. Flow visualization revealed velocity profiles skewed toward the outer wall with a flow split around a clear stagnation point along the outer wall. Laser Doppler anemometry [LDA] measurements confirmed a distinct stagnation point at the outer wall and both reverse and forward shear were detected immediately upstream and downstream, respectively, of this site. Axial velocities and shear rates along the outer wall were higher than along the inner wall and occurred in the junction angle order: 45, 60, and 30 deg. This study clearly identified changes in wall shear which varied with the anastomotic angle and flow rate. PMID- 1762445 TI - Pulsatile non-Newtonian flow characteristics in a three-dimensional human carotid bifurcation model. AB - Numerical analysis of flow phenomena and wall shear stresses in the human carotid artery bifurcation has been carried out using a three-dimensional geometrical model. The primary aim of this study is the detailed discussion of non-Newtonian flow velocity and wall shear stress during the pulse cycle. A comparison of non Newtonian and Newtonian results is also presented. The applied non-Newtonian behavior of blood is based on measured dynamic viscosity. In the foreground of discussion are the flow characteristics in the carotid sinus. The investigation shows complex flow patterns especially in the carotid sinus where flow separation occurs at the outer wall throughout the systolic deceleration phase. The changing sign of the velocity near the outer sinus wall results in oscillating shear stress during the pulse cycle. At the outer wall of the sinus at maximum diameter level the shear stress ranges from -1.92 N/m2 to 1.22 N/m2 with a time-averaged value of 0.04 N/m2. At the inner wall of the sinus at maximum diameter level the shear stress range is from 1.16 N/m2 to 4.18 N/m2 with a mean of 1.97 N/m2. The comparison of non-Newtonian and Newtonian results indicates unchanged flow phenomena and rather minor differences in the basic flow characteristics. PMID- 1762446 TI - One-dimensional computer analysis of oscillatory flow in rigid tubes. AB - The dynamic characteristics of catheter-transducer systems using rigid tubes with compliance lumped in the transducer and oscillatory flow of fluid in rigid tubes were analyzed. A digital computer model based on one dimensional laminar oscillatory flow was developed and verified by exact solution of the Navier Stokes Equation. Experimental results indicated that the damping ratio and resistance is much higher at higher frequencies of oscillation than predicted by the one dimensional model. An empirical correction factor was developed and incorporated into the computer model to correct the model to the experimental data. Amplitude of oscillation was found to have no effect on damping ratio so it was concluded that the increased damping ratio and resistance at higher frequencies was not due to turbulence but to two dimensional flow effects. Graphs and equations were developed to calculate damping ratio and undamped natural frequency of a catheter-transducer system from system parameters. Graphs and equations were also developed to calculate resistance and inertance for oscillatory flow in rigid tubes from system parameters and frequency of oscillation. PMID- 1762447 TI - Sedimentation of a suspension in a centrifugal field. AB - To model centrifugal sedimentation of biological suspensions, the time history of sedimentation of particles in a centrifugal field was considered for two geometries: a tube and a cylindrical container. The Kynch theory for batch gravitational settling in Cartesian coordinates based on mass conservation was extended to include a centrifugal sedimentation force, cylindrical coordinates, and the Hawksley-Vand hindered settling model. The resulting quasi-linear partial differential equation was solved by the method of characteristics. The combination of radial dependence of the sedimentation force and cylindrical geometry in the centrifugal case results in several differences in the time position history diagram of the sedimentation process compared to the gravitational case. First, instead of a region of uniform concentration equal to the initial concentration, a region of concentration that is continuously decreasing with time results. Second, in the region of particle accumulation, curved constant concentration contours result instead of straight lines. Finally, a secondary shock that is dependent upon the initial concentration and the radius ratio of the rotating vessel appears in the centrifugal case. The time history of the concentration for a particle suspension with an initial concentration typical of blood is presented. PMID- 1762448 TI - Cardiac mechanics at the cellular level. AB - The active mechanical properties of heart muscle are load, length, and time dependent. The capability for investigating cardiac mechanisms at the cellular level may help to distinguish between those properties of the myocardium which arise from myocardial cells and those which arise from the tissue architecture and extracellular matrix of connective fibers. We present here, for the first time, a general approach for subjecting single heart cells to isometric, isotonic, afterloaded, or physiological loading sequences, while obtaining on line measures of cell force and length. This approach has been implemented and tested on freshly dissociated, adult frog ventricular myocytes. Examples are presented for each of the four loading sequences. PMID- 1762449 TI - Comparison of vascular perfusion in ischemia-sensitive and ischemia-resistant regions of gerbil brain by an automated laser cytometric device: a preliminary study. AB - Reduced blood supply in the hippocampus has been considered to be a factor contributory to this region's selective susceptibility to ischemia. To determine if there are differences in vascularization of vulnerable and resistant regions of the brain, a quantitative morphometric assessment of vascular filling was performed in the gerbil brain by using a relatively new and highly sensitive automated laser cytometric device, ACAS (Adherent Cell Analysis and Sorting). Evan's blue, an intravital vascular tracer, was injected intracardiac in 5 Mongolian gerbils to identify perfused blood vessels in the cortex and CA1 region of hippocampus. Exactly 3 min later, the animal was decapitated, the brain removed and sections prepared for fluorescent quantitative morphometric analysis of blood vessels. The perfused vessels appeared as fluorescent structures due to the autofluorescent property of Evan's blue. Several fields in each of the two specified regions were studied and integrated numbers of blood vessels/mm2 obtained for statistical comparisons. Control brains perfused with normal saline (vehicle for Evan's blue) were used to determine the background fluorescence. The number of perfused blood vessels of all sizes was found to be lower in the CA1 sector of hippocampus than that in the cerebral cortex. The number of capillary size vessels was also lower in the CA1 region but the difference was not significant. Since it is the capillaries that are of prime importance in the diffusion system, and we found no significant regional difference in the density of capillary size vessels, it appears unlikely that the peculiarities of patterns of vascularization contribute significantly to vulnerability to ischemia. PMID- 1762450 TI - Threshold depolarization measurements in resting human motoneurones. AB - Threshold depolarization is defined as the amplitude of the depolarization that will just bring a neurone to its firing threshold. Here, a novel technique is described for the measurement of threshold depolarization in resting human motoneurones. The tibial nerve was stimulated at an intensity that was just sufficient for the resulting Ia afferent volley to activate a single motor unit in the soleus muscle. The same motor unit was then recruited by voluntary activation, and the amplitude of the EPSP elicited by this stimulus was determined by a manner described earlier. The value found for the threshold depolarization was around 5 mV for all 6 motoneurones that were successfully tested. PMID- 1762451 TI - Adrenal medullary "ribbon" grafts in non-human primates: transplant method. AB - A novel stereotaxic method permits the transplantation of autologous adrenal medullary tissue into the brain parenchyma in longtailed macaques. Long, narrow "ribbons" of intact medullary tissue are drawn into a 19 gauge needle by suction and deposited in the caudate, putamen or substantia nigra without collapsing their linear conformation. Methods of dissection, preparation of medullary ribbons, stereotaxic insertion, and chronic intracerebroventricular treatment are described in detail. The ribbon method consistently yields a large amount of viable adrenal tissue after the 4-8 week survival times tested. Although further development is necessary before this method can be applied in humans, the results suggest that autologous adrenal tissue may be viable when transplanted in human parkinsonian patients according to these methods. PMID- 1762452 TI - A simple computer-controlled analogue ramp generator for producing multiple ramp and-hold stimuli. AB - This report describes an inexpensive ramp generator which produces multiple ramp and-hold stimuli ("staircase-type" wave forms). The output voltage is analogue and is, therefore, free of stepping artifacts characteristic of digital function generators. When coupled with a standard power amplifier and mechanical vibrator, this system is particularly suitable for stimulation of mechanoreceptive sense organs. Connection to the serial port of an IBM personal computer, or the user port of a BBC computer allows complex ramp-and-hold sequences to be developed and repeated. The number, duration and sign of ramps, and the duration of intervening hold periods can be set using the computer. This system has been used successfully to characterise phasic and tonic neurones in the locust metathoracic femoral chordotonal organ (a leg position and movement detector). PMID- 1762453 TI - Kainic acid lesions of the superior olivary complex: a horseradish peroxidase study of surviving brain-stem projections. AB - Lesions of the superior olivary complex of the adult ferret were made by pressure injection of kainic acid (5 nM/microliters in Locke's solution) through a glass micropipette inserted into the lower brain-stem. Small injections of kainic acid (1.5 microliters) produced a localized loss of nerve cells in the superior olivary complex in the vicinity of the pipette tip without apparent damage to fibers of passage in the trapezoid body. The extent of neural damage was determined by the absence of cell bodies in Nissl-stained sections. Integrity of fibers in the trapezoid body and other decussating pathways of the auditory lower brain-stem was confirmed by retrograde transport of horseradish peroxidase (HRP) following large injections of the enzyme into the central nucleus of the inferior colliculus. Even animals with complete destruction of the superior olivary complex had a normal complement of HRP-labelled cells in all divisions of the cochlear nucleus (the dorsal, anteroventral and posteroventral nuclei) contralateral to the HRP injection. In cases with partial lesions, normal labelling was also seen in those parts of the superior olivary complex not directly destroyed by the kainic acid injection. There was no evidence of disruption of fibers of passage nor was there any indication of abnormal projections from the lower brain-stem to inferior colliculus even after prolonged survival times. PMID- 1762454 TI - The effects of number of trials per day, retention interval, gender and time of day on acquisition of a two-choice, win-stay water-escape working memory task in the rat. AB - A 2 x 2 x 2 factorial study was conducted to examine the effects of gender, trials/day (TPD), and retention interval (RI) on acquisition of a two-choice win stay water-escape task in 4-month-old Sprague-Dawley rats. Variations of this task have previously been shown to be sensitive to changes in working memory that occur with age (Means and Kennard, 1991) or to follow treatment with an anxiolytic (Bass et al., 1989) or with cognitive enhancers (Comer and Moore, in press) in males or to estrogen in ovariectomized females (O'Neal et al., 1990). Both training with 1 TPD and with a 5-min RI, time between an information "run" and a test "run", reduced errors during acquisition as compared to giving 3 TPD and a 1-min RI (P less than 0.05 in all cases). Males made fewer errors than did females (P less than 0.05). The three effects were additive: males trained with 1 TPD and a 5-min RI performed best and females trained with 3 TPD and a 1-min RI performed worst. Also, rats given 1 TPD made fewer acquisition errors when trained 2 h before the lights were turned off than when trained during the middle of the light portion of the light/dark cycle (P less than 0.05). Finally, when given 3 TPD, the rats, especially the females, performed significantly worse on their third trial (P less than 0.05). It was concluded that two-choice win-stay water-escape is a very sensitive assay of working memory with much potential for neurobehavioral research. PMID- 1762455 TI - Methods for studying the conductance changes associated with synaptic activation of forebrain slices: the interpretation of field potentials using CSD profiles. AB - In this report the cortical slice preparation and an array electrode that instantaneously records laminar field potentials are used to evaluate issues related to the interpretation of cortical CSD profiles. The major issues are: (1) what cell types are responsible for producing the source/sink pairs seen in CSD profiles; (2) what neurotransmitters are responsible for producing the sinks/sources seen in the CSD profile and do the sinks/sources reflect activation of receptors that produce inward currents, outward currents, or both; (3) can active and passive currents be distinguished; (4) do action potentials contribute to the CSD profile; and (5) can synaptic population with different kinetics and onset latencies be distinguished? Methods for analyzing neuronal circuits and analyzing CSDs quantitatively are discussed. PMID- 1762456 TI - [Cerebral abscess in a general hospital. Analysis of 66 consecutive cases]. AB - BACKGROUND: Analysis of the epidemiologic characteristics of cerebral abscesses and comparison with 2 therapeutic schedules. METHODS: The clinical history of 66 patients with cerebral abscesses admitted over 14 years in the Neurosurgical Ward of the Virgen de la Arrixaca Hospital in Murcia were reviewed. Two therapeutic groups were designed of 33 and 31 patients respectively treated with classical or modern schedules and clinical efficacy was evaluated. RESULTS: Infections in the ORL area, craneoencephalic trauma, and brain surgery were the predisposing factors in 63% of the cases. The most frequent symptoms were migraine, fever, and alteration of consciousness in 75, 68 and 68% respectively. The most frequent locations were the temporal (36%), parietal (26%) and frontal lobes (23%). Microbiological studies were positive in 75% of the patients with the most frequent microorganisms being group A Streptococcus, Proteus mirabilis, Staphylococcus aureus and anaerobes. Mortality was 14%. Twenty-two percent of the patients had neurological sequelae. The rate of mortality was significantly associated to age greater than 40 years, fatal underlying disease, coma, initial clinical criteria and inadequate antibiotic treatment. The combination of cephotaxime-metronidazole was significantly associated to greater cure in comparison with the classical antibiotic combination although no significant differences were found in either the rate of mortality or relapse. CONCLUSIONS: The combination of cephotaxime-metronidazole may constitute an interesting advance in the treatment of these processes. The epidemiological data obtained confirm those of larger series. PMID- 1762457 TI - [Glycemic control and lipoprotein profile in type I diabetes mellitus]. AB - BACKGROUND: To analyze the relation between the degree of glycemic control and the lipoprotein profile in type I diabetes mellitus. METHODS: Seventy-five diabetics were studied in whom the total glycohemoglobin (GHb), total triglycerides (TG), triglycerides of very low density lipoproteins (TG-VLDL), total cholesterol (TC), cholesterol of very low density lipoproteins (C-VLDL), cholesterol of high density lipoproteins (c-HDL), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) were determined. Patients were classified according to their GHb: less than 9% (good glycemic control), 9-11% (moderate glycemic control) and greater than 11% (bad glycemic control). There was homogeneity in the 3 groups with regards to other variables which influenced the lipoprotein profile. RESULTS: The concentrations of TG, TG-VLDL, TC, C-VLDL and C-LDL were significantly higher in the groups of greater GHb while those of C-HDL, Apo I and Apo B were independent of the degree of glycemic control. The number of patients whose lipid profiles may be considered as atherogenic risk increases progressively in groups with greater GHb. CONCLUSIONS: In patients with type I diabetes mellitus, bad glycemic control is accompanied by decreases in TG, TC and C-LDL up to a magnitude which frequently reaches risk values for developing vascular disease. However, in these subjects, a less protector effect dependent on C-HDL is not to be expected since their concentrations are similar to those patients with good glycemic control. PMID- 1762458 TI - [Nutritional status in uremic patients treated with continuous ambulatory peritoneal dialysis. Relation with 1 year's evolution]. AB - BACKGROUND: Signs of malnutrition have been detected in patients with chronic renal failure and a possible relation with complications of the disease has been speculated. The aim of the present study was to analyze the nutritional status of a group of patients with the aforementioned diagnosis on a substitutive treatment program with outpatient continuous peritoneal dialysis (CAPD) and its relation with complications over one year. METHODS: The nutritional status of 29 of these patients and 22 individuals with normal renal function (controls) with global parameters of body fat, muscular protein and visceral protein being evaluated. The study was repeated at 6 and 12 months after the initial evaluation. The incidence of mortality, need for hospital admission because of complication and episodes of clinical peritonitis were analyzed. RESULTS: More than 70% of the patients presented protein-caloric malnutrition to a greater or lesser degree. This percentage dit not modify throughout the study and was produced at the expense of visceral protein, additionally affecting the fat and muscular protein of the males. Mortality, need for admission and the number of cases of peritonitis were greater in those presenting the lowest fat parameters with these complications beings foreseen from determined fat values. CONCLUSIONS: These patients have malnutrition which is related with the complications in the course of substitutive therapy making surveillance and nutritional support necessary. PMID- 1762459 TI - [Carbohydrates and lipids: metabolically related]. PMID- 1762460 TI - [Brain abscess]. PMID- 1762461 TI - [Thalassemia minor with iron overload: genetic and clinical study of a family]. AB - A patient with thalassemia minor (TM) is reported who ingested 80 g of alcohol/day and presented an important overload of iron with deposits and a hepatic iron ratio compatible with primary hemochromatosis. The results obtained from the study of histocompatibility antigens, clinical manifestations and family analysis discarded the possibility of two genetic diseases, beta-thalassemia and primary hemochromatosis, being concomitantly present in the same progeny. Thalassemia minor and alcoholic hepatopathy are considered as having acted together and being responsible for the iron overload. The relation between alcohol ingested, TM and iron deposits is discussed. PMID- 1762462 TI - [Treatment of pneumonia associated with mechanical ventilation]. PMID- 1762463 TI - [Diagnosis of solid masses in native kidneys with acquired cystic renal disease]. PMID- 1762464 TI - [Myopathy caused by fenofibrate]. PMID- 1762465 TI - [Acute psychosis after the administration of a single doses of intravenous biperiden]. PMID- 1762466 TI - [Rifampicin and doxycycline in the treatment of brucellosis]. PMID- 1762467 TI - [Meningitis caused by Clostridium cadaveris]. PMID- 1762468 TI - PC-based research-oriented clinical information system: a case study of Kuwait. AB - This paper describes the design and application of a clinical information system (CIS) in a tertiary care facility (Kuwait Center for Cancer Control) using low cost microcomputers (personal computers). The facility focuses on the collection and use of clinical information for prospective application in clinical trials, individual therapy and research. In order to meet this requirement the patient treatment and follow-up system (PTFS) was developed, based on recent database management technology. The exercise demonstrates that low-cost microcomputer systems can be used effectively in meeting the clinical management information and research needs of care facilities. It is anticipated that the application of the system will be replicated on other health care facilities. PMID- 1762469 TI - Incorporating user and dialogue models into the interface design of an intelligent patient monitor. AB - A user and dialogue modelling approach is proposed for the development of user interfaces for intelligent patient monitoring systems. Illustrative models and dialogues are developed and simple examples of user interfaces for a monitor system based upon these are presented. The user model and dialogue method is also used to evaluate some interface techniques from the literature. PMID- 1762470 TI - Interactive statistical analysis system for clinical investigators. AB - We have developed an interactive statistical analysis system (ISAS-Q) with which clinical investigators with little experience in computers and programming can easily perform statistical analyses. ISAS-Q can perform most of the frequently used statistical methods, including multivariate analysis, in an interactive mode. Furthermore, ISAS-Q has self-consistent and extensive help functions. PMID- 1762471 TI - A computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention. AB - In this paper a computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention is presented. Cost-effectiveness analysis makes it possible to compare the cost-effectiveness of different interventions in order to maximize the health effects for a given amount of resources. The computer simulation model was written in Turbo-Pascal to be used on an IBM-PC-compatible. The model was based on the 8-year logistic multivariate risk equations for CHD and stroke from the Framingham Heart Study, but the regression coefficients can easily be changed if local data exist. The main advantages with the model are that it is easy to use, transparent, and flexible. The model was mainly developed for scientific purposes, but should be useful also for educational purposes and clinical decision analysis. The modelling approach used should also be useful in many other medical areas. PMID- 1762472 TI - The effect of incomplete knowledge on the diagnoses of a computer consultant system. AB - The knowledge bases (KBs) of diagnostic decision support systems are often incomplete, and gaps in the KB could potentially lead systems to reach diagnoses that are implausible to physicians. To investigate this possibility we studied Iliad (Version 2.01), a computer consultant system that generates differential diagnosis across the domain of internal medicine. Data from the history, physical examination, and laboratory findings of 50 grand-rounds cases were entered into Iliad by a computer consultant aware of the diagnosis but blinded to its presence or absence in Iliad's KB. Two experienced internists were asked to diagnose these cases before and after seeing the results of the computer consultation, and to assess the plausibility of the computer's diagnoses. Twenty-eight of the 50 cases (56.0%) were diseases contained in Iliad's KB. After seeing Iliad's diagnoses for cases in the KB, physicians assigned to their correct diagnoses a higher mean ranked position (1.5 versus 2.0, p less than 0.008) and a higher mean probability (84.0% versus 77.6%, p less than 0.008) compared with their pre-Iliad values, whereas for cases not in the KB, mean position and probability for correct diagnoses did not change. Physician diagnostic accuracy did not change after consultation on cases included or not included in the KB. After adjusting for case difficulty, mean plausibility of Iliad's diagnoses was judged significantly higher (on a seven-point scale) for cases in the KB than for cases not in the KB (4.2 versus 3.2, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762473 TI - Data security in medical information systems: technical aspects of a proposed legislation. AB - This paper analyses the results of a recent survey performed among medical establishment personnel in Greece, evaluates information security legislation existing in other countries and incorporates guidelines of international societies to propose principles governing a future legal framework. Furthermore, it presents a design methodology for designing secure information systems and provides an example of the use of this methodology in designing a database oriented secure medical information system with access rights incorporated. PMID- 1762474 TI - Current status of medicinal research in helminth diseases. PMID- 1762475 TI - Computer-assisted drug design. Part I. Conditions in the 1980s. PMID- 1762476 TI - [Chronology of civilian suffering in the war against Croatia]. PMID- 1762477 TI - [The civilian massacre in Dalj on 1 August 1991]. AB - On August the 1st, 1991, Yugoslav Federal Army and Serbian terrorists attacked the village of Dalj, near Osijek in Eastern Slavonia. The civilians took refuge in Osijek and Hungary, but many of them were captured by terrorists. Their fate is still unknown, and the number of missing persons is more than 300. The Federal Army denies the entry to the village and permitted only 25 cadavers to be taken to the Osijek Hospital. Two out of 25 were civilians: P. D., a baker of Albanian origin, and N. T., baker's assistant, a Croat. The decedent N. T. was killed from the back by rifle fire, while the decedent P. D. was first beaten and then executed by two close-range gunshots in the head. PMID- 1762478 TI - [Civilian massacre in Banija: Kraljevcani and Pecki, 14-16 March 1991]. AB - On 14 and 16 August 1991, Serbian terrorists attacked two villages near Petrinja in the Banija region. The village of Kraljevcani was attacked on 14 August, when the terrorists killed five older villagers, 3 women and 2 men who stayed in the village to watch the livestock and the houses. The women were killed by automatic rifle fire and grenades, and the bodies of the two men were blown up by a hand rocket-launcher projectiles. On 16 August 1991, Serbian terrorists captured four villagers from Pecki, who came to the deserted village to feed the livestock left after the inhabitants fled from the terrorists. The forensic medical expertise revealed that they were first wounded by rifle fire, then tortured and finally executed by hand axes and bayonets. PMID- 1762479 TI - [Civilian massacre near Podravska Slatina, 3 September 1991]. AB - Twenty one civilians, 5 women and 16 men, were found dead in their doorways and yards after Serbian terrorists attacked the village of Cetekovac on 3 September 1991. The age of the decedents ranged from 18 to 91 years. The oldest victims were women (aged 63, 68, 72, 86 and 91). The wounds found on 19 decedents were characteristic of the long-range gunshot wounds, with projectiles fired mostly from the back or/and the side of the body. The autopsy of one decedent (J. B.) revealed that he died from two stabbing wounds and that those were the only wounds inflicted to the body. The body of the decedent (M. S.) was heavily carbonized so that the cause of the death or even whether he was alive when his body was set on fire could not be estimated. PMID- 1762480 TI - [Destruction of the General Hospital in Osijek by the Federal Army (13-17 September 1991)]. AB - The article provides documentation on destroyment of General Hospital of Osijek in the period from September 13th until September 17th 1991. By heavy artillery of the Federal army, primarily from garrison "M. Stanivukovic" the Hospital was shut 94 times and unnumbered times by bullets from light weapons. Most of the hospital Wards are destroyed and for a time being General Hospital Osijek works mostly in the shelters and other underground facilities. Intensity of the assault on the Hospital shows that, in spite of many humanitarian war regulations, it was a primary target for Federal army artillery. PMID- 1762481 TI - [War injuries in Sisak in 1991]. AB - A review of 465 persons wounded during the war in Sisak, Croatia, is presented. The nature of injuries are listed as follows: 337 persons were wounded by fire arms, 120 by beating or falling, 4 by knife, 3 by low temperature and 1 person was injured by high temperature. Of 465 injured patients 7 were dead at the time of admission to the hospital and the other 6 died within one hour of arrival. Special surgical care was necessary for 17 persons and it was provided in Zagreb. Of particular interest was the treatment of the large skin defects caused by high velocity small missiles. The authors emphasize the importance of accurate and adequate stage-treatment which begins immediately on the battleline and proceeds in the ambulance and hospital. PMID- 1762482 TI - [War injuries in children]. AB - The pathology of the wartime injuries in children, the ways of injuring, primary and secondary surgical treatment, and principles of war surgery applied in children age are analysed. Some typical patients admitted to the Clinical Hospital for Pediatric Surgery of the Institute for Mother and Child Health in Zagreb are presented. PMID- 1762483 TI - [War injuries of the thorax]. AB - Chest injuries are very common in war circumstances. Chest injury is commonly associated with other injuries of intrathoracic organs and development of shock, which has to be treated immediately. Our patients with war chest injuries are presented, along with our approach to the treatment of these injuries. "The conservative treatment" is stressed, with particularly importance of proper chest drainage, as a corner stone of proper and successful therapy. Shock treatment and prevention of atelectasis does present an unavoidable procedure of this type of therapy. PMID- 1762484 TI - [War injuries of the blood vessels]. AB - In this article the authors review their personal experience with shotgun injuries to the blood vessels. To date literature demonstrates a significant difference between the military injuries to the blood vessels versus the peacetime ones in the terms of healing. Injuries from high velocity missiles as well as blast injuries produce a massive damage of the tissue, muscles, bones, nerves and blood vessels. Therefore, such injuries demand a careful and appropriate primary surgical treatment and urgent revascularization within the ischemic tolerance of the tissue. PMID- 1762485 TI - [Injuries of the urogenital system]. AB - War injuries of the urogenital system present serious injuries accompanied with significant morbidity and mortality as well as causing high degree of later disablement. The paper presents our experiences and basic directions in treating urogenital injuries especially those penetrating and inflicted by high velocity missiles. Thirteen patients with urogenital injuries have been operated on and that makes 4% of all war injuries treated at KBC-Rebro hospital. Among the total number of abdominal injuries those urological make a considerable share--as high as 21% and that could be the consequence of the triage. In all the patients except one, in whom either kidney, ureter or bladder has been injured there has also been an associated injury of another abdominal organ (mostly colon and small intestine, than liver and spleen). All the operating procedures have been performed together with the general surgery team. X-ray preoperative examinations have been carried out only in two patients while the general state of the rest of the patients has not allowed for such procedures which could delay surgery. Nephrectomy has been performed in only one out of these thirteen patients. Orchidectomy has been carried out in only one patient in whom extensive laceration of the testis has occurred, while in others preserving surgical treatment has been applied. PMID- 1762486 TI - [Infections in war injuries]. AB - Between April and September 1991, 415 injured patients were treated at the University Hospital Rebro, Zagreb, 362 at the Department of Surgery and 53 at the Department of Neurosurgery. Infections developed in 15.7% of the injured patients (wound infections in 14.6% and sepsis or meningitis in 1.1% of the injured patients). 88.2% of wound infections as well as all sepsis and meningitis were hospital-acquired infections, while 7.95 of wound infections occurred within 48 h of injuring. The major pathogens, in 90% of cases, were the aerobic bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter species) while 9% of infections were caused by mixed aerobic-anaerobic flora. One injured patient developed clinical features of gas gangrene. Neither streptococcal wound infections nor tetanus were present in this group of the injured patients. PMID- 1762487 TI - [Advantages of arthroscopy in a military setting]. AB - The military setting does not leave room for the diagnostic evaluation of intra articular injuries and long-term postoperative rehabilitation. In this sense, diagnostic and surgical arthroscopy has an irreplaceable value. The authors present six patients, members of the Ministry of the Interior and the National Guard, with the knee injuries sustained under battle conditions who were treated successfully with diagnostic and surgical arthroscopy. With arthroscopic equipment, already owned by many orthopedic and trauma institutions in Croatia, arthroscopy (diagnostic and surgical) is safe and cost effective procedure, what is a further advantage of this method, both in peace- and in wartime. PMID- 1762488 TI - [War injuries of the extremities. Use of the CMC fixator]. AB - The injuries of the extremities in the military setting, during hostilities, are classified to be the most frequent in general. Among them there are those caused by the missiles from rifles and automatic and semiautomatic weapons and those due to mine and shell fragments. The characteristics of modern array of weapons are missiles of high kinetic energy provoking extensive tissue injuries, often together with fractures of the long bones. When taking care of such fractures, in addition to surgical treatment of the wounds, the administration of medicine and prevention, the immobilization of the fragments is of fundamental significance. All modern armies in the world use external fixators for the immobilization of the fragments, those fixators being the most reliable and the most uncomplicated means of immobilization. The paper presents a new type of the external fixator to be used in war surgery. It is called the CMC fixator (Croatian Medical Corps). The fixator is made according to the original designs in the factory (Instrumentarija) at Zagreb. Following its biomechanic characteristics the fixator is classified into the group of unilateral or joining external fixators. It is designed for fixation of the long bone fractures in the war setting and disaster conditions. It may be used for two purposes: 1. for the transport immobilization to a medical facility where the problem is to be finally solved, 2. as the means of an external immobilization until the final secondary bone healing. The fixator has only three elements and the universal kee. It is easily applied. The way how to apply this fixator is described in details. The first experiences in the field have given satisfactory results. PMID- 1762489 TI - [Transfusion therapy in the war setting]. PMID- 1762490 TI - [Anesthesiology problems in the treatment of the wounded]. PMID- 1762491 TI - [Intensive therapy of the wounded at the Department of Anesthesiology and Intensive Therapy in the Surgery Clinic in Rebro]. PMID- 1762492 TI - [Chemical warfare agents]. AB - In this article a chemical weapons are reviewed. Most important groups and some of the agents are presented as well as the mechanism of their action, symptoms and therapy. PMID- 1762493 TI - [Views on war injuries of the locomotor system]. PMID- 1762494 TI - [Rules for extending first aid for wounded with and without bone fractures]. PMID- 1762495 TI - [Drainage of the thorax]. PMID- 1762496 TI - [First aid in maxillofacial injuries]. PMID- 1762497 TI - [Psychiatric disorders in war and other catastrophic circumstances-- posttraumatic stress disorder]. AB - The paper presents mental disorders occurring in people as a consequence of facing extraordinary situations of mental stress which surpass common human experience and are very frequent in war circumstances. Since 1980 all similar conditions have been classified as a single entity called Post-Traumatic Stress Disorder (PTSD). The disorder may occur immediately after the traumatic experience (acute form), or several months and even years later (chronic, delayed form). The etiology and therapy of the PTSD is discussed. PMID- 1762498 TI - [Care of children during wartime]. AB - Children represent the most vulnerable segment of the civilian population during wartime. Besides the direct effects of weapons and destructions during warfare, children are particularly prone to other forms of damage; extensive disruptions in the environment of the individual child are setting the stage for an increased appearance of infectious diseases, and long term limitations of adequate nutrition are causing various forms of malnutrition and of nutritional deficiencies. The consecutive decrease of general resistance against infectious diseases is an important dispositional factor in the pathogenesis of recurrent and chronic infections. Most severe, far reaching and often irreversible damages are those of mental health of children, sometimes lasting for the whole lifetime of the individual. Some of the most simple but effective preventive measures to alleviate the suffering of children during wartime, accessible to every health worker are briefly reviewed. PMID- 1762499 TI - [Health care of the aged in the war setting]. PMID- 1762500 TI - [Stress erosions and ulcers]. AB - The modern concept of the etiopathogenesis of stress erosions and ulcers is given in this paper. The importance of prophylaxis is emphasized due to the very complex problems of treating wounded in situation where medical institutions are being intentionally damaged and where delayed evacuation is a common occurrence. PMID- 1762501 TI - [Problems and recommendations for the care of refugees displaced by war in Croatia]. AB - The present situation in Croatia and the principles of displaced person camp organization are described. Displaced person care has become the urgent problem imposed on the Croatian social service and health care system. The up to now work has revealed that their is a need for more precise categorization of displaced persons in order that a comprehensive registration system be developed. The number of registered displaced persons in Croatia up to 26 September 1991 is quoted. Based on problems noted in the organization of displaced person camps, elements of organization and known principles of health care system in Croatia, a new model of displaced person camp organization is proposed. PMID- 1762502 TI - [Work at the Department of Psychiatry and Psychology at the Medical Headquarters of the Republic of Croatia]. AB - During the summer 1991, the Ward of Psychiatry and Psychology at the Medical Headquarters, Republic of Croatia has been established as a direct reaction to the cruel war in Croatia. The aim of the Ward is to prevent mental disorders among the individuals participating in the war and among the population of Croatia. Special attention is given to the threatened groups. These are: injured patients, displaced persons, children who have lost one or both of its parents, members of families of persons who have been killed or injured and the others. Treatment doctrines have been provided as well. Besides, a regional psychiatric service which has been formed in accordance with the characteristics of this war which is carried out without a known front, mobile psychiatric groups have also been established. They are made up of volunteers. Particular attention has been directed toward the education and publishing. The first Croatian war psychiatry entitled "Introduction into the War Psychiatry" is going to be published very soon. A program of the so-called veterans hospital has been worked out as well. PMID- 1762503 TI - [Drugs used in war conditions]. PMID- 1762504 TI - [Possibilities of pharmaceutical production under war conditions]. PMID- 1762505 TI - [Drugs for the physician's bag]. PMID- 1762506 TI - [Management of pain in injured patients]. PMID- 1762507 TI - [Topical treatment of war injuries]. PMID- 1762508 TI - [Prevention of wound infection]. PMID- 1762509 TI - [Prevention of wound infection in craniocerebral war injuries]. PMID- 1762510 TI - [Yugoslavia: oppression of physicians in Kosovo]. PMID- 1762511 TI - [Letter from Croatia]. PMID- 1762512 TI - ApoA-I secretion by rabbit intestinal mucosa cell cultures. AB - Lipid and apolipoprotein (apo) A-I concentrations in different density fractions of New Zealand White (NZW) and Watanabe (WHHL) rabbit plasma were studied. Aside from the low plasma apoA-I and high density lipoprotein (HDL) cholesterol levels in WHHL rabbits, the distribution of apoA-I was also different between the two rabbits. ApoA-I was concentrated in both the HDL2 and HDL3 fractions of NZW rabbits but was found primarily in the HDL3 fraction of WHHL rabbits. ApoA-I secretion in these two rabbits was further studied in vitro by using intestinal and hepatocyte cell cultures. ApoA-I secretion was highest from cultures of the duodenum and the proximal end of the jejunum; whereas, cell cultures of the distal end of the small intestine secreted very little apoA-I into the medium. Intestinal cell cultures from WHHL rabbits secreted less, but significant amounts of, apoA-I compared to that of NZW rabbits. ApoA-I was most concentrated in the density range of 1.12-1.21 (HDL3) fraction in medium containing 10% fetal calf serum (FCS). Serum-free medium promoted apoA-I secretion by intestinal cell cultures that was mostly found in the d greater than 1.21 (lipoprotein-deficient) fraction. Hepatocytes isolated from the same rabbits by collagenase perfusion secreted little apoA-I, and it was found only in the d greater than 1.21 fraction. The addition of oleic acid into the culture medium with 10% FCS decreased the secretion of total apoA-I and HDL by intestinal cell cultures and increased the secretion of very low density lipoprotein (VLDL) and intermediate density lipoproteins (IDL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762513 TI - Decrease in platelet reduced glutathione increases lipoxygenase activity and decreases vitamin E. AB - Unstimulated normal human blood platelets were treated with azodicarboxylic acid bis(dimethylamide) (diamide), a thiol-oxidizing agent. Oxygenated arachidonic acid (AA) metabolites, malondialdehyde (MDA), and tocopherols were then quantified by high-performance liquid chromatography (HPLC). Diamide treatment partially decreased the amount of reduced glutathione (GSH) content and induced a subsequent decrease in peroxidase activity. However, formation of 12-hydroxy eicosatetraenoic acid (12-HETE), the end-product of lipoxygenation of AA, increased. Formation of MDA, a marker of overall lipid peroxidation, was also enhanced. Furthermore, platelet alpha-tocopherol, but not gamma-tocopherol, significantly decreased. These results indicate that enhanced "basal" lipoxygenase activity, as a marker of specific AA oxygenation, may be linked to decreased platelet antioxidant status. PMID- 1762514 TI - Characterization of the coronary vascular responses to platelet-activating factor in the isolated perfused heart. AB - Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse in vivo and in vitro coronary vascular effects. In the present study, the coronary vascular responses to bolus injections of PAF were compared in rat hearts perfused under constant flow and under constant pressure. Low levels of PAF (1 pmol) produced vasodilatation only, while higher PAF concentrations (100 pmol) produced initial vasodilatation which was followed by a vasoconstriction under both experimental conditions. To determine species differences in PAF action, the effect of PAF was tested on perfused guinea pig hearts. Unlike in perfused rat hearts, only a dose-dependent vasoconstrictor response was observed in perfused guinea pig hearts following a bolus injection of 1 fmol to 10 pmol of PAF. The results from repeated injections of PAF indicated that depletion of vasoactive mediators induced by PAF or receptor desensitization may explain a failure of a second injection of PAF to initiate a vasoconstrictor response. After PAF injection, the coronary vascular response to leukotriene was not altered, indicating that the reduced vasoconstrictor effect of a second injection of PAF cannot be due to a reduced ability of the smooth muscle to constrict. The study demonstrates that similar coronary vascular responses to PAF are observed in perfused rat hearts under either constant flow rate or constant pressure and that some of the variable coronary vascular responses reported may be due to the difference between animal species. PMID- 1762515 TI - Modulation of polyunsaturated fatty acid content of triglycerides in rat pre adipocytes in culture. AB - Rat peri-renal and epididymal pre-adipocytes in culture undergoing triglyceride (TG) accumulation were incubated with oleic (18:1), linoleic (18:2), alpha linolenic (18:3 omega 3), arachidonic (20:4) and 4,7,10,13,16,19-docosahexaenoic (22:6 omega 3) acids in the presence of 0.8 microM insulin. The fatty acids were incorporated in cellular TG with relative enrichments over control from 1.4-fold for 18:1 to greater than 40-fold for 18:3 omega 3. Greater than 80% of fatty acids taken up were incorporated into cellular TG. The balance was distributed, in decreasing amounts, into phospholipids, unidentified intracellular constituents, and ketone bodies. The P/S ratio of cellular TG was at least an order of magnitude lower than that of the external milieu for both cell types and for all treatment groups, including controls. Doubling the concentration of treatment fatty acid increased its incorporation into cellular TG. However, it did not affect the accumulation of the other fatty acids in TG. Epididymal cells consistently acquire a higher proportion of treatment fatty acids in cell TG than peri-renal cells. Pre-adipocytes with polyunsaturated fatty acids (PUFA)-enriched TG is a potential model for the study of PUFA metabolism in these types of cells. PMID- 1762516 TI - Trans fatty acids. 4. Effects on fatty acid composition of colostrum and milk. AB - trans Isometric fatty acids of partially hydrogenated fish oil (PHFO) consist of trans 20:1 and trans 22:1 in addition to the trans isomers of 18:1, which are abundant in hydrogenated vegetable oils, such as in partially hydrogenated soybean oil (PHSBO). The effects of dietary trans fatty acids in PHFO and PHSBO on the fatty acid composition of milk were studied at 0 (colostrum) and 21 days postpartum in sows. The dietary fats were PHFO (28% trans), or PHSBO (36% trans) and lard. Sunflower seed oil (4%) was added to each diet. The fats were fed from three weeks of age throughout the lactation period of Experiment 1. In Experiment 2 PHFO or "fully" hydrogenated fish oil (HFO) (19% trans), in comparison with coconut oil (CF) (0% trans), was fed with two levels of dietary linoleic acid, 1 and 2.7%, from conception throughout the lactation period. Feeding trans containing fats led to secretion of trans fatty acids in the milk lipids. Levels of trans 18:1 and trans 20:1 in milk lipids, as percentages of total cis + trans 18:1 and cis + trans 20:1, respectively, were about 60% of that of the dietary fats, with no significant differences between PHFO and PHSBO. The levels were similar for colostrum and milk. Feeding HFO gave relatively less trans 18:1 and trans 20:1 fatty acids in milk lipids than did PHFO and PHSBO. Only low levels of cis + trans 22:1 were found in milk lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762517 TI - Dietary fat composition influences fatty acid composition of milk fat globule membrane in lactating cows. AB - Milk fat globule membranes are derived directly from the apical plasma membrane of mammary epithelial cells. To evaluate the effect of dietary fat on mammary membranes, we determined the fatty acid composition of the milk fat globule membrane in lactating dairy cows fed diets supplemented with fats of different fatty acid composition, or infused intravenously with soy oil emulsion. A preliminary survey, using an abbreviated preparation procedure (membranes isolated at 48,000 x g-max for 15 min), yielded about 45% of the total membrane fatty acids that could be recovered by centrifuging at the same speed for 120 min, and showed that changes in fatty acid composition of membranes reflected dietary fatty acids to some extent. Dietary palmitic acid increased the content of 16:0 in the membranes. A high corn diet increased ruminal formation of t18:1, and its level increased to 12% of membrane fatty acids. Infusion of soy oil emulsion increased 18:2 membrane content, and decreased the levels of 18:1 and 20:4. All treatments decreased the ratio of unsaturated/saturated fatty acids as compared to controls, whereas the ratio of polyunsaturated/saturated fatty acids was increased by feeding a high corn diet or by infusing soy oil. The ratio of 18:2/c18:1 increased from 0.31 to 1.0 after infusing soy oil for 4 days. The fatty acids of membranes isolated upon 120-min centrifugation were slightly more saturated. The differences were not sufficiently large, however, to affect overall results significantly. PMID- 1762518 TI - Tocopherol contents of lipoproteins from frozen plasma separated by affinity chromatography. AB - We investigated whether freezing and storage of plasma altered alpha-tocopherol levels of whole plasma or the lipoprotein fractions derived from such plasma. Plasma from 24 men, at each of two collection periods, was frozen at -20 degrees C for six weeks, then high-density lipoproteins (HDL) were separated from low- plus very low-density lipoproteins (LDL-VLDL) by heparin affinity chromatography. Whole plasma and the lipoprotein fractions were analyzed for alpha-tocopherol content and compared to counterparts from fresh plasma. Freezing and storage did not reduce alpha-tocopherol levels of plasma or the lipoprotein fractions. alpha Tocopherol values from fresh and frozen plasma were highly correlated for both plasma (period 1, r = 0.94; period 2, r = 0.93) and the LDL-VLDL fractions (periods 1 and 2, r = 0.97). Percent distribution of alpha-tocopherol between the two lipoprotein fractions was comparable for lipoproteins derived from fresh and frozen plasma. Under the storage conditions used in this study, plasma can be frozen for at least six weeks prior to lipoprotein fractionation with no detectable detrimental effects on alpha-tocopherol content of either plasma or lipoproteins. PMID- 1762519 TI - Diet-induced type IV-like hyperlipidemia and increased body weight are associated with cholesterol gallstones in hamsters. AB - Male Syrian hamsters (60-70 g) were fed purified diets containing 5% fat (American Fat Blend) and 15% fiber with or without 0.3% cholesterol (0.86 mg/kcal), for 12 weeks. Hamsters fed the cholesterol-supplemented challenge diet revealed a major increase in plasma triglyceride between 9 and 12 weeks, whereas plasma cholesterol (which reflected body weight dynamics) increased three-fold up to nine weeks and plateaued (342 +/- 22 vs. 122 +/- 5 mg/dL). The greatest increases in cholesterol occurred in the very low density lipoprotein (VLDL) and high density lipoprotein (HDL2) fractions. Gallstone incidence was similar (69% vs. 78%) for cholesterol-supplemented vs. control hamsters, but the type of stones differed. Of the cholesterol-supplemented hamsters with gallstones, 45% had cholesterol stones and 55% had pigment stones. Only pigment stones were seen in control hamsters. Hamsters with cholesterol stones were 25% heavier and transported most cholesterol in VLDL (33 +/- 5%), approximately double that in VLDL of cholesterol-supplemented hamsters with no stones (19 +/- 3%) or cholesterol-supplemented hamsters with pigment stones (21 +/- 3%). Hamsters with pigment stones or no stones (regardless of diet fed) transported the majority of their cholesterol in HDL2 (44%), whereas this figure was only 27% in hamsters that developed cholesterol stones. Thus pigment stones develop routinely in hamsters fed casein-based purified diets. Adding dietary cholesterol resulted in cholesterol gallstones only in those hamsters that gained the most weight and whose terminal VLDL/HDL cholesterol ratio exceeded 1.0, not unlike the lipoprotein profile of obese humans who develop cholesterol gallstones. PMID- 1762520 TI - Metabolism of meadowfoam oil fatty acids in mice. AB - Meadowfoam oil is unusual because over 95% of the fatty acids are 20- and 22 carbon aliphatic acids with cis double bonds located principally at the 5- and/or 13-position. Since little information is available on the metabolism of the 5c 20:1 and 5c,13c-22:2 fatty acids, an exploratory study in mice was conducted to investigate the metabolism of purified samples of the free fatty acids isolated from meadowfoam oil, and to determine the effect of meadowfoam oil on weight gain and tissue lipid composition. Mice fed diets containing 5% by wt of the purified 5c-20:1 or 5c,13c-22:2 for 6 days exhibited no apparent physiological problems. Total liver lipids from mice fed the purified fatty acid diets contained mean values of 2.0% 5c-20:1 and 2.1% 5c,13c-22:2; total heart lipids contained 1.7% 5c 20:1 and 10.7% 5c,13c-22:2. Liver total phospholipids from mice fed a 5% meadowfoam oil diet for 19 wk contained 1.4% 5c-20:1 and 1.9% 5c,13c-22:2. There was no evidence of desaturation, elongation or retroconversion. Weight gain for mice fed the meadowfoam oil diet for 19 wk was similar to mice fed corn oil, and was higher than for mice fed hydrogenated cottonseed oil. Considering the high 5c 20:1 and 5c,13c-22:2 content of the diets, the percentages of these fatty acids in mouse tissue lipids from both the short- and long-term studies were low. Weight gain was surprisingly good since the meadowfoam oil diet was essential fatty acid-deficient. Results of this initial investigation suggest that the 5c 20:1 and 5c,13c-22:2 fatty acids were utilized primarily for energy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762521 TI - Prostaglandin synthesis and fatty acid composition of phospholipids and triglycerides in skeletal muscle of chicks fed combinations of flaxseed oil and animal tallow. AB - Chicks were fed isocaloric and isonitrogenous diets containing 6% (w/w) added fat consisting of various proportions of animal tallow and flaxseed oil (FSO). No differences among treatments were seen in growth rate, muscular deposition of protein and lipids nor in the muscle phospholipid (PL) and triglyceride (TG) contents. Prostaglandin (PG)E2 synthesis in isolated skeletal muscle was depressed significantly by feeding FSO or by treatment with naproxen (6-methoxy alpha-methyl-2-napthaleneacetic acid), an inhibitor of PG synthesis. The changes associated with diet may be related to differences in the fatty acid composition of muscle lipids. Levels of saturated fatty acids in muscle PL and TG were relatively insensitive to dietary treatments. Monounsaturated fatty acid levels were significantly lower in the FSO-fed groups. FSO diets caused significant depression in muscle PL 20:4 omega 6 and almost completely inhibited 22:5 omega 6 incorporation. FSO diets decreased ratios of omega 6/omega 3 fatty acids and increased the unsaturation index of muscle PL. Muscles of chicks fed FSO showed increased levels of 18:3 omega 3, and of its derivatives 20:4 omega 3 and 22:5 omega 3. These results suggest that FSO inhibits PG synthesis and modifies the fatty acids of PL and TG of chick muscle. These changes may have implications for PG-dependent and/or membrane-dependent processes in muscle metabolism. PMID- 1762522 TI - Distribution among tissues of intravenously administered sucrose octaoleate. AB - The distribution of [14C]oleate label in rat tissues in the 6 hr after intravenous administration of sucrose octa[14C]oleate (7.5 mg; SuO8) was compared with that observed after administration of [14C]triolein. The [14C]oleate label, whether injected as triolein emulsion, or as chylomicrons obtained from donor animals, rapidly cleared from the serum; only 10% or less remained in the serum 15 min after injection. Labeled SuO8 disappeared less rapidly from the serum; about one-third of the dose was present after 15 min, and after 120 min 14% remained. In the liver, there was an initial greater accumulation of fatty acid label when an emulsion of either triolein or SuO8 was given rather than the chylomicrons. The octaester continued to accumulate in the liver throughout the 6 hr of study, and 78% of the initial dose was present at that time. By contrast, although one-third of the triolein, as of SuO8, was found in the liver shortly after injection, levels subsequently decreased; at 6 hr, 12% of the label remained associated with that organ. A small portion, up to 8% of the acid label, whether administered as chylomicrons or as a triolein emulsion, was found in the epididymal fat pads. Smaller amounts, usually 1% or less, of the [14C]oleate label were found in fat pads following the injection of labeled SuO8. In a separate study, the levels of acid label in the liver and spleen were monitored for 21 days following the intravenous administration of [14C]SuO8. There was an initial accumulation of approximately half of the injected lipid label in the liver and one-quarter in the spleen. By day 21, the level in the liver had decreased to one-third of that administered, while the level in spleen remained at one-quarter. PMID- 1762523 TI - The excretion and characterization of intravenously administered olestra. AB - Although sucrose octaoleate that is consumed is neither digested or absorbed, following intravenous injection it is found mainly in the liver. Olestra is a mixture of the hexa-, hepta-, and octaesters of sucrose. To follow the metabolic fate of intravenously administered [14C]sucrose-labeled olestra, we measured its urinary elimination, and the rate of excretion of 14C in the feces, and characterized the 14C-labeled material that appeared in bile. The fecal excretion for days 4-14 after dosing was found to be first order with the half-life of the injected olestra being 5.0 +/- 0.5 days. The 14C recovered in the bile was soluble in chloroform. Two-dimensional thin-layer chromatography autoradiograms of the biliary lipid showed the pattern of the biliary 14C to be essentially the same as that of the dosed olestra. Biliary excretion and subsequent fecal egestion of essentially unhydrolyzed sucrose esters is the principal route for the removal of intravenously administered olestra. Only traces of 14C were found in the urine. PMID- 1762524 TI - Interaction between dietary proteins and lipids in the regulation of serum and liver lipids in the rabbit. Effect of fish protein. AB - Purified diets varying in dietary protein, namely casein (CA), soy protein (SP), fish protein (FP), and lipid origin (corn oil (CN), coconut oil (CO)) were fed to rabbits to evaluate the effects of protein and fat source, as well as protein lipid interactions, on serum total, lipoprotein and hepatic lipid levels. Dietary proteins and lipids exerted a separate effect on serum total cholesterol (C), very low-density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol to high density lipoprotein cholesterol (LDL-C/HDL-C) ratio. Hence, CA increased serum cholesterol compared to SP, while coconut oil enhanced serum and VLDL-C, and decreased LDL-C/HDL-C compared to corn oil. Dietary proteins interacted with dietary lipids to modulate HDL-C levels. Thus, FP maintained a high level of HDL-C regardless of lipid origin, compared to CA and SP whose HDL-C levels were decreased by corn oil, compared to coconut oil. A dietary protein lipid interaction was also observed in the regulation of liver cholesterol levels. Coconut oil, compared to corn oil, decreased liver cholesterol in rabbits fed FP, whereas hepatic cholesterol concentration was unaltered by dietary lipid source in CA- and SP-fed rabbits. These results demonstrate that dietary proteins act synergistically with dietary lipids to regulate cholesterol metabolism in the rabbit. PMID- 1762525 TI - The effects of tricaine methanesulfonate (MS-222) on plasma nonesterified fatty acids in rainbow trout, Oncorhynchus mykiss. AB - The effects of tricaine methanesulfonate (MS-222), a commonly used fish anesthetic, on plasma nonesterified fatty acid levels (NEFA) were examined in rainbow trout, Oncorhynchus mykiss. Total NEFA levels declined with increasing duration of exposure to MS-222. Most of the decline in total NEFA was due to decreases in saturated fatty acids (14:0, 16:0 and 18:0). The fatty acid displaying the most rapid response to exposure to MS-222 was 20:5n-3. The lower plasma NEFA levels in anesthetized fish may be explained by depressed lipolysis in the presence of the anesthetic. PMID- 1762526 TI - The nurse executive and AIDS. PMID- 1762527 TI - Lengthening light; decreasing dark--nursing at the winter solstice. PMID- 1762528 TI - Medicaid reimbursements to nurse practitioners: the current status in Massachusetts. PMID- 1762529 TI - Research commentary: testimony--Special Commission on Nursing Practice. PMID- 1762530 TI - [Physical and technical problems of radiotherapy of malignant neoformations]. AB - Re-equipment of the radiotherapy clinics, the design of new facilities and methods of tele- and brachytherapy, the use of unconventional radiations, and computerization of the entire technological treatment process form the basis for raising the efficacy of radiotherapy and ensuring its quality. The clinics need a lot of high-qualified specialists: physicists, mathematicians, and x-ray technicians. PMID- 1762531 TI - [Medical radiation physics and informatics]. PMID- 1762532 TI - [Detectors of ionizing radiation and image converters in medicine]. AB - Radiation receivers used in medicine for image visualization and measuring the radiation characteristics are considered. The main attention is focussed on modern image converters for x-ray diagnosis and thermoluminescent detectors for dosimetry. PMID- 1762533 TI - [Concept of radiation safety in radiodiagnosis and therapy]. PMID- 1762534 TI - [Physical-technical and medical aspects of therapeutic effects of electromagnetic irradiation]. PMID- 1762535 TI - [Physical-technical problems of ultrasonic diagnosis]. PMID- 1762536 TI - [Problems in the design of physiotherapeutic fiber-optics light sources]. AB - The authors review tendencies in the application of fiber-optic laser coherent irradiation and monochromatized incoherent sources as phototherapy devices. Analyze the most important factors of the visible light impact on the biological tissues. Show that incoherent monochromatized light with a spectrum specially matched with the absorption spectrum of the biological molecules can produce a physiological effect comparable to that of laser radiation. PMID- 1762537 TI - [Development of a monitoring system for radiodiagnostic devices]. AB - The authors review the possibilities of the application of the "man-machine" theory to the radiodiagnostic unit. Show implementation of the theory with special reference to the basic purpose of the unit RENA 50-6 MP equipped with the microprocessor system of monitoring. PMID- 1762538 TI - [Problems in operating computerized tomographs]. PMID- 1762539 TI - [Foundation of the Association of Medical Physicists]. AB - The paper is concerned with foundation of the Association of Medical Physicists under the Physical Society of the USSR. The Association is to unite the efforts of physicists, chemists, mathematicians and engineers working at the medical institutions and engaged in physical problems of medicine and in the design of appropriate instruments, devices, equipment and materials in industry, at the Institutes of the Academy of Sciences, and at higher educational establishments. The functions of medical physicists and their roles in consolidation of the relations between medicine and natural sciences and engineering are discussed. PMID- 1762540 TI - [The course on medical physics]. AB - The definition of medical physics is given, the main directions of the course are described, and some practical examples are provided. Analysis is made of the status of the problem concerned with teaching medical physics. PMID- 1762541 TI - [A course on medical technology for future physicians]. AB - It is suggested that senior-course medical students be trained in the use of the most popular medical devices and equipment intended for functional diagnosis and treatment and that a specialized course including lectures, methodological aids and specialized practice in medical equipment be organized. PMID- 1762542 TI - [Experience in the use of disposable packages for sterilization of medical items]. AB - Disposable packages for medical items sterilization, manufactured by Vipack Medical (Finland) have been tested to demonstrate that it is strongly advisable that they may be employed at the treatment and prophylactic institutions of the USSR. The nomenclature of the packages holding promise for use has been delimited. PMID- 1762543 TI - [An improved model of portable illuminator OC-150-M1 for the equipment fitted with light guides]. PMID- 1762544 TI - [Medical physics and conversion]. PMID- 1762545 TI - [Approaches and problems in the development of radiodiagnostic equipment]. AB - The authors analyze the current status of technical equipment of different sections of roentgenology. Note shortcomings in the units manufactured and in the equipment of the sections of radiodiagnosis. Make conclusions about the tasks the Association of Medical Physicists of this country face. PMID- 1762546 TI - Stress revisited. 2. Systemic effects of stress. Introduction. PMID- 1762547 TI - The major mechanisms of stress. PMID- 1762548 TI - The connection between steroid receptors and stress protein (hsp90). PMID- 1762549 TI - Stress in affective disorders. PMID- 1762550 TI - Genetic basis of increased sensitivity to environmental stress in hypertension. PMID- 1762551 TI - The effects of stress, emotion, and behavior on the heart. AB - The relationships between emotional status, neurohormonal control and the cardiovascular function are reviewed. In the first part of this paper, we reviewed (1) the pathways between brain and heart, physiology of the defense reaction and the role of the autonomic nervous system in the mediation of the effects of stress; (2) the cardiac manifestations of emotional stress, and (3) the role of stress and the influence of circadian variations in the occurrence and development of myocardial ischemia, myocardial infarction and sudden death. In the second part, we discussed the relationship between behavior, coronary heart disease and particularly the role of the so-called type A behavior and hostility. Finally, we emphasize the importance of life-style changes to improve the prognosis of coronary disease and to limit the progression and ultimately to cause a regression of atherosclerosis. Thus, it appears that a transdisciplinary approach associating cardiologists, neuroscientists and behavior scientists will help to devise more effective strategies for the prevention and early therapy of cardiovascular disease. PMID- 1762552 TI - Cellular and molecular changes in the heart during stress or exercise. PMID- 1762553 TI - Molecular design and modeling: concepts and applications. Part B. Antibodies and antigens, nucleic acids, polysaccharides, and drugs. PMID- 1762554 TI - Molecular modeling of antibody combining sites. AB - Each of the six CDRs of Gloop2 is shown with the modeled structure in. Overall, the results obtained using the combined algorithm are similar in accuracy to those achieved using the canonical method of Chothia et al. However, the canonical method is limited to those loops where the key residues identified by Chothia are present. With the number of antibody structures currently available, it is not possible to classify CDR-H3 into canonical ensembles. Additionally, a small percentage of examples in the remaining CDRs do not match the current canonical classifications and the protein engineer may well wish to mutate the key residues, precluding the use of Chothia's method for modeling the resulting conformation. Thus the best approach appears to be to use Chothia's method (at least to model the backbone conformation) when the loop to be modeled is represented in the database of canonical structures. Any other loops, either unrepresented among the known canonicals (including CDR-H3), or where mutations have been made to the key residues, may then be modeled by the combined algorithm presented here. PMID- 1762555 TI - X-ray crystallographic analysis of free and antigen-complexed Fab fragments to investigate structural basis of immune recognition. PMID- 1762556 TI - Use of two-dimensional 1H nuclear magnetic resonance to study high-affinity antibody-peptide interactions. PMID- 1762557 TI - Computer modeling of combining site structure of anti-hapten monoclonal antibodies. PMID- 1762558 TI - Nuclear magnetic resonance for studying peptide-antibody complexes by transferred nuclear Overhauser effect difference spectroscopy. PMID- 1762559 TI - Isotope-edited nuclear magnetic resonance studies of Fab-peptide complexes. PMID- 1762560 TI - Reductive methylation and carbon-13 nuclear magnetic resonance in structure function studies of Fc fragment and its subfragments. PMID- 1762561 TI - Modeling of antibody combining sites. PMID- 1762562 TI - Design and production of bispecific monoclonal antibodies by hybrid hybridomas for use in immunoassay. PMID- 1762563 TI - Catalytic antibodies. PMID- 1762564 TI - Antibody catalysis of concerted, carbon-carbon bond-forming reactions. PMID- 1762565 TI - Computer simulation of DNA supercoiling. AB - Major goals of this research are to comprehend and visualize the detailed three dimensional arrangements of supercoiled DNA. Attention has been focused in the initial stages on mathematical procedures to generate the spatial coordinates of the B-DNA double helix constrained to specific spatial pathways and on simple energy models of chain conformation. The new treatment of superhelical DNA in terms of parametric curves is an important first step in being able to generate and examine tertiary structure systematically. The location of every residue is implicitly determined by the equation of the closed curve, with the number of computational variables sharply reduced compared to the number required for explicit specification of all chain units. Furthermore, the constraints of ring closure in cyclic chains and/or the end-to-end limitations on constrained open chains are automatically satisfied by the formulations (cubic B-splines and finite Fourier series) chosen in this work. The predicted conformations of elastic DNA do not appear to be tied to either the form of chain representation or the computer simulation method. Significantly, two very different minimization and modeling approaches come to the same structural conclusions. The most stable configurations of the closed circular elastic DNA model are found to be interwound superhelices that are critically dependent on the specified linking number difference. The total elastic energy is proportional to the imposed linking number difference, and beyond the critical linking number difference separating the circular and figure-eight forms, the writhing number of the DNA superhelices is directly proportional to delta Lk. The measured proportionality constant between Wr and delta Lk, however, is somewhat greater than that deduced from experimental observations of plectonemically interwound DNA chains and an assumed structural model. Furthermore, at large delta Lk, the interwound structures appear to curve. The treatment of the DNA double helix as an ideal elastic rod is clearly incorrect. The chain cannot bend with the same ease in all directions. The degree of bending observed in atomic level models is also tied to the angular twist so that the presumed partitioning of bending and twisting components is in error. Furthermore, the local chain bending and twisting are base sequence dependent, with certain residues able to flex more symmetrically than others. The polyelectrolyte character of the DNA is additionally expected to govern the overall folding of the chain and to influence the local secondary structure. The next step in this work is to compare the properties of such "real" DNA with conventional elastic models.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762566 TI - Molecular modeling to study DNA intercalation by anti-tumor drugs. PMID- 1762567 TI - Molecular modeling in mutagenesis and carcinogenesis. PMID- 1762568 TI - Protein engineering of single-chain Fv analogs and fusion proteins. PMID- 1762569 TI - Transfer RNA with double identity for in vitro kinetic modeling of transfer RNA identity in vivo. PMID- 1762570 TI - Molecular modeling and electron diffraction of polysaccharides. PMID- 1762571 TI - Molecular design and modeling of protein-heparin interactions. AB - The methods and approaches taken to investigate heparin-apoE peptide interactions have involved a series of steps, including (1) identification of the heparin binding domains of apoE, (2) determination of the minimal amino acid sequence regions involved in heparin binding, heparin-induced conformational changes, and stability of apoE peptide structures in solution, (3) modeling of these peptide and oligosaccharide structures, and (4) examination of their behavior during molecular dynamics calculations to determine if the modeled complexes simulate the results of the solution study. The heparin-binding regions of apoE were determined by fragmentation of the protein and identification of the heparin binding fragments by ligand-blotting procedures using 125I-labeled heparin. Studies with synthetic peptide fragments of various lengths and dot-blot procedures with 125I-labeled heparin identified the minimal residues critical for heparin-binding and CD studies established the prominent secondary structures of these domains. These studies also showed that heparin binds to the apoE(211-243) and apoE(129-169) regions to induce and stabilize beta-strand and alpha-helical peptide conformations. Secondary structure algorithms were used to identify the specific residues with the highest probabilities of forming alpha-helix and beta strand structures. Based on the predictive algorithms, the apoE(211-234) and apoE(129-159) structures were built using the Insight program and their molecular interactions with various heparin oligosaccharide models were investigated by molecular dynamics. In agreement with the solution studies in the presence of salt, the molecular dynamics studies showed that the oligosaccharides stabilized the beta-strand and alpha-helical peptide configurations against simulated thermal denaturations. Further modeling studies are in progress to examine the mechanism of the heparin-induced increase in ordered structure of these peptides. PMID- 1762572 TI - Computer-assisted rational drug design. PMID- 1762573 TI - Pattern recognition methods in rational drug design. AB - Pattern recognition methods have much to offer the drug designer, particularly as the calculation and collation of data, both biological and physicochemical, becomes easier with the widespread use of computer databases, molecular modeling systems, and property prediction packages. Some of the techniques, however, suffer from difficulties in interpretation and the dangers of chance effects have received little attention. The wider use and understanding of these methods is expected to enhance their utility in drug design. Finally, it should be mentioned here that these methods are becoming applied increasingly in other areas of pharmaceutical research, e.g., the analysis of clinical data, and that new techniques for analysis continue to be developed and applied in this field. PMID- 1762574 TI - Pharmacophore for nicotinic agonists. PMID- 1762575 TI - Construction of single-chain Fv derivatives monoclonal antibodies and their production in Escherichia coli. PMID- 1762577 TI - On assessing the impact of medical information: does MEDLINE make a difference? PMID- 1762576 TI - Humanization of monoclonal antibodies. PMID- 1762578 TI - Probabilistic diagnosis using a reformulation of the INTERNIST-1/QMR knowledge base. I. The probabilistic model and inference algorithms. AB - In Part I of this two-part series, we report the design of a probabilistic reformulation of the Quick Medical Reference (QMR) diagnostic decision-support tool. We describe a two-level multiply connected belief-network representation of the QMR knowledge base of internal medicine. In the belief-network representation of the QMR knowledge base, we use probabilities derived from the QMR disease profiles, from QMR imports of findings, and from National Center for Health Statistics hospital-discharge statistics. We use a stochastic simulation algorithm for inference on the belief network. This algorithm computes estimates of the posterior marginal probabilities of diseases given a set of findings. In Part II of the series, we compare the performance of QMR to that of our probabilistic system on cases abstracted from continuing medical education materials from Scientific American Medicine. In addition, we analyze empirically several components of the probabilistic model and simulation algorithm. PMID- 1762579 TI - Probabilistic diagnosis using a reformulation of the INTERNIST-1/QMR knowledge base. II. Evaluation of diagnostic performance. AB - We have developed a probabilistic reformulation of the Quick Medical Reference (QMR) system. In Part I of this two-part series, we described a two-level, multiply connected belief-network representation of the QMR knowledge base and a simulation algorithm to perform probabilistic inference on the reformulated knowledge base. In Part II of this series, we report on an evaluation of the probabilistic QMR, in which we compare the performance of QMR to that of our probabilistic system on cases abstracted from continuing medical education materials from Scientific American Medicine. In addition, we analyze empirically several components of the probabilistic model and simulation algorithm. PMID- 1762580 TI - Validation, clinical trial, and evaluation of a radiology expert system. AB - The PHOENIX Radiology Consultant is a rule-based expert system which assists physicians in planning radiological work-up strategies. This article describes the methods used to create and validate the system's knowledge base. The feasibility and acceptability of PHOENIX were tested for two years in a clinical trial. During this period, the system was used 1,421 times, an average of 13.7 times per week, primarily by medical students and nonradiologist physicians. Much of the system's use occurred at night and on weekends, when the radiology department was not fully staffed. Several physicians were enlisted to further evaluate the utility of the system. The results of their evaluation indicate that an expert system that helps physicians select diagnostic-imaging studies can serve as a useful and informative component of a radiology information system, and is particularly useful for medical students and physicians in training. PMID- 1762581 TI - A Medical Text Analysis System for German--syntax analysis. AB - Much information about patients is stored in free text. Hence, the computerized processing of medical language data has been a well-known goal of medical informatics resulting in different paradigms. In Gottingen, a Medical Text Analysis System for German (abbr. MediTAS) has been under development for some time, trying to combine and to extend these paradigms. This article concentrates on the automated syntax analysis of German medical utterances. The investigated text material consists of 8,790 distinct utterances extracted from the summary sections of about 18,400 cytopathological findings reports. The parsing is based upon a new approach called Left-Associative Grammar (LAG) developed by Hausser. By extending considerably the LAG approach, most of the grammatical constructions occurring in the text material could be covered. PMID- 1762582 TI - The design and management of national morbidity surveys. AB - This paper describes the three major morbidity surveys in general practice which have been conducted in England and Wales. In it, the evolution of the recording method is traced from the patient summary card of the first survey to the diagnostic index of the second and third surveys and finally, to the fully computerised recording programme to be used in the fourth survey due to start in September, 1991. Issues relating to the capture of social data, the use of diagnostic terms and the value of obtaining data over a 12 month period are discussed. PMID- 1762583 TI - WING--entering a new phase of electronic data processing at the Giessen University Hospital. AB - At the Giessen University Hospital electronic data processing systems have been in routine use since 1975. In the early years developments were focused on ADT functions (admission/discharge/transfer) and laboratory systems. In the next decade additional systems were introduced supporting various functional departments. In the mid-eighties the need to stop the ongoing trend towards more and more separated stand-alone systems was realized and it was decided to launch a strategic evaluation and planning process which sets the foundation for an integrated hospital information system (HIS). The evaluation of the HELP system for its portability into the German hospital environment was the first step in this process. Despite its recognized capabilities in integrating decision support and communication technologies, and its powerful HIS development tools, the large differences between American and German hospital organization, influencing all existing HELP applications, and the incompatibility of the HELP tools with modern software standards were two important factors forcing the investigation of alternative solutions. With the HELP experience in mind, a HIS concept for the Giessen University Hospital was developed. This new concept centers on the idea of a centralized relational patient database on a highly reliable database server, and clinical front-end applications which might be running on various other computer systems (mainframes, departmental UNIX satellites or PCs in a LAN) integrated into a comprehensive open HIS network. The first step towards this integrated approach was performed with the implementation of ADT and results reporting functions on care units. PMID- 1762584 TI - A versatile test for clustering and a proximity analysis of neurons. AB - A test for nonrandom patterns in populations of "cells" of binary attributes is formulated for applications in settings where it is impossible or impractical to completely specify the adjacency matrix, as in circumstances involving enormous numbers of cells and/or censored data. Applications are made to problems concerning spatial distributions of specially labeled cells in nervous system research. PMID- 1762585 TI - The octave approach to EEG analysis. AB - A "tonal" approach to EEG spectral analysis is presented which is compatible with the concept of physical octaves, thus providing a constant resolution of partial tones over the full frequency range inherent to human brain waves, rather than for equidistant frequency steps in the spectral domain. The specific advantages of the tonal approach, however, mainly pay off in the field of EEG sleep analysis where the interesting information is predominantly located in the lower octaves. In such cases the proposed method reveals a fine structure which displays regular maxima possessing typical properties of "overtones" within the three octaves 1-2 Hz, 2-4 Hz and 4-8 Hz. Accordingly, spectral patterns derived from tonal spectral analyses are particularly suited to measure the fine gradations of mutual differences between individual EEG sleep patterns and will therefore allow a more efficient investigation of the genetically determined proportion of sleep EEGs. On the other hand, we also tested the efficiency of tonal spectral analyses on the basis of our 5-year follow-up data of 30 healthy volunteers. It turned out that 28 persons (93.3%) could be uniquely recognized after five years by means of their EEG spectral patterns. Hence, tonal spectral analysis proved to be a powerful tool also in cases where the main EEG information is typically located in the medium octave 8-16 Hz. PMID- 1762586 TI - Diagnostic consultations: a speech-act theoretical reconstruction for the design of consultation systems. AB - In this paper the theory of speech acts is applied for a structural reconstruction of medical diagnostic consultations. The reconstruction provides the conceptual model for a research prototype of a consultation tool which is expected to play a mediating role between the participants in the professional diagnostic discourse. Preliminary results of the design will be outlined. PMID- 1762587 TI - Important law change affects titling of nurses in advanced practice. PMID- 1762588 TI - [Grouping of beta-hemolytic streptococci isolated from clinical specimens and their sensitivity to penicillin G]. AB - 260 beta hemolytic streptococci were isolated from clinical specimens sent to Microbiology Laboratory, Faculty of Medicine, Anadolu University between September 1988 - September 1989. They were grouped according to their sensitivity to bacitracin and trimethoprim/sulfamethoxazole (SXT) and also serologically. Of 260 isolates, 83.8% were group A, 1.2% group B, 6.5% group C, 3.5% group D and 5% were group G. All of 121 group A isolates confirmed serologically were susceptible to bacitracin. Excluded 9 strains, all of them were resistant to SXT. Other groups were mostly resistant to bacitracin. While group C and G generally were susceptible to SXT, B and D were resistant. Streptococci were documented according to distribution of clinical specimens. From throat 191 group A, 16 group C, 1 group D and 11 group G; from nose 7 group A; from pus 19 group A, 4 group D and 1 group G; from vagina 1 group A, 3 group B, 2 group D and 1 group G; from urine 2 group D; from blood 1 group C were isolated. All isolates were tested for penicillin G sensitivity by Kirby-Bauer disc diffusion method. While one of three group B strains and four of eight group D strains were resistant to penicillin G, all the other isolates were susceptible to penicillin G. PMID- 1762589 TI - [Antibiotic sensitivity tests of methicillin-resistant staphylococci]. AB - In this study, 231 Methicillin-Resistant Staphylococcus (MRS) and 76 Methicillin Susceptible Staphylococcus (MSS) strains were investigated. 23 antibiotics were tested by using Modified Kirby-Bauer Technique. The highest resistance ration in MRS strains were found for lincomycin, clindamycin and ampicillin with the ratios of 61.0%, 59.3%, and 56.2% respectively. And the lowest resistance ratios were measured for vancomycin, ciprofloxacin and ofloxacin 0.5%, 8.2%, 10.8% respectively. It was found that, resistance of MRS strains to 17 antibiotics were significantly higher than resistance of MSS strains, but not for sulbactam ampicillin, cefoperazone, ceftriaxone, vancomycin, ciprofloxacin, ofloxacin and netilmicin. PMID- 1762590 TI - [Penicillin resistance in gonococcal urethritis]. AB - In this study, we researched the resistance of gonococci to penicillin among 30 patients who had urethral discharge because of gonococcal urethritis, between 1990 January and 1990 September at SSK Ankara Hospital. We established 26.6% of isolated 30 Neisseria gonorrhoeae species resistant to penicillin. PMID- 1762591 TI - [Neonatal sepsis]. AB - We noticed coagulase positive staphylococcus is the most common pathogen in the neonatal sepsis in our neonatology unit. We followed 22 cases with neonatal sepsis. Blood cultures revealed coagulase staphylococcus in 9 cases, coagulase negative staphylococcus in 6 cases, Pseudomonas spp. in 5 cases, E. coli in 1 case, Klebsiella spp. in 1 case. The most common symptom was apnea. CRP positivity was noted in 15 cases (68.2%) while increase in immature/total neutrophil ratio was observed in 12 cases (54.5%). However, we detected leukopenia in 2 cases (9.1%). Also, the birthweight of the cases died due to neonatal sepsis were below 2000 gr. PMID- 1762592 TI - [Female genital tract tuberculosis]. AB - The frequency of female genital tract tuberculosis exhibits a parallelism that of pulmonary tuberculosis in the population. It is generally found in reproductive women, but also occurs in postmenopausal ones. Its frequency has declined since the introduction of specific treatment, but it is discovered incidentally during the course of an investigation for infertility. The most common location is in fallopian tubes. In the Department of Pathology from the Medical School of Cumhuriyet University 11 female genital tract tuberculosis have been described between the years of 1984 and 1990. In this study, age, symptoms, localizations and pathological findings of these cases have been reviewed. PMID- 1762593 TI - [HBsAg positivity in patients with prediagnosed viral hepatitis and hospital personnel]. AB - HBsAg was determined in 172 sera from 106 persons with clinically pre-diagnosed viral hepatitis (Group I) and 66 hospital personnel (Group II). In the investigation, the passive haemagglutination test was used. Positive results were obtained in 29.2% of Group I and 7.6% of Group II. HBsAg positivity in two groups was found to be differ significantly. PMID- 1762594 TI - [The effect of some antibiotics on primary antibody response]. AB - In this study, effect of four broad spectrum antibiotics (sodium cefoperazone, sulbactam-ampicillin, mezlocillin, rifamycin) on primary antibody response. Therefore, sheep red blood cells were injected into total 25 rabbits in control and experiment groups. Hemolysin levels were titrated in serum specimens prepared from blood specimens taken before the experiment and taken three weeks after the last antigen injection. It was found that statistically significant in all the experiment groups rather than control (p less than 0.05). PMID- 1762595 TI - [Stability of cefazolin sodium as eyedrops in various solutions]. AB - Cephazolin sodium prepared with four different solutions (NaCl 0.9%, Protagent, Liquifilm and phosphate buffer) to be used as eye drops, was evaluated as to its physicochemical features at +4 degrees C, +37 degrees C and at room temperature and its activity in terms of minimal inhibition concentration. In conclusion, cephazolin sodium prepared with artificial tears at acidic pH can be kept for 3 days at room temperature and at +4 degrees C without any loss of its activity. PMID- 1762596 TI - [Urogenital Chlamydia trachomatis infections]. AB - Urogenital Chlamydia trachomatis infections are the most common sexually transmitted diseases which have shown a significant increase in the last few years. This organism presents a major health problem in many countries. It is recognized as the cause of both complicated and uncomplicated infections in men, women and infants passing through an infected birth canal. Tissue culture is accepted as the gold standard in the diagnosis of chlamydial infections. But, since this technique is expensive and cumbersome, antigen detection tests such as DFA and EIA are more widely used. Tetracyclines and erythromycins are the first choice antimicrobials in the treatment of chlamydial infections. PMID- 1762597 TI - [Colony-stimulating factors]. AB - The colony-stimulating factors are glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells and the function of mature blood cells. They are claimed to be used in the therapy of some hematologic disorders as well as infectious diseases in recent years. PMID- 1762598 TI - [The importance of the enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of tuberculosis]. AB - The remainders of tuberculosis infection are still existing as a problem, as important and threatening as AIDS (acquired immune deficiency syndrome), especially in underdeveloped countries. The diagnosis of tuberculosis infection frequently creates problems which is related to clinical, radiological and bacteriological investigations and it requires a lot of time consumption. The ELISA procedure is a sensitive and reproducible technique and it doesn't require complex equipment. Recently, this technique provides hopeful results for the serodiagnosis of tuberculosis. PMID- 1762599 TI - [Why study pharmacy?]. PMID- 1762600 TI - [Non-steroidal anti-inflammatory drugs--more than inhibitors of prostaglandin synthesis]. PMID- 1762601 TI - [Treatment of endemic goiter, hypo- and hyperthyroidism]. PMID- 1762602 TI - [Deglutition disorders. Definition, diagnosis and therapy]. PMID- 1762603 TI - [The effects of licorice--not harmful to health?]. PMID- 1762604 TI - Correlation of preS antigens and clinical status during chronic hepatitis B virus infection. AB - The serum kinetics of preS1 and preS2 antigens has been evaluated in 38 serial samples from eight patients with chronic active (CAH) or chronic persistent (CPH) hepatitis, followed for 2-7 years (mean 4.4 years) in whom liver biopsy was performed at intervals, and in 46 samples from ten asymptomatic HBsAg carriers followed for 4-5 years (mean 4.6 years). Four patterns of preS behaviour have been observed: (1) persistently positive preS1 and preS2; (2) disappearance of preS2; (3) disappearance of both preS1 and preS2; and (4) persistently negative preS1 and preS2. Pattern 4 has been observed exclusively among healthy carriers, while seven out of eight chronic patients exhibited either pattern 1 or 2. Among the chronic patients, preS2 disappearance was accompanied or followed by alanine aminotransferase (ALT) normalization. The correlation of preS antigens with conventional viral replication markers showed that 100% of hepatitis B virus (HBV)-DNA-positive and 86.6% of HBeAg-positive sera were preS1/preS2 positive, while 61% of HBV-DNA-negative and 64% of HBeAg-negative sera were preS1/preS2 negative. Our data suggest that continuous monitoring of preS antigens in follow up sera will allow for an improved prognostic evaluation of chronic HBV infection. PMID- 1762605 TI - Prevalence of antibodies to recombinant hepatitis C virus protein C100-3 and of elevated transaminase levels in blood donors from Northern Germany. AB - Antibody to recombinant hepatitis C virus protein C100-3 (anti-C100-3) was assayed by a first generation enzyme-linked immunosorbent assay (ELISA; Ortho Diagnostics) in 116,700 blood donors who had not been tested before. Total prevalence of repeatably positive donors was 0.72% (n = 842). Prevalence increased significantly from 0.42% at 18-27 years of age to 1.26% at greater than or equal to 58 years. Donors with elevated serum transaminase levels were significantly more often anti-C100-3 positive, but in 98.7% of donors with current or 99.1% with previous transaminase elevations, anti-C100-3 was not found. Elevated transaminases were more often associated with positive anti-C100 3 in females than in males. However, in the total donor population no significant differences of anti-C100-3 prevalence were found between the sexes. During follow up at three subsequent blood donations, 1.08% of donors were positive at least once, but only 0.48% were consistently positive. The cutoff of the Ortho ELISA was not in the minimum of the frequency distribution between positive and negative samples, but far within the range of the negative signals, i.e. the test is likely to produce a significant number of false-positive results. In retesting positive samples with two ELISAs from other producers only a 22% to 65% agreement was found. In a low prevalence group such as German blood donors, the first generation ELISAs for anti-C100-3 produced more false than specific positive results. Most donors with elevated alanine aminotransferase (ALT) are anti-C100-3 negative. PMID- 1762606 TI - Effect of vasodilation and vasoconstriction on microvascular pressures in skeletal muscle. AB - The effect of topically applied papaverine (PAP) and norepinephrine (NE), on the microvascular pressure distribution was studied in the cremaster muscle of anesthetized rats. The cremaster muscle was exteriorized into a tissue bath containing Krebs bicarbonate buffer, and microvessel diameters and pressures were measured using a video caliper and the resistance servo-null method, respectively. Pressures were measured in the 1st through 4th branch order arterioles (1A to 4A) and 1st through 4th branch order venules (1V to 4V). Resistances were calculated across each segment from pressure gradients and 1A blood flow which was estimated from red cell velocities. PAP (10 microM) produced approximately a 15% decrease in arteriolar pressures with a concomitant increase in venular pressures of between 15 and 50%. In contrast, NE (0.1 microM) significantly increased arteriolar pressure by approximately 30% and decreased venular pressure by about 25%. Changes in systemic pressure during treatment with PAP and NE were small or insignificant and could not account for the observed changes in microvascular pressure. Significant dilation was observed in 3A, 4A, and 3V vessels after papaverine. In comparison, NE caused significant constriction in all vessel orders except 4V. PAP decreased resistance across all segments between 1A and 4V by 22-42% and increased venular resistance by almost 400%. NE increased resistance in all microvascular segments with the largest changes occurring in 2A to 3A (+276%) and 4A to 4V (+277%) segments. These data demonstrate that PAP and NE induce significant and opposite changes in arteriolar and venular pressures. Such network alterations in microvascular pressure should be considered when evaluating microvascular reactivity and exchange in the presence of vasoactive agents. PMID- 1762607 TI - Ischemia-reperfusion induced gastric mucosal microcirculatory alterations in the rat. AB - The aim of this study was to determine the gastric microcirculatory alterations occurring during reperfusion after a period of ischemia and the possible role of oxyradicals in the microcirculatory disturbance. An in vivo microscopy technique was used to observe the superficial mucosal blood flow during reperfusion. After reperfusion, mucosal blood flow resumed quickly and then slowed with eventual cessation of flow. Thirty minutes of ischemia followed by reperfusion resulted in cessation of flow in 50 +/- 4% and 81 +/- 8%, of the capillaries in the microscopic field at 15 and 30 min, respectively, after reperfusion. During this mucosal microcirculatory change, numerous white thrombi were observed flowing in the mucosal microvessels. In rats pretreated with allopurinol to inhibit oxyradical formation, blood flow was maintained to a significant and markedly greater extent. Study of the submucosal microvasculature after reperfusion revealed a marked delay in transit of a fluorescein-albumin bolus from terminal submucosal arterioles through the mucosal microvasculature and back to submucosal collecting venules. Submucosal vascular diameter change could not explain the altered mucosal blood flow. These findings indicate that there is marked slowing and cessation (in many microvessels) of gastric mucosal blood flow during reperfusion after a period of ischemia, and that the obstruction to flow occurs in the mucosal microvessels. The results of the study with allopurinol suggest that oxygen-derived free radicals generated by xanthine oxidase may play a major role in the genesis of this gastric mucosal microcirculatory disturbance. PMID- 1762608 TI - Dynamic structure of blood flow in microvessels. AB - The present article summarizes the author's perennial research on the flow of red blood cells in microvessels, the major determinant of rheological properties of blood in the microcirculation. Two main patterns of blood flow structure in microvessels, in the smallest arteries and veins and in the capillaries are described. The red cell concentration (hematocrit) in the blood flowing in microvessels undergoes regular alterations with changes of blood flow rate and vessel diameter in the microvascular beds. Further, the red blood cell concentration and flow velocity gradients are found in the cross-section of microvessels that should considerably affect the blood rheological properties in the microcirculation. In addition, radial displacements and blood velocity fluctuations of red cells in the flow are discovered in the larger microvessels during ischemic decrease of blood flow rate. The main factor disturbing the normal blood flow structure, and hence the normal rheological properties of blood, is the intravascular aggregation of red blood cells, which is to be diagnosed and eliminated in patients with blood rheological disturbances. PMID- 1762609 TI - The effect of smoking and menopause on the small blood vessels. AB - The small blood vessels were examined in 31 premenopausal and 31 postmenopausal women. In each group there were 14 non-smokers and 17 smokers of age groups 35-45 and 45-59. The women underwent full gynecological examination. Blood pressure was normal in each. The small blood vessels were examined by capillaroscopy of conjunctivae and nailfolds, by oscillometry of the radial artery, skin thermometry of the wrist and terminal phalanx, and by capillary fragility. When all abnormalities in non-smokers were compared with those in smokers in the menopausal groups, a significant difference was found, (Table 4), to the disadvantage of the smokers. PMID- 1762610 TI - Hepatic microvascular regulatory mechanisms. XI. Effects of serotonin on intralobular perfusion and volumetric flowrates at the inlet of periportal and outlet of centrivenous sinusoids. AB - A normotensive (1.0 microgram per 100 g b.w.) or hypotensive (10.0 micrograms per 100 g b.w.) dose of serotonin (5-HT) was administered endoportally while changes in microcirculation at the inlet and outlet regions of hepatic lobules were measured on-line using quantitative in vivo microscopy. The number of sinusoids with decreased (cellular) flow also was counted to index intralobular perfusion in video recordings of microvasculature examined off-line. The normotensive and hypotensive doses of 5-HT elicited decreases in intralobular perfusion within periportal and centrivenous sinusoids. Hypoperfusion was accompanied by a transient decrease in volumetric flowrate (Q) at the outlet of centrivenous sinusoids in 40% of normotensive and in 100% of hypotensive rats. At the inlet of periportal sinusoids, Q was depressed in 75% of hypotensive and in 27% of normotensive rats. The remainder of these segments had either an increase or no change in Q at the inlet and outlet. These results suggested that during conditions of 5-HT induced (lobular) hypoperfusion: (a) Q at the inlet is maintained in 73% of normotensive rats by redistribution of intralobular blood flow, and decreased in all but 25% of hypotensive rats as a function of transient reductions in total hepatic (arterial) and/or portal (venous) blood flow(s), and (b) Q at the outlet is depressed in 40% of normotensive rats by apparent increases in flow redistribution and resistance to flow generated during sinusoidal constriction, whereas in all hypotensive rats this mechanism is aggravated by decreased total hepatic (arterial) and/or portal (venous) inflow(s). Therefore, although the initial time course for microvascular responses tended to be similar for normo- and hypo-tensive doses of 5-HT, quantitative differences in regional flow distribution and Q emphasize (a) the importance of intra- and extra-hepatic determinants in the regulation of blood flow within hepatic (unit) lobules, and (b) the presence of microvascular heterogeneity within these lobular units. PMID- 1762611 TI - Capillary recruitment and heterogeneity of perfused capillary distribution in dog myocardium. AB - To estimate functional diffusion distances, the distribution of perfused capillaries was calculated in dog myocardium. A fluorescent dye was injected via a femoral vein in 6 anesthetized, open-chest dogs, and passed once through the coronary circulation (23 +/- 3 s). In 6 animals the dye circulated 4-20 min. In 6 animals the dye circulated for one pass following 2-3 min of asphyxia. The heart was then removed and frozen. Frozen sections from the left ventricule were cut, illuminated to excite the dye to fluoresce, and photographed. They were then stained by silver methenamine to mark all capillaries. The density of all capillaries was compared to that of capillaries containing fluorescent label. The distributions of capillaries were estimated by morphometry. In one pass of the normoxic coronary circulation, 66(+/- 4 SE)% of subepicardial and 60(+/- 4)% of subendocardial capillaries were detectably labeled. Their distribution approached a random pattern, and maximal distances to the nearest labeled capillary were lengthened by 50% compared to all capillaries. With multiple passes of the dye, or with asphyxia 76-79% of the capillaries were detectably labeled and their distribution approached the ordered pattern of the total capillary bed. We speculated that the unlabeled capillaries represented a spatially heterogeneous blood flow reserve. PMID- 1762613 TI - The quality of care. PMID- 1762612 TI - Understanding OSHA's bloodborne pathogen standard. PMID- 1762614 TI - Fusobacterium necrophorum sepsis in a six-year-old girl. PMID- 1762615 TI - The use of alternative therapies by HIV-positive patients attending the St. Louis AIDS Clinical Trials Unit. PMID- 1762616 TI - Centrifugal pump support for repair of thoracic aortic injury. AB - Spinal cord ischemia and the potential for paraplegia are always of concern during operations for repair of traumatic thoracic pseudoaneurysm. Patients who experience hypotension, loss of intercostal blood supply, or normothermic aortic cross clamp times greater than 30 minutes are more likely to become paraplegic. The preservation of renal perfusion is also a concern. PMID- 1762617 TI - New concepts in asthma. PMID- 1762618 TI - The differential diagnosis of asthma. AB - The clinical hallmarks of asthma are wheezing and reversibility. Any disease that impairs air flow through obstructed airways may cause wheezing. Patients with true asthma may give a history of allergy and past attacks of dyspnea and wheezing occurring when exposed to allergens, inhaled irritants, upper respiratory infection, cold and humid air, exercise, and emotional stress. When encountering a wheezing dyspneic patient who does not report such a history, it behooves the physician to entertain the possibility that the patient may have a disease other than asthma. Chronic bronchitis, pulmonary emphysema, cardiogenic pulmonary edema pulmonary emboli, aspiration of gastric contents, and upper airway obstruction are the common causes of nonasthmatic wheezing. In almost every instance a wide spectrum of easily obtainable data, particularly historical, are available to alert the physician that the patient's dyspnea and wheezing are not due to asthma. Laboratory data are also readily available to buttress the correct diagnosis. PMID- 1762619 TI - The role of mast cells in bronchial asthma: mechanisms and possible therapeutic implications. AB - The role of mast cells in human biology is important and complex. They probably play a dual role both in protecting the host and in causing disease symptoms. For example: mast-cell-mediated vasopermeability is an important manifestation of asthma, but it also provides access of antibody and other blood factors which are brought to the tissue and help in defense. Therefore, these cells, with their abundant mediators, may play an important role in both homeostasis and disease. PMID- 1762620 TI - Occupational airway diseases. PMID- 1762621 TI - The role of atopy in asthma. AB - Allergy plays an important role in chronic asthma. Aeroallergens, both indoor and outdoor, provide a constant source of bronchial inflammation that increases bronchial hyperreactivity. This increased reactivity lowers the threshold of response to nonspecific triggers of asthma flares such as viral infections, pollutants, and cold air. Asthma is a chronic inflammatory disease in much the same way that the rheumatic diseases are. In that respect, therapy should be directed at reducing inflammation, as it is in the rheumatic diseases. Along these lines, newer approaches to asthma therapy should emphasize steroids as first-line treatment. In this way, therapy is targeted against the underlying inflammation that causes the bronchial obstruction, rather than treating with bronchodilators such as theophylline and B agonists. The effect of such continuous antiinflammatory therapy is decreased airway hyperresponsiveness, which has obvious clinical benefit. PMID- 1762622 TI - Asthma in children and its management: an update. PMID- 1762623 TI - Pulmonary function testing in bronchial asthma: standard and emerging techniques. AB - Despite the myriad of tests available to characterize bronchial asthma, the simple forced expiratory spirogram remains the most straight-forward and reliable technique to diagnose the disorder and gauge its severity. When combined with bronchodilator and bronchial challenge testing, a wide range of clinical situations can be evaluated, even in the office setting. A well-performed forced expiratory spirogram remains the cornerstone of pulmonary function testing; the emergence of the additional analytic techniques described holds the promise of even greater utility in the future. PMID- 1762624 TI - Bone marrow failure disorders. PMID- 1762625 TI - Cloning and characterisation of an immunodominant major surface antigen of Echinococcus multilocularis. AB - A lambda gt11 cDNA expression library from mRNA of Echinococcus multilocularis protoscolices has been constructed in Escherichia coli Y1090. Immunoscreening with pooled sera obtained from patients suffering from E. multilocularis disease revealed 5 reactive clones. By partial DNA sequence comparison all clones proved to encode the same gene. The complete cDNA sequence of the clone pEM10 with the largest insert of 2.2 kb was determined and an open reading frame of 1.7 kb could be described. The derived amino acid sequence shares 42.6% identity with human microvillar cytovillin found in the membranes of placenta and carcinoma tissues. The coding region of the cDNA of pEM10 was amplified by polymerase chain reaction (PCR) and cloned in frame into expression vector pGEX-3X. Immunoblot analysis revealed the expression of a recombinant antigen of 65 kDa and a protein with the same molecular weight was also found in the lysate of E. multilocularis protoscolices. In contrast, the protein was absent from hydatid fluid or larvae of Echinococcus granulosus. By means of immunofluorescence studies this immunodominant antigen could be located in the germinal layer of brood capsules and in the tegument of E. multilocularis protoscolices. The fusion protein was purified and used for diagnostic purposes in immunoblot. The diagnostic value of this antigen is discussed. PMID- 1762626 TI - A repetitive DNA probe specific for a North American sylvatic genotype of Trichinella. AB - A partial genomic DNA library constructed in pUC 13 using DNA from a sylvatic isolate of Trichinella spiralis (T. spiralis T5) was differentially screened with radiolabeled homologous genomic DNA and with DNA from T. spiralis T1. One clone was identified and designated pUPB-3.7 which, by slot blot and Southern blot analyses, reacted specifically with T. spiralis T5 DNA and did not cross-react with DNA from any other T. spiralis genotype. The 482-bp repetitive sequence which is 70% rich in A and T residues, comprises at least 2.7% of the parasite genome and can detect as little as 0.4 ng of DNA. When used to assess the prevalence of T. spiralis T5 in Indiana wildlife, DNA from 19 of 20 independently obtained sylvatic isolates reacted positively with the pUPB-3.7 probe indicating that within this geographical locality, T. spiralis T5 is the predominating genotype in wild mammals. PMID- 1762627 TI - Phospholipids and protein kinase C in acetylcholine-dependent signal transduction in Ascaris suum. AB - Quantitatively, the major phospholipid in the muscle of the nematode Ascaris suum was found to be phosphatidylcholine (lecithin). Stimulation of Ascaris muscle with acetylcholine or the agonists carbachol and levamisole increased the level of phosphorylcholine, 1,2-diacylglycerides and phosphatidic acid. Increased levels of these compounds, together with the demonstration of phospholipase C activity, suggest that phospholipid hydrolysis may be associated with the ACh response of the muscle via second messenger pathways. In other tissues, diacylglycerides and phosphatidic acid have been reported to regulate protein kinase C activity. Protein kinase C activity also was demonstrated in the muscle of Ascaris. For optimal activity the kinase was dependent upon Ca2+, unsaturated 1,2-diacylglyceride and phospholipid. All of the data are in accord with the possible involvement of a second messenger system being operative in the ACh stimulated contraction of Ascaris muscle. PMID- 1762628 TI - Characteristics of thymidine transport in Giardia intestinalis trophozoites. AB - The transport of thymidine by the protozoan parasite Giardia intestinalis was examined at 0 degrees C. This temperature prevented attachment of the cells to vessel walls, so that a rapid sampling technique could be used. Thymidine influx (distinguished from gross uptake) was readily measurable at 0 degrees C and was specific and saturable. The transporter appears to be a facilitative carrier, exhibiting a high affinity for thymidine (Km = 50 microM). Thymine and uracil were the most effective inhibitors (Ki = 30 microM and 45 microM, respectively), followed by thymidine, deoxyuridine and uridine (Ki = 64-96 microM). Cytosine, cytidine and deoxycytidine were not inhibitory, even at high concentrations. The data indicate that the oxygen at position 4 of the pyrimidine ring is essential for recognition by the transporter, whereas the 5-methyl group of thymine is unimportant. The furanose ring appears not to be recognized, since D-ribose was non-inhibitory and uridine and deoxyuridine were equally inhibitory but less so than uracil and thymine. This carrier probably mediates the transport of uracil, as well as uridine and thymidine, although influx of the base remains to be measured. PMID- 1762629 TI - Heterogeneity of the genes encoding the major surface glycoprotein of Leishmania donovani. AB - The major surface glycoprotein of Leishmania (GP63) is present on all known species of Leishmania and likely plays an integral role during the infection of macrophages in the mammalian host. To identify regions of GP63 which may be of functional significance, the nucleotide sequence of a gene encoding GP63 of Leishmania donovani was determined and compared to the sequences reported for GP63 genes of Leishmania major and Leishmania chagasi. The GP63 nucleotide and predicted protein sequence was highly conserved among the 3 species despite their diverse geographical distribution. L. donovani GP63 is encoded by a multigene family and the gene locus contains at least 7 tandemly repeated genes and at least 3 genes which are dispersed from the tandem array. In addition, polymerase chain reaction and Southern blot analyses demonstrated that there was size heterogeneity within the pro-peptide coding regions of the multiple GP63 genes of L. donovani and that such genes were expressed concurrently in the promastigote life stage. PMID- 1762630 TI - An 85-kilodalton surface antigen gene family of Trypanosoma cruzi encodes polypeptides homologous to bacterial neuraminidases. AB - We have determined the sequence of a cDNA (Tt34c1) encoding a Trypanosoma cruzi trypomastigote stage-specific 85-kDa surface glycoprotein (gp85). Within the peptide sequence of Tt34c1 are two 8-amino acid motifs, Ser-X-Asp-X-Gly-X-Thr Trp, that are characteristic of bacterial neuraminidases. Analysis of the Tt34c1 sequence predicts the presence of an amino-terminal signal sequence and a hydrophobic carboxy-terminus that is probably replaced by a glycosyl phosphatidylinositol membrane anchor. Gp85 is encoded by an extensive multigene family that is distributed throughout the genome and can be divided into subsets on the basis of oligonucleotide hybridisation patterns. By sequencing products of polymerase chain reaction (PCR) amplification of the 5' end of trypomastigote gp85 mRNA we show that multiple copies of the gene family are transcribed simultaneously in a trypanosome population. Comparison of the sequence of the PCR clones and another gp85 cDNA showed a highly conserved region 5' of the first methionine extending 180 nt into the coding sequence. Insertions and point mutations were observable outside these homologous sequences demonstrating the variant nature of the gp85 mRNAs. PMID- 1762631 TI - High homology between variant surface glycoprotein gene expression sites of Trypanosoma brucei and Trypanosoma gambiense. AB - The AnTat 11.17 variant surface glycoprotein (VSG) is synthesized in both metacyclic and bloodstream forms of Trypanosoma gambiense. We have characterized the AnTat 11.17 gene, and analyzed its expression site (ES) in the bloodstream form by Southern and Northern blotting with probes from the Trypanosoma brucei AnTat 1.3A VSG ES, and by run-on transcription. The AnTat 11.17 ES is located at the end of a 700-kb chromosome. It appears to contain all the genes (ESAGs, for Expression Site-Associated Genes) present in the AnTat 1.3A VSG ES, with the possible exception of ESAG 1. Limited nucleotide sequence analysis of ESAG cDNAs from the AnTat 11.17 ES shows considerable conservation with ESAGs of T. brucei. The transcription promoter of the AnTat 11.17 VSG ES, localized by virtue of the specific accumulation of promoter-proximal transcripts which occurs following UV irradiation, was found to be at the same relative position to the first ESAG (ESAG 7) as in AnTat 1.3A. PMID- 1762633 TI - Economic costs, cost-effectiveness, financing, and community-based drug treatment. PMID- 1762632 TI - Sequence of the knob protein of Plasmodium falciparum recognized by a monoclonal antibody. PMID- 1762634 TI - Economic costs of drug abuse. PMID- 1762635 TI - Cost-effectiveness of drug abuse treatment for primary prevention of acquired immunodeficiency syndrome: epidemiologic considerations. AB - The prevention of AIDS has justified recent increases in drug abuse treatment expenditures. Three of the epidemiologic considerations involved in assessing the cost-effectiveness of drug treatment for primary prevention of AIDS among IV drug users were discussed. First, the considerable geographic variation in the prevalence of the virus that causes AIDS suggests that areas with relatively low infection levels may be more cost-effective targets when allocating limited drug abuse treatment resources. Expansions and modifications in the current national HIV-1 serologic surveillance system will be needed to make informed resource allocation decisions. Second, when comparing the cost-effectiveness of two alternative treatment modalities or programs, the number of new HIV-1 infections does not appear to be an appropriate outcome measure. Serologic testing should be supplemented with self-reported drug use behaviors, with or without drug testing. Finally, significant opportunity costs may be associated with employing drug abuse treatment as the principal approach to primary prevention of HIV-1 infection among IVDUs, when alternative and complementary approaches are also effective. Specifically, treatment expansion is unlikely to be cost-effective when the demand for publicly funded treatment slots exceeds the number available and in communities where only a small minority of IVDUs are enrolled in treatment. PMID- 1762636 TI - Policy-relevant research on drug treatment. PMID- 1762637 TI - Community-based drug treatment reimbursement: progress and barriers. PMID- 1762638 TI - Financing treatment for substance abuse. PMID- 1762639 TI - Forecasting the cost of drug abuse treatment coverage in private health insurance. PMID- 1762640 TI - Health insurance coverage questions, public health surveys, and drug abuse. PMID- 1762641 TI - Economic cost of illicit drug studies: critique and research agenda. PMID- 1762642 TI - Economics and drugs: promises, problems, and prospects. PMID- 1762643 TI - Evaluating the cost-effectiveness of drug abuse treatment services. PMID- 1762644 TI - Cost-effectiveness of drug abuse treatment: relevant issues and alternative longitudinal modeling approaches. PMID- 1762645 TI - New perspectives on the benefit-cost and cost-effectiveness of drug abuse treatment. PMID- 1762646 TI - Planning and developing an academic curriculum in Israel. AB - The authors trace the development of academic curricula in nursing in Israel from the early 1960s to the present day. The foundation was laid with the first post basic programme in 1968, and the new basic nursing degree scheme was launched at Tel Aviv University in 1989. The initial success of this project has encouraged nursing schools to pursue means of upgrading their courses from diploma to degree level. PMID- 1762647 TI - Nurses' attitudes to elderly people: a survey of nursing homes and elderly care wards in an inner-London health district. AB - This paper is based on a survey of 104 nurses of varying grades and experience working with elderly people in nursing homes and hospitals in an inner-London health district. The aim was to establish the veracity of a hypothesis which stated that nursing home staff would express greater job satisfaction and perceive their environments more positively than hospital staff. Most nurses in all settings were satisfied with their work, although less than one-third reported their reason for applying for their current post as a preference for working with elderly people. The authors conclude that, although favourable views were recorded, the negativity and dissatisfaction expressed by the nurses is evidence of the low status and appeal of the specialty. PMID- 1762648 TI - Integrating research and practice. AB - The opinion that research is not a legitimate activity for nurses has support in and outside the profession. It has been argued that nursing is a simple art that is not enhanced by science, and that research hinders rather than facilitates the provision of quality nursing services. This paper will examine these arguments and relate them to current controversies in nursing theory, education, research and practice. PMID- 1762649 TI - Caring for dying patients in acute hospital wards: a review. AB - Evidence suggests that most people in Britain now die in hospital, or spend a period of their terminal illness there (1). People in the terminal stage of illness who are cared for in a hospice or at home are in the minority. Nurses working in busy acute hospital wards find that part of their role includes caring for dying patients. Given that the main responsibility of nurses working in the acute setting is to care for sick people receiving active treatment, it was decided to examine the experiences of these nurses when they were caring for terminally ill patients. The effects of the acute ward setting on the dying patient, relatives and friends will also be considered. A hospice has a specialist role in care of the dying. In contrast, a hospital emphasises cure (2). As it is inevitable that some hospitalised patients will die, nurses must be competent to care for them and patients must be confident of the care they will receive. This article will consider some of the problems of caring for the dying in the acute setting, as discussed in the literature, and will recommend improvements in practice. PMID- 1762650 TI - [Histological diagnosis of brain tumors: (18). Astrocytoma]. PMID- 1762651 TI - [Anterior decompression surgery of aged patients with cervical myelopathy]. AB - One hundred and thirty-nine patients with cervical myelopathy who underwent anterior decompression surgery were reviewed to determine the characteristics and surgical outcome in 26 elderly patients over the age of 65. The mean age of the aged group was 69.7 and that of the remaining 113 patients was 50.0. Extensive spur removal and interbody fusion with iliac bone graft were performed in all patients. Evaluation of clinical grades was based on the Japan Orthopedic Association Score (JOA score) on admission, at discharge and at the time of follow-up (mean 26.8 months). The improvement rate was calculated from Hirabayashi's formula at each point. Preoperatively, the mean duration of illness was longer and the mean JOA score was significantly lower in the aged group. Furthermore, low incidence of soft disc and multi-level lesions were characteristic for the aged. Final JOA score increased from 8.2 to 13.0 in the aged group, while that in the non-aged group increased from 10.5 to 14.8. These differences were statistically significant at each point. Excellent and good results which were designated as an improvement rate of 50% or more were obtained in 73.1% of the aged group, and in 79.6% of the non-aged group. Postoperative complications were slightly more frequent in the aged group, all of which, however, were dislocation of bone graft seen in 3 patients. As compared with the non-aged group, poorer surgical outcome in the aged group was attributed to preoperative poor clinical condition, long duration of preoperative symptoms, low incidence of soft disc herniation and multi-level lesions which were characteristic features for the aged patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762652 TI - [Phosphenes elicited by subcortical stimulation in man]. AB - Electrical stimulation of a point in the visual pathway can evoke a visual sensation which is called a phosphene. The phosphenes elicited by intracerebral stimulation were investigated in twenty-three subjects. One hundred and seven phosphenes were reported and all of them appeared in the visual field contralateral to the side of stimulation. The exception was a single case where a diffuse flashing sensation appeared in the whole visual field. Thirteen patients reported white phosphenes and nine patients reported coloured phosphenes. In the medial area (10-15 mm from the midline) of the occipital lobe, stimuli above the calcarine fissure resulted in phosphenes in the lower quadrant of the visual field. In the lateral area (16-32 mm from the midline), however, stimuli above the level of the calcarine fissure tended to produce phosphenes in the upper quadrant. These findings appear to conflict with traditional concept of the physiological anatomy of the visual pathway in man. The possible mechanism of this phenomenon produced by intracerebral stimulation is discussed in relation to the phosphenes produced by cortical stimulation. PMID- 1762653 TI - [Experimental study on brain reversibility following temporary regional cerebral ischemia; from the point of view of vessel behavior and histological changes]. AB - Using a middle cerebral artery occlusion model in adult cats, we investigated the ischemic time threshold for inflicting damage on cerebral vessel behavior and brain tissue. With the transorbital approach, a middle cerebral artery (MCA) was exposed and temporarily obstructed by a Zen's clip. Animals were divided into ten groups (each group: N = 8) according to the ischemic time of 10, 20, 30 minutes, 1, 2, 4, 6, 8, 12, 24 hours. Five hours after the recanalization, Evans' blue dye was injected intravenously and after further 30 minutes, the brain was fixed with transaortal perfusion for histological examinations. A cranial window was made above the ectosylvian gyrus which has poor anastomosis. The pial vessel behavior was observed through the cranial window and evaluated using an intravital microscope and a videoangiometer. Considering the correlation between functional change of vessel behavior and pathological change in the brain, the threshold time of ischemia inflicting irreversible damage was estimated. In the 30 minute ischemia group, deterioration of vessel behavior began to be observed as well as extravasation of Evans' blue dye. As the ischemic duration became longer, infarction and hemorrhage, which showed close correlation, increased. When the duration of ischemia was 6 hours, the infarcted area was significantly larger than that of the 4-hour ischemia group. Intracranial pressure (ICP) markedly increased as soon as recanalization took place. We think this phenomenon is due mainly to swelling. About three hours after recanalization, ICP further increased due to severe vasogenic edema in addition to the brain swelling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762654 TI - [Immunohistochemical expression of alpha-1-antitrypsin in human gliomas]. AB - The present paper describes the analysis of immunostaining patterns of four antibodies, alpha-1-antitrypsin (alpha-AT), glial fibrillary acid protein (GFAP), S-100 protein (S-100), and vimentin in 31 human gliomas. The gliomas were 10 astrocytomas, 10 anaplastic astrocytomas, and 11 glioblastoma multiforme tumors. The immunoreactivity for vimentin and alpha-AT that is one of the main proteinase inhibitors changed in proportion to the degree of histological malignancy. As alpha-AT was localized mainly in the cytoplasm of tumor cells and partially in extracellular spaces, it was thought to have been derived from tumor cells. Preparations immunolabelled with anti-GFAP and anti-S-100 showed no increasing loss of immunoreactivity parallel with increasing malignancy. PMID- 1762655 TI - [Immunomodulatory effects of interferons on target human gliosarcoma cells in the tumor-specific CTL- and LAK-mediated cytolysis]. AB - We compared the regulatory effects of interferon (IFN)-beta and IFN-gamma on the susceptibility of a human gliosarcoma line GI-1 to the attack of autologous cloned tumor-specific cytotoxic T-lymphocytes (CTL) and lymphokine-activated killer (LAK) cells. Preincubation of GI-1 cells with IFN-gamma caused augmented susceptibility to the cytotoxic attack of two autologous CTL clones, whereas IFN beta exhibited no such marked effect. On the other hand, preincubation with either IFN-beta or IFN-gamma made the GI-1 cells resistant to the attack of autologous LAK cells. Both IFNs augmented the surface expression of HLA class-I molecules on GI-1 cells. A monoclonal anti-HLA class-I antibody blocked the cytolysis by one CTL clone, but not by the other one. These results suggest that IFN-gamma exerts some different effect (s) from that of IFN-beta on the target GI 1 cells in their susceptibility to the CTL-mediated cytolysis, and that recognition mechanisms of target cells by the CTL are different from those by LAK cells. This draws our attention to IFN administration in adoptive immunotherapy against brain tumors using CTLs and LAK cells. PMID- 1762656 TI - [Three cases of non-traumatic acute subdural hematoma]. AB - The authors present three cases of non-traumatic acute subdural hematoma showing interesting clinical features and operative findings. Case 1: A-50-year-old male was admitted because of sudden headache and epileptic seizure. Computed tomographic (CT) scan showed a right thin subdural hematoma, but cerebral angiography demonstrated no pathological findings, that might cause acute subdural hematoma on the follow-up CT scans. The hematoma changed to a chronic one within only 15 days, which was proved by the operation. Case 2: A 52-year-old male was hospitalized because of loss of consciousness. CT scan revealed a right subdural hematoma without subarachnoid hemorrhage and cerebral angiography demonstrated a right middle cerebral artery aneurysm. The hematoma was surgically proved to be due to rupture of the aneurysm. Case 3: A 52-year-old male was admitted because of headache, vomiting and left motor weakness. CT scan showed a thick right subdural hematoma and right carotid angiography revealed two internal carotid artery aneurysms. It was surgically certified that the subdural hematoma was caused by a tear in a cortical artery attached to the dura, not by the rupture of the aneurysms. Clinical cause and pathogenesis of so-called "non traumatic" or "spontaneous" acute subdural hematomas were discussed, and the importance of emergency angiography for this condition is stressed. PMID- 1762657 TI - [Plasma cell tumor of the parieto-occipital bone; a case report]. AB - Plasmacytoma originating in the cranial bone is a rare disease. A report is presented of a case of plasmacytoma originating in the parieto-occipital region. The patient was a 62-year-old male with palpation of a parieto-occipital mass as chief complaint. He showed no neurological deficit. Ig-G in the serum was 2240 mg/dl, and M-protein (n-type) was demonstrated in the serum. Bence-Jones protein was negative and bone marrow was normal. Skull X-ray showed osteolytic change in the parieto-occipital region. CT scan and MRI demonstrated a markedly enhanced mass extending from the epidural to the subcutaneous space at the parieto occipital region. Common carotid angiography showed remarkable tumor stain flowing from the occipital artery, the superficial temporal artery, and the middle meningeal artery. Following embolization of the bilateral occipital artery, parieto-occipital horse shoe scalp incision was done. The tumor was elastic soft and bled easily around the margin of destroyed bone. Subtotal removal of the tumor was accomplished. The removed surgical specimen of the tumor was found to be plasmacytoma. The patient's postoperative course was favorable and no neurological deficit was found. Laboratory studies revealed a remarkable reduction of Ig-G in the serum to 1170 mg/dl. Six months after the operation, no signs of recurrence were seen on CT scan. Plasmacytoma originating in the cranial bone is so rare that only 18 cases have been reported to date. In these cases, laboratory studies have shown no evidence of anemia, Bence-Jones protein in urine, and abnormality of the bone marrow which are characteristic of multiple myeloma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762658 TI - [A case of sellar germinoma which was misdiagnosed as pituitary adenoma]. AB - The authors reported a rare case of sellar germinoma which was misdiagnosed as nonfunctioning pituitary adenoma. A 32-year-old woman was admitted to our hospital because of amenorrhea and disturbance of left visual acuity. She had become amenorrhagic after her second delivery two years before. Neurological examination revealed she was normal except for diminished left visual acuity (Rt. = 1.2, Lt. = 0.5). The general condition was good. Urine volume and its specific gravity were within normal range. Endocrinological examination showed hyperprolactinemia (PRL 72 ng/ml) accompanied with impairment of GH, TSH, LH and FSH's reserve. Basal levels and reserve of the blood cortisol were normal. AFP and hCG were within normal range. CT scan revealed a homogenously enhanced intrasellar tumor which had a suprasellar portion (vertical length: 15 mm). T1 weighted MRI revealed low intensity tumor, and T2 weighted image revealed high intensity tumor. Sagittal MR image with gadolinium enhancement showed the pituitary gland anterior to the tumor. Transsphenoidal removal was performed. The histological diagnosis was pure germinoma. After the operation, the intracranial and spinal disseminations were disclosed. Complete neuraxis irradiation resulted in the complete remission of the tumor. Sellar germinoma without diabetes insipidus is considered to be very difficult to diagnose preoperatively. However, the authors proposed that anterior shift of the pituitary gland in sagittal MR image may be a clue to the diagnosis of sellar germinoma. PMID- 1762659 TI - [Cavernous angioma of falx cerebri; case report]. AB - A first case of cavernous angioma of falx cerebri is reported. A 62-year-old woman who had a history of intermittent headache and dizziness was admitted to our hospital. On admission she had no neurological deficit, but CT scan showed a slightly high density tumor located beneath the falx cerebri. This was markedly and homogeneously enhanced by contrast medium. MRI showed a tumor with low intensity in T1-weighted image and high intensity speckled with low intensity in T2-weighted image. Angiogram revealed a faint tumor-stain fed by the bilateral pericallosal arteries at middle arterial to late venous phases. With the tumor attached to the lower edge, the falx was totally removed through a left front parietal craniotomy. Histologically the tumor was diagnosed as cavernous angioma and thought to have originated from the dura mater of the falx. A search in the literature revealed that only 7 cases of extracerebral cavernous angiomas excluding ones in the middle cranial fossa have been previously reported. Five of them were located at the tentorium cerebelli and two at the convexity. The MRI finding such as speckled mixed intensity may reflect the vascular lumens or their thromboses in the tumor. Angiographic finding such as faint tumor stain at middle arterial to late venous phases due to slow blood flow in the tumor are thought to be specific to intracranial cavernous angiomas. These findings are of particular importance in differentiating cavernous angiomas from meningiomas. PMID- 1762660 TI - [Total removal of hypothalamic glioma 15 years after irradiation of right optic glioma]. AB - Hypothalamic glioma was found in a 17 year old male patient 15 years after irradiation of right optic glioma. It was totally removed by surgery. He was first admitted to Ryukyu University Hospital at the age of 1 year and 11 months, with right exophthalmos and visual disturbance. Diagnosis was anterior type of right optic glioma. This was treated by irradiation (47 Gy). Follow-up CT scans revealed no regrowth in intraorbital and intracranial regions. At the age of 17 years, CT scan and MRI showed an enhanced mass in the hypothalamus above the suprasellar cistern. Total removal was performed by bifrontal interhemispheric trans-lamina terminalis approach. Histological diagnosis was pilocytic astrocytoma. Postoperatively, consciousness remained disturbed for 3 weeks because of infarction in the bilateral medial nucleus of the thalamus. Radical excision of hypothalamic glioma was reviewed in the literature. We concluded that such excision has a potentially good outcome, and should be attempted when circumstances indicate its feasibility. PMID- 1762661 TI - [A diffuse metastatic leptomeningeal carcinomatosis from gallbladder cancer; case report]. AB - We encountered a 72-year-old woman with diffuse metastatic leptomeningeal carcinomatosis, who first suffered from occipital pain and died about a month after onset. On postmortem examination, gallbladder cancer (adenocarcinoma) was found to be the primary disease. We focused on its frequency and the metastatic route. On the metastatic route, we obtained the following results: tumor cells infiltrated only the cerebrospinal fluid, but not the areas surrounding the gallbladder cancer (spine or spinal cord) or into the brain parenchyma. A comparative study of the state of cerebrospinal fluid between the ventricle and the subarachnoid space disclosed that the cerebrospinal fluid pressure, cell count, and CEA and CA 19-9 levels increased more in the intraventricular cerebrospinal fluid, especially when the CEA level was higher than that in the serum. On histopathological examination, tumor emboli were seen in choroidal vessels in the ventricular wall, and tumor cells existed sparsely around choroidal secretory vessels. These results were thought to support the theory of hematogenous metastasis as Little et al proposed. PMID- 1762663 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1762662 TI - [An intradural arachnoid cyst of the craniovertebral junction; a case report]. AB - An intradural arachnoid cyst of the craniovertebral junction possibly of traumatic origin is reported. A 59-year-old man was admitted to our hospital with a 10-month history of progressive gait disturbance. He had a history of head injury with a fracture of the occipital bone. Myelography revealed pooling of the contrast medium in the posterior fossa and on the dorsal sides of C1 and C2. Metrizamide-enhanced computed tomography also showed pooling at the same level. Magnetic resonance imaging indicated a large cystic lesion at the craniovertebral junction. Craniectomy of the posterior fossa and laminectomy of C1, C2 and C3 were performed, and an intradural cyst with thickened dura and arachnoid was found. The cyst wall was opened to communicate with the subarachnoid space. Histological findings of the specimen showed that the arachnoid was thickened. There are over 130 reports of intradural arachnoid cyst of the spine, but those of traumatic origin are rare, and cysts located in the intracranial to spinal region are extremely rare. PMID- 1762664 TI - Modulation of the transient potassium current in rat hippocampal neurones by cholecystokinin. AB - Cholecystokinin (CCK) affects neuronal excitability in a variety of in vivo and in vitro preparations, apparently by modulating a resting potassium conductance. The data presented here show that CCK (applied as CCK8-S) also affects the transient potassium current in hippocampal neurones, by changing the voltage dependence of the inactivation and activation of the current. The way in which the voltage dependence is changed can lead to either an enhancement of the current or an attenuation, depending upon the voltage protocol used. This effect of CCK does not desensitise over a time period of minutes, and may therefore be important in controlling neuronal excitability in the CNS. PMID- 1762665 TI - Vasoactive intestinal peptide levels in the hypothalamus and anterior pituitary do not change in association with the pre-ovulatory prolactin surge in the rat. AB - We examined whether vasoactive intestinal peptide (VIP) is involved in the preovulatory prolactin (PRL) surge in the rat. Ovariectomized adult rats implanted sc with an estradiol capsule 2 days previously were decapitated at hourly intervals between 1100-1800 h. The plasma PRL and luteinizing hormone showed an evident surge at 1700 h and 1800 h, respectively. The anterior pituitary PRL content was significantly lower at and after 1600 h than at 1100 h. However, there was no significant change in the VIP content in the suprachiasmatic nucleus, paraventricular nucleus, median eminence or anterior pituitary throughout the entire period of observation. Since all of these regions are known to be involved in the VIP synthesis and/or release, the present results appear to cast some doubt on previous studies reporting a significant role for VIP in the generation of the pre-ovulatory PRL surge. PMID- 1762666 TI - Secretion of gastric acid inhibited by oxytocin injected into the hypothalamic paraventricular nucleus in the rat. AB - Gastric acid output was examined following oxytocin injection into the hypothalamic paraventricular nucleus (PVN) or into the vagus nucleus (X) of the medulla in rats with insulin-hypoglycemia. Gastric acid output was reduced following the injection of nanomolar quantities of oxytocin into these nuclei, and the response was dose-dependent. It was also noted that there was a synergistic action on the response by the peptide between PVN and X. The acid response was blocked by section of the vagus nerve at the subdiaphragmatic level or by prior administration of atropine sulfate. These observations suggest that oxytocin in the PVN is active in suppressing gastric acid secretion, and the vagal response is characteristic of activation of the PVN and X. PMID- 1762667 TI - Effect of ovariectomy and estrogen replacement on hypothalamic, pituitary and peripheral blood beta-endorphin levels in the rat. AB - This study was initiated to detect possible changes in beta-endorphin (beta-EP) levels of the hypothalamus, anterior pituitary gland, and peripheral blood of rats after ovariectomy and estrogen administration. Attempts were also made to determine the correlation between peripheral and central levels of beta-EP. Twenty-six Sprague-Dawley rats were decapitated. Nine had intact ovaries (Gr. INT), and 17 were ovariectomized 3 weeks before they were killed. Nine of the ovariectomized rats received estradiol benzoate (EB) (Gr. EB) and the other 8 received peanut oil (Gr. OVX) prior to the decapitation. A beta-EP radioimmunoassay was used to analyze homogenates of the hypothalamus and anterior pituitary, and peripheral blood. In the hypothalamus, beta-EP levels were significantly lower in Gr. INT and Gr. EB than in Gr. OVX. In the pituitary gland and peripheral blood, beta-EP levels were significantly higher in Gr. INT than in Gr. OVX. Pituitary beta-EP levels did not vary between Gr. OVX and Gr. EB, although beta-EP levels in peripheral blood were significantly higher in Gr. EB than in Gr. OVX. No significant correlations were noted in beta-EP levels between the hypothalamus, pituitary gland, and peripheral blood in either Gr. INT, Gr. OVX, or Gr. EB. It appears that EB exerts different effects on beta-EP levels in the hypothalamus, anterior pituitary gland, and peripheral blood, and that beta EP levels in these regions may be independent of one another. PMID- 1762668 TI - Increased cerebrospinal fluid cyclo(His-Pro) content in schizophrenia. AB - Cyclo(His-Pro) (CHP) is a peptide endogenous to human brain and cerebrospinal fluid (CSF). In animal studies administration of exogenous CHP augments dopaminergic neurotransmission. To explore the role of this peptide in schizophrenia, a disease characterized by a hyperdopaminergic state, we have measured CSF CHP levels in control, never-medicated schizophrenics and medicated schizophrenics. Our data show a 53% increase in CSF levels of CHP in never medicated schizophrenics (p = 0.015), and a 25% increase in medicated schizophrenics when compared to controls. We speculate that CHP may contribute to the expression of hyperdopaminergic symptoms in schizophrenia. PMID- 1762669 TI - Indirect measures of memory in a duration-judgement task are normal in amnesic patients. AB - Nine amnesic patients of mixed aetiology were studied in a duration-judgement task that allowed three measures of memory to be obtained. On each trial of the task, subjects attempted to read a briefly flashed word and to estimate the duration of the flash. Both word identification and duration estimation differed as a function of prior study. Words that were previously studied were identified more often and were estimated to have been flashed for a longer duration than were words not previously studied. These priming effects were found in young subjects in Experiment 1 and in amnesic patients and age-matched control subjects in Experiment 2. Priming effects were normal in the amnesic patients, whereas these patients were severely impaired at recognizing the same words. Previous results have also shown that amnesic patients can perform normally on certain memory tests, including priming of word identification. These results show that priming of duration judgements can also be included in the category of indirect measures of memory that are spared in amnesia. PMID- 1762670 TI - Disentangling neglect and hemianopia. AB - In this paper we report findings which question the diagnosis of a hemianopia in B.Q., a 66-year-old lady who shows unilateral spatial neglect following a lesion to the right parietal lobe. The presence of a hemianopia has been indicated following two independent assessments of B.Q.'s visual fields. We examined B.Q.'s performance on a visuo-spatial task in which single or double stimuli were displayed left and right of a central fixation point. B.Q. failed to report left stimuli when the fixation point was continuously displayed (OVERLAP CONDITION). This performance is consistent with the suggestion of a left hemianopia as indicated by perimetric field testing. In a further condition the fixation point was extinguished prior to stimuli onset (GAP CONDITION). B.Q. consistently responded to left stimuli in the gap condition and also showed improved performance to right stimuli. Eye movements were recorded on a separate testing session, in which B.Q. showed a normal saccadic response to left targets in the gap condition, but not during the overlap condition. These results suggest that B.Q.'s failure to report left stimuli during field plotting is due to her neglecting left stimuli and not because she has a visual field defect. By using a testing procedure which reduces the severity of neglect B.Q. is able to respond to left stimuli. Reducing the severity of B.Q.'s neglect also abolishes the apparent hemianopia. Standard field plotting techniques which use a consistently displayed fixation point may not be appropriate for the testing of neglect patients' visual fields. PMID- 1762671 TI - Remission of somatoparaphrenic delusion through vestibular stimulation. AB - The effects of vestibular stimulation on somatoparaphrenic delusion were investigated in a patient suffering from a fronto-temporo-parietal infarction located in the right hemisphere. Transitory remission of the patient's delusional belief was consistently observed during unilateral vestibular activation obtained by means of cold-water irrigation of the left (contralesional) ear. PMID- 1762672 TI - Perceptual reference frames and visual field asymmetry for verbal processing. AB - Two experiments investigated the role of perceptual reference frames in producing visual field asymmetries for the recognition of consonant-vowel-consonant (CVC) nonsense syllables. In an upright stimulus display condition, both quantitative and qualitative visual field asymmetries replicated those obtained in earlier studies of CVC identification. When the stimulus displays were rotated 90 degrees clockwise or counterclockwise, there were no effects of presenting the CVC in relative LVF vs relative RVF stimulus locations. The contrast between results in the upright and rotated stimulus display conditions indicates that the LVF/RVF differences in the upright displays are attributable to the position of the CVC relative to the fovea, rather than relative to the perceptual reference frame. This finding is consistent with the interpretation that LVF/RVF differences in the upright condition are attributable to hemispheric differences in the processing of linguistic/phonetic information. PMID- 1762673 TI - Interhemispheric interaction in the split-brain. AB - An experiment is reported in which a split-brain patient (LB) was simultaneously presented with two words, one to the left and one to the right of fixation. He was instructed to categorize the right sided word (living vs non-living), and to ignore anything appearing to the left of fixation. LB's performance on this task closely resembled that of normal neurologically intact individuals. Manual response speed was slower when the unattended (left visual field) word belonged to the same category as the right visual field word. Implications of this finding for views of the split-brain syndrome are discussed. PMID- 1762674 TI - Unconscious perception of "extinguished" visual stimuli: reassessing the evidence. AB - When parietal-damaged patients fail to report a contralesional stimulus because of extinction, is this because the stimulus is not perceived, or because it is perceived but cannot reach conscious awareness? VOLPE et al. [10] reported an intriguing study that seemed to locate the problem at least partly in the transfer of information to conscious awareness. They showed patients with extinction pairs of stimuli, one in each hemifield. Although patients were predictably poor at reporting the identity of the contralesional stimulus, they were able to make accurate same/different judgements comparing the two stimuli. This was interpreted as evidence that both stimuli were perceived. In the present paper, we point out that the dissociation between identification and same/different matching could also be due to the possibility that less visual information about the contralesional stimulus is necessary to make a same/different judgement than to identify the stimulus, and that chance performance is considerably higher in the first than in the second type of task. In Experiment 1, we verified this by degrading one side of a stimulus display and "replicating" the dissociation with normal subjects. We also equated the amount of visual information needed for the two tasks by yoking the stimulus pairs on "different" trials of the same/different matching task with the choice pairs on a forced choice identification task. Under these conditions, the dissociation vanished. In Experiment 2, we administered these tasks to three parietal-damaged patients with extinction. When the original method was used, same/different matching was better than identification of the contralesional stimulus. With the forced choice identification method, the dissociation again vanished. PMID- 1762675 TI - Normal global-local analysis in patients with dorsolateral frontal lobe lesions. AB - The role of prefrontal cortex in the analysis of global and local levels of a visual stimulus was assessed by measuring reaction time to identify a target at one level or the other. Unlike patients with temporal-parietal lesions (STG), there were no global-local performance deficits in right or left prefrontal groups (RFL or LFL). Reallocation of attention to global and local levels was measured by examining changes in performance when the probability of a target appearing at one level or the other varied. While patients with lateral parietal lesions (IPL) have been shown to have deficits in these conditions, both RFL and LFL showed normal changes in performance. In sum, the performance of prefrontal groups differed from both IPL and STG groups but not from normal controls. These results strengthen previous arguments that posterior association cortex is crucial in responding to global and local levels of a pattern. PMID- 1762676 TI - Failure of object recognition due to a breakdown of figure-ground discrimination in a patient with normal acuity. AB - We report the case of a 71-year-old woman with partial cortical blindness attributable to cortical degeneration. Her visual acuity and colour perception were satisfactory but she was almost totally unable to recognize objects or people by sight. Investigations revealed a hitherto unreported dissociation between relatively well preserved shape discrimination and gravely impaired figure-ground discrimination. Thus, she was able to discriminate between a square and an oblong matched for total surface but she was unable to detect a simple shape against a pattern background. In a series of experiments it was shown that she could identify single printed capital letters of the alphabet relatively satisfactorily. She had no difficulty in identifying single, simple geometric shapes. By contrast, she was unable to discriminate configurations of two or three overlapping or concentric, simple, shapes. Strikingly she appeared to be "blind" to subjective contours and she was unable to perceive visual illusions normally. These deficits are interpreted to reflect a failure to achieve primitive organization of visual information rather than higher level perceptual impairments. The results are discussed in the context of physiological and computational models of early visual information processing. PMID- 1762677 TI - Differential effect of right and left hemispheric lesions on two memory tasks: free recall and frequency judgement. AB - We investigated the relationship between lateralized cerebral damage and two memory tasks; free recall and frequency judgement. Free recall is considered to be processed effortfully while frequency judgement is considered to be processed automatically (Hasher and Zacks). Nine right brain-damaged patients (RBD), nine left brain-damaged patients (LBD) and nine control subjects participated in this study. It was hypothesized that RBD would show an advantage over LBD on the free recall task, whereas LBD would show an advantage over RBD on the frequency judgement task. In accordance with our hypothesis, free-recall was more impaired in LBD than in RBD. In the frequency-judgement task, an effect of laterality of lesion was found in high (4-6) and low (0-1) frequencies, but not in the medium (2-3) frequencies. The anticipated LBD advantage was shown in judgement of the high frequencies, but unexpectedly RBD performed better than LBD in low frequencies. The results are discussed in terms of the relationship between effortful and automatic memory processes and cerebral lateralization. PMID- 1762678 TI - Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. AB - Attentional "set" shifting was assessed in a group of 20 neurosurgical patients with localized excisions of the frontal lobes, a group of 20 patients with unilateral temporal lobe lesions and a group of 11 patients who had undergone amygdalo-hippocampus removal. These three patient groups were compared with groups of both young (age-matched) and elderly normal control volunteers on a computerized test of visual discrimination learning involving both an intra- and an extra-dimensional shift. The frontal lobe group were selectively impaired in their ability to shift response set to a previously irrelevant dimension but not to shift attention to new exemplars of a previously relevant dimension. A similar pattern was observed in the elderly group of normal control volunteers. By comparison, both the temporal lobe patients and the amygdalo-hippocampectomy patients were unimpaired in their ability to perform either shift, although both groups had significantly prolonged selection latencies at the extra-dimensional shift stage of the task. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of a specific attentional set shifting deficit following frontal lobe damage. PMID- 1762679 TI - Fatty acids modulate excitability in guinea-pig hippocampal slices. AB - A variety of fatty acids produced sustained changes in excitability in the guinea pig hippocampal slice. Although each fatty acid was unique, a general pattern was evident. During a 30-min exposure, the synaptic potential was minimally affected, although population spike amplitude showed significant increases. With wash, synaptic efficacy increased. The increase in the synaptic potential was significant with arachidonic acid (100 microM), oleic acid (100 microM), myristic acid (250 microM) and capric acid (250 microM). Also with wash, the coupling between the synaptic potential and the population spike was reduced significantly for most of the fatty acids tested: arachidonic acid (50 microM, 100 microM), linoleic acid (100 microM) oleic acid (100 microM), stearic acid (100 microM), myristic acid (250 microM) and capric acid (250 microM, 500 microM). The fatty acids may influence neuronal excitability, in part, through a direct membrane action. The observed synaptic enhancement is consistent with a role for a fatty acid in long-term potentiation. In addition, fatty acid exposure mimics the effects of X-radiation. We suggest that free radical-induced release of fatty acids contributes to electrophysiological damage in a number of pathological states. PMID- 1762680 TI - Autoradiographic localization of dopamine D1 and D2 receptors in rat nucleus accumbens: resistance to differential rearing conditions. AB - The radioligands [3H]SCH 23390 and [3H]spiroperidol were used to label dopamine D1 and D2 receptors, respectively, in rat brain slices. Striatal sections were incubated in one of various concentrations of radioligand in the presence or absence of (+)-butaclamol and the resulting labeling was determined by liquid scintillation spectrometry. Scatchard analyses of the data revealed KD values of 1.18 nM for D1 receptors and 0.33 nM for D2 receptors. Tissue sections taken from the entire rostrocaudal extent of the nucleus accumbens, as well as other brain regions, were then processed for autoradiographic analysis of D1 and D2 receptors using a radioligand concentration equal to 1.5 X KD. After apposing the slices to 3H-sensitive film, topographical differences among brain areas were analysed using a quantitative densitometry system which determined the absolute amount of ligand binding relative to calibrated optical density standards. The nucleus accumbens exhibited a rostral-to-caudal density gradient for both D1 and D2 receptors. For D1 receptors, the density was similar across most of the nucleus accumbens, although the most caudal portion examined had a lower density than rostral portions. In contrast, the density of D2 receptors exhibited a more gradual gradient across the entire rostrocaudal extent of the nucleus accumbens. There was no significant rostrocaudal density gradient of either D1 or D2 receptors in either the olfactory tubercle or caudate-putamen in the same tissue sections. A lateral-to-medial gradient of D2 receptors was also present in the nucleus accumbens. That is, while there was no difference in the density of D1 receptors between the lateral core and medial shell subdivisions, the shell had a lower density of D2 receptors than did the core. The density of D1 and D2 receptors in the mesolimbic and nigrostriatal systems was compared in groups of animals raised from 30 to 60 days of age in an impoverished condition, a group caged condition or an enriched condition. While the brain weight of enriched condition animals was higher than impoverished condition animals, there were no significant differences in the density of D1 or D2 receptors among the different groups. Apparently, the densities of D1 and D2 receptors in the brain are resistant to differential rearing conditions. PMID- 1762681 TI - Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced injury of dopaminergic nigrostriatal system on movement components of the instrumental reflex and motor thalamic neurons' reactions in the cat. AB - Peculiarities of excitation and inhibition in ventral lateral and ventral anterior thalamic neurons were studied in cats with movement disorders (bradykinesia and muscle rigidity) induced by injury of nigrostriatal dopaminergic neurons with neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5 mg/kg daily, intramuscularly for five days). As was shown in chronic experiments, mean discharge frequency of neurons related to initiation of upper limb movements increased. Excitation of these neurons coincided with movement initiation, flexion and extension becoming more prominent and prolonged as compared with normal animals. In parallel to those changes, bradykinesia developed. In acute experiments performed under ketalar anaesthesia and myorelaxine immobilization it was found that neurotoxin caused a decrease of the inhibition duration and effectiveness in relay and non-relay thalamic motor nuclei neurons. The inhibition deficiency was accompanied by a shortening of latencies of orthodromic responses evoked by red nucleus stimulation. Two days after the last neurotoxin injection, light microscope examination revealed that about 48% of neurons located in the pars compacta of substantia nigra were destroyed. Electron microscopic analysis showed hydropic changes in perykaria and dendrites in most neurons of the substantia nigra pars compacta that are typical of the light type of degeneration. Pathomorphological processes in the synaptic apparatus were also found. The content of dopamine in the caudate nucleus fell to 30% as compared with intact animals. The suggestion is made that the deficiency of inhibition developed in motor thalamic neurons in response to nigrostriatal system destruction results from attenuation of dopamine-modulated direct GABAergic nigrothalamic influences and/or might be connected with increased inhibition of inhibitory interneurons of the same thalamic nuclei conditioned by pallidum disinhibition. PMID- 1762682 TI - Immunoelectron microscopic analysis of the synaptic connectivity of serotoninergic neurons grafted to the 5,7-dihydroxytryptamine-lesioned rat spinal cord. AB - The connections between the host and 5-hydroxytryptamine-containing neurons grafted to the spinal cord have been analysed using electron microscopic immunohistochemistry. Adult rats with 5,7-dihydroxytryptamine lesions of the brain and spinal cord received implants of embryonic medullary raphe neurons at three sites in the spinal cord. Eight to 10 months after grafting, the transplanted 5-hydroxytryptamine-positive neurons had formed extensive and complex contacts with spines, dendrites, perikarya and vesicle-containing structures in both the dorsal and ventral horns. Reinnervation of laminae IV-VI was less rich. In the graft itself, connections were also made between non immunoreactive varicosities and 5-hydroxytryptamine-containing dendrites, and somata, but the exact origin of the afferents was not determined. Outside the implant site, no obvious synaptic junctions onto grafted 5-hydroxytryptamine immunoreactive boutons were obvious, although labelled and unlabelled varicosities were often in close apposition. Synaptic junctions in the dorsal horn were predominantly symmetric, with the presynaptic varicosity containing mostly small agranular vesicles. By contrast, in the ventral horn most junctions were asymmetric, while the presynaptic element contained both small agranular and large dense-core vesicles. The results demonstrate that the types of synaptic contacts formed between the grafted 5-hydroxytryptamine neurons and the host spinal cord are remarkably similar to those found in intact spinal cord. In addition, the division of morphological differences that exists between 5 hydroxytryptamine-containing boutons in the normal dorsal vs ventral horns is also apparent in the transplanted animals. Finally, there appear to be present several anatomical substrates for the regulation by the host of 5 hydroxytryptamine output from the grafted neurons. PMID- 1762683 TI - A comparison of D1 receptor binding and mRNA in rat brain using receptor autoradiographic and in situ hybridization techniques. AB - D1, a subtype of the dopamine receptors, is widely distributed in the nervous system and has been shown to be positively coupled to adenylate cyclase. Using a combination of in vitro receptor autoradiographic and in situ hybridization techniques, the present study examines the co-distribution of D1 receptor binding sites and D1 receptor messenger RNA in adjacent rat brain sections. D1 receptor binding sites were labeled using the selective antagonist [3H]SCH23390 (4.6 nM) in the presence of 1 microM ketanserin, while the D1 receptor messenger RNA was visualized with a 35S-labeled riboprobe corresponding to a region between transmembrane domains III and VI of the rat D1 receptor (bp 383-843). Analysis of serial sections suggested a good agreement between D1 receptor binding and messenger RNA in several brain regions, including the paleocortex, caudate putamen, nucleus accumbens, amygdala and suprachiasmatic nucleus. Marked discrepancies between D1 receptor binding and messenger RNA were observed in other brain regions including the entopeduncular and subthalamic nuclei, substantia nigra (pars reticulata), hippocampus and cerebellum. While technical considerations may contribute to these results, much of the discordance between the distributions is likely due to the differential localization D1 receptor messenger RNA in cell bodies and receptor binding sites on fibers and may provide insights into receptor synthesis, transport and membrane insertion. In the basal ganglia, for instance, D1 receptors are synthesized in the striatum and are either transported to efferent projections in areas such as the substantia nigra, or remain localized in striatal cells bodies. Ibotenic acid lesions in the striatum are consistent with these conclusions and demonstrate a coordinate loss of D1 receptor binding and messenger RNA in the caudate-putamen that is accompanied by a degeneration of fibers projecting to substantia nigra and a loss of D1 binding in the pars reticulata. Neurons in the dentate gyrus and in the granular layer of the cerebellum, on the other hand, synthesize D1 receptors and transport them entirely to either their dendritic or axonal fields, respectively, in the molecular layer. This analysis provides a better understanding of dopaminergic receptor systems in the CNS and their anatomical organization. PMID- 1762684 TI - Chronic ascorbate potentiates the effects of chronic haloperidol on behavioral supersensitivity but not D2 dopamine receptor binding. AB - Ample behavioral evidence suggests that ascorbate parallels the action of haloperidol, a widely used neuroleptic. To determine the extent to which this parallel extends to chronic treatment, 21 days of exposure to ascorbate (100 or 500 mg/kg) alone or combined with haloperidol (0.5 mg/kg) were assessed on stereotyped behavior and neostriatal D2 dopamine receptor binding in rats. Our results indicate that when challenged with the dopamine agonist, apomorphine (0.5 mg/kg), animals chronically treated with haloperidol or high-dose ascorbate alone display a supersensitive sniffing response relative to controls, while animals chronically treated with the combination of haloperidol and high-dose ascorbate display a further potentiation of sniffing relative to the haloperidol groups. In addition, [3H]spiperone saturation studies showed, as expected, an up-regulation of striatal D2 dopamine receptors in rats treated with haloperidol as reflected by a change in receptor density (Bmax) but not affinity (KD). Ascorbate treatment, however, had no effect on D2 receptor density or the distribution of [3H]apomorphine in whole brain. Even though chronic treatment with the haloperidol-high-dose-ascorbate combination produced an up-regulation of striatal D2 dopamine receptors, this treatment did not cause a further up-regulation relative to haloperidol alone nor did it have any effect on [3H]apomorphine distribution. Taken together, these findings indicate that although chronic ascorbate produces behavioral supersensitivity to apomorphine through central mechanisms, they appear to differ from those induced by chronic haloperidol. PMID- 1762685 TI - Development of the endopiriform nucleus and the claustrum in the rat brain. AB - Long-survival [3H]thymidine autoradiography was used to quantitatively determine the time of origin of neurons in the endopiriform nucleus and the claustrum in rats killed on postnatal day 60 after their dams received two consecutive daily injections of [3H]thymidine on embryonic day E13 and E14, E14 and E15, ... E21 and E22. The claustrum originates late, on E15 and E16, and has a strong gradient in the longitudinal direction, posterior (older) to anterior (younger). In contrast, the endopiriform nucleus originates early, on E14 and E15, and lacks a longitudinal gradient but has a strong one in the vertical direction, ventral (older) to dorsal (younger). Sequential-survival [3H]thymidine autoradiography was used to qualitatively determine the germinal sources and settling sites of endopiriform and claustral neurons in embryonic rats. The dams received a single injection of [3H]thymidine on either E14 (to heavily label older endopiriform neurons) or E16 (to heavily label younger claustral neurons) and were killed in sequential 24-h intervals. Neurons in the presumptive endopiriform nucleus settle within two to three days after their peak time of neurogenesis while those in the presumptive claustrum take approximately five days to settle after their peak. It is postulated that endopiriform neurons are generated in the palliostriatal ventricular angle, the neuroepithelium that forms a wedge between the primordia of the neocortex and the basal ganglia, and that claustral neurons are generated in the neocortical neuroepithelium. Divergent developmental patterns between the endopiriform nucleus and the claustrum support the anatomical evidence that these nuclei have different connections. Furthermore, neurogenetic gradients in the claustrum correlate with the pattern of anatomical connections between the claustrum and the neocortex. PMID- 1762686 TI - Expression of c-JUN, JUN B and JUN D proteins in rat nervous system following transection of vagus nerve and cervical sympathetic trunk. AB - Expression of c-JUN, JUN B and JUN D proteins was investigated in axotomized neurons following transection of the vagus nerve and the cervical sympathetic trunk in the rat. Vagotomy induced the expression of c-JUN and JUN D in the nodose ganglion, dorsal motor nucleus of the vagus nerve and nucleus ambiguus, whereas JUN B was not expressed in these areas, c-JUN and JUN D appeared after 10 h in the nodose ganglion and after 24 h in the dorsal motor nucleus of the vagus nerve with a maximum of immunoreactivity after 48 h. The c-JUN protein remained expressed at an increased level up to 100 days, whereas the immunoreactivity of JUN D declined after five days. Crush of the vagus nerve initially evoked an intense expression of c-JUN and JUN D, but in the course of regeneration the expression of c-JUN and JUN D had returned to more basal levels after 100 days. Similar to vagotomy, application of colchicine and vinblastine on to the intact vagus nerve induced expression of c-JUN and JUN D. On the other hand, application of lidocaine prior to vagotomy did not prevent the expression of these proteins. Transection of the cervical sympathetic trunk induced expression of c-JUN and JUN D, but not of JUN B, in the preganglionic sympathetic neurons of thoracic spinal cord. In these neurons, expression of c-JUN was still enhanced after 60 days whereas JUN D had returned to basal level. One hour after vagotomy, c-JUN and JUN B were transynaptically expressed in the area of central termination of sensory vagal neurons and declined within 10 h to basal levels. JUN D showed a late onset of expression, it appeared after 5 h and persisted for 60 days in this area. We postulate that the expression of c-JUN and JUN D in axotomized neurons is induced by deprivation of a target-derived suppressor. PMID- 1762687 TI - Identification of a new non-neuronal cell type in rat olfactory epithelium. AB - We have examined adult and embryonic rat olfactory epithelia by immunohistochemical techniques using the monoclonal antibody 1A-6, which was raised against embryonic rat olfactory epithelia. A heretofore unidentified cell type, reactive with the monoclonal antibody 1A-6, was observed scattered within the epithelium. The 1A-6 reactivity of these cells is most intense on the microvilli projecting from the luminal cell surfaces. For several reasons, we believe these cells are not neurons but a distinct subpopulation of supporting cells or some other sort of non-neuronal cells. (1) They have no identifiable axonal process, are not reactive with an antibody against olfactory marker protein, and are not in juxtaposition with trigeminal axons. (2) They survive ablation of the olfactory bulb. (3) Their nuclei lie within the supporting cell layer, and they resemble supporting cells morphologically and in their [3H]thymidine birthdating and turnover characteristics. However, the 1A-6 positive cells fail to react with the general supporting cell-specific monoclonal antibody SUS-1 [see Hempstead J. L. and Morgan J. I. (1983) Brain Res. 188, 289 295] a finding which suggests that they are not typical supporting cells. Immunoreactivity to 1A-6 is developmentally regulated. Immunohistochemical preparations of almost all tissues we examined showed widespread reactivity in the embryo but a much more restricted pattern in the adult. In the olfactory epithelium of the fetus, the luminal surfaces of all cells, including supporting cells and olfactory receptor cells and cilia, are reactive, while in the adult only the non-neuronal cell subpopulation shows this reactivity. We also found that during the reconstitution of olfactory epithelium which occurs in response to olfactory bulbectomy-induced neuronal degeneration, fetal patterns of 1A-6 reactivity are not re-expressed, i.e. the only 1A-6-positive cells are the non neuronal cells seen in unperturbed adult olfactory epithelium. Preliminary biochemical analyses of membrane fractions from E19 brain and from adult olfactory mucosa indicate that the 1A-6 reactivity is associated with two bands, having molecular weights of 42,000 and 46,000 on Western blots. PMID- 1762688 TI - A morphometric evaluation of the effects of trichloroethylene and dichloroacetylene on the rat mental nerve. Preliminary results. AB - Morphometric analysis was used to compare the effects of trichloroethylene (Tri) and dichloroacetylene (Dca) on the fibre parameters of the trigeminal nerve. Treated animals were clearly separated from controls according to a discriminant analysis. Furthermore, in the class of nerve fibres defined by a clustering analysis and corresponding to the largest fibres, myelin thickness was significantly decreased in the Dca group, but less so in the Tri group. In the group of the smallest fibres however, the myelin thickness was significantly increased by the treatments, but especially by Tri. Such a variability in the effects of Tri has already been demonstrated. Mechanisms for this are quite unclear although demyelination could be involved as already suggested. Our results thus show the ability of Tri and Dca to alter nerve parameters but probably with different modes of action depending on the size of the fibre. PMID- 1762689 TI - Arachidonic acid metabolism in cultured astrocytes: presence of 12-lipoxygenase activity in the intact cells. AB - In our previous study, it was revealed that the exogenous arachidonic acid is mainly metabolized by the lipoxygenase pathway in the cell-free homogenate of cultured astrocytes. This is apparently in contrast with other studies reporting production and release of the cyclooxygenase products (prostaglandins and thromboxanes) by cultured astrocytes. To help specify the reason for this discrepancy, the metabolism of endogenous arachidonic acid in the intact monolayer of cultured astrocytes was examined. When the astrocytes were stimulated with calcium ionophore A23187, a peak coeluted with authentic 12 hydroxyeicosatetraenoic acid (12-HETE) on reverse-phase high-performance liquid chromatography (RP-HPLC) was observed. Formation of this peak was not affected by indomethacin, a speciic inhibitor for cyclooxygenase, but completely inhibited by BW755C, an inhibitor for both cyclooxygenase and lipooxygenases. Furthermore, the ultraviolet spectrum of the substance giving this peak agreed well with that of authentic 12-HETE. The amount of 12-HETE formed and released by the astrocytes was estimated to be 293.1 ng/mg protein/1 h. Taken together, these results suggest that the endogenous arachidonic acid is mainly metabolized by 12 lipoxygenase in the intact monolayer of astrocytes. PMID- 1762690 TI - Rapid interaction of tetraethylammonium with delayed K+ channel in mammalian brain neuron. AB - In order to study the rapidity of interaction between tetraethylammonium (TEA) and the delayed K+ channel of the mammalian brain neuron, TEA was applied to isolated rat hippocampal pyramidal neurons in a time-controlled sequence with a voltage step using a concentration clamp technique. TEA at a concentration of 30 mM, externally applied, started to decrease the delayed K+ current (IKD) without any detectable delay after the onset of the drug application. The inhibitory action of TEA reached a steady state within 10 ms while the full recovery from the inhibition required 20-30 ms after removing TEA from the external solution. Ba2+ at a concentration of 30 mM also reduced the IKD without any detectable delay. However, it took 40-60 s to reach the steady state of inhibition. Full recovery from the inhibition by Ba2+ was obtained around 60 s after removal of Ba2+ from the external solution. It is suggested that the interaction of TEA with the delayed K+ channel is much faster than that of Ba2+. PMID- 1762691 TI - Transient forebrain ischemia of three-minute duration consistently induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil. AB - We examined the effect of transient forebrain ischemia of 2-, 3-, 4- and 5-min duration on the development of delayed neuronal death in field CA1 of the hippocampus in the gerbil whose brain temperature was maintained at 37 degrees C. Transient ischemia of 3- and 4-min duration caused almost the same maximal damage in field CA1 as observed in the gerbils subjected to 5-min ischemia. A detrimental factor inducing delayed neuronal death in field CA1 may be already set up during the first 3 min after the onset of ischemia in the gerbil whose brain temperature is maintained at normothermic levels. PMID- 1762692 TI - Effect of bright light in the morning on diurnal variations of pineal indoles in NZBWF1 mice. AB - Exposure to bright light (2000 lx) for 2 h at the beginning of a 12 h light period (10 lx) resulted in about 1 h advances in the onset and termination of N acetylserotonin (NAc5HT) synthesis in the pineal gland of NZBWF1 strain mice compared with those in mice not exposed to bright light. These effects are in contrast with the effect of exposure to bright light throughout the light period, which delayed the onset of pineal NAc5HT synthesis in NZB mice. The possible relationship of these effects with the mechanism of action of phototherapy of human affective disorder is discussed. PMID- 1762693 TI - Production of an antiserum using a fusion protein produced by a cDNA for rat choline acetyltransferase. AB - A fusion protein produced by a cDNA for rat choline acetyltransferase (ChAT) inserted into a translation vector was used for immunization of rabbits. An antiserum was obtained that could recognize a single protein band in immunoblot analysis of a partially purified enzyme preparation of the rat brain. The antiserum revealed ChAT immunoreactivity in the motoneurons and terminal-like structures in the neuropil of the ventral horn in cryostat sections of the cervical spinal cord of the rat. This antiserum may be of particular use to study the development of the cholinergic neuron. PMID- 1762694 TI - Muscle inactivity reduces the content of parvalbumin in rat thymic myoid cells in vitro. AB - We investigated the influence of muscle inactivity by the addition of 1 microM tetrodotoxin in culture medium (complete abolishment of spontaneous firings); feeding with 50 mM KCl in the culture medium (inactivation of action potentials by depolarization) and the addition of 50 microM dantrolene sodium in culture medium (excitation-contraction uncoupling) on the content of parvalbumin in a cultured rat thymic myoid cell line (R615B2: M cells) using a highly sensitive enzyme immunoassay for rat parvalbumin. This is the first report of the content of parvalbumin in thymic myoid cells. Our studies clearly show that the content of parvalbumin is significantly decreased in paralyzed M cells compared with controls which had continuous muscle contractions. It is strongly suggested that muscle contractile activity plays an important role on the expression of parvalbumin in thymic myoid cells. PMID- 1762695 TI - Alteration in hypothalamic monoamine metabolism of freely moving diabetic rat. AB - Changes in hypothalamic monoamine metabolism were investigated in freely moving streptozotocin (STZ)-induced diabetic rats by using in vivo microdialysis technique. Six weeks later, the animals were implanted with microdialysis probe (molecular weight cut-off index: 12,000-14,000) into the ventromedial portion of the hypothalamus (VMH). The dialysate was collected and loaded onto HPLC to be assayed for norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites (MHPG, DOPAC and 5-HIAA). The concentration of NE was decreased in the dialysate from the VMH of diabetic rats, whereas there was no significant change in MHPG level. The concentrations of 5-HT and 5-HIAA were reduced in diabetic rats. The DA concentration was obviously increased accompanied by the reduction of DOPAC level. The observed changes in hypothalamic monoamine metabolism, especially the reduced NE release, may play an important role in the induction of hyperphagia in freely moving STZ-induced diabetic rats. PMID- 1762696 TI - Spectrin breakdown products increase with age in telencephalon of mouse brain. AB - Calcium activated proteolysis of brain spectrin produces characteristic breakdown products (BDPs), the concentrations of which increase markedly in many instances of brain pathology. Results reported here indicate that levels of the BDPs rise with age (3-30 months) in the telencephalon but not in the hindbrain of Balb/c mice. These observations suggest that spectrin breakdown is a pathologic biochemical marker which increases with age in some but not all brain regions. PMID- 1762697 TI - Hoechst 33342 a suitable fluorescent marker for Schwann cells after transplantation in the mouse spinal cord. AB - Purified rat Schwann cells labeled with Hoechst 33342 were transplanted into a lysophosphatidyl choline induced myelin lesion of the adult shiverer mouse spinal cord. Remyelination by grafted Schwann cells within the lesion was evidenced by codetection of Hoechst labeled Schwann cells and P0 (peripheral myelin protein) immunolabeled myelin on serial cryostat sections and confirmed on adjacent sec ions by electron microscopy. These data show that the Hoechst-shiverer model is an excellent model which can be used in intraspinal transplantation of myelin forming cells to demonstrate the origin of the newly formed myelin. Using this model, we bring the unquestionable evidence that cultured Schwann cells are capable after transplantation to participate with host oligodendrocytes in repair of a myelin lesion of the central nervous system. PMID- 1762698 TI - Carbachol-phorbol ester interactions at muscarinic receptors modulating dopamine release from rabbit striatal slices. AB - Both 4-beta-12,13-dibutyrate phorbol-ester (PDBu) (EC50% = 82 +/- 12 nM) and carbachol (EC50% = 2.3 +/- 0.3.5 microM) enhanced dopamine (DA) release from rabbit striatal slices. No additivity was observed when slices were treated simultaneously with 0.1 microM PDBu and 10 microM carbachol. Pretreatment with PDBu (0.01-0.1 microM) abolished carbachol-induced facilitation of DA release. Pretreatment with carbachol (3-100 microM) antagonized the enhancement in DA release produced by PDBu. The effect of carbachol was blocked by atropine (0.1 microM) and not by hexamethonium (10 microM). The effect of PDBu was not modified by the acetylcholine receptor (AChR) antagonists. If muscarinic (MAChR) MAChR were blocked by atropine (0.1 microM), pretreatment with carbachol failed to antagonize PDBu-induced facilitation of DA release. This is the first report to indicate that activation of M1-MAChR by an agonist prevents the effects of an active phorbol-ester. We suggest that activation of M1-MAChR enhances DA release possibly through activation of PKC. PMID- 1762699 TI - Effect of amygdaloid kindling on the high- and low-affinity [3H]TCP binding sites of the rat CNS. AB - The regulation of the binding sites of [3H]TCP, a non-competitive ligand of the N methyl-D-aspartate (NMDA) receptor, was studied on membranes prepared from different CNS regions of amygdaloid-kindled rats. The high-affinity binding sites (KdH = 4.2-7.4 nM), identified as the NMDA-gated ion channels, were not affected by kindling or by a daily injection of TCP (5 mg/kg before each electrical stimulation) which prevented kindling. These results suggest that the NMDA receptors participate to the establishment and not to the permanence of kindling. Kindling increases the number of low affinity [3H]TCP binding sites in the hippocampus (+21%, P less than 0.01) without change of the affinity (KdL = 340 nM). In the striatum both KdL and BmaxL were increased (3.3-4.4 fold, P less than 0.001) in animals pretreated with TCP before each electrical stimulation for 20 days. These last results argue in favour of a function of the low-affinity [3H]TCP binding sites, the nature of which remains to be determined. PMID- 1762700 TI - Inhibitory action of acetylcholine, baclofen and GTP-gamma-S on calcium channels in adult rat sensory neurons. AB - High- and low-voltage activated calcium channel currents (HVA and LVA) were inhibited by acetylcholine (10-100 microM) and baclofen (10 microM) in adult rat sensory neurons. This modulatory effect was present on dihydropyridine (nifedipine 1 microM) and/or omega-conotoxin (3.2 microM, 2-5 h incubation) insensitive components and was insensitive to holding potentials (Vh -50 to -90 mV). GTP-gamma-S (100 microM) prolonged calcium channel current activation in a time- and voltage-dependent manner. On the other hand, the current amplitude reduction induced by muscarinic and GABAB receptor activation, was not relieved by a 50-ms conditioning prepulse to +50 mV. This suggests the possibility of an alternative voltage-independent modulation mechanism. PMID- 1762701 TI - Battery burn. PMID- 1762702 TI - Fighting AIDS. PMID- 1762703 TI - What about Halcion? AB - Although Halcion has received a great deal of attention and scrutiny, Halcion and the other benzodiazepines have a place in the pharmacotherapy of anxiety, panic, and sleep disturbances. Obviously, any physician's prescribing practices are going to be influenced by a variety of factors, including the popular press, to some extent. However, by paying careful attention to prudent and appropriate prescribing practices, following indications and guidelines for safety, efficacy, and patient acceptance, and by prescribing Halcion with the same cautions one would prescribe any other short-acting benzodiazepine or other hypnotic, this medication can be safe, efficacious, and a useful adjunct to the treatment of insomnia. Side effects--even such rare ones as musical hallucinations--will occur, to a greater or lesser extent, as with any medication, but these can be managed by the prudent physician, taking into account the risk/benefit considerations of Halcion, or any benzodiazepine, as a physician would in prescribing any medication for any reason. PMID- 1762704 TI - A time for coming together. PMID- 1762705 TI - Advance directives for health care: clinical implications. AB - With the passage of new legislation concerning living wills, or advance directives for health care, the MSNJ Committee on Biomedical Ethics offers its resources to the physicians of the state including distribution of educational material and provision of sample advance directive forms. PMID- 1762706 TI - Oncogene probes in the diagnosis of malignant lymphoma. AB - The authors discuss the utility of oncogene probes to differentiate a case of follicular non-Hodgkin's lymphoma from follicular lymphoid hyperplasia. The case report concerns a 50-year-old white male; physical examination revealed generalized, marked lymphadenopathy. PMID- 1762707 TI - Musical hallucinations and triazolam use. AB - Musical hallucinations developed in a healthy 57-year-old man after using hypnotic triazolam (Halcion) for eight nights; the hallucinations continued for over one year. Although a causal relationship to triazolam cannot be proved, use of this drug has been associated with other bizarre alterations of memory. PMID- 1762708 TI - Ethical aspects of oncologic practice. AB - Oncologists must consider the ethical implications of all of their efforts. The patient's welfare and the likelihood of benefit from each therapeutic maneuver should be primary concerns. The author presents a set of general principles and guidelines for the care of cancer patients and others with incurable diseases. PMID- 1762709 TI - Colonic necrosis in the hemolytic uremic syndrome. AB - A previously healthy 14-year-old male survived extensive colon resection and ileostomy for acute colonic necrosis. The diagnosis of hemolytic uremic syndrome was made and intensive postoperative care was required. He made a complete recovery. PMID- 1762710 TI - The founding of the MSNJ Auxiliary. AB - The MSNJ Auxiliary was founded on June 7, 1927. Mrs. Miriam Lee Lippincott served as its first president and guided the Auxiliary in its early years. Mrs. Lippincott's medical contributions are outstanding. The MSNJ Auxiliary soon will celebrate 65 years of service to the medical community. PMID- 1762711 TI - A case for inservice education. PMID- 1762712 TI - Democracy at work. PMID- 1762713 TI - Nursing education: where do we go now? PMID- 1762714 TI - Hydration & ageing. PMID- 1762715 TI - Quenching thirst. PMID- 1762716 TI - Off her file! PMID- 1762717 TI - Proud of its involvement: Manawatu Polytechnic's role in the development of care giver courses. PMID- 1762718 TI - The right to speak out. PMID- 1762719 TI - Cup/disk ratio in branch retinal vein occlusion. AB - Recent reports have been attempted to evaluate, without obtaining a positive result, whether the reduction in size of the optic disc may influence the pathogenesis of central retinal vein occlusion. Cup/disc ratios in the fellow eye of 67 patients with branch retinal vein occlusion were compared with the ratios of 67 controls matched to cases for age, sex and refractive defect. There was no significant difference between cup/disc ratios of the two groups. These results suggest that the anatomical features of the optic disc are of no importance in the development of branch retinal vein occlusion. PMID- 1762720 TI - Ophthalmic complications in patients with paranasal sinus mucopyoceles. AB - We examined 45 (23 male and 22 female) Japanese patients with paranasal sinus mucopyoceles associated with ophthalmic complications. The patients ranged in age from 31 to 87 years. The patient distribution by the affected sinus was as follows: maxillary sinus alone, 17 patients; ethmoidal sinus alone, 9 patients; frontoethmoidal sinuses, 9 patients; frontal sinus alone, 7 patients, and other multiple sinuses, 3 patients. Thirty-nine mucoceles and 6 pyoceles were identified. Ophthalmic signs and symptoms included lid swelling, ocular pain, pseudoptosis, proptosis, displacement of the eyeball, epiphora, slight blurring of vision, severely decreased visual acuity, visual field abnormality, diplopia, disk edema, retinoichoroidal folds and increased intraocular pressure. Of the 45 patients, 1 had a history of sinus trauma and 29 had a history of sinus surgery. PMID- 1762721 TI - Orbital tumor in an infant with acute monocytic leukemia associated with chromosome 5q-,t(9p-11q+),11p+. AB - We examined an 8-month-old infant with left proptosis, chemosis and orbital mass. A computed tomographic scan revealed a left orbital tumor. An anorectal nodule was also found. Results of the hematologic study showed poorly differentiated acute monocytic leukemia (M5 according to the French-American-British classification). Chromosomal analysis disclosed 46, XX,5q-,t(9p-;11q+),11p+. We believe that our patient represents a rare case of orbital tumor in acute monocytic leukemia associated with chromosomal abnormalities. PMID- 1762722 TI - Optic nerve hypoplasia associated with porencephalia in a girl and retinitis pigmentosa in her sister. AB - An 18-year-old women (case II-4) had decreased visual acuity, visual-field defects and small optic disks bilaterally that remained unchanged for a follow-up period of 9 years. The patient also had an abnormal cavity within the cerebral hemispheres. Her 29-year-old sister (case II-1) had night blindness, bone corpuscle pigmentation in mottled retinas and nonrecordable electroretinographic responses bilaterally. We believe that the occurrence of optic nerve hypoplasia associated with porencephalia in one patient and retinitis pigmentosa in her eldest sister may be rare. PMID- 1762723 TI - Effects of ionizing radiation on human conjunctival epithelial cells: a clinical and cytologic study. AB - In order to identify early and late modifications induced by ionizing radiation on the conjunctival surface, we studied 10 patients irradiated for paranasal sinus tumors. A clinical and morphological study of conjunctival epithelium (using an impression cytology technique) was performed; 5 patients were examined during and the others after treatment. Actinic conjunctivitis and keratitis, observed during treatment, reappeared within a few months after the end of radiotherapy. At a threshold dose of 25 Gy, chronic nuclear changes and cellular surface disorganization of the conjunctival epithelium were found--these progressed and persisted. Our data support the importance of careful monitoring of such irradiated patients and the benefit of planning a prospective clinical study to evaluate the effects of available drugs (all-trans retinoic acid) in the treatment of these lesions. PMID- 1762724 TI - Retinal early receptor potential in retinitis pigmentosa: correlations with visual field and fluorangiography estimates. AB - The flash induced electroretinogram (ERG) and early receptor potential (ERP) were recorded in a population of patients with definite diagnosis of retinitis pigmentosa in the context of a study protocol including a complete diagnostic screening. ERPs were evoked by full-field 20-joule stimuli (5 stimuli at 10 min of interval in dark adaptation); recording was by skin electrodes positioned at the inferior orbital margin; amplifiers were set at 10-10,000 Hz. The flash ERG was absent or markedly abnormal in all cases, even at an early stage of development of the retinitis, while ERPs (with a normal morphology, latency of the R1 component increased and a reduced amplitude compared to normal controls) could be identified unambiguously in all cases. The amplitude reduction was highly correlated with the severity of the disease as determined by kinetic perimetry and fluorangiography. PMID- 1762725 TI - Electrophysiological findings in peripheral uveitis. AB - Nine patients with peripheral uveitis were studied clinically and electrophysiologically. Electroretinographic findings varied widely from supernormal to nonrecordable responses, depending on the disease duration and severity. These results suggest that the pathology in peripheral uveitis is not necessarily limited to the inferior pars plana but can be diffuse and widespread. In the final stage of the disease, the fundus showed extensive pigmentation and narrow retinal arteries associated with a nonrecordable electroretinogram, similar to retinitis pigmentosa. Burned-out peripheral uveitis should be considered in the differential diagnosis of secondary pigmentary degeneration. PMID- 1762726 TI - Influence of amblyopia on high-pass resolution perimetry. AB - Seventeen subjects with amblyopia due to strabismus and anisometropia were examined using high-pass resolution perimetry. In addition to the standard technique, testing the 5-30 degrees visual field, an optional program testing the central 4 degrees visual field was used. Threshold elevation was confined to the central 4 degrees visual field and strongly correlated with visual acuity, expressed as minimum angle of resolution. Standard high-pass resolution perimetry did not reveal any significant abnormalities in the amblyopic subjects. In conclusion, the technique is useful for the diagnosis of ocular or neurologic disorders also in subjects with a high degree of amblyopia. PMID- 1762727 TI - [Current approaches to the development of a system of automated diagnosis of osteochondrodysplasias in children]. AB - On the basis of studying of data on 1469 patients there is proposed a methodology of development of a system of automated diagnosis of osteo-chondrodysplasia in children. It is based on registration of the course peculiarities, variety of clinical and genetic forms, inter- and intragroup similarity and progredient course of diseases of the type. At the first stage there have been made a complex analysis of formalized clinico-roentgenologic signs of osteo-chondrodysplasia with the aid of "Rbase-5000" program package. Osteo-chondrodysplasia course regularities, revealed in this way, were used further on in the process of an expert system development for their automated diagnosis. PMID- 1762728 TI - [Pathogenesis of stenosing ligamentitis]. AB - On the basis of complex examination of women with stenosing ligamentitis, including investigations of hormonal background in accordance with the clinical criteria, hormonal smears, radioimmunological assay of the initial vegetative tonicity, blood circulation by means of rheography, it has been concluded that the stenosing ligamentitis is the local expression of general dystrophy of the connective tissue due to hormonal shift, pathology of the vegetative nervous system and the circulatory system. PMID- 1762729 TI - [Comparative analysis of osteotomy methods in open setting of congenital hip dislocation in children]. AB - There is given an analysis of the treatment of 89 children (99 joints) with congenital femur dislocation, which were subjected to corrective osteotomy at the open setting by three different methods. There are shown the advantages of oblique osteotomy, proposed by the authors. There have been developed and substantiated the indications for application of oblique and transversal osteotomy of the femur. PMID- 1762730 TI - [Treatment of bilateral dysplastic instability of the hip joints]. AB - In the article are described the peculiarities of the treatment tactics and presented an integral assessment of treatment efficiency of 563 patients with bilateral dysplastic instability of the hip joints (bilateral dislocation, bilateral primary subluxation, dislocation of one and subluxation of the other joint), carried out in the hospital of the institute named after M. I. Sitenko in 1955-1989. There is noted a necessity of achievement of anatomo-functional symmetry of the hip joints as a strategic aim of treatment and an expediency of application of "anticipation estimate" principle while planning the treatment measures for these patients. PMID- 1762731 TI - [Rehabilitative therapy after correction of congenital clubfoot in children]. AB - There have been analysed 49 children with congenital club foot (79 feet). All patients before arrival were treated according to the common methods and 42 children (64 articulations) were subjected to operative or apparatus-made correction of the club foot recurrence. In spite of the treatment obtained all children arrived with the residual signs of club foot. There are described the mechanisms of the club foot recurrence development, proposed a method of stage-by stage redressment, needle and manual therapy realization. PMID- 1762732 TI - [Characteristics of foot blood supply in rigidity of the great toe]. AB - By means of angiography, made in 20 patients with rigidity of the first toes due to osteoarthrosis, there have been revealed chronic deficiency of blood circulation in the foot tissues, especially in its antero-internal section. Blood circulation deficiency is due either to the congenital anomaly of the foot vessels or to the consequences of their traumatic injuries. Blood supply deficiency results in degenerative-dystrophic changes of the first metatarsophalangeal articulations with development of their rigidity, aggravated by post-ischemic contracture of the foot muscles. PMID- 1762733 TI - [An echocardiographic study of the cardiovascular system in patients with kyphoscoliotic deformation of the spine in Marfan's syndrome]. AB - In the work are presented the results of echocardiographic investigation of 19 patients (aged 11-15) with kyphoscoliotic spine deformities at the Marfan's syndrome. The analysis of the obtained data has shown that the most common type of the cardiovascular system pathology in 78.9% of the examined children and adolescents was the II and III stage prolapse of the mitral valve. The changes of the heart cavity dimensions and the signs of the ventricle overloading have not been detected. Prolapse of the mitral valve cusps to the III stage was the most often accompanied by the root and aorta ascending section dilatation. The presence of the heart affection should be considered as one of the indications to carry out the corrective operations at the spine, allowing to reduce the heart overloading and decrease the probability and rate of progression of the cardiac disturbances, specific for this syndrome. PMID- 1762734 TI - [Effects of benzofurocaine, etaden and xanthinol nicotinate on reparative bone regeneration in animal experiments]. AB - In the process of treatment of experimental close fractures of radius in rats by intramuscular administration of benzofurocaine (60 mg/kg), the regeneration processes of the bone tissue were activated to a greater degree than in case of administration of etadene (20 mg/kg) or xanthinol nicotinate (30 mg/kg). Under the influence of benzofurocaine, beginning on the 10-20-th day of the experiment, there have been noted the reorganization of young callus into the mature laminal bone. The preparations of comparison have demonstrated less expressed analogous action. PMID- 1762735 TI - [Possibilities of prognostication of complications in long bone fractures]. PMID- 1762736 TI - [Some problems in the organization of medical aid in multiple and associated injuries]. AB - On the local material are considered the cases of multiple and associated trauma according to the information of surgical department of the central regional hospital, bureau of forensic medical examination and traffic inspection. The results of the associated trauma treatment can be improved by means of timely first aid rendering at the place of an accident, short-term delivery of a patient to the hospital, extensive application of laparocentesis, operative intervention during the first hours of delivery to the hospital as well as by improvement of the ambulance and hospital work, further firm establishment of the sober mode of life and rigorous and centralized registration of patients with polytrauma. PMID- 1762737 TI - [Treatment of patients with ununited fractures and pseudarthrosis of crus bones using G. A. Ilizarov's method]. PMID- 1762738 TI - [Rare forms of suppurative arthritis]. PMID- 1762739 TI - [Talus distractor]. PMID- 1762740 TI - [A device for performing of osteotomy and segmental resections of long bones]. PMID- 1762741 TI - [A method of anterior spondylodesis]. PMID- 1762742 TI - [Aplasia of the radius of the hand]. AB - In the article is described the congenital pathology of the hand, characterized by the absence of one or several fingers with the corresponding metacarpal bones and bones of the wrist. There is given the clinical picture of 104 patients with the hand radius aplasia. There are singled out main forms of pathology, presented the data of the additional investigation methods (angiography, rheovasography, histologic structure of the affected hand tissues). There are presented the main principles of the hand radius aplasia treatment. PMID- 1762743 TI - [A device for external fixation using hollow rods]. PMID- 1762744 TI - [A pivotal device for functional treatment of crus bone fractures]. PMID- 1762745 TI - [Rubber hinges in prostheses]. PMID- 1762746 TI - [Adaptive-compensatory changes in congenital disorders of the development of the locomotor system]. PMID- 1762747 TI - [Conceptual model of the pathogenesis of instability of the shoulder joint]. PMID- 1762748 TI - [Assessment of consolidation and temporary disability in fractures]. PMID- 1762749 TI - [Index of surgical activity (for purposes of discussion)]. PMID- 1762750 TI - [Life and activities of Fedor Rodionovich Bogdanov]. PMID- 1762751 TI - [Liver diseases and changes in the locomotor system]. PMID- 1762752 TI - [Several aspects of the surgical treatment of post-traumatic contractures and ankylosis of the elbow joint]. AB - The authors have studied the results of treatment of 52 patients with inveterate damages of the elbow joint and different function disturbances as well as looked for the best variants of the operative treatment of contractures and ankylosis. They have analysed the results of treatment of 39 patients with inveterate and incorrectly consolidated elbow joint fractures and dislocation fractures in the period of 6 months--4 years after the operation. Excellent results were noted in 9 patients, good in 13, satisfactory in 10 and unsatisfactory in 7 of them. Arthrolysis of the elbow joint in case of its inveterate damages is the method of choice. Arthroplasty is indicated in cast of fibro-osseous ankylosis, incorrectly consolidated fractures with the joint injury congruence disturbance, rheumatoid polyarthritis. The problem of control of cicatricial and commissural processes and development of heterotypic ossification is a very urgent one and requires special studying and working out of the control methods of these processes. PMID- 1762753 TI - [The significance of the dipyramidole echocardiography test in ischemic heart disease]. AB - The diagnostic value of the dipyridamole echocardiography test was investigated in 46 patients who underwent coronary angiography due to suspected ischaemic heart disease. Twenty-two of 46 patients were found to have a narrowing of at least 70% one vessel. Twenty-four hour ECG monitoring was also performed on 19 patients on the day of the dipyridamole test. The sensitivity and specificity of the two-dimensional echocardiography test (new wall motion abnormality) were 72.7% and 62.5%. The ECG (V2-5-9) had a low sensitivity during the test (43.8%). Good agreement was found between the localization of the wall motion abnormalities and the site of anatomic narrowing in the ischaemic group. No significant ventricular arrhythmias were detected, and the sensitivity and specificity of ST-T changes were found to be 62.5% and 54.6% by means of Holter monitoring. The dipyridamole echocardiography test proved to be a suitable noninvasive method for the diagnosis of ischaemic heart disease and for the selection of patients for coronary angiography. PMID- 1762754 TI - [Primary hemostasis in mixed connective tissue disease]. AB - Willebrand-factor antigen level and structure analysis, ristomycin-cofactor assay, beta-thromboglobulin and thromboxane metabolite estimations were performed in 22 patients with mixed connective tissue disease. High levels of Willebrand factor antigen and activity were detected in the presence of thrombocytopenia, previous thrombotic events, pulmonary vascular lesions and in the presence of circulating antiendothelial antibodies. Increased platelet activation was documented also in antibody positive cases and in thrombocytopenia. The alterations of endothelial and platelet functions may play important role in the development of vascular complications of mixed connective tissue disease. PMID- 1762755 TI - [Chromosome analysis in spontaneous abortion using direct preparation of chorionic villi]. AB - Two hundred cases of spontaneous abortions were studied by analysing chromosomes directly from chorionic villi. Abnormal karyotypes were found in 52% of the investigated cases. Among the chromosome abnormalities the most frequent were the trisomies (56.7%) followed by polyploidy (23.1%), monosomy X (15.4%) and structural anomalies (4.8%). The rapid and relatively simple method is suitable for studying the causes of spontaneous abortions, and these information may be helpful also for genetic counselling. PMID- 1762756 TI - [Osteitis pubis]. AB - Lytic degeneration of the pubic symphysis is a relatively rare entity. The present study is dedicated to the fact that the disease causes numerous diagnostic problems. Authors based on their three cases describe the clinical features and review the literature. It is stated that both from the aspect of the diagnosis and the result of the treatment, operative intervention is beneficial. In contraversion to numerous papers it is found that the described disease is often infectious and can be consequence of an infection of the urinary tract. PMID- 1762757 TI - [Idiopathic priapism in childhood]. AB - The authors described the operation technique of the spongiocavernosum shunt in connection with a successfully operated patient. In their case the Quackels procedure was applied with minor modifications, since the conservative one wasn't successful. Their patient is perfectly healthy functionally too. The etiologic factors could not be clarified. PMID- 1762758 TI - [Position of the presidency of the Allied Association of Hungarian Medical Societies (MOTESZ) on the "Action Program"]. PMID- 1762759 TI - [Search for human cancer genes]. PMID- 1762760 TI - [Current concept of autism]. AB - Childhood autism, the most characteristic subgroup of the broader PDD (pervasive developmental disorders) category, is the consequence of genetic or typically prenatal, organic factors causing cerebral damage. The resulting mental handicap lasts for a lifetime. It is characterized by a behavioural syndrome, that becomes recognizable between the 2.-3. year. The core of the syndrome is a deviant and/or retarded development of cognitive capacities and skills necessary for social relations, communication, fantasy and symbolic thinking. Almost all autistic people (95%) would not reach independence as adults, and most of them (75%) is mentally retarded as well. According to our calculations about 16,000 people are affected in Hungary, in a more or less serious degree, 2000 children among them. Their condition would require intensive, early and long lasting intervention: conditioning, training, education, and special social services. Today we do not possess the necessary organisational background, nor the professional training, and knowledge. For the early diagnosis, proper care and services the competence of child- and general psychiatrists, also of family doctors is indispensable. The author summarizes the most important available informations on the field first of all for those, who work in the general medical services. PMID- 1762761 TI - [The role of gastroesophageal reflux in the hemorrhaging of esophageal varices. Effect of endoscopic sclerotherapy]. AB - From January 1st to December 31st 1987, 51 prospectively selected patients underwent 24-hour intraesophageal pH monitoring before, and 5 weeks after endoscopic paravariceal sclerotherapy (ESCL). Patients were divided into two groups: in group I. first pH monitoring was done 24 hours after acute variceal bleeding; in group II. one month after a previous bleeding episode. Gastroesophageal reflux (GER) was expressed by percentage of time below pH 4, and by average number of reflux episodes, lasting longer than 5 seconds, per hour. In group I. the time below pH 4 (10.3 +/- 2.05%) and the number of reflux episodes (24.4 +/- 4.2/h) were significantly higher, than those in group II. (2.57 +/- 0.14%; 2.39 +/- 0.31/h). Pathologic GER parameters were significantly more frequent in group I. (50% and 73%), than in group II. (16.7% and 29.1%). ESCL significantly reduced GER in both groups of patients. In group I. GER remained pathologic at 12.5% and 20.8% of patients. In group II. time below pH 4 became normal at all of the patients, and only one of them has pathologic number of reflux episodes. Our data give evidence of GER having a possible causative role in initiating variceal bleeding. ESCL significantly reduces GER. This effect might contribute to long term results of ESCL. PMID- 1762762 TI - [Clinical usefulness of the dobutamine test in the diagnosis of coronary disease]. AB - In the diagnostics of the coronary artery disease different exercise tests are well-known to be important. On the basis of the increasing number of publications of the eighties the authors examined the applicability of dobutamin stress test in 89 patients, whose anamnesis did not contain any justification of coronary artery disease. All patients were examined by coronarography. The authors compared the results of different tests with the results of coronarography. They found the sensitivity of dobutamin stress test significantly higher and its specificity--although not significantly--lower, than the dynamic treadmill tests, however the combination of the two methods resulted in very good sensitivity and acceptable specificity. PMID- 1762763 TI - [Rare cases of primary hyperparathyroidism]. PMID- 1762764 TI - [Prinzmetal angina and syncope]. AB - Authors report an unusual case of variant angina associated with unconsciousness. They were able to prove by coronary angiography the vasospasm of the circumflexus artery which was responsible for the morning attacks of the 35 year old patient with unconsciousness, ST segment elevation and high degree AV block. Unconsciousness was the first and earliest sign of the coronary vasospasm. PMID- 1762766 TI - [Current facts on the care of stomas]. PMID- 1762767 TI - [Living with a stoma. Interview by Angelika Grimm]. PMID- 1762765 TI - [Effect of antioxidants on the oxidative stress of red blood cells]. AB - Antioxidant nomination covers a substance group of great variety, therefore, the determination of action mechanism of new antioxidants requires a complicated test system. The present work demonstrates this labour and time consuming procedure conducted on human red blood cells (RBCs) exposing them to "stress effect" with diluted hydrogen peroxide. It was studied how did these oxidative stress conditions affect the filtration parameters, lipid peroxidation, reduced glutathione content and superoxide dismutase activity of RBCs. It was attempted to reverse or influence the significant changes caused by "oxidative stress" with known antioxidants (vitamin E and uric acid). PMID- 1762768 TI - [Description of a profession: the stoma therapist]. PMID- 1762769 TI - [Because the large size is dangerous]. PMID- 1762771 TI - [The labyrinth]. PMID- 1762770 TI - ["Woe be to those who publicly censure physicians"]. PMID- 1762772 TI - The anatomy of the facial nerve. AB - The course of the facial nerve from its origin in the human brain-stem to the termination of its end fibers in the muscles of facial expression is reviewed in detail. The relation of the facial nerve to important adjacent structures is emphasized so that the aural surgeon is better prepared to explore in this intricate area. PMID- 1762773 TI - Management of facial nerve disorders. PMID- 1762774 TI - Surgical landmarks for the facial nerve. AB - A number of different approaches can be used to expose the facial nerve. The route taken will depend on the pathology and the portion of the nerve that requires exposure. When performing a parotidectomy approach to the extratemporal portion of the facial nerve, the tragal pointer is a key landmark, but other landmarks also should be used to identify the facial nerve safely. The lateral semicircular canal, the chorda tympani nerve, the digastric ridge, and the cochleariform process are some of the useful landmarks in the mastoid and middle ear. When performing a middle fossa approach, the superior semicircular canal, the greater petrosal nerve, and a window through the tegmen tympani into the attic are useful guideposts. The surgeon should use as many of the available landmarks as feasible to perform safe facial nerve surgery. PMID- 1762775 TI - Anatomic variations and anomalies involving the facial canal. AB - Congenital bony dehiscences in the facial canal result from incomplete closure during development and are observed in approximately 55% of temporal bones. Anomalies involving the facial canal frequently are encountered in malformations of the temporal bone. These anomalies include aberrations of the course of one or all of the segments of the canal; abnormal relation to the oval and round window; bifurcations and trifurcations of the nerve; and associations with dysplasia of the stapes, oval window, external ear canal, and auricle. Rarely, the facial nerve may be hypoplastic or totally absent. Two abnormal vessels occasionally may accompany the facial nerve in the Fallopian canal: a persistent stapedial artery and a persistent lateral capital vein. PMID- 1762776 TI - Testing facial nerve function. AB - A variety of facial nerve tests are now available. These tests can aid the clinician in discerning the site of lesion, estimating prognosis, assessing evidence of neoplastic or infectious involvement, and assisting in intraoperative facial monitoring. PMID- 1762777 TI - Facial nerve imaging. AB - A review of past, present, and potential future imaging of the facial nerve outlines the general technologic advances in radiology. The newer modalities provide more information than before; however, with more sophisticated technology, efficient use should be emphasized. A coordinated approach between the otolaryngologist and the radiologist is needed first to localize the most likely segment and then to perform a tailored radiographic study specifically for that segment. In this way, it is hoped that we can avoid unnecessary studies and achieve earlier diagnoses. PMID- 1762778 TI - Management of trauma of the facial nerve. AB - The general principles of management of trauma to the facial nerve from a variety of causes are presented and the indications for and timing of surgery are reviewed. Attention is given to management techniques unique to injuries of the extracranial, intratemporal, and intracranial divisions of the nerve. PMID- 1762779 TI - Differential diagnosis of facial nerve palsy. AB - The differential diagnosis of facial complex can be complex, but all efforts must be made to identify the cause so that appropriate treatment can be offered. This article presents a review of conditions associated with acute facial palsy and discusses the differential diagnosis of this condition. The focus is on the differentiation of other causes of acute facial palsy from the idiopathic, or Bell's type, which is a diagnosis of exclusion. PMID- 1762780 TI - Congenital and acquired facial nerve paralysis in children. AB - Facial nerve paralysis in children should be considered distinct from that which occurs in adults. The author submits a slightly different classification of facial nerve paralysis in children based on traditional thinking. Specifically, acquired facial nerve paralysis is thought to be influenced by both prenatal and postnatal factors. This segregated approach toward acquired paralysis should allow a clearer understanding of the pathophysiology of in utero factors. PMID- 1762781 TI - Management of the facial nerve in skull base surgery. AB - The facial nerve presents a significant obstacle to adequate surgical exposure of lesions involving the skull base. The evolution of various surgical approaches to the jugular foramen, petrous apex, and lateral facial approaches to the skull base aimed at preserving the seventh cranial nerve are reviewed. Methods and techniques in management of the intratemporal and extratemporal facial nerve are discussed. PMID- 1762782 TI - Medical management of idiopathic (Bell's) palsy. AB - Experience with treating more than 400 cases of Antoni's palsy, the findings of autoimmune reaction, and recent gadolinium-enhanced magnetic resonance imaging reports in "idiopathic" Bell's palsy verify the hypothesis that the disease results from a viral geniculate ganglionitis. The diagnosis no longer needs to be one of exclusion. We now are capable of establishing a positive diagnosis, permitting the clinician to initiate treatment with corticosteroids and acyclovir confidently. Facial nerve compression and electrotherapy are not advised. It is suggested that the term idiopathic Bell's palsy be replaced with Antoni's palsy as the first step in changing erroneous concepts of the past. PMID- 1762783 TI - Surgical decompression of idiopathic facial palsy. AB - There is no consensus on the cause of Bell's palsy, just as there is no proven medical therapy. Disregarding the numerous theoretic causes, preponderant anatomic, electrophysiologic, radiologic, clinical, and pathologic evidence supports entrapment at the medical foramen of the fallopian canal as a final common pathway resulting in facial nerve ischemia and degeneration. Middle cranial fossa decompression of the meatal foramen may benefit those patients most severely affected with Bell's palsy. PMID- 1762784 TI - Facial nerve grafting. AB - The techniques of facial nerve grafting have undergone several adjustments and refinements within the last 20 years. Those techniques that have stood the test of time are discussed, and new approaches to facial nerve grafting in the temporal bone are explored. PMID- 1762785 TI - Intraoperative facial nerve monitoring. AB - Facial nerve monitoring is one of the most exciting innovations in otologic surgery in the past decade. Intraoperative monitoring has been shown to reduce the probability of iatrogenic injury to the facial nerve during surgery. It saves surgical time and reduces the anxiety level of both patients and surgeons. There are several reasons to use facial nerve monitoring: The surgeon nerve knows when it will be needed in a particular case, the operating room personnel become familiar with the equipment, and the surgeon learns how to interpret the sounds produced by the monitor and how to correlate them with surgical manipulations around the facial nerve. Facial nerve monitoring has added another dimension of safety to otologic and neurotologic surgery and has reduced the incidence of facial weakness or paralysis in the authors' surgical practice. PMID- 1762786 TI - Rehabilitation of the paralyzed face. AB - Rehabilitation for facial paralysis is a highly individualized task that relies on a complex set of physical, physiologic, social, and emotional factors. A wide range of surgical techniques exist for establishing partial rehabilitation of facial expression and motion. The facial surgeon must analyze these factors and work with the patient in a realistic approach to the problem. PMID- 1762787 TI - Experimental nerve regeneration. A review. AB - The aim of peripheral nerve repair is to restore motor and sensory function, which requires more than just 10-0 sutures and a good microscope. The past decade has seen an explosion in the understanding of how nerves grow, and this information is being used to develop better treatments for nerve injuries. In the future, treatment will not be limited to the operating room, because postoperative adjuvant therapies will become increasingly more important in the management of nerve repairs. At the same time, advancement in manufacturing techniques, a better understanding of biomaterials, and the use of the laser will replace the time-honored techniques of surgical repair in many clinical settings. PMID- 1762788 TI - Cell and molecular anatomy of nicotinic acetylcholine receptor subunits and calcitonin gene-related peptide in the rat vestibular system. AB - In this report we demonstrate the pattern of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity in the central and peripheral vestibular system of the rat, using a CGRP cRNA probe and a polyclonal CGRP antiserum. We present evidence that somata in all regions of efferent vestibular neurons contain CGRP based on the correspondence between in situ hybridization (mRNA) and immunohistochemistry (mRNA translation product). CGRP immunohistochemistry (CGRPi) and in situ hybridization confirm that CGRPi axons and terminals present in the vestibular neuroepithelium are efferent in origin. Immunoelectron microscopy revealed an extensive innervation of the afferent vestibular pathway by CGRPi terminals that was not limited to the primary afferent chalice, as previously reported by Tanaka et al. (Brain Res 1989;504:31-5). An efferent neuromodulatory role of CGRP can be inferred from the distribution of terminals found on the primary afferent fibers, and type I and type II hair cells. In addition, we present evidence that nicotinic acetylcholine receptor (nAChR) subunit mRNA is expressed by primary afferent cell bodies. On the basis of these data, a hypothetical molecular mechanism of vestibular efferent modulation of the primary afferent pathway is proposed. PMID- 1762789 TI - The protective effects of tirilated mesylate (U74006F) on ischemic and reperfusion-induced cochlear damage. AB - We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia. PMID- 1762790 TI - Hierarchical immunosuppression of regional lymph nodes in patients with head and neck squamous cell carcinoma. AB - Patients with head and neck squamous cell carcinomas (HNSCCs) manifest defects in cell-mediated immune function. Previous studies in this laboratory have demonstrated regional alterations in the immunocompetence of draining lymph nodes (LNs) in HNSCC patients. In this investigation, we studied functional activity of lymphocytes from lymph nodes in different locations in the radical neck dissections (RNDs) from patients undergoing operations for HNSCC. Lymphocytes from nodes close to the primary tumor ("near" lymph nodes or NLN) exhibited a significant decrease in interleukin-2 (IL-2)-activated cytotoxicity when compared to lymphocyts from distant nodes ("far" lymph nodes or FLN). In addition, co culture experiments suggested the existence of a soluble regulatory factor, produced by lymph nodes, that inhibited the development of lymphokine-activated killer (LAK) cells in vitro. Further experiments with conditioned supernatants from the lymph node cells confirmed the presence of this soluble inhibitory factor. The inhibitory effect is significantly greater in NLNs than in FLNS. This hierarchical phenomenon suggests a regional network of immunosuppression in HNSCC patients. It is likely that tumor- and lymph node-induced suppression plays a role in limiting the efficacy of current immunotherapy protocols in human beings. A greater understanding of mechanisms of local inhibition of immune function will aid in improving adoptive immunotherapy for treatment of cancers in human beings. PMID- 1762791 TI - Direct electrical stimulation of the cochlear nucleus: surface vs. penetrating stimulation. AB - Prosthetic stimulation of the cochlear nucleus (CN) has been used for rehabilitation of profoundly deaf patients who are not suitable candidates for cochlear implants. The goal of this article was to assess the relative effectiveness of surface vs. penetrating stimulation of the CN. Electrophysiologic and autoradiographic measures were used to study central auditory system activation elicited by direct stimulation of the CN. Eighteen pigmented guinea pigs, divided into three groups, underwent acute implantation of bipolar electrodes in the CN. One group was not stimulated and acted as a control (n = 7). Electrodes were placed on the surface of the CN in one test group (n = 4) and within the CN in a second test group (n = 7). Thresholds for electrically evoked middle latency responses (EMLR) were determined and input/output (I/O) functions were obtained. The two test groups were then pulsed with [14C]-2 Deoxyglucose (2-DG) intramuscularly and stimulated for 1 hour with biphasic; charge-balanced pulses having a total duration of 400 microseconds, a repetition rate of 100/sec, and an amplitude of 200 microA. After stimulation, animals were killed and brains were harvested and prepared for autoradiography using standard techniques. Threshold current for EMLRs in the surface-stimulated group had a mean of 67.5 +/- 23.9 microA (range, 40 to 100 microA). Thresholds for in-depth stimulated group had a mean of 11.4 +/- 3.5 microA (range, 10 to 20 microA). The saturation level of the I/O function for the surface-stimulated group had a mean of 287.5 +/- 41.5 microA (range, 250 to 350 microA). The saturation level for the in-depth stimulated group had a mean of 192.9 +/- 49.5 mciroA (range, 100 to 250 microA). The dynamic range for the surface electrodes had a mean of 13.1 +/- 2.7 dB (range, 9.9 to 15.9 dB), whereas the dynamic range for the penetrating electrodes had a mean of 24.5 +/- 2.6 dB (range, 20 to 28.0 dB). Autoradiographs generated by CNS tissue from stimulated animals demonstrated no significant difference in metabolic activity of the CN between surface and in-depth stimulated groups. However, there were highly significant differences in 2-DG uptake in the contralateral superior olivary complex, contralateral inferior colliculus, and ipsilateral and contralateral lateral lemniscus, with greater uptake in in-depth stimulated preparations. Electrophysiologic and autoradiographic data suggest that a penetrating CN prosthesis is capable of activating the auditory tract at a lower threshold, with a relatively wider dynamic range than a surface prosthesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762792 TI - The cervical sympathetic nerves in surgery of the neck. AB - The otolaryngologist-head and neck surgeon is aware that the cervical sympathetic nerves lie behind the carotid artery and should be avoided during neck surgery. To render this sketchy dictum more tangible, relevant anatomy and physiology of the autonomic supply to the head and neck is reviewed, as are aspects of site-of lesion testing, with respect to Horner's syndrome. Examples of neck operations during which the cervical sympathetic chain--from the base of skull to the root of the neck--may be injured are illustrated. PMID- 1762793 TI - Dematiaceous fungal sinusitis. AB - Six cases of dematiaceous fungal sinusitis are reported, together with a review of 33 other cases collated from a review of the English literature. The sinusitis was more often unilateral vs. bilateral. A characteristic serpiginous hyperdense intrasinus opacification, as well as sinus expansion with bone erosion, was often seen on CT scan. MRI scan showed lucent sinus cavities on T1 and T2 weighting. A comparison of surgical treatment vs. surgery with systemic antifungal therapy revealed decreased recurrence and complication statistics in the combined therapy group. There was a trend toward increased recurrence/persistence and complications associated with invasive histologic findings and only surgical treatment, but not statistically significant. At the present time, we recommend comprehensive surgical treatment followed by systemic antifungal therapy, though clinical judgment and individualization should occur. Future studies are planned to further define the disease entity and its therapy. PMID- 1762794 TI - Mucosal changes induced by experimental pneumococcal otitis media are prevented by penicillin V. AB - Penicillin V (pcV) was administered to 50 rats, either before bacterial challenge (prevention group), or after bacterial challenge but before fulminant purulent acute otitis media (AOM) was established (early treatment group). Five animals from each group were killed on days 4, 8, and 12, and 2 and 6 months after challenge. Middle ear mucosa was sampled at six different sites and studied in the light microscope. Untreated pneumococcal AOM in the rat has been shown to cause persistent structural changes of the middle ear mucosa. Both in the early treatment group and in the prevention group, the structural changes were diminished, as compared with those of untreated infected controls. The persistent structural changes seen after 6 months in untreated controls were not seen in animals that had received pcV in conjunction with the AOM episode. Though the beneficial effect on the mucosal changes during the first 2 weeks was more pronounced when pcV was given prophylactically, its use as early treatment would seem to be almost as effective in preventing the persistence of mucosal changes. PMID- 1762795 TI - Study of phonation in the excised canine larynx. AB - Previous studies have demonstrated that the laryngeal muscles responsible for pitch variation and vocal efficiency are the cricothyroid muscles, affecting longitudinal tension of the vocal folds, and the thyroarytenoid muscles, controlling the lateral stiffness of the vocal folds. Longitudinal tension in the vocal fold is easily simulated in the excised canine larynx. The effect of the thyroarytenoid muscle, however, has not been adequately analyzed. To simulate the effect of the thyroarytenoid muscle, small balloons were placed in the paraglottic space at the level of the vocal folds in 10 excised canine larynges. These balloons (Fogarty catheters) could be inflated in increments to simulate the effect of the thyroarytenoid muscle contraction in altering the lateral stiffness of the vocal fold. During phonation subglottic pressure, vocal fold longitudinal tension and balloon size were systematically varied. The photoglottographic and electroglottographic signals, sound intensity, and airflow rate were measured. Multiple regression analysis showed that sound intensity was directly related to subglottic pressure (p less than 0.001) and inversely related to balloon size (p less than 0.001). Vocal efficiency was directly related to subglottic pressure (p less than 0.001). Frequency of vibration was directly related to balloon size (p less than 0.05), vocal fold tension (p less than 0.001), and subglottic pressure (p less than 0.001). Open quotient was directly related to vocal fold tension (p less than 0.01) and inversely related to balloon size (p less than 0.001). Clinical implications of these results will be discussed. PMID- 1762796 TI - The endoscopic approach to the lateral accessory sphenoid sinus. AB - In summary, an interesting case of an accessory parasphenoid sinus mucocele in a 10-year-old girl is reported. By choosing an endoscopic approach, hearing and balance were preserved, and an external sinus or neurosurgical procedure avoided. The surgery was done on an outpatient basis, with minimal postoperative discomfort and no complications. The mucocele was adequately drained and there has been no recurrence over the following 12 months. PMID- 1762797 TI - Increased intracranial pressure and blindness associated with obstructive sleep apnea. PMID- 1762798 TI - Diagnosis of septic sigmoid sinus thrombosis with magnetic resonance imaging. PMID- 1762799 TI - Acute suppurative thyroiditis with bilateral piriform sinus fistulae. AB - Although there are many possible routes of infection in AST, the clinician must be aware of a possible fistula between the piriform sinus and the perithyroidal space--especially in patients with recurrent episodes of AST. Diagnosis of this congenital tract requires a high index of suspicion and radiographic demonstration by a barium swallow or endoscopic visualization. Effective treatment of AST with intravenous antibiotics and appropriate surgical intervention have greatly reduced the mortality and secondary complications. Complete fistulectomy, however, is required for permanent cure. PMID- 1762800 TI - Home infusion therapy: device, therapy and staffing information. PMID- 1762801 TI - Learning to care for the self: an innovative educational model of the learning process. PMID- 1762802 TI - Nursing interest in research presentations. PMID- 1762803 TI - The B.S.N. requirement for certification: a positive step forward in nursing. PMID- 1762804 TI - Light up your practice with nursing research. PMID- 1762805 TI - Treatment outcome in a multidisciplinary cancer pain clinic. PMID- 1762806 TI - Comparison of intermittent bolus with continuous infusion of epidural morphine in the treatment of severe cancer pain. AB - Twenty-eight patients with severe pain due to cancer, who could no longer obtain acceptable pain relief from optimised doses of oral opioids, were entered into a study which compared pain relief, satisfaction with pain therapy and estimates of neuropsychological functioning during treatment with spinally administered (i.e., epidural and intrathecal) morphine as either repeated bolus doses or as a continuous infusion. These measures of efficacy and side effects were repeated every 2 weeks until either the patient died (82% of patients), withdrew from the study or were no longer able to complete the tests due to deterioration of their condition. The mean (range) duration of treatment was 169 (6-537) days for those patients receiving continuous infusion and 140 (28-378) days for those patients receiving repeated bolus doses. There was no significant difference in visual analogue pain scores, pain relief scores and satisfaction scores between the bolus and infusion groups. Furthermore, low pain scores and high pain relief scores indicated that both treatment modalities provided effective pain control. Similarly, there was no significant difference between the two groups in the various tests used to assess depression or neuropsychological function (i.e., memory, vigilance, attention and processing). There was a significantly greater degree of dose escalation in patients receiving continuous infusion compared to patients receiving repeated bolus doses. For 6 patients in the infusion group the catheter was sited in the intrathecal space, as the dose requirements by the epidural route exceeded the delivery capacity of the pump. For 4 patients in the bolus group the catheter was similarly sited, due to pain on injection and leakage/blockage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762807 TI - The impact of a comprehensive evaluation in the management of cancer pain. AB - To evaluate the importance of a comprehensive evaluation in the management of patients with cancer pain, we surveyed 276 consecutive consultations (226 retrospectively and 50 prospectively) performed by the pain consultant at Memorial Sloan-Kettering Cancer Center. For all consultations, the pain diagnosis, other medical and neurologic diagnoses, investigations and suggested therapeutic interventions were recorded. The pain consultation identified a previously undiagnosed etiology for the pain in 64% of patients in both surveys. Metastatic neoplasm was the most common lesion discovered. In addition, the prospective survey yielded new neurologic diagnoses in 36% of patients and an unsuspected infection in 4%. Eighteen percent of prospectively surveyed patients received radiotherapy, surgery or chemotherapy based on the findings of the pain consultant. These data confirm the importance of a comprehensive neuro-oncologic evaluation in the management of cancer pain. An understanding of oncology, neurology and medicine is critical to assess and treat these patients. PMID- 1762808 TI - Cephalic and extracephalic pressure pain thresholds in chronic tension-type headache. AB - Pressure pain thresholds were assessed with an algometer (Somedic Inc.), over the forehead, temple and suboccipital region as well as over the Achilles tendon. A group of 32 patients suffering from chronic tension-type headache was compared to 20 healthy controls and to 10 migraineurs without aura. Although individual values were widely scattered, pressure pain thresholds were on average significantly lower in chronic tension-type headache, not only at pericranial sites but also over the Achilles tendon. Only 50% of these patients had one or more pericranial thresholds 1.5 S.D. below the mean of controls. After muscular biofeedback therapy, all pain thresholds were on average increased. Along with results obtained previously, the present data support the hypothesis that diffuse disruption of central pain-modulating systems, possibly due to a modified limbic input to the brain-stem, is pivotal in the pathophysiology of chronic tension type headache. PMID- 1762809 TI - Comparative effectiveness of different stimulation modes in relieving pain. Part I. A pilot study. AB - In this pilot study, to assess the optimal stimulation parameters, 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients. Conventional continuous stimulation with a constant frequency of 70 Hz, burst stimulation (90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz, each train consisting of 10 pulses), and frequency-modulated stimulation (continuous pulses changed from 90 Hz to 55 Hz over 90 msec) were randomly delivered to the patients for half an hour in 3 separate sessions. The patients were blind to the modes of stimulation. This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode. PMID- 1762810 TI - Comparative effectiveness of different stimulation modes in relieving pain. Part II. A double-blind controlled long-term clinical trial. AB - Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms - frequency modulation and burst - rather than conventional continuous mode. To assess whether long-term therapeutic effects validate the immediate test results, this trial was performed in 14 patients with 21 pain conditions. Considering the results of the pilot study, the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were randomly delivered to each patient who was blind to the modes of stimulation for 20 min. A second observer assessed the pain scores using visual analogue scales. The stimulation modes employed were: (1) conventional continuous stimulation (continuous pulses with a constant frequency of 70 Hz), (2) burst stimulation (80 msec long trains of pulses, each train consisting of 8 pulses, with an internal frequency of 90 Hz repeated 1.3 times a second), (3) high-rate frequency modulation, HRFM (continuous pulses changed from 90 Hz to 55 Hz over 90 msec, 1.3 times a second), (4) low-rate frequency modulation, LRFM (continuous pulses changed from 60 Hz to 20 Hz over 90 msec, 1.3 times a second). After the test treatment of 4 sessions in the clinic, depending on the pain scores and duration of pain relief recorded, the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home, under our supervision, for 3 months. Fourteen pain conditions out of 21 (66%) responded well to the therapy; the majority preferred was the HRFM and burst-type stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762811 TI - Postoperative pain treated by intravenous L-tryptophan: a double-blind study versus placebo in cholecystectomized patients. AB - The effectiveness of intravenous administration (i.v.) of L-tryptophan, which is the precursor of cerebral serotonin, was verified in the treatment of postoperative pain. The study was carried out on 45 female patients, aged between 34 and 61 years, undergoing cholecystectomy who were randomly divided into three groups. Group 1 (age: 50.33 +/- 8.64 years) received 100 ml of 5% mannitol solution i.v.; group 2 (age: 49.80 +/- 11.11 years) 100 ml of a mannitol solution containing 7.5 mg/kg L-tryptophan; and group 3 (age: 53.46 +/- 9.60 years) 100 ml of a mannitol solution containing 15 mg/kg L-tryptophan. Vital capacity (preoperative VC) was measured before surgery. Anesthesia used was isoflurane. Narcotics or neuroleptics were not used. Pain was assessed before treatment (T-0 min), at the end of administration (T-30) and at T-60, 120, 180, 240, 300 and 360 min by the following variables: respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), Scott-Huskisson test (VAS), pain vital capacity (PVC), analgesic vital capacity (AVC), and respiratory restoration factor (RRF) calculated from Bromage's formula (RRF = (AVC - PVC/preoperative VC - PVC) X 100). As regards variables RR, HR, MAP and VAS, differences between the values from T-30 to T-360 and the value at T-0 were calculated. Means and S.E.M. were calculated on the obtained values and on RRF values for each group. The significance of the differences between groups was calculated using Student's t test and Bonferroni's test. Results show a significant decrease of pain in groups 2 and 3 treated with L-tryptophan, in comparison with group 1 (controls). No significant difference was observed between the treated groups, although more lasting pain relief was observed in group 3 in comparison with group 2. Intravenous L-tryptophan showed its effectiveness in the treatment of postoperative pain even when used alone. Its use may be considered for patients with renal failure, in order to strengthen pharmacological analgesia or to prevent postoperative pain by its intraoperative administration. PMID- 1762812 TI - Cerebral event-related responses induced by CO2 laser stimulation in subjects suffering from cervico-brachial syndrome. AB - The present study was undertaken to examine possible changes in subjective appraisal and central nervous system processing, indexed by pain-related cerebral evoked potentials (N290, P400), of incoming noxious information in 20 pain-free control volunteers and 18 subjects suffering from right-side cervico-brachial pain (CBS). Detection threshold and cerebral evoked potentials were recorded in response to noxious CO2 laser stimulation of the right and left hands. The results indicate that when compared to controls, CBS subjects exhibit an elevation in detection threshold intensity and a reduction in the amplitude of the P400 peak following laser stimulation of the pain affected side. There were also differences in the choice of qualitative descriptor for laser stimuli although not in the subjective rating of stimulus intensity. These changes were not apparent for responses on the unaffected limb. The severity of clinical pain was found to be related to the magnitude of reduction in P400 amplitude only on the pain affected side. Conversely, feelings of anxiety were associated with higher amplitude responses on both the right and left sides, suggesting a more generalized relationship between these factors. We interpret these findings to indicate an alteration in central nervous system processing and subjective appraisal of acute experimental pain in subjects with chronic CBS. Moreover, these alterations appear to be restricted to pain affected pathways and are more related to the severity of clinical pain than to general mood state. PMID- 1762813 TI - Psychosocial factors in chronic spinal cord injury pain. AB - Chronic pain is a problem among patients with spinal cord injuries, but the psychosocial factors associated with spinal cord injury (SCI) pain are not well understood. To understand SCI pain further, 54 patients (19 with quadriplegia and 35 with paraplegia) completed the Beck Depression Inventory, State-Trait Anxiety Inventory, Profile of Mood States, Acceptance of Disability Scale and SCI Interference Scale. Forty-two patients stated they had SCI pain and completed the Multidimensional Pain Inventory and the Pain Experience Scale. Results revealed that anger and negative cognitions were associated with greater pain severity. Patients who reported pain in response to a general prompt experienced more severe pain than patients who reported pain only when directly questioned about the presence of pain, but these different reporting groups did not differ on emotional variables. Those who were less accepting of their disability reported greater pain severity. Additionally, patients who perceived a significant other expressing punishing responses (e.g., expressing anger at the patients or ignoring the patients) to their pain behaviors reported more severe pain. Level of lesion, completeness of injury, surgical fusion and/or instrumentation and veteran status were not associated with pain severity. Finally, pain was associated with emotional distress over and above the distress associated with the SCI itself. Overall, psychosocial factors, not physiological factors, were most closely associated with the experience of pain. Multidimensional aspects of pain are used to explain these findings and suggest that treatment should be directed at the emotional and cognitive sequelae of chronic SCI pain. PMID- 1762814 TI - Consensus and contention in the treatment of chronic nerve-damage pain. AB - A postal questionnaire survey was carried out to investigate beliefs in the efficacy of specific treatments held by consultants involved in the treatment of chronic nerve-damage pain. One hundred eighty-eight consultants experienced in the treatment of chronic pain were identified by local Pain Clinic consultants in 5 centres. The specialties represented were neurology, neurosurgery, orthopaedic surgery, oncology/radiotherapy, plastic surgery and anaesthesia. Replies were received from 181 consultants (96%). Over one fifth of the consultants expressed no opinion about half of the treatments assessed. Widely divergent views were held by those who did give an opinion. Many clinicians assessed some treatments as 'poor' while other clinicians assessed the same treatments as 'excellent' (neurolytic nerve block, somatic nerve block, cordotomy and opioids). For some treatments divergence of opinion can be explained in part by differences between specialties. For other treatments marked diversity was seen within as well as between specialties. There is a clear need for education in the use of particular treatments, even amongst those clinicians who regularly see this type of patient. PMID- 1762815 TI - The validity of the General Health Questionnaire for first-stage screening for mental illness in pain clinic patients. AB - The validity of the 28-item version of the General Health Questionnaire (GHQ-28) was determined by comparison with the Clinical Interview Schedule (CIS) in 56 pain clinic patients. Despite some limitations, the GHQ can be used effectively and cheaply as the first stage of an assessment to identify potential "cases" of mental disorder which must then be verified using a second-stage clinical interview such as the CIS. This process can result in a considerable reduction in the proportion of patients requiring a psychiatric interview and, therefore, in reduced service costs. Factors associated with lower validity coefficients include female sex, age above 60 years and pain with a duration of less than 2 years. PMID- 1762816 TI - The expression of a deafferentation syndrome in the Sprague-Dawley rat: effects of frontoparietal cortical lesions. AB - Forelimb sensorimotor (SMI) cortical lesions in the rat have been found to suppress a deafferentation syndrome which follows C5-T2 ganglionectomy/avulsion whether the cortical lesions were made prior to, or several days after, the dorsal root lesions. None of the 6 rats with only frontoparietal lesions developed a deafferentation syndrome. These results may be influenced by the presence of a sensorimotor amalgam in the parietal cortex of the rat. PMID- 1762817 TI - Differentiating analgesic and non-analgesic drug activities on rat hot plate: effect of behavioral endpoint. AB - The contribution of behavioral endpoint to results obtained in the 55 degrees C rat hot plate procedure was assessed. Specifically, the use of a hind paw lick only endpoint was compared to that of a hind paw lick-or-jump endpoint. Effects of prototypical analgesic and non-analgesic compounds on response latency increases were determined under each condition. Whereas the effects of morphine, oxycodone and codeine were similar under each condition, effects of a number of non-analgesic agents differed markedly depending upon the endpoint used. Clozapine, chlorpromazine, thioridazine, atropine, scopolamine, benactyzine, yohimbine, idazoxan and cyproheptadine produced dose-dependent increases in response latency under the hind paw lick-only condition but did not increase latencies when the hind paw lick-or-jump endpoint was used. Haloperidol, sulpiride, benztropine, methyl atropine, phentolamine, prazosin, methiothepin, methysergide, diphenhydramine, pargyline and diazepam failed to increase response latencies under the hind paw lick-only condition. Moreover, whereas diazepam, chlorpromazine, pentobarbital, dantrolene and ethanol produced dose-dependent increases in the height required for successful aerial righting, increases in hind paw lick-or-jump latencies occurred only following near-anesthetic doses of pentobarbital and ethanol. These data indicate that the hind paw lick endpoint is susceptible to perturbation by extraneous pharmacologic activities. Drugs exerting muscarinic cholinergic and alpha 2-adrenergic antagonist effects are particularly able to disrupt this behavior. Disruption is not associated specifically with any other pharmacologic action, although other activities may interfere with the response. In contrast, the hind paw lick-or-jump endpoint fails to detect skeletal muscle relaxant activity and only detects gross motor impairment when near-anesthetic doses of drugs are used. The present data suggest that detection of non-analgesic drug activities by rat hot plate can be minimized by use of a hind paw lick-or-jump endpoint. PMID- 1762818 TI - Spinal co-administration of cholecystokinin antagonists with morphine prevents the development of opioid tolerance. AB - The effects of intrathecal (i.t.) co-administration of the cholecystokinin (CCK) antagonists lorglumide or proglumide with a "low" (1 microgram) and "high" (10 micrograms) dose of i.t. morphine on the development of opioid tolerance were determined using the rat tail-flick assay. Although co-injection of 7 ng lorglumide or 20 ng proglumide (doses which have been demonstrated to acutely enhance 1 microgram morphine, i.t.) were without effect, co-administration of 70 ng lorglumide or 64 ng proglumide with 1 microgram morphine for 6 days inhibited development of tolerance to this dose of opioid. Higher doses of CCK antagonists (1400 ng lorglumide and 1280 ng proglumide) were required to prevent the tolerance induced by 10 micrograms morphine. These findings provide further evidence that CCK mediates, at least partially, tolerance which develops to the analgesic effect of opioids and indicate the involvement of CCK pathways in the spinal cord. The results are also consistent with a mechanism in which the level of activation of compensatory, anti-opioid CCK circuitry is increased in proportion to the functional level of opioid pathways. PMID- 1762819 TI - The antinociception evoked by anterior pretectal nucleus stimulation is partially dependent upon ventrolateral medullary neurones. AB - Electrical stimulation (35 microA rms/15 s) of the anterior pretectal nucleus (APtN) inhibits the spinal reflex of the tail-flick (TF) to noxious heat in unanaesthetised rats. APtN stimulation also reduces the nociceptive response of spinal dorsal horn neurones in halothane-anaesthetised rats. This study determined if the antinociceptive effects of APtN stimulation depended on neurones in the ventral medulla. Bilateral electrolytic lesions of the ventrolateral medulla, but not the nucleus raphe magnus, reduced by 70% the antinociceptive effect of APtN stimulation in the TF test. In rats anaesthetised with halothane, electrical stimulation of the APtN (single square wave 0.1 msec pulses, 2-20 microA, 1 Hz) excited cells in the ventrolateral medulla. These data suggest a connection between both areas. This connection is further confirmed by neuroanatomical tract tracing studies in which the retrograde dye Fast Blue was injected into the ventrolateral medulla. Fluorescent cell bodies were found in the APtN. We therefore conclude that the ventrolateral medulla is part of a descending antinociceptive pathway from the APtN. PMID- 1762820 TI - Comment on 'Ischaemic spinal cord lesion following percutaneous radiofrequency spinal rhizotomy' by H.M. Koning, H.G. Koster and R.P.E. Niemeijer in Pain, 45 (1991) 161-166. PMID- 1762821 TI - Ignorance of photobiology: a major pitfall in using lasers in medicine. PMID- 1762822 TI - Comments on 'The analgesic effects of caffeine in headache,' by D. Avery, D. Dunner, N. Ward and C. Whitney in Pain, 44 (1991) 151-155. PMID- 1762823 TI - Nail gun injury. AB - Traumatic penetrating wounds caused by compressed air or pneumatic tools initiate local tissue changes that are similar to gunshot wounds. Wounding caused by a pneumatic nail gun can range from mild tissue damage to severe life-threatening injury. This article presents a case review with appropriate nursing diagnoses. PMID- 1762824 TI - Limitsetting: dealing with difficult patients. AB - "Limitsetting" is an overall term for interventions that decrease problematic behavior. Orthopaedic units seem to have more than their share of patients with problematic behavior. Reasons for this include the pain, immobility, and body image changes as well as the fact that preinjury personality factors may include impulsive and angry dynamics. The limits set must match the behavior manifested. Dangerous behavior, the highest priority, demands an immediate, decisive strategy. Direct statements should be concrete and specific with positive, absolute directives of what must be done. Two case studies are included. PMID- 1762825 TI - The orthopaedic critical path. AB - Health care providers, purchasers, and insurers are struggling to manage the cost of health care while maintaining the quality of care. Alliant Health System has incorporated Total Quality Management (TQM) and the Critical Path Process throughout the corporation as a managed care strategy to deliver cost-effective quality care. Using the Critical Path Process has demonstrated a reduction in Length of Stay (LOS) and cost while maintaining quality. The success of this process depends upon an interdisciplinary and collaborative approach among health care providers in identifying practice patterns to assure appropriate and timely delivery of patient care. PMID- 1762826 TI - Children and pain: easing the hurt. AB - Relief of pain in children is a challenge to the pediatric health care provider. A clear understanding of the various developmental and cognitive levels will help the nurse better assess and manage children in pain. Age-appropriate assessment tools are currently available. A combination of a wide variety of treatment modalities, both pharmacologic and nonpharmacologic, can be used to effectively manage pain in children. PMID- 1762827 TI - Patient perceptions of pain and disability after joint arthroplasty. AB - Patients having elective total hip or knee arthroplasty are routinely assessed for flexibility, muscle strength, and gait both preoperatively and postoperatively, but there appears to be limited information available on patients' self-reported pain levels. This study used two self-report measures of health status and a pain scale to measure patients' perceptions of disability and pain immediately prior to surgery and at 6 weeks and 6 months after total hip or knee arthroplasty. PMID- 1762828 TI - Guidelines for master's degree in orthopaedic nursing. PMID- 1762829 TI - Femoral neck stress fracture. PMID- 1762830 TI - Specialty nurse organizations develop position statements. PMID- 1762831 TI - Initial assessment and management of a patient with a gunshot wound to the femur. AB - As the number of violent crimes rise, the likelihood increases that the nurse will be faced with patients presenting with gunshot injuries. These wounds pose a significant challenge to the nurse working in the acute care setting. Unlike other penetrating trauma, gunshot wounds produce a myriad of associated injuries related to the mechanism of injury. Nurses must be aware of the specific trauma associated with these wounds to assess and manage the victim in an organized and systematic fashion. PMID- 1762832 TI - [Cell polarity and protein transport in digestive epithelial cells]. PMID- 1762833 TI - Purified recombinant CD4 inhibits HIV-1 infection of peripheral blood macrophages. AB - Purified recombinant soluble CD4 (rCD 4) is a new antiviral agent which has been shown to block HIV infection of lymphocytic and monocytic cell lines as well as peripheral blood mononuclear cells. The authors investigated here the ability of rCD4 to inhibit HIV-1 infection of peripheral blood macrophages. In this system, purified preparations of rCD4 provided, at concentrations above 10 micrograms/ml, a complete protection against a challenge with the monocytotropic strain HIV-1 Ba L. Also, anti-CD 4 monoclonal antibodies directed at the V1 domain of the CD 4 molecule blocked infection of macrophages by HIV. Recombinant CD 4 is therefore a potent antiviral agent able to prevent HIV-1 infection of peripheral blood macrophages, and the CD 4 molecule is likely to be the main HIV receptor on these cells. PMID- 1762834 TI - [Cholecystitis and biliary infection]. AB - Cytobacteriologic study of 150 gallbladder fluid samples obtained before cholecystectomy found no correlations between clinical manifestations, gross and histologic features of the gallbladder, and underlying biliary infection. The potential parts played in these discrepancies by bile, time to surgery, and use of antimicrobial agents are discussed. PMID- 1762835 TI - [Study of the bactericidal effect of cefpodoxime using an in vitro pharmacokinetic model]. AB - Cefpodoxime is a new oral prodrug antibiotic. Following absorption from the proximal intestine, non-specific esterases hydrolyze this cleavable ester, releasing cefpodoxime, a new broad-spectrum third-generation cephalosporin with sustained plasma levels in humans. Cefpodoxime killing kinetics were studied using an in vitro model which simulates the pharmacokinetic profile obtained in healthy volunteers given a single oral dose of cefpodoxime proxetil providing 100, 200 or 400 mg active cefpodoxime. Cefpodoxime exhibited strong antibacterial activity against tested strains of Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus. These results suggest that use of two daily doses of 100 or 200 mg each are appropriate for the treatment of E. coli and S. pneumoniae infections in view of the pharmacokinetic properties of cefpodoxime. Less intensive therapy is probably adequate in uncomplicated community-acquired urinary tract infections. The bactericidal effect of cefpodoxime against S. aureus is prolonged due to a postantibiotic effect. PMID- 1762836 TI - [Evaluation of the prevalence of side effects of phenobarbital in patients in the Champagne-Ardenne region]. AB - Side effects were compared in 454 patients under phenobarbital and in 133 patients under other antiepileptic agents. Prevalence of adverse effects was 12% and 4% in these two groups, respectively. The fairly low prevalence of untoward reactions to phenobarbital in this study as compared with previously published reports is due to the methodology used. Despite unquestionable drawbacks, especially in patients above 50 years of age at first use, phenobarbital is a valuable therapeutic alternative in some cases. PMID- 1762837 TI - [Identification of a type 1 macrocreatine kinase]. AB - A macrocreatine-kinase type 1 was identified by CK isoenzyme electrophoresis of a serum sample from a patient. Constituents of this enzyme complex were studied. The isoenzyme present in the macrocreatine-kinase was identified using immunoprecipitation with antibodies against the M subunit. Affinity chromatography then determined the type of the immunoglobulin bound to the CK isoenzyme. A protocol for studying macrocreatine-kinase type 1 compounds is proposed. PMID- 1762838 TI - [The blood-brain barrier: implications for chemotherapy in brain tumors]. AB - The blood-brain barrier (BBB) is located between the blood and the extracellular space of the brain. This barrier is formed by the brain capillaries whose endothelial cells have tight intercellular junctions. Transcellular passage of drugs from the bloodstream to the brain occurs selectively, in a manner dependent on the ability of the molecules to penetrale through cell membranes. The blood brain barrier is one of the main factors of chemotherapy failure in central nervous system tumors. Penetration of a molecule from the bloodstream to the brain is dependent on the compound's liposolubility, expressed by the octanol water separation coefficient. Following intravenous administration, most drugs fail to achieve adequate levels in the central nervous system for a sufficiently long period of time. A variety of techniques have been used in an attempt to increase CNS penetration of drugs normally shut out by the blood-brain barrier: high-dose chemotherapy, intrathecal injections, intraarterial injections, induction of hyperosmolarity to make the blood-brain barrier permeable. The best results are obtained using liposoluble drugs with optimal octanol-water separation coefficients, such as fotemustine. This compound given as single drug therapy in brain metastases from malignant melanomas has yielded response rates of up to 28.2%. PMID- 1762839 TI - [Natural tyrosine-kinase inhibitors]. AB - Changes in the degree of phosphorylation of protein tyrosine residues play a major role in the regulation of cell growth and differentiation. The biological mechanisms which control the activity of enzyme systems involved in these change (i.e. protein tyrosine-kinase [PTKs] and protein tyrosine-phosphatases) remain poorly understood. Similar to other regulation mechanisms, involving phosphorylation-dephosphorylation reactions, these enzyme systems can be regulated by naturally occurring effectors (with inhibitory or activating effects). This paper briefly reviews current knowledge on the few identified natural PTK inhibitors. The phosphoprotein PP 63 produced by rat hepatocytes inhibits insulin-receptors PTK in hepatoma cell cultures and abolishes insulin's mitogenic effect. PP 63 has a slight structural resemblance with Mullerian Inhibiting Substance, a molecule reported to inhibit epidermal growth factor (EGF) receptor PTK and to exhibit anti-mitogenic effects. Two other proteins, protein S-100 isolated from cattle brain and a thermostable factor found in human lymphoid tissues also have anti-PTK effects. Although in the current state of our knowledge, the physiologic role of these inhibitors is unclear, they may have potential value as anti-oncogenic agents as a result of their ability to decrease phosphorylation of protein tyrosine residues. PMID- 1762840 TI - [Chromium: physiologic role and implications in human pathology]. AB - Reported values for total body stores of chromium vary between 0.4 mg and 6 mg. Chromium stores may be higher in neonates than in adults, relative to body size, whereas tissular chromium may be depleted in the elderly. The recommended daily allowance for chromium is 50 to 200 micrograms/day but actual needs are poorly known. Digestive absorption is better for organic chromium, which is part of the "glucose tolerance factor" (GTF), than for inorganic chromium. Furthermore, chromium (VI) is better absorbed than chromium (III). In the body, chromium (VI) is rapidly reduced to chromium (III) by a number of metabolic pathways. Absorbed chromium binds to proteins, mainly to transferrin which exhibits a high affinity for chromium (III). Most absorbed chromium is eliminated through the kidneys. Renal excretion occurs according to a two or more-compartment model. Current methods used to assay chromium, i.e., atomic absorption spectrometry using a graphite furnace or neutron activation, are sufficiently sensitive and specific to evaluate chromium levels in blood, urine or hair. However, none of these levels accurately reflects chromium body stores. Chromium is part of the GTF molecule. This factor has no effect per se but may facilitate binding of insulin to insulin receptors and amplify the effects of insulin on carbohydrate and lipid metabolism. Chromium deficiency may play a role in a development of some forms of adult diabetes mellitus and of arteriosclerosis. Partial chromium deficiencies seem to be common, especially in individuals with high intakes of refined foods. Acute chromium poisoning is usually due to an excess of chromium (VI) and is sometimes seen in the chromium industry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1762841 TI - [Malherbe's necrotizing epithelioma in a 6-year-old child]. PMID- 1762842 TI - [A case of cutaneous-visceral mastocytosis in a 13-year-old boy]. PMID- 1762843 TI - [A dysontogenetic cyst of the stomach in a child]. PMID- 1762844 TI - [Eosinophilic granulomas of the bones of the skull in children]. PMID- 1762845 TI - [Immunity in 6-year-old children born to women with a history of late pregnancy toxicosis]. PMID- 1762846 TI - [Immunity in patients with the Macleod syndrome]. PMID- 1762847 TI - [The dynamic lysozyme activity of the bronchial secretion in children in the acute period of pneumonia]. PMID- 1762848 TI - [The clinico-genetic characteristics of children with local forms of primary tuberculosis]. PMID- 1762849 TI - [Hemostasis and the blood lipid spectrum in children with a hereditary disposition for arterial hypertension and the autonomic vascular dystonia syndrome]. AB - Overall 75 children aged 7-13 years with hereditary load as regards arterial hypertension were examined. Hemocoagulation, the content of total cholesterol and triglycerides in blood serum, and that of cholesterol in high density lipoproteins were estimated in children with and without vegetovascular dystonia. The changes in blood lipids of the atherogenic nature, activation of the processes of coagulation were coupled with vegetovascular dystonia and showed up maximally when combined with initial sympathicotonia, hypersympathicotonic reactivity, and with the hyperdiastolic variety of the clino-orthostatic test. The children with hereditary load as regards arterial hypertension and with vegetovascular dystonia should be attributed to the high risk group in order to carry out follow-up studies and a complex of treatment and health measures. PMID- 1762850 TI - [The characteristics of the personality interrelations of adolescents with different forms of secondary arterial hypertension]. AB - Interpersonality relations and conflict situations were studied in patients who need psychological correction. In patients with symptomatic arterial hypertension, the degree of dissatisfaction was estimated according to the following three scales: educational ("Conflict Situations at School" including conflicts with friends); family and household ("Conflict Situations in the Family"); and "Internal Disputed Matters". The patients with symptomatic arterial hypertension of the nephrogenous and endocrine genesis may turn out more conflicting since they are trying to discover the cause of their life failures in their social surrounding rather than in their personal inability to cope with them because of the disease. PMID- 1762851 TI - [Clinico-laboratory criteria in the diagnosis of ARVI and respiratory allergoses in children]. AB - Overall 219 ailing children aged 3 to 14 years were examined, using the disease history, clinical, morphological, immunological and cytochemical data. There were 115 patients with allergoses and 104 patients suffering from acute respiratory viral infections (ARVI). A retrospective analysis has demonstrated that in 52.6% of the children, respiratory allergosis diagnosis was late (3-5 years since its onset). It has been established that hereditary allergic load, food and drug allergy, local eosinophilia of the nasal mucosa as well as a decrease of E-RFC, a rise of EAC-RFC levels, a lower T/B index, dysgammaglobulinemia marked by significant stable alterations in patients with respiratory allergoses and transitory, obscure changes associated with ARVI can serve differential diagnostic criteria. PMID- 1762852 TI - [Endocrine status changes in children with bronchial asthma]. AB - A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of glucocorticoid receptors in lymphocytes as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years. The authors revealed alterations in the functional activity of the indicated endocrine glands depending on the intensity of bronchial patency disorders and the nature of the therapeutic measures carried out. PMID- 1762853 TI - [The vaccination of children with allergic diseases with reduced doses of adsorbed DT-m anatoxin]. AB - During a remission and drug therapy, 71 children suffering from allergic diseases were vaccinated with DT-M toxoid containing different dose of diphtheria (1, 2.5, 5 LF) and tetanus (1, 2.5, 5 EC) antigens. It has been shown that all the children responded to tetanus antigen by adequate serological tests, whereas as regards diphtheria toxoid, the patients immunized with the least dose of DT-M preparation (1 LF + + 1 EC antigens) produced specific antibodies later and at a lower level. During the postvaccinal period, they also manifested an increase of the content of IgE and exacerbation of the underlying disease in 17.8% of cases. The use of DT-M toxoid with 2.5 LF + EC antigens was shown to hold promise in vaccination of children suffering from allergic diseases. PMID- 1762854 TI - [A pharmacokinetic basis for schedules for administering amikacin to newborn infants]. AB - The use of correlations between the pharmacokinetic parameters and the patient's factors is one of the most promising trends in the elaboration of the efficient regimens of dosage. To establish the analogous correlations in terms of specifying the causes of the widely known individual variability of serum aminoglycoside concentrations in 139 neonates given amikacin for suggested or documented infections, a study was made of the drug pharmacokinetics. PMID- 1762855 TI - [The serum and tissue concentrations of antibiotics used in pediatric pulmonology]. AB - Measurements were made of the concentrations of different antibiotics in children with acute and chronic pneumonia. The data obtained do not only confirm the dependence of the peak concentration of the drug in blood serum and tissue fluid on the antibiotic single dose but also point to a direct relationship between the single dose and duration of a high drug concentration in the body. It has been established that parenteral drugs penetrate well the pleural cavity, making it inadvisable to administer antibiotics intrapleurally in the treatment of acute pneumonias complicated by exudative pleurisy. In chronic pneumonia, the maximal content of antibiotic in pulmonary tissue reaches 30% of its serum concentration 2.5-3 hours after a single intramuscular drug injection. Study of the pharmacokinetics of antibiotics administered per os in the treatment of acute pneumonia attests to their rapid absorption from the gastrointestinal tract; as a rule, the peak concentrations were recorded 1 hour after the drug intake and exceeded many times the minimum inhibitory concentration for pneumococci isolated from the patients placed under observation. PMID- 1762856 TI - [The functional diagnosis of bronchial hyperreactivity and bronchial lability in children with bronchial asthma]. AB - During a remission, bronchial asthma children were examined for bronchial hyperreactivity and bronchial lability by means of graded physical exercise tests, and pharmacological tests with bronchoconstrictors and bronchodilators. It has been established that normal lung function seen during aa remission does not mean the lack of bronchial hyperreactivity whereas incomplete recovery of bronchial patency during bronchial asthma remission is always attended by bronchial hyperreactivity in almost all the cases. In carrying out functional tests for bronchial hyperreactivity and bronchial lability, the recording of the velocity parameters of forced expiration making it possible to define patency of not only the central but also of the peripheral bronchi appeared very informative. PMID- 1762857 TI - [The functional diagnosis of irreversible changes in the bronchi in chronic pneumonia in children]. AB - The recording of biopotentials of smooth muscle fibers of the bronchial wall in chronic pneumonia patients enables one to evaluate the degree of their impairment and to differentiate between reversible and irreversible lesions. Assay of the electromyobronchograms makes bronchological information more precise, allowing prediction of the further course of the inflammatory focus in the lungs. Functional diagnosis of the affected parts of the respiratory system is helpful in choosing an optimal treatment schedule, promoting improvement of the long-term results of both conservative and surgical treatment of patients with chronic respiratory pathology. PMID- 1762858 TI - [The status and outlook of immunoprophylaxis in the USSR]. PMID- 1762859 TI - [The types of attitude to disease in functional disorders of the reproductive system at puberty]. PMID- 1762860 TI - [Lipid peroxidation and antioxidant system functions in staphylococcal sepsis in nursing infants and the principles of pathogenetic therapy]. PMID- 1762861 TI - [Neurological disorders and the problem of hip joint dysplasia in nursing infants]. PMID- 1762862 TI - [The characteristics of the clinical manifestations and the prognosis of the outcome in suppurative meningitis in infants in the first 2 years of life]. PMID- 1762863 TI - [Chronic granulomatous disease: the spectrum of the clinico-laboratory disorders and the therapeutic procedure]. PMID- 1762864 TI - [The phytotherapy of children with thrombocytopenic purpura]. PMID- 1762865 TI - [The treatment of a high fever in young children at the prehospital stage]. PMID- 1762866 TI - [The treatment of children in a critical state with a combined course of bacterial intestinal and acute respiratory viral infections]. PMID- 1762867 TI - [The characteristics of lipid metabolism in children with primary arterial hypertension]. AB - Overall 183 children with arterial hypertension (AH) were examined. Of these, 122 suffered from primary arterial hypertension (PAH). The lipid spectrum was defined in blood plasma of 95 children with PAH and in 30 normals. The same investigation was carried out in 109 parents of the children suffering from PAH. The lipid spectrum was established to be heterogeneous. 77.9% of the patients had dyslipidemia. A significant relationship was established between the stage of PAH and the nature of lipidemia as was a close interrelation between alterations in the lipid spectrum of blood plasma and hereditary load as regards essential hypertension. PMID- 1762868 TI - [The evolution and current characteristics of the clinical picture and treatment of brucellosis in children]. PMID- 1762869 TI - [Medical ethics and deontology from the aspect of gynecology in children and adolescents]. PMID- 1762870 TI - [The clinico-instrumental characteristics of gastroesophageal and duodenogastric refluxes in children]. PMID- 1762871 TI - Virtually real. PMID- 1762872 TI - Induced motion: isolation and dissociation of egocentric and vection-entrained components. AB - Induced motion (IM) is illusory motion of a stationary test target opposite to the direction of the real motion of the inducing stimulus. We define egocentric IM as an apparent motion of the test target relative to the observer, and vection entrained IM as an apparent motion of a stationary object along with an apparent motion of the self (vection) induced by the same stimulus. These two forms of IM are often confounded, and tests for distinguishing between them have not been devised. We have devised such tests. Our test for egocentric IM relies on evidence that this form of IM is due mainly to a misregistration of eye movements when optokinetic nystagmus (OKN) is inhibited, and on evidence that OKN is evoked only by stimuli in the plane of convergence. Our test for vection-entrained IM relies on evidence that vection is evoked only by the more distant of two superimposed inducing stimuli. Thus we found egocentric IM to be induced without vection or vection-entrained IM when subjects converged on a foreground moving display with a stationary display in the background, and vection-entrained IM to be induced without egocentric IM when subjects converged on a stationary foreground display with a moving display in the background. The two types of IM were evoked in opposite directions at the same time when subjects converged on a foreground moving display while a background display moved in the opposite direction. The two forms of IM showed no signs of interaction, and we conclude that they rely on independent motion mechanisms that operate within distinct frames of reference. A control experiment suggested that the depth adjacency effect in IM is determined by the depth adjacency of the inducing stimulus to convergence, not just to the test target. PMID- 1762873 TI - Gender differences in apparent motion perception. AB - Distance disparity is a strong cue to element correspondence in apparent motion. Using a 2-AFC paradigm we have previously shown that shape similarity also plays a role. We now demonstrate a small gender difference in these effects: women are more sensitive to distance disparity, whereas men are more sensitive to differences in shape. Furthermore, in the competing presence of a shape cue, women's sensitivity to distance decreases while men's sensitivity is unaffected. These observations may be related to putative gender differences in the 'form' and 'motion-spatial relations' cortical pathways. PMID- 1762874 TI - Shape discrimination for motion-defined and contrast-defined form: squareness in special. AB - Shape discrimination was measured for: (i) two-dimensional rectangular targets that were perfectly camouflaged within a stationary pattern of random dots and rendered visible by relative motion of the dots, and (ii) similar dotted rectangles that were rendered visible by luminance contrast. Shape discrimination was disconfounded from size discrimination by requiring subjects to discriminate the aspect ratios of rectangles whose areas were altered independently of aspect ratio. When dot speed and contrast were both high, the aspect-ratio discrimination threshold was as acute for motion-defined (MD) rectangles as for contrast-defined (CD) rectangles and, at 2-3%, corresponded to a change of side length of about 24 s arc compared to a mean dot separation of 360 s arc. Discrimination of MD rectangles collapsed at low dot speeds and could not be measured at speeds less than about 0.03-0.08 deg s-1, but discrimination of CD rectangles was almost unaffected by dot speed. The aspect-ratio discrimination threshold was lowest for a square and progressively increased as the rectangle became more asymmetric. It is suggested that the visual system contains a mechanism that compares the separations of pairs of contours along different azimuths, and that, during visual development, this shape-discrimination processing of MD and CD targets is driven by the same environmental and behavioural pressures towards a common end point. The human equivalent of a pathway that includes the cortical area MT is thought to be important for shape discrimination of MD forms. PMID- 1762875 TI - On the salience of the inducer's displacement in induced rotary movement. AB - It has been reported that an annulus patterned with two equally-spaced radial lines elicits slower induced rotary movement than an annulus patterned with sixteen equally-spaced radial lines. This has been attributed to the quantity of inducing stimulation. However, the number of pattern elements also affects the time course of induced rotary movement: it can be intermittent with two-radii inducers, but persistent with sixteen-radii inducers. Displacement of a two-radii inducer may be more salient to the subject than displacement of a sixteen-radii inducer: from time to time the displacement of the former may come to dominate perception, suppressing induced movement. Hypotheses invoking quantity of stimulation and salience of inducer displacement were tested by way of inducers with different numbers and spacings of pattern elements. Subjects timed induced rotary movement (experiment 1) and a subsequent aftereffect (experiment 2). The results were consistent with both the quantity of stimulation (experiments 1 and 2) and the salience of inducer displacement (experiment 2) having an effect. This suggests that at least two mechanisms may be involved in induced rotary movement. PMID- 1762876 TI - Serial search for targets defined by divergence or deformation of optic flow. AB - The optic flow field can be described in terms of the local differential measures, divergence, deformation, and rotation, which are informative about observer motion and the 3-D structure of the environment. Does an explicit representation of these measures exist in human visual processing in the form of a feature map? Triesman's criteria were used to investigate this; ie is there 'pop-out' for a target defined as different in local divergence or deformation from surrounding elements, or is a serial search necessary? The stimulus arrays contained 3, 5, or 9 square or rectangular elements, which each underwent repeated cycles of expansion, contraction, or deformation. The time required to detect a target undergoing the opposite transformation increased steeply with the number of elements, implying very slow serial search. (The mean time was 210 ms per element for divergence targets and 542 ms per element for deformation). The process was clearly still serial when the density and number of elements was increased up to 48 in an array 2.16 deg x 2.16 deg. In contrast, a single line element undergoing the opposite direction of translation motion to the rest of the display did show pop-out. It is concluded that no parallel processes seem to exist which are sensitive to the spatial uniformity of divergence and of deformation of optic flow. These differential properties may be derived as conjunctions of signals from a primary process which extracts local velocity. This result contrasts with our findings for targets defined by stereo disparity gradient, which show parallel processing in analogous experiments. PMID- 1762877 TI - Pre-attentive detection of a target defined by stereoscopic slant. AB - Does the visual system represent stereoscopic depth purely as a map of local disparities, or does it explicitly represent local relationships of disparity, such as disparity gradients? Experiments are reported in which visual search for a target containing the same disparity range as other elements in the display, but differing in the relationship of the disparities (stereo slant), was used to determine whether the target showed 'pop-out' like a unitary feature, or the serial search characteristic of feature conjunctions. Each stereo pair of elements was selected randomly from a range of outline parallelograms leaning to the right or to the left, so that the target could not be identified using any monocular shape cue. Response times for detection of the target (present on 50% of the trials) were independent of the number of elements in the display. This result was confirmed by varying element size and spacing, and by using oblique crosses rather than parallelograms as stimuli. It is concluded that stereoscopically defined slant, or disparity gradient, can be processed and compared in parallel across the display, and acts in this respect as an explicit unitary visual property. This contrasts with findings in analogous experiments on movement, which show that targets defined by divergence or deformation of optic flow can only be identified by serial search. PMID- 1762878 TI - Training effects on dynamic visual acuity with free-head viewing. AB - Training effects on dynamic visual acuity (DVA) were determined over a range of target durations and target velocities under the viewing condition of free-head movement. Dynamic acuity levels were lower than static acuity levels, and training was found to be very effective in improving performance, particularly under the most difficult conditions in which performance was poorest. Improvement was also most evident among those observers who initially exhibited the poorest DVA scores. Preliminary comparisons between DVA scores of a nonselect sample of college students and those of a small group of college athletes indicated that the athletes were not very different from the nonselect group and would also benefit from training on the task. PMID- 1762879 TI - Comparison of contrast sensitivity functions across three orientations: implications for theory and testing. AB - The contrast sensitivity functions of a large group of observers (N = 71) were determined for three orientations of test gratings: vertical, oblique, and horizontal. Comparison of group means indicated that, consistent with previous findings for the 'oblique effect', sensitivity was poorer for the oblique orientation-but only for the mid-high spatial frequencies. Correlation analyses indicated that contrast sensitivity for a particular spatial frequency at a given orientation was highly correlated with contrast sensitivity for that same frequency at the other two orientations. Factor analysis of the intercorrelations revealed two strong factors, a low frequency factor, and a mid-high frequency factor. Results are discussed in terms of: (a) the implications for contrast sensitivity testing across orientations, (b) the basis for the oblique effect, and (c) a different type of evidence for a dichotomy among spatial-frequency channels that may reflect the distinction between X cells and Y cells or between the parvocellular and magnocellular systems. PMID- 1762880 TI - Origins of the proprioceptive function of vision: visual control of posture in one day old domestic chicks. AB - Recently hatched domestic chicks control their upright bipedal posture, at least in part, with respect to the flow of visual information at the retina, as do human infants when they first acquire control of the head, of sitting, and of standing. Some implications of the similarity of the proprioceptive function of vision in chicks and in humans for the origins and development of postural control are discussed. PMID- 1762881 TI - The spacing illusion: a spatial aperture problem? AB - A geometrical illusion in which the horizontal spacing between adjacent parallel lines in a row is underestimated when the lines are tilted away from vertical in a chevron configuration was investigated in two experiments. The perceived spacing was found to decrease as the tilt angle increased, consistent with the idea that separation judgements are influenced by the normal spacing between lines ie at right angles to the line orientation. It is proposed that this illusion reveals an analogue in spatial perception to the well-known aperture problem in motion perception. In establishing the separation of nearby or overlapping shapes in an image, the visual system cannot only rely upon the normal separation of contours belonging to each shape (as would be visible through small spatial apertures or receptive fields), since this varies with contour orientation. The system is therefore faced with a spatial aperture problem. The spacing illusion may arise because information usually available to solve the problem is absent in the illusion figure, or it may reflect a bias in favour of the orthogonal, which is adopted in the face of the ambiguity. PMID- 1762882 TI - Integration of form across saccadic eye movements. AB - To perceive a stable world, one must somehow be able to relate visual information from successive fixations. Little is known, however, about the nature of the integrative process. By using a task which requires the integration of spatial position information from different fixations, it is demonstrated that visual information from previous fixations is preserved in a world-centered representation which is precise enough to support judgements of geometric shape. It is also shown that successive views are aligned with respect to common visual features, indicating that visual stability may be normally accomplished by a visual matching strategy in combination with cancellation by an eye-position signal. PMID- 1762883 TI - Influence of physical and semantic information in a categorisation task of fragmented forms. AB - Two experiments were carried out to investigate the influence of structural and semantic information in the categorisation of visual forms. In experiment 1 the stimuli were pairs of 'well structured' or 'poorly structured' fragmented forms differing in structural properties including convexity, collinearity, and closure of the elements, and in their 'nameability'. The influence of structural and semantic information was tested by means of a task involving the presentation to both visual hemifields separately of stimuli having within-category physical similarity. For well structured forms, subjects were asked to judge if two sequentially presented forms belonged to the same semantic category. For poorly structured forms, subjects were required to decide if two stimuli belonged to the same previously learnt category of forms. For the two types of stimuli, one category was composed of physically similar items, and the other was composed of physically dissimilar items. The results show a marked advantage for the category composed of physically similar forms when the stimuli are well structured but no differences between the two categories when the stimuli are poorly structured. This suggests a facilitation in the computation of global shape information for forms having collinear and closed elements. The only effect of semantic information was a tendency towards a right visual field advantage for same category pairs of well structured forms. The pattern of results for well structured fragmented forms (experiment 1) and forms in which fragments had been joined in order to complete the contour (experiment 2) were similar, suggesting that structured incomplete forms can be processed in the same way as forms having a continuous contour. Hypotheses about the organisational processes of forms are proposed in the discussion. PMID- 1762884 TI - Thumb's rule tested: visual angle of thumb's width is about 2 deg. AB - Measures of the size of various hand parts and their viewing distance when held at arm's length were made on one hundred and eighteen undergraduate students. A simple rule of thumb can be confirmed: Visual angle of the width of the thumb held at arm's length is about 2 deg. The thumbnail subtends about 1.5 deg and the index fingernail about 1 deg in width, when both are held at arm's length. These figures are good approximations for males and females, although a significant, direct, linear relationship exists between hand-part size and the visual angle of the part at arm's length. PMID- 1762885 TI - Mandatory HIV testing of health care workers. PMID- 1762886 TI - Qualitative empirical nursing research. PMID- 1762887 TI - Continuing education--a professional mandate. PMID- 1762888 TI - Domestic violence 91-92: implications for nurses. PMID- 1762889 TI - [Scandinavian alcohol policy. Inconvenience or prevention?]. AB - Both the occurrence of alcohol-related disorders and the effect of alcohol control policies on the level of alcohol consumption are well documented. Experience in the absence of restrictions has shown that price control, age limits, restricted availability, and other measures in fact have significant effects. As alignment with the European Community will probably limit the possibility of using price as an instrument of alcohol control, it will be important to preserve other methods of minimising alcohol consumption, and to promote public understanding and support of general alcohol control measures. PMID- 1762890 TI - [Scandinavian alcohol policy and future Europe]. AB - Among the measures pertinent to Nordic alcohol policy neither age limits, information campaigns nor the issue of licences will be affected by a possible membership of EC. The Nordic countries stricter rules in this regard will be accepted. On the other hand it will probably be difficult to sustain the alcohol monopoly, the price policy, and the ban on advertisements. If the alcohol policy in the EC countries is imported to the Nordic area there is reason to believe that this will have dramatic consequences for the consumption of alcohol and alcohol-related problems in Finland, Iceland, Norway and Sweden. PMID- 1762891 TI - [NAD (Scandinavian Research Alcohol and Drugs)--important center for cross scientific contacts in the alcohol and drug field]. PMID- 1762892 TI - [Danish alcohol policy]. AB - The Danish alcohol policy is not as restrictive as in Sweden and Norway but based on information and taxes. The taxes on alcohol have now been reduced as a consequence of the establishment of the inner market in EEC. The expected higher consumption of alcohol will most likely increase the already high cost of health care and social welfare. PMID- 1762893 TI - [First-pass metabolism of alcohol and its clinical significance]. AB - The metabolism of alcohol also proceeds in other parts of the body as well as the liver. Some part of the alcohol consumed by mouth is metabolized chiefly through the alcohol-dehydrogenase (ADH) activity in the gastric membrane before it is taken up into the bloodstream. This significant first pass-metabolism of alcohol, particularly on a full stomach, protects the organism against high concentrations of alcohol. The first pass-metabolism is lower in women than in men. It is low in alcoholics too, presumably because of alcohol-related damage to the gastric membrane. Several drugs in common use reduce the ADH activity in the gastric membrane, a point it may be well to remember when treating patients who use alcohol. PMID- 1762894 TI - [Finland's Medical Society's action program. Assistance for physicians with an alcohol problem]. PMID- 1762895 TI - Women, youth and alcohol. PMID- 1762896 TI - [Munchausen syndrome. A rare condition requiring many resources]. AB - This syndrome is an infrequent, but dramatic disorder. The patients do intentionally produce or feign physical symptoms in order to assume a patient role without any other obvious gain. It also characterized by multiple admissions to different wards and hospitals over years. The disorder differs from the somatoform disorders by the voluntary produced symptomatology. From a psychiatric angle of view the possible comorbidity with personality disorders is highlighted. Medicolegal aspects of the disorder is also discussed, particularly the legitimacy of accepting these persons' status as patients. References are made to the man who has given the name to the syndrome; an eighteen century German baron whose tall tales from his military service were used as illustrations to the syndrome nearly one and a half century later. PMID- 1762897 TI - [Rehabilitation of stroke patients. Possibilities, duration and effect]. AB - A close relationship exists between the severity of a stroke and the functional level that can be obtained after rehabilitation. The goal of rehabilitation, therefore, should be based on the severity of the stroke. Remission mainly takes place (more than 80 per cent) within the first three months post stroke. Remission after six months is very rare. Age and side of hemiparesis do not seem to influence the effect of rehabilitation significantly. It is not elucidated whether the severity of the stroke influence the effect of rehabilitation. Most of the controlled and the randomized studies indicate that rehabilitation of stroke patients, especially in rehabilitation units, accelerate remission, reduces length of stay and gives rise to a lasting improvement of function. PMID- 1762898 TI - [Current therapeutic targeting possibilities in leukemia]. AB - Investigations on the configuration of immunoglobulin (Ig) and T-cell receptor (TCR) genes have become more and more widespread. Through these methods it is possible to identify malignant clones, which by a transforming event have been blocked in further differentiation but continued to proliferate. Such clonal expansions can be verified by the Southern Blotting procedure as differences in molecular weight between normal and rearranged DNA fragments. In the lymphatic disorders it is possible to assign the malignant clone to B cell lineage by rearrangement in the immunoglobulin light chain gene, while heavy chain and T cell receptor genes do not show consistency in lineage restriction. In a study on AML patients with solitary expression of the T-cell marker CD7 we have identified a similarity in TCR beta and delta gene configurations, indicating a correlation between etiology and genetic pattern. Such observations can contribute to an elucidation of the malignant blood-diseases and by that a better choice in therapy. PMID- 1762899 TI - [Treatment with inhalation therapy or tablets?]. PMID- 1762900 TI - Upstream box/TATA box order is the major determinant of the direction of transcription. AB - Mammalian gene promoters for transcription by RNA polymerase II are typically organized in the following order: upstream sequence motif(s)/TATA box/initiation site. Here we report studies in which the order, orientation and DNA sequences of these three elements are varied to determine how these affect polarity of transcription. We have constructed promoters with an 'octamer' upstream sequence ATTTGCAT (or its complement ATGCAAAT) in combination with several different TATA boxes and initiation (cap) sites, and tested these promoters in transfection experiments with cultured cells. TATA boxes derived from the adenovirus major late promoter (TATAAAA), immunoglobulin kappa light chain (TTATATA) and heavy chain (TAAATATA) promoter functioned equally well or even better when inverted. Only the beta-globin TATA box (CATAAAA) was poorly active when inverted. In addition, a symmetrical TATA box (TATATATA) derived from a casein gene was very active. Our results suggest that the asymmetry of most TATA boxes (consensus TATAAAA) is not a primary determinant of the polarity of transcription. We also found that the initiation (cap) site, which usually consists of an adenine embedded in a pyrimidine-rich region (PyPyCAPyPyPyPyPy), was permissive towards sequence alterations; even a randomly composed sequence worked well. However, an inverted, hence purine-rich, cap site reduced transcript levels to 1/7th, as did an oligo G sequence. Irrespective of the presence of a cap site, the configuration: 'TATA box/octamer' yielded a strong leftward, rather than rightward transcription. From this, we conclude that the polarity of transcription is primarily determined by the linear order of an upstream sequence relative to a TATA box, rather than by the individual orientations of either of these two elements. PMID- 1762901 TI - The role of two surface exposed loops in transcription activation by the Escherichia coli CRP and FNR proteins. AB - We have investigated a number of mutations that alter the ability of the E. coli transcription factors CRP and FNR to activate transcription. In CRP, some mutations at position 159 (H159L, H159I and delta 159) prevent transcription activation at a number of naturally-occurring and semi-synthetic CRP-dependent promoters. We suggest that some feature of the surface-exposed turn around residue 159 is recognised by RNA polymerase during transcription activation at these promoters. Mutations at position 52 increase CRP activity and reverse the effects of H159L and delta 159, most likely by creating a new contact with RNA polymerase. However this new contact only gives increased expression when the CRP binding site is located 41 1/2 base pairs upstream of the transcription start site and fails to reverse the effects of H159L and delta 159 at promoters where the CRP site is located further upstream. To explain our results we propose that the two surface-exposed turns around residues 52 and 159 contain elements that are potential RNA polymerase docking sites: in the CRP dimer these two active patches are located on adjacent faces of different subunits. FNR, a related transcription activator, contains amino acid sequences homologous to the CRP sequence around position 52. Mutations in this zone (from residues 81-88 in FNR) reduce expression from an FNR-dependent promoter without stopping FNR binding to its target. This defines a patch on FNR, which is homologous to the CRP surface exposed loop around position 52, which is involved in transcription activation, most likely by contacting RNA polymerase. PMID- 1762902 TI - Interaction of echinomycin with An.Tn. and (AT)n regions flanking its CG binding site. AB - We have prepared DNA fragments containing the sequences A15CGT15, T15CGA15 and T(AT)8CG(AT)15 cloned within the SmaI site of the pUC19 polylinker. These have been used as substrates in footprinting experiments with DNase I and diethylpyrocarbonate probing the effects of echinomycin, binding to the central CG, on the structure of the surrounding sequences. No clear DNase I footprints are seen with T15CGA15 though alterations in the nuclease susceptibility of surrounding regions suggest that the ligand is binding, albeit weakly at this site. All the other fragments show the expected footprints around the CG site. Regions of An and Tn are rendered much more reactive to DNase I and adenines on the 3'-side of the CG become hyperreactive to diethylpyrocarbonate. Regions of alternating AT show unusual changes in the presence of the ligand. At low concentrations (5 microM) cleavage of TpA is enhanced, whereas at higher concentrations a cleavage pattern with a four base pair repeat is evident. A similar pattern is seen with micrococcal nuclease. Modification by diethylpyrocarbonate is strongest at alternate adenines which are staggered in the 5'-direction across the two strands. We interpret these changes by suggesting secondary drug binding within regions of alternating AT, possibly to the dinucleotide ApT. DNase I footprinting experiments performed at 4 degrees C revealed neither enhancements nor footprints for flanking regions of homopolymeric A and T suggesting that the conformational changes are necessary consequence of drug binding. PMID- 1762903 TI - Echinomycin binding to alternating AT. AB - We have studied the binding of echinomycin to DNA fragments containing GC-rich regions flanked by blocks of alternating AT by DNase I footprinting and diethylpyrocarbonate modification. Regions of alternating AT flanking the sequences CCCG, CCGC, CGGC and GG show a four base pair DNase I cleavage pattern and reaction of alternate adenines with diethylpyrocarbonate. This pattern is strongest when the AT-block is immediately adjacent to the CpG ligand binding site. We explain these phenomena by suggesting that echinomycin binds to the dinucleotide step ApT in a cooperative fashion. The cooperative effects can be transmitted through the dinucleotide step GC but not CC or AA. No such repetitive patterns are seen with surrounding regions of (ATT).(AAT). Evidence is presented for secondary drug binding sites at CpC and TpG with weaker interaction at the CpG site within the hexanucleotide TTCGAA. PMID- 1762904 TI - DNA polymerase delta: gene sequences from Plasmodium falciparum indicate that this enzyme is more highly conserved than DNA polymerase alpha. AB - Genes encoding proteins homologous to the catalytic subunits of DNA polymerase alpha and delta have been cloned from the human malaria parasite Plasmodium falciparum. These are among the first cellular replicative DNA polymerase genes to be cloned and their sequences allow us to make new statements about the relative degrees of conservation of these two enzymes. The most important finding was that P. falciparum Pol delta showed considerable homology to the only other Pol delta enzyme for which published sequence is available, that of S. cerevisiae, displaying an overall amino acid identity of 45% and identity over a highly conserved central region of 59%. In contrast, the level of identity shown over the equivalent central region of Pol alpha between the P. falciparum and S. cerevisiae sequences is only 32%. The sequence data also allowed us to examine the degree of conservation in putative exonuclease domains of Pol delta. The Pol delta gene of P. falciparum maps to chromosome 10 and evidence is presented for the presence of different sized Pol delta mRNA's in the asexual and sexual erythrocytic stages of parasite development. PMID- 1762905 TI - Cloning and characterization of the rad4 gene of Schizosaccharomyces pombe; a gene showing short regions of sequence similarity to the human XRCC1 gene. AB - The rad4.116 mutant of the fission yeast Schizosaccharomyces pombe is temperature sensitive for growth, as well as being sensitive to the killing actions of both ultraviolet light and ionizing radiation. We have cloned the rad4 gene by complementation of the temperature sensitive phenotype of the rad4.116 mutant with a S. pombe gene bank. The rad4 gene fully complemented the UV sensitivity of the rad4.116 mutant. The gene is predicted to encode a protein of 579 amino acids with a basic tail, a possible zinc finger and a nuclear location signal. The amino terminal part of the predicted rad4 ORF contains two short regions of similarity to the C-terminal part of the human XRCC1 gene. Codon usage suggests that the gene is very poorly expressed, and this was confirmed by RNA studies. Gene disruption showed that the rad4 gene was essential for the mitotic growth of S. pombe. PMID- 1762906 TI - In the Escherichia coli lacZ gene the spacing between the translating ribosomes is insensitive to the efficiency of translation initiation. AB - We have constructed a series of 44 Escherichia coli strains in which the chromosomal region corresponding to the Ribosome Binding Site (RBS) of the lacZ gene, has been replaced by small DNA fragments harboring either RBSs from other genes, or artificial RBSs. The beta-galactosidase expression from these strains ranges from 1 to 130 per cent of that of the parental strain. Using this collection, we demonstrate here that strain-to-strain variations in expression are paralleled by nearly equivalent variations in lacZ mRNA content. We propose that, in this system, polarity and mRNA stability are tightly coupled to translation initiation, so that changes in RBS efficiency are detected mainly as changes in mRNA concentration rather than in the spacing between translating ribosomes. In addition, we show that the mRNA sequence immediately downstream from the initiator codon influences per se the lifetime of the lacZ mRNA. We discuss the mechanism of the interdependence between translation, transcription and degradation in this gene, and speculate about the general role of this interdependence in determining the expression of bacterial genes. PMID- 1762907 TI - Site-specific cleavage of natural mRNA sequences by newly designed hairpin catalytic RNAs. AB - The negative strand of tobacco ringspot virus satellite RNA is a self-cleaving RNA. Its catalytic domain and substrate domain have been identified, and the catalytic domain has been named hairpin catalytic RNA. Here we report the construction of a plasmid containing a modified hairpin catalytic RNA sequence that can be transcribed in vitro. Because this plasmid has two specific restriction enzyme recognition sites at both ends of the substrate binding site in the catalytic RNA sequence, it is possible to construct new plasmids by substituting different sequences in the substrate binding site. Using this plasmid, synthetic DNA, and in vitro transcription, we obtained three ribozymes designed to cleave Escherichia coli prolipoprotein signal peptidase (lsp) mRNA at specific sites. All three ribozymes cleaved the lsp mRNA sequence in vitro at the specific sites, and two of them cleaved it efficiently. Kinetic analyses showed that one had a higher kcat/Km value than that of the well-known hammerhead ribozyme. Problems associated with attaining the goal of expressing these ribozymes in vivo also are discussed. PMID- 1762908 TI - Apolipoprotein B mRNA sequences 3' of the editing site are necessary and sufficient for editing and editosome assembly. AB - Apolipoprotein B (apoB) mRNA is edited in rat liver and intestine through the direct conversion of cytidine to uridine at nucleotide 6666. Recently, we have proposed the 'Mooring Sequence' model, in which editing complexes (editosomes) assemble on specific apoB mRNA flanking sequences to direct this site-specific editing event. To test this model, apoB mRNA deletion and translocation mutants were constructed and analyzed. Specific sequences 3' of the editing site were absolutely required for editing, while specific sequences and bulk RNA 5' of the editing site were required for efficient editing. Translocation of apoB 3' flanking sequences induced editing of an upstream cytidine, demonstrating that 3' sequences are necessary and sufficient to direct editing in vitro. 3' flanking sequences were also shown to be necessary and sufficient for editosome complex assembly. These data provide strong support for a 'Mooring Sequence' model in which 3' apoB flanking sequences direct editosome assembly and subsequent editing in vitro, while 5' flanking sequences enhance these functions. PMID- 1762909 TI - cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes. AB - The HMGI-C protein is a nuclear phosphoprotein expressed at high levels in transformed cells. The cDNA encoding the mouse protein has been isolated and the sequence of the encoded protein shows that it is related to the HMGY and I proteins, proteins which bind in the minor groove of DNA containing stretches of A and T. The HMGI-C protein has three short highly basic domains, an acidic C terminal domain, and potential CDC2/p34 and casein kinase II phosphorylation sites. Analysis of mRNA levels demonstrate that the HMGI-C gene is not expressed in a variety of mouse tissues but is expressed in Lewis lung carcinoma cells. PMID- 1762910 TI - Presence of regulatory sequences within intron 2 of the mouse thymidine kinase gene. AB - The intron 2 of the murine thymidine kinase (TK) gene was observed to contain two DNase hypersensitive site. In vitro footprinting experiments indicated specific binding sites for nuclear proteins which were characterized within the sequence of intron 2. Two GC boxes (binding sites for transcription factor SP1) and two new protein binding regions, one at the promoter proximal end of intron 2, the other one close to the border to exon 3 were found. Oligonucleotides were synthesized comprising the two new binding sites and were shown in gel mobility shift experiments to be capable of forming specific complexes with nuclear proteins. These proteins are present in growing as well as in quiescent cells suggesting that the sites described here do not contribute to growth regulation of TK expression. That they might play a role in upregulation of TK expression is, however, indicated by the results of CAT assays in which inclusion of downstream sequences of the TK gene containing parts or all of intron 2 were found to positively modulate the activity of the TK promoter. PMID- 1762911 TI - Probing of DNA structure with osmium tetroxide,2,2'-bipyridine. Adduct-specific antibodies. AB - Antibodies against DNA modified with a single-strand selective probe, OsO4 in complex with 2,2'-bipyridine (Os,bipy), were raised in rabbits. These antibodies were fractionated using affinity column chromatography and fractions S89-II and S89-III characterized as highly specific for DNA-Os,bipy adduct with no cross reactivity to at least 1000-fold excess of unmodified DNA, RNA and Os,bipy modified and unmodified proteins. Cross-reactivity to Os,bipy-modified RNA was very small. S89-II showed no cross-reactivity to DNA modified with OsO4 complexed with tetramethylethylenediamine or with bathophenanthroline disulphonic acid and to DNA oxidized with KMnO4. It cross-reacted, however, with DNA modified with OsO4,1,10-phenanthroline complex. The limit of detection of immunodot-blot analysis of extensively Os,bipy-modified DNA was below 0.5 pg. Small extent of Os,bipy-modification of supercoiled and linearized plasmids can be detected by DNA gel retardation and immunoblotting techniques. E. coli cells contain DNA regions in which bases are accessible to the single-strand selective probe. PMID- 1762912 TI - Requirement of protein factors and ATP for the disassembly of the spliceosome after mRNA splicing reaction. AB - Pre-mRNA splicing reaction occurs in a large ribonucleoprotein complex called the spliceosome. After the splicing reaction, the spliceosome is disassembled to release the splicing products including spliced mRNA. Here we show that protein factors in a HeLa nuclear extract or a DEAE-cellulose fraction as well as ATP are required to release the splicing products form the spliceosome in which the splicing reaction has already completed. PMID- 1762913 TI - Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. AB - Dispersed repetitive DNA sequences have been described recently in eubacteria. To assess the distribution and evolutionary conservation of two distinct prokaryotic repetitive elements, consensus oligonucleotides were used in polymerase chain reaction [PCR] amplification and slot blot hybridization experiments with genomic DNA from diverse eubacterial species. Oligonucleotides matching Repetitive Extragenic Palindromic [REP] elements and Enterobacterial Repetitive Intergenic Consensus [ERIC] sequences were synthesized and tested as opposing PCR primers in the amplification of eubacterial genomic DNA. REP and ERIC consensus oligonucleotides produced clearly resolvable bands by agarose gel electrophoresis following PCR amplification. These band patterns provided unambiguous DNA fingerprints of different eubacterial species and strains. Both REP and ERIC probes hybridized preferentially to genomic DNA from Gram-negative enteric bacteria and related species. Widespread distribution of these repetitive DNA elements in the genomes of various microorganisms should enable rapid identification of bacterial species and strains, and be useful for the analysis of prokaryotic genomes. PMID- 1762914 TI - Constitutive expression of the urokinase plasminogen activator gene in murine RAW264 macrophages involves distal and 5' non-coding sequences that are conserved between mouse and pig. AB - The 5' flanking regions of the mouse and pig urokinase plasminogen activator (uPA) genes were sequenced and sequence homology interrupted by repeat elements was found to extend to -4.6kb in pig and -6.6kb in mouse. A transient transfection procedure was devised for the murine macrophage cell line RAW264. Pig uPA promoter-CAT constructs were more active than mouse constructs in this assay. This contrast may involve sequence differences within 100 bp of the transcription start site. The selective deletion of distal regions of the promoter (greater than 2.6 kb upstream), and of a conserved element, 5' AGGAGGAAATGAGG-TCA-3' around -2 kb greatly reduced the activity of reporter constructs in RAW264 cells. Electrophoretic mobility shift assays using the latter sequence identified a single nuclear protein complex. This element has been referred to as PEA3/AP1-like, but the complex did not comigrate with either AP1 or known proteins that bind polypurines (including the macrophage-specific factor PU-1) and was not competed by AP1 or polypurine oligonucleotides. uPA promoters contain multiple AP1 and AP2-like DNA sequences, which were recognised by nuclear proteins expressed constitutively in RAW264 cells. They also contain multiple binding sites for NF kappa B but activated NF kappa B was not expressed in RAW264 cells. The conserved, transcribed 5' non-coding sequences were also required for maximal gene expression. Hence, the uPA promoter contains multiple weak cis-acting elements distributed over 7.0 kb 5' to the translation start site. PMID- 1762915 TI - An efficient, sequence-specific method for crosslinking complementary oligonucleotides using binuclear platinum complexes. AB - The binuclear PtII complexes [(trans-Pt(NH3)2Cl)2 (NH2(CH2)nNH2)]Cl2 (n = 4, 5 or 6), crosslink oligodeoxynucleotide-5'-phosphorothioates rapidly, specifically and efficiently to complementary single-stranded oligodeoxynucleotide targets. In the case that we investigated in detail, the most abundant crosslink is formed to the G residue complementary to the 5'-terminal C residue of the phosphorothioate. Less efficient crosslinking occurs to many other residues of the target. The same PtII complexes also bring about crosslinking efficiently to the polypurine tract in triple-helical DNA. PMID- 1762916 TI - Purification and substrate specificity of a T4 phage intron-encoded endonuclease. AB - The T4 phage td intron-encoded endonuclease (I-Tev I) cleaves the intron-deleted td gene (td delta I) 23 nucleotides upstream of the intron insertion site on the noncoding strand and 25 nucleotides upstream of this site on the coding strand, to generate a 2-base hydroxyl overhang in the 3' end of each DNA strand. I-Tev I 157, a truncated form in which slightly more than one third (88 residues) of the endonuclease is deleted, was purified to homogeneity and shown to possess endonuclease activity similar to that of I-TEV I, the full-length enzyme (245 residues). The minimal length of the td delta I gene that was cleaved by I-Tev I and I-Tev I-157 has been determined to be exactly 39 basepairs, from -27 (upstream in exon1) to +12 (downstream in exon2) relative to the intron insertion site. Similar to the full-length endonuclease, I-Tev I-157 cuts the intronless thymidylate synthase genes from such diverse organisms as Escherichia coli, Lactobacillus casei and the human. The position and nature of the in vitro endonucleolytic cut in these genes are homologous to those in td delta I. Point mutational analysis of the td delta I substrate based on the deduced consensus nucleotide sequence has revealed a very low degree of specificity on either side of the cleavage site, for both the full-length and truncated I-TEV I. PMID- 1762917 TI - Structural elements in the N-terminal half of transcription factor IIIA required for factor binding to the 5S RNA gene internal control region. AB - Zinc binding domains and the conserved Thr-Gly-Glu-Lys (TGEK) tetrapeptide in the N-terminal half of transcription factor IIIA (TFIIIA) were subjected to in vitro mutagenesis to biochemically assess their role in factor interaction with the 5S gene internal control region (ICR). TFIIIA containing a Leu in place of His33 in the Cys2His2 zinc binding site of finger I lost the ability to protect the entire 5S RNA gene ICR (nucleotides +96 to +43) from DNase I digestion. Thus, mutation of one potential zinc ligand in the N-terminal finger inhibited specific DNA binding by the N-terminal as well as downstream fingers. Cooperativity apparently exists among TFIIIA zinc fingers in metal binding/finger folding and DNA binding. Substituting a Ser for Gly69 or a Glu for Lys 71 in the conserved TGEK tetrapeptide in finger II of TFIIIA resulted in the loss of DNA binding. A Gly dependent bend structure and a terminal positive charge in this tetrapeptide are important for TFIIIA interaction with DNA. Whereas TFIIIA with a Ser substituted for Cys20 in finger I (proposed zinc ligand) did not protect the ICR from DNase I digestion, TFIIIA containing a Ser substituted for Cys35 (not a proposed zinc ligand) retained the ability to bind the ICR. When Cys112 or Cys 164 (proposed zinc ligands in fingers IV and VI) were replaced by Ser, the DNase I footprint patterns afforded by the respective mutant proteins were similar, protection on the ICR from about nucleotides +96 up to +78. A similar pattern was obtained with a TFIIIA mutant in which fingers V, VI, VII, and a portion of VIII were deleted. Maintenance of zinc coordination spheres in necessary for DNA binding by downstream fingers. The six fingers comprising the N-terminal half of TFIIIA appear to act in two groups of three with binding of the second group dependent upon initial binding of the N-terminal group to the +90 to +80 region of the 5S gene ICR. PMID- 1762918 TI - Cloning and physical mapping of DNA sequences encompassing a region in N-myc amplicons of a human neuroblastoma cell line. AB - Cloning and physical mapping of DNA sequences encompassing N-myc amplicons of a human neuroblastoma cell line were done. A number of lambda phage clones within this region were isolated using the probes prepared by the phenol emulsion reassociation technique. Based on the restriction mapping, they were integrated into 8 contigs with sizes of 25-60 kb which, in total, encompassed a 330 kb region. Several amplicons, 100, 420, 480 and 520 kb in size as a Notl fragment, were identified using hexagonal field gel electrophoresis, and the contigs were assigned in these Notl fragments. The region encompassed by the contigs was equivalent to some 60-80% of the amplicons identified as a Notl fragment. In order to compare the amplified regions flanking the N-myc gene among the cell lines, the phage clones to cover the whole contigs were used for hybridization as a probe. The results showed that the portions of the whole contigs ranging 18-45% were also amplified in the cell lines examined. These results allowed us to identified the 'rearranged sites' which were rather evenly distributed, one at every 40 kb, through the contigs. These observations lead to the idea that an amplified DNA domain is constructed after the multiple rearrangements and then increases in number, finally resulting in the formation of subsets of amplicons with sequence homogeneity. PMID- 1762919 TI - A novel translation initiation region from Mycoplasma genitalium that functions in Escherichia coli. AB - The tuf gene of Mycoplasma genitalium uses a signal other than a Shine-Dalgarno sequence to promote translation initiation. We have inserted the translation initiation region of this gene in front of the Escherichia coli lacZ gene and shown that it is recognized by the translational machinery of E. coli; the signal operates in vivo at roughly the same efficiency as a synthetic Shine-Dalgarno sequence. The M. genitalium sequence was also used to replace the native translation initiation region of the cat gene. When assayed in E. coli, the M. genitalium sequence is equivalent to a Shine-Dalgarno sequence in stimulating translation of this mRNA also. Site-directed mutagenesis enabled us to identify some of the bases that comprise the functional sequence. We propose that the sequence UUAACAACAU functions as a ribosome binding site by annealing to nucleotides 1082-1093 of the E. coli 16S rRNA. The activity of this sequence is enhanced when it is present in the loop of a stem-and-loop structure. Additional sequences both upstream and downstream of the initiation codon are also involved, but their role has not been elucidated. PMID- 1762920 TI - Transcription factor binding and spacing constraints in the human beta-actin proximal promoter. AB - The human beta-actin promoter, including its 5' flanking region and 5' untranslated region, is ubiquitously active in mammalian cells in culture. In this report we investigated the transcriptional activity of, and the protein-DNA interactions that occur within, the proximal region of the human beta-actin promoter. Efficient beta-actin promoter activity in transfected human HeLa cells requires only 114bp of 5' flanking sequences. Two of the cis-actin regulatory elements within this region of the beta-actin promoter, the CCAAT box and proximal CCArGG box, are specific in vitro binding sites for the transcription factors, nuclear factor Y (NF-Y) and serum response factor (p67SRF), respectively. These two elements are required together to stimulate in vivo transcription from the homologous as well as a heterologous promoter. Finally, a particular spatial alignment between the CCAAT box and proximal CCArGG box is required for trans-activation in vivo. The above provides strong evidence for a functional interaction between NF-Y and p67SRF when bound to their respective binding sites in the beta-actin promoter. PMID- 1762921 TI - RNA editing makes mistakes in plant mitochondria: editing loses sense in transcripts of a rps19 pseudogene and in creating stop codons in coxI and rps3 mRNAs of Oenothera. AB - An intact gene for the ribosomal protein S19 (rps19) is absent from Oenothera mitochondria. The conserved rps19 reading frame found in the mitochondrial genome is interrupted by a termination codon. This rps19 pseudogene is cotranscribed with the downstream rps3 gene and is edited on both sides of the translational stop. Editing, however, changes the amino acid sequence at positions that were well conserved before editing. Other strange editings create translational stops in open reading frames coding for functional proteins. In coxI and rps3 mRNAs CGA codons are edited to UGA stop codons only five and three codons, respectively, downstream to the initiation codon. These aberrant editings in essential open reading frames and in the rps19 pseudogene appear to have been shifted to these positions from other editing sites. These observations suggest a requirement for a continuous evolutionary constraint on the editing specificities in plant mitochondria. PMID- 1762922 TI - Rat elongation factor 1 alpha: sequence of cDNA from a highly metastatic fos transferred cell line. PMID- 1762923 TI - Complete nucleotide sequence of Friend murine leukemia virus, strain FB29. PMID- 1762924 TI - A conserved pseudoknot in telomerase RNA. PMID- 1762925 TI - The DNA polymerase gene from the hyperthermophilic marine archaebacterium, Pyrococcus furiosus, shows sequence homology with alpha-like DNA polymerases. PMID- 1762926 TI - Squashes of plant tissue as substrate for PCR. PMID- 1762927 TI - A U1 snRNA binding site improves the efficiency of in vitro pre-mRNA splicing. PMID- 1762928 TI - A simple method for sequencing the complementary strand of ssDNA from M13 clones. PMID- 1762929 TI - Binding of hairpin and dumbbell DNA to transcription factors. PMID- 1762930 TI - Sequencing self-ligated PCR products using 3' over-hangs generated by specific cleavage of dUTP by uracil-DNA glycosylase. PMID- 1762931 TI - Heat inactivation of DNA ligase prior to electroporation increases transformation efficiency. PMID- 1762932 TI - An STS in the human oct-1 gene located on chromosome 1. PMID- 1762933 TI - Dinucleotide repeat polymorphisms at the D16S164, D16S168 and D16S186 loci at 16q21-q22.1. PMID- 1762934 TI - Dinucleotide repeat polymorphism in the human SRC gene on chromosome 20. PMID- 1762935 TI - Dinucleotide repeat polymorphism at the human tyrosinase gene. PMID- 1762936 TI - Dinucleotide repeat polymorphism at the FTHPI locus of chromosome 6. PMID- 1762937 TI - Dinucleotide repeat polymorphism at the D5S260 locus on chromosome 5q. PMID- 1762938 TI - Dinucleotide repeat polymorphism in D20S17 (CRI-L127). PMID- 1762939 TI - Properties of a highly polymorphic locus (D2S92) located in the telomeric region of chromosome 2. PMID- 1762940 TI - G/A polymorphism in an intron of the fibrillin gene FBNI. PMID- 1762941 TI - An Alu polymorphism intragenic to the TP53 gene. PMID- 1762942 TI - A microsatellite polymorphism at the D3S11 locus. PMID- 1762943 TI - Dinucleotide repeat polymorphism in the human angiotensinogen gene. PMID- 1762944 TI - Dinucleotide repeat polymorphism in the human coagulation factor XI gene, intron B (F11), detected using the polymerase chain reaction. PMID- 1762945 TI - Dinucleotide repeat polymorphism in the human alpha-cardiac actin gene, intron IV (ACTC), detected using the polymerase chain reaction. PMID- 1762946 TI - Tetranucleotide repeat polymorphism at the human beta-actin related pseudogene 2 (ACTBP2) detected using the polymerase chain reaction. PMID- 1762947 TI - Dinucleotide repeat polymorphism at the D11S436 locus. PMID- 1762948 TI - A sequence polymorphism in the human peripherin/RDS gene. PMID- 1762949 TI - Polymorphism in the protein C gene detected by denaturing gradient gel electrophoresis. PMID- 1762951 TI - M1: principles of management. Part (i): Are you a manager? PMID- 1762952 TI - School nurses should be able to dispense lotion for head lice. PMID- 1762953 TI - Film test. PMID- 1762950 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1762954 TI - Not waving ... but drowning. PMID- 1762955 TI - Patients' rights? PMID- 1762956 TI - The latest gag? PMID- 1762957 TI - Silent suffering. PMID- 1762958 TI - Elected to counsel. PMID- 1762959 TI - Stress--pressure point. PMID- 1762960 TI - Stress--something had to give. PMID- 1762961 TI - Management--taking stock. PMID- 1762962 TI - Education. Student-led maternity care. PMID- 1762963 TI - Moonstruck. PMID- 1762965 TI - Elderly people's view of nursing reforms. PMID- 1762964 TI - Support for staff in community units. PMID- 1762966 TI - Unfairly judged. PMID- 1762967 TI - Arts in action. Special effects. PMID- 1762968 TI - Systems of life. Reproductive system--Part 3. PMID- 1762969 TI - Child health--dental plates for oral feeding. PMID- 1762970 TI - Psychiatric help needed for people with HIV. PMID- 1762971 TI - Pain as a metaphor for illness. Part I: Impact of cancer pain on family caregivers. AB - While previous research has focused on patients' or professional caregivers' perspective of pain, this study describes cancer pain from the family caregivers' perspective. Chronic pain, which is associated with malignant disease, produces an intense burden on the patient as well as on the entire family. This qualitative study included 85 family caregivers of patients with cancer pain. Data were collected using an interview guide, and verbatim responses were analyzed for themes. The results identified four themes surrounding family descriptions of pain (anatomic descriptions, hidden pain, family fear and suffering, and overwhelming/unendurable pain) and three themes surrounding family experience of pain (helplessness, coping by denying feelings, and a wish for death). This study documents the important role that family members play in cancer treatment. If the number of patients receiving care in the home from family members continues to grow, this role will become even more important. Part I of this two-part paper focuses on the impact that cancer pain has on family caregivers and concludes that pain does have a tremendous impact on the family because it is perceived as a metaphor of progressive illness and death. PMID- 1762972 TI - Pain as a metaphor for illness. Part II: Family caregivers' management of pain. AB - Changes in the healthcare system have made the patient's home the primary site of cancer care. Family members, already burdened with the psychological impact of having a loved one with cancer, take on caregiving roles to meet the multiple and complex needs of the patient. Part I of this two-part article focused on family caregivers' descriptions of the patients' pain and the impact of this pain on caregivers. A model of the Caregiver Experience of Pain is provided along with implications for future inquiry and clinical practice. Themes identified in caregiver roles in medication administration included deciding what to give, deciding when to give, night duty, reminding/encouraging, keeping records, fear of addiction, and doing everything. Caregiver roles in nondrug interventions included positioning/mobility, massage, use of ointments/lotions, cold, heat, being there through touch, avoiding touch, and talk and other distractions. Caregiver perceptions of what doctors or nurses could do better included themes of being there, explain, be honest/listen, addiction concern, and giving medication. Caregiver questions included areas of future, understanding why, death, concern about medications, and fear about what to do at home. The study results offer important suggestions for oncology nurses in supporting family caregivers in the management of the patient in pain. PMID- 1762973 TI - The therapeutic use of music for cancer-related pain. AB - The purpose of this experimental crossover study was to evaluate to what extent the therapeutic use of music would decrease pain in patients with cancer who were receiving scheduled analgesics. Baseline data were collected for three days. Subjects then were assigned randomly to listen to their preference of seven types of relaxing music or a control (a 60-cycle hum) twice daily for three days. Then they crossed over into the alternate group for the next three days. Finally, each subject returned to a follow-up baseline period. Pain, the dependent variable, and mood, which was proposed as an intervening variable, were measured by visual analogue scales. The convenience sample included 15 outpatients with cancer, 12 female and 3 male, ages 20 through 87. Results of the McGill Pain Questionnaire (MPQ), a reliable and valid multidimensional instrument administered upon entry into the study, indicated that the study sample was comparable to other samples of patients with cancer who were in pain. There was an inconsistent relation between pain and mood. The effect of the music on pain varied by individual; 75% had at least some response and 47% had a moderate or great response. Multivariate Analysis of Variance (MANOVA) indicated a statistically significant decrease in pain from using either the music or sound, but there was no effect on mood. Although the mean percentage of change in pain for music was twice that for sound, the results did not differ statistically. The findings support the use of music as an independent nursing intervention to relieve pain. PMID- 1762974 TI - Appraisal and caregiving burden in family members caring for patients receiving chemotherapy. AB - The purposes of this exploratory study of 49 family caregivers of patients receiving chemotherapy were to describe the time and difficulty associated with caregiving tasks, examine caregivers' appraisals of their situations, and to explore what variables are predictive of caregiver mood. Measures used in this study included the Caregiving Burden Scale, Appraisal of Caregiving Scale, Family Hardiness Index, and an abbreviated form of the Profile of Mood States. Multiple regression was used to examine predictive relationships. The 25 women and 24 men reported spending the most time giving emotional support and assisting with household tasks, errands, and transportation. Giving emotional support was the most time-consuming and difficult task; therefore, it received the highest burden score. Burden was predicted by level of patient dependency. Caregiving burden, family hardiness, and caregiver health predicted 50% of the variance in negative appraisal of caregiving. Negative appraisal and age of the caregiver explained 49% of the variance in mood disturbance. Findings suggest that caregivers' appraisals of their situations may mediate the effects of illness and contextual factors on caregiver outcomes and that family hardiness is an important caregiver resource. PMID- 1762975 TI - A comparison of transparent adherent and dry sterile gauze dressings for long term central catheters in patients undergoing bone marrow transplant. AB - Patients undergoing bone marrow transplant (BMT) are at great risk of infection and sepsis. Long-term central catheters (LTCCs), required for IV therapy, can be a portal of entry for infectious agents. This randomized, prospective study compared two types of catheter dressings in 98 patients undergoing BMT: a dry sterile gauze dressing (DSGD) changed daily and a transparent adherent dressing (TAD) changed every four days. Study outcomes included incidence and severity of local and systemic complications, patient assessment of comfort, and calculation of nursing time. One case of catheter-related infection occurred during the study. No significant differences existed between the two dressings in the incidence of positive skin cultures or local complications with the exception of skin irritation. The TAD caused less skin irritation, was preferred by patients, cost less, and required less nursing time. The findings indicate that TADs provide a safe, comfortable, and cost-effective alternative to DSGDs for patients undergoing BMT and receiving antibiotic support during aplasia. PMID- 1762976 TI - Laughter therapy for patients with cancer. AB - Humor is an important part of life. Care should be taken to ensure that humor persists even during the bleakest times for patients, families, and medical personnel. Laughter eases the mind, defuses tension among people, and has positive physiologic effects on patients. Facilitated nursing intervention with humor helps to inject this important facet of life into difficult scenes. One successful approach to introducing humor into the hospital setting is a hall roving "Laugh Mobile." Its humorous novelties, books, and films help divert the attention of suffering patients to lighter thoughts. PMID- 1762977 TI - The practice of breast self-examination among older women. AB - Mammography, professional breast examination (PBE), and breast self-examination (BSE) are viewed as very important screening techniques for the early detection of breast cancer. Mammography and PBE are performed on a routine basis at healthcare facilities, while BSE can be performed in the privacy of the home. The self-care practice of monthly BSE is important for women of all ages. Older women often feel unsure about their ability to perform BSE properly, and many know very little about this self-care practice. The purpose of this research study was to explore the validity of teaching older women the practice of BSE using the method of return demonstration. The inclusion of actual practice opportunities with models into teaching sessions resulted in the older women feeling more confident about their ability to perform BSE. PMID- 1762978 TI - Teaching women about mammography through use of a brochure. AB - This paper describes the development and use of a brochure intended to educate women about the nature and benefits of mammography. This brochure, which is presented in its entirety, has several unique features. It addresses the myths associated with mammograms and includes a visual depiction of the difficult-to understand concept of relative difference with respect to size of breast lesions. PMID- 1762979 TI - 1991 Oncology Nursing Society Research Priorities Survey. AB - Documenting current research priorities is an ongoing process that is important to furthering the research agenda of oncology nursing. The purpose of this study was to update and partially replicate previous Oncology Nursing Society (ONS) research priorities surveys. Questionnaires were sent to a convenience sample of 429 ONS members involved in research or in ONS leadership. The response rate was 70% (N = 310). Respondents identified a combination of clinical problems, research issues, and cancer care economic factors among their top 10 research priorities. Quality of life and symptom management consistently were ranked as the highest priority items across all three methods used to rank-order the items. Respondents also provided suggestions for future ONS/Oncology Nursing Foundation small grants and for expansion of current ONS research activities. These findings provide direction for the focus of oncology nursing research by suggesting topics for research, by identifying areas that require additional research funding, by recommending new research activities for ONS, and by promoting research as the basis for oncology nursing practice. PMID- 1762981 TI - Assessing master's programs in oncology nursing. PMID- 1762980 TI - Performance of current procedural terminology codes by oncology nurses: a report to the ONS board of directors. AB - At the request of the ONS Board of Directors, a survey was conducted to determine the degree to which oncology nurses performed services listed in the Physicians Current Procedural Terminology manual--services for which physicians are reimbursed. Using a format modeled on a similar study of nurses in general, 100 randomly selected ONS members were asked to describe the degree to which they performed a list of 90 coded procedures compiled by four oncology nurse experts. Response rate was 43%. Respondents, who were representative of the ONS membership on all demographic variables except education, performed an average of 32 of the procedures with very little, if any, direct physician supervision. Study results reflect trends found among nurses in general and raise important questions about patterns of reimbursement and healthcare delivery. PMID- 1762982 TI - Survey of graduate programs in cancer nursing. PMID- 1762983 TI - Patient information survey: meeting the psychosocial needs of the patient with cancer. PMID- 1762984 TI - Do not resuscitate: facilitating communication for patients with cancer followed in ambulatory care. PMID- 1762985 TI - Development of a self-contained chemotherapy delivery system. PMID- 1762986 TI - Helpful hints for patients who have undergone an ostomy. PMID- 1762987 TI - Nizoral and stomatitis cocktails may not mix. PMID- 1762988 TI - Central venous catheter pouch. PMID- 1762989 TI - Accumulation and release of adrenaline, and the modulation by adrenaline of noradrenaline release from rabbit blood vessels in vitro. AB - The accumulation of (-)-3H-adrenaline (3H-A) by rabbit isolated aorta was studied. In all experiments, monoamine oxidase and catechol-O-methyltransferase were inhibited by treatment with pargyline and 3',4'-dihydroxy-2-methyl propiophenone, respectively. The relationship between the accumulation of 3H derived from 3H-A and the duration of incubation was linear. The 3H-accumulation after 3 h incubation was 22.5 ml/g. In reserpine-treated tissue, the 3H accumulation levelled off after 30 min and was 8.5 ml/g after 3 h. The concentration of 3H-A or (-)-3H-noradrenaline (3H-NA) and the 3H-accumulation (ml/g) were inversely related. At 10(-8) M, the 1-hour accumulation of 3H derived from 3H-A and 3H-NA was 7.8 and 15.2 ml/g, respectively. With increasing concentrations the accumulation values approached each other. The accumulation of 3H derived from 3H-A by reserpine-treated tissue also showed an inverse relationship with concentration. The accumulation of 3H derived from 3H-A was dependent on the bath temperature. Storage of tissue (0-5 days in salt solution without equilibration with 95% O2/5% CO2; 4 degrees C) did not affect the accumulation of 3H derived from 3H-A. Thereafter (7-14 days), the accumulation decreased. The inhibitory potency (IC50; -log M) of desipramine, cocaine, propranolol, isoprenaline, and normetanephrine on accumulation of 3H derived from 3H-A was found to be 8.26; 6.50; 5.48; 4.88, and 4.02, respectively. The maximal degree of inhibition was almost the same for these drugs, while that of clonidine and corticosterone was 50 and 20%, respectively. In the presence of desipramine, either clonidine, corticosterone or isoprenaline reduces the accumulation of 3H derived from 3H-A. Ouabain and iodoacetic acid, but not sodium cyanide and 2,4 dinitrophenol, reduced the accumulation of 3H derived from 3H-A. Anoxia (95% N2/5% CO2; 37 degrees C; 1-24 h) did not alter the accumulation of 3H derived from 3H-A. Glucose deprivation alone or combined with anoxia markedly reduced the 3H-accumulation. The release of 3H-A from rabbit isolated aorta was studied. This release was compared with that of 3H-NA. The stimulation-evoked 3H-overflow from aorta preloaded with 3H-A decreased with repeated stimulation. In contrast, prestimulation enhanced subsequent stimulation-evoked 3H-overflows. For both 3H amines, the 3H-overflow increased concomitantly to the same degree with the number of pulses. The time course of 3H-overflows with either 3H-A or 3H-NA was compared.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1762990 TI - [Methods for the prevention of psychologic developmental disorders within the scope of early childhood education--experiences in an American parent-child center]. AB - Preventive methods for the work with children and parents are presented by the example of a mental health prevention center, where the early development of children is carefully attended on the basis of psychoanalysis and own movement studies. Besides a child-centered setting and multifarious ways of fostering the child's creative expression the emphasis is laid on methods helping to mediate between parents and child in everyday life, as well as methods supporting the child's ego to enable it to cope with future traumatic events. PMID- 1762991 TI - [Familial reality construction. On dealing with intrafamilial realization processes in psychodiagnostic and psychotherapeutic contexts]. AB - Psychodynamic processes are connected to relationship-psychological and family dynamic phenomena in varied ways. Especially the processes of forming judgments and coming to realizations in the family influence the individual psychodynamics greatly. In these processes characteristics, purposes, roles and pathologies are ascribed to the individual family member. In this article these processes will be clearly shown with casuistic material. After this the author will clarify the theoretical relationship between the various levels of description which are the result of examining intrapsychic and family dynamic questions. PMID- 1762992 TI - [Documentation of child psychotherapy individual treatment--development of a protocol record]. AB - A record schedule is presented which serves as a documentation of single treatments in child therapy containing: course of session, playing behaviour, and psychodynamics. PMID- 1762993 TI - [Individual help for children with developmental difficulties in child day care centers of Stuttgart]. PMID- 1762994 TI - Stress revisited. 2. Systemic effects of stress. PMID- 1762995 TI - Recent advances in the assessment of lung function in infants. PMID- 1762996 TI - [13th annual meeting for Pediatric Pneumology. Dresden 21-23 March 1991]. PMID- 1762997 TI - [Determination of respiratory system compliance from resonance frequency--animal experiment]. AB - 10 anaesthetized and tracheotomized rabbits were used to test the possibility for calculation of total respiratory system compliance from resonance frequency (CR). Reference values were obtained by inflation method compliance (CI). A new servocontrolled infant ventilator was used with an integrated negative ventilator resistance mode for resistive unloading of combined resistances of lung, endotracheal tube and ventilator. This evoked oscillation at resonant frequency. By analogy with electrical circuit theory compliance was calculated as follows: CR = 1/(4 pi 2 x square root I.RF2). Pairs of CI and CR values were obtained from each animal during spontaneous breathing, after pancuronium relaxation and after surfactant depletion by lavage. There was found a significant linear correlation between CR and CI values (CR = 1.1 x CI-0.74; r = 0.97). PMID- 1762998 TI - [Dexamethasone in the treatment of bronchopulmonary dysplasia]. AB - Dexamethasone has been reported to benefit premature infants with bronchopulmonary dysplasia. 13 ventilator-dependent premature infants (birth weight 780-1270 g) with chronic lung disease received dexamethasone 0.5 mg/kg/day with tapering doses over 3 weeks. Dexamethasone therapy was associated with a temporary increase in urine output and blood pressure. All infants showed a significant fall in oxygen requirement and an increase of total pulmonary compliance during the first week. The endotracheal tube was successfully removed in all infants with Northway stage I/II BPD within the first week of treatment and no infant relapsed. But in Northway stage III/IV, only 2/9 infants could be weaned from the ventilator during the first course of treatment and in the majority treatment led only to a temporary improvement of pulmonary status. In parallel to the improvement of lung function we found in 7 infants a decrease of the total cell counts, the ratio PMN/macrophages and albumin in relation to urea in the bronchial lavages with a secondary rise in cases of a clinical relapse. Free elastase and fibronectin/albumin ratio in the bronchial lavage did not correlate to the clinical course. Dexamethasone seems to have not only an effect on fluid balance but also on the alveolar capillary leakage and the PMN influx into the lung. This might explain the superior effect of dexamethasone in patients with Northway stage I/II BPD in comparison to infants with Northway stage III/IV. PMID- 1762999 TI - [Quantitative assessment of partial flow-volume curves in respiratory healthy and sick infants and young children]. AB - In 83 patients of 1 to 24 months of age the flow quotients were calculated at 75, 50 and 25% of the tidal volume. The subjects were classified into four groups, depending on their basic disease: 1. healthy patients in respect of respiration; 2. patients with intrathoracic obstruction; 3. patients with extrathoracic obstruction and 4. patients suffering from a combined obstruction. It was found that in particular the quotient Fi25/Fe25 is suitable for differentiation between the studied groups. PMID- 1763000 TI - [Cold air provocation as a methods of differential diagnosis of bronchial asthma and chronic bronchitis]. AB - To assess the usefulness of cold air hyperventilation challenge for the diagnosis of bronchial asthma (B. a.) and chronic bronchitis (c. B.) we studied 25 children with B. a. and 11 children with c. B. between 7 and 14 years. After baseline pulmonary function studies in a whole-body-plethysmograph and spirometry cold air challenge was done by 3 minutes hyperventilation of dry subfreezing (-15 degrees C) air in stepwise increasing doses of 20, 40 and 60% of maximum breathing capacity (MVV). Target size was specific airways resistance (sRaw). Its increase by 100% was considered a positive reaction. Thoracic gas volume (ITGV), airways resistance (Raw) and forced expiratory volume in one second (FEV1) were measured as well. The moment of maximum airway reaction and the time course of the recovery period were also studied. 18 children with B. a. and 1 patient with c. B. reacted significantly with sRaw. We neither found a reaction plateau nor a consistent moment of maximum reaction. Children with B. a. reacted especially with ITGV. PMID- 1763001 TI - [Bronchial hyperreactivity to physiological saline solution]. AB - A case of a 10-year old boy suffering from asthma bronchiale following pleuropneumonia is reported. Paradoxically, bronchospasmolysis tests using physiological saline + salbutamol or ipratropium bromide impaired the lung function of this patient. Salt solutions inhaled in increasing doses until 1.4% generated severe bronchoconstriction, however, inhalation of DNCG + salbutamol normalized the lung function completely. PMID- 1763002 TI - [Treadmill ergometry with submaximal load in children and adolescents with mucoviscidosis (CF)]. AB - Patients suffering from mucoviscidosis can improve their quality of life and can cope with greater physical load if they undergo intensive treatment. This can be objectively confirmed by measuring the lung function, by performing a blood gas analysis and by means of a self-rating mood scale. Load tests can be performed additionally, e.g. by a treadmill ergometer. Only two of 22 patients attained a level of 1 w/kg, in 21 patients the pulse rate increased partly long before the end of the test to more than 130 beats per minute. The rate at which the test was discontinued, was attained by all the patients. There was a significant volume increase after load. Blood gas pCO2 dropped significantly afterload, whereas pO2 did not change. PMID- 1763003 TI - [A 13-year-old boy with a mild form of cystic fibrosis and heterozygote gene mutation for Delta F508]. AB - We report a 13-year old boy with a chronic pseudomonas bronchitis who was first diagnosed as having cystic fibrosis at this age because of an elevated sweat chloride employing pilocarpine-iontophoresis. He is heterozygote for the gene mutation Delta F508. We point out the often moderate course of illness in compound heterozygotes. PMID- 1763004 TI - [Local immunization against P. aeruginosa with an outer-membrane-protein vaccine]. AB - Averting initial colonization of the respiratory tract with P. aeruginosa would be of great benefit for patients with cystic fibrosis (CF). Our approach to this problem is mucosal immunization with a vaccine prepared from the OMP fraction of a PAO-1 strain of P. aeruginosa. Sprague-Dawley rats were given 5 intragastric doses of the vaccine on 5 consecutive days and an intranasal booster dose 21 days later. Immunized animals developed high titers of OMP-specific IgG antibodies in serum and a specific IgA response in bronchioalveolar and small intestinal lavage samples, all determined by ELISA. When challenged 7 days after the booster (day 28) by intratracheal injection of live bacteria of a heterologous strain of P. aeruginosa the immunized rats showed enhanced bronchopulmonary bacterial clearance compared to nonimmunized controls, as indicated by bacterial counts from homogenized lung tissue taken 4 hrs after challenge. Thus, mucosal immunization with OMP vaccines might hinder initial colonisation of the lungs with P. aeruginosa. PMID- 1763005 TI - [Fibrosing alveolitis in a 7-year-old girl with autoimmune hemolytic anemia and autoimmune hepatitis]. AB - A Coombs-positive haemolytic anaemia with proof of heat autoagglutinins and autoantibodies against cell nuclei was diagnosed in a girl, now 7 1/2 years of age, in the sixth month of her life as a sequel to jaundice. Shortly afterwards liver biopsy yielded a confirmed diagnosis of giant cell hepatitis. The signs of the disease receded under treatment with decortin and imurek. An attempt to discontinue the medication at 5 1/2 years of age resulted in a histologically confirmed recurrence of autoimmune hepatitis. When the patient was 5 years old, the x-ray revealed a mainly interstitial pneumonia; at 6 years of age, bronchiectases in the region of the left lower lobe were confirmed by bronchography. Resection of the lower lobe was performed after occurrence of atelectasis. Histopathological findings confirmed fibrotic alveolitis associated with giant cells. Based on the overall clinical course and the histological and immunological findings, autoimmune etiology of fibrotic alveolitis must be discussed. Progression of the disease could be avoided during the past 6 months by intensifying the immunosuppressive prednisolone therapy. PMID- 1763006 TI - [Plasma cell granuloma of the lung]. AB - Isolated primary tumors of the lung are rarely seen in childhood and are benign in one third of the patients. Plasma cell granulomas represent the most common benign tumor of the lung in this age group. Histologically, the tumor is characterized by the various components of a chronic inflammation or granulation tissue. Frozen sections can pose difficulties in the differentiation between a malignant and benign process. In view of the case history of our patient we set out to demonstrate that a knowledge of the clinical picture and a correct interpretation of associated laboratory findings facilitate diagnosis. To our knowledge we describe for the first time the ultrastructural findings of so called "microtubule-reticular structures" giving further evidence of the inflammatory origin of this lesion. PMID- 1763007 TI - [Juvenile laryngeal papillomatosis--a case report]. AB - Juvenile papillomatosis of the larynx is a disease of viral origin and is a rare cause of hoarseness and stridor in childhood. Although the tumours are basically benign, they may present problems in therapy due to their localisation and marked tendency to recur. According to the present state of knowledge, a combination of laser coagulation and alpha-interferon therapy is the treatment of choice. It can be applied on a long-term basis effectively and with few side effects due to individualised dosage determination. We report on a girl patient of 2 1/2 years of age with recurrent juvenile papillomatosis of the larynx. Long-term alpha interferon therapy was so far successful in preventing progress of the pattern of findings. Treatment is well tolerated after the most suitable dose has been found for a particular patient. No side effects were seen that would have compelled us to discontinue the treatment. We are planning to continue interferon therapy for at least 1 to 2 years with regular endoscopic control. PMID- 1763008 TI - [Congenital chylothorax]. PMID- 1763009 TI - [Radiological diagnosis of congenital malformations of the tracheobronchial tree]. AB - Diagnostic imaging in congenital abnormalities of the tracheo-bronchial tree needs new discussion. Common malformations are referred including diagnostic sequences. PMID- 1763010 TI - [Surgical indications in bronchopulmonary malformations in childhood]. AB - Especially in childhood, the diagnosis of bronchopulmonary malformations should be carried out to such an extent as to enable an appraisal of the probable further development of symptoms. If increasing complications and secondary damage are impending, there should be no hesitation in having surgical treatment carried out by an experienced thorax surgeon even in early childhood, if possible before an absolutely life-threatening situation is present. Without exception, there were no complications in the postoperative courses, and the good development of symptom-free children with normalized lung function document the rational justification for thorax surgery in various bronchopulmonary malformations. PMID- 1763011 TI - [Diagnostic basic program in pneumological services: current conditions--a retrospective analysis. Work Group of administrative hospital physicians of pneumological services]. PMID- 1763012 TI - Chemical implementation of neural networks and Turing machines. AB - We propose a reversible reaction mechanism with a single stationary state in which certain concentrations assume either high or low values dependent on the concentration of a catalyst. The properties of this mechanism are those of a McCulloch-Pitts neuron. We suggest a mechanism of interneuronal connections in which the stationary state of a chemical neuron is determined by the state of other neurons in a homogeneous chemical system and is thus a "hardware" chemical implementation of neural networks. Specific connections are determined for the construction of logic gates: AND, NOR, etc. Neural networks may be constructed in which the flow of time is continuous and computations are achieved by the attainment of a stationary state of the entire chemical reaction system, or in which the flow of time is discretized by an oscillatory reaction. In another article, we will give a chemical implementation of finite state machines and stack memories, with which in principle the construction of a universal Turing machine is possible. PMID- 1763013 TI - Infrared spectroscopy of exfoliated human cervical cells: evidence of extensive structural changes during carcinogenesis. AB - Infrared spectra were obtained from exfoliated cervical cells from 156 females, of whom 136 were normal, 12 had cervical cancer, and 8 had dysplasia. The spectra of the normal women, essentially identical, differed from those obtained from patients with either cancer or dysplasia. In malignant samples we noted (i) significant changes in the intensity of the glycogen bands at 1025 cm-1 and 1047 cm-1, the bands at 1082 cm-1 and 1244 cm-1, the C--O stretching band at 1155 cm 1, and the band at 1303 cm-1, (ii) significant shifts of the peaks normally appearing at 1082 cm-1, 1155 cm-1, and 1244 cm-1, and (iii) an additional band at 970 cm-1. Further study of several of these bands, including the pressure dependence of their frequencies, revealed that in the malignant cervical tissue there were extensive changes in the degree of hydrogen bonding of phosphodiester groups of nucleic acids and C--OH groups of proteins, as well as changes in the degree of disorder of methylene chains of lipids. The IR spectra of samples with dysplasia demonstrated the same changes with cancer samples, except that the changes were of lesser magnitude and the phosphodiester peak normally appearing at 1082 cm-1 did not shift. These spectroscopic changes appear to progress in tandem with the morphological changes that lead normal cervical epithelium to cancer through the premalignant stage of dysplasia. The diagnostic potential of IR spectroscopy is discussed. PMID- 1763014 TI - Demographic predisposition to the evolution of eusociality: a hierarchy of models. AB - I present a hierarchy of models that illustrate, within the framework of inclusive fitness theory, how demographic factors can predispose a species to the evolution of eusociality. Delayed reproductive maturation lowers the inclusive fitness of a solitary foundress relative to that of a worker. Variation in age at reproductive maturity makes the worker strategy more profitable to some individuals than to others and thus predicts the coexistence of single-foundress and multiple-foundress nesting associations. Delayed reproductive maturation and variation in age at reproductive maturity also select for mixed reproductive strategies so that some individuals whose reproductive maturation is expected to be delayed can first act as workers and later switch over to the role of a queen or foundress. Assured fitness returns shows how identical mortality rates can have different consequences for workers and solitary nest foundresses because a solitary foundress will have to necessarily survive for the entire duration of development of her brood, whereas a worker can hope to get proportional fitness returns for short periods of work. In concert with assured fitness returns, delayed reproductive maturation and variation in age at reproductive maturity become more powerful in selecting for worker behavior, and mixed reproductive strategies become available to a wider range of individuals. These phenomena provide a consistently more powerful selective advantage for the worker strategy than do genetic asymmetries created by haplodiploidy. PMID- 1763015 TI - Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. AB - Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2' deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers. PMID- 1763016 TI - Basic fibroblast growth factor released by single, isolated cells stimulates their migration in an autocrine manner. AB - Basic fibroblast growth factor (bFGF), a protein with angiogenic, mitogenic, and chemotactic properties, lacks a signal sequence and is not secreted via the classical secretory pathway. However, the growth factor is known to act extracellularly. Since no defined mechanism for bFGF release has been described, it has been suggested that this growth factor is released from dead or damaged cells. To test this hypothesis we characterized the effect of exogenously added bFGF and neutralizing antibody on the migration of single, isolated NIH 3T3 cells transfected with bFGF cDNA. Under these conditions the observed cell cannot be affected by bFGF derived from other cells. Cells were seeded onto colloidal gold coated coverslips at a density of one cell per coverslip. A cell migrating on this substrate produces a track free of refringent gold particles that is measured by an image analyzer. The results showed that cell motility directly correlated with the amount of bFGF released from the migrating cells. Affinity purified anti-bFGF antibody, but not irrelevant IgG, reduced the level of migration of the bFGF transfectants to that of the control cells transfected with the vector alone, showing that bFGF stimulates migration of the cell that releases it. Thus, bFGF is secreted by viable cells and mediates cell functions via a "true" autocrine mechanism. PMID- 1763017 TI - Identification and characterization of rat intestinal trefoil factor: tissue- and cell-specific member of the trefoil protein family. AB - The trefoil peptide family encompasses a group of small proteins that appear to assume a distinctive secondary structure that leads to intrinsic resistance to protease digestion. Induction of these peptides has been associated with response to injury in the gastrointestinal tract and related organs. Using an oligonucleotide derived from N-terminal amino acid sequencing of a transformed growth-inhibiting protein, a cDNA was cloned from rat intestinal villus epithelial cells that encodes a protein 81 amino acids in length with the characteristic trefoil peptide cysteine residue motif. Northern blot analysis demonstrates specific expression of a single transcript of 0.43 kilobase in small and large intestinal epithelium in rat and man. Indirect immunofluorescent staining with antiserum raised using a synthetic peptide based on the predicted C terminal sequence of this protein, designated intestinal trefoil factor, demonstrated that it is primarily expressed and secreted onto the intestinal surface by goblet cells, suggesting that it may be an important component of intrinsic mechanisms for defending mucosal integrity. PMID- 1763018 TI - Interleukin 2- and interleukin 5-induced changes in the binding of regulatory factors to the J-chain gene promoter. AB - In a primary immune response, B cells require signals from the T-cell lymphokines interleukins 2 and 5 (IL-2 and IL-5) to develop into IgM-secreting cells. One role of IL-2 and IL-5 is to activate transcription of the gene encoding the IgM joining component, the J chain. In this study the activation mechanism was investigated by using an inducible beta-lymphoma cell line to examine J-chain RNA expression and factor binding to the J-chain promoter. The analyses revealed that both IL-2 and IL-5 trigger a decrease in the binding of two promoter-specific nuclear proteins that precedes the appearance of J-chain RNA. In combination the two lymphokines effected nearly additive changes in factor binding and J-chain RNA abundance. Both effects were reversed upon withdrawal of the lymphokine stimulus and both were inhibited in the presence of the T-cell lymphokine IL-4. These findings indicate that the IL-2 and IL-5 signal pathways converge to deliver a common signal that regulates the repressor activities of two lymphokine responsive promoter elements. PMID- 1763019 TI - The structure of the antigen-binding groove of major histocompatibility complex class I molecules determines specific selection of self-peptides. AB - We have examined the effect of diversity in the antigen-binding groove of the Kb, Db, Kbm1, and Kbm8 major histocompatibility complex (MHC) class I molecules on the set of self-peptides they present on the cell surface, by using a procedure we recently developed in our laboratory to isolate endogenously processed peptides bound to MHC class I molecules. We found that such naturally processed peptides are 7-10 amino acids long. A major motif of tyrosine and phenylalanine residues at positions three and five was found for peptides binding to Kb. The availability of Kb mutant molecules Kbm1 and Kbm8, each with localized clustered changes in the antigen-binding cleft, allowed us to probe the effect of such small alterations on peptide selection. We found that such changes in different regions in the antigen-binding groove exert an absolute effect by changing subsets of self-peptides bound to these MHC molecules. In the Kbm1 mutant, the binding of the characteristic major set of Kb-associated peptides with tyrosine at position three or both positions three and five is abrogated, although this MHC molecule still binds peptides with tyrosine at position seven; the latter peptides also bind to Kb. Kbm8 shares the major Tyr-3, Tyr-5 peptide set that binds to Kb but does not bind the peptides with tyrosine at position seven. Thus differences in binding selectivity in Kbm1 and Kbm8 appear to be the major determinant for the observed alterations in in vivo immune responses. PMID- 1763020 TI - Magnetic field tomography of coherent thalamocortical 40-Hz oscillations in humans. AB - This paper introduces the use of magnetic field tomography (MFT), a noninvasive technique based on distributed source analysis of magnetoencephalography data, which makes possible the three-dimensional reconstruction of dynamic brain activity in humans. MFT has a temporal resolution better than 1 msec and a spatial accuracy of 2-5 mm at the cortical level, which deteriorates to 1-3 cm at depths of 6 cm or more. MFT is used here to visualize the origin of a spatiotemporally organized pattern of coherent 40-Hz electrical activity. This coherence, initially observed during auditory input, was proposed to be generated by recurrent corticothalamic oscillation. In support of this hypothesis, we illustrate well-defined 40-Hz coherence between cortical-subcortical sites with a time shift that is consistent with thalamocortical conduction times. Studies on Alzheimer patients indicate that, while a similar activity pattern is present, the cortical component is reduced in these subjects. PMID- 1763021 TI - Sustained activation of protein kinase C is essential to HL-60 cell differentiation to macrophage. AB - Although a single dose of phorbol 12-myristate 13-acetate (PMA) allowed HL-60 cells to differentiate to macrophages, a single dose of membrane-permeant diacylglycerol (DAG), 1,2-dioctanoylglycerol (1,2-DiC8), was normally insufficient to differentiate these cells. These cells metabolized 1,2-DiC8 very rapidly, and 1,2-DiC8 available to protein kinase C (PKC) activation was removed from the incubation medium at a rate proportional to cell density. However, increasing the duration of exposure of HL-60 cells to this DAG either by its repeated addition or by decreasing the cell density greatly enhanced their differentiation to macrophages as measured by CD11b expression. During this differentiation induced by DAG, neither measurable translocation nor depletion (down-regulation) of PKC was observed. When the cells were exposed to PMA, on the other hand, some PKC subspecies were instantaneously translocated to membranes and subsequently disappeared very quickly, whereas the alpha-subspecies was decreased to the level of approximately 60% of the resting cell, but thereafter its activity was maintained at a nearly constant level in membranes. After approximately 4 hr, the PKC subspecies, once depleted, reappeared gradually in the membrane fraction. The results suggest that sustained activation of PKC is essential to differentiation of HL-60 cells to macrophages, and depletion of the enzyme is not needed. Perhaps translocation of PKC represents an extreme state of the active form of the enzyme, which may result from PMA action, and the alpha subspecies presumably plays a key role in HL-60 cell differentiation. PMID- 1763022 TI - Bag model for DNA migration during pulsed-field electrophoresis. AB - A model for pulsed-field electrophoresis was developed by picturing large DNA as a deformable "bag" that (i) moves with limiting mobility in a continuous electric field, (ii) adopts an orientation aligned with the field direction, and (iii) reorients after a change in field direction in a size-dependent manner. The model correctly predicted the resolution of large DNA in a pulsed field including the surprising phenomena of mobility inversion, lateral band spreading, and improved resolution for obtuse angles. A simple parametrization agreed with observations of two completely different aspects of DNA behavior: bulk mobility as measured during gel electrophoresis and molecular reorientation as measured by linear dichroism. The model also provides quantitative guidelines for setting experimental parameters in pulsed-field electrophoresis experiments. PMID- 1763023 TI - A strategy for finding classes of minima on a hypersurface: implications for approaches to the protein folding problem. AB - Locating the native structure of a given protein is a task made difficult by the complexity of the potential energy hypersurface and by the huge number of local minima it contains. We have explored a strategy (the "antlion" method) for hypersurface modification that suppresses all minima but that of the native structure. Transferrable penalty functions with general applicability for modifying a hypersurface to retain the desired minimum are identified, and two blocked oligopeptides (alanine dipeptide and tetrapeptide) are used for specific numerical illustration of the dramatic simplification that ensues. In addition, an intermediary role for neural networks to manage some aspects of the antlion strategy applied to large polypeptides and proteins is introduced. PMID- 1763024 TI - Uncoupling thermotolerance from the induction of heat shock proteins. AB - Exposure of cells to elevated temperatures causes a rapid increase in the synthesis of heat shock proteins (hsps) and induces thermotolerance, the increased ability of cells to survive exposure to lethal temperatures; however, the connection between hsp induction and the acquisition of thermotolerance is unclear. hsp induction in the yeast Saccharomyces cerevisiae is mediated by the activation of heat-shock transcription factor, and recently we have described a mutation, hsf1-m3, in heat-shock transcription factor that prevents the factor's activation. We now demonstrate that this mutation results in a general block in heat-shock induction but does not affect the acquisition of thermotolerance. Our results indicate that high-level induction of the major hsps is not required for cells to acquire thermotolerance. PMID- 1763025 TI - Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression. AB - Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, greater than 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for greater than 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in less than 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P less than 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs. PMID- 1763026 TI - Folding of group I introns from bacteriophage T4 involves internalization of the catalytic core. AB - Fe(II)-EDTA, a solvent-based cleavage reagent that distinguishes between the inside and outside surfaces of a folded RNA molecule, has revealed some of the higher-order folding of the group IB intron from Tetrahymena thermophila pre rRNA. This reagent has now been used to analyze the bacteriophage T4 sunY and td introns, both of which are members of the group IA subclass. Significant portions of the phylogenetically conserved secondary structure are protected from Fe(II) EDTA cleavage. However, the P4 secondary structure element, which is substantially protected in the Tetrahymena intron, is available for cleavage in the two T4 introns. We conclude that a family of catalytic RNAs (ribozymes) that possess similar secondary structures and have similar activities fold into similar but nonidentical tertiary structures that nevertheless serve to internalize portions of the catalytic center. Furthermore, comparison of cleavage patterns of the sunY and td intron RNAs indicates that conserved nucleotides outside as well as within the catalytic core participate in the tertiary structure. PMID- 1763027 TI - The C-terminal region of the Vibrio fischeri LuxR protein contains an inducer independent lux gene activating domain. AB - The Vibrio fischeri luminescence genes are activated by an autoinducer and the 250-amino acid residue LuxR protein. To develop a general view of LuxR structure and function, a set of luxR 5'-deletion mutations was generated. Ten luxR mutant plasmids encoding active LuxR proteins with deletions ranging from residues 2-5 (delta 2-5) to residues 2-182 (delta 2-182) were studied. The degree of transcriptional activation of luminescence genes by the truncated LuxR proteins ranged from 0.01% to greater than 200% of the wild-type level. LuxR proteins with small deletions (up to delta 2-20) were active and remained autoinducer dependent, LuxR proteins with deletions between residues 2-58 and 2-138 showed low activity and were not affected by autoinducer, and LuxR proteins with large deletions such as the delta 2-162 protein were highly active and autoinducer independent. However, proteins with deletions equal to or greater than delta 2-20 were unable to autoregulate luxR. Our data indicate there is a C-terminal LuxR domain capable of functioning as a transcriptional activator. We suggest that an N-terminal region of LuxR starting between residues 20 and 58 and extending to the region of residues 138-162 masks the activator function of the C-terminal domain. Residues prior to position 20 are needed for autoregulatory function. Experiments showing that wild-type luxR is dominant over luxR genes coding the delta 2-58 through delta 2-138 proteins indicate the N-terminal arm masks lux DNA binding. PMID- 1763028 TI - Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries. AB - A number of experiments on the shuffling of heavy and light chains from antibodies of defined specificity for the transition-state analogue hapten nitrophenyl phosphonamidate are described. The experiments report on the promiscuity of heavy and light chains in binding antigen and the feasibility of antibody redesign by this shuffling process. The concepts of incestuous and extraclonal promiscuous association are described. Shuffling opens the possibility of generating panels of antibodies with related specificity but of distinct idiotypic composition that may have significance in the use of human monoclonal antibodies in therapy. PMID- 1763029 TI - Calorie restriction suppresses subgenomic mink cytopathic focus-forming murine leukemia virus transcription and frequency of genomic expression while impairing lymphoma formation. AB - Calorie restriction suppresses mammary proviral mRNA expression and protooncogene activation in breast tumor-prone C3H/Ou mice while inhibiting tumor formation. To determine whether the beneficial effects of chronic energy-intake restriction (CEIR) can be extended to an organ site of retrovirus-induced tumorigenesis where the dynamics of growth and sexual maturity are not paramount as they are in breast tissue, calorie restriction of 40% was imposed on thymic lymphoma-prone AKR mice when 4 weeks old. Recombination between various murine leukemia virus (MuLV) mRNAs, resulting in the generation of an 8.4-kilobase genomic-length transcript with mink cytopathic focus-forming (MCF) characteristics, is considered the proximal retroviral event in AKR lymphomagenesis. Thymic expression of subgenomic MCF MuLV mRNA was uniformly suppressed among 6- and 8 week-old CEIR mice (P less than 0.02). This suppression of MuLV transcription preceded a 25% reduction in the appearance of genomic-length MCF transcripts among CEIR mice and a 28% reduction in cumulative lymphoma mortality. The latency to median tumor incidence was extended greater than 3 months by calorie restriction, and median lifespan was extended approximately 50%. Survival curves for the full-fed and CEIR dietary cohorts were found to be significantly different (P less than 0.0001), with full-fed mice experiencing a 3 times greater risk of lymphoma mortality. These findings extend the known range of pathologic states influenced by CEIR in inbred mice and show that retroviral mechanisms involved in generation of lymphoid malignancy can be significantly impaired by calorie restriction. PMID- 1763030 TI - Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. AB - Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia. PMID- 1763031 TI - Low-resolution genome map of the malaria mosquito Anopheles gambiae. AB - We have microdissected divisions of the Anopheles gambiae polytene chromosomes, digested the DNAs with a restriction enzyme, and PCR-amplified the DNA fragments to generate a set of pooled probes, each corresponding to approximately 2% of the mosquito genome. These divisional probes were shown to have high complexity. Except for those derived from near the centromeres, they hybridize specifically with their chromosomal sites of origin. Thus, they can be used to map cloned DNAs by a dot blot procedure, which is much more convenient than in situ hybridization to polytene chromosomes. We discuss additional potential uses of these probes, such as easier isolation of molecular markers and genes, including those that cross-hybridize with clones available from other insects. It is expected that the probes will substantially accelerate molecular genetic analysis of this most important malaria vector. PMID- 1763033 TI - Mechanism of the initial charge separation in bacterial photosynthetic reaction centers. AB - The initial electron transfer in reaction centers from Rhodobacter sphaeroides R26 was studied by a subpicosecond transient pump-probe technique. The measured kinetics at various wavelengths were analyzed and compared with several mechanisms for electron transfer. An unambiguous determination of the initial electron transfer mechanism in reaction centers cannot be made by studying the anion absorption region (640-690 nm), due to the spectral congestion in this region. However, correlations between the stimulated emission decay of the excited state of the special pair, P*, at 926 nm and bleaching of the bacteriopheophytin Qx absorption at 545 nm suggest that the electron transfer at 283 K is dominated by a two-step sequential mechanism, whereas one-step superexchange and the two-step sequential mechanism have about equal contributions at 22 K. PMID- 1763032 TI - Reconstitution of tracheal grafts with a genetically modified epithelium. AB - A rational approach to the development of gene therapies for cystic fibrosis requires a better understanding of the cellular targets for gene transfer in the airway epithelium. We have used recombinant retroviruses to study the dynamics and lineage relationships of a regenerating rat tracheal epithelium. Primary cultures of tracheal epithelial cells were exposed to lacZ-transducing retroviruses and subsequently seeded into denuded trachea that were implanted into BALB/c (nu/nu) mice. The grafts developed a fully differentiated mucociliary epithelium containing large clones of lacZ-expressing cells with virtually all cell types represented within each clone. These data are most consistent with gene transfer into a putative progenitor cell that is capable of extensive self renewal and pleuripotent development. Vector-specific variation in transgene expression was noted in the various cell types. PMID- 1763034 TI - Rapid-flow resonance Raman spectroscopy of bacterial photosynthetic reaction centers. AB - Rapid-flow resonance Raman vibrational spectra of bacterial photosynthetic reaction centers from the R-26 mutant of Rhodobacter sphaeroides have been obtained by using excitation wavelengths (810-910 nm) resonant with the lowest energy, photochemically active electronic absorption. The technique of shifted excitation Raman difference spectroscopy is used to identify genuine Raman scattering bands in the presence of a large fluorescence background. The comparison of spectra obtained from untreated reaction centers and from reaction centers treated with the oxidant K3Fe(CN)6 demonstrates that resonance enhancement is obtained from the special pair. Relatively strong Raman scattering is observed for special pair vibrations with frequencies of 36, 94, 127, 202, 730, and 898 cm-1; other modes are observed at 71, 337, and 685 cm-1. Qualitative Raman excitation profiles are reported for some of the strong modes, and resonance enhancement is observed to occur throughout the near-IR absorption band of the special pair. These Raman data determine which vibrations are coupled to the optical absorption in the special pair and, thus, probe the nuclear motion that occurs after electronic excitation. Implications for the interpretation of previous hole-burning experiments and for the excited-state dynamics and photochemistry of reaction centers are discussed. PMID- 1763035 TI - The 29-kDa proteins phosphorylated in thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein. AB - Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. We have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, we isolated and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the "estrogen receptor-related protein" is HSP27, and the three major 29-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation. PMID- 1763036 TI - Dose-dependent differences in the profile of mutations induced by an ultimate carcinogen from benzo[a]pyrene. AB - Mutations in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-79 cells were examined after exposure of the cells to a high cytotoxic dose (0.48 microM; 35% survival) and a low noncytotoxic dose (0.04 microM; 100% survival) of the ultimate carcinogen (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BPDE]. Independent 8-azaguanine-resistant colonies were isolated and cDNAs were prepared by reverse transcription. The coding region of the cDNA of the HPRT gene was amplified by the polymerase chain reaction and sequenced. An examination of the DNA base sequence changes induced by different doses of (+)-BPDE demonstrated that the high dose of (+)-BPDE caused base substitution mutations almost exclusively at G.C base pairs whereas the low dose of (+)-BPDE caused mutations at both G.C and A.T base pairs. Thus, use of a low dose of (+)-BPDE allowed the detection of mutations (at A.T base pairs) that were not readily observed with a high dose of (+)-BPDE. The data also suggest that the low dose of (+)-BPDE may have caused a different profile of base substitutions at G.C base pairs and exon deletions than the high dose. The results indicate dose-dependent differences in the profile of mutations for an ultimate carcinogen. PMID- 1763037 TI - Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is a congenital disorder in which phagocytes cannot generate superoxide (O2-) and other microbial oxidants due to mutations in any one of four components of the O2(-)-generating complex, NADPH oxidase. We report here a female CGD patient in whom a missense mutation in one of these components, the p22-phox subunit of the neutrophil membrane cytochrome b [where phox indicates phagocyte oxidase (used to designate protein components of the phagocyte NADPH oxidase)] results in a nonfunctional oxidase and failure of neutrophils to produce O2- in response to phorbol 12-myristrate 13-acetate. Cytochrome b in the patient's neutrophils was normal in appearance and abundance as determined by visible spectroscopy and by immunoblots of the gp91 and p22 subunits. However, the neutrophil plasma membranes were devoid of activity in the cell-free oxidase activation system, whereas the cytosol functioned normally. We postulated that the patient was homozygous for a mutation in p22 that results in the synthesis of normal levels of a nonfunctional cytochrome b. A single-base substitution (C----A) was found in the patient's mononuclear cell p22-phox cDNA that predicts a nonconservative Pro----Gln substitution at residue 156. The same mutation was also identified in all clones sequenced from patient genomic DNA, demonstrating homozygosity for the mutant allele. An antipeptide antibody against p22 residues 153-164 was found to bind only to permeabilized neutrophils, indicating that the mutation occurs in a cytoplasmic domain. These studies establish that this domain of p22-phox is cytoplasmic and that mutations in this region can have profound effects on cytochrome b function. PMID- 1763038 TI - Evolution of human immunodeficiency virus type 1 nucleotide sequence diversity among close contacts. AB - The degree of change in the nucleotide sequence of human immunodeficiency virus type 1 (HIV-1) that occurs when it is transmitted sexually from one individual to another or vertically from mother to child is unknown. Previous studies have shown that most cultured HIV-1 isolates from the same individuals differed in the entire envelope gene nucleotide sequence by up to 2%, although most isolates from unrelated individuals differed by 6-22%. To examine diversity among HIV-1 isolates from close contacts, we determined the nucleotide sequences of viruses from a family with a known epidemiologic profile, in which a woman transmitted HIV-1 heterosexually to her partner and vertically to her daughter. Direct DNA sequence analysis of primary HIV-1 isolates amplified by PCR was used to distinguish the major and minor viral sequences, termed quasispecies, to rapidly determine the predominant sequences and their phylogenetic relationships. The nucleotide sequence diversity of a major portion of the HIV-1 envelope gene was 3.7% between isolates from the woman and her heterosexual partner and 8.5% between isolates from this woman and her daughter, who had been infected for a longer period than the partner. The configuration of the phylogenetic tree demonstrated that the daughter's predominant isolate evolved from a progenitor of her mother's current strain. This study provides evidence of a continuous spectrum of sequence diversity between any two isolates ranging from those derived from the same person to those from close contacts and, ultimately, those from unrelated individuals. These data and methods can be applied to epidemiologic investigations of possible HIV-1 transmission between health care workers and their patients. PMID- 1763039 TI - A damage-responsive DNA binding protein regulates transcription of the yeast DNA repair gene PHR1. AB - The PHR1 gene of Saccharomyces cerevisiae encodes the DNA repair enzyme photolyase. Transcription of PHR1 increases in response to treatment of cells with 254-nm radiation and chemical agents that damage DNA. We report here the identification of a damage-responsive DNA binding protein, termed photolyase regulatory protein (PRP), and its cognate binding site, termed the PHR1 upstream repression sequence, that together regulate induction of PHR1 transcription after DNA damage. PRP activity, monitored by electrophoretic-mobility-shift assay, was detected in cells during normal growth but disappeared within 30 min after irradiation. Copper-phenanthroline footprinting of PRP-DNA complexes revealed that PRP protects a 39-base-pair region of PHR1 5' flanking sequence beginning 40 base pairs upstream from the coding sequence. A prominent feature of the foot printed region is a 22-base-pair palindrome. Deletion of the PHR1 upstream repression sequence increased the basal level expression of PHR1 in vivo and decreased induction after exposure of cells to UV radiation or methyl methanesulfonate, whereas insertion of the PRP binding site between the CYC1 upstream activation sequence and "TATA" sequence reduced basal level expression and conferred damage responsiveness upon a reporter gene. Thus these observations establish that PRP is a damage-responsive repressor of PHR1 transcription. PMID- 1763040 TI - Sex chromosome evolution: platypus gene mapping suggests that part of the human X chromosome was originally autosomal. AB - To investigate the evolution of the mammalian sex chromosomes, we have compared the gene content of the X chromosomes in the mammalian groups most distantly related to man (marsupials and monotremes). Previous work established that genes on the long arm of the human X chromosome are conserved on the X chromosomes in all mammals, revealing that this region was part of an ancient mammalian X chromosome. However, we now report that several genes located on the short arm of the human X chromosome are absent from the platypus X chromosome, as well as from the marsupial X chromosome. Because monotremes and marsupials diverged independently from eutherian mammals, this finding implies that the whole human X short arm region is a relatively recent addition to the X chromosome in eutherian mammals. PMID- 1763041 TI - Locating protein-coding regions in human DNA sequences by a multiple sensor neural network approach. AB - Genes in higher eukaryotes may span tens or hundreds of kilobases with the protein-coding regions accounting for only a few percent of the total sequence. Identifying genes within large regions of uncharacterized DNA is a difficult undertaking and is currently the focus of many research efforts. We describe a reliable computational approach for locating protein-coding portions of genes in anonymous DNA sequence. Using a concept suggested by robotic environmental sensing, our method combines a set of sensor algorithms and a neural network to localize the coding regions. Several algorithms that report local characteristics of the DNA sequence, and therefore act as sensors, are also described. In its current configuration the "coding recognition module" identifies 90% of coding exons of length 100 bases or greater with less than one false positive coding exon indicated per five coding exons indicated. This is a significantly lower false positive rate than any method of which we are aware. This module demonstrates a method with general applicability to sequence-pattern recognition problems and is available for current research efforts. PMID- 1763042 TI - Domain exchange: characterization of a chimeric lipase of hepatic lipase and lipoprotein lipase. AB - Hepatic lipase and lipoprotein lipase hydrolyze fatty acids from triacylglycerols and are critical in the metabolism of circulating lipoproteins. The two lipases are similar in size and amino acid sequence but are distinguished by functional differences in substrate preference and cofactor requirement. Presumably, these distinctions result from structural differences in functional domains. To begin localization of these domains, a chimeric lipase was constructed composed of the N-terminal 329 residues of rat hepatic lipase linked to the C-terminal 136 residues of human lipoprotein lipase. The chimera hydrolyzed both monodisperse short-chain (esterase) and emulsified long-chain (lipase) triacylglycerol substrates with catalytic and kinetic properties closely resembling those of native hepatic lipase. However, monoclonal antibodies to lipoprotein lipase inhibited the lipase activity, but not the esterase function, of the chimera. Therefore, the chimeric molecule is a functional lipase and contains elements and characteristics from both parental enzymes. It is proposed that the N-terminal domain, containing the active center from hepatic lipase, governs the catalytic character of the chimera, and the C-terminal domain is essential for hydrolysis of long-chain substrates. PMID- 1763043 TI - Methylation changes in the apolipoprotein AI gene during embryonic development of the mouse. AB - We report here a detailed study of developmental changes in the methylation status of specific sites in a single-copy tissue-specific gene, from the germ cell through the early embryo to adult tissues. Two sites at the 5' end of the mouse apolipoprotein AI gene were unmethylated in the ovulated unfertilized oocytes and methylated in the sperm. In contrast, a third site, located upstream of the gene, was methylated and a CpG island within the gene was unmethylated in both oocyte and sperm. The methylated sites, regardless of maternal or paternal origin, underwent demethylation in the early embryo (8-16 cells) and stayed unmethylated through the late blastocyst stage. During gastrulation, non-CpG island sites underwent methylation, followed by gradual demethylation at specific sites in tissues parallel to expression of the gene (liver and intestine). The formation of the mature tissue-specific methylation pattern of the apolipoprotein AI gene, therefore, involves the following three major events: (i) erasure of the germ-cell methylation pattern (at the 8- to 16-cell stage), (ii) formation of a new methylation pattern by de novo methylation of non-CpG island sites (during gastrulation), and (iii) tissue-specific demethylation associated with the onset of expression of the gene. PMID- 1763044 TI - CD4-binding regions of human immunodeficiency virus envelope glycoprotein gp120 defined by proteolytic digestion. AB - The gp120 envelope glycoprotein of human immunodeficiency virus type 1 binds the cell surface protein CD4 with high affinity. Here we report the use of proteolysis to define regions of gp120 involved in CD4 binding. Cleavage of gp120 with Staphylococcus aureus V8 protease at residue 269 or with trypsin at residue 432 destroys CD4 binding. These same sites are protected from proteolytic cleavage by bound CD4. Cleavages at 64, 144, 166, 172, and 315 do not affect binding and are not protected by bound CD4, indicating that these regions are not critical for binding CD4. All proteolytic fragments found in coprecipitates with CD4 were covalently associated via disulfides and comprised complete gp120 molecules. Previous conclusions by Nygren et al. [Nygren, A., Bergman, T., Matthews, T., Jornvall, H. & Wigzell, H. (1988) Proc. Natl. Acad. Sci. USA 85, 6543-6546] that both large and small (95-kDa and 25-kDa) V8 proteolytic fragments bind CD4, independently, are not distinguished by their experiments from the result found here that the small fragment immunoprecipitates with CD4 while disulfide-linked to the larger fragment. PMID- 1763045 TI - Positioning of a peptide in the cleft of HLA-A2 by complementing amino acid changes. AB - Several mutant HLA-A2 molecules have been constructed and expressed in the mutant human B-cell line C1R, which lacks HLA-A and HLA-B antigens, and examined for presentation of a previously defined peptide epitope derived from the influenza matrix protein to appropriate human cytotoxic T-lymphocyte lines. When leucine residue 66 in this matrix peptide containing residues 57-68 (matrix peptide 57 68) was replaced by arginine, the resulting matrix peptide 57-68 R66 was not presented to HLA-A2, but the mutation Y116D (tyrosine to aspartic acid at residue 116) in the floor of the peptide binding cleft near its right end dramatically restored peptide presentation. A similar result was obtained by substitution of ornithine for leucine at residue 66. These data provide strong support for a model in which the peptide is orientated with its amino terminus at the left end of the cleft of HLA-A2 and its carboxyl terminus at the right. PMID- 1763046 TI - Ectopic dendrites occur only on cortical pyramidal cells containing elevated GM2 ganglioside in alpha-mannosidosis. AB - In a variety of neuronal storage diseases, cortical pyramidal cells elaborate ectopic dendrites at the axon hillock. A feature common to all the diseases characterized by ectopic dendrites is an elevated level of GM2 ganglioside in cerebral cortex. In cats with one such disease, alpha-mannosidosis, the number of pyramidal cells bearing ectopic dendrites is small; the present study shows that GM2 ganglioside is stored only in those pyramidal neurons exhibiting ectopic dendrites. Using a Golgi-electron microscopy method with periodic acid-Schiff (PAS) staining, we first established that pyramidal cells bearing ectopic dendrites contained PAS+ membranous inclusions, consistent with storage of glycolipids. In contrast, those with smooth axon hillocks accumulated PAS- floccular inclusions, consistent with storage of oligosaccharides. Next, application of a monoclonal antibody against GM2 ganglioside revealed that subsets of both pyramidal and intrinsic neurons contained GM2-like immunoreactivity. Every GM2+ cell contained PAS+ membranous inclusions, indicating that pyramidal cells bearing ectopic dendrites stored GM2 ganglioside. In cats with alpha-mannosidosis induced by swainsonine, some pyramidal neurons showed GM2-like immunoreactivity after 4 weeks of treatment, whereas ectopic dendrites only became evident after 7 weeks of treatment. Thus, GM2 ganglioside accumulated in pyramidal neurons before ectopic dendrites emerged from the axon hillock. We propose that the reinitiation of dendrite growth on mature pyramidal cells is brought about by accumulated GM2 ganglioside. PMID- 1763047 TI - Blast crisis in a murine model of chronic myelogenous leukemia. AB - The P210bcr/abl protein is produced in cells from patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Retroviral transfer of the gene encoding P210bcr/abl into murine bone marrow induces a granulocytic leukemia that models the chronic phase of human CML. We have transferred the leukemic clone to syngeneic animals, albeit with surprising inefficiency, and have observed CML and clonally related acute leukemias of lymphoid or myeloid phenotype in some transplant recipients. These data show that murine CML can result from retroviral transfer of the bcr/abl gene into pluripotent hematopoietic stem cells, that infected clones repopulate poorly after adoptive transfer, and that these clones can give rise to acute leukemia, reflecting evolution to a phase resembling blast crisis in the human disease. PMID- 1763048 TI - Song-selective auditory circuits in the vocal control system of the zebra finch. AB - Birdsong is a learned behavior controlled by a distinct set of brain nuclei. The song nuclei known as area X, the medial nucleus of the dorsolateral thalamus (DLM), and the lateral magnocellular nucleus of the anterior neostriatum (L-MAN) form a pathway that plays an important but unknown role in song learning. One function served by this circuit might be auditory feedback, which is critical to normal song development. We used single unit recordings to demonstrate that all three of these nuclei contain auditory neurons in adult male zebra finches (Taeniopygia guttata). These neurons are song selective: they respond more robustly to the bird's own song than to songs of conspecific individuals, and they are sensitive to the temporal structure of song. Auditory neurons so highly specialized for song within a pathway required for song learning may play a role in the auditory feedback essential in song development. Recordings in the robust nucleus of the archistriatum (RA), the nucleus to which L-MAN projects, showed that RA also contains highly song-selective neurons. RA receives a direct projection from the caudal nucleus of the ventral hyperstriatum (HVc) as well as from L-MAN. We investigated the contributions of these two inputs to auditory responses of RA neurons by selectively inactivating one or both inputs. Our results suggest that there is a song-selective pathway directly from HVc to RA in addition to the circuit via L-MAN. Thus the songbird brain contains multiple auditory pathways specialized for song, and these circuits may vary in their functional importance at different stages of learning. PMID- 1763049 TI - Cloning and expression of a cDNA encoding the alpha subunit of rat p21ras protein farnesyltransferase. AB - The complete amino acid sequence of the alpha subunit of heterodimeric p21ras protein farnesyltransferase from rat has been deduced from the sequence of a cloned cDNA. The cDNA encodes a 377-amino acid protein that migrates on NaDodSO4/polyacrylamide gels identically to the alpha subunit purified from rat brain. When introduced into mammalian cells by transfection, the cDNA for the alpha subunit produced no immunodetectable protein or farnesyltransferase activity unless the cells were simultaneously transfected with a cDNA encoding beta subunit. In light of previous evidence that alpha subunit forms a heterodimer with at least two different beta subunits, current data suggest a mechanism for coordinating amounts of alpha and beta subunits. If an alpha subunit were stable only as a complex with a beta subunit, the number of alpha subunits would be automatically maintained at a level just sufficient to balance all beta subunits, thereby avoiding the potentially toxic overaccumulation of free alpha subunits. PMID- 1763050 TI - RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins. AB - In the yeast Saccharomyces cerevisiae, mutations in either of two unlinked genes, RAM1 or RAM2, abolish the farnesyltransferase activity responsible for prenylation of Ras proteins and the a-factor mating pheromone. Here we report that the function of RAM1 and RAM2 genes is required for the membrane localization of Ras proteins and a-factor. The RAM2 gene was sequenced and can encode a 38-kDa protein. We examined the functional interaction of RAM2 and RAM1 by expressing the genes in Escherichia coli. Extracts derived from an E. coli strain that coexpressed RAM1 and RAM2 efficiently farnesylated a-factor peptide and Ras protein substrates. In contrast, extracts derived from E. coli strains that expressed either RAM gene alone were devoid of activity; however, when the latter extracts were mixed, protein farnesyltransferase activity was reconstituted. These results indicate that the yeast farnesyl-protein transferase is comprised of Ram1 and Ram2 polypeptides. Although Ram1 is a component of the enzyme, disruption of the RAM1 gene in yeast was not lethal, indicating that the Ram1-Ram2 farnesyltransferase is not essential for viability. In contrast, disruption of RAM2 was lethal, suggesting that Ram2 has an essential function in addition to its role with Ram1 in protein farnesylation. PMID- 1763051 TI - Mutants of Escherichia coli initiator tRNA that suppress amber codons in Saccharomyces cerevisiae and are aminoacylated with tyrosine by yeast extracts. AB - We recently described mutants of Escherichia coli initiator tRNA that suppress amber termination codons (UAG) in E. coli. These mutants have changes in the anticodon sequence (CAU----CUA) that allow them to read the amber codon and changes in the acceptor stem that allow them to bind to the ribosomal aminoacyl (A) site. We show here that a subset of these mutants suppress amber codons in Saccharomyces cerevisiae and that they are aminoacylated with tyrosine by yeast extracts. Analysis of a number of mutants as substrates for yeast tyrosyl-tRNA synthetase has led to identification of the C1.G72 base pair and the discriminator base A73, conserved in all eukaryotic cytoplasmic and archaebacterial tyrosine tRNAs, as being important for recognition. Our results suggest that the C1.G72 base pair and the discriminator base, in addition to the anticodon nucleotides previously identified [Bare, L.A. & Uhlenbeck, O.C. (1986) Biochemistry 25, 5825-5830] as important in yeast tyrosyl-tRNA synthetase recognition, may comprise the critical identity determinants in yeast tyrosine tRNA. PMID- 1763052 TI - Premature termination of transcription from the P1 promoter of the mouse c-myc gene. AB - Modulation of transcriptional elongation within the c-myc gene is thought to play a major role in determining levels of c-myc mRNA in both normal and tumor cells. A discrete site of blockage to transcriptional elongation has previously been localized at the 3' end of exon 1 of the mouse and human c-myc genes. We here identify an additional site of transcriptional attenuation that is located between the P1 and P2 promoters of the c-myc gene and that mediates premature termination of transcripts initiating from the P1 promoter. A 95-nucleotide DNA fragment derived from this region prematurely terminated transcription when placed downstream from the promoter of the H-2Kbm1 gene and assayed by expression in Xenopus oocytes. We also show that the previously identified attenuation signal in exon 1 of the mouse c-myc gene can mediate premature termination of P1 initiated transcripts. Premature termination of P1-initiated transcripts presumably increases transcription from the downstream P2 promoter; aberrant regulation of this termination may explain the increased use of the P1 promoter that is characteristic of certain tumors in which myc is overexpressed. PMID- 1763053 TI - Association of ubiquitin-activating enzyme with HeLa cell chromosomes during mitosis. AB - Ubiquitin-activating enzyme (E1) is the first enzyme in the pathway leading to formation of ubiquitin-protein conjugates. Antibodies raised against E1 were affinity purified and used for immunostaining HeLa cells. Condensed chromosomes in mitotic cells were found to be strongly immunoreactive. Chromosomes from metaphase-arrested HeLa cells were isolated and chromosome-associated proteins were analyzed by Western blotting. E1 was detected in fractions containing isolated chromosomes. These results suggest that E1 is associated with condensed chromosomes during mitosis. PMID- 1763054 TI - Terminal region recognition factor 1, a DNA-binding protein recognizing the inverted terminal repeats of the pGKl linear DNA plasmids. AB - The yeast linear DNA plasmids pGKl1 and pGKl2 contain inverted terminal repeats (ITRs) and terminal proteins covalently bound to the 5' termini of each plasmid. The presence of these features suggests a protein-primed mechanism of DNA replication, similar to that exemplified by mammalian adenovirus and phi 29 phage of Bacillus subtilis. In this paper, we report the identification of an activity in cytoplasmic extracts of yeast harboring the pGKl plasmids that recognizes the termini of both pGKl1 and pGKl2. We call this activity TRF1, for terminal region recognition factor 1. Deletion analyses and DNase I protection experiments demonstrate that the activity recognizes base pairs 107-183 within the ITR of pGKl1, and base pairs 126-179 within the ITR of pGKl2. The presence of T-tracts within these two regions, but otherwise dissimilar nucleotide sequences, suggests that TRF1 recognizes a common structural feature within the ITRs of the two plasmids. TRF1 has been partially purified from yeast cytoplasmic extracts and Southwestern analysis indicates that the apparent molecular mass of the protein is 16 kDa. By expressing three open reading frames from pGKl2 in Escherichia coli, we found that open reading frame 10 (ORF10) of pGKl2 encodes TRF1. The sequence of the ORF10 gene product indicates that TRF1 is a highly basic protein of small molecular mass. Comparison of TRF1 with other DNA-binding proteins known to recognize the terminal regions of linear DNAs, such as NFI and NFIII involved in adenovirus DNA replication, and phi 29 p6, involved in phi 29 DNA replication, indicates that TRF1 has a different mode of binding. PMID- 1763055 TI - A test of Fisher's theory of dominance. AB - One of the first patterns noticed by geneticists was that mutations are almost always recessive to their wild-type alleles. Several explanations of this striking pattern have been offered. The two most influential are Fisher's theory- which argues that dominance results from natural selection against recurring deleterious mutations--and Wright's theory--which argues that dominance results from the physiology of gene action. The debate over which of these theories is correct represents one of the most protracted controversies in the history of evolutionary biology. Here I test Fisher's theory by assessing the dominance of mutations in an organism that is typically haploid, the alga Chlamydomonas reinhardtii. The results show that mutations are recessive just as often among haploid as among diploid species. This result falsifies Fisher's theory of dominance and provides strong support for the alternative physiological theory. PMID- 1763056 TI - TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia. AB - Tumor-specific alteration of the TAL1 gene occurs in almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL). We now report the identification of TAL2, a distinct gene that was isolated on the basis of its sequence homology with TAL1. The TAL2 gene is located 33 kilobase pairs from the chromosome 9 breakpoint of t(7;9)(q34;q32), a recurring translocation specifically associated with T-ALL. As a consequence of t(7;9)(q34;q32), TAL2 is juxtaposed with sequences from the T-cell receptor beta-chain gene on chromosome 7. TAL2 sequences are actively transcribed in SUP-T3, a T-ALL cell line that harbors the t(7;9)(q34;q32). The TAL2 gene product includes a helix-loop-helix protein dimerization and DNA binding domain that is especially homologous to those encoded by the TAL1 and LYL1 protooncogenes. Hence, TAL2, TAL1, and LYL1 constitute a discrete subgroup of helix-loop-helix proteins, each of which can potentially contribute to the development of T-ALL. PMID- 1763057 TI - Neural networks as a tool for utilizing laboratory information: comparison with linear discriminant analysis and with classification and regression trees. AB - Successful applications of neural network architecture have been described in various fields of science and technology. We have applied one such technique, error back-propagation, to a medical classification problem stemming from clinical chemistry, and we have compared the performance of two different neural networks with results obtained by conventional linear discriminant analysis or by the technique of classification and regression trees. The results obtained by the various models were tested for robustness by jackknife validation ("leave n out" method). Compared with the two other techniques, neural networks show a unique ability to detect features hidden in the input data which are not explicitly formulated as input. Thus, neural network techniques appear promising in the field of clinical chemistry, and their application, particularly in situations with complex data structures, should be investigated with more emphasis. PMID- 1763058 TI - Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development. AB - Angiotensin II (AII) receptor subtypes were analyzed in the brains of adult and 2 week-old rats by in vitro autoradiography with 125I-labeled [Sar1,Ile8]AII and competition studies with three AII antagonists: the nonpeptide antagonist, DuP 753, which is specific for AT1 receptors that mediate the calcium-inositol phospholipid signaling actions of AII; and nonpeptide (PD 123177) and peptide (CGP 42112A) antagonists that are selective for AT2 receptors of yet unknown function. In the adult rat brain, DuP 753 inhibited radioligand binding to the circumventricular organs and paraventricular nucleus but not to the lateral septum, subthalamic nucleus, and inferior olive. However, binding of 125I-labeled [Sar1,Ile8]AII in the latter regions was inhibited by the AT2 receptor antagonists PD 123177 and CGP 42112A. These areas showed similar displacement by the AT2 receptor subtype-specific antagonists in 2-week-old rats. In addition, radioligand binding at multiple sites of transient expression of AII receptors in 2-week-old rats, including several thalamic nuclei, the nuclei of the 3rd and 12th cranial nerves, geniculate bodies, cerebellum, and cingulate cortex, was displaced by the AT2 antagonists but not by DuP 753. These studies have demonstrated the presence of two AII receptor subtypes in the brain, one (AT1) in areas related to regulation of blood pressure, water intake, and pituitary hormone secretion, and one (AT2) whose function is not yet defined. The abundance and location of brain AT2 receptors in young animals, and the age-related changes in relative expression of the receptor subtypes, suggest that AII exerts specific actions according to the developmental stage of the central nervous system. PMID- 1763059 TI - Interaction of the human T-cell lymphotrophic virus type I (HTLV-I) transcriptional activator Tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-I enhancer. AB - The human T-cell lymphotrophic virus type I (HTLV-I) Tax protein activates transcription from three 21-base-pair (bp) repeat sequences in the viral enhancer. Using gel electrophoretic mobility-shift assays, we now show that Tax interacts directly with the nuclear proteins, Tax activation factors (TAFs), that bind the 21-bp repeats. This interaction is demonstrated by decreased electrophoretic mobilities of the TAFs-21-bp-repeats complexes upon supply of Tax exogenously. Formation of the TAFs-21-bp-repeats and Tax-TAFs-21-bp-repeats complexes correlates with in vivo transactivation by Tax. Furthermore, interaction of Tax with TAFs enhances their binding to the 21-bp repeats. These data indicate that trans-activation by Tax is most likely mediated by interaction of Tax with TAFs. PMID- 1763060 TI - Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. AB - The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules. PMID- 1763061 TI - Intracellular replication is essential for the virulence of Salmonella typhimurium. AB - Salmonella typhimurium is a facultative intracellular parasite, capable of penetrating, surviving, and multiplying within diverse eukaryotic cell types, including epithelial and phagocytic cells. We have been studying intracellular replication of S. typhimurium and found that it is essential in the pathogenesis of this bacterium. A total of 45,000 independent mini-Mu MudJ transposon mutants in S. typhimurium SL1344 were screened in Madin-Darby canine kidney (MDCK) epithelial cells with a beta-lactam, cefotaxime, to enrich for mutants defective for intracellular replication. Ten different auxotrophic (purine, pyrimidine, purine/methionine, and valine/isoleucine) and three prototrophic replication defective mutants (Rep-) were identified. All Rep- mutants showed no differences in aerobic and anaerobic growth patterns, motility, serum sensitivity, mouse macrophage survival, iron uptake, and phosphate requirements. All Rep- mutants were unable to multiply inside MDCK, HeLa, and Caco-2 epithelial cells. When required nutrients for various auxotrophs were supplemented, auxotrophs then replicated inside MDCK cells. Although the parental strain multiplies in large vacuoles inside MDCK cells that distort the host cells, MDCK cells infected with the Rep- mutants appeared relatively normal and few bacteria were seen inside vacuoles. The purine auxotrophs and the three prototrophic Rep- mutants were highly attenuated in mice, and oral and intraperitoneal LD50 levels were 3 to 4 orders of magnitude higher than the wild type level. The three prototrophs were invasive and persisted in the murine organs such as livers and spleens for at least 3 weeks. Therefore, these prototrophic genes are needed for intracellular replication and are essential to the virulence of S. typhimurium. PMID- 1763062 TI - Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys. AB - In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans. PMID- 1763063 TI - The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element. AB - The cell-cell adhesion molecule E-cadherin is specifically expressed in epithelia and is involved in the maintenance of the epithelial phenotype. Expression of E cadherin is downregulated in many poorly differentiated carcinomas, which leads to higher motility and invasiveness of the cells. To examine the mechanisms that regulate tissue-specific expression, we have characterized the promoter of the E cadherin gene. We found that an upstream fragment (positions -178 to +92) mediates strong expression of a chloramphenicol acetyltransferase reporter gene in epithelial cells (i.e., 60% of the level obtained with simian virus 40 promoter/enhancer constructs), whereas in nonepithelial cells this promoter was either inactive or much less active. By DNase I footprinting and gel retardation analysis as well as through functional dissection of the regulatory sequences, we identified two regions that contribute to tissue-specific activity of the promoter: (i) a G-C-rich region between -25 and -58 that generates basic epithelial promoter activity, most likely in combination with an "initiator" element present at the single transcription start site of the gene, and (ii) a palindromic sequence between -75 and -86 (named E-pal) that potentiates the activity of the proximal E-cadherin promoter and confers epithelial cell-specific activity on a simian virus 40 promoter. The E-pal sequence is homologous to cis regulatory elements active in keratin gene promoters and competes with these elements for nuclear factor binding. Interestingly, the activity of the E cadherin promoter was reduced in dedifferentiated breast carcinoma cells, indicating that the identified elements are subject to negative regulation during tumor progression. PMID- 1763064 TI - Phosphorylation state of the GLUT4 isoform of the glucose transporter in subfractions of the rat adipose cell: effects of insulin, adenosine, and isoproterenol. AB - The acute effects of insulin, adenosine, and isoproterenol on the activity, subcellular distribution, and phosphorylation state of the GLUT4 glucose transporter isoform were investigated in rat adipocytes under conditions carefully controlled to monitor changes in cAMP-dependent protein kinase (A kinase) activity. In contrast to GLUT1, which has not been shown to be phosphorylated even when cells are exposed to any of the above agents, GLUT4 was partially phosphorylated (0.1-0.2 mol/mol) when the activity of the A-kinase was suppressed, and remained unchanged in response to insulin. Isoproterenol elicited a 64% inhibition of insulin-stimulated glucose transport activity in the absence, but not the presence, of adenosine receptor agonists. However, in either the presence or the absence of agonists, A-kinase was activated as assessed by examining the phosphorylation of the major adipocyte A-kinase substrate, perilipin. Similarly, under either condition, phosphorylation of GLUT4 was enhanced 1.4-fold in the intracellular membranes, but no significant change was observed in the plasma membrane. In the absence of adenosine receptor agonists, isoproterenol exerted a small (14%) but significant inhibition of the insulin induced translocation of GLUT4 but had no effect on the translocation of GLUT1. Thus, changes in the phosphorylation state and/or subcellular distribution of GLUT4 cannot account for the inhibition of insulin-stimulated glucose activity induced by isoproterenol. PMID- 1763065 TI - Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase. AB - An interferon gamma (IFN-gamma)-inducible protein, gamma 2, was identified by two dimensional gel electrophoresis of transformed human amnion (AMA) cell proteins. cDNA clones coding for this protein have been isolated and characterized as encoding a polypeptide with a predicted molecular weight of 53,165 and a pI of 6.16. Both values are in good agreement with those observed in two-dimensional gel electrophoresis. The gamma 2 protein is found to be highly induced by IFN gamma, whereas no induction was seen after addition of IFN-alpha to AMA cells. A gamma 2-specific 2.7-kilobase mRNA was likewise seen to accumulate selectively in response to IFN-gamma in these cells. Comparison of the predicted amino acid sequence of gamma 2 to proteins in GenBank data bases revealed that gamma 2 is highly homologous to rabbit peptide chain release factor [Lee, C. C., Craigen, W. J., Muzny, D. M., Harlow, E. & Caskey, C. T. (1990) Proc. Natl. Acad. Sci. USA 87, 3508-3512] and bovine tryptophanyl-tRNA synthetase [M. Garret, V. Trezeguet, B. Pajot, J. C. Gandar, M. Merle, M. Guegiev, J. P. Benedetto, C. Sarger, J. Alteriot, J. La Bouessec, J. Labouesse, and J. Bonnet (1990), GenBank accession no. X52113]. Amino acid sequence similarities of 94% and 97%, respectively, are found, which in general would indicate that gamma 2 represents the human equivalent to either of these two mammalian genes. Based on these sequence similarities, the current data raise the possibility that tryptophanyl-tRNA charging and peptide chain release are carried out by the same enzyme. The gamma 2 protein is shown to possess tryptophan-dependent aminoacyl-tRNA synthetase activity and thus constitutes an enzymatic activity involved in the biological activity of IFN-gamma. PMID- 1763066 TI - Amantadine selection of a mutant influenza virus containing an acid-stable hemagglutinin glycoprotein: evidence for virus-specific regulation of the pH of glycoprotein transport vesicles. AB - Mutants of influenza Rostock virus (H7N1 subtype) were selected for resistance to amantadine hydrochloride at concentrations of the antiviral drug known to affect the function of the virus M2 transmembrane protein. Sequence analysis revealed that three mutants had no changes in M2 but contained a lysine to isoleucine substitution in the hemagglutinin (HA) membrane glycoprotein at position 58 of HA2. The mutant viruses were found to fuse membranes at a pH value 0.7 lower than wild type and to exhibit changes in the conformation of their HAs specifically at the lower pH. The homologous lysine to isoleucine substitution was introduced by site-specific mutagenesis into the HA of X-31 influenza virus (H3 subtype), which was expressed by using vaccinia virus recombinants. The expressed HA also mediated membrane fusion and changed in conformation at a pH value 0.7 lower than wild type. These results indicate that increased acid stability of the HA obviates the consequences of the inhibition of M2 function by amantadine and provide further evidence for the role of M2 in regulating the pH of vesicles involved in glycoprotein transport to the cell surface. PMID- 1763067 TI - Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. AB - Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported. PMID- 1763068 TI - Genes for two calcium-dependent cell adhesion molecules have similar structures and are arranged in tandem in the chicken genome. AB - Genomic sequences immediately upstream of the translational start site for the chicken liver cell adhesion molecule (L-CAM) gene contain a second closely related gene, which, because of its location, we have designated the K-CAM gene. Less than 700 base pairs separate the presumed poly(A) site in the K-CAM gene from the translation initiation site for L-CAM. The sizes of exons 4-15 of the K CAM gene are almost identical to those in the L-CAM gene and the exon/intron junctions occur at exactly equivalent positions in both genes. Exon 16, which includes the 3' untranslated region, is much shorter in the K-CAM gene and intron sizes and sequences are not generally conserved between the two genes. Probes from the K-CAM gene hybridized to a 3-kilobase mRNA that was present at high levels in embryonic skin, at lower levels in kidney, heart, and gizzard, and at still lower levels in brain and liver, as determined by Northern blotting. The sequence of the predicted gene product was nearly identical to that of the chicken B-cadherin cDNA, although the distribution of the K-CAM gene transcript differed from that reported for the cadherin. The proximity and identical overall structure of the K-CAM and L-CAM genes strongly suggest that they arose by gene duplication and raise the possibility that genes for other calcium-dependent CAMs may be located in clusters. Moreover, the tandem arrangement of the genes may have important implications for the regulation of their expression. PMID- 1763069 TI - Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. AB - Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechanisms by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminoguanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagent-positive deposits also occurred. Aminoguanidine treatment completely prevented abnormal endothelial cell proliferation and significantly diminished pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder. PMID- 1763070 TI - High-resolution optical imaging of functional brain architecture in the awake monkey. AB - Optical imaging of the functional architecture of cortex, based on intrinsic signals, is a useful tool for the study of the development, organization, and function of the living mammalian brain. This relatively noninvasive technique is based on small activity-dependent changes of the optical properties of cortex. Thus far, functional imaging has been performed only on anesthetized animals. Here we establish that this technique is also suitable for exploring the brain of awake behaving primates. We designed a chronic sealed chamber and mounted it on the skull of a cynomolgus monkey (Macaca fascicularis) over the primary visual cortex to permit imaging through a transparent glass window. Restriction of head position alone was sufficient to eliminate movement noise in awake monkey imaging experiments. High-resolution imaging of the ocular dominance columns and the cytochrome oxidase blobs was achieved simply by taking pictures of the exposed cortex when the awake monkey was viewing video movies alternatively with each eye. Furthermore, the functional maps could be obtained without synchronization of the data acquisition to the animal's respiration and the electrocardiogram. The wavelength dependency and time course of the intrinsic signal were similar in anesthetized and awake monkeys, indicating that the signal sources were the same. We therefore conclude that optical imaging is well suited for exploring functional organization related to higher cognitive brain functions of the primate as well as providing a diagnostic tool for delineating functional cortical borders and assessing proper functions of human patients during neurosurgery. PMID- 1763072 TI - Synaptic background activity influences spatiotemporal integration in single pyramidal cells. AB - The standard one-dimensional Rall cable model assumes that the electrotonic structure of neurons does not change in response to synaptic input. This model is used in a great number of both theoretical and anatomical-physiological structure function studies. In particular, the membrane time constant, tau m, the somatic input resistance, Rin, and the electrotonic length are used to characterize single cells. However, these studies do not take into account that neurons are embedded in a network of spontaneously active cells. Synapses from these cells will contribute significantly to the membrane conductance, especially if recent evidence of very high specific membrane resistance, Rm = 100 k omega.cm2, is taken into account. We numerically simulated the electrical behavior of an anatomically reconstructed layer V cortical pyramidal cell receiving input from 4000 excitatory and 1000 inhibitory cells firing spontaneously at 0-7 Hz. We found that, over this range of synaptic background activity, tau m and Rin change by a factor of 10 (80-7 msec, 110-14 M omega) and the electrotonic length of the cell changes by a factor of 3. We show that this significantly changes the response of the cell to temporal desynchronized versus temporal synchronized synaptic input distributed throughout the neuron. Thus, the global activity of the network can control how individual cells perform spatial and temporal integration. PMID- 1763071 TI - Receptor class desensitization of leukocyte chemoattractant receptors. AB - To better define their regulation, formylpeptide and C5a chemoattractant receptor cDNAs were transiently expressed with high efficiency (approximately 35-54%) in human kidney cells. As in neutrophils, both receptors were active in elevating intracellular calcium (ED50 approximately 0.5-1 nM). Agonist-specific desensitization for calcium elevation was observed for both chemoattractant receptors at doses of approximately 1 nM. Heterologous desensitization of formylpeptide, C5a, and alpha 1-adrenergic receptors required high doses of phorbol ester (100 nM phorbol 12-myristate 13-acetate). To further study the phenomenon of desensitization, formylpeptide and C5a receptor cDNAs were cotransfected resulting in approximately 80% of receptor-positive cells expressing both receptors. These cells also possessed endogenous alpha 1 adrenergic receptors. Interestingly, chemoattractant receptors were cross desensitized by pretreatment with low doses of either C5a or formylmethionylleucylphenylalanine (10 nM) but not by the alpha 1-adrenergic agonist norepinephrine (up to 10 microM). Neither chemoattractant desensitized alpha 1-adrenergic receptors. This phenomenon was reproduced in human neutrophils. These data suggest a previously uncharacterized mechanism of receptor regulation, which is intermediate between homologous and heterologous desensitization. Class desensitization of chemoattractant receptors is less selective than homologous desensitization but is far more efficient and specific than heterologous desensitization. Receptor class desensitization may affect functional classes of receptors via modification of either the receptor or the shared guanine nucleotide-binding regulatory protein. PMID- 1763073 TI - Escherichia coli mfd mutant deficient in "mutation frequency decline" lacks strand-specific repair: in vitro complementation with purified coupling factor. AB - Mutation frequency decline (MFD) is the rapid decrease in the frequency of certain induced nonsense suppressor mutations occurring when protein synthesis is transiently inhibited immediately after irradiation. MFD is abolished by mutations in the uvrA, -B, or -C genes, which prevent excision repair, or by a mfd mutation, which reduces the rate of excision but does not affect survival. Using an in vitro repair synthesis assay we found that although wild-type cells repair the transcribed (template) strand preferentially, mfd- cells are incapable of strand-specific repair. The deficiency in strand-selective repair of mfd- cell extract was corrected by adding highly purified "transcription-repair coupling factor" to the reaction mixture. We conclude that mfd is, most likely, the gene encoding the transcription-repair coupling factor. PMID- 1763076 TI - Who pays for PREPP? AB - Although it is now known that PREPP is to be implemented, there is still much uncertainty as to how it will be funded. Will nurses receive funding for their continuing education needs from health trusts, be expected to self-fund or seek sponsorship from drug companies? PMID- 1763075 TI - Inward-rectifying K+ channels in guard cells provide a mechanism for low-affinity K+ uptake. AB - The molecular mechanisms by which higher plant cells take up K+ across the plasma membrane (plasmalemma) remain unknown. Physiological transport studies in a large number of higher plant cell types, including guard cells, have suggested that at least two distinct types of K(+)-uptake mechanisms exist, permitting low-affinity and high-affinity K+ accumulation, respectively. Recent patch clamp studies have revealed the presence of inward-conducting (inward-rectifying) K+ channels in the plasma membrane of higher plant cells. Research on guard cells has suggested that these K+ channels provide a major pathway for proton pump-driven K+ uptake during stomatal opening. In the present study the contribution of inward-rectifying K+ channels to higher plant cell K+ uptake was investigated by examining kinetic properties of guard cell K+ channels in Vicia faba in response to changes in the extracellular K+ concentration. Increasing the extracellular K+ concentration in the range from 0.3 mM to 11.25 mM led to enhancement of inward K+ currents and changes in current-voltage characteristics of K+ channels. The increase in K+ conductance as a function of the extracellular K+ concentration revealed a K(+) equilibrium dissociation constant (Km) of approximately 3.5 mM, which suggests that inward-rectifying K+ channels can function as a molecular mechanism for low affinity K+ uptake. Lowering the extracellular K+ concentration in the range from 11 mM to 1 mM induced negative shifts in the activation potential of K+ channels, such that these channels function as a K+ sensor, permitting only K+ uptake. At low extracellular K+ concentrations of 0.3 mM K+, inward-rectifying K+ channels induce hyperpolarization. Results from the present study suggest that inward rectifying K+ channels constitute an essential molecular mechanism for plant nutrition and growth control by providing a K(+)-sensing and voltage-dependent pathway for low-affinity K+ uptake into higher plant cells and additionally by contributing to plasma membrane potential regulation. PMID- 1763074 TI - Association of DQw7 (DQB1*0301) with ocular cicatricial pemphigoid. AB - Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and II and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P less than 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class II allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP. PMID- 1763077 TI - Prevention is better than coma. Patient education on diabetic coma. AB - It is well recognised that people with diabetes may have comas at times. A coma is not, however, inevitable, and patient education can enable people with diabetes to recognise situations which may cause them to have a coma, and take preventive action. PMID- 1763078 TI - Diabetes: how to avoid a coma. PMID- 1763079 TI - Euthanasia: the way to a peaceful end? AB - Euthanasia is an emotive subject, and one in which the line between what is legal and illegal is often blurred. Nurses need to tackle the issue personally and professionally to ensure they deliver care that is in their patients' interests. PMID- 1763080 TI - A fighting chance to breathe. Repair of congenital diaphragmatic hernia. AB - Diaphragmatic hernia is a congenital lung defect which has high mortality rates. It can be corrected by surgery if the lungs are not too severely affected, and requires excellent postoperative nursing care. PMID- 1763081 TI - Clinical support in a homely setting. Hostel wards for long-term psychiatric care. AB - Closure of long-stay psychiatric hospitals has posed problems providing for some people with chronic problems. Hostel wards provide homely settings where they can receive intensive therapy to increase their independence. PMID- 1763082 TI - A therapeutic aid in cancer care. Uses of radioisotopes in diagnosis and treatment. PMID- 1763083 TI - Where there's life ... Intensive care for patients with AIDS and HIV. AB - The most common cause of Aids-related death is respiratory failure. Although the mortality rates are high, drug therapy can lead to successful outcomes. By keeping up-to-date with current developments, nurses working in ICUs can help adapt practice to suit individual needs and requirements. PMID- 1763084 TI - Can grief be turned into growth? Staff grief in palliative care. AB - Palliative care nurses can experience profound feelings of grief and helplessness when a patient dies. Staff support can help them work through their feelings of grief and use them as growing experiences. PMID- 1763085 TI - Safety first: the key consideration. Management of clinical waste. AB - Strict protocols are required for the storage and disposal of waste. If staff are alerted to the correct procedures, and protective clothing and equipment is provided, potentially dangerous accidents can be prevented. PMID- 1763086 TI - Incidence and aetiology of leg ulcers. PMID- 1763087 TI - A coordinated programme will identify needs. Practice nurses' role in screening elderly people. AB - The new GP contract requires that practices implement a screening programme for people aged over 75. With training, practice nurses can provide this screening, playing an important role in a coordinated primary healthcare service. PMID- 1763088 TI - He's wearing his glasses again. PMID- 1763089 TI - Dihydropyridine-induced release of catecholamines in cardiac tissue. AB - The symmetrically substituted dihydropyridine-dicarboxylate 3 exerts only weak calcium antagonistic activity on smooth muscles compared with the standard nifedipine. On electrically stimulated, left guinea pig-atria and particularly on electrically stimulated papillary muscles marked positive inotropic effects are registered. They can be attributed to release of catecholamines from intracellular stores. PMID- 1763090 TI - The influence of some anthracene and diphenylmethane derivatives on water and electrolyte movement in rat colon. AB - The secretagogue activity of 30 different anthracene and diphenylmethane derivatives was investigated by determining their influence on water, sodium and potassium absorption in the gastrointestinal tract of the rat by direct administration into the rat colon. To obtain an effect two phenolic groups are necessary. However the distance between these groups seems to be a major factor for secretagogue activity. In the case of the anthranoids an intact anthraquinone or anthrone structure is a prerequisite. PMID- 1763091 TI - Availability and activity of preservatives in emulsified systems. AB - Availability and activity of methyl-p-hydroxybenzoate, phenoxyethanol and chlorocresol in emulsions were studied by equilibrium dialysis and microbiological methods. Equation proposed by Bean and coworkers for calculating the availability of free preservatives in the aqueous phase of simple emulsion was also found to be applicable to modern emulsions composed of more than one oil and surfactant. The antimicrobial activity varied with the type of preservative and microorganism. Among the four test organisms, Pseudomonas aeruginosa and Staphylococcus aureus were more resistant to the various preservatives than Candida albicans and Aspergillus niger. The concentration of free preservative in the aqueous phase of the emulsion required to reduce the microbial population to the level specified in BP was found to be less than the concentration needed in distilled water indicating that the antimicrobial activity of the preservatives in emulsions is not entirely dependent on the concentration of their free form in the aqueous phase of emulsions. PMID- 1763092 TI - [The bioavailability of paracetamol II. The effect of porosity and mechanical properties of the dosage form on solubility]. AB - The authors attempt to explain differences observed in dissolution rate of twelve different brands of paracetamol (nine tablets and three capsules) in terms of pore structure and tensile strength; the pore structure of both tablets and capsules is investigated by mercury porosimetry. Brands (tablets) which liberate paracetamol rapidly are characterized by a higher porosity value. Higher mean pore diameter signifies less t50 and higher porosity. An increase in tensile strength results in an increase in t50 and a decrease in porosity. Porosity alone cannot dictate the dissolution behaviour of capsules. PMID- 1763093 TI - [Medicinal Lamiaceae with antioxidant properties, a potential source of rosmarinic acid]. AB - Hydroalcholic extracts from four native medicinal Lamiaceae, Lycopus europaeus L., Melissa officinalis L., Origanum vulgare L. and Prunella vulgaris L. have shown significant antioxidative activities, by free radical scavenger effect on DPPH, compared with those of Rosmarinus officinalis L. and Salvia officinalis L. extracts. The antioxidative activity was partly in relation to the rosmarinic acid content. The major hydroxycinnamic compound, quantitatively determinated by HPLC, was present in large amount. The content in Prunella vulgaris L. spikes average 6.1%, based on dry weight. PMID- 1763094 TI - Chemical properties-dissolution relationship. IV. Behaviour in solution of the diclofenac/N-(2-hydroxyethyl) pyrrolidine salt (DHEP). AB - The behaviour in solution of the salt formed between diclofenac and N-(2 hydroxyethyl) pyrrolidine (DHEP) was examined. This salt is more soluble and dissolves more rapidly than sodium diclofenac and tends to give rise to supersaturated solutions, that only slowly evolve to equilibrium. Above 35 mM of DHEP, the solutions show unexpected solubilization ability towards sparingly soluble materials. The faster plasma level found, when DHEP is administered per os, can be associated to this weak detergency. These properties make DHEP a suitable pharmaceutical form to prepare extemporary solutions for short term analgesic therapy. PMID- 1763095 TI - Diffusion of naproxen in presence of beta-cyclodextrin across a silicone rubber membrane. AB - The diffusion of Naproxen through a silicone rubber membrane has been studied for four different release systems: solution and suspension both of Naproxen and Naproxen beta-cyclodextrin coprecipitates. Differences in transport between the two forms indicate the existence of an interaction between the acid and beta cyclodextrin in solution. Independence of the transport on pH in the case of the coprecipitate indicates rapid liberation of Naproxen from the complex prior to entering the membrane. Increase in the cumulative amount diffused for the suspension of Naproxen with increasing pH was interpreted as due to an increase in its solubility with increasing pH. PMID- 1763096 TI - Hypothermia and feeding induced simultaneously in rats by perfusion of neuropeptide Y in preoptic area. AB - Changes in the body temperature (Tbo) of the unrestrained rat as well as the hyperphagic-like ingestion of food were simultaneously determined during the sustained elevation of neuropeptide Y1-36 (NPY) within the anterior hypothalamic preoptic area (AH/POA). A single guide tube was implanted stereotaxically in each rat for repeated perfusions by means of push-pull cannulae of either the CSF solvent vehicle or NPY. Following postoperative recovery, each site in the AH/POA was perfused for 6.0 min at a rate of 20 microliters/min over four successive intervals at a concentration of 100 ng/1.0 microliters or 250 ng/1.0 microliters, with an interval of 6.0 min intervening between perfusions. During repeated perfusions of NPY in the fully sated and normothermic rat, concentration dependent eating, or a hypothermia or both responses occurred simultaneously. Mean cumulative intakes of food over 3.0 h were 12.1 +/- 1.4 and 21.5 +/- 2.7 g following the 100 and 250 ng concentrations of NPY, respectively. The mean maximal declines in Tbo were -0.92 +/- 0.21 and -1.1 +/- 0.28 degrees C, respectively after the lower and higher concentrations of the peptide. Push-pull perfusions of artificial CSF control vehicle at homologous anatomical sites in the AH/POA were without effect on feeding or the Tbo of the rats. These results demonstrate that repeated and sustained elevation of NPY in the AH/POA can cause a perturbation of the neuronal mechanisms underlying the normal "set-point" for body temperature as well as satiety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763097 TI - Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane. AB - Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT) and cocaine were compared in squirrel monkeys responding under a second-order schedule of IV drug injection. Both CFT and cocaine maintained self-administration in all subjects. As the dose of either drug was increased, the rate of responding first increased and then decreased. Although the two drugs had qualitatively similar effects, CFT was approximately six times more potent than cocaine. This potency relation corresponds closely with the potency relations reported for CFT and cocaine in studies of dopamine uptake inhibition and binding at cocaine recognition sites. The results are consistent with the view that the reinforcing effects of cocaine-like drugs are mediated at cocaine recognition sites associated with the dopamine uptake system, and suggest that radioligand probes based on CFT may be suitable markers for these sites. PMID- 1763098 TI - Failure to detect increases in brain dopamine metabolism in rats sham feeding sucrose and corn oil. AB - In a recent study we found that when rats sham fed 6% sucrose, 10% sucrose, and 100% corn oil, the rank order of inhibitory potency for D-1 and D-2 receptor antagonists was 6% sucrose greater than 10% sucrose greater than 100% corn oil. In a complementary study, sham-feeding rats preferred 100% corn oil greater than 10% sucrose greater than 6% sucrose as measured by two-bottle preference tests. The preferences are evidence for the rank order of reward value of these solutions. In the present study we tested the hypothesis that the relative antagonist potencies were due to differential release of DA, dependent on the reward value of the sham-fed solution. Dopamine metabolism, estimated by the ratio of dihydroxphenylacetic acid (DOPAC) to DA, was measured in forebrain-DA terminal fields during sham feeding of 100% corn oil, 6% sucrose, and 10% sucrose. The results did not support our hypothesis: no increase in DA metabolism was observed after the sham feeding of any solution. PMID- 1763099 TI - Hypotensive effects of sarthran in normotensive and spontaneously hypertensive rat strains. AB - The specific angiotensin receptor antagonist [Sar1, Thr8]AII (sarthran) was intracerebroventricularly (ICV) infused in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive controls. The results extend earlier findings by determining that: 1) the hypotensive effect of ICV infused sarthran could be enhanced in anesthetized as compared with alert animals; 2) SHRs revealed a greater hypotensive response as compared with WKY rats; and 3) no sarthran-induced agonistic effects were observed in contrast with previous results using alert SHRs. These findings support the use of sarthran as a potent angiotensin receptor antagonist to investigate the role of the brain angiotensin system in the control of normal and dysfunctional blood pressure. PMID- 1763100 TI - Effects of ketamine and 1-glutamic acid diethyl ester on concept learning in rats. AB - The effects of ketamine, an NMDA receptor antagonist, and 1-glutamic acid diethyl ester (LGDE), a non-NMDA glutamate antagonist, were evaluated in the acquisition of concept learning in a water maze. In concept learning, the rats must locate an invisible platform whose location changes from day to day. In spatial learning (Morris task), the rats must locate an invisible (or visible) platform whose location does not change. Ketamine increased quadrant entries at 5, 10 and 20 mg/kg, and latencies at 10 and 20 mg/kg on the final two days of training on the concept task. At 5 mg/kg ketamine disrupted concept learning but not spatial learning or visuo-motor coordination as assessed by invisible and visible platform conditions of the Morris maze. Progressively higher doses of ketamine affected first the invisible condition and then the visible platform condition. On the other hand, LGDE did not affect the Morris task at any dose. However, there was no decrease in latencies over days in concept learning at the two highest doses (240 and 360 mg/kg) of LGDE. Thus LGDE appeared to slow down decision time in the concept task but not the spatial task in the absence of an effect on quadrant entries in any version. These results indicate that NMDA receptors are involved in spatial and concept learning. Non-NMDA receptors appear to be involved only in concept learning. PMID- 1763101 TI - Effects of THA on passive avoidance retention performance of intact, nucleus basalis, frontal cortex and nucleus basalis + frontal cortex-lesioned rats. AB - Unilateral quisqualic acid lesions of the nucleus basalis magnocellularis (NBM) produced marked choline acetyltransferase depletion (-67% ipsilateral to lesion) and impaired passive avoidance (PA) retention at 24 hours. Pretraining injections of tacrine (THA: 1, 3 and 5 mg/kg), an anticholinesterase, failed to facilitate PA retention in intact rats. However, the retention performance of NBM-lesioned rats was improved by pretraining administration of THA at 3 mg/kg but not at either 1 or 5 mg/kg. Frontal cortex lesioning did not impair PA retention, and THA at 3 mg/kg had no effect on the PA retention of frontal cortex-lesioned rats. THA at 3 mg/kg failed to improve retention performance of NBM + frontal cortex lesioned rats. After 10 days of chronic treatment with THA, NBM lesion-induced PA retention deficits were partially restored at both 3- and 5-mg/kg doses. The results suggest that 1) the insult to cholinergic neurons in the NBM may be involved in the PA memory consolidation deficit induced by nonselective quisqualic acid lesioning; 2) the beneficial effects of THA on NBM lesion-induced PA retention deficit occur in a narrow dose range; 3) the alleviating effects of THA on NBM lesion-induced PA memory deficits are blocked by frontal cortex lesions; and 4) the dose-response window for THA-induced PA retention performance improvement is broadened by repeated treatment. PMID- 1763102 TI - Role of histaminergic mechanisms in the regulation of some stress responses in rats. AB - The involvement of histaminergic mechanisms in the regulation of some stress responses was studied in rats. The brain neuronal histamine (HA) depletor, alpha fluoromethyl histidine (alpha-FMH), at doses (50 or 100 mg/kg) which markedly lower brain HA, significantly attenuated the gastric ulcer formation and the elevation in plasma corticosterone in response to cold restraint stress (CRS). alpha-FMH also appreciably reduced gastric mucosal HA content. The H1-antagonist, pheniramine (25 mg/kg), attenuated both the gastric mucosal and endocrine response to CRS, while the effects of the H2-antagonist, cimetidine (200 mg/kg), were on the plasma corticosterone levels. These results are discussed in light of complex HA-ergic mechanisms in the maintenance of physiological homeostasis during stress. PMID- 1763103 TI - On the development of behavioral tolerance to organophosphates. IV: EEGand visual evoked responses. AB - Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were carried out, each consisting of three groups of rats, SC injected with saline, DFP (600 micrograms/kg) or soman (60 micrograms/kg) respectively. In Experiment B and D the rats were trained to criterion in a two-way shuttlebox. Thereafter, the animals of Experiment B were fitted with suitable electrodes and two days later their EEGs and visual evoked responses (VERs) were recorded, 1 and 24 h after a single dose of the above mentioned compounds. In Experiment D the trained animals were subsequently injected 3 times per week for 4 weeks with the same doses and their performance was tested 5 days per week, 1 and 24 h after injection. After those 4 weeks, when the DFP-treated animals had developed behavioral tolerance, electrodes were fitted and EEGs and VERs were recorded after two days, again 1 and 24 h after injection, as in Experiment B. The difference with Experiments A and C was that these animals were not trained. Otherwise, treatment schedules and recording procedures of Experiment A were identical to those of Experiments B and of Experiment C to those of Experiment D. In all cases the EEGs and VERs were recorded from animals slowly walking in a rotating hollow transparent wheel. The results show a similar pattern in all four experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763104 TI - Discriminated taste aversion with chlordiazepoxide. AB - Discriminative stimulus effects have been studied extensively with the two response, food-reinforced operant procedure and more recently also with discriminated taste aversion (DTA) procedures. DTA procedures have the advantage of a more rapid discrimination training. However, the test phase, i.e., drug substitution, of the DTA procedure is more time consuming (1 test per 4 days) than the test phase of the two-response procedure (2 tests per 5 days). The present study investigated whether a DTA procedure with 2 tests per 5 days could be implemented. In addition, the specificity of the DTA procedure was investigated. Rats were trained to discriminate chlordiazepoxide (CDP, 20 mg/kg, IP) from vehicle using a discriminated taste aversion procedure. Selective suppression of saccharin consumption after CDP injections was maximal after seven CDP-LiCl pairings. In subsequent substitution tests, with 2 tests per 5 days, CDP mimicking effects were found only for another benzodiazepine, diazepam, and for a barbiturate, pentobarbital. The results indicate that rats can be rapidly trained to discriminate CDP from vehicle in the discriminated taste aversion procedure and that the CDP-cue so produced has the same specificity as in a two-response, food-reinforced operant procedure. However, the DTA procedure has a number of drawbacks that make its advantage over the two-response procedure questionable. PMID- 1763105 TI - The behavioral effects of heptyl physostigmine, a new cholinesterase inhibitor, in tests of long-term and working memory in rodents. AB - We assessed the effects of heptyl physostigmine, a new cholinesterase inhibitor, in a mouse tail-flick (TF) test, a mouse and rat passive avoidance test, a rat conditioned suppression-of-drinking (CSD) test, a rat Random Interval (RI) response rate test and a rat delayed matching-to-position (DMTP) test. In the TF test, a dose of 8.0 mg/kg of heptyl induced a significant antinociceptive effect that was in excess of 75% of the maximum possible effect 300 minutes after administration. In the mouse passive avoidance test, a dose of 3.0 mg/kg of heptyl fully reversed, and a dose of 1.0 mg/kg partially reversed, a scopolamine induced (0.2 mg/kg) deficit. In the rat passive avoidance test, a dose of 8.0 mg/kg fully reversed a scopolamine-induced (0.2 mg/kg) deficit, while a dose of 4.0 mg/kg of heptyl was without effect. In the same experiment, a dose of 0.6 mg/kg of physostigmine partially reversed the scopolamine-induced deficit. In the CSD test, a dose of 8.0 mg/kg of heptyl fully reversed, and doses of 1.0 and 4.0 mg/kg of heptyl partially reversed, the deficit induced by scopolamine (0.4 mg/kg). In the RI response rate test, doses of 8.0 mg/kg and 0.6 mg/kg of physostigmine fully suppressed lever pressing for food rewards. Doses of 4.0 mg/kg of heptyl and below had no effect on lever-pressing rates. In the working memory test (DMTP), 4.0 mg/kg heptyl partially reversed the scopolamine-induced deficit (0.2 mg/kg) in the number of correct choices made, but did not affect the scopolamine-induced deficit in the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763106 TI - Individual differences in behavioral measures: correlations with nucleus accumbens dopamine measured by microdialysis. AB - Rats were placed in one of two novel test environments for behavioral observation. In one, exploratory behavior (assessed by hole pokes) and locomotion were assessed during a 10-min test session. In the other, the chewing of varied objects on the cage floor was rated over a 20-min session. Within 2-18 days, animals were anesthetized and microdialysis probes were implanted into the nucleus accumbens for measurement of basal and d-amphetamine-stimulated levels of dopamine (DA). These measures were then correlated with the individual behavioral rating collected earlier from the drug-free animals. We found a significant correlation between duration of exploratory behavior and amphetamine-induced DA release. Locomotor activity did not correlated with either basal or amphetamine stimulated DA release. Duration of chewing episodes correlated with basal levels of DA, as well as with amphetamine-induced DA release. Our studies indicate that differences in the dopaminergic responsivity of the nucleus accumbens (or other circuitry influencing nucleus accumbens DA function) may contribute to individual differences in certain behaviors displayed by the animals when placed in a novel environment. PMID- 1763107 TI - The effects of postnatal caffeine exposure on growth, activity and learning in rats. AB - Caffeine is both ingested by pregnant women in their third trimesters and administered therapeutically to premature infants to stimulate respiration. This experiment attempted to delineate any persistent effects of low dose caffeine exposure during the first week of life in rats, since this time period provides an animal model equivalent to the human third trimester or premature infant exposure. Rat pups who had received either 1 or 9 mg/kg of caffeine during the first week of life grew more slowly, were hypoactive at two weeks of age, and were impaired on an operant spatial learning task as adults. Adding visual cues to the operant task did not improve their performance. The timing of the appearance of developmental landmarks, adult body weight and adult brain weight, however, were not affected by postnatal caffeine exposure. The persistent behavioral deficits noted after postnatal caffeine exposure were all opposite in direction to the acute effects of caffeine, and similar to the effects of adenosine. Thus the behavioral deficits reported here may reflect an upregulation of developing adenosine receptors that persists into adulthood subsequent to early chronic postnatal caffeine exposure. PMID- 1763108 TI - Subjective and brain-evoked responses to electrical pain stimulation: effects of cigarette smoking and warning condition. AB - Infrahuman studies employing behavioral indices of pain reactivity have supported a central antinociceptive action of nicotine which appears to be selective and dependent on the class of pain elicited. Human investigations employing subjectively based ratings and judgments of pain intensity have been less conclusive regarding the painfulness of stimuli following nicotine/smoking administration. As the more objective brain-evoked potential (EP) measure has been shown to reflect pain intensity and to be sensitive to a variety of analgesics, this study attempted to examine, together with subjective responses, the effects of cigarette smoking on EPs to pain stimuli administered under varying warning conditions. Twelve male and twelve female smokers served as experimental subjects. In smoking and nonsmoking sessions, subjective intensity ratings (SR) and vertex EPs were assessed in response to electrical skin stimuli presented at a level 20% above pain threshold. Stimulation was either nonwarned or warned with warning conditions involving single or repeated presentations of electrical current at constant or increasing intensities 12 seconds prior to pain stimulation. SRs and peak-to-peak N1-P2 EP amplitudes were measured for each smoking session and warning condition. A significant condition effect was observed for SRs with increasing prepain warning stimulation resulting in the greatest pain ratings. Although smoking did not directly alter SRs or EPs to pain, smoking exposure, as measured by carbon monoxide, was found to be differentially correlated with EP alterations in male and female smokers depending on the warning condition. PMID- 1763109 TI - Effects of pimozide on the hedonic properties of sucrose: analysis by the taste reactivity test. AB - The ability of the neuroleptic agent, pimozide, to modify sucrose palatability was assessed using three 10-min taste reactivity test sessions. Pimozide was found to suppress the ingestive response of tongue protrusions, but enhance the mildly ingestive/neutral response of mouth movements elicited by an intraoral infusion of sucrose solution. Since the pattern of taste reactivity responding shifted from highly ingestive to mildly ingestive/neutral, our results suggest that pimozide pretreatment reduces the palatability of sucrose solution. The temporal pattern of the modification of these taste reactivity responses was predicted by the Anhedonia Hypothesis. PMID- 1763110 TI - Effects of systemic and intra-amygdaloid diazepam on long-term habituation of acoustic startle in rats. AB - Two experiments were conducted to examine the effects of the anxiolytic drug, diazepam, on long-term habituation of the acoustic startle response. The experiments were based upon the hypothesis that manipulations that reduce fear should enhance long-term response decrements by reducing a fear-like sensitization process. In Experiment 1 rats given intraperitoneal injections of 0.5, 1.2, or 2.5 mg/kg showed larger decrements of startle amplitude than vehicle injected controls both over trials within sessions and over days. In Experiment 2 rats injected with 35 micrograms of diazepam bilaterally into the amygdala showed larger decrements of startle amplitudes over days than vehicle-injected controls. No within-session startle effects were detected in Experiment 2. Freezing behavior was measured in Experiment 2 as an index of fear, and the amygdala injections of diazepam retarded the development of fear in the startle chamber. This index of fear was not possible in Experiment 1 because of the sedating effects of systemic diazepam. We conclude that diazepam, acting at least in part through the amygdala, attenuates the fear-like sensitization process associated with the acoustic startle stimulus. By attenuating sensitization diazepam produces larger than normal reductions in startle amplitudes over trials and days without significantly affecting initial responsiveness. PMID- 1763111 TI - Learning factor in rapid tolerance to ethanol-induced motor impairment. AB - Exposure of male Wistar rats to a single moderate dose (1.7 g/kg, IP) of ethanol (EtOH), followed by intensive intoxicated practice on the moving belt apparatus (a total of 12 min during the first hour after EtOH injection), results in functional tolerance to the motor-impairing effects of a second dose given either 8 or 24 h later. In the absence of intoxicated practice, or after a considerably reduced opportunity for it (a total of 4 min during the first hour after EtOH injection), the same dose of EtOH fails to produce tolerance. Thus, not only the opportunity to practice, but also its extent and possibly its quality are important determinants in the rapid development of intersessional tolerance. In contrast to its rapidity of development, no significant loss of this tolerance is evident three weeks after the tolerance acquisition sessions. PMID- 1763112 TI - Sex differences in locomotor activity after acute and chronic cocaine administration. AB - Adult, intact and gonadectomized male and female Wistar rats (n = 9) were exposed to an automated open field to assess the behavioral effects of acute cocaine administration (saline, 1.0 and 10.0 mg/kg subcutaneous). The subjects were exposed to the open field for 10 min, removed to be injected and returned to the open field for another 30 min. Three saline and two drug sessions were run in counterbalanced order. Locomotor activity in intact and castrated male rats and ovariectomized female rats decreased following injection, irrespective of the dose of cocaine. The locomotor activity of intact female rats was higher than that of any other group of subjects. It decreased during the session after saline and 1.0 mg/kg cocaine, but increased towards the end of the 30 min session after 10.0 mg/kg. Rearing measures paralleled the observations on locomotor activity. To determine the effects of chronic, home-cage, cocaine administration, five of the subjects in each group were injected with 10.0 mg/kg cocaine for 9 consecutive days. The remaining four subjects received saline injections. On day 10, all subjects were re-exposed to the open-field for 10 min, removed, injected with 10.0 mg/kg cocaine and returned to the open field for another 30 min. Chronic home cage cocaine administration produced an increase in cocaine's effects on locomotor activity and rearing in intact female rats only. However, behavioral sensitization was also observed in intact female rats who had been treated with saline for 9 consecutive days, suggesting that behavioral sensitization to cocaine in intact female rats may develop very rapidly and independent of environmental context. PMID- 1763113 TI - Effect of a single dose of an acetylcholinesterase inhibitor on oxotremorine- and nicotine-induced hypothermia in mice. AB - Downregulation of cholinergic receptors is a consequence of subchronic exposure to an organophosphate anticholinesterase. The purpose of this investigation was to determine if there was a downregulation of the cholinergic receptors in mice following administration of a single dose of soman (pinacolyl methylphosphonofluoridate) or physostigmine. The change in the temporal response (mean minimum temperature and area under the curve) of core temperature following administration of either a muscarinic or nicotinic agonist such as oxotremorine (156 micrograms/kg, IP) or nicotine hydrogen tartrate (15 mg/kg, SC) was used as an indicator of downregulation of muscarinic or nicotinic receptors, respectively. Twenty-four h following soman (100 micrograms/kg, SC) administration, there was a significant decrease (p less than 0.05) in oxotremorine- but not nicotine-induced hypothermia. The significant differences in the mean minimum temperature and AUC were still present 4 days after exposure to the soman. Neither lower doses of the organophosphate anticholinesterase, soman (50 and 70 micrograms/kg), nor the carbamate anticholinesterase, physostigmine (500 micrograms/kg), produced a significant change in either oxotremorine- or nicotine-induced hypothermia. The results of this study suggest that receptor downregulation observed after subchronic administration of soman is also evident following administration of a single, sublethal dose of an organophosphate anticholinesterase, soman, but not after administration of a carbamate anticholinesterase, physostigmine. The in vivo assessment of the muscarinic receptor using oxotremorine hypothermia may be a sensitive indicator of the functionality of the drug-receptor coupling and indicate a physiological consequence of receptor downregulation. PMID- 1763114 TI - The effects of scopolamine and cues to forget on pigeons' memory for time. AB - Pigeons were trained with a 0-s delayed symbolic matching-to-sample procedure to indicate whether a houselight sample stimulus was short (2 s) or long (8 s) by pecking a red or a green comparison stimulus. In Experiment 1, the pigeons received injections of scopolamine hydrobromide (0.015 mg/kg), or saline, and the delay interval was manipulated (0, 1, 3, and 9 s). Memory for time was significantly poorer following scopolamine injections than following saline injections. A significant choose-short bias was observed under scopolamine at delays as brief as 3 s, but not under saline. In Experiment 2, a brief postsample cue (a vertical or horizontal line) signaled whether the comparison stimuli would be presented or omitted on each trial. During training, comparison stimuli were always presented following the remember (R) cue, but never following the forget (F) cue. During testing, memory for time was significantly poorer on F-cue trials than on R-cue trials. A significant choose-short bias was observed on F-cue trials at the 5- and 10-s delays, but not on R-cue trials. The results suggest that anticholinergic blockade accelerates the rate at which memory for temporal events is foreshortened in working memory. This effect is similar to that produced by an explicit cue to forget the temporal sample. PMID- 1763115 TI - Dynamic properties of respiratory timing following cocaine administration. AB - We assessed the timing and amplitude characteristics of diaphragmatic muscle activity following administration of intravenous cocaine HCl (10 mg/kg) to awake, unrestrained cats. Cocaine produced a pronounced tachypnea which was interrupted by deep inspiratory efforts coincident with tonic-clonic movements over the first 10 min following cocaine administration. Following that period, diaphragmatic cycle rates slowly increased for up to 1 h and were interrupted occasionally by longer inspiratory efforts which were not associated with other overt motor activities. As respiratory rate increased, breath-to-breath variability decreased, and the incidence of deep inspiratory efforts decreased. As total cycle time decreased, the ratio of inspiratory time to expiratory time remained the same between precocaine and early, intermediate and late intoxication periods. The amplitude of diaphragmatic EMG activity increased with the extreme tachypnea. A number of neural mechanisms may mediate the changes in diaphragmatic muscle activity, including hyperthermia and alteration of rostral brain influences on brainstem timing mechanisms. PMID- 1763116 TI - Comparison of the effects of repeated oral versus subcutaneous fenfluramine administration on rat brain monoamine neurons: pharmacokinetic and dose-response data. AB - The importance of the route of drug administration (oral vs. subcutaneous) on the neurochemical effects and pharmacokinetics of repeated d,1-fenfluramine administration in rats (1-24 mg/kg b.i.d., i.e., 2-48 mg/kg/day for 4 days) was examined. Overall, comparable dose-dependent alterations in brain monoamine markers were observed following repeated oral (PO) and subcutaneous (SC) administration of fenfluramine. Doses of 1 and 2 mg/kg fenfluramine were without significant effects on the density of 3H-paroxetine-labeled serotonin (5-HT) uptake sites. Higher doses of fenfluramine (4, 12 and 24 mg/kg) produced dose dependent decreases in 5-HT, 5-hydroxyindoleacetic acid and 5-HT uptake sites with maximal decreases (80-90%) occurring at the 12 mg/kg dose. Fenfluramine administration produced dose-dependent and biphasic effects on brain dopamine markers with increases in homovanillic acid (HVA) observed at 2 hours, whereas decreases in the levels of dopamine, HVA and dihydroxyphenylacetic acid were evident at 18 hours posttreatment. Norepinephrine levels were only decreased at the highest dose of fenfluramine. Significantly higher levels of brain fenfluramine were observed following SC than following PO administration of the drug. On the other hand, comparable levels of its active metabolite norfenfluramine were present in the brain following the two routes of fenfluramine administration. These data suggest the importance of norfenfluramine levels in the brain in determining the high-dose neurotoxic effects of fenfluramine on brain 5-HT neurons in rats. PMID- 1763117 TI - Nasal pungency, odor, and eye irritation thresholds for homologous acetates. AB - We measured detection thresholds for nasal pungency (in anosmics), odor (in normosmics) and eye irritation employing a homologous series of acetates: methyl through octyl acetate, decyl and dodecyl acetate. All anosmics reliably detected the series up to heptyl acetate. Only the anosmics without smell since birth (congenital) reliably detected octyl acetate, and only one congenital anosmic detected decyl and dodecyl acetate. Anosmics who lost smell from head trauma proved to be selectively less sensitive. As expected, odor thresholds lay well below pungency thresholds. Eye irritation thresholds for selected acetates came close to nasal pungency thresholds. All three types of thresholds decreased logarithmically with carbon chain length, as previously seen with homologous alcohols and as seen in narcotic and toxic phenomena. Results imply that nasal pungency for these stimuli rests upon a physical, rather than chemical, interaction with susceptible mucosal structures. When expressed as thermodynamic activity, nasal pungency thresholds remain remarkably constant within and across the homologous series of acetates and alcohols. PMID- 1763118 TI - Visual recognition memory in squirrel monkeys: effects of serotonin antagonists on baseline and hypoxia-induced performance deficits. AB - Cognitive deficits resulting from neuropathological brain changes such as Alzheimer's Disease or normal aging are most likely due to alterations in multiple neurotransmitter systems. While the majority of preclinical studies have focused on the effects of acetylcholine (ACh), it has been shown that activation of the serotonergic (5-HT) pathways in the central nervous system interferes with passive avoidance retention in rats. In contrast, decreased 5-HT activity has been shown to improve learning and memory in rats using similar procedures. In the present experiment, 5-HT antagonists were evaluated for their effects on performance in a delayed match to sample task (DMTS) in two groups of squirrel monkeys: one in which the baseline level of performance was low (less than 65% correct, N = 5; group 1) and another in which DMTS performance was high (greater than 80% correct, N = 3; group 2) but impaired by exposure to hypoxia. Initial parametric tests exposing group 2 to various levels of oxygen deprivation were conducted to determine optimal conditions for performance deficits. Each monkey in both normoxia (group 1) and hypoxia (group 2) served as his own control and received an individualized range of doses for each test compound. For both groups, ketanserin and mianserin, the 5-HT2-selective antagonists, produced dose dependent increases in DMTS performance at 0.3-1.5 mg/kg PO and 0.05-1.5 mg/kg PO, respectively. Pirenperone, another 5-HT2-selective antagonist, was active in improving performance in group 1 at 0.001 to 0.2 mg/kg PO but was not effective against hypoxia-induced performance deficits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763119 TI - Naftidrofuryl oxalate, nootropic effects on the scopolamine- and the basal forebrain lesion-induced amnesia in rats. AB - We studied the effects of naftidrofuryl oxalate on scopolamine- and basal forebrain (BF) lesion-induced amnesia using passive avoidance and multiple T-maze tasks, in comparison with Ca-hopantenate and physostigmine in rats. In the passive avoidance task, one-week treatment with naftidrofuryl oxalate (12.5 and 25 mg/kg, IP) ameliorated BF lesion-induced amnesia. The multiple T-maze task was done with two training sessions per day for five continuous days. We measured the number of errors made from start box to goal box. Naftidrofuryl oxalate (12.5 mg/kg, IP, b.i.d.) and physostigmine (0.1 mg/kg, IP, b.i.d.) attenuated scopolamine- and BF lesion-induced amnesia. However, treatment with naftidrofuryl oxalate for one week failed to inhibit the decrease of the choline acetyltransferase induced by the BF lesion. Ca-hopantenate did not show attenuation of amnesia induced by the scopolamine or BF lesion. These results suggest that naftidrofuryl oxalate enhances the storage of spatial information, and that the nootropic effects of naftidrofuryl oxalate may be produced by an indirect activation of the cholinergic system through serotonergic neuronal systems. PMID- 1763120 TI - [Phenytoin and phenytoin derivatives for local administration]. AB - A well known side effect of the long-term therapy with phenytoin is gum hyperplasia. 1-Acyl compounds and esters of the p-hydroxymetabolite with aliphatic and aromatic carboxylic acids were synthesized as potential prodrugs for therapeutic use if the neoformation of connective tissue is intended. The compounds were characterized by there physico-chemical constants and the absorption was proofed by a buccal test. PMID- 1763121 TI - [Pharmaceutical technology texts and criteria for evaluation of their intelligibility]. AB - This article gives a report on the criteria of the intelligibility of texts and on the possibility of their evaluation. With the help of these criteria it becomes possible to describe different levels in the pharmaceutical communication. Their conscious construction may promote the understanding of texts. PMID- 1763122 TI - [Defined cyclic doses (DCD)--a proposal for the application of the DDD method to the antineoplastic group]. AB - The establishment and implementation of defined daily doses (DDD) has provided a useful tool to compare drug consumption studies on regional as well as international level. One of the limitations of the concept so far is the fact that according to the definition of the DDD there are no DDDs for certain groups of drugs like antineoplastic drugs. In order to close that methodological gap we suggest a special technical unit of measurement with regard to the therapeutical routine of application of antineoplastic drugs: the defined cycle dosis (DCD). That the DCD can be applied to comparing the consumption of antineoplastic drugs in principle is shown by means of statistical data covering the years from 1983 to 1988 in East Germany. PMID- 1763123 TI - [Synthesis and antiphlogistic activity of amino- and nitro-substituted DL phenylamino acid octylester hydrochlorides]. PMID- 1763124 TI - [The effect of drugs on the in vitro detection of glucose in urine with the Benedict test]. PMID- 1763125 TI - Determination of pentazocine in human plasma by high performance liquid chromatography. PMID- 1763126 TI - Determination of captopril by two simple spectrophotometric methods using oxidative coupling reaction. PMID- 1763127 TI - [The use of isolated and cultivated lymphocytes of rats for the study of biotransformation of drugs]. PMID- 1763128 TI - Pharmacokinetic investigations with dexamethasone megadoses in rats. PMID- 1763129 TI - Comparison of the effect of stobadine on lipid peroxidation of liver, heart, kidney and brain homogenate. PMID- 1763130 TI - Effect of kampo medicines on lipid peroxidation of phosphatidylcholine liposomes. PMID- 1763131 TI - [The effect of (+) and (-)-propranolol in high doses on selected heart circulatory parameters in the rat]. PMID- 1763132 TI - Cytotoxic activity of sesquiterpene lactones, isolated from Ambrosia maritima. PMID- 1763133 TI - [The biochemical basis of pharmaceutical chemistry. 11(1). Stereochemical aspects of active drug substances]. PMID- 1763134 TI - Biological and NMR markers for cancer. AB - The search for a universal tumor marker continues. Present markers range from tumor products (polyamines, glycoproteins, peptides, hormones or carbohydrate linked markers) to reaction products produced by the host tissues during tumor invasion. Techniques used to identify them include the classical methods of histology and cytochemistry as well as the more recent radioimmunoassay and metabolic probes. The in vivo techniques of increasing use for patient monitoring are MRS (magnetic resonance spectroscopy) and MRI (magnetic resonance imaging). The efficiency of some markers and statistical methods used in analyzing data are discussed, as are the ethical problems surrounding the use of new testing methods. Recent developments in MRI and MRS, marker elucidation, and evidence for a new autocrine differentiation-inhibiting factor (ADIF) are reviewed. Future needs and approaches focus on greater utilization of indicators of the preneoplastic state and of risk to cancer, as well as more careful attention to statistical analysis. PMID- 1763135 TI - The drug interaction potential of ranitidine: an update. AB - Ranitidine is a H2-receptor antagonist widely used in the treatment of a variety of gastrointestinal disorders. Since cimetidine--the predecessor drug of ranitidine--interacts with a variety of other agents and moreover ranitidine is often administered in combination with other drugs the interaction potential of ranitidine has been subject to extensive investigations. This review updates the information available from 1988 to present. Pharmacokinetic interactions of ranitidine with other drugs may occur at the site of absorption, metabolism and renal excretion. Most of the interactions reported at each of the three levels are minor and of low clinical significance. In view of some uncontrolled anecdotal reports, one cannot completely rule out the possibility that ranitidine might have some limited interaction potential in special patient populations under certain clinical conditions. However, it must be emphasized that numerous controlled studies have proven that ranitidine can be safely coadministered with other drugs. PMID- 1763136 TI - The potential use of catalytic RNAs in therapy of HIV infection and other diseases. AB - This article describes the applications (both real and potential) of a new antiviral strategy, based on the use of antisense, catalytic RNAs (ribozymes) as therapeutic agents. An understanding of both antisense inhibition of gene expression and RNA autocleavage reactions are essential to the use of this technology. In addition, for the successful application of this technology in clinical settings, an interdisciplinary approach involving clinicians, molecular and cellular biologists, will be necessary. The following treatise will highlight several salient features of ribozyme technology, emphasizing its application as an antiviral as well as discuss some problems and potential solutions pertinent to the clinical application of this technology. PMID- 1763137 TI - Regulatory functions of calmodulin. AB - Calmodulin is a Ca2+ binding protein present in all eukaryotic cells that serves as the primary intracellular receptor for Ca2+. This 148 amino acid protein is involved in activation of more than 20 enzymes which mediate a wide variety of physiological processes. Many of these enzymes are inhibited in an intramolecular manner and the Ca(2+)-calmodulin complex relieves this inhibition. Calmodulin is essential for life as disruption of the gene in genetically tractable organisms is lethal. This protein plays important regulatory roles in cell proliferation and is required at multiple points in the cell cycle. The mechanism of enzyme activation by calmodulin and its importance in cell growth regulation are reviewed. PMID- 1763138 TI - Fact sheet on mental health. PMID- 1763139 TI - Of helping relationships: a concept paper. AB - As professionals engaged in the practice of nursing, our involvement with people in different situations provides us many opportunities to be of significant help to them. People are often motivated to enhance themselves. It is the aim of this paper to present a concept in helping relationships that may assist nurses towards a positive direction in helping other people, whether sick or well to improve themselves, to achieve growth, realize their potentials and/or limit their disabilities. PMID- 1763140 TI - The current status of psychiatric/mental health nursing--and some future challenges. International Council of Nurses. PMID- 1763141 TI - Brigadier General Elvegia R. Mendoza: first woman (nurse) general of the armed forces of the Philippines. PMID- 1763142 TI - Importance of pharmacologic control in PET studies: effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia. AB - This study compares the effects of two neuroleptic drugs with different pharmacologic characteristics (thiothixene and haloperidol) on cerebral glucose utilization in chronic schizophrenic inpatients. Positron emission tomographic (PET) scans were obtained from all subjects in a neuroleptic-free condition and again after 4-6 weeks of neuroleptic treatment. Eight subjects were treated with thiothixene and 12 with haloperidol. Thiothixene and haloperidol had different metabolic effects. For example, all thiothixene-treated subjects showed increased whole brain glucose utilization; all but one haloperidol-treated subject showed decreased utilization. Different patterns of relative prefrontal and striatal metabolism were also observed. These results highlight the importance of controlling for the effects of neuroleptic treatment and indicate the difficulty of interpreting data from studies with complex or poorly defined drug regimens. PMID- 1763143 TI - Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients. AB - Since neuroleptic treatment produces a significant increase in striatal metabolism relative to cortical metabolism, we wished to determine whether the dopamine agonist apomorphine (APO) might have the opposite effect, and whether it would discriminate schizophrenic patients from healthy controls. Eleven neuroleptic-naive schizophrenic patients (diagnosed according to DSM-III) and eight normal subjects were compared with respect to cerebral accumulation of 18F fluorodeoxyglucose measured by positron emission tomography following APO, 0.75 mg/70 kg (weight adjusted), or saline. Relative striatal glucose metabolism decreased significantly after APO in schizophrenic patients but not in control subjects. Post hoc analysis of data in 12 other regions revealed that relative superior temporal metabolism decreased very slightly, but significantly, in schizophrenic patients but not in control subjects after APO, and that the posterior frontal region increased in control subjects but not in the patient group. PMID- 1763144 TI - A magnetic resonance imaging study of putamen nuclei in major depression. AB - The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T2 intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression. PMID- 1763145 TI - The psychoanalytic theories of Melanie Klein and Donald Winnicott and their interaction in the British Society of Psychoanalysis. PMID- 1763146 TI - Gender stereotyping in supervisory styles. PMID- 1763147 TI - On Aphasia at 100: the neuropsychodynamic legacy of Sigmund Freud. PMID- 1763148 TI - The working alliance: current concepts and controversies. PMID- 1763149 TI - The addiction to negativity. AB - In this paper, we have described a type of resistance that has attracted increasing psychoanalytic attention in recent years. Patients exposed to intense negativity during early life may develop an addiction to negative experience as adolescents and adults, and this may constitute a central organizing feature of their personality. In almost all patients, however, some moments of negativity may be observed. We have traced the developmental origins of an attachment to negativity, drawing especially on psychoanalytic investigations of preoedipal pathology. Manifestations and derivatives of early negativity include anhedonia, attachment to physical pain, fear of success, masochism, deprivation of self and others, and negative voyeurism. In discussing the dynamic functions of negativity, we place particular emphasis on two motives: the patient's desires for revenge against early objects that have been a source of deprivation and frustration; and the defensive function of negativity in helping to express as well as ward off dangerous wishes to merge with the object. Deviant forms of autoerotism are likely to be used by these patients to deal with the reactivation of early experiences of neglect and rejection. When negativity is used as a defense or method of relating to others it can lead to a severe disruption of the psychotherapeutic relationship. We have reviewed suggestions for the management of extreme negativity in treatment. Resolution of the therapist's countertransference reactions, especially induced feelings of frustration, rage, and helplessness, is crucial. Emphasis also has been placed on the patient's desires for revenge against self and object, and the manner in which these may be understood and eventually resolved. Only when patient and therapist begin to investigate the adaptive functions of extreme negativity can this pathological symptom be resolved and the patient's awareness of self and sense of autonomy be enhanced. PMID- 1763150 TI - Pornography and the primal scene: a report on the voyage to Brobdingnag. PMID- 1763151 TI - Retrospective treatment of incest victims: suggested analytic attitudes. AB - This paper includes a brief consideration of literature relevant to childhood sexual abuse detection and prevalence. That literature indicates that such detection may be difficult and that the occurrence of childhood sexual abuse is widespread. These findings, as well as a consideration of literature relevant to trauma, stress, and the identification of survivors of sexual abuse, suggest an analytic attitude of receptivity to the hypothesis of the event of sexual abuse as well as the fantasy of sexual abuse. A second analytic attitude suggested concerns diagnosis. Childhood trauma is implicated in the development of BPD, as the majority of borderline patients have experienced the trauma of child abuse. Further, trauma can lead to dissociation as a defense against stress, and multiple personality disorder is an extreme example of dissociation. The analytic attitude suggested here is that the diagnosis of BPD or MPD may be a necessary but not a sufficient explanation when the symptomatology is a defensive reaction to the traumatic event of childhood sexual abuse. Lastly, it is suggested that the abuse may need to be central to the treatment in analytic work with sexually abused victims. This is suggested in light of the importance of recovery and integration of traumatic memories with their associated affects. PMID- 1763152 TI - Imagination and the unconscious: a critique of the neo-romantic program. PMID- 1763153 TI - Freud's quotation from Virgil. PMID- 1763154 TI - Between hermeneutics and science. An essay on the epistemology of psychoanalysis. PMID- 1763155 TI - A measure of linear influence between patient and therapist. AB - This paper describes the application of the cross-correlation function (CCF) to four quantified dimensions of the therapeutic consultation dialogue: newness of themes, degree of narration, and positive and negative thematic tone of images. A 10-min. window was used to study lag relationships in both directions of effect- from therapist to patient and the reverse. This measure of linear influence was applied to six psychotherapeutic consultation sessions carried out by different well known psychoanalysts with two women patients. Analysis showed a range of significant CCF effects that totaled from zero to 1360 sec. depending on the consultation. The implications of these and other findings are discussed in the context of viewing the present study as part of a program of investigations into the nonexperimental nature--the underlying laws, structures, and transactions--of therapeutic and everyday emotional dialogues. PMID- 1763156 TI - Relationships between steps taken in selecting a nursing home and consumers' satisfaction. AB - Analysis of data related to selection of a nursing home by 411 families of nursing home residents led to the conclusion that steps selected and taken by consumers in the selection of a home were associated with their subsequent satisfaction with the home. Satisfaction was greater (a) for families in agreement about the home selected and (b) for families who investigated all homes in an area before selecting one. Less satisfied were families (a) who were forced to make an immediate decision about placement following illness of a patient, (b) who felt they lacked sufficient time to investigate homes, and (c) who chose the first home with space available. PMID- 1763157 TI - National measures of extraversion and neuroticism and suicide and homicide rates. PMID- 1763158 TI - Religion as a cultural phenomenon, and national mortality rates from heart disease. AB - An hypothesis is developed which proposes that mortality rates from heart disease are a function of a nation's dominant religious tradition, with predominantly Catholic countries having lower rates than the more Protestant countries. The hypothesis was tested on data from 24 economically developed Western countries. A significant inverse relationship of -0.588 was found between the proportion of Catholics in the 24 nations and mortality rates from heart disease, which supports the hypothesis. PMID- 1763159 TI - Psychology of the scientist: LXIV Work-related attitudes of U.S. scientists. AB - It is logical to think that doing important, meaningful work contributes to job satisfaction. In contrast to all other professional workers, however, evidence from nationwide surveys shows that scientists are more likely to prefer important, meaningful work but are less satisfied in their jobs. This suggests that various factors in the work environment of U.S. scientists somehow may prevent them from achieving the satisfaction they desire in their jobs. This paper speculates about the nature of some of these factors. PMID- 1763160 TI - MMPI experimental scale correlates of the MAACL--R with male alcoholics. AB - Concurrent and discriminative validity of the MAACL--R scales were studied by means of correlations with selected MMPI experimental scales (AR, DR, HOS, Poor Morale, and ES) for a sample of 88 male VA alcoholics. Concurrent validity of Anxiety, Depression, Hostility and PASS, and discriminative validity of the Anxiety scale were confirmed. PMID- 1763161 TI - Parental identification of rapists and pedophiles. AB - It is well documented that sex offenders experience a higher incidence of sexual abuse and are more likely to have been reared in dysfunctional families than are individuals in most comparison groups. It is unclear, however, whether growing up in an abusive or dysfunctional family affects the extent to which the potential sex offender would subsequently identify with his parents. Sixteen rapists, 18 pedophiles, 9 general offenders, and 11 college students completed the Parental Identification Scale to assess their parental identification. It was predicted that the rapists and pedophiles would identify less with their parents than would college students or general offenders. Analysis indicated a strong and significant correlation between group membership and parental identification. Rapists and pedophiles identified less with their mothers and fathers than did members of corresponding control groups. PMID- 1763162 TI - Fakability of two different role-play methodologies for assessing assertion. AB - The fakability of two methodologically different role-play tests of assertion was examined, 30 undergraduates low in assertiveness were tested and retested on the Behavioral Assertiveness Test--Revised and the Idiographic Role-play Test. Half of the testees were instructed to fake assertion during the second testing. Analysis indicated that both tests were fakable; however, testees reported more difficulty faking the latter test than the former. The detection of faking may be possible, particularly on role-play tests employing an idiographic methodology. PMID- 1763163 TI - Influences of situation-specific mastery beliefs and satisfaction with social support on appraisal of stress. AB - Previous research on the effects of mastery beliefs on appraisal of stress usually employed generalized measures such as locus of control and produced mixed findings, depending, in part, on whether the encounters experienced were within the domains of control assessed. The present study examined the effects of situation-specific mastery and satisfaction with social support on the appraisal of a situation's stressfulness by 147 male college students. Mastery was positively correlated with the appraisal of desirability of the situation and accounted for 36.9% of the variance. Greater satisfaction with social support was related to more positive appraisals by subjects with high mastery but with more negative appraisals by subjects with low mastery. Mastery and satisfaction with support also interacted to moderate the effects of the number of stressors experienced on total stress. For subjects who faced many stressors, those with low mastery experienced high stress regardless of their satisfaction with support, whereas those with high mastery experienced high stress if their satisfaction with support was low, but moderately low stress if satisfaction with support was high. PMID- 1763164 TI - Historical reliability: a key to differentiating populations among patients presenting signs of multiple personality disorder. AB - The clinical value of inconsistencies in the historical data of patients presenting with signs of multiple personality disorder was assessed. Three major inconsistencies in historical data were identified in 23 patients who were admitted to a Dissociative Disorders Program with a diagnosis of Multiple Personality Disorder. This group showed psychological disturbance that was quite different from 23 patients with a similar discharge diagnosis but who did not exhibit inconsistencies in history. The former group reported less psychological disturbance and fewer dissociative experiences. Patients who are less credible by virtue of inconsistencies in their historical reports may belong to a different diagnostic group. The findings point to the need to chart history carefully in authenticating genuine cases. PMID- 1763165 TI - Bulimics' perceptions of emotional responding during binge-purge episodes. AB - The concept of changes in emotional arousal during the binge-purge cycle plays a principal role in bulimia theory. Female bulimic patients (n = 29) retrospectively rated the intensity of several emotions during their binge-purge cycle. When collapsed into positive versus negative emotion categories, both categories showed significant changes in emotions over the course of the binge purge episode. Negative emotion increased after a binge and decreased during the purge. Positive emotion decreased after binging and increased during and after purging. PMID- 1763166 TI - Psychology of computer use: XXIV. Computer-related stress among technical college students. AB - Hudiburg's Computer Technology Hassles Scale, along with a measure of global stress and a scale on attitudes toward computers, were administered to 186 students in a two-year technical college. Hudiburg's work with the hassles scale as a measure of "technostress" was affirmed. Moderate, but statistically significant, correlations among the three scales are reported. No relationship between the hassles scale and achievement as measured by GPA was detected. PMID- 1763167 TI - The Basic HIV Disease Knowledge Questionnaire: a Rasch-scaled instrument to measure essential HIV knowledge. AB - The need for improvement in HIV disease-related psychometric questionnaires is noted. In response to this need a Rasch-scaled measure to ascertain basic HIV disease knowledge was developed and calibrated on 1092 subjects. Four studies conducted with the measure suggest adequate test-retest reliability. Three validity studies also conducted with this questionnaire suggest that the measure is sensitive to knowledge obtained from HIV-related training and education. Potential uses and limitations of this new questionnaire are discussed. PMID- 1763168 TI - Symptom-positively and -negatively worded items in two popular self-report inventories of anxiety and depression. AB - Substantially higher mean scores on symptom-negatively versus symptom-positively worded items have consistently been reported in the literature for the balanced State-Trait Anxiety Inventory. In this study we aimed to replicate and extend these findings to Dutch trait versions of the inventory and Zung's similarly balanced Self-rating Depression Scale. Analysis indicated significantly higher mean subscale scores for symptom-negative as opposed to symptom-positive items of both measures, across sexes and age groups as well as across different levels of distress in nonclinical (n = 863), subclinical (n = 450), and clinical subject samples (n = 96). Sex and age differences were mainly confirmed to symptom positive subscales. Scale intercorrelations were lowest between symptom positively and symptom-negatively worded scales both within and across measures. Factor analyzing the combined measures identified a symptom-negative and a symptom-positive factor, tentatively labeled "absence of positive affect" and "presence of negative affect." Several explanations of the findings among which item-intensity specificity, the response style of social desirability, and the trait model of positive and negative affectivity are discussed. PMID- 1763169 TI - Differences between men and women on stress producers and coping strategies. AB - Differences in stress producers and coping strategies for 158 men and 243 women were investigated. Analyses of participants' responses to a survey on stress showed significant differences between men and women on eight stress producers and on five coping strategies. PMID- 1763170 TI - Liking for chocolate, depression, and suicidal preoccupation. PMID- 1763171 TI - Accidental and unspecified deaths among prisoners as disguised suicides. AB - Analysis of 1987 data from the US Department of Justice for prisoners under the jurisdiction of state and federal correctional authorities indicated that suicide rates were not negatively correlated with accidental or unspecified death rates. These findings do not provide evidence of disguised suicides among prisoners. Possible explanations for high rates of unspecified death among prisoners are presented. PMID- 1763172 TI - Task-achievement, obsessive-compulsive, type A traits, and job satisfaction of professionals in public practice accounting. AB - This paper contains a description of the results of a two-year study of task achievement, obsessive-compulsive, Type A traits, and job satisfaction within randomly selected groups of 499 public practice accountants in Ontario, Canada. The results supported the notion that this profession attracts and conditions personalities with task-oriented, order-driven, Type A characteristics. With the exception of those who were advanced partners, the majority of public practice accountants were only moderately job-satisfied and were reportedly not committed to staying in their present jobs until retirement. PMID- 1763173 TI - On threat of shock as an elicitor of anxiety: a methodological note. AB - The effects of anxiety on the eyeblink component of the human startle response were measured in 32 college students. The manipulation of threat of shock was not successful in eliciting anxiety, suggesting that, while threat of shock can increase anxiety, this increase is not inevitable, illustrating the importance of a manipulation check of the effectiveness of the threat. PMID- 1763174 TI - Correlations between self-handicapping and self-defeating personality. AB - In this study scores on Strube's self-handicapping scale were correlated with scores on Schill's self-defeating personality scale. Berglas believes there are subtypes of self-defeating personality and that his concept of self-handicapping should be correlated with the three criteria which represent a self-protective component of self-defeating personality. Some support for Berglas' proposition was found, particularly for men. However, correlations with other components of self-defeating personality suggest the criteria thought to be self-protective may need to be reconsidered. PMID- 1763175 TI - Behavioral science in medical education: a 1987-1991 bibliography. AB - Holmes, et al. in 1988 compiled 61 studies in an updated bibliography of behavioral science in undergraduate and graduate medical education. Since then, 64 additional studies of behavioral science in medical education have been published and abstracted in Index Medicus and Psychological Abstracts, the sources for the bibliography. PMID- 1763176 TI - Finnish and American university students compared on a verbal aggression construct. AB - 232 Finnish and 145 American university students showed no significant differences on Infante and Wigley's measure of verbal aggressiveness. In keeping with general stereotypes, the men of both cultures (88 Finns, 86 Americans) were more verbally aggressive than were the women (144 Finns, 59 Americans). PMID- 1763177 TI - Role of craving for carbohydrates upon completion of a protein-sparing fast. AB - Pretreatment measures of craving for carbohydrates were related to higher dropout rates during the first month of a protein-sparing fast. 97 patients in a medically supervised weight-loss program, who were at least 50 pounds overweight, completed the Beck Depression Inventory, the Eating Inventory, and a questionnaire about their food habits before beginning a supplemented fast. While self-reported cravers of carbohydrates were significantly more likely to drop out during the first month of treatment than noncravers, this result does not appear to be related to differences in depression, disinhibition, or cognitive restraint. PMID- 1763178 TI - Personal Orientation Inventory correlated with physical health. AB - Predicting 92 subjects' physical health status from their scores on the Personal Orientation Inventory using regression analysis showed that those who obtained high self-regard scores and high self-actualizing value scores also reported better physical health. Those subjects who reported poorer physical health also scored high on the synergy scale. PMID- 1763179 TI - Nurses sue hospital for fraud re job security. PMID- 1763180 TI - Physicians retract opinion: nurses not negligent. Case in point: Galloway v. Baton Rouge General Hosp. (583 So. 2d 1169--LA (1991)). PMID- 1763181 TI - Pharmacological properties of the natural polyamines and their depletion by biosynthesis inhibitors as a therapeutic approach. PMID- 1763182 TI - Potassium channel openers: airway pharmacology and clinical possibilities in asthma. PMID- 1763183 TI - Antifungal chemotherapy--are we winning? PMID- 1763184 TI - The hopanoids, bacterial triterpenoids, and the biosynthesis of isoprenic units in prokaryotes. PMID- 1763185 TI - Isosterism and bioisosterism in drug design. PMID- 1763186 TI - Leukotriene antagonists and inhibitors of leukotriene biosynthesis as potential therapeutic agents. PMID- 1763187 TI - Bacterial resistance to antibiotics: the role of biofilms. AB - Bacteria adhere to natural and synthetic, medically important surfaces within an extracellular polymer generically termed the glycocalyx. This quasi-structure is a biofilm. The enhanced antibiotic resistance of biofilm bacteria, relative to floating (planktonic) bacteria, encourages the establishment of chronic bacterial infections. Resistance mechanisms include the hinderance of antibiotic diffusion by the glycocalyx, the physiology of the bacteria and the environment conditions of the niche in which the biofilm resides. PMID- 1763188 TI - Cholinergic systems in mammalian brain and spinal cord. PMID- 1763189 TI - Neurite growth from, and neuronal survival within, cultured explants of the nervous system: a critical review of morphometric and stereological methods, and suggestions for the future. PMID- 1763190 TI - 5-HT1A receptor responsivity in anxiety disorders and depression. AB - 1. Azapirones, selective partial agonists at the 5-HT1A receptor subtype, induce hypothermia and corticotropin (ACTH)/cortisol release as specific functional correlates of central 5-HT1A receptor activation. 2. Compared to controls, hypothermic and ACTH/cortisol responses to the azapirone ipsapirone are attenuated in patients with unipolar depression and panic disorder but not in patients with obsessive-compulsive disorder. The impaired thermic and neuroendocrine responses are associated with increased basal cortisol secretion in depressed patients but not in patients with panic disorder. 3. Chronic treatment with the selective 5-HT reuptake inhibitor fluoxetine decreases 5-HT1A receptor-mediated responses in patients with obsessive-compulsive disorder, while long-term treatment with the tricyclic antidepressant amitriptyline further decreases hypothermia following ipsapirone but has no effect on ACTH/cortisol release. 4. Alteration of the 5-HT1A receptor and/or its signal transduction pathways may play a role in the pathophysiology and treatment of anxiety disorders and depression. PMID- 1763191 TI - Animal study on the role of serotonin in depression. AB - 1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression. 2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse. PMID- 1763192 TI - Is a single tricyclic antidepressant trial an active treatment for psychotic depression? AB - 1. A retrospective chart review of 256 consecutively admitted depressed inpatients assessed their treatment response to optimal somatic therapy. 2. There were no differences in treatment response between patients with Major Depressive Episode (MD) and Major Depression with Psychosis (MD-P). 3. In addition, twenty six studies were reviewed to clarify the role of tricyclic antidepressants (TCA) in the treatment of MD-P. The authors conclude from this literature review that TCA's should not be considered an active treatment for MD-P patients. PMID- 1763193 TI - Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS). AB - 1. The pharmacokinetics of Dala1-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiency disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intravenous (i.v.) or intranasal (i.n.), via metered sprayer, administration. 2. The plasma kinetics appeared to be bi phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearance rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA. 3. Bioavailability, determined for a 2 mg test dose in six individuals was 9.3 +/- 6.9 nmol/L. Peak plasma levels of 41 +/- 30 nmol/L after 10 mg i.n., 2.8 +/- 5.9 nmol/L after 2 mg i.n., and 0.13 +/- 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months. PMID- 1763194 TI - Hypnotic action of flunitrazepam is reversed by proglumide in rats. AB - 1. Caerulein, an analogue of cholecystokinin (CCK-8), like CCK-8, has been shown to produce hypnotic effects similar to those of benzodiazepine (flunitrazepam). 2. Proglumide antagonizes the action of CCK-8 and of its analogue. 3. The aim of the present study was to demonstrate whether proglumide would affect the potent hypnotic action of flunitrazepam in rats. 4. The association of proglumide with flunitrazepam suppress the increase of total sleep time and slow wave sleep seen after flunitrazepam alone. Proglumide alone has no effect on sleep stages. The authors report here for the first time that the hypnotic action of flunitrazepam is antagonized by proglumide in rat. PMID- 1763195 TI - The effects of conditioning with amphetamine on the thermic effects of amphetamine and pentobarbital. AB - 1. Rats were injected with amphetamine (1.5 mg/kg) in the presence of a distinctive set of environmental stimuli (CS1) and saline in the presence of a different set of environmental stimuli (CS2) on different days for a total of 10 amphetamine and 20 saline injections. 2. The hyperthermic effect of amphetamine first increased but then declined to levels seen during the very first drug administration. 3. Following the conditioning phase, half the rats were injected with amphetamine in CS1 and half in CS2. Although there was little thermic effect of amphetamine injected in CS1, there was pronounced hyperthermia following amphetamine in CS2. 4. Next, pentobarbital (30 mg/kg) was administered to half the rats in CS1 and half in CS2. The hypothermic effect of pentobarbital was attenuated in CS2. PMID- 1763196 TI - Emerging pharmacology of nerve growth factor. AB - 1. Partial transection of the septo-hippocampal pathway decreased measures of presynaptic cholinergic function in the rat hippocampal formation. 2. Chronic intraventricular treatment with recombinant human nerve growth factor attenuated lesioned-induced deficits in cholinergic function. Following nerve growth factor treatment measures of choline acetyltransferase activity, acetylcholine synthesis and release were significantly increased compared to cytochrome c-treated lesioned animals. 3. Single injections of nerve growth factor were ineffective in altering lesioned-induced deficits in cholinergic function. 4. Chronic nerve growth factor treatment was ineffective in increasing presynaptic cholinergic function if administered 3 or more weeks following fimbrial transections. 5. The nerve growth factor-induced increases of presynaptic cholinergic function persisted for 3 weeks following the cessation of chronic 3 week nerve growth factor treatment. PMID- 1763197 TI - Antagonism of physostigmine induced hypothermia and neuroendocrine changes following exposure to different environmental temperatures. AB - 1. The magnitude of physostigmine-induced hypothermia increased with decreasing environmental temperature. 2. The hypothermic response was accompanied by significant changes in plasma levels of corticosterone, glucose and fatty acids. 3. Central cholinergic mediation appears to be a significant component of physostigmine-induced hypothermia and neuroendocrine changes at moderate temperature. 4. At lower ambient temperatures cholinergic blockers produced less antagonism of physostigmine-induced effects. 5. The decreased effectiveness of cholinergic blockers at low environmental temperatures and the increased plasma fatty acid levels under almost all conditions studied may be of importance in considering long term therapy with cholinergic agonists. PMID- 1763198 TI - Alpha-methyltryptophan as a therapeutic agent. AB - 1. Alpha-methyltryptophan, on administration to experimental animals gives rise to cerebral alpha-methylserotonin, which substitutes for serotonin in certain behavioral and functional tests. 2. Such results are consistent with the similarity of the properties of the two indoleamines with respect to storage, uptake and release, as well as with the 5HT2-receptor agonist activity of alpha methylserotonin. 3. It is proposed that alpha-methyltryptophan be regarded as a candidate drug for the provision of alpha-methylserotonin as a substitute for serotonin in disorders where the latter amine is thought to be deficient. PMID- 1763199 TI - Evolution of enzymatic regulation of prostaglandin action: novel connections to regulation of human sex and adrenal function, antibiotic synthesis and nitrogen fixation. AB - The recent determination of the amino acid sequences of enzymes that metabolize prostaglandins and steroids has revealed interesting connections between some of these enzymes. Human placental 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation of the C15 alcohol on prostaglandins E2 and F2 alpha, is homologous to 11 beta-hydroxysteroid, 17 beta-hydroxysteroid, and 3 alpha, 20 beta-hydroxysteroid dehydrogenases. That is, these four enzymes are derived from a common ancestor. Moreover, enzymes important in synthesis of antibiotics and proteins synthesized by soil bacteria that form nitrogen-fixing nodules in alfalfa and soybeans are homologous to 15-hydroxyprostaglandin dehydrogenase. These homologies provide important insights into the origins of intercellular communication that is mediated by prostaglandins, steroids, and fatty acids. PMID- 1763200 TI - The differences in 12-hydroxyeicosatetraenoic acid and thromboxane B2 release from guinea pig platelets. AB - Anti-12(S)-hydroxyeicosatetraenoic acid (12-HETE)-antibody and anti-thromboxane B2 (TXB2)-antibody were generated and applied to the radioimmunoassay. The detection limit for 12-HETE was 16 pg. The cross-reactivities of anti-12-HETE antibody were 4.6% for 15-HETE, 0.18% for 5-HETE and below 0.15% for leukotrienes and prostaglandins (PGs). 12-HETE and TXB2 released from guinea pig platelets were measured by radioimmunoassay. Platelet activating factor (PAF) at 10(-9) M induced the aggregation of platelets, the releases of immunoreactive-12-HETE (1.8 +/- 1.2 ng/10(8) platelets, mean +/- S.D.) and immunoreactive-TXB2 (18.5 +/- 17.3 ng/10(8) platelets). Collagen at 1 microgram/ml also evoked platelet aggregation, the releases of immunoreactive-12-HETE (2.7 +/- 1.1 ng/10(8) platelets) and immunoreactive-TXB2 (11.8 +/- 4.6 ng/10(8) platelets). By the stimulation with these compounds, TXB2 was produced in a greater amount than 12-HETE from guinea pig platelets. Although 10(-7) M and 10(-6) M U46619, a TXA2 mimetic, caused platelet aggregation, arachidonic acid metabolites were not released. These data suggest the presence of different mechanisms of platelet activation depending on each stimulus. PMID- 1763201 TI - Cicaprost inhibits metastases of animal tumors. AB - Since an involvement of platelet aggregation in the metastatic process has been found, platelet activation inhibitors were investigated for their potential to reduce tumor metastases. Recent in-vitro and in-vivo investigations showed an antimetastatic effect of prostacyclin (PGI2) and stable prostacyclin analogues. This study concentrates on the effect of the stable prostacyclin analogue Cicaprost (Schering AG) on tumor metastases in two metastasizing tumors of rodents. C57BL/6 mice bearing s.c.-implanted M5076 reticulum sarcoma were treated with Cicaprost in doses of 0.1-1.0 mg/kg throughout the experiment. Cicaprost in all doses tested reduced the number of liver metastases in a statistically significant manner. The 1.0 mg/kg dose, which decreases the median number of liver metastases to more than 93% compared to the control, was most effective. Cicaprost in the 0.5 mg/kg dose reduced the number of liver metastases in mice bearing i.v.-implanted M5076 reticulum sarcoma. In Cop-Fisher rats bearing s.c. implanted spontaneously metastasizing R3327 MAT Lu prostate carcinoma, Cicaprost in a dose of 1.0 mg/kg p.o. daily strongly reduced the number of lung metastases. These results indicate that Cicaprost is a potent inhibitor of tumor metastases in different tumor models in rodents. PMID- 1763202 TI - Pharmacological effects of oral E6123, a novel PAF antagonist, on biological changes induced by PAF inhalation in guinea pigs. AB - The effects of a newly synthesized PAF antagonist E6123, (S)-(+)-6-(2 chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2, 3,4,5- tetrahydro-8H pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine, on in vivo inhaled PAF-induced pulmonary changes were investigated. E6123 inhibited PAF inhalation-induced bronchoconstriction in guinea pigs with an ED50 value (p.o.) of 1.3 micrograms/kg which was lower than those of other PAF-antagonists such as WEB2347 (ED50 = 26 micrograms/kg) and Y-24180 (ED50 = 12 micrograms/kg). E6123 significantly inhibited PAF inhalation-induced eosinophil infiltration into the bronchiole and trachea, and bronchial hyperreactivity in guinea pigs after oral administration at 1 and 10 micrograms/kg, respectively. E6123 inhibited the PAF induced increase in intracellular free calcium ion concentration ([Ca2+]i) in guinea pig eosinophils with an IC50 value of 14 nM. The present results suggest that E6123 may be beneficial for the treatment of asthma, in which PAF is assumed to be involved. PMID- 1763203 TI - Interference in the radioimmunoassay of gastric prostaglandins by cimetidine, a histamine H2 blocker. AB - The present study was undertaken to assess whether cimetidine alters the levels of endogenous prostaglandin (PG) E2 and 6-keto-PGF1 alpha in the rat stomach. When cimetidine was mixed in vitro with a suspension of dextran-coated charcoal, to which [3H]-PGE2 had been adsorbed, levels of free [3H]-PGE2 were increased by cimetidine at concentrations above 1.0 mM, because of preferable adsorption of this blocker to the charcoal. Dextran-coated charcoal is used for the separation of antibody-bound [3H]-PGs from the free labelled compounds in the radioimmunoassay of PGs. Addition of cimetidine to standard solutions of PGE2 shifted the PGE2 calibration curve upward. Thus, when PGs in cimetidine containing samples were quantitated by reference to the normal calibration curve, the assessed levels of PG were lower than the actual levels. Removal of cimetidine from the assay samples was successfully achieved by use of SEP-PAK C18 columns. Rats were injected intraperitoneally with 100 mg/kg of cimetidine only once or with 20 mg/kg twice daily for 7 days. Using this cleaning method, we found that both the basal levels of PGE2 and 6-keto-PGF1 alpha and those levels increased by intragastric administration of 1.0 M NaCl solution did not differ between rats treated with cimetidine and those treated with vehicle. It can be, therefore, concluded that cimetidine does not affect the gastric PG production. PMID- 1763204 TI - Safety report. PMID- 1763206 TI - Remote area nursing: the silent reality. PMID- 1763205 TI - Unionism-professionalism: a false dichotomy. PMID- 1763207 TI - The Australian-American Nurses' Exchange: a unique experience in the celebration of nursing. PMID- 1763208 TI - [Correlation of plasma lipids and microproteinuria in diabetes mellitus]. AB - Microproteinuria is an early sign of clinical diabetic nephropathy, and it also has the power to predict cardiovascular mortality in both types of diabetes. In order to investigate this last aspect, we have analyzed serum lipids in diabetes type I and II (128 male patients) with or without microproteinuria [determined using MICRAL/TEST (Boerhinguer M)]. The results revealed the following: hypertriglycerinemia and a low HDL-Cholesterol level in insulin dependent diabetes mellitus together with hypercholesterolemia in non insulin dependent diabetes mellitus. It seems that both microproteinuria as well as hyperlipidemiain diabetes mellitus reflect a generalizes vascular lesion. PMID- 1763209 TI - [Idiopathic inflammatory myopathy. Analysis of 31 patients]. AB - A series of 31 patients suffering idiopathic inflammatory myopathy (IIM); we describe the extramuscular manifestations, specially pulmonary, the association to neoplasia, the histopathological characteristics, and their response to treatment. Fourty three percent of IIM patients presented a pulmonary involvement, 9% presented an associated neoplasia. The histopathological study allowed us to clearly differentiate dermatomyositis and polymyositis within IIM. 65% of patients initially responded to glucocorticoids and the most usefull therapeutic alternatives were azatioprine and cyclosporin-A. PMID- 1763210 TI - [Complications of liver transplant in intensive care. Experience in 130 cases]. AB - Liver transplant is the first therapeutic choice in most of the advanced liver diseases. Nevertheless, its performance originates a number of complications derived from: a) conservation techniques of the organ (in our study a prolonged time of hot ischemia was significantly associated with); b) surgery (all patients who required massive blood transfusions developed metabolic alkalosis); c) the graft itself (all the F 1. degrees were significantly infected), and d) extrahepatic causes (cyclosporin was responsible for high blood pressure and nephrotoxicity which appeared as oliguria with good response to furosemide, as well as hyperglycemia). Some other relevant results in our series were: right pleural effusion and thrombopenia which appeared with a high incidence. Infections were usually originated the staphylococcus which grows in half of the cultures. We also want to highlight the short mean stay and the low mortality incidence in the ICU. PMID- 1763211 TI - [Sneddon syndrome: diagnostic value of antiphospholipid antibodies]. AB - The association of livedo reticularis and cerebrovascular lesions is known as Sneddon's syndrome. It affects young adults and is more common in females. Repeated strokes lead these patients to residual deficits. Recently, Sneddon's syndrome has been described in a subset of patients with systemic lupus erythematous and primary antiphospholipid syndrome. We report two cases, one of them with antiphospholipid antibodies. Antiphospholipid antibodies do not seem to explain the events of Sneddon's Syndrome. Perhaps, different pathogenic mechanisms play role in the clinical expression of this syndrome. PMID- 1763212 TI - [Pericardial tamponade as a complication of T-cell cutaneous lymphoma]. AB - Mycosis fungoides is a T cell lymphoma characterized by the initial skin involvement. Organ infiltration generally occurs many years after the cutaneous presentation. The organ disease is accompanied of peripheral blood involvement (more than 20% lymphocytes have atypical convolute nucleus and there are palpable adenopathies. Pericardic involvement is a rare complication as the initial manifestation of the visceral disease, in patients with mycosis fungoides of long evolution. We present a patient suffering mycosis fungoide who presented a pericardic tamponade. The visceral disease in our patient was not accompanied by blood anomalies or palpable adenopathies. PMID- 1763213 TI - [Splenic abscess: clinico-microbiologic study of 15 cases]. AB - We have reviewed 15 cases of splenic abscesses diagnosed using a histopathological and microbiological study. Mean age was 48 years (range 18-78). Eight of them were male and 7 female. Eighty per cent of them had predisposing diseases, amongst which the most frequent were endocarditis and bacteriemia of other origin (26.6% in both cases). All patients presented fever and in 7 of them (47%) splenomegaly was appreciated. The most frequently isolated germs were gramnegative bacteria (33%), anaerobics (20%), and with a similar incidence grampositive bacteria, tuberculosis and fungii; in only one case cultures were sterile. Seven patients had multiple splenic abscesses and 8 patients single abscesses. Thorax x-ray showed alterations in more than half of the patients (53%). Abdominal echography was the diagnostic method in 67% of the patients and TAC in all the cases in which it was performed. Eight patients underwent splenectomy and one was surgically drained being the mortality rate of this group of 22%. Overall mortality was 33% and was related to the presence of multiple splenic abscesses (5/7, 71.4%), positive hemocultures (6/6, 100%), extrasplenic abscesses (7/8, 87.5%), and endocarditis (4/4, 100%), fungii infections (2/2, 100%), and late diagnosis (6/6, 100%). PMID- 1763214 TI - [What do general practitioners think about risk factors in arteriosclerosis?]. AB - At present the management of atherosclerosis is still based on the control of risk factors. The role of the general practitioner is very important in this setting and, therefore, we thought it would be useful to know the opinion on the subject of these physicians in our area. In order to find that out, we have polled by mail 286 physicians and have received an answer from 111. The largest number (91%) considered that the most frequent cause of death were cardiovascular diseases. In relation to coronary heart disease, hypercholesterolemia was considered to be the most important risk factor (65%), followed by arterial hypertension (14%). On the other hand arterial hypertension was considered to be the most important risk factor for cerebrovascular disease. There was agreement on low animal fat diet as the initial step in the management of the patient with hypercholesterolemia. Among the fats, olive oil is recommended more than other vegetable oils (64%). Fish was considered as an appropriate for these patients than blue fish, still persist. Seventy two per cent prescribe dietary treatment when total serum cholesterol levels are above 221 mg/dl. Eighty three per cent prescribe drug treatment when serum cholesterol levels are above 251 mg/dl. Fibrates are still the drugs mostly used with a low level of use of resins in our area. PMID- 1763215 TI - [New perspectives in the knowledge of endothelial mediators: their repercussion in clinical medicine. Fernandez-Cruz Lecture]. PMID- 1763216 TI - [Superior vena cava syndrome: radiologic study]. PMID- 1763217 TI - [Eosinophilia and giardia lamblia intestinal parasitism]. PMID- 1763218 TI - [Malignant melanoma of the lung. Apropos of a case]. PMID- 1763219 TI - [Subarachnoid hemorrhage as a manifestation of idiopathic thrombocytopenic purpura]. PMID- 1763220 TI - [Paralysis of the hypoglossal nerve secondary to venous catheterization]. PMID- 1763221 TI - [Disseminated candidiasis with pulmonary involvement]. PMID- 1763222 TI - [Primary Sjogren syndrome and IgA deficiency]. PMID- 1763223 TI - [Respiratory cryptosporidiosis: apropos of a new case]. PMID- 1763224 TI - [Subacute thyroiditis: an entity to be considered in the context of fever of unknown origin]. PMID- 1763225 TI - [Cervical actinomycosis in a carrier of human immunodeficiency virus]. PMID- 1763226 TI - [Hepatic epithelioid angiomatosis in the absence of HIV infection]. PMID- 1763227 TI - [Brain protection in heart surgery]. AB - We investigated the effect of CDP-choline on brain protection during extra corporeal circulation (ECC) in patients submitted to open-heart surgery. We studied forty patients, using neurological, neuropsychological, neuroradiological (CT scan), and CBF evaluations. All the patients were evaluated two weeks before (T1), two weeks (T2), one month (T3) and six months after surgery (T4). Patients were randomly divided into two groups: subjects of the first group were treated with 2000 mg/die e.v. from two weeks before surgery to ten days after surgery, and then with 1000 mg/die i.m., 15 days per month, for the following 6 months (Group A), while subjects of the second group were treated with 100 mg/die, from two weeks before surgery to six months after surgery (Group B). After surgery, neither neurological symptoms nor morphostructural lesions were observed in the two groups. However, in the Group A, 75% (15 out of 20) of the patients evidenced reduced performances on neuropsychological tests at T2, compared to T1. At T4 only 66% (10 out of 15) of the impaired patients showed a persistence of the deficit. In the Group B 70% (14 out of 20) of the patients displayed reduced performances at T2. At T4, almost all of the patients, namely 86% (12 out of 14), showed a persistence of neuropsychological deficits. CBF data showed hypoperfusion areas in 9 patients in Group A (1.7 +/- 4.15 mean areas per patient), and in 10 patients in Group B (3.33 +/- 1.3 mean areas per patient), at T2. In 2.2+ off PMID- 1763228 TI - [Prevalence of liver damage in alcoholics and drug addicts]. AB - The behaviour of drug addicts and alcoholics leads to the cooperation of risk factors concerning the development of chronic hepatitis, liver cirrhosis and hepatocarcinoma. The authors evaluate the prevalence of infections from B, C and Delta virus among a group of 40 intravenous drug users and 40 alcoholics affering to a territorial centre for drug dependence located in Valtellina (Italy). The prevalence of at least one serum marker of virus B, C or Delta hepatitis results to be 85% among drug addicts and 17% among alcoholics. The prevalence of Anti-HCV in alcoholics results to be much lower than found in former works. For what concerns the hepatitis B virus, 68% of the drug addicts and 10% of the alcoholics had at least one positive serum marker. The hepatitis B seronegative patients underwent vaccination with a recombinant-DNA vaccine. Those affected by chronic C hepatitis have been treated with alpha-recombinant interferon. All of the patients underwent health education, psychotherapy and drug-addiction therapy for a period of 8 months. These strategies in prevention and therapy aim to the reduction over the years of the incidence of chronic hepatitis liver cirrhosis and hepatocarcinoma among intravenous drug users and alcoholics. PMID- 1763229 TI - Purine nucleotide content of lymphocytes from healthy subjects and asymptomatic HIV-1 seropositive patients. AB - The purine nucleotide content of lymphocytes of normal subjects and asymptomatic HIV-1 seropositive patients was analyzed by HPLC. An increase in IMP and a decrease in ADP, GDP, ATP and GPT were observed in the HIV-infected patients with respect to healthy subjects. The changes may depend on different factors and indicate that the virus influences purine nucleotide metabolism of the cell. The finding sheds light on the metabolic situation of the infected cell, and could be applied to monitoring the disease. PMID- 1763230 TI - [Association of chronic obstructive bronchitis and upper digestive pathology. A clinical study]. AB - The association of chronic obstructive pulmonary disease (COPD) with esophageal gastric and duodenal disease is very common. In our experience 21.8% of patients with COPD were affected by peptic ulcer and 50.9% by inflammatory disease of upper digestive tract. This association appears independent from smoking and alcohol abuse. Dyspepsia and corticosteroid therapy were associated with endoscopic lesions (dyspepsia was present in 75.6% of patients with abnormal endoscopy vs 42.8% without endoscopic lesions, p less than 0.01 and corticosteroid therapy in 43.9% vs 0, p less than 0.001). On the contrary therapy with theophylline and beta 2-adrenoceptor-agonists is not associated with digestive disease. Spirometric parameters and blood gas analysis were not different among patients with and without endoscopic lesions. We suggest endoscopy of upper digestive tract in patients affected by COPD with dyspepsia and/or corticosteroid therapy. PMID- 1763231 TI - Pathologic sideroblastosis in myelodysplastic syndromes and acute nonlymphocytic leukemia. AB - To assess the incidence and the eventual prognostic relevance of pathologic sideroblastosis in myelodysplastic syndromes and acute nonlymphocytic leukemia, 5 acquired idiopathic sideroblastic anemias, 2 refractory anemias, 9 refractory anemias with excess of blasts, 10 acute nonlymphocytic leukemias were studied with regard to sideroblast type (ring or ferritin) and percentage. Pathologic sideroblastosis was commonly found in each subgroup, in some patients it appeared later in the course of the disease while in other reversed. In a successfully treated leukemic patient, pathologic sideroblastosis in otherwise normal bone marrow after therapeutic hypoplasia suggested clonal remission. Although the patient number was small, pathologic sideroblastosis seems to correlate with poor treatment response in leukemic patients. We conclude that systematic looking for pathologic sideroblastosis may have some biologic and clinical implications in myelodysplasia and acute leukemia. PMID- 1763232 TI - [Spontaneous remission of visceral metastases of hypernephroma after nephrectomy. Description of a case and review of pathogenetic hypotheses]. AB - We describe an absolutely spontaneous regression of visceral metastases from a renal carcinoma, following nephrectomy, in a 46 years old patient, who is at present in a complete uninterrupted remission for 39 months. After a literature review we point out the rarity of this event and emphasize its absolute spontaneity. Moreover, we suggest some considerations about the possible pathogenetic mechanisms of this unexpectedly positive outcome. Between these, because of the strongly positive psychologic attitude of the patient, the psycho neuro-immunologic one is suggestive. PMID- 1763233 TI - [Extraskeletal diffusion of multiple myeloma. A clinico-pathological description of 4 cases]. AB - The authors describe 4 cases of multiple myeloma that developed one or more extraskeletal localizations. They have evaluated the relation between the onset of the extraskeletal localizations and the following myeloma characteristics: tumor burden, clinical phase, chemotherapy response, prognostic significance. All the patients showed these localizations in a plateau phase of myeloma. None of the patients had fever, pancytopenia and in no one the performance status worsened. All patients obtained at least a partial reduction of the localization and only the patient with the retro-orbital localization, got worse and died for myeloma. The other three patients are alive and do not show any sign of progression. PMID- 1763234 TI - [Use of high-dose intravenous immunoglobulins in the therapy of connectivitis: preliminary experience in 5 cases]. AB - The Authors report their favourable experience concerning the treatment of five cases of connective tissue diseases with high-dose intravenous immunoglobulins: three cases of systemic lupus erythematosus with nephritis, hematological involvement and fever; one case of antiphospholipid antibody-associated pregnancy; and one case of juvenile dermatomyositis. Disease manifestations had proved refractory to previous conventional and sometimes aggressive therapies in all the patients. The results obtained are discussed on the basis of more recent data from the literature. Further investigation in the treatment of connective tissue diseases with intravenous immunoglobulins is suggested. However, this therapy should be employed only in carefully selected patients. PMID- 1763235 TI - [Anamnesis: a diagnostic passe-partout]. AB - There is universal consensus that the anamnesis is a fundamental and irreplaceable phase both for the formulation of the diagnosis and for establishing the correct physician-patient relation. In a high percentage of cases the diagnostic hypothesis formulated during the history-taking is successively confirmed. The analysis of the structure of the anamnesis has demonstrated to realize a cognitive approach of phenomenological type. This kind of approach fits with the structure of illness because of its dynamic aspect. That is the reason why it represents an indispensable diagnostic key. PMID- 1763236 TI - [History of immunologic deficiency]. AB - The description of agammaglobulinemia by O. Bruton in 1952 and later clinical studies by R. Good preceeded by sporadic clinical observations on deficits in the immune function associated with hyponutrition, nephrosis and tumors or with inborn errors of metabolism have all made their contribution to the emerging of the concept of immunological deficiency diseases. The clinical-pathogenetic description of immunological deficiency diseases has played a fundamental role in the understanding of the anatomo-functional bases of the immune system and research work on the phylogenetic and ontogenetic evolution of the immune response. Various methodologies, from the idea of experimentum naturae to molecular pathology, combine to define and direct this research, the result of an ongoing interaction between the hospital and the laboratory. This leads to a necessary theoretical-practical synthesis and contributes to the consolidation of an immunologically-directed medicine. PMID- 1763237 TI - [Physiopathological aspects of secondary hyperuricemia]. AB - Secondary hyperuricaemia expresses a heterogeneous group of clinical conditions generally classified according to the pathogenetic criteria. Hyperuricaemia can depend on an increased production, reduced renal excretion or on the combination of both. Myelo and lymphoproliferative diseases are clinically prevalent among the conditions accompanying this overproduction. The most frequent causes of reduced uric acid excretion are chronic renal failure and diuretic treatment. In recent years, several conditions of hyperuricaemia with mixed pathogenesis have revealed a common mechanism connected to the ATP cellular depletion. PMID- 1763238 TI - Guidelines for the evaluation of chemicals for carcinogenicity. Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment. AB - Chapter 1 gives some background information on general issues in chemical carcinogenesis. It briefly discusses mechanisms by which genotoxic and nongenotoxic substances may be involved in the development of cancer. The role of oncogenes and tumour-suppressor genes in molecular carcinogenesis is also described. The contribution from epidemiological studies to the overall assessment is dealt with in Chapter 2. The relative merits and limitations of different types of epidemiological investigations are discussed. Chapter 3 considers the major classes of chemical carcinogens with regard to the different mechanisms by which they exert their carcinogenic effects. The role of metabolism is considered. Chapter 4 covers the use of short-term predictive tests for screening for carcinogenic potential of chemicals (mutagenicity tests and cell transformation assays). Reference is made to the strategy for mutagenicity testing given in the Committee on Mutagenicity's 'Guidelines for the Testing of Chemicals for Mutagenicity', which is also relevant to predictive short-term testing for carcinogenicity. The main points to be considered in designing a carcinogenicity bioassay are covered in Chapter 5, and some of the problems which might be encountered during the performance of such a study are discussed. Special problems associated with the carcinogenicity testing of certain classes of substances are reviewed. The interpretation of the results of carcinogenicity studies is covered in Chapter 6. Statistical methodology is not dealt with in detail, but reference is made to more specialized guidelines. Advice is given on the problems of interpreting the biological significance of results. A number of factors which can influence the interpretation of the results of a study (confounding factors) are examined. Mechanisms of carcinogenicity are discussed in the context of interpreting the relevance to humans of a carcinogenic response in animals. Assessment of the hazards and risks from exposure to chemical carcinogens is discussed in Chapter 7. It explains the COC's differential handling of carcinogens, depending on whether or not a threshold level of exposure can be set for the chemical's carcinogenicity. It is proposed here and in earlier Chapters that threshold levels of exposure (below which there is no carcinogenic hazard) can reasonably be set for many non-genotoxic carcinogens if their modes of action are understood but not for genotoxic carcinogens (which are assumed to present a finite carcinogenic risk at any level of exposure). Methods of quantitative risk assessment of exposures to non-threshold (presumed genotoxic) carcinogens are briefly presented, and the COC's reasons for not using such methods are set out.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1763239 TI - A nursing model for chronic illness management based upon the Trajectory Framework. AB - The trajectory framework developed by Strauss and associates provides a conceptual basis for developing a nursing model that gives direction for practice, teaching, and research in the area of chronic illness. This paper presents an overview of the trajectory framework and shows how it can be used to generate such a nursing model. PMID- 1763240 TI - The trajectory of cancer recovery. AB - In response to the Corbin and Strauss illness trajectory framework, this paper offers a recovery model as a more relevant trajectory for cancer as a specific chronic disease and as a general framework for clinical science. As counterpoint, the course of recovery is considered as a separate but influential continuum vis a-vis the course of illness. The text presents an overview of the nature and meaning of cancer as a chronic disease, an operational definition of the recovery model, and a comparison and contrast of the illness and recovery trajectory frameworks in terms of their philosophic nature, therapeutic approach and research and educational and health policy-making emphases with regard to the cancer experience. When fully grounded in recovery science, the recovery trajectory model is predicted to be the more therapeutically effective clinical approach for professionals who care for patients diagnosed with cancer and their families. PMID- 1763241 TI - Using the Trajectory Framework: reconceptualizing cardiac illness. AB - Cardiac disease is known to be the leading cause of premature morbidity and mortality in the United States. Nursing management of cardiac illnesses, as such, is a primary concern for most practicing nurses. Dramatic changes in cardiac patient populations and associated technology available for treatment indicate a need to reconceptualize the nature of cardiac illness and to consider alternative approaches to guide the care of these patients. Traditional care, to a large degree, has focused upon acute illness, consequently limiting needed attention to the increasing group of patients suffering chronic illness and disability. In the present paper, the major changes in the cardiac patient population and in utilization of available technology are presented. The application of the Corbin and Strauss trajectory framework as an appropriate and useful framework for conceptualizing cardiac illness and care is then discussed. Five characteristics of the framework which render the model particularly well suited to address cardiac care are identified and discussed. These characteristics are: 1) comprehensiveness of care, 2) patient-centered care, 3) gender issues in care, 4) family-focused care, 5) technology and cardiac care. PMID- 1763242 TI - Applying the chronic illness Trajectory Model to HIV/AIDS. AB - The Corbin and Strauss chronic illness trajectory model is particularly helpful in explaining the different phases of HIV (Human Immunodeficiency Virus) disease, since this infectious process is characterized by both phases and subphases. The model is not particularly helpful in identifying when the illness trajectory begins, since the model starts with the onset of symptoms, and HIV disease is characterized by a long, symptomless phase. The importance of politics and economics is also underestimated when applying this model to HIV disease. While this model presupposes the existence of support systems as being significant others, HIV disease is unique in that whole family systems may be eliminated by this infectious process, i.e., the typical pattern of HIV disease in the 1990s is that of a father dying from AIDS, a mother sick with HIV disease, one or more siblings infected, and one or more siblings coping with tremendous losses at a very young age. PMID- 1763243 TI - Chronic mental illness: the timeless trajectory. AB - Mental illness encompasses many dimensions. While the etiology of most major disorders remains unclear, their devastating effects are readily apparent. The substantive and practical value of the trajectory model of chronic illness is examined in relation to the characteristics of major mental disorders. Two clinical vignettes illustrating the timeless trajectory of chronic mental illness are analyzed with reference to the model's components. The potential utility of this model for revitalizing research and practice in psychiatric-mental health nursing is discussed. PMID- 1763244 TI - Use of the Trajectory Model of nursing in multiple sclerosis. AB - Multiple sclerosis (MS) is a chronic, demyelinating disorder that is unpredictable in its overall course, in the type of symptoms that will predominate, and in its eventual outcome. It has been used as a model in research, education, and practice to examine the course of chronic illness, patient and family responses, coping and adjustment to chronic illness, and specific concepts and variables of interest to researchers. MS is used in this paper to evaluate for nursing practice the utility of the Corbin and Strauss trajectory model of nursing. The assumptions and major concepts of the trajectory framework are discussed, use of the model in multiple sclerosis is demonstrated, and the strengths and limitations of the framework as a nursing model are identified. PMID- 1763245 TI - Shaping the course of a marathon: using the Trajectory Framework for diabetes mellitus. AB - Persons with either insulin-dependent or non-insulin-dependent diabetes mellitus live with a chronic illness that can have both acute and long-term complications. The therapeutic regimen for glycemic control in diabetes is often complex and is lifelong; it requires special knowledge and skills for both patients and health care providers. In this article, the Corbin and Strauss trajectory framework for chronic illness management is clinically applied to the planning of patient care in two case studies of persons with diabetes. The benefits of using the trajectory framework as a model for care in diabetes include: introduction of the concepts of "locating" the patient on the trajectory and assessing the trajectory projection for both patient and provider, and a more realistic evaluation of incremental change in chronic illness. Two possible barriers to clinical application of the framework for diabetes management are: difficulty in translating the framework for clinical use, and some terminology in the framework that does not seem to describe reimbursable care. The trajectory framework provides a necessary shift in focus to quality of life issues in diabetes management over the lifespan. PMID- 1763246 TI - Factors associated with injury proneness. PMID- 1763247 TI - Can blood pressure be measured during exercise? A review. PMID- 1763248 TI - The induction and decay of heat acclimatisation in trained athletes. AB - Heat acclimatisation/acclimation involves a complex of adaptations which includes decreased heart rate, rectal temperature, perceived exertion as well as increased plasma volume and sweat rate. These adaptations serve to reduce physiological strain, improve an athlete's ability to exercise in a hot environment, and reduce the incidence of some forms of heat illness. Few differences exist in the ability of men and women to acclimatise to heat. Typically, older runners do not perform in the heat as well as younger runners, but physical training can negate differences between these groups. Hormonal adaptations (e.g. aldosterone, vasopressin) during heat acclimatisation encourage fluid-electrolyte retention and cardiovascular stability. Athletes with high maximal aerobic power (VO2max) acclimatise to heat faster (and lose adaptations slower when they are inactive in a cool environment) than athletes with low VO2max values. Physical training in a cool environment improves physiological responses to exercise at high ambient temperatures. In attempting to optimise heat acclimatisation, athletes should maintain fluid-electrolyte balance, exercise at intensities greater than 50% VO2max for 10 to 14 days, and avoid factors (e.g. sleep loss, infectious disease) which are known to reduce heat tolerance. Once acclimatisation has been achieved, inactivity results in a decay of favourable adaptations, after only a few days or weeks. PMID- 1763250 TI - Biomechanical factors associated with injury during landing in jump sports. AB - Many sport and movement activities contain a jumping component which necessitates landing. Several injury surveys across a variety of jump sports have identified the lower extremities and specifically the knee joint as being a primary injury site. Factors which might contribute to the frequency and severity of such injuries include stresses to which the body is subjected during performance (forces and torques), body position at landing, performance execution and landing surface. Most of the initial landing studies were primarily descriptive in nature with many of the more recent efforts being directed toward identifying the specific performance factors that could account for the observed system stresses. Continued investigations into landing are necessary to more thoroughly understand the force attenuation mechanisms and critical performance variables associated with lower extremity injuries. PMID- 1763249 TI - Protein intake and athletic performance. AB - For most of the current century, exercise/nutritional scientists have generally accepted the belief that exercise has little effect on protein/amino acid requirements. However, during the same time period many athletes (especially strength athletes) have routinely consumed diets high in protein. In recent years, the results of a number of investigations involving both strength and endurance athletes indicate that, in fact, exercise does increase protein/amino acid need. For endurance athletes, regular exercise may increase protein need by 50 to 100%. For strength athletes, the data are less clear; however, protein intakes in excess of sedentary needs may enhance muscle development. Despite these observations increased protein intake may not improve athletic performance because many athletes routinely consume 150 to 200% of sedentary protein requirements. Assuming total energy intake is sufficient to cover the high expenditures caused by daily training, a diet containing 12 to 15% of its energy from protein should be adequate for both types of athletes. PMID- 1763251 TI - Rehabilitation concerns following anterior cruciate ligament reconstruction. AB - Rehabilitation following anterior cruciate ligament reconstruction is a subject of controversy in the orthopaedic and rehabilitation literature. With an increasing number of these operations currently being performed and with the advent of arthroscopically assisted ACL reconstruction over the past several years, particular rehabilitation needs and problems have been identified in association with these patients. Various authors have stressed one or a combination of a few basic themes which outline the basic rehabilitation concerns following ACL reconstruction. The most fundamental concern is the need to initiate motion very soon after surgery. Prolonged postoperative immobilisation is known to cause serious complications after ACL reconstruction which can be avoided by early motion. Positions or activities which may apply excessive stress to a newly reconstructed ACL must also be considered. The amount of protection required by the graft will vary depending upon the type of graft used and the quality of fixation obtained intraoperatively. Most authors agree that nonweightbearing, active resistive quadriceps exercises should be avoided for an extended period, while closed chain exercises may be initiated much earlier. Strength recovery is obviously important for the quadriceps postoperatively, but maximal strength returns of all of the muscles about the knee must be pursued. Hamstring strength is of particular concern as this may provide an active support to the reconstructed ACL. Sensory loss in the knee after ACL disruption should also be addressed during rehabilitation, prior to a patient's return to full athletic activity. Progressive neuromuscular re-education exercises which rely on sensory input from intact pericapsular structures are encouraged. A final concern is the role of bracing after ACL reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763252 TI - Laser-evoked cerebral potentials in the assessment of cutaneous pain sensitivity in normal subjects and patients. AB - Heat stimuli, applied to the skin by non-contact radiation pulses emitted by a CO2-laser, activate simultaneously both A-delta (mean conduction velocity 14 m/s) and C-fibres (0.8 m/s), which terminate in the most superficial skin layers. Correspondingly, brief heat stimuli elicit two pain sensations with mean reaction times of about 500 ms and 1400 ms. Similarly, two evoked potential waveforms were observed in the electroencephalogram: the late components N240/P370 and the ultralate components N1050/P1250. The shape of the two components was reproducible in independent samples of healthy volunteers. In patients with dissociated sensory loss, the laser evoked cerebral potentials are affected, depending on the kind of disturbed nerve and tracts. This is shown in patients with syringomyelia, encephalomyelitis disseminata, myelitis, Brown-Sequard syndrome, Wallenberg syndrome. In cases with hereditary motor and sensory neuropathy type I or with neurosyphilis, ultralate potentials are observed as correlates of delayed pain perception in the affected body areas. The laser evoked cerebral potentials reflected the clinical disorder of pain sensitivity in most cases, whereas somatosensory evoked potentials in response to conventional nerve stimuli failed in objectifying the diagnosis. As such, evoked cerebral potentials in response to laser heat stimuli applied to the hairy skin can be used for an overall examination of the functional integrity of peripheral small fibres, anterolateral tracts and thalamocortical projections. PMID- 1763253 TI - [Genetics of neurofibromatosis: recent progress and prospects]. AB - Two forms of neurofibromatosis are currently described. Von Reckinghausen Neurofibromatosis (NF 1) is the classic and common form, recently localised to chromosome 17. Neurofibromatosis type 2 (NF 2) or bilateral acoustic Neurofibromatosis, formerly the "central form" of von Reckinghausen disease, is characterized by multiple brain tumors, most often bilateral acoustic neuromas. The NF 2 mutation lies on the long arm of chromosome 22. The two forms predispose to benign or malignant familial tumors, derived from neural crest germ lines, such as Schwann cells. Rapid progress in the understanding of mechanisms underlying neurological tumor formation is expected in these inherited diseases. Molecular biology will allow the precise identification of genes responsible for the neurofibromatose syndromes. Practical applications, such as screening of individuals at risk for the disease will soon be available. Medical follow-up and genetic counselling should improve as a result of these advances. PMID- 1763254 TI - [Spontaneous intracerebral hemorrhages in young patients. Study of 33 cases]. AB - We report 33 cases of intracerebral hemorrhage (ICH) in patients aged from to 9/44 years (male: 20, female: 13, mean age: 32.5 years). ICH was due to vascular malformations in 39 p. 100 of cases, to arterial hypertension in 30% and to various causes in 18% no cause could be found in 13% of the cases. ICH was lobar in 64%, deep in 33% and infratentorial in 3% of the cases. The diagnosis was assessed by arteriography in 9 patients. The vascular malformations were arterial angiomas, saccular aneurysms and cavernous angiomas. Death rate was 24%. There was a fast ICH handicap in 40% of cases. Only 36% of the patients were not disabled. PMID- 1763255 TI - [Prolonged traumatic coma caused by diffuse axonal lesions]. AB - A 22-year old male patient was admitted for deep coma probably of traumatic origin. There was neither fracture of the skull nor expansive intracranial lesion. The patient survived for 6 years and 8 months without any change in consciousness. Post-mortem neuropathological examination showed lesions which predominated in the white matter and had features that were compatible with diffuse axonal injury. The mechanism responsible for these lesions seems to be stretching and shearing of axones at the moment of impact. The exceptionally long duration of survival probably accounts for the severity of the lesions observed. PMID- 1763256 TI - [Sensory neuropathy and subacute dysautonomia. Clinical and pathological study]. AB - We report a case of severe subacute autonomic and sensory neuropathy in a 52 year old man. Cerebrospinal fluid protein was 275 mg/dl. Electrophysiological data were consistent with an axonal sensory neuropathy. Nerve biopsy showed a severe decrease in myelinated fibers, and a less severe loss of unmyelinated fibers. No cause was found and recovery was almost complete over 4 years, with minimal persistent dysautonomia. This case and 4 similar reported cases are compared with pure dysautonomia and with sensorimotor dysautonomic neuropathy. The site of damage is discussed and it is suggested that these cases are axonal forms of inflammatory polyneuropathy. PMID- 1763257 TI - [Left pseudothalamic cortical syndrome and pain asymbolia]. AB - We report a case of left pseudothalamic cortical syndrome associated with asymbolia for pain in a right-handed male patient. The responsible lesion, detected at both CT and MRI, was infarction of the superficial territory of the middle cerebral artery, restricted to the posterior insula, the superior aspect of T1, the parietal operculum and the supramarginal gyrus. The ascending parietal gyrus and the thalamus were spared. This case, together with data from the literature, suggest that the somatosensory area II was responsible for the pseudothalamic syndrome. This interpretation is concordant with the hypothesis that S II plays the principal role in passive somatosensory discrimination, whereas S I plays the principal role in active discrimination implying stimulus exploration. The location of lesions that were responsible for asymbolia for pain is discussed. This case and those reported by Berthier et al. (1988), provide arguments in favour of Geschwind's hypothesis which attributes asymbolia for pain to sensory-limbic disconnection due to damage of the insula. PMID- 1763258 TI - [Ataxic hemiparesis and simultaneous supra- and subtentorial hematomas]. AB - In a chronically hypertensive woman with a rapidly developing right ataxic hemiparesis syndrome, computed tomography and magnetic resonance imaging (MRI) revealed two small unrelated hemorrhages: one in the posterior limb of the left internal capsule, the other in the right cerebellar hemisphere. In this patient, the ataxic hemiparesis syndrome might have resulted either from the association of the two lesions or from the capsular hemorrhage alone. The rarity of simultaneous hypertensive hematomas and the value of MRI in the diagnosis are underlined. PMID- 1763259 TI - [Opsoclonus associated with multisystemic sarcoidosis]. AB - A 32 year old patient with unexplained cough developed an opsoclonus-ataxic myoclonic syndrome. Chest X-ray film were normal at this onset but became pathologic, and the diagnosis of multisystemic sarcoidosis was made. The possibility of sarcoidosis being the cause of the opsoclonus is discussed. PMID- 1763260 TI - [Nuclear oculomotor nerve syndrome and ocular tilt reaction caused by mesencephalic hematoma]. AB - A 78-year-old man had a midbrain hemorrhage, documented by CT scan and MRI, resulting in a mild cerebellar syndrome predominant on the left upper limb, lateropulsion, and a complex ocular motor syndrome. The latter was associated with right nuclear oculomotor nerve palsy, gaze paresis to the left for voluntary saccades, and a tonic ocular tilt reaction. Pathophysiological mechanisms are discussed. PMID- 1763261 TI - [Axonal polyneuropathy in Chagas disease]. AB - We report the case of a 44-year-old woman presenting with chronic symmetrical, sensitive polyneuropathy on the lower limbs in the course of Chagas' disease. The electrophysiological findings were in keeping with axonal degeneration. The histological data displayed axonal degeneration with perivascular inflammatory mononuclear cells in the epineurium, with some neutrophils and eosinophils. Mononuclear cells surrounding endoneurial vessels were observed. Laboratory data did not suggest neither a mixed connective tissue disease nor a collagen vascular disorder. Hematological disease, malignancies, drug-or medicine-induced neuropathy were ruled out. The polyneuropathy in this case was probably related to Trypanosoma cruzi infection on account of the presence of high levels of anti T. cruzi antibodies, and an immune mechanism might play a role in the vasculitic process. PMID- 1763262 TI - [Acute corticosteroid myopathy in patient with asthma]. AB - A patient, treated by mechanical ventilation with pancuronium or atracurium and with intravenously administered corticosteroid for status asthmaticus, presented with rhabdomyolysis (severe amyotrophy and marked of creatine kinase activity) and acute flacid and areflexic quadriplegia, involving the proximal and distal muscles but sparing the cephalic musculature. After review of the investigations (biochemistry, electromyogram, muscle biopsy), the diagnostic of acute corticosteroid myopathy following status asthmaticus was suggested, and a pancuronium neuromuscular complication or a critically ill polyneuropathy excluded. The non-inflammatory rhabdomyolysis concerned all the fiber types. Predominantly distal weakness resolved six months after the insult, in spite of the laboratory recurrence of the rhabdomyolysis at the time of a new status asthmaticus briefly treated with corticosteroid. PMID- 1763263 TI - [The corpus luteum and progesterone secretion]. AB - The pulsatility of LH secretion has been known only since 1970. The pulsatility of progesterone secretion has now also been shown. The frequency and amplitude of these pulses vary during the three phases of the luteal period. The first or early luteal (EL) phase lasts four days starting from the peak of LH. There is no pulsatility of progesterone during EL. The frequency of LH pulsatility is 103 +/- 8 minutes. The second or mid luteal (ML) phases, from +6 to +9 days after the peak of LH, is characterised by pulses of LH and of progesterone, most often in positive crossover correlation and with 7 to 14 pulses per 24 hours. The frequency of LH pulsatility is 166 +/- 33 minutes according to Filicori. The amplitude of LH secretion is 4 to 40 ng/ml. The third or late luteal (LL) phase, occurring at +11 days before the menstrual period, has the same characteristics in terms of quality but shows variations in frequency and amplitude towards a decrease. Thus the amplitude of progesterone secretion is 2.8 to 9 ng/ml (Veldhuis). In the opinion of clinicians, the corpus luteum is independent up to LH+ 5 days. The injection of hCG during this time is ineffective. A single progesterone level is sufficient if the result is 10 ng/ml or more. The problem remains complex concerning results below 10 ng/ml. The solution suggested for the present is that described by Olive: during ML and/or LL, three samples in the morning at hourly intervals and two endometrial biopsies during two consecutive cycles. PMID- 1763264 TI - [The value of endometrial biopsy in the assessment of the corpus luteum]. PMID- 1763265 TI - [The role of umbilical Doppler in the monitoring of pregnancy]. AB - Doppler recordings from the umbilical cord in utero explores the placental reserves and fetal well being. Compliance with the technical conditions of performance ensures reliability of the determination. This examination predicts the state of the child at birth, particularly in cases of delayed intra-uterine growth, maternal hypertension or gestosis, and in cases of twin pregnancies. The change is maximum when the umbilical diastolic flow disappears. In the absence of any pathological context, a congenital or chromosomal abnormality should be considered and the fetal karyotype should be determined. Follow-up is carried out during hospitalization, and the decision on whether to extract the fetus is based on cerebral Doppler recordings and a detailed analysis of the fetal heartbeat. PMID- 1763266 TI - [The role and limits of Doppler studies of the uterine arteries]. AB - Doppler study of the uterine arteries investigates the utero-placental vascular bed. It can be used to identify a population at risk of vascular complications, in particular retroplacental hematoma. This type of study is indicated when there is a history of a vascular problem during pregnancy, as well as following the onset during pregnancy of hypertension, pre-eclampsia, delayed intrauterine growth or thrombocytopenia. The measurement technique avoids neighbouring vessels. An abdominal or vaginal approach may be used. The quality of the signal recorded and compliance with practical technical aspects enable long term prediction of the course of the pregnancy and the organisation of appropriate obstetric monitoring. PMID- 1763267 TI - [Utero-placental circulation]. PMID- 1763268 TI - [Distribution of the concentrations of angiotensin II (A II), A II receptors, hPL, prolactin, and steroids in human fetal membranes]. AB - By analyzing human trophoblastic tissues at the full term of pregnancy, this study shows the highest levels of angiotensin-II (729 +/- 111 and 602 +/- 105 pg/g of tissue), angiotensin-II receptors (295 +/- 30 and 250 +/- 32 fmol/mg proteins), human placental lactogen (973 +/- 154 and 680 +/- 28 micrograms/g) and progesterone (1,501 +/- 193 and 1,070 +/- 151 ng/g) in chorionic villi and in placental basal plate respectively. Tissue values of angiotensin-II, hPL and Progesterone were 4 times superior to those obtained in amniotic fluid and in umbilical and maternal blood. Estradiol values in chorionic villi were similar to those in placental basal plate, in chorionic plate and in chorion, but significantly higher (p less than 0,001) than in amnion, amniotic fluid and in umbilical and maternal blood. The concentrations of prolactin in chorion were 3 times superior than those found in amnion, in placental tissue, in amniotic fluid and in umbilical and maternal blood. A positive correlation was observed between Angiotensin-II and its receptors and also with hPL, P4/hPL ratio and E2/P4 ratio. Thus, angiotensin-II could play an important role in the physiology of pregnancy, due to its vasopressive action and due to its interactions with other peptides and chorio-placental steroids. PMID- 1763269 TI - [Von Recklinghausen's disease and pregnancy]. AB - On the basis of six cases and a review of the literature, the authors identify the special features associated with the combination of von Recklinghausen's disease and pregnancy. Fertility is unaffected and pregnancy possible. Careful monitoring is required because of severe complications. In certain probably minor forms of the disease, the outcome of pregnancy is favourable with no complications. PMID- 1763270 TI - [Multiple pregnancies. Neonatal morbidity and mortality]. AB - The increase in the number of multiple pregnancies and the high incidence of prematurity in this type of pregnancy justifies a pediatric evaluation. A retrospective study (1985-1989) compared the perinatal and neonatal characteristics of children resulting from 14 multifetal (at least 3 fetuses) pregnancies, with a gestational age of less than 34 weeks, with 27 children resulting from monofetal pregnancies of the same duration. Neonatal morbidity and mortality appeared to be similar in both groups. Thus at this very early time of onset of labour (mean gestational age of 30 weeks), fetal multiplicity expressed itself neither by any particular neonatal pathology nor by malnutrition. PMID- 1763271 TI - [Classic complication of uterine revision after a late abortion: uterine synechia. Current review based on two cases]. AB - The authors use two personal cases to review the etiological circumstances, pathology and clinical and paraclinical manifestations, stressing in particular the current value of diagnostic and therapeutic hysteroscopy. Advice is given concerning prevention and treatment. PMID- 1763272 TI - [Uterine rupture due to unrecognized uterine scarring]. AB - Uterine rupture affecting the pregnant uterus has become rare. It occurs essentially in the presence of scarring. The cases reported here described rupture following evacuation curettage which had caused an unrecognized uterine perforation. While such perforations often have no serious consequences, this explaining the usual abstention from treatment, it is nevertheless important that acute complications (intestinal or vascular trauma) or long term (uterine rupture of pregnant uterus) should not pass unrecognized. PMID- 1763273 TI - [A twin pregnancy in a bicornuate uterus]. AB - A case of twin pregnancy in bicornuate uterus with a fetus in each horn is presented. During the second trimester, the rudimentary horn ruptured. This horn was extirpated and two non viable fetus were delivered by cesarean section. Later on, the patient had another pregnancy in the unicornuate uterus. She was delivered at 36th week of pregnancy by cesarean section. The baby was in good condition. PMID- 1763274 TI - The varied uses of gallstones. PMID- 1763275 TI - The language of epidemiology (VI): prevalence. PMID- 1763276 TI - The natural and unnatural history of gallstones. PMID- 1763277 TI - Assisted reproductive technics for the treatment of male factor infertility. AB - Several treatment choices remain for the couple with male factor infertility due to idiopathic male infertility or in couples in which specific therapy has failed. Empiric medical therapy continues as a viable option; however, the physician and patient must understand that the success rates with any of the pharmacological therapies remain suboptimal. In addition, this therapy should only be used for patients with idiopathic male infertility. It is not indicated for other classes of infertile males. Another option is that of IVF and related technologies. These technics continue to improve and we can expect more specific technics to be developed to optimize fertilization and pregnancy rates in those couples with male factor infertility. At the present time, the pregnancy rates achieved with this technology in male factor couples are less than those in non male factor patients. In addition, all of these technics entail considerable expense, often not covered by insurance. The third alternative for the patient with idiopathic male infertility is that of therapeutic insemination with the husband's sperm. Recent studies combining ovarian hyperstimulation with IUI suggest a clear advantage of this technic over other insemination approaches. As this treatment is significantly less expensive and time-consuming than the prior therapies, it should be considered when choosing therapy. Additional choices the couple with male factor infertility should consider are adoption and therapeutic donor insemination. It is only after careful consideration of all the available options that an appropriate decision can be made. This will vary, depending on the particular clinical characteristics of the couple as well as their social and financial situation. PMID- 1763278 TI - Hospitalizations for biliary tract disease, 1990. PMID- 1763279 TI - Doctors, drug companies and gifts. AB - This paper by Chren and Landefeld was originally presented at the Miriam Hospital on March 21, 1991, as the 1991 Lichtman Oration, an annual meeting devoted to ethical problems in medicine honoring Herbert C. Lichtman, MD, former physician in-chief at the hospital. Because of the importance of this paper, and its controversial character, the Journal has asked a number of practicing physicians and other concerned persons to offer their opinions on this paper. These commentaries will then be published in a subsequent issue of the Journal, along with reactions by our readers. PMID- 1763280 TI - Light and transmission-electron microscopy study of enamel organ cells in germectomized human third mandibular molars. AB - Using nine serially sectioned germectomized mandibular third molars it was possible to examine light microscopical (LM) and transmission-electron microscopical (TEM) features of maturing human enamel organ cells. The degree of enamel mineralization was estimated by quantitative imbibition studies in polarized light. It was possible to distinguish between three progressive stages of enamel mineralization. The most advanced stage was characterized by external enamel porosity. In the least advanced stages the enamel porosity appeared more extensive beneath a less porous surface layer. Ruffle- and smooth-ended ameloblasts were identified corresponding to the maturing enamel. Smooth-ended ameloblasts were the most frequently observed. However, no preferences for one of the two cell types could be observed in relation to the different stages of enamel mineralization. The maturing human enamel organ cells broadly revealed the same characteristics with respect to morphology features, intracellular organization, and junctional complexes as described in the maturation zone of the rat incisor enamel organ. Our findings therefore add to the view that the basic pattern of amelogenesis is identical in human and rat incisor enamel. PMID- 1763281 TI - Experimental erosion of dentin. AB - Experimental erosion in human dentin was investigated with scanning electron microscopy. Erosion was caused by solutions containing either 0.030 mekV/g malic acid (pH 3.4), 0.034 mekV/g phosphoric acid (pH 2.6), or 0.038 mekV/g citric acid (pH 2.8). Test specimens prepared from the coronal parts of erupted third molars were immersed in the solutions from 30 s to 60 min. When compared with controls, exposure of dentin tubules was observed in all the specimens already after 30 s immersion, irrespective of the acid used. Mineral loss was seen to progress at the interface between peritubular and intertubular dentin in specimens immersed for 60 s in the acidic solutions. Longer times of immersion resulted in hollowing of the tubular openings by complete destruction of the peritubular dentin. Surface roughness and porosities were seen also at the intertubular areas. Although based on a simplified study model, our results may explain why so many patients with erosions suffer from painful sensitivity of their teeth: the acids causing erosion can expose inner dentin structures to outer stimuli by significant enlargement of the dentinal tubules. PMID- 1763282 TI - Irradiation of human dental tissues with CO2-, Nd:YAG-, and CO2-Nd:YAG combination laser. AB - Extracted third molars were used to study the effect of Nd:YAG laser irradiation combined with CO2 laser beam on dental hard tissues. The specimens were studied with SEM after lasing and the size of the impact areas and beam penetration into enamel and dentin were planimetrically analyzed. High-energy CO2 laser (e.g. 10 s irradiation with 10 W output energy) penetrated all enamel and dentin. The simultaneous addition of Nd:YAG irradiation to the CO2 beam was found to increase the effect of CO2 laser, while Nd:YAG irradiation alone, used with equivalent energy densities, did not cause any effect on enamel surface. Thus, Nd:YAG laser was found to potentiate statistically significantly the effect of CO2 irradiation, but the morphologic alterations on dental hard tissues, such as crater formation at the beam focus site, appeared to be due to CO2 irradiation alone. PMID- 1763283 TI - Concepts of health and disease and caries prediction: a literature review. AB - Biomedical determinants of dental caries have been more extensively investigated than psychosocial factors and their impact on caries prevalence and incidence seems to be greater. However, a majority of these investigations relate to children and adolescents. An implementation of social and psychologic variables may be more relevant regarding dental caries in adults. In addition, a multidisciplinary approach might improve our understanding of dental caries as a multifactorial disease and bridge the gap between a biomedical concept and a more holistic approach to dental health. PMID- 1763284 TI - Effect of whole saliva on the rheologic behavior of extracellular water-soluble glucan produced by Streptococcus mutans. AB - The viscosity of mixtures of Streptococcus mutans water-soluble glucan and stimulated whole saliva or buffer was measured at pH 5, 6, 7, and 8. The viscosity was measured as a function of shear rate in the range 15 s-1-230 s-1. Though the centrifuged saliva had a viscosity close to that of water it increased the viscosity of the glucan up to 65% at pH 6 and 55% at pH 7 and at a shear rate of 20 s-1, indicating an interaction between saliva components and glucan that could be an important part of the cohesive forces of plaque matrix. The interaction between saliva and glucan was less pronounced at pH 5 and 8, which indicates a charge-dependent interaction. The viscosity increase at pH 6 and 7 was higher at low than at high shear rates, suggesting a higher contribution to plaque stability when weak as opposed to high mechanical forces are exerted on the plaque. PMID- 1763285 TI - Oral implantation in man of Streptococcus mutans in relation to salivary IgA activity. AB - Oral implantations of and salivary IgA activity against a freshly isolated Streptococcus mutans strain and a repeatedly subcultured variant strain were studied in 20 subjects. The variant strain was eliminated at a higher rate than the parent strain. Both strains were eliminated at a lower rate in subjects with high oral levels of indigenous mutans streptococci than in subjects with low levels of these microorganisms. Subjects with high respectively low IgA activity against the parent strain also had high respectively low IgA activity against the variant strain (P less than 0.01). The correlation between IgA activity and clearance rate of implanted bacteria was not statistically significant. However, following both implantations, median values of IgA activity were consistently higher in subjects who had eliminated the implanted strain than in subjects who had not. PMID- 1763286 TI - Interactions between and within Streptococcus mutans and Streptococcus sobrinus isolated from humans harboring both species. AB - The prevalence of Streptococcus mutans and Streptococcus sobrinus was examined in plaque samples from small discrete areas of the buccal tooth surfaces of seven subjects. Strains of S. mutans and S. sobrinus were isolated and tested for bacteriocin-mediated interactions between and within the two species, using the stab inoculation technique. S. mutans and S. sobrinus did not colonize each tooth surface uniformly and, in plaque from small discrete sites, S. mutans and S. sobrinus were either undetected or present in different interspecies proportions. Within the same subject, there were no bacteriocin-mediated interactions between strains of the same mutans species and no difference in bacteriocin activity was found between the strains of S. mutans and S. sobrinus from different sites. When bacteriocin interactions were tested between isolated strains from all seven subjects a somewhat higher inhibition ability was found for producer strains isolated from plaque compared with those isolated from saliva. S. mutans appeared to be more bacteriocinogenic than S. sobrinus. Replacing the glucose in the medium with sucrose enhanced the bacteriocin activity of S. mutans towards other S. mutans strains but reduced the inhibitory interaction towards strains of S. sobrinus. PMID- 1763287 TI - Effect of repeated sampling and prestimulation on saliva buffer capacity and flow rate values in children. AB - Great variations reported in the frequency distribution of buffer capacity values may partly be due to methodological differences in saliva sampling. In this study we wanted to see to what extent these variations are due to repetition and prestimulation. 9-yr-old schoolchildren (n: 41, 23 girls and 18 boys), who had never had saliva samples taken before, participated in the present study. The repetition tests were carried out between 9 and 11 a.m. on three subsequent days. The effect of prestimulation was tested 4 days later with the same subjects. The buffer capacity of the samples was determined electrometrically immediately after sampling using the commercial Dentobuff-test. The intraindividual analysis revealed a significant increase in flow rate but not in buffer capacity along with repetition of the sampling. The analysis further showed that the buffer capacity of children accustomed to saliva sampling increased significantly through prestimulation of 1 min. The use of prestimulation resulted in substantial changes also in the frequency distribution of the buffer capacity values. Our results emphasize the importance of proper sampling conditions in saliva collection when screening children for high caries risk. PMID- 1763288 TI - Conceptions of dental amalgam and oral health aspects during pregnancy in Finnish women. AB - All 277 pregnant women (mean age 28.4 yr, SD 4.6) living at the Lohja municipal health center area in Southern Finland participated in a survey during the first 6 months in 1990. The women's own opinions of the effect of pregnancy on their oral health were questioned during their first trimester of gestation. A special emphasis was put on the attitudes of dental restorative materials. The results showed that 57% of the subjects would have accepted the use of any restorative material during pregnancy while 43% were against one or more materials. 77 (65%) were opposing dental amalgam. 129 women (47%) were of the opinion that pregnancy as such is detrimental to their dental health. This opinion was significantly more frequent among women who were pregnant for third or more times than those having their first gestation. 70 (26%) thought dental treatment to have an effect on their gestation. Also 70 subjects (26%) thought that dental treatment may affect normal development of the fetus. The results showed that in spite of the long tradition in maternity counseling in Finland, the conceptions among pregnant women are often erroneous from the dental point of view. PMID- 1763289 TI - Fracture toughness measurements of some dental core ceramics: a methodologic study. AB - Fracture toughness is regarded as an important property of dental ceramics. The most widely used methods for fracture toughness (KIc) determination are based on assessment of cracks created by hardness indentations. Different formulas have been developed for KIc calculations and all these methods and formulas include empirical factors based on pure ceramics, i.e. non-composite ceramics. These factors may, however, vary for a specified method for materials with different and complex structure. An important question is whether the various proposed methods and formulas lead to approximately the same numerical KIc values or at least to the same ranking of materials. The aim of this work was to compare two indentation methods and various formulas for calculation of KIc values when used on four commercial composite dental ceramics. The two applied methods and the different formulas showed substantial differences in the obtained values for one and the same material and a different ranking of various materials. It is unknown which method gives the most correct KIc values for these ceramic materials. PMID- 1763290 TI - In vitro antibacterial effect of chlorhexidine added to glass-ionomer cements. AB - The aims of the present study were to investigate the antibacterial properties of glass-ionomer cements containing different concentrations of chlorhexidine and the possible release of chlorhexidine from the compound. Chlorhexidine gluconate or diacetate was mixed with glass-ionomer cements and tested in vitro against strains of Lactobacillus casei and mutans streptococci. A spectrophotometric test was used to monitor the release of chlorhexidine from the mixture. In a broth culture test, the higher the concentrations of chlorhexidine in the mixture, the longer the time of antibacterial effect on Streptococcus mutans and the greater the tendency of the material to deteriorate. Agar diffusion tests revealed bacterial inhibition in a dose-response manner. The tested bacterial strains were similarly inhibited and the antibacterial properties decreased with time. A minor portion of added chlorhexidine was released from the cement. The deterioration of the cements indicates that the material could be useful as a varnish-like chlorhexidine carrier. PMID- 1763291 TI - The eosinophil in inflammatory bowel disease. PMID- 1763292 TI - Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. The Danish Budesonide Study Group. AB - The effect of budesonide, 1, 2, and 4 mg/100 ml in daily enemas, on active distal ulcerative colitis was compared with that of prednisolone disodium phosphate enemas, 25 mg/100 ml, in a multicentre, randomized, group-comparative trial. A total of 146 patients with active disease were treated for 2 weeks. Data from 139 were valid for statistical analyses. Bowel habits, proctoscopy findings, and histologic pictures were evaluated, and plasma cortisol was determined for measurement of influence on the hypothalamic-pituitary-adrenal axis. Clinical symptoms and proctoscopy findings improved within all treatment groups. The improvement of these effect variables tended to be less after treatment with the lowest dose of budesonide, 1 mg/100 ml, than after the other treatments. Plasma cortisol did not change in any of the budesonide groups, whereas a mean reduction of 30% (P = 0.07) was observed after prednisolone. It can be concluded that budesonide enemas of 2 mg/100 ml constitute an attractive alternative to prednisolone enemas for topical treatment of distal ulcerative colitis. PMID- 1763293 TI - Inhibition of gastrin release induced by fundic distension. Evidence of a defective inhibition in duodenal ulcer patients. AB - The serum gastrin response to an infusion of gastrin-releasing peptide (GRP), with or without simultaneous fundic distension, was studied in healthy volunteers and in patients with duodenal ulcer disease before and after a complete proximal gastric vagotomy (PGV). We also studied the effect of fundic distension alone on gastrin release and intraluminal gastric pressure in healthy volunteers and in patients after PGV. We observed an increased intraluminal pressure in patients after PGV compared with healthy subjects. During fundic distension with 600 ml of air no significant increase in gastrin values was observed in healthy subjects or in duodenal ulcer patients. In healthy subjects fundic distension significantly inhibited the gastrin response to the higher dose of GRP. This inhibitory effect exerted by fundic distension was counteracted by cholinergic blockade. In contrast, fundic distension did not alter the gastrin response to GRP in duodenal ulcer patients, suggesting a defective inhibitory mechanism in duodenal ulcer patients. After PGV, GRP infusion resulted in an enhanced gastrin response, and fundic distension seemed to facilitate the gastrin-stimulatory effect of GRP. This supports the concept of a vagally dependent inhibitory oxyntopyloric mechanism and that fundic distension can elicit both inhibitory and stimulatory secretory mechanisms. PMID- 1763294 TI - Mucosal surface area of a reversed intestinal segment in rats. AB - Only scarce knowledge exists of morphologic changes after antiperistaltic reversal of the small intestine. Previous animal models using a reversed segment of the small intestine after massive intestinal resection have been mostly concerned with assessing absorption. A rat model was therefore developed for the purpose of studying mucosal surface area in the small intestine after reversal of an intestinal segment. A reversal of 10 cm, representing a length of about 10%, was found suitable for the investigation. Marked dilatation of the reversed segment occurred. A pronounced increase in mucosal surface area caused by mucosal hyperplasia was observed. The mucosal surface area in an anastomosed, but not reversed, segment also increased markedly compared with a group undergoing no operation, although less than in the reversed segment. We conclude that a reversed intestinal segment will increase mucosal surface area in an optimal length used for this purpose. This increase is possibly caused by prolonged exposure to intestinal chyme. PMID- 1763295 TI - Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. AB - The incidence of ulcerative colitis was estimated during the period 1962 to 1987 in the county of Copenhagen. Within this area of approximately 550,000 inhabitants, 1161 patients were diagnosed. The mean annual incidence for the period was 8.1 per 10(5) inhabitants. There were significant increases in incidence in the early 1970s and in the early 1980s, both of which were followed by significant decreases. A bimodal age distribution was found in men, with incidence peaks in young adult life and late in life. In women a peak incidence was found in the young adult age group. The interval from onset of symptoms to diagnosis in terms of years remained unchanged over the period, with a median of 1 year (range, 0-37 years). The extent of disease at diagnosis was total colon in 18% of the patients, a substantial part of the colon in 36%, and distal colon in 44%--with no changes during the study period. The distribution of different localizations did not differ among age groups except for a tendency towards more extensive disease in young patients, below 20 years of age. The disease activity in the 1st year was fulminant in 9.1% of the cases, moderate to high in 70.7%, and low in 20.2%, with a tendency towards higher activity in patients diagnosed late in the study period. The prevalence of ulcerative colitis increased steadily during the study period, reaching a value at the end of the study (31 December 1987) of 161 per 10(5) inhabitants. PMID- 1763296 TI - Scintigraphic determination of gastrointestinal transit times. A comparison with breath hydrogen and radiologic methods. AB - A scintigraphic method for determination of gastrointestinal transit times was compared with the breath hydrogen test and a multiple-bolus, single-radiograph technique. A close temporal association was found between the caecal appearance of radioactivity and the onset of breath hydrogen excretion in eight healthy subjects. Neither mean small-intestinal nor mean orocaecal transit times of the radiolabelled marker were correlated with the magnitude of hydrogen peak, hydrogen peak time, or the area under hydrogen curve. No correlation was noted between whole-gut transit time of the radiolabelled marker and mean whole-gut transit time calculated from a 6-day administration of the radiopaque marker in 16 healthy subjects. The stool weight was inversely correlated with the mean colonic (r = -0.46, p = 0.009) and the mean whole-gut (r = -0.45, p = 0.011) transit times of the radiolabelled marker. In conclusion, inadequate delineation of the caecal region seems to be an unimportant drawback of the scintigraphic measurements, whereas day-to-day variation in gastrointestinal transit rates may influence the reliability of the assessments. Probably, quantitative transit data cannot be obtained from the breath hydrogen concentration profiles. PMID- 1763297 TI - Effect of biliary tract procedures on duodenogastric reflux and the gastric mucosa. AB - The effect of alterations in the biliary tract on the gastric milieu was evaluated in gallstone disease and after cholecystectomy or biliary fenestration and compared with a control group. Endoscopic bile reflux was often found in gallstone patients (67%) and almost always after cholecystectomy (89%). Gastric bile acid concentrations were greater in the gallstone patients than in the control patients, were higher still after cholecystectomy, and were highest after biliary fenestration. The pH of the gastric fluid was more alkaline in the cholecystectomized groups. Lysolecithin concentrations were generally low and did not differ between the groups, nor was there any difference in scintigraphic reflux between the groups. Endoscopic erythematous gastritis correlated with the grade of bile reflux and was a common finding after biliary tract procedures. There were no consistent histologic findings associated with duodenogastric reflux. Helicobacter pylori colonization rates were similar in the various patient groups and were not affected by the reflux grade. PMID- 1763298 TI - Gallbladder sensitivity to cholecystokinin in coeliac disease. Correlation of gallbladder contraction with plasma cholecystokinin-like immunoreactivity during infusion of cerulein. AB - The present study was undertaken to determine whether alterations in the gallbladder sensitivity to cholecystokinin (CCK), apart from a reduced endogenous CCK secretion, contribute to the abnormally decreased postprandial gallbladder contraction in patients with coeliac disease. Gallbladder emptying, measured by cholescintigraphy, and plasma CCK levels, measured by radioimmunoassay, were studied during infusion of graded doses of the CCK analog cerulein in six coeliac patients with subtotal villous atrophy, six coeliac patients on a gluten-free diet with normal villous architecture, and nine control subjects. Both in the patients and in the controls infusion of stepwise increasing doses of cerulein, in the range of 1-16 ng.kg-1.h-1, induced dose-related changes in plasma CCK-like immunoreactivity (CCK-LI) (r = 0.99; p less than 0.001) and gallbladder emptying (r greater than 0.97; p less than 0.01-p less than 0.001). Plasma CCK-LI and gallbladder responses were not significantly different among untreated coeliac patients, treated coeliac patients, and controls. Gallbladder sensitivity to cerulein in untreated and treated coeliac patients was not significantly different from that in controls. It is concluded that the abnormally decreased gallbladder contraction in coeliac patients is the result of a reduced endogenous CCK secretion and not of a lack of end-organ responsiveness to CCK. PMID- 1763299 TI - Risk of recurrence and reoperation after resection for ileocolic Crohn's disease. AB - To evaluate possible risk factors for recurrence after primary resection of ileocolic Crohn's disease, the clinical course of 48 consecutive patients operated on over a 27-year period were reviewed. Median follow-up was 10 years (range, 3-27 years). The probability of not having a recurrence and the probability of not undergoing a second resection were 0.476 (+/- 0.191, 95% confidence limits) and 0.701 (+/- 0.180), respectively, after 10 years. None of the possible risk factors examined--sex, age at the primary resection, length of preoperative history, length of bowel involvement, failure of preoperative medical treatment, and residual microscopic disease at resections lines- significantly influenced the risk of recurrent disease (P greater than 0.05, log rank test); however, there was a trend towards a higher risk of recurrence for the patients who had received medical treatment preoperatively. In the present study it was not possible to identify any factors that influenced the risk of recurrence. PMID- 1763300 TI - [Thrombocyte-vascular wall interaction and coronary heart disease]. AB - The interaction of platelets with the vessel wall plays an important pathophysiological role in coronary artery disease. While in healthy blood vessels platelets remain inactivated and do not adhere or aggregate, an augmented interaction occurs in coronary artery disease. Due to their strategic anatomical position between the circulating blood and the media of the vascular wall, endothelial cells play an important regulatory role. Indeed, after endothelial denudation, massive platelet adhesion and aggregation at the vessel wall occurs. Platelet-derived substances lead to vasoconstriction and in the long run also to proliferative changes of the vascular wall. Besides other substances, endothelial cells release vasoactive mediators such as endothelium-derived nitric oxide (NO), prostacyclin and endothelin. In healthy human arteries, aggregating platelets cause endothelium-dependent relaxations in spite of the liberation of serotonin and thromboxane A2 and through the luminally released NO also induce a feedback inhibition of the platelets. In contrast, in arteries without endothelium, a marked vasoconstriction (due to thromboxane A2 and serotonin) is noted. Endothelin may also play a role in platelet-vessel wall interaction, since thrombin and transforming growth factor beta (a platelet-derived product) stimulate the production of this potent vasoconstrictor. Oxidized low-density lipoproteins inhibit the relase of NO and thereby activate the platelet-vessel wall interaction. In atherosclerosis even more pronounced dysfunctions of the endothelium occur, which lead to vasoconstriction, ischemia and thrombus formation in patients with coronary artery disease. PMID- 1763301 TI - [Drug therapy prevention of coronary sclerosis]. AB - Primary preventive drug treatment of coronary artery disease (CAD) has gained importance in recent years as more efficient lipid lowering drugs and substances with new mechanisms become available, e.g. calcium entry blockers and antioxidants. For lipid lowering drugs, the exact mechanism of action is still not clear; the results of quantitated coronary angiography (QCA) revealing a small but significant increase in luminal size in stenotic areas can be explained both by stabilization of endothelial function (increased EDRF production)--as demonstrated in animal studies--leading to a decrease in basal tone, and by a decrease in plaque volume (so far not evidenced by QCA in man). Calcium entry blockers and antioxidants inhibit the formation of new atherosclerotic lesions, mainly by improving cholesterol excretion from vascular smooth muscle cells and macrophages into the extracellular space, and by suppression of proliferation and differentiation of vascular smooth muscle cells. The ensuing reduction of cardiac events is not yet proven for calcium entry blockers and also needs further confirmation for lipid lowering drugs; the difficulty of studies looking for clinical endpoints (myocardial infarction on sudden coronary death, unstable angina) lies in the very slow anatomical progression of CAD as demonstrated by QCA, demanding large numbers of patients and long intervals to demonstrate statistical significance. PMID- 1763302 TI - [Aortoiliac occlusive disease: yesterday and today]. AB - The surgical management of aortoiliac atherosclerotic occlusive disease includes endarterectomy and prosthetic by-pass in either the anatomical or extraanatomical position. Aortoiliac endarterectomy is only indicated in localized disease which spares the external iliac artery and does not exhibit aneurysmal changes. Prosthetic by-pass is easier to perform, but carries graft-related risks including anastomotic pseudoaneurysms in 5 to 10% of cases at 10 years. Extraanatomical shunts are performed when there are general or abdominal contraindications to an anatomical by-pass. Simultaneous revascularisation of the aortic visceral branches mainly involves the renal, inferior mesenteric and hypogastric arteries. Correction of celiac and superior mesenteric artery stenosis is less frequently indicated. The appropriate approach and surgical technique depend on the artery and the lesion involved. Suprarenal implantation of aortoiliac by-passes is performed at the celiac, descending aortic and ascending aortic levels. Indications include suprarenal coarctation of the aorta, reoperation following ligature of the juxtarenal aorta, and some cases of extensive thoracoabdominal atherosclerosis. The surgical management of aortoiliac occlusive disease in 353 patients treated in our clinic between 1976 and 1986 is reported. Mean follow-up exceeded 5 years. Operative mortality for endarterectomy (15 patients) was nil, and was 3.9% for by-pass graft. Early complication rate was 6.5% and late complication rate 23.2%. Half of the late complications were due to progression of the atherosclerotic process. Pseudoaneurysms at the aortic (3.1%) and femoral (9.9%) levels occurred between the fifth and tenth years. Prosthesis infection occurred shortly after operation in 3 patients and much later in 2 patients. PMID- 1763303 TI - Conservative mitral valve surgery: has the progress changed the indications? AB - Cardiac valve replacement still means replacement of one disease by another. Thromboembolic complications in the case of mechanical valves, as well as restenosing and calcification of bioprostheses, are major causes of further morbidity and mortality. Hence valve reconstruction, where indicated, represents an attractive alternative. In the late 1960s mitral valve reconstruction received new impetus from Carpentier through a number of techniques based on a multifactorial concept of mitral valve pathology. Although initially other surgery groups showed little enthusiasm for this approach, more recently a marked trend towards valve-preserving surgery has been observable. The experience of Carpentier and others, including our own, has provided better medium and long term results with mitral reconstruction compared to valve replacement, in regard to all indices of valve function except the reoperation rate, which is higher after valve reconstruction. It can also be shown that the results of reconstruction of rheumatically damaged valves are less good than in non rheumatic valve diseases and in particular myxomatous mitral valves. On the other hand, rheumatic populations are as a rule young and show poor compliance in taking medication, especially anticoagulants, which is why in these cases valve replacement is even less attractive. Although valve reconstruction is subject to a marked learning curve, it is possible to take advantage of others' experience. Several new surgical techniques have been developed and others are being adapted to new needs. Together these two factors have helped to make valve reconstruction a more reliable and reproducible method. The improved results have changed the indication for valve replacement, in that nowadays an attempt is made to reconstruct the valve before left ventricular hemodynamics are irreversibly damaged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763304 TI - [Hemodynamics of various heart valve prostheses]. AB - Modern tilting disc and bileaflet prostheses, and bio-prostheses, perform similarly regarding pressure gradients, discharge coefficient and performance index; however, only bio-prostheses increase their opening area with increasing flow. Ball valve prostheses of the Starr-Edwards type perform less satisfactorily with higher pressure gradients and lower performance indices, which may result in less favorable long-term follow-up. Bio-prostheses show degenerative changes with increasing age which, over a period of 7-10 years, can lead to clinically relevant stenoses necessitating reoperation. PMID- 1763305 TI - [Mechanical circulatory support today]. AB - Invasive mechanical circulatory support is the approach of choice in patients with acute myocardial failure resistant to conventional therapy. Today survival rates between 24% for postcardiotomy cardiac failure and 40% for bridge to heart transplantation can be achieved. However, a broad armamentarium of devices for mechanical circulatory support is necessary to provide optimum assistance for the failing heart in the various clinical situations. The available devices and their potential indications and limitations are reviewed. PMID- 1763306 TI - Surgery for supraventricular tachyarrhythmias. AB - Since the first successful surgical intervention for Wolff-Parkinson-White syndrome by W. C. Sealy, a surgical electrophysiological intervention has been developed for every single supraventricular arrhythmia. The surgical rationale is based on the site of the mechanism of the arrhythmia and associated pathology which characterizes the "arrhythmogenic substrate". Wolff-Parkinson-White syndrome is a congenital heart disease characterized by an accessory atrioventricular connection distinct from the AV node-His bundle system. It is associated with AV reentrant tachycardia and/or atrial fibrillation with fast ventricular responses via the accessory pathway. The current surgical management is ablation of the accessory pathway using either an endocardial dissection or epicardial approach. Surgical ablation is associated with high efficacy and low morbidity. Epicardial dissection of the accessory pathway on the beating heart has helped to localize variant accessory pathways associated with Coumel's tachycardia or Mahaim's fiber electrophysiological entity. AV nodal reentrant tachycardia can be cured using direct AV nodal dissection (or perinodal cryoablation). Atrial flutter can be interrupted by cryoablation of the arrhythmogenic substrate located in the coronary sinus orifice of the region modifying atrial inputs. Chronotropic atrial function abolished by chronic or paroxysmal idiopathic atrial fibrillation can be restored using the corridor operation (sinus node-AV node insulation). Surgery is an alternative in patients with resistant atrial tachycardias. Currently surgery is indicated only after other non-invasive EP interventions have been either attempted or rejected. PMID- 1763307 TI - [AIDS--a dangerous pandemic]. PMID- 1763308 TI - [Fluoride excretion in schoolchildren with differing systemic fluoride care]. AB - The aim of the present study was to collect data on urinary fluoride output in 8 16-year old students exposed to either drinking water fluoridation (DWF), or domestic salt fluoridation (DSF). Spot urine samples were collected in the canton of Basel-Stadt (DWF, n = 123), in the canton of Berne (DSF, n = 264), in the county of Davos (DSF, n = 241), and in the city of Winterthur (DSF, n = 40). Furthermore, fluoride concentrations were determined in plasma samples drawn from 33 students from Winterthur. The urinary fluoride concentrations were higher in Basel and Davos (0.62 +/- 0.35 mg/l; 0.61 +/- 0.42 mg/l) than in Berne and Winterthur (0.46 +/- 0.42 mg/l; 0.50 +/- 0.31 mg/l). A relatively high natural fluoride content (0.3 mg/l) in the drinking water explained the difference in urine fluoride concentration between students from Davos and the two other regions with domestic salt fluoridation (Berne, Winterthur). The average fluoride concentration in plasma was 12.7 +/- 3.8 ng/ml. We concluded that, in general, the supply with fluoride consumed with fluoridated domestic salt is close to the level obtained with drinking water fluoridation. However, in areas with very low systemic fluoride supplementation through the drinking water this level might not be reached with salt as the only source of systemic fluoride. Also, the data confirmed the safety of domestic salt fluoridation. PMID- 1763309 TI - [The Perioplaner/Periopolisher. The loss of substance on the root surface and the initial clinical experiences]. AB - A new system for the removal of supragingival and subgingival plaque and calculus was studied. The system involves two motor driven handpieces. One handpiece works with curettes and hoes (Perioplaner) and the other works with diamond-layered instruments (Periopolisher). In the first part of this study the loss of root substance was measured as a consequence of treatment by these motor-driven instruments. These results were compared with those using classical hand curettes and rotating diamonds (Perio-Set). In the literature there is still debate over whether it is necessary to remove not only plaque and calculus but also cementum which may contain endotoxin or may even be infected. Whatever opinion one may have, it must be known how much root substance is lost by using a particular scaling instrument. This study has shown that the use of the Perioplaner and Periopolisher results in about the same loss of root substance as the use of hand instruments. In the second part of this study, first clinical experiences with these instruments are reported. PMID- 1763310 TI - Long-term stability of treatment results in cleft lip and palate patients. AB - The stability of the orthodontic and prosthetic results of the treatment of 18 individuals with isolated cleft of the palate, 18 subjects with a complete unilateral and 8 with a complete bilateral cleft was evaluated in an eight-year follow-up period. The subjects were examined at the age of 19 years, after completed orthodontic and surgical treatment, and again at the age of 27 years. After the first examination the majority of the individuals with a complete cleft had at the age of 20 to 21 years been treated with a fixed bridge which was only minimally extended. The width of the upper dental arch at the second bicuspid decreased slightly in the subjects with an isolated cleft of the palate and in those with a bilateral cleft. In the subjects with a unilateral cleft there was a slight decrease of the upper dental arch widths at both bicuspids and at the first molar. In the subjects with complete clefts the slight decrease in upper dental arch widths was accompanied by a slight increase of the number of posterior teeth in cross-bite. The total number of teeth in cross-bite was small, however. On the whole, the upper dental arch was relatively stable during the follow-up period. This was found in the group with bilateral clefts, reconstructed with 5-8 unit bridges, as well as in the subjects with a unilateral cleft who had received no or only minimally extended reconstructions and in the group with an isolated cleft of the palate (no bridge). PMID- 1763311 TI - [The symptomatic therapy of cervical hard-substance defects with dentin-adhesive composite systems]. AB - For covering of hypersensitive, morphologically disturbed and non-esthetic cervical (wedge-shaped) defects of hard dental tissues, dentine adhesive composite systems are suitable for a careful and less invasive preparation. Presumption is a smooth and at probing hard-touched defect surface. A clinical 2 year study (15 patients with 143 cervical lesions) using 5 different dentine adhesive composite systems resulted in superiority of the hybrid composite P-30 in view of low filling losses (after 1 year: 1 of 28 fillings after 2 years: 2 of 27 fillings), the acceptable bond zone morphology (after 1 and 2 years clinical intact bond zones), and a constant volume behaviour (after 1 and 2 years no clinical changes of volume). The micromorphological evaluation correlated in a lot of cases with the clinical findings after 2 years. It has to be expected that improved dentine adhesive composite systems together with changed setting mechanisms of dentine adhesives will be able to eliminate filling losses in the treated indication. PMID- 1763312 TI - [The Turbocid. An apparatus for the cleaning, disinfection and lubrication of handpieces, anglepieces and turbines]. PMID- 1763313 TI - [The uses of the EVA system (II). The different potential uses of the vibration grinding principle in dental practice]. PMID- 1763314 TI - [The prevention of AIDS: possibilities and limits]. PMID- 1763315 TI - ["We are putting the accent on continuing education". Interview by Kurt Venner]. PMID- 1763316 TI - The Human Genome Project and patents. PMID- 1763317 TI - Respect for vitamin C. PMID- 1763318 TI - New AIDS drug poised to move into development. PMID- 1763319 TI - Soviet science: a struggle for survival. PMID- 1763320 TI - Breast cancer: stalemate in the war on cancer. PMID- 1763321 TI - Fight erupts over DNA fingerprinting. PMID- 1763322 TI - HIV risk higher for first-born twins. PMID- 1763323 TI - The utility of DNA typing in forensic work. PMID- 1763324 TI - Linkage of faulty major histocompatibility complex class I to autoimmune diabetes. AB - Pancreatic islet cells are the targets of an autoimmune response in type I diabetes. In the nonobese diabetic (NOD) mouse model of autoimmune diabetes, expression of major histocompatibility complex (MHC) class I proteins was inversely correlated with diabetes; in this mouse a mutation in the MHC class II linked gene for the putative MHC class I peptide transporter was also present. Mice deficient in MHC class I expression because they do not produce beta 2 microglobulin also developed late onset autoimmune diabetes. In cells from humans with type I diabetes expression of MHC class I was decreased; subsets of prediabetics categorized as most likely to become hyperglycemic also had low MHC class I. T cell responses to self antigens are faulty in diabetics. In sets of genetically identical twins that are discordant for diabetes, the defect appeared to reside with the antigen presenting cell. Thus, a lack of surface MHC class I protein is associated with autoimmune diabetes; the concomitant defect in antigen presentation may impair the development of self tolerance, which could result in autoimmune disease. PMID- 1763325 TI - Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. AB - Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF 1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex. PMID- 1763326 TI - A fungal gene for antibiotic resistance on a dispensable ("B") chromosome. AB - A family of cytochrome P-450 (Pda) genes in the pathogenic fungus Nectria haematococca is responsible for the detoxification of the phytoalexin pisatin, an antimicrobial compound produced by garden pea (Pisum sativum L.). The Pda6 gene was mapped by electrophoretic karyotype analysis to a small meiotically unstable chromosome that is dispensable for normal growth. Such traits are typical of B chromosomes. The strains of Nectria studied here have no sequences that are homologous to the Pda family other than Pda6 and therefore demonstrate that unique, functional genes can be found on B chromosomes. Unstable B chromosomes may be one mechanism for generating pathogenic variation in fungi. PMID- 1763327 TI - Identification and characterization of zinc binding sites in protein kinase C. AB - Metal ion coordination in the regulatory domain of protein kinase C (PKC) is suggested by the conservation of six cysteines and two histidines in two homologous regions found therein. By monitoring x-ray fluorescence from a purified sample of rat PKC beta I overexpressed in insect cells, direct evidence has been obtained that PKC beta I tightly binds four zinc ions (Zn2+) per molecule. Extended x-ray absorption fine structure (EXAFS) data are best fit by an average Zn2+ coordination of one nitrogen and three sulfur atoms. Of the plausible Zn2+ coordination models, only those featuring nonbridged Zn2+ sites accommodate the EXAFS data and all of the conserved potential ligands. PMID- 1763328 TI - Maintenance of normoglycemia in diabetic mice by subcutaneous xenografts of encapsulated islets. AB - The goal of islet transplantation in human diabetes is to maintain the islet grafts in the recipients without the use of immunosuppression. One approach is to encapsulate the donor islets in permselective membranes. Hollow fibers fabricated from an acrylic copolymer were used to encapsulate small numbers of rat islets that were immobilized in an alginate hydrogel for transplantation in diabetic mice. The fibers were biocompatible, prevented rejection, and maintained normoglycemia when transplanted intraperitoneally; hyperglycemia returned when the fibers were removed at 60 days. Normoglycemia was also maintained by subcutaneous implants that had an appropriately constructed outer surface on the fibers. PMID- 1763329 TI - Low affinity interaction of peptide-MHC complexes with T cell receptors. AB - The interaction of antigen-specific T cell receptors (TCRs) with their ligands, peptides bound to molecules of the major histocompatibility complex (MHC), is central to most immune responses, yet little is known about its chemical characteristics. The binding to T cells of a labeled monoclonal antibody to the TCR was inhibited by soluble class II MHC heterodimers complexed to different peptides. Inhibition was both peptide- and TCR-specific and of low affinity, with a KD = 4 x 10(-5) to 6 x 10(-5) M, orders of magnitude weaker than comparable antibody-antigen interactions. This finding is consistent with the scanning nature of T cell recognition and suggests that antigen-independent adhesion precedes TCR engagement. PMID- 1763330 TI - Inhibition of Rap1A binding to cytochrome b558 of NADPH oxidase by phosphorylation of Rap1A. AB - Rap1A is a low molecular weight guanosine triphosphate (GTP)-binding protein in human neutrophil membranes whose cellular function is unknown. Rap1A was found to form stoichiometric complexes with the cytochrome b558 component of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system. The (guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S)-bound form of Rap1A bound more tightly to cytochrome b558 than did the guanosine diphosphate-bound form. No complex formation was observed between cytochrome b558 and H-Ras-GTP-gamma-S or Rap1A-GTP-gamma-S that had been heat-inactivated, nor between Rap1A-GTP-gamma-S and hydrophobic proteins serving as controls. Complex formation between Rap1A-GTP gamma-S and cytochrome b558 was inhibited by phosphorylation of Rap1A with cyclic adenosine monophosphate (cAMP)-dependent protein kinase. These observations suggest that Rap1A may participate in the structure or regulation of the NADPH oxidase system and that this function of the Rap1A protein may be altered by phosphorylation. PMID- 1763331 TI - Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist. AB - The human immunodeficiency virus-1 (HIV-1) trans-activator Tat is an attractive target for the development of antiviral drugs because inhibition of Tat would arrest the virus at an early stage. The drug Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H 1,4-benzodiazepine-2(H)-one], inhibited gene expression by HIV-1 at the level of transcriptional trans-activation by Tat. The compound did not inhibit the basal activity of the promoter. Both Tat and its target sequence TAR were required for the observed inhibitory activity. Ro 5-3335 reduced the amount of cell-associated viral RNA and antigen in acutely, as well as in chronically infected cells in vitro (median inhibition concentration 0.1 to 1 micromolar). Effective inhibition of viral replication was also observed 24 hours after cells were transfected with infectious recombinant HIV-1 DNA. The compound was active against both HIV-1 and HIV-2 and against 3'-azido-3'-deoxythymidine (AZT)-resistant clinical isolates. PMID- 1763332 TI - House of Delegates reaffirms voluntary, confidential testing for HIV. PMID- 1763333 TI - Disordered energy and protein metabolism in liver disease. AB - Although progress has been made, more information is needed on the role of nutritional therapy in liver disease. Because considerable heterogeneity exists among patients regarding both nutritional needs and the pathophysiology of malnutrition, their nutritional status must be monitored to permit careful selection and individualization of therapy. It is important to remember that the factors controlling nutritional status and overall survival in cirrhosis are multifactorial and the pathophysiologic mechanisms influencing outcome remained to be further defined. Consequently, it seems unlikely that any single therapy will be effective alone. In this regard, it should be emphasized that nutritional management should not be aimed solely at restoring normal metabolic homeostasis but should maximize anabolic regenerative processes in addition and minimize abnormal liver function so as to promote the effectiveness of other interventional therapies in patients with chronic liver disease. PMID- 1763334 TI - Nutritional therapies in liver disease. PMID- 1763335 TI - Role of nutrition in hepatic encephalopathy. PMID- 1763336 TI - Impact of malnutrition and its therapy on liver transplantation. AB - The consequences of malnutrition and impact of nutritional support on the liver transplant patient have not been adequately addressed in clinical research studies. As we have gained experience in assessing patients for transplantation surgery, the risks of malnutrition have been realized. Part of the success of liver transplantation today is related to improved timing of surgery, patient selection, and perioperative management. Malnutrition is one of the adverse risk factors that is potentially reversible and therefore specialized nutritional support techniques should be able to improve postsurgical outcome. However, the performance and interpretation of nutritional research has been impeded by difficulties in separating the effects of liver dysfunction from disturbances secondary to nutritional deficiencies; for example, hypoproteinemia would be a consequence of both. Through the use of multivariate prognostic formulas and development of better nutritional indices for patients with liver disease, it should be possible to identify those patients who will receive the greatest benefit from preoperative and perioperative nutritional support. Furthermore, the kinds of nutritional supplementation having the greatest impact could then be determined. PMID- 1763337 TI - Nutrition, hormones, metabolism, and liver regeneration. PMID- 1763338 TI - Trace metals in liver disease. PMID- 1763339 TI - Interaction between alcohol and nutrition in the pathogenesis of alcoholic liver disease. PMID- 1763340 TI - The pain of parturition. PMID- 1763341 TI - Options for labor analgesia: techniques of epidural and spinal analgesia. AB - The results of the clinical research evaluating techniques of labor analgesia suggest that drug combinations hold much promise for providing excellent analgesia for labor, while minimizing the adverse effects associated with each technique. With the various combinations of drugs and techniques available, the anesthesiologist is better able to customize the control of pain for each parturient. PMID- 1763342 TI - Does epidural anesthesia affect the course of labor and delivery? AB - The progress of labor ideally leads to a normal, spontaneous, vaginal delivery. Many factors--maternal, fetal, obstetrical and anesthetic--may collectively contribute to delaying or precluding an ideal outcome. Adverse outcomes of labor and delivery must be clearly defined in terms of maternal, fetal, or neonatal morbidity or mortality, and should be distinguished from abnormal data (such as fetal heart rate, duration of labor, and incidence of low forceps deliveries) that are only indirectly related to outcome. Epidural anesthesia is not a singular phenomenon. Variations and subtle nuances in the administration of epidural anesthesia create a vast array of potential anesthetic regimens. To discover the anesthetic methods that provide excellent analgesia with no adverse effects on the course of labor is an ideal goal that has not yet been achieved. To approach this goal, the answers to several questions are needed. Are study patient groups adequately matched for risk factors? Are obstetrical practices well-defined with respect to elective versus indicated use of instrumental or cesarean delivery methods? Do the risks of instrumental delivery outweigh the benefit of perineal analgesia associated with epidural anesthesia? Is it possible to provide optimal analgesia throughout stage two labor without tending to increase the risk of instrumental delivery? Can delayed pushing during stage two labor increase the probability of spontaneous vaginal delivery with continuous epidural anesthesia? Well-controlled clinical trials and refinements in both anesthetic and obstetric techniques are necessary to resolve such issues so that every parturient (and fetus) may undergo a safe and painless delivery. PMID- 1763343 TI - Alternatives to epidural analgesia. PMID- 1763344 TI - General anesthesia and maternal mortality. PMID- 1763345 TI - Anesthetic concerns in the patient with preeclampsia. AB - Preeclampsia is a disease of unknown etiology and a major contributor to maternal and neonatal morbidity and mortality. With severe preeclampsia, numerous factors including intravascular volume depletion and susceptibility of developing pulmonary edema complicate anesthetic management. Invasive monitors such as CVP or PA pressure measurements are often required for guiding fluid management. When possible, lumbar epidural blockade is the preferred method for providing analgesia and anesthesia. Under all circumstances, a collegial and collaborative approach between obstetrician and anesthesiologist facilitates optimum patient care. PMID- 1763346 TI - Anesthesia for procedures involving the fetus. PMID- 1763347 TI - Principles of analgesia in the neonate. PMID- 1763348 TI - [Study of the right heart and external respiratory functions in patients with liver cirrhosis by Doppler echocardiography]. AB - The paper presents clinical and instrumental evidence on 47 patients with hepatic cirrhosis. The revealed ventilatory disorders and worse bronchial permeability closely correlated with the degree of pulmonary hypertension which in its turn depended on portal hypertension degree. Pulmonary hypertension decreased with a decline in the activity of the pathological process in the liver due to treatment. External respiration insufficiency observed in hepatic cirrhosis contributes to the onset of arterial hypoxemia and hypoxic impairment of the liver activating in it a pathological process. It is recommended that such patients should receive a combined treatment incorporating oxygen therapy, calcium antagonists, antioxidants. PMID- 1763349 TI - [Various neurohumoral aspects of hemodynamic changes in patients with hypertension after correction of electrolyte disorders]. AB - Changes in activity of sympathetic-adrenal and + renin-angiotensin-aldosterone systems (SAS and RAAS), hemodynamics and electrolyte metabolism when correcting sodium balance in consideration of their "salt sensitivity" were studied in 83 hypertension stage I and II patients. In moderate restriction of sodium chloride response of the patients was not uniform. "Salt--sensitive" subjects responded positively with improvement of central and peripheral hemodynamics, electrolyte balance in enhanced activity of SAS and RAAS. In salt nonresponders and in paradoxical sensitivity SAS and RAAS show activation, most distinct in paradoxical sensitivity, and worse central and peripheral hemodynamics, electrolyte imbalance. PMID- 1763350 TI - [Analysis of the profiles of functional psychomotor asymmetry and mental stress in patients with cardiovascular diseases]. AB - The profile of functional sensomotor asymmetry (FSMA) was evaluated by a series of tests and inversion of emotional reflection. Altogether 70 healthy subjects and 114 cardiovascular diseases patients were examined. Among the patients there were 36 subjects with acute myocardial infarction, 28 with coronary heart disease, 26 with borderline hypertension and 24 with neurocirculatory dystonia (NCD). The highest emotional tension was recognized in myocardial infarction and coronary heart disease. NCD patients exhibit the left FSMA profile more frequently than healthy subjects. PMID- 1763351 TI - [Status of phosphorus-calcium metabolism and secretion of calcium- regulating hormones in diabetic nephropathy]. AB - The studies performed by the authors led them to the conclusion that diabetic nephropathy aggravates derangement of phosphoric--calcium metabolism in patients with diabetes mellitus. Secondary hyperparathyroidism, as a result of negative calcium balance in decompensated diabetes mellitus and renal dysfunction, contributes to development of marked alterations of the osteoarticular system. PMID- 1763352 TI - [Indications for using a new magnetotherapeutic method in arterial hypertension]. PMID- 1763353 TI - [Biosorption with extracorporeal use of heterologous spleen in the complex treatment od suppurative-septic diseases]. AB - The search for new methods in the control of purulent infection is highly topical nowadays. For this purpose a complex of intensive therapy is suggested involving hemosorption via the patient's blood perfusion through porcine heterospleen. By literature and experimental data this technique is not inferior in efficacy to the use of the donor spleen. The spleen is removed conventionally, in modification of the authors. The results of the hemosorption analysed on 82 procedures performed in 1989-1990 justify employment of the above hemosorption in view of its efficacy, availability, simplicity. PMID- 1763354 TI - [Glutathione levels and the activity of the enzymes of glutathione metabolism in erythrocytes of patients with acute cholecystitis]. AB - It is shown that in acute cholecystitis patients versus chronic cholecystitis ones and donors, the total glutathione in blood is lower while the activity of glutathione metabolism enzymes in red blood cells inhibited. Enzymological findings correlate with clinical symptoms of intoxication. Surgery aggravates disturbed activity of the enzymes. Conventional conservative therapy is not effective in normalizing the enzymes activity either. A good therapeutic response can be achieved by a directed transport of antibiotics in autologous blood ghosts which promotes recovery of normal activity of glutathione metabolism enzymes, routine glutathione level, early stabilization of hepatocytic membranes beneficial for surgical patients. PMID- 1763355 TI - [Metabolic disorders in peritonitis: hemodynamic or cellular disorders?]. AB - Systemic and hepatic hemodynamics, gas exchange, acid-base balance in blood from the artery, portal, hepatic and peripheral veins were examined in 113 patients with diffuse peritonitis varying etiologically. In view of adequate tissue perfusion and oxygen transport revealed it is suggested that causes of metabolic derangement arising in peritonitis and responsible for multiple organ insufficiency should be searched into at the level of intracellular metabolism. PMID- 1763356 TI - [Combined treatment of cancer of the stomach using a specific immunotherapy]. AB - Autoinoculation is suggested as an adjuvant means to augment the effect of surgery in gastric cancer which may prevent the development of recurrences and metastases. Surgery alone is not a curative method and 5-year survival in gastric cancer stage III ranges from 9.2 to 28%. The data have been obtained on comparative survival in a control group and a group of inoculated patients. The greatest effect was achieved in patients with poorly differentiated adenocarcinoma. Further investigation of the two groups adjusted for the patients' age, kind of surgery and morphological structure of the tumor will help to work out precise criteria for inoculation. PMID- 1763357 TI - [Predicting the probable passage of common bile duct calculi in patients with mechanical jaundice]. AB - The authors propose a mathematical method of predictingthe passage of common bile duct calculi. An original mathematical formula derived by a computer allows a 98% accuracy of the prognosis. The estimations were based on the principal parameters influencingthe choledochal calculi movement defined with the help of the regression analysis. Such prediction simplifies the choice of therapeutic policy in mechanical jaundice due to choledocholithiasis. PMID- 1763358 TI - [Pathogenesis of diffuse toxic goiter]. PMID- 1763359 TI - [Organizational aspects of the prevention of strokes]. PMID- 1763360 TI - [Importance of bacteriological control of surgicenters for establishing anti epidemic measures in emergency situations]. PMID- 1763361 TI - [Clinico-statistical aspects of newly detected destructive tuberculosis in the Eastern Siberia]. PMID- 1763362 TI - [Comparative evaluation of the effectiveness of antiseptics currently used in surgery]. PMID- 1763363 TI - [Experience with using UV-irradiated blood in the treatment of acute pneumonia]. PMID- 1763364 TI - [Evaluation of the degree of trauma in biliary tract surgery using a laser method in relation to the status of the plasma protease inhibitor system]. PMID- 1763365 TI - [Evaluation of the status of various indicators of body resistance in smokers]. PMID- 1763366 TI - [Prevention of suppuration of postoperative wounds in emergency abdominal laser surgery]. PMID- 1763367 TI - [Causes of mortality in acute pancreatitis and the ways of its reduction]. PMID- 1763368 TI - [Clinico-immunological and biomicroscopic parallels in neuro- rheumatism]. PMID- 1763369 TI - [Does splenectomy affect the immediate results of surgical treatment of esophageal cancer?]. PMID- 1763370 TI - [Clinical aspects of using cytological methods in oncological practice]. PMID- 1763371 TI - [Characteristics of the clinical course of malignant extra-organic tumors of the head and neck]. PMID- 1763372 TI - [Current methods of diagnosis and evaluation of dissemination of carotid chemodectoma]. PMID- 1763373 TI - [Tuberculosis of the breast detected in an oncological clinic]. PMID- 1763374 TI - [Microflora of the gastrointestinal tract in children with intestinal infections]. PMID- 1763375 TI - [Age-related characteristics of bacterial meningoencephalitis (clinico morphological studies)]. PMID- 1763376 TI - [A case of successful treatment of a patient with breast cancer using rotational electromagnetic field]. PMID- 1763377 TI - [Thrombohemorrhagic syndrome after aorto-femoral shunt]. PMID- 1763378 TI - [Treatment of pseudarthroses and ununited fractures of the scaphoid bone of the hand by using bone transplant on vascular pedicle]. PMID- 1763379 TI - [Effect of ethacizine on the heart conduction system and the indicators of central hemodynamics]. AB - A trial of the antiarrhythmic drug ethacizine made in the Soviet Union which is an analogue of ethmozine was performed in 38 patients suffering from coronary heart disease. Automatism, conduction and excitation of the myocardium, hemodynamics and the antiarrhythmic effect were studied using electrophysiological methods, echo-cardiography and Holter monitoring. Ethacizine was found effective in arrhythmia. It reduces conduction in small changes of hemodynamics and myocardial contractility. PMID- 1763380 TI - [Late outcomes of hepatitis A]. PMID- 1763381 TI - [Differential diagnosis of atypical forms of tuberculous spondylitis and tumors of the cervical segment of the spine]. PMID- 1763382 TI - [Treatment of myopathies with ribonucleotides]. PMID- 1763383 TI - Mammalian sex chromosomes. III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis in Mus musculus. AB - Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also. PMID- 1763384 TI - Beta 1-4-galactosyltransferase gene expression is regulated during entry into the cell cycle and during the cell cycle. AB - Mammalian glycosyltransferases have been implicated in a wide variety of functions besides N-linked glycosylation, including developmental processes. For this reason, we studied the effects of cell cycle and entry into the cell cycle on beta 1-4-galactosyltransferase gene expression. In this study we report that beta 1-4-galactosyltransferase (GalTase) gene expression is, indeed, regulated during the normal cell cycle, peaking during late G1-, S, and early G2 phase of the cell cycle. In addition, GalTase gene expression is regulated in a manner that resembles other "early response" genes such as jun and fos upon reentry into the cell cycle from quiescence. Finally, we show that the GalTase gene is differentially expressed during murine embryogenesis and in terminally differentiated adult tissues. It is most abundant in testis, followed by skeletal muscle and spleen. The reasons for this pattern of differential expression in adult tissues are unknown. These studies should provide important new information regarding GalTase gene expression, its regulation, and its potential link to other developmental functions. PMID- 1763385 TI - The use of irradiation and fusion gene transfer (IFGT) hybrids to isolate DNA clones from human chromosome region 9q33-q34. AB - We have generated somatic cell hybrids containing fragments of human chromosome arm 9q by an irradiation and fusion technique. No selection for human material was imposed, but of 23 clones analyzed most contained human DNA sequences and many contained multiple fragments of the human chromosome arm. A hybrid that appears to contain only two small fragments of human DNA from the regions of q33 and q34 has been used as a source from which to clone probes specific to those areas of the chromosome. PMID- 1763386 TI - Somatic cell hybridization of Roberts syndrome and normal lymphoblasts resulting in correction of both the cytogenetic and mutagen hypersensitivity cellular phenotypes. AB - Roberts syndrome (RS) is a rare recessive condition of limb deformities, growth retardation, and developmental delay. Cultured cells from approximately half of RS patients exhibit a "puffing" of the constitutive heterochromatin and a hypersensitivity to mitomycin C (MMC). Patients exhibiting these cellular phenomena are designated RS+. Somatic cell hybridization with normal cells has been shown to correct the heterochromatin abnormality in RS+ cells. To determine if the MMC hypersensitivity could also be corrected by hybridization to normal cells, we fused two different RS+ lymphoblastoid cell lines (LCLs) to a ouabain resistant, HAT-sensitive, normal LCL. Cytogenetic analyses of hybrid cell lines (HCLs) revealed complete correction of the heterochromatin abnormality. MMC cell killing assays revealed correction of the mutagen hypersensitivity as well. Five of the six HCLs tested exhibited D10 values (the dose at which 10% of the cells survive) that were not significantly lower than that of the normal parent but that were 6- to 18-fold greater than those of the RS+ parents. Correction of both of these cellular phenotypes in RS+ cells by fusion with normal cells supports the hypothesis that both of these phenomena are caused by a common defect in the Roberts syndrome gene (RBS). PMID- 1763387 TI - Kinds and locations of mutations arising spontaneously in the coding region of the HPRT gene of finite-life-span diploid human fibroblasts. AB - Spontaneous thioguanine-resistant mutants were derived from populations of finite life-span, diploid human fibroblasts by means of a fluctuation analysis. cDNA was prepared from mutant HPRT mRNA and amplified by the polymerase chain reaction, and the sequence of the product was analyzed. Exon deletions, which very likely arose from mutations in the intron splice site consensus sequences, were found in 10 of the 37 mutants examined (27% of the total). Among the 28 mutations in the coding sequence, base pair substitutions predominated (89%). With the exception of one base pair involved in a tandem mutation, all base pair substitutions resulted in alterations in the predicted amino acid sequence of the protein. In addition there were three frameshift mutations, consisting of the deletion of one or two base pairs. Although mutations occurred throughout the coding sequence, 50% (14/28) were found in the 5' portion of exon 3. PMID- 1763388 TI - Localization of the gene encoding the alpha 2 subunit of the human VLA-2 receptor to chromosome 5q23-31. AB - The alpha 2 subunit of the VLA-2 receptor (CD49B) was mapped to human chromosome 5 by several independent approaches. First, the expression of the alpha 2 subunit at the protein level was investigated in a panel of human-mouse hybrid cell lines. Cell surface expression was detected by indirect immunofluorescence with monoclonal anti-alpha 2 antibody 12F1. Intracellular alpha 2 antigen was detected by immunostaining of whole cell extracts or of immunoprecipitated 12F1 antigen with the monoclonal antibodies 3H8 and 5C5. Second, the presence of human genomic alpha 2 sequences in the panel of human-mouse hybrids was detected by PCR, using primers derived from the published alpha 2 cDNA sequence. The specificity of the amplification product was shown by direct sequencing. The results of the PCR study were confirmed by amplifying a CD14 gene fragment, known to map to chromosome 5. Finally, in situ hybridization with a 3H-labeled 1040-bp cDNA probe, also obtained by PCR, confirmed and refined the localization of CD49B on chromosome 5 at q23-31. PMID- 1763389 TI - High-efficiency stable gene transfection using chloroquine-treated Chinese hamster ovary cells. AB - We describe a highly efficient stable gene transfection procedure for Chinese hamster ovary (CHO) cells using a modification of the calcium phosphate-DNA coprecipitation method. We have found that treatment of CHO cells with chloroquine increases the efficiency of gene transfer by up to 20-fold (from approx. 0.01% to approx. 0.2%) when transfection is done using the pSV2-neo plasmid. The optimized transfection procedure requires that CHO cells to be incubated with calcium phosphate-DNA coprecipitate and chloroquine (100 microM) for a total of 16 h. By using high-molecular-weight human genomic DNA as a DNA source for transfection, we show that this procedure is equally efficient for stably transferring a much larger gene, such as the 49-kb human hypoxanthine phosphoribosyltransferase gene. PMID- 1763390 TI - Enhancing peri-operative pain control. PMID- 1763391 TI - Aortobifemoral bypass for the critically ischaemic limb--is it worth while? AB - Little is written of the place of aortobifemoral bypass as a limb or below-knee level amputation stump salvage procedure in patients presenting with critical ischaemia with threat of limb loss. Over a 4-year period 151 patients referred to the Vascular Service of the University of Natal Hospitals with aorto-iliac occlusive disease and a threatened limb were studied. All were submitted to aortobifemoral bypass. Patients were divided into two subgroups: group 1 patients presented with rest pain or focal necrosis and were submitted to aortobifemoral bypass with concomitant digital or transmetatarsal amputation; and group 2 patients were submitted to a guillotine-type below-knee amputation in view of ascending infection or extended necrosis that made below-knee amputation impracticable. The objective was to obtain healing of the stump at the below-knee level. Early results within 1 month of operation were as follows: 5 patients (3.3%) died of myocardial infarction. There was no graft sepsis, and groin wound sepsis occurred in 7 (4.5%). Of the group 1 patients 8 required major amputation (8.2%). Three patients in group 2 required proximal above-knee revision (14.3%). The overall limb or stump salvage rate within 1 month of surgery was 89.4%. It was possible to follow up 105 patients in group 1 and 18 in group 2 for between 2 years and 5 years. In group 1, 2.9% required major proximal amputation and 3.8% a subsequent femoral-to-distal bypass. In group 2 none required subsequent major proximal amputation. Overall in those available for long-term follow-up 97% retained the use of a salvaged limb or stump.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763392 TI - Evaluation of a new hydrocolloid occlusive dressing for central catheters used in total parenteral nutrition. AB - Catheter-related sepsis still remains one of the most frequent and serious complication of total parenteral nutrition. Strategies for preventing contamination of central venous lines have focused on decreasing the number of micro-organisms around the exit site and inhibiting their entry into the catheter wound. This prospective study compares a new occlusive hydrocolloid dressing (Visiband; Convatec Squibb) with that of a polyurethane film dressing for nutritional catheters. Dressings were changed either on day 3 or day 5 after application. Swab smears of the catheter exit site at each dressing change were stained by Gram's method before inoculation onto a blood agar plate, a chocolate agar plate and a MacConkey agar plate. Significantly less colonisation occurred under the former dressing at day 3 and day 5 dressing changes. In addition, the polyurethane film dressing was associated with a significant increase in skin colonisation (P = 0.04) and the number of positive Gram-stain microbes if left unchanged for 5 days (P = 0.0018). Staphylococcus aureus catheter-related sepsis occurred in 1 patient on day 18 in the polyurethane film dressing group. In addition, Candida albicans colonisation was confined to patients with the polyurethane film dressing. While the type of dressing applied to the catheter exit site may influence the incidence of catheter colonisation and infection, it must be emphasised that strict adherence to aseptic technique during catheter insertion and manipulation of the dressing is vital in the prevention of catheter related sepsis during total parenteral nutrition. PMID- 1763393 TI - The Breast Clinic at Ga-Rankuwa Hospital/MEDUNSA. AB - The Breast Clinic at Ga-Rankuwa Hospital/MEDUNSA serves a large population of black South Africans. The patients present at a young age and commonly with very advanced disease. Problems in follow-up are more complex in this group because of difficulties with finance, transport and communication. The very large number of cases lost to follow-up and regular supervision after completion of treatment militates against collecting data for accurate reporting of results. An account is given of our experience in dealing with 532 cases of breast carcinoma seen over a period of 6 years. PMID- 1763394 TI - Foreign bodies in the gastro-intestinal tract. AB - Between 1971 and 1990, 70 patients with foreign bodies in the gastro-intestinal tract were admitted to our service. There were 35 children and 35 adults. Foreign bodies were found in the pharynx and the oesophagus in 22 patients, with 1 perforation; and in the stomach and intestines in 27, with 14 perforations. Fifteen foreign bodies were swallowed and defecated, 6 were inserted into the rectum. Coins were found in 8 patients, toys in 3, pins and needles in 6, chicken bones and fish bones in 15, and toothpicks, shaving blades, cutlery, dentures, plastic bag containing cocaine, parts of a foam rubber mattress and other items in the remainder. Foreign bodies retained in the oesophagus must be removed promptly lest obstruction and perforation occur. Many foreign bodies that have passed the oesophagus progress uneventfully to defaecation. Others become retained and should be removed. If retained in the stomach, endoscopic removal may be attempted before resorting to a laparotomy. Perforation is an urgent indication for operation. Those patients inclined to swallow foreign bodies intentionally and those who insert items into the rectum should undergo psychiatric evaluation. PMID- 1763395 TI - Trauma of the ureter. AB - Thirty-three ureteric injuries were treated over a 2-year period. The majority of patients presented late. The most common modes of repair were either ureteroneocystostomy or transuretero-ureterostomy. Complications were few and of little significance. PMID- 1763396 TI - An unusual thyroid cyst. A case report. AB - A solitary hydatid cyst in a 69-year-old woman presented as a cold area on thyroid scan. Clinically, it forms part of the differential diagnosis of neoplastic thyroid lesions. Surgery is effective for this uncommon thyroid cyst. PMID- 1763397 TI - Acute parapharyngeal space infections. A report of 12 cases. AB - Parapharyngeal space infections are a serious condition with a significant morbidity and mortality. Twelve cases seen between 1987 and 1990 are described. From the clinical findings it was clear that the tonsils appeared to be the most common source of infection and not other aetiological factors, such as dental and salivary gland pathology. Computed tomography was excellent in delineating the mass, but if this is not available ultrasonography appears to be of benefit. Intravenous antibiotics and the appropriate surgical intervention, when indicated, is the treatment of choice. An excellent clinical response was experienced; however, in 25% of patients recovery was complicated by aspiration pneumonia. PMID- 1763398 TI - Anal canal adenocarcinoma. A report of 4 cases. AB - Although rare, adenocarcinoma of the anal canal may be more common than previously thought in populations with a high incidence of peri-anal sepsis. Four such cases are presented and published reports reviewed. To avoid unnecessary delays in diagnosis, the clinician must adopt a high index of suspicion when dealing with chronic peri-anal disease. More regular follow-up examinations and biopsies of suspicious lesions are necessary. Since the origin and histological appearance of these tumours are often not clear cut, both clinician and pathologist must work closely together when correlating their findings. Until recently, the vast majority of cases have been managed surgically, and a concerted effort needs to be made to evaluate the role of chemoradiotherapy and preoperative radiotherapy as therapeutic modalities. PMID- 1763399 TI - Hemodynamic monitoring and pulse oximetry during percutaneous gastrostomy and jejunostomy: necessity or nuisance? AB - Hemoglobin desaturation and arrhythmias have been reported during diagnostic gastroscopy and colonoscopy. During endoscopic placement of percutaneous gastrostomy tubes (PEG), the gastroscope is inserted twice and the stomach is markedly distended, thus increasing the potential risk of complications. Also, the procedure is frequently performed in patients exhibiting underlying systemic disease or little respiratory reserve. Patients undergoing PEG or percutaneous endoscopic jejunostomy (PEJ) were studied prospectively. Blood pressure, pulse, pulse oximetry, and lead II ECG tracings were obtained. Measurements were made before sedation, after sedation, at gastroscope insertion, at gastrostomy placement, at gastroscope reinsertion, and at 5 min after the procedure. In all, 50 patients (mean age, 56.8 years; 16 women, 26 men) underwent PEG only (39 cases) or PEG/PEJ (11 cases). The endoscopy suite was the site for the procedure in 38 cases and the intensive care unit was used in 12 cases. The mean time required for PEG and PEG/PEJ was 14.7 +/- 1.1 and 18.9 +/- 2 min, respectively. Blood pressure remained stable throughout the procedure. Sinus tachycardia was observed in 72% of patients. Arterial oxygen saturation decreased after the administration of intravenous sedation but remained constant during the procedure. We reached the following conclusions: (1) desaturation occurs during sedation, (2) saturation remains constant during PEG/PEJ, (3) the mean blood pressure remains constant during PEG/PEJ, and (4) PEG/PEJ are safe procedures and monitoring should be individualized. PMID- 1763400 TI - Long-term efficacy of endoscopic papillo-sphincterotomy for common bile duct stones and benign papillary stenosis. AB - Since its introduction in 1974, endoscopic sphincterotomy (EST) for common bile duct stones and benign papillary stenosis has become a well-established therapeutic procedure; however, at present, its long-term efficacy in comparison with that of biliary tract surgery remains a matter of debate. The long-term results observed during our follow-up (4 +/- 2 years) were satisfactory, revealing the disappearance of or an improvement in symptoms in 85.6% of subjects who had undergone EST. Recurrent stones were documented in 10.2% of patients; EST related stenosis occurred in 3.8% of cases, approximately 3 times more frequently in papillary stenosis than in choledocholithiasis, likely due to the presence of a more extended incision in cases with common duct stones. A gallbladder in situ did not seem to be an additional risk factor after EST. As documented in other recent follow-up studies, the long-term efficacy of EST seems to be confirmed and comparable with that of biliary surgery. PMID- 1763401 TI - An appraisal of small and diminutive colonic polyps. AB - A retrospective review of all colonoscopic polypectomies performed in a busy surgical endoscopy unit over a 6-month period was undertaken. All patients were included who presented with colonic polyps measuring less than 1 cm in diameter for which sufficient specimens were available for histopathologic examination. In all, 262 were polyps removed from 206 patients; of these, 158 (60%) were neoplastic. There was a statistically significant predilection for polyps in the right colon to be neoplastic. Worrisome histologic patterns (severe dysplasia, carcinoma in situ, or invasive carcinoma) were seen in 18 specimens (6.5%). In two patients, polypoid carcinoma could be identified; in one case it involved a lesion measuring 0.2 cm in diameter. Since these lesions exhibit no distinctive gross features, only their endoscopic removal and histologic study can ensure proper diagnosis and treatment. PMID- 1763402 TI - Diagnosis of neuronal colonic dysplasia in primary chronic constipation and sigmoid diverticulosis endoscopic biopsy and enzyme-histochemical examination. AB - Neuronal colonic dysplasia is a separate clinical entity belonging to the group of congenital defects of intestinal innervation. Its enzyme-histochemical diagnosis is possible by endoscopic biopsy examination of the rectosigmoid. Enzyme-histochemically, it is characterized by dysplasia of the submucous plexus secondary to developmental defects. The principal clinical feature is weak propulsive motility. A clinical study was carried out to investigate the role of neuronal colonic dysplasia in the aetiology and pathogenesis of primary chronic constipation and diverticulosis of the sigmoid colon in adults. PMID- 1763403 TI - Real-time sonography of the mediastinum in adults: a study in 100 healthy volunteers. AB - Real-time sonography has proved to be a valuable tool in the evaluation of the mediastinum in children. In the literature there is a paucity of information on ultrasound examination of the mediastinum in adults. Using a 3.5-MHz sector scanner, we evaluated a new method for the examination of mediastinal organs in adults, which is practicable in routine as well as emergency diagnosis. The endpoints of this study were the visibility of mediastinal organs and the discomfort of the patient. In 100 healthy volunteers aged 20-40 years, the normal anatomy of the anterior and middle mediastinum was investigated. Neither the height nor the weight of the volunteers limited the examination. We found that this method causes no discomfort to the subject. Via the supra-, infra- and left parasternal approaches, anatomical structures of the mediastinum are visible in a high percentage of cases. To date, this method has proved its practicability in more than 250 patients suffering from blunt thoracic trauma, primary and metastatic tumours, and infections of the mediastinum. PMID- 1763404 TI - The role of fast neutrons in radiooncology--a critical appraisal. AB - The contribution of fast neutrons to local tumour control has been investigated worldwide since the mid-60's in more than 20 institutions. The high expectations anticipated from the promising results of experimental studies could not be adequately realized in the clinic. The late normal tissue damage was unacceptable due to poor depth dose characteristics and further technical limitations of the first generation low-energy machines. Even with sophisticated therapy planning systems and high-energy cyclotrons as well as comparable late normal tissue damage as witnessed after photons, only a few tumour entities have responded superiorly to fast neutrons. These particularly include macroscopic tumours of the salivary glands, prostate and, potentially, soft and osseous tissues. The role of fast neutrons for head and neck cancer has not yet been definitely proved. For bladder-, cervical- and rectal carcinomas, non-small cell lung-, pancreatic- and breast cancers as well as malignant gliomas, no therapeutic benefit as compared with photons was observed in the case of macroscopic residual or inoperable recurrent tumours. PMID- 1763406 TI - A prospective randomized study concerning to the point A dose in high-dose rate intracavitary radiation therapy for carcinoma of the uterine cervix. AB - From January 1983 through December 1987, a total of 138 patients with previously untreated carcinoma of the uterine cervix were entered into the prospective randomized study concerning the two different schedules of point A dose of remote afterloading high-dose rate intracavitary therapy (RALS) and external irradiation dose at the Center for Adult Diseases, Osaka. Group A consisted of 71 patients who were treated with fraction size of point A dose of 7.5 Gy and group B included 67 patients treated with fraction size of 6 Gy. According to the staging system of UICC (1978), 33 patients were classified into stage I, 50 patients stage II, 45 patients stage III, and ten patients stage IV. Three-year survival rates by stage and RALS schedule were in group A 80% and in group B 100% in stage I, 57% and 68% in stage II, 62% and 60% in stage III and 2/8 and 0/2 in stage IV. Survival curves showed no statistically significant difference in each stage. Late rectal and bladder complications requiring treatment (Kottmeier's grade 2 or more) after RALS developed 1.5% (2/138, group A none, group B two) and 1.5% (2/138, group A one, group B one), respectively. This result suggests that this trial is acceptable on survival as well as complication rates. PMID- 1763405 TI - [Simultaneous radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in advanced head and neck tumors]. AB - Between 1.1. 1987 and 31.12. 1988 47 patients with locally advanced head- and neck tumours (UICC-stage II: one patient, stage III: 16 patients, stage IV: 30 patients) were treated with simultaneous radio-chemotherapy. Localisations were hypopharynx (23 = 49%), oropharynx (16 = 34%) and other sites (8 = 17%). Radiation therapy consisted of 60 Gy (primary region, N+) or 50 Gy (N0) in daily fractions of 2 Gy each over six weeks. During week 1 and 5 of radiotherapy two courses of chemotherapy with 5-FU (600 mg/m2/day, i.v. continuous infusion for five days) and cis-platin (25 mg/m2/day i.v. bolus for five days) were administered. 43/47 patients (91%) responded to therapy. 34/47 (72%) patients achieved a complete remission, 9/47 (19%) a partial remission, and 4/47 (9%) no change. With a minimum follow-up of 26 months 17/47 patients (36%) are alive and NED, 4/47 (9%) are alive with tumour. 18 patients (38%) died of cancer, eight patients (17%) died of second tumours, intercurrent diseases and of unknown reasons. Actuarial four-year survival is 45% (stage III: 56%, stage IV: 42%), four-year NED survival is 35% (stage III: 68%, stage IV: 18%). There were no loco regional recurrences after additional surgical treatment of the primary and the neck following complete remission. In contrast after RCT alone and complete remission local recurrences in 6/21 patients (29%) and regional recurrences in 5/24 patients (21%) occurred. We conclude that simultaneous RCT is a new very effective treatment modality of locally advanced head and neck tumours producing superior loco-regional control compared to conventional management. PMID- 1763407 TI - Biological isoeffect distributions: consideration of the influence of dose per fraction and overall treatment time. A possible tool in future treatment planning. AB - The biological isoeffect distributions are calculated on the basis of the physical isodose distributions. They consider parameters of biological relevance such as the dose per fraction and the overall treatment time. A clinical example is presented to illustrate the method. The technique presented in this paper only requires minimal modifications in the conventional computer programs for treatment planning and can be updated very easily. The calculation of biological isoeffect distributions is a simple technique to facilitate the transfer of new radiobiological and clinical findings on alpha/beta ratios, tolerance doses and repopulation kinetics, into treatment planning. However, before they can be introduced into clinical practice, more reliable radiobiological data on normal tissues and tumours are required. PMID- 1763408 TI - [Effects of lonidamine alone or in combination with radiotherapy on survival and metabolism in human and rodent cell lines]. AB - In vitro investigations on the combined effect of radiation and Lonidamine in one human (LXI) and two rodent cell lines (3T3, V79) showed not a clear radiosensitizing effect. Especially no inhibiting influence on the repair of potentially lethal damage of V79 cells was found. Incubation at lower pH values (6.7 to 6.9) caused no increasing effects. Lonidamine induced damage on the mitochondrial dehydrogenase-system was quantitatively measured with a modified MTT-assay. PMID- 1763409 TI - [Effects of aphidicolin on cell recovery and repair of DNA damage in irradiated human fibroblasts]. AB - The effect of aphidicolin, a specific inhibitor of DNA polymerases alpha and delta, on recovery and repair of X-irradiated human fibroblasts was investigated. Aphidicolin concentrations from 0.5 to 5 micrograms/ml reduce DNA synthesis in exponentially growing cells after short incubation periods (1 h), longer incubation times (24 h) enhance this effect. Colony forming ability of unirradiated fibroblasts, treated in confluent growth state with aphidicolin, was not reduced. After incubation with aphidicolin contact-inhibited fibroblasts show reduced PLD recovery. For the short preincubation time (1 microgram/ml) the effect depends on aphidicolin concentration, for the long preincubation period the effect is independent of concentration. DNA double-strand break induction and rejoining was investigated after combined action of aphidicolin and X-rays using the neutral filter elution technique. The yield of initial DNA double-strand breaks was not affected by aphidicolin. After a 90-min recovery time, however, DNA double-strand break rejoining was markedly reduced. This effect was dependent on concentration for the short incubation time (1 h) but not for the long preincubation (24 h). PMID- 1763410 TI - Acute effects of T-2 toxin on radioactive iron incorporation into circulating erythrocytes in mice. AB - The 24-h and 72-h incorporation of 59Fe into circulating erythrocytes in mice were strongly inhibited by a single subcutaneous dose of T-2 toxin given 1 h before the radioisotope. The system is extremely sensitive, since a significant effect was detected with T-2 toxin doses as low as 0.30 mg/kg, which is about one tenth of the LD50 in the BALB/c strain used for the present study. In the treated animals no initial changes were observed in the blood 59Fe levels or in the rate of radioisotope clearance from plasma, indicating that the toxin does not interfere with iron absorption or transport. It is concluded that the inhibition observed reflects the damage produced by this toxin on reticulocytes and/or erythroblasts, and therefore this method could be of value as a very sensitive means of studying the risk of erythropoietic injury produced by dietary exposure to trichothecene mycotoxins. PMID- 1763411 TI - Effect of antioxidants on vanadate-induced toxicity towards isolated perfused rat livers. AB - The effect of trolox C, a water soluble vitamin E analogue, propyl gallate and ascorbate on vanadate hepatotoxicity was investigated in vitro. In isolated perfused livers from fasted rats, sodium orthovanadate (2 mmol/l) led to toxic responses including reduction of oxygen consumption, release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH)) and mitochondrial (glutamate-dehydrogenase (GLDH)) enzymes, intracellular accumulation of calcium, a marked depletion of glutathione (GSH) and an enhanced formation and release of thiobarbituric acid- (TBA) reactive material. Trolox C and propyl gallate inhibited the release of GPT and LDH partially and that of GLDH totally, but had no influence on vanadate-induced calcium accumulation or on the reduction of oxygen consumption. Both agents suppressed vanadate-induced lipid peroxidation (LPO) and partially prevented GSH depletion. Ascorbate failed to provide any protection probably due to the interference of its pro-oxidant potential with its antioxidant activity. The protection, mainly of mitochondria, afforded by those agents which also inhibited LPO substantiates our previous findings that the pro-oxidant activity of vanadate is mainly responsible for its direct hepatotoxic actions [2]. Besides, reduction of organ perfusion rate due to vasoconstriction also contributes to vanadate toxicity, but oxidative stress is not involved in this indirect toxic activity. PMID- 1763412 TI - Renal accumulation and urinary excretion of cisplatin in diabetic rats. AB - Previous work has demonstrated that cisplatin nephrotoxicity was attenuated in streptozotocin (STZ)-induced diabetic rats. The following studies investigated the hypothesis that renal cisplatin accumulation was reduced in diabetic rats. Male Fischer 344 (F344) rats were injected with 32 mg/kg STZ (i.p.) or citrate buffer. Renal platinum (Pt) accumulation was quantitated 0-96 h after the administration of 5 mg/kg cisplatin (i.p.) to normoglycemic and diabetic rats (greater than or equal to 4/group). Total renal Pt accumulation was decreased (P less than 0.05) in the diabetic rats, when compared to the normoglycemic group, 6 48 h after cisplatin injection. Further studies were also conducted to examine if urinary cisplatin excretion was enhanced in diabetic relative to normoglycemic groups. Urinary Pt excretion was quantitated 0-96 h following cisplatin (5 mg/kg, i.p.) administration. Pt excretion was increased in the diabetic group relative to the normoglycemics when comparisons were made on the basis of Pt excreted per hour or cumulative Pt excretion. Differences were also detected in urinary Pt concentration. The diabetic group had a lower urinary concentration of the metal 12-96 h after cisplatin injection. These findings suggest that the reduction in nephrotoxicity in diabetic rats may be at least partially due to decreased renal accumulation as well as altered renal excretion. PMID- 1763413 TI - Role of lipid peroxidation on renal dysfunction associated with glutathione depletion. Effects of vitamin E. AB - This study was designed to investigate the role of lipid peroxidation in the pathogenesis of renal dysfunction in glutathione (GSH)-depleted rats. Renal function parameters and acid-base status were analyzed in diethylmaleate (DEM) treated rats previously injected with vitamin E (Vit.E). Vit.E was effective in inhibiting the elevation in renal lipid peroxidation found in GSH-depleted rats. Vit.E also ameliorated the renal response to the metabolic acidosis without modification in lactate production induced by DEM administration. The increase in sodium and water urine excretion and the diminution of the urine to plasma osmolalities ratio were not reversed in these animals. These results lead us to conclude that lipid peroxidation is associated with distal acidification impairment observed with GSH-depletion, but it is not related to the sodium reabsorption alteration in the ascending loop of Henle. PMID- 1763414 TI - Effects of ozone on cellular ATP levels in rat and mouse alveolar macrophages. AB - Hydrogen peroxide (H2O2) is thought to be a major intermediate in the toxicity of ozone. In a previous study we demonstrated that ATP depletion may play an important role in the H2O2-induced inhibition of the phagocytic functions of alveolar macrophages. Ozone exposure can adversely affect the phagocytic capacities of alveolar macrophages. In the present study we investigated whether a decrease in the cellular ATP concentration may underly the effects of ozone on alveolar macrophages. Neither following single (6 and 12 h) exposure nor repeated (12 h/day for 3 and 7 days) exposures of mice or rats to 0.4 ppm ozone, were decreased levels of ATP found in the alveolar macrophages. In contrast, repeated exposures of mice for 7 days to ozone led to a significant increase (1.5-fold) in the ATP content of the alveolar macrophages. In vitro ozone exposure of rat and mouse alveolar macrophages also did not lead to a decrease in the cellular ATP concentration. These results showed that ATP depletion does not play a role in the toxicity mechanism of ozone for alveolar macrophages. PMID- 1763415 TI - Effects of aflatoxin B1 on myelopoiesis in vitro. AB - The short-term cultures of mouse myeloid progenitor cells for granulocytes and monocytes, granulocyte-monocyte colony-forming units (CFU-GM) (CFU-GM assay) and mouse long-term bone marrow culture (LTBMC) were used to investigate the hemopoietic suppression caused by aflatoxin B1 (AFB1). A dose-related suppression of granulopoiesis in short-term bone marrow cultures was seen when the cultures were treated with 10, 5, 1, 0.5 and 0.1 micrograms of AFB1/ml. Two selected doses of AFB1 (5 and 0.5 micrograms/ml) considered to be highly and slightly suppressive in CFU-GM assay exerted a strong suppression of myelopoiesis in LTBMC when applied long-term. Short-term (2 h) exposure of LTBMC to 5 micrograms of AFB1/ml caused a small damage to the myelopoiesis detected in the non-adherent layer. Short-term exposure to 0.5 micrograms AFB1/ml was without any effect on myelopoiesis in LTBMC. The production of colony-stimulating activity (CSA) by an adherent layer of LTBMC was decreased on the second and fifth day after the short term exposure to both doses of AFB1 and comparable with non-treated culture on the seventh day after the exposure. Presented results indicate that both short term culture of CFU-GM and LTBMC can be used in the definition and the prediction of host toxicity of AFB1 to hemopoiesis. However, comparing these two in vitro systems, the LTBMC appears to be more sensitive and discriminatory in an evaluation of hemopoietic toxicity. PMID- 1763416 TI - 1,1-Dichloroethylene hepatotoxicity: hypothyroidism decreases metabolism and covalent binding but not injury in the rat. AB - Our objective was to determine if the previously reported protective effect of hypothyroidism against 1,1-dichloroethylene hepatotoxicity was associated with a change in distribution and covalent binding. Sprague-Dawley male rats were made hypothyroid (HypoT) by surgical thyroidectomy 2 weeks prior to studies and compared to euthyroid (EuT) rats. Hypothyroidism decreased body weights and liver to body weight ratios while mitochondrial non-protein sulfhydryl groups and cytosolic alcohol dehydrogenase activities were increased by 50%. Rats received a single oral dose of 100 mg [14C]1,1-dichloroethylene (DCE)/kg in mineral oil and were killed at 2, 4, 12 or 24 h; controls received mineral oil only. More rapid liver injury, as measured by serum alanine aminotransferase activity and histology, was present at 2 and 4 h after DCE in HypoT than EuT rats, but a similar magnitude of injury was evident at 12 and 24 h. DCE decreased liver non protein sulfhydryl groups to a comparable extent in HypoT and EuT rats. Cytosolic glutathione S-transferase and alcohol dehydrogenase activities were decreased only in HypoT rats after DCE. HypoT rats excreted approximately 30% less total [14C]DCE-derived label in urine and their livers, kidneys and lungs consistently contained slightly less covalently bound [14C]DCE-derived label. In contrast, between 1 and 4 h after DCE, greater amounts of acid-soluble and acid precipitable [14C]DCE-derived label were recovered in red blood cells of HypoT rats. Our results indicate that hypothyroidism did not protect against oral DCE hepatotoxicity but was associated with a more rapid injury at early times. Concurrently, hypothyroidism was found to change the fate of [14C]DCE with higher amounts of 14C-label recovered at early times in red blood cells while less 14C label was excreted in urine and bound to liver. PMID- 1763417 TI - Effects of trichloroethylene on hepatic and splenic lymphocytotoxic activities in rodents. AB - The effects of trichloroethylene (TRI), a widely used industrial solvent, on various immunological and toxicological parameters have been examined in Sprague Dawley rats and B6C3F1 mice. Rats were administered TRI in vivo at 0.05, 0.5 and 5.0 mmol/kg per day intraperitoneally (i.p.) for 3 days. Mice were similarly treated with TRI at 10.0 mmol/kg. The highest TRI dose resulted in decreased splenocyte count and relative spleen weights, in rats and mice respectively and inhibition of hepatic natural killer cell (NK), natural cytotoxic cell (NC) and NPK cell (a newly described immune cell killing) activities in both rats and mice. High dose TRI in vitro resulted in minor decreases (less than 10%) in splenocyte viability, inhibition of LPS-stimulated mitogenesis in rat cells and marked inhibitions of NK and NC activities in all groups of effector cells. At the lowest in vitro dose mouse hepatic NK activity was still inhibited. Overall the data show that TRI is able to inhibit the activity of lymphocytotoxic cells which are involved in the immune surveillance of cancerous cells. This inhibition is particularly evident in the liver after in vivo administration and both liver and spleen cells after in vitro exposure. This suggests the possibility that compromised immune function may play a role in the carcinogenic responses in experimental animals on exposure to TRI. PMID- 1763419 TI - [Limitless]. PMID- 1763418 TI - Cardiotoxicity and cytotoxicity of the anthracycline analog 4'-deoxy-4'-iodo doxorubicin. AB - The cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4' deoxy-4'-iodo-DXR were evaluated and compared to DXR. A single dose of DXR 10 mg/kg i.v. in anesthetized rats induced a significant widening of S alpha T segment of the electrocardiogram, an increase in both mean arterial blood pressure and heart rate and a fall in systemic arterial dP/dtmax, while 4'-deoxy 4'-iodo-DXR 4 mg/kg i.v. induced a significant widening of S alpha T segment and an increase in mean arterial blood pressure. A chronic cardiomyopathy was induced over a 6-week period by three injections of DXR 3 mg/kg per week i.v. and was characterized by a progressive enlargement of S alpha T segment, a flattening of T wave, the occurrence of arrhythmias and histological alterations of myocardium. The contractile responses to adrenaline of isolated hearts from DXR-treated animals were significantly reduced compared to controls. 4'-Deoxy-4'-iodo-DXR (1.2 mg/kg per week three times) induced minor ECG alterations and sporadic episodes of arrhythmias. The contractile responses of isolated hearts were not significantly different from those of controls and microscopic examination of hearts revealed only minor changes. Cytotoxicity in vitro was evaluated by the colony formation assay; based on IC50, 4'-deoxy-4'-iodo-DXR was up to six times more cytotoxic than DXR on four human cancer cell lines. These results suggest that 4'-deoxy-4'-iodo-DXR is significantly less cardiotoxic and more cytotoxic than DXR. PMID- 1763420 TI - [Nursing home admission; a study among elderly applicants]. AB - This article describes the care needs, social network, housing conditions, utilization of care and diagnoses of 157 elderly applicants to nursing homes in Maastricht. The study was conducted during the period of February 1987 to July 1988. Possible differences in these characteristics in relation to the goal of the admission (rehabilitation versus continuous support) and in relation to prior living arrangements (home versus hospital) were investigated. In addition, the question to what extent substitution of care is possible is discussed. Within the group of nursing home applicants, a fairly clear distinction could be made between a number of subgroups, although care needs, social network (with the exception of the number of visits paid), and demographic characteristics showed no differences in relation to admission goals and prior living arrangements. The distinction was based particularly on the nature of the disorders (psychogeriatric versus somatic and chronic versus more or less acute), which was reflected not only in the main diagnosis itself, but also in differences in housing conditions, numbers of visits paid to others, and utilization of care prior to admission. Under the proposed policies for substitution, about a quarter of the applicants would be eligible for substitution. However, the major care needs, and the levels of formal and informal care prior to admission, as well as the shortage of alternative services, would seem to indicate that the actual possibilities for substitution are more limited. PMID- 1763421 TI - [Falling and getting up in a psychogeriatric nursing home. 2-year Incident Reports Resident Care]. AB - In 1988 and 1989 2880 incidents were reported in the psychogeriatric nursing home Stadzicht in Rotterdam. The incidents consist mainly of patient-falls (40%) or patients being found on the floor (29%). A patient falls approximately 2 times a year and is found on the floor approximately 1.5 times a year. Male patients ran a greater risk of falling than female patients. The incidents occur especially during the daytime in the living room or the hall. In 41 (2%) incidents the consequences for the patient are serious, including 28 hipfractures. Intrinsic factors (such as gender) are more important risk factors for falling than extrinsic factors (environment or the use of physical restraints). Several risks are therefore inevitable. The extrinsic factors are most suitable for prevention in the short run. Furthermore, it is necessary to asses patients on admission in terms of proneness to falls. PMID- 1763422 TI - [Faces get names--cognitive training for psychogeriatric patients for remembering names and faces]. AB - By systematic training, 14 psychogeriatric patients (aged 70 to 95 years and admitted to day care because of dementia) were taught the first names of 8 members of staff of the day care center. Treatment duration was one month, twice weekly. The therapist introduced the names by a step-by-step approach, beginning with two name-face combinations, and adding one new name (and photograph of that person's face) every next training session. Treatment consisted of a combination of several cognitive strategies: organisation and directed attention, rehearsal, first letter cueing and vanishing cue techniques, and paired-associate learning based on rhymes, pictures and visual imagery. Patients were assigned at random to a treatment and a control group (waiting list condition). Patients in the control group received their training after the waiting period of one month. Using this pretest-posttest-control-group design, we were able to objectively evaluate treatment effects. Treatment caused a significant enhancement of knowledge of staff members names. Gains achieved using this program persisted over at least one month, as could be demonstrated by a follow-up evaluation. PMID- 1763423 TI - [Validity of a new psychogeriatric behavior observation scale for application in nursing homes and homes for the aged]. AB - In this article we report a study on the validity and discriminating power of the behaviour rating scale OPG - 'Observation Psycho Geriatrics'. The OPG was designed to measure the need of care and the remaining capacities of people with a mild dementia syndrome. To establish the external validity in nursing homes, the OPG was compared with the BOP (Dutch version of the Stockton Geriatric Rating Scale) for 74 residents and in homes for the aged with the BPS, a rating scale for mental and social problems (66 residents). Both scales show a substantial relationship with the OPG and confirm its validity. Assumptions concerning OPG scales were given for six different levels of residential care (829 residents). The 7 distinguished OPG-scales show differences in mean scores, which are in general plausible in the light of these assumptions. The mean scores for residents in homes for the aged who receive special treatment are best comparable with those of average nursing home residents. PMID- 1763424 TI - His and hers recombinational hotspots. PMID- 1763425 TI - Vertebrate development: an emerging synthesis. PMID- 1763426 TI - From linked marker to gene. AB - An area of increasing importance in human genetics research is the strategy of 'reverse genetics' or 'positional cloning', whereby a gene associated with a genetic disease is isolated on the basis of its approximate chromosomal position. This article and the accompanying centrepage diagram describe the main features of this strategy and outline the techniques involved; they are designed to be used for teaching purposes and as a general reference for those from other fields of genetics research. PMID- 1763427 TI - Genetically identified protein kinases in yeast. II: DNA metabolism and meiosis. AB - Genetic analysis of protein kinases in Saccharomyces cerevisiae has revealed protein phosphorylation as a key regulatory mechanism both in the mitotic cell cycle and in meiosis. This article reviews genetically identified protein kinases that are associated with DNA metabolism and the meiotic pathway. PMID- 1763428 TI - Molecular analysis of male gametogenesis in plants. AB - Reproduction in plants rivals the complexity of the process in animals. Recently, several genes that are expressed at specific stages during male gametogenesis have been cloned. These anther-specific genes are providing tools with which to study the cis- and trans-acting factors that regulate gene expression during pollen formation. Sequence analysis of the coding regions of some of these abundantly expressed anther genes is providing unexpected insights into the cell cell interactions occurring during gamete formation and fertilization. PMID- 1763429 TI - 5-HT advances on four fronts. PMID- 1763430 TI - Nuclear magnetic resonance and differential scanning calorimetry as tools for studying drug-membrane interactions. PMID- 1763431 TI - Chaos and illusion. AB - Pharmacology is the study of the interaction of drugs with living organisms, especially humans. The body is a very complicated system, which suggests that the 'effect' induced by a drug is not a single entity but a change in several variables at the same time, all of which are interrelated in a nonlinear fashion. Research on nonlinear systems in other fields of science--commonly known as chaos theory--may therefore be of use in understanding pharmacology, as explained here by J. M. van Rossum and J. E. G. M. de Bie. They argue that in the study of drug effects, several variables should be measured simultaneously. Many pharmacologists prefer to construct an illusion of reality, studying just one of the essential variables and averaging data in a population of subjects, thus losing the opportunity to understand what a drug really does to a patient. PMID- 1763432 TI - Amyloid deposition as the central event in the aetiology of Alzheimer's disease. AB - While there may be many causes of Alzheimer's disease (AD), the same pathological sequence of events, described here by John Hardy and David Allsop, is likely to occur in all cases. The recent discovery of a pathogenic mutation in the beta amyloid precursor protein (APP) gene on chromosome 21 suggests that APP Mismetabolism and beta-amyloid deposition are the primary events in the disease process. The occurrence of AD in Down syndrome is consistent with this hypothesis. The pathological cascade for the disease process is most likely to be: beta-amyloid deposition----tau phosphorylation and tangle formation--- neuronal death. The development of a biochemical understanding of this pathological cascade will facilitate rational design of drugs to intervene in this process. PMID- 1763433 TI - Epidemiological observations on helminth infections of calves in southern Ghana. AB - This paper describes helminth infections in three groups of calves of different ages grazing naturally infested pastures from March 1987 to May 1988. Calves in which the faecal egg output was followed from birth showed Toxocara vitulorum eggs as early as two days after birth and maximum patency occurred after two months. The fall in Toxocara egg output coincided with a rise in that of the strongylates; Haemonchus spp., Trichostrongylus spp. and Oesophagostumum spp. The influence of rainfall in dictating strongylate nematode infection was clear with high egg output during high rainfall and low egg counts when the rainfall was lower. There was an indication that calves carry the infection from the end of the minor rainy season in November to the beginning of the next rains in March and then contribute to pasture contamination. However, calves born in December may remain uninfected until the onset of the rains. PMID- 1763434 TI - Porcine trypanosomosis in Nigeria: infections in local and exotic pigs in the Nsukka area of Anambra State. AB - A twelve-month survey in three Local Government Areas (LGA) in Nsukka zone, Anambra State, Nigeria revealed that out of 150 local and exotic breeds of pig examined, 46 (30.7%) were infected with trypanosomes. Both single and mixed infections of Trypanosoma brucei and T. congolense were observed. However, T. brucei was the predominant trypanosome encountered. The husbandry system in practice was the most significant factor influencing the prevalence of trypanosomes in the pigs. In addition significantly higher prevalences were recorded during the rainy seasons. Clinical trypanosomosis was encountered in only eight of the 46 positive cases seen, with anaemia, loss of weight and anoestrus being the most important effects associated with these infections. The pathogenic and economic significance of these findings are discussed. PMID- 1763435 TI - Economic value of urea-treated straw fed to lactating buffaloes during the dry season in Nepal. AB - An experiment was conducted to study the effects of feeding urea-treated rice straw to lactating buffaloes in the Koshi Hills. Six pairs of similar buffaloes on farms were selected. All were given a conventional diet based on rice straw for four weeks, then one of each pair was given 15 to 20 kg/day of urea-treated rice straw for a period of four weeks while the control group received untreated rice straw. In the final four week period all animals were given the conventional diet. Feeding straw treated with 4% urea increased the voluntary intake of straw by 25% and increased milk yield by 1.6 litres/day compared with buffaloes fed the conventional diet containing untreated straw. Milk production remained elevated after the four-week treatment period had finished. The results show that buffalo cows fed urea-treated straw achieved better weight gain, and milk yield increased significantly (P less than 0.01) compared with the control animals. During the treatment period the net benefit was 4.0 (i.e. US$1.16) Nepalese currency rupees (NCRs) per day and the incremental rate of return was 46 per cent. Moreover, in the four weeks following the treatment period the net benefit was 10.0 NCRs (i.e. US$0.40) per day. Ensiling rice straw with 4% urea can be recommended as a safe, economical and suitable method for improving the nutritional value of rice straw on small farms in Nepal thus increasing milk production and liveweight of lactating buffaloes. The practice of feeding urea-treated straw is economic for farmers during the dry season from January to April.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763436 TI - Bordetella bronchiseptica from aborted equine foetus. PMID- 1763437 TI - Prevalence of bovine campylobacteriosis in indigenous cattle of three states in Nigeria. AB - A survey of bovine campylobacteriosis in breeding bulls and cows was carried out in the states of Kaduna, Kano and Borno. Six hundred and eighty nine cattle composed of 585 and 104 breeding bulls and cows respectively were sampled. Campylobacter fetus subsp. venerealis was isolated from 12 bulls while Campylobacter fetus subsp. fetus was isolated from three of them. Campylobacter fetus subsp. fetus was isolated from four cows while Campylobacter fetus subsp. veneralis was isolated from one cow. The overall prevalence of campylobacteriosis in the three states was 2.9% (20/689). The result of the study identifies Campylobacter fetus subsp. venerealis as the agent of enzootic infertility in Nigeria and suggests that it may be a significant problem. PMID- 1763438 TI - Communal farmers and tick control--a field study in Zimbabwe. AB - Intensive dipping of cattle to control ticks and tick-borne diseases precludes development of endemic stability to the latter. Alternative control strategies have been recommended which reduce the frequency of dipping and permit the expression of tick resistance and endemic stability. However, such strategies imply acceptance by cattle owners of higher tick burdens. In this study the views of a group of communal farmers to tick control are described and the impact of these views upon adoption of other strategies is discussed. PMID- 1763439 TI - Distribution of Boophilus species ticks in Swaziland. AB - Recent outbreaks of bovine babesiosis caused by Babesia bovis in Swaziland had indicated the presence of the vector tick Boophilus microplus in the country although it had never before been directly identified. Engorged female Boophilus ticks were collected from cattle at diptanks in the course of a tick resistance survey and used to map the distribution of the two different species of Boophilus. B. decoloratus was found to be widespread throughout the country. B. microplus was identified for the first time in Swaziland and was found to have a patchy distribution. The implications of these findings are discussed. PMID- 1763440 TI - Copper deficiency in ruminants in the Rift Valley of East Africa. AB - Enzootic ataxia of newborn domestic ruminants and particularly of small ruminants is a widespread disease often observed in East Africa. It is characterised by very low blood copper levels and sometimes by histological lesions characteristic of a severe copper deficiency. This disease observed and described by various authors in Kenya, Ethiopia and Djibouti seems to be closely associated with the pedogeological area of the Rift Valley. Climatic conditions and geo-morphological characteristics of this area, particularly the molybdenum and sulphur excess in this volcanic region, seem to account for the marked clinical signs of this mineral deficiency. PMID- 1763441 TI - Analyses of baseline survey data on rinderpest in Bahr el Ghazal Province, with proposal of an improved vaccination strategy against rinderpest for southern Sudan. AB - Results from analyses of baseline surveillance data on rinderpest are used for proposing an improved vaccination strategy against rinderpest in southern Sudan. Sera from 4,074 (47%) of the total sample of 8,565 cattle collected in a series of cross-sectional surveys in 400 cattle camps in the Bahr el Ghazal Province of southern Sudan were tested for rinderpest antibodies using the standard virus neutralisation test (VNT) technique: 77.4% were positive while 22.6% gave negative results. The data were cross-classified according to five variables: herd management, breed, age, sex and geographic region (grazing location). The percentage antibody-positivity level (taken as an approximation of past experience with rinderpest antigen and the corresponding prevalence ratio estimates of relative risk) for each variable are discussed within the context of the known characteristics of immunity to rinderpest in endemic areas and the husbandry practices of the cattle owners in the study area. Results suggest that rinderpest "hot-spots" of transmission and/or low level of herd immunity should be mapped out for concentrated efforts to vaccinate calves and young adults so that the high level of antibody-positivity observed in this study can be maintained and transmission permanently interrupted. PMID- 1763442 TI - [Use of fluorescence methods in glaucoma]. PMID- 1763443 TI - [Postradiation secondary glaucoma and prevention measures]. AB - The authors have examined the possibility of preventing the development of secondary glaucoma after eye irradiation with a narrow medicinal proton beam. Twenty-eight patients with cilio-choroidal melanoma were involved in the study, 7 male and 21 female ones, aged 48.4 on an average. The authors' findings evidence that postradiation changes in the anterior segment of the eye, resulting from radiation iridocyclitis, are mainly responsible for the development of secondary glaucoma. Preliminary laser-effected formation of iridal coloboma is conducive to a normal flow in the anterior chamber at the expense of an additional pupil functioning and thus helps reduce the possibility of secondary glaucoma development by 1.6 times (or by 38.5%). PMID- 1763444 TI - [Intraoperative diagnosis in removal of foreign bodies from the eye]. AB - The efficacy of intraoperative application of a complex of diagnostic clinical and instrumental methods, including gonioscopy, biomicroscopy, ophthalmoscopy, electron location, transillumination, ultrasonic location, and acoustic scanning, has been demonstrated in surgeries for removal of foreign bodies from the eyes of 548 patients. Clinical variants of the fragment site and the aggravating factors were defined, as were the informative value of each of the afore-said methods for each of these clinical variants. PMID- 1763445 TI - [Late results of cosmetic prosthesis in patients with anophthalmia syndrome]. PMID- 1763446 TI - [Possibilities of reflexotherapy in the treatment of post-traumatic eye complications]. AB - Reflex therapy was used in the treatment of 448 patients with various post traumatic conditions of the eye and its appendages. Both routine methods and the methods developed by the author were employed. Good results were achieved in the majority of cases. For the first time visual function was improved in the patients with optic nerve atrophy. PMID- 1763447 TI - [Use of quantum hemotherapy in multimodal treatment of uveitis]. AB - The results of recurrent uveitis treatment in two groups of patients are analyzed. Group I patients were administered drug therapy, in Group 2 it was combined with auto-transfusion of UV-irradiated blood. Autotransfusion had a good effect on the general status of the patients, on the clinical course of the disease, and on some hemogram and immunity parameters. This permits a conclusion on the usefulness of adding quantum hemotherapy to the therapeutic complex for patients with uveitis. PMID- 1763449 TI - [Radial asymmetric keratotomy in mild-degree myopia]. AB - The suggested method for surgical correction of weak myopia involves two mutually perpendicular incision on the cornea in the major meridians. These two incisions result in but a slight alteration of the tissues, and a stable refraction effect of about 1.5 diopters is achieved at once; vision acuity improves to make 0.9 1.0. PMID- 1763448 TI - [Copper metabolism in scleral tissue and possibilities of its correction in myopia]. AB - Copper measurements in scleral tissue of 14 cadaveric emmetropic eyes and in 10 eyes with myopia of various degrees have shown a significant reduction of these levels in the equatorial and posterior segments of myopic sclera and abnormal distribution of copper in the tissue, this indicating disordered metabolism of this trace element. A method for drug correction of the detected disorder has been experimentally tried, consisting in administration under the Tenon's capsule of a copper coordination compound on a foam composition base, used for sclera fortifying injections in progressive myopia. This resulted in elevation of scleral copper concentration, activization of collagen biosynthesis processes, and improvement of scleral tissue elasticity. PMID- 1763450 TI - [Iridoangiography using indocyanine green in severely pigmented iris in clinical conditions]. AB - The authors presented the results of iridoangiography. In the course of the studies it was established that infrared light is tolerated easier than the blue one in fluorescent iridoangiography. This technique is of interest for the study of microcirculation in the vessels of the iris of the eye in inflammatory and dystrophic processes. PMID- 1763451 TI - [Indocyanine green fluorescence iridoangiography in pigmented iris]. AB - Indocyanine green (ICG) fluorescent iridoangiography was used to diagnose pigmented tumors of the iris. Ten patients with pigmented tumors of the iris were examined using a modified photo-slit lamp with infrared narrow-strip optic filters. Fluorescein fluorescent iridoangiography was found ineffective. ICG fluorescent iridoangiograms have shown the vascular net and helped define the time parameters. Signs characteristic of the studied condition were defined. ICG fluorescent iridoangiography, biomicroscopy, and clinical data helped specify the diagnosis, this permitting the choice of the correct treatment strategy. PMID- 1763452 TI - [Use of distant thermography in uveitis in children]. AB - Forty-four children aged 6 months to 14 years, suffering from endogenous uveitis of various sites were examined at different phases of the diseases by a scanning type apparatus, AGA-780M-thermographer (Sweden). The results permit a conclusion that long-distance thermography may be effectively used to assess the ocular status even in small restless children. Uveitis active phase was found associated with a hyperthermal reaction in all the examined sites. Hyperthermia was found related to uveitis localization. The authors suggest that thermoasymmetry parameters and the corneolimbic gradient be used as additional objective criteria for the assessment of uveitis activity and dissemination in children. PMID- 1763453 TI - [A new method of drug administration into the posterior section of the sub Tenon's space]. AB - A new method for instillation and deposition of drugs in the sub-Tenon's space has been developed, that permits the maintenance of a high concentration of the drug directly in contact with the posterior segment sclera and membranes of the optic nerve anterior segment. It consists in the following: a collagen hemostatic sponge, connected to a silicone tube, is implanted into the sub-Tenon's space; the drugs are administered via this tube. Analysis of the results of 115 surgeries has demonstrated considerable advantages of this method over the traditional methods of drug instillation. PMID- 1763454 TI - [Planning of ophthalmologic research in the 11th 5-year period according to the branch fund of research activities]. PMID- 1763455 TI - [Use of T-activin and thymalin in the treatment of ophthalmic herpes]. AB - Therapeutic efficacies of thymalin and T-activin were assessed in 80 patients with ophthalmic herpes. Thymic hormone preparations are recommended for the treatment of a protracted condition. To monitor the course of immunomodulating therapy, the neutrophil injury index and measurements of secretory IgA in the lacrimal fluid may be used, besides the routine tests. PMID- 1763456 TI - [Ocular drug films: problems and perspectives]. AB - Fifteen such films created at two Moscow Institutes were allowed for use after clinical trials by the Pharmacologic Committee of the USSR Ministry of Health. Two principal advantages of ocular medicinal films as against ocular drops and ointments are prolonged action of the drugs and accurate dosage of the drug. Application of films may replace subconjunctival instillations in a number of cases. The film completely dissolves in the conjunctival sac, thus providing the daily dose of the drug. Therefore the film may be applied once a day and only in grave cases twice. A packed film retains its activity and sterility for 12-14 months. Unfortunately commercial films do not always meet the medicinal requirements. Noteworthy that individual intolerance of some film brands varies within 0.1 to 8.03%, and that there are certain contraindications against the use of these films. Ocular medicinal films is an intensive care dosage form that may be manipulated only by specially trained personnel. Of course the films cannot absolutely replace other forms of drug administration. Further research is necessary, aimed at improvement of the tolerance of films, creation of films for children, and commercial manufacture of the drugs that were found the most effective and were best of all tolerated, as well at training of personnel. PMID- 1763457 TI - [A device to determine sensitivity to glare]. PMID- 1763458 TI - [Effects of laser fragmentation of the lens mass on ocular tissues in experimental animals]. AB - Side effects of laser on the posterior corneal epithelium and the retina during intracapsular YAG laser fragmentation of transparent lens fibers in various modes of laser operation were experimentally studied. The pulse power varied from 3 to 7.7 mJ, number of pulses from 55 to 160, length of exposure 10(-8) sec, diameter of the spot in the focus 30 microns. Animal eyes were enucleated on days 3-6 after the procedure. Posterior corneal epithelium was examined in the Hitachi scanning electron microscope, the retina in a light microscope. The findings evidence that injury to the posterior corneal epithelium in intracapsular YAG laser fragmentation of the lens depends mostly on the number of pulses and not on the exposure energy. A safe number of coagulates should not surpass 100, this being quite sufficient for fragmentation of the lens fibers at exposure power of 5-6 mJ. Such operation mode is safe for the retina as well, this recommending it for clinical use. PMID- 1763459 TI - [Ocular morbidity in Palestine]. AB - Examinations of 1427 subjects (2848 eyes) on the Western Bank of the Jordan and in the Ghaza sector have revealed a high incidence of ophthalmic diseases, particularly of conjunctivitis, cataracts (nuclear among other ones), corneal opacities, pigmented retinal dystrophies, diabetic retinopathies, congenital conditions. Blindness resulted mostly from corneal opacities, most often developing after trachoma, and from congenital diseases of the eyes. Marriages between relatives appear to play an essential role in the development of congenital diseases of the eyes, as well as of pigmented abiotrophy of the retina. PMID- 1763460 TI - [A case of correction of weak vision by means of a system involving a dispersing intraocular lens]. PMID- 1763461 TI - [Use of magnifiers in poor eyesight (literature review)]. PMID- 1763462 TI - [Modification of sinusotomy]. AB - Sinusotomy modification, developed by the authors, consists in combination of traditional subscleral surgery with posterior cyclo-retraction and the formation of an uveal pouch. This technique was used in the treatment of 28 patients (28 eyes) with primary open-angle glaucoma. Immediate hypotensive effect was achieved in all the patients (in one case surgery was paralleled by pilocarpine instillations). Twenty-four patients were examined in late periods (up to 1 year) after surgery. Ophthalmic tone normalization was achieved in 91.7% of cases (in 83.3% of cases no drug instillations were used). Vision acuity and visual field were unchanged or improved in 87.5 and 95.8% of cases, respectively. No grave complications were recorded. PMID- 1763464 TI - Change and challenges for the SVS. PMID- 1763463 TI - [Dosed drainage in the surgical treatment of post-traumatic glaucoma in children]. AB - The authors have developed an operation involving artificial drainage system implantation to children with secondary posttraumatic glaucoma. The drainage system represents a silicon cylinder 2 mm long with an external diameter of 2 mm and internal diameter of 1.5 mm. A thin membrane attached to the internal walls of the cylinder along 1/3 of the diameter, free otherwise, is situated in the middle of the cylinder. There are small openings, directed to opposite sides, in the terminal sections of this membrane. Such surgery was carried out in 18 eyes of 18 children aged 5 to 14 with secondary posttraumatic glaucoma. The patients were discharged from hospital on days 7-10 after surgery with ophthalmic tone of 17 to 21 mm Hg. A follow-up of up to 1.5 years has shown that the ocular pressure was normal (17-22 mm Hg) in 13 eyes, slightly higher in 4 (23-26 mm Hg), and high (35 mm Hg) in 1. Repeated surgery of this patient with revision of the intervention site has revealed that the distal end of the drainage tube was closed with solid connective tissue. This complication was due to a technological error in the course of operation. PMID- 1763465 TI - Tuberculosis and badgers. PMID- 1763466 TI - Epidemiology of Salmonella typhimurium infection in calves: persistence of salmonellae on calf units. AB - Salmonella typhimurium DT204C infection is the commonest cause of salmonellosis in calves. On five calf rearing farms a distinct strain, as indicated by plasmid profile analysis, was found to have persisted on the premises for periods ranging from four months to two years, the average being 14 months. The persistence of salmonellae in the environment appears to be an important factor in the epidemiology of calf salmonellosis and clearly indicates the inadequacy of many cleaning and disinfection routines. PMID- 1763467 TI - A radiographic method for measuring the effect of exogenous hormone therapy on uterine involution in ewes. AB - Twenty-six pluriparous Suffolk ewes were used to monitor the effects of four hormone treatments on the rate of uterine involution, which was assessed by means of radio-opaque markers and radiography. The close correlation between measurements of the genital tract in live sheep and after slaughter indicated that this method of monitoring uterine involution was acceptably accurate. Uterine involution was complete by about 29 days after lambing. None of the hormone treatments with progesterone, oestradiol-17 beta, prostaglandin F2 alpha or an oxytocin analogue, administered shortly after lambing, had any effects on the rate of uterine involution. There was no correlation between the duration of increased plasma concentrations of 13.14 dihydro-15-keto-prostaglandin F2 (PGFM) and the rate of uterine involution. PMID- 1763468 TI - Preliminary observations on reproduction in a female sheep-goat chimaera. AB - Four oestrous cycles of a female sheep-goat chimaera were monitored by using a vasectomised ram. The mean (+/- se) length of the cycle was 18.5 +/- 0.64 days with a range from 17 to 20 days. The chimaera was superovulated twice, bred to fertile rams, and the embryos recovered by laparotomy 13 or five days after oestrus, so that karyotype analysis could reveal the genotype of the oocyte. After the first superovulation one ovine day-13 embryo was collected; two fragments of another embryo (or embryos) were also collected, but readable chromosome spreads were not obtained from these embryos or from the two four-cell embryos that were collected five days after the second superovulation. Two surgical embryo transfers to the chimaera resulted in pregnancies. The first transfer involved an eight-cell ovine embryo and two caprine morulae and ended in the abortion of an ovine fetus between days 110 and 130. The second pregnancy occurred after the transfer of two ovine and two caprine morulae. A healthy lamb was born on day 147 of pregnancy. Both placentae had small numbers of cotyledons. A histological evaluation of the cotyledons revealed an abnormal placentome structure in the first pregnancy but not in the second. PMID- 1763469 TI - An electrocardiographic survey of cardiac rhythm in Irish wolfhounds. PMID- 1763470 TI - Morbillivirus infection in Mediterranean striped dolphins (Stenella coeruleoalba). PMID- 1763471 TI - Continued susceptibility of Ostertagia ostertagi infective larvae to morantel tartrate. PMID- 1763472 TI - Embryo transfer: putting welfare first. PMID- 1763473 TI - Bordetella bronchiseptica in a closed cat colony. PMID- 1763474 TI - Anthelmintic resistance. PMID- 1763475 TI - Integrated strategy to control East Coast fever. PMID- 1763476 TI - Atypical M avium induced tubercular lesions in pigs. PMID- 1763477 TI - Medetomidine in horses. PMID- 1763478 TI - Trypanosomiasis in different breeds of cattle from Benin. AB - Blood of different breeds of cattle, namely Lagune from the Atlantic province, Borgou and Borgou x Zebu from the Borgou province, and Somba and Zebu from the Atacora province of Benin, were examined for trypanosome infection. Thick and thin blood smears for trypanosomes, the card agglutination test (CATT), indirect immunofluorescent antibody test (IFAT) and trypanolytic test for antibodies to trypanosomes were used. Trypanosomes were detected in 19.3% (range 9.8-31.4%) of animals by examination of blood smears; antibodies to trypanosomes were found in 89.8% (range 88.4-100%) of samples by IFAT, 50.6% (range 34-87.5%) by CATT and 3.4% (range 1.1-7.1%) by trypanolytic test. Trypanosoma vivax and Trypanosoma congolense were the main species in Benin with a low number of Trypanosoma brucei. Zebu had lower infection rates than trypanotolerant breeds of Benin. The infection rates of various trypanotolerant breeds were not significantly different. PMID- 1763479 TI - Identification of sylvatic Trichinella (T3) in foxes from France. AB - Thirty-three foxes (Vulpes vulpes) from a sample of 1912 collected in France were found to be infected with Trichinella spp. Four isolates were obtained for genetic identification. Isoenzymatic and biological analysis of these isolates revealed the presence of two distinct genetic types of Trichinella, Trichinella spiralis s.str. (T1) and Trichinella sp. (T3) (Trichinella nelsoni according to Soviet authors) in the fox population. The reproductive capacity index of these isolates in Wistar rats was high for T. spiralis and low for T3. This is the first report of T3 type from wild animals in France. The epidemiological implications are discussed. PMID- 1763480 TI - Experimental Trichinella spiralis infection in sheep. AB - During susceptibility studies of non-specific hosts, three merino sheep were infected with 3000, 5000 or 7000 Trichinella spiralis larvae by gavage. Clinical, physiological and serological parameters were assessed during the experiment. On the 152nd day p.i., animals were necropsied and, using artificial digestion methods, numbers of Trichinella larvae in muscle tissues were determined. The most infected parts were masseters with 3122 larvae g-1 muscle, 5526 larvae g-1 muscle and 4058 larvae g-1 muscle and diaphragms with 2778 larvae g-1 muscle, 2725 larvae g-1 muscle and 2320 larvae g-1 muscle, for the 3000, 5000 and 7000 infection levels, respectively. A positive correlation between infective rate and circulating antibodies was observed using ELISA and latex agglutination (LA) test methods. Trichinella larvae from sheep applied by gavage to ICR mice developed to the muscle stage. No significant changes were found in the clinical and physiological parameters of infected animals. Our results confirm the high susceptibility of merino sheep to T. spiralis infection. PMID- 1763481 TI - Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs. AB - Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials. PMID- 1763482 TI - Antigen-specific lymphocyte proliferative responses in vaccinated and Hypoderma lineatum-infested calves. AB - Cattle infested with the common cattle grub, Hypoderma lineatum (Villers) develop specific humoral antibodies and a cellular immune reaction, defined by delayed type hypersensitivity, to purified H. lineatum proteins. This investigation was designed to study the antigen-specific bovine lymphocyte response to hypodermin A (HyA), a serine protease of larval first-instar H. lineatum. Calves were vaccinated with either native or denatured HyA, and challenge-infested with H. lineatum. The kinetic development of a cellular immune response to HyA was monitored during vaccination and infestation. The HyA-specific responses were highly variable and weak during vaccination and infestation. Although HyA specific lymphocyte blastogenic responses were observed, no correlation was noted between the magnitude of antigen-specific, peripheral lymphocyte proliferation and larval mortality. In striking contrast to responses observed during infestation, intense HyA-specific lymphocyte responses were observed with 3 calves 6 months after recovery from infestation. In addition, those responses were further heightened by a 250 micrograms booster injection of pure HyA. PMID- 1763483 TI - Survey of Eimeria spp. oocysts in feces from Louisiana State University ewes. AB - The prevalence and identification of Eimeria spp. in the Louisiana State University ewe flock were determined from 109 fecal samples. Unsporulated oocysts were recovered from 94 of the samples and 1208 oocysts representing ten species of Eimeria were identified: E. ahsata, E. crandallis, E. Faurei, E. granulosa, E. intricata, E. ovina, E. ovinoidalis, E. pallida, E. parava and E. punctata. Eimeria ovinoidalis, which is probably the most pathogenic, was the species common to the most number of samples (59.6%); however, E. granulosa, which is non pathogenic, was the most numerous species (23.7% of the total identified). The prevalence and identification of oocysts from ewes may be useful to evaluate infection potential when considering control programs, especially for lambs. PMID- 1763484 TI - Prevalence of Sarcocystis in domestic pigs in India. AB - Muscle samples from 890 slaughtered pigs were examined for the presence of sarcocysts. A high prevalence rate of 67.98% was observed. Two types of microsarcocysts were recorded. The sarcocyst wall of one type had redial striations and the other possessed hair-like villar protrusions. The species were identified as Sarcocystis miescheriana and Sarcocystis suihominis; there was a slightly higher incidence of the latter species (47.11%) than of the former (43.14%). S. suihominis has been identified for the first time from pigs in India. PMID- 1763485 TI - Effect of temperature on transtadial transmission of Theileria annulata in Hyalomma anatolicum anatolicum ticks. AB - The effect of temperature on the transtadial transmission of Theileria annulata in Hyalomma anatolicum anatolicum was studied. Variation in temperature (4-40 degrees C) had a significant effect on moulting rate of the ticks and transmission of theilerial parasites from nymphs to resultant adults. The temperatures above 40 degrees C and below 12 degrees C prevented moulting. Maximum infection levels were obtained in salivary glands of adult ticks when the infected engorged nymphs were incubated at 24-28 degrees C. The infection rate in salivary glands was assessed using a methyl green pyronin technique. PMID- 1763486 TI - Treatment of stephanofilariosis ('earsore') with ivermectin. AB - Thirty-four adult male buffaloes with clinical signs of 'earsore' were used to determine the efficacy of ivermectin against Stephanofilaria zaheeri. On the basis of parasite counts in skin scrapings, ivermectin was effective as a microfilaricide. Adult parasite counts were reduced, but removal of adults was incomplete. Clinical improvement was recorded in more than half of the treated buffaloes, but constant reinfection meant that meaningful interpretations were not possible. PMID- 1763487 TI - Spiculopteragia spiculoptera, S. asymmetrica and Ostertagia leptospicularis from Cervus elaphus in La Pampa, Argentina. AB - The nematode species Spiculopteragia spiculoptera, Spiculopteragia asymmetrica and Ostertagia leptospicularis were recovered from the abomasum of wild red deer, Cervus elaphus, in the forest area of the semi-arid Pampeana Region of La Pampa (Argentina) for the first time. Oesophagostomum venulosum and Dictyocaulus spp. were also found. PMID- 1763488 TI - Coccidia of the llama, Lama glama, in Colorado and Wyoming. AB - Fecal samples were collected from 144 llamas, Lama glama, on four premises in northern Colorado and southern Wyoming. Feces were examined for the presence of coccidial oocysts; Eimeria alpacae was found in 55.6%, Eimeria lamae in 67.3% and Eimeria macusaniensis in 1.4% of the samples. An adult female llama was found to be infected with Eimeria macusaniensis at necropsy. This is the first report of these species of coccidia in the llama. PMID- 1763489 TI - Gastro-intestinal parasitism of cattle in native pasture grazing system in Guadeloupe (French West Indies). AB - Gastro-intestinal parasitism of creole cows and calves, Limousin x creole cross calves and Brahman x creole cross calves was recorded during seasons of calving in a native grazing system in Guadeloupe, a wet tropical area. Calvings were pooled during the dry season for two herds and during the rainy season for two other herds. For each calving season, calves of one herd were drenched monthly with anthelmintic. A marked periparturient rise in egg excretion was observed in cows. Coccidial infection was always present in calves, but no clinical signs were observed. The main parasites during the first 2 months of life were Strongyloides papillosus and Toxocara vitulorum. Then, Haemonchus placei, Trichostrongylus spp. and Cooperia spp. were the dominant species encountered. Brahman cross calves were the most heavily infested animals. There was no clear relationship between third stage larvae (L3) population size on pasture and worm burdens in calves, except during the second month of life. Despite medium levels of infestation, parasitism inhibited the growth of creole calves: -10.5 kg of bodyweight at weaning (-59 g day-1 of daily bodyweight gain from birth to weaning). The pathological effects of subclinical parasitism were confirmed by a lower packed cell volume and albuminaemia in parasitized calves than in treated calves. PMID- 1763490 TI - Survival of snails and characteristic lesions of Fasciola hepatica infection in four European species of Lymnaea. AB - The survival of snails and characteristic organ lesions were investigated in four different age categories (new-born, 1 and 2 mm shell height, adults) and in four species of Lymnaea (L. glabra, L. palustris, L. peregra ovata, L. truncatula) infected by Fasciola hepatica. Mortalities were higher in infected groups on Days 30 and 45 post-infection (+42% and +45%, respectively) than in controls. Lesions depended on the species and age of the Lymnaea. Epithelial necrosis of the kidney was recorded in L. glabra, L. palustris and L. p. ovata, whereas intralamellar deposits were found in the same organ of L. truncatula. All categories of L. truncatula had evolutive infections (snails with living parthenitae); the young snails of other species became infected, but the adults did not, as estimated at Day 45 post-infection. The lesions were related to the intensity of evolutive infections: necrosis of the digestive gland was found in moderate to low infections and, conversely, gonadal atrophy with epithelial necrosis was found in highly infected snails. PMID- 1763491 TI - Efficacy of albendazole, levamisole and fenbendazole against gastrointestinal nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae. AB - An experiment was conducted to compare the anthelmintic efficacy of albendazole (ABZ), levamisole (LEV) and fenbendazole (FBZ) against inhibited early fourth stage larvae (EL4) of Ostertagia ostertagi during April in Louisiana. Forty cross bred beef heifers (average weight 165 kg) were acquired during winter and grazed on pastures contaminated with O. ostertagi and other nematodes until early April. The cattle were weighed and randomly allotted into four groups of ten animals on 6 April and treatments were administered on 7 April. Experimental groupings were: Group 1, non-treated controls; Group 2, ABZ by oral drench at 10 mg kg-1; Group 3, LEV by topical, pour-on administration to back midline at 10 mg kg-1; Group 4, FBZ by oral drench at 10 mg kg-1. Equal numbers of cattle from each group were slaughtered daily between 10 and 13 days after treatment. Mean numbers of O. ostertagi developmental stages present in untreated controls were: adults, 13,714; developing L4 (DL4), 6487; inhibited EL4, 21,719. The mean percentage of inhibited EL4 was 51.8. Smaller numbers of Haemonchus placei, Trichostrongylus axei and Cooperia spp. were recovered uniformly in control cattle. Percentage reduction values for the three compounds against O. ostertagi adults, DL4 and EL4, respectively, were: ABZ, 99.0, 95.3, 84.9; LEV, 1.0, 21.8, 32.1; FBZ, 99.2, 97.2, 97.5. Differences between ABZ and LEV EL4 counts were not significant, but in all other cases worm counts in ABZ and FBZ-treated cattle were significantly lower (P less than or equal to 0.05) than in LEV-treated and control cattle. Both ABZ and FBZ were 98-100% effective against Haemonchus adults and L4, T. axei adults, and Cooperia spp. adults and L4. LEV was 100% effective against Haemonchus adults and L4, 85.6% against T. axei, and 94.6% and 89.59% effective against Cooperia spp. adults and L4, respectively. PMID- 1763492 TI - Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January). AB - Levamisole (LEV) was tested in four experiments to compare efficacy values against Ostertagia ostertagi when larval maturation was occurring (September), following inhibition and also when populations were expected to be largely adult (winter). A primary objective was to determine the importance of developing fourth-stage larvae (DL4) and inhibited, early fourth-stage larvae (EL4) in replacing adult worms lost through treatment and the effect of this on reduced efficacy against adult worms. Young crossbred beef calves ranging in weight from 150 to 230 kg were used in the first (September 1981), second (September 1983) and third experiments (January 1987). Jersey calves of 110 kg average weight were used in the fourth experiment (December 1988). Calves were randomized to groups according to weight and group sizes ranged from three to five calves. All parasite infections were naturally acquired, but a mixture of nematode third stage larvae (L3) (22,500 per calf), including 20% Ostertagia ostertagi, was inoculated into Jersey calves of Experiment 4 following a 2 week exposure to natural infection. All LEV treatments were by subcutaneous injection at dosages of 6 and 8 mg kg-1. Treatment with ivermectin was used only in Experiment 3 as an efficacy reference. All calves were killed at 8-10 days after treatment. The efficacy of LEV against all developmental stages of Ostertagia ostertagi was consistently low in all experiments and a dose-dependent response was not evident. Large numbers of all Ostertagia ostertagi developmental stages were present in non-treated calves in both September experiments. Percent reduction of adults, DL4 and EL4 at the 6 mg kg-1 and 8 mg kg-1 dosages, respectively, were adults, 51.7 and 23.6 (1981), 8.7 and 51.3 (1983); DL4 40.3 and 13.2 (1981), 37.9 and 33.1 (1983); EL4, 19.6 and 0 (1981), 59.6 and 42.9 (1983). Smaller numbers of Ostertagia ostertagi were present in winter experiments and adult worms greatly outnumbered larval stages. Percent reductions of adults, DL4 and EL4, respectively, were (1987) LEV 6 mg kg-1, 40.2, 0 and 0; ivermectin 200 micrograms kg-1, 98.7, 97.7 and 100.0; (1988) LEV 6 mg kg-1, 62.4, 100.0 and 100.0; LEV 8 mg kg-1, 49.1 65.0 and 74.1. Too few larval stages were present in the latter experiment for valid efficacy values.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1763493 TI - Effects of time of day, season and stratum on Haemonchus contortus and Haemonchus placei third-stage larvae on irrigated pasture. AB - The effect of time of day, season and stratum of herbage and soil on the availability of Haemonchus contortus and Haemonchus placei third-stage larvae (L3) on pasture was assessed. Feces from infected calves and lambs were placed on pasture plots and samples of upper herbage, lower herbage, mat and soil were collected at five intervals per day throughout the daylight hours on 18 sample days over 12 months. Using recovery rate factors derived from a preliminary investigation on the efficacy of larval recovery from each stratum, the data on larval recoveries were analyzed for the effect of season, time and stratum, and their interactions. Significant (P less than 0.05) differences were found for season, stratum and the season-with-stratum interaction for both parasites. No significant differences were detected for larval counts at different times of the day. Larval recoveries of H. contortus were larger throughout the study than those of H. placei. Most H. contortus L3 were recovered in the summer and autumn, and H. placei in the spring and summer. For both parasites, the recoveries of larvae from the upper and lower herbage were larger than those from the mat and soil. The implications of these findings are discussed in terms of control strategies. PMID- 1763494 TI - Interaction of parasitism and nutrition and their effects on production and clinical parameters in goats. AB - Weaned wether goats (n = 144) approximately 6 months of age were placed in a 2 x 3 factorial design experiment for 5 months to test the main effects and interaction of two levels of nutrition (growth + maintenance, NUT1; twice growth + maintenance, NUT2) and three levels of Haemonchus contortus burden (0, 500 and 2000 larvae administered every 2 weeks: W0, W500 W2000, respectively) on weight, feed intake, level of infection and packed cell volume (PCV). The rationale for the experimental design was based on the lack of information concerning the interaction between nutritional status and worm burden. Results indicated significant effects of worm burden levels on PCV, faecal egg contents (eggs per gram of feces (EPG)), actual worm numbers, feed intake and efficiency of feed utilization. Nutrition x worm burden interactions were also significant for PCV and EPG. However, the differences detected for PCV and actual worm numbers did not translate into large or consistent differences in body weight. Goats on NUT2, after an initial period, showed little difference in body weight, irrespective of worm burden. Within the NUT1 level, W0 kids weighed more than W500 or W2000 kids throughout the study. Although not statistically significant, this constitutes a trend towards an interaction between nutrition and worm burden. In both nutrition levels, there were no body weight differences between W500 and W2000 until the last 14 days. Feed intake was depressed in the first 3 months of the experiment for infected animals, but was subsequently followed by a compensatory reaction. Lower establishment rates, based on actual worm counts, were observed for the higher infection level, but in both infection levels establishment rates tended to decrease with time. Nutrition was found to be more important to counteract the consequences of a parasitic infection than to counteract the establishment of that same infection. PMID- 1763495 TI - Quantitation of soluble HLA class II molecules by an enzyme-linked immunosorbent assay. AB - In order to quantify soluble HLA-DR,DQ,DP molecules (sHLA-RQP) an enzyme-linked immunosorbent assay was developed utilizing two monoclonal antibodies specific for HLA-DR,DP (Tu35) and HLA-DQ (Tu22) gene products, respectively. Highly purified HLA class II molecules isolated from a lymphoblastoid cell line were used for calculation of exact sHLA-RQP protein values. Circadian variations of sHLA-RQP plasma levels were studied in 7 healthy probands showing no significant deviations; measurements in 4 probands at intervals between 4 and 6 weeks revealed that sHLA-RQP levels remain relatively stable. The population analysis of 209 unrelated, HLA-typed healthy donors resulted in an average protein concentration of 1.53 +/- 2.44 micrograms/ml plasma for sHLA-RQP. Four out of 209 probands (= 1.9%) had no detectable sHLA-RQP. Significant associations of high or low sHLA-RQP levels to particular HLA-DR or -DQ specificities were not observed. However, plasma derived from HLA-DR9 positive had the highest and from HLA-DR8 positive donors the lowest mean sHLA-RQP values. By comparing HLA identical with two-haplotype-different siblings we found no evidence that sHLA-RQP plasma levels are under genetic control of the HLA complex or closely linked genes. Furthermore, soluble HLA class I plasma concentrations in 100 probands analyzed showed no correlation to those of sHLA-RQP. PMID- 1763496 TI - Platelet antibody binding and spontaneous aggregation in 21 lupus anticoagulant patients. AB - In order to ascertain the role of the antiphospholipid antibody in the pathogenesis of thrombotic disorders, a study of 21 lupus anticoagulant-positive patients was done by a number of serologic and functional platelet tests. In immunofluorescent studies, we found that 80% showed a mitochondrial pattern on HEp cells and all patients gave an ubiquitously intense staining of donor platelets. By a microscopic spontaneous aggregation test, all lupus anticoagulant positive patients showed accelerated platelet aggregation which was calcium independent. The results show that the plasma of lupus anticoagulant-positive patients contains a platelet-binding antibody and causes spontaneous agglutination of platelets. These properties may play a role in the thrombogenesis common to the antiphospholipid syndrome. PMID- 1763497 TI - Serology and genetics of the red blood cell factor Rh34. AB - Rh34 antibodies were found to have a unique, previously only partly characterised, specificity within the Rh system. No evidence was seen that they were mixtures of hrB and Hr-like antibodies, or that hrB antibodies existed independently in the natural state. The term anti-hrB applied to Rh34 antibodies after they had been partially absorbed with R2R2 red cells. Four haplotypes not expressing Rh34 antigen were identified in the present study. The prefix * has been used to indicate them in this text. They were *r's (*dCces), *Ro (*Dce), *Rou (*D(uce)) and *R(od) (category III *Dce). Red cells with partially deleted or Rh(null) phenotypes were therefore not the sole red cells compatible with anti Rh34. R2R2 red cells, which are known to carry weak Rh34 antigen, were incompatible. Twenty-two family and mother-child studies established that the Rh: 34 haplotypes were inherited as normal Mendelian dominant characters. Anti-Rh34 was capable of recognising RH 34 dosage and of excluding some men who had been wrongly accused in disputed paternity tests. PMID- 1763498 TI - Autologous blood transfusion. PMID- 1763499 TI - Isolated anti-HBc and hepatitis B virus occult infection. PMID- 1763500 TI - Concomitant exposure of Tn and Th cryptantigens on the red cells of a patient with myelodysplasia. PMID- 1763501 TI - Can anti-HBc testing decrease the residual risk of transfusion-related HIV transmission? PMID- 1763502 TI - Autologous transfusion--too far, too soon? PMID- 1763503 TI - Effect of EDTA on platelet count and other platelet parameters in blood and blood components collected with CPDA-1. AB - We have shown in this study that addition of dried K2EDTA (1.5 mg/ml) to blood samples anticoagulated with CPDA-1 increases significantly the platelet count and mean platelet volume (MPV) of whole blood, red cell concentrate (RCC) and platelet concentrate (PC), but not of platelet-rich plasma (PRP) or of platelet poor plasma (PPP). Transmission and scanning electron microscopy illustrated that platelet aggregates which are present in some components are dispersed on mixing of the sample with EDTA and that this is accompanied by a change in platelet morphology. Determination of the platelet distribution width (PDW) indicated that the platelet populations in whole blood and RCC seem to be more uniform in size than the populations in PRP, PPP and PC. The determination of MPV and PDW changes after addition of EDTA may provide a new approach to quality control of PC. PMID- 1763504 TI - The influence of cryopreservation on activity and surface markers of lymphokine activated killer cells. AB - Ficoll-separated and monocyte-depleted mononuclear cells isolated from normal leukapheresis products were cryopreserved. These cells were incubated with or without 1,000 U/ml of recombinant interleukin-2 (rIL-2) for 4 days, and their lymphokine-activated killer (LAK) and natural killer (NK) activities were measured. IL-2 activation induced a significant increase in the expression of the CD25 antigen. There was no change in CD2, CD3, CD4, CD8, CD16, CD56 and CD57 cell marker expression. Cryopreservation did not induce any change in the membrane antigen expression and in the lymphocyte subsets. The NK activity was well preserved and the decrease of LAK activity of IL-2-activated cells after cryopreservation was not significant. In contrast, cells activated before cryopreservation had a significantly lower cytotoxic activity and the number of cells expressing the IL-2 receptor was also significantly reduced. However, the decrease of CD56 expression was not significant. CD25 expression seemed to be proportional to the LAK activity of the cells. This study demonstrated that cryopreserved lymphocytes, after 4 days of culture with rIL-2, could be as active and could express the CD25 and CD56 cell surface markers in the same manner as fresh LAK cells. PMID- 1763505 TI - Intravenous drug abuse causes Rh immunization. AB - Intravenous drug abuse causes many health problems. From March 1989 to January 1990 of 27 Rh-negative women (28 pregnancies) referred to our centre, 4 women (5 pregnancies) were Rh immunized due to the sharing of needles and blood with their Rh-positive partners. Severe hydrops was present in 4 of their 5 fetuses when they were first seen at 17-35 weeks of gestation. Only the fetus first seen at 35 weeks survived. That infant was moribund at birth and now has evidence of leukomalacia and porencephaly. The fifth fetus, not hydropic, required two intravascular fetal transfusions in order to survive. A fifth woman, immunized in a similar manner, had a spontaneous abortion. These fetuses represent some of the earliest and severest examples of hydrops fetalis ever seen at our centre. The severity of their fetal hemolytic disease is probably due to the fact that their mothers' exposure to Rh(D) antigen by blood sharing was continuous and ongoing. Because of their aberrant behaviour, these women have suffered irreversible reproductive damage. PMID- 1763506 TI - [Effect of structured ambulatory training of patients with chronic respiratory tract diseases on the efficiency of long-term care]. AB - In spite of the availability and widespread use of a number of effective medications, the frequency of severe attacks of asthma bronchiale including those with fatal outcome has not decreased. One possible reason for this is the delay in therapeutic intervention of up to 30 minutes resulting either from transport time to a hospital or from the response time of mobile ambulance services. Treatment delays are also frequent co-factors for decreased well-being in non emergency cases. Prompt initiation of countermeasures, regardless of time or place, can only be guaranteed when the patient himself is capable of carrying them out with the same expertise as his attending physician. Toward this end, a model patient-training program was investigated. The didactic goal of the training was to make the patient an expert in his chronic disease. The medical goal of the training was to improve the quality of a complex long-term therapy and with it, the patient's well-being and quality of life. The content of the training corresponded largely to that contained in a lecture series for medical students or physicians on the same subject. Style and choice of words (avoidance or explanation of medical terminology) was of course adapted to the lay-status of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1763507 TI - [Clinical epidemiologic data of malignant melanoma based on 1,368 patients of the Graz University Dermatology Clinic (1970-1989)]. AB - Epidemiological and histological data of 1368 patients with invasive malignant melanoma treated at the Department of Dermatology between 1970 and 1989 were analysed retrospectively. Frequency of melanoma increased from 103 cases between 1970 and 1974 to 593 between 1985 and 1989. The male/female ratio was 1/1.5 and did not change during the study period. Mean age of patients at the time of primary operation was 56.1 years and was approximately the same for males and females (males 55.8, females 56.3 years). The predominant site was the trunk in males (58.7 per cent) and the lower leg in females (41.6 per cent). There was a relative increase of melanomas of the back in males and the lower leg in females at the expense of melanomas of the face. The Breslow index was significantly higher in males than in females. In patients older than 69 years, the proportion of thick melanomas was above average. During the study period, the frequency of thick melanomas (greater than 1.5 mm) showed an encouraging decrease in both sexes. In 1989, 50 per cent of all melanomas were thinner than 1.01 mm. This can be interpreted as a successful outcome of efforts in preventive medicine. PMID- 1763508 TI - [Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts]. AB - In Austria it is illegal to sell tobacco to young adolescents. A diverse sample of 358 narcotic addicts was investigated at the Psychiatric University Clinic of Vienna. Data were obtained from on site confidential interviews and a HIV-test was conducted. The individual drug use history was recorded and, interestingly, tobacco addiction was the first stage in starting a drug career. Furthermore, a strong correlation was observed between onset of heroin use and HIV-1 infection. It is concluded that in Austria not only the availability nicotine and alcohol to young adolescents should be prohibited, but also their use should be punishable. Easy access to nicotine as in public restaurants or from automatic distributors, has to be withdrawn. Tobacco advertisements may drive vulnerable young adolescents to early nicotine abuse and this may be followed by addition to other drugs and diseases causing death, including AIDS. Socioeconomic data, as well as the methadone data are presented. 180 out of the 358 patients were on methadone maintenance. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Physicians have a clear responsibility to lead the effort on all fronts against tobacco, especially in view of the HIV epidemic. PMID- 1763509 TI - Familial defective apolipoprotein B-100: molecular basis, prevalence and clinical features. AB - Familial defective apo B-100 is an autosomal dominant trait which causes moderate to severe elevation of LDL-cholesterol in the plasma and may predispose the coronary heart disease. The primary defect is a single amino acid change (Arg3500 to Gln), which disrupts the normal binding of LDL to the LDL-receptor. The mutation occurs at an estimated frequency of 1/600 in the normal population and is, therefore one of the most common known single-gene defects causing an inherited abnormality. PMID- 1763510 TI - [Recurrent epicondylitis after Wilhelm's operation and its treatment]. AB - Three patients among 107 operated on before 1985 according to Wilhelm's procedure for epicondylitis humero radialis showed no therapeutic response due to insufficient discission of the extensor carpi radialis brevis. We successfully used Garden's procedure at reoperation, with lengthening of the extensor carpi radialis brevis at the distal part of the forearm. As a direct result of our experience with these cases of recurrent epicondylitis we now consider a combination of the Garden and Wilhelm procedures the method of choice in treating patients suffering from the primary ligamentum anulare syndrome with shortened musculus extensor carpi radialis brevis. Two patients primarily treated according to the combined procedure have shown a successful result on follow-up over 60 and 55 months, respectively. PMID- 1763511 TI - Therapeutic approaches to Lambert-Eaton myasthenic syndrome in the intra individual comparison. AB - A patient with Lambert-Eaton myasthenic syndrome was clinically treated several times over a period of 9 months. During at least 3 weeks each time, the patient received prednisone, then underwent 9 plasmaphereses, and was given guanidine hydrochloride (HCl) and 3,4-diaminopyridine (3,4-DAP). The muscle-power scoring, muscle function tests and the electrophysiological parameters showed a superiority of 3,4-DAP over the other pharmacological therapies. Good results were also obtained with plasmapheresis. Corticoid medication proved to be less effective. No improvement was seen with guanidine-HCl. For comparative judgement, two months after beginning the last therapy, the patient and the attending physician were questioned with regard to subjective therapeutic success. The answers largely match the objective results. Both favour 3,4-DAP. In contrast to the patient's opinion, the physician sees a distinct effect of plasmapheresis. All in all, the administration of 3,4-DAP may be seen as an effective and acceptable therapy in Lambert-Eaton myasthenic syndrome. PMID- 1763512 TI - [15-year-factor analysis of multiple sclerosis]. AB - The authors have conducted a longitudinal survey for a period of 14 years with 171 patients suffering from multiple sclerosis. In each case, therapeutic and diagnostic procedures were in accordance with the latest development. In almost half of the cases with a duration of illness up to 20 years the degree of impairment can be regarded as minimal, which can be used as an argument in favour of conscientious and continuous rehabilitative measures, including psychotherapy (this in opposition to a "rehabilitative pessimism"). Two thirds of the patients have been in employment with full working capacity during the first ten years of their illness. The consequences for social medicine and social policy are self evident and imperative. In accordance with earlier studies, motor pareses are predominant among the first symptoms of multiple sclerosis, whereas disorders of cranial nerves, of urinary excretion and of cerebral function appear later in the course of the disease. Factor analysis did not yield any clues with respect to the predictability of the development of illness. Psychoreactive depression is relatively common in the earlier stages, later we can find somatogenic (psycho organic) depressions, which respond relatively poor to treatment. Among the diagnostic tool, analysis of the critical flicker fusion frequency (CFFF) has proved to be very sensitive, by far not as cumbersome as visually evoked potentials and at least as reliable as the later. Therapeutic strategies should include: early treatment of any acute attack, consequent long-term care with modern nursing methods and rational concomitant medication, prophylaxis against infection. Multiple sclerosis represents itself as a problem of long-term rehabilitation, thus emphasizing the necessity of increased commitment to rehabilitation within a general framework of health care, which should include: a) better representation of rehabilitation as a discipline at the universities. b) systematic concomitant research in rehabilitation, c) legal and administrative adaptations, d) the development of a general "rehabilitation mentality" (as we have come to call it), which means involvement with the patient and his environment throughout his entire life-span. PMID- 1763513 TI - [Alzheimer dementia. A clinical long-term study with quantitative neuropathology]. AB - Alzheimer's disease causes about 80% of dementias in old age. The pathological hallmarks of Alzheimer's disease are senile plaques (SP) and neurofibrillary tangles (NFT), which to a lesser degree can also be found in the brains of mentally intact elderly. The question whether SP or NFT or any other process are primarily correlated to severity of dementia can only be answered in prospective longitudinal clinical and neuropsychological studies with quantitative neuropathological investigation. We report the correlations between mini-mental state scores and lesion counts in 3 isocortical and 3 hippocampal areas in a consecutive series of 19 Alzheimer's patients studied prospectively in the Vienna Longitudinal Study on Dementia. Lesion counts increased at very late stages of dementia and were rather low in mild to moderate severity of dementia. Mildly demented patients with very slow progression of dementia also had rather high lesion counts. Neurofibrillary changes in NFT and neuritic plaques were correlated with severity of dementia, but diffuse plaques, i.e. SP without neuritic degeneration, were not at all correlated with severity of dementia. We speculate that NFT and SP do not represent the primary process which leads to dementia. PMID- 1763514 TI - [The confused and the demented patient as a problem in neuro-rehabilitation. Old age rehabilitation]. AB - Organic psychosyndromes may be classified 1) by the state of vigilance (agitated or reduced), 2) by the progress in time (episodic versus progressive), 3) by the presence or absence of brain-local or vegetative accompanying phenomena, 4) by etiology. The most frequent forms are: multi-infarct-dementia and primary degenerative dementia of Alzheimer's type. We must be aware that this didactic differential diagnosis in reality mostly shows overlapping criteria. Either more to the one side or more to the other. Etiological therapy (as well "vasoactive" as "nootropic") should in most cases be combined with therapy of underlying internistic (cardiac for example) and accompanying (infection for example) symptoms. Depression as a special frequent dimension needs special attention. Furthermore there are complex therapeutic possibilities in the social, recreative, psychologic, rehabilitative, psychotherapeutic etc. field. Relatives need to be treated concommitantly. Only thus scientific as well as human implications for rehabilitation can meet. PMID- 1763515 TI - [The horse as an aid in therapy]. AB - Physiotherapy on the back of the moved horse has two important dimensions: 1) The somatotropic effect regards mainly spasticity, ataxia, the vertebral column, the basis of the pelvis and the skin. 2) A general psychotherapeutic and psychohygienic effect is created by joy, change and new impetus in rehabilitation and by the emotional contact with the "comrade animal". Or unit was the first to introduce hippotherapy with adults in Austria. There is specially good experience with the spastic atactic component in multiple sclerosis. However other diagnosis as well showed good profit, such as stroke, etc. Some good effects in cephalaea patients indicate transition to riding as a medical pedagogic instrument with further transitions to psychosomatic patients. We want to proceed in this direction. Well organized hippotherapy is cheaper than the hydrotherapy (being current almost everywhere. Therefore opposition against the valuable hippotherapy by reasons of economics should be ruled out. Today's medicine goes farther and farther away from natural possibilities (slogan: "overtechnologized"). We see in hippotherapy an important counterweight in the sense of a valuable methodology towards holistic therapy especially in rehabilitation. PMID- 1763516 TI - Verofylline pharmacokinetics in dietary-induced obese rats: role of fat mass and protein binding in determining volume of distribution. AB - 1. Verofylline, a lipophilic polysubstituted methylxanthine, was utilized to examine how severely altered body composition in obesity affects drug disposition; the role of fat-free mass, fat mass and protein binding in determining the volume of distribution (Vss) was investigated. Obesity was induced by feeding Sprague-Dawley rats for 8 months with a calorie-dense diet; the obese rats showed increases of 50% in total body mass and 150% in body fat. 2. Both the absolute Vss and the clearance (Cl) in the obese rats increased 2 fold over control. Since Cl and Vss increased similarly, the half-life of verofylline in obese rats did not change. 3. The increase of Cl in obese rats can be accounted for by metabolic function related to fat-free mass and decreased serum binding. Similarly, an increase in fraction unbound and in total body mass accounted for the increase in Vss. 4. Based on in vitro measurements of muscle and fat tissue uptake of verofylline, and the assumed body space (from tritium dilution method), the predicted values for Vss closely approximated those of observed values. The semi-physiological model proposed here appears adequate to relate changes of body composition and serum protein binding in obesity to Vss. PMID- 1763517 TI - Investigations on the biotransformation of mebendazole using an isolated perfused rat gut system. AB - 1. The intestinal metabolism of the benzimidazole, mebendazole (MEB), has been investigated using isolated perfused jejunal segments of rats. Significant absorption and intestinal metabolism of the substance was observed. 2. The metabolites, the reduced alpha-hydroxy-analogue, its glucuronide, and the decarbamoylated 2-amino-analogue, were transported into the resorbate collected at the serosal side or were resecreted into the gut lumen. 3. The intestinal decarbamoylation of mebendazole increased up to 20-fold after pretreatment with 3 methylcholanthrene (MC), and complete re-secretion of this metabolite into the gut lumen led to a total loss of the absorption of mebendazole and metabolites across the gut wall. 4. The results indicate the ability of the gut to metabolize mebendazole by phase I and II reactions. 5. An almost complete loss of bioavailability after induction of the gut enzyme system by MC was observed. PMID- 1763518 TI - Quinine is a more potent inhibitor than quinidine in rat of the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase. AB - 1. Lewis rats (n = 7 or 8) were dosed with methoxyphenamine with and without prior administration of various doses of either quinine or its diastereomer quinidine. Methoxyphenamine and its N-desmethyl, O-desmethyl and aromatic 5 hydroxy metabolites were quantified in 0-24 h urine. 2. The oxidative routes of methoxyphenamine metabolism which had been previously shown to involve the debrisoquine/sparteine isoenzyme, namely O-demethylation and 5-hydroxylation, were both significantly inhibited by quinine. The inhibition was selective in that N-demethylation which does not involve this isoenzyme was not affected by quinine. 3. Quinidine which had been previously shown at a relatively high dose (80 mg/kg) to affect the three metabolic routes of methoxyphenamine in a similar fashion was ineffective in this regard at a 25 mg/kg dose. Quinine more effectively inhibited the O-demethylation and 5-hydroxylation of methoxyphenamine than did quinidine, and its inhibition was marked at the lowest dose examined, 12.5 mg/kg. 4. As quinidine is a more potent inhibitor than quinine of debrisoquine 4-hydroxylase in man, the rat should be used only with full realization of its limitations when investigating substrates metabolized by this isoenzyme. PMID- 1763519 TI - The metabolites of chlorpromazine N-oxide in rat bile. AB - 1. The metabolism of chlorpromazine N-oxide was studied in female rats after a 20 mg/kg single i.p. dose. 2. Metabolites identified in urine and faeces were chlorpromazine, 7-hydroxychlorpromazine, chlorpromazine sulphoxide, N desmethylchlorpromazine and N-desmethylchlorpromazine sulphoxide. As these same five metabolites were previously shown to be present after oral administration this indicates that reduction of chlorpromazine N-oxide occurs not only in the gastrointestinal tract but also at other sites. 3. The metabolism of chlorpromazine N-oxide was studied following its administration by either i.p., i.v. or oral routes to female rats in which the bile duct was cannulated. 4. There were no qualitative differences between the three routes of administration with respect to the metabolites identified. With the exception of the absence of N-desmethylchlorpromazine and N-desmethylchlorpromazine sulphoxide, all metabolites previously identified in urine and faeces were also present in bile. 5. Additionally there were three compounds present in rat bile which were not identified in urine or faeces. These were chlorpromazine N-oxide, chlorpromazine N,S-dioxide and 7-hydroxychlorpromazine O-glucuronide. This is the first unequivocal evidence for the identification of intact 7-hydroxychlorpromazine O glucuronide in any species. 6. The inability to detect chlorpromazine N-oxide and chlorpromazine N,S-dioxide in the faeces of rats is likely to be due to the reduction of the N-oxide group on the passage of these biliary metabolites down the intestinal tract. PMID- 1763520 TI - Inhibition and induction of drug metabolism by psoralens: alterations in duration of sleep induced by hexobarbital and in clearance of caffeine and hexobarbital in mice. AB - 1. Hexobarbital (100 mg/kg i.p.) sleeping times in male CD-1 mice pretreated (-1 h) with a single i.p. injection of 150 mumol/kg of psoralen or coumarin analogues were increased, most markedly (6-fold) by linear, methoxy-substituted psoralens. 2. Hexobarbital sleeping times of mice which received three daily injections (231 mumol/kg; 50 mg/kg) of 8-methoxypsoralen (8-MOP) were 44% of controls (corn oil). 3. The whole-body half-life of caffeine (1 mg) in mice was 10.2, 1.2, and 0.37 h following 8-MOP (50 mg/kg per day) x 1, vehicle, and 8-MOP x 3 respectively. 4. The whole-body concentrations of hexobarbital (100 mg/kg dose) in mice 30 min after dosing were 14.3 +/- 0.9, 8.4 +/- 0.3, and 5.2 +/- 0.5 micrograms/ml (1 mouse = 150 ml) following 8-MOP (50 mg/kg per day) x 1, vehicle, and 8-MOP x 3 respectively. 5. It is concluded that, administered acutely, psoralen analogues inhibit hexobarbital metabolism in mice; and 8-MOP administered acutely inhibits the metabolism of caffeine and hexobarbital, but administered repeatedly increases their metabolism. PMID- 1763521 TI - The metabolism and excretion of prochloraz, an imidazole-based fungicide, in the rat. AB - 1. Following oral administration of prochloraz (1-[N-propyl-N-2-(2,4,6 trichlorophenoxy)ethylcarbamoyl]imidazole) at 100 mg/kg body weight to rats, the compound underwent extensive metabolism, the primary route appearing to be opening of the imidazole ring followed by hydrolysis of the alkyl chain. The major metabolites were 2,4,6-trichlorophenoxyacetic acid and 2-(2,4,6 trichlorophenoxy)ethanol, which is present mainly as a glucuronide conjugate. Ring hydroxylation occurred to produce several minor metabolites. No unchanged prochloraz was excreted in the urine. 2. Tissue residues 96 h after dosing were generally less than 1 mg prochloraz equivalents/kg tissue. The highest residues were found in the liver (2.8-5.1 mg prochloraz equivalents/kg tissue) and kidney (1.5-2.1 mg prochloraz equivalents/kg tissue), the principal organs of metabolism and excretion. Residues in female rats were generally slightly higher than those found in males. 3. The metabolites were quantitatively excreted within 96 h, with greater than 50% of the dosed radioactivity being found in the 0-24 h excreta. Urinary excretion accounted for 65% dose in male and 41% in female rats, respectively. PMID- 1763522 TI - Species- and sex-related differences in the plasma clearance and metabolite formation of antipyrine. A comparative study in four animal species: cattle, goat, rat and rabbit. AB - 1. The plasma disposition of antipyrine, and its urinary metabolite pattern, were studied in both sexes of four animal species: rat, dwarf goat, rabbit and cattle. 2. No sex differences in plasma elimination of antipyrine were found in rabbit and goat; however, in rat and cattle the effect of sex was marked. As expected, male rat showed a higher plasma clearance value than female. In contrast bulls showed a significantly lower clearance value than cows. 3. Metabolite patterns varied widely from one species to another. The major urinary metabolite in rabbit and the two ruminant species was 4-hydroxy-antipyrine (OHA), whereas in rat 3 hydroxymethylantipyrine (HMA) was quantitatively the most important metabolite. 4. HMA was excreted in the 24 h urine in larger amounts by male rats than by females. Metabolism of antipyrine to HMA was also sexually different in the dwarf goat, but in this species females were more active than males. The effect of sex on the metabolite pattern in cattle was marked. 5. It is concluded that in ruminants there may be xenobiotic metabolic pathways which are under hormonal control, just as there are in rats and mice. If hormones influence drug metabolism in food-producing animals, residue levels of xenobiotics or their metabolites in food from animal origin may differ with the sex of the animal, or may be altered after treatment with anabolic hormones. PMID- 1763523 TI - Identification of novel phencyclidine metabolites formed in vitro by rabbit microsomal metabolism. AB - 1. Phencyclidine (PCP) was incubated with rabbit liver and brain microsomal fractions, and the structures of metabolites formed by oxidation determined by g.l.c.-mass spectrometry. 2. The formation of several known mono- and di hydroxylated metabolites, as well as two new metabolites, was seen in the liver preparations. 3. Hydroxylated PCP metabolites were also formed after incubation of PCP with brain microsomes, indicating that PCP biotransformation may occur in the brain itself. PMID- 1763524 TI - Thebaine O-demethylation to oripavine: genetic differences between two rat strains. AB - 1. Codeine O-demethylation to morphine is mediated by cytochrome P450 IID1 (rat), or P450 IID6 (man), and exhibits genetic polymorphism. Thebaine is a precursor in the formation of endogenous morphine and codeine in man, being O-demethylated to oripavine. 2. The objective of the present study was to ascertain whether the O demethylation of thebaine to oripavine was mediated by cytochrome P450 IID1 in rat liver microsomes. 3. Thebaine O-demethylation showed strain differences in female Sprague-Dawley (SD) and female Dark-Agouti (DA) rats, which serve as a model for the human debrisoquine/sparteine metabolism phenotypes. 4. The total intrinsic clearance of thebaine to oripavine was high (19.7 ml/h per mg protein) in SD rats, indicating that oripavine is a major metabolite of thebaine. A 3-fold lower intrinsic clearance was observed in DA rats (6.7 ml/h per mg protein). 5. Thebaine O-demethylation was inhibited by quinine and known substrates of cytochrome P450 IID1/P450 IID6, supporting the major involvement of cytochrome P450 IID1 in oripavine formation in rats. PMID- 1763525 TI - Comparative pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline in rainbow trout (Oncorhynchus mykiss). AB - 1. The pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline were studied in rainbow trout at a water temperature of 16 degrees C after intravascular (10 and 20 mg/kg, respectively) and oral (75 mg/kg) dosing. 2. The pharmacokinetics were best described by a two-compartment open model giving distribution half-lives of 0.31 h and 1.53 h, and elimination half-lives of 69.7 h and 60.3 h for oxolinic acid and oxytetracycline, respectively. The respective volumes of distribution (Vdarea) were 1.94 l/kg and 1.34 l/kg. 3. The apparent oral bioavailability for oxolinic acid and oxytetracycline was 13.6% and 5.6%. 4. The plasma protein binding was 27% for oxolinic acid and 55% for oxytetracycline. 5. Both drugs were well tolerated, the acute oral toxicities (LD50) exceeding 4000 mg/kg. PMID- 1763526 TI - Identification of a hydroxy metabolite of diflunisal in rat and human urine. AB - 1. A new metabolite of diflunisal, a hydroxy derivative, has been identified in rat and human urine following administration of diflunisal. 2. This hydroxy metabolite of diflunisal is excreted in urine of both species as a polar conjugate, most likely a sulphate. 3. Attempts to isolate the polar conjugate in pure form were unsuccessful due to its rapid hydrolysis in the presence of acid, and organic solvents such as diethyl ether. Its breakdown product, however, was more stable and was isolated and purified by semi-preparative h.p.l.c. Unequivocal identification as 3-hydroxy-diflunisal (i.e. hydroxylation in position 3 of the salicylic acid ring) was accomplished by means of FAB-mass spectrometry and n.m.r. spectroscopy. 4. The contribution of this oxidative metabolic pathway to the overall elimination scheme of diflunisal is more important in rat than in man. Gunn rats excrete more of the hydroxy diflunisal conjugate in urine (20-30% of a 50 mg/kg i.v. dose of diflunisal) than Wistar rats. In healthy humans, hydroxylation of diflunisal contributes only to a small extent to the overall biotransformation of diflunisal. PMID- 1763527 TI - Absence of phenolic glucuronidation and enhanced hydroxylation of diflunisal in the homozygous Gunn rat. AB - 1. The disposition of diflunisal (DF) was investigated in bile-exteriorized and intact homozygous Gunn rats given 10 and 50 mg/kg doses i.v. and in Wistar rats given 10 mg/kg doses i.v. 2. In Gunn rats, DF sulphate, DF acyl glucuronide, and a hitherto unidentified metabolite of DF, a conjugate of 3-hydroxy-DF, were identified as the major metabolites, accounting for approximately 37%, 16% and 11% respectively of 10 mg/kg doses and 35%, 24% and 15% respectively of 50 mg/kg doses in bile-exteriorized animals. There was no evidence for formation of DF phenolic glucuronide. 3. Total plasma clearance of DF and formation clearances of DF to DF sulphate and 3-hydroxy-DF were little affected by increase of dose from 10 to 50 mg DF/kg, whereas formation clearance of DF to DF acyl glucuronide was increased, but not significantly. 4. In Gunn rats with undisturbed bile flow into the gut, recoveries of DF sulphate and total 3-hydroxy-DF in urine increased to approximately 48% and 25% dose respectively at the expense of DF acyl glucuronide through enterohepatic recirculation. 5. In bile-exteriorized Wistar rats, DF phenolic glucuronide, DF acyl glucuronide, DF sulphate and 3-hydroxy-DF accounted for 16%, 27%, 14% and 2%, respectively, of 10 mg/kg doses. In intact Wistar rats, urinary recoveries of the metabolites were 15%, 13%, 23% and 5%, respectively. 6. Thus in comparison to Wistar rats, phenolic glucuronidation of DF was absent or negligible in homozygous Gunn rats, acyl glucuronidation was significantly decreased, sulphation was unchanged, and the 3-hydroxylation of DF was significantly enhanced. PMID- 1763528 TI - Toxicity of colistin in cystic fibrosis patients. AB - Pulmonary exacerbations of cystic fibrosis associated with strains of Pseudomonas aeruginosa that are resistant to multiple antibiotics are becoming increasingly common. The search for treatment alternatives continues and may include the reexamination of older antibiotics. Colistin sulfate is a polypeptide antibiotic with good activity against P. aeruginosa. Although its use was largely discontinued in the early 1970s because of reports of frequent renal and neurologic toxicity, intravenous colistin is often prescribed at our institution for patients with P. aeruginosa resistant to multiple-drug therapy. We prospectively monitored 19 patients during 21 courses of colistin therapy to identify the character and incidence of this agent's toxicity. Only one case of renal toxicity occurred. Six cases of neurotoxicity occurred, which were characterized by perioral paresthesia, ataxia, or both. The rate of intolerable renal adverse effects secondary to colistin therapy was appreciably lower among these patients than that reported previously for other patients. It appears that intravenous colistin can be considered for cystic fibrosis patients with strains of P. aeruginosa that are resistant to more commonly used antibiotics. PMID- 1763529 TI - Pentamidine-associated nephrotoxicity and hyperkalemia in patients with AIDS. AB - The incidences of pentamidine-associated nephrotoxicity and hyperkalemia were determined from a retrospective review of records in AIDS patients using standard definitions for both toxicities. There were 37 patients, mean age 35.6 +/- 7.7 years and mean initial creatinine clearance (Clcr) 96 mL/min (1.6 mL/s). The mean pentamidine dose was 255 +/- 60 mg/d (3.87 +/- 0.33 mg/kg/d). The mean total dose was 2900 +/- 1600 mg given over 11.6 +/- 5.9 days (range 3-21 d). In 28 patients who were nephrotoxic (8 mild, 6 moderate, 14 severe), 27 episodes were possibly or probably pentamidine-associated. Total dose and days to nephrotoxicity onset were 1570 +/- 710 mg and 6.4 +/- 2.8 days (range 2-15 d), respectively. Nine patients became hyperkalemic (one required countermeasures) and all cases were pentamidine-associated. Total dose and days to hyperkalemia onset were 2510 +/- 1460 mg and 9.2 +/- 4.9 days (range 3-16 d), respectively. Mean baseline potassium increased and Clcr decreased significantly during therapy (from 4.2 to 4.9 mEq/L and from 96 to 70 mL/min, respectively). No correlation between nephrotoxicity or hyperkalemia and initial renal function was found, but significant correlations were found between the total pentamidine dose or duration and the percent of renal function remaining. AIDS patients have a high incidence of pentamidine-associated nephrotoxicity (up to 73 percent) and hyperkalemia (24 percent) with a trend to earlier onset of the former. PMID- 1763530 TI - Amantadine neurotoxicity in a pediatric patient with renal insufficiency. AB - Amantadine hydrochloride, a dopamine agonist with antiviral and antiparkinsonism properties, is used for the prevention and treatment of influenza A respiratory infections in high-risk populations. The occurrence of amantadine-induced hallucinations and tremors is described in a young, renal transplant patient with declining renal function. Following discontinuation of amantadine, plasma amantadine concentrations were correlated with central nervous system toxicity. In view of the usage of amantadine in renal transplant recipients and the elderly, clinicians must be alert to the possibility of amantadine-induced neurotoxicity in patients with changing renal function. PMID- 1763531 TI - Hypotension and bradycardia possibly associated with intraocular injection of acetylcholine. AB - Topically applied drugs are an important part of the pharmacologic management of cataract extraction and lens implant surgery. Acetylcholine facilitates this procedure via its miotic effect on the ciliary body of the eye. Systemic effects can occur with topically administered ophthalmic medications. Acetylcholine has been implicated in several cases of systemic cholinergic effects, such as hypotension, bradycardia, and bronchospasm, following intraocular administration. The patients we present experienced profound hypotension and bradycardia occurring up to 45 minutes after intraocular injection of acetylcholine. Both patients were over 90 years of age and had a history of first-degree atrioventricular block. As cataract surgery and lens implantation become more prevalent in the older ambulatory segment of the geriatric population, healthcare professionals should be aware that these patients may be more sensitive to the pharmacologic effects of medication used during surgery. Monitoring for adverse effects must be performed intraoperatively and several hours postoperatively. Additionally, patients with known conduction abnormalities prior to surgery should be monitored closely and proper emergency equipment and personnel should be available. Pharmacists who investigate adverse drug reactions should consider ophthalmic medications as potential causes for unexplained or suspected adverse drug reactions. PMID- 1763532 TI - Ofloxacin during the second trimester of pregnancy. AB - Ofloxacin can cause retarded ossification and arthropathy in young animals, but there is no published information about its teratogenicity in humans. A 36-year old woman was treated with ofloxacin 200 mg bid for 6 days during the 19th week of gestation. Ultrasound follow-up of the measurements and structure of the fetal long bones revealed no abnormalities. The neonate's physical examination and X rays of the chest and long bones were normal. Although no teratogenic or toxic effects were observed in this patient, the use of ofloxacin in human pregnancy should only be a clinical consideration until sufficient evidence regarding its safety in the human fetus has been published. PMID- 1763533 TI - Naproxen-induced recurrent aseptic meningitis. AB - Aseptic meningitis has been linked to treatment with several nonsteroidal antiinflammatory drugs (e.g., ibuprofen, tolmetin, sulindac), particularly in patients with disturbed immunity. Naproxen, however, has only once been reported to cause meningitis. We report a case of recurrent aseptic meningitis related to prolonged naproxen usage in a 38-year-old woman with longstanding, minimally symptomatic systemic lupus erythematosus (SLE). Two years after starting naproxen, she experienced three separate episodes of meningitis within a period of 10 months; each episode was preceded by resumption of naproxen administration or an increase in drug dosage. There was no clinical or serologic evidence for the flare-ups of her SLE. Discontinuation of naproxen was followed by prompt recovery once the relationship of the drug to her symptoms was realized. Off the drug, the patient has remained free of meningeal symptoms for more than 18 months. Nonsteroidal antiinflammatory agents should be considered as possible causal agents in evaluating meningitis of obscure etiology. PMID- 1763534 TI - Calcitonin in migraine. PMID- 1763535 TI - Talc in the treatment of malignant pleural effusion. PMID- 1763536 TI - Warfarin and the international normalized ratio: reducing interlaboratory effects. AB - In North America, the dose of warfarin has been unintentionally increased during the past two decades because of failure to recognize the effect on the anticoagulation test of less sensitive tissue thromboplastins. Although there still is some controversy, the suggested dose of warfarin has now been adjusted downward to reduce the risk of bleeding. These revised dosing recommendations incorporate the international normalized ratio (INR), which takes into account the source of thromboplastin. However, there is considerable variability in the sensitivities of thromboplastin from manufacturer to manufacturer and lot to lot. Therefore, prothrombin times (PTs) are not comparable from laboratory to laboratory without knowing the sensitivity of the thromboplastin. Unless laboratories adopt a standardized tissue thromboplastin, the PT should be reported as an INR. PMID- 1763537 TI - Felodipine: a new dihydropyridine calcium-channel antagonist. AB - Felodipine, a dihydropyridine calcium-channel antagonist, significantly reduces systolic and diastolic blood pressure (BP) in patients with hypertension and has been associated with beneficial hemodynamic effects in patients with chronic stable angina pectoris or congestive heart failure (CHF). In hypertensive patients, felodipine does not appear to significantly affect glomerular filtration rate, creatinine clearance, glucose tolerance, or plasma lipoprotein concentrations. Studies comparing felodipine with other agents as monotherapy in mild to moderate hypertension have demonstrated felodipine to be at least as efficacious as hydrochlorothiazide (HCTZ) and HCTZ plus amiloride hydrochloride in combination. Comparisons of felodipine with other agents as adjuncts to beta blocker or diuretic therapy have shown felodipine to be at least as effective as HCTZ, propranolol hydrochloride, prazosin hydrochloride, and nifedipine. Evaluations of patients with chronic stable angina are limited, and additional studies are needed before felodipine can be recommended for the routine management of angina pectoris. Similarly, additional studies are essential to delineate the role of felodipine, if any, in the management of CHF. In the management of hypertension, felodipine 5-40 mg/d significantly reduces systolic and diastolic BP. Although some patients may be controlled throughout the entire dosing interval when felodipine is administered bid, many patients will require more frequent dosing to obtain adequate BP control. Adverse effects associated with felodipine are similar to those of other dihydropyridine calcium-channel antagonists and include peripheral edema, headache, dizziness, flushing, and fatigue. A potentially clinically important drug interaction was observed when felodipine was administered concomitantly with theophylline aminopropanol; significant decreases in theophylline concentrations were noted. In summary, felodipine appears to be safe and effective for the management of hypertension when used alone or in combination with other antihypertensive agents. The efficacy of felodipine in the management of chronic stable angina pectoris and CHF requires further investigation. PMID- 1763538 TI - Treatment of attention deficit hyperactivity disorder: a critical review. AB - This review evaluates the treatment of attention deficit hyperactivity disorder. Current evidence supports the belief that stimulants are the most effective and least toxic of the drugs used in the treatment of hyperactivity. Tricyclic antidepressants (TCAs), however, are preferable in subpopulations with concomitant anxiety or depressive disorders. Studies comparing stimulants with TCAs are evaluated and studies that have examined other antidepressants are summarized. In addition, TCAs and stimulants are compared according to adverse effect profiles, pharmacokinetic properties, and subgroup responses. Based on these data and the recently reported sudden deaths in children receiving desipramine, treatment recommendations are made. PMID- 1763539 TI - The effect of renal failure on hepatic drug clearance. AB - It is known that loss of renal function decreases the hepatic clearance of some drugs, but the mechanisms by which this occurs are unclear. Knowledge of which drugs display reduced hepatic metabolism may be important for appropriate dosing of these drugs in uremic patients. Although no firm conclusions can be made regarding common pharmacokinetic and metabolic characteristics of drugs that display decreased hepatic metabolism in renal failure, certain observations deserve consideration. It appears that drugs metabolized by oxidation, conjugation, or both may be predisposed to decreased hepatic clearance in renal failure. Drugs that undergo oxidation by the P-450IID6 isozyme may be more likely to exhibit inhibition whereas those metabolized by the P-450IIIA4 isozyme may be spared. Future studies designed to clarify the mechanisms of decreased hepatic clearance in renal failure should take into account the multiplicity of P-450 enzymes for drugs that are oxidatively metabolized. The phenomenon of reduced hepatic drug clearance in uremia should be considered when evaluating the influence of renal failure on drug disposition. PMID- 1763540 TI - Charge and reimbursement analysis for intensive care unit patients in a large tertiary teaching hospital. AB - Hospital charge and reimbursement data were analyzed for 115 patients admitted to the surgical intensive care and burn-trauma units at Brigham and Women's Hospital over a two-month study period. A skewed distribution of hospital charges resulted in mean and median charges of $43,068 and $29,081, respectively. Major differences were observed in total charges among major diagnostic groups. The median charge was highest in orthopedic trauma and neurosurgery patients. The median charge across major diagnostic groups correlated with the length of stay in the unit and in the hospital, and the number of drugs used. The median percent reimbursement from private providers, Medicaid, Medicare, and health maintenance organizations was 93, 55, 40, and 30 percent, respectively, and 55 percent overall. Reimbursement was high from private providers regardless of major diagnostic group. Medicare reimbursement through the diagnostic reference group system was considerably higher in cardiothoracic patients (77 percent) than in other major diagnostic groups. The discrepancy between charge and Medicare reimbursement in these patients was consistent with that reported for intensive care units in other hospitals, thereby underscoring the need for cost containment and more realistic reimbursement methods. PMID- 1763541 TI - The safety, efficacy, and tolerability of cefuroxime axetil suspension in infants and children receiving previous intravenous antibiotic therapy. AB - The tolerability, safety, and efficacy of cefuroxime axetil suspension was studied in 36 children (aged 3 mo to 12 y) who had been hospitalized for respiratory tract or soft-tissue infections. After receiving parenteral antibiotics for a mean of 3.7 days, children were discharged home to receive cefuroxime axetil suspension at doses of 10, 15, or 20 mg/kg every 8 or 12 hours for a mean of 8.2 days. One child was lost to follow-up. Three of 35 evaluated patients were withdrawn from therapy because of adverse events, one of which was a drug-related hypersensitivity reaction. Of the 32 children who completed therapy, 9 developed mild reactions including oral thrush, diarrhea, or diaper dermatitis; none were withdrawn from therapy. Complete clinical cure occurred in 28 children (80 percent); 4 (11.4 percent) were clinically improved but still required an additional antibiotic within one week of completing therapy with cefuroxime axetil suspension. This favorable tolerability and safety of cefuroxime axetil suspension warrants further efficacy trials in pediatric patients. PMID- 1763542 TI - Quinolone-cation interactions: a review. AB - The quinolone class of antibiotics is enjoying a recent resurgence in interest and use due to the development of improved compounds. Norfloxacin, ciprofloxacin, and, most recently, ofloxacin have been marketed. Enoxacin and other agents are in various stages of investigation. These newer compounds are often used for indications not successfully treated by the original quinolones, or in some cases, not optimally treated with any previously available oral antibiotic. A potential problem with the increasing use of quinolone-type antibiotics for systemic illness is the chelation and inactivation of these compounds by several cations. One outcome of these potential interactions is a possible reduction in bioavailability and effectiveness of quinolone compounds. A review of the literature on quinolone-cation interactions, in vivo and in vitro significance, and recommendations to avoid potential problems are provided. PMID- 1763543 TI - Tryptophan toxicity: a pharmacoepidemiologic review of eosinophilia-myalgia syndrome. AB - Tryptophan, an essential amino acid commercially available as a dietary supplement, has been implicated in the development of a new and potentially fatal clinical entity: eosinophilia-myalgia syndrome (EMS). EMS reached epidemic proportions in the US in late 1989 and early 1990, with 1536 cases and 27 deaths reported as of August 1990. Features of the syndrome include intense, debilitating myalgias and marked peripheral eosinophilia. Vasculitis, neuropathy, and pulmonary involvement also may be observed but are not pathognomonic. Death typically ensues from ascending polyneuropathy with resulting paralysis and respiratory arrest. Treatment involves discontinuation of tryptophan ingestion. Administration of prednisone may not always alleviate or reverse the symptoms. Recovery is generally slow. The etiology of EMS has been traced to a contaminant in the bulk manufacturing process of tryptophan by a single Japanese company. Efforts are currently underway to confirm the structure of the contaminant by laboratory synthesis and to define its biologic and toxic effects using an animal model for EMS.